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This study aimed to explore the effect of myricitrin on osteoblast differentiation in mice immortalised bone marrow mesenchymal stem cells (imBMSCs). Additionally, ovariectomy (OVX) mice were employed to examine the effect of myricitrin on bone trabecular loss in vivo. The effect of myricitrin on the proliferation of imBMSCs was evaluated using a cell counting kit-8 assay. Alizarin red staining, alkaline phosphatase staining were performed to elucidate osteogenesis. Furthermore, qRT-PCR and western blot determined the expression of osteo-specific genes and proteins. To screen for candidate targets, mRNA transcriptome genes were sequenced using bioinformatics analyses. Western blot and molecular docking analysis were used to examine target signalling markers. Moreover, rescue experiments were used to confirm the effect of myricitrin on the osteogenic differentiation of imBMSCs. OVX mice were also used to estimate the delay capability of myricitrin on bone trabecular loss in vivo using western blot, micro-CT, tartaric acid phosphatase (Trap) staining, haematoxylin and eosin staining, Masson staining and immunochemistry. In vitro, myricitrin significantly enhanced osteo-specific genes and protein expression and calcium deposition. Moreover, mRNA transcriptome gene sequencing and molecular docking analysis revealed that this enhancement was accompanied by an upregulation of the PI3K/AKT signalling pathway. Furthermore, copanlisib, a PI3K inhibitor, partially reversed the osteogenesis promotion induced by myricitrin. In vivo, western blot, micro-CT, hematoxylin and eosin staining, Masson staining, Trap staining and immunochemistry revealed that bone trabecular loss rate was significantly alleviated in the myricitrin low- and high-dose groups, with an increased expression of osteopontin, osteoprotegerin, p-PI3K and p-AKT compared to the OVX group. Myricitrin enhances imBMSC osteoblast differentiation and attenuate bone mass loss partly through the upregulation of the PI3K/AKT signalling pathway. Thus, myricitrin has therapeutic potential as an antiosteoporosis drug.
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Enfermedades Óseas Metabólicas , Osteogénesis , Animales , Femenino , Ratones , Diferenciación Celular , Células Cultivadas , Eosina Amarillenta-(YS)/farmacología , Simulación del Acoplamiento Molecular , Osteogénesis/genética , Ovariectomía , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN MensajeroRESUMEN
Bimetallic metal-organic frameworks (BMOFs) are a class of functional porous materials constructed by coordination between nodes containing two different metal ions and organic ligands. Studies have shown that the catalytic activity of BMOFs is greatly improved owing to the adjustment of charge distribution and the increase of active sites as well as the synergistic effect between the bimetals, and the advantages of their large specific surface area, high porosity, unique structure and dispersed active centres make them available as important organic materials applied in the field of wastewater treatment. In this review, the preparation and construction methods for BMOFs in recent years are summarized, and we focus on their removal of different types of pollutants in the aqueous environment, including ions, dyes, pharmaceuticals or personal care products, phenolic compounds and microorganisms, as well as their corresponding removal mechanisms. In addition, we provide an outlook on their future opportunities and challenges in wastewater treatment.
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Recently, short-fiber-reinforced thermoplastic composites (SFRTPCs) have been playing a more and more crucial role in the application of automotive interior materials due to their advantages of low density and environmental resistance properties. However, their relevant mechanical properties need to be optimized. Previous investigations revealed that the surface modification of fibers is useful to improve their mechanical properties. In this work, carbon fiber (CF)-reinforced polylactic acid (PLA) composites modified with MXene and graphene oxide (GO) were prepared by twin-screw extrusion and injection molding methods. Short CF was firstly modified with polyetherimide (PEI), then different weight ratios of MXene-GO (1:1) were subsequently modified on PEI-CF. Finally, the flexural properties and failure mechanisms were analyzed. The results showed that MXene-GO was successfully coated on CF surface, and the flexural strength and modulus of CF-PEI-MXene-GO-reinforced PLA (CF-PEI-MG/PLA) composite were improved compared to that of CF/PLA composite. In addition, the fracture sections of the composites were flat and white, and the fibers bonded well with PLA for CF-PEI-0.1MG/PLA composite compared to CF/PLA composite. The present study could provide a reference for further improving the mechanical performance of PLA-related composites.
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BACKGROUND: There are accumulating type 2 diabetes patients who have osteoporosis simultaneously. More effective therapeutic strategies should be discovered. Biochanin A (BCA) has been indicated that can play a role in improving metabolic disorders of type 2 diabetes and preventing osteoporosis. But whether BCA can treat type 2 diabetic osteoporosis has not been studied. PURPOSE: To investigate if the BCA can protect against type 2 diabetic osteoporosis and clarify the mechanism. METHODS: Micro-CT and histology assays were performed to detect the trabecular bone and analyze the bone histomorphology effect of BCA. CCK-8 assay was performed to detect the toxicity of BCA. TRAcP staining, immunofluorescence and hydroxyapatite resorption assay were used to observe osteoclasts differentiation and resorptive activity. Molecular docking provided evidence about BCA regulating the MAPK axis via prediction by the algorithm. QRT-PCR and Western Blotting were utilized to detect the expression of osteoclastogenesis-related markers and MAPK signaling pathway. RESULTS: Accumulation of bone volume after BCA treatment could be found based on the 3D reconstruction. Besides, there were fewer osteoclasts in db/db mice treated with BCA than db/db mice treated with saline. In vitro, we found that BCA hadn't toxicity in osteoclasts precursor, but also inhibited differentiation of osteoclasts. Further, we found that BCA suppresses osteoclastogenesis via ROS/MAPK signaling pathway. CONCLUSION: BCA can prevent type 2 diabetic osteoporosis by restricting osteoclast differentiation via ROS/MAPK signaling pathway.
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Diabetes Mellitus Tipo 2 , Osteogénesis , Animales , Ratones , Humanos , Simulación del Acoplamiento Molecular , Especies Reactivas de Oxígeno , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Transducción de SeñalRESUMEN
BACKGROUND: Iron homeostasis plays a positive role in articular cartilage health. Excessive iron or iron overload can induce oxidative stress damage in chondrocytes and ferroptosis cell death, advancing knee osteoarthritis (KOA). However, up to date, few effective agents treat iron overload-induced KOA (IOKOA). Chinese herbal medicine (CHM) provides abundant resources for drug selection to manage bone metabolic conditions, including osteoporosis. Biochanin A (BCA) is a novel bioactive multifunctional natural compound isolated from Huangqi, which has protective effects on bone loss. Nevertheless, the function and mechanism of BCA in treating IOKOA are still elusive. PURPOSE: This study seeks to uncover the potential therapeutic targets and mechanisms of BCA in the management of KOA with iron accumulation. METHODS: Iron dextrin (500 mg/kg) was intraperitoneally injected into mice to establish the iron overloaded mice model. OA was induced through surgery, and the progression was evaluated eight weeks following surgery. OA severity was evaluated with micro-CT and Safranin-O/Fast green staining in vivo. Iron deposition in the knee joint and synovium was assessed using Perl's Prussian blue staining. Ferric ammonium citrate (FAC) was then administered to primary chondrocytes to evaluate iron regulators mediated iron homeostasis. Toluidine blue staining was utilized to identify chondrocytes in vitro. The vitality of the cells was assessed using the CCK-8 test. The apoptosis rate of cells was measured using Annexin V-FITC/PI assay. The intracellular iron level was detected utilizing the calcein-AM test. Reactive oxygen species (ROS), lipid-ROS, and mitochondrial membrane potentiality were reflected via fluorescence density. Utilizing RT-qPCR and western blotting, the expression level was determined. RESULTS: Micro-CT and histological staining of knee joints showed greater cartilage degradation and higher iron buildup detected in iron-overloaded mice. BCA can reduce iron deposition and the severity of KOA. Toluidine blue staining and the CCK-8 assay indicated that BCA could rescue chondrocytes killed by iron. Cell apoptosis rates were increased due to iron overload but improved by BCA. Further, the intracellular content of iron, ROS, and lipid-ROS was increased with ferric ammonium citrate (FAC) treatment but restored after treatment with different concentrations of BCA. JC-1 staining revealed that BCA could reduce mitochondrial damage induced by iron overload. CONCLUSION: Iron overload was shown to promote chondrocyte ferroptosis in vivo and in vitro. Moreover, iron overload suppressed the expression of collagen II and induced MMP expression by catalyzing ROS generation with mitochondrial dysfunction. Our results showed that BCA could directly reduce intracellular iron concentration by inhibiting TfR1 and promoting FPN but also target the Nrf2/system xc-/GPX4 signaling pathway to scavenge free radicals and prevent lipid peroxidation. The results of this research indicate that BCA regulates iron homeostasis during the progression of osteoarthritis, which can open a new field of treatment for KOA.
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Sobrecarga de Hierro , Osteoartritis de la Rodilla , Animales , Ratones , Condrocitos/metabolismo , Hierro/metabolismo , Sobrecarga de Hierro/complicaciones , Sobrecarga de Hierro/tratamiento farmacológico , Sobrecarga de Hierro/metabolismo , Lípidos/farmacología , Osteoartritis de la Rodilla/patología , Especies Reactivas de Oxígeno/metabolismo , Cloruro de Tolonio/metabolismo , Cloruro de Tolonio/farmacologíaRESUMEN
Tenghuang Jiangu Capsule (THJGC) is a Chinese herbal formula used for the treatment of osteoporosis and osteoarthritis in China, but its mechanism for treating osteoporosis is not clear. The aim of this study was to investigate the therapeutic effect of THJGC on osteoporosis and its intrinsic mechanism through network pharmacology and experimental validation. Drugs and potential targets were obtained from several reliable databases through network pharmacology, and these targets were integrated and analyzed using bioinformatics and molecular docking strategies. Quercetin, lignans and kaempferol were identified as key components, and the key targets included Akt1, MAPKs, and CASP3. Subsequently, UPLC-MS/MS analysis confirmed the presence of components in THJGC for the treatment of osteoporosis. In addition, using ex vivo and in vivo models, it was confirmed that THJGC inhibited H2O2-induced ROS generation and apoptosis, and reduced OVX-induced bone loss in a mouse model of osteoporosis. Our data suggest that THJGC has antioxidant, bone formation-promoting, bone resorption-inhibiting, and MC3T3-E1 apoptosis-reducing effects, and thus has anti-osteoporotic properties. In conclusion, it may be a promising pharmacologic adjuvant treatment for osteoporosis.
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BACKGROUND: Metformin (MET) is widely used as a first-line hypoglycemic agent for the treatment of type 2 diabetes mellitus (T2DM) and was also confirmed to have a therapeutic effect on type 2 diabetic osteoporosis (T2DOP). However, the potential mechanisms of MET in the treatment of T2DOP are unclear. OBJECTIVE: To clarify the effect of MET in T2DOP and to explore the potential mechanism of MET in the treatment of T2DOP. METHODS: In vitro, we used MC3T3-E1 cells to study the effects of MET on osteogenic differentiation and anti-oxidative stress injury in a high glucose (Glucose 25 mM) environment. In vivo, we directly used db/db mice as a T2DOP model and assessed the osteoprotective effects of MET by Micro CT and histological analysis. RESULTS: In vitro, we found that MET increased ALP activity in MC3T3-E1 cells in a high-glucose environment, promoted the formation of bone mineralized nodules, and upregulated the expression of the osteogenesis-related transcription factors RUNX2, Osterix, and COL1A1-related genes. In addition, MET was able to reduce high glucose-induced reactive oxygen species (ROS) production. In studies on the underlying mechanisms, we found that MET activated the Nrf2/HO-1 signaling pathway and alleviated high-glucose-induced oxidative stress injury. In vivo results showed that MET reduced bone loss and bone microarchitecture destruction in db/db mice. CONCLUSION: Our results suggest that MET can activate the Nrf2/HO-1 signaling pathway to regulate the inhibition of osteogenic differentiation induced by high glucose thereby protecting T2DOP.
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Diabetes Mellitus Tipo 2 , Metformina , Osteoporosis , Animales , Ratones , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Glucosa/metabolismo , Hemo-Oxigenasa 1/metabolismo , Metformina/farmacología , Metformina/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , Osteoblastos , Osteogénesis , Osteoporosis/metabolismo , Estrés Oxidativo , Transducción de SeñalRESUMEN
Knee Osteoarthritis (KOA) is an age-related progressive degenerative joint disease, which is featured with pain, joint deformity, and disability. Accumulating evidence indicated oxidative stress plays a crucial role in the occurrence and development of KOA. Curcumin is a polyphenolic compound with significant antioxidant activity among various diseases while catalase (CAT) is an enzyme degrading hydrogen peroxide in treating oxidative diseases. We previously showed that the expression of CAT was low in cartilage. However, the combination of curcumin and CAT in KOA is still elusive. In this study, we demonstrated that the combination of curcumin and CAT has the potential to inhibit the IL1ß-induced chondrocyte apoptosis without cytotoxicity in vitro. Mechanistically, we found that the synergistic application curcumin and CAT not only promotes curcumin's regulation of the NRF2/HO-1 signaling pathway to enhance antioxidant enzyme expression to remove superoxide radicals, but also CAT can further remove downstream hydrogen peroxide which enhances the ability to scavenge reactive oxygen species (ROS). In vivo, studies revealed that combination of curcumin and catalase could better inhibit oxidative stress-induced chondrocyte injury by promoting the expression of ROS scavenging enzymes. In sum, the combination of curcumin and catalase can be used to treat KOA. Thus, combination of curcumin and catalase may act as a novel therapeutic agent to manage KOA and our research gives a rationale for their combined use in the therapeutic of KOA.
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Curcumina , Osteoartritis de la Rodilla , Humanos , Especies Reactivas de Oxígeno/metabolismo , Curcumina/uso terapéutico , Catalasa/metabolismo , Osteoartritis de la Rodilla/tratamiento farmacológico , Osteoartritis de la Rodilla/metabolismo , Peróxido de Hidrógeno/farmacología , Condrocitos/metabolismo , Estrés Oxidativo , Antioxidantes/farmacología , Antioxidantes/metabolismo , Factor 2 Relacionado con NF-E2/metabolismoRESUMEN
Iron overload is a prevalent pathological factor observed among elderly individuals and those with specific hematological disorders, and is frequently associated with an elevated incidence of osteoporosis. Although arctiin (ARC) has been shown to possess antioxidant properties and the ability to mitigate bone degeneration, its mechanism of action in the treatment of iron overloadinduced osteoporosis (IOOP) remains incompletely understood. To explore the potential molecular mechanisms underlying the effects of ARC, the MC3T3E1 cell osteoblast cell line was used. Cell Counting Kit was used to assess MC3T3E1 cell viability. Alkaline phosphatase staining and alizarin red staining were assessed for osteogenic differentiation. Calcein AM assay was used to assess intracellular iron concentration. In addition, intracellular levels of reactive oxygen species (ROS), lipid peroxides, mitochondrial ROS, apoptosis rate and mitochondrial membrane potential changes in MC3T3E1 cells were examined using flow cytometry and corresponding fluorescent dyes. The relationship between ARC and the PI3K/Akt pathway was then explored by western blotting and immunofluorescence. In addition, the effects of ARC on IOOP was verified using an iron overload mouse model. Immunohistochemistry was performed to evaluate expression of osteogenesisrelated proteins. Micro-CT and H&E were used to analyze bone microstructural parameters and histomorphometric indices in the bone tissue. Notably, ARC treatment reversed the decreased viability and increased apoptosis in MC3T3E1 cells originally induced by ferric ammonium citrate, whilst promoting the formation of mineralized bone nodules in MC3T3E1 cells. Furthermore, iron overload induced a decrease in the mitochondrial membrane potential, augmented lipid peroxidation and increased the accumulation of ROS in MC3T3E1 cells. ARC not only positively regulated the antiapoptotic and osteogenic capabilities of these cells via modulation of the PI3K/Akt pathway, but also exhibited antioxidant properties by reducing oxidative stress. In vivo experiments confirmed that ARC improved bone microarchitecture and biochemical parameters in a mouse model of iron overload. In conclusion, ARC exhibits potential as a therapeutic agent for IOOP by modulating the PI3K/Akt pathway, and via its antiapoptotic, antioxidant and osteogenic properties.
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Sobrecarga de Hierro , Osteoporosis , Humanos , Ratones , Animales , Anciano , Proteínas Proto-Oncogénicas c-akt/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Antioxidantes/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Osteogénesis , Sobrecarga de Hierro/complicaciones , Sobrecarga de Hierro/tratamiento farmacológico , Sobrecarga de Hierro/metabolismo , Osteoporosis/tratamiento farmacológico , Osteoporosis/etiología , Osteoblastos/metabolismoRESUMEN
Iron homeostasis plays an essential role in joint health, while iron overload can cause damage and death of cartilage cells. Cardamonin (CAR) is a substance found in the fruit of the chasteberry plant and has anti-inflammatory and anti-tumor activities. We first administered iron dextran (500 mg/kg) intraperitoneally to establish an iron overload mouse model and surgically induced osteoarthritis. The extent of OA and iron deposition were assessed using Micro-ct, Safranin-O/fast green staining, H&E staining, and Prussian Blue 10 weeks later. We administered primary chondrocytes with Ferric Ammonium Citrate (FAC) to evaluate the chondrocyte changes. Chondrocytes were identified in vitro by toluidine blue staining, and chondrocyte viability was evaluated by CCK-8. The rate of apoptosis was determined by Annexin V-FITC/PI assay. The mechanism of action of CAR was verified by adding the SIRT1 inhibitor EX527, and the expression of SIRT1 and MAPK signaling pathways was detected by Western blot. Iron overload also promoted chondrocyte apoptosis, a process that was reversed by CAR. In addition, CAR reduced NLRP3 inflammasome production via the SIRT1-MAPK pathway, and the SIRT1 inhibitor EX527 inhibited the treatment of OA by CAR.CAR inhibited cartilage degeneration induced by iron overload both in vivo and in vitro. Besides, our study showed that iron overload not only inhibited type II collagen expression but also induced MMP expression by catalyzing the generation of NLRP3 inflammasome. Our results suggest that CAR can treat KOA by promoting SIRT1 expression and inhibiting p38MAPK pathway expression to reduce the production of NLRP3 inflammasome vesicles.
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Inflamasomas , Osteoartritis , Animales , Ratones , Proteína con Dominio Pirina 3 de la Familia NLR , Especies Reactivas de Oxígeno , Sirtuina 1 , Osteoartritis/tratamiento farmacológico , Transducción de Señal , HierroRESUMEN
BACKGROUND: The traditional Chinese medicine Gusuibu, the rhizome of Rhizoma Drynariae, is used to treat rheumatism and fractures. Naringenin (NAR) is an active ingredient in Gusuibu and has significant anti-inflammatory and antioxidant effects. However, the role of naringenin in iron overload-induced osteoarthritis (IOOA) is unknown. HYPOTHESIS: NAR reduces cartilage damage in IOOA. METHODS: The effects of NAR on the viability of IOOA chondrocytes and the synthesis ability of type II collagen were evaluated using cell counting kit (CCK8) and toluidine blue assays. To determine the mechanism of action and characteristics of NAR, the intracellular iron ion content, apoptosis rate, and mitochondrial membrane potential (MMP) change, and malondialdehyde (MDA) levels, as well as the degree of reactive oxygen species (ROS) and lipid hydroperoxide (LPO) accumulation in the cells were detected in vitro and verified using western blotting and quantitative real-time PCR (qRT-PCR). To verify the role of NAR in vivo, IOOA mice were established using iron dextran and surgery-induced destabilised medial meniscus. Changes in the articular cartilage and subchondral bone were examined using Safranin O-fast Green staining (S-O), haematoxylin-eosin staining (H&E), and microcomputed tomography (µCT). RESULTS: In vitro, NAR attenuated the impairment of cell viability, apoptosis, and MMP caused by ferric ammonium citrate and interleukin-1ß co-culture, increased the levels of MDA, reduced the expression of matrix metallopeptidase (MMP)3, MMP13, and Bax, and restored the expression of type II collagen (Col II). NAR showed a slight iron accumulation-reducing effect. NAR alleviated the accumulation of ROS and LPO in IOOA chondrocytes and upregulated antioxidant genes nuclear factor E2-related factor 2 (NRF2) and haem oxygenase 1 (HO-1). When ML385, a specific NRF-2 inhibitor, was added, the protective effect of NAR was significantly inhibited. In vivo, NAR reduced synovitis and attenuated cartilage damage and subchondral bone proliferation in IOOA mice. CONCLUSIONS: NAR can reduce oxidative stress through the NRF2-HO-1 pathway, alleviate cartilage damage under iron overload, and has the potential to treat IOOA.
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Sobrecarga de Hierro , Osteoartritis , Animales , Antioxidantes , Apoptosis , Colágeno Tipo II , Flavanonas , Hierro , Ratones , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Especies Reactivas de Oxígeno , Transducción de Señal , Microtomografía por Rayos XRESUMEN
Drought stress remains one of the most detrimental environmental cues affecting plant growth and survival. In this work, the DNA methylome changes in mulberry leaves under drought stress (EG) and control (CK) and their impact on gene regulation were investigated by MethylRAD sequencing. The results show 138,464 (37.37%) and 56,241 (28.81%) methylation at the CG and CWG sites (W = A or T), respectively, in the mulberry genome between drought stress and control. The distribution of the methylome was prevalent in the intergenic, exonic, intronic and downstream regions of the mulberry plant genome. In addition, we discovered 170 DMGs (129 in CG sites and 41 in CWG sites) and 581 DMS (413 in CG sites and 168 in CWG sites). Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis indicates that phenylpropanoid biosynthesis, spliceosome, amino acid biosynthesis, carbon metabolism, RNA transport, plant hormone, signal transduction pathways, and quorum sensing play a crucial role in mulberry response to drought stress. Furthermore, the qRT-PCR analysis indicates that the selected 23 genes enriched in the KEGG pathways are differentially expressed, and 86.96% of the genes share downregulated methylation and 13.04% share upregulation methylation status, indicating the complex link between DNA methylation and gene regulation. This study serves as fundamentals in discovering the epigenomic status and the pathways that will significantly enhance mulberry breeding for adaptation to a wide range of environments.
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ETHNOPHARMACOLOGICAL RELEVANCE: XianLing GuBao Capsule (XLGB) is often used to treat osteoarthritis (OA), osteoporosis, fractures, and other musculoskeleton disorders. However, the molecular mechanism of XLGB for treating OA is still unclear. AIM OF THE STUDY: This study set out to uncover the molecular mechanism underlying the treatment of osteoarthritis with XLGB. MATERIALS AND METHODS: Disease genes were obtained from CTD, DisGeNET, and GeneCards databases, and XLGB drug targets were obtained from ETCM and target genes predicted by XLGB metabolic components reported in the literature. Then we used the Venn diagram viewer to extract disease and drug intersection genes as potential therapeutic genes for Protein-protein interaction (PPI), GO terminology, and KEGG pathway analysis. Subsequently, we performed qRT-PCR, Western blot and histological analysis to validate the therapeutic effect of XLGB against OA and its molecular mechanism. RESULTS: A total of 1039 OA genes and 949 XLGB target genes were collected, and finally 188 potential therapeutic target genes were obtained. PPI network analysis indicated that the main target genes for XLGB to treat OA include Akt1, Mapk3, Il-6, Il-1ß, Ptgs2, Mmp9, etc. The results of KEGG and GO enrichment analysis suggested that XLGB may treat OA by anti-inflammatory and reducing extracellular matrix degradation. In vitro, XLGB down-regulated the expressions of Mmp3, Mmp9, Mmp12, Mmp13, Cox-2, Il-6, increased the expression of Collagen II and Sox9. Mechanistically, XLGB inhibits the activation of PI3K/AKT/NF-κB and MAPK pathways. Moreover, the results of animal experiments indicated that XLGB reduced cartilage destruction, bone resorption, and synovitis in osteoarthritic rats. CONCLUSIONS: XLGB has a protective effect against OA by suppressing PI3K/AKT/NF-κB and MAPK signaling. Our study provides a theoretical basis for XLGB in the treatment of osteoarthritis.
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Osteoartritis , Proteínas Proto-Oncogénicas c-akt , Animales , Condrocitos , Biología Computacional , Interleucina-6 , Metaloproteinasa 9 de la Matriz , FN-kappa B/metabolismo , Osteoartritis/tratamiento farmacológico , Osteoartritis/genética , Fosfatidilinositol 3-Quinasas , RatasRESUMEN
Mulberry is an economically significant crop for the sericulture industry worldwide. Stresses such as drought exposure have a significant influence on plant survival. Because metabolome directly reflects plant physiological condition, performing a global metabolomic analysis is one technique to examine this influence. Using a liquid chromatography-mass spectrometry (LC-MS) technique based on an untargeted metabolomic approach, the effect of drought stress on mulberry Yu-711 metabolic balance was examined. For this objective, Yu-711 leaves were subjected to two weeks of drought stress treatment and control without drought stress. Numerous differentially accumulated metabolic components in response to drought stress treatment were revealed by multivariate and univariate statistical analysis. Drought stress treatment (EG) revealed a more differentiated metabolite response than the control (CK). We found that the levels of total lipids, galactolipids, and phospholipids (PC, PA, PE) were significantly altered, producing 48% of the total differentially expressed metabolites. Fatty acyls components were the most abundant lipids expressed and decreased considerably by 73.6%. On the other hand, the prenol lipids class of lipids increased in drought leaves. Other classes of metabolites, including polyphenols (flavonoids and cinnamic acid), organic acid (amino acids), carbohydrates, benzenoids, and organoheterocyclic, had a dynamic trend in response to the drought stress. However, their levels under drought stress decreased significantly compared to the control. These findings give an overview for the understanding of global plant metabolic changes in defense mechanisms by revealing the mulberry plant metabolic profile through differentially accumulated compounds.
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Preeclampsia causes gestational failure in a significant number of women annually. Insufficient trophoblast cell invasion plays an essential role in preeclampsia pathogenesis. Matrix-remodeling associated 5 (MXRA5) is a proteoglycan involved in adhesion and matrix remodeling. This study sought to explore the role of MXRA5 in trophoblast cell invasion. Preeclamptic villi were obtained for the delineation of MXRA5 expression. Specific MXRA5 siRNA and pcDNA3.1/MXRA5 were used to manipulate MXRA5 expression in HTR-8/SVneo. Cell viability was determined by MTT and apoptosis by flow cytometry. Cell invasion was evaluated using Matrigel invasion assay. MXRA5 expression was lower in preeclamptic villi and cytotrophoblasts. Silencing MXRA5 expression in HTR-8/SVneo decreased cell viability and invasion, which were augmented by MXRA5 overexpression. Furthermore, MXRA5 modulated N-cadherin, E-cadherin, MMP-2, and MMP-9 expression through p38 MAPK and ERK1/2 signaling transduction. In addition, the expression of MXRA5 was influenced by exogenous TNF-α but not by IFN-γ. Overexpression of MXRA5 attenuated HTR-8/SVneo apoptosis induced by TNF-α. MXRA5 is downregulated in preeclamptic cytotrophoblasts and can regulate trophoblast cell invasion via the MAPK pathway.
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Movimiento Celular , Sistema de Señalización de MAP Quinasas , Preeclampsia/patología , Proteoglicanos/metabolismo , Trofoblastos/patología , Adulto , Cadherinas/metabolismo , Movimiento Celular/efectos de los fármacos , Movimiento Celular/genética , Supervivencia Celular/efectos de los fármacos , Supervivencia Celular/genética , Vellosidades Coriónicas/efectos de los fármacos , Vellosidades Coriónicas/metabolismo , Vellosidades Coriónicas/patología , Femenino , Humanos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Preeclampsia/genética , Embarazo , Proteoglicanos/genética , Trofoblastos/efectos de los fármacos , Trofoblastos/metabolismo , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
The present study aimed to determine the genotype and age distribution of high-risk human papillomavirus (HR-HPV) and evaluate HPV-DNA in subjects with abnormal cervical cytology results by using crowd-based cervical cancer screening cytology data. The Thinprep liquid-based cytologic test (TCT) was performed from January 2013 to January 2014 in the permanent residents of Liaocheng (China) aged 21-65 years who were married or had sexual intercourse. The number of screened women totaled 20,017, among whom 937 had abnormal results, 785 of which were recalled. For subjects in the age range of 21-65 years, an HR-HPV typing test using the fluorescence hybridization method. Among the 785 cases with abnormal TCT findings, repeated testing identified atypical squamous cells of unknown significance/atypical glandular cells in 478, low-grade squamous intraepithelial lesions in 175, high squamous intraepithelial lesions in 127 and squamous cell carcinoma/adenocarcinoma in 5 cases. Among these types, infection rates of HR-HPV were 50.2, 77.1, 89.0 and 100%, respectively. Of the 785 cases with abnormal TCT results, 493 (62.8%) were HR-HPV-positive. A total of 16 types of HR-HPV were detected: HPV-16, -18, -31, -33, -35, -39, -45, -51-53, -56, -58, -59, -66, 68 and 73. Subjects infected with ≥2 types were defined as having a multi-type infection. The infection rate was high in the age groups of 26-30 and 51-55 years, accounting for 87.7% (71/81) and 79.7% (51/64), respectively, while it was lower in the >55 years group at 28.6% (14/54). The top five types of HR-HPV (stated in a decreasing order regarding positivity rate) were HPV16 (21.5%, 169/785), HPV52 (12.2%, 96/785), HPV58 (9.8%, 77/785), HPV33 (9.7%, 76/785) and HPV18 (7.5%, 59/785). Single-type infection was encountered in 45.0% (353/785) and multi-type infection in 17.8% (140/785), among which 98 cases had a two-type infection, 37 had a three-type infection, 2 had a four-type infection, 2 had a five-type infection and 1 case had a six-type infection. In the present study, differences in multi-type HR-HPV infection between groups with different TCT results were statistically significant. In conclusion, compared with CTC screening on its own, complementary HR-HPV testing is an effective method for screening for cervical cancer. The infection rate of HPV16, -52, -58, -33 and -18 was high among patients with cervical cytological abnormalities. Multi-type infection adds to the risk of malignancies. In Liaocheng, high-risk groups were aged 26-30 and 51-55. Attention should be paid during the screening and follow-up visits of these groups.
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Lactic acid bacteria have been identified to be effective in reducing cholesterol levels. Most of the mechanistic studies were focused on the bile salt deconjugation ability of bile salt hydrolase in lactic acid bacteria. However, the mechanism by which Lactobacillus decreases cholesterol levels has not been thoroughly studied in intact primate cells. 3-Hydroxy-3- methyl-glutaryl-coenzyme A reductase (HMGCR) is the vital enzyme in cholesterol synthesis. To confirm the effect of probiotic Lactobacillus strains on HMGCR level, in the present study, human hepatoma HepG2 cells were treated with Lactobacillus strains, and then the HMGCR level was illustrated by luciferase reporter assay and RT-PCR. The results showed that the level of HMGCR was suppressed after being treated with the live Lactobacillus strains. These works might set a foundation for the following study of the antihyperlipidemic effects of L. acidophilus, and contribute to the development of functional foods or drugs that benefit patients suffering from hyperlipidemia diseases.