ABSTRACT
Objective: Fufang Biejia Ruangan Tablet (FBRT) is widely used for the treatment of liver fibrosis. However, Hominis Placenta (HP), as an important adjuvant of FBRT, has been restricted for medicinal using due to the limited availability, ethical controversy and safety issues. The present study aimed to investigate the therapeutic effects of novel FBRT (N-FBRT) with sheep placenta (SP) as substitute for HP on liver fibrosis and explore its possible mechanisms. Different dosages of SP in N-FBRT were also evaluated. Methods: Rats were subcutaneously injected with CCl
ABSTRACT
Psoraleae Fructus (PF) is a well-known traditional herbal medicine in China, and it is widely used for osteoporosis, vitiligo, and other diseases in clinical settings. However, liver injury caused by PF and its preparations has been frequently reported in recent years. Our previous studies have demonstrated that PF could cause idiosyncratic drug-induced liver injury (IDILI), but the mechanism underlying its hepatotoxicity remains unclear. This paper reports that bavachin isolated from PF enhances the specific stimuli-induced activation of the NLRP3 inflammasome and leads to hepatotoxicity. Bavachin boosts the secretion of IL-1β and caspase-1 caused by ATP or nigericin but not those induced by poly(I:C), monosodium urate crystal, or intracellular lipopolysaccharide. Bavachin does not affect AIM2 or NLRC4 inflammasome activation. Mechanistically, bavachin specifically increases the production of nigericin-induced mitochondrial reactive oxygen species among the most important upstream events in the activation of the NLRP3 inflammasome. Bavachin increases the levels of aspartate transaminase and alanine aminotransferase in serum and hepatocyte injury accompanied by the secretion of IL-1β via a mouse model of lipopolysaccharide-mediated susceptibility to IDILI. These results suggest that bavachin specifically enhances the ATP- or nigericin-induced activation of the NLRP3 inflammasome. Bavachin also potentially contributes to PF-induced idiosyncratic hepatotoxicity. Moreover, bavachin and PF should be evaded among patients with diseases linked to the ATP- or nigericin-mediated activation of the NLRP3 inflammasome, which may be a dangerous factor for liver injury.
Subject(s)
Animals , Humans , Mice , Adenosine Triphosphate , Chemical and Drug Induced Liver Injury/etiology , Flavonoids , Inflammasomes , NLR Family, Pyrin Domain-Containing 3 Protein , NigericinABSTRACT
Objective:To investigate the effects of cattle encephalon glycoside and ignotin(CEGI)on the expression of glial fibrillary acidic protein(GFAP)and neuronal nuclear antigen(NeuN)in the brain of APP/PS1 model mice of Alzheimer's disease.Methods:A total of 36 5-month-old APP/PS1 dual-transgenic model mice were randomly divided into 3 groups: the model group(normal saline 6.6 ml·kg -1·d -1), CEGI group(CEGI 6.6 ml·kg -1·d -1)and donepezil group(donepezil 2 mg·kg -1·d -1), with 12 in each group.Twelve C57BL/6J mice of the same age were used as the normal control group.All mice were given drugs for 6 weeks consecutively.Brain tissue was collected for immunohistochemical staining to detect the expression of amyloid β-protein(Aβ), GFAP and NeuN, which were then analyzed quantitatively. Results:The results of immunohistochemical staining indicated that levels of Aβ and GFAP were higher and levels of NeuN were lower in the model group than in the normal control group(0.147±0.068% vs.0%, 61.750±22.020 vs.26.000±4.598, 0.021±0.002 vs.0.032±0.003, P<0.05). Levels of Aβ and GFAP were lower and levels of NeuN were higher in the CEGI group and the donepezil group than in the model group(0.058±0.055 % vs.0.057±0.045 %, 38.250±5.418 vs.36.130±5.963, 0.029±0.004 vs.0.027±0.003, P<0.05). There was no significant difference in the expression of Aβ, GFAP and NeuN between the CEGI group and the donepezil group( P>0.05). Conclusions:CEGI has multi-target neuroprotective effects via down-regulating the expression of Aβ and GFAP and up-regulating the expression of NeuN.
ABSTRACT
[This corrects the article DOI: 10.1016/j.apsb.2019.02.003.].
ABSTRACT
Aberrant activation of NLRP3 inflammasome has been implicated in the pathogenesis of diverse inflammation-related diseases, and pharmacological molecules targeting NLRP3 inflammasome are of considerable value to identifying potential therapeutic interventions. Cardamonin (CDN), the major active ingredient of the traditional Chinese medicinal herb , has exerted an excellent anti-inflammatory activity, but the mechanism underlying this role is not fully understood. Here, we show that CDN blocks canonical and noncanonical NLRP3 inflammasome activation triggered by multiple stimuli. Moreover, the suppression of CDN on inflammasome activation is specific to NLRP3, not to NLRC4 or AIM2 inflammasome. Besides, the inhibitory effect is not dependent on the expression of NF-B-mediated inflammasome precursor proteins. We also demonstrate that CDN suppresses the NLRP3 inflammasome through blocking ASC oligomerization and speckle formation in a dose-dependent manner. Importantly, CDN improves the survival of mice suffering from lethal septic shock and attenuates IL-1 production induced by LPS , which is shown to be NLRP3 dependent. In conclusion, our results identify CDN as a broad-spectrum and specific inhibitor of NLRP3 inflammasome and a candidate therapeutic drug for treating NLRP3 inflammasome-driven diseases.
ABSTRACT
Objective BALB/c mutant curly mice and normal BALB/c mice were genetically detected by microsatellite DNA marker analysis to detect the differential microsatellite loci between BALB/c mutant curly mice and normal mice.Methods 38 microsatellite DNA loci were selected and their variation in the BALB/c mutant curly mice, BALB/c mutant hairless mice and normal BALB/c mice were detected by multiplex fluorescence PCR and STR scanning genotyping.Results There were 27 the same microsatellite loci between the 38 microsatellite loci in BALB/c mutant curly mice and normal mice,and there were 11 differential loci, with a mutation rate of 28.9%(11/38). There were 30 the same sites between BABL/c mutant hairless mice and normal mice,and there were 8 different loci,with a mutation rate of 21.1%(8/38). There were also 12 differential loci between BABL/c mutant curly mice and hairless mice. Conclusions BALB/c mutant curly mice have a higher mutation rate and are significantly higher than those of hairless mice,demonstrating that the mutations in curly mice and hairless mice are two completely different mutations. These results provide reliable theoretical data for the future study and development of BALB/c mutant curly mice.
ABSTRACT
Objective To study the effects of simple portal hypertension on the endotoxin levels in serum and intestinal mucosa of rats. Methods A total of 16 rats were divided into the blank control group (4 rats) and the model groups (3-day group, 7-day group and 10-day group, 4 rats in each group). The rat model of partial portal vein ligation was established in the model groups, and samples of blood and jejunum, ileum and colon of the rats were taken on the 3rd, 7th and 10th days, respectively. Changes in the serum endotoxin levels were detected by ELISA. Histopathological changes of the intestinal tissues were examined by HE staining. Results The rat model of partial portal vein ligation was successfully established in all the model groups. The serum levels of endotoxin on the 3rd, 7th and 10th days in the model groups were not significantly different from that in the normal control group. Damages of different intestinal segments were not serious on the 3rd day after modeling. However, on the 7th day after modeling, there were some sowllen and damaged intestinal villi in the intestinal mucosa of each intestinal segment, and the connection between the epithelial cells and the lamina propria was broken, compared with that at 3 days after modeling. In addition, there were obvious damages in the intestinal mucosa and lamina propria on the 10th day, compared with that at 3 d and 7 d after modeling. Conclusions In the case of normal liver function, portal hypertension can cause intestinal mucosal damages within a short period of time, but the amount of endotoxin produced by intestine does not exceed the processing capacity of the liver and thus does not cause an increase in the serum endotoxin level.
ABSTRACT
Although oxymatrine (OMT) has been shown to directly inhibit the replication of hepatitis B virus (HBV), limited research has been done with this drug. In the present study, the antiviral effect of OMT was investigated in an immunocompetent mouse model of chronic HBV infection. The infection was achieved by tail vein injection of a large volume of DNA solution. OMT (2.2, 6.7 and 20 mg/kg) was administered by daily intraperitoneal injection for 6 weeks. The efficacy of OMT was evaluated by the levels of HBV DNA, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg) and hepatitis B core antigen (HBcAg). The immunoregulatory activity of OMT was evaluated by serum ELISA and flow cytometry. Results shows that OMT at 20 mg/kg inhibited HBV replication, and it was more efficient than entecavir (ETV) in the elimination of serum HBsAg and intrahepatic HBcAg. In addition, OMT accelerated the production of interferon-(IFN-) in a dose-dependent manner in CD4T cells. Our findings demonstrate the beneficial effects of OMT on the enhancement of immunological function and in the control of HBV antigens. The findings suggest this drug to be a good antiviral therapeutic candidate for the treatment of HBV infection.
ABSTRACT
Objective To evaluate the feasibility and safety of transjugular liver biopsy( TJLB) by using the LABS 200 liver access and biopsy set ( Cook Inc, USA) .Methods Five minipigs were operated though TJLB puncture under the imaging guidance.The liver biopsies were analyzed by histological examination.Results Technical success of TJLB was achieved in all the 5 minipigs.No procedure-related complications occurred, and sufficient amount of specimen for histological examination was obtained in all cases.Conclusions Our preliminary results indicate that transjugular liver biopsy with the use of Cook LABS 200 liver access and biopsy set is clinically safe and feasible, and provide technical support for its clinical application.
ABSTRACT
Objective To analyze the preventive and therapeutic effects of a traditional Chinese medicine Taohe Chengqi decoction on a rat models of hepatic encephalopathy ( HE) induced by thioacetamide ( TAA) .Methods The rat model of HE was established by intraperitoneal injection of TAA,and the effects of Taohe Chengqi decoction were observed by neurobehavioral changes,neurological test,blood ammonia,serum biochemical indexes,and liver and brain pathological examination.Results The rat model of hepatic encephalopathy was successfully established.Low, medium and high dose Taohe Chengqi decoction markedly improved neuro-reflexes and liver and brain pathological damages, and significantly decreased the HE staging and serum biochemical indexes, and the results of high dose group was the best, similar to that of positive drug-treatment group.Conclusions Taohe Chengqi decoction exhibits promising preventive and therapeutic effects on the rat model of TAA-induced hepatic encephalopathy, and these results provide substantial experimetal evidence for its clinical application.
ABSTRACT
Objective To establish a method for isolation of cynomolgus monkey umbilical cord mesenchymal stem cells.Methods Fresh cynomolgus monkey umbilical cord was directly minced into pasty fine pieces, and the pieces were cultured in tissue flask with DMEM/F12 medium supplemented with 10% fetal bovine serum.The morphological characteristics of the resulting cells were examined, and their expression of mesenchymal cell surface markers were analyzed by flow cytometry.The multidifferentiation potential was examined in vitro, too.Results The fibroblast-like cells were successfully isolated from the fresh umbilical cord by an adherent culture procedure.These adherent cells expressed mesenchymal markers including CD29, CD44, and CD90, and also could be induced to differentiate into adipocytes, osteoblasts and chondrocytes.Conclusion Mesenchymal stem cells can be isolated from fresh cynomolgus monkey umbilical cord by using an adherent culture procedure.
ABSTRACT
Objective To select a best mouse strain for establishing an animal model of orthotopic transplanted liver cancer through comparison analysis.Methods C57,C3H and BALB/c mice( each 10) were selected as model groupⅠ,Ⅱ and Ⅲ.H22 cells were inoculated into the liver parenchyma of mice in model group along the ventral midline laparotomy.Fifteenth days after injection of laparotomy,the rate of tumor was observed,the volume of ascites and gross tumor volume were measured,and tumor pathology was analyzed.Results The survival rate of mice in three groups was 100%. After 15 days,ascites in three groups were produced,but with no significant difference among the three groups of the volume of ascites.Tumor transplantation rate in model groupⅠwas 100%,which was higher than 60%in model groupⅡand 30%in model group Ⅲ.Liver tumors in model group Ⅰ were all large compact grayish white lesions, and the average tumor volume was significantly greater than that of model group Ⅱ and Ⅲ( P <0.05 ) .Pathology results confirmed that white lesions in liver of three groups were hepatocelluar carcinoma in situ.Conclusion C57 is the better ideal experimental animal for establishing orthotopic liver caner model,and these results will provide a good experimental platform for research in pathogenesis of hepatocellular carcinoma.
ABSTRACT
Objective To observe the effects of resveratrol on blood pressure and cardiac function in the rats with vascular calcification induced by vitamin D3 plus nicotine.Methods 32 male SD rats were randomly divided into the following groups for treatment:Control (Con), calcified (Cal), Cal+Res low dose [L] and Cal+Res high dose [H] groups.Blood pressure, cardiac function, alkaline phosphatase ( ALP ) activity in serum or aorta were detected and HE staining was used for pathological examination at 6 weeks after treatment.Results Compared with the Con group, LVW/BW, heart rate, systolic aortic pressure, pulse pressure, mean blood pressure, left ventricular systolic pressure and ALP activity in serum or aorta of rats in the Cal group were increased by 27.3%, 8.8%, 22.8%, 47.5%, 13.6%, 19.0%, 280%and 265%( P<0.05 or P<0.01) , respectively.Compared with the Cal group, pulse pressure and ALP activity in serum or aorta of rats in the Cal+Res [L] group were decreased by 8.5%, 34.5%and 29.5%(P<0.05 or P<0.01), respectively, and LVW/BW, systolic aortic pressure, pulse pressure, mean blood pressure, left ventricular systolic pressure and ALP activity in serum or aorta of rats in the Cal +Res [ H] group were decreased by 14.2%, 13.6%, 23.7%,10.0%, 9.0%, 53.1%and 45.9%(P<0.05 or P<0.01), respectively.Compared with the Cal+Res [L] group, systolic aortic pressure, pulse pressure, left ventricular systolic pressure and ALP activity in serum or aorta of rats in the Cal+Res [H] group were decreased by 8.3%, 16.7%, 5.8%, 28.4% and 23.2% (P<0.05 or P<0.01), respectively.Compared with the aorta in the Con group, pathological examination revealed thickened vessel walls and disordered elastic fibers in the calcified aortas.However, the thickness of aortic wall in the Cal+Res [ L] and Cal+Res [ H] groups was reduced and elastic fibers were regularly arranged.Conclusion Resveratrol can effectively reduce the blood pressure and improve the cardiac function in rats with vascular calcification.
ABSTRACT
Objective To compare the rat and mice intestine slides quality fixed with three different fixatives and embeded by paraffin.Methods Three kinds of conventional fixatives were selected for the test, they are 10% neutral buffered formalin,Bouin’s solution and modified Davidson’ s solution.SD rat’ s and KM mice’ s intestinal tissues were fixed with the three different fixatives, then embeded, sliced and stained with HE as routine rut.To observe the slides quality under microscope.Results Sheding and necrosis of intestine villus epithelia were observed in slides made from formalin fixed intestines, which is speculated due to the fixations.The phenomenon was not observed in Bouin's solution and modified Davidson’ s solution fixed tissues.And the tissue structure were more fine and clear in them.Conclusions The rat and mice intestine slides made from tissues fixed by Bouin's solution and modified Davidson's solution are better than from the 10%neutral buffered formalin fixed ones.
ABSTRACT
Objective To investigate if there are differences in hematological indexes between BALB/c mutant curly mice and normal BALB/c mice.Methods 6 week old BALB/c mutant curly and normal BALB/c mice of each 20 ( male and female) were selected, and 8 blood routine indexes and 15 serum electrolytes and biochemical indexes were detected using automatic blood cell analyzer and automatic biochemical detection, and the results of two groups were compared.Results The sex and group results of WBC,MCV,PLT and MCHC between BALB/c mutant curly mice and normal mice have significant differences ( P <0.05, P<0.01 );the sex and group results of Na+、K+and Cl-between BALB/c mutant curly mice and normal mice have significant differences( P<0.05,P<0.01);the sex and group results of ALT、GLU and TG between BALB/c mutant curly mice and normal mice have significant differences(P<0.05,P<0.01). Conclusion Some hematological indexes between BALB/c mutant curly and normal BALB/c mice are different clearly, and these results will provide the theoretical references for researching and using mutant curly mice model.
ABSTRACT
Objective To explore the humoral and cellular immune responses of a vaccine of S fragments from a new type reovirus R4 strain in mice.Methods Four recombinant plasmids were constructed by respectively cloning S 1, S2, S3,S4 genes into pcDNA3.1+, and mice were intramuscularly immunized with the recombinant plasmids in a dose of 100 μg/mouse.Control vector pcDNA3.1 +and phosphate buffered saline (PBS) were used as negative controls.The spe-cific antibody level and IgG subclass (IgG1, IgG2a, and IgG2b) were detected by ELISA, and cellular immune responses to R4 were assessed using an interferon ( IFN)-γELISpot assay .Results All recombinant plasmids induced significantly higher levels of anti-R4 IgG compared with that of the controls (pcDNA3.1 +and PBS), and the titers were highest in the mice immunized with S1 and S3.On the other hand, S1 gene induced highest IgG2a antibody and the cellular immune re-sponse was best .Conclusions After the mice immunized with S 1 gene recombinant plasmid , this plasmid can initiate both cellular and humoral immune responses in mice .S1 gene recombinant plasmid is a promising vaccine candidate .
ABSTRACT
Objective Previous studies showed that hypoxia preconditioning could protect cardiac function against subsequent myo-cardial infarction injury. However, the effect of hypoxia on left ventricular after myocardial infarction is still unclear. This study therefore aims to investigate the effects of hypoxia training on left ventricular remodeling in rabbits post myocardial infarction. Methods Adult male rabbits were randomly divided into three groups: group SO (sham operated), group MI (myocardial infarc-tion only) and group MI-HT (myocardial infarction plus hypoxia training). Myocardial infarction was induced by left ventricular branch ligation. Hypoxia training was performed in a hypobaric chamber (having equivalent condition at an altitude of 4000 m, FiO214.9%) for 1 h/day, 5 days/week for four weeks. At the endpoints, vascular endothelial growth factor (VEGF) in the plasma was measured. Infarct size and capillary density were detected by histology. Left ventricular remodeling and function were as-sessed by echocardiography.Results After the 4-week experiment, compared with the group SO, plasma VEGF levels in groups MI (130.27 ± 18.58 pg/mL,P< 0.01) and MI-HT (181.93 ± 20.29 pg/mL,P< 0.01) were significantly increased. Infarct size in Group MI-HT (29.67% ± 7.73%) was deceased remarkably, while its capillary density (816.0 ± 122.2/mm2) was significantly increased. For both groups MI and MI-HT, left ventricular end-diastolic and end-systolic dimensions were increased whereas left ventricular ejection fraction was decreased. However, compared with group MI, group MI-HT diminished left ventricular end-diastolic (15.86 ± 1.09 mm,P< 0.05) and end-systolic dimensions (12.10 ± 1.20 mm,P< 0.01) significantly and im-proved left ventricular ejection fraction (54.39 ± 12.74 mm,P< 0.05).ConclusionHypoxia training may improve left ven-tricular function and reduce remodeling via angiogenesis in rabbits with MI.
ABSTRACT
The study is aimed to investigate the effect of lamivudine on growth and metabolism of three intestinal characteristic bacteria (namely, Bifidobacterium adolescentis, Escherichia coli and Shigella dysenteriae). The growth condition of the three bacteria was quantitatively evaluated by microcalorimetry with four characteristic parameters of the thermal power-time curves, including the growth rate constant (k), thermal power (p), time to peak (t) and calorific value (Q). The results showed that the IC50 value of lamivudine on B. adolescentis was 200 microg x mL(-1), and the IC50 values of lamivudine on S. dysenteriae and E. coli were higher than 3 000 microg x mL(-1) and 6 000 microg x mL(1), respectively. Therefore, lamivudine made different inhibitory effects on the three bacteria, in which the B. adolescentis was most susceptible to lamivudine. This work showed that taking lamivudine chronically is likely to affect the balance of good flora in the intestinal tract, and might increase endotoxin release, leading to inflammation and disease progression in hepatopathy.
ABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of curcumin on the expression of synapse-related proteins PSD-95 and Shank1 in APP/PS1 double transgenic mice.</p><p><b>METHOD</b>Three-month-old APP/PS1 dtg mice were randomly divided into the model group, the positive Rosiglitazone control group and curcumin high (400 mg x kg(-1) x d(-1)), medium (200 mg x kg(-1) x d(-1)) and low (100 mg x kg(-1) x d(-1)) dose groups, with non-genetically modified mice with the same background as the normal group. After the oral administration for three months, immunohistochemistry and Western blot were adopted for detection.</p><p><b>RESULT</b>According to the behavioral detection, the treatment group and the model group showed differences in the place navigation test and the spatial probe test to varying degrees (P < 0.01 or P < 0.05). The expression of PSD-95 and Shank1-positive cells of hippocampus CA1 region significantly decreased in model mice compared with normal control group (P < 0.01); while the curcumin intervention group showed recovery to some extend. Western blot results showed that the strap of PSD-95 protein expression became significantly thinner and lighter in the model group compared with the normal control group (P < 0.01); while the curcumin intervention group showed notably thicker and darker straps of PSD-95 protein expression (P < 0.05).</p><p><b>CONCLUSION</b>Curcumin can increase the expression of synapse-related proteins PSD95 and Shank1 in APP/PS1 double transgenic mice, improve structure and plasticity of synapse in APP/PS1 double transgenic mice and enhance their learning and memory abilities.</p>
Subject(s)
Animals , Mice , Amyloid beta-Protein Precursor , Genetics , CA1 Region, Hippocampal , Metabolism , Curcumin , Pharmacology , Disks Large Homolog 4 Protein , Gene Expression Regulation , Guanylate Kinases , Metabolism , Membrane Proteins , Metabolism , Mice, Transgenic , Nerve Tissue Proteins , Metabolism , Presenilin-1 , Genetics , Synapses , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To observe the effect of curcumin on the expression of Abeta42 and its degrading enzyme NEP in APP/PS1 double transgenic mice.</p><p><b>METHOD</b>3-month old APP/PS1 dtg mice were randomly divided into model group, positive control group and curcumin large, medium and small dose group. After 3 months, Morris water maze, immunohistochemistry, Western blot were applied to detect learning and memory ability of animal.</p><p><b>RESULT</b>Behavior detection, compared with the model group, treatment group showed varying degrees of difference in place navigation test and space exploration experiments (P < 0.01 or P < 0.05). The expression of Abeta42 and its degrading enzyme NEP, Abeta42-positive cells of hippocampus CA1 region significantly increased in model mice as compared with normal control group (P < 0.01).</p><p><b>CONCLUSION</b>Curcumin can improve learning and memory ability of APP/PS1 double transgenic mice through increasing the expression of Abeta-degrading enzyme NEP and decreasing the expression of Abeta42.</p>