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1.
World J Urol ; 42(1): 541, 2024 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-39325194

RESUMO

PURPOSE: The management of renal cell carcinoma (RCC) relies on clinical and histopathological features for treatment decisions. Recently, radiomics, which involves the extraction and analysis of quantitative imaging features, has shown promise in improving RCC management. This review evaluates the current application and limitations of radiomics for predicting treatment and oncological outcomes in RCC. METHODS: A systematic search was conducted in Medline, EMBASE, and Web of Science databases or studies that used radiomics to predict response to treatment and survival outcomes in patients with RCC. The study quality was assessed using the Radiomics Quality Score (RQS) tools. RESULTS: The systematic review identified a total of 27 studies, examining 6,119 patients. The most used imaging modality was contrast-enhanced abdominal CT. The reviewed studies extracted between 19 and 3376 radiomics features, including Histogram, Texture, Filter, or transformation method. Radiomics-based risk stratification models provided valuable insights into treatment response and oncological outcomes. All developed signatures demonstrated at least modest accuracy (AUC range: 0.55-0.99). The studies included in this analysis reported heterogeneous results regarding radiomics methods. The range of Radiomics Quality Score (RQS) was from - 5 to 20, with a mean RQS total of 9.15 ± 7.95. CONCLUSION: Radiomics has emerged as a promising tool in the management of RCC. It offers the potential for improved risk stratification and response assessment. However, future trials must demonstrate the generalizability of findings to prospective cohorts before progressing towards clinical translation.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Humanos , Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/terapia , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/mortalidade , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/terapia , Neoplasias Renais/patologia , Neoplasias Renais/mortalidade , Resultado do Tratamento , Taxa de Sobrevida , Prognóstico , Valor Preditivo dos Testes , Tomografia Computadorizada por Raios X , Radiômica
2.
Sci Total Environ ; 951: 175524, 2024 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-39155007

RESUMO

Cyclic methylsiloxanes (CMSs), widely found in wastewater treatment plants (WWTPs), are potentially hazardous to the environment and human health. In this study, the environmental behavior and human exposure risks of three CMSs (D4-D6) were evaluated in WWTPs located in Beijing and Kunming, Yunnan province. D5 had the highest concentrations in air, water, and sludge, with seasonal variation that consisted of a high concentration in summer and low concentration in winter. The CMS concentrations in air were 3-4-fold higher in the A2/O (Anaerobic-Anoxic-Oxic) treatment units than in the other units. CMS emissions to air, soil, and water from the Beijing WWTP were in the ranges of 3.4 × 104-5.0 × 104 kg·a-1, 4.5 × 102-7.5 × 102 kg·a-1, and 2.5 × 102-2.9 × 102 kg·a-1, constituting 98 %, 1.3 %, and 0.7 % of the total emissions, respectively. Total daily inhalation exposure doses of CMSs (ADDinh,CMSs) associated with four different jobs in WWTPs showed that wastewater treatment technicians had the highest ADDinh,CMSs (51 µg/kg/day), indicating that these people had the highest occupational exposure risk in WWTPs. Therefore, this study identified that atmospheric emission was the main environmental fate of CMSs in WWTPs, and provide a basis for the improvement of WWTP process and risk management decisions. ENVIRONMENTAL IMPLICATION: Assessing the environmental fate and occupational exposure risk of cyclic methylsiloxanes (CMSs) found in wastewater treatment plants (WWTPs) is crucial. This is the first study to identify that atmospheric emission was the main environmental fate of CMSs in WWTPs, especially D5; the inhalation exposure doses of CMSs were all significantly higher in the occupational population working in WWTPs. The results described in our study will help enhance the understanding of current knowledge base of environmental fate and exposure risk of CMSs in WWTPs, and provide a basis for the improvement of WWTP process and risk management decisions.


Assuntos
Monitoramento Ambiental , Exposição Ocupacional , Eliminação de Resíduos Líquidos , Águas Residuárias , Exposição Ocupacional/análise , Exposição Ocupacional/estatística & dados numéricos , Águas Residuárias/química , Siloxanas/análise , Humanos , China , Poluentes Químicos da Água/análise , Pequim
3.
BMC Gastroenterol ; 23(1): 385, 2023 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-37950156

RESUMO

Several studies have shown significant involvement of tumor-associated macrophages (TAMs) in the tumor microenvironment and cancer progression. However, no data on reliable TAM-related biomarkers are available for predicting the prognosis of patients with colorectal cancer (CRC). We analyzed the clinical data and gene expression profiles of patients with CRC from databases. The single-cell transcriptomic data was applied to identify M2-like TAM-related differentially expressed genes. Univariate Cox and least absolute shrinkage and selection operator regression analyses were used to determine the prognostic signature genes. Then, seven key genes were screened to develop the prognostic signature. In the training and external validation cohorts, the overall survival (OS) of patients in the high-risk group was significantly shorter compared to the low-risk group. Consequently, we created a nomogram that could accurately and reliably predict the prognosis of patient with CRC. A significant correlation was observed between the patient's prognosis, clinical features, sensitivity to anticancer drugs, TME, and risk scores. Moreover, risk score was strongly related to the response to immunotherapy in patients from GSE91061, GSE78220, and GSE60331 cohorts. Finally, high expression of HSPA1A, SERPINA1, CXCL1, and low expression of DNASE1L3 were found in human CRC tissue and normal tissue by using qRT-PCR. In conclusion, the M2-like TAM-related prognostic signature could predict the survival, prognosis, and response of patients with CRC to immunotherapy, which sheds light on the role of TAMs in CRCs and enhances our understanding of TAMs.


Assuntos
Neoplasias Colorretais , Macrófagos Associados a Tumor , Humanos , Prognóstico , Nomogramas , Bases de Dados Factuais , Neoplasias Colorretais/genética , Microambiente Tumoral/genética
4.
BMJ Open ; 13(10): e075023, 2023 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-37798027

RESUMO

INTRODUCTION: Organ preservation is now considered an acceptable alternative option in distal rectal cancer patients with clinical complete response (cCR) after neoadjuvant chemoradiation (CRT). But the cCR rate is low and about one-third of tumour will regrow, which requires more effective local treatment. CRT combined with intra-arterial chemotherapy (IAC) might be a promising approach. Additionally, total neoadjuvant therapy using FOLFIRINOX induction chemotherapy improved survival while consolidation chemotherapy improved organ preservation. We assess whether IAC plus CRT and FOLFIRINOX consolidation chemotherapy can improve the chance of organ preservation and survival in distal rectal cancer. METHODS AND ANALYSIS: This prospective, monocentric, open-label, single-arm phase II study will include 32 patients with cT3-4NanyM0 distal rectal adenocarcinoma. All patients will receive one cycle of IAC (irinotecan, raltitrexed and oxaliplatin), followed by CRT (50 Gy/25 fractions with concomitant capecitabine) and then with six cycles of FOLFIRINOX (leucovorin, 5-fluorouracil, oxaliplatin and irinotecan). After final evaluation, patients with cCR will receive non-operative management or surgery at their own discretion and others are mandatorily referred to surgery. Adjuvant chemotherapy with six cycles of mFOLFOX6 (leucovorin, 5-fluorouracil and oxaliplatin) will be used for patients with adverse pathological features. The primary endpoint is the rate of complete response (CR; pathological CR or sustained cCR≥2 years). The main secondary endpoints are toxicity, compliance, short-term and long-term oncological outcomes, surgical morbidity and quality of life. This protocol has been designed in accordance with the Standard Protocol Items: Recommendations for Interventional Trials 2013 guidelines. ETHICS AND DISSEMINATION: This study was approved by the Academic and Ethics Committee of The Affiliated Hospital of Youjiang Medical University for Nationalities in March 2023. Trial results will be published in peer-reviewed international journals and on the ChiCTR website. PROTOCOL VERSION: Registered on 18 April 2023; version #1. TRIAL REGISTRATION NUMBER: ChiCTR2300070620.


Assuntos
Neoplasias Pancreáticas , Neoplasias Retais , Humanos , Terapia Neoadjuvante/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Irinotecano/uso terapêutico , Oxaliplatina/uso terapêutico , Leucovorina/uso terapêutico , Qualidade de Vida , Estudos Prospectivos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/patologia , Fluoruracila/uso terapêutico , Quimiorradioterapia/métodos , Estadiamento de Neoplasias , Ensaios Clínicos Fase II como Assunto
5.
Front Genet ; 12: 654686, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34249085

RESUMO

Long noncoding RNA (lncRNA) have been reported to be crucial regulators for carcinogenesis, including rectal cancer. This work aimed to explore the roles and associated mechanisms of small nucleolar RNA host gene 17 (SNHG17) in rectal cancer. A quantitative real-time polymerase chain reaction was performed to measure the expression level of SNHG17 in rectal cancer tissues and cells. Cell counting kit-8 (CCK-8) assay and flow cytometry assay were conducted to measure the biological roles of SNHG17 in rectal cancer. In addition, luciferase activity reporter assay, RNA immunoprecipitation (RIP) assay, and rescue experiments were conducted to explore the mechanisms of SNHG17 in rectal cancer. The upregulation status of SNHG17 was identified in rectal cancer tissues and cells. Functionally, knockdown the expression of SNHG17 inhibits rectal cancer cell proliferation via stimulating cell apoptosis. In vivo assay showed that the knockdown of SNHG17 inhibits tumor growth. Furthermore, we showed that microRNA-361-3p (miR-361-3p) has decreased expression in tumor tissues and cells, and SNHG17 functions as a sponge for miR-361-3p. The upregulation status of stanniocalcin 2 (STC2) was also found in rectal cancer, and the knockdown of STC2 hinders cancer progression. In conclusion, lncRNA SNHG17 functions as an oncogenic lncRNA in rectal cancer by regulating the miR-361-3p/STC2 axis.

6.
Clin Cancer Res ; 27(17): 4794-4806, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34210685

RESUMO

PURPOSE: Intratumoral heterogeneity (ITH) challenges the molecular characterization of clear cell renal cell carcinoma (ccRCC) and is a confounding factor for therapy selection. Most approaches to evaluate ITH are limited by two-dimensional ex vivo tissue analyses. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) can noninvasively assess the spatial landscape of entire tumors in their natural milieu. To assess the potential of DCE-MRI, we developed a vertically integrated radiogenomics colocalization approach for multi-region tissue acquisition and analyses. We investigated the potential of spatial imaging features to predict molecular subtypes using histopathologic and transcriptome correlatives. EXPERIMENTAL DESIGN: We report the results of a prospective study of 49 patients with ccRCC who underwent DCE-MRI prior to nephrectomy. Surgical specimens were sectioned to match the MRI acquisition plane. RNA sequencing data from multi-region tumor sampling (80 samples) were correlated with percent enhancement on DCE-MRI in spatially colocalized regions of the tumor. Independently, we evaluated clinical applicability of our findings in 19 patients with metastatic RCC (39 metastases) treated with first-line antiangiogenic drugs or checkpoint inhibitors. RESULTS: DCE-MRI identified tumor features associated with angiogenesis and inflammation, which differed within and across tumors, and likely contribute to the efficacy of antiangiogenic drugs and immunotherapies. Our vertically integrated analyses show that angiogenesis and inflammation frequently coexist and spatially anti-correlate in the same tumor. Furthermore, MRI contrast enhancement identifies phenotypes with better response to antiangiogenic therapy among patients with metastatic RCC. CONCLUSIONS: These findings have important implications for decision models based on biopsy samples and highlight the potential of more comprehensive imaging-based approaches.


Assuntos
Carcinoma de Células Renais/diagnóstico por imagem , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Neoplasias Renais/diagnóstico por imagem , Neoplasias Renais/genética , Neoplasias Renais/patologia , Imageamento por Ressonância Magnética/métodos , Genômica por Radiação , Microambiente Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Inibidores da Angiogênese/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Feminino , Humanos , Neoplasias Renais/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
7.
Sci Total Environ ; 751: 142027, 2021 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-33182009

RESUMO

Despite their profound roles in atmospheric chemistry and health concerns, the gas-particle partitioning of carbonyl compounds and its influencing factors in the ambient atmosphere are poorly elucidated. In this work, a reliable method using a denuder/filter-pack system coated with the derivative reagent, O-(2,3,4,5,6-pentafluorobenzyl)hydroxylamine (PFBHA) was developed for the simultaneous collection of gaseous and particulate carbonyls. Sampling campaigns were performed at an urban site in Zhengzhou, China. The average field-derived partitioning coefficients (Kpf) of the six most abundant carbonyls (formaldehyde, acetaldehyde, acetone, propionaldehyde, glyoxal, and methylglyoxal) were in the range of 10-5-10-4 m3·µg-1, and their effective Henry's law coefficients (eff. KH) ranged from 107 to 109 M·atm-1. Comparisons revealed that their Kpf and eff. KH were 104-106 times and 102-107 times higher than theoretically predicted, respectively. Given that the aerosol liquid water is a concentrated salt solution, these six carbonyls very clearly salted in to three atmospherically relevant aqueous salts, following the order of sulfate > ammonium > nitrate. However, even taking salting-in effects into account, the Pankow's absorptive partitioning theory and effective Henry's law both failed to explain the unexpected highly particulate carbonyls. In regard to the influencing factors, the negative correlations between Kpf and temperature indicate that lower temperature is conducive to carbonyls partitioning. As for the strong relative humidity (RH) dependence of KPf, high partitioning coefficients were observed under low and high RH conditions. Partitioning is considered to be dominated by the carbonyl-oligomer formation when RH increases from <10% to 50%, and driven by the abundant aerosol liquid water content when RH exceeds 50%. The presence of particulate inorganic components and the transition of particle phase state may also impact the partitioning process, especially in the urban atmosphere.

8.
ACS Sens ; 5(10): 3082-3090, 2020 10 23.
Artigo em Inglês | MEDLINE | ID: mdl-32786388

RESUMO

In this work, we demonstrate a multifunctional, portable, and disposable microfluidic device for blood typing and primary screening of blood diseases. Preloaded antibodies (anti-A, anti-B, and anti-D) interact with injected whole blood cells to cause an agglutination reaction that blocks a microslit in the microfluidic channel to accumulate red blood cells and form a visible red line that can be easily read to determine the blood type. Moreover, the different blood density and agglutination properties of normal and subtype blood groups, as well as different blood diseases, including anemia and polycythemia vera, generate different lengths of blood agglutination within the channels, which allows us to successfully screen these various conditions in as little as 2 min. The required blood volume for each test is just 1 µL, which can be obtained by minimally invasive finger pricking. This novel method of observing agglutinated red blood cells to distinguish blood types and diseases is both feasible and affordable, suggesting its promise for use in areas with limited resources.


Assuntos
Tipagem e Reações Cruzadas Sanguíneas , Doenças Hematológicas , Aglutinação , Humanos , Dispositivos Lab-On-A-Chip , Microfluídica
9.
Mol Biol Rep ; 47(1): 141-149, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31583569

RESUMO

In the precedent research conducted by the same team, it concluded that the activities in C-type natriuretic peptide (CNP)/cyclic guanosine monophosphate (cGMP)/cyclic adenosine monophosphate (cAMP)/ß-type phospholipase C (PLCß) pathways of rat antral smooth muscle were changed due to diabetes, which was the key pathogenetic mechanism for diabetic gastric dysmotility. As the follow-on step, this study was designed to probe into the downstream signaling pathway of CNP/PLCß. The results showed that level of α-type protein kinase C (PKCα),cell membrane to cytoplasm ratio of PKCα, cell membrane to cytoplasmic ratio of ßI-type protein kinase C (PKCßI) and level of Phosphor-PKCα (P-PKCα) were significantly reduced in diabetes rat antral smooth muscle samples. The content of tetraphosphate inositol (IP4) in gastric antral smooth muscle of diabetic rats reduced, and the content of diacyl-glycerol (DG) was unchanged. CNP significantly decreased the content of IP4 and DG, this effect was more obvious in diabetic rats. Subsequent to the addition of protein kinase A (PKA) blocker N-[2- (p-Bromocin-namylamino)ethyl]-5 -isoquinolinesulfonamide dihydrochloride (H-89) before CNP treatment, the inhibitory effect of CNP was reduced; subsequent to the addition of protein kinase G (PKG) blocker KT5823 before CNP treatment, the inhibitory effect of CNP was also reduced. With the addition of the combination of H-89 and KT5823 before CNP treatment, the inhibition by CNP could be offset. These results were concluded that CNP inhibited the activity of PKC family in rat smooth muscle and reduced the levels of IP4 and DG through the PKG/PKA-PLCß pathways, causing inhibited muscular contractions, which may be a key pathogenetic factor for diabetic gastroparesis.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Diglicerídeos/metabolismo , Gastroparesia/metabolismo , Fosfatos de Inositol/metabolismo , Peptídeo Natriurético Tipo C/farmacologia , Proteína Quinase C/metabolismo , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Motilidade Gastrointestinal/efeitos dos fármacos , Gastroparesia/etiologia , Gastroparesia/patologia , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Músculo Liso/patologia , Músculo Liso/fisiologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos
10.
Biosci Rep ; 39(7)2019 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-31189744

RESUMO

Laryngeal carcinoma is one of the most common malignant tumors of the head, neck, and respiratory tract. The aim of the present study is to explore the biological function of SRY-related HMG-box 18 (SOX18) in laryngeal carcinoma cells and study the molecular mechanism involved. Initial findings indicate that the expression of SOX18 was increased in laryngeal carcinoma cell lines and tissues. The effect of SOX18 on laryngeal carcinoma cell proliferation, cell cycle, apoptosis, invasion, and migration was also identified. The results indicated that down-regulation of SOX18 significantly inhibited cell proliferation, migration, and invasion, and induced cell-cycle arrest in G0/G1 phase and apoptosis of laryngeal carcinoma cells. However, overexpression of SOX18 promoted cell proliferation, invasion, and migration, and inhibited cell apoptosis. The expression of cyclin D1, active-caspase-3, N-cadherin, MTA1, MMP-2, and MMP-7 was also regulated by the overexpression of siSOX18 or SOX18. In addition, it was found that SOX18 could also accelerate the phosphorylation of JAK2/STAT3 signaling in laryngeal carcinoma cells. Furthermore, our study indicated that SOX18 could stimulate cell proliferation, migration, and invasion of laryngeal carcinoma cells via regulation of JAK2/STAT3 signaling, which could provide a new strategy for laryngeal carcinoma diagnosis and molecular therapies.


Assuntos
Carcinoma/genética , Janus Quinase 2/genética , Neoplasias Laríngeas/genética , Fatores de Transcrição SOXF/genética , Fator de Transcrição STAT3/genética , Apoptose/genética , Carcinoma/patologia , Ciclo Celular/genética , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Neoplasias Laríngeas/patologia , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Transdução de Sinais/genética
11.
PLoS One ; 14(5): e0216554, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31071157

RESUMO

Microstructural asymmetry of the brain can provide more direct causal explanations of functional lateralization than can macrostructural asymmetry. We performed a cross-sectional diffusion imaging study of 314 patients treated for childhood acute lymphoblastic leukemia (ALL) at a single institution and 92 healthy controls. An asymmetry index based on diffusion metrics was computed to quantify brain microstructural asymmetry. The effects of age and the asymmetry metrics of the two cohorts were examined with t-tests and linear models. We discovered two new types of microstructural asymmetry. Myelin-related asymmetry in controls was prominent in the back brain (89% right), whereas axon-related asymmetry occurred in the front brain (67% left) and back brain (88% right). These asymmetries indicate that white matter is more mature and more myelinated in the left back brain, potentially explaining the leftward lateralization of language and visual functions. The asymmetries increase throughout childhood and adolescence (P = 0.04) but were significantly less in patients treated for ALL (P<0.01), especially in younger patients. Our results indicate that atypical brain development may appear long before patients treated with chemotherapy become symptomatic.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Encéfalo/patologia , Imagem de Tensor de Difusão/métodos , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Adolescente , Adulto , Encéfalo/efeitos dos fármacos , Estudos de Casos e Controles , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Processamento de Imagem Assistida por Computador , Lactente , Masculino , Prognóstico , Adulto Jovem
12.
Cell Biochem Biophys ; 77(2): 165-177, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30968342

RESUMO

This study aimed to investigate the effect of AMPK on apoptosis and energy metabolism of gastric smooth muscle cells in diabetic rats and to explore the role of AMPK in the pathogenesis of diabetic gastroparesis (DGP). After establishment of a diabetic rat model, rats were divided into normal control (NC), 4-week (DM4W), 6-week (DM6W), and 8-week (DM8W) diabetic model groups. The gastric residual pigment ratio, intestinal transit rate, and intestinal propulsion rate in each group were detected to confirm the successful establishment of the DGP model. The spontaneous contraction in isolated gastric smooth muscle strips of the NC and DM8W groups was experimentally observed. The expression of phospho-AMPK, AMPK, phospho-LKB1, LKB1, phospho-TAK1, TAK1, and CaMMKß in rat gastric smooth muscle tissues was detected by western blot analysis; ADP, AMP, ATP contents, and the energy charge were detected using Elisa; and apoptosis of gastric smooth muscle cells was detected by flow cytometry. The rat gastric smooth muscle cells were cultured in vitro, and treated with an AMPK inhibitor and an agonist. At 24 and 48 h, the effects of AMPK on apoptosis and energy metabolism of gastric smooth muscle cells were observed. Reduced spontaneous contractions, AMPK activation, cell apoptosis, and energy metabolism disorders were observed in gastric smooth muscle tissues of a diabetic rat, and AMPK activation was associated with an increased ratio of ADP/ATP, AMP/ATP, LKB1 activity, and CaMMKß expression. From in vitro cell culture experiments, we found that AMPK activation of high-glucose conditions promoted cell apoptosis. Inhibition of AMPK had no obvious effect on apoptosis at the early stage with high glucose, but the inhibitory effect was significant at the late stage with high glucose. AMPK can regulate both mitochondrial metabolism and glycolysis pathways under high-glucose conditions. During the early stage with high glucose, AMPK was the main promotion factor of the mitochondrial metabolism pathway, but did not increase the ATP production, AMPK also promoted the glycolysis pathway. During the late stage with high glucose, AMPK was a major inhibitor of the mitochondrial pathway, and still played a role in promoting the glycolytic pathway, which acted as the main regulator. Apoptosis and energy metabolism disorders were present in gastric smooth muscle cells during the occurrence of DGP. Under high-glucose condition, AMPK was activated, which can promote apoptosis, change the energetic metabolism pathway of cells, inhibit mitochondrial energy metabolism, and promote glycolysis.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Apoptose , Gastroparesia/patologia , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/química , Trifosfato de Adenosina/análise , Animais , Apoptose/efeitos dos fármacos , Glicemia/análise , Proteína Quinase Tipo 2 Dependente de Cálcio-Calmodulina/metabolismo , Células Cultivadas , Desoxiglucose/farmacologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Modelos Animais de Doenças , Metabolismo Energético/efeitos dos fármacos , Gastroparesia/etiologia , Gastroparesia/metabolismo , Glicólise/efeitos dos fármacos , MAP Quinase Quinase Quinases/metabolismo , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Miócitos de Músculo Liso/citologia , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Ratos , Ratos Sprague-Dawley
14.
Peptides ; 110: 47-55, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30391424

RESUMO

Our previous work demonstrated that the C-type natriuretic peptide (CNP)/cyclic guanosine monophosphate (cGMP)/cyclic adenosine monophosphate (cAMP) pathway in gastric antrum smooth muscle of rats with diabetes was upregulated and played an important role in the development of diabetic gastric dysmotility. Our goal for this study was to explore the downstream signaling pathways of CNP. We found that the expressions of protein kinase G (PKG) and protein kinase A (PKA) in gastric smooth muscle tissue of rats with diabetes were significantly upregulated. The expressions of ß-type phospholipase C 3(PLCß3) and ß-type phospholipase C 1(PLCß1) protein were reduced, whereas Phosphor-PLCß3Ser1105 (P-PLCß3Ser1105) was increased. The inhibitory effect of CNP on gastric antral smooth muscle in diabetic rats was significantly greater than in the normal group. The content of trisphosphate inositol (IP3) in the gastric antral smooth muscle of rats with diabetes was significantly lower than that of the normal group. After blocking PKA with N-[2-(p-Bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide dihydrochloride (H-89, a blockage PKA), the effect of CNP on the production of IP3 was decreased, while blocking PKG with KT5823 (a blockage PKG) simultaneously, and CNP can no longer reduce the IP3 production. CNP promoted the phosphorylation of PLCß3Ser1105, thereby inhibiting the activity of PLCß3 in gastric smooth muscle tissue of rats with diabetes; this effect can be abolished by blocking PKA and PKG. These results suggested that CNP can decrease IP3 level in gastric smooth muscle cells and thus inhibit gastric smooth muscle contraction through PKG/PKA-PLCß pathway, which may play an important role in the development of diabetic gastroparesis.


Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de GMP Cíclico/metabolismo , Diabetes Mellitus Experimental/complicações , Gastroenteropatias/etiologia , Gastroenteropatias/metabolismo , Motilidade Gastrointestinal/fisiologia , Peptídeo Natriurético Tipo C/metabolismo , Fosfolipase C beta/metabolismo , Animais , Ensaio de Imunoadsorção Enzimática , Feminino , Imuno-Histoquímica , Masculino , Ratos
15.
J Nucl Med ; 59(1): 25-30, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28611244

RESUMO

The purpose of this study was to determine the relationship of 18F-FDG uptake in the primary tumor at diagnosis, during therapy, and after therapy with a histologic response and event-free survival in pediatric and young adult patients with osteosarcoma (OS). Methods: Serial (baseline and 5 and 10 wk after start of therapy) 18F-FDG PET/CT imaging was performed in patients with newly diagnosed OS treated uniformly in a therapeutic trial at a single institution. Whole-body images were obtained approximately 1 h after injection of 18F-FDG. Logistic regression was used to study the association of tumor uptake and changes in SUVmax between 0, 5, and 10 wk for both clinical endpoints. Results: Thirty-four patients (17 males; median age, 12.2 y; age range, 6.8-19.1 y) underwent PET imaging; 25 (74%) had localized disease. Primary tumor locations included the femur (n = 17; 50%), tibia (n = 9; 26%), and humerus (n = 5; 15%). Logistic regression showed that SUVmax at 5 wk (P = 0.034) and 10 wk (P = 0.022) and percentage change from baseline at 10 wk (P = 0.021) were highly predictive of a histologic response. Using SUVmax of 4.04 at week 5, SUVmax of 3.15 at week 10, and 60% decrease from baseline at week 10 as cutoff values, we determined that the respective sensitivities were 0.93, 0.93, and 0.79 and that the respective specificities were 0.53, 0.71, and 0.76. Conclusion: SUVmax on routine images at 5 or 10 wk and percentage change in SUVmax from baseline to week 10 were metabolic predictors of a histologic response in OS. These findings may be useful in the early identification of patients who are responding poorly to therapy and may benefit from a change in treatment.


Assuntos
Quimioterapia Adjuvante , Fluordesoxiglucose F18/metabolismo , Osteossarcoma/tratamento farmacológico , Osteossarcoma/metabolismo , Adolescente , Adulto , Transporte Biológico , Criança , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Fatores de Tempo
16.
Mol Med Rep ; 16(2): 1779-1784, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28656252

RESUMO

The authors previously demonstrated that unconjugated bilirubin (UCB) may inhibit the activities of various digestive proteases, including trypsin and chymotrypsin. The digestive proteases in the lower gut are important in the pathogenesis of inflammatory bowel diseases. The effects of UCB on the inflammation and levels of digestive proteases in feces of rats with colitis have not yet been revealed. The present study investigated the effect of UCB on the inflammatory status and levels of trypsin and chymotrypsin in the feces of rats with trinitrobenzenesulfonic acid (TNBS)­induced colitis. The data indicated that treatment with TNBS resulted in a marked reduction in weight gain, which was significantly alleviated in UCB­treated rats. Furthermore, UCB treatment alleviated the inflammation induced by TNBS, detected via macroscopic damage and microscopic inflammation scores, and pro­inflammatory markers including myeloperoxidase (MPO), tumor necrosis factor (TNF)­α and interleukin (IL)­1ß. Furthermore, rats with colitis demonstrated significant increases in fecal trypsin and chymotrypsin levels, whereas UCB treatment significantly alleviated these increases. A significant positive correlation was additionally revealed among the pro­inflammatory markers (MPO, TNF­α and IL­1ß) and fecal digestive proteases (trypsin and chymotrypsin) in colitis. The results of the present study demonstrated that UCB ameliorated the inflammation and digestive protease increase in TNBS-induced colitis.


Assuntos
Bilirrubina/uso terapêutico , Colite/tratamento farmacológico , Colite/enzimologia , Endopeptidases/metabolismo , Inflamação/tratamento farmacológico , Inflamação/enzimologia , Animais , Bilirrubina/farmacologia , Biomarcadores/metabolismo , Quimotripsina/metabolismo , Colite/induzido quimicamente , Colite/patologia , Colo/patologia , Citocinas/metabolismo , Digestão/efeitos dos fármacos , Fezes , Inflamação/patologia , Mediadores da Inflamação/metabolismo , Masculino , Ratos Sprague-Dawley , Ácido Trinitrobenzenossulfônico , Tripsina/metabolismo , Redução de Peso/efeitos dos fármacos
17.
Environ Pollut ; 225: 175-183, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28371732

RESUMO

Trifluoroacetic acid (TFA) in the atmosphere is produced by degradation of hydrochlorofluorocarbons and hydrofluorocarbons. In recent years, TFA has attracted global attention because of increased environmental concentrations, biological toxicity and accumulation in aqueous environments. This study focused on the mechanisms underlying the adsorption of TFA by particulate matter to identify the appropriate descriptive model for this process and thus improve estimation of TFA adsorption in future environmental monitoring. Onsite gas and particle phase sampling in Beijing, China, and subsequent measurement of TFA concentrations indicated that the TFA concentration in the gas phase (1396 ± 225 pg m-3) was much higher than that in the particle phase (62 ± 8 pg m-3) and that monthly concentrations varied seasonally with temperature. Based on the field results and analysis, an adsorption experiment of TFA on soot was then conducted at three different temperatures (293, 303, and 313 K) to provide parameters for kinetic and thermodynamic modelling. The proportion of atmospheric TFA concentration in the gas phase increased with temperature, indicating that temperature affected the phase distribution of TFA. The subsequent kinetic and thermodynamic modelling showed that the adsorption of TFA by soot could be described well by the Bangham kinetic model. The adsorption was controlled by diffusion, and the key mechanism was physical adsorption. The adsorption behavior can be well described by the Langmuir isotherm model. The calculated thermodynamic parameters ΔG° (-2.34, -1.25, and -0.15 kJ mol-1 at 293, 303, and 313 K, respectively), ΔH° (-34.34 kJ mol-1), and ΔS° (-109.22 J mol-1 K-1) for TFA adsorption by soot were negative, indicating that adsorption was a spontaneous, exothermic process.


Assuntos
Modelos Químicos , Ácido Trifluoracético/química , Poluentes Químicos da Água/química , Adsorção , Pequim , China , Monitoramento Ambiental , Substâncias Húmicas , Concentração de Íons de Hidrogênio , Cinética , Material Particulado , Fuligem , Temperatura , Termodinâmica
18.
AJR Am J Roentgenol ; 206(5): 933-9, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26999488

RESUMO

OBJECTIVE: The purpose of this study was to investigate contrast-enhanced ultrasound assessment of tumor response to antiangiogenic therapy in children and adolescents with solid malignancies. SUBJECTS AND METHODS: Children with recurrent solid tumors who were enrolled in an institutional phase 1 study of antiangiogenic therapy underwent contrast-enhanced ultrasound of target lesions before therapy, on therapy days 3 and 7, and at the end of course 1. Acoustic data from target lesion ROIs were used to measure peak enhancement, time to peak, rate of enhancement, total AUC, AUC during wash-in (AUC1), and AUC during washout (AUC2). The Cox regression model was used to assess the association between changes in parameters from baseline to follow-up time points and time to tumor progression. Values of p ≤ 0.050 were considered significant. RESULTS: Target lesion sites included liver (n = 3), pleura (n = 2), and supraclavicular mass, soft-tissue component of bone metastasis, lung, retroperitoneum, peritoneum, lymph node, muscle mass, and perineum (n = 1 each). Hazard ratios for changes from baseline to end of course 1 for peak enhancement (1.17, p = 0.034), rate of enhancement (3.25, p = 0.029), and AUC1 (1.02, p = 0.040) were significantly associated with time to progression. Greater decreases in these parameters correlated with longer time to progression. CONCLUSION: Contrast-enhanced ultrasound measurements of tumor peak enhancement, rate of enhancement, and AUC1 were early predictors of time to progression in a cohort of children and adolescents with recurrent solid tumors treated with antiangiogenic therapy. Further investigation of these findings in a larger population is warranted.


Assuntos
Inibidores da Angiogênese/uso terapêutico , Neoplasias/diagnóstico por imagem , Adolescente , Criança , Pré-Escolar , Meios de Contraste , Feminino , Humanos , Lactente , Masculino , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/tratamento farmacológico , Recidiva Local de Neoplasia/patologia , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Projetos Piloto , Indução de Remissão , Ultrassonografia , Adulto Jovem
19.
Artigo em Chinês | MEDLINE | ID: mdl-26930908

RESUMO

OBJECTIVE: To evaluate the effectiveness of glucocorticoid in the management of olfaction in patients with chronic rhinosinusitis accompanied with nasal polyposis. METHOD: The published studies of the effectiveness of glucocorticoid in the management of chronic rhinosinusitis with nasal polyposis were searched in the Medline, Cochrane, EMBASE, Springer and CNKI databases(from the date of establishment of the databases to December 2014). The trails selection based on inclusion criteria and the quality of the included studies was assessed and meta-analysis was performed with RevMan 5. 3 software. RESULT: A total of 5 trials involving 325 patients were included. The Meta-analysis showed that oral glucocorticoid showed more significant improvement in subjective olfaction scores compared to placebo [SMD = -2.22, 95% CI (-3.94 - -0. 49), P < 0.05], oral glucocorticoid also showed significant improvement in objective olfaction scores compared to placebo [SMD = 0.65, 95% CI (0.28-1.01), P < 0.05]. But subsequent use of nasal glucocorticoid had no impact on subjective and objective olfaction scores [SMD = -2.15, 95% CI (-5.67-1.38), P > 0.05], [SMD = 0.28, 95% CI (-0.08-0.64) P > 0.05]. CONCLUSION: According to current evidence, oral glucocorticoid can significantly improve subjective and objective olfaction among patients with CRSwNP, but nasal glucocorticoid cannot improve subjective or objective olfaction dysfunction.


Assuntos
Glucocorticoides/uso terapêutico , Pólipos Nasais/tratamento farmacológico , Sinusite/tratamento farmacológico , Olfato/efeitos dos fármacos , Doença Crônica , Ensaios Clínicos como Assunto , Humanos , Pólipos Nasais/complicações , Sinusite/complicações
20.
Zhonghua Wei Chang Wai Ke Za Zhi ; 15(4): 400-3, 2012 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-22539392

RESUMO

OBJECTIVE: To investigate single nucleotide polymorphisms(SNPs) and haplotypes of interleukin-18(IL-18) gene associated with the susceptibility to colorectal cancer(CRC). METHODS: Two SNPs of IL-18 gene promoter -137G/C and -607C/A in 170 patients with CRC and 160 healthy controls matched by age and sex in a Chinese population were analyzed using polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP) strategy. Frequency of haplotypes and linkage disequilibrium of IL-18 gene in different groups were analyzed by SHEsis programs. RESULTS: The distributions of IL-18 gene -607C/A polymorphism did not differ between CRC patients and healthy controls, but IL-18 gene -137G/C polymorphism was significantly different(P<0.05). The relative risk of C allele for CRC was 1.814 times of the G allele (OR=1.814,95% CI:1.246-2.642). Consistent with the results of the genotyping analyses, IL-18 -137G/C and -607C/A polymorphisms showed strong linkage disequilibrium(|D'|=0.945), frequency of the -137C/-607A haplotype in patients with CRC was significantly higher than that in healthy controls(P<0.05). The -137C/-607A haplotype was associated with a significantly increased risk of CRC(OR=1.637, 95% CI:1.100-2.437). CONCLUSIONS: IL-18 gene -137G/C polymorphism and -137C/-607A haplotype are associated with CRC. -137C allele may be an important genetic susceptibility gene for CRC.


Assuntos
Neoplasias Colorretais/genética , Predisposição Genética para Doença , Interleucina-18/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Feminino , Haplótipos , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição
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