UNASSIGNED: Sodium-glucose co-transporter 2 (SGLT2) inhibitor, a new class of glucose lowering agents, has been shown to be reno-protective in diabetes.
UNASSIGNED: We aimed to explore whether SGLT2 inhibitor ipragliflozin has a direct reno-protective effect on non-diabetic chronic kidney disease (CKD) in mice.
UNASSIGNED: CKD mice was induced by feeding of 0.25% w/w adenine containing diet. Low dose ipragliflozin (0.03 or 0.1 mg/kg/day) was orally administered to CKD mice for 4 weeks, concomitantly with adenine containing diet.
UNASSIGNED: CKD mice exhibited increases in kidney weight/body weight ratio, plasma creatinine levels, urinary fatty acid binding protein 1 excretion and plasma interleukin-6 levels, and a decrease in hematocrit, accompanied by morphological changes such as crystal deposits in the tubules, tubular dilatation, interstitial fibrosis, and increased 8-hydroxy-2\'-deoxyguanosine staining. Low dose ipragliflozin (0.03 or 0.1 mg/kg/day) did not affect either plasma glucose levels or urinary glucose excretion, while it improved levels in plasma creatinine (P < 0.05 for 0.03 mg/kg/day, P < 0.001 for 0.1 mg/kg/day), interleukin-6 (P < 0.05 for 0.1 mg/kg/day) and hematocrit (P < 0.05 for 0.1 mg/kg/day), and morphological changes dose-dependently except crystal deposit formation in the CKD mice.
UNASSIGNED: Low-dose ipragliflozin has a reno-protective effect in non-diabetic adenine-induced CKD mice, independently of plasma glucose levels and urinary glucose excretion. Low dose SGLT2 inhibitor may be a useful therapeutic option for non-diabetic CKD with the advantage of fewer adverse effects.

Gas-chromatography-mass-spectrometry revealed the presence of various bioactive compounds with anticancer properties in protocorm-like-body (PLB) cultures of a Dendrobium hybrid orchid (Dendrobium Enopi x Dendrobium Pink Lady). Pre-illumination of red fluorescent light lessened the stimulating effects of light-emitting diodes (LEDs) on secondary metabolites production among in vitro PLB cultures, possibly due to habituation. The highest flavonoid content of 16.79 μmol/ g of fresh weight (FW) was achieved under blue-red (1:1) LED for PLBs pre-treated with white LED for more than 3 subculture cycles. Phenolics content significantly reduced as PLBs pre-cultured under red fluorescent light for 2 subculture cycles were exposed to LED illuminations, where far red LED resulted in the lowest total phenolic content (18.85 μmol/ g FW). High intensity green LED (16.9 μmol/s) enhanced the accumulation of phenolics while amino acids such as L-leucine, glycine and proline exhibited no significant stimulating effect for secondary metabolites production.

Fluoride intoxication generates free radicals, causing oxidative stress that plays a critical role in the progression of nephropathy. In the present study, we hypothesized that epigallocatechin gallate (EGCG), found in green tea, protects the kidneys of rats treated with fluoride by preventing oxidative stress, inflammation, and apoptosis. Pretreatment of fluoride-treated rats with EGCG resulted in a significant normalization of creatinine clearance and levels of urea, uric acid, and creatinine. Fluoride intoxication significantly increased renal oxidative stress markers and decreased the levels of renal enzymatic and non-enzymatic antioxidants. In addition, renal NO, TNF-α, IL-6 and NF-κB were also increased in the renal tissue of fluoride-treated rats. Further, EGCG pretreatment produced a significant improvement in renal antioxidant status and reduced lipid peroxidation, protein carbonylation and the levels of inflammatory markers in fluoride-treated kidney. Similarly, mRNA and protein analyses showed that EGCG pretreatment normalized the renal expression of Nrf2/Keap1 and its downstream regulatory proteins in fluoride-treated rat kidney. EGCG also effectively attenuated fluoride-induced renal apoptosis by the up-regulation of anti-apoptotic proteins such as Bcl-2 and down-regulation of Bax, caspase-3, caspase-9 and cytochrome c. Histology and immunohistochemical observations of Kim-1 provided further evidence that EGCG effectively protects the kidney from fluoride-mediated oxidative damage. These results suggest that EGCG ameliorates fluoride-induced oxidative renal injury by activation of the Nrf2/HO-1 pathway.

Corals respond to heat pulses that cause bleaching with massive transcriptional change, but the immediate responses to stress that lead up to these shifts have never been detailed. Understanding these early signals could be important for identifying the regulatory mechanisms responsible for bleaching and how these mechanisms vary between more and less resilient corals. Using RNA sequencing (RNAseq) and sampling every 30 minutes during a short-term heat shock, we found that components of the transcriptome were significantly upregulated within 90 min and after a temperature increase of +2 °C. The developmental transcription factor, Krüppel-like factor 7, was highly expressed within 60 min, and stress-related transcription factors such as Elk-3 were highly expressed starting at 240 min. The sets of genes enriched for early transcriptional response to heat stress included heat shock proteins, small GTPases, and proteasome genes. Retrovirus-related Pol polyproteins from transposons were significantly expressed throughout the whole experiment. Lastly, we propose a model for early transcriptional regulation of protein degradation and cell adhesion response that may ultimately lead to the bleaching and stress response.

Nonalcoholic fatty liver (NAFL) is an emerging global epidemic which progresses to nonalcoholic steatohepatitis (NASH) and cirrhosis in a subset of subjects. Various reviews have focused on the etiology, epidemiology, pathogenesis and treatment of NAFLD. This review highlights specifically the triggers implicated in disease progression from NAFL to NASH. The integrating role of genes, dietary factors, innate immunity, cytokines and gut microbiome have been discussed.

With advancements in immunosuppressive strategies and availability of better immunosuppressive agents, survival rate following liver transplantation has improved significantly in the recent times. Besides improvements in surgical techniques, the most important factor that has contributed to this better outcome is the progress made in the field of immunosuppression. Over the last several years, the trend has changed to tailored immunosuppression with the aim of achieving optimal graft function while avoiding its undesirable side effects. Induction agents are no longer used routinely and the aim is to provide minimal immunosuppression in the maintenance phase. The present review discusses the various types of immunosuppressive agents, their mechanism of action, clinical utility, advantages and disadvantages, and their side effects in short and long-term. It also discusses about tailoring immunosuppression in presence of various situations such as renal dysfunction, metabolic syndrome, hepatitis C recurrence, cytomegalovirus infections and so on. The issue of chronic kidney disease and the available renal sparing immunosuppressive strategies has been particularly stressed upon. Finally, it discusses about the practical aspects of various immunosuppression regimens including drug monitoring.