Protecting mitochondria via inhibiting VDAC1 oligomerization alleviates ferroptosis in acetaminophen-induced acute liver injury.

Acetaminophen (APAP) overdose is a common cause of drug-induced liver injury (DILI). Ferroptosis has been recently implicated in APAP-induced liver injury (AILI). However, the functional role and underlying mechanisms of mitochondria in APAP-induced ferroptosis are unclear. In this study, the voltage-dependent anion channel (VDAC) oligomerization inhibitor VBIT-12 and ferroptosis inhibitors were injected via tail vein in APAP-injured mice. Targeted metabolomics and untargeted lipidomic analyses were utilized to explore underlying mechanisms of APAP-induced mitochondrial dysfunction and subsequent ferroptosis. As a result, APAP overdose led to characteristic changes generally observed in ferroptosis. The use of ferroptosis inhibitor ferrostatin-1 (or UAMC3203) and iron chelator deferoxamine further confirmed that ferroptosis was responsible for AILI. Mitochondrial dysfunction, which is associated with the tricarboxylic acid cycle and fatty acid ß-oxidation suppression, may drive APAP-induced ferroptosis in hepatocytes. APAP overdose induced VDAC1 oligomerization in hepatocytes, and protecting mitochondria via VBIT-12 alleviated APAP-induced ferroptosis. Ceramide and cardiolipin levels were increased via UAMC3203 or VBIT-12 in APAP-induced ferroptosis in hepatocytes. Knockdown of Smpd1 and Taz expression responsible for ceramide and cardiolipin synthesis, respectively, aggravated APAP-induced mitochondrial dysfunction and ferroptosis in hepatocytes, whereas Taz overexpression protected against these processes. By immunohistochemical staining, we found that levels of 4-hydroxynonenal (4-HNE) protein adducts were increased in the liver biopsy samples of patients with DILI compared to that in those of patients with autoimmune liver disease, chronic viral hepatitis B, and non-alcoholic fatty liver disease (NAFLD). In summary, protecting mitochondria via inhibiting VDAC1 oligomerization attenuated hepatocyte ferroptosis by restoring ceramide and cardiolipin content in AILI.

Therapeutic effect of acupuncture combining standard swallowing training for post-stroke dysphagia: A prospective cohort study.

OBJECTIVE: To assess the therapeutic effect of acupuncture combining standard swallowing training for patients with dysphagia after stroke. METHODS: A total of 105 consecutively admitted patients with post-stroke dysphagia in the Affiliated Hospital of Gansu University of Chinese Medicine were included: 50 patients from the Department of Neurology and Rehabilitation received standard swallowing training and acupuncture treatment (acupuncture group); 55 patients from the Department of Neurology received standard swallowing training only (control group). Participants in both groups received 5-day therapy per week for a 4-week period. The primary outcome measures included the scores of Videofluoroscopic Swallow Study (VFSS) and the Standardized Swallowing Assessment (SSA); the secondary outcome measure was the Royal Brisbane Hospital Outcome Measure for Swallowing (RBHOMS), all of which were assessed before and after the 4-week treatment. RESULTS: A total of 98 subjects completed the study (45 in the acupuncture group and 53 in the control group). Significant differences were seen in VFSS, SSA and RBHOMS scores in each group after 4-week treatment as compared with before treatment (P<0.01). Comparison between the groups after 4-week treatment showed that the VFSS P=0.007) and SSA scores (P=0.000) were more significantly improved in the acupuncture group than the control group. However, there was no statistical difference (P=0.710) between the acupuncture and the control groups in RBHOMS scores. CONCLUSIONS: Acupuncture combined with the standard swallowing training was an effective therapy for post-stroke dysphagia, and acupuncture therapy is worth further investigation in the treatment of post-stroke dysphagia.

[Clinical research of chloasma treated with the meridian cosmetology and the impacts on estrogen and progestin].

OBJECTIVE: To observe the efficacy difference between meridian cosmetology and western medicine in the treatment of chloasma and explore the impacts of meridian cosmetology on E2 and PRGE. METHODS: Three hundreds cases of chloasma were randomized into a meridian cosmetology group and a western medication group according to the visit sequence, 150 cases in each one. In the meridian cosmetology group, the meridian regulation, acupuncture based on pattern/syndrome differentiation [at the body acupoints such as Qihai (CV 6), Xuehai (SP 10), Zusanli (ST 36), Sanyinjiao (SP 6), Ganshu (BL 18), Pishu (BL 20) and Shenshu (BL 23), etc.] and the local surrounding needling therapy on the chloasma skin lesion were adopted. In the western medication group, the oral administration of Vitamin C and E was prescribed for 3 months. The clinical efficacy was observed for the patients in the two groups. Additionally, 30 cases were collected from the meridian cosmetology group randomly for the detection of estrogen (E2) and progestin (PRGE) before and after treatment. RESULTS: The effective rate in the meridian cosmetology group was 92.6% (126/136), which was superior to 67.0% (75/112) in the western medication group (P < 0.05). For the patients collected from the meridian cosmetology group, as compared with that before treatment, E2 level was decreased (P < 0.01) and PRGE level was increased (P < 0.05). CONCLUSION: The meridian cosmetology achieves the superior efficacy as compared with the western medication group for the chloasma and it can regulate the levels of E2 and PRGE.