Interferon-γ Induces Interleukin-6 Production and Alpha-smooth Muscle Actin Expression in Systemic Sclerosis Fibroblasts.

Systemic sclerosis (SSc) is an autoimmune systemic disease that is characterized by immune dysregulation, inflammation, vasculopathy, and fibrosis. Tissue fibrosis plays an important role in SSc and can affect several organs such as the dermis, lungs, and heart. Dysregulation of interferon (IFN) signaling contributes to the SSc pathogenesis and interferon regulatory factor 1 (IRF1) has been indicated as the main regulator of type I IFN. This study aimed to clarify the effect of IFN-gamma (-γ) and dexamethasone (DEX) on the IRF1, extracellular signal-regulated kinase 1/2 (ERK1/2), and the expression of alpha-smooth muscle actin (α-SMA) in myofibroblasts and genes involved in the inflammation and fibrosis processes in early diffuse cutaneous systemic sclerosis (dcSSc). A total of 10 early dcSSc patients (diffuse cutaneous form) and 10 unaffected control dermis biopsies were obtained to determine IFNγ and DEX effects on inflammation and fibrosis. Fibroblasts were treated with IFNγ and DEX at optimum time and dose. The expression level of genes and proteins involved in the fibrosis and inflammation processes have been quantified by quantitative real-time PCR (RT-qPCR) and western blot, respectively. IFNγ could up-regulate some of the inflammation-related genes (Interleukin-6; IL6) and down-regulate some of the fibrosis-related genes (COL1A1) in cultured fibroblasts of patients with early dcSSc compared to the untreated group. Besides, it has been revealed that IFNγ can induce fibroblast differentiation to the myofibroblast that expresses α-SMA. Concerning the inhibitory effect of IFNγ on some fibrotic genes and its positive effect on the inflammatory genes and myofibroblast differentiation, it seems that IFNγ may play a dual role in SSc.

Evaluation of core decompression outcome in systemic lupus erythematosus with hip osteonecrosis: a retrospective cohort study.

BACKGROUND: Osteonecrosis is a major cause of morbidity for patients with systemic lupus erythematosus (SLE). Although core decompression is an approved and trusted technique to prevent further joint deterioration, this surgical method seems to be less beneficial for SLE patients. We aimed to evaluate the outcomes of core decompression in SLE patients with primary stages of femoral head osteonecrosis. METHODS: In this study, 23 patients (39 affected hip joints) with osteonecrosis of the femoral head with stage II of the disease, based on the Ficat-Arlet classification system, underwent core decompression. Also, patients demographic characteristics, clinical data, medication history, comorbidities, immunological findings, hip plain radiographs, history of total hip arthroplasty after core decompression, and patients satisfaction with joint function according to the Oxford hip score questionnaire were obtained. RESULTS: In the study, 53.8% of affected joints showed signs of radiographic deterioration in follow-up imaging. Sixty-one and a half percent (61.5%) of patients had unsatisfactory joint performance. A third (33.3%) of affected hip joints underwent total hip arthroplasty up to 5 years from core decompression. SLE patients with a history of receiving bisphosphonate were 83.2% less dissatisfied with their joint function than patients without a history of bisphosphonate use (P < 0.02). Of the 23 studied cases, the mean cumulative dose of prednisolone before and after core decompression surgery was 46.41 mg and 14.74 mg respectively. Besides, one case (2.6%) that had a high anti-phospholipid antibodies level during follow-up did not have any radiographic deterioration, and 9 cases (23.1%) had some degrees of radiographic deterioration. CONCLUSIONS: The patients group that used bis-phosphonate, had a higher level of satisfaction with joint function after core decompression. Patients with high-level anti-phospholipid antibodies are related to a poor prognosis after core decompression.

Evaluation of core decompression outcome in systemic lupus erythematosus with hip osteonecrosis: a retrospective cohort study

Abstract Background Osteonecrosis is a major cause of morbidity for patients with systemic lupus erythematosus (SLE). Although core decompression is an approved and trusted technique to prevent further joint deterioration, this surgical method seems to be less beneficial for SLE patients. We aimed to evaluate the outcomes of core decompression in SLE patients with primary stages of femoral head osteonecrosis. Methods In this study, 23 patients (39 affected hip joints) with osteonecrosis of the femoral head with stage II of the disease, based on the Ficat-Arlet classification system, underwent core decompression. Also, patients demographic characteristics, clinical data, medication history, comorbidities, immunological findings, hip plain radiographs, history of total hip arthroplasty after core decompression, and patients satisfaction with joint function according to the Oxford hip score questionnaire were obtained. Results In the study, 53.8% of affected joints showed signs of radiographic deterioration in follow-up imaging. Sixty-one and a half percent (61.5%) of patients had unsatisfactory joint performance. A third (33.3%) of affected hip joints underwent total hip arthroplasty up to 5 years from core decompression. SLE patients with a history of receiving bisphosphonate were 83.2% less dissatisfied with their joint function than patients without a history of bisphospho-nate use (P < 0.02). Of the 23 studied cases, the mean cumulative dose of prednisolone before and after core decompression surgery was 46.41 mg and 14.74 mg respectively. Besides, one case (2.6%) that had a high anti-phospholipid antibodies level during follow-up did not have any radiographic deterioration, and 9 cases (23.1%) had some degrees of radiographic deterioration. Conclusions The patients group that used bis-phosphonate, had a higher level of satisfaction with joint function after core decompression. Patients with high-level anti-phospholipid antibodies are related to a poor prognosis after core decompression.

Ras family signaling pathway in immunopathogenesis of inflammatory rheumatic diseases.

The Ras (rat sarcoma virus) is a GTP-binding protein that is considered one of the important members of the Ras-GTPase superfamily. The Ras involves several pathways in the cell that include proliferation, migration, survival, differentiation, and fibrosis. Abnormalities in the expression level and activation of the Ras family signaling pathway and its downstream kinases such as Raf/MEK/ERK1-2 contribute to the pathogenic mechanisms of rheumatic diseases including immune system dysregulation, inflammation, and fibrosis in systemic sclerosis (SSc); destruction and inflammation of synovial tissue in rheumatoid arthritis (RA); and autoantibody production and immune complexes formation in systemic lupus erythematosus (SLE); and enhance osteoblast differentiation and ossification during skeletal formation in ankylosing spondylitis (AS). In this review, the basic biology, signaling of Ras, and abnormalities in this pathway in rheumatic diseases including SSc, RA, AS, and SLE will be discussed.

The role of endothelin and RAS/ERK signaling in immunopathogenesis-related fibrosis in patients with systemic sclerosis: an updated review with therapeutic implications.

Systemic sclerosis (SSc) is a disease of connective tissue with high rate of morbidity and mortality highlighted by extreme fibrosis affecting various organs such as the dermis, lungs, and heart. Until now, there is no specific cure for the fibrosis occurred in SSc disease. The SSc pathogenesis is yet unknown, but transforming growth factor beta (TGF-ß), endothelin-1 (ET-1), and Ras-ERK1/2 cascade are the main factors contributing to the tissue fibrosis through extracellular matrix (ECM) accumulation. Several studies have hallmarked the association of ET-1 with or without TGF-ß and Ras-ERK1/2 signaling in the development of SSc disease, vasculopathy, and fibrosis of the dermis, lungs, and several organs. Accordingly, different clinical and experimental studies have indicated the potential therapeutic role of ET-1 and Ras antagonists in these situations in SSc. In addition, ET-1 and connective tissue growth factor (CTGF) as a cofactor of the TGF-ß cascade play a substantial initiative role in inducing fibrosis. Once initiated, TGF-ß alone or in combination with ET-1 and CTGF can activate several kinase proteins such as the Ras-ERK1/2 pathway that serve as the fundamental factor for developing fibrosis. Furthermore, Salirasib is a synthetic small molecule that is able to inhibit all Ras forms. Therefore, it can be used as a potent therapeutic factor for fibrotic disorders. So, this review discusses the role of TGF-ß/ET-1/Ras signaling and their involvement in SSc pathogenesis, particularly in its fibrotic situation.

Single nucleotide polymorphisms located in TNFA, IL1RN, IL6R, and IL6 genes are associated with COVID-19 risk and severity in an Iranian population.

Cytokines play pivotal functions in coronavirus disease 2019 (COVID-19) pathogenesis. However, little is known about the rationale and importance of genetic variations associated with immune system responses, so-called "immunogenetic profiling." We studied whether polymorphisms of IL6, IL6R, TNFA, and IL1RN affect the disorder severity and outcome in patients infected with COVID19. We recruited 317 hospitalized patients with laboratory-confirmed COVID-19 from Bu-Ali hospital and 317 high-risk participants who had high exposure to COVID-19 patients but with a negative real-time-polymerase chain reaction (PCR) test. Multiple regression analyses were applied. We indicated that participants carrying the A allele in TNFA-rs361525, G>A (p < .004), the C allele in IL1RN-rs419598 T>C (p < .004), the A allele in IL6R-rs2228145, A>C (p = .047) are more susceptible to develop COVID-19. In contrast, those who carry the G allele of IL6-rs2069827, G>T (p = .01), are more protected from COVID-19. Also, we compared the various genotypes regarding the disorder severity and poor prognosis; we found that the AA genotype in TNFA is related to more aggressive illness and bad prognostic in contrast to the other inflammatory cytokines' genotypes. In addition, a high level of inflammatory indications, such as neutrophil-to-lymphocyte ratio and systemic immune-inflammation index, was observed in deceased patients compared with the survived subjects (p < .0001). We advised considering inflammatory cytokines polymorphisms as the main item to realize the therapeutic response against the acute respiratory distress syndrome induced by the SARS-CoV-2 virus.

Association of TMPRSS2 Gene Polymorphisms with COVID-19 Severity and Mortality: a Case-Control Study with Computational Analyses.

Coronavirus disease 2019 (COVID-19) is a severe disease caused by a new variant of beta-coronavirus that first appeared in China. Human genetic factors, including polymorphisms, serve pivotal roles in the high transmission of SARS-CoV-2 and the stubbornly progressing sickness seen in a small but significant percentage of infected people; however, but these factors remain ill-defined. A total of 288 COVID-19 patients and 288 controls were genotyped for TMPRSS2 polymorphisms using both restriction fragment length polymorphism polymerase chain reaction (RFLP-PCR) and amplification refractory mutation system (ARMS)-PCR techniques. Different genotypes of TMPRSS2 polymorphisms were compared in terms of disease susceptibility and mortality. The statistical analysis showed that minor alleles of all studied variants statistically increased the risk of COVID-19, except for the rs75603675 C > A variant. The T allele of rs12329760 conferred an increased risk of COVID-19. Moreover, the AG/AC/TT/AG combination of genotypes significantly enhanced the risk of COVID-19 in our population. Different haplotypes of rs17854725/rs75603675/rs12329760/rs4303795 polymorphisms, including GACA, GACG, GATG, GATA, AATA, ACCG, ACTG, ACTA, GCCA, and GCTG, were found to be associated with increased risk of the disease (odds ratio > 1). Regarding the clinical and paraclinical characteristics, a statistically significant difference was found between non-severe and severe forms except for gender, platelet, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and underlying diseases. In addition, case genotypes of TMPRSS2 rs17854725 A > G, rs12329760 C > T, and rs4303795 A > G were significantly different regarding severe and non-severe forms of the disease (P-value < 0.001). Specifically, death was more frequent in carriers of the AG genotype of rs17854725 A > G (P-value = 0.022). Patients who carry the minor alleles of the four studied TMPRSS2 variants were rather vulnerable to COVID-19 infection. Our findings indicated that rs17854725 A > G (AA vs. AG and AA vs. GG), rs12329760 C > T (CC vs. CT and CC vs. TT), and rs4303795 A > G (AA vs. AG) genotypes of TMPRSS2 variations are associated with a more invasive disorder pattern. More studies on larger populations are needed to confirm our results.

Association of polymorphisms in tumor necrosis factors with SARS-CoV-2 infection and mortality rate: A case-control study and in silico analyses.

The present coronavirus disease 2019 (COVID-19) is spreading rapidly and existing data has suggested a number of susceptibility factors for developing a severe course of the disease.  The current case-control experiment is aimed to study the associations of genetic polymorphisms in tumor necrosis factors (TNFs) with COVID-19 and its mortality rate. A total of 550 participants (275 subjects and 275 controls) were enrolled. The tetra-amplification refractory mutation system polymerase chain reaction technique was recruited to detect -308G>A TNFα and +252A>G TNFß polymorphisms among the Iranian subjects. We demonstrated that carriers of the G allele of TNFß-252A/G, rs909253 A>G were more frequent in COVID-19 subjects compared to the healthy group and this allele statistically increased the disease risk (odds ratio [OR] = 1.55, 95% confidence interval [CI] = 1.23-1.96, p < 0.0001). At the same time, the A allele of TNFα-311A/G, rs1800629 G>A moderately decreased the risk of COVID-19 (OR = 0.68, 95% CI = 0.53-0.86, p < 0.002). Also, we analyzed the various genotypes regarding the para-clinical and disorder severity; we found that in the AA genotype of TNFß-252A/G (rs909253 A>G), the computed tomography scan pattern was different in comparison to cases carrying the AG genotype with p1 < 0.001. In addition, in the severe cases of COVID-19, leukocyte and neutrophil count and duration of intensive care unit hospitalization in the deceased patients were significantly increased (p < 0.001). Moreover, the TNFα-311A/G (rs1800629 G>A) variant is likely to change the pattern of splicing factor sites. Our findings provided deep insights into the relationship between TNFα/TNFß polymorphisms and severe acute respiratory syndrome coronavirus 2. Replicated studies may give scientific evidence for exploring molecular mechanisms of COVID-19 in other ethnicities.

Association of IL-1ß, NLRP3, and COX-2 Gene Polymorphisms with Autoimmune Thyroid Disease Risk and Clinical Features in the Iranian Population.

BACKGROUND: Grave's disease (GD) and Hashimoto's thyroiditis (HT) are autoimmune diseases of the thyroid gland in which genetic predisposition plays a major role in their development. Currently, the role of NLRP3 inflammasome and COX-2 has been documented in many autoimmune diseases. The purpose of the study is to delineate the impact of IL-1ß (rs1143634), NLRP3 (rs3806265), and COX-2 (rs2745557) gene polymorphisms in the development of GD and HT. METHODS: A total of 256 newly diagnosed patients with autoimmune thyroid disease (135 patients with HT and 121 GD patients) as case groups and 145 controls were included in the study. RESULTS: Recessive and overdominant models showed a significant association between IL-1ß rs1143634 SNP and HT development risk. The frequency of TT genotype and T allele of IL-1ß rs1143634 SNP in the control group was significantly higher than the GD group. There was no significant association between NLRP3 rs3806265 polymorphism and HT and GD development. The frequency of GA genotype of COX-2 (rs2745557) in the control group was significantly higher than that in the HT group. There was no significant association between COX-2 rs2745557 genotypic and allelic distribution and GD development risk. The results revealed a significant relationship between some clinical features of HT and GD groups and SNPs studied. CONCLUSION: The results manifest the significant impact of IL-1ß rs1143634 and COX-2 (rs2745557) SNPs and HT development and IL-1ß rs1143634 SNP on GD occurrence risk. Furthermore, a significant relationship was observed between some clinical features of HT and GD groups and studied SNPs.

The role of autophagy in controlling SARS-CoV-2 infection: An overview on virophagy-mediated molecular drug targets.

Autophagy-dependent cell death is a prominent mechanism that majorly contributes to homeostasis by maintaining the turnover of organelles under stressful conditions. Several viruses, including coronaviruses (CoVs), take advantage of cellular autophagy to facilitate their own replication. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a beta-coronavirus (ß-CoVs) that mediates its replication through a dependent or independent ATG5 pathway using specific double-membrane vesicles that can be considered as similar to autophagosomes. With due attention to several mutations in NSP6, a nonstructural protein with a positive regulatory effect on autophagosome formation, a potential correlation between SARS-CoV-2 pathogenesis mechanisms and autophagy can be expected. Certain medications, albeit limited in number, have been indicated to negatively regulate autophagy flux, potentially in a way similar to the inhibitory effect of ß-CoVs on the process of autophagy. However, there is no conclusive evidence to support their direct antagonizing effect on CoVs. Off-target accumulation of a major fraction of FDA-approved autophagy modulating drugs may result in adverse effects. Therefore, medications that have modulatory effects on autophagy could be considered as potential lead compounds for the development of new treatments against this virus. This review discusses the role of autophagy/virophagy in controlling SARS-CoV-2, focusing on the potential therapeutic implications.

Immunology, immunopathogenesis and immunotherapeutics of COVID-19; an overview.

Coronavirus disease 2019 (COVID-19) infection which is caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to a "public health emergency of international concern" (PHEIC). The infection is highly contagious, has a high mortality rate, and its pathophysiology remains poorly understood. Pulmonary inflammation with substantial lung damage together with generalized immune dysregulation are major components of COVID-19 pathogenesis. The former component, lung damage, seems to be at least in part a consequence of immune dysregulation. Indeed, studies have revealed that immune alteration is not merely an association, as it might occur in systemic infections, but, very likely, the core pathogenic element of COVID-19. In addition, precise management of immune response in COVID-19, i.e. enhancing anti-viral immunity while inhibiting systemic inflammation, may be key to successful treatment. Herein, we have reviewed current evidence related to different aspects of COVID-19 immunology, including innate and adaptive immune responses against the virus and mechanisms of virus-induced immune dysregulation. Considering that current antiviral therapies are chiefly experimental, strategies to do immunotherapy for the management of disease have also been reviewed. Understanding immunology of COVID-19 is important in developing effective therapies as well as diagnostic, and prophylactic strategies for this disease.

Comparison of clinical, para-clinical and laboratory findings in survived and deceased patients with COVID-19: diagnostic role of inflammatory indications in determining the severity of illness.

BACKGROUND: Since December 2019, when a cluster of pneumonia cases due to SARS-CoV-2 initially emerged in Wuhan city and then rapidly spread throughout the world, the necessity for data concerning the clinical and para-clinical features of Iranian patients with COVID-19 was highlighted. Therefore, we aimed to compare the clinical, para-clinical and laboratory evidences of deceased patients with survival group. METHODS: We extracted data regarding 233 patients with laboratory-confirmed COVID-19 from Buali Hospital in Iran; clinical/para-clinical and inflammatory indexes data were collected and analyzed. The data of laboratory examinations and chest CT findings were compared between deceased and survived patients. RESULTS: The mean age of the patients was 49.8 years and 64% of our patients were male. The acute respiratory distress syndrome occurred in 64 patients, 52 who were admitted to the ICU, which all of them underwent invasive mechanical ventilation, and 28 who died. Lymphopenia (79%), neutrophilia (79%), and thrombocytopenia (21%) were the most frequently observed laboratory findings of the deceased group on admission. Most patients (68%) had a high systematic immune-inflammation (SII) index of > 500 and increased C-reactive protein level (88%). Levels of inflammatory indexes such as neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and SII were documented to be significantly elevated in the deceased group when compared with the patients who survived (P < 0.0001, P < 0.001, P < 0.0001, respectively). The most commonly presented symptoms were fever (70%) and cough (63%) on admission. Headache was uncommon (11%). Ground-glass opacity with consolidation (mixed) was the most common radiologic finding on chest CT (51%). No radiographic or CT abnormality was found in 15 of 204 patients (7%). CONCLUSION: Small fraction of patients with COVID-19 may present without fever and abnormal radiologic findings. Elevated NLR, PLR and SII can be considered as prognostic and risk stratifying factor of severe form of disease.

Cytokines and COVID-19: friends or foes?

The cytokine storm following sepsis has been proven to be an important mechanism for triggering acute respiratory distress syndrome, which is a fatal uncontrolled systemic inflammation characterized by high concentrations of pro-inflammatory cytokines and chemokines, secreted by immune effector cells. The cytokine storm also occurs in the recently emerged novel coronavirus disease (COVID-19). Therefore, cytokines which usually help the immune system to fight infections are potentially harmful in the course of COVID-19 infections. Therefore, avoiding or mitigating the cytokine storm may be a key treatment for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

Immune responses and pathogenesis of SARS-CoV-2 during an outbreak in Iran: Comparison with SARS and MERS.

The beginning of 2020 has seen the emergence of COVID-19, an outbreak caused by a novel coronavirus, SARS-CoV-2, an important pathogen for humans. There is an urgent need to better understand this new virus and to develop ways to control its spread. In Iran, the first case of the COVID-19 was reported after spread from China and other countries. Fever, cough, and fatigue were the most common symptoms of this virus. In worldwide, the incubation period of COVID-19 was 3 to 7 days and approximately 80% of infections are mild or asymptomatic, 15% are severe, requiring oxygen, and 5% are critical infections, requiring ventilation. To mount an antiviral response, the innate immune system recognizes molecular structures that are produced by the invasion of the virus. COVID-19 infection induces IgG antibodies against N protein that can be detected by serum as early as day 4 after the onset of disease and with most patients seroconverting by day 14. Laboratory evidence of clinical patients showed that a specific T-cell response against SARS-CoV-2 is important for the recognition and killing of infected cells, particularly in the lungs of infected individuals. At present, there is no specific antiviral therapy for COVID-19 and the main treatments are supportive. In this review, we investigated the innate and acquired immune responses in patients who recovered from COVID-19, which could inform the design of prophylactic vaccines and immunotherapy for the future.

Association between COX-2 and 15-PGDH polymorphisms and SLE susceptibility.

AIMS: Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease. Prostaglandins E2 (PGE2), the product of the cyclo-oxygenase 2 (COX-2) enzyme, has critical roles in the etiology of autoimmune diseases. PGE2 level is controlled by a balance between its synthesis mediator (COX-2 enzyme) and its catabolic key enzyme (15-hydroxyprostaglandin dehydrogenase [15-PGDH] enzyme). In the present study, the associations of genotypic polymorphisms in COX-2 and 15-PGDH with SLE were investigated. METHODS: One hundred and sixty SLE patients and 160 healthy controls participated in the study. The polymerase chain reaction - restriction fragments length polymorphism method was used for genotyping. The COX-2 rs2745557 G/A and 15-PGDH rs8752 G/A polymorphisms were investigated. RESULTS: Regarding the COX-2 rs2745557 single nucleotide polymorphism, there was no significant association between COX-2 rs2745557 polymorphism and SLE. However, the dominant models showed a marginally significant relation (P = .048, odds ratio = 0.63, 95% CI = 0.4-1.0). Regarding GA genotype of 15-PGDH rd8752 polymorphism, there was a significant difference between two groups with a 4.5-fold increase in SLE development (P = .0001). The frequency of the A allele was higher in SLE patients than that in controls, showing a 1.4-fold increase in SLE development (P = .018). CONCLUSION: All results showed the protective effects of the dominant model of COX-2 rs2745557 polymorphism and risk factor of 15-PGDH rs8752 polymorphism on SLE development.

Obstetrics and Neonatal Outcomes in Pregnant Women with COVID-19: A Systematic Review.

BACKGROUND: Considering that the obstetricians and pediatricians need to comprehensive information about the obstetric and neonatal effect of COVID-19, this review study was conducted to investigate the impact of COVID-19 on obstetrics and neonatal outcomes. METHODS: In this systematic review the international search databases following PubMed, Web of Science, Scopus, ProQuest and Embase and Google scholar were searched. All articles were reviewed by two independent researchers until 10 April 2020. After quality assessment of included studies the finding reported in 2 sections obstetrics and neonatal outcomes. RESULTS: The sixteen studies with a sample size of 123 pregnant women with a definitive diagnosis of COVID-19 and their neonates were evaluated. The range of gestational age was 25-40 weeks. There was no death associated with COVID-19 in pregnant women. The obstetric outcomes in pregnant women with COVID-19 include decreased fetal movement, intrauterine fetal distress, anemia, PROM, preterm labor, Multiple Organ Dysfunction Syndrome (MODS) and etc. The most common delivery mode in women affect with COVID-19 was cesarean section. Expect for one case with MODS, in the majority of the studies reviewed, no severe morbidity or mortality occurred. The neonatal outcomes were stillbirth, prematurity, asphyxia, fetal distress, low birth weight, small for gestational age, large for gestational age, multiple organ dysfunction syndrome, disseminated intravascular coagulation and neonatal death. In addition, five neonates born to mothers with COVID-19 were positive for SARS-CoV-2. However, the studies report these outcomes but the exact causes of theme are not known. CONCLUSION: In this systematic review, we summarize the diverse results of studies about the obstetrics and neonatal outcomes following COVID-19. This infection may cause negative outcomes in both mothers and neonates. However, there were evidence about neonate infected with COVID-19, but there is controversial information about the vertical transmission of COVID-19.

The evaluation of VEGF and HIF-1α gene polymorphisms and multiple sclerosis susceptibility.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease that leads to myelin sheath destruction. Hypoxia-inducible factor 1 (HIF-1) has several roles in cells, such as inducing inflammation and angiogenesis. Recently, several lines of evidence have indicated the role of the hypoxia response and the HIF-1 signaling pathway in an autoimmune disease such as MS. The present study aimed to evaluate the effects of HIF-1α gene polymorphisms and vascular endothelial growth factor (VEGF) (as a major target gene of HIF-1α) gene polymorphism on MS susceptibility. METHODS: In total, 150 MS patients and 150 healthy age- and gender-matched people as a control group participated in the present study. The polymerase chain reaction-restriction fragment length polymorphism method was used for genotyping. RESULTS: The results obtained showed that the CC genotype of the VEGF rs699947 polymorphism was significantly higher in the case group than in the control group (p = 0.004). Also, we showed a significant relationship between the VEGF rs699947 polymorphism and MS in a dominant inheritance model (p = 0.005). Regarding the VEGF rs699947 polymorphism allelic distribution, the C allele frequency was significantly higher in the control group than in the case group (71.3% versus 61%, respectively, p = 0.009) and decreased the MS susceptibility by 1.6-fold (odds ratio = 1.6, 95% confidence interval = 1.2-2.2). There was no significant difference between the two groups with respect to HIF-1α rs11549465 genotypic distribution. The HIF-1α C111A polymorphism was non-polymorphic in our study population, except in the case group where nine subjects carried the CA genotype. CONCLUSIONS: We show a significant association between VEGF rs60047 polymorphism and MS susceptibility. However, our results do not show a significant association between MS and HIF-1α polymorphisms.

Simultaneous localization of multiple tumors from thermogram of tissue phantom by using a novel optimization algorithm inspired by hunting dogs.

The objective of this study is to couple the contact thermography method with a novel optimization algorithm to rapidly detect and localize the soft tissue tumor. To this end, experiments are carried out on tissue-mimicking phantoms containing resistance heaters to simulate the embedded tumors. An examiner robot is used to measure the temperature of the tissue surface. The time required for the examination of the tissue surface is reduced by developing a novel optimization algorithm called the Hunter Algorithm (HA). In the HA, population individuals are called the hunters, and the global maximum is referred to as the prey. The maximum temperature occurs at the location of the tumor. By the end of the hunting procedure, a flock of hunters converges to the maximum temperature and reaches the tumor while the examination time is significantly reduced. Performance of the HA is evaluated by applying the Genetic Algorithm (GA) and the Particle Swarm Optimization (PSO) algorithm to 11 test functions as minimization problems. It is observed that for the Ackley's function, as an example, the HA finds the global minimum after the 10th iteration with an accuracy of 10-4, while the PSO converges with the same accuracy after the 30th iteration and the accuracy of the GA remains about 0.002. In addition, the results show that the contact thermography in conjunction with the HA is of clinical importance in accurate detection of multiple tumors and small and deeply located tumors with insignificant thermal effects on the tissue surface.

Association between miRNA-152 polymorphism and risk of preeclampsia susceptibility.

BACKGROUND: Preeclampsia (PE) is one of the main causes of death among the pregnant women as well as newborns. Although the etiological cause of preeclampsia is not yet clear, a range of risk factors has been suggested. MicroRNAs (like miRNA-152) are small non-coding molecules that play a role in a wide spectrum of biological processes, such as cell proliferation and angiogenesis. This study aimed to investigate the possible relationship of miRNA-152 rs12940701 polymorphism and the risk of preeclampsia among the pregnant women as compared with the control group. METHODS: Genotyping of miRNA-152 rs12940701 polymorphism was performed using blood and placenta samples of 223 preeclampsia women and 229 normotensive pregnant women by a polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: The results obtained from maternal blood showed an increase in T alleles for PE women, that there was no significant difference between the PE and control group (OR = 1.7, P = 0.19). In addition, no significant difference was found in the TT genotype between the two groups (11.6% vs. 7%, OR = 1.4, P = 0.3). Similarly, the results obtained from placental samples were identical. CONCLUSIONS: A lack of relationship between the polymorphism of miRNA-152 rs12940701 gene and preeclampsia development has been shown.

Natural killer cell-based immunotherapy: From transplantation toward targeting cancer stem cells.

Natural killer (NK) cells are key players of the innate immune system. NK cells provide protection against infectious pathogens and malignancies in cell. This characteristic may be attributable to their intrinsic diverse potentialities and also their cooperation with adaptive immune lymphocytes, known as B and T cells. The growth, recurrence, and metastasis of cancer cells, and the failure of cytoreductive therapies against cancer cells are due to the small population of intratumor stem-like cells, called cancer stem cells (CSCs). Furthermore, NK cells can efficiently eradicate heterogeneous tumor cells after a long-term treatment. Therefore, NK cell-based therapy is a promising strategy to target and break CSC-associated resistance to anticancer drugs treatment. In this review, we have presented an overview of the emerging knowledge of the characteristics, diversities, and mechanism-driven immune surveillance of human NK cells and advances in NK cell-based immunotherapies. Finally, we will discuss how these cells can be applied to introduce the next generation of vaccine- and immune-based approaches to prevent drug resistance.