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https://read.qxmd.com/read/30765727/mg132-protects-against-renal-dysfunction-by-regulating-akt-mediated-inflammation-in-diabetic-nephropathy
#1
Wei Zeng, Wei Qi, Jiao Mu, Yi Wei, Li-Ling Yang, Qian Zhang, Qiong Wu, Jian-Ying Tang, Bing Feng
Diabetic nephropathy (DN), the leading cause of end-stage renal disease (ESRD). To date, mounting evidence has shown that inflammation may contribute to the pathogenesis of DN. Recent reports have shown that proteasome inhibitors display cytoprotection by reducing the phosphorylation of Akt, a serine/threonine kinase, plays a critical role in cellular survival and metabolism and can crosstalk with inflammation. Therefore, we hypothesized that MG132, specific proteasome inhibitor, could provide renoprotection by suppressing Akt-mediated inflammation in DN...
February 14, 2019: Scientific Reports
https://read.qxmd.com/read/30759025/direct-and-indirect-inhibition-of-the-circadian-clock-protein-per1-effects-on-enac-and-blood-pressure
#2
Abdel A Alli, Ling Yu, Meaghan Rayann Holzworth, Jacob Richards, Kit-Yan Cheng, I Jeanette Lynch, Charles S Wingo, Michelle L Gumz
Circadian rhythms govern physiological functions and are important for overall health. The molecular circadian clock is comprised of several transcription factors that mediate circadian control of physiological function in part by regulating gene expression in a tissue-specific manner. These connections are well established but the underlying mechanisms are incompletely understood. The overall goal of this study was to examine the connection between the circadian clock protein Per1, ENaC, and BP using a multi-pronged approach...
February 13, 2019: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/30746723/pharmacokinetics-pharmacodynamics-and-safety-of-moss-agalactosidase-a-in-patients-with-fabry-disease
#3
Julia B Hennermann, Laila Arash-Kaps, György Fekete, Andreas Schaaf, Andreas Busch, Thomas Frischmuth
Moss-aGalactosidase A (moss-aGal) is a moss-derived version of human α-galactosidase developed for enzyme replacement therapy in patients with Fabry disease. It exhibits a homogenous N-glycosylation profile with >90% mannose-terminated glycans. In contrast to mammalian cell produced α-galactosidase, moss-aGal does not rely on mannose-6-phosphate receptor mediated endocytosis but targets the mannose receptor for tissue uptake. We conducted a phase 1 clinical trial with moss-aGal in six patients with confirmed diagnosis of Fabry disease during a 28-day schedule...
January 12, 2019: Journal of Inherited Metabolic Disease
https://read.qxmd.com/read/30734886/spironolactone-alleviates-diabetic-nephropathy-through-promoting-autophagy-in-podocytes
#4
Dan Dong, Ting-Ting Fan, Ying-Shi Ji, Jin-Yu Yu, Shan Wu, Li Zhang
PURPOSE: Podocytes are terminally differentiated cells lining the Bowman's capsule. Podocytes are critical for the proper glomerular filtration barrier function. At the same time, autophagy is crucial for maintaining podocyte homeostasis and insufficient autophagy could cause podocyte loss and proteinuria that is commonly observed in diabetic nephropathy (DN). METHODS: In this study, we investigated the role of spironolactone in podocyte loss and autophagy. DN model was established in male Sprague-Dawley rats using high-fat diet and low-dose streptozotocin...
February 8, 2019: International Urology and Nephrology
https://read.qxmd.com/read/30733880/high-lyso-gb3-plasma-levels-associated-with-decreased-mir-29-and-mir-200-urinary-excretion-in-young-non-albuminuric-male-patient-with-classic-fabry-disease
#5
Sebastián Jaurretche, Germán R Perez, Graciela Venera
Renal involvement is associated with a greater morbidity and mortality in Fabry disease. Pathological albuminuria, the first Fabry nephropathy clinical manifestation, can occur from early childhood, although histological lesions such as tubulo-interstitial fibrosis and glomerulosclerosis are present or may precede the onset of pathological albuminuria. In renal cells, exposure to Lyso-Gb3 is correlated with increased expression of Transforming Growth Factor- β eta (TGF- β ). miR-21, miR-192, and miR-433 that promote fibrosis are activated by TGF- β , and miR-29 and miR-200 that suppress fibrosis are inhibited by TGF- β ...
2019: Case Reports in Nephrology
https://read.qxmd.com/read/30724104/renal-sodium-excretion-consequent-to-pharmacogenetic-activation-of-gq-dreadd-in-principal-cells
#6
Elena Mironova, Faroug Suliman, James D Stockand
Stimulation of Gq-coupled metabotropic P2Y2 receptors decrease the activity of ENaC in renal principal cells of the distal nephron. The physiological consequences of disrupting P2Y2 receptor signaling in the P2Y2 receptor knockout mouse are decreased sodium excretion and increased arterial blood pressure. However, because of the global nature of this knockout model, the quantitative contribution of ENaC and the distal nephron versus that of upstream renal vascular and tubular elements to changes in urinary excretion and arterial blood pressure are obscure...
February 6, 2019: American Journal of Physiology. Renal Physiology
https://read.qxmd.com/read/30721337/hyperuricemia-urine-uric-excretion-and-associated-complications-in-thalassemia-patients
#7
Juthatip Chaloemwong, Adisak Tantiworawit, Thanawat Rattanathammethee, Chatree Chai-Adisaksopha, Ekarat Rattarittamrong, Lalita Norasetthada, Pimlak Charoenkwan, Worawit Louthrenoo
Thalassemia patients have a high cell turnover rate due to chronic hemolysis and ineffective erythropoiesis; therefore, hyperuricemia is anticipated. This study aimed to identify the prevalence of hyperuricemia, gout and nephrolithiasis, conditions associated with serum uric acid (SUA), and urine uric acid excretion (UUA) in thalassemia patients. This was a cross-sectional study in patients aged 15 years or older at Chiang Mai University Hospital. All patients had blood and 24-h urine collection test. We enrolled 112 thalassemia patients in which 67...
February 5, 2019: Annals of Hematology
https://read.qxmd.com/read/30712199/cefiderocol-a-siderophore-cephalosporin-with-activity-against-carbapenem-resistant-and-multidrug-resistant-gram-negative-bacilli
#8
REVIEW
George G Zhanel, Alyssa R Golden, Sheryl Zelenitsky, Karyn Wiebe, Courtney K Lawrence, Heather J Adam, Temilolu Idowu, Ronald Domalaon, Frank Schweizer, Michael A Zhanel, Philippe R S Lagacé-Wiens, Andrew J Walkty, Ayman Noreddin, Joseph P Lynch Iii, James A Karlowsky
Cefiderocol is an injectable siderophore cephalosporin discovered and being developed by Shionogi & Co., Ltd., Japan. As with other β-lactam antibiotics, the principal antibacterial/bactericidal activity of cefiderocol occurs by inhibition of Gram-negative bacterial cell wall synthesis by binding to penicillin binding proteins; however, it is unique in that it enters the bacterial periplasmic space as a result of its siderophore-like property and has enhanced stability to β-lactamases. The chemical structure of cefiderocol is similar to both ceftazidime and cefepime, which are third- and fourth-generation cephalosporins, respectively, but with high stability to a variety of β-lactamases, including AmpC and extended-spectrum β-lactamases (ESBLs)...
February 2, 2019: Drugs
https://read.qxmd.com/read/30699330/telmisartan-attenuates-diabetic-nephropathy-progression-by-inhibiting-the-dimerization-of-angiotensin-type-1-receptor-and-adiponectin-receptor-1
#9
Dongqing Zha, Tao Yao, Liping Bao, Ping Gao, Xiaoyan Wu
AIMS: The heterodimerization of angiotensin II receptors (AT1R and AT2R) with adiponectin receptor AdipoR1 and AdipoR2 may instigate high glucose (HG)-induced renal tubulointerstitial injury. This study examined the effect of telmisartan on diabetic nephropathy (DN) and its underlying mechanism. MAIN METHODS: Diabetes was induced in rats through a single intraperitoneal injection of streptozotocin. Diabetic rats treated with or without the intravenous injection of AdipoR1 siRNA were intragastrically administered with 5 mg/kg/d telmisartan or a vehicle for 12 weeks...
January 27, 2019: Life Sciences
https://read.qxmd.com/read/30682139/influence-of-long-term-administration-of-tofogliflozin-on-chronic-inflammation-of-visceral-adipose-tissue-in-mice-with-obesity-induced-by-a-high-fat-diet
#10
Kohsuke Shirakawa, Wataru Yano, Keisuke Inoue, Yoshinori Katsumata, Jin Endo, Motoaki Sano
We previously found that senescence of cluster of differentiation 4 (CD4) T cells is accelerated in the visceral adipose tissue (VAT) of mice with diet-induced obesity (DIO) due to a high-fat diet (HFD), and that these senescent-associated T cells cause chronic inflammation of visceral adipose tissue through secretion of osteopontin, provoking systemic insulin resistance. In this study, we examined whether the development of chronic inflammation and senescence-associated T cells in VAT of DIO mice was improved by long-term weight loss after switching to normal chow (NC) or by administration of a sodium glucose cotransporter 2 inhibitor (tofogliflozin)...
2019: PloS One
https://read.qxmd.com/read/30677083/epidermal-growth-factor-and-its-influencing-variables-in-healthy-children-and-adults
#11
Sarang Meybosch, Amandine De Monie, Charlotte Anné, Luc Bruyndonckx, Angelika Jürgens, Benedicte Y De Winter, Dominique Trouet, Kristien J Ledeganck
BACKGROUND & OBJECTIVE: Epidermal growth factor (EGF) stimulates cell proliferation and differentiation after binding to its receptor. Next to its role in magnesium homeostasis, EGF disturbances have been described in oncology, diabetes and autism spectrum disorders. The aim of this study was to determine EGF serum and urine values for both healthy children and adults. Next, we investigated the relation between several variables and urinary and serum EGF concentrations. METHODS: Both healthy adults (n = 50) and children (n = 78) were included...
2019: PloS One
https://read.qxmd.com/read/30664212/participation-of-the-angii-trpc6-nfat-axis-in-the-pathogenesis-of-podocyte-injury-in-rats-with-type-2-diabetes
#12
Ruixia Ma, Yan Xu, Hanyan Zhou, Di Zhang, Dandan Yao, Limin Song, Yuan Liu
The canonical transient receptor potential channel 6 ion channel is expressed in podocytes and is an important component of the glomerular slit diaphragm. Focal segmental glomerulosclerosis is closely associated with TRPC6 gene mutations, and TRPC6 mediates podocyte injury induced by high glucose. Angiotensin II (AngII) has been revealed to enhance TRPC6 currents in certain types of cells, including podocytes and ventricular myocytes. It has been reported that glucose regulated TRPC6 expression in an AngII‑dependent manner in podocytes and that this pathway is critical in diabetic nephropathy...
January 17, 2019: Molecular Medicine Reports
https://read.qxmd.com/read/30651324/an-engineered-e-coli-nissle-improves-hyperammonemia-and-survival-in-mice-and-shows-dose-dependent-exposure-in-healthy-humans
#13
Caroline B Kurtz, Yves A Millet, Marja K Puurunen, Mylène Perreault, Mark R Charbonneau, Vincent M Isabella, Jonathan W Kotula, Eugene Antipov, Yossi Dagon, William S Denney, David A Wagner, Kip A West, Andrew J Degar, Aoife M Brennan, Paul F Miller
The intestine is a major source of systemic ammonia (NH3 ); thus, capturing part of gut NH3 may mitigate disease symptoms in conditions of hyperammonemia such as urea cycle disorders and hepatic encephalopathy. As an approach to the lowering of blood ammonia arising from the intestine, we engineered the orally delivered probiotic Escherichia coli Nissle 1917 to create strain SYNB1020 that converts NH3 to l-arginine (l-arg). We up-regulated arginine biosynthesis in SYNB1020 by deleting a negative regulator of l-arg biosynthesis and inserting a feedback-resistant l-arg biosynthetic enzyme...
January 16, 2019: Science Translational Medicine
https://read.qxmd.com/read/30635937/slc13a3-variants-cause-acute-reversible-leukoencephalopathy-and-%C3%AE-kg-accumulation
#14
Joseph P Dewulf, Elsa Wiame, Imen Dorboz, Monique Elmaleh-Bergès, Apolline Imbard, Dana Dumitriu, Malgorzata Rak, Agnès Bourillon, Raphaël Helaers, Alisha Malla, Florence Renaldo, Odile Boespflug-Tanguy, Marie-Françoise Vincent, Jean-François Benoist, Ron A Wevers, Avner Schlessinger, Emile Van Schaftingen, Marie-Cécile Nassogne, Manuel Schiff
OBJECTIVE: SLC13A3 encodes the plasma membrane Na+ /Dicarboxylate Cotransporter 3 (NaDC3), which imports inside the cell four to six carbon dicarboxylates as well as N-acetylaspartate (NAA). SLC13A3 is mainly expressed in kidney, in astrocytes and in the choroid plexus. We describe two unrelated patients presenting with acute, reversible (and recurrent in one) neurological deterioration during a febrile illness. Both patients exhibited a reversible leukoencephalopathy and a markedly increased and persisting over time urinary excretion of α-ketoglutarate (αKG)...
January 11, 2019: Annals of Neurology
https://read.qxmd.com/read/30635033/clazakizumab-in-late-antibody-mediated-rejection-study-protocol-of-a-randomized-controlled-pilot-trial
#15
Farsad Eskandary, Michael Dürr, Klemens Budde, Konstantin Doberer, Roman Reindl-Schwaighofer, Johannes Waiser, Markus Wahrmann, Heinz Regele, Andreas Spittler, Nils Lachmann, Christa Firbas, Jakob Mühlbacher, Gregor Bond, Philipp F Halloran, Edward Chong, Bernd Jilma, Georg A Böhmig
BACKGROUND: Late antibody-mediated rejection (ABMR) triggered by donor-specific antibodies (DSA) is a cardinal cause of kidney allograft dysfunction and loss. Diagnostic criteria for this rejection type are well established, but effective treatment remains a major challenge. Recent randomized controlled trials (RCT) have failed to demonstrate the efficacy of widely used therapies, such as rituximab plus intravenous immunoglobulin or proteasome inhibition (bortezomib), reinforcing a great need for new therapeutic concepts...
January 11, 2019: Trials
https://read.qxmd.com/read/30608204/8-aminoguanine-induces-diuresis-natriuresis-and-glucosuria-by-inhibiting-purine-nucleoside-phosphorylase-and-reduces-potassium-excretion-by-inhibiting-rac1
#16
Edwin K Jackson, Zaichuan Mi, Thomas R Kleyman, Dongmei Cheng
Background 8-Aminoguanosine and 8-aminoguanine are K+ -sparing natriuretics that increase glucose excretion. Most effects of 8-aminoguanosine are due to its metabolism to 8-aminoguanine. However, the mechanism by which 8-aminoguanine affects renal function is unknown and is the focus of this investigation. Methods and Results Because 8-aminoguanine has structural similarities with inhibitors of the epithelial sodium channel (ENaC), Na+ /H+ exchangers, and adenosine A1 receptors, we examined the effects of 8-aminoguanine on EN aC activity in mouse collecting duct cells, on intracellular pH of human proximal tubular epithelial cells, on responses to a selective A1 -receptor agonist in vivo, and on renal excretory function in A1 -receptor knockout rats...
November 6, 2018: Journal of the American Heart Association
https://read.qxmd.com/read/30596515/tubular-flow-activates-magnesium-transport-in-the-distal-convoluted-tubule
#17
Eric H J Verschuren, Joost G J Hoenderop, Dorien J M Peters, Francisco J Arjona, René J M Bindels
Magnesium (Mg2+ ) is an important cofactor of many enzymes crucial for life; therefore, maintaining a Mg2+ balance in the body is essential. In the kidney, the distal convoluted tubule (DCT) determines the final urinary Mg2+ excretion. The nephron is subjected to variable urinary flow, but little is known about the influence of flow on Mg2+ transport. Primary cilia, which are mechanosensory organelles that sense changes in flow, are expressed on tubular epithelial cells. This study aimed to elucidate whether urinary flow facilitates DCT Mg2+ transport...
December 31, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://read.qxmd.com/read/30588151/improving-outcomes-for-patients-with-distal-renal-tubular-acidosis-recent-advances-and-challenges-ahead
#18
REVIEW
Toru Watanabe
Primary distal renal tubular acidosis (dRTA) is a rare genetic disorder caused by impaired distal acidification due to a failure of type A intercalated cells (A-ICs) in the collecting tubule. dRTA is characterized by persistent hyperchloremia, a normal plasma anion gap, and the inability to maximally lower urinary pH in the presence of systemic metabolic acidosis. Common clinical features of dRTA include vomiting, failure to thrive, polyuria, hypercalciuria, hypocitraturia, nephrocalcinosis, nephrolithiasis, growth delay, and rickets...
2018: Pediatric Health, Medicine and Therapeutics
https://read.qxmd.com/read/30571558/norepinephrine-induced-stimulation-of-kir4-1-kir5-1-is-required-for-the-activation-of-nacl-transporter-in-distal-convoluted-tubule
#19
Xin-Peng Duan, Li Gu, Yu Xiao, Zhong-Xiuzi Gao, Peng Wu, Yun-Hong Zhang, Xin-Xin Meng, Jun-Lin Wang, Dan-Dan Zhang, Dao-Hong Lin, Wen-Hui Wang, Ruimin Gu
The stimulation of β-adrenergic receptor increases thiazide-sensitive NaCl cotransporter (NCC), an effect contributing to salt-sensitive hypertension by sympathetic stimulation. We now test whether the stimulation of β-adrenergic receptor-induced activation of NCC is achieved through activating basolateral Kir4.1 in the distal convoluted tubule (DCT). Application of norepinephrine increased the basolateral 40 pS K+ channel (Kir4.1/Kir5.1 heterotetramer) in the DCT. The stimulatory effect of norepinephrine on the K+ channel was mimicked by cAMP analogue but abolished by inhibiting PKA (protein kinase A)...
January 2019: Hypertension
https://read.qxmd.com/read/30554341/renoprotective-effects-of-the-novel-prostaglandin-ep4-receptor-selective-antagonist-asp7657-in-5-6-nephrectomized-chronic-kidney-disease-rats
#20
Kazuhiko Mizukami, Hiroyuki Yoshida, Eisuke Nozawa, Koichi Wada, Tohru Ugawa
Prostaglandins (PGs) are important lipid mediators of numerous physiologic and pathophysiologic processes in the kidney. PGE2 , the most abundant renal PG, plays a major role in renal physiology, including renin release and glomerular hemodynamics. We investigated the renoprotective properties of the novel PGE2 EP4 receptor-selective antagonist ASP7657 in 5/6 nephrectomized rats, a chronic kidney disease (CKD) model. Eight weeks of repeated administration of ASP7657 (0.001-0.1 mg/kg) dose-dependently and significantly reduced urinary protein excretion and attenuated the development of glomerulosclerosis and tubulointerstitial damage, including fibrosis and inflammatory cell infiltration, without affecting blood pressure...
December 15, 2018: Naunyn-Schmiedeberg's Archives of Pharmacology
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