Exploring the relationship between gut microbiome modulation and blood pressure in type 2 diabetes: An umbrella review.

AIMS: Given the epidemic proportions of type 2 diabetes mellitus (T2DM) globally, it's crucial to comprehensively understand the factors influencing its management. The gut microbiome, known for its influence on various aspects of health, has emerged as a potential regulator of blood pressure in individuals with T2DM. This umbrella review aimed to consolidate the findings of existing meta-analyses investigating the impact of gut microbiome modulation on systolic and diastolic blood pressure in T2DM patients. DATA SYNTHESIS: Adhering to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, we systematically searched PubMed, Scopus, and Web of Science databases from inception to July 2023. Quality assessment was performed using the AMSTAR2 and GRADE checklists. Statistical analyses were conducted using Comprehensive Meta-Analysis (CMA) version 3. A total of 6 meta-analyses meeting the inclusion criteria were included. The results revealed a significant association between microbial modulation and diastolic blood pressure (SMD: -0.133; 95% CI: -0.219 to -0.048; P = 0.002). However, the effect of gut microbial modulation on systolic blood pressure did not reach statistical significance (SMD: -0.077; 95% CI: -0.162 to 0.009; P = 0.078). CONCLUSION: This study found that modulating the gut microbiome had a statistically significant impact on diastolic blood pressure in individuals with type 2 diabetes mellitus (T2DM). However, no significant effect was observed on systolic blood pressure. While high-quality meta-analyses reported favorable outcomes, caution is warranted due to the low clinical importance, diversity in study populations, and variations in interventions.

Concentration of polycyclic aromatic hydrocarbons (PAHs) in bread and health risk assessment across the globe: A systematic review and meta-analysis.

Although bread is the principal food in most countries, polycyclic aromatic hydrocarbons (PAHs) may be present and pose a potential risk to consumers. The aim of this review is to provide a comprehensive report on the concentration and health risks associated with PAHs in bread around the world. Various databases, such as Scopus, PubMed, Science Direct, and Google Scholar, were searched from their beginnings until December 2023 for this systematic review, which included 34 potentially relevant articles with data relating to 1057 bread samples. Utilizing a multilevel regression modeling approach, the study evaluated various factors such as fuel type, bread type, and geographical location. Following the initial evaluation, in 26.47% and 20.28% of all studies, the levels of Bap and PAH4 were higher than the permissible limit values, respectively. Based on the isomer ratios, 55.88% of the studies associated the presence of PAHs in bread samples with pyrogenic/coal combustion sources. According to the carcinogenic risk results, bread consumers in all studies have been exposed to moderate or high levels of carcinogenicity. The most significant risk levels are associated with the consumption of bread in Egypt, Kuwait, Iran, and India. Moreover, meta-regression analysis demonstrated significantly higher toxicity equivalent quotient and cancer risk mean values in bread baked using fossil fuels compared to other sources (p < .05). The high concentrations of PAHs, especially Benzo[a]pyrene, in bread pose a serious public health risk. Stringent regulations and monitoring are crucial to reduce contamination. Further research is necessary to develop safe processing methods to remove PAHs in bread.

Genetic Variations of Angiotensinogen, Angiotensin Converting Enzyme, and Angiotensin Type 1 Receptor with the Risk of Pulmonary Tuberculosis.

There is little data regarding the impact of renin-angiotensin system (RAS) gene polymorphisms on tuberculosis. The current study designed to survey the possible association between RAS polymorphisms and the risk of pulmonary tuberculosis (PTB) in a sample of the southeast Iranian population. This case-control study was done on 170 PTB patients and 170 healthy subjects. The AGT rs699 C>T, ACE rs4341 C>G and AT1R rs5186 C>A variants were genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) and ACE rs4646994 (287bp I/D) variant by PCR method. Regarding AT1R rs5186 A>C polymorphism, the findings revealed that AC genotype and C allele significantly decreased the risk of PTB (OR=0.39, 95% CI=0.22-0.67, p=0.001, and OR=0.53, 95% CI=0.25-0.72, p=0.002, C vs. A, respectively). The TC genotype and C allele of AGT rs699 T>C significantly associated with decreased the risk of PTB (OR=0.45, 95% CI=0.28-0.74, p=0.002, TC vs. TT and OR=0.51, 95% CI=0.32-0.80, p=0.005, C vs. T, respectively). The ID genotype of ACE 287bp I/D significantly increased the risk of PTB (OR=1.88, 95% CI=1.12-3.17, p=0.017). Our finding did not support an association between ACE rs4341 C>G variant and the risk of PTB. In summary, the findings revealed an association between AT1R rs5186 A>C, AGT rs699 T>C and ACE 287bp I/D polymorphisms and the risk of PTB in a sample of the southeast Iranian population. Further investigation with higher sample sizes and diverse ethnicities are required to confirm our findings.

Microbiological quality of hospital-prepared blenderised tube feeding.

BACKGROUND: Contaminated blenderised tube feeding (BTF) causes numerous infections in patients with deficient immune systems. The microbial quality of BTF should be thoroughly monitored to reduce the risks of microbial agents and prevent food safety problems such as food poisoning and food-borne illnesses. The aim of this study was to survey the contamination rate of BTF samples prepared in the teaching hospitals in Mashhad, Iran. METHODS: This study was conducted on 24 samples of BTF prepared in four teaching hospitals in Mashhad city; the samples were collected randomly. Then specific culture media were used for detected and counted Listeria monocytogenes, Salmonella spp., Staphylococcus aureus, Clostridium perfringens, Bacillus cereus, coliforms and Escherichia coli. The final confirmation of the isolates was performed using polymerase chain reaction. RESULTS: The total bacterial count was determined in the BTF samples and compared with the Food and Drug Administration medical food standards; 91.6% of the samples had 5.2 ± 0.1 log CFU/ml microbial bacterial contamination considering the standard range. The mean prevalence of contamination in these samples was measured for coliforms 4.9 ± 0.17 log CFU/ml, B. cereus 3.6 ± 0.16 log CFU/ml, S. aureus 3.7 ± 0.15 log CFU/ml and C. perfringens 4.7 ± 0.08 log CFU/ml (p < 0.05). Moreover, E. coli 11 (45.8%), Salmonella spp. 9 (37.5%) and L. monocytogenes 17 (70.8%) samples were detected. CONCLUSION: Given the high consumption of BTF and the transmission of food contamination to hospitalised patients, it is essential to improve the hygienic conditions at the site of BTF preparation to prevent re-contamination.

Learning English with electronic textbooks on mobile devices: Impacts on university students' vocabulary development.

The current study examined the use of electronic textbooks designed as mobile applications for learning vocabulary in English among Iranian university students. To this end, 95 university students in an experimental (N = 50) and a control group (N = 45) participated in the study. An explanatory sequential mixed methods design was employed and over an academic semester, the participants used either traditional materials or mobile-based electronic textbooks for learning 600 words in English. To assess the outcomes from different learning conditions, receptive knowledge of the target vocabulary items was tested in three junctures of time (i.e. pre-, post-, and delayed post-test). Additionally, open-ended questionnaires and interviews were used to collect qualitative data from the experimental group to further investigate their perceptions of using mobile-based electronic textbooks for vocabulary learning. The findings revealed a significant main effect for time and both groups significantly improved their vocabulary knowledge from pre-test to post-test. Moreover, a significant main effect was found for using electronic textbooks on mobile devices, and the experimental group outperformed the control group on the post- and delayed post-tests. The qualitative findings revealed three perceived benefits, namely episodic learning, easy access to materials, and enhanced enjoyment for mobile assisted vocabulary learning through electronic textbooks. The perceived challenges were related to health concerns, distractions associated with mobile environments, and external pressure resulting from excessive mobile use among the participants. In general, the findings of the study shed light on the potential offered by mobile-based textbooks for learning English vocabulary, with implications for teachers and materials developers in language teaching programs.

Methicillin- and Vancomycin-Resistant Staphylococcus aureus and Vancomycin-Resistant Enterococci Isolated from Hospital Foods: Prevalence and Antimicrobial Resistance Patterns.

This study aimed to investigate the prevalence of Methicillin- and Vancomycin-Resistant Staphylococcus aureus (MRSA, VRSA) and Vancomycin-Resistant Enterococcus (VRE) of hospital food samples in Mashhad, Iran. A total of 357 hospital food samples were collected from 13 hospitals. Enterococcus spp. and Staphylococcus aureus were identified using conventional cultural techniques following genotypic confirmation by PCR. The antibiotic resistance patterns of MRSA, VRSA, and VRE strains were analyzed using the disk diffusion methods. The prevalence of S. aureus and MRSA were 24.37% (87/357) and 22.98% (20.87), respectively. In addition, the vanB gene involved in vancomycin resistance was detected in 1.14% of the S. aureus strains. Enterococci and VRE had a prevalence of 15.4% (55/357) and 21.81% (12/55), respectively. Meat, chicken barbecues, and salad were the most commonly contaminated samples with S. aureus, MRSA, Enterococci, and VRE. PCR detected two vancomycin resistance genes, including vanA (1.81%, 1.55) and vanC2 (20%, 11.55) genes. MRSA strains revealed the highest resistance against penicillin, erythromycin, clindamycin, azithromycin, tetracycline, and gentamicin. The VRSA isolates were resistant to penicillin, ampicillin, oxacillin, cefoxitin, clindamycin, erythromycin, gentamicin, and trimethoprim-sulfamethoxazole. Furthermore, VRE isolates exhibited the highest resistance against quinupristin-dalfopristin, erythromycin, and tetracycline. The results of this study indicated that hospital foods might act as a reservoir of Enterococci spp. and S. aureus strains, which can transfer antibiotic resistance. Moreover, multidrug resistance (MDR) in some MRSA, VRSA, and VRE isolates represents a serious threat to susceptible persons in hospitals.

Dietary total antioxidant capacity and severity of stenosis in patients with coronary artery disease.

Aim: Coronary artery disease (CAD) is a major cause of mortality worldwide. Many studies suggest that dietary antioxidant can offer significant protection against stroke, heart failure, and coronary heart disease. However, there is no study that assessed the association between dietary TAC and severity of stenosis in patients with CVD. The aim of this study was to investigate the association of dietary TAC and severity of stenosis in patients with coronary artery disease. Methods: Dietary and medical History of 160 patients with CAD were assessed. The extent of Stenosis was determined using the Gensini score. Dietary history was investigated by food frequency questionnaire (FFQ), and Dietary TAC was calculated by multiplying the average frequency of intake of each food by oxygen radical absorbance capacity (ORAC) content. Results: Across the Gensini score quartiles the dietary TAC, dietary hydrophilic TAC, dietary lipophilic TAC, and dietary phenolic TAC values were significantly increased in the highest quartile compared with the lowest quartile (dietary TAC (mmolTE/100 g):17.5 ± 1.82 vs. 11.2 ± 1.90; dietary hydrophilic TAC (mmolTE/100 g): 16.56 ± 1.29 vs. 10.74 ± 1.81; dietary lipophilic TAC (mmolTE/100 g): 0.55 ± 0.12 vs. 0.23 ± 0.09; dietary phenolic TAC (mmolTE/100 g):1.84 ± 0.31 vs. 0.98 ± 0.21; (P < 0.001 for all)). However, a non-significant association between the plasma TAC and Gensini quartiles was observed (P = 0.789). Multivariate regression analysis showed that dietary TAC (Beta = -0.53; P < 0.001) was statistically significant independent predictors that associated with the Gensini score values. Conclusions: There was a significant association between dietary TAC and severity of stenosis in patients with coronary artery disease.

Association of miR-499 Polymorphism and Its Regulatory Networks with Hashimoto Thyroiditis Susceptibility: A Population-Based Case-Control Study.

Hashimoto thyroiditis (HT) is a common autoimmune disorder with a strong genetic background. Several genetic factors have been suggested, yet numerous genetic contributors remain to be fully understood in HT pathogenesis. MicroRNAs (miRs) are gene expression regulators critically involved in biological processes, of which polymorphisms can alter their function, leading to pathologic conditions, including autoimmune diseases. We examined whether miR-499 rs3746444 polymorphism is associated with susceptibility to HT in an Iranian subpopulation. Furthermore, we investigated the potential interacting regulatory network of the miR-499. This case-control study included 150 HT patients and 152 healthy subjects. Genotyping of rs3746444 was performed by the PCR-RFLP method. Also, target genomic sites of the polymorphism were predicted using bioinformatics. Our results showed that miR-499 rs3746444 was positively associated with HT risk in heterozygous (OR = 3.32, 95%CI = 2.00-5.53, p < 0.001, CT vs. TT), homozygous (OR = 2.81, 95%CI = 1.30-6.10, p = 0.014, CC vs. TT), dominant (OR = 3.22, 95%CI = 1.97-5.25, p < 0.001, CT + CC vs. TT), overdominant (OR = 2.57, 95%CI = 1.62-4.09, p < 0.001, CC + TT vs. CT), and allelic (OR = 1.92, 95%CI = 1.37-2.69, p < 0.001, C vs. T) models. Mapping predicted target genes of miR-499 on tissue-specific-, co-expression-, and miR-TF networks indicated that main hub-driver nodes are implicated in regulating immune system functions, including immunorecognition and complement activity. We demonstrated that miR-499 rs3746444 is linked to HT susceptibility in our population. However, predicted regulatory networks revealed that this polymorphism is contributing to the regulation of immune system pathways.

LMO1 polymorphisms and the risk of neuroblastoma: Assessment of meta-analysis of case-control studies.

Neuroblastoma (NB), a neuroendocrine tumour, is one of the most prevalent cancers in children. The link between LMO1 polymorphisms and NB has been investigated by several groups, rendering inconclusive results. Here, with this comprehensive systematic review and up-to-date meta-analysis, we aim to distinctively elucidate the possible correlation between LMO1 polymorphisms and NB susceptibility. Eligible studies were systematically researched and identified using PubMed, Web of Science and Scopus databases up to 10 February 2019. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the associations. Our findings revealed that rs110419 and rs2168101 polymorphisms were significantly associated with a decreased risk of NB in all genetic models. In addition, the rs4758051 variant appeared protective against NB in homozygous, dominant and allele genetic models, whereas the rs10840002 variant markedly decreased the risk of NB in the allele model. In contrast, the rs204938 polymorphism showed a positive association with NB susceptibility in allele genetic models. In summary, our meta-analysis is the first to provide clear evidence of an association between specific polymorphisms of LMO1 and susceptibility to NB. Of note, additional larger well-designed studies would be helpful to further evaluate and confirm this association.

An association study of polymorphisms in the H19 imprinted gene in an Iranian population with the risk of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies that causes problems in female fertility at the reproductive age. PCOS is a multifactorial disease, with genetic factors playing a crucial role in its development. H19 is a long non-coding RNA (lncRNA) expressed from the maternal chromosome, which is correlated with PCOS. In this study, 115 women suffering from PCOS and 130 healthy women with regular menstrual cycles were recruited as case and control groups, respectively. After the extraction of genomic DNA, the restriction fragment length polymorphism polymerase chain reaction was employed for genotyping of rs2067051G>A and rs3741219T>C. Statistical analysis was done using SPSS package V.22 for Windows. In silico analysis was recruited to determine the effects of SNPs on the secondary structure of gene transcript as well as miRNA binding sites. The obtained data showed that the A allele of rs2067051G>A was associated with the high risk of PCOS (OR = 2.00, 95%CI = 1.38-2.91, P = 0.00). AG and AA genotypes led to a 3.64- and (about) a five-fold increase in the risk of PCOS, respectively (95%CI = 2.02-6.54, P = 0.00, and 95%CI = 1.51-16.52, P = 0.00, respectively). These variants caused a significant increase in the risk of this disorder in all genotype models except in the recessive model. However, no association was found between rs3741219T>C and the increased risk of PCOS, either in the allele or in the genotype models. According to the findings, rs2067051G>A is associated with an increased risk of PCOS in the Iranian population.

Havachoobe (Onosma dichroanthum Boiss) Root Extract Decreases the Hepatitis B Virus Surface Antigen Secretion in the PLC/PRF/5 Cell Line.

BACKGROUND: Many efforts are currently focused on functional treatment of the hepatitis B virus (HBV). This can be done by suppressing the secretion of HBV surface antigen (HBsAg). Scientific communities are very interested in natural products in that respect. OBJECTIVE: Use of root extract of Havachoobe (Onosma dichroanthum BoissI), a Northern Iranian native medical herb, for assessment of its anti-HBsAg secretion activity. METHODS: Havachoobe had been bought at a nearby apothecary store. Plant root extract was obtained using a hydroalcoholic process. Cytotoxic activity of the extract was examined on PLC/PRF/5 cells using MTT assay. ELISA has been used to measure HBsAg in the treated cell line supernatants. In addition, real-time PCR analysis was performed to evaluate the expression of HBsAg before and after treatment of Onosma in vitro. RESULTS: The results showed very low root extract cytotoxicity at concentrations under 8 µg/mL. Tissue culture infectious dose 50 was obtained at 63.78 µg/mL. In a dose-dependent and time-dependent manner, a significantly reduced HBsAg secretion was observed at a concentration of 8 ppm at 12 h post-treatment. The real-time PCR result showed relative decreased HBsAg expression at all doses at 12 h post-treatment time. DISCUSSION: In this study, we first reported anti-HBsAg activity on an Iranian herbal medicine. Havachoobe root extract was shown to be able to inhibit HBsAg in a dose-dependent and time-dependent manner. We find the extract exerts its inhibitory effect of HBsAg by targeting transcription of HBsAg.

Association of Genetic Polymorphisms of GREM1 Gene with Susceptibility to Non-Syndromic Cleft Lip with or without Cleft Palate in an Iranian Population.

Background: Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is common congenital birth anomaly with multifactorial etiology. The GREM1 gene has been proposed to play a role in oral clefts development.Objective: The aim of the present study was to evaluate the correlation between GREM1 polymorphisms and the risk of NSCL/P in an Iranian population.Methods: Genotyping of rs7162202, rs12915554, rs3743105, rs1129456, and rs10318 polymorphisms of GREM1 gene in 150 NSCL/P and 152 healthy subjects was determined by the PCR-RFLP or T-ARMS-PCR.Results: The findings showed that the rs12915554 variant significantly increased the risk of NSCL/P in heterozygous (OR = 4.20, 95%CI = 2.46-7.11, p < 0.0001, AC vs AA), and allele (OR = 3.17, 95%CI = 2.00-5.08, p < 0.0001, C vs A) genetic models. The rs3743105 polymorphism was correlated with reduced risk of NSCL/P in heterozygous (OR = 0.49, 95%CI = 0.29-0.83, p = 0.008, AG vs GG) and dominant (OR = 0.54, 95%CI = 0.33-0.89, p = 0.018, GA + AA vs GG) genetic models. The rs1129456 variant was positively associated with the risk of NSCL/P in heterozygous (OR = 2.91, 95%CI = 1.12-7.38, p = 0.028, AT vs AA) and allele (OR = 2.80, 95%CI = 2.80-6.95, p = 0.031, T vs C). The rs10318 polymorphism significantly reduced NSCL/P risk in homozygous (OR = 0.20, 95%CI = 0.06-0.67, p = 0.013, TT vs CC), dominant (OR = 0.57, 95%CI = 0.36-0.91, p = 0.019, CT + CC vs CC), recessive (OR = 0.24, 95%CI = 0.07-0.76, p = 0.031, TT vs CT + CC), and allele (OR = 0.57, 95%CI = 0.38-0.84, p = 0.005, T vs C). No correlation was observed between rs7162202 polymorphism and NSCL/P.Conclusion: The findings support that GREM1 polymorphisms are involved in NSCL/P susceptibility in an Iranian population.

Association Study of MBL2 Gene Polymorphisms and Risk of Tuberculosis in Southeast of Iran.

Mannose-binding lectin (MBL) is an acute phase protein which recognizes the pathogens through its carbohydrate recognition domain. It is an important part of human innate immunity. The aim of the current study was to evaluate the impact of MBL2 polymorphism on pulmonary tuberculosis in a number of patients from the southeast of Iran. In this case-control study, 2 MBL gene polymorphisms (rs1800450, rs7095891) were genotyped using PCR-RFLP method and polymerase chain reaction for detection of 34bp ins/del of MBL2 gene (rs777980157) polymorphism. The study included 170 patients with PTB (pulmonary tuberculosis) and 175 control subjects. The findings indicated that the GA (GA vs. GG: OR=0.172, 95% CI=0.107-0.275, P<0.001) (OR - odds ratio; CI - confidence interval) genotype as well as GA+AA (GA+AA vs. GG: OR=0.191, 95% CI=0.120-0.302, P<0.001) genotype of rs1800450 reduced the risk of PTB compared to GG genotype. The rs7095891 variant significantly decreased the risk of PTB in codominant (GA vs. GG: OR=0.118, 95% CI=0.054-0.258, P<0.001; and AA vs. GG: OR=0.029, 95% CI=0.01-0.082, P<0.001), dominant (GA+AA vs. GG: OR=0.095, 95% CI=0.044-0.207, P<0.001) and recessive (AA vs. GA+GG: OR=0.172, CI=0.081-0.365, P<0.001) inheritance models. No significant relationship was identified between the rs777980157 variant and PTB risk/protection. In conclusion, we found that the MBL2 rs1800450 and rs7095891 polymorphisms provide relative protection against PTB. Additional studies on larger populations with different ethnicities are required to verify our findings.

Rainbow trout fillet biopreservation by edible chitosan-based coating containing egg yolk antibody (IgY) and lycopene.

The aim of the study was to investigate the effect of the extracted egg yolk antibody along with lycopene on the chemical quality of the rainbow trout fillet during 16 days of refrigeration storage. Chickens were immunized against Pseudomonas fluorescens (P. fluorescens), Shewanella putrefaciens (S. putrefaciens) and total spoilage bacteria and their eggs were collected for the isolation of egg yolk antibodies. Then fish fillets were immersed in chitosan-based coating solutions, containing lycopene and extracted antibodies, and analyzed for lipid oxidation changes (peroxide, thiobarbituric acid, free fatty acid and fatty acid profile), physico-chemical properties (pH and water holding capacity), and sensory evaluation, during 16 days of refrigeration storage. Results showed that chitosan solutions with lycopene or IgY could significantly (p < 0.05) increase the oxidative stability of lipids in fish fillets; although, combinational use of lycopene and IgY showed a higher effect on delaying the rate of lipid oxidation. Significant differences were also observed between treatments contained combination of chitosan, antibody and lycopene with the control group, regarding pH and WHC. Saturated fatty acids increased in all treatments, although the changes in the treatments containing lycopene and antibody were significantly (p < 0.05) lower than the control group. Hence the addition of egg yolk antibody and lycopene in coating solution are good bio-preservatives for seafood products as it improves sensory attributes and prevents lipid oxidation.

Alendronate slows down aortic stenosis progression in osteoporotic patients: An observational prospective study.

BACKGROUND: Aortic stenosis (AS) is the most common primary valvular disease. Currently, there is no pharmacological approach for the medical management of AS. We investigated the effect of osteoporosis therapy with alendronate on hemodynamic progression in patients concurrently affected by AS and osteoporosis. MATERIALS AND METHODS: In this observational prospective study, we enrolled 37 women more than 60 years old with diagnosis of AS and concurrent osteoporosis from August 2017 to December 2019. These patients were treated with alendronate 70 mg every week added to their routine treatment for AS, and their outcomes were compared with 33 patients only affected by AS. Echocardiographic changes and N-terminal-prohormone of brain natriuretic peptide (NT-pro-BNP) level were evaluated during about 2 years of follow-up. RESULTS: The mean follow-up time for the treated and nontreated groups was 20.89 ± 2.73 and 20.84 ± 2.76 months, respectively. Mean gradient (P = 0.02) and peak gradient (P = 0.04) of aortic valve were significantly different between the groups after follow-up. Aortic valve area was decreased 0.09 cm2 in the treated group by alendronate and 0.23 cm2 in the other group (P = 0.001). Furthermore, NT-pro-BNP was significantly decreased in patients treated by alendronate (P = 0.01), but it was increased in nontreated patients (P = 0.04). CONCLUSION: Treatment with alendronate in patients with AS and concurrent osteoporosis slows down the progression of stenosis and improves their prognosis. This study could open a new pathway for the treatment of AS. Further studies, particularly randomized controlled clinical trial, should be done for providing more evidence.

Association between CASP3 polymorphisms and overall cancer risk: A meta-analysis of case-control studies.

Several studies inspected the relationship between caspase-3 (CASP3) polymorphisms and the risk of several human cancers, but the findings remain controversial. We conducted a meta-analysis aiming to inspect the association between CASP3 rs1049216 T>C, rs12108497 C>T, rs4647603 G>A, rs4647602 C>A, rs6948 T>G, rs2705897 A>C, and rs113420705 G>A polymorphisms and cancer risk. Eligible studies were recognized by searching the Web of Science, PubMed, Scopus, and Google Scholar databases. Pooled odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to quantitatively evaluate the association between each polymorphism of CASP3 and cancer risk. The rs4647603 variant significantly increased the risk of cancer in an overdominant (OR, 1.44; 95% CI, 1.03-2.01; P = 0.03; AG vs AA+GG) inheritance model. Regarding the rs4647602 variant, the findings revealed that this variant was associated with protection against cancer in homozygous codominant (OR, 0.67; 95% CI, 0.56-0.80; P < 0.00001; AA vs CC), dominant (OR, 0.84; 95% CI, 0.73-0.96; P = 0.009; AC+AA vs CC), recessive (OR, 0.70; 95% CI, 0.61-0.79; P < 0.00001; AA vs AC+CC), and allele (OR, 0.81; 95% CI, 0.75-0.88; P = 0.00001; A vs C) models. The findings suggested that the rs2705897 variant significantly decreased the risk of cancer in heterozygous codominant (OR, 0.80; 95% CI, 0.67-0.94; P = 0.009; AC vs AA), dominant (OR, 0.81; 95% CI, 0.69-0.95; P = 0.009; AC+CC vs AA), overdominant (OR, 0.80; 95% CI, 0.68-0.95; P = 0.01; AC vs CC+AA), and allele (OR, 0.85; 95% CI, 0.74-0.97; P = 0.02; C vs A) models. The results did not support an association between CASP3 rs1049216 and rs6948 polymorphisms and cancer risk. In summary, the findings of this meta-analysis support an association between CASP3 polymorphisms and cancer risk. Larger and well-designed studies are desired to evaluate these associations in detail.

Association between miR-34b/c rs4938723 polymorphism and risk of cancer: An updated meta-analysis of 27 case-control studies.

Several studies investigated the association between miR-34b/c rs4938723 polymorphism and the risk of several human cancers, but the findings remain inconclusive. To evaluate the impact of miR-34b/c rs4938723 on cancer risk, we performed a meta-analysis on all available studies including 12 361 cancer cases and 14 270 controls. Eligible studies were identified by searching PubMed, Web of Science, Scopus, and Google scholar databases. Pooled odds ratios with 95% confidence intervals were calculated in codominant, dominant, recessive, overdominant, and allele models to quantitatively estimate the association. The overall findings showed no significant association between miR-34b/c rs4938723 polymorphism and cancer risk in codominant, dominant, recessive, overdominant, and allele inheritance model. However, in stratified analysis by cancer types, the rs4938723 polymorphism significantly increased the risk of gastrointestinal cancer, hepatocellular carcinoma. In addition, the rs4938723 polymorphism was associated with decreased risk of esophageal squamous cell carcinoma, colorectal cancer, and acute lymphoblastic leukemia. The findings did not support an association between rs4938723 variant and digestive tract as well as gastric cancer. In summary, the findings of this meta-analysis indicated that the miR-34b/c rs4938723 polymorphism might be associated with some cancer development. Larger and well-designed studies are necessary to estimate this association in detail.

Association between the flap endonuclease 1 gene polymorphisms and cancer susceptibility: An updated meta-analysis.

Flap endonuclease 1 (FEN1) has emerged as an important enzyme in the maintenance of genomic instability and preventing carcinogenesis. The relationship between FEN1 -69G>A (rs174538)+4150G>T (rs4246215) polymorphisms and cancer susceptibility has been reported; however, results were inconclusive. In the present study, a meta-analysis of data from eligible reports was carried out to summarize the possible relationship between FEN1 polymorphisms and cancer risk. A total of 11 articles, including 20 studies with 7366 cases and 9028 controls and 18 studies with 6649 cases and 8325 controls for FEN1 rs174538 and FEN1 rs4246215 polymorphisms, respectively, were recruited for meta-analysis. Overall, meta-analyses showed that FEN1 rs174538 and rs4246215 polymorphisms are significantly associated with the decreased risk of cancer. The stratified analysis proposed that both variants were associated with protection against gastrointestinal cancer, breast cancer, hepatocellular cancer, esophageal cancer, gastric cancer, colorectal cancer, and lung cancer. In conclusion, this meta-analysis revealed an association between FEN1 polymorphisms and cancer risk. Additional studies in a larger study population that include subjects from a variety of ethnicities are warranted to further verify our findings.

Association of single nucleotide polymorphisms in TPM1 rs11071720, rs3803499, rs12148828, and rs1972041 with the risk of nonsyndromic cleft lip with or without cleft palate in a sample of the Iranian population, a preliminary report.

Several lines of evidence support an association between tropomyosin 1 (TPM1) and the risk of nonsyndromic cleft lip with or without cleft palate (NSCL/P). The present study aimed to investigate the association between TPM1 polymorphisms and the risk of NSCL/P in an Iranian population. This case-control was done on 105 NSCL/P patients and 110 unrelated healthy controls. TPM1 rs11071720, rs3803499, rs12148828, and rs1972041 polymorphisms were genotyped by the polymerase chain reaction-restriction fragment length polymorphism method. The finding showed that rs11071720 polymorphism significantly increased the risk of NSCL/P in homozygous codominant (odds ratio [OR] = 2.54, 95% confidence interval [CI] = 1.14-5.69, p = 0.023, TT vs. CC), recessive (OR = 2.33, 95% CI = 1.06-5.18, p = 0.021, TT vs. CT + CC), and allele (OR = 1.53, 95% CI = 1.02-2.30, p = 0.030, T vs. C). The rs12148828 polymorphism was associated with protection against NSCL/P in codominant (OR = 0.27, 95% CI = 0.15-0.48, p < 0.001, TC vs. TT) and allele (OR = 0.38, 95% CI = 0.22-0.64, p < 0.001, C vs. T). Regarding rs3803499, the findings proposed that this polymorphism significantly increased the risk of NSCL/P in codominant (OR = 3.86, 95% CI = 1.19-12.56, p = 0.025, CC vs. TT) and recessive (OR = 3.74, 95% CI = 1.09-14.15, p = 0.018, CC vs. CT + TT). No significant association was practical between rs1972041 polymorphism and NSCL/P. In conclusion, the findings proposed that TPM1 polymorphisms may contribute to the etiology of NSCL/P in a sample of the Iranian population.

Mutations in the Histone Modifier PRDM6 Are Associated with Isolated Nonsyndromic Patent Ductus Arteriosus.

Nonsyndromic patent ductus arteriosus (PDA) is a common congenital heart defect (CHD) with both inherited and acquired causes, but the disease mechanisms have remained elusive. Using combined genome-wide linkage analysis and whole-exome sequencing (WES), we identified independent mutations in PRDM6, which encodes a nuclear protein that is specific to vascular smooth muscle cells (VSMC), has histone methyl transferase activities, and acts as a transcriptional suppressor of contractile proteins. In vitro assays showed that the mutations cause loss of function either by intracellular redistribution of the protein and/or by alteration of its methyltransferase activities. Wild-type embryonic ductus arteriosus (DA) exhibited high levels of PRDM6, which rapidly declined postnatally as the number of VSMCs necessary for ductus contraction increased. This dynamic change suggests that PRDM6 plays a key role in maintaining VSMCs in an undifferentiated stage in order to promote their proliferation and that its loss of activity results in premature differentiation and impaired remodeling of the DA. Our findings identify PRDM6 mutations as underlying genetic causes of nonsyndromic isolated PDA in humans and implicates the wild-type protein in epigenetic regulation of ductus remodeling.