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1.
Theranostics ; 11(8): 3796-3812, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33664862

RESUMO

Rationale: Mechanisms underlying the compromised bone formation in type 1 diabetes mellitus (T1DM), which causes bone fragility and frequent fractures, remain poorly understood. Recent advances in organ-specific vascular endothelial cells (ECs) identify type H blood vessel injury in the bone, which actively direct osteogenesis, as a possible player. Methods: T1DM was induced in mice by streptozotocin (STZ) injection in two severity degrees. Bony endothelium, the coupling of angiogenesis and osteogenesis, and bone mass quality were evaluated. Insulin, antioxidants, and NADPH oxidase (NOX) inhibitors were administered to diabetic animals to investigate possible mechanisms and design therapeutic strategies. Results: T1DM in mice led to the holistic abnormality of the vascular system in the bone, especially type H vessels, resulting in the uncoupling of angiogenesis and osteogenesis and inhibition of bone formation. The severity of osteopathy was positively related to glycemic levels. These pathological changes were attenuated by early-started, but not late-started, insulin therapy. ECs in diabetic bones showed significantly higher levels of reactive oxygen species (ROS) and NOX 1 and 2. Impairments of bone vessels and bone mass were effectively ameliorated by treatment with anti-oxidants or NOX2 inhibitors, but not by a NOX1/4 inhibitor. GSK2795039 (GSK), a NOX2 inhibitor, significantly supplemented the insulin effect on the diabetic bone. Conclusions: Diabetic osteopathy could be a chronic microvascular complication of T1DM. The impairment of type H vessels by NOX2-mediated endothelial oxidative stress might be an important contributor that can serve as a therapeutic target for T1DM-induced osteopathy.


Assuntos
Osso e Ossos/irrigação sanguínea , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , NADPH Oxidase 2/metabolismo , Animais , Antioxidantes/farmacologia , Fenômenos Biomecânicos , Osso e Ossos/patologia , Osso e Ossos/fisiopatologia , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 1/fisiopatologia , Células Endoteliais/fisiologia , Insulina/administração & dosagem , Insulina/uso terapêutico , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Terapia de Alvo Molecular , NADPH Oxidase 2/antagonistas & inibidores , Neovascularização Fisiológica/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Osteoporose/etiologia , Osteoporose/patologia , Osteoporose/fisiopatologia , Estresse Oxidativo , Medicina de Precisão
2.
Chem Commun (Camb) ; 51(53): 10684-6, 2015 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-26051473

RESUMO

A novel azopyridine-based Ru(II) complex [Ru(bpy)2(L1)2](2+) (bpy = 2,2'-bipyridine, L1 = 4,4'-azopyridine) was designed and synthesized as a potential glutathione (GSH)-responsive photoactivated chemotherapy (PACT) agent, the DNA covalent binding capability of which can only be activated after GSH reduction and visible light irradiation.


Assuntos
2,2'-Dipiridil/química , Complexos de Coordenação/química , DNA/química , Glutationa/química , Rutênio/química , Luz , Oxirredução , Teoria Quântica
3.
Hum Immunol ; 71(9): 899-904, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20600448

RESUMO

Human leukocyte antigen-G (HLA-G) is a potent immunosuppressive molecule that induces functional silencing of both innate and adaptive immune responses. The relevance of the aberrant HLA-G expression in malignant contexts has been intensively investigated. However, its expression status and clinical significance in bladder cancer remain to be elucidated. In the current study, HLA-G expression in 75 primary bladder transitional cell carcinoma (TCC) lesions was analyzed with immunohistochemistry, and relationship between HLA-G expression and clinical parameters, including disease stage was evaluated. Plasma soluble HLA-G levels were analyzed in 15 TCC patients and 109 normal controls. Data revealed that HLA-G was expressed in 68.0% (51/75) primary TCC lesions, whereas it was undetectable in adjacent normal bladder tissues. The proportion of HLA-G expression in TCC samples varied from negative to 100%, and no significant association was observed for the HLA-G expression status with the patient age, gender, and disease stage. Furthermore, no significance for sHLA-G levels was observed between the TCC patients and normal controls (median 10.75 vs 8.69 U/ml, p = 0.578). Given its immunotolerant properties, our finding suggested that lesion HLA-G expression upregulated in bladder TCC lesions might be an additional mechanism for tumor cells evading from host immunosurveillance; however, its clinical relevance needs further investigation.


Assuntos
Carcinoma de Células de Transição/metabolismo , Antígenos HLA/metabolismo , Antígenos de Histocompatibilidade Classe I/metabolismo , Regulação para Cima/imunologia , Neoplasias da Bexiga Urinária/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/imunologia , Carcinoma de Células de Transição/patologia , Membrana Celular/metabolismo , Citoplasma/metabolismo , Feminino , Antígenos HLA/sangue , Antígenos HLA-G , Antígenos de Histocompatibilidade Classe I/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias da Bexiga Urinária/imunologia , Neoplasias da Bexiga Urinária/patologia
4.
Zhonghua Yi Xue Za Zhi ; 90(16): 1120-2, 2010 Apr 27.
Artigo em Chinês | MEDLINE | ID: mdl-20646431

RESUMO

OBJECTIVE: To compare the clinical efficacy and safety of nephrectomy versus radical nephrectomy for renal cell carcinoma (RCC). METHODS: A total of 134 patients with renal carcinoma without metastasis in lymphatic system and distant sites were recruited. In random, 69 cases of renal cell carcinoma were elected for nephrectomy and the others radical nephrectomy. The operating time, blood loss, fasting time, postoperative hospital stay, information of tumor recurrence and metastasis, survival time without tumor, survival rate and perioperative complication were compared between two groups. RESULTS: In cases of nephrectomy, the operating time ranged from 60 - 135 minutes and blood loss 70 - 100 ml. In 4 cases, membrana pleuro-peritonealis was damaged. The fasting time ranged from 6 - 24 hours and postoperative hospital stay 5 - 8 days; the staging of all 69 cases was detected; follow-up studies ranged from 5 - 15 years, finding 1 case tumor metastasis in adrenal body and 1 case recurrent tumor in cases of radical nephrectomy, operating time ranged from 105 - 185 minutes and blood loss 150 - 2000 ml. Membrana pleuro-peritonealis was breached in 3 cases. The fasting time ranged from 12 - 90 hours and postoperative hospital stay 8 - 12 days. The staging of all 65 cases was detected. Follow-up studies of 5 - 15 years revealed 1 case of tumor metastasis in brain and 1 case of recurrent tumor. There was no significant difference in perioperative complication, tumor recurrence, tumor metastasis and survival time without tumor between those two groups (P > 0.05). The blood loss, operating time, fasting and postoperative hospital stay were less than that in radical nephrectomy group (P < 0.05). CONCLUSION: In patients without metastasis in lymphatic system and distant sites, nephrectomy is both effective and safe. It has the advantages of a short operating time, a short postoperative hospital stay and less damage and blood loss than radical nephrectomy.


Assuntos
Carcinoma de Células Renais/cirurgia , Neoplasias Renais/cirurgia , Nefrectomia/métodos , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
5.
Zhonghua Yi Xue Za Zhi ; 89(48): 3417-9, 2009 Dec 29.
Artigo em Chinês | MEDLINE | ID: mdl-20223117

RESUMO

OBJECTIVE: To discuss the causes of common complications of ureteroscopy and how to prevent them. METHODS: A total of 768 cases of common complications of ureteroscopy were retrospectively analyzed from February 2004 to February 2009. RESULTS: The intra-operative complications were failed entry (n = 6, 0.78%), ureterostoma injury and ureterostoma submucosa pseudocana (n = 12, 1.56%), ureteral perforation (n = 16, 2.08%), stone displacement (n = 13, 1.87%) and ureteral mucosa evulsion (n = 3, 0.39%). And the post-operative complications were lumbago or renal colic (n = 11, 1.43%), infection (n = 9, 1.17%)and severe hematuria (n = 5, 0.65%). CONCLUSION: Skillful operative techniques and strict indications are key to reducing complications of ureteroscopy.


Assuntos
Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Ureteroscopia/efeitos adversos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
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