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Ovarian cancer (OC) is among the most common and deadly solid malignancies in women. Despite many advances in OC research, the incidence of OC continues to rise, and its pathogenesis remains largely unknown. Herein, we elucidated the function of hsa_circ_0061179 in OC. The levels of hsa_circ_0061179, miR-143-3p, TIMELESS, and DNA damage repair-related proteins in OC or normal ovarian tissues and cells were measured using real-time quantitative polymerase chain reaction and immunoblotting. The biological effects of hsa_circ_0061179 and miR-143-3p on proliferation, clone formation, DNA damage, and apoptosis of OC cells were detected by the cell counting kit-8 assay, 5-methylethyl-2'-deoxyuridine, flow cytometry, the comet assay, and immunofluorescence staining combined with the confocal microscopy. The interaction among hsa_circ_0061179, miR-143-3p, and TIMELESS was validated by the luciferase reporter assay. Mice tumor xenograft models were used to evaluate the influence of hsa_circ_0061179 on OC growth in vivo. We found that human OC biospecimens expressed higher levels of hsa_circ_0061179 and lower levels of miR-143-3p. Hsa_circ_0061179 was found to bind with miR-143-3p, which directly targets TIMELESS. Hsa_circ_0061179 knockdown or miR-143-3p overexpression suppressed the proliferation and clone formation of OC cells and increased DNA damage and apoptosis of OC cells via the miR-143-3p/TIMELESS axis. Furthermore, we demonstrated that METTL3 could direct the formation of has_circ_0061179 through a specific m6A modification site. YTHDC1 facilitated the cytoplasmic transfer of has_circ_0061179 by directly binding to the modified m6A site. Our findings suggest that hsa_circ_0061179 acts as the sponge of miR-143-3p to activate TIMELESS signaling and inhibits DNA damage and apoptosis in OC cells.
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Apoptosis , Proliferación Celular , Daño del ADN , Regulación Neoplásica de la Expresión Génica , MicroARNs , Neoplasias Ováricas , ARN Circular , Animales , Femenino , Humanos , Ratones , Adenosina/análogos & derivados , Línea Celular Tumoral , Metiltransferasas , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , ARN Circular/genética , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
OBJECTIVE: Ferroptosis is a reactive oxygen species (ROS)- and iron-dependent form of non-apoptotic cell death process. Previous studies have demonstrated that ferroptosis participates in the development of inflammatory arthritis. However, the role of ferroptosis in rheumatoid arthritis (RA) inflammatory hypoxic joints remains unclear. This study sought to explore the underlying mechanism of ferroptosis on lipopolysaccharide (LPS)-induced RA fibroblast-like synoviocytes (FLSs). METHODS: FLSs, isolated from patients with RA, were treated with LPS and ferroptosis inducer (erastin and RSL-3), and ferroptosis inhibitor (Fer-1 and DFO), respectively. The cell viability was measured by CCK-8. The cell death was detected by flow cytometer. The proteins level were tested by Western blot. The cytosolic ROS and lipid peroxidation were determined using DCFH-DA and C11-BODIPY581/591 fluorescence probes, respectively. The small interfering RNA (siRNA) was used to knock down related proteins. The levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), iron, inflammatory cytokines (IL6 and IL8), and LDH were analyzed by commercial kits. RESULTS: Ferroptosis was activated by LPS in RA FLS with increased cellular damage, ROS and lipid peroxidation, intracellular Fe and IL8, which can be further amplified by ferroptosis inducer (erastin and RSL-3) and inhibited by ferroptosis inhibitor (Fer-1 and DFO). Mechanistically, LPS triggered ferroptosis via NCOA4-mediated ferritinophagy in RA FLSs, and knockdown of NCOA4 strikingly prevent the process of ferroptosis. Intriguingly, LPS-induced RA FLSs became insensitive to ferroptosis and NCOA4-mediated ferritinophagy under hypoxia compared with normoxia. Knockdown of HIF-1α reverted ferroptosis and ferritinophagy evoking by LPS-induced RA FLSs inflammation under hypoxia. In addition, low dose of auranofin (AUR) induced re-sensitization of ferroptosis and ferritinophagy through inhibiting the expression of HIF-1α under hypoxia. CONCLUSIONS: NCOA4-mediated ferritinophagy was a key driver of ferroptosis in inflammatory RA FLSs. The suppression of NCOA4-mediated ferritinophagy protected RA FLSs from ferroptosis in LPS-induced inflammation under hypoxia. Targeting HIF-1α/NCOA4 and ferroptosis could be an effective and valuable therapeutic strategy for synovium hyperplasia in the patients with RA.
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Artritis Reumatoide , Ferroptosis , Sinoviocitos , Humanos , Lipopolisacáridos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Interleucina-8/metabolismo , Artritis Reumatoide/metabolismo , Inflamación/inducido químicamente , Inflamación/metabolismo , Hipoxia/metabolismo , Factores de Transcripción/metabolismo , ARN Interferente Pequeño/genética , Fibroblastos/metabolismo , Hierro/metabolismo , Coactivadores de Receptor Nuclear/genética , Coactivadores de Receptor Nuclear/metabolismoRESUMEN
OBJECTIVE: We aimed to compare the 5-year oncological outcomes of laparoscopic/abdominal radical hysterectomy (LRH/ARH) in patients with cervical adenosquamous carcinoma at stage IA2 to IIA2 based on the 2009 or 2018 International Federation of Gynecology and Obstetrics (FIGO) staging criteria. METHODS: Based on the clinical diagnosis and treatment of cervical cancer in China (Four C) database, Cox risk regression models were applied to analyze tumor prognosis treated with ARH/LRH in FIGO 2009 and 2018 IA2-IIA2 patients and stratified findings according to tumor diameter (≤4 and >4 cm subgroups). And to avoid bias, propensity score matching (PSM) was also used for the cohort study. RESULTS: Based on FIGO 2009 staging criteria (n = 474), there was no significant difference between the ARH and LRH groups in 5-year disease-free survival (DFS) or overall survival (OS). Lymph node metastasis was a risk factor for 5-year DFS in this stage. After PSM, lymphovascular space invasion (LVSI) was an independent risk factor for 5-year OS in the tumors ≤4 cm subgroup. Based on FIGO2018 staging criteria (n = 322), cervical interstitial infiltration depth was an independent risk factor for 5-year OS in the total population and the tumor diameter ≤4 cm subgroup. CONCLUSIONS: Laparoscopic surgery was not a risk factor affecting the oncologic prognosis of adenosquamous carcinoma of the cervix based on either FIGO 2009 or 2018 staging of stage IA2-IIA2. In addition, LRH may be considered for patients with early-stage cervical adenosquamous carcinoma.
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Carcinoma Adenoescamoso , Laparoscopía , Neoplasias del Cuello Uterino , Femenino , Humanos , Estudios Retrospectivos , Neoplasias del Cuello Uterino/patología , Estudios de Cohortes , Carcinoma Adenoescamoso/cirugía , Carcinoma Adenoescamoso/patología , Estadificación de Neoplasias , Supervivencia sin Enfermedad , HisterectomíaRESUMEN
PURPOSE: The COVID-19 pandemic imposed unexpected disruptions to anatomical educational practice, the teaching of regional anatomy for international students which has changed to an online format and faces various challenges. The challenges include creating online education homogeneous/equivalent to offline education, introducing local culture to international students, and educating students in medical humanities and ethics. METHODS: To address these problems, the teaching staff integrated medical humanities and local culture into nonsynchronous online teaching of regional anatomy. RESULTS: The nonsynchronous online teaching with interpreted videos of dissections does not significantly affect the experimental and total scores of regional anatomy courses for international students. Integrating medical humanities and local culture into this teaching model is appreciated by them and also has a good teaching effect. CONCLUSION: Students not only gained professional knowledge but also obtained enhanced exposure to local culture and professional spirit from this regional anatomy education.
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Anatomía , COVID-19 , Educación de Pregrado en Medicina , Estudiantes de Medicina , Humanos , Anatomía Regional , COVID-19/epidemiología , COVID-19/prevención & control , Pandemias/prevención & control , Curriculum , Humanidades/educación , Anatomía/educación , EnseñanzaRESUMEN
Stroke is the most common, deadly, and complicating neurological disease. Many studies have shown that the levels of some acute inflammatory reactants in people with ischemic stroke are higher than average. Therefore, in this study, three acute inflammatory reactants, i.e., C-reactive protein, Serum cystatin C, and carbohydrate antigen 125, were evaluated in patients with acute ischemic stroke to consider the association between these serums with intra and extra-cerebral vessels stenosis. In this cross-sectional study, 90 patients with non-embolic ischemic stroke were evaluated. The diagnosis was by physical examination, rejection of emboli, and brain imaging. Blood samples were taken in the first 24 hours of a stroke. ELISA test was used to measure CRP, Serum cystatin C, and CA125. Doppler ultrasound of cerebral arteries was also performed in the first five days. Independent chi-square and t-tests were used to analyze the data. The result of CRP level in patients with stenosis was 7.58±1.33µg/ml and in patients without stenosis was 4.10±1.75µg/ml (p = 0.004). Also, there was a significant relationship between serum CRP level and stenosis (p = 0.003). In patients with abnormal CRP, the internal carotid artery, middle cerebral artery, and anterior cerebral artery were the most involved. In patients with normal CRP, the most involved arteries were the anterior cerebral artery, internal carotid artery, and middle cerebral artery, respectively. There was a significant relationship between serum CRP level and the location of internal carotid artery stenosis (p = 0.015) and middle cerebral artery (p = 0.006). The amount of cystatin C between the normal CRP and abnormal CRP groups was statistically significant so that its concentration in the normal group was less than in the abnormal group (p = 0.04). The results of measuring the serum concentration of carbohydrate antigen 125 showed that the serum level in the normal group was statistically lower than in the abnormal group (P = 0.02). The results showed that stenosis of the internal carotid artery and middle cerebral artery is more common in patients with ischemic stroke with high serum CRP levels. This finding suggests that abnormal CRP may be more associated with narrowing some cerebral arteries.
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Proteína C-Reactiva , Antígeno Ca-125 , Cistatina C , Accidente Cerebrovascular Isquémico , Proteínas de la Membrana , Proteína C-Reactiva/análisis , Antígeno Ca-125/sangre , Constricción Patológica , Estudios Transversales , Cistatina C/sangre , Humanos , Accidente Cerebrovascular Isquémico/sangre , Proteínas de la Membrana/sangre , Factores de RiesgoRESUMEN
Hemoglobinopathies are the most common monogenic disorders worldwide. Substantial effort has been made to establish databases to record complete mutation spectra causing or modifying this group of diseases. We present a variant database which couples an online auxiliary diagnosis and at-risk assessment system for hemoglobinopathies (DASH). The database was integrated into the Leiden Open Variation Database (LOVD), in which we included all reported variants focusing on a Chinese population by literature peer review-curation and existing databases, such as HbVar and IthaGenes. In addition, comprehensive mutation data generated by high-throughput sequencing of 2,087 hemoglobinopathy patients and 20,222 general individuals from southern China were also incorporated into the database. These sequencing data enabled us to observe disease-causing and modifier variants responsible for hemoglobinopathies in bulk. Currently, 371 unique variants have been recorded; 265 of 371 were described as disease-causing variants, whereas 106 were defined as modifier variants, including 34 functional variants identified by a quantitative trait association study of this high-throughput sequencing data. Due to the availability of a comprehensive phenotype-genotype data set, DASH has been established to automatically provide accurate suggestions on diagnosis and genetic counseling of hemoglobinopathies. LOVD-DASH will inspire us to deal with clinical genotyping and molecular screening for other Mendelian disorders.
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Bases de Datos Genéticas , Hemoglobinopatías/genética , Mutación , China , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Medición de Riesgo , Análisis de Secuencia de ADNRESUMEN
Pre-eclampsia is associated with inadequate placental blood flow and placental ischaemia. Placental vascular tone is essential for maintaining adequate placental blood flow. Oxytocin is increased in placental system at late pregnancy and onset of labour, and presented strongly concentration-dependent contractions in placental vascular, suggesting that oxytocin could be involved in regulating placental vascular tone and circulation. However, information about the reactivity of oxytocin in pre-eclamptic placental vasculature is limited. This study used a large number of human placentas to reveal the pathophysiological changes and its underlying mechanisms of oxytocin-induced vasoconstrictions in placental vessels under pre-eclamptic condition. Present study found that oxytocin-induced contractions were significantly decreased in human pre-eclamptic placental vasculature, associated with a deactivated transcription of oxytocin receptor gene. The deactivated oxytocin receptor gene transcription was ascribed to a relatively higher DNA methylation status of CpG islands in oxytocin receptor gene promoter. This study was first to reveal that a hyper-methylation of CpG islands in oxytocin receptor gene promoter, leading to a relatively low pattern of oxytocin receptor expression, was responsible for the decreased sensitivity of oxytocin in pre-eclamptic placental vessels.
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Metilación de ADN/genética , Oxitocina/genética , Placenta/fisiología , Preeclampsia/genética , Receptores de Oxitocina/genética , Adulto , Islas de CpG/genética , Femenino , Humanos , Embarazo , Regiones Promotoras Genéticas/genética , Adulto JovenRESUMEN
OBJECTIVES: Fibroblast-like synoviocytes (FLS) play key roles in synovium hyperplasia and pannus formation in rheumatoid arthritis (RA). The present study was undertaken to explore the mechanisms that calreticulin (CRT) promoted anti-apoptosis of RA FLS. METHODS: The expression of CRT and anti-apoptotic proteins Bcl-XL and Mcl-1 in RA synovium were detected by immunohistochemistry. The expression of Bcl-XL and Mcl-1 in RA FLS by CRT were determined. The phosphorylation of Akt and STAT3 was detected by western blot. The effect of CRT on proliferation of RA FLS was examined by MTT assay. The ability of CRT to inhibit RA FLS apoptosis was assessed by flow cytometry. RESULTS: Increased expressions of CRT, Bcl-XL and Mcl-1 were detected in RA synovium compared with osteoarthritis (OA). Moreover, CRT expression correlated positively with Bcl-XL and Mcl-1 in RA, respectively. In vitro, CRT induced upregulation of Bcl-XL and Mcl-1 protein levels in RA FLS, in dose/time dependent manners. Upregulated expression of Bcl-XL and Mcl-1 induced by CRT were inhibited by PI3K/Akt or STAT3 pathways inhibitors in RA FLS, respectively. The increased phosphorylation levels of Akt and STAT3 were also detected with CRT incubation, in dose/time dependent manners. Additionally, CRT rescued apoptosis of RA FLS mediated by FasL. CONCLUSIONS: This study showed that upregulation of Bcl-XL and Mcl-1 expression in RA FLS by CRT were PI3K/Akt and STAT3 signal pathways dependent, and promoted the anti-apoptosis of RA FLS. Therefore, this may represent a therapeutic target for the treatment of RA.
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Apoptosis/efectos de los fármacos , Artritis Reumatoide/tratamiento farmacológico , Calreticulina/farmacología , Fibroblastos/efectos de los fármacos , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , Fosfatidilinositol 3-Quinasa/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Membrana Sinovial/efectos de los fármacos , Sinoviocitos/efectos de los fármacos , Proteína bcl-X/metabolismo , Artritis Reumatoide/enzimología , Artritis Reumatoide/patología , Calreticulina/metabolismo , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Fibroblastos/enzimología , Fibroblastos/patología , Humanos , Fosforilación , Membrana Sinovial/enzimología , Membrana Sinovial/patología , Sinoviocitos/enzimología , Sinoviocitos/patología , Regulación hacia ArribaRESUMEN
The heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1) was reported to participate in the development of a variety of tumors. BC15 is a DNA aptamer targeting hnRNP A1. Firstly, through sequence truncation, we identified 31-mer sequence BC15-31 as the core sequence of BC15 with a strong binding affinity and high selectivity to the hnRNP A1 protein. Isothymidine (isoT) modification was then applied for the structural optimization of BC15-31, systematic modification and biological evaluation were carried out. Incorporation of isoT in the 1,3 sites at the 5'-end of BC15-31 can significantly enhance the protein affinity. Chemical modifications close to the 3'-end can greatly improve the stability of the aptamer. Furthermore, BC15-31 modified with isoT at both the 5'-end and 3'-end displayed an additive effect with enhanced bioactivity and stability at the same time. Our study strategy on BC15 provides a useful guideline for chemical modification and optimization of the aptamer for further clinical application.
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Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/metabolismo , Ribonucleoproteína Nuclear Heterogénea A1/metabolismo , Timidina/química , Células A549 , Aptámeros de Nucleótidos/genética , Aptámeros de Nucleótidos/farmacología , Secuencia de Bases , Proliferación Celular/efectos de los fármacos , Células Hep G2 , Humanos , Unión Proteica , Relación Estructura-Actividad , Especificidad por SustratoRESUMEN
Recently, necroptosis, a form of programmed necrosis, has been widely studied. It has previously been shown that knockout of lysine 63 deubiquitinase CYLD significantly inhibits necroptosis in other cell lines, and serum response factor (SRF) could regulate CYLD gene expression through p38 mitogen-activated protein kinase (p38 MAPK). In the following study, we show oxygen-glucose deprivation (OGD) combined with a caspase inhibitor, ZVAD (OGD/ZVAD), induced CYLD protein expression in a time-dependent manner. Immunofluorescence studies showed that CYLD was localized strongly to the nucleus and weakly to the cytoplasm of neurons. The expression of CYLD in the cytoplasm, but not in the nucleus, was increased significantly upon OGD treatment. SB203580 (a p38 MAPK inhibitor) protected against neuronal injury induced by OGD/ZVAD treatment. More importantly, SB203580 decreased CYLD protein levels by inhibiting SRF phosphorylation and indirectly prevented SRF from binding to a CYLD promoter. We also found that cells with knockdown of SRF by short interfering RNA in a lentivirus vector tolerated OGD/ZVAD-induced necroptosis, when the expression of CYLD protein decreased. The results show that SB203580 prevented necroptosis induced by OGD/ZVAD injury by blocking a p38/CYLD dependent pathway.
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Apoptosis/fisiología , Cisteína Endopeptidasas/metabolismo , Glucosa/deficiencia , Sistema de Señalización de MAP Quinasas/fisiología , Neuronas/metabolismo , Oligopéptidos/toxicidad , Animales , Apoptosis/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Muerte Celular/fisiología , Hipoxia de la Célula/efectos de los fármacos , Hipoxia de la Célula/fisiología , Células Cultivadas , Corteza Cerebral/efectos de los fármacos , Corteza Cerebral/metabolismo , Corteza Cerebral/patología , Enzima Desubiquitinante CYLD , Femenino , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones , Necrosis/inducido químicamente , Necrosis/metabolismo , Necrosis/patología , Neuronas/efectos de los fármacos , Neuronas/patología , EmbarazoRESUMEN
MicroRNAs (miRNAs) are a class of non-coding small RNAs that consist of ≈ 22 nt and are involved in several biological processes by regulating target gene expression. MiR-138 has many biological functions and is often downregulated in cancers. Our results showed that overexpression of miR-138 downregulated target RMND5A (required for meiotic nuclear division 5 homolog A) and reduced Exportin-5 stability, which results in decreased levels of pre-miRNA nuclear export in HeLa cells. We also found that miR-138 could significantly inhibit HeLa cell migration by targeting RMND5A. Our study therefore identifies miR-138-RMND5A-Exportin-5 as a previously unknown miRNA processing regulatory pathway in HeLa cells.
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Proteínas Portadoras/genética , Regulación hacia Abajo , Carioferinas/metabolismo , MicroARNs/metabolismo , Procesamiento Postranscripcional del ARN , Transporte Activo de Núcleo Celular , Proteínas Portadoras/metabolismo , Movimiento Celular , Núcleo Celular/metabolismo , Células HeLa , Humanos , Estabilidad Proteica , Precursores del ARN/metabolismoRESUMEN
Clathrin has previously been implicated in Drosophila male fertility and spermatid individualization. To understand further the role of membrane transport in this process, we analyzed the phenotypes of mutations in Drosophila auxilin (aux), a regulator of clathrin function, in spermatogenesis. Like partial loss-of-function Clathrin heavy chain (Chc) mutants, aux mutant males are sterile and produce no mature sperm. The reproductive defects of aux males were rescued by male germ cell-specific expression of aux, indicating that auxilin function is required autonomously in the germ cells. Furthermore, this rescue depends on both the clathrin-binding and J domains, suggesting that the ability of Aux to bind clathrin and the Hsc70 ATPase is essential for sperm formation. aux mutant spermatids show a deficit in formation of the plasma membrane during elongation, which probably disrupts the subsequent coordinated migration of investment cones during individualization. In wild-type germ cells, GFP-tagged clathrin localized to clusters of vesicular structures near the Golgi. These structures also contained the Golgi-associated clathrin adaptor AP-1, suggesting that they were Golgi-derived. By contrast, in aux mutant cells, clathrin localized to abnormal patches surrounding the Golgi and its colocalization with AP-1 was disrupted. Based on these results, we propose that Golgi-derived clathrin-positive vesicles are normally required for sustaining the plasma membrane increase necessary for spermatid differentiation. Our data suggest that Aux participates in forming these Golgi-derived clathrin-positive vesicles and that Aux, therefore, has a role in the secretory pathway.
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Auxilinas/fisiología , Vesículas Cubiertas por Clatrina/fisiología , Drosophila/fisiología , Aparato de Golgi/fisiología , Espermatogénesis/fisiología , Animales , Animales Modificados Genéticamente , Auxilinas/genética , Auxilinas/metabolismo , Células Cultivadas , Vesículas Cubiertas por Clatrina/metabolismo , Citocinesis/genética , Citocinesis/fisiología , Drosophila/embriología , Drosophila/genética , Drosophila/metabolismo , Embrión no Mamífero , Femenino , Fertilidad/genética , Fertilidad/fisiología , Aparato de Golgi/genética , Aparato de Golgi/metabolismo , Masculino , Modelos Biológicos , Vías Secretoras/genética , Vías Secretoras/fisiología , Transducción de Señal/genética , Transducción de Señal/fisiología , Espermatogénesis/genéticaRESUMEN
Several studies have indicated that 1α,25-hydroxyvitamin D [1α,25(OH)2D3] inhibits the proliferation and metastasis of cancer cells through suppressing epithelial-mesenchymal transition. However, its influence on the translocation of ß-catenin remains unclear. In the present study, ovarian cancer stem-like cells (CSCs), including side population (SP) and CD44+/CD117+, were isolated from mouse ovarian surface epithelial (MOSE) cells with malignant transformation. The findings revealed that 1α,25(OH)2D3 obviously reduced the sphere-forming ability, as well as Notch1 and Klf levels. Moreover, the limiting dilution assay demonstrated that 1α,25(OH)2D3 effectively hindered the tumorigenesis of ovarian CSCs in vitro. Notably, treatment with 1α,25(OH)2D3 led to a substantial increase in the cell population of CD44+/CD117+ forming one tumor from ≤ 100 to 445 in orthotopic transplanted model, indicating a pronounced suppression of stemness of ovarian CSCs. Additionally, 1α,25(OH)2D3 robustly promoted the translocation of ß-catenin from the nuclear to the cytoplasm through directly binding to VDR, which resulted in decreased levels of c-Myc and CyclinD1 within late MOSE cells. Taken together, these results strongly supported the role of 1α,25(OH)2D3 in inhibiting stem-like properties in ovarian cancer cells by restraining nuclear translocation of ß-catenin, thereby offering a promising target for cancer therapeutics.
RESUMEN
Ovarian cancer (OC) represents the most prevalent malignancy of the female reproductive system. Its distinguishing features include a high aggressiveness, substantial morbidity and mortality, and a lack of apparent symptoms, which collectively pose significant challenges for early detection. Given that aberrant DNA methylation events leading to altered gene expression are characteristic of numerous tumor types, there has been extensive research into epigenetic mechanisms, particularly DNA methylation, in human cancers. In the context of OC, DNA methylation is often associated with the regulation of critical genes, such as BRCA1/2 and Rasassociation domain family 1A. Methylation modifications within the promoter regions of these genes not only contribute to the pathogenesis of OC, but also induce medication resistance and influence the prognosis of patients with OC. As such, a more indepth understanding of DNA methylation underpinning carcinogenesis could potentially facilitate the development of more effective therapeutic approaches for this intricate disease. The present review focuses on classical tumor suppressor genes, oncogenes, signaling pathways and associated microRNAs in an aim to elucidate the influence of DNA methylation on the development and progression of OC. The advantages and limitations of employing DNA methylation in the diagnosis, treatment and prevention of OC are also discussed. On the whole, the present literature review indicates that the DNA methylation of specific genes could potentially serve as a prognostic biomarker for OC and a therapeutic target for personalized treatment strategies. Further investigations in this field may yield more efficacious diagnostic and therapeutic alternatives for patients with OC.
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Metilación de ADN , Regulación Neoplásica de la Expresión Génica , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Epigénesis Genética , Pronóstico , MicroARNs/genética , Transducción de Señal/genética , Regiones Promotoras GenéticasRESUMEN
OBJECTIVE: The aim of our study was to investigate the contribution of serum calreticulin (CRT) in the assessment of disease activity in rheumatoid arthritis (RA). METHODS: Serum CRT levels were measured by ELISA in 70 patients with established RA, 30 systemic lupus erythematosus (SLE), 25 other autoimmune diseases, 20 osteoarthritis (OA), and 35 of healthy controls (HC). Correlations of CRT serum levels with disease activity [Disease Activity Score for 28 joints (DAS28)], erythrocyte sedimentation rate(ESR) and C-reactive protein (CRP) were assessed. Serum CRT levels were also detected in RA patients whose RF, anti-CCP and anti- MCV antibodies were positive and negative. RESULTS: Serum CRT levels in RA patients (4.817 ± 2.425 ng/ml) was significantly higher (P <0.05) compared with those in the serum of OA (3.574 ± 0.942 ng/ml), SLE (4.013 ± 1.536 ng/ml), other autoimmune diseases (3.882 ± 0.837 ng/ml) and HC (3.726 ± 0.627 ng/ml). Significant positive correlation of CRT with DAS28, ESR and CRP was found in RA patients. Furthermore, RA patients whose anti-CCP and anti-MCV antibodies were positive had higher levels of CRT (P < 0.01). CONCLUSION: Serum CRT levels were increased in patients with RA compared with those controls. Moreover, a significant correlation was observed between serum CRT levels and disease activity in RA. It might be used as a potential biomarker for clinical diagnosis and provide additional information regarding disease activity along with the traditional indices such as ESR and CRP.
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Artritis Reumatoide/sangre , Calreticulina/sangre , Anticuerpos/inmunología , Artritis Reumatoide/inmunología , Biomarcadores/sangre , Sedimentación Sanguínea , Proteína C-Reactiva/inmunología , Proteína C-Reactiva/metabolismo , Calreticulina/inmunología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The purpose of this study was to establish the three-dimensional (3D) architecture of the cutaneous angiosome for assessment and design of the perforator flaps. Two fresh cadavers were injected with carboxymethyl cellulose (CMC)/lead oxide and computed tomography (CT) scanned before and after the injection. The various parts of the cutaneous and subcutaneous tissue derived from one of the injected cadavers were also CT scanned. Three-dimensional reconstruction of the cutaneous angiosome and the two flap designs were performed using Materialise's Interactive Medical Image Control System (MIMICS). Both the reconstructed cutaneous angiosomes and the digital flaps can be displayed independently or in conjunction with bones, source arteries, and skin. The 3D architecture of the cutaneous angiosome ensures clear display of the spatial location, distribution range, and anastomoses relationship of the cutaneous perforators. In addition, the caliber, length, and position of a particular source artery are illustrated in the exact spatial location. As a result, the technique provides visualization of the general area and the expandable direction of a respective flap. This technique has the potential to play an important role in assessing perforator blood supply territory and in the design of new flaps.
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Angiografía/métodos , Vasos Sanguíneos/anatomía & histología , Procesamiento de Imagen Asistido por Computador/métodos , Piel/irrigación sanguínea , Tejido Subcutáneo/irrigación sanguínea , Cadáver , Humanos , Colgajos Quirúrgicos , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVE: The contribution of large vessel stenosis to the development of white matter hyperintensities (WMHs) has not been fully elucidated. This study aims to explore the correlation between ipsilateral white matter hyperintensities (WMHs) and the severity of large vessel stenosis in the anterior circulation and cerebral perfusion level, as well as analyze the factors influencing WMHs. METHODS: A cross-sectional study of 150 patients with unilateral anterior circulation large vessel stenosis of ≥50% was conducted. The severity of ipsilateral WMHs was assessed by Fazekas scale on T2-weighted image and/or fluid-attenuated inversion recovery MR imaging, vascular stenosis severity was evaluated on computed tomography angiography images, and the level of cerebral perfusion was rated according to a staging system for abnormal cerebral perfusion based on CTP results. The relationships between the stenosis severity, cerebral perfusion level and ipsilateral WMHs severity were analyzed. A multivariate logistic regression analysis was performed to determine the factors independently influencing WMHs. RESULTS: Among 150 patients (mean age, 63.12 ± 10.55 years), there was a statistically significant positive correlation between cerebral perfusion level and the severity of DWMHs and PWMHs (Gamma = 0.561, p < .001; Gamma = 0.600, p < .001), and a positive correlation between cerebral perfusion level and the severity of vascular stenosis (Gamma = 0.495, p < .001).While, there was no statistically significant correlation between the severity of vascular stenosis and the severity of DWMHs and PWMHs (Gamma = 0.188, p = .08; Gamma = 0.196, p = .06). The multivariate logistic regression analysis results demonstrated that age (OR = 1.047, 95% CI 1.003-1.093; p = .035), stroke/TIA history (OR = 2.880, 95% CI 1.154-7.190; p = .023) and stage II of cerebral perfusion (OR = 2.880, 95% CI 1.154-7.190; p = .023) were independent influencing factors on ipsilateral DWMHs. Age (OR = 1.051, 95% CI 1.009-1.094; p = .018), and stage II of cerebral perfusion (OR = 12.871, 95% CI 3.576-46.322; p < .001) were factors independently influencing ipsilateral PWMHs. CONCLUSION: White matter hyperintensities may be attributed to cerebral hypoperfusion secondary to vascular stenosis but not directly to the severity of stenosis in the large vessels of anterior circulation. Moreover, longitudinal studies with sequential imaging exams may further reveal the impact of cerebral perfusion secondary to vascular stenosis on the development and progression of WMHs.
Asunto(s)
Sustancia Blanca , Humanos , Persona de Mediana Edad , Anciano , Sustancia Blanca/diagnóstico por imagen , Constricción Patológica , Estudios Transversales , Imagen por Resonancia Magnética/métodos , Circulación CerebrovascularRESUMEN
Ovarian cancer (OC) is a deadly disease. The poor prognosis and high lethality of OC are attributed to its high degrees of aggressiveness, resistance to chemotherapy and recurrence rates. Calcium ion (Ca2+) signaling has received attention in recent years, as it appears to form an essential part of various aspects of cancer pathophysiology and is a potential therapeutic target for OC treatment. Disruption of normal Ca2+ signaling pathways can induce changes in cell cycle progression, apoptosis, proliferation and migration and invasion, leading to the development of the malignant phenotype of tumors. In the present review, the main roles of ion channel/receptor/pumptriggered Ca2+ signaling pathways located at the plasma membrane and organelle Ca2+ transport in OC are summarized. In addition, the potential of Ca2+ signaling as a novel target for the development of effective treatment strategies for OC was discussed. Furthering the understanding into the role of Ca2+ signaling in OC is expected to facilitated the identification of novel therapeutic targets and improved clinical outcomes for patients.
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Calcio , Neoplasias Ováricas , Humanos , Femenino , Neoplasias Ováricas/tratamiento farmacológico , Transducción de Señal , Agresión , ApoptosisRESUMEN
Although numerous epidemiological studies investigated the association between dietary fat intakes or serum lipid levels and ovarian cancer risk, a consistent and explicit conclusion for specific dietary fats or serum lipids that increase the risk of ovarian cancer is not available. In this study, a systematic review and meta-analysis were conducted to assess the key dietary fats and serum lipids that increased the risk of ovarian cancer. Databases such as PubMed, Web of Science, and EMBASE were searched for observational studies. A total of 41 studies met the inclusion criteria, including 18 cohort and 23 case-control studies (109,507 patients with ovarian cancer and 2,558,182 control/non-ovarian cancer participants). Higher dietary intakes of total fat (RR = 1.19, 95% CI = 1.06-1.33, I2 = 60.3%), cholesterol (RR = 1.14, 95% CI = 1.03-1.26, I2 = 19.4%), saturated fat (RR = 1.13, 95% CI = 1.04-1.22, I2 = 13.4%), and animal fat (RR = 1.21, 95% CI = 1.01-1.43, I2 = 70.5%) were significantly associated with a higher risk of ovarian cancer. A higher level of serum triglycerides was accompanied by a higher risk of ovarian cancer (RR = 1.33, 95% CI = 1.02-1.72, I2 = 89.3%). This meta-analysis indicated that a higher daily intake of total fat, saturated fat, animal fat, and cholesterol and higher levels of serum triglycerides were significantly associated with an increased risk of ovarian cancer.
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BACKGROUND: There is epidemiological evidence which suggests an association between 25-hydroxyvitamin D [25(OH)D] levels and bone and muscle function; however, it is unclear whether vitamin D supplementation has an added benefit beyond bone health. Here, we investigated the effects of vitamin D3 supplementation (1 month) on physical performance in Chinese university students in winter. METHODS: One hundred and seventeen eligible subjects with 25(OH)D (19.2 ± 7.8 ng/mL) were randomly assigned to either vitamin D3 supplement (N = 56; 1000 IU/day) or the control (N = 61) group for 1 month. Pre- and post-measurements included: 1) serum levels of 25(OH)D; 2) musculoskeletal and pulmonary function [vertical jump height (VJH) and right handgrip strength (RHS), forced vital capacity (FVC), and forced expiratory volume at 1s (FEV1)]; 3) bone turnover markers [parathyroid hormone (PTH), n-terminal osteocalcin (N-MID), and calcium]; 4) hemoglobin-related parameters [hemoglobin (Hb), hematocrit (HCT), red blood cells (RBC), and red cell distribution width (RDW)]; 5) lipid parameters [total triglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C)]; 6) Fatigue-related indicators [serum creatine kinase (CK), lactate dehydrogenase (LDH), and total testosterone (T)]. In addition, aerobic capacity was assessed by measuring maximal oxygen uptake (VO2max) at baseline. RESULTS: During wintertime, supplementation with 1000 IU/d of vitamin D3 significantly increased serum 25(OH)D levels (from 18.85 ± 7.04 to 26.98 ± 5.88 ng/mL, p < 0.05), accompanied by a decrease of PTH (p < 0.05). However, vitamin D3 supplementation did not significantly impact the physical performance, serum lipid parameters, and bone turnover markers of students. Furthermore, 25(OH)D was found to be positively correlated with VJH and negatively correlated with PTH and TC at the beginning and end of the study (p < 0.05). In addition, the multiple linear regression analysis showed that 25(OH)D combined with athletic, gender, height, weight, Hb, and FVC could account for 84.0% of the VO2max value. CONCLUSIONS: The study demonstrated that one-month of 1000 IU/d of vitamin D3 supplementation during the winter had beneficial effects on 25(OH)D status and PTH. However, vitamin D3 intervention was not sufficient to improve physical performance. Furthermore, 25(OH)D levels combined with athletic, Hb and FVC could be a predictor of VO2max.