Grahambender5103

BACKGROUND Induced pluripotent stem cells (iPSCs) exhibit limitless pluripotent plasticity and proliferation capability to provide an abundant cell source for tissue regenerative medicine. Thus, inducing iPSCs toward a specific differentiation direction is an important scientific question. Traditionally, iPSCs have been induced to chondrocytes with the help of some small molecules within 21-36 days. To speed up the differentiation of iPSCs, we supposed to utilize bioactive ceramics to assist chondrogenic-induction process. METHODS In this study, we applied ionic products (3.125~12.5 mg/mL) of the lithium-containing bioceramic (Li2Ca4Si4O13, L2C4S4) and individual Li+ (5.78~23.73 mg/L) in the direct chondrogenic differentiation of human iPSCs. RESULTS Compared to pure chondrogenic medium and extracts of tricalcium phosphate (TCP), the extracts of L2C4S4 at a certain concentration range (3.125~12.5 mg/mL) significantly enhanced chondrogenic proteins Type II Collagen (COL II)/Aggrecan/ SRY-Box 9 (SOX9) synthesis and reduced hypertrophic protein type X collagen (COL X)/matrix metallopeptidase 13 (MMP13) production in iPSCs-derived chondrocytes within 14 days, suggesting that these newly generated chondrocytes exhibited favorable chondrocytes characteristics and maintained a low-hypertrophy state. Further studies demonstrated that the individual Li+ ions at the concentration range of 5.78~23.73 mg/L also accelerated the chondrogenic differentiation of iPSCs, indicating that Li+ ions played a pivotal role in chondrogenic differentiation process. CONCLUSIONS These findings indicated that lithium-containing bioceramic with bioactive specific ionic components may be used for a promising platform for inducing iPSCs toward chondrogenic differentiation and cartilage regeneration.BACKGROUND Human-induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have shed great light on cardiac regenerative medicine and specifically myocardial repair in heart failure patients. However, the treatment efficacy and the survival of iPSC-CMs in vivo after transplantation have yielded inconsistent results. OBJECTIVES The objective of this study was to evaluate the ability of human iPSC-CMs to improve myocardial function in a rat postinfarction heart failure model. METHODS Eight-week-old male Sprague-Dawley rats were randomly selected to receive an intramyocardial injection of 5% albumin solution with or without 1 × 107 human iPSC-CMs 10 days after undergoing left anterior descending (LAD) coronary artery ligation. Cyclosporine A and methylprednisolone were administered before iPSC-CM injection and until the rats were killed to prevent graft rejection. Cardiac function was evaluated by echocardiography. The survival of grafted cardiomyocytes was confirmed by observing the fluorescent cell trace.54%). Cell labeling, tracking, and molecular biology techniques indicated that the grafted cardiomyocytes survived in the rat heart 1 month after iPSC-CM transplantation. Myocardial fibrosis was also attenuated in the iPSC-CM treatment group. CONCLUSIONS Human iPSC-CM grafts survived in infarcted rat hearts and restored myocardial function 4 weeks after transplantation. Cell replacement therapy also reversed ventricular remodeling, indicating the potential of iPSC-CMs for cardiac repair strategies.Trichinellosis, which is caused by Trichinella spiralis (T. spiralis), is a serious zoonosis. Pigs play an important role in the transmission of human trichinellosis. MPP antagonist manufacturer Characterizing the immune response to T. spiralis infection is key to elucidating host-parasite interactions. However, most studies on the immune response to T. spiralis infection have employed murine models. In this study, we investigated the immune response to T. spiralis infection in pigs. The results showed that the average numbers of larvae per gram (lpg) for the 100-muscle larvae (ML), 1000-ML, and 10 000-ML groups were 1.502, 35.947, and 398.811, respectively. The percentages of CD3+ T cells, B cells, CD4+ T cells, Treg cells, and Th17 cells were elevated in the infection groups compared to the control animals. In contrast, CD8+ T cell percentages were reduced after infection in the low-dose group. The number of neutrophils was increased at 3-17 days post-infection (dpi). Th1 cytokine IL-2 levels were significantly decreased at 7 dpi, and Th2 cytokine IL-4 levels were significantly elevated at 3 dpi. Treg cytokine IL-10 levels were significantly elevated between 7 dpi and 30 dpi. Th17 cytokine IL-17A levels were significantly increased beginning at 11 dpi. These results confirmed that pigs infected with T. spiralis predominantly induced Th2 and Treg immune responses, which suppress the Th1 immune responses. This study provides novel insights into the immune response of pigs infected with T. spiralis.BACKGROUND Emerging data points to a potential heroin use epidemic in South Africa. Despite this, access to methadone maintenance therapy and other evidence-based treatment options remains negligible. We aimed to assess retention, changes in substance use and quality of life after 6 months on methadone maintenance therapy provided through a low-threshold service in Durban, South Africa. METHODS We enrolled a cohort of 54 people with an opioid use disorder into the study. We reviewed and described baseline socio-demographic characteristics. Baseline and 6-month substance use was assessed using the World Health Organization's Alcohol Smoking and Substance Use Involvement Screening Test (ASSIST) and quality of life, using the SF-12. We compared changes at 6 months on methadone to baseline using the Wilcoxon signed rank test and paired-tests for the ASSIST and SF-12 scores, respectively. McNemar's test was used for comparisons between paired results of categorical variables relating to injecting frequency. RESULTS The majority of the participants were young, Black African males, with a history of drug use spanning over 10 years. Retention after 6 months was 81%. After 6 months, the median heroin ASSIST score decreased from 37 to 9 (p  less then  0.0001) and the cannabis ASSIST score increased from 12.5 to 21 (p = 0.0003). The median mental health composite score of the SF-12 increased from 41.4 to 48.7 (p = 0.0254). CONCLUSIONS Interim findings suggest high retention, significant reductions in heroin use and improvements in mental health among participants retained on methadone maintenance therapy for 6 months. Further research into longer term outcomes and the reasons contributing to these changes would strengthen recommendations for the scale-up of methadone maintenance therapy in South Africa.