Abstract Background : Ischemia reperfusion injury (IRI) is the major cause of intestinal damage in clinic. Although either mesenchymal stromal cells (MSCs) or interleukin 37 (IL-37) showed some beneficial roles to ameliorate IRI, their effects are limited. In this study, the protective effects of IL-37 gene-modified MSCs (IL-37-MSCs) for better prevention of intestinal IRI are investigated. Methods: Intestinal IRI model was established by occluding the superior mesenteric artery for 30min and then reperfusing for 72 hours in rats. Forty adult male SD rats were randomly divided into sham control, IL-37-MSC-treated, MSC-treated, recombinant IL-37 (rIL-37)-treated and untreated groups. Intestinal damage was assessed by H&E staining. The levels of gut barrier function factors (diamine oxidase and D-Lactate) and inflammation reactivity cytokine IL-1β were assayed by ELISA. The expressions of tissue damage-related NLRP3 inflammasome and relative proteins including clevead caspase-1, IL-1β and IL-18 were detected by western blot. As downstream of IL-1β and IL-18, the mRNA levels of proinflammatory mediators IL-6 and TNF-α were determined by qPCR. Data were analyzed by one-way analysis of variance among groups. Results : IL-37-MSCs were able to migrate to the damaged tissue and significantly inhibit intestinal IRI. As compared with MSCs or rIL-37 monotherapy group, IL-37-MSC treatment not only improved gut barrier function but also decreased local and systemic inflammation reactivity cytokine IL-1β level in IRI rats. In addition, tissue damage-related NLRP3 and relative proteins (cleaved caspase-1, IL-1β and IL-18) were significantly decreased in IRI rats treated with IL-37-MSCs. Furthermore, IL-1β and IL-18 related proinflammatory mediators IL-6 and TNF-α mRNA expressions were markedly decreased following IL-37-MSC treatment. Conclusion : The results suggest that IL-37 gene modification significantly enhance the protective effects of MSCs against intestinal IRI. In addition, NLRP3-related signaling pathways could be associated with IL-37-MSC mediated protection.
To explore the possibility of detergent acellularized porcine heart valve serving as a scaffold for tissue engineering valve.The porcine aortic valves were acellularized by use of trypsin-EDTA. Triton X-100, RNase and DNase treatment. Biomechanical characteristics of fresh valves and acellularized valve were tested; also fresh valves, acellularized valve and valves treated with method of bioprothetic treatment were implanted subcutaneously in rats; frequently seeded with bovine aortic endothelial cells(BAECs), and then cultured for 7 days.The acellularization procedure resulted in complete removal of the cellular components while the construction of matrix was maintained. The matrix could be successfully seeded with in vitro expanded BAECs, which formed a continuous monolayer on the surface. There is no significant difference of PGI2 secretion of BAECs between cells seeded onto the acellular leaflets and that onto the wells of 24-wells plate (P > 0.05).Acellularied porcine aortic valve can be applied as a scaffold to develop tissue engineering heart valve.
To elucidate the early and long-term results of surgical treatment for complex infective endocarditis with prosthetic valve replacement.Fifty-seven patients of complex native valve endocarditis, including 25 cases of aortic valve, 16 of mitral valve and 16 of double valves, who underwent operative interventions with prosthetic valve replacement between December 1988 and June 2002, were analyzed retrospectively. Intraoperative findings demonstrated aortic annular abscesses (n = 19), root abscesses (n = 4), mitral posterior annular abscesses (n = 11), myocardial abscesses (n = 6), massive leaflet destruction (n = 32) and valvular vegetations (n = 55). Complex reconstruction of the aortic and mitral annulus was required in 35 patients. Associated procedures included Bentall's procedure (n = 4), aortic valve replacement (n = 21), mitral valve replacement (n = 16) and double valve replacements (n = 16).The operative mortality was 11%. Complications included low cardiac output syndrome, recurrence of endocarditis, multiple organ failure, ventricular arrhythmia, bleeding, mediastinal infection, respiratory insufficiency and heart block. Follow-up was 100% complete at a mean of 5.93 years. There were five late deaths (3 prosthetic valve endocarditis, 2 valve-related). The NYHA functional status recovered to Class I in 17 patients, Class II in 27 and Class III in 2 at 1 year follow-up. Kaplan-Meier analysis showed the 5-year actuarial freedom from reoperation was (84 +/- 3)%, and actuarial survivorship at 5 years was (61 +/- 9)%.Urgent or even emergency operation is advocated for complex infective endocarditis. Proper intraoperative reconstruction of the aortic and mitral annulus and optimized perioperative management, especially the strategy for prevention of recurrent endocarditis, are of great importance in achieving satisfied early and long-term clinical outcomes.
The endometrial regenerative cell (ERC) is a novel type of adult mesenchymal stem cell isolated from menstrual blood. Previous studies demonstrated that ERCs possess unique immunoregulatory properties in vitro and in vivo, as well as the ability to differentiate into functional hepatocyte-like cells. For these reasons, the present study was undertaken to explore the effects of ERCs on carbon tetrachloride (CCl4)-induced acute liver injury (ALI).An ALI model in C57BL/6 mice was induced by administration of intraperitoneal injection of CCl4. Transplanted ERCs were intravenously injected (1 million/mouse) into mice 30 min after ALI induction. Liver function, pathological and immunohistological changes, cell tracking, immune cell populations and cytokine profiles were assessed 24 h after the CCl4 induction.ERC treatment effectively decreased the CCl4-induced elevation of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities and improved hepatic histopathological abnormalities compared to the untreated ALI group. Immunohistochemical staining showed that over-expression of lymphocyte antigen 6 complex, locus G (Ly6G) was markedly inhibited, whereas expression of proliferating cell nuclear antigen (PCNA) was increased after ERC treatment. Furthermore, the frequency of CD4+ and CD8+ T cell populations in the spleen was significantly down-regulated, while the percentage of splenic CD4+CD25+FOXP3+ regulatory T cells (Tregs) was obviously up-regulated after ERC treatment. Moreover, splenic dendritic cells in ERC-treated mice exhibited dramatically decreased MHC-II expression. Cell tracking studies showed that transplanted PKH26-labeled ERCs engrafted to lung, spleen and injured liver. Compared to untreated controls, mice treated with ERCs had lower levels of IL-1β, IL-6, and TNF-α but higher level of IL-10 in both serum and liver.Human ERCs protect the liver from acute injury in mice through hepatocyte proliferation promotion, as well as through anti-inflammatory and immunoregulatory effects.
Objective To analyze the clinical data and therapeutic efficacy for heart valve replacement (HVR) after closed mitral commissurotomy with rheumatic heart disease. Methods Thirty four patients with HVR after closed mitral commissurotomy from August 2001 to July 2002 in Changhai hospital were recruited. The average interval between the two operations was 4-29(12.6±6.73)years. Two of them (5.9%) received mitral valve replacement (MVR), 16 cases (47.1%) had MVR and tricuspid valvuloplasty (TVP De-vega), 2 cases (5.9%) had double (aortic and mitral) valve replacement (DVR), 14 cases (41.2%) had DVR and TVP. Cross-check analysis was done with 257 HVR patients at cotemporary. Results There was no obviously difference in the HVR after closed mitral commissurotomy patients compare with HVR at cotemporary in sex, age, heart function, modus operandi, the CPB, the time of aortic blockage, early postoperative mortality, etc. Conclusion Closed mitral commissurotomy corrected the function of pathological mitral valve, but the proceeding of disease was not changed. They must be operated as soon as possible if the patient's condition aggravation after closed mitral commissurotomy.
OBJECTIVE To investigate the role of protein kinase C(PKC) in mediation of ischemic preconditioning(IPC) against myocardial reperfusion injury by using PKC inhibitor polymyxin B(Poly B) and PKC activator 4β-phorbol-12-myristate-13-acetate(PMA) during cardiopulmonary bypass(CPB) in feline.METHODS One hundred and twenty felines were randomized into five groups: control group(n=24),in which CPB was conducted without aortic cross-clamping(ACC);IR group(n=24),with 60 min cardiac arrest by ACC followed by 30 min reperfusion,and cardioplegia used during the period of ACC;IPC group(n=24),with protocol similar to that of IR group except for three-round 15 min IPC applied before ACC;Poly B group(n=24),with protocol similar to that of IPC group except for polymyxin B administered after starting of IPC;PMA group(n=24),with protocol similar to that of IR group except for PMA administered before ACC.Membrane and cytosol fraction of PKC activity was assessed by biochemical assays,and myocardial Ca~(2+)content was determined simultaneously.RESULTS PKC activity in both membrane and cytosol fractions was significantly reduced after 60 min cardiac arrest with ACC and during myocardial reperfusion in IR group while the Ca~(2+)content in myocardium was significant increased.However,IPC enhanced the activation and translocation of PKC to the membrane and significantly reduced the rise in myocardial Ca2 +content.Although mem-brane and cytosol fraction of PKC activity were also both inhibited by Poly B after ACC,the increase ofmyocardial Ca2 +contentwas markedly attenuated which was comparable with thatin IPC group,whereasthe change patterns of PKC activities and myocardial Ca2 +content were similar to IPC in PMA group.CONCLUSION Cardioprotection by IPC is mediated through enhanced translocation of PKC to the membrane.PKC in-hibitor Poly B cannot completely abolish IPC-induced cardioprotection.PKC activator PMA mimics at least partially theprotective effect of IPC against myocardial calcium overload.
[Objective] To verify the adhesion and growth ability of human esophageal epithelial cells(HEECs) on poly(lactic-co-glycolic acid)(PLGA), a three-dimensional biodegradable polymer scaffold, and to reconstruct human esophagus by tissue engineering. [Methods] HEECs isolated from adult esophagi resected in esophagectomy were seeded onto PLGA scaffold after expansion by in vitro culture. The complex of cell-scaffold were then cultured ex vivo and transplanted to subcutaneous of nude mouse respectively. The cell-seeded scaffolds in different culture intervals were assessed by histological staining of H-E. Scanning electron microscopy was utilized to verify the interactions between the cells and the biomaterial. Immunohistochemical analyses was also performed to evaluate cytokeratin. [Results] HEECs were well distributed and adhered to PLGA scaffolds and maintained their characteristics throughout the culture period. Both the first passaged esophageal epithelial cells and seeded cells could express and product cytokeratin. After cultured in vivo for 4 weeks the cell-seeded scaffolds grew like tissues. [Conclusions] PLGA scaffolds can support the esophageal epithelial cells'proliferation, and can be suitable carrier for tissue engineering of artificial esophagus.
Abstract Background We have demonstrated that endometrial regenerative cells (ERCs) are mesenchymal-like stromal cells and can attenuate experimental colitis, however, its underlying mechanism needs further investigation. Dickkopf-1 (DKK1), a glucoprotein secreted by mesenchymal stromal cells (MSCs), is a classical inhibitor of Wnt/β-catenin pathway which is closely associated with the development of colitis. Therefore, the objective of this study was to investigate whether ERCs could also secret DKK1, and whether the downregulation of DKK1 (DKK1 low -ERCs) would enhance the therapeutic effects of ERCs in attenuation of experimental colitis. Methods BALB/c mice were given 3% dextran sodium sulfate (DSS) for 7 consecutive days and free tap water for 3 days sequentially to induce experimental colitis. Unmodified ERCs, IL-1β-treated ERCs (DKK1 low -ERCs) and glucocorticoid-treated ERCs (DKK1 high -ERCs) were injected (1 million/mouse/day, i.v. ) on day 2, 5 and 8 respectively. Colonic and splenic samples were harvested on day 10 after DSS-induction. Results It was found that DKK1 low -ERC treatment markedly attenuated colonic damage, body weight loss and colon-length shortening in colitis mice. Compared with other treatments, cell populations of CD4 + IL-4 + Th2, CD4 + CD25 + FOXP3 + Treg, and CD68 + CD206 + macrophages in spleens were also significantly upregulated in DKK1 low -ERC group ( p < 0.05). In addition, lower expression of pro-inflammatory (TNF-α and IFN-γ), but higher levels of anti-inflammatory cytokines (IL-4 and IL-10) and β-catenin were detected in colons in DKK1 low -ERC group ( p < 0.01 vs. other groups). Conclusions DKK1 low -ERCs display augmented immunoregulatory ability and therapeutic effects in DSS-induced colitis.
To study the changes in pathogenic causes and the prognosis of aortic valve replacement (AVR).The clinical data of 1026 patients undergoing AVR from December 1980 to December 2006 were analyzed retrospectively. The mortality, morbidity, changes in pathogenic causes and risk factors were analyzed.The postoperative mortality and complication morbidity were 4.3% and 10.6% respectively within 30 days followed operation. Main causes of operative death were heart failure, multi organ failure and endocarditis. The major risk factors for operative death were left ventricle ejection fraction less than 0.4, endocarditis, valve regurgitation and emergency operation before AVR. Late mortality was 0.54% patient-year (3.4%), most of whom died of heart failure, endocarditis and arrhythmias. Patients underwent reoperation 0.22% patient-year (1.4%), with the causes of endocarditis and perivalvular fistula.Morbidity of rheumatic damage in aortic valve has decreased, while valve degeneration has increased gradually in the recent years. Avoiding prosthesis-patient mismatch, good postoperatively guide and prevention of endocarditis can improve the prognosis of AVR.
'/%3e%3cuse xlink:href='%23a' transform='rotate(23.036 .093 25.536)'/%3e%3cuse xlink:href='%23a' transform='rotate(45.87 1.273 16.18)'/%3e%3cuse xlink:href='%23a' transform='rotate(69.945 .996 12.078)'/%3e%3cuse xlink:href='%23a' transform='rotate(20.66 -19.689 31.932)'/%3e%3c/svg%3e)