Vitaminas B1, B6, B12 y neuropatías periféricas: Consenso de expertos / Vitamins B1, B6, and B12 and peripheral neuropathies: International expert consensus

RESUMEN A partir de una revisión bibliográfica de la literatura se ha planeado y desarrollado un consenso de expertos internacionales sobre la utilización de las vitaminas B1, B6, B12 en sus déficits y en la neuropatía periférica que puede estar asociada a la misma, como tema que precia de esa aproximación aclaratoria para optimizar su manejo. Se plantearon varias cuestiones de discusión que se consideraron importantes y dignas de ser abordadas y aclaradas, conservando nueve de ellas para su discusión ulterior buscando el consenso en tres rondas consecutivas. Se han propuesto 41 recomendaciones sobre el manejo de estas condiciones, con unanimidad por parte de los participantes en el consenso. Con ellas se ha intentado aclarar puntos oscuros o controvertidos, facilitando la actitud del clínico ante ellos en la práctica médica actual.

ABSTRACT Based on a bibliographic review of the literature, a consensus of international experts has been carried out on the use of vitamins B1, B6, B12, in their deficiencies, and in the peripheral neuropathy that may be associated with them, to optimize the management of these conditions. Several questions considered important and worthy of being addressed and clarified were raised, retaining nine of them for further discussion to achieve consensus. Forty one recommendations on the management of these conditions have been proposed, with unanimity of the participants in the consensus. This has been an attempt to clarify controversial points, assisting the clinician's attitude in current medical practice.

HMGB1 gene knockout alleviates acute lung injury of sepsis mice via inhibiting TLR4/NF-κB pathway / 安徽医科大学学报

Objective To study the effect of high mobility group box B1(HMGB1)gene knockout on alleviating a-cute lung injury and inhibiting toll-like receptor 4(TLR4)/nuclear factor-KB(NF-κB)pathway of sepsis mice.Methods Wild-type(WT)mice were divided into WT-Sham group and WT-model group,and HMGB1 knockout(KO)mice were divided into KO-sham group and KO-model group.Sepsis ALI model was established by cecal ligation and perforation in WT-model group and KO-model group.Sham operation was performed in WT-Sham group and KO-Sham group.24 h after modeling,the partial pressure of arterial oxygen(PaO2)was detected,oxy-genation index(OI)was calculated,pathological changes of lung tissue were detected and lung injury score was calculated,the concentrations of tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1 β),interleukin-6(IL-6),reactive oxygen species(ROS),malondialdehyde(MDA),superoxide dismutase(SOD),in serum and lung tissues and the expression of HMGB1,TLR4 and nuclear NF-κB in lung tissues were detected.Results The PaO2,OI and the concentration of SOD in serum and lung tissue of WT-model group were lower than those of WT-Sham group,the lung injury scores,the concentrations of TNF-α,IL-1 β,IL-6,ROS and MDA in serum and lung tissue,and the expression levels of HMGB1,TLR4 and nuclear NF-κB in lung tissue were higher than those in WT-Sham group(P＜0.05).HMGB1 was not expressed in lung tissue of KO-model group,and the concentrations of PaO2,OI and the concentration of SOD in serum and lung tissue of KO-model group were higher than those of WT-model group,the lung injury scores,the concentrations of TNF-α,IL-1β,IL-6,ROS and MDA in serum and lung tissue,and the expression levels of TLR4 and nuclear NF-κB in lung tissue were lower than those of the WT-model group(P＜0.05).Conclusion HMGB1 gene knockout alleviates acute lung injury of sepsis mice,the re-lated molecular mechanism may be the inhibition of TLR4/NF-κB pathway mediated inflammation and oxidative stress.

Gene polymorphisms of CYP2C19,MTHFR,SLCO1B1 and APOE in acute cerebral infarction patients / 国际检验医学杂志

Objective To explore the distribution of CYP2C19,MTHFR,SLCO1B1,and APOE gene poly-morphisms in patients with acute cerebral infarction,so as to provide theoretical basis for individualized drug treatment.Methods A total of 400 patients with acute cerebral infarction admitted to the hospital from 2020 to 2022 were selected as the research subjects,and the polymorphisms of CYP2C19,MTHFR,SLCO1B1 and APOE genes were tested by PCR fluorescene probe method,and the polymorphism distribution of those genes was analyzed.Results In patients with acute cerebral infarction,44.25％of CYP2C19 gene phenotype were EM type,and 9.75％of CYP2C19 gene phenotype were PM type.The proportion of mutations at the C677T locus of the MTHFR gene(CT type+TT type)was 78.50％,CC type accounted for 21.50％.78.75％of the SLCO1B1 genotypes were type Ⅰ wild type,and 1.50％SLCO1B1 gene phenotypes were type Ⅲ homozygous mutant type.The E2 and E3 types accounted for 84.25％of the APOE gene phenotype,while the E4 type ac-counted for 15.75％.Conclusion The distribution of CYP2C19,MTHFR,SLCO1B1 and APOE gene poly-morphisms in 400 acute cerebral infarction patients is analyzed,providing data support for guiding individual-ized medication in the population of acute cerebral infarction patients and of great significance for achieving safe medication.

miR-142-3p inhibits cerulein-induced apoptosis of rat pancreatic exocrine cell line AR42J by regulating Hmgb1 / 基础医学与临床

Objective To investigate the effect of miR-142-3p on the apoptosis of rat pancreatic exocrine cell line AR42J by regulating Hmgb1.Methods AR42J cells were divided into blank group(blank),acute pancreatitis model group(AP,100 nmol/L cerulein for 24 h),and then transfected with miR-142-3p mimics,mimics NC,miR-142-3p inhibitor and inhibitor NC,respectively.The cells in the model group were recorded as miR-142-3p mimics group,mimics NC group,miR-142-3p inhibitor group and inhibitor NC.The expression of miR-142-3p in cells was detected by RT-qPCR.The protein expressions of HMGB1,caspase-3,Bax and Bcl-2 were detected by Western blot.Hoechst staining was used to determine cell apoptosis.The apoptosis rate of cells was detected by flow cytometry.The targeting relationship between miR-142-3p and Hmgb1 was determined by dual luciferase reporter gene assay.Results Compared with blank control group,the expression level of miR-142-3p in the AP group was significantly down-regulated(P＜0.01),the expression level of HMGB1 and caspase-3 proteins was up-regulated(P＜0.05),the expression level of Bax protein was significantly up-regulated(P＜0.01),the expression level of Bcl-2 protein was significantly decreased(P＜0.01)and the apoptosis rate increased significantly(P＜0.01).Compared with the mimics NC group,the level of miR-142-3p in the miR-142-3p mimics group was significantly up-regulated(P＜0.01),the expression of HMGB,caspase-3 and Bax proteins was significantly down-regulated(P＜0.01),the expression of Bcl-2 protein was up-regulated(P＜0.05),and the apoptosis rate decreased signifi-cantly(P＜0.01).Compared with inhibitor NC group,the expression level of miR-142-3p in miR-142-3p inhibitor group was down-regulated(P＜0.05),the expression levels of HMGB1,caspase-3 and Bax proteins were signifi-cantly up-regulated(P＜0.01),the expression level of Bcl-2 protein was decreased(P＜0.05)and the apoptosis rate increased significantly(P＜0.01).The dual luciferase reporter gene assay showed that Hmgb1 was the target gene of miR-142-3p.Conclusions 1)The expression of miR-142-3p was low in the model group.2)miR-142-3p can inhibit the apoptosis of AR42J cells by inhibiting the expression of Hmgb1.

The expression of serum procalcitonin,pentraxin 3 and high mobility group protein B1 in children after open gastrointestinal surgery and its value in predicting early infection / 临床外科杂志

Objectiv To analyze the expression of serum procalcitonin(PCT),pentraxin 3(PTX3)and high mobility group protein B1(HMGB-1)in children after open gastrointestinal surgery and their application value in early infection prediction.Methods A retrospective analysis was performed on 206 children with open gastrointestinal surgery admitted to the hospital from January 2020 to January 2023.They were divided into infection group(27 case)and non-infection group(179 case)according to whether they had postoperative infection.The levels of serum PCT,PTX3 and HMGB-1 before operation,1 d and 3 d after operation were compared between the two groups.The predictive value of single and combined detection of serum indexes 1 d and 3 d after operation for postoperative infection in children with open gastrointestinal surgery was observed.The influencing factors of postoperative infection were analyzed by multivariate Logistic regression.Results The levels of serum PCT,PTX3 and HMGB-1 in the infection group were(2.42±0.39)μg/L,(3.74±0.53)pg/L,(2.07±0.66)p,g/L,(3.06±0.75)μg/L,(18.35±2.74)μg/L,and(26.09±4.16)μg/L at 1 d and 3 d after operation,which were higher than those in the non-infection group(1.71±0.35)pg/L,(2.29±0.36)μg/L,(1.48±0.52)μg/L,(1.73±0.59)pg/L,(13.04±2.26)μg/L,and(15.75±2.83)pg/L(P＜0.05).Receiver operating characteristic curve showed that the area under the curve(AUC)of combined detection of serum PCT,PTX3 and HMGB-1 in predicting postoperative infection in children with open gastrointestinal surgery was the largest(0.989)at 3 days after operation;Multivariate Logistic regression analysis showed that age was an independent protective factor for postoperative infection in children,and Intraoperative blood loss,operation time,serum PCT,PTX3 and HMGB-1 at 1 d and 3 d after operation were independent risk factors(P＜0.05);The levels of serum PCT,PTX3 and HMGB-1 in children with moderate to severe infection were(2.63±0.34)μg/L,(4.12±0.56)μg/L,(2.31±0.69)μg/L,(3.39±0.81)μg/L,(19.86 ±2.91)pg/L,and(28.84±4.40)μg/L at 1 d and 3 d after operation,which were higher than those in children with mild infection(2.11±0.28)μg/L,(3.19±0.49)μg/L,(1.72±0.60)μg/L,(2.58± 0.73)μg/L,(16.15±2.39)μg/L,and(22.09±3.96)pg/L(P＜0.05).Conclusion The expression of serum PCT,PTX3 and HMGB-1 in children after open gastrointestinal surgery was significantly increased,and its expression was related to early postoperative infection and the severity of infection,and the combined predictive value of the three was higher,which could provide reference for early infection prediction.

Correlation of serum RAGE and HMGB1 expression with the occurrence of acute respiratory distress syndrome and IFN-γ/IL-4 ratio in patients with severe pneumonia / 实用医学杂志

Objective To explore the correlation between the expression level of serum Receptor for Advanced Glycation End-Product(RAGE)and High-Mobility Group Protein B1(HMGB1)expression with the occurrence of acute respiratory distress syndrome(ARDS)and interferon-γ/interleukin-4(IFN-γ/IL-4)ratio in patients with severe pneumonia(SP).Methods A prospective investigation was carried out on one hundred children with SP admitted to our hospital from March 2020 to February 2022,and the participants were classified into ARDS group(n = 56)and control group(n = 44)based on the occurrence of secondary ARDS.General informations werec-ollected.The expression of RAGE,HMGB1,IFN-γ and IL-4 in peripheral blood was measured using Enzyme-Linked Immunosorbent Assay(ELISA).Then multivariate Logistic regression analysis was conducted to screen the influencing factors of secondary ARDS in SP children,and the correlation with IFN-γ/IL-4 ratio was verified by pearson correla-tion analysis,moreover,receiver operating characteristic(ROC)curve was plotted to evaluate the value of RAGE and HMGB1 expression in predicting the occurrence of ARDS in SP children.Results There were no statistical difference in gender,age,body temperature and onset season between the two SP groups.The ARDS group had more types of pathogenic bacteria,larger ratio of the partial pressure of oxygen in arterial blood to the inspired oxygen fraction(PaO2/FiO2),higher Acute Physiological Score(APS),and up-regulated expression of RAGE,HMGB1,IFN-γ and IL-4,as well as larger IFN-γ/IL-4 ratio than those of control group,with statistical difference(all P<0.05).Multivariate Logistic regression analysis revealed that pathogen type,PaO2/FiO2 ratio,RAGE,HMGB1,IFN-γ,IL-4 and IFN-γ/IL-4 were the influencing factors for the occurrence of ARDS in children with SP.Pearson correlation test denoted that the serum RAGE and HMGB1 expression levels of SP children were positively correlated with IFN-γ,IL-4 and IFN-γ/IL-4 ratio(P<0.05).ROC curve found that the AUC of serum RAGE and HMGB1 in predicting the occurrence of ARDS in SP children was 0.707 and 0.750,with a sensitivity of 73.2%and 64.3%,and a specificity of 68.2%and 77.3%.The combined test of RAGE and HMGB1 in predicting the occurrence of ARDS in SP children reached an AUC of 0.848,providing a sensitivity and specificity of 80.4%and 81.8%respectively.Conclusions Serum RAGE and HMGB1 expression levels are elevated in SP children with ARDS,and the two are positively correlated with IFN-γ/IL-4 ratio.Therefore,monitoring serum RAGE and HMGB1 expression in children with ARDS secondary to SP has predictive value for the risk of ARDS in SP children.

Study of Lkb1 regulates epithelial regeneration in asthma using airway organoid / 天津医药

Objective To explore the mechanism of Lkb1 regulated epithelial regeneration in asthma by airway organoid culture.Methods Lkb1f/f(the control group,n=10)and Scgb1a1CreER;Lkb1f/fmice(the Lkb1 knockout group,n=9)were taken to establish allergic asthma models by aerosol inhalation of ovalbumin(OVA).Bronchial lavage fluid(BALF)and lung tissue were collected.The number of inflammatory cells in BALF were counted.The amount of CLCA3 positive cells was compared by immunofluorescence staining of lung tissue sections.Club cells were selected by flow cytometry for organoid culture.The average diameter of organoids and organoid formation rate were calculated.Expression levels of goblet cell marker CLCA3,cilia cell markers FOXJ1 and AMPK in Club cells were detected by RT-PCR.Results There were no significant differences in the number of macrophages,eosinophils,neutrophils and lymphocytes in BALF between the control group and the Lkb1 knockout group.The number of CLCA3 positive cells were decreased after Lkb1 knockout.Results of organoid culture showed that the average diameter of organoids derived from Club cells and organoid formation rate were decreased after the absence of Lkb1.The expression of FOXJ1 was reduced.After Lkb1 deletion,the expression of AMPKα in Club cells were decreased and the proliferation of Club cells was inhibited.Activation of AMPK,the downstream signaling pathway of Lkb1,could attenuate the effect of Lkb1 deficiency on the regeneration of Club cells.Conclusion Lkb1 promotes the proliferation of airway progenitor cells by AMPK pathway.

Clinical effect of procaterol hydrochloride combined with Xiaokechuan capsule in the treatment of cough variant asthma and its impact on serological indicators and airway function of children / 新乡医学院学报

Objective To explore the clinical effect of procaterol hydrochloride combined with Xiaokechuan capsule in the treatment of cough variant asthma(CVA)and its impact on serological indicators,airway function of children.Methods A total of 124 children with CVA admitted to the Zigong First People's Hospital from March 2019 to April 2022 were selected as the research subjects.The children were divided into control group and observation group according to random number table method,with 62 cases in each group.The children in the control group were treated with procaterol hydrochloride,and the children in the observation group were treated with procaterol hydrochloride and Xiaokechuan capsule for two weeks.The clinical efficacy of children was compared between the two groups after treatment.The cough scores during the day and night of children were evaluated in the two groups before and 2 weeks after treatment.The serum high mobility group protein B1(HMGB1),Toll like receptor 4(TLR4),nuclear factor-κB(NF-κB),interleukin-4(IL-4),interferon-γ(INF-γ)levels of children in the two groups were measured by enzyme linked immunosorbent assay before and 2 weeks after treatment,and the ratio of INF-γ/IL-was calculated.The 25％maximal expiratory flow-volume(MEF25),50％maximal expiratory flow-volume(MEF50),75％maximal expiratory flow-volume(MEF75)of children in the two groups were measured by lung function detector before and 2 weeks after treatment.The adverse reactions of children in the two groups were recorded during treatment.Results The total effective rate of children in the control group and observation group was 82.26％(51/62)and 95.16％(59/62),respectively;the total effective rate of children in the observation group was significantly higher than that in the control group(P＜0.05).There was no significant difference in cough scores during the day and night of children between the two groups before treatment(P＞0.05);the cough scores during the day and night of children after treatment were significantly lower than those before treatment in the two groups(P＜0.05);after treatment,the cough scores during the day and night of children in the observation group were significantly lower than those in the control group(P＜0.05).There was no significant difference in serum HMGB1,TLR4,NF-κB levels of children between the two groups before treatment(P＞0.05);the serum HMGB1,TLR4,NF-κB levels of children after treatment were significantly lower than those before treatment in the two groups(P＜0.05);after treatment,the serum levels of HMGB1,TLR4,and NF-κB of children in the observation group were significantly lower than those in the control group(P＜0.05).There was no significant difference in MEF25,MEF50,and MEF75 of children between the two groups before treatment(P＞0.05);the MEF25,MEF50,and MEF75 of children after treatment were significantly higher than those before treatment in the two groups(P＜0.05);after treatment,the MEF25,MEF50,and MEF75 of children in the observation group were significantly higher than those in the control group(P＜0.05).There was no significant difference in serum IL-4,INF-γ levels and the ratio of INF-γ/IL-4 of children between the two groups before treatment(P＞0.05);the serum IL-4 level of children after treatment were significantly lower than those before treatment,the INF-γ level and the ratio of INF-γ/IL-4 were significantly higher than those before treatment in the two groups(P＜0.05);after treatment,the serum IL-4 level of children in the observation group was significantly lower than that in the control group,the INF-γ level and the ratio of INF-γ/IL-4 were significantly higher than those in the control group(P＜0.05).All children had good drug tolerance during the treatment period,and no significant adverse drug reactions were observed.Conclusion The combination of Xiaokechuan capsules and procaterol hydrochloride has a significant therapeutic effect for pediatric CVA,and its mechanism of action may be related to the regulation of HMGB1-TLR4-NF-κB signal pathway.

Clinical significance of changes in peripheral blood angiotensin-converting enzyme 2, high mobility group protein B1 and interleukin-33 levels in patients with primary lung cancer complicated by pulmonary infection after surgery / 中国医师进修杂志

Objective:To investigate the changes in peripheral blood angiotensin-converting enzyme 2 (ACE2), high mobility group protein B1 (HMGB1) and interleukin 33 (IL-33) levels and their clinical significance in patients with primary lung cancer complicated by lung infection after surgery.Methods:The clinical data of 92 primary lung cancer patients treated at Longchang People′s Hospital from August 2018 to February 2021 were retrospectively collected, they were underwent radical lung cancer surgery, and were divided into the pulmonary infection group(27 cases) and the non-pulmonary infection group(65 cases) according to whether the patients had postoperative complications of pulmonary infection. The clinical data, peripheral blood ACE2, HMGB1 and IL-33 levels before and after surgery between the two groups were compared. The risk factors associated with postoperative pulmonary infection were analyzed by Lasso regression and Logistic regression. The predictive value of pulmonary infection was analyzed by receiver operating characteristic (ROC) curve. The cut-off values of peripheral blood ACE2, HMGB1 and IL-33 in the ROC curve were used as the boundary to divide the high level group and low level group, and the Kaplan-Meier survival curve was drawn to compare the survival rates of patients with high levels and low levels of peripheral blood ACE2, HMGB1 and IL-33.Results:The incidence of chronic obstructive pulmonary disease in the pulmonary infection group was higher than that in the non-pulmonary infection group: 40.74%(11/27) vs. 15.38%(10/65), there was statistical difference ( χ2 = 6.96, P<0.05). The levels of postoperative peripheral blood ACE2, HMGB1 and IL-33 in the pulmonary infection group were higher than those in the non-pulmonary infection group: (36.87 ± 9.87) mg/L vs. (25.94 ± 8.69) mg/L, (24.49 ± 8.14) μg/L vs. (16.74 ± 5.07) μg/L, (51.48 ± 8.25) ng/L vs. (39.88 ± 6.85) ng/L, there were statistical differences ( P<0.05). The results of Lasso regression and Logistic regression showed that the chronic obstructive pulmonary disease, postoperative peripheral blood ACE2, HMGB1 and IL-33 levels were independent risk factors for postoperative complications of pulmonary infection in patients with primary lung cancer ( P<0.05). The results of ROC curve showed that the area under the curve(AUC) values for postoperative peripheral blood ACE2, HMGB1 and IL-33 levels predicting postoperative complications of lung infection were 0.705, 0.821 and 0.768, respectively, and the AUC for the combination was 0.935. The risk of death in patients with high levels of postoperative peripheral blood ACE2, HMGB1 and IL-3 were 7.500, 4.874 and 2.857 times than the patients with low levels. Conclusions:Postoperative peripheral blood ACE2, HMGB1 and IL-3 levels in patients with primary lung cancer are important factors for pulmonary infection, which can be used for early prediction and evaluation after operation.

Experimental Study on Regulation of Nrf2/HO-1 by Linalool to Inhibit Hepatic Injury Induced by Aflatoxin B1 / 中国实验方剂学杂志

ObjectiveTo investigate the effect of linalool against acute liver injury induced by aflatoxin B1（AFB1） in rats and explore its protective mechanism. MethodTwenty male SPF SD rats were randomly divided into three groups： Control （n=6）， AFB1 （n=7）， and linalool （n=7） groups. Linalool solution （200 mg·kg-1） was administered preventatively for 14 days， while the control and AFB1 groups intragastrically received an equivalent volume of double distilled water. After preventative administration of linalool， AFB1 solution （1 mg·kg-1， dissolved in saline） was intraperitoneally injected for two consecutive days to induce acute liver injury in rats. Samples were collected and processed 14 days after model establishment. Pathological changes in liver tissue of rats were observed using Hematoxylin-eosin（HE） staining and Masson staining. Biochemical detection was performed to measure the levels of alanine transaminase（ALT）， aspartate transaminase（AST）， γ-glutamyl transferase（GGT）， lactate dehydrogenase（LDH）， alkaline phosphatase（ALP）， total bilirubin（TBil）， direct bilirubin（DBil）， indirect bilirubin（IBil）， malondialdehyde（MDA）， superoxidedismutase（SOD）， catalase（CAT） ， glutathione（GSH）， Fe3+， and Fe2+ in the liver tissue. Western blot was adopted to assess protein expression levels of nuclear factor-erythroid 2-related factor 2（Nrf2） and heme oxygenase-1（HO-1）. Molecular docking was performed to verify the binding between linalool and key proteins of the Nrf2/HO-1 signaling pathway. Molecular dynamics techniques were used to confirm the stability and affinity of linalool binding with key proteins of the Nrf2/HO-1 signaling pathway. ResultPathological results showed that compared to that in the AFB1 group， the liver structure in the linalool group tended to be normal， with a significant decrease in blue collagen fibers. The linalool group exhibited significantly reduced levels of ALT， AST， GGT， LDH， ALP， TBil， DBil， and IBil （P<0.01）， Fe3+ and Fe2+ content， and oxidative stress marker MDA （P<0.01）. The levels of antioxidants SOD， CAT， and GSH significantly increased （P<0.01）. Molecular docking showed a molecular docking energy between linalool and Nrf2 and HO-1 targets of -5.495 6 and -5.199 4 kcal·mol-1（1 cal≈4.186 J）， respectively. Molecular dynamics results indicated strong affinity in the binding of linalool with Nrf2 and HO-1. Western blot revealed a significant increase in Nrf2 protein expression （P<0.05） and a decrease in HO-1 protein expression （P<0.01） in the linalool group. ConclusionLinalool may protect against AFB1-induced acute liver injury by modulating the Nrf2/HO-1 ferroptosis signaling pathway to inhibit liver cell ferroptosis and regulate hepatic oxidative stress levels.

Effect of oxymatrine on Cryptosporidium parvum infection in mice based on the HMGB1-TLR2/TLR4-NF-κB pathway / 中国血吸虫病防治杂志

Objective To investigate the involvement of the high mobility group box protein B1 (HMGB1)-Toll-like receptor 2 (TLR2)/TLR4-nuclear factor κB (NF-κB) pathway in the intestinal mucosal injury induced by Cryptosporidium parvum infection, and to examine the effect of oxymatrine (OMT) on C. parvum infection in mice. Methods Forty SPF 4-week-old BALB/c mice were randomly divided into four groups, including the control group, infection group, glycyrrhizin (GA) group and OMT group. Each mouse was orally administered with 1 × 105 C. parvum oocysts one week in the infection, GA and OMT groups following dexamethasone-induced immunosuppression to model C. parvum intestinal infections in mice. Upon successful modeling, mice in the GA group were intraperitoneally injected with GA at a daily dose of 25.9 mL/kg for successive two weeks, and animals in the OMT group were orally administered OMT at a daily dose of 50 mg/kg for successive two weeks, while mice in the control group were given normal food and water. All mice were sacrificed two weeks post-treatment, and proximal jejunal tissues were sampled. The pathological changes of mouse intestinal mucosal specimens were observed using hematoxylin-eosin (HE) staining, and the mouse intestinal villous height, intestinal crypt depth and the ratio of intestinal villous height to intestinal crypt depth were measured. The occludin and zonula occludens protein 1 (ZO1) expression was determined in mouse intestinal epithelial cells using immunohistochemistry, and the relative expression of HMGB1, TLR2, TLR4, myeloid differentiation primary response gene 88 (MyD88) and NF-κB p65 mRNA was quantified in mouse jejunal tissues using quantitative real-time PCR (qPCR) assay. Results HE staining showed that the mouse intestinal villi were obviously atrophic, shortened, and detached, and the submucosal layer of the mouse intestine was edematous in the infection group as compared with the control group, while the mouse intestinal villi tended to be structurally intact and neatly arranged in the GA and OMT groups. There were significant differences among the four groups in terms of the mouse intestinal villous height (F = 6.207, P = 0.000 5), intestinal crypt depth (F = 6.903, P = 0.000 3) and the ratio of intestinal villous height to intestinal crypt depth (F = 37.190, P < 0.000 1). The mouse intestinal villous height was lower in the infection group than in the control group [(321.9 ± 41.1) μm vs. (399.5 ± 30.9) μm; t = 4.178, P < 0.01] and the GA group [(321.9 ± 41.1) μm vs. (383.7 ± 42.7) μm; t = 3.130, P < 0.01], and the mouse intestinal crypt depth was greater in the infection group [(185.0 ± 35.9) μm] than in the control group [(128.4 ± 23.6) μm] (t = 3.877, P < 0.01) and GA group [(143.3 ± 24.7) μm] (t = 2.710, P < 0.05). The mouse intestinal villous height was greater in the OMT group [(375.3 ± 22.9) μm] than in the infection group (t = 3.888, P < 0.01), and there was no significant difference in mouse intestinal villous height between the OMT group and the control group (t = 1.989, P > 0.05). The mouse intestinal crypt depth was significantly lower in the OMT group [(121.5 ± 27.3) μm] than in the infection group (t = 4.133, P < 0.01), and there was no significant difference in mouse intestinal crypt depth between the OMT group and the control group (t = 0.575, P > 0.05). The ratio of the mouse intestinal villous height to intestinal crypt depth was significantly lower in the infection group (1.8 ± 0.2) than in the control group (3.1 ± 0.3) (t = 10.540, P < 0.01) and the GA group (2.7 ± 0.3) (t = 7.370, P < 0.01), and the ratio of the mouse intestinal villous height to intestinal crypt depth was significantly higher in the OMT group (3.1 ± 0.2) than in the infection group (t = 15.020, P < 0.01); however, there was no significant difference in the ratio of the mouse intestinal villous height to intestinal crypt depth between the OMT group and the control group (t = 0.404, P > 0.05). Immunohistochemical staining showed significant differences among the four groups in terms of occludin (F = 28.031, P < 0.000 1) and ZO1 expression (F = 14.122, P < 0.000 1) in mouse intestinal epithelial cells. The proportion of positive occluding expression was significantly lower in mouse intestinal epithelial cells in the infection group than in the control group [(14.3 ± 4.5)% vs. (28.3 ± 0.5)%; t = 3.810, P < 0.01], and the proportions of positive occluding expression were significantly higher in mouse intestinal epithelial cells in the GA group [(30.3 ± 1.3)%] and OMT group [(25.8 ± 1.5)%] than in the infection group (t = 7.620 and 5.391, both P values < 0.01); however, there was no significant differences in the proportion of positive occluding expression in mouse intestinal epithelial cells between the GA or OMT groups and the control group (t = 1.791 and 2.033, both P values > 0.05). The proportion of positive ZO1 expression was significantly lower in mouse intestinal epithelial cells in the infection group than in the control group [(14.4 ± 1.8)% vs. (24.2 ± 2.8)%; t = 4.485, P < 0.01], and the proportions of positive ZO1 expression were significantly higher in mouse intestinal epithelial cells in the GA group [(24.1 ± 2.3)%] (t = 5.159, P < 0.01) and OMT group than in the infection group [(22.5 ± 1.9)%] (t = 4.441, P < 0.05); however, there were no significant differences in the proportion of positive ZO1 expression in mouse intestinal epithelial cells between the GA or OMT groups and the control group (t = 0.037 and 0.742, both P values > 0.05). qPCR assay showed significant differences among the four groups in terms of HMGB1 (F = 21.980, P < 0.000 1), TLR2 (F = 20.630, P < 0.000 1), TLR4 (F = 17.000, P = 0.000 6), MyD88 (F = 8.907, P = 0.000 5) and NF-κB p65 mRNA expression in mouse jejunal tissues (F = 8.889, P = 0.000 7). The relative expression of HMGB1 [(5.97 ± 1.07) vs. (1.05 ± 0.07); t = 6.482, P < 0.05] 、TLR2 [(5.92 ± 1.29) vs. (1.10 ± 0.14); t = 5.272, P < 0.05] 、TLR4 [(5.96 ± 1.50) vs. (1.02 ± 0.03); t = 4.644, P < 0.05] 、MyD88 [(3.00 ± 1.26) vs. (1.02 ± 0.05); t = 2.734, P < 0.05] and NF-κB p65 mRNA [(2.33 ± 0.72) vs. (1.04 ± 0.06); t = 2.665, P < 0.05] was all significantly higher in mouse jejunal tissues in the infection group than in the control group. A significant reduction was detected in the relative expression of HMGB1 (0.63 ± 0.01), TLR2 (0.42 ± 0.10), TLR4 (0.35 ± 0.07), MyD88 (0.70 ± 0.11) and NF-κB p65 mRNA (0.75 ± 0.01) in mouse jejunal tissues in the GA group relative to the control group (t = 8.629, 5.830, 11.500, 4.729 and 6.898, all P values < 0.05), and the relative expression of HMGB1, TLR2, TLR4, MyD88 and NF-κB p65 mRNA significantly reduced in mouse jejunal tissues in the GA group as compared to the infection group (t = 7.052, 6.035, 4.084, 3.165 and 3.274, all P values < 0.05). In addition, the relative expression of HMGB1 (1.14 ± 0.60), TLR2 (1.00 ± 0.24), TLR4 (1.14 ± 0.07), MyD88 (0.96 ± 0.25) and NF-κ B p65 mRNA (1.12 ± 0.17) was significantly lower in mouse jejunal tissues in the OMT group than in the infection group (t = 7.059, 5.320, 3.510, 3.466 and 3.273, all P values < 0.05); however, there were no significant differences between the OMT and control groups in terms of relative expression of HMGB1, TLR2, TLR4, MyD88 or NF-κB p65 mRNA in mouse jejunal tissues (t = 0.239, 0.518, 1.887, 0.427 and 0.641, all P values > 0.05). Conclusions C. parvum infection causes intestinal inflammatory responses and destruction of intestinal mucosal barrier through up-regulating of the HMGB1-TLR2/TLR4-NF-κB pathway. OMT may suppress the intestinal inflammation and repair the intestinal mucosal barrier through inhibiting the activity of the HMGB1-TLR2/TLR4-NF-κB pathway.

Influence of quercetin on aging of bone marrow mesenchymal stem cells induced by microgravity / 中国药理学通报

Aim To investigate the effect of quercetin on the aging model of bone marrow mesenchymal stem cells established under microgravity. Methods Using 3D gyroscope, a aging model of bone marrow mesenchymal stem cells was constructed, and after receiving quercetin and microgravity treatment, the anti-aging effect of the quercetin was evaluated by detecting related proteins and oxidation indexes. Results Compared to the control group, the expressions of age-related proteins p21, pi6, p53 and RB in the microgravity group significantly increased, while the expressions of cyclin D1 and lamin B1 significantly decreased, with statistical significance (P<0.05). In the microgravity group, mitochondrial membrane potential significantly decreased (P<0.05), ROS accumulation significantly increased (P <0.05), SOD content significantly decreased and MDA content significantly increased (P<0.05). Compared to the microgravity group, the expressions of age-related proteins p21, pi6, p53 and RB in the quercetin group significantly decreased, while the expressions of cyclin D1 and lamin B1 significantly increased, with statistical significance (P<0.05). In the quercetin group, mitochondrial membrane potential significantly increased (P<0.05), ROS accumulation significantly decreased (P<0.05), SOD content significantly increased and MDA content significantly decreased (P<0.05). Conclusions Quercetin can resist oxidation, protect mitochondrial function and normal cell cycle, thus delaying the aging of bone marrow mesenchymal stem cells induced by microgravity.

Synthesis and evaluation for anti-HCoV-OC43 activity of novel aloperine derivatives with different core structures / 药学学报

In this study, we designed and synthesized 12 novel aloperine derivatives with different core structures. Among them, compound 3 with a ten-membered ring core was obtained through a special ring expansion reaction after γ-H Huffman elimination of quaternary ammonium salt, and the structure was verified by X-single crystal diffraction. Furthermore, their antiviral activity against human β-coronavirus HCoV-OC43 was evaluated by CCK-8 assay. Quaternary ammonium salt 2a and 3 had a good inhibitory effect against HCoV-OC43, and 2a had the highest anti-HCoV-OC43 activity with an EC50 values of 3.77 μmol·L-1 and a SI value of over 53.1. Schrӧdinger molecular docking results showed that both 2a and 3 might display their anti-HCoV-OC43 activity by directly acting on host TMPRSS2 and SR-B1. The results expanded the structural types of endocyclic aloperine and the function against coronavirus, and provided useful scientific data for the development of pharmaceutical applications of these compounds.

Improvement effect and mechanism of “Layers adjusting external application”paste on synovial fibrosis in rats with knee osteoarthritis / 中国药房

OBJECTIVE To investigate the improvement effect and potential mechanism of “Layers adjusting external application” paste on synovial fibrosis （SF） in rats with knee osteoarthritis （KOA）. METHODS Male SD rats were randomly divided into sham operation group， KOA group and Layers adjusting external application group， with 8 rats in each group. KOA model was induced by the anterior cruciate ligament disruption method in KOA group and Layers adjusting external application group. Fourteen days after modeling， the Layers adjusting external application group was given “Layers adjusting external application” paste [Sanse powder （8 g for every 100 cm2）， Compound sanhuang ointment （5 g for every 100 cm2）] on the knee joint， 8 h every day， for 28 d in total. After the last administration， the degree of synovitis and fibrosis in rats was observed， and Krenn scoring was performed in each group. The expressions of collagen Ⅰ， high mobility group protein B1 （HMGB1） and phosphorylated nuclear factor-κB p65 （p-NF-κB p65） were detected in the synovial membrane； the contents of interleukin-1β （IL- 1β）， IL-6 and tumor necrosis factor-α （TNF-α） in serum as well as the expressions of fibrosis-related and HMGB1/Toll-like receptor 4 （TLR4）/NF-κB signaling pathway-related proteins and mRNA were detected in synovial tissue. RESULTS Compared with the sham operation group， the synovial lining cells in the KOA group showed significant proliferation and disordered arrangement， the inflammatory cell infiltration and collagen fiber deposition were obvious； the positive expressing cells of collagen Ⅰ， HMGB1 and p-NF-κB p65 were increased significantly； the contents of IL-1β， IL-6 and TNF-α in serum， the expressions of fibrosis-related protein （transforming growth factor-β， collagen Ⅰ， tissue inhibitor of metalloproteinase 1， α-smooth muscle actin） and their mRNA as well as theexpressions of HMGB1， TLR4 protein and their mRNA， the expressions of p-NF-κB p65 protein and NF-κB p65 mRNA were all increased significantly in synovial tissues of rats （P＜0.01）. Compared with the KOA group， the pathological changes in the synovial tissue of rats in Layers adjusting external application group were significantly improved， and the above quantitative indicators were significantly reversed （P＜0.05 or P＜0.01）. CONCLUSIONS “Layers adjusting external application” paste could significantly improve SF in KOA rats， the mechanism of which may be associated with the inhibition of the activation of HMGB1/ TLR4/NF-κB signaling pathway.

Effects of Lacticaseibacillus paracasei Shirota Supplementation on Growth Performance, Intestinal Health, and Fecal AFB1 Metabolite in AFB1-Exposed Rats (Kesan Pemberian Lacticaseibacillus paracasei Shirota terhadap Prestasi Pertumbuhan, Kesihatan Usus dan Metabolit AFB1 di dalam Najis Tikus Terdedah AFB1) / Jurnal Sains Kesihatan Malaysia

@#Aflatoxin B1 (AFB1) is a toxin produced by Aspergillus species of fungi. Findings in the literature has shown the potential of probiotic treatment to alleviate AFB1 toxicity. This study explores the effects of Lacticaseibacillus paracasei Shirota (LcS) supplementation on the growth performance, intestinal health, and excretion of faecal AFB1 metabolite of AFB1- exposed rats. Thirty-two male Sprague Dawley rats were divided into control, AFB1, AFB1+LcS and LcS groups. AFB1 was given at a complete dosage of 25 µg AFB1/kg body weight, while LcS supplementation at 2×109 CFU/mL per day for four weeks. The average body weight of the AFB1 group showed no significant increase from week 2 to 4, while other groups had an increment throughout the study. The food intake of the AFB1 and AFB1+LcS groups had significantly reduced throughout the treatment period. AFB1 exposure caused several changes in the histomorphometry parameters but was normalised with LcS supplementation. The AFB1 group showed mild to moderate inflammation in all intestinal parts, whereas only mild inflammation was observed in the jejunum and ileum of the AFB1+LcS group. Faecal Bifidobacterium spp. counts showed an increment in three groups, while the AFB1 group showed a significant reduction. The faecal AFB1 in the AFB1 group was significantly lower than in the AFB1+LcS group. In conclusion, AFB1 affected growth performance and intestinal health, and wherein the effects were alleviated by LcS supplementation. Further investigation on intestinal permeability and serum and urinary AFB1 level is suggested to understand the mechanism of probiotic-AFB1 interaction in alleviating AFB1 toxicity.

Ameliorative effects of Lactobacillus against Aflatoxin B1

Abstract Lactobacilli are probiotics with Aflatoxin (AF) detoxification ability, found in fermented products, GIT of animals and environment. Purpose of this study was to investigate the ability of broiler isolates of Lactobacillus against Aflatoxin B1 (AFB1). For this purpose, 5 isolates of Lactobacillus from broiler gut were incubated with 100 ppb AFB1 in aqueous environment and effect of different parameters (cell fractions, time, temperature, pH) on detoxification was determined by HPLC. The ameliorative effect of Lactobacillus salivarius (LS) against AFB1 was studied in broiler. The results revealed that LS (CR. 4) showed the best results (in vitro) as compared to other isolates (L. salivarius (CR. 3, CR, 4), L. agilis (CE. 2.1, CE. 3.1) and L. crispatus (CE. 28). Cell debris of CR. 4 showed significantly higher detoxification (P 0.05). Maximum amount of AFB1 was detoxified at 30°C (97%), pH 4.0 (99%) and 6 h (99.97%). In vivo study showed that AFB1 decreased weight gain (1,269 ± 0.04 gm/ bird), feed consumed (2,161 ± 0.08 gm/ bird), serum total protein (2.42 ± 0.34 gm/ dl), serum albumin (0.5 ± 0.2 2 gm/dl) and antibody titer (4.2 ± 0.83). Liver function enzymes were found (alanine transaminase (ALT): 32 ± 10.7 U/L) and aspartate transaminase (AST): 314.8 ± 27 U/L) elevated in AFB1 fed broilers. Treatment with 1% LS not only decreased the toxic effects of AFB1 (group D) but also improved the overall health of broilers due to its probiotic effects (p 0.05) as compared to control negative (group A). The detoxification ability of LS was better than commercial binder (CB) (0.2% Protmyc). It was concluded that detoxification of AFB1 by Lactobacillus was strain, temperature, pH and time dependent. LS has detoxification ability against AFB1 in vivo.

Resumo Os lactobacilos são probióticos com capacidade de desintoxicação da Aflatoxina (AF), encontrados em produtos fermentados, TGI de animais e meio ambiente. O objetivo deste estudo foi investigar a capacidade de isolados de frango de corte de Lactobacillus contra a Aflatoxina B1 (AFB1). Para tanto, 5 isolados de Lactobacillus de intestino de frango foram incubados com 100 ppb AFB1 em meio aquoso, e o efeito de diferentes parâmetros (frações celulares, tempo, temperatura, pH) na desintoxicação foi determinado por CLAE. O efeito melhorador de Lactobacillus salivarius (LS) contra AFB1 foi estudado em frangos de corte. Os resultados revelaram que LS (CR. 4) apresentou os melhores resultados (in vitro) em comparação com outros isolados [L. salivarius (CR. 3, CR. 4), L. agilis (CE. 2.1, CE. 3.1) e L. crispatus (CE. 28)]. Detritos celulares de CR. 4 mostraram desintoxicação significativamente maior (P 0.05). A quantidade máxima de AFB1 foi desintoxicada a 30 °C (97%), pH 4.0 (99%) e 6 h (99,97%). O estudo in vivo mostrou que AFB1 diminuiu o ganho de peso (1,269 ± 0.04 g / ave), alimento consumido (2,161 ± 0.08 g / ave), proteína total sérica (2.42 ± 0.34 g / dl), albumina sérica (0.5 ± 0.22 gm / dl) e título de anticorpo (4.2 ± 0.83). As enzimas da função hepática foram encontradas (alanina transaminase (ALT): 32 ± 10.7 U / L) e aspartato transaminase (AST): 314.8 ± 27 U / L) elevadas em AFB1 alimentados com frangos. O tratamento com 1% LS não só diminuiu os efeitos tóxicos de AFB1 (grupo D), mas também melhorou a saúde geral dos frangos devido aos seus efeitos probióticos (p 0.05) em comparação com o controle negativo (grupo A). A capacidade de desintoxicação do LS foi melhor do que o aglutinante comercial (CB) (0.2% Protmyc). Concluiu-se que a desintoxicação de AFB1 por Lactobacillus foi dependente da cepa, temperatura, pH e tempo. LS tem capacidade de desintoxicação contra AFB1 in vivo.

Ameliorative effects of Lactobacillus against Aflatoxin B1 / Efeitos benéficos do Lactobacillus contra a Aflatoxin B1

Abstract Lactobacilli are probiotics with Aflatoxin (AF) detoxification ability, found in fermented products, GIT of animals and environment. Purpose of this study was to investigate the ability of broiler isolates of Lactobacillus against Aflatoxin B1 (AFB1). For this purpose, 5 isolates of Lactobacillus from broiler gut were incubated with 100 ppb AFB1 in aqueous environment and effect of different parameters (cell fractions, time, temperature, pH) on detoxification was determined by HPLC. The ameliorative effect of Lactobacillus salivarius (LS) against AFB1 was studied in broiler. The results revealed that LS (CR. 4) showed the best results (in vitro) as compared to other isolates (L. salivarius (CR. 3, CR, 4), L. agilis (CE. 2.1, CE. 3.1) and L. crispatus (CE. 28). Cell debris of CR. 4 showed significantly higher detoxification (P<0.05). Maximum amount of AFB1 was detoxified at 30°C (97%), pH 4.0 (99%) and 6 h (99.97%). In vivo study showed that AFB1 decreased weight gain (1,269 ± 0.04 gm/ bird), feed consumed (2,161 ± 0.08 gm/ bird), serum total protein (2.42 ± 0.34 gm/ dl), serum albumin (0.5 ± 0.2 2 gm/dl) and antibody titer (4.2 ± 0.83). Liver function enzymes were found (alanine transaminase (ALT): 32 ± 10.7 U/L) and aspartate transaminase (AST): 314.8 ± 27 U/L) elevated in AFB1 fed broilers. Treatment with 1% LS not only decreased the toxic effects of AFB1 (group D) but also improved the overall health of broilers due to its probiotic effects (p<0.05) as compared to control negative (group A). The detoxification ability of LS was better than commercial binder (CB) (0.2% Protmyc). It was concluded that detoxification of AFB1 by Lactobacillus was strain, temperature, pH and time dependent. LS has detoxification ability against AFB1 in vivo.

Resumo Os lactobacilos são probióticos com capacidade de desintoxicação da Aflatoxina (AF), encontrados em produtos fermentados, TGI de animais e meio ambiente. O objetivo deste estudo foi investigar a capacidade de isolados de frango de corte de Lactobacillus contra a Aflatoxina B1 (AFB1). Para tanto, 5 isolados de Lactobacillus de intestino de frango foram incubados com 100 ppb AFB1 em meio aquoso, e o efeito de diferentes parâmetros (frações celulares, tempo, temperatura, pH) na desintoxicação foi determinado por CLAE. O efeito melhorador de Lactobacillus salivarius (LS) contra AFB1 foi estudado em frangos de corte. Os resultados revelaram que LS (CR. 4) apresentou os melhores resultados (in vitro) em comparação com outros isolados [L. salivarius (CR. 3, CR. 4), L. agilis (CE. 2.1, CE. 3.1) e L. crispatus (CE. 28)]. Detritos celulares de CR. 4 mostraram desintoxicação significativamente maior (P < 0.05). A quantidade máxima de AFB1 foi desintoxicada a 30 °C (97%), pH 4.0 (99%) e 6 h (99,97%). O estudo in vivo mostrou que AFB1 diminuiu o ganho de peso (1,269 ± 0.04 g / ave), alimento consumido (2,161 ± 0.08 g / ave), proteína total sérica (2.42 ± 0.34 g / dl), albumina sérica (0.5 ± 0.22 gm / dl) e título de anticorpo (4.2 ± 0.83). As enzimas da função hepática foram encontradas (alanina transaminase (ALT): 32 ± 10.7 U / L) e aspartato transaminase (AST): 314.8 ± 27 U / L) elevadas em AFB1 alimentados com frangos. O tratamento com 1% LS não só diminuiu os efeitos tóxicos de AFB1 (grupo D), mas também melhorou a saúde geral dos frangos devido aos seus efeitos probióticos (p < 0.05) em comparação com o controle negativo (grupo A). A capacidade de desintoxicação do LS foi melhor do que o aglutinante comercial (CB) (0.2% Protmyc). Concluiu-se que a desintoxicação de AFB1 por Lactobacillus foi dependente da cepa, temperatura, pH e tempo. LS tem capacidade de desintoxicação contra AFB1 in vivo.

Assessment of aflatoxin B1 contamination in rice and maize / Evaluación de la contaminación por aflatoxina B1 en arroz y maíz

Introduction: Aflatoxins B1 are among the most common poisonous mycotoxins produced by certain fungi that harm animals and crops. Mycotoxins can cause a variety of adverse health effects and pose a serious health threat to humans. The Maximum Residue Limits of aflatoxin B1 in processed cereals and ingredients are 2 parts per billion (ppb) and 5 ppb, respectively. Objectives: To evaluate the status of aflatoxin B1 contamination in rice, corn and staple food produced in Ha Giang province compared with the maximum permitted levels. Methods: A total of 210 rice and maize samples were analyzed to quantify the level of aflatoxin B1. Analysis of mycotoxins was conducted by High Performance Liquid Chromatography using a fluorescence detector. Results: It was found that rice, rice products, maize, and maize products had a mean aflatoxin B1 content of 1.79 ppb, 2.55 ppb, 2.19 ppb, and 6.35 ppb, respectively. The results also showed that 71.9 percent of samples were contaminated with mycotoxins, and 14.28 percent of samples exceeded the maximum allowable limit. Conclusion: The concentration of aflatoxin B1 in 14.28 percent of the samples are over permissible limits by nationwide regulations (AU)

Introducción: La aflatoxina B1 se encuentra entre las micotoxinas más comunes y venenosas producidas por ciertos hongos que dañan a los animales y los cultivos. Las micotoxinas pueden causar una variedad de efectos adversos para la salud y representar una grave amenaza para la salud de los seres humanos. Los límites máximos de residuos de aflatoxina B1en cereales e ingredientes procesados son de 2 ppb y 5 ppb, respectivamente. Objetivos: Evaluar el estado de contaminación por aflatoxina B1 en arroz, maíz y alimentos básicos producidos en la provincia de Ha Giang, en comparación con los niveles máximos permitidos. Métodos: Se analizaron un total de 210 muestras de arroz y maíz para cuantificar el nivel de aflatoxina B1. El análisis de micotoxinas se realizó mediante cromatografía líquida de alta resolución, utilizando un detector de fluorescencia. Resultados: Se encontró que el arroz, los productos de arroz, el maíz y los productos de maíz tenían un contenido medio de aflatoxin B1, de 1,79 ppb, 2,55 ppb, 2,19 ppb y 6,35 ppb, respectivamente. Los resultados también mostraron que el 71,9 por ciento de las muestras estaban contaminadas con micotoxinas y el 14,28 por ciento de las muestras excedieron el límite máximo permitido. Conclusión: La concentración de aflatoxina B1 en el 14,28 por ciento de las muestras está por encima de los límites permisibles por la norma nacional(AU)

Lamin B1 regulates the growth of hepatocellular carcinoma cells by influencing telomerase activity / 生物工程学报

Lamin B1 (LMNB1) is highly expressed in liver cancer tissues, and its influence and mechanism on the proliferation of hepatocellular carcinoma cells were explored by knocking down the expression of the protein. In liver cancer cells, siRNAs were used to knock down LMNB1. Knockdown effects were detected by Western blotting. Changes in telomerase activity were detected by telomeric repeat amplification protocol assay (TRAP) experiments. Telomere length changes were detected by quantitative real-time polymerase chain reaction (qPCR). CCK8, cloning formation, transwell and wound healing were performed to detect changes in its growth, invasion and migration capabilities. The lentiviral system was used to construct HepG2 cells that steadily knocked down LMNB1. Then the changes of telomere length and telomerase activity were detected, and the cell aging status was detected by SA-β-gal senescence staining. The effects of tumorigenesis were detected by nude mouse subcutaneous tumorigenesis experiments, subsequent histification staining of tumors, SA-β-gal senescence staining, fluorescence in situ hybridization (FISH) for telomere analysis and other experiments. Finally, the method of biogenesis analysis was used to find the expression of LMNB1 in clinical liver cancer tissues, and its relationship with clinical stages and patient survival. Knockdown of LMNB1 in HepG2 and Hep3B cells significantly reduced telomerase activity, cell proliferation, migration and invasion abilities. Experiments in cells and tumor formation in nude mice had demonstrated that stable knockdown of LMNB1 reduced telomerase activity, shortened telomere length, senesced cells, reduced cell tumorigenicity and KI-67 expression. Bioinformatics analysis showed that LMNB1 was highly expressed in liver cancer tissues and correlated with tumor stage and patient survival. In conclusion, LMNB1 is overexpressed in liver cancer cells, and it is expected to become an indicator for evaluating the clinical prognosis of liver cancer patients and a target for precise treatment.

A hnRNPA2B1 agonist effectively inhibits HBV and SARS-CoV-2 omicron in vivo

The twenty-first century has already recorded more than ten major epidemics or pandemics of viral disease, including the devastating COVID-19. Novel effective antivirals with broad-spectrum coverage are urgently needed. Herein, we reported a novel broad-spectrum antiviral compound PAC5. Oral administration of PAC5 eliminated HBV cccDNA and reduced the large antigen load in distinct mouse models of HBV infection. Strikingly, oral administration of PAC5 in a hamster model of SARS-CoV-2 omicron (BA.1) infection significantly decreases viral loads and attenuates lung inflammation. Mechanistically, PAC5 binds to a pocket near Asp49 in the RNA recognition motif of hnRNPA2B1. PAC5-bound hnRNPA2B1 is extensively activated and translocated to the cytoplasm where it initiates the TBK1-IRF3 pathway, leading to the production of type I IFNs with antiviral activity. Our results indicate that PAC5 is a novel small-molecule agonist of hnRNPA2B1, which may have a role in dealing with emerging infectious diseases now and in the future.