Jaintran2774

Dysregulation in mitochondrial dynamics has been associated with several diseases including cancer. Present study assessed the alteration in mitochondrial fission protein (Drp1) in oral epithelial cells collected from clinically confirmed pre-cancer and cancer patients and further correlates it with the cellular apoptosis signaling. Results indicate the ROS accumulation in OSCC patients is accompanied by several changes including increase in mitochondrial mass, expression of mitochondrial fission protein (Drp1) and alteration in apoptotic signaling. The positive co-relation has been observed between the expressions of anti-apoptotic Bcl-2proteinswith mitochondrial fission protein Drp1. Higher mitochondrial fission in oral cancer cells was also correlated with the increased expression of cell cycle marker CyclinD1 indicating highly proliferative stage of oral cancer cells. The clinical correlation can be extended to develop biomarker for diagram and program in oral cancer management. Activating type 1 cannabinoid (CB1) receptor decreases the particle size of high-density lipoprotein (HDL) and inhibits reverse cholesterol transport (RCT). This study examined whether marijuana (MJ) use is associated with changes of RCT, and how the latter is associated with mitochondrial function and fluid cognition. We recruited 19 chronic MJ users and 20 nonusers with matched age, BMI, sex, ethnicity, and education. We measured their fluid cognition, mitochondrial function (basal and max respiration, ATP production) in peripheral blood mononuclear cells, cholesterol content in serum lipoprotein fractions, enterolactone/creatinine ratio in urine as a marker for dietary polyphenol intake, and lipase activity in serum. We found that higher percentage of large HDL cholesterol (HDL-C) correlated positively, while that of small HDL-C correlated inversely, with mitochondrial function among MJ users, but correlations of the opposite directions were found among nonusers. The concentrations of large and intermediate HDL-C correlated positively with mitochondrial function and fluid cognition among MJ users, but not among nonusers. Both percentage and concentration of large HDL-C correlated positively, while those of small HDL-C correlated inversely, with amounts of daily and lifetime MJ use. In all participants, higher urinary enterolactone/creatinine ratio and lower serum lipase activity were associated with higher large HDL-C/small HDL-C ratio, implying greater RCT. This study suggests that high MJ use may compromise RCT, which is strongly associated with mitochondrial function and fluid cognition among MJ users. BACKGROUND & AIM Acute liver injury (ALI) can occur if a significant acetaminophen (APAP) overdose presents too late for n-acetylcysteine treatment, which risks deterioration into acute liver failure, systemic inflammation, and death. Macrophages influence the progression and resolution of ALI due to their innate immunological function and paracrine activity. Syngeneic primary bone-marrow derived macrophages (BMDMs) were tested as a cell-based therapy in a mouse model of APAP-ALI METHODS Several phenotypically-distinct BMDM populations were delivered intravenously to APAP-ALI mice when hepatic necrosis was established, and then evaluated based on their effects on injury, inflammation, immunity, and regeneration. In vivo phagocytosis assays were used to interrogate the phenotype and function of alternatively-activated BMDMs (AAMs) post-injection. Finally, primary human AAMs sourced from healthy volunteers were evaluated in immunocompetent APAP-ALI mice. RESULTS BMDMs rapidly localised in liver and spleen within four hours of administration. buy A1874 Injection of AAMs specifically reduced hepatocellular necrosis, HMGB1 translocation, and infiltrating neutrophils following APAP-ALI. AAM delivery also stimulated proliferation in hepatocytes and endothelium, and reduced levels of several circulating proinflammatory cytokines within 24 hours. AAMs displayed a high phagocytic activity both in vitro and in injured liver tissue post-injection. Crosstalk with the host innate immune system was evidenced by reduced infiltrating host Ly6Chi macrophages in AAM-treated mice. Importantly, therapeutic efficacy was partially recapitulated using clinical-grade primary human AAMs in immunocompetent APAP-ALI mice underscoring translational potential CONCLUSION We identify that AAMs have value as a cell-based therapy in an experimental model of APAP-ALI. Human AAMs warrant further evaluation as a potential cell-based therapy for APAP overdose patients with established liver injury. V.BACKGROUND The reliability of somatosensory evoked potential (SSEP) to predict a poor outcome of cardiac arrest patients after targeted temperature management (TTM) has been questioned due to self-fulfilling prophecy. METHODS This was a multicentre, prospective, registry-based study. Data were collected from the Korean Hypothermia Network (KORHN)-pro registry between November 2015 and December 2018. We excluded cases with possible bias (inappropriate SSEP recordings and patients who decided on the withdrawal of life-sustaining therapy [WLST]) and calculated the sensitivities and false positive rates (FPRs) for an absent N20 and an absent brainstem reflex. A poor outcome was defined as a cerebral performance category score of 3-5 after 6 months. RESULTS A total of 262 patients were analysed 83 in the good outcome group and 179 in the poor outcome group. A bilaterally absent N20 was found in 127 patients and predicted a poor outcome with a sensitivity of 71.0% (95% confidence interval [CI], 63.7-77.5) and an FPR of 0.0% (95% CI, 0.0-4.3). Among the patients with absent brainstem reflexes (n = 103), 3 had a good outcome, with an FPR of 4.3% (95% CI, 0.9-12.2). The absence of one or both N20 and brainstem reflex had a sensitivity of 84.2% (95% CI, 77.4-89.6) and an FPR of 4.3% (95% CI, 0.9-12.2). CONCLUSIONS Our results provide further evidence that SSEP exactly predicts poor neurological outcome in these patients and suggest that caution be taken when the brainstem reflex is used as a single test to make decisions regarding WLST. V.