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Abdominal paracentesis drainage ameliorates severe acute pancreatitis in rats by regulating the polarization of peritoneal macrophages

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World Journal of Gastroenterology 2018年第45期24卷 5131-5143页

作者： Ruo-Hong Liu Yi Wen Hong-Yu Sun Chun-Yu Liu Yu-Fan Zhang Yi Yang Qi-Lin Huang jia-jia tang Can-Chen Huang Li-Jun tang PLA Center of General Surgery and Pancreatic Injury and Repair Key Laboratory of Sichuan Province Chengdu Military General HospitalChengdu 610083Sichuan ProvinceChina Third Military Medical University(Army Medical University) Chongqing 400037China jiaotong Hospital Affiliated with the Sichuan Provincial People’s Hospital Chengdu 611730Sichuan ProvinceChina Department of Ultrasound Chinese Academy of Medical Sciences and Peking Union Medical College HospitalBeijing 100032China

AIM To investigate the role of peritoneal macrophage(PM) polarization in the therapeutic effect of abdominal paracentesis drainage(APD) on severe acute pancreatitis(SAP).METHODS SAP was induced by 5% Na-taurocholate retrograde injection in Sprague-Dawley rats. APD was performed by inserting a drainage tube with a vacuum ball into the lower right abdomen of the rats immediately after the induction of SAP. To verify the effect of APD on macrophages, PMs were isolated and cultured in an environment, with the peritoneal inflammatory environment simulated by the addition of peritoneal lavage in complete RPMI 1640 medium. Hematoxylin and eosin staining was performed. The levels of pancreatitis biomarkers amylase and lipase as well as the levels of inflammatory mediators in the blood and peritoneal lavage were determined. The polarization phenotypes of the PMs were identified by detecting the marker expression of M1/M2 macrophages via flow cytometry, qPCR and immunohistochemical staining. The protein expression in macrophages that had infiltrated the pancreas was determined by Western blot.RESULTS APD treatment significantly reduced the histopathological scores and levels of amylase, lipase, tumor necrosis factor-α and interleukin(IL)-1β, indicating that APD ameliorates the severity of SAP. Importantly, we found that APD treatment polarized PMs towards the M2 phenotype, as evidenced by the reduced number of M1 macrophages and the reduced levels of proinflammatory mediators, such as IL-1β and L-selectin, as well as the increased number of M2 macrophages and increased levels of anti-inflammatory mediators, such as IL-4 and IL-10. Furthermore, in an in vitro study wherein peritoneal lavage from the APD group was added to the cultured PMs to simulate the peritoneal inflammatory environment, PMs also exhibited a dominant M2 phenotype, resulting in a significantly lower level of inflammation. Finally, APD treatment increased the proportion of M2 macrophages and upregulated the expression of the anti-inflammatory protein Arg-1

关键词： Abdominal paracentesis drainage Peritoneal macrophages Polarization Severe acute pancreatitis

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Targeted therapies for lupus nephritis:Current perspectives and future directions

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Chinese Medical Journal 2024年第1期137卷 34-43页

作者： Xiuzhi jia Yuewen Lu Xunhua Zheng Ruihan tang Wei Chen Department of Nephrology The First Affiliated HospitalSun Yat-Sen UniversityGuangzhouGuangdong 510080China NHC Key Laboratory of Clinical Nephrology(Sun Yat-Sen University) and Guangdong Provincial Key Laboratory of NephrologyGuangzhouGuangdong 510080China

Lupus nephritis(LN),a severe manifestation of systemic lupus erythematosus,poses a substantial risk of progression to end-stage renal disease,with increased mortality.Conventional therapy for LN relies on broad-spectrum immunosuppressants such as glucocorticoids,mycophenolate mofetil,and calcineurin inhibitors.Although therapeutic regimens have evolved over the years,they have inherent limitations,including non-specific targeting,substantial adverse effects,high relapse rates,and prolonged maintenance and remission courses.These drawbacks underscore the need for targeted therapeutic strategies for LN.Recent advancements in our understanding of LN pathogenesis have led to the identification of novel therapeutic targets and the emergence of biological agents and small-molecule inhibitors with improved specificity and reduced toxicity.This review provides an overview of the current evidence on targeted therapies for LN,elucidates the biological mechanisms of responses and failure,highlights the challenges ahead,and outlines strategies for subsequent clinical trials and integrated immunomodulatory approaches.

关键词： Lupus nephritis Molecular targeted therapies Adaptive immunity Immunity,Innate Cytokines

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Curcumin cytotoxicity is enhanced by PTEN disruption in colorectal cancer cells

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World Journal of Gastroenterology 2013年第40期19卷 6814-6824页

作者： Lin Chen Wen-Feng Li Hong-Xiao Wang Hai-Na Zhao jia-jia tang Chang-Jie Wu Li-Ting Lu Wan-Qin Liao Xin-Cheng Lu Institute of Genomic Medicine Wenzhou Medical University Department of Oncology First Affiliated Hospital of Wenzhou Medical University

AIM:To investigate the effects of phosphatase and tensin homolog deleted on chromosome 10(PTEN) deficiency on the cytotoxicity of chemotherapeutic agents toward colorectal cancer cells.METHODS:PTEN-deficient colorectal cancer(CRC) cells were generated by human somatic cell gene targeting using the adeno-associated virus system. The cytotoxic effects of compounds including curcumin,5-fluorouracil(5-FU),dihydroartemisinin(DHA),irinotecan(CPT-11)and oxaliplatin(OXA) on cancer cells were determined using the MTT assay. Enhanced cytotoxicity of curcumin in PTEN-deficient CRC cells was observed,and this was confirmed using clonogenic assays. Apoptosis and cell cycle progression were analyzed by flow cytometry.Levels of apoptosis and cell cycle-related proteins were examined by Western blotting.RESULTS:We developed an isogenic set of CRC cell lines that differed only in their PTEN status. Using this set of cell lines,we found that disruption of the PTEN gene had no effect on the sensitivity of CRC cells to5-FU,CPT-11,DHA,or OXA,whereas PTEN disruption increased the sensitivity of CRC cells to curcumin. Loss of PTEN did not alter the curcumin-induced apoptosis in CRC cells. However,PTEN deficiency led to an altered pattern of curcumin-mediated cell cycle arrest.In HCT116 PTEN+/+cells,curcumin caused a G2/M phase arrest,whereas it caused a G0/G1 phase arrest in HCT116 PTEN-/-cells. Levels of cell cycle-related proteins were consistent with these respective patterns of cell cycle arrest.CONCLUSION:Curcumin shows enhanced cytotoxicity toward PTEN-deficient cancer cells,suggesting that it might be a potential chemotherapeutic agent for cancers harboring PTEN mutations.

关键词： Phosphatase and tensin homolog deleted on chromosome 10 Curcumin Chemotherapeutic agents Cell cycle AKT signaling

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Optimization of the co-closing law of guide vanes and blades for bulb turbines based on CFD

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Journal of Hydrodynamics 2024年第2期36卷 363-377页

作者： Hui Liu Yun-fa Lin Yong-guang Cheng Song Xue Mao-jia tang jian Zhang jia-yi Fan State Key Laboratory of Water Resources Engineering and Management Wuhan UniversityWuhan430072China Dongfang Electric Machinery Co. Ltd.Deyang618000China

The load rejection transient process of bulb turbine units is critical to safety of hydropower stations,and determining appropriate closing laws of guide vanes(GVs)and runner blades(RBs)for this process is of significance.In this study,we proposed a procedure to optimize the co-closing law of GVs and RBs by using computational fluid dynamics(CFD),combined with the design of experiment(DOE)method,approximation model,and genetic optimization algorithm.The sensitivity of closing law parameters on the histories of head,speed,and thrust was analyzed,and a two-stage GVs’closing law associating with a linear RBs’closing law was proposed.The results show that GVs dominate the transient characteristics by controlling the change of discharge.Speeding GVs’first-stage closing speed while shortening first-stage closing time can not only significantly reduce the maximum rotational speed but also suppress the water hammer pressure;slowing GVs’second-stage closing speed is conducive to controlling the maximum reverse axial force.RBs directly affect the runner force.Slowing RBs’closing speed can further reduce the rotational speed and the maximum reverse axial force.The safety margin of each control parameter,flow patterns,and pressure pulsations of a practical hydropower station were all improved after optimization,demonstrating the effectiveness of this method.

关键词： Bulb turbine load rejection transient process double regulation closing law optimization computational fluid dynamics(CFD)

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Effects of thawing-induced softening on fracture behaviors of frozen rock

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Journal of Rock Mechanics and Geotechnical Engineering 2024年第3期16卷 979-989页

作者： Ting Wang Hailiang jia Qiang Sun Xianjun Tan Liyun tang College of Geology and Environment Xi’an University of Science and TechnologyXi’an710054China College of Architecture and Civil Engineering Xi’an University of Science and TechnologyXi’an710054China State Key Laboratory of Geomechanics and Geotechnical Engineering Institute of Rock and Soil MechanicsChinese Academy of SciencesWuhan430064China

Due to the presence of ice and unfrozen water in pores of frozen rock,the rock fracture behaviors are susceptible to temperature.In this study,the potential thawing-induced softening effects on the fracture behaviors of frozen rock is evaluated by testing the tension fracture toughness(KIC)of frozen rock at different temperatures(i.e.-20℃,-15℃,-12℃,-10℃,-8℃,-6℃,-4℃,-2℃,and 0℃).Acoustic emission(AE)and digital image correlation(DIC)methods are utilized to analyze the microcrack propagation during fracturing.The melting of pore ice is measured using nuclear magnetic resonance(NMR)method.The results indicate that:(1)The KIC of frozen rock decreases moderately between-20℃ and-4℃,and rapidly between-4℃ and 0℃.(2)At-20℃ to-4℃,the fracturing process,deduced from the DIC results at the notch tip,exhibits three stages:elastic deformation,microcrack propagation and microcrack coalescence.However,at-4℃e0℃,only the latter two stages are observed.(3)At-4℃e0℃,the AE activities during fracturing are less than that at-20℃ to-4℃,while more small events are reported.(4)The NMR results demonstrate a reverse variation trend in pore ice content with increasing temperature,that is,a moderate decrease is followed by a sharp decrease and-4℃ is exactly the critical temperature.Next,we interpret the thawing-induced softening effect by linking the evolution in microscopic structure of frozen rock with its macroscopic fracture behaviors as follow:from-20℃ to-4℃,the thickening of the unfrozen water film diminishes the cementation strength between ice and rock skeleton,leading to the decrease in fracture parameters.From-4℃ to 0℃,the cementation effect of ice almost vanishes,and the filling effect of pore ice is reduced significantly,which facilitates microcrack propagation and thus the easier fracture of frozen rocks.

关键词： Frozen sandstone Different thawing temperature Fracture toughness Microcrack propagation process Unfrozen water content

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Cross-linkedα-amylase aggregates on Fe3O4 magnetic nanoparticles modified with polydopamine/polyethyleneimine for efficient hydrolysis of starch

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Particuology 2024年第7期90卷 98-105页

作者： jiandong Cui Xiuming tang Qingqing Ma Yuyan Chang Qunli Zhang Shiru jia State Key Laboratory of Food Nutrition and Safety Laboratory of Industrial Fermentation MicrobiologyMinistry of EducationTianjin University of Science and TechnologyTianjin 300457China Key Laboratory of Biomass Chemical Engineering of Ministry of Education Zhejiang UniversityHangzhou 310027China

In this workα-amylase was immobilized on magnetic Fe3O4 nanoparticles with polyethylenimine(PEI)/polydopamine(PDA)coating or 3-aminopropyl triethoxysilane(APTES)for the first time via adsorption–precipitation–cross-linking.Compared with the freeα-amylase,the resultant magnetic cross-linkedα-amylase aggregates(PEI/PDA-M-CLEAs and N-M-CLEAs)exhibited excellent thermal and storage stability as well as pH stability.After storage at 25°C for 60 days,freeα-amylase only retained 60%of its initial activity,while PEI/PDA-M-CLEAs and N-M-CLEAs retained 80%and 78%of their initial activities,respectively.Furthermore,N-M-CLEAs and PEI/PDA-M-CLEAs showed good reusability.After 6 repeated uses,PEI/PDA-M-CLEAs and N-M-CLEAs still maintained 65%and 62%of their initial activities,respectively.Especially,PEI/PDA-M-CLEAs and N-M-CLEAs exhibited higher starch hydrolysis efficiency than freeα-amylase.The maximum dextrose equivalent(DE)values of starch hydrolysis by PEI/PDA-M-CLEAs and N-M-CLEAs reached 29.24%and 28.79%within 90 min,respectively.However,the maximum DE values of starch hydrolysis by the freeα-amylase was only 27.89%even in 150 min.The magnetic cross-linkedα-amylase aggregates could be introduced as effective biocatalyst for industrial applications in production of maltose syrups.

关键词： α-amylase Magnetic nanoparticles Functional modification Magnetic cross-linked enzyme aggregates Hydrolysis of starch

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Chemical Composition, Pharmacological Effects and Clinical Applications of Cinobufacini

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Chinese Journal of Integrative Medicine 2024年第4期30卷 366-378页

作者： ZUO Qian XU Ding-qiao YUE Shi-jun FU Rui-jia tang Yu-ping Key Laboratory of Shaanxi Administration of Traditional Chinese Medicine for TCM Compatibility Shaanxi University of Chinese MedicineXi'an(712046)China

Chinese medicine cinobufacini is an extract from the dried skin of Bufo bufo gargarizans Cantor,with active ingredients of bufadienolides and indole alkaloids.With further research and clinical applications,it is found that cinobufacini alone or in combination with other therapeutic methods can play an anti-tumor role by controlling proliferation of tumor cells,promoting apoptosis,inhibiting formation of tumor neovascularization,reversing multidrug resistance,and regulating immune response;it also has the functions of relieving cancer pain and regulating immune function.In this paper,the chemical composition,pharmacological effects,clinical applications,and adverse reactions of cinobufacini are summarized.However,the extraction of monomer components of cinobufacini,the relationship between different mechanisms,and the causes of adverse reactions need to be further studied.Also,high-quality clinical studies should be conducted.

关键词： cinobufacini chemical composition Chinese medicine pharmacological effect clinical application adverse effect

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Global trends in diabetic eye disease research from 2012 to 2021

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Neural Regeneration Research 2024年第10期19卷 2310-2320页

作者： Yuan Yuan Shangli Ji Yali Song Zhaodi Che Lu Xiao Shibo tang jia Xiao Aier School of Ophthalmology Central South UniversityChangshaHunan ProvinceChina Changsha Aier Eye Hospital ChangshaHunan ProvinceChina Aier Eye Institute ChangshaHunan ProvinceChina Department of Metabolic and Bariatric Surgery The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdong ProvinceChina

Diabetic eye disease refers to a group of eye complications that occur in diabetic patients and include diabetic retinopathy, diabetic macular edema, diabetic cataracts, and diabetic glaucoma. However, the global epidemiology of these conditions has not been well characterized. In this study, we collected information on diabetic eye disease-related research grants from seven representative countries––the United States, China, Japan, the United Kingdom, Spain, Germany, and France––by searching for all global diabetic eye disease journal articles in the Web of Science and Pub Med databases, all global registered clinical trials in the Clinical Trials database, and new drugs approved by the United States, China, Japan, and EU agencies from 2012 to 2021. During this time period, diabetic retinopathy accounted for the vast majority(89.53%) of the 2288 government research grants that were funded to investigate diabetic eye disease, followed by diabetic macular edema(9.27%). The United States granted the most research funding for diabetic eye disease out of the seven countries assessed. The research objectives of grants focusing on diabetic retinopathy and diabetic macular edema differed by country. Additionally, the United States was dominant in terms of research output, publishing 17.53% of global papers about diabetic eye disease and receiving 22.58% of total citations. The United States and the United Kingdom led international collaborations in research into diabetic eye disease. Of the 415 clinical trials that we identified, diabetic macular edema was the major disease that was targeted for drug development(58.19%). Approximately half of the trials(49.13%) pertained to angiogenesis. However, few drugs were approved for ophthalmic(40 out of 1830;2.19%) and diabetic eye disease(3 out of 1830;0.02%) applications. Our findings show that basic and translational research related to diabetic eye disease in the past decade has not been highly active, and has yielded few new treatment methods and newly approved drugs.

关键词： clinical trials diabetic cataracts diabetic eye disease diabetic glaucoma diabetic macular edema diabetic retinopathy drug development global research publication research grant

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Deep eutectic solvent-driven self-assembly of metal mercaptide complexes with enzyme-mimicking activities for detection of uric acid through one-step cascade catalytic reaction

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Green Chemical Engineering 2024年第1期5卷 75-84页

作者： Jean Claude Munyemana jia Chen Xin Li Yangxia Han Hao tang Hongdeng Qiu CAS Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province Lanzhou Institute of Chemical PhysicsChinese Academy of SciencesLanzhou730000China University of Chinese Academy of Sciences Chinese Academy of SciencesBeijing100039China Department of Pharmacy Gansu Provincial HospitalLanzhou730000China

This work presents a generic strategy to create a series of metal mercaptides complexes via coordination selfassembly between transition metals(Mn,Cu,Co,Fe,and Ni)and cysteine(Cys)by forming the sulfur-metal bridges.This strategy involves dissolving metal chlorides and Cys into deep eutectic solvents(DES),followed by the precipitation of metal mercaptides complexes(such as Cys-Mn)by adding water as an antisolvent,where DES serves as the solvent,shape directing,and capping agent,thereby preventing the formation of other metal impurities.Interestingly,the prepared complexes possess both laccase and peroxidase-like properties,allowing the design of a technique for the detection of L-3,4-dihydroxyphenylalanine(L-DOPA)and uric acid,respectively.The prepared Cys-Mn can linearly oxidize L-DOPA with its concentrations from 0.1 to 130μM and the detection limit was calculated to be 75.5 n M.Additionally,the Cys-Mn can mimic the activity of peroxidase towards oxidization of o-phenylenediamine at neutral p H,allowing single-step and one-pot cascade reactions for visual and fluorometric measurements of uric acid(UA)that could work in the range of 0.2-500μM UA with a detection limit of 0.06μM and 0.054μМ,respectively.The assay was successful in detecting UA in serum and urine samples with relative standard deviation(RSD)ranging from 7.3%to 10.2%and 3.0%-8.5%respectively,suggesting that it may prove useful in medical diagnostic testing.

关键词： Metal-mercaptides Deep eutectic solvents Self-assembly Peroxidase-mimic catalyst Uric acid detection

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Pathogen-induced methylglyoxal negatively regulates rice bacterial blight resistance by inhibiting OsCDR1 protease activity

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Molecular Plant 2024年第2期17卷 325-341页

作者： Zheng-Wei Fu jian-Hui Li Xiang Gao Shi-jia Wang Ting-Ting Yuan Ying-tang Lu State Key Laboratory of Hybrid Rice College of Life SciencesRenmin Hospital of Wuhan UniversityWuhan UniversityWuhan 430072China Key Laboratory of Biology and Genetic Improvement of OilCrops Ministry of Agriculture and Rural AffairsOilCrops Research Institute of the Chinese Academy of Agricultural SciencesWuhan 430062China

Xanthomonas oryzae pv.oryzae(Xoo)causes bacterial blight(BB),a globally devastating disease of rice(Oryza sativa)that is responsible for significant crop loss.Sugars and sugar metabolites are important for pathogen infection,providing energy and regulating events associated with defense responses;howev-er,the mechanisms by which they regulate such events in BB are unclear.As an inevitable sugar metabolite,methylglyoxal(MG)is involved in plant growth and responses to various abiotic stresses,but the underlying mechanisms remain enigmatic.Whether and how MG functions in plant biotic stress responses is almost completely unknown.Here,we report that the Xoo strain PXO99 induces OsWRKY62.1 to repress transcrip-tion of OsGLY Il genes by directly binding to their promoters,resulting in overaccumulation of MG.MG negatively regulates rice resistance against Pxo99:osglyll2 mutants with higher MG levels are more sus-ceptible to the pathogen,whereas OsGLYIl2-overexpressing plants with lower MG content show greater resistance than the wild type.Overexpression of OsGLYll2 to prevent excessive MG accumulation confers broad-spectrum resistance against the biotrophic bacterial pathogens Xoo and Xanthomonas oryzae pv.oryzicola and the necrotrophic fungal pathogen Rhizoctonia solani,which causes rice sheath blight.Further evidence shows that MG reduces rice resistance against PXO99 through CONSTITUTIVE DISEASE RESISTANCE 1(OsCDR1).MGmodifies the Arg97 residue of OsCDR1to inhibit its aspartic protease activ-ity,which is essential for OsCDR1-enhanced immunity.Taken together,these findings illustrate how Xoo promotes infection by hijacking a sugar metabolite in the host plant.

关键词： Oryza sativa bacterial blight OsWRKY62.1 methylglyoxal OsCDR1

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