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1.
World J Clin Cases ; 12(12): 2122-2127, 2024 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-38680266

RESUMO

BACKGROUND: Crossed renal ectopia (CRE) occurs when one kidney crosses the midline from the primary side to the contralateral side while the ureter remains on the primary side. Rectal cancer, one of the most common malignant tumors of the digestive tract, refers to cancer from the dentate line to the rectosigmoid junction. The concurrent presentation of CRE alongside rectal cancer is an uncommon clinical observation. CASE SUMMARY: Herein, we report a 69-year-old male patient with rectal cancer who was diagnosed with CRE via computed tomography during hospitalization. Following thorough preoperative evaluations, the patient underwent Dixon surgery. CONCLUSION: We performed laparoscopic radical resection of rectal cancer and adequate lymph node removal in a patient with CRE with no postoperative discomfort.

2.
Adv Healthc Mater ; 12(28): e2301316, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37531238

RESUMO

Critical limb ischemia, the final course of peripheral artery disease, is characterized by an insufficient supply of blood flow and excessive oxidative stress. H2 S molecular therapy possesses huge potential for accelerating revascularization and scavenging intracellular reactive oxygen species (ROS). Moreover, it is found that BMP6 is the most significantly up-expressed secreted protein-related gene in HUVECs treated with GYY4137, a H2 S donor, based on the transcriptome analysis. Herein, a UIO-66-NH2 @GYY4137@BMP6 co-delivery nanoplatform to strengthen the therapeutic effects of limb ischemia is developed. The established UIO-66-NH2 @GYY4137@BMP6 nanoplatform exerts its proangiogenic and anti-oxidation functions by regulating key pathways. The underlying molecular mechanisms of UIO-66-NH2 @GYY4137@BMP6 dual-loading system lie in the upregulation of phosphorylated YAP/TAZ and Jun to promote HUVECs proliferation and downregulation of phosphorylated p53/p21 to scavenge excessive ROS. Meanwhile, laser-doppler perfusion imaging (LDPI), injury severity evaluation, and histological analysis confirm the excellent therapeutic effects of UIO-66-NH2 @GYY4137@BMP6 in vivo. This work may shed light on the treatment of critical limb ischemia by regulating YAP, Jun, and p53 signaling pathways based on gas-protein synergistic therapy.


Assuntos
Isquemia Crônica Crítica de Membro , Proteína Supressora de Tumor p53 , Humanos , Proteína Supressora de Tumor p53/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteína Morfogenética Óssea 6/metabolismo
3.
BMJ Open ; 13(4): e066782, 2023 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-37012019

RESUMO

OBJECTIVES: To conduct a comprehensive analysis of demographic information, medical history, and blood pressure (BP) and heart rate (HR) variability during hospitalisation so as to establish a predictive model for preoperative in-hospital mortality of patients with acute aortic dissection (AD) by using machine learning techniques. DESIGN: Retrospective cohort study. SETTING: Data were collected from the electronic records and the databases of Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine and the First Affiliated Hospital of Anhui Medical University between 2004 and 2018. PARTICIPANTS: 380 inpatients diagnosed with acute AD were included in the study. PRIMARY OUTCOME: Preoperative in-hospital mortality rate. RESULTS: A total of 55 patients (14.47%) died in the hospital before surgery. The results of the areas under the receiver operating characteristic curves, decision curve analysis and calibration curves indicated that the eXtreme Gradient Boosting (XGBoost) model had the highest accuracy and robustness. According to the SHapley Additive exPlanations analysis of the XGBoost model, Stanford type A, maximum aortic diameter >5.5 cm, high variability in HR, high variability in diastolic BP and involvement of the aortic arch had the greatest impact on the occurrence of in-hospital deaths before surgery. Moreover, the predictive model can accurately predict the preoperative in-hospital mortality rate at the individual level. CONCLUSION: In the current study, we successfully constructed machine learning models to predict the preoperative in-hospital mortality of patients with acute AD, which can help identify high-risk patients and optimise the clinical decision-making. Further applications in clinical practice require the validation of these models using a large-sample, prospective database. TRIAL REGISTRATION NUMBER: ChiCTR1900025818.


Assuntos
Dissecção Aórtica , Pacientes Internados , Humanos , Mortalidade Hospitalar , Estudos Retrospectivos , China , Dissecção Aórtica/cirurgia , Aprendizado de Máquina
4.
J Vasc Surg Venous Lymphat Disord ; 11(3): 555-564.e5, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36580997

RESUMO

BACKGROUND: Post-thrombotic syndrome (PTS) is the most common chronic complication of deep venous thrombosis (DVT). Risk measurement and stratification of PTS are crucial for patients with DVT. This study aimed to develop predictive models of PTS using machine learning for patients with proximal DVT. METHODS: Herein, hospital inpatients from a DVT registry electronic health record database were randomly divided into a derivation and a validation set, and four predictive models were constructed using logistic regression, simple decision tree, eXtreme Gradient Boosting (XGBoost), and random forest (RF) algorithms. The presence of PTS was defined according to the Villalta scale. The areas under the receiver operating characteristic curves, decision-curve analysis, and calibration curves were applied to evaluate the performance of these models. The Shapley Additive exPlanations analysis was performed to explain the predictive models. RESULTS: Among the 300 patients, 126 developed a PTS at 6 months after DVT. The RF model exhibited the best performance among the four models, with an area under the receiver operating characteristic curves of 0.891. The RF model demonstrated that Villalta score at admission, age, body mass index, and pain on calf compression were significant predictors for PTS, with accurate prediction at the individual level. The Shapley Additive exPlanations analysis suggested a nonlinear correlation between age and PTS, with two peak ages of onset at 50 and 70 years. CONCLUSIONS: The current predictive model identified significant predictors and accurately predicted PTS for patients with proximal DVT. Moreover, the model demonstrated a nonlinear correlation between age and PTS, which might be valuable in risk measurement and stratification of PTS in patients with proximal DVT.


Assuntos
Síndrome Pós-Flebítica , Síndrome Pós-Trombótica , Trombose Venosa , Humanos , Pessoa de Meia-Idade , Idoso , Trombose Venosa/diagnóstico , Trombose Venosa/diagnóstico por imagem , Fatores de Risco , Síndrome Pós-Trombótica/etiologia , Síndrome Pós-Trombótica/complicações , Síndrome Pós-Flebítica/etiologia , Bases de Dados Factuais
5.
Br J Cancer ; 128(2): 219-231, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36347964

RESUMO

BACKGROUND: Hand-foot syndrome (HFS) is a serious dose-limiting cutaneous toxicity of capecitabine-containing chemotherapy, leading to a deteriorated quality of life and negative impacts on chemotherapy treatment. The symptoms of HFS have been widely reported, but the precise molecular and cellular mechanisms remain unknown. The metabolic enzyme of capecitabine, thymidine phosphorylase (TP) may be related to HFS. Here, we investigated whether TP contributes to the HFS and the molecular basis of cellular toxicity of capecitabine. METHODS: TP-/- mice were generated to assess the relevance of TP and HFS. Cellular toxicity and signalling mechanisms were assessed by in vitro and in vivo experiments. RESULTS: TP-/- significantly reduced capecitabine-induced HFS, indicating that the activity of TP plays a critical role in the development of HFS. Further investigations into the cellular mechanisms revealed that the cytotoxicity of the active metabolite of capecitabine, 5-DFUR, was attributed to the cleavage of GSDME-mediated pyroptosis. Finally, we demonstrated that capecitabine-induced HFS could be reversed by local application of the TP inhibitor tipiracil. CONCLUSION: Our findings reveal that the presence of elevated TP expression in the palm and sole aggravates local cell cytotoxicity, further explaining the molecular basis underlying 5-DFUR-induced cellular toxicity and providing a promising approach to the therapeutic management of HFS.


Assuntos
Fluoruracila , Síndrome Mão-Pé , Animais , Camundongos , Capecitabina/farmacologia , Fluoruracila/farmacologia , Síndrome Mão-Pé/tratamento farmacológico , Síndrome Mão-Pé/etiologia , Piroptose , Timidina Fosforilase/genética , Timidina Fosforilase/metabolismo , Qualidade de Vida , Desoxicitidina/efeitos adversos
6.
Stem Cell Res Ther ; 13(1): 349, 2022 07 26.
Artigo em Inglês | MEDLINE | ID: mdl-35883151

RESUMO

BACKGROUND: Preclinical studies have suggested that adipose-derived mesenchymal stem cells (ADSCs) transplantation can suppress abdominal aortic inflammation and aneurysm expansion through paracrine factors. Yet, the mechanism of action is not fully understood. In the present study, we further examined the function and mechanism of ADSC-derived exosomes (ADSC-exos) and their microRNA-17-5p (miR-17-5p) on the abdominal aortic aneurysm (AAA) progression. METHODS: ADSC-exos were isolated and identified. DiR and PKH67 staining were used to trace ADSC-exo in vivo and in vitro. Raw264.7 cells were applied to perform in vitro experiments, while a murine AAA model induced using angiotensin II (Ang II) was used for in vivo testing. The expression level of miR-17-5p in macrophages and Ang II-treated macrophages after ADSC-exos treatment was determined using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The target relation between miR-17-5p and thioredoxin-interacting protein (TXNIP) was identified by a dual-luciferase reporter gene assay. Artificial activation and block of experiments of miR-17-5p and TXNIP were conducted to clarify their functions in inflammation during AAA progression. The severity of AAA between groups was assessed by maximal aorta diameter, AAA incidence, survival rate, and histological stainings. Besides, inflammasome-related proteins and macrophage pyroptosis were further evaluated using western blot, RT-qPCR, and enzyme-linked immunosorbent assay (ELISA). RESULTS: The ADSC-exos were isolated and identified. In vivo testing showed that ADSC-exos were mainly distributed in the liver. Meanwhile, in vitro experiments suggested that ADSC-derived exosomes were taken up by macrophages, while inside, ADSC-exos miR-17-5p decreased a TXNIP induced by Ang II by directly binding to its 3'-untranslated region (3'UTR). Furthermore, overexpression of miR-17-5p enhanced the therapeutic function of ADSC-exos on inflammation during AAA expansion in vivo, while its inhibition reversed this process. Finally, overexpressed TXNIP triggered macrophage pyroptosis and was alleviated by ADSC-derived exosomes in vitro. CONCLUSION: ADSC-exos miR-17-5p regulated AAA progression and inflammation via the TXNIP-NLRP3 signaling pathway, thus providing a novel insight in AAA treatment.


Assuntos
Aneurisma da Aorta Abdominal , Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Animais , Aneurisma da Aorta Abdominal/genética , Aneurisma da Aorta Abdominal/metabolismo , Aneurisma da Aorta Abdominal/terapia , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Exossomos/genética , Exossomos/metabolismo , Inflamassomos/genética , Inflamação/genética , Inflamação/metabolismo , Inflamação/terapia , Células-Tronco Mesenquimais/metabolismo , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Tiorredoxinas/genética
7.
J Invest Dermatol ; 142(11): 3052-3061.e8, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35618045

RESUMO

EGF receptor (EGFR) inhibitors have been established as first-line standard-of-care therapies for nonsmall cell lung cancer but are frequently accompanied by adverse dermatological effects, in particular, acneiform rash. There is no effective clinical intervention, partially because of its poorly understood etiology. In this study, we show that inhibition of EGFR initiated keratinocyte HaCaT cell cycle arrest and apoptosis, which fueled a robust secondary inflammatory response. Rats gavaged with EGFR inhibitor showed a phenotype similar to that of clinical patients, which was in line with the interrupted functions observed in HaCaT keratinocytes. We found that a nitric oxide donor, nitroglycerin, was a feasible treatment alternative for EGFR inhibitor‒induced rash. Restoration of epidermal extracellular signal‒regulated kinase and a reduction in signal transducer and activator of transcription 3 signaling through nitroglycerin treatment rescued the cellular functions that had been damaged in vitro and further ameliorated the rash in rat models. In addition, the efficacy of nitroglycerin was superior to that of existing clinical interventions. These data highlighted the importance of epidermal EGFR signaling and led to the identification of a small-molecule nitric oxide donor as a mediator that can maintain EGFR pathway functions during anti-EGFR therapies, providing a therapeutic anchor point for adverse EGFRI-induced skin effects.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Exantema , Neoplasias Pulmonares , Dermatopatias , Ratos , Animais , Doadores de Óxido Nítrico/farmacologia , Doadores de Óxido Nítrico/uso terapêutico , Fator de Transcrição STAT3/metabolismo , Nitroglicerina/farmacologia , Receptores ErbB/metabolismo , Inibidores de Proteínas Quinases/farmacologia , MAP Quinases Reguladas por Sinal Extracelular/metabolismo
8.
Nutrients ; 14(5)2022 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-35267945

RESUMO

Liver injury is a life-threatening condition that is usually caused by excessive alcohol consumption, improperdiet, and stressful lifestyle and can even progress to liver cancer. Tea is a popular beverage with proven health benefits and is known to exert a protective effect on the liver, intestines, and stomach. In this study, we analyzed the therapeutic effects of six kinds of tea on carbon tetrachloride (CCl4)-induced liver injury in a mouse model. The mice were injected with 10 mL/kg 5% CCl4 to induce liver injury and then given oral gavage of green tea, yellow tea, oolong tea, white tea, black tea, and dark tea, respectively. The serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were measured, and the expression levels of inflammation and oxidative stress-related proteins in the liver tissues were quantified. All six kinds of tea partly reduced the liver index, restored the size of the enlarged liver in the CCl4 model, and decreased the serum levels of ALT and AST. Furthermore, the highly fermented dark tea significantly reduced the expression levels of NF-κB and the downstream inflammatory factors, whereas the unfermented green tea inhibited oxidative stress by activating the antioxidant Nrf2 pathway. Taken together, tea can protect against liver inflammation, and unfermented tea can improve antioxidant levels. Further studies are needed on the bioactive components of tea to develop drugs against liver injury.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Animais , China , Camundongos , Camundongos Endogâmicos C57BL , Chá
9.
Elife ; 112022 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-35324426

RESUMO

Anti-epidermal growth factor receptor (EGFR) therapy-associated cutaneous toxicity is a syndrome characterized by papulopustular rash, local inflammation, folliculitis, and microbial infection, resulting in a decrease in quality of life and dose interruption. However, no effective clinical intervention is available for this adverse effect. Here, we report the atrophy of dermal white adipose tissue (dWAT), a highly plastic adipose tissue with various skin-specific functions, correlates with rash occurrence and exacerbation in a murine model of EGFR inhibitor-induced rash. The reduction in dWAT is due to the inhibition of adipogenic differentiation by defects in peroxisome proliferator-activated receptor γ (PPARγ) signaling, and increased lipolysis by the induced expression of the lipolytic cytokine IL6. The activation of PPARγ by rosiglitazone maintains adipogenic differentiation and represses the transcription of IL6, eventually improving skin functions and ameliorating the severity of rash without altering the antitumor effects. Thus, activation of PPARγ represents a promising approach to ameliorate cutaneous toxicity in patients with cancer who receive anti-EGFR therapy.


Assuntos
Exantema , PPAR gama , Tecido Adiposo/metabolismo , Animais , Receptores ErbB , Humanos , Interleucina-6/genética , Camundongos , PPAR gama/metabolismo , Qualidade de Vida
10.
Head Neck ; 44(6): 1414-1421, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35319144

RESUMO

BACKGROUND: To assess the efficacy and safety of preoperative embolization (PE) in patients with carotid body tumor (CBTs). METHODS: In a single-center retrospective cohort study, 127 patients underwent surgical resection of CBTs from January 2003 to December 2019. One-to-one propensity score matching was conducted between patients with or without PE. RESULTS: Thirty-two (25.2%) patients received PE. After propensity score matching, no statistically significant differences were found in the baseline characteristics of 28 patients in each group. Compared with NPE group, operative time and estimated blood loss (EBL) were significantly reduced in the PE group. The incidence of stroke, perioperative complications, intraoperative blood transfusion, vascular reconstruction, hospital stay, tumor recurrence, and all-cause mortality were not different between the PE and NPE group. CONCLUSIONS: Preoperative embolization was efficient and safe with a reduction of intraoperative blood loss and operative time during CBT resection.


Assuntos
Tumor do Corpo Carotídeo , Embolização Terapêutica , Tumor do Corpo Carotídeo/patologia , Tumor do Corpo Carotídeo/cirurgia , Humanos , Recidiva Local de Neoplasia , Pontuação de Propensão , Estudos Retrospectivos , Resultado do Tratamento
11.
Transl Res ; 245: 82-98, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35189405

RESUMO

Hand-foot skin reaction (HFSR) is the most debilitating and prevalent side effect caused by multikinase inhibitors (MKIs) that share vascular endothelial growth factor receptor (VEGFR) as the common inhibition target, such as sorafenib, regorafenib, axitinib, etc. Though not life-threatening, HFSR can significantly deteriorate patients' quality of life and jeopardize the continuity of cancer therapy. Despite years of efforts, there are no FDA-approved treatments for HFSR and the understanding of the precise pathogenic mechanism is still limited. In this study, we hypothesized that nitric oxide has the potential therapeutic effect to reverse the toxicity caused by MKI through upregulation of several VEGF/VEGFR downstream signaling pathways. We found that glyceryl trinitrate (GTN), a nitric oxide donor, could stimulate cell proliferation, migration, and protect cells from apoptosis induced by MKIs in vitro. Local application of GTN mitigated tissue damage in a rat model, while not impacting the anti-tumor effect of the MKI in HepG2 tumor-bearing mice. Finally, GTN ointment alleviated cutaneous damages and improved quality of life in 6 HFSR patients. Our study proposed and validated the mechanism to counteract VEGFR inhibition, providing GTN as the potential treatment to MKI-induced HFSR, which may further improve the therapeutic window of various MKI based cancer therapies.


Assuntos
Óxido Nítrico , Inibidores de Proteínas Quinases , Animais , Humanos , Camundongos , Inibidores de Proteínas Quinases/farmacologia , Qualidade de Vida , Ratos , Sorafenibe , Fator A de Crescimento do Endotélio Vascular
12.
J Vasc Surg ; 75(1): 356-362.e4, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34197945

RESUMO

OBJECTIVE: The necessity and efficacy of statin treatment for abdominal aortic aneurysm (AAA) remains controversial. This systematic review and meta-analysis was conducted to investigate the effects of statin therapy on the outcomes of patients with AAA. METHODS: The Cochrane library, Embase, and MedLine were searched comprehensively to identify relevant cohort studies and randomized controlled trials. The primary outcomes included short- and long-term mortality after AAA repair, and secondary outcomes included the incidence of perioperative cardiovascular complications, sac shrinkage after endovascular aneurysm repair, and the growth rate of the aneurysms. Short-term mortality was defined as all-cause 30-day or in-hospital postoperative mortality. Long-term mortality was defined as the all-cause mortality at the end of follow-up period (≥1 year). A random effects model was used to combine the results of included studies. Forest plots were created to show the pooled results of each outcome. RESULTS: One post hoc analysis of a randomized trial and 36 cohort studies (n = 134,290 patients) were included in this systematic review. The average score of included studies by Newcastle-Ottawa Scale was 7.76. Patients taking or not taking statin therapy were all diagnosed with unruptured AAA, and 59.9% of these patients were given statin therapy. Compared with statin nonusers, patients in statin therapy had significantly lower long-term mortality (odds ratio, 0.67; 95% confidence interval, 0.59-0.75; P < .001; I2 = 71.7%), and short-term mortality after aneurysmal repair (odds ratio, 0.51; 95% confidence interval, 0.36-0.73; P < .001; I2 = 81.4%). No significant difference was found between patients taking or not taking statin treatment on perioperative cardiovascular complications or sac shrinkage after endovascular aneurysm repair or growth rate of AAA under surveillance. CONCLUSIONS: These findings suggest that statin use is associated with a significant decrease in long- and short-term mortality in patients after AAA repair. Based on these results, statin therapy is worth being used in clinical practice for the management of AAA.


Assuntos
Aneurisma da Aorta Abdominal/cirurgia , Procedimentos Endovasculares/efeitos adversos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Complicações Pós-Operatórias/epidemiologia , Aneurisma da Aorta Abdominal/mortalidade , Mortalidade Hospitalar , Humanos , Incidência , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Resultado do Tratamento
13.
J Vasc Surg ; 75(4): 1440-1449.e5, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34788653

RESUMO

OBJECTIVE: Atherosclerosis obliterans (ASO) is a chronic occlusive arterial disease and the most common type of peripheral arterial disease. Current treatment options like medication and vascularization have limited effects for "no-option" patients, and stem cell therapy is considered a viable option, although its application and efficacy have not been standardized. The objective of this review was to assess the safety and efficacy of autologous stem cell therapy in patients with ASO. METHODS: We performed a literature search of published randomized controlled trials (RCTs) for patients with ASO receiving stem cell therapy without a revascularization option. PubMed, Embase, and the Cochrane Library were searched. This study was conducted by a pair of authors independently and audited by a third author. Data were synthesized with a random-effects model. RESULTS: A total of 630 patients in 12 RCTs were included. The results showed that cell therapy significantly improved total amputation (relative risk [RR], 0.64; 95% confidence interval [CI], 0.47-0.87; P = .004), major amputation (RR, 0.69; 95% CI, 0.50-0.94; P = .02), ankle-brachial index (mean difference [MD], 0.08; 95% CI, 0.02-0.13; P = .004), transcutaneous oxygen tension (MD, 11.52; 95% CI, 3.60-19.43; P = .004), and rest pain score (MD, -0.64; 95% CI, -1.10 to -0.17; P = .007) compared with placebo or standard care. However, current studies showed cell therapy was not superior to placebo or standard care in all-cause death (RR, 0.75; 95% CI, 0.41-1.36; P = .34) and ulcer size (MD, -8.85; 95% CI, -29.05 to 11.36; P = .39). The number of trials included was limited. Moreover, most trials were designed for "no-option" patients, and thus the results should be applied with caution to other patients with peripheral arterial disease. CONCLUSIONS: Patients with ASO can benefit from autologous cell therapy in limb salvage, limb blood perfusion, and rest pain alleviation.


Assuntos
Doença Arterial Periférica , Humanos , Dor , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Transplante de Células-Tronco/efeitos adversos , Transplante Autólogo
14.
Stem Cell Res Ther ; 12(1): 403, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34266474

RESUMO

BACKGROUND: Diabetic limb ischemia is a clinical syndrome and refractory to therapy. Our previous study demonstrated that adipose-derived stem cells (ADSCs) overexpressing glyoxalase-1 (GLO-1) promoted the regeneration of ischemic lower limbs in diabetic mice, but low survival rate, difficulty in differentiation, and tumorigenicity of the transplanted cells restricted its application. Recent studies have found that exosomes secreted by the ADSCs have the advantages of containing parental beneficial factors and exhibiting non-immunogenic, non-tumorigenic, and strong stable characteristics. METHODS: ADSCs overexpressing GLO-1 (G-ADSCs) were established using lentivirus transfection, and exosomes secreted from ADSCs (G-ADSC-Exos) were isolated and characterized to coculture with human umbilical vein endothelial cells (HUVECs). Proliferation, apoptosis, migration, and tube formation of the HUVECs were detected under high-glucose conditions. The G-ADSC-Exos were injected into ischemic hindlimb muscles of type 2 diabetes mellitus (T2DM) mice, and the laser Doppler perfusion index, Masson's staining, immunofluorescence, and immunohistochemistry assays were adopted to assess the treatment efficiency. Moreover, the underlying regulatory mechanisms of the G-ADSC-Exos on the proliferation, migration, angiogenesis, and apoptosis of the HUVECs were explored. RESULTS: The G-ADSC-Exos enhanced the proliferation, migration, tube formation, and anti-apoptosis of the HUVECs in vitro under high-glucose conditions. After in vivo transplantation, the G-ADSC-Exo group showed significantly higher laser Doppler perfusion index, better muscle structural integrity, and higher microvessel's density than the ADSC-Exo and control groups by Masson's staining and immunofluorescence assays. The underlying mechanisms by which the G-ADSC-Exos protected endothelial cells both in vitro and in vivo might be via the activation of eNOS/AKT/ERK/P-38 signaling pathways, inhibition of AP-1/ROS/NLRP3/ASC/Caspase-1/IL-1ß, as well as the increased secretion of VEGF, IGF-1, and FGF. CONCLUSION: Exosomes derived from adipose-derived stem cells overexpressing GLO-1 protected the endothelial cells and promoted the angiogenesis in type 2 diabetic mice with limb ischemia, which will be a promising clinical treatment in diabetic lower limb ischemia.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Exossomos , Tecido Adiposo , Animais , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/terapia , Células Endoteliais da Veia Umbilical Humana , Humanos , Isquemia/terapia , Camundongos , Neovascularização Fisiológica , Células-Tronco
15.
Eur J Vasc Endovasc Surg ; 62(1): 65-73, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34112574

RESUMO

OBJECTIVE: The efficacy and cost effectiveness of atherectomy for femoropopliteal (FP) arterial diseases have not been determined yet. A systematic review and meta-analysis were performed to compare the efficacy and safety between atherectomy combined with balloon angioplasty (BA) and BA alone for patients with de novo FP steno-occlusive lesions. METHODS: The Cochrane Library, Medline, and Embase were used to search for studies evaluating outcomes of atherectomy combined with BA compared with BA alone in FP arterial diseases from inception to July 2020. The methodological quality of the included studies was evaluated with the Cochrane Risk of Bias Tool. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework was used to assess the level of evidence for each outcome. The fixed effects model was chosen to combine the data when I2 < 50%; otherwise, the random effects model was used. Subgroup and sensitivity analyses were performed to further analyse the results. RESULTS: Four RCTs were included. The meta-analysis showed that atherectomy combined with BA was associated with improved technical success rate (risk ratio [RR] 0.22, 95% confidence interval [CI] 0.13-0.38, p < .001; I2 = 0; high quality), reduced bailout stenting (RR 0.15, 95% CI 0.07-0.32, p < .001; I2 = 16%; high quality), and flow limiting dissection (RR 0.24, 95% CI 0.13-0.47, p < .001; I2 = 0; high quality). No statistically significant difference was found in target lesion revascularisation (TLR), primary patency, mortality, major adverse event (MAE), or ankle brachial index (ABI) after one year follow up. CONCLUSION: Compared with BA alone, atherectomy combined with BA may not improve primary patency, TLR, mortality rate, or ABI, but may reduce the need for bailout stenting and the incidence of flow limiting dissection and increase the technical success rate in FP arterial diseases. More studies are warranted to further confirm the conclusion.


Assuntos
Angioplastia com Balão/estatística & dados numéricos , Dissecção Aórtica/epidemiologia , Aterectomia/estatística & dados numéricos , Artéria Femoral/cirurgia , Doença Arterial Periférica/cirurgia , Dissecção Aórtica/etiologia , Dissecção Aórtica/prevenção & controle , Dissecção Aórtica/cirurgia , Angioplastia com Balão/efeitos adversos , Índice Tornozelo-Braço , Aterectomia/efeitos adversos , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Terapia Combinada/estatística & dados numéricos , Seguimentos , Humanos , Doença Arterial Periférica/complicações , Doença Arterial Periférica/diagnóstico , Doença Arterial Periférica/mortalidade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Stents/estatística & dados numéricos , Resultado do Tratamento , Grau de Desobstrução Vascular
16.
Med Oncol ; 38(4): 34, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33660148

RESUMO

Protein interacting with C-kinase 1 (PICK1) is a 415-aa multidomain scaffold protein encoded by the PICK1 gene. Accumulating evidence suggests that PICK1 is involved in the progression of cancer. However, the role of PICK1 in gastric cancer (GC) remains largely unknown. Using integrated analysis of publicly available GC transcriptome data from the Gene Expression Omnibus (GEO) database and immunohistochemistry analysis of samples obtained from clinical GC patients, we found that PICK1 expression was significantly down-regulated in gastric tumor tissues in comparison with adjacent normal tissues. Our analyses also revealed that decreased expression of PICK1 conferred a disadvantage on overall survival time in GC patients. Additionally, PICK1 expression showed a strong association with the epithelial-mesenchymal transition (EMT) pathway, and PICK1 might represent a functional bridge for EMT. Moreover, PICK1 expression was significantly decreased in the EMT subtype of GC and was negatively correlated with the expression of fibronectin 1 (FN1) and myosin light chain 9 (MYL9) mRNAs. Thus, our study provides evidence that PICK1 is a promising biomarker for the molecular etiology of GC.


Assuntos
Proteínas de Transporte/metabolismo , Transição Epitelial-Mesenquimal , Proteínas Nucleares/metabolismo , Neoplasias Gástricas/patologia , Biomarcadores Tumorais/genética , Proteínas de Transporte/genética , Linhagem Celular Tumoral , Regulação para Baixo/genética , Transição Epitelial-Mesenquimal/genética , Fibronectinas/genética , Fibronectinas/metabolismo , Expressão Gênica , Humanos , Cadeias Leves de Miosina/genética , Cadeias Leves de Miosina/metabolismo , Proteínas Nucleares/genética , Prognóstico , Mapas de Interação de Proteínas , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidade
17.
J BUON ; 25(4): 1840-1846, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33099922

RESUMO

PURPOSE: To investigate the effects of long non-coding ribonucleic acid (lncRNA) colorectal cancer (CRC)-associated transcript 2 (CCAT2) expression on proliferation and apoptosis of colorectal cancer (CRC) cells. METHODS: Data of lncRNA expression in CRC were downloaded from the cancer genome atlas (TCGA) database for differential expression and survival analyses, and real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was employed to analyze the expression level of lncRNA CCAT2 in 80 cases of CRC and adjacent tissues collected as well as normal colorectal cells and CRC cell lines selected. The cells successfully transfected were collected for the detection of the effects on apoptosis and proliferation. Then, immunofluorescence assay was performed to measure the protein expression levels of apoptotic protein markers B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax). RESULTS: It was found through differential expression analysis that the expression of lncRNA CCAT2 showed a significant difference in CRC tissues, and CRC patients with a high expression level of lncRNA CCAT2 had poor prognosis. Based on the results of qRT-PCR assay, lncRNA CCAT2 was significantly highly expressed in CRC tissues. After transfection with mimic and NC, its expression was obviously higher in mimic group than that in NC group, and cell lines with over-expressed lncRNA CCAT2 were successfully constructed. The flow cytometry results showed that the proportion of apoptotic cells was 5% in mimic group and about 13% in NC group. According to the results of immunofluorescence assay, Bax was mainly located in the cytoplasm, and the fluorescence intensity was decreased significantly in mimic group, indicating that Bax expression was inhibited. CONCLUSIONS: LncRNA CCAT2 is differentially expressed in CRC, and its expression is significantly upregulated in CRC. LncRNA CCAT2 can promote the growth and proliferation and suppress the apoptosis of CRC cells. The changes in lncRNA CCAT2 expression are associated with poor prognosis.


Assuntos
Neoplasias Colorretais/genética , RNA Longo não Codificante/genética , Apoptose , Proliferação de Células , Neoplasias Colorretais/mortalidade , Feminino , Humanos , Masculino , Análise de Sobrevida , Transfecção
18.
Colloids Surf B Biointerfaces ; 188: 110800, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31958620

RESUMO

In this study, a simple and efficient method to obtain entrapment of mixtures of double enzymes is developed. As a proof of principle, double enzymes (tyrosinase (TYR) and ß-glucosidase (ß-Glu)) were co-immobilized in magnetic alginate-polydopamine (PDA) beads using in situ TYR-mediated dopamine polymerization and internal setting strategy-mediated magnetic alginate-PDA gelation. The leakage of enzymes from the magnetic alginate beads was significantly reduced by exploiting the double network cross-linking of alginate and PDA, which was induced by the d-(+)-Gluconic acid δ-lactone (GDL) and TYR, respectively. The physicochemical properties of the prepared magnetic alginate beads were characterized by Fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD) and scanning electron microscopy (SEM) analysis. After that, the enzymatic reaction conditions and the performance of the entrapped TYR and ß-Glu, such as enzyme kinetics and inhibition kinetics, were investigated. The Michaelis-Menten constants (Km) of the entrapped TYR and ß-Glu were determined as 2.72 and 3.45 mM, respectively. The half-maximal inhibitory concentrations (IC50) of kojic acid and castanospermine for the entrapped TYR and ß-Glu were determined as 13.04 and 56.23 µM, respectively. Finally, the entrapped double enzymes magnetic alginate beads were successfully applied to evaluate the inhibitory potency of six kinds of tea polyphenols extracts. Black tea and white tea showed high inhibition activity against TYR were (36.14 ± 1.43)% and (36.76 ± 2.35)%, respectively, while the black tea and dark tea showed high inhibition activity against ß-Glu were (37.89 ± 6.70)% and (21.28 ± 4.68)%, respectively.


Assuntos
Alginatos/metabolismo , Dopamina/metabolismo , Nanopartículas de Magnetita/química , Monofenol Mono-Oxigenase/metabolismo , beta-Glucosidase/metabolismo , Alginatos/síntese química , Alginatos/química , Cápsulas/química , Cápsulas/metabolismo , Dopamina/química , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Enzimas Imobilizadas/antagonistas & inibidores , Enzimas Imobilizadas/química , Enzimas Imobilizadas/metabolismo , Estrutura Molecular , Monofenol Mono-Oxigenase/antagonistas & inibidores , Monofenol Mono-Oxigenase/química , Tamanho da Partícula , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Polimerização , Polifenóis/química , Polifenóis/farmacologia , Propriedades de Superfície , Chá/química , beta-Glucosidase/antagonistas & inibidores , beta-Glucosidase/química
19.
Biotechnol Appl Biochem ; 66(3): 309-315, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30624798

RESUMO

Oval cells, a kind of hepatic progenitor cell quiescent at normal condition, activates to proliferate and differentiate into hepatocytes under severe and long-term liver injury, which usually raises severe inflammation. However, how oval cell survives in the inflammatory milieu interne is still unclear. Tumor necrosis factor α (TNFα), mimicking inflammatory hepatic milieu interne, was used to treat oval cell line, WB-F344, to test the protective function of matrilin-2. In this study, our data suggested that matrilin-2 prevented TNFα-induced apoptosis in WB-F344 cells via inhibiting ASK1/MKK7/JNK pathway. In conclusion, we determined that matrilin-2 plays the key role in maintaining the survival of oval cell and guarantees its proliferation under various injury factors.


Assuntos
Apoptose/efeitos dos fármacos , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Fator de Necrose Tumoral alfa/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Proteínas Matrilinas/metabolismo , Ratos , Ratos Endogâmicos F344
20.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 40(8): 928-33, 2015 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-26333504

RESUMO

OBJECTIVE: To analyze the histopathological and imaging features for soft tissue liposarcoma of extremities and to provide guide for clinical diagnosis.
 METHODS: Nine patients with soft tissue liposarcoma of extremities received treatment in Qinghai University Affiliated Hospital from October 2012 to October 2014. The imaging features of CT and MRI as well as the histopathological features were retrospectively analyzed. The pattern, size and border of tumor were observed, and the correlation between the pathological features and the imaging features was analyzed.
 RESULTS: Lower limb lesion was found in 8 patients, including the left lower leg, left and right thigh, respectively. One patient had right upper arm lesion, 1 case had bleeding, and 1 case displayed with calcification and liquefaction performance. The CT examination showed low density shadow and linear separated shadow. The ultrasound examination displayed different intensity fat-like echo. There was short signal intensity on T1 weighted imaging and long signal intensity on T2 weighted imaging in MRI.
 CONCLUSION: MRI and other imaging examinations show good performance in detecting the features of soft tissue liposarcoma of extremities, which possess diagnostic value.


Assuntos
Lipossarcoma/diagnóstico , Lipossarcoma/patologia , Neoplasias de Tecidos Moles/diagnóstico , Neoplasias de Tecidos Moles/patologia , Humanos , Imageamento por Ressonância Magnética , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
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