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1.
Med Sci Monit ; 25: 4535-4543, 2019 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-31211767

RESUMO

BACKGROUND This study evaluated the effectiveness of contrast-enhanced ultrasonography for the assessment of skeletal muscle perfusion in diabetes mellites. MATERIAL AND METHODS Electronic databases (Embase, Google Scholar, Ovid, and PubMed) were searched for required articles, and studies were selected by following pre-determined eligibility criteria. Meta-analyses of mean differences or standardized mean differences (SMD) were performed to evaluate the significance of difference in contrast-enhanced ultrasonography measured muscle perfusion indices between patients with diabetes and healthy individuals or between basal and final values of perfusion indices after insulin manipulation or physical exercise in patients with diabetes or healthy individuals. RESULTS There were 15 studies included, with 279 patients with diabetes and 230 healthy individuals in total. The age of the study patients with diabetes mellitus was 55.8 years (95% CI: 49.6 years, 61.9 years) and these patients had disease for 11.4 years (95% CI: 7.7 years, 15.1 years). The percentage of males in group of patients with diabetes was 66% (95% CI: 49%, 84%), body mass index was 29.4 kg/m² (95% CI: 26.5 kg/m², 32.3 kg/m²), hemoglobin A1c was 7.3% (95% CI: 6.7%, 7.9%), and fasting plasma glucose was 149 kg/m² (95% CI: 118 kg/m², 179 kg/m²). Time to peak intensity after provocation was significantly higher in patients with diabetes than in healthy individuals (SMD 1.18 [95% CI: 0.60, 1.76]; P<0.00001). In patients with diabetes, insulin administration did not improve contrast-enhanced ultrasonography measured muscle perfusion indices but exercise improved muscle perfusion but at a level that was statistically non-significant (SMD between basal and post-exercise values (1.03 [95% CI: -0.14, 2.20]; P=0.08). In healthy individuals, lipids in addition to insulin administration was associated with significantly reduced blood volume and blood flow. CONCLUSIONS Our review showed that the use of contrast-enhanced ultrasonography showed that diabetes mellitus was associated with altered muscle perfusion in which insulin-mediated metabolic changes played an important role.


Assuntos
Complicações do Diabetes/diagnóstico por imagem , Músculo Esquelético/diagnóstico por imagem , Imagem de Perfusão/métodos , Glicemia/metabolismo , Índice de Massa Corporal , China , Meios de Contraste , Diabetes Mellitus/metabolismo , Exercício Físico , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Insulina/sangue , Masculino , Pessoa de Meia-Idade , Ultrassonografia/métodos
2.
Eur J Med Chem ; 154: 324-340, 2018 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-29843103

RESUMO

Two series of thieno[2,3-d]pyrimidine derivatives bearing a dithiocarbamate side chain at the C2 position were synthesized and evaluated for cytotoxic activity in human lung cancer A549 and colon cancer HCT-116 cell lines. Compound 3n exhibited the most cytotoxic effect on A549 cells with an IC50 value of 4.87 µM, inducing a cell cycle arrest at G2/M phase and activating the spindle assembly checkpoint (SAC). To identify the target protein(s) of 3n, we incorporated biotin with 3n through a three-carbon chain and an amide bond to synthesize probe 10. The targeted proteins were pulled down from the A549 total cell lysate by biotin-streptavidin affinity purification and analyzed by mass spectrometry. Tubulin was the only protein identified, which is related to the SAC and directly binds to probe 10 both in vivo and in vitro. Furthermore, compound 3n inhibited tubulin polymerization in vitro in a dose-dependent manner, competed with taxol in binding to tubulin, exerting cytotoxic activity toward taxol-resistant A549 cells. These results demonstrate that thieno[2,3-d]pyrimidine derivative 3n exhibits cytotoxicity in cancer cells by targeting tubulin to activate the SAC and potentially acts as a therapeutic lead compound for taxol-resistant cancers.


Assuntos
Antineoplásicos/farmacologia , Pirimidinas/farmacologia , Tiocarbamatos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Estrutura Molecular , Pirimidinas/síntese química , Pirimidinas/química , Relação Estrutura-Atividade , Tiocarbamatos/química , Células Tumorais Cultivadas
3.
Eur J Med Chem ; 127: 137-146, 2017 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-28039772

RESUMO

Two new platinum(II) complexes 7a and 7b with methyl hydrazinecarbodithioate derivatives of indolin-2-one have been prepared and characterized by single-crystal X-ray diffraction, NMR spectroscopy and mass spectrometry. Antiproliferative activity of the two complexes and their ligands 6a and 6b against HCT-116, MCF-7 and MDA-MB-231 cell lines was determined by the MTS assay. Complexes 7a and 7b exhibited stronger antiproliferative activity against three cell lines than compounds 6a and 6b (IC50, 1.89-5.60 versus 6.52-35.13 µM). Moreover, treatment of HCT-116 cells with the complexes resulted in an obvious sub-G1 peak by cell cycle profile analysis, and an increase of cleaved PARP1 and caspases 3, 7, and 9 by immunoblotting analysis. Live cell imaging showed that nucleus shrinkage and condensation started to appear when MCF-7 cells were treated with 7a for 8 h. Fluorescent spectrophotometric analysis revealed that the complexes physically associated with calf thymus DNA. Competitive DNA binding assays uncovered that the complexes non-covalently bind to DNA. Taken together, our results indicated that the two new platinum(II) complexes 7a and 7b non-covalently bind to DNA with high affinity and exhibit cytotoxicity against cancer cells by inducing apoptosis.


Assuntos
Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Hidrazinas/química , Indóis/química , Compostos Organoplatínicos/síntese química , Compostos Organoplatínicos/farmacologia , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Apoptose/efeitos dos fármacos , Bovinos , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Técnicas de Química Sintética , Cristalografia por Raios X , DNA/metabolismo , Ensaios de Seleção de Medicamentos Antitumorais , Células HCT116 , Humanos , Células MCF-7 , Modelos Moleculares , Conformação Molecular , Compostos Organoplatínicos/química , Compostos Organoplatínicos/metabolismo , Relação Estrutura-Atividade
4.
Insect Sci ; 24(5): 753-767, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27311916

RESUMO

Serine proteases play important roles in digestion and immune responses during insect development. In the present study, the serine protease gene BmSP36, which encodes a 292-residue protein, was cloned from the midgut cells of Bombyx mori. BmSP36 contains an intact catalytic triad (H57, D102 and S195) and a conserved substrate-binding site (G189, H216 and G226), suggesting that it is a serine protease with chymotrypsin-like specificity. The temporal and spatial expression patterns of BmSP36 indicated that its messenger RNA and protein expression mainly occurred in the midgut at the feeding stages. Western blotting, immunofluorescence and liquid chromatography-tandem mass spectrometry analyses revealed secretion of BmSP36 protein from epithelial cells into the midgut lumen. The transcriptional and translational expression of BmSP36 was down-regulated after starvation but up-regulated after refeeding. Moreover, expression of the BmSP36 gene could be up-regulated by a juvenile hormone analogue. These results enable us to better define the potential role of BmSP36 in dietary protein digestion at the feeding stages during larval development.


Assuntos
Bombyx/enzimologia , Proteínas de Insetos/metabolismo , Serina Proteases/metabolismo , Sequência de Aminoácidos , Animais , Western Blotting , Proteínas Alimentares/metabolismo , Digestão , Imunofluorescência , Privação de Alimentos , Trato Gastrointestinal/enzimologia , Regulação da Expressão Gênica , Hormônios Juvenis , Larva/enzimologia , Pupa/enzimologia , Reação em Cadeia da Polimerase em Tempo Real
5.
Insect Sci ; 23(6): 835-842, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26013638

RESUMO

Pupae inside cocoons rarely suffer from disease. It is apparent that some factors in the cocoon exert antimicrobial effects whereby the pupae inside can be protected from microbial infection. In the present study, we investigated the expression of cocoon protease inhibitors using immunoblotting and activity staining. Enzymatic hydrolysis of cocoon proteins in vitro was performed to characterize their roles in protecting the cocoon from microbial proteases. We found that some protease inhibitors, particularly trypsin inhibitor-like (TIL)-type protease inhibitors, can be secreted into the cocoon layer during the spinning process, thereby providing effective protection to the cocoon and pupa by inhibiting the extracellular proteases that can be secreted by pathogens.


Assuntos
Bombyx/metabolismo , Proteínas de Insetos/metabolismo , Inibidores de Serina Proteinase/metabolismo , Seda/análise , Animais , Bombyx/crescimento & desenvolvimento , Bombyx/microbiologia , Larva/metabolismo , Pupa/metabolismo , Pupa/microbiologia , RNA Mensageiro/metabolismo , Inibidores de Serina Proteinase/genética
7.
Zhong Xi Yi Jie He Xue Bao ; 3(1): 28-30, 2005 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-15644156

RESUMO

OBJECTIVE: To evaluate the therapeutic effect of transplantation of autologous bone marrow mononuclear cells combined with traditional Chinese medicine for the treatment of limb ischemia. METHODS: Twenty-three patients with limb ischemia were treated. G-CSF was used to stimulate the bone marrow. The mononuclear cells were separated from the aspirated bone marrow fluid in the stem cell studio. The cell amount was above 1x10(9). The transplantation was performed by the way of intra-muscular multi-injection. Traditional Chinese medicine for replenishing qi to activate blood was prescribed from the first day after operation. The pain, poikilothermia, ulcer or necrosis and ankle/brachial index (ABI) of the ischemic limb were evaluated before and after the treatment. RESULTS: The pain score and poikilothermia score decreased one month after the transplantation, with distinct differences as compared with the scores before the treatment (P<0.05). The ABI increased gradually after the treatment, and one month after the treatment, it was 0.15 higher than that before the treatment. CONCLUSION: Transplantation of autologous bone marrow mononuclear cells combined with traditional Chinese medicine can decrease the symptoms and signs of severe lower limb ischemia effectively, and improve the circulation of the ischemic area.


Assuntos
Transplante de Medula Óssea , Isquemia/terapia , Extremidade Inferior/irrigação sanguínea , Fitoterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Arteriopatias Oclusivas/terapia , Transplante de Medula Óssea/métodos , Terapia Combinada , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Humanos , Leucócitos Mononucleares/transplante , Masculino , Pessoa de Meia-Idade , Transplante Autólogo
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