A5100353418- Hormonal Regulation and Hypertension
- Ion Transport and Channel Regulation
- Dental Education, Practice, Research
- Ion channel regulation and function
- Estrogen and related hormone effects
- Cardiovascular, Neuropeptides, and Oxidative Stress Research
- Receptor Mechanisms and Signaling
- Neuroscience and Neuropharmacology Research
- Medical and Biological Sciences
- Electrolyte and hormonal disorders
- Health and Medical Research Impacts
- Digestive system and related health
- Family and Patient Care in Intensive Care Units
- Gastrointestinal motility and disorders
- Vascular Malformations Diagnosis and Treatment
- Congenital Heart Disease Studies
- Music and Audio Processing
- Geriatric Care and Nursing Homes
- Magnesium in Health and Disease
- Phonocardiography and Auscultation Techniques
- Health Literacy and Information Accessibility
- Global Health Workforce Issues
- Congenital heart defects research
- Helicobacter pylori-related gastroenterology studies
- Parathyroid Disorders and Treatments
Yale University
2013-2025
North University of China
2024
Southwest Medical University
2024
Howard Hughes Medical Institute
2008-2023
Anhui Medical University
2020-2022
Ministry of Education of the People's Republic of China
2022
First Affiliated Hospital of Anhui Medical University
2022
Ningbo No.6 Hospital
2021
The Affiliated Yongchuan Hospital of Chongqing Medical University
2018-2019
Chongqing Medical University
2018-2019
Primary aldosteronism is a leading cause of secondary hypertension (HTN), but the mechanisms underlying characteristic renin-independent secretion aldosterone remain unknown in most patients.We report new familial form father and two daughters. All were diagnosed with severe HTN refractory to medical treatment by age 7 yr. We performed variety clinical, biochemical, genetic studies attempt clarify molecular defect.Biochemical revealed hyporeninemia, hyperaldosteronism, very high levels...
Significance Loss of function mutations in the potassium channel KCNJ10 causes a salt-wasting syndrome. The phenotype resembles Gitelman syndrome, which results from loss sodium chloride transport along distal convoluted tubule (DCT), but mechanisms involved are not clear. Here, we perform experiments kidney Kcnj10 knockout mice and demonstrate that is main contributor to basolateral conductance DCT activity regulates expression ste20-related proline–alanine-rich kinase (SPAK) determines...
Variants with large effect contribute to congenital heart disease (CHD). To date, recessive genotypes (RGs) have commonly been implicated through anecdotal ascertainment of consanguineous families and candidate gene-based analysis; the contribution broad range CHD phenotypes has limited. We analyzed whole exome sequences 5,424 probands. Rare damaging RGs were estimated at least 2.2% CHD, greater enrichment among laterality (5.4%) versus other subsets (1.4%). Among 108 curated human genes,...
We recently demonstrated that delta-opioid receptor (DOR) activation protects cortical neurons against glutamate-induced injury. Because glutamate is a mediator of hypoxic injury in neurons, we hypothesized DOR involved neuroprotection during O2 deprivation and its activation/inhibition may alter neuronal susceptibility to stress. In this work, tested the effect opioid inhibition on cultured hypoxia (1% O2). Cell was assessed by lactate dehydrogenase release, morphology-based quantification,...
Ureteric bud (UB) branching during kidney development determines the final number of nephrons. Although hepatocyte growth factor and its receptor Met have been shown to stimulate morphogenesis in explanted embryonic kidneys, loss expression is lethal early embryogenesis without obvious abnormalities. Met(fl/fl);HoxB7-Cre mice, which lack selectively UB, were generated found a reduction nephron number. These mice increased Egf both adult kidney, exogenous can partially rescue defect seen...
Significance Aldosterone produces distinct adaptive responses in volume depletion and hyperkalemia. Mutations with-no-lysine (WNK) kinases or ubiquitin ligases containing Cullin 3 (CUL3) Kelch-like (KLHL3) cause a Mendelian disease featuring hypertension hyperkalemia due to constitutive renal salt reabsorption inhibited K + secretion. WNKs modulate activities of aldosterone-regulated electrolyte flux pathways, WNK levels are regulated by CUL3/KLHL3; disease-causing mutations prevent...
Auscultation of heart sounds is a noninvasive and less costly way for congenital disease (CHD) diagnosis, especially pediatric individuals. The deep-learning-based computer-aided sound analysis has been widely studied developed in recent years. In this article, we develop system CHDs diagnosis using two novel lightweight convolution neural networks (CNNs). One key issue most existing systems the scarcity large-scale data sets CNN learning. To end, collect from newborns children with...
Aldosterone-producing adenomas (APAs) are benign tumors of the adrenal gland that constitutively produce salt-retaining steroid hormone aldosterone and cause millions cases severe hypertension worldwide. Either 2 somatic mutations in potassium channel KCNJ5 (G151R L168R, hereafter referred to as KCNJ5MUT) adrenocortical cells account for half APAs These alter selectivity allow abnormal Na+ conductance, resulting membrane depolarization, calcium influx, production, cell proliferation. Because...
Background and Purpose— Hypoxia preconditioning (HPC), rapid or delayed, has been reported to induce neuroprotection against subsequent severe stress. Because δ-opioid receptor (DOR) plays an important role in delayed HPC-induced hypoxic injury, we asked whether DOR is also involved the neuroprotection. Methods— Cultured rat cortical neurons at culture days 8 9 were exposed a short-term hypoxia (1% O 2 for 30 minutes) HPC followed by 30-minute normoxia before exposing glutamate toxicity (100...
Although glucocorticoid (GC)-induced hypertension has commonly been attributed to promiscuous activation of the mineralocorticoid receptor by cortisol, thereby promoting excess reabsorption sodium and water, numerous lines evidence indicate that this is not only or perhaps even primary mechanism. GC induce a number effects on vascular smooth muscle (VSM) <i>in vitro</i> may be pertinent hypertension, but their contribution vivo</i> unknown. To address question, mouse model with...
With-no-lysine kinase 4 (WNK4) regulates electrolyte homeostasis and blood pressure. WNK4 phosphorylates the kinases SPAK (Ste20-related proline alanine-rich kinase) OSR1 (oxidative stress responsive kinase), which then phosphorylate activate renal Na-Cl cotransporter (NCC). levels are regulated by binding to Kelch-like 3, targeting for ubiquitylation degradation. Phosphorylation of 3 PKC or PKA downstream AngII vasopressin signaling, respectively, abrogates binding. We tested whether these...
Portal hypertension is a major contributor to decompensation and death from liver disease, global health problem. Here, we demonstrate homozygous damaging mutations in GIMAP5, small organellar GTPase, four families with unexplained portal hypertension. We show that GIMAP5 expressed hepatic endothelial cells its loss both humans mice results capillarization of sinusoidal (LSECs); this effect also seen when selectively deleted cells. Single-cell RNA-sequencing analysis GIMAP5-deficient mouse...
Abstract To elucidate the pathogenesis of vein Galen malformations (VOGMs), most common and severe congenital brain arteriovenous malformations, we performed an integrated analysis 310 VOGM proband-family exomes 336,326 human cerebrovasculature single-cell transcriptomes. We found Ras suppressor p120 RasGAP ( RASA1 ) harbored a genome-wide significant burden loss-of-function de novo variants (2042.5-fold, p = 4.79 x 10 −7 ). Rare, damaging transmitted were enriched in Ephrin receptor-B4...
The ligand-binding domains of steroid hormone receptors possess a conserved structure with 12 α-helices surrounding central hydrophobic core. On agonist binding, repositioned helix forms pocket 3 (H3) and 5 (H5), where transcriptional coactivators bind. precise molecular interactions responsible for activation these remain to be elucidated. We previously identified H3–H5 interaction that permits progesterone-mediated mutant mineralocorticoid receptor. were intrigued note the potential such...
Significance Primary aldosteronism (increased production of the adrenal steroid hormone aldosterone) is most common cause secondary hypertension. We here generated a mouse model familial hyperaldosteronism type IV with heterozygous gain-of-function mutation in calcium channel gene ( Cacna1h M1560V/+ ). mice have about twofold elevated aldosterone:renin ratios (a screening parameter for primary aldosteronism) and blood pressure, an overall mild phenotype. Elevated aldosterone synthase...
Congenital heart disease (CHD) is a leading cause of infant mortality. We analyzed de novo mutations (DNMs) and very rare transmitted/unphased damaging variants in 248 prespecified genes 11,555 CHD probands. The results identified 60 with significant burden heterozygous variants. Variants these accounted for 10.1% probands similar contributions from transmitted parent–offspring trios that showed incomplete penetrance. DNMs 58% the signal DNMs. Thirty-three were linked to single subtype while...