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Objective:To evaluate the role of Dorea in glucose intolerance of people with obesity. Methods:This study recruited 113 young individuals with obesity and varying degree of glucose tolerance [body mass index(BMI)≥30 kg/m 2] and 105 controls, comparing the metabolic phenotypes and Dorea abundance. Correlation analysis and ROC analysis were performed to assess the association between Dorea and clinical parameters and its predictive role in predicting glucose intolerance. Results:(1) Metabolic parameters were higher in obesity group than the control group. There was no difference in body weight, BMI and WHR among subgroups classified by glucose tolerance in people with obesity. (2) The abundance of Dorea, Dorea formicigenerans were higher in obese individuals, however showing a downward trend in accordance with glucose intolerance. The abundance was inversely associated with OGTT-2 h plasma glucose and HbA 1C, while positively associated with HOMA-β. Logistic regression demonstrated that Dorea formicigenerans was an independent protective factor after adjusting confounders such as age and gender in the prevention of glucose intolerance. (3) ROC analysis exhibited that the AUC values of Dorea formicigenerans was 0.73 in the total population. Conclusion:Dorea and Dorea formicigenerans exert protective effect on glucose metabolism in obese subjects. The abundance of Dorea and Dorea formicigenerans can be used as predictors of glucose intolerance risk in obese subjects, which facilitate the early screening and monitoring.
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ObjectiveTo explore the effect of Chaishao Liujuntang on Hedgehog signaling pathway in rats with chronic atrophic gastritis （CAG） of liver depression and spleen deficiency. MethodWistar rats were randomized into normal group and modeling group. CAG with the liver depression and spleen deficiency syndrome was induced in rats in the modeling group with a compound method. After modeling， they were classified into the model group， vitacoenzyme group， Chaishao Liujuntang group， GDC-0449 （blocker） group， and Chaishao Liujuntang + GDC-0449 group. Normal group and model group were given （ig） normal saline. Vitacoenzyme and Chaishao Liujuntang group received （ig） corresponding drugs at 240 mg·kg-1·d-1 and 5.1 g·kg-1·d-1， respectively， and GDC-0449 group was treated （ip） with GDC-0449 at 50 mg·kg-1·d-1. For the Chaishao Liujuntang + GDC-0449 group， rats received GDC-0449 （ip） at 50 mg·kg-1·d-1 and Chaishao Liujuntang （ig） at 5.1 g·kg-1·d-1. The administration lasted 4 weeks. The pathological morphology of rat gastric mucosa was observed based on hematoxylin-eosin （HE） staining. mRNA and protein expression of sonic hedgehog （Shh）， 12th transmembrane receptor Patched1 （Ptch1）， and glioma-associated oncogene homolog 1 （Gli1） in gastric mucosa tissues was detected by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot. Content of serum interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） was determined by enzyme-linked immunosorbent assay （ELISA）. ResultCompared with normal group， the model group demonstrated decrease in gland cells， glandular atrophy， large lumen volume， plasma cell infiltration， intestinal metaplasia， decrease in the mRNA and protein expression of Shh， Ptch1， and Gli1 in gastric mucosa （P<0.01）， and rise of serum IL-1β and TNF-α content （P<0.01）. Compared with model group， vitacoenzyme group and Chaishao Liujuntang group showed ordered cells， alleviation of gland atrophy， and no obvious inflammatory infiltration， and GDC-0499 group and Chaishao Liujuntang + GDC-0449 showed no significant improvement. Significant rise in the mRNA and protein expression of Shh， Ptch1， and Gli1 in gastric mucosa tissues of vitacoenzyme group and Chaishao Liujuntang group （P<0.01）， no significant difference in serum IL-1β content and significant decrease in TNF-α content in vitacoenzyme group （P<0.01）， significant reduction in content of serum IL-1β and TNF-α in Chaishao Liujuntang group （P<0.05， P<0.01） were observed compared with those in the model group. The mRNA and protein expression of Shh， Ptch1， and Gli1 in gastric mucosa and the content of serum IL-1β and TNF-α were insignificantly different between the GDC-0449 group and Chaishao Liujuntang + GDC-0449 group. ConclusionChaishao Liujuntang can effectively improve the pathological state of gastric mucosa in CAG rats with liver depression and spleen deficiency， which may be related to the activation of Hedgehog signaling pathway and the decrease of IL-1β and TNF-α content.
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Obesity is a chronic noncommunicable disease with a high tendency to rebound. Although successful weight loss can be achieved with multiple means, weight regain is common. Various compensatory mechanisms underlie such phenomenon, including alterations in adipocytes, energy metabolism, gut hormones, central appetite modulation, and gut microbiome. These changes may interact with each other through gut-brain axis, and influence long-term weight maintenance. The present review focuses on potential mechanisms of weight regain to shed light on further research in this field.
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Colorectal cancer (CRC) is one of the most prevalent, most lethal cancers in the world. Increasing evidence suggests that the intestinal microbiota is closely related to the pathogenesis and prognosis of CRC. The normal microbiota plays an essential role in maintaining gut barrier function and the immune microenvironment. Recent studies have identified carcinogenic bacteria such as enterotoxigenic Bacteroides fragilis (ETBF) and Streptococcus gallolyticus (S. gallolyticus), as well as protective bacterial such as Akkermansia muciniphila (A. muciniphila), as potential targets of CRC treatment. Gut microbiota modulation aims to restore gut dysbiosis, regulate the intestinal immune system and prevent from pathogen invasion, all of which are beneficial for CRC prevention and prognosis. The utility of probiotics, prebiotics, postbiotics, fecal microbiota transplantation and dietary inventions to treat CRC makes them novel microbe-based management tools. In this review, we describe the mechanisms involved in bacteria-derived colorectal carcinogenesis and summarized novel bacteria-related therapies for CRC. In summary, we hope to facilitate clinical applications of intestinal bacteria for preventing and treating CRC.
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Humans , Colorectal Neoplasms/therapy , Dysbiosis , Fecal Microbiota Transplantation , Gastrointestinal Microbiome , Prebiotics , Tumor MicroenvironmentABSTRACT
Objective To establish a mathematical prediction model for chronic obstructive pulmonary disease (COPD) by applying an artificial neural network (ANN) and logistic regression analysis method. Methods A cross-sectional survey was conducted in 2015 to collect epidemiological data of COPD of 2 400 residents from Hubei Province. Subjects were randomized into training group and test group at a ratio of 7:3. The prediction models of COPD were established using ANN and logistic multiple regression. The predictive performance of the two models was compared. Results Information from a total of 1 569 subjects was valid and analyzed, including 1,099 cases in the training group and 470 cases in the test group. The area under curve (AUC) of ANN for training group and test group was 0.80 and 0.78, respectively. The AUC of logistic regression for training group and test group was 0.75 and 0.74, respectively. Conclusion It is feasible to apply ANN and logistic regression models to predict COPD, which can provide scientific evidence for COPD prevention and treatment.
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OBJECTIVE@#To evaluate the efficacy and safety of Yangyin Yiqi Huoxue Granule (, YYHG) in the treatment of ischemic stroke (IS) patients with qi-yin deficiency and blood stasis syndrome (QYDBSS), and to explore its effective dosage.@*METHODS@#The total of 288 patients were randomly assigned to the YYHG high-dose, YYHG low-dose, positive control (administered Xiaoshuantong Granule, XSTG, ), or placebo control (administered inert granule) groups (72 cases per group) by software-drived competitive block randomization. The trial was conducted for a 28-day period, with a 180-day follow-up period. The primary outcome was the comprehensive curative evaluation, and secondary outcomes were the National Institute of Health Stroke Scale (NIHSS) score, Barthel activities of daily living (ADL) index score, the quality of life index (QLI) score, and the Chinese medicine syndrome (CMS) score. All analyses were done on an intention-to-treat basis. The clinical safety was also assessed.@*RESULTS@#The total of 288 participants were recruited between June 1, 2008 and September 30, 2009, and 287 patients received intervention; the treatment groups were well balanced at baseline. The comprehensive cure rates of YYHG high-dose, low-dose, positive and placebo control groups were 63.38%, 31.94%, 36.11% and 6.14%, respectively; there was a statistical difference between the two groups (P<0.01), while the high-dose YYHG treatment group was significantly higher than the other 3 groups (P<0.01). The improvement of NIHSS, ADL, QLI and CMS scores of the YYHG high-dose and low-dose groups was significantly better than that of the positive control group and the placebo control group (P<0.05). In terms of improving the classification of the NIHSS scale and the assessment of the ADL scale, the YYHG high-dose group was significantly better than the other three groups (P<0.05), and the YYHG low-dose group was better than the placebo control group (P<0.01). At the same time, except for the QLI score, the high-dose group was better than the low-dose group (P<0.05). In terms of safety, adverse reactions after YYHG treatment were generally mild (3.78%), and no serious adverse reactions have been reported.@*CONCLUSION@#YYHG is safe and effective in the treatment of IS patients with QYDBSS.
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Humans , Activities of Daily Living , Brain Ischemia/drug therapy , Ischemic Stroke , Qi , Quality of Life , Stroke/drug therapy , Yin DeficiencyABSTRACT
OBJECTIVE@#To investigate the synergistic effect of Naoxintong Capsule (NXTC, ) and Guhong Injection (GHI, ) on cerebral ischemia-reperfusion (I/R) injury.@*METHODS@#Forty-eight Sprague-Dawley rats were divided into 6 groups: control group, oxygen and glucose deprivation (OGD) group, nimodipine group (9.375 mg/kg), NXTC group (0.5 g/kg), GHI group (5 mL/kg) and NXTC+GHI group (0.5 g/kg NXTC+5 mL/kg GHI), after the onset of reperfusion and once per day for the following 7 days. Blood was collected 1 h after final administration, and the sera were collected. Cultured primary rat brain microvascular endothelial cells (rBMECs) were subjected to OGD to establish a cell injury model. Untreated rBMECs were used as blank control. The cell counting kit-8 assay was used to assess cell viability using the sera. Malondialdehyde (MDA) and superoxide dismutase (SOD) levels were assessed using an enzyme-linked immunosorbent assay. Apoptosis was evaluated after Hoechst33342 staining using fluorescence microscopy and flow cytometry. JC-1 staining was performed to assess changes in mitochondrial membrane potential.@*RESULTS@#Statistical analysis indicated that more than 95% of the cells were rBMECs. Compared with the OGD group, the cellular morphology of the all drug delivery groups improved. In particular, the combined drug group had the most significant effect. Compared with the OGD group, all drug intervention groups induced a decrease in the apoptotic rate of rBMECs, increased the SOD levels, and decreased the MDA levels (all P<0.01). Compared with the mono-therapy groups, the NXTC+GHI group exhibited a significant improvement in the number of apoptotic rBMECs (P<0.01). All drug intervention groups showed different degrees of increase in membrane potential, and the NXTC+GHI group was higher than the NXTC or GHI group (P<0.01).@*CONCLUSION@#The combinationa application of NXTC and GHI on cerebral I/R injury clearly resulted in protective benefits.
Subject(s)
Animals , Rats , Apoptosis , Brain , Brain Ischemia/drug therapy , Drugs, Chinese Herbal , Endothelial Cells , Glutamine/analogs & derivatives , Plant Extracts , Rats, Sprague-Dawley , Reperfusion Injury/drug therapyABSTRACT
Background: Colorectal cancer (CRC) is one of the most common cancers in China and even in the world, and metastasis is the main cause of death. However, there is lack of sufficient molecular biomarkers for predicting effectively the occurrence of metastasis. Aims: To explore the expression of fibulin-2 (FBLN2) in CRC and the underlying mechanism of its effect on tumor invasion and metastasis. Methods: Bioinformatics data of PRJNA218851 data set from the SRA database were extracted to screen CRC metastasis-associated genes. Then these differentially expressed genes were applied for gene enrichment analysis to identify the most significant pathways. Data from TCGA and clinical CRC samples were used to analyze the expression of FBLN2 in CRC tissues and normal tissues, and the relationship between FBLN2 and clinicopathological features and prognosis of CRC patients. Expression of FBLN2 in normal colorectal mucosal cell line, CRC cell lines, and clinical CRC samples was detected by real-time PCR. After FBLN2 was knockdown or over expressed in CRC cells, CCK-8 assay, clone formation assay, Transwell cell invasion and migration assay, and wound healing assay were performed to observe the effect of FBLN2 on the proliferation, invasion and migration abilities of CRC cells. Gene set enrichment analysis was conducted to screen the potential downstream pathway of FBLN2, and then the pathway screened was verified. Results: The expression of FBLN2 was low in eight CRC cell lines and CRC tissues, yet the expression in metastatic CRC was significantly higher than that in non-metastatic ones. Compared with CRC patients with low FBLN2 expression, CRC patients with high FBLN2 expression were prone to have lymph node metastasis and distant metastasis, and with higher clinical stage and poorer prognosis. Knockdown of FBLN2 could decrease the invasion and migration abilities of CRC cells, but had no impact on cell proliferation. FBLN2 was positively correlated with CDH2, Snai1 and vimentin, indicating that the epithelial-mesenchymal transition (EMT) pathway might be the downstream pathway of FBLN2. Conclusions: FBLN2 is low expressed in CRC but the expression is increased in metastatic CRC. Therefore, it might be used as a molecular biomarker for screening early metastasis. FBLN2 might enhance CRC invasion and metastasis through activating EMT pathway and is associated with poor prognosis.
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Objective:To identify human infection with Brucella suis, analyze its biological and molecular characteristics, and to provide basis for prevention and control of brucellosis. Methods:Brucella suis strains were isolated from the body of the first case of human Brucella suis infection in Jiangsu Province. Serum agglutination test was used for serotyping. The specific gene bcsp-31 of Brucella was detected by PCR. AMOS-PCR was used to identify IS-711. The species and biotypes were identified by multiplex PCR. The wboA gene products were sequenced and phylogenetic tree was constructed. Multilocus sequence analysis (MLSA) was used for molecular typing, and cluster analysis was performed with reference strains. Results:The strain was confirmed to be Brucella suis biotype 3 by serum agglutination test and PCR. After sequencing the wboA gene, cluster analysis of the reference sequence showed that the wboA gene was closest to the biotype 3 strain Brucella suis str. 686 (CP007719). MLSA was typed into ST17(1-6-4-1-5-3-5-2-4). Conclusions:Brucella suis biotype 3 is reported in Jiangsu Province for the first time. The MLSA type is ST17. In the future, the prevention and control of human brucellosis should be carried out. We should actively cooperate with the animal husbandry and veterinary department to increase the quarantine, immunization and other control measures.
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Objective:To explore more clinical characteristics and outcomes of children with severe pneumonia induced by adenovirus type 7(Adv-7).Methods:Seventy children with severe pneumonia induced by Adv-7 admitted to the pediatric intensive care unit of Guangzhou Women and Children′s Medical Center from January 2016 to October 2019 were enrolled.The clinical features, treatments and outcomes of these children were recorded.Results:(1)There were 43 males(61.4%)and 27 females(38.6%). Thirty(42.9%)patients were 0-12 months old, 28(40.0%)patients were 13-36 months old, and 12(17.1%)patients were over 36 months old.(2)The average onset time of severe pneumonia induced by Adv-7 was(11.87±7.10)days before being admitted to PICU.The average sequential organ failure assessment score was 6.80±3.13.The average Murray lung injury score was 2.49±1.15.The average P/F value was(150.57±86.25)mmHg(1 mmHg=0.133 kPa). Sixty-four cases(91.4%)were involved in two or more area of lung on X-rays.All cases were diagnosed with sepsis.(3)Laboratory examination: white blood cell count was(7.6±5.5) ×10 9/L, platelet count was(238.8±164.2)×10 9/L, and C-reactive protein was(39.4±37.2)mg/L.(4)Treatments: intravenous gamma globulin was used in 65 cases(92.9%). Intravenous glucocorticoid was used in 45 cases(64.3%). Fiberoptic bronchoscopy was performed in 43 cases(61.4%). Blood purification treatment was performed in 21 cases(30%). Sixty-three patients(90.0%)were treated with non-invasive or invasive ventilator, high frequency ventilator-assisted ventilation was used in 20 cases(28.6%). Surfactant was used in six cases(8.6%). Extracorporeal membrane oxygenation was used in 19 cases(27.1%). (5)The average treatment time for ventilation was(13.10±11.58)days.The average time for temperature recover was(4.69±4.01)days in PICU.The average PICU stay time was(15.76±12.20)days.The average length of stay was(27.04±13.10)days.There were 16 patients died and the mortality was 22.9%. Conclusion:The children with severe pneumonia induced by Adv-7 were critical and had significant lung injuries.Suffering from active clinical treatment such as extracorporeal membrane oxygenation, some of these patients still had poor prognosis.
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OBJECTIVE: To develop an ultra-high performance liquid chromatography coupled with quadrupole tandem time-of-flight mass spectrometry method for simultaneous determination of nine trace D-amino acids in thymalfasin, combined with deuterated acid hydrolysis and precolumn-derivatization. METHODS: The sample was hydrolyzed by deuterated acid, followed by precolumn-derivatization with Nα-(2, 4-dinitro-5-fluorophenyl)-L-alaninamide (FDAA). The analysis was then performed on an ACCQ-TAGTM ULTRA C18 column (2.1 mm×100 mm, 1.7 μm), with mobile phase comprising water containing 0.1% formic acid-acetonitrile gradiently eluted at a flow rate of 0.3 mL•min-1. Nine D-amino acids in thymalfasin were correctly quantified using standard curves by Xevo G2-S Q-TOF coupled with electrospray ion source in positive ion mode. RESULTS: The standard curves of the nine D-amino acids derivatives had good linearity in the ranges of the tested concentrations (r>0.991 2). The limits of quantitation of all D-amino acids derivatives were as low as 0.05-0.30 pmol. The precision and recoveries met the requirements of Chinese Pharmacopoeia (2015). The contents of D-amino acids in the samples from five companies were determined to be 25.16-1 322.01 μg•g-1. Among them, D-glutamate, D-aspartate, D-lysine and D-serine had higher contents, which were 1 105.45-1 322.01, 614.15-740.50, 358.06-388.76 and 138.78-291.60 μg•g-1, respectively. CONCLUSION: The method is sensitive, efficient and reliable, working well for simultaneous determination of nine trace D-amino acids in thymalfasin, which provides a reference for the comprehensive control of racemic peptide impurities in this synthetic polypeptide drug.
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We utilized a multi-step derivatization gas chromatography-mass spectrometry method for the determination of common amino acid enantiomers, combined with deuterated hydrochloric acid hydrolysis, to identify nine trace D-amino acids in thymalfasin. We optimized the conditions for multi-step derivatization, the volume of reagent for redissolving samples, and the conditions for chromatography and mass spectrometry with isopropanol and trifluoroacetic anhydride as derivatization reagents, and validated the procedure, including sensitivity, linear range, precision, accuracy and recovery. Sixteen pairs of D/L-amino acids and glycine derivatives were separated within 29 min, with the limit of quantification as low as 0.09-2.79 μmol·L-1. Nine amino acid derivatives of thymalfasin showed a good linear relationship within the concentration range examined (r2>0.992 3). The precision results showed that RSD values were less than 10.90%. Accuracy test results of a reference substance ranged from 76.69% to 128.18%. Average recoveries of spiked samples ranged from 70.41% to 125.39%. For the nine D-amino acids assayed, D-Asp and D-Glu content in six batches of thymalfasin were highest, ranging 0.41%-0.49% and 0.25%-0.33%, respectively, with others less than 0.25%. The method is sensitive, efficient and reliable, available for seventeen common amino acids and their enantiomers, and works well with simultaneous determination of nine trace D-amino acids in thymalfasin, providing a reference for the comprehensive control of racemic peptide impurities in this synthetic polypeptide drug.
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The animal model of hyperlipidemia in rats was established to investigate the lipid-lowering effect and mechanism of Danhong Injection on hyperlipidemic rats. SD rats were selected as the research object. The rats in normal group were fed with basic diet, and the rats in other groups were fed with high-fat diet to establish hyperlipidemia model. The successfully modeled rats were randomly divided into model group, Danhong Injection low, medium, high dose(1.0, 2.0, 4.0 mL·kg~(-1)) groups, and simvastatin(2.0 mg·kg~(-1)) group. Danhong Injection groups received intraperitoneal administration, and simvastatin group received intragastrical administration, once a day for 4 weeks. At the first, second, third, and fourth weekends after administration, blood was collected from the orbital vein to detect the levels of total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-C), and high-density lipoprotein cholesterol(HDL-C), and then the atherosclerosis index(AI) was calculated. After 4 weeks of administration, the animals were sacrificed, and their heart, liver, spleen, lung, kidney and adipose tissue were extracted and weighed respectively to calculate the organ index of each group. The expressions of acyl-coaoxidase 1(Acox1), adenosine 5'-monophosphate(AMP)-activated protein kinase alpha(AMPK-α), bile salt export pump(BSEP), peroxisome proliferator-activated receptor gamma(PPAR-γ), catalase(CAT) and superoxide dismutase(SOD) mRNA in liver tissues were detected by fluorescence quantitative PCR; the content of cholesteryl ester transfer protein(CETP) and lecithin cholesterol acyltransferase(LCAT) in serum was detected by ELISA. The results showed that as compared with the normal group, the levels of serum TC, TG and LDL-C in the model group were significantly increased, and the level of HDL-C was significantly decreased, indicating that the hyperlipidemia rat model was successfully constructed. As compared with the model group, Danhong Injection could decrease the contents of TC, TG, LDL-C and increase the content of HDL-C in hyperlipidemia rats; reduce the body weight of hyperlipidemia rats, and reduce the liver weight, liver index, fat weight and fat index; it had no significant effect on the main organ indexes such as heart, spleen, lung and kidney; but it could increase the expressions of Acox1, AMPK-α, BSEP, PPAR-γ, CAT and SOD mRNA in liver tissues of rats; it could also reduce the level of CETP and increase the level of LCAT in serum; and the regulatory effect of Danhong Injection groups all showed a dose-dependent effect. It can be concluded that Danhong Injection can regulate the blood lipid contents, reduce the blood lipid levels and alleviate the accumulation of body fat in rats with hyperlipidemia. The mechanism may be related to inhibiting lipid metabolism disorder and oxidative stress induced by high-fat diet feeding, and improving the imbalance of lipid transport system.
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Animals , Rats , Diet, High-Fat , Drugs, Chinese Herbal , Hyperlipidemias , Lipid Metabolism , Lipids , Liver , Rats, Sprague-Dawley , TriglyceridesABSTRACT
Obesity has become a global epidemic and is accompanied by a tremendously rising prevalence of its associated comorbidities.Bariatric surgery is currently the most effective approach to treat obesity and metabolic disturbances compared to traditional interventions.The present review focuses on the potential mechanisms of gut microbiota mediating the improvement in body weight and metabolism after bariatric surgery,including the change of bile acids,short-chain fatty acids,amino acids,lipopolysaccharides,trimetlylamine oxide as well as neurotransmitters.
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Objective To analyze the molecular characteristics of Brucella strains isolated from Nanjing,understand strains genotying and clustering,and to provide a basis for prevention and treatment of brucellosis.Methods Multilocus sequence typing (MLST) and multiple locus variable-number tandem repeat analysis (MLVA) were used to analyze and characterize Brucella ovis strains isolated from 7 cases of sporadic cases in Nanjing Drum Tower Hospital,the Affiliated Hospital of Nanjing University Medical School,from 2011-2016,and cluster analysis was did with reference strain data from Jiangsu Province.Results The results showed that 7 strains were defined as sequence type (ST) 8 by MLST.They were typed into 7 subtypes and clustered in the "Middle Mediterranean Cluster" by MLVA.Strain NJ-2011-1 and two strains isolated from other cities in Jiangsu had the same MLVA genotype.Conclusions The results reveal ST8 is the predominant genotype in Nanjing.They have clustered in the "Middle Mediterranean Cluster" by MLVA.The 7 strains are sporadic.The transmission routes and risk factors are more complicated in the city.Various departments should strengthen the cooperation to control the source.
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Chiral amino acid analysis is a sensitive, efficient and economical method for controlling racemic peptide impurities, especially for synthetic polypeptide drugs with complex composition of amino acids. Unexpected amino acid enantiomers in racemic peptides can be measured by chiral amino acid analysis coupled with mass spectrometry. The position of amino acid isomerization in the peptide segment can be accurately mapped by mass spectrometry, which lays a solid foundation for screening of racemic peptide impurities and rapid identification or quantification of trace racemic peptide impurities. Combination of the two techniques is vital for quality control of the synthetic polypeptide drugs and for research of polypeptide drugs based on chemical synthesis. The strategies of peptide hydrolysis have been summarized in this review. The latest chiral amino acid analysis based on mass spectrometry is briefly reviewed. Based on our knowledge, we have pointed to the direction of research and control of racemic peptide impurities in synthetic polypeptide drugs.
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To investigate the pharmacokinetic characteristics of active constituents of Guhong injection in rats with cerebral ischemia reperfusion injury. The middle cerebral artery occlusion (MCAO) model was established in our studies, and then all the rats received iv administration of Guhong injection (2.1 mL·kg⁻¹). The blood concentrations of aceglutamide and hydroxysafflor yellow A (HSYA) were determined by high performance liquid chromatography (HPLC) method at different time points. The concentration-time curves were drawn and pharmacokinetic data were obtained by DAS 3.2.6 software. The results showed that aceglutamide and HSYA showed good linear relationship within the ranges of 1.5-500 mg·L⁻¹ (R²=0.997 5) and 0.33-40 mg·L⁻¹ (R²=0.998 9) respectively. This quantitative method showed a high recovery rate, good precision and stability. The main pharmacokinetics parameters of t1/2α, t1/2β, CL₁, CL₂, AUC0-t, AUC0-∞, Vd1, and Vd2 were (0.139±0.007) and (0.155±0.017) h, (0.803±0.046) and (2.233±0.410) h, (0.016±0) and (0.149±0.018) L·h⁻¹·kg⁻¹, (0.015±0.001) and (0.446±0.016) L·h⁻¹·kg⁻¹, (133.335±3.844) and (9.298±0.179) mg·h·L⁻¹, (143.851±3.595) and (14.464±1.451) mg·h·L⁻¹, (0.009±0.001) and (0.223±0.007) L·kg⁻¹, (0.006±0.001) and (0.212±0.032) L·kg⁻¹, respectively. The results showed that the established HPLC method was highly specific, and could be used for the simultaneous detection of aceglutamide and HSYA of Guhong injection in MCAO rats, which was conducive to pharmacokinetic studies. Pharmacokinetic data and parameters could provide reference for continuous administration and interval administration of the drug.
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Aim To discuss the effect of Danhong in-jection(DHI) on hyperlipidemia in rats and its possible mechanism. Methods The hyperlipidemia model of rats were induced by high fat diet. The protein expres-sion of adenosine 5'-monophosphate-activated protein kinase(AMPK), p-AMPK, cholesterol-binding ele-ment binding protein (SREBP-1), adenylate-activated protein kinase carboxylasecetyl-CoA(ACC) and p-ACC in liver were detected using Western blot. Results The protein expression levels of AMPK, SREBP-1 and ACC significantly decreased (P<0.05), but the pro-tein expression levels of p-ACC and p-AMPK signifi-cantly increased (P<0.05). Conclusions Danhong injection can reduce the activity of SREBP-1 and ACC by enhancing the activation of AMPK, and effectively reduce the blood lipid level of hyperlipidemic rats by promoting fatty acid oxidation and reducing lipid depo-sition.
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Objective To observe the effect of Kidney-nourishing, Blood-activating, Phlegm-resolving and Resuscitation-inducing Decoction(KBPRD)on the expression of N-methyl-D-aspartate(NMDA)receptor subtype 1,2A,2B(NR1,NR2A,NR2B)in the cochlear spiral ganglion neurons(SGN)of tinnitus rats and to explore its mechanism, thus to provide experimental evidence for the treatment of tinnitus with KBPRD. Methods Sixty rats were randomly divided into normal group,model group,western medicine group,and low-,middle-,and high-dose Chinese medicine groups, 10 rats in each group. Rats were given intraperitoneal injection of sodium salicylate combined with water deprivation to induce tinnitus model. After successful establishment of the model, the rats in low-,middle-,and high-dose Chinese medicine groups were given gastric administration of KBPRD in the dosage of 5.5, 11, 22 g·kg-1·d-1 respectively, the rats in western medicine group were given gastric administration of 5 mg·kg-1·d-1 of carbamazepine,and rats in the model group and normal group were given gastric administration of 2 mL of normal saline,once every day,treatment time covering 8 weeks. The expression levels of NR1,NR2A,and NR2B in the cochlear SGN was detected by immunoblotting and real-time quantitative reverse transcription-polymerase chain reaction(qRT-PCR)after 8 weeks of treatment. Results Compared with the normal group,the expression levels of NR1, NR2A and NR2B in the model group were increased, the difference being significant (P < 0.05). Compared with the model group,the expression of NR1,NR2A and NR2B in low-,middle-,and high-dose Chinese medicine groups were significantly decreased(P<0.05).Conclusion KBPRD is effective on relieving tinnitus of rats, and its mechanism is correlated with lowering the increased expression of NR1,NR2A and NR2B in SGN of tinnitus rats.
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This paper aimed to investigate the effect of Yinhua Pinggan granule and San-ao decoction on the immunologic mechanisms of influenza viral pneumonia mice , in order to study the activity of the combined administration of different formulas on influenza A/H1N1 virus. The model of pneumonia was established in mice through nasal dropping influenza virus, and then divided randomly into five groups: normal control group, influenza virus model group, oseltamivir control group, Yinhua Pinggan granule group, and San-ao decoction group. The animals were put to death at the 5th day after gavage administration with the corresponding drugs. The contents in mice serum of TNF-α, IL-6 and IFN-γ were respectively measured by ELISA. The mRNA expressions of TLR3/7, MyD88, JNK, p38MAPK and NF-κB p65 in lung tissues were respectively detected by RT-PCR. The protein expressions of JNK, p38MAPK and NF-κB p65 in lung tissues were determined by immunohistochemical analysis, respectively. According to the results, Yinhua Pinggan granule and San-ao decoction could significantly decrease the levels of TNF-α and IL-6, increase the level of IFN-γ in mice serum of lung tissues, significantly reduce the gene expressions of TLR3/7, MyD88, JNK, p38MAPK and NF-κB p65 in influenza virus-infected mice lung tissues, and significantly reduce the protein expressions of JNK, p38MAPK and NF-κB p65 in lung tissues. Furthermore, the regulatory effect of Yinhua Pinggan granule was superior to that of San-ao decoction. In conclusion, Yinhua Pingan granule and San-ao decoction have the therapeutic effect on pneumonia mice infected by H1N1 virus . The anti-influenza mechanisms of Yinhua Pinggan granule and San-ao decoction may be the results of interactions by regulating the immunologic function of influenza virus-infected mice and TLR3/7 signaling pathway with multiple links of the gene and protein expressions. Moreover, the combined administration of warm-natured and cold-natured Yinhua Pinggan granule with the effects of detoxification and exhalation has a better effect than the single administration of warm-natured San-ao decoction.