Effects of Low and High Doses of Aspirin on Inflammatory Markers in Diabesity Patients: A Quasi-Experimental Study.

Introduction The intertwined nature of obesity and diabetes, termed diabesity, is a significant health concern. Aspirin has been recognized for its potential in mitigating inflammation-related health issues, a key concern in managing diabesity. However, the optimal aspirin dosage and its impact on specific inflammatory markers, viz. high-sensitivity C-reactive protein (hs-CRP) and interleukin (IL)-6, over time remain a subject of ongoing research. Objective This study investigated the effects of different doses of aspirin (150mg and 300mg) on the levels of hs-CRP and IL-6 over a period of 6 months. Methods This cross-sectional observational quasi-experiment study involved 125 confirmed type-2 diabetes mellitus (T2DM) patients with obesity aged ≥40 years. Blood samples were collected for analyzing hs-CRP and IL-6 levels. Demographics and clinical characteristics, such as BMI, waist-hip ratio, blood parameters, fasting blood sugar (FBS), and hs-CRP, were analyzed. Results At baseline, both the 150 mg and 300 mg aspirin dose groups had similar median levels of hs-CRP. After two months, there was no significant difference (p=0.150). However, by six months, the 150mg dose group had a significantly higher median hs-CRP than the 300 mg dose group (p=0.003). The 150 mg dose group had a significantly higher median level of IL-6 levels at baseline (median; 40.0) compared to the 300 mg dose group (median; 2.27, p<0.0001). After two months, the levels of IL-6 in both groups were similar (median; 2.27 and 2.23 respectively, p<0.0001). By the end of six months, the groups had no significant difference (median; 0.53 and 2.22 respectively, p=0.128). Conclusion The dose of aspirin may significantly impact the levels of hs-CRP and IL-6 over time, with the effects being more pronounced after six months of treatment. These findings suggest that aspirin, a commonly used and cost-effective medication, could potentially be leveraged in a more targeted manner to manage inflammation (CRP and IL-6 levels) in individuals with diabesity.

Transfluthrin is Associated with High Susceptibility to Asthma in Children with Promoter Variants of Beta Chain of High-Affinity Receptor IgE and Tumour Necrosis Factors-α Genes.

This study investigates the genetic variations in FcεR1ß-109 C/T (rs512555) and TNF-α-308 G/A (rs1800629) genes and examines whether the mosquito repellent transfluthrin (TFT) modifies the risk for asthmatic children. A case-control study was conducted involving 130 asthmatic children and 123 age-sex matched controls. Differential leukocyte counts, IgE, and hs-CRP levels were estimated using a five-part haematology analyzer and Beckman Coulter (AU480), respectively. Genetic variations in FcεR1ß-109 and TNF-α-308 were analysed using restriction fragment length polymorphism. Serum TFT levels were measured using gas chromatography-tandem mass spectrometry. Asthmatic children had significantly increased total leukocyte, neutrophil, lymphocyte, eosinophil, and basophil counts (p < 0.0001), while their monocyte counts were lower compared to controls (p < 0.0001). TFT levels were higher in asthmatic children (1.38 ± 0.91 vs. control 0.69 ± 0.41µg/L, p < 0.0001), which predominantly induced wheezing. Elevated TFT levels were associated with an increased risk of childhood asthma (OR: 3.08, p < 0.0001). Children with the FcεRIß TT (OR: 2.39, p < 0.017) and TNF-α GG genotypes (OR: 7.17, p < 0.0001) were more susceptible to asthma. TFT synergistically enhanced the risk of asthma in both FcεRIß-109 TT (OR: 5.3, p = 0.001) and TNF-α-308 GG (OR: 17.18, p < 0.0001) genotypes. TFT levels were correlated with IgE (r = 0.363; p = 0.006), hs-CRP (r = 0.324; p = 0.049) and eosinophil (r = 0.300; p = 0.038), respectively. IgE and eosinophils were correlated (r = 0.599, p = 0.001) in the FcεRIß TT genotype-carrying asthmatic children. Similarly, neutrophils and hs-CRP were correlated (r = 0.768, p < 0.0001) in asthmatic children with TNF-α GG genotype. The risk of asthma is inherently higher in children with FcεRIß TT and TNF-α GG variants. TFT exposure amplifies the risk of asthma in children among all the subgenotypes of both genes. TFT influences IgE and eosinophil in FcεRIß TT genotype while it influences neutrophils and hs-CRP in TNF-α GG genotypes.

Impact of essential metals on insulin sensitivity and fetuin in obesity-related type 2 diabetes pathogenesis.

Purpose: Essential metals may be crucial in obesity and type 2 diabetes (T2DM); diabesity pathogenesis and consequences. This study aimed to determine the metal levels in obese and non-obese patients with and without T2DM and their relationships with fetuin-A(Fet-A) levels, insulin sensitivity, and insulin resistance. Methods: A total of 314 participants were enrolled, with 160 newly diagnosed T2DM patients and 154 non-T2DM subjects categorized into diabetic obese (n = 57), diabetic non-obese (n = 103), non-diabetic obese (n = 48), and non-diabetic non-obese (n = 106) subgroups. Fet-A, insulin sensitivity (QUCKI)/resistance (HOMA-IR), fasting glucose, and body mass index (BMI) were assessed. The essential metals were measured using inductively coupled plasma mass spectroscopy (ICP-MS). Results: Fet-A levels were 3-fold higher (1391.4 ± 839.8 ng/ml) in T2DM patients than in non-T2DM (2165.6 ± 651.9 vs. 424.3 ± 219.1 ng/ml, p < 0.0001). Fet-A levels were 2.3-fold higher in the diabetic obese group than in the diabetic non-obese group (p < 0.0001). Fet-A levels were 2.0-fold higher in the diabetic non-obese group than in the non-diabetic obese group (p < 0.0001). Fet-A levels were positively correlated with insulin resistance (HOMA-IR) (r = 0.34, p < 0.0001) and negatively correlated with insulin sensitivity (QUIKI) (r = -0.41, p < 0.0001).Cu, Se, Zn, and Fe levels were significantly lower in diabetic patients than in non-diabetic patients (p < 0.05). Se and Zn were significantly correlated with Fet-A (r = -0.41, p = 0.049 and r = -0.42, p = 0.001, respectively). Se and Zn were also correlated with insulin resistance (HOMA-IR) (r = -0.45, p = 0.049 and r = -0.36, p = 0.012, respectively) and insulin sensitivity (QUIKI) (r = 0.49, p = 0.042 and r = 0.30, p = 0.003, respectively). Similarly, Fe was negatively correlated with insulin levels (r = -0.33, p = 0.04) and insulin sensitivity (r = -0.34, p = 0.30). However, Mn was significantly correlated with Fet-A (r = 0.37, p = 0.001) and insulin resistance/sensitivity (r = 0.24, p = 0.026 and r = -0.24, p = 0.041) respectively in the diabetic obese group. Mg was an independent predictor of diabesity. Conclusions: Mg play a significant role in obesity-related T2DM pathogenesis and complications via Fet-A, insulin sensitivity, and resistance modifications.

Impact of glutathione S transferases P1 (Ile105Val) variants on the risk of GSTp, phosphorylated c-Jun kinase, and P53 phenotypic expression and their implications on overall survival outcomes in non-small cell lung cancer patients treated with chemotherapy.

AIM: This study focused on GST-M1, T1 null, and P1 Ile105Val variant genotypes associated with the risk of altered expression of GSTp, pJNK, and P53 in NSCLC patients. These markers and overall survival (OS) were correlated with a key set of clinicopathological characteristics. METHODS: Genotyping of GST- M1, T1 (+/-), and P1 (Ile105Val) was performed using PCR-RFLP.The expression of GSTp, pJNK, and P53 phenotypes was assessed by immunohistochemistry. The Spearman test was used to examine the correlation between GSTp, pJNK, and P53. Kaplan-Meier test was used for OS analysis. RESULTS: GSTP1 Val/Val and Ile/Val genotypes notably increased GSTp expression by 1.8 and 1.7 fold, respectively (p = 0.04,p = 0.06). GSTP1 Val/Val and Ile/Val genotypes considerably reduced P53 expression by 0.61 and 0.57 fold, respectively (p = 0.03& p = 0.05), respectively. GSTp, pJNK, and P53 were significantly co-expressed (p < 0.001). GSTp and pJNK expression showed a moderate negative correlation (ρ = -0.32, p = 0.046). In contrast, GSTp and P53 expression exhibited a strong negative correlation (ρ = -0.53, p < 0.0001). There was no correlation between P53 and pJNK expression(ρ = 0.07, p = 0.54). The patient's median OS was 8.9 months, and it was significantly related to pack-years, stage, metastasis, and GSTM1(-/-) genotypes (p > 0.05). SQCLC showed poor OS than ADC (5.7 months vs.9.1 months, p = 0.2). Stage IV and metastasis significantly reduced the OS (p = 0.001). The tumour size and lymph nodes reflected poor OS (p = 0.07&p = 0.06). Gemcitabine+Cisplatin and Gefitinib showed a slightly higher rate of survival (9.3 months and 8.1 months) than Pemtrexe+Cisplatin treatment (7.0 months,p = 0.8). Multivariate analysis revealed that pack-years and GSTp were independent predictors for OS (p = 0.03). CONCLUSION: GSTp, pJNK, and P53 showed interconnected cascading. Age, pack-year, stage, and GSTp were found to be significant predictive factors for OS.Pack-years, GSTp independent OS predictor.

Independent and Interactive Effect of CYPs and GSTs Genetic Variants and Tobacco Smoking on the Risk of Non-Small Cell Lung Carcinoma.

BACKGROUND: CYP and GST gene families detoxify tobacco carcinogens and have been linked to the risk of non-small cell lung carcinoma (NSCLC). AIM: Independent and combined effects of CYP and GST genetic variations and smoking on the risk of non-small cell lung carcinoma (NSCLC) and its sub-histological types. METHODS: We modelled an epistatic interaction via the effects of particular genotypes in two genes as OR (odds ratio), OR1, and OR2, a combination of both genotypes were characterized as ORcombine. In contrast, the two ORs' epistatic interaction for the individual genotypes has been represented as ORinteraction = ORcombine/(OR1 × OR2). RESULTS: The variant genotypes of CYP2A6 (OR:4.2, p <0.001), GSTT1 (OR:3.9, p <0.001), and GSTM1 (OR: 4.5, p <0.001) were showed a significant risk with NSCLC. GSTM1 (del.)/CYP2A6 (variant) genotype was associated with a higher risk of NSCLC (OR:12.5, p <0.001). GSTM1 (del.)/CYP2A6 (Ser/Pro+Pro/Pro) and GSTM1 (del.)/CYP2A13 (CT+TT) interacted redundantly (ORintraction = 0.66 and 0.64). A co-suppressive interaction was observed between GSTT1 (del.)/CYP2A6 (Ser/Pro+Pro/Pro) (ORintraction = 0.41). Simultaneously, both GSTT1/GSTM1 del. genotype was associated with a significantly higher risk to NSCLC. In contrast, GSTT1 del./GSTM1 del. genotype interaction displayed a co-suppressive effect (ORintraction = 0.15). CYP1A1(TC+CC)/CYP2A13(CT+TT)mutually interacted synergistically (ORintraction = 1.27).CYP1A1 (TC+CC)/GSTP1 (Val/Val+Ile/Val) genotype demonstrated an additive (ORintraction = 1) effect. GSTP1(Val/Val+Ile/Val) interacts with GSTT1 (del.) genotype exerted a suppressive effect (ORintraction = 0.69). CYP2A6 in smokers increased risk by 4.2 (p = 0.001) to 5.6 fold (p <0.001), while GSTM1 and GSTT1 were independent of smoking. CONCLUSION: Epistatic interactions revealed that CYPs/GSTs might follow a web of the interactions to modify the risk of NSCLC.