Kidney podocytes represent a key constituent of the glomerular filtration barrier. Identifying the molecular mechanisms of podocyte injury and survival is important for better understanding and management of kidney diseases. KIBRA (dney in protein), an upstream regulator of the Hippo signaling pathway encoded by the gene, shares the pro-injury properties of its putative binding partner dendrin and antagonizes the pro-survival signaling of the downstream Hippo pathway effector YAP (Yes-associated protein) in and MCF10A cells. We recently identified YAP as an essential component of the glomerular filtration barrier that promotes podocyte survival by inhibiting dendrin pro-apoptotic function. Despite these recent advances, the signaling pathways that mediate podocyte injury remain poorly understood. Here we tested the hypothesis that, similar to its role in other model systems, KIBRA promotes podocyte injury. We found increased expression of KIBRA and phosphorylated YAP protein in glomeruli of patients with biopsy-proven focal segmental glomerulosclerosis (FSGS). KIBRA/ overexpression in murine podocytes promoted LATS kinase phosphorylation, leading to subsequent YAP Ser-127 phosphorylation, YAP cytoplasmic sequestration, and reduction in YAP target gene expression. Functionally, KIBRA overexpression induced significant morphological changes in podocytes, including disruption of the actin cytoskeletal architecture and reduction of focal adhesion size and number, all of which were rescued by subsequent YAP overexpression. Conversely, constitutive KIBRA knockout mice displayed reduced phosphorylated YAP and increased YAP expression at baseline. These mice were protected from acute podocyte foot process effacement following protamine sulfate perfusion. KIBRA knockdown podocytes were also protected against protamine-induced injury. These findings suggest an important role for KIBRA in the pathogenesis of podocyte injury and the progression of proteinuric kidney disease.

The Hippo signaling pathway is an evolutionarily conserved kinase cascade, playing multiple roles in embryonic development that controls organ size, cell proliferation, and apoptosis. At the center of this network lie the Hippo kinase target and downstream pathway effector Yes-associated protein (YAP) and its paralog TAZ. In its phosphorylated form, cytoplasmic YAP is sequestered in an inactive state. When it is dephosphorylated, YAP, a potent oncogene, is activated and relocates to the nucleus to interact with a number of transcription factors and signaling regulators that promote cell growth, differentiation, and survival. The identification of YAP activation in human cancers has made it an attractive target for chemotherapeutic drug development. Little is known to date about the function of the Hippo pathway in the kidney, but that is rapidly changing. Recent studies have shed light on the role of Hippo-YAP signaling in glomerular and lower urinary tract embryonic development, maintenance of podocyte homeostasis, the integrity of the glomerular filtration barrier, regulation of renal tubular cyst growth, renal epithelial injury in diabetes, and renal fibrogenesis. This review summarizes the current knowledge of the Hippo-YAP signaling axis in the kidney under normal and disease conditions.

In contrast to artificial sweeteners, there are no reported negative health consequences of Stevia, such as toxicity, teratogenicity, mutagenicity or carcinogenicity. In contrast, the anti-hyperglycemic, antioxidant and antihypertensive properties of stevioside have been well documented, suggesting a potential medicinal use as an adjunctive treatment for several diseases. Anti-hyperglycemic PropertiesStevia glycosides have been widely shown to prevent weight gain and decrease serum glucose levels in animal and human models. As with any zero-calorie sweetener, stevia lacks calories and reduces serum glucose levels that typically rise about 1 hour after carbohydrate consumption, compared to sucrose. However, a 2010 study by Kujur et al. found that stevia significantly reduces mean serum glucose levels in subjects over a 1-month period. The study used Wister rats with diabetes induced by 5% alloxan monohydrate, and found that administering 50 mg/kg and 100 mg/kg of stevia daily resulted in significant time-dependent anti-hyperglycemic effects. When treated with 50 mg/kg of stevia in the aqueous, ether and methanolic extracts for 28 days, mean serum glucose levels fell from 220 to 161 mg/dL; 220 to 171 mg/dL; and 232to 163mg/dL, respectively. When treated with 100 mg/kg of the stevia extracts, mean serum glucose levels fell from 220 to 137 mg/dL; 209 to 168 mg/dL; and 218 to 181 mg/dL, respectively. There were non-significant differences in serum glucose levels between the 50mg/kg and 100mg/kg doses. Rats administered glyburide, a known oral diabetes medication that was used as a positive control, hada reduction in mean serum glucose levels from 211 to 101 mg/dL after 28 days. Thus, the administration of stevia

Sleep plays a pivotal role in both physical and mental health. Sleepqualitycan be affected by many socio demographic factors, such as race and/or ethnicity, as well as socio economic status (SES). Chronic sleep deprivation is associated with unhealthy behaviors such as alcohol abuse and also places individuals at risk for chronic diseases including obesity, cardiovasculardisease (CVD), depression, and/or anxiety. This review explores the common socio demographic factors and SES that can lead to sleep disturbances. Among these factors are shift work, poor dietary habits, smoking and alcohol abuse. Such factors need to be considered by health care providers in the clinical assessment and management plans of patients with sleep disorders.

Marijuana is the most common drug of abuse in the United States. Marijuana has more than 460 active chemical compounds including δ-9- tetrahydrocannabinol (THC). It acts via the CB1 and CB2 receptors that are distributed in various tissues in the body. Marijuana is known to cause tachycardia, bradycardia, hypertension, to decrease time angina, myocardial infarction and cardiac arrest. Till date, four cases of myocarditis/perimyocarditis associated with marijuana use have been reported. In one such case, it led to the development of heart failure in a young male patient. It is not clear if marijuana in and of itself causes myocarditis/perimyocarditis or if the etio-pathogenesis is actually related to the contaminants in marijuana such as pesticides and heavy metals. We hereby present a young male who with myocarditis related to marijuana use. Clinicians should have suspicion for myocarditis or perimyocarditis in patients presenting with chest pain following marijuana use.