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The activation of hepatic stellate cells (HSCs) is a key event during the progression of liver fibrosis (LF). We have previously indicated that NLRP3 inflammasome plays a crucial role in arsenic-induced HSCs activation. However, the mechanism of cascade responses between NLRP3 inflammasome and HSCs activation is unclear. Here, we showed that the transcription and protein level of Hsp47 was upregulated after 4 μM arsenic treatment, both in vivo and in vitro. Additionally, arsenic-induced HSCs activation was remarkably alleviated by the interference of Hsp47. Furthermore, blockage of NLRP3 significantly mitigated the activation of the NLRP3 inflammasome and decreased the expression of Hsp47, thereby attenuating the arsenic-induced HSCs activation. However, the ablation of Hsp47 did not affect the activation of the NLRP3 inflammasome. Notably, the protein-protein interaction between NLRP3 and Hsp47 was observed both in vivo and in vitro , and the target amino acid sequences were further identified. In summary, the present study indicated that NaAsO 2 induced HSCs activation via the NLRP3 inflammasome-Hsp47 pathway. These findings provide direct evidence that Hsp47 may be a potential therapeutic target for arsenic-induced LF. [Display omitted] • Hsp47 plays a critical role in HSCs activation and iAs-induced liver fibrosis. • iAs treatment upregulates Hsp47 via promoting NLRP3 inflammasome activation. • NLRP3 interacts with Hsp47 during the activation of HSCs by iAs. [ABSTRACT FROM AUTHOR]

In this study the State Feelings of Fat Scale (SFF) was translated into Chinese, and its reliability and validity were tested with a sample of 539 Chinese female undergraduates. Participants completed the Chinese version of the SFF Scale, the Eating Disorder Examination Questionnaire, the Social Physique Anxiety Scale, the General Physical Self-Worth Scale, and the attraction body subscale of the Physical Self-Perception Profile. These variables and body mass index were selected as criterion measurements. Two weeks later, 94 participants were recalled to respond to the SFF Scale again. The results of factor analysis supported the unidimensional structure model. Cronbach's alpha coefficient was.87 and the test–retest reliability was.91. The total score for the SFF Scale exhibited a significant correlation with all the criteria. It can be concluded that the Chinese version of the SFF Scale has good reliability and validity and can be used in correlational studies. [ABSTRACT FROM AUTHOR]

Hepatic insulin resistance (IR) is the primary pathology of type 2 diabetes (T2D). The role of the NOD-like receptor protein 3 (NLRP3) inflammasome in arsenic-induced hepatic IR has been previously demonstrated. However, the mechanism of the arsenic-induced activation of the NLRP3 inflammasome is still unclear. Here, we demonstrate that NaAsO 2 downregulated the mRNA and protein level of Annexin A1 (AnxA1), an anti-inflammatory factor, in rat livers and L-02 cells. Moreover, AnxA1 overexpression significantly alleviated arsenic-induced NLRP3 inflammasome activation and IR in L-02 cells. Importantly, Co-immunoprecipitation (Co-IP) results showed that AnxA1 1–190 peptide could bind to the domain encompassing amino acids 1–210 and 211–550 of NLRP3. In conclusion, our experiments demonstrated that arsenic exposure could activate the NLRP3 inflammasome and IR by inhibiting the AnxA1 activity. These findings suggest that AnxA1 may be a promising therapeutic target of arsenicosis. [Display omitted] • NaAsO 2 decreased the expression of AnxA1 in hepatocytes. • NaAsO 2 -activated NLRP3 inflammasome was inhibited by AnxA1 overexpression. • AnxA1 target-binding of NLRP3 specially inhibited the expression of NLRP3. [ABSTRACT FROM AUTHOR]

This study aimed to examine the impact of childhood maltreatment on callous-unemotional (CU) traits among incarcerated male adolescents, focusing primarily on the roles of parental attachment and emotional intelligence. A total of 454 male incarcerated adolescents from two juvenile correctional facilities, ranging in age from 14 to 18 years, completed a set of questionnaires consisting of a childhood trauma questionnaire, parent-attachment scale, emotional intelligence scale, and the Inventory of CU traits. The results revealed that childhood maltreatment, parental attachment, and emotional intelligence were all correlated with CU traits. Structural equation modeling analysis and the bootstrap test indicated that parental attachment and emotional intelligence mediated, in part, the effect of childhood maltreatment on CU traits. These findings expand the outcomes of previous research and shed light on how childhood maltreatment is related to CU traits. [ABSTRACT FROM AUTHOR]

As an environmental toxicant, arsenic exposure may cause insulin resistance (IR). Previous studies have shown that pyroptosis plays an important role in the occurrence and development of IR. Although gasdermin D (GSDMD) functions as an executor of pyroptosis, the relationship between GSDMD-mediated pyroptosis and hepatic IR remains unclear. Here, we observed that sodium arsenite (NaAsO 2) activated NOD-like receptors containing pyrin domain 3 (NLRP3) inflammasomes, promoted GSDMD activation, induced pyroptosis and hepatic IR, while GSDMD knockdown attenuated pyroptosis and hepatic IR caused by NaAsO 2. However, GSDMD interference did not affect NLRP3 activation. Ubiquitination modification is widely involved in protein regulation and intracellular signal transduction, and whether it regulates GSDMD and affects its degradation, and exerts effects on arsenic-induced pyroptosis remain unclear. We observed that NaAsO 2 reduced the K48- and K63-linked ubiquitination of GSDMD, thereby inhibiting its degradation through the ubiquitin-proteasome system (UPS) and the autophagy-lysosome pathway (ALP), causing GSDMD to accumulate and lyse into GSDMD-N, which promoted pyroptosis. In summary, we demonstrated that GSDMD participated in arsenic-induced hepatic IR. Moreover, NaAsO 2 reduced GSDMD ubiquitination and decreased its intracellular degradation, aggravating pyroptosis and hepatic IR. We have revealed the molecular mechanism underpinning arsenic-induced IR, and we provide potential solutions for the prevention and treatment of type 2 diabetes (T2D). [Display omitted] • The reduction of GSDMD would attenuate the arsenic-induced pyroptosis and insulin resistance. • Exposure to NaAsO 2 would reduce the ubiquitination level of GSDMD. • Ubiquitinated GSDMD would be degraded by ubiquitin-proteasome system and autophagy-lysosome pathway. [ABSTRACT FROM AUTHOR]