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1.
Cell Mol Biol Lett ; 29(1): 24, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317065

RESUMO

BACKGROUND: Chronic nonhealing wounds remain a considerable challenge in clinical treatment due to excessive inflammation and impeded reepithelialization and angiogenesis. Therefore, the discovery of novel prohealing agents for chronic skin wounds are urgent and important. Amphibian-derived prohealing peptides, especially immunomodulatory peptides, provide a promising strategy for the treatment of chronic skin trauma. However, the mechanism of immunomodulatory peptides accelerating the skin wound healing remains poorly understood. METHODS: The prohealing ability of peptide Andersonin-W1 (AW1) was assessed by cell scratch, cell proliferation, transwell, and tube formation. Next, full-thickness, deep second-degree burns and diabetic full-thickness skin wounds in mice were performed to detect the therapeutic effects of AW1. Moreover, the tissue regeneration and expression of inflammatory cytokines were evaluated by hematoxylin and eosin (H&E), enzyme-linked immunosorbent assay (ELISA), and immunohistochemistry staining. Molecular docking, colocalization, and western blotting were used to explore the mechanism of AW1 in promoting wound healing. RESULTS: We provide solid evidence to display excellent prohealing effects of AW1, identified as a short antimicrobial peptide in our previous report. At relative low concentration of nM, AW1 promoted the proliferation, migration, and scratch repair of keratinocyte, macrophage proliferation, and tube formation of HUVEC. AW1 also facilitated reepithelialization, granulation regeneration, and angiogenesis, thus significantly boosting the healing of full-thickness, deep second-degree burns and diabetic skin wounds in mice. Mechanistically, in macrophages, AW1 directly bound to Toll-like receptor 4 (TLR4) in the extracellular region and regulated the downstream nuclear factor-κB (NF-κB) signaling pathway to facilitate the inflammatory factor secretion and suppress excessive inflammation induced by lipopolysaccharide (LPS). Moreover, AW1 regulated macrophage polarization to promote the transition from the inflammatory to the proliferative phase and then facilitated reepithelialization, granulation regeneration, and angiogenesis, thus exhibiting excellent therapeutic effects on diabetic skin wounds. CONCLUSIONS: AW1 modulates inflammation and the wound healing process by the TLR4/NF-κB molecular axis, thus facilitating reepithelialization, granulation regeneration, and angiogenesis. These findings not only provided a promising multifunctional prohealing drug candidate for chronic nonhealing skin wounds but also highlighted the unique roles of "small" peptides in the elucidation of "big" human disease mechanisms.


Assuntos
Queimaduras , Diabetes Mellitus , Animais , Humanos , Camundongos , Queimaduras/tratamento farmacológico , Queimaduras/metabolismo , Diabetes Mellitus/metabolismo , Inflamação/metabolismo , Simulação de Acoplamento Molecular , NF-kappa B/metabolismo , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Peptídeos/química , Pele/metabolismo , Receptor 4 Toll-Like/metabolismo
2.
Analyst ; 149(4): 1074-1080, 2024 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-37955046

RESUMO

Breath analysis may provide a convenient and non-invasive method for clinical monitoring of chronic kidney disease (CKD) progression. However, few breath volatile organic compounds (VOCs) indicating progression of CKD have been reported. In this study, we used gas chromatography-mass spectrometry (GC-MS) for untargeted detection of breath VOCs in stage 1, 3, and 5 CKD patients. The results showed that, the levels of breath 4-heptanone, n-octane, and n-dodecane gradually increased from CKD stage 1 to stage 5, and their increasing rates from CKD stage 3 to stage 5 were higher than those from CKD stage 1 to stage 3. Gender, smoking habits, age, and body mass index (BMI) had insignificant impact on the levels of the three breath VOCs. The accuracies of the polynomial support vector machine (SVM) and K-nearest neighbour (KNN) models based on 4-heptanone + n-octane + n-dodecane combination in distinguishing CKD stages 1, 3, and 5 were 76.3% and 72.8%, respectively. The combination of 4-heptanone + n-octane + n-dodecane was superior to any single component for monitoring CKD progression. These discoveries have valuable implications for long-term clinical monitoring of CKD and improving our understanding of CKD.


Assuntos
Alcanos , Cetonas , Octanos , Insuficiência Renal Crônica , Compostos Orgânicos Voláteis , Humanos , Compostos Orgânicos Voláteis/análise , Insuficiência Renal Crônica/diagnóstico , Testes Respiratórios/métodos
3.
Bioengineering (Basel) ; 10(12)2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38136007

RESUMO

In response to the pressing need for robust disease diagnosis from gastrointestinal tract (GIT) endoscopic images, we proposed FLATer, a fast, lightweight, and highly accurate transformer-based model. FLATer consists of a residual block, a vision transformer module, and a spatial attention block, which concurrently focuses on local features and global attention. It can leverage the capabilities of both convolutional neural networks (CNNs) and vision transformers (ViT). We decomposed the classification of endoscopic images into two subtasks: a binary classification to discern between normal and pathological images and a further multi-class classification to categorize images into specific diseases, namely ulcerative colitis, polyps, and esophagitis. FLATer has exhibited exceptional prowess in these tasks, achieving 96.4% accuracy in binary classification and 99.7% accuracy in ternary classification, surpassing most existing models. Notably, FLATer could maintain impressive performance when trained from scratch, underscoring its robustness. In addition to the high precision, FLATer boasted remarkable efficiency, reaching a notable throughput of 16.4k images per second, which positions FLATer as a compelling candidate for rapid disease identification in clinical practice.

4.
Am J Cancer Res ; 13(10): 4579-4596, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37970359

RESUMO

Mucin-type O-glycosylation, a posttranslational modification of membrane and secretory proteins, facilitates metastasis and immune escape in tumor cells. N-acetylgalactosaminyl-transferase 5 (GALNT5), the enzyme initiating mucin-type O-glycosylation, is known to advance the progression of various tumors. Yet, the comprehensive role of GALNT5 in pan-cancer scenarios remains to be elucidated. In this research, we conducted a database-centric pan-cancer expression analysis of GALNT5. We examined its aberrant expression, assessed its prognostic implications, and explored the correlations between GALNT5 expression and factors such as ferroptosis, immune cell infiltration levels, and immune checkpoint gene expression across multiple tumor types. To substantiate GALNT5's role, we analyzed cell proliferation, migration, invasion, and ferroptosis in PAAD cells after GALNT5 knockdown. Additionally, RNA-seq was employed to discern potential downstream pathways influenced by GALNT5. Our findings indicate that GALNT5 expression is heightened in the majority of tumors, correlating with the prognosis of multiple cancers. There's a notable association between GALNT5 levels and ferroptosis-related genes, immune cell infiltration, and immune checkpoint genes. In PAAD specifically, the role of GALNT5 was further probed. Knockdown of GALNT5 curtailed the proliferation, migration, and invasion capacities of PAAD cells, concurrently promoting ferroptosis. Moreover, in vivo studies demonstrated that GALNT5 inhibition stunted PAAD tumor growth. The RNA-seq analysis unveiled inflammation and immune-centric pathways, such as the TNF signaling pathway, as potential downstream conduits of GALNT5. In conclusion, our pan-cancer study underscores GALNT5 as a potential therapeutic target for enhancing PAAD prognosis, given its strong ties with ferroptosis and immune cell infiltration. Our experiments further define GALNT5 as a novel suppressor of ferroptosis.

5.
Antiviral Res ; 216: 105659, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37369283

RESUMO

BACKGROUND: COVID-19 causes significant mortality during the recent pandemic. Data regarding the effectiveness of Paxlovid on COVID-19 patients with chronic kidney disease (CKD, eGFR <90 ml/min) are limited. METHODS: A retrospective cohort study was performed on the clinical data of the hospitalized adult patients with confirmed COVID-19 infection collected at Renji Hospital from April 7, 2022 to June 21, 2022. The association of Paxlovid treatment with early (within 5 days post diagnosis) or late (5 days or later post diagnosis) initiation time with clinical outcomes was assessed by Cox proportional hazards regression model with time-dependent covariates. RESULT: 1279 of 2387 enrollees were included in the study. Patients with early initiation of Paxlovid had a lower all-cause death rate compared to those with late initiation or without Paxlovid treatment (P = 0.046). For the CKD patients with Charlson comorbidity index (CCI) > 7, the early initiation of Paxlovid was associated with a lower all-cause death rate compared to the later initiation or the lack of Paxlovid treatment (P = 0.041). Cox regression analyses revealed that eGFR (HR 4.21 [95%, CI 1.62-10.99]), Paxlovid treatment (0.32 [0.13-0.77]), CCI (4.32 [1.64-11.40]), ICU admission (2.65 [1.09-6.49]), hsCRP (3.88 [1.46-7.80]), chronic liver disease (4.02 [1.09-14.85]) were the independent risk factors for all-cause death for CKD patients after adjusting for demographics and biochemical indexes. CONCLUSIONS: All-cause death, invasive ventilation, and ICU admission were all significantly lowered by an early initiation of Paxlovid treatment in COVID-19 patients with severe CKD.


Assuntos
COVID-19 , Insuficiência Renal Crônica , Adulto , Humanos , COVID-19/complicações , Estudos Retrospectivos , Insuficiência Renal Crônica/complicações , Fatores de Risco
6.
Front Pharmacol ; 14: 1147980, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37033654

RESUMO

Background: Nirmatrelvir/ritonavir has demonstrated effectiveness in high-risk patients with coronavirus disease 2019 (COVID-19). However, investigations on the efficacy and safety of nirmatrelvir/ritonavir in patients with kidney dysfunction are limited. Methods: Data were collected from the patients admitted to a COVID-19 referral center in Shanghai, China. Patients were at least 18 years of age and had a baseline estimated glomerular filtration rate (eGFR) of <60 ml/min/1·73 m2. The primary endpoint was a composite of all-cause mortality, intensive care unit admission, or cardiovascular events. The secondary endpoint was viral shedding. Results: Among the 195 participants, 73 received nirmatrelvir/ritonavir. A lower risk of the primary endpoint was observed in nirmatrelvir/ritonavir recipients compared with non-recipients [adjusted HR 0.56 (95% CI: 0.32-0.96); p = 0.035]. Nirmatrelvir/ritonavir recipients experienced a shorter duration of viral shedding [adjusted HR 3·70 (95%CI: 2.60-5.28); p < 0.001) and faster viral load clearance versus non-recipients. Among the nirmatrelvir/ritonavir users, earlier initiation of nirmatrelvir/ritonavir within 5 days since COVID-19 diagnosis was related with shorter viral shedding time (adjusted HR 7.84 [95% CI: 3.28-18.76]; p < 0.001) compared to late initiation. No patients reported serious adverse events during treatment. Conclusion: Our findings support the early initiation of nirmatrelvir/ritonavir for high-risk patients with impaired kidney function. This could improve patient outcomes and shorten the viral shedding period.

7.
Clin Immunol ; 248: 109271, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36806705

RESUMO

BACKGROUND: Little is known about the characteristics of lymphocyte subsets and the association with patient outcomes in COVID-19 with and without impaired kidney function. METHODS: Lymphocyte subsets were compared in COVID-19 patients with or without kidney dysfunction. The primary outcome was a composite of all-cause mortality or intensive care unit admission. Secondary outcomes included duration of viral shedding, length of hospital stay, and acute kidney injury. RESULTS: Lymphocyte subset cell counts demonstrated the lowest in patients with severe/critical COVID-19 and kidney dysfunction. Among all lymphocyte subset parameters, Th cell count was the most significant indicator for outcomes. ROC of the combined model of Th cell count and eGFR presented better predictive value than that of the other parameters. Th cell count <394.5 cells/µl and eGFR <87.5 ml/min/1·73m2 were independently associated with poor outcomes. The propensity score matching analysis revealed consistent results. CONCLUSIONS: Reduced Th cell count and eGFR may be applied as promising predictive indicators for identifying COVID-19 patients with high risk and poor outcomes.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Subpopulações de Linfócitos , Contagem de Linfócitos , Rim , Estudos Retrospectivos
8.
Radiol Case Rep ; 18(1): 397-401, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36425393

RESUMO

Ovarian granulosa cell tumor (OGCT) is a relatively rare ovarian tumor originating from ovarian sex cord-stromal cells. It is generally believed that the tumor is mainly a solid mass in the early stage, and with the volume increasing, the tumor would undergo multiple cystic changes. But few such cases have been reported. This article reports a case of transition of ovarian granulosa cell tumor from a solid mass to a cystic mass in 2 months on MR imaging in an adult woman. In this case, a 55-year-old postmenopausal woman underwent MR imaging for irregular vaginal bleeding in March 2022, during which a 6-cm cystic-solid mass was detected in the right ovary with iso-hypo intensity on T1WI, iso-hyper intensity on T2WI, and hyper intensity on DWI. After injection of the contrast medium, the mass displayed progressive and obvious enhancement, which was diagnosed as OGCT. Due to the COVID-19 pandemic, the patient was unable to receive surgery in time. Two months later, the patient returned to the hospital and underwent MRI again, when a 20-cm cyst mass was detected in the pelvis, which contained little solid component at the edge. The patient was admitted and underwent a total abdominal hysterectomy with bilateral salpingo-oophorectomy. The postoperative pathology confirmed the diagnosis of adult type stage IC1 OGCT. This finding may be precious in that it could help understand the initiation and progression of OGCT.

9.
Microsyst Nanoeng ; 8: 78, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35818382

RESUMO

The accurate, continuous analysis of healthcare-relevant gases such as nitrogen oxides (NOx) in a humid environment remains elusive for low-cost, stretchable gas sensing devices. This study presents the design and demonstration of a moisture-resistant, stretchable NOx gas sensor based on laser-induced graphene (LIG). Sandwiched between a soft elastomeric substrate and a moisture-resistant semipermeable encapsulant, the LIG sensing and electrode layer is first optimized by tuning laser processing parameters such as power, image density, and defocus distance. The gas sensor, using a needlelike LIG prepared with optimal laser processing parameters, exhibits a large response of 4.18‰ ppm-1 to NO and 6.66‰ ppm-1 to NO2, an ultralow detection limit of 8.3 ppb to NO and 4.0 ppb to NO2, fast response/recovery, and excellent selectivity. The design of a stretchable serpentine structure in the LIG electrode and strain isolation from the stiff island allows the gas sensor to be stretched by 30%. Combined with a moisture-resistant property against a relative humidity of 90%, the reported gas sensor has further been demonstrated to monitor the personal local environment during different times of the day and analyze human breath samples to classify patients with respiratory diseases from healthy volunteers. Moisture-resistant, stretchable NOx gas sensors can expand the capability of wearable devices to detect biomarkers from humans and exposed environments for early disease diagnostics.

10.
Environ Sci Pollut Res Int ; 29(47): 71696-71708, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35604610

RESUMO

To clarify the chemical characteristics, source contributions, and health risks of pollution events associated with high PM2.5 in typical industrial areas of North China, manual sampling and analysis of PM2.5 were conducted in the spring, summer, autumn, and winter of 2019 in Pingyin County, Jinan City, Shandong Province. The results showed that the total concentration of 29 components in PM2.5 was 53.4 ± 43.9 µg·m-3, including OC/EC, water-soluble ions, inorganic elements, and metal elements. The largest contribution was from the NO3- ion, at 14.6 ± 14.2 µg·m-3, followed by organic carbon (OC), SO42-, and NH4+, with concentrations of 9.3 ± 5.5, 9.1 ± 6.4, and 8.1 ± 6.8 µg·m-3, respectively. The concentrations of OC, NO3-, and SO42- were highest in winter and lowest in summer, whereas the NH4+ concentration was highest in winter and lowest in spring. Typical heavy metals had higher concentrations in autumn and winter, and lower concentrations in spring and summer. The annual average sulfur oxidation rate (SOR) and nitrogen oxidation rate (NOR) were 0.30 ± 0.14 and 0.21 ± 0.12, respectively, with the highest SO2 emission and conversion rates in winter, resulting in the SO42- concentration being highest in winter. The average concentration of secondary organic carbon in 2019 was 2.8 ± 1.9 µg·m-3, and it comprised approximately 30% of total OC. The concentrations of 18 elements including Na, Mg, and Al were between 2.3 ± 1.6 and 888.1 ± 415.2 ng·m-3, with Ni having the lowest concentration and K the highest. The health risk assessment for typical heavy metals showed that Pb poses a potential carcinogenic risk for adults, whereas As may pose a carcinogenic risk for adults, children, and adolescents. The non-carcinogenic risk coefficients for all heavy metals were lower than 1.0, indicating that the non-carcinogenic risk was negligible. Positive matrix factorization analysis indicated that coal-burning emissions contributed the largest fraction of PM2.5, accounting for 35.9% of the total. The contribution of automotive emissions is similar to that of coal, at 32.1%. The third-largest contributor was industrial sources, which accounted for 17.2%. The contributions of dust and other emissions sources to PM2.5 were 8.4% and 6.4%, respectively. This study provides reference data for policymakers to improve the air quality in the NCP.


Assuntos
Poluentes Atmosféricos , Metais Pesados , Adolescente , Aerossóis/análise , Poluentes Atmosféricos/análise , Carbono/análise , Criança , Carvão Mineral/análise , Poeira/análise , Monitoramento Ambiental/métodos , Humanos , Íons/análise , Chumbo/análise , Metais Pesados/análise , Nitrogênio/análise , Material Particulado/análise , Medição de Risco , Estações do Ano , Enxofre/análise , Emissões de Veículos/análise , Água/análise
11.
ACS Appl Mater Interfaces ; 14(15): 17818-17825, 2022 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-35394746

RESUMO

The surge in air pollution and respiratory diseases across the globe has spurred significant interest in the development of flexible gas sensors prepared by low-cost and scalable fabrication methods. However, the limited breathability in the commonly used substrate materials reduces the exchange of air and moisture to result in irritation and a low level of comfort. This study presents the design and demonstration of a breathable, flexible, and highly sensitive NO2 gas sensor based on the silver (Ag)-decorated laser-induced graphene (LIG) foam. The scalable laser direct writing transforms the self-assembled block copolymer and resin mixture with different mass ratios into highly porous LIG with varying pore sizes. Decoration of Ag nanoparticles on the porous LIG further increases the specific surface area and conductivity to result in a highly sensitive and selective composite to detect nitrogen oxides. The as-fabricated Ag/LIG gas sensor on a flexible polyethylene substrate exhibits a large response of -12‰, a fast response/recovery of 40/291 s, and a low detection limit of a few parts per billion at room temperature. Integrating the Ag/LIG composite on diverse fabric substrates further results in breathable gas sensors and intelligent clothing, which allows permeation of air and moisture to provide long-term practical use with an improved level of comfort.

12.
Front Physiol ; 11: 73, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32116781

RESUMO

Puerarin, an active compound of radix puerariae, is a major compound used in Chinese herbal medicines to treat patients with diabetic nephropathy (DN). In the previous studies, we showed that puerarin exerts renoprotective effects in Streptozocin (STZ)-induced diabetic mice through activation of Sirt1 and anti-oxidative effects. Here, we further investigated the underlying mechanism mediating the renal protective effects of puerarin in DN. We studied the effects and mechanism of puerarin in STZ-induced diabetic mice and in cultured immortalized mouse podocytes treated with high glucose. We confirmed that puerarin ameliorated urinary albumin creatinine ratio and kidney injury in STZ-induced DN mice. We found that expression of heme oxygenase 1 (HMOX-1) and Sirt1 was suppressed in diabetic glomeruli but restored by puerarin treatment at both mRNA and protein levels. Additionally, we found that puerarin induced autophagy in the kidney of DN mice. In conditionally immortalized mouse podocytes, puerarin inhibited HG-induced apoptosis and restored the mRNA and protein levels of HMOX-1 and Sirt1. Interestingly, we showed that puerarin decreased liver kinase B1 (LKB1) acetylation, thereby promoting adenosine 5'-monophosphate-activated protein kinase-dependent autophagy. Knockdown of HMOX-1 and Sirt1 expression or treatment with the autophagy inhibitor 3-methyladenine abolished the protective effects of puerarin in HG-treated podocytes. Taken together, these results suggest that puerarin protects podocytes from diabetes-induced injury through HMOX1 and Sirt1-mediated upregulation of autophagy, a novel mechanism explaining its renal protective effects in DN.

13.
J Comput Assist Tomogr ; 42(5): 714-720, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30015796

RESUMO

OBJECTIVE: This study aimed to evaluate the prediction roles of clinical plus imaging features and multidetector computed tomography (MDCT) texture analysis in preoperative risk grade classification of small bowel (SB) gastrointestinal stromal tumors (GISTs). METHODS: This study included 213 SB GIST patients. Clinical features and MDCT imaging findings were reviewed. Tumor risk stratifications were determined according to modified National Institutes of Health criteria. Random forest models were performed to evaluate the correlation of risk stratification. RESULTS: The model of clinical plus imaging findings showed an area under receiver operating characteristic curve (AUC) of 92.0%. The AUC of texture analysis based on MDCT portal phase was 93.3%, without statistical difference from that of clinical plus imaging model (P = 0.378). The AUC of the model combined clinical plus imaging features and MDCT texture analysis was 94.3%, which was significantly higher than the AUC of clinical imaging model (P = 0.042). CONCLUSION: Texture analysis may become an important comprehensive tool for preoperative risk stratification of SB GISTs.


Assuntos
Tumores do Estroma Gastrointestinal/diagnóstico por imagem , Tumores do Estroma Gastrointestinal/patologia , Processamento de Imagem Assistida por Computador/métodos , Intestino Delgado/diagnóstico por imagem , Tomografia Computadorizada Multidetectores/métodos , Cuidados Pré-Operatórios/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Intestino Delgado/patologia , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Reprodutibilidade dos Testes , Estudos Retrospectivos , Medição de Risco , Adulto Jovem
14.
BMC Nephrol ; 19(1): 46, 2018 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-29486724

RESUMO

BACKGROUND: Significant attention has been directed toward the high incidence of malignant tumours that occur post-transplantation. However, there are few reports of myeloid sarcomas (MSs) following renal transplantation. CASE PRESENTATION: This case report describes a 26-year-old male patient who presented with repeatedly high creatinine levels and hydronephrosis six months post-renal transplantation. Surgical pathology revealed ureteral MS; however, the tumour recurred following resection. Bone marrow biopsy indicated that the patient also had acute promyelocytic leukaemia. The tumour was treated with local radiotherapy, and the leukaemia was treated with systemic chemotherapy. The patient's conditions were satisfactory at the one-year follow-up. CONCLUSIONS: This report is the first to describe a ureteral MS post-renal transplantation. Our findings suggest that surgical resection combined with radiotherapy and chemotherapy can help control the status of patients with this condition.


Assuntos
Hidronefrose/diagnóstico por imagem , Transplante de Rim/tendências , Recidiva Local de Neoplasia/diagnóstico por imagem , Sarcoma Mieloide/diagnóstico por imagem , Neoplasias Ureterais/diagnóstico por imagem , Adulto , Seguimentos , Humanos , Hidronefrose/complicações , Hidronefrose/terapia , Transplante de Rim/efeitos adversos , Masculino , Recidiva Local de Neoplasia/complicações , Recidiva Local de Neoplasia/terapia , Sarcoma Mieloide/complicações , Sarcoma Mieloide/terapia , Neoplasias Ureterais/complicações , Neoplasias Ureterais/terapia
15.
Biochem Biophys Res Commun ; 495(2): 1908-1914, 2018 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-29242154

RESUMO

Diffuse panbronchiolitis critical region 1 (DPCR1) is located in the major histocompatibility complex (MHC) class I. It was reported to be downregulated in invasive pituitary adenoma compared with that in non-invasive tumors, but upregulated in the precursor of gastric carcinogenesis. However, the direct effect of DPCR1 on cancer cells has rarely been reported, and the role DPCR1 in pancreatic ductal adenocarcinoma (PDAC) remains unclear. The clinical sample validation and public data analysis of the present study demonstrated that DPCR1 was upregulated markedly in PDAC and this high expression was negatively correlated with the patient prognosis. Functionally, knocking down DPCR1 in PDAC cell lines inhibited cell proliferation, migration and invasion in vitro. Tumor xenograft experiments further showed that suppression of DPCR1 inhibited tumor growth in vivo. In addition, the results of RNA deep sequencing and qRT-PCR assay showed that DPCR1 participated in PADC progression by regulating nuclear factor-kappa B signaling pathway, suggesting that it might be a novel oncogene in tumor progression and a potential therapeutic target in PDAC as well.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Proteínas/metabolismo , Adulto , Animais , Carcinoma Ductal Pancreático/mortalidade , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , China/epidemiologia , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Endogâmicos C57BL , Mucinas , Invasividade Neoplásica , Neoplasias Pancreáticas/mortalidade , Prevalência , Medição de Risco , Taxa de Sobrevida , Regulação para Cima
16.
Biomark Med ; 10(7): 689-99, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27347702

RESUMO

AIM: To explore the relationship between circulating sclerostin levels and pulse wave velocity (PWV) in prevalent hemodialysis (HD) patients. PATIENTS & METHODS: 154 HD patients were enrolled and examined for serum sclerostin level, carotid-femoral pulse wave velocity (cf-PWV), abdominal artery calcification and calcaneus bone marrow density. RESULTS: Serum sclerostin level was significantly elevated in patients with arterial stiffness. Univariate correlation showed serum sclerostin level significantly correlated with intact parathyroid hormone level, cf-PWV and calcaneus bone marrow density. Multiple linear regression analysis in patients with parathyroid hormone ≤300 pg/ml showed that pulse pressure, logAACs and serum sclerostin level were significant independent factors for cf-PWV. CONCLUSION: Serum sclerostin level was significantly associated with PWV in prevalent HD patients without hyperparathyroidism.


Assuntos
Artérias/fisiologia , Proteínas Morfogenéticas Ósseas/sangue , Falência Renal Crônica/diagnóstico , Proteínas Adaptadoras de Transdução de Sinal , Idoso , Biomarcadores/sangue , Medula Óssea/patologia , Feminino , Marcadores Genéticos , Humanos , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/patologia , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Hormônio Paratireóideo/sangue , Prevalência , Análise de Onda de Pulso , Diálise Renal
17.
Neurol Sci ; 36(12): 2253-61, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26216494

RESUMO

Although intracranial ependymoma is relatively rare, it is often associated with great clinical aggressiveness and poor overall survival. There are controversies over factors affecting the prognosis of the disease. The aim of this retrospective study was to evaluate factors that may affect the therapeutic outcome and prognosis of intracranial ependymoma by reviewing the medical records of 49 patients who were surgically treated in our hospital between 2001 and 2014. Univariate and multivariate analyses were performed to identify prognostic variables relative to patient and tumor characteristics, and treatment modalities. All 49 patients (24 men and 25 women; mean age 27.6 years) underwent surgical resection, of whom 14 patients also underwent postoperative radiotherapy. Local recurrence was found in 15 (48.8 %) patients, and 22 (51.2 %) patients died during the follow-up periods. The 5-year recurrence rate was 65 % and the survival rate was 51 %. The results of statistical analysis suggested that preoperative extraventricular drainage and surgical resection extent were prognostic factors related to progression-free survival, and that age, surgical resection extent and histological grade were closely associated with survival. Interestingly, there was a significant correlation between the symptom of hydrocephalus and age (P = 0.010), and patients with a better clinical status (KPS ≥ 80) were significantly associated with a lower WHO grade (P = 0.007). In conclusion, we confirmed that surgical resection extent was the major independent factor affecting both recurrence and survival of patients with intracranial ependymoma, while age and WHO grade were prognostic factors affecting survival but not recurrence.


Assuntos
Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Ependimoma/diagnóstico , Ependimoma/terapia , Recidiva Local de Neoplasia/diagnóstico , Adolescente , Adulto , Neoplasias Encefálicas/mortalidade , Criança , Pré-Escolar , Terapia Combinada , Intervalo Livre de Doença , Ependimoma/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/terapia , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do Tratamento , Adulto Jovem
18.
Ann Clin Lab Sci ; 45(1): 17-22, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25696005

RESUMO

OBJECTIVE: To investigate the relationship of fibroblast growth factor-23 (FGF23) to coronary calcification and prognosis in patients with chronic kidney disease (CKD) stages 3-5D. METHOD: We determined serum levels of intact FGF23 in 150 patients with CKD stages 3-5D, using an enzyme-linked immunosorbent assay (ELISA). The coronary calcification was detected with multi-slice CT, and its relationship to FGF23 was analyzed. These patients were followed up over a period of 35±3 months. RESULT: Serum FGF23 levels of patients with CKD stages 3-5D were significantly higher than those of the healthy control group (p<0.01). There was a significant positive correlation between serum FGF23 levels and coronary calcification score (CaS) (r=0.177, p<0.05). Age, dialysis vintage, and FGF23 levels were independent risk factors for coronary calcification in patients with CKD stages 3-5D. Receiver-operating characteristic (ROC) curves showed that the sensitivity and specificity of FGF23 were 62.5% and 75.9%, respectively, for diagnosing coronary calcification, with an area of 0.705 under the curve (p<0.01). Kaplan-Meier analysis revealed that survival rates were significantly better in patients with lower FGF23 levels (p<0.05). In Cox regression analysis, FGF23 levels and severe coronary calcification (CaS>400) were independent risk factors for all-cause mortality. CONCLUSION: Serum FGF23 level in patients with CKD stages 3-5D was significantly higher than in the healthy controls. These increased FGF23 levels are likely associated with coronary calcification and poor prognosis.


Assuntos
Calcinose/sangue , Fatores de Crescimento de Fibroblastos/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/patologia , Calcinose/complicações , Cardiomiopatias , Feminino , Fator de Crescimento de Fibroblastos 23 , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Insuficiência Renal Crônica/complicações
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