Khokon Kanti Bhowmik

Background: Relapse-like ethanol drinking behavior depends on changes in glutamate homeostasis in the mesocorticolimbic circuit. Extracellular glutamate regulation involves multiple transporters, mainly glutamate transporter 1 (GLT-1), which primarily removes the majority of extracellular glutamate; and cystine/glutamate antiporter (xCT) is co-localized with GLT-1 to be involved in this mechanism of maintaining glutamate homeostasis. Aims: Recent studies showed that MC-100093 treatment (i.p.), a β-lactam non-antibiotic known to increase GLT-1 and xCT expression, reduced chronic ethanol consumption in male and female alcohol-preferring (P) rats. This study examined whether MC-100093 may reduce relapse-like ethanol drinking behavior. Methods: P rats (both male and female) had access to 15% and 30% ethanol and water for 5 weeks and were treated with MC-100093 (100 mg/kg, i.p.) during the last 4 days of a 1-week deprivation period (week 6), continuing into 3 days of re-exposure (week 7). Results: MC-100093-treated rats exhibited lower ethanol intake and preference during re-exposure compared to saline-treated groups, across sexes. Additionally, MC-100093 treatment showed a sex difference in ethanol intake and preference after re-exposure. Moreover, MC-100093 attenuated ethanol-induced downregulation of GLT-1 and xCT expression in the medial prefrontal cortex (Prelimbic, PL; and Infralimbic, IL) and nucleus accumbens (core and shell) regions. Importantly, MC-100093 did not affect rat body weights. Conclusions: These results report for the first time the efficacy of GLT-1 modulator, MC-100093, on attenuating relapse-like ethanol drinking behaviors.

Background/Objective: Prolonged ethanol use can induce behavioral and physiological alterations and impair the liver’s capacity to metabolize ethanol, leading to hepatocyte injury. The spectrum of this disease ranges from fat accumulation to severe liver damage, including alcohol-related hepatitis and cirrhosis. MC-100093, a beta-lactam non-antibiotic compound, is known to modulate glutamate transporter-1 (GLT-1) and reduce ethanol drinking. Therefore, this study examined the effects of two optimal doses of MC-100093 on ethanol consumption and, consequently, ethanol-induced hepatic injury in both male and female alcohol-preferring (P) rats. Methods: Animals were divided into four groups and exposed to ethanol for six weeks. In week six, rats received intraperitoneal injections of saline, 100 mg/kg MC-100093, or 150 mg/kg MC-100093 for five consecutive days. Liver tissue samples were analyzed to assess GLT-1 and the cystine/glutamate antiporter (xCT), triglyceride levels, collagen type-1 (COL-1) deposition, and inflammatory cytokines. Results: MC-100093 effectively attenuated ethanol-induced liver damage by decreasing ethanol intake and restoring GLT-1, xCT, and COL-1 levels in the livers of both male and female P rats. Moreover, MC-100093 reversed ethanol-induced inflammation and reduced hepatic triglyceride levels. Conclusions: Our data show that MC-100093 effectively mitigates ethanol-induced liver injury.

Background: Variants of the matrix metalloproteinase (MMP) gene have been associated with multiple malignancies, including stomach, bladder, lung, breast, melanoma, squamous cell skin, and colorectal cancers. Genetic factors often slightly to moderately increase the risk of breast cancer. Objective: This study was conducted to ascertain the correlation between breast cancer patients in Bangladesh and the MMP2 rs243865 and MMP8 rs11225395 polymorphisms. Design: A case-control study Methods: The tetra-primer amplification refractory mutation system polymerase chain reaction (ARMS-PCR) was used for genotyping of 324 healthy individuals and 315 individuals with breast cancer. In addition, we performed in silico expression analysis of MMP2 and MMP8 genes using different databases, such as GEPIA, UALCAN, and GTEx. Results: In the case of MMP2 rs243865 polymorphism, additive model 1 (OR = 1.90, 95% CI = 1.03-3.52), dominant model (OR = 2.07, 95% CI = 1.15-3.72), overdominant model (OR = 1.83, 95% CI = 0.99-3.38), and allelic (OR = 1.93, 95% CI = 1.17-3.17) model were significantly associated with enhanced breast cancer risk. For the MMP8 rs11225395 polymorphism, none of the genetic models showed a significant association with increased breast cancer risk. The logistic regression analyses were adjusted for response status (age, BMI, and marital status). In silico analysis showed that MMP2 was more highly expressed in normal tissues, whereas MMP8 was more highly expressed in breast tissues. Conclusion: Our findings imply that MMP2 (rs243865) polymorphisms correlate with higher breast carcinoma risk but have no relationship with MMP8 (rs11225395) polymorphisms in the Bangladeshi female population.

Background: Ethanol consumption disrupts glutamate homeostasis in several brain regions. The uptake of extracellular glutamate is regulated in the majority by the astrocytic glutamate transporter 1 (GLT-1), and cystine-glutamate exchanger (xCT) contributes to this regulatory effect. Chronic ethanol consumption is well known to downregulate GLT-1 expression in several reward brain regions, including the nucleus accumbens (NAc). Objectives: Recently, we reported that a novel beta-lactam, MC-100093, attenuated ethanol consumption and normalized the expression of GLT-1 in the subregions of the NAc. Based on these findings, we aimed in this study to determine the dose-dependent effect of MC-100093 in attenuating ethanol consumption and whether this attenuating effect is associated with restoration of glutamate uptake. In addition, we focused on whether the effects of MC-100093 on GLT-1 are mediated through the mammalian target of rapamycin (mTOR), protein kinase B (Akt), and nuclear factor-kappa B (NF-κB) signaling pathways. Methods: Male and female alcohol-preferring (P) rats are grouped into 4 groups. Other than control groups all the 3 groups had free access to ethanol (15% and 30% v/v), and water for 5 weeks. On week 6, rats received intraperitoneal injection (i.p.) of MC-100093 at a dosage of 100 or 150 mg/kg, or saline, for 5 days. The Na+ dependent and Na+ independent glutamate uptake is measured by radioactive glutamate uptake assay. The expression of GLT-1, xCT, mTOR, phospho-Akt (p-Akt), kappa light polypeptide gene enhancer in B-cells inhibitor, alpha (IkBa), and NF-κB are determined by Western blot analysis. Results: MC-100093 treatment reduced ethanol drinking in male and female P rats. MC-100093 was associated with an increase in Na+-dependent and Na+-independent glutamate uptake. Furthermore, MC-100093 treatment attenuated ethanol-induced decrease in GLT-1, xCT, NF-κB, and p-Akt expression in the NAc. Conclusions: These findings demonstrate that MC-100093 attenuated ethanol consumption and regulated glutamate uptake through normalizing GLT-1 expression.

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.

Background and Aims: The dengue virus is widespread throughout Bangladesh and significantly contributes to morbidity and mortality. One effective method for preventing further dengue epidemics is to reduce mosquito breeding at the most opportune period each year. This study aims to determine dengue prevalence in 2022 by comparing previous years' data and estimating the period of this disease's most significant incidence.Methods: From the beginning of 2008–December 15, 2022, we looked at the monthly reports of cases made to the Bangladesh Institute of Epidemiology, Disease Control, and Research.Results: According to our findings, there were 61089 confirmed dengue cases in 2022, with 269 fatalities ‐ the highest annual death toll for this disease since 2000. Almost one‐third (32.14%) of all dengue deaths in Bangladesh occurred in 2022 (1 January–15 December), highlighting the severity of the threat posed by this disease in the coming year. Furthermore, we observe that the months in the second half of any year in Bangladesh are the most at risk for dengue transmission. In 2022, Dhaka city and Chittagong are hit the hardest (incidence: 63.07% vs. 14.42%; morality: 63.34% vs. 24.16%), showing the relevance of population density in spreading this fatal disease.Conclusion: Statistics show an increase in dengue cases every day, and the year 2022 will be marked as the peak of the disease's death prevalence. Both the individuals and the government of Bangladesh need to take action to reduce the dissemination of this epidemic. If not, the country will soon be in great peril.

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.

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).

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.

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.