Directing group assisted para-selective C-H alkynylation of unbiased arenes enabled by rhodium catalysis.

Regioselective C-H alkynylation of arenes via C-H activation is challenging yet a highly desirable transformation. In this regard, directing group assisted C(sp2)-H alkynylation of arenes offers a unique opportunity to ensure precise regioselectivity. While the existing methods are mainly centered around ortho-C-H alkynylation and a few for meta-C-H alkynylation, the DG-assisted para-selective C-H alkynylation is yet to be reported. Herein we disclose the first report on Rh-catalyzed para-C-H alkynylation of sterically and electronically unbiased arenes. The para-selectivity is achieved with the assistance of a cyano-based directing template and the selectivity remained unaltered irrespective of the steric and electronic influence of the substituents. The post-synthetic modification of synthesized para-alkynylated arenes is also demonstrated. The mechanistic intricacies of the developed protocol are elucidated through experimental and computational studies.

Health risk assessment of arsenic, lead and cadmium from milk consumption in Punjab, India.

Milk is an integral part of the human diet and its contamination with heavy metals may alter the health of its consumers. The study was conducted to assess the health risk associated with the heavy metals in milk samples collected from urban and rural households of Ludhiana and Bathinda districts of Punjab, India. One hundred and fifty milk samples were analyzed for heavy metals i.e. arsenic, cadmium, lead and mercury using Inductively Coupled Plasma Mass Spectrometry ICP-MS. The health risks, such as non-carcinogenic and carcinogenic risks from heavy metals in milk samples, were calculated for selected males and females of adults, children and elderly subjects. The results indicated that the arsenic, cadmium and lead content in milk samples were within permissible limit whereas mercury was not detected in any sample. The mean values showed that the selected urban and rural population of both districts was safe from non-carcinogenic risk associated with heavy metal content of milk. However, urban (50% males and 86% females) and rural (25% males) children of Bathinda district were at risk of cancer from arsenic and cadmium present in milk samples, respectively. It was also observed that the selected population of both districts were safe from carcinogenic risk due to the combined effects of heavy metals. It was concluded that even with a small amount of heavy metal in milk samples, the rural adults, rural male children and urban female children of Bathinda district had carcinogenic risk due to milk consumption. Hence, regular monitoring and testing of milk samples must be done as a public health measure to prevent heavy metal contamination in milk to safeguard the health of consumers.

Modified cereal bran (MCB) from finger millet, kodo millet, and rice bran prevents high-fat diet-induced metabolic derangements.

Cereal bran consumption improves gastrointestinal and metabolic health. Unprocessed cereal brans have a limited shelf-life and contain anti-nutrient phytochemicals. In the present study, lipids and antinutrients (flavonoids, tannin, and polyphenol) were removed from finger millet, kodo millet and rice bran using chemo-enzymatic processing. The thus-obtained modified cereal brans (MCBs) were evaluated for their potential in preventing high fat diet (HFD)-induced obesity. C57BL/6 mice were fed a HFD or a HFD supplemented with 10% w/w modified finger millet bran (mFMB), modified kodo millet bran (mKMB), modified rice bran (mRB), or a combination of the modified brans (1 : 1 : 1) for twelve weeks. The MCBs reduced HFD-induced body weight gain, improved glucose homeostasis, decreased the Firmicutes/Bacteroidetes ratio, and increased the short chain fatty acid (SCFA) levels in the cecum. Liver dyslipidemia, oxidative stress, inflammation, visceral white adipose tissue (vWAT) hypertrophy, and lipolysis were also prevented by the MCBs. Among the individual MCBs, mRB showed a greater effect in preventing HFD-induced increase in the inflammatory cytokines (IL-6, TNF-α, and LPS) than mFMB and mKMB. mFMB and mKMB supplementation more significantly restored the relative abundance of Akkermansia muciniphila and butyrate-producing genera such as Lachnospiraceae, Eubacterium, and Ruminococcus than mRB. Ex vivo gut permeability assay, immunohistochemistry of tight junction proteins, and gene expression analysis in the colon revealed that the combination of three brans was better in preventing HFD-induced leaky gut in comparison to the individual brans. Hierarchical clustering analysis showed that the combination group was clustered closest to the NPD group, suggesting an additive effect. Our study implies that a combination of mFMB, mKMB, and mRB could be used as a nutraceutical or functional food ingredient for preventing HFD-induced gut derangements and associated metabolic complications.

A synbiotic combination of Bifidobacterium longum Bif10 and Bifidobacterium breve Bif11, isomaltooligosaccharides and finger millet arabinoxylan prevents dextran sodium sulphate induced ulcerative colitis in mice.

Decreased bifidobacterial abundance, disrupted gut barrier function, dysregulated immune response and ulceration have been reported in the gut microbiota of IBD patients. Non-digestible carbohydrates with bifidogenic effect enrich the gut microbiota with Bifidobacterium spp. and could help in overcoming inflammatory gut conditions. In this study, the protective effect of Bifidobacterium longum Bif10 and Bifidobacterium breve Bif11; isomaltooligosaccharides (IMOS); Finger millet arabinoxylan (FM-AX) and their Synbiotic mix were evaluated against dextran sodium sulphate (DSS) induced UC in male Balb/c mice for 25 days. All the interventions ameliorated symptoms of colitis such as disease activity index (DAI), histological damage to the colon, gut-bacterial dysbiosis and inflammation. However, the synbiotic mix was more potent in amelioration of some of the parameters such as decreased TNF-α and lipocalin levels; increased anti-inflammatory markers (IL-10 and IL-22), and improved short chain fatty acids (SCFAs) levels in the cecum content. Furthermore, mouse colitis histological scoring (MCHI) also suggested the preventive role of synbiotic mix. All the dietary interventions aid in improving the DAI and immune parameters; restoration or regeneration of the altered selected gut bacteria, enhances the SCFA production, strengthens gut barrier, prevents gut inflammation and decreases the colonic MCHI score in DSS fed mice.

Intrarectal Capsazepine Administration Modulates Colonic Mucosal Health in Mice.

Antagonism of transient receptor potential vanniloid-1 (TRPV1) and desensitization of transient receptor potential ankyrin-1 (TRPA1) nociceptors alleviate inflammatory bowel diseases (IBD)-associated chronic pain. However, there is limited literature available about their role in regulating the mucosal layer, its interaction with host physiology, and luminal microbial community. The present study focuses on the effects' intra rectal administration of capsazepine (modulator of TRPA1/TRPV1 expressing peptidergic sensory neurons) on colonic mucus production and gut health. We performed histological analysis, gut permeability alteration, gene expression changes, metabolite profiling, and gut microbial abundance in the ileum, colon, and cecum content of these animals. Intra rectal administration of capsazepine modulates TRPA1/TRPV1-positive nociceptors (behavioral pain assays) and resulted in damaged mucosal lining, increased gut permeability, and altered transcriptional profile of genes for goblet cell markers, mucus regulation, immune response, and tight junction proteins. The damage to mucosal lining prevented its role in enterosyne (short chain fatty acids) actions. These results suggest that caution must be exercised before employing TRPA1/TRPV1 modulation as a therapeutic option to alleviate pain caused due to IBD.

Whole genome re-sequencing of indian wheat genotypes for identification of genomic variants for grain iron and zinc content.

BACKGROUND: Whole-genome sequencing information which is of abundant significance for genetic evolution, and breeding of crops. Wheat (Triticum spp) is most widely grown and consumed crops globally. Micronutrients are very essential for healthy development of human being and their sufficient consumption in diet is essential for various metabolic functions. Biofortification of wheat grains with iron (Fe) and zinc (Zn) has proved the most reliable and effective way to combat micronutrient associated deficiency. Genetic variability for grain micronutrient could provide insight to dissect the traits. METHODS AND RESULTS: In the current study, 1300 wheat lines were screened for grain Fe and Zn content, out of which only five important Indian wheat genotypes were selected on the basis of Fe and Zn contents. These lines were multiplied during at the National Agri-Food Biotechnology Institute (NABI) and re-sequenced to identify genomic variants in candidate genes for Fe and Zn between the genotypes. Whole genome sequencing generated Ì´ 12 Gb clean data. Comparative genome analysis identified 254 genomic variants in the candidate genes associated with deleterious effect on protein function. CONCLUSIONS: The present study demonstrated the fundamental in understanding the genomic variations for Fe and Zn enrichment to generate healthier wheat grains.

Occupational lead exposure is an independent modulator of hypertension and poor pulmonary function: A cross-sectional comparative study in lead-acid battery recycling workers.

Blood lead level (BLL) is the primary biomarker for lead-exposure monitoring in occupationally exposed workers. We evaluated occupational lead-exposure (OE) impact on cardiopulmonary functions in lead-acid battery recycling unit workers. Seventy-six OE cases and 30 control subjects were enrolled for questionnaire-based socio-demographic, dietary, tobacco usage, and medical history data. Anthropometric measurements, systolic and diastolic blood pressure (SBP and DBP), and pulmonary function tests were performed. Venous blood was collected for BLL, hematological analysis, and biochemical analysis. OE caused a significant increase in BLL, SBP, DBP, and small airways obstruction in lung function tests. It also impaired platelet indices, affected renal and liver biochemical measurements, and promoted oxidative stress and DNA damage. Multilinear regression analysis suggested that BLL affected SBP (ß = 0.314, p = .034) and increased small airways obstruction (FEV1/FVC, ß = -0.37, p = .05; FEV25-75%, ß = -0.351, p = .016). Higher BLL appears to be an independent modulator of hypertension and poor pulmonary function upon occupational lead exposure in lead-acid battery recyclers.

Mucin secretory action of capsaicin prevents high fat diet-induced gut barrier dysfunction in C57BL/6 mice colon.

The gut barrier - including tight junction proteins (TJPs) and mucus layers, is the first line of defense against physical, chemical or pathogenic incursions. This barrier is compromised in various health disorders. Capsaicin, a dietary agonist of Transient receptor potential vanilloid 1 (TRPV1) channel, is reported to alleviate the complications of obesity. While it is well known to improve energy expenditure and metabolism, and prevent dysbiosis, the more local effects on the host gut - particularly the gut barrier and mucus system remain elusive. To investigate the effect of capsaicin on the gut barrier and mucus production and to understand the involvement of mucus, bacteria, and TRPV1 in these phenomena, we employed a diet-induced obesity model in C57BL/6 mice, and capsaicin (2 mg/kg/day p.o.) or mucin (1 g/kg/day p.o.) as interventions, for 12 weeks. Parameters like weight gain, glucose homeostasis, TJPs expression, mucus staining, intestinal permeability etc were studied. 16 S rDNA sequencing and in vitro Ca2+ measurement experiments were performed to explore the role of microbiota in the beneficial effects. Mucin feeding reflected several anti-obesity effects produced by capsaicin, suggesting that mucus modulation might play a crucial role in capsaicin-induced anti-obesity effects. 16 S rDNA sequencing and in vitro Ca2+ measurement experiments pointed to TRPV1 modulation by bacteria besides capsaicin. Capsaicin, bacteria and the host mucus system seem to act in a cyclic cascade involving TRPV1, which can be activated by capsaicin and various bacteria. These findings provide new insight into the role of TRPV1 in maintaining a healthy gut environment.

Short-chain fatty acids increase intracellular calcium levels and enhance gut hormone release from STC-1 cells via transient receptor potential Ankyrin1.

Short-chain fatty acids (SCFAs), metabolites of colonic bacterial fermentation of complex carbohydrates, are closely related to the release of gut hormones. In this study, we examined the involvement of transient receptor potential ankyrin 1 (TRPA1) in SCFA-induced increase in intracellular calcium ([Ca2+ ]i ) and its impact on gut hormone secretion using naturally TRPA1 expressing intestinal secretin tumour cell-1 (STC-1) cell line. Individual SCFAs and their physiological mix enhanced calcium influx in TRPA1-dependent manner. SCFA mix also significantly increased membrane expression of TRPA1. Gene expression studies revealed that SCFA mix elevated the expression of genes involved in calcium-activated calcineurin pathway in TRPA1-dependent manner and cAMP-regulated transcriptional co-activators (CRTC) pathway independent to TRPA1. Genes representing synaptic vesicular exocytosis and gut hormone precursors were significantly elevated with SCFA mix treatment. Treatment with TRPA1 antagonist HC-030031 markedly reduced these effects. The release of gut hormones was elevated with 10 mm SCFA mix in TRPA1 dependent manner. Our in vivo prebiotic study results suggested presence of an environment conducive to increase in gut hormone secretion. Overall, our findings provide an evidence for the possible role of TRPA1 in SCFA-induced increase in gut hormone secretion, hence another mechanism of action for prebiotics.