Colorectal Cancer & Molecular Mutations and Polymorphism

Colorectal cancer (CRC) is one of the major causes of mortality and morbidity, and is the third most common cancer in men and the second most common cancer in women worldwide. The incidence of CRC shows considerable variation among racially or ethnically defined populations in multiracial/ethnic countries. The tumorigenesis of CRC is either because of the chromosomal instability (CIN) or microsatellite instability (MIN) or involving various proto-oncogenes, tumor suppressor genes and also epigenetic changes in the DNA. In this review I have focused on the mutations and polymorphisms of various important genes of the CIN and MIN pathways which have been implicated in the development of CRC

XPD–The Lynchpin of NER: Molecule, Gene, Polymorphisms, and Role in Colorectal Carcinogenesis

In mammals the bulky DNA adduct lesions known to result in deleterious phenotypes are acted upon and removed from the genomic DNA by nucleotide excision repair (NER) pathway. TFIIH multi-protein complex with its important helicase–Xeroderma Pigmentosum Protein (XPD) serves as the pivotal factor for opening up of the damaged lesion DNA site and carry out the repair process. The initial damage verification step of the TFIIH is in part dependent upon the helicase activity of XPD. Besides, XPD is also actively involved in the initiation steps of transcription and in the regulation of the cell cycle and apoptosis. In this review, we will be exploring the new insights in scientific research on the functioning of the NER pathway, the role of TFIIH as the central complex of NER, the pivotal helicase XPD as the lynchpin of NER and the effects of various single nucleotide polymorphisms (SNPs) of XPD on its functioning and their consequent role in colorectal carcinogenesis

Role of TLR4 gene polymorphisms in the colorectal cancer risk modulation in ethnic Kashmiri population – A case–control study

Background: Colorectal carcinogenesis has been found to be associated with the polymorphic status of Toll-like receptor 4 gene in various populations of the world. Aim: The aim of the study was to determine the genetic association of TLR4 gene polymorphisms (Asp299Gly and Thr399Ile) with disease susceptibility and risk development in colorectal cancer (CRC) patients of Kashmir, India. Materials and methods: Genotype frequencies of TLR4 polymorphisms (Asp299Gly and Thr399Ile) were compared between 120 CRC patients and 200 healthy controls using PCR-RFLP method. Results: We did not find any significant association between the TLR4 gene polymorphisms and the CRC cases (p > 0.05). However CT genotype (Thr399Ile) showed modest elevated risk of the development of CRC [OR = 1.78 95% CI (0.88–3.5)]. Also G allele (AG genotype) of TLR-4 Asp299Gly polymorphism was found to be significantly associated with the male gender (p value = 0.006) and involvement of Nodes (p value = 0.01) whereas, T allele (CT genotype) of Thr399Ile polymorphism showed significant association with the smoking status (p value = 0.03). Conclusion: Our results suggest that TLR4 gene polymorphism is not a key modulator of the risk of developing colorectal cancer in Kashmiri population

Digital Ischemia in an Extreme Preterm Infant Treated with Nitroglycerin Patch

Ischemic limb lesions occasionally occur in neonates admitted to neonatal intensive care units. Known risk factors include the placement of arterial catheters, arterial punctures to obtain blood samples, and the use of vasoactive/vasopressor medications for hypotension. Prolonged peripheral tissue ischemia may result in serious complications, and successful management depends on early detection, proper assessment, and the institution of appropriate intervention. Currently, there is no standard approach for the management of peripheral tissue ischemia in extreme preterm infants. Topical nitroglycerine use is one of the promising options used to manage ischemic limb injuries in neonates, as demonstrated in several case reports. We report a case of digital ischemia in an extreme preterm infant with no clear risk factors except extreme prematurity, which recovered after topical nitroglycerine therapy

Association of IL1 beta gene polymorphism and allograft functions in renal transplant recipients :a case control study from Kashmir Valley

Abstract Background Cytokines have been found to be the important mediators during renal graft outcome. Therefore, we designed this study to investigate the role of recipients’ IL-1 β promoter (−511) and IL-1 β exon-5 (+3954) polymorphisms with the risk of graft outcome. Methodology We enrolled one hundred recipients of living-related renal transplants together with the age and sex matched controls from the healthy population not having any renal abnormality for this study. Genotype frequencies of the IL-1 β promoter (−511) and IL-1 β exon-5 (+3954) were analyzed using PCR-RFLP technique. Results Our results revealed significant differences in the healthy control group and patient group in IL 1β +3954 (p < 0.001). The frequency of variant type TT genotype was higher in RE group as compared to SGF and showed 4 fold risk of rejection (OR = 4.54, p < 0.069) although p value was not significant. The frequency of wild type CC genotype and CT was not significant (p value 0.89 and 0.74 respectively). Conclusion Our findings suggest that there is a prevalence of mutated allele of IL-1 gene cluster in our population, which may be responsible for renal dysfunction

Multi-Therapeutic Potential of Naringenin (4′,5,7-Trihydroxyflavonone): Experimental Evidence and Mechanisms

Extensive research has been carried out during the last few decades, providing a detailed account of thousands of discovered phytochemicals and their biological activities that have the potential to be exploited for a wide variety of medicinal purposes. These phytochemicals, which are pharmacologically important for clinical use, primarily consist of polyphenols, followed by terpenoids and alkaloids. There are numerous published reports indicating the primary role of phytochemicals proven to possess therapeutic potential against several diseases. However, not all phytochemicals possess significant medicinal properties, and only some of them exhibit viable biological effects. Naringenin, a flavanone found in citrus fruits, is known to improve immunity, repair DNA damage, and scavenge free radicals. Despite the very low bioavailability of naringenin, it is known to exhibit various promising biological properties of medicinal importance, including anti-inflammatory and antioxidant activities. This review focuses on the various aspects related to naringenin, particularly its physicochemical, pharmacokinetic, and pharmacodynamic properties. Furthermore, various pharmacological activities of naringenin, such as anticancer, antidiabetic, hepatoprotective, neuroprotective, cardioprotective, nephroprotective, and gastroprotective effects, have been discussed along with their mechanisms of action