Notch signaling pathway: a comprehensive prognostic and gene expression profile analysis in breast cancer.

Breast cancer is a complex disease exhibiting a great degree of heterogeneity due to different molecular subtypes. Notch signaling regulates the differentiation of breast epithelial cells during normal development and plays a crucial role in breast cancer progression through the abnormal expression of the Notch up-and down-stream effectors. To date, there are only a few patient-centered clinical studies using datasets characterizing the role of Notch signaling pathway regulators in breast cancer; thus, we investigate the role and functionality of these factors in different subtypes using publicly available databases containing records from large studies. High-throughput genomic data and clinical information extracted from TCGA were analyzed. We performed Kaplan-Meier survival and differential gene expression analyses using the HALLMARK_NOTCH_SIGNALING gene set. To determine if epigenetic regulation of the Notch regulators contributes to their expression, we analyzed methylation levels of these factors using the TCGA HumanMethylation450 Array data. Notch receptors and ligands expression is generally associated with the tumor subtype, grade, and stage. Furthermore, we showed gene expression levels of most Notch factors were associated with DNA methylation rate. Modulating the expression levels of Notch receptors and effectors can be a potential therapeutic approach for breast cancer. As we outline herein, elucidating the novel prognostic and regulatory roles of Notch implicate this pathway as an essential mediator controlling breast cancer progression.

Effect of Statins on Serum level of hs-CRP and CRP in Patients with Cardiovascular Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Several studies have reported that statins have anti-inflammatory effects. Nevertheless, results of clinical trials concerning the effect of statins on the levels of C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) have been inconsistent. Therefore, we performed a systematic review and meta-analysis of randomized clinical trials (RCTs) evaluating the effect of statins on CRP and hs-CRP levels in patients with cardiovascular diseases (CVDs). METHODS: Literature search of the major databases was performed to find eligible RCTs assessing the effect of statins on serum levels of CRP and hs-CRP from the inception until the last week of April 2021. The effect sizes were determined for weighted mean difference (WMD) and 95% confidence intervals (CI). RESULTS: 26 studies were identified (3010 patients and 2968 controls) for hs-CRP and 20 studies (3026 patients and 2968 controls) for CRP. Statins reduced the serum levels of hs-CRP (WMD = -0.97 mg/L; 95% CI: -1.26 to -0.68 mg/L; P < 0.001) and CRP (WMD = -3.05 mg/L; 95% CI: -4.86 to -1.25 mg/L; P < 0.001) in patients with CVDs. Statins decreased the serum levels of hs-CRP in patients receiving both high-intensity and moderate/low-intensity treatments with these drugs. In addition, the duration of treatment longer than 10 weeks decreased hs-CRP levels. Only high-intensity statin treatment could marginally decrease serum levels of CRP in CVDs patients. CONCLUSIONS: This meta-analysis showed the efficacy of statins to reduce the concentrations of CRP and hs-CRP in patients with different types of CVDs.

Effect of curcumin on C-reactive protein as a biomarker of systemic inflammation: An updated meta-analysis of randomized controlled trials.

It has been suggested that curcumin is a potential agent for lowering the levels of C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP), as markers of inflammation. In the current meta-analysis, we attempted to clarify the efficacy of curcumin supplementation in lowering the concentrations of CRP and hs-CRP in patients with autoinflammatory conditions. Nine studies were found evaluating the effect of curcumin on CRP levels, while 23 studies were identified for hs-CRP. CRP concentration was decreased significantly compared to the placebo (WMD = -3.67 mg/L, 95% CI = -6.96 to -0.38, p = 0.02). There was a significant effect of curcumin at dose ≤1,000 mg/day on the CRP concentration. CRP concentration significantly decreased after >10-week intervention compared with placebo.hs-CRP concentration in the intervention group was significantly lower than that of placebo group. A significant effect of curcumin consumption was detected on the serum level of hs-CRP in studies with prescribing ≤1,000 mg/day, and those with ≤10-week duration of intervention. Curcumin consumption resulted in a reduction of hs-CRP in a non-linear fashion with stronger effects with less than 2000 mg curcumin per day. Curcumin seems to be beneficial in decreasing the hs-CRP and CRP levels in proinflammatory settings.

Effect of statins on the plasma/serum levels of inflammatory markers in patients with cardiovascular disease; a systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: The anti-inflammatory properties of statins have been suggested by several researches. However, clinical trials have reported incongruous findings regarding the effect of statins on the levels of inflammatory markers other than high-sensitive C-reactive protein. Therefore, a systematic review and meta-analysis of randomized clinical trials were conducted to illuminate the effect of statins on serum levels of TNF-α, MCP-1, VCAM1, and IL-6 in patients with cardiovascular diseases (CVDs). METHODS: To find eligible studies, a systematic literature search of the main databases were conducted up to July 2021. The calculation of the effect sizes was conducted by standardized mean difference (SMD) and 95% confidence intervals (CI). RESULTS: The pooled analyses revealed that statins significantly reduced the TNF-α concentration (SMD = - 0.99 pg/mL; 95% CI - 1.43 to - 0.55 pg/mL; P < 0.001). Regarding dosage, high intensity (SMD = - 0.65 pg/mL; 95% CI - 1.19 to - 0.10, P = 0.02) and moderate/low (SMD = - 1.16 pg/mL; 95% CI - 1.84 to - 0.47, P = 0.001) intensity statins significantly decreased TNF-α levels. Moderate/low intensity statins administration in < 10 weeks treatment duration decreased serum level of TNF-α (SMD = - 0.91 pg/mL; 95% CI - 1.38 to - 0.44, P < 0.001). Lipophilic statins with high intensity dosage significantly decreased level of TNF-α (SMD = - 0.73 pg/mL; 95% CI - 1.43 to - 0.03, P = 0.04). Statins did not change serum levels of MCP-1, VCAM1, and IL-6 in CVD patients. CONCLUSIONS: The analyses indicated that statins have beneficial effects in decreasing serum levels of TNF-α in patients with CVDs.

Effect of curcumin on proinflammatory cytokines: A meta-analysis of randomized controlled trials.

It has been suggested that curcumin has the potential for lowering inflammation. In the current meta-analysis, we attempted to clarify the efficacy of curcumin/turmeric supplementation in reducing concentrations of interleukin (IL)-1, IL-6, IL-8, and tumor necrosis factor (TNF)-α in patients with an inflammatory background. The main databases were searched to identify eligible trials evaluating the effect of curcumin in reducing IL-1, IL-6, IL-8, and TNF-α in serum up to March 2021. The effect sizes for weighted mean difference (WMD) and 95% confidence intervals (CI) were calculated. Overall, 32 randomized controlled trials (RCTs) were included. There was a significant decrease in the serum levels of IL-1 (WMD = -2.33 pg/ml, 95% CI = -3.33 to -1.34, P < 0.001) and TNF-α (WMD = -1.61 pg/ml, 95% CI = -2.72, -0.51, P < 0.001) compared to the placebo group following treatment. Nonetheless, curcumin/turmeric supplementation was non-significantly associated with reduced levels of IL-6 (WMD = -0.33 pg/ml, 95% CI = -0.99-0.34, P = 0.33) and increased levels of IL-8 (WMD = 0.52 pg/ml, 95% CI = -1.13-2.17, P = 0.53). The dose-responses analysis indicated that curcumin/turmeric supplementation resulted in IL-1 and IL-8 alteration in a non-linear model. Subgroup analysis according to duration and dose of treatment and target population revealed diverse outcomes. Curcumin could have a beneficial effect in reducing the proinflammatory cytokines IL-1 and TNF-α, but not IL-6 and IL-8 levels.

Interleukin-10 Gene Promoter Polymorphisms and Susceptibility to Asthma: Systematic Review and Meta-analysis.

Several studies have previously assessed the association between interleukin (IL)-10 gene polymorphisms and the risk of asthma, leading to conflicting results. To resolve the incongruent outcomes yielded from different single studies, we conducted the most up-to-date meta-analysis of the IL-10 gene rs1800896, rs1800871, and rs1800872 single-nucleotide polymorphisms (SNPs) and susceptibility to asthma. A systematic literature search performed until April 2020, and the pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) were calculated to determine the association strength. Thirty articles comprising 5678 asthmatic patients and 6079 controls met the inclusion criteria. No significant association was found between rs1800872 SNP and susceptibility to asthma across all genetic models in the overall and subgroup analyses. The rs1800871 SNP had only significant association with a decreased risk of asthma in Europeans (OR 0.66, CI 0.53-0.82, P < 0.001). However, rs1800896 SNP was significantly associated with a decreased risk of asthma by dominant (OR 0.67, CI 0.50-0.90, P < 0.001) and heterozygote (OR 0.66, CI 0.49-0.88, P < 0.001) models in the overall analysis. Subgroup analyses indicated significant association of rs1800896 SNP by dominant (OR 0.45, CI 0.28-0.72, P < 0.001) and heterozygote (OR 0.43, CI 0.26-0.70, P < 0.001) models in the African population. The IL-10 rs1800896 SNP confers protection against the risk of asthma, especially in Africans. Additionally, rs1800871 SNP has a protective role against asthma in Europeans.

Effect of resveratrol on C-reactive protein: An updated meta-analysis of randomized controlled trials.

We conducted a meta-analysis on the available randomized clinical trials (RCTs) to assess the role of resveratrol in lowering C-reactive protein (CRP) and high-sensitivity CRP (hs-CRP) levels, as markers of inflammation, in various inflammatory disorders. Literature search through Medline/PubMed, Scopus, ISI Web of Science, and Cochrane Library yielded 35 RCTs (24 studies for hs-CRP and 11 studies for CRP). Pooled results revealed that resveratrol supplementation significantly reduced the hs-CRP (MWD = -0.40 mg/L; 95% CI: -0.70 to -0.09 mg/L; p = .01) and CRP (MWD = -0.31 mg/L; 95% CI: -0.47 to -0.15 mg/L; p < .001) levels in serum. Subgroup analysis revealed that resveratrol in group with ≥10 weeks significantly reduces hs-CRP levels (MWD = -0.48 mg/L; 95% CI: -0.92 to -0.04 mg/L; p = .03) and CRP (WMD = -0.47 mg/L, 95% CI = -0.69 to -0.25, p < .001). A dose of ≥500 mg/day supplementation improves the levels of CRP, but not hs-CRP. This meta-analysis demonstrates that resveratrol consumption is effective in lowering the levels of CRP and hs-CRP in inflammatory conditions, especially if supplementation takes place for ≥10 weeks with ≥500 mg/day.

Interleukin 4 gene polymorphism (-589C/T) and the risk of asthma: a meta-analysis and met-regression based on 55 studies.

BACKGROUND: Numerous investigations have previously evaluated the association of interleukin (IL) 4 gene polymorphisms and the risk of asthma, conferring inconsistent results. To resolve the incongruent outcomes yielded from different single studies, we conducted the most up-to-date meta-analysis of IL4 gene -589C/T (rs2243250) polymorphism and susceptibility to asthma. METHODS: A systematic literature search was performed in ISI web of science, Scopus, Medline/PubMed databases prior to September 2020, and the pooled odds ratio (OR) and their corresponding 95% CI were calculated to determine the association strength. RESULTS: Literature search led to retrieving of 49 publications (55 case-control studies) containing 9572 cases and 9881 controls. It was revealed that IL4 gene -589C/T polymorphism increased the risk of asthma across all genetic models, including dominant model (OR = 1.22), recessive model (OR = 1.17), allelic model (OR = 1.21), and TT vs. CC model (OR = 1.34), but not the CT vs. TT model. The subgroup analysis by age indicated that IL4 gene -589C/T polymorphism was significantly associated with asthma risk in both pediatrics and adults. Additionally, the subgroup analysis by ethnicity revealed significant association in Asian, American, and Europeans. Finally, subgroup analysis by East Asian and non-East Asian populations indicated significant associations. CONCLUSIONS: The current meta-analysis revealed that IL4 gene -589C/T polymorphism was a susceptibility risk in both pediatrics and adults in the whole and different ethnic groups.

PTPN22 gene polymorphism and susceptibility to rheumatoid arthritis (RA): Updated systematic review and meta-analysis.

BACKGROUND: Several genome-wide association studies have revealed a genetic background with respect to susceptibility to rheumatoid arthritis (RA). Although several individual case-control studies have evaluated the role of protein tyrosine phosphatase non-receptor 22 (PTPN22) gene rs2476601 single nucleotide polymorphism (SNP) in conferring a risk for RA, the results have been conflicting. Hence, this meta-analysis was aimed to provide a solution for this issue. METHODS: To search for studies assessing the association between the PTPN22 gene rs2476601 SNP and the risk of RA, a systematic search was conducted in the main databases, including PubMed, Scopus and Web of Science, prior to December 2019. The odds ratio (OR) and corresponding 95% confidence interval (CI) was calculated to assess the possibility of association risk. RESULTS: The literature search identified 52 case-control studies. The pooled analysis detected significant positive association of rs2476601 in all genetic models, including dominant model (OR = 1.69, 95% CI = 1.55-1.84, P < 0.001), recessive model (OR = 2.50, 95% CI = 2.06-3.05, P < 0.001), allelic model (OR = 1.80, 95% CI = 1.60-2.2, P < 0.001), TT versus CC model (OR = 2.79, 95% CI = 2.28-3.41, P < 0.001) and CT versus CC model (OR = 1.59, 95% CI = 1.50-1.67, P < 0.001). Analyses based on population stratification indicated that rs2476601 SNP strongly increased the risk of RA in Caucasians and Africans under all genotype models. CONCLUSIONS: This meta-analysis reports that the PTPN22 gene rs2476601 SNP increases RA risk, especially in Caucasians and Africans.

Interleukin-4 gene polymorphism (C33T) and the risk of the asthma: a meta-analysis based on 24 publications.

BACKGROUND: Previous studies evaluated the association of IL-4 C33T polymorphism and risk of bronchial asthma but failed to establish a consistent conclusive association. In the present meta-analysis, we intend to define a more reliable estimate of the association in the presence of filling published literature. METHODS: An exhaustive search in Web of Science, Scopus, and PubMed databases was performed to identify all relevant publications before September 2020, and 24 publications (28 studies) with 6587 cases and 8408 controls were included in final analysis. The association between polymorphism and risk of asthma were measured by Odd ratios (ORs) and 95% confidence intervals (CIs). Moreover, Cochran's Q and the I2 statistics were used to evaluate the degree of heterogeneity between studies. RESULTS: In the overall study populations, a significant positive association was detected under all genotype models and announced the IL-4 C33T polymorphism as a potential risk factor in the pathogenesis of asthma. In the subgroup analysis by age, a significant association between IL-4 C33T polymorphism and risk of asthma in different age groups was identified in allelic model, which highlighted the predisposing role of the T allele for the asthma risk in all three age groups. Furthermore, the results of subgroup analysis by continent were heterogenous. Accordingly, IL-4 C33T polymorphism was a risk factor in Europeans (all models except heterozygote comparison), Americans (all models except recessive and homozygote comparison) and Asians (just recessive and allelic model). Finally, the ethnicity-specific analysis disclosed a significant association between IL-4 C33T polymorphism and asthma risk in Caucasians (all genotype models except heterozygote comparison), while this association was not significant in African-Americans. CONCLUSIONS: This study suggests that IL-4 C33T polymorphism potentially acts as a risk factor for asthma in different ethnicities and age groups.

Vitamin D receptor gene polymorphism and susceptibility to asthma: Meta-analysis based on 17 case-control studies.

BACKGROUND: During the last decade, several studies have evaluated the potential association between vitamin D receptor (VDR) gene polymorphism and susceptibility to asthma. In spite of valuable findings, the results are still contradictory. Therefore, a comprehensive meta-analysis not only solves discrepancies but provides a clue for future projects. OBJECTIVE: This meta-analysis was performed to identify whether VDR gene polymorphisms (FokI (rs2228570) or TaqI (rs731236) or BsmI (rs1544410) or ApaI (rs7975232)) play a role in the risk of asthma. METHODS: Electronic search of Web of Science, Scopus, and PubMed databases were systematically conducted from their inception until June 2019, to identify all published studies. Eligibility of the studies was confirmed by precise inclusion and exclusion criteria, and the resultant studies were analyzed. RESULTS: A total of 17 studies concerning VDR gene polymorphisms and asthma risk were included in this meta-analysis. The results of pooled analysis indicated a statistically significant association between FokI SNP (dominant model [OR = 0.78, 95% CI, 0.62-0.98, random effect model] and allelic model [OR = 0.81, 95% CI, 0.67-0.98, random effect model]) and TaqI SNP (homozygote contract model [OR = 0.70, 95% CI, 0.54-0.89]) with asthma risk. Moreover, subgroup analysis showed that ethnicity influences asthma risk in Asian, African, and American populations. The sensitivity analyses confirmed the stability of the results. CONCLUSION: This meta-analysis suggests that VDR gene polymorphism is associated with the risk of asthma.

Matrix metalloproteinases (MMPs) family gene polymorphisms and the risk of multiple sclerosis: systematic review and meta-analysis.

BACKGROUND: Several studies have reported the association between polymorphisms in Matrix metalloproteinases (MMPs) gene family and risk of Multiple sclerosis (MS). However, the results have been inconsistent and inconclusive. To resolve this issue, here we performed a systematic review and meta-analysis of the MMP-91562 C/T (rs3918242), MMP-3 (- 1612 5A/6A), and MMP-2 (- 1306 C/T) polymorphisms and susceptibility to MS. METHODS: We conducted a comprehensive systematic search in the major electronic database, including Scopus and PubMed to look up for relevant studies published before December 2019 that surveyed the association between the MMP-91562 C/T (rs3918242), MMP-3 (- 1612 5A/6A), and MMP-2 (- 1306 C/T) polymorphisms and susceptibility to MS. The level of association between the polymorphisms and susceptibility to MS in the polled analysis was determined by calculating the odds ratio (OR) and the corresponding 95% confidence interval (CI). RESULTS: We found 15 studies containing 2430 MS subjects and 2304 controls. A statistically significant association was observed in the all five comparisons of the MMP-91562 C/T polymorphism and MS risk as follows: dominant model (OR = 1.62, 95% CI = 1.03-2.53, P = 0.03), recessive model (OR = 2.69, 95% CI = 1.68-4.29, P < 0.001), allelic model (OR = 1.51, 95% CI = 1-2.28, P = 0.04), TT vs. CC model (OR = 3.20, 95% CI = 1.87-5.46, P < 0.001), and CT vs. CC model (OR = 1.53, 95% CI = 1.02-2.28, P = 0.04). CONCLUSIONS: Our meta-analysis revealed significant association of MMP-9 (- 1562 C/T) Single-nucleotide polymorphism (SNP) with MS susceptibility that increased the disease risk.

Vitamin D receptor gene polymorphisms and the risk of the type 1 diabetes: a meta-regression and updated meta-analysis.

BACKGROUND: The association between the polymorphisms in the vitamin D receptor (VDR) gene and the risk of type 1 diabetes mellitus (T1DM) has been evaluated in several studies. However, the findings were inconclusive. Thus, we conducted a meta-analysis to comprehensively evaluate the effect of VDR gene polymorphisms on the risk of T1DM. METHODS: All relevant studies reporting the association between VDR gene polymorphisms and susceptibility to T1DM published up to May 2020 were identified by comprehensive systematic database search in ISI Web of Science, Scopus, and PubMed/MEDLINE. Strength of association were assessed by calculating of pooled odds ratios (ORs) and 95% confidence intervals (CIs). The methodological quality of each study was assessed according to the Newcastle-Ottawa Scale. To find the potential sources of heterogeneity, meta-regression and subgroup analysis were also performed. RESULTS: A total of 39 case-control studies were included in this meta-analysis. The results of overall population rejected any significant association between VDR gene polymorphisms and T1DM risk. However, the pooled results of subgroup analysis revealed significant negative and positive associations between FokI and BsmI polymorphisms and T1DM in Africans and Americans, respectively. CONCLUSIONS: This meta-analysis suggested a significant association between VDR gene polymorphism and T1DM susceptibility in ethnic-specific analysis.

The association between Matrix Metallo-proteinases-9 (MMP-9) gene family polymorphisms and risk of Coronary Artery Disease (CAD): a systematic review and meta-analysis.

BACKGROUND: We performed a systematic review and meta-analysis of the Matrix metalloproteinases (MMP)-9 (C1562T), MMP-9 (R279Q), MMP-9 (P574R) and MMP-9 (R668Q) polymorphisms and risk of Coronary Artery Disease (CAD). METHODS: After a systematic literature search, pooled odds ratio (OR) and their corresponding 95% confidence interval (CI) were used to evaluate the strength of the association. RESULTS: We identified 40 studies with 11,792 cases and 8280 controls for C1562T, 7 case-control studies with 5525 cases and 2497 controls for R279Q, 2 studies with 1272 cases and 785 controls for P574R, and 2 studies with 1272 cases and 785 controls for R668Q. MMP-9 (C1562T) polymorphism was associated with increased risk of CAD under dominant model (OR = 1.41, P < 0.001), recessive model (OR = 1.59, P < 0.001), allelic model (OR = 1.38, P < 0.001), TT vs. CC model (OR = 1.70, P < 0.001), and CT vs. CC model (OR = 1.35, P < 0.001). Moreover, the subgroup analysis based on the continent of the study populations in this SNP indicated strong significant association in Asians but not in Europeans. Subgroup analysis was not performed in Africa, America and Oceania, due to lack of sufficient data. CONCLUSIONS: Our meta-analysis revealed that MMP-9 (C1562T) SNP conferred a susceptibility risk for CAD in the overall analysis and Asian population. The overall analysis and subgroup analysis of the other three SNPs reject the association between MMP-9 polymorphisms and the risk of CAD. Although the results should interpret with caution because of small sample size of included studies in these three SNPs.

Vitamin D receptor gene polymorphisms and susceptibility to urolithiasis: a meta-regression and meta-analysis.

BACKGROUND: The currently available data with respect to the association between vitamin D receptor (VDR) gene polymorphism and risk to urolithiasis are inconclusive and inconsistent. Hence, an exhaustive meta-analysis can solve the discrepancies and provide a hint for upcoming investigations. Herein, a meta-analysis was carried out to attain a conclusive estimate of the association between VDR gene single nucleotide polymorphisms (SNPs) and urolithiasis risk. METHODS: The major databases, including ISI Web of science, Scopus, and PubMed/MEDLINE were searched systematically from until June 2020 to retrieve all relevant studies. Association between VDR gene polymorphisms, including FokI (rs2228570), TaqI (rs731236), BsmI (rs1544410), and ApaI (rs7975232), and urolithiasis risk was evaluated using pooled odds ratio (OR) and their corresponding 95% confidence interval (CI). Additionally, to seek for the potential source of heterogeneity, meta-regression analyses were exerted. RESULTS: Literature search led to finally finding of 33 studies evaluating the VDR gene SNPs and urolithiasis risk. It was observed that none of the four SNPs were significantly associated with urolithiasis predisposition. However, subgroup analysis confirmed higher risk of urolithiasis in East-Asian and Caucasian population with ApaI and TaqI gene polymorphism. The analyses of sensitivity acknowledged the results stability. CONCLUSION: Although this meta-analysis did not support the association of FokI, TaqI, BsmI, and ApaI in the overall polled analysis, it suggests that ApaI and TaqI SNPs is associated with increased risk of urolithiasis in East-Asian and Caucasians populations.

Association between vitamin D receptor (VDR) polymorphisms and the risk of multiple sclerosis (MS): an updated meta-analysis.

BACKGROUND: The association between the Vitamin D Receptor (VDR) gene polymorphism and the risk of Multiple sclerosis (MS) has been evaluated in several researches. However, the findings were inconsistent and inconclusive. Therefore, we set out a meta-analysis of all eligible published case-control studies to obtain an exact evaluation of the association between VDR gene polymorphisms and MS. METHOD: All relevant studies reporting the association between the VDR gene FokI (rs2228570), or/and TaqI (rs731236) or/and BsmI (rs1544410) or/and ApaI (rs7975232) polymorphisms and susceptibility to MS published up to May, 2019 were identified by comprehensive systematic search in the electronic database of web of science, Scopus, and PubMed. After that, the strength of association between VDR gene polymorphisms and susceptibility to MS was evaluated by odds ratio (OR) and 95% confidence interval (CI). RESULTS: A total of 30 case-control studies were included in the meta-analysis. The overall results suggested a significant association between TaqI polymorphism and MS risk under heterozygote genetic model (OR = 1.27, 95%CI = 1.01-1.59, random effect). Moreover, the pooled results of subgroup analysis declined presence of significant association under all defined genetic model. In subgroup analysis, BsmI polymorphisms was associated with increased risk of MS under recessive model in Asian populations. On the other hand, ApaI polymorphism was associated with decreased risk of MS under recessive and aa vs. AA model in Asian populations. CONCLUSION: This meta-analysis suggested a significant association between TaqI polymorphism and MS susceptibility. Furthermore, BsmI polymorphism was associated with increased risk of MS in Asian populations. In contrast, ApaI polymorphism was associated with decreased risk of MS in Asian populations. Future large-scale studies on gene-environment and gene-gene interactions are required to estimate risk factors and assist early diagnosis of patients at high risk for MS.

Association of nod-like receptor protein-3 single nucleotide gene polymorphisms and expression with the susceptibility to relapsing-remitting multiple sclerosis.

Nod-like receptor protein 3 (NLRP3) inflammasome is a multi-protein complex that controls the production of pro-inflammatory cytokines, IL-18 and IL-1ß, through caspase-1 activation. These inflammatory cytokines play an important role in the development of multiple sclerosis (MS). The inflammasome NLRP3 gene variations and expression level have been suggested to affect the immune system activity. This case-control study was performed to determine the association of NLRP3 genetic variants and differential expression with MS. We analysed four common single nucleotide polymorphisms (SNPs) of NLRP3 (rs-10754558, rs-35829419, rs-3806265, rs-4612666) in a group of 150 Iranian patients with relapsing-remitting MS (RRMS) in comparison with 100 healthy controls. The genotyping was performed using the TaqMan method. For the analysis of NLRP3 gene expression level, we studied a group of 37 RRMS patients (18 patients at relapse phase and 19 at remission phase, treated with IFN-ß) in comparison with 22 healthy controls using real-time PCR. In this study, we found that NLRP3 rs3806265 C allele and CC genotype were significantly more frequent in the RRMS patients (p value = 0.03 OR = 1.66, 95% CI = 1.14-2.43) and p value = 0.04, OR = 3.26, 95% CI = 1.19-8.93, respectively), while the frequency of T allele significantly decreased in controls (p value = 0.03, OR = 0.6, 95% CI = 0.41-0.87). The frequency of CG genotype at position rs10754558 was also significantly higher in the controls compared with patients (p value = 0.03, OR = 0.5, 95% CI = 0.30-0.80). Moreover, expression level of the NLRP3 in patients at remission phase was significantly reduced in comparison with patients at relapse phase and also healthy controls (p = 0.01 and p = 0.04, respectively). The association of NLRP3 polymorphisms with the susceptibility of MS and its reduced expression after IFN-ß therapy, support the idea that NLRP3 inflammasome could have a critical role in inflammatory responses in MS.

Statin Therapy and Lipid Indices in Chronic Kidney Disease: A Systematic Review and Meta-analysis of Randomized Control Trials.

BACKGROUND: Several studies have demonstrated the improvement in serum lipoproteins by statins in patients with Chronic Kidney Diseases (CKDs), including End-Stage Renal Disease (ESRD). However, the results of these studies are inconclusive. AIM: We aimed to systematically investigate the effect of statins on lipid profiles of patients with CKD by performing a meta-analysis of Randomized Controlled Trials (RCTs). METHODS: Major electronic databases (Scopus, MEDLINE/PubMed, and ISI Web of Science) were searched from inception to August, 2023, to find randomized controlled trials (RCTs) evaluating the effect of different statins on serum lipoproteins in CKD patients. Weighted Mean Difference (WMD) with 95% Confidence Intervals (CI) was used to estimate the effect size. Trial Sequential Analysis (TSA) was performed to confirm the robustness of the evidence. RESULTS: A total of 18 publications were identified. It was found that statins reduced serum levels of Low-Density Lipoprotein (LDL)-C (WMD = -27.81 mg/dl, 95% CI = -34.47 to -21.15, P < 0.001) and total cholesterol (WMD = -25.44 mg/dl, 95% CI = -34.71 to -16.18, P < 0.001) in patients with CKD compared to the control group. Nonetheless, the effect of statins on High-Density Lipoprotein (HDL)-C (WMD = 0.57 mg/dl, 95% CI = -0.71 to 1.85, P = 0.38) and Triglyceride (TG) (WMD = -9.08 mg/dl, 95% CI = -22.22 to 2.06, P = 0.11) was not statistically significant. The results of TSA confirmed the robustness of the evidence and were consistent with the pooled effect size. The findings of subgroup analysis and time response analysis were also significant. CONCLUSION: It was found that statin therapy reduced the levels of LDL-C and total cholesterol in patients with CKD.

High purity and recovery of native filamentous hemagglutinin (FHA) from Bordetella pertussis using affinity chromatography.

Filamentous hemagglutinin (FHA) is a critical adhesion molecule produced by Bordetella pertussis (BP), the causative agent of highly contagious respiratory infection known as whooping cough. FHA plays a pivotal role in the pathogenesis of whooping cough and is a key component of acellular pertussis vaccines (aPV). However, conventional purification methods for FHA often involve labor-intensive processes and result in low purity and recovery rates. Therefore, this study explores the use of monoclonal and polyclonal antibodies as specific tools to achieve highly pure and efficient FHA purification. To generate FHA-specific antibodies, polyclonal antibodies were produced by immunizing sheep and monoclonal antibodies (MAbs) were generated by immunizing mice with recombinant and native FHA. The MAbs were selected based on affinity, isotypes, and specificity, which were assessed through ELISA and Western blot assays. Two immunoaffinity columns, one monoclonal and one polyclonal, were prepared for FHA antigen purification. The purity and recovery rates of these purifications were determined using ELISA, SDS-PAGE, and immunoblotting. Furthermore, the MAbs were employed to develop an ELISA assay for FHA antigen concentration determination. The study's findings revealed that immunoaffinity column-based purification of FHA resulted in a highly pure antigen with recovery rates of approximately 57% ± 6.5% and 59% ± 7.9% for monoclonal and polyclonal columns, respectively. Additionally, the developed ELISA exhibited appropriate reactivity for determining FHA antigen concentration. This research demonstrates that affinity chromatography is a viable and advantageous method for purifying FHA, offering superior purity and recovery rates compared to traditional techniques. This approach provides a practical alternative for FHA purification in the context of aPV development.

Effect of Statins on Serum Levels of TNF-alpha and Interleukin-6 in Patients with Kidney Disease: A Meta-analysis of Randomized Clinical Trials.

BACKGROUND AND OBJECTIVES: Some clinical trials have indicated the beneficial effects of statins in patients with kidney disease, while others have reported no positive effect of statins in these patients. We conducted this meta-analysis to identify the effects of statins on serum levels of interleukin-6 (IL-6) and Tumor Necrosis Factor Alpha (TNF-α) in patients with kidney disease. DESIGNS AND METHODS: A systematic literature search was performed using PubMed, Scopus, and Web of Science databases to identify all studies published from inception to August, 2022. The major outcome variable was the Weighted Mean Difference (WMD). Eligible studies were stratified based on target population, intervention duration, dosage and type of statins, and solubility of statins. RESULTS: Meta-analysis performed on seven publications (8 studies), including 213 patients with kidney disease and 188 control individuals, indicated that the concentration of IL-6 was marginally decreased in patients with kidney disease following statin therapy disease (WMD = -1.15 pg/mL; 95% CI = -2.33 to 0.04, P = 0.05, 2 =68.5%)). The findings of subgroup analysis based on the dosage of statins showed that neither highintensity nor moderate/low-intensity statin treatment could significantly influence the serum level of IL-6. Lipophilic statins were more effective than hydrophilic statins, and they marginally decreased the levels of IL6 (WMD = -1.21 pg/mL; 95% CI = -2.43 to 0, P = 0.05, I2 = 55.7%)). Meta-analysis of four publications (five studies) with 157 patients with kidney disease and 132 control subjects showed that statins reduced the serum levels of TNF-α in patients with kidney disease when compared with control individuals (WMD= -2.66 pg/mL; 95% CI = -4.26 to -1.06, P < 0.001, I2 = 63%). CONCLUSION: Statins only marginally decreased the concentration of IL-6 in patients with kidney disease, but neither high-intensity nor moderate/low-intensity statin treatment could significantly influence the level of IL6. However, statins reduced serum levels of TNF-α in patients with kidney disease.