Involvement of Na,K-pump in SEPYLRFamide-mediated reduction of cholinosensitivity in Helix neurons

Beego is a traditional Chinese complete water-only fasting practice initially developed for spiritual purposes, later extending to physical fitness purposes. Beego notably includes a psychological induction component that includes meditation and abdominal breathing, light body exercise and ends with a specific gradual refeeding program before returning to a normal diet. Beego has regained its popularity in recent decades in China as a strategy for helping people in subhealthy conditions or with metabolic syndrome, but we are unaware of any studies examining the biological effects of this practice. To address this, we here performed a longitudinal study of beego comprising fasting (7 and 14 day cohorts) and a 7-day programmed refeeding phase. In addition to detecting improvements in cardiovascular physiology and selective reduction of blood pressure in hypertensive subjects, we observed that beego decreased blood triacylglycerol (TG) selectively in TG-high subjects and increased cholesterol in all subjects during fasting; however, the cholesterol levels were normalised after completion of the refeeding program. Strikingly, beego reduced platelet formation, activation, aggregation and degranulation, resulting in an alleviated thrombosis risk, yet maintained haemostasis by sustaining levels of coagulation factors and other haemostatic proteins. Mechanistically, we speculate that downregulation of G6B and MYL9 may influence the observed beego-mediated reduction in platelets. Fundamentally, our study supports that supervised beego reduces thrombosis risk without compromising haemostasis capacity. Moreover, our results support that beego under medical supervision can be implemented as non-invasive intervention for reducing thrombosis risk, and suggest several lines of intriguing inquiry for future studies about this fasting practice (http://www.chictr.org.cn/index.aspx, number, ChiCTR1900027451).

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Impact of Organic Matter on Microbially-Mediated Reduction and Mobilization of Arsenic and Iron in Arsenic(V)-Bearing Ferrihydrite

Environmental Science & Technology ◽

10.1021/acs.est.0c05329 ◽

2020 ◽

Author(s):

Xiaolin Cai ◽

Laurel K. ThomasArrigo ◽

Xu Fang ◽

Sylvain Bouchet ◽

Yanshan Cui ◽

...

Keyword(s):

Organic Matter ◽

Mediated Reduction

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Autophagy-mediated reduction of miR-345 contributes to hepatic cystogenesis in polycystic liver disease

JHEP Reports ◽

10.1016/j.jhepr.2021.100345 ◽

2021 ◽

pp. 100345

Author(s):

Tatyana Masyuk ◽

Anatoliy Masyuk ◽

Christy Trussoni ◽

Brynn Howard ◽

Jingyi (Francess) Ding ◽

...

Keyword(s):

Liver Disease ◽

Polycystic Liver Disease ◽

Polycystic Liver ◽

Mediated Reduction

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Crystal structure of steroid reductase SRD5A reveals conserved steroid reduction mechanism

Nature Communications ◽

10.1038/s41467-020-20675-2 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Yufei Han ◽

Qian Zhuang ◽

Bo Sun ◽

Wenping Lv ◽

Sheng Wang ◽

...

Keyword(s):

Crystal Structure ◽

Biochemical Characterization ◽

Substrate Binding ◽

Binding Pocket ◽

Substrate Binding Pocket ◽

Transmembrane Segments ◽

Therapeutic Molecules ◽

Binding Cavity ◽

Immune System Regulation ◽

Mediated Reduction

AbstractSteroid hormones are essential in stress response, immune system regulation, and reproduction in mammals. Steroids with 3-oxo-Δ4 structure, such as testosterone or progesterone, are catalyzed by steroid 5α-reductases (SRD5As) to generate their corresponding 3-oxo-5α steroids, which are essential for multiple physiological and pathological processes. SRD5A2 is already a target of clinically relevant drugs. However, the detailed mechanism of SRD5A-mediated reduction remains elusive. Here we report the crystal structure of PbSRD5A from Proteobacteria bacterium, a homolog of both SRD5A1 and SRD5A2, in complex with the cofactor NADPH at 2.0 Å resolution. PbSRD5A exists as a monomer comprised of seven transmembrane segments (TMs). The TM1-4 enclose a hydrophobic substrate binding cavity, whereas TM5-7 coordinate cofactor NADPH through extensive hydrogen bonds network. Homology-based structural models of HsSRD5A1 and -2, together with biochemical characterization, define the substrate binding pocket of SRD5As, explain the properties of disease-related mutants and provide an important framework for further understanding of the mechanism of NADPH mediated steroids 3-oxo-Δ4 reduction. Based on these analyses, the design of therapeutic molecules targeting SRD5As with improved specificity and therapeutic efficacy would be possible.

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Central glucagon-like peptide 1 receptor-induced anorexia requires glucose metabolism-mediated suppression of AMPK and is impaired by central fructose

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00446.2012 ◽

2013 ◽

Vol 304 (7) ◽

pp. E677-E685 ◽

Cited By ~ 34

Author(s):

Melissa A. Burmeister ◽

Jennifer Ayala ◽

Daniel J. Drucker ◽

Julio E. Ayala

Keyword(s):

Food Intake ◽

Glucose Metabolism ◽

Dependent Manner ◽

Anorectic Effect ◽

Dependent Inhibition ◽

Glycolytic Inhibitor ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1 ◽

Amp Activated Protein Kinase ◽

Mediated Reduction

Glucagon-like peptide-1 (GLP-1) suppresses food intake via activation of a central (i.e., brain) GLP-1 receptor (GLP-1R). Central AMP-activated protein kinase (AMPK) is a nutrient-sensitive regulator of food intake that is inhibited by anorectic signals. The anorectic effect elicited by hindbrain GLP-1R activation is attenuated by the AMPK stimulator AICAR. This suggests that central GLP-1R activation suppresses food intake via inhibition of central AMPK. The present studies examined the mechanism(s) by which central GLP-1R activation inhibits AMPK. Supporting previous findings, AICAR attenuated the anorectic effect elicited by intracerebroventricular (icv) administration of the GLP-1R agonist exendin-4 (Ex-4). We demonstrate that Ex-4 stimulates glycolysis and suppresses AMPK phosphorylation in a glucose-dependent manner in hypothalamic GT1-7 cells. This suggests that inhibition of AMPK and food intake by Ex-4 requires central glucose metabolism. Supporting this, the glycolytic inhibitor 2-deoxyglucose (2-DG) attenuated the anorectic effect of Ex-4. However, icv glucose did not enhance the suppression of food intake by Ex-4. AICAR had no effect on Ex-4-mediated reduction in locomotor activity. We also tested whether other carbohydrates affect the anorectic response to Ex-4. Intracerebroventricular pretreatment with the sucrose metabolite fructose, an AMPK activator, attenuated the anorectic effect of Ex-4. This potentially explains the increased food intake observed in sucrose-fed mice. In summary, we propose a model whereby activation of the central GLP-1R reduces food intake via glucose metabolism-dependent inhibition of central AMPK. We also suggest that fructose stimulates food intake by impairing central GLP-1R action. This has significant implications given the correlation between sugar consumption and obesity.

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