Hepatotoxic of polystyrene microplastics in aged mice: Focus on the role of gastrointestinal transformation and AMPK/FoxO pathway.

Microplastic (MP) toxicity has attracted widespread attention, whereas before triggering hepatotoxicity, ingested MPs first undergo transportation and digestion processes in the gastrointestinal tract, possibly interacting with the gastrointestinal contents (GIC). More alarming is the need for more understanding of how this process may impact the liver health of aged animals. This study selected old mice. Firstly, we incubated polystyrene microplastics (PS-MPs, 1 µm) with GIC extract. The results of SEM/EDS indicated a structural alteration in PS-MPs. Additionally, impurities resembling corona, rich in heteroatoms (O, N, and S), were observed. This resulted in an enhanced aggregating phenomenon of MPs. We conducted a 10-day experiment exposing aged mice to four concentrations of PS-MPs, ranging from 1 × 103 to 1 × 1012 particles/L. Subsequent measurements of tissue pathology and body and organ weights were conducted, revealing alterations in liver structure. In the liver, 12 crucial metabolites were found by LC-MS technology, including purines, lipids, and amino acids. The AMPK/FoxO pathway was enriched, activated, and validated in western blotting results. We also comprehensively examined the innate immune system, inflammatory factors, and oxidative stress indicators. The results indicated decreased C3 levels, stable C4 levels, inflammatory factors (IL-6 and IL-8), and antioxidant enzymes were increased to varying degrees. PS-MPs also caused DNA oxidative damage. These toxic effects exhibited a specific dose dependence. Overall, after the formation of the gastrointestinal corona, PS-MPs subsequently impact various cellular processes, such as cycle arrest (p21), leading to hepatic and health crises in the elderly. The presence of gastrointestinal coronas also underscores the MPs' morphology and characteristics, which should be distinguished after ingestion.

Hearing loss, depression and social participation of older adults: Evidence from the China health and retirement longitudinal study.

AIM: Hearing loss and depression in older adults are associated with a lower social participation rate. However, few studies have thoroughly analyzed the relationship between them. METHODS: The data were obtained from the China Health and Retirement Longitudinal Study carried out in 2011, 2013 and 2015, and data from 24 306 participants ranging in age from 50 to 80 years were used in this study. Hearing loss, depression and social participation were assessed by self-reported hearing status, the 10-item Center for the Epidemiological Studies of Depression Short Form, and self-reported social participation activity types and frequency. The fixed effects logistic regression and random effects logistic regression were used to examine the relationship between hearing loss and social participation. The Sobel method was used to explore the relationship between hearing loss, depression and social participation. RESULTS: Compared with older adults without hearing loss, persons with hearing loss engaged in significantly fewer types of activities (ß = -0.070, 95% CI -0.109, -0.031, P < 0.001) and at a lower frequency (ß = -0.176, 95% CI -0.260, -0.093, P < 0.001). Depression significantly existed in the relationship between hearing loss and social participation as a mediating variable, and the percentage of indirect effects in this relationship were 16.5% and 20.8%. CONCLUSIONS: The findings of this study suggest that when facing an aging society, improving the hearing status of older adults should be considered by policymakers. More efforts should be made to help older adults cope with depression. Geriatr Gerontol Int 2022; 22: 529-535.

Hearing loss, depression, and medical service utilization among older adults: evidence from China.

OBJECTIVES: To acquire a better understanding of the mechanisms underlying the association between hearing loss and medical service utilization, this study examined the relationship between hearing loss, depression, and medical service utilization. STUDY DESIGN: Using the methods of probability proportional to size, a survey conducted in 28 provinces, 150 countries/districts, 450 villages/urban communities, 11,628 households, and 19,816 individuals of China in 2018. METHODS: The data for this article were derived from the 2018 China Health and Retirement Longitudinal Study, which enrolled 14,455 people aged 50-80 years. Hearing loss was determined using self-reported hearing status. Self-reported outpatient visits in the last month and hospitalization within the last year were used to determine medical service utilization. Depression was obtained from the CES-D-10 scale. Logistic regression and stepwise regression methods were used. RESULTS: Older adults with hearing loss problems used significantly more outpatient care services (odds ratio [OR] = 1.292, 95% confidence interval [CI] 1.152, 1.449; P < 0.001) and inpatient care services (OR = 1.238, 95% CI 1.021, 1.501; P < 0.05) than those without hearing loss problems. Following that, individuals with hearing loss problems were more likely to experience depressive symptoms (OR = 1.467, 95% CI 1.345, 1.599; P < 0.001) than those without. Moreover, respondents with depressive symptoms used outpatient care services at a significantly higher rate (OR = 1.292, 95% CI 1.152, 1.449; P < 0.001) and inpatient care service at a significantly higher rate (OR = 1.238, 95% CI 1.021, 1.501; P < 0.05) compared with those without depressive symptom. CONCLUSION: This article discovered that depression acted as a mediation variable in the relationship between hearing loss and medical service utilization. This research provided possible interventions for reducing the burden of the healthcare system and society that older adults with hearing loss imposed.

CC-223 blocks mTORC1/C2 activation and inhibits human hepatocellular carcinoma cells in vitro and in vivo.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related human mortalities. Over-activation of mammalian target of rapamycin (mTOR) is important for HCC tumorigenesis and progression. The current study assessed the potential anti-HCC activity by a novel mTOR kinase inhibitor, CC-223. We demonstrate that CC-223, at nM concentrations, induced profound cytotoxic and anti-proliferative activities against established HCC cell lines (HepG2, KYN-2 and Huh-7) and primary human HCC cells. Meanwhile, CC-223 activated caspase-3/-9 and apoptosis in the above HCC cells. CC-223 concurrently blocked mTORC1 and mTORC2 activation, and its cytotoxicity against HCC cells was much more potent than the traditional mTORC1 inhibitors (RAD001 and rapamycin). Further studies demonstrated that CC-223 disrupted mitochondrial function, and induced mitochondrial permeability transition pore (mPTP) opening and reactive oxygen species (ROS) production. On the other hand, ROS scavengers and mPTP blockers (cyclosporin A or sanglifehrin A) largely attenuated CC-223-induced HepG2 cell apoptosis. In vivo studies showed that oral administration of CC-223 dramatically inhibited growth of HepG2 xenografts in severe combined immuno-deficient (SCID) mice. mTORC1/2 activation was also blocked in xenografts with CC-223 administration. Together, CC-223 simultaneously blocks mTORC1/2 and efficiently inhibits human HCC cells.

Monascus Pigment Rubropunctatin: A Potential Dual Agent for Cancer Chemotherapy and Phototherapy.

The Monascus pigment, rubropunctatin, was extracted and purified from red mold rice (RMR), and its cytotoxic activities against human cervical carcinoma HeLa cells were studied under the conditions with or without light irradiation. The IC50 value of rubropunctatin against HeLa cells in the dark was 93.71 ± 1.96 µM (24 h), while the cytotoxic activity was enhanced more than 3 times (IC50 = 24.02 ± 2.17 µM) under light irradiation (halogen lamp, 500 W; wavelength, 597-622 nm; and fluence rate, 15 mW cm(-2), for 30 min). However, the IC50 value of rubropunctatin against the immortalized human cervical epithelial H8 cells was more than 300 µM, even under light irradiation, indicating that rubropunctatin has a favorable selectivity index (SI). Treatment of HeLa cells with rubropunctatin in the dark or under light irradiation resulted in a dose-dependent apoptosis, as validated by the increase in the percentage of cells in the sub-G1 phase and phosphatidylserine externalization, and the inductive effect on HeLa cell apoptosis was boosted by the light irradiation. In addition, treatment with rubropunctatin alone or under light irradiation was found to induce apoptosis in HeLa cells via the mitochondrial pathway, including loss of mitochondrial membrane potential, activation of caspase-3, caspase-8, and caspase-9, and increase of the level of intracellular reactive oxygen species (ROS). It was suggested that rubropunctatin could be a promising natural dual anticancer agent for photodynamic therapy and chemotherapy.