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1.
Support Care Cancer ; 32(6): 370, 2024 May 22.
Artículo en Inglés | MEDLINE | ID: mdl-38776028

RESUMEN

OBJECTIVE: Immune checkpoint inhibitors (ICIs), specifically targeting the programmed cell death protein-1 or its ligand (PD-1/PD-L1), have been extensively used in the treatment of a spectrum of malignancies, although the predictive biomarkers remain to be elucidated. This study aims to investigate the association between baseline circulating levels of cytokines and the creatinine/cystatin C ratio (CCR) with the treatment outcomes of ICIs in patients with advanced cancer. METHODS: The pre-treatment circulating levels of 10 cytokines (PD-L1, CTLA4, CXCL10, LAG3, HGF, CCL2, MIG, GRANB, IL-18, and IL-6) were measured via automated capillary-based immunoassay platform in the serum of 65 advanced cancer patients treated with anti-PD-1/PD-L1-based systemic therapy and 10 healthy volunteers. The levels of cytokines and CCR were quantified and categorized into high and low groups based on the median value. The associations of serum cytokines and CCR with response to treatment, survival, and immune-related adverse events were assessed. RESULTS: Elevated circulating levels of 6 cytokines (PD-L1, CXCL10, HGF, CCL2, MIG, and IL-6) were observed in cancer patients compared with that in healthy volunteers. The correlation coefficients between cytokines, CCR and nutritional risk index were also calculated. In the cancer cohort (N = 65), low circulating HGF (P = 0.023, P = 0.029), low IL-6 (P = 0.002, P < 0.001), and high CCR (P = 0.031, P = 0.008) were associated with significantly improved progression-free survival (PFS) and overall survival (OS). Multi-variable COX analyses adjusted for clinicopathological factors revealed that low HGF, low IL-6, and high CCR were independent favorable prognostic factors for PFS (P = 0.028, P = 0.010, and P = 0.015, respectively) and OS (P = 0.043, P = 0.003, and P = 0.026, respectively). Grade 2 irAEs occurred more frequently in patients with low levels of circulating CCL2 and LAG3. CONCLUSIONS: Pre-treatment circulating levels of serum IL-6, HGF, and CCR may serve as independent predictive and prognostic biomarkers in advanced cancer patients treated with ICIs-based systemic therapy. These findings might help to identify potential patients who would benefit from these therapies.


Asunto(s)
Biomarcadores de Tumor , Creatinina , Citocinas , Inhibidores de Puntos de Control Inmunológico , Neoplasias , Humanos , Masculino , Femenino , Neoplasias/tratamiento farmacológico , Neoplasias/sangre , Persona de Mediana Edad , Anciano , Citocinas/sangre , Pronóstico , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Creatinina/sangre , Biomarcadores de Tumor/sangre , Adulto , Anciano de 80 o más Años , Antígeno B7-H1/sangre , Estudios de Casos y Controles
2.
World J Gastrointest Oncol ; 16(5): 2181-2199, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38764848

RESUMEN

BACKGROUND: Recent reviews have outlined the main nanomaterials used in relation to gastrointestinal tumors and described the basic properties of these materials. However, the research hotspots and trends in the application of nanomaterials in gastric cancer (GC) remain obscure. AIM: To demonstrate the knowledge structure and evolutionary trends of research into the application of nanomaterials in GC. METHODS: Publications related to the application of nanomaterials in GC were retrieved from the Web of Science Core Collection for this systematic review and bibliometric study. VOSviewer and CiteSpace were used for bibliometric and visualization analyses. RESULTS: From 2000 to 2022, the application of nanomaterials in GC developed rapidly. The keyword co-occurrence analysis showed that the related research topics were divided into three clusters: (1) The application of nanomaterials in GC treatment; (2) The application and toxicity of nanomaterials in GC diagnosis; and (3) The effects of nanomaterials on the biological behavior of GC cells. Complexes, silver nanoparticles, and green synthesis are the latest high-frequency keywords that represent promising future research directions. CONCLUSION: The application of nanomaterials in GC diagnosis and treatment and the mechanisms of their effects on GC cells have been major themes in this field over the past 23 years.

3.
Zhongguo Zhong Yao Za Zhi ; 48(7): 1751-1759, 2023 Apr.
Artículo en Chino | MEDLINE | ID: mdl-37282949

RESUMEN

Hepatic lipid deposition is one of the basic manifestations of obesity, and nowadays pharmacological treatment is the most important tool. Punicalagin(PU), a polyphenol derived from pomegranate peel, is a potential anti-obesity substance. In this study, 60 C57BL/6J mice were randomly divided into a normal group and a model group. After establishing a model of simple obesity with a high-fat diet for 12 weeks, the successfully established rat models of obesity were then regrouped into a model group, an orlistat group, a PU low-dose group, a PU medium-dose group, and a PU high-dose group. The normal group was kept on routine diet and other groups continued to feed the high-fat diet. The body weight and food intake were measured and recorded weekly. After 8 weeks, the levels of the four lipids in the serum of each group of mice were determined by an automatic biochemical instrument. Oral glucose tole-rance and intraperitoneal insulin sensitivity were tested. Hemoxylin-eosin(HE) staining was applied to observe the hepatic and adipose tissues. The mRNA expression levels of peroxisome proliferators-activated receptor γ(PPARγ) and C/EBPα were determined by real-time quantitative polymerase chain reaction(Q-PCR), and the mRNA and protein expression levels of adenosine 5'-monophosphate-activated protein kinase(AMPK), anterior cingulate cortex(ACC), and carnitine palmitoyltransferase 1A(CPT1A) were determined by Western blot. Finally, the body mass, Lee's index, serum total glyceride(TG), serum total cholesterol(TC), and low-density lipoprotein cholesterol(LDL-C) levels were significantly higher and high-density lipoprotein cholesterol(HDL-C) levels were significantly lower in the model group as compared with the normal group. The fat deposition in the liver was significantly increased. The mRNA expression levels of hepatic PPARγ and C/EBPα and the protein expression level of ACC were increased, while the mRNA and protein expression levels of CPT-1α(CPT1A) and AMPK were decreased. After PU treatment, the above indexes of obese mice were reversed. In conclusion, PU can decrease the body weight of obese mice and control their food intake. It also plays a role in the regulation of lipid metabolism and glycometabolism metabolism, which can significantly improve hepatic fat deposition. Mechanistically, PU may regulate liver lipid deposition in obese mice by down-regulating lipid synthesis and up-regulating lipolysis through activation of the AMPK/ACC pathway.


Asunto(s)
Proteínas Quinasas Activadas por AMP , PPAR gamma , Ratas , Ratones , Animales , Ratones Obesos , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , PPAR gamma/genética , PPAR gamma/metabolismo , Ratones Endogámicos C57BL , Hígado/metabolismo , Obesidad/tratamiento farmacológico , Obesidad/genética , Peso Corporal , Metabolismo de los Lípidos , Dieta Alta en Grasa/efectos adversos , Lípidos , Colesterol
4.
Zhongguo Zhong Yao Za Zhi ; 46(12): 3058-3065, 2021 Jun.
Artículo en Chino | MEDLINE | ID: mdl-34467696

RESUMEN

In this study, the compound search was completed through SciFinder and CNKI databases, and the drug-like properties were screened in FAFdrugs4 and SEA Search Server databases. In addition, based on the target sets related to acute myocardial ischemia(AMI) searched in disease target databases such as OMIM database, GeneCards database and DrugBank, a network diagram of chemical component-target-pathway-disease was established via Cytoscape to predict the potential active components of Corydalis Herba, a traditional Tibetan herbal medicine which derived from the aerial parts of Corydalis hendersonii and C. mucronifera against AMI. A protein-protein interaction(PPI) network was constructed through the STRING database and the core targets in the network were predicted. And the enrichment analyses of core targets were completed by DAVID database and R software. Furthermore, a molecular docking method was used to verify the binding of the components with core targets using softwares such as Autodock Vina. The present results showed that there were 60 compounds related to AMI in Corydalis Herba, involving 73 potential targets. The GO functional enrichment analysis obtained 282 biological processes(BP), 49 cell components(CC) and 78 molecular functions(MF). KEGG was enriched into 85 pathways, including alcoholism pathway, endocrine resistance pathway, calcium signaling pathway, cAMP signaling pathway, vascular endothelial growth factor signaling pathway and adrenergic signaling transduction pathway of myocardial cells. The results of network topology analysis showed that the key components of anti-AMI of Corydalis Herba might be tetrahydropalmatine, etrahydrocolumbamine, N-trans-feruloyloctopamine, N-cis-p-coumaroyloctopamine, N-trans-p-coumaroylnoradrenline and N-trans-p-coumaroyloctopamine, and their core targets might be CDH23, SCN4 B and NFASC. The results of molecular docking showed that the key components of Corydalis Herba had stable binding activity with the core targets. This study provides reference for further elucidation of the pharmacological effects of Corydalis Herba against AMI, subsequent clinical application, and development.


Asunto(s)
Corydalis , Medicamentos Herbarios Chinos , Isquemia Miocárdica , Medicamentos Herbarios Chinos/farmacología , Medicina Tradicional Tibetana , Simulación del Acoplamiento Molecular , Isquemia Miocárdica/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular
5.
Front Cell Dev Biol ; 9: 697539, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34262908

RESUMEN

BACKGROUND: Pathophysiological vascular remodeling in response to disturbed flow with low and oscillatory shear stress (OSS) plays important roles in atherosclerosis progression. Pomegranate extraction (PE) was reported having anti-atherogenic effects. However, whether it can exert a beneficial effect against disturbed flow-induced pathophysiological vascular remodeling to inhibit atherosclerosis remains unclear. The present study aims at investigating the anti-atherogenic effects of pomegranate peel polyphenols (PPP) extraction and its purified compound punicalagin (PU), as well as their protective effects on disturbed flow-induced vascular dysfunction and their underlying molecular mechanisms. METHODS: The anti-atherogenic effects of PPP/PU were examined on low-density lipoprotein receptor knockout mice fed with a high fat diet. The vaso-protective effects of PPP/PU were examined in rat aortas using myograph assay. A combination of in vivo experiments on rats and in vitro flow system with human endothelial cells (ECs) was used to investigate the pharmacological actions of PPP/PU on EC dysfunction induced by disturbed flow. In addition, the effects of PPP/PU on vascular smooth muscle cell (VSMC) dysfunction were also examined. RESULTS: PU is the effective component in PPP against atherosclerosis. PPP/PU evoked endothelium-dependent relaxation in rat aortas. PPP/PU inhibited the activation of Smad1/5 in the EC layers at post-stenotic regions of rat aortas exposed to disturbed flow with OSS. PPP/PU suppressed OSS-induced expression of cell cycle regulatory and pro-inflammatory genes in ECs. Moreover, PPP/PU inhibited inflammation-induced VSMC dysfunction. CONCLUSION: PPP/PU protect against OSS-induced vascular remodeling through inhibiting force-specific activation of Smad1/5 in ECs and this mechanism contributes to their anti-atherogenic effects.

6.
Zhongguo Zhong Yao Za Zhi ; 45(12): 2817-2826, 2020 Jun.
Artículo en Chino | MEDLINE | ID: mdl-32627455

RESUMEN

Zerumbone(ZER), one of humulane-type sesquiterpenoids, showed its unique advantage against tumor activities. The main underlying mechanisms include inhibiting the growth and proliferation of cancer cells, inducing apoptosis of cancer cells and differentiation of cancer cells, regulating immune function, inhibiting invasion and metastasis of cancer cells, and reversing multidrug resistance of cancer cells. Studies on ZER focusing its cytotoxic or anti-tumor is one of hot topic. Currently, with the increasing studies on ZER, the clarified mechanisms are getting rich. The present paper describes a summary of its anti-tumor mechanism of action and helps to provide significant reference to more in-depth research.


Asunto(s)
Antineoplásicos/farmacología , Sesquiterpenos/farmacología , Apoptosis/efectos de los fármacos , Línea Celular Tumoral
7.
Zhongguo Zhong Yao Za Zhi ; 45(9): 2063-2072, 2020 May.
Artículo en Chino | MEDLINE | ID: mdl-32495555

RESUMEN

Bawei Chenxiang Powder is a traditional Tibetan folk medicine formula, consisting of resinous wood of Aquilaria sinensis, kernel of Myristica fragrans, fruit of Choerospondias axillaris, travertine, resin of Boswellia carterii or B. bhaw-dajiana, stem of Aucklandia lappa, fruit of Terminalia chebula(roasted), and flower of Gossampinus malabarica. It has the function of clearing heart heat, nourishing heart, tranquilizing mind, and inducing resuscitation, which has been used for the treatment of coronary heart disease and angina pectoris. Modern research shows that the medicine materials of this formula mainly contain terpenoids like sesquiterpenes and triterpenes and polyphenols like flavonoids, lignans, and tannins, displaying some pharmacological activities such as anti-myocardial ischemia, anti-cerebral ischemia, and spatial learning and memory promotion. This review summaries the traditional uses, chemical constituents, and pharmacological activities research progress, hopefully to provide a reference for clarification of its pharmacological active ingredients.


Asunto(s)
Medicamentos Herbarios Chinos , Terminalia , Flavonoides , Medicina Tradicional Tibetana , Tibet
8.
Cardiovasc Drugs Ther ; 34(1): 3-14, 2020 02.
Artículo en Inglés | MEDLINE | ID: mdl-32103377

RESUMEN

PURPOSE: We investigated whether increased expression of activated mitogen-activated protein kinase (MAPK) kinases 1 (MEK1) restores ischemic post-conditioning (IPostC) protection in hypertrophic myocardium following ischemia/reperfusion (I/R) injury. METHODS: C57Bl/6 mice received recombinant adeno-associated virus type 9 (rAAV9)-mediated activated MEK1 gene delivery systemically, then following the induction of cardiac hypertrophy via transverse aortic constriction for 4 weeks. In a Langendorff model, hypertrophic hearts were subjected to 40 min/60 min I/R or with IPostC intervention consisting of 6 cycles of 10 s reperfusion and 10 s no-flow before a 60-min reperfusion. Hemodynamics, infarct size (IS), myocyte apoptosis and changes in expression of reperfusion injury salvage kinase (RISK) pathway were examined. RESULTS: rAAV9-MEK1 gene delivery led to a 4.3-fold and 2.7-fold increase in MEK1 mRNA and protein expression in the heart versus their control values. I/R resulted in a larger IS in hypertrophic than in non-hypertrophic hearts (52.3 ± 4.7% vs. 40.0 ± 2.5%, P < 0.05). IPostC mediated IS reduction in non-hypertrophic hearts (27.6 ± 2.6%, P < 0.05), while it had no significant effect in hypertrophic hearts (46.5 ± 3.1%, P=NS) compared with the IS in non-hypertrophic or hypertrophic hearts subjected to I/R injury only, respectively. Hemodynamic decline induced by I/R was preserved by IPostC in non-hypertrophic hearts but not in hypertrophic hearts. rAAV9-MEK1 gene delivery restored IPostC protection in hypertrophic hearts evidenced by reduced IS (32.0 ± 2.8% vs. 46.5 ± 3.1%) and cardiac cell apoptosis and largely preserved hemodynamic parameters. These protective effects were associated with significantly increased phosphorylation of ERK1/2 and ribosomal protein S6 kinases (p70S6K), but it had no influence on Akt and glycogen synthase kinase-3ß. CONCLUSION: These results demonstrated that rAAV9-mediated activated MEK1 expression restores IPostC protection in the hypertrophic heart against I/R injury through the activation of ERK pathway.


Asunto(s)
Dependovirus/genética , Técnicas de Transferencia de Gen , Vectores Genéticos , Hipertrofia Ventricular Izquierda/terapia , Poscondicionamiento Isquémico , MAP Quinasa Quinasa 1/biosíntesis , Infarto del Miocardio/prevención & control , Daño por Reperfusión Miocárdica/prevención & control , Miocardio/enzimología , Animales , Apoptosis , Modelos Animales de Enfermedad , Inducción Enzimática , Hipertrofia Ventricular Izquierda/enzimología , Hipertrofia Ventricular Izquierda/genética , Hipertrofia Ventricular Izquierda/patología , Preparación de Corazón Aislado , MAP Quinasa Quinasa 1/genética , Masculino , Ratones Endogámicos C57BL , Proteína Quinasa 1 Activada por Mitógenos/metabolismo , Proteína Quinasa 3 Activada por Mitógenos/metabolismo , Infarto del Miocardio/enzimología , Infarto del Miocardio/genética , Infarto del Miocardio/patología , Daño por Reperfusión Miocárdica/enzimología , Daño por Reperfusión Miocárdica/genética , Daño por Reperfusión Miocárdica/patología , Miocardio/patología , Fosforilación , Proteínas Quinasas S6 Ribosómicas 70-kDa/metabolismo
9.
Zhongguo Zhong Yao Za Zhi ; 45(24): 5917-5928, 2020 Dec.
Artículo en Chino | MEDLINE | ID: mdl-33496131

RESUMEN

Saussurea lappa originates in India, and now mainly grow in Yunnan, Sichuan and other places in China. It is one of the commonly used traditional herbal medicines in Tibet and other minority regions, with effects in regulating qi to relieve pain and invigo-rating spleen to promote food. It has been used in clinic for gastrointestinal diseases, such as Qi stagnation syndrome of spleen and stomach, diarrhea and tenesmus. More than 200 compounds have been identified from S. lappa. Among them, sesquiterpenoids attracted much attention. In terms of the number of compounds, eudesmanetype is dominant, guaiane and germacranetypes have also been reported frequently. Pharmacological studies have involved extracts, volatile oils and monomeric components represented by dehydrocostus lactone. Anti-tumor, anti-inflammatory and anti-bacterial effects on digestive system have attracted great attention. However, due to the complex sources of S. lappa and widely used in clinical practice, there is few research progress on relevant chemical constituents and pharmacological activities. This paper systematically summarizes terpenes and the pharmacological effects of S. lappa, in order to provide basis for further studies and clinical applications.


Asunto(s)
Saussurea , Sesquiterpenos , China , Extractos Vegetales , Terpenos , Tibet
10.
Zhongguo Zhong Yao Za Zhi ; 42(19): 3676-3683, 2017 Oct.
Artículo en Chino | MEDLINE | ID: mdl-29235279

RESUMEN

Meconopsis horridula is one of alpine plants belonging to family Papaveraceae, mainly distributed in Himalaya Range area. M. horridula is a rare alpine flower, and is a kind of traditional Tibetan medicine, which has been included in more than 40 compound formulae, having efficacies of clearing away heat and alleviating pain, activating blood circulation to remove stasis, traditionally used for the treatment of fractures, injuries, and chest and back pains. Modern research shows that the whole plant of M. horridula contains alkaloids, flavonoids, and terpenes, and its pharmacological activities including antitumor, antivirus and myocardial protection etc. However, due to various factors, the current research of M.horridula still faces many challenges. This paper summaries herein a progress of MH on its ecological resources, traditional uses, and studies on chemical constituents and pharmacological effects, hopefully to provide a useful reference for the ecological protection and applications.


Asunto(s)
Alcaloides/farmacología , Flavonoides/farmacología , Medicina Tradicional Tibetana , Papaveraceae/química , Fitoquímicos/farmacología , Terpenos/farmacología
11.
Colloids Surf B Biointerfaces ; 159: 580-585, 2017 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-28854414

RESUMEN

Based on the structurally similar properties of progesterone and cholesterol, chitosan-coated cholesterol-free liposomes (CS-Lipo/Prog) were formulated. CS-Lipo/Prog are spherical and uniform in size (662.1±19.3nm) with positive potential (28.19±1.97mV). The average drug entrapment efficiency (EE) is approximately 80%. The in vitro release profile of CS-Lipo/Prog shows sustained release. The in vitro stability evaluation demonstrated that CS-Lipo/Prog can efficiently shield Prog from degradation in the gastrointestinal tract. CS-Lipo/Prog showed a longer MRT and higher AUC0-infinite after oral administration to mice than in the control group (progesterone-free). The relative bioavailability of CS-Lipo/Prog was higher than that of progesterone soft capsules (QINING®) and Lipo/Prog. Collectively, these findings suggest that cholesterol-free chitosan-coated liposomes are a promising alternative for improving the oral bioavailability of progesterone.


Asunto(s)
Quitosano/química , Colesterol/química , Liposomas/química , Progesterona/química , Animales , Tracto Gastrointestinal/metabolismo , Ratones
12.
Biochim Biophys Acta ; 1864(1): 20-8, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26472331

RESUMEN

SRM (selected reaction monitoring), a tandem mass spectrometry-based method characterized by high repeatability and accuracy, is an effective tool for the quantification of predetermined proteins. In this study, we built a time-scheduled dimethyl-SRM method that can provide the precise relative quantification of 92 proteins in one run. By applying this method to the Salmonella PhoP/PhoQ two-component system, we found that the expression of selected PhoP/PhoQ-activated proteins in response to Mg(2+) concentrations could be divided into two distinct patterns. For the time-course SRM experiment, we found that the dynamics of the selected PhoP/PhoQ-activated proteins could be divided into three distinct patterns, providing a new clue regarding PhoP/PhoQ activation and regulation. Moreover, the results for iron homeostasis proteins in response to Mg(2+) concentrations revealed that the PhoP/PhoQ two-component system may serve as a repressor for iron uptake proteins. And ribosomal protein levels clearly showed a response to different Mg(2+) concentrations and to time.


Asunto(s)
Proteínas Bacterianas/metabolismo , Biología Computacional/métodos , Proteómica/métodos , Salmonella/metabolismo , Espectrometría de Masas en Tándem/métodos , Western Blotting , Relación Dosis-Respuesta a Droga , Magnesio/farmacología , Péptidos/metabolismo , Mapas de Interacción de Proteínas/efectos de los fármacos , Proteoma/metabolismo , Factores de Tiempo
13.
Chem Biodivers ; 12(10): 1443-65, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-26460554
14.
Zhongguo Zhong Yao Za Zhi ; 39(5): 769-76, 2014 Mar.
Artículo en Chino | MEDLINE | ID: mdl-25204163

RESUMEN

Litsea cubeba is one of aromatic medicinal plant belonging to family Lauraceae. The roots, stems and fruits of L. cubeba have been widely applied as folk medicines in some districts in China for relieving rheumatism and cold, regulating Qi (meridian) to alleviate pain. Previous studies revealed that this species contains major alkaloids, in specific aporphines, and minor flavonoids, lignans as well. Related pharmacological investigations demonstrated its activities and clinical applications on cardiovascular diseases, anti-cancer, against rheumatoid arthritis, relieving asthma and anti-allergic effects, as anti-oxidants, and so on. As an effort for further exploration of this bioactive ingredients and potential drug development, this paper summarizes most phytochemical and pharmacological results. Further, future prospects are also included.


Asunto(s)
Litsea/química , Extractos Vegetales/química , Extractos Vegetales/farmacología , Plantas Medicinales/química , Animales , Quimioterapia , Humanos , Estructura Molecular
15.
Urolithiasis ; 42(5): 409-14, 2014 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-25092435

RESUMEN

The actual preventive and therapeutic effects of alkalinizing urine on melamine-induced bladder stones (cystolith) are not completely known. Using an ideal model, two experiments were conducted in Balb/c mice. The mice were fed a normal diet in controls and a melamine diet in the other groups. The first day was set as experiment-day 1. In "Experiment 1", either low-/mid-/high-dose sodium bicarbonate (SB) or sterile water was administered by intragastric perfusion (once daily) to the mice for 14 days. Relative to the model group, the mean pH of the urine in the SB groups was significantly elevated at 3 h after SB administration, with a significant decrease in cystolith incidence on experiment-day 14. In "Experiment 2", on experiment-day 12, the melamine diet was replaced by a normal diet in 4 groups with melamine withdrawal (MW). Meanwhile, either mid-/high-dose SB or sterile water was administered by intragastric perfusion (once) to the mice in the corresponding groups. On experiment-day 12, after an additional 8 h, the cystolith incidence was significantly reduced in the high-SB, MW + mid-SB and MW + high-SB groups than in the model group. In conclusion, low urinary pH is one of the main determinants of the formation of melamine-associated stones, urinary alkalinization can be achieved by a proper dose of oral SB, and SB acts to prevent and treat melamine-induced cystoliths in mice.


Asunto(s)
Bicarbonato de Sodio/uso terapéutico , Cálculos de la Vejiga Urinaria/tratamiento farmacológico , Cálculos de la Vejiga Urinaria/prevención & control , Animales , Femenino , Concentración de Iones de Hidrógeno , Masculino , Ratones , Ratones Endogámicos BALB C , Triazinas/administración & dosificación , Cálculos de la Vejiga Urinaria/inducido químicamente , Cálculos de la Vejiga Urinaria/orina
16.
Exp Lung Res ; 39(10): 441-52, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24245991

RESUMEN

Seawater drowning can lead to acute lung injury (ALI). However, the molecular and cellular mechanisms underlying this phenomenon remain elusive. The overall aim of this study is to clarify the role of autophagy in seawater-induced ALI, by which we can further understand the molecular mechanism and develop new methods for prevention and treatment of seawater-induced ALI. In this study, electron microscopy, western blot analysis, and RT-PCR were used to detect autophagy in lung tissues. Moreover, arterial blood gas analysis, lung weight coefficient, TNF-α, IL-8 in bronchoalveolar fluid (BALF), histopathology were used to detect the lung injury of seawater exposure. An inhibitor of autophagy (3-Methyladenine, 3-MA) was injected intraperitoneally before seawater exposure to further explore the role of autophagy in ALI. Electron microscopy revealed increasing autophagosomes in alveolar epithelial cell in seawater group compared with the control. The transcription and expression levels (mRNA and protein levels) of the LC3 II significantly increased in lung tissue of seawater group compared with those in control group. Furthermore, the alterations of autophage were basically consistent with the changes in arterial blood gas, lung weight coefficient, TNF-α, IL-8 in BALF and morphologic findings. In addition, inhibition of autophagy by 3-MA partly ameliorated seawater-induced ALI, as indicated by reduced lung weight coefficient and TNF-α in BALF, as well as increased PaO2. In conclusion, seawater aspiration triggered autophagy, and autophagy may be a scathing factor responsible for ALI induced by seawater.


Asunto(s)
Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/patología , Autofagia , Agua de Mar/efectos adversos , Lesión Pulmonar Aguda/metabolismo , Adenina/análogos & derivados , Adenina/farmacología , Animales , Autofagia/efectos de los fármacos , Modelos Animales de Enfermedad , Interleucina-8/metabolismo , Masculino , Microscopía Electrónica de Transmisión , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Ahogamiento Inminente/complicaciones , Ahogamiento Inminente/patología , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Aspiración Respiratoria/complicaciones , Aspiración Respiratoria/metabolismo , Aspiración Respiratoria/patología , Factor de Necrosis Tumoral alfa/metabolismo
17.
Food Chem Toxicol ; 50(7): 2318-24, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22579608

RESUMEN

The natural outcome of melamine-induced bladder stones (cystoliths) with bladder epithelial hyperplasia (BEH) after melamine withdrawn is unclear. Using an ideal dual-model system, three experiments were conducted in BALB/c mice. Each experiment included a control, model 1 and model 2 groups. The mice were fed a regular diet in controls or a 9373 ppm melamine diet in models, and the first day was designated as dosing day 1. The melamine diet was then replaced by the regular diet in the model 2 groups, and the first day was designated as post-dosing day 1. On dosing days 12, 35 and 49, the incidence of cystoliths and diffusely active BEH was 8/8 in the mice of three model 1 groups. On post-dosing days 1, 4 and 8, in the mice of three model 2 groups, the incidence of cystoliths was 2/8, 0/8 and 1/8, respectively, and the progressive regression of BEH was observed. In conclusion, both the stones and BEH have the natural property of rapid development and rapid regression, and melamine withdrawn plays a key role in the stone dissolution-discharge necessary for BEH regression. BEH may be reversible after the discharge of the stones. The conventionally conservative therapy is thus reasonable.


Asunto(s)
Triazinas/toxicidad , Cálculos de la Vejiga Urinaria/inducido químicamente , Urotelio/efectos de los fármacos , Animales , Hiperplasia , Ratones , Ratones Endogámicos BALB C , Cálculos de la Vejiga Urinaria/patología , Urotelio/patología
18.
Food Chem Toxicol ; 49(12): 3013-7, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-21930179

RESUMEN

The key to establishing a standardized melamine-induced animal bladder stone (cystolith) model is to determine the most appropriate daily dose of dietary melamine, which is unknown. Based on golden section theory that is a well-known preferred proportion (0.618), and the 50% lethal dose (LD50) of mouse oral melamine [4550 mg/kg body weight (bw)], we proposed that the daily dose may be close to the LD50's golden section (i.e., 0.618 × 4550 mg melamine/kg bw). The latter as an average daily dose corresponds to 9373 ppm melamine diet in mice. In repeated experiments, a 100% incidence of cystoliths was observed on modeling day 14 in Balb/c and C57BL/6 mice fed the diet but not in mice fed similar diets containing 9842 (i.e., 9373 × 105%) or 8904 (i.e., 9373 × 95%) ppm melamine; the stones were relatively uniform and the difference in stone incidences between sexes or ages was not found in each 9373 ppm melamine group. In conclusion, 9373 ppm melamine diet is at least near the optimal dose diet or ideal for the rapid and stable establishment of a standardized cystolith model in the mice, and dietary melamine dose neither sex nor age is critical for stone formation.


Asunto(s)
Dieta/normas , Triazinas/toxicidad , Cálculos de la Vejiga Urinaria/patología , Administración Oral , Animales , Peso Corporal , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Femenino , Dosificación Letal Mediana , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Cálculos de la Vejiga Urinaria/inducido químicamente
19.
Zhongguo Gu Shang ; 22(11): 848-51, 2009 Nov.
Artículo en Chino | MEDLINE | ID: mdl-20084945

RESUMEN

OBJECTIVE: To investigate the role of anti-inflammatory effect and it's mechansim of Qufeng Zhitong capsule on the collagen-induced arthritis rat through the study of arthritis, joint inflammation and joint erosions. METHODS: Fifty male SD rat were assigned to 5 groups: normal control group, arthritis model group, and Qufeng Zhitong capsule treatment group (including low, medium and high doses), each group contains 10 rats. Arthritis were induced by immunization with type II collagen (CII) in complete Freund's adjuvant (CFA). After administered Qufeng Zhitong capsule 2 weeks, the volume of back foot of arthritis rat were detected, and the histology changes of the ankle joints of the arthritis rat were studied. The serum levels of IL-10 and TNF-alpha were measured by ELISA. RESULTS: After treated with Qufeng Zhitong capsule, the swelling of the paw of the rats were significantly decreased compared with the controls. Histology study demonstrated that the Qufeng Zhitong capsule treatment could reduce the synovium hyperplasia and inflammatory cell infiltration, the inhibitory effects were in accordance with the doses of the drug. The serum levels of pro-inflammatory cytokine of TNF-alpha in the arthritis rat were not changed significantly, while the serum levels of anti-inflammatory cytokine of IL-10 were elevated significantly after treated with Qufeng Zhitong capsule. CONCLUSION: Qufeng Zhitong capsule can inhibit the synovium hyperplasia and cartilage erosion by stimulating the serum levels of anti-inflammatory cytokine of IL-10 and suggest it can be a candidate of treatment of rheumatoid arthritis.


Asunto(s)
Antiinflamatorios/farmacología , Artritis Experimental/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Animales , Articulación del Tobillo/efectos de los fármacos , Articulación del Tobillo/patología , Antiinflamatorios/uso terapéutico , Artritis Experimental/sangre , Artritis Experimental/patología , Cápsulas , Proliferación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/uso terapéutico , Interleucina-10/sangre , Masculino , Ratas , Ratas Sprague-Dawley , Membrana Sinovial/efectos de los fármacos , Membrana Sinovial/patología , Factor de Necrosis Tumoral alfa/sangre
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