Interferon-beta (IFN-β) is a cytokine with a wide range of biological and pharmaceutical applications, including multiple sclerosis (MS), cancer, some autoimmune disorders, and viral infectious diseases. Thus, many studies have been performed to develop novel strategies for the high-yield production of functional IFN-β in a cost-effective approach. Here, we aimed to improve the intracellular expression of IFN-β-1a in Pichia pastoris. The gene of IFN-β-1a was successfully sub-cloned into the pPICZA vector. The recombinant vector was transfected to P. pastoris GS115 cells by electroporation. After screening positive P. pastoris transformants, the expression of IFN-β-1a was evaluated and the cultivation conditions, including temperature, time of incubation, and methanol concentration, were optimized. The protein expression levels were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The double digestion with EcoRI and XhoI restriction enzymes and sequence analysis confirmed the correct sub-cloning of the IFN-β-1a gene into pPICZA. SDS-PAGE analysis showed that the highest level of IFN-β-1a (25 mg per 1 L of yeast culture) was produced with 2% methanol at 28°C after 72 h incubation. Optimization of cultivation conditions for intracellular expression of IFN-β-1a was successfully performed. This approach can be generally applied to improve the production yield and quality of other recombinant proteins in P. pastoris.

Advancing age could influence renin angiotensin system components, especially angiotensin type 1 receptor (AT1R). This study examined the effect of AT1R antagonist, losartan, on age-related differences in renal vascular responses to angiotensin II in male and female rats. Forty-eight anesthetized male and female rats (8-12 and 24-28 weeks age ranges) were subjected to catheterize. Then, the responses of mean arterial pressure (MAP), renal perfusion pressure (RPP), renal blood flow (RBF), and renal vascular resistance (RVR) to angiotensin II with or without losartan were determined and evaluated. There were not significant differences in the basal values of MAP, RPP, RBF, and RVR in males. However, it was observed significant difference in RVR in females (P < 0.05). The blockade of AT1R attenuated basal MAP and RPP in all the groups (P < 0.05). The infusion of losartan altered basal RVR and RBF values in female groups (P < 0.05). Moreover, losartan eliminated vasoconstrictor responses to angiotensin II in female groups (P < 0.05). Also, losartan induced significant vascular responses to angiotensin II in male groups (P < 0.05). Losartan could maintain RBF changes in response to angiotensin II in both 8-12- and 24-28-week females. Losartan enhanced the RBF response to angiotensin II in 8-12-week males, but not in 24-28-week males. It seems that females (not males) in various age ranges are resistance against RBF changes by acutely increased angiotensin II.

Aortic stiffness is an independent predictor of cardiovascular events which is increased in rheumatoid arthritis (RA). It can be measured by carotid-femoral pulse wave velocity (cfPWV). Phase angle (PhA) is lower in patients with cardiovascular disease and may be informative in assessing the clinical course of RA. In this observational and cross-sectional study, all RA patients referred to the Imam Khomeini Hospital rheumatology clinic between September 2022 and March 2023 were included in the study. RA activity was assessed using the DAS28 criteria. In the patients, PhA and cfPWV were measured using Inbody-s10 and PulsePen tonometer instruments. The relationships between PhA, cfPWV, clinical course of RA, and CRP were evaluated using regression analysis. 53 patients were included in the study (83% female, mean age 46.5 years). Significant inverse relationships existed between PhA, CRP, and age (P value = 0.003, 0.0001, R: 0.69, respectively). People with aortic stiffness had a lower mean PhA (P value = 0.05). In patients with RA duration of less than 10 years, the cfPWV percentile and the prevalence of rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) positive cases were higher than in patients with RA duration >10 years (P values = 0.02, 0.01, respectively). With increasing duration of RA, aortic stiffness and positive serology cases decreased. PhA and cfPWV may be useful in assessing the clinical course of RA to prevent cardiovascular events.

Hysteroscopy is known as the gold standard for endometrial polyps diagnosis and its findings on vascularity, size, and number of polyps can indicate malignancy, but it is a relatively expensive method with some complications. Ultrasound is a common part of the gynecological examination, and with technological advances, its ability to predict pathological outcomes has increased. This study aimed to determine the accuracy of ultrasound in diagnosing the characteristics of endometrial polyps. This diagnostic value study was performed on 300 premenopausal and postmenopausal women over 40 years of age with endometrial polyps referred to Alzahra and Beheshti hospitals in Isfahan. The characteristics of endometrial polyps were evaluated by transvaginal ultrasonography and hysteroscopy and biopsy specimens were sent for pathological evaluations. In this study, 103 premenopausal women and 197 postmenopausal women were evaluated. Malignancy was confirmed by pathology in 4 premenopausal women (2%) and 2 postmenopausal women (2%). In both hysteroscopy and ultrasound methods, the frequency of vascularity was significantly different in postmenopausal and premenopausal women, but the other features of the polyp were not significantly different in them. Ultrasonic sensitivity in detecting the presence of vascularity, polyps larger than 1.5 mm, more than 1 polyp, and the presence of pedicle were 39.04, 57.38%, 91.93 and 94.95%, respectively, its specificity were 98.94, 36.47, 99.57 and 98.89% respectively. A comparison of the characteristics of polyps in both ultrasound and hysteroscopy methods shows that hysteroscopy has been more effective in diagnosing malignancy and ultrasound has not have acceptable sensitivity in diagnosing size and vascularity.

This study evaluates the effect of misoprostol alone in comparison with misoprostol with Foley catheter in preparing the cervix for induction of labor in women with premature rupture of the amniotic sac. This randomized clinical trial study was performed from 2017 to 2019 on 206 pregnant women with singleton pregnancy and gestational age more than 36 weeks, whose rupture of the amniotic sac had occurred less than 12 hours and had a Bishop score less than 4. These women were randomly assigned to two groups of Foley catheters with misoprostol (intervention group, P = 103) or misoprostol alone (control group, P = 103) to induce labor. In both groups, sublingual misoprostol (25 micrograms) was administered at intervals of 4-6 hours. The collected data were analyzed by SPSS.21 software. There is no significant difference between age and Bishop score in the two groups (P = 0.19, P = 0.31, respectively). Lower doses (0 to 3) of misoprostol were used in the intervention group versus 0 to 5 doses in the control group (P = 0.001). Delivery time was shorter in the intervention group (10.83 hours vs. 13.10 hours in the control group, P = 0.001). Also, the probability of complications such as fever, tachysystole, and hospitalization of an infant in the neonatal intensive care unit (NICU) did not increase. An intracervical Foley catheter with misoprostol is more effective in inducing labor in pregnancies with premature rupture of the membranes than using misoprostol alone and can be a safe and effective option.

Background:Recessive disruptive mutations in nucleotide excision repair genes are responsible for a wide range of cutaneous photosensitivity and, in some cases, are associated with multi-system involvement. The heterogeneous nature of these conditions makes next-generation sequencing the method of choice to detect disease-causing variants.Materials and Methods:A patient from a large multiplex inbred Iranian kindred with several individuals suffering from skin sun-sensitive manifestations underwent complete clinical and molecular evaluations. Whole exome sequencing (WES) was performed on the genomic sample of the proband, followed by bioinformatics analysis. Subsequently, co-segregation of the candidate variant with the condition was performed by Sanger sequencing.Results:A rare homozygous nonsense variant, c.1040G>A (p. Trp347*), was identified in the UVSSA gene, resulting in UV-sensitive syndrome (UVSS) complementation group A. The global minor allele frequency of the variant is < 0.001 in population databases. Tryptophan 347 residue is conserved among mammalians and vertebrates, and the null variant is believed to lead to a truncated protein with cellular mislocalization.Conclusions:Here, we report the first genetic diagnosis of UVSS-A in Iran via the successful application of Next-generation sequencing, which expands our understanding of the molecular pathogenesis of this condition.

Reports of fungal infections have increased over the past decades, making them a major threat to human health. In this study, we review the effects of genetic defects on susceptibility to fungal diseases. To identify all relevant literature, we searched Google Scholar, PubMed, and Scopus and profiled studies published between 2008 and 2021. The results of several studies conducted on this subject have shown the significant effects of genetic variations such as hyper-IgE syndrome, Autoimmune polyendocrinopathy candidiasis ectodermal dystrophy syndrome, dectin-1 deficiency, CARD9 mutations, STAT1 mutations, and IL17 mutationson the host immune system's response, which has an important impact on susceptibility to fungal infections. The underlying immune system-related genetic profile affects the susceptibility of individuals to different fungal infections; therefore, this subject should be further studied for better treatment of fungal diseases.

Hypertension (HTN) is a leading cause of cardiovascular diseases and its control is poor. There is heterogeneity in levels of blood pressure control among various population subgroups. The present study was conducted within the framework of the National Program for Prevention and Control of Cancer, Diabetes, Cardiovascular Diseases, and Stroke (NPCDCS) in India. It aims to estimate the proportion of optimal blood pressure control and identify factors associated with uncontrolled HTN consequent to initial screening. We assembled a cohort of individuals with HTN confirmed in a baseline screening in sixteen urban slum clusters of Bhopal (2017-2018). Sixteen accredited social health activists were trained from within these slums. Individuals with HTN were linked to primary care providers and followed up for the next two years. Obtaining optimal blood pressure control (defined as SBP <140 and DBP <90 mm of Hg) was a key outcome. Of a total of 6174 individuals, 1571 (25.4%) had HTN, of which 813 were previously known and 758 were newly detected during the baseline survey. Two-year follow-up was completed for 1177 (74.9%). Blood pressure was optimally controlled in 301 (26%) at baseline and in 442 (38%) individuals at two years (an absolute increase of 12%; 95% CI 10.2-13.9). Older age, physical inactivity, higher body mass index, and newly diagnosed HTN were significantly associated with uncontrolled blood pressure. We found about six of every ten individuals with HTN were on treatment, and about four were optimally controlled. These findings provide a benchmark for NPCDCS, in terms of achievable goals within short periods of follow-up.

Background:This study investigated the feasibility of channelized hoteling observer (CHO) model in computed tomography (CT) protocol optimization regarding the image quality and patient exposure. While the utility of using model observers such as to optimize the clinical protocol is evident, the pitfalls associated with the use of this method in practice require investigation.Materials and Methods:This study was performed using variable tube current and adaptive statistical iterative reconstruction (ASIR) level (ASIR 10% to ASIR 100%). Various criteria including noise, high-contrast spatial resolution, CHOs model were used to compare image quality at different captured levels. For the implementation of CHO, we first tuned the model in a restricted dataset and then it to the evaluation of a large dataset of images obtained with different reconstruction ASIR and filtered back projection (FBP) levels.Results:The results were promising in terms of CHO use for the stated purposes. Comparisons of the noise of reconstructed images with 30% ASIR and higher levels of noise in rebuilding images using the FBP approach showed a significant difference (P < 0.05). The spatial resolution obtained using various ASIR levels and tube currents were 0.8 pairs of lines per millimeter, which did not differ significantly from the FBP method (P > 0.05).Conclusions:Based on the results, using 80% ASIR can reduce the radiation dose on lungs, abdomen, and pelvis CT scans while maintaining image quality. Furthermore using ASIR 60% only for the reconstruction of lungs, abdomen, and pelvis images at standard radiation dose leads to optimal image quality.

MicroRNAs are a large group of small, non-coding ssRNAs (miRNAs) that have an epigenetically pivotal role in gene expression and other biological processes in cells and can be regarded as capable biomarkers for the early detection and management of cancer. The aim of the present review article is to summarize the evidence for recognizing the molecular mechanism, target genes, and clinical significance of miR-647 in different cancers. Multiple studies have demonstrated that aberrant expression of miR-647 could be found in a variety of malignancies, such as bladder cancer, cervical cancer, colorectal cancer, gastric cancer, glioma, hepatocellular carcinoma, non-small cell lung cancer, ovarian cancer, and prostate cancer have reported, notably, increase or decrease in expression of miR-647 so that it can function as a tumorigenic (oncomiR) or tumor suppressor gene. MiR-647 is effective in the proliferation, migration, and invasion of cancer cells by playing a function in cell cycle pathways. MiR-647 can be a valuable potential biomarker for assessing the extent of cancer, prognosis, and response to therapy and shows great therapeutic efficacy in different solid tumors. Moreover, serum concentrations of miR-647 are directly effective in decreasing overall survival and disease progression. So, an efficient therapeutic target can be the effect on miR-647 expression by antitumor drugs.