Aguirregates9764
CircHECTD1 deficiency sensitized DB-treatment in DB-evoked AGS and HGC-27 cells. In vivo assay, circHECTD1 silencing led to the tumor reduction. Also, circHECTD1 served as miR-137 sponge in a sequence-complementary manner. Furthermore, transfection of miR-137 inhibitor markedly eliminated circHECTD1 absence-mediated promotion of DB-sensitivity in GC cells. Moreover, PBX3, a target of miR-137, play a DB-resistant role in GC cells. Fascinatingly, the deletion of PBX3 reversed the impact of miR-137 repression and circHECTD1 knockdown on DB-sensitivity in vitro.
CircHECTD1 served as an oncogene by a novel miR-137/PBX3 axis, which might supply an underlying biomarker for the diagnosis and prognosis of GC management.
CircHECTD1 served as an oncogene by a novel miR-137/PBX3 axis, which might supply an underlying biomarker for the diagnosis and prognosis of GC management.
The incidence of ischemic stroke in the context of vascular disease is high, and the expression of growth-associated protein-43 (GAP43) increases when neurons are damaged or stimulated, especially in a rat model of middle cerebral artery occlusion/reperfusion (MCAO/R).
DESIGN We bioengineered neuron-targeting exosomes (Exo) conjugated to a monoclonal antibody against GAP43 (mAb GAP43) to promote the targeted delivery of quercetin (Que) to ischemic neurons with high GAP43 expression and investigated the ability of Exo to treat cerebral ischemia by scavenging reactive oxygen species (ROS).
Our results suggested that Que loaded mAb GAP43 conjugated exosomes (Que/mAb GAP43-Exo) can specifically target damaged neurons through the interaction between Exo-delivered mAb GAP43 and GAP43 expressed in damaged neurons and improve survival of neurons by inhibiting ROS production through the activation of the Nrf2/HO-1 pathway. The brain infarct volume is smaller, and neurological recovery is more markedly improved following Que/mAb GAP43-Exo treatment than following free Que or Que-carrying exosome (Que-Exo) treatment in a rat induced by MCAO/R.
Que/mAb GAP43-Exo may serve a promising dual targeting and therapeutic drug delivery system for alleviating cerebral ischemia/reperfusion injury.
Que/mAb GAP43-Exo may serve a promising dual targeting and therapeutic drug delivery system for alleviating cerebral ischemia/reperfusion injury.Glioma is an extremely aggressive malignant neoplasm of the central nervous system. MicroRNA (miRNA) are known to bind to specific target mRNA to regulate post-transcriptional gene expression and are, therefore, currently regarded as promising biomarkers for glioma diagnosis and prognosis. The aim of the present study was to examine the pathogenesis and potential molecular markers of glioma by comparing the differential expression of miRNA and mRNA between glioma tissue and peritumor brain tissue. We explored the impact of screened core miRNA and mRNA on cell proliferation, invasion, and migration of glioma. An miRNA expression profile dataset (GSE90603) and a transcriptome profile dataset (GSE90598) were downloaded from combined miRNA-mRNA microarray chips in the Gene Expression Omnibus (GEO) database. Overall, 59 differentially expressed miRNAs (DEMs) and 419 differentially expressed genes (DEGs) were identified using the R limma software package. FunRich software was used to predict DEM target genes and mieffectively reversed the inhibition effects of miR-139-5p. These results demonstrate a novel axis for miR-139-5p/GABRA1 in glioma progression and provide potential prognostic predictors and therapeutic target for glioma patients.
Prickle planar cell polarity protein 1 (PRICKLE1), a core component of the non-canonical Wnt/planar cell polarity (PCP) pathway, was recently reported to be upregulated and correlated with poor prognosis in solid cancers. However, the effect of PRICKLE1 on acute myeloid leukemia (AML) remains unknown. This study aims to characterize the prognostic significance of PRICKLE1 expression in patients with AML.
RNA-seq was performed to compare mRNA expression profiles of AML patients and healthy controls. qRT-PCR and western blotting were used to analyze the expression of PRICKLE1 in AML patients and cell lines, and two independent datasets (TCGA-LAML and TARGET-AML) online were used to validate the expression results. The correlations between the expression of PRICKLE1 and clinical features were further analyzed.
Our data showed that PRICKLE1 expression levels were markedly high in AML patients at the time of diagnosis, decreased after complete remission and increased again at relapse. Of note, PRICKLE1 was highly expressed in drug resistant AML cells and monocytic-AML patients. HighPRICKLE1expression was found in FLT3/DNMT3A/IDH1/IDH2-mutant AML and associated with poor prognosis.Furthermore, high expression of PRICKLE1 may be correlated with migration and invasion components upregulation in AML patients.
These results indicated that highPRICKLE1expression may be a poor prognostic biomarker and therapeutic target of AML.
These results indicated that high PRICKLE1 expression may be a poor prognostic biomarker and therapeutic target of AML.
Job satisfaction refers to the feeling of contentment one experiences with their job. Job satisfaction among opticians is a crucial variable in determining their motivation and has consequential influence on the quality of eye health care, systems and services. Nevertheless, little has been done to assess job satisfaction levels among human resources for eye-health, such as opticians, in Ghana. This study assessed (for the first time) the job satisfaction level among opticians in Ghana, and the factors associated with their job satisfaction.
This was a cross-sectional survey involving all registered and licensed opticians working in Ghana. A validated, well-structured job satisfaction questionnaire was distributed to 195 opticians across all regions of the country. The questionnaire was composed of 15-item job satisfaction variables which were measured on a five-point Likert scale ('1-strongly disagree' to '5-strongly agree'). Logistic regression analyses were used to investigate the association between sy revision on ophthalmic healthcare administration in Ghana.
Majority of opticians working in Ghana were not satisfied with their jobs. Enhancing salary/remuneration would improve the job satisfaction level among opticians in the country. There is the need for effective management of human resources for eye-health (particularly opticians) and policy revision on ophthalmic healthcare administration in Ghana.Sport4Health Network (SPORT4H) is a multidisciplinary project co-funded by the European Union Erasmus+ programme aimed to encourage participation in physical activity in working population. SPORT4H includes educational and instructional activities that provide top-notch knowledge on various physical activities that may have an additional benefit to improve healthy lifestyle behaviours across workforce. The aims of Sport4Health 2021 e-symposium organized from 22nd to 23th March 2021 were to (1) summarize data collected during this project through evaluation of health and fitness profiles for over 40,000 employees from all Sport4HealthNet countries (Belgium, Bulgaria, Croatia, Netherlands, Serbia and Slovenia); (2) discuss the applicability of user-friendly guidelines for physical activity at workplace and e-learning module that includes multicomponent interventions with innovative activities; (3) share experiences from different partners about the effects of educational interventions in specific working environment; and, (4) overview challenges identified during the implementation of interventions at work settings. The Sport4Health 2021 e-symposium facilitated networking between partner institutions, provided practical information for extensive public education that advances physical activity at workplace, and capacitated interaction and recruitment of end-users through e-learning modules and guidelines.
As a significant cause of malignancy mortality, gastric carcinoma (GC) has been well documented to be an often-fatal diagnosis. Daurisoline Despite the limitations of effective therapy, immunotherapy has emerged as a promising therapeutic approach capable of killing cancer cells via the immune system. The current study was conducted to investigate the effect of cytokine C-C motif chemokine ligand 21 (CCL21) on GC progression through the metastasis-associated lung adenocarcinoma transcript 1/serine arginine-rich splicing factor 1/mammalian target of rapamycin (MALAT1/SRSF1/mTOR) axis.
Bioinformatics analysis was conducted to identify the key genes associated with GC and to subsequently predict their downstream genes. The effect of CCL21, MALAT1, and SRSF1 on the malignant phenotypes and epithelial-mesenchymal transition (EMT) of SGC-7901 and MGC-803 cells in-vitro and the tumorigenesis of SGC-7901 and MGC-803 cells in-vivo were assessed by expression determination and plasmid transfection. Additionally, RNA pull-down the key observations of our study provide evidence that CCL21 enhances the progression of GC via the MALAT1/SRSF1/mTOR axis, providing a novel therapeutic target for the treatment of GC.
The supergroup Euglenozoa unites heterotrophic flagellates from three major clades, kinetoplastids, diplonemids, and euglenids, each of which exhibits extremely divergent mitochondrial characteristics. Mitochondrial genomes (mtDNAs) of euglenids comprise multiple linear chromosomes carrying single genes, whereas mitochondrial chromosomes are circular non-catenated in diplonemids, but circular and catenated in kinetoplastids. In diplonemids and kinetoplastids, mitochondrial mRNAs require extensive and diverse editing and/or trans-splicing to produce mature transcripts. All known euglenozoan mtDNAs exhibit extremely short mitochondrial small (rns) and large (rnl) subunit rRNA genes, and absence of tRNA genes. How these features evolved from an ancestral bacteria-like circular mitochondrial genome remains unanswered.
We sequenced and assembled 20 euglenozoan single-cell amplified genomes (SAGs). In our phylogenetic and phylogenomic analyses, three SAGs were placed within kinetoplastids, 14 within diplonemids, one (EU2) within euglenids, and two SAGs with nearly identical small subunit rRNA gene (18S) sequences (EU17/18) branched as either a basal lineage of euglenids, or as a sister to all euglenozoans. Near-complete mitochondrial genomes were identified in EU2 and EU17/18. Surprisingly, both EU2 and EU17/18 mitochondrial contigs contained multiple genes and one tRNA gene. Furthermore, EU17/18 mtDNA possessedseveral features unique among euglenozoans including full-length rns and rnl genes, six mitoribosomal genes, and nad11,alllikely on a single chromosome.
Our data strongly suggest that EU17/18 is an early-branching euglenozoan with numerous ancestral mitochondrial features. Collectively these data contribute to untangling the early evolution of euglenozoan mitochondria.
Our data strongly suggest that EU17/18 is an early-branching euglenozoan with numerous ancestral mitochondrial features. Collectively these data contribute to untangling the early evolution of euglenozoan mitochondria.
It was estimated that over a billion people have a disability and around 110 to 190million experienced significant difficulties in functioning. Similarly, there were over 5million and 32,630 individuals with disability in Ethiopia and Addis Ababa, the capital city of Ethiopia, respectively. Health care is a human right, yet access barriers to healthcare remain one of the major challenges among people with disabilities. Community pharmacists are often the health system point of entry for most patients. Therefore, the aim of this study was to explore the barriers to community pharmacy service for individuals with physical, visual and hearing disability in Addis Ababa, Ethiopia.
A cross sectional phenomenological qualitative study design was employed to explore the barriers to community pharmacy service for individuals with Physical, Visual and Hearing disability. All members from Ethiopian National Association of the Blind (ENAB), Ethiopian National Association of the Deaf (ENAD) and Ethiopian National Association of persons with Physical Disability (ENAPPD) and all community pharmacy professionals in Addis Ababa were the study populations in this study.
