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1.
Comput Struct Biotechnol J ; 21: 5476-5490, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38022698

RESUMO

Precise diagnosis of early prostate cancer (PCa) is critical for preventing tumor progression. However, the diagnostic outcomes of currently used markers are far from satisfactory due to the low sensitivity or specificity. Here, we identified a diagnostic subpopulation in PCa tissue with the integrating analysis of single-cell and bulk RNA-seq. The representative markers of this subpopulation were extracted to perform intersection analysis with early-PCa-related gene module generated from weighted correlation network analysis (WGCNA). A total of 24 overlapping genes were obtained, the diagnostic roles of which were validated by distinguishing normal and tumorous prostate samples from the public dataset. A least absolute shrinkage and selection operator (LASSO) model was constructed based on these genes and the obtained 24-gene panel showed high sensitivity and specificity for PCa diagnosis, with better identifying capability of PCa than the commercially used gene panel of Oncotype DX. The top two risk factors, TRPM4 and PODXL2, were verified to be highly expressed in early PCa tissues by multiplex immunostaining, and PODXL2 was more sensitive and specific compared to TRPM4 and the pathologically used marker AMACR for early PCa diagnosis, suggesting a novel and promising pathology marker.

2.
Front Biosci (Landmark Ed) ; 28(8): 177, 2023 08 23.
Artigo em Inglês | MEDLINE | ID: mdl-37664918

RESUMO

BACKGROUND: Propionibacterium acnes causes upregulation of inflammatory factors, such as cycloxygenase-2, prostaglandin E2, interleukin-1ß, and tumor necrosis factor-alpha, increased levels of reactive oxygen species (ROS) and inward flow of calcium ions. This causes increased levels of the antimicrobial peptide LL-37 and inflammation of the skin, leading to redness, swelling, itching and other symptoms. Schisandra chinensis fruit oil (SCO) is rich in lignan active ingredients with various antioxidant and anti-inflammatory properties. METHODS: In this study, SCO is obtained by supercritical CO2 fluid extraction. SCO's anti-inflammatory actions were investigated using P. acnes-induced inflammation HaCaT cells model. A method based on reversed-phase high-pressure liquid chromatography with a diode array detector was developed and validated for the simultaneous detection of five lignan components. Levels of inflammatory factors and LL-37 were measured by ELISA kit and western blot respectively. Ca2+ and ROS levels detected by flow cytometry. RESULTS: The experimental results show that the contents of schisanol A, schisanol B, schisanin A, schisanin B, and schisanin C were 33.89 ± 0.24, 14.89 ± 0.45, 8.92 ± 0.02, 29.14 ± 0.67, and 4.74 ± 0.09 mg/g, respectively. Studies have demonstrated that SCO can alleviate skin inflammation by inhibiting the COX-2/PGE2 and NF-κB signalling pathway. In addition, SCO can inhibit ROS production, significantly block inward Ca2+ flow, alleviate cell damage, and modulate the content of the antimicrobial peptide LL-37. CONCLUSIONS: In summary, our study elucidated the anti-inflammatory activity of SCO in a cell model and provided a scientific basis for its application as a raw material in skin care.


Assuntos
Propionibacterium acnes , Schisandra , Humanos , Cálcio , Catelicidinas , Frutas , Células HaCaT , Espécies Reativas de Oxigênio , Inflamação/tratamento farmacológico , Peptídeos Antimicrobianos , Dinoprostona
3.
Cells ; 12(12)2023 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-37371120

RESUMO

Kaposi's sarcoma-associated herpesvirus (KSHV) and the Epstein-Barr virus (EBV) are double-stranded DNA oncogenic gammaherpesviruses. These two viruses are associated with multiple human malignancies, including both B and T cell lymphomas, as well as epithelial- and endothelial-derived cancers. KSHV and EBV establish a life-long latent infection in the human host with intermittent periods of lytic replication. Infection with these viruses induce the expression of both viral and host RNA transcripts and activates several RNA sensors including RIG-I-like receptors (RLRs), Toll-like receptors (TLRs), protein kinase R (PKR) and adenosine deaminases acting on RNA (ADAR1). Activation of these RNA sensors induces the innate immune response to antagonize the virus. To counteract this, KSHV and EBV utilize both viral and cellular proteins to block the innate immune pathways and facilitate their own infection. In this review, we summarize how gammaherpesviral infections activate RNA sensors and induce their downstream signaling cascade, as well as how these viruses evade the antiviral signaling pathways to successfully establish latent infection and undergo lytic reactivation.


Assuntos
Infecções por Vírus Epstein-Barr , Herpesvirus Humano 8 , Infecção Latente , Humanos , RNA , Herpesvirus Humano 4/fisiologia , Imunidade Inata
4.
PLoS Pathog ; 18(11): e1010990, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36417478

RESUMO

Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr (EBV) are gammaherpesviruses associated with multiple human malignancies. KSHV is the etiological agent of Kaposi's Sarcoma, primary effusion lymphoma (PEL) and multicentric Castleman's disease (MCD). EBV is associated with Burkitt's lymphoma (BL), Hodgkin's lymphoma (HL), nasopharyngeal carcinoma (NPC) and gastric carcinoma (GC). KSHV and EBV establish life-long latency in the human host with intermittent periods of lytic reactivation. Here, we identified a cellular factor named transforming growth factor-beta regulator 4 (TBRG4) that plays a role in the gammaherpesvirus lifecycle. We find that TBRG4, a protein that is localized to the mitochondria, can regulate lytic reactivation from latency of both KSHV and EBV. Knockdown of TBRG4 in cells latently infected with KSHV or EBV induced viral lytic gene transcription and replication. TBRG4 deficiency causes mitochondrial stress and increases reactive oxygen species (ROS) production. Treatment with a ROS scavenger decreased viral reactivation from latency in TBRG4-depleted cells. These data suggest that TBRG4 serves as a cellular repressor of KSHV and EBV reactivation through the regulation of ROS production.


Assuntos
Herpesvirus Humano 4 , Herpesvirus Humano 8 , Proteínas Mitocondriais , Latência Viral , Humanos , Herpesvirus Humano 4/fisiologia , Herpesvirus Humano 8/fisiologia , Proteínas Mitocondriais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Ligação a RNA/metabolismo
5.
Front Immunol ; 13: 851312, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35619698

RESUMO

Background: Almost 40% of patients with kidney renal clear cell carcinoma (KIRC) with advanced cancers eventually develop to metastases, and their 5-year survival rates are approximately 10%. Aberrant DNA methylations are significantly associated with the development of KIRC. The aim of our present study was to identify suitable ferroptosis- and immune-related (FI) biomarkers correlated with aberrant methylations to improve the prognosis and diagnosis of KIRC. Methods: ChAMP and DESeq2 in R (3.6.2) were used to screen the differentially expressed methylation probes and differentially expressed genes, respectively. Univariate and multivariate Cox regression were used to identify the overall survival (OS)-related biomarkers. Results: We finally identified five FI biomarkers (CCR4, CMTM3, IFITM1, MX2, and NR3C2) that were independently correlated with the OS of KIRC. The area under the curve value of the receiver operating characteristic value of prognosis model was 0.74, 0.68, and 0.72 in the training, validation, and entire cohorts, respectively. The sensitivity and specificity of the diagnosis model were 0.8698 and 0.9722, respectively. In addition, the prognosis model was also significantly correlated with several immune cells and factors. Conclusion: Our present study suggested that these five FI-DEGs (CCR4, CMTM3, IFITM1, MX2, and NR3C2) could be used as prognosis and diagnosis biomarkers for patients with KIRC, but further cross-validation clinical studies are still needed to confirm them.


Assuntos
Carcinoma de Células Renais , Ferroptose , Neoplasias Renais , Biomarcadores Tumorais/genética , Carcinoma de Células Renais/diagnóstico , Carcinoma de Células Renais/genética , Ferroptose/genética , Humanos , Rim/patologia , Neoplasias Renais/diagnóstico , Neoplasias Renais/genética , Neoplasias Renais/patologia , Prognóstico
6.
Diagn Pathol ; 17(1): 13, 2022 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-35057825

RESUMO

BACKGROUND: STAT3 plays an important role in cervical cancer. LC3B, the most potential molecular biomarker of autophagy that may promote or inhibit cancer progression, can be downregulated by STAT3. However the role of STAT3 in the autophagy of cervical cancer remains unclear. PURPOSE: This study aimed to evaluate the relationship between STAT3 and LC3B in protein level, and verify whether STAT3 promotes proliferation, migration and plate colony formation by inhibiting autophagy of cervical cancer cells through bcl2-beclin1 axis. RESULTS: STAT3 was overexpressed in cervical cancer tissues, and negatively correlated with the expression level of LC3B. STAT3 knockout or knockdown significantly increased the autophagy level and decreased proliferation, migration, plate colony formation and subcutaneous tumorigenesis of cervical cancer cells in vitro and in vivo. STAT3 is known to mediate autophagy through Bcl2-Beclin1 complex. Bcl2 was positively whereas Beclin1 negatively correlated with STAT3 expression, indicating that Bcl2-Beclin1 complex involved in this transition. CONCLUSION: STAT3 may upregulate the autophagy level of cervical cancer cells through the Bcl2-Beclin1 axis. This indicates that STAT3 may be an important prognostic and therapeutic target for cervical cancer.


Assuntos
Neoplasias do Colo do Útero , Autofagia , Proteína Beclina-1/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Fator de Transcrição STAT3/metabolismo , Neoplasias do Colo do Útero/genética
7.
Front Nutr ; 9: 1043879, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36712545

RESUMO

Introduction: Sea buckthorn (Hippophae rhamnoides) seed oil is rich in unsaturated fatty acids, and is thus susceptible to oxidation and rancidity. Microencapsulation technology allows the effective protection of active substances, thereby prolonging the deterioration time and shelf life. Methods: In this study, H. rhamnoides microcapsules were prepared using a spray-drying method, and the microencapsulation parameters were optimized. The morphological characteristics, structural parameters, and stability of the microcapsules were determined using scanning electron microscopy, Fourier transform infrared spectroscopy, thermogravimetric analysis, differential scanning calorimetry, and oil oxidation stability testing. Results: Based on encapsulation efficiency (EE, %) and the particle size (D50) of the microcapsules, the optimal preparation conditions were characterized as a wall material consisting of soy protein isolate and soybean polysaccharide (2:3), a wall concentration of 15%, a core-to-wall ratio of 1:3, and an inlet temperature of 160°C. Under these optimal conditions, the encapsulation efficiency was 95.30 ± 2.67%, with a yield of 57.03 ± 3.71% and a particle size of 7.96 ± 1.04 µm. Discussion: Furthermore, the effectiveness of microencapsulation in protecting the biological activity of H. rhamnoides seed oil was confirmed by an antioxidation test. Thus, the results of this study showcase the successful microencapsulation of H. rhamnoides seed oil, thereby significantly improving its stability.

8.
Mol Biol Rep ; 48(12): 8033-8044, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34743271

RESUMO

BACKGROUND: The imbalance of vasoconstrictor and vasodilator axes of the renin-angiotensin system (RAS) is observed in hypertension. Exercise regulates RAS level and improves vascular function. This study focused on the contribution of RAS axes in vascular function of mesenteric arteries and exercise-induced DNA methylation of the Agtr1a (AT1aR) and Mas1 (MasR) genes in hypertension. METHODS: Spontaneously hypertensive rats (SHRs) and Wistar-Kyoto rats were randomized into exercise or sedentary group. Levels of plasma RAS components, vascular tone, and DNA methylation markers were measured. RESULTS: Blood pressure of SHR was markedly reduced after 12 weeks of aerobic exercise. RAS peptides in plasma were all increased with an imbalanced upregulation of Ang II and Ang-(1-7) in SHR, exercise revised the level of RAS and increased Ang-(1-7)/Ang II. The vasoconstriction response induced by Ang II was mainly via type 1 receptors (AT1R), while this contraction was inhibited by Mas receptor (MasR). mRNA and protein of AT1R and MasR were both upregulated in SHR, whereas exercise significantly suppressed this imbalanced increase and increased MasR/AT1R ratio. Exercise hypermethylated Agtr1a and Mas1 genes, associating with increased DNMT1 and DNMT3b and SAM/SAH. CONCLUSIONS: Aerobic exercise ameliorates vascular function via hypermethylation of the Agtr1a and Mas1 genes and restores the vasoconstrictor and vasodilator axes balance.


Assuntos
Proto-Oncogene Mas/metabolismo , Hipertensão Arterial Pulmonar/terapia , Receptor Tipo 1 de Angiotensina/metabolismo , Angiotensina II/metabolismo , Animais , Artérias/metabolismo , Pressão Sanguínea/efeitos dos fármacos , DNA/metabolismo , Metilação de DNA/genética , Epigênese Genética/genética , Hipertensão/metabolismo , Masculino , Artérias Mesentéricas/fisiologia , Óxido Nítrico/metabolismo , Condicionamento Físico Animal/métodos , Esforço Físico/genética , Esforço Físico/fisiologia , Hipertensão Arterial Pulmonar/fisiopatologia , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Receptor Tipo 1 de Angiotensina/fisiologia , Sistema Renina-Angiotensina/fisiologia , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologia
9.
BMC Fam Pract ; 22(1): 23, 2021 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-33453725

RESUMO

BACKGROUND: Domestic migration poses a challenge for China as migrants have little access to preventive healthcare services and are vulnerable to certain risks and diseases. This research sought to unveil and explore the determinant factors associated with health education utilization as a key aspect in basic public health services for migrants in Beijing, China. METHODS: A sample of 863 inter-provincial migrants, 18 years old and above, was selected by three-stage stratified cluster sampling method in urban-rural fringe areas of Beijing during 2016 to 2017. Face-to-face structured interviews were conducted in the questionnaire survey. The effects of the explanatory variables on health education utilization from predisposing, enabling, health behaviors and need variables were used to demonstrate by Anderson health service utilization model. RESULTS: The study revealed that 61.6% migrants desired to receive health education, while only 53.8% of them received in the past year. There were differences in the utilization and needs of health education among the migrants in different ages and genders. Many migrants desired to gain access to various types of health education information from the internet. Chi-square independence test lists such major determinant factors in migrants whole health education as age, "Hukou" registration system, marital status, education level, long-term residence plan in Beijing, one or more children in Beijing, employment status, housing source, average daily working time, exercises, health knowledge, smoking, self-rated health. The binary logistic regression indicates that the migrants with younger age, high education level, one or more children in Beijing, exercises and good self-rated health were more likely to receive whole health education. The results also show that average daily working time of enabling variables and exercise of health behavior variables were the strong and consistent determinants of three types of health education utilization, including communicable, non-communicable and occupational diseases. CONCLUSION: Gaps exist between the needs and utilization in health education and more attention should be given to the migrants with heavy workload and low education level. Feasible policies and measures, such as multiple health information channels, should be vigorously implemented to ensure equitable and easy access to health education for migrants.


Assuntos
Migrantes , Pequim , China , Estudos Transversais , Utilização de Instalações e Serviços , Feminino , Educação em Saúde , Humanos , Masculino , População Rural
10.
J Cell Mol Med ; 24(11): 6362-6372, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32319715

RESUMO

Glioblastoma (GBM) belongs to the high-grade (IV) gliomas with extremely poor prognosis. Accumulating evidence uncovered the key roles of long non-coding RNAs (lncRNAs) in GBM development. This study aimed to determine the biological actions and the clinical relevance of lncRNA MIR4435-2 Host Gene (MIR4435-2HG) in GBM. Data from GEPIA database showed that MIR4435-2HG was up-regulated in GBM tissues and high expression of MIR4435-2HG correlated with shorter overall survival of GBM patients. Further experimental assays verified the up-regulation of MIR4435-2HG in GBM tissues and cell lines. In vitro cell studies and in vivo animal studies showed that knockdown of MIR4435-2HG resulted in the inhibition of GBM cell proliferation and invasion and in vivo tumour growth, while MIR4435-2HG overexpression driven GBM progression. Furthermore, MIR44435-2HG was found to sponge miR-1224-5p and suppress miR-1224-5p expression; overexpression of miR-1224-5p attenuated the enhancement in GBM cell proliferation and invasion induced by MIR4435-2HG overexpression. In a subsequent study, miR-1224-5p was found to target transforming growth factor-beta receptor type 2 (TGFBR2) and repressed TGFBR2 expression, and in vitro assays showed that miR-1224-5p exerted tumour-suppressive effects via targeting TGFBR2. More importantly, TGFRB2 knockdown antagonized hyper-proliferation and invasion of GBM cells with MIR4435-2HG overexpression. Clinically, the down-regulation of miR-1224-5p and up-regulation of TGFBR2 were verified in the GBM clinical samples. Taken together, the present study suggests the oncogenic role of MIR4435-2HG in GBM and underlies the key function of MIR4435-2HG-driven GBM progression via targeting miR-1224-5p/TGFBR2 axis.


Assuntos
Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioblastoma/genética , Glioblastoma/patologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Receptor do Fator de Crescimento Transformador beta Tipo II/metabolismo , Transdução de Sinais , Animais , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Masculino , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Invasividade Neoplásica , RNA Longo não Codificante/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/genética , Regulação para Cima/genética
11.
Cell Rep ; 31(4): 107564, 2020 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-32348766

RESUMO

Kaposi's sarcoma-associated herpesvirus (KSHV) is a double-stranded DNA virus that exhibits two alternative life cycles: latency and lytic reactivation. During lytic reactivation, host innate immune responses are activated to restrict viral replication. Here, we report that adenosine deaminase acting on RNA 1 (ADAR1) is required for optimal KSHV lytic reactivation from latency. Knockdown of ADAR1 in KSHV latently infected cells inhibits viral gene transcription and viral replication during KSHV lytic reactivation. ADAR1 deficiency also significantly increases type I interferon production during KSHV reactivation. This increased interferon response is dependent on activation of the RIG-I-like receptor (RLR) pathway. Depletion of ADAR1 together with either RIG-I, MDA5, or MAVS reverses the increased IFNß production and rescues KSHV lytic replication. These data suggest that ADAR1 serves as a proviral factor for KSHV lytic reactivation and facilitates DNA virus reactivation by dampening the RLR pathway-mediated innate immune response.


Assuntos
Adenosina Desaminase/metabolismo , Proteína DEAD-box 58/metabolismo , Herpesvirus Humano 8/fisiologia , Proteínas de Ligação a RNA/metabolismo , Receptores Imunológicos/metabolismo , Técnicas de Inativação de Genes , Células HEK293 , Herpesvirus Humano 8/metabolismo , Humanos , Interferon beta/biossíntese , Transdução de Sinais , Ativação Viral , Latência Viral
12.
Environ Int ; 139: 105672, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32248022

RESUMO

There are currently increasingly concerns over DNA damage related to free radicals due to their vital roles in human health, especially high-performance detection method. Herein, we report an ultra- sensitive monitoring of DNA damage associated with free radicals exposure using interdigitated electrode (IDE) array for the first time. The proposed IDE array was equipped with DNA-wrapped carbon nanotube-based bridges, which utilized the DNA damage mechanism due to the free radicals' attack and the efficient electrical detection nature of the interdigitated electrode. Experiments have been performed, and the results showed the device's capability for detecting DNA damage induced by multiple free radicals generated from different sources, including the Fenton reaction, UV radiation and cigarette smoke, showing the promising ability for DNA damage detection. In addition, the carbon nanotubes bridge-based interdigitated electrode sensor enabled different levels of sensing of DNA damage with great sensitivity and a wide detection range. It was illustrated that the ultrasensitive detection of free radicals generated from ultraviolet radiation (15 min - 125 min), cigarette smoke tar (1 µg/mL to 10 µg/mL) and Fenton reaction under different concentration of H2O2 (2.5 pM - 100 pM), have been detected successfully. Typically, the IDE array supports further performance improvement for the electrochemical detection in an ultrasensitive and high throughput route.


Assuntos
Técnicas Biossensoriais , Nanotubos de Carbono , Dano ao DNA , Eletrodos , Humanos , Peróxido de Hidrogênio , Nanotubos de Carbono/toxicidade , Raios Ultravioleta
13.
Environ Pollut ; 259: 113841, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31883477

RESUMO

Nicotine (Nic) exposed to the environment which comes from tobacco products is the main addictive agent and specific classes of hazardous compound that merit concern. In this study, we have established a fast and reliable method to achieve specific detection of Nic in natural nicotiana tabacum within 30 s through a miniaturized platform based on screen printed gold electrode (SPE). A simple electrochemical pretreatment mean was employed on gold surface that led to the exposure of Au (111) facet and a convenient sample pretreatment method was adopted to realize the extraction of Nic in tobacco. The present electrochemical sensor exhibits an ample range of sensing from 10 µg/g to 200 µg/g, which is able to compliance with tobacco industry testing standards of actual samples. Over 60 sampling points from different origins in China or other countries were performed with direct analysis using this method and satisfactory results have been obtained. The proposed approach was demonstrated to be a very promising platform for significantly improving analytical efficiency in laboratories as well as for monitoring the source reduction control of Nic in the environment.


Assuntos
Técnicas de Química Analítica/métodos , Nicotiana , Nicotina , China , Eletrodos , Nicotina/análise , Nicotiana/química
14.
J Hazard Mater ; 389: 121834, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-31843407

RESUMO

Environmental problems caused by the large-scale use of chemical pesticides are becoming more and more serious, and the removal of chemical pesticides from the ecological environment by microbial degradation has attracted wide attention. In this study, using enrichment screening with seven chemical pesticides as the sole carbon source, a mixed microbial culture (PCS-1) was obtained from the continuous cropping of strawberry fields. The microbial community composition, degradation ability, and detoxification effect of PCS-1 was determined for the seven pesticides. Inoculation with PCS-1 showed significant degradation of and tolerance to the seven pesticides. Microbial community composition analysis indicated that Pseudomonas, Enterobacter, Aspergillus, and Rhodotorula were the dominant genera for the degradation of the seven pesticides by PCS-1. The concentration of the seven pesticides was 10 mg L-1 in hydroponic and soil culture experiments. The fresh weight, plant height, and root length of PCS-1-inoculated alfalfa (Medicago sativa) significantly increased compared with those of non-PCS-1-inoculated M. sativa. PCS-1 not only effectively degraded the residual content of the seven pesticides in water and soil but also reduced the pesticide residues in the roots, stems, and leaves of M. sativa. This study shows that PCS-1 may be important in environmental remediation involving the seven pesticides.


Assuntos
Poluentes Ambientais/análise , Medicago sativa/efeitos dos fármacos , Microbiota/efeitos dos fármacos , Praguicidas/análise , Microbiologia do Solo , Poluentes do Solo/análise , Aspergillus/efeitos dos fármacos , Aspergillus/crescimento & desenvolvimento , Biodegradação Ambiental , Enterobacter/efeitos dos fármacos , Enterobacter/crescimento & desenvolvimento , Poluentes Ambientais/toxicidade , Medicago sativa/crescimento & desenvolvimento , Resíduos de Praguicidas/análise , Resíduos de Praguicidas/toxicidade , Praguicidas/toxicidade , Pseudomonas/efeitos dos fármacos , Pseudomonas/crescimento & desenvolvimento , Rhodotorula/efeitos dos fármacos , Rhodotorula/crescimento & desenvolvimento , Poluentes do Solo/toxicidade
15.
J Cancer ; 10(24): 6095-6104, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31762819

RESUMO

BACKGROUND: Circulating tumor cell (CTC)-based patient-derived cells are ideal models for investigating the molecular basis of cancer. However, the rarity and heterogeneity of CTCs as well as the difficulties of primary culture limit their practical application. Establishing efficient in vitro culture methods and functionally characterizing CTCs is essential for cancer studies. To this end, we developed an experimental protocol for the isolation, expansion, and identification of breast cancer CTCs. METHODS: The CTC-3 cell line was established from peripheral blood cells of a breast cancer patient. A karyotype analysis was performed. The molecular profile was assessed by flow cytometry, quantitative real-time PCR, and western blot. The characteristics of tumors formed by CTC-3 cells were evaluated by cell growth and tumor sphere formation assays and in a mouse xenograft model. The tumors were analyzed by immunohistochemistry, immunofluorescence analysis, and hematoxylin and eosin staining. RESULTS: The CTC-3 cell line showed more aggressive growth both in vitro and in vivo than the widely used MCF-7 breast cancer cell line. CTC-3 cells were also more resistant to chemotherapeutic agents, and gene profiling indicated higher expression levels of the epithelial-to-mesenchymal transition and stemness markers as compared to MCF-7 cells. CONCLUSIONS: CTC-3 cells are a better model for investigating the malignant behavior of breast cancer than existing cell lines.

16.
Nutr Metab (Lond) ; 16: 37, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31160916

RESUMO

BACKGROUND: Proliferative diabetic retinopathy (PDR), a sight-threatening retinopathy, is the leading cause of irreversible blindness in adults. Despite strict control of systemic risk factors, a fraction of patients with diabetes develop PDR, suggesting the existence of other potential pathogenic factors underlying PDR. This study aimed to investigate the plasma metabotype of patients with PDR and to identify novel metabolite markers for PDR. Biomarkers identified from this study will provide scientific insight and new strategies for the early diagnosis and intervention of diabetic retinopathy. METHODS: A total of 1024 patients with type 2 diabetes were screened. To match clinical parameters between case and control subjects, patients with PDR (PDR, n = 21) or those with a duration of diabetes of ≥10 years but without diabetic retinopathy (NDR, n = 21) were assigned to the present case-control study. Distinct metabolite profiles of serum were examined using liquid chromatography-mass spectrometry (LC-MS). RESULTS: The distinct metabolites between PDR and NDR groups were significantly enriched in 9 KEGG pathways (P < 0.05, impact > 0.1), namely, alanine, aspartate and glutamate metabolism, caffeine metabolism, beta-alanine metabolism, purine metabolism, cysteine and methionine metabolism, sulfur metabolism, sphingosine metabolism, and arginine and proline metabolism. A total of 63 altered metabolites played important roles in these pathways. Finally, 4 metabolites were selected as candidate biomarkers for PDR, namely, fumaric acid, uridine, acetic acid, and cytidine. The area under the curve for these biomarkers were 0.96, 0.95, 1.0, and 0.95, respectively. CONCLUSIONS: This study suggested that impairment in the metabolism of pyrimidines, arginine and proline were identified as metabolic dysregulation associated with PDR. And fumaric acid, uridine, acetic acid, and cytidine might be potential biomarkers for PDR. Fumaric acid was firstly reported as a novel metabolite marker with no prior reports of association with diabetes or diabetic retinopathy, which might provide insights into potential new pathogenic pathways for diabetic retinopathy.

17.
Eur J Pharmacol ; 842: 177-188, 2019 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-30391348

RESUMO

The pineal hormone melatonin is a neuroendocrine hormone with high membrane permeability that is involved in regulation of circadian rhythm of several biological functions. Large-conductance Ca2+-activated K+ (BKCa) channels are abundantly expressed in vascular smooth muscle cells and play an important role in vascular tone regulation. We investigated the mechanisms through which myocyte BKCa channels mediate effects of melatonin on cerebral arteries (CAs). Arterial contractility measurements showed that melatonin alone did not change vascular tone in CAs; however, it induced concentration-dependent vasodilation of phenylephrine-induced contraction in CAs. In the presence of the potent endothelial oxide synthase inhibitor, Nω-nitro-L-arginine methyl ester, melatonin-elicited relaxation was significantly inhibited by iberiotoxin (BKCa channel blocker). Melatonin significantly increased BKCa currents but not voltage-gated K+ (KV) currents in whole-cell recordings. Melatonin decreased the amplitude of Ca2+ sparks and spontaneous transient outward currents (STOCs), however, a significant increase in open probability of BKCa channels was observed in both inside-out and cell-attached patch-clamp recordings. This melatonin-induced enhancement of BKCa channel activity was significantly suppressed by luzindole (melatonin MT1/MT2 receptor inhibitor), U73122 (phospholipase C (PLC) inhibitor), and Ro31-8220 (protein kinase C (PKC) inhibitor). Melatonin had no significant effects on sarcoplasmic reticulum release of Ca2+. These findings indicate that melatonin-induced vasorelaxation of CAs is partially attributable to direct (passing through the cell membrane) and indirect (via melatonin MT1/MT2 receptors-PLC-PKC pathway) activation of BKCa channels on CA myocytes.


Assuntos
Artérias Cerebrais/efeitos dos fármacos , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Melatonina/farmacologia , Miócitos de Músculo Liso/efeitos dos fármacos , Proteína Quinase C/metabolismo , Receptor MT1 de Melatonina/metabolismo , Receptor MT2 de Melatonina/metabolismo , Animais , Pressão Sanguínea/efeitos dos fármacos , Artérias Cerebrais/citologia , Artérias Cerebrais/fisiologia , Relação Dose-Resposta a Droga , Fenômenos Eletrofisiológicos/efeitos dos fármacos , Masculino , Miócitos de Músculo Liso/metabolismo , Peptídeos/farmacologia , Ratos , Ratos Wistar
18.
Zhongguo Dang Dai Er Ke Za Zhi ; 18(1): 24-8, 2016 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-26781408

RESUMO

OBJECTIVE: To investigate the values of urinary netrin-1 and kidney injury molecule-1 (KIM-1) in the early diagnosis of acute kidney injury (AKI) induced by neonatal asphyxia. METHODS: A total of 80 full-term neonates with asphyxia were enrolled (mild asphyxia: 34 neonates; severe asphyxia: 46 neonates). Forty normal full-term neonates were selected as the control group. Urinary samples were collected from the neonates in the three groups within 12 hours and 13-48 hours after birth. ELISA was applied to measure urinary levels of netrin-1 and KIM-1. Peripheral venous blood samples were also collected to measure serum creatinine (Scr) level. RESULTS: Compared with the control group, the asphyxia group had significantly higher urinary levels of netrin-1 and KIM-1 within 48 hours after birth and a significantly higher Scr level within 13-48 hours after birth (P<0.05). The neonates in the AKI group had significantly higher urinary levels of netrin-1 and KIM-1 and Scr level within 48 hours after birth than those in the non-AKI group (P<0.05). The areas under the receiver operating characteristic curve for urinary netrin-1 and KIM-1 levels within 12 hours after birth to predict AKI after asphyxia were 0.878 (95% CI: 0.775-0.981; P<0.01) and 0.899 (95% CI: 0.829-0.969; P<0.01), respectively. Any two indicators of urinary netrin-1 level, urinary KIM-1 level, and Scr level within 12 hours after neonatal asphyxia had a positive correlation (P<0.05). CONCLUSIONS: Urinary netrin-1 and KIM-1 levels increase significantly when neonates with asphyxia develop AKI. Urinary netrin-1 and KIM-1 can be used as indicators for the early diagnosis of AKI after asphyxia.


Assuntos
Injúria Renal Aguda/diagnóstico , Asfixia Neonatal/complicações , Glicoproteínas de Membrana/urina , Fatores de Crescimento Neural/urina , Proteínas Supressoras de Tumor/urina , Injúria Renal Aguda/urina , Feminino , Receptor Celular 1 do Vírus da Hepatite A , Humanos , Recém-Nascido , Masculino , Netrina-1 , Receptores Virais
19.
Zhonghua Yan Ke Za Zhi ; 45(4): 301-8, 2009 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-19575960

RESUMO

OBJECTIVE: To study the clinical characteristics of choroidal metastasis (CM) to promote the early diagnosis and differentiate from other choroidal tumors. METHODS: Retrospective clinical observational cases. All patients with choroidal metastasis underwent ophthalmologic examination including best corrected visual acuity (VA), slit-lamp examination, binocular indirect funduscopy, color photography, fundus fluorescein angiography (FFA), indocyanine-green angiography (ICGA), optical coherence tomography (OCT), A and B scan ultrasound examination, magnetic resonance image (MRI) as well as CT of the thorax, etc. RESULTS: Nine eyes of 5 patients with CM were examined. Unilateral choroidal involvement was present in 1 patient, bilateral in 4 cases. There were 1 case male and 4 case females. The age of these patients ranged from 31 to 56 years, median 45 years. Ocular symptoms included reduced vision in 4 patients and visual distortion in 1 patient. Visual acuity was 20/400- < 20/63 in four eyes; 20/63- < 20/30 in two eyes and >or= 20/30 in three eyes. The primary cancer site was in the lung in 3 patients, in the breast in 1 patient and in the stomach in 1 patient. Fundus characteristics: Typical CM was more often in the plateau-shaped than in the dome-shaped; yellow-white or mottled in color and associated with subretinal fluid and retinal detachment. The tumor was found in the macular area and juxtapapillary area in 6 eyes, in the area between the macula and the equator in 3 eyes. CM was solitary in 5 eyes and showed multiple lesions in 4 eyes. By FA the lesions showed mottled hyperfluorescence in early stage and leakage in late stage. By ICGA the lesion showed blocked fluorescence and hypofluorescence. Choroidal mass showed moderate irregular internal reflectivity in A-scan ultrasound. B-scan showed a plateau-shaped solid mass. MRI examination of the lesion revealed moderate short T1W and T2W signals. The cancer antigen increased to 16.28 and 4.95 microg/L in two cases. CA125 increased to 160.5 kU/L in one case. CONCLUSIONS: The choroid is the most common site for metastases. CM may precede the diagnosis of primary tumor. Evaluation of A, B scan ultrasound, CT of thorax and cancer antigen test may be important to exclude primary carcinoma from lung and breast in patients with yellow-white in color, plateau-shaped choroidal lesions, especially in both eyes, and without known metastatic diseases.


Assuntos
Carcinoma/diagnóstico , Carcinoma/secundário , Neoplasias da Coroide/diagnóstico , Neoplasias da Coroide/secundário , Adulto , Diagnóstico Precoce , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Estudos Retrospectivos
20.
Zhonghua Yan Ke Za Zhi ; 42(4): 296-8, 2006 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-16762203

RESUMO

Based on the manuscripts received by several ophthalmologic journals, major issues regarding current ophthalmic research aspects in China were analyzed and discussed, including the selection of project, the design of research, the choice of statistical treatments and the techniques of writing research manuscripts. This article provides suggestions for Chinese ophthalmologists to improve the quality of their research work.


Assuntos
Oftalmologia , Projetos de Pesquisa , Dissertações Acadêmicas como Assunto , China , Estatística como Assunto
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