Osteoarthritis (OA) is a degenerative joint disease characterized by destruction of articular cartilage. The inflammatory response is the most important factor affecting the disease process. As ...interleukin‐1β (IL‐1β) stimulates several key mediators in the inflammatory response, it plays a major role in the pathogenesis of OA. Maslinic acid (MA) is a natural compound distributed in olive fruit. Previous studies have found that maslinic acid has an inhibitory effect on inflammation, but its specific role in the progression of OA disease has not been studied so far. In this study, we aim to assess the protective effect of MA on OA progression by in vitro and in vivo experiments. Our results indicate that, in IL‐1β‐induced inflammatory response, MA is effective in attenuating some major inflammatory mediators such as nitric oxide (NO) and prostaglandin E2, and inhibits the expression of IL‐6, inducible nitric oxide synthase, cyclooxygenase‐2, and tumor necrosis factor‐α (TNF‐α) in a concentration‐dependent manner. Also, MA downregulated the expression levels of thrombospondin motif 5 (ADAMTS5) and matrix metalloproteinase 13 in chondrocytes, resulting in reduced degradation of its extracellular matrix. Mechanistically, MA exhibits an anti‐inflammatory effect by inactivating the PI3K/AKT/NF‐κB pathway. In vivo, the protective effect of MA on OA development can be detected in a surgically induced mouse OA model. In summary, these findings suggest that MA can be used as a safe and effective potential OA therapeutic strategy.
Maslinic acid (MA) could prevent IL‐1β‐associated inflammation as well as extracellular matrix (ECM) degradation in human osteoarthritis (OA) chondrocytes. The potential mechanism involved in the protective effect of MA was that it could reverse inflammation‐related destruction via inhibiting PI3K/AKT/NF‐κB pathways activation. MA ameliorates OA progression in vivo via inhibiting the devastation of cartilage surface, cartilage calcification, and osteophytes formation.
Thermoset glass fiber-reinforced polymers (GFRP) have been widely used in manufacturing and construction for nearly half a century, but the large amount of waste produced by this material is ...difficult to dispose of. In an effort to address this issue, this research investigates the reuse of thermoset GFRP waste in normal strength concrete (NSC) and controlled low-strength materials (CLSM). The mechanical performance and workability of the resulting concrete were also evaluated. To prepare the concrete specimens, the thermoset GFRP waste was first pulverized into granular pieces, which were then mixed with cement, fly ash, and water to form cylindrical concrete specimens. The results showed that when the proportion of thermoset GFRP waste aggregate in the concrete increased, the compressive strengths of NSC and CLSM would decrease. However, when incorporating 5% GFRP waste into CLSM, the compressive strength was 7% higher than concrete without GFRP. However, the workability of CLSM could be improved to meet engineering standards by adding an appropriate amount of superplasticizer. This finding suggests that the use of various combinations of proportions in the mixture during production could allow for the production of CLSM with different compressive strength needs. In addition, the use of recycled thermoset GFRP waste as a new aggregate replacement for traditional aggregates in CLSM was found to be a more sustainable alternative to the current CLSM combinations used in the market.
Rapid phenotypic changes in traits of adaptive significance are crucial for organisms to thrive in changing environments. How such phenotypic variation is achieved rapidly, despite limited genetic ...variation in species that experience a genetic bottleneck is unknown. Capsella rubella, an annual and inbreeding forb (Brassicaceae), is a great system for studying this basic question. Its distribution is wider than those of its congeneric species, despite an extreme genetic bottleneck event that severely diminished its genetic variation. Here, we demonstrate that transposable elements (TEs) are an important source of genetic variation that could account for its high phenotypic diversity. TEs are (i) highly enriched in C. rubella compared with its outcrossing sister species Capsella grandiflora, and (ii) 4.2% of polymorphic TEs in C. rubella are associated with variation in the expression levels of their adjacent genes. Furthermore, we show that frequent TE insertions at FLOWERING LOCUS C (FLC) in natural populations of C. rubella could explain 12.5% of the natural variation in flowering time, a key life history trait correlated with fitness and adaptation. In particular, we show that a recent TE insertion at the 3′ UTR of FLC affects mRNA stability, which results in reducing its steady-state expression levels, to promote the onset of flowering. Our results highlight that TE insertions can drive rapid phenotypic variation, which could potentially help with adaptation to changing environments in a species with limited standing genetic variation.
This study aimed to assess the feasibility of utilizing geopolymer for repairing reinforced concrete beams. Three types of beam specimens were fabricated: benchmark specimens without any grooves, ...rectangular-grooved beams, and square-grooved beams. The repair materials employed included geopolymer material, and epoxy resin mortar, while carbon fiber sheets were used as reinforcement in select cases. The repair materials were applied to the rectangular and square-grooved specimens, with the carbon fiber sheets attached to the tension side of the specimens. To evaluate the flexural strength of the concrete specimens, a third-point loading test was conducted. The test results indicated that the geopolymer exhibited higher compressive strength and shrinkage rate compared to the epoxy resin mortar. Furthermore, the specimens reinforced with carbon fiber sheets demonstrated even greater strength than the benchmark specimens. In terms of flexural strength under cyclic third-point loading tests, the carbon fiber-reinforced specimens exhibited the ability to withstand over 200 cycles of repeated loading at 0.8 times the ultimate load. In contrast, the benchmark specimens could only withstand seven cycles. These findings highlight that the use of carbon fiber sheets not only enhances compressive strength but also improves resistance to cyclic loading.
Accumulation of evidence indicates that miRNAs have crucial roles in the regulation of EMT-associated properties, such as proliferation, migration and invasion. However, the underlying molecular ...mechanisms are not entirely illustrated. Here, we investigated the role of miR-296-5p in hepatocellular carcinoma (HCC) progression.
In vitro cell morphology, proliferation, migration and invasion were compared between HCC cell lines with up- or down-regulation of miR-296-5p. Immunofluorescence and Western blot immunofluorescence assays were used to detect the expression of EMT markers. Bioinformatics programs, luciferase reporter assay and rescue experiments were used to validate the downstream targets of miR-296-5p. Xenograft nude mouse models were established to observe tumor growth and metastasis. Immunohistochemical assays were conducted to study the relationships between miR-296-5p expression and Neuregulin-1 (NRG1)/EMT markers in human HCC samples and mice.
miR-296-5p was prominently downregulated in HCC tissues relative to adjacent normal liver tissues and associated with favorable prognosis. Overexpression of miR-296-5p inhibited EMT along with migration and invasion of HCC cells via suppressing NRG1/ERBB2/ERBB3/RAS/MAPK/Fra-2 signaling in vitro. More importantly, miR-296-5p disrupted intrahepatic and pulmonary metastasis in vivo. NRG1, as a direct target of miR-296-5p, mediates downstream biological responses. In HCC tissues from patients and mice, the levels of miR-296-5p and NRG1 also showed an inverse relationship.
miR-296-5p inhibited EMT-related metastasis of HCC through NRG1/ERBB2/ERBB3/RAS/MAPK/Fra-2 signaling.
Di-(2-ethylhexyl) phthalate (DEHP), an extensively used plasticizer, can cause environmental pollution and organ injury. Lycopene (LYC) is a natural carotene that has the potential to prevent chronic ...diseases. To reveal the effect of DEHP and/or LYC on the kidney, male mice were treated with LYC (5 mg/kg) and/or DEHP (500 mg/kg or 1000 mg/kg) by gavage for 28 days. The study indicated that DEHP caused glomerular atrophy, tubular expansion, disappearance of the mitochondrial membrane, and cristae rupture. DEHP exposure can increase the expression of aquaporin (AQP) subunits and the activity of Ca2+-Mg2+-ATPase and decrease the activity of Na+-K+-ATPase, which results in ion disorder. However, LYC can relieve kidney injury by regulating the activity of ATPase, the expression of ATPase subunits, and AQP subunit expression. The results indicated that AQP was a target for LYC in antagonizing the disturbance of DEHP-induced renal damage.
The present results indicated that AQP was a target for LYC to antagonize the disturbance of DEHP-induced renal ion homeostasis and renal injury. This research might provide a feasible molecular mechanism for LYC cotreatment of renal toxicity caused by DEHP. Display omitted
•DEHP exposure induced nephrotoxicity.•DEHP can cause the ions homeostasis imbalance.•DEHP caused the expression of AQP and ATPase activity disorder.•LYC can protect the organism from DEHP-induced nephrotoxicity.
To explore the risk factors for in-stent restenosis (ISR) after stent implantation in patients with coronary heart disease (CHD) using logistic regression analysis. From February 2020 to February ...2022, 350 patients with CHD after percutaneous coronary intervention (PCI) were divided into a stent stenosis group and a stent nonstenosis group based on coronary angiography results performed 2 years after PCI. Univariate and multivariate logistic regressions were used to analyze the factors related to ISR after coronary stent implantation in patients with CHD. This study was approved by the Ethics Committee of Shandong University of Traditional Chinese Medicine. Patient signed informed consent. Of the 350 patients with CHD, 138 (39.43%) had stent restenosis while 212 did not. Univariate analysis showed that a family history of CHD, history of type 2 diabetes, hypertension, smoking, and drinking, discontinuation of aspirin, use of conventional dose statins, calcified lesions, ≥ 3 implanted stents, stent length ≥ 30 mm, stent diameter < 3 mm, and tandem stent increased the risk of restenosis. The incidence of restenosis was higher in the stent group than that in the nonstent group (P < .05). There were no significant differences in the blood lipid level, left ventricular ejection fraction, clopidogrel/ticagrelor or beta-blocker withdrawal, location of culprit vessels, and thrombotic lesions between the 2 groups (P > .05). Multivariate logistic regression analysis showed that family history of CHD, history of type 2 diabetes, hypertension, smoking, and drinking, aspirin withdrawal, use of conventional doses of statins, calcified lesions, ≥ 3 implanted stents, stent length ≥ 30 mm, stent diameter < 3 mm, and tandem stenting were risk factors for ISR within 2 years after PCI. A family history of CHD, history of type 2 diabetes, hypertension, smoking, and drinking, discontinuation of aspirin, use of conventional dose statins, calcified lesions, ≥ 3 stent implantations, stent length ≥ 30 mm, stent diameter < 3 mm, and tandem stenting are risk factors for ISR within 2 years after PCI in patients with CHD.
The first catalytic asymmetric construction of the tryptanthrin skeleton has been established, taking advantage of a palladium(0)/chiral ligand-catalyzed enantioselective decarboxylative 4 + 2 ...cyclization of vinyl benzoxazinanones with isatins. This reaction has not only provided a direct and efficient method for constructing chiral tryptanthrin skeleta in high yields and excellent enantioselectivities (up to 97% yield, >99% ee) but also represents the first catalytic asymmetric decarboxylative cyclization of vinyl benzoxazinanones with isatins.
Our general purpose was to examine the effect of condensed Fuzheng extract (CFE) on the alleviation of immunosuppression. A mouse model of immunosuppression was established by intraperitoneal ...injection of CTX. A healthy control group received no CTX and no CFE; different intragastric doses of CFE were administered to three groups of mice for 28 days (4500, 2250, or 1125 mg/kg/day); a negative control received CTX alone, and a positive control received CTX and levamisole hydrochloride. We evaluated the effects of CFE on the immune system organs, cells, and molecules by comparing the different groups. CFE significantly improved immune system organs (spleen and thymus indices and histology), stimulated immune cell activities (number of white blood cells and lymphocytes, phagocytosis of mononuclear phagocytes, proliferation of splenic lymphocytes, antibody formation, and NK cell activity), and increased the levels of immunoglobulins (IgA, IgG, and IgM) and cytokines (IL‐2 and IFN‐γ). Thus CFE effectively alleviated CTX‐mediated immunosuppression and oxidative stress and enhanced the immunological functions of mice.
Cyclophosphamide is widely used but has many toxic and side effects, so we evaluated the immune organs, immune cells, and immune molecules to explore whether CFE has immune improvement effect.
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