CSP7 Protects Alveolar Epithelial Cells by Targeting -Fibrinolytic Pathways During Lung Injuries.

Impaired alveolar epithelial regeneration in patients with idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) is attributed to telomere dysfunction in type II alveolar epithelial cells (ACs). Genetic susceptibility, aging, and toxicant exposures, including tobacco smoke (TS), contribute to telomere dysfunction in ACs. Here we investigated whether improvement of telomere function plays a role in CSP7-mediated protection of ACs against ongoing senescence and apoptosis during bleomycin (BLM)-induced pulmonary fibrosis (PF) as well as alveolar injury caused by chronic TS exposure.

Combustion conditions influence toxicity of flame-generated soot to ocular (ARPE-19) cells.

Soot is a prevalent aerosol found both indoors and outdoors that has several sources, such as natural (e.g., wildfires), civilian (e.

Caveolin-1-derived peptide attenuates cigarette smoke-induced airway and alveolar epithelial injury.

Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease with no effective treatment that can reduce mortality or slow the disease progression. COPD is the third leading cause of global death and is characterized by airflow limitations due to chronic bronchitis and alveolar damage/emphysema. Chronic cigarette smoke (CS) exposure damages airway and alveolar epithelium and remains a major risk factor for the pathogenesis of COPD.

Influences of polycyclic aromatic hydrocarbon on the epigenome toxicity and its applicability in human health risk assessment.

The existence of polycyclic aromatic hydrocarbons (PAHs) in ambient air is an escalating concern worldwide because of their ability to cause cancer and induce permanent changes in the genetic material. Growing evidence implies that during early life-sensitive stages, the risk of progression of acute and chronic diseases depends on epigenetic changes initiated by the influence of environmental cues. Several reports deciphered the relationship between exposure to environmental chemicals and epigenetics, and have known toxicants that alter the epigenetic states.

Reproductive factors and breast cancer risk: A meta-analysis of case-control studies in Indian women.

Background/objective: India is the world's most biodiverse region and is undergoing a period of dramatic social and economic change. Due to population's explosion, climate change and lax implementation of environmental policies, the incidence of breast cancer is increasing. From population-based cancer registry data, breast cancer is the most common cancer in women in urban registries where it constitutes more than 30% of all cancers in females.

Monitoring and Measuring Mammalian Autophagy.

Macroautophagy (autophagy) is a conserved lysosomal-based intracellular degradation pathway. Here, we present different methods used for monitoring autophagy at cellular level. The methods involve Atg8/LC3 detection and quantification by Western blot, autophagic flux measurement through Western blot, direct fluorescence microscopy or indirect immunofluorescence, and finally traffic light assay using tf-LC3-II.

PUMA dependent mitophagy by Abrus agglutinin contributes to apoptosis through ceramide generation.

PUMA, a BH3-only pro-apoptotic Bcl2 family protein, is known to translocate from the cytosol into the mitochondria in order to induce apoptosis. Interestingly, the induction of PUMA by p53 plays a critical role in DNA damage-induced apoptosis. In this study, we reported mitophagy inducing potential of PUMA triggered by phytolectin Abrus agglutinin (AGG) in U87MG glioblastoma cells and established AGG-induced ceramide acts as the chief mediator of mitophagy dependent cell death through activation of both mitochondrial ROS as well as ER stress.

DNA damage by 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced p53-mediated apoptosis through activation of cytochrome P450/aryl hydrocarbon receptor.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD; polycyclic aromatic hydrocarbon) is a persistent and ubiquitous environmental contaminant that causes a wide variety of deleterious effects. In this study, the DNA damage and apoptotic activity induced by TCDD was examined using in silico and in vitro approaches. In silico study showed that conformational changes and energies involved in the binding of TCDD to cytochrome P450 1B1 (CYP1B1) were crucial for its target proteins.

Elimination of dysfunctional mitochondria through mitophagy suppresses benzo[a]pyrene-induced apoptosis.

Mitophagy, a special type of autophagy, plays an important role in the mitochondria quality control and cellular homeostasis. In this study, we examined the molecular mechanism of mitophagy induction with benzo[a]pyrene (B[a]P), a ubiquitous polycyclic aromatic hydrocarbon, which acts as a prosurvival response against apoptotic cell death. Our study showed that B[a]P displayed higher cytotoxicity in autophagy-deficient HaCaT cells as compared to control.

Abrus agglutinin promotes irreparable DNA damage by triggering ROS generation followed by ATM-p73 mediated apoptosis in oral squamous cell carcinoma.

Oral cancer, a type of head and neck cancer, is ranked as one of the top most malignancies in India. Herein, we evaluated the anticancer efficacy of Abrus agglutinin (AGG), a plant lectin, in oral squamous cell carcinoma. AGG selectively inhibited cell growth, and caused cell cycle arrest and mitochondrial apoptosis through a reactive oxygen species (ROS)-mediated ATM-p73 dependent pathway in FaDu cells.

Phytotherapeutic approach: a new hope for polycyclic aromatic hydrocarbons induced cellular disorders, autophagic and apoptotic cell death.

Polycyclic aromatic hydrocarbons (PAHs) comprise the major class of cancer-causing chemicals and are ranked ninth among the chemical compounds threatening to humans. Moreover, interest in PAHs has been mainly due to their genotoxic, teratogenic, mutagenic and carcinogenic property. Polymorphism in cytochrome P450 (CYP450) and aryl hydrocarbon receptor (AhR) has the capacity to convert procarcinogens into carcinogens, which is an imperative factor contributing to individual susceptibility to cancer development.

Implications of cancer stem cells in developing therapeutic resistance in oral cancer.

Conventional therapeutics are often frequented with recurrences, refraction and regimen resistance in oral cavity cancers which are predominantly manifested by cancer stem cells (CSCs). During oncoevolution, cancer cells may undergo structural and functional reprogramming wherein they evolve as highly tolerant CSC phenotypes with greater survival advantages. The CSCs possess inherent and exclusive properties including self-renewal, hierarchical differentiation, and tumorigenicity that serve as the basis of chemo-radio-resistance in oral cancer.

Bacopa monnieri-Induced Protective Autophagy Inhibits Benzo[a]pyrene-Mediated Apoptosis.

Benzo[a]pyrene (B[a]P) is capable of inducing oxidative stress and cellular injuries leading to cell death and associates with a significant risk of cancer development. Prevention of B[a]P-induced cellular toxicity with herbal compound through regulation of mitochondrial oxidative stress might protect cell death and have therapeutic benefit to human health. In this study, we demonstrated the cytoprotective role of Bacopa monnieri (BM) against B[a]P-induced apoptosis through autophagy induction.

Serum starvation induces anti-apoptotic cIAP1 to promote mitophagy through ubiquitination.

Mitophagy is a highly specialised type of autophagy that plays an important role in regulating mitochondrial dynamics and controls cellular quality during stress. In this study, we established that serum starvation led to induction of cellular inhibitor of apoptosis protein-1 (cIAP1), which regulates mitophagy through ubiquitination. Importantly, gain and loss of function of cIAP1 resulted in concomitant alteration in mitophagy confirming the direct implication of cIAP1 in induction of mitophagy.

Mutagenic and genotoxic potential of native air borne particulate matter from industrial area of Rourkela city, Odisha, India.

In this study, we examined potential adverse health effect of particulate matter (PM) collected from industrial areas of Rourkela, Odisha, India. Results indicate that PM in these areas contains benzo[a]pyrene in addition to other unidentified molecules. Ames test revealed the above PM to be highly mutagenic.

Abrus Agglutinin, a type II ribosome inactivating protein inhibits Akt/PH domain to induce endoplasmic reticulum stress mediated autophagy-dependent cell death.

Abrus agglutinin (AGG), a type II ribosome-inactivating protein has been found to induce mitochondrial apoptosis. In the present study, we documented that AGG-mediated Akt dephosphorylation led to ER stress resulting the induction of autophagy-dependent cell death through the canonical pathway in cervical cancer cells. Inhibition of autophagic death with 3-methyladenine (3-MA) and siRNA of Beclin-1 and ATG5 increased AGG-induced apoptosis.

Clinical relevance of autophagic therapy in cancer: Investigating the current trends, challenges, and future prospects.

Oncophagy (cancer-related autophagy) has a complex dual character at different stages of tumor progression. It remains an important clinical problem to unravel the reasons that propel the shift in the role of oncophagy from tumor inhibition to a protective mechanism that shields full-blown malignancy. Most treatment strategies emphasize curbing protective oncophagy while triggering the oncophagy that is lethal to tumor cells.

Autophagy protein Ulk1 promotes mitochondrial apoptosis through reactive oxygen species.

Regardless of rapid progression in the field of autophagy, it remains a challenging task to understand the cross talk with apoptosis. In this study, we overexpressed Ulk1 in HeLa cells and evaluated the apoptosis-inducing potential of the Ulk1 gene in the presence of cisplatin. The gain of function of Ulk1 gene showed a decline in cell viability and colony formation in HeLa cells.

Mechanism of autophagic regulation in carcinogenesis and cancer therapeutics.

Autophagy in cancer is an intensely debated concept in the field of translational research. The dual nature of autophagy implies that it can potentially modulate the pro-survival and pro-death mechanisms in tumor initiation and progression. There is a prospective molecular relationship between defective autophagy and tumorigenesis that involves the accumulation of damaged mitochondria and protein aggregates, which leads to the production of reactive oxygen species (ROS) and ultimately causes DNA damage that can lead to genomic instability.

Antitumor effect of soybean lectin mediated through reactive oxygen species-dependent pathway.

Aims: The present study evaluated the potential role of soybean lectin's (SBL) anticancer effect in vitro in different cancer cell lines and the therapeutic effectiveness in vivo in Dalton's lymphoma (DL) bearing mice model.

Main Methods: The effect of SBL on cell growth and viability was measured using MTT assay in different cancer cells in vitro. Apoptosis, autophagic cell death, DNA-damaging potential and reactive oxygen species (ROS) were analyzed in HeLa cells.