Hartdegn8364
RNA-seq and gene ontology analysis indicated that cell proliferation and mTORC1 signaling were downregulated in KO hearts compared to WT hearts. In vivo BrdU labeling and immunofluorescence staining showed that myofibroblast proliferation in the Cilp1 KO heart was downregulated. Biaxial mechanical testing and ECM gene expression analysis indicated that while MI caused significant stiffness in WT hearts it had little effect on KO hearts. Upregulation of collagen expression after MI injury was attenuated in KO hearts. Recombinant CILP1 protein or NCilp1-conditioned medium promoted proliferation of neonatal rat ventricular cardiac fibroblasts via the mTORC1 signaling pathway. Conclusions Our studies established a pathological role of Cilp1 in promoting post-MI remodeling, identified a novel function of Cilp1 in promoting myofibroblast proliferation, and suggested that Cilp1 may serve as a potential biomarker for pathological cardiac remodeling and target for fibrotic heart disease.
Despite the lower rates of good outcomes and higher mortality in elderly patients, age does not modify the treatment effect of mechanical thrombectomy for large vessel occlusion strokes. We aimed to study whether racial background influences the outcome after mechanical thrombectomy in the elderly population.
We reviewed a prospectively maintained database of patients with acute ischemic stroke treated with mechanical thrombectomy from October 2010 through June 2020 to identify all consecutive patients with age ≥80 years and anterior circulation large vessel occlusion strokes. The patients were categorized according to their race as Black and White. Univariable and multivariable analyses were performed to define the predictors of 90-day modified Rankin Scale and mortality in the overall population and in each race separately.
Among 2241 mechanical thrombectomy, a total of 344 patients (median [interquartile range]; age 85 [82-88] years, baseline National Institutes of Health Stroke Scale score of 19 [15echanical thrombectomy for acute ischemic stroke, there was no racial difference in terms of outcome.
The status of the systemic right ventricular coronary microcirculation in hypoplastic left heart syndrome (HLHS) is largely unknown. It is presumed that the systemic right ventricle's coronary microcirculation exhibits unique pathophysiological characteristics of HLHS in Fontan circulation. The present study sought to quantify myocardial blood flow by cardiac magnetic resonance imaging and evaluate the determinants of microvascular coronary dysfunction and myocardial ischemia in HLHS.
One hundred nineteen HLHS patients (median age, 4.80 years) and 34 healthy volunteers (median age, 5.50 years) underwent follow-up cardiac magnetic resonance imaging ≈1.8 years after total cavopulmonary connection. Right ventricle volumes and function, myocardial perfusion, diffuse fibrosis, and late gadolinium enhancement were assessed in 4 anatomic HLHS subtypes. Myocardial blood flow (MBF) was quantified at rest and during adenosine-induced hyperemia. Coronary conductance was estimated from MBF at rest and catheter-based n suggest a potential benefit from early relief of frank cyanosis by total cavopulmonary connection.
The coronary microcirculation of the systemic ventricle in young HLHS patients shows significant differences compared with controls. These hypothesis-generating findings on HLHS-specific risk factors for microvascular dysfunction suggest a potential benefit from early relief of frank cyanosis by total cavopulmonary connection.
Thyroid hormone (TH) regulates metabolic pathways which may interfere with insulin action. There is limited knowledge on adipose tissue (AT) and skeletal muscle (SM) expression of genes associated with TH action in relation to insulin sensitivity. The aim of this study was to analyze AT and SM expression of the genes associated with TH action in subjects with different degree of insulin sensitivity and the regulation of these genes by insulin and free fatty acids (FFA).
The study group comprised 72 euthyroid male subjects, 36 normal-weight and 36 overweight/obese. Mycophenolatemofetil Two-hour hyperinsulinemic-euglycemic clamp and tissue biopsies were performed. In the subgroup of 20 subjects, 9 normal-weight and 11 overweight/obese, clamp was prolonged to 6h and another clamp with Intralipid/heparin infusion was performed after 1 week. Tissue biopsies were performed before and after each clamp.
Overweight/obese subjects had higher AT DIO2, DIO3, NCOR1, lower AT THRA and PPARGC1A, higher SM NCOR1 and lower SM DIO2, DIO3, PPARGC1A and ATP2A2 expression. In AT, DIO2 and PPARGC1A increased whereas NCOR1 and FOXO1 decreased after the clamp only in normal-weight individuals. DIO3 decreased in both groups. In SM, NCOR1 decreased whereas PPARGC1A and ATP2A2 increased after the clamp only in normal-weight individuals. Tissue THRA and THRB decreased in both groups. Intralipid/heparin abolished these effects.
Alterations in AT and SM expression of TH-related gene indicate a decreased tissue TH action in obesity. Inability to increase TH-related gene expression in obesity and during FFA oversupply may contribute to the aggravation of lipotoxicity.
Alterations in AT and SM expression of TH-related gene indicate a decreased tissue TH action in obesity. Inability to increase TH-related gene expression in obesity and during FFA oversupply may contribute to the aggravation of lipotoxicity.
Lubricin, a glycoprotein encoded by the proteoglycan 4 (PRG4) gene, is an essential boundary lubricant that reduces friction between articular cartilage surfaces. The loss of lubricin subsequent to joint injury plays a role in the pathogenesis of post-traumatic osteoarthritis (PTOA). Here we describe the development and evaluation of an adeno-associated virus (AAV)-based PRG4 gene therapy intended to restore lubricin in injured joints. The green fluorescent protein (GFP) gene was inserted the PRG4 gene to facilitate tracing the distribution of the transgene product (AAV-PRG4-GFP) in vivo.
Transduction efficiency of AAV-PRG4-GFP was evaluated in joint cells, and the conditioned medium containing secreted PRG4-GFP was used for shear loading/friction and viability tests. In vivo transduction of joint tissues following intra-articular injection of AAV-PRG4-GFP was confirmed in the mouse stifle joint in a surgical model of destabilization of the medial meniscus (DMM), and chondroprotective activity was tested ACLT model; however, data from the ACLT model suggest that early intervention is essential for efficacy.Design and fabrication of bifunctional efficient and durable noble-metal-free electrocatalyst for hydrogen and oxygen evolution is highly desirable and challenging for overall water splitting. Herein, a novel hybrid nanostructure with Ni2P/CoP nanoparticles decorated on a porous N-doped fullerene nanorod (p-NFNR@Ni-Co-P) was developed as a bifunctional electrocatalyst. Benefiting from the electric current collector (ECC) effect of FNR for the active Ni2P/CoP nanoparticles, the p-NFNR@Ni-Co-P exhibited outstanding electrocatalytic performance for overall water splitting in alkaline medium. To deliver a current density of 10 mA cm-2, the electrolytic cell assembled by p-NFNR@Ni-Co-P merely required a potential as low as 1.62 V, superior to the benchmark noble-metal-based electrocatalyst. Experimental and theoretical results demonstrated that the surface engineered FNR serving as an ECC played a critical role in accelerating the charge transfer during the electrocatalytic reaction. The present work paves the way for fullerene nanostructures in the realm of energy conversion and storage.Quinoa (Chenopodium quinoa Willd.) with a history of 5000 years as food is extremely rich in nutrients and bioactive compounds, including γ-aminobutyric acid (GABA), a natural four-carbon non-protein amino acid with great benefits to human health. In quinoa, GABA generally increases with the germination time, but the underlying molecular mechanism is unclear. Here, we found that the GABA content in quinoa varied significantly among 25 varieties using an automatic amino acid analyzer. Next, six varieties (three low-GABA and three high-GABA varieties) were used for further analyses. The content of GABA in six varieties all showed an increasing trend after germination. In addition, Pearson's correlation analysis showed that the changes in GABA content were closely related to the transcript level or enzyme activity of three key enzymes including glutamate decarboxylase (GAD), GABA transaminase (GABA-T), and succinate-semialdehyde dehydrogenase (SSADH) in the GABA shunt, especially GAD. Based on RNA-sequencing analysis, eight GAD genes, two GABA-T genes, one SSADH gene, nine polyamine oxidase (PAO) genes, five diamine oxidase (DAO) genes, four 4-aminobutyraldehyde dehydrogenase (BADH) genes, and three thermospermine synthase ACAULIS5 (ACL5) genes were identified. Among these, CqGAD8 and CqGABA-T2 may make a greater contribution to GABA accumulation during quinoa germination.Penispidins A-C (1-3), new aromatic sesquiterpenoids with two classes of rare carbon skeletons, were isolated from the endophytic fungus Penicillium virgatum HL-110. 1 represents the first example of a dunniane-type aromatic sesquiterpenoid, possessing a novel 4/6/6 tricyclic system, while (±)-2 and 3 have a 7,12-cyclized bisabolene skeleton, featuring a 3,4-benzo-fused 2-oxabicyclo[3.3.1]nonane central framework. Their structures were elucidated on the basis of spectroscopic methods, single-crystal X-ray diffraction, and ECD calculations. 1 inhibited hepatic lipid accumulation in HepG2 cells.Plant hormones, also called phytohormones, are small signaling molecules regulating a wide range of growth and developmental processes. These unique compounds respond to both external (light, temperature, water, nutrition, or pathogen attack) and internal factors (e.g., age) and mediate signal transduction leading to gene expression with the aim of allowing plants to adapt to constantly changing environmental conditions. Within the regulation of biological processes, individual groups of phytohormones act mostly through a web of interconnected responses rather than linear pathways, making elucidation of their mode of action in living organisms quite challenging. To further progress with our knowledge, the development of novel tools for phytohormone research is required. Although plenty of small molecules targeting phytohormone metabolic or signaling pathways (agonists, antagonists, and inhibitors) and labeled or tagged (fluorescently, isotopically, or biotinylated) compounds have been produced, the control over them in vivo is lost at the time of their administration. Caged compounds, on the other hand, represent a new approach to the development of small organic substances for phytohormone research. The term "caged compounds" refers to light-sensitive probes with latent biological activity, where the active molecule can be freed using a light beam in a highly spatio/temporal-, amplitude-, or frequency-defined manner. This review summarizes the up-to-date development in the field of caged plant hormones. Research progress is arranged in chronological order for each phytohormone regardless of the cage compound formulation and bacterial/plant/animal cell applications. Several known drawbacks and possible directions for future research are highlighted.
