3D-bioprinted GelMA/gelatin/amniotic membrane extract (AME) scaffold loaded with keratinocytes, fibroblasts, and endothelial cells for skin tissue engineering.

Gelatin-methacryloyl (GelMA) is a highly adaptable biomaterial extensively utilized in skin regeneration applications. However, it is frequently imperative to enhance its physical and biological qualities by including supplementary substances in its composition. The purpose of this study was to fabricate and characterize a bi-layered GelMA-gelatin scaffold using 3D bioprinting. The upper section of the scaffold was encompassed with keratinocytes to simulate the epidermis, while the lower section included fibroblasts and HUVEC cells to mimic the dermis. A further step involved the addition of amniotic membrane extract (AME) to the scaffold in order to promote angiogenesis. The incorporation of gelatin into GelMA was found to enhance its stability and mechanical qualities. While the Alamar blue test demonstrated that a high concentration of GelMA (20%) resulted in a decrease in cell viability, the live/dead cell staining revealed that incorporation of AME increased the quantity of viable HUVECs. Further, gelatin upregulated the expression of KRT10 in keratinocytes and VIM in fibroblasts. Additionally, the histological staining results demonstrated the formation of well-defined skin layers and the creation of extracellular matrix (ECM) in GelMA/gelatin hydrogels during a 14-day culture period. Our study showed that a 3D-bioprinted composite scaffold comprising GelMA, gelatin, and AME can be used to regenerate skin tissues.

Exploring the various effects of Cu doping in hydroxyapatite nanoparticle.

Adding foreign ions to hydroxyapatite (HAp) is a popular approach for improving its properties. This study focuses on the effects of calcium substitution with copper in HAp. Instead of calcium, copper ions were doped into the structure of hydroxyapatite nanoparticles at 1%, 3%, and 5% concentrations. XRD analysis showed that the amount of substituted copper was less than needed to generate a distinct phase, yet its lattice parameters and crystallinity slightly decreased. Further, the results of degradation tests revealed that copper doping in hydroxyapatite doubled calcium ion release in water. The incorporation of copper into the apatite structure also boosted the HAp zeta potential and FBS protein adsorption onto powders. According to antibacterial investigations, a concentration of 200 mg/ml of hydroxyapatite containing 5% copper was sufficient to effectively eradicate E. coli and S. aureus bacteria. Furthermore, copper improved hydroxyapatite biocompatibility. Alkaline phosphatase activity and alizarin red tests showed that copper in hydroxyapatite did not inhibit stem cell differentiation into osteoblasts. Also, the scratch test demonstrated that copper-containing hydroxyapatite extract increased HUVEC cell migration. Overall, our findings demonstrated the utility of incorporating copper into the structure of hydroxyapatite from several perspectives, including the induction of antibacterial characteristics, biocompatibility, and angiogenesis.

Platelet distribution widths and white blood cell are associated with cardiovascular diseases: data mining approaches.

OBJECTIVE: To investigate the association between cardiovascular diseases (CVDs) and haematologic factors in a cohort of Iranian adults. METHOD: For a total population of 9,704 aged 35 to 65, a prospective study was designed. Haematologic factors and demographic characteristics (such as gender, age, and smoking status) were completed for all participants. The association between haematologic factors and CVDs was assessed through logistic regression (LR) analysis, decision tree (DT), and bootstrap forest (BF). RESULTS: Almost all of the included factors were significantly associated with CVD (p<.001). Among the included factors, were: age, white blood cell (WBC), and platelet distribution width (PDW) had the strongest correlation with the development of CVD. For unit OR interpretation, WBC has been represented as the most remarkable risk factor for CVD (OR: 1.22 (CI 95% (1.18, 1.27))). Also, age is associated with an increase in the odds of CVD + occurrence (OR: 1.12 (CI 95% (1.11, 1.13))). Moreover, males are times more likely to develop CVD than females (OR: 1.39 (CI 95% (1.22, 1.58))). In DT model, age is the best classifier factor in CVD development, followed by WBC and PDW. Furthermore, based on the BF algorithm, the most crucial factors correlated with CVD are age, WBC, PDW, sex, and smoking status. CONCLUSION: The obtained result from LR, DT, and BF models confirmed that age, WBC, and PDW are the most crucial factors for the development of CVD.

Development of Data Mining Algorithms for Identifying the Best Anthropometric Predictors for Cardiovascular Disease: MASHAD Cohort Study.

INTRODUCTION: Many studies have been published to assess the best anthropometric measurements associated with cardiovascular diseases (CVDs), but controversies still exist. AIM: Investigating the association between CVDs and anthropometric measurements among Iranian adults. METHODS: For a total population of 9354 aged 35 to 65, a prospective study was designed. Anthropometric measurements including ABSI (A Body Shape Index), Body Adiposity Index (BAI), Body Mass Index (BMI), Waist to Height Ratio (WHtR), Body Round Index (BRI), HC (Hip Circumference), Demispan, Mid-arm circumference (MAC), Waist-to-hip (WH) and Waist Circumference (WC) were completed. The association between these parameters and CVDs were assessed through logistic regression (LR) and decision tree (DT) models. RESULTS: During the 6-year follow-up, 4596 individuals (49%) developed CVDs. According to the LR, age, BAI, BMI, Demispan, and BRI, in male and age, WC, BMI, and BAI in female had a significant association with CVDs (p-value < 0.03). Age and BRI for male and age and BMI for female represent the most appropriate estimates for CVDs (OR: 1.07, (95% CI: 1.06, 1.08), 1.36 (1.22, 1.51), 1.14 (1.13, 1.15), and 1.05 (1.02, 1.07), respectively). In the DT for male, those with BRI ≥ 3.87, age ≥ 46 years, and BMI ≥ 35.97 had the highest risk to develop CVDs (90%). Also, in the DT for female, those with age ≥ 54 years and WC ≥ 84 had the highest risk to develop CVDs (71%). CONCLUSION: BRI and age in male and age and BMI in female had the greatest association with CVDs. Also, BRI and BMI was the strongest indices for this prediction.

Synergy effects of copper and L-arginine on osteogenic, angiogenic, and antibacterial activities.

Copper (Cu) ions have been found to exert antibacterial and angiogenic effects. However, some studies have indicated that it inhibits osteogenesis at high concentrations. On the other hand, L-arginine (Arg) is a semi-essential amino acid required for various biological processes, including osteogenic and angiogenic activities. As a result, we hypothesized that combining Arg with Cu ions would reduce its inhibitory effects on osteogenesis while increasing its angiogenic and antibacterial capabilities. To assess osteogenic and angiogenic activities, we employed rat bone marrow mesenchymal stem cells (MSCs) and human umbilical vein endothelial cells (HUVECs), respectively. The gram-positive bacteria Staphylococcus epidermidis (S. epidermidis), Staphylococcus aureus (S. aureus), and the gram-negative bacterium Escherichia coli (E. coli) were used to investigate bacterial behaviors. According to ALP activity and calcium deposition outcomes, copper ions inhibited osteogenic development of MSCs at 100 µM; however, Arg supplementation somewhat mitigated the inhibitory effects. Furthermore, Copper and Arg synergistically stimulated migration and tube formation of HUVECs. According to our findings, copper ions and Arg in the range of 1-100 µM had no antibacterial effect on any examined bacteria. However, at a dose of 20 mM, copper demonstrated antibacterial activity, which was boosted by Arg. Overall, these findings suggest that a combination of copper and Arg may be more beneficial for bone regeneration than either copper or Arg alone.

Regenerative Medicine in COVID-19 Treatment: Real Opportunities and Range of Promises.

Novel coronavirus disease (COVID-19) has attracted much attention around the world due to its rapid transmission among humans and relatively high mortality rate. Studies are increasing to find the best therapeutic approach for the disease and its management. Regenerative medicine offers various cell-tissue therapeutics and related products, such as stem cell therapy, natural killer (NK) cell therapy, Chimeric antigen receptor (CAR) T cell therapy, exosomes, and tissue products. Interestingly, mesenchymal stem cells (MSCs) can reduce inflammatory symptoms and protect against cytokine storm, which critically contributes to the COVID-19 progression. Notably, having the potentials to exert cytotoxic effects on infected cells and induce interferon production probably make NK cells a candidate for COVID-19 cell therapy. Besides, exosomes are one of the crucial products of cells that can exert therapeutic effects through the induction of immune responses and neutralizing antibody titers. The paper aims to briefly consider current options for COVID-19 therapy to show that there is no specific cure for COVID-19, and then assess the real opportunities and range of promises regenerative medicine can provide for specific treatment of COVID-19. Graphical Abstract Therapeutic Potential of Regenerative Medicine against COVID19.