Pharmaceutical Sciences
Volume:27 Issue: 4, Dec 2021

Polo-like kinase 1(Plk1) plays an essential role in inhibiting cell proliferation and comes under the family of serine/threonine-protein kinase, which is a particular target for cancer therapy. In some clinical studies, Plk1 has been identified as a target for cancer. Currently, so many scientists are developing the Plk1 inhibitors, and they are thinking about working on them. A recent strategy for Plk1 inhibition is the development of small-molecule inhibitors, which will inhibit the Plk1 through the ATP-binding site of the Plk1. Now new generation Plk1 inhibitors being tested clinically, which are targeting the polo box domain. This review highlights the recent progress made in the development of Plk1 inhibitors as anticancer agents

Oral and dental diseases are among the common health conditions which can have different effects on the individuals’ health and quality of life. The objective of this study was to examine the effect of garlic ( Allium sativum) extract on saliva Streptococcus mutans (primary outcome) and its side effects (secondary outcome).

In the present systematic review and meta-analysis, English and Persian databases (PubMed, Cochrane Library, Google Scholar, Scopus, SID, and Magiran) were systematically searched until February 25, 2021. The quality of the included studies was examined using Co - chrane handbook, and the meta-analysis was carried out using RevMan 5.3. Heterogeneity of the studies was analyzed by index I2. Moreover, the quality of the evidence was assessed through GRADE approach.

A total of 93 studies were found on the databases; 89 articles were screened by title and abstract review and were removed as 19 studies were repetitive and 70 studies were unrelated to the subject under study. Ultimately, 4 articles with a sample size of 171 participants were included in this study, and two of the four studies were meta-analyzed. In all four studies, garlic extract was effective in reducing the number of saliva Streptococcus mutans colonies compared to the control group. The results of the meta-analysis showed that using garlic extract mouth - wash significantly decreased the average number of saliva Streptococcus mutans colonies (Mean Difference: -3.32; 95%CI: -4.39 to -2.26; P<0.00001).

Although this review study indicated the significant effect of garlic extract in reducing saliva Streptococcus mutans, the evidence is not sufficient enough to recommend garlic extract to fight saliva Streptococcus mutans, and more clinical trials with stronger designs and larger sample sizes are needed.

Many of the known coronaviruses cause a wide range of respiratory infections in humans, and the novel coronavirus is no exception to this rule. Although no drug has yet been discovered to prevent or treat this disease, chloroquine (CQ) and hydroxychloroquine (HCQ) have been widely used in studies showing different results.

The present study is an umbrella study. The search was conducted for the articles published from January 2020 to November 2020 using the keywords (“COVID-19” OR “SARS- CoV-2” AND “Hydroxychloroquine“ OR “Chloroquine” AND “Systematic Review” OR “Metanalysis”). This study was limited to human samples and systematic reviews with or without meta-analysis. The quality of the articles was also evaluated independently by two researchers.

To evaluate the clinical efficacy of HCQ and CQ, a total of 176 papers and 643569 cases ranging from patients with mild pneumonia to intubated critically ill patients were evaluated. Finally, 8 studies were included.

There are conflicting results regarding HCQ or CQ efficacy and safety in the systematic reviews. More evidence is needed to confirm whether these drugs are useful in COVID-19 infection, and their usage as the standard care cannot be recommended based on the majority of the studies included in this umbrella review.

It is undeniable that many patients worldwide suffer from various types of wounds, especially chronic wounds. The complex and intricate process of wound healing has a severe impact on the patient’s quality of life as well as causing an economic burden on healthcare institutions. Although various new therapies have become available for treating patients with acute and chronic wounds for the past decade, the available therapies are often expensive or accompanied by undesirable side effects. Hence, the discovery of a new arsenal for wound healing remains a hot topic of research. Recently, plants or herbs and their derivatives have garnered significant attention as a source of therapeutic agents to treat wounds. This is because plants provide a rich reservoir of phytochemicals that could potentially become effective and affordable therapeutic agents. Thus, the present review attempted to outline wound healing mechanisms and analysed some renowned medicinal plants with potential wound healing properties from the existing literature from various electronic databases. This review also sheds light on the plant’s underlying molecular mechanisms and, wherever available, acknowledges the biologically active substances found in these plants.

Single-stranded nucleic acids can fold and create unique 3-dimensional structures when interacting with other molecules. The unique structure can achieve high specificity and affinity for the particular target. Synthetic oligonucleotide binding agents, also known as aptamers, are generated through the rational process of Systematic Evolution of Ligands by Exponential Enrichment (SELEX). As this technology matures, it shows increasing promise for use in the field of therapeutic drugs, drug discovery, development, and delivery, and this report seeks to detail how this technology may be applied.

Learning and memory may decline due to Alzheimer’s disease (AD) in older adults. A reduction in cyclic guanosine monophosphate concentration and an increase in phosphodiesterase activity have been reported in the process of aging. Although phosphodiesterase (PDE) type 5 inhibitor, Tadalafil is used to treat erectile dysfunction; PDE inhibitors possibly prevent cognition impairment in aging. This study was designed to investigate the effects of tadalafil on memory in middle-aged and young healthy and AD rats.

Memory impairment was induced by intracerebroventricular (ICV) administration of streptozotocin (STZ; 3 mg/kg) in AD rats. Male Wistar rats (middle-aged and young) were distributed into six groups as follows: two control, two AD, and two AD+tadalafil (1 mg/kg) groups. Saline or tadalafil was administered once a day orally for 40 consecutive days. Animals were tested using novel object recognition (NOR), passive avoidance learning (PAL), and Morris water maze (MWM) tests.

Aged AD rats exhibited a significant impairment in cognition in the NOR test and impaired learning and memory in PAL and MWM tests compared with the control aged rats. Tadalafil treatment in aged AD rats significantly improved the discrimination index in the NOR test, decreased the time spent in the dark compartment in the PAL test, and increased time spent in the target quadrant in MWM tests compared with aged AD rats. In young AD rats, treatment with tadalafil significantly enhanced cognition, learning, and memory in the NOR, PAL, and MWM tests compared with young AD rats treated with saline.

Tadalafil treatment in aged rats improves cognition and memory after STZ-induced (ICV) memory impairment.It can be concluded that chronic treatment with tadalafil is protective against cognitive, learning, and memory impairment in both young and aged subjects.

Spermatogenesis is a programmed route for germ cell proliferation and differentiation that can produce abundant numbers of spermatozoa. The antioxidants play a vital role in decreasing oxidative stress production in cells; therefore, the extraction of plants with antioxidant property can prevent cell damage. In the present study, antioxidant effects of Calligonum extract on proliferation and colonization rate of spermatogonial cells were assessed.

After isolation and culturing of spermatogonial stem cells (SSCs) on neonatal mice (4-5 days old) and identification by PLZF and Oct4 markers, the therapeutic effect ofCalligonum comosum extract on cells treated with H2O2 was measured. The cultured cells were divided into four groups: Control, Calligonum, H2O2 and Calligonum + H2O2 groups. Induced oxidative stress cells were treated with 10 μg/ml extract for 3 weeks. Reactive oxygen species (ROS) levels were assessed by the flow cytometry, and proliferation and total antioxidant capacity (TAC) were evaluated by cell count and ferric reducing ability of plasma (FRAP) assay, respectively. Also, the apoptosis rate was measured with P53 and Bax genes by the real- time PCR method.

After three-week treatment, ROS level was significantly lower in the Calligonum group than in the H2O2 group. Antioxidants levels were significantly higher in Calligonum group than in the H2O2 group (P≤0.05). There was also a strong inverse relationship between the two groups. Proliferation and colonization rate were significantly higher in Calligonum + H2O2 group than in H2O2 group (P≤0.05). Finally, the results suggested that P53 and Bax expression decreased in Calligonum + H2O2 group compared to H2O2 group.

The results of present study revealed that 30 μM doses of H2O2 increased oxidative stress and apoptosis on the one hand and decreased proliferation of SSCs on the other hand. As a plant with antioxidant effect, Calligonum could reduce the level of ROS and apoptosis, and increase proliferation, colonization rate and TAC.

Green Curmin is a soluble curcumin extract product made in Thailand that has been reported to reduce gastric inflammation. Inflammatory cytokines including IL-1α, IL-6, and TNF-β play a crucial role in cancer cell migration, which is a major development towards poor prognosis. The aim of this study is to investigate the effects of Green Curmin on colon cancer cell growth and migration, which involve pro-inflammatory cytokines.

Curcuma longa L. were extracted and named Green Curmin. The cytotoxicity of the Green Curmin-treated HCT116-colon cancer cells was obtained by 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry. The effect of the extract on cancer migration was investigated with a wound-healing assay. In addition, fibroblast- associated cancer migration was confirmed by using the Transwell migration assay. Pro- inflammatory cytokines were also determined.

Green Curmin had cytotoxicity in the induced-cancer cell apoptosis at concentrations of 1 and 5 mg/ml. However, reduced colon cancer migration and fibroblast associated-cancer migration was found at concentrations of 0.05 and 0.1 mg/ml (non-toxicity dose), respectively. They also suppressed pro-inflammatory cytokines expression including IL-1α, IL-6, and TNF-β in colon cancer cells and IL-6 in fibroblast cells.

Green Curmin has the potential to suppress pro-inflammatory cytokines and reduce fibroblast associated-cancer migration.

Co-administration of two or several either chemotherapeutic agents or conventional drugs as a combination treatment is the most effective method to increase therapeutic efficiency. Additive or synergistic influence are two mechanisms by which combination therapy causes a rise in optimal cancer therapy compared to a single treatment.

Colorimetric assay was carried out to estimate the cytotoxicity of the combined system, followed by apoptosis assay to calculate the number of apoptotic cells. Both 4 ′,6-diamidino- 2-phenylindole (DAPI) staining and DNA ladder were complemented tests to illuminate morphological changes and DNA fracturing on HeLa cancer cells.

We revealed that the combination of berberine ( BER) and methotrexate (MTX) could inhibit the growth of HeLa cancer cells noticeably. Nevertheless, single BER and MTX were not as effective as a combined system to reduce cell viability at the same dose. Regarding the apoptosis induction and change in morphology of cancer cells’ nucleus, co-treatment of BER and MTX was more effective. The result was complemented with flow cytometry, DAPI staining and DNA ladder, which showed that BER+MTX depicted more anti-cancer effects.

The combination therapy of HeLa cancer cells with BER and MTX showed high inhibition effect compared to other treated groups.

Pinus roxburghii has been used in the Himalayan region as folkloric remedy while nothing is yet known about its immunomodulatory potential.

The crude extracts of green and fallen pine needles were subjected to sequential fractionation to get partially purified fractions. Human peripheral blood lymphocytes (PBL) were used to analyze immunoenhancing potential of these fractions. Microcytotoxicity assay was employed to investigate improved cancer cells killing capabilities of PBL against various cancer cell lines. GC-MS was carried out to identify the major compounds in the bioactive fractions.

The lymphocyte proliferation assay depicted the immunoenhancing potential of extracts and fractions of fallen and green needles of P. roxburghii . The ethyl acetate fractions of both fallen and green needles displayed highest mitogenic activity on human PBL. Both fractions heightened the expression of cell surface markers (CD3, CD8, and CD56) and significantly increased the production of cytokines (IL-2, IFN-γ and TNF-α). The enhanced intracellular granulysin (immunomarker for activated CTLs and NK cells) expression also confirmed immune stimulatory potential of these fractions on human lymphocytes. The ethyl acetate fractions of pine needles enhanced the cytotoxicity of PBL towards various cancer cells (HCT-116, HeLa, PC-3 and A549) as compared to untreated PBL. GC-MS analysis showed presence of major compounds like 3-α-mannobiose, octakis (trimethylsilyl) ether, methyloxime in ethyl acetate fraction of the green needles and cyclodecasiloxane, eicosamethyl in ethyl acetate fraction of the fallen needles.

The bioactive fractions of the fallen and green needles of P. roxburghii stimulate cancer cells killing potential of human lymphocytes.

Acute lymphoblastic leukemia (ALL) is a fetal hematologic disorder that is mostly observed in children. Both B and T lymphocytes have been reported to play a role in ALL etiology. Long non-coding RNAs (lncRNAs) are large regulatory molecules with more than 200 nucleotides that participate in various cellular processes. Methylation at the promoter regions of these regulatory molecules has been reported to vary between ALL patients and healthy controls. This study aimed to evaluate methylation status at promoter regions of lncRNAs between these two groups.

In the current study, 80 ALL patients and 80 healthy controls were enrolled. The intravenous blood samples were obtained from all patients and controls. The extracted DNA from blood samples underwent sodium bisulfite treatment. Thereafter, methylation levels in the promoter regions of lncRNAs RP11-137H2.4, RP11-624c23.1, RP11-203E8, RP11-446E9, and RP11-68118.10 were evaluated using methylation specific-high resolution melting (MS-HRM). Moreover, the receiver operating characteristic curve (ROC) analysis was performed to examine the sensitivity and specificity of the tests.

The methylation levels of all studied lncRNAs including RP11-137H2.4, RP11-624c23.1, RP11-203E8, RP11-446E9, and RP11-68118.10 were significantly increased (p<0.05). ROC curve analysis also showed that all lncRNAs could be used as diagnostic markers.

This study showed that methylation alterations of lncRNAs could be considered as novel biomarkers for early detection of ALL. Furthermore, owing to the possible role of studied lncRNAs as tumor suppressors, they could be reliable treatment targets for methylation modifications. Further research is still required to elucidate the role of these lncRNAs in ALL etiology.

Given the potential anti-ischemic effects of allopurinol, we aimed to assess whether allopurinol administration may reduce myocardial injury following non-ST elevation myocardial infarction (NSTEMI).

A randomized clinical trial (RCT) was conducted on 100 individuals with NSTEMI. The intervention group (n=50) received 600 mg oral allopurinol at the time of diagnosis of NSTEMI, followed by 300 mg every day for two next days and the standard treatment of NSTEMI, while the control group (n=50) received only the standard treatment. Serum concentrations of cardiac troponin I (cTnI) were measured at baseline, and 8, 16, 24, and 32 hours after the treatment.

The baseline demographic and clinical data of the patients were not statistically different between the intervention and control groups (all P > 0.05). The comparing estimated marginal mean ± standard error for cardiac troponin I (cTnI) levels revealed no significant difference between the study groups (2.93 ± 0.27, 2.25 ± 0.27; P=0.082). The linear mixed model results showed that the interaction of time and group was not statistically different (P=0.751). Moreover, there was a decreasing trend over time for cTnI in both groups (P=0.039).

The present pilot RCT did not support the potential cardio-protective benefits of allopurinol administration on decreasing myocardial injury following NSTEMI.

Statins are the most common drugs used for reducing low-density lipids (LDL). In addition to their lipid-lowering effects, they have well-documented anti-inflammatory actions. The goal of this study was to compare the effects of high dose atorvastatin and rosuvastatin on lipid profiles and high sensitivity C Reactive Protein (hs-CRP) in patients undergoing percutaneous coronary intervention (PCI).

The study was done between October 2017 and September 2018 in Semnan Kowsar Hospital. In this randomized trial, 69 patients with atherosclerotic coronary artery disease were randomly assigned 1:1 to receive atorvastatin (80 mg daily) or rosuvastatin (40 mg daily) for 4 months. Levels of hs-CRP and lipid profiles including cholesterol, triglyceride, low-density lipids (LDL), and high-density lipids (HDL) were measured and compared before and after the treatments. Lipid profiles were measured at baseline, 2 months, and 4 months of the treatment.

Sixty patients completed the study. The mean age was 61.1 ± 6.6 years with an excess of males. After 4 months, both drugs could significantly reduce LDL levels, however, the between- group differences were not statistically significant. Rosuvastatin significantly increased HDL levels (p < 0.05). In addition, triglyceride levels had a significant reduction in both groups, yet the differences were not significant. Both drugs caused significant reductions in hs-CRP levels (p < 0.05). Moreover, the effects of treatments were seen in drug naïve patients as well as patients who were on statins prior to the trial.

The results indicate that high dose therapies with atorvastatin and rosuvastatin have similar effects on lipid profiles and hs-CRP levels in patients undergoing PCI.

Chlorzoxazone (CHZ) is a water-insoluble drug having bioavailability problems. The absorption rate of such drugs can be improved by reducing their particle size. In this work, the crystal growth kinetics of CHZ–ethanol for different degrees of supersaturation (SS) has been studied.

The equilibrium solubility data of CHZ in ethanol is determined by the shake-flask method within the 283.15–313.15 K temperature range. The mole fraction solubility of CHZ is calculated and correlated with the modified Apelblat equation, λh equation, van’t Hoff equation, Wilson, and non-random two liquid (NRTL) equation. Batch crystallization experiments are performed on three different degrees of SS-1.16, 1.18, and 1.20 at 293.15 K as a function of time.

The maximum root mean square difference (RMSD) and relative average deviation (RAD) values of 169.24 x10 -6 and 0.699 x10-2, respectively, are observed in the NRTL equation model. The dissolution properties such as standard enthalpy, standard entropy, and Gibbs free energy are predicted using van’t Hoff equation. Using a simple integral technique, the average crystal growth rate constant KG is calculated as 1.58 (μm/min) (mg/ml) -1 and the order n=1 for CHZ–ethanol at 293.15 K.

The obtained result concludes that the crystal’s growth size is found to be varied at different SS ratio in batch crystallization. The particle size control in batch crystallization can be achieved by optimizing the operating conditions to get the desired size crystals.

Nitazoxanide (NTZ) is a broad spectrum antimicrobial agent with poor aqueous solubility and low bioavailability. Thus, the generation of new solid forms of NTZ is relevant to improve its unfavorable properties. The present study deals with the application of mechanochemistry for the preparation of alternate solid forms of NTZ, using saccharine (SAC) as coformer.

NTZ-SAC mixtures were prepared by neat and liquid-assisted grinding (LAG) and characterized using differential scanning calorimetry (DSC), hot stage microscopy (HSM), X-ray Powder Diffraction (XRPD), 13C Solid-state Nuclear Magnetic Resonance (SSNMR) and Diffuse Reflectance Infrared Fourier Transform (DRIFT) spectroscopy. Powder dissolution (PD) profiles were obtained with USP apparatus 2 in buffer phosphate pH 6.5 with 0.25% TweenÒ 80 - 0.25% triethanolamine and in 0.25% sodium lauryl sulfate, at 37 ºC ± 0.5 ºC and 75 rpm. Drug release was characterized in terms of dissolution efficiency (DE).

XRPD, SSNMR and DRIFT indicated that NTZ and SAC did not cocrystallize but DSC and HSM revealed that they formed a binary eutectic mixture which melted near 176 °C, a melting temperature lower than those of NTZ and SAC. PD data indicated that the 1:1 NTZ- SAC sample obtained by LAG exhibited a slightly higher DE than pure NTZ in the two assayed media.

NTZ and SAC formed a eutectic, the first reported for this drug, which improved its dissolution rate and opened the pathway for studies searching for new eutectics with better biopharmaceutical attributes than NTZ and the NTZ-SAC eutectic reported herein.