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Phototherapy (PT), including photodynamic therapy (PDT) and photothermal therapy (PTT), has recently achieved significant advances in antitumor and antiinfection therapy. Sonodynamic therapy (SDT), as a novel noninvasive therapy with a deeper penetration depth (>8 cm), fewer side effects and non-phototoxicity than PT, has drawn much attention in recent years. However, both PT and SDT have intrinsic limitations. By combining PT with SDT, the dualmodel therapy with advanced sensitizers overcome the intrinsic limitations and show higher efficacy than traditional monotherapy. Moreover, the photo-diagnosis modality could be easily integrated into synergistic therapy so that the sensitizer acts as a tracer for fluorescence/photoacoustic imaging, and the treatment process is visualized in a way that SDT combined with other therapies cannot achieve. This review summarizes the advanced sensitizers and the application of combination therapy, and explores the improvement strategies for promoting clinical transformation.
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Neoplasias , Fotoquimioterapia , Terapia por Ultrasonido , Humanos , Neoplasias/tratamiento farmacológico , Fototerapia , Terapia CombinadaRESUMEN
Retinal pericyte migration occurs in the early stage of diabetic retinopathy (DR), which is one of the important causes of pericyte loss. Autophagy has been found to play essential roles in the regulation of many types of cell migration. In this study, we explored the relationship between autophagy and retinal pericyte migration. In diabetic rats, the retinas became thinner, and the level of autophagy in each cell layer increased. In the primary culture of bovine retinal pericytes, we found that advanced glycation end products (AGEs) increased the migratory cell ability without influencing cell viability, which also increased the phosphorylation of focal adhesion kinase (FAK) and the expression of matrix metalloproteinase (MMP)-2 and decreased the expression of vinculin. AGEs-induced retinal pericyte autophagy and the inhibition of autophagy with chloroquine significantly inhibited cell migration, reversed AGEs-induced FAK phosphorylation, and changed vinculin and MMP-2 protein expression. These results provide a new insight into the migration mechanism of retinal pericytes. The early control of autophagy has a potential effect on regulating pericyte migration, which may contribute to keeping the integrity of retinal vessels in DR.
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Introduction: Acute pain is a prevalent problem for dementia residents in nursing homes. A variety of intervention strategies have been applied to address this problem. However, there remains an issue of inadequate pain control. This study aims to explore the analgesic efficacy of auricular acupressure (AA) for dementia residents with acute pain in nursing homes. Methods: A multicenter, single-blind, randomized, and sham-controlled clinical trial was performed in three nursing homes in Yinchuan, China. All of the 206 eligible patients with acute pain were randomly divided into two groups for real AA therapy or sham AA (at sham point stimulation) therapy. The primary outcome was measured with a face pain scale revised (FPS-R) score before the procedure, 5 min after the start of the intervention, and 5 min after finishing the procedure. Secondary outcomes covered three physiological parameters, adverse reactions observed, satisfaction level of caregivers, acceptance of patients, and additional use of analgesics. Results: There was a significant difference in pain scores based on FPS-R between the two groups (p < 0.01). Pain score in the true AA group was 1.84 ± 0.23, compared with 2.22 ± 0.81 in the sham AA group. No adverse events were found during the whole procedure for all patients. The satisfaction level of caregivers and acceptance of patients in the real AA group were significantly higher than those in the sham AA group. Conclusion: This study shows that real AA was an alternative analgesic modality in reducing acute pain in patients with mild dementia.
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BACKGROUND: Salvianolate, a common drug for stabilizing heart disease and Angina Pectoris, is considered to be off-label for preventing venous thromboembolism (VTE) or anticoagulation at present. However, many clinical studies have showed that salvianolate can effectively inhibit the deep-vein thrombosis (DVT) incidence, and prevent VTE of perioperative patients in the real world in China. OBJECTIVE: This analysis aimed to evaluate the effectiveness and safety of salvianolate in preventing VTE in perioperative patients. METHODS: Databases of PubMed, Cochrane Library, Embase, CNKI, Wanfang and VIP were searched until July 2019. Literature retrieval, data extraction and quality assessment were independently completed by two researchers and checked with each other. Review Manager 5.2 software was applied for meta-analysis. RESULTS: A total of 429 studies were retrieved, including 11 randomized controlled trials (RCTs) with a total of 1149 subjects. Compared with low molecular weight heparin (LMWH) group alone, salvianolate combined LMWH group had lower DVT incidence in preventing perioperative thrombosis (2.75% and 14.23%, OR: 0.21, 95% CI:[0.08,0.53]; Pâ=â.0009). The incidence of adverse reactions of experimental group was similar to that of control group (1.79% and 2.31%, OR: 0.65, 95% CI:[0.18,2.35]. Pâ=â.51). Compared with the control group, D-dimer level (D-D), platelet count (PLT), fibrinogen (FIB), whole blood high shear viscosity (WBHSV), and whole blood low shear viscosity (WBLSV) were all significantly decreased (Pâ<â.01), and prothrombin time (PT) was significantly increased (Pâ<â.05). CONCLUSION: Salvianolate combined LMWH has better effectiveness and the same safety in preventing venous thromboembolism in perioperative patients. However, due to the small number of included literatures, large sample studies are still needed to further verify this conclusion.
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Uso Fuera de lo Indicado , Extractos Vegetales/efectos adversos , Complicaciones Posoperatorias/epidemiología , Procedimientos Quirúrgicos Operativos/efectos adversos , Tromboembolia Venosa/epidemiología , China/epidemiología , Quimioterapia Combinada/efectos adversos , Quimioterapia Combinada/métodos , Heparina de Bajo-Peso-Molecular/administración & dosificación , Heparina de Bajo-Peso-Molecular/efectos adversos , Humanos , Periodo Perioperatorio/estadística & datos numéricos , Extractos Vegetales/administración & dosificación , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/prevención & control , Tiempo de Protrombina , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/etiología , Tromboembolia Venosa/prevención & controlRESUMEN
Sorafenib is a multikinase inhibitor capable of facilitating apoptosis, mitigating angiogenesis and suppressing tumor cell proliferation. In late-stage hepatocellular carcinoma (HCC), sorafenib is currently an effective first-line therapy. Unfortunately, the development of drug resistance to sorafenib is becoming increasingly common. This study aims to identify factors contributing to resistance and ways to mitigate resistance. Recent studies have shown that epigenetics, transport processes, regulated cell death, and the tumor microenvironment are involved in the development of sorafenib resistance in HCC and subsequent HCC progression. This study summarizes discoveries achieved recently in terms of the principles of sorafenib resistance and outlines approaches suitable for improving therapeutic outcomes for HCC patients.
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Carcinoma Hepatocelular/tratamiento farmacológico , Resistencia a Antineoplásicos/genética , Neoplasias Hepáticas/tratamiento farmacológico , Sorafenib/uso terapéutico , Apoptosis/efectos de los fármacos , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patología , Proliferación Celular/efectos de los fármacos , Resistencia a Antineoplásicos/efectos de los fármacos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Sorafenib/efectos adversos , Microambiente Tumoral/efectos de los fármacosRESUMEN
OBJECTIVES: To screen and identify ideal leading compounds from a drug library (ZINC15 database) with potential inhibition of aminopeptidase N(CD13) to contribute to medication design and development. RESULTS: Two novel natural compounds, ZINC000000895551 and ZINC000014820583, from the ZINC15 database were found to have a higher binding affinity and more favorable interaction energy binding with CD13 with less rodent carcinogenicity, Ames mutagenicity, and non-inhibition with cytochrome P-450 2D6. Molecular dynamics simulation analysis suggested that the 2 complexes, ZINC000000895551-CD13 and ZINC000014820583-CD13, have favorable potential energy, and exist stably in the natural circumstances. CONCLUSION: This study discovered that ZINC000000895551 and ZINC000014820583 were ideal leading compounds to be inhibitions targeting to CD13. These compounds were selected as safe drug candidates as CD13 target medication design and improvement. MATERIALS AND METHOD: Potential inhibitors of CD13 were identified using a series of computer-aided structural and chemical virtual screening techniques. Structure-based virtual screening was carried out to calculate LibDock scores, followed by analyzing their absorption, distribution, metabolism, and excretion and toxicity predictions. Molecule docking was employed to reveal binding affinity between the selected compounds and CD13. Molecular dynamics simulation was applied to evaluate stability of the ligand-CD13 complex under natural environment.
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Antígenos CD13/antagonistas & inhibidores , Sistemas de Liberación de Medicamentos/métodos , Descubrimiento de Drogas/métodos , Simulación de Dinámica Molecular , Antígenos CD13/química , Antígenos CD13/metabolismo , Bases de Datos Factuales , Evaluación Preclínica de Medicamentos/métodos , Humanos , Unión Proteica , Relación Estructura-ActividadRESUMEN
To maximize the utilization of Abaca lignin in the current biorefinery, structural characteristics of native lignin from Abaca were firstly comprehensively investigated. Parallelly, effective delignification of Abaca was achieved by alkaline hydrogen peroxide (AHP) process, which facilitated the production of specialty paper in industry. The structural changes of lignin macromolecules during the AHP delignification were illustrated by comparing the structural differences of the released lignin fraction and corresponding native lignin, which were analyzed via the advanced analytical methods, such as 2D-HSQC NMR, 31P NMR, pyrolysis-GC/MS, and GPC techniques. It was found that Abaca lignin is a HGS-type lignin, which is overwhelmingly composed of ß-O-4 linkages and abundant hydroxycinnamic acids (mainly p-coumaric acid). In addition, partial cleavage of ß-O-4 linkages and p-coumarate in lignin occurred during the AHP delignification process. Meanwhile, AHP process also led to the elevation of H-type lignin units in AHPL. Considering that ß-O-4 bond is vulnerable in the catalytic degradation process of lignin, the lignin with abundant ß-O-4 linkages is beneficial to the downstream conversion of lignin into aromatic chemicals.
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Peróxido de Hidrógeno/química , Lignina/química , Musa/química , Extractos Vegetales/química , Ácidos Cumáricos/química , Cromatografía de Gases y Espectrometría de Masas , Hidrólisis , Espectroscopía de Resonancia Magnética , Conformación Molecular , Relación Estructura-ActividadRESUMEN
Mastitis, a major disease affecting dairy cows, is most commonly caused by Staphylococcus aureus (S. aureus). Selenium (Se) can activate pivotal proteins in immune responses and regulate the immune system, and microRNA-155 (miR-155) is a key transcriptional regulator for inflammation-related diseases. We constructed the model of mouse mastitis in vivo and primary mouse mammary epithelial cells (MMECs) in vitro, which were induced by S. aureus. Se content of the mammary was estimated using an atomic fluorescence spectrophotometer. Histopathological analysis was performed via hematoxylin and eosin (H&E) staining. The mmu-miR-155-5p mimic was transfected in MMECs, and viability was determined through the MTT assay. Transfected efficiency was evaluated by qPCR and fluorescence staining. Cytokines including TNF-α, IL-1ß, IL-10 and TLRs were detected with qPCR. In addition, western blotting was used to evaluate the expression of the NF-κB and MAPKs signaling pathways. The results demonstrated that a Se-supplemented diet improved the content of Se in mammary tissues. Histopathological studies indicated that the mammary glands were protected in the Se-supplemented group after S. aureus infection. Se-supplementation suppressed the production of MPO, mmu-miR-155, TNF-α, IL-1ß, and TLR2 and significantly inhibited the phosphorylation of NF-κB and MAPKs in vivo and in vitro. All the data indicated that mmu-miR-155 played a pro-inflammatory role in our study, and Se-supplementation could suppress the expression of mmu-miR-155 to inhibit inflammation in S. aureus-induced mastitis in mice.
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Enfermedades de los Bovinos/tratamiento farmacológico , Mastitis/tratamiento farmacológico , MicroARNs/genética , Selenio/administración & dosificación , Infecciones Estafilocócicas/veterinaria , Animales , Bovinos , Enfermedades de los Bovinos/genética , Enfermedades de los Bovinos/inmunología , Enfermedades de los Bovinos/microbiología , Citocinas/genética , Citocinas/inmunología , Femenino , Regulación de la Expresión Génica , Mastitis/genética , Mastitis/inmunología , Mastitis/microbiología , Ratones , MicroARNs/inmunología , FN-kappa B/genética , FN-kappa B/inmunología , Infecciones Estafilocócicas/genética , Infecciones Estafilocócicas/inmunología , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/fisiología , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/inmunologíaRESUMEN
OBJECTIVE: To screen ideal lead compounds from a drug library (ZINC15 database) with potential inhibition effect against O6-methylguanine-DNA methyltransferase (MGMT) to contribute to medication design and refinement. METHODS: A series of computer-aided virtual screening techniques were used to identify potential inhibitors of MGMT. Structure-based virtual screening by LibDock was carried out to calculate LibDock scores, followed by absorption, distribution, metabolism, and excretion and toxicity predictions. Molecule docking was employed to demonstrate binding affinity and mechanism between the selected ligands and MGMT protein. Molecular dynamics simulation was performed to evaluate stability of the ligand-MGMT complex under natural circumstances. RESULTS: Two novel natural compounds, ZINC000008220033 and ZINC000001529323, from the ZINC15 database were found to bind with MGMT with a higher binding affinity together with more favorable interaction energy. Also, they were predicted to have less rodent carcinogenicity, Ames mutagenicity, and developmental toxicity potential as well as noninhibition with cytochrome P-450 2D6. Molecular dynamics simulation analysis demonstrated that the 2 complexes ZINC000008220033-MGMT and ZINC000001529323-MGMT had more favorable potential energy compared with reference ligand O6-benzylguanine, and they could exist stably in the natural environment. CONCLUSIONS: This study elucidated that ZINC000008220033 and ZINC000001529323 were ideal lead compounds with potential inhibition targeting to MGMT protein. These compounds were selected as safe drug candidates and may contribute a solid basis for MGMT target medication design and improvement.
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Sistemas de Liberación de Medicamentos/métodos , Descubrimiento de Drogas/métodos , Inhibidores Enzimáticos/farmacología , Simulación del Acoplamiento Molecular/métodos , O(6)-Metilguanina-ADN Metiltransferasa/antagonistas & inhibidores , Bases de Datos Factuales , Evaluación Preclínica de Medicamentos/métodos , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/metabolismo , Humanos , O(6)-Metilguanina-ADN Metiltransferasa/química , O(6)-Metilguanina-ADN Metiltransferasa/metabolismo , Estructura Secundaria de Proteína , Estructura Terciaria de ProteínaRESUMEN
Blaps rhynchopetera is a species of folk medicinal beetle that has been used for a long time in Southwest China. The complete mitogenome of the beetle (GenBank accession number MK854717) is 16,149 bp in size, including 13 protein-coding, 22 transfer RNAs, two ribosomal RNAs genes, and a noncoding D-loop region. The D-loop of 1255 bp length is located between rRNA-S and tRNAIle. The overall base composition of B. rhynchopetera is 41.58% for A, 10.31% for G, 31.77% for T, and 16.34% for C, with a high AT bias of 73.35%. The present data could contribute to detailed phylogeographic analysis of this valuable medicinal insect.
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Scoparone is a major biological active substance derived from the traditional Chinese herbal medicine called Artemisia capillaris. It has been confirmed that scoparone has anti-inflammatory, anti-tumor, hepatoprotective and antioxidant effects. However, the binding interaction of scoparone with bovine serum albumin (BSA) still remains unknown. Therefore, the present study was conducted to clarify the binding interaction of scoparone with BSA under simulated physiological conditions (pH = 7.4) by utilizing spectroscopic and molecular docking methods. The formation of the scoparone-BSA complex was identified by UV-vis absorption spectroscopy experiment results. The fluorescence experiment results revealed that the quenching mechanism was static quenching and the binding procedure was spontaneous mainly driven by hydrophobic interaction. At 310 K, the number of binding sites was approximately equal to 1 and the binding constant was 6.79 × 105 mol L-1. The binding distance (4.81 nm) between scoparone and BSA was determined by Förster's non-radiative energy transfer theory. Molecular docking and site marker competitive experiment results verified that scoparone was more likely to be located in site I of BSA. In addition, the results of synchronous fluorescence spectroscopy and circular dichroism spectroscopy experiments proved that scoparone slightly changed the conformation of BSA by binding interaction with BSA. These findings would be useful for understanding the pharmacokinetics of scoparone in vivo, including scoparone transport, distribution, metabolism and excretion.
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To evaluate the effect of Chinese medicine of invigorating spleen and kidney detoxification on simian immunodeficiency virus-infected rhesus macaque. Eight SIV rhesus macaques of the same age were randomly divided into Chinese medicine of invigorating spleen and kidney detoxification group(hereinafter referred to as Chinese medicine group) and anti-virus drug(HAART) group. The traditional Chinese medicine and antiviral therapy were given for 8 weeks, and peripheral blood was collected for detection in every 4 weeks. The results showed that Chinese medicine of invigorating spleen and kidney detoxification could not obviously decrease plasma viral load as HAART, but it can increase CD4 number in peripheral blood, especially the CD4 naive cells, and increase the number of CD4 and CD8 cells, enhance the immune response to pathogens. Therefore, it delayed the occurrence and development of spleen deficiency to a certain extent, indicating that the medicine had immune regulation effect, with considerable clinical value and application prospects.
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Medicamentos Herbarios Chinos/farmacología , Síndrome de Inmunodeficiencia Adquirida del Simio/tratamiento farmacológico , Animales , Terapia Antirretroviral Altamente Activa , Recuento de Linfocito CD4 , Macaca mulatta , Virus de la Inmunodeficiencia de los Simios , Carga ViralRESUMEN
Endometritis is commonly caused by pathogenic microorganisms, including Staphylococcus aureus (S. aureus). Piperine, which is a natural medicine, has shown a variety of biological activities. To explore the effect and mechanism of piperine on S. aureus endometritis, a mouse model of S. aureus endometritis was successfully established in the present study. Histopathological changes were observed with H&E staining, cytokines were analyzed by ELISA, mRNA was analyzed by qPCR, and proteins were detected by western blot. The results showed that piperine could significantly alleviate inflammatory injury in S. aureus endometritis. The qPCR and ELISA results showed that piperine effectively reduced the S. aureus-induced overexpression of TNF-α, IL-1ß, and IL-6 but increased the expression of IL-10. The S. aureus-induced inflammation was related to TLR-2 and TLR-4 because the results showed that their expression was increased in S. aureus infection but then decreased with piperine treatment. To further confirm that piperine caused an anti-inflammatory response by targeting NF-κB and MAPKs, the expression of I-κB, p65, p38, ERK, and JNK was measured. The phosphorylation of I-κB, p65, p38, ERK, and JNK was inhibited by piperine in a dose-dependent manner. All of the results indicated that piperine may be a potential anti-inflammatory drug both in endometritis and in other S. aureus-induced diseases.
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Selenium (Se), a nutritionally essential trace element, is associated with health and disease. Selenoprotein T (SelT) was identified as a redoxin protein with a selenocystein, localizing in the endoplasmic reticulum. The myosin light chain kinase (MLCK) and myosin light chain (MLC) play key roles in the contraction process of smooth muscle. The present study was to detect the effect and mechanism of SelT on the contraction process of gastric smooth muscle. The WT rats were fed with different Se concentration diets, and Se and Ca(2+) concentrations were detected in the gastric smooth muscle. Western blot and qPCR were performed to determine SelT, CaM, MLCK, and MLC expressions. MLCK activity was measured by identifying the rates of [γ-32P]ATP incorporated into the MLC. The results showed Se and Ca(2+) concentrations were enhanced with Se intake in gastric smooth muscle tissues. With increasing Se, SelT, CaM, MLCK and MLC expressions increased, and MLCK and MLC activation improved in gastric smooth muscle tissue. The SelT RNA interference experiments showed that Ca(2+) release, MLCK activation, and MLC phosphorylation were regulated by SelT. Se affected the gastric smooth muscle constriction by regulating Ca(2+) release, MLCK activation, and MLC phosphorylation through SelT. Se plays a major role in regulating the contraction processes of gastric smooth muscle with the SelT.
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Señalización del Calcio/efectos de los fármacos , Mucosa Gástrica/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Contracción Muscular/efectos de los fármacos , Músculo Liso/metabolismo , Quinasa de Cadena Ligera de Miosina/metabolismo , Selenio/farmacología , Selenoproteínas/biosíntesis , Animales , Activación Enzimática/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos BALB C , Cadenas Ligeras de Miosina/biosíntesis , Ratas , Ratas WistarRESUMEN
The first continuous cell line from the neonate larval tissues of Blaps rhynchoptera, which has been used as a folk medicine in Yunnan Province, China, was established and designated RIRI-BR1. This cell line was serially subcultured in Schneider's medium supplemented with 15% fetal bovine serum (FBS). The cells grew adherent to culture flasks and exhibited spindle-like and polygonal shapes. The growth rate was determined at the 50th passage, and the population doubling time was calculated to be 79.5 h. The post-thaw viability of the cell line at different passages showed that the cells from higher passages could be recovered easier after cryopreservation than the cells from lower passages. The average chromosome numbers from cells of the RIRI-BR1 cell line at passages 5 to 50 ranged from 12 to 130. The rDNA internal transcribed spacer (ITS) sequence analysis indicated that the RIRI-BR1 cell line was derived from B. rhynchoptera.
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Técnicas de Cultivo de Célula , Escarabajos/citología , Animales , Línea Celular , Supervivencia Celular , Cromosomas de Insectos , Escarabajos/genética , Criopreservación , Cariotipo , Larva/citologíaRESUMEN
BACKGROUND AND PURPOSE: Acute lung injury (ALI) is a severe illness with a high rate of mortality. Maresin 1 (MaR1) was recently reported to regulate inflammatory responses. We used a LPS-induced ALI model to determine whether MaR1 can mitigate lung injury. EXPERIMENTAL APPROACH: Male BALB/c mice were injected, intratracheally, with either LPS (3 mg·kg(-1) ) or normal saline (1.5 mL·kg(-1) ). After this, normal saline, a low dose of MaR1 (0.1 ng per mouse) or a high dose of MaR1 (1 ng per mouse) was given i.v. Lung injury was evaluated by detecting arterial blood gas, pathohistological examination, pulmonary oedema, inflammatory cell infiltration, inflammatory cytokines in the bronchoalveolar lavage fluid and neutrophil-platelet interactions. KEY RESULTS: The high dose of MaR1 significantly inhibited LPS-induced ALI by restoring oxygenation, attenuating pulmonary oedema and mitigating pathohistological changes. A combination of elisa and immunohistochemistry showed that high-dose MaR1 attenuated LPS-induced increases in pro-inflammatory cytokines (TNF-α, IL-1ß and IL-6), chemokines [keratinocyte chemokine, monocyte chemoattractant protein-5, macrophage inflammatory protein (MIP)-1α and MIP-1γ], pulmonary myeloperoxidase activity and neutrophil infiltration in the lung tissues. Consistent with these observations, flow cytometry and Western blotting indicated that MaR1 down-regulated LPS-induced neutrophil adhesions and suppressed the expression of intercellular adhesion molecule (ICAM)-1, P-selection and CD24. CONCLUSIONS AND IMPLICATIONS: High-dose MaR1 mitigated LPS-induced lung injury in mice by inhibiting neutrophil adhesions and decreasing the levels of pro-inflammatory cytokines.
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Lesión Pulmonar Aguda/tratamiento farmacológico , Ácidos Docosahexaenoicos/farmacología , Lipopolisacáridos/antagonistas & inhibidores , Lesión Pulmonar Aguda/inducido químicamente , Lesión Pulmonar Aguda/patología , Administración por Inhalación , Animales , Adhesión Celular/efectos de los fármacos , Ácidos Docosahexaenoicos/administración & dosificación , Mediadores de Inflamación/metabolismo , Lipopolisacáridos/administración & dosificación , Lipopolisacáridos/toxicidad , Masculino , Ratones , Ratones Endogámicos BALB C , Neutrófilos/efectos de los fármacos , Neutrófilos/patologíaRESUMEN
Optic neuritis is a common disease in young adults, inducing apoptosis of retinal ganglion cells, which leads to varying degree of visual function damages, even blindness. As the standard treatment, methylprednisolone pulse therapy can only promote the recovery of visual acuity but not prevent retinal ganglion cell degeneration. It cannot help improve the ultimate visual outcome. Both inflammatory response and endogenous oxidative stress play crucial roles in the progression of optic neuritis. The combination of immunomodulatory and antioxidant is expected to improve the prognosis of the disease by preventing the apoptosis of retinal ganglion cells. Triterpenoids (oleanolic acid derived) were reported to have the dual capacity of simultaneously repressing production of pro-inflammatory mediators and exerting neuroprotective effects through induction of anti-oxidant genes in experimental optic neuritis. Gypenosides with an aglycone mainly of dammarane-type tetracyclic triterpenoids, also has the dual capacity of immune regulation and antioxidation. Both gypenosides and oleanolic acid were reported to have similar roles in hepatoprotection. Beside, gypenosides were reported to have the capacity of modulating the activation of immune cells and the expression of cytokines. In addition, gypenosides showed neuroprotective effect against oxidative injury in dopaminergic neurons and mouse model of Parkinson's disease. Accordingly, we propose that gypenosides have potential neuroprotective and immunomodulatory effects on optic neuritis through antioxidation and immune regulation. The application of gypenosides might prevent the apoptosis of retinal ganglion cells and improve the ultimate visual outcome in patients with optic neuritis.
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Adyuvantes Inmunológicos/farmacología , Fármacos Neuroprotectores/farmacología , Neuritis Óptica/prevención & control , Animales , Gynostemma , Ratones , Ratones Endogámicos C57BL , Extractos Vegetales/farmacologíaRESUMEN
OBJECTIVE: To investigate the intervention effect of Danggui Shaoyao San on rats with cirrhotic ascites, and discuss the effect of arginine vasopressin (AVP) on cirrhotic ascites. METHOD: Male SD rats were randomly divided into the control group, the model group, Danggui Shaoyao San low, middle and high dose groups. The cirrhotic ascites rat model was established by CCl4 combined with phenobarbital. Their urines were collected at 24 h to observe urine excretion of each group. Filter papers were used to determine the amount of ascites. The levels of serum alanine aminotransferasa (ALT) , aspartate aminotransferase (AST) were detected by the automatic biochemistry analyzer. Plasma prothrombin time (PT) was evaluated by the blood coagulation analyzer. The concentration of AVP in plasma was detected by enzyme-linked immunosorbent assay (ELISA). Pathological changes in livers were observed by HE staining. RESULT: Compared with the model group, the Danggui Shaoyao San group showed significant improvement in live indexes, with notable decrease in serum ALT and AST and the time of PT, improvement in liver pathological changes. Simultaneously, the amount of ascites decreased to varying degrees, with notable increase in urine in 24 h and decrease in AVP concentration in plasma. CONCLUSION: Danggui Shaoyao San can notably improve liver functions of rats with cirrhotic ascites, reduce the generation of ascites and delay the progress of liver pathological changes. Its mechanism may be related to AVP.
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Ascitis/complicaciones , Ascitis/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Cirrosis Hepática/complicaciones , Animales , Arginina Vasopresina/sangre , Ascitis/sangre , Ascitis/fisiopatología , Medicamentos Herbarios Chinos/uso terapéutico , Hígado/efectos de los fármacos , Hígado/enzimología , Hígado/metabolismo , Hígado/fisiopatología , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: Interleukin-1ß-mediated production of matrix metalloproteinases (MMPs) plays a pivotal role in the process of osteoarthritis. Crocin, a pharmacologically active component of Crocus sativus L. (saffron), has been used in Chinese traditional medicine. In this study, we aimed to investigate the effects of crocin on MMP-1, MMP-3 and MMP-13 expression in rabbit chondrocytes induced by interleukin-1ß (IL-1ß) and in an experimental rabbit model induced by anterior cruciate ligament transection. METHODS: Chondrocytes isolated from the articular cartilage of 4-week-old rabbits were cultured and passaged. Confluent chondrocytes were treated with various concentrations of crocin in the presence or absence of IL-1ß (10 ng/ml) for 24 h. Quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting were used to investigate the expression of inducible MMP-1, MMP-3 and MMP-13. In addition, the in-vivo effects of crocin were assessed by morphological and histological analysis. RESULTS: IL-1ß markedly upregulated the expression of MMP-1, -3 and -13 in chondrocytes, and this activation was inhibited by co-incubation with crocin in a dose-dependent manner, in contrast with the control group. Moreover, crocin inhibited IL-1ß-induced activation of the nuclear factor kappa B pathway through suppressing degradation of inhibitory-kappa-B-α. In-vivo investigations showed that crocin ameliorated cartilage degeneration and that expression of the MMP-1, -3 and -13 genes in cartilage was significantly inhibited by crocin. CONCLUSION: Taken together, our findings suggest that the anti-inflammatory activity of crocin may be of potential value in the prevention and treatment of osteoarthritis.
Asunto(s)
Carotenoides/farmacología , Cartílago Articular/efectos de los fármacos , Condrocitos/efectos de los fármacos , Interleucina-1beta/farmacología , Osteoartritis/tratamiento farmacológico , Animales , Carotenoides/uso terapéutico , Cartílago Articular/metabolismo , Cartílago Articular/patología , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Femenino , Metaloproteinasas de la Matriz/biosíntesis , FN-kappa B/antagonistas & inhibidores , ConejosRESUMEN
<p><b>OBJECTIVE</b>To investigate the intervention effect of Danggui Shaoyao San on rats with cirrhotic ascites, and discuss the effect of arginine vasopressin (AVP) on cirrhotic ascites.</p><p><b>METHOD</b>Male SD rats were randomly divided into the control group, the model group, Danggui Shaoyao San low, middle and high dose groups. The cirrhotic ascites rat model was established by CCl4 combined with phenobarbital. Their urines were collected at 24 h to observe urine excretion of each group. Filter papers were used to determine the amount of ascites. The levels of serum alanine aminotransferasa (ALT) , aspartate aminotransferase (AST) were detected by the automatic biochemistry analyzer. Plasma prothrombin time (PT) was evaluated by the blood coagulation analyzer. The concentration of AVP in plasma was detected by enzyme-linked immunosorbent assay (ELISA). Pathological changes in livers were observed by HE staining.</p><p><b>RESULT</b>Compared with the model group, the Danggui Shaoyao San group showed significant improvement in live indexes, with notable decrease in serum ALT and AST and the time of PT, improvement in liver pathological changes. Simultaneously, the amount of ascites decreased to varying degrees, with notable increase in urine in 24 h and decrease in AVP concentration in plasma.</p><p><b>CONCLUSION</b>Danggui Shaoyao San can notably improve liver functions of rats with cirrhotic ascites, reduce the generation of ascites and delay the progress of liver pathological changes. Its mechanism may be related to AVP.</p>