HGF ameliorates cardiomyocyte apoptosis and inflammatory response in septic patients via the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway.

OBJECTIVE: This study aimed to analyze the impact of HGF on cardiomyocyte injury, apoptosis, and inflammatory response induced by lipopolysaccharide (LPS). METHODS: Enzyme-linked immunosorbent assay (ELISA) was utilized to quantify the levels of HGF, interleukin (IL)-6, IL-10, creatine phosphokinase-isoenzyme-MB (CK-MB), and cardiac troponin I (cTnI) in the samples. qPCR and Western blotting (WB) were employed to assess the mRNA and protein expressions of HGF, IL-10, IL-6, PI3K, AKT, p-PI3K, and p-AKT. RESULTS: The outcomes of the in vivo experiment revealed that serum levels of IL-6, IL-10, HGF and SOFA scores in the SC group were elevated in contrast to the non-SC group. The correlation analysis indicated a substantial and positive association among serum HGF, IL-6, and IL-10 levels and SOFA scores. Relative to IL-6, IL-10 levels, and SOFA scores, serum HGF demonstrated the highest diagnostic value for SC. Following LPS administration to stimulate H9c2 cells across various periods (0, 12, 24, 48, and 72 h), the levels of myocardial injury markers (CK-MB and cTnI) in the cell supernatants, intracellular inflammatory factors (mRNA and protein levels of IL-10 and IL-6), apoptosis and ROS levels, exhibited a gradual increase followed by a subsequent decline. Following the overexpression of HGF, there was an increase in cell viability, and a decrease in apoptosis, inflammation, oxidative stress injuries, and the protein phosphorylation expressions of PI3K and AKT.. After knockdown of HGF expression, the activity of LPS-induced H9c2 cells was further reduced, leading to increased cell injury, apoptosis, inflammation, oxidative stress,and the expression levels of PI3K and Akt protein phosphorylation were further elevated. CONCLUSION: HGF was associated with decreased LPS-induced H9c2 apoptosis and inflammation in H9c2 cells, alongside an improvement in cell viability, indicating potential cytoprotective effects. The mechanism underlying these impacts may be ascribed to the suppression of the PI3K/AKT signaling pathway.

Causal relationship between gut microbiota and puerperal sepsis: a 2-sample Mendelian randomization study.

Background: Some recent observational studies have shown that gut microbiota composition is associated with puerperal sepsis (PS) and no causal effect have been attributed to this. The aim of this study was to determine a causal association between gut microbiota and PS by using a two-sample Mendelian randomization (MR) analysis. Methods: This study performed MR analysis on the publicly accessible genome-wide association study (GWAS) summary level data in order to explore the causal effects between gut microbiota and PS. Gut microbiota GWAS (n = 18,340) were obtained from the MiBioGen study and GWAS-summary-level data for PS were obtained from the UK Biobank (PS, 3,940 cases; controls, 202,267 cases). Identification of single nucleotide polymorphisms associated with each feature were identified based on a significance threshold of p < 1.0 × 10-5. The inverse variance weighted (IVW) parameter was used as the primary method for MR and it was supplemented by other methods. Additionally, a set of sensitivity analytical methods, including the MR-Egger intercept, Mendelian randomized polymorphism residual and outlier, Cochran's Q and the leave-one-out tests were carried out to assess the robustness of our findings. Results: Our study found 3 species of gut microbiota, Lachnospiraceae FCS020, Lachnospiraceae NK4A136, and Ruminococcaceae NK4A214, to be associated with PS. The IVW method indicated an approximately 19% decreased risk of PS per standard deviation increase with Lachnospiraceae FCS020 (OR = 0.81; 95% CI 0.66-1.00, p = 0.047). A similar trend was also found with Lachnospiraceae NK4A136 (OR = 0.80; 95% CI 0.66-0.97, p = 0.024). However, Ruminococcaceae NK4A214 was positively associated with the risk of PS (OR = 1.33, 95% CI: 1.07-1.67, p = 0.011). Conclusion: This two-sample MR study firstly found suggestive evidence of beneficial and detrimental causal associations of gut microbiota on the risk of PS. This may provide valuable insights into the pathogenesis of microbiota-mediated PS and potential strategies for its prevention and treatment.

Liposomes in the cosmetics: present and outlook.

Liposomes are small spherical vesicles composed of phospholipid bilayers capable of encapsulating a variety of ingredients, including water- and oil-soluble compound, which are one of the most commonly used piggybacking and delivery techniques for many active ingredients and different compounds in biology, medicine and cosmetics. With the increasing number of active cosmetic ingredients, the concomitant challenge is to effectively protect, transport, and utilize these substances in a judicious manner. Many cosmetic ingredients are ineffective both topically and systemically when applied to the skin, thus changing the method of delivery and interaction with the skin of the active ingredients is a crucial step toward improving their effectiveness. Liposomes can improve the delivery of active ingredients to the skin, enhance their stability, and ultimately, improve the efficacy of cosmetics and and pharmaceuticals. In this review, we summarized the basic properties of liposomes and their recent advances of functionalities in cosmetics and and pharmaceuticals. Also, the current state of the art in the field is discussed and the prospects for future research areas are highlighted. We hope that this review will provide ideas and inspiration on the application and development of cosmetics and pharmaceuticals.

Superhydrophilic-superhydrophobic integrated system based on copper mesh for continuous and efficient oil-water separation.

In petroleum, petrochemicals, metallurgy, and chemical industries, a significant volume of oily wastewater is unavoidably generated throughout the production processes. This not only harms the environment but also brings about diverse adverse effects on social and economic progress. In this study, copper mesh separation membranes exhibiting superhydrophobicity and superhydrophilicity/underwater superoleophobicity were fabricated through in situ oxidation, chemical vapor deposition, and other physical and chemical modification techniques. Moreover, copper meshes possessing contrasting wetting properties were incorporated into a system combining superhydrophilicity and superhydrophobicity enabling the continuous and efficient separation of mixed oil-water liquids. The separation efficiency of both the superhydrophobic and superhydrophilic membranes surpassed 99.0% and remained above 97.0% after 15 days of continuous use, showcasing the remarkable effectiveness and durability of the integrated system design. This research presents a straightforward and cost-effective design approach for the large-scale treatment of oily wastewater in industrial settings, which is expected to have extensive applications in practical production.

A plasma proteomic approach in patients with heart failure after acute myocardial infarction: insights into the pathogenesis and progression of the disease.

Aims: The pathogenesis of disease progression targets for patients with heart failure after acute myocardial infarction was investigated by using plasma proteomics. Methods: The plasma proteomes of acute myocardial infarction patients with (MI-HF) and without (MI-WHF) heart failure were compared. Each group consisted of 10 patients who were matched for age and sex. The peptides were analyzed by 2-dimensional liquid chromatography coupled to tandem mass spectrometry in a high definition mode. Parallel reaction monitoring (PRM) verified the selected target proteins. Results: We identified and quantified 2,589 and 2,222 proteins, respectively, and found 117 differentially expressed proteins (DEPs) (≥1.5-fold), when the MI-HF and MI-WHF groups were compared. Of these 51 and 66 were significantly up-regulated and down-regulated, respectively. The significant DEPs was subjected to protein-protein interaction network analysis which revealed a central role of the NF-κB signaling pathway in the MI-HF patients. PRM verified that MB, DIAPH1, VNN1, GOT2, SLC4A1, CRP, CKM, SOD3, F7, DLD, PGAM2, GOT1, UBA7 and HYOU1 were 14 proteins which were highly expressed in MI-HF patients. Conclusions: These findings showed a group of proteins related to the NF-κB signaling pathway in the pathogenesis of patients with poor outcomes after experiencing MI-HF. These proteins may be useful candidate markers for the diagnosis of MI-HF as well as help to elucidate the pathophysiology of this major cause of mortality in older patients.

Efficacy of dexmedetomidine on myocardial ischemia/reperfusion injury in patients undergoing cardiac surgery with cardiopulmonary bypass: A protocol for systematic review and meta-analysis.

BACKGROUND: Cardiac surgery using cardiopulmonary bypass has been shown to cause reversible postischemic cardiac dysfunction and is associated with reperfusion injury and myocardial cell death. Therefore, it is very important to have a series of measures in place to reduce oxygen consumption and provide myocardial protection. We performed a protocol for systematic review and meta-analysis to evaluate the effect of dexmedetomidine administration on myocardial ischemia/reperfusion injury in patients undergoing cardiac surgery with cardiopulmonary bypass. METHODS: This review protocol is registered in the PROSPERO International Prospective Register of systematic reviews, registration number CRD42023386749. A literature search is performed in January 2023 without restriction to regions, publication types or languages. The primary sources were the electronic databases of PubMed, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure database, Chinese Biomedical Database, and Chinese Science and Technology Periodical database. Risk of bias will be assessed according to the Cochrane Risk of Bias Tool. The meta-analysis is performed using Reviewer Manager 5.4. RESULTS: The results of this meta-analysis will be submitted to a peer-reviewed journal for publication. CONCLUSION: This meta-analysis will evaluate the efficacy and safety of dexmedetomidine in patients undergoing cardiac surgery with cardiopulmonary bypass.

Glycosylation of the polyphenols from Resina draconis by glycosyltransferase YjiC1.

Resina Draconis (RD), also known as 'dragon's blood', contains a broad range of natural compounds, such as flavonoids, stilbenes and dihydrochalcones. It is clinically used to enhance blood circulation. However, the major components of RD suffer from relatively poor water solubility. Glycosylation is a critical determinant for modulating solubility and improving bioavailability and bioactivity of natural products. Herein, we report a novel method to efficiently synthesize glycosidic derivatives of the major polyphenols in RD using a microbial glycosyltransferase, i.e., YjiC1. Solubility test showed that the synthetic glycosidic derivatives displayed higher water solubility than the raw materials. This research sheds light on the structural modification of natural products for higher water solubility, which is important for innovative drug discovery.

Systematically investigating the fluorescent signal readout of CRISPR-Cas12a for highly sensitive SARS-CoV-2 detection.

The CRISPR/Cas system is widely used for molecular diagnostics after the discovery of trans-cleavage activity, especially now with the COVID-19 outbreak. However, the majority of contemporary trans-cleavage activity-based CRISPR/Cas biosensors exploited standard single-strand DNA (ssDNA) reporters, which were based on the FRET principle from pioneering research. An in-depth comparison and understanding of various fluorescent readout types are essential to facilitate the outstanding analytical performance of CRISPR probes. We investigated various types of fluorescent reporters of Cas12a comprehensively. Results show that trans-cleavage of Cas12a is not limited to ssDNA and dsDNA reporters, but can be extended to molecular beacons (MB). And MB reporters can achieve superior analytical performance compared with ssDNA and ds DNA reporters at the same conditions. Accordingly, we developed a highly-sensitive SARS-CoV-2 detection with the sensitivity as low as 100 fM were successfully achieved without amplification strategy. The model target of ORF1a could robustly identify the current widespread emerging SARS-CoV-2 variants. A real coronavirus GX/P2V instead of SARS-CoV-2 were chosen for practical application validation. And a minimum of 27 copies/mL was achieved successfully. This inspiration can also be applied to other Cas proteins with trans-cleavage activity, which provides new perspectives for simple, highly-sensitive and universal molecular diagnosis in various applications.

Fluorescence Signal-Readout of CRISPR/Cas Biosensors for Nucleic Acid Detection.

The CRISPR/Cas system is now being used extensively in nucleic acid detection applications, particularly after the trans-cleavage activity of several Cas effectors was found. A CRISPR/Cas system combined with multiple signal-readout techniques has been developed for various molecular diagnostics applications. Fluorescence is now a widely utilized dominant read-out technique in CRISPR biosensors. An in-depth understanding of various fluorescence readout types and variables affecting the fluorescence signals can facilitate better experimental designs to effectively improve the analytical performance. There are the following two commonly used types of CRISPR/Cas detection modes: the first is based on binding activity, such as Cas9 and dCas9; the second is based on cleavage activity, such as Cas12a, Cas12b, Cas13, and Cas14. In this review, fluorescence signal-readout strategies from the last 5 years based on the binding activity and cleavage activity of the CRISPR/Cas system with fundamentals and examples are fully discussed. A detailed comparison of the available fluorescent reporter sequences and design principles is summarized. Current challenges and further applications of CRISPR-based detection methods will be discussed according to the most recent developments.

Glycyrrhizic acid ameliorates myocardial ischemia-reperfusion injury in rats through inhibiting endoplasmic reticulum stress.

The purpose of this study was to investigate the role of glycyrrhizic acid (GA) in regulating myocardial ischemia-reperfusion injury (MIRI) in rats as well as the underlying mechanism. H9c2 cells were subjected to hypoxia/re-oxygenation (H/R) to mimic the MIRI in vitro, while a rat model of ischemia-reperfusion (I/R) was constructed by occlusion of the left anterior descending coronary artery for 0.5 h followed by 2 h of reperfusion. While flow cytometry and TUNEL assay were performed to analyze apoptosis in cells and myocardial tissue, echocardiography, hematoxylin and eosin staining, and Masson's trichrome staining were conducted to evaluate cardiac function and pathological changes, respectively. The levels of serum CK, CK-MB, LDH, AST, TNF-α, and IL-6 as well as the contents of MDA and SOD in tissues were measured by ELISA, while Western blot analysis was performed to detect the expression of endoplasmic reticulum stress (ERS)-related proteins. GA treatment significantly reduced apoptosis in H9c2 cells, while it alleviated left ventricular dysfunction, fibrosis and myocardial apoptosis, down-regulated the levels of CK, CK-MB, LDH, AST, TNF-α, IL-6, and MDA, and up-regulated SOD levels in I/R rats. Moreover, GA treatment led to a decrease in the expression of CHOP, GRP78, and p-PERK in both H/R cells and I/R rats. This study demonstrates that cardioprotective role of GA in MIRI may involve the attenuation of ERS-induced apoptosis and inflammation, potentially providing an alternative strategy for intervention of MIRI.

Multiomics Analysis of Transcriptome, Epigenome, and Genome Uncovers Putative Mechanisms for Dilated Cardiomyopathy.

OBJECTIVE: Multiple genes have been identified to cause dilated cardiomyopathy (DCM). Nevertheless, there is still a lack of comprehensive elucidation of the molecular characteristics for DCM. Herein, we aimed to uncover putative molecular features for DCM by multiomics analysis. METHODS: Differentially expressed genes (DEGs) were obtained from different RNA sequencing (RNA-seq) datasets of left ventricle samples from healthy donors and DCM patients. Furthermore, protein-protein interaction (PPI) analysis was then presented. Differentially methylated genes (DMGs) were identified between DCM and control samples. Following integration of DEGs and DMGs, differentially expressed and methylated genes were acquired and their biological functions were analyzed by the clusterProfiler package. Whole exome sequencing of blood samples from 69 DCM patients was constructed in our cohort, which was analyzed the maftools package. The expression of key mutated genes was verified by three independent datasets. RESULTS: 1407 common DEGs were identified for DCM after integration of the two RNA-seq datasets. A PPI network was constructed, composed of 171 up- and 136 downregulated genes. Four hub genes were identified for DCM, including C3 (degree = 24), GNB3 (degree = 23), QSOX1 (degree = 21), and APOB (degree = 17). Moreover, 285 hyper- and 321 hypomethylated genes were screened for DCM. After integration, 20 differentially expressed and methylated genes were identified, which were associated with cell differentiation and protein digestion and absorption. Among single-nucleotide variant (SNV), C>T was the most frequent mutation classification for DCM. MUC4 was the most frequent mutation gene which occupied 71% across 69 samples, followed by PHLDA1, AHNAK2, and MAML3. These mutated genes were confirmed to be differentially expressed between DCM and control samples. CONCLUSION: Our findings comprehensively analyzed molecular characteristics from the transcriptome, epigenome, and genome perspectives for DCM, which could provide practical implications for DCM.

Association between α1-antitrypsin and acute coronary syndrome.

α1-antitrypsin (AAT) is a protein released as part of the anti-inflammatory response. It regulates the activity of serine proteinases and has a crucial role in the pathogenesis of acute coronary syndrome (ACS). The present study aimed to examine its role in patients with ACS. The plasma samples of 117 patients were collected at the Cardiology Department of the Affiliated Hospital of Youjiang Medical University (Baise, China). These included 46 cases of ACS (who met the diagnostic criteria for ACS and had ≥50% luminal stenosis of any coronary vessel), 35 cases of stable angina (SA; with ≥50% luminal stenosis of any coronary vessel but in a stable condition) and 36 normal healthy controls (subjects with no luminal stenosis in their coronary arteries). Plasma AAT protein concentrations were measured by ELISA and clinical data were collected. The plasma levels of AAT protein in patients with ACS were lower than those in controls and cases of SA (P<0.05), and the levels tended to decrease with the number of coronary artery lesions involved. There were no significant associations of the expression of plasma AAT protein and the number of diseased vessels in patients or the degree of stenosis. There was no correlation between the plasma protein levels of AAT and Gensini scores of patients with ACS. In conclusion, the plasma AAT protein levels in patients with ACS may contribute to the occurrence and development of coronary artery disease.

An Efficient Strategy for the Chemo-Enzymatic Synthesis of Bufalin Glycosides with Improved Water Solubility and Inhibition against Na+ , K+ -ATPase.

In this study, bufalin was glycosylated by an efficient chemo-enzymatic strategy. Firstly, 2-chloro-4-nitrophenyl-1-O-ß-D-glucoside (sugar donors) was obtained by chemical synthesis. Then, the glycosylation of the bufalin was achieved with the synthesized sugar donor under the catalysis of two glycosyltransferases (Loki and ASP). Finally, two glycosides, i. e., bufalin-3-O-ß-D-glucopyranoside and bufalin-3-O-[ß-D-glucopyranosyl-(1→2)-ß-D-glucopyranoside)], were obtained by preparative HPLC. Compared to our previously reported sole chemical (total yield 10 % in four steps) or enzymatic methods (30 %), our combined chemo-enzymatic strategy in this article greatly improves the yields of monoglycoside (68 %) and diglycoside (21 %) and decreased the experimental cost (90 %). Furthermore, we tested the water solubility of these glycosides and found that the water solubilities of the two glycosides were 13.1 and 53.7 times of bufalin, respectively. In addition, the inhibitory activity of these glycosides against Na+ , K+ -ATPase were evaluated. The mono-glycosylated compound showed more potent activity than bufalin, while the diglycosylated compound was less potent.

Correlation between coronary stenosis and Toll-like receptors 2 and 4 levels in Chinese Zhuang patients with coronary heart disease.

The present study attempted to determine the correlation of the degree of coronary artery stenosis and Tolllike receptor 2/4 (TLR2/4) levels in Chinese Zhuang patients with coronary heart disease (CHD). A total of 466 Chinese patients from the Zhuang Ethnic population diagnosed with CHD at the Department of Cardiology the Affiliated Hospital of Youjiang Medical University between January 2016 and August 2017, together with 102 control patients, were recruited for the present study. The patients with CHD were divided into three groups depending on the number of diseased arteries. The patients with CHD were also classified according to their Gensini scores. Blood liver and renal function parameters, as well as blood sugar and lipid levels were measured. ELISA was used for TLR2/4 measurements. There were no significant differences with gender, age and body mass index between the CHD and control groups. The levels of TLR2/4 in the peripheral blood of the control and CHD groups were 2.34±0.85/5.08±2.41 and 5.22±3.16/9.33±4.92 ng/ml, respectively, and the differences were significant (P<0.001). Analysis of the three subgroups of vessel disease indicated that the expression of TLR2/4 was progressively higher with the increase in the number of affected vessels (P<0.01). There were also significant differences between the mild, moderate and severe stenosis groups (P<0.01). A positive linear correlation between TLR2/4 and the Gensini coronary artery score was identified (r=0.508 and 0.346, respectively; P<0.0001). In conclusion, the present study determined a positive correlation between the degree of coronary artery stenosis and the expression level of TLR2/4 in the serum of Chinese Zhuang patients with CHD. Serum TLR2/4 may be used to predict the severity of CHD.

Association of Toll-like receptor 4 polymorphisms with the risk of coronary artery disease in the ethnic Zhuang population of the Guangxi Province of China.

OBJECTIVES: Toll-like receptor 4 (TLR4) is known to be involved in the innate immunity and inflammatory responses that plays a crucial role in the pathogenesis of coronary artery disease (CAD). This study aimed to examine the potential relationship of TLR4 polymorphisms and serum TLR4 protein levels and the risk of CAD in the ethnic Zhuang population of China. METHODS: 1171 serum samples were collected from Zhuang patients, including 556 CAD cases (≥50% luminal stenosis of any coronary vessel) and 615 normal healthy controls (subjects with no luminal stenosis in coronary arteries). Detection of TLR4 polymorphisms was by single base extension polymerase chain reaction (Snapshot PCR) and DNA sequencing (rs11536879A/G and rs11536889G/C) gene sequence in all subjects. Serum TLR4 protein concentrations was measured by ELISA. RESULTS: There are significant differences in the allele and genotype frequencies of TLR4 gene rs11536889 between Chinese Zhuang CAD patients and controls, especially in the males. Male carriers of rs11536879 andrs11536889 variant alleles show an increased risk of CAD compared to non-carriers. Serum TLR4 protein levels of CAD patients are higher than controls and the levels tended to increase with the number of coronary artery lesions. Serum TLR4 protein levels of CAD patients showed no correlation with rs11536879 and rs11536889 polymorphisms. CONCLUSIONS: The rs11536879 and rs11536889 polymorphisms of TLR4 gene and serum TLR4 protein levels may contribute to the occurrence and development of CAD. However, the rs11536879 and rs11536889 polymorphisms have no significant effects on the expression of serum TLR4 protein in Zhuang patients with CAD.

Heterogeneous oxidative desulfurization of diesel fuel catalyzed by mesoporous polyoxometallate-based polymeric hybrid.

In this work, the simple preparation of novel polymer supported polyoxometallates (POMs) catalysts has been reported. Soluble task-specific cross-linked poly (ionic liquid) (PIL) was prepared with N,​N-​dimethyl-​dodecyl-​(4-​vinylbenzyl) ammonium chloride and divinylbenzene as co-monomers. The as-prepared cationic PILs were assembled with different commercial POMs to form the interlinked mesoporous catalysts, and the formation mechanism was provided. The catalytic oxidation activities of the catalysts were closely related to the formation pathway of their corresponding peroxide active species. The catalyst with H2W12O4210- as counterion, which exhibited the best activity in the oxidation of benzothiophene (BT) and dibenzothiophene (DBT) to sulfones in model oil with hydrogen peroxide (H2O2, 30wt%) as oxidant, was characterized by different techniques and systematically studied for its sulfur removal performance. As for the oxidative desulfurization of a real diesel, it was observed that almost all of the original sulfur compounds could be completely converted, and the catalyst could be reused for at least eight cycles without noticeable changes in both catalytic activity and chemical structure. In the end, a catalytic mechanism was put forward with the assistant of Raman analysis.