Sidhartha D. Ray

Hepatocellular carcinoma and microRNA: new perspectives on therapeutics and diagnostics.

Hepatocellular carcinoma (HCC) remains one of the most lethal forms of cancer in the world. In this arena, utilities of microRNA (miRNA) as a sophisticated tool, in therapeutics and diagnostics, remains a prime focus among the leading researchers. It is well known that viral hepatitis, chronic alcoholism and metabolic syndrome are the prime causes of HCCs. Nevertheless, HCCs are usually diagnosed at late stages by using current serum biomarkers. Most epidemiological studies have found the survival rate in HCC cases to be relatively low. Therefore, development of effective noninvasive biomarkers for early detention of HCC and new strategies for HCC treatment remains a high priority research area on the shoulders of liver oncologists. Accumulating evidence in cancer diagnostics and therapeutics indicates that miRNAs involve in HCC progression, which may serve as sensitive biomarkers for detecting carcinogenesis and monitoring therapies of HCC. This review focuses on the role of miRNAs in the diagnostics and therapeutics of HCC.

Anti‐diabetic and Anti‐hyperlipidemic Effects and Safety of Salacia reticulata and Related Species

Extracts of Salacia reticulata Wight (Hypocrataceae) roots, stems, and leaves have been used in Asia for hundreds of years for the folkloric treatment of diabetes and other health problems. Constituents that have been identified as exhibiting anti‐diabetic effects include salacinol, kotalanol, ponkorinol, salaprinol, and their corresponding de‐0‐sulfonated compounds. Mangiferin, kotalagenin 16‐acetate and various proanthocyanidin oligomers have also been isolated. Studies indicate that Salacia extracts modulate multiple targets that influence carbohydrate and lipid metabolism including α‐glucosidase, aldose reductase, pancreatic lipase, peroxisomal proliferator‐activated receptor‐α, glucose transporter‐4 mediated glucose uptake, and angiotensin II type 1 receptor. Furthermore, Salacia extracts exhibit free radical scavenging, antioxidant and hepatoprotectant activities. In human studies, Salacia extracts have been shown to decrease plasma glucose and insulin levels, decrease HbA1c, and modulate serum lipid levels with no adverse effects being reported. Similar results have been demonstrated in rat and mouse models as well as in vitro systems. Safety of S.u2009reticulata and other Salacia species as S.u2009oblonga and S.u2009chinensis in rats and mice indicate that extracts are exceedingly safe. No clinical studies have examined the effects of Salacia extracts on human weight loss, although weight loss and decreases in weight gain have been demonstrated in animal models. Because of the large number of pharmacologically active compounds, it is difficult to establish standards for extracts.

Protective effects of the resveratrol analog piceid in dopaminergic SH-SY5Y cells

Age-related motor deficits, such as loss of balance and coordination, are caused, in part, by loss of dopaminergic neurons. Oxidative stress is known to play a role in this neuronal loss. Resveratrol, a natural antioxidant with anticancer and anti-inflammatory potential, has been shown to protect dopaminergic-like cells (SH-SY5Y) against oxidative stress. However, the low bioavailability of resveratrol makes it worthwhile to explore newer compounds with similar properties. Piceid (RV8), an analog of resveratrol, has greater bioavailability than resveratrol, and our studies found that piceid (10, 20, 30xa0µM) protects SH-SY5Y cells against oxidative stress. Our investigations also found that the neuroprotection afforded by piceid was decreased when the MAP kinases, ERK1/2 and ERK5, were independently inhibited. Since oxidative stress is considered a master operator of apoptosis, our study also scrutinized dopamine-induced apoptosis and whether caspase-3/7 and Bcl-2 are involved, following piceid pretreatment followed by dopamine exposure. Our findings suggested that piceid pretreatment inhibited the dopamine-induced increase in caspase-3/7 activity and dopamine-induced loss of Bcl-2 expression. Overall, these findings suggest that the neuroprotective effects of piceid are mediated via the activation of ERK1/2, ERK5, and inhibition of apoptosis caused by oxidative stress.

Metals and Metal Antagonists

The Side Effects of Drugs Annuals forms a series of volumes in which the adverse effects of drugs and adverse reactions to them are surveyed. The series supplements the contents of Meylers Side Effects of Drugs: The International Encyclopedia of Adverse Drug Reactions and Interactions. This review of the January 2016–December 2016 publications on metal antagonists and selected metals includes ammonium tetrathiomolybdate, deferasirox, deferiprone, deferoxamine/desferrioxamine, deferitazole, hydroxyurea, d-penicillamine, silymarin, polystyrene sulphonates, trientine, 1-(N-acetyl-6-aminohexyl)-3-hydroxy-2-methylpyridin-4-one (CM1), and the selected metals cadmium, copper, lithium, manganese, and zinc.