Assessment of Lactobacillus rhamnosus mediated protection against arsenic-induced toxicity in zebrafish: a qPCR-based analysis of Firmicutes and Bacteroidetes groups and embryonic development.

Arsenic poses a significant health risk worldwide, impacting the gut microbiota, reproductive health, and development. To address this issue, a cost-effective method like probiotic supplementation could be beneficial. However, the interplay between arsenic toxicity, probiotics, gut microbiota, and maternal transcript modulation remains unexplored. This study investigates the impact of Lactobacillus rhamnosus (L. rhamnosus) DSM 20021 on the proportions of Firmicutes and Bacteroidetes, as well as its effects on embryonic development in zebrafish induced by arsenic trioxide (As2O3). Adult zebrafish were exposed to both high and environmentally relevant concentrations of As2O3 (10, 50, and 500 ppb) for 1, 6, and 12 weeks. qPCR analysis revealed increased proportions of Firmicutes and Bacteroidetes in all As2O3-exposed and As2O3 + L. rhamnosus-exposed groups, while no significant changes were observed in groups exposed only to L. rhamnosus DSM 20021. The larvae, exposed to 500 ppb of As2O3 for 12 weeks, exhibited low growth, decreased survival rates, and morphological deformities. However, these adverse effects were reversed upon exposure to only L. rhamnosus DSM 20021. Furthermore, the expression of DVR1 and ABCC5, which are involved in defense against xenobiotics and embryo development, decreased significantly in As2O3 (500 ppb) and As2O3 (500 ppb) + L. rhamnosus-exposed groups, whereas ameliorative effects were observed in only L. rhamnosus DSM 20021-exposed groups.

Metagenomic Insights into the Gut Microbiota of Eudrilus eugeniae (Kinberg) and Its Potential Roles in Agroecosystem.

Gut microbiomes, a consortium of microorganisms that live in the animal gut, are highly engineered microbial communities. It makes a major contribution to digestive health, metabolism management, and the development of a strong immune system in the host. The present study was taken up to answer the long-running question about the existence of truly indigenous microflora of the epigeic earthworm gut. This is due to the general difficulties of culturing many of the microorganisms found in soil or earthworms' gut. Keeping this fact in a view, the metagenomics approach using 16S rRNA marker gene incorporated with amplicon-based sequencing was used to explore microbiota of commercially overriding, diversely fed epigeic earthworm Eudrilus eugeniae (Kinberg) in three varied habitats viz., artificial soil (AS), organic agricultural farm soil (OAFS) and conventional agriculture farm soil (CAFS). There are predominant bacteria that belong to different phyla such as Proteobacteria (29.72-76.81%), Actinobacteria (11.06-34.42%), Firmicutes (6.02-19.81%), and Bacteroidetes (2.40-9.22%) present in the gut of E. eugeniae. The alpha diversity (Observed species, Chao1, ACE, Shannon, Simpson, and Fisher alpha) indices showed that OAFS had significantly higher alpha diversity than AS and CAFS groups. The core microbiota analysis showed that OAFS and AS groups had a relatively similar bacterial panel in comparison to the CAFS group. Various statistical tools i.e. MetagenomeSeq, LEfSe, and Random Forest analysis were performed and the findings demonstrated prevalence of the most significant bacterial genera; Aeromonas, Gaiella, and Burkholderia in CAFS group. Nonetheless, in AS and OAFS groups, the common existence of Anaerosporobacter and Aquihabitans were found respectively. Metagenomic functional prediction revealed that earthworms' gut microbial communities were actively involved in multiple organic and xenobiotics compound degradation-related pathways. This is the first research to use high-throughput 16S rRNA gene amplicon sequencing to show the gut microbiota of E. eugeniae in diverse agricultural systems. The findings suggest the configuration of the gut microbiota of earthworms and its potential role in the soil ecosystem depends on the microbial communities of the soil.

Reproductive toxic potential of phthalate compounds - State of art review.

Phthalates are pervasive compounds, and due to the ubiquitous usage of phthalates, humans or even children are widely exposed to them. Since phthalates are not chemically bound to the plastic matrix, they can easily leach out to contaminate the peripheral environment. Various animal and human studies have raised vital health concern including developmental and reproductive toxicity of phthalate exposure. The present review is based upon the available literature on phthalates with respect to their reproductive toxic potential. Common reproductive effects such as declined fertility, reduced testis weight, variations in accessory sex organs and several female reproductive disorders appeared to be largely associated with the transitional phthalates. Among the higher molecular weight phthalates (≥ C7), di-isononyl phthalate (DINP) produces some minor effects on development of male reproductive tract and among low molecular weight phthalates (≤C3), di-methyl (DMP) and di-isobutyl (DIBP) phthalate produce some adverse effects on male reproductive system. Whereas transitional phthalates such as di-butyl phthalate, benzyl butyl phthalate, and di-(2-ethylhexyl) phthalate have shown adverse effects on female reproductive system. Owing to these, non-toxic alternatives to phthalates may be developed and use of phthalates could be rationalized as an important issue where human reproduction system is involved. Though, more epidemiological studies are needed to substantiate the reported findings on phthalates.

Genetic engineering of potato (Solanum tuberosum L.) for enhanced α-tocopherols and abiotic stress tolerance.

Vitamin E (α-tocopherol) is a lipid-soluble essential vitamin recognized for improvement in degenerative health conditions, abating cancer risk, and coronary heart diseases in humans. While in plants, it acts as a free radical scavenger that protects cells against oxidative and photooxidative damages. The daily consumption of potato makes it a key target for biofortification with vitamins for eliminating vitamin deficiency in large populations. Vitamin E biosynthetic pathway genes have been overexpressed in plants via genetic engineering to enhance the α-tocopherol content. Major genes involved in the vitamin E biosynthesis in plants viz. the homogentisate-phytyltransferase (At-HPT) and γ-tocopherol-methyltransferase (At-γ-TMT), isolated from Arabidopsis were constitutively overexpressed in potato (Solanum tuberosum L.). The molecular analyses of independent transgenic lines revealed a stable integration of both the genes in the plant genome. The transgenic potato exhibited significantly improved vitamin E contents up to 173-258% in comparison to the untransformed control plants. Transgenic tissues also exhibited increased cellular antioxidant enzymes, proline, osmolyte, and glutathione content that are directly correlated with the ability of the plant to withstand abiotic stresses imposed by salt (NaCl) and heavy metal (CdCl2 ). Therefore, the current strategy of increasing the vitamin E content in potato with enhanced tolerance to abiotic stresses might greatly aid efforts to engineer crops for human health benefits and greater yield under adverse environmental conditions.

Contribution of Vesicular Glutamate Transporters to Stress Response and Related Psychopathologies: Studies in VGluT3 Knockout Mice.

Maintenance of the homeostasis in a constantly changing environment is a fundamental process of life. Disturbances of the homeostatic balance is defined as stress response and is induced by wide variety of challenges called stressors. Being the main excitatory neurotransmitter of the central nervous system glutamate is important in the adaptation process of stress regulating both the catecholaminergic system and the hypothalamic-pituitary-adrenocortical axis. Data are accumulating about the role of different glutamatergic receptors at all levels of these axes, but little is known about the contribution of different vesicular glutamate transporters (VGluT1-3) characterizing the glutamatergic neurons. Here we summarize basic knowledge about VGluTs, their role in physiological regulation of stress adaptation, as well as their contribution to stress-related psychopathology. Most of our knowledge comes from the VGluT3 knockout mice, as VGluT1 and 2 knockouts are not viable. VGluT3 was discovered later than, and is not as widespread as the VGluT1 and 2. It may co-localize with other transmitters, and participate in retrograde signaling; as such its role might be unique. Previous reports using VGluT3 knockout mice showed enhanced anxiety and innate fear compared to wild type. Moreover, these knockout animals had enhanced resting corticotropin-releasing hormone mRNA levels in the hypothalamus and disturbed glucocorticoid stress responses. In conclusion, VGluT3 participates in stress adaptation regulation. The neuroendocrine changes observed in VGluT3 knockout mice may contribute to their anxious, fearful phenotype.

Cancer chemopreventive effects of the flavonoid-rich fraction isolated from papaya seeds.

Intervention to decelerate, arrest, or reverse the process of carcinogenesis by the use of either natural or synthetic agents individually or in combination has emerged as a promising and pragmatic medical approach to reduce cancer risk. In the present study, we examined the cancer chemopreventive potential of a flavonoid-rich fraction isolated from the seeds of Carica papaya, a plant traditionally referred to as papaw. The flavonoid-enriched benzene fraction of the aqueous extract exerted its anticancer properties in vitro through cytoprotection, antioxidative and antiinflammatory mechanisms and genoprotection in response to isocyanate-induced carcinogenicity. Medium-term anticarcinogenicity and 2-stage skin papillomagenesis studies conducted in benzopyrene-induced lung carcinogenesis and 7,12-dimethyl benz(a)anthracene-mediated skin papillomagenesis mouse models further validated our in vitro observations. This is the first demonstration of chemopreventive activities of papaya seed products, however, further studies to understand the subtle targets of intracellular signaling pathways, pharmacological profile and toxicological safety of this bioactive fraction are essential to pave the way for successful clinical translation. Our study supports the inverse association between dietary flavonoid intake and cancer risk.

Cell cycle deregulation by methyl isocyanate: Implications in liver carcinogenesis.

Liver is often exposed to plethora of chemical toxins. Owing to its profound physiological role and central function in metabolism and homeostasis, pertinent succession of cell cycle in liver epithelial cells is of prime importance to maintain cellular proliferation. Although recent evidence has displayed a strong association between exposures to methyl isocyanate (MIC), one of the most toxic isocyanates, and neoplastic transformation, molecular characterization of the longitudinal effects of MIC on cell cycle regulation has never been performed. Here, we sequentially delineated the status of different proteins arbitrating the deregulation of cell cycle in liver epithelial cells treated with MIC. Our data reaffirms the oncogenic capability of MIC with elevated DNA damage response proteins pATM and γ-H2AX, deregulation of DNA damage check point genes CHK1 and CHK2, altered expression of p53 and p21 proteins involved in cell cycle arrest with perturbation in GADD-45 expression in the treated cells. Further, alterations in cyclin A, cyclin E, CDK2 levels along with overexpression of mitotic spindle checkpoints proteins Aurora A/B, centrosomal pericentrin protein, chromosomal aberrations, and loss of Pot1a was observed. Thus, MIC impacts key proteins involved in cell cycle regulation to trigger genomic instability as a possible mechanism of developmental basis of liver carcinogenesis.

Mitochondrial oxidative stress-induced epigenetic modifications in pancreatic epithelial cells.

Emerging studies have linked prooxidative carbamate compound exposures with various human pathologies including pancreatic cancer. In these studies, our aim was to examine mitochondrial oxidative stress-mediated aberrant chromatin responses in human pancreatic ductal epithelial cells. Posttranslational histone modifications, promoter DNA methylation, and micro-RNA (miRNA) expression patterns were evaluated following induction of mitochondrial oxidative stress by N-succinimidyl N-methylcarbamate exposure. In treated cells, perturbation in mitochondrial machinery led to hypermethylation of p16 and smad4 gene promoters and downregulation of respective gene products. Posttranslational histone modifications that include hypoacetylation of acetylated histone (AcH) 3 and AcH4, hypermethylation of monomethylated histone 3 at lysine 9 and trimethylated histone 4 at lysine 20 ubiquitinated histone (uH) 2A/uH2B, and increased phosphorylation of H2AX and H3 were observed in the treated cells. Altered expression of miRNAs denoted possible location of corresponding genes at oxidatively damaged fragile sites. Collectively, our results provide a direct role of mitochondrial oxidative stress-mediated epigenetic imbalance to perturbed genomic integrity in oxygen radical-induced pancreatic injury. Further, identification and characterization of molecular switches that affect these epigenomic signatures and targets thereof will be imperative to understand the complex role of redox-regulatory network in pancreatic milieu.

Impairment of mitochondrial-nuclear cross talk in neutrophils of patients with type 2 diabetes mellitus.

Increased leukocyte apoptosis is intrinsically linked to disease patho-physiology, susceptibility to and severity of infections in type 2 diabetes mellitus (T2DM) patients. A consistent defect in neutrophil function is considered central to this increased risk for infections. Although redox imbalance is considered a potential mediator of these associated complications, detailed molecular evidence in clinical samples remains largely undetected. The study consisted of three groups (n = 50 each) of Asian Indians: early diagnosed diabetic patients, cases with late-onset diabetic complications and age and gender-matched healthy controls. We evaluated mitochondrial oxidative stress, levels of nuclear DNA damage and apoptosis in peripheral blood neutrophils isolated from T2DM patients. We observed that in both early and late diabetic subjects, the HbA1c levels in neutrophils were altered considerably with respect to healthy controls. Increased oxidative stress observed in both early and late diabetics imply the disentanglement of fine equilibrium of mitochondria-nuclear cross talk which eventually effected the augmentation of downstream nuclear γH2AX activation and caspase-3 expression. It would be overly naïve to refute the fact that mitochondrial deregulation in neutrophils perturbs immunological balance in type 2 diabetic conditions. By virtue of our data, we posit that maneuvering mitochondrial function might offer a prospective and viable method to modulate neutrophil function in T2DM. Nevertheless, similar investigations from other ethnic groups in conjunction with experimental evidences would be a preeminent need. Obviously, our study might aid to comprehend this complex interplay between mitochondrial dysfunction and neutrophil homeostasis in T2DM.

Naringenin suppresses aluminum-induced experimental hepato-nephrotoxicity in mice through modulation of oxidative stress and inflammation.

Aluminum is a widely used metal substance in daily life activities that has been shown to cause severe hepato-nephrotoxicity with long-term exposure. Natural dietary flavonoids are being utilized as a newer pharmaceutical approach against various acute and chronic diseases. Naringenin (NAR) has shown efficient therapeutic properties, including effects against metal toxicities. However, the protective efficacy of NAR on aluminum chloride (AlCl3)-induced hepato-renal toxicity needs investigation as aluminum has shown serious environmental toxicity and bioaccumulation behavior. In this study, mice were treated with AlCl3 (10 mg/kg b.w./day) to assess toxicities, and a group of mice were co-treated with NAR (10 mg/kg b.w./day) to assess the protective effects of NAR against hepato-nephrotoxicity. The levels of blood serum enzymes, oxidative stress biomarkers, inflammatory cytokines, and the apoptosis marker caspase-3 were measured using histological examinations. NAR treatment in AlCl3-treated mice resulted in maintained levels of liver and kidney function enzymes and lipid profiles. NAR treatment attenuated oxidative stress by regulating the levels of nitric oxide, advance oxidation of protein products, protein carbonylation, and lipid peroxidation. NAR also replenished reduced antioxidant enzymes such as superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and reduced the levels of glutathione and oxidized glutathione. NAR regulated the levels of pro-inflammatory cytokines (IL-1ß, IL-6, and TNF-α) and elevated the levels of anti-inflammatory cytokines (IL-4, IL-10, and IFN-γ). The histological study further confirmed the protective effects of NAR against AlCl3-induced hepato-renal alterations. NAR decreased the expression of caspase-3 as a mechanism of protective effects against apoptotic damage in the liver and kidney of AlCl3-treated mice. In summary, this study demonstrated the antioxidant and anti-inflammatory properties of NAR, leading to the suppression of AlCl3-triggered hepato-renal apoptosis and histological alterations. The results suggest that aluminum toxicity needs to be monitored in daily life usage, and supplementation of the natural dietary flavonoid naringenin may help maintain liver and kidney health.

Mechanism of action of certain medicinal plants for the treatment of asthma.

ETHNOPHARMACOLOGICAL RELEVANCE: Asthma is often treated and prevented using the pharmacological properties of traditional medicinal plants. These healthcare systems are among the most well-known, conveniently accessible, and economically priced in India and several other Asian countries. Traditional Indian Ayurvedic plants have the potential to be used as phyto-therapeutics, to create novel anti-asthmatic drugs, and as a cost-effective source of pharmaceuticals. Current conventional therapies have drawbacks, including serious side effects and expensive costs that interfere with treatment compliance and affect the patient's quality of life. The primary objective of the article is to comprehensively evaluate the advancement of research on the protective phytochemicals of traditional plants that target immune responses and signaling cascades in inflammatory experimental asthma models. The study would assist in paving the way for the creation of natural phytomedicines that are protective, anti-inflammatory, and immunomodulatory against asthma, which may then be used in individualized asthma therapy. AIM OF THE STUDY: The study demonstrates the mechanisms of action of phytochemicals present in traditional medicinal plants, diminish pulmonary disorder in both in vivo and in vitro models of asthma. MATERIALS AND METHODS: A comprehensive review of the literature on conventional plant-based asthma therapies was performed from 2006 to 2022. The study uses authoritative scientific sources such as PubMed, PubChem Compound, Wiley Online Library, Science Direct, Springer Link, and Google Scholar to collect information on potential phytochemicals and their mechanisms of action. World Flora Online (http://www.worldfloraonline.org) and Plants of the World Online (https://wcsp.science.kew.org) databases were used for the scientific names of medicinal plants. RESULTS: The study outlines the phytochemical mechanisms of some traditional Ayurveda botanicals used to treat asthma. Active phytochemicals including curcumin, withaferin-A, piperine, glabridin, glycyrrhizin, 18ß-glycyrrhetinic acid, trans-cinnamaldehyde, α-hederin, thymoquinone, eugenol, [6]-shogoal, and gingerol may treat asthma by controlling inflammation and airway remodeling. The study concluded that certain Ayurvedic plants' phytochemicals have the ability to reduce inflammation and modulate the immune system, that can effectively cure asthma. CONCLUSION: Plants used in traditional Ayurvedic medicine have been utilized for millennia, advocating phyto-therapy as a treatment for a variety of illnesses. A theoretical foundation for the use of cutting-edge asthma treatments has been built with the growth of experimental research on traditional phytochemicals. In-depth phytochemical research for the treatment of asthma using Indian Traditional Ayurvedic herbs is compiled in the study. The approach for preventative therapeutics and cutting-edge alternatives to battle the molecular pathways in the pathophysiology of asthma are the key themes of the study. The phytochemical mechanism of action of traditional Ayurvedic herbs is explained to get the attention of the pharmaceutical industry so they can make future anti-asthma drugs for personalized asthma care in the community. The study develops strategies for customized phyto-therapeutics, concentrating on low-cost, side-effect-free approaches that employ bioactive phytochemicals from plants as the major source of effective anti-asthmatic therapy.

To Prescribe or Not to Prescribe?: Barriers and Motivators for Progressing Along Each Stage of the Buprenorphine Training and Prescribing Path.

This study aimed to identify the strongest barriers and motivators associated with each step toward buprenorphine prescribing (1. obtaining a waiver, 2. beginning to prescribe, and 3. prescribing to more people) among a sample of Missouri-based medical professionals (N = 130). Item weights (number of endorsements times mean rank of the item's importance) were calculated based on their responses. Across groups, lack of access to psychosocial support services, need for higher levels of care, and clinical complexity were strong barriers. Among non-prescribers (n = 57, 46.3%), administrative burden, potential of becoming an addiction clinic, and concern about misuse and diversion were most heavily weighted. Among prescribers (n = 66, 53.7%), patients' inability to afford medications was a barrier across phases. Prominent motivators among all groups were the effectiveness of buprenorphine, improvement in other health outcomes, and a personal interest in treating addiction. Only prescribers reported the presence of institutional support and mentors as significant motivators.

Inonotus obliquus aqueous extract prevents histopathological alterations in liver induced by environmental toxicant Microcystin.

Environmental toxicants like microcystins are known to adversely impact liver physiology and lead to the increased risk for abnormal liver function and even liver carcinoma. Chaga mushroom (Inonotus obliquus) is reported for various properties mainly antibacterial, antiallergic, anti-inflammatory, antioxidant, and anticancer properties. This study was aimed to assess the effect microcystin (MC-LR) on histopathology of liver in mice and a preventive measure by using aqueous extract of Inonotus obliquus (IOAE). Adult Balb/c mice were administered with MC-LR at 20 â€‹µg/kg body weight, per day, intraperitoneal (i.p.) for 4 weeks. IOAE was treated to one group of MC-LR mice at 200 â€‹mg/kg body weight, per oral, for 4 weeks. Histological staining for liver structural details and biochemical assays for functions were assessed. The results of the study showed that MC-LR drastically reduced the body weight of mice which were restored close to the range of control by IOAE treatment. MC-LR exposed mice showed 1.9, 1.7 and 2.2-fold increase in the levels of SGOT, SGPT and LDH which were restored by IOAE treatment as compared to control (one-fold). MC-LR exposed mice showed reduced level of GSH (19.83 â€‹± â€‹3.3 â€‹µM) which were regained by IOAE treatment (50.83 â€‹± â€‹3.0 â€‹µM). Similar observations were noted for catalase activity. Histological examinations show that MC-LR exposed degenerative changes in the liver sections which were restored by IOAE supplementation. The immunofluorescence analysis of caspase-3 counterstained with DAPI showed that MC-LR led to the increased expression of caspase-3 which were comparatively reduced by IOAE treatment. The cell viability decreased on increasing the concentration of MC-LR with 5% cell viability at concentration of 10 â€‹µg MC-LR/mL as that of control 100% Cell viability. The IC50 was calculated to be 3.6 â€‹µg/ml, indicating that MC-LR is chronic toxic to AML12 mouse hepatocytes. The molecular docking interaction of NF-κB-NIK with ergosterol peroxidase showed binding interaction between the two and showed the plausible molecular basis for the effects of IOAE in MC-LR induced liver injury. Collectively, this study revealed the deleterious effects of MC-LR on liver through generation of oxidative stress and activation of caspase-3, which were prevented by treatment with IOAE.

Cardiovascular risk in newly diagnosed type 2 diabetes patients in India.

BACKGROUND: Type 2 diabetes mellitus (T2DM) worldwide continues to increase, in particular in India. Early T2DM diagnosis followed by appropriate management will result in more cardiovascular event free life years. However, knowledge of the cardiovascular profile of newly diagnosed T2DM patients is still limited. The aim of this study was to understand the extent of cardiovascular disease (CVD) risk of newly diagnosed T2DM patients in India. METHODS: A cross sectional observational study was conducted to evaluate clinical laboratory and socio-demographic parameters of 5,080 newly diagnosed T2DM patients (48.3 ± 12.8 years of age; 36.7% female). In addition, we determined their cardiovascular risk according to the guidelines of the Lipid Association of India (LAI) and the criteria of the QRISK3 score. RESULTS: Of the newly T2DM diagnosed patients in India 2,007(39.5%) were classified as "High risk" and 3,073 (60.5%) were classified as "Very high risk" based on LAI criteria. On average, patients had 1.7 ± 0.9 major atherosclerotic cardiovascular disease (ASCVD) risk factors. Low HDL-C value was the most frequent major risk (2,823; 55.6%) followed by high age (2,502; 49.3%), hypertension (2,141; 42.1%), smoking/tobacco use (1,078; 21.2%) and chronic kidney disease stage 3b or higher (568; 11.2%). In addition, 4,192 (82.5%) patients appeared to have at least one cholesterol abnormality and, if the latest LAI recommendations are applied, 96.5% (4,902) presented with lipid values above recommended targets. Based on the QRISK3 calculation Indian diabetes patients had an average CVD risk of 15.3 ± 12.3%, (12.2 ± 10.1 vs. 17.1 ± 13.5 [p<0.001] for females and males, respectively). CONCLUSIONS: Newly diagnosed Indian T2DM patients are at high ASCVD risk. Our data therefore support the notion that further extension of nationwide ASCVD risk identification programs and prevention strategies to reduce the occurrence of cardiovascular diseases are warranted.

In vitro and in vivo evaluation of the anticarcinogenic and cancer chemopreventive potential of a flavonoid-rich fraction from a traditional Indian herb Selaginella bryopteris.

Prevention of cancer through nutritional intervention has gained significant recognition in recent years. Evidence revealed from mechanistic investigations coupled with molecular epidemiology show an inverse association of dietary flavonoids intake with cancer risk. The chemopreventive and anticarcinogenic potential of Selaginella bryopteris, a traditional Indian herb referred to as 'Sanjeevani' in the Ayurvedic system of medicine, was examined in the present study. Comprehensive in vitro and in vivo studies were conducted on the flavonoid-rich benzene fraction of the aqueous extract that demonstrated a significant cytoprotective activity. Biomarkers of chemoprevention such as proliferative index and status of cell-cycle regulatory proteins, antioxidant property, anti-inflammatory effect, reversal of stress-induced senescence and genoprotective effect were investigated in human and murine cell cultures. Chemopreventive potential was assessed in benzopyrene-induced lung carcinogenesis and 7,12-dimethyl benz(a)anthracene-mediated skin papillomagenesis test models. Inhibition of DNA fragmentation, unperturbed cell-cycle regulation, maintenance of intracellular antioxidant defence, anti-inflammatory activity, prevention of stress-induced senescence and genoprotective effects against methyl isocyanate carcinogenicity was observed. Medium-term anticarcinogenicity and two-stage skin papillomagenesis tests strongly substantiated our in vitro observations. Results from the present study provide evidence of anticarcinogenic and chemopreventive activities of S. bryopteris hitherto unreported and reaffirm the nutritional significance of flavonoids in cancer prevention.

Bhopal Gas Tragedy: review of clinical and experimental findings after 25 years.

The Bhopal gas tragedy is undoubtedly one of the worst industrial disasters in the history of mankind resulting in mortality of 2500-6000 and debilitating over 200 000 people. Inhabitants in the township were exposed to different degrees and there are more than 500 000 registered victims that survived the tragedy. Clinical studies have shown chronic illnesses such as pulmonary fibrosis, bronchial asthma, chronic obstructive pulmonary disease (COPD), emphysema, recurrent chest infections, keratopathy and corneal opacities in exposed cohorts. Survivors continue to experience higher incidence of reported health problems including febrile illnesses, respiratory, neurologic, psychiatric and ophthalmic symptoms. In-utero exposure to methyl isocyanate in the first trimester of pregnancy caused a persistent immune system hyper-responsiveness, which was in an evident way genetically linked with the organic exposure. Recent experimental studies have provided mechanistic understanding of methyl isocyanate exposure at a molecular level. Immunotoxic implications, toxico-genomic effect, inflammatory response, elicitation of mitochondrial oxidative stress, chromosomal and microsatellite instability have been studied comprehensively in cultured mammalian cells. Besides providing a framework for understanding potential mechanisms of toxicity of a host of other exposures, these studies may also uncover unique abnormalities thereby stimulating efforts to design newer and effective diagnostic and therapeutic strategies. The authors recommend long-term monitoring of the affected area and use of appropriate methods of investigation that include well-designed cohort studies, case-control studies for rare condition, characterization of personal exposure and accident analysis to determine the possible elements of the gas cloud.

Isocyanates induces DNA damage, apoptosis, oxidative stress, and inflammation in cultured human lymphocytes.

Isocyanates, a group of low molecular weight aromatic and aliphatic compounds containing the isocyanate group (-NCO), are important raw materials with diverse industrial applications; however, pathophysiological implications resulting from occupational and accidental exposures of these compounds are hitherto unknown. Although preliminary evidence available in the literature suggests that isocyanates and their derivatives may have deleterious health effects including immunotoxicity, but molecular mechanisms underlying such an effect have never been addressed. The present study was carried out to assess the immunotoxic response of methyl isocyanate (MIC) on cultured human lymphocytes isolated from healthy human volunteers. Studies were conducted to evaluate both dose-dependent and time-course response (n = 3), using N-succinimidyl N-methylcarbamate, a surrogate chemical substitute to MIC. Evaluation of DNA damage by ataxia telangiectasia mutated (ATM) and gamma H2AX protein phosphorylation states; measure of apoptotic index through annexin-V/PI assay, apoptotic DNA ladder assay, and mitochondrial depolarization; induction of oxidative stress by CM-H2DCFDA and formation of 8-hydroxy-2' deoxy guanosine; levels of antioxidant defense system enzyme glutathione reductase; and multiplex cytometric bead array analysis to quantify the secreted levels of inflammatory cytokines, interleukin-8, interleukin-1beta, interleukin-6, interleukin-10, tumor necrosis factor, and interleukin-12p70 parameters were carried out. The results of the study showed a dose- and time-dependent response, providing evidence to hitherto unknown molecular mechanisms of immunotoxic consequences of isocyanate exposure at a genomic level. We anticipate these data along with other studies reported in the literature would help to design better approaches in risk assessment of occupational and accidental exposure to isocyanates.

ADH1B, ALDH2, GSTM1 and GSTT1 Gene Polymorphic Frequencies among Alcoholics and Controls in the Arcadian Population of Central India

Background: Epidemiological research has highlighted the global burden of primary liver cancer cases due to alcohol consumption, even in a low consumption country like India. Alcohol detoxification is governed by ADH1B, ALDH2, GSTM1 and GSTT1 genes that encode functional enzymes which are coordinated with each other to remove highly toxic metabolites i.e. acetaldehyde as well as reactive oxygen species generated through detoxification processes. Some communities in the population appears to be at greater risk for development of the liver cancer due to genetic predispositions. Methods: The aim of this study was to screen the arcadian population of central India in order to investigate and compare the genotype distribution and allele frequencies of alcohol metabolizing genes (ADH1B, ALDH2, GSTM1 and GSTT1) in both alcoholic (N=121) and control (N=145) healthy subjects. The gene polymorphism analysis was conducted using PCR and RFLP methods. Results: The allele frequency of ALDH2 *1 was 0.79 and of ALDH2*2 was 0.21 (OR:1.12; CI (95%): 0.74-1.71). The null allele frequency for GSTM1 was 0.28 (OR:0.85; CI (95%): 0.50-1.46) and for GSTT1 was 0.20 (OR:1.93; CI (95%): 1.05-3.55). No gene polymorphism for ADH1B was not observed. The total prevalence of polymorphisms was 3.38% for ALDH2, GSTM1 and GSTT1. Conclusion: The results of this study suggested that individuals of the Central India population under study are at risk for liver disorders due to ALDH2, GSTM1 and GSTT1 gene polymorphisms. This results may have significance for prevention of alcohol dependence, alcoholic liver disorders and the likelihood of liver cancer.

Biotechnological improvement of nutritional and therapeutic value of cultivated potato.

Genetic engineering is recognized as a powerful tool for altering the genetic characteristic of crop plants. Genetic engineering has tremendous potential in developing improved potato varieties with desired agronomic traits and has been utilized for improvement of several crop plants including potato to enhance essential amino acid, protein and lipids/carbohydrates contents as well to improve stress tolerance. The pathway engineering of amino acid revealed dramatic changes in essential amino acid content and protein quality. Similarly, the vitamin pathway engineering of potato has been proved to enhance the vitamin content with increased cellular antioxidant activities. Secondary metabolites such as flavonoids have also been altered through the genetic engineering of potato. This review provides detailed reports on the advances made in genetic transformation of potato for enrichment in its nutritional and therapeutic value by an increase in functional secondary metabolites, carbohydrate, essential amino acids, proteins, lipids, vitamins and edible vaccines.

Cell-Free Circulating Epigenomic Signatures: Non-Invasive Biomarker for Cardiovascular and Other Age-Related Chronic Diseases.

The burden of cardio-vascular and other age-related non-communicable diseases are rapidly increasing worldwide. Majority of these chronic ailments are curable, if diagnosed at early stages. Candidate biomarkers of early detection are therefore essential for identification of high-risk individuals, prompt and accurate disease diagnosis, and to monitor therapeutic response. The functional significance of circulating nucleic acids that recapitulate specific disease profiles is now well established. But subtle changes in DNA sequence may not solely reflect the differentiation of gene expression patterns observed in diverse set of diseases as epigenetic phenomena play a larger role in aetiology and patho-physiology. Unlike genetic markers, knowledge about the diagnostic utility of circulating epigenetic signatures: methylated DNA; micro RNA and modified histones are deficient. Characterization of these novel entities through omics-based molecular technologies might prompt development of a range of laboratory-based strategies, thereby accelerating their broader translational purpose for early disease diagnosis, monitoring therapeutic response and drug resistance. However, largest opportunity for innovation lies in developing point-of-care tests with accurate diagnostic and higher prognostic score that is applicable for screening of high-risk populations.