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BACKGROUND: Gastric cancer is a leading cause of cancer-related deaths influenced by both genetic and environmental factors. Triphenyl phosphate (TPP) is a prevalent flame retardant, but its health implications remain to be thoroughly understood. OBJECTIVE: To explore the link between TPP exposure and gastric cancer by examining gene expression patterns and developing a predictive model. METHODS: Gene expression data were sourced from The Cancer Genome Atlas (TCGA) and the Comparative Toxicogenomics Database (CTD). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were employed for analysis. Single-sample Gene Set Enrichment Analysis (ssGSEA) was used to obtain phosphate flame retardant-related scores. A predictive model was constructed through differential analysis, univariate COX regression, and LASSO regression. Molecular docking was performed to assess protein interactions with TPP. RESULTS: ssGSEA identified scores related to phosphate flame retardants in gastric cancer, which had a strong association with immune-related traits. Several genes associated with TPP were identified and used to develop a prognostic model that has clinical significance. Molecular docking showed a high binding affinity of TPP with MTTP, a gene related to lipid metabolism. Pathway analysis indicated that TPP exposure contributes to gastric cancer through lipid metabolic processes. CONCLUSION: The study establishes a potential correlation between TPP exposure and gastric cancer onset, pinpointing key genes and pathways involved. This underscores the significance of environmental factors in gastric cancer research and presents a potential diagnostic tool for clinical application.
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Movimento Celular , Proliferação de Células , Retardadores de Chama , Simulação de Acoplamento Molecular , Organofosfatos , Neoplasias Gástricas , Neoplasias Gástricas/genética , Neoplasias Gástricas/induzido quimicamente , Neoplasias Gástricas/patologia , Humanos , Organofosfatos/toxicidade , Retardadores de Chama/toxicidade , Proliferação de Células/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacosRESUMO
Background: The interaction between environmental endocrine-disrupting chemicals, such as Bisphenol A (BPA), and their influence on cancer progression, particularly regarding the GOLPH3 gene in colorectal cancer, remains unclear. Methods: We performed an integrated analysis of transcriptional profiling, clinical data, and bioinformatics analyses utilizing data from the Comparative Toxicogenomics Database and The Cancer Genome Atlas. The study employed ClueGO, Gene Set Enrichment Analysis, and Gene Set Variation Analysis for functional enrichment analysis, alongside experimental assays to examine the effects of BPA exposure on colorectal cancer cell lines, focusing on GOLPH3 expression and its implications for cancer progression. Results: Our findings demonstrated that BPA exposure significantly promoted the progression of colorectal cancer by upregulating GOLPH3, which in turn enhanced the malignant phenotype of colorectal cancer cells. Comparative analysis revealed elevated GOLPH3 protein levels in cancerous tissues versus normal tissues, with single-cell analysis indicating widespread GOLPH3 presence across various cell types in the cancer microenvironment. GOLPH3 was also associated with multiple carcinogenic pathways, including the G2M checkpoint. Furthermore, our investigation into the colorectal cancer microenvironment and genomic mutation signature underscored the oncogenic potential of GOLPH3, exacerbated by BPA exposure. Conclusion: This study provides novel insights into the complex interactions between BPA exposure and GOLPH3 in the context of colorectal cancer, emphasizing the need for heightened awareness and measures to mitigate BPA exposure risks. Our findings advocate for further research to validate these observations in clinical and epidemiological settings and explore potential therapeutic targets within these pathways.
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Ferroptosis is a novel form of programmed cell death and is considered to be a druggable target for colorectal cancer (CRC) therapy. However, the role of ferroptosis in CRC and its underlying mechanism are not fully understood. In the present study we found that a protein enriched in the Golgi apparatus, Golgi phosphoprotein 3 (GOLPH3), was overexpressed in human CRC tissue and in several CRC cell lines. The expression of GOLPH3 was significantly correlated with the expression of ferroptosis-related genes in CRC. The overexpression of GOLPH3 in Erastin-induced Caco-2 CRC cells reduced ferroptotic phenotypes, whereas the knockdown of GOLPH3 potentiated ferroptosis in HT-29 CRC cells. GOLPH3 induced the expression of prohibitin-1 (PHB1) and prohibitin-2 (PHB2), which also inhibited ferroptosis in Erastin-treated CRC cells. Moreover, GOLPH3 interacted with PHB2 and nuclear factor erythroid 2-related factor 2 (NRF2) in Caco-2 cells. These observations indicate that GOLPH3 is a negative regulator of ferroptosis in CRC cells. GOLPH3 protects these cells from ferroptosis by inducing the expression of PHB1 and PHB2, and by interacting with PHB2 and NRF2.
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Neoplasias Colorretais , Ferroptose , Proteínas de Membrana , Piperazinas , Proibitinas , Proteínas Repressoras , Humanos , Ferroptose/efeitos dos fármacos , Neoplasias Colorretais/metabolismo , Neoplasias Colorretais/patologia , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Células CACO-2 , Piperazinas/farmacologia , Proteínas Repressoras/metabolismo , Proteínas Repressoras/genética , Fator 2 Relacionado a NF-E2/metabolismo , Linhagem Celular Tumoral , Células HT29 , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacosRESUMO
BACKGROUND: 5-fluorouracil (5-FU) is conventionally used in chemotherapy for colon adenocarcinomas. Acquired resistance of 5-FU remains a clinical challenge in colon cancer, and efforts to develop targeted agents to reduce resistance have not yielded success. Protosappanin B (PSB), the main component of Lignum Sappan extract, is known to exhibit anti-tumor effects. However, whether and how PSB could improve 5-FU resistance in colon cancer have not yet been established. In this study, we aimed to explore the effects and underlying mechanisms of PSB in 5-FU-induced chemoresistance in colon adenocarcinoma. METHODS: Forty-seven paired colon cancer tissue samples from patients who received 5-FU chemotherapy were collected as clinical samples. Two 5-FU resistant colon cancer cell lines were established for in vitro experiments. Reverse transcription-quantitative PCR (RT-qPCR) was performed to determine the mRNA and microRNA (miRNA) expression levels in colon adenocarcinoma tissues and cell lines. Cell Counting Kit-8 (CCK-8) and flow cytometry assays were performed to evaluate cell proliferation and apoptosis, respectively. RESULTS: LINC00612 was highly expressed in colon adenocarcinoma samples and 5-FU resistant colon cancer cells. LINC00612 knockdown enhances 5-FU chemosensitivity in 5-FU resistant cells. Notably, PSB treatment attenuated LINC00612 expression in 5-FU resistant colon adenocarcinoma cells. Moreover, PSB treatment reversed the increase in LINC00612-induced 5-FU resistance. Mechanistically, LINC00612 specifically bound to miR-590-3p, which promoted 5-FU resistance in colon adenocarcinoma cells and attenuated the inhibitory effect of LINC00612 on GOLPH3 expression. CONCLUSION: PSB attenuates 5-FU chemoresistance in colon adenocarcinoma by regulating the LINC00612/miRNA-590-3p/GOLPH3 axis.
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GOLPH3 has been identified as an oncoprotein, playing a crucial role on progression and chemoresistancein of colon adenocarcinoma (COAD). However, it is still unclear the regulation of GOLPH3 expression at protein level. We discovered ubiquitin-specific proteases 6 (USP6) directly regulated the deubiquitination of the GOLPH3 protein and enhanced its stability in COAD. Overexpression of USP6 promoted COAD cell viability, inhibited apoptosis, and accelerated the growth of transplanted tumors growth in vitro and in vivo by deubiquitinating GOLPH3. Additionally, circCYFIP2 showed high expression levels in DDP-resistant colon cancer cells, promoting the cell proliferation. Mechanically, circCYFIP2 binds to both GOLPH3 protein and USP6, strengthening the interaction between GOLPH3 and USP6, and consequently induced DDP resistance in vitro and in vivo. In conclusion, USP6 operates as a deubiquitinase, targeting the GOLPH3 protein in COAD and enhancing its stability. Meanwhile, circCYFIP2 is crucial for the deubiquitination of GOLPH3 protein mediated by USP6 and acts as a scaffold to confer platinum resistance. The discovery of circCYFIP2/USP6/GOLPH3 pathway offers a potential target for overcoming chemoresistance in COAD.
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Neoplasias do Colo , Resistencia a Medicamentos Antineoplásicos , Proteínas de Membrana , Ubiquitina Tiolesterase , Ubiquitinação , Animais , Humanos , Masculino , Camundongos , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Cisplatino/farmacologia , Neoplasias do Colo/metabolismo , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Neoplasias do Colo/genética , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/fisiologia , Proteínas de Membrana/metabolismo , Proteínas de Membrana/genética , Camundongos Endogâmicos BALB C , Camundongos Nus , Ubiquitina Tiolesterase/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitinação/efeitos dos fármacosRESUMO
OBJECTIVE: In B-cell acute lymphoblastic leukemia (B-ALL), current intensive chemotherapies for adult patients fail to achieve durable responses in more than 50% of cases, underscoring the urgent need for new therapeutic regimens for this patient population. The present study aimed to determine whether HZX-02-059, a novel dual-target inhibitor targeting both phosphatidylinositol-3-phosphate 5-kinase (PIKfyve) and tubulin, is lethal to B-ALL cells and is a potential therapeutic for B-ALL patients. METHODS: Cell proliferation, vacuolization, apoptosis, cell cycle, and in-vivo tumor growth were evaluated. In addition, Genome-wide RNA-sequencing studies were conducted to elucidate the mechanisms of action underlying the anti-leukemia activity of HZX-02-059 in B-ALL. RESULTS: HZX-02-059 was found to inhibit cell proliferation, induce vacuolization, promote apoptosis, block the cell cycle, and reduce in-vivo tumor growth. Downregulation of the p53 pathway and suppression of the phosphoinositide 3-kinase (PI3K)/AKT pathway and the downstream transcription factors c-Myc and NF-κB were responsible for these observations. CONCLUSION: Overall, these findings suggest that HZX-02-059 is a promising agent for the treatment of B-ALL patients resistant to conventional therapies.
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Leucemia-Linfoma Linfoblástico de Células Precursoras , Tubulina (Proteína) , Humanos , Proliferação de Células , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Tubulina (Proteína)/metabolismo , Moduladores de Tubulina/farmacologia , Moduladores de Tubulina/uso terapêuticoRESUMO
Central lymph node metastasis (CLNM) of papillary thyroid carcinoma (PTC) is common. In our study, we built a nomogram to predict CLNM. We retrospectively analyzed 1,392 PTC patients. This group of patients was divided into a training cohort (including 1,009 patients) and a validation cohort (including 383 patients). Analyses of the correlation between inflammatory indicators, ultrasonic characteristics, pathological characteristics and CLNM were conducted. In the training cohort and validation cohort, the metastatic rates of CLNM were 60.16% and 64.23%, respectively. Univariate and multivariate logistic regression analyses demonstrated that Hashimoto's thyroiditis (HT), calcification, multifocality, capsule invasion, PLR (platelet-lymphocyte ratio) ≤ 130.34, large tumors and middle and lower positions were independent risk factors for CLNM. Then, we constructed a nomogram. The nomogram had good discrimination regardless of whether there was CLNM, with a C-index of 0.809. The calibration curve indicated that the nomogram had good visual and quantitative consistency (p = 0.213). Decision curve analysis showed that the nomogram improved the net clinical benefit with a threshold probability of 0-82% in the training cohort and 0-71% in the validation cohort. We constructed a nomogram to predict CLNM in PTC and assist surgeons in making personalized clinical decisions for PTC.
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INTRODUCTION: Thyroid carcinoma is the most frequent malignancy in different endocrine-related tumours. In this study, we demonstrated a long non-coding RNA LINC00092-associated molecular mechanism in promoting the progression of papillary thyroid carcinoma (PTC). MATERIAL AND METHODS: The expression of LINC00092 was analysed in the The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) patient cohorts and further determined by q-PCR. (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) (MTT) assay, and wound healing assay confirmed the function of LINC00092 in migration and proliferation. Q-ChIP validated the transcriptional target. Luciferase reporter assay validated the miRNA-mRNA target. RESULTS: The analysis in patient cohorts and in PTC TPC-1 cells showed that the expression of LINC00092 was repressed in thyroid carcinoma. In addition, the expression of LINC00092 was negatively associated with the advanced thyroid TNM stages. LINC00092 repressed epithelial-mesenchymal transition (EMT), migration, and proliferation of TPC-1 cells. Interestingly, we identified that MYB, a well-studied tumour promoter, is a transcription factor of LINC00092, thereby the expression of LINC00092 was directly repressed by MYB. Furthermore, miR-4741 was also validated as a direct target of MYB and was induced by MYB. Notably, LINC00092 was repressed by miR-4741 through the direct 3'-untranslational region (3'-UTR) target. Therefore, MYB induced EMT of TPC-1 cells by repressing LINC00092 directly or indirectly via miR-4741. CONCLUSIONS: Our study validated that LINC00092 is a tumour suppressor lncRNA in PTC. MYB directly or indirectly represses LINC00092, which contributes to the PTC progression. MYB, LINC00092, and miR-4741 form a coherent feed forward loop. The axis of MYB-LINC00092 promotes progression of PTC.
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MicroRNAs , Neoplasias da Glândula Tireoide , Humanos , Linhagem Celular Tumoral , Proliferação de Células , MicroRNAs/genética , MicroRNAs/metabolismo , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , RNA Longo não CodificanteRESUMO
BACKGROUND: The transcriptional repressor B-cell lymphoma 6 (BCL6) has been reported to inhibit inflammation. So far, experimental evidence for the role of BCL6 in bronchopulmonary dysplasia (BPD) is lacking. Our study investigated the roles of BCL6 in the progression of BPD and its downstream mechanisms. METHODS: Hyperoxia or lipopolysaccharide (LPS) was used to mimic the BPD mouse model. To investigate the effects of BCL6 on BPD, recombination adeno-associated virus serotype 9 expressing BCL6 (rAAV9-BCL6) and BCL6 inhibitor FX1 were administered in mice. The pulmonary pathological changes, inflammatory chemokines and NLRP3-related protein were observed. Meanwhile, BCL6 overexpression plasmid was used in human pulmonary microvascular endothelial cells (HPMECs). Cell proliferation, apoptosis, and NLRP3-related protein were detected. RESULTS: Either hyperoxia or LPS suppressed pulmonary BCL6 mRNA expression. rAAV9-BCL6 administration significantly inhibited hyperoxia-induced NLRP3 upregulation and inflammation, attenuated alveolar simplification and dysregulated angiogenesis in BPD mice, which were characterized by decreased mean linear intercept, increased radical alveolar count and alveoli numbers, and the upregulated CD31 expression. Meanwhile, BCL6 overexpression promoted proliferation and angiogenesis, inhibited apoptosis and inflammation in hyperoxia-stimulated HPMECs. Moreover, administration of BCL6 inhibitor FX1 arrested growth and development. FX1-treated BPD mice exhibited exacerbation of alveolar pathological changes and pulmonary vessel permeability, with upregulated mRNA levels of pro-inflammatory cytokines and pro-fibrogenic factors. Furthermore, both rAAV9-BCL6 and FX1 administration exerted a long-lasting effect on hyperoxia-induced lung injury (≥4 wk). CONCLUSIONS: BCL6 inhibits NLRP3-mediated inflammation, attenuates alveolar simplification and dysregulated pulmonary vessel development in hyperoxia-induced BPD mice. Hence, BCL6 may be a target in treating BPD and neonatal diseases.
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Displasia Broncopulmonar , Hiperóxia , Lesão Pulmonar , Animais , Humanos , Recém-Nascido , Camundongos , Animais Recém-Nascidos , Displasia Broncopulmonar/etiologia , Displasia Broncopulmonar/metabolismo , Modelos Animais de Doenças , Células Endoteliais/patologia , Hiperóxia/metabolismo , Inflamação/metabolismo , Lipopolissacarídeos/farmacologia , Pulmão/metabolismo , Lesão Pulmonar/tratamento farmacológico , Lesão Pulmonar/etiologia , Lesão Pulmonar/prevenção & controle , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteínas Proto-Oncogênicas c-bcl-6/metabolismo , RNA Mensageiro/metabolismoRESUMO
Background: The comparative advantages of robotic posterior retroperitoneal adrenalectomy (RPRA) over laparoscopic posterior retroperitoneal adrenalectomy (LPRA) remain a topic of ongoing debate within the medical community. This systematic literature review and meta-analysis aim to assess the safety and efficacy of RPRA compared to LPRA, with the ultimate goal of determining which procedure yields superior clinical outcomes. Methods: A systematic search was conducted on databases including PubMed, Embase, Web of Science, and the Cochrane Library database to identify relevant studies, encompassing both randomized controlled trials (RCTs) and non-RCTs, that compare the outcomes of RPRA and LPRA. The primary focus of this study was to evaluate perioperative surgical outcomes and complications. Review Manager 5.4 was used for this analysis. The study was registered with PROSPERO (ID: CRD42023453816). Results: A total of seven non-RCTs were identified and included in this study, encompassing a cohort of 675 patients. The findings indicate that RPRA exhibited superior performance compared to LPRA in terms of hospital stay (weighted mean difference [WMD] -0.78 days, 95% confidence interval [CI] -1.46 to -0.10; p = 0.02). However, there were no statistically significant differences observed between the two techniques in terms of operative time, blood loss, transfusion rates, conversion rates, major complications, and overall complications. Conclusion: RPRA is associated with a significantly shorter hospital stay compared to LPRA, while demonstrating comparable operative time, blood loss, conversion rate, and complication rate. However, it is important to note that further research of a more comprehensive and rigorous nature is necessary to validate these findings. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=453816, identifier CRD42023453816.
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Laparoscopia , Procedimentos Cirúrgicos Robóticos , Humanos , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Adrenalectomia/efeitos adversos , Adrenalectomia/métodos , Espaço Retroperitoneal/cirurgia , Perda Sanguínea CirúrgicaRESUMO
To compare perioperative outcomes between Holmium laser enucleation of the prostate (HoLEP) and robotic-assisted simple pasta-ectomy (RASP)for large-volume benign prostatic hyperplasia(> 80 ml). In August 2023, we undertook a comprehensive search of major global databases including PubMed, Embase, and Google Scholar, focusing solely on articles written in English. Studies that were merely reviews or protocols without any specific published data were omitted. Furthermore, articles that comprised conference abstracts or content not pertinent to our subject of study were also disregarded. To calculate the inverse variances and 95% confidence intervals (CIs) for categorical variables' mean differences, we employed the Cochran-Mantel-Haenszel approach along with random-effects models. The findings were denoted in the form of odds ratios (ORs) and 95% CIs. A p-value less than 0.05 was deemed to indicate statistical significance. Our finalized meta-analysis incorporated six articles, including one randomized controlled trial (RCT) and five cohort studies. These studies accounted for a total of 1218 patients, 944 of whom underwent Holmium Laser Enucleation of the Prostate (HoLEP) and 274 who underwent Robotic-Assisted Simple Prostatectomy (RASP). The pooled analysis from these six papers demonstrated that compared to RASP, HoLEP had a shorter hospital stay, shorter catheterization duration, and a lower blood transfusion rate. Moreover, HoLEP patients exhibited a smaller reduction in postoperative hemoglobin levels. Statistically, there were no significant differences between the two procedures regarding operative time, postoperative PSA, the weight of prostate specimens, IPSS, Qmax, PVR, QoL, and postoperative complications. (HoLEP) and (RASP) are both effective and safe procedures for treating large-volume benign prostatic hyperplasia. HoLEP, with its benefits of shorter catheterization and hospitalization duration, lesser decline in postoperative hemoglobin, and reduced blood transfusion needs, stands as a preferred choice for treating extensive prostate enlargement. However, further validation through more high-quality clinical randomized trials is required.
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Terapia a Laser , Lasers de Estado Sólido , Hiperplasia Prostática , Procedimentos Cirúrgicos Robóticos , Ressecção Transuretral da Próstata , Humanos , Masculino , Hemoglobinas , Terapia a Laser/efeitos adversos , Terapia a Laser/métodos , Lasers de Estado Sólido/efeitos adversos , Prostatectomia/efeitos adversos , Prostatectomia/métodos , Hiperplasia Prostática/cirurgia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Túlio/efeitos adversos , Ressecção Transuretral da Próstata/métodos , Resultado do TratamentoRESUMO
For papillary thyroid carcinoma (PTC) surgery requiring total thyroidectomy and central lymph node dissection, it is controversial whether the bilateral axillo-breast approach robotic thyroidectomy (BABA RT) can replace the open thyroidectomy (OT). To evaluate the efficacy of two surgical approaches. Relevant literatures were searched from PubMed, EMBASE and Cochrane Library. Studies comparing two surgical approaches and meeting the inclusion criteria were selected. Compared with OT, BABA RT showed a similar incidence of postoperative complications, including recurrent laryngeal nerve palsy, hypocalcemia, hypoparathyroidism, bleeding, chyle leakage and incision infection, as well as number of retrieved central lymph nodes and postoperative total dose of radioactive iodine. However, BABA RT involved longer operative time (weighted mean difference [WMD] 72.62, 95% confidence interval [CI] 48.15-97.10, P < .00001) and higher postoperative stimulated thyroglobulin level ([WMD] 0.12, 95% [CI] 0.05-0.19, P = .0006). The efficacy of BABA RT is basically similar to OT in this meta-analysis, but the higher postoperative stimulated thyroglobulin level attracts our attention. Longer operative time requires us to shorten. Randomized clinical trials with large samples and longer follow-up data are still essential to further demonstrate the value of the BABA RT.
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Procedimentos Cirúrgicos Robóticos , Neoplasias da Glândula Tireoide , Humanos , Câncer Papilífero da Tireoide/cirurgia , Tireoglobulina , Tireoidectomia/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Radioisótopos do Iodo , Axila/cirurgia , Resultado do Tratamento , Estudos RetrospectivosRESUMO
Background: The nerve-sparing (NS) effect of robot-assisted radical prostatectomy (RARP) on patients with a high-risk prostate cancer remains unclear. The objective of this study was to compare the urinary continence, erectile function and oncology outcomes of the nerve-sparing and non-nerve-sparing (NNS) group during RARP surgeries. Methods: We systematically searched databases including PubMed, Embase, Cochrane Library and Web of Science to identify relevant studies published in English up to December 2022. Newcastle-Ottawa Scale (NOS) was used as a quality evaluation tool to evaluate the quality of the literature parameters involved, including urinary continence, erectile function and oncologic outcomes, which were compared using the Stata 15.1 software (StataSE, USA). Results: A total of 8 cohort studies involving 2499 patients were included. A meta-analysis of results showed that the NS group was beneficial to the recovery of urinary continence (RR 0.46, 95%CI 0.22, 0.96; p=0.045<0.05) and erectile function (RR 0.32, 95%CI 0.16, 0.63; p=0.001<0.05) 12 months after surgeries, which showed a better oncological outcome (RR 1.31, 95%CI 1.01, 1.69; p=0.01<0.05). Conclusions: The current study results indicate that intraoperative NS during RARP is beneficial to long-term postoperative functional recovery and tumor prognosis of patients with high-risk prostate cancers. Due to interstudy interferences, the results should be interpreted with caution. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42022384647.
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OBJECTIVE: Parapharyngeal metastases (PPM) are rarely observed in patients with well-differentiated thyroid cancer (WDTC). Radioiodine (131 I) therapy has been the main treatment for metastatic and recurrent DTC after thyroidectomy. This study was performed to evaluate the clinicopathological features and long-term outcomes associated with survival of patients with PPM at the end of follow-up. DESIGN: In total, 14,984 consecutive patients with DTC who underwent 131 I therapy after total or near-total thyroidectomy from 2004 to 2021 were retrospectively reviewed. Therapeutic efficacy was evaluated using the Response Evaluation Criteria in Solid Tumours v1.1 and logistic regression analysis. The disease status was determined using dynamic risk stratification. Disease-specific survival (DSS) was assessed using the Kaplan-Meier method and a Cox proportional hazards model. PATIENTS: Seventy-five patients with PPM from WDTC were enroled in this study. Their median age at the initial diagnosis of PPM was 40.2 ± 14.1 years, and the patients comprised 32 men and 43 women (male:female ratio, 1.00:1.34). Of the 75 patients, 43 (57.33%) presented with combined distant metastases. Fifty-seven (76.00%) patients had 131 I avidity and 18 had non-131 I avidity. At the end of follow-up, 22 (29.33%) patients showed progressive disease. Sixteen of the 75 patients died; of the remaining 59 patients, 6 (8.00%) had an excellent response, 6 (8.00%) had an indeterminate response, 10 (13.33%) had an biochemical incomplete response, and 37 (49.33%) had a structural incomplete response. Multivariate analysis confirmed that age at initial PPM diagnosis, the maximal size of PPM, and 131 I avidity had significant effects on progressive disease of PPM lesions (p = .03, p= .02, and p < .01, respectively). The 5- and 10-year DSS rates were 98.49% and 62.10%, respectively. Age of ≥55 years at initial diagnosis of PPM and the presence of concomitant distant metastasis were independently associated with a poor prognosis (p = .03 and p = .04, respectively). CONCLUSION: The therapeutic effect for PPM was closely associated with 131 I avidity, age at initial PPM diagnosis, and maximal size of PPM at the end of follow-up. Age of ≥55 years at initial diagnosis of PPM and the presence of concomitant distant metastasis were independently associated with poor survival.
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Radioisótopos do Iodo , Neoplasias da Glândula Tireoide , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Prognóstico , Seguimentos , Radioisótopos do Iodo/uso terapêutico , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/patologia , TireoidectomiaRESUMO
Microplastics have been recognized as a widespread new pollutant in nature and have induced an increase in the occurrence of a variety of diseases in carp. An animal model of microplastic ingestion was successfully established in an aqueous environment. The gut microbiota was analysed using a metagenomic approach. The results showed a significant reduction in the relative abundances of Lactococcus garvieae, Bacteroides_paurosaccharolyticus, and Romboutsia_ilealis after PS-MPs treatment. The 16S Silva database was used to predict and analyse the known genes. Intestinal flora disorders related to infectious diseases, cancers, neurodegenerative diseases, endocrine and metabolic diseases, cardiovascular diseases, and other diseases were found. The intake of PS-MPs resulted in damage to carp intestinal tissue and apoptosis of intestinal epithelial cells. The levels of the inflammatory cytokines IL-1ß, IL-6, and TNF-α were significantly increased with the intake of PS-MPs. The gene and protein levels of GRP78, Caspase-3, Caspase-7, Caspase-9, Caspase-12, PERK, IRE1, and ATF6 were further examined in PS group. The occurrence of ERS and apoptosis in carp intestines was confirmed. These results suggest that the accumulation of PS-MPs in the aquatic environment can disturb the carp gut microbiota and induce ERS, apoptosis, and inflammation in the intestinal tissue.
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Carpas , Microbioma Gastrointestinal , Animais , Microplásticos/toxicidade , Poliestirenos , Plásticos , Intestinos , Inflamação/induzido quimicamente , Apoptose , Estresse do Retículo EndoplasmáticoRESUMO
PURPOSE: To evaluate whether the application of carbon nanoparticles (CNs) in total or near-total thyroidectomy combined with central lymph node dissection (CLND) for thyroid cancer (TC) is beneficial to lymph node dissection, parathyroid, and recurrent laryngeal nerve (RLN) protection. METHODS: Relevant literatures were systematically searched on PubMed, EMBASE, and Cochrane Library Databases until March 31, 2021. All analyses were performed using Revman Manager 5.3 software. The main results were the number of central lymph nodes, the number of central metastatic lymph nodes, accidental parathyroidectomy, postoperative hypoparathyroidism, postoperative hypocalcemia, and postoperative transient RLN paralysis. RESULTS: This meta-analysis identified 4 randomized controlled trials and 8 non-randomized controlled trials comprising 1870 patients. Compared with the control, the use of CNs was helpful to dissect more central lymph nodes (weighted mean difference [WMD]: 3.55, 95% confidence interval [CI]: 2.12-4.98, P < .00001) and central metastatic lymph nodes (WMD: 1.69, 95% CI:1.31-2.08, P < .00001), lower rate of accidental parathyroidectomy (odds ratio [OR]: .33, 95% CI: .23-.47, P < .00001), lower rate of both postoperative transient hypoparathyroidism (OR: .40, 95% CI: .31-.51, P < .00001), and transient hypocalcemia (OR: .37, 95% CI: .27-.51, P < .00001). However, there were no statistical difference between the groups for postoperative permanent hypoparathyroidism (OR: .29, 95% CI: .06-1.28, P = .10), postoperative permanent hypocalcemia (OR: .94, 95% CI: .10-9.16, P = .96), and postoperative transient RLN paralysis (OR: .66, 95% CI: .40-1.12, P = .12). CONCLUSIONS: The application of CNs in total or near-total thyroidectomy combined with CLND for TC can better dissect the central lymph nodes and protect parathyroid glands (PGs) and their function.
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Hipocalcemia , Hipoparatireoidismo , Nanopartículas , Neoplasias da Glândula Tireoide , Paralisia das Pregas Vocais , Humanos , Tireoidectomia/métodos , Hipocalcemia/etiologia , Hipocalcemia/prevenção & controle , Esvaziamento Cervical/métodos , Neoplasias da Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/patologia , Excisão de Linfonodo/métodos , Linfonodos/cirurgia , Linfonodos/patologia , Hipoparatireoidismo/etiologia , Hipoparatireoidismo/prevenção & controle , Hipoparatireoidismo/patologia , Carbono , Estudos RetrospectivosRESUMO
Organophosphate flame retardants (OPFRs) are alternatives to brominated flame retardants (BFRs) and have recently gained wide acceptance in various materials. For the treatment and prevention of diseases, it is also important to clarify the relationship between OPFRs and tumors, despite the fact that OPFRs are less toxic than BFRs. This research used the TCGA and CTD databases for transcriptome profiling and identifying OPFRs-related genes. GO and KEGG analyses suggested that OPFRs may be closely related to colorectal cancer (CRC), and genes correlated with OPFRs were significantly and differently expressed between tumor and normal group. Further, OPFRs-related genes were associated with a good prognosis in CRC patients. The deeper research demonstrated that one of the OPFRs-triphenyl phosphate could significantly increased the viability and proliferation of CRC cell lines compared with the control group. In addition, Our research also found that melatonin at 50 µM could significantly impact CRC cell proliferation and migration ability induced by TPP.
Assuntos
Neoplasias Colorretais , Retardadores de Chama , Linhagem Celular , Neoplasias Colorretais/genética , Retardadores de Chama/metabolismo , Retardadores de Chama/toxicidade , Humanos , Organofosfatos/metabolismo , Organofosfatos/toxicidade , Compostos Organofosforados/toxicidadeRESUMO
Arabidopsis (Arabidopsis thaliana) PROTEIN ARGININE METHYLTRANSFERASE5 (PRMT5), a highly conserved arginine (Arg) methyltransferase protein, regulates multiple aspects of the growth, development, and environmental stress responses by methylating Arg in histones and some mRNA splicing-related proteins in plants. Hydrogen sulfide (H2S) is a recently characterized gasotransmitter that also regulates various important physiological processes. l-cysteine desulfhydrase (LCD) is a key enzyme of endogenous H2S production. However, our understanding of the upstream regulatory mechanisms of endogenous H2S production is limited in plant cells. Here, we confirmed that AtPRMT5 increases the enzymatic activity of AtLCD through methylation modifications during stress responses. Both atprmt5 and atlcd mutants were sensitive to cadmium (Cd2+), whereas the overexpression (OE) of AtPRMT5 or AtLCD enhanced the Cd2+ tolerance of plants. AtPRMT5 methylated AtLCD at Arg-83, leading to a significant increase in AtLCD enzymatic activity. The Cd2+ sensitivity of atprmt5-2 atlcd double mutants was consistent with that of atlcd plants. When AtPRMT5 was overexpressed in the atlcd mutant, the Cd2+ tolerance of plants was significantly lower than that of AtPRMT5-OE plants in the wild-type background. These results were confirmed in pharmacological experiments. Thus, AtPRMT5 methylation of AtLCD increases its enzymatic activity, thereby strengthening the endogenous H2S signal and ultimately improving plant tolerance to Cd2+ stress. These findings provide further insights into the substrates of AtPRMT5 and increase our understanding of the regulatory mechanism upstream of H2S signals.
Assuntos
Proteínas de Arabidopsis , Arabidopsis , Sulfeto de Hidrogênio , Arabidopsis/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Metilação , Cistationina gama-Liase/genética , Sulfeto de Hidrogênio/farmacologia , Sulfeto de Hidrogênio/metabolismo , Arginina/metabolismoRESUMO
Background: Long noncoding RNAs (lncRNAs) have a vital function in tumor onset and progress. For instance, long intergenic noncoding RNA 00641 (LINC00641) has been linked to cancer modulation. Nonetheless, the precise biological roles of LINC00641 in colorectal cancer (CRC) remain elusive. Methods: The expression levels of LINC00641 as well as the docking sites for LINC00641 and miR-450b-5p were analyzed using public data resources and web-based analytic tools. The putative downstream targets of miR-450b-5p were also predicted. Next, we evaluated the biological functions and the contents of LINC00641 in CRC both in vivo and in vitro. We next explored the influence of LINC00641 on the growth, migration, and infiltration of CRC cells via cell proliferation, migration, and invasion experiments. Besides, qRT-PCR, western blotting, flow cytometry, luciferase enzyme reporter assay, and in vivo tumorigenicity assays were conducted. Results: Our results confirmed that LINC00641 was markedly upmodulated in CRC tissues and CRC cell lines, and the upmodulation was linked to poor survival. Notably, the proliferative and migratory abilities of HCT-116 and SW480 cells were significantly inhibited by the knockdown of LINC00641 both in vitro and in vivo, illustrating that LINC00641 exerted a tumor-promotion role in CRC. Mechanistically, LINC00641 could competitively bind miR-450b-5p, thereby expunging its inhibitory effect on GOLPH3 expression. Moreover, miR-450-5p and GOLPH3 were able to reverse LINC00641-mediated cellular processes. Conclusions: Overall, the findings of this study suggest that LINC00641 promotes the proliferative and migratory abilities of CRC through sponging the miR-450b-5p/GOLPH3 axis.
RESUMO
Multidrug-resistant (MDR) Staphylococcus aureus biofilms have emerged as a serious threat to human health. Recently, the development of antibiotic replacement therapy has gained much attention due to the potential application of bacteriocin. The present study sought to evaluate the antibacterial effect of bacteriocin XJS01 against MDR S. aureus, a previously reported bacteriocin against S. aureus strain 2612:1606BL1486 (S. aureus_26, an MDR strain demonstrated here), and its potential application as an antibiofilm agent. The minimum bactericide concentration of XJS01 against MDR S. aureus_26 was 33.18 µg/mL. XJS01 exhibited excellent storage stability and resistance against acid and reduced the density of established MDR S. aureus_26 biofilm. The hemolytic and HEK293T cytotoxicity activities of XJS01 and the histological analyses in mice confirmed its safety. Moreover, XJS01 effectively disrupted the MDR S. aureus_26 biofilm established on the skin wound surface and reduced the biofilm-isolated bacteria, thereby decreasing the release of pro-inflammatory cytokines and the proliferation of alternatively activated macrophages. Compared to mupirocin, XJS01 exhibited an excellent therapeutic effect on mice skin wounds, confirming it to be a potential alternative to antibiotics.