Proteomic Analysis of the Effect of Fuzheng Huayu Recipe on Fibrotic Liver in Rats

Hepatic fibrosis is a common pathological process of chronic liver diseases and would lead to cirrhosis, and Fuzheng Huayu (FZHY) is an effective Chinese herbal product against liver fibrosis. This study observes FZHY influence on proteome of fibrotic liver with differential proteomic approach and aims to understand FZHY multiple action mechanisms on liver fibrosis. The liver fibrosis models were induced with intraperitoneal injection of dimethylnitrosamine for 4 weeks in rats and divided into model control (model) and FZHY-treated (FZHY) groups, while normal rats were used as normal control (normal). After model establishment, rats in FZHY groups were administered 4 g/kg wt of FZHY for 4 weeks, and normal and model groups were given the same volume of saline. The liver proteins in the above 3 groups were separated by two-dimensional gel electrophoresis (2-DE), the differentially expressed spots were analyzed and compared between normal and model or model and FZHY groups, and then the proteins were identified with mass spectrum analysis and validated partially with western blot and real-time PCR. 1000~1200 spots were displayed on each 2D gel, and a total of 61 protein spots were found with significant intensity difference between normal control or FZHY and model control. 23 most obviously differential spots were excised, and in-gel digestion and 21 peptide mass fingerprints (PMF) were obtained with MALDI-TOF MS analysis, and 14 proteins were identified through protein database searching. Among 14 differentially expressed proteins, 8 proteins in normal and FZHY groups had the same tendency of differential expression compared with the ones in model group. And one of them, vimentin, was validated by western blot and real-time PCR analyses. Our study reveals 12 proteins responsible for fibrogenesis induced by DMN in rats, and among them, 8 proteins in fibrotic liver were regulated by FZHY, including aldehyde dehydrogenase, vimentin isoform (CRA_b), gamma-actin, vimentin, fructose-bisphosphate aldolase B, aldo-keto reductase, S-adenosylhomocysteine hydrolase isoform, and HSP90. It indicates that the action mechanism of FZHY antiliver fibrosis may be associated with modulation of proteins associated with metabolism and stress response, as well as myofibroblast activation. The study provides new insights and data for exploring the liver fibrogenesis pathophysiology and FZHY action mechanism against liver fibrosis

Defining Biological Networks for Noise Buffering and Signaling Sensitivity Using Approximate Bayesian Computation

Reliable information processing in cells requires high sensitivity to changes in the input signal but low sensitivity to random fluctuations in the transmitted signal. There are often many alternative biological circuits qualifying for this biological function. Distinguishing theses biological models and finding the most suitable one are essential, as such model ranking, by experimental evidence, will help to judge the support of the working hypotheses forming each model. Here, we employ the approximate Bayesian computation (ABC) method based on sequential Monte Carlo (SMC) to search for biological circuits that can maintain signaling sensitivity while minimizing noise propagation, focusing on cases where the noise is characterized by rapid fluctuations. By systematically analyzing three-component circuits, we rank these biological circuits and identify three-basic-biological-motif buffering noise while maintaining sensitivity to long-term changes in input signals. We discuss in detail a particular implementation in control of nutrient homeostasis in yeast. The principal component analysis of the posterior provides insight into the nature of the reaction between nodes

Mitochondrial EF4 links respiratory dysfunction and cytoplasmic translation in Caenorhabditis elegans

AbstractHow animals coordinate cellular bioenergetics in response to stress conditions is an essential question related to aging, obesity and cancer. Elongation factor 4 (EF4/LEPA) is a highly conserved protein that promotes protein synthesis under stress conditions, whereas its function in metazoans remains unknown. Here, we show that, in Caenorhabditis elegans, the mitochondria-localized CeEF4 (referred to as mtEF4) affects mitochondrial functions, especially at low temperature (15°C). At worms' optimum growing temperature (20°C), mtef4 deletion leads to self-brood size reduction, growth delay and mitochondrial dysfunction. Transcriptomic analyses show that mtef4 deletion induces retrograde pathways, including mitochondrial biogenesis and cytoplasmic translation reorganization. At low temperature (15°C), mtef4 deletion reduces mitochondrial translation and disrupts the assembly of respiratory chain supercomplexes containing complex IV. These observations are indicative of the important roles of mtEF4 in mitochondrial functions and adaptation to stressful conditions

Effect of Lifestyle Changes after Percutaneous Coronary Intervention on Revascularization

Objective. Whether optimal cardiovascular health metrics may reduce the risk of cardiovascular events in secondary prevention is uncertain. The study was conducted to evaluate the influence of lifestyle changes on clinical outcomes among the subjects underwent percutaneous coronary intervention (PCI). Methods. The study group consists of 17,099 consecutive PCI patients. We recorded data on subject lifestyle behavior changes after their procedure. Patients were categorized as ideal, intermediate, or poor CV health according to a modified Life’s Simple 7 score (on body mass, smoking, physical activity, diet, cholesterol, blood pressure, and glucose). Multivariable COX regression was used to evaluate the association between CV health and revascularization event. We also tested the impact of cumulative cardiovascular health score on reoccurrence of cardiovascular event. Results. During a 3-year median follow-up, 1,583 revascularization events were identified. The observed revascularization rate was 8.0%, 9.3%, and 10.6% in the group of patients with optimal (a modified Life’s Simple 7 score of 11–14), average (score = 9 or 10), or inadequate (less or equal than 8) CV health, respectively. After multivariable analysis, the adjusted hazard ratios were 0.83 (95% CI: 0.73–0.94) and 0.89 (95% CI: 0.79–0.99) for patients with optimal and average lifestyle changes comparing with the inadequate tertile ( for trend = 0.003). In addition, each unit increase in above metrics was associated with a decrease risk of revascularization (HR, 0.96; 95% confidence interval, 0.93–0.98; ). Conclusion. Ideal CV health related to lower incidence of cardiovascular events, even after the percutaneous coronary intervention. Revascularization can be reduced by lifestyle changes. The cardiovascular health metrics could be extrapolated to secondary prevention and need for further validation

The chinese herbal decoction danggui buxue tang inhibits angiogenesis in a rat model of liver fibrosis.

In this study, we investigated the anti-angiogenic effect of the Chinese herbal decoction Danggui Buxue Tang (DBT; Radix Astragali and Radix Angelicae sinensis in 5 : 1 ratio) in a rat model of liver fibrosis, in order to elucidate its mechanisms of action against liver fibrosis. Liver fibrosis was induced with CCl(4) and high-fat food for 6 weeks, and the rats were treated with oral doses of DBT (6 g raw herbs/kg/d) and N-Acetyl-L-cysteine (NAC; 0.1 g/kg/d). The results showed that both DBT and NAC attenuated liver fibrosis and neo-angiogenesis. Furthermore, DBT and NAC improved SOD activity but decreased MDA content and 8-OH-dG in fibrotic livers, with DBT being more effective than NAC. DBT decreased the expression of VEGF, Ang1 and TGF-β1 and their signaling mediators, whereas NAC had no effect on VEGF and VEGFR2 expression. Both DBT and NAC reduced HIF-1α gene and protein expression in fibrotic livers, with DBT being more effective. These data clearly demonstrate that the anti-fibrotic properties of DBT are related to its ability to inhibit angiogenesis and its anti-angiogenic mechanisms are associated with improving oxidative stress, regulating the expression and signaling of angiogenic factors, and especially modulating HIF-1α in fibrotic livers

Salvia Miltiorrhiza Ameliorates Liver Fibrosis by Activating Hepatic Natural Killer Cells in Vivo and in Vitro

Natural killer (NK) cells are known for their ability to kill activated hepatic stellate cells (HSCs), which has been confirmed both in patients and animal models. But the killing function is depressed in period of advanced liver injury. Salvia Miltiorrhiza (SM), a Chinese herbal medicine for invigorating blood circulation and eliminating stasis, is widely used to treat liver fibrosis in clinic. Nevertheless, the immunological mechanism remains unclearly. Here, we put forward the hypothesis that the anti-fibrotic effect of SM is concerned with boosting the activation of hepatic NK cells. Liver fibrosis was induced with carbon tetrachloride (CCl4) and effects of SM on NK cells and HSC (JS-1 cell line, HSC) were investigated in vivo and in vitro. Hepatic NK cells were isolated from C57BL/6 mice, and pre-incubated with SM before they were co-cultured with HSCs. We found that SM increased frequency of NK cells, enhanced activities of NKG2D and Nkp46 on NK cells and inhibited activation of HSCs in vivo and in vitro. SM could promote the activities of NK cells by increasing the expressions of NKG2D and IFN-γ before or after co-cultured with HSCs in vitro. Besides, SM could partially antagonize ASGM-1-induced NK cell depletion and enhance the cell activities to inhibit HSCs activation in vitro. Therefore, our work provided a new insight into the anti-fibrotic mechanism that SM could enhance the activities of NK cell to reduce liver fibrosis in vivo and in vitro

Bibliometric analysis of dental adhesives: research status and frontier development

Objective: A visual analysis of the literature in the field of dental adhesives is conducted in order to explore the current state of research, cutting-edge areas of interest, and future development trends in this domain.Methods: English literature related to dental adhesives published between 2000 and 2023 was searched in the Web of Science Core Collection database. The retrieved results were then imported into VOSviewer and CiteSpace software in plain text format. Various data, such as journal names, authors, institutions, countries, and keywords, were extracted for further bibliometric analysis.Results: A total of 19,403 publications were retrieved, featuring 42,365 authors, 7,359 institutions, 121 countries, and 1,523 journals. The annual publication and cumulative publication rates in this field are both on the rise. Among them, DENTAL MATERIALS is the journal with the highest publication rate, cumulative publication rate, and number of citations. Ozcan M is the author with the most publications and within the limitations of this study, is considered an influential author in the field (with the highest intermediary centrality score) and Meerbeek B is the author with the highest number of citations. UNIV SAO PAULO is the institution with the highest publication rate. The United States is the country with the highest publication rate and has the most collaborative partnerships with other countries. Collaboration between different authors, institutions, and countries in this field is indeed close, which has greatly contributed to the rapid development of dental adhesives. Current research focuses on various aspects such as the types of dental adhesives, adhesive strength, dental diseases, and clinical trials. Future research directions mainly concentrate on aspects such as nanoparticles, 3D printing, universal adhesives, antibacterial properties of adhesives, and adhesive strength.Conclusion: Within the defined scope of this study, we have conducted a quantitative and objective analysis of the current research status and emerging trends in dental adhesives. This analysis establishes a knowledge foundation and introduces novel perspectives for future in-depth investigations in this field

Biointerface topography regulates phenotypic switching and cell apoptosis in vascular smooth muscle cells

Background: In-stent restenosis (ISR) is a complex disease that occurs after coronary stenting procedures. The development of quality materials and improvement of our understanding on significant factors regulating ISR are essential for enhancing prognosis. Vascular smooth muscle cells (VSMCs) are the main constituent cells of blood vessel walls, and dysfunction of VMSCs can exacerbate ISR. Accordingly, in this study, we explored the influence of wrinkled material topography on the biological functions of VSMCs. Methods: Polydimethylsiloxane with a wrinkled topography was synthesized using elastomer base and crosslinking and observed by atomic force microscopy. VSMC proliferation, apoptosis, and morphology were determined by Cell Counting Kit-8 assays, fluorescence-assisted cell sorting, and phalloidin staining. α-Smooth muscle actin (α-SMA), major histocompatibility complex (MHC), and calponin 1 (CNN-1) expression levels were measured by quantitative real-time polymerase chain reaction and western blotting. Moreover, p53 and cleaved caspase-3 expression levels were evaluated by western blotting in VSMCs to assess apoptotic induction. Results: Surface topographies were not associated with a clear orientation or elongation of VSMCs. The number of cells was increased on wrinkled surfaces (0.7 μm in amplitude, and 3 μm in wavelength [W3]) compared with that on other surfaces, contributing to continuously increased cell proliferation. Moreover, interactions of VSMCs with the W3 surface suppressed phenotypic switching, resulting in ISR via regulation of α-SMA, calponin-1, and SM-MHC expression. The surface with an amplitude of 0.05 μm and a wavelength of 0.5 μm (W0.5) promoted apoptosis by inducing caspase 3 and p53 activities. Conclusion: Introduction of aligned topographies on biomaterial scaffolds could provide physical cues to modulate VSMC responses for engineering vascular constructs. Materials with wrinkled topographies could have applications in the development of stents to reduce ISR