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Calcium signaling of pancreatic acinar cells in the pathogenesis of pancreatitis

World Journal of Gastroenterology 2014年第43期20卷 16146-16152页

作者： Jun Li Rui Zhou Jian Zhang Zong-Fang Li national local joint engineering research center of biodiagnostics and biotherapy the Second Affiliated Hospital of Xi’an Jiaotong University College of Medicine Department of General Surgery National Local Joint Engineering Research Center of Biodiagnostics and Biotherapythe Second Affiliated Hospital of Xi’an Jiaotong University College of Medicine

Pancreatitis is an increasingly common and sometimes severe disease that lacks a specific therapy. The pathogenesis of pancreatitis is still not well understood. Calcium (Ca2+) is a versatile carrier of signals regulating many aspects of cellular activity and plays a central role in controlling digestive enzyme secretion in pancreatic acinar cells. Ca2+ overload is a key early event and is crucial in the pathogenesis of many diseases. In pancreatic acinar cells, pathological Ca2+ signaling (stimulated by bile, alcohol metabolites and other causes) is a key contributor to the initiation of cell injury due to prolonged and global Ca2+ elevation that results in trypsin activation, vacuolization and necrosis, all of which are crucial in the development of pancreatitis. Increased release of Ca2+ from stores in the intracellular endoplasmic reticulum and/or increased Ca2+ entry through the plasma membrane are causes of such cell damage. Failed mitochondrial adenosine triphosphate (ATP) production reduces re-uptake and extrusion of Ca2+ by the sarco/endoplasmic reticulum Ca2+-activated ATPase and plasma membrane Ca2+-ATPase pumps, which contribute to Ca2+ overload. Current findings have provided further insight into the roles and mechanisms of abnormal pancreatic acinar Ca2+ signals in pancreatitis. The lack of available specific treatments is therefore an objective of ongoing research. research is currently underway to establish the mechanisms and interactions of Ca2+ signals in the pathogenesis of pancreatitis.

关键词： Pancreatitis Calcium signaling Pancreatic acinar cells Overload Cell injury

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Perspectives of traditional Chinese medicine in pancreas protection for acute pancreatitis

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World Journal of Gastroenterology 2017年第20期23卷 3615-3623页

作者： Jun Li Shu Zhang Rui Zhou Jian Zhang Zong-Fang Li national local joint engineering research center of biodiagnostics and biotherapy the Second Affiliated Hospital of Xi'an Jiaotong University College of Medicine national local joint engineering research center of biodiagnostics and biotherapy Department of General Surgerythe Second Affiliated Hospital of Xi'an Jiaotong University College of Medicine

Acute pancreatitis(AP)is one of the most common *** is associated with significant morbidity and mortality,but it lacks specific and effective *** Chinese medicine(TCM)is one of the most popular complementary and alternative medicine modalities worldwide for the treatment of *** current evidence from basic research and clinical studies has shown that TCM has good therapeutic effects on *** review summarizes the widely used formulas,single herbs and monomers that are used to treat AP and the potential underlying mechanisms of *** of the abundance,low cost,and safety of TCM as well as its ability to target various aspects of the pathogenesis,TCM provides potential clinical benefits and a new avenue with tremendous potential for the future treatment of AP.

关键词： Acute pancreatitis Traditional Chinese medicine Alternative therapy Pancreas protection Anti-inflammatory

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Emodin and baicalein inhibit sodium taurocholate-induced vacuole formation in pancreatic acinar cells

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World Journal of Gastroenterology 2018年第1期24卷 35-45页

作者： jun li rui zhou bei-bei bie na huang ying guo hai-yan chen meng-jiao shi jun yang jian zhang zong-fang li national and local joint engineering research center of biodiagnostics and biotherapy the Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710004Shaanxi ProvinceChina

AIM To investigate the effects of combined use of emodin and baicalein(CEB) at the cellular and organism levelsin severe acute pancreatitis(SAP) and explore the underlying *** SAP was induced by retrograde infusion of 5% sodium taurocholate into the pancreatic duct in 48 male SD rats. Pancreatic histopathology score, serum amylase activity, and levels of tumour necrosis factor alpha(TNf-α), interleukin 6(IL-6), and IL-10 were determined to assess the effects of CEB at 12 h after the surgery. The rat pancreatic acinar cells were isolated from healthy male SD rats using collagenase. The cell viability, cell ultrastructure, intracellular free Ca2+ concentration, and inositol(1,4,5)-trisphosphate receptor(IP3 R) expression were investigated to assess the mechanism of *** Pancreatic histopathology score(2.07 ± 1.20 vs 6.84 ± 1.13, P 0.05).CONCLUSION These results at the cellular and organism levels reflect a preliminary mechanism of CEB in SAP and indicate that CEB is a suitable approach for SAP treatment.

关键词： inositol(1,4,5)-trisphosphate receptor Severe acute pancreatitis Calcium overload Emodin Baicalein Pancreatic acinar cell

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Acute diffuse peritonitis secondary to a seminal vesicle abscess:A case report

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World Journal of Clinical Cases 2023年第3期11卷 645-654页

作者： Kun Li Nan-Bin Liu Jiang-Xi Liu Quan-Ning Chen Bao-Min Shi Department of General Surgery Tongji Hospital of Tongji UniversityShanghai 200065China national and local joint engineering research center of Biodiagnosis and biotherapy The Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'an 710000Shaanxi ProvinceChina

BACKGROUND Seminal vesicle abscess(SVA)is the manifestation of a relatively rare urinary system *** response to urinary system inflammation,an abscess forms in special ***,acute diffuse peritonitis(ADP)induced by SVA is *** SUMMARY We report a case of a left SVA in a male patient complicated with pelvic abscess,ADP,multiple organ dysfunction syndrome,infectious shock,bacteremia,and acute appendiceal extraserous suppurative inflammation as a result of a long-term indwelling urinary *** patient received a course of morinidazole+cefminol antibiotics but showed no obvious relief,so the perineal SVA underwent puncture drainage and abdominal abscess drainage+appendectomy was *** operations were *** the operation,anti-infection,anti-shock,and nutritional support treatments were continued and various laboratory indicators were regularly *** patient was discharged from the hospital after *** disease is a challenge for the clinician because of the unusual spreading path of the ***,appropriate intervention and adequate drainage of abdominal and pelvic lesions are necessary,especially when the primary focus cannot be *** The etiology of ADP varies,but acute peritonitis secondary to SVA is very *** this patient,the left SVA not only affected the adjacent prostate and bladder but also spread retrogradely through the vas deferens,forming a pelvic abscess in the loose tissues of the extraperitoneal fascia *** involving the peritoneal layer led to ascites and pus accumulation in the abdominal cavity,and appendix involvement led to extraserous suppurative *** clinical practice,surgeons need to consider the results of various laboratory tests and imaging examinations to make comprehensive judgments involving the diagnosis and treatment plan.

关键词： Seminal vesicle abscess Acute diffuse peritonitis Acute appendicitis Multiple organ dysfunction syndrome Case report

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Mesenchymal stem cell-derived exosomes: A novel and potential remedy for cutaneous wound healing and regeneration

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World Journal of Stem Cells 2022年第5期14卷 318-329页

作者： Jia-Chen Hu Chen-Xi Zheng Bing-Dong Sui Wen-Jia Liu Yan Jin Key Laboratory of Military Stomatology and national Clinical research center for Oral Diseases and Shaanxi International joint research center for Oral Diseases Center for Tissue EngineeringSchool of StomatologyThe Fourth Military Medical UniversityXi’an 710032Shaanxi ProvinceChina national and local joint engineering research center of Biodiagnosis and biotherapy Precision Medicine InstituteInstitute for Stem Cell and Regenerative MedicineThe Second Affiliated HospitalXi’an Jiaotong UniversityXi’an 710032Shaanxi ProvinceChina

Poor healing of cutaneous wounds is a common medical problem in the field of *** to the intricate pathophysiological processes of wound healing,the use of conventional treatment methods,such as chemical molecule drugs and traditional dressings,have been unable to achieve satisfactory *** recent years,explicit evidence suggests that mesenchymal stem cells(MSCs)have great therapeutic potentials on skin wound healing and ***,the direct application of MSCs still faces many challenges and ***,exosomes as cell-secreted granular vesicles with a lipid bilayer membrane structure and containing specific components from the source cells may emerge to be excellent substitutes for *** derived from MSCs(MSC-exosomes)have been demonstrated to be beneficial for cutaneous wound healing and accelerate the process through a variety of *** mechanisms include alleviating inflammation,promoting vascularization,and promoting proliferation and migration of epithelial cells and ***,the application of MSC-exosomes may be a promising alternative to cell therapy in the treatment of cutaneous wounds and could promote wound healing through multiple mechanisms *** review will provide an overview of the role and the mechanisms of MSC-derived exosomes in cutaneous wound healing,and elaborate the potentials and future perspectives of MSC-exosomes application in clinical practice.

关键词： Mesenchymal stem cells Extracellular vesicles Exosomes Wound healing Skin regeneration

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Cocktail hepatocarcinoma therapy by a super-assembled nano-pill targeting XPO1 and ATR synergistically

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Journal of Pharmaceutical Analysis 2023年第6期13卷 603-615页

作者： Liuyun Gong Yinliang Lu Jing Wang Xinyue Li Jing Zhao Yuetong Chen Rongze Ma Jinlu Ma Tianya Liu Suxia Han Department of Radiation Oncology The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710061China national&local joint engineering research center of Biodiagnosis and biotherapy The Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710004China Department of Radiotherapy The First Affiliated Hospital Soochow UniversitySuzhouJiangsu215000China

Intensive cancer treatment with drug combination is widely exploited in the clinic but suffers from inconsistent pharmacokinetics among different therapeutic *** overcome it,the emerging nanomedicine offers an unparalleled opportunity for encapsulating multiple drugs in a ***,a two-step super-assembled strategy was performed to unify the pharmacokinetics of a peptide and a small molecular *** this proof-of-concept study,the bioinformatics analysis firstly revealed the potential synergies towards hepatoma therapy for the associative inhibition of exportin 1(XPO1)and ataxia telangiectasia mutated-Rad3-related(ATR),and then a super-assembled nano-pill(gold nano drug carrier loaded AZD6738 and 97110 amino acids of apoptin(AP)(AA@G))was constructed through camouflaging AZD6738(ATR small-molecule inhibitor)-binding human serum albumin onto the AP-Au supramolecular *** expected,both in vitro and in vivo experiment results verified that the AA@G possessed extraordinary biocompatibility and enhanced therapeutic effect through inducing cell cycle arrest,promoting DNA damage and inhibiting DNA repair of hepatoma *** work not only provides a co-delivery strategy for intensive liver cancer treatment with the clinical translational potential,but develops a common approach to unify the pharmacokinetics of peptide and small-molecular compounds,thereby extending the scope of drugs for developing the advanced combination therapy.

关键词： Liver cancer Drug combination Cancer therapy ATR inhibitor XPO1 inhibitor

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Intelligent nanoreactor coupling tumor microenvironment manipulation and H_(2)O_(2)-dependent photothermal-chemodynamic therapy for accurate treatment of primary and metastatic tumors

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Bioactive Materials 2024年第4期34卷 354-365页

作者： Jie Liu Tianfeng Yang Handan Zhang Lin Weng Xiuhong Peng Tao Liu Cheng Cheng Yanmin Zhang Xin Chen School of Chemical engineering and Technology Shaanxi Key Laboratory of Energy Chemical Process IntensificationInstitute of Polymer Science in Chemical EngineeringXi’an Jiaotong UniversityXi’an710049China School of Pharmacy Health Science CenterXi’an Jiaotong UniversityXi’an710061China national&local joint engineering research center of Biodiagnosis and biotherapy The Second Affiliated Hospital of Xi’an Jiaotong UniversityXi’an710004China

Tumor microenvironment(TME),as the“soil”of tumor growth and metastasis,exhibits significant differences from normal physiological ***,how to manipulate the distinctions to achieve the accurate therapy of primary and metastatic tumors is still a ***,an innovative nanoreactor(AH@MBTF)is developed to utilize the apparent differences(copper concentration and H_(2)O_(2)level)between tumor cells and normal cells to eliminate primary tumor based on H_(2)O_(2)-dependent photothermal-chemodynamic therapy and suppress metastatic tumor through copper *** nanoreactor is constructed using functionalized MSN incorporating benzoyl thiourea(BTU),triphenylphosphine(TPP),and folic acid(FA),while being co-loaded with horseradish peroxidase(HRP)and its substrate *** therapy,the BTU moieties on AH@MBTF could capture excessive copper(highly correlated with tumor metastasis),presenting exceptional anti-metastasis ***,the complexation between BTU and copper triggers the formation of cuprous ions,which further react with H_(2)O_(2)to generate cytotoxic hydroxyl radical(•OH),inhibiting tumor growth via che-modynamic ***,the stepwise targeting of FA and TPP guides AH@MBTF to accurately accu-mulate in tumor mitochondria,containing abnormally high levels of H_(2)O_(2).As a catalyst,HRP mediates the oxidation reaction between ABTS and H_(2)O_(2)to yield activated ABTS•^(+).Upon 808 nm laser irradiation,the activated ABTS•^(+)performs tumor-specific photothermal therapy,achieving the ablation of primary tumor by raising the tissue ***,this intelligent nanoreactor possesses profound potential in inhib-iting tumor progression and metastasis.

关键词： Nanoreactor H_(2)O_(2)-dependent Photothermal-chemodynamic therapy Copper depletion Tumor metastasis inhibition

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Bioactive antiinflammatory antibacterial hemostatic citrate-based dressing with macrophage polarization regulation for accelerating wound healing and hair follicle neogenesis

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Bioactive Materials 2021年第3期6卷 721-728页

作者： Wenguang Liu Min Wang Wei Cheng Wen Niu Mi Chen Meng Luo Chenxi Xie Tongtong Leng Long Zhang Bo Lei Frontier Institute of Science and Technology Xi'an Jiaotong UniversityXi'an710054PR China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine research College of StomatologyXi'an Jiaotong UniversityXi'an710000China national and local joint engineering research center of Biodiagnosis and biotherapy The Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710000China Instrument Analysis center Xi'an Jiaotong UniversityXi'an710054China

The efficient cutaneous wound healing accompanied with the enhanced skin appendage regeneration is still a *** bacterial infection and excessive/prolonged inflammation inhibit wound healing process and result in the scar ***,we reported an anti-inflammatory polycitrate-polyethyleneimine-Ibuprofen(PCEI)and multifunctional PCEI-based F127-ε-polypeptide-alginic(FEA)dressing(FEA-PCEI)for accelerating wound healing and hair follicle *** showed the excellent anti-inflammation function through stimulating macrophage towards anti-inflammatory M2 subtype *** FEA-PCEI dressing showed the temperature-response gelation,injectability,robust antibacterial activity,light-damage-resistant,homeostasis ability,and good *** optimized dosage of FEA-PCEI dressing could significantly accelerate wound healing with anti-infection ability,reduce the scar formation,and promote the hair follicle *** study provided a wound-repairing strategy through regulating the phenotype of immune cells by the designing bioactive multifunctional biomaterials.

关键词： Bioactive dressing Polycitrate Anti-inflammation Antibacterial Wound healing

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Aurora A Kinase Plays a Key Role in Mitosis Skip during Senescence Induced by Ionizing Radiation

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Biomedical and Environmental Sciences 2023年第10期36卷 903-916页

作者： ZHANG Xu Rui ZHANG Tong Shan ZHANG Ya Nan HUA Jun Rui WANG Ju Fang HE Jin Peng Key Laboratory of Space Radiobiology of Gansu Province&CAS Key Laboratory of Heavy Ion Radiation Biology and Medicine Institute of Modern PhysicsChinese Academy of SciencesLanzhou 730000GansuChina national-local joint engineering research center of Biodiagnostic&biotherapy The Second Affiliated HospitalXi’an Jiaotong UniversityXi’an 710004ShaanxiChina University of Chinese Academy of Sciences Beijing 100049China

Objective To investigate the fate and underlying mechanisms of G2 phase arrest in cancer cells elicited by ionizing radiation(IR).Methods Human melanoma A375 and 92-1 cells were treated with X-rays radiation or Aurora A inhibitor MLN8237(MLN)and/or p21 depletion by small interfering RNA(si RNA).Cell cycle distribution was determined using flow cytometry and a fluorescent ubiquitin-based cell cycle indicator(FUCCI)system combined with histone H3 phosphorylation at Ser10(p S10 H3)*** was assessed using senescence-associated-β-galactosidase(SA-β-Gal),Ki67,andγH2AX *** expression levels were determined using western *** Tumor cells suffered severe DNA damage and underwent G2 arrest after IR *** damaged cells did not successfully enter M phase nor were they stably blocked at G2 phase but underwent mitotic skipping and entered G1 phase as tetraploid cells,ultimately leading to senescence in *** this process,the p53/p21 pathway is *** p21 accumulation,Aurora A kinase levels declined *** treatment confirmed that Aurora A kinase activity is essential for mitosis skipping and senescence *** Persistent p21 activation during IR-induced G2 phase blockade drives Aurora A kinase degradation,leading to senescence via mitotic skipping.

关键词： Ionizing radiation Senescence G2 arrest Tetraploid Mitosis skipping

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Bioactive biodegradable polycitrate nanoclusters enhances the myoblast differentiation and in vivo skeletal muscle regeneration via p38 MAPK signaling pathway

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Bioactive Materials 2020年第3期5卷 486-495页

作者： Yi Guo Min Wang Juan Ge Wen Niu Mi Chen Wei Cheng Bo Lei Frontier Institute of Science and Technology Xi'an Jiaotong UniversityXi'an710054China Key Laboratory of Shaanxi Province for Craniofacial Precision Medicine research College of StomatologyXi'an Jiaotong UniversityXi'an710054China national and local joint engineering research center of Biodiagnosis and biotherapy The Second Affiliated Hospital of Xi'an Jiaotong UniversityXi'an710000China Instrument Analysis center Xi'an Jiaotong UniversityXi'an710054China Department of Biomedical engineering University of MichiganAnn ArborMI48109United States

Complete skeletal muscle repair and regeneration due to severe large injury or disease is still a *** cues are critical to control myoblast cell function and can be utilized to develop smart biomaterials for skeletal muscle *** acid-based biodegradable polymers have received much attention on tissue engineering,however,their regulation on myoblast cell differentiation and mechanism was few ***,we find that citrate-based polycitrate-polyethylene glycol-polyethylenimine(POCG-PEI600)nanoclusters can significantly enhance the in vitro myoblast proliferation by probably reinforcing the mitochondrial number,promote the myotube formation and full-thickness skeletal muscle regeneration in vivo by activating the myogenic biomarker genes expression of Myod and ***-PEI600 nanoclusters could also promote the phosphorylation of p38 in MAP kinases(MAPK)signaling pathway,which led to the promotion of the myoblast *** in vivo skeletal muscle loss rat model also confirmed that POCG-PEI600 nanoclusters could significantly improve the angiogenesis,myofibers formation and complete skeletal muscle ***-PEI600 nanocluster could be also biodegraded into small molecules and eliminated in vivo,suggesting their high biocompatibility and *** study could provide a bioactive biomaterial-based strategy to repair and regenerate skeletal muscle tissue.

关键词： Bioactive biomaterials Citrate nanopolymer Myoblast differentiation Skeletal muscle regeneration

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