elham safarzadeh

Systemic sclerosis (SSc) is a chronic autoimmune disorder characterized not only by fibrosis and vasculopathy but also by inflammation. Previous studies have demonstrated monocyte involvement in SSc development, suggesting a role for immune dysfunction in SSc pathogenesis. To investigate the relationship between SSc’s clinical manifestations and altered levels of monocyte subpopulations. Twenty-six patients meeting the ACR/EULAR SSc criteria along with twenty healthy individuals as the control group, were enrolled in the study. Peripheral blood mononuclear cells (PBMCs) were obtained from heparinized blood samples of both the SSc patients and the control group. Subpopulations of monocytes were assessed based on HLA-DR, CD14, and CD16 expression using multi-color flow cytometry. The one-way ANOVA, Student’s t-test, and Mann-Whitney U test were employed for normally and non-normally distributed data. The Spearman correlation test was utilized to identify correlations between the variables. The SSc patients showed a significant increase in the number of circulating peripheral blood monocytes (p<0.001). The percentage of CD16+ monocyte subpopulations was higher in the SSc cases compared to the control group. A significant decrease in the ratio of classic to non-classic monocytes was observed in SSc cases (7.43%) compared to the control group (52.09%, p<0.001). No association was observed between monocyte subpopulations and clinical characteristics of SSC. Our results showed an increase in the level of CD16+ monocytes in patients with SSc compared to healthy individuals. Further investigation is required to determine the clinical significance of this alteration.

The spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been undergoing variation. Most of the variants cause no concern for human health. Some others have had worse outcomes in terms of transmissibility, vaccination resistance, and, generally, the survival of patients infected with SARS-CoV-2.

This study investigated the mutation of interest in the receptor-binding domain (RBD) of SARS-CoV-2.

Ribonucleic acid (RNA) was extracted from 40 swap samples. Next, the polymerase chain reaction (PCR) assay was carried out to detect the RBD. Investigation of SARS-COV-2 RBD was performed completely by phylogenetic and tree alignment. The multiple sequence alignment (MSA) of the biological sequence of RBD was created by BioEdit, Snap Gene, and MEGA software and was then compared to sequences of different variants of SARS-COV-2 in the GenBank (National Center for Biotechnology Information). The Influenza Surveillance and Response System (GSAID) was used to detect mutations in the RBD sequence.

Multiple sequence alignment (MSA) RBD domain showed that the RBD domain sequence obtained from the Iranian patients’ highest identity by severe acute respiratory syndrome coronavirus 2 isolate MZ907347. Several mutations of interest, including A475V, L452R, V483A, and F490L, were detected in the RBD region. However, the dN/dS analysis detected positive selection in RBD regions.

Amino acid changes in the surface protein can significantly alter the viral function and/or interactions with neutralizing antibodies. Most of the nucleotide changes in the spike gene reduce infectivity. TheV503Wand P521Q mutations reduce infectivity, the A522Q mutation increases sensitivity to neutralizing antibodies, and the H519T mutation decreases susceptibility to convalescent sera.

Coccidiosis is the leading parasitic disease in poultry. One of the most critical Eimeria species, Eimeria tenella, lives inside the cecal epithelial cells and induces bloody coccidiosis. The present study evaluated the effect of radiation-attenuated E. tenella oocytes mixed with inulin adjuvant on broiler chicken. Initially, the effect of irradiation on oocyst attenuation was confirmed. Then, one-day-old broilers (n = 90) were divided into nine groups on seven days of age as follow: Group 1 (400 attenuated oocysts + 1.00 mg of adjuvant), group 2 (400 attenuated oocysts + 0.50 mg adjuvant), group 3 (200 attenuated oocysts + 1.00 mg of adjuvant), group 4 (200 attenuated oocysts + 0.50 mg adjuvant), group 5 (1.00 mg adjuvant), group 6 (400 attenuated oocysts), group 7 (commercial vaccine), group 8 (negative control) and group 9 (blank). On day 21, we performed a challenge with E. tenella oocytes and investigated oocyst output and average weekly weight throughout the study. At the end of the study, we evaluated macroscopic lesion, histology, cytokine level and leukogram status. The results showed a statistically significant difference among groups. Furthermore, the optimal dose was 400 irradiated oocysts and 1.00 mg of inulin. Moreover, an X-ray could reduce the virulence of E. tenella oocytes. Inulin alone or combined with attenuated oocysts showed an acceptable effect on evaluated parameters.

Coronavirus disease-2019 (COVID-19), an infectious disease, has been known as a worldwide pandemic involving many countries, including Iran. Meantime, the analyses of clinical and demographic features of the fourth surge in COVID-19 patients provide a better overview of disease management and mortality reduction.

This study aimed to identify the effective clinical and demographic hallmarks of the fourth wave of COVID-19 in Ardabil Province, Iran.

We carried out a population-based analytical cross-sectional study using clinical and demographic characteristics of COVID-19 from February 2021 to May 2021 among confirmed COVID-19 patients who were admitted to the hospital during the fourth surge. Predictors of intensive care unit (ICU) admission and death were evaluated by controlling for intervening variables.

We evaluated 500 patients, of whom 54.5% were men, and 45.5% were women. Among them, 35.1% of patients had hypertension as the main comorbidity, followed by diabetes (21.4%), cardiovascular disease (8.4 %), renal diseases (2.4%), and others. The findings indicated that increasing age has increased mortality among patients with COVID-19. Moreover, our results showed that among the analyzed items, age, sex, and cerebral vascular accident (CVA) were indicated as predictors of ICU admission.

This evaluation demonstrated that old age and comorbidities are two major risk factors for reducing the probability of recovery and increasing admission to the ICU. Therefore, elderly individuals with at least one co-morbidity are at higher risk of becoming infected.

Infection with COVID‑19 has resulted in considerable mortality all around the world. This study aimed to investigate the effect of convalescent plasma on the treatment of hospitalized patients with COVID‑19 in Imam Khomeini Hospital at Ardabil, Iran.

In this quasi‑experimental clinical trial, patients over 18 years of age with polymerase chain reaction‑positive COVID‑19 were admitted based on the clinical criteria of respiratory distress with hypoxia (O2 saturation <90) and tachypnea (R Relative Risk (RR) >24) with moderate‑to‑severe lung involvement and in the 1st week of respiratory disease who were not intubated were nonrandomly assigned to two groups: convalescent plasma therapy (CPT) group (197 cases) and control group (200 cases). We used the Chi‑square, t‑test, Fisher’s exact test, and Pearson’s correlation coefficient for statistical analysis.

Analyses revealed that length of stay in hospital was significantly lower in the CPT group as compared to the control group (P = 0.001). Twenty‑four cases (22.0%) in the CPT group and 85 cases (78.0%) in the control group needed intubation. Furthermore, mortality was 17 cases (18.3%) in the CPT group and 76 cases (81.7%) in the control group, the difference of which was also found to be statistically significant (P < 0.05).

It seems that CPT can be used as an alternative treatment at the early stages of COVID‑19 to prevent the progress of the disease, reduce the need for intubation and consequently the length of stay in hospital, and finally, decrease mortality

EZH2 (enhancer of zeste 2 polycomb repressive complex 2 subunit), as one of the polycyclic group proteins (PcGs), is an epigenetic regulator that plays a crucial role in the pathophysiology of hematologic malignancies through regulating cell differentiation. Also, it is well known that aberrant expression of specific transcription factors can be involved in the pathogenesis of various cancers. Herein, we aimed to suppress EZH2 expression in MOLT-4 cells, T-ALL (T cell acute lymphoblastic leukemia) cell line, and evaluate the role of EZH2 on the expression of transcription factors that regulate T cell maturation, differentiation, and apoptosis.

EZH2-siRNA was transfected into MOLT-4 cells, and the expression levels of EZH2, NOTCH1, TCF1, IKZF1, and NFATC1 were measured using real-time PCR. The MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay was performed to study the effect of EZH2 knockdown on MOLT-4 cell viability. The apoptosis rate of EZH2-siRNA transfected cells was assessed by flow cytometry. The interaction of mentioned genes was investigated using STRING and GO (gene ontology).

Our results have shown that EZH2-siRNA transfection can substantially decrease EZH2 expression in MOLT-4 cells. Besides, EZH2 suppression can upregulate NOTCH1, TCF1, IKZF1, and NFATC1 expression levels. EZH2 knockdown does not affect the viability and apoptosis of MOLT-4 cells. The most remarkable protein-protein interaction of EZH2 has been with NOTCH1. Besides, GO analysis has demonstrated that EZH2, NOTCH1, TCF1, IKZF1, and NFATC1 were located within nucleoplasm and can regulate RNA polymerase II-mediated transcription.

MOLT-4 cells harbor increased expression of EZH2 in comparison with normal human T cells. EZH2 knockdown can upregulate the expression of the transcription factors involved in T cell differentiation. Thus, EZH2 can halt the differentiation of immature lymphoblastic T cells.

Many studies have been performed about regenerative and immunomodulatory properties of mesenchymal stem cells (MSCs) and their application in different treatment approaches. The present study aimed to investigate the immunomodulatory effect of umbilical cord blood-derived mesenchymal stem cells (UCB-MSCs) on the gene expression profile of cytokines in stimulated T-lymphocytes. For this purpose, MSCs were isolated from umbilical cord blood samplesand cultured in Dulbecco's Modified Eagle Medium supplemented with 10% fetal bovine serum. The nature of MSCs was identified by flow cytometry analysis and differentiation to the adipocyte and osteocyte lineage. Moreover, to investigate the immunomodulatory effects of MSCs on T cells, a co-culture system was designed and expression levels of interleukin (IL)2, IL4, IL-6, IL-10, IL13, interferongamma (IFNγ), tumor necrosis factoralpha (TNFα), and transforming growth factorbeta (TGFβ) genes were measured; using the real-time polymerase chain reaction (RT-PCR) technique. Our results demonstrated the ability of MSCs to differentiate into adipocyte and osteocyte lineages. Further investigation also displayed that although UCB-MSCs could significantly reduce the expression of pro-inflammatory cytokines like IL2, IL6, IFNγ, and TNFα in activated T-lymphocytes, they noticeably potentiated the expression levels of IL4, IL10, IL13, and TGFβ in the co-culture setting. In conclusion, UCB-MSCs have immunomodulatory effects on activated T-lymphocytes in favor of anti-inflammatory responses.

Because of geographic variation and regional types of allergens, it is recommended that allergists identify common allergens in their area of activity. In the present study, the prevalence of respiratory allergens in patients with asthma and allergic rhinitis was investigated.

This study is descriptive and retrospective. The required data of this study were extracted from the records of 661 patients who were referred to the Asthma and Allergy Clinic of Ardabil University of Medical Sciences (Ardabil province, Northwest of Iran) from April 2016 to March 2017. After confirmation of allergic asthma or rhinitis by the asthma and allergy specialist, these patients were subjected to a prick test with allergen extracts. In the group of grasses the extract of nine grasses, in trees the extract of 11 Tree mix, in weeds the extract of Common weed mix, in animal allergens the three extracts of Standard cat, Dog epithelia, Cockroach mix, in weeds the Mite mix and in fungi, three extracts of Mold mix1, Alternaria and Aspergillus mix were used. All the data were analyzed using SPSS software, version 25.

According to results, of the 661 patients who were studied, 462 ones had positive and 273 had significant prick test results. The grasses group with 293 positive (44.3%) and weeds group with 259 positive results (39.2%) were more common than the other categories. Among the significant positive tests, these two categories with 161 and 142 significant positive tests were indicated as the most common allergens. Respiratory allergens were also more common in patients with a family history of allergies in weeds and trees categories, but there was no significant difference in sensitization pattern according to the history of tonsillectomy.

Patients in Ardabil with allergic rhinitis and asthma were more sensitized to weeds and grass mixtures. It is recommended to provide preventive recommendations to allergic patients and the development of localized skin testing packages and additional studies should be conducted focusing on these two categories of allergens.

The aerial parts of Artemisia marschalliana Sprengel as an indigenous species of genus Artemisia in the East Azerbaijan province of Iran, was subjected to phytochemical analysis, as well asanti-proliferative, free-radical-scavenging and anti-malarialactivities.

The chemical composition of the essential oil obtained from the aerial parts of A. marschalliana was analyzed by GC/MS (gas chromatography/mass spectrometry) and GC/FID (gas chromatography/ flame ionization detector). The anti-proliferative, anti-oxidant, and anti-malarial activities of the essential oil were assessed by MTT, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and cell-free β-hematin formation assays, respectively.

A total of 38 constituents were identified, which represented 95.55% of the oil. The essential oil was characterized by a high content of oxygenated sesquiterpenes. The major components of the oil were spathulenol (38.25%), isoaromadendrene epoxide (8.5%), and caryophyllene oxide (7.31%). The oil exhibited cytotoxic activity against the human breast adenocarcinoma (MCF-7) cell line. The half maximal inhibitory concentration (IC50) of anti-malarial assay was 0.38±0.04 mg/mL; the oil, however, displayed low anti-oxidant activity.

These findings will be beneficial for the further development of new chemotherapeutic or anti-malarial agents.

Scrophularia atropatana (S. atropatana), an Iranian plant belonging to the family of Scrophulariaceae, was assigned for its chemical compositions and biological activities of essential oil (EO) and extracts of the aerial parts of the plant during the flowering stage. Combination of GC-MS and GC-FID was assessed for analyzing the chemical compositions of the EO from the aerial parts of S. atropatana. Furthermore, Brine shrimp lethality test and DPPH assay were performed to evaluate general toxicity and free-radical-scavenging properties, respectively. Furthermore, anti-proliferative and antimicrobial activities were assessed by MTT assay and disc diffusion methods correspondingly. Additionally, all the potent samples (extracts) and its fractions in the MTT assay were further studied for the presence of various compounds by GC-MS apparatus. MeOH extract and 40% sep-pak fraction indicated high amounts of total phenolic (TPC), total flavonoid content (TFC), and antioxidant properties. In the case of general toxicity, among the extracts, dichloromethane (DCM) extract showed noticeable effect. Furthermore, DCM extract was indicated potent ability to eliminate breast tumor cells and minimum efficacy on normal cells. Anti-microbial activity of all samples was ignorable. The potent extracts and fractions which had more anti-proliferative activity were further elucidated by GC-MS and showed high amounts of Alkanes and fatty acids. In the case of EO constituents, non-terpenoids were the major compounds.To sum up, it seems BSLT could be a good preliminary approach for evaluating the cytotoxicity in MCF-7 cell line. Additionally, antioxidant activity, TPC, and TFC contents of all samples were in consistent with each other.

Ankylosing spondylitis (AS), an autoinflammatory disease, has been associated with impaired Endoplasmic reticulum aminopeptidase (ERAP) 1 activity, which is involved in priming antigenic peptides. The purpose of this study was to evaluate if the genetic variant of ERAP1 gene could impress the inflammation status of the AS patients. For genotyping, 140 AS cases and 140 healthy controls were enrolled. After isolation of peripheral blood mononuclear cells (PBMCs) and DNA extraction, all the subjects were genotyped for rs27044 polymorphism using SSP-PCR assay. Total RNA of PBMCs was isolated, cDNA was synthesized, and quantitative analyses of mRNA expression of cytokines were performed via Real-time PCR using the SYBR Green Gene Expression MasterMix. To measure the concentration of cytokines in serum of subjects, Enzyme-linked immunosorbent assay (ELISA) was used. It was observed that the G allele of rs27044 polymorphism was significantly prevalent in AS patients. Moreover, the GG genotype and the GG+GC dominant model had significantly different distribution between study groups. There was a significant overexpression of mRNAs of IL-17A, IL-6, IL-33, TNF-α, and IFN-γ, while IL-10 was significantly downregulated in AS patients. The ELISA results were in line with that of the gene expression analysis. No significant differences in mRNA expression and concentration of cytokine were identified among AS patients with three genotypes for rs27044 SNP. This study replicated the association of polymorphisms in ERAP1 gene with the risk of AS in a population from Iranian. However, it did not directly determine the inflammatory profile of the AS patients.

Breast cancer is the most frequent malignancy diagnosed in women both in developed and developing countries. Natural products especially those from herbal origin have high potential in producing drug components with a source of novel structures. The present study was designed to explore the cytotoxic effects and the cell death mechanism of Scrophularia atropatana extracts.
MTT assay was employed to evaluate the cytotoxic activity of the extracts of S. atropatana on the MCF-7 as well as non-malignant cells. Furthermore, induction of apoptosis was evaluated by TUNEL assay, cell death detection ELISA, DNA fragmentation test, western blotting and Real Time PCR.
In vitro exposures of the MCF-7 cells with different concentration of S. atropatana extract significantly inhibited their growth and viability and induced apoptosis in the MCF7 cells. Cleavage PARP protein, decrease in the mRNA expression levels of bcl-2 and increase expression of Caspase-3 and Caspase-9 mRNA, highlights that the induction of apoptosis was the main mechanism of cell death. Moreover the expression study of Caspase-9 mRNA showed that, the extracts have induced apoptosis via intrinsic mitochondrial pathway.
Our results demonstrated that dichloromethane extract of Scrophularia atropatana has an apoptotic effects and it can be developed as anticancer agents.

The mylonitic granitoids of Gole Gohar, south east of Sirjan, are located in a key area which their study is important for understanding the history of Precambrian basement of Sanandaj- Sirjan zone and its metamorphic and magmatic evolution during the subduction of Neo- Tethys. Field studies show that these granitoids are located in the basement of the metamorphic rocks such as metapelite, calc schist and amphibolite. In this Study the granitoidic intrusions are classified in two types based on lithology and their geochemistry. Type I is garnet- biotite granitoid and type II is hastingsite granitoid. Both of these granites show some evidence of mylonitic fabric, which is more clear in garnet- biotite granitoid. These plutons are Meta aluminous, I Type granitoid and have high K calc-alkaline nature. Based on U-Pb dating of zircon, the age of all granitoids is between 538.6–580.7 Ma (Late Precambrian- Early Cambrian). Based on the results of this study, despite the mineralogical and geochemical differences, all granitoidic intrusions formed in the Precambrian during the Pan African orogeny. The old age of the granitoids is similar to those introduced in other parts of Sanandaj-Sirjan zone that may indicate the presence of Precambrian basement in almost the entire Sanandaj-Sirjan zone.

Cancer is uncontrolled growth of abnormal cells in the body. Nowadays, cancer is considered as a human tragedy and one of the most prevalent diseases in the wide, and its mortality resulting from cancer is being increased. It seems necessary to identify new strategies to prevent and treat such a deadly disease. Control survival and death of cancerous cell are important strategies in the management and therapy of cancer. Anticancer agents should kill the cancerous cell with the minimal side effect on normal cells that is possible through the induction of apoptosis. Apoptosis is known as programmed cell death in both normal and damaged tissues. This process includes some morphologically changes in cells such as rapid condensation and budding of the cell, formation of membrane-enclosed apoptotic bodies with well-preserved organelles. Induction of apoptosis is one of the most important markers of cytotoxic antitumor agents. Some natural compounds including plants induce apoptotic pathways that are blocked in cancer cells through various mechanisms in cancer cells. Multiple surveys reported that people with cancer commonly use herbs or herbal products. Vinca Alkaloids, Texans, podo phyllotoxin, Camptothecins have been clinically used as Plant derived anticancer agents. The present review summarizes the literature published so far regarding herbal medicine used as inducers of apoptosis in cancer.