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@#Objective To develop a kinetic chromogenic quantitative method for the determination of endotoxin content in intermediate of pertussis antigen,and to verify the method so as to better control the quality of diphtheria,tetanus,and pertussis vaccine(DTP vaccine).Methods A kinetic chromogenic assay[Limulus Amebocyte Lysate(LAL)]was developed to detect the endotoxin content in the intermediate products of pertussis antigens after detoxification,and verified for the linearity,specificity,accuracy,reproducibility and intermediate precision. The quantitative detection results of kinetic chromogenic assay were compared with those of gel method.Results The absolute value of the linear correlation coefficient（|r|）of the kinetic chromogenic assay was more than 0. 99;under the maximum effective multiple dilution,the interference test recovery of the intermediate was within 50% — 200%,and pertussis toxin(PT)diluted to 10,100 and 1 000 times,filamentous hemagglutinin(FHA)diluted to 3 000,5 000 and 10 000 times,and pertussis adhesin(PRN)diluted to 50,75 and 100 times had no interference effect on the experiment after detoxification;the accuracy verification recovery rates of PT,FHA and PRN were 125%,110% and 99% respectively;and the CVs of reproducibility verification were 7. 21%,8. 31% and 5. 84%,and the CVs of intermediate precision verification were 6. 04%,16. 29% and 12. 23%,respectively.The bacterial endotoxin content of the three batches of pertussis antigen intermediates detected by kinetic chromogenic assay was consistent with that verified by gel method,both of which were less than the limit of bacterial endotoxin in the intermediates of pertussis antigen after detoxification.Conclusion The developed kinetic chromogenic assay has good linearity,specificity,accuracy and precision with accurate detection results,which can be used to detect the endotoxin content in intermediate products of component pertussis antigen after detoxification.
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Bacillus thuringiensis is a worldwide known bacterium for its capacity to control insect pests thanks to the action of its parasporal crystal. The objective of this paper deals with the history, in some cases unknown, of the study of Bacillus thuringiensis that led it to be a crucial biological alternative in controlling pest insects. How the mode of action for killing insects was understood, as well as the field tests that were carried out to evaluate its effectiveness and to develop the first commercial products, are reflected in this review that presents and discusses the scientific successes and failures that marked the course of B. thuringiensis.
Bacillus thuringiensis es una bacteria conocida mundialmente por su capacidad para controlar insectos plaga, gracias a la acción de su cristal parasporal. El objetivo de esta revisión trata de la historia, en algunos casos desconocida, del estudio de Bacillus thuringiensis que la llevó a ser una importante alternativa biológica en el control de insectos plaga. Cómo se llegó a comprender el modo de acción para matar insectos, así como las pruebas de campo que se realizaron para evaluar su efectividad y lograr desarrollar los primeros productos comerciales están plasmados en esta revisión que presenta y discute los aciertos y desaciertos científicos que marcaron el rumbo de B. thuringiensis.
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@#Clostridiodes difficile(C.difficile)is the most common causative agent of antibiotic-associated diarrhea(ADD)in the world. In recent years,with the emergence of highly resistant and virulent strains,the outbreaks of C.difficile infection have occurred around the world. The incidence,recurrence and mortality of C.difficile infection are on the rise worldwide,and bring great challenges to clinical treatment. Pathogenic strains mainly produce two homologous glycosylation toxins A and B,which can cause symptoms ranging from diarrhea to highly lethal toxic megacolon. In view of the malignant consequences caused by C.difficile infection,disease prevention is still an important way worth exploring. Until now there is no approved vaccine against C.difficile. Therefore,this review assessed the status and challenge of clinical trials of vaccine research for C.difficile.
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Objective:To analyze the value of serum related cytokines in predicting intestinal mucosal injury in patients with severe acute pancreatitis (SAP) and its correlation with intestinal mucosal injury.Methods:A total of 92 patients with SAP admitted to the First Hospital of Qinhuangdao from January 2020 to December 2021 were included in the study. According to the presence or absence of intestinal mucosal barrier dysfunction, the patients were divided into intestinal mucosal barrier dysfunction group (33 cases) and non-intestinal mucosal barrier dysfunction group (59 cases). Another 100 healthy subjects were selected as the control group. Clinical data of the subjects were collected. Serum levels of procalcitonin (PCT), D-lactic acid (D-L), endotoxin, diamine oxidase (DAO), citrulline and intestinal fatty acid binding protein (I-FABP) of the three groups were compared, and the correlation between the above indexes was analyzed by Pearson correlation analysis. Receiver operating characteristic (ROC) curve was used to analyze the value of each indicator in predicting intestinal mucosal barrier dysfunction in SAP patients.Results:The levels of serum PCT, D-L, endotoxin, DAO and I-FABP in intestinal mucosal barrier dysfunction group, non-intestinal mucosal barrier dysfunction group and control group showed a downward trend, while the level of serum citrulline showed an upward trend, with statistically significant difference (all P<0.05). Pearson correlation analysis showed that serum citrulline was negatively correlated with serum PCT, D-L, and endotoxin levels ( r=-0.740, -0.629, -0.310, all P<0.05); There was a positive correlation between serum DAO and serum PCT, D-L and endotoxin levels ( r=0.482, 0.779, 0.338, all P<0.05); There was a positive correlation between serum I-FABP and serum PCT, D-L and endotoxin levels ( r=0.613, 0.421, 0.341, all P<0.05). The ROC curve results showed that the area under the curve (AUC) of serum PCT, D-L, endotoxin, DAO, citrulline, and I-FABP predicting intestinal mucosal injury in SAP patients were 0.816, 0.789, 0.732, 0.801, 0.812, and 0.857, respectively. The AUC of the combination of the above indicators predicting intestinal mucosal barrier dysfunction in SAP patients was 0.909, significantly higher than that predicted by each index alone (all P<0.05). Conclusions:The occurrence of intestinal mucosal barrier dysfunction in SAP patients may be related to the increase of serum PCT, D-L, endotoxin, DAO, I-FABP levels and the decrease of citrulline levels. It may be considered to predict the risk of intestinal mucosal injury by detecting the levels of various indicators in patients′ serum.
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Objective:To evaluate the clinical efficacy of continuous renal replacement therapy (CRRT) with adsorptive filter oXiris in the treatment of severe acute pancreatitis (SAP).Methods:The clinical data of 5 SAP patients who received the treatment of absorptive filter oXiris in Department of Critical Care Medicine of Shanghai General Hospital from February 2021 to February 2022 were collected. The changes of inflammatory indicators, hemodynamics, acid-base balance indicators and organ function indicators were compared before and 24 h after treatment.Results:Before the treatment of oXiris, 3 patients had pancreatic necrotic infection, and all the five patients had systemic inflammatory response syndrome(SIRS), acute respiratory and circulatory failure and acute renal injury. At 24 h after the treatment with oXiris, the levels of inflammatory indicators such as white blood cell count [(13.4±5.0)×10 9/L vs (25.8±10.0)×10 9/L), CRP [(149.6±68.3)mg/L] vs (289.0±129.4)mg/L] and procalcitonin [3.7(1.4, 17.7)ng/ml vs 12.2(3.2, 62.9)ng/ml] in the blood samples from the patients were greatly decreased. Hemodynamics were obviously improved; heart rate [(107.4±9.5)bpm/min vs (143.4±9.7)bpm/min] was decreased, and the mean artery pressure [(87±5)mmHg vs (73±13)mmHg], 1 mmHg=0.133 kPa] tended to be stabilized. Metabolic acidosis was significantly improved; pH value (7.4±0.0 vs 7.2±0.1) and base excess (-2.1±2.5 vs -14.5±6.1) were increased, while lactic acid [(2.6±1.2)mmol/L vs (10.62±6.55)mmol/L] was decreased. Organ dysfunctions were improved; PaO 2/FiO 2 value (241.7±58.5 vs 115.9±53.6) was increased, while serum creatinine [(148.0±42.5)μmol/L vs (232.8±77.4)μmol/L], intra-abdominal pressure [(18.6±4.5)mmHg vs (24.2±4.0)]mmHg, modified Marshall score [3(3.0, 4.0) vs 6(5.5, 9.0)] and APACHEⅡ score (17.6±2.9 vs 26.0±5.2) were decreased. All the differences above were statistically significant (all P value <0.05). Conclusions:It is safe and feasible to treat SAP patients with CRRT by using oXiris in clinical practice, which may have the functions of clearing inflammatory mediators, stabilizing hemodynamics and acid-base balance and improving organ function.
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@#As a powerful pyrogen substance,bacterial endotoxin in small amounts can cause many serious effects on human health and would cause fever,microcirculation disorders,endotoxemia,endotoxin shock,diffuse intravascular coagulation and even death.Therefore,it is very important to detect endotoxin in pharmaceutical products.In recent years,due to overfishing of horseshoe crab and environmental deterioration,the number of horseshoe crab in China is decreasing rapidly.It has been listed as the second-class protected animal in China,and the traditional endotoxin detection methods of limulus amoebocyte lysate will be replaced gradually.With the deepening of research,a series of rapid,sensitive and accurate methods for endotoxin detection have been developed.This paper reviews various endotoxin detection methods,focusing on their innovations such as recombinant factor C method and biosensor method,and elaborates their advantages,disadvantages and development trends with the hope that new detection technologies will be more widely developed and applied.
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The new type coronavirus disease 2019 (COVID-19) is a contagious disease of severe lung inflammation induced by 2019 novel coronavirus (2019-nCoV). The World Health Organization (WHO) nomenclature of the newly discovered coronavirus was 2019-nCoV and the disease caused by 2019-nCoV was named COVID-19 on January 12, 2020. After 2019-nCoV invasion into a human body, it can stimulate the human immune system and engender a large number of cytokines, triggering a cytokine storm, resulting in severe infection, acute lung injury, multiple organ dysfunction, etc. Therefore, theoretically, the removal of over-production of cytokines can avoid the occurrence of cytokine storm and reduce the incidence of severe critical COVID-19 and serious poor prognosis. In this review, the authors systematically reviewed the past published reports related to the occurrence of cytokine storm in sepsis resulting in deterioration of disease situation, and recently they analyzed the therapeutic effects of patients with severe critical COVID-19 using endotoxin adsorption membrane for treatment in the disease course, further providing the effective clinical evidence of applying endotoxin adsorption membrane for treatment of COVID-19.
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ObjectiveTo evaluate the curative effect of Jiedu Huayu granules （JDHY） in the treatment of chronic liver failure （CLF） with the syndrome of toxic heat and stasis and investigate the influence on the inflammatory state. MethodA total of 136 patients were randomly divided into a control group and an observation group with 68 cases in each group. In addition to the comprehensive western medicine treatment， patients in the control group received Yinchen Haotang granules orally at 1 dose/day and those in the observation group received JDHY at 10 g/time，3 times/day. The treatment lasted for eight weeks. The endotoxin （ET），diamine oxidase （DAO），aromatic amino acids （AAA），branched chain amino acids （BCAA），blood ammonia，calcitonin （PCT），tumor necrosis factor-α （TNF-α），interleukin （IL）-1，IL-6，IL-17，regulatory T cells （Treg cells），helper T cells 17 （Th17），Th17/Treg ratio，total bilirubin （TBil），albumin （Alb），alanine aminotransferase （ALT），aspartate aminotransferase （AST），prothrombin activity （PTA）， and D-dimer （D-D） levels before and after treatment were detected. The Child-Pugh grading scores of liver function， toxic heat and stasis syndrome scores， and the model scores of end-stage liver disease（MELD） before and after treatment were recorded. The fatality rate and survival were recorded at the follow-up for 48 weeks. ResultCompared with the control group after treatment， the observation group showed decreased ET，DAO， and blood ammonia， increased BCAA/AAA ratio （P<0.01）， reduced PCT，TNF-α，IL-1，IL-6， and IL-17 （P<0.01）， elevated Treg cells， dwindled Th17 and Th17/Treg ratio （P<0.01）， diminished TBil，ALT，AST， and D-D levels， and up-regulated Alb and PTA（P<0.01）. The Child-Pugh grading score，MELD score， and toxic-heat and stasis syndrome score of the observation group were lower than those of the control group （P<0.01）. The total response rate in the observation group was 93.65% （59/63），which was higher than 79.03% （49/62） in the control group （χ2=5.683，P<0.05）. The fatality rate of the observation group eight weeks after treatment was 6.35% （4/63），which was lower than 19.35% （12/62） of the control group （χ2=4.757，P<0.05）. There was no significant difference in mortality between the two groups 16，24， and 48 weeks after treatment. As revealed by the Log-rank test，the difference in survival curves between the two groups was not statistically significant. ConclusionJDHY can remove toxins from the body，regulate immune function，relieve inflammation，improve liver function， and reduce the severity of the disease in CLF patients with the syndrome of toxic heat and stasis. It is significant in clinical efficacy and worthy of clinical application.
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Objective:To explore the relationship between intestinal flora disorder and intestinal barrier dysfunction in patients with sepsis.Methods:A prospective observational study was conducted to include 10 patients with sepsis (sepsis group) admitted to the ICU of General Hospital of Ningxia Medical University from February 2017 to June 2017, 10 normal postoperative patients (non-sepsis group) admitted to the ICU of General Hospital of Ningxia Medical University in the same period, and 10 healthy persons (control group) were served as controls. General information was recorded. Fecal samples of the three groups of experimental subjects were detected and analyzed by using 16S rRNA gene sequencing technology. The venous blood of the sepsis and non-sepsis groups were collected and the levels of D-lactic acid and bacterial endotoxin in were measured by enzymatic method at the corresponding time points. The correlation between the levels of D-lactic acid and bacterial endotoxin and intestinal flora of patients with sepsis was analyzed.Results:The change consistency of pathogenic bacteria between clinical infection and intestinal pathogenic bacteria in patients with sepsis was observed and analyzed. Sputum culture of patients with sepsis was Acinetobacter baumannii (corresponding patient number: S5, S6, S8), Stenotrophomonas maltophilia (corresponding patient number: S6, S7), and Enterococcus (corresponding patient number: S7). In the intestinal flora of corresponding patients, the OUT abundance were increased. Patients with sepsis (corresponding patient number S7) showed E. coli in blood culture, and in his intestinal flora the OUT abundance was increased. Correlation analysis showed that the serum D-lactic acid level was negatively correlated with the proportion of Firmicutes in intestinal flora in the non-sepsis and sepsis groups, while was positively correlated with the proportion of Firmicutes (r value: -0.532, 0.468, respectively, P<0.05). Conclusions:The gut microbiota dysbiosis is correlated with intestinal barrier function in sepsis patients with sepsis. The spread of pathogenic bacteria between clinical infection and intestinal bacteria in sepsis patients has potential consistency.
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Bacterial endotoxin is considered as one of the critical risk factors in medical devices, especially implanted devices that directly or indirectly contact with blood circulating system. In that case, endotoxin limits for implanted medical devices is important in determine the safety of medical devices. According to GB/T 14233.2-2005, the requirements of endotoxin index for intrathoracic medical devices is 2.15 EU per device. However, the definition of "intrathoracic medical devices" is vague. Specifically, "for cardiovascular system application" instead of "intrathoracic application" is more reasonable. With the deeper understanding of the risk of endotoxin in medical devices and considering the internationally accepted standards, the limits of endotoxin in medical devices for cardiovascular system application is acceptable at 20 EU per device.
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EndotoxinsABSTRACT
Aim To establish a batch of endotoxin standard for baeterial endotoxin detection of insoluble samples.Methods Candidate A and candidate B were prepared by freeze -drying bacterial endotoxin without excipient.The two batches of candidates were calibrated by three methods, including 13 laboratories for gel method, 9 laboratories for kinetic-turbidimetric assay and 5 laboratories for kinetic chromogenic assay.Results After statistical analysis, the geometric mean values of gel method, kinetic-turbidimetric assay and kinetic chromogenic assay calibration of candidate A were 680.1 EU, 827.0 EU and 800.8 EU, with RSD of 22.4%, 16.2% and 16.7%, respectively.The P value of variance analysis of calibration results of the three methods was 0.067, showing no significant difference.The weighted mean of potency was 774.0 EU (95% confidence interval 721.0 - 831.0, FL% 7.10).The geometric mean values of the calibration of candidate B by gel method, kinetic-turbidimetric assay and kinetic chromogenic assay method were 1 640.6 EU, 1 828.6 EU and 3 224.8 EU, with RSD of 33.9% , 47.0% and 54.4% , respectively.The P val¬ue of variance analysis of the calibration results of the three methods was 0.030, showing significant differ¬ence.Chi-square test was used to correct the weight of each method , and weighted average of the results of the three methods was used to obtain a corrected weighted average efficiency value of 1 822.7 EU (95% confi¬dence interval 1 548.7 -2 145.2, FL% 16.4).Can¬didate B was eliminated based on the results.Conclu¬sion Candidate A has become the first batch of na¬tional standard bacterial endotoxin (for insoluble sam¬ples only) approved by National Standard Substance Committee of China, and the potency is 700 EU.
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Aim To explore the feasibility of the micro- dynamic chromogenic method for quantitative detection of bacterial endotoxin in recombinant novel coronavirus vaccine ( CHO cell).Methods The micro-dynamic color method of Limulus reagent was used to establish a bacterial endotoxin standard curve.The dilution factor was determined through interference pre -experiment, the recoverv rate of the endotoxin added to the test so- J lution was determined, and the interference test to complete the quantitative detection test of the bacterial endotoxin content in the test product was performed, and the results were compared with those of the gel-clot method.Results Hie linear range of the concentration of the standard curve was 0.02 to 2.0 EU • mL 1 , and the regression equation of the standard curve was lgT =-0.302 7 lgC +2.858 7( r = 0.998 9).When recombinant novel coronavirus vaccine ( CHO cell) was cliluted 40 times or below, the micro -dynamic chromogenic reagent did not interfere with the bacterial endotoxin agglutination reaction, and the recovery rate was 50% to 200%.The test results were consistent with the gel- clot method.Conclusions The micro-dynamic chromogenic method can be used for the quantitative detection of bacterial endotoxins in recombinant novel coronavirus vaccine ( CHO cell) with accurate results, high sensitivity, and process monitoring.
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Aim To evaluate the equivalence between micro kinetic chromogenic assay anrl kinetic chromogenic assay in order to provide data support for the use of alternative methods.Methods Detection conditions; micro kinetic chromogenic assay and kinetic chromogenic assay limulus reagent were used, sample amount of each well and limulus reagent was 25 jxL ( kinetic chromogenic assay was 100 jxL) , detection wavelength was 405 nm, ONSET OD value was 0.03, and half- well elisa plate was used for detection ( kinetic chromogenic assay was ordinary ELISA plate).The equivalence of the two methods was evaluated by various statistical methods, such as equivalence test, in collaboration with four laboratories in China.Results The results of one-way an OVA, paired T test and equivalence test were consistent, indicating that there were some differences between the existing kinetic chromogenic assay of different manufacturers, while there was no significant difference between the trace or conventional amount of reagent used by each manufacturer.Conclusions Micro kinetic chromogenic assay is e- quivalent to existing reagents in terms of accuracy and recoverv.J.
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Abstract; Aim To solve the problems in the appliea- tion of egg yolk leeithin endotoxin test method, and and to establish the baeterial endotoxin examination method for egg yolk lecithin (for injeetion). Methods The ethanol solution of Tween 80 ( the volume ratio of tween 80 to anhydrous ethanol was 2. 5 • 2. 7, mixed for 4 min) was used to prepare lecithin solution of egg yolk at 0. 1 kg • L 1 , and 10 test water was added to 1 mL lecithin solution of egg yolk (500 EU • mL 1 standard solution of endotoxin IOjxL was added for pos¬itive control). After diluted 20 times with endotoxin test water, the standard curve range was 10 ~0. 01 EU • mL 1 by kinetic-turbidimetrie assay. Methodology of endotoxin test was studied using limulus lysate from two manufacturers and eight hatches of samples. Results The recoveries of eight hatches of samples all met the requirement of interference test between 50% and 200% stipulated in the pharmacopoeia, which solved the problems of the current endotoxin test method in practical application. Conclusions The bacterial en¬dotoxin test method of egg yolk lecithin with good dura-bility is established to provide the basis for the revision of pharmacopoeia.
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Aim To design and implement the bacteri¬al endotoxin test proficiency testing plan to evaluate the laboratory's ability and level to determine bacterial en¬dotoxin. Methods According to the Chinese Pharma-copoeia (2015 edition, Vol IV) -1143 Bacterial Endo¬toxin Test-Photometric Method ( Method 2 ) , each la¬boratory used any of these methods to determine the endotoxin content of the sample to be tested. The stati- stical software JMP13 was used for statistical analysis of the feedback results of the participating laboratories. The consensus value of the participants, namely the ro¬bust average value of the effective test results of all the participating laboratories, was used as the assigned value X of the endotoxin content of the samples to be tested in the proficiency testing of the round. The re¬sults of participating laboratories were evaluated ac¬cording to the following criteria: (1) the laboratory test results were within 50% to 200% of the assigned value of the sample, which was evaluated satisfactory; ( 2 ) the laboratory test results were not within the 50 -200% range of the assigned value of the sample, which was evaluated dissatisfactory. Results A total of laboratories participated in this capacity verification plan, with 45 in the laboratory with satisfactory re¬sults, with a satisfaction of 91. 8% ; There were 4 la¬boratories that received "dissatisfaction" results, all of which were not within the range of 50% -200% of the assigned value of samples, and the dissatisfaction of 8. 2% . Conclusions Most of the participating labora¬tories can accurately detect the bacterial endotoxin con¬tent in the sample to be tested, indicating that the level of bacterial endotoxin detection in our country is gener¬ally good at present.
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Objective:By establishing the rats model of sepsis induced by endotoxin, exploring the effects of agmatine on the apoptosis of splenocyte and dendritic cells in the septic rats.Methods:SD rats ( healthy and clean, male, 90) were randomly(random number) divided into control groups, endotoxin groups and agmatine groups, 30 rats per group. The control groups were injected with normal saline via femoral vein (10 mL/kg), endotoxin groups were injected with lipopolysaccharide via femoral vein (10 mg/kg), agmatine groups were injected with lipopolysaccharide via femoral vein (10 mL/kg) and intraperitoneal injected of agmatine (200 mg/kg).The three groups were randomly selected 10 rats separately at 0 h, 12 h, 24 h (marked as 0 h, 12 h, 24 h subgroups, n=10) , anesthetized to death. Weigh the spleen; HE staining was used to observe the pathological changes of the spleen; The cell apoptosis of splenocyte and dendritic cells were detected by flow cytometry. The results were statistically analyzed using SPSS 17.0 software, analyzed by independent sample t test, P<0.05 was considered statistically significant. Results:The weights (g) of spleen in 12 h (1.2633±0.0652) , 24 h (1.5576±0.0711) subgroups of the endotoxin groups were increased significantly than the corresponding subgroups[(0.8876±0.0361),(0.9079±0.0425)]of the control groups ( P<0.05) , the 12 h (1.1052±0.0585) , 24 h (1.3262±0.0682) subgroups of the agmatine groups were decreased significantly than the corresponding subgroups of the endotoxin groups ( P<0.05) . HE staining showed that the spleen tissue inflammatory reaction in the endotoxin groups were worse than the control group ( P<0.05) , the agmatine groups were better than the endotoxin group ( P<0.05) . The apoptosis rates of the splenocyte[(13.31±1.26)、(19.53±1.68)]and dendritic cells[(19.5±1.52)、(16.09±1.15)]in the spleen from 12 h, 24 h subgroups of the endotoxin groups were significantly higher than the corresponding subgroups[(6.27±0.71),(6.01±0.67) and (4.99±0.51)、(5.30±0.66)]of the control groups ( P<0.05) , the 12 h[(9.19±0.95),(12.19±1.25)], 24 h [(12.71±1.19),(10.76±1.09)subgroups of the agmatine groups were significantly lower than the corresponding subgroups of the endotoxin groups ( P<0.05) ; The apoptosis rates of the splenocyte in the 24 h subgroups of the endotoxin groups and the agmatine groups were significantly higher than the 12 h subgroups of the same group ( P<0.05) , but the apoptosis rates of the dendritic cells were significantly lower than the 12h subgroups of the same group ( P<0.05) . Conclusion:The apoptosis of splenocyte and dendritic cells were closely related to the occurrence and development of sepsis, Agmatine could inhibit the apoptosis of splenocyte and dendritic cells the rats with sepsis.
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Dendrobii officinalis, with a definite effect of nourishing Yin and clearing heat, has been a folk habit for drinking after being mixed with water. Because its superfine powder has the advantages of high dissolution and convenient drinking, we observed the effect of D. officinalis superfine powder on metabolic hypertension model rats and its possible mechanism in this experiment, which can be used as a reference for its clinical application for hypertension. The overeating greasy-induced metabolic hypertension model was established with high-fat, high-sugar and high-purine diet. These rats were orally administered with 400 mg·kg~(-1) and 200 mg·kg~(-1) of D. officinalis superfine powder for 20 consecutive weeks. During this period, blood pressure, blood lipid, blood glucose, insulin and other related indexes of glucose and lipid metabolism were monitored; the levels of lipopolysaccharide(LPS), C-reactive protein(CRP), interleukin 6(IL-6) and other inflammatory mediators were measured; the levels of nitric oxide(NO) and endothelin-1(ET-1) were detected, and the histomorphological and ultrastructural changes of aorta were observed. In addition, the expression of LPS/TLR4 pathway-related molecules in aorta was determined. The results showed that long-term administration of D. officinalis superfine powder significantly reduced the levels of systolic blood pressure(SBP), diastolic blood pressure(DBP) and mean arterial pressure(MBP) in metabolic hypertension model rats, decreased the levels of total cholesterol(TC), triglyceride(TG), low density lipoprotein cholesterol(LDL-c), glucose(Glu), and insulin(INS) levels in blood, increased the contents of high density lipoprotein cholesterol(HDL-c),decreased the LPS, CRP, IL-6 and ET-1 levels in blood and increased NO content. Furthermore, it improved the abnormality of aortic histomorphology and endothelial ultrastructure, and inhibited the protein expression of TLR4, myeloid differentiation factor(MyD88), IL-6, interleukin-1 β(IL-1β), and tumor necrosis factor-α(TNF-α) as well as mRNA expression of TNF-α and IL-1β in aorta. In conclusion, D. officinalis superfine powder may improve the abnormal function and structure of blood vessels by inhibiting the activation of LPS/TLR4 pathway, thus playing a role against metabolic hypertension.
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Animals , Rats , Dendrobium/chemistry , Drugs, Chinese Herbal/pharmacology , Hyperphagia , Hypertension/drug therapy , Interleukin-6 , Powders , Tumor Necrosis Factor-alphaABSTRACT
Although microRNA-155 (miR-155) is considered a pro-inflammatory mediator, cumulative evidence indicates that it also has anti-inflammatory effects in macrophages and dendritic cells. In this study, we identified the dramatic expression changes of more than half of potential miR-155-targeted genes upon lipopolysaccharide (LPS) stimulation; 223 genes were down-regulated and 85 genes were up-regulated, including suppressor of cytokine signaling 1 (
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@#Periodontitis is an infectious disease caused by a variety of microorganisms. Fusobacterium nucleatum is closely related to periodontitis with a high detection rate. Fusobacterium nucleatum is able to coaggregate with other microorganisms and attach and invade epithelial cells with the help of adhesins. It can also promote the occurrence and development of periodontal diseases and even systemic diseases by destroying periodontal tissues with virulence factors and metabolites and inducing a host immune response. However, at present, drugs assisting periodontal nonsurgical treatment clinically cannot target specific periodontal pathogens, such as Fusobacterium nucleatum, which may lead to problems such as dysbacteriosis or drug resistance. Therefore, studies on the pathogenic mechanism of Fusobacterium nucleatum provide new ideas for the prevention and treatment of periodontitis. The idea is to develop materials, drugs, or probiotics that target adhesins, virulence factors, and metabolites or cut off each pathogenic pathway of Fusobacterium nucleatum to inhibit its proliferation and inflammatory responses in deep periodontal pockets and achieve a balance with other oral microorganisms, and the host is beneficial for the control of periodontitis.
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The aim of this paper was to explore the effect and mechanism of Jiawei Baitouweng Decoction(JWBTW) against ulcerative colitis(UC) from the perspective of intestinal mucosal tight junction proteins. From 60 SPF-grade male SD rats, 10 were randomly selected as the blank control, and the remaining 50 were treated with 3% dextran sodium sulfate(DSS) solution to induce UC and then randomized into the model group, mesalazine group, and low-, medium-, and high-dose JWBTW( L-JWBTW, M-JWBTW and H-JWBTW) groups, with 10 rats in each group. After successive medication for 14 days, the rat general conditions like body weight and stool were observed and the disease activity index(DAI) was calculated. The pathological changes in colon tissue was observed under a microscope for injury severity scoring and histopathological scoring. The serum endotoxin content was determined by limulus assay, followed by the measurement of protein expression levels of ZO-1, occludin, claudin-1, p38 MAPK, MLCK, MLC2 and p-MLC in colon tissue by Western blot. The results showed that compared with the blank group, the model group exhibited significantly reduced body weight, elevated DAI, injury severity and histopathological scores and serum endotoxin content, up-regulated protein expression levels of p38 MAPK, MLCK, MLC2 and p-MLC, and down-regulated ZO-1, occludin and claudin-1. Compared with the model group,mesalazine and JWBTW at each dose obviously increased the body weight, lowered the DAI, injury severity and histopathological scores and serum endotoxin content, down-regulated the protein expression levels of p38 MAPK, MLCK, MLC2 and p-MLC, and up-regulated the ZO-1, occludin and claudin-1, with the most obvious changes noticed in the H-JWBTW group. All these have indicated that JWBTW exerts the therapeutic effect against UC by inhibiting the activation of p38 MAPK/MLCK pathway, reversing the protein expression levels of occludin, claudin-1 and ZO-1, decreasing the serum endotoxin content, promoting the repair of intestinal mucosal mechanical barrier, maintaining the integrity of tight junctions, and reducing the permeability of intestinal mucosa.