Dihydromyricetin ameliorates hepatic steatosis and insulin resistance via AMPK/PGC-1α and PPARα-mediated autophagy pathway.

BACKGROUND: Dihydromyricetin (DHM), a flavonoid compound of natural origin, has been identified in high concentrations in ampelopsis grossedentata and has a broad spectrum of biological and pharmacological functions, particularly in regulating glucose and lipid metabolism. The objective of this research was to examine how DHM affected nonalcoholic fatty liver disease (NAFLD) and its underlying mechanisms involved in the progression of NAFLD in a rat model subjected to a high-fat diet (HFD). Additionally, the study examines the underlying mechanisms in a cellular model of steatohepatitis using palmitic acid (PA)-treated HepG2 cells, with a focus on the potential correlation between autophagy and hepatic insulin resistance (IR) in the progress of NAFLD. METHODS: SD rats were exposed to a HFD for a period of eight weeks, followed by a treatment with DHM (at doses of 50, 100, and 200 mg·kg-1·d-1) for additional six weeks. The HepG2 cells received a 0.5 mM PA treatment for 24 h, either alone or in conjunction with DHM (10 µM). The histopathological alterations were assessed by the use of Hematoxylin-eosin (H&E) staining. The quantification of glycogen content and lipid buildup in the liver was conducted by the use of PAS and Oil Red O staining techniques. Serum lipid and liver enzyme levels were also measured. Autophagic vesicle and autolysosome morphology was studied using electron microscopy. RT-qPCR and/or western blotting techniques were used to measure IR- and autophagy-related factors levels. RESULTS: The administration of DHM demonstrated efficacy in ameliorating hepatic steatosis, as seen in both in vivo and in vitro experimental models. Moreover, DHM administration significantly increased GLUT2 expression, decreased G6Pase and PEPCK expression, and improved IR in the hepatic tissue of rats fed a HFD and in cells exhibiting steatosis. DHM treatment elevated Beclin 1, ATG 5, and LC3-II levels in hepatic steatosis models, correlating with autolysosome formation. The expression of AMPK levels and its downstream target PGC-1α, and PPARα were decreased in HFD-fed rats and PA-treated hepatocytes, which were reversed through DHM treatment. AMPK/ PGC-1α and PPARα knockdown reduced the impact of DHM on hepatic autophagy, IR and accumulation of hepatic lipid. CONCLUSIONS: Our findings revealed that AMPK/ PGC-1α, PPARα-dependent autophagy pathways in the pathophysiology of IR and hepatic steatosis has been shown, suggesting that DHM might potentially serve as a promising treatment option for addressing this disease.

Cross-Talk Between Thyroid Disorders and Nonalcoholic Fatty Liver Disease: From Pathophysiology to Therapeutics.

The medical community acknowledges the presence of thyroid disorders and nonalcoholic fatty liver disease (NAFLD). Nevertheless, the interconnection between these two circumstances is complex. Thyroid hormones (THs), including triiodothyronine (T3) and thyroxine (T4), and thyroid-stimulating hormone (TSH), are essential for maintaining metabolic balance and controlling the metabolism of lipids and carbohydrates. The therapeutic potential of THs, especially those that target the TRß receptor isoform, is generating increasing interest. The review explores the pathophysiology of these disorders, specifically examining the impact of THs on the metabolism of lipids in the liver. The purpose of this review is to offer a thorough analysis of the correlation between thyroid disorders and NAFLD, as well as suggest potential therapeutic approaches for the future.

Prmt4-mediated methylation of NF-κB is critical for neural differentiation of embryonic stem cells.

Neural differentiation is a complex process regulated by multiple signaling at different regulatory levels. Though great progresses have been made in understanding the mechanisms of neural differentiation, post-translational regulation of neural differentiation remains largely unknown. In this study, we found Prmt4, one of the methyltransferases catalyzing protein arginine methylation, is highly expressed in neural stem cells (NSCs) and associated with neural differentiation. Knockout of Prmt4 in mESCs blocked neural differentiation by inhibiting NF-κB activation. Mechanistically, Prmt4 interacts with NF-κB component p65 to promote its methylation, resulting in increased activation of NF-κB signaling during neural differentiation. Our study not only identified Prmt4 as novel regulator of neural differentiation, but also highlighted the importance of protein arginine methylation in cell fate transition.

Selenium-induced anion vacancy and active site migration stimulating remarkable sulfide Na-Ion storage.

Heterojunctions and controllable anionic vacancies are perceived to be powerful means of ameliorating the performance of sodium-ion batteries assignable to their unique physical and chemical properties. However, the mechanism by which heterojunction and vacancy structures affect sodium-ion battery storage remains to be systemically explored. In this study, the Se doped CoS2@CoS1.035@Carbon (Se-CoS2@CoS1.035@C) heterostructure with anion vacancy was synthesized by a one-step calcination. These heterostructures with lower metal oxidation states and anionic vacancies exhibit exceptional Na+ storage performance (554.3 mA h g-1 after 1500 cycles at 5.0 A g-1). Both electrochemical tests and theoretical calculations demonstrate excellent pseudocapacitive behavior and enhanced Na+ adsorption during discharge because of anionic vacancies and Se doping. Additionally, introducing weaker Co-Se bonds and extending Co-S and Co-Se bonds reduce binding energies, which effectively accelerates the conversion reaction. Our findings provide a feasible way to rationally design and facilely prepare heterostructured anode materials with rich anionic vacancies for sodium-ion batteries.

In-situ growth of carbon nanotubes for the modification of wood-derived biomass porous carbon to achieve efficient Low/Mid-Frequency electromagnetic wave absorption.

Ideal wave-absorbing materials are required to possess the characteristics such as being "broad, lightweight, thin, and strong." Biomass-derived materials for absorbing electromagnetic waves (EMWs) are widely explored due to their low cost, lightweight, environmentally friendly, high specific surface area, and porous structure. In this study, wood was used as the raw material, and N-doped carbon nanotubes were grown in situ in porous carbon derived from wood, loaded with magnetic metal Co nanoparticles through chemical vapor deposition. The Fir@Co@CNT composite material exhibited a three-dimensional conductive electromagnetic network structure and excellent impedance matching, thereby demonstrating excellent wave absorption performance. By controlling the introduction of carbon nanotubes, the roles of polarization loss and conduction loss in the Fir@Co@CNT composite material were precisely regulated. The Fir@Co@CNT 1:5 composite material achieved a minimum reflection loss (RLmin) of -43.03 dB in the low-frequency region and a maximum effective absorption bandwidth (EABmax) of 4.3 GHz (1.5 mm). Meanwhile, the Fir@Co@CNT 1:10 composite material achieved a RLmin of -52 dB with a thickness of only 2.3 mm, along with an EABmax of 4.2 GHz (1.6 mm). Both materials collectively cover the entire C-band, X-band, and Ku-band in terms of EAB. This work introduces a method for regulating polarization loss and conduction loss, showcasing the potential of biomass carbon materials as low-frequency EMW absorption materials for the first time. It also provides a new direction for the development and application of environmentally friendly, lightweight, high-performance wave-absorbing materials.

Tuning Electromagnetic Parameters Induced by Synergistic Dual-Polarization Enhancement Mechanisms with Amorphous Cobalt Phosphide with Phosphorus Vacancies for Excellent Electromagnetic Wave Dissipation Performance.

The understanding of amorphous and heterojunction materials has been widely used in the field of electromagnetic wave absorption due to their unique physical and chemical properties. However, the effectiveness of individual strategies currently used is still limited. Well-designed compositions and amorphous structures simplify the effect of different polarization mechanisms on the absorption of electromagnetic waves. In this work, through the carbonization and controlled phosphating of one-dimensional Co Metal-Organic Framework (Co-MOF) nanorods, the synthesis of complex components and amorphous CoPx with phosphorus vacancies is successfully accomplished, thus adjusting the optimization of electromagnetic parameters. Phosphorus-vacancy-induced defective polarization loss and enhanced-electronegativity-differences-induced dipole polarization loss synergistically as a dual-polarization strategy significantly improved the electromagnetic parameters and impedance matching. In conclusion, the electromagnetic parameters of the Co@CoPx@C composites are indeed significantly regulated, with reflection losses of -55 dB and a bandwidth of up to 5.5 GHz. These innovative research ideas provide instructive thinking for the development of amorphous absorbers with vacancies.

The efficacy and safety of probiotics in patients with irritable bowel syndrome: Evidence based on 35 randomized controlled trials.

BACKGROUND & OBJECTIVES: Irritable bowel syndrome (IBS) is a functional bowel disorder that may involve disturbance of the gastrointestinal microbiota. We performed a systematic review and meta-analysis of the efficacy and safety of probiotics in patients with IBS. METHODS: We searched the Cochrane Library, PubMed, EMBASE and Web of Science databases up to 1 April, 2019. Randomized controlled trials (RCTs) involving adults with IBS that compared probiotics to placebo or no therapy were eligible for the analysis. Dichotomous symptom data were pooled to calculate the relative risk (RR) with a 95% confidence interval (CI) of remaining symptoms after therapy. Continuous data were pooled using a standardized mean difference (SMD) with the 95% CI. Two reviewers assessed trial quality and extracted data independently. RESULTS: Thirty-five RCTs involving 3,452 patients were included in the analysis. Compared with placebo, patients using probiotics had a lower incidence of persistence of symptoms (RR 0.79, 95% CI 0.70 to 0.89, P < 0.0001). Also, probiotics exerted a beneficial effect on global symptoms and the abdominal pain score (SMD -0.25, 95% CI -0.36 to -0.14, P < 0.00001), bloating score (SMD -0.15, 95% CI -0.27 to -0.03, P = 0.01), and flatulence score (SMD -0.20, 95% CI -0.35 to -0.05, P = 0.01). However, patients treated with probiotics had a higher incidence of any adverse event (RR 1.21; 95% CI 1.02 to 1.44). CONCLUSIONS: Supplementation with multi-strain probiotics can improve IBS symptoms. Further research is required if probiotics are to be adopted as a treatment for IBS.

Novel Oxovanadium Complex VO(hntdtsc)(NPIP): Anticancer Activity and Mechanism of Action on HeLa Cells.

Oxovanadium complexes, particularly vanadyl (IV) derivatives with hybrid ligands of Schiff base and polypyridyl, have been demonstrated to possess great anticancerous therapeutic efficacy. However, most of the studies on the activity of these oxovanadium complexes have mainly focused on in vitro studies, and animal studies in vivo are extremely scarce. Based on the antitumor test results of four novel oxovanadium complexes in our previous work, this work further conducted a comprehensive antitumor activity study in vitro and in vivo on VO(hntdtsc)(NPIP), which owned the strongest inhibitory activity in vitro on multiple tumor cell proliferation. The cellular mechanism study suggested that VO(hntdtsc)(NPIP) inhibited the cell proliferation via arresting the cell cycle at G0/G1 phase through the p16-cyclin D1-CDK4-p-Rb pathway and inducing cell apoptosis through mitochondrial-dependent apoptosis pathway on HeLa cells. Inconsistent with the effects in vitro, VO(hntdtsc)(NPIP) significantly inhibited the growth of tumor and induced the apoptosis of cancer cells in mice xenograft models according to the results of nude mice in vivo image detection, H&E pathological examination, and immunohistochemical detection of p16/Ki-67 protein expression. Collectively, all the results, particularly studies in vivo, demonstrated that VO(hntdtsc)(NPIP) hold a potential to be the lead compound and further to be an anticervical cancer drug.

Ginaton improves neurological function in ischemic stroke rats via inducing autophagy and maintaining mitochondrial homeostasis.

PURPOSE: The present study was carried out to confirm the protective effect of extract of Ginkgo biloba (Ginaton) against ischemic neuronal damage post-treatment at 24 h after reperfusion in rats with middle cerebral artery occlusion (MCAO) and further reveal its possible mechanisms. METHODS: Adult male Sprague-Dawley rats were modeled by MCAO for 2 h. The rats were divided into three groups: sham, model, and Ginaton (50 mg/kg). All animals received treatment once a day for 14 days from 24 h after reperfusion. Modified neurological severity score test was performed in 1, 7 and 14 days after MCAO, and beam walking test was performed only 14 days after MCAO. Hematoxylin-eosin straining was implemented to measure infarct volume and immunohistochemical analysis was performed to calculate the number of neurons in ischemic cortex penumbra. Western blot was used to evaluate the expression of autophagy (Beclin1, LC3, AMPK, mTOR, ULK), mitochondrial dynamic protein (Parkin, DRP1, OPA1) and apoptosis (Bcl-2, Bax). RESULTS: Post-treatment with Ginaton for 14 days decreased neurological deficit score, promoted the recovery of motor function, and noticeably reduced infarct size. Besides, Ginaton also alleviated the loss of NeuN-positive cells in ischemic cortex penumbra. In ischemic cortex, Ginaton increased the expression of Beclin1 and LC3-Ⅱ, elevated the AMPK, mTOR and ULK1, and induced autophagy. Moreover, Ginaton treatment upregulated Parkin, DRP1, and OPA1, and elevated the ratio of Bcl-2/Bax in 14 days after MCAO reperfusion injury. CONCLUSION: Ginaton exhibited obvious neuroprotective effects in MCAO rats with initial administered 24 h after MCAO. The mechanism of Ginaton included induction of autophagy via activation of the AMPK pathway, maintenance of mitochondrial homeostasis and inhibition of apoptosis.