فهرست مطالب
Advanced Pharmaceutical Bulletin
Volume:12 Issue: 1, Jan 2022
- تاریخ انتشار: 1400/11/03
- تعداد عناوین: 22
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Pages 1-4Purpose
The new coronavirus, called SARS-CoV-2, is responsible for the recent global pandemic COVID-19. The status of the global pandemic COVID-19 is currently underway, and the virus has caused about 1.11 million deaths. Several SARS-CoV-2 vaccines are in phase 3 clinical trials. Pending the availability of safe and effective vaccines, pharmacological treatments are experimental and aimed at avoiding the most serious complications of the infection.
MethodsThis article explores and describes the scientific evidence in the literature and the scientific pharmacological and molecular rationale to consider drugs that modulate the renin- angiotensin system (RAS) system as therapeutic agents that if administered appropriately can help the host organism to fight SARS-CoV-2 infection.
ResultsIt is known from the 2003 SARS epidemic that the critical receptor for SARS-CoV entry into host cells is the angiotensin-converting enzyme 2 (ACE2), the strain involved in the current SARS-CoV-2 epidemic is similar to the SARS-CoV strain involved in the 2002-2003 SARS epidemic. ACE-2 is part of the RAS system, the modulation of this enzyme could be of therapeutic efficacy.
ConclusionDepending on pharmacological knowledge, and epidemiological evidence in the literature based on current knowledge of the mechanism of penetration of SARS-CoV-2 in cells, and the role of ACE-2 in the inflammatory state of infection, therapeutic treatments that modulate RAS could be a weapon to fight COVID-19 infection.
Keywords: ACE-2, RAS, COVID-19, Sars-CoV-2, Renin -
Pages 7-16
Medicinal plant is a major source of drug discovery for disease management. Over 85% of the population in Asia and in the Middle East use herbal medicine for disease management such as SARS caused by coronavirus. Infection from coronavirus is initiated by entry of the virus into a susceptible host cell. The two human coronaviruses of public health importance two decades ago were SARS-CoV and MERS-CoV and now SARS-CoV 2. These three viruses belong to the same class of beta coronavirus and are somewhat similar in genome sequencing, life cycle, mode of entry into a host, mode of transmission and clinical manifestations. This review identified twenty medicinal plants with potential inhibitory bioactive compounds from natural sources that are active against coronaviruses that could be developed into various drug delivery systems. It also highlighted several evidences to show that medicinal plant used in the treatment of SARS-CoV may offer some sort of relief from the burden of COVID 19 pandemic. Since there is no specific treatment for COVID 19 yet, the search for medicinal plants with inhibitory bioactive compounds against coronavirus could be the long awaited breakthrough scientists have been searching to change the narratives of Covid-19 pandemic.
Keywords: Medicinal plant, Bioactive compounds, Coronavirus, SARS-CoV -
Pages 17-33
Solid lipid nanoparticles are one of the developed technologies for addressing the bioavailability and targeting issues of drug delivery. In this review article, we attempted to incorporate all the essential details of SLNs like various methods of preparation, different models of SLNs, updated characterization methods, in-vivo behavior (Uptake), their applications, route of administration as well as advancements taken place in the field of delivery of biological drugs like gene vector, new adjuvant for vaccines, protein, and peptide with SLNs. Surface modified SLNs hold excellent potential for targeted and controlled drug delivery which is discussed and summarized. Based on the available data, the future success of SLNs is widened because they could be easily fabricated with various functionalities which would display enormous potential for targeting and diagnosing various diseases. This review would help the budding researchers to find out the unexplored areas of SLNs with the present discussion that reframes the potential of SLNs by gathering the various research findings of SLNs in tabular form along with the approved patent technologies of SLNs.
Keywords: Solid Lipid Nanoparticles (SLNs), Method of preparation, Route of administration, Biological drugs, Surface modified SLNs, Patents -
Pages 34-44
COVID-19 a global pandemic that has brought all the greater global countries to a hook. The novel coronavirus (SARS-CoV-2) outbreak was first reported in Wuhan, China which then started spreading to different countries around the world. Angiotensin-converting enzyme 2 (ACE2) receptors are present in various organs but the overexpression of ACE2 at lung epithelia makes them more vulnerable to respiratory symptoms. SARS-CoV-2 binds to ACE2 receptors for entry into host cells which may serve as potential target for future therapy .Repurposing of drugs are the present strategy undertaken as the SARS-CoV-2 shows similar respiratory distress symptoms as in the case of SARS and MERS. At present the antiviral medications and vaccines are at the early stages and may take few months to years, to achieve their complete efficacy to solve the public crisis. The technological advancements have brought passive immunisation, which is an anecdotal success, but the ideal approach to future outbreaks of SARS-CoV-2 is done by vaccines that are under clinical trials. There are a large percentage of population under psychological crisis either due to the fear of infection or stress from the quarantine lives. High levels of viral loads at the initial stages cause higher chances of transmission hence immediate isolations and screening methods must be undertaken. This review mainly focuses on the treatment strategies followed with no definitive approval from authorities. This is an attempt to gather all the materialistic evidences available for now.
Keywords: ACE2 receptors, Antiviral therapy, Coronavirus, COVID-19, Drug repurposing, SARS-CoV-2, Vaccines -
Pages 45-57
Transdermal delivery over the past decade has become the field of interest for drug delivery due to its various advantages such as no first-pass metabolism, increased drug bioavailability, and easy administration. Different vesicle systems like ethosomes, liposomes, niosomes, and transferosomes along with particle systems like lipid nanoparticles, polymeric nanoparticles, carbon nanotubes, and fullerenes have been developed. These vesicles and particle systems have been developed using various easy and effective methods like cold injection method, rotary film evaporation, thin film hydration, high shear homogenization, solvent extraction method, and many more. These drug delivery systems are a very effective and feasible option for transdermal drug delivery and further developments can be made to increase their use. This article explains in detail the preparation methods and applications for these drug delivery systems.
Keywords: Transdermal, Dermal, Vesicle systems, Particle systems, Niosomes, Ethosomes, Nanoparticles, Transferosomes, Drug delivery -
Pages 58-76
Antibiotic resistance is one of the serious health-threatening issues globally, the control of which is indispensable for rapid diagnosis and treatment because of the high prevalence and risks of pathogenicity. Traditional and molecular techniques are relatively expensive, complex, and non-portable, requiring facilities, trained personnel, and high-tech laboratories. Widespread and timely-detection is vital to the better crisis management of rapidly spreading infective diseases, especially in low-tech regions and resource-limited settings. Hence, the need for inexpensive, fast, simple, mobile, and accessible point-of-care (POC) diagnostics is highly demanding. Among different biosensing methods, the isothermal amplification of nucleic acids is favorite due to their simplicity, high sensitivity/specificity, rapidity, and portability, all because they require a constant temperature to work. Isothermal amplification methods are utilized for detecting various targets, including DNA, RNA, cells, proteins, small molecules, ions, and viruses. In this paper, we discuss various platforms, applications, and potentials of isothermal amplification techniques for biosensing of antimicrobial resistance. We also evaluate the potential of these methods, coupled with the novel and rapidly-evolving platforms offered by nanotechnology and microfluidic devices.
Keywords: Biosensing, Isothermal amplification techniques, Antibiotic drug resistance, Nanotechnology, Microfluidics -
Pages 77-85
Photochemical degradation of drugs can lead to degradation products with potential toxic or allergizing effects for the human body. A significant amount of work has been carried out over the past few decades to clarify the molecular mechanism of photosensitizing processes observed after the administration of certain drugs and exposure to light. There is a close relation between the photosensitizer effect of a drug and its chemical structure. Compounds possessing certain moieties and functional groups in their molecular structure, like aromatic chromophore systems or photo-dissociable bonds that can form free radicals, and consequently are susceptible to have light-induced adverse effects. Photoionization, photodissociation, photoaddition and photoisomerization are the main chemical processes, which can occur during the photochemical decomposition of a pharmaceutical compound. The current study is a short review describing photochemical degradation of certain pharmaceuticals, presenting specific examples from various pharmaceutical classes for the different types of decomposition mechanisms. In vivo methods and clinical tests available for the investigation of photosensitizing reactions are also discussed.
Keywords: Photochemical degradation, Photochemistry, Phototoxicity, Photoallergy, UV radiation -
Pages 86-92Purpose
To overcome the side effects of repetitive administration of diazepam (Dzp) besidesgaining benefits from sustaining release of the drug, which contributes to patient compliance,we concentrated on designing and preparing Dzp solid lipid nanoparticles (SLNs).
MethodsUsing cholesterol (CHOL), stearic acid (SA), and glycerol monostearate (GMS), SLNswere prepared by high shear homogenization technique coupled with sonication. Polysorbate80 (Tween 80) was used as a nonionic surfactant. After modification of prepared SLNs, particlesize, zeta potential, drug-loading efficiency, morphology, and scanning calorimetry, as well asrelease studies were conducted. To increase the stability of desired particles, freeze-drying bycryoprotectant was carried out. In the final stage, In vivo studies were performed by oral (PO)and intraperitoneal (IP) administrations to Wistar male rats.
ResultsResults indicated that optimized prepared particles were on average 150 nm diameterin spherical shape with 79.06 % loading efficiency and release of more than 85% of the loadeddrug in 24 hours. In vivo investigations also illustrated differences in blood distribution of Dzpafter loading this drug into SLNs.
ConclusionBased on the findings, it seems that drug delivery using SLNs could be anopportunity for solving complications of Dzp therapy in the future.
Keywords: Blood distribution, Diazepam (DZP), Drug delivery, Solid Lipid Nanoparticles (SLN), Sustained release -
Pages 93-101Purpose
The objective of this study was to design and develop nanoemulsion formulations of Itraconazole (ITZ), a water-insoluble, potent antifungal drug using the spontaneous emulsification method, to improve the ocular delivery and achieve a sustained release of the drug.
MethodsThe oil was selected on the basis of the ITZ solubility while the surfactant and co-surfactant were selected based on the thermodynamic stability and globule size. Following the selection of components, a pseudo-ternary phase diagram was constructed for the most promising formulation (F11) using benzyl benzoate (BB) as the oil, Eumulgin CO40 as the surfactant, and propylene glycol as the co-surfactant, by the design of experiments (DoE).
ResultsF7 and F11 formulations were found to have an average globule size of 223.5 ± 10.7 nm and 157.5 ± 14.2 nm, besides thermodynamic stability and suitable physicochemical properties. F11 possessed an almost seven-fold higher cumulative percentage of in vitro released ITZ, in comparison to ITZ aqueous suspension after 24 hours. The release data suggested that the best fitted kinetical model for F11 and F7 was the Higuchi and Korsmeyer-Peppas model.
ConclusionThe extended-release of the drug beside an acceptable amount of loaded ITZ suggested that nanoemulsion is suitable for the delivery of the ITZ.
Keywords: Antifungal drugs, Bioassay, Itraconazole, Nanoemulsion, Ocular drug delivery -
Pages 102-108Purposes
Cystic echinococcosis (CE) is a serious contemporary public health problem. Different CE treatment methods are of considerable importance, with albendazole (ABZ) being one of the most preferred drugs for CE treatment and prophylaxis. In this study, we evaluated the nephrotoxicity caused by ABZ and ABZ-loaded solid lipid nanoparticles (SLNs) in mice with experimental hydatid cyst.
MethodsABZ-loaded SLNs were produced by micro-emulsification and a high shear homogenization technique. Thereafter, we evaluated the physicochemical characterization of the product. Live protoscolices were injected into mice to induce experimental hydatidosis. Mice were then treated with ABZ and ABZ-loaded SLNs. The nephrotoxicity effects were evaluated by biochemical and histopathological surveys.
ResultsSignificantly different blood urea nitrogen (BUN) levels were observed between the two infected groups (ABZ treatment and ABZ-loaded SLN treatment) and the control group. The kidney malondialdehyde (MDA) and glutathione (GSH) levels of the infected groups were not significantly different from those of the control group. The histopathological study revealed nephropathic and pathologic changes in the ABZ and ABZ-loaded SLN groups.
ConclusionABZ formulated for ABZ-loaded SLNs had a more prominent chemoprophylactic efficacy on CE and fewer side effects than ABZ alone. Neither ABZ nor ABZ-loaded SLNs caused significant biochemical and histopathological defects on the kidney, and all functional biochemical markers stayed within the normal range. Therefore, ABZ-loaded SLNs could be a potential new product for CE treatment.
Keywords: Albendazole, Nanoparticles, Echinococcus granulosus, Hydatid cyst, Nephrotoxicity -
Pages 109-117Introduction
Insoluble fibronectin as an extracellular matrix (ECM) protein has the potential to promote proliferation, differentiation, and migration of mesenchymal stem cells (MSCs). However, there is limited information about the effects of fibronectin various concentrations on bone marrow-derived MSCs (BMMSCs) function and differentiation.
Materials and MethodsIn this experimental study, using a gel injection device, BMMSCs were encapsulated in sodium alginate microcapsules containing 1.25% alginate, 1% gelatin, and four different concentrations of fibronectin (0.01, 0.05, 0.1, and 0.2 µg/ml). MTT assay was used to examine the proliferation of BMMSCs in des. Also, BMMSCs apoptosis rates were calculated using Annexin-V/PI staining and FACS analysis within 48 hours of exposure. Alkaline phosphatase (ALP) test was conducted to assess BMMSCs osteogenic differentiation. Finally, mRNA expression levels of the SP7, osteocalcin (OCN), Twist Family BHLH Transcription Factor 1 (Twist1), Peroxisome proliferator‐activated receptor γ2 (PPARγ2), Cyclin-dependent kinase 1 (CDK1), and Zinc Finger And BTB Domain Containing 16 (ZBTB16), which involved in MSCs differentiation process were evaluated using Real-Time PCR following exposure with fibronectin 0.1 µg/ml.
ResultAccording to results, fibronectin had the potential to promote proliferation rates of the BMMSCs, in particular at 0.1 and 0.2 µg/ml concentrations. On the other hand, we showed that various concentrations of the fibronectin were not able to modify apoptosis rates of the BMMSCs, negatively or positively. Notable potential of the fibronectin, to trigger osteogenic differentiation of the BMMSCs was documented. Also, RT-PCR results indicated that fibronectin could augment osteogenic differentiation of cultured BMMSCs
ConclusionResults showed that fibronectin can improve proliferation and osteogenic differentiation of BMMSCs without any effect on these cells' survival.
Keywords: Bone marrow-derived MSCs (BMMSCs), Alginate, Fibronectin, Microcapsules, osteogenic differentiation -
Pages 118-127Purpose
Oxidative stress-induced mitochondrial damage is the main event in acquired brain injuries (ABI). This study aimed to evaluate the effects of melatonin, a mitochondria-targeted antioxidant, on mitochondrial and brain injury markers, and the clinical outcomes of patients with ABI.
MethodsIn this randomized controlled trial, intensive care unit (ICU) or neurology patients with ABI (n=60) received melatonin (21 mg/day) or placebo tablets, within the first 72 hours of injury onset for five days. As a primary endpoint, serum levels of malondialdehyde (MDA), S100B and C-reactive protein (CRP) were compared at baseline, and after five days’ intervention. Secondary endpoints included assessment of Glasgow Coma Scale and Sequential Organ Failure Assessment (at the end of day 5), Rancho Los Amigos Revised Scale and modified Rankin Scale (at the end of month 3), the duration of mechanical ventilation, the lengths of ICU and hospital stays, and in-hospital and three-month mortality.
ResultsThere were no significant effects of melatonin on the primary and secondary outcomes. However, the subgroup analysis showed a significant reduction in S100B in patients with non-traumatic brain injuries, receiving melatonin versus placebo (p: 0.016).
ConclusionThis study showed that melatonin supplementation in the early phase of brain injury had no significant effects on the injury markers and clinical outcomes of patients with ABI. However, it reduced the level of S100B in the non-traumatic subgroup. Further larger-scale studies are needed to determine the effects of melatonin on the ABI and its subgroups.
Keywords: Brain injury, Melatonin, Mitochondria, Oxidative stress -
Pages 128-141Purpose
Ovarian carcinoma is one of the gynaecological malignancies that have the highest mortality rates due to its progressivity. Endothelin signalling plays a leading role in the progression of ovarian cancer through Epithelial-to-Mesenchymal Transition (EMT). Cisplatin commonly used as potent chemotherapy; however, its application hindered by its nephrotoxic effect. Curcumin, a turmeric-derived compound, has an anticancer property, as well as a renal protective effect. Moreover, curcumin augments the affinity of the antioxidant enzyme, while inhibits endothelin-1 (ET-1) signalling. The effects of curcumin on ovarian cancer progression and cisplatin-induced kidney injury remain unknown.
MethodsCurcumin was used as a supplementary therapy together with cisplatin in Human Ovarian Cancer Cell line (SKOV3) and also in rodent-induced ovarian cancer. The kidney phenotype in the ovarian cancer rat model after cisplatin ± curcumin administration will also be analyzed
ResultsCo-treatment of cisplatin with curcumin enhanced the expression of a gene involved in apoptosis in association with NRF2 enhancement, thus activated ETBR-mediated ET-1 clearance in SKOV3 cell and ovarian cancer model in rat. Moreover, curcumin treatment improved mitochondria biogenesis markers such as PGC-1α and TFAM and prevented the elevated of ET-1-mediated renal fibrosis and apoptosis in kidney isolated from cisplatin-treated ovarian cancer rat.
ConclusionCurcumin could be potentially added as an anticancer adjuvant with protective effects in the kidney; thus, improves the efficacy and safety of cisplatin treatment in the clinical setting.
Keywords: Ovarian Cancer, Curcumin, Endothelin-1, ETBR, NRF2, Cisplatin-induced kidney injury -
Pages 142-154Purpose
Recently, bone tissue engineering as a new strategy is used to repair and replace bone defects due to limitations in allograft and autograft methods. In this regard, we prepared nanofibrous scaffolds composed of polycaprolactone and magnesium oxide nanoparticles using the electrospinning technique for possible bone tissue engineering applications.
MethodsThe fabricated composites were characterized via scanning electron microscopy imaging of scaffolds and seeded cells, water contact angle, DAPI staining, and MTT assay. Then osteogenic differentiation of adipose-derived mesenchymal stem cells cultured on this composite scaffold was determined by standard osteogenic marker tests, including alkaline phosphatase activity, calcium deposition, and expression of osteogenic differentiation genes in the laboratory conditions.
ResultsThe Scanning electron microscopy analysis demonstrated that the diameter of nanofibers significantly decreased from 1029.25±209.349 µm to 537.83+0.140 nm, with the increase of MgO concentration to 2% (p<0.05). Initial adhesion and proliferation of the adipose-derived mesenchymal stem cells on magnesium oxide/polycaprolactone scaffolds were significantly enhanced with the increasing of magnesium oxide concentration (p<0.05). The 2% magnesium oxide/polycaprolactone nanofibrous scaffold showed significant increase in ALP activity (p<0.05) and osteogenic-related gene expressions (Col1a1 and OPN) (p<0.05) in compared to pure polycaprolactone and (0, 0.5 and 1%) magnesium oxide/polycaprolactone scaffolds.
ConclusionAccording to the results, it was demonstrated that magnesium oxide/polycaprolactone composite nanofibers have considerable osteoinductive potential, and taking together adipose-derived mesenchymal stem cells-magnesium oxide/polycaprolactone composite nanofibers can be a proper bio-implant to usage for bone regenerative medicine applications. Future in vivo studies are needed to determine this composite therapeutic potential.
Keywords: Adipose-derived stem cells, Electrospinning, Magnesium oxide, Osteogenesis, Polycaprolactone, Tissue engineering -
Pages 155-162Purpose
During cancer growth, hypoxia occurs along with autophagy as an adaptive responseto overcome cellular stress. Geraniol (GE) is a natural isoprenoid known for its wide anticanceractivity and autophagy induction in the cancer cell. To investigate the antihypoxic potential ofGE with the incidence of autophagy and apoptotic cell death in A549 CoCl2 treated cells.
MethodsA549 cells were incubated for 24 hours with GE and CoCl2 either alone or incombination. We examined the cytotoxicity and cell viability of GE either alone or incombination therapy using MTT and trypan blue assay.GE modulating effect was determined onlipid peroxidation, antioxidant capacity markers, gene expression levels of hypoxia induciblefactor-1 (HIF-1), NF-κB, vascular endothelial growth factor (VEGF), autophagy factors in differentgroups, besides apoptotic bodies using acridine orange/ethidium bromide (AO/EB).
ResultsGE and CoCl2 combination therapy downregulated the expression of HIF-1α thatsuppressed A549 cell growth through downregulation of BNIP3 and beclin-1 gene expression.This resulted in autophagy and apoptotic cell death, in addition to the downregulation of NF-kBand VEGF expression. Also, GE treatment significantly reduced the oxidative stress markers andrestored the antioxidant capacity.
ConclusionGE possesses an antihypoxic effect on A549 CoCl2 treated cells and induces celldeath via autophagy along with apoptosis through HIF-1α/BNIP3/beclin-1 signaling pathway.
Keywords: Hypoxia, Geraniol, HIF-1α, Autophagy, BNIP3, Beclin-1, VEGF -
Pages 163-168Purpose
This study aims to evaluate the role of high-sensitivity troponin T (hsTnT) as a complementary tool for determining cardiotoxicity in non-Hodgkin lymphoma (NHL) patients receiving cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) regimen chemotherapy.
MethodsWe included 35 patients diagnosed with NHL who received CHOP chemotherapy. Left ventricular ejection fraction (LVEF) and hsTnT were measured at two time points: before the first cycle (pre-test) and after the fourth cycle (post-test). The LVEF and hsTnT were analysed using IBM SPSS version 24 through the paired-sample T-test, Wilcoxon signed-rank test, Pearson’s correlation and Spearman’s correlation.
ResultsThere was a significant difference in both LVEF and hsTnT between pre-chemotherapy and post-4th chemotherapy cycles (p = 0.001). However, more contrast difference from the baseline value of hsTnT compared to LVEF could be observed. LVEF did not detect any deterioration in myocardial function. However, 10 out of 35 subjects exhibit hsTnT higher than the 99th percentile of the population (>14 pg/ml), suggesting that myocardial injury (MI) could be detected. There was no correlation between LVEF and hsTnT (p > 0.05).
ConclusionHsTnT, together with LVEF, could complement each other and offer better coverage for detecting cardiotoxicity during the administration of CHOP in NHL patients. An insignificant correlation between hsTnT and LVEF showed that cardiotoxicity existed in a broad spectrum including cellular damage and functional impairment, as hsTnT represents cellular damage, and LVEF reflects heart functional capacity.
Keywords: Cardiotoxicity, Doxorubicin, Left ventricular function, Non-Hodgkin lymphoma, Troponin T, Cancer -
Pages 169-175Purpose
microRNA‐193a‐5p is one of the well-known tumor suppressor miRNAs in the body but in many cases, its expression became reduced in patients suffering from gastric cancer (GC). The main purpose of this study was to restore the function of this miRNA in human GC cells and investigating the effects of enhanced expression of miR‐193a‐5p on proliferation, apoptosis, and migration of GC cells upon in vitro transfection.
MethodsThe KATO III gastric cancer cells were treated with 100 nM of miR‐193a‐5p or negative control sequences. Following that, the MTT assay, flow cytometry assay, and wound-healing assay were applied to estimate the impacts of enhanced expression of this miRNA on the viability, apoptosis, and migration rate of the cells, respectively. Moreover, the total RNA was isolated and alterations in the mRNA expression ratio of migratory genes were measured by qRT-PCR techniques.
ResultsThe findings designated that enhanced expression of miR‐193a‐5p suppressed the migratory ability of the cells, but had no significant effects on cell survival or apoptosis of the transfected cells. In addition, this inhibitory function of miR‐193a‐5p on the migration rate of the KATO III cell line occurs with concurrent suppression of vimentin and MMP-9 gene expression.
ConclusionIt can be concluded that miR‐193a‐5p negatively influences the migratory ability of the cancerous cells and restoring its effects can be regarded as a promising target of future therapeutic interventions, especially for GC metastasis.
Keywords: miRNA-193a‐5p, Gastric Cancer, Gene Therapy, Apoptosis, Migration Assay -
Pages 176-182Purpose
Diabetes mellitus, especially type 2, is conceived as a devastating chronic metabolic disease globally. Due to the existence of an extensive vascular network in the pulmonary tissue, it is suggested that lungs are sensitive to the diabetic condition like other tissues. This study was designed to address the possible effect of type 2 diabetes mellitus on the promotion of pathological changes via vascular injury.
MethodsSixteen male Wistar rats were randomly allocated to the two of Control and T2D groups. To induce type 2 diabetes, rats were received high-fat and a single dose of STZ. On week 12, rats were euthanized and lungs samples were taken. Using Hematoxylin and Eosin staining, the pathological changes were monitored. The expression of vascular ICAM-1 and VCAM-1, and IL-10 was monitored using real-time PCR assay. The level of TNF-α was detected using ELISA assay. Nitrosative stress was monitored using the Griess assay.
ResultsPathological examination in bronchoalveolar discharge revealed the existence of mild to moderate interstitial bronchopneumonia and increased neutrophilic leukocytosis compared to the control. Enhanced ICAM-1 and VCAM-1 expression and suppression of IL-10 was found using real-time PCR analysis (p<0.05). The levels of TNF-α and NO were increased with diabetic changes compared to the control rats (p<0.05).
ConclusionT2D could promote pulmonary tissue injury via the production of TNF-α and up-regulation of vascular ICAM-1 and VCAM-1. The inflammatory status and vascular ICAM-1 and VCAM-1 increase immune cell recruitment into the pulmonary niche.
Keywords: Type 2 Diabetes Mellitus, Lungs, Vascular Cell Adhesion Molecules, Inflammation, Nitrosative Stress -
Restoration of miRNA-143 Expression Inhibits Growth and Migration of MKN-45 Gastric Cancer Cell LinePages 183-190Purpose
Gastric cancer (GC) is one of the main causes of death from diseases, especially in developing countries. MicroRNAs (miRNAs) are important modulators of the messenger RNAs expression. Among these miRNAs, MiR-143 is a tumor suppressor miRNA and its irregular expression has been revealed in a diversity of malignancies such as GC.
MethodsIn this study, we have attempted to restore the miR-143 expression in MKN-45 cells by introducing pCMV-miR-143 plasmid vectors. The consequences of exogenous expression of miR-143 on cell proliferation and migration were assessed by MTT and scratch tests, respectively. In addition, the DAPI staining assay was applied for apoptosisquantification. Following miR-143 transfection, the changes in K-Ras, C-Myc, MMP9, Bax, Caspase-3, and Caspase-9 mRNA levels were assessed.
ResultsThe results indicated that the enhanced expression of miR-143 had negative effects on MKN-45 cells proliferation and invasion. Moreover, decreased expressions of K-Ras, MMP9, and C-Myc and up-regulation of Bax, Caspase-3, and Caspase-9 as downstream targets of miR-143 were recognized.
ConclusionThese experimental results indicate that reversing the miR-143 expression, by novel techniques, including miRNA replacement could be considered as an efficient approach to reduce cell survival and metastasis.
Keywords: Gastric Cancer, miR-143, Replacement Therapy, Proliferation, Apoptosis, Migration Ability -
Pages 191-199Purpose
Centrosomal protein 55 (CEP55) is a pivotal protein for cytokinesis during cell division. This study aimed to provide a comprehensive information about the CEP55 gene, including its expression pattern in several cancer types, conduct functional domain analysis across species, and perform a computational approach for potential inhibitors of CEP55.
MethodsThe expression levels of CEP55 in different cancers were analyzed using the Oncomine and TCGA databases. Evolutionary analysis of the CEP55 gene in various species was performed using MEGA-X software. Molecular docking analysis was used to screen the binding affinity of several natural products on CEP55–ALIX binding interaction.
ResultsHigh CEP55 expression was observed in 16 datasets of different cancer types. The high expression of the CEP55 protein was associated with worse outcomes in cancer treatments. Phylogenetic and evolutionary analyses revealed that the amino acid residues essential for CEP55 binding and localization were mostly conserved across vertebrates. Seventeen plant-based compounds were docked against the CEP55 protein to determine their binding affinities and illustrated specific sites of interaction for predicting novel protein–drug interactions. Flavanol compounds epigallocatechin gallate and catechin possessed superior binding affinity to all other compounds owing to the substitution of gallic ester or hydroxyl groups on the C3 position.
ConclusionThis study provides comprehensive information about the CEP55 gene and insights for designing potent inhibitors against CEP55 signaling.
Keywords: Anticancer, Evolutionary analysis, Molecular docking, CEP55 inhibitor, Natural product -
Pages 200-205Purpose
Non-alcoholic steatohepatitis (NASH) is an inflammatory disorder and an aggressive form of fatty liver disease. Certain microRNAs, including miR-122, 21, 34a, and 451, are involved in the transition from steatosis to NASH. This study examined how trans-chalcone (the core of chalcone derivatives) affects NAFLD progression by regulating miRNAs.
MethodsMale rats were divided into three groups (n = 7/group) as follows: control, rats were gavaged with 10% tween 80 (for two weeks); NASH, rats were gavaged with a high-fat liquid diet (HFD; for six weeks) and 10% tween 80 (for two weeks); NASH + Chal, rats were gavaged with the HFD (for six weeks) and trans-chalcone (for two weeks). Hepatic expression levels of miR-122, 21, 34a, and 451 were determined.
Resultstrans-Chalcone reversed histological abnormalities, reduced liver injury markers, and attenuated insulin resistance in HFD-fed rats. In the liver, HFD-induced NASH increased the expression level of miR-34a and decreased expression levels of miR-122, 21, and 451. However, trans-chalcone inhibited HFD-induced changes in expression levels of these miRNAs.
Conclusiontrans-Chalcone could inhibit the transition from steatosis to NASH through the modulation of miR-122, 21, 34a, and 451 expression levels in the liver.
Keywords: Non-alcoholic steatohepatitis, trans-Chalcone, miRNAs, Liver, Rat