Nanomicelle curcumin-induced testicular toxicity: Implications for altered mitochondrial biogenesis and mitophagy following redox imbalance.

The purpose of this study was to examine the effects of nano-micelle curcumin (NMC)-induced redox imbalance on mitochondrial biogenesis and mitophagy. For this purpose, 24 mature male Wistar rats were divided into control and NMC-received groups (7.5, 15, and 30 mg/kg) groups. After 48 days, the Nrf1, Nrf2, and SOD (Cu/Zn) expression levels, as well as GSH/GSSG, NADP+ /NADPH relative balances (elements involved in redox homeostasis) were analyzed. Moreover, to explore the effect of NMC on mitochondrial biogenesis, the expression levels of Mfn1, Mfn2, OPA1, Fis1, and Drp1 were investigated. Finally, the expression levels of Parkin/PARK and PINK (genes involved in mitochondrial quality control), as well as LC3-I/II (mitophagy marker), were analyzed. Observations showed that NMC, dose-dependently, altered GSH/GSSG, NADP+ /NADPH relative balances, suppressed SOD expression and diminished its biochemical level, and repressed Nrf1 and Nrf2 expression levels. Moreover, it could change the Mfn1, Mfn2, OPA1, Fis1, and Drp1 expression pattern and stimulate the Parkin/PARK and PINK as well as LC3-I/II expression levels, dose-dependently. In conclusion, chronic and high-dose NMC is able to suppress the redox capacity by down-regulating the Nrf1 and Nrf2 expression. Finally, at high-dose levels, it is able to trigger mitophagy signaling in the testicles.

A novel form of anti-angiogenic molecular antibody drug induces apoptosis in myeloma cells after cultivation upon endothelial feeder cells.

The present study aimed to investigate the ability of a novel form of the anti-angiogenic molecular antibody drug to induce Myeloma cell death after cultivation upon endothelial feeder cells. Bevacizumab-loaded chitosan (BCS) nanoparticles (NPs) were prepared by the ionic gelation method. Human U266 cell line and human umbilical vein endothelial cells were co-cultured for 72 h and treated with BCS nanoparticles (10µM) to study their impact on inhibition of cell growth and induction of apoptosis. Death assessments, P53 pro-apoptotic marker expression and the VEGF level were investigated by flow-cytometric analyses of the Annexin V, immunocytochemistry and ELISA, respectively. The endothelial monolayer co-culture showed protection of myeloma cells from apoptosis when exposed to NPs or without any treatment. In present of bevacizumab, the VEGF factor was effectively suppressed, and the p53 expression was significantly increased in bevacizumab-treated myeloma cells co-cultured with HUVECs, compared to other groups. BCS was capable of disturbing the effective interconnections of myeloma cells and HUVECs as supportive cells. Disruptions of tumor cells' connections with their microenvironment and blocking their possible supportive pathways might be a potential strategy to eradicate tumor cells and finally cure such types of cancer.

A 5-year Assessment on Carbon Monoxide Poisoning in a Referral Center in Tehran-Iran.

BACKGROUND: Carbon monoxide (CO) poisoning results in hundreds of deaths and thousands of emergency department visits all over Iran annually. In this study, we aim to provide an epidemiologic analysis of this poisoning in different consciousness levels. METHODS: This single-center retrospective study was conducted at a referral poison center from March 21, 2007 to March 19, 2012 in Tehran, Iran. All CO poisoned children and adults who hospitalized were evaluated based on their on-arrival consciousness level. RESULTS: Two-hundred-sixty patients with pure CO poisoning were enrolled with the majority of males (55.4%). CO exposure was unintentional in 99.6% of cases. The average period between CO exposure and the patients' hospital admission was 6.4 hours (SD = 11.2). Most of the toxicities had occurred at home (73.5%). On arrival acid-base status revealed respiratory acidosis cases in 11.9% of cases. Central nervous system imaging revealed 6.2% abnormal finding. Typically, patients presented with vomiting (25.8%), nausea (22.7%), and dizziness (11.3%). Twenty-nine patients (11.2%) needed intubation and mechanical ventilation. Thirty-six patients admitted to ICU with a median [IQR] hospital stay of 6 [2, 18] days. Ultimately, 202 (78.6%) patients discharged and 47 (18.3%) left the hospital against medical advice, 5 (1.9%) died, and 10 (3.8%) experienced sequellae. Two patients (0.8%), were transferred to other hospitals for specialized care. CONCLUSIONS: The incidence and mortality rate of CO poisoning in the current study are still higher than many other parts of the world. Ongoing health prevention strategies are not efficiently working. Hence, constant public education and warning about CO toxicity should be highlighted.