Relevant, predictive normal, or disease model systems are of vital importance for drug development. The difference between nonhuman models and humans could contribute to clinical trial failures despite ideal nonhuman results. As a potential substitute for animal models, human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes (CMs) provide a powerful tool for drug toxicity screening, modeling cardiovascular diseases, and drug discovery. Here, we review recent hiPSC-CM disease models and discuss the features of hiPSC-CMs, including subtype and maturation and the tissue engineering technologies for drug assessment. Updates from the international multisite collaborators/administrations for development of novel drug discovery paradigms are also summarized.

Diabetic foot ulceration is a common chronic diabetic complication. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been widely used in regenerative medicine owing to their multipotency and easy availability. We developed poly(lactic-co-glycolic acid) (PLGA)-based scaffold to create hUC-MSC tissue sheets. In vitro immunostaining showed that hUC-MSC tissue sheets formed thick and solid tissue sheets with an abundance of extracellular matrix (ECM). Diabetic wounds in mice treated with or without either the hUC-MSC tissue sheet, hUC-MSC injection, or fiber only revealed that hUC-MSC tissue sheet transplantation promoted diabetic wound healing with improved re-epithelialization, collagen deposition, blood vessel formation and maturation, and alleviated inflammation compared to that observed in other groups. Taken collectively, our findings suggest that hUC-MSCs cultured on PLGA scaffolds improve diabetic wound healing, collagen deposition, and angiogenesis, and provide a novel and effective method for cell transplantation, and a promising alternative for diabetic skin wound treatment.

In clinical practice, psoriasis is a prevalent chronic inflammatory cutaneous disease featured with the development of red plaque with silvery scales, which considerably affects cutaneous health and quality of life of those afflicted. This research aimed to examine the association between the body roundness index (BRI) and psoriasis, using data sourced from the National Health and Nutrition Examination Survey (NHANES). Our study used a cross-sectional design, including 8,479 adults, of whom 234 were diagnosed with psoriasis. Multivariable logistic regression was used to analyze the relationship between BRI and psoriasis, with stepwise adjustments for covariables. Results from multivariable logistic regression analyses indicated a significant positive relationship between BRI and the risk of developing psoriasis; specifically, after comprehensive adjustment for covariables, per 1 unit increase in BRI was linked to an 11% rise in psoriasis risk (OR = 1.11, 95% CI = 1.05–1.17). Furthermore, psoriasis patients exhibited higher average BRI compared to non-psoriasis patients and a greater prevalence of comorbidities such as hypertension and smoking. These findings suggest that higher BRI is positively correlated with the risk of psoriasis in the adult population in the US. BRI could potentially act as a practical anthropometric index for more accurately predicting the risk of developing psoriasis.

The triglyceride-glucose (TyG) index, a measure of insulin resistance, has been confirmed to be associated with adverse clinical outcomes. A new composite

Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been widely used in therapy of ischemic heart disease. However, there are still remaining issues that limit the therapeutic efficacy, such as immune rejection and low retention of hiPSC-CMs. Human adipose mesenchymal stromal cells (hADSCs) have been reported to be able to regulate the immune response, promote angiogenesis and promote the maturation of hiPSC-CMs. In this study, we co-cultured these two types of cells on fiber scaffold made of biodegradable poly (D,L-lactic-co-glycolic acid) (PLGA) polymer for several days to develop a composited 3D cardiac tissue sheet. As expected, the cells formed 231.00 ± 15.14 μm thickness tissue, with improved organization, alignment, ECM condition, contractile ability, and paracrine function compared to culture hiPSC-CMs only on PLGA fiber. Furthermore, the composited 3D cardiac tissue sheet significantly promoted the engraftment and survival after transplantation. The composited 3D cardiac tissue sheet also increased cardiac function, attenuated ventricular remodeling, decreased fibrosis, and enhanced angiogenesis in rat myocardial infarction model, indicating that this strategy wound be a promising therapeutic option in the clinical scenario.

Chronic respiratory diseases (CRD) represents a series of lung disorders and is posing a global health burden. Systemic inflammation and phenotypic ageing have been respectively reported to associate with certain CRD. However, little is known about the co-exposures and mutual associations of inflammation and ageing with CRD. Here, we aim to systematically elucidate the joint and mutual mediating associations of systemic immune-inflammation index (SII) and phenotypic age acceleration (PhenoAgeAccel) with CRD based on data from National Health and Nutrition Examination Survey (NHANES). Data for this study was obtained from NHANES 2007–2010 and 2015–2018. The single and combined associations of SII and PhenoAgeAccel with CRD were analyzed using multivariable logistic regression models. The dose-response relationship between exposures and outcomes was determined by restricted cubic splines (RCS) regression. Subgroup and mediation analyses were further conducted. Totally, 15,075 participants were enrolled in this study including 3,587 CRD patients. Compare with controls, CRD patients tended to be older, females and present higher SII and PhenoAgeAccel values. Single-index analysis indicated that either SII or PhenoAgeAccel demonstrated a significantly positive association with CRD via logistic regressions and RCS curves. Furthermore, the joint-indexes analysis revealed that compared to individuals with lower SII and PhenoAgeAccel, those with higher SII and PhenoAgeAccel exhibited remarkably stronger associations with CRD (adjusted OR [aOR], 1.56; 95% CI, 1.31–1.85; P < 0.001), chronic obstructive pulmonary disease (aOR, 1.56; 95% CI, 1.22-2.00; P = 0.001) and asthma (aOR, 1.40; 95% CI, 1.16–1.70; P = 0.001), which were predominant among those aged above 40 years, females and smokers. Eventually, mediation analyses suggested the mutual mediating effects of SII and PhenoAgeAccel on CRD and PhenoAgeAccel mediated SII resulting in CRD more significantly. This study confirmed the coexposure effect and mutual mediation between SII and PhenoAgeAccel on CRD. We recommend that the joint assessment may conduce to the accurate identification for populations susceptible to CRD and early prevention of chronic respiratory diseases.