Molecular targets and mechanisms of Jiawei Jiaotai Pill on diabetic cardiomyopathy based on network pharmacology

BACKGROUND Jiawei Jiaotai Pill is commonly used in clinical practice to reduce apoptosis,increase insulin secretion,and improve blood glucose tolerance.However,its mechanism of action in the treatment of diabetic cardiomyopathy(DCM)remains unclear,hindering research efforts aimed at developing drugs specifically for the treatment of DCM.AIM To explore the pharmacodynamic basis and molecular mechanism of Jiawei Jiaotai Pill in DCM treatment.METHODS We explored various databases and software,including the Traditional Chinese Medicine Systems Pharmacology Database,Uniport,PubChem,GenCards,String,and Cytoscape,to identify the active components and targets of Jiawei Jiaotai Pill,and the disease targets in DCM.Protein-protein interaction network,gene ontology,and Kyoto Encyclopedia of Genes and Genomes analyses were used to determine the mechanism of action of Jiawei Jiaotai Pill in treating DCM.Molecular docking of key active components and core targets was verified using AutoDock software.RESULTS Total 42 active ingredients and 142 potential targets of Jiawei Jiaotai Pill were identified.There were 100 common targets between the DCM and Jiawei Jiaotai Pills.Through this screening process,TNF,IL6,TP53,EGFR,INS,and other important targets were identified.These targets are mainly involved in the positive regulation of the mitogen-activated protein kinase(MAPK)MAPK cascade,response to xenobiotic stimuli,response to hypoxia,positive regulation of gene expression,positive regulation of cell proliferation,negative regulation of the apoptotic process,and other biological processes.It was mainly enriched in the AGE-RAGE signaling pathway in diabetic complications,DCM,PI3K-Akt,interleukin-17,and MAPK signaling pathways.Molecular docking results showed that Jiawei Jiaotai Pill's active ingredients had good docking activity with DCM's core target.CONCLUSION The active components of Jiawei Jiaotai Pill may play a role in the treatment of DCM by reducing oxidative stress,cardiomyocyte apoptosis and fibrosis,and maintaining metabolic homeostasis.

Comparing the precision of the pSOFA and SIRS scores in predicting sepsis-related deaths among hospitalized children:a multi-center retrospective cohort study

BACKGROUND:The latest sepsis definition includes both infection and organ failure,as evidenced by the sequential organ failure assessment(SOFA)score.However,the applicability of the pediatric SOFA score(pSOFA)is not yet determined.This study evaluated the effectiveness of both pSOFA and system inflammatory reaction syndrome(SIRS)scores in predicting sepsis-related pediatric deaths.METHODS:This is a retrospective multi-center cohort study including hospitalized patients<18 years old with diagnosed or not-yet-diagnosed infections.Multivariate analyses were carried out to evaluate risk factors for in-hospital mortality.According to Youden index(YI),three sub-categories of pSOFA were screened out and a new simplified pSOFA score(spSOFA)was formed.The effectiveness and accuracy of prediction of pSOFA,SIRS and spSOFA was retrieved from the area under the receiver operating characteristic curve(AUROC)and Delong’s test.RESULTS:A total of 1,092 participants were eligible for this study,and carried a 23.4%in-hospital mortality rate.The 24-h elevated pSOFA score(24 h-pSOFA),bloodstream infection,and mechanical ventilation(MV)requirement were major risk factors associated with sepsis-related deaths.The AUROC analysis confirmed that the spSOFA provided good predictive capability in sepsis-related pediatric deaths,relative to the 24 h-pSOFA and SIRS.CONCLUSIONS:The pSOFA score performed better than SIRS in diagnosing infected children with high mortality risk.However,it is both costly and cumbersome.We,therefore,proposed spSOFA to accurately predict patient outcome,without the disadvantages.Nevertheless,additional investigations,involving a large sample population,are warranted to confirm the conclusion of this study.

Efficacy of HA330-II column hemoadsorption in Epstein-Barr virusassociated hemophagocytic lymphohistiocytosis combined with liver failure:A case report

BACKGROUND Hemophagocytic lymphohistiocytosis(HLH)is a severe and potentially deadly condition associated with extensive inflammation and immune activation.Cytokine adsorption may serve as a supportive treatment that can stabilize organ function in affected patients by reducing their circulating cytokines levels.To date,no descriptions of clinical experiences associated with the use of HA330-II column hemoadsorption for the treatment of children affected by HLH have been published.CASE SUMMARY We describe the case of an 11-year-old child with Epstein-Barr virus-associated HLH complicated by liver failure.She underwent HA330-II column hemoadsorption and chemotherapy and exhibited reductions in levels of inflammatory cytokines,including interleukin(IL),IL-6,IL-8,IL-10,and interferon-γ.The patient’s condition and laboratory parameters gradually improved with treatment.CONCLUSION Hemoadsorption may play an important role in cytokine storm elimination in children with HLH combined with liver failure and consequent multiple organ failure.

Role of Glutamine in the Mediation of E-cadherin, p120-catenin and Inflammation in Ventilator-induced Lung Injury

Background： Ventilator-induced lung injury （VILI） is commonly associated with barrier dysfunction and inflammation reaction. Glutamine could ameliorate VILI, but its role has not been fully elucidated, This study examined the relationship between inflammatory cytokines （interleukin JILl-6, tumor necrosis factor [TNF]-α, and IL-10） and adherens junctions （E-cadherin, p 120-catenin）, which were ameliorated by glutamine in VILI, both in vitro and in vivo. Methods： For the in vivo study, 30 healthy C57BL/6 mice weighing 25-30 g were randomly divided into five groups with random number table （n = 6 in each group）： control （Group C）; low tidal volume （Group L）; low tidal volume ＋ glutamine （Group L ＋ G）; high tidal volume （Group H）; and high tidal volume ＋ glutamine （Group H ＋ G）. Mice in all groups, except Group C, underwent mechanical ventilation for 4 h. For the in vitro study, mouse lung epithelial 12 （MLE- 12） cells pretreated with glutamine underwent cyclic stretching at 20% for 4 h. Cell lysate and lung tissue were obtained to detect the junction proteins, inflammatory cytokines, and lung pathological changes by the Western blotting, cytokine assay, hematoxylin and eosin staining, and immunofluorescence. Results： In vivo, compared with Group C, total cell counts （t= -28.182, P 〈 0.01）, the percentage of neutrophils （t = -28.095, P 〈 0.01）, IL-6 （t = -28.296, P 〈 0.01 ）, and TNF-α（t = - 19.812, P 〈 0.01 ） in bronchoalveolar lavage （BAL） fluid, lung injury scores （t = -6.708, P 〈 0.01）, and the wet-to-dry ratio （t = - 15.595, P 〈 0.01 ） were increased in Group H; IL- 10 in BAL fluid （t = 9.093, P 〈 0.01 ） and the expression of E-cadherin （t= 10.044, P 〈 0.01） and p120-catenin （t = 13.218, P 〈 0.01） were decreased in Group H. Compared with Group H, total cell counts （t - 14.844, P 〈 0.01 ）, the percentage of neutrophils （t = 18.077, P 〈 0.0 l ）, IL-6 （t - 18.007, P 〈 0.01 ）, and TNF-α （t =1 0.171, P 〈 0.01 ） in BAL fluid were decreased in Group H ＋ G; IL-10 in BAL fluid （t - -7.531, P 〈 0.01 ） and the expression of E-cadherin （t = - 14.814, P 〈 0.01 ） and p 120-catenin （t = -9.114, P 〈 0.01 ） were increased in Group H ＋ G. In vitro, compared with the nonstretching group, the levels of IL-6 （t = 21.111, P 〈 0.01 ） and TNF-α （t - 15.270, P 〈 0.01 ） were increased in the 20% cyclic stretching group; the levels of IL- 10 （t = 5.450, P 〈 0.01 ） and the expression of E-cadherin （t = 17.736, P 〈 0.01 ） and p 120-catenin （t = 16.136, P 〈 0.01 ） were decreased in the 20% cyclic stretching group. Compared with the stretching group, the levels of IL-6 （t = 11.818, P 〈 0.01） and TNF-α （t = 8.631, P 〈 0.01 ） decreased in the glutamine group; the levels of IL- 10 （t = 3.203, P 〈 0.05） and the expression of E-cadherin （t= 13.567, P 〈 0.01） and p 120-catenin （t = -10.013, P 〈 0.01） were increased in the glutamine group. Conclusions： High tidal volume mechanical ventilation and 20% cyclic stretching could cause VIM. Glutamine regulates VIM by improving cytokines and increasing the adherens junctions, protein E-cadherin and p 120-catenin, to enhance the epithelial barrier function.

Laser irradiation of graphite foils as robust current collectors for high-mass loaded electrodes of supercapacitors

Conductive substrates with low cost,lightweight,and chemical stability have been highly recognized as alternative current collectors for energy storage devices.Graphite foil is promising to fulfill these requests,whereas the inert surface chemistry denies its possibility as the carrier with high-mass loading active species.Herein,we report a facile yet efficient laser-mediated strategy to fast regulate graphite foils for robustly loading active species.The smooth and hydrophobic graphite foil surface turned to be a rough,super-hydrophilic one containing oxygen-rich clusters after lasering.The reconstructed surface affords anchors for active species,such as nanostruetured MnO_(2),FeOOH,and Fe_(2)O_(3),with the highest loading mass of 20 mg·cm^(-2).The high-mass loading MnO_(2)electrode offers an areal capacitance of 3933 mF·cm^(-2)at 1 mA·cm^(-2).Then,the asymmetric supercapacitor,fabricated by MnO_(2)and Fe_(2)O_(3)deposited laser-irradiated graphite foils,exhibits improved performance with high energy density,large power capability,and long-term stability.The strategy suggests a reliable way to produce alternative current collectors for robust energy storage devices.