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The lacrimal gland is responsible for maintaining the health of the ocular surface through the production of tears. However, our understanding of the immune system within the lacrimal gland is currently limited. Therefore, in this study, we utilized single-cell RNA sequencing and bioinformatic analysis to identify and analyze immune cells and molecules present in the lacrimal glands of normal mice. A total of 34,891 cells were obtained from the lacrimal glands of mice and classified into 18 distinct cell clusters using Seurat clustering. Within these cell populations, 26 different immune cell subpopulations were identified, including T cells, innate lymphocytes, macrophages, mast cells, dendritic cells, and B cells. Network analysis revealed complex cell-cell interactions between these immune cells, with particularly significant interactions observed among T cells, macrophages, plasma cells, and dendritic cells. Interestingly, T cells were found to be the main source of ligands for the Thy1 signaling pathway, while M2 macrophages were identified as the primary target of this pathway. Moreover, some of these immune cells were validated using immunohistological techniques. Collectively, these findings highlight the abundance and interactions of immune cells and provide valuable insights into the complexity of the lacrimal gland immune system and its relevance to associated diseases.
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Aparelho Lacrimal , Aparelho Lacrimal/patologia , Lágrimas/metabolismo , Linfócitos T , Linfócitos , RNA/metabolismoRESUMO
PURPOSE: To determine age-and sex-related changes in periocular morphology in Caucasians using a standardized protocol. METHODS: Healthy Caucasian volunteers aged 18-35 and 60-90 years old were recruited from the Department of Ophthalmology, Faculty of Medicine and University Hospital, Cologne, between October 2018 and May 2020. Volunteers with facial asymmetry, facial deformities, history of facial trauma, facial surgery, botox injection, eyelid ptosis, strabismus, or nystagmus, were excluded. Standardized three-dimensional facial photos of 68 young volunteers and 73 old volunteers were taken in this clinical practice. Position changes of endocanthion, pupil center, and exocanthion were analyzed in different age and gender groups, including palpebral fissure width (PFW): distance between endocanthions (En-En), pupil centers (Pu-Pu), exocanthions (Ex-Ex), endocanthion and nasion (En-Na), pupil center and nasion (Pu-Na), exocanthion and nasion (Ex-Na), endocanthion and pupil center (Pu-En), exocanthion and pupil center (Pu-Ex), and palpebral fissure inclination (PFI); angle of endocanthions to nasion (En-Na-En), pupils to nasion (Pu-Na-Pu), exocanthions to nasion (Ex-Na-Ex); endocanthion inclination (EnI), and exocanthion inclination (ExI). RESULTS: PFW, En-En, Ex-Na, Pu-Ex, PFI, ExI, and Ex-Na-Ex were significantly different between the young and old groups (p ≤ 0.004). There were sex-related differences in PFW, Ex-Ex, En-Na, Pu-Na, Ex-Na, Pu-En, PFI, and EnI between both groups (p ≤ 0.041). CONCLUSION: The position change of the pupil is minimal relative to age; it is preferred to establish the reference plane to describe periocular changes. The endocanthion tends to move temporally and inferiorly, while the exocanthion tends to shift nasally and inferiorly with age.
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Blefaroptose , Estrabismo , Humanos , Antropometria , Pálpebras/anatomia & histologia , PupilaRESUMO
Graves ophthalmopathy (GO), which occurs in autoimmune thyroid disease, can reduce patients' quality of life due to its impact on visual function, physical appearance, and emotional health. Corticosteroids have been the first-line treatment for GO. More recently, the pathogenesis of GO has made significant progress. Various targeting biological agents and immunosuppressive agents make GO management more promising. Fully understanding GO pathogenesis and precise clinical management are beneficial for the prognosis of patients. Therefore, we conducted a comprehensive review of the medical management of GO and summarized research developments to highlight future research issues.
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Oftalmopatia de Graves , Humanos , Oftalmopatia de Graves/diagnóstico , Oftalmopatia de Graves/tratamento farmacológico , Qualidade de Vida , Imunossupressores/uso terapêuticoRESUMO
BACKGROUND: To explore the research trends for uveal melanoma with bibliometric methods using Web of Science Core Collection (WoSCC) and PubMed (PM). METHODS: To find UM-related studies, "uveal melanoma" was used as search term in the WoSCC and PM for the period time from 2000 to 2020. Bibliographic coupling analysis was used to investigate the journals with the highest number of UM-related publications. VOSviewer (VV) was used for mapping the knowledge domain and visualizing the co-occurrence of terms, authors, organizations, countries, co-citation literature, and keywords. The knowledge map based on WoSCC and PM was compared. RESULTS: In the WoSCC 3,748 articles were found, while in PM the search resulted in 3,403 articles. The number of original articles has steadily grown in general in the past two decades. The top ten authors were contributing to 23% (n = 856) of all publications, while the top 10 institutions published 41% (n = 1524) of all articles. The top 3 journals with the highest number of publications for UM-related research included Investigative ophthalmology & visual science, Ophthalmology, and British Journal of Ophthalmology. Co-occurrence analysis based on author keywords showed 6 clusters. The most frequent keywords included are metastasis, prognosis, and brachytherapy. The latest research hotspots focused on BAP1, immunotherapy and GNAQ. CONCLUSIONS: Genetics and immunology are the latest research frontiers in uveal melanoma. There is a clear need for interdisciplinary, molecular and clinical research approaches to improve the fatal prognosis of uveal melanoma patients.
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Melanoma , Neoplasias Uveais , Bibliometria , Humanos , Melanoma/terapia , Publicações , Neoplasias Uveais/terapiaRESUMO
Recent studies indicate mammalian target of rapamycin (mTOR) may play an important role in PCa progression and drug resistance. Here, we investigated the effects of a novel mTORC1/C2 dual inhibitor, AZD2014, on naive and docetaxel (Doc)-pre-treated castration-resistant PCa (CRPC) cells and explored its therapeutic potential in CRPCs. In the current study, AZD2014 has a greater inhibitory effect against 4EBP1 and AKT phosphorylation than rapamycin in CRPC cells and prevented the feedback activation of AKT signalling. Importantly, AZD2014 suppressed CRPC cell growth in vitro by suppressing proliferation, apoptosis, cell cycle arrest at G1 phase and autophagy to a greater extent than rapamycin. Moreover, AZD2014 was more efficacious than rapamycin in inhibiting migration, invasion and EMT progression in Doc-sensitive and Doc-resistant CRPC cells. Overall, AZD2014 showed significant antitumour effects. Thereby, the current study highlights a reliable theoretical basis for the clinical application of AZD2014 in both Doc-sensitive and Doc-resistant CRPCs.
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Benzamidas/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Alvo Mecanístico do Complexo 1 de Rapamicina/antagonistas & inibidores , Alvo Mecanístico do Complexo 2 de Rapamicina/antagonistas & inibidores , Morfolinas/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirimidinas/farmacologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células , Docetaxel/farmacologia , Relação Dose-Resposta a Droga , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos , Imunofenotipagem , Masculino , Neoplasias de Próstata Resistentes à Castração , Transdução de Sinais/efeitos dos fármacosRESUMO
BACKGROUND: Heterogeneous nuclear ribonucleoprotein K (HnRNPK) is a nucleic acid-binding protein that regulates diverse biological events. Pathologically, HnRNPK proteins are frequently overexpressed and clinically correlated with poor prognosis in various types of human cancers and are therefore pursued as attractive therapeutic targets for select patients. However, both the transcriptional regulation and degradation of HnRNPK in prostate cancer remain poorly understood. METHODS: qRT-PCR was used to detect the expression of HnRNPK mRNA and miRNA; Immunoblots and immunohistochemical assays were used to determine the levels of HnRNPK and other proteins. Flow cytometry was used to investigate cell cycle stage. MTS and clonogenic assays were used to investigate cell proliferation. Immunoprecipitation was used to analyse the interaction between SPOP and HnRNPK. A prostate carcinoma xenograft mouse model was used to detect the in vivo effects of HnRNPK and miRNA. RESULTS: In the present study, we noted that HnRNPK emerged as an important player in the carcinogenesis process of prostate cancer. miR-206 and miR-613 suppressed HnRNPK expression by targeting its 3'-UTR in PrCa cell lines in which HnRNPK is overexpressed. To explore the potential biological function, proliferation and colony formation of PrCa cells in vitro and tumor growth in vivo were also dramatically suppressed upon reintroduction of miR-206/miR-613. We have further provided evidence that Cullin 3 SPOP is a novel upstream E3 ubiquitin ligase complex that governs HnRNPK protein stability and oncogenic functions by promoting the degradation of HnRNPK in polyubiquitination-dependent proteolysis in the prostate cancer setting. Moreover, prostate cancer-associated SPOP mutants fail to interact with and promote the destruction of HnRNPK proteins. CONCLUSION: Our findings reveal new posttranscriptional and posttranslational modification mechanisms of HnRNPK regulation via miR-206/miR-613 and SPOP, respectively. More importantly, given the critical oncogenic role of HnRNPK and the high frequency of SPOP mutations in prostate cancer, our results provide a molecular rationale for the clinical investigation of novel strategies to combat prostate cancer based on SPOP genetic status.
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PURPOSE: To assess corneal densitometry in patients with Fabry disease (FD) and to compare corneal densitometry differences in FD patients to different corneal manifestations. METHODS: Ten participants (20 eyes) with FD and 10 age-matched healthy volunteers (20 eyes) were recruited. All participants were assessed by standardized ophthalmic examinations and the corneal densitometry analysis by Pentacam HR. Densitometry measurements were analyzed in standardized grayscale units. RESULTS: Seven patients developed conjunctival vessel tortuosity, cornea verticillata appeared in 6 patients, and two patients had Fabry cataract. Retinal vessel tortuosity occurred in 4 patients, and dilation of retinal vessels appeared in 3 patients, all symptoms occurred in both eyes. The first diagnosis of FD up to examination was 4.7 ± 3.23 years, and first ERT up to examination was 2.6 ± 2.27 years. The initial time to diagnosis was negatively related to the corneal densitometry value of the 0-2-mm (r = - 0.556, p = 0.011) and 2-6-mm (r = - 0.482, p = 0.032) zones in the posterior layer. FD group have significantly higher corneal densitometry in anterior 0-2-mm zone and 2-10-mm zone anterior and posterior layer than the control group (p ≤ 0.035, respectively). When divided into two groups by the existence of cornea verticillata, there was a statistically significant difference in the anterior layer, 6-10-mm zone (p = 0.031); in the central layer, 0-2 mm (p = 0.012), 2-6 mm (p = 0.001), 6-10 mm (p = 0.002), and total (p = 0.002); and in the posterior layer, 6-10 mm (p = 0.004) and total (p = 0.002). CONCLUSIONS: FD patients show higher corneal densitometry, and corneal densitometry may have potential for early diagnosis and reminding progress of FD.
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Doença de Fabry , Túnica Conjuntiva , Córnea , Densitometria , Diagnóstico Precoce , Doença de Fabry/diagnóstico , HumanosRESUMO
INTRODUCTION: Prostatic stromal tumor of uncertain malignant potential (STUMP) is a rare disease that may coexist with prostate stromal sarcoma (PSS). We aimed to analyze the histological and clinical features of STUMP. METHODS: Twenty-three patients diagnosed with STUMP from 2008 to 2019 were included. Clinicopathological and follow-up information was collected. In the subgroup analysis, we divided the patients into a pure STUMP group (N = 18) and a mixed STUMP (STUMP coexisting with PSS) group (N = 5). Student's t test was used to compare the 2 groups. RESULTS: Patients had a mean age of 55.5 ± 19.4 years and an average follow-up time of 42.3 months. The mean prostate volume was 109.2 ± 73.5 cm3, and the mean prostate-specific antigen was 8.03 ± 10.5 ng/mL. In the subgroup analysis, 16.7% (2/12) of pure STUMP patients had disease progression, while 100% (3/3) of mixed STUMP patients suffered from recurrence. Compared with the pure STUMP group, the mixed STUMP group was younger (37.2 vs. 60.6 years, p = 0.013) and had lower expression of estrogen receptor and progesterone receptor (p = 0.004 and p < 0.001, respectively). CONCLUSION: STUMP is a rare disease with a relatively good prognosis. However, there is still a possibility of disease progression or coexistence with stromal sarcoma. Timely diagnosis and regular monitoring may be helpful in improving treatment outcomes.
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Neoplasias da Próstata/patologia , Sarcoma/patologia , Adulto , Idoso , China , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Three-dimensional (3D) stereophotography area measurements are essential for describing morphology in the periocular region. However, its reliability has not yet been sufficiently validated. The objective of this study was to evaluate the reliability of 3D stereophotogrammetric area measurements in the periocular region. Forty healthy volunteers had five flat paper objects placed at each of the seven periocular positions including the endocanthion and the upper medial, upper middle, upper lateral, lower medial, lower middle, and the lower lateral eyelid. Two series of photographic images were captured twice by the same investigator. Each image of the first series was measured twice by the same rater, while images of both series were measured once by a second rater. Differences between these measurements were calculated, and the intrarater, interrater, and intramethod reliability was evaluated for intraclass correlation coefficients (ICCs), mean absolute differences (MADs), technical errors of measurements (TEMs), relative errors of measurements (REMs), and relative TEM (rTEM). Our results showed that 21.2% of all ICCs were considered as excellent, 45.5% were good, 27.3% were moderate, and 6.1% were poor. The interrater ICC for the endocanthion location was 0.4% on a low level. MAD values for all objects were less than 0.3 mm2, all TEM were less than 1 mm2, the REM and rTEM were less than 2% for all objects, showing high reliability. 3D stereophotogrammetry is a highly reliable system for periocular area measurements and may be used in the clinical routine for planning oculoplastic surgeries and for evaluating changes in periocular morphology.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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Face , Fotogrametria , Pálpebras , Humanos , Fotografação , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Assessment of MCT laxity is critical to the surgery options. Our study aimed to analyze the reliability of measuring medial canthal tendon (MCT) laxity by using a novel standardized three-dimensional lateral distraction test (3D-LDT). METHODS: Forty-eight Caucasian volunteers (25 males and 23 females, 96 eyes) between 22 and 84 years of age (55.6 ± 18.6 years old) were included in our study. From a neutral position, the lower eyelid was gently pulled laterally along a horizontal line to define the most distracted position of the lower punctum. Both in the neutral and distracted position, standardized 3D images were acquired for each subject by two observers, and each image were measured twice by two raters. Four landmarks and six corresponding linear measurements were evaluated for intra-rater, inter-rater, and inter-method reliability. RESULTS: Intra-rater, inter-rater and inter-method reliability analyses of 3D-LDT revealed an intraclass correlation of more than 95%, a mean absolute difference of less than 1 mm, and a technical error of measurement of less than 1 mm. Measurements of relative error (2.59-12.04%) and relative technical error (1.83-16.05%) for the inter-landmarks distance from pupil center to the lower punctum were higher than those from limbus nasal center to the lower punctum (6.13-30.39 and 4.34-26.85%, respectively). CONCLUSIONS: This study provided high reliability of the three-dimensional lateral distraction test (3D-LDT) for assessing medial canthal tendon (MCT) laxity, which were never evaluated by digital imaging system. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Blefaroplastia , Pálpebras , Adulto , Idoso , Pálpebras/cirurgia , Feminino , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Reprodutibilidade dos Testes , Tendões/cirurgiaRESUMO
PURPOSE: To introduce and evaluate a minimally-invasive endoscopy-guided transcaruncular laser-assisted StopLoss Jones tube (SLJT) implantation technique for severe canalicular obstructions in primary surgeries. METHODS: We retrospectively identified 12 adult patients (12 eyes) with severe epiphora secondary to long-segment canalicular obstructions. All the 12 eyes underwent an endoscopy-guided transcaruncular SLJT implantation with an 810-nm diode laser's assistance as the primary surgical approach. Surgical and functional success rates, intraoperative and postoperative complications, as well as the need for secondary surgery, are evaluated. RESULTS: Primary surgical success was achieved in 11 of the 12 cases (92%); one patient (8%) required secondary surgery to replace an SLJT with a shorter one. Ultimately, all cases showed well-placed functioning tubes. Three of the 12 cases (25%) presented conjunctival scarring, conjunctival granulation tissue, with or without tube-associated irritation of the ocular surface. We observed no sink-in, extrusion, nor crack of the tube. Complete functional success was achieved in 83%, and moderate functional success in 17% of all patients. The functionally unsuccessful outcome was not present in this study. CONCLUSION: Endoscopy-guided transcaruncular diode laser-assisted SLJT implantation seems to be a promising minimally invasive approach for primary treatment of severe canalicular dacryostenosis. This novel technique shows high functional success rates. It seems to avoid the risk of tube malposition and extrusion, septal and turbinate injury, nasal adhesion, drainage failure, ethmoiditis, postoperative bleeding, and cutaneous scars.
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Dacriocistorinostomia , Obstrução dos Ductos Lacrimais , Adulto , Endoscopia , Humanos , Intubação , Obstrução dos Ductos Lacrimais/diagnóstico , Lasers Semicondutores/uso terapêutico , Estudos RetrospectivosRESUMO
BACKGROUND: ADAMTS5 has been reported to be involved in the progression of several human tumors. Nevertheless, the role of ADAMTS5 in gastric cancer (GC) remains poorly defined. METHODS: ADAMTS5 expression levels were analyzed by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) in GC cell lines and tissues, and the correlations between ADAMTS5 expression and clinicopathological features and survival were also examined. In vitro assays, including transwell assays, wound healing assays and cell adhesion assays, were employed to further explore the biological functions of ADAMTS5. A MAP kinase pathway microarray was used to identify the underlying mechanisms. The expression of ADAMTS5 and ETS1 and the microvessel density (MVD) were also analyzed using IHC to determine correlations with angiogenesis in GC. RESULTS: ADAMTS5 expression was downregulated in gastric cancer tissues. Low expression of ADAMTS5 was associated with gender, histological type, degree of differentiation, M stage, TNM stage and vascular invasion, and was also an independent indicator of a poor prognosis for patients with GC. ADAMTS5 overexpression markedly inhibited GC cell migration and invasion and enhanced cell adhesion to the extracellular matrix (ECM), whereas knockdown of ADAMTS5 exerted the opposite effects. Furthermore, the ADAMTS5 expression status was negatively correlated with ETS1 expression and MVD. CONCLUSION: ADAMTS5 is downregulated in GC and suppresses tumor metastasis and angiogenesis by inhibiting ETS1-mediated changes in MVD and potentially acts as a novel prognostic marker and a potential therapeutic target in human GC.
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Proteína ADAMTS5/biossíntese , Biomarcadores Tumorais/análise , Movimento Celular/fisiologia , Invasividade Neoplásica/patologia , Neovascularização Patológica/metabolismo , Neoplasias Gástricas/patologia , Adulto , Idoso , Progressão da Doença , Feminino , Genes Supressores de Tumor , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
PURPOSE: To establish the necessity of routine histopathologic examination of specimens from hemorrhoids and anal fistula that are diagnosed preoperatively. METHODS: We reviewed histopathologic reports from hemorrhoidectomy and anal fistula excision operations performed between 2007 and 2011 in the sixth affiliated hospital of Sun Yat-sen University and Guangdong Province Traditional Chinese Medical Hospital. We evaluated the incidence of unexpected pathologic malignancy and its impact on postoperative management. RESULTS: Among the 10532 patients recruited, 8308 had undergone hemorrhoidectomy and 2224 had undergone excision of an anal fistula. Unexpected pathologic malignancy was discovered in 17 specimens (0.16 %). Overall and subgroup analysis for risk factors of malignant detection revealed unexpected pathologic malignancy was more likely to be found in people over the age of 60 years (OR = 5.516, P = 0.002 overall and OR = 5.442, P = 0.007 for hemorrhoids). CONCLUSION: Routine histopathologic examination of specimens from patients undergoing hemorrhoid or anal fistula surgery is of value for identifying unexpected pathologic malignancy. An age older than 60 years may be a remarkable risk factor.
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Neoplasias do Ânus/diagnóstico , Neoplasias do Ânus/epidemiologia , Testes Diagnósticos de Rotina/estatística & dados numéricos , Hemorroidas/patologia , Fístula Retal/patologia , Neoplasias Retais/diagnóstico , Neoplasias Retais/epidemiologia , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Neoplasias do Ânus/patologia , Feminino , Seguimentos , Hemorroidas/cirurgia , Humanos , Incidência , Achados Incidentais , Masculino , Pessoa de Meia-Idade , Fístula Retal/cirurgia , Neoplasias Retais/patologia , Fatores de Risco , Fatores de TempoRESUMO
Benign prostatic hyperplasia (BPH) occurs when there is an imbalance between the proliferation and death of prostate cells, which is regulated tightly by estrogen signaling. However, the role of G protein-coupled estrogen receptor (GPER) in prostate cell survival remains ambiguous. In this study, we observed that prostates with epithelial hyperplasia showed increased yes-associated protein 1 (YAP) expression and decreased levels of estrogen and GPER. Blocking YAP through genetic or drug interventions led to reduced proliferation and increased apoptosis in the prostate epithelial cells. Interestingly, GPER agonists produced similar effects. GPER activation enhanced the phosphorylation and degradation of YAP, which was crucial for suppressing cell proliferation and survival. The Gαs/cAMP/PKA/LATS pathway, downstream of GPER, transmitted signals that facilitated YAP inhibition. This study investigated the interaction between GPER and YAP in the prostate epithelial cells and its contribution to BPH development. It lays the groundwork for future research on developing BPH treatments.
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Corneal wound healing in diabetic patients is usually delayed and accompanied by excessive inflammation. However, the underlying cellular and molecular mechanisms remain poorly understood. Here, we found that somatostatin (SST), an immunosuppressive peptide produced by corneal nerve fibers, was significantly reduced in streptozotocin-induced diabetic mice. In addition, we discovered that topical administration of exogenous SST significantly improved re-epithelialization and nerve regeneration following diabetic corneal epithelial abrasion. Further analysis showed that topical SST significantly reduced the expression of injury inflammation-related genes, inhibited neutrophil infiltration, and shifted macrophage polarization from pro-inflammatory M1 to anti-inflammatory M2 in diabetic corneas' healing. Moreover, the application of L-817,818, an agonist of the SST receptor type 5 subtype, significantly reduced the inflammatory response following epithelial injury and markedly improved the process of re-epithelialization and nerve regeneration in mice. Taken together, these data suggest that activation of the SST-SST receptor type 5 pathway significantly ameliorates diabetes-induced abnormalities in corneal wound repair in mice. Targeting this pathway may provide a novel strategy to restore impaired corneal wound closure and nerve regeneration in diabetic patients.
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Córnea , Lesões da Córnea , Diabetes Mellitus Experimental , Receptores de Somatostatina , Transdução de Sinais , Somatostatina , Cicatrização , Animais , Camundongos , Somatostatina/metabolismo , Córnea/patologia , Córnea/metabolismo , Lesões da Córnea/metabolismo , Receptores de Somatostatina/metabolismo , Masculino , Modelos Animais de Doenças , Humanos , Macrófagos/metabolismo , Macrófagos/imunologia , Camundongos Endogâmicos C57BL , Regeneração NervosaRESUMO
Prostate cancer (PCa) poses a serious burden to men. Interferon-ß (IFN-ß) is implicated in cancer cell growth. This study hence explored the regulation of IFN-ß-modified human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) in PCa cells. In vitro-cultured hUCMSCs were transfected with pcDNA3.1-IFN-ß plasmid or IFN-ß siRNA. hUCMSC-Exos were extracted by ultracentrifugation and identified. PCa cells (PC3 and LNCap) were treated with Exos. Cellular internalization of Exos by cells was detected by uptake assay. Cell proliferation, cycle, and apoptosis were evaluated by CCK-8, EdU staining, and flow cytometry. Levels of cell cycle-related proteins (cyclin D/cyclin E) were determined by Western blot. The effect of IFN-ß-modified hUCMSC-Exos in vivo was analyzed. IFN-ß-modified hUCMSC-Exos (Exooe-IFN-ß or Exosi-IFN-ß) were successfully isolated. IFN-ß was encapsulated in Exos, and PCa cells could uptake Exos. After treating with Exooe-IFN-ß, PCa cell proliferation was impeded, the percentage of cells in the G0/G1 phase, cyclin D/cyclin E levels, and cell apoptotic rate were elevated, while cells treated with Exooe-IFN-ß exhibited contrary trends. IFN-ß-modified hUCMSC-Exos reduced PCa tumor size and weight in vivo. Conjointly, IFN-ß-modified hUCMSC-Exos suppress PCa cell proliferation and facilitate apoptosis.
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Exossomos , Células-Tronco Mesenquimais , Neoplasias da Próstata , Masculino , Humanos , Ciclina E/metabolismo , Interferon beta/metabolismo , Exossomos/genética , Exossomos/metabolismo , Apoptose/genética , Fatores Imunológicos/metabolismo , Neoplasias da Próstata/metabolismo , Proliferação de Células , Cordão Umbilical/metabolismo , Ciclina D/metabolismoRESUMO
Fecal immunochemical test (FIT) is often used for preselection for colonoscopy, but FIT has nonoptimal sensitivity. Selection of study participant for colonoscopy based on the result of combining FIT with risk factors could improve the sensitivity of a screening program. We aimed to develop a risk prediction system of colorectal neoplasia among asymptomatic Chinese subjects. A total of 6265 asymptomatic participants with age between 50 and 70 years were invited to undergo colonoscopy screening. They were also asked to take FIT and complete a questionnaire for collecting information on risk factors. Independent risk factors were identified by binary logistic regression for colorectal neoplasia. A risk score model was developed by using the odds ratios of significant risk factors. The scoring system was divided into two groups of risk: negative risk and positive risk. The performance of the risk score model in terms of predicting colorectal neoplasia was evaluated. Of the 1786 colonoscopy screening participants, 1546 completed FIT and questionnaires. A total of 462 cases of neoplasia were detected. Based on the scoring stratification, 966 (62.5%) participants were in negative risk tier and 580 (37.5%) were in positive risk tier. The incidence of colorectal neoplasia in negative risk and positive risk groups was 18.4 and 49.0%, respectively. Risk stratification model has better ability to discriminate those with or without colorectal neoplasia than FIT-only model. Classification improved significantly with risk stratification-based screening (net reclassification improvement = 0.064, P = 0.032). Risk stratification system increases the predictive value of FIT-based screening and is useful for preselection for colonoscopy in colorectal cancer screening program.
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Neoplasias Colorretais , População do Leste Asiático , Humanos , Pessoa de Meia-Idade , Idoso , Medição de Risco , Fatores de Risco , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/etiologia , Colonoscopia , Sangue Oculto , Detecção Precoce de Câncer/efeitos adversos , Fezes , Programas de Rastreamento/efeitos adversosRESUMO
Blood glucose has been demonstrated to serve as prognostic indicators in various malignancies. This study aimed to explore the relationship between fasting blood glucose (FBG) levels and the prognosis in patients with gastrointestinal stromal tumor (GIST) undergoing complete resection. Data were retrospectively collected from 256 patients with primary GIST underwent complete surgical resection or endoscopic excision. Patients were stratified into euglycemic group and hyperglycemic group. Patients' characteristics between groups were compared. Cox regression model was conducted to identify independent prognostic factors of disease-free survival (DFS). Both univariate analysis and multivariate analyses revealed that FBG ≥ 100 mg/dl was associated with poor outcomes. Patients with FBG ≥ 100 mg/dl tended to have more adverse features, more likely to suffer recurrence and a worse 5-year DFS than patients with FBG < 100 mg/dl. Moreover, FBG levels helped distinguishing between patients with different survival outcomes in different risk categories defined by modified NIH systems. Our data provided the evidence that FBG is a useful prediction marker prognosis in patients with GIST undergoing curative surgery.
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Tumores do Estroma Gastrointestinal , Humanos , Tumores do Estroma Gastrointestinal/patologia , Glicemia , Estudos Retrospectivos , Prognóstico , Jejum , Recidiva Local de NeoplasiaRESUMO
Glioblastoma downregulated RNA (GLIDR) is a newly discovered long non-coding RNA (lncRNA) that its increased expression indicates a poor prognosis of prostate cancer (PCa). However, the effect of GLIDR on PCa cells is not clear. Our study investigated the role and molecular mechanism of GLIDR in PCa cells. The results showed that GLIDR expression levels were higher in PCa samples and cells than in control. GLIDR could regulate the invasive potential, epithelial-to-mesenchymal transition (EMT) and proliferation in PC-3 and LnCaP cells. Besides, GLIDR could weaken the inhibitory effects of miR-128-3p on invasion, EMT and proliferation in PCa cells. Western blotting proved that miR-128-3p affected the expression of EMT markers, such as E-cadherin, Snail and N-cadherin, and GLIDR could reversed the effects of miR-128-3p on the expression levels of EMT markers in PCa cells. In addition, knockdown of miR-128-3p stimulated the invasion, EMT, and proliferation in PCa cells, whereas these effects were reversed when GLIDR expression was knocked down. GLIDR knockdown inhibited the invasion, EMT, and proliferation in PCa cells, and GLIDR was shown to sponge miR-128-3p. Together, these results highlight GLIDR as a potential therapeutic target for the PCa treatment.