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1.
Guang Pu Xue Yu Guang Pu Fen Xi ; 36(8): 2522-6, 2016 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-30074357

RESUMO

3,4-thiophenedicarboxylic acid (3,4-H2tdc) as the first ligand, 1,10-phenanthroline (phen) as the auxiliary ligand, three complexes Ln2(Htdc)2(tdc)2(phen)2(H2O)4(Ln=Eu 1, Gd 2, Tb 3) were synthesized with hydrothermal method. Single-crystal X-ray diffraction analysis reveals that complexes 1-3 were isostructural crystallize and both of complexes are binuclear molecules. In the complexes 1-3, the coordination number is nine. Each metal is bound to two 3, 4-tdc ligand, one 3,4-Htdc ligand, one phen and two water molecule. Complexes 1 and 3 display the red and green light under UV lamp, corresponding the characteristic peaks from 619 nm (5D0→7F2) and 545 nm (5D4→7F5). Complex 2 expresses a broad band at 425 nm is attributed to π*→π transition. Furthermore, under the excitation wavelength of 329 nm, the effects of different solvents on complex 1 was discussed and complex 1 could be a potential luminescent probe for detecting nitrobenzene through fluorescence quenching mechanism.

2.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(8): 2208-11, 2015 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-26672295

RESUMO

Two new complexes, {[Eu3(bidC)4(phen)2(NO3)] · 2H2O}n, (1) and [Tb2(bidC)3(H2O)2] (2) (bidc=benzimidazole-dicarboxylate, phen=1, 10-phenanthrolIne) were synthesized. Complex 1 shows 1D chain structure. The asymmetric unit of 1 contains three crystallographically different Eu(3+), Eu(1)O6N2, Eu(2)O8 and Eu(3)O6N2. Complex 2 reveals 2D structure. It contains two crystallographically similar Tb(3+), Tb(1)O8 and Tb(2)O8. Complex 1 displays the emission peaks at 581, 593, 615, 654 and 702 nm, corresponding to the (5)D0-->(7)FJ (J=0-4) transitions of Eu(3+). The most intense emission at 615 nm is attributed to the (5)D-->(7)F2 transition, implies a red emission light of 1. The intensity rations I((5)D0/(7)F2)/I((5)D0/(7)F1) is about 2.5, indicating the chemical environment around Eu(3+) does not have an inversion center. Complex 2 exhibits four emission peaks at 492, 545, 584 and 622 nm, corresponding to the (5)D4-->(7)FJ (J=6-3) transitions of Tb(3+). The emission band at 545 nm corresponds to the (5)D4-->(7)F5 transition of the Tb(3+), which gives an intense green luminescence output for the solid sample. Notably, the solvent-dependent luminescence behavior of complexes 1 and 2 was discussed. They show highly selective for nitrobenzene via a fluorescence quenching mechanism. The highly selective and sensitive sensing nitrobenzene leads to its application in environmental system.

3.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(12): 3369-74, 2015 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-26964212

RESUMO

Hyperspectral imaging technology has great potential in the identification of crop varieties because it contains both image information and spectral information for the object. But so far most studies only used the spectral information, the image information has not been effectively utilized. In this study, hyperspectral images of single seed of three types including strong gluten wheat, medium gluten wheat, and weak gluten wheat were collected by near infrared hyperspectra imager, 12 morphological characteristics such as length, width, rectangularity, circularity and eccentricity were extracted, the average spectra of endosperm and embryo were acquired by the mask which was created by image segmentation. Partial least squares discriminant analysis (PLADA) and least squares support vector machine (LSSVM) were used to construct the classification model with image information, results showed that the binary classification accuracy between strong gluten wheat and weak gluten wheat could achieve 98%, for strong gluten wheat and medium gluten wheat, it was only 74.22%, which indicated that hyperspectral images could reflect the differences of varieties, but the accuracy might be poor when recognizing the varieties just by image information. Soft independent modeling of class analogy (SIMCA), PLSDA and LSSVM were used to established the classification model with spectral information, the classification effect of endosperm is slightly better than the embryo, it demonstrated that the grain shape could influence the classification accuracy. Then, we fused the spectral and image information, SIMCA, PLSDA and LSSVM were used to established the identification model, the fusion model showed better performance than the individual image model and spectral model, the classification accuracy which used the PLSDA raise from 96.67% to 98.89%, it showed that digging the morphological and spectral characteristics of the hyperspectral image could effectively improve the classification effect.


Assuntos
Glutens/análise , Espectroscopia de Luz Próxima ao Infravermelho , Triticum/classificação , Análise Discriminante , Análise dos Mínimos Quadrados , Modelos Teóricos , Máquina de Vetores de Suporte
4.
Hum Mol Genet ; 21(19): 4237-52, 2012 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-22752410

RESUMO

Various small molecule pharmacologic agents with different known functions produce similar outcomes in diverse Mendelian and complex disorders, suggesting that they may induce common cellular effects. These molecules include histone deacetylase inhibitors, 4-phenylbutyrate (4PBA) and trichostatin A, and two small molecules without direct histone deacetylase inhibitor activity, hydroxyurea (HU) and sulforaphane. In some cases, the therapeutic effects of histone deacetylase inhibitors have been attributed to an increase in expression of genes related to the disease-causing gene. However, here we show that the pharmacological induction of mitochondrial biogenesis was necessary for the potentially therapeutic effects of 4PBA or HU in two distinct disease models, X-linked adrenoleukodystrophy and sickle cell disease. We hypothesized that a common cellular response to these four molecules is induction of mitochondrial biogenesis and peroxisome proliferation and activation of the stress proteome, or adaptive cell survival response. Treatment of human fibroblasts with these four agents induced mitochondrial and peroxisomal biogenesis as monitored by flow cytometry, immunofluorescence and/or western analyses. In treated normal human fibroblasts, all four agents induced the adaptive cell survival response: heat shock, unfolded protein, autophagic and antioxidant responses and the c-jun N-terminal kinase pathway, at the transcriptional and translational levels. Thus, activation of the evolutionarily conserved stress proteome and mitochondrial biogenesis may be a common cellular response to such small molecule therapy and a common basis of therapeutic action in various diseases. Modulation of this novel therapeutic target could broaden the range of treatable diseases without directly targeting the causative genetic abnormalities.


Assuntos
Adrenoleucodistrofia/tratamento farmacológico , Tratamento Farmacológico , Ácidos Hidroxâmicos/uso terapêutico , Hidroxiureia/uso terapêutico , Fenilbutiratos/uso terapêutico , Proteoma/metabolismo , Tiocianatos/uso terapêutico , Adrenoleucodistrofia/genética , Adrenoleucodistrofia/metabolismo , Adrenoleucodistrofia/fisiopatologia , Linhagem Celular , Humanos , Isotiocianatos , Renovação Mitocondrial/efeitos dos fármacos , Proteoma/genética , Bibliotecas de Moléculas Pequenas/uso terapêutico , Sulfóxidos
5.
Dig Dis Sci ; 59(4): 778-86, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24162270

RESUMO

BACKGROUND: The early diagnosis of pancreas allograft dysfunction is crucial for the management and long-term survival of transplanted pancreases. We investigated whether intercellular adhesion molecular-1 (ICAM-1), Fas, and Fas ligand (FasL) can be used as novel biomarkers of acute pancreaticoduodenal allograft dysfunction in pigs. METHODS: Forty outbred landraces were randomly divided into three groups. In the control group (8 pigs), a sham operation was performed but no drugs were administered. In groups 1 and 2 (8 pairs each), pancreaticoduodenal transplantation was performed, with the latter administered immunosuppressive drugs and the former not administered drugs. The expression of ICAM-1, Fas, and FasL mRNA in the peripheral vein blood was assessed by flow cytometry and RT-PCR, pre-transplant and on days 1, 3, 5, and 7 after transplantation. Simultaneously, the levels of glucose, insulin, and glucagon in the serum of the recipients were evaluated. The allograft pancreas tissue was obtained to assess the pathological damage and the expression of Fas and FasL by immunohistochemistry. RESULTS: On the first 7 days after transplantation, ICAM-1, Fas, and FasL mRNA expression in the blood leukocytes of the recipient increased significantly in groups 1 and 2 compared with the control group (P < 0.01). However, the levels in group 2 were significantly lower than those in group 1 (P < 0.05). Interestingly, the FasL expression increased but the Fas expression decreased gradually in the graft pancreas tissue during the first week after transplantation in both groups 1 and 2 compared with the control group (P < 0.05). The levels of serous glucose, insulin, and glucagon in groups 1 and 2 obviously changed on day 1 after transplantation but returned to normal on day 2. The recipient's pancreas pathological sections did not exhibit any rejection changes on days 1 and 3 after transplantation but showed rejection damage on days 5 and 7. CONCLUSION: ICAM-1, Fas, and FasL were found to be sensitive biomarkers of acute pancreas allograft dysfunction after pancreaticoduodenal transplantation in pigs, and their monitoring could be used to evaluate the effectiveness of the immunosuppression therapy.


Assuntos
Biomarcadores/sangue , Proteína Ligante Fas/sangue , Rejeição de Enxerto/diagnóstico , Molécula 1 de Adesão Intercelular/sangue , Receptor fas/sangue , Aloenxertos , Animais , Duodeno/transplante , Glucagon/sangue , Rejeição de Enxerto/patologia , Insulina/sangue , Leucócitos/química , Pâncreas/patologia , Transplante de Pâncreas , Suínos
6.
RSC Adv ; 14(15): 10209-10218, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38544936

RESUMO

In this study, we discuss the tunability of valley splitting using first-principles calculations with a monolayer MoTe2 and layered ferromagnetic MnS2 heterostructure as an example. We observe that, due to the magnetic proximity effect (MPE) at the interface, a monolayer of MoTe2 can exhibit a significant valley splitting of 55.2 meV. The production of the interlayer dipoles with spin-adapted configuration could be the origin of MPE at the interface. Furthermore, the valley splitting can be regulated continuously by the perpendicular electric field and biaxial strain. Interestingly, the valley splitting increases with the increasing induced magnetic moments in MoTe2 by applying an electric field while the inverse laws are presented by applying biaxial strains, which indicates that the mechanisms of valley splitting manipulating in these two ways are quite different. The calculation results suggest that the electric field influences the electric dipole distributions at the interface, which determines the induced magnetic moments in monolayer MoTe2, and results in valley splitting variations. However, biaxial strains not only affect MPE at the interface but also the intrinsic spin splitting caused by spin-orbital coupling (SOC) effects of monolayer MoTe2 itself and the latter is even the dominating mechanism of valley splitting variations.

7.
Front Pharmacol ; 15: 1409321, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39070785

RESUMO

Background: Ferroptosis has been proven to contribute to the progression of myocardial ischemia/reperfusion (I/R) injury and can be inhibited or promoted by ATF3. Short-chain fatty acids (SCFAs) have shown benefits in various cardiovascular diseases with anti-inflammatory and antioxidant effects. However, the impact of SCFAs on ferroptosis in ischemic-stimulated cardiomyocytes remains unknown. This study aimed to investigate the effect of SCFAs on cardiomyocyte ferroptosis, the expression of ATF3, and its potential upstream regulators. Methods and results: The expression of ATF3, ferroptosis pathway geneset (FPG), and geneset of potential regulators for ATF3 (GPRA, predicted by the PROMO database) was explored in the public human myocardial infarction single-cell RNA-seq (sma) dataset. Cardiomyocyte data was extracted from the dataset and re-clustered to explore the FPG, ATF3, and GPRA expression patterns in cardiomyocyte subclusters. A dose-dependent toxic experiment was run to detect the suitable dose for SCFA treatment. The erastin-induced ferroptosis model and hypoxia-reoxygenation (H/R) model (10 h of hypoxia followed by 6 h of reoxygenation) were adopted to assess the effect of SCFAs via the CCK8 assay. Gene expression was examined via RT-PCR and western blot. Ferroptosis markers, including lipid peroxides and Fe2+, were detected using the liperfluo and ferroOrange probes, respectively. In the sma dataset, upregulated ferroptosis pathway genes were mainly found in the infarction-stimulated cardiac cells (border zone and fibrotic zone), particularly the cardiomyocytes and adipocytes. The ATF3 and some of its potential transcription factors (VDR, EGR3, PAX5, and SP1) can be regulated by SCFA. SCFA can attenuate erastin-induced lipid peroxidation in cardiomyocytes. SCFA treatment can also reverse erastin-induced Fe2+ increase but may strengthen the Fe2+ in the H/R model. We also precisely defined a ferroptosis subcluster of cardiomyocytes (CM09) that highly expressed FPG, ATF3, and GPRA. Conclusion: The ATF3 and the ferroptosis pathway are elevated in cardiomyocytes of injury-related cardiac regions (border zone, ischemic zone, and fibrotic zone). SCFA can attenuate cardiomyocyte ferroptosis and regulate the expression of ATF3. Our study offers novel insights into the potential targets of SCFAs in the cardiovascular system.

8.
Environ Pollut ; 271: 116365, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33388681

RESUMO

Nitrification inhibitors (NIs) have been shown to be an effective tool to mitigate direct N2O emissions from soils. However, emerging findings suggest that NIs may increase soil ammonia (NH3) volatilization and, subsequently, indirect N2O emission. A quantitative synthesis is lacking to evaluate how NIs may affect NH3 volatilization and the overall N2O emissions under different environmental conditions. In this meta-analysis, we quantified the responses of NH3 volatilization to NI application with 234 observations from 89 individual studies and analysed the role of experimental method, soil properties, fertilizer/NI type, fertilizer application rate and land use type as explanatory factors. Furthermore, using data sets where soil NH3 emission and N2O emission were measured simultaneously, we re-evaluated the effect of NI on overall N2O emissions including indirect N2O emission from NH3 volatilization. We found that, on average, NIs increased NH3 volatilization by 35.7% (95% CI: 25.7-46.7%) and increased indirect N2O emission from NH3 emission (and subsequent N deposition) by 2.9%-15.2%. Responses of NH3 volatilization mainly varied with experimental method, soil pH, NI type and fertilizer type. The increase of NH3 volatilization following NI application showed a positive correlation with soil pH (R2 = 0.04, n = 234, P < 0.05) and N fertilizer rate (R2 = 0.04, n = 187, P < 0.05). When the indirect N2O emission was considered, NI's N2O mitigation effect decreased from 48.0% to 39.7% (EF = 1%), or 28.2% (EF = 5%). The results indicate that using DMPP with ammonium-based fertilizer in low pH, high SOC soils would have a lower risk for increasing NH3 volatilization than using DCD and nitrapyrin with urea in high pH, lower SOC soil. Furthermore, reducing N application rate may help to improve NIs' overall N2O emission mitigation efficiency and minimize their impact on NH3 volatilization.


Assuntos
Amônia , Nitrificação , Agricultura , Amônia/análise , Fertilizantes/análise , Nitrogênio , Óxido Nitroso/análise , Solo , Volatilização
9.
J Anal Test ; 5(4): 314-326, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631199

RESUMO

The outbreak of severe pneumonia at the end of 2019 was proved to be caused by the SARS-CoV-2 virus spreading out the world. And COVID-19 spread rapidly through a terrible transmission way by human-to-human, which led to many suspected cases waiting to be diagnosed and huge daily samples needed to be tested by an effective and rapid detection method. With an increasing number of COVID-19 infections, medical pressure is severe. Therefore, more efficient and accurate diagnosis methods were keen urgently established. In this review, we summarized several methods that can rapidly and sensitively identify COVID-19; some of them are widely used as the diagnostic techniques for SARS-CoV-2 in various countries, some diagnostic technologies refer to SARS (Severe Acute Respiratory Syndrome) or/and MERS (Middle East Respiratory Syndrome) detection, which may provide potential diagnosis ideas.

10.
Vaccine ; 39(8): 1241-1247, 2021 02 22.
Artigo em Inglês | MEDLINE | ID: mdl-33516600

RESUMO

Without approved vaccines and specific treatments, COVID-19 is spreading around the world with above 26 million cases and approximately 864 thousand deaths until now. An efficacious and affordable vaccine is urgently needed. The Val308 - Gly548 of spike protein of SARS-CoV-2 linked with Gln830 - Glu843 of Tetanus toxoid (TT peptide) (designated as S1-4) and without TT peptide (designated as S1-5) were expressed and renatured. The antigenicity and immunogenicity of S1-4 were evaluated by Western Blotting (WB) in vitro and immune responses in mice, respectively. The protective efficiency was measured preliminarily by microneutralization assay (MN50). The soluble S1-4 and S1-5 protein was prepared to high homogeneity and purity. Adjuvanted with Alum, S1-4 protein stimulated a strong antibody response in immunized mice and caused a major Th2-type cellular immunity supplemented with Th1-type immunity. Furthermore, the immunized sera could protect the Vero E6 cells from SARS-CoV-2 infection with neutralizing antibody titer 256. Recombinant SARS-CoV-2 RBD with a built in T helper epitope could stimulate both strong humoral immunity supplemented with cellular immunity in mice, demonstrating that it could be a promising subunit vaccine candidate.


Assuntos
Anticorpos Antivirais/imunologia , Vacinas contra COVID-19/imunologia , Epitopos de Linfócito T/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Formação de Anticorpos , COVID-19 , Feminino , Humanos , Camundongos , Camundongos Endogâmicos BALB C , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus/genética
11.
Org Chem Front ; 7(22): 3608-3615, 2020 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-33184589

RESUMO

Two formal syntheses and one total synthesis of fostriecin (1) have been achieved, as well as, the synthesis of its related congener dihydro-dephospho-fostriecin. All the routes use the Sharpless dihydroxylation to set the absolute stereochemistry at C-8/9 positions and a Leighton allylation to set the C-5 position of the natural product. In the formal syntheses a Noyori transfer hydrogenation of an ynone was used to set the C-11 position while the total synthesis employed a combination of asymmetric dihydroxylation and Pd-π-allyl reduction to set the C-11 position. Finally in the total synthesis, a trans-hydroboration of the C-12/13 alkyne was used in combination with a Suzuki cross coupling to establish the Z,Z,E-triene of fostriecin (1).

12.
Hepatobiliary Pancreat Dis Int ; 8(3): 294-9, 2009 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-19502171

RESUMO

BACKGROUND: During hepatectomy, a period of ischemia and restoration of the blood supply can result in hepatic ischemia-reperfusion injury (IRI). Current research indicates that erythropoietin (EPO) has a protective effect in animal models of cerebral ischemia, myocardial infarction, and renal IRI. However there is lack of research into the role of EPO in hepatic IRI. This study aimed to explore the role of EPO in hepatic IRI and its possible mechanism of action. METHODS: Thirty male Sprague-Dawley rats were divided into three groups: (1) ten rats in the experimental group were given 1000 IU/kg EPO one day before the operation; (2) ten rats in a control group were given normal saline preoperatively as a placebo; and (3) ten rats served as a sham-operated group. Hepatic IRI was induced by occluding the hepatic arteries of the three cephalad hepatic segments and the portal vein for about 45 minutes, while in the sham-operated group only laparotomy was performed. The levels of ALT and AST were tested 24 hours pre- and post-operation. All rats were sacrificed 24 hours after the operation to assess the pathologic changes in the liver and measure the expression of heme oxygenase-1 (HO-1) through Western blotting and RT-PCR. RESULTS: Hepatic IRI was markedly mitigated in the experimental group as compared with the control group. Moreover, the expression of HO-1 at the level of both transcription and protein increased prominently (P<0.05) in the experimental group. CONCLUSION: These results demonstrate that EPO can up-regulate HO-1 in liver tissues and accordingly decrease hepatic injury through its anti-inflammatory property.


Assuntos
Eritropoetina/uso terapêutico , Hepatectomia/efeitos adversos , Fígado/irrigação sanguínea , Cuidados Pré-Operatórios , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/prevenção & controle , Alanina Transaminase/sangue , Animais , Aspartato Aminotransferases/sangue , Western Blotting , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Fígado/enzimologia , Fígado/patologia , Masculino , Período Pós-Operatório , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima
13.
Nanoscale Adv ; 1(4): 1482-1488, 2019 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-36132614

RESUMO

In this paper, the fluorescence signal of poly(A) DNA-templated Au nanoclusters (AuNCs) is found to be greatly quenched by photoinduced electron transfer (PET) when they are close to guanine (G)-rich DNA. Based on the findings, we have designed a low-cost fluorescence biosensing strategy for the sensitive detection of DNA. Highly luminescent and photo-stable poly(A) DNA-AuNCs were utilized as the fluorescent indicator and G-rich DNA was utilized as the fluorescent quencher. In the absence of target DNA, DNA-AuNCs failed to hybridize with the G-rich DNA and did not form the duplex DNA structure. Strong fluorescence intensity at 475 nm was observed due to the DNA-AuNCs being far away from the G-rich DNA. However, in the presence of target DNA, the DNA-AuNCs together with G-rich DNA could hybridize with the target DNA, leading to the 5' terminus of the DNA-AuNCs and the 3' terminus of G-rich DNA being in close proximity and promoting the cooperative hybridization. Therefore, a "Y" junction structure was formed and the G-rich sequences were brought close to the AuNCs. Therefore, the fluorescence intensity of the sensing system decreased significantly. Taking advantage of the poly(A) DNA-templated Au nanoclusters and G-rich DNA proximity-induced quenching, the strategy could be extended to determine other biomolecules by designing appropriate sequences of DNA probes.

14.
Acta Pharmaceutica Sinica ; (12): 432-438, 2024.
Artigo em Chinês | WPRIM | ID: wpr-1016641

RESUMO

This study constructed a LHCGR-CRE-luc-HEK293 transgenic cell line according to the activation of the cAMP signaling pathway after recombinant human chorionic gonadotropin binding to the receptor. The biological activity of recombinant human chorionic gonadotropin was assayed using a luciferase assay system. The relative potency of the samples was calculated using four-parameter model. And the method conditions were optimized to validate the specificity, relative accuracy, precision and linearity of the method. The results showed that there was a quantitative potency relationship of human chorinonic gonadotropin (hCG) in the method and it was in accordance with the four-parameter curve. After optimization, the conditions were determined as hCG dilution concentration of 2.5 μg·mL-1, dilution ratio of 1∶4, cell number of 10 000-15 000 cells/well, and induction time of 6 h. The method had good specificity, relative accuracy with relative bias ranging from -8.9% to 3.4%, linear regression equation correlation coefficient of 0.996, intermediate precision geometric coefficient of variation ranging from 3.3% to 15.0%, and linearity range of 50% to 200%. This study successfully established and validated a reporter gene method to detect hCG biological activity, which can be used for hCG biological activity assay and quality control.

15.
J Steroid Biochem Mol Biol ; 111(3-5): 262-7, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18621127

RESUMO

Selective thyroid hormone receptor subtype-beta (TRbeta) agonists have received attention as potential treatments for hypercholesterolemia and obesity, but have received less attention as treatments for diabetes, partly because this condition is not improved in thyroid hormone excess states. The TRbeta selective agonist KB-141 induces 5-10% increases in metabolic rate and lowering of plasma cholesterol levels without tachycardia in lean rats, unlike the major active thyroid hormone, T3. In the current study, we determined whether KB-141 promotes weight loss in obese animals and whether it exhibits anti-diabetogenic effects. Body weight, adiposity (DEXA), and lipid levels were examined following p.o. administration of KB-141 to obese Zucker fa/fa rats at 0.00547-0.547 mg/kg/day for 21 days, and in ob/ob mice at 0.5mg/kg/day KB-141 for 7 days. In rats, KB-141 reduced body weight by 6 and 8%, respectively, at 0.167 and 0.0547 mg/kg/day without tachycardia and adiposity was reduced at 0.167 mg/kg/day (5-6%). In ob/ob mice, KB-141 lowered serum cholesterol (35%), triacylglycerols (35%) and both serum and hepatic free fatty acids (18-20%) without tachycardia. Treatment of ob/ob mice with KB-141 (0.0547 or 0.328 mg/kg/day over 2 weeks) improved glucose tolerance and insulin sensitivity in a dose-dependent manner with no effect on heart rate. Thus, KB-141 elicits anti-obesity, lipid lowering and anti-diabetic effects without tachycardia suggesting that selective TRbeta activation may be useful strategy to attenuate features of the metabolic syndrome.


Assuntos
Fármacos Antiobesidade/uso terapêutico , Diabetes Mellitus/tratamento farmacológico , Hipercolesterolemia/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/uso terapêutico , Obesidade/tratamento farmacológico , Éteres Fenílicos/uso terapêutico , Fenilacetatos/uso terapêutico , Receptores beta dos Hormônios Tireóideos/agonistas , Animais , Fármacos Antiobesidade/química , Fármacos Antiobesidade/farmacologia , Peso Corporal/efeitos dos fármacos , Feminino , Humanos , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Hipolipemiantes/química , Hipolipemiantes/farmacologia , Camundongos , Camundongos Obesos , Estrutura Molecular , Éteres Fenílicos/química , Éteres Fenílicos/farmacologia , Fenilacetatos/química , Fenilacetatos/farmacologia , Ratos , Ratos Zucker
16.
Artigo em Chinês | WPRIM | ID: wpr-971263

RESUMO

Objective: In this study, we aimed to investigate the prevalence of low anterior resection syndrome (LARS) in patients who had survived for more than 5 years after sphincter-preserving surgery for rectal cancer and to analyze its relationship with postoperative time. Methods: This was a single-center, retrospective, cross-sectional study. The study cohort comprised patients who had survived for at least 5 years (60 months) after undergoing sphincter- preserving radical resection of pathologically diagnosed rectal adenocarcinoma within 15 cm of the anal verge in the Department of Gastrointestinal Surgery, Peking University People's Hospital from January 2005 to May 2016. Patients who had undergone local resection, had permanent stomas, recurrent intestinal infection, local recurrence, history of previous anorectal surgery, or long- term preoperative defecation disorders were excluded. A LARS questionnaire was administered by telephone interview, points being allocated for incontinence for flatus (0-7 points), incontinence for liquid stools (0-3 points), frequency of bowel movements (0-5 points), clustering of stools (0-11 points), and urgency (0-16 points). The patients were allocated to three groups based on these scores: no LARS (0-20 points), minor LARS (21-29 points), and major LARS (30-42 points). The prevalence of LARS and major LARS in patients who had survived more than 5 years after surgery, correlation between postoperative time and LARS score, and whether postoperative time was a risk factor for major LARS and LARS symptoms were analyzed. Results: The median follow-up time of the 160 patients who completed the telephone interview was 97 (60-193) months; 81 (50.6%) of them had LARS, comprising 34 (21.3%) with minor LARS and 47 (29.4%) with major LARS. Spearman correlation analysis showed no significant correlation between LARS score and postoperative time (correlation coefficient α=-0.016, P=0.832). Multivariate analysis identified anastomotic height (RR=0.850, P=0.022) and radiotherapy (RR=5.760, P<0.001) as independent risk factors for major LARS; whereas the postoperative time was not a significant risk factor (RR=1.003, P=0.598). The postoperative time was also not associated with LARS score rank and frequency of bowel movements, clustering, or urgency (P>0.05). However, the rates of incontinence for flatus (3/31, P=0.003) and incontinence for liquid stools (8/31, P=0.005) were lower in patients who had survived more than 10 years after surgery. Conclusions: Patients with rectal cancer who have survived more than 5 years after sphincter-preserving surgery still have a high prevalence of LARS. We found no evidence of major LARS symptoms resolving over time.


Assuntos
Humanos , Neoplasias Retais/patologia , Estudos Transversais , Síndrome de Ressecção Anterior Baixa , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Flatulência/complicações , Canal Anal/patologia , Diarreia , Qualidade de Vida
17.
Journal of Forensic Medicine ; (6): 137-143, 2023.
Artigo em Inglês | WPRIM | ID: wpr-981847

RESUMO

OBJECTIVES@#To explore the changes of elbow flexor muscle strength after musculocutaneous nerve injury and its correlation with needle electromyography (nEMG) parameters.@*METHODS@#Thirty cases of elbow flexor weakness caused by unilateral brachial plexus injury (involving musculocutaneous nerve) were collected. The elbow flexor muscle strength was evaluated by manual muscle test (MMT) based on Lovett Scale. All subjects were divided into Group A (grade 1 and grade 2, 16 cases) and Group B (grade 3 and grade 4, 14 cases) according to their elbow flexor muscle strength of injured side. The biceps brachii of the injured side and the healthy side were examined by nEMG. The latency and amplitude of the compound muscle action potential (CMAP) were recorded. The type of recruitment response, the mean number of turns and the mean amplitude of recruitment potential were recorded when the subjects performed maximal voluntary contraction. The quantitative elbow flexor muscle strength was measured by portable microFET 2 Manual Muscle Tester. The percentage of residual elbow flexor muscle strength (the ratio of quantitative muscle strength of the injured side to the healthy side) was calculated. The differences of nEMG parameters, quantitative muscle strength and residual elbow flexor muscle strength between the two groups and between the injured side and the healthy side were compared. The correlation between elbow flexor manual muscle strength classification, quantitative muscle strength and nEMG parameters was analyzed.@*RESULTS@#After musculocutaneous nerve injury, the percentage of residual elbow flexor muscle strength in Group B was 23.43% and that in Group A was 4.13%. Elbow flexor manual muscle strength classification was significantly correlated with the type of recruitment response, and the correlation coefficient was 0.886 (P<0.05). The quantitative elbow flexor muscle strength was correlated with the latency and amplitude of CMAP, the mean number of turns and the mean amplitude of recruitment potential, and the correlation coefficients were -0.528, 0.588, 0.465 and 0.426 (P<0.05), respectively.@*CONCLUSIONS@#The percentage of residual elbow flexor muscle strength can be used as the basis of muscle strength classification, and the comprehensive application of nEMG parameters can be used to infer quantitative elbow flexor muscle strength.


Assuntos
Humanos , Cotovelo , Eletromiografia , Nervo Musculocutâneo , Articulação do Cotovelo/fisiologia , Músculo Esquelético , Força Muscular , Traumatismos dos Nervos Periféricos
18.
Artigo em Chinês | WPRIM | ID: wpr-1008668

RESUMO

This study constructed a nano-drug delivery system, A3@GMH, by co-delivering the stapled anoplin peptide(Ano-3, A3) with the light-harvesting material graphene oxide(GO), and evaluated its oncolytic immunotherapy effect on triple-negative breast cancer(TNBC). A3@GMH was prepared using an emulsion template method and its physicochemical properties were characterized. The in vivo and in vitro photothermal conversion abilities of A3@GMH were investigated using an infrared thermal imager. The oncoly-tic activity of A3@GMH against TNBC 4T1 cells was evaluated through cell counting kit-8(CCK-8), lactate dehydrogenase(LDH) release, live/dead cell staining, and super-resolution microscopy. The targeting properties of A3@GMH on 4T1 cells were assessed using a high-content imaging system and flow cytometry. In vitro and in vivo studies were conducted to investigate the antitumor mechanism of A3@GMH in combination with photothermal therapy(PTT) through inducing immunogenic cell death(ICD) in 4T1 cells. The results showed that the prepared A3@GMH exhibited distinct mesoporous and coated structures with an average particle size of(308.9±7.5) nm and a surface potential of(-6.79±0.58) mV. The encapsulation efficiency and drug loading of A3 were 23.9%±0.6% and 20.5%±0.5%, respectively. A3@GMH demonstrated excellent photothermal conversion ability and biological safety. A3@GMH actively mediated oncolytic features such as 4T1 cell lysis and LDH release, as well as ICD effects, and showed enhanced in vitro antitumor activity when combined with PTT. In vivo, A3@GMH efficiently induced ICD effects with two rounds of PTT, activated the host's antitumor immune response, and effectively suppressed tumor growth in 4T1 tumor-bearing mice, achieving an 88.9% tumor inhibition rate with no apparent toxic side effects. This study suggests that the combination of stapled anoplin peptide and PTT significantly enhances the oncolytic immunotherapy for TNBC and provides a basis for the innovative application of anti-tumor peptides derived from TCM in TNBC treatment.


Assuntos
Humanos , Animais , Camundongos , Terapia Fototérmica , Neoplasias de Mama Triplo Negativas/patologia , Peptídeos Catiônicos Antimicrobianos , Imunoterapia/métodos , Linhagem Celular Tumoral , Fototerapia/métodos , Nanopartículas/química
19.
Mol Cell Biol ; 22(23): 8226-40, 2002 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-12417726

RESUMO

The PEX11 peroxisomal membrane proteins promote peroxisome division in multiple eukaryotes. As part of our effort to understand the molecular and physiological functions of PEX11 proteins, we disrupted the mouse PEX11alpha gene. Overexpression of PEX11alpha is sufficient to promote peroxisome division, and a class of chemicals known as peroxisome proliferating agents (PPAs) induce the expression of PEX11alpha and promote peroxisome division. These observations led to the hypothesis that PPAs induce peroxisome abundance by enhancing PEX11alpha expression. The phenotypes of PEX11alpha(-/-) mice indicate that this hypothesis remains valid for a novel class of PPAs that act independently of peroxisome proliferator-activated receptor alpha (PPARalpha) but is not valid for the classical PPAs that act as activators of PPARalpha. Furthermore, we find that PEX11alpha(-/-) mice have normal peroxisome abundance and that cells lacking both PEX11alpha and PEX11beta, a second mammalian PEX11 gene, have no greater defect in peroxisome abundance than do cells lacking only PEX11beta. Finally, we report the identification of a third mammalian PEX11 gene, PEX11gamma, and show that it too encodes a peroxisomal protein.


Assuntos
Proteínas de Membrana/genética , Proliferadores de Peroxissomos/farmacologia , Peroxissomos/efeitos dos fármacos , Peroxissomos/metabolismo , Fenilbutiratos/farmacologia , Receptores Citoplasmáticos e Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Sequência de Aminoácidos , Animais , Antineoplásicos/farmacologia , Dieta , Ácidos Graxos/química , Ácidos Graxos/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Marcação de Genes , Fígado/citologia , Fígado/metabolismo , Proteínas de Membrana/química , Proteínas de Membrana/classificação , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos , Camundongos Knockout , Mitocôndrias/ultraestrutura , Dados de Sequência Molecular , Oxirredução , Proliferadores de Peroxissomos/administração & dosagem , Peroxissomos/ultraestrutura , Fenótipo , Filogenia , Plasmalogênios/metabolismo , Alinhamento de Sequência , Distribuição Tecidual
20.
Journal of Clinical Hepatology ; (12): 515-520, 2022.
Artigo em Chinês | WPRIM | ID: wpr-922944

RESUMO

Hepatobiliary tumor is a type of malignant tumor including primary liver cancer, cholangiocarcinoma, and gallbladder carcinoma. At present, hepatobiliary tumors have become the second leading cause of cancer-related death worldwide, while the treatment methods for such tumors cannot effectively meet clinical needs. Therefore, it is a key scientific problem in this field to explore and develop the experimental technology of accurate drug screening for hepatobiliary tumors, find new strategies and methods for clinical treatment, and provide new ideas for early diagnosis and comprehensive treatment of hepatobiliary tumors. This article introduces the latest research advances in the novel technologies for accurate drug screening for hepatobiliary tumor and their application potential by focusing on the construction of individualized pathological models of hepatobiliary tumor, drug screening technologies, the design and screening strategy of specific target drugs, and drug screening strategy based on artificial intelligence and big data analysis, as well as the directions for future development.

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