RESUMO
Acute lymphoblastic leukemia (ALL) is a heterogeneous clonal disease originated from B- or T-cell lymphoid precursor cells. ALL is often refractory or relapses after treatment. Novel treatments are anxiously needed in order to achieve a better response and prolonged overall survival in ALL patients. In the present study, we aimed at examining the anti-tumor effect of niclosamide on ALL. We investigated the effects of niclosamide on the proliferation and apoptosis in vitro, the growth of ALL cells in xenografted NCG mice. The results showed that niclosamide treatment potently inhibited the growth of ALL cells and induced apoptosis via elevating the levels of reactive oxygen species (ROS) and activating TP53. These findings suggest that niclosamide may be a promisingly potential agent for ALL therapy.
RESUMO
Metastasis remains the principal cause of cancer-related lethality despite advancements in cancer treatment. Dysfunctional epigenetic alterations are crucial in the metastatic cascade. Among these, super-enhancers (SEs), emerging as new epigenetic regulators, consist of large clusters of regulatory elements that drive the high-level expression of genes essential for the oncogenic process, upon which cancer cells develop a profound dependency. These SE-driven oncogenes play an important role in regulating various facets of metastasis, including the promotion of tumor proliferation in primary and distal metastatic organs, facilitating cellular migration and invasion into the vasculature, triggering epithelial-mesenchymal transition, enhancing cancer stem cell-like properties, circumventing immune detection, and adapting to the heterogeneity of metastatic niches. This heavy reliance on SE-mediated transcription delineates a vulnerable target for therapeutic intervention in cancer cells. In this article, we review current insights into the characteristics, identification methodologies, formation, and activation mechanisms of SEs. We also elaborate the oncogenic roles and regulatory functions of SEs in the context of cancer metastasis. Ultimately, we discuss the potential of SEs as novel therapeutic targets and their implications in clinical oncology, offering insights into future directions for innovative cancer treatment strategies.
Assuntos
Elementos Facilitadores Genéticos , Regulação Neoplásica da Expressão Gênica , Metástase Neoplásica , Neoplasias , Humanos , Neoplasias/patologia , Neoplasias/genética , Neoplasias/metabolismo , Neoplasias/terapia , Animais , Epigênese Genética , Terapia de Alvo Molecular , Transição Epitelial-MesenquimalRESUMO
OBJECTIVES: The current work aimed to provide a comprehensive single-cell landscape of lupus nephritis (LN) kidneys, including immune and non-immune cells, identify disease-associated cell populations and unravel their participation within the kidney microenvironment. METHODS: Single-cell RNA and T cell receptor sequencing were performed on renal biopsy tissues from 40 patients with LN and 6 healthy donors as controls. Matched peripheral blood samples from seven LN patients were also sequenced. Multiplex immunohistochemical analysis was performed on an independent cohort of 60 patients and validated using flow cytometric characterisation of human kidney tissues and in vitro assays. RESULTS: We uncovered a notable enrichment of CD163+ dendritic cells (DC3s) in LN kidneys, which exhibited a positive correlation with the severity of LN. In contrast to their counterparts in blood, DC3s in LN kidney displayed activated and highly proinflammatory phenotype. DC3s showed strong interactions with CD4+ T cells, contributing to intrarenal T cell clonal expansion, activation of CD4+ effector T cell and polarisation towards Th1/Th17. Injured proximal tubular epithelial cells (iPTECs) may orchestrate DC3 activation, adhesion and recruitment within the LN kidneys. In cultures, blood DC3s treated with iPTECs acquired distinct capabilities to polarise Th1/Th17 cells. Remarkably, the enumeration of kidney DC3s might be a potential biomarker for induction treatment response in LN patients. CONCLUSION: The intricate interplay involving DC3s, T cells and tubular epithelial cells within kidneys may substantially contribute to LN pathogenesis. The enumeration of renal DC3 holds potential as a valuable stratification feature for guiding LN patient treatment decisions in clinical practice.
Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Humanos , Biomarcadores/metabolismo , Células Dendríticas/metabolismo , Rim/patologia , Lúpus Eritematoso Sistêmico/patologia , Nefrite Lúpica/patologia , Células Th1 , Antígenos de Diferenciação Mielomonocítica , Antígenos CDRESUMO
OBJECTIVE: The aim of this study was to investigate serum levels of soluble B-cell maturation antigen (sBCMA) in childhood-onset systemic lupus erythematous (cSLE) patients with renal involvement, and to elucidate their association with clinical characteristics. METHODS: 116 cases of cSLE patients with renal involvement (84 females and 32 males; median age 11.6 (10.1, 12.9) years) hospitalized in Department of Pediatric Nephrology and Rheumatology, the First Affiliated Hospital, Sun Yat-sen University and 31 healthy controls (HCs) were enrolled. Serum concentrations of sBCMA were determined using enzyme-linked immunosorbent assay (ELISA). Clinical and laboratory information of cSLE patients were retrospectively analyzed. RESULTS: Serum sBCMA levels were significantly increased in primary cSLE when compared with treated cSLE patients and HCs, whereas there was no significant difference between treated cSLE patients and HCs. Patients with high disease activity displayed higher serum sBCMA levels compared with those with no or mild to moderate disease activity. Positive correlation was observed between serum sBCMA levels and systemic lupus erythematosus disease activity index-2K (SLEDAI-2K), antinuclear antibody titers, anti-double-stranded DNA titers, erythrocyte sedimentation rate, and immunoglobulin G levels, while sBCMA levels were negatively correlated with blood white blood cell count, hemoglobin, platelet count, complement C3 and C4 levels. Serum sBCMA levels decreased as disease ameliorated after treatments among 11 cases with follow-up examinations. CONCLUSIONS: In cSLE patients with renal involvement, serum sBCMA levels correlated significantly with disease activity, immunological, and hematological parameters, but not with renal parameters. Our results suggest the potential and significance of serum sBCMA as a biomarker in cSLE patients.
Assuntos
Antígeno de Maturação de Linfócitos B , Nefropatias , Lúpus Eritematoso Sistêmico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Humanos , Masculino , Feminino , Criança , Antígeno de Maturação de Linfócitos B/sangue , Nefropatias/etiologia , BiomarcadoresRESUMO
BACKGROUND: Positive antineutrophil cytoplasmic antibody (ANCA) serology in adult-onset lupus nephritis (LN) is associated with more active disease and distinct renal pathology, but data with respect to childhood-onset LN remain scarce. Here, we aimed to determine the impact of positive ANCA serology on clinical and histopathologic features and renal outcomes in children with LN from multiple centers. METHODS: Clinical and histopathologic data of 61 ANCA-positive and 330 ANCA-negative LN children (1Assuntos
Lúpus Eritematoso Sistêmico
, Nefrite Lúpica
, Adulto
, Criança
, Humanos
, Adolescente
, Nefrite Lúpica/patologia
, Estudos Retrospectivos
, Anticorpos Anticitoplasma de Neutrófilos
, Rim/patologia
, Hematúria
RESUMO
AIMS: To evaluate the potential applications of soy protein-glucan-catechin (SGC) complexes prepared with different ultrasound times in stabilising high internal phase Pickering emulsion (HIPPE) and delivering curcumin. METHODS: The SGC complexes were characterised by particle size, morphology, zeta potential, Fourier transform infra-red, and fluorescence spectroscopy. Formation and stability of curcumin emulsions were monitored by droplet size, microstructure, rheological property, lipid oxidation, and in vitro digestion. RESULTS: Short-time ultrasound-induced complexes (SGC-U15) exhibited a small size and wettability of â¼82.5°. The chemical stability and bioaccessibility of curcumin was greatly improved by SGC-U15-stabilised HIPPEs, even after 70 days of storage, heating at 100 °C for 30 min, ultraviolet irradiation for 120 min, and in vitro digestion, owing to the formation of elastic gel-like structure at the oil/water interfaces. CONCLUSION: Our findings may contribute to the design of emulsion-based delivery systems using ultrasound-induced protein-polysaccharide-polyphenol complexes.
Assuntos
Catequina , Curcumina , Nanopartículas , beta-Glucanas , Emulsões , Proteínas de SojaRESUMO
Metastasis, a main cause of death in tumor patients, is a complicated process that involves multiple steps, presenting a major clinical challenge. Tumor cells break the physical boundaries of a primary tumor, intravasate into the lumina of blood vessels, travel around through blood circulation, extravasate into distant organs, colonize the host organs, and eventually develop into the foci of metastatic cancer. The metastasis of tumor cells exhibits organ-tropism, i.e., tumor cells preferentially spread to specific organs. Liver is a common site for metastasis. The pattern of metastasis in uveal melanoma, colorectal carcinoma, and pancreatic ductal adenocarcinoma shows organ-tropism for liver. The anatomical structure of liver determines its hemodynamic characteristics, e.g., low pressure and slow blood flow, which tend to facilitate the stasis and colonization of tumor cells in the liver. Besides the hemodynamic features, the metastatic colonization of liver depends largely on the interaction between tumor cells and the hepatic microenvironment (especially liver-resident cellular components). Resident cells of the hepatic microenvironment include hepatocytes, liver sinusoidal endothelial cells (LSECs), hepatic stellate cells (HSCs), Kupffer cells (KCs), etc. Herein, we discussed the role and significance of liver-resident cells in the metastatic colonization of tumor in the liver.
Assuntos
Células Endoteliais , Neoplasias Hepáticas , Humanos , Fígado/patologia , Hepatócitos , Células de Kupffer/patologia , Células Estreladas do Fígado/patologia , Neoplasias Hepáticas/patologia , Microambiente Tumoral/fisiologiaRESUMO
BACKGROUND: Our previous study discovers that Jun N-terminal kinase pathway-associated phosphatase (JKAP) is dysregulated and negatively links with the disease severity in acute ischemic stroke (AIS) patients. This study intended to further evaluate the linkage of JKAP and interleukin (IL)-17A with anxiety, depression, and cognitive impairment in AIS patients. METHODS: Serum JKAP and IL-17A levels in 120 AIS patients at admission, 1st (D1), 3rd (D3), 7th (D7) day after admission, and from 20 controls, were detected by ELISA. Hospital Anxiety and Depression Scale (HADS) and Mini-Mental State Examination (MMSE) were assessed in AIS patients at discharge. RESULTS: JKAP (p < 0.001) was reduced, but IL-17A (p < 0.001) was increased in AIS patients versus controls, and negatively correlated with each other in AIS patients (p = 0.014). In AIS patients, JKAP was reduced from baseline to D1 and then increased to D7 (p < 0.001), while IL-17A exhibited an opposite trend (p < 0.001). Notably, JKAP at D3 was negatively linked with HADS-anxiety score (p = 0.044), then decreased JKAP at D3 (p = 0.017) and D7 (p = 0.037) related to increased anxiety occurrence. However, JKAP was not linked to HADS-depression score or depression occurrence. Besides, JKAP at multiple time points were positively associated with MMSE score (all p < 0.05); decreased JKAP at D3 (p = 0.017) and D7 (p = 0.026) related to raised cognitive impairment occurrence. CONCLUSION: JKAP initially decreases then shows an increasing trend after disease onset, and its decrement relates to elevated IL-17A, anxiety and cognitive impairment in AIS patients.
Assuntos
Disfunção Cognitiva , Depressão , AVC Isquêmico , Humanos , Ansiedade/metabolismo , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/metabolismo , Depressão/metabolismo , Fosfatases de Especificidade Dupla/metabolismo , Interleucina-17/metabolismo , AVC Isquêmico/complicações , Acidente Vascular Cerebral/complicaçõesRESUMO
OBJECTIVE: JKAP modifies T-cell immune response and inflammation, also involves in cardia-cerebrovascular disease etiology. This study intended to explore JKAP's relation with T-helper 1 (Th1), T-helper 17 (Th17) cell levels, clinical properties, and recurrence-free survival (RFS) in acute ischemic stroke (AIS) patients. METHODS: A total of 155 AIS patients were analyzed. Serum JKAP, interferon-gamma (IFN-γ), and interleukin-17A (IL-17A) were detected by ELISA; then blood Th1 and Th17 cells were quantified by flow cytometry. Besides, 30 healthy subjects were enrolled as controls to detect JKAP, Th1, and Th17 cells. RESULTS: JKAP level was lower (p < 0.001), Th1 cells were not differed (p = 0.068), but Th17 cells were elevated in AIS patients versus controls (p < 0.001). Meanwhile, JKAP was negatively correlated with Th1 cells (p = 0.038), Th17 cells (P<0.001), IFN-γ (p = 0.002), and IL-17A (p < 0.001) in AIS patients. JKAP was negatively associated with the National Institutes of Health Stroke Scale (NIHSS) score (p < 0.001), but Th17 cells (p = 0.001), IFN-γ (p = 0.035), and IL-17A (p = 0.008) levels were positively associated with NIHSS score. Additionally, accumulating RFS was numerically longer in patients with JKAP Quantile (Q) 4 than patients with JKAP Q1-Q3 (p = 0.068), and numerically better in patients with JKAP Q3-Q4 than patients with JKAP Q1-Q2 (p = 0.069), but without statistical significance. CONCLUSION: JKAP correlates with lower Th1 and Th17 cell percentages as well as milder disease severity.
Assuntos
Interleucina-17 , AVC Isquêmico , Humanos , Interferon gama , Sistema de Sinalização das MAP Quinases , Monoéster Fosfórico Hidrolases , Células Th1 , Células Th17RESUMO
PURPOSE: Oral squamous cell carcinoma (OSCC) local recurrence and distant metastasis remain a poorly understood clinical challenge. The objective of this study was to investigate how dysregulation of miR-382-5p impacts invasion and dissemination of OSCC. METHODS: Tissue samples were collected from 20 subjects with OSCC. Expression levels of miR-382-5p were determined by quantitative real-time polymerase chain reaction (qRT-PCR), and correlations with clinical characteristics were investigated. qRT-PCR was used to determine the miR-382-5p and peptidyl-prolyl cis/trans isomerase (PTEN) expression in tumor tissues, adjacent normal tissues, normal human oral keratinocyte line, and OSCC line (SCC-9). Cell proliferation, invasion, and migration of knock-in and knock-down miR-382-5p transfectants were assessed using cell counting kit-8 and Transwell assays. PTEN was confirmed to be a downstream target using a TargetScan prediction, dual-luciferase reporter assays, and western blot analysis. Statistical analysis of experimental data was performed with SPSS 22.0 software. RESULTS: We found high expression of miR-382-5p and significant downregulation of PTEN in tumor tissues and SCC-9 cells from OSCC patients (P < .05). miR-382-5p expression was lower in early stage (I + II) than in late stage (III + IV), while PTEN exhibited higher expression in early stage (I + II) instead of in late stage (III + IV) (P < .05). In addition, overexpression of miR-382-5p promoted the proliferation, invasion, and migration of OSCC cells. However, the proliferation, invasion, and migration of OSCC cells were inhibited after suppression of miR-382-5p. Finally, PTEN is downregulated by miR-382-5p. CONCLUSION: MiR-382-5p supports proliferation, invasion, and migration of OSCC cells through the PTEN pathway. Further investigation may improve our understanding of OSCC local recurrence and distant metastasis.
Assuntos
MicroRNAs , Neoplasias Bucais , PTEN Fosfo-Hidrolase , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
This study aimed to explore the association between LIM domain kinase 1 (LIMK1) expression in prostate cancer (PCa) tissues with advanced pathological features, lymph node metastases and biochemical recurrence. A total of 279 PCa specimens from patients who underwent radical prostatectomy and 50 benign prostatic hyperplasia (BPH) specimens were collected to construct tissue microarray, which were subjected to immunohistochemical staining for LIMK1 expression subsequently. Logistic and Cox regression analysis were used to evaluate the relationship between LIMK1 expression and clinicopathological features of patients with PCa. Immunohistochemical staining assay demonstrated that LIMK1 expression was significantly higher in PCa than BPH specimens (77.1% vs 26.0%; P < .001). LIMK1 expression was significantly higher in positive lymph node specimens than corresponding PCa specimens (P = .002; P < .001). Up-regulation of LIMK1 was associated with prostate volume, prostate-specific antigen, prostate-specific antigen density, Gleason score, T stage, lymph node metastases, extracapsular extension and seminal vesicle invasion, and positive surgical margin. Multivariate logistic regression analysis demonstrated that LIMK1 was an independent risk factor for PCa lymph node metastasis (P < .05). Multivariate Cox regression analysis revealed that the up-regulation of LIMK1 was an independent risk factor for biochemical recurrence. Kaplan-Meier analysis indicated that up-regulation LIMK1 was associated with shortened biochemical-free survival (BFS) after radical prostatectomy (P < .001). In conclusion, LIMK1 was significantly up-regulated in PCa and positive lymph node specimens and correlated with lymph node metastasis and shortened BFS of PCa. The underlying molecular mechanism of LIMK1 in PCa should be further evaluated.
Assuntos
Quinases Lim/genética , Metástase Linfática/genética , Recidiva Local de Neoplasia/genética , Neoplasias da Próstata/genética , Idoso , Intervalo Livre de Doença , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Linfonodos/metabolismo , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Próstata/metabolismo , Próstata/patologia , Neoplasias da Próstata/patologia , Análise de SobrevidaRESUMO
The significance of actin-related protein 2/3 complex subunit 4 (ARPC4) expression in bladder cancer, and its potential role in the invasion and migration of bladder cancer cells, has yet to be determined. This study was to identify the correlation between ARPC4 and lymph node metastasis, and to determine the role of ARPC4 in the invasive migration of T24 bladder cancer cells. One hundred and ninety-eight bladder cancer tissues and 40 normal bladder and lymph node tissues were examined. Tissue microarrays were constructed and subjected to immunohistochemical stating for ARPC4. Multiple logistic analysis was used to determine risk factors associated with bladder cancer metastasis. ARPC4 expression in T24 bladder cancer cells was suppressed using small interfering RNA and changes in protein levels were determined by Western blot analysis. The proliferation of bladder cancer cells after knocking down of ARPC4 was determined by cell counting kit-8. The effects of ARPC4 knockdown on T24 cell invasion and migration was determined using transwell and wound healing assays. Immunofluorescence analysis was performed to examine changes in pseudopodia formation and actin cytoskeleton structure. The expression of ARPC4 was elevated in bladder cancer tissues than normal tissues (84.3% vs 27.5%, P < 0.001). The multivariate logistic analysis demonstrated that the level of ARPC4, as a risk factor, was correlated with lymphatic metastasis (P < 0.05). ARPC4 knockdown attenuated proliferation, migration, invasion, and pseudopodia formation in T24 cells. ARPC4 expression, as a risk factor, is associated with lymphatic metastasis and is upregulated in bladder cancer tissues in comparison with normal tissues. Inhibition of ARPC4 expression significantly attenuates the proliferation, migration, and invasion of bladder cancer cell, possibly due to defects in pseudopodia formation.
Assuntos
Actinas/metabolismo , Metástase Linfática , Neoplasias da Bexiga Urinária/metabolismo , Citoesqueleto de Actina/metabolismo , Adulto , Idoso , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Cistectomia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica , RNA Interferente Pequeno/metabolismo , Fatores de Risco , Análise Serial de Tecidos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgia , CicatrizaçãoRESUMO
BACKGROUND: Hepatic metastasis develops in ~ 50% of uveal melanoma (UM) patients with no effective treatments. Although GNAQ/GNA11 mutations are believed to confer pathogenesis of UM, the underlying mechanism of liver metastasis remains poorly understood. Given that profound epigenetic evolution may occur in the long journey of circulating tumor cells (CTCs) to distant organs, we hypothesized that EZH2 endowed tumor cells with enhanced malignant features (e.g., stemness and motility) during hepatic metastasis in UM. We aimed to test this hypothesis and explore whether EZH2 was a therapeutic target for hepatic metastatic UM patients. METHODS: Expression of EZH2 in UM was detected by qRT-PCR, Western blotting and immunohistochemistry staining. Proliferation, apoptosis, cancer stem-like cells (CSCs) properties, migration and invasion were evaluated under circumstances of treatment with either EZH2 shRNA or EZH2 inhibitor GSK126. Antitumor activity and frequency of CSCs were determined by xenografted and PDX models with NOD/SCID mice. Hepatic metastasis was evaluated with NOG mice. RESULTS: We found that EZH2 overexpressed in UM promoted the growth of UM; EZH2 increased the percentage and self-renewal of CSCs by miR-29c-DVL2-ß-catenin signaling; EZH2 facilitates migration and invasion of UM cells via RhoGDIγ-Rac1 axis. Targeting EZH2 either by genetics or small molecule inhibitor GSK126 decreased CSCs and motility and abrogated the liver metastasis of UM. CONCLUSIONS: These findings validate EZH2 as a druggable target in metastatic UM patients, and may shed light on the understanding and interfering the complicated metastatic process.
Assuntos
Biomarcadores Tumorais/metabolismo , Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Melanoma/patologia , Células-Tronco Neoplásicas/patologia , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/metabolismo , Neoplasias Uveais/patologia , Animais , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Humanos , Indóis/farmacologia , Melanoma/tratamento farmacológico , Melanoma/genética , Melanoma/metabolismo , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Piridonas/farmacologia , Células Tumorais Cultivadas , Proteínas Supressoras de Tumor/genética , Ubiquitina Tiolesterase/genética , Neoplasias Uveais/tratamento farmacológico , Neoplasias Uveais/genética , Neoplasias Uveais/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
BACKGROUND Evidence indicates that there is an important role for long non-coding RNAs (lncRNA) in numerous cellular processes and that lncRNAs dysregulation contributes to tumor progression. Improved insight into the molecular characteristics of bladder cancer is required to predict outcomes and to develop a new rationale for targeted therapeutic strategies. Bioinformatics methods, including functional enrichment and network analysis combined with survival analysis, are required to process a large volume of data to obtain further information about differentially expressed genes (DEGs) in bladder cancer. This study aimed to explore the role of lncRNAs and their regulation network in bladder cancer. MATERIAL AND METHODS We analyzed bladder cancer data by The Cancer Genome Atlas profiling to identify differentially expressed lncRNAs in bladder cancer. The genes involved in the circlncRNAnet database were evaluated using Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), evolutionary relationship analysis, and protein-protein interaction (PPI) networks. RESULTS Two new lncRNAs, ADAMTS9-AS1 and LINC00460, were shown to be differentially expressed in bladder cancer. Patients were divided into 2 groups (high expression and low expression) according to their median expression values. The overall survival and disease-free survival of patients with high ADAMTS9-AS1 bladder cancer were significantly shorter; the expression of LINC00460 had no significant correlation with survival. GO and KEGG analysis of the 2 lncRNA-related genes revealed that these lncRNAs played a vital role in tumorigenesis. Bioinformatics analysis showed that key genes related to LINC00460, including CXCL, CCL, and CSF2, may be related to the development of bladder cancer. The low expression of ADAMTS9-AS1 may influence the survival rate of bladder cancer with the hub gene as a target. CONCLUSIONS LncRNA, including LINC00460 and ADAMTS9-AS1, might play a crucial role in the biosynthesis network of bladder cancer. Differential expression results of ADAMTS9-AS1 suggests it may be correlated with a worse prognosis and a shorter survival time. We outlined the biosynthesis network that regulates lncRNAs in bladder cancer. Further experimental data is needed to validate our results.
Assuntos
RNA Longo não Codificante/genética , Neoplasias da Bexiga Urinária/genética , Biomarcadores Tumorais/genética , Biologia Computacional , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Prognóstico , Mapas de Interação de Proteínas , Análise de Sobrevida , Transcriptoma , Neoplasias da Bexiga Urinária/diagnósticoRESUMO
Benign prostatic hyperplasia (BPH) is one of the most common causes of lower urinary tract symptoms (LUTS) in elderly man. However, the underlying molecular mechanisms of BPH have not been completely elucidated. We identified the key genes and pathways by using analysis of Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using edgeR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for the DEGs by Database for Annotation, Visualization and Integrated Discovery (DAVID) database and ConsensusPathDB, respectively. Then, protein-protein interaction (PPI) networks were established by the Search Tool for the Retrieval of Interacting Genes (STRING) database and visualized by Cytoscape software. Finally, we identified 660 DEGs ultimately including 268 upregulated genes and 392 downregulated genes. GO analysis revealed that DEGs were mainly enriched in extracellular exosome, identical protein binding, mitochondrial adenosine triphosphate (ATP) synthesis coupled proton transport, extracelluar matrix, focal adhesion, cytosol, Golgi apparatus, cytoplasm, protein binding, and Golgi membrane. Focal adhesion pathway, FoxO signaling pathway, and autophagy pathway were selected. Ubiquitin-conjugating enzyme E2 C (UBE2C), serine/threonine kinase (AKT1), mitogen-activated protein kinase 1 (MAPK1), cyclin B1 (CCNB1), polo-like kinase 1 (PLK1) were filtrated as the hub genes according to the degree of connectivity from the PPI network. The five hub genes including UBE2C, AKT1, MAPK1, CCNB1, PLK1 may play key roles in the pathogenesis of benign prostatic hyperplasia (BPH). Focal adhesion pathway, FoxO signaling pathway, and autophagy pathway may be crucial for the progression of BPH.
Assuntos
Genes Neoplásicos , Hiperplasia Prostática/genética , Transdução de Sinais/genética , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Ontologia Genética , Genoma , Humanos , Masculino , Mapas de Interação de Proteínas/genéticaRESUMO
BACKGROUND: Asian citrus psyllid (ACP) is the primary vector responsible for the transmission of the phloem-limited bacteria Candidatus Liberibacter spp., associated with huanglongbing (HLB), which causes great loss to the citrus industry. Although the roles of leaf color and volatile compounds in the orientation of ACP have been proven, the quantification of color and allelochemicals in the host plant are kept unclear, especially in wild citrus germplasms. RESULTS: Chongyi wild mandarin significantly attracted more ACP than wild Hong Kong kumquat, 'Gannan zao' navel orange and orange jasmine did in the four-choice and olfactometer assays. The color parameters of the tender leaves from Chongyi wild mandarin and 'Gannan zao' were similar. The yellow color in both of them was less saturated than that of the other two plants species, but Chongyi wild mandarin had significant lower carotenoid content (P < 0.05). Notably metabolic profiling differences were observed among the healthy tender shoots from the four tested plants via UPLC-QQQ-MS and GC-MS analyses. Comparing with the other three plant species, 66 and 50 metabolites with significantly different contents in Chongyi wild mandarin were selected as UPLC-identified and GC-identified metabolites of interest (P < 0.05), respectively. Flavonoids accounted for a large group of secondary metabolites of interest, which may function as stimulants or repellents of ACP. Higher content of salicylic acid o-hexoside and lower content of (+)-jasmonic acid in Chongyi wild mandarin may lead to higher amount of methyl salicylate (an ACP attractant) and lower amount of trans-ocimene (an attractant to herbivores' natural enemies) as well as the suppression of JA-mediated wounding response. This kind of synergistic or antagonistic effect among the metabolites differentially accumulated in Chongyi wild mandarin made it a more attractive host plant to ACP. CONCLUSIONS: Less saturated yellow color, high amount of attractants, low amount of repellents and insensitivity of JA-mediated wounding response are the four possible reasons why Chongyi wild mandarin attracted more ACP. This work may shed light on the olfactory and visual response of ACP to wild citrus germplasm hosts, and suggest the feasibility of developing ACP attractants or repellents patterned on potential metabolites.
Assuntos
Hemípteros/fisiologia , Folhas de Planta/metabolismo , Rutaceae/metabolismo , Animais , Cromatografia Líquida de Alta Pressão , Citrus/metabolismo , Cor , Flavonoides/metabolismo , Cromatografia Gasosa-Espectrometria de Massas , Compostos Orgânicos Voláteis/metabolismoRESUMO
BACKGROUND: Data on the pharmacological management of acute agitation in schizophrenia are scarce. The aim of this study is to investigate the prescription practices in the treatment of agitation in Chinese patients with schizophrenia. METHODS: We conducted a large, multicenter, observational study in 14 psychiatry hospitals in China. Newly hospitalized schizophrenia patients with the PANSS-EC total score ≥ 14 and a value ≥4 on at least one of its five items were included in the study. Their drug treatments of the first 2 weeks in hospital were recorded by the researchers. RESULTS: Eight hundred and 53 patients enrolled in and 847 (99.30%) completed the study. All participants were prescribed antipsychotics, 40 (4.72%) were prescribed benzodiazepine in conjunction with antipsychotics and 81 were treated with modified electric convulsive therapy (MECT). Four hundred and 12 (48.64%) patients were prescribed only one antipsychotic, in the order of olanzapine (120 patients, 29.13%), followed by risperidone (101 patients, 24.51%) and clozapine (41 patients, 9.95%). About 435 (51.36%) participants received antipsychotic polypharmacy, mostly haloperidol + risperidone (23.45%), haloperidol+ olanzapine (17.01%), olanzapine+ ziprasidone (5.30%), haloperidol + clozapine (4.37%) and haloperidol + quetiapine (3.90%). Binary logistic regression analysis suggests that a high BARS score (OR 2.091, 95%CI 1.140-3.124), severe agitation (OR 1.846, 95%CL 1.266-2.693), unemployment or retirement (OR 1.614, 95%CL 1.189-2.190) and aggressiveness on baseline (OR 1.469, 95%CL 1.032-2.091) were related to an increased antipsychotic polypharmacy odds. Male sex (OR 0.592, 95%CL 0.436-0.803) and schizophrenia in older persons (age ≥ 55 years, OR 0.466, 95%CL 0.240-0.902) were less likely to be associated with antipsychotic polypharmacy. CONCLUSION: The present study demonstrates that monotherapy and polypharmacy display equally common patterns of antipsychotic usage in managing agitation associated with schizophrenia in China. The extent and behavioral activities of agitation and several other factors were associated with polypharmacy.
Assuntos
Antipsicóticos/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Esquizofrenia/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Agressão/efeitos dos fármacos , China , Quimioterapia Combinada , Feminino , Humanos , Pacientes Internados/psicologia , Pacientes Internados/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , PolimedicaçãoRESUMO
Purpose: To evaluate the feasibility of soy protein hydrolysates (SPH)-tannic acid (TA) complex nanoparticle obtained by photocatalysis (SPH-T (P)) to construct curcumin (Cur) delivery vehicles. Methods: The interaction behaviour of SPH-T (P) was investigated using Fourier transform infra-red, X-ray diffraction and differential scanning calorimeter analyzes. Formation and stability of the complexes were characterised by particle size, morphology, zeta potential, and in vitro release. Results: Negatively charged Cur-loaded complex with small size (<100 nm), spherical cluster shape and uniform size distribution were formed through the driving force of electrostatic attraction, followed by hydrogen bonding. The presence of photocatalysis in the complexes significantly improved the storage stability and in vitro sustained release of curcumin by enhancing the hydrogen bonding, hydrophobic effects and π-π stacking interactions between SPH and TA. Conclusion: SPH-T (P) would be a useful and promising delivery vehicle for encapsulating, protecting, and delivering hydrophobic nutraceuticals.
Assuntos
Antineoplásicos/administração & dosagem , Curcumina/administração & dosagem , Portadores de Fármacos/química , Proteínas de Soja/química , Taninos/química , Antineoplásicos/química , Catálise , Curcumina/química , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Hidrólise , Tamanho da PartículaRESUMO
Aim: To design novel emulsifiers with the ability to improve the storage and digestion stability of curcumin emulsions, besides to investigate the influence of phenolic acids types on the emulsify ability of soy protein-pectin-phenolic acids complexes obtained by ultrasonication. Methods: The ternary complexes were characterised by particle size, morphology, zeta potential, X-ray diffraction, Fourier transform infra-red and fluorescence spectroscopy. Additionally, changes in droplet size, charge, and microstructure were monitored as quantitative stability index of curcumin emulsions. Results: Phenolic acid types significantly affected the formation of ternary complexes. Soy protein-pectin-ferulic acid complex (S-P-F) stabilised curcumin emulsion had the best emulsifying property, followed by soy protein-pectin- ellagic acid (S-P-E), and soy protein-pectin-tannic acid complexes (S-P-T). Moreover, S-P-F emulsion was found to retain efficiently cucumin within 30 days storage (77.35%) and simulated gastrointestinal tract (64.09%). Conclusion: Protein-polysaccharide-phenolic acids emulsions are effective oral delivery systems for hydrophobic bioactives.
Assuntos
Antineoplásicos/administração & dosagem , Curcumina/administração & dosagem , Emulsões/química , Hidroxibenzoatos/química , Pectinas/química , Proteínas de Soja/química , Antineoplásicos/química , Curcumina/química , Digestão , Portadores de Fármacos/química , Estabilidade de Medicamentos , Emulsificantes/química , HumanosRESUMO
Plating battery electrodes typically deliver higher specific capacity values than insertion or conversion electrodes because the ion charge carriers represent the sole electrode active mass, and a host electrode is unnecessary. However, reversible plating electrodes are rare for electronically insulating nonmetals. Now, a highly reversible iodine plating cathode is presented that operates on the redox couples of I2 /[ZnIx (OH2 )4-x ]2-x in a water-in-salt electrolyte. The iodine plating cathode with the theoretical capacity of 211â mAh g-1 plates on carbon fiber paper as the current collector, delivering a large areal capacity of 4â mAh cm-2 . Tunable femtosecond stimulated Raman spectroscopy coupled with DFT calculations elucidate a series of [ZnIx (OH2 )4-x ]2-x superhalide ions serving as iodide vehicles in the electrolyte, which eliminates most free iodide ions, thus preventing the consequent dissolution of the cathode-plated iodine as triiodides.