Bone morphogenetic protein 10, a rising star in the field of diabetes and cardiovascular disease.

Early research suggested that bone morphogenetic protein 10 (BMP10) is primarily involved in cardiac development and congenital heart disease processes. BMP10 is a newly identified cardiac-specific protein. In recent years, reports have emphasized the effects of BMP10 on myocardial apoptosis, fibrosis and immune response, as well as its synergistic effects with BMP9 in vascular endothelium and role in endothelial dysfunction. We believe that concentrating on this aspect of the study will enhance our knowledge of the pathogenesis of diabetes and the cardiovascular field. However, there have been no reports of any reviews discussing the role of BMP10 in diabetes and cardiovascular disease. In addition, the exact pathogenesis of diabetic cardiomyopathy is not fully understood, including myocardial energy metabolism disorders, microvascular changes, abnormal apoptosis of cardiomyocytes, collagen structural changes and myocardial fibrosis, all of which cause cardiac function impairment directly or indirectly and interact with one another. This review summarizes the research results of BMP10 in cardiac development, endothelial function and cardiovascular disease in an effort to generate new ideas for future research into diabetic cardiomyopathy.

Canagliflozin combined with aerobic exercise protects against chronic heart failure in rats.

To determine the efficacy and potential protective mechanism of canagliflozin combined with aerobic exercise in treating chronic heart failure (CHF). Isoproterenol was injected into rats to create CHF models. The rats were then subsequently divided into saline, canagliflozin (3 mg/kg/d), aerobic exercise training, and canagliflozin combined with aerobic exercise training. Compared to the CHF group, the canagliflozin combined with the aerobic exercise group had superior ventricular remodeling and cardiac function. In rats treated with canagliflozin combined with aerobic exercise, the expression of cytochrome P450 (CYP) 4A3, CYP4A8, COL1A1, COL3A1, and FN1 was reduced, while the expression of CYP26B1, ALDH1A2, and CYP1A1 increased significantly. Additionally, canagliflozin combined with aerobic exercise decreased the phosphorylation of AKT and ERK1/2. Canagliflozin combined with aerobic exercise has a positive effect on the development of CHF via the regulation of retinol metabolism and the AKT/ERK signaling pathway.

Antimicrobial and anti-biofilm activity of a thiazolidinone derivative against Staphylococcus aureus in vitro and in vivo.

Staphylococcus aureus (S. aureus) causes many infections with significant morbidity and mortality. S. aureus can form biofilms, which can cause biofilm-associated diseases and increase resistance to many conventional antibiotics, resulting in chronic infection. It is critical to develop novel antibiotics against staphylococcal infections, particularly those that can kill cells embedded in biofilms. This study aimed to investigate the bacteriocidal and anti-biofilm activities of thiazolidinone derivative (TD-H2-A) against S. aureus. A total of 40 non-duplicate strains were collected, and the minimum inhibitory concentrations (MICs) of TD-H2-A were determined. The effect of TD-H2-A on established S. aureus mature biofilms was examined using a confocal laser scanning microscope (CLSM). The antibacterial effects of the compound on planktonic bacteria and bacteria in mature biofilms were investigated. Other characteristics, such as cytotoxicity and hemolytic activity, were researched. A mouse skin infection model was used, and a routine hematoxylin and eosin (H&E) staining was used for histological examination. The MIC values of TD-H2-A against the different S. aureus strains were 6.3-25.0 µg/mL. The 5 × MIC TD-H2-A killed almost all planktonic S. aureus USA300. The derivative was found to have strong bacteriocidal activity against cells in mature biofilms meanwhile having low cytotoxicity and hemolytic activity against Vero cells and human erythrocytes. TD-H2-A had a good bacteriocidal effect on S. aureus SA113-infected mice. In conclusion, TD-H2-A demonstrated good bacteriocidal and anti-biofilm activities against S. aureus, paving the way for the development of novel agents to combat biofilm infections and multidrug-resistant staphylococcal infections.IMPORTANCEStaphylococcus aureus, a notorious pathogen, can form a stubborn biofilm and develop drug resistance. It is crucial to develop new anti-infective therapies against biofilm-associated infections. The manuscript describes the new antibiotic to effectively combat multidrug-resistant and biofilm-associated diseases.

Glucose oxidase-like Co-MOF nanozyme-catalyzed self-powered sensor for sensitive detection of trace atrazine in complex environments.

The self-powered sensor (SPS) is a sensor method that does not require the external power source and has the potential for portable detection of environmental contaminants. In this work, for the first time, a biomolecule-free SPS for detection of ultra-trace triazine endocrine disruptor atrazine (ATZ) with high sensitivity and selectivity is constructed using a glucose oxidase (GOD)-like cobalt metal-organic framework (Co-MOF) nanozyme-modified high-performance anode and a molecularly imprinted cathode. By modulating the size and morphology of the prepared materials, Co-MOF nanozyme with superior GOD-like property (Michaelis constant Km = 15.8 mM) has been obtained and modified at the anode to catalyze glucose oxidation with high efficiency and provide energy continuously and stably for the SPS. The separation mode of anodic energy supply-cathodic recognition ensures the recognition effect without affecting the catalytic characteristic of Co-MOF and the output signal of the SPS. The designed SPS has a wide linear range of 1 pM-100 nM and a detection limit as low as 0.65 pM, as well as superior selectivity and good stability. The present work provides a promising approach for the design of self-powered sensors which can be extended to detection of a wider range of environmental pollutants.

Immobilization-Free Photoelectrochemical Aptasensor for Atrazine Based on Bifunctional Graphene Signal Amplification and a Controllable Sulfhydryl-Assembled BiOBr/Ag NP Microinterface.

Immobilization-free sensors (IFSs), with no requirement of fixing the recognition element to the electrode surface, have received increasing attention due to their unique advantages of reusable electrodes, not being limited by the load of the recognition element, and not being easily changed to the structure of the probe. In the present work, an effective visible light-driven immobilization-free photoelectric aptasensor for ultrasensitive detection of atrazine (ATZ) was proposed based on a reusable BiOBr/Ag NP substrate electrode with ultrafast charge transfer. Controllable thiols were used as conditioning agents for the photoelectric signal. The ingeniously designed bifunctional graphene can act as not only a molecular "bridge" for the ATZ aptamer through a strong π-π stacking effect, obtaining a graphene-aptamer complex, serving as a homogeneous recognition element, but also a switch for signal modulation for quantitative detection of target substances. Benefiting from the synergistic effect of the above-mentioned factors, the proposed sensor is capable of ultrasensitive and highly selective detection of ATZ in real water samples with a low detection limit of 1.2 pM and a wide linear range from 5.0 pM to 10.0 nM. Furthermore, it shows high stability, good selectivity, and strong anti-interference ability. Thus, this work has provided a fresh perspective for designing advanced immobilization-free photoelectric sensors and convenient detection of environmental pollutants.

Dual-Photoelectrode Fuel Cell Based Self-Powered Sensor for a Picomole Level Pollutant: Using an In Situ Molecularly Imprinted p-Type Organic Photocathode.

Developing a dual-photoelectrode fuel cell based self-powered sensor (DPFC-SPS) with an ideal signal output capability and high sensitivity performance for the detection of environmental pollutant atrazine (ATZ) has an important value. In this work, the in situ molecularly imprinting functionalized p-type organic semiconductor polyterthiophene (MI-pTTh) is used as a photocathode to construct a DPFC-SPS toward the typical environmental pollutant ATZ for the first time. Due to its excellent photoactivity, higher stability, and superior oxygen reduction reaction activity, pTTh serves as the photocathode material for constructing a self-powered sensing platform with a stable signal output and high photoelectric activity. Based on the sensitive light-triggered large self-bias of the DPFC-SPS, the open circuit potential (EOCV) of the device reaches 1.21 V and the maximum power density (Pmax) reaches 121.5 µW·cm-2, which is much higher than most reported PFC-SPSs. Simultaneously, in situ molecularly imprinted (MI) functionization of pTTh can further endow it with specific recognition ability, helping the constructed SPS achieve high sensitivity, selectivity, and effective recognition of the important environmental pollutants ATZ in complex systems. It exhibits a broad linear relationship from 0.002 to 100 nM and a low detection limit (estimated by S/N > 3) of 0.21 pM toward ATZ. The mechanism of the binding kinetics of the MI-pTTh with the target ATZ is further studied via in situ infrared spectroscopy. This work provides theoretical guidance for sensing strategies using dual-photoelectrode devices and offers a rational device design for cost-effective electricity generation from renewable resources.

Effects of once-weekly glucagon-like peptide-1 receptor agonists on type 2 diabetes mellitus complicated with coronary artery disease: Potential role of the renin-angiotensin system.

AIM: To investigate the potential mechanism of once-weekly glucagon-like peptide-1 receptor agonists (GLP-1 RA) in the treatment of type 2 diabetes mellitus (T2DM) complicated with coronary artery disease (CAD). METHODS: We searched both Chinese and English databases for randomized controlled trials related to once-weekly GLP-1 RA for T2DM complicated with CAD to verify the safety and efficacy of GLP-1 RA. The underlying mechanism was analysed by network pharmacology. RESULTS: In total, 13 studies with 35 563 participants were included in the analysis. The pooled analysis found that dulaglutide, exenatide and semaglutide outperformed placebo in cardiovascular outcomes in patients with T2DM, with a significant reduction in the incidence of non-fatal stroke (p < .00). Levels of cardiovascular risk factors were significantly reduced in the once-weekly GLP-1 RA group compared with the conventional treatment group (glycated haemoglobin: p < .00; fasting blood glucose: p < .00; weight: p < .00; systolic blood pressure: p < .00; total cholesterol: p < .00; low-density lipoprotein cholesterol: p < .00). Network pharmacology results were enriched to the renin-angiotensin system, and matrix metalloproteinase 2 and renin (REN) may be the key targets. In addition, four key targets of dulaglutide, five key targets of exenatide and two key targets of semaglutide were enriched. CONCLUSIONS: Our study suggests that once-weekly GLP-1 RA may have a potential protective effect on cardiovascular events in patients with T2DM combined with CAD, possibly through the renin-angiotensin system. However, further research is needed to confirm these findings and determine cause and effect.

A highly sensitive and selective photoelectrochemical aptasensor for atrazine based on Au NPs/3DOM TiO2 photonic crystal electrode.

A photoelectrochemical (PEC) sensing platform with high sensitivity and selectivity has been fabricated based on Au nanoparticles (Au NPs) modified three dimensionally ordered macroporous (3DOM) TiO2 nanostructure frame for trace detection of an endocrine disrupting pesticide, atrazine (ATZ). The resultant photoanode (Au NPs/3DOM TiO2) shows enhanced PEC performance under visible light due to multi signal amplification of the unique structure of 3DOM TiO2 and surface plasmon resonance (SPR) of Au NPs. ATZ aptamers are used as recognition elements and immobilized on Au NPs/3DOM TiO2 by Au-S bond in large packing density and dominant spatial orientation. The specific recognition and high binding affinity between aptamer and ATZ provides the PEC aptasensor with excellent sensitivity. The detection limit is 0.167 ng/L. Besides, this PEC aptasensor exhibits outstanding anti-interference ability in 100-fold concentration of other endocrine disrupting compounds and has been applied successfully to analyze ATZ in real water samples. A simple but efficient PEC aptasensing platform has therefore been successfully developed with high sensitivity, selectivity and repeatability for pollutant monitoring and potential risk evaluation in the environment with great application prospect.

Molecular characterization and virulence gene profiling of methicillin-resistant Staphylococcus aureus associated with bloodstream infections in southern China.

Methicillin-resistant Staphylococcus aureus (MRSA) causes an enormous illness burden, including skin and soft tissue infections (SSTIs), pneumonia, bloodstream infections (BSI), and sepsis. BSI are associated with significant patient morbidity and mortality worldwide. However, limited information is available on MRSA-related BSI in China. This study aimed to investigate the molecular characterization of 77 MRSA isolates recovered from hospitalized patients with BSI between 2012 and 2020 at three first-class tertiary hospitals in southern China based on multilocus sequence typing (MLST), spa typing, and staphylococcal cassette chromosome mec (SCCmec) typing. Overall, 13 clonal complexes (CCs) were identified, with CC59 and CC5 being the largest clusters, indicating high genetic diversity among BSI-causing MRSA isolates. ST59 was the most prevalent MLST type (22.1%). ST5/ST764-MRSA SCCmec II was the predominant adult MRSA clone, whereas ST59-MRSA SCCmec IV was the most common pediatric MRSA clone. ST5-t2460, ST764-t1084, and ST59-t437 were the most common types of adult MRSA isolates, whereas ST59-t437 and ST59-t172 were the predominant types of children's MRSA isolates. ST59-SCCmec IV/V represented the most common clone among community acquired-MRSA isolates. ST5/ST764-SCCmec II was the most common type of hospital-associated MRSA isolate. The most prevalent toxin-encoding genes detected were hla, hld, icaA, and clfA (96.1-100%). Forty-three (100%, 43/43) isolates harbored more than 18 of the tested virulence genes in adults and eight virulence genes (23.5%, 8/34) in children. Virulence gene analysis revealed diversity among different clones: the positivity rates for the Panton-Valentine leukocidin (PVL) gene were 55.8 and 35.3% in adult and pediatric MRSA isolates, respectively; the genes seb-sei were present in all adult strains; seb-seg-sei-seo were present in all ST5, ST59, ST15, ST45, and ST22 adult strains; and seg-sei-sem-sen-seo were present in different clones, including ST15, ST45, and ST22 adult MRSA isolates and ST25, ST30, ST546, and ST72 children's MRSA isolates. Adult MRSA isolates had significantly higher antibiotic resistance rates and virulence gene prevalence than pediatric MRSA isolates. For 8 years, this study provided epidemiological data on the molecular characteristics and virulence genes in different groups of MRSA BSI in China. Our findings may provide critical information for a better understanding of MRSA BSI.

Exploration of the main active components and pharmacological mechanism of Yerba Mate based on network pharmacology.

INTRODUCTION: Yerba mate is widely consumed in South American countries and is gaining popularity around the world. Long-term consumption of yerba mate has been proven to have health-care functions and therapeutic effects on many diseases; however, its underlying mechanism has not been clearly elucidated. In this research, we explored the pharmacological mechanism of yerba mate through a network pharmacological approach. MATERIAL AND METHODS: The bioactive components of yerba mate were screened from published literature and the Traditional Chinese Medicine System Pharmacology Database (TCMSP), and the targets and related diseases were retrieved by TCMSP. Furthermore, the component-target-disease network an protein-protein interaction (PPI) network were constructed, and combined with gene ontology (GO) functional analysis and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis to explore the pharmacological mechanism of yerba mate. RESULTS: As a result, 16 bioactive components of yerba mate were identified, which acted on 229 targets in total. Yerba mate can be used to treat 305 diseases, such as breast cancer, asthma, Alzheimer's disease, osteoarthritis, diabetes mellitus, atherosclerosis, and obesity. Protein kinase B (AKT1), signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase 1 (MAPK1), transcription factor AP-1 (JUN), cellular tumour antigen (p53) TP53, tumour necrosis factor (TNF), transcription factor p65 (RELA), interleukin-6 (IL6), amyloid-beta precursor protein (APP), and vascular endothelial growth factor A (VEGFA) were identified as the key targets of yerba mate playing pharmacological roles. The signalling pathways identified by KEGG pathway enrichment analysis that were most closely related to the effects of yerba mate included pathways in cancer, fluid shear stress and atherosclerosis, and human cytomegalovirus infection. CONCLUSION: the results of our study preliminarily verify the basic pharmacological action and possible mechanism of yerba mate and provide a reference for the further development of its medicinal value.

Self-powered aptasensor for picomole level pollutants based on a novel enzyme-free photofuel cell.

Atrazine (ATZ) is a highly toxic chlorine-containing aromatic structural triazine endocrine disruptor. Due to its chemical stability and electrochemical inertness, it is of great challenge and significance to establish a simple, portable, and in situ electrochemical sensor for ATZ. In the present work, a self-powered aptasensor (SPA) based on a novel enzyme-free photofuel cell (PFC) is successfully developed for ATZ for the first time. The designed SPA is constructed by the Ti-Fe-O nanotubes/nickel hydroxide (Ti-Fe-O NTs/Ni(OH)2) photoanode and Au/aptamer (Au/Apt) cathode, responsible for the spontaneous generation of electrons and specific recognition of ATZ, respectively. It is worth noting that Ti-Fe-O NTs on the photoanode can exhibit good visible-light absorption property, and modified Ni(OH)2 further enhances the photo-generated carrier separation and improves the output power generation of the SPA. The recognition is set at the cathode to ensure the detection of ATZ and the anti-interference ability. Under the separation mode, the constructed SPA has a high output power (390 µW cm-2), much better than most previous reports. It can further show specific recognition of ATZ with prominent sensitivity and a limit of detection (LOD) as low as 5.4 pM. Moreover, it has been applied to the real water sample analysis with satisfactory results. A promising self-powered sensing platform based on an enzyme-free PFC has therefore been provided for picomole level pollutants with high sensitivity and outstanding selectivity.

Calcium dobesilate efficiency in the treatment of diabetic kidney disease through suppressing MAPK and chemokine signaling pathways based on clinical evaluation and network pharmacology.

Aims: To evaluate the effectiveness and potential mechanism of calcium dobesilate (CaD) in diabetic kidney disease (DKD) patients. Methods: We searched for available randomized controlled studies on DKD patients' treatment with CaD through open databases. Continuous variables were expressed as standardized mean difference (SMD) with a 95% confidence interval (CI). The putative targets and possible pathways of CaD on DKD were analyzed by network pharmacology. Molecular docking was employed to verify the match between CaD and the target genes. Results: In the meta-analysis, 42 trials were included, involving 3,671 DKD patients, of which 1,839 received CaD treatment in addition to conventional treatment, while 1,832 received conventional treatment. Compared with routine therapy, the levels of serum creatinine (Scr) and blood urea nitrogen (BUN) significantly decreased in the CaD treatment (early stage of DKD, Scr: p < 0.00001; BUN: p < 0.0001; clinical stage of DKD, Scr: p < 0.00001; BUN: p < 0.00001; kidney failure stage, Scr: p = 0.001; BUN: p = 0.004). The levels of serum cystatin C (Cys-C), urine levels of molecules reflecting kidney function (urinary albumin excretion rate (UAER) and micro glycoprotein), and inflammatory factors [hypersensitive c-reactive protein (hs-CRP)] were reduced compared with control groups, while glomerular filtration rate (GFR) was increased in patients treated with CaD for 12 weeks. CaD also showed a better effect on improving endothelial function. Network pharmacology results showed that the interaction pathway between CaD and DKD was mainly enriched in MAPK and chemokine signaling pathways. AKT1, CASP3, IGF1, MAPK8, and CCL5 might be the key targets for CaD in treating DKD. Conclusion: Combination with CaD is effective and safe in patients with DKD. Inhibition of MAPK and chemokine signaling pathways might be vital in treating CaD in DKD patients.

Effect of dapagliflozin on diabetic patients with cardiovascular disease via MAPK signalling pathway.

Clinical studies have shown that dapagliflozin can reduce cardiovascular outcome in patients with type 2 diabetes mellitus (T2DM), but the exact mechanism is unclear. In this study, we used the molecular docking and network pharmacology methods to explore the potential mechanism of dapagliflozin on T2DM complicated with cardiovascular diseases (CVD). Dapagliflozin's potential targets were predicted via the Swiss Target Prediction platform. The pathogenic targets of T2DM and CVD were screened by the Online Mendelian Inheritance in Man (OMIM) and Gene Cards databases. The common targets of dapagliflozin, T2DM and CVD were used to establish a protein-protein interaction (PPI) network; the potential protein functional modules in the PPI network were found out by MCODE. Metascape tool was used for Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analysis. A potential protein functional module with the best score was obtained from the PPI network and 9 targets in the protein functional module all showed good binding properties when docking with dapagliflozin. The results of KEGG pathway enrichment analysis showed that the underlying mechanism mainly involved AGE-RAGE signalling pathway in diabetic complications, TNF signalling pathway and MAPK signalling pathway. Significantly, the MAPK signalling pathway was considered as the key pathway. In conclusion, we speculated that dapagliflozin played a therapeutic role in T2DM complicated with CVD mainly through MAPK signalling pathway. This study preliminarily reveals the possible mechanism of dapagliflozin in the treatment of T2DM complicated with CVD and provides a theoretical basis for future clinical research.