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INTRODUCTION: Choroidal neovascularization (CNV) is the feature of neovascular age-related macular degeneration (AMD). It has been demonstrated that inflammation plays a key role in the development of CNV. Here we aim to investigate how TLR9 agonist (CpG-ODN), one of the key regulators of inflammatory responses, suppresses CNV in vivo. MATERIALS AND METHODS: The cell viability was assessed by MTT and EdU test after CpG-ODN treatment. Endothelial cells gap assay, tube formation assay and transwell assay were practiced to observe how CpG-ODN affected the endothelial cells functions. The choroidal explants and laser-induced CNV model were built to investigate how CpG-ODN suppressed angiogenesis. The ERK and c-Jun expression were evaluated to assess if CpG-ODN affected cell proliferation. Flow cytometry and qPCR was practiced to observe how CpG-ODN regulated cell proliferation. RESULTS: Our data showed that CpG-ODN not only reduced CNV area in vivo, but also decreased the RPE damage. CpG-ODN inhibited endothelial cells from migration and forming tubes, while the effect was not toxic. EdU test and MTT test suggested that CpG-ODN inhibited endothelial cells proliferation. CpG-ODN significantly increased protein expression of phosphorylated c-Jun but reduced phosphorylated ERK in HUVECs, which was confirmed in ERK transfected 293T cells. JNK inhibitor abolished the suppression of endothelial cells migration and tube formation by CpG-ODN. The findings were also in agreement with the observation in CpG-ODN treated CNV eyes in vivo. The flow cytometry and qPCR data revealed that the suppression of cell motility by CpG-ODN was achieved by arresting endothelial cells cell cycle at G0/G1 phase. CONCLUSIONS: Our study demonstrated that CpG-ODN suppressed endothelial cell motility by restricting the cell cycle progression at G0/G1 phase, the effect of which was achieved by interacting with ERK/c-Jun pathways.
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Neovascularização de Coroide , Corioide/irrigação sanguínea , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/prevenção & controle , Células Endoteliais/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases , Receptor Toll-Like 9/metabolismoRESUMO
(1) Background: Colorectal cancer (CRC) is a common gastrointestinal malignancy, accounting for the second largest gastrointestinal tumor. MORC2, a newly discovered chromatin remodeling protein, plays an important role in the biological processes of various cancers. However, the potential mechanistic role of MORC2 in promoting proliferation of CRC carcinoma remains unclear. (2) Methods: The Cancer Genome Atlas database was analyzed using bioinformatics to obtain gene expression and clinical prognosis data. The cell proliferation was assessed by CCK8 and EdU assays, as well as xenograft. SA-beta-gal staining, Western blot, and ELISA assay were using to assess the cell senescence and potential mechanism. (3) Results: Our data showed that MORC2 expression was elevated in CRC patients. Depletion of MORC2 inhibited cellular proliferation both in vivo and in vitro. Further studies showed that the depletion of MORC2 enhanced p21 and p53 expression through decreasing HDAC4 and increasing pro-inflammatory factors IL-6 and IL-8, thus, promoting cellular senescence. (4) Conclusions: We concluded that increased MORC2 expression in CRC might play a critical role in tumorigenesis by regulating the cellular senescence, in addition, MORC2 could be a novel biomarker for clinical outcomes and prognosis and a treatment target for CRC.
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Interleucina-6 , Proteína Supressora de Tumor p53 , Linhagem Celular Tumoral , Proliferação de Células/genética , Senescência Celular/genética , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Humanos , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Proteínas Repressoras/metabolismo , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismoRESUMO
Diabetic retinopathy (DR) is one of the most severe clinical manifestations of diabetes mellitus and a major cause of blindness. DR is principally a microvascular disease, although the pathogenesis also involves metabolic reactive intermediates which induce neuronal and glial activation resulting in disruption of the neurovascular unit and regulation of the microvasculature. However, the impact of neural/glial activation in DR remains controversial, notwithstanding our understanding as to when neural/glial activation occurs in the course of disease. The objective of this study was to determine a potential protective role of neuropeptide Y (NPY) using an established model of DR permissive to N-methyl-D-aspartate (NMDA)-induced excitotoxic apoptosis of retinal ganglion cells (RGC) and vascular endothelial growth factor (VEGF)-induced vascular leakage. In vitro evaluation using primary retinal endothelial cells demonstrates that NPY promotes vascular integrity, demonstrated by maintained tight junction protein expression and reduced permeability in response to VEGF treatment. Furthermore, ex vivo assessment of retinal tissue explants shows that NPY can protect RGC from excitotoxic-induced apoptosis. In vivo clinical imaging and ex vivo tissue analysis in the diabetic model permitted assessment of NPY treatment in relation to neural and endothelial changes. The neuroprotective effects of NPY were confirmed by attenuating NMDA-induced retinal neural apoptosis and able to maintain inner retinal vascular integrity. These findings could have important clinical implications and offer novel therapeutic approaches for the treatment in the early stages of DR.
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Retinopatia Diabética/tratamento farmacológico , N-Metilaspartato/genética , Neuropeptídeo Y/farmacologia , Neovascularização Retiniana/tratamento farmacológico , Fator A de Crescimento do Endotélio Vascular/genética , Animais , Apoptose/efeitos dos fármacos , Microambiente Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Retinopatia Diabética/genética , Retinopatia Diabética/patologia , Células Endoteliais/efeitos dos fármacos , Humanos , Camundongos , N-Metilaspartato/farmacologia , Neuropeptídeo Y/genética , Ratos , Retina/efeitos dos fármacos , Retina/patologia , Células Ganglionares da Retina/efeitos dos fármacos , Células Ganglionares da Retina/patologia , Neovascularização Retiniana/genética , Neovascularização Retiniana/patologia , Fator A de Crescimento do Endotélio Vascular/farmacologiaRESUMO
OBJECTIVE: To investigate the influence of tumour location zone on positive surgical margin (PSM) status after Retzius-sparing robot-assisted radical prostatectomy (RS-RARP). MATERIALS AND METHODS: A total of 203 consecutive patients with prostate cancer (PCa) who underwent RS-RARP at our centre were divided into three cohorts according to the tumour zonal origin described on preoperative magnetic resonance imaging (MRI). Clinical and pathological characteristics were compared among the three groups. The associations of clinicopathological variables with PSM status after RS-RARP were also evaluated. RESULTS: The rates of PSM in patients with transition zone (TZ) and mixed origin tumours were significantly higher than in patients with peripheral zone tumours (P < 0.01). Of the PSMs in patients with TZ and mixed origin cancers, 42.0% and 40.9%, respectively, were located at the anterior part of the gland. On multivariate analysis, presence of a TZ tumour was significantly associated with a higher PSM rate after RS-RARP (P < 0.01). Sub-analysis showed that high-risk patients with TZ tumours had a higher risk of PSM after RS-RARP (P < 0.01). CONCLUSION: Presence of a TZ tumour is an independent risk factor for PSMs after RS-RARP. Preoperative identification of TZ tumours might aid surgical planning for the Retzius-sparing technique, especially in high-risk patients.
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Imageamento por Ressonância Magnética/métodos , Margens de Excisão , Estadiamento de Neoplasias/métodos , Cuidados Pré-Operatórios/métodos , Próstata/patologia , Prostatectomia/métodos , Procedimentos Cirúrgicos Robóticos/métodos , Idoso , Idoso de 80 Anos ou mais , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Próstata/cirurgia , Estudos Retrospectivos , Fatores de RiscoRESUMO
OBJECTIVE: To evaluate the impact of Retzius-sparing robot-assisted radical prostatectomy (posterior approach) on early recovery of urinary continence (UC) compared to the conventional approach (anterior approach) for the treatment of clinically localized prostate cancer (PCa). METHODS: A total of 110 consecutive patients with clinically localized PCa were prospectively randomized in a 1:1 ratio to an anterior group (n = 55) or a posterior group (n = 55). The primary outcome was immediate UC, defined as freedom from any pad use within 1 week after removal of the urinary catheter. The UC rate following surgery was also calculated with Kaplan-Meier curves, and the log-rank test was used for statistical comparison. Intra-operative outcomes, pathological data and oncological outcomes, including positive surgical margin (PSM) status and biochemical recurrence-free survival (BCRFS), were also compared between the two groups. The comparison of the two approaches was also analysed in subgroups after risk stratification. RESULTS: Of the patients who underwent the posterior approach, 69.1% achieved immediate UC compared with 30.9% in the anterior group (relative risk 2.24, 95% confidence interval [CI] 1.48-3.51; P = 0.000). The relative Kaplan-Meier curves for UC during the 12-month follow-up revealed statistically better recovery in the posterior group when compared with the anterior group (hazard ratio [HR] 1.51, 95% CI 1.01-2.24; log-rank P = 0.007). No statistically significant differences were observed between the groups regarding complications (P = 0.399), PSM status (P = 0.225) or BCRFS (HR 4.80, 95% CI 0.97-23.78; log-rank P = 0.111). In sub-analyses, no significant difference between the two approaches with regard to UC recovery in patients with high-risk PCa was observed (HR 1.26, 95% CI 0.63-2.51; log-rank P = 0.415). CONCLUSIONS: The Retzius-sparing approach significantly improved early recovery of UC compared to the conventional approach. Further prospective studies are needed to confirm the benefits of the Retzius-sparing approach for clinically localized PCa, especially for high-risk cases.
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Tratamentos com Preservação do Órgão/métodos , Complicações Pós-Operatórias/epidemiologia , Prostatectomia/métodos , Procedimentos Cirúrgicos Robóticos , Incontinência Urinária/epidemiologia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Tratamentos com Preservação do Órgão/efeitos adversos , Estudos Prospectivos , Próstata/cirurgia , Prostatectomia/efeitos adversos , Neoplasias da Próstata/cirurgia , Procedimentos Cirúrgicos Robóticos/efeitos adversos , Procedimentos Cirúrgicos Robóticos/métodosRESUMO
Somatostatin, a naturally produced neuroprotective peptide, depresses excitatory neurotransmission and exerts anti-proliferative and anti-inflammatory effects on the retina. In this review, we summarize the progress of somatostatin treatment of diabetic retinopathy through analysis of relevant studies published from February 2019 to February 2023 extracted from the PubMed and Google Scholar databases. Insufficient neuroprotection, which occurs as a consequence of declined expression or dysregulation of retinal somatostatin in the very early stages of diabetic retinopathy, triggers retinal neurovascular unit impairment and microvascular damage. Somatostatin replacement is a promising treatment for retinal neurodegeneration in diabetic retinopathy. Numerous pre-clinical and clinical trials of somatostatin analog treatment for early diabetic retinopathy have been initiated. In one such trial (EUROCONDOR), topical administration of somatostatin was found to exert neuroprotective effects in patients with pre-existing retinal neurodysfunction, but had no impact on the onset of diabetic retinopathy. Overall, we concluded that somatostatin restoration may be especially beneficial for the growing population of patients with early-stage retinopathy. In order to achieve early prevention of diabetic retinopathy initiation, and thereby salvage visual function before the appearance of moderate non-proliferative diabetic retinopathy, several issues need to be addressed. These include the needs to: a) update and standardize the retinal screening scheme to incorporate the detection of early neurodegeneration, b) identify patient subgroups who would benefit from somatostatin analog supplementation, c) elucidate the interactions of somatostatin, particularly exogenously-delivered somatostatin analogs, with other retinal peptides in the context of hyperglycemia, and d) design safe, feasible, low cost, and effective administration routes.
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Inflammation plays a key role in the progression of choroidal neovascularization (CNV). Regular intravitreal injection of anti-VEGF medication is required for many patients to sustain eye condition as CNV always recurs due to persistent chronic inflammation in the retina and choroid. Marine bromophenols (BDB) have been widely studied due to their diverse bioactivities, including anti-inflammatory effect, though the mechanism of which remained unclear. Our study demonstrated that BDB could restricted endothelial cells' function and suppressed choroidal explants both in vitro and in vivo without out affecting the cells viability. BDB also significantly reduced numerous inflammatory cytokines in both raw cells and choroidal tissue, including IL-1ß, IL-6, TNF-α, IL-4 and MMP-9. Moreover, we demonstrated that BDB down regulated phosphorylation of NF-κB p65 in the raw cells. By Co-IP assay, HUWE1 was found to be bound with BDB and the binding location was at sequences position 4214. When overexpressed HUWE1 in HUVECs, the suppression of endothelial cells' function by BDB became more significant. Taken together, the findings in this study showed that BDB suppressed endothelial cells' function and choroidal neovascularization by targeting HUWE1 through NF-κB pathway, which suggested that BDB could be a potential therapeutic candidate in treating chronic inflammation in choroidal neovascularization.
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Benzidinas , Neovascularização de Coroide , NF-kappa B , Humanos , Animais , Camundongos , NF-kappa B/metabolismo , Células Endoteliais/metabolismo , Transdução de Sinais , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/metabolismo , Inflamação/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Objective: Choroidal neovascularization (CNV) represents the predominant form of advanced wet Age-related Macular Degeneration (wAMD). Macrophages play a pivotal role in the pathological progression of CNV. Meteorin-like (Metrnl), a novel cytokine known for its anti-inflammatory properties in macrophages, is the focus of our investigation into its mechanism of action and its potential to impede CNV progression. Methods: Cell viability was evaluated through CCK-8 and EdU assays following Metrnl treatment. Expression levels of inflammatory cytokines and proteins were assessed using quantitative reverse-transcription polymerase chain reaction(qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and western blot techniques. Protein-protein interactions were identified through protein mass spectrometry and co-immunoprecipitation (Co-IP). Additionally, in vivo and in vitro neovascularization models were employed to evaluate angiogenesis. Results: Our results revealed downregulated Metrnl levels in the choroid-sclera complex of CNV mice, the aqueous humor of wAMD patients, and activated macrophages. Metrnl overexpression demonstrated a reduction in pro-inflammatory cytokine production, influenced endothelial cell function, and suppressed angiogenesis in choroid explants and CNV models. Through protein mass spectrometry and Co-IP, we confirmed Metrnl binds to UCHL-1 to modulate the NF-κB signaling pathway. This interaction inhibited the transcription and expression of pro-inflammatory cytokines, ultimately suppressing angiogenesis. Conclusion: In summary, our findings indicate that Metrnl down-regulates macrophage pro-inflammatory cytokine secretion via the UCHL-1/NF-κB signaling pathway. This mechanism alleviates the inflammatory microenvironment and effectively inhibits choroidal neovascularization.
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Neovascularização de Coroide , NF-kappa B , Transdução de Sinais , Neovascularização de Coroide/metabolismo , Neovascularização de Coroide/patologia , Neovascularização de Coroide/genética , Animais , Camundongos , Humanos , NF-kappa B/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Macrófagos/metabolismo , Macrófagos/imunologia , Corioide/metabolismo , Corioide/patologia , Corioide/irrigação sanguínea , Masculino , Degeneração Macular Exsudativa/metabolismo , Degeneração Macular Exsudativa/genética , Degeneração Macular Exsudativa/patologia , Inflamação/metabolismo , Citocinas/metabolismoRESUMO
Colorectal cancer (CRC) is the third leading cancer type worldwide and accounts for the second highest rate of cancer-related mortality. Liver metastasis significantly contributes to the mortality associated with CRC, but the fundamental mechanisms behind it remain unclear. Signal-induced proliferation-associated protein 1 (SIPA1), a GTPase activating protein, has been shown to promote metastasis in breast cancer. In this study, our objective was to explore the role of SIPA1 in regulating epithelial-mesenchymal transition (EMT) in CRC. The analysis of The Cancer Genome Atlas (TCGA) database revealed that the expression level of SIPA1 mRNA was notably upregulated and exhibited a positively correlated with EMT and STAT3 signaling pathways in CRC. Knockdown of SIPA1 impairs CRC cell proliferation and migration. Further studies on the reliance of SIPA1 on STAT3 signaling for EMT regulation have shown that SIPA1 stimulates the activation of STAT3, resulting in its nuclear translocation. The co-treatment of overexpressed SIPA1 with the STAT3 inhibitor STTITA has shown that SIPA1 regulates the expression of EMT-related markers through STAT3. Our study indicate that SIPA1 promotes CRC metastasis by activating the STAT3 signaling pathway, underscoring the potential of SIPA1 as a therapeutic target for metastatic CRC patients.
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OBJECTIVE: Kidney renal clear cell carcinoma (KIRC) is a common renal malignancy that has a poor prognosis. As a member of the F box family, cyclin F (CCNF) plays an important regulatory role in normal tissues and tumors. However, the underlying mechanism by which CCNF promotes KIRC proliferation still remains unclear. METHODS: Bioinformatics methods were used to analyze The Cancer Genome Atlas (TCGA) database to obtain gene expression and clinical prognosis data. The CCK8 assay, EdU assay, and xenograft assay were used to detect cell proliferation. The cell senescence and potential mechanism were assessed by SA-ß-gal staining, Western blotting, as well as ELISA. RESULTS: Our data showed that CCNF was highly expressed in KIRC patients. Meanwhile, downregulation of CCNF inhibited cell proliferation in vivo and in vitro. Further studies showed that the reduction of CCNF promoted cell senescence by decreasing cyclin-dependent kinase 1 (CDK1), increasing the proinflammatory factors interleukin (IL)-6 and IL-8, and then enhancing the expression of p21 and p53. CONCLUSION: We propose that the high expression of CCNF in KIRC may play a key role in tumorigenesis by regulating cell senescence. Therefore, CCNF shows promise as a new biomarker to predict the clinical prognosis of KIRC patients and as an effective therapeutic target.
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Carcinoma de Células Renais , Senescência Celular , Ciclinas , Neoplasias Renais , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Proteína Quinase CDC2 , Pontos de Checagem do Ciclo Celular , Senescência Celular/genética , Ciclinas/genética , Ciclinas/metabolismo , Neoplasias Renais/diagnósticoRESUMO
Arsenic trioxide has been reported to inhibit cell growth and induce apoptotic cell death in many human cancer cells including breast cancer. However, the precise molecular mechanisms underlying the anti-tumor activity of arsenic trioxide are still largely unknown. In the present study, we assessed the effects of arsenic trioxide on cell viability and apoptosis in breast cancer cells. For mechanistic studies, we used multiple cellular and molecular approaches such as MTT assay, apoptosis ELISA assay, gene transfection, RT-PCR, Western blotting, and invasion assays. For the first time, we found a significant reduction in cell viability in arsenic trioxide-treated cells in a dose-dependent manner, which was consistent with induction of apoptosis and also associated with down-regulation of Notch-1 and its target genes. Taken together, our findings provide evidence showing that the down-regulation of Notch-1 by arsenic trioxide could be an effective approach, to cause down-regulation of Bcl-2, and NF-κB, resulting in the inhibition of cell growth and invasion as well as induction of apoptosis. These results suggest that the anti-tumor activity of arsenic trioxide is in part mediated through a novel mechanism involving inactivation of Notch-1 and its target genes. We also suggest that arsenic trioxide could be further developed as a potential therapeutic agent for the treatment of breast cancer.
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Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Arsenicais/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Óxidos/farmacologia , Receptores Notch/antagonistas & inibidores , Trióxido de Arsênio , Western Blotting , Neoplasias da Mama/metabolismo , Movimento Celular/efeitos dos fármacos , Feminino , Humanos , NF-kappa B/genética , NF-kappa B/metabolismo , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Receptores Notch/genética , Receptores Notch/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais , Células Tumorais CultivadasRESUMO
OBJECTIVE: To study the effects of arsenic trioxide (As2O3) on the proliferation and the migration force of human breast cancer SKBR-3 cell and the expression of Notch1. METHODS: SKBR-3 cells were cultured with different concentrations of As2O3 for 24 h and with the final concentration of 8 micromol/L for 24, 48, and 72 h. The effects of As2O3 on the cell proliferation of SKBR-3 were detected by MTT assay. The effects of the migration force of SKBR-3 cells were detected by Transwell. The expression of Notch1 mRNA was detected using reverse transcription polymerase chain reaction (RT-PCR). The expression of Notch1 protein was detected using Western blot. RESULTS: As2O3 could significantly inhibit the proliferation of SKBR-3 cells in a concentration- and time-dependent manner (P < 0.05). It also could inhibit the migration force of SKBR-3 cells (P < 0.05). Results of RT-PCR and Western blot showed that Notch1 mRNA and protein levels obviously decreased (P < 0.05). CONCLUSION: As2O3 could inhibit the expression of Notch1 and the cell proliferation and the migration force of SKBR-3 cells, which primarily revealed that As2O3 might affect the biological behavior of human breast cancer cells possibly through Notch1 signaling pathway, thus providing theoretical and experimental bases for treating breast cancer by arsenic.
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Arsenicais/farmacologia , Neoplasias da Mama/metabolismo , Proliferação de Células/efeitos dos fármacos , Óxidos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Trióxido de Arsênio , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Feminino , Humanos , RNA Mensageiro/genética , Receptor Notch1/metabolismoRESUMO
Retinal degeneration is a debilitating ocular complication characterized by the progressive loss of photoreceptors and other retinal neurons, which are caused by a group of retinal diseases affecting various age groups, and increasingly prevalent in the elderly. Age-related macular degeneration, diabetic retinopathy and glaucoma are among the most common complex degenerative retinal disorders, posing significant public health problems worldwide largely due to the aging society and the lack of effective therapeutics. Whilst pathoetiologies vary, if left untreated, loss of retinal neurons can result in an acquired degeneration and ultimately severe visual impairment. Irrespective of underlined etiology, loss of neurons and supporting cells including retinal pigment epithelium, microvascular endothelium, and glia, converges as the common endpoint of retinal degeneration and therefore discovery or repurposing of therapies to protect retinal neurons directly or indirectly are under intensive investigation. This review overviews recent developments of potential neuroprotectants including neuropeptides, exosomes, mitochondrial-derived peptides, complement inhibitors, senolytics, autophagy enhancers and antioxidants either still experimentally or in clinical trials. Effective treatments that possess direct or indirect neuroprotective properties would significantly lift the burden of visual handicap.
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An accessory spleen refers to single or multiple splenic tissues that appear outside the normal spleen position and have structures and functions similar to those of a normal spleen. We herein present a rare case of a 31-year-old woman who was hospitalized because of a 14-year history of sudden left upper abdominal pain after running. Abdominal computed tomography suggested a large soft tissue mass at the left renal hilum surrounded by several enlarged lymph nodes, which was totally different from computed tomography scanning of normal accessory spleen. The mass was resected by robot-assisted laparoscopic surgery. Histopathological examination confirmed the diagnosis of accessory spleen. The incidence of retroperitoneal accessory spleen is very rare, which should be differentiated with retroperitoneal tumors.
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Anormalidades do Sistema Digestório , Neoplasias Retroperitoneais , Adulto , Feminino , Humanos , Espaço Retroperitoneal/diagnóstico por imagem , Espaço Retroperitoneal/cirurgia , Baço/diagnóstico por imagem , Baço/cirurgia , Tomografia Computadorizada por Raios XRESUMO
Myostatin (MSTN) is a member of the transforming growth factor beta superfamily and is a negative regulator of myogenesis. It has been shown to function by controlling the proliferation of myoblasts. MSTN inhibition is considered as a promising treatment for promoting animal growth in livestock. Nanobodies, a special antibody discovered in camel, have arisen as an alternative to conventional antibodies and have shown great potential when used as tools in different biotechnology fields, such as diagnostics and therapy. In this study, we examined the effect of MSTN inhibition by RMN on the muscle growth of mice. The results showed that RMN could specifically detect and bind MSTN, as well as inhibit MSTN activity. A significant increase in skeletal muscle mass was observed after intramuscular injection of RMN into mice. Enhanced muscle growth occurred because of myofiber hypertrophy. These results offer a promising approach to enhance muscle growth that warrants further investigation in domestic animals.
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Bladder cancer (BC) brings a heavy burden to afflicted patients worldwide. In order to find new diagnostic markers and therapeutic targets for this disease, we investigated the role of a novel lncRNA, AC114812.8, in bladder cancer progression. Clone formation and CCK-8 assays were used to detect the proliferative capacity of the cells, and the transwell assay was used to explore their invasion and migration abilities. Wound healing experiments were also used to detect cell migration. Luciferase reporter assays were used to investigate the interactions between lncRNA, target gene and miRNA. The expression of FUT4 and marker genes related to epithelial-mesenchymal transition was explored through western blot analysis. Our findings revealed that AC114812.8 was significantly upregulated in BC and could markedly facilitate the proliferation, migration, and invasion of bladder cancer cells both in vitro and in vivo. Furthermore, duel-luciferase reporter assay revealed that AC114812.8 could regulate the FUT4 expression level by sponging miR-371b-5p to facilitate BC progression. We detected the levels of EMT-related biomarkers in AC114812.8-overexpressing BC cells by western blot analysis and found that AC114812.8 could promote EMT process. Rescue experiments showed that miR-371b-5p could rescue the effect of AC114812.8 on proliferation and metastasis of BC. Our results suggest that AC114812.8 could be a novel prognostic biomarker and therapeutic target for bladder cancer.
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Progressão da Doença , Fucosiltransferases/biossíntese , MicroRNAs/biossíntese , RNA Longo não Codificante/biossíntese , Neoplasias da Bexiga Urinária/metabolismo , Animais , Linhagem Celular Transformada , Linhagem Celular Tumoral , Fucosiltransferases/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , RNA Longo não Codificante/genética , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Ensaios Antitumorais Modelo de Xenoenxerto/métodosRESUMO
BACKGROUND: Studies regarding predictive factors of urinary continence following Retzius-sparing radical prostatectomy (RP) is limited. This study was designed to evaluate association of urethral parameters on preoperative magnetic resonance imaging (MRI) and immediate recovery of urinary continence following Retzius-sparing robot assisted radical prostatectomy (RS-RARP). METHODS: This retrospective cohort study enrolled 156 patients with clinically localized prostate cancer who underwent MRI before RS-RARP. We measured the following structures on preoperative MRI: minimal residual membranous urethral length (mRUL), peri-urethral sphincter complex (PSC) thickness, urethral wall thickness (UWT), the thicknesses of the levator ani muscle (LAM) and obturator internus muscle (OIM). Immediate urinary continence was defined as patients reported freedom from using safety pad within 7 days after removal of urinary catheter. Patients were divided into two groups according the median of each parameter on MRI. We retrospectively analyzed the patients in term of preoperative clinical factors and postoperative urinary continence. RESULTS: A total of 100 patients (64.1%) reported immediate urinary continence after RS-RARP. Immediate urinary continence was significantly more in patients with longer mRUL (≥8.70 mm) than in patients with shorter mRUL (<8.70 mm; P=0.000). On multivariable analysis, longer mRUL was significantly related to immediate urinary continence after RS-RAPA (odds ratio 8.265; P=0.000). PSC, UWT, LAM and OIM were not associated with immediate urinary continence. CONCLUSIONS: Our results firstly demonstrated that preoperative mRUL measured on MRI was an independent predictor of immediate urinary continence following RS-RARP. Therefore, preservation of membranous urethra is still the anatomical basis of better urinary outcome after RS-RARP.
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BACKGROUND: Peptide drugs provide promising regimes in bladder cancer. In order to identify potential bioactive peptides involved in bladder cancer, we performed the present study. METHODS: Liquid chromatography/mass spectrometry assay was used to compare the endogenous peptides between bladder cancer and normal control. The potential biological functions of these dysregulated peptides are assessed by GO analysis and KEGG pathway analysis of their precursors. The SMART and UniProt databases are used to identify the sequences of the dysregulated peptides located in the functional domains. The Open Targets Platform database was used to investigate the precursors related to metabolic diseases. RESULTS: A total of 9 up-regulated peptides and 110 down-regulated peptides in bladder cancer compared with normal control were identified (fold change > 1.2, P < 0.05). The MW of these dysregulated peptides ranged from 500 Da to 2500 Da and the MW of all identified peptides was below 3500 Da. The GO and KEGG pathway analysis indicated that these dysregulated peptides could play an important role in bladder cancer. Our further analysis revealed that 45HFNPRFNAHGDAN 57 derived from LGALS1 and those peptides derived from P4HB and SERPINA1 might be the promising diagnostic biomarkers and therapeutic targets of bladder cancer. CONCLUSION: In the present study, we have identified the profile of the peptides significantly dysregulated in bladder cancer. Moreover, using bioinformatic analysis, we found the peptides derived from LGALS1, P4HB and SERPINA1 could be the promising diagnostic biomarkers and therapeutic targets of bladder cancer.
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Type 2 papillary renal cell carcinoma (PRCC) is a malignant tumor originated from renal tubular epithelial cells. Here we present a rare case of extrarenal type 2 PRCC which is located at the right lateral side of the retroperitoneal inferior vena cava. No suspicious lesions were detected in the bilateral kidneys. The diagnosis was confirmed by histopathological examination after complete excision of the tumor. No recurrence was observed in 5 months of follow-up after surgery.
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Bladder cancer (BC) is one of the most common malignant tumors in males globally. Its progression imposes a heavy burden on patients; however, the expression profile of circular (circ)RNAs in BC progression remains unclear. This study explored changes in circRNA expression during BC progression by sequencing different grade BC samples and normal controls to reveal the circRNA expression profiles of different BC grades. Gene Ontology (GO) and Kyoto Encyclopedia of Gens and Genomes (KEGG) pathway analyses, and proteinprotein interaction network construction were used to predict pathways that the differentially expressed circRNAs may participate in. circRNA expression levels were detected using reverse transcriptionquantitative polymerase chain reaction (RTqPCR) and dualluciferase reporter assays were used to investigate the interactions between circRNA and microRNA (miR). Cell Counting Kit8 and Transwell assays were also performed to detect cell proliferation, migration, and invasion. In total, 244 circRNAs were found to be differentially expressed in highgrade BC compared to lowgrade BC, whilst 316 dysregulated circRNAs were detected in highgrade BC compared with normal urothelium. Furthermore, 42 circRNAs overlapped between the two groups, seven of which were randomly selected and detected by RTqPCR to validate the sequencing results. GO analysis and KEGG pathway analyses revealed that the differentially expressed circRNAs may participate in BC via 'GTPase activity regulation', 'cell junction', and 'focal adhesion' pathways. Of note, we proposed that a novel circRNA in BC progression, hsa_circ_0137606, could suppress BC proliferation and metastasis by sponging miR1231. Through bioinformatics analysis, we predicted that PH domain and leucine rich repeat protein phosphatase 2 could be a target of the hsa_circ_0137606/miR1231 axis in BC progression. Using highthroughput sequencing, this study revealed the circRNA expression profiles of different grades of BC and proposed that the novel circRNA, hsa_circ_0137606, suppresses BC proliferation and metastasis by sponging miR1231. Our findings may provide novel insight into potential therapeutic targets for treating BC.