The role of bacterial genital infections in spontaneous preterm delivery: a case-control study.

Background: Spontaneous preterm delivery is defined as the beginning of the birth process before the 37th week of pregnancy. The presence of microorganisms in the fetal membranes is accompanied by an increase in the production of prostaglandin, one of the important factors associated with the prevalence of preterm birth. The invasion of microorganisms leads to the production of protease, coagulase, and elastase, which directly stimulate the onset of childbirth. We investigated the role of genital infections in women with preterm birth. Methods: The present case-control study was conducted in the west of Iran on 100 women with spontaneous preterm delivery (following 24 weeks of gestation and before 36 weeks and 6 days) as the case group and 100 women with normal delivery as controls. A questionnaire was applied to collect the data. Polymerase chain reaction and pathological examination of the placenta were performed. Results: The average age in women with normal delivery (30.92 ± 5.10) in women with spontaneous preterm delivery (30.27 ± 4.93). The prevalence of Chlamydia trachomatis, Neisseria gonorrhea, Listeria monocytogenes, and Mycoplasma genitalium infections was zero in both groups. The highest prevalence of Gardnerella vaginalis was 19 (19%) in the case group and Ureaplasma parvum 15 (15%) in the control group. Also, Placental inflammation was zero in controls and 7(7%) in the patient group. There was a significant relationship between Gardnerella vaginalis bacteria and spontaneous preterm delivery. Conclusion: The results of our study showed that except for Gardnerella vaginalis bacteria, there is no significant relationship between the above bacterial infections and spontaneous preterm birth. Moreover, despite the significant reduction in the prevalence of many sexually transmitted infections in this research, it is still suggested to increase the awareness of people, including pregnant women, about the ways it can be transmitted by gynecologists and health and treatment centers.

Histopathological Examination of Lung Necropsy of 11 Patients Who Died Due to COVID-19: A Case Series.

COVID-19 is known to present with acute respiratory distress syndrome pathological manifestations. Studies have shown that patients with COVID-19 can develop diffuse alveolar damage, acute bronchopneumonia, necrotic bronchiolitis, and viral pneumonia. In this study, we investigated 11 cases. Needle necropsies of 11 patients, hospitalized at Tohid and Kowsar hospitals of Kurdistan University of Medical Sciences, with a positive antemortem SARS-CoV-2 (COVID-19) real-time PCR test, were fixated within 3 hours after death in the negative-pressure isolation morgue. The participants included six men (54%) and five women (46%) with a mean age of 73.82±10.58 (52-86) years old. The average hospitalization was 14.27±15.72 days. The results showed interstitial lymphocytic pneumonitis in most of the cases, varied from mild to moderate and up to severe in some cases. In 7 cases, anthracosis was noted, while one case demonstrated anthracosis with fibrosis. The hyaline membrane was reported in two patients. In one case, severe interstitial lymphocytic pneumonia with intra-alveolar exudate with organization, lithiasis, bronchiolitis pattern (BOOP), intra-alveolar hemorrhage, and mild fibrosis were seen. As a result, it is suggested to keep an eye on these pathologies in management of the severe cases of COVID-19 infection.

Elevated interleukin (IL)-6 as a predictor of disease severity among Covid-19 patients: a prospective cohort study.

BACKGROUND: accompanied to the spreading of coronavirus disease 2019 (Covid-19) in the world, identifying factors related to the severity of the disease is one of the interests of physician and medical researchers. We hypothesized that interleukin 6 serum level is associated with severe outcome. METHODS: In this longitudinal prospective cohort study we enrolled 208 confirmed COVID-19 patients who were admitted to the Tohid Hospital (Sanandaj, Iran). Patients were classified into two groups based on IL-6 value in the first day of admission, elevated (n = 107) or not elevated/normal (n = 101), and followed until the occurrence of final outcome (death or discharge from the hospital). Data were analyzed using univariate methods, Chi-squared and independent two sample T test. The relationship between the independent variables and our interesting outcomes were investigated by multiple linear and penalized logistic regression modeling. RESULTS: A total of 208 patients, 51% female and mean age 53.6 ± 16.3 years, including 107 elevated and 101 non-elevated IL-6 patients, were followed. No significant difference was observed between the two groups in demographic and clinical characteristics. Although not significant, logistic regression results showed that the chance of death occurrence among patients with elevated IL-6 are 3.91 times higher. According to the multiple linear regression modeling, elevated IL-6 significantly increased the duration of hospital stay (P = 0.02). Frequency of ICU admission (P = 0.04) and mean of ICU stay (P = 0.8) are also higher in elevated IL-6 group. CONCLUSION: This study revealed that elevated IL-6 is significantly related to prolongation of hospital stay in Covid-19 patients. Although not significant, the occurrence of death among patients who had increased IL-6 in the time of admission was higher than patients with normal or lower serum levels of IL-6.

Physical Development at School Entry in Children with Congenital Hypothyroidism Diagnosed by the National Program of Newborn Screening in Iran.

Background: The newborn screening program for diagnosing and treating children with congenital hypothyroidism (CH) in Iran was established in 2004. Objectives: This study aimed to evaluate the national program's success in maintaining the physical development and anthropometric indexes of children with CH. Methods: This historical cohort study was carried out in five provinces located in five different geographical regions of Iran. The anthropometric indexes, including weight, height, and head circumference of 240 children diagnosed with transient congenital hypothyroidism (TCH) (n = 131) and permanent congenital hypothyroidism (PCH) (n = 109) were measured and compared with those of 240 healthy children aged six. Results: Mean ± standard deviation (SD) of weight, height, and head circumference of children with CH aged six were 20304.8 ± 4457.9 g, 115.6 ± 5.9 cm, and 50.8 ± 1.7 cm, respectively. Mean ± SD of height (116.7 ± 6.1 cm) and head circumference (51.1 ± 1.7 cm) in the control (healthy) group were significantly higher than those of the CH children group (P < 0.05). Mean ± SD weight in the control group (20741.2 ± 4337.3 g) was higher than that in the CH group (20304.8 ± 4457.9 g). However, the difference was not statistically significant (P = 0.3). No significant difference was observed between TCH and PCH children in the subgroup analysis (P > 0.05). Conclusions: Although the mean of anthropometric indexes in CH patients was slightly lower than that in healthy children aged six, the difference between the two groups was insignificant. The physical development of children with CH was evaluated as good. Our results suggested that the newborn screening program for identifying and treating children with CH in Iran may have improved the growth outcomes.

Insights Into The Effects of Amino Acid Substitutions on The Stability of Reteplase Structure: A Molecular Dynamics Simulation Study.

Background: Reteplase (recombinant plasminogen activator, r-PA) is a recombinant protein designed to imitate the endogenous tissue plasminogen activator and catalyze the plasmin production. It is known that the application of reteplase is limited by the complex production processes and protein's stability challenges. Computational redesign of proteins has gained momentum in recent years, particularly as a powerful tool for improving protein stability and consequently its production efficiency. Hence, in the current study, we implemented computational approaches to improve r-PA conformational stability, which fairly correlates with protein's resistance to proteolysis. Objectives: The current study was developed in order to evaluate the effect of amino acid substitutions on the stability of reteplase structure using molecular dynamic simulations and computational predictions. Materials and Methods: Several web servers designed for mutation analysis were utilized to select appropriate mutations. Additionally, the experimentally reported mutation, R103S, converting wild type r-PA into non-cleavable form, was also employed. Firstly, mutant collection, consisting of 15 structures, was constructed based on the combinations of four designated mutations. Then, 3D structures were generated using MODELLER. Finally, 17 independent 20-ns molecular dynamics (MD) simulations were conducted and different analysis were performed like root-mean-square deviation (RMSD), root-mean-square fluctuations (RMSF), secondary structure analysis, number of hydrogen bonds, principal components analysis (PCA), eigenvector projection, and density analysis. Results: Predicted mutations successfully compensated the more flexible conformation caused by R103S substitution, so, improved conformational stability was analyzed from MD simulations. In particular, R103S/A286I/G322I indicated the best results and remarkably enhanced the protein stability. Conclusion: The conformational stability conferred by these mutations will probably lead to more protection of r-PA in protease-rich environments in various recombinant systems and potentially enhance its production and expression level.

CRISPR/Cas9-Induced Fam83h Knock-out Leads to Impaired Wnt/ß-Catenin Pathway and Altered Expression of Tooth Mineralization Genes in Mice.

Background: Dental enamel formation is a complex process that is regulated by various genes. One such gene, Family With Sequence Similarity 83 Member H (Fam83h), has been identified as an essential factor for dental enamel formation. Additionally, Fam83h has been found to be potentially linked to the Wnt/ß-catenin pathway. Objectives: This study aimed to investigate the effects of the Fam83h knockout gene on mineralization and formation of teeth, along with mediators of the Wnt/ß-catenin pathway as a development aspect in mice. Materials and Methods: To confirm the Fam83h-KnockOut mice, both Sanger sequencing and Western blot methods were used. then used qPCR to measure the expression levels of genes related to tooth mineralization and formation of dental root, including Fam20a, Dspp, Dmp1, Enam, Ambn, Sppl2a, Mmp20, and Wnt/ß-catenin pathway mediators, in both the Fam83h-Knockout and wild-type mice at 5, 11 and 18 days of age. also the expression level of Fgf10 and mediators of the Wnt/ß-catenin pathway was measured in the skin of both Knockout and wild-type mice using qPCR. A histological assessment was then performed to further investigate the results. Results: A significant reduction in the expression levels of Ambn, Mmp20, Dspp, and Fgf10 in the dental root of Fam83h-Knockout mice compared to their wild-type counterparts was demonstrated by our results, indicating potential disruptions in tooth development. Significant down-regulation of CK1a, CK1e, and ß-catenin in the dental root of Fam83h-Knockout mice was associated with a reduction in mineralization and formation-related gene. Additionally, the skin analysis of Fam83h-Knockout mice revealed reduced levels of Fgf10, CK1a, CK1e, and ß-catenin. Further histological assessment confirmed that the concurrent reduction of Fgf10 expression level and Wnt/ß-catenin genes were associated with alterations in hair follicle maturation. Conclusions: The concurrent reduction in the expression level of both Wnt/ß-catenin mediators and mineralization-related genes, resulting in the disruption of dental mineralization and formation, was caused by the deficiency of Fam83h. Our findings suggest a cumulative effect and multi-factorial interplay between Fam83h, Wnt/Β-Catenin signaling, and dental mineralization-related genes subsequently, during the dental formation process.

Genetic Regulation of Interleukin-6 and Interleukin-10 in COVID-19 Infection.

Background: The role and regulation mechanisms of the interleukin-6 and 10 (IL6 and IL-10) serum levels and the interaction between CD4+ and CD8+ lymphocytes with SARS-COV-2 IgM and IgG in the context of COVID-19 infection are not fully understood. Methods: This study was conducted on 45 COVID-19 patients and 45 healthy individuals. The IL-6 and IL-10 promoter methylation, IL-6 and IL-10 gene expression, SARS-COV-2 IgM, and IgG antibodies and CD4+ and CD8+ lymphocytes were studied by qMSP-PCR, Real-time PCR, ELISA, and flow cytometry techniques, respectively. Results: The male ratio and mean age of critically ill patients' group were significantly higher in compared to controls (P< 0.05). IL-6 gene expression and serum levels were significantly increased in patients compared to controls (P=0.002, 0.001), but IL-6 promoter methylation was not significantly decreased in patients (P=0.835). The IL-10 promoter methylation and expression were not different between cases and controls (0.326, 0.455), but serum IL-10 levels were higher in patients (P< 0.001). The CD4+ and CD8+ lymphocytes decreased (P< 0.001) and mean SARS-COV-2 IgG increased (P=0.002) in the patients compared to controls. Conclusions: The COVID-19 disease result in severe complications in men and elderly. The serum levels of interleukin-6 and 10 increases in COVID-19 infection, and the gene expression of these two interleukins underlying in this increase. The serum levels of IL-6, IL-10 and SARS-COV-2 IgG as well as CD4+ and CD8+ lymphocyte counts should be investigated to monitor patients and predict the course of disease.

Over-expression of survivin could prevent the oxidative stress and toxicity of rotenone in SH-SY5Y cells.

Objectives: It is important to find novel therapeutic molecular targets for curing Parkinson's disease (PD). Accordingly, this study aimed to evaluate the effect of over-expression of the survivin gene, a gene frequently reported as neuroprotective, on the in vitro model of PD. Materials and Methods: Survivin was over-expressed in SH-SY5Y cells. Next, the cells were treated with rotenone (500 nM) for 24 hr. Then, viability and the total antioxidant capacity were assessed. The expression levels of 15 important genes of key cellular processes (oxidative stress, apoptosis, cell cycle, and autophagy) were assessed. The studied genes included survivin, superoxide dismutase, catalase, BAX, bcl2, caspase 3, caspase 8, caspase 9, p53, SMAC, ß-catenin, mTOR, AMPK, ATG7, RPS18. The apoptosis level and the frequency of cell cycle stages were assessed by flow cytometry. For analyzing the data, the ANOVA test followed by Tukey's test was used to evaluate the significant differences between the experimental groups. P<0.05 was considered significant. Results: Survivin could significantly decrease the rotenone-induced apoptosis in SH-SY5Y cells. The rotenone treatment led to down-regulation of catalase and up-regulation of bax, bcl2, caspase 3, caspase 8, P53, ß-catenin, and ATG7. Survivin could significantly neutralize the effect of rotenone in most the genes. It could also increase the total antioxidant capacity of SH-SY5Y cells. Conclusion: Survivin could prevent the toxic effect of rotenone on SH-SY5Y cells during the development of in vitro PD model via regulating the genes of key cellular processes, including anti-oxidation, apoptosis, cell cycle, and autophagy.

Human Bone Marrow Mesenchymal Stromal Cells Attenuate Tissue Injury and Reduce Inflammation in Experimental Acute Pancreatitis.

Purpose: Acute pancreatitis (AP) which is distinguished by local pancreatic necrosis, followingby systemic organ failure is known as an inflammatory disease. Up to now, there are only a fewtreatment options accessible for patients suffering from AP. In this study, we aimed to examinethe anti-inflammatory capacities of human bone marrow-derived mesenchymal stromal cells(hBM-MSCs) in a detailed AP model experiment. Methods: AP was induced in C57BL/6 mice by intraperitoneal administration of cerulein (100µg/kg/h × 7 doses) at intervals of 1 hour. Then, 2×105 MSCs were infused in the AP mice bytail vein 6 hours after the last cerulein injection. Mice were sacrificed 12 hours following theinjection of hBM-MSC, and blood samples and pancreas tissues were obtained. Results: We first determined the presence of transplanted hBM-MSC in the pancreas of micewith AP, but not the control mice. Our data indicate that administration of hBM-MSCs to micewith AP lead to (i) decreased serum levels of amylase, lipase and myeloperoxidase activities, (ii)downregulation of proinflammatory cytokine, macrophage inflammatory protein 2 (MIP-2), and(iii) upregulation of the anti-inflammatory cytokine, interleukin 10 (IL-10). Moreover, hBM-MSCadministration results in notably attenuated cerulein-induced histopathological alternationsand edema. Conclusion: we demonstrate that hBM-MSC attenuates AP signs and indicating that hMB-MSCtherapy could be a suitable approach for the treatment of inflammatory disease such as AP.

Topical phenytoin administration accelerates the healing of acetic acid-induced colitis in rats: evaluation of transforming growth factor-beta, platelet-derived growth factor, and vascular endothelial growth factor.

Ulcerative colitis (UC), limited to the colon's innermost lining, has become a global health problem. Immunomodulatory and monoclonal antibodies are used to treat UC despite their side effects and limitations. Phenytoin is used to heal wounds owing to its effects on growth factors, collagen, and extracellular matrix synthesis. This study aimed to evaluate the effect of topical phenytoin administration in UC. Phenytoin was administered in two doses during the treatment. Eighty male Wistar rats (230-280 g) were divided randomly into ten groups of sham, control, hydrocortisone, phenytoin 1%, and 3% groups in 6- or 12-day treatment protocols. The UC model was induced by the administration of acetic acid 4% into the colon. Animals were killed on the 7th and 13th postoperative days. The main outcome measures included body weight loss, microscopic score, and ulcer index measured using specific criteria. Growth factors were measured by western blotting. Results illustrated that body weight loss was reversed in the treatment groups. Ulcer index had decreased on 6- and 12-day treatment protocols. Microscopic scores in 6-day enema treatment significantly decreased compared to the control groups. Transforming growth factor-beta (TGFß) significantly increased in a time-dependent manner and platelet-derived growth factor (PDGF) and vascular endothelial growth factor (VEGF) significantly increased in a time- and dose-dependent manner in phenytoin 1% and 3% in the 6- and 12-day protocols. Phenytoin dose- and time-dependently reversed weight loss. In addition, histopathological parameters included microscopic scores, and the ulcer index was decreased through the induction of growth factors TGFß, PDGF, and VEGF and consequently accelerated ulcer healing.

MT2-MMP is differentially expressed in multiple myeloma cells and mediates their growth and progression.

OBJECTIVE: Membrane type-matrix metalloproteinases (MT-MMPs) are known as key regulators of cancer progression/metastasis. However, their roles in the growth and progression of multiple myeloma (MM) have not been yet elucidated. METHODS AND MATERIALS: The expression of 6 MT-MMPs in MM, B cell lines, and normal peripheral blood (PB) cells were measured by RT-PCR, qRT-PCR, flow cytometry, western blotting, and immunocytochemistry. B lymphocytes, CD19-/CD138-, and CD19-/CD138+ cells, known as malignant plasma cells (MPC), were sorted from bone marrow (BM) aspirations of 10 MM patients, and MT2-MMP expression was examined in these cells using qRT-PCR, flow cytometry and immunohistochemistry, and western blotting. Moreover, the expression of MT2-MMP in BM biopsies from 13 normal individuals and 14 MM patients was analyzed by immunohistochemistry. MT2-MMP was also knocked down in U266 cells using siRNA technology and the adhesion, invasion, migration abilities, and cell proliferation were determined and compared with scrambled ones in both in vitro and in vivo studies. RESULTS: Our results showed that MT2-MMP expression is significantly higher in MM cell lines and MPC cells than B cell lines and other PB- or BM-derived cells. MT2-MMP is expressed in BM biopsies from all 14 patients with MM, and 67.85% ± 32.38 of BM cells were positive for MT2-MMP. In contrast, only 0.38 ± 0.76 of BM biopsies from normal individuals were positive for MT2-MMP. Importantly, MT2-MMP was expressed in all the patients' BM biopsies at the diagnosis, but not in the remission phase. MT2-MMP siRNA significantly decreased adhesion, invasion, migration, and 3D cell proliferation of U266 cells. Moreover, in the xenographic model, MT2-MMP siRNA prevented the growth and development of plasmacytoma. Taken together, these data demonstrate that MT2-MMP is strongly expressed in MM cells and plays important role in the growth and progression of these cells, suggesting that MT2-MMP is an appropriate biomarker in diagnosis and therapeutic interventions of MM.

Association between trace elements in cancerous and non-cancerous tissues with the risk of breast cancers in western Iran.

This study aimed to assess the tissue content of essential and toxic metals including lead (Pb), cadmium (Cd), arsenic (As), silver (Ag), aluminum (Al), chromium (Cr), copper (Cu), iron (Fe), selenium (Se), and zinc (Zn) in the breast cancerous tissues compared to the non-cancerous tissue. The biopsy specimens of 63 breast cancers along with 63 adjacent healthy tissues in Kurdistan Province, Iran, were collected from 2019 to 2020 and assayed using ICP-MS (Agilent 7900). The results of the Mann-Whitney test illustrated that the concentration of Pb, Cd, As, Cr, Cu, and Se were significantly elevated in cancerous tissue (p < 0.05), while Zn was the only trace element with higher levels in healthy subjects (p < 0.05). Moreover, weak to moderate correlations between elements were observed in the cancerous group including Al-Cr (r=0.60), As-Cu (r=0.52), and Cu-Se (r=0.56). In contrast, no correlation over 0.50 was found between trace elements in the non-cancerous group. Raw risk differences (RDs) accounted for a significant effect for Pb, Cd, As, Ag, Cr, Se, and Zn on the development of breast cancer. In conclusion, elevated levels of As, Cd, Cu, Pb, and Se may contribute to enhancing the risk of breast cancer.

Oral Administration of Probiotic Enterococcus durans to Ameliorate Experimental Autoimmune Encephalomyelitis in Mice.

Introduction: Probiotics, including lactobacilli, have immunomodulatory activities with promising effects on inflammatory diseases. In this study, we evaluate the effect of Enterococcus durans (Edu) and three various strains of lactobacilli (Lacto-mix), including L. rhamnosus, L. casei, and L. plantarum, to prevent Experimental Autoimmune Encephalomyelitis (EAE) features. Methods: C57BL/6 female mice were inoculated with Myelin Oigodendrocyte Glycoprotein (MOG35-55) in CFA (complete Freund's adjuvant) to induce EAE. Five groups (n=6 in each group) of animals received saline or probiotics by oral gavage with 200 µL of lactobacilli (1.5×108 CFU/mL) for 2 weeks before the immunization and during the test for one month. Results: Histopathological studies showed an increase in infiltration of inflammatory cells and destruction of the myelin membrane in the EAE group but a decrease in inflammatory cells in the probiotic-treated animals. Pro-inflammatory cytokines (Interleukin [IL]-17 and Interferon [IFN]-γ) concentration in the supernatant of the brain and spinal cord tissues showed a significant increase in the EAE compared with the normal saline group (P<0.01). While in the spinal cord tissue, there was a decrease in IL-17 in those animals treated with the Lactomix and Edu + Lacto-mix (P<0.01) and a significant decrease in IFN-γ in those animals that received Edu (P<0.05). Western blot analysis of matrix metalloproteinase-9 and myelin basic protein showed a decrease and increase in treatment and EAE groups, respectively, compared to the normal control group. Conclusion: Our data suggest that probiotic Enterococcus durans and Lacto-mix prevents EAE, but further studies are needed to clarify the exact mechanisms and their application in preclinical and clinical trials. Highlights: Dysfunction of the blood-brain barrier, migration of inflammatory cells into the Central Nervous System (CNS), and an increase in the pro-inflammatory factors, are the hallmarks in the pathogenesis of Multiple Sclerosis (MS) and Experimental Autoimmune Encephalomyelitis (EAE).The optimal effects of probiotic strains may involve the simultaneous use of more than one strain.Probiotic Enterococcus durans and Lacto-mix have a preventive effect against EAE. Plain Language Summary: Multiple Sclerosis (MS) is a myelin-degenerating autoimmune disease in the central nervous system. Experimental Autoimmune Encephalomyelitis (EAE), due to its similar clinical and pathologic features to MS, is widely used in many model studies of this disease. The microbiome refers to a genomic set of germs (bacteria, arches, fungi, and viruses), a commensal flora that lives in the intestine and niche of humans and other mammals. The microbiome affects the host's physiological system, especially the balance between health and disease. Additionally, the importance of the microbiome is evident in regulating the intestine-brain axis, or the coordination of the digestive and the central nervous system. In this regard, probiotics, including lactobacilli, have antioxidant and anti-inflammatory properties in vitro and in vivo. Probiotic strains have a wide range of health-improvement effects, and a combination of strains with specific properties provides a broader range of antimicrobial spectrum and stronger anti-inflammatory effects. Considering the critical role of probiotics in the immune system, this study aimed to investigate the possible role of Enterococcus durans alone or in combination with Lactobacillus mixture (L. rhamnosus, L. casei, and L. plantarum) on the EAE animal model of MS.

In vitro effects of pentoxifylline and coenzyme Q10 on the sperm of oligoasthenoteratozoospermia patients.

The effect of in-vitro sperm incubation with Pentoxifylline (PTX) and Coenzyme Q10 (CoQ10) in Oligoasthenoteratozoospermia (OAT) patients was evaluated. Semen samples were obtained from men with Normozoospermia and men with OAT. Motile sperm from the two groups were subdivided into four subgroups: (i) without incubation with PTX + CoQ10; (ii) incubation with PTX; (iii) Incubation with CoQ10; and (iv) incubation with a combination of PTX + CoQ10. Then, sperm parameters, chromatin, DNA and membrane integrity, protamine deficiency, apoptosis, mitochondrial activity, sperm chromatin dispersion test (SCD), hypo-osmotic swelling test (HOS), chromomycin A3 (CMA3), Terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL), and diaminobenzidine (DAB) assays were evaluated, respectively. Sperm incubated with CoQ10 and a combination of CoQ10 and PTX resulted in a significant increase in the sperm parameters. Also, a significant decrease was noted with a combination of PTX and CoQ10 in normal men. There was a significant difference between CoQ10 treated and CoQ10 + PTX treated groups in comparison with the OAT group in the percentage of the DNA fragmentation, sperm apoptosis, AB+, HOS test + and sperm mitochondrial activity. Incubated sperm with CoQ10, PTX, and in combination with each other can improve sperm parameters in OAT patients.

Effect of sperm selection methods on ICSI outcomes in patients with oligoteratzoospermia.

OBJECTIVE: Sperm selection without - or with a low level of - protamine deficiency and DNA fragmentation is a remarkable indicator to increase the success rate of ICSI outcomes. The aim of this study was to compare sperm selection methods in the elimination of sperm with protamine deficiency and DNA fragmentation and their effects on ICSI Outcomes in oligoteratzoospermia patients. METHODS: Semen samples were obtained from oligoteratozoospermia patients undergoing ICSI. Sperm selection was conducted using Zona Pellucida (ZP) binding, Hyaluronic Acid (HA) binding, and conventional PVP methods. SCD assay and CMA3 staining were used for the detection of sperm protamine deficiency and DNA fragmentation. Good quality of the embryo, blastocyst formation, chemical, and clinical pregnancy rates among studied groups was evaluated and compared. RESULTS: Our results indicated the percentage of sperm DNA fragmentation and protamine deficiency were lower significantly in the HA- and ZP-bound sperm. Although no significant differences were observed in the fertilization rate among studied methods, good quality of cleavage embryo rates were increased using ZP and HA methods versus the conventional PVP method. However, there were no significant differences in cleavage and embryo quality between the HA compared to the ZP method. Blastocyst formation, chemical and clinical pregnancy rates increased in the HA method. CONCLUSIONS: Overall, the HA method for sperm selection due to high sensitivity in selecting sperm with a low level of DNA fragmentation and protamine deficiency is a very useful method to increase the success rate of ICSI outcomes in oligoteratozoospermia patients.

Combination of C21 and ARBs with rhACE2 as a therapeutic protocol: A new promising approach for treating ARDS in patients with coronavirus infection.

Background: Coronavirus disease 2019 (COVID-19) is caused by a new severe acute respiratory syndrome Coronavirus. COVID-19 patients are at risk for acute respiratory distress syndrome and death from respiratory failure. Methods: In this study the complete genome of the SARS-CoV-2 reference sequence, geologically isolated types, and Coronavirus related to human diseases were compared by the Molecular Phylogenetic Maximum Likelihood method. The secondary and tertiary structures of the main protease of SARS-CoV were defined as the most similar viruses to SARS-CoV-2, aligned with chimera software. Therefore, considering ineffective antiviral medications used for SARS-CoV and the importance of preventing acute respiratory distress syndrome as the main cause of mortality, 2 strategies were adopted to acquire the most effective drug combination. Results: The results of phylogenic analysis showed that SARS-CoV is the most similar virus to SARS-CoV-2. The secondary structure and superimposing of tertiary structure did not show a significant difference between SARS and SARS-CoV-2 3C-like main protease and the root means square deviation between Cα atoms did not support the difference between the 2 protein structures. Thus, these 2 mechanisms were fostered in accordance with the correlation between acute respiratory distress syndrome-related Coronavirus, angiotensin-converting enzyme 2 on one side and the possible treatments for reducing the respiratory side effects on the other. The analysis of renin-angiotensin system as well as the tested drugs applied to acute respiratory distress syndrome cases, indicated that angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors, and C21 as nonpeptide agonist might possess a promising modality of treatment for acute respiratory distress syndrome. Furthermore, implementing recombinant human ACE2 as a competitive receptor might be an effective way to trap and chelate the SARS-CoV-2 particles. Conclusion: The data suggest that combination therapy of angiotensin II receptor blockers and C21 could be a potential pharmacologic regimen to control and reduce acute respiratory distress syndrome. Moreover, rhACE2 can be recommended as an effective protective antiviral therapy in the treatment of COVID-19 and its complications.

A Success Story: Review of the Implementation and Achievements of the National Newborn Screening Program for Congenital Hypothyroidism in Iran.

CONTEXT: Today, newborn screening for congenital hypothyroidism (CH) as one of the significant achievements in preventive medicine is integrated into the health systems of many countries worldwide. The national newborn screening for early identification of CH disorder in Iran was established in 2004. The purpose of this study was to review the national newborn screening for CH and its achievements in Iran. EVIDENCE ACQUISITION: In this study, we reviewed the structures, processes, main indicators, and achievements during the 15 years of implementing the national neonatal screening program for the diagnosis and treatment of CH in Iran. RESULTS: Primary TSH measurement with backup thyroxine (T4) determination in infants with high TSH levels was used as the screening strategy in Iran. The coverage of this screening program was higher than 98%. By the end of 2017, 1,501,624 neonates were screened, among which 40,773 were diagnosed with CH and treated based on the national guidelines. The average incidence rate of CH during these years was approximately 2.6:1,000 live births. CONCLUSIONS: The performance of the newborn screening program for congenital hypothyroidism in Iran is favorable, with over a 95% coverage rate. Due to the high recall rate and incidence rate of CH, it is essential to monitor the screening program in the country and also to conduct further studies to determine the main risk factors for the high recall rate and incidence of this congenital error.

Designing new generation of potent inhibitors against membrane-type matrix metalloproteinase-2: a computational effort against multiple myeloma.

Matrix metalloproteinases (MMPs) play important roles in cancer progression and, despite their inhibitors have failed in the clinical trials, they have always been considered as suitable targets for the treatment of tumor. We have recently shown that membrane type (MT) 2-MMPs, is selectively expressed in multiple myeloma (MM) cells and mediates the metastatic characteristics of these cells. In this study, we designed efficient inhibitors against MT2-MMP using state-of-art molecular modeling methods. First, the 3D structure of MT2-MMP was predicted. Then, the proposed potent inhibitors against two regions of the catalytic domain of MT2-MMP (active site and MT-LOOP) were identified through molecular docking, QM-MM and molecular dynamics simulations from a set of compounds in Analyticon library, IBS library, Maybridge screening fragment library and drugbank library. Moreover, ADME estimation showed that pharmacokinetic properties of inhibitors are in the acceptable range for humans. Finally, our data suggested that compounds 'structures.722' (dobutamine) and 'M2' are suitable candidates to inhibit MT2-MMP for further examination in the laboratory.Communicated by Ramaswamy H. Sarma.

Expression of CXC Chemokine Receptors in Acute Ulcerative Colitis: Initial Study from an Animal Model.

BACKGROUND: Ulcerative colitis (UC) is an inflammatory disease which is characterized by infiltration of inflammatory cells, crypt abscesses, distortion of the mucosal glands, and goblet cell depletion. The existence of neutrophil-rich inflammation in colon tissues of patients with UC is one of the most significant histological features of this disease. Nonetheless, the expression of CXCR chemokine receptors which appear as the main chemical mediators governing the migration of neutrophils into the mucosal tissue of patients with UC has not been well clarified. MATERIALS AND METHODS: In this experimental study, the UC model was induced in Wistar rats by administration of 2 ml 4% acetic acid into the large colon through the rectum. Animals were anesthetized after 48 h; their colon tissue samples were isolated for macroscopic and histopathological examination. The expression of receptor1-7 of CXC chemokine was assessed by quantitative reverse transcription-polymerase chain reaction (qRT-PCR) technique. RESULTS: Heavy infiltration of neutrophils, coagulative necrosis, and ulcers were observed in H and E staining, which pathologically proved the UC model. qRT-PCR results indicated that CXCR2 as one of the important ELR+ chemokine family receptors bears the highest expression in the UC group (32 fold) than the control group (P ≤ 0.05). In addition, other CXCRs of this group including CXCR1 did not possess any change (P > 0.05). In contrast, RLR negative chemokine family receptors did not show any changes with the normal group. CONCLUSION: The results showed that CXCR2 is the only receptor for CXCL family which was remarkably upregulated in experimental UC and that CXCR2 might play a significant role in the pathogenesis of UC.

The association between circulating 25-hydroxyvitamin D and cardiovascular diseases: a meta-analysis of prospective cohort studies.

BACKGROUND: There is a controversy about the association between vitamin D and cardiovascular diseases (CVDs). The effect of serum 25-OH-vitD on the risk of CVDs was evaluated. METHODS: Major electronic databases including Scopus, Science Direct, and PubMed were searched. All prospective cohort studies on the relationship between vitamin D status and CVDs conducted between April 2000 and September 2017 were included, regardless language. The study participants were evaluated regardless of their age, sex, and ethnicity. The Newcastle-Ottawa Scale was used to assess the quality of the studies. Two investigators independently selected the studies and extracted the data. The designated effects were risk ratio (RR) and hazard ratio (HR). The random effects model was used to combine the results. RESULTS: A meta-analysis of 25 studies with 10,099 cases of CVDs was performed. In general, a decrease in the level of vitamin D was associated with a higher relative risk of CVDs (incidence-mortality combined) (RR = 1.44, 95% CI: 1.24-1.69). This accounts for 54% of CVDs mortality rate (RR = 1.54, 95% CI: 1.29-1.84(. However, no significant relationship was observed between the vitamin D status and incidence of CVDs (RR = 1.18, 95% CI: 1-1.39). In general, low serum vitamin D level increased the risk of CVD by 44% (RR = 1.44, 95% CI: 1.24-1.69). It also increased the risk of CVD mortality (RR = 1.54, 95% CI: 1.29-1.84) and incidence rates (RR = 1.18, 95% CI: 1-1.39). CONCLUSIONS: The findings showed that vitamin D deficiency increases the CVDs mortality rate. Due to the limited number of studies on patients of the both genders, further research is suggested to separately evaluate the effect of vitamin D status on CVD in men and women.