Oncogenic K-ras Induces Mitochondrial OPA3 Expression to Promote Energy Metabolism in Pancreatic Cancer Cells

K-ras (Kirsten ras GTPase) mutations are oncogenic events frequently observed in many cancer types especially in pancreatic cancer. Although mitochondrial dysfunction has been associated with K-ras mutation, the molecular mechanisms by which K-ras impacts mitochondria and maintains metabolic homeostasis are not fully understood. In this study, we used two K-ras inducible cell systems, human pancreatic epithelial/ K-rasG12D (HPNE/K-rasG12D) and human embryonic kidney cells with tetracycline repressorT-Rex/K-rasG12V, to evaluate the role of oncogenic K-ras in regulating mitochondrial function. Among a panel of genes known to affect mitochondria, only the expression of OPA3 (optic atrophy protein 3) was consistently up-regulated by K-ras activation in both cell lines. Importantly, high expression of OPA3 was also observed in clinical pancreatic cancer tissues. Genetic knockdown of OPA3 caused a significant decrease of energy metabolism, manifested by a suppression of oxygen consumption rate (OCR) and a decrease in cellular ATP content, leading to inhibition of cell proliferation capacity and reduced expression of epithelial–mesenchymal transition (EMT) markers. Our study suggests that OPA3 may promote cellular energy metabolism and its up-regulation in K-ras-driven cancer is likely a mechanism to offset the negative impact of K-ras on mitochondria to maintain energy homeostasis. As such, OPA3 could be a potential target to kill cancer cells with K-ras mutations

Effects of Different Hormone Treatments on Germination of Nicandra physaloides Seeds

【Objective】The seed germination of Nicandra physaloides was seriously affected by external colloid. The study was conducted in order to explore the effects of different hormone treatments on germination of N. physaloides seeds and increase the seed germination rate.【Method】The seeds of N. physaloides were used as test materials, and the random block method was used to set 4 ℃ low temperature treatment with seeds put on gauze and MS medium treatments of gibberellin (GA3), 6-benzylaminopurine (6-BA) and naphthylacetic acid (NAA), and the results of the four treatments were regularly observed and recorded.【Result】Compared with the normal temperature control, low temperature treatment at 4 ℃ on gauze significantly promoted the germination of N. physaloides seeds, and the highest germination rate was 25% after 48 h of treatment. The germination rate and germination index of N. physaloides seeds treated with 10 mg/L GA3 were 92.00% and 9.58, which were 4.27% and 1.33 higher than those of CK, respectively. The germination rate of the seeds treated with 1 mg/L 6-BA was the highest as 96.63%, and the germination potential of the seeds treated with 2 mg/L 6-BA was the highest as 73.33%, which were 8.9% and 10.07% higher than those of CK, respectively. The germination rate of the seeds treated with 1 and 2 mg/L NAA was 88.86%, but both the germination potential and germination index were lower than CK. Compared with CK, 10 and 50 mg/L GA3 treatment significantly increased hypocotyl length, while 6-BA and NAA treatments significantly decreased hypocotyl length.【Conclusion】Low temperature treatment can significantly promote the germination of N. physaloides seeds, and low concentration hormone treatment on MS medium can improve the germination rate of N. physaloides seeds. Through comprehensive comparison of germination rate, germination potential, germination index and hypocotyl length, the best hormone treatment for N. physaloides seeds is MS + 10 mg/L GA3

Prospective study on the clinical and economic burden of venous leg ulcers in the tropics

Objective: Venous leg ulcers (VLUs) are both chronic and recurrent. The treatment of such ulcers often require multiple outpatient visits and dressing changes. Several reports on the costs of treating such VLUs have been reported in the west. We prospectively evaluated the clinical and economic burden of VLUs in a population of Asian patients in the tropics. Methods: Patients from a prospective two-center study conducted at two tertiary hospitals in Singapore, as a part of the Wound Care Innovation in the Tropics program, between August 2018 and September 2021 were recruited. The patients were followed up for 12 weeks (visit 1 to visit 12), until index ulcer healing, death, or lost to follow-up (whichever came first). These patients were then followed up 12 weeks later to determine the longer term outcome of the wound (healed, recurrence, remained unhealed). The itemized costs derived from the medical service were retrieved from the relevant departments of the study sites. The patients' health-related quality of life was assessed at baseline and the last visit of the 12-week follow-up period (or until index ulcer healing), using the official Singapore version of the EuroQol five-dimension-5L questionnaire, which also includes a visual analog scale (EQ-VAS). Results: A total of 116 patients were enrolled; 63% were men, and the mean patient age was 64.7 years. Of the 116 patients, 85 (73%) had a healed ulcer at 24 weeks (mean duration to ulcer healing, 49 days), and 11 (12.9%) had experienced ulcer recurrence within the study period. Within the 6-month follow-up period, the mean direct healthcare cost per patient was USD$1998. The patients with healed ulcers had significantly lower costs per patient compared with those with unhealed ulcers (USD$1713 vs USD$2780). Regarding health-related quality of life, 71% of the patients had a lower quality of life at baseline, which had improved at 12 weeks of follow-up, with only 58% of the patients reported to have a lower quality of life. Also, the patients with healed ulcers scored higher for both utilities (societal preference weights) and EQ-VAS at follow-up (P [removed]Agency for Science, Technology and Research (A*STAR)The present study was supported by the Industry Alignment Fund – Pre-Positioning Programme from the Agency for Science, Technology and Research (grant H18/01/a0/ZZ9)