Hooperhagen4592

Nephrogenic diabetes insipidus (NDI) is characterized by impaired urinary concentrating ability, despite normal or elevated plasma concentrations of the antidiuretic hormone, arginine vasopressin (AVP). NDI can be inherited or acquired. NDI can result from genetic abnormalities, such as mutations in the vasopressin V2 receptor (AVPR2) or the aquaporin-2 (AQP2) water channel, or acquired causes, such as chronic lithium therapy. Congenital NDI is a rare condition. Mutations in AVPR2 are responsible for approximately 90% of patients with congenital NDI, and they have an X-linked pattern of inheritance. In approximately 10% of patients, congenital NDI has an autosomal recessive or dominant pattern of inheritance with mutations in the AQP2 gene. In 2% of cases, the genetic cause is unknown. The main symptoms at presentation include growth retardation, vomiting or feeding concerns, polyuria plus polydipsia, and dehydration. Without treatment, most patients fail to grow normally, and present with associated constipation, urological complication, megacystis, trabeculated bladder, hydroureter, hydronephrosis, and mental retardation. Treatment of NDI consist of sufficient water intake, low-sodium diet, diuretic thiazide, sometimes in combination with a cyclooxygenase (COX) inhibitor (indomethacin) or nonsteroidal anti-inflammatory drugs (NSAIDs), or hydrochlorothiazide in combination with amiloride. Some authors note a generally favorable long-term outcome and an apparent loss of efficacy of medical treatment during school age.Psoriasis is a chronic inflammatory skin disease whose etiology has not yet been determined. MicroRNAs (miRs) regulate the early stages of psoriasis and are targets for therapeutic intervention. The present study aimed to investigate the functional role of miR-489-3p in psoriasis. The present study first assessed the expression levels of miR-489-3p and Toll-like receptor (TLR)4 mRNA using reverse transcription-quantitative PCR, and also detected the protein expression levels of TLR4 and NF-κB via western blot analysis. TargetScan and miRDB target gene prediction tools were used to confirm the regulation of Toll-like receptor (TLR)4 by miR-489-3p. Moreover, a Cell Counting Kit (CCK)-8 assay was conducted to evaluate cell viability, while cell cycle and colony formation assays were performed to evaluate cell proliferation. Human keratinocytes (HaCaT) were co-transfected with TLR4-small interfering RNA and miR-489-3p-inhibitor plasmids, and analysis of cell proliferation and inflammatory cytokine secretion was performed using CCK-8 assay and ELISA. It was found that miR-489-3p expression was downregulated in patients with psoriasis. Bioinformatics analysis identified that TLR4 was a direct target of miR-489-3p. This was confirmed via luciferase reporter assays in HaCaT cells. The overexpression of miR-489-3p inhibited the TLR4/NF-κB signaling pathway and reduced cell proliferation. TLR4 silencing alleviated the effects of miR-489-3p, and enhanced cell proliferation and inflammatory cytokine secretion. Taken together, these data suggested that miR-489-3p may be a key effector of psoriasis, which promotes inflammatory responses by direct targeting of TLR4. miR-489-3p therefore represents a promising prognostic biomarker and therapeutic target for psoriasis treatment.Rosiglitazone is a synthetic peroxisome proliferator-activated receptor (PPAR)γ agonist widely used for the treatment of type 2 diabetes. Recent studies have demonstrated that rosiglitazone displays anti-inflammatory effects. The present study aimed to investigate whether rosiglitazone alleviates decreases in RAW264.7 cell viability resulting from lipopolysaccharide (LPS)-induced inflammation, as well as exploring the underlying mechanism. A macrophage inflammatory injury model was established by treating RAW264.7 cells with 100 ng/ml LPS. Cells were divided into LPS and rosiglitazone groups with different concentrations. Cell viability was assessed by performing an MTT assay. The expression of inflammatory cytokines was detected by conducting enzyme-linked immunosorbent assays and reverse transcription-quantitative PCR. Nitric oxidesecretion was assessed using the Griess reagent system. The expression levels of key nuclear factor-κB pathway-associated proteins were detected via western blotting. Rosiglitazone alleviated LPS-induced decrease in RAW264.7 cell viability and inhibited inflammatory cytokine expression in a concentration-dependent manner. Rosiglitazone significantly inhibited LPS-induced upregulation of p65 phosphorylation levels and downregulated IκBα expression levels. However, rosiglitazone-mediated inhibitory effects were reversed by PPARγ knockdown. The results of the present study demonstrated that rosiglitazone significantly inhibited LPS-induced inflammatory responses in RAW264.7 macrophage cells, which was dependent on PPARγ activation and NF-κB suppression.Thyroid cancer is the most common malignant tumor of the endocrine system. It has been reported that thymosin β10 (TMSB10) serves a vital role in tumor invasion and metastasis, and further understanding the role of TMSB10 in thyroid cancer may provide new insights into the development of novel targeted drugs. Bioinformatics analysis suggested that there might exist a regulatory relationship between miR-184 and TMSB10. Therefore, the expression of microRNA (miR)-184 was investigated in the TPC-1 and BCPAP thyroid cancer cell lines and the Nthy-ori 3-1 thyroid epithelial cell line via reverse transcription-quantitative PCR. The effect of miR-184 on BCPAP cell proliferation was evaluated using MTT and colony formation assays. In addition, the expression levels of epithelial-mesenchymal transition (EMT)-associated proteins were examined via western blot analysis and immunofluorescence staining. Furthermore, the targeting association between miR-184 and TMSB10 was verified using a dual-luciferase reporter assay. Notably, miR-184 overexpression attenuated BCPAP cell proliferation, increased the expression level of the epithelial marker E-cadherin, and decreased that of the mesenchymal marker vimentin. These effects were reversed in BCPAP cells following TMSB10 overexpression. The present study revealed that TMSB10 may be considered as a key mediator in promoting papillary thyroid carcinoma (PTC) cell proliferation and EMT, which were negatively regulated by miR-184. Therefore, the findings of the present study may provide a novel potential therapeutic target for attenuating PTC cell proliferation.Acute lymphocytic leukemia (ALL) is a type of childhood leukemia with the highest incidence; T-acute lymphocytic leukemia (T-ALL) is far more difficult to treat than B-acute lymphocytic leukemia (B-ALL) and has a poor long-term prognosis. Therefore, there is an urgent requirement to develop effective drugs for the treatment of T-ALL. Hirsutanol A is a natural sesquiterpenoid compound. The aim of the present study was to evaluate the in vitro anticancer activity of hirsutanol A against T-acute lymphocytic leukemia Jurkat cells and investigate the mechanism of action. A Cell Counting Kit-8 assay demonstrated that hirsutanol A inhibited the viability of Jurkat cells in a dose- and time-dependent manner. In addition, hirsutanol A induced cell cycle arrest at the G2 phase as determined via flow cytometry. Furthermore, Hoechst staining, Annexin V-FITC/propidium iodide double staining, mitochondrial membrane potential detection using JC-1 and western blot analysis of apoptotic proteins indicated that the inhibitory effect of hirsutanol A on Jurkat cells was associated with the induction of apoptosis. Of note, hirsutanol A induced the expression of the tumor suppressor p53, whereas simultaneous treatment with pifithrin-α, an inhibitor of p53, significantly reduced Jurkat cell apoptosis induced by hirsutanol A. In summary, the present study suggested that hirsutanol A inhibited Jurkat cell viability through induction of cell cycle arrest and p53-dependent initiation of apoptosis, thus hirsutanol may serve as a promising compound for the treatment of T-ALL.Long non-coding RNAs (lncRNAs) have been identified as a class of regulatory RNAs that participate in both physiological and pathological conditions, including acute kidney injury. However, the roles of lncRNA dysregulation in the pathogenesis of contrast-induced acute kidney injury (CI-AKI) are largely unknown. In the present study, the expression profiles of lncRNAs in kidney tissue were compared between rats with CI-AKI and controls using high-throughput RNA sequencing. In total, 910 differentially expressed (DE) lncRNAs (DElncRNAs), including 415 downregulated and 495 upregulated lncRNAs, were identified at 12 h after intra-arterial iodinated contrast medium injection (fold change ≥2; P less then 0.05). Eight DElncRNAs were further selected and validated using reverse transcription-quantitative polymerase chain reaction. A previous study defined microRNA (miRNA) and mRNA expression changes in the same CI-AKI model. In the present study, a lncRNA-mRNA co-expression network comprising 349 DElncRNAs and 202 DEmRNAs was constructed. The function of these DElncRNAs was mainly associated with oxidative stress and inflammation. Additionally, lncRNA-associated competing endogenous RNA (ceRNA) analysis revealed a network comprising 40 DElncRNA nodes, 5 DEmiRNA nodes and 59 DEmRNA nodes. Among which, the carnosine dipeptidase 1-specific and the transmembrane protein 184B-specific networks were likely to be associated with CI-AKI. The results of the present study revealed the expression profile and potential roles of lncRNAs in CI-AKI, and provide a framework for further mechanistic studies.Surgical treatment of gallbladder carcinoma remains challenging, while targeted therapy has been demonstrated to have potential. In the present study, the effect of signal transducer and activator of transcription 3 (STAT3) expression and vasculogenic mimicry (VM) on the occurrence and development of gallbladder carcinoma was evaluated. A total of 72 patients with gallbladder carcinoma and 10 patients with chronic cholecystitis were examined. Immunohistochemical staining was performed to determine the positive expression rates of STAT3. Periodic acid Schiff CD34 double staining was performed to detect VM in the gallbladder carcinoma group. STAT3 expression and VM in gallbladder carcinoma tissues was compared among patients with different clinical characteristics. In postoperative patients with gallbladder cancer, the relationship of the postoperative recurrence time with STAT3 expression and VM was assessed. STAT3 expression in gallbladder carcinoma tissue was significantly higher than that in cholecystitis tof tumor occurrence, development and metastasis. Therefore, STAT3 as a regulatory target, may inhibit the proliferation and invasion of tumor cells and block the development of VM, thereby representing a suitable target for antitumor angiogenesis therapy.In idiopathic membranous nephropathy, the complement membrane attack complex, more commonly referred to as complement 5b-9 (C5b-9), induces glomerular epithelial cell injury and proteinuria. C5b-9 can also activate numerous mechanisms that restrict or facilitate injury. Recent studies suggest that autophagy and the canonical Wnt signaling pathway serve an important role in repairing podocyte injury. However, the effect of C5b-9 on these pathways and the relationship between them remains unclear. The aim of the present study was to show the effect of C5b-9 on the Wnt/β-catenin signaling pathway and autophagy in podocytes in vitro. Levels of relevant indicators were detected by immunofluorescence staining and capillary western immunoassay. C5b-9 serum significantly activated the Wnt/β-catenin signaling pathway and promoted autophagy. Treatment with Dickkopf-related protein 1 (DKK1), a Wnt/β-catenin pathway blocker, protected podocytes from injury and significantly inhibited autophagy. The results indicated that inhibition of the Wnt/β-catenin pathway physiologically activated autophagy.