Jatonik polyherbal mixture induced rat liver MMPT pore opening in normal Wistar rat: In vitro and in vivo studies / 中草药·英文版

OBJECTIVE@#To assess acute toxicity, the in vitro and in vivo effects of methanol and ethyl acetate extracts (JME and JEE) of Jatonik polyherbal mixture on some mitochondria-related parameters and their effect on the activity of some liver enzymes.@*METHODS@#Acute toxicity of JME and JEE was determined using Lorke's method. In vitro and in vivo opening of the mitochondrial membrane permeability transition pore (MMPT pore) was spectrophotometrically assayed. Production of malondialdehyde (MDA) as an index of lipid peroxidation and the activity of mitochondrial ATPase was evaluated in vitro and in vivo and the effect of JME and JEE on the activity of liver enzymes such as alkaline phosphatase (ALP), aspartate and alanine aminotransferase (AST and ALT) and gamma-glutamyl transferase (GGT) was also investigated.@*RESULTS@#JME had an LD50 of 3 808 mg/kg b.w whereas JEE had an LD50 greater than 5 000 mg/kg b.w. of rats. After the rats have been fed with both extracts, a photomicrograph of a piece of liver tissue showed no apparent symptoms of toxicity. From the in vitro and in vivo studies, both extracts prompted intact mitochondria to open their MMPT pores. When compared to the control, lipid peroxide product release and ATPase activity were significantly increased (P < 0.05) in vitro and in vivo. The activities of AST, ALT, and GGT were all reduced at 50 mg/kg when treated with JME, but the activity of AST was considerably enhanced when treated with JEE (P < 0.05). The results revealed that both JME and JEE of the Jatonik polyherbal mixture had low toxicity, profound MMPTpore induction, and enhanced ATPase activity, but an increased MDA production.@*CONCLUSION@#Jatonik extracts may be a promising target for drug development in diseases where there is dysregulation of apoptosis, however, further studies are needed to better clarify the molecular mechanism involved in these phenomena.

Quercetin Alleviates Lipopolysaccharide-Induced Cardiac Inflammation via Inhibiting Autophagy and Programmed Cell Death / 生物医学与环境科学（英文）

OBJECTIVE@#The aim of this study is to explore the potential modulatory role of quercetin against Endotoxin or lipopolysaccharide (LPS) induced septic cardiac dysfunction.@*METHODS@#Specific pathogen-free chicken embryos ( n = 120) were allocated untreated control, phosphate buffer solution (PBS) vehicle, PBS with ethanol vehicle, LPS (500 ng/egg), LPS with quercetin treatment (10, 20, or 40 nmol/egg, respectively), Quercetin groups (10, 20, or 40 nmol/egg). Fifteen-day-old embryonated eggs were inoculated with abovementioned solutions via the allantoic cavity. At embryonic day 19, the hearts of the embryos were collected for histopathological examination, RNA extraction, real-time polymerase chain reaction, immunohistochemical investigations, and Western blotting.@*RESULTS@#They demonstrated that the heart presented inflammatory responses after LPS induction. The LPS-induced higher mRNA expressions of inflammation-related factors (TLR4, TNFα, MYD88, NF-κB1, IFNγ, IL-1β, IL-8, IL-6, IL-10, p38, MMP3, and MMP9) were blocked by quercetin with three dosages. Quercetin significantly decreased immunopositivity to TLR4 and MMP9 in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of TLR4, IFNγ, MMP3, and MMP9 when compared with the LPS group. Quercetin treatment prevented LPS-induced increase in the mRNA expression of Claudin 1 and ZO-1, and significantly decreased protein expression of claudin 1 when compared with the LPS group. Quercetin significantly downregulated autophagy-related gene expressions (PPARα, SGLT1, APOA4, AMPKα1, AMPKα2, ATG5, ATG7, Beclin-1, and LC3B) and programmed cell death (Fas, Bcl-2, CASP1, CASP12, CASP3, and RIPK1) after LPS induction. Quercetin significantly decreased immunopositivity to APOA4, AMPKα2, and LC3-II/LC3-I in the treatment group when compared with the LPS group. Quercetin significantly decreased protein expressions of AMPKα1, LC3-I, and LC3-II. Quercetin significantly decreased the protein expression to CASP1 and CASP3 by immunohistochemical investigation or Western blotting in treatment group when compared with LPS group.@*CONCLUSION@#Quercetin alleviates cardiac inflammation induced by LPS through modulating autophagy, programmed cell death, and myocardiocytes permeability.

Study on the stability and H+ permeable membrane properties of polymersomes / 药学实践杂志

Objective To prepare polymersomes (PSs) by block copolymers，evaluate their membrane structural stability，investigate the H+ transmembrane permeability of PSs and the impact of 1,4-dioxane and establish a foundation for drug encapsulation within polymersomes. Methods PSs were self-assembled by a block copolymer, PEG-PLGA, in a solvent solution. The pH-sensitive fluorescence probe HPTS was employed to examine the H+ transmembrane properties of PSs and compare them with PSs prepared using PBD-b-PEO, PS-b-PEO, and liposomes. The effect of varying concentrations of 1,4-dioxane on PSs’ membrane permeability properties was also investigated. Results The fluorescence excitation spectra of HPTS exhibited pH dependency, which showed a linear correlation between extravesicular H+ concentration and t1/2. Significant differences were observed in the membrane permeability capabilities of PSs with different membrane wall thicknesses. Compared to liposomes, the H+ transmembrane coefficients for the three types of PSs were reduced by 2.39×104, 3.38×104, and 5.48×108 times, respectively. 1,4-dioxane was found to modulate the permeability of PSs’ membranes, which displayed a concentration-dependent relationship. Conclusion PSs exhibited significantly lower membrane permeability compared to liposomes, indicating superior stability. 1,4-dioxane was identified as a modulator of PSs’ permeability, which offered potential for drug loading and release within PSs.

Effects of the application of sodium ascorbate after in-office bleaching on the penetration of hydrogen peroxide, color change, and microtensile bond strength

Abstract This study aimed to evaluate the effects of the application of 10% sodium ascorbate (SA) after in-office bleaching on the penetration of hydrogen peroxide (HP) into the pulp chamber, color change, and microtensile bond strength (µTBS) to the resin-enamel interface. Thirty premolars and thirty molars were randomly divided into three groups (n = 20 each). One group was exposed to deionized water (negative control). The other two groups were bleached with 35% HP in a single session for 3x15 minutes for each application. However, in only one of them, SA was applied for 10 minutes after bleaching. After, the concentration (µg/mL) of HP in each pulp chamber was evaluated by UV-Vis spectrophotometry. Color changes (ΔEab, ΔE00, and ΔWID) were evaluated with a digital spectrophotometer before and in the first week after bleaching. After treatment, molars were restored and sectioned to obtain resin-enamel interface sticks for µTBS at a crosshead speed of 1 mm/min until failure. The HP concentration and µTBS data were analyzed using one-way ANOVA and Tukey tests, and color changes were analyzed by t-tests (α = 0.05). SA application significantly improved the µTBS values and reduced the HP concentrations within the pulp chambers (p < 0.0001). The application of SA significantly interfered with the color changes after bleaching when compared to the control group (p < 0.05). Application of 10% SA after in-office bleaching successfully reduced the penetration of HP into the pulp chamber; however, it decreased color change.

Resumo Este estudo teve como objetivo avaliar os efeitos da aplicação do ascorbato de sódio a 10% (AS) depois do clareamento em consultório na penetração do peróxido do hidrogênio (PH) na câmara pulpar, mudança de cor e resistência de união (RU) da interface resina-esmalte. Trinta pré-molares e trinta molares foram divididos aleatoriamente em três grupos (n = 20). Um grupo foi exposto em água deionizada (controle negativo). Os outros dois grupos foram clareados com 35% PH numa única sessão de 3x15 minutos para cada aplicação. Porém, só um grupo recebeu AS durante 10 minutos depois do clareamento. Depois, a concentração (µg/mL) do PH no interior de cada câmara pulpar foi avaliado com espectrofotometria UV-Vis. A mudança de cor (ΔEab, ΔE00 and ΔWID) foi avaliada como espectrofotômetro digital antes e depois de uma semana do clareamento. Após de cada tratamento, os molares foram restaurados e seccionados em espécimes com interface resina-esmalte para o teste de RU por microtração a uma velocidade de 1 mm/min até a fratura. Os dados da concentração de PH e RU foram analisados usando ANOVA de uma via e teste de Tukey, e a mudança de cor com o teste t (α = 0.05). A aplicação de AS melhorou significativamente a RU e reduziu a concentração de PH na câmara pulpar (p < 0.0001). A aplicação de AS interferiu significativamente na mudança de cor depois do clareamento comprado com o grupo controle (p < 0.05). A aplicação de SA a 10% depois do clareamento em consultório reduziu significativamente a penetração do PH na câmara pulpar e interferiu na mudança de cor.

Análisis bidimensional de la permeabilidad de vías aéreas con el tamaño de senos maxilares y su relación con el desarrollo de la clase esqueletal en una población mexicana / Two-dimensional analysis of airway permeability with maxillary sinus size and its relationship with the development of skeletal class in a Mexican population

Comparar la permeabilidad de las vías aéreas y el tamaño de los senos maxilares en relación con la clase esqueletal. se midieron 90 radiografías lateral de cráneo, divididas en 3 grupos, comparando las 3 clases esqueletales, las cuales se determinaron con la medida ANB de Steiner, y estas a su vez en dos subgrupos que fueron hombres y mujeres, en las cuales se utilizó el análisis de McNamara para el análisis de vías aéreas y para el área del seno maxilar se tomaron dos medidas una antero-posterior y cefálica-caudal. Al comparar los hombres con las mujeres se identificó significancia estadística en vía área superior de clase II (p=≤0.017), vía aérea inferior de clase III (p=≤0.006). Al comparar las clases esqueletales en hombres se identificó diferencias en la vía aérea superior en las clases I vs III (p=≤0.05), inferior en la clase I vs III (p=≤0,001) y II vs III (p=≤0.044). Con respecto a mujeres se identificó significancia en la vía aérea superior al comparar la clase I vs II (p=≤0,043), vía aérea inferior en la clase II vs III (p=≤0.05), longitud del seno maxilar al comparar clase I vs II (p=≤0.017). Entre la clase I esqueletal y la clase II, el tamaño de los senos maxilares resulto menor en longitud en las mujeres de clase II esqueletal. Entre la clase I y clase III esqueletal en hombres, se encontró una longitud menor en la vía aérea superior e inferior en la clase I. Las vías aéreas resultaron en menor tamaño en sujetos de clase II.

SUMMARY: To compare the airway permeability and the size of the maxillary sinuses in relation to the skeletal class. 90 lateral skull radiographs were divided into 3 groups, comparing the 3 skeletal classes, which were determined with Steiner's ANB measurement, and these were once in two subgroups that were men and women, in any McNamara analysis was used for the analysis of airways and for the maxillary sinus area measurements were made an antero-posterior and cephalic-caudal. When comparing males with females, statistical significance was identified in the upper class II route (p=≤0,017), lower class III airway (p=≤0.006). At least skeletal classes in men, differences were identified in the upper airway in classes I vs III (p=≤0.05), lower in class I vs III (p=≤0.001) and II vs III (p=≤0.044). With respect to women, significance was identified in the upper airway when comparing class I vs II (p=≤0.043), lower airway in class II vs. III (p=≤0.05), maxillary sinus length to class I vs II (p=≤0.017). Between skeletal class I and class II, maxillary sinus size was shorter in length in skeletal class II women. Between class I and skeletal class III in men, a lower length was found in the upper and lower airways in class I. The airways were found to be smaller in class II subjects.

Research progress of HDACs and associated inhibitors on regulation of acute lung injury / 中国药理学通报

Acute lung injury ( ALI) and its most extreme form a-cute respiratory distress syndrome ( ARDS) are lung diseases with high morbidity and mortality. There is no effective therapeutic intervention until now for its complicated pathophysiologi-cal processes and sophisticated regulatory mechanism. Histone deacetylases (HDACs) are a family of proteins with deacetylase activity. Studies have shown that HDACs are involved in the pathophysiological processes of ALI/ARDS, including inflammatory responses,endothelial permeability,oxidative stresses,alveolar fluid clearance and lung tissue repairment. Simultaneously, the use of HDACs inhibitors (HDACIs) can interfere with ALI/ ARDS progression. In this review we describe and summarize the pathophysiological processes and the underlying mechanisms in ALI/ARDS regulated by HDACs and HDACIs in detail, in order to provide the basis for the clinical application of HDACs-targe- ted agents and indicate directions for future study.

Role of CypD-mediated mPTP in melatonin improving cognitive impairment induced by repeated exposure to sevoflurane / 中国药理学通报

Aim To investigate the involvement of cy-clophilin D ( CypD ) -mediated mitochondrial permeability transition pore ( mPTP) in the neuroprotective effects of melatonin on cognitive impairment induced by repeated exposure to sevoflurane in newborn animals. Methods Mice were randomly assigned into control group, sevoflurane ( Sevo) group, and melatonin pre-treatment + sevoflurane ( Sevo + Mel) group. JC-1 kit was used to assess the mitochondrial membrane potential ( MMP) ; Western blot analysis was used to evaluate the protein expressions of CypD, postsynaptic density protein 95 ( PSD95 ), and Synapsin-1; and behavioral test were employed to measure cognitive function. Results The MMP level in the Sevo group was significantly reduced compared to the control group (P < 0. 01 ), the expression of CypD increased (P <0. 05), whereas the expression of PSD95 and Synapsin-1 decreased ( P < 0. 01) . Furthermore, the new object recognition index and spatial memory ability both exhibited a significant decline (P < 0. 01, P < 0. 05). However, when compared to the Sevo group, Sevo + Mel group could raise the MMP level (P <0. 01), increase the expression of synaptic proteins ( P < 0. 05 ), decrease the expression of CypD (P <0. 01) and elevate the new object recognition index and the spatial memory capacity ( P < 0. 01 ). Conclusions Melatonin could ameliorate cognitive impairment induced by repeated exposure to sevoflurane in newborn mice, and the underlying mechanism may be attributed to the inhibition of mPTP mediated by CypD and the promotion of synaptic protein synthesis.

Advances in the study of natural small molecules to protect the intestinal epithelial tight junction barrier in inflammatory bowel disease / 中国药理学通报

Inflammatory bowel disease (IBD), as an idiopathic inflammatory disease of the intestinal tract, consisting mainly of Crohns disease and ulcerative colitis, which can involve the rectum, colon and ileum, and whose pathogenesis is still not fully understood. The initiation of intestinal inflammation associated with IBD and its chronieity begins with increased intestinal permeability caused by intestinal epithelial barrier disruption. The anti-permeability of the intestinal epithelial barrier is maintained by tight junction in the apical region of the intestinal epithelial cells, and disruption of the tight junction structure is closely associated with intestinal epithelial barrier damage and the development of IBD. Therefore, it is significant to find drugs for the prevention and treatment of IBD using tight junctions as regulatory targets. In recent years, many small molecules of natural product origin have been reported to improve the effects of IBD. In particular, we review the compounds that have the function of repairing intestinal epithelial barrier and protecting tight junction structure, in order to provide research ideas for the design and development of new drugs for the prevention and treatment of IBD.

ADT-OH improves intestinal barrier function and remodels the gut microbiota in DSS-induced colitis / 医学前沿

Owing to the increasing incidence and prevalence of inflammatory bowel disease (IBD) worldwide, effective and safe treatments for IBD are urgently needed. Hydrogen sulfide (H2S) is an endogenous gasotransmitter and plays an important role in inflammation. To date, H2S-releasing agents are viewed as potential anti-inflammatory drugs. The slow-releasing H2S donor 5-(4-hydroxyphenyl)-3H-1,2-dithiole-3-thione (ADT-OH), known as a potent therapeutic with chemopreventive and cytoprotective properties, has received attention recently. Here, we reported its anti-inflammatory effects on dextran sodium sulfate (DSS)-induced acute (7 days) and chronic (30 days) colitis. We found that ADT-OH effectively reduced the DSS-colitis clinical score and reversed the inflammation-induced shortening of colon length. Moreover, ADT-OH reduced intestinal inflammation by suppressing the nuclear factor kappa-B pathway. In vivo and in vitro results showed that ADT-OH decreased intestinal permeability by increasing the expression of zonula occludens-1 and occludin and blocking increases in myosin II regulatory light chain phosphorylation and epithelial myosin light chain kinase protein expression levels. In addition, ADT-OH restored intestinal microbiota dysbiosis characterized by the significantly increased abundance of Muribaculaceae and Alistipes and markedly decreased abundance of Helicobacter, Mucispirillum, Parasutterella, and Desulfovibrio. Transplanting ADT-OH-modulated microbiota can alleviate DSS-induced colitis and negatively regulate the expression of local and systemic proinflammatory cytokines. Collectively, ADT-OH is safe without any short-term (5 days) or long-term (30 days) toxicological adverse effects and can be used as an alternative therapeutic agent for IBD treatment.

Effectiveness of three auxiliary irrigation methods for cleaning the internal walls of root canals of curved isolated teeth / 华西口腔医学杂志

OBJECTIVES@#This study aimed to compare the effectiveness of ultrasound and acoustic and laser cleaning of curved root canals.@*METHODS@#A total of 92 molars with independent root canals with a curvature of 20°-40° were prepared and standardized at 04 25# and stained with gentian violet solution for 72 h. Among them, 52 were randomly divi-ded into four groups for final rinsing (n=13): NI group, PUI group, EDDY group, and PIPS group. Ten samples in each group were cut horizontally along the long axis perpendicular to the root and divided into curved upper, curved, and apical segments. Images were taken with a stereomicroscope and Image J measurements were taken to calculate the depth of rinse penetration. The remaining three samples from each group were split along the long axis of the dentin, photographed by scanning electron microscope to record the dentin tubule exposure and staining layer, and scored for staining layer by double-blind method. SPSS 26.0 software was used to perform statistical analysis and select the best flushing method. An extra 40 samples were randomly divided into four groups for detection of flushing fluid penetration depth (n=10): 10, 20, 30, and 40 s.@*RESULTS@#In the upper part, the mean depth of infiltration was not significantly different between the experimental and control groups (P>0.05). The PIPS group had a significantly lower smear layer score than the control group and the EDDY group (P<0.01). In the curved segment, the mean depth of infiltration was significantly greater in the PUI group than in the control group (P<0.05); the tarnish layer score was lower in each experimental group than in the control group. At the top, the mean depth of infiltration was greater in the PUI and PIPS groups than in the control group (P<0.05), and the smear layer score was lower in the PIPS group than in the other groups (P<0.05). After the time was changed, the depth of infiltration of PUI increased only in the apical segment as the flushing time increased.@*CONCLUSIONS@#The PUI and PIPS methods facilitate the penetration of irrigation solution into the dentin canal in curved root canals, especially in the apical segment. The PIPS technique is effective in removing the smear layer in curved root canals.

Preliminary study on HUVEC permeability changes in FNAIT induced by CD36 antibody / 中国输血杂志

【Objective】 To explore the pathogenesis of fetal edema caused by CD36 antibody in fetal/neonatal alloimmune thrombocytopenia (FNAIT), and to provide reference for clinical prevention and treatment. 【Methods】 The established CD36 monoclonal antibody was incubated with human peripheral blood mononuclear cells (PBMC), and the concentrations of cytokines (TNF-α and IL-1β) in the supernatant of cell culture were detected by ELISA. The permeability of endothelial cells were investigated by detecting the fluorescence intensity of FITC-albumin by incubating cytokine-rich cell supernatant with human umbilical vein endothelial cells (HUVEC). 【Results】 Flow cytometry showed that CD36 monoclonal antibody could bind to human monocytes. Compared with isotype IgG control, increased cytokine TNF-α (pg/mL) (407.73±20.40 vs 29.38 ±4.72, P<0.05) and IL-1β (pg/mL) (247.14±83.59 vs 53.68±26.96, P<0.05) were detected in the supernatant of cell culture after incubation of CD36 monoclonal antibody with human PBMC. Detection of fluorescence intensity of FITC-albumin in transwell cultured HUVEC showed that cytokine-rich cell supernatant derived from CD36 monoclonal antibody incubated with human PBMC can increase the permeability of endothelial cells significantly (CD36 antibody vs isotype IgG, MFI value: 492±16 vs 320±11, P<0.05). 【Conclusion】 The effect of CD36 monoclonal antibody on PBMC can increase HUVEC permeability, which may be one of the pathogenesis of fetal edema with FNAIT.

Tritium permeation resistance of Al-Al₂O₃ coatings prepared by thermal spraying / 中国辐射卫生

@#<b>Objective</b> To make the preparation method for coatings more convenient in the field where the requirements for tritium permeation resistance are not high, this paper proposes a method for preparing Al-Al₂O₃ tritium permeation barriers by thermal spraying technology and conducts a performance analysis. <b>Methods</b> The tritium permeation resistance and adhesion of Al-Al₂O₃ coatings prepared by thermal spraying were verified by experiments. <b>Results</b> The tritium permeability was reduced by one order of magnitude after a 0.2-mm Al-Al₂O₃ coating was sprayed on the stainless steel surface, and the tritium permeation resistance had no significant improvement with the increase in coating thickness; the adhesion of the coating was determined in the range of 5-10 N by scratch tests. <b>Conclusion</b> In this paper, a simple preparation method for tritium permeation barrier is proposed, and the tritium permeation resistance performance of Al-Al₂O₃ coatings prepared by thermal spraying technology is determined, which provides a reference for the selection of tritium permeation barrier in the field of tritium-containing solid waste storage.

Protective effect and mechanism of mesenchymal stem cell-derived extracellular vesicle on radiation-induced liver injury / 器官移植

Objective To evaluate the protective effect and the underlying mechanism of mesenchymal stem cell-derived extracellular vesicle (MSC-EV) on radiation-induced liver injury and liver cell line injury in mouse models. Methods C57BL/6 mice were randomly divided into the blank group, model group and MSC-EV treatment group (treatment group), with 9 mice in each group. AML12 cells were randomly divided into the control group, irradiation group and MSC-EV intervention group (intervention group). Animal and cell models with radiation-induced injury were established by one-time 15 Gy and 6 Gy X-ray irradiation, respectively. At 48 h after irradiation, liver tissues and serum samples of mice were collected and prepared for subsequent experiments. At 15 h post-irradiation, cell experiment was carried out. Serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and content of malondialdehyde (MDA) in liver tissues and cells were measured. The relative expression levels of interleukin (IL)-1β, IL-6, transforming growth factor (TGF)-β and CXC chemokine ligand (CXCL)10 messenger RNA (mRNA) were detected by real-time fluorescent quantitative polymerase chain reaction (RT-qPCR). Liver tissues were prepared for hematoxylin-eosin (HE) staining to calculate liver pathological injury score. The apoptosis of liver tissues and cells was assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) and propidiumiodide (PI) staining, respectively. The expression levels of glutathione peroxidase 4 (GPX4) and ferroptosis suppressor protein 1 (FSP1) proteins were detected by Western blot. The production level of reactive oxygen species (ROS) was detected by dihydroethidine (DHE) staining. The fluorescence intensity of mitochondrial permeability transition pore (mPTP) was determined. Results Compared with the blank group, serum levels of AST and ALT were up-regulated, and the relative expression levels of IL-1β, TGF-β and CXCL10 mRNA in the mouse liver tissues were up-regulated, and MDA content was increased, liver injury score was elevated, cell apoptosis rate was increased, intracellular ROS level was elevated, and the relative expression levels of GPX4 and FSP1 proteins in the mouse liver tissues were down-regulated in the model group, and the differences were statistically significant (all P<0.05). Compared with the model group, serum levels of AST and ALT were decreased, and the relative expression levels of IL-1β, TGF-β and CXCL10 mRNA in the liver tissues of mice were down-regulated, MDA content was declined, liver injury score was declined, cell apoptosis rate was decreased, intracellular ROS level was decreased, and the relative expression levels of GPX4 and FSP1 proteins in the liver tissues of mice were up-regulated in the treatment group, and the differences were statistically significant (all P<0.05). Compared with the control group, cell apoptosis rate was increased, intracellular ROS level was elevated, the fluorescence intensity of mPTP was weakened, the relative expression levels of IL-1β, TGF-β and IL-6 mRNA were up-regulated, MDA content was increased, and the relative expression levels of GPX4 and FSP1 proteins were down-regulated in the irradiation group, and the differences were statistically significant (all P<0.05). Compared with the irradiation group, cell apoptosis rate was declined, intracellular ROS level was decreased, the fluorescence intensity of mPTP was strengthened, the relative expression levels of IL-1β, TGF-β and IL-6 mRNA were down-regulated, MDA content was decreased and the relative expression levels of GPX4 and FSP1 proteins were up-regulated in the intervention group, and the differences were statistically significant (all P<0.05). Conclusions MSC-EV may effectively alleviate radiation-induced liver injury by reducing ferroptosis of liver cells, enhancing antioxidant level and decreasing the production of lipid peroxide, thereby effectively alleviating radiation-induced liver injury.

Research Progress on Capillary Leak Syndrome Associated with Hematopoietic Stem Cell Transplantation--Review / 中国实验血液学杂志

Capillary leak syndrome (CLS) is a clinical syndrome characterized by impairment of vascular endothelial barrier function, increased vascular permeability, and reversible systemic edema. It is one of the early fatal complications after hematopoietic stem cell transplantation. So far, the exact pathogenesis of CLS has not been elucidated, and the diagnostic criteria and treatment methods have not been unified. At present, it is believed that the fundamental cause of CLS is hypercytokinemia, and the core factor is high permeability of vascular endothelial cells. According to the clinical manifestations, the natural course of CLS can be divided into prodrome, leakage and recovery stages. As far as treatment is concerned, symptomatic and supportive treatment is dominant according to different characteristics of each stage. In this review, the pathogenesis, clinical manifestations, diagnosis and treatment of hematopoietic stem cell transplant-associated CLS were briefly summarized.

Resampling combined with stacking learning for prediction of blood-brain barrier permeability of compounds / 生物医学工程学杂志

It is a significant challenge to improve the blood-brain barrier (BBB) permeability of central nervous system (CNS) drugs in their development. Compared with traditional pharmacokinetic property tests, machine learning techniques have been proven to effectively and cost-effectively predict the BBB permeability of CNS drugs. In this study, we introduce a high-performance BBB permeability prediction model named balanced-stacking-learning based BBB permeability predictor(BSL-B3PP). Firstly, we screen out the feature set that has a strong influence on BBB permeability from the perspective of medicinal chemistry background and machine learning respectively, and summarize the BBB positive(BBB+) quantification intervals. Then, a combination of resampling algorithms and stacking learning(SL) algorithm is used for predicting the BBB permeability of CNS drugs. The BSL-B3PP model is constructed based on a large-scale BBB database (B3DB). Experimental validation shows an area under curve (AUC) of 97.8% and a Matthews correlation coefficient (MCC) of 85.5%. This model demonstrates promising BBB permeability prediction capability, particularly for drugs that cannot penetrate the BBB, which helps reduce CNS drug development costs and accelerate the CNS drug development process.

Muscone inhibits opening of mPTP to alleviate OGD/R-induced injury of HT22 cells / 中国中药杂志

This study aims to investigate the mechanism of muscone in inhibiting the opening of mitochondrial permeability transition pore(mPTP) to alleviate the oxygen and glucose deprivation/reoxygenation(OGD/R)-induced injury of mouse hippocampal neurons(HT22). An in vitro model of HT22 cells injured by OGD/R was established. CCK-8 assay was employed to examine the viability of HT22 cells, fluorescence microscopy to measure the mitochondrial membrane potential, the content of reactive oxygen species(ROS), and the opening of mPTP in HT22 cells. Enzyme-linked immunosorbent assay was employed to determine the level of ATP and the content of cytochrome C(Cyt C) in mitochondria of HT22 cells. Flow cytometry was employed to determine the Ca~(2+) content and apoptosis of HT22 cells. The expression of Bcl-2(B-cell lymphoma-2) and Bcl-2-associated X protein(Bax) was measured by Western blot. Molecular docking and Western blot were employed to examine the binding between muscone and methyl ethyl ketone(MEK) after pronase hydrolysis of HT22 cell proteins. After the HT22 cells were treated with U0126, an inhibitor of MEK, the expression levels of MEK, p-ERK, and CypD were measured by Western blot. The results showed that compared with the OGD/R model group, muscone significantly increased the viability, mitochondrial ATP activity, and mitochondrial membrane potential, lowered the levels of ROS, Cyt C, and Ca~(2+), and reduced mPTP opening to inhibit the apoptosis of HT22 cells. In addition, muscone up-regulated the expression of MEK, p-ERK, and down-regulated that of CypD. Molecular docking showed strong binding activity between muscone and MEK. In conclusion, muscone inhibits the opening of mPTP to inhibit apoptosis, thus exerting a protective effect on OGD/R-injured HT22 cells, which is associated with the activation of MEK/ERK/CypD signaling pathway.

Improvement of solubility of epimedium flavonoid secondary glycoside components by traditional Chinese medicine polysaccharides and its mechanism / 中国中药杂志

The poor solubility of insoluble components of traditional Chinese medicine(TCM) is an important factor restricting the development of its preparations. Natural polysaccharides of TCM can be used as functional components to increase the solubility of insoluble components. Epimedium flavonoid secondary glycoside components(EFSGC) have been shown to have positive effects on the prevention and treatment of osteoporosis, but they exhibit poor solubility. Therefore, the strategy of solubilizing EFSGC with TCM polysaccharides was adopted, and its effect on the permeability and stability of EFSGC was evaluated in this study. Based on the equilibrium solubility experiment of EFSGC, it was found that Panax notoginseng crude polysaccharide(PNCP) had the best solubilization effect on EFSGC among the ten kinds of TCM polysaccharides, which increased the solubility of EFSGC from 0.8 mg·mL~(-1) to 13.3 mg·mL~(-1). It should be noted that after the solubilization of EFSGC by preparation technology, the effects on permeability and stability should be considered. Therefore, this study also investigated these two properties. The results showed that PNCP increased the effective transmittance of EFSGC from 50.5% to 71.1%, which could increase the permeability of EFSGC significantly. At the same time, it could improve the stability of EFSGC in the simulated gastric juice environment. In order to explain the solubilization mechanism of PNCP on EGSGC, critical micelle concentration, particle size, potential, differential scanning calorimetry, and infrared spectroscopy were analyzed. It was preliminarily inferred that the mechanism was as follows: PNCP and EFSGC could self-assemble into aggregates for solubilization by intermolecular hydrogen bonding interaction in water. In summary, PNCP can not only improve the solubility of EFSGC but also improve its permeability and stability. This study lays the foundation for the application of TCM polysaccharides as a functional component to solubilize insoluble components.

Changes of intestinal wall barrier function and its correlation with susceptibility to infection in patients with cirrhotic portal hypertension / 中华肝脏病杂志

Objective: To investigate the changes of intestinal wall barrier function and its correlation with infection occurrence in patients with cirrhotic portal hypertension. Methods: 263 patients with cirrhotic portal hypertension were split into: the clinically evident portal hypertension (CEPH) combined with infection group (n = 74); CEPH group (n = 104); and Non-CEPH group (n = 85). Among them, 20 CEPH patients and 12 non-CEPH patients in non-infection status were subjected to sigmoidoscopy. Immunohistochemical staining was used to detect the expression of trigger receptor-1 (TREM-1), CD68, CD14, the inducible nitric oxide synthase molecule, and Escherichia coli (E.coli) in the medullary cells of the colon mucosa. An enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of soluble myeloid cell trigger receptor-1 (sTREM-1), soluble leukocyte differentiation antigen-14 subtype (sCD14-ST) and intestinal wall permeability index enteric fatty acid binding protein (I-FABP). Fisher's exact probability method, one-way ANOVA, Kruskal-Wallis-H test, Bonferroni method, and Spearman correlation analysis were used for statistical analysis. Results: The serum sTREM-1 and I-FABP levels were higher in CEPH patients than those of non-CEPH patients in the non-infectious state (P < 0.05), but the difference in blood sCD14-ST levels was not statistically significant (P > 0.05). Serum levels of sTREM-1, sCD14-ST, and I-FABP in infected patients were higher than those in patients without a concurrent infection (P < 0.05). Serum sCD14-ST levels were positively correlated with serum sTREM-1, C-reactive protein (CRP), and procalcitonin (PCT), and sTREM-1 levels were also positively correlated with CRP and PCT (r > 0.5, P < 0.001). The rates of CD68, inducible nitric oxide synthase, CD14-positive cells, and E.coli-positive glands were higher in the intestinal mucosa of the CEPH group than those of the control group (P < 0.05). Spearman's correlation analysis showed that the rate of E.coli-positive glands in CEPH patients was positively correlated with the expression of molecular markers CD68 and CD14 in the lamina propria macrophages. Conclusion: Patients with cirrhotic portal hypertension have increased intestinal permeability and inflammatory cells, accompanied by bacterial translocation. Serum sCD14-ST and sTREM-1 can be used as indicators to predict and evaluate the occurrence of infection in patients with cirrhotic portal hypertension.

Clinicopathological features analysis of focal segmental glomerulosclerosis after kidney transplantation / 器官移植

Objective To investigate the clinicopathological features of recurrent and de novo focal segmental glomerulosclerosis (FSGS) after kidney transplantation. Methods Thirty-four recipients pathologically diagnosed with FSGS by renal allograft biopsy were enrolled in this clinical trial. According to the detection of primary diseases of renal allografts and circulating permeability factors, 34 recipients were divided into the recurrent FSGS group (n=12) and de novo FSGS group (n=22). The differences of clinical indexes and the degree of pathological injury of renal allografts were compared between two groups. Results There was no significant difference in the mesangial hyperplasia score, glomerulosclerosis rate, renal tubular atrophy score, interstitial fibrosis score and podocyte proliferation rate between two groups (all P > 0.05). In the recurrent FSGS group, segmental glomerulosclerosis rate of the recipients was 0.10 (0.08, 0.27), lower than 0.19 (0.13, 0.33) in the de novo FSGS group (P < 0.05). No significant difference was found in the incidence of antibody-mediated rejection, drug-induced renal tubular injury and BK virus infection between two groups (all P > 0.05). The incidence of T cell-mediated rejection in the recurrent FSGS group was 17%, lower than 55% in the de novo FSGS group (P < 0.05). Immunohistochemical staining showed that the infiltrating inflammatory cells in the renal allografts were mainly T lymphocytes. The positive rates of C4d deposition in peripheral capillaries between the recurrent and de novo FSGS groups were 33% (4/12) and 32% (7/22), with no significant difference (P > 0.05). Immunofluorescence results revealed IgM deposition in the segmental glomerulosclerosis area of renal allografts in most cases. Electron microscopy showed extensive fusion or segmental distribution of podocytes in the glomerulus of renal allografts. Conclusions The degree of renal functional injury and the incidence of T cell-mediated rejection in the recurrent FSGS group are lower than those in the de novo FSGS group. Comprehensive analysis of preoperative and postoperative clinical manifestations, laboratory testing and pathological examination of kidney transplant recipients contribute to early diagnosis and treatment of recurrent and de novo FSGS.

La vitamina C, implicaciones terapéuticas en el paciente con quemaduras graves / Vitamin C, therapeutic implications in the patient with serious burns / Vitamina C, implicações terapêuticas no paciente com queimaduras graves

Resumen: La atención a pacientes con quemaduras extensas es compleja, la quemadura condiciona efectos en el sitio de la lesión y a nivel sistémico. A nivel de la microcirculación se presenta respuesta de mediadores químicos inflamatorios y excesiva producción de especies reactivas de oxígeno y nitrógeno, además condiciona disminución de la capacidad antioxidante de vitamina C, por lo que se altera el balance fisiológico de óxido-reducción, dando paso al estado de estrés oxidativo, esto trae como consecuencia un incremento en la inflamación, disfunción endotelial e incremento de la permeabilidad capilar. Uno de los objetivos de la reanimación del paciente quemado es restaurar el volumen intravascular generado por el estado de choque, en el cual se implementan estrategias como el uso de cristaloides, coloides, plasma, terapias dialíticas, uso limitado de opioides y la administración de vitamina C. El objetivo de este trabajo es dar a conocer a la comunidad médica las características físicas y químicas, los mecanismos moleculares de la vitamina C en los que se encuentra implicada en condiciones de quemaduras graves, con la finalidad de la implementación durante la fase de reanimación del quemado.

Abstract: The care of patients with extensive burns is complex, the burn conditions effects at the site of the injury and at the systemic level. At the microcirculation level, there is a response of inflammatory chemical mediators and excessive production of reactive oxygen and nitrogen species, which also causes a decrease in the antioxidant capacity of vitamin C, which is why the physiological balance of oxide-reduction is altered, giving way to the state of oxidative stress, this results in an increase in inflammation, endothelial dysfunction and an increase in capillary permeability. One of the objectives of the resuscitation of the burned patient is to restore the intravascular volume generated by the state of shock, in which strategies such as the use of crystalloids, colloids, plasma, dialysis therapies, limited use of opioids and the administration of vitamins are implemented C. The objective of this work is to make known to the medical community, the physical and chemical characteristics, the molecular mechanisms of vitamin C in which it is involved in severe burn conditions, with the purpose of implementation during the resuscitation phase of burn.

Resumo: O atendimento a pacientes com queimaduras extensas é complexo, a queimadura condiciona efeitos no local da lesão e em nível sistêmico. Ao nível da microcirculação, há uma resposta de mediadores químicos inflamatórios e produção excessiva de espécies reativas de oxigénio e nitrogênio, condiciona também uma diminuição da capacidade antioxidante da vitamina C, que altera o equilíbrio fisiológico de oxidação-redução, dando lugar a o estado de estresse oxidativo, isso resulta em aumento da inflamação, disfunção endotelial e aumento da permeabilidade capilar. Um dos objetivos da ressuscitação do paciente queimado é restaurar o volume intravascular gerado pelo estado de choque, no qual se implementam estratégias como o uso de cristalóides, colóides, plasma, terapias dialíticas, uso limitado de opióides e administração de vitamina C. O objetivo deste trabalho é dar a conhecer à comunidade médica as características físicas e químicas, os mecanismos moleculares da vitamina C em que está envolvida em condições de queimaduras graves, com vista à sua aplicação durante a fase de reanimação do paciente queimado.