construction-multilayered-mesenchymal-stem-cell-sheet-with-3d-dynamic

Construction of a Multilayered Mesenchymal Stem Cell Sheet with a 3D Dynamic Culture System

Stem cell therapy shows a promising future in regenerating injured organ and tissues, and the cell sheet technique has been developed to improve the low ...

prognostic-analysis-butylphthalide-therapy-guided-cyp2c19-genotype

Prognostic Analysis of Butylphthalide Therapy Guided by CYP2C19 Genotype in Patients with Acute Cerebral Infarction

To investigate the prognosis of patients with acute-phase cerebral infarction treated with butylphthalide based on cytochrome P450 2C19 (CYP2C19) ...

First Affiliated Hospital of Jinan University

Shaoxing University

The aim of the present study was to explore the effect of adherence to standardized administration of anti-platelet drugs on the prognosis of patients with coronary heart disease. A total of 144 patients newly diagnosed with coronary heart disease at Lu'an Shili Hospital of Anhui Province (Lu'an, China) between June 2010 and June 2012 were followed up. Kaplan-Meier curves and the Cox regression model were used to evaluate the effects of standardized administration of anti-platelet drugs on primary and secondary end-point events. Of the patients with coronary heart disease, 109 (76%) patients took standard anti-platelet drugs following discharge. Kaplan-Meier curve and Cox regression analysis showed that standardized administration of anti-platelet drugs reduced the risk of primary end-point events (including all-cause mortality, non-lethal myocardial infarction and stroke) of patients with coronary heart disease [hazard ratio (HR)=0.307; 95% confidence interval (CI): 0.099-0.953; P=0.041) and all-cause mortality (HR=0.162; 95% CI: 0.029-0.890; P=0.036); however, standardized administration had no predictive value with regard to secondary end-point events. Standardized administration of anti-platelet drugs obviously reduced the risk of primary end-point events in patients with coronary heart disease, and further analysis showed that only all-cause mortality exhibited a statistically significant reduction.

Investigation of standardized administration of anti-platelet drugs and its effect on the prognosis of patients with coronary heart disease.

Cell sheet techniques offer a promising future for myocardial infarction (MI) therapy; however, insufficient nutrition supply remains the major limitation in maintaining stem cell bioactivity in vitro. In order to enhance cell sheet mechanical strength and bioactivity, a decellularized porcine pericardium (DPP) scaffold was prepared by the phospholipase A2 method, and aspartic acid was used as a spacer arm to improve the vascular endothelial growth factor crosslink efficiency on the DPP scaffold. Based on this scaffold, multilayered bone marrow mesenchymal stem cell sheets were rapidly constructed, using RAD16-I peptide hydrogel as a temporary 3D scaffold, and cell sheets were cultured in either the 3D-dynamic system (DCcs) or the traditional static condition (SCcs). The multilayered structure, stem cell bioactivity, and ultrastructure of DCcs and SCcs were assessed. The DCcs exhibited lower apoptosis, lower differentiation, and an improved paracrine effect after a 48 h culture in vitro compared to the SCcs. Four groups were set to evaluate the cell sheet effect in rat MI model: sham group, MI control group, DCcs group, and SCcs group. The DCcs group improved cardiac function and decreased the infarcted area compared to the MI control group, while no significant improvements were observed in the SCcs group. Improved cell survival, angiogenesis, and Sca-1 cell and c-kit cell amounts were observed in the DCcs group. In conclusion, the DCcs maintained higher stem cell bioactivity by using the 3D-dynamic system to provide sufficient nutrition, and transplanting DCcs significantly improved the cardiac function and angiogenesis.

Preparation of high bioactivity multilayered bone-marrow mesenchymal stem cell sheets for myocardial infarction using a 3D-dynamic system.

Cardiospheres (CSps) are a promising new form of cardiac stem cells with advantage over other stem cells for myocardial regeneration, but direct implantation of CSps by conventional routes has been limited due to potential embolism. We have implanted CSps into the pericardial cavity and systematically demonstrated its efficacy regarding myocardial infarction. Stem cell potency and cell viability can be optimized in vitro prior to implantation by pre-conditioning CSps with pericardial fluid and hydrogel packing. Transplantation of optimized CSps into the pericardial cavity improved cardiac function and alleviated myocardial fibrosis, increased myocardial cell survival and promoted angiogenesis. Mechanistically, CSps are able to directly differentiate into cardiomyocytes in vivo and promote regeneration of myocardial cells and blood vessels through a paracrine effect with released growth factors as potential paracrine mediators. These findings establish a new strategy for therapeutic myocardial regeneration to treat myocardial infarction.

Pericardial application as a new route for implanting stem-cell cardiospheres to treat myocardial infarction.

Human enterovirus 71 (EV-71) is the main etiologic agent of hand, foot and mouth disease (HFMD). We sought to identify EV-71 specific antigens and develop serologic assays for acute-phase EV-71 infection. A series of truncated proteins within the N-terminal 100 amino acids (aa) of EV-71 VP1 was expressed in Escherichia coli. Western blot (WB) analysis showed that positions around 11-21 aa contain EV-71-specific antigenic sites, whereas positions 1-5 and 51-100 contain epitopes shared with human coxsackievirus A16 (CV-A16) and human echovirus 6 (E-6). The N-terminal truncated protein of VP1, VP₁₆₋₄₃, exhibited good stability and was recognized by anti-EV-71 specific rabbit sera. Alignment analysis showed that VP₁₆₋₄₃ is highly conserved among EV-71 strains from different genotypes but was heterologous among other enteroviruses. When the GST-VP₁₆₋₄₃ fusion protein was incorporated as antibody-capture agent in a WB assay and an ELISA for detecting anti-EV-71 IgM in human sera, sensitivities of 91.7% and 77.8% were achieved, respectively, with 100% specificity for both. The characterized EV-71 VP1 protein truncated to positions 6-43 aa has potential as an antigen for detection of anti-EV-71 IgM for early diagnosis of EV-71 infection in a WB format.

Identification of specific antigenic epitope at N-terminal segment of enterovirus 71 (EV-71) VP1 protein and characterization of its use in recombinant form for early diagnosis of EV-71 infection.

A latex agglutination test (LAT) was developed for the rapid detection of antibodies against the VP1 or VP1 proteins of Enterovirus 71 (EV71). The proteins of interest including prokaryotically expressed VP1 and two strains of anti-VP1 monoclonal antibody (McAb) against EV71 were covalently linked to carboxylated latex using ethyl-dimethyl-amino-propyl carbodiimide (EDC) to prepare sensitized latex beads. LAT was evaluated by an enzyme-linked immunosorbent assay (ELISA) as a reference test. The VP1-LAT showed a sensitivity of 87.0%, specificity of 88.9%, and an agreement ratio of 90.0% in detecting VP1 in 100 serum samples from experimentally infected mice, whereas these values were 86.8, 96.7, and 93.3%, respectively, for 608 clinical human serum samples. The VP1-LAT has advantages over other assays in terms of low cost, rapidity, chemical stability, high sensitivity, repeatability, and specificity. The LAT established in the present study is a rapid and simple test suitable for field monitoring of antibodies against VP1-EV71.

Development of a Specific Latex Agglutination Test to Detect Antibodies of Enterovirus 71.

Human enterovirus 71 (EV-A71) is one of the main etiological agents of hand, foot, and mouth disease (HFMD), which has been prevalent mainly in the Asia-Pacific region in the past several decades. The nonstructural proteins of EV-A71 will be expressed significantly during viral replication in host cells after EV-A71 infection. For the determination of the antibodies response against nonstructural proteins of EV-A71, in this study, the complete 2ABC, 3ABC, and 3D proteins were expressed in Escherichia coli and were then studied for their immunoreactivity by immunoblot assay and indirect enzyme-linked immunosorbent assay (ELISA), respectively. Three His-tagged fusion proteins were expressed effectively in E. coli, which were in agreement with the expected molecular mass. The results from immunoblot assay and indirect ELISA showed that all three purified fusion proteins can react with IgG antibodies from EV-A71-infected patients, but can hardly be recognized by IgG antibodies derived from mice or rabbits immunized by inactivated EV-A71 virus particles. The IgG antibody response against nonstructural proteins of EV-A71 is associated with viral infection or replication, which indicate that these nonstructural proteins could be used as candidate antigen for early diagnosis of EV-A71 infection, or to distinguish the EV-A71-specific antibodies after viral infection from inactivated vaccine immunization.

Immunoreactivity Analysis of the Nonstructural Proteins of Human Enterovirus 71.

Enterovirus 71 (EV-A71) has attracted widespread attention in the past decade because of its higher neurotropicity in addition to causing hand-foot-and-mouth disease (HFMD). Mapping epitopes of viral proteins may promote our understanding of antiviral humoral immunity, and is useful for clinical application. In this study, the linear B cell epitopes within nonstructural proteins of EV-A71 were identified using bioinformatics methods combined with peptide enzyme-linked immunosorbent assay (ELISA). Twenty epitopes were predicted and located at 2ABC (7), 3ABC (5), and 3D (8) protein, respectively. Of 20 epitope-containing peptides, 14 were verified by ELISA (S/CO >2.1), 9 of which had higher reactivity (S/CO >5.0). Furthermore, synthetic peptide SP09 (EV-A71-3ABC) can react with healthy children sera, and its immunoreactivity was closest to that of EV-A71-VP1 protein. The protein BLAST analysis revealed that SP09 may contain a common epitope due to the high homology of amino acid sequences with other members of human Enterovirus species A. These findings may be useful in the development serological tests for the diagnosis of HFMD caused by a broad range of human Enterovirus species A.

Screening and Identification of Linear B Cell Epitopes Within the Nonstructural Proteins of Enterovirus 71.

 Biliary tract infection (BTI) is a common complication in patients with biliary obstruction caused by various biliary tract disorders. To improve the management of patients with BTI, microbial profiles from bile cultures and antibiotic resistance patterns were evaluated in this six-year retrospective study.  A total of 709 patients with various biliary tract disorders from January 2012 to December 2017 were enrolled in this study. Bile specimens were taken from intra-operative puncture or post-operative drainage for microbial culture under sterile conditions. Microbial culture, identification, and antibiotic resistance test were performed according to a standard routine.  Cultures were positive in 574 of 789 bile specimens (73%). Of all isolates, 386 were gram-negative bacilli (67%), 170 were gram-positive cocci (30%), and 18 were fungi (3%). The two most common micro-organisms were  (29%) and  (16%), the extended-spectrum β-lactamases (ESBL) positivity rates of which were 52% and 21%, respectively. Both bacteria were highly resistant to commonly used antibiotic agents (penicillins, cephalosporins, and quinolones), and highly susceptible to carbapenems, amikacin, and piperacillin-tazobactam.  (19%) was the next most common bacteria isolated from bile samples, mainly including  (8%) and  (6%). These two bacteria were resistant to cefazolin and clindamycin but sensitive to teicoplanin, tigecycline, and vancomycin.  was more resistant than  to most of the tested antibiotic agents. Annual statistical analysis showed that the frequency of gram-negative enteric bacteria was decreasing slowly, but that of gram-positive enterococci was increasing slowly. Moreover, the overall antibiotic resistance rates of the most common strains have been decreasing slowly over the past six years.   ( and ) and  ( and ) were the common pathogenic bacteria causing BTI, which exhibited high resistance to routinely used antibiotic agents and were highly sensitive to piperacillin-tazobactam, carbapenem, amikacin, and vancomycin. The microbial profiles from bile and its antibiotic resistance patterns have changed, which will help in the empirical treatment of BTI.

Changes in Microbial Profiles and Antibiotic Resistance Patterns in Patients with Biliary Tract Infection over a Six-Year Period.

Alternate wetting and drying (AWD) irrigation has been widely used to save irrigation water during rice production when compared to the traditionally continuous flooding (CF). Although the influence of AWD on water-saving potential and grain yield has been studied before, its detailed effect on grain nutritional quality in milled rice remains relatively unexplored. In this study, AWD could maintain grain yield as compared with CF. Thus, we undertook efforts to compare the nutritional traits of milled rice irrigated with AWD and CF regimes. A targeted metabolome assay on milled rice identified 74 differentially accumulated metabolites (DAMs) with 22 up- and 52 down-accumulated metabolites under AWD vs. CF. Clustering of the metabolite content obtained in this assay suggested that most of the metabolites showing significant changes belonged to "lipids," "alkaloids," and "phenolic acids." In addition, total protein, starch, lipid, and amino acids content were measured to correlate it with the differential accumulation of specific metabolites detected in the metabolome. Overall, the data suggested that AWD may improve the nutritional performance of milled rice by increasing amino acids and phenolic acids and decreasing lipids and alkaloids. Our study provides research proof for the need for the optimization of irrigation to optimize rice nutritional qualities.

Effect of Alternate Wetting and Drying Irrigation on the Nutritional Qualities of Milled Rice.

Idiopathic pulmonary fibrosis (IPF) is a group of chronic interstitial pulmonary diseases characterized by an inexorable decline in lung function with limited treatment options. The abnormal expression of transforming growth factor-β (TGF-β) in profibrotic macrophages is linked to severe pulmonary fibrosis, but the regulation mechanisms of TGF-β expression are incompletely understood. We found that decreased expression of E3 ubiquitin ligase  in peripheral blood mononuclear cells (PBMCs) was significantly related to the severity of pulmonary fibrosis in IPF patients. Fbxw7 is identified to be a crucial suppressing factor for pulmonary fibrosis development and progression in a mouse model induced by intratracheal bleomycin treatment. Myeloid cell-specific  deletion increases pulmonary monocyte-macrophages accumulation in lung tissue, and eventually promotes bleomycin-induced collagen deposition and progressive pulmonary fibrosis. Notably, the expression of TGF-β in profibrotic macrophages was significantly upregulated in myeloid cell-specific  deletion mice after bleomycin treatment. C-Jun has long been regarded as a critical transcription factor of , we clarified that Fbxw7 inhibits the expression of TGF-β in profibrotic macrophages by interacting with c-Jun and mediating its K48-linked ubiquitination and degradation. These findings provide insight into the role of Fbxw7 in the regulation of macrophages during the pathogenesis of pulmonary fibrosis.

Myeloid Fbxw7 Prevents Pulmonary Fibrosis by Suppressing TGF-β Production.

To explore the application value of virtual autopsy to obtain key evidence information on drowned corpses and its application value of virtual autopsy in the diagnosis of drowning.

Virtual Autopsy Morphological Features of Drowning.

Human endogenous retroviruses (HERVs) are estimated to comprise ∼8% of the entire human genome, but the vast majority of them remain transcriptionally silent in most normal tissues due to accumulated mutations. However, HERVs can be frequently activated and detected in various tissues under certain conditions. Nucleic acids or proteins produced by HERVs can bind to pattern recognition receptors of immune cells or other cells and initiate an innate immune response, which may be involved in some pathogenesis of diseases, especially cancer and autoimmune diseases. In this review, we collect studies of the interaction between HERV elements and Toll-like receptors and attempt to provide an overview of their role in the immunopathological mechanisms of inflammatory and autoimmune diseases.

Human Endogenous Retroviruses and Toll-Like Receptors.

The normal autophagy flux is beneficial for the rapid elimination of phagocytic pathogens by macrophages. However, Mycobacterium tuberculosis interferes with the autophagy flux of macrophages to weaken their immune function and evade immune surveillance. In this study, we found that miRNA-215-5p was downregulated in tuberculosis patients. A potential diagnostic model for tuberculosis was established by combining miRNA-215-5p with three others differentially expressed microRNAs (miRNA-145-5p, miRNA-486-5p and miRNA-628-3p). Furthermore, we discovered that the up-regulated miRNA-215-5p could inhibit the maturation of autophagy by preventing the fusion of autophagosomes with lysosomes in macrophages. The role of TB-specific miRNA-215-5p in inhibiting auto-lysosome formation provides evidence of its potential role in Host-directed therapy for tuberculosis.

Pulmonary tuberculosis biomarker miR-215-5p inhibits autophagosome-lysosome fusion in macrophages.

To investigate whether menopausal status modifies the association between magnesium intake and migraine in women, hypothesizing that hormonal differences between pre-menopausal and post-menopausal women would result in differential responses to magnesium intake.

ArticleTotal : 2	Year
Publication title Cited by 2	2018
Publication title	2026

Article	Year
Investigation of standardized administration of anti-platelet drugs and its effect on the prognosis of patients with coronary heart disease. Experimental and therapeutic medicine\| PubMed ID: 28966689	2017
Preparation of high bioactivity multilayered bone-marrow mesenchymal stem cell sheets for myocardial infarction using a 3D-dynamic system. Acta biomaterialia\| PubMed ID: 29627677	2018
Pericardial application as a new route for implanting stem-cell cardiospheres to treat myocardial infarction. The Journal of physiology\| PubMed ID: 29736937	2018
Identification of specific antigenic epitope at N-terminal segment of enterovirus 71 (EV-71) VP1 protein and characterization of its use in recombinant form for early diagnosis of EV-71 infe... Virus research\| PubMed ID: 24952304	2014
Development of a Specific Latex Agglutination Test to Detect Antibodies of Enterovirus 71. Archives of medical research\| PubMed ID: 26363276	2015
Immunoreactivity Analysis of the Nonstructural Proteins of Human Enterovirus 71. Viral immunology\| PubMed ID: 27870604	2017
Screening and Identification of Linear B Cell Epitopes Within the Nonstructural Proteins of Enterovirus 71. Viral immunology\| PubMed ID: 30523737	2019
Changes in Microbial Profiles and Antibiotic Resistance Patterns in Patients with Biliary Tract Infection over a Six-Year Period. Surgical infections\| PubMed ID: 31017560	2019
Effect of Alternate Wetting and Drying Irrigation on the Nutritional Qualities of Milled Rice. Frontiers in plant science\| PubMed ID: 34567035	2021
Myeloid Fbxw7 Prevents Pulmonary Fibrosis by Suppressing TGF-β Production. Frontiers in immunology\| PubMed ID: 35069531	2021
Virtual Autopsy Morphological Features of Drowning. Fa yi xue za zhi\| PubMed ID: 35725704	2022
Human Endogenous Retroviruses and Toll-Like Receptors. Viral immunology\| PubMed ID: 36251943	2023
Pulmonary tuberculosis biomarker miR-215-5p inhibits autophagosome-lysosome fusion in macrophages. Tuberculosis (Edinburgh, Scotland)\| PubMed ID: 37925930	2023
Association Between Magnesium Intake and Migraine Among Pre and Postmenopausal Women: A Cross-Sectional Study. International journal of women's health\| PubMed ID: 40904698	2025

Jianhua Zhang

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