Methylation Status of miR-34a and miR-126 in Non-Small Cell Lung Cancer (NSCLC) Tumor Tissues.

Background: MiR-34a and miR-126 mainly act as tumor suppressors and are often downregulated in various cancers, including non-small cell lung cancer (NSCLC). We aimed to determine the methylation status of miR-34a and miR-126 in NSCLC patients. Methods: The current study included 63 paraffin-embedded NSCLC and paired adjacent normal tissues. After DNA extraction and bisulfite treatment, the methylation status of miR-34a and miR-126 were evaluated using the MSP method. Results: There was no statistically significant difference between tumor and normal tissues regarding the methylation status of miR-34a and miR-126 (p > 0.05). Moreover, we found no significant correlation between the methylation status of miR-34a and miR-126 with patients' demographic parameters, including gender, age, and pathology subtype (p > 0.05). Conclusion: Considering the low expression of mir-126 and mir-34 in NSCLC, more sensitive methods are recommended to be exploited for detecting the level of methylation or underlying mechanisms other than promoter hypermethylation in silencing these genes in NSCLC.

Tuberculosis and lung cancer: metabolic pathways play a key role.

Despite the fact that some cases of tuberculosis (TB) are undiagnosed and untreated, it remains a serious global public health issue. In the diagnosis, treatment, and control of latent and active TB, there may be a lack of effectiveness. An understanding of metabolic pathways can be fundamental to treat latent TB infection and active TB disease. Rather than targeting Mycobacterium tuberculosis, the control strategies aim to strengthen host responses to infection and reduce chronic inflammation by effectively enhancing host resistance to infection. The pathogenesis and progression of TB are linked to several metabolites and metabolic pathways, and they are potential targets for host-directed therapies. Additionally, metabolic pathways can contribute to the progression of lung cancer in patients with latent or active TB. A comprehensive metabolic pathway analysis is conducted to highlight lung cancer development in latent and active TB. The current study aimed to emphasize the association between metabolic pathways of tumor development in patients with latent and active TB. Health control programs around the world are compromised by TB and lung cancer due to their special epidemiological and clinical characteristics. Therefore, presenting the importance of lung cancer progression through metabolic pathways occurring upon TB infection can open new doors to improving control of TB infection and active TB disease while stressing that further evaluations are required to uncover this correlation.

Interferon-Induced Transmembrane Protein 3 rs34481144 C/T Genotype and Clinical Parameters Related to Progression of COVID-19.

Recent research has associated the interferon-induced transmembrane protein 3 gene (IFITM3) with the outcomes of coronavirus disease 2019 (COVID-19), although the findings are contradictory. This study aimed to determine the relationship between IFITM3 gene rs34481144 polymorphism and clinical parameters with COVID-19 mortality. The tetra-primer amplification refractory mutation system-polymerase chain reaction assay was used to analyze IFITM3 rs34481144 polymorphism in 1,149 deceased and 1,342 recovered patients. The clinical parameters were extracted from the patients' medical records. In this study, the frequency of IFITM3 rs34481144 CT genotypes (OR 1.47, 95% CI 1.23-1.76, P < 0.0001) in both sexes was significantly higher in deceased patients than in recovered patients. Moreover, IFITM3 rs34481144 TT genotypes (OR 3.38, 95% CI 1.05-10.87, P < 0.0001) in women were significantly associated with COVID-19 mortality. The multivariable logistic regression model results indicated that mean age (P < 0.001), alkaline phosphatase (P = 0.005), alanine aminotransferase (P < 0.001), low-density lipoprotein (P < 0.001), high-density lipoprotein (P < 0.001), fasting blood glucose (P = 0.010), creatinine (P < 0.001), uric acid (P < 0.001), C-reactive protein (P = 0.004), 25-hydroxyvitamin D (P < 0.001), erythrocyte sedimentation rate (P < 0.001), and real-time PCR Ct values (P < 0.001) were linked with increased COVID-19 death rates. In conclusion, IFITM3 rs34481144 gene polymorphism was linked to the mortality of COVID-19, with the rs34481144-T allele being especially important for mortality. Further studies are needed to confirm the results of this study.

rs12329760 Polymorphism in Transmembrane Serine Protease 2 Gene and Risk of Coronavirus Disease 2019 Mortality.

The protease produced by the transmembrane serine protease 2 (TMPRSS2) gene enhances viral infections and has been linked to severe acute respiratory syndrome coronavirus 2 pathogenesis. Therefore, this study evaluated the association between TMPRSS2 and coronavirus disease 2019 (COVID-19) mortality. TMPRSS2 rs12329760 polymorphism was genotyped using the tetraprimer amplification refractory mutation system-polymerase chain reaction method in 592 dead and 693 improved patients. In the current study, the frequency of TMPRSS2 rs12329760 CC than TT genotypes was significantly lower in improved patients than in dead patients. According to the findings of the multivariate logistic regression test, higher levels of mean age, creatinine, erythrocyte sedimentation rate, C-reactive protein, aspartate aminotransferase, lower levels of 25-hydroxyvitamin D, uric acid, and real-time PCR Ct values and TMPRSS2 rs12329760 CC genotype were observed to be associated with increased COVID-19 mortality rates. In conclusion, the TMPRSS2 rs12329760 CC genotype was a polymorphism linked to a significantly higher incidence of severe COVID-19. Further studies are required to corroborate the obtained findings.

Increased risk of COVID-19 mortality rate in IFITM3 rs6598045 G allele carriers infected by SARS-CoV-2 delta variant.

BACKGROUND: The interferon-induced transmembrane-protein 3 (IFITM3) is a vital component of the immune system's defense against viral infection. Variants in the IFITM3 gene have been linked to changes in expression and the risk of severe Coronavirus disease 2019 (COVID-19). This study aimed to investigate whether IFITM3 rs6598045, quantitative polymerase chain reaction (qPCR) cycle threshold (Ct) values, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are associated with an increased mortality rate of COVID-19. METHODS: The genotyping of IFITM3 rs6598045 polymorphism was analyzed using the amplification refractory mutation system-polymerase chain reaction in 1342 recovered and 1149 deceased patients positive for SARS-CoV-2. RESULTS: In this study, IFITM3 rs6598045 G allele as minor allele frequency was significantly more common in the deceased patients than in the recovered ones. Furthermore, the highest mortality rates were observed in Delta variant and lowest qPCR Ct values. COVID-19 mortality was associated with IFITM3 rs6598045 GG and AG in Delta variant and IFITM3 rs6598045 AG in Alpha variant. A statistically significant difference was observed in the qPCR Ct values between individuals with GG and AG genotypes and those with an AA genotype. CONCLUSION: A possible correlation was observed between the mortality rate of COVID-19, the G allele of IFITM3 rs6598045, and SARS-CoV-2 variants. However, large-scale research is still required to validate our results.

ABO rs657152 and Blood Groups Are as Predictor Factors of COVID-19 Mortality in the Iranian Population.

Several studies have discovered a relationship between specific blood types, genetic variations of the ABO gene, and coronavirus disease 2019 (COVID-19). Therefore, the aim of this study was to evaluate the association between ABO rs657152 polymorphisms and ABO blood groups with COVID-19 mortality. The tetraprimer amplification refractory mutation system, polymerase chain reaction method, was used for ABO rs657152 polymorphism genotyping in 1,211 dead and 1,442 improved patients. In the current study, the frequency of ABO rs657152 AA than CC genotypes was significantly higher in dead patients than in improved patients. Our findings indicated that blood type A was associated with the highest risk of COVID-19 mortality compared to other blood groups, and patients with blood type O have a lower risk of infection, suggesting that blood type O may be a protective factor against COVID-19 mortality. Multivariate logistic regression test indicated that higher COVID-19 mortality rates were linked with alkaline phosphatase, alanine aminotransferase, high density lipoprotein, low-density lipoprotein, fasting blood glucose, uric acid, creatinine, erythrocyte sedimentation rate, C-reactive protein, 25-hydroxyvitamin D, real-time PCR Ct values, ABO blood groups, and ABO rs657152 AA genotype. In conclusion, the AA genotype of ABO rs657152 and blood type A were associated with a considerably increased frequency of COVID-19 mortality. Further research is necessary to validate the obtained results.

The role of ACE1 I/D and ACE2 polymorphism in the outcome of Iranian COVID-19 patients: A case-control study.

Background: Since the beginning of the pandemic of coronavirus disease 2019 (COVID-19), many countries have experienced a considerable number of COVID-19 cases and deaths. The etiology of a broad spectrum of symptoms is still debated. Host genetic variants might also significantly influence the outcome of the disease. This study aimed to evaluate the association of angiotensin-converting enzyme (ACE1) gene Insertion/Deletion (I/D) polymorphism (rs1799752) and ACE2 gene rs1978124 single nucleotide polymorphism with the COVID-19 severity. Methods: This study was conducted on 470 COVID-19 patients and a control group of 56 healthy individuals across several major cities in Iran. The blood sample and clinical data were collected from the participants, and their ACE1 I/D and ACE2 rs1978124 polymorphisms were determined using polymerase chain reaction and PCR-RFLP, respectively. Serum levels of C-reactive protein (CRP), interleukin 6 (IL-6), and ACE1 were measured in the blood samples. Results: We found that the ACE1 DD genotype frequency was inversely correlated with the risk of intubation (p = 0.017) and mortality in COVID-19 patients (p = 0.049). Even after adjustment, logistic regression demonstrated that this significant inverse association remained constant for the above variables at odds ratios of (OR) = 0.35 and Odds Ratio = 0.49, respectively. Also, in the expired (p = 0.042) and intubated (p = 0.048) groups with II + ID genotypes, the mean level of CRP was significantly higher than in the DD genotype group. Furthermore, in both intubated and expired groups, the mean serum level of ACE1 was higher compared with non-intubated and survived groups with II or II + ID genotypes. The results also indicated that ACE2 rs1978124 TT + CT genotypes in females have a significant positive role in susceptibility to COVID-19; however, in females, the TT + CT genotypes had a protective effect (OR = 0.098) against the severity of COVID-19. Conclusion: These findings suggest that ACE1 I/D and ACE2 rs1978124 polymorphism could potentially influence the outcome of COVID-19 in the Iranian population.

Angiotensin-converting enzyme 2 rs2285666 polymorphism and clinical parameters as the determinants of COVID-19 severity in Iranian population.

Host genetic factors may be correlated with the severity of coronavirus disease 2019 (COVID-19). Angiotensin-converting enzyme 2 (ACE2) plays a vital role in viral cell entrance. The current study aimed to evaluate the association of ACE2 rs2285666 polymorphism and clinical parameters with COVID-19 mortality. The ACE2 rs2285666 polymorphism was genotyped using the polymerase chain reaction-restriction fragment length polymorphism in 556 recovered and 522 dead patients. In this study, the frequency of ACE2 rs2285666 CC was significantly higher than TT genotype in dead patients. The multivariate logistic regression analysis results showed that the higher levels of alanine aminotransferase, alkaline phosphatase, creatinine, erythrocyte sedimentation rate, and C-reactive protein and the low levels of uric acid, cholesterol, low density lipoprotein, 25-hydroxyvitamin D, real-time PCR Ct values, and ACE2 rs2285666 CC genotype were associated with increased mortality rates after COVID-19. In conclusion, our findings demonstrated a possible link between COVID-19 mortality, clinical parameters, and ACE2 rs2285666 CC. Further research is required to confirm these results.

Impact of interferon-induced transmembrane protein 3 gene rs12252 polymorphism on COVID-19 mortality.

BACKGROUND AND AIMS: Interferon-induced transmembrane protein 3 (IFITM3) plays a critical role in the adaptive and innate immune response by preventing membrane hemifusion between the host and viral cell cytoplasm. This study aimed to evaluate whether IFITM3 rs12252 polymorphism is related to an increased mortality rate of coronavirus disease 2019 (COVID-19). METHODS: The IFITM3 rs12252 polymorphism was genotyped using the amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) in 548 dead and 630 improved patients positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). RESULTS: In the present study, the minor allele frequency of IFITM3 rs12252 (C) was significantly more frequent in dead patients than in improved cases. The results of the multivariate logistic regression analysis indicated that the lower lipid profiles, PCR Ct value, 25-hydroxyvitamin D, and uric acid and higher levels of erythrocyte sedimentation rate (ESR), liver enzymes, and creatinine, and IFITM3 rs12252 CC genotypes were related to the COVID-19 infection mortality. CONCLUSIONS: In summary, our findings suggested a possible link between the mortality of COVID-19 infection, the CC genotypes of IFITM3 rs12252, and clinical parameters. Further investigations are required worldwide to prove the link relationship of COVID-19 mortality with host genetic factors.

Commensal and Pathogenic Bacterial-Derived Extracellular Vesicles in Host-Bacterial and Interbacterial Dialogues: Two Sides of the Same Coin.

Extracellular vesicles (EVs) cause effective changes in various domains of life. These bioactive structures are essential to the bidirectional organ communication. Recently, increasing research attention has been paid to EVs derived from commensal and pathogenic bacteria in their potential role to affect human disease risk for cancers and a variety of metabolic, gastrointestinal, psychiatric, and mental disorders. The present review presents an overview of both the protective and harmful roles of commensal and pathogenic bacteria-derived EVs in host-bacterial and interbacterial interactions. Bacterial EVs could impact upon human health by regulating microbiota-host crosstalk intestinal homeostasis, even in distal organs. The importance of vesicles derived from bacteria has been also evaluated regarding epigenetic modifications and applications. Generally, the evaluation of bacterial EVs is important towards finding efficient strategies for the prevention and treatment of various human diseases and maintaining metabolic homeostasis.

RNA Expression Analysis of Mycobacterial Methyltransferases Genes in Different Resistant Strains of Mycobacterium tuberculosis.

Background: Tuberculosis infection still represents a global health issue affecting patients worldwide. Strategies for its control may be not as effective as it should be, specifically in case of resistant strains of Mycobacterium tuberculosis (M.tb.) In this regard, the role of mycobacterial methyltransferases (MTases) in TB infection can be fundamental, though it has not been broadly deciphered. Methods: Five resistant isolates of M.tb were obtained. M.tb H37Rv (ATCC 27249) was used as a reference strain. Seven putative mycobacterial MTase genes (Rv0645c, Rv2966c, Rv1988, Rv1694, Rv3919c, Rv2756c, and Rv3263) and Rv1392 as SAM synthase were selected for analysis. PCR-sequencing and qRT-PCR were performed to compare mutations and expression levels of MTases in different strains. The 2-ΔΔCt method was employed to calculate the relative expression levels of these genes. Results: Only two mutations were found in isoniazid resistance (INHR) strain for Rv3919c (T to G in codon 341) and Rv1392 (G to A in codon 97) genes. Overexpression of Rv0645c, Rv2756c, Rv3263, and Rv2966c was detected in all sensitive and resistant isolates. However, Rv1988 and Rv3919c decreased and Rv1694 increased in the sensitive strains. The Rv1392 expression level also decreased in INHR isolate. Conclusion: We found a correlation between mycobacterial MTases expression and resistance to antibiotics in M.tb strains. Some MTases undeniably are virulence factors that specifically hijack the host defense mechanism. Further evaluations are needed to explore the complete impact of mycobacterial MTases within specific strains of M.tb to introduce novel diagnosis and treatment strategies.

Interpretation of Hematological, Biochemical, and Immunological Findings of COVID-19 Disease: Biomarkers Associated with Severity and Mortality.

The severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) spread rapidly all over the world in late 2019 and caused critical illness and death in some infected patients. This study aimed at examining several laboratory factors, especially inflammatory and immunological mediators, to identify severity and mortality associated biomarkers. Ninety-three hospitalized patients with confirmed coronavirus disease 2019 (COVID-19) were classified based on disease severity. The levels of biochemical, hematological, immunological, and inflammatory mediators were assessed, and their association with severity and mortality were evaluated. Hospitalized patients were mostly men (77.4%) with an average (standard deviation) age of 59.14 (14.81) years. The mortality rate was significantly higher in critical patients (85.7%). Increased serum levels of blood sugar, urea, creatinine, uric acid, phosphorus, total bilirubin, serum glutamic-oxaloacetic transaminase, serum glutamic-oxaloacetic transaminase, lactic dehydrogenase, C-reactive protein, ferritin, and procalcitonin were significantly prevalent (p=0.002, p<0.001, p<0.001, p=0.014, p=0.047, p=0.003, p<0.001, p<0.001, p<0.001, p<0.001, P<0.001, and p<0.001, respectively) in COVID-19 patients. Decreased red blood cell, hemoglobin, and hematocrit were significantly prevalent among COVID-19 patients than healthy control subjects (p<0.001 for all). Troponin-I, interleukin-6, neutrophil/lymphocyte ratio (NLR), procalcitonin, and D-dimer showed a significant association with the mortality of patients with specificity and sensitivity more than 60%. Age, sex, underlying diseases, blood oxygen pressure, complete blood count along with C-reactive protein, lactic dehydrogenase, procalcitonin, D-dimer, and interleukin-6 evaluation help to predict the severity and required management for COVID-19 patients. Further investigations are highly recommended in a larger cohort study for validation of the present findings.

Evaluation of Merkel cell polyomavirus in non-small cell lung cancer and adjacent normal cells.

Several risk factors have been linked to lung cancer (LC). Nevertheless, a viral etiology has been mentioned for a subset of patients developing LC. The aim of this study was to evaluate the effect of Merkel cell polyomavirus (MCPyV) on developing non-small cell lung cancer (NSCLCs). In total, 96 paraffin-embedded NSCLC biopsies and 96 adjacent non-LC normal specimens were analyzed by quantitative real-time polymerase chain reaction (PCR) for the existence of the MCPyV DNA and the expressions of RNA transcripts. Among the 96 enrolled participants, 42 patients were adenocarcinomas (ADs) and 54 patients were squamous cell carcinoma (SCC). Of the 42 ADs, MCPyV DNA was determined in 15 (35.7%) samples and of the 54 SCC, MCPyV DNA was detected in 22 (40.7%) samples. Only one non-cancerous sample in SCC subjects was positive for MCPyV LT-Ag DNA load (0.216 × 10-3). In MCPyV-positive subjects, the median MCPyV copy number was higher in the patients with ADs (0.016 × 10-3 copies/cell) compared to SCCs (0.005 × 10-3 copies/cell); but this difference was not statistically significant (P = 0.913). In the seven stages of LC, the MCPyV LT-Ag was quantified in stage IV (0.204 × 10-3 copies/cell) more than in other stages. There was statistically significant difference between stages of cancer and MCPyV LT-Ag DNA load (P = 0.002). These results revealed for the first time the presence of MCPyV in a subset of patients with NSCLCs in Iran. Further studies should be carried out to clarify the role of MCPyV in lung carcinogenesis.