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Grass carp hemorrhagic disease is a fatal disease caused by the grass carp reovirus (GCRV). The aberrant regulation of transcripts has been implicated in many types of diseases. In the present study, we characterized mRNA and miRNA transcriptomes of different virulent GCRVs using RNA sequencing (RNA-Seq). One hundred eighteen miRNAs were identified as being differentially expressed between different virulent viruses in grass carp fibroblasts. Chaetocin Eight miRNAs were selected to verify the RNA-Seq results using RT-PCR and mRNA methods. In total, 996 differentially expressed mRNA genes were identified in grass carp fibroblasts, while 901 miRNA-mRNA target pairs were observed to be inversely regulated in grass carp fibroblasts. link2 Integrated mRNA/miRNA expression profiling analysis results showed that the most influenced processes were the immune response and cell death. Three miRNAs were shown to exhibit the same expression patterns when two different methods were used and had important functions during viral infection. These results provide insights into the miRNA-mediated regulation of mRNA and valuable resources on transcript variation and regulation during GCRV infection, which are potentially useful for mechanistic and drug studies.Telmisartan (TLM) is a potent antihypertensive drug with pH-dependent aqueous solubility. This work aimed to enhance the solubility and dissolution rate of TLM by the co-amorphous drug amino acid (AA) approach by combining TLM, with different types and ratios of AAs. The co-amorphous TLM-AA blends were prepared by freeze-drying and investigated for solid-state characteristics like the dissolution rate enhancement of TLM. Among the prepared co-amorphous formulations, TLM-arginine (ARG) exhibited the greatest enhancement in solubility with increasing the molar ratio of ARG. The TLM-ARG at 12 ratio showed about a 57-fold increase in solubility of TLM and the highest dissolution percentage in phosphate buffer (pH7.5) (100% in 20 minutes) compared to both crystalline TLM (20% in 60 min) and physical mixture. Powder XRD, DSC, FTIR analysis and SEM demonstrated the formation of amorphous form within the co-amorphous formulations. Only TLMARG (10.5) were stable at (40°C, 75% RH) for a minimum of 90 days. In conclusion, ARG was able to stabilize the amorphous form of TLM and enhances its aqueous solubility and dissolution. The 12 w/w ratio of TLM-ARG co-amorphous showed the best solubility and dissolution rate while the 10.5 w/w ratio showed the best stability.
Severe and fulminant Clostridioides difficile infection (CDI) is associated with significant morbidity and mortality. While fecal microbiota transplantation (FMT) has proved to be a highly effective treatment for recurrent CDI, its efficacy in severe or fulminant CDI remains uncertain.
To perform a systematic review with meta-analysis evaluating clinical outcomes and safety of FMT in severe and fulminant CDI.
A systemic review with meta-analysis was performed through comprehensive search of Embase, Medline (Ovid), trial registers, and conference abstracts through January 2020. Studies on FMT in severe and fulminant CDI were included. Meta-analysis was done with random effects models given heterogeneity to estimate rates of cure, mortality, and colectomy. Publication bias was assessed using Egger’s test.
Sixteen studies comprised of one randomized controlled trial, four cohort studies, and eleven case series were analyzed. In total, 676 patients underwent FMT for severe or fulminant CDI. The overall rate of clinical cure after single FMT was 61.3% (95% CI 43.2-78.0%) with 10.9% (95% CI 0.2-30.2%) of patients experiencing major adverse events. The overall pooled colectomy rate after FMT was 8.2% (95% CI 0.1-23.7%) with a pooled all-cause mortality rate after FMT of 15.6% (95% CI 7.8-25.0%).
Low-quality data support the use of fecal microbiota transplantation in patients with severe and fulminant Clostridioides difficile infection.
Low-quality data support the use of fecal microbiota transplantation in patients with severe and fulminant Clostridioides difficile infection.Background Treatment related problems are any event or circumstance involving patient treatment that actually or potentially interferes with an optimum outcome for a patient. Hemodialysis patients have on average 5-6 comorbid conditions and require 8-12 medications each day making them vulnerable to treatment related problems. Objective This study aimed to investigate treatment related problems affecting Jordanian hemodialysis patients, as well as assessing the factors associated with them. Setting Three hemodialysis centers in Jordan. Method A cross sectional multi-centered study was conducted. Direct interviews and patient files were used to collect patient information. A validated data collection form was used. Main outcome measure The average number of treatment related problems per patient. Results 160 patients from three different Jordanian dialysis centers were included. The cohort was 53 ± 15.2 years old, been on dialysis for 5.9 ± 5.3 years, had 3.9 ± 1.8 comorbid conditions and took 10.2 ± 2.8 diffet related problems affecting this vulnerable population.The aim of this qualitative study was to explore and describe South African registered psychologists‘ account of their patients‘ myths regarding hypnotherapy. A social constructivist approach was employed to explore the descriptions of eight psychologists. This article converges on myths of participants‘ patients and where they originate from, as described by the participants. Psychologists were selected by means of chain referral sampling and engaged in one semi-structured interview. Data were analyzed by means of thematic analysis (TA), and participants elaborated on their experience of patients‘ myths and the possible origins thereof. Furthermore, conclusions were drawn across themes, which contributed to the findings. The most important finding indicated that while hypnotherapy is of great value, misconceptions stemming largely from unscientific applications contribute to patients‘ reluctance in utilizing this mechanism. The article concludes with a discussion of the implications, limitations and strengths of the study, as well as recommendations for future research.This study aims to investigate the inhibitory effect of microRNA-337 (miR-337) on osteogenic differentiation in bone marrow mesenchymal stem cells and its action of mechanisms. Overexpression and knockdown of miR-337 were performed in bone marrow mesenchymal stem cells (BMSCs). Cell proliferation was assessed by using a cell counting kit-8 (CCK-8), mineralization assay was performed by alizarin red staining, and alkaline phosphatase activity was then measured. Luciferase reporter assay was applied to verify miR-337 binding to Ras-related protein 1A (Rap1A) mRNA. Reverse transcription and quantitative polymerase chain reaction (RT-qPCR) was applied to measure the expressions of runt-related transcription factor 2 (Runx2), alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN), bone morphogenetic protein (BMP2), and miR-337. Then the protein level of Rap1A was determined by western blot analysis. High glucose inhibited osteogenic differentiation but increased the level of miR-337. Overexpression of miR-337 inhibited osteogenic differentiation in high glucose-treated BMSCs, while the knockdown of miR-337 reversed this process. Luciferase reporter assay confirmed that the presumed pairing binding site of miRNA-337 was in the 3′-UTR of the Rap1A WT. In addition, the knockdown of Rap1A distinctly repressed osteogenic differentiation, which blocked the effect of miR-337-knockdown on osteogenic differentiation in high glucose-treated BMSCs. MiR-337 could repress osteogenic differentiation in high glucose-treated BMSCs directly targeting Rap1A, thus provide a potential therapeutic strategy for patients with diabetic osteoporosis in clinic.The Yangtze River Delta White Goat is the only goat breed in the world that can produce superior-quality brush hair. Previous studies have shown that some genes are expressed differentially in the skin tissues between the goats produced superior-quality and normal-quality brush hair. Studies also have shown that different gene play varied roles in regulating the proliferation and apoptosis of hair follicle stem cells. However, the biological function of MAP3K1 (mitogen-activated protein kinase kinase kinase 1) gene in hair follicle stem cells is not fully understood. This study aims to investigate the role of MAP3K1 knockdown during the proliferation and apoptosis of hair follicle stem cells. RT-qPCR and Western blot were used to detect mRNA gene and protein expression level, CCK-8 and EdU assays were used to detect cell proliferation, and cell cycle and apoptosis were detected by flow cytometry. The results showed that the MAP3K1 expression level was significantly higher in the skin tissue of produced superior-quality brush hair than that in produced normal-quality brush hair. Moreover, functional studies indicated that si-MAP3K1 significantly inhibits the proliferation of hair follicle stem cells that came from a superior goat and promotes its apoptosis. Based on aforementioned assays, we speculated that MAP3K1 might play a regulatory effect in superior-quality brush hair traits.Although originally discovered inducing important biological functions in the nervous system, repulsive guidance molecule a (RGMa) has now been identified as a player in many other processes and diseases, including in myogenesis. RGMa is known to be expressed in skeletal muscle cells, from somites to the adult. Functional in vitro studies have revealed that RGMa overexpression could promote skeletal muscle cell hypertrophy and hyperplasia, as higher efficiency in cell fusion was observed. Here, we extend the potential role of RGMa during C2C12 cell differentiation in vitro. Our results showed that RGMa administrated as a recombinant protein during late stages of C2C12 myogenic differentiation could induce myoblast cell fusion and the downregulation of different myogenic markers, while its administration at early stages induced the expression of myogenic markers with no detectable morphological effects. We also found that RGMa effects on skeletal muscle hyperplasia are performed via neogenin receptor, possibly as part of a complex with other proteins. Additionally, we observed that RGMa-neogenin is not playing a role as an inhibitor of the BMP signalling in skeletal muscle cells. This work contributes to placing RGMa as a component of the mechanisms that determine skeletal cell fusion via neogenin receptor.Searching for an object in a complex scene is influenced by high-level factors such as how much the item would be expected in that setting (semantic consistency). There is also evidence that a person gazing at an object directs our attention towards it. However, there has been little previous research that has helped to understand how we integrate top-down cues such as semantic consistency and gaze to direct attention when searching for an object. Also, there are separate lines of evidence to suggest that older adults may be more influenced by semantic factors and less by gaze cues compared to younger counterparts, but this has not been investigated before in an integrated task. In the current study we analysed eye-movements of 34 younger and 30 older adults as they searched for a target object in complex visual scenes. link3 Younger adults were influenced by semantic consistency in their attention to objects, but were more influenced by gaze cues. In contrast, older adults were more guided by semantic consistency in directing their attention, and showed less influence from gaze cues.