Whole-genome sequencing-based analysis of antimicrobial resistance, virulence factors, and genetic diversity in Yersinia isolated in Wenzhou, China 2020.

Yersinia spp. vary significantly in their ability to cause diseases that threaten public health. Their pathogenicity is frequently associated with increasing antimicrobial resistance (AMR) and various virulence factors. The aim of the study was to investigate the AMR genes, virulence factors, and genetic diversity of Yersinia strains isolated from meats and fish in Wenzhou in 2020 by using whole-genome sequencing (WGS). A total of 50 isolates were collected. The phylogenetic relationships among the Yersinia species were also analyzed using multilocus sequence typing (MLST), core genome multi-locus sequence typing (cgMLST), and single nucleotide polymorphism (SNP) analysis. According to the results, all the strains could be classified into five species, with most isolated from beef, followed by poultry, pork, and fish. AMR genes were identified in 23 strains. And the qnrD1 genes were all located in the Col3M plasmid. Virulence genes, such as yaxA, ystB, pla, and yplA, were also found in the 15 Y. enterocolitica strains. And this study also found the presence of icm/dot type IVB-related genes in one Yersinia massiliensis isolate. MLST analysis identified 43 sequence types (STs), 19 of which were newly detected in Yersinia. Moreover, cgMLST analysis revealed that no dense genotype clusters were formed (cgMLST 5341, 5344, 5346-5350, 5353-5390). Instead, the strains appeared to be dispersed over large distances, except when multiple isolates shared the same ST. Isolates Y4 and Y26 were closely related to strains originating from South Korea and Denmark. This study showed considerable diversity in Yersinia spp. isolated from local areas (Wenzhou City). The data generated in our study may enrich the molecular traceability database of Yersinia and provide a basis for the development of more effective antipathogen control strategies.

Dexmedetomidine alleviates pulmonary fibrosis through the ADORA2B-Mediated MAPK signaling pathway.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronically progressive fibrotic pulmonary disease characterized by an uncertain etiology, a poor prognosis, and a paucity of efficacious treatment options. Dexmedetomidine (Dex), an anesthetic-sparing alpha-2 adrenoceptor (α2AR) agonist, plays a crucial role in organ injury and fibrosis. However, the underlying mechanisms of IPF remain unknown. METHODS: In our study, the role of Dex in murine pulmonary fibrosis models was determined by Dex injection intraperitoneally in vivo. Fibroblast activation and myofibroblast differentiation were assessed after Dex treatment in vitro. The activation of MAPK pathway and the expression of Adenosine A2B receptor (ADORA2B) were examined in lung myofibroblasts. Moreover, the role of ADORA2B in Dex suppressing myofibroblast differentiation and pulmonary fibrosis was determined using the ADORA2B agonist BAY60-6583. RESULTS: The results revealed that Dex could inhibit Bleo-induced pulmonary fibrosis in mice. In vitro studies revealed that Dex suppressed TGF-ß-mediated MAPK pathway activation and myofibroblast differentiation. Furthermore, Dex inhibits myofibroblast differentiation and pulmonary fibrosis via downregulating ADORA2B expression. CONCLUSIONS: Our findings suggest Dex as a potential therapeutic agent for pulmonary fibrosis. Dex may alleviate lung fibrosis and myofibroblast differentiation through the ADORA2B-mediated MAPK signaling pathway.

Protective effect and mechanism of styrax on ischemic stroke rats: metabonomic insights by UPLC-Q/TOF-MS analysis.

CONTEXT: Styrax is used for prevention and treatment of cerebrovascular diseases. However, the underlying mechanism remains unclear. OBJECTIVE: To elucidate styrax's anti-ischemic stroke protective effects and underlying mechanisms. MATERIALS AND METHODS: An ischemic-stroke rat model was established based on middle cerebral artery occlusion (MCAO). Sprague-Dawley rats were randomly assigned to the following groups (n = 10) and administered intragastrically once a day for 7 consecutive days: sham, model, nimodipine (24 mg/kg), styrax-L (0.1 g/kg), styrax-M (0.2 g/kg) and styrax-H (0.4 g/kg). Neurological function, biochemical assessment, and ultra-performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS)-based serum metabonomics were used to elucidate styrax's cerebral protective effects and mechanisms. Pearson correlation and western blot analyses were performed to verify. RESULTS: The addition of 0.4 g/kg styrax significantly reduced cerebral infarct volume and neurobehavioral abnormality score. Different doses of styrax also decrease MDA, TNF-α, IL-6, and IL-1ß, and increase SOD and GSH-Px in ischemic-stroke rats (p < 0.05; MDA, p < 0.05 only at 0.4 g/kg dose). Biochemical indicators and metabolic-profile analyses (PCA, PLS-DA, and OPLS-DA) also supported styrax's protective effects. Endogenous metabolites (22) were identified in ischemic-stroke rats, and these perturbations were reversible via styrax intervention, which is predominantly involved in energy metabolism, glutathione and glutamine metabolism, and other metabolic processes. Additionally, styrax significantly upregulated phosphorylated AMP-activated protein kinase and glutaminase brain-tissue expression. CONCLUSION: Styrax treatment could ameliorate ischemic-stroke rats by intervening with energy metabolism and glutamine metabolism. This can help us understand the mechanism of styrax, inspiring more clinical application and promotion.

Asporin Promotes TGF-ß-induced Lung Myofibroblast Differentiation by Facilitating Rab11-Dependent Recycling of TßRI.

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic lung disease with high mortality and morbidity. ASPN (asporin), a member of the small leucine-rich proteoglycan family, plays crucial roles in tissue injury and regeneration. However, the precise pathophysiological role of ASPN and its molecular mechanisms in IPF remain unknown. We sought to investigate the role of ASPN during the development of pulmonary fibrosis and the therapeutic potential of targeting ASPN-related signaling pathways. In our study, three microarray datasets were downloaded from the Gene Expression Omnibus database, and differentially expressed genes were screened out by bioinformatic analysis. Hub genes were selected from the protein-protein interaction network. ASPN was examined in lung tissues from pulmonary fibrosis mouse models, and the role of ASPN in transforming growth factor (TGF)-ß/Smad signaling was determined by transfection with ASPN shRNA vectors in vitro. Biotinylation assays were conducted to measure plasma membrane TFG-ß receptor I (TßRI) and TßRI recycling after ASPN knockdown. The results showed ASPN expression was increased in the lungs of pulmonary fibrosis mouse models, and ASPN was primarily localized in α-SMA+ myofibroblasts. In vitro experiments proved that ASPN knockdown inhibited TGF-ß/Smad signaling and myofibroblast differentiation by regulating the stability of TßRI. Further molecular mechanisms revealed that ASPN knockdown inhibited TGF-ß/Smad signaling by suppressing recycling of TßRI to the cell surface in a Rab11-dependent manner and facilitated lysosome-mediated degradation of TßRI. In conclusion, our findings provide important evidence for the use of ASPN as a novel pharmacological target for treating pulmonary fibrosis.

Retaining mTeSR1 Medium during Hepatic Differentiation Facilitates Hepatocyte-Like Cell Survival by Decreasing Apoptosis.

BACKGROUND/AIMS: Hepatocyte-like cells derived from human pluripotent stem cells could be an important cell source for hepatocyte transplantation. The present study investigated the effect of retaining mTeSR1 medium during hepatic differentiation on hepatocyte-like cells in vitro. METHODS: Human embryonic stem cell line H1 were treated with activin A and bone morphogenetic protein 4 (BMP4) for definitive endoderm (DE) cell induction and subsequently treated with BMP2 and fibroblast growth factor 4 (FGF4) for early hepatic cell induction. Hepatocyte growth factor (HGF) and fibroblast growth factor (KGF) were added for early hepatic cell expansion and then mixed with oncostatin-M for maturation. During DE induction, 0%, 25%, 50% and 75% concentrations of mTeSR1 medium were separately added for early hepatic induction and expansion. For optimization, the expression levels of SRY-related HMG-box 17 (SOX17) and forkhead box A2 (FOXA2) at day 4, alpha fetoprotein (AFP) and hepatocyte nuclear factor 4α (HNF4α) at day 15, and albumin (ALB) at day 25 were quantified in differentiated cells by qRT-PCR. The ALB-positive cell proportion was measured by flow cytometry. Functional tests including ALB secretion and indocyanine green (ICG) angiography uptake and release by ELISA, urea production by urea assay kit, and glycogen storage ability by periodic acid Schif reaction (PAS) staining were performed in the differentiated cells. The induced pluripotent stem (iPS) cells were used to examine whether the optimized method was suitable for differentiating iPS cells. DE and hepatic markers were detected by immunostaining, and functional testing was performed as described above. Flow cytometry with an Annexin V-FITC apoptosis detection kit and fluorescence microscopy with Hoechst 33258 were used to analyze apoptosis in differentiated cells derived from H1 cells. RESULTS: All differentiated cells with retention of 0%, 25%, 50% and 75% mTeSR1 expressed SOX17, FOXA2, AFP, HNF4α, and ALB, while higher expression levels were observed in differentiated cells in the 0% and 25% groups. The flow cytometry results showed that the proportion of ALB-positive differentiated cells derived from H1 cells was higher in the 25% mTeSR1 group than in other groups. However, no significant difference in ALB secretion, urea production, ICG uptake and release and glycogen storage ability was detected between the 25% and 0% groups. The iPS cells could differentiate into hepatocyte-like cells with 25% mTeSR1 retention. The apoptosis ratio of differentiated cells was lower in the 25% mTeSR1 group than in the 0% mTeSR1 group. CONCLUSION: Retaining 25% mTeSR1 medium during hepatic differentiation has been proposed to increase the percentage of ALB-positive cells and cell survival by decreasing cell apoptosis.

Suppression of OGN in lung myofibroblasts attenuates pulmonary fibrosis by inhibiting integrin αv-mediated TGF-ß/Smad pathway activation.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) represents a severe and progressive manifestation of idiopathic interstitial pneumonia marked by an uncertain etiology along with an unfavorable prognosis. Osteoglycin (OGN), belonging to the small leucine-rich proteoglycans family, assumes pivotal functions in both tissue formation and damage response. However, the roles and potential mechanisms of OGN in the context of lung fibrosis remain unexplored. METHODS: The assessment of OGN expression levels in fibrotic lungs was conducted across various experimental lung fibrosis mouse models. To elucidate the effects of OGN on the differentiation of lung myofibroblasts, both OGN knockdown and OGN overexpression were employed in vitro. The expression of integrin αv, along with its colocalization with lysosomes and latency-associated peptide (LAP), was monitored in OGN-knockdown lung myofibroblasts. Furthermore, the role of OGN in lung fibrosis was investigated through OGN knockdown utilizing adeno-related virus serotype 6 (AAV6)-mediated delivery. RESULTS: OGN exhibited upregulation in both lungs and myofibroblasts across diverse lung fibrosis mouse models. And laboratory experiments in vitro demonstrated that OGN knockdown inhibited the TGF-ß/Smad signaling pathway in lung myofibroblasts. Conversely, OGN overexpression promoted TGF-ß/Smad pathway in these cells. Mechanistic insights revealed that OGN knockdown facilitated lysosome-mediated degradation of integrin αv while inhibiting its binding to latency-associated peptide (LAP). Remarkably, AAV6-targeted OGN knockdown ameliorated the extent of lung fibrosis in experimental mouse models. CONCLUSION: Our results indicate that inhibiting OGN signaling could serve as a promising therapeutic way for lung fibrosis.

Identification of diagnostic hub genes related to neutrophils and infiltrating immune cell alterations in idiopathic pulmonary fibrosis.

Background: There is still a lack of specific indicators to diagnose idiopathic pulmonary fibrosis (IPF). And the role of immune responses in IPF is elusive. In this study, we aimed to identify hub genes for diagnosing IPF and to explore the immune microenvironment in IPF. Methods: We identified differentially expressed genes (DEGs) between IPF and control lung samples using the GEO database. Combining LASSO regression and SVM-RFE machine learning algorithms, we identified hub genes. Their differential expression were further validated in bleomycin-induced pulmonary fibrosis model mice and a meta-GEO cohort consisting of five merged GEO datasets. Then, we used the hub genes to construct a diagnostic model. All GEO datasets met the inclusion criteria, and verification methods, including ROC curve analysis, calibration curve (CC) analysis, decision curve analysis (DCA) and clinical impact curve (CIC) analysis, were performed to validate the reliability of the model. Through the Cell Type Identification by Estimating Relative Subsets of RNA Transcripts algorithm (CIBERSORT), we analyzed the correlations between infiltrating immune cells and hub genes and the changes in diverse infiltrating immune cells in IPF. Results: A total of 412 DEGs were identified between IPF and healthy control samples, of which 283 were upregulated and 129 were downregulated. Through machine learning, three hub genes (ASPN, SFRP2, SLCO4A1) were screened. We confirmed their differential expression using pulmonary fibrosis model mice evaluated by qPCR, western blotting and immunofluorescence staining and analysis of the meta-GEO cohort. There was a strong correlation between the expression of the three hub genes and neutrophils. Then, we constructed a diagnostic model for diagnosing IPF. The areas under the curve were 1.000 and 0.962 for the training and validation cohorts, respectively. The analysis of other external validation cohorts, as well as the CC analysis, DCA, and CIC analysis, also demonstrated strong agreement. There was also a significant correlation between IPF and infiltrating immune cells. The frequencies of most infiltrating immune cells involved in activating adaptive immune responses were increased in IPF, and a majority of innate immune cells showed reduced frequencies. Conclusion: Our study demonstrated that three hub genes (ASPN, SFRP2, SLCO4A1) were associated with neutrophils, and the model constructed with these genes showed good diagnostic value in IPF. There was a significant correlation between IPF and infiltrating immune cells, indicating the potential role of immune regulation in the pathological process of IPF.

DACT2 protects against pulmonary fibrosis via suppressing glycolysis in lung myofibroblasts.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive fibrotic lung disease with poor prognosis and few treatment options. Dapper homolog 2 (DACT2), a member of the DACT gene family, plays crucial roles in tissue development and injury. However, its functions and molecular mechanisms in IPF remain largely unknown. We aimed to investigate the role of DACT2 in the development of pulmonary fibrosis and the therapeutic potential of targeting DACT2 related signaling pathways. METHODS: In our study, adeno-associated virus serotype 6 (AAV6)-mediated DACT2 overexpression was assessed in several mice models of experimental pulmonary fibrosis in vivo. The role of DACT2 in lung myofibroblast differentiation was determined by DACT2 overexpression in vitro. The glucose uptake, extracellular acidification rate, intracellular adenosine-triphosphate (ATP) level and lactate levels of myofibroblasts were detected after DACT2 overexpression. The LDHA degradation rate and colocalization with lysosomes were monitored as well. RESULTS: Intratracheal administration of AAV6-mediated DACT2 overexpression apparently attenuated pulmonary fibrosis in experimental pulmonary fibrosis models. In vitro experiments revealed that DACT2 inhibited TGF-ß-induced myofibroblast differentiation by promoting lysosome-mediated LDHA degradation and thus suppressing glycolysis in myofibroblasts. CONCLUSION: In conclusion, our findings support for DACT2 as a novel pharmacological target for pulmonary fibrosis treatments.

Tetrahydropalmatine: Orchestrating survival - Regulating autophagy and apoptosis via the PI3K/AKT/mTOR pathway in perforator flaps.

BACKGROUND: Introduced in clinical practice in 1989, perforator flaps are vital for tissue defect repair, but they are challenged by distal necrosis. Tetrahydropalmatine (THP) from celandine is renowned for its anti-inflammatory and analgesic effects. This study investigates THP's use in perforator flaps. METHODS: Thirty rats were divided into a control group and four THP concentration groups, while seventy-eight rats were categorized as control, THP, THP combined with rapamycin (RAP), and RAP alone. We created 11 cm by 2.5 cm multi-regional perforator flaps on rat backs, assessing survival blood flow and extracting skin flap tissue for autophagy, oxidative stress, apoptosis, and angiogenesis markers. RESULTS: The THP group exhibited significantly reduced distal necrosis, increased blood flow density, and survival area on the seventh day compared to controls. Immunohistochemistry and Western blot results demonstrated improved anti-oxidative stress and angiogenesis markers, along with decreased autophagy and apoptosis indicators. Combining THP with RAP diminished flap survival compared to THP alone. This was supported by protein expression changes in the PI3K-AKT-mTOR pathway. CONCLUSION: THP enhances flap survival by modulating autophagy, reducing tissue edema, promoting angiogenesis, and mitigating apoptosis and oxidative stress. THP offers a potential strategy for enhancing multi-regional perforator flap survival through the PI3K/AKT/mTOR pathway. These findings highlight THP's promise in combatting perforator flap necrosis, uncovering a novel mechanism for its impact on flap survival.

Does Public Health Influence Economic Performance? Investigating the Role of Governance and Greener Energies for the Case of China.

In the last few decades, the world has faced some natural issues, due to which economic growth faces a severe threat. Natural disasters like pandemic outbreaks and man-made disasters like pollution emissions are very frequent in the current times, which also influenced the economic growth, where the institutes could play a primary role in economic growth stimulation. This study aims to analyze the association of public health expenditures, institutional quality, renewable energy, and economic performance in China. This study uses quarterly data covering the period from 1996Q1 to 2020Q4 and employs various time-series estimating approaches. The Augmented Dickey-Fuller estimates asserted that all the variables are stationary at first difference. Also, the Bayer-Hanck combined cointegration validates that all the variables are cointegrated. Employing the three long-run estimators, i.e., Fully Modified Ordinary Least Square, Dynamic Ordinary Least Square, and canonical cointegrating regression, the results asserted public health expenditures and institutional quality (including government efficiency and political stability) significantly enhances economic performance in China. Whereas two indicators of corruption control and regulatory quality do not play any significant role in promoting the economic performance of China. On the contrary, renewable energy is found negatively associated with economic performance. Also, the Pair-wise Granger causality validates mixed causal associations between the study variables. As a developing and fossil energy-dependent economy, this study provides relevant policy implications for maintaining economic growth and rebalancing economic performance in China.

Mesenchymal stromal cells attenuate alveolar type 2 cells senescence through regulating NAMPT-mediated NAD metabolism.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive deadly fibrotic lung disease with high prevalence and mortality worldwide. The therapeutic potential of mesenchymal stem cells (MSCs) in pulmonary fibrosis may be attributed to the strong paracrine, anti-inflammatory, anti-apoptosis and immunoregulatory effects. However, the mechanisms underlying the therapeutic effects of MSCs in IPF, especially in terms of alveolar type 2 (AT2) cells senescence, are not well understood. The purpose of this study was to evaluate the role of MSCs in NAD metabolism and senescence of AT2 cells in vitro and in vivo. METHODS: MSCs were isolated from human bone marrow. The protective effects of MSCs injection in pulmonary fibrosis were assessed via bleomycin mouse models. The senescence of AT2 cells co-cultured with MSCs was evaluated by SA-ß-galactosidase assay, immunofluorescence staining and Western blotting. NAD+ level and NAMPT expression in AT2 cells affected by MSCs were determined in vitro and in vivo. FK866 and NAMPT shRNA vectors were used to determine the role of NAMPT in MSCs inhibiting AT2 cells senescence. RESULTS: We proved that MSCs attenuate bleomycin-induced pulmonary fibrosis in mice. Senescence of AT2 cells was alleviated in MSCs-treated pulmonary fibrosis mice and when co-cultured with MSCs in vitro. Mechanistic studies showed that NAD+ and NAMPT levels were rescued in AT2 cells co-cultured with MSCs and MSCs could suppress AT2 cells senescence mainly via suppressing lysosome-mediated NAMPT degradation. CONCLUSIONS: MSCs attenuate AT2 cells senescence by upregulating NAMPT expression and NAD+ levels, thus exerting protective effects in pulmonary fibrosis.

Specnuezhenide reduces carbon tetrachloride-induced liver injury in mice through inhibition of oxidative stress and hepatocyte apoptosis.

OBJECTIVES: This study aimed to investigate the hepatoprotective effects of specnuezhenide against carbon tetrachloride (CCl4)-induced liver injury in mice. METHODS: Male C57BL/6 mice were intraperitoneally injected with 10 ml/kg body weight of CCl4 (0.5% diluted in arachis oil) for acute liver injury after oral administration of specnuezhenide for 7 days. Twenty-four hours after the final CCl4 injection, mice were euthanized and plasma and liver samples were collected. KEY FINDINGS: The results showed that specnuezhenide markedly and dose-dependently reduced serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity and relative liver weight, as well as ameliorated histopathological damage caused by CCl4 and decreased malondialdehyde (MDA) levels, and increased the activity of antioxidant enzymes, superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). Moreover, specnuezhenide promoted the expression and nuclear translocation of the nuclear factor erythroid 2-related factor 2 (Nrf2) and increased the mRNA and protein expression of Nrf2 signalling-related genes heme oxygenase-1 (HO-1), glutamate-cysteine ligase catalytic subunit (GCLC) and NAD(P)H:quinone oxidoreductase 1 (NQO1). Finally, TUNEL staining and immunohistochemistry indicated that specnuezhenide prevented CCl4-induced hepatocytic apoptosis by up-regulating B-cell lymphoma 2 (Bcl-2) expression and downregulating Bcl-2-associated X (Bax) expression. CONCLUSIONS: Specnuezhenide reduced CCl4-induced liver injury in mice by inhibiting oxidative stress via activation of Nrf2 signalling and decreasing hepatocyte apoptosis.

Antagonistic and synergistic effects of warming and microplastics on microalgae: Case study of the red tide species Prorocentrum donghaiense.

Bibliometric network analysis has revealed that the widespread distribution of microplastics (MPs) has detrimental effects on marine organisms; however, the combined effects of MPs and climate change (e.g., warming) is not well understood. In this study, Prorocentrum donghaiense, a typical red tide species in the East China Sea, was exposed to different MP concentrations (0, 1, 5, and 10 mg L-1) and temperatures (16, 22, and 28 °C) for 7 days to investigate the combined effects of MPs and simulated ocean warming by measuring different physiological parameters, such as cell growth, pigment contents (chlorophyll a and carotenoid), relative electron transfer rate (rETR), reactive oxygen species (ROS), superoxide dismutase (SOD), malondialdehyde (MDA), and adenosine triphosphate (ATP). The results demonstrated that MPs significantly decreased cell growth, pigment contents, and rETRmax, but increased the MDA, ROS, and SOD levels for all MP treatments at low temperature (16 °C). However, high temperatures (22 and 28 °C) increased the pigment contents and rETRmax, but decreased the SOD and MDA levels. Positive and negative effects of high temperatures (22 or 28 °C) were observed at low (1 and 5 mg L-1) and high MP (10 mg L-1) concentrations, respectively, indicating the antagonistic and synergistic effects of combined warming and MP pollution. These results imply that the effects of MPs on microalgae will likely not be substantial in future warming scenarios if MP concentrations are controlled at a certain level. These findings expand the current knowledge of microalgae in response to increasing MP pollution in future warming scenarios.

Small-Molecule Modulated Affinity-Tunable Semisynthetic Protein Switches.

Engineered protein switches have been widely applied in cell-based protein sensors and point-of-care diagnosis for the rapid and simple analysis of a wide variety of proteins, metabolites, nucleic acids, and enzymatic activities. Currently, these protein switches are based on two main types of switching mechanisms to transduce the target binding event to a quantitative signal, through a change in the optical properties of fluorescent molecules and the activation of enzymatic activities. In this paper, we introduce a new affinity-tunable protein switch strategy in which the binding of a small-molecule target with the protein activates the streptavidin-biotin interaction to generate a readout signal. In the absence of a target, the biotinylated protein switch forms a closed conformation where the biotin is positioned in close proximity to the protein, imposing a large steric hindrance to prevent the effective binding with streptavidin. In the presence of the target molecule, this steric hindrance is removed, thereby exposing the biotin for streptavidin binding to produce strong fluorescent signals. With this modular sensing concept, various sulfonamide, methotrexate, and trimethoprim drugs can be selectively detected on the cell surface of native and genetically engineered cells using different fluorescent dyes and detection techniques.

Knowledge Mapping of the Links Between the Gut Microbiota and Heart Failure: A Scientometric Investigation (2006-2021).

Background: There is considerable research value and extensive application perspectives to explore the link between gut microbiota and heart failure. The purpose of this study is to provide an overview of overall characteristics, evolutionary pathways, frontier research hotspots, and future trends in this field. Methods: Research datasets were acquired from the Web of Science Core Collection (WoSCC) between January 1, 2006 and December 31, 2021. Three different analysis tools including one online platform, VOS viewer V1.6.17.0, and CiteSpace V5.8.R2 software were used in order to conduct collaboration network analysis, co-cited analysis, co-occurring analysis, and citation burst detection. Results: A total of 873 publications in the WoSCC database met the requirement. The overall characteristics analysis showed that a steady growth trend in the number of publications and citations, with the predominant literature type being articles and the most frequent subject category being cardiac cardiovascular systems. The United States was the most prolific country and the center of national collaboration. Cleveland Clinic and Nathalie M. Delzenne provided the leading influence with publications, the cooperation between the institutes and authors were relatively weak. Moreover, gut microbiota, heart failure, risk factor, obesity, and inflammation were the keywords that appeared more frequently in the clustering analysis of reference co-citation and keyword co-occurrence. Burst detection analysis of top keywords showed that trimethylamine N-oxide (TMAO), bile acid, blood pressure, hypertension, and fermentation were the new research foci on the association between gut microbiota and heart failure. Strategies to improve gut microbiota hold promise as a new approach to treat heart failure. Conclusion: The comprehensive bibliometric study indicates that the structured information may be helpful in understanding research trends in the link between gut microbiota and heart failure, and locating research hotspots and gaps in this domain, especially further advances in this field will lead to significant breakthroughs in the development of novel therapeutic tools for metabolic modulation of heart failure.

Psychometric Evaluation of the Fear of COVID-19 Scale Among Chinese Population.

Fear is a negative emotional reaction to or persistent worry over an imminent public health event like COVID-19. The COVID-Fear Scale was developed in many countries, but not in China. The current study aims to examine the psychometric properties of Chinese version of the Fear of COVID-19 Scale. Translation into Chinese and back-translation into English were conducted firstly. Item analysis and exploratory factor analysis were conducted in Sample 1, followed by validity tests in Sample 2. Likely, test-retest reliability was conducted in sample 3. A bifactor structure of Chinese version of FCV-19S with a general fear factor and two orthogonal group factors with fear thoughts and physical response was confirmed. Besides, it has good internal consistency reliability (α = .92), composite reliability (CR = .92), and validity correlation validity. The results of the present study confirmed that the Chinese version of FCV-19S has good psychometric properties in the Chinese communities. Supplementary Information: The online version contains supplementary material available at 10.1007/s11469-020-00441-7.

Melatonin ameliorates myocardial injury by reducing apoptosis and autophagy of cardiomyocytes in a rat cardiopulmonary bypass model.

BACKGROUND: Myocardial injury is a frequent complication after cardiac surgery with cardiopulmonary bypass (CPB). This study aimed to test the hypothesis that melatonin could attenuate myocardial injury in a rat CPB model. METHODS: Eighteen male Sprague-Dawley rats were randomly divided into three groups, n = 6 for each group: the sham operation (SO) group, CPB group and melatonin group. Rats in the SO group underwent cannulation without CPB, rats in CPB group intraperitoneal injected an equal volume of vehicle daily for 7 days before being subjected to CPB and rats in melatonin group intraperitoneal injected 20 mg/kg of melatonin solution daily for 7 days before being subjected to CPB. After 120 min for CPB, the expression levels of plasma interleukin (IL) -6, IL-1ß, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), malondialdehyde (MDA), creatine kinase (CK) -MB and cardiac troponin T (cTnT) were measured. Reactive oxygen species (ROS) were detected by dihydroethidium (DHE). Apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining. Mitochondrial damage and autophagosomes were detected by electron microscopy. Apoptosis inducing factor (AIF) was detected by immunofluorescence. The expression of B cell lymphoma/leukemia2 associated X (Bax), B cell lymphoma/leukemia 2 (Bcl-2), cytochrome C (Cyto-C), cleaved caspase-9, AKT, p-AKT, signal transducer and activator of transcription 3 (STAT3), p-STAT3, LC3, P62, mechanistic target of rapamycin kinase (mTOR), p-mTOR and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were determined using western blotting. RESULTS: Melatonin significantly decreased the levels of IL-1ß, IL-6, MDA, CK-MB and cTnT and increased the levels of SOD and GSH-Px, all of which were altered by CPB. Melatonin reduced cardiomyocyte superoxide production, the apoptosis index and autophagy in cardiomyocytes induced by CPB. The AKT, STAT3 and mTOR signaling pathways were activated by melatonin during CPB. CONCLUSION: Melatonin may serve as a cardioprotective factor in CPB by inhibiting oxidative damage, apoptosis and autophagy. The AKT, STAT3 and mTOR signaling pathways were involved in this process.

Investigation of the Multi-Target Mechanism of Guanxin-Shutong Capsule in Cerebrovascular Diseases: A Systems Pharmacology and Experimental Assessment.

Guanxin-Shutong capsule (GXSTC), a combination of Mongolian medicines and traditional herbs, has been clinically proven to be effective in treating cerebrovascular diseases (CBVDs). However, the underlying pharmacological mechanisms of GXSTC in CBVDs remain largely unknown. In this study, a combination of systems pharmacology and experimental assessment approach was used to investigate the bioactive components, core targets, and possible mechanisms of GXSTC in the treatment of CBVDs. A total of 15 main components within GXSTC were identified using high-performance liquid chromatography coupled with diode array detector (HPLC-DAD) and a literature research. Fifty-five common genes were obtained by matching 252 potential genes of GXSTC with 462 CBVD-related genes. Seven core components in GXSTC and 12 core genes of GXSTC on CBVDs were further determined using the protein-protein interaction (PPI) and component-target-pathway (C-T-P) network analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis results predicted that the molecular mechanisms of GXSTC on CBVDs were mainly associated with the regulation of the vascular endothelial function, inflammatory response, and neuronal apoptosis. Molecular docking results suggested that almost all of core component-targets have an excellent binding activity (affinity < -5 kcal/mol). More importantly, in middle cerebral artery occlusion (MCAO) -injured rats, GXSTC significantly improved the neurological function, reduced the infarct volume, and decreased the percentage of impaired neurons in a dose-dependent manner. Western blotting results indicated that GXSTC markedly upregulated the expression of vascular endothelial growth factor A (VEGFA) and endothelial nitric oxide synthase (eNOS), while downregulating the expression of cyclooxygenase-2 (COX-2) and transcription factor AP-1 (c-Jun) in MCAO-injured rats. These findings confirmed our prediction that GXSTC exerts a multi-target synergetic mechanism in CBVDs by maintaining vascular endothelial function, inhibiting neuronal apoptosis and inflammatory processes. The results of this study may provide a theoretical basis for GXSTC research and the clinical application of GXSTC in CBVDs.

Corilagin ameliorates sleep deprivation-induced memory impairments by inhibiting NOX2 and activating Nrf2.

Sleep deprivation (SD) can induce cognitive and memory impairments. This impairment is in part due to oxidative stress damage in the hippocampus region of the brain. Corilagin (CL), a polyphenol belonging to the tannin family and extracted from Terminalia chebula and Phyllanthus emblica, shows strong antioxidant and neuroprotective effects. NF-E2-related factor (Nrf2)/heme oxygenase-1 (HO-1) and NADPH oxidase (NOX) are critical targets involved in cellular defense mechanisms against oxidative injury. Thus, we hypothesized that CL could be a preventive treatment for SD-induced memory impairments by inhibiting NOX2 and activating Nrf2. The results from behavioral tests showed that administration of CL resulted in significantly better performance compared to the SD mice. CL significantly normalized the elevated MDA level and the reduced activity of GPx and SOD (P <0.05, p<0.01) caused by SD. In hippocampal tissues, CL effectively activated Nrf2/HO-1 signaling and downregulated NOX2 protein expression compared with SD (P <0.05, P <0.01). Meanwhile, in vitro findings showed that knockdown of Nrf2 blocked the protective effect of CL versus Glu-induced toxicity, while the effect of CL was enhanced in NOX2 siRNA-transfected neurons. Overall, these findings provided evidence that CL ameliorates SD-induced memory impairments in mice by inhibiting NOX2 and activating Nrf2.

Resveratrol: Multi-Targets Mechanism on Neurodegenerative Diseases Based on Network Pharmacology.

Resveratrol is a natural polyphenol in lots of foods and traditional Chinese medicines, which has shown promising treatment for neurodegenerative diseases (NDs). However, the molecular mechanisms of its action have not been systematically studied yet. In order to elucidate the network pharmacological prospective effects of resveratrol on NDs, we assessed of pharmacokinetics (PK) properties of resveratrol, studied target prediction and network analysis, and discussed interacting pathways using a network pharmacology method. Main PK properties of resveratrol were acquired. A total of 13,612 genes related to NDs, and 138 overlapping genes were determined through matching the 175 potential targets of resveratrol with disease-associated genes. Gene Ontology (GO) function analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment were performed to obtain more in-depth understanding of resveratrol on NDs. Accordingly, nodes with high degrees were obtained according using a PPI network, and AKT1, TP53, IL6, CASP3, VEGFA, TNF, MYC, MAPK3, MAPK8, and ALB were identified as hub target genes, which showed better affinity with resveratrol in silico studies. In addition, our experimental results demonstrated that resveratrol markedly enhanced the decreased levels of Bcl-2 and significantly reduced the increased expression of Bax and Caspase-3 in hippocampal neurons induced by glutamate exposure. Western blot results confirmed that resveratrol inhibited glutamate-induced apoptosis of hippocampal neurons partly by regulating the PI3K/AKT/mTOR pathway. In conclusion, we found that resveratrol could target multiple pathways forming a systematic network with pharmacological effects.