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Total 445 results found since Jan 2013.

Salt causes aging-associated hypertension via vascular Wnt5a under Klotho deficiency
Aging is associated with a high prevalence of hypertension due to elevated susceptibility of BP to dietary salt, but its mechanism is unknown. Serum levels of Klotho, an anti-aging factor, decline with age. We found that high salt (HS) increased BP in aged mice and young heterozygous Klotho-knockout mice and was associated with increased vascular expression of Wnt5a and p-MYPT1, which indicate RhoA activity. Not only the Wnt inhibitor LGK974 and the Wnt5a antagonist Box5 but Klotho supplementation inhibits HS-induced BP elevation, similarly to the Rho kinase inhibitor fasudil, associated with reduced p-MYPT1 expression in ...
Source: Journal of Clinical Investigation - June 29, 2020 Category: Biomedical Science Authors: Wakako Kawarazaki, Risuke Mizuno, Mitsuhiro Nishimoto, Nobuhiro Ayuzawa, Daigoro Hirohama, Kohei Ueda, Fumiko Kawakami-Mori, Shigeyoshi Oba, Takeshi Marumo, Toshiro Fujita Source Type: research

Genes, Vol. 11, Pages 720: Cardiac Transcriptome Analysis Reveals Nr4a1 Mediated Glucose Metabolism Dysregulation in Response to High-Fat Diet
ng Xia Chen Obesity is associated with an increased risk of developing cardiovascular disease (CVD), with limited alterations in cardiac genomic characteristics known. Cardiac transcriptome analysis was conducted to profile gene signatures in high-fat diet (HFD)-induced obese mice. A total of 184 differentially expressed genes (DEGs) were identified between groups. Based on the gene ontology (GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of DEGs, the critical role of closely interlocked glucose metabolism was determined in HFD-induced cardiac remodeling DEGs, inclu...
Source: Genes - June 28, 2020 Category: Genetics & Stem Cells Authors: Lihui Men Wenting Hui Xin Guan Tongtong Song Xuan Wang Siwei Zhang Xia Chen Tags: Article Source Type: research

Macrophage Sphingosine 1-Phosphate Receptor 2 Blockade Attenuates Liver Inflammation and Fibrogenesis Triggered by NLRP3 Inflammasome
NLR family pyrin domain containing 3 (NLRP3) inflammasome accompanies chronic liver injury and is a critical mediator of inflammation-driven liver fibrosis. Sphingosine 1-phosphate (S1P)/S1P Receptor (S1PR) signaling participates in liver fibrogenesis by affecting bone marrow (BM)-derived monocytes/macrophage (BMM) activation. However, the relationship between S1P/S1PR signaling and NLRP3 inflammasome in BMMs remains unclear. Here, we found significantly elevated gene expression of NLRP3 inflammasome components (NLRP3, pro-interleukin-1β, and pro-interleukin-18) and the activation of NLRP3 inflammasome significantly eleva...
Source: Frontiers in Immunology - June 25, 2020 Category: Allergy & Immunology Source Type: research

Intermittent fasting promotes adult hippocampal neuronal differentiation by activating GSK ‐3β in 3xTg‐AD mice
AbstractModerate dietary restriction can ameliorate age ‐related chronic diseases such as Alzheimer's disease (AD) by increasing the expression of neurotrophic factors and promoting neurogenesis in the brain. Glycogen synthase kinase‐3β (GSK‐3β) signaling is essential for the coordination of progenitor cell proliferation and differentiation durin g brain development. The mechanisms by which GSK‐3β is involved in dietary restriction induced neurogenesis and cognitive improvement remain unclear. Six‐month‐old male 3xTg‐AD and wild type mice were fed on alternate days (intermittent fasting, IF) or ad libitum ...
Source: Journal of Neurochemistry - June 22, 2020 Category: Neuroscience Authors: Wei Li, Meijian Wu, Yilin Zhang, Xuemin Wei, Jiankun Zang, Yinghua Liu, Yanping Wang, Cheng ‐Xin Gong, Wei Wei Tags: ORIGINAL ARTICLE Source Type: research

Naringenin Upregulates AMPK-Mediated Autophagy to Rescue Neuronal Cells From β-Amyloid (1–42) Evoked Neurotoxicity
AbstractDeposition of an amyloid- β peptide is one of the first events in the pathophysiology of Alzheimer’s disease (AD) and is clinically characterized by Aβ plaques, tau tangles, and behavioral impairments that lead to neuronal death. A substantial number of studies encourage targeting the skewness in the production and degra dation of amyloid-β could be among the promising therapies in the disease. Neuronal autophagy has emerged for an essential role in the degradation of such toxic aggregate-prone proteins in various neurodegenerative diseases. We profiled a small library of common dietary compounds and identifie...
Source: Molecular Neurobiology - June 15, 2020 Category: Neurology Source Type: research

Vitamin D reduces autophagy by regulating NF- κB resistance to Aspergillus fumigatus infection.
CONCLUSIONS: Vitamin D deficiency can aggravate the inflammatory damage in the lungs of Aspergillus fumigatus. When the body is sufficient in vitamin D, if the lungs infect Aspergillus fumigatus spores, the body may resist the infection of Aspergillus fumigatus by reducing the expression of NF-κB, inflammatory factors and autophagy. PMID: 32485309 [PubMed - as supplied by publisher]
Source: Gene - May 29, 2020 Category: Genetics & Stem Cells Authors: Hu S, Dai J, Chen X Tags: Gene Source Type: research

14-3-3 gamma, a novel regulator of the large-conductance Ca2+-activated K+ channels.
Abstract 14-3-3 gamma (γ) is a small protein regulating the target proteins through binding to the phosphorylated serine/threonine residues. Sequence analysis of large-conductance Ca2+-activated K+ (BK) channel revealed a putative 14-3-3 binding site in the C-terminal region. Our previous data showed that 14-3-3γ is widely expressed in the mouse kidney. We, therefore, hypothesized that 14-3-3γ has a novel role in the regulation of BK channel activity and protein expression. We first demonstrated the interaction of 14-3-3γ with BKα by co-immunoprecipitation. In HEK293 cells stably expressing BKα (HEK BKα cel...
Source: American Journal of Physiology. Renal Physiology - May 27, 2020 Category: Physiology Authors: Chen S, Feng X, Chen X, Zhuang Z, Xiao J, Fu H, Klein JD, Wang XH, Hoover RS, Eaton DC, Cai H Tags: Am J Physiol Renal Physiol Source Type: research

Knockout of the Circadian Clock Protein PER1 Results in Sex-Dependent Alterations of ET-1 Production in Mice in Response to a High Salt Diet plus Mineralocorticoid Treatment.
Abstract Previously, we showed that global knockout (KO) of the circadian clock transcription factor PER1 in male, but not female, mice fed a high salt diet plus mineralocorticoid treatment (HS/DOCP) resulted in non-dipping hypertension and decreased night/day ratio of sodium (Na) excretion. Additionally, we have shown that the endothelin-1 (ET-1) gene is targeted by both PER1 and aldosterone. We hypothesized that ET-1 would exhibit a sex-specific response to HS/DOCP treatment in PER1 KO. Here we show that male, but not female, global PER1 KO mice exhibit a decreased night/day ratio of urinary ET-1. Gene expressio...
Source: Canadian Journal of Physiology and Pharmacology - May 20, 2020 Category: Drugs & Pharmacology Authors: Douma LG, Crislip GR, Cheng KY, Barral D, Masten S, Holzworth MR, Roig E, Glasford K, Beguiristain K, Li W, Bratanatawira P, Lynch IJ, Cain BD, Wingo CS, Gumz ML Tags: Can J Physiol Pharmacol Source Type: research

Folic acid attenuates high-fat diet-induced steatohepatitis via deacetylase SIRT1-dependent restoration of PPAR α.
CONCLUSION: Folic acid improves hepatic lipid metabolism by upregulating PPARα levels via a SIRT1-dependent mechanism and restores hepatic one-carbon metabolism and diversity of gut microbiota, thereby attenuating HFD-induced NASH in rats. PMID: 32476787 [PubMed - in process]
Source: World Journal of Gastroenterology : WJG - May 13, 2020 Category: Gastroenterology Authors: Xin FZ, Zhao ZH, Zhang RN, Pan Q, Gong ZZ, Sun C, Fan JG Tags: World J Gastroenterol Source Type: research

Gut-Derived Serotonin Contributes to the Progression of Non-Alcoholic Steatohepatitis via the Liver HTR2A/PPAR γ2 Pathway
The precipitous increase in occurrence of non-alcoholic steatohepatitis (NASH) is a serious threat to public health worldwide. The pathogenesis of NASH has not yet been thoroughly studied. We aimed to elucidate the interplay between serotonin (5-hydroxytryptamine, 5-HT) and NASH. The serum 5-HT levels in patients with non-alcoholic fatty liver disease (NAFLD) and a rat fed with high fat-sucrose diet (HFSD) were evaluated using liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-QTOF MS)/MS. The peripheral Tph1 inhibitor, LP533401, and a tryptophan (TRP)-free diet were administered to rats with NASH...
Source: Frontiers in Pharmacology - May 13, 2020 Category: Drugs & Pharmacology Source Type: research

Icariin Improves Age-Related Testicular Dysfunction by Alleviating Sertoli Cell Injury via Upregulation of the ER α/Nrf2-Signaling Pathway
Sertoli cells play crucial roles in spermatogenesis and are impaired by aging. Icariin, a flavonoid from Epimedium, has been reported to exhibit anti-aging effects and improve testicular dysfunction in the clinical setting. However, whether icariin improves age-related degeneration of testicular function via protection from Sertoli cell injury remains unclear. In the present study, we evaluated the protective effect of icariin on Sertoli cell injury and explored the possible mechanism(s) in vivo and in vitro. Dietary administration of icariin for 4 months significantly ameliorated the age-related decline in testicular func...
Source: Frontiers in Pharmacology - May 11, 2020 Category: Drugs & Pharmacology Source Type: research

Mechanisms of impaired pancreatic β‑cell function in high‑fat diet‑induced obese mice: The role of endoplasmic reticulum stress.
Authors: Yi X, Cai X, Wang S, Xiao Y Abstract The aim of the study was to examine whether there was excessive endoplasmic reticulum stress (ERs) in the islets of high‑fat diet (HFD)‑induced obese mice, as well as the effects of ERs on β‑cell function. Male C57BL/6J mice were fed a HFD for 16 weeks. Pancreatic β‑cell function was evaluated using intraperitoneal glucose tolerance and insulin release tests, and via electron microscopy. The expression of activating transcription factor 6 (ATF6) and phosphorylated (p)‑eukaryotic initiation factor 2α (eIF2α) were detected via immunofluorescence staining to...
Source: Molecular Medicine Reports - April 25, 2020 Category: Molecular Biology Tags: Mol Med Rep Source Type: research

Chemerin/CMKLR1 Axis Promotes Inflammation and Pyroptosis by Activating NLRP3 Inflammasome in Diabetic Cardiomyopathy Rat
In this study, we investigated the role of the chemerin/CMKLR1 axis in mediating inflammation and cell death in DCM. Sprague–Dawley rats, treated with a high-fat diet and low-dose of streptozotocin, were used as a DCM model. CMKLR1 expression was knocked down by siRNA (CMKLR1-siRNA) to evaluate the role of CMKLR1 in DCM. Chemerin-treated H9c2 cells were used to investigate the factors acting downstream of the chemerin/CMKLR1 axis. LDH release and EthD-III staining were used to measure the ratio of cell death in vitro. CMKLR1-siRNA and siRNA against nucleotide-binding oligomerization domain-like receptors 3 (NLRP3-siRNA) ...
Source: Frontiers in Physiology - April 22, 2020 Category: Physiology Source Type: research

Myeloid-specific Asxl2 deletion limits diet-induced obesity by regulating energy expenditure
We previously established that global deletion of the enhancer of trithorax and polycomb (ETP) gene, Asxl2, prevents weight gain. Because proinflammatory macrophages recruited to adipose tissue are central to the metabolic complications of obesity, we explored the role of ASXL2 in myeloid lineage cells. Unexpectedly, mice without Asxl2 only in myeloid cells (Asxl2ΔLysM) were completely resistant to diet-induced weight gain and metabolically normal despite increased food intake, comparable activity, and equivalent fecal fat. Asxl2ΔLysM mice resisted HFD-induced adipose tissue macrophage infiltration and inflammatory cytok...
Source: Journal of Clinical Investigation - April 21, 2020 Category: Biomedical Science Authors: Wei Zou, Nidhi Rohatgi, Jonathan R. Brestoff, John R. Moley, Yongjia Li, Jesse W. Williams, Yael Alippe, Hua Pan, Terri A. Pietka, Gabriel Mbalaviele, Elizabeth P. Newberry, Nicholas O. Davidson, Anwesha Dey, Kooresh I. Shoghi, Richard D. Head, Samuel A. Source Type: research

FGF21 induces autophagy-mediated cholesterol efflux to inhibit atherogenesis via RACK1 up-regulation.
In this study, ApoE-/- mice were fed a high-fat diet (HFD) with or without FGF21 and FGF21 + 3-Methyladenine (3MA) for 12 weeks. Our results showed that FGF21 inhibited AS in HFD-fed ApoE-/- mice, which was reversed by 3MA treatment. Moreover, FGF21 increased plaque RACK1 and autophagy-related protein (LC3 and beclin-1) expression in ApoE-/- mice, thus preventing AS. However, these proteins were inhibited by LV-RACK1 shRNA injection. Foam cell development is a crucial determinant of AS, and cholesterol efflux from foam cells represents an important defensive measure of AS. In this study, foam cells were treated with FGF...
Source: J Cell Mol Med - March 29, 2020 Category: Molecular Biology Authors: Xiaolong L, Dongmin G, Liu M, Zuo W, Huijun H, Qiufen T, XueMei H, Wensheng L, Yuping P, Jun L, Zhaolin Z Tags: J Cell Mol Med Source Type: research