مجله علمی دانشگاه علوم پزشکی کردستان
سال بیست و هشتم شماره 4 (پیاپی 127، مهر و آبان 1402)

Retinoic acid (RA) is involved in protecting the intestinal barrier, inducing differentiation, growth and proliferation of epithelial cells. There are several hypotheses about the mechanism of induction of apoptosis by RA, but few studies have been performed on the role of HNF4α and Cdx-2 in intestinal cells. The aim of this study was to evaluate the survival and expression of these two genes following administration of RA in Caco-2 cells as a model of intestinal epithelial cells.

In the present study, Caco-2 cells were used and exposed to retinoic acid at concentrations of 10, 20, and 40 μM for 72 hours. After incubation for 24 and 48 hours, these samples were assigned to evaluate the effects of cytotoxicity by measuring mitochondrial enzyme activity using the MTT method. The expression levels of HNF4α and Cdx-2 genes at the mRNA level were examined by real-time PCR technique.

The results showed that 48 hours after adding 20 and 40 μM RA, the number of cells decreased in a concentration-dependent manner. In the first 24 and 48 hours, the dependence on the expression concentration of the HNF4α gene increased, and in contrast, the expression of the Cdx-2 gene decreased during these hours. Based on the results obtained during the 72 hours of the study, the expression levels of the genes decreased compared to those in the control which was due to the reduction of living cells and disruption of cellular homeostasis.

Use of RA in high concentrations can cause disruption of intestinal homeostasis due to an imbalance between the two genes. Therefore, concentration of retinoic acid derivatives should be selected according to the purpose of treatment.

Conventional treatments have shown little success in cancer treatment. Using antibody fragments conjugated with specific proteins and targeting specific receptors is a new strategy for producing anticancer drugs. Despite the advantages of prokaryotic hosts, protein expression in the form of inclusion bodies (cytoplasmic) has been challenging and leads to subsequent difficulties. Production of proteins as soluble forms will significantly help to solve this problem. The primary purpose of this study was to clone and express Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) conjugated with anti CD20 single chain fragment variable (scFV) region of anti-CD20 antibody as a soluble protein using a small ubiquitin-related modifier (SUMO) fusion protein system in E. coli as a new method for optimal production of anticancer drugs.

Appropriate primers for a previously designed DNA sequence encoding the fusion protein were used to amplify the fragment. The amplified fragment was sub-cloned downstream of the SUMO tag in pSUMO vector. Once confirmed by standard methods, the recombinant plasmid was transformed into E. coli strain BL21 (DE3). Expression was induced by isopropyl β- d-1-thiogalactopyranoside. The expressed proteins were assessed by SDS-PAGE and then isolated by affinity chromatography. Western blotting was used to confirm protein expression.

The results showed the DNA of the recombinant fusion protein was sub-cloned correctly, and the relevant analyses indicated that the expression process was successful. The recombinant fusion protein was confirmed by appropriate analysis.

The production of recombinant proteins in a soluble state in the prokaryotic host E. coli can reduce the costs of the downstream process. Production of soluble antiCD20 scFV-TRAIL fusion protein can be considered a proper method to produce recombinant protein in a soluble state in the E. coli system and can decrease the cost of downstream processes.

Diabetes can adversely affect spermatogenesis. Garden cress plant, known as Lepidium sativum, contains antioxidants. This study aimed to evaluate and compare in vivo antidiabetic activities of hydroalcoholic garden cress seed extract and insulin on diabetic rats.

In this experimental study, diabetes was induced in the animals using streptozotocin (STZ; 60 mg/kg). Fifty rats were divided into five equal groups as follows: Groups 1, nondiabetic rats; group 2, diabetic rats induced by streptozotocin; Group 3, diabetic animals that received streptozotocin plus insulin; and groups 4 and 5 were diabetic rats that received 200 and 400 mg/kg garden cress seed extract respectively by gavage for 4 weeks. At the end of the study, the sperm parameters obtained from the tail of the left epididymis and biochemical parameters were analyzed and compared among the groups. Data were analyzed by one-way ANOVA.

The sperm parameters of the diabetic groups receiving 200 and 400 mg/kg of garden cress extract demonstrated a significant increase in all parameters compared to those of the diabetic control group. Administration of garden cress extract as a powerful antioxidant led to compensation for the streptozotocin toxicity and improved sperm quality.

Administration of the Lepidium sativum seed extract compensated for the Streptozotocin-induced harmful effects. Our findings suggested that use of the garden cress seed extract and insulin therapy may have a potential protective effect on diabetes mellitus.

After lung cancer, breast cancer is the main cause of death from cancer among women. Aromatase is a key enzyme involved in the development of estrogen receptor-positive breast cancer, which catalyzes the final stage of estrogen biosynthesis from the conversion of androstenedione and testosterone, and can be a promising target in the treatment of hormone-dependent breast cancer. In this study, the effects of morin and its analogues on aromatase enzyme were evaluated.

In this descriptive-analytical study, for bioinformatics assessment, the 3D structure of morin analogues (15 compounds), the standard drug (anastrozole) and aromatase enzyme were obtained from PubChem and PDB databases, respectively. Molecular docking studies in relation to the effects of the compounds on the aromatase enzyme were performed using MOE-2014 software. Then the physicochemical properties and biological activity of the compounds were predicted using Swiss ADME, PASS and Swiss Target Prediction browsers.

The findings of the present study showed that morin analogues were non-toxic and favorable in terms of physicochemical properties. Also, all morin analogues were capable of inhibiting the aromatase enzyme. The best docking results belonged to galangin, morin, quercetin and rhamnetin compounds with strong binding energy (-13.90 to -14.79 kcal/mol) compared to anastrozole. The prediction coefficient of biological activities of these compounds was 0.175 to 0.952. Proteases, kinases, oxidoreductases, cytochrome P450 and lyases were the main predicted targets for all proposed compounds in the study.

Based on the results of bioinformatics studies, morin analogues, because of their suitable placement in the active site of the aromatase, provide more effective inhibition than the standard chemical drug and can be good candidates for hormone-dependent breast cancer treatment in the in vitro and in vivo studies.

Covid-19 disease is a global health concern that requires rapid quantitative diagnostic testing. The standard technique for diagnosing SARS-CoV-2 is now REAL-TIME PCR. The aim of this study was to design a sensitive Reverse Transcription Loop-Mediated Isothermal Amplification method for the early identification of SARS-CoV-2.

In this laboratory study, specimens were prepared from the patients by laryngeal, pharyngeal, and nasal swabs and after RNA extraction and cDNA synthesis. SARS-CoV-2 virus was evaluated using the RT-LAMP method. Sensitivity of the  RT-LAMP method was evaluated by primers targeting N and E genes.

In this study, 19 SARS-CoV-2 RNA samples were examined. According to the results of this study turbidity or discoloration of fluorescent dye showed that agarose electrophoresis gel is a more sensitive test. Detection limits for the number of  E gene copy were observed at the dilutions of 10-9 and 10-8 for gel electrophoresis and fluorescent light, respectively. This means detection of 1 copy and 14 copies for the two above-mentioned methods, respectively. However, in the case of the N gene the detection limits, were at the dilutions of 10-10 on the gel and 10-8 by fluorescent light, which indicated detection of 1 copy and 17 copies, respectively. The calculations were performed using the Chiang formula.

The results of this study showed that the LAMP was a simple, fast, sensitive, and specific method for the diagnosis of SARS-CoV-2 that may improve the diagnostic potential in clinical laboratories.

Core needle biopsy (CNB) is less invasive and has fewer side effects compared to surgical procedures, and provides accurate information about the nature of the tumor. The aim of this study was to evaluate the efficacy of CNB in the diagnosis of the cause of lymphadenopathy.

In this study, 153 patients with lymphadenopathy underwent CNB from 2014 to 2018. Immunohistochemistry staining with appropriate markers was performed. Excisional biopsy, clinical and radiological data were evaluated using spss-21 softwere, data were analyzed by one way ANOVA and tukey test (p<0/05).

Diffuse large B-cell lymphoma was more frequent (41%). Histopathological diagnosis of core needle biopsy was correct in 83.23% of the patients,among them 11.11% were confirmed by excisional biopsy and 88.88% by clinical and radiological findings. There was a significant relationship between the mean age of the patients and location of lymphadenopathy (P = 0.02) and also between the mean age and pathology diagnosis (P<0.001). The accuracy, sensitivity, and positive predictive value of CNB were 90%, 100%, and 90%, respectively.

Diagnosis of the cause of lymphadenopathy by CNB was correct in most cases and its diagnostic efficacy was confirmed. The present results recommend CNB as a suitable method without side effects for investigation of the cause of lymphadenopathy.

Methotrexate is an important drug for treatment of rheumatoid arthritis (RA) but is associated with adverse side effects on liver. In this study we evaluated the effect of silymarin on methotrexate induced hepatotoxicity and its analgesic effects in the patients taking this drug.

This study inclouded 58 patients with RA. Patients who had been treated with 2.5 mg methotrexate three times a week for six months were randomly divided into two groups of A and B. Group A received methotrexate and group B treated with 280 mg of silymarin tablets daily (two doses for 2 months) in addition to methotrexate. At baseline (before tests) and after two months, both groups completed the VAS (Visual Analogue Scale) questionnaire and Cr (Creatinine), BUN (Blood Urea Nitrogen), ESR (Erythrocyte Sedimentation Rate), Hemoglobin, WBC (white blood cell), PLT (Platelet) and the liver tests including ALT (Alanine Transaminase) and AST (Aspartate Aminotransferase) were evaluated. We used t-test for data analysis.

In the group B, ALT, AST and ESR, Cr and BUN decreased significantly. Also clinical signs of pain which were indicative of pain intensity were decreased.

Use of silymarin in the patients with RA reduced liver enzymes, liver toxicity and renal complications, which may be due to its antioxidant and cell membrane stabilization properties.

Tissue adhesives are increasingly used instead of sutures or staples to close wounds in modern medicine. It seems that use of tissue adhesives can lead to faster and easier closure of the surgical wounds in comparison to sutures. Moreover, tissue glues have a wide application in the fields of tissue engineering and drug delivery systems. Bio-glue which is a widely used bioadhesive in surgery contains bovine serum albumin and glutaraldehyde, but it has significant tissue toxicity due to the high percentage of glutaraldehyde. Adhesive biocompatibility may improve by using albumin nanoparticles along with less toxic cross-linkers such as polypyrrole.

  Albumin nanoparticles were prepared by coacervation method and then, polypyrrole and glutaraldehyde in different proportions were used to prepare the bioadhesive. The properties of nanoparticles were examined by DLS, zeta potential analysis, FT-IR spectrum, and scanning electron microscopy. The effects of pH and concentration of albumin nanoparticles on gelation time were analyzed and the cytotoxicity of the adhesive was investigated by the MTT technique.

  Among the prepared composites, the shortest gelation time was 20 seconds which belonged to the composite containing both crosslinking agents (pyrrole and glutaraldehyde 3%). The results of MTT assay showed that by reducing the percentage of glutaraldehyde, the toxicity of the adhesive significantly decreased (P <0.0001) compared to the toxicity of adhesive containing 10% glutaraldehyde.

Adhesive prepared by use of polypyrrole and 3% glutaraldehyde had a shorter gelation time and greater biocompatibility than the adhesive containing 10% glutaraldehyde. Therefore, it has the potential to replace other adhesives in the medical clinics.

Fear of childbirth (FOC) is a common problem during pregnancy, with higher prevalence in primiparous women. The present study was designed to determine the effect of cognitive counseling and childbirth preparation classes on the fear of childbirth in primiparous women.

This was an interventional study which included 154 eligible primiparous pregnant women. Participants were divided into cognitive-behavioral counseling, childbirth preparation classes participants, and control groups. In this study we used simple random sampling method. At the beginning of the study and before the initiation of the intervention every group of pregnant woman at  the 20-24 weeks of gestational age completed the demographic questionnaire, Wijima delivery expectation questionnaire and Edinburgh depression assessment scale. After implementation of the intervention and 4 weeks later, the levels of fear and depression in the participants were assessed. We used SPSS v.22 for data analysis.

There were no significant differences among the groups in regard to the mean age, literacy level, gestational age and type of participant's occupation at the baseline. The mean values for fear of childbirth and depression scores were not significantly different among the three groups before the intervention. The fear of childbirth and the depression scores decreased significantly at the end and also one month after the end of the intervention (P=0.001, P=0.01, respectively). Participation in childbirth preparation classes reduced the level of fear and depression in participants, which was not significant.

Cognitive counseling can effectively and significantly reduce women's fear of childbirth and depression during pregnancy. Therefore, inclusion of cognitive counseling in the health care programs of pregnant women can effectively promote the health status of mother and child.

Today, environmental pollution, including water pollution, has become a global issue, and human life is dependent on the safe drinking water. This study aimed at spatial analysis of minerals and heavy metals in drinking water distribution network in Kurdistan Province’s villages.

In this descriptive-analytical study we assessed the concentrations of nitrate, nitrite, total soluble solids, fluoride, arsenic, lead, and cadmium in drinking water of all villages connected to water distribution network (1524 villages) in Kurdistan Province from 2015 to 2017. To describe the concentrations of the studied chemicals, spatial distribution maps were plotted using Arc GIS V. 10.3 software. Other statistical analyses including the analysis of the mean difference of the concentrations of nitrate, nitrite, and total soluble solids in the studied cities were performed by one-way analysis of variance using SPSS V. 22 software.

According to the results of this study, tap water in 1485 villages of Kurdistan Province (97.44%) contained nitrate and the amount of this ion in the drinking water of 31 villages (2.03%) was above the national and WHO standards. The mean concentration of total soluble solids in Bijar City was significantly higher than that in other cities (P <0.001). The mean concentration of fluoride in the drinking water of rural areas of Kurdistan province was 0.19 ± 0.25 mg/l, which was lower than the value determined by national standard of Iran (0.5-1.5 mg/l). The concentrations of arsenic in the tap water of 47 villages of Bijar (23 villages), Qorveh (11 villages), Saqez (7 villages), Dehgolan (5 villages), and Kamyaran (1 village), respectively, were higher than the maximum permitted value.

Continuation of the current trend, especially in agricultural sector and uncontrolled use of groundwater resources in agriculture, will lead to decreased water quality. Therefore, it is necessary to monitor agricultural activities and use of fertilizers.

Extracellular vesicles (EVs) are key players in cellular communication and signaling in the health status and diseases. EVs have rather small size and long half-life upon secretion into circulation. This long half-life along with their immune privileged profile and the ability to carry biotherapeutics to the target cells have made EVs an issue of prominent current interest among scientists as an alternative schedule in cancer therapy.

PubMed and Google scholar were searched for relevant articles from journals with high impact factor. Among 400 articles found, 40 articles met the criteria for interpretation and were selected for descriptive review. Original and review articles published in the last ten years were used in this study.

Tumor-derived EVs can be targeted for reducing cancer cell survival and increasing their apoptosis. They are also applicable for drug delivery to primary or metastatic tumors. An effective approach is to load nanoparticles into EVs for targeting a specific cell type in tumor ecosystem. Their application in nano delivery systems for cancer therapy has been the focus of attention.

The current studies have focused on the possibility of using EVs as biomarkers in several diseases, as targets to be removed for recovery of the patient health, and as vehicles for immunotherapy. In this review article, we discussed the importance of EV suppression or EV-based strategy for targeting solid cancers

The health system's responsiveness to provision of health services displays the ability of the system to meet the non-medical needs of people. The present study aimed to assess Iran's health system responsiveness in providing rehabilitation for people with disabilities (PWD).

This population-based cross-sectional study included 1537 PWD referring to physical rehabilitation centers in all provinces of Iran by using a multistage cluster sampling method in 2019. A valid self-administrated questionnaire was used for data collection. Stata software (version 14.0) was used for data processing and analysis.

The frequency rate of good responsiveness to meet physical rehabilitation needs was 64.5%. The health system's highest and lowest frequency rates of good responsiveness were related to rapid response (74.5%), independence  and participation in decision-making (52.5). Having basic health insurance coverage (OR=1.97, 95% CI:1.20-3.25), severity of disability (OR=2.02, 95% CI:1.14-3.60), economic status of individuals (OR=2.04, 95% CI:1.17-3.56), and household size (OR=0.82, 95% CI:0.72-0.94) were significant determinants in regard to poor responsiveness of the health system.

To maintain and enhance responsiveness and eliminate inequalities, interventions such as expanding the rehabilitation facilities, holding special skills training courses for rehabilitation-related assistants, general practitioners, and health workers, and also, empowering PWD are recommended. Further studies are also recommended to identify the causes of poor responsiveness and take measures that can make the health system more responsible.