Curcumin Prevents Epithelial-to Mesenchymal Transition-Mediated Ovarian Cancer Progression through NRF2/ETBR/ET-1 Axis and Preserves Mitochondria Biogenesis in Kidney after Cisplatin Administration.

Purpose: Ovarian carcinoma is one of the gynaecological malignancies that have the highest mortality rates due to its progressivity. Endothelin signalling plays a leading role in the progression of ovarian cancer through Epithelial-to-Mesenchymal Transition (EMT). Cisplatin commonly used as potent chemotherapy; however, its application hindered by its nephrotoxic effect. Curcumin, a turmeric-derived compound, has an anticancer property, as well as a renal protective effect. Moreover, curcumin augments the affinity of the antioxidant enzyme, while inhibits endothelin-1 (ET-1) signalling. The effects of curcumin on ovarian cancer progression and cisplatin-induced kidney injury remain unknown. Methods: Curcumin was used as a supplementary therapy together with cisplatin in Human Ovarian Cancer Cell line (SKOV3) and also in rodent-induced ovarian cancer. The kidney phenotype in the ovarian cancer rat model after cisplatin ± curcumin administration will also be analyzed Results: Co-treatment of cisplatin with curcumin enhanced the expression of a gene involved in apoptosis in association with NRF2 enhancement, thus activated ETBR-mediated ET-1 clearance in SKOV3 cell and ovarian cancer model in rat. Moreover, curcumin treatment improved mitochondria biogenesis markers such as PGC-1α and TFAM and prevented the elevated of ET-1-mediated renal fibrosis and apoptosis in kidney isolated from cisplatin-treated ovarian cancer rat. Conclusion: Curcumin could be potentially added as an anticancer adjuvant with protective effects in the kidney; thus, improves the efficacy and safety of cisplatin treatment in the clinical setting.

Transport viable heart tissue at physiological temperature yielded higher human cardiomyocytes compared to the conventional temperature.

This study investigated the optimum transport condition for heart tissue to recover single-cell cardiomyocytes for future in-vitro or in-vivo studies. The heart tissues were obtained from removing excessive myocardium discharged during the repair surgery of an excessive right atrial hypertrophy due to a congenital disease. The transportation temperature studied was the most used temperature (4 °C) or the conventional condition, compared to a physiological temperature(37 °C). The heart tissues were transported from the operating theatre to the lab maintained less than 30 min consistently. Single-cell isolation was enzymatically and mechanically performed using collagenase-V (160 U/mg) and proteinase-XXIV (7-14 U/mg) following the previously described protocol. The impact of temperature differences was observed by the density of cells harvested per mg tissue, cell viability, and the senescence signals, identified by the p21, p53 and caspase-9 mRNA expressions. Results the heart tissue transported at 37 °C yielded significantly higher viable cell density (p < 0.01) yielded viable cells significantly higher density (p < 0.01) than the 4 °C; 2,335 ± 849 cells per mg tissue, and 732 ± 425 cells per mg tissue, respectively. The percentage of viable cells in both groups showed no difference. Although the 37 °C group expressed the apoptosis genes such as p21, p53 and caspase9 by 2.5-, 5.41-, 5-fold respectively (p > 0.05). Nonetheless, the Nk×2.5 and MHC genes were expressed 1,7- and 3.56-fold higher than the 4 °C. and the c-Kit+ expression was 17.56-fold, however, statistically insignificant. Conclusion When needed for single-cell isolation, a heart tissue transported at 37 °C yielded higher cell density per mg tissue compared to at 4 °C, while other indicators of gene expressions for apoptosis, cardiac structural proteins, cardiac progenitor cells showed no difference. Further investigations of the isolated cells at different temperature conditions towards their proliferation and differentiation capacities in a 3-D scaffold would be essential.

Preparation of Cell-Seeded Heart Patch In Vitro; Co-Culture of Adipose-Derived Mesenchymal Stem Cell and Cardiomyocytes in Amnion Bilayer Patch.

INTRODUCTION: Cardiovascular disease is the second killer across the globe, while coronary disease is the major cause. Cell therapy is one alternative to regenerate the infarcted heart wall. MATERIALS AND METHODS: In this study, the cardiomyogenesis capacity of human adipose stem cells (hAdSC) and human cardiomyocytes (hCardio) cultured in a 3-D biological scaffold (decellularised amnion bilayer) for nine days in a static condition was investigated. The cardiomyogenesis capacity of hAdSC were identified using immunohistochemistry and RT-PCR. The population of the cells isolated from the heart tissue expressed cTnT-1 (13.38 ± 11.38%), cKit (7.85 ± 4.2%), ICAM (85.53 ± 8.69%), PECAM (61.63 ± 7.18%) and VCAM (35.9 ± 9.11%), while from the fat tissue expressed the mesenchymal phenotypes (CD73, CD90, CD105, but not CD45, CD34, CD11b, CD19 and HLA-DR). Two age groups of hAdSC donors were compared, the youngsters (30-40yo) and the elderly (60-70 yo). RESULTS: The co-culture showed that after 5-day incubation, the seeded graft in the hAdSC-30 group had a tube-like appearance while the hAdSC-60 group demonstrated a disorganised pattern, despite of the MSC expressions of the hAdSC-60 were significantly higher. Initial co-culture showed no difference of ATP counts among all groups, however the hAdSC-30 group had the highest ATP count after 9 days culture (p = 0.004). After normalising to the normal myocardium, only the hAdSC-60 group expressed cTnT and MHC, very low, seen during the initial cultivation, but then disappeared. Meanwhile, the hAdSC-30 group expressed α-actinin, MHC and cTnT in the Day-5. The PPAR also was higher in the Day-5 compared to the Day-9 (p < 0.005). CONCLUSION: Cardiomyogenesis capacity of hAdSC co-cultured with hCardio in a 3-D scaffold taken from the 30-40yo donor showed better morphology and viability than the 60-70yo group, but maintained less than 5 days in this system.