Evaluation of serum proteome from Indian psoriasis patients.

Psoriasis is a polygenic chronic skin condition, associated with many systemic disorders. Though it is most studied dermatological condition, molecular mechanism leading to its pathogenesis is still unclear. An insight into its proteome may help unrevealing some biomarkers and therapeutic targets. In this study, we carried out mass spectrometry based quantitative proteomic analysis of serum from psoriasis patients by employing Tandem Mass Tags (TMT) approach. We identified 861,887 MS/MS spectra corresponding to 493 proteins. These dysregulated proteins were further classified by Gene Ontology and protein-protein interaction of dys-regulated proteins revealed networks in psoriasis patients.

Receptor for Advanced Glycation End Product, Organ Crosstalk, and Pathomechanism Targets for Comprehensive Molecular Therapeutics in Diabetic Ischemic Stroke.

Diabetes mellitus, a well-established risk factor for stroke, is related to higher mortality and poorer outcomes following the stroke event. Advanced glycation end products(AGEs), their receptors RAGEs, other ligands, and several other processes contribute to the cerebrovascular pathomechanism interaction in the diabetes-ischemic stroke combination. Critical reappraisal of molecular targets and therapeutic agents to mitigate them is required to identify key elements for therapeutic interventions that may improve patient outcomes. This scoping review maps evidence on the key roles of AGEs, RAGEs, other ligands such as Leukotriene B4 (LTB4), High-mobility group box 1 (HMGB1) nuclear protein, brain-kidney-muscle crosstalk, alternate pathomechanisms in neurodegeneration, and cognitive decline related to diabetic ischemic stroke. RAGE, HMGB1, nitric oxide, and polyamine mechanisms are important therapeutic targets, inflicting common consequences of neuroinflammation and oxidative stress. Experimental findings on a number of existing-emerging therapeutic agents and natural compounds against key targets are promising. The lack of large clinical trials with adequate follow-up periods is a gap that requires addressing to validate the emerging therapeutic agents. Five therapeutic components, which include agents to mitigate the AGE-RAGE axis, improved biomarkers for risk stratification, better renal dysfunction management, adjunctive anti-inflammatory-antioxidant therapies, and innovative neuromuscular stimulation for rehabilitation, are identified. A comprehensive therapeutic strategy that features all the identified components is needed for outcome improvement in diabetic stroke patients.

Relevance of Inflammatory Cytokine mRNA Expression of Tumour Necrosis Factor- Alpha (TNF α), Interleukin 17A (IL 17A) and Interleukin 6 (IL 6) in Indian Patients with Psoriasis.

Background: Psoriasis, a chronic, immune-mediated skin disorder, has systemic manifestations as well as an ample negative impact on the quality of life (QOL) of the patient. An abnormal proliferation of keratinocyte and dermal infiltration by immune cells is a characteristic feature. It involves components of both innate and adaptive immunity, and the interaction of T cells with macrophages. Keratinocytes and dendritic cells are mediated by the secreted cytokines. This study was taken up to look into changes at the molecular level that occur during the expression of three cytokines namely tumour necrosis factor-alpha (TNFα), interleukin 17A (IL-17A) and interleukin 6 (IL-6) in Indian patients with psoriasis. Methods: A case-control study was conducted with samples from 15 psoriasis vulgaris patients and 10 healthy control subjects. Clinical parameters were recorded. Blood samples were analysed for peripheral blood messenger ribonucleic acid (mRNA) expression of TNFα, IL-17A and IL-6 using real-time polymerase chain reaction (RT-PCR). Results: The mRNA expression of TNFα, IL-17A and IL-6 in psoriasis patients were increased as compared to that in normal subjects. Conclusions: The elevated levels of Interleukins indicates a systemic inflammatory process that is akin to the cutaneous inflammation. This study indicates that the targeted therapies against these cytokines are likely to be beneficial in Indian psoriasis patients.

Oxidative stress in cervical cancer and its response to chemoradiation.

OBJECTIVES: Cervical cancer (CaCx) is one of the leading causes of cancer-related death among women worldwide, with the great social and economic burden. Diagnoses in early stages can decrease mortality and morbidity rates. This study was conducted to evaluate the status of serum total antioxidant capacity (TAC), and malondialdehyde (MDA) and copper concentrations among patients with CaCx to determine the level of oxidative stress and effect on which of chemoradiation. MATERIALS AND METHODS: Fifty patients with histopathologically proven CaCx who visited the department of oncology & gynaecology and 50 age-matched healthy females were selected for the study. Serum TAC, MDA, and copper were estimated in both study groups. The effect of chemoradiation on these was estimated in patients with CaCx. RESULTS: The mean ± standard deviation age of the patients was 43.98±6.38 years, whereas that of the controls was 31.56±6.84 years. The mean serum copper and MDA concentrations in the patients was significantly higher as compared with the controls, whereas the mean TAC in the patients was reduced when compared with the controls. After chemoradiation, there was a significant increase and decrease in TAC and MDA, respectively, after chemoradiotherapy, whereas the changes in the copper concentrations were insignificant. CONCLUSION: These results suggest that patients with CaCx were in oxidative stress because the oxidative parameters in serum (copper, MDA) were increased and the defensive TAC was decreased in patients with CaCx and chemoradiotherapy improved their anti-oxidant capacity. Further studies are needed to evaluate the concurrent use of antioxidants with chemoradiotherapy for improving the disease prognosis.