In India, tobacco (nicotine) addiction among youth has increased, leading to substantial socioeconomic burdens, mortality, and morbidity. While minimal short-term nicotine consumption may have antioxidant effects, chronic exposure results in various adverse health outcomes. This study examines the impact of chronic nicotine consumption on cellular oxidative stress and psychological stress, and their correlation with Homocysteine (Hcy) levels in unemployed tobacco consumers. This case-control study included 156 healthy, educated, unemployed male volunteers aged 20–40 years, divided into nicotine-addicted (n = 80) and non-addicted (n = 76) groups. Psychological stress was assessed using perceived stress scales (PSS) and coping self-efficacy (CSE) scales. Oxidative stress markers, including Malondialdehyde (MDA), Superoxide Dismutase (SOD), and Catalase, were measured. Hcy levels were quantified using high-performance liquid chromatography (HPLC). Nicotine-addicted participants exhibited significantly higher perceived stress (p = 0.0001) and lower coping self-efficacy (p = 0.0001) compared to non-addicted individuals. MDA levels in erythrocytes were significantly increased (p = 0.0006), while SOD (p = 0.0001) and Catalase (p = 0.02) activities were significantly decreased in the addicted group. Nicotine intake influenced Hcy concentrations, with 55

Cardiovascular diseases continue to challenge global health, demanding innovative therapeutic solutions. This review delves into the transformative role of mesenchymal stem cells (MSCs) in advancing cardiovascular therapeutics. Beginning with a historical perspective, we trace the development of stem cell research related to cardiovascular diseases, highlighting foundational therapeutic approaches and the evolution of cell-based treatments. Recognizing the inherent challenges of MSC-based cardiovascular therapeutics, which range from understanding the pro-reparative activity of MSCs to tailoring patient-specific treatments, we emphasize the need to refine the pro-regenerative capacity of these cells. Crucially, our focus then shifts to the strategies of the fourth generation of cell-based therapies: leveraging the secretomic prowess of MSCs, particularly the role of extracellular vesicles; integrating biocompatible scaffolds and artificial sheets to amplify MSCs’ potential; adopting three-dimensional ex vivo propagation tailored to specific tissue niches; harnessing the promise of genetic modifications for targeted tissue repair; and institutionalizing good manufacturing practice protocols to ensure therapeutic safety and efficacy. We conclude with reflections on these advancements, envisaging a future landscape redefined by MSCs in cardiovascular regeneration. This review offers both a consolidation of our current understanding and a view toward imminent therapeutic horizons.

Purpose: Majority of the gallbladder cancer (GBC) cases are diagnosed at an advanced stage where chemotherapy alone (or in combination with other treatment methods) is mainly opted as therapeutic approach. However, success or failure of this approach largely depends on the interindividual genetic differences. Careful consideration on the genetic association could assist in the evaluation of patient’s treatment response and survival rate. Hence, the present study aims to investigate the survival of patients with GBC and their treatment response to gemcitabine and cisplatin/carboplatin-based chemotherapy in association with Glutathione S-transferase (GSTs) gene polymorphism. Material and Methods: A total of 216 histologically confirmed cases of gallbladder cancer were recruited. A total of 180 patients were treated with gemcitabine and cisplatin/carboplatin-based chemotherapy. GSTM1, GSTT1, and GSTP1 genotypes were determined by multiplex PCR and by PCR restriction fragment length polymorphism (PCR-RFLP), respectively. The influence of genetic polymorphism on overall survival was analyzed by Kaplan–Meier method, survival rate difference was analyzed by log-rank test, and hazard ratio for mortality outcomes was estimated using Cox regression method. Results: GBC patients having genotype GSTP1 ( AG + GG ) showed poor 3-year survival rate of 0.8% compared to 10.9% of GSTP1 ( AA ) genotype (χ 2 = 6.456, P = 0.011). The multivariate Cox regression results showed that the death risk was significantly higher in GSTP1 (AG + GG) genotype (HR = 3.858, P = 0.050). We found no association of GSTM1 and GSTT1 gene polymorphism with the survival; however, the combined genotypes of GSM1/GSTP1, GSTT1/GSTP1, and GSTM1/GSTT1/GSTP1 were associated with survival ( P = 0.053, 0.006, and 0.058, respectively). Increased death hazard was noted by the genotype combinations of GSTM1+/GSTP1AG + GG (HR = 3.484, P = 0.024), GSTM1-/GSTP1AG + GG (HR = 2.721, P = 0.014), GSTT1+/GSTP1AG + GG (HR = 20.690, P = 0.001), and GSTT1-/GSTP1AA (HR = 26.111, P < 0.0001). Our findings indicate that chemotherapy treatment response of GSTP1 (AG + GG ) has 1.62-fold increased risk for progression compared to GSTP1 (AA ) genotype (p = 0.018); however, none of the genotypes showed association with overall survival and death risk after chemotherapeutic treatment. Conclusion: We found that the presence of GSTP1 ( AG + GG) genotype showed survival disadvantage and poor treatment outcomes in response to gemcitabine and cisplatin/carboplatin-based chemotherapy. This could serve as biomarker, and future research in pharmacogenomics will definitely pave the way for the development of better treatment approach for GBC.

Phospholipids are the fundamental component of biological membranes present in all living cells. Phospholipases are the lipolytic enzymes that hydrolyze particular ester linkages in phospholipids and produce a variety of bioactive lipid mediators including diacylglycerol, phosphatidic acid, lysophosphatidic acid, and arachidonic acid (AA). Phospholipases like phospholipases (A1 and A2), phospholipases C, and phospholipases D are important intercellular and intracellular signaling mediators that have a wide range of structures, functions, and mechanisms in cancer biology. Multiple cellular activities (proliferation, migration, invasion, and angiogenesis) that promote cancers are regulated by several lipid mediators. Mechanisms of individual phospholipases, by which these influence cancer-related cellular activities and the interplay between them, have been investigated by researchers. Choline kinase, phosphatidylcholine-specific phospholipase D1, phosphatidylcholine-specific phospholipase C, sphingomyelinases, choline transporters, phosphodiesterases, phosphatidylethanolamine, N-methyltransferase, and ethanolamine kinase are the significant phospholipases in carcinogenesis. These enzymes are attributed to oncogenic transformation, tumor growth, and critical cancer cell characteristics such as fast proliferation, migration, and invasion. This chapter aims to explore the current understanding of phospholipase categorization and mechanism in cancer biology. The present literature also discusses potential mechanistic and therapeutic targets.

Stem cells' self-renewal and multi-lineage differentiation are regulated by a complex network consisting of signaling factors, chromatin regulators, transcription factors, and non-coding RNAs (ncRNAs). Diverse role of ncRNAs in stem cell development and maintenance of bone homeostasis have been discovered recently. The ncRNAs, such as long non-coding RNAs, micro RNAs, circular RNAs, small interfering RNA, Piwi-interacting RNAs, etc., are not translated into proteins but act as essential epigenetic regulators in stem cells' self-renewal and differentiation. Different signaling pathways are monitored efficiently by the differential expression of ncRNAs, which function as regulatory elements in determining the fate of stem cells. In addition, several species of ncRNAs could serve as potential molecular biomarkers in early diagnosis of bone diseases, including osteoporosis, osteoarthritis, and bone cancers, ultimately leading to the development of new therapeutic strategies. This review aims to explore the specific roles of ncRNAs and their effective molecular mechanisms in the growth and development of stem cells, and in the regulation of osteoblast and osteoclast activities. Furthermore, we focus on and explore the association of altered ncRNA expression with stem cells and bone turnover.

Metabolic reprogramming enables cancer cells to proliferate and produce tumor biomass under a nutrient-deficient microenvironment and the stress of metabolic waste. A cancer cell adeptly undergoes a variety of adaptations in metabolic pathways and differential expression of metabolic enzyme genes. Metabolic adaptation is mainly determined by the physiological demands of the cancer cell of origin and the host tissue. Numerous metabolic regulators that assist cancer cell proliferation include uncontrolled anabolism/catabolism of glucose metabolism, fatty acids, amino acids metabolism, nucleotide metabolism, tumor suppressor genes, microRNAs, and many regulatory enzymes and genes. Using this paradigm, we review the current understanding of metabolic reprogramming in tumors and discuss the new strategies of cancer metabolomics that can be tapped into for cancer therapeutics.

Abstract Background: In India, nicotine addiction causes a huge socio-economic burden, mortality, and morbidity. Chronic intake develops a variety of symptoms and life-long medical complications. The study aims to examine the nicotine-induced effects on cellular oxidative stress and psychological stress and its correlations with homocysteine (Hcy) concentration in nicotine-addicted respondents. Methods & Results: Nicotine-induced psychological stress was assessed through perceived stress scales (PSS) and coping self-efficacy (CSE) scales and oxidative stress was estimated through the markers- Malondialdehyde (MDA), superoxide dismutase (SOD), and Catalase. We found significantly higher (p=0.0001) perceived stress (PS) with diminished CSE in addicted respondents whereas low PS with significantly increased (p=0.0001) CSE were observed in non-addicted. In erythrocytes (RBCs), MDA content was found significantly increased (p=0.0006) in the nicotine-addicted group that may cause oxidative damage. SOD activity was significantly decreased (p=0.0001) in the addicted group. Similarly, plasma Catalase activity was also decreased (p=0.02). Nicotine intake influences Hcy concentration, by 55%, 27.5%, and 7.5% in addicted respondents categorized as moderate, intermediate, and severe Hcy categories. Conclusions: The minimal short-term nicotine consumption has the antioxidant role that promotes positive stimulus on memory and triggers executive functions but the same gets impaired and mitigated on chronic exposure. Chronic nicotine consumption induces oxidative stress and perceived psychological stress as well as influences the Homocysteine concentration in the addicted individuals. Higher oxidative stress impairs cellular defensive mechanisms and causes the risk for severe damage to cells and tissues.

Background: The minimal short-term nicotine consumption has the antioxidant role that promotes positive stimulus on memory and triggers executive functions, but the same gets impaired and mitigated on chronic exposure. The study examines the nicotine-induced effects on cellular oxidative stress and psychological stress and correlations with Homocysteine (Hcy) concentration in nicotine-addicted respondents. Methods: Nicotine-induced psychological stress was assessed through perceived stress scales (PSS), and coping self-efficacy (CSE) scales, and oxidative stress was measured through the markers- Malondialdehyde (MDA), superoxide dismutase (SOD), and Catalase. Results: We found significantly higher (p=0.0001) perceived stress (PS) with diminished CSE in addicted respondents, whereas low PS with significantly increased (p=0.0001) CSE were observed in non-addicted. In erythrocytes (RBCs), MDA content was found significantly increase (p=0.0006) in the nicotine-addicted group, which may cause oxidative damage. SOD activity was significantly decreased (p=0.0001) in the addicted group. Similarly, plasma Catalase activity was also decreased (p=0.02). Nicotine intake influences Hcy concentration by 55%, 27.5%, and 7.5% in addicted respondents categorized as moderate, intermediate, and severe Hcy categories. Conclusions: Chronic nicotine consumption induces oxidative stress and perceived psychological stress as well as influences the Hcy concentration in nicotine-consuming individuals. Increased psychological stress stimulates oxidative stress that impairs cellular defensive mechanisms.Funding Information: The authors declare that no funds, grants, or other financial support were received during research and manuscript preparation. The NIH 1R15CA252997-01A1 grant supports research in the GCS lab.Declaration of Interests: The authors declared no potential conflicts of interest concerning this article's research, authorship, and publication. The authors have no financial or non-financial interest to disclose.Ethics Approval Statement: The study has been approved by the population resource and research center, institutional ethics committee, Praygaraj, UP, India, with reference number - IERB19/9.42. Informed consent was obtained from all participants individually included in the study.

Context: Lung cancer pathological process involves cumulative effects exerted by gene polymorphism(s), epigenetic modifications, and alterations in DNA repair machinery. Further, DNA damage due to oxidative stress, chronic inflammation, and the interplay between genetic and environmental factors is also an etiologic milieu of this malignant disease. Aims: The present study aims to assess the prognostic value of DNA repair, cytokines, and GST gene polymorphism in lung cancer patients who had not received any neoadjuvant therapy. Materials and Methods: In this case–control study, 127 cases and 120 controls were enrolled. DNA from the blood samples of both patients and controls was used to genotype XRCC1Arg399Gln, XPDLys751Gln, and interleukin-1 (IL-1β) genes by polymerase chain reaction (PCR)-restriction fragment length polymorphism method, whereas multiplex PCR was performed to genotype GSTT1 and GSTM1. Results: Binary logistic regression analysis showed that XRCC1Arg399Gln-mutant genotype (Gln/Gln, odds ratio [OR] = 4.6, 95% confidence interval [CI]: 2.2–9.6) and GSTT1 null (OR = 2.7, 95% CI: 1.6–4.5) were linked to cancer susceptibility. Generalized multidimensional reduction analysis of higher order gene–gene interaction using cross-validation testing (CVT) accuracy showed that GSTT1 (CVT 0.62, P = 0.001), XPD751 and IL-1β (CVT 0.6, P = 0.001), and XRCC1399, XPD751, and interleukin-1 receptor antagonists (IL-1RN) (CVT 0.98, P = 0.001) were single-, two-, and three-factor best model predicted, respectively, for lung cancer risk. Classification and regression tree analysis results showed that terminal nodes which contain XRCC1399-mutant genotype (AA) had increased the risk to lung cancer. Conclusion: The present study demonstrated that XRCC1399 (Gln/Gln), GSTT1, and IL-1RN allele I, I/II served as the risk genotypes. These genes could serve as the biomarkers to predict lung cancer risk.

Oral cancers constitute the majority of head and neck tumors, with a relatively high incidence and poor survival rate in developing countries. While the five-year survival rates of the oral cancer patients have increased to 65%, the overall survival for advanced stages has been at 27% for the past ten years, emphasizing the necessity for further understanding the etiology of the disease, diagnosis, and formulating possible novel treatment regimens. MicroRNAs (miRNAs), a family of small non-coding RNA, have emerged as master modulators of gene expression in various cellular and biological process. Aberrant expression of these dynamic molecules has been associated with many human diseases, including oral cancers. The deregulated miRNAs have been shown to control various oncogenic processes, including sustaining proliferative signaling, evading growth suppressors, resisting cell death activating invasion and metastasis, and inducing angiogenesis. Hence, the aberrant expression of miRNAs associated with oral cancers, makes them potential candidates for the investigation of functional markers, which will aid in the differential diagnosis, prognosis, and development of novel therapeutic regimens. This review presents a holistic insight into our understanding of the role of miRNAs in regulating various hallmarks of oral tumorigenesis.

Visual representation of anatomy, structure and physiology of our internal body forms a basis for therapeutic industry and medical research. Despite technological advancement in the medical field still the diagnosis of complex disease like cancer at its onset remains a major challenge. Rapid evolution in the biomedical sciences such as medical physics and nuclear medicine resulted in various non-invasive imaging techniques. This letter to editor discusses the significance, challenges and future of it. Imaging is a powerful non-invasive diagnostic tool which benefits the physicians and other healthcare professionals and it is constantly evolving towards the goal of precision-/personalized-medicine.