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Aim: Pulmonary hypertension due to left heart disease (PH-LHD) is commonly seen in patients with heart failure (HF), but there are limited treatment options. Recent studies have shown an association between aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphisms and pulmonary hypertension (PH). Therefore, this study aimed to investigate the occurrence of ALDH2 rs671 polymorphisms, and the association between ALDH2 and risk of PH-LHD in patients with HF. It also investigated different ALDH2 genotypes and examined their association with cardiac structure and function in HF patients with PH-LHD., Methods: A total of 178 HF patients were consecutively enrolled in this study: 102 without PH-LHD and 76 with PH-LHD. Clinical data, parameters of echocardiography, and relevant biochemical indexes were recorded in both groups. Differences in data obtained between groups were compared, and the risk of variant ALDH2 polymorphisms with PH-LHD in HF patients was analysed using univariate and multivariate logistic regression., Results: The prevalence of ALDH2 rs671 GA/AA polymorphisms (variant ALDH2) was 24 of 102 patients (23.53%) in the HF without PH-LHD group, and 32 of 76 patients (42.10%) in the HF with PH-LHD group, with a statistically significant difference. Univariate and multivariate logistical regression showed that variant ALDH2 is an independent risk factor for HF combined with PH-LHD. A higher proportion of patients with variant ALDH2 in the HF with PH-LHD group had a tricuspid regurgitation velocity >2.8 m/s, and they had higher values of peak early diastolic velocity of the mitral orifice/peak velocity of the early diastolic wave of the mitral orifice, maximum frequency shift of pulmonary valve flow, and pulmonary artery stiffness., Conclusions: Variant ALDH2 may be an independent risk factor for HF combined with PH-LHD. Variant ALDH2 may also be involved in pulmonary artery remodelling and is a potential new target for clinical treatment of PH-LHD., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Existing research has shown that retinol binding protein (RBP4) has an impairing effect on arterial elasticity and induces insulin resistance, but the clinical value of RBP4 in patients with coronary heart disease (CHD) combined with type 2 diabetes mellitus (T2DM) has not been investigated. This study sought to compare the complexity of coronary artery lesions and coronary artery elasticity between patients with CHD combined with T2DM and those with CHD without T2DM, analyze the risk factors affecting coronary artery elasticity, and investigate the value of RBP4 in assessing coronary artery elasticity in patients with CHD and T2DM., Methods: A total of 130 patients with confirmed CHD were consecutively enrolled, including 38 patients with CHD combined with T2DM and 92 patients with CHD without T2DM. Basic clinical data, laboratory findings, coronary angiography and intravascular ultrasound (IVUS) imaging data, and Gensini scores and coronary artery elasticity parameters were calculated in both groups. Elasticity parameters included: stiffness parameter ( β ), pressure-strain elastic modulus ( E p ), distensibility coefficient (DC), and compliance coefficient (CC). Multiple linear regression equations were established with elasticity parameters as dependent variables to explore the factors influencing coronary artery elasticity parameters in patients within the two groups., Results: Compared with patients in the CHD without T2DM group, patients in the CHD combined with T2DM group had higher RBP4 levels, Gensini scores, β and E p values, and lower DC and CC values. Linear regression analysis showed that Gensini score increased with higher β and E p values and decreased with higher DC and CC values. In all patients in the CHD and CHD combined with T2DM groups, RBP4 was an independent risk factor for β values after correction for confounders by multiple linear regression analysis, whereas in patients in the CHD without T2DM group, the effect of RBP4 on β values was not statistically different., Conclusions: RBP4 was an independent risk factor of coronary artery elasticity in CHD patients with T2DM and in overall CHD patients, but it did not affect coronary artery elasticity in CHD patients without T2DM., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 The Author(s). Published by IMR Press.)

Superbacteria-induced skin wound infections are huge health challenges, resulting in significant financial and medical costs due to notable morbidity and mortality worldwide. Probiotics are found in the skin and are effective in treating bacterial infection, moderating the microbial dysbiosis and inflammation induced by pathogens, regulating the immune system, as well as even promoting tissue repair. However, improving their colonization efficiency and viability remains a large obstacle for proper applications. Inspired by probiotic therapy and the natural extracellular matrix structure, hyaluronate-adipic dihydrazide/aldehyde-terminated Pluronic F127/fucoidan hydrogels loaded with Lactobacillus rhamnosus (HPF@L.rha) with unique (bio)physicochemical characteristics were developed through the dynamic Schiff-base reaction for superbacteria-infected trauma management. The developed HPF@L.rha exhibit a shortened gelation time, enhanced mechanical strength, and excellent self-healing and liquid-absorption abilities. Importantly, their anti-superbacteria ( Pseudomonas aeruginosa ) effect was greatly increased in a dose-dependent fashion. Additionally, in vitro evaluation shows that the prepared HPF@L.rha containing appropriate probiotic concentrations (less than 1 × 10 7 CFU/mL) possess satisfactory cytocompatibility and blood compatibility. Further, compared to the HPF hydrogel, in vivo the hydrogel combined with probiotics significantly inhibits P. aeruginosa infection and inflammation, promotes the formation of re-epithelialization and collagen, and thus accelerates full-thickness superbacteria-infected wound repair, which is comparable to commercial Prontosan gel formulation. This work suggests that the combination of biomimicking hydrogels and probiotic therapy displays the great potential to manage superbug-infected trauma.

Soft-tissue trauma emergency caused by natural disasters and traffic accidents is highly prevalent, which can result in massive bleeding, pathogen infection, and even death. Although numerous tissue adhesives can bind to tissue surfaces and cover wounds, most of them still have several deficiencies, including long gelation time, poor adhesive strength, and anti-infection, making them inappropriate for use as first-aid bandages. Herein, injectable and self-healing four-arm-PEG-CHO/polyethyleneimine (PEI) tissue adhesives as liquid first-aid supplies are developed via the dynamic Schiff base reaction for trauma emergency. It is found that the prepared hydrogel adhesives exhibit short and controlled gelation time (9∼88 s), strong adhesive strength, and excellent antibacterial ability. Their hemostatic and antimicrobial performances can be tailored by the mass ratio of four-arm-PEG-CHO/PEI. Moreover, in vitro biological assays display that the developed tissue adhesives possess satisfactory cyto/hemocompatibility. Importantly, in vivo the designed adhesives show fast hemostatic capacity and excellent anti-infection as compared to commercial Prontosan gel. Thus, this work indicates that the four-arm-PEG-CHO/PEI first-aid tissue adhesives display great potential for wound emergency management.

Background: Retinol binding protein 4 (RBP4), a biomarker for insulin resistance in type 2 diabetes (DM), is increased in heart failure. This case-control study aims to determine the association between serum RBP4 levels and diabetic cardiomyopathy (DCM)., Methods: Demographic and clinical data were obtained from 245 DM patients and 102 non-diabetic controls. RBP4 levels were measured using ELISA. The association between RBP4 and DCM was evaluated using multivariate logistic regression and restricted cubic splines (RCS) in DM patients., Results: We showed that serum RBP4 levels were higher in DCM patients than in DM patients without DCM or the controls. Multivariate analysis adjusted by age, gender, body mass index, diabetes duration, left ventricular ejection fraction, insulin treatment, triglycerides, low-density lipoprotein cholesterol, estimated glomerular filtration rate, diabetic retinopathy, diabetic nephropathy, diabetic neuropathy and log N-terminal proBNP showed a significant association between RBP4 and DCM (highest vs. lowest tertile OR 16.87, 95% CI: 6.58, 43.23, p < 0.001). RCS displayed a positive linear correlation between RBP4 levels and the risk of DCM in diabetes ( p = 0.004). Adding RBP4 to a basic risk model for DCM improved the reclassification (Net reclassification index: 87.86%, 95% CI: 64.4%, 111.32%, p < 0.001)., Conclusions: The positive association between serum RBP4 and DCM suggested the role of RBP4 as a potential diagnostic biomarker for distinguishing DCM in patients with DM., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2022 The Author(s). Published by IMR Press.)

The morbidity and mortality of cardiovascular diseases (CVDs) have been increasing year by year all over the world and expanding greatly to the younger population, which becomes the leading causes of death globally that threatens human life safety. Prediction of the occurrence of diseases by using risk related adverse events is crucial for screening and early detection of CVDs. Thus, the discovery of new biomarkers that related to risks of CVDs are of urgent in the field. Retinol-binding protein 4 (RBP4) is a 21-kDa adipokine, mainly secreted by adipocytes. Besides its well-established function in the induction of insulin resistance, it has also been found in recent years to be closely associated with CVDs and other risk factors, such as hypertension, coronary heart disease, heart failure, obesity, and hyperlipidemia. In this review, we mainly focus on the progress of research that establishes the correlation between RBP4 and CVDs and the corresponding major risk factors in recent years., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Ji, Song, Su and Gu.)

Fucoidan has received much attention in healthy food and biomedicine owing to their unique (bio)physicochemical properties, particularly antibacterial and antiviral. Pathogenic microorganisms and probiotics are coexisting in many tissues (e.g., gut, oral, and vagina). However, the effect of fucoidan on probiotics has not been examined. Herein, fucoidan sterilized by different methods (i.e., 0.22 μm filter and high-temperature autoclave) is applied to explore its effect on the responses of Lactobacillus rhamnosus. It is found that high-temperature autoclave treatment causes the depolymerization of fucoidan. Further, the proliferation, morphology, and metabolism of probiotics are greatly dependent on the concentrations of fucoidan. The formation of probiotic biofilm is reduced with an increased concentration of fucoidan. Moreover, the antibacterial ability of probiotics initially increases and then decreases with an increased concentration of fucoidan. Thus, fucoidan could serve as a new marine-origin prebiotic, offering new insight into probiotic modulation and its application in inhibiting bacterial infections., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Bacterial/fungal biofilm-mediated persistent endodontic infections (PEIs) are one of the most frequent clinical lesions in the oral cavity, resulting in apical periodontitis and tooth damage caused by loss of minerals. The conventional root canal disinfectants are poorly bio-safe and harmful to teeth and tissues, making them ineffective in treating PEIs. The development of nanomaterials is emerging as a promising strategy to eradicate disease-related bacteria/fungi. Herein, glucose oxidase (GOx)-modified magnetic nanoparticles (MNPs) were synthesized via a facile and versatile route for investigating their effects on removing PEI-related bacterial/fungal biofilms. It is found that GOx was successfully immobilized on the MNPs by detecting the changes in the diameter, chemical functional group, charge, and magnetic response. Further, we demonstrate that GOx-modified MNPs (GMNPs) exhibit highly effective antibacterial activity against Enterococcus faecalis and Candida albicans . Moreover, the antibacterial/fungal activity of GMNPs is greatly dependent on their concentrations. Importantly, when placed in contact with bacterial/fungal biofilms, the dense biofilm matrix is destructed due to the movement of GMNPs induced by the magnetic field, the formation of reactive oxygen species, and nutrient starvation induced by GOx. Also, the in vitro experiment shows that the as-prepared GMNPs have excellent cytocompatibility and blood compatibility. Thus, GMNPs offer a novel strategy to treat bacteria/fungi-associated PEIs for potential clinical applications.

Conventional wound-dressing materials with structural and functional deficiencies are not effective in promoting wound healing. The development of multifunctional wound dressings is emerging as a promising strategy to accelerate blood coagulation, inhibit bacterial infection, and trigger full-thickness wound into a regenerative process. Herein, multifunctional composite sponges were developed by incorporation of traditional Chinese medicine Kangfuxin (KFX) into alginate (AG)/carboxymethyl chitosan (CMC) via green crosslinking, electrostatic interaction, and freeze-drying methods. It is demonstrated that the AG/CMC/KFX (ACK) sponges exhibit a highly interconnected and porous structure, suitable water vapor transmittance, excellent elastic properties, antibacterial behavior, cytocompatibility, and rapid hemostasis. Further, in a rat full-thickness wounds model, the ACK sponge containing 10% KFX (ACK-10) significantly facilitates wound closure compared to the AC group and ACK sponge containing 5% and 15% KFX. Thus, the multifunctional ACK-10 composite sponge has great promise for the application of full-thickness wound healing., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2020. Published by Elsevier B.V.)

Chitosan and its derivatives have been increasingly used for bacteriostasis. To date, the effect of chitosan and N -(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (HTCC) on Enterococcus faecalis ( E. faecalis ) associated with endodontic infection has remained to be determined. Chitosan and HTCC were serially diluted with double-distilled water (DDW) or PBS at concentrations of 20-2,500 µ g/ml. Various strains of E. faecalis (American Type Tissue Collection no. 29212, as well as isolated strains P25RC and P52Sa) in plankton were adjusted to an optical density at 600 nm of 0.10 and treated with chitosan or HTCC. A colony-forming unit assay was used to determine the concentration of residual bacteria after treatment. Furthermore, E. faecalis biofilms were cultured on coverslips and treated with chitosan or HTCC. The coverslips were rinsed, stained using Live/dead ® BacLight™ bacterial viability kit and observed under an inverted fluorescence microscope. In addition, biofilms on dentine blocks were prepared and observed under a scanning electron microscope. MC3T3-E1 pre-osteoblasts were seeded on 96-well plates and treated with chitosan or HTCC at various concentrations. The cytotoxicity of chitosan and HTCC on MC3T3-E1 pre-osteoblasts was detected using a Cell Counting Kit-8 assay after 24, 48 and 72 h of treatment. The results revealed that the final minimum bactericidal concentrations (MBC) of chitosan and HTCC dissolved in DDW were 70 and 140 µ g/ml, respectively. Chitosan and HTCC in DDW exerted a significantly greater antibacterial effect as compared with that in PBS (P<0.05). At the MBC, chitosan and HTCC in DDW, but particularly chitosan, had a significant antibacterial effect on E. faecalis biofilm. Chitosan exhibited no cytotoxicity to MC3T3-E1 pre-osteoblasts at a concentration of <625 µ g/ml, while HTCC inhibited the proliferation of the cells in the concentration range of 39-10,000 µ g/ml. In conclusion, chitosan and HTCC exhibited prominent antibacterial properties on E. faecalis in the planktonic state and as a biofilm via charge interaction, indicating their potential for application in root canal disinfection and fillings., (Copyright: © Wang et al.)