Development of chemoresistance remains a major challenge in treating esophageal squamous cell carcinoma (ESCC) patients despite treatment advances. However, the role of RAC1 in chemoresistance of ESCC and the underlying mechanisms remain largely unknown. In this study, we found that higher levels of RAC1 expression were associated with poorer prognosis in ESCC patients. Enhanced RAC1 expression increased cell proliferation, migration, and chemoresistance in vitro . Combination therapy using RAC1 inhibitor EHop‐016 and cisplatin significantly promoted cell viability inhibition, G2/M phase cycle arrest, and apoptosis when compared to each monotherapy. Mechanistically, glycolysis was significantly downregulated in the RAC1 inhibitor monotherapy group and the combination group via inhibiting AKT/FOXO3a signaling when compared to the control group. Moreover, the silencing of RAC1 inhibited AKT/FOXO3a signaling and cell glycolysis while the upregulation of RAC1 produced an opposite effect. In murine xenograft models, the tumor volume and the expression of glycolytic enzymes were significantly reduced in combination therapy when compared to each monotherapy group. Overall, our study demonstrates that targeting RAC1 with an inhibitor overcomes cisplatin resistance in ESCC by suppressing glycolytic enzymes, which provides a promising strategy for treatment of ESCC in clinical practice.

Background Seeking online health information (OHI) has become a common practice globally. The information seekers could face health risks if they are not proficient in OHI literacy. The OHI-seeking behaviors and skills of Chinese college students, the largest proportion of college students in the world, are understudied. This study was aimed to describe OHI-seeking behaviors and skills of college students in Guangdong, China. Methods College students in the Guangdong province with OHI-seeking experience were invited via WeChat, QQ, and Sina Weibo using QR code posters and flyers for participation in this online anonymized questionnaire-based study. Data on demographics, OHI literacy, information resources, search approaches, and behaviors were collected. The relationship between perceived OHI literacy and high-risk behaviors was investigated by bivariate logistic regression analysis. Results Respondents were 1203 college students with a mean age of 20.6 years, females (60.2%), and undergraduates (97.2%). They sought health information via websites (20.3%), WeChat (2.6%), or both (77.1%). Baidu was the main search engine, and baike.baidu.com (80.3%), Zhihu.com (48.4%), and Zhidao.baidu.com (35.8%) were top three among 20 searched websites for information about self-care (80.7%), general health (79.5%), disease prevention (77.7%), self-medication (61.2%), family treatment (40.9%), drugs (37.7%), western medications (26.6%), hospitals (22.7%), physicians (21.4%), and Traditional Chinese Medicine (15.6%). Despite most respondents (78%) lacked confidence in the evidence quality and satisfaction with the results, only 32.4% further consulted doctors. Many (> 50%) would recommend the retrieved information to others. About 20% experienced hacking/Internet fraud. Cronbach’s alpha for the internal consistency of OHI literacy was 0.786. Bivariate logistic regression analysis showed that students who believed they can judge the evidence level of OHI were more likely to self-diagnose (OR = 2.2, 95%CI, 1.6–3.1) and look for drug usage (OR = 3.1, 95%CI, 1.9–5.0). Conclusions This study reveals Chinese college students’ heavy reliance on OHI to manage their own and others’ health without sufficient knowledge/skills to identify misinformation and disinformation. The apparent risky information-seeking behaviors of Chinese college students warrant the provision of regulated, accurate, and actionable health information; assurance of cybersecurity; and health information literacy promotion in colleges by concerned authorities.

Background Exosomes secreted by peritoneal macrophages (pMφ) are deeply involved in the development of endometriosis (EMs). Exosomes can mediate cell-to-cell communication by transferring biological molecules. This study aimed to explore the effect and mechanism of exosomal long non-coding RNA (lncRNA) CHL1-AS1 derived from pMφ on EMs. Materials and Methods Exosomes (exo) from pMφ were isolated, identified, and co-cultured with ectopic endometrial stromal cells (eESCs) to investigate the biological functions of pMφ-exo. qRT-PCR was used to detect the expression of lncRNA CHL1-AS1 in pMφ-exo from EMs and control patients and verify the transportation of lncRNA CHL1-AS1 from pMφ to eESCs. The effects of exosomal lncRNA CHL1-AS1 on eESC proliferation, migration, invasion, and apoptosis were also detected. The relationships among lncRNA CHL1-AS1, miR-610, and MDM2 (mouse double minute 2) were verified by dual-luciferase reporter assay. The in vivo experiments were conducted to verify the effects of exosomal lncRNA on EMs using a xenograft model of EMs. Results Exosomes from pMφ were successfully isolated. EMs-pMφ-exo promoted eESC proliferation, migration, and invasion and inhibited their apoptosis. lncRNA CHL1-AS1 was upregulated in EMs-pMφ-exo and transported from pMφ to eESCs via exosomes. lncRNA CHL1-AS1 was found to act as a competing endogenous RNA of miR‑610 to promote the expression of MDM2. EMs-pMφ-exo shuttled lncRNA CHL1-AS1 to promote eESC proliferation, migration, and invasion and inhibit apoptosis by downregulating miR-610 and upregulating MDM2. Furthermore, exosomal lncRNA CHL1-AS1 promoted EMs lesions growth by increasing MDM2 in vivo. Conclusion The results demonstrate that exosomal lncRNA CHL1-AS1 promotes the proliferation, migration, and invasion of eESCs and inhibits their apoptosis by downregulating miR-610 and upregulating MDM2, which might be a potential therapeutic target for EMs.

Accumulating evidence has suggested a role of the small GTPase Ras homolog gene family member A (RhoA) in DNA damage response (DDR) in addition to its traditional function of regulating cell morphology. In DDR, 2 key components of DNA repair, ataxia telangiectasia-mutated (ATM) and flap structure-specific endonuclease 1 (FEN1), along with intracellular reactive oxygen species (ROS) have been shown to regulate RhoA activation. In addition, Rho-specific guanine exchange factors (GEFs), neuroepithelial transforming gene 1 (Net1) and epithelial cell transforming sequence 2 (Ect2), have specific functions in DDR, and they also participate in Ras-related C3 botulinum toxin substrate 1 (Rac1)/RhoA interaction, a process which is largely unappreciated yet possibly of significance in DDR. Downstream of RhoA, current evidence has highlighted its role in mediating cell cycle arrest, which is an important step in DNA repair. Unraveling the mechanism by which RhoA modulates DDR may provide more insight into DDR itself and may aid in the future development of cancer therapies.

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