Fasting potentiates diclofenac-induced liver injury via inductions of oxidative/endoplasmic reticulum stresses and apoptosis, and inhibition of autophagy by depleting hepatic glutathione in mice.

Diclofenac, a widely used non-steroidal anti-inflammatory drug, can cause liver damage via its metabolic activation by hepatic CYP450s and UGT2B7. Fasting can affect drug-induced liver injury by modulating the hepatic metabolism, but its influence on diclofenac hepatotoxicity is unknown. Thus, we investigated diclofenac-induced liver damage after fasting in mice, and the cellular events were examined. Male ICR mice fasted for 16 h showed the elevation of CYP3A11, but the decreases of UGT2B7, glutathione (GSH), and GSH S-transferase-µ/-π levels in the livers. Diclofenac (200 mg/kg) injection into the mice after 16-h fasting caused more significant liver damage compared to that in the diclofenac-treated fed mice, as shown by the higher serum ALT and AST activities. Diclofenac-promoted hepatic oxidative stress (oxidized proteins, 4-hydroxynonenal, and malondialdehyde), endoplasmic reticulum (ER) stress (BiP, ATF6, and CHOP), and apoptosis (cleaved caspase-3 and cleaved PARP) were enhanced by fasting. Autophagic degradation was inhibited in the diclofenac-treated fasting mice compared to that of the corresponding fed mice. The results suggest that fasting can make the liver more susceptible to diclofenac toxicity by lowering GSH-mediated detoxification; increased oxidative/ER stresses and apoptosis and suppressed autophagic degradation may be the cellular mechanisms of the aggravated diclofenac hepatotoxicity under fasting conditions.

Consumer Acceptance of Texture-Modified Mackerel Stew Products in Older Adults.

Along with concerns regarding societal aging, the dietary requirements of older adults have become a priority. Older adults in Korea experience difficulties consuming animal protein sources as they age. Therefore, this study aimed to develop a senior-friendly food product using mackerel. Accordingly, carbohydrates and proteins were added to the brine solution before saturated vapor treatment. Calcium lactate and poly-gamma-glutamic acid were added to the sauce, and when compared to four commercial products (GT_R, GT_K, PC_K, and AC_G) in an acceptance test, the product was found to exhibit the highest overall liking score (p < 0.001). Higher flavor-liking and familiarity ratings were found to increase purchase intention, while higher flavor-liking, overall-liking, and familiarity ratings increased recommendation intention. Those in mid-to-late adulthood preferred the GT_R and PC_K samples, whereas the AC_G sample was preferred by those in very late adulthood. AC_G sample analysis suggested that those in the very late adulthood group had a relatively higher acceptance of spiciness. In this study, a calcium-added mackerel stew product was manufactured, meeting the standards for senior-friendly food in Korea. It will serve as a baseline for further research on fish- and mackerel-based foods for older adults, which is in its early stages.

Taurine Ameliorates Tunicamycin-Induced Liver Injury by Disrupting the Vicious Cycle between Oxidative Stress and Endoplasmic Reticulum Stress.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver dysfunction characterized by excess lipid accumulation; non-alcoholic steatohepatitis can transform into more severe conditions, such as cirrhosis and hepatocellular carcinoma. Although several pharmacologic approaches have been evaluated in clinical trials, there are no approved therapies for NAFLD. Previous studies have suggested that taurine supplementation alleviates fatty liver; however, the underlying mechanism remains obscure. In this study, we investigated the beneficial effects of taurine on fatty liver injury in vivo induced by tunicamycin, a chemical endoplasmic reticulum (ER) stressor. The mice were administered 2% taurine for 2 weeks prior to intraperitoneal tunicamycin injection; after 72 h of treatment, the mice were euthanized. Tunicamycin treatment significantly increased the levels of serum ALT and AST and hepatic triglycerides. Notably, these changes were alleviated by taurine supplementation. Taurine normalized the protein and/or mRNA levels involved in ER stress signaling (IRE1a, p-IRE1a, ATF6, XBP1, BiP, and CHOP) and lipid metabolism (CD36, MTTP, and ApoB), which were dysregulated by tunicamycin treatment. The stimulation of hepatic lipid export by taurine was evidenced by the recovery of blood VLDL levels. Furthermore, taurine supplementation prevented tunicamycin-induced lipid peroxidation and decreased glutathione (GSH) levels by correcting abnormal cysteine catabolism involved in the production of both taurine and GSH. Therefore, taurine supplementation can prevent tunicamycin-induced liver injury by counteracting oxidative and ER stress.

Factors influencing public health nurses' ethical sensitivity during the pandemic.

BACKGROUND: Ethical sensitivity is a prerequisite for ethical nursing practices. Efforts to improve nurses' ethical sensitivity are required to correctly recognise ethical conflicts and for sound decision-making. Because an emerging infectious disease response involves complex ethical issues, it is important to understand the factors that influence public health nurses' ethical sensitivity while caring for patients with COVID-19, an emerging infectious disease. OBJECTIVES: This study aims to identify the relationship between nursing professionalism, the organisation's ethical climate, and the ethical sensitivity of nurses who care for emerging infectious disease patients in Korean public health centres. Further, it sought to identify factors influencing ethical sensitivity and the mediating effect of the organisational ethical climate to inform guidelines and improve ethical sensitivity. RESEARCH DESIGN: This was a cross-sectional descriptive study. PARTICIPANTS AND RESEARCH CONTEXT: Data were collected from February 3 to 8 March 2021. Participants included 167 nurses caring for patients with COVID-19 in public health centres in South Korea. ETHICAL CONSIDERATION: This study was approved by the Institutional Review Board of the Chung-Ang University and followed the principles of research ethics. RESULTS: The factors influencing ethical sensitivity were working at a COVID-19 disease direct response department, nursing professionalism, and organisation's ethical climate. The organisation's ethical climate showed a partial mediating effect on the influence of nursing professionalism on ethical sensitivity. CONCLUSION: Our findings show that nurses' ethical sensitivity can be improved by refining the organisation's ethical climate and nursing professionalism.

Investigation of the Effect of 3D Meniscus Geometry on Fluid Dynamics and Crystallization via In Situ Optical Microscopy-Assisted Mathematical Modeling.

Solution-based thin-film solidification is a complex process involving various transport phenomena that are intricately dependent on multiple experimental parameters. The difficulty of analyzing this process experimentally or conducting exact numerical simulation make it challenging to understand, predict, and control the solidification process. In this work, a simple and effective technique to analyze the thin-film solidification process during solution shearing, based on 3D geometrical model of the meniscus, is proposed. The 3D meniscus geometry, which changes depending on the experimental parameters, is attained using high-speed side-view and top-view in situ microscopy. Thereafter, mass and momentum transport mathematical models are applied to obtain numerical solutions of transport phenomena within the meniscus. Utilizing these results, the underlying mechanism of dendritic growth of small molecule organic semiconductor is elucidated, which has previously been unknown. The 3D meniscus modeling is particularly important for this analysis, as dendrite formation is strongly dependent on the meniscus geometry near the contact line and mass transport variation perpendicular to the coating direction. This technique enables the study of complex relationship between experimental parameters and solidification process, which is widely applicable to various materials and coating systems; whereby, better understanding of thin-film growth and device performance optimization is possible.

Downregulation of Glutathione-Mediated Detoxification Capacity by Binge Drinking Aggravates Acetaminophen-Induced Liver Injury through IRE1α ER Stress Signaling.

Overdose of acetaminophen (APAP) can cause severe liver injury. Although alcohol is considered a risk factor for APAP toxicity, the mechanism underlying the interaction between alcohol and APAP remains unclear. Binge alcohol (5 g/kg every 12 h, 3 doses) reduced the concentration of cysteine and glutathione (GSH) and decreased expression of cystathionine ß-synthase (CßS), cystathionine γ-lyase (CγL), and glutamate cysteine ligase catalytic subunit (GCLC) in the livers of male C57BL/6 mice. Furthermore, the levels of GSH S-transferase (GST) and GSH peroxidase (GPx) were decreased. To evaluate the effect of binge drinking on APAP-induced liver injury, 300 mg APAP was administered following alcohol binges. APAP in the binge group significantly amplified the serum ALT more than two fold and enhanced the pro-apoptotic proteins with a severe centrilobular necrosis compared to APAP alone. APAP treatment after alcohol binges caused lower levels of hepatic cysteine and GSH than APAP alone over 24 h, indicating that alcohol binges reduced GSH regenerating potential. Exposure to APAP after binge treatment significantly increased oxidative stress (lipid peroxidation) and endoplasmic reticulum (ER) stress (Grp78 and ATF6) markers at 6 h after treatment. Notably, the IRE1α/ASK1/MKK4/JNK pathway was activated, whereas CHOP expression was reduced by APAP administration in mice with pre-exposed alcohol binges compared with APAP alone. Thus, pretreatment with binge alcohol decreases GSH-mediated antioxidant capacity and contributes to augmentation of liver injury caused by subsequent APAP administration through differential ER stress signaling pathway.