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Nonalcoholic fatty liver disease (NAFLD) is regarded as the most common liver disease with no approved therapeutic drug currently. Silymarin, an extract from the seeds of Silybum marianum, has been used for centuries for the treatment of various liver diseases. Although the hepatoprotective effect of silybin against NAFLD is widely accepted, the underlying mechanism and therapeutic target remain unclear. In this study, NAFLD mice caused by methionine-choline deficient (MCD) diet were orally administrated with silybin to explore the possible mechanism and target. To clarify the contribution of peroxisome proliferator-activated receptor α (PPARα), PPARα antagonist GW6471 was co-administrated with silybin to NAFLD mice. Since silybin was proven as a PPARα partial agonist, the combined effect of silybin with PPARα agonist, fenofibrate, was then evaluated in NAFLD mice. Serum and liver samples were collected to analyze the pharmacological efficacy and expression of PPARα and its targets. As expected, silybin significantly protected mice from MCD-induced NAFLD. Furthermore, silybin reduced lipid accumulation via activating PPARα, inducing the expression of liver cytosolic fatty acid-binding protein, carnitine palmitoyltransferase (Cpt)-1a, Cpt-2, medium chain acyl-CoA dehydrogenase and stearoyl-CoA desaturase-1, and suppressing fatty acid synthase and acetyl-CoA carboxylase α. GW6471 abolished the effect of silybin on PPARα signal and hepatoprotective effect against NAFLD. Moreover, as a partial agonist for PPARα, silybin impaired the powerful lipid-lowering effect of fenofibrate when used together. Taken together, silybin protected mice against NAFLD via activating PPARα to diminish lipid accumulation and it is not suggested to simultaneously take silybin and classical PPARα agonists for NAFLD therapy.
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OBJECTIVE@#To investigate the protective effect of Zengye Decoction (, ZYD) on the submandibular glands (SMGs) in nonobese diabetic (NOD) mice.@*METHODS@#Twenty-seven female NOD mice were randomly equally divided into 3 groups: the model group, the hydroxychloroquine (HCQ) group, and the ZYD group. Nine C57/B6 mice served as the normal group. After 1-week acclimation, the HCQ and ZYD groups were intragastrically administered with HCQ and ZYD, respectively, and the normal and model groups were administered with normal saline. Changes in the salivary flow rate were observed. Mice from all 4 groups were sacrificed at the age of 20 weeks. The serum and SMGs were collected. Serum cytokines gamma-interferon (IFN-γ), interleukin-10 (IL-10) were detected by enzyme-linked immunosorbent assay. Histological changes in the submandibular glands were examined by hematoxylin and eosin staining. The mRNA expression of IFN-γ, IL-10 and vasoactive intestinal peptide (VIP) in the submandibular glands were measured by real-time polymerase chain reaction.@*RESULTS@#Compared with the model group, the salivary flow of the ZYD group significantly increased (P<0.05), the extent of the histological changes was ameliorated (P<0.05), and the Th1/Th2 cytokine imbalance was remedied (P<0.05). In the ZYD-treated mice, the VIP mRNA was up-regulated (P<0.05).@*CONCLUSIONS@#ZYD is beneficial in protecting structure and function of SMGs in NOD mice. The mechanism may be associated with the correction of the Th1/Th2 cytokine imbalance, and with the prevention of a progressive decline of the VIP level.
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Animales , Femenino , Ratones , Citocinas , Sangre , Medicamentos Herbarios Chinos , Farmacología , Ratones Endogámicos C57BL , Ratones Endogámicos NOD , Salivación , Síndrome de Sjögren , Quimioterapia , Alergia e Inmunología , Glándula Submandibular , Patología , Células TH1 , Alergia e Inmunología , Células Th2 , Alergia e Inmunología , Péptido Intestinal Vasoactivo , GenéticaRESUMEN
Sjögren's syndrome is a chronic autoimmune disease with unclear etiology. From the point of etiology, Chinese medicine (CM) theory holds that pathological products like dry toxin, blood stasis are produced in the pathological process. They are both pathologic results and pathogenic factors for its further development. So pathological products are also named as second pathogenic factors. In this article, the concept of second pathogenic factors was sorted and defined. Main second pathogenic factors of Sjögren's syndrome were pinpointed, and their modern medical bases were analyzed. Authors came to a conclusion that clearing away second pathogenic factors is a key point in treating Sjögren's syndrome.
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Humanos , Síndrome de Sjögren , PatologíaRESUMEN
AIM@#This study was designed to explore the effects of short-term and long-term pretreatment of diammonium glycyrrhizinate (GLN) on the pharmacokinetics of entecavir (ETV) in rats.@*METHODS@#Male SD rats were randomized into short-term and long-term experimental groups, respectively. In the short-term experiment, the control group received saline, the low dose group received GLN 13.5 mg·kg(-1) and the high dose group received GLN 40.5 mg·kg(-1). ETV (0.09 mg·kg(-1)) was given i.g. 0.5 h after saline/GLN administration. For the long-term experiment, rats were allocated into two experimental designs. The control group received saline/ETV (0.09 mg·kg(-1)), the low dose group received GLN 13.5 mg·kg(-1)/ETV 0.09 mg·kg(-1) + GLN 13.5 mg·kg(-1), while the high dose group received GLN 40.5 mg·kg(-1)/ETV 0.09 mg·kg(-1) + GLN 40.5 mg·kg(-1); all administration was continued for 15 days. On the 16(th) day, 0.09 mg·kg(-1) ETV was administrated to all groups. Blood samples were obtained at different time points after ETV administration to determine plasma ETV concentrations.@*RESULTS@#Pretreatment with glycyrrhizin resulted in no significant alterations in the main pharmacokinetic parameters of ETV in the short-term and long-term administration experiments.@*CONCLUSION@#Diammonium glycyrrhizinate has no effect on ETV pharmacokinetics in rats.
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Animales , Masculino , Ratas , Interacciones Farmacológicas , Ácido Glicirrínico , Farmacología , Guanina , Sangre , Farmacocinética , Ratas Sprague-DawleyRESUMEN
<p><b>BACKGROUND</b>Seroma formation is one of the most common complications after breast cancer surgery. Various risk factors have been evaluated for their associations with the development of seromas in Western populations. However, similar data are not available in Chinese series. Therefore, we sought to investigate the potential risk factors for Chinese breast cancer patients.</p><p><b>METHODS</b>A prospective study of female breast cancer patients undergoing surgery was carried out in Cancer Hospital of Fudan University, Shanghai, China. Univariate analyses were performed by chi-square test or Student's t test or Mann-Whitney test and multivariate analyses by stepwise Logistic regression. The logistic model included age (years), total serum protein concentration (g/L), drainage volume on postoperative day 3 (POD 3; ml) and time to daily drainage volume not more than 30 ml (TTV30; days).</p><p><b>RESULTS</b>A total of 158 patients with breast cancer were studied. The mean age at diagnosis was (52.14 ± 10.77) years (range 25 - 92). During the follow-up period, 24 (15.2%) patients developed seromas. Calculated as continuous variables in the stepwise Logistic regression, age (OR = 1.090, 95%CI 1.028 - 1.155, P = 0.004), total serum protein concentration (OR = 0.886, 95%CI 0.791 - 0.992, P = 0.036), drainage volume on POD3 (OR = 1.013, 95%CI 1.002 - 1.023, P = 0.017) and TTV30 (OR = 1.273, 95%CI 1.039 - 1.561, P = 0.020) were independent risk factors for seroma formation. Additionally, significant difference in daily drainage volume was substantiated in the analysis by seroma formation (P = 0.034) rather than by type of surgery (P = 0.713).</p><p><b>CONCLUSIONS</b>Although the pathogenesis of seroma remains controversial, such risk factors as age, nutritional status, drainage volume on POD3 and TTV30 should be considered for prediction and prevention of seroma formation in Chinese breast cancer patients.</p>
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Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Persona de Mediana Edad , Pueblo Asiatico , Neoplasias de la Mama , Cirugía General , Complicaciones Posoperatorias , Estudios Prospectivos , Factores de Riesgo , SeromaRESUMEN
<p><b>OBJECTIVE</b>To evaluate the genotoxicity of a magnesium alloy coated with beta-tricalcium phosphate (beta-TCP).</p><p><b>METHODS</b>Four groups were designed. In the first group, AZ31B magnesium alloy surface was coated with beta-TCP using chemical bath deposition, and in the second group magnesium alloy was tested. The other two groups were negative control (pure titanium) and positive control groups (0.5 mg/L bleomycin). Single cell gel electrophoresis was adopted to investigate genotoxicity of the alloy samples in different groups, and 60 cells from each group were analysed. Tail moment and tail DNA percentage were used as reliable indicators to show DNA damage in lymphocytes induced by every testing sample. Student-Newman-Keuls (SNK) test was used to compare results from 4 groups.</p><p><b>RESULTS</b>There were no significant differences in tail moment and tail DNA percentage between magnesium alloy group [(0.52 +/- 0.12), (6.82 +/- 1.81)%] and magnesium alloy coated with beta-TCP group [(0.51 +/- 0.12), (6.89 +/- 1.93)%, P > 0.05]. Tail moment and tail DNA percentage in negative group were (0.47 +/- 0.14) and (6.29 +/- 1.64)%, and tail moment and tail DNA percentage in positive group were (5.17 +/- 1.23) and (22.09 +/- 4.51)%.</p><p><b>CONCLUSIONS</b>No significant increase was found in DNA damage in lymphocytes induced by magnesium alloy coated with beta-TCP.</p>