Asmussenlam4779
In line with the results, we then observed that the anti-arthritic effect of SIN was significantly attenuated in Nrf2 deficient (Nrf2-/-) mice. Notably, we found that p62 expression and phosphorylation at Thr269/Ser272 remarkably reduced, while p62 phosphorylation at Ser351 was up-regulated in Nrf2 deficient mice compared to its wild littermates, indicating that Nrf2 probably negative regulates p62 phosphorylation at Ser351. APG-2449 Collectively, our findings demonstrate that SIN phosphorylated p62 at Ser351 (corresponding to human Ser349) to degrade Keap1 expression and accumulate Nrf2 expression, increased p62 expression and phosphorylation at Thr269/Ser272 to activate p62-Keap1-Nrf2 axis, and finally exerted anti-arthritic effect. The current study not only clarified the anti-arthritic characteristics of SIN but also provided the clue to elucidate the correlation of p62 phosphorylation sites and Nrf2 signaling activation.The factors behind the pathogenesis of lung cancer are not clear, and treatment failure is generally caused by drug resistance, recurrence, and metastasis. Development of new therapeutic agents to overcome drug-resistance remains a challenge clinically. Various extracts of Foeniculum vulgare have shown promising anticancer activity; however, effects on lung cancer and the underlying molecular mechanisms of action are not clear. In the present study, we found that the ethanol extract of Foeniculum vulgare seeds (EEFS) significantly reduced lung cancer cell growth in vitro and in vivo. EEFS decreased the viability of and triggered apoptosis in the lung cancer cell lines NCI-H446 and NCI-H661. EEFS induced apoptosis mainly through inhibition of Bcl-2 protein expression, reduction of mitochondrial membrane potential, and release of Cytochrome C. Moreover, EEFS significantly inhibited colony formation and cell migration in lung cancer cells. EEFS also effectively inhibited the growth of xenograft tumors derived from NCI-446 cells by reducing Bcl-2 protein expression and inducing apoptosis. Taken together, these findings suggest that EEFS exerts anti-lung cancer activity by targeting the Bcl-2 protein and may have potential as a therapeutic drug for lung cancer.
Hongjingtian injection (HJT) has been widely used in the clinic to treat coronary heart disease in China. However, the underlying mechanisms of therapies still need to be illustrated. The present study aims to determine whether HJT protects against myocardial ischemia reperfusion injury via Reactive Oxygen Species (ROS)-induced autophagic flux and apoptosis and, if so, to explore the underlying mechanisms.
In vivo myocardial protection and autophagy regulation of HJT in myocardial ischemia reperfusion injury in C57BL/6 J and CAG-RFP-EGFP-LC3 transgenic C57BL/6 J mice were investigated. In vitro, the effects of HJT on apoptosis, autophagic flux, oxidative stress and mitochondrial function were observed in H
O
-induced H9c2 cells. In addition, apoptosis-related proteins and autophagy-related proteins were assessed to explore the underlying mechanisms.
HJT significantly decreased the infarct area and cell apoptosis after myocardial ischemia reperfusion injury in C57BL/6 J mice. Autophagic flux was reduced by HJT treatment after myocardial ischemia reperfusion injury in CAG-RFP-EGFP-LC3 transgenic C57BL/6 J mice. HJT inhibited H
O
-induced cell apoptosis by significantly decreasing the levels of cleaved caspase 3 and increasing the Bcl-2/Bax ratio. HJT inhibited autophagic flux after H
O
stimulation by significantly decreasing LC3-Ⅱ and p-AMPK expression and increasing p-mTOR. HJT inhibited ROS production and improved mitochondrial function in H
O
-induced cells by significantly increasing the mitochondrial membrane potential, intracellular ATP contents and oxygen consumption.
The beneficial effects of HJT in treating myocardial ischemia reperfusion are partially due to improved mitochondrial function and regulated autophagy to inhibit cell apoptosis through the AMPK/mTOR pathway.
The beneficial effects of HJT in treating myocardial ischemia reperfusion are partially due to improved mitochondrial function and regulated autophagy to inhibit cell apoptosis through the AMPK/mTOR pathway.Previous research has linked certain psychological disorders, including obsessive-compulsive disorder (OCD), to the experience of disgust and how it is interpreted/appraised. Therefore, the present study examined whether targeting primary and secondary disgust appraisals (i.e., cognitive reappraisal) in individuals with moderate to high OCD-relevant contamination fears can effectively reduce disgust. Fifty-two participants were randomly assigned to one of three conditions; two of which involved reading a brief script modifying either a primary disgust appraisal (i.e., likelihood of a feared outcome) or a secondary disgust appraisal (i.e., the individual's ability to cope), and a third control condition with no reappraisal script. Following this experimental manipulation of disgust appraisal, participants completed two contamination-relevant behavioural approach tasks which involved 1) increasing proximity to, and eventually touching, a dead cockroach, and 2) drinking apple juice from an unused urine sample collection container. Results indicated that the interventions successfully modified their intended appraisal targets. Furthermore, on the second behavioural approach task, the secondary reappraisal condition demonstrated significantly less disgust-related avoidance relative to the control condition and reported significantly less disgust relative to the primary reappraisal condition. Our results incrementally add to the existing literature that emphasises the potential advantages of modifying disgust appraisals and specifically secondary disgust appraisals when treating disgust-based psychological disorders.
Anxiety disorders are among the most common mental health conditions. Individuals with anxiety typically seek services in primary, rather than specialty, care. While there is significant evidence supporting the efficacy and effectiveness of cognitive behavioral therapy (CBT) for anxiety disorders, there have been no naturalistic studies reporting anxiety-specific treatment outcomes in primary care.
Participants (N = 1,589) were recruited from a multi-state, multi-site primary care practice, with 491 participants endorsing moderate to severe anxiety at baseline and engaging in at least one CBT session. Data was drawn from a psychotherapy tracking database.
Among participants with moderate to severe anxiety who engaged in CBT, a significant decrease in anxiety and depression symptoms was observed over the course of psychotherapy (p< .001, d = 0.57-0.95). Rates of reliable change, response, and remission varied across diagnostic categories. The use of CBT interventions also varied across diagnoses in line with evidence-based treatment recommendations.
