Association of interleukin-18 promoter polymorphism with comorbid conditions of cardiovascular disease

Objectives: Cardiovascular disease (CVD) is one of the most clinically relevant pathologies that remains the largest single contributor to global mortality. It is often associated with more than one comorbid condition, which obscures its clinical outcome. The current study aimed to evaluate the possible association of interleukin-18 (IL-18) promoter polymorphism with comorbid conditions of CVD. Methods: We used case-control comparison of specific genotypes of three clinically relevant IL-18 polymorphism hotspots, viz. −656 T/G (rs1946519), −607C/A (rs1946518), and −137 G/C (rs187238) with commonly associated comorbid conditions of CVD such as diabetes, hypertension, and dyslipidemia. For this study, whole blood of CVD patients and healthy control subjects were collected in a citrate coated/plain tube. The routine biochemical parameters were estimated in each sample, and DNA samples were extracted for PCR amplification for further sequencing of targeted amplicons using Sanger method. Results: The studied biochemical parameters showed a significant increase in CVD patients compared with control individuals. Fasting glucose and glycosylated hemoglobin (HBA1C) showed an increase from 4.82 to 8.6 (p < 0.05) and 4.33 to 8.2 (p < 0.05), respectively. The results showed a statistically significant association with CVD-diabetes and CVD-hypertension group with GG, GC, and CC genotype at IL-18 gene locus, rs187238. On the other hand, the CVD-dyslipidemia group showed a positive association with allele distribution at the same hotspot. In addition, the GG, GT, and TT genotype and G and T allele distribution at rs1946519 locus showed statistically significant association with CVD-diabetes, CVD-hypertension, and CVD-dyslipidemia p compared with control subjects. We also observed a statistically significant association of dyslipidemia with three genotypic combinations viz. (rs1946518 AA, rs1946519 GG, rs187238 GG); (rs1946518 AA, rs1946519 GT, rs187238 GG), and (rs1946518 AA, rs1946519 TT, rs187238 GG). Conclusions: Based on our study, we conclude that IL-18 loci, rs1946519 has a significant association with each studied comorbid condition and can be considered a prognostic marker of CVD and comorbidities. Our results are anticipated to be utilized to launch a significant pharmaco-genomic investigation that could identify patients with comorbidities who are more likely to develop CVD

Phenolic Acids-Mediated Regulation of Molecular Targets in Ovarian Cancer: Current Understanding and Future Perspectives

Cancer is a global health concern with a dynamic rise in occurrence and one of the leading causes of mortality worldwide. Among different types of cancer, ovarian cancer (OC) is the seventh most diagnosed malignant tumor, while among the gynecological malignancies, it ranks third after cervical and uterine cancer and sadly bears the highest mortality and worst prognosis. First-line treatments have included a variety of cytotoxic and synthetic chemotherapeutic medicines, but they have not been particularly effective in extending OC patients’ lives and are associated with side effects, recurrence risk, and drug resistance. Hence, a shift from synthetic to phytochemical-based agents is gaining popularity, and researchers are looking into alternative, cost-effective, and safer chemotherapeutic strategies. Lately, studies on the effectiveness of phenolic acids in ovarian cancer have sparked the scientific community’s interest because of their high bioavailability, safety profile, lesser side effects, and cost-effectiveness. Yet this is a road less explored and critically analyzed and lacks the credibility of the novel findings. Phenolic acids are a significant class of phytochemicals usually considered in the nonflavonoid category. The current review focused on the anticancer potential of phenolic acids with a special emphasis on chemoprevention and treatment of OC. We tried to summarize results from experimental, epidemiological, and clinical studies unraveling the benefits of various phenolic acids (hydroxybenzoic acid and hydroxycinnamic acid) in chemoprevention and as anticancer agents of clinical significance

Biogenic Synthesis of Cu-Mn Bimetallic Nanoparticles Using Pumpkin Seeds Extract and Their Characterization and Anticancer Efficacy

Background: Cancer is a chronic, heterogeneous illness that progresses through a spectrum of devastating clinical manifestations and remains the 2nd leading contributor to global mortality. Current cancer therapeutics display various drawbacks that result in inefficient management. The present study is intended to evaluate the anticancer potential of Cu-Mn bimetallic NPs (CMBNPs) synthesized from pumpkin seed extract against colon adenocarcinoma cancer cell line (HT-29). Methods: The CMBNPs were biosynthesized by continuously stirring an aqueous solution of pumpkin seed extract with CuSO4 and manganese (II) acetate tetrahydrate until a dark green solution was obtained. The characteristic features of biogenic CMBNPs were assessed by UV-visible spectrophotometry (UV-vis), X-ray powder diffraction (XRD), energy-dispersive X-ray (EDX), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). A battery of biological assays, viz. neutral red uptake (NRU) assay, in vitro scratch assay, and comet assay, were performed for anticancer efficacy evaluation. Results: The formation of spherical monodispersed bimetallic nanoparticles with an average size of 50 nm was recorded using TEM. We observed dose-dependent cytotoxicity of CMBNPs in the HT-29 cell line with an IC50 dose of 115.2 µg/mL. On the other hand, CMBNPs did not show significant cytotoxicity against normal cell lines (Vero cells). Furthermore, the treatment of CMBNPs inhibited the migration of cancer cells and caused DNA damage with a significant increase in comet tail length. Conclusions: The results showed substantial anticancer efficacy of CMBNPs against the studied cancer cell line. However, it is advocated that the current work be expanded to different in vitro cancer models so that an in vivo validation could be carried out in the most appropriate cancer model

Link between Cancer and Alzheimer Disease via Oxidative Stress Induced by Nitric Oxide-Dependent Mitochondrial DNA Overproliferation and Deletion

Nitric oxide- (NO-) dependent oxidative stress results in mitochondrial ultrastructural alterations and DNA damage in cases of Alzheimer disease (AD). However, little is known about these pathways in human cancers, especially during the development as well as the progression of primary brain tumors and metastatic colorectal cancer. One of the key features of tumors is the deficiency in tissue energy that accompanies mitochondrial lesions and formation of the hypoxic smaller sized mitochondria with ultrastructural abnormalities. We speculate that mitochondrial involvement may play a significant role in the etiopathogenesis of cancer. Recent studies also demonstrate a potential link between AD and cancer, and anticancer drugs are being explored for the inhibition of AD-like pathology in transgenic mice. Severity of the cancer growth, metastasis, and brain pathology in AD (in animal models that mimic human AD) correlate with the degree of mitochondrial ultrastructural abnormalities. Recent advances in the cell-cycle reentry of the terminally differentiated neuronal cells indicate that NO-dependent mitochondrial abnormal activities and mitotic cell division are not the only important pathogenic factors in pathogenesis of cancer and AD, but open a new window for the development of novel treatment strategies for these devastating diseases

Oxidative Stress Mediated Mitochondrial and Vascular Lesions as Markers in the Pathogenesis of Alzheimer Disease

Mitochondrial dysfunction plausibly underlies the aging-associated brain degeneration. Mitochondria play a pivotal role in cellular bioenergetics and cell-survival. Oxidative stress consequent to chronic hypoperfusion induces mitochondrial damage, which is implicated as the primary cause of cerebrovascular accidents (CVA) mediated Alzheimer\u27s disease (AD). The mitochondrial function deteriorates with aging, and the mitochondrial damage correlates with increased intracellular production of oxidants and pro-oxidants. The prolonged oxidative stress and the resultant hypoperfusion in the brain tissues stimulate the expression of nitric oxide synthase (NOS) enzymes, which further drives the formation of reactive oxygen species (ROS) and reactive nitrogen species (RNS). The ROS and RNS collectively contributes to the dysfunction of the blood-brain barrier (BBB) and damage to the brain parenchymal cells. Delineating the molecular mechanisms of these processes may provide clues for the novel therapeutic targets for CVA and AD patients