Tusha Sharma

Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer and poses significant treatment challenges due to fewer available options. Creating highly specific and precise anticancer therapies continues to be a significant challenge for TNBC. Previous studies showed that combining drugs or adding chemotherapy to other therapies has significantly improved patient prognosis and proved to be an effective strategy for treating TNBC compared to using chemotherapeutic drugs alone targeting TNBC pathways. One such combination is a PARP inhibitor (PARPi) with an immune checkpoint inhibitor (ICI). In this study, we explored the transcriptomic profiles of the combination of Olaparib (a PARP inhibitor) and atezolizumab (a monoclonal antibody targeting PD-L1) in cells derived from African American (AA) and White populations. Cell viability analyses showed that treatment with olaparib, atezolizumab, and their combination reduced cell viability compared with the control condition, with the combination treatment showing a significant effect. Our transcriptional profiling revealed that both up- and down-regulated genes exhibited widespread suppression of proliferation and biosynthesis pathways, along with selective activation of immune and stress-related pathways. Our functional enrichment analysis revealed significant changes in DNA damage response, chromatin organization, RNA regulatory processes, immune signaling, and inflammatory responses. In conclusion, our study’s results provide valuable insights into key features of combination therapy, which may help guide the more targeted development of these regimens.

Triple-negative breast cancer (TNBC) is the most aggressive form of breast cancer and poses significant treatment challenges due to fewer available options. Creating highly specific and precise anticancer therapies continues to be a significant challenge for TNBC. Previous studies showed that combining drugs or adding chemotherapy to other therapies has significantly improved patient prognosis and proved to be an effective strategy for treating TNBC compared to using chemotherapeutic drugs alone targeting TNBC pathways. One such combination is a PARP inhibitor (PARPi) with an immune checkpoint inhibitor (ICI). In this study, we explored the transcriptomic profiles of the combination of Olaparib (a PARP inhibitor) and atezolizumab (a monoclonal antibody targeting PD-L1) in cells derived from African American (AA) and White populations. Our results demonstrated that combining Olaparib (Ola) and Atezolizumab (Atz) significantly reduced cell viability in both AA and White cell lines, compared to either agent alone. Our transcriptional profiling results showed that in both up- and down-regulated genes, there was widespread suppression of proliferation and biosynthetic gene networks, and selective activation of immune and stress-related pathways. Our transcriptional profiling revealed that both up- and down-regulated genes exhibited widespread suppression of proliferation and biosynthesis pathways, along with selective activation of immune and stress-related pathways. Our functional enrichment analysis revealed significant changes in DNA damage response, chromatin organization, RNA regulatory processes, immune signaling, and inflammatory responses. In conclusion, our study’s results provide valuable insights into key features of combination therapy, which may help guide the more targeted development of these regimens.

Aim: Diabetic peripheral neuropathy (DPN) induces chronic neuropathic pain in diabetic patients. Current treatments like pregabalin and duloxetine offer limited efficacy. This study evaluates combining pregabalin and duloxetine versus pregabalin alone for DPN pain relief, and explores gene modulation (PPARγ and Akt) to understand neuropathic pain's molecular basis.Materials & methods: Diabetic patients with DPN were randomized into groups receiving combination therapy or pregabalin alone for 4 weeks. Pain intensity, gene expression and quality of life were assessed.Results: Combination therapy significantly reduced pain, improved quality of life and upregulated PPARγ and Akt genes compared with monotherapy.Conclusion: Pregabalin and duloxetine combination therapy in DPN led to PPARγ mRNA upregulation and negative correlation of Akt gene expression with pain scores. This combination therapy effectively reduced pain and improved quality of life.Clinical Trial Registration: CTRI/2021/02/031068.

The human gut microbiota can be potentially disrupted due to exposure of various environmental contaminants, including pesticides. These contaminants enter into non-target species in multiple ways and cause potential health risks. The gut microbiota-derived metabolites have a significant role in maintaining the host’s health by regulating metabolic homeostasis. An imbalance in this homeostasis can result in the development of various diseases and their pathogenesis. Pesticides have hazardous effects on the host’s gut microbiota, which is evident in a few recent studies. Therefore, there is an urgent need to explore the effect of pesticide on gut microbiota-mediated metabolic changes in the host, which may provide a better understanding of pesticide-induced toxicity. The present review summarizes the pesticide-induced effects on gut microbiota, which in turn, induces changes in the release of their secondary metabolites that could lead to various host health effects.

Introduction: Nephrolithiasis is pathological calcification in the excretory passages of the body and is prevalent among 7.6% of Indians. We aimed to study the various risk factors associated with renal stones from India. Method: It was a hospital-based case-control study conducted over 18 months in a tertiary hospital in Delhi. Cases were defined as patients with renal stones diagnosed on the basis of history and radiological examination. Controls were similar to cases in all respects except for the diagnosis and selected from the hospital. A total of 18 risk factors, including age, gender, heavy metals, stress, metabolic factors, alcohol intake, dietary habits, co-morbidities, etc. were assessed. Logistic regression analysis was performed to calculate the strength of the risk associations. Results: In the analysis of 60 cases and controls, we found 6 times, 5.5 times, and 2.4 times increased odds of renal stones in patients with increased arsenic, cadmium, and lead concentrations in blood, respectively. Similarly, there are 3 times increased odds of renal stones in patients suffering from stress. Conclusions: Exposure to smoke, occupation dust, and contaminated water may lead to an increased ingestion/inhalation of heavy metals like cadmium, arsenic, and predisposing people to an increased risk of renal stones.

The transformation of ovarian surface epithelial cells, stromal cells, sex cord, or germ cells initiates ovarian malignancy. Epithelial ovarian cancer (EOC) is clinically silent with vague, non-specific symptomatology and is generally diagnosed at an advanced stage, resulting in a high mortality rate. The known main etiological factors are: age at menarche and menopause (early menarche or late menopause), use of oral contraception (estrogen and/or progesterone), family history, genetic factors, inflammation, occupational and environmental exposure. The study is intended to assess the association between blood organochlorine pesticide (OCP) levels and polymorphic status of phase I and phase II metabolizing enzymes (CYP1A1, GSTM1, and GSTT1) in the pathogenesis of epithelial ovarian cancer. The study included 200 subjects in total, of which 100 were epithelial ovarian cancer cases and 100 were controls. Estimation of blood organochlorine pesticide levels was carried out using gas chromatography and significantly high levels of beta-hexachlorocyclohexane (β-HCH), endosulfan-I, endosulfan-II, dichlorodiphenyltrichloroethane (pʹpʹ-DDT), dichlorodiphenyldichloroethylene (pʹpʹ-DDE) were observed in cases as compared to controls ( P-value = 0.029, 0.042, 0.044, 0.039 and 0.037 respectively). For studying the polymorphism of CYP1A1, GSTM1/T1, PCR-RFLP, AS-PCR and multiplexing were performed and the frequency of null deletion of GSTM1/T1 was significantly higher in epithelial ovarian cancer cases. Regression model testing was also performed to check the interactive effect of organochlorine pesticide levels and polymorphic variant of genes keeping CA-125 as the dependent variable and observed a statistically significant role of genotypic/environmental interaction in epithelial ovarian cancer cases in the North Indian population. Impact statement: Among pervasive environmental toxins, OCPs are one of the largest and most hazardous classes of contaminants in use around the world. Because these compounds possess the estrogen mimicking properties, the accumulation of these compounds in the human body may be a risk for several hormone-dependent diseases. EOC is hormonally dependent cancer and the mortality rate due to this disease is increasingly prevalent, and it has become imperative to explore the role of OCPs in the disease pathogenesis. The present study highlights the significant association of high OCPs level in the disease pathogenesis. It is also observed that the polymorphism in xenobiotic metabolism enzymes alters the predisposition of OCPs. The synergistic effect of gene polymorphism (CYP1A1, GSTM1, and GSTT1) and non-occupational exposure to OCPs was also assessed considering CA125 level as dependent variable with the risk of EOC and concluded that there exist a potential role of genotypic/environmental interaction in the etiology of EOC.