Biomarkers of Oxidative Stress Tethered to Cardiovascular Diseases.

Cardiovascular disease (CVD) is a broad term that incorporated a group of conditions that affect the blood vessels and the heart. CVD is a foremost cause of fatalities around the world. Multiple pathophysiological mechanisms are involved in CVD; however, oxidative stress plays a vital role in generating reactive oxygen species (ROS). Oxidative stress occurs when the concentration of oxidants exceeds the potency of antioxidants within the body while producing reactive nitrogen species (RNS). ROS generated by oxidative stress disrupts cell signaling, DNA damage, lipids, and proteins, thereby resulting in inflammation and apoptosis. Mitochondria is the primary source of ROS production within cells. Increased ROS production reduces nitric oxide (NO) bioavailability, which elevates vasoconstriction within the arteries and contributes to the development of hypertension. ROS production has also been linked to the development of atherosclerotic plaque. Antioxidants can decrease oxidative stress in the body; however, various therapeutic drugs have been designed to treat oxidative stress damage due to CVD. The present review provides a detailed narrative of the oxidative stress and ROS generation with a primary focus on the oxidative stress biomarker and its association with CVD. We have also discussed the complex relationship between inflammation and endothelial dysfunction in CVD as well as oxidative stress-induced obesity in CVD. Finally, we discussed the role of antioxidants in reducing oxidative stress in CVD.

Interleukin-6 gene -174G>C promoter polymorphism reduces the risk of periodontitis in Brazilian populations: A meta-analysis.

INTRODUCTION: Periodontitis is a multifactorial host-mediated oral disease caused by microbes. Previous studies suggested that interleukin-6 (IL-6) gene promoter polymorphism (-174G > C) are associated with the risk of periodontitis, although the results were inconclusive. This study investigated the association between IL-6 -174G > C polymorphism and susceptibility to periodontitis. METHOD: A comprehensive search was conducted in PubMed, EMBASE, Web of Science, and Google Scholar databases to retrieve relevant studies. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to assess the strength of the association between 174G > C polymorphism and the risk of periodontitis. Cochrane Q and I2 statistics were used to measure heterogeneity between studies. Publication bias was estimated using Begg's funnel plots and Egger's test. RESULTS: Our results showed significant differences in the allelic (C vs. G: OR = 0.82, CI = 0.65-1.03), recessive (CC vs. GC + GG: OR = 0.69, CI = 0.42-1.13), and dominant (GC + CC vs. GG: OR = 0.85, CI = 0.63-1.13) genetic models of the IL6 -174G > C polymorphism and risk of periodontitis. Further, subgroup analysis showed decreased susceptibility to periodontitis associated with IL6 -174 G > C in a Brazilian population (C vs. G: OR = 0.60, CI = 0.41-0.88; GC + CC vs. GG: OR = 0.57, CI = 0.42-0.78) but not in Asian or Caucasian populations. CONCLUSION: The findings of this study revealed that the IL6 -174 "C" allele is protective against periodontitis in the Brazilian population.

A Retrospective Look at Anti-EGFR Agents in Pancreatic Cancer Therapy.

BACKGROUND: The introduction of Monoclonal Antibodies (mAbs) and small-molecule Tyrosine Kinase Inhibitors (TKIs) that target the Epidermal Growth Factor Receptor (EGFR), marks a huge step forward in the Pancreatic Cancer (PC) therapy. However, anti-EGFR therapy is found to be successful only in a fraction of patients. Although anti-EGFR agents have shown considerable clinical promise, a serious adverse event associated with anti- EGFR therapy has been challenging. At this juncture, there is still more to be done in the search for effective predictive markers with therapeutic applicability. METHODS: A focused literature search was conducted to summarize the existing evidence on anti-EGFR agents in pancreatic cancer therapy. RESULTS: This review discusses various anti-EGFR agents currently in use for PC therapy and potential adverse effects associated with it. Existing evidence on EGFR TKIs demonstrated better tolerant effects and outcomes with multiple toxic regimens. Anti-EGFR therapy in combination with chemotherapy is necessary to achieve the best clinical outcomes. CONCLUSION: Future prospective studies on the identification of additional biological agents and novel anti-EGFR agents are warranted.

Nanoparticles in Pancreatic Cancer Imaging and Therapy.

Pancreatic cancer (PC) is the fourth leading cause of cancer deaths in both men and women. Because most PC patients are initially diagnosed at an advanced stage of disease, effective diagnostic tests for earlier diagnosis of PC are needed. Several studies have investigated the utility of nanoparticle for both diagnosis and therapy of PC. This review discusses the various engineered nanoparticles currently in use for imaging and therapy. Although nanoparticles have shown considerable clinical promise, complete translation of nanoparticle-based molecular imaging and oncotherapeutic agents has been the challenge.

Small molecule tyrosine kinase inhibitors and pancreatic cancer-Trials and troubles.

Pancreatic cancer (PC) is an aggressive carcinoma and the fourth cause of cancer deaths in Western countries. Although surgery is the most effective therapeutic option for PC, the management of unresectable, locally advanced disease is highly challenging. Our improved understanding of pancreatic tumor biology and associated pathways has led to the development of various treatment modalities that can control the metastatic spread of PC. This review intends to present trials of small molecule tyrosine kinase inhibitors (TKIs) in PC management and the troubles encountered due to inevitable acquired resistance to TKIs.

Pain Management Issues as Part of the Comprehensive Care of Patients with Sickle Cell Disease.

BACKGROUND: Vaso-occlusive pain crisis is one of the primary complications of sickle cell disease (SCD) and is responsible for the majority of hospital visits in patients with SCD. Stints of severe pain can last for hours to days and are difficult to treat and manage, often resulting in drastically reduced quality of life. PURPOSE: Our purpose is to provide an overview of pain management issues in SCD populations. METHODS: We explored literature using PubMed and Embase for the etiology and management of pain in SCD. Databases were searched employing the following terms: sickle cell, pain pathways, pain perception, pharmacological therapies, psychological therapies, physical therapies and genetics. RESULTS: Pain in SCD can vary from acute to chronic (persistent) or mixed and understanding of the underlying mechanisms is important for proper pain management. Currently, there are many means of managing pain in children with SCD, which involve pharmacological and non-pharmacological approaches. A combination of psychotherapy and pain medications can be used for treatment of pain and other psychosocial co-morbidities in complex persistent pain. CONCLUSIONS: Providing more appropriate medication and optimal dosage based on individual's genomic variations is the future of medicine, and this will allow the physicians to hone in on optimal pain management in patients with SCD.

CBS c.844ins68 Polymorphism Frequencies in Control Populations: Implications on Nonsyndromic Cleft Lip With or Without Cleft Palate.

INTRODUCTION: Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect with substantial clinical and social impact. Folate deficiency is one of the factors that have been associated with increased risk for NSCLP. Polymorphisms in folate and homocysteine pathway genes may act as susceptibility factors. OBJECTIVE: The objective of this study was to evaluate prevalence estimates of cystathionine beta-synthase (CBS) insertion of 68-bp (c.844ins68) polymorphisms and their correlation with NSCLP. MATERIAL AND METHODS: A total of 236 unrelated individuals from seven Indian populations and an additional 355 cases with NSCLP and 357 controls without NSCLP were included in this study. We investigated the CBS c.844ins68 polymorphism in all samples. Genotyping was performed with polymerase chain reaction and electrophoresis. The data were statistically analyzed using the chi-square test. RESULTS: The CBS c.844ins68 allele is present in six of the seven populations analyzed, and allele frequencies range from 1.5% in Balija to 9.1% in Sugali populations. The CBS c.844ins68 polymorphism showed a significant protective effect on NSCLP at both genotype (WW versus WI: odds ratio [OR] = 0.54, 95% confidence interval [CI] = 0.31 to 0.95, P = .149) and allele levels (W versus I: OR = 0.56, 95% CI = 0.32 to 0.96, P = .033). CONCLUSIONS: The current study observed significant differences in the frequency of the CBS 844ins68 allele across populations. There is a significant association between CBS c.844ins68 polymorphism and cleft lip and palate in the Indian population. Additional studies are warranted to identify the functional variants in the genes controlling homocysteine as etiological contributors to the formation of oral clefts.

NAT2 genetic variations among South Indian populations.

The N-acetyltransferases (NATs) are xenobiotic-metabolizing enzymes involved in the metabolism of drugs, environmental toxins and the aromatic amine carcinogens present in cigarette smoke. Genetic variations in NAT2 have long been recognized as the cause of variable enzymatic activity or stability, leading to slow or rapid acetylation. In the present study, we genotyped three single-nucleotide polymorphisms (SNPs) from the NAT2 gene (rs1799929, rs1799930 and rs1799931), using TaqMan allelic discrimination, among 212 individuals from six major South Indian populations and compared the results with other available Indian and worldwide data. All three of the markers followed Hardy-Weinberg equilibrium and were highly polymorphic in the studied populations. The constructed haplotypes showed a high level of heterozygosity. All of the populations in the present study commonly shared only four haplotypes out of the eight possible three-site haplotypes. The haplotypes exhibited fairly high frequencies across multiple populations, where three haplotypes were shared by all six populations with a cumulative frequency ranging from 88.2% (Madiga) to 97.0% (Balija). We also observed a tribal-specific haplotype. A strong linkage disequilibrium (LD) between rs1799929 and rs1799930 was consistent in all of the studied populations, with the exception of the Madiga. A comparison of the genomic regions 20-kb up- and downstream of rs1799930 in a large number of worldwide samples showed a strong LD of this SNP with another NAT2 SNP, rs1112005, among the majority of the populations. Moreover, our lifestyle test (hunter-gatherer versus agriculturist) in comparison with the NAT2 variant suggested that two of the studied populations (Balija and Madiga) have likely shifted their diet more recently.

Functional PstI/RsaI polymorphisms in the CYP2E1 gene among south Indian populations.

Human cytochrome P4502E1 (CYP2E1) is a well-conserved xenobiotic-metabolizing enzyme expressed in liver, kidney, nasal mucosa, brain, lung, and other tissues. CYP2E1 is inducible by ethanol, acetone, and other low-molecular weight substrates and may mediate development of chemically-mediated cancers. CYP2E1 polymorphisms alter the transcriptional activity of the gene. This study was conducted in order to investigate the allele frequency variation in different populations of Andhra Pradesh. Two hundred and twelve subjects belonging to six populations were studied. Genotype and allele frequency were assessed through TaqMan allelic discrimination (rs6413419) and polymerase chain reaction-sequencing (-1295G>C and -1055C>T) after DNA isolation from peripheral leukocytes. The data were compared with other available world populations. The SNP rs6413419 is monomorphic in the present study, -1295G>C and -1055C>T are less polymorphic and followed Hardy-Weinberg equilibrium in all the populations studied. The -1295G>C and -1055C>T frequencies were similar and acted as surrogates in all the populations. Analysis of HapMap populations data revealed no significant LD between these markers in all the populations. Low frequency of CYP2E1 c2 could be useful in the understanding of south Indian population gene composition, alcohol metabolism, and alcoholic liver disease development. However, screening of additional populations and further association studies are necessary. The heterogeneity of Indian population as evidenced by the different distribution of CYP2E1 c2 may help in understanding the population genetic and evolutionary aspects of this gene.