SOX8 Knockdown Overcomes Enzalutamide Resistance in Castration-Resistant Prostate Cancer by Inhibiting the Notch Signaling PathwayRead the full article
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Prognostic Value of GIMAP4 and Its Role in Promoting Immune Cell Infiltration into Tumor Microenvironment of Lung Adenocarcinoma
GIMAPs are recognized as an important regulator in the carcinogenesis and development of lung cancer, but the function of GIMAP4 in the tumor microenvironment (TME) of lung cancers is unclear. In this study, we investigated the expression and variation of GIMAP4 in lung adenocarcinoma (LUAD), to explore its association with infiltration of immune cells. The Cancer Genome Atlas (TCGA) data and Gene Expression Omnibus (GEO) data were analyzed. Infiltration of immune cells was identified with TIMER (Tumor Immune Estimation Resource) and TISIDB (an integrated repository portal for tumor-immune system interactions). GIMAP4 expression declined in non-small-cell lung cancer (NSCLC), correlated with a poor overall survival (OS) in LUAD, indicating that GIMAP4 was a promising prognostic biomarker in LUAD. GIMAP4 mutation frequency was 1.76% in TCGA cohort and was relevant to the expression of immune components. TIMER and CIBERSORT analysis further confirmed that high GIMAP4 expression possibly promoted immune cell infiltration into the TME, with low GIMAP4 impairing the efficacy of immunotherapies targeting common immune check point inhibitors (ICI). GO (Gene Ontology) and KEGG (Kyoto Encyclopedia of Genes and Genomes) analyses were performed to provide insights into biological processes involved in LUAD. GIMAP4 was expected to be a prognostic biomarker in LUAD and provides potential adjuvant or neoadjuvant therapeutic strategies for targeting ICIs.
Detection of Radiolabeled Inflammatory Cell Macrophage Subpopulations in Chronic Respiratory Diseases: Results from Preliminary Analyses
Chronic respiratory diseases (CRDs) like asthma and chronic obstructive pulmonary disease (COPD) are the leading causes of morbidity and mortality worldwide. Alveolar macrophages (AM) are immune cells that exist in different polarization states/phenotypes and have been shown to play a critical role during an inflammatory process. In this paper, differently polarized mouse bone marrow-derived macrophages (BMDM (M1-proinflammatory or M2-immunomodulator)) were radiolabeled with either 99mTc-D,L-hexamethylene-propyleneamine oxime (99mTc-HMPAO), 2-deoxy-2-[18F] fluoro-D-glucose (18F-FDG), or 67Ga-citrate. Biocompatibility and in vivo biodistribution of radionuclide-labeled macrophages after intravenous injection were evaluated. Radioactivity measurements were performed using Packard Cobra Quantum 5002 Gamma Counter. Both M1 and M2 macrophages showed a higher uptake for 18F-FDG and 99mTc-HMPAO, than 67Ga-citrate. M2 macrophages showed a higher uptake of radionuclides than M1 macrophages. The used radionuclides were biocompatible for both M1 and M2 macrophages. At 2-hour postinjection, 18F-FDG-labeled M1 and M2 macrophages were found significantly higher in the lung of inflammatory animals ( and , respectively) than in control mice. Labeling macrophages with either 18F-FDG or 99mTc-HMPAO did not affect their biodistribution. The results from these initial experiments indicate that radionuclide-labeled macrophages may allow a higher sensitivity detection in nuclear imaging techniques such as PET and SPECT. Further confirmatory studies are needed to noninvasively image radiolabeled BMDM to understand their role in the inflammatory processes inherent to CRDs.
Cleavage of AUF1 by Coxsackievirus B Affects DDX5 Regulatory on Viral Replication through iTRAQ Proteomics Analysis
Coxsackievirus B (CVB) 3C protease (3Cpro) plays a specific cleavage role on AU-rich binding factor (AUF1, also called hnRNP D), which consequently disputes the regulation of AUF1 on downstream molecules. In our study, the iTRAQ approach was first used to quantify the differentially expressed cellular proteins in AUF1-overexpressing HeLa cells, which provides straightforward insight into the role of AUF1 during viral infection. A total of 1,290 differentially expressed proteins (DEPs), including 882 upregulated and 408 downregulated proteins, were identified. The DEPs are involved in a variety of cellular processes via GO terms, protein–protein interactions, and a series of further bioinformatics analyses. Among the DEPs, some demonstrated important roles in cellular metabolism. In particular, DDX5 was further verified to be negatively regulated by AUF1 and increased in CVB-infected cells, which in turn promoted CVB replication. These findings provide potential novel ideas for exploring new antiviral therapy targets.
The Burden of Psoriasis in China and Global Level from 1990 to 2019: A Systematic Analysis from the Global Burden of Disease Study 2019
Objectives. Psoriasis is a skin disease thought to be related to immune system dysfunction. Our study is aimed at analyzing the prevalence of psoriasis in China in multiple different categories and compared the prevalence at the global level, in order to bring insights to policymakers for treating this disease. Methods. We analyzed psoriasis trends from 1990 to 2019 in China as well as around the globe with data from the Global Burden of Disease 2019 study. Multiple metrics such as age-standardized prevalence rates, percent change in age-standardized prevalence rates, disability-adjusted life years (DALYs), and age and sex patterns were included. We also predicted the trends of psoriasis prevalence and DALYs in the following 30 years. Results. In China, the age-specific prevalence cases showed a right shift in 2019 compared to 1990 with a peak between the ages of 50 and 54 years and an obvious surpass in males between 40 and 69. Though China still had the largest number of psoriasis cases in 2019, the increase rate was below global level. A positive linear relationship between psoriasis prevalence and comorbidities was seen with rheumatoid arthritis, diabetes mellitus, multiple sclerosis, nonrheumatic valvular heart disease, cardiomyopathy and myocarditis, nonmelanoma skin cancer, non-Hodgkin lymphoma, and multiple myeloma in China within the male group in 2019. Discussion. The burden of psoriasis, as measured by the absolute number of DALYs, continues to increase around the world. The scarcity of modifiable risks for most psoriasis burdens suggests that new knowledge is needed to develop effective prevention and treatment strategies.
Effects of Neurodynamic Mobilization on Health-Related Quality of Life and Cervical Deep Flexors Endurance in Patients of Cervical Radiculopathy: A Randomized Trial
Purpose. Cervical radiculopathy is disorder of cervical spinal nerve root affecting large number of population. Previously many studies are conducted to design suitable protocol for management of this disorder, but they lack in quality. The purpose of this study was to compare the effects of neural mobilization and cervical isometrics on health-related quality of life and deep flexors endurance in cervical radiculopathy. Methods. A double-blinded randomized clinical trial was conducted at Mayo Hospital, Lahore, Pakistan. Eighty-eight patients within the age range of 35-50 years were included in the study after taking their consent. In the experimental group (), median nerve mobilization was applied along with cervical isometric exercises. The control group () performed cervical isometric exercises alone. Muscle endurance was measured by craniocervical flexion test and quality of life on 36 items short form health survey SF-36 scale. Measurements were taken at baseline, at 2nd week, and at 4th week. For missing data, intention-to-treat analysis was used. Results. Within-group comparison with Friedman test showed a significant difference between pre, mid, and posttreatment scores on craniocervical flexion test and in all domains of SF 36 in both groups. While between-group comparison with Mann–Whitney U test showed all variables were similar at baseline but after 4 weeks there was a statistically significant improvement in craniocervical flexion test scores and all domains of SF 36 in the experimental group. But domain of pain showed mean rank of 49.43 after 4 weeks in the experimental group and 39.57 in the control group with and , while for all the other 7 domains values were and . Conclusion. Neural mobilization combined with cervical isometrics shows significant effects in improving quality of life and deep flexors endurance in patients with cervical radiculopathy than cervical isometrics alone.
Effects of Different Doses of Dex Anesthesia on Inflammatory Factors and Hemodynamics in Patients Undergoing Neurosurgery and Its Relationship with RSS Score
The effects of different doses of dexmedetomidine (Dex) anesthesia on inflammatory factors and hemodynamics in patients undergoing neurosurgery and its relationship with RSS scores are analyzed. A total of 102 patients who received neurosurgery in our hospital from March 2021 to March 2022 are selected. According to different intraoperative Dex dose, the enrolled patients are randomly divided into low-, medium-, and high-dose groups, 34 patients in each group. In this study, hemodynamic indexes, inflammatory factors, anesthesia effect, and the Ramsay sedation scale (RSS) score are compared in each groups. The experimental results show that in neurosurgery, compared with low-dose Dex, high-dose Dex can better maintain patients’ intraoperative hemodynamic parameters and effectively inhibit postoperative inflammatory response, but postoperative awakening time is also relatively prolonged, while medium-dose Dex can effectively control patients’ awakening time.