Revitalizing Cancer Treatment: Exploring the Role of Drug Repurposing.

Cancer persists as a global challenge necessitating continual innovation in treatment strategies. Despite significant advancements in comprehending the disease, cancer remains a leading cause of mortality worldwide, exerting substantial economic burdens on healthcare systems and societies. The emergence of drug resistance further complicates therapeutic efficacy, underscoring the urgent need for alternative approaches. Drug repurposing, characterized by the utilization of existing drugs for novel clinical applications, emerges as a promising avenue for addressing these challenges. Repurposed drugs, comprising FDA-approved (in other disease indications), generic, off-patent, and failed medications, offer distinct advantages including established safety profiles, cost-effectiveness, and expedited development timelines compared to novel drug discovery processes. Various methodologies, such as knowledge-based analyses, drug-centric strategies, and computational approaches, play pivotal roles in identifying potential candidates for repurposing. However, despite the promise of repurposed drugs, drug repositioning confronts formidable obstacles. Patenting issues, financial constraints associated with conducting extensive clinical trials, and the necessity for combination therapies to overcome the limitations of monotherapy pose significant challenges. This review provides an in-depth exploration of drug repurposing, covering a diverse array of approaches including experimental, re-engineering protein, nanotechnology, and computational methods. Each of these avenues presents distinct opportunities and obstacles in the pursuit of identifying novel clinical uses for established drugs. By examining the multifaceted landscape of drug repurposing, this review aims to offer comprehensive insights into its potential to transform cancer therapeutics.

Association of salivary levels of DNA sensing inflammasomes AIM2, IFI16, and cytokine IL18 with periodontitis and diabetes.

BACKGROUND: Aberrant deoxyribonucleic acid (DNA) contributes to inflammasome orchestrated progression of chronic inflammatory diseases like diabetes and periodontitis. The purpose of the present study was to estimate salivary levels of DNA sensing inflammasomes, absent in melanoma 2 (AIM2), interferon γ inducible protein (IFI16), and cytokine interleukin 18 (IL18) in individuals with periodontitis, diabetes, and healthy controls and interpret its association with periodontal and diabetic parameters. METHODS: Salivary levels of AIM2, IFI16, and IL18 were estimated by enzyme linked immunosorbent assay (ELISA) in a total of 120 individuals (n = 30 in each group), namely, healthy (Group 1), periodontitis (Group 2), diabetes (Group 3), and diabetes with periodontitis (Group 4). Correlations of inflammasome levels and periodontal clinical parameters-plaque index (PI), gingival index (GI), bleeding on probing (BOP), probing pocket depth (PPD), clinical attachment level (CAL), and periodontal inflamed surface area (PISA) were performed. Multiple regression was carried out to predict AIM2 and IFI16 with various independent variables. RESULTS: The mean salivary levels of AIM2, IFI16, and IL18 were highest in diabetes with periodontitis (Group 4) and least in healthy (Group 1) and statistically significant between the groups (p = 0.000). Significant positive correlation between clinical periodontal parameters and AIM2, IFI16, and IL18 was present (p ≤ 0.05). Multiple regression showed glycated hemoglobin (HbA1C) (p = 0.002), GI (p = 0.016), PISA (p = 0.002), and CAL (p = 0.004) were significant predictors of AIM2, while HbA1C (p = 0.012), PISA (p = 0.003), and CAL (p = 0.007) predicted IFI16. CONCLUSION: The results of the present study showed higher levels of AIM2, IFI16, and IL18 in saliva of individuals with diabetes and periodontitis. HbA1C, PISA, and CAL were significant independent predictors of salivary AIM2 and IFI16 levels.

Role of Gut Microbiota in Breast Cancer and Drug Resistance.

Breast cancer is the most common malignancy in women worldwide. The cause of cancer is multifactorial. An early diagnosis and the appropriate treatment of cancer can improve the chances of survival. Recent studies have shown that breast cancer is influenced by the microbiota. Different microbial signatures have been identified in the breast microbiota, which have different patterns depending on the stage and biological subgroups. The human digestive system contains approximately 100 trillion bacteria. The gut microbiota is an emerging field of research that is associated with specific biological processes in many diseases, including cardiovascular disease, obesity, diabetes, brain disease, rheumatoid arthritis, and cancer. In this review article, we discuss the impact of the microbiota on breast cancer, with a primary focus on the gut microbiota's regulation of the breast cancer microenvironment. Ultimately, updates on how immunotherapy can affect the breast cancer-based microbiome and further clinical trials on the breast and microbiome axis may be an important piece of the puzzle in better predicting breast cancer risk and prognosis.

Possible modulation of glycated protein levels in prehypertension by lipid peroxides.

Glycation and lipid peroxidation are two important processes known to play a key role in complications of many pathophysiological processes. Malondialdehyde (MDA) has been reported to play a possible role in the genesis of glycated proteins. This study was undertaken to unravel the possible association of MDA with glycated hemoglobin and fructosamine in prehypertensive patients. A case-control study was performed on 42 prehypertensive and 30 control subjects. Plasma glucose, MDA, fructosamine, and glycated hemoglobin were analyzed in both the groups. Partial correlation analysis was performed to predict the independent association of MDA and fasting glucose on fructosamine and glycated hemoglobin. Plasma of prehypertensive subjects revealed significantly higher concentrations of lipid peroxides and fructosamine than in controls. Glycated hemoglobin concentrations were also found to be significantly increased in test group when compared with healthy controls. When the effects of fasting glucose on the concentrations of glycated hemoglobin and fructosamine were refuted by partial correlation analysis, MDA was found to be a significant determinant of glycated hemoglobin and fructosamine in subjects with prehypertension. These data also support the premise that lipid peroxides per se could play a role in the glycation of hemoglobin and plasma proteins in prehypertension.

Oxidative stress in prehypertension: rationale for antioxidant clinical trials.

Prehypertension has been recently described as an independent category of blood pressure. Mounting evidence suggests that blood pressure in the prehypertensive range is associated with an increased risk of developing hypertension and cardiovascular disease. Several reports have assigned a critical role for oxidative stress in these disease processes. This review focuses on the clinical and experimental studies done in prehypertension and hypertension within the context of oxidative stress. This article also provides insights into why diverse therapeutic interventions, which have in common the ability to reduce oxidative stress, can impede or delay the onset of hypertension in prehypertension subjects.