Edmondsonavila3828

Imbalance of redox homeostasis may be responsible for the resistance of cancer to chemotherapy. Currently, increasing studies demonstrated that vitamin K3 (VK3), which promoted the production of ROS, had potential to be developed as an anti-tumor agent. We found SKOV3/DDP cells with high levels of p62 were insensitive to VK3 compared with SKOV3 cells. Furthermore, Nrf2 downstream antioxidant genes such as HO-1(heme oxygenase 1) and NQO1 (NAD (P) H quinone oxidoreductase 1) were upregulated in SKOV3/DDP cells with VK3 treatment, which indicated VK3 activated Nrf2 signaling in SKOV3/DDP cells. Moreover, co-localization of p62 and Keap1 was also observed. Suppression of p62 expression increased the apoptosis induced by VK3, and the expression of Nrf2, HO-1 and NQO1 were all downregulated in SKOV3/DDP cells. Our results suggested that overexpressed p62 may protect cells from oxidative damage caused by VK3 through activating Keap1/Nrf2 signaling in ovarian cancer. © The author(s).The identification of driver mutations in epidermal growth factor receptor, anaplastic lymphoma kinase, the BRAF and ROS1 genes and subsequent successful clinical development of kinase inhibitors not only significantly improves clinical outcomes but also facilitates the discovery of other novel driver mutations in non-small cell lung cancer. These driver mutations can be categorized into mutations in or near the kinase domain, gene amplification or fusion. In this review, BRAF V600E, EGFR and HER-2 exon 20 mutation, FGFR1-4, K-RAS, MET, neuregulin-1, NRTK, PI3K/AKT/mTOR, RET and ROS1 gene aberration and their therapeutics will be discussed. © The Author(s), 2020.Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder with a multifactorial pathophysiology. The gut microbiota differs between patients with IBS and healthy individuals. After a bout of acute gastroenteritis, postinfection IBS may result in up to approximately 10% of those affected. Small intestinal bacterial overgrowth (SIBO) is more common in patients with IBS than in healthy individuals, and eradication of SIBO with systemic antibiotics has decreased symptoms of IBS in some patients with IBS and SIBO. The nonsystemic (i.e. low oral bioavailability) antibiotic rifaximin is indicated in the United States and Canada for the treatment of adults with IBS with diarrhea (IBS-D). The efficacy and safety of 2-week single and repeat courses of rifaximin have been demonstrated in randomized, placebo-controlled studies of adults with IBS. Rifaximin is widely thought to exert its beneficial clinical effects in IBS-D through manipulation of the gut microbiota. However, current studies indicate that rifaximin induces only modest effects on the gut microbiota of patients with IBS-D, suggesting that the efficacy of rifaximin may involve other mechanisms. Indeed, preclinical data reveal a potential role for rifaximin in the modulation of inflammatory cytokines and intestinal permeability, but these two findings have not yet been examined in the context of clinical studies. The mechanism of action of rifaximin in IBS is likely multifactorial, and further study is needed. © The Author(s), 2020.Background Inflammatory bowel disease (IBD) needs early interventions and an individual specialist-patient relationship. Distance from a tertiary IBD center might affect patient's disease course and outcome. We investigated whether the patient-to-specialist distance has an impact on the disease course using the well-defined patient collective of the Swiss Inflammatory Bowel Disease Cohort Study (SIBDCS). Methods Patient's home address at diagnosis (postal zip code) was extracted from the SIBDCS database. Distance between each zip code and the nearest located IBD specialist center was calculated and classified into the following three sections based on proximity 35 km (group 3). Results Our study included in total 408 IBD patients [234 Crohn's disease (CD), 154 ulcerative colitis (UC), 20 IBD unclassified (IBDU)]. Median age was lowest in group 2 at diagnosis (G1 28 years; G2 21 years, G3 26 years, p  less then  0.01). The diagnostic delay did not differ between groups. CD patients in group 1 were treated more often with anti-tumor necrosis factor (TNF) agents (72% versus 56%, p = 0.04) and 5-aminosalicylates (44% versus 28%, p = 0.04) than in group 3. UC/IBDU patients in group 1 were treated more often with corticosteroids than patients in group 3 (83% versus 58%, p  less then  0.01). The occurrence of IBD-related surgeries did not differ between groups. Conclusions Patient-to-specialist distance might affect drug treatment. However, disease course and the need for IBD-related surgery does not seem to be associated with a longer distance to specialist care in Switzerland. © The Author(s), 2020.Background Stigma towards people diagnosed with a severe mental disorder (SMD) is one of the main obstacles for these service users to receive timely and relevant healthcare. This study was undertaken to understand how stigmatizing attitudes are demonstrated towards people with SMD in primary healthcare centers (PHC) from the perspective of those affected and primary healthcare professionals. check details Methods We used a qualitative exploratory research design to contrast the differences and similarities regarding stigmatizing attitudes towards people with SMD in primary healthcare centers (PHC) from the perspective of two groups (i) people diagnosed with a severe mental disorder, and (ii) healthcare professionals. Data was collected through semi-structured interviews and discussion groups and subsequently analyzed using Atlas.ti software. Results Our results indicate that both service users and healthcare professionals manifest stereotypes, prejudices, and discriminatory behavior in health care. In addition, structural aspects of the health system and organizational culture appear to contribute to stigmatization. Both groups agreed that there is a need for healthcare professionals to have more education, specialization, and skill development related to mental health issues. Conclusions Interventions to reduce the stigma towards people with SMD in PHC must consider delivery of information about mental disorders, development of skills in the healthcare professionals, and modifications in the culture of the health centers. © The Author(s) 2020.