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1.
Pediatr Res ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438553

RESUMO

BACKGROUND: To facilitate the identification of less common clinical phenotypes of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) in children. METHODS: We retrospectively reviewed medical records of 236 patients with MOGAD. The following phenotypes were considered to be typical for MOGAD: ADEM, ON, TM, and NMOSD. Less common onset clinical phenotypes were screened out; their clinical and magnetic resonance imaging (MRI), diagnosis, treatment, and prognosis were summarized and analyzed. RESULTS: 16 cases (6.8%) presented as cortical encephalitis, with convulsions, headache, and fever as the main symptoms. 15 cases were misdiagnosed in the early period. 13 cases (5.5%) showed the overlapping syndrome of MOGAD and anti-N-methyl-D aspartate receptor encephalitis (MNOS), with seizures (92.3%) being the most common clinical symptom. 11 cases (84.6%) showed relapses. The cerebral leukodystrophy-like phenotype was present in seven cases (3.0%), with a recurrence rate of 50%. Isolated seizures without any findings on MRI phenotype was present in three cases (1.3%), with the only clinical symptom being seizures of focal origin. Three cases (1.3%) of aseptic meningitis phenotype presented with prolonged fever. CONCLUSION: 40/236 (16.9%) of children with MOGAD had less common phenotypes. Less common clinical phenotypes of pediatric MOGAD are susceptible to misdiagnosis and deserve more attention. IMPACT: This is the first comprehensive analysis and summary of all less commonl clinical phenotypes of MOGAD in children, while previous studies have only focused on a specific phenotype or case reports. We analyzed the characteristics of MOGAD in children and further revealed the reasons why these less common clinical phenotypes are prone to misdiagnosis and deserve more attention. Our research on treatment has shown that early detection of MOG antibodies and early treatment are of great significance for improving the prognosis of these patients.

2.
J Cardiovasc Pharmacol ; 84(1): 18-25, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38968565

RESUMO

ABSTRACT: Recent studies have revealed the benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in heart failure patients. However, their effects on acute myocardial infarction (AMI) remain uncertain. Therefore, we conducted this meta-analysis to assess the effectiveness of SGLT2i in patients with AMI with or without diabetes. We conducted a comprehensive search of PubMed, Embase, and Cochrane Library encompassing data from inception until November 30, 2023. Relevant studies comparing SGLT2i with placebo or non-SGLT2i in patients with AMI were included. The mean difference and/or odds ratio (OR) with 95% confidence intervals were pooled using a fixed-effects model when the heterogeneity statistic (I2) was less than 50%; otherwise, a random-effects model was employed. Four randomized controlled trials and 4 observational studies involving 9397 patients with AMI were included in this meta-analysis. Patients treated with SGLT2i exhibited a significantly lower rate of hospitalization for heart failure (OR = 0.50, 95% CI: 0.32-0.80) and all-cause death (OR = 0.65, 95% CI: 0.44-0.95) compared with those treated with placebo or non-SGLT2i. Furthermore, the use of SGLT2i was associated with a significant increase in left ventricular ejection fraction (mean difference = 1.90, 95% CI: 1.62-2.17) and a greater reduction of N-terminal prohormone of brain natriuretic peptide (OR = 0.88, 95% CI 0.82-0.94). Subgroup analysis revealed that in patients with diabetes, SGLT2i exhibited similar effects. The present meta-analysis provided evidence indicating the effectiveness of SGLT2i in patients with AMI; SGLT2i may serve as an additional therapeutic option for patients with AMI, regardless of the presence or absence of diabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Insuficiência Cardíaca , Infarto do Miocárdio , Ensaios Clínicos Controlados Aleatórios como Assunto , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Resultado do Tratamento , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/diagnóstico , Masculino , Pessoa de Meia-Idade , Feminino , Idoso , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/fisiopatologia , Insuficiência Cardíaca/diagnóstico , Estudos Observacionais como Assunto , Fatores de Risco , Medição de Risco , Recuperação de Função Fisiológica , Fatores de Tempo
3.
Lipids Health Dis ; 23(1): 122, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38678208

RESUMO

BACKGROUND: Previous studies have demonstrated that trans fatty acids (TFAs) intake was linked to an increased risk of chronic diseases. As a novel systemic inflammatory biomarker, the clinical value and efficacy of the systemic immune-inflammation index (SII) have been widely explored. However, the association between TFAs and SII is still unclear. Therefore, the study aims to investigate the connection between TFAs and SII in US adults. METHODS: The study retrieved data from the National Health and Nutrition Examination Survey (NHANES) for the years 1999-2000 and 2009-2010. Following the exclusion of ineligible participants, the study encompassed a total of 3047 individuals. The research employed a multivariate linear regression model to investigate the connection between circulating TFAs and SII. Furthermore, the restricted cubic spline (RCS) model was utilized to evaluate the potential nonlinear association. Subgroup analysis was also conducted to investigate the latent interactive factors. RESULTS: In this investigation, participants exhibited a mean age of 47.40 years, with 53.91% of them being female. Utilizing a multivariate linear regression model, the independent positive associations between the log2-transformed palmitelaidic acid, the log2 transformed-vaccenic acid, the log2-transformed elaidic acid, the log2-transformed linolelaidic acid, and the log2-transformed-total sum of TFAs with the SII (all P < 0.05) were noted. In the RCS analysis, no nonlinear relationship was observed between the log2-transformed palmitelaidic acid, the log2 transformed-vaccenic acid, the log2-transformed elaidic acid, the log2-transformed linolelaidic acid, the log2-transformed-total sum of TFAs and the SII (all P for nonlinear > 0.05). For the stratified analysis, the relationship between the circulating TFAs and the SII differed by the obesity status and the smoking status. CONCLUSIONS: A positive association was investigated between three types of TFA, the sum of TFAs, and the SII in the US population. Additional rigorously designed studies are needed to verify the results and explore the potential mechanism.


Assuntos
Inflamação , Ácidos Graxos trans , Humanos , Ácidos Graxos trans/sangue , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Transversais , Adulto , Inflamação/sangue , Inflamação/imunologia , Inquéritos Nutricionais , Ácidos Oleicos , Modelos Lineares , Biomarcadores/sangue
4.
Cancer Immunol Immunother ; 72(12): 3895-3917, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37796300

RESUMO

Macrophages are important precursor cell types of the innate immune system and bridge adaptive immune responses through the antigen presentation system. Meanwhile, macrophages constitute substantial portion of the stromal cells in the tumor microenvironment (TME) (referred to as tumor-associated macrophages, or TAMs) and exhibit conflicting roles in the development, invasion, and metastasis of thyroid cancer (TC). Moreover, TAMs play a crucial role to the behavior of TC due to their high degree of infiltration and prognostic relevance. Generally, TAMs can be divided into two subgroups; M1-like TAMs are capable of directly kill tumor cells, and recruiting and activating other immune cells in the early stages of cancer. However, due to changes in the TME, M2-like TAMs gradually increase and promote tumor progression. This review aims to discuss the impact of TAMs on TC, including their role in tumor promotion, gene mutation, and other factors related to the polarization of TAMs. Finally, we will explore the M2-like TAM-centered therapeutic strategies, including chemotherapy, clinical trials, and combinatorial immunotherapy.


Assuntos
Neoplasias da Glândula Tireoide , Macrófagos Associados a Tumor , Humanos , Neoplasias da Glândula Tireoide/terapia , Prognóstico , Macrófagos , Imunoterapia , Microambiente Tumoral
5.
Int J Mol Sci ; 24(6)2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36982954

RESUMO

The gut microbiota is increasingly considered to play a key role in human immunity and health. The aging process alters the microbiota composition, which is associated with inflammation, reactive oxygen species (ROS), decreased tissue function, and increased susceptibility to age-related diseases. It has been demonstrated that plant polysaccharides have beneficial effects on the gut microbiota, particularly in reducing pathogenic bacteria abundance and increasing beneficial bacteria populations. However, there is limited evidence of the effect of plant polysaccharides on age-related gut microbiota dysbiosis and ROS accumulation during the aging process. To explore the effect of Eucommiae polysaccharides (EPs) on age-related gut microbiota dysbiosis and ROS accumulation during the aging process of Drosophila, a series of behavioral and life span assays of Drosophila with the same genetic background in standard medium and a medium supplemented with EPs were performed. Next, the gut microbiota composition and protein composition of Drosophila in standard medium and the medium supplemented with EPs were detected using 16S rRNA gene sequencing analysis and quantitative proteomic analysis. Here, we show that supplementation of Eucommiae polysaccharides (EPs) during development leads to the life span extension of Drosophila. Furthermore, EPs decreased age-related ROS accumulation and suppressed Gluconobacter, Providencia, and Enterobacteriaceae in aged Drosophila. Increased Gluconobacter, Providencia, and Enterobacteriaceae in the indigenous microbiota might induce age-related gut dysfunction in Drosophila and shortens their life span. Our study demonstrates that EPs can be used as prebiotic agents to prevent aging-associated gut dysbiosis and reactive oxidative stress.


Assuntos
Drosophila , Disbiose , Humanos , Animais , Idoso , Drosophila/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Disbiose/tratamento farmacológico , RNA Ribossômico 16S/genética , Proteômica , Polissacarídeos/farmacologia , Envelhecimento , Enterobacteriaceae , Expectativa de Vida
6.
Neurochem Res ; 47(2): 481-492, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34623561

RESUMO

Vincristine is a common chemotherapeutic agent in cancer treatment, while it often causes chemotherapy-induced peripheral neuropathy(CIPN), which brings patients a great disease burden and associated economic pressure. The mechanism under CIPN remains mostly unknown. The previous study has shown that cell-type-specific spinal synaptic plasticity in the dorsal horn plays a pivotal role in neuropathic pain. Downregulation of GABA transmission, which mainly acts as an inhibitory pathway, has been reported in the growing number of research. Our present study found that GAD67, responsible for > 90% of basal GABA synthesis, is down-regulated, while its relative mRNA remains unchanged in vincristine-induced neuropathy. Considering microRNAs (miRNAs) as a post-transcription modifier by degrading targeted mRNA or repressing mRNA translation, we performed genome-wide miRNA screening and revealed that miR-30d might contribute to GAD67 down-regulation. Further investigation confirmed that miR-30d could affect the fluorescence activity of GAD67 by binding to the 3 'UTR of the GAD67 gene, and intrathecal injection of miR-30d antagomir increased the expression of GAD67, partially rescued vincristine-induced thermal hyperalgesia and mechanical allodynia. In summary, our study revealed the molecule interactions of GAD67 and miR-30d in CIPN, which has not previously been discussed in the literature. The results give more profound insight into understanding the CIPN mechanism and hopefully helps pain control.


Assuntos
MicroRNAs , Neuralgia , Animais , Humanos , Hiperalgesia/induzido quimicamente , Hiperalgesia/metabolismo , Neuralgia/metabolismo , Ratos , Ratos Sprague-Dawley , Vincristina/toxicidade
7.
Inorg Chem ; 61(49): 20159-20168, 2022 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-36450105

RESUMO

Two coordination polymers (CPs), namely, [Mn3(L)2(4,4'-bipy)2(H2O)2]n (1) and [Ni(L1)(1,4-bib)(H2O)]n (2) (H3L = 5-(3-bromo-4-carboxyphenoxy)isophthalic acid, H2L1 = 5-(3-hydroxyphenoxy)isophthalic acid, 4,4'-bpy = 4,4'-bipyridine, and 1,4-bib = 1,4-bis(1H-imidazol-1-yl)benzene), were synthesized under hydrothermal conditions. Most notably, with the help of the bromine atom-inducing effect, ligand transformation was observed in the structure of complex 2, which was scrutinized thoroughly by single crystal X-ray crystallography and X-ray photoelectron spectroscopy (XPS). Strikingly, Ni(II) ions were utilized as both coordinated atoms and as a catalyst for in situ Br-OH exchange of H3L in the process, as a result of which the product would have preferred to form a one-dimensional chain. The same reaction cannot happen in 1, leading to form a two-dimensional structure. Moreover, Ni(II)-catalyzed and magnetic exchange mechanisms were well interpreted using density functional theory (DFT) calculations. Finally, complexes 1-2 show three-dimensional (3D) supramolecular structures because of intermolecular weak interactions (C-Br···π, C-H···π, C-H···O, and π···π stacking) and exhibit utterly different antiferrimagnetic coupling interactions.


Assuntos
Ácidos Ftálicos , Modelos Moleculares , Teoria da Densidade Funcional , Fenômenos Magnéticos
8.
Anal Bioanal Chem ; 414(7): 2493-2503, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35171297

RESUMO

Sol-gel materials have been widely used for solid-phase microextraction (SPME) coatings due to their outstanding performance; in contrast, sol-gel SPME coatings have seldom been used for in vivo sampling. The main reason is that their matrix compatibility is unclear. In order to promote the application of this type of coating and accelerate the development of in vivo SPME, in this study, the matrix compatibility of several typical sol-gel coatings was assessed in plasma and whole blood using phthalic acid esters as analytes. The service life of five kinds of sol-gel coatings was among 20-35 times in undiluted plasma, while it was 27 times for a homemade commercial polydimethylsiloxane coating, which indicates good matrix compatibility of sol-gel coatings in untreated plasma. The sol-gel hydroxy-terminated silicone oil/methacrylic acid fiber achieved the highest extraction ability among all of the fibers, and it was tested in pig whole blood. It could be continuously used for at least 22 times, demonstrating good potential for in vivo sampling. Subsequently, a direct-immersion SPME/gas chromatography-flame ionization detection method was established for the determination of 5 phthalic acid esters in blood. Compared with other methods reported in the literature, this method is rapid, simple, sensitive, and accurate, and does not need expensive instruments or tedious procedures. A simulation system of animal blood circulation was constructed to verify the practicability of sol-gel SPME coatings in animal vein sampling. The result illustrated the feasibility of that coating for in vivo blood sampling, but a more accurate quantification calibration approach needs to be explored.


Assuntos
Ácidos Ftálicos , Microextração em Fase Sólida , Animais , Cromatografia Gasosa/métodos , Ésteres , Microextração em Fase Sólida/métodos , Suínos
9.
Neurochem Res ; 46(5): 1214-1223, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33550530

RESUMO

Paclitaxel is a common chemotherapeutic agent in cancer treatment, while it often causes chemotherapy-induced peripheral neuropathy (CIPN), which manifested as hyperalgesia and allodynia, and its mechanism remains largely unknown. The previous study has shown that matrix metalloproteinase-2 (MMP-2) plays a pivotal role in spinal nerve ligation (SNL) induced neuropathic pain, but its function in CIPN and exact molecular mechanisms underlying upregulation is not explored. Our present study revealed that MMP-2 is also upregulated in paclitaxel induced neuropathic pain (NP), and knockdown it by siRNA can ameliorate mechanical allodynia. Since DNA methylation is closely related to gene transcription, we explored the methylation status of the MMP-2 gene and demonstrated that MMP-2 upregulation is related to the reduced methylation level of its promoter. DNA methylation is mediated by DNA methyltransferases (DNMTs), and previous studies suggested that three main types of DNMTs can undergo SUMOylation. Our next study revealed that SUMO1 modification of DNMT3b is significantly enhanced. Intrathecal administration of SUMOylation inhibitor, ginkgolic acid (GA), could reverse enhanced SUMO1 modification of DNMT3b and upregulation of MMP-2 in the model rats. Further investigation suggested that DNMT3b binding activity to the promoter region of the MMP-2 gene is significantly decreased in paclitaxel treated rats, and the administration of GA can reverse these effects, which is also accompanied by changes in the promoter methylation status of the MMP-2 gene. Our study demonstrates that MMP-2 up-regulation mediated by DNMT3b SUMOylation is essential for paclitaxel induced NP development, which brings us new therapeutic options for CIPN.


Assuntos
DNA (Citosina-5-)-Metiltransferases/metabolismo , Hiperalgesia/metabolismo , Metaloproteinase 2 da Matriz/metabolismo , Paclitaxel/farmacologia , Sumoilação/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Animais , DNA/metabolismo , Metilação de DNA/efeitos dos fármacos , Técnicas de Silenciamento de Genes , Hiperalgesia/induzido quimicamente , Masculino , Metaloproteinase 2 da Matriz/genética , Neuralgia/induzido quimicamente , Regiões Promotoras Genéticas/fisiologia , RNA Interferente Pequeno/farmacologia , Ratos Sprague-Dawley , Corno Dorsal da Medula Espinal/metabolismo , DNA Metiltransferase 3B
10.
Int J Neurosci ; 130(4): 336-342, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31665950

RESUMO

Background: Treatment of neonatal seizures includes etiotropic and anticonvulsant treatments. However, anticonvulsant use in neonates is off-label and requires ethical review.Objective: To investigate the efficacy and safety of levetiracetam for neonatal seizures and to establish a predictive model.Methods: We retrospectively analyzed 125 neonatal seizure cases (phenobarbital 66 cases, levetiracetam 59 cases). The efficacy, safety and tolerability of levetiracetam were evaluated by cox regression survival analysis and a regression tree prediction model for the 16-week time point.Results: There was no significant difference between phenobarbital and levetiracetam treatment group in short-term efficacy (p > 0.05). But the cumulative survival function suggested that levetiracetam treatment group was better than phenobarbital (p = 0.026) in long-term efficacy evaluation. Neurodevelopmental assessments at 16 weeks showed that levetiracetam had better effect on the neurodevelopmental level (Gesell scores in response) than phenobarbital (p = 0.011). The main adverse events with levetiracetam were irritability and anorexia. According to the regression tree prediction model, the top three factors influencing the therapeutic effect were pre-treatment seizure frequency, age of onset and etiological classification.Conclusion: Levetiracetam shows good efficacy, safety and tolerability for the long-term neonatal seizure treatment.


Assuntos
Anticonvulsivantes/uso terapêutico , Levetiracetam/uso terapêutico , Convulsões/tratamento farmacológico , Feminino , Humanos , Recém-Nascido , Masculino , Uso Off-Label , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Resultado do Tratamento
11.
Molecules ; 24(24)2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31817260

RESUMO

An in situ tracing study based on solid-phase microextraction (SPME) was conducted to investigate the uptake and elimination of organophosphorus pesticides in apples. A matrix-compatible polydimethylsiloxane/poly(styrene-co-divinylbenzene)/polydimethylsiloxane fiber was produced to meet the needs of in situ sampling. The fiber had high extraction ability, good sensitivity and accuracy with respect to the analytes in apple pulp, and could be used 85 times. Although the sampling rate was changing over time, quantification was still achieved by the sampling rate calibration method. Some factors that affect its applicability were studied. The limits of detection were 0.18 ng/g for diazinon and 0.20 ng/g for chlorpyrifos, rather lower than the maximum residue limits of the National Food Safety Standard of China (GB 2763-2016) and the European Commission (Reg.(EU) No 834/2013, 2018/686). The accuracy of in situ SPME quantification was verified by comparing with the results obtained by the traditional liquid-liquid extraction method. In this work, the in situ sampling method is developed using apples, diazinon, and chlorpyrifos as a model system; however, this method can be used for in vivo analysis of fruits and vegetables for nutrition and safety monitoring.


Assuntos
Malus/química , Compostos Organofosforados/análise , Praguicidas/análise , Microextração em Fase Sólida/métodos , Calibragem , Clorpirifos/análise , Cromatografia Gasosa , Diazinon/análise , Temperatura
12.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(3): 223-228, 2019 Mar.
Artigo em Zh | MEDLINE | ID: mdl-30907344

RESUMO

OBJECTIVE: To study the clinical features of children with acute disseminated encephalomyelitis (ADEM) and related recurrence factors. METHODS: A retrospective analysis was performed for the clinical data and prognosis of 73 children with ADEM who were hospitalized from November 2011 to January 2017. RESULTS: Among the 73 children, 41 (56%) had a history of infection before onset and 7 (10%) had a history of vaccination. All children had the symptoms of encephalopathy, including disturbance of consciousness in 47 children (64%) and mental and behavioral disorders in 54 children (74%). Pyrexia was observed in 53 children (73%), dyskinesia in 47 children (64%), headache in 47 children (64%) and vomiting in 40 children (55%). Brain MRI was performed for 65 children and the results showed involvement of the subcortical white matter (83%, 54/65), the deep nuclei (60%, 39/65), the brain stem (58%, 38/65) and the cerebellum (42%, 27/65). Spinal cord involvement was observed in 20 children (20/43, 47%). A total of 15 children experienced recurrence during follow-up. Compared with the non-recurrence group, the recurrence group had significantly higher percentages of children with deep nucleus involvement (P<0.05), with injury in ≥3 spinal segments (P<0.01) and with a time from disease onset to gamma-globulin/hormone treatment of >2 weeks (P<0.05). CONCLUSIONS: ADEM in children have various clinical manifestations. A small number of children may experience recurrence. Deep nucleus involvement on MRI, long spinal segmental injury (≥3 segments) and late treatment with gamma-globulin/hormone (>2 weeks) may be associated with the recurrence of ADEM.


Assuntos
Encefalomielite Aguda Disseminada , Criança , Humanos , Imageamento por Ressonância Magnética , Prognóstico , Recidiva , Estudos Retrospectivos
13.
J Therm Biol ; 71: 189-194, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29301689

RESUMO

The initiation of torpor is supposed to be related to the availability of metabolic fuels. Studies on metabolic fuel inhibition of glucose by using 2-deoxy-D-glucose (2DG) or fatty acid by mercaptoacetate (MA) in heterothermic mammals produced mixed outcomes. To examine the roles of availability of glucose and fatty acid in the initiation of torpor in desert hamsters (Phodopus roborovskii), we intraperitoneally administrated 2DG and MA to summer-acclimated male hamsters while body temperature (Tb), metabolic rate (MR) and respiratory quotient (RQ) were simultaneously recorded to monitor their thermoregulatory response. 2DG induced a reversible reduction of Tb in desert hamsters both at ambient temperature (Ta) of 23°C and 5°C. At Ta of 23°C, Tb, MR and RQ decreased in a dose-dependent manner with a large Tb-Ta differential (> 6.5°C) and a lowest Tb of 28.0°C which were comparable to those in fasted hamsters. At Ta of 5°C, 2DG-treated hamsters also decreased Tb to the same level as at Ta 23°C, but MR was significantly higher than that at Ta of 23°C at each dose, suggesting doses of 2DG directly affected the hypothalamic Tb set-point. Different from fasted hamsters which maintain normothermic at Ta of 5°C, 2DG-treated hamsters showed a substantial reduction of Tb at Ta 5°C, indicating an overwhelming effect on the thermoregulatory system regardless of Ta. Furthermore, the rapid decrease of Tb and outstretched body posture in 2DG-treated hamsters suggest that the effects of 2DG were not simply mimicking the torpor pathways but that other mechanisms are involved. Interestingly, MA failed to induce a torpor-like state in male desert hamsters. Our results suggest that availability of glucose rather than fatty acid plays an important role for initiation of torpor in desert hamsters.


Assuntos
Antimetabólitos/farmacologia , Temperatura Corporal/efeitos dos fármacos , Desoxiglucose/farmacologia , Phodopus/fisiologia , Tioglicolatos/farmacologia , Animais , Metabolismo Basal , Cricetinae , Hipotálamo/fisiologia , Masculino , Respiração , Torpor/efeitos dos fármacos
14.
Cell Physiol Biochem ; 44(5): 1741-1748, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29216623

RESUMO

BACKGROUND/AIMS: Treatment of breast cancer remains a clinical challenge. This study aims to validate exosomal microRNA-1246 (miR-1246) as a serum biomarker for breast cancer and understand the underlying mechanism in breast cancer progression. METHODS: The expression levels of endogenous and exosomal miRNAs were examined by real time PCR, and the expression level of the target protein was detected by western blot. Scanning electron and confocal microscopy were used to characterize exosomes and to study their uptake and transfer. Luciferase reporter plasmids and its mutant were used to confirm direct targeting. Furthermore, the functional significance of exosomal miR-1246 was estimated by invasion assay and cell viability assay. RESULTS: In this study, we demonstrate that exosomes carrying microRNA can be transferred among different cell lines through direct uptake. miR-1246 is highly expressed in metastatic breast cancer MDA-MB-231 cells compared to non-metastatic breast cancer cells or non-malignant breast cells. Moreover, miR-1246 can suppress the expression level of its target gene, Cyclin-G2 (CCNG2), indicating its functional significance. Finally, treatment with exosomes derived from MDA-MB-231 cells could enhance the viability, migration and chemotherapy resistance of non-malignant HMLE cells. CONCLUSIONS: Together, our results support an important role of exosomes and exosomal miRNAs in regulating breast tumor progression, which highlights their potential for applications in miRNA-based therapeutics.


Assuntos
Ciclina G2/metabolismo , Exossomos/metabolismo , MicroRNAs/metabolismo , Regiões 3' não Traduzidas , Sequência de Bases , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Análise por Conglomerados , Ciclina G2/antagonistas & inibidores , Ciclina G2/genética , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , Células MCF-7 , MicroRNAs/genética , Análise de Sequência com Séries de Oligonucleotídeos , RNA Nuclear Pequeno/metabolismo , Alinhamento de Sequência , Regulação para Cima
15.
Tumour Biol ; 39(2): 1010428317691182, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28231725

RESUMO

Extracellular vesicles have emerged as important mediators of intercellular communication and play an active role in cancer, including breast cancer. Despite limited studies, initial observations suggest that these vesicles are important in breast physiology and pathophysiology. We here, in brief, describe their potential use as future biomarkers and therapeutic agents in breast cancer. Extracellular vesicles in blood and breast fluid may have a great potential to detect and predict the presence of breast cancer, and extracellular vesicles modulation may emerge as a therapeutic approach in cancer therapy.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/patologia , Animais , Neoplasias da Mama/genética , Neoplasias da Mama/terapia , Linhagem Celular Tumoral , Feminino , Terapia Genética/métodos , Humanos , Células MCF-7
16.
Int J Cancer ; 139(11): 2583-92, 2016 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-27537102

RESUMO

Several clinical studies have demonstrated that increased macrophage infiltration into tumors confers metastatic potential and poor prognosis in cancer. Preclinical studies are needed to develop new strategies for countering metastasis. Our study was designed to investigate the impact of pulmonary macrophages on lung metastasis of anaplastic thyroid cancer (ATC). ATC (CAL-62) and macrophage (Raw264.7) were transfected with the effluc (CAL-62/effluc, Raw264.7/effluc). Coculture and migration assays were used to assess the effect of Raw264.7 or THP1 (human macrophage) (or conditioned medium) on the proliferation and/or migration of CAL-62/effluc cells in vitro. The effect of clodro-lipo or PBS-lipo on macrophage depletion was confirmed in vitro and in vivo. CAL-62/effluc cells (1 × 10(6) ) were intravenously injected into nude mice 24 h after clodro-lipo or PBS-lipo administration. Effect of clodro-lipo on the lung metastasis of CAL-62/effluc was assessed by bioluminescence imaging (BLI). Micro computed tomography (micro-CT) and histology. BLI signals of CAL-62/effluc and Raw264.7/effluc increased to cell number. Raw264.7 cells and THP1 cells promoted CAL-62/effluc proliferation, and conditioned medium of Raw264.7 cells promoted CAL-62/effluc migration. Clodro-lipo significantly depleted pulmonary macrophages in vitro and in vivo. Intensity of BLI signals in ATC lung metastasis was weaker in the clodro-lipo group than PBS-lipo control. Micro-CT imaging and hematoxylin/eosin staining revealed smaller tumor masses in the clodro-lipo group than PBS-lipo control. Our findings indicate that pulmonary macrophages have an important role in initiation of lung metastasis of ATC. New therapeutic strategies that preclude initiation of pulmonary metastasis could potentially be developed by targeting pulmonary macrophages.


Assuntos
Neoplasias Pulmonares/secundário , Macrófagos Alveolares/patologia , Carcinoma Anaplásico da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Animais , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Progressão da Doença , Feminino , Genes Reporter , Humanos , Luciferases de Vaga-Lume/análise , Luciferases de Vaga-Lume/biossíntese , Luciferases de Vaga-Lume/genética , Medições Luminescentes/métodos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células RAW 264.7
17.
Curr Opin Oncol ; 27(6): 457-65, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26371779

RESUMO

PURPOSE OF REVIEW: Anthracyclines and taxanes are the two most active classes of cytotoxic agents that are commonly used for the treatment of breast cancer. However, resistance to these agents has become a major clinical obstacle. The aim of the present review is to define the roles of noncoding RNA (ncRNA) in breast cancer progression and the development of chemotherapy resistance. The ultimate goal is to exploit ncRNAs as new therapeutic tools to overcome resistance. RECENT FINDINGS: Two important types of ncRNA include microRNA (miRNA) and long noncoding RNA (lncRNA). Both miRNA and lncRNA have recently impacted the field of breast cancer research as important pieces in the mechanistic puzzle of the genes and pathways involved in breast cancer development and progression. SUMMARY: Herein, we review the roles of miRNA and lncRNA in breast cancer progression and the development of chemotherapy resistance. Future research should include identification of ncRNAs that could be potential therapeutic targets in chemotherapy-resistant tumors, as well as ncRNA biomarkers that facilitate more tumor-specific treatment options for chemotherapy-resistant breast cancer patients.


Assuntos
Antraciclinas/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Resistencia a Medicamentos Antineoplásicos/genética , RNA não Traduzido/fisiologia , Taxoides/uso terapêutico , Antibióticos Antineoplásicos/uso terapêutico , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/fisiologia
18.
J Surg Res ; 193(2): 902-8, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25439504

RESUMO

BACKGROUND: The controversial results from different studies suggested that leukocyte recruitment mediated by leukotriene B4 (LTB4) and its receptor might improve pathogen clearance, but might also aggravate organ injury during sepsis. The present study was performed to compare the effect of BLT1 ligand LTB4 and its antagonist U-75302 on the development of sepsis. METHODS: Sepsis in mice was induced by cecal ligation and puncture (CLP). The mice were allocated into sham group, CLP group, U-75302 group, and LTB4 group. In the latter three groups, CLP mice were treated by intraperitoneal saline, U-75302, and LTB4, respectively. Their effect on the progression of sepsis were compared by histopathologic tests, level of systemic cytokines, counts of immune cells and bacterial clearance, and survival rate. RESULTS: The histopathologic tests showed that U-75302 attenuated lung injury, whereas LTB4 aggravated liver injury. LTB4 increased the plasma levels of interleukin-6, tumor necrosis factor-α, and U-75302 increased the level of plasma interleukin-10. LTB4 increased whereas U-75302 reduced the neutrophil numbers in the peritoneal lavage fluid. LTB4 also increased the number of peritoneal and splenic CD4(+) and CD8(+) T cells. Bacterial clearance in blood and peritoneal lavage fluid was significantly enhanced in the LTB4 group. Both U-75302 and LTB4 did not change the survival rate significantly compared with vehicle, but mortality in the LTB4 group was significantly higher than in the U-75302 group. Dose response analyses were also performed to compare the effect of U-75302 and LTB4 at different doses. Different doses of both agents did not influence the survival rate of CLP mice. CONCLUSIONS: U-75302 attenuates sepsis-induced organ injury, whereas LTB4 increases the leukocyte recruitment toward infection site, but LTB4 showed a more lethal effect than U-75302 during polymicrobial sepsis.


Assuntos
Álcoois Graxos/toxicidade , Glicóis/toxicidade , Leucotrieno B4/toxicidade , Receptores do Leucotrieno B4/metabolismo , Sepse/metabolismo , Animais , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Receptores do Leucotrieno B4/agonistas , Receptores do Leucotrieno B4/antagonistas & inibidores
19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(3): 599-602, 2015 Mar.
Artigo em Zh | MEDLINE | ID: mdl-26117862

RESUMO

To explore the feasibility of quick intraoperative in situ and noninvasive diagnosis of lymph node metastasis in gastric cancer by Fourier transform infrared (FTIR) spectrometry. FTIR spectra of surgically removed fresh lymph nodes were measured by FTIR via probe of attenuated total reflection (ATR). For each spectrum, 13 bands were indentified and assigned between 3 000 and 1 000 cm(-1). Peaks in the spectra were measured and relative intensity ratios were calculated and compared between the spectra of Metastatic lymph nodes (MLN) and Non-metastatic lymph nodes (NMLN). Standard statistic analysis was performed. 720 lymph nodes were measured in 38 gastric cancer patients. Results show that there were significant differences between the FTIR of 540 MLN and 180 NMLN. (1) For the band related to nucleic acid: The ratios of I1240/I1460 (p = 0.015) and I1080/I1460 (p = 0.034) increased in MLN, which shows that the relative quantity of nucleic acid was more in MLN than that in NMLN. (2) For the bands related to protein: The ratios of I1640 /I1460 (p = 0.001) and I146/I1460 (p = 0.027) increased in MLN, which shows that the relative quantity of protein was more in MLN. (3) For the bands related to lipid: The ratio of I2855/I460 and I1740/I1460 decreased in MLN FTIR spectrum, indicating the lower relative quantity of lipid in MLN. (4) For the bands related to carbohydrate: The ratio of I1160/I1460 (p = 0.023) decreased in MLN FTIR spectrum, indicating the lower relative quantity of carbohydrate in MLN. The results demonstrate that the FTIR spectroscopy technique maybe develop into a promising method for in situ and quick intraoperative differential diagnosis of lymph node metastasis in gastric cancer.


Assuntos
Metástase Linfática/diagnóstico , Neoplasias Gástricas/patologia , Carboidratos , Humanos , Lipídeos , Linfonodos/patologia , Ácidos Nucleicos , Proteínas , Espectroscopia de Infravermelho com Transformada de Fourier
20.
Clin Radiol ; 69(9): 965-73, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24984786

RESUMO

AIM: To visualize the segment IV hepatic artery and to evaluate the variations in anatomy using multidetector computed tomography (MDCT) angiography. MATERIALS AND METHODS: Six hundred and seventeen patients (381 men and 236 women; mean age 62.7 ± 8.1 years; age range 22-92 years) who underwent MDCT angiography performed using a 128-section MDCT system were included in the study. The segment IV hepatic arteries of 453 patients with adequate image quality were displayed using volume rendering (VR), maximum intensity projection (MIP), and multiplanar reconstruction (MPR), and were analysed regarding the origination and variation of the arteries by two radiologists and an anatomist retrospectively. RESULTS: Segment IV arteries were categorized into five different types according to their points of origin: left hepatic artery (LHA, 51.66%), right hepatic artery (RHA, 30.68%), proper hepatic artery (PHA, 5.3%), dual (12.14%), and triple (0.22%). Segment IV arteries arising from normal LHA, RHA, and PHA were found in 73.73% of patients, and those arising from variant LHA or RHA were found in 26.27%. The patterns RN2, LA2, LA3, LA4, PN2, PV1, DA1, DA2, DV3, and DV4 were first reported in the present study. CONCLUSIONS: MDCT angiography can evaluate normal as well as anatomical variants of segment IV arteries. Predicting arterial patterns of segment IV of the liver is important in planning and performing all radiological and surgical procedures in the liver, especially in hemi-liver graft procedures.


Assuntos
Angiografia , Artéria Hepática/diagnóstico por imagem , Imageamento Tridimensional , Fígado/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Artéria Hepática/anatomia & histologia , Artéria Hepática/patologia , Humanos , Fígado/anatomia & histologia , Fígado/patologia , Transplante de Fígado/métodos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Estudos Retrospectivos , Sensibilidade e Especificidade
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