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Myocardial remodeling (MR) following myocardial infarction (MI) contributes to heart failure. Inflammation is a key determinant in cardiac remodeling, with potential prognostic improvements by inhibiting inflammatory factors. Pattern recognition receptors, including interferon gamma-inducible protein-16 (IFI-16), play significant roles in this process, yet its specific involvement remains underexplored. This study investigates IFI-16's role in initiating inflammation via the inflammasome and its direct interaction with galectin-3 protein post-MI. Elevated IFI-16 levels were observed in human and rat myocytes and a mouse MI model under hypoxic, nutrient-deprived conditions, correlating with increased inflammation-associated proteins. Suppression of IFI-16/IFI-204 using short hairpin RNA (shRNA) lentivirus or adeno-associated virus decreased inflammatory factor activation, thereby mitigating remodeling and enhancing cardiac function post-MI. Co-immunoprecipitation (coIP) and double-fluorescence staining confirmed IFI-16's ability to interact directly with galectin-3. These findings underscore IFI-16's critical role as a pro-inflammatory factor in post-MI MR, suggesting its inhibition as a potential therapeutic strategy.
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Resistance to chemotherapy leads to poor prognosis for osteosarcoma (OS) patients. However, due to the high metastasis of tumor and the decrease in sensitivity of tumor cells to cisplatin (DDP), the 5-year survival rate of OS patients is still unsatisfactory. This study explored a mechanism for improving the sensitivity of OS cells to DDP. A DDP-resistant OS cell model was established, and we have found that circORC2 and TRIM2 were upregulated in DDP-resistant OS cells, but miR-485-3p was downregulated. The cell viability and proliferation of the OS cells decreased gradually with the increase of DDP dose, but a gradual increase in apoptosis was noted. CircORC2 promoted OS cell proliferation and DDP resistance and upregulated TRIM2 expression by targeting miR-485-3p. Functionally, circORC2 downregulated miR-485-3p to promote OS cell proliferation and inhibit DDP sensitivity. Additionally, it promoted cell proliferation and inhibited the sensitivity of DDP by regulating the miR-485-3p/TRIM2 axis. In conclusion, circORC2 promoted cell proliferation and inhibited the DDP sensitivity in OS cells via the miR-485-3p/TRIM2 axis. These findings indicated the role of circORC2 in regulating the sensitivity of OS cells to DDP.
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Aims: To systematically evaluate the comprehensive effect of combining Naoxintong capsule (NXT) with Western medicine (WM) on coronary heart disease post-percutaneous coronary intervention (PCI). Methods: Randomized controlled trials (RCTs) of NXT for patients with CHD after PCI were systematically searched across multiple databases, including the Cochrane Library, PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI), Chinese Science and Technology Journal Database (VIP), and Wan Fang, from inception until 31 January 2023. Study selection, data extraction, and quality assessment were performed by two independent reviewers. The quality of the included studies was evaluated using version 2 of the Cochrane risk-of-bias tool (RoB 2), and data analysis was performed using R4.2.2. Results: Fifteen RCTs conducted between 2011 and 2022 and involving 1,551 patients were identified, with 774 and 777 patients in the experimental and control groups respectively. It was found that the NXT and WM combination was superior to the WM therapy alone in terms of the effective clinical rate (odds ratio [OR] = 4.69, 95% confidence interval [CI] = 2.13-10.30), effective rate in electrocardiogram (OR = 6.92, 95% CI = 3.44-13.92), effective rate in angina (OR = 5.90, 95% CI = 3.04-11.46), left ventricular ejection fraction (mean difference [MD] = 4.94, 95% CI = 2.89-6.99), brain natriuretic peptide (MD = -294.00, 95% CI = -584.60 to -3.39), creatine kinase-MB (MD = -7.82, 95% CI = -13.26 to -2.37), major adverse cardiovascular events (OR = 0.24, 95% CI = 0.14-0.43), maximum platelet aggregation rate (MD = -8.33, 95% CI = -11.64 to -5.01), and Chinese medicine evidence score (OR = 9.79, 95% CI = 3.57-26.85). However, there was no significant difference in cardiac troponin I level reduction (MD = -0.13, 95% CI = 0.35-0.09) or the occurrence of adverse medicine events (OR = 0.92, 95% CI = 0.41-2.05). Meta-regression and subgroup analyses indicated that NXT capsule dosage, treatment duration, and patient baseline characteristics contributed to the heterogeneity. Conclusion: A combination of NXT and WM can improve clinical outcomes in patients undergoing PCI. However, further studies are needed to confirm the reliability and safety of this combined treatment approach. Systematic Review Registration: PROSPERO, https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=369174, Identifier CRD42022369174.
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Pyroptosis is an innate immune response triggered by the activation of inflammasomes by various influencing factors, characterized by cell destruction. It impacts the immune system and cancer immunotherapy. In recent years, the roles of pyroptosis and inflammasomes in intestinal inflammation and cancer have been continuously confirmed. This article reviews the latest progress in pyroptosis mechanisms, new discoveries of inflammasomes, mutual regulation between inflammasomes, and their applications in intestinal diseases. Additionally, potential synergistic treatment mechanisms of intestinal diseases with pyroptosis are summarized, and challenges and future directions are discussed, providing new ideas for pyroptosis therapy.
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Enfermedades Intestinales , Neoplasias , Humanos , Piroptosis , Inflamasomas , Neoplasias/terapia , Inflamación , Enfermedades Intestinales/terapiaRESUMEN
Per- and polyfluoroalkyl substances (PFAS) can disrupt liver homeostasis. Studies have shown that a single exposure to PFAS may provoke abnormal liver function; however, few studies have investigated the overall effect of PFAS mixtures. We aimed to investigate associations between exposure to PFAS mixtures and liver function indices and explore the relevant mechanisms. This study included 278 adult males from Guangzhou, China. Serum metabolite profiles were analyzed using untargeted metabolomics. We applied weighted quantile sum (WQS) regression as well as Bayesian kernel machine regression (BKMR) to analyze the association of nine PFAS mixtures with 14 liver function indices. PFAS mixtures were positively associated with apolipoprotein B (APOB) and gamma-glutamyltransferase (GGT) and negatively associated with direct bilirubin (DBIL) and total bilirubin (TBIL) in both the WQS and BKMR analyses. In addition, Spearman's correlation test showed individual PFAS correlated with APOB, GGT, TBIL, and DBIL, while there's little correlation between individual PFAS and other liver function indices. In linear regression analysis, PFHxS, PFOS, PFHpS, PFNA, PFDA, and PFUdA were associated with APOB; PFOA, PFDA, PFOS, PFNA, and PFUdA were associated with GGT. Subsequently, a metabolome-wide association study and mediation analysis were combined to explore metabolites that mediate these associations. The mechanisms linking PFAS to APOB and GGT are mainly related with amino acid and glycerophospholipid metabolism. High-dimensional mediation analysis showed that glycerophospholipids are the main markers of the association between PFAS and APOB, and that (R)-dihydromaleimide, Ile Leu, (R)-(+)-2-pyrrolidone-5-carboxylic acid, and L-glutamate are the main markers of the association between PFAS and GGT. In summary, overall associations between PFAS and specific indices of liver function were found using two statistical methods; the metabolic pathways and markers identified here may serve to prompt more detailed study in animal-based systems, as well as a similar detailed analysis in other populations.
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Ácidos Alcanesulfónicos , Contaminantes Ambientales , Fluorocarburos , Animales , Masculino , Teorema de Bayes , Apolipoproteínas B , Bilirrubina , HígadoRESUMEN
Dipeptidyl peptidase IV (DPP-IV) inhibitory peptides can regulate type 2 diabetes by inhibiting the cleavage of glucagon-like peptide-1 and prolonging its half-life. The development of DPP-IV inhibitory peptides is still a hot topic. The primary structure of coix seed prolamins contains peptide sequence fragments that potentially inhibit DPP-IV; however, limited information is available regarding the extraction of peptides from coix seeds and the analysis of their conformational relationships. In this study, novel coix seed prolamin-derived peptides were obtained through single hydrolysis and double-enzyme stepwise hydrolysis. The inhibitory activity of these peptides against DPP-IV was evaluated to explore new functional properties of coix seeds. The results evidenced that the step-by-step enzymolysis (papain and alcalase) compared to single enzymolysis promoted the secondary structure disruption of the hydrolysates, enhanced the ß-turn structure, significantly increased the content of peptides below 1 kDa, and exhibited a substantial increase in DPP-IV inhibitory activity (97% inhibition). Three nontoxic DPP-IV inhibitory peptides, namely, LPFYPN, TFFPQ, and ATFFPQ (IC50 = 70.24, 176.87, 268.31 µM), were isolated and identified. All three peptides exhibited strong interactions with DPP-IV (all KA values >103). LPFYPN exhibited competitive inhibition, while TFFPQ and ATFFPQ demonstrated mixed competitive-noncompetitive inhibition. Hydrogen bonding and hydrophobic interactions were the main contributors to the coix seed prolamin peptides binding to DPP-IV. The central residue was a key amino acid in the parent peptide sequence, forming a more stable π-π stacking with residues in the active pocket, which may facilitate peptide activity. This study provides theoretical support for the development of coix seed-derived hypoglycemic peptides.
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Dipeptidyl peptidase-IV (DPP-IV) is a key target for the treatment of type 2 diabetes mellitus. It is possible that peptides that precisely regulate DPP-IV could be released from coix seed prolamins (CSP), but whether this happens has not yet been investigated. We performed the in silico digestion of CSP and predicted the bioactivity, absorption, transport, toxicity, and allergenicity of the resulting peptides. The simulation predicted that 47 non-toxic bioactive peptides would be released. After screening these, we found that 64.58% of them could possess DPP-IV inhibitory activity. The effect of thermal processing on the amino acid composition and structural properties of CSP was determined, and the DPP-IV inhibitory activity of its digestion-derived peptides was also assessed. The results showed that processing could change the flavour of coix seed and the supply of amino acids. After processing, the spatial conformation of CSP changed from ordered to disordered, and the peptide content and the DPP-IV inhibitory activity of its digestion products significantly increased by 19.89-30.91% and 36.84-42.02%, respectively. These results support the hypothesis that processing can change the protein structure and increase the probability that bioactive peptides will be released. They also have important implications for the development of bioactive peptides and the intensive processing of coix seeds.
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During the storage and processing of mung beans, proteins and polyphenols are highly susceptible to interactions with each other. Using globulin extracted from mung beans as the raw material, the study combined it with ferulic acid (FA; phenolic acid) and vitexin (flavonoid). Physical and chemical indicators were combined with spectroscopy and kinetic methods, relying on SPSS and peak fit data to statistically analyze the conformational and antioxidant activity changes of mung bean globulin and two polyphenol complexes before and after heat treatment and clarify the differences and the interaction mechanism between globulin and the two polyphenols. The results showed that, with the increase in polyphenol concentration, the antioxidant activity of the two compounds increased significantly. In addition, the antioxidant activity of the mung bean globulin-FA complex was stronger. However, after heat treatment, the antioxidant activity of the two compounds decreased significantly. The interaction mechanism of the mung bean globulin-FA/vitexin complex was static quenching, and heat treatment accelerated the occurrence of the quenching phenomenon. Mung bean globulin and two polyphenols were combined through a hydrophobic interaction. However, after heat treatment, the binding mode with vitexin changed to an electrostatic interaction. The infrared characteristic absorption peaks of the two compounds shifted to different degrees, and new peaks appeared in the areas of 827 cm-1, 1332 cm-1, and 812 cm-1. Following the interaction between mung bean globulin and FA/vitexin, the particle size decreased, the absolute value of zeta potential increased, and the surface hydrophobicity decreased. After heat treatment, the particle size and zeta potential of the two composites decreased significantly, and the surface hydrophobicity and stability increased significantly. The antioxidation and thermal stability of the mung bean globulin-FA were better than those of the mung bean globulin-vitexin complex. This study aimed to provide a theoretical reference for the protein-polyphenol interaction mechanism and a theoretical basis for the research and development of mung bean functional foods.
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BACKGROUND: Atherosclerosis and depression contribute to each other; however, mechanisms linking them at the genetic level remain unexplored. This study aimed to identify shared gene signatures and related pathways between these comorbidities. METHODS: Atherosclerosis-related datasets were downloaded from the Gene Expression Omnibus database. Differential and weighted gene co-expression network analyses were employed to identify atherosclerosis-related genes. Depression-related genes were downloaded from the DisGeNET database, and the overlaps between atherosclerosis-related genes and depression-related genes were characterized as crosstalk genes. The functional enrichment analysis and protein-protein interaction network were performed in these gene sets. Subsequently, the Boruta algorithm and Recursive Feature Elimination algorithm were performed to identify feature-selection genes. A support vector machine was constructed to measure the accuracy of calculations, and two external validation sets were included to verify the results. RESULTS: Based on two atherosclerosis-related datasets (GSE28829 and GSE43292), 165 genes were determined as atherosclerosis-related genes. Meanwhile, 1478 depression-related genes were obtained. After intersecting, 24 crosstalk genes were identified, and two pathways, "lipid and atherosclerosis" and "tryptophan metabolism," were revealed as mutual pathways according to the enrichment analysis results. Through the protein-protein interaction network, Molecular Complex Detection plugin, and cytoHubba plugin, PTPRC and MMP9 were identified as the hub gene. Moreover, SLC22A3, CASP1, AMPD3, and PIK3CG were recognized as feature-selection genes. Based on two external validation sets, CASP1 and MMP9 were finally determined as the critical crosstalk genes. CONCLUSIONS: "Lipid and atherosclerosis" and "tryptophan metabolism" were possibly the pathways of atherosclerosis secondary to depression and depression due to atherosclerosis, respectively. CASP1 and MMP9 were revealed as the most pivotal candidates linking atherosclerosis and depression by mediating these two pathways. Further experimentation is needed to confirm these conclusions.
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Aterosclerosis , Transcriptoma , Humanos , Transcriptoma/genética , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Redes Reguladoras de Genes/genética , Depresión/genética , Triptófano , Aterosclerosis/genética , Perfilación de la Expresión Génica/métodos , Lípidos , Biología Computacional/métodosRESUMEN
BACKGROUND: Automatic segmentation of medical images has progressed greatly owing to the development of convolutional neural networks (CNNs). However, there are two uncertainties with current approaches based on convolutional operations: (1) how to eliminate the general limitations that CNNs lack the ability of modeling long-range dependencies and global contextual interactions, and (2) how to efficiently discover and integrate global and local features that are implied in the image. Notably, these two problems are interconnected, yet previous approaches mainly focus on the first problem and ignore the importance of information integration. METHODS: In this paper, we propose a novel cross-attention and cross-scale fusion network (CASF-Net), which aims to explicitly tap the potential of dual-branch networks and fully integrate the coarse and fine-grained feature representations. Specifically, the well-designed dual-branch encoder hammers at modeling non-local dependencies and multi-scale contexts, significantly improving the quality of semantic segmentation. Moreover, the proposed cross-attention and cross-scale module efficiently perform multi-scale information fusion, being capable of further exploring the long-range contextual information. RESULTS: Extensive experiments conducted on three different types of medical image segmentation tasks demonstrate the state-of-the-art performance of our proposed method both visually and numerically. CONCLUSIONS: This paper assembles the feature representation capabilities of CNN and transformer and proposes cross-attention and cross-scale fusion algorithms. The promising results show new possibilities of using cross-fusion mechanisms in more downstream medical image tasks.
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Algoritmos , Suministros de Energía Eléctrica , Redes Neurales de la Computación , Semántica , Procesamiento de Imagen Asistido por ComputadorRESUMEN
BACKGROUND: Delayed wound healing, a common problem in patients with diabetes mellitus (DM), is associated with impaired keratinocyte autophagy. Epigallocatechin gallate (EGCG), a catechin, has been proven to promote diabetic wound healing. This study aims to explore the therapeutic mechanism of EGCG on diabetic wound healing. METHODS: High glucose (HG)-induced keratinocytes and streptozotocin (STZ)-induced DM rats were prepared and intervened with EGCG to examine its therapeutic effects in in vivo and in vitro settings. The AMPK inhibitor, Compound C, was utilized to determine whether EGCG exerted its therapeutic effects through the AMPK/ULK1 pathway. RESULTS: In vitro, EGCG improved HG-induced autophagy impairment in keratinocytes by increasing LC3II/LC3I, Becline1, and ATG5 levels and decreasing p62 level. Mechanically, EGCG activated the AMPK/ULK1 pathway, thereby promoting keratinocyte autophagy through the phosphorylation of AMPK and ULK1. Notably, EGCG promoted the proliferation, migration, synthesis and release of C-C motif chemokine ligand 2 (CCL2) in HG-treated keratinocytes. Furthermore, EGCG indirectly promoted the activation of fibroblasts, as evidenced by increased alpha-smooth muscle actin (α-SMA) and Collagen I levels. In vivo, EGCG promoted wound healing in DM rats, primarily by reducing inflammatory infiltration and increasing granulation tissue to promote wound epithelialization. Besides, EGCG promoted ATG5, KRT10, KRT14, TGF-ß1, Collagen I, and α-SMA expressions in the neonatal epithelial tissues of DM rats. However, the use of Compound C reversed the effects of EGCG. CONCLUSIONS: These findings indicated that EGCG restored keratinocyte autophagy to promote diabetic wound healing through the AMPK/ULK1 pathway.
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Autofagia , Catequina , Diabetes Mellitus Experimental , Queratinocitos , Cicatrización de Heridas , Animales , Ratas , Proteínas Quinasas Activadas por AMP/metabolismo , Homólogo de la Proteína 1 Relacionada con la Autofagia/metabolismo , Catequina/farmacología , Colágeno , Diabetes Mellitus Experimental/tratamiento farmacológico , Péptidos y Proteínas de Señalización Intracelular , Queratinocitos/metabolismoRESUMEN
The nutrition and functionality of Chenopodium quinoa Willd are closely related to its components; however, these properties vary widely in different varieties of C. quinoa Willd from different origins. Using ultrahigh-performance liquid chromatography coupled with high-field quadrupole-orbitrap high-resolution mass spectrometry (UHPLC-QE HF HRMS) for metabolomics analysis, we performed nontargeted metabolomics analysis of C. quinoa Willd of different color varieties and origins and evaluated the texture characteristics after cooking. Both the variety and origin significantly affected the metabolic characteristics of C. quinoa Willd. The differences in the composition and texture properties were closely related to the lipid, amino acid, and polyphenol contents. The contents of kaempferol, catechol, myricetin 7-(6'-galloside), tyrosine, prostaglandin I2, and glutathione in white, red, and black quinoa significantly differed, and the variety had a greater effect on the lipid content than on the polyphenol and amino acid contents. At the same processing level, the texture properties of white and red quinoa were better than those of black quinoa. Furthermore, the contents of differential polyphenols and amino acids in Gansu white quinoa were higher than those in quinoa from the other three producing areas. The contents of differential polyphenols and terpenoids in Inner Mongolia white quinoa were relatively low, whereas in Shanxi white quinoa, the contents of differential amino acids were relatively low and those of differential terpenoids were relatively high. The levels of quercetin and its derivatives, kaempferol and its derivatives, 9-HODE, azelaic acid, sebacic acid, elaidic acid, linoleic acid, prostaglandin H2, glutathione, 5-aminovaleric acid, and other compounds significantly differed in quinoa from different origins; thus, these compounds can be used as metabolic markers to identify the origin of quinoa. The texture properties of white quinoa from Qinghai and Inner Mongolia were better than those of white quinoa from Gansu and Shanxi. Although C. quinoa Willd can tolerate harsh environments, its grain quality varies widely. Cultivating C. quinoa Willd varieties according to local conditions is important for improving their yield and quality.
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Chenopodium quinoa , Quempferoles , Polifenoles , Cromatografía Liquida , Espectrometría de Masas , Semillas , Aminoácidos , Glutatión , LípidosRESUMEN
In this study, multiple-impurity adsorption purification (MIA) technologies and liquid chromatography−tandem mass spectrometry (LC-MS/MS) were used to establish a method for detecting 11 mycotoxins in maize. The conditions for mass spectrometry and MIA were optimized. Maize was extracted with 70% acetonitrile solution, enriched, and purified using MIA technologies, and then, analyzed via LC-MS/MS. The results showed that the linear correlation coefficients of the 11 mycotoxins were >0.99, the sample recoveries ranged from 77.5% to 98.4%, and the relative standard deviations were <15%. The validated method was applied to investigate actual samples, and the results showed that the main contaminating toxins in maize were aflatoxins (AFs), deoxynivalenol (DON), fumonisins (FBs), ochratoxin A (OTA), and zearalenone (ZEN). Additionally, simultaneous contamination by multiple toxins was common. The maximum detection values of the mycotoxins were 77.65, 1280.18, 200,212.41, 9.67, and 526.37 µg/kg for AFs, DON, FBs, OTA, and ZEN, respectively. The method is simple in pre-treatment, convenient in operation, and suitable for the simultaneous determination of 11 types of mycotoxins in maize.
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In this study, a method, based on an ultraperformance liquid chromatography coupled with high-field quadrupole orbitrap high-resolution mass spectrometry (UHPLC-QE-HF-HRMS) platform, was established for the trace determination of three major avenanthramides (AVNs). The MS conditions for determining the AVNs were optimized, and the cracking methods of avenanthramides were analyzed. The linear range of the results and the correlation coefficient were 1−2000 µg/L and >0.996, respectively. Further, the established method was employed for the determination of the AVN contents of oats at different germination times, and the results indicated that the AVN contents of Zaohua and Bayou oats increased 19.26 and 6.09 times, respectively, after germination. The total AVN content of both oat varieties reached a maximum on the fifth day of germination (153.51 ± 4.08 and 126.30 ± 3.33 µg/g for the Zaohua and Bayou oats, respectively). Furthermore, this study investigated the antiallergic and antioxidant activities of the germinated oats via hyaluronidase inhibition and 2,2-diphenyl-1-picrylhydrazyl (DPPH)-scavenging assays. The antiallergic and DPPH-scavenging abilities of the ungerminated forms of both oat varieties were weaker. However, on the fifth day of germination, the inhibition rate of anthranilamide hyaluronidase reached 72.7% and 67.3% for the Zaohua and Bayou oat varieties, respectively. The antiallergic abilities of the oats increased significantly on the fifth day of germination in terms of their antiallergic capacities and DPPH clearance (82.67% and 77.64% for the Zaohua and Bayou oats, respectively), and the two indicators exhibited similar trends. These findings demonstrated that AVNs exhibit good antisensitivity and antioxidation properties, and the antisensitivity effect correlated positively with the AVN content.
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Antialérgicos , Avena , Antialérgicos/análisis , Antioxidantes/química , Avena/química , Grano Comestible/química , Germinación , Hialuronoglucosaminidasa , ortoaminobenzoatos/químicaRESUMEN
Background: Nonalcoholic fatty liver disease (NAFLD) is the most common metabolic disease and is intertwined with cardiovascular disorders and diabetes. Chaihu Shugan powder (CSP) is a traditional Chinese medicine with a significant therapeutic effect on metabolic diseases, such as NAFLD. However, its pharmacological mechanisms remain to be elucidated. Methods: The main compounds of CSP were measured using LC-MS/MS. A network pharmacology study was conducted on CSP. Its potential active ingredients were selected according to oral bioavailability, drug similarity indices, and phytochemical analysis. After obtaining the intersected genes between drug targets and disease-related targets, the component-disease-target network and protein-protein interaction analysis were visualized in Cytoscape. GO and KEGG enrichment analyses were performed using the Metascape database. Six-week-old male C57BL/6 mice fed a high-fat high-fructose diet for 16 weeks plus chronic immobilization stress for 2 weeks, an in vivo model, were administered CSP or saline intragastrically. Liver histology, triglyceride and cholesterol levels, ELISA, and RT-PCR were used to assess hepatic inflammation and steatosis. Immunohistochemistry and western blotting were performed to assess protein levels. Results: A total of 130 potential target genes in CSP that act on NAFLD were identified through network pharmacology assays, including tumor necrosis factor (TNF), interleukin-6 (IL6), interleukin-1ß (IL-1ß), and peroxisome proliferator-activated receptor γ (PPARG). KEGG enrichment analysis showed that the main pathways were involved in inflammatory pathways, such as the TNF and NF-κB signaling pathways, and metabolism-related pathways, such as the MAPK, HIF-1, FoxO, and AMPK signaling pathways. The results in vivo showed that CSP ameliorated liver inflammation and inhibited hepatic fatty acid synthesis in the hepatocyte steatosis model. More specifically, CSP therapy significantly inhibited the expression of tumor necrosis factor α (TNFα), accompanied by a decrease in TNF receptor 1 (TNFR1) and the ligand availability of TNFR1. Conclusion: Through the combination of network pharmacology and in vivo validation, this study elucidated the therapeutic effect of CSP on NAFLD, decreasing liver inflammation and inhibiting hepatic fatty acid synthesis. More specifically, the anti-inflammatory action of CSP was at least partially mediated by inhibiting the TNFα/TNFR1 signaling pathway.
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Background: Stable angina is a common condition with high morbidity and mortality rates. It has been reported that combining oral Chinese patent medicines (OCPMs) and Western medicine (WM) could potentially achieve a better effect than WM alone. However, the optimal OCPMs for stable angina remain controversial and merit further empirical research. Methods: PubMed, Embase, Web of Science, Cochrane Library, Ovid-Medline, Clinical Trials.gov, China National Knowledge Infrastructure, Wanfang Database, Weipu Journal Database, and Chinese Biomedical Literature Database were all searched from inception to 13 March 2022. We employed Version 2 of the Cochrane risk-of-bias tool (ROB2) to assess the overall quality of the selected studies. We also used R 4.1.2 and STATA 14.0 software applications to perform network meta-analysis, followed by sensitivity and subgroup analysis. Results: A total of 179 randomized controlled trials with 16,789 patients were included. The selected trials were all assessed as some concerns. OCPMs combined with WM had a better treatment effect than WM alone. In terms of the effective clinical rate, a significant increase was detected for Qishen Yiqi dripping pill (QSYQ)+WM as compared with Shensong Yangxin capsule (SSYX)+WM, Shexiang Baoxin pill (SXBX)+WM, Tongxinluo capsule (TXL)+WM, Xuefu Zhuyu capsule (XFZY)+WM, Qiliqiangxin capsule (QLQX)+WM, Naoxintong capsule (NXT)+WM, Fufang Danshen dripping pill (FFDS)+WM, and Danlou tablet (DL)+WM. QSYQ + WM had the highest-ranking probability (98.12%). Regarding the effective rate in ECG, QSYQ + WM was superior to SXBX + WM, TXL + WM, DL + WM, FFDS + WM, and NXT + WM. QSYQ + WM ranked first (94.21%). In terms of weekly frequency of angina, QLQX + WM obtained a better effect than FFDS + WM, Kuanxiong aerosol (KXQW)+WM, NXT + WM, QLQX + WM, SSYX + WM, SXBX + WM, and TXL + WM. QLQX + WM ranked first (100.00%). Regarding the duration of an angina attack, KXQW + WM was superior to SSYX + WM; KXQW + WM ranked first (95.71%). Adverting to weekly nitroglycerin usage, TXL + WM had the highest-ranking probability (82.12%). Referring to cardiovascular event rate, DL + WM had the highest effect (73.94%). Additionally, SSYX + WM had the lowest rate of adverse drug reactions (1.14%). Conclusion: OCPMs combined with WM had a higher efficacy. QSYQ + WM, QLQX + WM, KXQW + WM, TXL + WM, DL + WM, SSYX + WM, and SXBX + WM merit further investigation. SXBX + WM is presumably the optimal treatment prescription for both clinically effective and cardiovascular event rates. Further high-quality empirical research is needed to confirm the current results. Systematic Review Registration: URL = https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=316534, CRD 42022316534.
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Background: Acute tonsillitis has high morbidity. Chinese herbal injections (CHIs) were reported to be useful in treating acute tonsillitis and might reduce the probability of antibiotic resistance. Nevertheless, the optimal strategy for combining CHIs with western medicine (WM) to treat acute tonsillitis remains unclear. Methods: We retrieved data from the following databases with retrieval time from inception to 11 January 2022: PubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Wanfang Database, Weipu Journal Database, and Chinese Biomedical Literature Database. Version 2 of the Cochrane risk-of-bias tool (ROB2) was used for evaluating the quality of the included studies. R 4.1.2, STATA 14.0, and Python 3.10.4 were employed for network meta-analysis, with 5-dimensional K-means cluster analysis, meta-regression analyses, sensitivity analyses, and subgroup analyses. Results: A total of 110 randomized controlled trials including 12,152 patients were included. All the studies were rated as "high risk" and "some concerns". In terms of improving clinical effectiveness rate, Qingkailing injection + WM ranked ahead of other interventions (89.51%). Regarding reducing antipyretic time, Reduning injection + WM had the highest-ranking probability (68.48%). As for shortening sore throat relief time, Shuanghuanglian injection + WM ranked first (76.82%). Concerning shortening red and swollen tonsils relief time, Yanhuning injection + WM possessed the highest-ranking probability (89.17%). In terms of reducing tonsillar exudate relief time, Xuebijing injection + WM ranked ahead of the other interventions (94.82%). Additionally, the results of the cluster analysis suggested that Xuebijing injection + WM, Reduning injection + WM, and Yanhuning injection + WM were probably the best interventions. Furthermore, adverse drug reactions rate of Xuebijing injection + WM, Reduning injection + WM, Yanhuning injection + WM, Qingkailing injection + WM, and Shuanghuanglian injection + WM were individually 0.00%, 3.11%, 3.08%, 4.29%, and 4.62%. Conclusions: CHIs + WM have a better impact on patients with acute tonsillitis than WM alone. Xuebijing injection, Reduning injection, and Yanhuning injection might have potential advantages in treating the disease. Concerning adverse drug reactions, Xuebijing injection is presumably the optimal CHI. More high-quality studies are needed to further confirm our findings. Systematic Review Registration: CRD42022303243; URL= https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=303243.
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Shenmai injection (SMI) is a patented traditional Chinese medicine that is extracted from Panax ginseng and Ophiopogon japonicus and is commonly used to treat cardiovascular diseases and tumors. The O. japonicus extract Ophiopogonin D' (OPD') is highly cardiotoxic. Mitochondria are central to OPD'-induced cardiotoxicity, although the precise mechanisms remain unclear. Excessive mitophagy activation and mitochondrial dysfunction lead to apoptosis, and the PTEN-induced kinase 1(PINK1)/Parkin pathway is critical in regulating mitophagy and mitochondrial function. We investigated the role of the PINK1/Parkin pathway in OPD'-induced mitochondrial damage and cardiotoxicity in AC16 cells. Concentrations of 2 µM OPD' and above inhibited cardiomyocyte viability and increased lactate dehydrogenase (LDH) release in a concentration- and time-dependent manner. OPD' was toxic to cells and mitochondria and increased the rate of apoptosis, triggering pyknosis, decreasing mitochondrial membrane potential (MMP), and decreasing the protein expression of the biogenesis regulator peroxisome proliferator-activated receptor γ coactivator-1 alpha (PGC-1α). The increased ratio of microtubule-associated proteins 1 A/1B light chain 3B (LC3-II/LC3-I) in mitochondria indicated that OPD' induced mitophagy. OPD' significantly induced oxidative stress and apoptosis, including increased reactive oxygen species (ROS) generation and decreased nuclear factor erythroid-2 related factor 2 (Nrf2), heme oxygenase-1(HO-1), and B-cell lymphoma 2 (Bcl-2) protein expression. OPD' activated the PINK1/Parkin pathway and promoted PINK1/Parkin translocation to mitochondria. Inhibiting mitophagy attenuated OPD'-induced PINK1/Parkin pathway activation and preserved mitochondrial biogenesis, consequently mitigating OPD'-induced mitochondrial dysfunction and apoptosis. These findings suggest that OPD'-induced cardiomyocyte mitophagy and mitochondrial damage are at least partially mediated by dysregulation of the PINK1/Parkin pathway.
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Cardiotoxicidad , Mitofagia , Humanos , Proteínas Quinasas/metabolismo , Saponinas , Transducción de Señal , Espirostanos , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
OBJECTIVE: The aim of this study was to investigate the status of self-efficacy, resilience, personality traits, and job burnout of grassroots civil servants, and their relationship. METHODS: Grassroots civil servants were randomly selected, and questionnaire survey method was adopted. RESULTS: Civil servants with characteristics such as age, marital status, education level, and length of service were more prone to job burnout. Self-efficacy, resilience, and personality traits were important factors influencing job burnout of grassroots civil servants. Neuroticism played a regulating role in the relationship between self-efficacy and mental resilience. The increase of neuroticism score led to increasing mediation of self-efficacy on job burnout through decreased mental resilience. CONCLUSIONS: Higher levels of self-efficacy and mental resilience may reduce job burnout. Higher levels of neuroticism have a negative effect on the moderating role of self-efficacy on job burnout through psychological resilience.
Asunto(s)
Agotamiento Profesional , Resiliencia Psicológica , Agotamiento Profesional/psicología , Humanos , Satisfacción en el Trabajo , Neuroticismo , Personalidad , Autoeficacia , Encuestas y CuestionariosRESUMEN
Dietary supplementation with mung bean peptides (MBPs) has several health benefits. However, the effect of MBPs on prediabetes and gut microbiota imbalance caused by a high-fat diet (HFD) has not been thoroughly studied. In this study, dietary supplementation with MBPs for 5 weeks significantly reduced HFD-induced body weight gain, hyperglycaemia, hyperlipidaemia, insulin resistance, inflammation, and oxidative stress and alleviated liver and kidney damage in mice. In addition, it significantly reversed the HFD-induced gut microbiota imbalance, increased the gut microbial diversity, and decreased the abundance of Firmicutes and Bacteroidetes in prediabetic mice. Furthermore, we identified Lachnospiraceae_NK4A136 and Lactobacillus as important eubacteria with the potential to alleviate the clinical symptoms of prediabetes. According to PICRUSt2 analysis, the changes in intestinal microflora induced by MBPs diet intervention may be related to the downregulation of expression of genes such as rocR, lysX1, and grdA and regulation of seven pathways, including pyruvate, succinic acid, and butyric acid. Moreover, 17 genera with significantly altered levels in the intestine of HFD-fed mice, including Akkermansia, Roseburia, and Ruminiclostridium, were significantly correlated with 26 important differential metabolites, such as D-glutathione, anti-oleic acid, and cucurbitacin. Overall, these results show that MBPs diet intervention plays a key role in the management of HFD-induced prediabetes.