Exploring the inflammation-related mechanisms of Lingguizhugan decoction on right ventricular remodeling secondary to pulmonary arterial hypertension based on integrated strategy using UPLC-HRMS, systems biology approach, and experimental validation.

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.

Mechanism of Zhenwu Decoction modulating TLR4/NF-κB/HIF-1α loop through miR-451 to delay renal fibrosis in type 2 CRS.

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.

Global research trends and emerging opportunities for integrin adhesion complexes in cardiac repair: a scientometric analysis.

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.

Effects of garlic supplementation on components of metabolic syndrome: a systematic review, meta-analysis, and meta-regression of randomized controlled trials.

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.

Renal fibrosis in type 2 cardiorenal syndrome: An update on mechanisms and therapeutic opportunities.

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.

Research trends and hotspots evolution of cardiac amyloidosis: a bibliometric analysis from 2000 to 2022.

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.