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.

The linkage between IL-6 rs1800797 variant and breast cancer susceptibility in Bangladeshi women: A case-control study.

Background and Aims: Breast cancer is one of the deadliest diseases affecting women in Bangladesh, and its prevalence is increasing year by year. Although several IL-6 single nucleotide polymorphisms have been implicated in BC susceptibility and prognosis in various studies, no research has been done to investigate the relationship between breast cancer and IL-6 in Bangladeshi women. This investigation aimed to explore the linkage between the rs1800797 variant of IL-6 and the susceptibility to breast carcinoma among women in Bangladesh. Methods: The IL-6 rs1800797 variant was genotyped in 218 subjects (110 cases and 108 controls) using the tetra-primer ARMS-PCR method. The statistical analysis was applied utilizing the SPSS software version 24.0. UALCAN database was used for IL-6 mRNA analysis, and genotype-based gene expression was retrieved from GTEx Portal. Results: This study found a significant link between IL-6 rs1800797 variants and increased chance of breast cancer across different genetic inheritance models, including additive model 1 (AG vs. GG: OR = 2.16, p = 0.035); dominant model (AG + AA vs. GG: OR = 2.26, p < 0.05); overdominant model (AG vs. GG + AA: OR = 2.08, p < 0.05); and allelic model (A vs. G: OR = 2.15, p < 0.05). However, an insignificant association of breast cancer was found in both additive model 2 (AA vs. GG: OR = 2.91, p > 0.05) and the recessive model (AA vs. GG + AG: OR = 2.52, p > 0.05). Under the analysis of the probability of false positive reports, no significant values were found in different models when the OR was 1.5, and the prior probability was 0.25. Conclusions: A significant relationship was found between the IL-6 rs1800797 genetic variant and the risk of breast cancer. However, the findings of the study should be further investigated with a larger sample size to validate the correlation.

MMP-3 -1171 5A/6A promoter polymorphism and cancer susceptibility: an updated meta-analysis and trial sequential analysis.

Purpose: Previous studies of MMP-3 -1171 5A/6A in cancers have produced inconclusive outcomes. This updated meta-analysis was performed to clarify the link between this variant and cancer. Methods: Databases including PubMed, Google Scholar, EMBASE and Cochrane were searched for data collection. The associations were calculated by odds ratios with 95% CIs. Results: 63 eligible studies with 14,252 cases and 15,176 controls were included. The codominant 2, codominant 3, dominant, recessive and allele models were found to be significantly associated with 1.28-, 1.13-, 1.13-, 1.19- and 1.13-fold enhanced overall risk of cancer, respectively. Stratification analysis revealed a 1.28-times enhanced risk of esophageal cancer (codominant 1), 1.29- and 1.26-fold (codominant 3) and 1.18- and 1.28-fold (recessive model) enhanced risk in colorectal and gastrointestinal cancers, respectively, 1.30-, 1.35- and 1.22-times in codominant model 1, dominant and allele models for breast cancer, 1.56-fold (codominant 2) for gynecological cancer and 2.40-times in codominant model 2 for hepatocellular cancer. Conclusion: This meta-analysis suggests a significant association between the MMP-3 -1171 5A/6A variant and cancer. This meta-analysis was registered at INPLASY (registration number: INPLASY202280049).

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.

Evaluation of the Association between FGFR2 Gene Polymorphisms and Breast Cancer Risk in the Bangladeshi Population.

Breast cancer is considered the most frequent cause of mortality from malignancy among females. Fibroblast growth factor receptor 2 (FGFR2) gene polymorphisms are highly related to the risk of breast cancer. However, no investigation has been carried out to determine the association of FGFR2 gene polymorphisms in the Bangladeshi population. Based on polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), this study was performed to evaluate the association of FGFR2 (rs1219648, rs2420946, and rs2981582) variants in 446 Bangladeshi women (226 cases and 220 controls). A significant association of the FGFR2 rs1219648 variant with breast malignancy was reported in additive model 1 (aOR = 2.87, p < 0.0001), additive model 2 (aOR = 5.62, p < 0.0001), the dominant model (aOR = 2.87, p < 0.0001), the recessive model (aOR = 4.04, p < 0.0001), and the allelic model (OR = 2.16, p < 0.0001). This investigation also explored the significant association of the rs2981582 variant with the risk of breast cancer in additive model 2 (aOR = 2. 60, p = 0.010), the recessive model (aOR = 2.47, p = 0.006), and the allelic model (OR = 1.39, p = 0.016). However, the FGFR2 rs2420946 polymorphism showed no association with breast cancer except in the overdominant model (aOR = 0.62, p = 0.048). Furthermore, GTT (p < 0.0001) haplotypes showed a correlation with breast cancer risk, and all variants showed strong linkage disequilibrium. Moreover, in silico gene expression analysis showed that the FGFR2 level was upregulated in BC tissues compared to healthy tissues. This study confirms the association of FGFR2 polymorphisms with breast cancer risk.

Analysis of serum calcium, sodium, potassium, zinc, and iron in patients with pre-eclampsia in Bangladesh: A case-control study.

Background and Aims: Pre-eclampsia is a particular type of pregnancy condition. Although the primary etiology of pre-eclampsia is unclear, it hypothesizes that the alteration of trace elements and macro-minerals may play a crucial function in the pathogenesis of Pre-eclampsia. Therefore, our research sought to ascertain the serum level of trace elements (zinc, iron) and macro-minerals (sodium, calcium, potassium) and their possible association with pre-eclampsia. Methods: The present study was conducted with 74 pre-eclampsia pregnant women (case) and 118 pregnant women having normal blood pressure (controls). Atomic Absorption Spectroscopy determined the serum level of trace components and electrolytes. Results: The researchers discovered notable differences in maternal age, gestational period, body mass index, systolic and diastolic blood pressure, hemoglobin, and creatinine level. Results of serum analysis revealed that calcium (52.06 ± 3.71 mg/L vs. 65.93 ± 2.57 mg/L, p < 0.05) and potassium (63.44 ± 5.33 mg/L vs. 102.54 ± 4.25 mg/L, p < 0.001) concentrations were substantially lower in the patient group than in control. Serum zinc (0.34 ± 0.02 mg/L vs. 0.52 ± 0.02 mg/L, p < 0.001) and iron (0.38 ± 0.03 mg/L vs. 0.46 ± 0.02 mg/L, p < 0.05) concentration were also considerably decreased in pre-eclampsia participants compared with a pregnant normotensive group. Pearson's correlation research results in the patient group revealed a connection between trace elements or macro minerals. In addition, the systolic blood pressure was positively correlated with sodium (r = 0.392, p < 0.01) and negatively correlated with potassium (r = -0.257, p < 0.05) in the control group. Conclusions: This study concludes that calcium, potassium, iron, and zinc levels were lower, whereas sodium levels were higher in Bangladeshi pre-eclampsia patients compared to controls. These findings with Pearson's correlation and the inter-element relationship between the patient and a control subject results can act as critical indication factors for patients with pre-eclampsia in Bangladesh and, as a result, may require a higher intake of calcium, potassium, iron, and zinc for effective therapeutic intervention and reduce the intake of sodium.

A review on monkeypox virus outbreak: New challenge for world.

Background: Monkeypox is a viral zoonotic disease caused by the monkeypox virus, a double-stranded DNA-enveloped virus that can be transmitted from animal to human or human to human. Consequently, it emerged as the most important orthopoxvirus for public health. Based on available online literature, this study reviewed the majority of the data representing the outbreak, diagnosis, treatment, and prevention of monkeypox. Methods: The literature search was conducted between July 5 and September 15, 2022. In addition to reviewing the databases of World Health Organization (WHO), Centers for Disease Control and Prevention (CDC), Africa CDC, and United Kingdom Health Security Agency monkey pox advice, 43 papers were studied in depth. Results and Discussion: Human monkeypox was first identified in 1970 in a child in the Democratic Republic of the Congo. Until May 6, 2022, it was endemic in West and Central African countries and infrequently occurred outside of Africa. However, many cases have been identified in several nonendemic countries since May 13, 2022, with no prior human or animal travel from endemic areas; that was the first time to document the cases and long-term transmission in countries with no epidemiological ties to endemic African countries. Seven travel-related human monkeypox cases were recorded outside of Africa from September 2018 to November 2021: one in Israel, one in Singapore, and two in the US Youth are most affected. Monkeypox's unanticipated development in places with no known epidemiological linkages raises concerns about the virus's evolution, which permits undetected transmission for a long period. Conclusion: Monkeypox is no longer a rare, self-limiting disease limited to endemic countries. Its ever-changing epidemiology and transmission dynamics have increased the possibility of its evolving into a much deadlier pathogen. Therefore, improved surveillance and detailed case and contact investigation are required to comprehend the ever-changing epidemiology of monkeypox.

TF and TCF4 gene polymorphisms are linked to autism spectrum disorder: a case-control study.

OBJECTIVE: Although the prevalence of autism spectrum disorder (ASD) is increasing, appropriate diagnosis and prevention strategies are still lacking. This case-control study was designed to explore the association between ASD and the rs1867503 and rs9951150 polymorphisms of the TF and TCF4 genes, respectively. METHODS: Ninety-six children with ASD and 118 healthy children were recruited and polymerase chain reaction-restriction fragment length polymorphism technique was applied for genotyping. RESULTS: The frequencies of the mutant allele G were 48% and 44% for the rs1867503 and rs9951150 polymorphisms, respectively. In our analysis, both TF and TCF4 polymorphisms were associated with an increased risk of developing ASD. AG heterozygotes (OR = 3.18), GG mutant homozygotes (OR = 2.62), AG + GG combined genotypes (OR = 2.98), and G mutant alleles of TF rs1867503 (OR = 1.94) were associated with a significantly elevated risk of ASD. Likewise, AG heterozygotes (OR = 2.92), GG mutant homozygotes (OR = 2.36), AG + GG combined genotypes (OR = 2.72), and G minor alleles of TCF4 rs9951150 (OR = 1.92) were associated with a significantly elevated risk of ASD. CONCLUSIONS: Our results indicate that TF rs1867503 and TCF4 rs9951150 polymorphisms may be strongly associated with the development of ASD in Bangladeshi children.

Susceptibility of TNFAIP8, TNFAIP8L1, and TNFAIP2 Gene Polymorphisms on Cancer Risk: A Comprehensive Review and Meta-Analysis of Case-Control Studies.

Objectives: The TNFAIP8 gene family and TNFAIP2 gene are inextricably linked to an elevated risk of cancer development. This systemic review and meta-analysis seeks to establish the relationship between TNFAIP8 (rs11064, rs1045241, rs1045242, and rs3813308), TNFAIP8L1 (rs1060555), and TNFAIP2 (rs710100 and rs8126) polymorphisms with the risk of cancer. Methods and Materials: A systematic search of multiple databases from January 2022 to April 2022 was used to identify relevant studies. Odds ratios (ORs) with corresponding 95% CI and p-value were calculated to assess the association. Bonferroni correction was performed to correct p-values. Trial sequential analysis (TSA) and in-silico messenger RNA expression were also performed. Review Manager 5.4 software was used for performing this meta-analysis. Results: This study comprised 6909 cancer patients and 7087 healthy participants from 14 studies. Four genetic models of rs11064 (codominant 2 [COD2]: OR = 2.30, p = 7.83 × 10-5; codominant 3 [COD3]: OR = 2.10, p = .0006; recessive model [RM]: OR = 2.24, p = .0001; AC: OR = 1.47, p = .037), two genetic models of rs1045241 (codominant 1 [COD1]: OR = 1.27, p = .009; overdominant model [ODM]: OR = 1.24, p = .018), four genetic models of rs1045242 (COD1: OR = 1.52, p = .005; dominant model (DM): OR = 1.56, p = .002; OD: OR = 1.48, p = .008; AC: OR = 1.48, p = .002), and three genetic models of rs8126 (COD2: OR = 1.41, p = .0005; COD3: OR = 1.44, p = .0002; RM: OR = 1.43, p = .0001) were statistically linked to cancer risk. Only one genetic model of rs1060555 polymorphism showed a significant protective association with cancer (COD2: OR = 0.80, p = .048). The outcomes of TSA also validated the findings of the meta-analysis. Conclusion: This study summarizes that rs11064, rs1045241, and rs1045242 polymorphisms of TNFAIP8 gene and rs8126 polymorphism of TNFAIP2 gene are significantly linked with the risk of cancer development. This meta-analysis was registered at INPLASY (registration number: INPLASY202270073).

Impact of high-dose vitamin C on the mortality, severity, and duration of hospital stay in COVID-19 patients: A meta-analysis.

Background and Aims: Vitamin C has been predicted to be effective as an antioxidant in treating various ailments, including viral infections such as pervasive coronavirus disease (COVID-19). With this meta-analysis, we looked to ascertain the relationship between high-dose vitamin C administration and mortality, severity, and length of hospitalization of COVID-19 patients. Methods: We collected articles from PubMed, Google Scholar, ScienceDirect, SAGE, and Cochrane databases between January 1, 2020, and May 30, 2022. Odds ratio (ORs) with corresponding 95% confidence interval (CI) and p value were calculated to assess the connection of high-dose vitamin C in COVID-19 patients' mortality and severity. The length of hospitalization was calculated and pooled with the mean difference (MD), 95% CI, and p value. Review manager 5.3 was used to carry out this meta-analysis. Results: This meta-analysis included 15 complete studies involving 2125 COVID-19 patients. Our study demonstrated a significant correlation between vitamin C consumption and death. Vitamin C consumption significantly reduces mortality risk with COVID-19 patients (OR = 0.54, 95% CI = 0.42-0.69, p < 0.00001). Furthermore, there was a link between the severity of COVID-19 and the intake of vitamin C. Patients who consumed vitamin C showed 0.63 times less severity than those who did not take vitamin C (OR = 0.63, 95% CI = 0.43-0.94, p = 0.02). Patients taking vitamin C spent slightly more time in hospital than those who did not take vitamin C (MD = 0.19, 95% CI = -1.57 to 1.96, p = 0.83). Conclusions: During COVID-19, there was a substantial advantage in taking supplementary vitamin C, at least in terms of severity and mortality.

A systematic review and meta-analysis of abnormalities in hematological and biochemical markers among Bangladeshi COVID-19 cases.

Background and Aims: Abnormalities in hematological and biochemical markers are assumed to be associated with the progression of COVID-19 disease. This meta-analysis was performed to assess the consequences of abnormalities of biomarkers (D-dimers, C-reactive protein [CRP], serum ferritin, lactate dehydrogenase [LDH], random blood sugar [RBS], absolute neutrophil count [ANC], neutrophil to lymphocyte ratio (NLR), serum creatinine, and hemoglobin) in the Bangladeshi COVID-19 patients. Methods: The data of biomarker levels in Bangladeshi COVID-19 patients were gathered from five databases: PubMed, ScienceDirect, Web of Science, Google Scholar and Bangladesh Journals Online between January 2020 to March 2022. Review Manager 5.4 was used for the meta-analysis, and Egger's test and Begg-Mazumdar's rank correlation were used to investigate publication bias. Results: This study included 1542 patients with 567 severe and 975 nonsevere statuses. Based on the accumulated data synthesis, there is a strong correlation between disease severity and different biomarkers, including D-dimer, CRP, ferritin, LDH, RBS, NLR, and serum creatinine (MD = 1.16, p = 0.0004; MD = 22.97, p = 0.003; MD = 419.26, p < 0.00001; MD = 118.37, p = 0.004; MD = 1.96, p = 0.02; MD = 1.26, p = 0.02; and MD = 0.31, p = 0.008, respectively). A significantly decreased correlation was observed for hemoglobin levels in severe COVID-19 patients (MD = -0.73, p = 0.10). Conclusion: The elevated biomarkers level was noticed in severe cases compared to nonsevere patients, revealing that D-dimer, CRP, ferritin, LDH, RBS, NLR, and serum creatinine are significantly correlated to COVID-19 severity. Only lower hemoglobin level was found to be associated with COVID-19 severity.

Catalase C262T genetic variation and cancer susceptibility: A comprehensive meta-analysis with meta-regression and trial sequential analysis.

Several genetic association studies have analyzed the link between the catalase (CAT) C262T variant and different cancers, but the findings remain controversial. Our research centered on establishing a comprehensive correlation between the C262T variant and different cancers. This study was conducted using RevMan 5.4 software following the PRISMA 2020 guidelines. For this meta-analysis, 53 case-control studies (18,258 cases and 47,476 controls) were chosen. The analysis revealed that three genetic models were statistically linked (P < 0.05) to overall cancer susceptibility in codominant model 2 (COD2): odds ratio (OR) = 1.16, COD3: OR = 1.21, recessive model (RM): OR = 1.20). After stratification by ethnicity, a significant link (P < 0.05) was found in Caucasians (COD2: OR = 1.18, COD3: OR = 1.17, over-dominant model (ODM): OR = 1.19) and Asians (COD3: OR = 1.49). Subgroup analyses revealed a significant correlation (P < 0.05) with blood-and-bone-marrow-related cancer, skin cancer, gastrointestinal-tract-related cancer, prostate cancer, and gynecologic cancer. Three genetic models in population-based controls (COD2: OR = 1.19, COD3: OR = 1.17, RM: OR = 1.19) and two genetic models in hospital-based controls (COD3: OR = 1.40, RM: OR = 1.24) were found to be significantly correlated (P < 0.05) with cancer. Also, three genetic models for polymerase chain reaction-restriction fragment length polymorphism (COD3: OR = 1.46; RM: OR = 1.34, ODM: OR = 0.80) and three models for MALDI-TOF + MassARRAY (COD2: OR = 1.32, RM: OR = 1.26, allele model: OR = 1.14) genotyping methods showed significant association (P < 0.05) with cancer. The meta-regression showed that the quality scores might be a source of significant heterogeneity under the COD2 model (coefficient = 0.176, P = 0.029). Trial sequential analysis also validated the adequacy of the sample size on overall findings. Our results indicate that CAT C262T variant is associated with overall cancer susceptibility, especially in Caucasians and Asians. This variant may also be associated with blood-and-bone-marrow-related, GIT-related, prostate, skin, and gynecological cancers.

Pharmacological investigation of analgesic and antipyretic activities of methanol extract of the whole part of Aeginetia indica.

ETHNOPHARMACOLOGICAL RELEVANCE: Aeginetia indica (Linn.), commonly known as aankuri bankuri, guan-jen-huang, forest ghost flower, dok din daeng, dapong tubo; is a root parasitic plant of the Orobanchaceae family native to South and South-East Asian region. Different parts of the plant are traditionally used to treat fever, pain, inflammation, arthritis, cough, diabetes, and chronic liver disease. Local practitioners often recommend this plant as a folk remedy for dermal swelling, painful menstrual periods, wounds, and knee pain. However, the antipyretic and analgesic activity of A. indica have never been investigated. AIM OF THE STUDY: The present study was aimed to evaluate the analgesic and antipyretic potential of Aeginetia indica plant extract to verify its effectiveness as reported in traditional uses. MATERIALS AND METHODS: Preliminary phytochemical analysis of Aeginetia indica crude extract was performed using previously established methods and antioxidant capacity was determined by phosphomolybdenum assay. In vivo analgesic activity of Aeginetia indica methanol extract (AiME) was evaluated by acetic acid-induced writhing test, formalin-induced paw licking test, and hot plate test model. The antipyretic activity was studied in Baker's yeast induced pyrexia model. RESULTS: Phytochemicals screening revealed cardiac glycosides, saponins, phenols, tannins, and flavonoids in the crude extract of Aeginetia indica. Total phenolic and flavonoid content were recorded as 101 ± 1.1 mg GAE/g of the extract and 35 ± 0.8 mg QE/g of the extract, respectively. The total antioxidant capacity observed in phosphomolybdenum assay was 68.3 ± 1.3 mg ascorbic acid equivalent per gram of the extract. AiME showed significant dose-dependent analgesic activity against acetic acid-induced writhing, formalin-induced paw licking, and hot plate pain model. A higher dose of A. indica (200 mg/kg) produced significant (P < 0.001) inhibition of writhing by 69% whereas, standard aspirin showed maximum 85.6% inhibition. AiME at all doses showed a significant (P < 0.001) decrease of paw licking time in both early neurogenic and late inflammatory pain phase of formalin-induced licking test. In the hot plate test, AiME at a 200 mg/kg dose produced antinociceptive activity (55.18%) higher than the standard ketorolac (49.88%) at 1 h. However, after 2 h, ketorolac showed a maximum effect of 62.66% and AiME 200 mg/kg showed a 60.24% effect. A significant (P < 0.001) reduction of rectal temperature (4.54 °F↓) was recorded for AiME 200 mg/kg, which was higher than the standard paracetamol (3.86 F°↓) after 24 h of treatment. CONCLUSION: The in vivo investigational studies' results demonstrated promising analgesic and antipyretic activities of A. indica, which supported the claim of its folk uses.

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.

Impact of age, sex, comorbidities and clinical symptoms on the severity of COVID-19 cases: A meta-analysis with 55 studies and 10014 cases.

PURPOSE: Severe acute respiratory coronavirus 2 (SARS-CoV-2) cases are overgrowing globally and now become a pandemic. A meta-analysis was conducted to evaluate the impact of age, sex, comorbidities, and clinical characteristics on the severity of COVID-19 to help diagnose and evaluate the current outbreak in clinical decision-making. METHODS: PubMed, ScienceDirect, and BMC were searched to collect data about demographic, clinical characteristics, and comorbidities of COVID-19 patients. Meta-analysis was conducted with Review Manager 5.3. Publication bias was assessed using Egger's test and Begg-Mazumdar's rank correlation. RESULTS: Fifty-five studies were included in this meta-analysis, including 10014 patients with SARS-CoV-2 infection. Male cases and cases with an age of ≥50 years (OR = 2.41, p < 0.00001; RR = 3.36, p = 0.0002, respectively) were severely affected by SARS-CoV-2. Patients having age≥65 years are not associated (p = 0.110) with the severity of COVID-19. Presence of at least one comorbidity or hypertension, diabetes, cerebrovascular disease, cardiovascular diseases, respiratory disease, malignancy, chronic kidney disease and chronic liver diseases individually increased the severity of COVID-19 cases significantly (OR = 3.13, p < 0.00001; OR = 2.35, p < 0.00001; OR = 2.42, p < 0.00001; OR = 3.78, p < 0.00001; OR = 3.33, p < 0.00001; OR = 2.58, p < 0.00001; OR = 2.32, p < 0.00001; OR = 2.27, p = 0.0007; OR = 1.70, p = 0.003, respectively). Clinical manifestation such as fever, cough, fatigue, anorexia, dyspnea, chest tightness, hemoptysis, diarrhea and abdominal pain (OR = 1.68, p = 0.0001; OR = 1.41, p = 0.004; OR = 1.26, p = 0.03; OR = 2.38, p < 0.0001; OR = 4.30, p < 0.00001; OR = 2.11, p = 0.002; OR = 4.93, p < 0.0001; OR = 1.35, p = 0.03; OR = 2.38, p = 0.008, respectively) were significantly associated with the severity of cases. No association of severity was found with myalgia, pharyngalgia, nausea, vomiting, headache, dizziness and sore throat (p > 0.05). No publication bias was found in case of age (≥50 years, age≥65 years), comorbidities and clinical manifestations. CONCLUSIONS: Males patients and elderly or older patients (age ≥50 years) are at higher risk of developing severity, whereas comorbidities and clinical manifestations could significantly affect the prognosis and severity of COVID-19.

A Review on Current Repurposing Drugs for the Treatment of COVID-19: Reality and Challenges.

The coronavirus disease 2019 (COVID-19) caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a global pandemic with a high growth rate of confirmed cases. Therefore, therapeutic options are desperately urgent to fight with this damning virus. As it may take years to develop a specific therapy of COVID-19, it is urgent to emphasize the repurposing of drugs used for other conditions. This study reviewed the most common drugs for COVID-19 based on available online literature representing the latest in vitro clinical trial database, rational of use, adverse effects, potential toxicities, and US National Institute of Health (NIH) recommendation to use for COVID-19. Based on the preliminary data from clinical trials and considering the NIH and FDA recommendation, remdesivir and convalescent blood products are the most promising potential for COVID-19 treatment. The use of chloroquine, hydroxychloroquine, favipiravir, ivermectin, and colchicine might also be effective. However, furthermore, in vivo investigations are needed in detail individually and in combination for possible benefits in humans. Besides, tocilizumab might be deemed as adjunctive therapy for patients with cytokine release syndrome. However, lopinavir-ritonavir, anakinra, and sarilumab had not proven their clinical efficacy. Eventually, sarilumab has been withdrawn from sponsored clinical trials based on the preliminary data. Baricitinib and ruxolitinib have the additive immunosuppressive effect. Consequently, all of these drugs are being evaluated with further studies. In addition, drug-drug interaction and safety concerns must be taken into account before the administration of the recommended drugs.

Antipyretic and anti-nociceptive effects of methanol extract of leaves of Fimbristylis miliacea in mice model.

ETHNOPHARMACOLOGICAL RELEVANCE: Fimbristylis miliacea (L.) Vahl (Cyperaceae) is a grass like herb usually grows as a weed in rice fields and is mainly distributed in tropical or sub-tropical countries of south and south-east Asia, central America, northern Australia and west Africa. The plant has been traditionally used to treat fever as a form of poultice. AIM OF THE STUDY: The present study aimed to investigate antipyretic and anti-nociceptive effects of methanol extract of leaves of Fimbristylis miliacea in mice model. MATERIALS AND METHODS: Antipyretic effect of Fimbristylis miliacea was examined using Baker's yeast induced hyperthermia test. Anti-nociceptive effect was investigated using acetic acid induced writhing test, formalin induced hind paw licking test and hot plate test. RESULTS: The extract at concentration of 400 mg/kg produced significant reduction in body temperature after 0.5 h of administration (4.12 °F, p ≤ 0.001) and continued to decrease (after 4 h, 5.92 °F, p ≤ 0.001). Extracts at 100 mg/kg and 200 mg/kg decreased the temperature by about 2.77 °F (from 99.47 °F to 96.7 °F) and 5.58 °F (98.2 °F-92.62 °F) respectively after 4 h whereas paracetamol dropped by about 7.2 °F (p ≤ 0.001). The extract showed significant decrease in number of writhes at all concentrations. Highest effect was found at 200 mg/kg having 35.7 writhes (p ≤ 0.001), much lower than control (89.2); standard drug diclofenac showed 23.2 writhes. Percent inhibition of writhing were 54.26 and 73.99 for 200 mg/kg and diclofenac respectively. The result of hind paw licking test also corroborated writhing test. Significant reduction in percent inhibition of licking was observed mainly in late phase. Percent inhibition of licking were 93.77 and 51.55 for 400 mg/kg extract and diclofenac respectively. In hot plate test, extract at 400 mg/kg showed significant increase in latency from 10.77 s to 13.59 s (p ≤ 0.05). Extract at this dose after 2 h demonstrated greater percent maximal effect (43.26%) compared to ketorolac (40.19%). CONCLUSION: The experiment confirmed the traditional use of F. miliacea in the treatment of fever with possible anti-nociceptive effects.