Scutellarin regulates microglia-mediated TNC1 astrocytic reaction and astrogliosis in cerebral ischemia in the adult rats

Additional file 1: (A). Scutellarin at 0.54 mM did not elicit a noticeable reaction of GFAP/iNOS in TNC1. (B). iNOS mRNA expression in TNC1 astrocytes remained relatively unchanged at all time-points following treatment with BM, BM + L and CM; however, when incubated with CM + L for various time points, TNC1 showed a remarkable increase in iNOS peaking at 24 h. (C). Confocal images showing iNOS (C1-3) expression in TNC1 astrocytes incubated with different medium for 24 h. Compared with cells incubated in BM (C1) and BM + L (C2), TNC1 astrocytes incubated with CM + L (C3) were hypertrophic and showed a marked increase in iNOS immunofluorescence. Scale bars: 20 μm. DAPI—blue

Optimizing glycerosome formulations via an orthogonal experimental design to enhance transdermal triptolide delivery

Triptolide exerts strong anti-inflammatory and immunomodulatory effects; however, its oral administration might be associated with side effects. Transdermal administration can improve the safety of triptolide. In this study, glycerosomes were prepared as the transdermal vehicle to enhance the transdermal delivery of triptolide. With entrapment efficiency and drug loading as dependent variables, the glycerosome formulation was optimized using an orthogonal experimental design. Phospholipid-to-cholesterol and phospholipid-to-triptolide mass ratios of 30:1 and 5:1, respectively and a glycerol concentration of 20 % (v/v) were used in the optimization. The glycerosomes prepared with the optimized formulation showed good stability, with an average particle size of 153.10 ± 2.69 nm, a zeta potential of –45.73 ± 0.60 mV and an entrapment greater than 75 %. Glycerosomes significantly increased the transdermal delivery of triptolide compared to conventional liposomes. As efficient carriers for the transdermal delivery of drugs, glycerosomes can potentially be used as an alternative to oral triptolide administration

Current situation and related factors of occupational stress of employees of a petrochemical enterprise

BackgroundOccupational stress has become one of the main factors affecting people's physical and mental health, and there are many sources of occupational stress in petrochemical enterprises. ObjectiveTo evaluate the current situation of occupational stress and its related factors among employees in a petrochemical enterprise, and to provide a scientific basis for reduing the risk of occupational stress among employees in petrochemical enterprises. MethodsIn June 2022, a cross-sectional questionnaire survey was conducted in a petrochemical enterprise in Hainan, including a general information questionnaire for basic information, the Effort-Reward Imbalance (ERI) for occupational stress, and the Pittsburgh Sleep Quality Index (PSQI) for sleep quality. Chi-square test was used to compare differences in positive occupational stress by demographic characteristics, occupational characteristics, behavior, and occupational disease hazards. Logistic regression was employed to evaluate factors associated with occupational stress. ResultsOf the 1129 questionnaire distributed, a total of 999 valid questionnaire were returned,with a valid recovery rate of 88.5%. The positive rate of occupational stress among employees in the petrochemical enterprise was 29.5%. There were statistically significant differences in the positive rate of occupational stress among the employees grouped by gender, age, marital status, body mass index (BMI), monthly income, length of service, smoking, weekly working hours, type of work, working mode, sleep quality, noise exposure, and high temperature exposure (P<0.05). In terms of positive occupational stress among subcategories: workers being male (vs. female), working ＞40 h per week (vs. ≤40 h per week), regular day shift (vs. shift work), smoking (vs. not smoking), with exposure to noise and heat (vs. without such exposure), and having poor sleep quality (vs. good sleep quality) reported higher positive occupational stress rates (P＜0.05). The results of pairwise comparison showed that the positive rate of occupational stress in divorced (50.0%) or married (32.0%) workers was higher than that in single (27.1%) workers, and higher in operation workers (30.6%) than in other types of work (20.5%) (P＜0.05). The trend chi-square results showed that the positive rate of occupational stress increased linearly with the increase of age, length of service, BMI, or monthly income (P＜0.05). The results of logistic regression analysis after adjustment showed that workers who worked ＞40 h a week had a higher risk of occupational stress than those who worked ≤40 h a week, and the OR (95%CI) was 1.909 (1.135, 3.211); the workers of other types of work had a lower risk of reporting occupational stress than operation workers, and the OR (95%CI) was 0.513 (0.272, 0.968); the workers with noise exposure had a higher risk of occupational stress than the workers without, and the OR (95%CI) was 2.457 (1.070, 5.642). ConclusionThe positive rate of occupational stress among employees in this petrochemical enterprise is high. Among them, operators, working hours per week＞40 h, and noise exposure may increase the incidence of occupational stress. The enterprise should actively take measures to reduce the occurrence of occupational stress among employees

Mechanism, structural and functional insights into nidovirus-induced double-membrane vesicles

During infection, positive-stranded RNA causes a rearrangement of the host cell membrane, resulting in specialized membrane structure formation aiding viral genome replication. Double-membrane vesicles (DMVs), typical structures produced by virus-induced membrane rearrangements, are platforms for viral replication. Nidoviruses, one of the most complex positive-strand RNA viruses, have the ability to infect not only mammals and a few birds but also invertebrates. Nidoviruses possess a distinctive replication mechanism, wherein their nonstructural proteins (nsps) play a crucial role in DMV biogenesis. With the participation of host factors related to autophagy and lipid synthesis pathways, several viral nsps hijack the membrane rearrangement process of host endoplasmic reticulum (ER), Golgi apparatus, and other organelles to induce DMV formation. An understanding of the mechanisms of DMV formation and its structure and function in the infectious cycle of nidovirus may be essential for the development of new and effective antiviral strategies in the future

Antagonist Effect of Triptolide on AKT Activation by Truncated Retinoid X Receptor-alpha

Background: Retinoid X receptor-alpha (RXR alpha) is a key member of the nuclear receptor superfamily. We recently demonstrated that proteolytic cleavage of RXR alpha resulted in production of a truncated product, tRXR alpha, which promotes cancer cell survival by activating phosphatidylinositol-3-OH kinase (PI3K)/AKT pathway. However, how the tRXR alpha-mediated signaling pathway in cancer cells is regulated remains elusive. Methodology/Principal Findings: We screened a natural product library for tRXR alpha targeting leads and identified that triptolide, an active component isolated from traditional Chinese herb Trypterygium wilfordii Hook F, could modulate tRXR alpha-mediated cancer cell survival pathway in vitro and in animals. Our results reveal that triptolide strongly induces cancer cell apoptosis dependent on intracellular tRXR alpha expression levels, demonstrating that tRXR alpha serves as an important intracellular target of triptolide. We show that triptolide selectively induces tRXR alpha degradation and inhibits tRXR alpha-dependent AKT activity without affecting the full-length RXR alpha. Interestingly, such effects of triptolide are due to its activation of p38. Although triptolide also activates Erk1/2 and MAPK pathways, the effects of triptolide on tRXR alpha degradation and AKT activity are only reversed by p38 siRNA and p38 inhibitor. In addition, the p38 inhibitor potently inhibits tRXR alpha interaction with p85 alpha leading to AKT inactivation. Our results demonstrate an interesting novel signaling interplay between p38 and AKT through tRXR alpha mediation. We finally show that targeting tRXR alpha by triptolide strongly activates TNF alpha death signaling and enhances the anticancer activity of other chemotherapies Conclusions/Significance: Our results identify triptolide as a new xenobiotic regulator of the tRXR alpha-dependent survival pathway and provide new insight into the mechanism by which triptolide acts to induce apoptosis of cancer cells. Triptolide represents one of the most promising therapeutic leads of natural products of traditional Chinese medicine with unfortunate side-effects. Our findings will offer new strategies to develop improved triptolide analogs for cancer therapy.National Natural Science Foundation of China [NSFC: 30971445, 90913015, 91129302]; NSFC/Hong Kong Research Grants Council [NSFC/RGC: 30931160431/N_HKU 735/09]; Natural Science Foundation of Fujian Province [2009J01198

National identity predicts public health support during a global pandemic

Changing collective behaviour and supporting non-pharmaceutical interventions is an important component in mitigating virus transmission during a pandemic. In a large international collaboration (Study 1, N = 49,968 across 67 countries), we investigated self-reported factors associated with public health behaviours (e.g., spatial distancing and stricter hygiene) and endorsed public policy interventions (e.g., closing bars and restaurants) during the early stage of the COVID-19 pandemic (April-May 2020). Respondents who reported identifying more strongly with their nation consistently reported greater engagement in public health behaviours and support for public health policies. Results were similar for representative and non-representative national samples. Study 2 (N = 42 countries) conceptually replicated the central finding using aggregate indices of national identity (obtained using the World Values Survey) and a measure of actual behaviour change during the pandemic (obtained from Google mobility reports). Higher levels of national identification prior to the pandemic predicted lower mobility during the early stage of the pandemic (r = −0.40). We discuss the potential implications of links between national identity, leadership, and public health for managing COVID-19 and future pandemics.publishedVersio