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https://www.readbyqxmd.com/read/29445145/canagliflozin-mediated-dual-inhibition-of-mitochondrial-glutamate-dehydrogenase-and-complex-i-an-off-target-adverse-effect
#1
Philipp F Secker, Sascha Beneke, Nadja Schlichenmaier, Johannes Delp, Simon Gutbier, Marcel Leist, Daniel R Dietrich
Recent FDA Drug Safety Communications report an increased risk for acute kidney injury in patients treated with the gliflozin class of sodium/glucose co-transport inhibitors indicated for treatment of type 2 diabetes mellitus. To identify a potential rationale for the latter, we used an in vitro human renal proximal tubule epithelial cell model system (RPTEC/TERT1), physiologically representing human renal proximal tubule function. A targeted metabolomics approach, contrasting gliflozins to inhibitors of central carbon metabolism and mitochondrial function, revealed a double mode of action for canagliflozin, but not for its analogs dapagliflozin and empagliflozin...
February 14, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29444905/renal-interstitial-platelet-derived-growth-factor-receptor-%C3%AE-cells-support-proximal-tubular-regeneration
#2
Ina Maria Schiessl, Alexandra Grill, Katharina Fremter, Dominik Steppan, Maj-Kristina Hellmuth, Hayo Castrop
BACKGROUND: The kidney is considered to be a structurally stable organ with limited baseline cellular turnover. Nevertheless, single cells must be constantly replaced to conserve the functional integrity of the organ. PDGF chain B (PDGF-BB) signaling through fibroblast PDGF receptor- β (PDGFR β ) contributes to interstitial-epithelial cell communication and facilitates regenerative functions in several organs. However, the potential role of interstitial cells in renal tubular regeneration has not been examined...
February 14, 2018: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/29439807/could-notch-signaling-pathway-be-a-potential-therapeutic-option-in-renal-diseases
#3
Laura Marquez-Exposito, Elena Cantero-Navarro, Carolina Lavoz, Marta Fierro-Fernández, Jonay Poveda, Sandra Rayego-Mateos, Raúl R Rodrigues-Diez, José Luis Morgado-Pascual, Macarena Orejudo, Sergio Mezzano, Marta Ruiz-Ortega
Notch pathway regulates key processes in the kidney, involved in embryonic development and tissue damage. In many human chronic renal diseases a local activation of Notch pathway has been described, suggesting that several components of Notch pathway could be considered as biomarkers of renal damage. Experimental studies by genetic modulation of Notch components or pharmacological approaches by γ-secretase inhibitors have demonstrated the role of this pathway in renal regeneration renal, podocyte apoptosis, proliferation and fibroblasts activation, and induction of epithelial to mesenchymal transition of tubular epithelial cells...
February 10, 2018: Nefrología: Publicación Oficial de la Sociedad Española Nefrologia
https://www.readbyqxmd.com/read/29407000/the-arteriolar-injury-in-hypertension
#4
Qian Ru Gu, Yang Yang Li, Guo Rong Chen, M J Quinn
In 1937, Drs. Moritz and Oldt described arteriolar injuries in the kidneys (and other viscera) in hypertension, across the age range, in both sexes, and, in different races. This hypothesis proposes that injuries to vasomotor nerves cause the arteriolar injury in the kidney in hypertension, (as well as that in the uterus in preeclampsia). Different patterns of perivascular hyalinisation in different viscera are clues to the varying causes and consequences of arteriolar injury. In the uterus there is a symmetrical, perivascular "halo of hyalinisation" that marks the lines of extension of regenerating, injured nerves to the placental bed, whereas in the kidney there is a disordered and asymmetrical "halo of hyalinisation" where persistent, and recurrent, increases in intravascular pressures interrupt development of regenerating nerves...
February 2018: Medical Hypotheses
https://www.readbyqxmd.com/read/29389516/wnt-signaling-in-kidney-development-and-disease
#5
Yongping Wang, Chengji J Zhou, Youhua Liu
Wnt signal cascade is an evolutionarily conserved, developmental pathway that regulates embryogenesis, injury repair, and pathogenesis of human diseases. It is well established that Wnt ligands transmit their signal via canonical, β-catenin-dependent and noncanonical, β-catenin-independent mechanisms. Mounting evidence has revealed that Wnt signaling plays a key role in controlling early nephrogenesis and is implicated in the development of various kidney disorders. Dysregulations of Wnt expression cause a variety of developmental abnormalities and human diseases, such as congenital anomalies of the kidney and urinary tract, cystic kidney, and renal carcinoma...
January 2018: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/29380818/renin-cells-in-homeostasis-regeneration-and-immune-defence-mechanisms
#6
REVIEW
R Ariel Gomez, Maria Luisa S Sequeira-Lopez
An accumulating body of evidence suggests that renin-expressing cells have developed throughout evolution as a mechanism to preserve blood pressure and fluid volume homeostasis as well as to counteract a number of homeostatic and immunological threats. In the developing embryo, renin precursor cells emerge in multiple tissues, where they differentiate into a variety of cell types. The function of those precursors and their progeny is beginning to be unravelled. In the developing kidney, renin-expressing cells control the morphogenesis and branching of the renal arterial tree...
January 30, 2018: Nature Reviews. Nephrology
https://www.readbyqxmd.com/read/29380564/in-situ-tissue-regeneration-of-renal-tissue-induced-by-collagen-hydrogel-injection
#7
Sang Jin Lee, Hung-Jen Wang, Tae-Hyoung Kim, Jin San Choi, Gauri Kulkarni, John D Jackson, Anthony Atala, James J Yoo
Host stem/progenitor cells can be mobilized and recruited to a target location using biomaterials, and these cells may be used for in situ tissue regeneration. The objective of this study was to investigate whether host biologic resources could be used to regenerate renal tissue in situ. Collagen hydrogel was injected into the kidneys of normal mice, and rat kidneys that had sustained ischemia/reperfusion injury. After injection, the kidneys of both animal models were examined up to 4 weeks for host tissue response...
February 2018: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/29377486/liver-atrophy-and-regeneration-in-non-cirrhotic-portal-vein-thrombosis-effect-of-surgical-shunts
#8
Abdulrhman S Elnaggar, Adam D Griesemer, Stuart Bentley-Hibbert, Robert S Brown, Mercedes Martinez, Steven J Lobritto, Tomoaki Kato, Jean C Emond
OBJECTIVE: To characterize the relationship between portal vein thrombosis (PVT) and hepatic atrophy in the non-cirrhotic patients and the effect of various types of surgical shunts on liver regeneration and splenomegaly. BACKGROUND: Non-cirrhotic patients with PVT suffer from presinusoidal portal hypertension and often hepatic atrophy, a topic that has received little attention. We hypothesized that patients with PVT have decreased liver volumes, and shunts that preserve intrahepatic portal flow enhance liver regeneration...
January 29, 2018: Liver Transplantation
https://www.readbyqxmd.com/read/29357199/creatine-kinase-and-renal-sodium-excretion-in-african-and-european-men-on-a-high-sodium-diet
#9
Lizzy M Brewster, Inge Oudman, Rani V Nannan Panday, Inna Khoyska, Yentl C Haan, Fares A Karamat, Joseph F Clark, Gert A van Montfrans
Creatine kinase (CK) rapidly regenerates ATP for Na+ /K+ -ATPase driven sodium retention throughout the kidney. Therefore, we assessed whether resting plasma CK is associated with sodium retention after a high sodium diet. Sixty healthy men (29 European and 31 African ancestry) with a mean age of 37.2 years (SE 1.2) were assigned to low sodium intake (< 50 mmol/d) during 7 days, followed by 3 days of high sodium intake (> 200 mmol/d). Sodium excretion (mmol/24-h) after high sodium was 260.4 (28...
January 22, 2018: Journal of Clinical Hypertension
https://www.readbyqxmd.com/read/29291552/carvacrol-attenuates-histopathogic-and-functional-impairments-induced-by-bilateral-renal-ischemia-reperfusion-in-rats
#10
Hulya Ozturk, Ayhan Cetinkaya, Selma Erdogan Duzcu, Buket Kin Tekce, Hayrettin Ozturk
BACKGROUND: Renal ischemia/reperfusion injury is the most common cause of acute kidney injury, which frequent occurrence in critically ill patients. OBJECTIVES: The aim of this study was to investigate the role of Carvacrol (CARV) against bilateral ischemia reperfusion (I/R) in rats. METHODS: Renal I/R injury were induced by clamping of the left and right renal arteries for 45 min followed by 24 h of reperfusion. Thirty male Sprague-Dawley rats were randomly allocated to three groups (n = 10): the sham-control group, the renal I/R-untreated (I/R-untreated) group, and the I/R-CARV-treated group...
December 29, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29237753/troy-tnfrsf19-marks-epithelial-progenitor-cells-during-mouse-kidney-development-that-continue-to-contribute-to-turnover-in-adult-kidney
#11
Frans Schutgens, Maarten B Rookmaaker, Francis Blokzijl, Ruben van Boxtel, Robert Vries, Edwin Cuppen, Marianne C Verhaar, Hans Clevers
During kidney development, progressively committed progenitor cells give rise to the distinct segments of the nephron, the functional unit of the kidney. Similar segment-committed progenitor cells are thought to be involved in the homeostasis of adult kidney. However, markers for most segment-committed progenitor cells remain to be identified. Here, we evaluate Troy/TNFRSF19 as a segment-committed nephron progenitor cell marker. Troy is expressed in the ureteric bud during embryonic development. During postnatal nephrogenesis, Troy+ cells are present in the cortex and papilla and display an immature tubular phenotype...
December 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29237235/efficacy-and-safety-of-everolimus-with-reduced-tacrolimus-in-living-donor-liver-transplant-recipients-12-month-results-of-a-randomized-multicenter-study
#12
Long-Bin Jeng, Sung Gyu Lee, Arvinder Singh Soin, Wei-Chen Lee, Kyung-Suk Suh, Dong Jin Joo, Shinji Uemoto, Jaewon Joh, Tomoharu Yoshizumi, Horng-Ren Yang, Gi-Won Song, Patricia Lopez, Jossy Kochuparampil, Carole Sips, Shuhei Kaneko, Gary Levy
In a multicenter, open-label, study, 284 living-donor liver transplant patients were randomized at 30±5 days post-transplant to start everolimus+reduced tacrolimus (EVR+rTAC) or continue standard tacrolimus (TAC Control). EVR+rTAC was non-inferior to TAC Control for the primary efficacy endpoint of treated BPAR, graft loss or death at 12 months post-transplant: difference -0.7% [90%CI -5.2%, 3.7%]; p<0.001 for non-inferiority. tBPAR occurred in 2.2% and 3.6% of patients, respectively. The key secondary endpoint, change in estimated GFR from randomization to month 12, achieved non-inferiority (p<0...
December 13, 2017: American Journal of Transplantation
https://www.readbyqxmd.com/read/29224095/sex-differences-in-muscle-wasting
#13
Lindsey J Anderson, Haiming Liu, Jose M Garcia
With aging and other muscle wasting diseases, men and women undergo similar pathological changes in skeletal muscle: increased inflammation, enhanced oxidative stress, mitochondrial dysfunction, satellite cell senescence, elevated apoptosis and proteasome activity, and suppressed protein synthesis and myocyte regeneration. Decreased food intake and physical activity also indirectly contribute to muscle wasting. Sex hormones also play important roles in maintaining skeletal muscle homeostasis. Testosterone is a potent anabolic factor promoting muscle protein synthesis and muscular regeneration...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29221627/alkaline-diet-and-metabolic-acidosis-practical-approaches-to-the-nutritional-management-of-chronic-kidney-disease
#14
Larissa Rodrigues Neto Angéloco, Gabriela Cristina Arces de Souza, Elen Almeida Romão, Paula Garcia Chiarello
The kidneys play an extremely important role in maintaining the body acid-base balance by excreting nonvolatile acids and regenerating and reabsorbing bicarbonate in the kidney tubules. As the individual loses their kidney function, renal excretion of nonvolatile acid produced by metabolism of the diet is impaired, resulting in low-grade metabolic acidosis. With this in mind, it is relevant to better understand the dietary aspects related to the acid-base balance in chronic kidney disease metabolic acidosis and try to provide possible strategies for the nutritional management of these cases...
December 5, 2017: Journal of Renal Nutrition
https://www.readbyqxmd.com/read/29198839/sox9-activation-is-involved-in-tubule-repair-after-unilateral-partial-nephrectomy
#15
Qiwang Ma, Yujia Wang, Wei Zuo
AIMS: Tubule repair has been noticed after kidney tissue damage, however the cellular mechanism behind remains unclear. Here we successfully constructed a mouse unilateral partial nephrectomy model mimicking renal carcinoma surgery, and further investigated whether this procedure triggered regenerative action. MAIN METHODS: We used the unilateral partial nephrectomy model to study kidney repair. Kidney function after nephrectomy was measured using creatinine and urea nitrogen assay kit...
November 30, 2017: Life Sciences
https://www.readbyqxmd.com/read/29187247/improvement-of-renal-function-after-human-umbilical-cord-mesenchymal-stem-cell-treatment-on-chronic-renal-failure-and-thoracic-spinal-cord-entrapment-a-case-report
#16
Ahmad Jabir Rahyussalim, Ifran Saleh, Tri Kurniawati, Andi Praja Wira Yudha Lutfi
BACKGROUND: Chronic renal failure is an important clinical problem with significant socioeconomic impact worldwide. Thoracic spinal cord entrapment induced by a metabolic yield deposit in patients with renal failure results in intrusion of nervous tissue and consequently loss of motor and sensory function. Human umbilical cord mesenchymal stem cells are immune naïve and they are able to differentiate into other phenotypes, including the neural lineage. Over the past decade, advances in the field of regenerative medicine allowed development of cell therapies suitable for kidney repair...
November 30, 2017: Journal of Medical Case Reports
https://www.readbyqxmd.com/read/29181712/exosomes-and-microvesicles-in-normal-physiology-pathophysiology-and-renal-diseases
#17
REVIEW
Anne-Lie Ståhl, Karl Johansson, Maria Mossberg, Robin Kahn, Diana Karpman
Extracellular vesicles are cell-derived membrane particles ranging from 30 to 5,000 nm in size, including exosomes, microvesicles, and apoptotic bodies. They are released under physiological conditions, but also upon cellular activation, senescence, and apoptosis. They play an important role in intercellular communication. Their release may also maintain cellular integrity by ridding the cell of damaging substances. This review describes the biogenesis, uptake, and detection of extracellular vesicles in addition to the impact that they have on recipient cells, focusing on mechanisms important in the pathophysiology of kidney diseases, such as thrombosis, angiogenesis, tissue regeneration, immune modulation, and inflammation...
November 27, 2017: Pediatric Nephrology: Journal of the International Pediatric Nephrology Association
https://www.readbyqxmd.com/read/29170512/generation-of-interspecies-limited-chimeric-nephrons-using-a-conditional-nephron-progenitor-cell-replacement-system
#18
S Yamanaka, S Tajiri, T Fujimoto, K Matsumoto, S Fukunaga, B S Kim, H J Okano, T Yokoo
Animal fetuses and embryos may have applications in the generation of human organs. Progenitor cells may be an appropriate cell source for regenerative organs because of their safety and availability. However, regenerative organs derived from exogenous lineage progenitors in developing animal fetuses have not yet been obtained. Here, we established a combination system through which donor cells could be precisely injected into the nephrogenic zone and native nephron progenitor cells (NPCs) could be eliminated in a time- and tissue-specific manner...
November 23, 2017: Nature Communications
https://www.readbyqxmd.com/read/29160569/reconstruction-of-bladder-function-and-prevention-of-renal-deterioration-by-means-of-end-to-side-neurorrhaphy-in-rats-with-neurogenic-bladder
#19
Yun Long Li, Jian Jun Wen, Yi Bo Wen, Xiang Fei He, Jun Wei Wu, Yan Wei Li, Zhong Jiang Han, Jin Jin Feng, Shao Hua Yan, Shou Lin Li, John Pfa Heesakkers, Wan Sheng Gao, Jian Guo Wen
AIMS: To investigate the feasibility of restoring bladder function and prevention of renal deterioration by neurorrhaphy in rats with neurogenic bladder (NB). METHODS: Forty-two rats were assigned to the end-to-side nerve coaptation group (ECG, n = 16), no nerve coaptation group (NCG, n = 16), and control group (CG, n = 10). In the ECG, the left ventral root (VR) and dorsal root (DR) of L6 and S1 were transected, and the distal stump of L6VR was sutured to the lateral face of L4VR...
November 21, 2017: Neurourology and Urodynamics
https://www.readbyqxmd.com/read/29158085/generation-of-branching-ureteric-bud-tissues-from-human-pluripotent-stem-cells
#20
Shin-Ichi Mae, Makoto Ryosaka, Taro Toyoda, Kyoko Matsuse, Yoichi Oshima, Hiraku Tsujimoto, Shiori Okumura, Aya Shibasaki, Kenji Osafune
Recent progress in kidney regeneration research is noteworthy. However, the selective and robust differentiation of the ureteric bud (UB), an embryonic renal progenitor, from human pluripotent stem cells (hPSCs) remains to be established. The present study aimed to establish a robust induction method for branching UB tissue from hPSCs towards the creation of renal disease models. Here, we found that anterior intermediate mesoderm (IM) differentiates from anterior primitive streak, which allowed us to successfully develop an efficient two-dimensional differentiation method of hPSCs into Wolffian duct (WD) cells...
January 1, 2018: Biochemical and Biophysical Research Communications
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