Role of Trimethylamine N-Oxide in Heart Failure.

Heart failure (HF) is a clinical syndrome characterizing by typical physical signs and symptomatology resulting from reduced cardiac output and/or intracardiac pressure at rest or under stress due to structural and/or functional abnormalities of the heart. HF is often the final stage of all cardiovascular diseases and a significant risk factor for sudden cardiac arrest, death, and liver or kidney failure. Current pharmacological treatments can only slow the progression and recurrence of HF. With advancing research into the gut microbiome and its metabolites, one such trimethylamine N-oxide (TMAO)-has been implicated in the advancement of HF and is correlated with poor prognosis in patients with HF. However, the precise role of TMAO in HF has not yet been clarified. This review highlights and concludes the available evidence and potential mechanisms associated with HF, with the hope of contributing new insights into the diagnosis and prevention of HF.

Vanadium as a Ti-like mediator boosting electronic transmission in Fe-based MOFs for photocatalytic sterilization.

Efficient metal-organic frameworks (MOFs) photocatalytic bactericidal catalysts are urgently needed in water purification. Herein, a Fe-MOF (MIL-88B-NH2(V1Fe5) with promoted electron transport was achieved by vanadium (V) ions doping and V/Fe ratio optimization, showing excellent photocatalytic bactericidal activity againstE. coliunder visible light irradiation (99.92%). The efficient antibacterial mechanism, V as a Ti-like mediator boosting electronic transmission in MIL-88B-NH2(V1Fe5), was revealed by its band structure, transient photocurrent, electrochemical impedance spectroscopy, and scavenger quenching experiments. The enhancement of photocatalytic bactericidal performance of Fe-MOFs by V-ion-doping was confirmed by two other Fe-MOFs, MIL-53-NH2(V1Fe5) and MIL-101-NH2(V1Fe5), with the same metal ions and ligands, both of which have higher performance than the corresponding undoped MOFs. Among them, MIL-88B-NH2(V1Fe5) exhibits the highest photocatalytic bactericidal activity due to its suitable metal clusters ([M(µ3-O)] cluster) and topological structure (three-dimensional rhomboid network structure). This work demonstrated the amplification effect of V ion doping on electron transport in Fe-MOFs photocatalysts.

Construction of Ferric-Oxide-Doped Nickel-Iron Hydroxide Electrocatalysts by Magnetic-Field-Assisted Chemical Corrosion toward Boosted Oxygen Evolution Reaction.

Transition-metal-based oxygen evolution reaction (OER) catalysts have attracted widespread attention due to their inexpensive prices, unique layered structures, and rich active sites. Currently, designing low-cost, sustainable, and simple synthesis methods is essential for the application of transition-metal-based catalysts. Here, magnetic field (MF)-assisted chemical corrosion, as a novel technology, is adopted to construct superior OER electrocatalysts. The produced Ni(Fe)(OH)2-Fe2O3 electrode exhibits an overpotential of 272 mV at a current density of 100 mA cm-2, presenting a 64 mV reduction compared to the electrode without an MF. The experimental results indicate that an MF can induce the directional growth of Fe2O3 rods and reduce their accumulation. In addition, an external MF is beneficial for the lattice dislocation of the obtained catalysts, which can increase the surface free energy, thus reducing the activation energy and accelerating the electrochemical reaction kinetics. This work effectively combines a magnetic field with chemical corrosion and electrochemical energy, which offers a novel strategy for the large-scale development of environmentally friendly and superior electrocatalysts.

Engineering valence-mismatched Ti4+ into Fe-based metal-organic-frameworks for enhanced photocatalytic CO2 reduction.

A series of low-dose high-valence Ti4+ doped MIL-53-NH2(Fe) photocatalysts were synthesized for visible-light-driven CO2 reduction. The highest CO2-to-CO conversion rate of Ti4+ doped MIL-53-NH2(Fe) was 7.24 mmol g-1 h-1 and the highest CO selectivity was 94% in acetonitrile solvent using [Ru(bpy)3]2+ and triethanolamine.

Sandwich-structured continuous ZIF-8/Ti3C2 MXene/ZIF-8 for efficient sterilization: Enhanced photocatalytic activity, photothermal effect, and environmental safety.

The development of effective water purification systems is crucial for controlling and remediating environmental pollution, especially in terms of sterilization. Herein, we demonstrate elaborately designed composite nanosheets with a sandwich structure, composed of two-dimensional (2D) Ti3C2 MXene nanosheet core and conformal ZIF-8 ultrathin outer layers, and their potential applications in photocatalytic sterilization. The study results indicate that the conformal ZIF-8-MXene nanosheet exhibits an expanded light absorption range (826 nm), improved photothermal conversion efficiency (6.2 °C s-1), and photocurrent response, thus boosting photocatalytic sterilization efficiency (6.63 log10 CFU mL-1) against Escherichia coli under simulated sunlight within 90 min. Interestingly, 2D ZIF-8 layers exhibit positive zeta potential (19 mV), good hydrophilicity (40.6°), and local photogenerated-hole accumulation, possessing efficient bacteria-trapping efficiency. Membrane filters fabricated from optimized composite nanosheets exhibit an outstanding bacteria-trapping and sterilization efficiency (almost 100 %) against Escherichia coli under simulated sunlight within 30 min of the flow photocatalytic experiments. This work not only presents a rational structural design of the conformal and ultrathin anchoring of ZIF-8 onto a 2D conductive material for bacteria-trapping and sterilization, but also opens new opportunities for using metal-organic frameworks in photocatalytic disinfection of drinking water.

Fe-MOF/AuNP-based ratiometric electrochemical immunosensor for the detection of deoxynivalenol in grain products.

A ratiometric assay was designed to improve the sensitivity and reliability of electrochemical immunosensors for deoxynivalenol (DON) detection. The indicator signal caused by the Fe-based metal-organic framework nanocomposites loaded with gold nanoparticles and the internal reference signal from the [Fe(CN)6]3-/4- in the electrolyte came together at the immunosensor. When immunoreactivity occurred, the indicator signals decreased as the concentration of DON increased, while the internal reference signals increased slightly. The ratio of the indicator signal to the internal reference signal was available for reproducible and sensitive monitoring of DON. The prepared immunosensor showed excellent performance in the range from 0.5 to 5000 pg mL-1, and the detection limit was 0.0166 pg mL-1. The immunosensor achieved satisfactory detection toward DON in spiked and actual samples and has a promising application in the control of DON in grain products.

A risk analysis of alpelisib-induced hyperglycemia in patients with advanced solid tumors and breast cancer.

BACKGROUND: Hyperglycemia is an on-target effect of PI3Kα inhibitors. Early identification and intervention of treatment-induced hyperglycemia is important for improving management of patients receiving a PI3Kα inhibitor like alpelisib. Here, we characterize incidence of grade 3/4 alpelisib-related hyperglycemia, along with time to event, management, and outcomes using a machine learning model. METHODS: Data for the risk model were pooled from patients receiving alpelisib ± fulvestrant in the open-label, phase 1 X2101 trial and the randomized, double-blind, phase 3 SOLAR-1 trial. The pooled population (n = 505) included patients with advanced solid tumors (X2101, n = 221) or HR+/HER2- advanced breast cancer (SOLAR-1, n = 284). External validation was performed using BYLieve trial patient data (n = 340). Hyperglycemia incidence and management were analyzed for SOLAR-1. RESULTS: A random forest model identified 5 baseline characteristics most associated with risk of developing grade 3/4 hyperglycemia (fasting plasma glucose, body mass index, HbA1c, monocytes, age). This model was used to derive a score to classify patients as high or low risk for developing grade 3/4 hyperglycemia. Applying the model to patients treated with alpelisib and fulvestrant in SOLAR-1 showed higher incidence of hyperglycemia (all grade and grade 3/4), increased use of antihyperglycemic medications, and more discontinuations due to hyperglycemia (16.7% vs. 2.6% of discontinuations) in the high- versus low-risk group. Among patients in SOLAR-1 (alpelisib + fulvestrant arm) with PIK3CA mutations, median progression-free survival was similar between the high- and low-risk groups (11.0 vs. 10.9 months). For external validation, the model was applied to the BYLieve trial, for which successful classification into high- and low-risk groups with shorter time to grade 3/4 hyperglycemia in the high-risk group was observed. CONCLUSIONS: A risk model using 5 clinically relevant baseline characteristics was able to identify patients at higher or lower probability for developing alpelisib-induced hyperglycemia. Early identification of patients who may be at higher risk for hyperglycemia may improve management (including monitoring and early intervention) and potentially lead to improved outcomes. REGISTRATION: ClinicalTrials.gov: NCT01219699 (registration date: October 13, 2010; retrospectively registered), ClinicalTrials.gov: NCT02437318 (registration date: May 7, 2015); ClinicalTrials.gov: NCT03056755 (registration date: February 17, 2017).

The J bs-5YP peptide can alleviate dementia in senile mice by restoring the transcription of Slc40a1 to secrete the excessive iron from brain.

INTRODUCTION: With age and ATP decrease in the body, the transcription factors hypophosphorylation weakens the transcription of Slc40a1 and hinders the expression of the iron discharger ferroportin. This may lead to iron accumulation in the brain and the catalysis of free radicals that damage cerebral neurons and eventually lead to Alzheimer's disease (AD). OBJECTIVES: To prevent AD caused by brain iron excretion disorders and reveal the mechanism of J bs-5YP peptide restoring ferroportin. METHODS: We prepared J bs-YP peptide and administered it to the senile mice with dementia. Then, the intelligence of the mice was tested using a Morris Water Maze. The ATP content in the body was detected using the ATP hydrophysis and Phosphate precipitation method. The activation of Slc40a1 transcription was assayed with ATAC seq and the ferroportin, as well as the phosphorylation levels of Ets1 in brain were detected by Western Blot. RESULTS: The phosphorylation level of Ets1in brain was enhanced, and subsequently, the transcription of Slc40a1 was activated and ferroportin was increased in the brain, the levels of iron and free radicals were reduced, with the neurons protection, and the dementia was ultimately alleviated in the senile mice. CONCLUSION: J bs-5YP can recover the expression of ferroportin to excrete excessive iron in the brain of senile mice with dementia by enhancing the transcription of Slc40a1 via phosphorylating Ets1, revealing the potential of J bs-5YP as a drug to alleviate senile dementia.

Causal Relationship Between Gut Microbiota and Aneurysm: A Mendelian Randomization Study.

Observational studies have suggested a possible relationship between gut microbiota (GM) and aneurysm development. However, the nature of this association remains unclear due to the inherent limitations of observational research, such as reverse causation and confounding factors. To address this knowledge deficit, this study aimed to investigate and establish a causal link between GM and aneurysm development.

Cardioprotective Strategies After Ischemia-Reperfusion Injury.

Acute myocardial infarction (AMI) is associated with high morbidity and mortality worldwide. Although early reperfusion is the most effective strategy to salvage ischemic myocardium, reperfusion injury can develop with the restoration of blood flow. Therefore, it is important to identify protection mechanisms and strategies for the heart after myocardial infarction. Recent studies have shown that multiple intracellular molecules and signaling pathways are involved in cardioprotection. Meanwhile, device-based cardioprotective modalities such as cardiac left ventricular unloading, hypothermia, coronary sinus intervention, supersaturated oxygen (SSO2), and remote ischemic conditioning (RIC) have become important areas of research. Herein, we review the molecular mechanisms of cardioprotection and cardioprotective modalities after ischemia-reperfusion injury (IRI) to identify potential approaches to reduce mortality and improve prognosis in patients with AMI.

A Functional Electrolyte Containing P-Phenyl Diisothiocyanate (PDITC) Additive Achieves the Interphase Stability of High Nickel Cathode in a Wide Temperature Range.

The lithium-ion batteries (LIBs) with high nickel cathode have high specific energy, but as the nickel content in the cathode active material increases, batteries are suffering from temperature limitations, unstable performance, and transition metal dissolution during long cycling. In this work, a functional electrolyte with P-phenyl diisothiocyanate (PDITC) additive is developed to stabilize the performance of LiNi0.8 Co0.1 Mn0.1 O2 (NCM811)/graphite LIBs over a wide temperature range. Compared to the batteries without the additive, the capacity retention of the batteries with PDITC-containing electrolyte increases from 23 % to 74 % after 1400 cycles at 25 °C, and from 15 % to 85 % after 300 cycles at 45 °C. After being stored at 60 °C, the capacity retention rate and capacity recovery rate of the battery are also improved. In addition, the PDITC-containing battery has a higher discharge capacity at -20 °C, and the capacity retention rate increases from 79 % to 90 % after 500 cycles at 0 °C. Both theoretical calculations and spectroscopic results demonstrate that PDITC is involved in constructing a dense interphase, inhibiting the decomposition of the electrolyte and reducing the interfacial impedance. The application of PDITC provides a new strategy to improve the wide-temperature performance of the NCM811/graphite LIBs.

CircUsp9x/miR-599/stim1 axis regulates proliferation and migration in vascular smooth muscle cells induced by oxidized-low density lipoprotein.

Circular RNAs (circRNAs) regulate the function of vascular smooth muscle cells (VSMCs) in atherosclerosis (AS) progression. We aimed to explore the role of circUSP9X in oxidized low-density lipoprotein (ox-LDL)-induced VSMCs. Cell proliferation was assessed using cell counting kit-8 and EDU assays. Cell migration was evaluated using Transwell and wound healing assays. The interaction between circUSP9X or STIM1 and miR-599 was analyzed using dual-luciferase reporter and RNA pull-down assays. Their levels were examined using quantitative real-time PCR. CircUSP9X and STIM1 expression was increased, whereas miR-599 expression was reduced in the serum of patients with AS and ox-LDL-stimulated VSMCs. Overexpression of circUSP9X facilitated the proliferation and migration of VSMCs induced by ox-LDL. CircUSP9X sponged miR-599, which targeted STIM1. MiR-599 reversed the effects induced by circUSP9X, and STIM1 reversed the effects induced by miR-599. Taken together, CircUSP9X promoted proliferation and migration in ox-LDL-treated VSMCs via the miR-599/STIM1 axis, providing a theoretical basis for the role of circUSP9X/miR-599/STIM1 axis in AS.

Identification of prognostic and diagnostic signatures for cancer and acute myocardial infarction: multi-omics approaches for deciphering heterogeneity to enhance patient management.

Patients diagnosed with cancer face an increased risk of cardiovascular events in the short term, while those experiencing acute myocardial infarction (AMI) have a higher incidence of cancer. Given limitations in clinical resources, identifying shared biomarkers offers a cost-effective approach to risk assessment by minimizing the need for multiple tests and screenings. Hence, it is crucial to identify common biomarkers for both cancer survival and AMI prediction. Our study suggests that monocyte-derived biomarkers, specifically WEE1, PYHIN1, SEC61A2, and HAL, hold potential as predictors for cancer prognosis and AMI. We employed a novel formula to analyze mRNA levels in clinical samples from patients with AMI and cancer, resulting in the development of a new risk score based on expression profiles. By categorizing patients into high-risk and low-risk groups based on the median risk score, we observed significantly poorer overall survival among high-risk patients in cancer cohorts using Kaplan-Meier analysis. Furthermore, calibration curves, decision curve analysis (DCA), and clinical impact curve analyses provided additional evidence supporting the robust diagnostic capacity of the risk score for AMI. Noteworthy is the shared activation of the Notch Signaling pathway, which may shed light on common high-risk factors underlying both AMI and cancer. Additionally, we validated the differential expression of these genes in cell lines and clinical samples, respectively, reinforcing their potential as meaningful biomarkers. In conclusion, our study demonstrates the promise of mRNA levels as biomarkers and emphasizes the significance of further research for validation and refinement.

Low T3 syndrome predicts more adverse events in patients with hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a common cardiac genetic disorder that clinically manifests with sudden death and progressive heart failure. Moreover, thyroid dysfunction is associated with increased cardiovascular morbidity and mortality risks. Therefore, this study aimed to clarify whether thyroid hormones could serve as an independent predictor of adverse events in patients with HCM. METHODS: The cohort consisted of 782 patients with HCM who had thyroid hormones baseline data and were admitted to the Affiliated Hospital of Jiaxing University. Patients were divided into two groups according to serum levels of free triiodothyronine (fT3): the normal fT3 and low triiodothyronine (T3) syndrome groups. Low T3 syndrome was defined as fT3 < 2.43 pmol/L with a normal thyroid-stimulating hormone (TSH) level. Patients whose TSH levels were abnormally high or abnormally low were excluded from this study. The primary endpoint was the occurrence of sudden cardiac death (SCD) events, and the secondary endpoint was a composite of worsening heart failure (WHF) events, including heart failure death, cardiac decompensation, hospitalization for heart failure, and HCM-related stroke. The Kaplan-Meier and Cox regression were performed for the survival analysis. RESULTS: After a median follow-up of 52 months, 75 SCD events and 134 WHF events were recorded. The Kaplan-Meier survival curves showed that the cumulative incidence of SCD events and WHF events were significantly higher in patients with low T3 syndrome (log-rank p = .02 and log-rank p = .001, respectively). Furthermore, multivariate Cox regression analysis demonstrated that low T3 syndrome is a strong predictor of SCD events and WHF events (adjusted hazard ratio [HR: 1.53, 95% confidence interval [CI]: 1.13-2.24, p < .01; HR: 3.87, 95% CI: 2.91-4.98, p < .001, respectively). CONCLUSIONS: Low T3 syndrome is highly prevalent among patients with HCM and was independently associated with an increased risk of SCD events and WHF events. The routine assessment of serum fT3 levels may provide risk stratification in this population.

Organic Molecule Bifunctionalized Polymeric Carbon Nitride for Enhanced Photocatalytic Hydrogen Peroxide Production.

Modifying the polymeric carbon nitride (CN) with organic molecules is a promising strategy to enhance the photocatalytic activity. However, most previously reported works show that interchain embedding and edge grafting of the organic molecule can hardly be achieved simultaneously. Herein, we successfully synthesized organic molecule bifunctionalized CN (MBCN) through copolymerization of melon and sulfanilamide at a purposely elevated temperature of 550 °C. In MBCN, the edge grafted and interchain embedded benzene rings act as the electron-donating group and charge-transfer channel, respectively, rendering efficient photocatalytic H2 O2 production. The optimal MBCN exhibits a significantly improved non-sacrificial photocatalytic H2 O2 generation rate (54.0 µmol g-1 h-1 ) from pure water, which is 10.4 times that of pristine CN. Experimental and density functional theory (DFT) calculation results reveal that the enhanced H2 O2 production activity of MBCN is mainly attributed to the improved photogenerated charge separation/transfer and decreased formation energy barrier (▵G) from O2- to the intermediate 1,4-endoperoxide (⋅OOH). This work suggests that simultaneous formation of electron donating group and charge transfer channel via organic molecule bifunctionalization is a feasible strategy for boosting the photocatalytic activity of CN.

Time-restricted eating with calorie restriction on weight loss and cardiometabolic risk: a systematic review and meta-analysis.

The effect of time-restricted eating (TRE) has been summarized in previous studies, but its benefits in combination with calorie restriction (CR) still need to be determined. The present meta-analysis aimed to evaluate the efficacy of TRE with CR on weight loss and cardiometabolic risk. PubMed, Embase, Cochrane Library, and gray literature databases were searched from inception to October 18, 2022, for potential randomized controlled trial (RCT) studies based on predefined inclusion and exclusion criteria. Body weight and other cardiometabolic risk factors were described as weighted mean difference (WMD) with a 95% confidence interval (CI). Eight RCTs involving 579 participants were enrolled in the present analysis. The pooled results showed that TRE with CR reduced the body weight, fat mass, and waist circumference significantly (WMD: -1.40, 95% CI: -1.81 to -1.00, and I2: 0%; WMD: -0.73, 95% CI: -1.39 to -0.07, and I2: 0%; WMD: -1.87, 95% CI: -3.47 to -0.26, and I2: 67.25%, respectively). However, compared with CR alone, TRE plus CR exhibited no significant benefit on the blood pressure, glucose profile, and lipid profile. Subgroup analysis suggested that early TRE is more effective in weight loss (WMD: -1.42, 95% CI: -1.84 to -1.01, and I2: 0%) and improving fat mass (WMD: -1.06, 95% CI: -1.91 to -0.22, and I2: 0%) than delayed or broader TRE when combined with CR. Although the combination of TRE and CR can effectively decrease body weight, fat mass, and waist circumference, the long-term effects, particularly those on cardiometabolic risk in participants with chronic cardiovascular disease and diabetes, remain to be explored.

Machine learning-based mRNA signature in early acute myocardial infarction patients: the perspective toward immunological, predictive, and personalized.

Patients diagnosed with stable coronary artery disease (CAD) are at continued risk of experiencing acute myocardial infarction (AMI). This study aims to unravel the pivotal biomarkers and dynamic immune cell changes, from an immunological, predictive, and personalized viewpoint, by implementing a machine-learning approach and a composite bioinformatics strategy. Peripheral blood mRNA data from different datasets were analyzed, and CIBERSORT was used for deconvoluting human immune cell subtype expression matrices. Weighted gene co-expression network analysis (WGCNA) in single-cell and bulk transcriptome levels was conducted to explore possible biomarkers for AMI, with a particular emphasis on examining monocytes and their involvement in cell-cell communication. Unsupervised cluster analysis was performed to categorize AMI patients into different subtypes, and machine learning methods were employed to construct a comprehensive diagnostic model to predict the occurrence of early AMI. Finally, RT-qPCR on peripheral blood samples collected from patients validated the clinical utility of the machine learning-based mRNA signature and hub biomarkers. The study identified potential biomarkers for early AMI, including CLEC2D, TCN2, and CCR1, and found that monocytes may play a vital role in AMI samples. Differential analysis revealed that CCR1 and TCN2 exhibited elevated expression levels in early AMI compared to stable CAD. Machine learning methods showed that the glmBoost+Enet [alpha=0.9] model achieved high predictive accuracy in the training set, external validation sets, and clinical samples in our hospital. The study provided comprehensive insights into potential biomarkers and immune cell populations involved in the pathogenesis of early AMI. The identified biomarkers and the constructed comprehensive diagnostic model hold great promise for predicting the occurrence of early AMI and can serve as auxiliary diagnostic or predictive biomarkers.

Selective Photocatalytic Reduction of CO2 to CO Mediated by Silver Single Atoms Anchored on Tubular Carbon Nitride.

Artificial photosynthesis is a promising strategy for converting carbon dioxide (CO2 ) and water (H2 O) into fuels and value-added chemical products. However, photocatalysts usually suffered from low activity and product selectivity due to the sluggish dynamic transfer of photoexcited charge carriers. Herein, we describe anchoring of Ag single atoms on hollow porous polygonal C3 N4 nanotubes (PCN) to form the photocatalyst Ag1 @PCN with Ag-N3 coordination for CO2 photoreduction using H2 O as the reductant. The as-synthesized Ag1 @PCN exhibits a high CO production rate of 0.32 µmol h-1 (mass of catalyst: 2 mg), a high selectivity (>94 %), and an excellent stability in the long term. Experiments and density functional theory (DFT) reveal that the strong metal-support interactions (Ag-N3 ) favor *CO2 adsorption, *COOH generation and desorption, and accelerate dynamic transfer of photoexcited charge carriers between C3 N4 and Ag single atoms, thereby accounting for the enhanced CO2 photoreduction activity with a high CO selectivity. This work provides a deep insight into the important role of strong metal-support interactions in enhancing the photoactivity and CO selectivity of CO2 photoreduction.

[Effects of tropomyosin 3 on pyroptosis of cardiomyocytes and fibroblast activation induced by hypoxia/reoxygenation in rats].

OBJECTIVE: To explore the role of tropomyosin 3 (TPM3) in hypoxia/reoxygenation (H/R)-induced cardiomyocyte pyroptosis and fibroblast activation. METHODS: Rat cardiomyocytes (H9c2 cells) were treated with H/R method to simulate myocardial ischemia/reperfusion (I/R) injury, and cell proliferation activity was evaluated with cell counting kit-8 (CCK8). The expression of TPM3 mRNA and protein was detected by quantitative real-time polymerase chain reaction (RT-qPCR) and Western blotting. H9c2 cells with stable TPM3-short hairpin RNA (shRNA) expression were constructed and treated with H/R (hypoxia for 3 hours, and reoxygenation for 4 hours). The expression of TPM3 was measured by RT-qPCR. The expressions of TPM3, pyroptosis-related proteins including caspase-1, NOD-like receptor protein 3 (NLRP3) and Gasdermin family proteins-N (GSDMD-N) were measured by Western blotting. The expression of caspase-1 was also observed by immunofluorescence assay. The levels of human interleukins (IL-1ß, IL-18) in the supernatant were determined by enzyme-linked immunosorbent assay (ELISA) to elucidate the effect of sh-TPM3 on pyroptosis of cardiomyocytes. Rat myocardial fibroblasts were incubated with the above cell supernatant, and the expressions of human collagen I, collagen III, matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase inhibitor 2 (TIMP2) were detected by Western blotting to determine the effect of TPM3-interfered cardiomyocytes on the activation of fibroblasts under H/R conditions. RESULTS: Compared with the control group, H/R treatment for 4 hours significantly decreased the survival rate of H9c2 cells [(25.81±1.90)% vs. (99.40±5.54)%, P < 0.01], promoted the expression of TPM3 mRNA and protein [TPM3/GAPDH (2-ΔΔCt): 3.87±0.50 vs. 1, TPM3/ß-Tubulin: 0.45±0.05 vs. 0.14±0.01, both P < 0.01], and promoted the expressions of caspase-1, NLRP3, GSDMD-N, and the enhanced release of cytokines IL-1ß and IL-18 [cleaved caspase-1/caspase-1: 0.89±0.04 vs. 0.42±0.03, NLRP3/ß-Tubulin: 0.39±0.03 vs. 0.13±0.02, GSDMD-N/ß-Tubulin: 0.69±0.05 vs. 0.21±0.02, IL-1ß (µg/L): 13.84±1.89 vs. 4.31±0.33, IL-18 (µg/L): 17.56±1.94 vs. 5.36±0.63, all P < 0.01]. However, compared with the H/R group, sh-TPM3 significantly weakened the promoting effects of H/R on these proteins and cytokines [cleaved caspase-1/caspase-1: 0.57±0.05 vs. 0.89±0.04, NLRP3/ß-Tubulin: 0.25±0.04 vs. 0.39±0.03, GSDMD-N/ß-Tubulin: 0.27±0.03 vs. 0.69±0.05, IL-1ß (µg/L): 8.56±1.22 vs. 13.84±1.89, IL-18 (µg/L): 9.34±1.04 vs. 17.56±1.94, all P < 0.01]. In addition, the expressions of collagen I, collagen III, TIMP2, and MMP-2 in myocardial fibroblasts were significantly increased by the cultured supernatants from the H/R group (collagen I/ß-Tubulin: 0.62±0.05 vs. 0.09±0.01, collagen III/ß-tubulin: 0.44±0.03 vs. 0.08±0.00, TIMP2/ß-tubulin: 0.73±0.04 vs. 0.20±0.03, TIMP2/ß-Tubulin: 0.74±0.04 vs. 0.17±0.01, all P < 0.01). However, these boosting effects were weakened by sh-TPM3 (collagen I/ß-Tubulin: 0.18±0.01 vs. 0.62±0.05, collagen III/ß-Tubulin: 0.21±0.03 vs. 0.44±0.03, TIMP2/ß-Tubulin: 0.37±0.03 vs. 0.73±0.04, TIMP2/ß-Tubulin: 0.45±0.03 vs. 0.74±0.04, all P < 0.01). CONCLUSIONS: Interference with TPM3 can alleviate H/R-induced cardiomyocyte pyroptosis and fibroblast activation, suggesting that TPM3 may be a potential target of myocardial I/R injury.