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

Role of skin prick test in allergic disorders: A prospective study in Kashmiri population in light of review

Background: Skin prick test (SPT) is the most effective diagnostic test to detect IgE mediated type I allergic reactions like allergic rhinitis, atopic asthma, acute urticaria, food allergy etc. SPTs are done to know allergic sensitivity and applied for devising immunotherapy as the therapeutic modality. Materials and Methods: This prospective study was conducted in the department of Immunology and Molecular medicine at SKIMS. A total of 400 patients suffering from allergic rhinitis, asthma and urticaria were recruited in this study. SPT was performed with panel of allergens including house dust mite, pollens, fungi, dusts, cockroach, sheep wool and dog epithelia. Allergen immunotherapy was given to allergic rhinitis and asthmatic patients as therapeutic modality. Results: In our study, age of patients ranged from 6 to 65 years. Majority of patients were in the age group of 20-30 years (72%) with Male to female ratio of 1:1.5. Of the 400 patients, 248 (62%) had urticaria, 108 (27%) patients had allergic rhinitis and 44 (11%) patients had asthma. SPT reaction was positive in 38 (86.4%) with allergic asthma, 74 (68.5%) patients with allergic rhinitis and 4 (1.6%) patient with urticaria, respectively. Allergen immunotherapy was effective in 58% patients with allergic rhinitis and 42% allergic asthma. Conclusion: Identifiable aeroallergen could be detected in 86.4% allergic asthma and 68.5% allergic rhinitis patients by SPT alone. Pollens were the most prevalent causative allergen. There was significant relief in the severity of symptoms, medication intake with the help of allergen immunotherapy

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

Knowledge, awareness and attitude towards breast cancer: Risk factors, signs and screening among Health and Allied students: A prospective study

Introduction: Breast cancer (BC) is the second most common cancer in Saudi women. Therefore, understanding BC and its related risk factors, symptoms, and screening is critical for early detection and intervention. The current study was meant to explore the knowledge, awareness, and attitude (KAA) gap in BC: risk factors, symptoms, and screening. Material and Methods: This cross-sectional investigation was carried out with Health Professions Students (HPS) using a predesigned and validated study questionnaire to examine HPS knowledge and attitudes concerning BC and associated risk factors, symptoms, and screening. Results: A total of 277 female students responded to the survey. The frequency of correct answers for the BC knowledge questions varied from the lowest of 27.8% to the highest of 88.8%, with only 5 out of 15 questions (33.3%) answered correctly by more than 60% of the participants, displaying poor knowledge and awareness of BC. A majority (>60%) of the participants identified only 7 of the 18 risk factors of BC correctly, whereas 11 of the 13 early warning signs of BC were identified correctly by the majority (>60%) of the participants. Among the participants, only 26.4% were aware of the breast cancer screening center, but 94.6% of them agreed that early detection of breast cancer is important and 82.7% agreed to participate in the screening program if offered. Conclusion: Participants’ knowledge and awareness of BC were found to be relatively low; however, their attitudes towards BC screening were positive. As a result, it is critical to develop effective education programs, curricular activities, and awareness campaigns to address the lack of awareness of BC and to have an appropriate response to screening to reduce disease burden

Chronic urticaria merits serum vitamin D evaluation and supplementation; a randomized case control study

Background Several studies suggest that Vitamin D (Vit-D3) supplementation reduces Chronic Urticaria (CU) symptoms.Objectives Evaluation of serum 25-hydroxyvitamin-D (25 (OH)2D) level and assessment of therapeutic effect of VitD3in CU patients.Methods 192 subjects were stratified according to the baseline 25(OH)2D levels and subsequently randomized into three subgroups to receive Vit-D3 alone (VD) or antihistamine and systemic corticosteroid (H+S) or VitD3 with antihistamine and systemic corticosteroid (VD+H+S) for 6 weeks between July 2012 to Oct 2014. 130 healthy controls (HC) were followed without any intervention. The patients were evaluated for reduction in urticarial symptoms using visual analogue scale (VAS) and 5-D itch score.Results Low serum levels of 25 (OH)2D was observed in 91% of CU patients and 64% of the healthy controls (P < 0.0001). VAS and 5-D Score in subgroups VD, H + S and VD + H + S decreased significantly from 6 · 7 ± 0 · 043, 6 · 6 ± 0 · 42 and 6 · 68 ± 0 · 40 at baseline to 5 · 2 ± 0 · 70 (P = 0 · 0088), 3 · 3 ± 0 · 50 (P < 0 · 0001) and1 · 86 ± 0 · 39 (P < 0 · 0001) after treatment and from 14 · 5 ± 0 · 72, 13 · 9 ± 0 · 77 and 13 · 9 ± 0 · 221 to 12 · 06 ± 1 · 10 (P = 0 · 0072), 8 · 1 ± 1 · 13 (P < 0 · 0001) and 5 · 01 ± 0 · 94 (P < 0 · 0001) respectively.Conclusions CU patients have low serum 25(OH)2D levels and Vit-D3 supplementation in combination with antihistamine and systemic corticosteroid show elevated response in resolving the symptoms of CU. This study also warrants that each subject with CU should be screened for serum 25 (OH)2D levels before starting a treatment. Keywords: 25 (OH) vitamin D, 5-D itch score, Chronic Urticaria, Visual analogue scale, Ig