RESUMO
Disease ontologies facilitate the semantic organization and representation of domain-specific knowledge. In the case of prostate cancer (PCa), large volumes of research results and clinical data have been accumulated and needed to be standardized for sharing and translational researches. A formal representation of PCa-associated knowledge will be essential to the diverse data standardization, data sharing and the future knowledge graph extraction, deep phenotyping and explainable artificial intelligence developing. In this study, we constructed an updated PCa ontology (PCAO2) based on the ontology development life cycle. An online information retrieval system was designed to ensure the usability of the ontology. The PCAO2 with a subclass-based taxonomic hierarchy covers the major biomedical concepts for PCa-associated genotypic, phenotypic and lifestyle data. The current version of the PCAO2 contains 633 concepts organized under three biomedical viewpoints, namely, epidemiology, diagnosis and treatment. These concepts are enriched by the addition of definition, synonym, relationship and reference. For the precision diagnosis and treatment, the PCa-associated genes and lifestyles are integrated in the viewpoint of epidemiological aspects of PCa. PCAO2 provides a standardized and systematized semantic framework for studying large amounts of heterogeneous PCa data and knowledge, which can be further, edited and enriched by the scientific community. The PCAO2 is freely available at https://bioportal.bioontology.org/ontologies/PCAO, http://pcaontology.net/ and http://pcaontology.net/mobile/.
Assuntos
Ontologias Biológicas , Neoplasias da Próstata , Humanos , Masculino , Inteligência Artificial , Semântica , Neoplasias da Próstata/genéticaRESUMO
Eukaryotic translation initiation factors (eIFs) are crucial for initiating protein translation and ensuring the correct assembly of mRNA-ribosomal subunit complexes. In this study, we investigated the effects of deleting six eIFs in the apicomplexan parasite Toxoplasma gondii using the CRISPR-Cas9 system. We determined the subcellular localization of these eIFs using C-terminal endogenous tagging and immunofluorescence analysis. Four eIFs (RH::315150-6HA, RH::286090-6HA, RH::249370-6HA, and RH::211410-6HA) were localized in the cytoplasm, while RH::224235-6HA was localized in the apicoplast. Additionally, RH::272640-6HA was found in both the basal complex and the cytoplasm of T. gondii. Functional characterization of the six RHΔeIFs strains was conducted using plaque assay, cell invasion assay, intracellular growth assay and egress assay in vitro, and virulence assay in mice. Disruption of five eIF genes (RHΔ315150, RHΔ272640, RHΔ249370, RHΔ211410, and RHΔ224235) did not affect the ability of the T. gondii RH strain to invade, replicate, form plaques and egress in vitro, or virulence in Kunming mice (p > 0.05). However, the RHΔ286090 strain showed slightly reduced invasion efficiency and virulence (p < 0.01) compared to the other five RHΔeIFs strains and the wild-type strain. The disruption of the TGGT1_286090 gene significantly impaired the ability of tachyzoites to differentiate into bradyzoites in both type I RH and type II Pru strains. These findings reveal that the eukaryotic translation initiation factor TGGT1_286090 is crucial for T. gondii bradyzoite differentiation and may serve as a potential target for drug development and an attenuated vaccine against T. gondii.
Assuntos
Sistemas CRISPR-Cas , Fatores de Iniciação em Eucariotos , Proteínas de Protozoários , Toxoplasma , Toxoplasma/genética , Toxoplasma/patogenicidade , Toxoplasma/metabolismo , Toxoplasma/crescimento & desenvolvimento , Animais , Camundongos , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismo , Fatores de Iniciação em Eucariotos/genética , Fatores de Iniciação em Eucariotos/metabolismo , Virulência/genética , Toxoplasmose/parasitologia , Toxoplasmose/genética , HumanosRESUMO
Several calcium-binding proteins including calcium-dependent protein kinases play important roles in several facets of the intracellular infection cycle of the apicomplexan protozoan parasite Toxoplasma gondii. However, the role of the calcium-binding epidermal growth factor (EGF) domain-containing proteins (CBDPs) remains poorly understood. In this study, we examined the functions of four CBDP genes in T. gondii RH strain of type I by generating knock-out strains using CRISPR-Cas9 system. We investigated the ability of mutant strains deficient in CBDP1, CBDP2, CBDP3, or CBDP4 to form plaques, replicate intracellularly, and egress from the host cells. The results showed that no definite differences between any of these four CBDP mutant strains and the wild-type strain in terms of their ability to form plaques, intracellular replication, and egress. Additionally, CBDP mutants did not exhibit any significant attenuated virulence compared to the wild-type strain in mice. The expression profiles of CBDP2-4 genes were conserved among T. gondii strains of different genotypes, life cycle stages, and developmental forms. Whether other CBDP genes play any roles in the pathogenicity of T. gondii strains of different genotypes remains to be elucidated.
Assuntos
Parasitos , Toxoplasma , Animais , Camundongos , Virulência , Parasitos/metabolismo , Fator de Crescimento Epidérmico/metabolismo , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Protozoários/genética , Proteínas de Protozoários/metabolismoRESUMO
In recent years, the benefits of carrots and carotene in different areas of health have been examined. The purpose of this umbrella review was to identify the associations between carrots and carotene and multiple health outcomes. The review considered evidence from meta-analyses of interventional and observational studies of carrots and carotene and any health outcome. We comprehensively searched Web of Science, PubMed, and Embase. For each association, we estimated the summary effect size using random and fixed effects models and the 95% confidence interval. A total of 1329 studies were searched, and 30 meta-analyses with 26 health outcomes were identified that met the eligibility criteria. Carrot intake was associated with a lower risk of multiple cancer outcomes including breast cancer, lung cancer, pancreatic cancer, gastric cancer, urothelial cancer, and prostate cancer. Carotene intake was associated with a lower risk of fracture, age-related cataract, sunburn, Alzheimer's disease, breast cancer, lung cancer, pancreatic cancer, gastric cancer, esophageal cancer, prostate cancer, and head and neck cancer (HNC). Serum carotene was inversely associated with all-cause mortality, breast cancer, and lung cancer. Our study revealed that carrot or carotene intake could reduce the risk of various negative health outcomes. © 2023 Society of Chemical Industry.
Assuntos
Neoplasias da Mama , Daucus carota , Neoplasias Gástricas , Masculino , Humanos , Carotenoides/análise , beta CarotenoRESUMO
Many biological species combine the helical organization of cellulose or chitin microfibrils with broadband light absorption of black melanin to produce brilliant structural colors with metallic and glossy effects and other diverse functions. In this work, based on core-shell CNC@PDA chiral nanorods consisting of cellulose nanocrystals (CNCs) as the core and melanin-like polydopamine (PDA) as the shell that can form well-defined chiral liquid crystal phases, we report chiral photonic materials that closely mimic the unique coloration mechanisms and functionalities mastered by several biological species. The photonic films formed by such single CNC@PDA nanorods have brilliant iridescent structural colors originating from selective reflection of circularly polarized lights by the helical organization of CNC@PDAs across the films. Furthermore, the colors of such films have background-independent brightness, high visibility, and metallic effects that arise from the light absorption of the PDA component. Especially, the color ranges and metallic effects of the films can be conveniently tuned by varying the thickness of the PDA shell. In addition, the UV absorption and hygroscopic properties of PDA endow these CNC@PDA films with efficient broadband UV shielding and sensitive humidity-induced dynamic color changes. Due to the mussel-like superior adhesion of PDA, CNC@PDA-based photonic coatings can be formed conformably onto diverse kinds of substrates. A shiny eye shadow with viewing angle-dependent colorful patterns was used to demonstrate the potential applications. With combinations of multiple unique properties in one photonic material fabricated from a single building block, these CNC@PDA-based films are expected to have potential applications in cosmetics, UV protection, anticounterfeiting, chiral reflectors, etc.
Assuntos
Cosméticos , Nanotubos , Biomimética , Celulose/química , Umidade , Melaninas/químicaRESUMO
BACKGROUND: Bisphenol A (BPA) exposure and its structural analogs (BPS and BPF) might cause endocrine alterations and adverse physiological effects. Few studies to date have directly explored the association between its structural analogs (BPS, BPF) and sex hormones in adult male participants. Therefore, we aimed to assess the associations between BPA, BPS, BPF, and sex hormones in American adult men. METHODS: We used data from the U.S. National Health and Nutrition Examination Survey 2011-2016. We excluded participants without data available on sex hormones and urinary bisphenols. Furthermore, participants consuming sex hormone medications were excluded. Multivariable regression models were performed to assess the association between bisphenols and sex hormones. RESULTS: In this study, 2367 participants were included. Of 2367, in 1575 participants, the data on BPS and BPF were available. We found that a per unit increase in BPF was associated with 0.575 ng/dL higher total testosterone (TT) (Model 2: 95% CI: 0.047, 1.103, P = 0.033). However, there was no significant association between BPA or BPS and TT. Furthermore, increased BPA and BPS levels were associated with higher levels of sex hormone-binding globulin (SHBG) (Model 2: ß = 0.364, 95% CI: 0.158, 0.571; ß = 0.25, 95% CI: 0.071, 0.429, respectively). Additionally, participants in the highest BPA exposure quartile (quartile 4) had 4.072 nmol/L higher levels of SHBG than those in quartile 1 (Model 2: 95% CI: 0.746, 7.397, P = 0.017; P for trend =0.005). Both BPA and BPS were negatively associated with free testosterone (FT, nmol/L) after full adjustment (Model 2, ß = - 0.01%, P = 0.0211, P = 0.0211; Model 2, ß = - 0.01%, P = 0.0258, respectively). However, BPF was positively associated with FT (Model 2, ß = 0.0029%, P = 0.0028). CONCLUSION: Our study indicated that exposure to both BPA and its substitutions could alter sex hormone levels. This finding supports the possibility that human exposure to bisphenols at environmental levels might affect the endogenous hormone balance.
Assuntos
Compostos Benzidrílicos , Testosterona , Adulto , Humanos , Masculino , Inquéritos Nutricionais , Hormônios Esteroides GonadaisRESUMO
Phosphatase and tensin homolog-long (PTEN-L) is a translational isoform of PTEN, which exists in both intracellular and extracellular locations. Previous studies demonstrated that PTEN-L could inhibit oncogenesis due to its lipid phosphatase activity. However, recent studies found that PTEN-L could promote the proliferation of some types of cancer cells. Moreover, as a protein phosphatase, PTEN-L can suppress mitophagy by counteracting PTEN-induced putative kinase protein 1 (PINK1)-Parkin-mediated ubiquitin phosphorylation, namely, PTEN-L is critical for exploring the mitophagy progression and the treatment of mitochondrial diseases. Accounting for the critical functions of PTEN-L, its antibody can be used for the treatment or prognosis of tumors and mitochondrial diseases. Currently, the commercial antibody of PTEN-L is not available. In our study, the recombinant PTEN-L protein was expressed in Escherichia coli BL21 and used as an antigen to immunize Japan's big-eared white rabbit for the preparation of polyclonal antibody. The PTEN-L protein can be captured by PTEN-L antibody specifically and effectively. Taken together, a PTEN_L antibody is a valuable tool for further exploring the function of PTEN-L in oncogenesis and mitochondrial diseases, and it would be a new choice for the prognosis or treatment of cancer and mitochondrial diseases.
Assuntos
PTEN Fosfo-Hidrolase , Proteínas Quinases , Animais , Anticorpos/metabolismo , Carcinogênese/metabolismo , Carcinogênese/patologia , Mitocôndrias/metabolismo , Mitofagia , PTEN Fosfo-Hidrolase/genética , Proteínas Quinases/metabolismo , Proteínas Quinases/farmacologia , CoelhosRESUMO
BACKGROUND: Klotho is a hormone that emerges as an antiaging biomarker. However, the influence of the dietary pattern's inflammatory potential on serum Klotho levels in human populations, especially in a general adult population, remains unknown. This study aimed to evaluate the relationship between the dietary inflammatory index (DII) and serum Klotho concentrations in individuals living in the United States. METHODS : From the 2007-2016 National Health and Nutrition Examination Survey database, data of participants who completed the full 24-h dietary history and underwent serum Klotho testing were analyzed. The association between DII and serum Klotho concentrations was estimated using multivariable linear regression models. We also conducted segmented regression model to examine the threshold effect of DII on serum Klotho concentrations. RESULTS: A total of 10,928 participants were included, with a median serum Klotho concentration of 805.20 pg/mL (IQR: 657.58 - 1001.12) and a median DII of 1.43 (IQR: - 0.16 - 2.82). Multivariable regression showed that participants with high DII scores were associated with low serum Klotho concentrations; when classifying DII into quartiles, after full adjustment, participants in DII quartiles 3 and 4 showed a decrease in Klotho levels (25.27 and 12.44 pg/ml, respectively) compared with those in the lowest quartile (quartile 1) (95% CI: - 41.80, - 8.73 and - 29.83, 4.95, respectively; P for trend = 0.036). The segmented regression showed that the turning point value of DII was - 1.82 (95% CI: - 2.32, - 0.80). A 1-unit increase in DII was significantly associated with lower Klotho levels by - 33.05 (95% CI: - 52.84, - 13.27; P = 0.001) when DII ranges from - 5.18 to - 1.82; however, the relationship was not significant when DII ranges from - 1.82 to 5.42 (P > 0.05). Furthermore, stratified analyses indicated that the observed associations between DII and serum Klotho concentration were stronger among those aged ≥ 56 years, those with normal weight, and those without chronic kidney disease (P for interaction = 0.003, 0.015, and 0.041, respectively). CONCLUSIONS: In summary, we indicated that there was a dose-response relationship between DII and serum Klotho concentrations, suggesting that adhering to an anti-inflammatory diet has beneficial effects on aging and health by increasing the serum Klotho concentration.
Assuntos
Dieta , Inflamação , Biomarcadores , Estudos Transversais , Humanos , Inflamação/diagnóstico , Inflamação/epidemiologia , Inquéritos Nutricionais , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
Current treatment strategy for kidney renal clear cell carcinoma (KIRC) is limited. Tumor-associated antigens, especially neoantigen-based personalized mRNA vaccines represent new strategies and manifest clinical benefits in solid tumors, but only a small proportion of patients could benefit from them, which prompts us to identify effective antigens and suitable populations to facilitate mRNA vaccines application in cancer therapy. Through performing expression, mutation, survival and correlation analyses in TCGA-KIRC dataset, we identified four genes including DNA topoisomerase II alpha (TOP2A), neutrophil cytosol factor 4 (NCF4), formin-like protein 1 (FMNL1) and docking protein 3 (DOK3) as potential KIRC-specific neoantigen candidates. These four genes were upregulated, mutated and positively associated with survival and antigen-presenting cells in TCGA-KIRC. Furthermore, we identified two immune subtypes, named renal cell carcinoma immune subtype 1 (RIS1) and RIS2, of KIRC. Distinct clinical, molecular and immune-related signatures were observed between RIS1 and RIS2. Patients of RIS2 had better survival outcomes than those of RIS1. Further comprehensive immune-related analyses indicated that RIS1 is immunologically "hot" and represent an immunosuppressive phenotype, whereas RIS2 represents an immunologically "cold" phenotype. RIS1 and RIS2 also showed differential features with regard to tumor infiltrating immune cells and immune checkpoint-related genes. Moreover, the immune landscape construction identified the immune cell components of each KIRC patient, predicted their survival outcomes, and assisted the development of personalized mRNA vaccines. In summary, our study identified TOP2A, NCF4, FMNL1 and DOK3 as potential effective neoantigens for KIRC mRNA vaccine development, and patients with RIS2 tumor might benefit more from mRNA vaccination.
Assuntos
Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/imunologia , Carcinoma de Células Renais/imunologia , Carcinoma de Células Renais/terapia , Desenvolvimento de Vacinas , Vacinas de mRNA/imunologia , Antígenos de Neoplasias/genética , Biomarcadores Tumorais , Vacinas Anticâncer/genética , Carcinoma de Células Renais/genética , Biologia Computacional , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Imunidade , Imunomodulação/genética , MutaçãoRESUMO
Prostate adenocarcinoma (PRAD) is a leading cause of death among men. Messenger ribonucleic acid (mRNA) vaccine presents an attractive approach to achieve satisfactory outcomes; however, tumor antigen screening and vaccination candidates show a bottleneck in this field. We aimed to investigate the tumor antigens for mRNA vaccine development and immune subtypes for choosing appropriate patients for vaccination. We identified eight overexpressed and mutated tumor antigens with poor prognostic value of PRAD, including KLHL17, CPT1B, IQGAP3, LIME1, YJEFN3, KIAA1529, MSH5 and CELSR3. The correlation of those genes with antigen-presenting immune cells were assessed. We further identified three immune subtypes of PRAD (PRAD immune subtype [PIS] 1-3) with distinct clinical, molecular, and cellular characteristics. PIS1 showed better survival and immune cell infiltration, nevertheless, PIS2 and PIS3 showed cold tumor features with poorer prognosis and higher tumor genomic instability. Moreover, these immune subtypes presented distinguished association with immune checkpoints, immunogenic cell death modulators, and prognostic factors of PRAD. Furthermore, immune landscape characterization unraveled the immune heterogeneity among patients with PRAD. To summarize, our study suggests KLHL17, CPT1B, IQGAP3, LIME1, YJEFN3, KIAA1529, MSH5 and CELSR3 are potential antigens for PRAD mRNA vaccine development, and patients in the PIS2 and PIS3 groups are more suitable for vaccination.
Assuntos
Adenocarcinoma/imunologia , Antígenos de Neoplasias/imunologia , Vacinas Anticâncer/imunologia , Neoplasias da Próstata/imunologia , Vacinas Sintéticas/imunologia , Vacinas de mRNA/imunologia , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Biomarcadores Tumorais , Vacinas Anticâncer/uso terapêutico , Biologia Computacional/métodos , Mapeamento de Epitopos , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Masculino , Neoplasias da Próstata/patologia , Neoplasias da Próstata/terapia , Reprodutibilidade dos Testes , Transcriptoma , Vacinas Sintéticas/uso terapêutico , Vacinas de mRNA/uso terapêuticoRESUMO
BACKGROUND: Prostate cancer (PCa) is a leading cause of death in men, and effective treatment of PCa requires further development. Our study aimed to investigate the potential role of vinculin (VCL) in PCa progression in vitro and in vivo. METHODS: We investigated the methylation level of the VCL promoter based on the TCGA database. The knockdown efficacy of VCL gene expression was confirmed by quantitative polymerase chain reaction, Western blot analysis, and immunofluorescence. Furthermore, morphological changes in PCa cells were detected using phalloidin staining. The mobility of PCa cells was measured using transwell assays and high-content analysis. Moreover, cell growth and viability were determined using the colony formation and cell counting kit-8 assays. The role of VCL in tumor growth in vivo was investigated using a subcutaneous xenograft model generated by injecting tumor cells into the right flank of BALB/c nude mice. RESULTS: The methylation level of the VCL promoter in PCa was significantly downregulated concomitant with age and the progression of nodal metastasis. VCL expression was markedly decreased by shRNA. Importantly, VCL knockdown significantly changed the cell morphology; inhibited the migration, invasion, and movement; and repressed colony formation and viability of PCa cells in vitro. Furthermore, downregulation of VCL suppressed tumor growth in vivo. CONCLUSIONS: Our study comprehensively evaluated the role of VCL in PCa progression in vivo and in vitro. The findings of the present study suggest that VCL can be a potential target for PCa prognosis and treatment.
Assuntos
Neoplasias da Próstata/genética , Vinculina/genética , Animais , Movimento Celular , Proliferação de Células , Modelos Animais de Doenças , Progressão da Doença , Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Invasividade Neoplásica , Metástase Neoplásica , Transplante de Neoplasias , Processos Neoplásicos , Neoplasias da Próstata/patologia , Neoplasias da Próstata/fisiopatologia , Neoplasias da Próstata/secundárioRESUMO
PURPOSE: This study investigated the association between Dietary Inflammatory Index and sex hormones in a large, nationally representative adult male sample. MATERIALS AND METHODS: We utilized data from the 2013-2014 and 2015-2016 National Health and Nutrition Examination Survey. Males aged ≥20 years who provided a 24-hour dietary intake history and underwent serum sex hormone testing were included in analysis. Weighted proportions and multivariable analysis controlling for age, race, energy, smoking status, education level, body mass index and time of venipuncture were used to evaluate the associations between Dietary Inflammatory Index and sex hormones. RESULTS: For 4,151 participants, Dietary Inflammatory Index ranged from -5.05 to 5.48. Mean±SD total testosterone was 419.30±176.27 ng/dl. Mean±SD total testosterone was lower among men in the highest tertile compared with men in the lowest tertile group (410.42±171.97 vs 422.71±175.69, p <0.001). A per unit increase in Dietary Inflammatory Index was related to 4.0% (95% CI 0.5-7.6) higher odds of testosterone deficiency. In the fully adjusted multivariable model, males in Dietary Inflammatory Index tertile 3 (the most pro-inflammatory) had 29.6% (3.1-63.0) higher odds of testosterone deficiency than those in tertile 1 (p trend=0.025). Interaction tests revealed no significant effect of body mass index on the association of Dietary Inflammatory Index with testosterone deficiency and all sex hormone parameters. CONCLUSIONS: Men adhering to a more pro-inflammatory diet appear to have a higher risk of testosterone deficiency, indicating the important role of diet in male reproductive health.
Assuntos
Dieta , Hormônios Esteroides Gonadais/sangue , Inflamação/sangue , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Estados UnidosRESUMO
BACKGROUND: Inflammation is crucial in the pathogenesis of lower urinary tract symptoms (LUTS) in men. Diet modulates inflammation. Therefore, diet could be a modifiable factor in male LUTS prevention and treatment. We aimed to investigate the association between dietary inflammatory potential and male LUTS. METHODS: We used two cycles of National Health and Nutrition Examination Survey (NHANES) with self-report LUTS data. We calculated the dietary inflammatory index (DII) based on a 24 h diet recall and evaluated male LUTS. Clinical LUTS was defined as two or more coexisting symptoms. We used univariate and multivariate logistic regression models, the smooth curve fitting to analyze the relationship between clinical LUTS and the DII score. Subgroup analyses were conducted. RESULTS: We observed a positive non-linear relationship between clinical LUTS and DII. We found that when DII was higher than the inflection point 2.39, a 1-unit increase in DII was associated with 26.1% higher adjusted odds of clinical LUTS. Subgroup analyses showed that the DII score was only positively correlated with clinical LUTS risk in non-drinkers, smokers, and non-obese people (DII >2.39). CONCLUSIONS: Inflammation might be the key mechanism bridging dietary consumption to male LUTS. Excessive pro-inflammatory food intake (DII >2.39) warrants special vigilance, especially for non-drinkers, smokers, and non-obese men.
Assuntos
Dieta , Sintomas do Trato Urinário Inferior , Estudos Transversais , Humanos , Inflamação/epidemiologia , Inflamação/etiologia , Sintomas do Trato Urinário Inferior/epidemiologia , Sintomas do Trato Urinário Inferior/etiologia , Masculino , Inquéritos Nutricionais , Fatores de Risco , Estados Unidos/epidemiologiaRESUMO
Objective: Studies have showed that different follow-up starting points might potentially impact the comparison between primary (PMIBC) and secondary muscle-invasive bladder cancer (SMIBC), but the only previous meta-analysis did not differentiate the follow-up starting points of included studies. With more trials published, we aim to update the meta-analysis comparing PMIBC and SMIBC. Methods: PubMed, Embase, Cochrane Library and ClinicalTrial.gov. systematically searched. Literatures comparing the survival outcomes of PMIBC and SMIBC were selected. Outcomes of cancer-specific mortality (CSM), overall mortality (OM) and recurrence-free survival (RFS) were pooled and grouped based on the starting point of follow-up (after initial diagnosis or radical cystectomy (RC)). Newcastle-Ottawa Scale (NOS) and funnel plot were employed to assess the study quality and publication bias, respectively. Results: A total of 17 high-quality studies were selected, with 5558 patients aged from 59.8 to 72.7 (mean value) involved. The male-to-female ratio was roughly 4:1 (4390/1124). SMIBC had lower risk of CSM after initial diagnosis (HR 0.81, 95%CI 0.67-0.98, P=0.03, I2=70%), but higher risk of CSM after RC (HR 1.45, 95%CI 1.27-1.65, P<0.00001, I2=64%). In terms of OM and recurrence, outcomes were pooled only after RC, which both turned out to be higher for SMIBC (OM: HR 1.50, 95%CI 1.30-1.73, P<0.00001, I2=0%; Recurrence: HR 1.66, 95%CI 1.36-2.02, P<0.00001, I2=48%). No obvious publication bias was observed from funnel plot. Conclusion: The current study suggested SMIBC had higher risk of CSM, OM and recurrence after RC, but lower risk of CSM after initial diagnosis.
Assuntos
Músculo Liso/patologia , Recidiva Local de Neoplasia/epidemiologia , Neoplasias da Bexiga Urinária/mortalidade , Bexiga Urinária/patologia , Cistectomia , Progressão da Doença , Intervalo Livre de Doença , Seguimentos , Humanos , Músculo Liso/cirurgia , Invasividade Neoplásica/patologia , Bexiga Urinária/cirurgia , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/cirurgiaRESUMO
OBJECTIVE: We evaluate the association between the Dietary Inflammatory Index (DII) and kidney stones. DESIGN: We performed a cross-sectional analysis using data from National Health and Nutrition Examination Survey (NHANES). Dietary intake information was assessed using first 24-h dietary recall interviews, and the Kidney Conditions were presented by a questionnaire. The primary outcome was to investigate the association between DII and incidence of kidney stones, and the secondary outcome was to assess the association between DII and nephrolithiasis recurrence. SETTING: The NHANES, 2007-2016. PARTICIPANTS: The study included 25 984 NHANES participants, whose data on DII and kidney stones were available, of whom 2439 reported a history of kidney stones. RESULTS: For the primary outcome, after fully multivariate adjustment, DII score is positively associated with the risk of kidney stones (OR = 1·07; 95 % CI 1·04, 1·10). Then, compared Q4 with Q1, a significant 38 % increased likelihood of nephrolithiasis was observed. (OR = 1·38; 95 % CI 1·19, 1·60). For the secondary outcome, the multivariate regression analysis showed that DII score is positively correlated with nephrolithiasis recurrence (OR = 1·07; 95 % CI 1·00, 1·15). The results noted that higher DII scores (Q3 and Q4) are positively associated with a significant 48 % and 61 % increased risk of nephrolithiasis recurrence compared with the reference after fully multivariate adjustment (OR = 1·48; 95 % CI 1·07, 2·05; OR = 1·61; 95 % CI 1·12, 2·31). CONCLUSIONS: Our findings revealed that increased intake of pro-inflammatory diet, as a higher DII score, is correlated with increased odds of kidney stones incidence and recurrence.
Assuntos
Inflamação , Cálculos Renais , Adulto , Estudos Transversais , Dieta/efeitos adversos , Humanos , Inflamação/diagnóstico , Inflamação/epidemiologia , Cálculos Renais/epidemiologia , Cálculos Renais/etiologia , Inquéritos Nutricionais , Fatores de RiscoRESUMO
BACKGROUND: Controversy remains despite several studies have discussed the role of bariatric surgery in improving male's sexual function. This study aims to evaluate the efficacy of bariatric surgery in promoting male's erectile function. METHODS: PubMed, EMbase, The Cochrane Library, CNKI and Clinical Trails.gov were searched from database inception to May 2019. The language of publication was limited in English. The International Index of Erectile Function (IIEF) score and Brief Male Sexual Function Inventory (BSFI) score were set as the primary outcome. RESULTS: Eleven studies with a total of 370 patients were enrolled in this meta-analysis. The results showed significant improvement in the IIEF score (erectile function: MD = 5.33, 95% CI 4.12-6.54; intercourse satisfaction: MD = 2.57, 95% CI 1.19-3.94; orgasmic function: MD = 0.50, 95%CI 0.60-0.94; overall satisfaction: MD = 1.67, 95% CI 0.78-2.56; sexual desire: MD = 1.27, 95% CI 0.61-1.93; total erectile function: MD = 7.21, 95% CI 4.33-10.10) and the BSFI score (erection: MD =2.53, 95% CI 2.39-2.67; ejaculation: MD = 1.40, 95% CI 1.28-1.51; desire: MD =1.40, 95% CI 1.32-1.49; problem assessment: MD = 2.20, 95% CI 2.06-2.34; sexual satisfaction: MD = 0.70, 95% CI 0.60-0.76) in obese individuals after bariatric surgery. CONCLUSIONS: This systematic review and meta-analysis indicated that bariatric surgery could be effective in promoting males's sexual function for obese individuals.
Assuntos
Cirurgia Bariátrica , Disfunção Erétil/terapia , Obesidade Mórbida/cirurgia , Ereção Peniana/fisiologia , Disfunção Erétil/etiologia , Medicina Baseada em Evidências , Humanos , Masculino , Obesidade Mórbida/complicações , Resultado do TratamentoRESUMO
This study aims to compare the efficacy and safety of holmium laser technologies (HoL-Ts) and photoselective greenlight vaporization (PVP) for the treatment of benign prostatic hyperplasia (BPH), and to perform a meta-analysis according to the Preferred Reporting Items of Systematic Reviews and Meta-Analyses guidelines on PubMed, EMBASE, ClinicalTrial.gov, and the Cochrane Central Register of Controlled Trials up to August 2019. Functional outcomes, perioperative parameters, and complications were included and analyzed. Review Manager 5.3 (Cochrane Collaboration, Oxford, UK) was used to perform all analyses. A total of six articles composed of 2014 patients were included in this review. In comparison with PVP, HoL-Ts had a better performance in 1-, 3-, and 6-month Qmax (P = 0.02, but I2 = 81%), with less postvoid residual urine volume (PVR) (MD = -33.85, 95% CI -52.13 to -15.57, P = 0.0003) and less total energy used (MD = -31.66, 95% CI -58.99 to -4.33, P = 0.02). Moreover, HoL-Ts had a relatively lower risk of conversion rate (OR = 0.08, 95% CI 0.01 to 0.60, P = 0.01) associated with enough enucleation and less intraoperative bleeding. Subgroup analysis of holmium laser enucleation of prostate (HoLEP) versus PVP suggested that HoLEP presented better results in 1-, 3-, 6-month and 1-year Qmax with less PVR, less energy consumption, and lower conversion rate. Compared with PVP, HoL-Ts had higher 1-, 3-, and 6-month Qmax, less PVR, and less total energy consumption with a relatively lower risk of conversion rate. In subgroup analyses, HoLEP had shown better results in accordance with all HoL-Ts. Nevertheless, well-designed RCTs including overall functional indicators are required to confirm our findings.
Assuntos
Lasers de Estado Sólido/uso terapêutico , Hiperplasia Prostática/cirurgia , Idoso , Humanos , Lasers de Estado Sólido/efeitos adversos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Qualidade de Vida , Ressecção Transuretral da Próstata , Resultado do Tratamento , VolatilizaçãoRESUMO
The tumor microenvironment is associated with various tumor progressions, including cancer metastasis, immunosuppression, and tumor sustained growth. Tumor-associated macrophages (TAMs) are considered an indispensable component of the tumor microenvironment, participating in the progression of tumor microenvironment remodeling and creating various compounds to regulate tumor activities. This study aims to observe enriched TAMs in tumor tissues during bladder cancer development, which markedly facilitated the proliferation of bladder cancer cells and promoted tumor growth in vivo. We determined that TAMs regulate tumor sustained growth by secreting type I collagen, which can activate the prosurvival integrin α2ß1/PI3K/AKT signaling pathway. Furthermore, traditional chemotherapeutic drugs combined with integrin α2ß1 inhibitor showed intensive anticancer effects, revealing an innovative approach in clinical bladder cancer treatment.
Assuntos
Cromonas/administração & dosagem , Colágeno/metabolismo , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Macrófagos/patologia , Morfolinas/administração & dosagem , Transdução de Sinais/efeitos dos fármacos , Neoplasias da Bexiga Urinária/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Proliferação de Células , Cromonas/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Compostos Heterocíclicos com 3 Anéis/farmacologia , Humanos , Integrina alfa2beta1/genética , Integrina alfa2beta1/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Morfolinas/farmacologia , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Microambiente Tumoral , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
The 3D cell spheroid is an emerging tool that allows better recapitulating of in vivo scenarios with multiple factors such as tissue-like morphology and membrane protein expression that intimately coordinates with enzyme activity, thus providing a psychological environment for tumorigenesis study. For analyzing different spheroids, conventional optical imaging may be hampered by the need for fluorescent labeling, which could cause toxicity side effects. As an alternative approach, scanning electrochemical microscopy (SECM) enables label-free imaging. However, SECM for cell spheroid imaging is currently suffering from incapability of systematically analyzing the cell aggregates from spheroid generation, electrochemical signal gaining, and the gene expression on different individual cell spheroids. Herein, we developed a top-removable microfluidic device for cell aggregate yielding and SECM imaging methodology to analyze heterotypic 3D cell spheroids on a single device. This technique allows not only on-chip culturing of cell aggregates but also SECM imaging of the spheroids after opening the chip and subsequent qPCR assay of corresponding clusters. Through employment of the micropit arrays (85 × 4) with a top withdrawable microfluidic layer, uniformly sized breast tumor cell and fibroblast spheroids can be simultaneously produced on a single device. By leveraging voltage-switching mode SECM at different potentials of dual mediators, we evaluated alkaline phosphatase without disturbance of substrate morphology for distinguishing the tumor aggregates from stroma. Moreover, this method also enables gene expression profiling on individual tumor or stromal spheroids. Therefore, this new strategy can seamlessly bridge SECM measurements and molecular biological analysis.
Assuntos
Fosfatase Alcalina/análise , Dispositivos Lab-On-A-Chip , Técnicas Analíticas Microfluídicas/métodos , Microscopia Eletroquímica de Varredura/métodos , Esferoides Celulares/química , Fosfatase Alcalina/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Técnicas de Cultura de Células/instrumentação , Técnicas de Cultura de Células/métodos , Fibroblastos/química , Perfilação da Expressão Gênica , Humanos , Células MCF-7 , Técnicas Analíticas Microfluídicas/instrumentação , Estudo de Prova de Conceito , RNA Mensageiro/análise , Reação em Cadeia da Polimerase em Tempo RealRESUMO
BACKGROUND: Previous study compared limited number of parameters post the treatment of cold knife and laser urethrotomy for urethral stricture and controversy about the superiority of those two techniques still remains. This study aims to update the evidence and provide better clinical guidance. METHOD: We systematically searched Pubmed, Embase, ClinicalTrial.gov, and Cochrane Library Central Register of Controlled Trials for articles comparing cold knife and laser urethrotomy for urethral stricture. Parameters including maximum urinary flow (Qmax), recurrence, reoperation, complications, operation time, and Visual Analog Scale (VAS) pain score were compared using RevMan 5.3. RESULTS: Seven articles involving 453 patients were eventually included. The cold-knife group had better 6-month Qmax (MD - 0.95, 95% CI - 1.49 to - 0.41) and similar 3-month and 12-month Qmax compared with the laser group. No significance was observed regarding the comparison of recurrence rate. The laser group had lower risk of bleeding (OR 0.08, 95% CI 0.01-0.43), lower rate of reoperation (OR 0.39, 95% CI 0.19-0.81) and longer operation time (MD 4.09, 95% CI 3.35-4.82). There was no significant difference in terms of other complications and VAS pain score. CONCLUSION: Cold knife and laser urethrotomy had similar efficacy regarding short-term and long-term recurrence rate and Qmax, except that the cold-knife group had slightly better 6-month Qmax. However, the laser group had less risk of bleeding and lower rate of reoperation but also longer operation time.