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1.
Cell Tissue Bank ; 23(3): 459-472, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34494222

RESUMO

Neural progenitor cells (NPCs) transplantation is known as a potential strategy for treating spinal cord injury (SCI). This study aimed to investigate effects of insulin growth factor-1 (IGF-I) on NPCs proliferation and clarify associated mechanisms. NPCs isolated from T8-T10 segmental spinal cord tissues of rats were cultured and identification. Then, lentivirus packing plasmids containing IGF-I was constructed and used for NPCs infection. Cell proliferation was evaluated by detecting 5-Bromodeoxyuridine (BrdU) expression in NPCs, cell differentiation was detected using double-labeling immunofluorescence staining while cell apoptosis was detected using TUNEL assay. In addition, the signal expression of Akt/mTOR/p70S6K in NPCs cells were investigated using immunofluorescence staining and western blot assay. The experimental group was defined as pCMV-IGF-I group, while the negative control group was defined as pCMV-LacZ group. Cells infected with pCMV-IGF-I lentivirus followed by addition of 100 mg/ml rapamycin were defined as pCMV-IGF-I + Rapa group. NPCs were successfully isolated, identified and cultured. IGF-I overexpression significantly inhibited cell apoptosis and enhanced cell migration. Akt/mTOR/ p70S6K signaling cascade was proved to be present in NPCs, IGF-I overexpression significantly activated Akt/mTOR/p70S6K signaling cascade, while rapamycin addition inhibited its expression. Also, the activated Akt/mTOR/p70S6K signal cascade induced by IGF-I significantly enhanced BrdU expression and inhibited cell apoptosis, and promoted the differentiation of NPC into the neuronal system. However, the rapamycin addition inhibited the cell response induced by IGF-I overexpression. IGF-I overexpression could enhance cell proliferation, inhibit cell apoptosis and promote their differentiation into neuronal systems by activating Akt/mTOR/p70S6K signaling cascade in vitro, indicating that the Akt/mTOR/p70S6K signaling cascade may be the potentially mechanism for the endogenous repair and remodeling of spinal cord after injury.


Assuntos
Células-Tronco Neurais , Proteínas Quinases S6 Ribossômicas 70-kDa , Animais , Apoptose , Bromodesoxiuridina/metabolismo , Bromodesoxiuridina/farmacologia , Proliferação de Células , Insulina , Fator de Crescimento Insulin-Like I/metabolismo , Fator de Crescimento Insulin-Like I/farmacologia , Células-Tronco Neurais/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/farmacologia , Ratos , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Proteínas Quinases S6 Ribossômicas 70-kDa/farmacologia , Transdução de Sinais , Sirolimo/farmacologia , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/farmacologia
2.
J Minim Invasive Gynecol ; 28(9): 1568, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33894377

RESUMO

STUDY OBJECTIVE: To show a case of severe pelvic arteriovenous malformation (AVM) treated by laparoscopic internal iliac artery ligation after 2 uterine artery embolization (UAE) procedures, where successful pregnancy was achieved after surgery. DESIGN: Stepwise demonstration of the technique with a video. SETTING: Chinese PLA General Hospital. INTERVENTIONS: A 36-year-old woman with heavy menstrual bleeding was diagnosed with pelvic AVM by computed tomography scan. Before surgical intervention, she underwent 2 UAE procedures that temporarily reduced menstrual blood loss. Finally, we performed a laparoscopic internal iliac artery ligation on her. After the surgery, she conceived naturally. During the cesarean section, no AVMs were found. CONCLUSION: Laparoscopic internal iliac artery ligation can be a choice for patients who still have severe symptoms of AVM after UAE.


Assuntos
Malformações Arteriovenosas , Laparoscopia , Adulto , Malformações Arteriovenosas/complicações , Malformações Arteriovenosas/diagnóstico por imagem , Malformações Arteriovenosas/cirurgia , Cesárea , Feminino , Humanos , Artéria Ilíaca/diagnóstico por imagem , Artéria Ilíaca/cirurgia , Ligadura , Gravidez , Útero
3.
BMC Musculoskelet Disord ; 22(1): 628, 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34273965

RESUMO

OBJECTIVE: To preliminarily evaluate the safety and efficacy of the uncovertebral joint fusion cage in a goat model of cervical spine interbody fusion. METHODS: Twenty-four healthy adult goats were randomly assigned to one of the two following groups: Group A, goats were implanted with an uncovertebral joint fusion cage combined with a local autograft and Group B, goats were implanted with a non-profile cage filled with a local autograft. The goats were prospectively evaluated for 24 weeks and then were sacrificed for evaluation. X-rays, CT and micro-CT scanning, and undecalcified bone histological analysis were used for the evaluation of fusion. RESULTS: 75.0% (9/12) of the goats in Group A were evaluated as having fusion at 12 weeks, compared to 41.7% (5/12) in Group B. 83.3% (10/12) of the goats in Group A were evaluated as having fusion at 24 weeks compared to 58.3% (7/12) in Group B. The fusion grading scores in Group A were significantly higher than that in Group B both at 12 weeks and 24 weeks (P < 0.05). Micro-CT scanning and undecalcified bone histological analysis showed that new bone formation can be obviously found in the bilateral uncovertebral joint. The bone volume fraction (BV/ TV) in Group A (23.59 ± 4.43%) was significantly higher than Group B (16.16 ± 4.21%), with P < 0.05. CONCLUSIONS: Preliminary results of this study demonstrated that uncovertebral joint fusion cage is effective for achieving early bone formation and fusion without increase of serious complications.


Assuntos
Fusão Vertebral , Articulação Zigapofisária , Animais , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Discotomia , Cabras
4.
Angew Chem Int Ed Engl ; 59(48): 21488-21492, 2020 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-32777155

RESUMO

DNAzymes are widely used as functional units for creating DNA-based sensors and devices. Switching of DNAzyme activity by external stimuli is of increasing interest. Herein we report a CuII -responsive DNAzyme rationally designed by incorporating one of the most stabilizing artificial metallo-base pairs, a CuII -mediated carboxyimidazole base pair (ImC -CuII -ImC ), into a known RNA-cleaving DNAzyme. Cleavage of the substrate was suppressed without CuII , but the reaction proceeded efficiently in the presence of CuII ions. This is due to the induction of a catalytically active structure by ImC -CuII -ImC pairing. The on/off ratio was as high as 12-fold, which far exceeds that of the previously reported DNAzyme with a CuII -mediated hydroxypyridone base pair. The DNAzyme activity can be regulated specifically in response to CuII ions during the reaction through the addition, removal, or reduction of CuII . This approach should advance the development of stimuli-responsive DNA systems with a well-defined sharp switching function.


Assuntos
Complexos de Coordenação/metabolismo , Cobre/metabolismo , DNA Catalítico/metabolismo , Imidazóis/metabolismo , RNA/metabolismo , Pareamento de Bases , Complexos de Coordenação/química , Cobre/química , DNA Catalítico/química , Imidazóis/química , Estrutura Molecular , RNA/química
5.
Eur Spine J ; 28(10): 2359-2370, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31290025

RESUMO

PURPOSE: To investigate the influence of the immediate post-operative change in disc space angle relative to preoperation on heterotopic ossification (HO) occurrence following cervical disc arthroplasty (CDA) and on clinical and radiographic outcomes. METHODS: Eighty-four patients with single-level Prestige-LP arthroplasty were retrospectively reviewed. HO was assessed based on McAfee classification. Radiological parameters, including index disc space angle (DSA), functional spinal unit angle, cervical lordosis, segmental range of motion (SROM), migration and subsidence of the prosthesis, prosthesis-endplate coverage ratio, and complications, were evaluated. Clinical features and outcome scores were also evaluated. RESULTS: A significant association between immediate post-operative DSA change and HO occurrence was found. Patients with a more than 5° increase in immediate post-operative DSA lordosis had a significantly higher incidence of HO and more severe HO than patients with a less than 5° DSA increase after CDA. No correlation was observed between clinical outcomes and post-operative DSA increase or HO occurrence. Both groups maintained cervical sagittal alignment. However, patients with a more than 5° DSA increase exhibited larger anterior migration amount and lower prosthesis-endplate coverage ratio compared to a less than 5° increase in DSA, and more lordotic DSA and less SROM at the final follow-up compared with those at preoperation. No significant difference in other complications was found between the groups. CONCLUSION: Patients with a more than 5° increase in immediate post-operative DSA showed adverse effects on HO formation. Overcorrected DSA was associated with poor prosthesis stability, inadequate endplate coverage, and limited SROM, although it did not affect the clinical outcomes. These slides can be retrieved under Electronic Supplementary Material.


Assuntos
Artroplastia/efeitos adversos , Vértebras Cervicais , Disco Intervertebral , Ossificação Heterotópica , Complicações Pós-Operatórias , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/patologia , Vértebras Cervicais/fisiopatologia , Vértebras Cervicais/cirurgia , Humanos , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/patologia , Disco Intervertebral/fisiopatologia , Lordose , Amplitude de Movimento Articular , Estudos Retrospectivos , Resultado do Tratamento
6.
Chemistry ; 24(59): 15930-15936, 2018 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-30095192

RESUMO

Photocatalytic hydrogen evolution technology is recognized as a promising approach to relieving the growing energy crisis. Therefore, the development of a stable high-performance photocatalyst has long been the focus of research. In this work, quaternary composite materials involving a snowflake-like CdS nanocrystal wrapped by different amounts of polyoxometalate-decorated g-C3 N4 and polypyrrole (GPP@CdS) have been synthesized as photocatalysts for hydrogen production under visible-light irradiation. It has been revealed that the best composite (40 % GPP@CdS composite) exhibits hydrogen production activity of 1321 µmol, which exceeds that of CdS by a factor of more than two, and can be used in at least seven cycles with negligible loss of activity. The enhanced photocatalytic performance has been primarily attributed to the efficient synergy of CdS, g-C3 N4 , polypyrrole (PPy), and the polyoxometalate Ni4 (PW9 )2 . It should be noted that the introduction of PPy and g-C3 N4 into the title composite simultaneously promotes electron/hole pair separation and photocatalytic stability, whereas Ni4 (PW9 )2 serves as an efficient electron modulator and extra catalytic active site.

7.
Pharmazie ; 73(11): 666-670, 2018 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-30396387

RESUMO

Hovenia dulcis Thunb. is a traditional hepatoprotective Chinese medicine, and in research, much effort has been focused on the protection against alcoholic liver injury. In this study, the protective effects of a fruit ethanol extract of Hovenia dulcis (FE) against APAP-induced acute hepatotoxicity in mice and the possibly involved molecular mechanisms were investigated. Hepatoprotective activity of FE is clearly indicated by histopathological and biochemical examination. Treatment with FE resulted in inhibition of CYP2E1 activity involved in the transformation of APAP in vivo. Expressions of the altered bile acid metabolism and transport-related genes and relative proteins of apoptosis were normalized by preconditioning with FE before APAP treatment. These results suggested FE to alleviate APAP-induced liver injury in a dose-dependent manner by inhibition of cytochrome P450 activity, hepatocyte apoptosis and regulation of bile acid homeostasis imbalance.


Assuntos
Acetaminofen/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Extratos Vegetais/farmacologia , Rhamnaceae/química , Doença Aguda , Animais , Apoptose/efeitos dos fármacos , Ácidos e Sais Biliares/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Citocromo P-450 CYP2E1/efeitos dos fármacos , Citocromo P-450 CYP2E1/metabolismo , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Frutas , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Extratos Vegetais/administração & dosagem , Ratos Wistar
8.
Environ Sci Technol ; 51(6): 3518-3525, 2017 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-28230987

RESUMO

Exposure to antibiotics during pregnancy can pose a systematic effect on human health. A few biomonitoring studies have demonstrated an extensive exposure of children to antibiotics, but there is still a lack of data for pregnant women. To assess the exposure of pregnant women to antibiotics and potential health risk, we investigated 536 pregnant women aged 16-42 years from two geographically different study sites in Eastern China in 2015. We measured 21 antibiotics of five categories (seven fluoroquinolones, three phenicols, four tetracyclines, three macrolides, and four sulfonamides) in urine using the isotope dilution ultraperformance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. The hazard index (HI) was calculated on the basis of estimated daily exposure dose and acceptable daily intakes. A total of 16 antibiotics were found in urine, with detection frequencies between 0.2 and 16.0%. Antibiotics were overall detected in 41.6% of urine, and two or more antibiotics were detected in 13.1% of urine. Ciprofloxacin, ofloxacin, and trimethoprim were most frequently detected in urine, with detection frequencies between 10 and 20%. The majority of the antibiotics tested had an estimated daily exposure dose less than 1 µg/kg/day, and 4.3% of pregnant women had a HI value of more than 1. These findings indicated that pregnant women were frequently exposed to antibiotics and some individuals were in the potential risk of adverse microbiological effects induced by antibiotics.


Assuntos
Antibacterianos , Tetraciclinas , China , Feminino , Fluoroquinolonas , Humanos , Gravidez , Medição de Risco
9.
Cancer Sci ; 106(8): 1041-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-26079208

RESUMO

Hypoxia inducible factor-1α (HIF-1α) is associated with human breast cancer chemoresistance. Various reports have suggested that multiple pathways are involved in HIF-1α induction and that the molecular mechanisms regulating HIF-1α-induced chemoresistance are still not fully understood. Here, we report that anterior gradient 2 (AGR2), a proposed breast cancer biomarker, is an essential regulator in hypoxia-induced doxorubicin resistance through the binding and stabilization of HIF-1α. Our results show that knockdown of AGR2 in MCF-7 cells leads to the suppression of HIF-1α-induced doxorubicin resistance, whereas elevated levels of AGR2 in MDA-MB-231 cells enhance HIF-1α-induced doxorubicin resistance. AGR2 expression, in turn, is upregulated by the hypoxic induction of HIF-1α at both translational and transcriptional levels via a hypoxia-responsive region from -937 to -912 bp on the AGR2 promoter sequence. By specific binding to HIF-1α, the increased level of intracellular AGR2 stabilizes HIF-1α and delays its proteasomal degradation. Finally, we found that AGR2-stabilized HIF-1α escalates multiple drug resistance protein 1 (MDR1) mRNA levels and limits doxorubicin intake of MCF-7 cells, whereas MCF-7/ADR, a doxorubicin resistant cell line with deficient AGR2 and HIF-1α, acquires wild-type MDR1 overexpression. Our findings, for the first time, describe AGR2 as an important regulator in chemical hypoxia-induced doxorubicin resistance in breast cancer cells, providing a possible explanation for the variable levels of chemoresistance in breast cancers and further validating AGR2 as a potential anti-breast cancer therapeutic target.


Assuntos
Neoplasias da Mama/metabolismo , Resistencia a Medicamentos Antineoplásicos/fisiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Proteínas/metabolismo , Antineoplásicos/farmacologia , Western Blotting , Linhagem Celular Tumoral , Cobalto/farmacologia , Doxorrubicina/farmacologia , Feminino , Imunofluorescência , Humanos , Imunoprecipitação , Mucoproteínas , Proteínas Oncogênicas , RNA Interferente Pequeno , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transfecção
10.
Hum Mol Genet ; 22(5): 879-89, 2013 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-23184148

RESUMO

Mutations in ZIC3 cause human X-linked heterotaxy and isolated cardiovascular malformations. A mouse model with targeted deletion of Zic3 demonstrates an early role for Zic3 in gastrulation, CNS, cardiac and left-right axial development. The observation of multiple malformations in Zic3(null) mice and the relatively broad expression pattern of Zic3 suggest its important roles in multiple developmental processes. Here, we report that Zic3 is primarily required in epiblast derivatives to affect left-right patterning and its expression in epiblast is necessary for proper transcriptional control of embryonic cardiac development. However, cardiac malformations in Zic3 deficiency occur not because Zic3 is intrinsically required in the heart but rather because it functions early in the establishment of left-right body axis. In addition, we provide evidence supporting a role for Zic3 specifically in the perinodal region of the posterior lateral plate mesoderm for the establishment of laterality. These data delineate the spatial requirement of Zic3 during left-right patterning in the mammalian embryo, and provide basis for further understanding the molecular mechanisms underlying the complex interaction of Zic3 with signaling pathways involved in the early establishment of laterality.


Assuntos
Padronização Corporal/genética , Coração/crescimento & desenvolvimento , Proteínas de Homeodomínio/genética , Miocárdio/metabolismo , Fatores de Transcrição/genética , Animais , Embrião de Mamíferos , Regulação da Expressão Gênica no Desenvolvimento , Proteínas de Homeodomínio/metabolismo , Humanos , Mesoderma/embriologia , Mesoderma/metabolismo , Camundongos , Transdução de Sinais , Fatores de Transcrição/metabolismo
11.
Chirality ; 27(12): 936-43, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26425918

RESUMO

Rivaroxaban is an oral direct factor Xa (FXa) inhibitor clinically used to prevent and treat thromboembolic disorders. Drug-drug interaction (DDI) exist for rivaroxaban and the inhibitors of CYP3A4/5. This study aims to investigate the inhibition of rivaroxaban and its derivatives with a chiral center towards UDP-glucuronosyltransferases (UGTs). Chemical synthesis was performed to obtain rivaroxaban derivatives with different chiral centers. UGTs supersomes-catalyzed 4-methylumbelliferone (4-MU) glucuronidation was employed to evaluate the inhibition potential towards various UGT isoforms. A significant influence of rivaroxaban derivatives towards UGT1A3 was observed. Chiral centers produce different effects towards the effect of four pairs of rivaroxaban derivatives towards UGT1A3 activity, with stronger inhibition potential of S1 than R1, but stronger inhibition capability of R2, R3, R4 than S2, S3, and S4. Competitive inhibition of R3 and R4 towards UGT1A3 was demonstrated by Dixon and Lineweaver-Burk plots. In conclusion, the significant influence of rivaroxaban derivatives towards UGT1A3's activity was demonstrated in the present study. The chirality centers highly affected the inhibition behavior of rivaroxaban derivatives towards UGT1A3.


Assuntos
Inibidores do Fator Xa/farmacologia , Glucuronosiltransferase/antagonistas & inibidores , Isoenzimas/antagonistas & inibidores , Rivaroxabana/farmacologia , Inibidores do Fator Xa/química , Glucuronosiltransferase/química , Isoenzimas/química , Rivaroxabana/química , Estereoisomerismo
12.
BMC Cancer ; 14: 424, 2014 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-24923303

RESUMO

BACKGROUND: Ovarian cancer is the most lethal gynecologic malignancy, but its etiology remains poorly understood. This study investigated the role of Fli-1 in ovarian carcinogenesis and disease survival. METHODS: Fli-1 protein expression was evaluated by immunohistochemistry in 104 primary epithelial ovarian cancer (EOC) patients with known follow-up data and 20 controls. Correlation between Fli-1 expression and clinical characteristics was evaluated with the logistic regression. Kaplan Meier analysis was used to assess the impact of Fli-1 expression on overall survival (OS) and disease-free survival (DFS). Cell proliferation and migration assay were used to explore the function of Fli-1 in ovarian cancer cells. RESULTS: Fli-1 was expressed in 74% cases and up-regulated in EOC tissues compared with normal control tissues (p< 0.05). The high expression of Fli-1 was significantly associated with advanced tumor stage, positive lymph nodal involvement, and poor OS and DFS (p< 0.05). Further analysis showed Fli-1 is an independent prognostic factor for OS and DFS. Down-regulation of Fli-1 inhibited cell proliferation but did not affect cell migration in SKOV3 cells. CONCLUSIONS: This study revealed that Fli-1 played an essential role in the development and progression of ovarian cancers. Its overexpression is intimately related to malignant phenotypes and poor clinical outcome, suggesting that Fli-1 is a potential prognostic marker and therapeutic molecular target in ovarian cancer.


Assuntos
Biomarcadores Tumorais/metabolismo , Metástase Linfática/diagnóstico , Proteínas dos Microfilamentos/metabolismo , Neoplasias Ovarianas/diagnóstico , Receptores Citoplasmáticos e Nucleares/metabolismo , Estudos de Casos e Controles , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Metástase Linfática/patologia , Pessoa de Meia-Idade , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Prognóstico , Análise de Sobrevida , Transativadores
13.
Chem Commun (Camb) ; 60(3): 288-291, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38063055

RESUMO

A compact 8-17 DNAzyme was modified with a CuII-meditated artificial base pair to develop a metal-responsive allosteric DNAzyme. The base sequence was rationally designed based on the reported three-dimensional structure. The activity of the modified DNAzyme was enhanced 5.1-fold by the addition of one equivalent of CuII ions, showing good metal responsiveness. Since it has been challenging to modify compactly folded DNAzymes without losing their activity, this study demonstrates the utility of the metal-mediated artificial base pairing to create stimuli-responsive functional DNAs.


Assuntos
DNA Catalítico , DNA Catalítico/metabolismo , Pareamento de Bases , Metais/química , DNA/química , Sequência de Bases
14.
Chem Sci ; 15(7): 2365-2370, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-38362437

RESUMO

A CuII-responsive allosteric DNAzyme has been developed by introducing bifacial 5-carboxyuracil (caU) nucleobases, which form both hydrogen-bonded caU-A and metal-mediated caU-CuII-caU base pairs. The base sequence was logically designed based on a known RNA-cleaving DNAzyme so that the caU-modified DNAzyme (caU-DNAzyme) can form a catalytically inactive structure containing three caU-A base pairs and an active form with three caU-CuII-caU pairs. The caU-DNAzyme was synthesized by joining short caU-containing fragments with a standard DNA ligase. The activity of caU-DNAzyme was suppressed without CuII, but enhanced 21-fold with the addition of CuII. Furthermore, the DNAzyme activity was turned on and off during the reaction by the addition and removal of CuII ions. Both ligase-mediated synthesis and CuII-dependent allosteric regulation were achieved by the bifacial base pairing properties of caU. This study provides a new strategy for designing stimuli-responsive DNA molecular systems.

15.
Chem Commun (Camb) ; 59(7): 892-895, 2023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36594822

RESUMO

Artificial metal-mediated DNA base pairing is a promising strategy for creating highly functionalized DNA supramolecules. Here we report a novel ligand-type triazole-4-carboxylate (TazC) nucleoside that is readily prepared by the click reaction. TazC nucleosides were found to form a stable TazC-CuII-TazC base pair inside DNA duplexes, resulting in CuII-specific duplex stabilization (ΔTm = +7.7 °C). This study demonstrates that the triazole derivatives are useful in the development of metal-mediated base pairing.


Assuntos
Química Click , Nucleosídeos , Nucleosídeos/química , Pareamento de Bases , DNA/química , Metais/química , Ácidos Carboxílicos
16.
Medicine (Baltimore) ; 102(20): e33692, 2023 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-37335718

RESUMO

RATIONALE: Uterine artery spontaneous rupture is a rare but potentially life-threatening complication during pregnancy and puerperium. The lack of typical symptoms makes it difficult to diagnose, which can result in serious consequences for both the mother and fetus. PATIENT CONCERNS: Case 1 presented with fainting and lower abdominal discomfort, while Case 2 developed hypotension after delivery and remained in poor condition even after rehydration. DIAGNOSES: Both cases were diagnosed with uterine artery spontaneous rupture, with intraoperative findings revealing ruptures in different branches of the uterine artery. INTERVENTIONS: Both cases underwent surgical interventions, with laparoscopic surgery performed in Case 1 and repair of the ruptured artery in Case 2. OUTCOMES: Both cases had successful outcomes, with the ruptured arteries repaired and the patients discharged from the hospital within a week after surgery. LESSONS: Uterine artery spontaneous rupture is a rare but potentially life-threatening complication that may present with atypical symptoms. Early diagnosis and prompt surgical intervention are crucial in preventing serious complications for both the mother and fetus. Clinicians should maintain a high level of suspicion for this condition when evaluating patients presenting with unexplained symptoms or signs of peritoneal irritation during pregnancy and puerperium.


Assuntos
Artéria Uterina , Ruptura Uterina , Gravidez , Feminino , Humanos , Artéria Uterina/cirurgia , Ruptura Uterina/etiologia , Ruptura Espontânea/cirurgia , Ruptura Espontânea/complicações , Pelve , Período Pós-Parto
17.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 39(7): 610-616, 2023 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-37403720

RESUMO

Objective To investigate the effects of formononetin (FMN) on cognitive behavior and inflammation in aging rats with chronic unpredictable mild stress (CUMS). Methods SD rats aged about 70 weeks were divided into healthy control group, CUMS model group, CUMS combined with 10 mg/kg FMN group, CUMS combined with 20 mg/kg FMN group and CUMS combined with 1.8 mg/kg fluoxetine hydrochloride (Flu) group. Except for healthy control group, other groups were stimulated with CUMS and administered drugs for 28 days. Sugar water preference, forced swimming experiment and open field experiment were used to observe the emotional behavior of rats in each group. HE staining was used to observe the pathological injury degree of brain equine area. The contents of 5-hydroxytryptamine (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) were detected by the kit. The apoptosis was tested by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) in the brain tissue. The levels of tumor necrosis factor α (TNF-α), inducible nitric oxide synthase (iNOS) and interleukin 6 (IL-6) in peripheral blood were measured by ELISA. Western blot analysis was used to detect Bcl2, Bcl2 associated X protein (BAX), cleaved caspase-9, cleaved caspase-3, Toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and phosphorylated nuclear factor κB p65 (p-NF-κB p65) in brain tissues. Results Compared with CUMS model group, sugar water consumption, open field activity time, open field travel distance and swimming activity time significantly increased in the CUMS combined with 20 mg/kg FMN group and the CUMS combined with 1.8 mg/kg Flu group. The number of new outarm entry increased significantly, while the number of initial arm entry and other arm entry decreased significantly. The pathological damage of brain equine area was alleviated, and the contents of 5-HT and 5-HIAA were significantly increased. The ratio of BAX/Bcl2 and the expression of cleaved caspase-9 and cleaved caspase-3 protein as well as the number of apoptotic cells were significantly decreased. The contents of TNF-α, iNOS and IL-6 were significantly decreased. The protein levels of TLR4, MyD88 and p-NF-κB p65 were significantly decreased. Conclusion FMN can inhibit the release of inflammatory factors by blocking NF-κB pathway and improve cognitive and behavioral ability of CUMS aged rats.


Assuntos
Comportamento Animal , Hipocampo , Isoflavonas , NF-kappa B , Transdução de Sinais , Estresse Fisiológico , Animais , Ratos , Cognição/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Hipocampo/fisiopatologia , NF-kappa B/antagonistas & inibidores , NF-kappa B/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Isoflavonas/farmacologia , Envelhecimento , Comportamento Animal/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Anti-Inflamatórios/farmacologia
18.
Cell Metab ; 5(2): 129-42, 2007 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-17276355

RESUMO

The Cdk7/cyclin H/ménage-à-trois 1 (MAT1) heterotrimer has proposed functions in transcription as the kinase component of basal transcription factor TFIIH and is activated in adult hearts by Gq-, calcineurin-, and biomechanical stress-dependent pathways for hypertrophic growth. Using cardiac-specific Cre, we have ablated MAT1 in myocardium. Despite reduced Cdk7 activity, MAT1-deficient hearts grew normally, but fatal heart failure ensued at 6-8 weeks. By microarray profiling, quantitative RT-PCR, and western blotting at 4 weeks, genes for energy metabolism were found to be suppressed selectively, including targets of peroxisome proliferator-activated receptor gamma coactivator 1 (PGC-1). Cardiac metabolic defects were substantiated in isolated perfused hearts and isolated mitochondria. In culture, deleting MAT1 with Cre disrupted PGC-1 function: PGC-1alpha failed to activate PGC-1-responsive promoters and nuclear receptors, GAL4-PGC-1alpha was functionally defective, and PGC-1beta was likewise deficient. PGC-1 bound to both MAT1 and Cdk7 in coprecipitation assays. Thus, we demonstrate a requirement for MAT1 in the operation of PGC-1 coactivators that control cell metabolism.


Assuntos
Sistemas de Transporte de Aminoácidos Neutros/metabolismo , Fatores de Transcrição/genética , Transcrição Gênica , Animais , Apoptose , Cardiomiopatias/genética , Cardiomiopatias/patologia , Proteínas de Ciclo Celular , Sobrevivência Celular , Quinases Ciclina-Dependentes/metabolismo , Receptor com Domínio Discoidina 1 , Deleção de Genes , Regulação da Expressão Gênica , Proteína Vmw65 do Vírus do Herpes Simples/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Miocárdio/enzimologia , Miocárdio/patologia , Fosforilação , Ligação Proteica , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Proteína Tirosina Quinases/metabolismo , Receptores de Estrogênio/metabolismo , Fatores de Transcrição/metabolismo , Receptor ERRalfa Relacionado ao Estrogênio
19.
Arch Gynecol Obstet ; 286(2): 389-93, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22441658

RESUMO

OBJECTIVE: To determine the effects of carbon dioxide (CO(2)) and nitrogen (N(2)) pneumoperitoneums on endometriosis (EMs) lesions. METHODS: Female Wistar rats were randomized into the following 3 groups: CO(2) (N = 20), N(2) (N = 22) and air pneumoperitoneums (N = 9). After 5 weeks of establishment models, do the pneumoperitoneums. Then measure the size of EMs lesions and the related factors of serum and tissue after 1, 2, and 4 weeks of pneumoperitoneums. RESULTS: (1) One week after the pneumoperitoneum was established, the EMs lesions in the CO(2) group were largest in volume, whereas at 4 weeks the EMs lesions in the CO(2) group were smaller than the N(2) group. (2) The level of ICAM-1 and TIMP-2 of serum in CO(2) and N(2) group after 2 weeks of pneumoperitoneum were higher than air group. (3) The expression of CD44v6, ICAM-1, MMP-2 and VEGF of tissue in CO(2) and N(2) group after 1, 2 and 4 weeks of pneumoperitoneum were lower than air group, TIMP-2 and ENS were higher than air group. CONCLUSION: After a CO(2) pneumoperitoneum, EMs lesions were reduced in volume, suggesting an inhibitory effect on EMs lesions.


Assuntos
Dióxido de Carbono/uso terapêutico , Endometriose/terapia , Nitrogênio/uso terapêutico , Pneumoperitônio Artificial/métodos , Animais , Endostatinas/biossíntese , Feminino , Receptores de Hialuronatos/biossíntese , Molécula 1 de Adesão Intercelular/sangue , Metaloproteinase 2 da Matriz/biossíntese , Ratos , Ratos Wistar , Inibidor Tecidual de Metaloproteinase-2/sangue , Fator A de Crescimento do Endotélio Vascular/biossíntese
20.
Chem Sci ; 13(14): 3977-3983, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35440985

RESUMO

Metal-mediated DNA base pairs, which consist of two ligand-type artificial nucleobases and a bridging metal ion, have attracted increasing attention in recent years as a different base pairing mode from natural base pairing. Metal-mediated base pairing has been extensively studied, not only for metal-dependent thermal stabilisation of duplexes, but also for metal assembly by DNA templates and construction of functional DNAs that can be controlled by metals. Here, we report the metal-mediated base paring properties of a novel 2-oxo-imidazole-4-carboxylate (ImOC) nucleobase and a previously reported 2-oxo-imidazole-4-carboxamide (ImOA) nucleobase, both of which can be easily derived from a commercially available uridine analogue. The ImOC nucleobases were found to form stable ImOC-CuII-ImOC and ImOC-HgII-ImOC base pairs in the presence of the corresponding metal ions, leading to an increase in the duplex melting temperature by +20 °C and +11 °C, respectively. The ImOC bases did not react with other divalent metal ions and showed superior metal selectivity compared to similar nucleobase design reported so far. The ImOC-CuII-ImOC base pair was much more stable than mismatch pairs with other natural nucleobases, confirming the base pair specificity in the presence of CuII. Furthermore, we demonstrated the quantitative assembly of three CuII ions inside a DNA duplex with three consecutive ImOC-ImOC pairs, showing great potential of DNA-template based CuII nanoarray construction. The study of easily-prepared ImOC base pairs will provide a new design strategy for metal-responsive DNA materials.

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