RESUMEN
Meningioma is a prevalent intracranial malignancy known for its aggressive growth. Circular RNAs (circRNAs) play a crucial role in the development of various cancers. However, their involvement in meningioma remains understudied. This study aimed to investigate the function and underlying mechanism of hsa_circ_0004872 in meningioma. The molecular expression of hsa_circ_0004872, PD-L1 and EIF4A3 was identified by RT-qPCR and/or western blot assays. Cell viability, migration, and invasion were assessed through CCK-8 and Transwell assays, respectively. Cytotoxicity was determined using an LDH assay, and cell apoptosis was monitored by flow cytometry. The RNA and protein interactions were assessed through RNA-protein immunoprecipitation (RIP) and RNA pull down analyses. Our findings revealed that hsa_circ_0004872 expression was significantly downregulated in both meningioma tissue samples and cells. Overexpression of hsa_circ_0004872 inhibited the proliferation, metastasis, and immune escape of meningioma cells, as well as enhanced the cytotoxicity of CD8+ T cells by suppressing PD-L1. Furthermore, hsa_circ_0004872 directly interacted with EIF4A3, leading to the degradation of PD-L1 mRNA. Finally, inhibiting EIF4A3 improved the proliferation, metastasis, and immune escape of meningioma cells, as well as the cytotoxicity of CD8+ T cells. Our study demonstrated that hsa_circ_0004872 mitigated the proliferation, metastasis,and immune escape of meningioma cells by targeting the EIF4A3/PD-L1 axis. These findings suggested that hsa_circ_0004872 and EIF4A3 might serve as promising biological markers and therapeutic targets for meningioma treatment.
Asunto(s)
Antígeno B7-H1 , Proliferación Celular , Factor 4A Eucariótico de Iniciación , Neoplasias Meníngeas , Meningioma , ARN Circular , Meningioma/patología , Meningioma/inmunología , Meningioma/genética , Meningioma/metabolismo , Humanos , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , ARN Circular/genética , Neoplasias Meníngeas/patología , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/inmunología , Neoplasias Meníngeas/metabolismo , Factor 4A Eucariótico de Iniciación/genética , Factor 4A Eucariótico de Iniciación/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Movimiento Celular , Escape del Tumor , Apoptosis , ARN Helicasas DEAD-boxRESUMEN
Objective: Ferroptosis is a novel cell death process which displays a promising role in cancer treatment. However, clinically available drugs targeting ferroptosis are rarely used, and yet there are no studies reporting on inducing ferroptosis via Chinese herbal extracts. Here we explored the tumor inhibition effects of Ganoderma lucidum (G. lucidum) on oral squamous cell carcinoma (OSCC). Specifically, we aimed to clarify the biological mechanism of components in the dietary, aqueous-soluble sporoderm-removed G. lucidum spore powder (A-GSP). Methods: Preliminary transcriptome analysis revealed the significant enrichment of the ferroptosis pathway. Cellular Fe2+, glutathione (GSH), malondialdehyde (MDA), reactive oxygen species (ROS) and lipid peroxide levels were measured to identify ferroptosis occurrence. Western blotting was used to measure ferroptosis-related proteins. Changes in mitochondria morphology and function were observed with transmission electron microscopy (TEM) and ATP detection assays. Ferroptosis inhibitor ferrostatin-1 was then used to verify the anti-tumor effects of A-GSP. Finally, nude mice xenograft models of oral cancer confirmed that A-GSP inhibited tumor growth. Results: A-GSP promoted ferroptosis in oral cancer cells by inducing Fe2+ influx, GSH depletion, as well as lipid peroxide and ROS accumulation. Ferroptosis-related proteins exhibited corresponding changes, particularly Acyl-coA synthetase long chain family member 4 (ACSL4) increase and glutathione peroxidase 4 (GPX4) decrease. A-GSP considerably lowered mitochondrial volume and ridge number, while significantly decreasing ATP production. Ferrostatin-1 reversed all of these A-GSP-induced changes. In vivo, A-GSP exerted a ferroptosis-mediated tumor-suppressing effect without observable adverse reactions. Conclusions: Our findings demonstrate the therapeutic potential of A-GSP for treating patients with OSCC by targeting ferroptosis.
RESUMEN
Whereas mechanics theories for isotropic materials are almost matured, only linear elastic theories for composites were essentially established. This is because only homogenized or approximated stresses are obtainable for a composite. Its mechanical properties must be estimated on a true stress level. According to Eshelby, the true stresses of the fiber are the same as its homogenized counterparts. The true stress theory for the matrix was systematically established by the author, and is reviewed and summarized in the paper. An Excel table-based program for calculating all of the possible true stress components is provided as a supplement for the reader to download. As most composite failures are caused by matrix failures, the true stress theory plays a predominant role in estimating the composite properties outside a linear elastic range. Some challenging composite failures were resolved upon the matrix true stresses, and are highlighted in the paper.
RESUMEN
Essentially, every failure of a short fiber reinforced composite (SFRC) under tension is induced from a matrix failure, the prediction of which is of fundamental importance. This can be achieved only when the homogenized stresses of the matrix are converted into true values in terms of stress concentration factors (SCFs) of the matrix in an SFRC. Such an SCF cannot be determined in the classical way. In this paper, a closed-form formula for the longitudinal tensile SCF in the SFRC is derived from the matrix stresses determined through an elastic approach. The other directional SCFs in an SFRC are the same as those in a continuous fiber composite already available. A bridging model was used to calculate the homogenized stresses explicitly, and a failure prediction of the SFRC with arbitrary fiber aspect ratio and fiber content was made using only the original constituent strength data. Results showed that the volume fraction, the aspect ratio, and the orientation of the fiber all have significant effect on the tensile strength of an SFRC. In a certain range, the tensile strength of an SFRC increases with the increase in fiber aspect ratio and fiber volume content, and the strength of the oriented short fiber is higher than that of the random short fiber arrangement. Good correlations between the predicted and the available measured strengths for a number of SFRCs show the capability of the present method.
RESUMEN
MUS81 complex, exhibiting endonuclease activity on specific DNA structures, plays an influential part in DNA repair. Research has proved that MUS81 is dispensable for embryonic development and cell viability in mammals. However, an intricate picture has emerged from studies in which discrepant gene mutations completely alter the role of MUS81 in human cancers. Here, we review the recent understanding of how MUS81 functions in tumors with distinct genetic backgrounds and discuss the potential therapeutic strategies targeting MUS81 in cancer.
RESUMEN
Nonlinear properties of composite materials are essential for their engineering application. In this work, a three-phase micromechanics bridging model is employed to evaluate the nonlinear behavior of a composite from properties of fiber, matrix and interphase. It is assumed that the matrix elastoplasticity and the interface damage are two major sources of the nonlinearity. The former is described by the J2 flow rule. The latter is approximated by an interphase with stiffness degradation. For an interphase, an equivalent damage stress is introduced to account for the effect of normal and shear stress on the interface damage growth. Further, an explicit empirical equation is developed to relate the equivalent damage stress and the stiffness degradation of an interphase. The present elasto-plastic damage model is validated by comparing with experimental data of a series of composites under off-axis tensile loads.
RESUMEN
Immunotherapies have emerged as the most promising area in cancer treatments in recent years. CD8+ T cells, as one of the primary effector cells of anticancer immunity, however, when infiltrating in cancer tissues, are generally in dysfunctional states termed T-cell exhaustion. Exhausted CD8+ T cells are characterized by impaired activity and proliferative ability, increased apoptotic rate and reduced production of effector cytokines. Such dysfunctional CD8+ T cells serve as a barrier in successful cancer elimination. Investigation on the mechanism of T-cell exhaustion was aiming to sustain or restore the efficiency of CD8+ T cells infiltrating in cancer, which may help to develop novel strategies to overcome cancer. Recent studies have found several vital mechanisms of CD8+ T-cell exhaustion and provided novel avenues through targeting CD8+ T-cell exhaustion to enhance anticancer immunity. Here, we review the recent progress in the study of CD8+ T-cell exhaustion to make a summary and to provide a framework for further researches.
Asunto(s)
Linfocitos T CD8-positivos/inmunología , Inmunoterapia , Linfocitos Infiltrantes de Tumor/inmunología , Neoplasias/inmunología , Animales , Humanos , Neoplasias/terapiaRESUMEN
In chronic infection and cancer, T cells gradually become exhausted because of the persistent stimulation by antigens. In this process, the overexpression of multiple inhibitory receptors is induced, the production of effective cytokines decreases and the cytotoxicity and proliferation of T cells impairs, all contributing to the failure of T cells in fighting against cancer. Reversing T-cell exhaustion is a promising immunotherapy for cancer that has yielded encouraging results. In this review, we discuss the genomic and epigenomic landscape of T-cell exhaustion in cancer. Also, we introduce the relevant therapeutic interventions for T-cell exhaustion in clinical trials.
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Epigenómica , Genómica , Inmunoterapia , Neoplasias/genética , Neoplasias/inmunología , Linfocitos T/inmunología , Linfocitos T/metabolismo , Animales , Citocinas/metabolismo , Humanos , Inmunomodulación , Neoplasias/terapia , Linfocitos T Citotóxicos/inmunologíaRESUMEN
Elasto-plastic models for composites can be classified into three categories in terms of a length scale, i.e., macro scale, meso scale, and micro scale (micromechanics) models. In general, a so-called multi-scale model is a combination of those at various length scales with a micromechanics one as the foundation. In this paper, a critical review is made for the elastoplastic models at the micro scale, and a comparative study is carried out on most popular analytical micromechanics models for the elastoplastic behavior of long fibrous composites subjected to a static load, meaning that creep and dynamic response are not concerned. Each model has been developed essentially following three steps, i.e., an elastic homogenization, a rule to define the yielding of a constituent phase, and a linearization for the elastoplastic response. The comparison is made for all of the three aspects. Effects of other issues, such as the stress field fluctuation induced by a high contrast heterogeneity, the stress concentration factors in the matrix, and the different approaches to a plastic Eshelby tensor, are addressed as well. Correlation of the predictions by different models with available experimental data is shown.
RESUMEN
During chronic viral infection or cancer, the immune system usually induces a corresponding immune response against pathogens or cancer cells so as to prevent worsening disease. T cell exhaustion in which reduced and dysfunctional effector T cells lead to immune escape is one of the mechanisms that pathogens or cancer cells get rid of control from the immune system. In this review, we discuss some mechanisms associated with T cell exhaustion and enumerate current methods of reversing T cell exhaustion. We also summarize current targeted treatment strategies and put forward following aspects that required to research.
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Anergia Clonal , Neoplasias/inmunología , Linfocitos T/inmunología , Virosis/inmunología , Animales , Humanos , Neoplasias/patología , Neoplasias/virología , Linfocitos T/patología , Virosis/patologíaRESUMEN
A series of Matijin-Su (MTS, (2S)-2-{[(2S)-2-benzamido-3-phenylpropanoyl]amino}-3-phenylpropyl acetate) derivatives were synthesized and evaluated for their anti-HBV and cytotoxic activities in vitro. Six compounds (4g, 4j, 5c, 5g, 5h and 5i) showed significant inhibition against HBV DNA replication with the IC50 values in range of 2.18 - 8.55 µm, which were much lower than that of positive control lamivudine (IC50 82.42 µm). In particular, compounds 5h (IC50 2.18 µm; SI 151.59) and 5j (IC50 5.65 µm; SI 51.16) displayed relatively low cytotoxicities, resulting in high SI values. Notably, besides the anti-HBV DNA replication activity, compound 4j also exhibited more potent in vitro cytotoxic activity than 5-fluorouracil in two hepatocellular carcinoma cell (HCC) lines (QGY-7701 and SMMC-7721), indicating that 4j may be a promising lead for the exploration of drugs with dual therapeutic effects on HBV infection and HBV-induced HCC.
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Antineoplásicos/farmacología , Antivirales/farmacología , Dipéptidos/farmacología , Virus de la Hepatitis B/efectos de los fármacos , Hepatitis B Crónica/tratamiento farmacológico , Antineoplásicos/síntesis química , Antineoplásicos/química , Antivirales/síntesis química , Antivirales/química , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Dipéptidos/síntesis química , Dipéptidos/química , Relación Dosis-Respuesta a Droga , Ensayos de Selección de Medicamentos Antitumorales , Humanos , Pruebas de Sensibilidad Microbiana , Conformación Molecular , Relación Estructura-ActividadRESUMEN
ETHNOPHARMACOLOGY RELEVANCE: Water dropwort [Oenanthe javanica (O. javanica)] is an aquatic perennial herb cultivated in East Asian countries. It has been popularly used in traditional Chinese medicine which is beneficial for the treatment of many diseases, including jaundice and various types of chronic and acute hepatitis. In the present study, we investigated the hepatoprotective effect of total phenolics from O. javanica (TPOJ) against D-galactosamine (D-GalN) induced liver injury in mice. MATERIAL AND METHODS: The hepatoprotective activity of TPOJ (125, 250 and 500mg/kg) was investigated on D-GalN (800mg/kg)-induced liver damages in mice. Blood and liver were collected for biochemical and microscopic analysis. RT-PCR was used to determine the changes in hepatic nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression. Protein levels of iNOS, COX-2, superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were determined by western blotting. RESULTS: In the animal studies, TPOJ could improve the survival of acute liver failure model significantly and prevente the D-GalN-induced elevation of the serum enzymatic markers and nonenzymatic markers levels significantly. Meanwhile, TPOJ-treatment decreased the malondialdehyde (MDA) level and elevated the content of glutathione (GSH) in the liver as compared to those in the D-GalN group. Hepatic activities and protein expressions of antioxidative enzymes, including SOD, GPx, and CAT were enhanced dose dependently with TPOJ. At the same time, application of TPOJ effectively suppressed the D-GalN-induced proinflammatory mRNA and protein expression of iNOS and COX-2. Subsequently, the serum levels of proinflammatory mediators, nitric oxide (NO) and prostaglandin E2 (PGE2) were reduced. Additionally, histological analyses also showed that TPOJ reduced the extent of liver lesions induced by D-GalN. CONCLUSION: Our investigation demonstrated the hepatoprotective activity of TPOJ and revealed that TPOJ attributed its significance in the traditional use for treating liver diseases.
Asunto(s)
Galactosamina/toxicidad , Fallo Hepático Agudo/inducido químicamente , Fallo Hepático Agudo/tratamiento farmacológico , Oenanthe/química , Fenoles/farmacología , Extractos Vegetales/farmacología , Animales , Relación Dosis-Respuesta a Droga , Masculino , Ratones , Estrés Oxidativo/efectos de los fármacos , Fenoles/administración & dosificación , Fenoles/química , Fitoterapia , Extractos Vegetales/administración & dosificación , Extractos Vegetales/química , Silimarina/administración & dosificación , Silimarina/farmacologíaRESUMEN
ETHNOPHARMACOLOGY RELEVANCE: The decoction of the flowers of Abelmoschus manihot (L.) Medic was traditionally used for the treatment of jaundice and various types of chronic and acute hepatitis in Anhui and Jiangsu Provinces of China for hundreds of years. Phytochemical studies have indicated that total flavonoids extracted from flowers of A. manihot (L.) Medic (TFA) were the major constituents of the flowers. Our previous studies have investigated the hepatoprotective effects of the TFA against carbon tetrachloride (CCl4) induced hepatocyte damage in vitro and liver injury in vivo. This study aimed to investigate the protective effects and mechanisms of TFA on α-naphthylisothiocyanate (ANIT)-induced cholestatic liver injury in rats. MATERIAL AND METHODS: The hepatoprotective activities of TFA (125, 250 and 500mg/kg) were investigated on ANIT-induced cholestatic liver injury in rats. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were used as indices of hepatic cell damage and measured. Meanwhile, the serum levels of alkaline phosphatase (ALP), gamma-glutamyltransferase (GGT), total bilirubin (TBIL), direct bilirubin (DBIL), and total bile acid (TBA) were used as indices of biliary cell damage and cholestasis and evaluated. Hepatic malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione transferase (GST), tumor necrosis factor-α (TNF-α) and nitric oxide (NO) were measured in the liver homogenates. The bile flow in 4h was estimated and the histopathology of the liver tissue was evaluated. Furthermore, the expression of transporters, bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2), and Na(+)-taurocholate cotransporting polypeptide (NTCP) were studied by western blot and reverse transcription-quantitative real-time polymerase chain reaction (RT-PCR) to elucidate the protective mechanisms of TFA against ANIT-induced cholestasis. RESULTS: The oral administration of TFA to ANIT-treated rats could reduce the increases in serum levels of ALT, AST, LDH, ALP, GGT, TBIL, DBIL and TBA. Decreased bile flow by ANIT was restored with TFA treatment. Concurrent administration of TFA reduced the severity of polymorphonuclear neutrophil infiltration and other histological damages, which were consistent with the serological tests. Hepatic MDA and GSH contents in liver tissue were reduced, while SOD and GST activities, which had been suppressed by ANIT, were elevated in the groups pretreated with TFA. With TFA intervention, levels of TNF-α and NO in liver were decreased. Additionally, TFA was found to increase the expression of liver BSEP, MRP2, and NTCP in both protein and mRNA levels in ANIT-induced liver injury with cholestasis. CONCLUSION: TFA exerted protective effects against ANIT-induced liver injury. The possible mechanisms could be related to anti-oxidative damage, anti-inflammation and regulating the expression of hepatic transporters. It layed the foundation for the further research on the mechanisms of cholestasis as well as the therapeutic effects of A. manihot (L.) Medic for the treatment of jaundice.
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Abelmoschus/química , Colestasis/prevención & control , Flavonoides/farmacología , 1-Naftilisotiocianato/toxicidad , Administración Oral , Animales , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Flavonoides/administración & dosificación , Flavonoides/aislamiento & purificación , Flores , Hígado/efectos de los fármacos , Hígado/patología , Masculino , Ratas , Ratas WistarRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The decoction of the flowers of Abelmoschus manihot (L.) Medic is traditionally used for the treatment of jaundice and various types of chronic and acute hepatitis in Anhui and Jiangsu Provinces of China. Phytochemical studies have indicated that total flavonoids extracted from flowers of Abelmoschus manihot (L.) Medic (TFA) were the major constituents of the flowers. The present study was designed to investigate the hepatoprotective effect of the plant extracts against carbon tetrachloride (CCl4) induced hepatocyte damage in vitro and liver injury in vivo. MATERIAL AND METHODS: In the in vitro studies, freshly isolated rat hepatocytes were exposed to CCl4 (1%) along with/without various concentrations of TFA (4.5-72mg/L). Cell damage was assessed by the trypan blue exclusion method and alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) in the medium were analyzed. In the in vivo studies, the hepatoprotective activity of TFA (125, 250 and 500mg/kg) were investigated on CCl4-induced liver damages in mice. The levels of ALT, AST and ALP, gamma glutamyltransferase (γ-GT), tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) and nitric oxide (NO) were determined in serum. Hepatic malondialdehyde (MDA), glutathione (GSH), superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione transferase (GST) were measured in the liver homogenates. Cytokine transcript levels of TNF-α, IL-1ß and inducible nitric oxide synthase (iNOS) in the liver tissues of mice were measured using reverse transcription-polymerase chain reaction (RT-PCR). Livers were dissected out and evaluated for histomorphological changes. RESULTS: A concentration-dependent increase in the percentage viability was observed when CCl4-exposed hepatocytes were treated with different concentrations of TFA. Levels of ALT, AST and ALP in the medium were significantly decreased. In the animal studies, TFA showed significant protection with the depletion of ALT, AST, ALP and γ-GT in serum as was raised by the induction of CCl4. Moreover, TFA decreased the MDA level and elevated the content of GSH in the liver as compared to those in the CCl4 group. Furthermore, activities of antioxidative enzymes, including SOD, GPx, CAT and GST, were enhanced dose dependently with TFA. Meanwhile, the inflammatory mediators (e.g., TNF-α, IL-1ß and NO) were inhibited by TFA treatment both at the serum and mRNA levels. Additionally, histological analyses also showed that TFA reduced the extent of liver lesions induced by CCl4. CONCLUSION: These results suggested that TFA protected mice against CCl4-induced liver injury through antioxidant stress and antiinflammatory effects. This finding justified the use of this plant in traditional medicine for the treatment of liver disease.
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Abelmoschus/química , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Medicamentos Herbarios Chinos/uso terapéutico , Flavonoides/uso terapéutico , Hepatocitos/efectos de los fármacos , Hígado/efectos de los fármacos , Animales , Tetracloruro de Carbono/toxicidad , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Enfermedad Hepática Inducida por Sustancias y Drogas/enzimología , Enfermedad Hepática Inducida por Sustancias y Drogas/inmunología , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/farmacología , Flavonoides/aislamiento & purificación , Flavonoides/farmacología , Flores/química , Hepatocitos/enzimología , Hepatocitos/inmunología , Hepatocitos/patología , Mediadores de Inflamación/metabolismo , Hígado/enzimología , Hígado/inmunología , Hígado/patología , Pruebas de Función Hepática , Masculino , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
OBJECTIVE: To observe the toxicity of hyperoside in rat embryo-fetal development, in order to provide preference for safe use of drugs during gestation period. METHOD: Healthy pregnant rats were randomly divided into hyperosid groups (30, 175, 1000 mg x kg(-1) x d(-1)), the positive control group (cyclophosphamide, 7 mg x kg(-1) x d(-1)) and the solvent control group (1% aqueous carboxymethylcellulose). These rats were orally administered with hyperosid or vehicle during 6-15 d after gestation and subcutaneously injected with cyclophosphamide during 11-13 d. Maternal clinical sign, abortions, premature deliveries and body weight were monitored throughout gestation. At termination (gestation days 20), pregnant females were evaluated for clinical symposiums, weight change, corpora lutea count, existence and death of embryos; live fetuses were examined for gender, external, visceral and skeletal malformation and variations. RESULT: All pregnant rats showed no significant abnormality in appearance, viscera and skeletal development. However, there was a difference between the high-dose group of hyperoside and negative control group in the fetus body weight, the length of the embryos and the length of tail (P < 0.05). CONCLUSION: Pregnant women are suggested to cautiously use hyperoside because it shows certain impact on development of fetal rats under the experimental conditions.
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Abelmoschus/química , Medicamentos Herbarios Chinos/toxicidad , Desarrollo Embrionario/efectos de los fármacos , Desarrollo Fetal/efectos de los fármacos , Quercetina/análogos & derivados , Animales , Femenino , Tamaño de la Camada/efectos de los fármacos , Masculino , Embarazo , Quercetina/toxicidad , Ratas , Ratas WistarRESUMEN
A series of Matijing-Su (MTS, N-(N-benzoyl-l-phenylalanyl)-O-acetyl-L-phenylalanol) derivatives were synthesized and evaluated for their anti-hepatitis B virus (HBV) activity in 2.2.15 cells. The IC(50) of compounds 14a (0.71 µM), 13c (2.85 µM), 13b (4.37 µM), etc. and the selective index of 13g (161.01), 13c (90.45), 13a (85.09) etc. of the inhibition on the replication of HBV DNA were better than those of the positive control lamivudine (IC(50): 82.42 µM, SI: 41.59). Compounds 13o, 13p, and 16a also exhibited significant anti-HBV activity.
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Antivirales/síntesis química , Antivirales/farmacología , Dipéptidos/farmacología , Virus de la Hepatitis B/efectos de los fármacos , Antivirales/química , Línea Celular , Dipéptidos/síntesis química , Dipéptidos/química , Relación Dosis-Respuesta a Droga , Humanos , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Estereoisomerismo , Relación Estructura-Actividad , Replicación Viral/efectos de los fármacosRESUMEN
In order to improve both safety and efficacy of cancer chemotherapy of titanocene dichloride and overcome the shortcomings such as instability and short half-life in the human body, we report a controlled release system of titanocene dichloride by electrospun fiber and its in vitro antitumor activity against human lung tumor spca-1 cells. The system was developed by electrospinning. The release profiles of titanocene dichloride in PBS were researched by UV-Vis spectrophotometer. In vitro antitumor activities of the fibers were examined by MTT method. Titanocene dichloride was well incorporated in biodegradable poly(L-lactic acid) fibers. XRD results suggest that titanocene dichloride exists in the amorphous form in the fibers. The controlled release of titanocene dichloride can be gained for long time. MTT showed actual titanocene dichloride content 40, 80, 160 and 240 mg/L from the fibers mat, cell growth inhibition rates of 11.2%, 22.1%, 44.2% and 68.2% were achieved, respectively. The titanocene dichloride released has obvious inhibition effect against lung tumor cells. The system has an effect of controlled release of titanocene dichloride and may be used as an implantable anticancer drug in clinical applications in the future.
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Antineoplásicos/administración & dosificación , Preparaciones de Acción Retardada , Sistemas de Liberación de Medicamentos , Ácido Láctico , Compuestos Organometálicos/administración & dosificación , Polímeros , Antineoplásicos/farmacología , Línea Celular Tumoral , Semivida , Humanos , Compuestos Organometálicos/farmacología , PoliésteresRESUMEN
The objectives of this work are twofold. Firstly, while most work on electrospinning is limited to the development of only functional materials, a structural application of electrospun nanofibers is explored. Secondly, a drug-loaded tissue suture is fabricated and its various properties are characterized. Braided drug-loaded nanofiber sutures are obtained by combining an electrospinning process with a braiding technique followed by a coating procedure. Two different electrospinning techniques, i.e. blend and coaxial electrospinning, to incorporate a model drug cefotaxime sodium (CFX-Na) into poly(L-lactic acid) (PLLA) nanofibers have been applied and compared with each other. Properties of the braided drug-loaded sutures are characterized through a variety of methods including SEM, TEM and tensile testing. The results show that the nanofibers had a preferable micromorphology. The drug was incorporated into the polymer nanofibers homogeneously, with no cross-linking. The nanofibers maintained their fibrous structures. An in vitro release study indicates that the drug-loaded nanofibers fabricated by blend electrospinning and coaxial electrospinning had a different drug release behavior. An inhibition zone experiment shows that both sutures obtained from the nanofibers of the different electrospinning techniques had favorable antibacterial properties. The drug-loaded sutures had preferable histological compatibility performance compared with commercial silk sutures in an in vivo comparative study.
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Antibacterianos/administración & dosificación , Cefotaxima/administración & dosificación , Ácido Láctico/química , Nanofibras/química , Nanotecnología/métodos , Animales , Antibacterianos/farmacología , Cefotaxima/farmacología , Electroquímica/instrumentación , Electroquímica/métodos , Diseño de Equipo , Escherichia coli/efectos de los fármacos , Nanofibras/ultraestructura , Nanotecnología/instrumentación , Ratas , Ratas Sprague-Dawley , Staphylococcus aureus/efectos de los fármacos , SuturasRESUMEN
The aim of this study is to investigate the effects and mechanism of extract of Apocynum venetum (AV) on kidneys of streptozotocin-induced diabetic rats. Diabetes mellitus (DM) was induced in rats by intraperitoneal injection of streptozotocin (STZ). The indexes of the blood glucose, renal function and oxidative stress were observed. The DM rats were administrated with the AV for 8 weeks, the above-mentioned indexes were detected. The blood glucose level, BUN, 24 h urine protein excretion, urine volume, renal index, renal cortex's MDA level in model groups all increased significantly. Renal cortex's SOD and GSH activities decreased significantly compared with the normal control group (P < 0.05). The above-mentioned indexes were significantly improved by the AV treatment (P < 0.05). AV have protective effects on renal function of kidneys of streptozotocin-induced diabetic rats, and maybe via inhibition of the renal oxidative stress.
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Apocynum/química , Diabetes Mellitus Experimental/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Corteza Renal/patología , Animales , Glucemia/metabolismo , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Diabetes Mellitus Experimental/sangre , Diabetes Mellitus Experimental/patología , Medicamentos Herbarios Chinos/aislamiento & purificación , Fructosamina/sangre , Glutatión Peroxidasa/metabolismo , Riñón/fisiopatología , Masculino , Malondialdehído/metabolismo , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar , Superóxido Dismutasa/metabolismoRESUMEN
The development of functionalized braided wires coated with chitosan that can be used for tissue suturing and tissue regeneration is the subject of this work. Poly(L: -lactic acid) (PLLA) braided wires were successfully fabricated by combining an electrospinning technique and alignment collection with a mini-type braiding method. The resulting PLLA wires with and without chitosan coating were characterized through a variety of methods including scanning electron microscopy (SEM), X-ray photoelectronic spectra (XPS) and tensile mechanical testing. Hemolytic property, kinetic hemostasis behavior, platelet adhesion, erythrocyte adhesion, and water uptake ability of the wires were explored. The results showed that a nearly comparable mechanical behavior of the braided wires with some commercial suture could be obtained with well-aligned fibers, and no significant difference in tensile performances were recognized with and without the introduction of chitosan. The PLLA wires coated with chitosan were found to have better prohemostatic activity than those without a chitosan coating.