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1.
Mol Cancer ; 21(1): 12, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34986849

RESUMO

BACKGROUND: More and more studies have shown that circular RNAs (circRNAs) play a critical regulatory role in many cancers. However, the potential molecular mechanism of circRNAs in prostate cancer (PCa) remains largely unknown. METHODS: Differentially expressed circRNAs were identified by RNA sequencing. The expression of hsa_circ_0003258 was evaluated using quantitative real-time PCR and RNA in situ hybridization. The impacts of hsa_circ_0003258 on the metastasis of PCa cells were investigated by a series of in vitro and in vivo assays. Lastly, the underlying mechanism of hsa_circ_0003258 was revealed by Western blot, biotin-labeled RNA pulldown, RNA immunoprecipitation, luciferase assays and rescue experiments. RESULTS: Increased expression of hsa_circ_0003258 was found in PCa tissues and was associated with advanced TNM stage and ISUP grade. Overexpression of hsa_circ_0003258 promoted PCa cell migration by inducing epithelial mesenchymal transformation (EMT) in vitro as well as tumor metastasis in vivo, while knockdown of hsa_circ_0003258 exerts the opposite effect. Mechanistically, hsa_circ_0003258 could elevate the expression of Rho GTPase activating protein 5 (ARHGAP5) via sponging miR-653-5p. In addition, hsa_circ_0003258 physically binds to insulin like growth factor 2 mRNA binding protein 3 (IGF2BP3) in the cytoplasm and enhanced HDAC4 mRNA stability, in which it activates ERK signalling pathway, then triggers EMT programming and finally accelerates the metastasis of PCa. CONCLUSIONS: Upregulation of hsa_circ_0003258 drives tumor progression through both hsa_circ_0003258/miR-653-5p/ARHGAP5 axis and hsa_circ_0003258/IGF2BP3 /HDAC4 axis. Hsa_circ_0003258 may act as a promising biomarker for metastasis of PCa and an attractive target for PCa intervention.

2.
Carcinogenesis ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35022660

RESUMO

The high incidence and vulnerability to recurrence of bladder urothelial carcinoma (BLCA) is a challenge in the clinical. Recent studies have revealed that NFE2L3 plays a vital role in the carcinogenesis and progression of different human tumors. However, the role of NFE2L3 in bladder cancer has not been elucidated. In this study, NFE2L3 expression was significantly increased in bladder cancer samples. Its high expression was associated with advanced clinicopathological characteristics and was an independent prognostic factor for overall survival (OS) and metastasis-free survival (MFS) in 106 patients with BLCA. In vitro and in vivo experiments demonstrated that NFE2L3 knockdown inhibited bladder cancer cells proliferation by inducing the cell cycle arrest and cell apoptosis. Meanwhile, NFE2L3 overexpression promotes BLCA cell migration and invasion in vitro cell lines and in vivo xenografts. Moreover, we identified many genes and pathway alterations associated with tumor progression and metastasis by performing RNA-Seq analysis and functional enrichment of NFE2L3 overexpressing BLCA cells. Mechanistic investigation reveals that overexpression of NFE2L3 promoted epithelial-mesenchymal transition (EMT) in bladder cancer cells with decreased expression of gap junction-associated protein ZO-1 and epithelial marker E-cadherin with the elevation of transcription factors Snail1 and Snail2. Finally, we performed a comprehensive proteomics analysis to explore more potential molecular mechanisms. Our findings revealed that NFE2L3 might serve as a valuable clinical prognostic biomarker and therapeutic target in BLCA.

3.
Gene ; 808: 145966, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34530089

RESUMO

This study was designed to construct a prognostic risk model to predict prognosis and immunotherapy response of bladder cancer (BCa) patinets. 350 differential expressed immune-related genes (DEIRGs) were obtained according to the transcriptome profiling and immune-related genes from the Cancer Genome Atlas (TCGA) database and ImmPort database, respectively. A prognostic risk model was constructed based on 15 hub genes through univariate, multivariate, and LASSO Cox regression analyses. The area under the receiver operating characteristic (ROC) curve was 0.743, indicating the superiority of the model. The scatter plot showed that as the risk score increased, the overall survival decreased significantly. In addition, all results were internally verified by the TCGA cohort. The model showed that the higher the grade, clinical stage, and TNM stage of BCa, the higher the risk score of patients. The tumor mutation burden of the low-risk group was generally higher than that of the high-risk group. Immune cell infiltration analysis showed that CD8 T cells, naive CD4 T cells, follicular helper T cells and M0 Macrophage were significantly different between the two groups. Several key immune checkpoint genes were found to be significantly different between the two groups, such as CTLA4, PD-L1, CD47, CD276, CXCL8, and HAVCR2/TIM3. Finally, the analysis of immunotherapy revealed that the efficacy of CTLA4 or PD1 blockers alone was better in the low-risk group than in the high-risk group. Taken together, we developed and validated a prognostic risk model based on 15 hub genes, which performed well in predicting prognosis and immunotherapy response of BCa patients.


Assuntos
Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/imunologia , Antígenos B7/genética , Biomarcadores Farmacológicos , Biomarcadores Tumorais/genética , Antígeno CTLA-4/genética , Expressão Gênica/genética , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Estimativa de Kaplan-Meier , Modelos Teóricos , Nomogramas , Prognóstico , Curva ROC , Fatores de Risco , Transcriptoma/genética , Microambiente Tumoral/genética , Bexiga Urinária/patologia
4.
Zhonghua Nan Ke Xue ; 27(9): 793-797, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34914254

RESUMO

Objective: To investigate the application of a simplified technique for reconstruction of vesicourethral support (RVUS) in laparoscopic radical prostatectomy (LRP). METHODS: From January 2017 to August 2019, 122 patients with localized prostate cancer underwent extraperitoneal LRP, 65 with RVUS (the RVUS group) and 57 without RVUS (the non-RVUS group). We compared the operation time, intraoperative blood loss, rate of pelvic lymph node dissection, neurovascular bundle sparing, incidence of urethrovesical anastomotic urinary leakage (UVAUL), postoperative urinary continence, postoperative hospital stay, intraperitoneal drainage tube removal time, and urethral catheter removal time between the two groups of patients. RESULTS: No statistically significant differences were observed between the two groups in the operation time, intraoperative blood loss, rate of pelvic lymph node dissection, neurovascular bundle sparing, or urethral catheter removal time (P > 0.05). The incidence rate of UVAUL was lower in the non-RVUS than in the RVUS group (8.8% vs 0%, P < 0.05), and so were the rates of postoperative urinary continence immediate after (0% vs 32.3%, P < 0.05) and at 1 month (38.6% vs 56.9%, P < 0.05), 3 months (59.6% vs 80%, P < 0.05), 6 months (78.9% vs 84.6%, P > 0.05) and 12 months after catheter removal (87.7% vs 92.3%, P > 0.05). The postoperative hospital stay was dramatically longer in the non-RVUS than in the RVUS group (ï¼»9.1 ± 4.3ï¼½ vs ï¼»6.7 ± 1.8ï¼½ d, P < 0.01) and so was the intraperitoneal drainage tube removal time (ï¼»6.9 ± 4.5ï¼½ vs ï¼»4.8 ± 1.5ï¼½ d, P < 0.01). CONCLUSIONS: The simplified technique for reconstruction of vesicourethral support in laparoscopic radical prostatectomy improves early urinary continence, especially immediate continence, decreases the incidence rate of urethrovesical anastomotic urinary leakage, and shortens the intraperitoneal drainage tube removal time and postoperative hospital stay.?


Assuntos
Laparoscopia , Prostatectomia , Humanos , Masculino
5.
Neoplasia ; 24(2): 86-97, 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34954451

RESUMO

The excessive accumulation of saturated fatty acids and cholesterol have been linked to prostate cancer (Pca). Here, we found that lipoproteins, apolipoproteins, triglycerides and free fatty acids are significantly higher in the peripheral blood of prostate cancer patients than in non-cancer patients. Furthermore, the expression of ACC1, FASN and HMGCR is significantly higher in prostate cancer tissues than that in non-cancer tissues, and positively correlated with the gleason score. Using genetically engineered mouse models, we found that in a mouse model of high grade prostatic intraneoplasia (HGPIN), a combination of fatty acid synthase (FASN) overexpression and cholesterol efflux pump (Abca1) knockout resulted in the progression of prostatic intraneoplasia (PIN) to invasive PCa with 100% penetrance, as well as an increase in prostate cancer stem cell (PCSC)population, accompanied by activation of PGE2 and TGF-ß signaling pathway. Our study suggests that the steady rise in prostate cancer incidence and mortality among Chinese population during the last several decades may be attribute to a combinational effect of fatty acid and cholesterol, and reduction in dietary fat and cholesterol intake could slow down the progression from occult lesions to prostate cancer.

6.
Adipocyte ; 10(1): 646-657, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34793269

RESUMO

Obesity and associated complications are becoming a pandemic. Inhibiting adipogenesis is an important intervention for the treatment of obesity. Despite intensive investigations, numerous mechanistic aspects of adipogenesis remain unclear, and many potential therapeutic targets have yet to be discovered. Transcriptomics and lipidomics approaches were used to explore the functional genes regulating adipogenic differentiation and the potential mechanism in OP9 cells and adipose-derived stem cells. In this study, we found that NADH:ubiquinone oxidoreductase subunit A6 (Ndufa6) participates in the regulation of adipogenic differentiation. Furthermore, we show that the effect of Ndufa6 is mediated through stearoyl-CoA desaturase 1 (Scd1) and demonstrate the inhibitory effect of a SCD1 inhibitor on adipogenesis. Our study broadens the understanding of adipogenic differentiation and offers NDUFA6-SCD1 as a potential therapeutic target for the treatment of obesity.

7.
Cancer Med ; 10(22): 8210-8221, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34569727

RESUMO

Circular RNAs (circRNAs) are novel biomarkers of various cancers. CircRNAs can sponge miRNAs and regulate target mRNAs, which was called competing endogenous RNAs (ceRNA). This study was designed to identify circRNAs related to patients with clear cell renal cell carcinoma (ccRCC) and the first to select three independent Gene Expression Omnibus microarrays covering circRNAs, miRNAs, and mRNAs for multiple analyses. The data of clinical cases applied in our study were obtained from The Cancer Genome Atlas. We successfully conducted a circRNA/miRNA/mRNA ceRNA network related to ccRCC patients via R software and Cytoscape including 8 circRNAs, 6 miRNAs, and 49 mRNAs. The prognosis-associated subnet covered 8 circRNAs, 6 miRNAs, and 22 mRNAs. Quantitative real-time PCR was applied to measure our prediction in three renal cell lines and 23 pairs of tissues. Small interfering RNA targeting the back-splice region of hsa_circ_0001167 was further implied to confirm the regulation. Ultimately, hsa_circ_0001167/hsa-miR-595/CCDC8 regulatory axis was identified in this study, which may serve as prognostic indicators. Lower levels of hsa_circ_0001167 and CCDC8 were potentially correlated with worse patient survival.

8.
Talanta ; 235: 122810, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34517667

RESUMO

MicroRNAs (miRNAs) are currently recognized as novel biomarkers for cancer early diagnosis, therapy selection, and progression monitoring. Herein, we developed an ultrasensitive and label-free homogeneous colorimetric strategy for miRNA detection based on engineering entropy-driven amplification (EDA) coupled with nicking enzyme-assisted AuNP aggregation. In our design, the target miRNA could specifically trigger the EDA recycling process. One of the EDA products could open the hairpin probe and form a dual strand containing a nicking endonuclease (Nb.BbvCl) cleavage region. After adding nicking endonuclease in the sensing solution, the product DNA fragments could act as two linkers, inducing the aggregation of ssDNA-modified AuNPs. Simultaneously, the liberating complementary strands continued to cyclic hybridization with the hairpin probe. This multiple signal amplification colorimetric strategy showed a wide linear range from 10 fM to 100 pM with a much lower detection limit of 3.13 fM for miRNA let-7a, which also performed well in a complex sample matrix. Most importantly, the naked eye could clearly distinguish the 10 fM color change caused by let-7a to be measured. Moreover, this approach could easily extend to multiple miRNAs with target-specific sequence substitutions. Therefore, this ultrasensitive visual strategy for miRNA demonstrated attractive potentials for promising applications in clinical diagnosis.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , MicroRNAs , Entropia , Ouro , Limite de Detecção , MicroRNAs/genética , Técnicas de Amplificação de Ácido Nucleico
9.
Front Immunol ; 12: 626217, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34276643

RESUMO

Alterations in the microbiome of the gut and oral cavity are involved in the etiopathogenesis of systemic lupus erythematosus (SLE). We aimed to assess whether both microbiome compositions in feces and saliva were specific in patients with SLE. A total of 35 patients with SLE, as well as sex- and age-matched asymptomatic subjects as healthy control (HC) group were recruited. Fecal swabs and saliva samples were collected from the participants. 16S ribosomal RNA gene sequencing was performed on the samples. Compared with the HC group, reduced bacterial richness and diversity were detected in the feces of patients with SLE, and increased bacterial diversity in their saliva. Both feces and saliva samples explained the cohort variation. The feces were characterized by enrichment of Lactobacillus, and depletion of an unclassified bacterium in the Ruminococcaceae family and Bifidobacterium. Lack of Bifidobacterium was observed in patients with arthritis. Akkermansia and Ruminococcus negatively correlated with the serum levels of C3. In saliva, Veillonella, Streptococcus, and Prevotella were dominant, and Bacteroides was negatively associated with disease activity. These findings can assist us to comprehensively understand the bacterial profiles of different body niches in SLE patients.


Assuntos
Bactérias/genética , Microbioma Gastrointestinal/genética , Lúpus Eritematoso Sistêmico/microbiologia , Microbiota/genética , Saliva/microbiologia , Adulto , Idoso , Bactérias/classificação , Estudos de Coortes , Fezes/microbiologia , Feminino , Microbioma Gastrointestinal/fisiologia , Variação Genética , Humanos , Masculino , Microbiota/fisiologia , Pessoa de Meia-Idade , Boca/microbiologia , Adulto Jovem
10.
Environ Toxicol Pharmacol ; 87: 103719, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34332081

RESUMO

Glucocorticoid-induced osteoporosis (GIOP) is a clinically important disease. Despite many studies, the intrinsic pathogenesis of GIOP is still not fully understood. Cartilage is the target tissue of the glucocorticoid prednisolone (PN). To explore the intrinsic mechanism of PN-induced cartilage damage, we performed cartilage staining and cell transfection experiments in zebrafish larvae treated with PN. The results showed that PN caused cartilage damage in zebrafish at 25 µM. Moreover, after treatment with PN, it was found that collagen-encoding gene expression was significantly reduced. Further research revealed that the glucocorticoid receptor (GR) mediates the transcriptional inhibition of collagen genes by PN. These results indicate that glucocorticoids cause cartilage damage by inhibiting the expression of collagen genes through their receptors. Our study provides new insights into GIOP.


Assuntos
Cartilagem/efeitos dos fármacos , Colágeno/genética , Regulação da Expressão Gênica/efeitos dos fármacos , Prednisolona/toxicidade , Animais , Cartilagem/anormalidades , Feminino , Células HEK293 , Humanos , Larva/efeitos dos fármacos , Larva/genética , Larva/crescimento & desenvolvimento , Masculino , Receptores de Glucocorticoides/genética , Peixe-Zebra/genética , Peixe-Zebra/crescimento & desenvolvimento
11.
Int J Clin Exp Pathol ; 14(4): 463-468, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33936368

RESUMO

BACKGROUND: Renal cyst is a common benign disease which is rare to progress from simple renal cyst to renal cell carcinoma. CASE PRESENTATION: A 62-year-old woman who suffered a simple renal cyst for over 20 years complained intermittent lumbar in recent 2 years. At her latest admission, the cyst lesion displayed enhancement in the cystic wall by CT scan and cystic to partially solid change by ultrasound, so we did a partial nephrectomy and found that the cystic lesion had become a cyst-solid transition. The pathology turned out to be renal clear cell carcinoma. CONCLUSIONS: Although the canceration of a renal cyst is a small probability event, patients with a long history of a cyst, especially those with symptoms, need to seek for medical treatment in time, and if necessary, lesion biopsy or resection may be under consideration.

12.
J Cell Mol Med ; 25(12): 5586-5601, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33982835

RESUMO

Alternative polarization of macrophages regulates multiple biological processes. While M1-polarized macrophages generally mediate rapid immune responses, M2-polarized macrophages induce chronic and mild immune responses. In either case, polyunsaturated fatty acid (PUFA)-derived lipid mediators act as both products and regulators of macrophages. Prostaglandin E3 (PGE3 ) is an eicosanoid derived from eicosapentaenoic acid, which is converted by cyclooxygenase, followed by prostaglandin E synthase successively. We found that PGE3 played an anti-inflammatory role by inhibiting LPS and interferon-γ-induced M1 polarization and promoting interleukin-4-mediated M2 polarization (M2a). Further, we found that although PGE3 had no direct effect on the growth of prostate cancer cells in vitro, PGE3 could inhibit prostate cancer in vivo in a nude mouse model of neoplasia. Notably, we found that PGE3 significantly inhibited prostate cancer cell growth in a cancer cell-macrophage co-culture system. Experimental results showed that PGE3 inhibited the polarization of tumour-associated M2 macrophages (TAM), consequently producing indirect anti-tumour activity. Mechanistically, we identified that PGE3 regulated the expression and activation of protein kinase A, which is critical for macrophage polarization. In summary, this study indicates that PGE3 can selectively promote M2a polarization, while inhibiting M1 and TAM polarization, thus exerting an anti-inflammatory effect and anti-tumour effect in prostate cancer.


Assuntos
Alprostadil/análogos & derivados , Anti-Inflamatórios/farmacologia , Diferenciação Celular , Inflamação/tratamento farmacológico , Ativação de Macrófagos/imunologia , Neoplasias da Próstata/tratamento farmacológico , Alprostadil/farmacologia , Animais , Polaridade Celular , Humanos , Inflamação/imunologia , Inflamação/patologia , Ativação de Macrófagos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Neoplasias da Próstata/imunologia , Neoplasias da Próstata/patologia , Transdução de Sinais
13.
Front Immunol ; 12: 609700, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33868230

RESUMO

Objectives: Gut dysbiosis is associated with chronic kidney disease (CKD), and serum free immunoglobulin light chains (FLCs) are biomarkers for CKD. This study aims to assess the CKD gut microbiome and to determine its impact on serum FLC levels. Methods: To control for confounders, 100 patients and sex- and age-matched healthy controls (HCs) were recruited. The gut microbiome was assessed by sequencing 16S rRNA gene V3-V4 hypervariable regions. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States was applied to infer functional metabolic pathways. When observing group differences in the microbiome and predicted metabolic pathways, demographic confounders were adjusted using binary logistic regression; when examining impacts of the gut microbiome and metabolic pathways on serum FLCs, factors influencing FLC levels were adjusted using multiple regression. Results: Principal coordinate analysis revealed a significantly different bacterial community between the CKD and HC groups (P < 0.05). After adjusting for confounders, lower Chao 1, observed species and Shannon indices based on binary logistic regression predicted CKD prevalence. Actinobacteria, Alistipes, Bifidobacterium and Bifidobacterium longum enrichment, upregulation of metabolic pathways of bacterial toxin, chloroalkane and chloroalkene degradation, and Staphylococcus aureus infection also predicted CKD prevalence (P < 0.05). Furthermore, depletion of Actinobacteria and Bifidobacterium and reduced chloroalkane and chloroalkene degradation predicted high levels of FLC λ (P < 0.05). Conclusions: Gut dysbiosis in CKD patients was confirmed by controlling for confounders in the present study. Additionally, the association between gut dysbiosis and FLC λ levels demonstrates the existence of crosstalk between the microbiome and immune response in CKD.


Assuntos
Disbiose , Microbioma Gastrointestinal , Cadeias Leves de Imunoglobulina/sangue , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/etiologia , Biomarcadores , Estudos de Casos e Controles , Biologia Computacional/métodos , Suscetibilidade a Doenças , Feminino , Taxa de Filtração Glomerular , Humanos , Testes de Função Renal , Masculino , Redes e Vias Metabólicas , Metagenoma , Metagenômica/métodos , Insuficiência Renal Crônica/diagnóstico , Índice de Gravidade de Doença
14.
Eur J Med Chem ; 219: 113407, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-33901805

RESUMO

Fatty acid synthase (FASN), the key enzyme in de novo lipogenesis, is an attractive therapeutic target for diseases characterized by excessive lipid accumulation. Many FASN inhibitors have failed in the clinical trial phase, largely because of poor solubility and safety. In this study, we generated a novel small-molecule FASN inhibitor by structure-based virtual screening. PFI09, the lead compound, is easy to synthesize, and inhibits the lipid synthesis in OP9 mammalian cell line and Caenorhabditis elegans as well as the proliferation of several cancer cell lines via the blockade of FASN. Mechanistic investigations show that PFI09 induces S-phase arrest, cell division reduction and apoptosis. We also develop a chemically stable analog of PFI09, MFI03, which reduces the proliferation of PC3 tumor cells both in vitro and in vivo, without toxicity to mice. In summary, our data suggest that MFI03 is an effective FASN inhibitor and a promising antineoplastic drug candidate.


Assuntos
Antineoplásicos/farmacologia , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Inibidores Enzimáticos/química , Ácido Graxo Sintases/antagonistas & inibidores , Animais , Antineoplásicos/química , Antineoplásicos/metabolismo , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Inibidores Enzimáticos/metabolismo , Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/uso terapêutico , Ácido Graxo Sintases/metabolismo , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/patologia , Pirrolidinas/química , Pirrolidinas/metabolismo , Pirrolidinas/farmacologia , Pirrolidinas/uso terapêutico
15.
BMC Microbiol ; 20(1): 336, 2020 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-33153435

RESUMO

BACKGROUND: The long-held notion that, without urinary tract or circulatory infection, bladder urine and blood are sterile biofluids has been disproven. There have been no previous reports on the kidney pelvis urinary microbiome after bladder disinfection in kidney stone patients. This study aimed to determine whether a kidney pelvis urinary microbiome is present after eliminating the influence of the bladder urinary microbiome, whether the microbiome composition is different in patients with stone kidney pelvis (SKP) and non-stone kidney pelvis (NSKP), and the correlation between SKP and patient clinical characteristics. RESULTS: Comparisons of bacterial diversity and community structure exhibited that urine in bladder was similar to SKP and NSKP. However, the comparisons showed that urine samples were different from blood. The most common operational taxonomic units were shared by all three types of urine samples. Corynebacterium was significantly higher in SKP compared to NSKP. Several bacteria were associated with patient characteristics, including Lactobacillus, which was positively correlated with fasting blood glucose, and Prevotella was negatively correlated with BMI. Lactobacillus was significantly higher in SKP compared to blood but not in NSKP compared to blood. CONCLUSIONS: The composition of the kidney pelvis urinary microbiome after disinfection of the bladder and its similarity to the bladder microbiome indicate that bladder urine can be used to replace kidney pelvis urine in microbiome research. Additionally, the comparison of SKP and NSKP and clinical associations suggest that the occurrence of kidney stones is responsible for the SKP urinary microbiome.


Assuntos
Cálculos Renais/microbiologia , Microbiota , Sistema Urinário/microbiologia , Adulto , Idoso , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Sangue/microbiologia , Feminino , Humanos , Rim/microbiologia , Rim/fisiologia , Cálculos Renais/fisiopatologia , Masculino , Pessoa de Meia-Idade , Pelve , RNA Ribossômico 16S/genética , Bexiga Urinária/microbiologia
16.
Front Immunol ; 11: 2138, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013903

RESUMO

Gut metabolites are products of the crosstalk between microbes and their host and play an important role in the occurrence, development, diagnosis, and treatment of autoimmune diseases. This work profiled the fecal metabolome of patients with systemic lupus erythematosus (SLE) using gas chromatography-mass spectrometry (GC-MS) and analyzed the potential roles of metabolites in the diagnosis and development of SLE. Fecal sample from 29 SLE patients without any other diseases and 30 healthy controls (HCs) were analyzed by metabolomics profiling. All participants took no antibiotics in the month before sampling and clinical data collecting. The metabolome profiles of patients with SLE and HCs were significantly different. Thirty fecal metabolites, such as deoxycholic acid, erucamide, L-tryptophan and putrescine, were significantly enriched, while nine metabolites, such as glyceric acid, γ-tocopherol, (Z)-13-octadecenoic acid and 2,4-di-tert-butylphenol, were depleted in SLE patients vs. HCs. The areas under the curve (AUCs) of L-valine, pyrimidine, erucamide, and L-leucine during ROC analysis were 0.886, 0.833, 0.829, and 0.803, indicating their good diagnostic potential. Moreover, the combination of L-valine, erucamide and 2,4-di-tert-butylphenol gave an AUC of 0.959. SLE-altered metabolites were significantly located in 28 pathways, such as ABC transporters (p = 3.40E-13) and aminoacyl-tRNA biosynthesis (p = 2.11E-12). Furthermore, SLE-altered fecal metabolites were closely correlated with SLE indicators, e.g., L-tryptophan was positively correlated with the SLEDAI-2K (p = 0.007). Our results suggest that the SLE fecal metabolome is closely associated with the occurrence and development of SLE and is of great diagnostic value.


Assuntos
Fezes/química , Cromatografia Gasosa-Espectrometria de Massas/métodos , Lúpus Eritematoso Sistêmico/metabolismo , Metabolômica/métodos , Adulto , Biomarcadores/metabolismo , Progressão da Doença , Ácidos Erúcicos/análise , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Fenóis/análise , Curva ROC , Valina/análise
17.
J Cell Physiol ; 235(12): 9729-9742, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32406953

RESUMO

Tumor-associated macrophages (TAMs) are vital constituents in mediating cell-to-cell communication within the tumor microenvironment. However, the molecular mechanisms underlying the interplay between TAMs and tumor cells that guide cell fate are largely undetermined. Extracellular vesicles, also known as exosomes, which are derived from TAMs, are the components exerting regulatory effects. Thus, understanding the underlying mechanism of "onco-vesicles" is of crucial importance for prostate cancer (PCa) therapy. In this study, we analyzed micro RNA sequences in exosomes released by THP-1 and M2 macrophages and found a significant increase in miR-95 levels in TAM-derived exosomes, demonstrating the direct uptake of miR-95 by recipient PCa cells. In vitro and in vivo loss-of-function assays suggested that miR-95 could function as a tumor promoter by directly binding to its downstream target gene, JunB, to promote PCa cell proliferation, invasion, and epithelial-mesenchymal transition. The clinical data analyses further revealed that higher miR-95 expression results in worse clinicopathological features. Collectively, our results demonstrated that TAM-mediated PCa progression is partially attributed to the aberrant expression of miR-95 in TAM-derived exosomes, and the miR-95/JunB axis provides the groundwork for research on TAMs to further develop more-personalized therapeutic approaches for patients with PCa.


Assuntos
MicroRNAs/genética , Neoplasias/genética , Neoplasias da Próstata/genética , Fatores de Transcrição/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Transição Epitelial-Mesenquimal/genética , Exossomos/genética , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Neoplasias/patologia , Neoplasias da Próstata/patologia , Microambiente Tumoral/genética , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/patologia
18.
J Cell Mol Med ; 24(14): 8045-8056, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32469149

RESUMO

Plastic polarization of macrophage is involved in tumorigenesis. M1-polarized macrophage mediates rapid inflammation, entity clearance and may also cause inflammation-induced mutagenesis. M2-polarized macrophage inhibits rapid inflammation but can promote tumour aggravation. ω-3 long-chain polyunsaturated fatty acid (PUFA)-derived metabolites show a strong anti-inflammatory effect because they can skew macrophage polarization from M1 to M2. However, their role in tumour promotive M2 macrophage is still unknown. Resolvin D1 and D2 (RvD1 and RvD2) are docosahexaenoic acid (DHA)-derived docosanoids converted by 15-lipoxygenase then 5-lipoxygenase successively. We found that although dietary DHA can inhibit prostate cancer in vivo, neither DHA (10 µmol/L) nor RvD (100 nmol/L) can directly inhibit the proliferation of prostate cancer cells in vitro. Unexpectedly, in a cancer cell-macrophage co-culture system, both DHA and RvD significantly inhibited cancer cell proliferation. RvD1 and RvD2 inhibited tumour-associated macrophage (TAM or M2d) polarization. Meanwhile, RvD1 and RvD2 also exhibited anti-inflammatory effects by inhibiting LPS-interferon (IFN)-γ-induced M1 polarization as well as promoting interleukin-4 (IL-4)-mediated M2a polarization. These differential polarization processes were mediated, at least in part, by protein kinase A. These results suggest that regulation of macrophage polarization using RvDs may be a potential therapeutic approach in the management of prostate cancer.


Assuntos
Antineoplásicos/farmacologia , Ácidos Docosa-Hexaenoicos/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Animais , Biomarcadores , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Humanos , Imuno-Histoquímica , Macrófagos/metabolismo , Camundongos , Camundongos Transgênicos , Transdução de Sinais/efeitos dos fármacos , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/imunologia , Macrófagos Associados a Tumor/metabolismo
19.
Oncol Rep ; 44(2): 747-756, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32468018

RESUMO

TAZ (transcriptional coactivator with PDZ­binding motif), which is also known as WW domain­containing transcription regulator 1 (WWTR1), a downstream effector of the Hippo pathway, has been reported to regulate cancer cell proliferation, migration and apoptosis by acting as a transcriptional coactivator. However, the function of TAZ in prostate cancer cells has not been investigated. In the present study, TAZ expression in prostate cancer (PCa) and benign prostatic hyperplasia tissues, PCa cell lines, and normal prostate epithelial cells was determined with the use of immunohistochemistry. TAZ was knocked down by shRNA in the PC3 cells, a prostate cancer cell line, and cell viability and migration assays were performed to determine the biological functions of TAZ. A mouse subcutaneous xenograft model was used to determine the in vivo effects of TAZ knockdown on tumor growth. We demonstrated that TAZ is overexpressed in PCa tissues, and the expression levels were found to be positively correlated with the Gleason scores of cancer grade. Moreover, TAZ knockdown inhibited PC3 cell proliferation, reduced cell migration, and induced apoptosis. Further experiments demonstrated that TAZ knockdown may lead to PC3 cell apoptosis through the exogenous apoptotic pathway by inducing the expression and cleavage of caspase­4 and ­7. In the tumor xenograft model, TAZ knockdown led to a decreased tumor growth rate. Taken together, the experimental results indicate that TAZ plays a significant role in the proliferation, migration and apoptosis of prostate cancer cells. TAZ could be a useful biomarker for PCa diagnosis/prognosis, and it could be a potential target for the treatment of prostate cancers.


Assuntos
Hiperplasia Prostática/metabolismo , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Transativadores/metabolismo , Regulação para Cima , Idoso , Idoso de 80 Anos ou mais , Animais , Apoptose , Estudos de Casos e Controles , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Gradação de Tumores , Transplante de Neoplasias , Células PC-3
20.
J Transl Med ; 18(1): 130, 2020 03 17.
Artigo em Inglês | MEDLINE | ID: mdl-32183836

RESUMO

BACKGROUND: Kidney stone disease (KSD) is more common in individuals with hypertension (HTN) than in individuals with normotension (NTN). Urinary dysbiosis is associated with urinary tract disease and systemic diseases. However, the role of the urinary microbiome in KSD complicated with HTN remains unclear. METHODS: This study investigated the relationship between the pelvis urinary microbiome and blood pressure (BP) in patients with KSD co-occurring with HTN (KSD-HTN) and healthy controls (HC) by conducting 16S rRNA gene sequencing of bacteria in urine samples. The urine samples were collected (after bladder disinfection) from 50 patients with unilateral kidney calcium stones and NTN (n = 12), prehypertension (pHTN; n = 11), or HTN (n = 27), along with 12 HCs. RESULTS: Principal coordinates analysis showed that there were significant differences in the urinary microbiomes not only between KSD patients and HCs but also between KSD-pHTN or KSD-HTN patients and KSD-NTN patients. Gardnerella dominated in HCs, Staphylococcus dominated in KSD-NTN patients and Sphingomonas dominated in both KSD-pHTN and KSD-HTN patients. The abundance of several genera including Acidovorax, Gardnerella and Lactobacillus was correlated with BP. Adherens junction and nitrogen and nucleotide metabolism pathways, among others, were associated with changes in BP. CONCLUSIONS: The findings suggest that patients with KSD complicated with HTN have a unique urinary microbiome profile and that changes in the microbiome may reflect disease progression and may be useful to monitor response to treatments.


Assuntos
Hipertensão , Cálculos Renais , Microbiota , Pressão Sanguínea , Humanos , Hipertensão/complicações , Cálculos Renais/complicações , RNA Ribossômico 16S/genética
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