Epigenetic modulation of cytokine expression in Mycobacterium tuberculosis-infected monocyte derived-dendritic cells: Implications for tuberculosis diagnosis.

BACKGROUND: To delineate alterations in DNA methylation at high resolution within the genomic profile of monocyte-derived-dendritic cells (mo-DCs) in connection with Mycobacterium tuberculosis (MTB) infection, with particular emphasis on pro/ anti-inflammatory genes. METHODS: In the context of this investigation, mo-DCs were infected by various active strains of MTB (Rifampicin-resistant [RIFR], H37Rv, multidrug-resistant [MDR], and extensively drug-resistant [XDR]). Subsequently, the pro/anti-inflammatory hub gene expression levels within the IL-6, IL-12, IFN-γ, IL-1ß, TNF-α, and IL-10 pathways were evaluated employing real-time reverse transcription-polymerase chain reaction (RT-PCR). Additionally, the effects of MTB infection on mo-DC protein expression were examined through western blot analysis. The methylation status (%) of TNF-α and IL-10 was considered through Methylation Sensitive-High Resolution Melting (MS-HRM). RESULTS: The results revealed an up-regulation of all pro-inflammatory genes among all groups, with TNF-α exhibiting the highest expression level. Conversely, the anti-inflammatory gene (IL-10) showed a down-regulated expression level. Furthermore, the DNA methylation status (%) of TNF-α decreased significantly among all the groups (P < 0.001), although there were no notable distinctions in the DNA methylation status (%) of IL-10 when compared to the control group (P > 0.05). CONCLUSION: MTB infection induces DNA methylation changes in mo-DCs. The hypo-methylation of TNF-α may induce the up-regulation of this gene. This correlation revealed that the more resistant the MTB strain (XDR) is, the lower the methylation status (%) in the TNF-α gene.

Association between interleukin-10 gene polymorphisms (rs1800871, rs1800872, and rs1800896) and severity of infection in different SARS-CoV-2 variants.

BACKGROUND: Polymorphisms in the interleukin-10 (IL10) gene have been linked to the severity of the patients infected with the viral infections. This study aimed to assess if the IL10 gene polymorphisms rs1800871, rs1800872, and rs1800896 were linked to coronavirus disease 19 (COVID-19) mortality in different severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in the Iranian population. METHODS: For genotyping IL10 rs1800871, rs1800872, and rs1800896, this study used the polymerase chain reaction-restriction fragment length polymorphism method in 1,734 recovered and 1,450 deceased patients. RESULTS: The obtained finding indicated IL10 rs1800871 CC genotype in the Alpha variant and CT genotype in the Delta variant had a relationship with COVID-19 mortality; however, there was no association between rs1800871 polymorphism and the Omicron BA.5 variant. The COVID-19 mortality rate was associated with IL10 rs1800872 TT genotype in the Alpha and Omicron BA.5 variants and GT in the Alpha and Delta variants. The COVID-19 mortality rate was associated with IL10 rs1800896 GG and AG genotypes in the Delta and Omicron BA.5; nevertheless, there was no association between rs1800896 polymorphism with the Alpha variant. According to the obtained data, the GTA haplotype was the most common of haplotype in different SARS-CoV-2 variants. The TCG haplotype was related to COVID-19 mortality in the Alpha, Delta and Omicron BA.5 variants. CONCLUSION: The IL10 polymorphisms had an impact on COVID-19 infection, and these polymorphisms had different effects in various SARS-CoV-2 variants. To verify the obtained results, further studies should be conducted on various ethnic groups.

The impact of ACE2 polymorphisms (rs1978124, rs2285666, and rs2074192) and ACE1 rs1799752 in the mortality rate of COVID-19 in different SARS-CoV-2 variants.

BACKGROUND: Clinical severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outcomes could be influenced by genetic polymorphisms in angiotensin I-converting enzyme (ACE1) and ACE2. This study aims to examine three polymorphisms (rs1978124, rs2285666, and rs2074192) on the ACE2 gene and ACE1 rs1799752 (I/D) in patients who have coronavirus disease 2019 (COVID-19) with various SARS-CoV-2 variants. METHODS: Based on polymerase chain reaction-based genotyping, four polymorphisms in the ACE1 and ACE2 genes have been identified in 2023 deceased patients and 2307 recovered patients. RESULTS: The ACE2 rs2074192 TT genotype was associated with the COVID-19 mortality in all three variants, whereas the CT genotype was associated with the Omicron BA.5 and Delta variants. ACE2 rs1978124 TC genotypes were related to COVID-19 mortality in the Omicron BA.5 and Alpha variants, but TT genotypes were related to COVID-19 mortality in the Delta variant. It was found that ACE2 rs2285666 CC genotypes were associated with COVID-19 mortality in Delta and Alpha variants, and CT genotypes in Delta variants. There was an association between ACE1 rs1799752 DD and ID genotypes in the Delta variant and COVID-19 mortality, whereas there was no association in the Alpha or Omicron BA.5 variants. In all variants of SARS-CoV-2, CDCT and TDCT haplotypes were more common. In Omicron BA.5 and Delta, CDCC and TDCC haplotypes were linked with COVID-19 mortality. In addition to COVID-19 mortality, the CICT, TICT, and TICC were significantly correlated. CONCLUSION: The ACE1/ACE2 polymorphisms had an impact on COVID-19 infection, and these polymorphisms had different effects in various SARS-CoV-2 variants. To confirm these results, however, more research needs to be conducted.

The importance of heteroresistance and efflux pumps in bedaquiline-resistant Mycobacterium tuberculosis isolates from Iran.

BACKGROUND: Tuberculosis (TB) continues to pose a threat to communities worldwide and remains a significant public health issue in several countries. We assessed the role of heteroresistance and efflux pumps in bedaquiline (BDQ)-resistant Mycobacterium tuberculosis isolates. METHODS: Nineteen clinical isolates were included in the study, of which fifteen isolates were classified as MDR or XDR, while four isolates were fully susceptible. To evaluate BDQ heteroresistance, the Microplate Alamar Blue Assay (MABA) method was employed. For screening mixed infections, MIRU-VNTR was performed on clinical isolates. Mutations in the atpE and Rv0678 genes were determined based on next-generation sequencing data. Additionally, real-time PCR was applied to assess the expression of efflux pump genes in the absence and presence of verapamil (VP). RESULTS: All 15 drug-resistant isolates displayed resistance to BDQ. Among the 19 total isolates, 21.05% (4/19) exhibited a heteroresistance pattern to BDQ. None of the isolates carried a mutation of the atpE and Rv0678 genes associated with BDQ resistance. Regarding the MIRU-VNTR analysis, most isolates (94.73%) showed the Beijing genotype. Fifteen (78.9%) isolates showed a significant reduction in BDQ MIC after VP treatment. The efflux pump genes of Rv0676c, Rv1258c, Rv1410c, Rv1634, Rv1819, Rv2459, Rv2846, and Rv3065 were overexpressed in the presence of BDQ. CONCLUSIONS: Our results clearly demonstrated the crucial role of heteroresistance and efflux pumps in BDQ resistance. Additionally, we established a direct link between the Rv0676c gene and BDQ resistance. The inclusion of VP significantly reduced the MIC of BDQ in both drug-susceptible and drug-resistant clinical isolates.

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.

On the relationship between tripartite motif-containing 22 single-nucleotide polymorphisms and COVID-19 infection severity.

BACKGROUND: The tripartite motif containing (TRIM)-22 participates in innate immune responses and exhibits antiviral activities. The present study aimed to assess of the relationship between TRIM22 single-nucleotide polymorphisms and clinical parameters with the coronavirus disease 2019 (COVID-19) infection severity. METHODS: TRIM22 polymorphisms (rs7113258, rs7935564, and rs1063303) were genotyped using TaqMan polymerase chain reaction (PCR) assay in 495 dead and 497 improved severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-positive patients. RESULTS: In this study, the frequencies of TRIM22 rs1063303 GG, rs7935564 GG, and rs7113258 TT were significantly higher in dead patients than in improved patients, and higher viral load with low PCR Ct value was noticed in dead patients. The multivariate logistic regression analysis revealed that the lower levels of low-density lipoprotein (LDL), cholesterol, PCR Ct value, and lower 25-hydroxyvitamin D, and also higher levels of erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and TRIM22 rs1063303 GG, rs7113258 TT, and rs3824949 GG genotypes were related to the COVID-19 infection severity. CONCLUSION: Our finding proved the probable relationship between the COVID-19 infection severity with the genotypes of TRIM22 SNPs and clinical parameters. More research is required worldwide to show the association between the COVID-19 infection severity and host genetic factors.

Relationship between CDX2 rs11568820 and EcoRV rs4516035 polymorphisms on the vitamin D receptor gene with susceptibility to different SARS-CoV-2 variants.

Several studies have revealed that vitamin D deficiency is linked to an increased risk of developing coronavirus disease 19 (COVID-19). In individuals with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, vitamin D receptor activation is required to decrease acute respiratory distress syndrome. The purpose of this study was to examine the genotypic distribution and allelic frequencies of CDX2 rs11568820 and EcoRV rs4516035 polymorphisms in COVID-19 patients with various SARS-CoV-2 variants. For genotyping of CDX2 rs11568820 and EcoRV rs4516035 polymorphisms, we used the polymerase chain reaction-restriction fragment length polymorphism technique in 1734 and 1450 recovered and deceased patients, respectively. The results indicated the rate of COVID-19 mortality was associated with CDX2 rs11568820 AA and GA genotypes in the Delta variant and with CDX2 rs11568820 AA in the Omicron BA.5 variant, while no association was shown in the Alpha variant. Therefore, the rate of COVID-19 mortality was associated with EcoRV rs4516035 TC and CC genotypes in the Delta variant, while no association was shown in the Alpha and Omicron BA.5 variants. According to our analysis, the T-G haplotype was more common in all SARS-CoV-2 variants. The C-A haplotype was associated with COVID-19 mortality in the Delta and Omicron BA.5 variants, and the T-A haplotype was related to the Alpha variant. In conclusion, the genotype frequencies of the CDX2 rs11568820 and EcoRV rs4516035 polymorphisms between SARS-CoV-2 variants were significantly different between the deceased patients and recovered patients. However, more studies should be done to confirm the results.

Tuberculosis prevention, diagnosis, and treatment financial profile during 2006-2021: PART A.

BACKGROUND: Tuberculosis (TB) is a communicable disease that is a major cause of death and one of the leading causes of death worldwide. Currently, there is no analyzed data to examine the financial profile of TB by country, continent, and year; this article analyzed TB prevention, diagnosis, and treatment financial profile during the last two decades. METHODS: Original research, reviews, and governmental databases are analyzed to present the financial profile of TB. RESULTS: Analyzed data showed Europe (23137.133), Asia (20137.073), and Africa (15237.973) had the most allocated funds (US $ million), and Oceania (236.702), and America (4745.043) had the lowest allocated fund (US $ million) during 2006-2021. Additionally, the allocation of funds (domestic funds, global funds, and grants [excluding global funds]) in different countries and proper planning for TB eradication has caused that in the last two decades, the slope of the confirmed cases and deaths graph line is negative. CONCLUSION: The number of confirmed cases and deaths reported globally is decreasing. The trend lines showed that the assigned funds are increasing, indicating that the TB eradication plan can be apprehended soon.

The impact of Akkermansia muciniphila and its extracellular vesicles in the regulation of serotonergic gene expression in a small intestine of mice.

OBJECTIVES: A better understanding of host-microbe interactions as a cross-talk between the gastrointestinal (GI) tract and the gut microbiota can help treat and prevent GI disorders by improving the maintenance of GI homeostasis. The gut microbiota can affect signaling molecules, such as serotonin, which regulates endocrine systems through the GI tract. Moreover, studying the effects of gut microbiota in the small intestine on the human GI tract health is pivotal. METHODS: Male C57BL/6J mice (n = 30, 10 mice per group) were orally gavaged with 200 µL of PBS (control group); mice in group II were orally gavaged with 109 colony-forming units (CFU)/200 µL of viable A. muciniphila, suspended in PBS (A. muciniphila group); and mice in group III were orally gavaged with 10 µg of protein/200 µL of EVs (A. muciniphila-EV group) once daily for four weeks. The gene expression of serotonin system-related genes (Slc6a4, Tph1, Mao, Htr3, Htr4, and Htr7) was examined by quantitative real-time PCR (qPCR) method. RESULTS: Based on the results, A. muciniphila significantly affected the mRNA expression of genes related to the serotonin system (Tph1, Mao, Htr3B, and Htr7) in the duodenum and (Htr3B, Htr4 and Htr7) in the ileum of mice (P < 0.05). Moreover, A. muciniphila-derived EVs affected the expression of major genes related to the serotonin system (Tph1, slc6a4a, Mao, Htr3B, Htr4, and Htr7) in the duodenum and ileum of mice (P < 0.05). CONCLUSIONS: The present findings may pave the way for further investigation of the effects of strain-specific probiotics on the serotonergic system, which is currently in its infancy.

Identification of a novel fully human anti-toxic shock syndrome toxin (TSST)-1 single-chain variable fragment antibody averting TSST-1-induced mitogenesis and cytokine secretion.

BACKGROUND: Staphylococcal superantigens are virulence factors that help the pathogen escape the immune system and develop an infection. Toxic shock syndrome toxin (TSST)-1 is one of the most studied superantigens whose role in toxic shock syndrome and some particular disorders have been demonstrated. Inhibiting TSST-1 production with antibiotics and targeting TSST-1 with monoclonal antibodies might be one of the best strategies to prevent TSST-1-induced cytokines storm followed by lethality. RESULTS: A novel single-chain variable fragment (scFv), MS473, against TSST-1 was identified by selecting an scFv phage library on the TSST-1 protein. The MS473 scFv showed high affinity and specificity for TSST-1. Moreover, MS473 could significantly prevent TSST-1-induced mitogenicity (the IC50 value: 1.5 µM) and cytokine production. CONCLUSION: Using traditional antibiotics with an anti-TSST-1 scFv as a safe and effective agent leads to deleting the infection source and preventing the detrimental effects of the toxin disseminated into the whole body.

Isolation of nontuberculous mycobacteria species from different water sources: a study of six hospitals in Tehran, Iran.

PURPOSE: Nontuberculous mycobacteria (NTM) are ubiquitous bacteria that are naturally resistant to disinfectants and antibiotics and can colonize systems for supplying drinking water. Therefore, this study aimed to evaluate the prevalence of NTM in the drinking water of six hospitals in Tehran, Iran. METHODS: Totally, 198 water samples were collected. Each water sample was filtered via a membrane filter with a pore size of 0.45 µm and then decontaminated by 0.005% cetylpyridinium chloride. The membrane filters were incubated on two Lowenstein-Jensen media at 25 °C and 37 °C for 8 weeks. The positive cultures were identified with phenotypic tests, and then NTM species were detected according to the hsp65, rpoB, and 16S rDNA genes. Drug susceptibility testing (DST) was also carried out. RESULTS: Overall, 76 (40.4%) of the isolates were slowly growing mycobacteria (SGM) and 112 (59.6%) of the ones were rapidly growing mycobacteria (RGM). The most common NTM were Mycobacterium aurum, M. gordonae, M. phocaicum, M. mucogenicum, M. kansasii, M. simiae, M. gadium, M. lentiflavum, M. fortuitum, and M. porcinum. Among these 188 samples, NTM ranged from 1 to > 300 colony-forming unit (CFU) /500 mL, with a median of 182 CFU/500 mL. In the infectious department of all hospitals, the amount of CFU was higher than in other parts of the hospitals. The DST findings in this study indicated the diversity of resistance to different drugs. Among RGM, M. mucogenicum was the most susceptible isolate; however, M. fortuitum showed a different resistance pattern. Also, among SGM isolates, M. kansasii and M. simiae, the diversity of DST indicated. CONCLUSIONS: The current study showed NTM strains could be an important component of hospital water supplies and a possible source of nosocomial infections according to the CFU reported in this study. The obtained findings also help clarify the dynamics of NTM variety and distribution in the water systems of hospitals in the research area.

BK polyomavirus in Iranian patients with papillary thyroid cancer: Is it a major future challenge?

BK polyomavirus (BKPyV) is a well-known cause of nephropathy in renal transplant recipients. It has recently received much attention from researchers as a major predisposing factor for various cancers. This study aimed to investigate how BKPyV affected the advancement of papillary thyroid carcinoma (PTC). A total of 1057 samples were tested for BKPyV DNA and RNA, comprising 645 paraffin-embedded PTC biopsy samples (PEBS), 412 fresh biopsy samples (FBS), and 1057 adjacent noncancerous samples. The BKPyV DNA was found in 511 (48.3%) of the specimens, including 347 (84.2%) FBS and 164 (25.4%) PEBS. The mean BKPyV copy number was significantly lower in patients with PEBS (0.5 × 10-4 ± 0.1 × 10-4 copies/cell) than in FBS (1.3 × 10-1 ± 0.2 × 10-1 copies/cell) and non-PTC normal samples (0.3 × 10-5 ± 0.04 × 10-5 copies/cell). The PEBS had lower LT-Ag RNA expression than FBS, and no VP1 gene transcript expression was detected. In conclusion, although our findings indicated the presence of BKPyV in some Iranian PTC patients, more research is needed to corroborate these findings.

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.

Traces of JC polyomavirus in papillary thyroid cancer: a comprehensive study in Iran.

BACKGROUND: JC polyomavirus (JCPyV) is known to induce solid tumors such as astrocytomas, glioblastomas, and neuroblastomas in experimental animals, and recent studies have shown that the virus may be correlated with carcinogenesis. This study aimed to evaluate the impact of JCPyV on the progression of papillary thyroid cancer (PTC). METHODS: A total of 1057 samples, including 645 paraffin-embedded PTC biopsy samples (PEBS) and 412 fresh biopsy samples (FBS), and 1057 adjacent non-cancerous samples were evaluated for the presence of JCPyV DNA and RNA. RESULTS: We observed that 10.8% (114/1057) samples, including 17.5% (72/412) FBS and 6.5% (42/645) PEBS were positive for the JCPyV DNA. Among the JCPyV-positive samples, the mean JCPyV copy number was lower in patients with PEBS (0.3 × 10-4 ± 0.1 × 10-4 copies/cell) compared to FBS (1.8 × 10-1 ± 0.4 × 10-1 copies/cell) and non-PTC normal samples (0.2 × 10-5 ± 0.01 × 10-5 copies/cell), with a statistically significant difference (P < 0.001). The LT-Ag RNA expression was lower in PEBS than in FBS, while no VP1 gene transcript expression was found. CONCLUSIONS: Although our results confirmed the presence of JCPyV in some Iranian patients with PTC, more research is needed to verify these results.

Comparing the expression levels of tripartite motif containing 28 in mild and severe COVID-19 infection.

BACKGROUND: Tripartite motif-containing 28 (TRIM28) is an impressive regulator of the epigenetic control of the antiviral immune response. This study evaluated if the differential expression of TRIM28 correlates with the severity of coronavirus disease 2019 (COVID-19) infection. METHODS: A total of 330 COVID-19 patients, including 188 mild and 142 severe infections, and 160 healthy controls were enrolled in this study. Quantitative real-time polymerase chain reaction (qPCR) was used to determine the expression levels of TRIM28 in the studied patients. RESULTS: TRIM28 mRNA levels were significantly lower in both groups of patients versus the control group and in the severe group indicated further reduction in comparison to mild infection. The multivariate logistic regression analysis showed the mean age, lower levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), cholesterol, lower 25-hydroxyvitamin D, and PCR cycle threshold (Ct) value and higher levels of erythrocyte sedimentation rate (ESR) and differential expression of TRIM28 were linked to the severity of COVID-19 infection. CONCLUSION: The results of this study proved that the downregulation of TRIM28 might be associated with the severity of COVID-19 infection. Further studies are required to determine the association between the COVID-19 infection severity and TRIM family proteins.

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.

Interaction between Clostridium species and microbiota to progress immune regulation.

Gut microbiota can interact with the immune system through direct or indirect pathways. In the indirect pathway, gut microbiota produces metabolites such as short chain fatty acids (SCFAs), which may modulate the immune response. SCFAs reduce inflammation, repair intestinal barrier, and induce propagation of specific immune cells, e.g., T regulatory cells (Treg), which can suppress reactive cells such as macrophage and dendritic cells (DCs). As one of the most dominant members of microbiota, Clostridium produces SCFAs. As one of SCFA members, butyrate plays an important role in the modulation of immune cells. Through butyrate production, Clostridium helps to generate aryl hydrocarbon receptor (AhR). AhR interacts with many proteins inside the cytoplasm including Heat Shock Protein 90 (HSP 90), HSP 23, and chaperone. Activation of AhR leads to its translocation inside the nucleus and gene expression, which yields cell differentiation, energy metabolism, microbial defense, and immune cell propagation. Moreover, it may interact with other cells like B-cell and epithelial cell, which are responsible for modulation and maturation, respectively. AhR causes upregulation in the co-stimulatory marker in the DCs and interacts with nuclear factor KB (NF-ĸB) to modulate cell function. Butyrate induces Treg (iTreg) propagation and upregulates the Forkhead box p3 (FOXP3) as a special marker of Treg cell. It may also yield signaling through G-protein coupled receptors (GPRs) which, in turn, facilitates polymorphonuclear (PMN) chemotaxis.The interaction between microbiota and non-immune cells, such as Paneth cells, leads to the secretion of antimicrobial substance, erection of barriers against bacterial pathogens, and regulation of microbiota composition via feedback effect. In addition, the components released from microbiota, such as peptidoglycan, reinforce the maturation of both the immune system and non-immune tissue development. Moreover, microbiota can directly activate the effector cells, e.g., macrophage, to secrete cytokines and propagate Treg cells.

The Value of Sputum Polymerase Chain Reaction for Detection of Nontuberculous Mycobacteria in Cystic Fibrosis Patients with Negative Nontuberculous Mycobacteria Sputum Culture.

Background: Cystic Fibrosis (CF) is a life-threatening autosomal recessive disease. The purpose of this study was to evaluate the value of Polymerase Chain Reaction (PCR) in CF patients with Nontuberculous Mycobacteria (NTM) negative sputum culture. Methods: This is a descriptive cross-sectional study. The population included all children with CF, aged between 5 - 18 years old, with an NTM negative sputum culture. The patient's sputum samples were sent for smear and culture of NTM, RFLP PCR, and PCR sequence. Results: In total, 57 CF patients with negative NTM sputum culture were enrolled. Nine patients (15.78%) had positive sputum PCR for NTM. Among these strains, Mycobacterium simiae was the most common one with 5 cases (8.77% of total positive cases). Conclusion: PCR can be used as an alternative diagnostic method for NTM in CF patients with negative NTM sputum culture, always under clinical suspicion of the disease.

Strain-specific behavior of Mycobacterium tuberculosis in A549 lung cancer cell line.

BACKGROUND: A growing body of evidence has shown the association between tuberculosis (TB) infection and lung cancer. However, the possible effect of strain-specific behavior of Mycobacterium tuberculosis (M.tb) population, the etiological agent of TB infection in this association has been neglected. In this context, this study was conducted to investigate this association with consideration of the genetic background of strains in the M.tb population. RESULTS: We employed the elastic net penalized logistic regression model, as a statistical-learning algorithm for gene selection, to evaluate this association in 129 genes involved in TLRs and NF-κB signaling pathways in response to two different M.tb sub-lineage strains (L3-CAS1and L 4.5). Of the 129 genes, 21 were found to be associated with the two studied M.tb sub-lineages. In addition, MAPK8IP3 gene was identified as a novel gene, which has not been reported in previous lung cancer studies and may have the potential to be recognized as a novel biomarker in lung cancer investigation. CONCLUSIONS: This preliminary study provides new insights into the mechanistic association between TB infection and lung cancer. Further mechanistic investigations of this association with a large number of M.tb strains, encompassing the other main M.tb lineages and using the whole transcriptome of the host cell are inevitable.

The association between interferon lambda 3 and 4 gene single-nucleotide polymorphisms and the recovery of COVID-19 patients.

BACKGROUND: The recent pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has elevated several clinical and scientific questions. These include how host genetic factors influence the pathogenesis and disease susceptibility. Therefore, the aim of this study was to evaluate the impact of interferon lambda 3 and 4 (IFNL3/4) gene polymorphisms and clinical parameters on the resistance and susceptibility to coronavirus disease 2019 (COVID-19) infection. METHODS: A total of 750 SARS-CoV-2 positive patients (375 survivors and 375 nonsurvivors) were included in this study. All single-nucleotide polymorphisms (SNPs) on IFNL3 (rs12979860, rs8099917, and rs12980275) and IFNL4 rs368234815 were genotyped by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: In this study, a higher viral load (low PCR Ct value) was shown in nonsurvivor patients. In survivor patients, the frequency of the favorable genotypes of IFNL3/4 SNPs (rs12979860 CC, rs12980275 AA, rs8099917 TT, and rs368234815 TT/TT) was significantly higher than in nonsurvivor patients. Multivariate logistic regression analysis has shown that a higher low-density lipoprotein (LDL), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and PCR Ct value, and lower 25-hydroxyvitamin D, and also IFNL3 rs12979860 TT, IFNL3 rs8099917 GG, IFNL3 rs12980275 GG, and IFNL4 rs368234815 ∆G/∆G genotypes were associated with the severity of COVID-19 infection. CONCLUSIONS: The results of this study proved that the severity of COVID-19 infection was associated with clinical parameters and unfavorable genotypes of IFNL3/IFNL4 SNPs. Further studies in different parts of the world are needed to show the relationship between severity of COVID-19 infection and host genetic factors.