Iranian Journal of Pharmaceutical Research
Volume:22 Issue: 1, Winter 2023

 Naringenin (Nar) has anti-inflammatory and anticarcinogenic properties. Arginine-glycine- aspartate (RGD) is a tripeptidic sequence used as an integrin ligand and targeting system for delivering chemotherapeutic agents to cancer cells.

 In this study, the inhibitory effects of Nar and ketoprofen-RGD on leukemia and ovarian cancer cells (K562 and SKOV3) were explored for the first time, focusing on their proliferation activity and their anti-inflammatory capacity.

 Analyses were conducted on the calmodulin (CaM)-dependent phosphodiesterase 1 (PDE1) activation by ketoprofen-RGD, Nar, and their combination. These drugs’ effects on protein kinase A (PKA) activation, intracellular cyclic adenosine monophosphate (cAMP) level, and PDE1 inhibition were identified. Later, it was also evaluated if ketoprofen-RGD alone or in combination with Nar had anti-inflammatory effects.

 Nar improved the antagonizing consequences of ketoprofen-RGD on the CaM protein, which hinders PDE1, improving PKA activity and cAMP levels. A mixture of ketoprofen-RGD and Nar and ketoprofen-RGD alone diminished K562 and SKOV3 cell viability through the cAMP/PKA pathway by inhibiting PDE1 and CaM. These two compounds showed anti-inflammatory effects on both cell lines.

 This study indicated for the first time that combining ketoprofen-RGD and Nar can be a promising anti-inflammatory therapeutic regimen for treating leukemia and ovarian cancer.

 The prevalence of obesity has almost tripled since 1975, and obesity places a heavy economic burden on healthcare systems. There is a high tendency to use a variety of complementary medicine modalities for weight management among obese patients. Persian Medicine is an ancient medical school practiced for thousands of years in Iran. Found in reliable Iranian traditional resources, Komouni formulation (KF) is a compound medicine that can be effective in the treatment of obesity. It comprises black caraway (Bunium persicum Boiss.), anise (Pimpinella anisum L.), fennel (Foeniculum vulgare Miller), and ajwain (Trachyspemum ammi L.)

 This study aimed to determine the effects of KF on anthropometric indices and metabolic parameters in overweight and obese women.

 This triple-blinded randomized controlled clinical trial was performed on 70 overweight or obese women aged 20 - 40 years, with a body mass index (BMI) of 25 - 34.9 kg/m2. The subjects were randomly divided into two groups (each group n = 35) to receive a calorie-restricted diet with 2 g/day (500 mg 30 minutes before breakfast, 1000 mg 30 minutes before lunch, and 500 mg 30 minutes before dinner) KF or placebo for 8 weeks. Anthropometric indices, food intake, and biochemical parameters were measured at baseline and after the intervention.

 A total of 60 women (intervention = 30; placebo = 30) completed the trial. After the intervention, the KF group experienced a significant reduction in weight (-4.8 vs. -3.2 kg; P = 0.0001), BMI (-1.8 vs. -0.79 kg/m2; P = 0.0001), waist circumference (-5.28 vs. -3.20 cm; P = 0.004), hip circumference (-0.018 vs. -0.008 cm; P = 0.047), fasting blood sugar (-5.6 vs. 0.33; P = 0.025), and low-density lipoprotein (-11.7 vs. 6.7; P = 0.0001), compared to the placebo group. None of the patients in the intervention and placebo groups reported any side effects.

 Using KF, along with a calorie-restricted diet, can reduce cardiometabolic risk factors in overweight and obese women. However, further studies are needed to elucidate the efficacy of KF as a complementary therapy in obesity.

 The stratum corneum (SC) serves as the primary barrier for permeation in human skin. Penetration enhancers, such as 1,8-cineole, are utilized to enhance the permeation of drugs. Cineole increases the permeation of chemicals through different mechanisms. However, its mechanism, particularly at high concentrations, has not been well-studied and is the subject of the present investigation.

 In continuation of our previous studies, the present investigation aims to elucidate the mechanism of action and concentration dependency of the effects of 1,8-cineole on the structure, diffusional properties, and partitioning behavior of the SC at high concentrations. This will be achieved through lamellar liquid crystalline models and ex-vivo skin studies.

 A lamellar liquid crystalline lipid matrix model in the presence (25 - 90%, w/w) and absence of cineole was prepared from SC lipids and characterized by X-ray diffraction, differential scanning calorimetry (DSC), Thermogravimetric Analysis (TGA), and Polarized Light Microscopy (PLM) studies. The release of the model lipophilic drug (diazepam) from cineole and cineole-treated matrices and the permeation of the drug from cineole and cineole-containing matrices (as a vehicle similar to the stratum corneum lipids) through excised rat skin were studied. A drug assay was performed by HPLC.

 The PLM, DSC, and X-ray studies showed that the model matrix had a lamellar gel-liquid crystalline structure, and cineole fluidized the structure concentration dependently and created other mesomorphic textures, such as myelinic figures. Release experiments showed that diffusion coefficients remained almost constant at high cineole concentrations of 40-90%, suggesting similar fluidization states. Skin permeation studies indicated that the diffusion coefficient (estimated from lag-time) increased concentration-dependently and played a role in permeability coefficient (Kp) increments alongside the increased partitioning of the model drug into the skin. Data suggest that high concentrations of cineole at the skin surface might not provide enough cineole in the skin for full fluidization, despite the similarity of the vehicle to SC lipids and even at high concentrations.

 The enhancement effect of cineole is concentration-dependent and might reach maximum fluidization at certain concentrations, but this maximum might not be easily achievable when cineole is used in formulations as pure or in a vehicle.

Expression of the miR-34 family, including miR-34a/b/c, has been reported to inhibit the progression of several cancer types by inhibiting cell proliferation and inducing apoptosis.

Therefore, we attempted to investigate the effect of SW480 cell transfection with miR-34c-5p mimics on cell proliferation.

To do this, SW480 colon cancer cell line was transfected with miR-34c-5p mimics, scramble sequence, and the vehicle in PBS mock, and then cell proliferation was assessed by MTT assay. The population of cells in cell cycle phases, ROS generation, and apoptosis rate were evaluated by flow cytometry. Additionally, we determined the relative expression of apoptotic genes through real-time PCR technique.

We observed a reduced proliferation rate in cells transfected with miR-34c-5p compared to the control group (P <0.05). We also found that miR-34c-5p caused a significant increase in apoptosis rate (P < 0.001) and cell cycle arrest in the G0 and G1 phases (P < 0.05). Moreover, a significant increase was reported in the expression of pro-apoptotic genes, including BAK (P < 0.001), BAX and BAD (P < 0.0001), and CASPASE 7/9 (P < 0.0001).

However, no remarkable difference was seen in the expression of MCL1, BCL2, and CASPASE 3 genes. Our conclusion is that overexpression of miR-34c-5p could be considered a promising approach for colorectal cancer treatment.

 Given the intensifying competition, adapting to the market environment and meeting customer demands are crucial aspects of the evolving marketing process. Market orientation (MO) represents an organizational culture encompassing shared beliefs and values that prioritize the customer's role in business planning.

 This study seeks to explore the impact of MO on innovative performance (IP) and the potential mediating role of dynamic capabilities (DC) and corporate social responsibility (CSR) in this relationship.

 For this study, a structured quantitative questionnaire was distributed to 100 local pharmaceutical companies, resulting in 300 completed questionnaires. Each questionnaire consisted of four main components, which were filled out by three managers from each company: Chief executive officer (CEO), marketing manager, and research and development manager. The collected data were analyzed using SPSS software and structural equation methods to examine the research questions and hypotheses.

 According to the study findings, there was a positive correlation between employee age, organizational structure, sales volume, and the presence of private companies with IP. MO, DC, and CSR showed a direct and significant relationship with IP. Moreover, the CSR of the company influenced IP through the mediating role of DC. Market orientation was found to enhance explorative IP, leading to improvements in existing processes and services.

 Based on the study results, it was found that MO has a direct positive impact on IP, leading to improvements in the company's existing processes through its influence on exploratory performance.

 Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are 2 common liver diseases that currently lack effective treatment options.

 This study aimed to investigate the effect of lipopolysaccharide (LPS)-stimulated adipose-derived stem cells (ADSCs) on NAFLD treatment in an animal model.

 Male Wistar rats were fed a high-fat diet (HFD) to induce NAFLD for 7 weeks. The rats were then categorized into 3 groups: Mesenchymal stem cell (MSC), MSC + LPS, and fenofibrate (FENO) groups. Liver and body weight were measured, and the expression of genes involved in fatty acid biosynthesis, β-oxidation, and inflammatory responses was assessed.

 Lipopolysaccharide-stimulated ADSCs were more effective in regulating liver and body weight gain and reducing liver triglyceride (TG) levels compared to the other groups. Treatment with LPS-stimulated ADSCs effectively corrected liver enzymes, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and lipid factors, including low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) values, better than treatment with both FENO and MSCs. ADSCs + LPS treatment significantly decreased transforming growth factor β (TGF-β) and genes associated with inflammatory responses. Additionally, there was a significant reduction in reactive oxygen species (ROS) levels in the rats treated with ADSCs + LPS.

 Lipopolysaccharide-stimulated ADSCs showed potential in alleviating NAFLD by reducing inflammatory genes and ROS levels in HFD rats, demonstrating better results than treatment with ADSCs and FENO groups alone.

 Malignant tumors are a significant disease endangering human health. Chinese Medicine (CM) plays an important role in comprehensive and holistic tumor treatment.

 We aimed to investigate whether CM combined with the immunosuppressant PD-1/PD-L1 inhibitor has a good synergistic effect and can significantly improve response rates for the immunosuppressant.

 We combined CM with immunosuppressant in treating six-week-old hepatocellular carcinoma-bearing mice and compared the outcomes of groups undergoing different interventions: blank group, control group, CM group, PD-L1 inhibitor group, and CM + PD-L1 inhibitor group, with ten mice in each group. The quality of life was evaluated along with the tumor inhibition effects and growth rates.

 CM significantly reduced tumor load and improved the quality of life of cancer-bearing mice. The survival rate was 81.8% in the control group, 100% in the CM group, 90.9% in the PD-L1 inhibitor group, and 100% in the combined group in the first week. The survival rate was 45.5% in the control group, 54.5% in the CM group, 81.8% in the PD-L1 inhibitor group, and 81.8% in the combined group in the second week. 38% mice in the CM+PD-L1 inhibitor group with smaller tumor size than the average of the control group, which was much higher than other treatment groups. CM also reduced the expression of JAK2 mRNA and STAT3 mRNA, although not significantly (P > 0.05), and reduced PD-L1 mRNA in tumor tissue compared to the control group (P < 0.05).

 CM had a synergistic effect on PD-L1 inhibitors and increased response rates to PD-L1 inhibitor treatment.

Context:

 Fungal infections are very common, and several medications are used to treat them. Azoles are prescribed widely to treat fungal infections. In addition to therapeutic effects, any drug can be accompanied by side effects in patients. One of the most important complications in this regard is liver injury. Therefore, hepatotoxicity induced by azole antifungal drugs were reviewed in this study.

Evidence Acquisition:

 English scientific papers were evaluated to review the effects of hepatotoxicity by azole antifungal agents, and the related studies' results were summarized using a table. The systematic search was implemented on electronic databases, including PubMed, Google Scholar, and Science Direct. Original articles and review articles that were published before April 1, 2022, were included in the study. Those articles without available full text or non-English articles were excluded. Also, articles that reported pediatric data were excluded.

Most studies have reported the effects of hepatotoxicity by azole antifungal agents, and their mechanisms have been described.

Clinical evaluations regarding the hepatotoxicity of antifungal agents provided in the literature were reviewed. Therefore, it is recommended to prescribe these drugs with caution in high-risk patients suffering from liver diseases, and patients should be monitored for hepatotoxicity. However, more research is needed to evaluate the hepatotoxicity of azole antifungal agents and select appropriate drugs according to cost-effectiveness and the side effects' profiles, relying on lower incidence of this liver complication.

 Cisplatin-induced nephrotoxicity has been linked to a fundamental mechanism of mitochondrial dysfunction. A treatment called mitochondrial transplantation therapy can be used to replace damaged mitochondria with healthy mitochondria. Mitochondrial-related diseases may benefit from this approach.

 We investigated the effect of mitochondrial transplantation on cisplatin-induced nephrotoxicity using freshly isolated mitochondria obtained from renal proximal tubular cells (RPTCs).

 Based on our previous findings, we hypothesized that direct exposure of healthy mitochondria to cisplatin-affected RPTCs might improve cytotoxicity markers and restore mitochondrial function. Therefore, the primary objective of this study was to determine whether newly isolated mitochondrial transplantation protected RPTCs from cisplatin-induced cytotoxicity. The supply of exogenous rat kidney mitochondria to cisplatin-affected RPTCs was also a goal of this study to investigate the possibility of gender differences. After the addition of cisplatin (100 µM), rat RPTCs (106 cells/mL) were suspended in Earle’s solution (pH = 7.4) at 37°C for two hours. Freshly isolated mitochondria were extracted at 4°C and diluted in 100 and 200 µg/mL mitochondrial protein.

 Statistical analysis revealed that transplantation of healthy mitochondria decreased ROS level, mitochondrial membrane potential (MMP) collapse, MDA level, glutathione depletion, lysosomal membrane damage, and caspase-3 activity induced by cisplatin in rat RPTCs. In addition, our results demonstrated that transplantation of female rat kidney mitochondria has higher protective activity at reducing toxicity parameters than male mitochondria.

 The findings reaffirmed that mitochondrial transplantation is a novel, potential, and promising therapeutic strategy for xenobiotic-induced nephrotoxicity.

 The prevalence of type 2 diabetes mellitus (T2DM) is increasing worldwide, and this issue is one of the major concerns in the pending years. T2DM causes numerous complications, including cognition, learning, and memory impairments. The positive effect of physical exercise as a popular approach has been shown in many chronic diseases. Further, the improvement effects of exercise on cognition and memory impairment have been noticed.

 This study examines the possible preventative effects of physical exercise on spatial memory attenuation and brain mitochondrial dysfunction caused by T2DM.

 Male Wistar rats received treadmill exercise (30 min per day, five days per week for two or four weeks). Then, T2DM was induced by a high-fat diet and an injection of streptozotocin (30 mg/kg). Spatial learning and memory were assessed by the Morris water maze test. Further, brain mitochondrial function, including reactive oxygen species (ROS) generation, mitochondrial membrane potential (MMP), mitochondrial swelling, outer membrane damage, cytochrome c release, and ADP/ATP ratio, were measured.

 Impaired spatial memory in T2DM rats was observed. Furthermore, brain mitochondrial dysfunction was demonstrated proved by increased ROS generation, MMP collapse, mitochondrial swelling, outer membrane damage, cytochrome c release, and ADP/ATP ratio. Conversely, physical exercise, before diabetes onset, significantly ameliorated spatial memory impairment and brain mitochondrial dysfunction.

 This study reveals that physical exercise could prevent diabetes-induced spatial memory impairment. Moreover, it could ameliorate brain mitochondrial dysfunction as one of the possible underlying mechanisms of spatial memory impairment in T2DM.

 Community pharmacists play an important role in improving outcome by providing advice and counselling services to patients.

 The aim of this study was to measure the willingness to pay (WTP) for pharmacist counselling services in community pharmacies and identify determinant factors on consumers’ WTP.

 A self-administered questionnaire-based survey was conducted in community pharmacies in Tehran (capital of Iran) from January 1, 2020 to February 20, 2021. Contingent valuation method was applied to evaluate respondents’ maximum WTP using three hypothetical scenarios illustrating different levels of counselling services. Logistic regression was used to analyze the association between different variables and WTP for pharmacy services.

 Total number of participants who completed the questionnaire were 332 and 60% of the participants were male. In the first scenario 70.2% of participants were willing to pay for oral counselling pharmacy services. In the second and third scenario, percentage of people willing to pay increased to 79.5%. and 86.1%, respectively. In the first scenario, monthly income (OR = 0.041, P value = 0.04), the duration of underlying illness (OR = 0.04, P value = 0.04) and the using internet (OR = 2.59, P value = 2.59) had a statistically significant relationship with willingness to pay. In the third scenario, the willingness to pay increased as the age decreased. The possibility of using the internet (OR = 3.32, P value = 0.00) and the need for a community pharmacist (OR = 2.19, P value = 0.03) increased the chance of willingness to pay.

 More consumers are willing to pay for more pharmacist counselling services. Therefore, improving the quality of counselling services could have positive economic effects on community pharmacies.

 Cisplatin has potent antitumor properties. It has several toxic side effects, such as hepatotoxicity. It is thought that hepatotoxicity induced by cisplatin is caused by oxidative stress.

 It has shown that calcium dobesilate (CD) has potent antioxidant properties. The present study aimed to assess CD protective effects on cisplatin-induced hepatotoxicity in mice.

 In this study, 28 mice were selected randomly and were divided into four groups, including control, cisplatin (20 mg/kg, i.p., only on the first day of the experiment), Cisplatin+CD 50 (50 mg/kg CD, orally), and Cisplatin+CD 100 (cisplatin with 100 mg/kg CD, orally). A 4-day oral gavage of CD was applied to the treated groups. The mice were sacrificed on the 5th day, and serum glutamic pyruvic transaminase (SGPT), serum glutamic-oxaloacetic transaminase (SGOT), alkaline phosphatase (ALP), malondialdehyde (MDA) and reactive oxygen species (ROS) levels, superoxide dismutase (SOD), and glutathione peroxidase (GPx) enzyme activity levels in liver tissue were evaluated. Histopathological evaluation was assessed using hematoxylin and eosin-stained liver tissue sections.

 The results indicated that there was a significant increase in GSPT, SGOT, ALP, and MDA and also a significant reduction in the liver activity of SOD and GPx in cisplatin-treated animals. Treatment with CD (100 mg/kg) remarkably attenuated the GSPT, SGOT, ALP, MDA, and ROS levels. Moreover, CD (100 mg/kg) elevated the SOD and GPx activity in the liver tissue of cisplatin-treated mice.

 The findings showed that CD has a protective effect against cisplatin-induced hepatotoxicity, at least by improving the antioxidant parameters.

 In recent decades, algae have attracted worldwide attention for their great biological activities, such as antidiabetic and antibacterial properties.

 We measured antibacterial and α-glucosidase inhibition potential of methanol and 80% methanol extracts of three brown algae species, Polycladia myrica, Padina antillarum, and Sargassum boveanum, and a red alga, Palisada perforata, from the Persian Gulf coasts.

 Antibacterial activity of the algal extracts was assessed by broth dilution method against three gram-negative and -positive bacteria, including Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa; Staphylococcus epidermidis, Staphylococcus aureus, and Bacillus subtilis, respectively. Furthermore, the yeast’s α-glucosidase inhibition of the algal extracts was measured via colorimetric assay. In addition, we investigated the beneficial effect of 80% MeOH extract of S. boveanum on the blood glucose levels in streptozotocin-induced diabetic rats.

 The MeOH extract of S. boveanum was the best antibacterial extract with MIC = 2.5 mg/mL against all bacterial strains except for E. coli. The MeOH and 80% MeOH extracts of P. myrica and P. antillarum inhibited α-glucosidase at most with IC50 values of 12.70 ± 1.88 µg/mL and 13.06 ± 4.44 µg/mL, respectively. The oral gavage of S. boveanum extract in streptozotocin- (STZ-) induced diabetic rats resulted in decreasing their postprandial blood glucose levels. The algae and acarbose decreased blood glucose levels after sucrose administration in 60 minutes, compared to the non-drug-treated animals, with p values of 0.03 and 0.007, respectively.

 Overall, due to the in vitro and in vivo antidiabetic potential of S. boveanum, we suggest the alga as a new source for the isolation and identification of potential antidiabetic and antibacterial compounds.

Breast cancer is a deadly disease with a high prevalence rate among females. Despite several treatments, scientists are still engaged in finding less invasive treatments for this disease. The cellular proliferation rate and cell viability survey are critical to assess the drug’s effect on both normal and malignant cell populations. Indole derivatives are promising candidates for their cytotoxic effect causing on breast cancer cells; however, they are less toxic on normal cells. This study synthesized 23 novel 5-hydroxyindole-3-carboxylic acids and related esters featuring various linear, cyclic, and primary aromatic amines. The MTT assay indicated the cytotoxicity of all acid and ester derivatives against the MCF-7 cells with no significant cytotoxicity on normal human dermal fibroblasts cells. Compound 5d, an ester derivative possessing a 4-methoxy group, was the most potent compound, with a half-maximal effective concentration of 4.7 µM. Compounds 5a, 5d, and 5l bearing ester group in their structure demonstrated cytotoxicity values < 10 µM against the MCF-7 cell line and were safe for advanced screening.

 Chromene derivatives showed numerous biological activities. In the current study, the antioxidant, cytotoxicity, and apoptosis properties of halogenated dihydropyrano[3,2-b]chromene-3-carbonitrile derivatives (HDCCD) on MCF-7 cell line have been examined.

 This study's principal point was synthesizing new halogenated pyranochromene derivatives and assessing their cytotoxic effects and apoptosis potential on MCF-7 breast cancer cell line by flow cytometry.

 Initially, 6-chloro- and 6-bromo-3-hydroxychromone compounds were prepared. In the next step, a series of HDCCD were synthesized by a one-pot three-component reaction of these two compounds, aromatic aldehydes, and malononitrile, in the presence of triethylamine in EtOH at reflux conditions. These compounds were fully characterized by standard spectroscopic techniques (IR, 1H, and 13C NMR) and elemental analyses. The potential of the antioxidant activity was determined by using ferric reducing antioxidant power assay (FRAP). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) were used to evaluate metabolic activity. The nitric oxide (NO) and malondialdehyde (MDA) biomarkers of the exposed cells were evaluated on the cells and their supernatant. To quantify apoptotic death of MCF-7 breast cancer cells treated by the compounds at their IC50 concentrations, Annexin V-FITC apoptosis detection kit was utilized. Molecular docking of compounds (6a-j) into the Cyclin-dependent kinase 6 (PDB code: 4EZ5) was carried out, and the probable binding mode of compounds 6e and 6j was determined.

 A dose-response relationship was seen in all the compounds. Most of them induced cytotoxic effects on the cells. Nitrite concentration of the culture media of the cells was decreased compared to the control. Malondialdehyde levels of the cells were below the range of the control by the addition of 6b, 6d, 6e, 6f, and 6g compounds on the cells, while the addition of the 6a, 6c, 6h, 6i, and 6j compounds increased the MDA level compared to the control. Flow cytometric analysis showed that most of the exposed cells were in the early and late apoptotic stage, and a few of them were in the necrotic stage.

 It could be concluded that HDCCD (6a-j) was toxic and caused death in the cells by apoptosis. The compounds have lipophilic characteristics, so they can easily pass the cell membrane. As confirmed by LDH results, it can be concluded that the cytotoxicity is connected with apoptosis rather than necrosis, endorsed by flowcytometry analysis afterward.

 Breast cancer is a multifaceted disease characterized by genetic and epigenetic changes that lead to uncontrolled cell growth and metastasis. Early detection and treatment are crucial for managing diseases.

 The objective of this study is to investigate the potential of chimeric peptides for drug delivery and to identify biomarkers associated with breast cancer. Recent studies have shown that the low-density lipoprotein receptor-related protein 1 (LRP-1) receptor has a significant impact on the development of breast cancer. In order to facilitate the identification of biomarkers, we have created a chimeric peptide that has been proven to bind successfully to the LRP-1 receptor.

 To identify biomarkers, we utilized advanced computational methods to conduct a meta-analysis of microarray data. Specifically, the g:Profiler and eXpression2Kinases (X2K) databases were utilized to identify gene ontologies and transcription factors. We then used the Human Protein Atlas to identify and assess crucial gene expressions.

 Our results demonstrated that nucleolar and spindle-associated protein 1 (NUSAP1), melatonin receptor 1A (MELT), and cyclin-dependent kinase 1 (CDK1) are three hub genes that play pivotal roles in the pathogenesis of breast cancer.

 The research findings provide a deeper understanding of the molecular mechanisms involved in developing breast cancer. These findings have significant implications for developing novel therapies and diagnostics for this disease.

Polyamines prolong longevity due to their role in cell proliferation and are regarded as an essential group of anti-aging substances that reduce the risk of cardiovascular, neurological, and chronic inflammatory illnesses, as well as cancer. Because of its importance in growth and tissue regeneration, discovering polyamine-rich sources has gotten a lot of interest. Given the role of polyamines in controlling plant growth and physiological changes in the spring after cold winter stress, high polyamine concentrations in quickly growing plant tissues such as flowers, blossoms, and germs are possible. Based on this premise, five different spring flowers were selected and isolated from relevant plants, dried, and then quantified for the first time using an accurate, simple, and repeatable quantification method, liquid chromatography–tandem mass spectrometry. According to the amount of spermidine found in the samples investigated in this study, dried flower powders of Wisteria sinensis (244.18 µg/g), Lonicera caprifolium (217.28 µg/g), and Jasminum officinale (200.33 µg/g) appear to be a good source of spermidine. With additional research, W. sinensis dried flower powder is a good source of polyamines, whereas L. caprifolium and J. officinale dried flower powders are recommended as a rich source of spermidine for the preparation of natural supplements for people over the age of 30 to improve cell proliferation and anti-aging.

Non-alcoholic fatty liver disease (NAFLD) incidence and prevalence are rapidly increasing globally. The combined effects of metformin and quercetin (Que) have yet to be investigated. However, both have demonstrated the potential to reduce triglyceride (TG) levels and treat NAFLD by promoting autophagy. The objective of the present study was to elucidate the mechanism of action and assess the role of autophagy in the lipid-lowering effects of Que, both individually and in combination with metformin, in a HepG2 cell model of hepatic steatosis. Triglyceride levels and lipogenic gene expression were reduced in HepG2 cells exposed to palmitic acid (PA) when treated with Que-metformin, as evidenced by triglyceride measurements and real-time PCR. The LDH release assay also showed that this combination induced autophagy to protect HepG2 cells from PA-induced cell death. According to the Western blot analysis outcomes, Que-metformin increased LC3-I and LC3-II protein levels while decreasing p62 expression to induce autophagy. In HepG2 cells, the co-administration of Que-metformin elevated cAMP, phosphorylated AMP-activated protein kinase (p-AMPK), and Beclin-1 levels. Additionally, the inhibition of SIRT1 reversed the autophagy induced by Que-metformin. The findings of this study demonstrated for the first time that Que-metformin reduced hepatosteatosis by stimulating autophagy through the cAMP/AMPK/SIRT1 signaling pathway and diminishing inflammatory cytokines.

 Chemotherapy drugs can cause drug resistance and other problems when treating lung cancer, which leads to treatment failure. Ursolic acid (UA) is used in formulations based on traditional Chinese medicine. UA has excellent anti-tumor effects, but they are limited by solubility and non-specificity to tumor cells.

 To overcome these issues, we created a novel hyaluronic acid (HA)-targeted liposome system for delivering UA (HA-Lipo/UA) to explore the targeting and anti-tumor effects of UA.

 We constructed the HA-Lipo/UA delivery system by the thin film hydration method. The uptake and localization of UA were detected by flow cytometry and microscope. Cell proliferation of A549 cells was detected by MTT assays. Apoptosis and reactive oxygen species (ROS) expression of A549 cells were also evaluated after being treated with HA-Lipo/UA. Western blot analysis evaluated the anti-tumor mechanism of HA-Lipo/UA.

 HA-Lipo/UA exhibited favorable targeting of the cluster of differentiation (CD)44-overexpressing A549 cells. HA-Lipo/UA exhibited significant inhibition of the proliferation of A549 cells and induced their apoptosis compared with the corresponding monotherapies. HA-Lipo/UA induced overexpression of reactive oxygen species and upregulated expression of p53 and apoptosis-related protein in the transforming growth factor-β signaling (ARTS) pathway, which induced cytochrome-c release, activation of caspase-3, and promoted mitochondrial apoptosis in A549 cells.

 Taken together, these data suggested that HA-Lipo/UA could be used to target tumor cells.

 Amphotericin B (AmB) is the first-line drug to treat invasive fungal infections. However, its delivery to the body and clinical use faces many challenges because of its poor solubility, poor pharmacokinetics, and severe nephrotoxicity.

 Due to the necessity for designing safer and more effective nanocarriers for AmB and the importance of preclinical pharmacokinetic studies in evaluating these novel drug delivery systems, the present study was framed to explore the influence of rat strain on the pharmacokinetic profile of this drug.

 Twenty-four Wistar and Sprague–Dawley (SD) rats were intravenously injected with 1 mg/kg AmB as Fungizone or AmBisome, which are the two most commonly marketed formulations of the drug. Blood samples were collected before and at regular intervals up to 24 h after administration. Drug concentration was analyzed by a validated HPLC method, and pharmacokinetic parameters were determined by the non-compartmental method.

 Irrespective of the type of formulation, the AUC0-t and AUC0-∞ values were significantly higher (P < 0.001), and Cl as an important PK parameter was markedly lower (P < 0.001) in SD rats compared to the Wistar strain. For Fungizone, the mean Cl values in SD and Wistar rats were 206.90 and 462.95 mL/h/kg (P < 0.001), respectively. The apparent volume of distribution (Vss) was also lower in SD rats compared to Wistar; however, for AmBisome, the difference in Vss was not statistically significant. Our further investigation suggested that the higher amount of total protein in the SD strain may justify the higher plasma concentrations and lower Cl and Vss of amphotericin B in this strain compared to the Wistar strain.

 Overall, following intravenous administration of AmB, there were significant differences in the pharmacokinetic parameters of the drug between two rat strains for both formulations. The obtained data is important for correctly interpreting experimental data from different research groups.

 Periodontitis is a chronic disease characterized by the inflammation of the periodontium and leads to progressive damage, such as gingival atrophy, alveolar bone loss, and tooth loss. Streptococcus mutans and Aggregatibacter actinomycetemcomitans are bacteria that support the occurrence of periodontitis via the ability to form biofilms or damage the alveolar bone and periodontal ligaments. On the other hand, periodontal ligament stem cells (PDLSCs) are cells with differentiation capability into osteoblasts or osteoblasts. Due to their role in periodontal homeostasis and regeneration, PDLSCs are considered to control periodontitis progression. However, probiotics are helpful microorganisms known to have antimicrobial and immune-regulating effects.

 This study aimed to evaluate the antioxidant activity and antimicrobial effects of lyophilized cell-free supernatants (LCFSs) derived from three probiotic strains of Lactobacillus on S. mutans and A. actinomycetemcomitans. Moreover, the effect of these lyophilized supernatants was investigated on the viability and migration capability of PDLSCs.

 The antibacterial effects of LCFSs of three probiotic bacteria were investigated by determining the minimum inhibitory concentration and minimum bactericidal concentration. Then, the effect of LCFSs on the survival and migration of PDLSCs was investigated by the MTT method (at 24 and 72 hours) and scratch test (at 0, 24, and 48 hours), respectively. Finally, the antioxidant effect of LCFSs was assessed by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay and ferric reducing/antioxidant power methods.

 The antibacterial properties of different concentrations of acidic and neutral LCFSs derived from three studied probiotic bacteria on S. mutans and A. actinomycetemcomitans were observed within the range of 12.5 - 50% (v/v) (1/8 - 1/2 dilutions with culture medium). Although there were no significant toxic (~ 100% viability) and wound healing effects on PDLSCs when the cells were exposed to either acidic or neutral studied LCFSs in a concentration of 5% (v/v), they showed significant antioxidant activity (~ 90% DPPH inhibition and 0.5 mM Fe2+/L).

 The results revealed that 5% (v/v) 48-hour acidic and neutral supernatants of three studied probiotics might play a beneficial role in controlling periodontitis.

Since December 2019, the world has been grappling with an ongoing global COVID-19 pandemic. Various virus variants have emerged over the past two years, each posing a greater threat than its predecessors. The recent appearance of the omicron variant (B.1.1.529) has raised significant alarm within the field of epidemiology due to its highly contagious nature and rapid transmission rate. The omicron variant possessed mutations in the key receptor-binding domain (RBD) region, the S region, and these modifications have shown a notable impact on the strain's susceptibility to neutralizing antibodies. Developing safe and efficient vaccines to prevent a future severe acute respiratory outbreak of coronavirus syndrome 2 (SARS-CoV-2) is significant. Viral surface spike proteins are ideal targets for vaccines. This study aimed to find a multi-subunit chimeric vaccine. After conducting bioinformatics analysis, the recombinant spike (RS) protein of SARS-CoV-2 was deliberately designed and subsequently produced using E. coli expression systems. The immunogenicity of RS and neutralizing antibody responses were evaluated on immunized BALB/c mice. There was a significant difference in antibody titers between RS-immunized mice and control groups. The endpoint of the serum antibody titer of mice immunized with our chimeric protein was 2.5 times higher than that of the negative control. The chimeric construct could present multiple antigens simultaneously, influentially affecting immunization. Sera from mice vaccinated by RS could recognize the SARS-CoV-2 virus and neutralize antibodies. Our chimeric peptide could bind to antibodies in the serum of patients infected with different serotypes of the SARS-CoV-2 virus, such as alpha, delta, and omicron variants. The results indicated that the RS protein would be a potential novel antigenic candidate for subunit vaccine development and could be used as a useful alternative to generate diagnostic serological tests for SARS-CoV-2 infection.

 Abnormal DNA methylation patterns have been reported in various diseases, including different cancers. CRISPR/Cas9 is a low-cost and highly effective gene editing tool that has lately revolutionized biotechnology. Studies have shown that the CRISPR/Cas9 system can effectively target and correct methylation.

 Telomerase plays a survival role for cancer cells. It is encoded by the hTERT gene. The effectiveness of CRISPR/Cas9 in targeting hTERT to treat glioma cancer cells was assessed in this study.

 EF1a-hsaCas9-U6-gRNA vector carrying sgRNA and Cas9 hybrids were used to transfect U87 glioma cells. Four and eight μg/mL polybrene concentrations were investigated to improve transfection efficiency. The expression level of hTERT that has undergone metabisulfite modification was assessed using real-time PCR. Flow cytometry and Western blotting were also used to determine whether telomerase was present in the cells. High-resolution melting analysis (HRM) was used to examine the hTERT promoter's methylation. Finally, flow cytometry was used to measure the apoptotic rate of transfected U87 cells.

 The findings demonstrated that gRNA significantly boosted transfection effectiveness. Significant variations were seen in the expression of hTERT in U87 cells at 4 μg/mL polybrene and 80 μg/mL transfection compared to transfection without gRNA and basal cells. Flow cytometry showed a decrease in hTERT levels in transfected cells. Furthermore, transfection with gRNA increased U87 cell apoptosis compared to transfection without gRNA.

 It appears that the designed CRISPR/Cas9 system can reduce hTERT expression and telomerase activity and thus inhibit glioma cell growth.

 Fibroblast growth factor 21 (FGF21) is a metabolic, endocrine hormone regulating insulin sensitivity, energy expenditure, and lipid metabolism. It has significant potential as a therapeutic drug for treating type 2 diabetes and obesity. However, the clinical efficacy of FGF21 analogs is limited due to their instability and short half-life. Glucagon-like peptide 1 (GLP-1) receptor agonists have been recognized as effective medications for type 2 diabetes mellitus and obesity over the past two decades.

 This study designed a new long-acting dual-agonist, exendin-4/FGF21, utilizing albumin-binding-designed ankyrin repeat proteins (DARPins) as carriers. The purified fusion proteins were subcutaneously injected into mice for pharmacokinetic and biological activity studies.

 Ex-DARP-FGF21 had a high binding affinity for human serum albumin (HSA) in vitro and a prolonged half-life of 27.6 hours in vivo. Bioactivity results reveal that Ex-DARP-FGF21 significantly reduced blood glucose levels in healthy mice. Moreover, compared to Ex-DARP alone, the Ex-DARP-FGF21 dual agonist displayed enhanced blood glucose lowering bioactivity and superior body weight management in the diet-induced obesity (DIO) mouse model.

 These results indicate that the long-acting dual agonist of exendin-4 and FGF21 holds considerable potential as a treatment for type 2 diabetes mellitus (T2DM) and obesity in the future.

 It remains unclear which formulation of the corticosteroid regimen has the optimum efficacies on COVID-19 pneumonia.

 The aim of this study was to compare the clinical outcomes of 2 different regimens in the treatment of acute respiratory distress syndrome (ARDS) caused by COVID-19: Methylprednisolone at a dose of 1 mg/kg every 12 hours (low-dose group) and 1000 mg/day pulse therapy for 3 days following 1 mg/kg methylprednisolone every 12 hours (high-dose group).

 In this randomized clinical trial, patients with mild to moderate ARDS due to COVID-19 were randomly assigned to receive either low-dose (n = 47) or high-dose (n = 48) intravenous methylprednisolone regimens. Two groups were matched for age, gender, body mass index (BMI), comorbidities, leukocytes, lymphocytes, neutrophil/lymphocyte, platelet, hemoglobin, and inflammatory markers (erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], and ferritin). Both regimens were initiated upon admission and continued for 10 days. The clinical outcome and secondary complications were evaluated.

 Evaluating in-hospital outcomes, no difference was revealed in the duration of intensive care unit (ICU) stays (5.4 ± 4.6 vs. 4.5 ± 4.9; P = 0.35), total hospital stays (8 ± 3.1 vs. 6.9 ± 3.4; P = 0.1), requirement rate for invasive ventilation (29.2% vs. 36.2%; P = 0.4) or non-invasive ventilation (16.6% vs 23.4%; P = 0.4), and hemoperfusion (16.6% vs 11.3%; P = 0.3) between the low- and high-dose groups. There was no significant difference in fatality due to ARDS (29.2% vs. 38.3%; P = 0.3) and septic shock (4.2% vs. 6.4%; P = 0.3) between the low- and high-dose groups. Patients in the high-dose group had significantly higher bacterial pneumonia co-infection events compared with those in the low-dose group (18.7% vs 10.6%; P = 0.01).

 The use of adjuvant pulse therapy with intravenous methylprednisolone did not result in improved in-hospital clinical outcomes among patients with mild to moderate ARDS due to COVID-19. A higher risk of bacterial pneumonia should be considered in such cases as receiving a higher dose of steroids.

 Drug-induced parkinsonism (DIP) is one of the most common movement disorders in approximately 20 - 35% of patients on antipsychotic medications. Managing the symptoms of DIP is challenging due to the limited number of potentially effective medications. On the other hand, this restricted possible treatment could have numerous side effects that ultimately result in patients stopping the medication all at once. The neuroprotective property of Ginkgo biloba extract (EGb) emerged as an effective commodity for the additional treatment of psychiatric disorders.

 This study aimed to evaluate the efficacy of EGb in psychiatric patients with symptoms of DIP.

 A sample of 63 patients who met the inclusion criteria were recruited and randomly assigned to control and experimental groups. Both groups were followed for 3 months. One group received 80 mg of G. biloba three times a day, and the control group received a placebo. The patients were evaluated using the Unified Parkinson’s Disease Rating Scale and Montreal Cognitive Assessment.

 Ginkgo could change the intensity of rest tremors, the severity of motor symptoms, rigidity, and bradykinesia. Ginkgo biloba might alleviate the severity of parkinsonism and motor symptoms and could lead to changes in the two components of working memory and short-term memory.

 Ginkgo biloba extract can be used as an effective and safe treatment in the management of DIP, whether in patients diagnosed with psychotic disorders or mood disorders.

 Gestodene (GEST) is widely used in female contraception. It is currently being used as an oral contraceptive. However, unfortunately, oral contraceptives are often associated with several bothersome side effects and poor compliance. Therefore, a sustained delivery system for GEST to overcome these shortcomings is highly desirable.

 The present study successfully developed a kind of novel dissolving microneedles (DMNs) with a potential for sustained release and a minimally invasive intradermal treatment of GEST.

 The dissolving microneedles containing GEST were fabricated using polyvinylpyrrolidone as the base material. The characteristics in vitro and pharmacokinetics in vivo of GEST-loaded DMNs were investigated.

 The results showed that the microneedle could pierce the porcine skin and release the drug at an average dose of 20µg/cm2 daily for seven days. The pharmacokinetic experiment of the microneedles indicated that the plasma level of GEST in rats increased with increasing drug dosage, and the plasma drug concentration-time curves were much flatter compared with subcutaneous injection and oral administration. In addition, no cutaneous irritation was observed.

 GEST-loaded DMNs may be a promising intradermal sustained delivery system for contraceptive use.

 The solubility of drugs in water and organic solvents is a crucial factor in numerous pharmaceutical processes. In recent years, a new type of solvent called deep eutectic solvents (DESs) has been developed as a useful solvent for drugs. Choline chloride-glycerol/urea (ChCl-G/U) systems are DESs recognized as a novel category of environmentally friendly solvents. One recent application of this type of DES in water is the solubilization of drugs.

 This study aimed to investigate the solubility of certain drugs in ChCl-G/U. In addition, the solubilization mechanisms of the DESs studied, and quantitative structure-property relationship (QSPR) models for solubilization were proposed.

 The solubility of 13 drugs in an aqueous solution of the ChCl-G/U system was investigated using the shake flask method. The study was conducted at 10% and 50% mass fractions of the studied systems. Multiple linear regression models were used to develop mathematical relationships between the solubilization of the studied compounds in the presence of ChCl-G/U + water mixture using QSPR models.

 The solubility of the compounds showed a significant increase upon adding ChCl-G/U to the aqueous solutions. Based on the data obtained, QSPR models were developed using solubilization ratio and structural descriptors.

 The experimental data demonstrates the potential of utilizing ChCl-G/U as a medium to enhance the solubility of poorly soluble drugs in water. Solubilization of solutes in ChCl-G/U + water mixtures could be correlated with the structural properties of drugs. Moreover, the final pH of the solutions in ChCl-U is a critical factor that must be considered when using this system for solubilization.

 The available drugs for the treatment of leishmaniasis are highly toxic and extremely expensive, with low efficiency; therefore, the development of effective therapeutic compounds is essential.

 The present study aimed to explore the antileishmanial effects of ethyl acetate extract, methanol extract, and fractions 1-4 (F1-F4) of Ferula tabasensis, alone or in combination with shark cartilage extract (ShCE), on L. major in vitro.

 In this study, ethyl acetate, methanol, and n-hexane extracts were extracted from the aerial roots of F. tabasensis by the maceration method. The silica gel column chromatography was used to separate n-hexane extracts at varying polarities (F1-F4 fractions). Subsequently, the effects of extracts and fractions against promastigotes were assessed by the parasite counting method microscopic inhibition test and MTT assay. Besides, their effects on the infected macrophage cells and the number of amastigotes were investigated. Cytotoxicity was evaluated in non-infected J774A.1 macrophage cells. Finally, apoptosis induction of promastigotes, including infected and non-infected macrophages, was evaluated.

 The results indicated the highly potent activity of F. tabasensis extracts and F1-F4 fractions, alone or in combination with ShCE, against L. major promastigotes and amastigotes in a dose-dependent manner (P < 0.05). The F1 fraction and methanol extract showed markedly higher toxicity compared to the other extracts and fractions, with 50% inhibitory concentrations (IC50/72h) of 2.4 ± 0.29 and 2.9 ± 0.55 µg/mL against promastigotes and 1.79 ± 0.27 µg/mL and 1.39 ± 0.27 µg/mL against amastigotes (P < 0.001). Moreover, they had a high selectivity index (SI) due to the low toxicity of macrophages (P < 0.0001). The results of flow cytometry indicated that the percentages of apoptotic promastigote cells in contact with IC50 concentrations of F1 and methanol extract alone after 72 h were 43.83 and 43.93%, as well as 78.4%, and 65.45% for their combination with ShCE, respectively.
Also, apoptosis of infected macrophages induced by F1 and methanol extracts was estimated at 68.5% and 83.7%, respectively.

 In this study, the F1 fraction and methanol extract of F. tabasensis showed potent efficacy against L. major, associated with low toxicity and apoptosis induction. Therefore, they can be promising therapeutic candidates in future animal and even human studies.

 Spirulina is a cyanobacteria species containing various bioactive compounds. Spirulina is a known source of nutrients in some traditional diets. Different activities have been reported for various extracts of S. platensis.

 In this study, the polysaccharide content of culture media and biomass extract of one species of Spirulina was partially purified, and its analgesic and anti-inflammatory effects were evaluated.

 Spirulina platensis PCST5 was cultured in a sterile Zarouk medium at 27°C and 16/8h of light/ dark exposure cycle for 25 days. Then, the polysaccharide content of biomass and cell-free culture medium samples (BPSs and CFPSs, respectively) was partially purified. The analgesic and anti-inflammatory effects were evaluated using animal models.

 16S rRNA gene analysis confirmed that the organism was genetically similar to Spirulina platensis. The CFPSs (30 and 100 mg/kg) and BPSs (30 mg/kg) significantly reduced pain-related behaviors in rats. Similarly, all samples could significantly reduce carrageenan-induced paw inflammation volume compared with the control group. Our results suggest Spirulina's polysaccharide fractions (CFPSs and BPSs) had significant analgesic and anti-inflammatory effects.

 Since Spirulina is a readily available source of bioactive compounds, finding such potent anti-inflammatory and anti-nociceptive compounds can provide promising leads for novel drug development.

 Antimicrobial compounds are used in animal husbandry to prevent and treat bacterial diseases and as illegal growth-promoting agents. Due to the excessive and inappropriate use of antibiotics, the antibiotic residues in milk can cause allergic reactions and antibiotic resistance. A rapid biochip-based method for the multi-analyte screening of 6 families of antibiotic residues (quinolones, ceftiofur, florfenicol, streptomycin, tylosin, and tetracyclines) in milk was validated based on Commission Decision 2002/657 and the European guidance for screening methods for veterinary medicinal products.

 This methodology allows the 6 antibiotic families to be detected simultaneously, increasing the screening capacity and reducing costs in test settings. The method's applicability was shown by screening 38 UHT cow milk samples taken from Tehran province, IR Iran.

 The results showed that the positive threshold T was above Fm, and the CCβ was below the European Commission's Maximum Residue Limit (MRL) (100 ppb for ceftiofur and tetracycline and 50 ppb for tylosin in milk). Norfloxacin was detected in about 8% of the samples and tylosin in 2.63%. The total antibiotic concentration in UHT cow milk samples was lower than the European Commission's MRL.

 This study showed that the biochip technique is valid for screening tylosin, ceftiofur, streptomycin, tetracycline, norfloxacin, and florfenicol in milk. It was found that the method was easy, quick, and capable of detecting 6 families of antibiotic residues simultaneously from a single milk sample without sample preparation.

 This study aims to investigate the effects of Bacillus coagulans T4 and Lactobacillus paracasei TD3 probiotics on skeletal muscle inflammation and oxidative stress in C57BL/6J mice fed a high-fat diet (HFD).

 Probiotics B. coagulans T4, and L. paracasei TD3 were administered to male C57BL/6J mice fed with HFD. The gene expression of macrophage infiltration markers, inflammatory cytokines, and oxidative stress indicators in the muscle tissue was investigated.

 Treatment with B. coagulans T4 and L. paracasei TD3 reduced macrophage infiltration, accompanied by a decrease in the expression of monocyte chemoattractant protein-1 (MCP-1) and an increase in the expression of interleukin (IL)-10. On the other hand, L. paracasei TD3 decreased malondialdehyde (MDA) while B. coagulans T4 decreased carbonyl and increased catalase activity.

 Treatment with probiotics B. coagulans T4 and L. paracasei TD3 partially ameliorated obesity-induced skeletal muscle inflammation in HFD-fed mice.

In the present work, the chemical composition of extract fractions of the Atropa belladonna plant growing in the north of Iran was investigated by HPTLC, HPLC, and GC-MS. Based on HPLC results, atropine, and scopolamine were found to be higher in the fruit and leaf extracts than in other parts of the plant. The comparative GC-MS analysis showed that diacetone alcohol, mesityl oxide, palmitic acid, and linoleic acid were the major bioactive components in the root, stem, leaf, and fruit extracts, respectively. Leaf extract showed the best antioxidant activity in the DPPH test. The antibacterial activity of fractional extracts was determined against Pseudomonas aeruginosa using the MIC method, and the fruit and leaf extracts exhibited the best antibacterial activities. The leaf extract was embedded into nanofibers by electrospinning technique, and its antibacterial activity was determined against Pseudomonas aeruginosa. The morphology and mechanical properties of the nanofibers were studied with SEM, contact angle, and tensile analysis, showing ultrafine fibers with uniform morphology.

 Bone marrow-derived mesenchymal stem cell (BMSC) transplantation has become an effective method for treating neurodegenerative diseases.

 This study investigated the effect of 3-N-butylphthalide (NBP) on the neuronal differentiation of BMSCs and its potential mechanism.

 In this study, a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was performed to detect cell proliferation and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining was conducted to detect the apoptosis of BMSCs. Quantitative real-time polymerase chain reaction (RT-qPCR) and Western blot analysis were performed to detect the messenger RNA (mRNA) and protein expression levels, respectively. An enzyme-linked immunosorbent serologic assay assessed the levels of interleukin-1β, tumor necrosis factor-α, and cyclic adenosine monophosphate (cAMP). Moreover, a flow cytometry assay was used to detect the proportion of active β-tubulin III (TUJ-1) cells, and TUJ-1 expression was observed by immunofluorescence assay.

 The results showed that a low concentration of NBP promoted the proliferation and induction of BMSC neuronal differentiation while inhibiting apoptosis, the production of inflammatory factors, and p65 expression. Compared with differentiation induction alone, combined NBP treatment increased the levels of nestin, neuron-specific enolase (NSE), TUJ-1, and microtubule-associated protein 2 (MAP2) protein, as well as the ratio of TUJ-1-positive cells and cAMP expression. Furthermore, p65 overexpression weakened the effect of NBP, and the overexpression of hairy and enhancer of split homolog-1 (HES1) reversed the effect of NBP in the induction of BMSC neuronal differentiation in vitro.

 We confirmed that NBP exhibited potential therapeutic properties in the stem cell transplantation treatment of neurodegenerative diseases by protecting cells and promoting BMSC neuronal differentiation by inhibiting the p65/HES 1 pathway.

 Hemorrhage control and anti-infection play a crucial role in promoting wound healing in trauma-related injuries.

 This study aimed to prepare nanoparticles with dual functions of hemostasis and antibacterial properties.

 The dual-functional nanoparticles (CDCA-PLL NPs) were developed using a self-assembly method based on the electrostatic forces between Poly-L-lysine (PLL) and Chenodeoxycholic acid (CDCA). The physicochemical properties, hemostatic properties, and antibacterial activities were investigated.

 The prepared nanoparticles displayed a spherical structure, exhibiting a high drug loading capacity, encapsulation efficiency, and good stability. The CDCA-PLL NPs could reduce the hemolysis caused by PLL and promote the proliferation of human fibroblasts, indicating excellent biosafety. Moreover, CDCA-PLL NPs demonstrated a shorter in vivo hemostasis time and reduced blood loss in mouse tail vein hemorrhage, femoral vein hemorrhage, femoral artery hemorrhage, and liver hemorrhage models. Also, CDCA-PLL NPs showed excellent antibacterial efficacy against E. coli and S. aureus.

 CDCA-PLL NPs have great potential to be extensively applied as a hemostatic and antibacterial agent in various clinical conditions.

 Tissue engineering is the application system that tries to restore damaged tissues by different approaches, such as cellular therapy, application of cell differential factors, and various materials. One of the important goals in tissue engineering is to guide stem cells directly to the desired tissue, and researchers tried to utilize different molecules as effective factors to improve this technique.

 This study aims to demonstrate the effects of diacerein, a slow-acting drug for the treatment of osteoarthritis, on mesenchymal stem cell proliferation and evaluate its potential in the chondrogenesis process.

 Stem cells were isolated from adipose tissue, characterized by flow cytometry, and cells were treated with 10-5M diacerein for three weeks. Chondrogenic gene expression of SOX9, COL2A1, ACAN, and TGFB1 were analyzed by qRT-PCR and immunocytochemistry techniques.

 Our results showed that diacerein increased the expression of the following genes involved in chondrogenesis: SOX9 (2.9-fold, P < 0.00), COL2A1 (2.2-fold, P < 0.00), ACAN (2.7-fold, P < 0.00), and TGFB1 (2.6-fold, P < 0.00). Immunocytochemistry results also showed increased production of collagen type II as the main protein marker for chondrocytes.

 We observed that diacerein alone could initiate and enhance chondrogenesis, and it can be used as a differentiation factor for stem cells to chondrocyte besides its ability to inhibit IL-1β. Knowing the actual function of diacerein, it could be a good candidate for the treatment of osteoarthritis.

 The rise of antibiotic resistance has become a major concern, signaling the end of the golden age of antibiotics. Bacterial biofilms, which exhibit high resistance to antibiotics, significantly contribute to the emergence of antibiotic resistance. Therefore, there is an urgent need to discover new therapeutic agents with specific characteristics to effectively combat biofilm-related infections. Studies have shown the promising potential of peptides as antimicrobial agents.

 This study aimed to establish a cost-effective and streamlined computational method for predicting the antibiofilm effects of peptides. This method can assist in addressing the intricate challenge of designing peptides with strong antibiofilm properties, a task that can be both challenging and costly.

 A positive library, consisting of peptide sequences with antibiofilm activity exceeding 50%, was assembled, along with a negative library containing quorum-sensing peptides. For each peptide sequence, feature vectors were calculated, while considering the primary structure, the order of amino acids, their physicochemical properties, and their distributions. Multiple supervised learning algorithms were used to classify peptides with significant antibiofilm effects for subsequent experimental evaluations.

 The computational approach exhibited high accuracy in predicting the antibiofilm effects of peptides, with accuracy, precision, Matthew's correlation coefficient (MCC), and F1 score of 99%, 99%, 0.97, and 0.99, respectively. The performance level of this computational approach was comparable to that of previous methods. This study introduced a novel approach by combining the feature space with high antibiofilm activity.

 In this study, a reliable and cost-effective method was developed for predicting the antibiofilm effects of peptides using a computational approach. This approach allows for the identification of peptide sequences with substantial antibiofilm activities for further experimental investigations. Accessible source codes and raw data of this study can be found online (hiABF), providing easy access and enabling future updates.

Hemangiomas are benign vascular tumors that often develop in infants. The most common treatment option for complicated hemangiomas is propranolol. We discuss the use of oral propranolol in treating infantile hemangioma (IH) in an Iranian population at our hospital. We conducted a cross-sectional prospective descriptive study on 62 infants aged 1 to 16 months from 2017 to 2021. Propranolol was gradually administered orally at a dose of 3 mg/kg/day. The hemangioma score was examined at 6 intervals (first visit, 1, 3, 6, 9, and 12 months later). Propranolol therapies were stopped when there was no further decrease in scores for 2 successive visits. The study was completed by 62 patients. In terms of hemangiomas, 46 (74.2%) patients had 1 lesion, 12 (19.4%) had 2 lesions, and 4 (6.5%) had 3 lesions. Over time, the average size of hemangiomas steadily decreased, such that 5 patients (9.1%) were completely treated; 1 patient improved after 3 months, 3 after 6 months, 1 after 9 months, and 57 (91.9%) were partially treated. Aside from being safe and effective, propanol can also obtain a higher response rate when treatment is started early in infants aged less than 3 months.

 Parkinson’s disease (PD) is one of the common neurodegenerative diseases, and there has been an increasing interest in the potential role of intestinal dysbiosis in its pathogenesis and related gastrointestinal complications such as constipation.

 This study aims to evaluate the effects of multi-strain probiotics on constipation and motor function in PD patients.

 This study was a blinded, randomized controlled trial (RCT) that involved 27 PD patients who were diagnosed with constipation according to the ROME IV criteria for functional constipation. The primary outcome measured before and after the intervention in both the placebo and probiotic groups was the frequency of defecation. Secondary outcomes evaluated were laxative use, sense of complete evacuation, Bristol Stool Scale for consistency, and Unified Parkinson’s Disease Rating Scale (UPDRS) scale. The study lasted for eight weeks. Both groups also were educated about lifestyle modification.

 Of 30 included patients (15 in each group), 13 were women, and 17 were men. Three patients dropped out of the study. Between-group analysis showed that the frequency of bowel movements significantly increased in the probiotic group 4 [3 - 5] in comparison with 2 [2 - 3] in placebo (P = 0.02). Stool consistency also improved in the probiotic group (P = 0.04). However, there were no significant differences in other outcomes. The within-group analysis showed improvement in stool consistency in both probiotics and placebo groups (P = 0.01 and P = 0.007, respectively), while stool frequency and sense of complete evacuation significantly improved only in the probiotic group (P < 0.05).

 This study demonstrated that multi-strain probiotics could improve frequency, consistency, and sense of complete evacuation in PD patients, while there was no significant effect on motor functions in 8 weeks. It is suggested that additional studies be conducted on longer-term effects.

 The emergence and rapid global spread of the coronavirus disease 2019 (COVID-19) has presented a significant global health challenge. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infects human host cells through the interaction of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2), which serve as main regulators for viral entry. Specifically, ACE2 and TMPRSS2 genes are influenced by two microRNAs: miR-200b-3p and miR-214-3p, respectively. The objective of this study was to explore the association between the serum levels of miR-200b-3p and miR-214-3p and the presence of circulating ACE2 and TMPRSS2 in severe and non-severe cases of COVID-19.

 This study sought to examine the potential utility of microRNAs as biomarkers for assessing disease severity and progression. Additionally, the study aimed to elucidate the interplay between microRNAs and the ACE2 and TMPRSS2 proteins, which play crucial roles in facilitating SARS-CoV-2 viral entry and infection.

 This practical-foundational study involved the collection of samples from 61 hospitalized patients with confirmed COVID-19 and 31 healthy individuals. Subsequently, the enzyme-linked immunosorbent assay (ELISA) technique was utilized to measure the concentrations of ACE2 and TMPRSS2 in the blood samples. Additionally, the expression levels of serum miR-200b-3p and miR-214-3p were analyzed using real-time polymerase chain reaction (PCR). The statistical analysis of the data was conducted using GraphPad Prism software (version 8.02) and SPSS software (version 19.0), ensuring the accurate interpretation of results.

 The findings revealed significant increases in the peripheral blood concentrations of ACE2 and TMPRSS2 in patients with non-severe COVID-19, compared to healthy individuals (P < 0.001 and P < 0.01, respectively). Similarly, patients with severe COVID-19 exhibited higher serum levels of ACE2 and TMPRSS2 than healthy subjects (P < 0.0001). Additionally, the serum levels of miR-200b-3p and miR-214-3p were decreased in both non-severe and severe COVID-19 patients, compared to healthy individuals (P < 0.01 and P < 0.0001, respectively). Moreover, a decrease in the serum levels of both miR-200b-3p and miR-214-3p was observed in patients with severe COVID-19, compared to those with non-severe cases (P < 0.001). Furthermore, this study identified a negative correlation between miR-200b-3p and ACE2 serum levels and between miR-214-3p and TMPRSS2 peripheral blood levels.

 The above-mentioned findings suggest that miR-200b-3p and miR-214-3p might be potential biomarkers for disease severity and prognosis in COVID-19 patients.

 Froriepia subpinnata is one of the plants used in the diet of Iranian people. Previous studies have investigated the antioxidant and antibacterial effects of this plant extract, but no study has been conducted on its anticancer properties.

 In this study, we investigated the effect of F. subpinnata extract on MCF-7 breast cancer cells.

 The inhibitory effect of F. subpinnata leaf extract was determined on the growth of cancer cells by the MTT test. The ROS (reactive oxygen species) test was used to investigate the impact of the extract on intracellular oxidative stress. Flow cytometry and real-time PCR tests were used to investigate the apoptosis-related molecular processes. The GC-MS analysis was performed to determine the most abundant components.

 The GC-MS analysis showed that phytol, mono-ethylhexyl phthalate (MEHP), cinnamaldehyde, and neophytadiene constituted 60% of the extracted content. The MTT assay demonstrated that F. subpinnata leaf extract caused 50% lethality at a 400 μg/mL dose in MCF7 cells. The F. subpinnata extract at low doses decreased the ROS level for 24 hours in MCF-7, but by increasing the concentration, the ROS levels increased. At the IC50 dose (inhibitory concentration (IC) associated with 50% impact), the ROS level increased 3.5 times compared to the control group. Examining the effect of N-acetyl cysteine (NAC) showed that this antioxidant agent could prevent the lethal impact of the extract and eliminate the ROS increase in MCF7 cells. Flow cytometry and real-time PCR results showed that the extract specifically induced apoptosis through the internal apoptosis pathway in this cancer cell line.

 The F. subpinnata extract induced apoptosis by increasing ROS in MCF-7 cancer cells and can be considered for further studies.

Since several Helicobacter pylori strains have become resistant to metronidazole, new nitroimidazole derivatives based on metronidazole were designed and synthesized with different substituents on imidazole nitrogen. The activity of the synthesized compounds was evaluated against 20 clinically isolated metronidazole-resistant H. pylori strains. Some synthesized compounds were effective against those metronidazole-resistant H. pylori strains. Three compounds exhibited the most potent inhibitory activities (MIC50 = 8 µg/mL and MIC90 = 16 µg/mL).

 The development of platinum-based metal complexes in oncology is limited due to vigorous toxicity and drug resistance.

 This work aimed to study the cytotoxic activity and apoptosis induction of ruthenium complexes in a B16F10 cell line therapy.

 We prepared a series of innovative Ru(II) complexes [Ru(Tzphen)(bpy)(dcbpy)]+2 (S1), [Ru(dcbpy)2(Tzphen)]+2 (S2), [Ru(Phen)2(Tzphen)]+2 (S3), [Ru(Tzphen)(bpy)2]+2 (S4), [Ru(dmbpy)2(Tzphen)]+2 (S5) based on 1,10-phenanthroline ligand containing tetrazole and their anticancer properties investigated by cytotoxicity in vitro, reactive oxygen species, apoptosis with annexin V/PI staining method, autophagy, and cell uptake.

 S1, S2, S3, S4, and S5 complexes showed comparable cytotoxicity activity relative to cisplatin against the B16F10 model. Moreover, intracellular ROS levels increased due to the presence of the complexes. Among the investigated complexes, the cells treated with the S5 complex indicated the highest apoptotic percentage (Q3) of 14.9% compared to the controls. The cell adsorption of the complexes also showed that the S4 and S5 complexes had higher cell adsorption, better internalization, and higher fluorescence light intensity.

 The present work provides important guidance for designing and using Ru complexes in cancer therapy.

 Two mangostin compounds, gamma-mangostin and alpha-mangostin, show anticancer properties through the inhibition of cell proliferation and cell migration. Metastatic triple-negative breast cancer (TNBC) cells, including MDA-MB-231, highly express C-X-C chemokine receptor type 4 (CXCR4) to maintain reactive oxygen species (ROS) and cell migration.

 This study was performed to analyze and compare different modes of action of γ-mangostin and α-mangostin as antimigratory effects targeted on CXCR4 in MDA-MB-231 as a model of TNBC cell.

 This study investigated the effect of γ-mangostin and α-mangostin using a series of assays, including Cell Counting Kit-8 (CCK-8) assay for cytotoxicity, wound healing assay for migration study, quantitative real-time polymerase chain reaction (qRT-PCR) for gene expression analysis, and flow cytometry for ROS measurement, along with in silico study to observe the binding between the compound and CXCR4.

 The findings revealed half maximal inhibitory concentration (IC50) values of 25 and 20 μM for γ-mangostin and α-mangostin in MDA-MB 231 cells, respectively. Moreover, a concentration of 10 μM was used for the migration assay. Both γ-mangostin and α-mangostin significantly suppressed cell migration within 24 hours. The present gene expression studies revealed the downregulation of key migration-associated genes, namely Farp, CXCR4, and LPHN2, upon γ-mangostin treatment but not α-mangostin. Additionally, both γ-mangostin and α-mangostin increased cellular ROS generation, highlighting the same effect of γ-mangostin and α-mangostin ROS elevation to inhibit cancer cell migration. Molecular docking simulations further suggested a potential interaction between γ-mangostin and α-mangostin with CXCR4 in high affinity.

 These findings suggest that both γ-mangostin and α-mangostin inhibit breast cancer cell migration and induce cellular ROS levels in MDA-MB-231 cells; notably, γ-mangostin suppresses CXCR4 mRNA expression that might correlate to its activity to inhibit MDA-MB-231 cell migration.

In recent years, metal-organic frameworks (MOFs) have gained attention in the biomedical field, particularly as drug carriers for treating tumors. Therefore, we decided to synthesize a novel benzoic acid Zn-based MOF and study the Zn-based MOFs' drug-delivery properties and the drug-delivery system's anticancer effects. This study successfully synthesized a zinc-based MOF using solvent thermal synthesis. The crystal structure of a Zn-based MOF was investigated using thermogravimetric analysis, X-ray diffraction, and Fourier transform infrared spectroscopy. Subsequently, the results of UV spectrophotometry showed that Doxorubicin was successfully loaded with a loading amount of 33.74%. Furthermore, the drug release experiments demonstrated that the Zn-based MOF was pH-sensitive, releasing more at a pH of 3.8 than at pH 5.8 or 7.4. Finally, the Zn-based MOF loaded with drugs exhibited high antitumor activity against HepG2 cells while demonstrating remarkably low toxicity to normal cells (LO2). Taken together, these results demonstrate that the Zn-based MOF has the potential to serve as a carrier in the field of drug delivery systems.

 Overactive bladder (OAB) is a symptomatic condition characterized by urinary urgency with or without incontinence, usually associated with frequent daytime urination, enuresis, and nocturia.

 This economic evaluation was aimed at assessing the cost-effectiveness of mirabegron versus solifenacin in the treatment of OAB patients from a payer’s perspective in Iran.

 A Markov model with a 5-year time horizon was used. The model consisted of five health states, and OAB patients with an average age of 60 years entered the cycle from the persistent state. Transition probabilities were based on published trials, clinical judgments, and expert opinions. Resource use and costs, including those for medications and adverse events, were extracted from the literature and tariff book, and all costs are presented in 2019 US dollars with a 5% discount rate for the costs and utilities. The incremental cost-effectiveness ratio (ICER) and quality-adjusted life-years (QALYs) were computed for medications, and sensitivity analyses were used to test the robustness of the results.

 Average per-patient treatment costs were 24,720.724,668.6 for mirabegron and solifenacin, respectively. Mirabegron was expected to produce higher QALYs than solifenacin (3.20 vs. 3.19). Mirabegron had an ICER of 531.3802709/QALY.

 Compared to solifenacin, mirabegron was more cost-effective in OAB patients in the Iranian healthcare system.

 A significant number of pregnancies are at risk of threatened abortion (TA). Different types of progesterone are used to treat TA.

 In this study, the effects of 2 forms of progesterone on the continuation of pregnancy and TA-caused pregnancy outcomes were compared.

 A total of 190 women with a gestational age of 6 - 13 weeks presenting with uterine bleeding, closed cervix, and absence of fetal heart rate diagnosed by vaginal examination and ultrasound were allocated into 2 groups and treated with either (D) dydrogesterone (10 mg twice a day) or (M) micronized progesterone (200 mg, twice a day) for beyond 2 weeks after the cessation of uterine bleeding to ensure that bleeding would not recur. The participants were followed up and received prenatal care until the end of pregnancy. The outcomes of pregnancy were recorded and compared between the 2 groups.

 The incidence of preeclampsia, gestational diabetes, cesarean section, intrauterine fetal death (IUFD), placenta previa, and abortion was not significantly different between the 2 groups. However, the prevalence of preterm labor and low birth weight (LBW) was significantly lower in M-treated women (P < 0.001 and P = 0.007, respectively). The baby’s weight and gestational age at delivery were significantly higher in the M group than in the D group (P < 0.001). No serious drug side effects were observed in the 2 groups throughout the study.

 The results of this study showed that the incidence of preterm labor and LBW was significantly lower in the patients treated with micronized progesterone than in patients treated with dydrogesterone; however, the prevalence of preeclampsia, gestational diabetes, cesarean section, IUFD, and abortion was not significantly different between the 2 groups.

 A significant number of pregnancies are at risk of threatened abortion (TA). Different types of progesterone are used to treat TA.

 In this study, the effects of 2 forms of progesterone on the continuation of pregnancy and TA-caused pregnancy outcomes were compared.

 A total of 190 women with a gestational age of 6 - 13 weeks presenting with uterine bleeding, closed cervix, and absence of fetal heart rate diagnosed by vaginal examination and ultrasound were allocated into 2 groups and treated with either (D) dydrogesterone (10 mg twice a day) or (M) micronized progesterone (200 mg, twice a day) for beyond 2 weeks after the cessation of uterine bleeding to ensure that bleeding would not recur. The participants were followed up and received prenatal care until the end of pregnancy. The outcomes of pregnancy were recorded and compared between the 2 groups.

 The incidence of preeclampsia, gestational diabetes, cesarean section, intrauterine fetal death (IUFD), placenta previa, and abortion was not significantly different between the 2 groups. However, the prevalence of preterm labor and low birth weight (LBW) was significantly lower in M-treated women (P < 0.001 and P = 0.007, respectively). The baby’s weight and gestational age at delivery were significantly higher in the M group than in the D group (P < 0.001). No serious drug side effects were observed in the 2 groups throughout the study.

 The results of this study showed that the incidence of preterm labor and LBW was significantly lower in the patients treated with micronized progesterone than in patients treated with dydrogesterone; however, the prevalence of preeclampsia, gestational diabetes, cesarean section, IUFD, and abortion was not significantly different between the 2 groups.

 Polycystic ovary syndrome (PCOS) affects women of reproductive age globally with an incidence rate of 5% - 26%. Growing evidence reports important roles for microRNAs (miRNAs) in the pathophysiology of granulosa cells (GCs) in PCOS.

 The objectives of this study were to identify the top differentially expressed miRNAs (DE-miRNAs) and their corresponding targets in hub gene-miRNA networks, as well as identify novel DE-miRNAs by analyzing three distinct microarray datasets. Additionally, functional enrichment analysis was performed using bioinformatics approaches. Finally, interactions between the 5 top-ranked hub genes and drugs were investigated.

 Using bioinformatics approaches, three GC profiles from the gene expression omnibus (GEO), namely gene expression omnibus series (GSE)-34526, GSE114419, and GSE137684, were analyzed. Targets of the top DE-miRNAs were predicted using the multiMiR R package, and only miRNAs with validated results were retrieved. Genes that were common between the “DE-miRNA prediction results” and the “existing tissue DE-mRNAs” were designated as differentially expressed genes (DEGs). Gene ontology (GO) and pathway enrichment analyses were implemented for DEGs. In order to identify hub genes and hub DE-miRNAs, the protein-protein interaction (PPI) network and miRNA-mRNA interaction network were constructed using Cytoscape software. The drug-gene interaction database (DGIdb) database was utilized to identify interactions between the top-ranked hub genes and drugs.

 Out of the top 20 DE-miRNAs that were retrieved from the GSE114419 and GSE34526 microarray datasets, only 13 of them had “validated results” through the multiMiR prediction method. Among the 13 DE-miRNAs investigated, only 5, namely hsa-miR-8085, hsa-miR-548w, hsa-miR-612, hsa-miR-1470, and hsa-miR-644a, demonstrated interactions with the 10 hub genes in the hub gene-miRNA networks in our study. Except for hsa-miR-612, the other 4 DE-miRNAs, including hsa-miR-8085, hsa-miR-548w, hsa-miR-1470, and hsa-miR-644a, are novel and had not been reported in PCOS pathogenesis before. Also, GO and pathway enrichment analyses identified “pathogenic E. coli infection” in the Kyoto encyclopedia of genes and genomes (KEGG) and “regulation of Rac1 activity” in FunRich as the top pathways. The drug-hub gene interaction network identified ACTB, JUN, PTEN, KRAS, and MAPK1 as potential targets to treat PCOS with therapeutic drugs.

 The findings from this study might assist researchers in uncovering new biomarkers and potential therapeutic drug targets in PCOS treatment.

 The emergence of multidrug resistance among nosocomial pathogens has prompted researchers to look for new antibacterial sources. Metal nanoparticles and probiotic products have attracted the attention of researchers. However, combination therapy is an attractive alternative in this field.

 This study evaluated the antibacterial activity and toxicity of Zinc Oxide nanoparticles (ZnO-NPs) combined with Cell-free Supernatant (CFS) of Lactobacillus plantarum (L. plantarum) and Lactobacillus acidophilus (L. acidophilus) alone and in a novel mixture.

 Antibacterial effects and cytotoxic properties of ZnO-NPs, CFS of L. plantarum (SLP), and CFS of L. acidophilus (SLA) were determined alone and in a mixture against ESKAPE strains. In addition, the viability percentage of the cells was evaluated after exposure to these agents.

 Antibacterial mixtures (ZnO-NPs with SLP or ZnO-NPs with SLA) demonstrated synergistic and additive effects against Pseudomonas aeruginosa (FIC≤0.75), Acinetobacter baumannii (FIC = 1), and Escherichia coli (FIC≤0.75). The viability percentage of the cells after 24 h of exposure to a mixture of ZnO-NPs and SLA (about 50%) was more than when the cells were exposed to ZnO-NPs alone (about 30%) at the same concentration.

 A mixture of ZnO-NPs and CFS of probiotics can be an alternative to antibiotics, with more effectiveness and fewer side effects.

 Wheat grains are susceptible to mycotoxins, toxic natural secondary metabolites generated by certain fungi on agricultural produce in the field during growth, harvest, transportation, or storage. Therefore, wheat flour can be contaminated with mycotoxins, which seriously threaten human health.

 A rapid method for screening seven mycotoxins in wheat flour was validated in accordance with Commission Decision 2002/657/EC. With this multi-analytical screening method, 7 prevalent mycotoxins (fumonisin B1, ochratoxin A, aflatoxin G1, deoxynivalenol, T-2 toxin, aflatoxin B1, and zearalenone) can be determined simultaneously. The method’s applicability was demonstrated by screening 7 mycotoxins in 39 wheat flour samples collected from different bakeries in Tehran province, Iran.

 The validation results indicated that for all 7 mycotoxins, the positivity threshold (T) was above the cut-off value (Fm), and no false positive results were obtained for any of the mycotoxins. The screening results of 12 packaged and 27 bulk wheat flour samples indicated that the concentrations of all mentioned mycotoxins were higher than the cut-off (in the relative light unit [RLU]), and all the samples were compliant.

 The present study revealed that the biochip-based technique is valid for identifying and assessing the levels of 7 mycotoxins in grain samples, such as wheat flour, at the measured validation concentrations. The method was simple, fast, and able to screen 7 mycotoxins simultaneously. The test process of the kit is easy to conduct, and the results are straightforward to interpret.

 Cerasomes, due to their external siloxane network, demonstrate markedly higher physicochemical stability and, therefore, easier handling and storage than liposomes.

 The main objective of this study was to compare the pharmacokinetics (PK) of cerasome and liposome following intravenous administration. The PK of PEGylated and non-PEGylated cerasomes was also compared to see whether the presence of a hydrophilic siloxane network on the surface of cerasomes can play the role of polyethylene glycol (PEG) in increasing the blood circulation of these vesicles.

 Silver sulfide (Ag2S) quantum dots (Qds)-loaded PEGylated and non-PEGylated cerasomes and PEGylated liposomes were fabricated and thoroughly characterized in terms of particle size, polydispersity index, zeta potential, entrapment efficiency, and in vitro stability. For pharmacokinetic evaluation, the free Qds and the selected formulations were intravenously injected into rats, and blood samples were collected for up to 72 hours. Pharmacokinetic parameters were calculated by the non-compartmental method.

 Both cerasomal and liposomal carriers significantly improved the PK of Qds. For example, the elimination half-life (t1/2) and the area under the plasma concentration-time curve from time 0 to time infinity (AUC0-∞) for the free Qds were 4.39 h and 8.01 µg/mL*h and for cerasomal and liposomal formulations were 28.82 versus 26.95 h and 73.25 versus 62.02 µg/mL*h, respectively. However, compared to each other, the plasma concentration-time profiles of PEGylated cerasomes and liposomes displayed similar patterns, and the statistical comparison of their pharmacokinetic parameters did not show any significant difference between the two types of carriers. For PEGylated cerasomes, t1/2 and AUC0-∞ values were respectively 1.6 and 3.3 times greater than the classic cerasome, indicating that despite the presence of a hydrophilic siloxane network, the incorporation of PEG is necessary to reduce the clearance of cerasomes.

 The comparable PK of PEGylated cerasomes and liposomes, along with the higher physicochemical stability of cerasomes, can be considered an important advantage for the clinical application of cerasomes. Additionally, the easy surface functionalizing ability of cerasomes confers a dual advantage over liposomes. The study findings also showed that the presence of a hydrophilic siloxane network on the surface of cerasomes alone is not enough to make them circulate long.

 Neuroinflammation and oxidative stress are critical factors involved in the pathogenesis of Parkinson's disease (PD), the second most common progressive neurodegenerative disease. Additionally, lipid peroxidation end products contribute to inflammatory responses by activating pro-inflammatory genes. Lipid peroxidation occurs as a result of either the overproduction of intracellular reactive oxygen species (ROS) or the reaction of cyclooxygenases (COXs).

 In this study, we examined the role of 1,5-diaryl pyrrole derivatives against the neurotoxic effects of 6-hydroxydopamine (6-OHDA) in a cellular model of PD.

 PC12 cells were pre-treated with compounds 2-(4-chlorophenyl)-5-methyl-1-(4-(trifluoromethoxy)phenyl)-1H-pyrrole (A), 2-(4-chlorophenyl)-1-(4-methoxyphenyl)-5-methyl-1H-pyrrole (B), and 1-(2-chlorophenyl)-2-(4-chlorophenyl)-5-methyl-1H-pyrrole (C), respectively, 24 h before exposure to 6-OHDA. We conducted various assays, including 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazoliumbromide (MTT), ROS, and lipid peroxidation assays, Hoechst staining, Annexin V/PI, Western blotting analysis, and prostaglandin E2 (PGE2) determination, to assess the neuroprotective effects of pyrrole derivatives on 6-OHDA-induced neurotoxicity.

 Our results demonstrated that apoptosis induction was inhibited by controlling the lipid peroxidation process in the in vitro model following treatment with compounds A, B, and, somehow, C. Furthermore, compounds A and C likely act by suppressing the COX-2/PGE2 pathway, a mechanism not attributed to compound B.

 These findings suggest that the novel synthetic pyrrolic derivatives may be considered promising neuroprotective agents that could potentially prevent the progression of PD.

 Epsilon toxin (ETX), produced by Clostridium perfringens, is one of the most ‎potent toxins ‎known, with a lethal potency approaching that of botulinum neurotoxins. Epsilon toxin ‎is responsible ‎for enteritis. Therefore, the development of rapid and simple methods to ‎detect ETX ‎is imperative. Aptamers are single-stranded oligonucleotides that can bind ‎tightly to specific ‎target molecules with an affinity comparable to that of monoclonal antibodies (mAbs). ‎DNA aptamers ‎can serve as tools for the molecular identification of organisms, such as ‎pathogen subspecies.‎

 This study aimed to isolate high-affinity single-stranded DNA (ssDNA) ‎aptamers against ETX.‎

 This study identified aptamers using the Systematic Evolution of Ligands by Exponential Enrichment (SELEX) method, enzyme-linked apta-sorbent assay (ELASA), and surface plasmon resonance (SPR) to determine ‎the affinity and ‎specificity of the newly obtained aptamers targeting ETX. ‎

 Several aptamers obtained through the ‎SELEX process were studied. Among them, 2 aptamers, ETX clone 3 (ETX3; dissociation constant (Kd = 8.4 ± 2.4E-9M) ‎and ETX11 (Kd = 6.3 ± 1.3E-9M) had favorable specificity for ETX. The limits of detection ‎were 0.21 and 0.08 μg/mL for ETX3 and ETX11, respectively.‎

 The discovered aptamers can be used in various aptamer-based rapid diagnostic tests for the detection of ETX.

 Metabolism reprogramming is a survival mechanism in acute myeloid leukemia (AML) cells in the tumor microenvironment. Therefore, we investigated the effect of signaling pathway inhibitors on the expression of genes rewired in the metabolic pathway of AML cells.

 HL-60 cells were treated with Idelalisib, MK-2206, and Everolimus, which respectively are selective inhibitors of phosphatidylinositol-3-kinase (PI3K), AKT, and the mammalian target of rapamycin (mTOR), either individually or in combination. The relative expressions of glucose transporter 1, hexokinase 2, pyruvate kinase, pyruvate dehydrogenase E1, citrate synthase, isocitrate dehydrogenase 2, and hypoxia inducible factor 1 subunit alpha were determined by real-time PCR.

 The combined treatment of HL-60 cells with Idelalisib, MK-2206, and Everolimus decreased the expression of glucose transporter 1, hexokinase 2, pyruvate kinase M2, pyruvate dehydrogenase E1, citrate synthase, isocitrate dehydrogenase 2, and hypoxia inducible factor 1 subunit alpha.

 A combination of PI3K/AKT/mTOR pathway inhibitors regulates the expression of genes involved in glycolysis, pyruvate dehydrogenase complex (PDH), and the tricarboxylic acid (TCA) cycle and interferes with metabolic reprogramming and immune evasion mechanisms of AML leukemic cells. Combinational therapy approaches to block these pathways might be a promising and novel therapeutic strategy for targeting the metabolic requirements of AML cells.

 Decision-making is a complex process, and most studies showed that patients with mild cognitive impairment (MCI) make worse decisions than healthy people.

 This study aims to evaluate the effect of rivastigmine on the decision-making of MCI patients using the Cambridge Neuropsychological Test Automated Battery (CANTAB) tests.

 The study was conducted at the Roozbeh Hospital neurology clinic, and 30 patients with mild cognitive impairment over 40 years old were randomly recruited to receive rivastigmine or placebo twice daily for 12 weeks. The initial dose of rivastigmine or placebo was 1.5 mg twice daily and was increased to 3 mg twice daily per patient compliance. A CANTAB test was conducted before and following the intervention.

 The mean age of patients in the rivastigmine group was 58.93 ± 10.88, and in the placebo group was 59.33 ± 10.34. The median MMSE (Mini-Mental State Examination) was 26 (IQR = 25 - 26) in both groups. Patients in the rivastigmine group showed significant differences in all subgroup tests of CGT, IST, and SST except in risk adjustment in the CGT test, discrimination in the IST test, and median correct RT on the go trial and SSRT in the SST test. The most commonly reported adverse effects were gastrointestinal complications.

 According to the results, rivastigmine significantly improved the primary decision-making outcomes in comparison with placebo.

 There is a general theme in studying employees in the research and development (R&D) department individual performance studies, where tremendous attention has been paid to innovation performance compared to behavioral and particularly extra-role behavior of employees in this department.

 This study investigates the relationship between sustainable human resource management (s-HRM) and organizational citizenship behavior (OCB) through the mediating role of organizational identification (OI) in R&D employees.

 A standard questionnaire was used to evaluate s-HRM, OI, and OCB. Five hundred questionnaires were delivered to all employees of the research and development departments of 59 Iranian pharmaceutical companies, and finally, 316 completed questionnaires were collected.

 The results of data analysis with WarpPls software revealed a positive and significant relationship between s-HRM and OI, as well as OI and OCB. Investigating the mediating role of OI showed that OI partially mediates the relationship between s-HRM and OCB. The model was checked in terms of its fit indices, which were evaluated as favorable.

 The findings suggest that s-HRM improves employees' willingness to go beyond their defined job description to display in OCB. Additionally, they imply that strengthening OI can improve OCB in employees.

 Infections caused by pathogenic microorganisms have increased the need for hospital care and have thus represented a public health problem and a significant financial burden. Classical treatments consisting of traditional antibiotics face several challenges today. Anti-microbial peptides (AMPs) are a conserved characteristic of the innate immune response among different animal species to defend against pathogenic microorganisms.

 In this study, a new peptide sequence (mCHTL131-140) was designed using the in silico approach.

 Cathelicidin-2 (UniprotID: Q2IAL7) was used as a potential antimicrobial protein, and a novel 10 - 12 amino acids sequence AMP was designed using bioinformatics tools and the AMP databases. Then, the anti-bacterial, anti-biofilm, and anti-fungal properties of the peptide, as well as its hemolytic activity and cytotoxicity towards human fibroblast (HDF) cells, were investigated in vitro.

 Online bioinformatics tools indicated that the peptide sequence could have anti-bacterial, anti-viral, anti-fungal, and anti-biofilm properties with little hemolytic properties. The experimental tests confirmed that mCHTL131-140 exhibited the best anti-bacterial properties against Acinetobacter baumannii and had fair anti-fungal properties. Besides, it did not cause red blood cell lysis and showed no cytotoxicity towards HDF cells.

 In general, the designed peptide can be considered a promising AMP to control hospital-acquired infections by A. baumannii.

Epilepsy, as a neurological disease, can be defined as frequent seizure attacks. Further, it affects many other aspects of patients’ mental activities, such as learning and memory. Scorpion venoms have gained notice as compounds with potential antiepileptic properties. Among them, Buthotus schach (BS) is one of the Iranian scorpions studied by Aboutorabi et al., who fractionated, characterized, and tested this compound using electrophysiological techniques in brain slices (patch-clamp recording). In the present study, the fraction obtained from gel electrophoresis was investigated through behavioral and electrophysiological assays. At first, ventricular cannulation was performed in rats, and then the active fraction (i.e., F3), carbamazepine, and the vehicle were microinjected into the brain before seizure induction by the subcutaneous (SC) injection of pentylenetetrazol (PTZ). Seizure behaviors were scaled according to Racine stages. Memory and learning were evaluated using the Y-maze and passive avoidance tests. Other groups entered evoked field potential recording after microinjection and seizure induction. Population spike (PS) and field excitatory postsynaptic potential (fEPSP) were measured. The F3 fraction could prevent the fifth stage and postpone the third stage of seizure compared to the control (carbamazepine) group. There was no significant improvement in memory and learning in the group treated with the F3 fraction. Also, PS amplitude increased significantly, and long-term potentiation was successfully formed after the high-frequency stimulation of the performant pathway. Our results support the antiepileptic effects of the F3 fraction of BS venom, evidenced by behavioral and electrophysiological studies. However, the effects of this fraction on memory and learning were not in the same direction, suggesting the involvement of two different pathways.

In addition to clinical and technical considerations, patients’ preferences are essential for evaluating interventions such as precision medicine (PM).

This study aimed to identify and prioritize attributes of precision oncology that are important for patients to develop and validate a standard stated preference instrument.

The key attributes of precision oncology and their related levels were extracted from the systematic literature review and were presented on a validated 5-point Likert scale questionnaire to experts (n = 35). In two rounds of Delphi, participants scored and prioritized the attributes through this personally administered questionnaire to identify the five most important ones to develop a discrete choice experiment (DCE) instrument. The developed DCE questionnaire was subsequently validated, providing a robust and standard instrument for evaluating patients’ preferences for precision oncology.

Based on the consensus criteria, the final DCE included four attributes and a total of 14 levels, which were access to treatment (easy/not easy), out-of-pocket (OOP) expenditures (four levels according to treatment costs in the country), change in life expectancy (LE, six levels from an average gain of three months to four years), and change in quality of life (QoL, improvement or no change).

The above-mentioned attributes represent patients’ main preferences from the views of the Iranian experts. The developed DCE questionnaire can be used to assess patients’ preferences and willingness to pay (WTP) in precision oncology.

A novel series of thiadiazole compounds was synthesized through the reaction of thiosemicarbazone intermediates with 2, 3-dichloro-5, 6-dicyano-1, 4-benzoquinone (DDQ). The antiplatelet activity of the synthesized compounds was evaluated using an aggregation test with adenosine diphosphate (ADP) and arachidonic acid (AA) as platelet aggregation inducers. Among the synthesized analogs, compound 3b exhibited the most potent inhibition of platelet aggregation induced by ADP (half maximal inhibitory concentration [IC50] = 39 ± 11 μM). Molecular docking studies of 3b revealed hydrogen bonds between the nitrogen of the thiadiazole ring and Lys280. The tolyl ring exhibited hydrophobic interactions with Tyr105, similar to the antagonist co-crystallized with P2Y12 (PDB ID: 4NTJ). These compounds have the potential to serve as lead molecules for designing P2Y12 inhibitors.