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Mining causes severe damage to soil ecosystems. Vegetation restoration in abandoned mine areas is an inevitable requirement for sustainable development. Soil microbes, as the most active component of soil organic matter, play a crucial role in the transformation of carbon, nitrogen, phosphorus, and other elements. They are often used as indicators to assess the extent of vegetation restoration in ecologically fragile areas. However, the impacts of vegetation restoration on soil microbial community structure in mining areas at the global scale remains largely unknown. Based on 310 paired observations from 44 papers, we employed the meta-analysis approach to examine the influence of vegetation restoration on soil microbial abundance and biomass in mining area. The results indicated that vegetation restoration significantly promotes soil microbial biomass in mining areas. In comparison to bare soil, vegetation restoration leads to a significant 95.1% increase in soil microbial biomass carbon and a 87.8% increase in soil microbial biomass nitrogen. The abundance of soil bacteria, fungi, and actinomycetes are significantly increased by 1005.4%, 472.4%, and 177.7%, respectively. Among various vegetation restoration types, the exclusive plan-ting of trees exhibits the most pronounced promotion effect on soil microbial biomass and population, which results in a significant increase of 540.3% in soil fungi and 104.5% in actinomycetes, along with a respective enhancement of 110.3% and 106.4% in microbial biomass carbon and nitrogen. Model selection results revealed that soil satura-ted water content and vegetation restoration history contribute most significantly to the abundance of soil bacteria and fungi. Soil available nitrogen has the most significant impact on the abundance of actinomycetes and microbial biomass carbon, while soil available phosphorus emerges as a crucial factor affecting microbial biomass nitrogen. This research could contribute to understanding the relationship between vegetation restoration and the structure of soil microbial communities in mining areas, and providing scientific support for determining appropriate vegetation restoration types in mining areas.
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Ecossistema , Mineração , Microbiologia do Solo , China , Recuperação e Remediação Ambiental/métodos , Solo/química , Árvores/crescimento & desenvolvimento , Nitrogênio/análise , Bactérias/classificação , Bactérias/crescimento & desenvolvimento , Biomassa , Plantas , Conservação dos Recursos NaturaisRESUMO
Far-red absorbing allophycocyanins (APC), identified in cyanobacteria capable of FRL photoacclimation (FaRLiP) and low-light photoacclimation (LoLiP), absorb far-red light, functioning in energy transfer as light-harvesting proteins. We report an optimized method to obtain high purity far-red absorbing allophycocyanin B, AP-B2, of Chroococcidiopsis thermalis sp. PCC7203 by synthesis in Escherichia coli and an improved purification protocol. The crystal structure of the trimer, (PCB-ApcD5/PCB-ApcB2)3, has been resolved to 2.8 Å. The main difference to conventional APCs absorbing in the 650-670 nm range is a largely flat chromophore with the co-planarity extending, in particular, from rings BCD to ring A. This effectively extends the conjugation system of PCB and contributes to the super-red-shifted absorption of the α-subunit (λmax = 697 nm). On complexation with the ß-subunit, it is even further red-shifted (λmax, absorption = 707 nm, λmax, emission = 721 nm). The relevance of ring A for this shift is supported by mutagenesis data. A variant of the α-subunit, I123M, has been generated that shows an intense FR-band already in the absence of the ß-subunit, a possible model is discussed. Two additional mechanisms are known to red-shift the chromophore spectrum: lactam-lactim tautomerism and deprotonation of the chromophore that both mechanisms appear inconsistent with our data, leaving this question unresolved.
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The non-Hermitian skin effect (NHSE) on the non-Hermitian Haldane model with gain and loss on the honeycomb lattice with the outline of a triangle is discussed. The NHSE only occurs on the edge of the lattice, transforming the edge modes into the higher-order corner modes. The NHSE can also occur on a lattice with only loss, which can be treated as a lattice with gain and loss as well as a global loss added to it. When the saturated gain is added to the three corner sites of the dissipative lattice, a single-mode laser system is obtained. When any one site is stimulated initially, the system will reach a saturated state depending on the distribution of the corner modes, and the stable laser light is emitted by sites at the corners.
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Emerging evidence shows that KRAS-mutant colorectal cancer (CRC) depends on glutamine (Gln) for survival and progression, indicating that targeting Gln metabolism may be a promising therapeutic strategy for KRAS-mutant CRC. However, the precise mechanism by which Gln metabolism reprogramming promotes and coordinates KRAS-mutant CRC progression remains to be fully investigated. Here, we discovered that solute carrier 25 member 21 (SLC25A21) expression was downregulated in KRAS-mutant CRC, and that SLC25A21 downregulation was correlated with poor survival of KRAS-mutant CRC patients. SLC25A21 depletion selectively accelerated the growth, invasion, migration, and metastasis of KRAS-mutant CRC cells in vitro and in vivo, and inhibited Gln-derived α-ketoglutarate (α-KG) efflux from mitochondria, thereby potentiating Gln replenishment, accompanied by increased GTP availability for persistent KRAS activation in KRAS-mutant CRC. The restoration of SLC25A21 expression impaired the KRAS-mutation-mediated resistance to cetuximab in KRAS-mutant CRC. Moreover, the arrested α-KG efflux that occurred in response to SLC25A21 depletion inhibited the activity of α-KG-dependent DNA demethylases, resulting in a further decrease in SLC25A21 expression. Our studies demonstrate that SLC25A21 plays a significant role as a tumor suppressor in KRAS-mutant CRC by antagonizing Gln-dependent anaplerosis to limit GTP availability for KRAS activation, which suggests potential alternative therapeutic strategies for KRAS-mutant CRC.
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Neoplasias Colorretais , Glutamina , Humanos , Linhagem Celular Tumoral , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação para Baixo , Glutamina/metabolismo , Guanosina Trifosfato/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismoRESUMO
This research delineates the energy dissipation characteristics in coal crushing under impact loads, leveraging the capabilities of Separated Hopkinson Pressure Bar experimental system. A meticulous examination of both burst-prone and non-burst-prone coal samples during destruction processes was undertaken to decipher the dynamic compression mechanical attributes from perspectives of energy and fragmentatio's fractal dimensions. Burst-prone coal showcases a more pronounced escalation in fragmentation work in comparison to non-burst-prone samples, thereby illustrating a perceptible strain-rate dependent effect correlating with enhanced strain rates. Additionally, it was observed that incident, reflected, and transmitted energy trajectories for both sample categories follow an approximately linear ascendancy, albeit exhibiting diverse magnitudes. Burst-prone coal manifests a more rapid and focused energy growth compared to its non-burst-prone counterpart. When subjected to impact loads, a notable trend was discerned where the fragmentation's fractional dimension escalated persistently with both the incident energy and the crushing work, portraying a prominent growth effect. The insights garnered from this study pave the way for distinguishing between impacted and unimpacted coal samples using energy perspectives and fragmentation's fractal dimensions.
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Mounting evidence has demonstrated the considerable regulatory effects of long noncoding RNAs (lncRNAs) in the tumorigenesis and progression of various carcinomas. LncRNA Semaphorin 3B (SEMA3B) antisense RNA 1 (SEMA3B-AS1) has been found to be dysregulated in a few carcinomas recently. However, its potential function and mechanism in colorectal carcinoma (CRC) have not yet been examined. Here we show that SEMA3B-AS1 acts as a crucial regulator of CRC progression. We found that SEMA3B-AS1 expression was downregulated in CRC cell lines and tissues. Downregulation of SEMA3B-AS1 was significantly associated with poor survival in CRC patients. Overexpression of SEMA3B-AS1 reduced the cell growth and metastasis of CRC in vivo and in vitro. In addition, SEMA3B-AS1 promoted the expression of its sense-cognate gene SEMA3B, a member of the Semaphorin family (SEMAs), by recruiting EP300 to induce H3K9 acetylation at the SEMA3B promoter. Furthermore, we proved that SEMA3B-AS1 suppressed CRC angiogenesis by affecting the vascular endothelial growth factor signaling pathway activation which was regulated by the SEMA3B-NRP1 axis. Our work unravels a novel mechanism of SEMA3B-AS1 in the inhibition of CRC malignant progression and highlights its probability as a new promising diagnostic marker and therapeutic target for CRC interventions.
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A high-performance liquid chromatography-tandem mass spectrometry(LC-MS/MS) was developed for simultaneously determining the components(magnoflorine, jatrorrhizine, berberrubine, coptisine, berberine) of Jiaotai Pills and Fluoxetine in plasma of rats with chronic unpredictable mild stress(CUMS)-induced depression to investigate the pharmacokinetic herb-drug interaction of Jiaotai Pills and Fluoxetine in the rats. The six components showed good linear relationship within the corresponding concentration ranges, and the method showed high specificity, accuracy, precision, and stability. Their pharmacokinetic parameters were calculated by DAS 3.2.2, and the results showed that the in vivo metabolic processes of the six components accorded with the characteristics of non-compartmental model. When Jiaotai Pills and Fluoxetine were used together, the AUC_(0-t), AUC_(0-∞), C_(max), and C_(av) of magnoflorine all significantly increased(P<0.05), while the pharmacokinetic trend of berberrubine was opposite to that of magnoflorine, as manifested by the decrease in AUC_(0-t), AUC_(0-∞), T_(max), C_(max), and C_(av)(P<0.01, P<0.05). The pharmacokinetic characteristics of jatrorrhizine, coptisine, and berberine followed the trend of berberrubine. There was no significant difference in the pharmacokinetic characteristics of Fluoxetine in the single or combination groups. This study suggests that the enhanced antidepressant efficacy of Jiaotai Pills and Fluo-xetine may be attributed to the pharmacokinetic interaction.
Assuntos
Berberina , Fluoxetina , Animais , Cromatografia Líquida/métodos , Depressão/tratamento farmacológico , Medicamentos de Ervas Chinesas , Ratos , Espectrometria de Massas em Tandem/métodosRESUMO
OBJECTIVE: The purpose of this study was to explore the effect of dulaglutide on DHEA induced PCOS rats and its mechanism, to provide new drugs and research directions for clinical treatment of PCOS. METHODS: In this study, the PCOS model was established by giving female SD rats subcutaneous injection of DHEA for 21 consecutive days. After modeling, the treatment group was injected subcutaneously with three doses of dulaglutide for 3 weeks. The model group was injected with sterile ultrapure water, and the normal group did not get any intervention. The body weight changes of rats in each group were recorded from the first day when rats received the administration of dulaglutide. Three weeks later, the rats were fasted the night after the last treatment, determined fasting insulin and fasting glucose the next day. After the rats were anesthetized by chloral hydrate, more blood was collected from the heart of the rat. The serum insulin, testosterone and sex hormone binding globulin (SHBG) levels were detected by the enzyme-linked immunoassay method. After removing the adipose tissue, the obtained rat ovary tissue was used for subsequent experimental detection, using HE staining for morphology and follicular development analysis; qRT-PCR for the detection of 3ßHSD, CYP17α1, CYP19α1, and StAR gene expression in ovarian tissue; and western blotting analysis of CYP17α1, CYP19α1, StAR protein expression and insulin level to verify whether dulaglutide has a therapeutic effect on PCOS in rats. RESULTS: After treated with different concentrations of dulaglutide, we found that the body weight of rats in the treatment groups were reduced. Compared with the rats in PCOS group, the serum androgen level of rats in the treatment groups was significantly decreased, and the serum sex hormone binding protein content was significantly increased, and there was statistically significant difference between these groups and PCOS group. In terms of protein expression and gene regulation, the expression of 3ßHSD, CYP19α1 and StAR in the ovarian tissue of rats in treatment groups were decreased significantly after received the treatment of dulaglutide, and there was statistically significant difference between these groups and PCOS group. In addition, dulaglutide reduced the insulin content in the ovarian tissue of PCOS rats. CONCLUSION: Dulaglutide may reduce the hyperandrogenemia of PCOS rats by regulating the content of serum SHBG and the expression of 3ßHSD, CYP19α1, and StAR related genes and proteins, thereby inhibiting the excessive development of small follicles and the formation of cystic follicles in the ovaries of PCOS rats, thereby improving polycystic ovary in PCOS rats. In addition, dulaglutide may reduce the weight of PCOS rats, further reducing the level of high androgen in PCOS rats, and improving the morphology of their polycystic ovaries.
Assuntos
Peptídeos Semelhantes ao Glucagon/análogos & derivados , Fragmentos Fc das Imunoglobulinas/farmacologia , Ovário/efeitos dos fármacos , Síndrome do Ovário Policístico/tratamento farmacológico , Proteínas Recombinantes de Fusão/farmacologia , Animais , Peso Corporal/efeitos dos fármacos , Desidroepiandrosterona/toxicidade , Modelos Animais de Doenças , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Peptídeos Semelhantes ao Glucagon/farmacologia , Resistência à Insulina , Ovário/fisiopatologia , Ovulação/efeitos dos fármacos , Fosfoproteínas/genética , Fosfoproteínas/metabolismo , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/fisiopatologia , Ratos Sprague-Dawley , Globulina de Ligação a Hormônio Sexual/análise , Esteroide 17-alfa-Hidroxilase/genética , Esteroide 17-alfa-Hidroxilase/metabolismo , Testosterona/sangueRESUMO
OBJECTIVE: The purpose of the experiments in this study was to explore the effect of exenatide on intrauterine adhesions (IUAs) and to elucidate its mechanism to provide new ideas for the clinical treatment of IUAs. METHODS: In this study, an animal model of IUAs was established by double stimulation using mechanical curettage and inflammation. After modeling, the treatment group was injected subcutaneously with three doses of exenatide for two weeks. The model group was injected with sterile ultrapure water, and the sham operation group was treated the same as the normal group, except for the observation of abdominal wound changes. Two weeks later, all mice were sacrificed by cervical dysfunction. The obtained mouse uterine tissue was used for subsequent experimental detection, using HE and Masson staining for histomorphological and pathological analysis; qRT-PCR for the detection of TGF-ß1, α-SMA, and MMP-9 gene expression in uterine tissue; and western blotting analysis of TGF-ß1, α-SMA, and collagen 1 protein expression to verify whether exenatide has a therapeutic effect on IUAs in mice. RESULTS: In the high-dose exenatide treatment group, the endometrial glands significantly increased in size, and the deposition area of collagen fibers in the endometrial tissue was significantly reduced. We observed that the mRNA expression of TGF-ß1 and α-SMA in the endometrial tissue of IUAs mice in this group was significantly reduced, while the expression of MMP-9 was significantly increased. In addition, we found that the protein expression of TGF-ß1, α-SMA, and collagen 1 remarkably decreased after treatment with exenatide. CONCLUSION: Exenatide may reduce the deposition of collagen fibers in the uterus of IUAs mice and promote the proliferation of endometrial glands in mice.
Assuntos
Actinas/genética , Exenatida/farmacologia , Peptídeo 1 Semelhante ao Glucagon/genética , Aderências Teciduais/tratamento farmacológico , Fator de Crescimento Transformador beta1/genética , Animais , Colágeno Tipo I/genética , Modelos Animais de Doenças , Endométrio/efeitos dos fármacos , Endométrio/patologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Metaloproteinase 9 da Matriz/genética , Camundongos , Aderências Teciduais/genética , Aderências Teciduais/patologia , Útero/efeitos dos fármacos , Útero/patologiaRESUMO
The present study investigated the effects and mechanisms of Jiaotai Pills on depressed mice induced by chronic unpredictable mild stress(CUMS). The CUMS-induced depression model mice were established and the depression behaviors of mice were evaluated by sucrose preference test, open field test, tail suspension test, and forced swimming test. Molecular docking was employed to simulate the interaction of six main active ingredients in Jiaotai Pills with SIRT1. Immunohistochemical staining was used to detect the level of SIRT1 in the hippocampus of mice. Western blot was used to detect the protein expression levels of SIRT1, p-NF-κB p65, NF-κB p65, and FoxO1 in the hippocampus of mice. Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the levels of interleukin(IL)-1ß, IL-6, tumor necrosis factor-α(TNF-α), and brain-derived neurotrophic factor(BDNF) in the hippocampus and serum of mice. Biochemical kits were used to detect superoxide dismutase(SOD) activity and malondialdehyde(MDA) and glutathione(GSH) levels in the hippocampus and serum of mice. Liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to detect the levels of dopamine(DA), 5-hydroxytryptamine(5-HT), and norepinephrine(NE) in the hippocampus and serum of mice. The results showed that the sucrose preference rate, movement distance, and the number of crossing centers were reduced in the model group(P<0.01), and the tail suspension time and swimming immobility time were increased(P<0.01). Molecular docking results indicated good binding of six main active ingredients in Jiaotai Pills to SIRT1. In the hippocampus, the expression level of SIRT1 was reduced(P<0.01), and the levels of p-NF-κB p65/NF-κB p65 and FoxO1 were increased(P<0.01). In the hippocampus and serum, the levels of IL-1ß, IL-6, TNF-α, and MDA were increased(P<0.01), and the activity of SOD and the levels of GSH, DA, 5-HT, NE, and BDNF were reduced(P<0.01). The treatment with high-dose Jiaotai Pills increased the sucrose preference rate, movement distance, and the number of crossing centers(P<0.05), reduced tail suspension time and swimming immobility time(P<0.01), elevated hippocampal SIRT1 expression level(P<0.01), decreased hippocampal and serum IL-1ß, IL-6, TNF-α, and MDA levels(P<0.01), potentiated SOD activity, and up-regulated GSH, DA, 5-HT, NE, and BDNF levels in the hippocampus and serum(P<0.05, P<0.01) in model mice. In conclusion, the results showed that Jiaotai Pills could improve the depression behaviors of model mice with CUMS-induced depression, and the underlying mechanism was related to the up-regulation of SIRT1 in the hippocampus of mice to exert anti-inflammatory and anti-oxidative stress effects.
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Antidepressivos , Depressão , Animais , Comportamento Animal , Cromatografia Líquida , Depressão/tratamento farmacológico , Depressão/etiologia , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas , Hipocampo , Camundongos , Simulação de Acoplamento Molecular , Sirtuína 1/genética , Estresse Psicológico , Espectrometria de Massas em TandemRESUMO
Ovarian cancer (OC) is one of the deadliest gynecological malignancy. Epithelial ovarian cancer (EOC) is its most common form. OC has both, a poor prognosis and a high mortality rate due to the difficulties of early diagnosis, limitation of current treatment and resistance to chemotherapy. Extracellular vesicles (EVs) is a heterogeneous group of cell-derived submicron vesicles, which can be detected in body fluids, and it can be classified into three main types including exosomes, micro-vesicles, and apoptotic bodies. Cancer cells can produce more EVs than healthy cells. Moreover, the contents of these EVs have been found distinctive from each other. It has been considered that EVs shedding from tumor cells may be implicated in clinical applications, such as a tool for tumor diagnosis, prognosis and potential treatment of certain cancers. In this review, we provide a brief description of EVs. in diagnosis, prognosis, treatment, and drug-resistantance of OC. Cancer-related EVs show powerful influences on tumors by various biological mechanisms. However, the contents mentioned above remain in the laboratory stage and there is a lack of large-scale clinical trials, and the maturity of the purification and detection methods is a constraint. In addition, amplification of oncogenes on ecDNA is remarkably prevalent in cancer. It may be possible that ecDNA can be encapsulated in EVs and thus detected by us. In summary, much more research on EVs needs to be performed to reveal breakthroughs in OC and to accelerate the process of its application in clinic.
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Antineoplásicos/farmacologia , Vesículas Extracelulares/patologia , Neoplasias Ovarianas , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , PrognósticoRESUMO
A novel exopolysaccharide (EPS) from Paenibacillus polymyxa PYQ1 was extracted, well purified and characterized. This EPS was homogeneous glucomannan-type polysaccharide with the average molecular weight of 4.38 × 106 Da. Structural characterization indicated that the monosaccharides of EPS were pyranoses connected by ß-glycosidic linkages. Furthermore, our results showed the protective benefits of EPS against UVC induced cytotoxicity in HaCaT cells through scavenging excessive reactive oxygen species, mitigating the decrease of mitochondrial membrane potential, improving catalase activity and maintaining membrane integrity. Taken together, this study qualified EPS from P. polymyxa PYQ1 was a promising natural polymer which worth further investigation as a skin-care agent.
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Citoproteção/efeitos dos fármacos , Paenibacillus polymyxa/metabolismo , Polissacarídeos Bacterianos/isolamento & purificação , Polissacarídeos Bacterianos/farmacologia , Raios Ultravioleta/efeitos adversos , Catalase/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/efeitos da radiação , Peso Molecular , Monossacarídeos/análise , Polissacarídeos Bacterianos/biossíntese , Polissacarídeos Bacterianos/química , Espécies Reativas de Oxigênio/metabolismoRESUMO
CD44 antigen (CD44) is a transmembrane protein found in cell adhesion molecules and is involved in the regulation of various physiological processes in cells. It was hypothesized that CD44 directly affected the chondrogenic differentiation of human amniotic mesenchymal stem cells (hAMSCs). In the present study, the expression of chondrocyteassociated factors was detected in the absence and presence of the antibody blocker antiCD44 antibody during the chondrogenic differentiation of hAMSCs. Following inhibition of CD44 expression, the transcriptional levels of chondrocyteassociated genes SRYbox transcription factor 9, aggrecan and collagen type II α 1 chain, as well as the production of chondrocyte markers type II collagen and aggrecan were significantly decreased in hAMSCs. Further investigation indicated that there was no significant change in total ERK1/2 expression following inhibition of CD44 expression; however, phosphorylated (p)ERK1/2 expression was decreased. The expression of pSmad2/3 was also upregulated following CD44 inhibition. These data indicated that CD44 may affect the differentiation of hAMSCs into chondrocytes by regulating the Smad2/3 and ERK1/2 signaling pathway.
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Âmnio/metabolismo , Diferenciação Celular/efeitos dos fármacos , Condrócitos/metabolismo , Receptores de Hialuronatos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Transdução de Sinais/efeitos dos fármacos , Agrecanas/metabolismo , Condrogênese/efeitos dos fármacos , Colágeno Tipo II/metabolismo , Humanos , Receptores de Hialuronatos/genética , Sistema de Sinalização das MAP Quinases , Fosforilação , Proteína Smad2/metabolismo , Proteína Smad3/metabolismoRESUMO
Osteogenic inducers play central roles in effective stem cell-based treatment of bone defects/losses. However, the current routine osteogenic inducer is a cocktail comprising three components that must be improved due to low induction efficiency and side effects. Therefore, there is an urgent need to develop safer and more effective osteoinducers. Herein, we demonstrated the osteogenic effect of Ganoderal A (GD-A), a tetracyclic triterpenoid compound from Ganoderma lucidum. GD-A showed no cytotoxicity toward human amniotic mesenchymal stem cells (hAMSCs) at doses of 0.001-10 µM; furthermore, 0.01 µM GD-A significantly induced the generation of osteoblast-specific markers, such as alkaline phosphatase, and calcium deposition in hAMSCs. At molecular levels, GD-A promoted the expression of multiple osteoblast differentiation markers, such as RUNX2, OSX, OPN, ALP, OCN, and COL1α1. Both Wnt/ß-catenin and BMP/SMAD signaling were shown as active during hAMSC osteodifferentiation. Furthermore, specific blocking of both signals by KYA1797K and SB431542 significantly inhibited alkaline phosphatase secretion and RUNX2 and ALP expression when used alone or in combination. Meanwhile, both signals were also blocked. These findings suggest that GD-A induces hAMSC differentiation into osteoblasts through signaling cross-talk between Wnt/ß-catenin and BMP/SMAD. Taken together, GD-A is a safe, effective, and novel osteoinducer and might be used for stem cell-based therapy for bone defects/losses.
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Âmnio/citologia , Proteínas Morfogenéticas Ósseas/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Osteogênese/efeitos dos fármacos , Proteínas Smad/metabolismo , Triterpenos/farmacologia , Via de Sinalização Wnt , Diferenciação Celular/genética , Forma Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Modelos Biológicos , Osteogênese/genética , Fenótipo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Triterpenos/química , Via de Sinalização Wnt/efeitos dos fármacos , Via de Sinalização Wnt/genéticaRESUMO
Interleukin (IL)-1ß and tumor necrosis factor (TNF)-α, in particular, control the degeneration of articular cartilage, making them prime targets for osteoarthritis (OA) therapeutic strategies. Advanced oxidation protein products (AOPPs) are prevalent in numerous diseases. Our previous work demonstrates that intra-articular injections of AOPPs accelerate regression of cartilage in OA models. Whether AOPPs exist in the course of OA and their effects on TNF-α and IL-1ß expression in chondrocytes are still unclear. This study confirmed that AOPPs levels in human synovial fluid were positively associated with severity of OA. We also found AOPPs deposition in articular cartilage in anterior cruciate ligament transection (ACLT) induced rodent OA models. AOPPs increased expression of TNF-α and IL-1ß in chondrocytes in vitro, which was inhibited by pre-treatment with SB202190 (p38-MAPK inhibitor) or apocynin (NADPH oxidase inhibitor) or NOX4 knockdown by siRNAs. Subsequently, we further verified in vivo that exogenous injection of AOPPs in OA mice up-regulated expression of TNF-α and IL-1ß in cartilage, which was blocked by treatment with apocynin. In parallel, apocynin attenuated articular cartilage degeneration resulting in substantially lower OARSI scores. Specifically, apocynin reduced NOX4, p-P38, TNF-α and IL-1ß and increased collagen II and glycosaminoglycan (GAG). This study demonstrated that AOPPs increased expression of TNF-α and IL-1ß in chondrocytes via the NADPH oxidase4-dependent and p38-MAPK mediated pathway, and accelerated cartilage degeneration in OA progression. These findings suggest an endogenous pathogenic role of AOPPs in OA progression. Targeting AOPPs-triggered cellular mechanisms might be a promising therapeutic option for patients with OA.
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Produtos da Oxidação Avançada de Proteínas/metabolismo , Condrócitos/citologia , Interleucina-1beta/metabolismo , NADPH Oxidase 4/metabolismo , Osteoartrite do Joelho/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Adulto , Produtos da Oxidação Avançada de Proteínas/efeitos adversos , Idoso , Animais , Células Cultivadas , Condrócitos/metabolismo , Modelos Animais de Doenças , Progressão da Doença , Feminino , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Osteoartrite do Joelho/induzido quimicamente , Índice de Gravidade de Doença , Líquido Sinovial/metabolismo , Regulação para CimaRESUMO
BACKGROUND: Nowadays, people diagnosed sepsis may develop acute kidney injury (AKI), resulting heavy burden of health care. Recombinant human erythroprotein (rhEPO) has been suggested to have multifunction and may be used in the prevention or treatment of AKI, and its underlying mechanism remains largely unknown. METHODS: In our study, cell model induced by LPS-activated cell apoptosis in vitro and AKI animal model caused by lipopolysaccharide (LPS) injection in vivo. MTT assay and Flow Cytometry were conducted to analyze cell viability and apoptosis, respectively. Western bot was used to analyze expressions of apoptosis and autophagy associated proteins, and effects on AMPK/SIRT1 pathway. RESULTS: Our results suggested that rhEPO inhibited LPS-induced cell apoptosis in HK-2 and HEK-293. Moreover, we found that rhEPO activated autophagy to prevented cell apoptosis, changing the expression level of autophagy associated proteins such as LC3-I/LC3-II and P62, and AMPK/SIRT1 pathway was involved in its regulation. Additionally, both EX527 (SIRT1 inhibitor) and Compound C (AMPK inhibitor) blocked the autophagy effects caused by rhEPO and thus reversed the anti-apoptotic effects of rhEPO. Furthermore, our data demonstrated that rhEPO inhibited LPS-induced kidney tubular injury and decreased the expression level of apoptotic proteins by altering the expression level of autophagy related proteins and AMPK/SIRT1 pathway related proteins in vitro. CONCLUSION: Collectively, rhEPO suppressed LPS-induced cell apoptosis via AMPK/SIRT1 pathway mediated autophagy, and modulating their levels may serve as potential way in preventing AKI.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Injúria Renal Aguda/patologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Eritropoetina/farmacologia , Proteínas Recombinantes/farmacologia , Sepse/patologia , Sirtuína 1/metabolismo , Injúria Renal Aguda/complicações , Animais , Células HEK293 , Humanos , Lipopolissacarídeos , Masculino , Ratos Wistar , Sepse/complicações , Transdução de Sinais/efeitos dos fármacosRESUMO
OBJECTIVE: Lung cancer is the most prevalent cancer in the world, and lung adenocarcinoma is the most common lung cancer subtype. Identification and determination of relevant prognostic markers are the key steps to personalized cancer management. METHODS: We collected the gene expression profiles from 265 tumor tissues of stage I patients from The Cancer Genome Atlas (TCGA) databases. Using Cox regression model, we evaluated the association between gene expression and the overall survival time of patients adjusting for gender and age at initial pathologic diagnosis. RESULTS: Age at initial pathologic diagnosis was identified to be associated with the survival, while gender was not. We identified that 15 genes were significantly associated with overall survival time of patients (FDR < 0.1). The 15-mRNA signature- based risk score was helpful to distinguish patients of high-risk group from patients of low-risk group. CONCLUSION: Our findings reveal novel genes associated with lung adenocarcinoma survival and extend our understanding of how gene expression contributes to lung adenocarcinoma survival. These results are helpful for the prediction of the prognosis and personalized cancer management.
Assuntos
Adenocarcinoma de Pulmão/genética , Perfilação da Expressão Gênica , Neoplasias Pulmonares/genética , Adenocarcinoma de Pulmão/patologia , Humanos , Neoplasias Pulmonares/patologia , PrognósticoRESUMO
BACKGROUND: Long noncoding RNAs (lncRNAs) have been indicated to play critical roles in cancer development and progression. LncRNA HOXD cluster antisense RNA1 (HOXD-AS1) has recently been found to be dysregulated in several cancers. However, the expression levels, cellular localization, precise function and mechanism of HOXD-AS1 in colorectal carcinoma (CRC) are largely unknown. METHODS: Real-time PCR and in situ hybridization were used to detect the expression of HOXD-AS1 in CRC tissue samples and cell lines. Gain- and loss-of-function experiments were performed to investigate the biological roles of HOXD-AS1 in CRC cell line. RNA pull down, RNA immunoprecipitation and chromatin immunoprecipitation assays were conducted to investigate the mechanisms underlying the functions of HOXD-AS1 in CRC. RESULTS: We observed that HOXD-AS1 was located in the nucleus of CRC cells and that nuclear HOXD-AS1 was downregulated in most CRC specimens and cell lines. Lower levels of nuclear HOXD-AS1 expression were associated with poor outcomes of CRC patients. HOXD-AS1 downregulation enhanced proliferation and migration of CRC cells in vitro and facilitated CRC tumourigenesis and metastasis in vivo. Mechanistic investigations revealed that HOXD-AS1 could suppress HOXD3 transcription by recruiting PRC2 to induce the accumulation of the repressive marker H3K27me3 at the HOXD3 promoter. Subsequently, HOXD3, as a transcriptional activator, promoted Integrin ß3 transcription, thereby activating the MAPK/AKT signalling pathways. CONCLUSION: Our results reveal a previously unrecognized HOXD-AS1-HOXD3-Integrin ß3 regulatory axis involving in epigenetic and transcriptional regulation constitutes to CRC carcinogenesis and progression.
Assuntos
Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Integrina beta3/genética , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Proto-Oncogênicas c-akt/genética , RNA Longo não Codificante/genética , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Feminino , Células HCT116 , Proteínas de Homeodomínio/metabolismo , Humanos , Integrina beta3/metabolismo , Metástase Linfática , Masculino , Camundongos , Pessoa de Meia-Idade , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Estadiamento de Neoplasias , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Análise de Sobrevida , Fatores de Transcrição , Ativação Transcricional , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Accumulating evidence suggests that long noncoding RNA (lncRNA) plays important regulatory roles in cancer biology. However, the involvement of lncRNA in colorectal carcinoma progression remains largely unknown, especially in colorectal carcinoma metastasis. In this study, we investigated the changes in lncRNA expression in colorectal carcinoma and identified a new lncRNA, the antisense transcript of SATB2 (SATB2-AS1), as a key regulator of colorectal carcinoma progression. SATB2-AS1 was frequently downregulated in colorectal carcinoma cells and tissues, and patients whose tumors expressed SATB2-AS1 at low levels had a shorter overall survival and poorer prognosis. Downregulation of SATB2-AS1 significantly promoted cell proliferation, migration, and invasion in vitro and in vivo, demonstrating that it acts as a tumor suppressor in colorectal carcinoma. SATB2-AS1 suppressed colorectal carcinoma progression by serving as a scaffold to recruit p300, whose acetylation of H3K27 and H3K9 at the SATB2 promoter upregulated expression of SATB2, a suppressor of colorectal carcinoma growth and metastasis. SATB2 subsequently recruited HDAC1 to the Snail promoter, repressing Snail transcription and inhibiting epithelial-to-mesenchymal transition. Taken together, these data reveal SATB2-AS1 as a novel regulator of the SATB2-Snail axis whose loss facilitates progression of colorectal carcinoma. SIGNIFICANCE: These data show that the lncRNA SATB2-AS1 mediates epigenetic regulation of SATB2 and Snail expression to suppress colorectal cancer progression.See related commentary by Li, p. 3536.
Assuntos
Neoplasias Colorretais/genética , Proteínas de Ligação à Região de Interação com a Matriz , RNA Longo não Codificante , Linhagem Celular Tumoral , Movimento Celular , Epigênese Genética , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Fatores de TranscriçãoRESUMO
PURPOSE: To study the clinical effect of Vitallium removable partial denture (RPD) with dual major connector (DMC) in rehabilitation of Kennedy â and â ¡ dentition defect. METHODS: A total of 30 patients with Kennedy â and â ¡ dentition defect fitting to the inclusion criteria were selected and restored with Vitallium RPD with DMC. Patients were re-called at the 6th and 12th month for clinical follow-up examination of gingival index (GI), abutment teeth mobility (TM), X-ray imaging, probing depth (PD) and satisfaction surveys. Then the differences of each index were analyzed with SPSS 18.0 software package. RESULTS: GI, TM and X-ray features of free-end abutment teeth in 30 clinical cases had no obvious changes either at the early 6-month or at the later 12-month, and PD had no significant difference, either (F=0.0046, P=0.9954). Satisfaction surveys showed high satisfaction, especially in the respects of aesthetics (93.33ï¼ ) and comfort (86.67ï¼ ). CONCLUSIONS: From this study, it is concluded that Vitallium RPD with DMC have certain protective effect on the free-end abutment teeth, especially with the poor periodontal condition. It also shows high rate of patients' satisfaction. Therefore, it can be used as one of the common designs of RPD in cases of free-end dentition defect.