Mitochondrial fatty acid oxidation regulates adult muscle stem cell function through modulating metabolic flux and protein acetylation.

During homeostasis and regeneration, satellite cells, the resident stem cells of skeletal muscle, have distinct metabolic requirements for fate transitions between quiescence, proliferation and differentiation. However, the contribution of distinct energy sources to satellite cell metabolism and function remains largely unexplored. Here, we uncover a role of mitochondrial fatty acid oxidation (FAO) in satellite cell integrity and function.

Gly-β-MCA is a potent anti-cholestasis agent against "human-like" hydrophobic bile acid-induced biliary injury in mice.

Cholestasis is a chronic liver disease with limited therapeutic options. Hydrophobic bile acid-induced hepatobiliary injury is a major pathological driver of cholestasis progression. This study investigates the anti-cholestasis efficacy and mechanisms of action of glycine-conjugated β-muricholic acid (Gly-β-MCA).

Cullin 3 RING E3 ligase inactivation causes NRF2-dependent NADH reductive stress, hepatic lipodystrophy, and systemic insulin resistance.

Cullin RING E3 ligases (CRL) have emerged as key regulators of disease-modifying pathways and therapeutic targets. Cullin3 (Cul3)-containing CRL (CRL3) has been implicated in regulating hepatic insulin and oxidative stress signaling. However, CRL3 function in liver pathophysiology is poorly defined.

Deletion of hepatocyte cysteine dioxygenase type 1, a bile acid repressed gene, enhances glutathione synthesis and ameliorates acetaminophen hepatotoxicity.

Liver is a major organ that metabolizes sulfur amino acids cysteine, which is the substrate for the synthesis of many essential cellular molecules including GSH, taurine, and coenzyme A. Bile acid-activated farnesoid x receptor (FXR) inhibits cysteine dioxygenase type 1 (CDO1), which mediates hepatic cysteine catabolism and taurine synthesis. To define the impact of bile acid inhibition of CDO1 on hepatic sulfur amino acid metabolism and antioxidant capacity, we developed hepatocyte-specific CDO1 knockout mice (Hep-CDO1 KO) and hepatocyte specific CDO1 transgenic mice (Hep-CDO1 Tg).

Glycine-β-Muricholic Acid Improves Liver Fibrosis and Gut Barrier Function by Reducing Bile Acid Pool Size and Hydrophobicity in Male Knockout Mice.

knockout mice lack the enzyme that produces muricholic acids and show a "human-like" hydrophobic bile acid pool-induced hepatobiliary injury. In this study, we investigated the potential anti-cholestasis effect of glycine-conjugated β muricholic acid (G-β-MCA) in male KO mice based on its hydrophilic physiochemical property and signaling property as an farnesoid X receptor (FXR) antagonist. Our results showed that G-β-MCA treatment for 5 weeks alleviated ductular reaction and liver fibrosis and improved gut barrier function.

Association of serum thymosin β4 with malnutrition-inflammation-atherosclerosis syndrome in peritoneal dialysis patients: a cross-sectional study.

Background: Malnutrition-inflammation-atherosclerosis (MIA) syndrome may worsen the prognosis of peritoneal dialysis (PD) patients. Serum thymosin β4 (sTβ4) protects against inflammation, fibrosis and cardiac dysfunction.

Objectives: The present study aimed to characterize the association between sTβ4 and MIA syndrome as well as to investigate the potential of regulating sTβ4 to improve the prognosis of PD patients.

Impact of the degree of worsening renal function and B-type natriuretic peptide on the prognosis of patients with acute heart failure.

Background: The impact of the degree of worsening renal function (WRF) and B-type natriuretic peptide (BNP) on the prognosis of patients with acute heart failure (AHF) is still debatable. The present study investigated the influence of different degrees of WRF and BNP levels at discharge on 1-year all-cause mortality in AHF.

Methods: Hospitalized AHF patients diagnosed with acute new-onset/worsening of chronic heart failure (HF) between January 2015 and December 2019 were included in this study.

Combining ASBT inhibitor and FGF15 treatments enhances therapeutic efficacy against cholangiopathy in female but not male Cyp2c70 KO mice.

Therapeutic reduction of hydrophobic bile acids exposure is considered beneficial in cholestasis. The Cyp2c70 KO mice lack hydrophilic muricholic acids and have a human-like hydrophobic bile acid pool resulting in hepatobiliary injury. This study investigates if combining an apical sodium-dependent bile acid transporter inhibitor GSK2330672 (GSK) and fibroblast growth factor-15 (FGF15) overexpression, via simultaneous inhibition of bile acid synthesis and gut bile acid uptake, achieves enhanced therapeutic efficacy in alleviating hepatobiliary injury in Cyp2c70 KO mice.

Baseline anxiety disorders are associated with progression of diabetic kidney disease in type 2 diabetes.

Background: Diabetic kidney disease (DKD) is a leading cause of kidney failure worldwide. Anxiety has been associated with disease progression in non-diabetes patients. We aimed to examine the prospective association between anxiety and progression of DKD in type 2 diabetes.

EZH2 promotes angiogenesis in peritoneal dialysis by epigenetically activating SP4 expression in the IL-6/sIL-6R signalling pathway.

Interleukin-6 (IL-6)/soluble IL-6 receptor (sIL-6R) promotes peritoneal angiogenesis by stimulating SP4-mediated vascular endothelial growth factor (VEGF) production in peritoneal dialysis (PD). Moreover, histone methyltransferase enhancer of zeste homologue 2 (EZH2) is involved in IL-6/sIL-6R signalling via the acceleration of vascular endothelial growth factor (VEGF)-induced angiogenesis. However, the molecular mechanism underlying how EZH2 epigenetically activates VFGF expression in IL-6/sIL-6R signalling during PD is still unclear.

Organophosphine as an Alkyl Transfer Shuttle for the Direct β-Alkylation of Chalcones Using Alkyl Halides.

We report an efficient alkyl transfer strategy for the direct β-alkylation of chalcones using commercially available alkyl bromides as alkyl reagents. In this transformation, the -phosphanyl substituent in the chalcones is crucial for controlling their reactivity and selectivity. It also serves as a reliable alkyl transfer shuttle to transform electrophilic alkyl bromides into nucleophilic alkyl species in the form of quaternary phosphonium salts and transfer the alkyl group effectively to the β-position of the chalcones.

Low protein diet supplemented with ketoacids on muscle wasting in chronic kidney disease: A clinical trial.

Aim: Nutrition is an important part of the care of patients with chronic kidney disease (CKD). However, there is limited clinical research on the skeletal muscle nutrition of patients with CKD. We carried out this study to find out whether a low-protein diet supplemented with ketoacids (LPD + KA) could improve muscle wasting in patients with CKD.

TFEB regulates sulfur amino acid and coenzyme A metabolism to support hepatic metabolic adaptation and redox homeostasis.

Fatty liver is a highly heterogenous condition driven by various pathogenic factors in addition to the severity of steatosis. Protein insufficiency has been causally linked to fatty liver with incompletely defined mechanisms. Here we report that fatty liver is a sulfur amino acid insufficient state that promotes metabolic inflexibility via limiting coenzyme A availability.

Chchd10 is dispensable for myogenesis but critical for adipose browning.

The Chchd10 gene encodes a coiled-coil-helix-coiled-coil-helix-domain containing protein predicted to function in the mitochondrion and nucleus. Mutations of Chchd10 are associated with ALS, dementia and myopathy in humans and animal models, but how knockout of Chchd10 (Chchd10) affects various tissues especially skeletal muscle and adipose tissues remains unclear. Here we show that Chchd10 expression increases as myoblasts and preadipocytes differentiate.

Dearomative Periphery Modification of Quinolinium Salts to Assemble Ring-Encumbered Pyrrolidine-Tetrahydroquinoline Polycycles.

We report an unexpected dearomative periphery modification strategy for transforming quinolinium salts into structurally crowded pyrrolidine-tetrahydroquinoline polycyclic systems with complete regio- and diastereoselectivity. Importantly, the reaction pathway was regulated by simply tuning the substituents, achieving substituent-directed divergent synthesis. The notable features of this transformation include readily available starting materials, green conditions, a simple workup procedure, high bond- and ring-forming efficiency, and substituent-directed diverse synthesis.

Cullin neddylation inhibitor attenuates hyperglycemia by enhancing hepatic insulin signaling through insulin receptor substrate stabilization.

Hepatic insulin resistance is a hallmark feature of nonalcoholic fatty liver disease and type-2 diabetes and significantly contributes to systemic insulin resistance. Abnormal activation of nutrient and stress-sensing kinases leads to serine/threonine phosphorylation of insulin receptor substrate (IRS) and subsequent IRS proteasome degradation, which is a key underlying cause of hepatic insulin resistance. Recently, members of the cullin-RING E3 ligases (CRLs) have emerged as mediators of IRS protein turnover, but the pathophysiological roles and therapeutic implications of this cellular signaling regulation is largely unknown.

TLR13 contributes to skeletal muscle atrophy by increasing insulin resistance in chronic kidney disease.

Objectives: Insulin resistance in chronic kidney disease (CKD) stimulates muscle wasting, but the molecular processes behind the resistance are undetermined. However, inflammation in skeletal muscle is implicated in the pathogenesis of insulin resistance and cachexia. Toll-like receptors (TLRs) are known to regulate local innate immune responses, and microarray data have shown that Tlr13 is upregulated in the muscles of mice with CKD, but the relevance is unknown.

Lipid droplet dynamics regulate adult muscle stem cell fate.

The lipid droplet (LD) is a central hub for fatty acid metabolism in cells. Here we define the dynamics and explore the role of LDs in skeletal muscle satellite cells (SCs), a stem cell population responsible for muscle regeneration. In newly divided SCs, LDs are unequally distributed in sister cells exhibiting asymmetric cell fates, as the LD cell self-renews while the LD cell commits to differentiation.

Skeletal remodeling of chalcone-based pyridinium salts to access isoindoline polycycles and their bridged derivatives.

Simultaneous deconstructive ring-opening and skeletal reconstruction of an inert, aromatic pyridinium ring is of great importance in synthetic communities. However, research in this area is still in its infancy. Here, a skeletal re-modeling strategy was developed to transform chalcone-based pyridinium salts into structurally intriguing polycyclic isoindolines through a dearomative ring-opening/ring-closing sequence.

Thalidomide Suppresses Angiogenesis Through the Signal Transducer and Activator of Transcription 3/SP4 Signaling Pathway in the Peritoneal Membrane.

Peritoneal angiogenesis is the key pathophysiological factor that limits peritoneal ultrafiltration during peritoneal dialysis (PD) in uremic patients. Thalidomide has been confirmed to inhibit angiogenesis by inhibiting the secretion of vascular endothelial growth factor (VEGF), but the exact mechanism by which thalidomide inhibits vascular proliferation during PD is still unclear. Here, the objective of the present study was to investigate whether the reduction in VEGF production by human peritoneal mesothelial cells (HPMCs) was controlled by thalidomide.