Ceramides and pro-inflammatory cytokines for the prediction of acute coronary syndrome: a multi-marker approach.

BACKGROUND: There is a growing body of evidence supporting the significant involvement of both ceramides and pro-inflammatory cytokines in the occurrence and progression of acute coronary syndrome (ACS). METHODS: This study encompassed 216 participants whose laboratory variables were analysed using standardised procedures. Parameters included baseline serum lipid markers, comprising total cholesterol, low-density lipoprotein-cholesterol, high-density lipoprotein-cholesterol, triglycerides (TGs), lipoprotein(a) (LPa), fasting blood glucose, B-natriuretic peptide and hypersensitive C-reactive protein. Liquid chromatography-tandem mass spectrometry measured the concentrations of plasma ceramides. Enzyme-linked immunosorbent assay quantified tumour necrosis factor-α (TNF-α), interleukin 6 (IL6) and IL8. The correlation between ceramides and inflammatory factors was determined through Pearson's correlation coefficient. Receiver operating characteristic (ROC) curve analysis and multivariate logistic regression evaluated the diagnostic potential of models incorporating traditional risk factors, ceramides and pro-inflammatory cytokines in ACS detection. RESULTS: Among the 216 participants, 138 (63.89%) were diagnosed with ACS. Univariate logistic regression analysis identified significant independent predictors of ACS, including age, gender, history of diabetes, smoking history, TGs, TNF-α, IL-6, ceramide (d18:1/16:0), ceramide (d18:1/18:0), ceramide (d18:1/24:0), ceramide (d18:1/20:0) and ceramide (d18:1/22:0). Multivariate logistic regression analysis revealed significant associations between gender, diabetes mellitus history, smoking history, LPa, IL-6, ceramide (d18:1/16:0) and ACS. Receiver operating characteristic analysis indicated that model 4, which integrated traditional risk factors, IL-6 and ceramide (d18:1/16:0), achieved the highest area under the curve (AUC) of 0.827 (95% CI 0.770-0.884), compared with model 3 (traditional risk factors and ceramide [d18:1/16:0]) with an AUC of 0.782 (95% CI 0.720-0.845) and model 2 (traditional risk factors and IL-6), with an AUC of 0.785 (95% CI 0.723-0.846) in ACS detection. CONCLUSIONS: In summary, incorporating the simultaneous measurement of traditional risk factors, pro-inflammatory cytokine IL-6 and ceramide (d18:1/16:0) can improve the diagnostic accuracy of ACS.

The Plasma Concentration of Ticagrelor and Aspirin as a Predictor of Bleeding Complications in Chinese Acute Coronary Syndrome Patients With Dual Antiplatelet Therapy: A Prospective Observational Study.

PURPOSE: This study evaluated the association among the plasma concentration of ticagrelor, ARC124910XX, aspirin, and salicylic acid with the risk of recent bleeding in patients with the acute coronary syndrome. To this end, we developed an accurate model to predict bleeding. METHODS: A total of 84 patients included in this study cohort between May 2021 and November 2021. The risk factors were identified by univariate and multivariate analyses, and statistically significant risk factors identified in the multivariate analysis were included in the nomogram. We used the calibration curve and the receiver operating characteristic curve to verify the accuracy of the prediction model. RESULTS: Multivariable logistic analysis showed that ticagrelor concentration (odds ratio [OR]: 2.47, 95% confidence interval [CI], 1.51-4.75, P = 0.002), ST-segment elevation acute myocardial infarction (OR: 32.2, 95% CI, 2.37-780, P = 0.016), and lipid-lowering drugs (OR: 11.52, 95% CI, 1.91-110, P = 0.015) were positively correlated with bleeding. However, angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker (OR: 0.04, 95% CI, 0.004-0.213, P < 0.001) was negatively correlated with bleeding. The receiver operating characteristic curve analysis showed that ticagrelor concentration and these factors together predict the occurrence of bleeding (area under receiver operating characteristic curve = 0.945, 95% CI, 0.896-0.994) and that ticagrelor concentration >694.90 ng/mL is the threshold of bleeding concentration (area under receiver operating characteristic curve = 0.696, 95% CI, 0.558-0.834). CONCLUSION: In patients with acute coronary syndrome treated with dual antiplatelet therapy, ticagrelor concentration >694.90 ng/mL was an independent risk factor for bleeding (OR: 2.47, 95% CI, 1.51-4.75, P = 0.002), but ARC124910XX and salicylic acid concentration did not affect bleeding risk ( P > 0.05).

Speckle-tracking echocardiography provides sensitive measurements of subtle early alterations associated with cardiac dysfunction in T2DM rats.

BACKGROUND: Diabetic cardiomyopathy results in cardiac structural and functional abnormalities. Previous studies have demonstrated that inhibiting the RhoA/ROCK signalling pathway increases the injury resistance of cardiomyocytes. The early detection of cardiac structural and functional alterations may facilitate an improved understanding of the pathophysiologic progress and guide therapy. This study aimed to identify the optimal diagnostic measures for the subtle early alterations of cardiac dysfunction in type 2 diabetes mellitus (T2DM) rats. METHODS: Twenty-four rat models were divided into four groups and received treatments for 4 weeks: the CON group (control rats), the DM group (T2DM rats), the DMF group (T2DM rats receiving fasudil) and the CONF group (control rats receiving fasudil) group. Left ventricular (LV) structure was quantified by histological staining and transmission electron microscopy. LV function and myocardial deformation were assessed by high-frequency echocardiography. RESULTS: Treatment with fasudil, a ROCK inhibitor, significantly protected against diabetes-induced myocardial hypertrophy, fibrosis and mitochondrial dysfunction. Impaired LV performance was found in T2DM rats, as evidenced by significant reductions in the ejection fraction (EF), fractional shortening (FS) and the mitral valve (MV) E/A ratio (which decreased 26%, 34% and 20%, respectively). Fasudil failed to improve the conventional ultrasonic parameters in T2DM rats, but the myocardial deformation measured by speckle-tracking echocardiography (STE) were significantly improved (global circumferential strain, GCS: P = 0.003; GCS rate, GCSR: P = 0.021). When receiver operating characteristic (ROC) curves were used in combination with linear regression analysis, STE parameters were found to be characterized by both optimal prediction of cardiac damage [AUC (95% CI): fractional area change, FAC: 0.927 (0.744, 0.993); GCS: 0.819 (0.610, 0.945); GCSR: 0.899 (0.707, 0.984)] and stronger correlations with cardiac fibrosis (FAC: r = -0.825; GCS: r = 0.772; GCSR: r = 0.829) than conventional parameters. CONCLUSION: The results suggest that STE parameters are more sensitive and specific than conventional parameters in predicting the subtle cardiac functional changes that occur in the early stage, providing new insight into the management of diabetic cardiomyopathy.

Short-term effects of levosimendan use for venoarterial extracorporeal membrane oxygenation: A systematic review and meta-analysis.

OBJECTIVE: Levosimendan has been demonstrated to reduce the incidence of cardiogenic shock and facilitate weaning from cardiopulmonary bypass. However, the beneficial effects of levosimendan treatment on hospital outcomes in patients receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) are uncertain. We performed a systematic review and meta-analysis to evaluate the short-term effects of levosimendan use for patients undergoing VA-ECMO. METHODS: We searched PubMed, Embase, and the Cochrane Library for English articles published from inception to July 15, 2021. Observational studies comparing levosimendan versus non- levosimendan for VA-ECMO were considered eligible for the current study. RESULTS: Nine observational studies with 1058 patients were included. In-hospital mortality was 46.3% in the levosimendan group as compared with 50.7% in the control group. Levosimendan significantly reduced in-hospital mortality in patients undergoing VA-ECMO compared with the control group (RR, 0.80; 95% CI, 0.67-0.95; p = 0.013). The incidence of weaning from VA-ECMO was 79.3% in the levosimendan group as compared with 63.4% in the control group. Levosimendan significantly increase the incidence of weaning from VA-ECMO in patients as compared with the control group (RR, 1.20; 95% CI, 1.07-1.34; p = 0.002). In the one-way sensitivity analysis for estimating the effect of each study on mortality or weaning from VA-ECMO, omission of each study did not make a significant difference. CONCLUSIONS: Our study indicates that levosimendan use significantly reduced in-hospital mortality and increase the incidence of weaning in patients undergoing VA-ECMO.

Neuregulin-4 attenuates diabetic cardiomyopathy by regulating autophagy via the AMPK/mTOR signalling pathway.

BACKGROUND: Diabetic cardiomyopathy is characterized by left ventricle dysfunction, cardiomyocyte apoptosis, and interstitial fibrosis and is a serious complication of diabetes mellitus (DM). Autophagy is a mechanism that is essential for maintaining normal heart morphology and function, and its dysregulation can produce pathological effects on diabetic hearts. Neuregulin-4 (Nrg4) is an adipokine that exerts protective effects against metabolic disorders and insulin resistance. The aim of this study was to explore whether Nrg4 could ameliorate DM-induced myocardial injury by regulating autophagy. METHODS: Four weeks after the establishment of a model of type 1 diabetes in mice, the mice received Nrg4 treatment (with or without an autophagy inhibitor) for another 4 weeks. The cardiac functions, histological structures and cardiomyocyte apoptosis were investigated. Autophagy-related protein levels along with related signalling pathways that regulate autophagy were evaluated. In addition, the effects of Nrg4 on autophagy were also determined in cultured primary cardiomyocytes. RESULTS: Nrg4 alleviated myocardial injury both in vivo and in vitro. The autophagy level was decreased in type 1 diabetic mice, and Nrg4 intervention reactivated autophagy. Furthermore, Nrg4 intervention was found to activate autophagy via the AMPK/mTOR signalling pathway. Moreover, when autophagy was suppressed or the AMPK/mTOR pathway was inhibited, the beneficial effects of Nrg4 were diminished. CONCLUSION: Nrg4 intervention attenuated diabetic cardiomyopathy by promoting autophagy in type 1 diabetic mice. Additionally, Nrg4 induced autophagy via the AMPK/mTOR signalling pathway.

Bio-Inspired Antibacterial Hydrogel Adhesives with High Adhesion Strength.

Traditional adhesives such as cyanoacrylate glue are mostly solvent-based. They are facing the problem of insufficient adhesion to some substrates, and also from the drawback of volatilization and release of small organic molecules in the process of usage. Therefore, a novel adhesive with non-irritating, high adhesive strength, and antibacterial properties is highly required. In this study, a full physically crosslinked zwitterionic poly(betaine sulfonate methacrylate) (PSBMA) hydrogel is proposed. The physical crosslinking interactions endow the hydrogel with good self-healing properties. Furthermore, the pure physical crosslinking hydrogel can form PSBMA powder adhesive after lyophilization and return to the hydrogel state after hydration. The mechanical properties of PSBMA adhesive can be modulated via adjusting the solid content and initiator dosage. Following the cure process similar to that of snail mucus or insect exoskeletons in nature, the adhesion of the PSBMA adhesive is improved at least 100 times than its wet state. In addition, the PSBMA adhesive is easy to be removed due to the dissociation of cross-linked structures in saltwater environments. Moreover, PSBMA adhesive with antifouling properties can effectively prevent the adhesion of proteins and bacteria, which shows potential applications in the assembly of medical devices.

SIRT1 regulates hypoxia-induced oxidative stress in cardiomyocytes via PI3K/MTOR signaling.

This work was developed to investigate the activation of silent information regulator 1 (SIRT1) to regulate hypoxia-induced oxidative stress in cardiomyocytes through the PI3K/MTOR signaling pathway. For this purpose, 30 SD healthy rats were selected, and 10 of them were randomly selected as the control group. The remaining 20 rats were established as acute myocardial infarction model rats, and randomly divided into model group and activated SIRT1 group. Interventions were performed on rats in each of the 3 groups. ROS staining, inflammatory factors [IL-6, IL-1ß levels], H9c2 cell viability, Caspase3 and Caspase8 activity, antioxidant enzyme indexes [SOD, CAT, MDA levels], SIRT1, PI3K, MTOR, HIF-1α, HO-1, GLUT1 mRNA expression were compared between groups. Results showed that IL-6 and IL-1ß levels were abnormally elevated in the model group compared with the control group (P<0.05). IL-6 and IL-1ß levels decreased in the activated SIRT1 group compared with the model group (P<0. 05). H9c2 cell viability decreased and Caspase3 and Caspase8 activities increased in the model group compared with the control group(P <0.05). H9c2 cell viability increased and Caspase3 and Caspase8 activities decreased in the activated SIRT1 group compared with the model group (P<0.05). SOD and CAT levels were abnormally decreased and MDA levels were abnormally increased in the model group compared with the control group (P<0.05). SOD and CAT levels were abnormally increased and MDA levels were decreased in the activated SIRT1 group compared with the model group (P<0.05). PI3K and SIRT1 expression decreased and MTOR expression increased in the model group compared with the control group (P < 0. 05). PI3K and SIRT1 expression increased and MTOR expression decreased in the activated SIRT1 group compared with the model group(P<0.05). The expression of  HIF-1α, HO-1 and GLUT1 mRNA increased in the model group compared with the control group, and the difference was statistically significant (P <0.05). The expression of HIF-1α, HO-1, and GLUT1 mRNA decreased in the activated SIRT1 group compared with the model group, and the difference was statistically significant (P<0.05). It was concluded that the activation of SIRT1 can regulate PI3K/MTOR signaling pathway, thus reducing hypoxia-induced oxidative stress in cardiomyocytes, inflammatory conditions and enhancing cardiomyocyte viability, with better intervention effects.

FOXO3a-mediated long non-coding RNA LINC00261 resists cardiomyocyte hypoxia/reoxygenation injury via targeting miR23b-3p/NRF2 axis.

Ischemia/reperfusion (I/R)-mediated acute myocardial infarction (AMI) is a major pathological factor implicated in the progression of ischemic heart disease (IHD). Long non-coding RNA plays an important role in regulating the occurrence and development of cardiovascular disease. The aim of this study was to investigate the regulating role of LINC00261 in hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis. The relative expression of LINC00261, miR-23b-3p and NRF2 were determined in rats I/R myocardial tissues and H/R-induced cardiomyocytes. The rat model and cell model of LINC00261 overexpression were established to investigate the biological function of LINC00261 on H9C2 cell. The interaction between LINC00261, miR-23b-3p, NRF2 and FOXO3a was identified using bioinformatics analysis, luciferase reporter assay, RNA immunoprecipitation (RIP) assay, chromatin immunoprecipitation (CHIP) assay and qRT-PCR. The expression of LINC00261 was significantly down-regulated in myocardial tissues and H9C2 cell. Overexpression of LINC00261 improves cardiac function and reduces myocardium apoptosis. Interestingly, transcription factor FOXO3a was found to promote LINC00261 transcription. Moreover, LINC00261 was confirmed as a spong of miR23b-3p and thereby positively regulates NRF2 expression in cardiomyocytes. Our findings reveal a novel role for LINC00261 in regulating H/R cardiomyocyte apoptosis and the potency of the LINC00261/miR-23b-3p/NRF2 axis as a therapeutic target for the treatment of MIRI.

Inhibition of the LncRNA Gpr19 attenuates ischemia-reperfusion injury after acute myocardial infarction by inhibiting apoptosis and oxidative stress via the miR-324-5p/Mtfr1 axis.

Reperfusion therapy after acute myocardial infarction (AMI) can effectively restore the blood supply and nutritional support of ischemic myocardium and save the dying myocardium. However, myocardial ischaemia-reperfusion (I/R) injury has become a new threat to reperfusion therapy for AMI. Many long-chain noncoding RNAs (lncRNAs) are dysregulated by I/R damage. Of these dysregulated lncRNAs, Gpr19 was selected as a potential gene of interest based on its high expression change. We aimed to explore the functional role and molecular mechanism of Gpr19 in I/R injury of AMI. C57BL/6 mice underwent I/R injury as in vivo models. Neonatal rat ventricular cardiomyocytes (NRCMs) exposed to an oxygen glucose deprivation/recovery (OGD/R) system were used as an in vitro model. A TUNEL assay, western blot, and oxidative stress analysis were conducted in this study to determine apoptosis and oxidative stress levels. Our results indicated that inhibition of Gpr19 improves cardiac function and reduces apoptosis and myocardial fibrosis scar formation in vivo. Suppression of Gpr19 attenuates oxidative stress and apoptosis in NRCMs exposed to OGD/R. We further demonstrated that inhibition of Gpr19 decreases oxidative stress and apoptosis in OGD/R-induced NRCMs by regulating miR-324-5p and mitochondrial fission regulator 1 (Mtfr1). We elucidated the functional role and potential molecular mechanism of Gpr19 in I/R injury of AMI, provided a theoretical basis for the importance of Gpr9 in I/R injury, and provided a new perspective for the clinical treatment of I/R injury of AMI.

Exosomal miR-301 derived from mesenchymal stem cells protects myocardial infarction by inhibiting myocardial autophagy.

PURPOSE: To investigate the protective effects of miR-301 in exosomes secreted by bone mesenchymal stem cells (BMSCs) on rats' myocardial infarction (MI). METHODS: After isolation and culture, BMSCs were identified using flow cytometry. Then exosomes were then isolated. Rats MI models were established and they were divided into 4 groups: Sham group, Model group (injected with PBS), BMSC-Exos group (injected with exosomes secreted by BMSCs), BMSC-301-Exos group (injected with exosomes secreted by BMSCs transfected with miR-301 mimics). Cardiac function was assessed by cardiac echocardiography. Myocardial infarct area was measured by Masson trichrome staining mRNA and proteins expression were measured by qRT-PCR and western blot. Exosome morphology and myocardial cells autophagy were observed by transmission electron microscopy. RESULTS: BMSCs were obtained. Rat MI models were successfully established. After rats were injected with exosomes secreted by BMSCs transfected with miR-301 mimics, MI tissues were found to have much higher miR-301 expression, LVEF, LVFS, P62 expression, and remarkably lower LVESD, LVEDD, MI area, LC3-II/LC3-I ratio and autophagosomes numbers compared with BMSC-Exos group (all P < 0.05). CONCLUSION: miR-301 in exosomes secreted by BMSCs protected MI by inhibiting myocardial autophagy.

Integrin ß-3 is required for the attachment, retention and therapeutic benefits of human cardiospheres in myocardial infarction.

Cardiovascular diseases remain the leading causes of death worldwide. Stem cell therapy offers a promising option to regenerate injured myocardium. Among the various types of stem cells, cardiosphere cells represent a mixture of intrinsic heart stem cells and supporting cells. The safety and efficacy of cardiosphere cells have been demonstrated in recent clinical trials. Cell-matrix interaction plays an important role in mediating the engraftment of injected stem cells. Here, we studied the role of integrin ß-3 in cardiosphere-mediated cell therapy in a mouse model of myocardial infarction. Our results indicated that inhibiting integrin ß-3 reduced attachment, retention and therapeutic benefits of human cardiospheres in mice with acute myocardial infarction. This suggests integrin ß-3 plays an important role in cardiosphere-mediated heart regeneration.

The adipocyte clock controls brown adipogenesis through the TGF-ß and BMP signaling pathways.

The molecular clock is intimately linked to metabolic regulation, and brown adipose tissue plays a key role in energy homeostasis. However, whether the cell-intrinsic clock machinery participates in brown adipocyte development is unknown. Here, we show that Bmal1 (also known as ARNTL), the essential clock transcription activator, inhibits brown adipogenesis to adversely affect brown fat formation and thermogenic capacity. Global ablation of Bmal1 in mice increases brown fat mass and cold tolerance, and adipocyte-selective inactivation of Bmal1 recapitulates these effects and demonstrates its cell-autonomous role in brown adipocyte formation. Further loss- and gain-of-function studies in mesenchymal precursors and committed brown progenitors reveal that Bmal1 inhibits brown adipocyte lineage commitment and terminal differentiation. Mechanistically, Bmal1 inhibits brown adipogenesis through direct transcriptional control of key components of the TGF-ß pathway together with reciprocally altered BMP signaling; activation of TGF-ß or blockade of BMP pathways suppresses enhanced differentiation in Bmal1-deficient brown adipocytes. Collectively, our study demonstrates a novel temporal regulatory mechanism in fine-tuning brown adipocyte lineage progression to affect brown fat formation and thermogenic regulation, which could be targeted therapeutically to combat obesity.

Brain and muscle Arnt-like 1 is a key regulator of myogenesis.

The circadian clock network is an evolutionarily conserved mechanism that imparts temporal regulation to diverse biological processes. Brain and muscle Arnt-like 1 (Bmal1), an essential transcriptional activator of the clock, is highly expressed in skeletal muscle. However, whether this key clock component impacts myogenesis, a temporally regulated event that requires the sequential activation of myogenic regulatory factors, is not known. Here we report a novel function of Bmal1 in controlling myogenic differentiation through direct transcriptional activation of components of the canonical Wnt signaling cascade, a major inductive signal for embryonic and postnatal muscle growth. Genetic loss of Bmal1 in mice leads to reduced total muscle mass and Bmal1-deficient primary myoblasts exhibit significantly impaired myogenic differentiation accompanied by markedly blunted expression of key myogenic regulatory factors. Conversely, forced expression of Bmal1 enhances differentiation of C2C12 myoblasts. This cell-autonomous effect of Bmal1 is mediated by Wnt signaling as both expression and activity of Wnt components are markedly attenuated by inhibition of Bmal1, and activation of the Wnt pathway partially rescues the myogenic defect in Bmal1-deficient myoblasts. We further reveal direct association of Bmal1 with promoters of canonical Wnt pathway genes, and as a result of this transcriptional regulation, Wnt signaling components exhibit intrinsic circadian oscillation. Collectively, our study demonstrates that the core clock gene, Bmal1, is a positive regulator of myogenesis, which may represent a temporal regulatory mechanism to fine-tune myocyte differentiation.

Angiotensin II increases secreted frizzled-related protein 5 (sFRP5) expression through AT1 receptor/Rho/ROCK1/JNK signaling in cardiomyocytes.

Secreted frizzled-related protein 5 (sFRP5) is a novel adipokine that functions as an inhibitor of Wnt signaling and is involved in embryonic development, proliferation, atherosclerosis, and apoptosis. Studies have shown that sFRP1-4 is expressed in cardiomyocytes, and sFRP3 and sFRP4 are elevated during heart failure. However, it is unclear whether sFRP5 is expressed in cardiomyocytes or cardiac hypertrophy, and as regards the effects of sFRP5 in the process. Here, we report the expression and the corresponding mechanisms of sFRP5 in angiotensin II (Ang II)-induced cardiomyocyte hypertrophy. Neonatal rat ventricular myocytes were exposed to increasing concentrations of Ang II for 12-72 h. Y27632 was used to block ROCK signal. PD98059, SB203580, and SP600125 were used to inhibit ERK1/2, p38 MAPK, and JNK signaling pathways, respectively, and anisomycin was used to activate JNK pathway. RT-PCR and Western-blot determined the expressions of sFRP5. BNP, TNF-α, ROCK1, ROCK2, MYPT1, and JNK were examined through Western-blot analysis. Ang II increased sFRP5 mRNA and protein levels in a time- and dose-dependent manner. Telmisartan, Y27632 and SP600125 effectively suppressed the expression of sFRP5. sFRP5 downregulated BNP and TNF-α expressions in hypertrophic cardiomyocytes. sFRP5 is expressed in cardiomyocytes, and upregulated in Ang II-induced cardiomyocyte hypertrophy through the AT1 receptor/Rho/ROCK1/JNK signaling pathway. sFRP5 may play an important role during cardiomyocyte hypertrophy.

Chemerin induces insulin resistance in rat cardiomyocytes in part through the ERK1/2 signaling pathway.

AIMS: Chemerin is a novel adipokine that is closely associated with cardiovascular diseases and glucose homeostasis. This study aimed to investigate the effects of chemerin on insulin resistance in rat cardiomyocytes. METHODS: Rat cardiomyocytes were treated with high concentrations of glucose and tumor necrosis factor-alpha (TNF-α), and chemerin and chemokine-like receptor 1 (CMKLR1) were measured by Western blot analysis. Then, the cardiomyocytes were treated with chemerin and insulin. Glucose uptake was evaluated using a fluorescence microplate reader. Western blot analysis was used to evaluate the phosphorylation of Akt, insulin receptor substrate-1, p38 mitogen-activated protein kinase (MAPK), as well as extracellular signal-regulated kinase (ERK)1/2. RESULTS: Chemerin and CMKLR1 were found to be expressed in rat cardiomyocytes. Pretreatment with chemerin caused decreases in glucose uptake and phosphorylation of Akt in insulin-stimulated cardiomyocytes. Furthermore, chemerin activated the phosphorylation of p38 MAPK and ERK1/2 in insulin-stimulated cardiomyocytes. Inhibition of ERK partially rescued chemerin-induced insulin resistance. CONCLUSION: Chemerin is a novel adipokine that induces insulin resistance in rat cardiomyocytes in part through the ERK1/2 pathway.

Bioinformatics analysis and identification of potential key genes and pathways in the pathogenesis of nonischemic cardiomyopathy.

Nonischemic cardiomyopathy (NICM) is a major cause of advanced heart failure, and the morbidity and mortality associated with NICM are serious medical problems. However, the etiology of NICM is complex and the related mechanisms involved in its pathogenesis remain unclear. The microarray datasets GSE1869 and GSE9128 retrieved from the Gene Expression Omnibus database were used to identify differentially expressed genes (DEGs) between NICM and normal samples. The co-expressed genes were identified using Venn diagrams. Kyoto Encyclopedia of Genes and Genomes pathway analyses and gene ontology enrichment were used to clarify biological functions and signaling pathways. Analysis of protein-protein interaction networks using Search Tool for the Retrieval of Interacting Genes/Proteins online to define the hub genes associated with NICM pathogenesis. A total of 297 DEGs were identified from GSE1869, 261 of which were upregulated genes and 36 were downregulated genes. A total of 360 DEGs were identified from GSE9128, 243 of which were upregulated genes and 117 were downregulated genes. In the 2 datasets, the screening identified 36 co-expressed DEGs. Kyoto Encyclopedia of Genes and Genomes pathway and gene ontology analysis showed that DEGs were mainly enriched in pantothenate and CoA biosynthesis, beta-alanine metabolism, kinetochore, G-protein beta/gamma-subunit complex, and other related pathways. The PPI network analysis revealed that DUSP6, EGR1, ZEB2, and XPO1 are the 4 hub genes of interest in the 2 datasets. Bioinformatics analysis of hub genes and key signaling pathways is an effective way to elucidate the mechanisms involved in the development of NICM. The results will facilitate further studies on the pathogenesis and therapeutic targets of NICM.

Enhancing cell cryopreservation with acidic polyamino acids integrated liquid marbles.

Cryopreservation is highly desired for long-term maintenance of the viability of living biosamples, while effective cell cryopreservation still relies heavily on the addition of dimethyl sulfoxide (DMSO) and fetal bovine serum (FBS). However, the intrinsic toxicity of DMSO is still a bottleneck, which could not only cause the clinical side effect but also induce cell genetic variants. In the meantime, the addition of FBS may bring potentially the risk of pathogenic microorganism contamination. The liquid marbles (LMs), a novel biotechnology tool for cell cryopreservation, which not only have a small volume system that facilitated recovery, but the hydrophobic shell also resisted the harm to cells caused by adverse environments. Previous LM-based cell cryopreservation relied heavily on the addition of FBS. In this work, we introduced acidic polyaspartic acid and polyglutamic acid as cryoprotectants to construct LM systems. LMs could burst in an instant to facilitate and achieve ultrarapid recovery process, and the hydrophilic carboxyl groups of the cryoprotectants could form hydrogen bonds with water molecules and further inhibit ice growth/formation to protect cells from cryoinjuries. The L929 cells could be well cryopreserved by acidic polyamino acid-based LMs. This new biotechnology platform is expected to be widely used for cell cryopreservation, which has the potential to propel LMs for the preservation of various functional cells in the future.

A Single-Component Janus Zwitterionic Hydrogel Patch with a Bionic Microstructure for Postoperative Adhesion Prevention.

The development of anti-adhesion hydrogels for preventing postoperative adhesions is an ongoing challenge, particularly in achieving a balance between exceptional antifouling properties and effective in situ tissue retention. In this study, we propose a unique approach with the design of a single-component Janus zwitterionic hydrogel patch featuring a bionic microstructure. The Janus patches were prepared through free radical polymerization of sulfobetaine methacrylate with N, N'-methylenebis(2-propenamide) as the cross-linker. The incorporation of hexagonal facets separated by interconnecting grooves on one side imparts durable and reliable in situ retention capabilities to the Janus hydrogel patch when it is applied to traumatized tissues. The opposing flat surface exhibits outstanding resistance to bacteria, proteins, and cell adhesion, due to the superhydrophilicity and excellent antifouling characteristics of zwitterionic polymers. This dual functionality empowers the Janus hydrogel patch to mitigate adhesions between traumatized and surrounding tissues. The hexagonal and groove bionic microstructures facilitate rapid drainage, promoting swift contact with the tissue for increased adhesion strength, while independent hexagonal microfacets enhance the peeling energy. In an in vivo setting, Janus zwitterionic hydrogel patches with surface microstructures form mutually embedded structures with the cecum surface, minimizing the likelihood of slippage and detachment. Remarkably, in vivo experiments involving abdominal wall cecum injuries illustrate the Janus zwitterionic hydrogel patch's superior anti-adhesion effectiveness compared to commercial controls. Thus, the Janus hydrogel patch, distinguished by its bionic microstructure surface, presents substantial potential in the biomedical field for averting postoperative adhesions.

Chronological-Programmed Black Phosphorus Hydrogel for Responsive Modulation of the Pathological Microenvironment in Myocardial Infarction.

Electroactive hydrogels have garnered extensive interest as a promising approach to myocardial tissue engineering. However, the challenges of spatiotemporal-specific modulation of individual pathological processes and achieving nontoxic bioresorption still remain. Herein, inspired by the entire postinfarct pathological processes, an injectable conductive bioresorbable black phosphorus nanosheets (BPNSs)-loaded hydrogel (BHGD) was developed via reactive oxide species (ROS)-sensitive disulfide-bridge and photomediated cross-linking reaction. Significantly, the chronologically programmed BHGD hydrogel can achieve graded modulation during the inflammatory, proliferative, and maturation phases of myocardial infarction (MI). More details, during early infarction, the BHGD hydrogel can effectively reduce ROS levels in the MI area, inhibit cellular oxidative stress damage, and promote macrophage M2 polarization, creating a favorable environment for damaged myocardium repair. Meanwhile, the ROS-responsive structure can protect BPNSs from degradation and maintain good conductivity under MI microenvironments. Therefore, the BHGD hydrogel possesses tissue-matched modulus and conductivity in the MI area, facilitating cardiomyocyte maturation and electrical signal exchange, compensating for impaired electrical signaling, and promoting vascularization in infarcted areas in the maturation phase. More importantly, all components of the hydrogel degrade into nontoxic substances without adverse effects on vital organs. Overall, the presented BPNS-loaded hydrogel offers an expandable and safe option for clinical treatment of MI.

Injectable Asymmetric Adhesive-Antifouling Bifunctional Hydrogel for Peritoneal Adhesion Prevention.

Peritoneal adhesion is a common problem after abdominal surgery and can lead to various medical problems. In response to the lack of in situ retention and pro-wound healing properties of existing anti-adhesion barriers, this work reports an injectable adhesive-antifouling bifunctional hydrogel (AAB-hydrogel). This AAB-hydrogel can be constructed by "two-step" injection. The tissue adhesive hydrogel based on gallic acid-modified chitosan and aldehyde-modified dextran is prepared as the bottom hydrogel (B-hydrogel) by Schiff base reaction. The aldehyde-modified zwitterionic dextran/carboxymethyl chitosan-based hydrogel is formed on the B-hydrogel surface as the antifouling top hydrogel (T-hydrogel). The AAB-hydrogel exhibits good bilayer binding and asymmetric properties, including tissue adhesive, antifouling, and antimicrobial properties. To evaluate the anti-adhesion effect in vivo, the prepared hydrogels are injected onto the wound surface of a mouse abdominal wall abrasion-cecum defect model. Results suggest that the AAB-hydrogel has antioxidant capacity and can reduce the postoperative inflammatory response by modulating the macrophage phenotype. Moreover, the AAB-hydrogel could effectively inhibit the formation of postoperative adhesions by reducing protein deposition, and resisting fibroblast adhesions and bacteria attacking. Therefore, AAB-hydrogel is a promising candidate for the prevention of postoperative peritoneal adhesions.