Magnussencooley5427
Extracellular vesicles (EVs) released by neurons and glia reach the cerebrospinal fluid (CSF). Studying the proteome of CSF-derived EVs offers a novel perspective on the key intracellular processes associated with the pathogenesis of the neurodegenerative disease amyotrophic lateral sclerosis (ALS) and a potential source from which to develop biomarkers.
CSF EVs were extracted using ultrafiltration liquid chromatography from ALS patients and controls. EV size distribution and concentration was measured using nanoparticle tracking analysis and liquid chromatography-tandem mass spectrometry proteomic analysis performed.
CSF EV concentration and size distribution did not differ between ALS and control groups, nor between a sub-group of ALS patients with or without an associated hexanucleotide repeat expansion (HRE) in
. Univariate proteomic analysis identified downregulation of the pentameric proteasome-like protein Bleomycin hydrolase in ALS patients, whilst Gene Ontology enrichment analysis demonstrated downregulation of proteasome core complex proteins (8/8 proteins, normalized enrichment ratio -1.77, FDR-adjusted
= 0.057) in the ALS group. The sub-group of ALS patients associated with the
HRE showed upregulation in Ubiquitin-like modifying-activating protein 1 (UBA1) compared to non-
cases.
Proteomic analysis of CSF EVs in ALS detects intracellular alterations in protein homeostatic mechanisms, previously only identified in pathological tissues. Selleckchem 2-Aminoethanethiol This supports the wider use of CSF EVs as a source of novel biomarkers reflecting key and potentially druggable pathological intracellular pathway alterations in ALS.
Proteomic analysis of CSF EVs in ALS detects intracellular alterations in protein homeostatic mechanisms, previously only identified in pathological tissues. This supports the wider use of CSF EVs as a source of novel biomarkers reflecting key and potentially druggable pathological intracellular pathway alterations in ALS.Considering the high socioeconomic costs related to the increasing number of dementia patients and their poor quality of life and that of their families, it is important to identify the condition early on and provide an appropriate intervention. This study organized a recollection-based occupational therapy program a nonpharmacological intervention consisting of five categories of activities (physical, horticultural, musical, art, and instrumental activity of daily living; IADL) and applied it to those having a mild stage of Alzheimer's disease. The experimental group participated in a total of 24 sessions--five times per week for one hour per session--while the control group took part in regular activities offered by the existing facilities. The experimental group presented improved cognitive functions, reduced depression, and enhanced quality of life; the two groups showed a statistically significant difference in every category. This study is meaningful in that it made a cognitive stimulation program concerning five different categories, implemented it for people suffering mild dementia, and confirmed positive outcomes. If a systemic version of the program is offered in dementia care facilities, it is expected to make a considerable contribution to the care of dementia patients.Play is considered the main occupation for children. Pediatric occupational therapists utilize play either for evaluation or intervention purpose. However, play is not properly measured by occupational therapists, and the use of play instrument is limited. This systematic review was aimed at identifying play instruments relevant to occupational therapy practice and its clinimetric properties. A systematic search was conducted on six databases (Academic Search Complete, CINAHL, MEDLINE, Psychology and Behavioral Science Collection, Scopus, and ASEAN Citation Index) in January 2020. The quality of the included studies was evaluated using Law and MacDermid's Appraisal for Clinical Measurement Research Reports, and psychometric properties of play instruments were evaluated using Terwee's checklist while the clinical utility is extracted from each instrument. Initial search identifies 1,098 articles, and only 30 articles were included in the final analysis, extracting 8 play instruments. These instruments were predominantly practiced in the Western culture, which consists of several psychometric evidences. The Revised Knox Preschool Play Scale is considered the most extensive and comprehensive play instrument for extrinsic aspect, whereas the Test of Playfulness + Test of Environmental Supportiveness Unifying Measure is a promising play instrument for intrinsic aspect on play, where both instruments utilize observation. My Child's Play is a potential questionnaire-based play instrument. However, the current development of play instruments in the occupational therapy field is immature and constantly evolving, and occupational therapists should exercise good clinical reasoning when selecting a play instrument to use in practice.
This research aimed to investigate the association between tumor necrosis factor-a-induced protein 8 (TNFAIP8) polymorphisms and ovarian cancer (OC) susceptibility.
A case-control study of 210 patients with OC and 231 healthy controls was conducted to assess the association between TNFAIP8 polymorphisms (rs11064, rs1045241, and rs1045242) and OC risk in Heilongjiang Province of China. The SNaPshot SNP assay was conducted to detect SNP genotype. Logistic regression analysis was applied to illustrate the underlying association.
Our research found that TNFAIP8 rs11064 and rs1045242 were significantly connected with the susceptibility of OC. Additionally, rs1045242 increased the risk of OC, while rs11064 performed a protective role in the risk of OC. Data revealed that rs1045242 strongly related with advanced FIGO stage, larger residual tumor, and the presence of recurrence.
TNFAIP8 genetic variants, which may play difference roles, were significantly associated with OC susceptibility. The underlying molecular mechanism needs be clarified with scientific evidence.
TNFAIP8 genetic variants, which may play difference roles, were significantly associated with OC susceptibility. The underlying molecular mechanism needs be clarified with scientific evidence.
Studies have shown that miR-502-5p functions as a tumor suppressor and is associated with tumor growth and metastasis. This study intends to uncover the potential mechanism of miR-502-5p functioning as a tumor suppressor in gastric cancer.
Expression levels of miR-502-5p and PD-L1 were measured by using qRT-PCR. Cell proliferation abilities were examined by EDU incorporation assay. Cell migration, invasion and cell cycle analysis of cells were determined by transwell assay, transwell-matrigel assay and flow cytometry, respectively. The relationship between miR-502-5p expression and the overall survival of xenograft tumor mice was statistically analyzed. Bioinformatics analysis and luciferase reporter assays were applied to analyze the relationship between miR-502-5p and CD40, STAT3 or PD-L1. Expressions of CD40, STAT3 and PD-L1 at protein level were detected by western blot.
The results showed that miR-502-5p was significantly downregulated in gastric cancer tumor tissues compared with adjacent normal tissues. Overexpression of miR-502-5p significantly attenuated the proliferation, migration/invasion and induced the G1 phase arrest of gastric cancer cells. Consistently, miR-502-5p suppressed tumor growth and metastasis in vivo. Mechanically, we demonstrated that miR-502-5p had inhibited the malignant behaviour of gastric cancer by down-regulating PD-L1 expression at transcriptional level and post-transcriptional levels.
These findings suggest that miR-502-5p acts as a tumor suppressor in gastric cancer (GC). MiR-502-5p/PD-L1 may be a novel therapeutic target in GC treatment.
These findings suggest that miR-502-5p acts as a tumor suppressor in gastric cancer (GC). MiR-502-5p/PD-L1 may be a novel therapeutic target in GC treatment.
We focused on the KCNQ1OT1/miR-15a/PD-L1 axis and explored its significance in regulating immune evasion and malignant behaviors of prostate cancer (PC) cells.
The expression levels of KCNQ1OT1, miR-15a, PD-L1, and CD8 in cells or tissues were examined by RT-qPCR, western blot or immunohistochemistry (IHC) assays. The direct regulations between KCNQ1OT1, miR-15a and PD-L1 were validated by luciferase reporter assay. PC cells were co-cultured with CD8
T cells to study the immune evasion. Proliferation, apoptosis, migration and invasion abilities were detected by MTT, flow cytometry, wound healing and Transwell assays, respectively. The cytotoxicity of CD8
T cells was determined by LDH cytotoxicity Kit. Epithelial-mesenchymal transition (EMT) and Ras/ERK signaling markers were evaluated by western blot.
KCNQ1OT1, PD-L1 and CD8 were increased, while miR-15a was decreased in PC tissues. MiR-15a directly bound to the 3'-UTR of PD-L1 and inhibited the expression of PD-L1. Overexpressing miR-15a in PC cells was sufficient to promote cytotoxicity and proliferation, while inhibit apoptosis of CD8
T cells, and also suppressed viability, migration, invasion and EMT while promoted apoptosis of PC cells. The above anti-tumor effects of miR-15a were reversed by overexpressing PD-L1. KCNQ1OT1 sponged miR-15a and released its inhibition on PD-L1. Functionally, KCNQ1OT1 in PC cells was essential for suppressing the cytotoxicity of CD8
T cells and maintaining multiple malignant phenotypes of PC cells. The Ras/ERK signaling was suppressed after overexpressing miR-15a or knocking down KCNQ1OT1.
LncRNA KCNQ1OT1 sponges miR-15a to promote immune evasion and malignant progression of PC via up-regulating PD-L1.
LncRNA KCNQ1OT1 sponges miR-15a to promote immune evasion and malignant progression of PC via up-regulating PD-L1.
Glioblastoma multiforme (GBM) is the most seriously brain tumor with extremely poor prognosis. Recent research has demonstrated that competitive endogenous RNA (ceRNA) network which long noncoding RNAs (lncRNAs) act as microRNA (miRNA) sponges to regulate mRNA expression were closely related to tumor development. However, the regulatory mechanisms and functional roles of ceRNA network in the pathogenesis of GBM are remaining poorly understood.
In this study, we systematically analyzed the expression profiles of lncRNA and mRNA (GSE51146 dataset) and miRNA (GSE65626 dataset) from GEO database. Then, we constructed a ceRNA network with the dysregulated genes by bioinformatics methods. The TCGA and GSE4290 dataset were used to confirm the expression and prognostic value of candidate mRNAs.
In total, 3413 differentially expressed lncRNAs and mRNAs, 305 differentially expressed miRNAs were indentified in GBM samples. Then a ceRNA network containing 3 lncRNAs, 5 miRNAs, and 60 mRNAs was constructed. The overall survival analysis of TCGA databases indicated that two mRNAs (C1s and HSD3B7) were remarkly related with the prognosis of GBM.
The ceRNA network may increase our understanding to the pathogenesis of GBM. In general, the candidate mRNAs from the ceRNA network can be predicted as new therapeutic targets and prognostic biomarkers for GBM.
The ceRNA network may increase our understanding to the pathogenesis of GBM. In general, the candidate mRNAs from the ceRNA network can be predicted as new therapeutic targets and prognostic biomarkers for GBM.
