Urantide alleviates atherosclerosis-related liver and kidney injury via the Wnt/ß-catenin signaling pathway in ApoE(-/-) mice.

OBJECTIVE: To investigate the role of urantide in the prevention and treatment of atherosclerosis (AS)-related liver and kidney injury by antagonizing the urotensin II/urotensin receptor (UII/UT) system and regulating the Wnt/ß-catenin signaling pathway. METHODS: Atherosclerotic ApoE-/- mice were treated with 20 mg/kg, 30 mg/kg, and 40 mg/kg urantide for 14 days. RESULTS: When ApoE-/- mice developed AS, significant pathological changes occurred in the liver and kidney, and the UII/UT system in tissue was highly activated; furthermore, the Wnt/ß-catenin signalling pathway was activated, and proteins related to this signalling pathway, such as GSK-3ß, AXIN2, CK­1, and APC, were significantly downregulated. After urantide treatment, the pathological damage to the liver and kidney was effectively improved, the activity of the UII/UT system was effectively inhibited, and the expression of the Wnt/ß-catenin signalling pathway and related proteins was restored. Wnt/ß-catenin signals were mainly localized in the cytoplasm, renal tubules, and interstitium. CONCLUSION: Urantide could improve AS-related liver and kidney injury by antagonizing the UII/UT system, and the improvements in liver and kidney function in atherosclerotic ApoE-/- mice may be related to inhibition of the Wnt/ß-catenin signalling pathway.

[Clinical Features of Neuromyelitis Optica Spectrum Disorders with Connective Tissue Diseases].

Objective To investigate the clinical features of neuromyelitis optica spectrum disorders(NMOSD)with connective tissue diseases(CTD). Methods Clinical data of 16 NMOSD-CTD patients and 54 NMOSD patients admitted to the Second Affiliated Hospital of Fujian Medical University from January 2015 to February 2020 were collected.The initial symptom,intracranial lesion,spinal cord lesion,laboratory examination and treatment response were compared between the two groups. Results The incidence of Sjögren's syndrome(SS)was the highest(10/16,62.5%)in NMOSD-CTD group.The NMOSD-CTD group had significantly higher positive rate of aquaporin-4 immunoglobulin G(AQP4-IgG)in serum or cerebrospinal fluid(100% vs. 70.2%,P=0.009),higher positive rates of serum anti-nuclear antibodies,anti Sjögren's syndrome A antibodies and anti-Ro52 autoantibodies(P<0.001),as well as higher proportion of patients with the expanded disability status scale score ≥ 6(50.0% vs. 22.2%,P=0.035)than the NMOSD group.There was no significant difference between the two groups in the age of onset,visiting age,recurrence frequency,disease course,distribution of intracranial lesions,spinal cord involvement,or the effective rate of glucocorticoid pulse therapy(all P>0.05).Conclusions NMOSD is often complicated with CTD,and SS is the most common one.The positive rate of serum or cerebrospinal AQP4-IgG and the seropositivity of several other autoantibodies in NMOSD-CTD patients were higher than those in NMOSD patients.Neurological impairment in NMOSD-CTD patients were severer,which should arouse attention of clinicians.

Novel drug candidates for treating esophageal carcinoma: A study on differentially expressed genes, using connectivity mapping and molecular docking.

Patients with esophageal carcinoma (ESCA) have a poor prognosis and high mortality rate. Although standard therapies have had effect, there is an urgent requirement to develop novel options, as increasing drug tolerance has been identified in clinical practice. In the present study, differentially expressed genes (DEGs) of ESCA were identified in The Cancer Genome Atlas and Genotype­Tissue Expression databases. Functional and protein­protein interaction (PPI) analyses were performed. The Connectivity Map (CMAP) was selected to predict drugs for the treatment of ESCA, and their target genes were acquired from the Search Tool for Interactions of Chemicals (STITCH) by uploading the Simplified Molecular­Input Line­Entry System structure. Additionally, significant target genes and ESCA­associated hub genes were extracted using another PPI analysis, and the corresponding drugs were added to construct a network. Furthermore, the binding affinity between predicted drug candidates and ESCA­associated hub genes was calculated using molecular docking. Finally, 827 DEGs (|log2 fold­change|≥2; q­value <0.05), which are principally involved in protein digestion and absorption (P<0.005), the plasminogen­activating cascade (P<0.01), as well as the 'biological regulation' of the Biological Process, 'membrane' of the Cellular Component and 'protein binding' of the Molecular Function categories, were obtained. Additionally, 11 hub genes were obtained from the PPI network (all degrees ≥30). Furthermore, the 15 first screen drugs were extracted from CMAP (score <­0.85) and the 9 second screen drugs with 70 target genes were extracted from STITCH. Furthermore, another PPI analysis extracted 51 genes, and apigenin, baclofen, Prestwick­685, menadione, butyl hydroxybenzoate, gliclazide and valproate were selected as drug candidates for ESCA. Those molecular docking results with a docking score of >5.52 indicated the significance of apigenin, Prestwick­685 and menadione. The results of the present study may lead to novel drug candidates for ESCA, among which Prestwick­685 and menadione were identified to be significant new drug candidates.