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Pulmonary fibrosis (PF) is a progressive, non-reversible illness with various etiologies. Currently, effective treatments for fibrotic lungs are still lacking. Here, we compared the effectiveness of transplantation of human mesenchymal stem cells from umbilical cord Wharton's jelly (HUMSCs) versus those from adipose tissue (ADMSCs) in reversing pulmonary fibrosis in rats. Bleomycin 5 mg was intratracheally injected to establish a severe, stable, single left lung animal model with PF. On Day 21 post-BLM administration, one single transplantation of 2.5 × 107 HUMSCs or ADMSCs was performed. Lung function examination of Injury and Injury+ADMSCs rats displayed significantly decreased blood oxygen saturation and increased respiratory rates, while Injury+HUMSCs rats showed statistical amelioration in blood oxygen saturation and significant alleviation in respiratory rates. Reduced cell number in the bronchoalveolar lavage and lower myofibroblast activation appeared in the rats transplanted with either ADMSCs or HUMSCS than that in the Injury group. However, ADMSC transplantation stimulated more adipogenesis. Furthermore, matrix-metallopeptidase-9 over-expression for collagen degradation, and the elevation of Toll-like receptor-4 expression for alveolar regeneration were observed only in the Injury+HUMSCs. In comparison with the transplantation of ADMSCs, transplantation of HUMSCs exhibited a much more effective therapeutic effect on PF, with significantly better results in alveolar volume and lung function.
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Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Fibrose Pulmonar , Geleia de Wharton , Humanos , Ratos , Animais , Fibrose Pulmonar/terapia , Fibrose Pulmonar/metabolismo , Cordão Umbilical , Transplante Heterólogo , Células-Tronco Mesenquimais/metabolismo , Transplante de Células-Tronco Mesenquimais/métodosRESUMO
Plasma and tissue zinc ion levels are associated with the development of obesity. Previous studies have suggested that zinc ions may regulate adipocyte metabolism and that nitric oxide (NO) plays a pivotal role in the regulation of adipocyte physiology. Our previous study showed that chronic NO deficiency causes a significant decrease in adipose tissue mass in rats. Studies also suggested that zinc ions play an important modulatory role in regulating NO function. This study aims to explore the role of zinc ions in NO-regulated adipocyte differentiation. We hypothesized that NO could increase intracellular Zn2+ level and then stimulate adipocyte differentiation. ZnCl2 and the NO donor, NONOate, were used to explore the effects of Zn2+ and NO on adipocyte differentiation. Regulatory mechanisms of NO on intracellular Zn2+ mobilization were determined by detection. Then, Zn2+-selective chelator TPEN was used to clarify the role of intracellular Zn2+ on NO-regulated adipocyte differentiation. Furthermore, the relationship between adipocyte size, Zn2+ level, and NOS expression in human subcutaneous fat tissue was elucidated. Results showed that both ZnCl2 and NO stimulated adipocyte differentiation in a dose-dependent manner. NO stimulated intracellular Zn2+ mobilization in adipocytes through the guanylate cyclase (GC)/cyclic guanosine monophosphate (cGMP)/protein kinase G (PKG) pathway, and NO-stimulated adipocyte differentiation was Zn2+-dependent. In human subcutaneous adipose tissue, adipocyte size was negatively correlated with expression of eNOS. In conclusion, NO treatment stimulates intracellular Zn2+ mobilization through the GC/cGMP/PKG pathway, subsequently stimulating adipocyte differentiation.
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Adipócitos , Proteínas Quinases Dependentes de GMP Cíclico , GMP Cíclico , Guanilato Ciclase , Óxido Nítrico , Zinco , Adipócitos/citologia , Adipócitos/metabolismo , Animais , GMP Cíclico/metabolismo , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Guanilato Ciclase/metabolismo , Óxido Nítrico/metabolismo , Ratos , Transdução de Sinais , Zinco/metabolismoRESUMO
Introduction: Peritoneal dialysis (PD) is a kind of renal replacement therapy for end-stage renal disease (ESRD). While PD has many advantages, various complications may arise. Methods: This retrospective study analyzed the complications of ESRD patients who received PD catheter implantation in a single medical center within 15 years. Results: This study collected 707 patients. In the first 14 days after PD implantation, 54 patients experienced bleeding complications, while 47 patients experienced wound infection. Among all complications, catheter-related infections were the most common complication 14 days after PD implantation (incidence: 38.8%). A total of 323 patients experienced PD catheter removal, of which 162 patients were due to infection, while 96 were intentional due to kidney transplantation. Excluding those whose catheters were removed due to transplantation, the median survival of the PD catheter was 4.1 years; among them, patients without diabetes mellitus (DM) were 7.4 years and patients with DM were 2.5 years (p < 0.001). Further, 50% probability of surviving was beyond 3.5 years in DM patients with HbA1CC < 7 and 1.6 years in DM patients with HbA1C <7 (p ≥ 0.001). Conclusions: Catheter-related infections were the most common complications following PD catheter implantation. DM, especially with HbA1C ≥7, significantly impacted on the catheter-related infection and the survival probability of the PD catheter.
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OBJECTIVE: Acute pancreatitis can usually recover after conservative treatment. Five to 10 percent of acute pancreatitis may proceed into peripancreatic fluid collection and necrosis development, called necrotizing pancreatitis (NP), which has a high mortality rate. If it is accompanied by the occurrence of abdominal compartment syndrome (ACS) and does not respond to medical therapy, surgical intervention is indicated. METHODS: We analyzed our experience of surgical intervention strategies for NP patients with medically irreversible ACS from January 1, 2004, to December 31, 2018. RESULTS: Of the 47 NP patients with ACS, mean Ranson score was 6.5, mean Acute Physiology and Chronic Health Evaluation II score was 22.2, and Modified computed tomography severity index score was all 8 or greater. The mean total postoperative hospital length of stay was 80.2 days, of which the mean intensive care unit length of stay was 16.6 days. The overall complication rate was 31.9%. The mortality rate was 8.5%. Among the 47 patients, only fungemia was significantly associated with mortality incidence. CONCLUSIONS: The combination of multiple drainage tube placement, feeding jejunostomy, and ileostomy at the same time were effective surgical intervention strategies for NP patients with ACS, which brought a lower mortality rate.
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Procedimentos Cirúrgicos do Sistema Digestório/métodos , Hipertensão Intra-Abdominal/cirurgia , Pancreatite Necrosante Aguda/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Hipertensão Intra-Abdominal/etiologia , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde/métodos , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Pancreatite Necrosante Aguda/complicações , Estudos RetrospectivosRESUMO
Calcitonin is a small peptide hormone secreted from the parafollicular cells of the thyroid gland in response to an increase in serum calcium. The inhibition of osteoclastic resorption is the main mechanism by which calcitonin quickly decreases circulating calcium levels. Although calcitonin pharmacologically acts on osteoclasts to prevent bone resorption, the results of studies on genetically modified animals have shown that the physiological effect of calcitonin is in the inhibition of osteoblastic bone formation. Because the calcitonin receptor is only expressed in osteoclasts, the effect of calcitonin on osteoblasts maybe indirect and mediated via osteoclasts. Wnt ligands are involved in various aspects of skeletal biology, including bone remodeling and endochondral bone formation. Wnt10b has recently been recognized as a clastokine, and is potentially a therapeutic target for treating bone disorders. However, the extent to which Wnt signaling is involved in bone physiology and disease is not yet fully understood. We hypothesize that calcitonin indirectly increases osteoblastic bone formation by inducing Wnt10b expression in osteoclasts. Micro-CT analysis revealed reduced bone loss in calcitonin-treated ovariectomized rats. The serum of animals treated with calcitonin had decreased TRAP5b and CTX-1 but increased osteocalcin, P1NP, and Wnt10b. Immunohistochemistry staining showed that the level of Wnt10b in the femur was increased in calcitonin-treated groups as compared with control groups. Hematopoietic mononuclear cells were separated from rat femur and tibia bone marrow, and were induced into osteoclasts following treatment with M-CSF and RANKL. In these cells, immunoconfocal microscopy and Western blot analysis showed that calcitonin induced an increase in Wnt10b expression. In a culture of osteoblasts isolated from neonatal rat calvariae, the calcitonin-treated osteoclast supernatant showed an increase in mineralization, as indicated by ALP and alizarin red staining. Taken together, these results indicate that calcitonin induces bone formation by increasing the expression of Wnt10b in osteoclasts in ovariectomy-induced osteoporotic rats. The present study provides in-depth information about the effects of calcitonin on bone remodeling and will thus help in the development of future potential therapeutic strategies for postmenopausal osteoporosis.
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Conservadores da Densidade Óssea/farmacologia , Calcitonina/farmacologia , Fêmur/efeitos dos fármacos , Osteoclastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteoporose/tratamento farmacológico , Osteoporose/metabolismo , Proteínas Wnt/metabolismo , Animais , Densidade Óssea/efeitos dos fármacos , Conservadores da Densidade Óssea/uso terapêutico , Remodelação Óssea/efeitos dos fármacos , Calcitonina/uso terapêutico , Feminino , Fêmur/diagnóstico por imagem , Fêmur/metabolismo , Osteoclastos/metabolismo , Osteoporose/diagnóstico por imagem , Osteoporose/etiologia , Ovariectomia/efeitos adversos , Ratos , Ratos Sprague-Dawley , Microtomografia por Raio-XRESUMO
BACKGROUND: Patients undergoing pancreaticoduodenectomy (PD) for periampullary lesions are usually elderly with a high risk of postoperative morbidity and mortality. This retrospective cohort study investigated whether postoperative preemptive light sedation aids in recovery of elderly patients following PD. METHODS: Ninety-nine geriatric patients undergoing PD at one hospital were enrolled from 2009 to 2018. Patients in the sedation group received mechanical ventilation support and preemptively light sedation with fentanyl and propofol or dexmedetomidine in the first 5 days postoperatively in the intensive care unit (ICU). Patients in the control group underwent early extubation and received morphine for pain control but no postoperative sedatives in the ordinary ward. Patients in the two groups were matched 1:1 using propensity scoring. The postoperative complication rate, surgical mortality, and postoperative hospital length of stay (LOS) were recorded. We also tested inflammation in an immortal human bronchial epithelial cell line. RESULTS: After 1:1 matching, 40 patients in the sedation group were compared with 40 patients in the control group. The sedation group had a significantly lower pulmonary complication rate and fewer patients with postoperative gastroparesis. Both groups had similar postoperative hospital LOS and identical surgical mortality rates. Patients in the sedation group had significantly better postoperative quality of life, including less pain and less heartbeat variation. In vitro cell experiments supported the above clinical observations, showing that adequate use of sedatives could significantly elevate the cell viability rate, protect cells from damage, decrease interleukin-6 production, and reduce inflammation. CONCLUSION: Postoperative preemptive light sedation in the ICU in geriatric patients following PD may not only reduce the rates of postoperative pulmonary complications and gastroparesis but also improve postoperative quality of life without prolonging the postoperative hospital LOS.
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Sedação Consciente , Pneumopatias/prevenção & controle , Pancreaticoduodenectomia/efeitos adversos , Complicações Pós-Operatórias/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Células Cultivadas , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: Despite the availability of current therapies, including oral antidiabetic drugs and insulin, for controlling the symptoms caused by high blood glucose, it is difficult to cure diabetes mellitus, especially type 1 diabetes mellitus. AIM: Cell therapies using mesenchymal stem cells (MSCs) may be a promising option. However, the therapeutic mechanisms by which MSCs exert their effects, such as whether they can differentiate into insulin-producing cells (IPCs) before transplantation, are uncertain. METHODS: In this study, we used three types of differentiation media over 10 d to generate IPCs from human Wharton's jelly MSCs (hWJ-MSCs). We further transplanted the undifferentiated hWJ-MSCs and differentiated IPCs derived from them into the portal vein of rats with streptozotocin-induced diabetes, and recorded the physiological and pathological changes. RESULTS: Using fluorescent staining and C-peptide enzyme-linked immunoassay, we were able to successfully induce the differentiation of hWJ-MSCs into IPCs. Transplantation of both IPCs derived from hWJ-MSCs and undifferentiated hWJ-MSCs had the therapeutic effect of ameliorating blood glucose levels and improving intraperitoneal glucose tolerance tests. The transplanted IPCs homed to the pancreas and functionally survived for at least 8 wk after transplantation, whereas the undifferentiated hWJ-MSCs were able to improve the insulitis and ameliorate the serum inflammatory cytokine in streptozotocin-induced diabetic rats. CONCLUSION: Differentiated IPCs can significantly improve blood glucose levels in diabetic rats due to the continuous secretion of insulin by transplanted cells that survive in the islets of diabetic rats. Transplantation of undifferentiated hWJ-MSCs can significantly improve insulitis and re-balance the inflammatory condition in diabetic rats with only a slight improvement in blood glucose levels.
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Pulmonary fibrosis (PF) is a progressive and irreversible condition with various causes, and no effective treatment has been found to rescue fibrotic lungs. Successful recovery from PF requires inhibiting inflammation, promoting collagen degradation and stimulating alveolar regeneration. Human umbilical mesenchymal stem cells (HUMSCs) not only regulate immune responses but also synthesize and release hyaluronan to improve lung regeneration. This study investigated the feasibility of HUMSC engraftment into rats with bleomycin (BLM)-induced PF to explore HUMSC therapeutic effects/outcomes. Methods: A unique BLM-induced left-lung-dominated PF animal model was established. Rats were transplanted with low-dose (5×106) or high-dose (2.5×107) HUMSCs on Day 21 after BLM injection. Combinations in co-culture of pulmonary macrophages, fibroblasts, HUMSCs treated with BLM and the same conditions on alveolar epithelia versus HUMSCs were evaluated. Results: Rats with high-dose HUMSC engraftment displayed significant recovery, including improved blood oxygen saturation levels and respiratory rates. High-dose HUMSC transplantation reversed alveolar injury, reduced cell infiltration and ameliorated collagen deposition. One month posttransplantation, HUMSCs in the rats' lungs remained viable and secreted cytokines without differentiating into alveolar or vascular epithelial cells. Moreover, HUMSCs decreased epithelial-mesenchymal transition in pulmonary inflammation, enhanced macrophage matrix-metallopeptidase-9 (MMP-9) expression for collagen degradation, and promoted toll-like receptor-4 (TLR-4) expression in the lung for alveolar regeneration. In coculture studies, HUMSCs elevated the MMP-9 level in pulmonary macrophages, released hyaluronan into the medium and stimulated the TLR-4 quantity in the alveolar epithelium. Principal Conclusions: Transplanted HUMSCs exhibit long-term viability in rat lungs and can effectively reverse rat PF.
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Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/metabolismo , Fibrose Pulmonar/terapia , Geleia de Wharton/citologia , Animais , Bleomicina/toxicidade , Diferenciação Celular , Citocinas/metabolismo , Modelos Animais de Doenças , Xenoenxertos , Humanos , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Células-Tronco Mesenquimais/citologia , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , Troca Gasosa Pulmonar , Ratos Sprague-Dawley , Testes de Função Respiratória , Receptor 4 Toll-Like/metabolismo , Transplante Heterólogo , Cordão Umbilical/citologiaRESUMO
BACKGROUND: Spinocerebellar ataxia type 1 (SCA1) is an autosomal dominant neurodegenerative disorder caused by the expansion of CAG repeats in ATXN1 gene resulting in an expansion of polyglutamine repeats in the ATXN1 protein. Unfortunately, there has yet been any effective treatment so far for SCA1. This study investigated the feasibility of transplanting human umbilical mesenchymal stem cells (HUMSCs) into transgenic SCA1 mice containing an expanded uninterrupted allele with 82 repeats in the ATXN1-coding region. METHODS: 106 human umbilical mesenchymal stem cells were transplanted into the cerebella at 1 month of age. RESULTS: HUMSCs displayed significant ameliorating effects in SCA1 mice in terms of motor behaviors in balance beam test and open field test as compared with the untransplanted SCA1 mice. HUMSCs transplantation effectively reduced the cerebellar atrophy, salvaged Purkinje cell death, and alleviated molecular layer shrinkage. Electrophysiological studies showed higher amplitudes of compound motor action potentials as indicated by increasing neuronal-muscular response strength to stimuli after stem cell transplantation. At 5 months after transplantation, HUMSCs scattering in the mice cerebella remained viable and secreted cytokines without differentiating into neuronal or glia cells. CONCLUSIONS: Our findings provide hope for a new therapeutic direction for the treatment of SCA1.
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Mesenchymal stem cells (MSCs) are known for homing to sites of injury in response to signals of cellular damage. However, the mechanisms of how cytokines recruit stem cells to target tissue are still unclear. In this study, we found that the proinflammation cytokine interleukin-1ß (IL-1ß) promotes mesenchymal stem cell migration. The cDNA microarray data show that IL-1ß induces matrix metalloproteinase-1 (MMP-1) expression. We then used quantitative real-time PCR and MMP-1 ELISA to verify the results. MMP-1 siRNA transfected MSCs, and MSC pretreatment with IL-1ß inhibitor interleukin-1 receptor antagonist (IL-1RA), MMP tissue inhibitor of metalloproteinase 1 (TIMP1), tissue inhibitor of metalloproteinase 2 (TIMP2), MMP-1 inhibitor GM6001, and protease-activated receptor 1 (PAR1) inhibitor SCH79797 confirms that PAR1 protein signaling pathway leads to IL-1ß-induced cell migration. In conclusion, IL-1ß promotes the secretion of MMP-1, which then activates the PAR1 and G-protein-coupled signal pathways to promote mesenchymal stem cell migration.
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BACKGROUND: Gallstone disease is one of the leading upper gastrointestinal surgical problems in different countries. AIMS: To analyze the chronic gallstones and acute gallbladder sludge retrieved from 36 Taiwanese patients. METHODS: FTIR microspectroscopy was used to classify the types of gallstones, and an ESEM-EDX microanalysis was first applied to determine the microstructural features and elemental compositions of the various gallstones. Bacteria presented on the surface of gallstones were also detected by SEM. RESULTS: Four types of gallstones were obtained from these 36 Taiwanese patients: calcium bilirubinate (CaBR) stones (30.6%), cholesterol stones (19.4%), mixed stones including 6 subtypes (47.2%), and acute gallbladder sludge (2.8%) made of CaBR and protein/insoluble biomaterials. Bacteria imprints and bacterial discharges or bacterial biofilms were also found on the surface of gallstones and acute sludge under a SEM observation. ESEM-EDX results revealed that calcium was found to be the main constituent of all of the types of stones except cholesterol stones, and aluminum was also presented in most of the stones and sludge samples. Chloride was only detected in the acute gallbladder sludge. CONCLUSION: FTIR spectra, morphological features, and elemental compositions of the acute gallbladder sludge were different from those of the chronic gallstones.
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Bile/química , Bilirrubina/análise , Colesterol/análise , Cálculos Biliares/química , Cálculos Biliares/classificação , Doença Aguda , Adulto , Idoso , Alumínio/análise , Bile/microbiologia , Cálcio/análise , Cloretos/análise , Doença Crônica , Durapatita/análise , Microanálise por Sonda Eletrônica , Feminino , Cálculos Biliares/microbiologia , Humanos , Masculino , Microscopia Eletrônica de Varredura/métodos , Pessoa de Meia-Idade , Espectroscopia de Infravermelho com Transformada de Fourier , Ácidos Esteáricos/análise , TaiwanRESUMO
Background. Type 1 diabetes mellitus results from autoimmune destruction of ß-cells. Insulin-producing cells (IPCs) differentiated from mesenchymal stem cells (MSCs) in human tissues decrease blood glucose levels and improve survival in diabetic rats. We compared the differential ability and the curative effect of IPCs from three types of human tissue to determine the ideal source of cell therapy for diabetes. Methods. We induced MSCs from Wharton's jelly (WJ), bone marrow (BM), and surgically resected pancreatic tissue to differentiate into IPCs. The in vitro differential function of these IPCs was compared by insulin-to-DNA ratios and C-peptide levels after glucose challenge. In vivo curative effects of IPCs transplanted into diabetic rats were monitored by weekly blood glucose measurement. Results. WJ-MSCs showed better proliferation and differentiation potential than pancreatic MSCs and BM-MSCs. In vivo, WJ-IPCs significantly reduced blood glucose levels at first week after transplantation and maintained significant decrease till week 8. BM-IPCs reduced blood glucose levels at first week but gradually increased since week 3. In resected pancreas-IPCs group, blood glucose levels were significantly reduced till two weeks after transplantation and gradually increased since week 4. Conclusion. WJ-MSCs are the most promising stem cell source for ß-cell regeneration in diabetes treatment.
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Type 1 diabetes mellitus is caused by T-cell-mediated autoimmune destruction of pancreatic ß-cells. Systemic administration of mesenchymal stem cells (MSCs) brings about their incorporation into a variety of tissues with immunosuppressive effects, resulting in regeneration of pancreatic islets. We previously showed that human MSCs isolated from Wharton's jelly (WJ-MSCs) represent a potential cell source to treat diabetes. However, the underlying mechanisms are unclear. The purpose of this study was to discern whether undifferentiated WJ-MSCs can differentiate into pancreatic insulin-producing cells (IPCs) and modify immunological responses in nonobese diabetic (NOD) mice. Undifferentiated WJ-MSCs underwent lentiviral transduction to express green fluorescent protein (GFP) and then were injected into the retro-orbital venous sinus of NOD mice. Seven days after transplantation, fluorescent islet-like cell clusters in the pancreas were apparent. WJ-MSC-GFP-treated NOD mice had significantly lower blood glucose and higher survival rates than saline-treated mice. Systemic and local levels of autoaggressive T-cells, including T helper 1 cells and IL-17-producing T-cells, were reduced, and regulatory T-cell levels were increased. Furthermore, anti-inflammatory cytokine levels were increased, and dendritic cells were decreased. At 23 days, higher human C-peptide and serum insulin levels and improved glucose tolerance were found. Additionally, WJ-MSCs-GFP differentiated into IPCs as shown by colocalization of human C-peptide and GFP in the pancreas. Significantly more intact islets and less severe insulitis were observed. In conclusion, undifferentiated WJ-MSCs can differentiate into IPCs in vivo with immunomodulatory effects and repair the destroyed islets in NOD mice.
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Diabetes Mellitus Experimental/terapia , Células Secretoras de Insulina/citologia , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Linfócitos T/imunologia , Geleia de Wharton/citologia , Animais , Autoimunidade , Glicemia/análise , Peptídeo C/sangue , Diferenciação Celular , Células Cultivadas , Citocinas/genética , Citocinas/metabolismo , Diabetes Mellitus Experimental/mortalidade , Diabetes Mellitus Experimental/patologia , Feminino , Humanos , Insulina/sangue , Células Secretoras de Insulina/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos NOD , Taxa de Sobrevida , Linfócitos T/citologia , Linfócitos T/metabolismoRESUMO
Mesenchymal stem cells (MSCs) migrate via the bloodstream to sites of injury, possibly attracted by inflammatory cytokines. Although many cytokines can induce stem cell migration, the underlying mechanism is not fully understood. We found that tail vein-injected MSCs migrate to the pancreas in nonobese diabetic (NOD) mice. An ELISA assay revealed that hyperglycemic NOD mice have higher pancreatic levels of interleukin-1ß (IL-1ß) than normal NOD mice and that IL-1ß stimulates MSC migration in a Transwell assay and electric cell-substrate impedance sensing system. Microarray analysis showed that myosin light chain kinase (MLCK) is involved in IL-1ß-induced MSC migration, while Western blots showed that IL-1ß stimulates MLCK expression and activation and that MLCK-siRNA transfection reduces MSC migration. Kinase inhibitors, chromatin immunoprecipitation, and a knockdown study revealed that IL-1ß-induced MLCK expression is regulated by the PKCδ/NF-κB signaling pathway, and a kinase inhibitor study revealed that IL-1ß-induced MLCK activation occurs via the PKCα/MEK/ERK signaling pathway. These results show that IL-1ß released from the pancreas of hyperglycemic NOD mice induces MSC migration and that this is dependent on MLCK expression via the PKCδ/NF-κB pathway and on MLCK activation via the PKCα/MEK/ERK signaling cascade. This study increases our understanding of the mechanisms by which MSCs home to injury sites.
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Movimento Celular/efeitos dos fármacos , Interleucina-1beta/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Quinase de Cadeia Leve de Miosina/metabolismo , Proteína Quinase C/metabolismo , Transdução de Sinais/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Feminino , Interleucina-1beta/metabolismo , Células-Tronco Mesenquimais/citologia , Camundongos , RNA Interferente Pequeno/genéticaAssuntos
Hérnia do Obturador/etiologia , Hérnia do Obturador/cirurgia , Falência Renal Crônica/terapia , Diálise Peritoneal Ambulatorial Contínua/efeitos adversos , Feminino , Seguimentos , Hérnia do Obturador/fisiopatologia , Herniorrafia/métodos , Humanos , Falência Renal Crônica/diagnóstico , Pessoa de Meia-Idade , Diálise Peritoneal Ambulatorial Contínua/métodos , Doenças Raras , Medição de Risco , Índice de Gravidade de Doença , Resultado do TratamentoRESUMO
We studied the process of trans-differentiation of human bone marrow mesenchymal stem cells (hBM-MSCs) into insulin-producing cells. Streptozotocin (STZ)-induced diabetic rat model was used to study the effect of portal vein transplantation of these insulin-producing cells on blood sugar levels. The BM-MSCs were differentiated into insulin-producing cells under defined conditions. Real-time PCR, immunocytochemistry and glucose challenge were used to evaluate in vitro differentiation. Flow cytometry showed that hBM-MSCs were strongly positive for CD44, CD105 and CD73 and negative for hematopoietic markers CD34, CD38 and CD45. Differentiated cells expressed C-peptide as well as ß-cells specific genes and hormones. Glucose stimulation increased C-peptide secretion in these cells. The insulin-producing, differentiated cells were transplanted into the portal vein of STZ-induced diabetic rats using a Port-A catheter. The insulin-producing cells were localized in the liver of the recipient rat and expressed human C-peptide. Blood glucose levels were reduced in diabetic rats transplanted with insulin-producing cells. We concluded that hBM-MSCs could be trans-differentiated into insulin-producing cells in vitro. Portal vein transplantation of insulin-producing cells alleviated hyperglycemia in diabetic rats.
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Glicemia , Células da Medula Óssea , Diabetes Mellitus Experimental/terapia , Células Secretoras de Insulina/transplante , Células-Tronco Mesenquimais , Animais , Diferenciação Celular , Diabetes Mellitus Experimental/sangue , Humanos , Insulina/metabolismo , Secreção de Insulina , Masculino , Ratos , Ratos Sprague-Dawley , Resultado do TratamentoRESUMO
BACKGROUND/AIMS: Periampullary lesions often present diagnostic and therapeutic dilemmas. This study is to clarify the justification of pancreaticoduodenectomy for the resectable periampullary lesion without histological confirmation of malignancy. METHODOLOGY: Clinical data for periampullary lesions with presumed malignancy were retrieved from our prospectively-collected computer database. The surgical risks and test performance characteristics in diagnosis were determined. RESULTS: There were 636 patients undergoing pancreaticoduodenectomy, including 572 with malignancy and 64 (10.1% false positive rate) with benign lesions. No resection was attempted for 32 patients, but 8 (25% false negative rate) eventually turned out to be malignant. Our data showed a sensitivity of 98.6% (572/580), a specificity of 27% (24/88) and an accuracy of 89.2% (596/668) in detecting periampullary malignancy. The surgical risks after pancreaticoduodenectomy were significantly lower in the benign group, with 28.1% morbidity (vs. 43.7% in the malignant group), no pancreatic leakage (vs. 11.5% in malignant group) and no surgical mortality (vs. 7.3% in the malignant group). CONCLUSIONS: Pancreaticoduodenectomy is justified for a periampullary lesion without histological confirmation whenever malignancy is suspected. Moreover, a nihilistic approach could be associated with a significant false negative rate (25%) if left unresected and might preclude a patient with periampullary malignancy from cure.
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Ampola Hepatopancreática/patologia , Neoplasias do Ducto Colédoco/patologia , Neoplasias Duodenais/patologia , Neoplasias Pancreáticas/patologia , Pancreaticoduodenectomia , Dor Abdominal/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ampola Hepatopancreática/cirurgia , Biópsia , Distribuição de Qui-Quadrado , Neoplasias do Ducto Colédoco/complicações , Neoplasias do Ducto Colédoco/cirurgia , Neoplasias Duodenais/complicações , Neoplasias Duodenais/cirurgia , Reações Falso-Negativas , Reações Falso-Positivas , Feminino , Humanos , Icterícia/etiologia , Masculino , Pessoa de Meia-Idade , Neoplasias Pancreáticas/complicações , Neoplasias Pancreáticas/cirurgia , Pancreaticoduodenectomia/efeitos adversos , Pancreatite Crônica/complicações , Pancreatite Crônica/patologia , Pancreatite Crônica/cirurgia , Valor Preditivo dos Testes , Estatísticas não Paramétricas , Redução de Peso , Adulto JovemRESUMO
BACKGROUND: Although diabetes mellitus (DM) can be treated with islet transplantation, a scarcity of donors limits the utility of this technique. This study investigated whether human mesenchymal stem cells (MSCs) from umbilical cord could be induced efficiently to differentiate into insulin-producing cells. Secondly, we evaluated the effect of portal vein transplantation of these differentiated cells in the treatment of streptozotocin-induced diabetes in rats. METHODS: MSCs from human umbilical cord were induced in three stages to differentiate into insulin-producing cells and evaluated by immunocytochemistry, reverse transcriptase, and real-time PCR, and ELISA. Differentiated cells were transplanted into the liver of diabetic rats using a Port-A catheter via the portal vein. Blood glucose levels were monitored weekly. RESULTS: Human nuclei and C-peptide were detected in the rat liver by immunohistochemistry. Pancreatic ß-cell development-related genes were expressed in the differentiated cells. C-peptide release was increased after glucose challenge in vitro. Furthermore, after transplantation of differentiated cells into the diabetic rats, blood sugar level decreased. Insulin-producing cells containing human C-peptide and human nuclei were located in the liver. CONCLUSION: Thus, a Port-A catheter can be used to transplant differentiated insulin-producing cells from human MSCs into the portal vein to alleviate hyperglycemia among diabetic rats.
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Diabetes Mellitus Experimental/tratamento farmacológico , Insulina , Fígado/metabolismo , Transplante de Células-Tronco Mesenquimais , Animais , Glicemia/análise , Peptídeo C , Diferenciação Celular , Humanos , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Fígado/citologia , Células-Tronco Mesenquimais/citologia , Veia Porta , Ratos , Cordão Umbilical/citologiaRESUMO
Neurofibromas arise from peripheral nerve cells. They are rarely found within the pancreas, especially not associated with type I neurofibromatosis. Here, we report a case of a neurofibroma in a 44-year-old woman who initially presented with epigastralgia. Imaging revealed one large cystic mass of 5.7 × 8 × 5.8 cm in the pancreatic body, which was resected with distal pancreatectomy. The postoperative course of treatment was without complication, and no signs of recurrence were observed after 1 year and 6 months' follow-up.
Assuntos
Neurofibroma/patologia , Neurofibromatose 1/patologia , Neoplasias Pancreáticas/patologia , Adulto , Feminino , Humanos , Neurofibroma/cirurgia , Neoplasias Pancreáticas/cirurgiaRESUMO
Infectious complications are the top causes of morbidity and mortality in patients who undergo renal transplantation. We report a patient who received a cadaveric renal transplant in Mainland China. One year post-transplantation, the patient had right buttock pain with radiation to the leg. Swelling and tenderness over the right groin was also found. Magnetic resonance imaging revealed a multilobulated cystic lesion, about 8 x 7 cm, at the right iliac fossa and presacral region extending to the posterior aspect of the graft kidney and up to the right psoas muscle. Drainage of the intra-abdominal abscess was performed. The abscess culture showed presence of Aspergillus spp. The patient had received steroids, tacrolimus and mycophenolate mofetil, which could be a risk factor for fungal infection. The cause of Aspergillus infection in our patient remains unclear. It may have been due to immune system insufficiency of the patient rendering the patient prone to infection. Pseudoaneurysm formation of the internal iliac artery following Aspergillus infection after kidney transplantation is rarely reported. Although it is a dilemma, once a severe situation such as pseudoaneurysm with aspergillosis presents, graft removal is suggested.