Tychsenthygesen7127
tential drugs for glioblastoma therapy.
In this study, we provided a framework of workflow for potential therapeutic drug discovery and predicted 10 potential drugs for glioblastoma therapy.
The study evaluated the neuroprotective effect and pharmacokinetic profile of turmeric extract and their metabolites in the blood and brain in an aluminum-induced neurotoxic animal model.
Swiss albino mice received turmeric extract (TE), TE-essential oil combination (TE+EO) at doses of 25 and 50 mg/kg/day orally, vehicle (control), and a positive control group. Neurotoxicity was induced by injecting aluminum chloride (40 mg/kg/day, i.p.), and the effect of the intervention was studied for 45 days. The pharmacokinetic and behavioral biochemical markers of brain function and brain histopathological changes were evaluated.
The AUC 0-
showed a 30.1 and 54.2 times higher free curcumin concentration in plasma with 25 mg/kg and 50 mg/kg of TE+EO vs. TE, respectively. The concentration of free curcumin in the brain was 11.01 and 13.71-fold higher for 25 mg/kg and 50 mg/kg of TE+EO vs. TE, respectively. Aluminum impairs spatial learning and memory, which was significantly reversed with TE+EO by 28.6% (25 mg/kgtive diseases.As a newly discovered mechanosensitive ion channel protein, the piezo1 protein participates in the transmission of mechanical signals on the cell membrane and plays a vital role in mammalian biomechanics. Piezo1 has attracted widespread attention since it was discovered in 2010. In recent years, studies on piezo1 have gradually increased and deepened. In addition to the discovery that piezo1 is expressed in the respiratory, cardiovascular, gastrointestinal, and urinary systems, it is also stably expressed in cells such as mesenchymal stem cells (MSCs), osteoblasts, osteoclasts, chondrocytes, and nucleus pulposus cells that constitute vertebral bodies and intervertebral discs. They can all receive external mechanical stimulation through the piezo1 protein channel to affect cell proliferation, differentiation, migration, and apoptosis to promote the occurrence and development of lumbar degenerative diseases. Through reviewing the relevant literature of piezo1 in the abovementioned cells, this paper discusses the effect of piezo1 protein expression under mechanical stress stimuli on spinal degenerative disease, providing the molecular basis for the pathological mechanism of spinal degenerative disease and also a new basis, ideas, and methods for the prevention and treatment of this degenerative disease.
Early and accurate evaluation of severity and prognosis in acute pancreatitis (AP), especially at the time of admission is very significant. This study was aimed to develop an artificial neural networks (ANN) model for early prediction of in-hospital mortality in AP.
Patients with AP were identified from the Medical Information Mart for Intensive Care-III (MIMIC-III) database. Clinical and laboratory data were utilized to perform a predictive model by back propagation ANN approach.
A total of 337 patients with AP were analyzed in the study, and the in-hospital mortality rate was 11.2%. A total of 12 variables that differed between patients in survivor group and nonsurvivor group were applied to construct ANN model. Three independent variables were identified as risk factors associated with in-hospital mortality by multivariate logistic regression analysis. The predictive performance based on the area under the receiver operating characteristic curve (AUC) was 0.769 for ANN model, 0.607 for logistic regression, 0.652 for Ranson score, and 0.401 for SOFA score.
An ANN predictive model for in-hospital mortality in patients with AP in MIMIC-III database was first performed. The patients with high risk of fatal outcome can be screened out easily in the early stage of AP by our model.
An ANN predictive model for in-hospital mortality in patients with AP in MIMIC-III database was first performed. The patients with high risk of fatal outcome can be screened out easily in the early stage of AP by our model.
Infantile hemangiomas (IHs) are the most common benign tumors in infancy. The purpose of this study was to study the effects of propranolol on the function of human umbilical vein endothelial cells (HUVECs), in order to preliminarily elucidate the mechanism of propranolol in the treatment of IHs.
HUVECs were treated with different concentrations of propranolol (30
M, 60
M, 90
M, and 120
M) with or without VEGF. Their proliferation, migration, invasion, adhesion, and tube formation ability were tested by using CCK-8, wound healing assay, transwell, cell adhesion assay, and tube formation assay. The expressions of HUVECs angiogenesis signaling molecules pERK/ERK, pAKT/AKT, p-mTOR/mTOR, and pFAK/FAK were detected by Western blot.
Compared with the control group, propranolol could significantly inhibit the proliferation, migration, invasion, adhesion, and tube formation of HUVECs. Further studies showed that it could not only inhibit the migration, invasion, and tube formation ability of HUVECs after VEGF induction but also inhibit the phosphorylated protein expressions of angiogenesis-related signaling molecules like AKT, mTOR, ERK, and FAK in HUVECs, with a concentration-dependent inhibitory effect.
Propranolol can inhibit the proliferation, migration, invasion, adhesion, and tube formation of hemangioma endothelial cells; block VEGF-mediated angiogenesis signaling pathway; suppress the expressions of downstream angiogenesis-related signaling molecules; and ultimately achieve the effect of treatment of IHs.
Propranolol can inhibit the proliferation, migration, invasion, adhesion, and tube formation of hemangioma endothelial cells; block VEGF-mediated angiogenesis signaling pathway; suppress the expressions of downstream angiogenesis-related signaling molecules; and ultimately achieve the effect of treatment of IHs.Super enhancers (SEs) are large clusters of transcriptional activity enhancers, which drive and control the expression of cell identity genes, as well as differentiation of specific cell types. SEs have great application potential in pathogenic mechanism studies in developmental biology, cancer, and other diseases. However, the potential function and regulatory mechanism of SEs in the osteogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) are unknown. Therefore, this study investigated the potential function of SEs in the osteogenic differentiation of hBMSCs and their target genes. Osteogenesis was induced in three hBMSCs groups for 14 days. Further, ChIP-seq was performed on cells before and after osteogenic differentiation. Two target genes were then selected from cells before and after osteogenic differentiation for RT-qPCR. Finally, the selected SE target genes were analyzed by bioinformatics. In total, 1,680 SEs were identified in hBMSCs. After 14 days of osteogenic induction, onf target genes.Rheumatoid arthritis (RA) is a widespread inflammatory disease whose clinical manifestations are joint swelling, pain, and disability, affecting approximately 1% of individuals worldwide. Conventional anti-RA drugs currently used in clinic have severe side effects. The present study is aimed at investigating the antiarthritic effects of total saponins from Nigella glandulifera seeds (TSNGS) in rats with adjuvant-induced rheumatoid arthritis (AIA). Arthritis score, paw swelling, and body weight were monitored throughout the period of TSNGS treatment. The histopathological features and levels of cytokines, including IFN-γ, TNF-α, IL-1β, IL-4, IL-6, IL-10, and IL-17A, and OPG/RANKL signaling, were measured to determine the amelioration by TSNGS and its potential mechanisms on the inflammatory response and bone erosion. The differentiation of regulatory T cells (Tregs) in serum was assessed by flow cytometry. The results demonstrate that TSNGS at 10 mg/kg, 50 mg/kg, and 250 mg/kg inhibited AIA-induced clinical score, paw swelling, and histological changes. TSNGS reduced the immune-inflammatory reaction by restoring the secretion and expression of inflammatory cytokines and elevating the proportion of CD4+ CD25+ Tregs, accompanied by an increase in transcription factor Foxp3 levels. TSNGS also displayed bone protection by upregulation of the OPG/RANKL pathway. Collectively, TSNGS inhibited arthritis in AIA rats and so represents a potential novel treatment for RA.
Gummetal is a novel multifunctional alloy which possesses distinctive properties with the potential to refine and amend the efficacy of orthodontic treatment. The objective of this critical literature review was to investigate scientific evidence concerning the mechanical and clinical features of this recently manufactured beta-titanium orthodontic wire.
Electronic databases PubMed, PMC, Google Scholar, Ovid, and Cochrane Library were searched. Studies investigating the properties of Gummetal orthodontic wire including in vitro and clinical studies were selected, validity was assessed, and data was extracted. The risk of bias was assessed by the Cochrane risk of bias Tool 2.0 in a randomized clinical trial.
. Among 322 papers, 13 papers were selected and divided into two groups prospective double-blinded randomized clinical trial and in vitro studies.
The results of this review should be interpreted with caution because of the heterogeneity of the studies. Only single clinical trial paper was found inow fatigue limit, and high resilience have been confirmed. Gummetal provides lower force than Nitinol and TMA but higher than Supercable wire. Plastic deformation of Gummetal questions its superelasticity. Friction of Gummetal wire is comparable to SS and CoCr wires. Because of its nontoxic chemical composition, Gummetal might be useful in the initial phase of orthodontic treatment for patients suffering from nickel allergy. Further studies are necessary to assess the usefulness of Gummetal in the clinical practice.We intended to reformulate an existing platelet-derived wound healing formula to target each phase of the healing wound with the appropriate phase-specific molecules. A decreased perfusion of the skin, often associated with conditions such as thalassemia, sickle cell disease, diabetes mellitus, and chronic vascular disease, is the most common etiology of cutaneous ulcers and chronic wounds. We had previously shown that a PDWHF topically applied to a chronic nonhealing ulcer of a β-thalassemia homozygote stimulated and accelerated closure of the wound. The PDWHF was prepared from a pooled platelet concentrate of a matching blood group, consisting of a combination of platelet α-granule-derived factors. Processing of the apheresis-pooled platelets yielded various amounts of proteins (3.36 g/mL ± 0.25 (SD) (N = 10)) by the better lysis buffer method. Immunoglobulin G was found to be the most abundant α-granule-secreted protein. Equally broad quantities of the IgG (10.76 ± 12.66% (SD) (N = 10)) and IgG/albumin ratios (0.6 ± 0.4 (SD) (N = 10)) were quantified. We have developed a method using a reformulated lysis buffer followed by size exclusion chromatography and affinity chromatography to extract, identify, quantify, and purify IgG from activated platelets. IgG purification was confirmed by Western blot and flow cytometry. It was thought unlikely that the platelet IgG could be accounted for by adsorption of plasma protein, though the variable quantities could account for diversity in wound healing rates. The IgG could protect the wound even from subclinical infections and functionally advance healing. It may be useful in the management of skin ulcers in the early phase of wound healing.
