nematollah gheibi

Influenza and coronavirus pneumonia have caused a significant healthcare burden globally, raising growing concerns. The crisis and burden on public health have prompted an urgent need to find and develop medications to reduce the destructive effects of these diseases. Recently, there has been intense interest in evaluating the potential benefits of herbal drugs for managing viral infections. Due to their antioxidant, anti-mutagenic, anti-inflammatory, and anti-cancer effects, flavonoids appear to be promising agents for treating patients infected with viruses. In the field of natural medicine, the inhibitory role of flavonoids in the fusion and entry of different viruses may offer a hopeful contribution against influenza and coronavirus. Therefore, in this review, we discuss the pathogenesis of influenza and coronavirus and the role of flavonoids during infection, focusing on how they prevent the attachment and entry of viruses into host cells. In this regard, we have summarized the most recent related literature to provide valuable information about the effects of flavonoids on virus-host fusion, virus entry, and other related downstream mechanisms. We hope that these natural compounds will be suitable and safe adjuncts to other therapeutic drugs and approaches.

Coronavirus disease 2019 (COVID-19) is a human viral infectious disease caused by a coronavirus, known for its high transmission rate. As there is no specific drug for COVID-19 treatment, therapy is primarily symptomatic. Ivermectin, an FDA-approved antiparasitic agent, has recently shown antiviral activity against a broad range of viruses.

Previous studies have indicated that ivermectin, as an inhibitor of inflammation, could be useful in treating COVID-19.

In this study, we evaluated the structural characteristics of ivermectin-(NF-κB/MAPK10/MAPK14) complexes using molecular docking and molecular dynamics (MD) simulation methods. The docking process was performed to determine the best conformation of the complexes. Complexes with the best binding energies were selected as models for the MD simulation process. Furthermore, the structural (RMSD, H-bond) properties and interactions of the complexes were evaluated. Additionally, to calculate the binding free energy, PMF and MMPBSA calculations were carried out.

The molecular docking results showed that the binding energy of the ivermectin-NF-κB complex was higher than that of the other two complexes. Moreover, the MD simulation results for the ivermectin-NF-κB complex demonstrated that the complex equilibrated after 10 ns, and the number of H-bonds increased during the simulation. The binding energy of the ivermectin-NF-κB complex was calculated as 3.3 kcal/mol.

Ivermectin binds to NF-κB with high affinity, suggesting that this protein can be an appropriate drug target to decrease inflammation, confirming the anti-inflammatory activity of ivermectin. Thus, ivermectin could be a good candidate for treating SARS-COV2 infections.

 Addressing the Coronavirus disease 2019 (COVID-19) pandemic remains a significant challenge for healthcare systems globally. Despite the absence of a proven cure, ivermectin has been proposed as a potentially effective agent against it.

 This study aimed to evaluate the therapeutic effects of ivermectin compared to a placebo group in non-critically ill confirmed COVID-19 patients.

 A double-blind, randomized clinical trial was conducted on 110 patients with moderate-to-severe (non-critical) confirmed COVID-19 infection. The patients were equally divided into two groups, with one group receiving ivermectin tablets (14 mg every 12 hours for three days) and the other group receiving a placebo. The efficacy and safety of ivermectin were assessed in both groups.

 A total of 110 patients, including 62 (56.4%) men and 48 (43.6%) women, with an average age of 53.36 ± 15.10 years, were enrolled in our double-blind, randomized clinical trial. The baseline characteristics of the two groups were similar. The findings demonstrated that ivermectin significantly reduced the need for Intensive Care Unit admission (32.7% vs. 5.5%; P < 0.001), hospitalization duration (six vs. four days; P < 0.001), and median time to symptom resolution period (P < 0.05) in COVID-19 patients compared to the placebo group, without any serious side effects (P > 0.05).

 Ivermectin appears to be a potentially effective and safe medication for COVID-19 patients with moderate disease.

Human interferon gamma (hIFN-γ) as a pleiotropic cytokine, modulates both innate and adaptive immune networks and is important to the function of virtually most immune cells such as macrophages and T lymphocytes. It was originally discovered, and named, as a secretory factor that interferes with viral replication. The hIFN-γ has a multitude of roles in immune modulation and broad-spectrum pathogen defense including fungal, bacterial, and viral infections. In 1986, early clinical trials of IFN-γ initiated to evaluate its therapeutic potential. The initial studies focused on the tolerability and pharmacology of IFN-γ and systematically determined its antitumor and anti-infection activities. Nowadays, it has been approved for treatment of chronic granulomatous disease and malignant osteopetrosis, and its application as an immunotherapeutic agent against cancer and inherited and autoimmune disorders is an increasing prospect. The hIFN-γ has been heterologously expressed in different expression systems including prokaryotic, protozoan, fungal (yeasts), plant, insect and mammalian cells. However, these expression systems did not reveal satisfactory results in terms of yield, the biological activity of the recombinant protein or economic viability. Thus, it is essential to find an efficient expression system to produce glycosylated recombinant hIFN-γ with correct folding, biologically active and a high half-life in the bloodstream. The review aims to gather available information from previous studies on the production of hIFN-γ and provides direction to future researches in this field

Human bone marrow mesenchymal stem cells (hBM -MSCs), as supporters for hematopoiesis, differentiate into osteoblasts and adipocytes. Studies showed that infection of hBM -MSCs by Parvovirus B19 (B19V) can affect the differentiation capability of hBM -MSCs. This study aims to evaluate B19V effects on the differentiation of hBM -MSCs.

In this experimental study hBM -MSCs were cultured up to passage 3. Nucleofection was subsequently employed to deliver a plasmid containing the B19V genome into the cells. The transfected cells were then differentiated into osteoblast and adipocyte lineages. qRT -PCR was then performed to analyze the differentiation 14 days after transfection.

On the 14th day after induction the findings demonstrated a significant increase in adipocyte -specific (PPARγ and LPL) gene expression compared to the control group (p<0.05) and a slight but not statistically significant decrease in the expression of the osteocyte -specific genes (RUNX2 and osteocalcin) (p>0.05).

The results suggest that B19V infection can promote the differentiation of hBM -MSCs towards adipocytes and affect the bone marrow microenvironment as well as hematopoiesis.

Breast cancer (BC) is the most common malignancy in women worldwide. The methylation status of MyoD1, a tumor suppressor gene, is enrolled in various cancers, i.e., BC. Various studies showed the impact of MyoD1 epigenetic dysregulation in BC. This study aimed to investigate the methylation status and expression level of MyoD1 in BC patients and its association with the expression of DNMT1.

This case-control study was conducted on 30 cases (pathology-confirmed ductal carcinoma) and 18 controls (fibroadenoma and fibrocystic masses), referred to Velayat Hospital, Qazvin, Iran. The expression of the MyoD1 and DNMT1 and the promoter methylation of the MyoD1 were evaluated in tissue blocks of BC patient masses using qRT-PCR and MS-PCR assays, respectively. SPSS 24.0 was used to analyze the data.

The MyoD1 promoter is hypermethylated in BC patients compared to controls (p =0.001). The expression level of MyoD1 in BC patients was significantly reduced compared to controls (fold change =0.13, p =0.042). In addition, in BC patients, the reduced expression level of MyoD1 was significantly associated with methylation of the MyoD1 promoter (p =0.001). There is no significant difference between the expression level of DNMT1 in BC patients and controls (p =0.197). A significant association is found between the expression of DNMT1 and the methylation status of the MyoD1 promoter (p =0.038).

The expression level of MyoD1 is affected by the methylation status of the promoter of this gene. Moreover, the expression level and methylation status of MyoD1 are correlated with clinical parameters.

Low-risk and efficient therapeutic approaches have been central themes of many recent studies on melanoma treatment. Accordingly, here the aim was to study the impact of nicotinic and picolinic acid-omega 3 complexes on mushroom tyrosinase and their antiproliferation effect on the A-375 melanoma cell line. The cells were exposed to various levels of nicotinic-omega 3 and picolinic-omega 3 complexes. To screen for cell proliferation, MTT assay and inverted microscope were applied. Kinetic analysis of the inhibitory effect of the complexes on tyrosinase enzyme was also evaluated. Nicotinic-omega 3 and picolinic-omega 3 complexes significantly reduced cell growth with a concentration and time-dependent behavior. The significant inhibitory effect for picolinic-omega-3 was observed in a lower concentration as the time increased. However, nicotinic-omega 3 did not manifest a similar potency level as in 24 h only 200 μM was significant, and in 48 h and 72 h, the significance in inhabitation was observed between 150-200 μM. Meaning that the growth and multiplication of the cells under those treatments decreased considerably. These two complexes affected mushroom tyrosinase in a competitive inhibitory manner with Ki values of 5.2 and 5.1 mM for nicotinic - omega-3 and picolinic - omega-3, respectively. It seems nicotinic -omega 3 and picolinic – omega 3 complexes are capable of solid antiproliferative potential against melanoma cells, indicating their potential applicability for the melanoma cancer treatment.

 Urinary tract infections (UTIs) that influence millions of humans yearly are still among the most common infections in the community and hospitals. This study aimed to investigate the prevalence of UTIs and their antibiotic resistance susceptibility in patients in Qazvin province, northwest Iran, from 2017 to 2019.

 This study was conducted on 3521 urine samples of patients referred to a non-hospital medical laboratory (Mehr) between April 2017 and January 2019. Samples were collected and processed immediately for laboratory analysis. Biochemical tests were conducted the bacteria identification, and the antibiotic susceptibility test of the bacterial isolates was determined using Kirby-Bauer disc diffusion.

347 of the 3521 urine samples had significant bacteriuria, with a prevalence of 9.9 %. Escherichia coli occurred more frequently (54.4 %), while Pseudomonas aeruginosa had the lowest frequency of occurrence (1.4 %) in the samples. Nitrofurantoin and Amikacin were the most effective antibiotics against gram-negative and positive, respectively. This study revealed that bacterial resistance in UTIs continues to be a great problem and needs drug resistance surveillance periodically.

Malignant melanoma is an aggressive skin cancer whose survival rate is extremely low. Commencing apoptosis is believed to be a significant issue in cancer treatment and targeting the apoptosis and WNT signaling pathways, which is probably a potentially successful strategy to overcome tumor plasticity in melanoma. We conducted the present in vitro study to investigate antiproliferative and apoptotic effects of Nic-ALA, as a new compound, on A375 melanoma cell line using MTT assay and flow cytometry, respectively. The gene expression profiles of the cancer cells were obtained for Bcl-2 and BAX as the main genes of the apoptosis signaling pathway and WIF1 and beta-catenin genes from the WNT signaling pathway with qRT-PCR. Nic-ALA’s cytotoxicity on A375 melanoma cell line from MTT assay was obtained with IC50 166.7, 144.2, and 146.1μM. This novel derivative induced 11.3, 46.1, and 85.7% of apoptosis in 24, 48, and 72h time points, respectively. In the treated cells, the expression of BAX, beta-catenin, and WIF1 genes increased, while the expression of Bcl-2 decreased significantly at 200μM concentration and the treated times of 48 and 72h. The antiproliferation of Nic-ALA at a lower value than what we found in nicotinic acid alone represented the higher bioavailability and transport efficiency of this novel derivative through A375 melanoma cell line. Its antipoetic effects were obtained by increasing the apoptosis rate and expression of the Bax gene and reducing Bcl-2 gene expression. Upregulation of WIF1 and beta-catenin in the WNT signaling pathway emphasized Nic-ALA’s anticancer effect on A375 melanoma cell line.

Betatrophin/angiopoietin-like protein (ANGPTL8) is defined as an adipokine that regulates blood glucose and triglyceride levels.

This study aimed to evaluate the effect of propolis supplementation for the first time on serum levels of the hormone betatrophin, as a drug target in the treatment of dyslipidemia, in male endurance athletes for four weeks.

44 male athletes with an average age of 22 ± 3 years, a height of 177.5 ± 6.5 cm, and a weight of 76 ± 6 kg were selected in Qazvin. They were randomly divided into four groups: Supplementation, placebo, physical activity, and control. The supplementation and placebo groups received two 500 mg tablets of propolis and cellulose (in terms of shape and color, are similar to the original supplement and have no properties, flavor, and aroma) once after lunch and once after dinner, respectively. The drug treatment lasted for four weeks. The athletes' weight and serum levels of betatrophin were measured at the beginning and the end of 4 weeks of treatment. The ELISA method was used to assess the serum concentration of betatrophin. Analyzes were performed by the ANCOVA method.

The results showed that the long-term endurance training plus propolis supplementation would result in significant changes in the betatrophin serum levels and weight in participants (P = 0.001), but in the athletes without supplementation, these changes were not significant (P > 0.05).

The results indicated that betatrophin serum levels in endurance athletes are increased by propolis supplementation, and their weight is decreased.

The acute respiratory syndrome named “COVID-19” is caused by a novel coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). Lack of specific antiviral drugs or proper vaccination has led to the development of new therapeutic methods against this virus.
Objective The Mpro 3Clpro is the main protease of the SARS-CoV-2 which plays an important role in replication and transcription of the virus. Therefore, targeting this enzyme is a valuable approach for drug development.

In the present study, the structural properties of 69 anti-migraine and 212 anti-HIV drugs were first obtained from Drug Bank database. To select the appropriate drugs for the enzyme inhibition, the AutoDock Vina software was used. The molecular dynamics (MD) simulation method was applied for better recognition of the structural changes.

We identified Rimegepant (PubChem ID: 51049968), Dihydroergotamine (PubChem ID: 10531) and Ergotamine (PubChem ID: 8223) as potential inhibitors of Mpro 3Clpro. These complexes were equilibrated after 70 ns.

Among these compounds, the anti-migraine drug “Rimegepant” showed the highest affinity for binding to the Mpro 3Clpro (-60.8 kJ/mol). This study provides enough evidence for further accomplishment of the identified compounds in the development of effective therapeutics methods against COVID-19.

Due to imprecise/missing data used for parameterization of ordinary differential equations (ODEs), model parameters are uncertain. Uncertainty of parameters has hindered the application of ODEs that require accurate parameters.

We extended an available ODE model of tumor‑immune system interactions via fuzzy logic to illustrate the fuzzification procedure of an ODE model. The fuzzy ODE (FODE) model assigns a fuzzy number to the parameters, to capture parametric uncertainty. We used the FODE model to predict tumor and immune cell dynamics and to assess the efficacy of 5‑fluorouracil (5‑FU) chemotherapy.

FODE model investigates how parametric uncertainty affects the uncertainty band of cell dynamics in the presence and absence of 5‑FU treatment. In silico experiments revealed that the frequent 5‑FU injection created a beneficial tumor microenvironment that exerted detrimental effects on tumor cells by enhancing the infiltration of CD8+ T cells, and natural killer cells, and decreasing that of myeloid‑derived suppressor cells. The global sensitivity analysis was proved model robustness against random perturbation to parameters.

ODE models with fuzzy uncertain kinetic parameters cope with insufficient/imprecise experimental data in the field of mathematical oncology and can predict cell dynamics uncertainty band.

Oxidative stress is a leading factor in developing silver nanoparticle-induced toxicity. 

This study evaluated the effects of oral prescription of different doses of silver nanoparticles and propolis on lipid peroxidation in male Wistar rats.

The male Wistar rats were randomly divided into four groups. Control group and three different treatment groups with oral prescription of 30 ppm, 60 ppm, and 60 ppm of silver nanoparticles with 200 mg/kg of propolis. The serum level of Malondialdehyde (MDA) was measured by Thiobarbituric Acid Reactive Substances (TBARS) assay using Thiobarbituric Acid (TBA). 

 The serum level of MDA as a marker of lipid peroxidation in the control group was 1.92 mM/mL, and in other groups that received silver nanoparticles (30 ppm, 60 ppm, 60 ppm with 200 mg/kg propolis) were respectively 2.82, 3.83 and 2.62 mM/mL. MDA level also increased at the doses of 30 ppm and 60 ppm compared to the control group and decreased when propolis was prescribed with silver nanoparticles in the third group; however, its value did not reach the level of the control group. Minimal levels of serum lipid peroxidation were observed when silver and propolis nanoparticles were administered to male rats.

The mixture of silver nanoparticles and propolis reduces the toxic effects of silver nanoparticles; it preserves and increases the efficiency of this compound in medical applications.

Humic acid (HA) and Fulvic acid (FA) are major members of humic substances, which are extracted from organic sources including soil and peat. The pro-apoptotic and anti-melanogenic effects of HA and FA at the cellular and molecular levels in the A375 human melanoma cell line were examined in this study.  The cytotoxicity effect of HA and FA were evaluated by cell viability assay. Apoptosis and cell cycle were investigated by flow cytometry. Real-time PCR was carried out to measure the expression of BAX, BCL-2, and Tyr genes. Moreover, the changes in nanomechanical properties were determined through atomic force microscopy (AFM).  It was found that HA and FA decrease cell viability with an IC50 value of 50 µg/ml (dose-dependent) for 14 hr, arrested cells in the G0/G1 phase, and increased the sub-G1 phase (induce apoptosis). Based on the AFM analysis, Young’s modulus and adhesion force values were increased, also ultrastructural characteristics of cells were changed. Results of Real-time PCR revealed that HA and FA lead to a decrease in the expressions of BCL-2 and Tyr genes, and increase the BAX gene expression. These results exhibited that HA and FA possess pro-apoptotic effects through increasing the BAX/ BCL-2 expression in A375 cells. These molecular reports were confirmed by cellular nanomechanical assessments using AFM and flow cytometry. In addition, HA and FA inhibited melanogenesis by decreasing the expression of the Tyr gene. It is worthwhile to note that, HA and FA can be regarded to design new anti-cancer and anti-melanogenesis products.

Aerobic and intense exercises with an increase in free radicals cause damages at the cellular level, heart disease, cancer, and the development of aging processes, which one of its symptoms is increased serum concentrations of liver enzymes. 

The purpose of this study was to investigate the concurrent effect of four weeks of aerobic training and propolis supplementation on the activity of liver enzymes, including ALT, AST, and SOD in endurance athletes.

Thirty-two male athletes (age: 21±1.4 years) in track and field were randomly divided into three groups: exercise group, exercise with placebo group, and exercise with supplement group. Propolis supplementation was taken as two tablets (500 mg) twice a day and aerobic exercise was performed for 4 weeks and in 24 sessions with an intensity of 60 to 65% of heart rate. The statistical method was done using one-way ANOVA and Tukey post hoc test by SPSS v. 18 software.

The results showed that there was a statistically significant difference between groups in serum levels of SOD, AST, and ALT (P<0.05). There was not a statistically significant difference between the exercise group and placebo+exercise group in serum levels of SOD, AST, and ALT (P>0.05).

The results showed that aerobic exercise alone can increase SOD levels and propolis supplementation with aerobic exercise can reduce AST and ALT serum levels and lead to improved liver cell function.

Breast cancer is the most common type of cancer among women worldwide. Traditional treatments, including chemotherapy, surgery, mastectomy, and radiotherapy, are commonly used. Because of the limitation of the aforementioned methods, novel treatment strategies are needed. Methotrexate is a chemotherapeutic drug, which is commonly used to treat breast cancer. Because of the side effects of the free drug, the liposomal form of the drug is suggested.

Liposomal methotrexate was prepared and the encapsulation efficiency was measured. Moreover, the particle size and the zeta potential were measured. The liposome morphology was confirmed using transmission electron microscopy. The MTT assay was done to examine the cytotoxicity of free and encapsulated methotrexate on BT-474 cell line. The Annexin-V/PI dual staining assay was performed to assess the apoptosis in BT-474 breast cancer cells via the flow cytometry method.

The transmission electron microscopy results confirmed the integrated and spherical structure of the nanoparticles. The results of drug release showed that in acidic pH (5.4), more than 90% of the drug was released after 24 hours, which was higher than 2 other pHs. Furthermore, the IC50 value of liposomal methotrexate was determined as 2.15 and 0.82 mg/mL for 24 and 48 hours. The flow cytometry results confirmed that liposomal methotrexate had a greater cytotoxic effect on cancer cells compared with free methotrexate.

Because of the advantages of liposomal based nanocarriers, in this study, liposomal methotrexate could be suggested as an appropriate candidate to treat breast cancer.

New complexes of quercetin esterification with alpha linolenic acid (ALA) and linoleic acid (LA) were applied as inhibitor of tyrosinase as the main melanogenesis.enzyme The most abundant flavonoid compound, quercetin was considered as the base of esterification with poly unsaturated fatty acids (PUFA). The new derivatives including quercetin- ALA (complex I) and quercetin- LA (complex II) were designed and their impacts on mushroom tyrosinase (MT) were assessed by experimental and theoretical studies. The new complexes I and II were induced competitive inhibition on tyrosinase enzyme with Ki of 0.59 and 0.40 mM, respectively. The molecular analysis of docking revealed that the complex II has a better ability to interact with enzyme than the complex I and the nature of interactions was obeyed from hydrophobic manner. So, the esterification of quercetin by above mentioned fatty acids achieved strength inhibitors against tyrosinase and because of their abundant in natural sources and importance in lifestyle, it is proposed to utilize them in medicine, cosmetics, agriculture and food industries. Their other biological properties need more investigations.

According to cancer’s global statistics, there will be 27.5 million new cases of cancer each year by 2040, therefore, it is crucial to achieve a deeper understanding of the cancer progression mechanisems and immune system functions in response to it. Nowadays, Computational models are widely used to capture dynamics of the tumor-immune system (TIS). The proposed model on this manuscript is on the basis of the ordinary differential equations which mechanistically models the interactions of tumor cells, CTLs, NKs and MDSCs. CTLs and NK cells are the most important cells of adaptive and innate immune system, respectively that encounter with tumor cells, while MDSCs as immature immune cells suppress the immune responses in the inflammatory environments. Due to the error of the in vivo/in vitro experiments, vagueness, imprecise information, incomplete data and natural variability of the tumor-immune system emerges between different individuals, the kinetic parameters of computational models are uncertain that this uncertainty can be captured by fuzzy sets. Hence, we assign fuzzy numbers with triangular membership functions instead of crisp numbers to some kinetic parameters of the tumor–immune system model. In fact, the uncertainty in the kinetic parameters of the ordinary differential equations affects the dynamic of the system species. In this essay, for the first time, a fuzzy number has been used to model the uncertainty of the parameters of the ODE model. Our data reveals that increasing/decreasing the uncertainty region of the model's fuzzy parameters increases/decreases the uncertainty region of dynamics of species. Furtheremore, the simulations of the model in the crisp setting of parameters show that the repition of 5-FU treatment for inhibition of MDSCs dramatically inhibits tumor cells and eradicate tumor.

 Viral hepatitis B is a substantial contributor of dreadful liver disease and hepatocellular carcinoma (HCC) and imposes ponderous burden on the ministry of health around the world. There are no adequate data on the prevalence of Hepatitis-B surface antigen (HBsAg) among Afghan refugees, especially in one of their favorable host countries, Iran. This seroprevalence study aimed to estimate the prevalence rate of HBsAg among Afghan refugees to schedule much more efficient preventive measures.

In the current cross-sectional study, data were gathered for a total of 488 Afghan refugees referred to Mehr Medical Diagnostic Laboratory from April 2014 to January 2018. Initial information including age, sex, and education status were extracted. Collected samples from the patients were conducted using the General Biological Corporation (GBC) ELISA Kit to detect seronegative or seropositive HBsAg cases. Following all data were analyzed by SPSS version 16 software.

Sixteen cases with positive HBsAg were detected in 488 Afghan patients referred to the Mehr Laboratory from April 2014 to January 2018. The overall prevalence of HBsAg was calculated 3.3% (2.3% in females and 1% in males). The highest frequencies of HBsAg were associated to the age group of 21 to 30 years with 1.2% and none education level group with 1.8%.

According to the outcome of current study, free vaccination, treatment and screening seropositive individuals in borders will be applied to assist the design and management of preparatory preventive strategies.

Coronavirus Disease 2019 (COVID-19) is a viral pneumonia emerged in December 2019 in Wuhan, China. Its cause is a new virus from the coronavirus family scientifically named Coronavirus Acute Respiratory Syndrome 2 (SARS-CoV-2). In this review study, articles published in English until March 23, 2020 on new coronavirus infection were reviewed. These articles are obtained by searching in PubMed, Scopus and Google scholar databases using keywords "SARS-CoV-2", "COVID-19" and "Coronavirus". The latest COVID-19 statistics and information were extracted from the websites of World Health Organization and the Centers for Disease Control and Prevention. we investigated the effect of different compounds on the key macromolecules in promoting SARS-COV-2 infection using computational methods and bioinformatics analysis that can be considered as the best targets for designing inhibitory drugs. The most important macromolecules were Angiotensin Converting Enzyme 2 (ACE2) and Transmembrane Protease Serine 2 (TMPRSS2) receptors of the host cell surface and the structural and non-structural proteins of the virus. The most important structural protein was Spike, playing an important role in binding the virus to the ACE2 receptor of the host cell and the entery of the virus genome into it, while the key non-structural proteins were 3-Chymotrypsin-like protease (3CLpro), RNA-dependent RNA polymerase (RdRp), Papain-like cysteine proteinase (PLpro), and non-structural protein 13 (nsp13) helicase which are involved in viral genome replication and the virus’ release from the host cell.

 Ionizing and non-ionizing radiation are widely used in the diagnosis and treatment of diseases. Considering the potential risks of radiation, radiation safety training courses are important for medical staff.

 The aim of this study was to investigate the effectiveness of one-day radiation safety training program in increasing the radiation safety knowledge of physicians.

 In this descriptive-analytical study, subjects were 12 physicians (6 general practitioners and 6 non-radiologist specialists) participated in the training program organized by Qazvin University of Medical Sciences in 2018. A researcher-made questionnaire was used for surveying physicians before and after the training. The mean and standard deviation of the scores were first calculated. Then, the pre- and post-test scores were compared using Wilcoxon signed-rank test, and the correlation of these scores with their age, gender, expertise area, and work experience was examined by Spearmanchr('39')s correlation test.

 The mean total scores of the physicians before and after training were 7.00±2.56 (ranged 3-11) and 11.92± 2.31 (ranged 8-15) out of 18, respectively. The radiation safety knowledge of physicians significantly increased after training (P<0.001). No significant relationship was found between their scores and their age, gender, expertise area and work experience.

 The radiation safety training program was effective in increasing the radiation safety knowledge of physicians and it can be used for a larger community of physicians.

Hepatocellular carcinoma (HCC) is one of the leading fatal neoplasms and the most common primary liver malignancy worldwide. Peptide hormone ANGPTL8 (betatrophin) may act as an important regulator in HCC development through the Wnt/β-catenin pathway. We aimed to evaluate the effects of recombinant ANGPTL8 on Wnt/β-catenin signaling in human liver carcinoma cells (HepG2) and their viability. The expression of ANGPTL8 was conducted in the pET-21b-E. coli Bl21 (DE3) system and the produced peptide was purified. HepG2 cells were treated with different concentrations of ANGPTL8 (25, 50, 100, 150, 200, and 250 ng/ml) for 24, 48, and 72 hr. MTT assay was performed to detect the viability of treated cells, and apoptotic induction by ANGPTL8 was measured by flow cytometry assay. Finally, using qRT-PCR the mRNA levels of Wnt signaling modulators WIF-1 and β-catenin were evaluated in treated cells. MTT assay showed that ANGPTL8 inhibits proliferation of HepG2 cells moderately in a time-independent manner. The highest concentration of the ANGPTL8, 250 ng/ml, reduced cell proliferation after 24, 48, and 72 hr similarly about 30%. In the same concentration of ANGPTL8, after 24 hr of treatment flow cytometry assay revealed a mild increase in early and late apoptosis up to 7.7 and 14.3%, respectively. The qRT-PCR showed that in a concentration-dependent and time-independent fashion, the expression of WIF-1 and β-catenin genes respectively increased and decreased significantly (P<0.05). Our findings suggest that ANGPTL8 may act as a moderate suppressor against HCC cell proliferation possibly via affecting Wnt signaling modulators.

Fibroblast growth factor receptor 2b (FGFR2b) plays a crucial role in cell signaling pathway, regulating several key biological processes, including cellular differentiation and proliferation. Different types of cancers, including breast cancer, have also been associated with various genetic alterations in the kinase domain of FGFR2b. The present study was conducted to shed new light on a possible mechanism, by which flavonoids alter FGF cell signaling. Recombinant pLEICS-01 expression vectors containing the gene encoding the FGFR2b kinase domain were transformed to E. coli BL21 (DE3). Expression of the recombinant protein was then induced with IPTG. Next, the protein was purified by affinity chromatography. The recombinant protein functionality was assessed using PAGE, by analyzing interactions of the protein with the wild type and the mutant SH2 domains of phospholipase C-γ (PLC-γ). Finally, stability and structural changes of the kinase domain were studied upon interaction with gallic acid, naringenin, quercetin and catechin. The PAGE analysis clearly demonstrated that the recombinant protein interacts only with the wild type SH2 domains of PLC-γ, suggesting the kinase domain is functional. The results also showed that presence of the flavonoids cause a red-shift in the intrinsic fluorescence emission spectra of the kinase domain, suggesting a change in the overall structure of the kinase domain. Further structural studies, using a comprehensive step chemical denaturation analysis, conspicuously showed that the presence of the flavonoids significantly changed the tertiary structure of the kinase domain. The comprehensive structural analyses revealed that the flavonoids significantly impinge on the tertiary structure of the kinase domain thereby suppressing fibroblast growth factor signaling.

L7/L12 is a protective antigen conserved in main Brucella pathogens and is considered as potential vaccine candidate. Outer membrane protein 2b is an immunogen conserved in all Brucella pathogens.

The purpose of the current study was to in silico design a L7/L12‑SOmp2b fusion protein and in vitro production of the chimera. Two possible fusion forms, L7/L12‑SOmp2b and SOmp2b‑L7/L12, were subjected to in silico modeling and analysis. Cloning and expression of the fusion protein has been done in the pET28a vector and Escherichia coli Bl21 (DE3), respectively.

Analysis and validation of the fusion proteins three‑dimensional models showed that both models are in the range of native proteins. However, L7/L12‑SOmp2b structure was more valid than the SOmp2b‑L7/L12 model and subjected to in vitro production. The major histocompatibility complex II (MHC‑II) epitope mapping using Immune Epitope DataBase indicated that the model contained good MHC‑II binders. The L7/L12‑Omp2b coding sequence was cloned in pET28a vector. The fusion was successfully expressed in E. coli BL21 by induction with isopropyl‑β‑d‑thiogalactopyranoside. The rL7/L12‑SOmp2b was purified with Ni‑NTA column. The yield of the purified rL7/L12‑SOmp2b was estimated by Bradford method to be 240 µg/ml of the culture. Western blot analysis revealed a specific reactivity with purified rL7/L12‑SOmp2b produced in E. coli cells and showed the expression in the prokaryotic system.

Our data indicates that L7/L12‑SOmp2b fusion protein has a potential to induce both B‑ and T‑cell‑mediated immune responses and it can be evaluated as a new subunit vaccine candidate against brucellosis.

Only natural materials were used for healing the wounds. As wax honey, ostrich oil and propolis have anti-inflammatory and anti-bacterial effects, this study was launched to investigate their efficacy in skin wound healing.
In this experimental study, 40 Vistar male rats were divided into 5 groups which included a control group, honey wax group, honey wax and propolis group, honey wax and ostrich oil group, and honey wax and bee wax group. In all 5 groups, wound-surface measuring continued until the 10th day and hydroxyproline of the urine was analyzed on Day 10; and the data were analyzed using SPSS software.
The percentage of recovery was different on the sixth, eighth and tenth days of treatment among all the treated groups and the control group. An evaluation of the analyzed hydroxyproline in the urine also showed a significant difference in all treated groups on the one hand compared to the control group, on the other.
The results of the recovery and percentage and concentration of hydroxyproline in urine, showed the restoration properties of honey not only has a synergistic effect but also accelerates the wound-healing process when used along with ostrich oil and propolis.