Aripiprazole (ARP) is an atypical anti-psychotic drug widely used to treat schizophrenia and bipolar disorder. The pharmacological effects of ARP on cancer cells are still poorly understood. In this study, anti-cancer effects of ARP on various malignant tumor cells and its molecular mechanism were further carefully examined by using cell proliferation assay, xenograft mouse model, immunoblotting analysis, migration assay, luciferase reporter gene assay, kinase assay, and overexpression strategy. Treatment with ARP induced cytotoxicity in U251 glioma cells, MKN-1 gastric adenosquamous carcinoma cells, and CT26 colon carcinoma cells. ARP suppressed cell proliferation of LN428, MDA-MB-231, and HEK293 cells. Pro-apoptotic factors active caspase-3, -8, and -9, as well as p53, were upregulated, whereas the protein and mRNA levels of anti-apoptotic factor B-cell lymphoma 2 (Bcl-2) decreased. In agreement with the in vitro results, ARP compound also significantly suppressed the growth of tumor masses formed by injecting CT26 colon cancer cells into mice. ARP treatment also effectively decreased the migratory ability of U251 glioma cells by downregulating metalloproteinase-9. Levels of phosphorylated Src, phosphorylated phosphatidylinositide 3-kinase (PI3K), and phosphorylated signal transducer and activator of transcription 3 (STAT3) were significantly decreased following ARP treatment. ARP compound reduced the kinase activity of Src. Our studies suggest that Src may be an important target molecule linked to the antitumor effects of ARP.
Background Lichen sclerosus (LS) is a common autoimmune dermatological condition that is often under-diagnosed in women and has been documented to affect quality of life and sexual function. Aim To determine the prevalence of sexual dysfunction among women with vulvar lichen sclerosus. Methods The authors conducted a systematic review and meta-analysis of the existing research on LS and sexual function in database including PubMed using search terms: lichen sclerosus OR vulvar lichen sclerosus OR vulvar lichen sclerosus et atrophicus OR kraurosis vulvae) AND (sexual function OR sexual functions OR sexual disorder OR sexual disorders OR sexual activity OR sexual activities OR sexual dysfunction OR sexual dysfunctions OR dyspareunia OR vaginismus). Outcomes Nearly 60% of women with lichen sclerosus suffer from sexual dysfunction. Results Two hundred and ten studies were initially identified. Twenty-six articles met inclusion criteria and 3 were excluded as they did not relate to sexual function, were regarding a surgical or medical intervention and sexual dysfunction and one was a review article. Therefore, 23 studies were included in the final analysis resulting in a cumulative 486 participants with LS with 208 patients experiencing any kind of sexual dysfunction. Meta-analysis presented prevalence of sexual dysfunction among LS patients as 59% (95% CI: 48 – 70%). Dyspareunia or generalized pain with intercourse was the most commonly reported type of dysfunction. Clinical Implications Discussing sexual concerns with women with LS could empower them to seek treatment. Strengths and Limitations Few articles met criteria for inclusion. Conclusion A large proportion of women with LS experience sexual dysfunction. More research is needed, especially that which includes biopsy-proven LS and validated tools on sexual function.
Background: Suicide is one of the most important causes of deaths in the United Kingdom, and the numbers are currently increasing. Aim: There are numerous identified determinants of suicidality, and physical multimorbidity is potentially important but is currently understudied. Thus, this study aims to investigate the association of physical multimorbidity with suicidality. Methods: Cross-sectional data from the Adult Psychiatric Morbidity Survey 2007, which was conducted in England between October 2006 and December 2007 by the National Center for Social Research and Leicester University were analyzed. Respondents were asked about 20 physical health conditions, and suicidal ideation and suicide attempts were assessed. Results: Out of 7,403 individuals aged 16 years or over, the prevalence of physical multimorbidity, suicidal ideation, and suicide attempts were 35.1%, 4.3%, and 0.7%, respectively. After adjustment for potential confounders, compared to no physical conditions, 1, 2, 3, and ⩾4 conditions were associated with significant 1.79 (95% CI [1.25, 2.57]), 2.39 (95% CI [1.63, 3.51]), 2.88 (95% CI [1.83, 4.55]), and 6.29 (95% CI [4.12, 9.61]) times higher odds for suicidal ideation. Mediation analysis showed that cognitive problems (mediated percentage 39.2%) and disability (37.5%) explained the largest proportion between multimorbidity and suicidal ideation. Pain (38.0%) and cognitive problems (30.7%) explained the largest proportion between multimorbidity and suicide attempts. Conclusion: In this large sample of UK adults, physical multimorbidity was associated with significantly higher odds for suicidal ideation and suicide attempts. Moreover, several potential mediators were identified, and these may serve as future targets for interventions that aim to prevent suicidality among people with physical multimorbidity.
The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) Delta variant (B.1.617.2) was the predominant variant behind the surges of COVID‐19 in the United States, Europe, and India in the second half of 2021. The information available regarding the defining mutations and their effects on the structure, transmission, and vaccine efficacy of SARS‐CoV‐2 is constantly evolving. With waning vaccine immunity and relaxation of social distancing policies across the globe driving the increased spread of the Delta variant, there is a great need for a resource aggregating the most recent information for clinicians and researchers concerning the Delta variant. Accordingly, this narrative review comprehensively reviews the genetics, structure, epidemiology, clinical course, and vaccine efficacy of the Delta variant. Comparison with the omicron variant is also discussed. The Delta variant is defined by 15 mutations in the Spike protein, most of which increase affinity for the ACE‐2 receptor or enhance immune escape. The Delta variant causes similar symptoms to prototypical COVID‐19, but it is more likely to be severe, with a greater inflammatory phenotype and viral load. The reproduction number is estimated to be approximately twice the prototypical strains present during the early pandemic, and numerous breakthrough infections have been reported. Despite studies demonstrating breakthrough infection and reduced antibody neutralisation, full vaccination effectively reduces the likelihood of severe illness and hospitalisation.
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