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1.
J Am Chem Soc ; 2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38607333

RESUMO

Unraveling the mechanism of chirality transfer across length scales is crucial to the rational development of functional materials with hierarchical chirality. The key obstacle is the lack of structural information, especially at the mesoscopic level. We report herein the structural identification of helical covalent organic frameworks (heliCOFs) with hierarchical chirality, which integrate molecular chirality, channel chirality, and morphology chirality into one crystalline entity. Specifically, benefiting from the highly ordered structure of heliCOFs, the existence of chiral channels at the mesoscopic level has been confirmed by electron crystallography, and the handedness of these chiral channels has been directly determined through the stereopair imaging technique. Accordingly, the chirality transfer in heliCOFs from microscopic to macroscopic levels could be rationalized with a layer-rotating model that has been supported by both crystal structure analysis and theoretical calculations. Observation of chiral channels in heliCOFs not only provides unprecedented data for the understanding of the chirality transfer process but also sheds new light on the rational construction of highly ordered polymeric materials with hierarchical chirality.

2.
Eur J Haematol ; 113(3): 357-370, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38847134

RESUMO

BACKGROUND: IKZF1 deletion (IKZF1del) is associated with poor prognosis in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). But the prognosis of IKZF1del combined with other prognostic stratification factors remains unclear. Whether intensified treatment improves BCP-ALL prognosis has not been determined. METHODS: A retrospective analysis was performed on 1291 pediatric patients diagnosed with BCP-ALL and treated with the South China Children's Leukemia 2016 protocol. Patients were stratified based on IKZF1 status for comparison of characteristics and outcome. Additionally, IKZF1del patients were further divided based on chemotherapy intensity for outcome assessments. RESULTS: The BCP-ALL pediatric patients with IKZF1del in south China showed poorer early response. Notably, the DFS and OS for IKZF1del patients were markedly lower than IKZF1wt group (3-year DFS: 88.7% [95% CI: 83.4%-94.0%] vs. 93.5% [95% CI: 92.0%-94.9%], P = .021; 3-year OS: 90.7% [95% CI: 85.8% to 95.6%] vs. 96.1% [95% CI: 95% to 97.2%, P = .003]), with a concurrent increase in 3-year TRM (6.4% [95% CI: 2.3%-10.5%] vs. 2.9% [95% CI: 1.9%-3.8%], P = .025). However, the 3-year CIR was comparable between the two groups (5.7% [95% CI: 1.8%-9.5%] vs. 3.7% [95% CI: 2.6%-4.7%], P = .138). Subgroup analyses reveal no factor significantly influenced the prognosis of the IKZF1del cohort. Noteworthy, intensive chemotherapy improved DFS from 85.7% ± 4.1% to 94.1% ± 0.7% in IKZF1del group (P = .084). Particularly in BCR::ABL positive subgroup, the 3-year DFS was remarkably improved from 53.6% ± 20.1% with non-intensive chemotherapy to 100% with intensive chemotherapy (P = .026). CONCLUSIONS: Pediatric BCP-ALL patients with IKZF1del in South China manifest poor outcomes without independent prognostic significance. While no factor substantially alters the prognosis in the IKZF1del group. Intensified chemotherapy may reduce relapse rates and improve DFS in patients with IKZF1del subset, particularly in IKZFdel patients with BCR::ABL positive.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Fator de Transcrição Ikaros , Leucemia-Linfoma Linfoblástico de Células Precursoras B , Humanos , Fator de Transcrição Ikaros/genética , Masculino , Feminino , Prognóstico , Criança , Pré-Escolar , Estudos Retrospectivos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras B/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/mortalidade , Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Lactente , Adolescente , Resultado do Tratamento , Deleção de Genes , China/epidemiologia
3.
Postgrad Med J ; 100(1184): 373-381, 2024 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-38211949

RESUMO

In recent years, immunotherapy strategies based on immune checkpoint inhibitors have yielded good efficacy in colorectal cancer (CRC)especially in colorectal cancer with microsatellite instability-high. However, microsatellite-stable (MSS) CRCs account for about 85% of CRCs and are resistant to immunotherapy. Previous studies have shown that compared with MSS CRC, high microsatellite instability CRC possesses a higher frequency of mutations and can generate more neoantigens. Therefore, improving the sensitivity of immunotherapy to MSS CRC is a hot topic which is crucial for the treatment of MSS CRC. This review aims to discuss the factors contributing to MSS CRC insensitivity to immunotherapy and explored potential solutions to overcome immunotherapy resistance.


Assuntos
Neoplasias Colorretais , Inibidores de Checkpoint Imunológico , Imunoterapia , Instabilidade de Microssatélites , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/terapia , Neoplasias Colorretais/imunologia , Imunoterapia/métodos , Inibidores de Checkpoint Imunológico/uso terapêutico , Resistencia a Medicamentos Antineoplásicos/genética , Mutação
4.
Zhongguo Zhong Yao Za Zhi ; 49(3): 779-788, 2024 Feb.
Artigo em Zh | MEDLINE | ID: mdl-38621882

RESUMO

This study aims to investigate the essential oil(EOL) of Cinnamomum camphora regarding its anti-depression effect and mechanism in regulating inflammatory cytokines and the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1) pathway. A mouse model of depression was established by intraperitoneal injection of lipopolysaccharide(LPS). Open field, elevated plus maze, and forced swimming tests were carried out to examine mouse behaviors. Western blot and qRT-PCR were employed to determine the expression of proteins and genes in the Nrf2/HO-1 pathway in the hippocampus. The levels of tumor necrosis factor(TNF)-α, interleukin(IL)-6, and IL-1ß in the serum were measured by enzyme-linked immunosorbent assay(ELISA). The changes of apoptosis in mouse brain were detected by Tunel staining. Compared with the blank control group, the model group showed shortened distance travelled and time spent in the central zone and reduced number of entries in the central zone in the open field test. In the elevated plus maze test, the model group showed reduced open arm time(OT%) and open arm entries(OE%). In the force swimming test, the model group showed extended duration of immobility compared with the blank control group. Compared with the model group, the treatment with EOL significantly increased the distance travelled and time spent in the central zone and increased the number of entries in the central zone in the open field test. In addition, EOL significantly increased the OT% and OE% in the elevated plus maze and shor-tened the immobility duration in the forced swimming test. The model group showed lower expression levels of Nrf2 and HO-1 and hig-her levels of TNF-α, IL-6, and IL-1ß than the blank control group. Compared with the model group, the treatment with EOL up-regulated the expression levels of Nrf2 and HO-1 and lowered the levels of TNF-α, IL-6, and IL-1ß. The Tunel staining results showed that the apoptosis rate in the brain tissue of mice decreased significantly after the treatment with EOL. To sum up, EOL can mitigate the depression-like behaviors of mice by up-regulating the expression of Nrf2 and HO-1 and preventing hippocampal inflammatory damage. The findings provide empirical support for the application of EOL and aromatherapy in the treatment of depression.


Assuntos
Cinnamomum camphora , Óleos Voláteis , Feminino , Camundongos , Animais , Citocinas/metabolismo , Fator de Necrose Tumoral alfa , Interleucina-6 , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Depressão/tratamento farmacológico , Óleos Voláteis/farmacologia , Lipopolissacarídeos/farmacologia
5.
J Am Chem Soc ; 144(14): 6594-6603, 2022 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-35380432

RESUMO

The development of linkage chemistry in the research area of covalent organic frameworks (COFs) is fundamentally important for creating robust structures with high crystallinity and diversified functionality. We reach herein a new level of complexity and controllability in linkage chemistry by achieving the first synthesis of fused-ring-linked COFs. A series of bicyclic pyrano[4,3-b]pyridine COFs have been constructed via a cascade protocol involving Schiff-base condensation, intramolecular [4 + 2] cycloaddition, and dehydroaromatization. With a broad scope of Brønsted or Lewis acids as the catalyst, the designed monomers, that is, O-propargylic salicylaldehydes and multitopic anilines, were converted into the fused-ring-linked frameworks in a one-pot fashion. The obtained COFs exhibited excellence in terms of purity, stability, and crystallinity, as comprehensively characterized by solid-state nuclear magnetic resonance (NMR) spectroscopy, powder X-ray diffraction, high-resolution transmission electron microscopy, and so on. Specifically, the highly selective formation (>94%) of pyrano[4,3-b]pyridine linkage was verified by quantitative NMR measurements combined with 13C-labeling synthesis. Moreover, the fused-ring linkage possesses fully locked conformation, which benefits to the high crystallinity observed for these COFs. Advancing the linkage chemistry from the formation of solo bonds or single rings to that of fused rings, this study has opened up new possibilities for the concise construction of sophisticated COF structures with high controllability.


Assuntos
Estruturas Metalorgânicas , Catálise , Espectroscopia de Ressonância Magnética , Estruturas Metalorgânicas/química , Difração de Raios X
6.
Anal Chem ; 92(24): 15699-15704, 2020 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-33263986

RESUMO

Real-time and rapid detection of various biomarkers in body fluids has important significance for early disease diagnosis, efficient monitoring of treatment, and evaluation of prognosis. However, traditional detection methods not only require bulky and costly instruments but also are not suitable for the analysis of heterogeneous samples (e.g., serum and urine), limiting their applications in point-of-care testing (POCT). Herein, an integrated photoacoustic (PA) device with a smartphone as the acoustic signal readout has been constructed, greatly reducing the volume and cost of the instrument, and providing a potential miniature platform for POCT of clinical samples. By exploiting the electron transfer product of 3,3',5,5'-tetramethylbenzidine (TMB) (i.e., TMB++) as the PA probe and hemin-graphene oxide (H-GO) complex as the peroxidase, quantitative analysis of uric acid was successfully performed by using only 30 µL of a sample solution. Due to the favorable stability of artificial enzymes, reaction reagents could be effectively embedded in agar gel to make a portable "test strip". Therefore, operators just need to drop clinical samples on the "test strip" for PA analysis, which is user friendly without requiring complex sample preparation steps. In addition, since the acoustic change mainly comes from the PA effect, it has a lower background signal than UV-vis and fluorescence analysis, greatly improving the analytical performance. The simplicity, low cost, and broad adaptability make this miniature PA device attractive for on-site detection, particularly in resource-limited settings.


Assuntos
Técnicas Biossensoriais , Técnicas Fotoacústicas , Testes Imediatos , Smartphone , Ácido Úrico/análise , Humanos
7.
Anal Chem ; 92(21): 14806-14813, 2020 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-33058681

RESUMO

Butyrylcholinesterase (BuChE), the primary source of serum cholinesterase activity, is an indispensable biochemical marker for clinical diagnosis of liver function and organophosphorus poisoning. The requirement for bulky and expensive instruments represents a huge hindrance for point-of-care testing (POCT) of BuChE, especially in resource-limited settings. Herein, an easy-operated, economic, and portable photothermal (PT) biosensing platform for high-throughput BuChE detection was rationally designed. BuChE could "light up" the PT signal through in situ generation of Prussian blue (PB) by MIL-53 (Fe), which allowed us to translate biological signals into temperature signals. Such temperature change signals could be monitored at high throughput (six samples for a single measurement) by a miniature self-made integrated PT device via combining separable 96-well plates, a three-dimensional (3D) printed sample bracket, 808 nm lasers, and thermometers, satisfying the requirement for rapid on-site detection in a large batch with low cost. In addition, the large specific surface area, 3D network structure, and high porosity of MIL-53 (Fe) offered a beneficial platform for its reaction with enzymatic hydrolysate, resulting in high sensing sensitivity and low detection limit (0.3 U L-1), which was at least 20 000 times lower than the normal human serum BuChE activity. This facile, affordable, and broad applicability PT sensing platform provides a beneficial reference for the rational design of other disease diagnostic approaches suitable for POCT.


Assuntos
Técnicas Biossensoriais/instrumentação , Butirilcolinesterase/metabolismo , Ferrocianetos/química , Ferro/química , Compostos Organometálicos/química , Testes Imediatos , Temperatura , Butirilcolinesterase/sangue , Humanos , Limite de Detecção
8.
Int J Syst Evol Microbiol ; 70(7): 4179-4185, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32558636

RESUMO

A novel moderately halophilic, filamentous actinobacterium, designated as XMNu-373T, was isolated from a saline-alkaline soil sample collected from the Mongolia Plateau, Dongwu County, Inner Mongolia Autonomous Region, PR China. The isolate grew optimally at 28‒37 °C, pH 7.0‒8.0 and with 2-5 % (w/v) NaCl. The substrate mycelia fragmented into rod-like elements, and the white aerial mycelia formed spore chains at maturity. The predominant menaquinone was MK-9(H4). The polar lipids were diphosphatidylglycerol, three unidentified phosphoglycolipids, an unidentified aminophospholipid, two phosphatidylinositol mannosides, four unidentified phospholipids, phosphatidylglycerol and two unidentified lipids. The major cellular fatty acids were iso-C16 : 0, anteiso-C17 : 0 and anteiso-C15 : 0. The genomic DNA G+C content was 66.2 mol%. It shared high 16S rRNA gene sequence similarities to Phytoactinopolyspora halotolerans YIM 96448T (96.1 %) and Phytoactinopolyspora endophytica EGI 60009T (96.0 %). Phylogenetic trees based on 16S rRNA gene sequences revealed that strain XMNu-373T resided in the clade of family Jiangellaceae, and it formed a monophyletic branch distinct from four other recognized type species in the subclade of the genus Phytoactinopolyspora. On the basis of polyphasic taxonomic evidence, strain XMNu-373T represents a novel species of the genus Phytoactinopolyspora, for which the name Phytoactinopolyspora mesophila sp. nov. is proposed. The type strain is XMNu-373T (=JCM 33740T=CGMCC 4.7654T).


Assuntos
Actinobacteria/classificação , Álcalis , Filogenia , Salinidade , Microbiologia do Solo , Actinobacteria/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Solo/química , Vitamina K 2/análogos & derivados , Vitamina K 2/química
9.
J Integr Plant Biol ; 62(11): 1653-1658, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32396228

RESUMO

Cas12b/C2c1 is a newly identified class 2 CRISPR endonuclease that was recently engineered for targeted genome editing in mammals and rice. To explore the potential applications of the CRISPR-Cas12b system in the dicot Arabidopsis thaliana, we selected BvCas12b and BhCas12b v4 for analysis. We successfully used both endonucleases to induce mutations, perform multiplex genome editing, and create large deletions at multiple loci. No significant mutations were detected at potential off-target sites. Analysis of the insertion/deletion frequencies and patterns of mutants generated via targeted gene mutagenesis highlighted the potential utility of CRISPR-Cas12b systems for genome editing in Arabidopsis.


Assuntos
Arabidopsis/metabolismo , Genoma de Planta/genética , Arabidopsis/genética , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Sistemas CRISPR-Cas/genética , Edição de Genes , Mutagênese , Mutação/genética
10.
Arch Toxicol ; 93(2): 547-558, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30377736

RESUMO

Triclosan (TCS), as a broad spectrum antibacterial agent, is commonly utilized in personal care and household products. Maternal urinary TCS level has been associated with changes in birth weight of infants. We in the present study investigated whether exposure of mice to 8 mg/kg TCS from gestational day (GD) 6 to GD14 alters prenatal and postnatal growth and development, and metabolic phenotypes in male and female offspring (TCS-offspring). Compared with control offspring, body weight in postnatal day (PND) 1 male or female TCS-offspring was reduced, but body weight gain was faster within postnatal 5 days. PND30 and PND60 TCS-offspring showed overweight with increases in visceral fat and adipocyte size. PND60 TCS-offspring displayed delayed glucose clearance and insulin resistance. PND30 TCS-offspring showed an increase in food intake without the changes in the oxygen consumption and respiratory exchange ratio (RER). The expression levels of proopiomelanocortin (POMC), α-melanocyte-stimulating hormone (α-MSH) and single-minded 1 (SIM1) in hypothalamus arcuate nucleus (ARC) and paraventricular nucleus (PVN), respectively, were significantly reduced in PND30 TCS-offspring compared to controls. The hypermethylation of CpG sites at the POMC promoter was observed in PND30 TCS-offspring, while the concentration of serum leptin was elevated and the level of STAT3 phosphorylation in ARC had no significant difference from control. This study demonstrates that TCS exposure during early/mid-gestation through the hypermethylation of the POMC promoter reduces the expression of anorexigenic neuropeptides to cause the postnatal hyperphagic obesity, leading to metabolic syndrome in adulthood.


Assuntos
Hiperfagia/complicações , Obesidade/etiologia , Efeitos Tardios da Exposição Pré-Natal , Pró-Opiomelanocortina/genética , Triclosan/toxicidade , Animais , Núcleo Arqueado do Hipotálamo/efeitos dos fármacos , Núcleo Arqueado do Hipotálamo/fisiologia , Metilação de DNA/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Hiperfagia/induzido quimicamente , Hiperfagia/genética , Resistência à Insulina , Masculino , Obesidade/genética , Gravidez , Pró-Opiomelanocortina/metabolismo , Regiões Promotoras Genéticas , Aumento de Peso/efeitos dos fármacos , alfa-MSH/biossíntese
11.
J Acoust Soc Am ; 144(1): 478, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-30075670

RESUMO

This paper investigates the methods to detect and classify marmoset vocalizations automatically using a large data set of marmoset vocalizations and deep learning techniques. For vocalization detection, neural networks-based methods, including deep neural network (DNN) and recurrent neural network with long short-term memory units, are designed and compared against a conventional rule-based detection method. For vocalization classification, three different classification algorithms are compared, including a support vector machine (SVM), DNN, and long short-term memory recurrent neural networks (LSTM-RNNs). A 1500-min audio data set containing recordings from four pairs of marmoset twins and manual annotations is employed for experiments. Two test sets are built according to whether the test samples are produced by the marmosets in the training set (test set I) or not (test set II). Experimental results show that the LSTM-RNN-based detection method outperformed others and achieved 0.92% and 1.67% frame error rate on these two test sets. Furthermore, the deep learning models obtained higher classification accuracy than the SVM model, which was 95.60% and 91.67% on the two test sets, respectively.


Assuntos
Algoritmos , Aprendizado Profundo , Memória de Longo Prazo/fisiologia , Redes Neurais de Computação , Animais , Callithrix/fisiologia , Máquina de Vetores de Suporte
12.
Anal Chem ; 88(8): 4192-5, 2016 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-27030025

RESUMO

The low atomization and excitation capability of nonthermal microplasma, e.g., dielectric barrier discharge (DBD), has greatly hampered its potential applications for the determination of metals in solution. In the present work, an inspiring development is reported for direct atomization and excitation of cadmium in aqueous solution by DBD and facilitates highly sensitive determination. A DBD microplasma is generated on the nozzle of a pneumatic micronebulizer to focus the DBD energy on a confined space and atomize/excite metals in the spray. Meanwhile, an appropriate sample matrix and nebulization in helium further improves the atomization and excitation capability of DBD. With cadmium as a model, its emission is recorded by a CCD spectrometer at 228.8 nm. By using an 80 µL sample solution nebulized at 3 µL s(-1), a linear range of 5-1000 µg L(-1) along with a detection limit of 1.5 µg L(-1) is achieved, which is comparable to those obtained by commercial bulky inductively coupled plasma (ICP)-based instrumentations.


Assuntos
Cádmio/análise , Cádmio/química , Espectrofotometria Atômica/instrumentação
13.
Gynecol Obstet Invest ; 81(3): 220-4, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26461523

RESUMO

AIMS: This study aims to explore the independent predictors of gestational diabetes mellitus (GDM) in Chinese women with polycystic ovary syndrome (PCOS). METHODS: This cross-sectional study analyzed primigravid women with PCOS and classified them as those with and without GDM. Independent risk factors and model performance were analyzed using multivariate logistic regression and the area under the curve (AUC) of receiver operating characteristic (ROC), respectively. RESULTS: Maternal body mass index, waist circumference, waist-to-hip ratio (WHR), fasting glucose, insulin, sex hormone-binding globulin (SHBG), homeostasis model assessment-insulin resistance (HOMA-IR) before pregnancy, gestation weight gain before 24 weeks and the incidence of family history of diabetes were different in the 2 groups. Logistic regression analysis showed that pre-pregnancy WHR, SHBG, HOMA-IR and gestation weight gain before 24 weeks were the independent predictors of GDM. ROC curve analysis confirmed that gestation weight gain before 24 weeks (AUC 0.767, 95% CI 0.688-0.841), pre-pregnant WHR (AUC 0.725, 95% CI 0.649-0.802), HOMA-IR (AUC 0.711, 95% CI 0.632-0.790) and SHBG levels (AUC 0.709, 95% CI 0.625-0.793) were the strong risk factors. CONCLUSIONS: In Chinese women with PCOS, factors of gestation weight gain before 24 weeks, pre-pregnant WHR, HOMA-IR and SHBG levels are strongly associated with subsequent development of GDM.


Assuntos
Glicemia/análise , Diabetes Gestacional/diagnóstico , Síndrome do Ovário Policístico/complicações , Adulto , Área Sob a Curva , Índice de Massa Corporal , China , Estudos Transversais , Diabetes Gestacional/fisiopatologia , Feminino , Idade Gestacional , Humanos , Insulina/sangue , Resistência à Insulina , Modelos Logísticos , Síndrome do Ovário Policístico/fisiopatologia , Gravidez , Curva ROC , Fatores de Risco , Globulina de Ligação a Hormônio Sexual , Circunferência da Cintura , Relação Cintura-Quadril , Aumento de Peso
14.
Molecules ; 21(8)2016 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-27517893

RESUMO

Oxidative stress plays an important role in the pathogenesis of cardiovascular diseases. Salidroside (SAL), one of the main effective constituents of Rhodiola rosea, has been reported to suppress oxidative stress-induced cardiomyocyte injury and necrosis by promoting transcription of nuclear factor E2-related factor 2 (Nrf2)-regulated genes such as heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase (quinone1) (NQO1). However, it has not been indicated whether SAL might ameliorate endothelial injury induced by oxidative stress. Here, our study demonstrated that SAL might suppress HUVEC cell injury induced by oxidative stress through activating the Nrf2 signaling pathway. The results of our study indicated that SAL decreased the levels of intercellular reactive oxygen species (ROS) and malondialdehyde (MDA), and improved the activities of superoxide dismutase (SOD) and catalase (CAT), resulting in protective effects against oxidative stress-induced cell damage in HUVECs. It suppressed oxidative stress damage by inducing Nrf2 nuclear translocation and activating the expression of Nrf2-regulated antioxidant enzyme genes such as HO-1 and NQO1 in HUVECs. Knockdown of Nrf2 with siRNA abolished the cytoprotective effects against oxidative stress, decreased the expression of Nrf2, HO-1, and NQO1, and inhibited the nucleus translocation of Nrf2 in HUVECs. This study is the first to demonstrate that SAL suppresses HUVECs cell injury induced by oxidative stress through activating the Nrf2 signaling pathway.


Assuntos
Glucosídeos/farmacologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fenóis/farmacologia , Transdução de Sinais/efeitos dos fármacos , Catalase/biossíntese , Heme Oxigenase-1/biossíntese , Células Endoteliais da Veia Umbilical Humana/patologia , Malondialdeído/metabolismo , NAD(P)H Desidrogenase (Quinona)/biossíntese , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/biossíntese
15.
Cryobiology ; 71(1): 135-40, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25956417

RESUMO

The aim of this study was to investigate the effects of L-carnitine (LC) on follicular survival and ovarian function following cryopreservation-thawing and autotransplantation of ovarian tissues. ICR mice were divided into three groups: control; saline group (cryopreservation+autograft+saline); and LC group (cryopreservation+autograft+L-carnitine). The ovarian tissues from control group, saline group, and LC group were histological assessed. There were no significant differences in the percentage of morphologically normal primordial follicles between the LC group and the saline group. After 28 days of autotransplantation, apoptosis rates, plasma malondialdehyde (MDA), progesterone (P4) and estradiol (E2) concentrations, and follicular densities of grafts were evaluated. Apoptosis rate and the concentration of MDA in the LC group were significantly lower than those in the saline group. The concentration of E2 and follicular densities of grafts in LC group were significantly higher than that in saline group. LC inhibits follicle apoptosis and increases follicular survival and function of ovarian graft.


Assuntos
Apoptose/efeitos dos fármacos , Carnitina/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/transplante , Animais , Criopreservação/métodos , Estradiol/sangue , Feminino , Malondialdeído/sangue , Camundongos , Camundongos Endogâmicos ICR , Progesterona/sangue , Distribuição Aleatória , Preservação de Tecido/métodos , Transplante Autólogo , Vitrificação
16.
Cryobiology ; 70(1): 48-52, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25499542

RESUMO

The aim of this study is to determine the link between oocyte cryopreservation and endoplasmic reticulum (ER) stress; whether ER stress inhibition improves the efficiency of oocyte vitrification is also explored. Oocytes from mice were exposure to tauroursodeoxycholic acid (TUDCA, an ER stress inhibitor) or TM (tunicamycin, an ER stress inducer) with or without vitrification. The expressions of X-box binding protein-1 (XBP-1) protein and caspase-12 protein, viability of vitrified-warmed oocytes, and their subsequent embryo competence were measured. The levels of XBP-1 protein and caspase-12 protein expression in vitrified-warmed oocytes were significantly higher than those of fresh control oocytes. TUDCA improved the viability of vitrified-warmed oocytes and their subsequent embryo competence. Mouse oocyte cryopreservation is associated with ER stress, and ER stress inhibition improves the efficiency of oocyte vitrification.


Assuntos
Criopreservação/métodos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Oócitos/fisiologia , Ácido Tauroquenodesoxicólico/farmacologia , Tunicamicina/farmacologia , Animais , Caspase 12/biossíntese , Sobrevivência Celular , Proteínas de Ligação a DNA/biossíntese , Feminino , Camundongos , Camundongos Endogâmicos ICR , Fatores de Transcrição de Fator Regulador X , Fatores de Transcrição/biossíntese , Vitrificação , Proteína 1 de Ligação a X-Box
17.
Surg Endosc ; 27(2): 518-24, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-22806529

RESUMO

BACKGROUND: This study was designed to evaluate the feasibility and safety of total laparoscopic sigmoid and rectal surgery without abdominal incision in combination with transanal endoscopic microsurgery (TEM). METHODS: From May 2010 to October 2011, 34 patients with colon and rectal tumors were treated by total laparoscopic surgery without abdominal incision, and the clinical data of these patients were reviewed. RESULTS: All operations could be successfully accomplished without conversion to open surgery. No diverting ileostomy was created. The average operative time was 151.60 (range, 125-185) minutes. The average blood loss was 200.20 (range, 55-450) ml. All resection margins were negative. Six patients developed postoperative anastomotic leakage. There were no reports of other complications in all patients. CONCLUSIONS: This preliminary study indicated that total laparoscopic sigmoid and rectal surgery in combination with TEM was a safe, feasible, and minimally invasive technique. This advanced surgical technique was developed by combining laparoscopy with the concept of natural orifice transluminal endoscopic surgery.


Assuntos
Colo Sigmoide/cirurgia , Neoplasias Colorretais/cirurgia , Laparoscopia , Microcirurgia/métodos , Cirurgia Endoscópica por Orifício Natural , Reto/cirurgia , Adulto , Idoso , Canal Anal , China , Estudos de Viabilidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Zhonghua Gan Zang Bing Za Zhi ; 21(7): 537-42, 2013 Jul.
Artigo em Zh | MEDLINE | ID: mdl-24074715

RESUMO

OBJECTIVE: To investigate the role of the non-canonical Wnt signaling pathway in development of non-alcoholic steatohepatitis (NASH) related to type 2 diabetes mellitus (T2DM) using a rat model. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into two equal groups: control group, fed a stand diet; T2DM-NASH model group, fed a high sucrose and fat diet for 4 weeks and intraperitoneally injected with streptozotocin (30 mg/kg). Twelve weeks after model establishment, all rats were sacrificed. Serum levels of glucose, alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by biochemical analysis. Liver pathological changes were assessed microscopically by hematoxylin-eosin and oil red O staining. The liver expression of Wnt5a and NF-kB p65 were detected by immunohistochemistry and western blotting (protein), and quantitative real-time PCR (mRNA). RESULTS: The T2DM-NASH model group showed significantly higher levels of glucose (control group: 6.25 +/- 1.28 vs. 31.21 +/- 0.86 mmol/L, t = -36.204, P less than 0.01), ALT (31.00 +/- 3.69 vs. 301.50 +/- 8.62 U/L, t = -99.94, P less than 0.01), and AST (77.58 +/- 1.83 vs. 344.75 +/- 1.82 U/L, t = -358.85, P less than 0.01). The T2DM-NASH group also showed remarkable signs of steatosis and inflammation in hepatic tissues. The T2DM-NASH group had significantly higher integral optical density (IOD) detection of Wnt5a (control group: 1.15E4 +/- 577.45 vs. 4.04E5 +/- 2.42E4, t = -56.24, P less than 0.01) and NF-kB p65 (1.28E4 +/- 1.59E3 vs. 4.21E5 +/- 1.68E4, t = -83.895, P less than 0.01), as well as protein levels detected by western blot (Wnt5a: 4.21 +/- 0.34 vs. 1.00 +/- 0.25, t = 17.030, P less than 0.01; NF-kB p65: 4.93 +/- 0.76 vs. 1 +/- 0.13, t = 11.438, P less than 0.01). The hepatic mRNA levels followed the same trend (Wnt5a: 9.53 +/- 0.64 vs. 1.04 +/- 0.35, t = 20.165, P less than 0.01; NF-kB p65: 0.60 +/- 0.13 vs. 0.74 +/- 0.10, t = -1.802, P = 0.125). In the T2DM-NASH group, hepatic Wnt5a protein expression was positively correlated with ALT (r = 0.64, P less than 0.05), AST (r = 0.59, P less than 0.05), and NF-kB p65 protein expression (r = 0.58, P less than 0.05). CONCLUSION: Wnt5a may activate NF-kB to stimulate an inflammatory response leading to development of NASH related to T2DM.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Fator de Transcrição RelA/metabolismo , Proteínas Wnt/metabolismo , Via de Sinalização Wnt , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Tipo 2/complicações , Fígado/patologia , Masculino , Hepatopatia Gordurosa não Alcoólica/etiologia , Ratos , Ratos Sprague-Dawley , Proteína Wnt-5a
19.
Hepatogastroenterology ; 59(120): 2490-3, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22534545

RESUMO

BACKGROUND/AIMS: To compare the operative range,safety and therapeutic effect of local resection of rectal tumors by using transanal endoscopic microsurgery and conventional transanal excision. METHODOLOGY: We reviewed data from 76 patients treated using conventional TAE during the period from January 2003 to July 2006 and 53 patients treated using TEM during the period from September 2006 to February 2010 in the Ruijin Hospital affiliated with the Shanghai Jiaotong University School of Medicine. RESULTS: Age, gender, tumor size, blood loss and postoperative hospital stay were similar in the 2 groups. The median distance from the anal verge was significantly higher in the TEM group than in the TAE group. Operation time was significantly longer in the TEM group than in the TAE group.During the median follow-up of 40 months, the LRR in the TEM group was lower than that in the TAE group,especially for tumors that are larger (>3cm) and located higher (>8cm from the anal verge) and pT1 carcinomas. CONCLUSIONS: TEM is a safe, effective and minimally invasive surgical technique for the treatment of early rectal neoplasms. Compared to conventional TAE,TEM has a broader operative range and a better therapeutic effect.


Assuntos
Adenoma/cirurgia , Tumor Carcinoide/cirurgia , Carcinoma/cirurgia , Procedimentos Cirúrgicos do Sistema Digestório , Endoscopia , Microcirurgia , Neoplasias Retais/cirurgia , Adenoma/patologia , Tumor Carcinoide/patologia , Carcinoma/patologia , China , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Endoscopia/efeitos adversos , Feminino , Humanos , Estimativa de Kaplan-Meier , Tempo de Internação , Masculino , Microcirurgia/efeitos adversos , Pessoa de Meia-Idade , Análise Multivariada , Hemorragia Pós-Operatória/etiologia , Modelos de Riscos Proporcionais , Neoplasias Retais/patologia , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Carga Tumoral
20.
Acta Crystallogr Sect E Struct Rep Online ; 68(Pt 6): o1763-4, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22719546

RESUMO

The asymmetric unit in the title compound, C(33)H(34)N(2)O(2)·H(2)O, consists of a V-shaped mol-ecule and a water mol-ecule to which it is hydrogen bonded. The angle between the mean planes of the two spiro-connected indane groups is 77.06 (5)°. The two five-membered rings of the indane groups have envelope conformations with the methyl-ene atoms adjacent to the spiro C atom forming the flaps. They have deviations from the mean plane of the other four atoms in the rings of 0.374 (4) and 0.362 (4) Å. In the crystal, molecules are linked to form inversion dimers via O-H⋯N hydrogen bonds involving the pyridine N atoms and the solvent water mol-ecule. The dimers are linked into a chain along the b axis by π-π stacking inter-actions between a pyridine ring and its centrosymmetrically related ring in an adjacent dimer. The centroid-centroid distance between the planes is 3.7756 (17) Å, the perpendicular distance is 3.4478 (11) Šand the offset is 1.539 Å.

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