Matzenferrell6495

Objective Increasing evidence highlights antisense long non-coding RNAs (lncRNAs) as promising therapeutic targets for cancers. Herein, this study focused on the clinical implications and functions of a novel antisense lncRNA PRKAG2-AS1 in hepatocellular carcinoma (HCC). Methods PRKAG2-AS1 expression was examined in a cohort of 138 HCC patients by RT-qPCR. Overall survival (OS) and disease-free survival (DFS) analyses were presented based on PRKAG2-AS1 expression, followed by ROCs. After silencing PRKAG2-AS1, cell proliferation was assessed via CCK-8, colony formation and EdU staining assays. Migrated and invasive capacities were assessed by wound healing and transwell assays. The relationships between PRKAG2-AS1, miR-502-3p and BICD2 were validated by luciferase reporter, RIP and RNA pull-down assays. The expression and prognostic value of BICD2 were analyzed in TCGA database. Results PRKAG2-AS1 was up-regulated in HCC than normal tissue specimens. High PRKAG2-AS1 expression was indicative of poorer OS and DFS time. Area under the curves (AUCs) for OS and DFS were 0.8653 and 0.7891, suggesting the well predictive efficacy of PRKAG2-AS1 expression. Targeting PRKAG2-AS1 distinctly inhibited proliferation, migration, and invasion in HCC cells. PRKAG2-AS1 was mainly expressed in cytoplasm of HCC cells. PRKAG2-AS1 may directly bind to the sites of miR-502-3p. Up-regulation of BICD2 was found in HCC tissues and associated with unfavorable prognosis. BICD2 was confirmed to be a downstream target of miR-502-3p. PRKAG2-AS1 could regulate miR-502-3p/BICD2 axis. Conclusion Our findings identified a novel lncRNA PRKAG2-AS1 that was associated with clinical implications and malignant behaviors. Thus, PRKAG2-AS1 could become a promising therapeutic target.Evidences have suggested that Sjogren's syndrome (SS) is associated with viral infection. The aim of this study was to investigate the involvement of respiratory viral poly(IC) in the pathogenesis of SS and potential mechanisms using a SS-like NOD/ShiLtJ (NOD) mouse model. 5-week female NOD mice were intratracheally administered poly(IC) every other day for 5 times to mimic viral infection. Pilocarpine induced saliva secretion was determined every 8 days. Submandibular glands (SMG) and lungs were harvested for the detection of pathological changes. We found that intratracheal administration of poly(IC) significantly advanced and enhanced the reduction of saliva flow rate in NOD mice. Furthermore, poly(IC) treatment aggravated the histopathological lesions and inflammatory cells infiltration in SMG. Accompanied by elevated expression of IFN cytokines and IL-33, Th1 activation was enhanced in SMG of poly(IC)-treated NOD mice, but Th17 cells activation was unchanged among the groups. In addition, intratracheal poly(IC) exposure promoted the expression of IL-33 and increased T cells proportion in the lung, which were consistent with the change in SMG. Therefore, intratracheal poly(IC) exposure aggravated the immunological and function disorder of SMG in NOD mice.Cellular exosome-mediated crosstalk in tumor microenvironment (TME) is a critical component of anti-tumor immune responses. In addition to particle size, exosome transport and uptake by target cells is influenced by physical and physiological factors, including interstitial fluid pressure, and exosome concentration. These variables differ under both normal and pathological conditions, including cancer. The transport of exosomes in TME is governed by interstitial flow and diffusion. Based on these determinants, mathematical models were adapted to simulate the transport of exosomes in the TME with specified exosome release rates from the tumor cells. In this study, the significance of spatial relationship in exosome-mediated intercellular communication was established by treating their movement in the TME as a continuum using a transport equation, with advection due to interstitial flow and diffusion due to concentration gradients. To quantify the rate of release of exosomes by biomechanical forces acting on thh. Quantifying the release of exosomes by cancer cells, their transport through the TME, and their concentration in TME will afford a deeper understanding of the mechanisms of these interactions and aid in deriving predictive models for therapeutic intervention.There is a critical need for safe treatment options to control inflammation in patients with systemic lupus erythematosus (SLE) since the inflammation contributes to morbidity and mortality in advanced disease. Endogenous neuroimmune mechanisms like the cholinergic anti-inflammatory pathway can be targeted to modulate inflammation, but the ability to manipulate such pathways and reduce inflammation and end organ damage has not been fully explored in SLE. Positive allosteric modulators (PAM) are pharmacological agents that inhibit desensitization of the nicotinic acetylcholine receptor (α7-nAChR), the main anti-inflammatory feature within the cholinergic anti-inflammatory pathway, and may augment α7-dependent cholinergic tone to generate therapeutic benefits in SLE. In the current study, we hypothesize that activating the cholinergic anti-inflammatory pathway at the level of the α7-nAChR with systemic administration of a partial agonist, GTS-21, and a PAM, PNU-120596, would reduce inflammation, eliminating the associated end organ damage in a mouse model of SLE with advanced disease. Further, we hypothesize that systemic α7 ligands will have central effects and improve behavioral deficits in SLE mice. Female control (NZW) and SLE mice (NZBWF1) were administered GTS-21 or PNU-120596 subcutaneously via minipumps for 2 weeks. We found that the increased plasma dsDNA autoantibodies, splenic and renal inflammation, renal injury and hypertension usually observed in SLE mice with advanced disease at 35 weeks of age were not altered by GTS-21 or PNU-120596. The anxiety-like behavior presented in SLE mice was also not improved by GTS-21 or PNU-120596. Although no significant beneficial effects of α7 ligands were observed in SLE mice at this advanced stage, we predict that targeting this receptor earlier in the pathogenesis of the disease may prove to be efficacious and should be addressed in future studies.Virulence arresting drugs (VAD) are an expanding class of antimicrobial treatment that act to "disarm" rather than kill bacteria. Despite an increasing number of VAD being registered for clinical use, uptake is hampered by the lack of methods that can identify patients who are most likely to benefit from these new agents. The application of pathogen genomics can facilitate the rational utilization of advanced therapeutics for infectious diseases. The development of genomic assessment of VAD targets is essential to support the early stages of VAD diffusion into infectious disease management. Genomic identification and characterization of VAD targets in clinical isolates can augment antimicrobial stewardship and pharmacovigilance. Personalized genomics guided use of VAD will provide crucial policy guidance to regulating agencies, assist hospitals to optimize the use of these expensive medicines and create market opportunities for biotech companies and diagnostic laboratories.Objective This study aimed to construct a prognostic ferroptosis-related signature for thyroid cancer and probe into the association with tumor immune microenvironment. Methods Based on the expression profiles of ferroptosis-related genes, a LASSO cox regression model was established for thyroid cancer. Kaplan-Meier survival analysis was presented between high and low risk groups. The predictive performance was assessed by ROC. The predictive independency was validated via multivariate cox regression analysis and stratified analysis. A nomogram was established and verified by calibration curves. The enriched signaling pathways were predicted via GSEA. The association between the signature and immune cell infiltration was analyzed by CIBERSORT. The ferroptosis-related genes were validated in thyroid cancer tissues by immunohistochemistry and RT-qPCR. Results A ferroptosis-related eight gene model was established for predicting the prognosis of thyroid cancer. Patients with high risk score indicated a poorer prognosis than those with low risk score (p = 1.186e-03). The AUCs for 1-, 2-, and 3-year survival were 0.887, 0.890, and 0.840, respectively. Following adjusting other prognostic factors, the model could independently predict the prognosis (p = 0.015, HR 1.870, 95%CI 1.132-3.090). A nomogram combining the signature and age was constructed. The nomogram-predicted probability of 1-, 3-, and 5-year survival approached the actual survival time. Several ferroptosis-related pathways were enriched in the high-risk group. The signature was distinctly associated with the immune cell infiltration. After validation, the eight genes were abnormally expressed between thyroid cancer and control tissues. Conclusion Our findings established a prognostic ferroptosis-related signature that was associated with the immune microenvironment for thyroid cancer.The aim of the present study was to investigate the effect of erythropoietin (EPO) on contrast-induced nephrology (CIN) in vivo and in vitro. Male C57BL/6J mice were divided into four groups control, CIN (iohexol 6.0 g/kg), EPO (3,000 IU/kg), and CIN+EPO. find more Hematoxylin and eosin (H&E) staining and biochemical index analyses were performed to evaluate renal injury. The cellular proliferation rate was detected using the Cell Counting Kit-8 (CCK-8) assay. In addition, a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and flow cytometric assay were used to assess the apoptosis of tissue and cells, respectively. Renal protein expression associated with apoptosis, pyroptosis, and signaling pathways was determined by Western blot (WB) assays for tissues and cells. The results showed that EPO significantly decreased serum creatinine, blood urea nitrogen, and cystatin C levels and alleviated renal histological changes in vivo. The protein levels of Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway components were overexpressed in the EPO treatment group. Furthermore, EPO suppressed the cell apoptosis and pyroptosis; decreased the protein levels of cleaved caspase-3, Bax, gasdermin D (GSDMD), and caspase-1; and enhanced the expression of Bcl-2. In summary, EPO could exert renoprotective effect by activating the JAK2/STAT3 signaling pathway, which may be a novel potential therapy for the treatment of CIN in the clinic.Objective To investigate the clinical characteristics of patients with dizziness/vertigo accompanied by loss of the posterior canal(s) (LPC). Methods Clinical data of 23 patients with LPC were collected. We determined video-head-impulse test (vHIT) gains of all six semicircular canals and correlated vHIT findings with other vestibulo-cochlear tests, including caloric test, ocular and cervical vestibular-evoked myogenic potentials (oVEMP, cVEMP), pure tone audiometry (PTA), and analyzed the differences in clinical manifestations of patients with LPC with different etiologies. Results LPC was identified in 23 patients. At the time of disease onset, most patients presented with dizziness (47.8%) and vertigo (30.4%) only, and some patients (21.7%) complained of unsteadiness. Among these 23 patients with LPC, there were 14 (60.9%) patients of isolated LPC (ILPC), 21 (91.3%) patients of unilateral LPC (ULPC), and 2 (8.7%) patients of bilateral LPC (BLPC). (1) Among 14 patients with ILPC, 13 (92.9%) patients had unilateral ILPC, the rate of ipsilesional impairment on caloric test, or oVEMP/cVEMP test or PTA ipsilesionally was 53.