Anthocyanin-rich fraction from black rice, Oryza sativa L. var. indica "Luem Pua," bran extract attenuates kidney injury induced by high-fat diet involving oxidative stress and apoptosis in obese rats.

Obesity is acknowledged as being a world health problem and increases the risk of several chronic diseases including chronic kidney disease. High-fat diet consumption and obesity-related renal disease show a close correlation with increased oxidative stress. Black rice bran extract, (BRE) Oryza sativa L. variety "Luem Pua" contains a high anthocyanin content. This study evaluated the effects of an anthocyanin-rich fraction from BRE on renal function and oxidative stress in obese rats. Male Wistar rats were fed a normal diet (ND) or high-fat diet (HF) for 16 weeks. After this, the rats were given either vehicle (HF), BRE 100 (HF100) or BRE 200 mg/kg/day (HF200) orally for 8 weeks. The HF rats had increased body weight, visceral fat weight, plasma glucose, cholesterol and triglycerides. These parameters were normalized following HF100 administration and showed a decreasing trend with HF200. Serum creatinine and renal cortical MDA were increased in the HF group but these effects were attenuated by BRE. Negative kidney injury and histopathology changes were observed following a HF, but treatment with BRE reversed these deleterious effects. These results suggest that BRE could be used as a food supplement to improve metabolic disturbance and prevent kidney dysfunction in cases of obesity.

Laparoscopic repair of vesicovaginal fistula caused by radiation therapy: Use of a perirectal fat interposition graft.

INTRODUCTION: We present a case of laparoscopic repair of vesicovaginal fistula caused by radiation therapy using a perirectal fatty tissue interposition graft. CASE PRESENTATION: A 72-year-old woman was diagnosed with vesicovaginal fistula induced by radiation therapy. Repair of the vesicovaginal fistula was achieved via laparoscopic approach. The fistula was exposed, followed by excision of fistula tract, fine dissection to achieve a traction-free approximation of bladder mucosa, then water-tight closure. An interposition graft derived from the perirectal fat was inserted to reduce the risk of repair failure. The patient did not have the incontinence problem at 1-year follow-up. CONCLUSION: The laparoscopic approach for vesicovaginal fistula repair is minimally invasiveness. Preparation of the interposition graft derived from the perirectal fatty tissue was easy and its mobility to achieve closure of the fistula was acceptable. Thus, this procedure is feasible for the repair of poorly vascularized tissues such as radiation-induced fistulas.

Agomelatine protects against obesity-induced renal injury by inhibiting endoplasmic reticulum stress/apoptosis pathway in rats.

Obesity is recognized as a risk for the development of chronic kidney disease. Excessive fat accumulation in obesity is associated with the overproduction of reactive oxygen species with the underproduction of antioxidant mechanisms generating oxidative stress together with chronic low-grade inflammation which subsequently leads to the development of several obesity-related complications. It has been suggested that the abnormal lipid accumulation can induce endoplasmic reticulum (ER) stress and cellular apoptosis in several tissue types. Agomelatine is a relatively new antidepressant which is a synthetic agonist of melatonin. Previous study reported the antioxidant and anti-inflammatory effects of agomelatine. In this study, we investigated the therapeutic effects of agomelatine in obesity-related renal injury. Male Wistar rats were fed with normal diet or high-fat diet (HF) for 16 weeks. After that, vehicle or agomelatine or vildagliptin was orally administered to HF rats for 4 weeks. Our results indicated that HF rats demonstrated insulin resistance which was accompanied by an impairment of renal function and renal organic anion transporter 3 (Oat3) function as well as renal oxidative stress, ER stress, and apoptosis. Interestingly, agomelatine treatment not only improved the metabolic parameters, renal function and renal Oat3 function but also attenuated renal oxidative stress, ER stress and subsequent apoptosis. Therefore, agomelatine exerted renoprotective effects in obese insulin-resistant condition. These results suggested that agomelatine could be used as a drug to improve metabolic disturbance and prevent kidney dysfunction in obese condition.

Dapagliflozin ameliorates pancreatic injury and activates kidney autophagy by modulating the AMPK/mTOR signaling pathway in obese rats.

Chronic consumption of a high-fat diet induces obesity and impairs the ultra-structure of organs and tissues. We examined the effect of sodium-glucose cotransporter 2 (SGLT2) inhibitor-dapagliflozin on renal and pancreatic injuries in obese condition. Rats were fed a high-fat diet for 16 weeks to induce obesity. After that, dapagliflozin or vildagliptin, 1.0 or 3.0 mg/kg/day, respectively, was administered by oral gavage for 4 weeks. The effects of dapagliflozin on insulin resistance, kidney autophagy, pancreatic oxidative stress, endoplasmic reticulum (ER) stress, inflammation, and apoptosis in high-fat diet-induced obese rats were elucidated. High-fat-diet fed rats demonstrated metabolic abnormalities including increased body weight, visceral fat weight, plasma insulin, plasma cholesterol, homeostasis model assessment (HOMA) index, and TAUCg, indicating the obese-insulin resistant and glucose intolerance conditions. Also, high-fat-diet fed rats exhibited significant pancreatic injury accompanied by decreased kidney autophagy. Dapagliflozin or vildagliptin treatment for 4 weeks ameliorated pancreatic oxidative stress, ER stress, inflammation, and apoptosis and restored kidney autophagy in obese rats. Moreover, the morphology changes of the pancreas and kidney were improved in the treated groups. Interestingly, dapagliflozin showed higher efficacy than vildagliptin in improving body weight, visceral fat weight, plasma cholesterol level, and pancreatic oxidative stress in our model. Taken together, the present study demonstrated that the therapeutic effects of dapagliflozin attenuated pancreatic injury, pancreatic oxidative stress, ER stress, inflammation, apoptosis, and exerted renoprotective effects by restoring autophagic signaling in obese rats.

Atorvastatin attenuates obese-induced kidney injury and impaired renal organic anion transporter 3 function through inhibition of oxidative stress and inflammation.

An excessive consumption of high-fat diet can lead to the alterations of glucose and lipid metabolism, impaired insulin signaling and increased ectopic lipid accumulation resulting in renal lipotoxicity and subsequent renal dysfunction. Atorvastatin is a lipid-lowering drug in clinical treatment. Several studies have reported that atorvastatin has several significant pleiotropic effects including anti-inflammatory, antioxidant, and anti-apoptotic effects. However, the effects of atorvastatin on metabolic disturbance and renal lipotoxicity in obesity are not fully understood. In this study, obesity in rat was developed by high-fat diet (HFD) feeding for 16 weeks. After that, the HFD-fed rats were received either a vehicle (HF), atorvastatin (HFA) or vildagliptin (HFVIL), by oral gavage for 4 weeks. We found that HF rats showed insulin resistance, visceral fat expansion and renal lipid accumulation. Impaired renal function and renal organic anion transporter 3 (Oat3) function and expression were also observed in HF rats. The marked increases in MDA level, renal injury and NF-κB, TGF-ß, NOX-4, PKC-α expression were demonstrated in HF rats. Atorvastatin or vildagliptin treatment attenuated insulin resistance and renal lipid accumulation-induced lipotoxicity in HFA and HFVIL rats. Moreover, the proteins involved in renal inflammation, fibrosis, oxidative stress and apoptosis were attenuated leading to improved renal Oat3 function and renal function in the treated groups. Interestingly, atorvastatin showed higher efficacy than vildagliptin in improving insulin resistance, renal lipid accumulation and in exerting renoprotective effects in obesity-induced renal injury and impaired renal Oat3 function.

Dapagliflozin attenuates renal gluconeogenic enzyme expression in obese rats.

The kidneys release glucose into the systemic circulation through glucose reabsorption and renal gluconeogenesis. Currently, the significance of renal glucose release in pathological conditions has become a subject of interest. We examined the effect of sodium-dependent glucose cotransporter 2 inhibitor (SGLT2i) on renal gluconeogenic enzyme expression in obese rats. Male Wistar rats (180-200 g) were fed either a normal diet (ND, n = 6) or a high-fat diet. At 16 weeks, after confirming the degree of glucose intolerance, high-fat diet-fed rats were randomly subdivided into three groups (n = 6/group): untreated group (HF), treated with dapagliflozin 1 mg/kg/day (HFSG) and treated with metformin 30 mg/kg/day (HFM). The treatment was continued for 4 weeks. We observed that dapagliflozin or metformin mitigated the enhanced expression of renal gluconeogenic enzymes, PEPCK, G6Pase and FBPase, as well as improved glucose tolerance and renal function in obese rats. Dapagliflozin downregulated the elevated expression of gluconeogenic transcription factors p-GSK3ß, p-CREB and coactivator PGC1α in the renal cortical tissue. Metformin reduced the expression levels of renal cortical FOXO1 and CREB. Furthermore, reduced renal insulin signaling was improved and renal oxidative stress was attenuated by either dapagliflozin or metformin treatment in obese rats. We concluded that glucose tolerance was improved by dapagliflozin in obese prediabetic rats by suppressing renal glucose release from not only glucose reabsorption but also renal gluconeogenesis through improving renal cortical insulin signaling and oxidative stress. The efficacy of dapagliflozin in improving renal insulin signaling, oxidative stress and renal function was greater than that of metformin.

Dapagliflozin not only improves hepatic injury and pancreatic endoplasmic reticulum stress, but also induces hepatic gluconeogenic enzymes expression in obese rats.

BACKGROUND: With an increasing prevalence of obesity and metabolic syndrome, exploring the effects and delineating the mechanisms of possible therapeutic agents are of critical importance. We examined the effects of SGLT2 inhibitor-dapagliflozin on insulin resistance, hepatic gluconeogenesis, hepatic injury and pancreatic ER stress in high-fat diet-induced obese rats. MATERIALS AND METHODS: Male Wistar rats were fed with normal diet (ND) or high-fat diet for 16 weeks. Then high-fat rats were given vehicle (HF) or dapagliflozin (1 mg/kg/day; HFDapa) or metformin (30 mg/kg/day; HFMet) for another 4 weeks. RESULTS: We found that dapagliflozin ameliorated high-fat diet-induced insulin resistance. The fasting plasma glucose level was comparable among groups, although dapagliflozin treatment led to substantial glycosuria. Hepatic gluconeogenic enzymes, PEPCK, G6Pase and FBPase, expression was not different in HF rats compared with ND rats. Meanwhile, dapagliflozin-treated group exhibited the elevation of these enzymes in parallel with the rise of transcription factor CREB, co-factor PGC1α and upstream regulator SIRT1. Hepatic oxidative stress, inflammation and NAFLD activity score as well as hepatic and pancreatic ER stress and apoptosis in obese rats were attenuated by dapagliflozin. CONCLUSION: We conclude that dapagliflozin improved obesity-related insulin resistance, hepatic and pancreatic injury independent of fasting plasma glucose level. Of note, dapagliflozin-induced glycosuria apparently triggered the up-regulation of hepatic gluconeogenic enzymes to prevent hypoglycemia.

Molecular signaling mechanisms of renal gluconeogenesis in nondiabetic and diabetic conditions.

The kidneys are as involved as the liver in gluconeogenesis which can significantly contribute to hyperglycemia in the diabetic condition. Substantial evidence has demonstrated the overexpression of rate-limiting gluconeogenic enzymes, especially phosphoenolpyruvate carboxykinase and glucose 6 phosphatase, and the accelerated glucose release both in the isolated proximal tubular cells and in the kidneys of diabetic animal models and diabetic patients. The aim of this review is to provide an insight into the mechanisms that accelerate renal gluconeogenesis in the diabetic conditions and the therapeutic approaches that could affect this process in the kidney. Increase in gluconeogenic substrates, reduced insulin concentration or insulin resistance, downregulation of insulin receptors and insulin signaling, oxidative stress, and inappropriate activation of the renin-angiotensin system are likely to participate in enhancing renal gluconeogenesis in the diabetic milieu. Several studies have suggested that controlling glucose metabolism at the renal level favors effective overall glycemic control in both type 1 and type 2 diabetes. Therefore, renal gluconeogenesis may be a promising target for effective glycemic control as a therapeutic strategy in diabetes.

Late Middle Eocene primate from Myanmar and the initial anthropoid colonization of Africa.

Reconstructing the origin and early evolutionary history of anthropoid primates (monkeys, apes, and humans) is a current focus of paleoprimatology. Although earlier hypotheses frequently supported an African origin for anthropoids, recent discoveries of older and phylogenetically more basal fossils in China and Myanmar indicate that the group originated in Asia. Given the Oligocene-Recent history of African anthropoids, the colonization of Africa by early anthropoids hailing from Asia was a decisive event in primate evolution. However, the fossil record has so far failed to constrain the nature and timing of this pivotal event. Here we describe a fossil primate from the late middle Eocene Pondaung Formation of Myanmar, Afrasia djijidae gen. et sp. nov., that is remarkably similar to, yet dentally more primitive than, the roughly contemporaneous North African anthropoid Afrotarsius. Phylogenetic analysis suggests that Afrasia and Afrotarsius are sister taxa within a basal anthropoid clade designated as the infraorder Eosimiiformes. Current knowledge of eosimiiform relationships and their distribution through space and time suggests that members of this clade dispersed from Asia to Africa sometime during the middle Eocene, shortly before their first appearance in the African fossil record. Crown anthropoids and their nearest fossil relatives do not appear to be specially related to Afrotarsius, suggesting one or more additional episodes of dispersal from Asia to Africa. Hystricognathous rodents, anthracotheres, and possibly other Asian mammal groups seem to have colonized Africa at roughly the same time or shortly after anthropoids gained their first toehold there.

Talar morphology, phylogenetic affinities, and locomotor adaptation of a large-bodied amphipithecid primate from the late middle eocene of Myanmar.

A well-preserved fossil talus [National Museum of Myanmar Primates (NMMP) 82] of a large-bodied primate is described from the late middle Eocene Pondaung Formation of central Myanmar. The specimen was collected at Thandaung Kyitchaung, a well-known amphipithecid primate-bearing locality near the village of Mogaung. NMMP 82 adds to a meager but growing sample of postcranial remains documenting the large-bodied primates of the Pondaung Formation. This new talus exhibits a suite of features that resemble conditions found in living and fossil haplorhine primates, notably anthropoids. As such, the phylogenetic signal deriving from the morphology of NMMP 82 conflicts with that provided by NMMP 20, a partial skeleton (including a fragmentary calcaneus) of a second large-bodied Pondaung primate showing undoubted adapiform affinities. Analysis subtalar joint compatibility in a hypothetical NMMP 82/NMMP 20 combination (talus/calcaneus) reveals a substantial degree of functional mismatch between these two tarsal bones. The functional incongruence in subtalar joint morphology between NMMP 20 and NMMP 82 is consistent with the seemingly divergent phylogenetic affinities of these specimens, indicating that two higher level taxa of relatively large-bodied primates are documented in the Pondaung Formation. On the basis of its size and morphology, we refer the NMMP 82 talus to the large-bodied amphipithecid Pondaungia. The occurrence of anthropoid-like tali in the Pondaung Formation obviates the need to invoke homoplasy to explain the shared, derived dental characters that are common to amphipithecids and undoubted anthropoids. Functionally, the NMMP 82 talus appears to have pertained to a primate that is engaged in active quadrupedalism in an arboreal environment along broad and subhorizontal branches. The primate taxon represented by NMMP 82 was capable of climbing and leaping, although it was not particularly specialized for either of these activities.