Mitochondrial Epigenetics Regulating Inflammation in Cancer and Aging.

Inflammation is a defining factor in disease progression; epigenetic modifications of this first line of defence pathway can affect many physiological and pathological conditions, like aging and tumorigenesis. Inflammageing, one of the hallmarks of aging, represents a chronic, low key but a persistent inflammatory state. Oxidative stress, alterations in mitochondrial DNA (mtDNA) copy number and mis-localized extra-mitochondrial mtDNA are suggested to directly induce various immune response pathways.

Role of stress granules in modulating senescence and promoting cancer progression: Special emphasis on glioma.

Stress granules (SGs) contain mRNAs and proteins stalled in translation during stress; these are increasingly being implicated in diseases, including neurological disorders and cancer. The dysregulated assembly, persistence, disassembly and clearance of SGs contribute to the process of senescence. Senescence has long been a mysterious player in cellular physiology and associated diseases.

Loss of tumor susceptibility gene 101 (TSG101) perturbs endoplasmic reticulum structure and function.

Tumor susceptibility gene 101 (TSG101), an ESCRT-I protein, is implicated in multiple cellular processes and its functional depletion can lead to blocked lysosomal degradation, cell cycle arrest, demyelination and neurodegeneration. Here, we show that loss of TSG101 results in endoplasmic reticulum (ER) stress and this causes ER membrane remodelling (EMR). This correlates with an expansion of ER, increased vacuolation, altered relative distribution of the rough and smooth ER and disruption of three-way junctions.

Cytosolic aggregates in presence of non-translocated proteins perturb endoplasmic reticulum structure and dynamics.

Presence of cytosolic protein aggregates and membrane damage are two common attributes of neurodegenerative diseases. These aggregates delay degradation of non-translocated protein precursors leading to their persistence and accumulation in the cytosol. Here, we find that cells with intracellular protein aggregates (of cytosolic prion protein or huntingtin) destabilize the endoplasmic reticulum (ER) morphology and dynamics when non-translocated protein load is high.

Evaluatıon of health effects, genetıc damage and telomere length ın children exposed to arsenic in West Bengal, İndia.

Increasing evidence of arsenic contamination in ground water and its associated adverse health outcomes affects millions of people worldwide. However, arsenic toxicity studies in children have gained impetus very recently due to the non-prominence of the hallmarks of arsenic toxicity i.e skin lesions.

Substantial Evidences Indicate That Inorganic Arsenic Is a Genotoxic Carcinogen: a Review.

Arsenic is one of the most toxic environmental toxicants. More than 150 million people worldwide are exposed to arsenic through ground water contamination. It is an exclusive human carcinogen.

Role of microRNAs in senescence and its contribution to peripheral neuropathy in the arsenic exposed population of West Bengal, India.

Arsenic induced senescence (AIS) has been identified in the population of West Bengal, India very recently. Also there is a high incidence of arsenic induced peripheral neuropathy (PN) throughout India. However, the epigenetic regulation of AIS and its contribution in arsenic induced PN remains unexplored.

Arsenic exposure through drinking water leads to senescence and alteration of telomere length in humans: A case-control study in West Bengal, India.

Arsenic (As) induces pre-malignant and malignant dermatological lesions, non-dermatological health effects and cancers in humans. Senescence involves telomere length changes and acquisition of senescence-associated secretory phenotype (SASP), which promotes carcinogenesis. Though in vitro studies have shown that As induces senescence, population based studies are lacking.

Human urothelial micronucleus assay to assess genotoxic recovery by reduction of arsenic in drinking water: a cohort study in West Bengal, India.

Chronic exposure to arsenic through drinking water affects nearly 26 million individuals in West Bengal, India. Cytogenetic biomarkers like urothelial micronucleus (MN) are extensively used to monitor arsenic exposed population. In 2004-2005, 145 arsenic exposed individuals and 60 unexposed controls were surveyed of which 128 exposed individuals and 54 unexposed controls could be followed up in 2010-2011.

Association of NALP2 polymorphism with arsenic induced skin lesions and other health effects.

Prolonged consumption of arsenic-laden water above the threshold limit of 10μg/L causes a plethora of dermatological and non-dermatological multi-organ health problems, including cancer and death. Among several mechanisms of arsenic-induced toxicity and carcinogenicity studied so far, role of arsenic in impairment of immune system is less understood. Epidemiological data, animal model as well as cell line based studies have indicated that arsenic targets immune system and is associated with characteristic immunosupression, which may further adversely affect respiratory function.

Systems biology approaches to evaluate arsenic toxicity and carcinogenicity: an overview.

Long term exposure to arsenic, either through groundwater, food stuff or occupational sources, results in a plethora of dermatological and non-dermatological health effects including multi-organ cancer and early mortality. Several epidemiological studies, across the globe have reported arsenic-induced health effects and cancerous outcomes; but the prevalence of such diseases varies depending on environmental factors (geographical location, exposure level), and genetic makeup (and variants thereof); which is further modulated by several other factors like ethnicity, age-sex, smoking status, diet, etc. It is also interesting to note that, chronic arsenic exposure to a similar extent, even among the same family members, result in wide inter-individual variations.

Arsenic exposure through drinking water increases the risk of liver and cardiovascular diseases in the population of West Bengal, India.

Background: Arsenic is a natural drinking water contaminant affecting 26 million people in West Bengal, India. Chronic arsenic exposure causes cancer, cardiovascular disease, liver disease, neuropathies and ocular diseases. The aims of the present study were to assess bioindicators of hepatocellular injury as indicated by the levels of liver enzymes, to determine the auto immune status, as indicated by the amounts of anti-nuclear antibodies (ANA) and anti-dsDNA antibodies in their serum, and to predict cardiovascular risk in the arsenic exposed population.