PSMAtargeted smallmolecule docetaxel conjugate Activity and preclinical analysis

BACKGROUND Spinal myxopapillary ependymoma (MPE) is a slow-growing tumor arising from ependymal cells of the central nervous system. MPE rarely presents with acute neurological compromise and most commonly occur in the filum terminale or conus medullaris region. To date, only a few cases have been reported of patients presenting acutely because of hemorrhagic MPE. CASE REPORT A 16-year-old boy without previous medical problems presented with a sudden onset of severe pain in the low back radiating to the thighs. #link# He could not walk owing to the severity of the pain. Neurological examination revealed an unsteady gait, but the rest of the motor and sensory examination was normal. Lumbosacral spine magnetic resonance imaging revealed an intradural hemorrhagic mass extending from L5 to S2. The encapsulated hemorrhagic tumor was resected, and the pathology was consistent with MPE grade I. The patient made a significant recovery postoperatively. It is extremely rare for MPE to present with spontaneous hemorrhage in the lumbosacral region. Prompt diagnosis and management led to a favorable outcome. This case report is intended to highlight the atypical presentation and imaging features of hemorrhagic MPE. CONCLUSIONS We described a rare case of MPE in the lumbosacral region of a patient who presented with acute neurological compromise and atypical imaging features.BACKGROUND Three-dimensional (3D) images can provide additional information on bone fractures, especially in patients with intra-articular distal radius fractures (DRFs). We aimed to identify possible risk factors for adverse outcomes using a 3D reconstruction technique. MATERIAL AND METHODS We retrospectively reviewed adult patients who underwent plaster immobilization with or without closed reduction for DRFs in our hospital between February 2016 and May 2019. The 3D reconstruction image of DRFs was viewed from multiple angles to determine the existence of gaps or steps. Then, a semiquantitative standard was used to assess the severity of fracture. The patients' basic data and radiographic data were collected, and multiple linear regression analyses were used to identify possible risk factors associated with adverse outcomes. RESULTS A total of 89 cases were analyzed in our study. There were 28, 39, and 22 patients with level 1, 2, or 3 fractures, respectively, based on the semiquantitative standard. In a multiple linear regression, preoperative severity degree (ß, 0.393; 95% confidence interval [CI], 0.260-0.526) and postoperative rehabilitation exercise (ß, 0.352; 95% CI, 0.023-0.681) were associated with the Patient-Rated Wrist Evaluation during follow-up. CONCLUSIONS Our study presents a new method based on 3D reconstruction images to assess the severity of intra-articular DRFs. Patients who were identified as having severe fractures based on this method were found to have worse functional outcome.The elastase, which belongs to the serine protease family, hydrolyses various proteins and may be involved in the parasite invasion. In this study, complete sequence of elastase-1 (TsE) the nematode Trichinella spiralis (Owen, 1835) was cloned into the plasmid pcDNA3.1 as TsE DNA vaccine. After intramuscular vaccination, serum anti-Trichinella antibodies (IgG and subclass IgG1/IgG2a, and IgA), total and specific intestinal mucosal sIgA in mice vaccinated with pcDNA3.1/TsE were measured by ELISA. The results showed that vaccination with pcDNA3.1/TsE induced a systemic humoral immune response (high levels of serum IgG and subclass IgG1/IgG2a and IgA) and local intestinal mucosal immune responses (high levels of TsE-specific sIgA). Vaccination of mice with TsE DNA vaccine also triggered a systemic and local concomitant Th1/Th2 response, as demonstrated by significant elevation of Th1 (IFN-γ and IL-2) / Th2 (IL-4 and IL-10) cytokine levels after the spleen, mesenteric lymph node and Peyer's patch cells from vaccinated mice were stimulated with recombinant TsE (rTsE). The vaccination of mice with pcDNA3.1/TsE displayed a 17% reduction of intestinal adult worms and a 39% reduction of muscle larvae. Our results indicated that TsE DNA vaccine elicited a systemic concomitant Th1/Th2 response and an enteral local sIgA response, and produced a partial protection against infection with T. spiralis. The TsE may be regarded as a potential candidate vaccine target against Trichinella infection. The oral polyvalent vaccines should be developed to improve the protective efficacy of anti-Trichinella vaccines.N6-methyladenosine(m6A) is the most abundant post-transcriptional RNA modification in eukaryotes. However, little is known about its role in pancreatic adenocarcinoma (PAAD). The aim of our study was to identify gene signatures and prognostic values of m6A regulators in PAAD. Patients from 3 different datasets with complete genomic and transcriptomic sequencing data were enrolled. Survival analysis for different gene alterations was performed using log-rank tests and Cox regression model. The association between alteration of m6A regulators and clinicopathological characteristics was examined using chi-square test. Results showed a high frequency of copy number alterations (CNAs) of m6A regulatory genes in PAAD patients, but somatic mutations were rarely happened. CNAs and mutations of m6A regulatory genes was associated with patient's gender, pathologic stage and resected tumor size. Patients with "gain of function" for m6A "reader" genes combined with copy number loss of "writers" or "erasers" had worse overall survival (OS) compared with other patterns. Moreover, copy number gain of m6A "reader" gene insulin growth factor 2 binding protein 2 (IGF2BP2) was an independent risk factor for OS (HR = 2.392, 95%CI 1.392-4.112, p less then 0.001) and disease-free survival (DFS) (HR = 2.400, 95%CI 1.236-4.659, p=0.010). link2 Gene Set Enrichment Analysis (GSEA) indicated that IGF2BP2 was correlated with multiple biological processes associated with cancer, of which the most significant processes were relevant to cancer cell cycle, cell immortalization and tumor immunity. To sum up, a significant relationship was found between m6A genomic alterations and worse clinical outcomes. These innovative findings are expected to guide further research on the mechanism of m6A in PAAD.Long alpha-synuclein gene (SNCA) promoter (Rep1) allele-carriers are linked to higher risk for Parkinson's disease (PD) and faster motor progression. Non-motor symptoms including autonomic, neuropsychiatric, and sleep disorders are common in PD. link3 However, the relationship between SNCA Rep1 microsatellite lengths and non-motor symptoms in early PD remains to be elucidated. 171 consecutive early PD patients were recruited from tertiary clinics and genotyped for Rep1. Multivariable regression analyses were performed to examine associations between Rep1 alleles and non-motor outcome scores. Longer Rep1 alleles significantly associated with higher total Non-Motor Symptom Scale (NMSS) scores (p=.006) and Hospital Anxiety and Depression Scale (HADS) depression subscale scores (p=.002), after adjusting for covariates and Bonferroni correction. We demonstrated that SNCA Rep1 allele length influences overall non-motor symptom burden and depression in early PD patients. Further functional studies to evaluate the role of Rep1 in non-dopaminergic systems may unravel new therapeutic targets for non-motor symptoms in PD.Epigenetic clocks are based on age-associated changes in DNA methylation of CpG-sites, which can accurately measure chronological age in different species. Recently, several studies have indicated that the difference between chronological and epigenetic age, defined as the age acceleration, could reflect biological age indicating functional decline and age-associated diseases. In humans, an epigenetic clock associated Alzheimer's disease (AD) pathology with an acceleration of the epigenetic age. In this study, we developed and validated two mouse brain region-specific epigenetic clocks from the C57BL/6J hippocampus and cerebral cortex. Both clocks, which could successfully estimate chronological age, were further validated in a widely used mouse model for AD, the triple transgenic AD (3xTg-AD) mouse. We observed an epigenetic age acceleration indicating an increased biological age for the 3xTg-AD mice compared to non-pathological C57BL/6J mice, which was more pronounced in the cortex as compared to the hippocampus. Genomic region enrichment analysis revealed that age-dependent CpGs were enriched in genes related to developmental, aging-related, neuronal and neurodegenerative functions. Due to the limited access of human brain tissues, these epigenetic clocks specific for mouse cortex and hippocampus might be important in further unravelling the role of epigenetic mechanisms underlying AD pathology or brain aging in general.
Previous studies have indicated that improvement in sleep duration might correlate with better cognition. We aimed to examine the associations between changes in sleep duration and cognitive function.
A change from short sleep duration (SSD) to moderate sleep duration (MSD) was associated with better global cognition scores (β=0.54,
<0.01). A change from SSD to long sleep duration (LSD) (β=-0.94,
<0.001) or a change from LSD to SSD (β=-1.38,
<0.01) was associated with lower global cognition. For individuals with MSD, a≥2 h increase (β=-0.89,
<0.001) or decrease (β=-0.70,
<0.001) in sleep duration was associated with lower global cognition.
For short sleepers, improvement in sleep duration correlated with better cognition. For long sleepers, there was no need to reduce sleep duration. Excessive changes or deviation from the moderate duration was associated with lower cognition.
Elafibranor clinical trial of 10325 individuals aged 45 and older from the China Health and Retirement Longitudinal Study (CHARLS) were included. Self-reported nocturnal sleep duration and cognitive function were assessed in the three waves of CHARLS from 2011 to 2015. Cognitive function was assessed by a global cognition score, which included episodic memory, visuospatial abilities, calculation, orientation and attention.
A total of 10325 individuals aged 45 and older from the China Health and Retirement Longitudinal Study (CHARLS) were included. Self-reported nocturnal sleep duration and cognitive function were assessed in the three waves of CHARLS from 2011 to 2015. Cognitive function was assessed by a global cognition score, which included episodic memory, visuospatial abilities, calculation, orientation and attention.Accumulating lines of evidence indicate that circular RNAs (circRNAs) are involved in the pathogenesis of human cancers, including nasopharyngeal carcinoma (NPC). However, the influences of hsa_circ_0081534 upon the pathogenesis and dynamics of NPC are undescribed. In this study, we identified a circRNA hsa_circ_0081534 was significantly upregulated in NPC tissues and cell lines. Inhibition of hsa_circ_0081534 induced a decrease in NPC cells proliferation and invasion in vitro, and repressed tumor growth in vivo. In mechanism, hsa_circ_0081534 promoted NPC progression by sponging miR-508-5p. Fibronectin 1 (FN1) is a target gene of miR-508-5p. In addition, rescue assays showed that FN1 overexpression (or miR-508-5p inhibitors) abolished the roles of hsa_circ_0081534 inhibition on NPC cells proliferation and invasion. Therefore, hsa_circ_0081534 promoted the proliferation, and invasion of NPC cells via regulating the miR-508-5p/FN1 axis. Our findings suggested that hsa_circ_0081534 could be a novel therapeutic target for the treatment of NPC patients.