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Oxide thin films grown on metal surfaces have wide applications in catalysis and beyond owing to their unique surface structures compared to their bulk counterparts. Despite extensive studies, the atomic structures of copper surface oxides on Cu(111), commonly referred to as "44" and "29", have remained elusive. In this work, we demonstrated an approach for the structural determination of oxide surfaces using element-specific scanning tunneling microscopy (STM) imaging enhanced by functionalized tips. This approach enabled us to resolve the atomic structures of "44" and "29" surface oxides, which were further corroborated by noncontact atomic force microscopy (nc-AFM) measurements and Monte Carlo (MC) simulations. The stoichiometry of the "44" and "29" frameworks was identified as Cu23O16 and Cu16O11, respectively. Contrary to the conventional hypothesis, we observed ordered Cu vacancies within the "44" structure manifesting as peanut-shaped cavities in the hexagonal lattice. Similarly, a combination of Cu and O vacancies within the "29" structure leads to bean-shaped cavities within the pentagonal lattice. Our study has thus resolved the decades-long controversy on the atomic structures of "44" and "29" surface oxides, advancing our understanding of copper oxidation processes and introducing a robust framework for the analysis of complex oxide surfaces.
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BACKGROUND AND AIMS: The intratumoral microbiome has been reported to regulate the development and progression of cancers. We aimed to characterize intratumoral microbial heterogeneity (IMH) and establish microbiome-based molecular subtyping of HBV-related HCC to elucidate the correlation between IMH and HCC tumorigenesis. APPROACH AND RESULTS: A case-control study was designed to investigate microbial landscape and characteristic microbial signatures of HBV-related HCC tissues adopting metagenomics next-generation sequencing. Microbiome-based molecular subtyping of HCC tissues was established by nonmetric multidimensional scaling. The tumor immune microenvironment of 2 molecular subtypes was characterized by EPIC and CIBERSORT based on RNA-seq and verified by immunohistochemistry. The gene set variation analysis was adopted to explore the crosstalk between the immune and metabolism microenvironment. A prognosis-related gene risk signature between 2 subtypes was constructed by the weighted gene coexpression network analysis and the Cox regression analysis and then verified by the Kaplan-Meier survival curve.IMH demonstrated in HBV-related HCC tissues was comparably lower than that in chronic hepatitis tissues. Two microbiome-based HCC molecular subtypes, defined as bacteria- and virus-dominant subtypes, were established and significantly correlated with discrepant clinical-pathologic features. Higher infiltration of M2 macrophage was detected in the bacteria-dominant subtype with to the virus-dominant subtype, accompanied by multiple upregulated metabolism pathways. Furthermore, a 3-gene risk signature containing CSAG4 , PIP4P2 , and TOMM5 was filtered out, which could predict the clinical prognosis of HCC patients accurately using the Cancer Genome Atlas data. CONCLUSIONS: Microbiome-based molecular subtyping demonstrated IMH of HBV-related HCC was correlated with a disparity in clinical-pathologic features and tumor microenvironment (TME), which might be proposed as a biomarker for prognosis prediction of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Estudos de Casos e Controles , Vírus da Hepatite B/genética , Neoplasias Hepáticas/etiologia , Microambiente TumoralRESUMO
Superconducting nanowire single photon detectors (SNSPDs) have been extensively investigated due to their superior characteristics, including high system detection efficiency, low dark count rate and short recovery time. The polarization sensitivity introduced by the meandering-type superconductor nanowires is an intrinsic property of SNSPD, which is normally measured by sweeping hundreds of points on the Poincaré sphere to overcome the unknown birefringent problem of the SNSPD's delivery fiber. In this paper, we propose an alternative method to characterize the optical absorptance of SNSPDs, without sweeping hundreds of points on the Poincaré sphere. It is shown theoretically that measurements on the system detection efficiencies (SDEs) subject to cases of four specific photon polarization states are sufficient to reveal the two eigen-absorptances of the SNSPD. We validate the proposed method by comparing the measured detection spectra with the spectra attained from sweeping points on the Poincaré sphere and the simulated absorption spectra.
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Pathological cardiac remodeling normally involves changes in structure, function, and energy metabolism of the heart induced by cardiac injury or load, terminally leading to heart failure. Cardiac remodeling plays an essential role in the progression of cardiovascular disease, thus increasingly identified as an important therapeutic target for heart failure of all pathogenesis. Puerarin, as a natural isoflavone mainly from Pueraria lobata ï¼Willd.ï¼Ohwi, has been developed as injections, eye drops, microemulsions, etc., and is widely used in the clinical treatment of cardiovascular diseases in eastern Asia countries. In recent years, a growing number of studies have shown that puerarin significantly inhibits myocardial hypertrophic growth, myocyte death, fetal gene expression, fibroblast proliferation and activation, improves energy metabolism, promotes post-infarction angiogenesis, and suppresses inflammation and oxidative stress, consequently attenuating or preventing cardiac remodeling in response to multiple stimuli ( e.g., pressure overload, MIRI, MI, Iso, and Ang II stimulation). This review summarized the roles and underlying molecular mechanisms of puerarin in cardiac remodeling induced by diverse etiologies, aiming to help develop novel therapeutic strategies to prevent or reverse pathological ventricular remodeling.
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Doenças Cardiovasculares , Insuficiência Cardíaca , Isoflavonas , Pueraria , Doenças Cardiovasculares/tratamento farmacológico , Insuficiência Cardíaca/tratamento farmacológico , Humanos , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Pueraria/química , Remodelação VentricularRESUMO
The essential role of boronic esters in controlling both the direction and selectivity of chemical reactions as well as their significant function in catalytic activity have been demonstrated for industrially important processes. The specific interaction analyses of the monosaccharide GlcNH2 with boric acid are of interest since monosaccharides serve as model systems for the more sophisticated carbohydrate molecules. The interaction of GlcNH2 with boric acid was systematically investigated by numerous NMR techniques. A 1 : 1 chelate boron complex coordinated at the cis-1,2 position of GlcNH2 was identified as the major species in DMSO-d6 solution via1H and 13C INEPT DOSY NMR spectroscopy. This specific boron nitrogen coordination mechanism was further supported by the 1H-15N HSQC spectra. Variations in the spin-lattice relaxation times (T1) of the 13C1 nucleus also provided quantitative data regarding this non-covalent interactions. This is an application of 1H, 13C INEPT DOSY, 1H-15N HSQC, and relaxation methods to study such aggregations in solutions. These methods have potential applications in the characterization of reactive intermediates in biomass conversions.
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The objective of this systematic review and meta-analysis is to investigate the effect of high-intensity interval training (HIIT) on depressive symptoms, including an examination of its impact across different populations, intervention durations, and control groups through subgroup analysis. METHODS: A systematic literature search was conducted using the following databases: Cochrane, Embase, PubMed, Web of Science, China National Knowledge Infrastructure (CNKI), and Wanfang Data Knowledge Service Platform. The search covered the period from January 1, 2000, to December 31, 2022. RESULTS: The meta-analysis included 34 randomized controlled trials, involving a total of N = 1607 participants. HIIT had a small but significant effect on depressive symptoms compared to the control group [SMD = -0.40, 95%CI (-0.60, -0.20), I2 = 73%]. However, subgroup analyses revealed no moderating effect of health status or exercise duration on depressive symptoms. HIIT did not have a statistically significant effect on depressive symptoms when compared with other types of exercise [SMD = -0.15, 95% CI (-0.30, 0.01), I2 = 10%]. HIIT demonstrated a medium effect size in reducing depressive symptoms compared to a non-active control group [SMD = -0.53, 95% CI (-0.84, -0.21), I2 = 80%]. CONCLUSIONS: HIIT confers benefits in mitigating depressive symptoms. Compared to non-active control group, HIIT yields moderate improvements in depressive symptoms. We look forward to exploring more moderating effects in the future, such as HIIT modalities, frequency, and so on. In summation, these findings substantiate the use of HIIT as a means to alleviate symptoms of depression.
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Depressão , Treinamento Intervalado de Alta Intensidade , Humanos , Treinamento Intervalado de Alta Intensidade/métodos , Depressão/terapia , Depressão/psicologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Objective: Cardiac regenerative medicine has gained significant attention in recent years, and integrins are known to play a critical role in mediating cardiac development and repair, especially after an injury from the myocardial infarction (MI). Given the extensive research history and interdisciplinary nature of this field, a quantitative retrospective analysis and visualization of related topics is necessary. Materials and methods: We performed a scientometric analysis of published papers on cardiac integrin adhesion complexes (IACs), including analysis of annual publications, disciplinary evolution, keyword co-occurrence, and literature co-citation. Results: A total of 2,664 publications were finally included in the past 20 years. The United States is the largest contributor to the study and is leading this area of research globally. The journal Circulation Research attracts the largest number of high-quality publications. The study of IACs in cardiac repair/regenerative therapies involves multiple disciplines, particularly in materials science and developmental biology. Keywords of research frontiers were represented by Tenasin-C (2019-2023) and inflammation (2020-2023). Conclusion: Integrins are topics with ongoing enthusiasm in biological development and tissue regeneration. The rapidly emerging role of matricellular proteins and non-protein components of the extracellular matrix (ECM) in regulating matrix structure and function may be a further breakthrough point in the future; the emerging role of IACs and their downstream molecular signaling in cardiac repair are also of great interest, such as induction of cardiac proliferation, differentiation, maturation, and metabolism, fibroblast activation, and inflammatory modulation.
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This study aimed to identify active miRNA editing sites during adipose development in Ningxiang pigs and analyze their characteristics and functions. Based on small RNA-seq data from the subcutaneous adipose tissues of Ningxiang pigs at four stages-30 days (piglet), 90 days (nursery), 150 days (early fattening), and 210 days (late fattening)-we constructed a developmental map of miRNA editing in the adipose tissues of Ningxiang pigs. A total of 505 miRNA editing sites were identified using the revised pipeline, with C-to-U editing types being the most prevalent, followed by U-to-C, A-to-G, and G-to-U. Importantly, these four types of miRNA editing exhibited base preferences. The number of editing sites showed obvious differences among age groups, with the highest occurrence of miRNA editing events observed at 90 days of age and the lowest at 150 days of age. A total of nine miRNA editing sites were identified in the miRNA seed region, with significant differences in editing levels (p < 0.05) located in ssc-miR-23a, ssc-miR-27a, ssc-miR-30b-5p, ssc-miR-15a, ssc-miR-497, ssc-miR-15b, and ssc-miR-425-5p, respectively. Target gene prediction and KEGG enrichment analyses indicated that the editing of miR-497 might potentially regulate fat deposition by inhibiting adipose synthesis via influencing target binding. These results provide new insights into the regulatory mechanism of pig fat deposition.
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BACKGROUND: Type 2 cardiorenal syndrome (CRS) is a progressive renal insufficiency in patients with chronic heart failure, but its pathophysiology is still unclear. The Chinese medicine Zhenwu Decoction plays an important role in the prevention and treatment of 2-CRS, however, its mechanism of action remains unknown. PURPOSE: The aim of this study was to investigate whether the ameliorative effect of ZWD on 2-CRS renal fibrosis is related to the modulation of miR-451 expression and thus mediating the TLR4/NF-κB/HIF-1α loop. STUDY DESIGN AND METHODS: A type 2 CRS rat model was constructed using ligation of the left anterior descending branch of the coronary artery + 3/4 nephrectomy, and randomly divided into Control, Sham, Model, Captopril, ZWD-L, ZWD-M and ZWD-H groups.After 4 weeks of ZWD intervention, its effects on cardiac and renal functions of type 2 CRS rats were observed by hematuria and cardiac ultrasonography. Changes in kidney tissue morphology were observed by HE, Masson and PASM staining. The protein and mRNA expression of TLR4, NF-κB, HIF-1α and IκBα in kidney tissues were detected by immunohistochemistry and qPCR. Immunofluorescence was used to detect the protein expression of NF-κB and HIF-1α in renal tissues. Western blot and qPCR were used to detect the protein expression of MCP-1, ICAM-1, IL-1ß, IL-6, TGF-ß, α-SMA, FN, Smad2, Smad3, and E-cadherin in renal tissues. PCR was used to detect the protein expression of miR-451mRNA expression level in kidney tissues. RESULTS: In this study, we found that ZWD was able to reduce the expression of Scr, BUN, NT-proBNP, and 24-hour quantitative urine protein, elevate LVEF, FS, CO, and reduce the level of LVIDS in type 2 CRS rats, as well as attenuate renal interstitial fibrosis and improve tubular swelling. In addition, Zhenwu Decoction up-regulated the expression of miR-451 in renal tissues and inhibited the expression of TLR4, NF-κB, and HIF-1α proteins and genes, which in turn inhibited the expression of inflammatory factors and fibrosis-related factors. CONCLUSION: ZWD was able to up-regulate the expression of miR-451 in renal tissues, inhibit the TLR4/NF-κB/HIF-1α response loop, and then inhibit the expression of inflammatory factors and fibrosis-related factors, improve renal fibrosis, and delay the pathological process of type 2 CRS.
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Síndrome Cardiorrenal , Medicamentos de Ervas Chinesas , Fibrose , Subunidade alfa do Fator 1 Induzível por Hipóxia , Rim , MicroRNAs , NF-kappa B , Ratos Sprague-Dawley , Receptor 4 Toll-Like , Animais , Receptor 4 Toll-Like/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , NF-kappa B/metabolismo , MicroRNAs/metabolismo , MicroRNAs/genética , Masculino , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Rim/efeitos dos fármacos , Rim/patologia , Síndrome Cardiorrenal/tratamento farmacológico , Ratos , Modelos Animais de DoençasRESUMO
BACKGROUND: Pulmonary arterial hypertension (PAH) and the consequent right heart dysfunction persist with high morbidity and mortality, and the mechanisms and pharmacologic interventions for chronic right-sided heart failure (RHF) have not been adequately investigated. Research has shown that prolonged inflammation is critical in precipitating the progression of PAH-associated right heart pathology. Some research demonstrated that Lingguizhugan decoction (LGZGD), as a classical Chinese medicine formula, had beneficial effects in alleviating PAH and RHF, while its underlying mechanisms involved are not fully elucidated. PURPOSE: Based on that, this study aims to investigate the effects and underlying mechanisms of LGZGD on PAH-induced RHF. STUDY DESIGN: In this study, we identified the serum constituents and deciphered the potential anti-inflammatory mechanism and crucial components of LGZGD using combined approaches of UPLC-HRMS, transcriptomic analysis, and molecular docking techniques. Finally, we used in vivo experiments to verify the expression of key targets in the monocrotaline (MCT)-induced RHF model and the intervene effect of LGZGD. RESULTS: Integrated strategies based on UPLC-HRMS and systems biology approach combined with in vivo experimental validation showed that LGZGD could improve right heart fibrosis and dysfunction via regulating diverse inflammatory signaling pathways and the activity of immune cells, including chemokine family CCL2, CXCR4, leukocyte integrins family ITGAL, ITGB2, and M2 macrophage infiltration, as well as lipid peroxidation-associated HMOX1, NOX4, and 4-HNE. CONCLUSION: The present research demonstrated for the first time that LGZGD might improve PAH-induced RHF through multiple anti-inflammatory signaling and inhibition of ferroptosis, which could provide certain directions for future research in related fields.
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Medicamentos de Ervas Chinesas , Hipertensão Arterial Pulmonar , Biologia de Sistemas , Remodelação Ventricular , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Hipertensão Arterial Pulmonar/tratamento farmacológico , Masculino , Remodelação Ventricular/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Simulação de Acoplamento Molecular , Ratos Sprague-Dawley , Ratos , Insuficiência Cardíaca/tratamento farmacológico , Modelos Animais de Doenças , Cromatografia Líquida de Alta PressãoRESUMO
The COVID-19 pandemic and its social, economic, and health implications have generally reduced women's fertility intentions in different countries. In this article, we aimed to review studies of the impact of COVID-19 infection on women's fertility intentions and interventions to provide a theoretical basis and practical benchmark for the development of effective intervention strategies in China, which lifted its zero COVID system in early December 2022.
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COVID-19 , Intenção , Feminino , Humanos , Pandemias , Fertilidade , China , Política PúblicaRESUMO
In the last 20 years, the cardiorenal syndrome (CRS) field has received growing attention. There have been innovations in cardiorenal interaction patterns, biological markers and management of CRS, and even significant changes in its concept and the paradigm of CRS pathophysiology, which considerably increases the difficulties in understanding and in-depth study of this field. However, few study summarized the development process of CRS and critical issues. This review focuses on topical evolutions and emerging trends in CRS pathophysiology, diagnostic pathways, and treatment strategies. A quantitative retrospective analysis, visual review, and evaluation of 1452 articles published in the domain of CRS from 2003 to 2022 was conducted using a bibliometric analysis based on the classic CiteSpace and VOSviewer software rather than a general review, aiming to provide reasonable ideas and directions for future research on CRS.
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Síndrome Cardiorrenal , Humanos , Síndrome Cardiorrenal/epidemiologia , Síndrome Cardiorrenal/terapia , Estudos Retrospectivos , BibliometriaRESUMO
Rebleeding following endoscopic treatment in patients with cirrhosis is a serious life-threatening complication. In the present study, a novel, reliable and non-invasive score for prediction of rebleeding following endoscopic therapy for esophagogastric variceal bleeding (EGVB) was developed. The present retrospective study recruited cirrhotic patients with EGVB (n=596) who underwent endoscopic therapy. Patients hospitalized from January 2015 to January 2020 were grouped into a training (n=437) cohort to develop the new score and those hospitalized from February 2020 to February 2022 were grouped into a validation (n=159) cohort to validate the score. The international normalized ratio (INR) and albumin-bilirubin (ALBI) grade were used to develop the INR-ALBI (IALBI) score to predict risk of rebleeding. In the training cohort, the prognostic performance of the IALBI score and other ALBI-associated scores (modified ALBI, platelet-ALBI and ALBI-fibrosis-4) at 1, 3 and 12 months was assessed using receiver operating characteristic (ROC) curve and Kaplan-Meier analysis. At each time point, most areas under the ROC curve of IALBI were higher than those of other ALBI-associated scores, particularly for prediction of early rebleeding. At 1 month, the rebleeding rates of patients with IALBI grade 2 and 3 were ~10.0- and 19.5-times higher than those of patients with grade 1, respectively. The negative predictive value (NPV) of IALBI for the training and validation cohort at 1 month was 100.0 and 97.8%, respectively. For viral and non-viral patients in the training cohort, IALBI showed good predictive ability and NPV for early rebleeding. The IALBI grading system successfully assessed rebleeding, particularly early rebleeding, in cirrhotic patients with EGVB following endoscopic therapy IALBI grade 1, predicted low risk of rebleeding and may not require endoscopic treatment again in the short-term.
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Cardio-oncology has grown rapidly worldwide as an emerging interdisciplinary discipline over the past decade. In the present bibliometric review, we employed VOSviewer and Citespace software to describe the literature landscape concerning cardio-oncology from 2010 to 2022. As a result, a total of 1,194 relevant publications were identified in the Web of Science database with an increasing trend. The United States dominated the field during the research period, and Italy, England and Canada had emerged as significant contributors to the study. Ky. Bonnie, Herrmann. Joerg and Fradley. Michael G were the most productive researchers. JACC: CardioOncology was the journal dedicated to the discipline of cardio-oncology and had published the greatest number of papers. Vascular disease and atrial fibrillation have attracted much attention as the main cardiovascular burden. Immune checkpoint inhibitor-specific cardiovascular toxicity, biomarkers and imaging examination together with the prevention of cardio-oncology are potential research hotspots. Notably, basic research is lagging behind, for which more researches are needed to fill the gap. In conclusion, bibliometric analysis provided valuable information for the development of cardio-oncology, which is full of opportunities and challenges.
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Fibrilação Atrial , Neoplasias , Humanos , Neoplasias/terapia , Bibliometria , ItáliaRESUMO
Brackish water was an important alternative source of freshwater. Desalination using flow electrode capacitive deionization (FCDI) needs to explore the role of ion exchange membranes (IEM) of FCDI. In this study, brackish water was desalinated using FCDI, and anion exchange membranes with different characteristics were used in the FCDI cell to investigate their influence. The result showed that the membrane polymer matrix was the main influencing factor for ion transport. Ion exchange capacity (IEC) has a huge impact that low IEC made the various ion transport priority. Low IEC not only limits ion transport but also leads to ion leakage in seawater. Resistance had a significant blockage to the effect with weak intensity.
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Cloreto de Sódio , Purificação da Água , Ânions , Águas Salinas , Eletrodos , AdsorçãoRESUMO
In the new century, cardiac amyloidosis has received more attention from many countries and institutions, leading to innovations in the essence of the pathology, biological markers, noninvasive tests, and staging diagnoses and treatments for this disease. However, few reviews have summarized the research trends and hotspots in cardiac amyloidosis. Bibliometrics analysis is a statistically based approach to research that visualizes the contributions of academic institutions and changes in research hotspots. Therefore, in this paper, we used Citespace and VOSviewer software to conduct co-occurrence analysis and collaborative network analysis on the countries, institutions, and authors in the articles related to cardiac amyloidosis since the new century. And further find out burst keywords and references to obtain the research history, disciplinary development, and new hotspots and topics.
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Amiloidose , Humanos , Bibliometria , SoftwareRESUMO
Cardiorenal syndrome (CRS) is a state of coexisting heart failure and renal insufficiency in which acute or chronic dysfunction of the heart or kidney lead to acute or chronic dysfunction of the other organ.It was found that renal fibrosis is an important pathological process in the progression of type 2 CRS to end-stage renal disease, and progressive renal impairment accelerates the deterioration of cardiac function and significantly increases the hospitalization and mortality rates of patients. Previous studies have found that Hemodynamic Aiteration, RAAS Overactivation, SNS Dysfunction, Endothelial Dysfunction and Imbalance of natriuretic peptide system contribute to the development of renal disease in the decompensated phase of heart failure, but the exact mechanisms is not clear. Therefore, in this review, we focus on the molecular pathways involved in the development of renal fibrosis due to heart failure and identify the canonical and non-canonical TGF-ß signaling pathways and hypoxia-sensing pathways, oxidative stress, endoplasmic reticulum stress, pro-inflammatory cytokines and chemokines as important triggers and regulators of fibrosis development, and summarize the therapeutic approaches for the above signaling pathways, including SB-525334 Sfrp1, DKK1, IMC, rosarostat, 4-PBA, etc. In addition, some potential natural drugs for this disease are also summarized, including SQD4S2, Wogonin, Astragaloside, etc.
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Síndrome Cardiorrenal , Insuficiência Cardíaca , Humanos , Síndrome Cardiorrenal/metabolismo , Insuficiência Cardíaca/tratamento farmacológico , Rim/patologia , Coração , FibroseRESUMO
BACKGROUND: Garlic (Allium sativum), the underground bulb of the Allium genus, has been consumed on Earth for thousands of years. Many clinical trials of garlic supplementation on components of metabolic syndrome (MetS) have emerged in recent years, but there is no consensus on the effect. This meta-analysis aimed at systematically evaluating the effect of garlic supplementation on components of MetS. METHODS: In this meta-analysis, we searched Pubmed, Embase, Cochrane, Medline, Web of Science databases, and clinical trials online sites from inception to November 1, 2022, with language restrictions to English. We engaged participants > 18 years and eligible for the clinical diagnosis of MetS or those with metabolic disorders and garlic was the only intervention. Outcomes included waist circumference, and body mass index, triglycerides, total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, blood pressure, and fasting blood glucose. Meta-regression and subgroup analyses were conducted based on six covariates (total sample size, the mean age, the mean dose, the duration of intervention, the oral form of garlic, and the dietary intervention). RESULTS: Results from 19 RCTs were included engaging 999 participants. Compared to placebo, garlic significantly reduced TG [SMD (95%CI) = -0.66 (-1.23, -0.09)], TC [SMD (95%CI) = -0.43 (-0.86, -0.01)], LDL [SMD (95%CI) = -0.44(-0.88, -0.01)], DBP [SMD (95%CI) = -1.33 (-2.14, -0.53)], BMI [SMD (95%CI) = -1.10(-1.90, -0.20)], and WC [SMD (95%CI) = -0.78(-1.09, -0.47)]. Meta-regression showed age and sample size are potential effect modifiers. CONCLUSION: According to the results of meta-analysis, the modulatory effect of garlic on some MetS components is evident. More high-quality, large-scale RCTs are needed to confirm iat based on the high heterogeneity and potential publication bias of the current data. TRIAL REGISTRATION: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=373228 , ID: CRD42022373228.
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Produtos Biológicos , Alho , Síndrome Metabólica , Humanos , Síndrome Metabólica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Antioxidantes , HDL-Colesterol , Suplementos NutricionaisRESUMO
BACKGROUND: Atrial fibrillation (AF) is one of the most common arrhythmias encountered in clinical settings. Currently, the pathophysiology of AF remains unclear, which severely limits the effectiveness and safety of medical therapies. The Chinese herbal formula Qi-Po-Sheng-Mai Granule (QPSM) has been widely used in China to treat AF. However, its pharmacological and molecular mechanisms remain unknown. PURPOSE: The purpose of this study was to investigate the molecular mechanisms and potential targets of QPSM for AF. STUDY DESIGN AND METHODS: The AF model was induced by Ach (66 µg/ml) and CaCl2 (10 mg/kg), and the dose of 0.1 ml/100 g was injected into the tail vein for 5 weeks. QPSM was administered daily at doses of 4.42 and 8.84 g/kg, and amiodarone (0.18 g/kg) was used as the positive control. The effect of QPSM on AF was assessed by electrocardiogram, echocardiography, and histopathological analysis. Then, we employed network pharmacology with single nucleus RNA sequencing (snRNA-Seq) to investigate the molecular mechanisms and potential targets of QPSM for AF. Furthermore, high performance liquid chromatography (HPLC) method was used for component analysis of QPSM, and molecular docking was used to verify the potential targets. Using the IonOptix single cell contraction and ion synchronization test equipment, single myocyte length and calcium ion variations were observed in real time. The expression levels of calcium Transporter-related proteins were detected by western blot and immunohistochemistry. RESULTS: Based on an Ach-CaCl2-induced AF model, we found that QPSM treatment significantly reduced atrial electrical remodeling-related markers, such as AF inducibility and duration, and attenuated atrial dilation and fibrosis. Network pharmacology identified 52 active ingredients and 119 potential targets for QPSM in the treatment of AF, and 45 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were enriched, among which calcium pathway had the greatest impact. Using single nucleus sequencing (snRNA-seq), we identified cardiomyocytes as the most differentially expressed in response to drug treatment, with nine differentially expressed genes enriched in calcium signaling pathways. High performance liquid chromatography and molecular docking confirmed that the core components of QPSM strongly bind to the key factors in the calcium signaling pathway. Additional experiments have shown that QPSM increases calcium transients (CaT) and contractility in the individual cardiomyocyte. This was accomplished by increasing the expression of CACNA1C and SERCA2a and decreasing the expression of CAMK2B and NCX1. CONCLUSION: The present study has systematically elucidated the role of QPSM in maintaining calcium homeostasis in cardiomyocytes through the regulation of calcium transporters, which could lead to new drug development ideas for AF.