Genetic association of Interleukin-17A polymorphism in Bangladeshi patients with breast and cervical cancer: a case-control study with functional analysis.

BACKGROUND: Breast and cervical cancer are the two leading cancers in terms of incidence and mortality. Previous studies reported different interleukins, including interleukin-17A (IL-17A) to be responsible for the development and progression of these malignancies. Therefore, we speculated that the variants in this gene might be associated with these cancer developments in Bangladeshi population. For evaluating the hypothesis, we investigated the association of IL-17A rs3748067 polymorphism with the susceptibility of both breast and cervical cancer. METHODS: This case-control study was performed on 156 breast cancer patients, 156 cervical cancer patients, and 156 controls using the tetra-primer amplification refractory mutation system-polymerase chain reaction. The statistical software package SPSS (version 25.0) was applied for analyses. The genetic association was measured by the odds ratio (OR) and 95% confidence intervals (CIs). A statistically significant association was considered when p-value ≤ 0.05. Functional analysis was performed using GEPIA and UALCAN databases. RESULTS: From the calculation of the association of IL-17A rs3748067 with breast cancer, it is found that no genotype or allele showed a statistically significant association (p>0.05). On the other hand, the analysis of IL-17A rs3748067 with cervical cancer demonstrated that CT genotype showed a significant association (CT vs. CC: OR=1.79, p=0.021). In the overdominant model, CT genotype also revealed a statistically significant association with cervical cancer, which is found to be statistically significant (OR=1.84, p=0.015). CONCLUSION: Our study summarizes that rs3748067 polymorphism in the IL-17A gene may be associated with cervical cancer but not breast cancer in Bangladeshi patients. However, we suggest studies in the future with a larger sample size.

Assessment of the association of CYP1A1 gene polymorphisms with the susceptibility of cervical cancer: A case-control study and meta-analysis.

Background: Cervical cancer (CC) is the second most common type of female malignancy in Bangladesh. Polymorphisms in the CYP1A1 gene have been reported to be associated with CC in different populations. This case-control study with meta-analysis was undertaken to assess the relation of CYP1A1 rs4646903 and rs1048943 polymorphisms with the susceptibility of CC. Methods: A total of 185 CC patients and 220 controls were recruited, and the PCR-RFLP (Polymerase chain reaction-restriction fragment length polymorphism) technique was applied for genotyping. Again, 42 eligible studies (24 with rs4646903 and 18 with rs1048943) were included for meta-analysis, and RevMan 5.3 and the MetaGenyo web-based tool were used. Results: The rs4646903 polymorphism was significantly linked with CC in all association models, namely, additive 1, additive 2, dominant, recessive, overdominant, and allele models (OR = 2.41, 4.75, 2.67, 3.61, 2.13, and 2.44 with corresponding 95% CI = 1.55-3.76, 1.81-12.45, 1.75-4.07, 1.39-9.35, 1.38-3.30, and 1.71-3.48, respectively). On the contrary, rs1048943 showed no association (p > 0.05) with CC. Haplotype analysis revealed AT and AC haplotypes significantly decreased (OR = 0.45) and increased (OR = 4.86) CC risk, respectively, and SNPs are in strong linkage disequilibrium (D' = 0.912, r2 = 0.448). Again, rs4646903 carriers with a contraception history and >5 years of taking contraceptives showed an enhanced risk of CC (OR = 2.39, OR = 3.05). Besides, rs1048943 carriers aged >40 years (OR = 0.44), conceived first child aged ≤18 years (OR = 3.45), and history of contraceptives (OR = 2.18) were significantly linked with CC. Our meta-analysis found that for CYP1A1 rs4646903 codominant 1 (COD 1), codominant 2 (COD 2), codominant 3 (COD 3), dominant model (DM), recessive model (RM), and allele model (AM) in Caucasians and overdominant model (OD) in the overall population are associated with an elevated risk of CC, whereas rs1048943 is also associated with CC in overall, Caucasians and Asians in some genetic models. Conclusion: Our case-control study and meta-analysis summarize that CYP1A1 rs4646903 and rs1048943 polymorphisms may be correlated with cervical cancer.

A comprehensive review on clinically proven medicinal plants in the treatment of overweight and obesity, with mechanistic insights.

Background and objectives: Obesity has become a global health issue, more precisely, a pandemic throughout the present world due to its high prevalence in the recent era. Increased risk of morbidity and mortality in obese patients can be attributed to its association with the development of different life-threatening conditions. Plants are considered one of the most important sources of bioactive molecules which are used against a wide range of health disorders. This systematic review explores the efficacy as well as the safety profile of commonly used medicinal plants in the management of obesity that may help people to maintain a healthy weight. Methods: This review is based on comprehensive literature searches from PubMed, Science Direct, Scopus, and Google Scholar databases using the keywords- "plants in obesity", "plants used in weight reduction" or keywords that are similar to those. Medicinal plants which have been clinically proven for their anti-obesity effect have only been selected for this study and attempts to investigate beneficial effects and adverse effects along with their mechanism of action have also been taken in this review. Results: A significant reduction of weight in both human and other animals are exhibited by the extracts of Phaseolus vulgaris, green coffee, Yerba Mate, green tea, Gynostemma pentaphyllum, and the combination of Cissus quadrangularis/Irvingia gabonensis. All of those plant extracts seemed to work on different physiological pathways and none of those extracts showed any notable adverse effects in human or animal models. Conclusion: Our review suggests that the discussed medicinal plants are effective in reducing the weight of obese patients without causing notable adverse reactions. Although further study is necessary to confirm their exact molecular mechanism and safety in human use.

The protective role of vitamin C in the management of COVID-19: A Review.

BACKGROUND: The outbreak of coronavirus infectious disease-2019 (COVID-19) is globally deemed a significant threat to human life. Researchers are searching for prevention strategies, mitigation interventions, and potential therapeutics that may reduce the infection's severity. One such means that is highly being talked in online and in social media is vitamin C. MAIN TEXT: Vitamin C is a robust antioxidant that boosts the immune system of the human body. It helps in normal neutrophil function, scavenging of oxidative species, regeneration of vitamin E, modulation of signaling pathways, activation of pro-inflammatory transcription factors, activation of the signaling cascade, regulation of inflammatory mediators, and phagocytosis and increases neutrophil motility to the site of infection. All of these immunological functions are required for the prevention of COVID-19 infection. CONCLUSION: Considering the role of vitamin C, it would be imperative to administrate vitamin C for the management of severe COVID-19. However, there is no specific clinical data available to confirm the use of vitamin C in the current pandemic.

Risk of type 2 diabetes mellitus and cardiovascular complications in KCNJ11, HHEX and SLC30A8 genetic polymorphisms carriers: A case-control study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD) are two deadly diseases caused by the complex interaction of multiple genetic loci, lifestyle and environmental factors. Genome-wide association studies described hundreds of susceptibility loci for T2DM and T2DM-related CVD, but it remains uncertain due to geographic and ethnic variations. The objective of this study was to evaluate the associations of KCNJ11 rs5219, SLC30A8 rs13266634 and HHEX rs1111875 polymorphisms with T2DM and related CVD. METHODS: Genotyping of all three polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method on 250 T2DM cases and 246 healthy controls. Both descriptive and inferential statistical methods were applied using MedCalc and IBM SPSS software programs for statistical analyses. RESULTS: A significantly increased association of KCNJ11 rs5219 (p<0.05) with T2DM was found in dominant, recessive, heterozygote, homozygote, and allele model (aOR = 2.23, 2.03, 1.90, 3.09, and 1.80, respectively). For SLC30A8 rs13266634, only dominant, heterozygote, and allele model (aOR = 3.37, 3.59, and 1.79, respectively) showed significantly increased association with T2DM. SNP rs1111875 (HHEX) also revealed 2.08, 4.18, 5.93, and 2.08-times significant association in dominant, recessive, homozygote, and allele models. Besides, a significantly reduced correlation of KCNJ11 rs5219 was found with T2DM-related CVD in the recessive and allele model (aOR = 0.40 and 0.65, respectively). Again, a significant difference was observed between T2DM-related CVD and non-CVD patients in terms of gender distribution, fasting blood glucose (FBG), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), and triglycerides (TG). CONCLUSIONS: Our investigation indicates that KCNJ11 rs5219, SLC30A8 rs13266634 and HHEX rs1111875 polymorphisms are associated with T2DM. Moreover, KCNJ11 rs5219 polymorphism is correlated with the risk of T2DM-related CVD.

CNTNAP2 gene polymorphisms in autism spectrum disorder and language impairment among Bangladeshi children: a case-control study combined with a meta-analysis.

Autism spectrum disorder (ASD) is a multifactorial neurodevelopmental disorder characterized by communication deficits, impaired social interactions, repetitive and stereotyped behaviors with restricted interests, and connected with the interaction between environmental factors and genetic vulnerability. CNTNAP2 gene has been extensively investigated for ASD and related neurodevelopment diseases. However, previous studies have resulted in an inconsistent outcome. Based on this fact, we conducted a case-control study followed by a meta-analysis to investigate the association of rs7794745 and rs2710102 polymorphisms with ASD. A total of 216 autistic children and 240 healthy volunteers were recruited, and genotyping was performed using the PCR-RFLP method. We observed that SNP rs7794745 revealed a significantly (p < 0.05) increased association with the development of ASD in children in all genetic models. No significant association was found for rs2710102 with ASD. Besides, rs2710102 exhibited a significant association with language impairment in TC genotype, C allele, and dominant model. From the meta-analysis of both SNPs, we found a significant association in codominant 1, 2, and the dominant model of rs2710102 and codominant 1 and dominant model of rs7794745 with ASD. Our case-control study suggests that rs7794745 polymorphism is associated with ASD, while rs2710102 is correlated with language impairment. Moreover, meta-analysis results indicated the association between both rs7794745 and rs2710102 polymorphisms and ASD.

Polymorphic variants INSIG2 rs6726538, HLA-DRB1 rs9272143, and GCNT1P5 rs7780883 contribute to the susceptibility of cervical cancer in the Bangladeshi women.

OBJECTIVE: Cervical cancer is a gynecological health problem, affecting nearly 500,000 women each year worldwide. Genome-wide association studies have revealed multiple susceptible genes and their polymorphisms for cervical carcinoma risk. We have carried out this case-control study to investigate the association of INSIG2 rs6726538 (A; T), HLA-DRB1 rs9272143 (T; C), and GCNT1P5 rs7780883 (G; A) with cervical cancer. METHODS: The present study recruited 234 cervical cancer patients as cases and 212 healthy females as controls. We have applied the tetra-primer amplification refractory mutation system polymerase chain reaction (T-ARMS-PCR) method for genotyping. RESULTS: The SNP rs6726538 was significantly associated with increased risk of cervical cancer in all genetic models (AT vs. AA: OR = 3.30, 95% CI = 2.19-4.97, p < 0.0001; TT vs. AA: OR = 8.72, 95% CI = 3.87-19.7, p < 0.0001; AT+TT vs. AA: OR = 3.87, 95% CI = 2.61-5.73, p < 0.0001; T vs. A: OR = 2.97, 95% CI = 2.20-4.01, p < 0.0001) except the recessive model which showed a significantly reduced risk (TT vs. AA+AT: OR = 0.20, 95% CI = 0.09-0.44, p = 0.0001). rs9272143 showed significantly reduced risk for the additive model 1, dominant model, and allelic model (TC vs. TT: OR = 0.46, 95% CI = 0.31-0.70, p = 0.0004; TC+CC vs. TT: OR = 0.47 95% CI = 0.32-0.70, p = 0.0002; C vs. T: OR = 0.56, 95% CI = 0.40-0.78, p = 0.0006, respectively). The third variant, rs7780883, was significantly associated with increased risk in additive model 2, dominant, and allelic models (AA vs. GG: OR = 5.08, 95% CI = 2.45-10.5, p < 0.0001; GA+AA vs. GG: OR = 1.54, 95% CI = 1.06-2.24, p = 0.0237; A vs. G: OR = 1.88, 95% CI = 1.34-2.52, p < 0.0001, consecutively), whereas recessive model reduced the risk of cervical cancer (AA vs. GG+GA: OR = 0.20, 95% CI = 0.09-0.41, p < 0.0001). Other models of these SNPs were not associated with cervical cancer. All significant associations for three SNPs withstand after Bonferroni correction except the additive model 2 of rs7780883. CONCLUSION: Our study concludes that INSIG2 rs6726538, HLA-DRB1 rs9272143, and GCNT1P5 rs7780883 polymorphisms may contribute to the development of cervical cancer in the Bangladeshi population.

Detection of association of IL1ß, IL4R, and IL6 gene polymorphisms with cervical cancer in the Bangladeshi women by tetra-primer ARMS-PCR method.

BACKGROUND: Cervical cancer (CC) is the main cause of cancer-related deaths among women in developing countries. It is the second leading female malignancy in Bangladesh in terms of incidence and mortality. Our present study aimed to investigate the association of IL1ß (rs16944), IL4R (rs1801275), and IL6 (rs1800797) gene polymorphisms with the susceptibility of cervical cancer. MATERIALS AND METHODS: This case-control study was conducted on 252 cervical cancer patients and 228 healthy volunteers, using tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR). RESULTS: In the case of rs16944 polymorphism, GG genotype (OR = 2.10, 95%CI = 1.24-3.56), dominant model (OR = 1.71, 95% CI = 1.11-2.63), recessive model (OR = 1.54, 95% CI = 1.01-2.35), and G allele (OR = 1.30, 95% CI = 1.005-1.68) were significantly associated with increased cervical cancer risk. Among these, GG genotype and dominant model remained significant after the Bonferroni correction (p < 0.017). For rs1801275 polymorphism, GG genotype (OR = 2.66, 95% CI = 1.49-4.75), dominant model (OR = 1.49, 95% CI = 1.04-2.14), recessive model (OR = 2.45, 95% CI = 1.40-4.27), and G allele (OR = 1.59, 95% CI = 1.21-2.10) significantly elevated the risk of cervical cancer but significance did not exist for dominant model after the Bonferroni correction. rs1800797 variant showed significantly increased risk in all genetic models including, AG genotype (OR = 8.13, 95% CI = 5.27-12.55), AA genotype (OR = 9.86, 95% CI = 2.76-35.21), dominant model (OR = 8.25, 95% CI = 5.40-12.60), recessive model (OR = 4.41, 95% CI = 1.25-15.56), and A allele (OR = 4.99, 95% CI = 3.49-7.13) and the significances were consistent with the Bonferroni correction except recessive model. Haplotyping analysis indicates that GAA (p = 5.15x10-5) and GAG haplotypes (p = 4.72x10-9) significantly decreased the risk of CC, whereas AAA (p = 3.89x10-9), AAG (p = 0.0003), AGA (p = 3.98x10-5) and AGG haplotypes (p = 0.002) significantly increased the risk of CC. The IL1ß mRNA level was up-regulated, which was associated with poor prognosis in silico. CONCLUSION: Our results conclude that rs16944 (IL1ß), rs1801275 (IL4R), and rs1800797 (IL6) polymorphisms are associated with cervical cancer in Bangladeshi women.

Genetic Polymorphism of miR-218-2 (rs11134527) in Cervical Cancer: A Case-Control Study on the Bangladeshi Women.

BACKGROUND: The prevalence of Cervical Cancer (CC) is disproportionately higher in developing countries. It is the second most frequent cancer type among Bangladeshi women and the major cause of morbidity and mortality. However, no previous data reported the association of miR-218-2 gene polymorphisms in Bangladeshi cervical cancer patients. AIM: This case-control study was designed to find the link between the rs11134527 polymorphism in miR-218-2 and CC. METHODS: A total of 488 subjects were recruited, comprising 256 cervical cancer patients and 232 healthy females. Genotyping was conducted with the tetra-primer ARMS-PCR technique to detect the association. RESULTS: The results of genotype data showed that rs11134527 was in the Hardy-Weinberg equilibrium in both CC cases and controls (P >0.05). Overall, the polymorphism was found to be significantly associated with an increased risk of cervical cancer with AG genotype (AG vs. GG: OR = 2.26, 95% Cl = 1.40-3.66, P = 0.0008), AA genotype (AA vs. GG: OR = 3.64, 95% Cl = 2.17-6.10, P <0.0001), dominant model (AG+AA vs. GG: OR = 2.75, 95% Cl = 1.75-4.31, P <0.0001), recessive model (AA vs. GG+AG: OR = 2.08, 95% Cl = 1.41-3.08, P = 0.0002), and A allele (A vs. G: OR = 1.94, 95% Cl = 1.51-2.51, P <0.0001). All of these correlations remained statistically significant after performing Bonferroni correction (P <0.008). CONCLUSION: Our study suggests that the rs11134527 polymorphism in the miR-218-2 gene contributes to the susceptibility of CC in Bangladeshi women.

A clinical evaluation of the alterations in the level of serum zinc, copper, iron, and manganese in the ischemic heart disease patients of Bangladesh - A case-control study.

BACKGROUND: Ischemic heart disease (IHD) is a major cause of death globally. Countries vary in their rates, and changes have occurred over time. Nowadays, developing countries pose new public health challenges. OBJECTIVES: The objective of the present study was to appraise the alterations in the levels of serum Zn, Cu, Fe, and Mn that occur in patients with ischemic heart disease and to depict the correlations of the effects of these changes that lead to the pathogenesis of IHD. METHODS: Zn, Cu, Fe, and Mn in the IHD patients were determined by Atomic Absorption Spectroscopy (AAS). RESULTS: This study evaluated 52 patients with IHD, and 61 healthy volunteers served as controls. The primary outcomes of interest were explored regarding the correlations of the serum levels of these trace elements in patients with IHD. The secondary outcomes were explored in terms of inter-element relations to connect them with the pathogenesis of IHD. Our study found significantly reduced levels of Zn and Cu (2.50 ± 0.19 mg/L and 2.52 ± 0.17 mg/L, respectively) and an elevated level of Fe (148.97 ± 17.25 mg/L) in the patient group with IHD. The level of Mn (7.32 ± 1.23 mg/L) was elevated in the sera of the patients with ischemic heart disease (IHD) compared to healthy control subjects. CONCLUSION: Our results indicate strong associations of the pathogenesis of IHD with depleted serum levels of Zn and Cu and elevated Fe and Mn levels, which may provide a prognostic tool for the treatment of this concerning the disease.

Association of DRD2 gene polymorphisms with schizophrenia in the young Bangladeshi population: A pilot study.

PURPOSE: DRD2 gene is considered one of the most important candidate genes for the schizophrenia (SCZ) development due to its role in dopamine signaling and no genetic association study has been conducted yet on the Bangladeshi SCZ patients. The objective of the present study was to investigate the association of DRD2 genetic polymorphisms (rs4648317, rs4936270, and rs7131056) with SCZ in the Bangladeshi population. PATIENTS AND METHODS: This case-control study consisted of 101 SCZ patients and 101 controls. Genotyping was performed by the polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The average ages were 22.15 and 22.09 years in patients and controls, respectively (p > 0.05). CT genotype of rs4936270 showed a significantly higher risk for the development of SCZ compared to CC genotype (OR = 2.0, p = 0.023), whereas no association was found for TT genotype. For the dominant model and T allele, rs4936270 showed a higher risk for the development of SCZ (OR = 2.01, p = 0.020; OR = 1.76, p = 0.021, respectively), while the recessive model had no association with SCZ. A statistically significant (OR = 2.70, p = 0.036) higher risk was found for the AA genotype, but no association was found for GA genotype of rs4648317 SNP compared to GG genotype. In case of dominant and recessive models, rs4648317 showed no association with SCZ. 'A' allele of rs4648317 SNP was found to be significantly associated with the elevated risk of SCZ (OR = 1.50, p = 0.044). No association with SCZ of rs7131056 SNP was found for AC, CC genotypes, dominant, recessive, and allele models. Furthermore, from the haplotyping analysis, we found that CAA and TAA haplotypes of rs4936270, rs7131056 and rs4648317 SNPs are associated with SCZ (χ2 = 8.26, p = 0.004; χ2 = 5.31, p = 0.021, respectively). After Bonferroni correction, the association of SCZ did not withstand with any genotype, allele and haplotype (p < 0.017) except CAA haplotype. CONCLUSION: Our results suggest that DRD2 gene polymorphisms may be associated with the susceptibility of SCZ in the young Bangladeshi population.

How the association between obesity and inflammation may lead to insulin resistance and cancer.

BACKGROUND AND OBJECTIVES: Obesity is associated with metabolic dysfunction and over nutrition. Increased body mass index and obesity are strongly amalgamated with changes in the physiological function of adipose tissue, leading to altered secretion of adipocytokines, inflammatory mediators release as well as chronic inflammation and insulin resistance. The purposes of this study were to review the evidence of how obesity and inflammation may lead to insulin resistance and cancer. SUMMARY: Recent findings suggested that increased level of inflammatory mediators in obesity, plays an introductory and cabalistic role in the development of different types of inflammatory disorders including type 2 diabetes mellitus. Link between elevated body mass index and type 2 diabetes mellitus (T2DM). Several of the factors-such as increased levels of leptin, plasminogen activator inhibitor-1, decreased levels of adiponectin, insulin resistance, chronic inflammation etc. consequently result in carcinogenesis and carcinogenic progression too. CONCLUSION: This review summarizes how cytokine production in adipose tissue of obese subject creates a chronic inflammatory environment that favors tumor cell motility and invasion to enhance the metastatic potential of tumor cells. High levels of cytokine in the circulation of affected individuals have been associated with a significantly worse outcome. This article also reconnoiters the mechanisms that link obesity to numerous disorders such as inflammation, diabetes, cancers and most specifically combine these processes in a single image. Understanding these mechanisms may assist to understand the consequences of obesity.

Ascertainment of pharmacological activities of Allamanda neriifolia Hook and Aegialitis rotundifolia Roxb used in Bangladesh: An in vitro study.

The present study was cherished to investigate in vitro thrombolytic, membrane stabilizing and antibacterial activities of Allamanda neriifolia and Aegialitis rotundifolia. Different types methanolic extracts of these two medicinal plants were tested for determining membrane stabilizing activity at a hypotonic solution and heat induce condition by comparing with reference standard acetyl salicylic acid (0.10 mg/mL), where thrombolytic activity assessment was done by employing Streptokinase as standard drug. Finally, antibacterial activity was performed against Staphylococcus aureus as a Gram-positive (+ve) and Salmonella typhi, Escherichia coli and Pseudomonas aeruginosa as Gram negative (-ve) bacteria by using disc diffusion method. In case of membrane stabilizing studies, crude methanolic extracts of A. neriifolia at 10 mg/ml concentration, more importantly, showed 45.80% & 23.52% whereas 10 mg/ml concentration of A. rotundifolia more significantly (p < 0.01) produced 38.40% and 27.04% inhibition of hemolysis for both experimental conditions. Dose-dependently increased activity was found in the thrombolytic study where 10 mg/ml concentration of both A. neriifolia and A. rotundifolia more significantly (p < 0.01) showed 41.91% and 32.76% lysis of clot respectively by in vitro clot lysis assay method. Crude methanolic extracts of A. rotundifolia did not show any suitable antibacterial property against the test bacteria. However, the gram positive (+ve) bacteria also seemed resistant against A. neriifolia extract but this crude methanolic extracts was found to generate moderate antibacterial action against gram-negative (-ve) bacteria. The obtained results confirmed the presence of thrombolytic, membrane stabilizing activity for both plant extract along with moderate antibacterial activity for A. neriifolia.