The small molecule chemical compound cinobufotalin attenuates resistance to DDP by inducing ENKUR expression to suppress MYH9-mediated c-Myc deubiquitination in lung adenocarcinoma.

The small molecule chemical compound cinobufotalin (CB) is reported to be a potential antitumour drug that increases cisplatin (DDP) sensitivity in nasopharyngeal carcinoma. In this study, we first found that CB decreased DDP resistance, migration and invasion in lung adenocarcinoma (LUAD). Mechanistic studies showed that CB induced ENKUR expression by suppressing PI3K/AKT signalling to downregulate c-Jun, a negative transcription factor of ENKUR. Furthermore, ENKUR was shown to function as a tumour suppressor by binding to ß-catenin to decrease c-Jun expression, thus suppressing MYH9 transcription. Interestingly, MYH9 is a binding protein of ENKUR. The Enkurin domain of ENKUR binds to MYH9, and the Myosin_tail of MYH9 binds to ENKUR. Downregulation of MYH9 reduced the recruitment of the deubiquitinase USP7, leading to increased c-Myc ubiquitination and degradation, decreased c-Myc nuclear translocation, and inactivation of epithelial-mesenchymal transition (EMT) signalling, thus attenuating DDP resistance. Our data demonstrated that CB is a promising antitumour drug and may be a candidate chemotherapeutic drug for LUAD patients.

Dysbiosis of gut microbiota and decreased propionic acid associated with metabolic abnormality in Cushing's syndrome.

Objective: Chronic hypercortisolism leads to a phenotype resembling metabolic syndrome. We aimed to investigate the association between gut microbiota and metabolic abnormalities in endogenous hypercortisolism (Cushing's syndrome). Methods: A total of 23 patients with Cushing's syndrome (18 female and 5 men, aged 47.24 ± 12.99 years) and 30 age-, sex-and BMI-matched healthy controls (18 female and 12 men, aged 45.03 ± 6.69 years) were consecutively recruited. Differences in gut microbiota and plasma short-chain fatty acid (SCFAs) concentrations between the Cushing's syndrome patients and controls were analyzed by 16S rRNA sequencing and gas chromatography-mass spectrometry (GC-MS). Results: Compared to the controls, the Simpson and Pielou indices of α diversity were dramatically decreased in Cushing's syndrome (P < 0.05). The gut microbiota community structure differed significantly between Cushing's syndrome patients and controls. Compared to controls, the bacterial communities of the Cushing's syndrome patients were enriched in Proteobacteria and Escherichia-Shigella, and depleted in Firmicutes, including Agathobacter, Blautia, Anaerostipes, Eubacterium_eligens_group, and Lachnospira. Spearman analysis demonstrated that HbA1c, SBP, DBP, and cortisol levels were significantly positively correlated with Proteobacteria and Escherichia-Shigella, whereas negatively correlated with Agathobacter, Blautia, Anaerostipes, Eubacterium_hallii_group, and Lachnospira, etc. Cushing's syndrome patients also had a lower propionic acid concentration (0.151±0.054 vs. 0.205±0.032 µg/mL, P=0.039) than controls. Furthermore, the level of propionic acid was negatively correlated with systolic pressure and cortisol levels (P<0.05). Conclusion: Gut microbiota dysbiosis and decreased propionic acid levels were observed in patients with Cushing's, suggesting that the gut microbiota may be a potential therapeutic intervention target to improve hypercortisolism-related metabolic abnormalities.

[Therapeutic effects of "kidney three-needle" therapy plus fire needling therapy in treatment of post-stroke urinary incontinence].

OBJECTIVE: To observe the efficacy of "kidney three-needle" therapy［Qugu（CV2） and 1 cun to the left and right of CV2］ and the pricking technique of fire needing therapy on urinary frequency and maximal bladder volume in potients with post-stroke urinary incontinence. METHODS: A total of 60 patients with post-stroke urinary incontinence were collected according to the inclusion and exclusion criteria and were randomized into an observation group (30 cases) and a control group (30 cases). On the base of the routine medication and rehabilitation treatment, acupuncture was applied to the general acupoints for motor impairment and speech disorder in the two groups. Additionally, the combination of "kidney three-needle" therapy and the pricking technique of fire needling therapy was used for urinary incontinence in the observation group and the common acupuncture was applied in the control group. Needles were retained for 30 min and acupuncture was provided once daily, 5 days a weeks, 2 weeks of treatment as one course. Both groups were treated for 3 courses. Before and after treatment, the rank of daytime urinary frequency was compared in the patients of the two groups. Ultrasound B was adopted to determine the maximal bladder volume. The total effective rate was compared between the two groups. RESULTS: After treatment, the rank of daytime urinary frequency all reduced significantly as compared with that before treatment in the patients of the two groups (P<0.01)， and the observation group was lower than the control group (P<0.05). After the treatment, the maximal bladder volume increased significantly as compared with that before treatment in the self-comparison of each group (P<0.01) and the volume in the observation group was significantly higher than that in the control group (P<0.01). The total effective rate was 93.3% (28/30) in the observation group and was 66.7% (20/30) in the control group. The total effective rate in the observation group was higher obviously than that in the control group (P<0.05). CONCLUSION: The combination of "kidney three-needle" therapy and the pricking technique of fire needling therapy significantly reduces the rank of daytime urinary frequency and increases maximal bladder volume in the patients with post-stroke urinary incontinence. The therapeutic effect of such combined acupuncture treatment is better than the common acupuncture therapy.