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The concept of sepsis has recently evolved from one of a 'systemic inflammatory response syndrome caused by infection' to a 'severe, potentially fatal organic dysfunction caused by an inadequate or imbalanced host response to infection'. Organ dysfunction is closely related to sepsis. Multiple organ dysfunction syndrome (MODS) is the most serious outcome of sepsis, often leading to a poor prognosis. However, specific drugs for sepsis and MODS caused by sepsis remain undetermined, and the fatality rate is relatively high. Under the guidance of modern medicine, traditional Chinese medicine (TCM) has gained a wealth of experience in the prevention and treatment of sepsis and plays a key role via the effects of its numerous components, pathways and targets. This study used 'Sepsis', 'Organ dysfunction' and 'Traditional Chinese medicine' as strategies for searching the databases of Chinese National Knowledge Infrastructure, Wanfang, PubMed and The Web of Science. This paper presents an overview of the current status of TCM component formulations for preventing and treating sepsis with MODS to provide a theoretical basis for clinical treatment and drug development.
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Litter size is an important indicator to measure the reproductive performance of goats, which is affected by the reproductive function of animals. The hypothalamus, as the regulatory center of the endocrine system, plays an important role in the reproduction of female animals. Here, we performed high-throughput RNA sequencing using hypothalamic tissue from high-fecundity and low-fecundity Leizhou goats to explore critical functional genes associated with litter size. Differentially expressed mRNA, lncRNA, and circRNAs were screened using DESeq and were enriched, and then analyzed by Gene Ontology and Kyoto Encyclopedia of Gene and Genome. Results showed that some of these differentially expressed mRNAs could be enriched in reproductive processes, jak-STAT, prolactin signaling pathway, and other signaling pathways related to reproduction, such as SOCS3. Furthermore, the central proteins POSTN, MFAP5, and DCN from protein-protein interaction may regulate animal reproductive activity by affecting cell proliferation and apoptosis. lncRNA MSTRG.33887.2 as well as circRNAs chicirc_098002, chicirc_072583, and chicirc_053531 may be able to influence animal reproduction by participating in folate metabolism and energy metabolism homeostasis through their respective target genes. Our results expand the molecular mechanism of hypothalamic regulation on animal reproduction.
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RNA Circular , RNA Longo não Codificante , Animais , Gravidez , Feminino , RNA Mensageiro/genética , RNA Longo não Codificante/genética , Perfilação da Expressão Gênica , Cabras/genética , Tamanho da Ninhada de Vivíparos/genética , HipotálamoRESUMO
Cardiac hypertrophy is a key structural change in diabetic cardiomyopathy, which mechanism is unknown. 14,15-Epoxyeicosatrienoic acid (14,15-EET) generated from arachidonic acid by CYP2J2 has beneficial effects in metabolic syndrome, which also plays vital roles in inflammatory response. Peroxisome proliferator activated receptors (PPARs) are members of the nuclear receptor superfamily and have three subtypes of α, ß (or δ) and γ. Studies have found that 14,15-EET can perform various biological functions by activating PPARs, but its role in diabetic cardiac hypertrophy is unknown. This study aimed to investigate the role of 14,15-EET-PPARs signaling pathway in the development of diabetic cardiac hypertrophy. Diabetic cardiac hypertrophy was developed by high-fat diet feeding combined with streptozotocin (40 mg/kg/d for 5 days, i.p.) in mice and was induced by glucose at 25.5 mmol/L (high glucose, HG) in H9c2 cells. The decreased level of 14,15-EET and the down-regulated expression of PPARα, PPARß and PPARγ were found following diabetic cardiac hypertrophy in mice. Similarly, both the level of 14,15-EET and the PPARs expression were also reduced in HG-induced hypertrophic cardiomyocytes. Supplementation with 14,15-EET improved the cardiomyocyte hypertrophy and up-regulated PPARs expression, which were nullified by 14,15-EEZE, a 14,15-EET antagonist. Taken together, we conclude that the decreased 14,15-EET is involved in the development of diabetic cardiac hypertrophy through the down-regulation of PPARs.
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Diabetes Mellitus , Cardiomiopatias Diabéticas , Ácido 8,11,14-Eicosatrienoico/análogos & derivados , Animais , Cardiomegalia/metabolismo , Diabetes Mellitus/metabolismo , Cardiomiopatias Diabéticas/metabolismo , Glucose/metabolismo , Camundongos , Miócitos Cardíacos/metabolismo , PPAR gama/metabolismoRESUMO
BACKGROUND: Inflammatory osteolysis, a major complication of total joint replacement surgery, can cause prosthesis failure and necessitate revision surgery. Macrophages are key effector immune cells in inflammatory responses, but excessive M1-polarization of dysfunctional macrophages leads to the secretion of proinflammatory cytokines and severe loss of bone tissue. Here, we report the development of macrophage-biomimetic porous SiO2-coated ultrasmall Se particles (porous Se@SiO2 nanospheres) to manage inflammatory osteolysis. RESULTS: Macrophage membrane-coated porous Se@SiO2 nanospheres(M-Se@SiO2) attenuated lipopolysaccharide (LPS)-induced inflammatory osteolysis via a dual-immunomodulatory effect. As macrophage membrane decoys, these nanoparticles reduced endotoxin levels and neutralized proinflammatory cytokines. Moreover, the release of Se could induce macrophage polarization toward the anti-inflammatory M2-phenotype. These effects were mediated via the inhibition of p65, p38, and extracellular signal-regulated kinase (ERK) signaling. Additionally, the immune environment created by M-Se@SiO2 reduced the inhibition of osteogenic differentiation caused by proinflammation cytokines, as confirmed through in vitro and in vivo experiments. CONCLUSION: Our findings suggest that M-Se@SiO2 have an immunomodulatory role in LPS-induced inflammation and bone remodeling, which demonstrates that M-Se@SiO2 are a promising engineered nanoplatform for the treatment of osteolysis occurring after arthroplasty.
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Materiais Biomiméticos , Fatores Imunológicos , Macrófagos , Nanocompostos/química , Osteólise/metabolismo , Animais , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Citocinas/metabolismo , Modelos Animais de Doenças , Fatores Imunológicos/química , Fatores Imunológicos/farmacologia , Imunoterapia , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Porosidade , Células RAW 264.7 , Selênio/química , Selênio/farmacologia , Dióxido de Silício/química , Dióxido de Silício/farmacologiaRESUMO
Previous studies of brain structural abnormalities in attention-deficit/hyperactivity disorder (ADHD) samples scarcely excluded comorbidity or analyzed them in subtypes. This study aimed to identify neuroanatomical alterations related to diagnosis and subtype of ADHD participants without comorbidity. In our cross-sectional analysis, we used T1-weighted structural MRI images of individuals from the ADHD-200 database. After strict exclusion, 121 age-matched children with uncomorbid ADHD (54 with ADHD-inattentive [iADHD] and 67 with ADHD-combined [cADHD]) and 265 typically developing control subjects (TDC) were included in current investigation. The established method of voxel-based morphometry (VBM8) was used to assess global brain volume and regional grey matter volume (GM). Our results showed that the ADHD patients had more regional GM in the bilateral thalamus relative to the controls. Post hoc analysis revealed that regional GM increase only linked to the iADHD subtype in the right thalamus and precentral gyrus. Besides, the right thalamus volume was positively related to inattentive severity in the iADHD. There were no group differences in global volume. Our results provide preliminary evidence that cerebral structural alterations are tied to uncomorbid ADHD subjects and predominantly attribute to iADHD subtype. Furthermore, the volume of the right thalamus may be relevant to inattentive symptoms in iADHD possibly related to a lack of inhibition of irrelevant sensory input.
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Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico por imagem , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Criança , Comorbidade , Estudos Transversais , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Tálamo/diagnóstico por imagemRESUMO
Magnetic-based theranostics feature a high efficiency, excellent tissue penetration, and minimal damage to normal tissues, are noninvasive, and are widely used in the diagnosis and therapy of clinical diseases. Herein, a conceptually novel magnetostrictive-piezoelectric nanocatalytic medicine (MPE-NCM) for tumor therapy is proposed by initiating an intratumoral magneto-driven and piezoelectric-catalyzed reaction using core-shell structured CoFe2O4-BiFeO3 magnetostrictive-piezoelectric nanoparticles (CFO-BFO NPs) under an alternating magnetic field. The CFO-BFO NPs catalyze the generation of cytotoxic reactive oxygen species (ROS): superoxide radicals (â¢O2-) and hydroxyl radicals (â¢OH). The simulation calculation demonstrates the highly controllable electric polarization, facilitating the above catalytic reactions under the magnetic stimulation. Both a detailed cell-level assessment and the tumor xenograft evaluation evidence the significant tumor eradication efficacy of MPE-NCM. This study proposes an original and novel magneto-responsive nanocatalytic modality for cancer therapy, which displays promising prospects for the future clinic translation owing to its excellent catalytic dynamic responsiveness, high therapeutic efficacy, and biosafety in vivo.
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Peróxido de Hidrogênio , Fototerapia , Catálise , Linhagem Celular Tumoral , Radical HidroxilaRESUMO
Incurable bacterial infections, impenetrable microbial biofilm, and irreversible antibiotic resistance are among the most dangerous threats for humans. With few effective strategies available in antimicrobial and antibiofilm development, innovative methodologies inspired by the advances in other fields such as nanomedicine are becoming more and more attractive to realize innovative antibacterial agents. Herein, a 2D niobium carbide (Nb2C) MXene titanium plate (Nb2C@TP)-based clinical implant with practical multimodal anti-infection functions was developed. Such emerging modes are capable of destroying biofilms for direct bacteria elimination through down-regulating bacterial energy metabolism pathways, suppressing biofilm formation, and enhancing as-formed biofilm detachment via an activating accessory gene regulator. Another intriguing feature of this nanomedicine is the sensitization ability toward bacteria via photothermal transduction, which reduces the temperature necessary for bacteria eradication and mitigates possible normal tissue damage. Moreover, the Nb2C@TP medical implant is able to alleviate proinflammatory responses by scavenging excessive reactive oxygen species in infectious microenvironments, benefiting angiogenesis and tissue remodeling.
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Infecções Bacterianas , Nióbio , Antibacterianos/farmacologia , Biofilmes , HumanosRESUMO
Triple-negative breast cancer (TNBC) is highly aggressive and insensitive to conventional targeted therapies, resulting in poor therapeutic outcomes. Recent studies have shown that abnormal iron metabolism is observed in TNBC, suggesting an opportunity for TNBC treatment via the iron-dependent Fenton reaction. Nevertheless, the efficiency of current Fenton reagents is largely restricted by the lack of specificity and low intracellular H2 O2 level of cancer cells. Herein, core-shell-satellite nanomaces (Au @ MSN@IONP) are fabricated, as near-infrared (NIR) light-triggered self-fueling Fenton reagents for the amplified Fenton reaction inside TNBC cells. Specifically, the Au nanorod core can convert NIR light energy into heat to induce massive production of intracellular H2 O2 , thereby the surface-decorated iron oxide nanoparticles (IONP) are being fueled for robust Fenton reaction. By exploiting the vulnerability of iron efflux in TNBC cells, such a self-fueling Fenton reaction leads to highly specific anti-TNBC efficacy with minimal cytotoxicity to normal cells. The PI3K/Akt/FoxO axis, intimately involved in the redox regulation and survival of TNBC, is demonstrated to be inhibited after the treatment. Consequently, precise in vivo orthotopic TNBC ablation is achieved under the guidance of IONP-enhanced magnetic resonance imaging. The results demonstrate the proof-of-concept of NIR-light-triggered self-fueling Fenton reagents against TNBC with low ferroportin levels.
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Neoplasias de Mama Triplo Negativas , Linhagem Celular Tumoral , Humanos , Peróxido de Hidrogênio , Ferro , Fosfatidilinositol 3-Quinases , Neoplasias de Mama Triplo Negativas/terapiaRESUMO
Morus species, commonly known as mulberry, is widely distributed in China. The mulberry tree is a high-value plant in agriculture. Morus australis is one of the major Morus species growing in Northern China. However, the biological properties of the main constituents of M. australis roots were not well studied. In the present study, through extensive chromatographic and spectral analysis, 12 phenolic compounds were isolated and identified from the M. australis roots. Compounds 1, 2, 8, 9 and 12 were isolated from M. australis roots for the first time. Antitumor activities of these polyphenols were studied on the A549 cell line. Compounds 1, 5 and 6 exhibited cytotoxicity on A549 cells and induced apoptosis in A549 cells via the intrinsic mitochondrial pathway. They also mediated inhibition of autophagic flux contributed cell death via the PI3k/Akt/mTOR pathway. In order to explore more potential bioactivities of these isolates, α-glucosidase, acetylcholinesterase and tyrosinase inhibitory activities were studied, and the results demonstrated that the inhibitory activity of these polyphenols on enzymes was not defined by their basic structural skeletons, but by the substituted position.
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Morus/química , Extratos Vegetais/química , Raízes de Plantas/química , Polifenóis/química , Células A549/efeitos dos fármacos , Acetilcolinesterase/química , Acetilcolinesterase/isolamento & purificação , Apoptose/efeitos dos fármacos , Movimento Celular , Proliferação de Células/efeitos dos fármacos , China , Humanos , Concentração Inibidora 50 , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Fenóis/análise , Fosfatidilinositol 3-Quinases , Polifenóis/farmacologia , alfa-Glucosidases/química , alfa-Glucosidases/isolamento & purificaçãoRESUMO
BACKGROUND: Pancreatic cancer (PDAC) is a highly invasive cancer with poor prognosis. Recent research has found that the transcription factor Yin Yang 1 (YY1) plays an inhibitory role in the development of pancreatic cancer. It has been reported that tubulin polymerisation-promoting protein (TPPP) plays an indispensable role in a variety of tumours, but its expression and role in pancreatic cancer have not yet been elucidated. METHODS: In this study, we performed ChIP-sequencing and found that YY1 directly binds to the promoter region of TPPP. The expression of TPPP in pancreatic cancer was detected by western blotting and immunohistochemistry. Four-week-old male BALB/c-nude mice were used to assess the effect of TPPP on pancreatic cancer. RESULTS: Immunohistochemistry revealed that TPPP was expressed at low levels in pancreatic cancer tissues, and was associated with blood vessel invasion. The results from vivo experiments have showed that TPPP could enhance the migration and invasion of pancreatic cancer. Further experiments showed that YY1 could inhibit the migration, invasion and angiogenesis of pancreatic cancer cells by downregulating TPPP via p38/MAPK and PI3K/AKT pathways. CONCLUSION: Our study demonstrates that TPPP may act as a promoter and may serve as a novel target for the treatment of pancreatic cancer.
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Movimento Celular/genética , Neovascularização Patológica/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Neoplasias Pancreáticas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fator de Transcrição YY1/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Animais , Linhagem Celular Tumoral , Xenoenxertos , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Invasividade Neoplásica/genética , Proteínas do Tecido Nervoso/genética , Neoplasias Pancreáticas/patologia , Transfecção , Fator de Transcrição YY1/genéticaRESUMO
BACKGROUND: Staphylococcal aureus (S. aureus) has become the leading causative pathogen of Prosthetic Joint Infection (PJI), which is the most devastating complication after arthroplasty surgeries. Due to the biofilm formation ability and emergence of multiple-drugs resistance strains of S. aureus, it has become an urgency to find new anti-staphylococcal agents to establish effective prophylaxis and treatment strategy for PJI. Extracted from a traditional Chinese herb, berberine is proved active in inhibiting S. aureus, while whether it exerts the same effect on PJI-related S. aureus remains unknown. This study aims to investigate the antimicrobial activity of berbrine against clinical derived PJI-related S. aureus and whether its inhibiting efficacy is associated with subtypes of S. aureus. METHODS: Eighteen PJI-associated S. aureus were collected and their Multi-locus Sequence Types (MLST) and susceptibility to berberine both in planktonic and biofilm form were investigated. Additionally, one S. aureus strain (ST1792) was selected from the group and its transcriptomic profiling in berberine incubation was performed. The statistical analyses were conducted using Student's t-test with SPSS 24.0(SPSS, IBM, USA). The data were expressed as the means ± standard deviation. Values of p < 0.05 were considered statistically significant. RESULTS: It was found out that the Minimum Inhibitory Concentration values of PJI-related S. aureus varied in a broad range (from 64 to 512 µg/ml) among different MLST subtypes and the bacteria were able to regain growth after 24 h in berberine of MIC value or higher concentrations. In addition, sub-inhibitory concentrations of berberine surprisingly enhanced biofilm formation in some S. aureus strains. CONCLUSION: Traditional medicine is utilised by a large number of individuals, which provides abundant resources for modern medical science. In our study, berberine was found bactericidal against PJI related S. aureus, however, its antibacterial property was impacted by the MLST subtypes of the bacteria, both in planktonic and biofilm growth forms.
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Antibacterianos/farmacologia , Berberina/farmacologia , Infecções Relacionadas à Prótese/microbiologia , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus , Humanos , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genéticaRESUMO
The greatest bottleneck for photothermal antibacterial therapy could be the difficulty in heating the infection site directly and specifically to evade the unwanted damage for surrounding healthy tissues. In recent years, infectious microenvironments (IMEs) have been increasingly recognized as a crucial contributor to bacterial infections. Here, based on the unique IMEs and rhenium trioxide (ReO3) nanocubes (NCs), a new specific photothermal antibacterial strategy is reported. These NCs synthesized by a rapid and straightforward space-confined on-substrate approach have good biocompatibility and exhibit efficient photothermal antibacterial ability. Especially when they are utilized in antibiofilm, the expression levels of biofilm-related genes (icaA, fnbA, atlE, and sarA for Staphylococcus aureus) can be effectively inhibited to block bacterial adhesion and formation of biofilm. Importantly, the ReO3 NCs can transform into hydrogen rhenium bronze (HxReO3) in an aqueous environment, making them relatively stable within the low pH of IMEs for photothermal therapy, while rapidly degradable within the surrounding healthy tissues to decrease photothermal damage. Note that under phosphate-buffered saline (PBS) at pH 7.4 without assistant conditions, these ReO3 NCs have the highest degradation rate among all known degradable inorganic photothermal nanoagents. This special and IME-sensitive selective degradability of the ReO3 NCs not only facilitates safe, efficient, and specific elimination of implant-related infections, but also enables effective body clearance after therapy. Solely containing the element (Re) whose atomic number is higher than clinic-applied iodine in all reported degradable inorganic photothermal nanoagents under the PBS (pH 7.4) without any assistant condition, the ReO3 NCs with high X-ray attenuation ability could be further applied to X-ray computed tomography imaging-guided therapy against implant-related infections. The present work described here is the first to adopt degradable inorganic photothermal nanoagents to achieve specific antibacterial therapy and inspires other therapies on this concept.
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Antibacterianos , Hipertermia Induzida , Implantes Experimentais/microbiologia , Nanoestruturas/química , Fototerapia , Infecções Estafilocócicas/prevenção & controle , Staphylococcus aureus/fisiologia , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óxidos/química , Rênio/químicaRESUMO
Ginsenoside Rb1 (GS-Rb1) is one of the most important active pharmacological extracts of the traditional Chinese medicine, ginseng, and there is extensive evidence of its cardioprotective properties. However, the microRNA (miR) targets of GS-Rb1 and the underlying mechanisms of GS-Rb1 and miR-21 in the progression of cardiomyocyte apoptosis have not been clearly elucidated. The aim of the current study was to investigate the impact of miR-21 and its target gene, programmed cell death protein 4 (PDCD4), on the protective effect of GS-Rb1 in cardiomyocytes injured by oxygen-glucose deprivation (OGD). The miR-21 expression levels were downregulated, and the percentage of the apoptotic cells and reactive oxygen species (ROS) was increased in OGD-cultured neonatal rat cardiomyocytes; however, the effects were reversed by GS-Rb1 treatment. It was demonstrated that GS-Rb1 could reduce intracellular ROS content, and the expression of cytochrome C and the pro-apoptosis protein, apoptosis regulator B-cell lymphoma associated X (Bax) protein while increasing the expression of the anti-apoptosis protein, apoptosis regulator Bcl-2. The target gene, PDCD4, was significantly upregulated in the OGD group; however, the expression of PDCD4 was inhibited by GS-Rb1 treatment. Furthermore, miR-21 inhibitor transfection reduced GS-Rb1-induced miR-21 upregulation compared with the OGD+GS-Rb1 group, indicating that the miR-21 was involved in the anti-apoptotic effect of GS-Rb1 in cardiomyocytes. The results of the current study highlighted that GS-Rb1 could target miR-21 and its target gene, PDCD4, to protect OGD-injured cardiomyocytes. The results of the current study may provide a novel insight for the treatment of myocardial infarction with Traditional Chinese Medicines, involving miRs as targets.
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BACKGROUND: Autophagy is a highly regulated biological process that mediates the degradation of intracellular components. It is required for tumor cell metabolism and homeostasis. Yin-Yang 1 (YY1) has been reported to be involved in autophagy in several carcinomas. However, its role in autophagy in pancreatic cancer, one of the deadliest human malignancies, is unknown. Here, we investigated the function of YY1 in pancreatic cancer cells autophagy and its mechanisms of action. METHODS: The activity of cells undergoing autophagy was assessed using transmission electron microscopy, immunofluorescence, and Western blotting. A luciferase activity assay, real-time quantitative polymerase chain reaction (RT-qPCR), and chromatin immunoprecipitation (ChIP) were also used to identify putative downstream targets of YY1. RESULTS: YY1 was confirmed to regulate autophagy in pancreatic cancer cells. It was found to directly regulate the expression of miR-30a, a known modulator of autophagy-associated genes. Furthermore, overexpression of miR-30a attenuated the pro-autophagic effects of YY1. CONCLUSIONS: Cumulatively, our data suggest that miR-30a acts in a feedback loop to modulate the pro-autophagic activities of YY1. Thus, autophagy in pancreatic cancer cells may be regulated, in part, by a tightly coordinated YY1/miR-30a regulatory circuit. These findings provide a potential druggable target for the development of treatments for pancreatic cancer.
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Autofagia/genética , MicroRNAs/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Fator de Transcrição YY1/metabolismo , Animais , Autofagossomos/metabolismo , Autofagossomos/ultraestrutura , Sequência de Bases , Linhagem Celular Tumoral , Retroalimentação Fisiológica , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Ligação Proteica , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The transcription regulator Yin Yang-1 (YY1) serves as a tumor suppressor in pancreatic ductal adenocarcinoma (PDAC). However, the function of YY1 in proliferation of PDAC cells remains to be clarified. In this study, we found that overexpression of YY1 suppressed proliferation and decreased the expression of long non-coding RNA (lncRNA) SOX2OT and its potential target gene SOX2 in PDAC cells. Luciferase reporter, electrophoretic mobility shift (EMSA), and chromatin immunoprecipitation (ChIP) assays revealed binding of YY1 to the SOX2OT promoter. Moreover, YY1 suppressed PDAC cell proliferation through SOX2OT transcriptional inhibition and subsequent decreased SOX2 expression. In addition, YY1 expression was statistically negatively correlated with SOX2OT and SOX2 expression in PDAC tissues and lower level expression of SOX2OT predicted better outcome in PDAC patients. These results confirmed the anti-proliferation effect of YY1 on PDAC cells, which was associated with SOX2 down-regulation in a SOX2OT-dependent mechanism. Although other undiscovered mechanisms may be involved in the YY1-mediated tumor suppression role, the present study suggests that SOX2OT may act as a tumor promotor in PDAC and may represent a valuable diagnostic and therapeutic target.
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Carcinoma Ductal Pancreático/patologia , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas/patologia , RNA Longo não Codificante/metabolismo , Fatores de Transcrição SOXB1/metabolismo , Fator de Transcrição YY1/metabolismo , Animais , Apoptose , Biomarcadores Tumorais , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Imunoprecipitação da Cromatina , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Estadiamento de Neoplasias , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Prognóstico , Regiões Promotoras Genéticas , RNA Longo não Codificante/genética , Fatores de Transcrição SOXB1/genética , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Fator de Transcrição YY1/genéticaRESUMO
The transcriptional regulator Yin Yang-1 (YY1) is a tumor suppressor known to be overexpressed in pancreatic cancer. We found that overexpression of YY1 promoted apoptosis and increased the expression and mitochondrial localization of the pro-apoptotic Bax protein in pancreatic cancer cell lines. Luciferase reporter, electrophoretic mobility shift (EMSA), and chromatin immunoprecipitation (ChIP) assays revealed binding of YY1 to the BAX promoter. Moreover, YY1 promoted pancreatic cancer cell apoptosis through Bax transcriptional activation and subsequent translocation of Bax to the mitochondrial membrane, leading to cytochrome c release, and caspase activation.YY1 and BAX are co-expressed in pancreatic cancer tissues and higher BAX expression predicts better outcomes for patients. The ability of YY1 to promote apoptosis in pancreatic cancer cells suggests it may represent a valuable diagnostic and therapeutic target.
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Apoptose/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pancreáticas/genética , Fator de Transcrição YY1/genética , Proteína X Associada a bcl-2/genética , Animais , Linhagem Celular Tumoral , Feminino , Humanos , Estimativa de Kaplan-Meier , Camundongos Endogâmicos BALB C , Camundongos Nus , Membranas Mitocondriais/metabolismo , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Prognóstico , Regiões Promotoras Genéticas/genética , Ligação Proteica , Transporte Proteico/genética , Transplante Heterólogo , Fator de Transcrição YY1/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
This study aimed to investigate whether or not ginkgo biloba extract (EGb 761) enhances peripheral nerve regeneration and vascularization after repair using acellular nerve allografts (ANA). Seventy-two Sprague-Dawley rats were randomly divided into three experimental groups: a unilateral 15-mm sciatic nerve defect was created and repaired with an autologous graft (autograft group); the same defect was repaired with an 18 mm ANA with an i.p. injection of normal saline for 10 days (saline group); and in the final group, the same defect was repaired with an 18 mm ANA with an i.p. injection of EGb 761 for 10 days (EGb 761 group). Axon outgrowth and vascularization were evaluated by immunocytochemistry 14 days post-implantation. The expression of genes associated with angiogenesis was analyzed by real-time polymerase chain reaction (PCR) seven days post-implantation. Compared with the saline group, rats in the EGb 761 group significantly increased the number of myelinated fibers and the average diameter of the nerves within the graft. There is no significant difference between the EGb 761 group and the autograft group. The expression of CD34 and NF200 was significantly higher in the EGb 761 group than in the saline group. Additionally, EGb 761 treatment increased the expression of several angiogenesis-related genes, including Vegf, SOX18, Prom 1, and IL-6. In conclusion, ANA repair with EGb 761 treatment demonstrates effects on peripheral nerve regeneration and vascularization that are equal to those of autologous graft repair, and that are superior to ANA repair alone.
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Aloenxertos/irrigação sanguínea , Neovascularização Fisiológica/efeitos dos fármacos , Regeneração Nervosa/efeitos dos fármacos , Extratos Vegetais/farmacologia , Nervo Isquiático/transplante , Aloenxertos/efeitos dos fármacos , Animais , Antígenos CD34/metabolismo , Axônios/efeitos dos fármacos , Modelos Animais de Doenças , Ginkgo biloba , Imuno-Histoquímica , Masculino , Músculos/efeitos dos fármacos , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/ultraestrutura , Tamanho do Órgão/efeitos dos fármacos , Ratos Sprague-Dawley , Nervo Isquiático/efeitos dos fármacos , Nervo Isquiático/patologia , Nervo Isquiático/ultraestruturaRESUMO
OBJECTIVE: To investigate the vasoconstriction effect of Ixeris sonchifolia in rat thoracic aortic rings and the underlying mechanisms. METHOD: I. sonchifolia 10-160 g x L(-1) was cumulatively added into organ bath to observe the isometric tension of thoracic aortic rings with intact endothelium or denuded endothelium in basal tension, preconstricted by phenylephrine (PE) or potassium chloride (KCl), and thoracic aortic rings with intact endothelium preincubated frist with captopril, phosphoramidon and indomethacin, respectively, then preconstricted by PE and KCl. The response was recorded and expressed by "relative contraction". RESULT: Cumulative administration of I. sonchifolia 10-160 g x L(-1) did not affect the vasomotion of aortic rings with endothelium or without endothelium in basal tension. Exposure of intact endothelium rings preconstricted by PE or KCl to I. sonchifolia at concentration (20-160 g x L(-1) induced a significant constriction, which was inhibited by preincubation with captopril, but was not inhibited by preincubation with phosphoramidon or indomethacin. Exposure of endothelium-denuded rings preconstricted by PE or KCl to I. sonchifolia at concentration (10 to approximately 160 g x L(-1) did not effect the vasoconstriction. CONCLUSION: The results indicate that I. sonchifolia (20 to approximately 160 g x L(-1) can contract the rat thoracic aortic rings with endothelium. The effect of contraction may enhance angiotensin converting enzyme activity and promote endothelium to synthesize angiotensin II. It has no relationship to endothelin or thromboxane A2.
Assuntos
Aorta Torácica/efeitos dos fármacos , Asteraceae/química , Medicamentos de Ervas Chinesas/farmacologia , Vasoconstrição/efeitos dos fármacos , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Aorta Torácica/fisiologia , Captopril/farmacologia , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/isolamento & purificação , Endotélio Vascular/fisiologia , Técnicas In Vitro , Masculino , Fenilefrina/farmacologia , Plantas Medicinais/química , Ratos , Ratos Sprague-Dawley , Vasoconstritores/farmacologiaRESUMO
<p><b>OBJECTIVE</b>To investigate the vasoconstriction effect of Ixeris sonchifolia in rat thoracic aortic rings and the underlying mechanisms.</p><p><b>METHOD</b>I. sonchifolia 10-160 g x L(-1) was cumulatively added into organ bath to observe the isometric tension of thoracic aortic rings with intact endothelium or denuded endothelium in basal tension, preconstricted by phenylephrine (PE) or potassium chloride (KCl), and thoracic aortic rings with intact endothelium preincubated frist with captopril, phosphoramidon and indomethacin, respectively, then preconstricted by PE and KCl. The response was recorded and expressed by "relative contraction".</p><p><b>RESULT</b>Cumulative administration of I. sonchifolia 10-160 g x L(-1) did not affect the vasomotion of aortic rings with endothelium or without endothelium in basal tension. Exposure of intact endothelium rings preconstricted by PE or KCl to I. sonchifolia at concentration (20-160 g x L(-1) induced a significant constriction, which was inhibited by preincubation with captopril, but was not inhibited by preincubation with phosphoramidon or indomethacin. Exposure of endothelium-denuded rings preconstricted by PE or KCl to I. sonchifolia at concentration (10 to approximately 160 g x L(-1) did not effect the vasoconstriction.</p><p><b>CONCLUSION</b>The results indicate that I. sonchifolia (20 to approximately 160 g x L(-1) can contract the rat thoracic aortic rings with endothelium. The effect of contraction may enhance angiotensin converting enzyme activity and promote endothelium to synthesize angiotensin II. It has no relationship to endothelin or thromboxane A2.</p>
Assuntos
Animais , Masculino , Ratos , Inibidores da Enzima Conversora de Angiotensina , Farmacologia , Aorta Torácica , Fisiologia , Asteraceae , Química , Captopril , Farmacologia , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas , Farmacologia , Endotélio Vascular , Fisiologia , Técnicas In Vitro , Fenilefrina , Farmacologia , Plantas Medicinais , Química , Ratos Sprague-Dawley , Vasoconstrição , Vasoconstritores , FarmacologiaRESUMO
OBJECTIVE: To evaluate the therapeutic effect and safety of acupoint sticking therapy for facial paralysis. METHODS: Search the literatures in the whole paper databank of China figure medical library (Jan. 1994-Dec. 2004) and China Biomedical Literature Disk Databank (Jan. 1995-Dec. 2004). Meta-analysis was conducted with RevMan 4. 2. 5 software. RESULTS: Sixteen controlled trials involving 2 157 patients were included. Meta-analysis indicated that there was high statistically difference between the acupoint sticking therapy and simple acupuncture therapy or Western medicine therapy. CONCLUSION: The acupoint sticking therapy is effective and safe for facial paralysis.