Cycloastragenol inhibits adipogenesis and fat accumulation in vitro and in vivo through activating Hedgehog signaling.

In this study, we investigated the effect of cycloastragenol (CAG), a triterpenoid isolated from Astragalus membranaceus roots, on regulating the adipogenesis and fat accumulation in vitro and in vivo. During the adipogenesis of 3T3-L1 cells, CAG inhibited lipid accumulation and the expression of key adipogenic factors, proliferator-activated receptor γ (PPARγ) and CCAAT enhancer binding protein α (C/EBPα) and increased the expression of Gli1, a key mediator in Hedgehog (Hh) signaling. In HFD-induced animal experiment, CAG significantly reduced body weight gain without affecting brown fat weight. In addition, CAG regulated the expression of PPARγ, C/EBPα, and Gli1 in visceral white adipose tissue (vWAT). We also confirmed the inhibitory effect of CAG on specifically targeting white adipose tissue (WAT) formation in stromal vascular fraction (SVF) cell differentiation. Taken together, these results suggest that CAG may be a potent phytochemical preventing adipogenesis and obesity via Hh signaling. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01403-0.

Curcumol metabolized by rat liver S9 fraction and orally administered in mouse suppressed the proliferation of colon cancer in vitro and in vivo.

Following 3R (reduction, refinement, and replacement) principles, we employed the rat liver S9 fraction to mimic liver metabolism of curcumol having high in vitro IC50 on cancer cells. In HCT116 and HT29 colon cancer cells, the metabolites of curcumol by S9 fraction exerted more enhanced activity in inducing cell cycle arrest and apoptosis via regulating the expression of cyclin D1, CDK1, p21, PARP and Bcl-2 than curcumol. In addition, oral administration of curcumol at 4 mg/kg BW significantly suppressed the development of colon tumor induced by azoxymethane/dextran sulfate sodium, and induced cell cycle arrest and apoptosis in tumor tissues. In mass analysis, curcumenol and curzerene were identified as the metabolites of curcumol by S9 fraction metabolism. Taken together, curcumol metabolites showed the enhanced suppressive effect on colon cancer, suggesting that S9 fraction can be considered as simple, fast, and bio-mimicking platform for the screening of chemical libraries on different chronic diseases.

A 2-decade bibliometric analysis of epigenetics of cardiovascular disease: from past to present.

BACKGROUND: Cardiovascular disease (CVD) remains a major health killer worldwide, and the role of epigenetic regulation in CVD has been widely studied in recent decades. Herein, we perform a bibliometric study to decipher how research topics in this field have evolved during the past 2 decades. RESULTS: Publications on epigenetics in CVD produced during the period 2000-2022 were retrieved from the Web of Science Core Collection (WoSCC). We utilized Bibliometrix to build a science map of the publications and applied VOSviewer and CiteSpace to assess co-authorship, co-citation, co-occurrence, and bibliographic coupling. In total, 27,762 publications were included for bibliometric analysis. The yearly amount of publications experienced exponential growth. The top 3 most influential countries were China, the United States, and Germany, while the most cited institutions were Nanjing Medical University, Harbin Medical University, and Shanghai Jiao Tong University. Four major research trends were identified: (a) epigenetic mechanisms of CVD; (b) epigenetics-based therapies for CVD; (c) epigenetic profiles of specific CVDs; and (d) epigenetic biomarkers for CVD diagnosis/prediction. The latest and most important research topics, including "nlrp3 inflammasome", "myocardial injury", and "reperfusion injury", were determined by detecting citation bursts of co-occurring keywords. The most cited reference was a review of the current knowledge about how miRNAs recognize target genes and modulate their expression and function. CONCLUSIONS: The number and impact of global publications on epigenetics in CVD have expanded rapidly over time. Our findings may provide insights into the epigenetic basis of CVD pathogenesis, diagnosis, and treatment.

Correction to: Capsicum annuum L. cv. DANGJO ameliorated hyperglycemia in type 2 diabetes animal model induced by high-fat diet and streptozotocin.

[This corrects the article DOI: 10.1007/s10068-022-01068-1.].

Correction to: 1,3,5,8­Tetrahydroxyxanthone suppressed adipogenesis via activating Hedgehog signaling in 3T3­L1 adipocytes.

[This corrects the article DOI: 10.1007/s10068-022-01130-y.].

Synergistic Effects of the Ni3B Cocatalyst and N Vacancy on g-C3N4 for Effectively Enhanced Photocatalytic N2 Fixation.

The photocatalytic fixation of N2 is a promising technology for sustainable production of ammonia, while the unsatisfactory efficiency resulting from the low electron-transfer rate, narrow light absorption range, and limited active sites of the photocatalyst seriously hinder its application. Herein, we designed a noble metal-free Schottky junction photocatalyst constructed by g-C3N4 nanosheets with N vacancies (VN-CN) and metallic Ni3B nanoparticles (Ni3B/VN-CN) for N2 reduction to ammonia. The ammonia yield rate over the optimized Ni3B/VN-CN is 7.68 mM g-1 h-1, which is 6.7 times higher than that of pristine CN (1.15 mM g-1 h-1). The superior photocatalytic N2 fixation performance of Ni3B/VN-CN can be attributed not only to the formation of Schottky junctions between Ni3B and VN-CN, which facilitates the migration and separation of photogenerated electrons, but also to the incorporation of VN into g-C3N4, which enhances visible light absorption and improves electrical conductivity. More importantly, Ni3B nanoparticles can act as the cocatalyst, which provide more active sites for the adsorption and activation of N2, thereby improving the N2 reduction activity. This work provides an effective strategy of designing noble metal-free-based cocatalyst photocatalyst for sustainable and economic N2 fixation.

Relationship Between Prognostic Nutritional Index and New-Onset Atrial Fibrillation in Patients with Acute ST-Elevation Myocardial Infarction Following Percutaneous Coronary Intervention.

Multiple reports relate new-onset atrial fibrillation (NOAF) to poor clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) who received percutaneous coronary intervention (PCI). The prognostic nutritional index (PNI) is a reliable indicator of immunonutritional-inflammatory status, and it is linked to clinical outcomes in cardiovascular disease patients. This research aims to explore the relationship between NOAF and PNI.Overall, 600 STEMI patients treated with PCI were recruited for this retrospective analysis. The patients were categorized into the NOAF group or sinus rhythm (SR) group. Logistic regression and receiver operating characteristic (ROC) curve analyses were conducted to assess PNI estimation. Lastly, the Kaplan-Meier curve was used to compare all-cause mortality between both groups.The combined NOAF incidence in PCI-treated STEMI patients was 7.7%. PNI was independently correlated with NOAF using multivariate regression analyses (odds ratio [OR], 0.824; 95% confidence interval [CI], 0.750-0.906; P < 0.001). In ROC curve analyses, the best PNI threshold value for predicting NOAF was 40.1, with sensitivity, and specificity of 76.09% and 71.30%, respectively area under the curve, 0.787; 95% CI, 0.752-0.819; P < 0.001). After a median of 41-month follow-up, the Kaplan-Meier curve revealed that the NOAF patients displayed an elevated all-cause death incidence compared with SR patients, with a log-rank of P = 0.005.This study demonstrated that PNI is an independent predictor of NOAF in STEMI patients during hospitalization after PCI, which is strongly correlated with a poor outcome upon discharge.

Trends in worldwide research on cardiac fibrosis over the period 1989-2022: a bibliometric study.

Background: Cardiac fibrosis is a hallmark of various end-stage cardiovascular diseases (CVDs) and a potent contributor to adverse cardiovascular events. During the past decades, extensive publications on this topic have emerged worldwide, while a bibliometric analysis of the current status and research trends is still lacking. Methods: We retrieved relevant 13,446 articles on cardiac fibrosis published between 1989 and 2022 from the Web of Science Core Collection (WoSCC). Bibliometrix was used for science mapping of the literature, while VOSviewer and CiteSpace were applied to visualize co-authorship, co-citation, co-occurrence, and bibliographic coupling networks. Results: We identified four major research trends: (1) pathophysiological mechanisms; (2) treatment strategies; (3) cardiac fibrosis and related CVDs; (4) early diagnostic methods. The most recent and important research themes such as left ventricular dysfunction, transgenic mice, and matrix metalloproteinase were generated by burst analysis of keywords. The reference with the most citations was a contemporary review summarizing the role of cardiac fibroblasts and fibrogenic molecules in promoting fibrogenesis following myocardial injury. The top 3 most influential countries were the United States, China, and Germany, while the most cited institution was Shanghai Jiao Tong University, followed by Nanjing Medical University and Capital Medical University. Conclusions: The number and impact of global publications on cardiac fibrosis has expanded rapidly over the past 30 years. These results are in favor of paving the way for future research on the pathogenesis, diagnosis, and treatment of cardiac fibrosis.

Perilla oil and α-linolenic acid ameliorated thrombosis in rats induced by collagen and epinephrine.

Perilla frutescens is an annual herbaceous plant widely cultivated for oil production in China, Japan, and Korea. In this study, we investigated the effect of perilla oil (PO) on thrombosis induced by collagen and epinephrine (CE) in rats. The oral administration of PO significantly increased prothrombin time (PT) and activated partial thromboplastin time (aPTT) in the blood plasma and inhibited the expression of cells adhesion markers (CAMs) such as intercellular CAM-1 (ICAM-1), vascular CAM (VCAM-1), E-selectin and P-selectin in the aorta tissue. Furthermore, pulmonary occlusion induced by CE in rats was suppressed by PO. α-Linolenic acid (ALA) was quantified at 60.14 ± 2.50 g/100 g of PO, and its oral administration at the same concentration with that in PO exerted the similar effect on PT, aPTT, ICAM-1, VCAM-1, E-selectin and P-selectin in CE-induced thrombosis rats. Taken together, PO and ALA significantly ameliorated thrombosis by regulating CAMs.

Bismuth nanoparticles and oxygen vacancies synergistically modified HNb3O8 nanosheets for enhanced photocatalytic N2 reduction towards NH3.

Due to the high stability of the N2 molecule and the low charge separation efficiency, the photocatalytic reduction of N2 to high-value chemicals (NH3) under mild conditions remains a great challenge. Herein, a composite photocatalyst (Bi/HNb3O8-Vo nanosheets) with Bi nanoparticles modified the HNb3O8-Vo nanosheets are designed for the conversion of N2 into NH3. In this design, the introduction of oxygen vacancies on the catalyst surface facilitates the formation of defective energy levels within the band gap of HNb3O8-Vo NS, which promotes the absorption of visible light, and enhances the charge carrier transport and separation. Bi nanoparticles co-catalyst not only facilitates the separation and migration of photogenerated charges, but also acts as reaction sites to adsorb and activate N2 molecule. Consequently, the optimized 5 % Bi/HNb3O8-Vo photocatalysts show a NH3 yield of 372.7 µmol/L g-1h-1 under full spectral irradiation without sacrificial agent, which is much higher than that of HNb3O8 NS (92.2 µmol/L g-1h-1). This work provides a new way for the design of efficient N2 reduction photocatalysts through the synergistic effect of surface vacancies and metal co-catalysts.

Hyperammonemia in a pregnant woman with citrullinemia type I: a case report and literature review.

BACKGROUND: Citrullinemia type I (CTLN1) is a rare urea cycle disorder (UCD) with few adult cases described so far. Diagnosis of late-onset CTLN1 is difficult, and delayed treatment may increase the risk of severe hyperammonemia. Pregnancy is an important risk factor for women with CTLN1. However, the clinical manifestations of CTLN1 in a pregnant woman may be mistaken for pregnancy side effects and ultimately delay a timely diagnosis. CASE PRESENTATION: A 34-year-old woman developed vomiting and disturbance of consciousness after 12 weeks of gestation. A blood test showed hyperammonemia (454 µg/dL) with normal liver function tests. She fell into a deep coma, and her serum ammonia level increased to 800 µg/dL. Continuous renal replacement therapy (CRRT) was administered as a diagnostic treatment for UCD and serum ammonia. This patient's case was complicated by co-infection; her dependents decided to withdraw life support and the patient died. She was diagnosed with CTLN1 by analyses of plasma amino acids, urinary orotic acid, and second-generation gene sequencing. DISCUSSION AND CONCLUSION: When a patient displays symptoms of emesis and disturbance of consciousness in early pregnancy, blood ammonia should be monitored, and UCD should be considered, particularly for patients with hyperammonemia in the absence of severe liver function abnormalities.

Ni3B as p-Block Element-Modulated Cocatalyst for Efficient Photocatalytic CO2 Reduction.

Due to the multiple electron and proton transfer processes involved, the photogenerated charges are easily recombined during the photocatalytic reduction of CO2, making the generation of the eight-electron product CH4 kinetically more difficult. Herein, Ni3B nanoparticles modulated by p-block element were combined with TiO2 nanosheets to construct a novel Schottky junction photocatalyst (Ni3B/TiO2) for the selective photocatalytic conversion of CO2 to CH4. The formed Ni3B/TiO2 photocatalyst with Schottky junction ensures a transfer pathway of photogenerated electrons from TiO2 to Ni3B, which facilitates the accumulation of electrons on the surface of Ni3B and subsequently improves the activity of photocatalytic CO2 reduction to CH4. The optimized Ni3B/TiO2 Schottky junction shows an improved CH4 yield of 30.03 µmol g-1 h-1, which was much higher than those of TiO2 (1.62 µmol g-1 h-1), NiO/TiO2 (2.44 µmol g-1 h-1), and Ni/TiO2 (4.3 µmol g-1 h-1). This work demonstrated that the introduction of p-block elements can alleviate the scaling relationship effect of pure metal cocatalysts to a certain extent, and the modified Ni3B can be used as a promising new cocatalyst to effectively improve the selective photocatalytic of CO2 to CH4.

1,3,5,8-Tetrahydroxyxanthone suppressed adipogenesis via activating Hedgehog signaling in 3T3-L1 adipocytes.

In this study, we investigated the effect of 1,3,5,8-tetrahydroxyxanthone (THX) on the adipogenesis of 3T3-L1 adipocytes. THX, a xanthone isolated from Gentianella acuta, inhibited lipid accumulation in 3T3-L1 adipocytes and reduced the protein levels of the key adipogenic transcriptional factors, peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein α (C/EBPα), in a dose-dependent manner. In addition, THX enhanced the transcriptional activity of Gli1 known as the key indicator of Hedgehog (Hh) signaling activity and increased the expression of Gli1 and its upstream regulator Smo. The Smo activator SAG exerted the similar effect with THX on regulating Gli1, Smo, PPARγ and C/EBPα expression, which led to the suppression of fat formation in 3T3-L1 adipocytes. Furthermore, we found that the inhibitory effect of THX on adipogenesis was derived from regulation of the early stage of adipogenesis. These results suggest that THX suppresses the differentiation of adipocyte through Hh signaling and may be considered as a potent agent for the prevention of obesity.

IL-6 inhibitors effectively reverse post-infarction cardiac injury and ischemic myocardial remodeling via the TGF-ß1/Smad3 signaling pathway.

Approximately one in four myocardial infarctions occur in older patients. The majority of therapeutic advances are either not appropriate or not tested in elderly patients. The main reasons for deviating from the guidelines are justified concerns regarding the effectiveness of the recommended forms of therapy, fear of adverse drug reactions and ethical concerns. Targeting interleukin 6 (IL-6) for ventricular remodeling after cardiovascular damage is a feasible alternative to standard polypharmaceutics, but the underlying molecular mechanisms are not well understood. Continuous activation of the IL-6-associated cytokine receptor gp130 leads to cardiomyopathic hypertrophy. TGFß1 is involved in forming fibrosis in various organs, and its overexpression can cause myocardial hypertrophy and fibrosis. Il-6 has been hypothesized to be indirectly involved in cardiac remodeling via the TGFß1/Smad signaling transduction pathway. In the present study, a rat model of acute myocardial ischemia, IL-6 and IL-6 receptor blockers were injected directly into the necrotic myocardium. Changes in cardiac function, myocardial infarction area, myocardial collagen, necrotic myocardial fibrosis and levels of TGFß1, IL-6 and MMP2/9 were quantified in myocardial tissue fibrosis by ELISA. The present study demonstrated that IL-6 stimulated myocardial fibrosis through the TGFß1-Smad-MM2/9 signaling transduction pathway. Overall, this provided a solid foundation for understanding the relationship between IL-6 and ventricular remodeling.

Capsicum annuum L. cv. DANGJO ameliorated hyperglycemia in type 2 diabetes animal model induced by high-fat diet and streptozotocin.

In this study, it was evaluated the effect of freeze-dried powder of Capsicum annuum L. cv. DANGJO (DJ) on ameliorating hyperglycemia in type 2 diabetes rat model induced by high-fat diet (HFD) and streptozotocin (STZ). Oral administration of DJ significantly reduced non-fasting blood glucose (NFBG) and insulin levels, as well as glycated hemoglobin (HbA1c) level, a representative marker for diabetes, in HFD/STZ treated rats whereas the administration of green hot pepper (GHP) and green sweet pepper (GSP) did not show the significant effect. Quercitrin was quantified (40.97 mg/100 g of DJ) by HPLC, and administration of the same amount of quercitrin with DJ exerted the significant reduction of blood glucose level, strongly supporting that quercitrin is the key component in ameliorating the hyperglycemia of DJ in HFD/STZ treated rats. These results suggest that DJ can be considered as a potent functional food in preventing hyperglycemia in type 2 diabetes mellitus.

Garcinone C Suppresses Tumorsphere Formation and Invasiveness by Hedgehog/Gli1 Signaling in Colorectal Cancer Stem-like Cells.

Hyperactivation of hedgehog signaling occurs in colorectal cancer stem-like cells (CSCs), a rare subpopulation, potentially involved in metastasis, chemotherapy resistance, and cancer relapse. Garcinone C, a xanthone isolated from mangosteen (Garcinia mangostana), suppresses colorectal cancer in vivo and in vitro by inhibiting Gli1-dependent noncanonical hedgehog signaling. Herein, we investigated the effect of garcinone C on cancer stemness and invasiveness in colorectal cancer; Gli1 was noted as pivotal in maintaining stemness and invasiveness in HCT116 and HT29 CSCs. Garcinone C inhibited the proliferation and self-renewal of HCT116 and HT29 CSCs. Colon cancer stemness markers such as CD44, CD133, ALDH1, and Nanog were significantly decreased by garcinone C. Computational studies showed that garcinone C showed a high affinity with the Gli1 protein ZF domain by forming hydrogen bonds with amino acid residues of ASP244, ARG223, and ASP216. Besides, MG132 blocked the effects of garcinone C on Gli1. Thus, garcinone C suppressed colorectal CSCs by binding to Gli1 and enhancing its degradation. MMP2 and MMP9 levels, invasive-related markers, were increased in HCT116 CSCs but decreased by garcinone C. E-cadherin level was reduced in HCT116 CSCs, while the presence of garcinone C was restored. Garcinone C inhibited the proliferation and invasiveness of colorectal CSCs by targeting Gli1-dependent Hh signaling. Garcinone C may be a potent natural agent against colorectal cancer relapse.

Carbon vacancy-mediated exciton dissociation in Ti3C2Tx/g-C3N4 Schottky junctions for efficient photoreduction of CO2.

Earth-abundant g-C3N4 is a promising photocatalyst for CO2 reduction, but its practical application is severely limited by the excitonic effect of g-C3N4 derived from strong binding energy and lack of electron-enriched active sites. Herein, we design a novel 2D/2D Schottky junction photocatalysts comprising of Ti3C2Tx-modified defective g-C3N4 nanosheets with carbon vacancy (denoted as Ti3C2Tx/Vc-CN) by a self-assembly method. The carbon vacancies in g-C3N4 promote exciton dissociation into free charge, while the formed Schottky junctions between Ti3C2Tx and Vc-CN further enables a directional charge transfer, thus providing an electron-rich catalytic surface for the CO2 reduction. Thanks to the synergy of promoted exciton dissociation and directional electron transfer, the optimal 20% Ti3C2Tx/Vc-CN display a high CO evolution rate of 20.54 µmol·g-1·h-1 under visible light irradiation, which is 7.4 times higher than that of bare CN. This work highlights the synergy of the promoted exciton dissociation and directional electron transfer in the activity enhancement of photocatalytic CO2 reduction.

GATA2/FGF21 Axis Regulates the Effects of High Glucose on the Apoptosis, Autophagy and Oxidative Stress of Human Umbilical Vein Endothelial Cell via PI3K/AKT/mTOR Pathway.

OBJECTIVE: We investigated the role and mechanism of GATA-binding factor 2/Fibroblast growth factor 21 (GATA2/FGF21) axis in high glucose (HG)-induced injury in human umbilical vein endothelial cells (HUVEC). METHODS: After HG treatment and transfection, the viability and apoptosis of HUVECs were determined via Cell Counting Kit-8 and Hoechst 33258 staining methods, and the content of lactate dehydrogenase (LDH) and reactive oxygen species (ROS) was measured via colorimetric assay and DCFH-DA staining. The potential transcription factor of FGF21 was predicted with bioinformatic analysis and confirmed via dual-luciferase reporter assay and chromatin immunoprecipitation. The expressions of GATA2/FGF21, apoptosis-, autophagy- and phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway-related factors were quantified with quantitative real-time polymerase chain reaction or Western blot. RESULTS: Overexpressed FGF21 abolished the effects of HG on repressing the expressions of FGF21 and cell viability, and promoting apoptosis, the levels of LDH and ROS and autophagy in HUVECs, with increased Bcl-2 and p62 expression yet decreased Bax, Cleaved PARP, Cleaved caspase-3, LC3 II/LC3 I ratio and Beclin 1. GATA2 was the transcription factor of FGF21 and was downregulated after HG treatment, and the effects of overexpressed FGF21 in HG-treated HUVECs were all reversed after the silence of GATA2. Besides, overexpressed FGF21 promoted the activation of PI3K/AKT/mTOR pathway, with increased phosphorylation levels of PI3K, AKT and mTOR, whereas silencing GATA2 abolished the trend. CONCLUSION: GATA2/FGF21 axis has a protective function against HG in HUVEC via regulating PI3K/AKT/mTOR pathway.

Suppression of Adipogenesis and Fat Accumulation by Vitexin Through Activation of Hedgehog Signaling in 3T3-L1 Adipocytes.

Many studies have demonstrated that adipogenesis is associated with obesity, and the Hedgehog (Hh) signaling pathway regulates adipogenesis and obesity. Following the screening study of the chemical library evaluating the effect of vitexin on Gli1 transcriptional activity, vitexin was chosen as a candidate for antiadipogenic efficacy. Vitexin significantly reduced lipid accumulation and suppressed C/EBPα (CCAAT/enhancer-binding protein α) and PPARγ (peroxisome proliferator-activated receptor γ) expression, which are known as key adipogenic factors in the early stages of adipogenesis by activating Hh signaling. Furthermore, Hh inhibitor GANT61 reversed the effect of AMP-activated protein kinase (AMPK) activator AICAR (5-aminoimidazole-4-carboxamide ribonucleotide), indicating that Hh signaling is an upstream regulator of AMPK in 3T3-L1 cells. Vitexin suppressed adipogenesis by regulating Hh signaling and phosphorylation of AMPK, leading to the inhibition of fat formation. These results suggest that vitexin can be considered a potent dietary agent in alleviating lipid accumulation and obesity.

Photocatalytic reduction of CO2 into CH4 over Ru-doped TiO2: Synergy of Ru and oxygen vacancies.

Photocatalytic conversion of CO2 and H2O into CH4 is an intriguing approach to achieve solar energy utilization and CO2 conversion, yet remains challenging in conversion efficiency. In this study, we present a synthesis of defected TiO2 nanocrystal with oxygen vacancies (Vo) by a facile Ru doping-induced strategy under hydrothermal condition. The synergistic effect of Ru and oxygen vacancies contributed to the enhanced photocatalytic reduction of CO2 toward CH4. Oxygen vacancies and doped Ru not only can synergistically promote the separation of photogenerated carriers, but also promote the CO2 adsorption, thus enhancing the photocatalytic activities. The optimal Ru-doped TiO2 (denoted as 1% Ru-TiO2-x) exhibited a remarkable enhanced photocatalytic performance with a CH4 yield of 31.63 µmol·g-1·h-1, which is significantly higher than Ru-TiO2 and TiO2-x counterparts. This study systematically investigates the multiple roles of Ru in CO2 reduction and provides new insights for the construction of metal oxide photocatalysts with oxygen vacancies by simple doping of metal ions.