Alsalbertsen0445

Compelling evidence has demonstrated the potential functions of circular RNAs (circRNAs) in breast cancer (BC) tumorigenesis. JAK inhibition Nevertheless, the underlying mechanism by which circRNAs regulate BC progression is still unclear. The purpose of present research was to investigate the novel circRNA circRNF20 (hsa_circ_0087784) and its role in BC. CircRNA microarray sequencing revealed that circRNF20 was one of the upregulated transcripts in BC samples. Increased circRNF20 level predicted the poor clinical outcome in BC specimens. Functionally, circRNF20 promoted the proliferation and Warburg effect (aerobic glycolysis) of BC cells. Mechanistically, circRNF20 harbor miR-487a, acting as miRNA sponge, and then miR-487a targeted the 3'-UTR of hypoxia-inducible factor-1α (HIF-1α). Moreover, HIF-1α could bind with the promoter of hexokinase II (HK2) and promoted its transcription. In conclusion, this finding illustrates the vital roles of circRNF20 via the circRNF20/ miR-487a/HIF-1α/HK2 axis in breast cancer progress and Warburg effect, providing an interesting insight for the BC tumorigenesis.The effective treatment of bipolar disorder (BD) represents a significant unmet medical need. Although lithium remains a mainstay of treatment for BD, limited knowledge regarding how it modulates affective behavior has proven an obstacle to discovering more effective mood stabilizers with fewer adverse side effects. One potential mechanism of action of lithium is through inhibition of the serine/threonine protein kinase GSK3β, however, relevant substrates whose change in phosphorylation may mediate downstream changes in neuroplasticity remain poorly understood. Here, we used human induced pluripotent stem cell (hiPSC)-derived neuronal cells and stable isotope labeling by amino acids in cell culture (SILAC) along with quantitative mass spectrometry to identify global changes in the phosphoproteome upon inhibition of GSK3α/β with the highly selective, ATP-competitive inhibitor CHIR-99021. Comparison of phosphorylation changes to those induced by therapeutically relevant doses of lithium treatment led to the identification of collapsin response mediator protein 2 (CRMP2) as being highly sensitive to both treatments as well as an extended panel of structurally distinct GSK3α/β inhibitors. On this basis, a high-content image-based assay in hiPSC-derived neurons was developed to screen diverse compounds, including FDA-approved drugs, for their ability to mimic lithium's suppression of CRMP2 phosphorylation without directly inhibiting GSK3β kinase activity. Systemic administration of a subset of these CRMP2-phosphorylation suppressors were found to mimic lithium's attenuation of amphetamine-induced hyperlocomotion in mice. Taken together, these studies not only provide insights into the neural substrates regulated by lithium, but also provide novel human neuronal assays for supporting the development of mechanism-based therapeutics for BD and related neuropsychiatric disorders.Since online publication of this article, the authors noticed that some of the fly stocks were mislabelled in the methods and in Supplementary Figure 5. The corrected methods text is provided below.Renal fibrosis arises by the generation of matrix-producing fibroblasts and myofibroblasts through the epithelial-mesenchymal transition (EMT), a process in which epithelial cells undergo a transition into a fibroblast phenotype. A key feature of the EMT is the reorganization of the cytoskeletons, which may involve the Ca2+-binding protein S100A16, a newly reported member of the S100 protein family. However, very few studies have examined the role of S100A16 in renal tubulointerstitial fibrosis. In this study, S100A16 expression was examined by immunohistochemical staining of kidney biopsy specimens from patients with various nephropathies and kidney tissues from a unilateral ureteral obstruction (UUO) mouse model. Renal histological changes were investigated in S100A16Tg, S100A16+/-, and WT mouse kidneys after UUO. The expression of epithelia marker E-cadherin, mesenchymal markers N-cadherin, and vimentin, extracellular matrix protein, and S100A16, as well as the organization of F-actin, were investigated in S100A16 overexpression or knockdown HK-2 cells. Mass spectrometry was employed to screen for S100A16 binding proteins in HK-2 cells. The results indicated that S100A16 is high expressed and associated with renal tubulointerstitial fibrosis in patient kidney biopsies and in those from UUO mice. S100A16 promotes renal interstitial fibrosis in UUO mice. S100A16 expression responded to increasing Ca2+ and interacted with myosin-9 during kidney injury or TGF-β stimulation to promote cytoskeleton reorganization and EMT progression in renal tubulointerstitial fibrosis. Therefore, S100A16 is a critical regulator of renal tubulointerstitial fibroblast activation and is therefore a potential therapeutic target for the treatment of renal fibrosis.BACKGROUND Fibromyalgia syndrome (FMS) is a rheumatic disease characterized by diffuse body pain and decreased muscle function. The aim of the present study was to compare the biological rhythms of patients with fibromyalgia syndrome with the biological rhythms of healthy controls. MATERIAL AND METHODS This was a cross-sectional, single blind, and single center case-control study. The patients with fibromyalgia were evaluated using a Fibromyalgia Impact Questionnaire (FIQ), Biological Rhythms Interview of Assessment in Neuropsychiatry (BRIAN) Scale, Visual Analog Scale (VAS), Pittsburg Sleep Quality Index (PSQI) and Beck Depression Inventory (BDI). RESULTS The study included 77 female patients with FMS, and 32 healthy female individuals as the control group. We found that the patients in the FMS group achieved higher scores in VAS, BDI, PSQI, and the BRIAN scale than the patients in the control group (P less then 0.001). An evaluation of the relationship between FMS evaluation parameters and biological rhythm scores in patients with FMS revealed a significant positive correlation between total BRAIN and VAS, FIQ, BDI, and PSQI scores. When the relationship between FMS evaluation parameters and biological rhythm scores was evaluated in patients with FMS, a significant positive correlation was found between total BRAIN and VAS, FIQ, BDI, and PSQI scores (r=0.555, P less then 0.001; r=0.461, P less then 0.001; r=0.630, P less then 0.001; and r=0.551, P less then 0.001 respectively). CONCLUSIONS We consider that an evaluation of the biological rhythm of female patients with FMS, and appropriate treatment when required, would contribute significantly to the treatment and follow-up process of the patients.BACKGROUND Hypothermic machine perfusion (HMP) appears to exert a reconditioning effect on the ischemic damage of kidney grafts. However, some concerns still remain about its real effectiveness when it is delayed after a preliminary period of static cold storage (SCS) or with prolonged overall cold ischemia time (CIT). MATERIAL AND METHODS The effect of HMP on hemodynamic, metabolic, histological and ultrastructural features of grafts was investigated in 21 single-kidney grafts treated with a delayed HMP after SCS and with a total CIT of over 24 h. RESULTS The mean CIT, SCS, and HMP times were 29 h, 12 h, and 18 h, respectively. Longer SCS was associated with higher vascular resistance and lower arterial flow. In the pre- vs. post-HMP comparison, a significant decrease in arterial resistances and increase of flow were recorded. The hemodynamic improvement was independent of HMP duration. The perfused grafts retained some metabolic activity, with a statistically significant decrease of pH, pO2, and glucose levels, and increase of lactates in the perfusion liquid, by the end of HMP. Longer SCS was associated with higher pH and greater pO2 decrease during HMP. Light microscopy and transmission electronic microscopy revealed no significant variations in nuclear, cytoplasmic, or ultrastructural damage. SCS, HMP, and CIT were not identified as risk factor for delayed graft function or rejection. CONCLUSIONS A delayed and extended HMP can recover the graft hemodynamic function, maintain some metabolic activity, and stabilize the accumulated ischemic damage due to a preliminary SCS.BACKGROUND Cocaine abuse is a globally recognized problem with great socioeconomic and health impacts on society. We report a case of dissection of vertebral arteries and right renal artery after cocaine abuse that clinically presented as atypical headache and hypertension. CASE REPORT A 36-year-old male sought emergency care due to cervical pain after cocaine abuse. The pain was located to the right cervical side with irradiation to the homolateral temporal region. He had no previous comorbidities, except for cocaine abuse on a weekly basis. Angiotomography showed alterations compatible with recent arterial dissection of the right vertebral artery, confirmed on angioresonance. The patient received double anti-aggregation and antihypertensive drugs and was discharged. He was readmitted 5 days later due to hypertensive crisis and mild abdominal pain. Abdominal ultrasound with a Doppler of renal arteries showed signs right renal artery stenosis. Magnetic resonance angiography confirmed dissection of the same vessel. The patient underwent arteriography with stent implantation in the right renal artery. During outpatient follow-up, he progressed with gradual reduction of antihypertensive drugs. CONCLUSIONS There is only 1 case report correlating renal artery dissection with cocaine use and none with concomitant presentation of dissection in the vertebral and renal arterial beds. The scarcity of reports is a consequence of many problems. Therefore, young patients presenting with new-onset hypertension or abdominal pain and cocaine abuse history should raise suspicion for renal artery dissection. This case highlights the importance of clinical vigilance and routine specimen histopathology review, and explores key management considerations associated with the incidental diagnosis of Burkitt leukemia/lymphoma.Recently, hospitals and medical facilities have been experiencing a shortage of doctors along with heavy workload. The role of a mid-level provider may be important as a potential solution to these problems. A nurse practitioner(NP)is the most famous mid-level provider, and in our institution, the neurosurgery department has 3 NPs. Contrary to America, in Japan, the job of an NP is not an occupation independent from doctors or nurses. link2 NPs perform 38 specific procedures according to doctors' instructions. Their activities include assisting with operations, writing prescriptions, participation in neurosurgical rounds and conferences, transportation of patients by helicopter, etc. The safe transportation of patients to isolated islands by a helicopter is especially a representative activity in our institution. Inclusion of NPs in clinical settings may bring forth medical improvements and superior work efficiency. According to regional characteristics, the job profile of a NP presents a potential scope for added capabilities.INTRODUCTION Astroblastoma is a rare, supratentorial glial tumor, occurring predominantly in children and young adults. link3 However, treatment strategies have not yet been established for this rare disease. CASE PRESENTATION A 6-year-old boy presented with headache and nausea. CT and MRI revealed a left frontal mass lesion with slight edema and macrocalcifications. Gross tumor resection was performed. Histological examination found neoplastic cells with astroblastic characteristics, and a striking perivascular array of pseudorosettes. The final diagnosis was high-grade astroblastoma. MRI 13 months after surgery suggested local recurrence, and an enlargement was found 3 months later. Stereotactic radiotherapy(SRT)was performed. MRI after SRT showed enhanced cyst formation around the tumor bed, suggesting tumor recurrence. However, C-methionine PET/CT was useful to differentiate metastatic disease from radiation necrosis.