seyed ali ziai

Nanoliposomes are spherical nano-sized capsules enclosed by lipid membranes, serving as a biocompatible vehicle to enhance the delivery of therapeutic agents.The objective of this research is to prepare and characterize nanoliposome-encapsulated auraptene and compare its cytotoxic and anti-angiogenic effects to non-liposomal auraptene .

Liposomal auraptene was formulated using DSPC/ DSPG/ Cholesterol (molar ratio of 4:1:2) in combination with two different molar ratios of auraptene (0.1 and 0.05). The entrapment efficiency was evaluated using High-Performance Liquid Chromatography (HPLC). Various parameters, including Dynamic Light Scattering (DLS), zeta potential, stability, and release kinetics, were investigated. Subsequently, both liposomal and non-liposomal auraptene, along with bare liposomes, were applied to the MDA-MB-231 cell line for duration of 72 hours at 37°C at varying concentrations. Cytotoxicity was assessed using the MTT assay. Additionally, the study examined the anti-angiogenic effects on the vessels in the chorioallantoic membrane of chick embryos .

The entrapment efficiency of auraptene was found to be satisfactory at 50%. The liposome size ranged from 85 to 241 nm, with a Z-Average of 190.9 nm. The zeta potentials for all formulations were consistently around -55.7, and the Polydispersity Index (PDI) was less than 0.3 for all formulations. The release profile demonstrated approximately 80% drug release over a period of 130 hours. Notably, liposomal auraptene exhibited a significantly lower IC50 value (38.61 (95% Confidence Interval: 30.56 to 48.78)) compared to non-liposomal auraptene (50.36 (95% Confidence Interval: 43.58 to 58.19)) (p = 0.0240).

Moreover, the administration of 2.5 and 5 μM of liposomal auraptene led to a reduction in the vessels within the chorioallantoic membrane at the injection site when compared to the control group.In summary, the use of biodegradable nanoliposomal carriers improved the solubility, release profile, and stability of auraptene while demonstrating anticancer and anti-angiogenic properties.

Breast cancer is a highly common cancer that affects women worldwide. Different forms of breast cancer are currently treated using various strategies. One successful avenue in cancer therapy involves targeting anti-angiogenic factors. Extensive evidence supports the idea that umbelliprenin, a natural compound derived from plant species, possesses anti-cancer properties. In this research, we investigated the impact of umbelliprenin on the PI3K/AKT/mTOR and PI3K/AKT/MAPK signaling pathways, along with their downstream products HIF-1α/VEGF, within the T47D cell line. We assessed the cytotoxic effects of umbelliprenin on T47D cell lines using the MTT method. Non-toxic concentrations, specifically IC5 and IC10 of umbelliprenin, were selected to investigate the effects on the signaling pathways. For T47D cells stimulated by EGF and cobalt chloride (CoCl2), we measured the mRNA levels of EGFR, PI3K, AKT, mTOR, S6K, HIF-1β, HIF-1α, VEGF, VEGFR, ERK1/2, and 4EBP1 using Real-time PCR. Additionally, we examined VEGF and HIF-1α protein expression through Western blot analysis. We determined that the IC5 and IC10 concentrations of umbelliprenin were 10 and 20 µM, respectively, using the MTT method. Umbelliprenin significantly reduced the expression of VEGF and HIF1-α proteins in cells stimulated with EGF and CoCl2. It also led to a decrease in the mRNA levels of EGFR, PI3K, VEGF, mTOR, HIF1-α, HIF-1β, S6K, ERK2, and ERK1. The results of this study indicated that umbelliprenin, functioning as a cytotoxic agent, inhibits the PI3K/AKT/mTOR and PI3K/AKT/MAPK signaling pathways in T47D cells induced by EGF and CoCl2.

Pharmacology, as a major field in medical education, significantly shapes the competency of future healthcare professionals. The necessity of familiarizing with new teaching methods in pharmacology and evaluating their outcomes can be a good idea for their implementation. This article investigated the teaching of pharmacology in many medical universities worldwide with geographical diversity and international rankings to determine the reasons for using specific methods in those universities and to identify the results of the evaluations of their implementation.

In this descriptive study, universities were selected from all international rankings and geographical diversity to have more diverse data. Several countries and universities from each continent were chosen, and among neighboring countries, universities with social and cultural conditions closer to Iran were selected. The teaching method of each university was examined by visiting the university's website or studying an article about that method in the university or by contacting the head of the pharmacology department to review and summarize its advantages and disadvantages.

The methods of teaching pharmacology and their evolution in the examined faculties have been categorized.

It seems that a change in the traditional method is inevitable, and while teaching basic pharmacology may still require a traditional approach, clinical pharmacology discussions require the use of different methods. It also appears necessary for pharmacology to be taught both in the basics and in clinical settings, applying a different approach to teaching these two aspects.

The landscape of teaching basic and clinical sciences in medical schools has undergone significant changes in recent decades. Pharmacology, as one of the pivotal medical courses and a key therapeutic tool with unique features such as extensive scope and the necessity of comprehensive learning by students, is considered among the most prominent medical courses. Each medical school must ensure that its graduates have thoroughly learned this course and have acquired the skills to recognize and apply this knowledge in patient treatment effectively. In this regard, we aimed to identify and critique the existing pharmacology teaching methods to propose optimal approaches.

This article utilized conventional teaching methods as keywords, focusing on pharmacology. A review of published articles on medical databases such as PubMed and Science Direct, and finally Google Scholar, along with an exploration of information available on university websites, formed the basis of the study. Teaching methods, along with their advantages and disadvantages, were elucidated.

Among the six conventional teaching methods in medicine, traditional teaching, characterized by didactic lectures, remains the oldest and is widely employed in many universities globally. Subsequent newer methods, such as problem-based learning and case-based learning rooted in clinical experiences, are variably adopted by universities worldwide, each with its unique ranking. Question-based learning and multidisciplinary learning also demonstrate potential, though their implementation is somewhat more complex and requires robust support.

The dynamic landscape of medical pharmacology education reveals a diverse array of teaching methods, each with its distinctive features and noteworthy points. Traditional lecture-based approaches provide a foundational structure, linking theoretical concepts with experiential learning and fostering collaborative models, teamwork, and comprehensive patient care. Meanwhile, technology-enhanced strategies cater to the needs of the digital generation. The efficacy of each method is context-dependent, influenced by geographical location, cultural factors, and the developmental stage of each method.

Triple-negative breast cancer is a significant global health challenge, and there's growing interest in targeting multiple pathways for treatment. Umbelliprenin, derived from herbal sources, has shown anti-tumor potential. This study aimed to assess umbelliprenin's impact on key genes related to proliferation, metastasis, and angiogenesis.

Umbelliprenin, which was synthesized by the Pharmaceutical Research Center (PRC) at Mashhad University of Medical Sciences in Iran, was utilized in this study. The study aimed to investigate the impact of umbelliprenin on EGF and CoCl2-induced signaling in the PI3K/AKT/mTOR and MAPK pathways. Quantitative PCR was employed to assess the expression of EGFR, PI3K, AKT, mTOR, S6K, ERK1, ERK2, 4EBP1, HIF-1α, HIF-1β, VEGF, and VEGFR genes. Additionally, immunoblot assays were conducted to evaluate the levels of VEGF and HIF-1α in MDA-MB-468 cells.

The study found that umbelliprenin had cytotoxic effects, with an IC50 value of 152.5 μM. At concentrations of 10 μM and 20 μM, it upregulated genes like EGFR, VEGFR, HIF-1α, VEGF, PI3K, ERK2, and mTOR while downregulating 4EBP1. Umbelliprenin also increased VEGF protein levels. When used on EGF-stimulated cells, it enhanced VEGF and PI3K expression while inhibiting AKT, ERK2, mTOR, and antiproliferative 4EBP1 genes. Notably, VEGF and HIF-1α protein levels remained unchanged. Conversely, umbelliprenin downregulated EGFR, AKT, ERK1/2, HIF-1α, and VEGF in CoCl2-stimulated cells, while elevating 4EBP1 and reducing VEGF and HIF-1α protein levels.

Umbelliprenin inhibited MDA-MB-468 cell growth and impacted gene expression related to metastasis and angiogenesis, particularly under conditions of EGFR activation and hypoxia.

Angiotensin-converting enzyme (ACE) plays a pivotal role in the production of angiotensin II and the inactivation of bradykinin. Recent studies have suggested that human serum albumin may possess ACE-inhibitory properties, serving as a potential endogenous ACE inhibitor that primarily affects serum ACE levels. Interestingly, the infusion of albumin in the postoperative phase of cardiac surgery has been associated with the development of hypotension.

This study aimed to assess serum ACE activity in 27 hypoalbuminemia patients admitted to the ICU before and after a protein-rich diet was administered to raise their serum albumin levels. Serum ACE activity was quantified using raas(HPLC), measuring the formation of hippuric acid, a product generated during the incubation of serum with Hip-His-Leu, a substrate, at 37°C for 30 minutes.

In vitro experiments demonstrated that the addition of albumin to human sera led to a significant reduction in ACE activity compared to control groups (P < 0.0001). This reduction was consistent across all serum samples. Specifically, the maximum velocity (Vmax) of ACE activity significantly decreased from 14.90 U/L in the control group to 3.210 U/L in the albumin-added group (P = 0.0262). Notably, there was no significant change in the Michaelis constant (Km) between the control group (0.5263 mM) and the albumin group (0.2742 mM) (P = 0.6763), indicating a non-competitive inhibitory effect of albumin on ACE activity. Interestingly, in this study, elevating serum albumin levels in hypoalbuminemia patients following a protein-rich diet resulted in both ACE inhibition and a slight increase in activity (P = 0.0201). This increase correlated mildly with serum albumin levels across all samples.

In conclusion, contrary to in vitro findings, raising serum albumin levels in hypoalbuminemia patients did not further inhibit serum ACE activity.

Breast cancer is known to be one of the most prevalent malignancies in women worldwide. Umbelliprenin (UMB) is a naturally-occurring component derived from plant species, which has shown anticancer properties. The present study aimed to evaluate the effect of UMB on the PI3K / Akt / ERK signaling pathway and their products HIF-1α / VEGF in the MDA-MB-231 cell line.
In this experimental study, the cytotoxic effect of UMB on MDA-MB- 231 cells was evaluated using the MTT assay and the UMB concentrations of IC5 and IC10 were selected for the signaling pathway study. MDA-MB-231 cells were stimulated with EGF and CoCl2 and UMB IC5 and IC10 effects on gene expression and translation was studied. PI3K / Akt / mTOR / S6K / Erk1 and 2 / 4E-BP1 / HIF-1α / HIF-1α/ EGFR / VEGFR and VEGF mRNA expression, and VEGF / HIF-1α proteins were evaluated employing real time polymerase chain reaction and western blot analysis, respectively.
The concentrations of UMB in IC10 and IC5 were 20 and 10 μM, respectively. UMB, specifically IC10, significantly inhibited PI3K, ERK1, ERK2, Akt, mTOR, HIF1-α, HIF1-β mRNA, as well as HIF-1α and VEGF protein expression.
Our results suggested that UMB, a cytotoxic agent, inhibits PI3K / Akt / ERK signal pathway in the CoCl2 or EGF-stimulated MDA-MB-231 cells.

Macrophages play an important role in tumor growth (M2 macrophage) or suppression (M1 macrophage). Auraptene, a prenyloxycoumarin compound extracted from Citrus plants, has anti-cancer and anti-inflammatory properties. The purpose of this study was to look into the effect of auraptene on macrophage polarization and the tumor microenvironment when a human monocyte cell line (THP-1) was co-cultured with human colorectal adenocarcinoma (HT-29). The toxicity of auraptene on THP-1 and HT-29 cells was determined by the MTT method. Using flow cytometry, the effect of auraptene on macrophage polarization was studied through THP-1 as a macrophage source. The effect of auraptene on the macrophage population was also studied in THP-1 co-cultured with HT-29. Furthermore, macrophage function was assessed by measuring IL-10 and IL-12 concentrations using the ELISA method, nitric oxide (NO) concentrations using the Griess method, and HT-29 apoptosis by flow cytometry. The M1/M2 ratio of THP-1 exposed to auraptene increased significantly in both naive THP-1 and THP-1 co-cultured with HT-29. Auraptene significantly reduced tumor-protective IL-10 secretion in M1 (p=0.0032) and M2 (p=0.0011). Auraptene increased anti-tumor IL-12 in M2 significantly (p=0.0011). It increased M1 NO production (p=0.0236) while decreasing M2 NO production (p=0.0001). Auraptene also increased HT-29 apoptosis in M0 and M1 co-cultures (p<0.0001). Auraptene altered the release profiles and macrophage types to enhance the suppression of HT-29 cells.

In this study, we evaluated the effects of nanofiber and film polymers with doxycycline for treating a wound in a diabetic rat model. 108 male rats were divided into six groups, the control group, the diabetic control, and the groups were diabetic rats receiving different wound dressing. At the 3rd, 7th, and 14th days, macroscopic/histologic imaging and tissue sampling were performed. Tissues were analyzed for IL-1β, TNF-α, IL-10, TIMP-1, and MMP-2 by using ELISA. Dressings of chitosan, polyvinyl alcohol and doxycycline increased the rate of wound closure, the volume of collagen, dermal, and epidermis; in addition, it increased the number of fibroblasts and basal cell epidermis cells, vascular length, and decreased the number of neutrophil cells. Inflammatory cytokines and MMP-2 were decreased, and anti-inflammatory IL-10 and TIMP-1 were increased. It was ultimately attained that the combination of chitosan/ polyvinyl alcohol /doxycycline could be a useful dressing for the healing of diabetic wounds.

Umbelliprenin, a prenylated coumarin from different species of Ferula, has demonstrated anti-cancer effects in various types of cancer cells, but the potential molecular mechanisms for the anti-angiogenic activity of umbelliprenin in breast cancer cells have not yet been studied.  In this study, we investigated the possible molecular pathways involved in the anti-angiogenic effect of umbelliprenin in EGF and CoCl2 stimulated SKBR-3 breast cancer cells.

Effects of umbelliprenin on the changes in EGFR signaling genes (EGFR, PI3K, AKT, mTOR, S6K, 4EBP1, ERK1/2, HIF-1α, HIF-1β, VEGF, VEGFR) and proteins (VEGF/HIF-1α) expression were assayed in SKBR-3 via Quantitative PCR and Western blotting assays.

Umbelliprenin dramatically decreased the living cells in a concentration related manner (IC50=103.9 µM) and non- toxic doses of umbelliprenin IC5 and IC10 (10 and 20 µM, respectively) were used for evaluating in vitro anti-angiogenic effects. Umbelliprenin significantly reduced pro-angiogenic AKT, ERK1, ERK2, mTOR, S6K, HIF-1α, HIF-1b, VEGF and VEGFR mRNAs in EGF-treated, and  AKT, ERK2, S6K, HIF-1α, HIF-1b, VEGF and VEGFR mRNAs in CoCl2-treated cells. Umbelliprenin significantly increased anti-angiogenic 4EBP1 mRNA in EGF / CoCl2-treated cells. It significantly decreased the levels of HIF-1α and VEGF proteins, in CoCl2-treated cells.

Our findings showed that umbelliprenin exhibits anti-angiogenic effects by decreasing the expression of AKT/mTOR/MAPK angiogenesis pathways in EGF or CoCl2 treated SKBR-3 breast cancer cells.

The stimulator of interferon genes (STING) agonist (cGAMP) kills the cancer cells through the activation of the innate immune system. PC3 cells are high in BTK and low in STING. In this study, the effect of adding STING agonist, cGAMP, to docetaxel investigated.

 PC3 cells were treated with docetaxel, cGAMP, and a combination of the docetaxel and cGAMP. Cell toxicity was evaluated by MTT assay, and changes of STING, IRF3, BTK, and DDX41 genes’ expression were quantified by the real-time PCR. STING protein was also detected by Western blotting.

 The IC50 of docetaxel was 31.1 nM, and cGAMP did not change it significantly but decreased docetaxel toxicity about 30%. Docetaxel increased IRF3, BTK, and DDX41 gene expression significantly, and STING protein about 5 folds. By adding cGAMP to docetaxel STING, IRF3, and BTK, expression decreased several folds.

 In this in vitro study, cGAMP potentiated docetaxel’s effects and alleviated it.

The COVID-19 pandemic is a global health emergency caused by SARS-CoV-2. Unfortunately, no effective drugs have been found to date. There is also a major need for new therapies to treat this disease. The main protease is an attractive drug target among coronaviruses due to its important role in the processing of viral RNA-translated polyproteins. Objective of This study was conducted to screen data-bases of herbal compounds for potential main protease inhibitors.

Natural products from 3 database banks were first tested and filtered by ADME / toxicity, then their molecular energy was minimized, and finally, they were docked into the SARS-CoV-2 main protease and compared with indinavir.

The binding energies of 6570 molecules from different herbal compounds comprising databases were tested and five of the molecules with the highest binding energies for SARS-CoV-2 main protease docking were selected and key interactions were studied.

In conclusion, five herbal compounds including Sodwanone B, Cyclo-mulberrin, and a glycosylated derivative of kaempferol had lower docking energy com-pared to indinavir and were suggested for further research.

A cluster of pneumonia cases of unknown origin was detected on December 31th which led to the discovery of coronavirus disease 2019 (COVID-19). Lungs are the primary site of involvement. SARS-COV-2, which is the causative agent, enters the alveolar cells using ACE2 as a receptor. Due to exposure of first cases to Wuhan’s animal market, a zoonotic transmission was suspected. Further studies suggested human to human transmission through contact and droplets. Symptoms vary from asymptomatic to acute respiratory distress syndrome and death. Cases are diagnosed based on clin-ical and laboratory findings. Currently, there is no definitive treatment or vaccine and different antiviral and other treatments are being tested as possible therapeutic agents with different mechanisms, for example, Chloroquine, hydroxychloroquine, azithromy-cin, favipiravir, umifenovir, ribavirin, Ivermectin, etc.

Poisoning is one of the important social problems in developing coun-tries, and acute poisoning due to suicide by drug overdose or toxins is one of the most common cases of poisoning that requires emergency care. This study was aimed to determine the demographics of benzodiazepines poisoned patients in one of the refer-ral centers for poisoning in Iran.

This cross-sectional study was conducted on patients who referred to the poisoning emergency ward of Loghman Hakim Hospital from April 2015 to March 2016. Among 10624 patients who referred to the hospital at the study period, 2543 of them were poisoned by benzodiazepines. A total of 263 patients were selected randomly and were assessed for age, gender and the type of the benzodiazepine. The data were analyzed by version 15 of SPSS software.

Among 263 patients, 127 were males (48.2%) and 136 were females (51.7%). The mean age of patients was 31 years old with a range of 13 – 80 years old. In addi-tion, most patients were in the age of between 18 to 35 years (n = 152). In this study, 91 patients (34.6%) were single-drug poisoned with benzodiazepines and 172 cases (65.4%) were poisoned by multi-drug regimens including benzodiazepines. Between different types of benzodiazepines, the most common type was Alprazolam and the least common benzodiazepine was Oxazepam. Almost 96% of patients (n = 252) were treated successfully and 8 patients (3%) got discharged with self-consent. Further-more, the mortality rate was approximately 1% (n = 3).

Benzodiazepines poisoning is common in younger patients; thus, close attentions are needed for the prescription of these drugs in young patients. Considering easy access to benzodiazepines in the community, periodic visits to psychiatrists may be useful for the reduction of benzodiazepine poisoning.

Leishmaniasis is the most important parasitic disease in Iran and is the third highest rate of rural cutaneous leishmaniasis in the world. Chitosan-polyethylene oxide nanocomposite fibers can be a suitable replacement for ordinary bandages. For the first time, in the absence of any published reports, the present in vitro study aimed to evaluate the anti-leishmanial effects of chitosan (CS)-polyethylene oxide (PEO)-berberine nanofibers on Leishmania major. The present experimental study was conducted in 2018 in Tehran, Iran. The CS-PEO nanofibers containing berberine, as a natural anti-parasitic agent, were prepared using the electrospinning technique. Biocompatibility and fibroblast proliferation on nanofibers were investigated. In addition, the anti-leishmanial activity of CS-PEO nanofibers in both the promastigote and amastigote stages of Leishmania major was evaluated after parasite vital staining and MTT assay and compared to a control group. Statistical analysis was performed using SPSS software (version 18.0). Statistically significant differences were determined using the one-way ANOVA. The Duncan and Dunnett post hoc tests were used for within-group comparisons. P<0.05 was considered statistically significant. The results showed that nanofiber scaffolds with a mean diameter of 77.5±19.5 nm were perfect, regular, bead-free, and non-toxic, on which fibroblast cells grew well and proliferated. In addition, the optical density indicated that berberine 20% (w/v) significantly prevented promastigotes growth (IC50=0.24 μg/mL) and amastigotes death (IC50=0.91 μg/mL) compared with other concentrations and the control group. The study on the cytotoxic effects showed that CS-PEO-berberine nanofibers had strong lethal effects on Leishmania major in promastigote and amastigote stages in vitro. Further studies are required to investigate the effects of this nanofiber on leishmanial ulcers in laboratory animals and clinical cases.

Rapid healing of cutaneous leishmaniasis as one of the most important parasitic diseases leads to the decrease of scars and prevention of a great threat to the looks of the affected people. Today, the use of nano-scaffolds is rapidly increasing in tissue engineering and regenerative medicine with structures similar to the target tissue. Chitosan (CS) is a bioactive polymer with antimicrobial and accelerating features of healing wounds, which is commonly used in biomedicine. This study aimed to investigate the effects of CS/polyethylene oxide (PEO)/berberine (BBR) nanofibers on the experimental ulcers of Leishmania major in BALB/c mice. CS/PEO/BBR nanofibers were prepared by the electrospinning method, and their morphology was examined by SEM, TEM, and AFM. Then, water absorption, stability, biocompatibility, porosity, and drug release from nano-scaffolds were explored. Afterward, 28 BALB/c mice infected with the parasite were randomly divided into control and experimental groups, and their wounds were dressed with the produced nano-scaffolds. Finally, the effect of nanobandage on the animals was investigated by macroscopic, histopathologic, and in vivo imaging examinations. The prepared nanofibers were completely uniform, cylindrical, bead-free, and biocompatible with an average diameter of 94±12 nm and had appropriate drug release. In addition, the reduced skin ulcer diameter (P=0.000), parasite burden (P=0.003), changes in the epidermis (P=0.023), and dermis (P=0.032) indicated significantly strong effectiveness of the produced nano-scaffolds against leishmania ulcers. Studies showed that CS/PEO/BBR nanofibers have a positive effect on the rapid healing of leishmania ulcers. Future studies should focus on other chronic ulcers treatment.

This study aimed to investigate the protective effect of Gallic acid (GA) on the cyclophosphamide (CP) toxicity induced in the reproductive system.

After a pilot study for dose responses of gallic acid, forty adult male NMRI mice were divided into 5 groups (n=8): control, sham (NaCl Serum: 0.2mL per day), CP (15 mg kg1- per week; IP), GA (12.5 mg kg1- per day ; IP) and GA (12.5 mg kg1- per day ; IP) +CP(15 mg kg1- per week; IP). After treatment, the left testis was detached and used for histological examination and right testis used for malondialdehyde (MDA) measures. Left caudal epididymis was placed in the Ham’s F10 medium and released spermatozoa were used in order to analyze sperm parameters. Sperm DNA fragmentation was assessed by Sperm Chromatin Dispersion (SCD) method.

In the CP group, there was a significant increase in the sperm DNA fragmentation (% 23.91 ± 57.89) compared with control group (% 10.27 ± 24.52). That was significantly improved by GA (12.5 mg kg1- per day ; IP) in GA+CP group (% 8.85 ± 28.4) compared to CP group (p< .001). A significant increase was reported about MDA levels in CP group (2.59 ± 6.26) in compared with the control group (2.05 ± 4.30), But GA (1.33 ± 3.24) decreased it in GA+ CP group (p< .01). The histopathological investigation revealed marked testicular atrophy in CP group, whereas GA diminished these deviations (P< .05).

Gallic acid can modify the reproductive toxicity of cyclophosphamide in NMRI mice and increase the antioxidant capacity of testis tissue.

This study aimed to use a valid mouse model of chronic stress like a maternal separation (MS) to determine the effect of early life chronic stress on oocyte quality and subsequent in vitro embryo development.

This study was based on case-control, interventional, and quantitative applied research. Mice were subjected to 180 minutes of MS stress paradigm at postnatal day (PND) 2–14. Then, corticosterone and serotonin levels were measured in the serum and ovary samples, respectively. In addition, relevant behavioral tests including an elevated plus maze (EPM) and open field test (OFT) were performed for evaluating anxiety-like behaviors at PND 48. Finally, oocyte number, nuclear maturation, reactive oxygen species (ROS) and intracellular glutathione (GSH) levels, as well as in vitro embryo development were evaluated as well.

Our findings showed that MS provokes anxiety-like behavior and increases serum corticosterone concentration (P < 0.05). On the other hand, the number of oocytes (P < 0.001), nuclear maturation (P < 0.05), and the concentration of ovarian serotonin (P < 0.01) decreased following MS. Further, the fertilization (P < 0.001) and blastocyst rate (P < 0.05) significantly decreased in MS mice. Eventually, chronic stress led to a reduction in the level of GSH (P < 0.01) while it increased the level of ROS production (P < 0.001).

Chronic stress through, at least in part, oxidative stress in the oocytes of mice undergoing MS paradigm negatively affected the oocyte competency and embryo development.

Design and construction of biocompatible and biodegradable scaffolds are among the main goals of tissue engineering. Recently, use of nano-hydroxyapatite as a bioactive bioceramic agent with high similarity to the mineral phase of the human bone tissue, in combination with biodegradable polymers and implant coatings has attracted the attention of researchers in the field of biomaterial sciences. The present study aimed to assess the differentiation of bone marrow stromal cells (BMSCs) in osteoblast-like cells on the chitosan/polyethylene oxide (PEO)/nano-hydroxyapatite scaffold in mature rats. Chitosan and PEO solution with the weight ratio of 80:20 and 70:30 were prepared, and 2% weight of nano-hydroxyapatite was added. Nanofibers were prepared using the electrospinning method, and the morphology was studied using scanning electron microscopy (SEM). Afterwards, the BMSCs of mature rats were cultured on nanofibers and differentiated by adding a differentiation medium. The survival of the differentiated cells was evaluated at the end of the first, second, and third week using acridine orange staining, and the morphology of the differentiated cells exposed to nanofibers was assessed using SEM. The mean diameter of the nanofibers with the ratio of 80:20 was 150±17 nanometers. The differentiation of BMSCs into the osteoblast-like cells on nanofibers was confirmed using Alizarin red staining. The results indicated a significant decrease in the survival of the differentiated cells in the nanofiber groups by the end of the third week of differentiation compared to the control samples. According to the results, BMSCs could be differentiated into osteoblast-like cells in the presence of the chitosan/PEO nanofibers containing nano-hydroxyapatite.

The antimicrobial activity of a wound dressing is a key factor for preventing and treating wound infection. The current study evaluated the physiochemical properties and antimicrobial activities of semi-IPNs (interpenetrating polymer networks) based on chitosan/polyvinyl alcohol (PVA) films and nanofibers as candidates for wound dressings and investigated the effects of morphologies (nanofibrous mats and films), crosslinking conditions of chitosan chains (uncrosslinked and crosslinked with genipin), and the presence of antibacterial drug (doxycycline) on their physicochemical and antibacterial properties. The morphology, chemical structure, fluid uptake, water vapor transmission rate, antimicrobial activity, and doxycycline release profile were assayed using SEM, FTIR spectroscopy, swelling test, permeation test, agar diffusion antibiogram, and dissolution test, respectively. The results demonstrated that crosslinking chitosan with genipin reduced the diameter of nanofibers, fluid uptake, and drug release from both nanofiber mats and film samples. According to the results, wound dressings with film morphology have better antimicrobial activity than those with nanofiber. The chitosan/PVA/Doxycycline 1% film has the potential for use as an antimicrobial wound dressing.

Optimal and appropriate antibiotic prescription for preoperative prophylaxis is an essential issue in hospitals. The nobility of the present study was to determine the rate of optimal antibiotic usage for preoperative prophy-laxis in Shahid Beheshti University hospitals in 2014.

In this observational cross -sectional study, 200 phy-sicians employed in Shahid Beheshti University hospitals who performed sur-gical procedures were enrolled in the study and the rate of optimal antibiotic utilization for preoperative prophylaxis was evaluated.

It was obtained that 64% of physicians had appropriate attitude and 41% had sufficient practice. The concordance rate according to the guidelines was medium in 52%, high in 29%, and low in 19%

It was ultimately attained that optimal antibiotic for preoperative prophylaxis is used by nearly half of physicians and also two third have appro-priate perspective regarding the antibiotic usage.

Umbelliprenin is a sesquiterpene coumarin with vitro anti-carcinogenic activities. The aim of this study was to investigate the antitumor effects of umbelliprenin in animal models of colorectal cancer. The cytotoxic effects of umbelliprenin were explored on CT26 and L929by MTT assay. In this study, colorectal tumors developed in mice by intradermal injection of CT26 cell line. Tumor size, serum levels of IFN-γ and IL-4 by ELISA, and Ki-67, MMP2, MMP9, VEGF and E-cadherin markers by IHC method were evaluated. The results showed that umbelliprenin inhibited the cancer cells in a concentration-dependent manner. IC50 Evaluation showed that L929 cells were more resistant to Umbelliprenin than CT26 cells. Umbelliprenin treatment in both tumor-bearing mice and control normal mice showed significantly increased IFN-γ and decreased IL-4(P

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Although the etiology of PD is unknown, but major biochemical processes such as oxidative stress is largely described. Angiotensin II activates NADPH depending oxidases and produce superoxides formation. Morus nigra L. extract is an Angiotensin Converting Enzyme (ACE) inhibitor and tested for anti-Parkinsonism effects by biochemical and behavioral evaluations.
In total 48 Male Wistar rats weighting 200-250 g were divided into 4 groups: (1) Sham (normal saline was injected in the left SNC), (2) Neurotoxin (injection of 6-hydroxydopamine into left SNC), (3) Morus nigra L. aqueous extract and (4) captopril. Morus nigra (10 mg/kg) and captopril (5 mg/kg) were daily-injected i.p. from 6 days before neurotoxin injection, until one day after 6-hydroxydopamine injection. Muscle stiffness and apomorphine test were assessed in 6 rats of any groups after two weeks. Protein oxidation, lipid peroxidation and ACE activity were assessed in brains of 6 rats of each group after 24 hours.
Rotation test with apomorphine, Rigidity with Murprogo’s test, and lipid peroxidation in sham, captopril and Morus nigra groups were significantly lower than neurotoxin group. Protein oxidation in Morus nigra group was significantly lower than neurotoxin group. Brain ACE activity in neurotoxin, captopril and Morus nigra groups were inhibited.
Morus nigra L. extract had protective effects on neuronal oxidation and death and improved signs of PD possibly by ACE inhibition.

Glioblastoma multiforme, the most common, aggressive malignant brain tumor which affects patients of all ages, is principally resistant to treatment. Ciprofloxacin is an antibiotic that belongs to the fluoroquinolones. There are welldocumented observations which indicate that ciprofloxacin has substantial anti-proliferative, apoptotic, cytotoxic and oxidative stress activities on various tumor cell lines.
We exposed the glioblastoma A-172 cell line to ciprofloxacin for 24, 48 and 72 h. Cytotoxicity was measured using MTT assay. The levels of Bax as an apoptotic and Bcl-2 as an anti-apoptotic protein were measured by ELISA and oxidative stress by the malondialdehyde assay.
Ciprofloxacin induced tumor cell death in a dose-dependent manner with an IC50 value of 259.3 μM at 72 h. We observed an increase in Bax levels, a decrease in Bcl-2 concentrations and increased Bax/Bcl-2 ratio under the influence of ciprofloxacin. Malondialdehyde levels, as an important marker of oxidative stress, increased in the human glioblastoma A-172 cell line.
These results indicated that ciprofloxacin had anti-tumor, cytotoxic and apoptotic effects in the human glioblastoma A-172 cell line which might be useful as an adjuvant added to a glioblastoma multiforme chemotherapeutic protocol in the future.