E2F1-driven histone demethylase KDM6B enhances thyroid malignancy via manipulating TFEB-dependent autophagy axis.

Aberrant epigenetic modifications or events regulate autophagy to influence tumor progression, which has gained increasing attention. KDM6B is an essential histone demethylase that participates in multiple processes of tumors, but its role in thyroid carcinoma (THCA) remains to be unknown. Here, in this study, we used the MTT assay to screen and validate that KDM6B is an essential demethylase for THCA. KDM6B promotes THCA proliferation, migration, invasion in vitro and in vivo. Transcriptional factor E2F1 directly binds to the promoter region of KDM6B and regulates its mRNA levels in THCA. E2F1 partially depended on KDM6B to exert its oncogenic functions. Mechanistically, KDM6B binds to TFEB promoter region and mediates the demethylation of H3K27me3. KDM6B depended on TFEB to activate a series of lysosomal-related genes. KDM6B enhances autophagy process, as evidenced by elevated p62 and Beclin-1 proteins. KDM6B depended on TFEB-driven autophagy activity to accelerate THCA progression. Lastly, targeting autophagy with 3-MA could notably abrogate growth of KDM6Bhigh THCA, but has mild influence on KDM6Blow THCA. Together, this study identified KDM6B as an essential epigenetic regulator for THCA, functioning as an autophagy regulator. The fundamental mechanisms underlying E2F1/KDM6B/TFEB axis provided novel vulnerabilities for THCA treatment.

Step-up fecal microbiota transplantation strategy: a pilot study for steroid-dependent ulcerative colitis.

BACKGROUND: The strategy of using fecal microbiota transplantation (FMT) for refractory ulcerative colitis (UC) remains unclear if single FMT failed to induce remission. This study aimed to evaluate the efficacy and safety of a designed step-up FMT strategy for the steroid-dependent UC. METHODS: Fifteen patients with steroid-dependent UC were enrolled, and treated with step-up FMT strategy. Follow-up clinical data was collected for a minimum of 3 months. Fecal microbiota composition before and post FMT of patients and related donors were analyzed by 16S rRNA sequencing. RESULTS: Eight of fourteen (57.1 %) patients achieved clinical improvement and were able to discontinue steroids following step-up FMT. One patient was lost to follow-up. Among the 8 patients who responded, five (35.7 %) received one FMT therapy, one (7.1 %) received two FMTs, and two (14.2 %) received two FMTs plus a scheduled course of steroids. Four (28.6 %) of the 8 patients who responded maintained long-term remission during follow-up (3-18 months). Six patients (42.9 %) failed to meet the criteria of clinical improvement and maintained steroid dependence, though three experienced transient or partial improvement. Microbiota analysis showed that FMT altered the composition greatly, and a microbiota composition highly similar to that of the donor emerged in the patients with successful treatment. No severe adverse events occurred during treatment and follow-up. CONCLUSIONS: Step-up FMT strategy shows promise as a therapeutic strategy for patients with steroid-dependent UC, likely due to the successful restructuring of gut microbial composition. TRIAL REGISTRATION: ClinicalTrials.gov, Number NCT01790061.

Comparative investigations on the biological effects of As (III) and As (V) in clam Ruditapes philippinarum using multiple biomarkers.

Inorganic arsenic is a known pollutant with two chemical forms, arsenite (As (III)) and arsenate (As (V)), in marine environment. Clam Ruditapes philippinarum is an important fishery species along the Bohai coast. In this study, the biological effects induced by the two arsenic chemical forms (arsenite and arsenate) were compared using multiple biochemical indices in the digestive glands of clam R. philippinarum. The production of reactive oxygen species, antioxidant enzyme activities and metabolic responses exhibited that both As (III) and As (V) induced immune, oxidative and osmotic stresses in clam digestive glands. The differential metabolic biomarkers, histidine and taurine, indicated the differential responsive mechanisms in osmotic regulation in clam digestive glands. In addition, both arsenic treatments enhanced the anaerobiosis metabolism in clam digestive glands. Overall, this work illustrated that arsenite and arsenate induced similar biological effects in clams, which might be accounted for the biological transformation of arsenate to arsenite in clams.

Effects of specialized nursing intervention based on quantitative assessment strategy on psychological state and quality of life of patients with senile dementia.

OBJECTIVES: To explore the effects of specialized nursing intervention based on quantitative evaluation strategy on the psychological state and quality of life of senile dementia patients. METHODS: 92 senile dementia patients were divided into the control and intervention groups (n = 46 each). Control group was given routine nursing intervention, while intervention group was given specialized nursing intervention based on the quantitative evaluation strategy. Patients' self-care ability, cognitive function, nursing compliance, psychological state, quality of life, and patient satisfaction indexes were measured. RESULTS: After nursing interventions, the self-care ability (71.73 ± 4.31 vs 63.82 ± 3.97 points) and cognitive functions such as orientation (7.96 ± 1.02 vs 6.53 ± 1.15), memory (2.16 ± 0.39 vs 1.69 ± 0.31), visual-spatial copying (3.78 ± 0.53 vs 3.02 ± 0.65), language skills (7.49 ± 1.26 vs 6.05 ± 1.28), and recall ability (2.13 ± 0.26 vs 1.75 ± 0.28) were significantly improved in the intervention group compared to the control group (P ˂ 0.05). The patient's compliance in the intervention group (95.65%) was prominently higher than the control group (80.43%) (P < 0.05). Notably, patient's psychological state (anxiety and depression) in the intervention group (47.42 ± 3.12 vs 51.39 ± 3.16, 48.52 ± 2.51 vs 52.83 ± 2.49) was better than the control group (P < 0.05). Furthermore, the quality of life was significantly improved in the intervention group (88.11 ± 1.11 vs 71.52 ± 1.24) compared to the control group (P < 0.05). Also, patients' satisfaction with nursing services in the intervention group (97.83%) was higher than the control group (78.26%) (P < 0.05). CONCLUSIONS: Specialized nursing intervention based on quantitative evaluation strategy can effectively improve patients' self-care ability, and cognitive function, reduce anxiety and depression and enhance the quality of life, which is worthy of clinical promotion and application.