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Immune system markers are related to mental functionality in the multiethnic cohort: Your Northern New york Examine.
Background The symptoms of coronavirus disease 2019 (COVID-19) range from moderate to critical conditions, leading to death in some patients, and the early warning indicators of the COVID-19 progression and the occurrence of its serious complications such as myocardial injury are limited. Methods We carried out a multi-center, prospective cohort study in three hospitals in Wuhan. Genome-wide 5-hydroxymethylcytosine (5hmC) profiles in plasma cell-free DNA (cfDNA) was used to identify risk factors for COVID-19 pneumonia and develop a machine learning model using samples from 53 healthy volunteers, 66 patients with moderate COVID-19, 99 patients with severe COVID-19, and 38 patients with critical COVID-19. Results Our warning model demonstrated that an area under the curve (AUC) for 5hmC warning moderate patients developed into severe status was 0.81 (95% CI 0.77-0.85) and for severe patients developed into critical status was 0.92 (95% CI 0.89-0.96). We further built a warning model on patients with and without myocardial injury with the AUC of 0.89 (95% CI 0.84-0.95). Conclusion This is the first study showing the utility of 5hmC as an accurate early warning marker for disease progression and myocardial injury in patients with COVID-19. Our results show that phosphodiesterase 4D and ten-eleven translocation 2 may be important markers in the progression of COVID-19 disease.Objective To identify ferroptosis-related molecular clusters, and to develop and validate a ferroptosis-based molecular signature for predicting biochemical recurrence-free survival (BCRFS) and tumor immune microenvironment of prostate cancer (PCa). Materials and Methods The clinical data and transcriptome data of PCa were downloaded from TCGA and GEO database. Ferroptosis-related genes (FRGs) were obtained from FerrDb database. We performed consensus clustering analysis to identify ferroptosis-related molecular subtypes for PCa. Univariate and multivariate Cox regression analysis were used to establish a ferroptosis-based signature for predicting BCRFS. Internal verification, external verification and subgroup survival analysis were then successfully performed. Results There was a total of 40 differentially expressed FRGs in PCa. We then identified three ferroptosis-related molecular clusters of PCa, which have significantly different immune infiltrating cells, tumor immune microenvironment and PD-L1 expressrisk score. The results of qRT-PCR successfully verified the mRNA expression levels of ASNS, GPT2, RRM2 and NFE2L2 in DU-145 and RWPE-1 cells while the results of IHC staining exactly verified the relative protein expression levels of ASNS, GPT2, RRM2 and NFE2L2 between PCa and BPH tissues. Conclusions This study successfully identified three ferroptosis-related molecular clusters. Besides, we developed and validated a novel ferroptosis-based molecular signature, which performed well in predicting BCRFS and tumor immune microenvironment of PCa.Bladder outlet obstruction (BOO) is a common urologic disease associated with poorly understood molecular mechanisms. This study aimed to investigate the possible involvements of circRNAs (circular RNAs) and circRNA-encoded proteins in BOO development. The rat BOO model was established by the partial bladder outlet obstruction surgery. Differential expression of circRNA and protein profiles were characterized by deep RNA sequencing and iTRAQ quantitative proteomics respectively. Novel proteins encoded by circRNAs were predicted through ORF (open reading frame) selection using the GETORF software and verified by the mass spectrometry in proteomics, combined with the validation of their expressional alterations by quantitative RT-PCR. Totally 3,051 circRNAs were differentially expressed in bladder tissues of rat BOO model with widespread genomic distributions, including 1,414 up-regulated, and 1,637 down-regulated circRNAs. Our following quantitative proteomics revealed significant changes of 85 proteins in rat BOO model, which were enriched in multiple biological processes and signaling pathways such as the PPAR and Wnt pathways. Among them, 21 differentially expressed proteins were predicted to be encoded by circRNAs and showed consistent circRNA and protein levels in rat BOO model. The expression levels of five protein-encoding circRNAs were further validated by quantitative RT-PCR and mass spectrometry. The circRNA and protein profiles were substantially altered in rat BOO model, with great expressional changes of circRNA-encoded novel proteins.Neuroblastoma (NB) is one of the most common solid tumors in children. Glycosyltransferases (GTs) play a crucial role in tumor development and immune escape and have been used as prognostic biomarkers in various tumors. However, the biological functions and prognostic significance of GTs in NB remain poorly understood. The expression data from Gene Expression Omnibus (GEO) and Therapeutically Applicable Research to Generate Effective Treatments (TARGET) were collected as training and testing data. Based on a progression status, differentially expressed GTs were identified. We constructed a GTscore through support vector machine, least absolute shrinkage and selection operator, and Cox regression in NB, which included four prognostic GTs and was an independent prognostic risk factor for NB. Patients in the high GTscore group had an older age, MYCN amplification, advanced International Neuroblastoma Staging System stage, and high risk. Samples with high GTscores revealed high disialoganglioside (GD2) and neuron-specific enolase expression levels. In addition, a lack of immune cell infiltration was observed in the high GTscore group. This GTscore was also associated with the expression of chemokines (CCL2, CXCL9, and CXCL10) and immune checkpoint genes (cytotoxic T-lymphocyte-associated protein 4, granzyme H, and granzyme K). A low GTscore was also linked to an enhanced response to anti-PD-1 immunotherapy in melanoma patients, and one type of tumor was also derived from neuroectodermal cells such as NB. In conclusion, the constructed GTscore revealed the relationship between GT expression and the NB outcome, GD2 phenotype, and immune infiltration and provided novel clues for the prediction of prognosis and immunotherapy response in NB.Members of the Protein Tyrosine Phosphatase (PTPs) family are associated with growth regulation and cancer development. Acting as natural counterpart of tyrosine kinases (TKs), mainly involved in crucial signaling pathways such as regulation of cell cycle, proliferation, invasion and angiogenesis, they represent key parts of complex physiological homeostatic mechanisms. Protein tyrosine phosphatase gamma (PTPRG) is classified as a R5 of the receptor type (RPTPs) subfamily and is broadly expressed in various isoforms in different tissues. PTPRG is considered a tumor-suppressor gene (TSG) mapped on chromosome 3p14-21, a region frequently subject to loss of heterozygosity in various tumors. However, reported mechanisms of PTPRG downregulation include missense mutations, ncRNA gene regulation and epigenetic silencing by hypermethylation of CpG sites on promoter region causing loss of function of the gene product. Inactive forms or total loss of PTPRG protein have been described in sporadic and Lynch syndrome colorectal cancer, nasopharyngeal carcinoma, ovarian, breast, and lung cancers, gastric cancer or diseases affecting the hematopoietic compartment as Lymphoma and Leukemia. Noteworthy, in Central Nervous System (CNS) PTPRZ/PTPRG appears to be crucial in maintaining glioblastoma cell-related neuronal stemness, carving out a pathological functional role also in this tissue. In this review, we will summarize the current knowledge on the role of PTPRG in various human cancers.Fracture healing is a complicated, long-term, and multistage repair process. Intermittent administration of parathyroid hormone (PTH) has been proven effective on intramembranous and endochondral bone formation during the fracture healing process, however, the mechanism is unclear. In this study, we investigated the role of exogenous PTH and endogenous PTH deficiency in bone fracture healing and explored the mechanism by using PTH knockout (PTH-/-) mice and ATDC5 cells. In a mouse femur fracture model, endogenous PTH deficiency could delay endochondral ossification whereas exogenous PTH promotes accumulation of endochondral bone, accelerates cartilaginous callus conversion to bony callus, enhances maturity of bony callus, and attenuates impaired fracture healing resulting from endogenous PTH deficiency. In fracture callus tissue, endogenous PTH deficiency could inhibit chondrocyte proliferation and differentiation whereas exogenous PTH could activate the IHH signaling pathway to accelerate endochondral ossification and rescue impaired fracture healing resulting from endogenous PTH deficiency. In vitro, exogenous PTH promotes cell proliferation by activating IHH signaling pathway on ATDC5 cells. In mechanistic studies, by using ChIP and luciferase reporter assays, we showed that PTH could phosphorylate CREB, and subsequently bind to the promoter of IHH, causing the activation of IHH gene expression. Therefore, results from this study support the concept that exogenous PTH 1-34 attenuates impaired fracture healing in endogenous PTH deficiency mice via activating the IHH pathway and accelerating endochondral ossification. Hence, the investigation of the mechanism underlying the effects of PTH treatment on fracture repair might guide the exploration of effective therapeutic targets for fracture.Phosphatidylcholine (PC) is produced via two distinct pathways in both hepatocytes and yeast, Saccharomyces cerevisiae. One of these pathways involves the sequential methylation of phosphatidylethanolamine (PE). In yeast cells, the methyltransferase, Cho2, converts PE to phosphatidylmonomethylethanolamine (PMME), which is further modified to PC by another methyltransferase, Opi3. On the other hand, free choline is utilized for PC production via the Kennedy pathway. The blockage of PC production is well known to cause endoplasmic reticulum (ER) stress and activate the ER-stress sensor, Ire1, to induce unfolded protein response (UPR). Here, we demonstrate that even when free choline is sufficiently supplied, the opi3Δ mutation, but not the cho2 Δ mutation, induces the UPR. The UPR was also found to be induced by CHO2 overexpression. Further, monomethylethanolamine, which is converted to PMME probably through the Kennedy pathway, caused or potentiated ER stress in both mammalian and yeast cells. We thus deduce that PMME per se is an ER-stressing molecule. Interestingly, spontaneously accumulated PMME seemed to aggravate ER stress in yeast cells. Collectively, our findings demonstrate the multiple detrimental effects of the low-abundance phospholipid species, PMME.Background and Aim To evaluate the clinical effect of ultrasound (US)-guided percutaneous thermal ablation of hepatic focal nodular hyperplasia (FNH). Methods A retrospective analysis of the clinical data of patients undergoing US-guided percutaneous thermal ablation of FNH from November 2008 to August 2021 at five medical centers in China was conducted. Results A total of 53 patients were included (26 males and 27 females). selleck The mean age was 35.1 ± 10.8 years. Sixty-five lesions (46 solitary cases and 7 cases with multiple lesions) were included, 70.8% (46/65) of which were located in the right liver lobe. The mean tumor length was 2.9 ± 1.5 cm. All patients successfully completed the ablation treatment. Immediate postoperative imaging showed that the primary technical success rate was 94.3% (50/53). Two patients underwent ablation 3 and 6 months after the primary ablation, and the secondary technical success rate was 100% (2/2). The incidence of complications was 3.8% (2/53). Imaging follow-up was conducted regularly after ablation, and no residual lesion enlargement or tumor recurrence was observed during the follow-up period.
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