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Objective@#The effect of total flavonoids of litchi (TFL) on nuclear translocation of nuclear factor-kappa B (NF- kappa B) in rat hepatic stellate cell line (HSC-T6) induced by transforming growth factor - beta 1 (TGF- beta 1) in vitro was studied to explore the mechanism of action of anti-hepatic fibrosis drugs.@*Methods@#HSC-T6 was cultured in vitro, induced by TGFβ1 for 24 h, and then treated with TFL at 125, 250 and 500 μg/ml for 48 h. The effect of TFL on NF-κB nuclear translocation in HSC-T6 was observed by confocal laser microscopy. The effects of TFL on the expression of TLR4, p-IκB ɑ, p-NF-κB p65, NF-κB and Collagen I protein were detected by western blot. The expressions of TLR4 and p-NF-κB p65 were detected by immunofluorescence. Data were presented as mean±SEM. Homogeneity test of variance was performed and then followed by one-way analysis of variance (ANOVA). The multiple comparisons between groups were performed by LSD test. P < 0.05 was considered statistically significant.@*Results@#Confocal laser scanning microscopy showed TFL inhibited the nuclear translocation of NF-κB in activated HSC-T6 in a concentration-dependent manner and TFL down regulated the protein expression levels of TLR4, p-IκB ɑ, p-NF-κB p65, NF-κB and collagen I protein in HSC-T6 in a concentration-dependent manner.@*Conclusion@#The mechanism of TFL against hepatic fibrosis may be related to the inhibition of nuclear translocation of NF-κb in the activated HSC-T6 and the expression of TLR4, P-iκbɑ, P-nf-κb p65, NF-κb and collagen I protein in HSC-T6.
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Trillions of microbes inhabit the human gut, not only providing nutrients and energy to the host from the ingested food, but also producing metabolic bioactive signaling molecules to maintain health and elicit disease, such as cardiovascular disease (CVD). CVD is the leading cause of mortality worldwide. In this review, we presented gut microbiota derived metabolites involved in cardiovascular health and disease, including trimethylamine-N-oxide (TMAO), uremic toxins, short chain fatty acids (SCFAs), phytoestrogens, anthocyanins, bile acids and lipopolysaccharide. These gut microbiota derived metabolites play critical roles in maintaining a healthy cardiovascular function, and if dysregulated, potentially causally linked to CVD. A better understanding of the function and dynamics of gut microbiota derived metabolites holds great promise toward mechanistic predicative CVD biomarker discoveries and precise interventions.
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Humans , Cardiovascular Diseases , Metabolism , Microbiology , Pathology , Gastrointestinal Microbiome , MetabolomeABSTRACT
Objective To evaluate the effect of polydatin on neuropathic pain in rats.Methods Forty male Sprague-Dawley rats,aged 6-8 weeks,weighing 200-230 g,were randomly divided into 5 groups (n =8 each) using a random number table:sham operation group (group S),neuropathic pain group (group NP),polydatin 5 mg/kg group (group P1),polydatin 10 mg/kg group (group P2),and polydatin 20 mg/kg group (group P3).Neuropathic pain was induced by chronic constriction injury in NP and P1-3 groups.In group S,the sciatic nerve was only exposed but not ligated.In S and NP groups,normal saline 0.1 ml was injected intraperitoneally immediately after operation and at 1,3,5 and 7 days after operation (T1-4).In P1-3 groups,polydatin 5,10 and 20 mg/kg (in normal saline 0.1 ml) were injected intraperitoneally immediately after operation and at T1-4.At 1 day before operation (T0) and T1-4,the mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured.After measurement of pain threshold at T4,the rats were sacrificed,and L4-6 segments of the spinal cords were removed for determination of the expression of high-mobility group box 1 (HMGB1),Toll-like receptor 4 (TLR4),interleukin-1beta (IL-1β),tumor necrosis factor-alpha (TNF-α) and monocyte chemotactic protein-1 (MCP-1) by Western blot.Results Compared with group S,the MWT was significantly decreased,and the TWL was significantly shortened at T1-4 in group NP,the MWT was significantly decreased at T1-4,and the TWL was significantly shortened at T2-4 in group P1,the MWT was significantly decreased at T1-4,and the TWL was significantly shortened at T3.4 in group P2,the MWT was significantly decreased at T1-4 in group P3,and the expression of HMGB1,TLR4,IL-1β,TNF-α and MCP-1 was significantly up-regulated in NP,P1 and P2 groups (P＜0.05).Compared with group NP,the MWT was significantly increased at Tt-4,and the TWL was significantly prolonged at T1,2 in group P2,the MWT was significantly increased,and the TWL was significantly prolonged at T1-4 in group P3,the expression of HMGB1,TLR4,IL-1β,TNF-α and MCP-1 was significantly down-regulated in P2 and P3 groups (P＜0.05),and no significant change was found in the parameters mentioned above in group P1 (P＞0.05).Compared with group P1,the MWT was significantly increased at T4 in group P2,and the MWT was significantly increased at T14,the TWL was significantly prolonged at T3,4,and the expression of HMGB1,TLR4,IL-1β,TNF-α and MCP-1 was significantly down-regulated in group P3 (P＜0.05).Compared with group P2,the MWT was significantly increased at T3,4,and the expression of TLR4,IL-1β,TNF-α and MCP-1 was significantly down-regulated in group P3 (P＜0.05).Conclusion Polydatin can alleviate neuropathic pain through inhibiting inflammatory responses in the spinal cord of rats.
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Objective To investigate the effects of total flavonoids of litchi chinensis sonn (TFL) on cell proliferation and the molecular mechanism in rat hepatic stellate cells (HSC-T6) activated by growth factor-β1 (TGF-β1). Methods HSC-T6 cells were treated by 0.25%Trypsin-EDTA and then were digested into single cell suspension by DMEM (10%FBS included), which were mixed with TGF-β1 (5μg/L). (1) MTT method was used to detect the proliferation of HSC-T6 cells. Cells were cultured in 96-well plate and were treated by different concentrations of TFL including TGF-β1 group, the control group (5‰DMSO included), and different concentrations of TFL groups (80, 160, 320, 640 and 800 mg/L TFL). Each group has three wells. The absorbance (A) value was measured by enzyme standard meter at the 490 nm wavelength after 24 h, 48 h and 72 h treatment. The cell inhibitory rate was calculated. The subsequent experimental drug concentration and drug treatment time were determined according to half inhibitory concentration (IC50). (2) The expression levels of NF-κB andα-SMA mRNA were detected by PCR (for mRNA) and Western blot assay (for protein). Cells were cultured in the 10 cm culture dish and were divided into different TGF-β1 groups, including TGF-β1 group, the control group (5‰DMSO included), and different concentrations of TFL groups (125, 250 and 500 mg/L TFL). After 48 h, related indicators were measured. Results At the same treatment time point, with the increased concentrations of TFL, A values were gradually decreased, and the cell inhibitory rates were gradually increased. There were no significant differences in the expressions of NF-κB andα-SMA mRNA between TGF-β1 group and control group. And there were no significant differences in the expressions of NF-κB andα-SMA mRNA between TFL125 group, TGF-β1 group and control group. There was a gradually decrease in the expressions of NF-κB andα-SMA mRNA and protein with the increased concentrations of TFL. Conclusion TFL can inhibit TGF-β1-induced HSC-T6 cell proliferation, which is involved in the inhibited expressions of NF-κB andα-SMA to anti-fibrotic effects in liver fibrosis.
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Objective To observe the effects of total flavone from litchi chinensis sonn (TFL) on the liver function in-cluding p16 protein, pro collagen type 3 (PC3) and pro collagen typeⅠ(PCⅠ) in model rats with liver fibrosis induced by bile duct ligation. Methods Forty rats were randomly divided into four groups:sham operation (SO) group, bile duct liga-tion (BDL) group, TFL group and silibinin (SIL) group. Rats were gavaged with saline (5 mL·kg-1·d-1) in SO and BDL group, rats were gavaged with TFL (200 mL·kg-1·d-1) in TFL group and rats were gavaged with SIL (5 mL·kg-1·d-1) in SIL group for four weeks. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin direct (BILD) and bilirubin total (BILT) were detected in four groups. The liver tissues were stained by HE and Masson methods. The ex-pression levels of p16, PC3 and PCⅠin liver tissues were determined by Western blot assay. Results The serum levels of ALT (44.6 IU/L±8.0 IU/L), AST (103.8 IU/L±18.1 IU/L), BILD (0.76 μmol/L±0.28μmol/L) and BILT (1.48μmol/L±0.35μmol/L) were lower in SO group. There was a higher level of ALT in BDL group (147.4 IU/L±86.3 IU/L) than that of TFL group (92.9 IU/L±47.3 IU/L). The serum level of ALT was higher in AST group (362.7 IU/L±106.6 IU/L) than that of TFL group (290.1 IU/L ± 171.7 IU/L) and SIL group (250.2 IU/L ± 54.9 IU/L). The serum level of BILD was lower in BDL group (99.71μmol/L±40.87μmol/L) than that of SIL group (137.01μmol/L±38.86μmol/L). The serum levels of BILD and BILT were significantly lower in TFL group (81.48μmol/L±47.50μmol/L, 106.64μmol/L±61.04μmol/L) than those of SIL group (P<0.05). There were small amount of new bile duct and no obvious cells degeneration, small amount of infiltration of in-flammatory cells and collagen deposition in TFL group. The liver fibrosis improved significantly in TFL group than that of BDL group. There were more new bile duct in hepatic portal area in SIL group than those of TFL group. The expression levels of p16, PC3 and PCⅠwere significantly higher in BDL group than those of TFL group. The expression level of PC3 was significantly lower in BDL group than that of SIL group. The expression level of PCⅠwas significantly higher in BDL group than that of SIL group (P<0.05). There was no significant difference in the expression level of p16 between BDL group and SIL group. The expression levels of PC16 and PC3 were significantly lower in TFL group than those of SIL group (P<0.05). There was no significant difference in the ex-pression level of PCⅠbetween TFL group and SIL group. Conclusion TFL can improve the liver function in model rats with choles-tatic liver fibrosis and reduce liver fibrosis, which may be related with inhibitory effects on the expressions of p 16, PC3 and PCⅠ.
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Objective To evaluate the effectiveness of web-based mental health services.Methods Web-based mental health services were established in our hospital to offer continuing medical education on mental health and psychological assessments.The access of clinicians to psychiatric knowledge and consultation from psychiatry department was evaluated.Results A total of 803 medical staff took the continuing medical education,and 643 passed the examination.Five hundred and twenty-eight online psychological assessments were completed.The qualification rate of psychiatric examination was 83.3％ vs.31.7％ in educated and non-educated clinicians (x2=32.77,P＜0.01).The common consultation from psychiatry department of the educated group involved anxiety,depression/mania and delirium,of which anxiety and medically unexplained symptoms were comparatively higher while delirium was lower than the non-educated group (x2 values were 4.80,4.59 and 5.16,respectively; all P＜0.05).More use of online psychological assessments was found in the educated group (33.8％ vs.7.6％) before asking for a consultation from psychiatry department (x2=30.04,P＜0.01).Conclusions Online mental health continuing education and psychological assessment could improve psychiatric knowledge and recognition of anxiety and depression in clinicians.
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ObjectiveTo monitor the early blood lactic acid concentration of patients with severe trauma who have been experienced routine surgery or damage control surgery,and explore the influence of surgical methods for the early lactate clearance rate.MethodsSelected 40 patients with severe trauma,they were divided into two groups with 20 cases each in accordance with the adopted operation mode,reference group by damage control surgery,and control group by routine surgery.Recorded acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ ) in patients after admission,blood lactic acid concentration at 6 h after admission and admission,calculated the early lactate clearance rate.ResultsIn reference group,blood lactic acid concentration at 6 h after admission was significantly lower than that in control group[ (3.5 ± 1.1 )mmol/L vs.(4.2 ± 1.4) mmol/L,P＜ 0.05 ],early lactate clearance rate was higher than that in control group [ (24.6 ± 6.3 )％ vs.( 11.4 ± 5.3 )％,P＜ 0.05 ].Conclusions Damage control surgery in patients with severe trauma in favour of the early removal of lactic acid,maintaining the homeostasis of the organism,is the key to improve the achievement ratio of treatment with severe trauma.
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Objective:To explore the interns' degree of lost basic science and the influence on studying clinical knowledge.Method:Medical students attending the third(n=100) and the fifth(n=100) of medical studies selected randomly from the Guilin Medical School were given the same test composed of 20 pairs of questions and each pair contains one basic and one clinical question which were correlative.The scores of the two groups were compared.Result:Third year students scored significantly higher in basic than clinical questions(P0.05).Conclusion:There is a positive relationship between mastery of basic knowledge and the ability of dealing with clinical problems.Quite a few basic knowledge of medical students is lost when they begin clinical practice.
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The therapeutic potential of soluble TRAIL (sTRAIL) in hepatocellular carcinoma(HCC) was studied. The expression of TRAIL receptors was detected in 60 HCC tissues, 20 normal liver samples and 2 HCC cell lines (HepG2 and SMMC-7721) by in situ hybridization. Before and after HepG2 and SMMC-7721 were treated with sTRAIL protein with various concentrations,the apoptosis rate was observed by using flow cytometry and in situ terminal deoxynucleotidyl tranferase (TdT) labeling. The results showed death receptor 4 (DR4) and DR5 were expressed in 60 HCC tissues and 20 normal liver samples, while the expression intensity of DR in HCC tissues was stronger than in normal liver samples. DcR1and DcR2 were not detectable in 54 (90 %) and 25 (41.7 %)HCC tissues, while in 20 normalliver samples, DcR was detectable. The high expressionof DR and low expression of DcR in HCC tissues were significantly differed from the low expression and high expression in normal liver samples. The expression of DR5, DR4 and DcR2 in both HCC cell lines was detectable, but the expression of DcR1 was not detectable. The expression of DR in HCC tissues was related to the differentiation and grades of HCC. In the poor differentiated HCC, the expression of DR was decreased (P＜0.01). The expression of DR in Ⅲ/Ⅳ grades was significantly lower than that in Ⅰ / Ⅱ grades (P＜0.05). The expression of DR was not related to gender, age, HBsAg, AFP, tumor sizeand metastasis. The expression of DR in the HCC drugresistant lines was decreased. After treatment with TRAIL (100 ng/ml) for 24 h, the apoptosis rate of HCC cells, Jurkat cells and human cholangiocarcinoma cell line QBC939 was 10 %, 70 %,50 % respectively. It was suggested that the TRAILR expression is prevalent in HCC with different expression patterns of different receptor types. HCC is resistant to TRAIL-mediated apoptosis.The treatment of TRAIL alone has a limited effect on inducing apoptosis of HepG2 and SMMC-7721.