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1.
Clin Res Hepatol Gastroenterol ; : 101812, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34597849

RESUMO

BACKGROUND: Transglutaminase 3 (TGM3) regulates multiple oncogene pathways (GSK-3ß/ß-catenin pathway, Akt/ERK pathway, etc.) to promote hepatocellular carcinoma (HCC) cell proliferation, migration and invasion, however, its clinical value for HCC management is still limited. Therefore, we conducted this study to compare the TGM3 expression between tumor tissue and paired adjacent noncancerous tissue, aiming to explore the clinical application of TGM3 in HCC patients. METHODS: Totally, 208 HCC patients were enrolled and their clinicopathological features were collected. Then, 208 pairs of HCC specimens and adjacent noncancerous specimens were used to detect TGM3 protein expression by IHC assay and assessed by a semi-quantitative scoring method. Besides, 157 pairs were proposed to detect TGM3 mRNA expression by RT-qPCR. RESULTS: Both TGM3 protein (P<0.001) and mRNA (P<0.001) levels were increased in HCC specimens compared to adjacent noncancerous specimens. Besides, TGM3 high protein expression correlated with multifocal tumor nodules (P<0.001), advanced Barcelona Clinic Liver Cancer (BCLC) stage (P=0.006), higher carcinoembryonic antigen (P=0.038) and alpha-fetoprotein (AFP) (P<0.001). While TGM3 high mRNA expression correlated with multifocal tumor nodules (P=0.025), largest tumor size ≥ 5.0 cm (P=0.042) and higher AFP (P=0.019). Furthermore, both TGM3 protein (P=0.002) and mRNA (P=0.028) high expressions correlated with shorter overall survival (OS). While after adjustment by multivariant Cox's regression, TGM3 protein high expression (vs. low) independently predicted worse OS (P=0.004). CONCLUSIONS: TMG3 expression is increased in tumor tissue, also its high expression correlates with multiple tumor nodules, higher BCLC stage, abnormal AFP and reduced OS in HCC patients.

2.
Clin Res Hepatol Gastroenterol ; : 101796, 2021 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-34500119

RESUMO

BACKGROUND: Chaperonin-containing tailless complex polypeptide 1 subunit 6A (CCT6A) plays roles in cancer progression, but its clinical implication in hepatocellular carcinoma (HCC) management needs further exploration. This study aimed to explore the correlation of CCT6A with clinical characteristics, liver function indexes, tumor markers and prognosis in HCC patients. METHODS: 240 HCC patients were retrospectively enrolled. 240 pairs of cancer and adjacent specimens were used to evaluate CCT6A protein expression by immunohistochemistry assay; among which 184 pairs were used to assess CCT6A mRNA expression by reverse transcription-quantitative polymerase chain reaction. RESULTS: Both CCT6A protein expression and CCT6A mRNA expression were higher in HCC tumor tissue than in adjacent tissue (P<0.001). The receiver operating characteristic (ROC) curve showed that CCT6A had certain potential in discriminating tumor tissues from adjacent tissues. In addition, CCT6A protein expression was positively correlated with multifocal tumor nodule (P=0.001), ≥5.0 cm tumor size (P=0.028), BCLC stage (P=0.002) and abnormal AFP (P=0.021). Besides, CCT6A mRNA expression was associated with multifocal tumor nodule (P=0.025), ≥5.0 cm tumor size (P=0.018), higher BCLC stage (P=0.036), abnormal CA199 (P=0.027) and abnormal AFP (P=0.008). However, no correlation was found in CCT6A with liver function indexes (all P>0.05). Moreover, CCT6A protein and mRNA high expressions were both correlated with poor accumulating overall survival (OS) (P=0.004, P=0.002, respectively). Furthermore, CCT6A protein high expression (vs. low) independently predicted shorter OS (P=0.027). CONCLUSIONS: CCT6A serves as a possible biomarker reflecting tumor features and prognostication in HCC patients.

3.
Adv Sci (Weinh) ; 8(19): e2101727, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34382356

RESUMO

Solar vapor generation technology is promising in seawater desalination, sewage purification, and other fields. However, wide application of this technology is still largely confined due to its high cost and difficulties for scalable production. In this study, an ever-floating solar evaporator is fabricated by coating multiwall carbon nanotubes on a bicomponent nonwoven composed of polypropylene/polyethylene core-sheath fibers. This all-fiber structure is highly porous and ultralight, with large specific area (for efficient water evaporation), interconnected channels (for easy vapor escape), and low thermal conductivity (to avoid heat loss). The unique unidirectional water-transfer behavior of the nonwoven enables it to spontaneously pump an adjustable amount of water for interfacial solar heating and a delicate balance between water supply and loss may accelerate the evaporation speed of water. These distinct benefits endow the solar evaporator with excellent evaporation rates of 1.44 kg m-2  h-1 under the simulated irradiation of 1 sun and 12.81 kg m-2  d-1 under natural sunlight. Moreover, the evaporator can be fabricated by using low-cost materials and industrialized methods (overall cost ≈2.4 USD m-2 ), making one believe its practical significance for commercial solar steam evaporation.

4.
Psychoneuroendocrinology ; 133: 105388, 2021 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-34450359

RESUMO

Self-regulation is theoretically closely related to coping with stressful events, yet whether self-regulation capacities can predict individual stress responses is largely unknown. Cognitive control and emotion regulation are two major aspects involved in self-regulation, both of which are mechanisms to support goal-directed behaviors. Here, we aimed to elucidate whether the neural processes involved in emotion regulation and cognitive control could predict the cortisol response to stress. Therefore, we recorded first electroencephalography (EEG) during a cognitive conflict task (Simon task) and an emotion regulation task (cognitive reappraisal and expressive suppression) before healthy participants (n = 72) underwent a psychosocial stressor. Our results showed that late positive potentials (LPPs) during the emotion regulation task predicted both cortisol reactivity to and recovery from stress. Cognitive control and its neural underpinning, however, did not predict the individual stress response. These findings indicate that neural emotion regulation processes can predict HPA axis response to stress, and suggest a differential involvement of cognitive and affective components of self-regulation in the adaptation to stressful events.

5.
Talanta ; 234: 122701, 2021 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-34364498

RESUMO

Conventional methods for the detection of the sulfur mustard poisoning metabolic marker, thiodiglycol (TDG), require expensive instruments and reagents as well as professional operators. To address these problems, a novel test strip based on a molecularly imprinted sensitive membrane (MIM) was developed in this work for point-of-care (POC) detection of TDG. The TDG test strip was prepared conveniently by coating molecular imprinted polymers (MIPs) on a nitrocellulose membrane. When the sample contained TDG, the MIPs could specifically bind with TDG. A great number of AuNPs (AuNPs) could then be adsorbed on the test strip via the formation of an Au-S bond between TDG and AuNPs, giving the test strip the obvious red color of AuNPs. In the absence of TDG, the test strip exhibited much lighter color because it could not adsorb AuNPs. By monitoring the color change of the test strip, TDG could be detected from 1.0 ng/mL to 100.0 µg/mL with a detection limit of 0.23 ng/mL (3σ) under the optimal conditions (the molar ratio of TDG to MAA was 1:2; the eluent was chloroform; the elution time was 50 min; the reaction time between MIPs and TDG was 15 min; the adsorption time of AuNPs was 40 min; the temperature of the reaction system was 35 °C). This method has excellent selectivity and has been used to detect TDG in urine, showing great potential for POC detection of TDG in clinical samples.


Assuntos
Nanopartículas Metálicas , Impressão Molecular , Gás de Mostarda , Cromatografia Gasosa-Espectrometria de Massas , Ouro , Sistemas Automatizados de Assistência Junto ao Leito , Compostos de Sulfidrila
6.
Yonsei Med J ; 62(8): 691-701, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34296546

RESUMO

PURPOSE: Resveratrol (REV), a natural compound found in red wine, exhibits antitumor activity in various cancers, including ovarian cancer (OC). However, its potential anti-tumor mechanisms in OC are not well characterized. Here, we tried to elucidate the underlying mechanisms of REV in OC cells. MATERIALS AND METHODS: The anti-proliferative effects of REV against OC cells were measured using CCK-8 assay. Apoptosis was measured using an Annexin V-FITC/PI apoptosis detection kit. The anti-metastasis effects of REV were evaluated by invasion assay and wound healing assay. The miRNA profiles in REV-treated cells were determined by microarray assay. RESULTS: Our results showed that REV treatment suppresses the proliferation, induces the apoptosis, and inhibits the invasion and migration of OV-90 and SKOV-3 cells. miR-34a was selected for further study due to its tumor suppressive roles in various human cancers. We found miR-34a overexpression enhanced the inhibitory effects of REV on OC cells, whereas miR-34a inhibition had the opposite effect in OC cells. In addition, we verified that BCL2, an anti-apoptotic gene, was found directly targeted by miR-34a. We also found that REV reduced the expression of Bcl-2 in OC cells. Further investigations revealed that overexpression of Bcl-2 significantly abolished the anti-tumor effects of REV on OC cells. CONCLUSION: Overall, these results demonstrated that REV exerts anti-cancer effects on OC cells through an miR-34a/Bcl-2 axis, highlighting the therapeutic potential of REV for treatment of OC.


Assuntos
MicroRNAs , Neoplasias Ovarianas , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Resveratrol/farmacologia , Regulação para Cima
7.
Int J Mol Med ; 48(3)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34278450

RESUMO

Endometrial cancer (EC) is widely known as an aggressive malignancy. Due to the limited therapeutic options and poor prognosis of patients with advanced­stage EC, there is a need to identify effective alternative treatments. Chrysin is a naturally active flavonoid (5,7­dihydroxyflavone), which has been demonstrated to exert anticancer effects and may present a novel strategy for EC treatment. However, the role of chrysin in EC remains largely unclear. The aim of the present study was to examine the anticancer effects of chrysin on EC. The results revealed that, in addition to apoptosis, chrysin increased the LC3II expression levels and markedly accelerated the autophagic flux, suggesting that chrysin induced both the autophagy and apoptosis of EC cells. Furthermore, the inhibition of autophagy by chloroquine enhanced the inhibitory effect on cell proliferation and the promotion of the chrysin­induced apoptosis of EC cells, indicating that chrysin­induced autophagy was a cytoprotective mechanism. Additionally, chrysin led to the production of intracellular reactive oxygen species (ROS). N­acetylcysteine (NAC) pretreatment significantly inhibited chrysin­induced autophagy, suggesting that ROS activated autophagy induced by chrysin in EC cells. Furthermore, the phosphorylated (p­)Akt and p­mTOR levels were significantly decreased in a concentration­dependent manner following treatment with chrysin, while NAC blocked these effects. Taken together, these findings demonstrated that chrysin­induced autophagy via the inactivation of the ROS­mediated Akt/mTOR signaling pathway in EC cells.

8.
Anal Methods ; 13(12): 1489-1494, 2021 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-33690735

RESUMO

In this work, homo-FRET (Förster resonance energy transfer between the same kind of fluorophores) takes place in a hetero-FRET (FRET between two different fluorophores) system and can effectively improve the energy transfer efficiency. Herein, a novel ratiometric fluorescence method was developed for the detection of nuclease activity. Exonuclease III (Exo III), an enzyme which has a high exodeoxyribonuclease activity for double-stranded DNA (dsDNA) in the 3' to 5' direction, was chosen as a proof of concept of this strategy. In a linear dsDNA template, the occurrence of homo-FRET in two Cy3 donors enables the highly efficient transfer of energy to the Cy5 acceptor. The ratio of fluorescence intensity between Cy3 and Cy5 (FD/FA) increases in an Exo III concentration-dependent manner, which built the foundation of Exo III quantification. This method exhibits a linear range from 0.25 to 8 U mL-1 with a detection limit of 0.17 U mL-1. Importantly, this platform also shows the potential for screening Exo III inhibitors and detecting Exo III activity in complex samples.


Assuntos
Exodesoxirribonucleases , Transferência Ressonante de Energia de Fluorescência , Exodesoxirribonucleases/metabolismo , Corantes Fluorescentes , Espectrometria de Fluorescência
9.
J Int Med Res ; 49(3): 300060521997718, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33752504

RESUMO

OBJECTIVE: C-X-C motif chemokine ligand 5 (CXCL5), a member of the chemokine family, is associated with remodeling of connective tissues. However, its role in formation of intrauterine adhesions (IUA) remains unclear. We aimed to investigate the expression and mechanism underlying the role of CXCL5 in IUA. METHODS: Expression of CXCL5 in IUA was detected by immunohistochemistry in a rat model of IUA and by real-time PCR and western blotting in patients with IUA. The protein levels of matrix metalloproteinase 9 (MMP9) and transcription factor p65 in human endometrial cells were assessed by western blotting after CXCL5 overexpression. RESULTS: Protein expression of CXCL5 was significantly decreased in the endometria of IUA rats compared with that of control and sham-operated rats. Real-time PCR and western blotting in patients with IUA showed similar results to those from the rat model. After overexpression, CXCL5 significantly upregulated expression of MMP9 and slightly upregulated expression of p65 in human endometrial cells. CONCLUSIONS: CXCL5 plays an important role in IUA formation after endometrial injury. We propose a molecular mechanism to explain formation of IUA, including downregulation of MMP9 by low CXCL5 expression. These findings provide valuable information for the prevention and targeted therapy of IUA.


Assuntos
Doenças Uterinas , Animais , Quimiocina CXCL5/genética , Endométrio/patologia , Feminino , Humanos , Imuno-Histoquímica , Metaloproteinase 9 da Matriz/genética , Ratos , Aderências Teciduais/patologia , Doenças Uterinas/patologia
10.
Oncol Rep ; 45(2): 787-788, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33416110

RESUMO

Following the publication of the above paper, an interested reader drew to our attention apparent anomalies associated with Figs. 2, 3 and 4; essentially, these three figures contained panels exhibiting overlapping data, such that data purportedly relating to different experiments were apparently drawn from the same original sources. [Specifically, the Ski, +TGF­ß1 data panel in Fig. 2B, the Mock, +TGF­ß1 data panel in Fig. 3A, and the +TGF­ß1, +SIS3 data panel in Fig. 4B in the original figures were chosen incorrectly.] Upon investigating this matter with the authors, the authors have realized that they made errors in the compilation of the affected figures. The errors were made inadvertently, and the authors have been able to identify the correct data for each of the figures concerned. The corrected versions of these figures are shown opposite and on the next page. Note that these errors did not affect the overall conclusions reported in the study. The authors are grateful to the Editor of Oncology Reports for allowing them the opportunity to publish this Corrigendum; furthermore, the authors apologize for any inconvenience caused to the readership of the Journal. [the original article was published in Oncology Reports 34: 87-94, 2015; DOI: 10.3892/or.2015.3961].

11.
J Cell Physiol ; 236(1): 6-14, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32506425

RESUMO

Endometriosis refers to a benign chronic gynecological disorder, and is defined as the ectopic growth of endometrium in pelvic cavity. Endometriosis affects about 10% of reproductive-aged women. Unfortunately, the pathogenesis of endometriosis remains obscure, and the disease witnesses a lack of effective therapy approaches. Therefore, more research needs to be performed to throw light on endometriosis, its pathogenesis, and therapy. Long noncoding RNAs (lncRNAs), which are defined as functional cellular RNA longer than 200 nucleotides, have been implicated in many chronic disorders. It has been suggested that lncRNAs are closely related to the endometriosis process. Nevertheless, the molecular mechanisms by which lncRNAs associate with endometriosis should be elucidated more detailed. In our brief review, we first exhibit the aberrant lncRNAs expression in endometriosis. Then, we talk about the molecular mechanisms underlying lncRNAs in endometriosis. Finally, we also present the potential of lncRNAs as biomarkers for endometriosis.


Assuntos
Endometriose/genética , RNA Longo não Codificante/genética , Animais , Biomarcadores/metabolismo , Endometriose/patologia , Endométrio/metabolismo , Endométrio/patologia , Feminino , Expressão Gênica/genética , Humanos
12.
J Strength Cond Res ; 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33306593

RESUMO

Teng, Y, Yu, Q, Yu, X, Zhan, L, and Wang, K. Neuropsychological study on the effects of boxing upon athletes' memory. J Strength Cond Res XX(X): 000-000, 2020-This study attempts to explore the impairment of athletes' memory caused by 1 year of boxing training according to the n-back test and Chinese auditory learning test (CALT). Accordingly, 58 new athletes were prospectively analyzed from a sports school, where 28 athletes who received boxing training were regarded as the exposed group and 30 athletes who received matched training were taken as unexposed group for a duration of 1 year. All participants respectively completed an n-back test (to test working memory) and a CALT test (to test short-term memory and long-term memory) before and after the training. During the tests, accuracy and reaction time from the n-back test and the correct number from CALT were recorded. The accuracy of the boxing group was observed to be lower than that of the matched group in the 2-back test (p < 0.05), whereas the reaction time of the boxing group was longer than that of the matched group (p < 0.05) after a year of boxing practice. The results of CALT1 (short-term memory), CALT8 (long-term memory), and CALT9 (recognition memory) were lower in the boxing group than that in the matched group after a year (p < 0.05). The results suggest that exposure to 1 year of boxing training can impair the boxers' working memory, short-term memory, and long-term memory. Therefore, boxers should strengthen their head protection during training to avoid frequent impacts to the head.

13.
Oncol Rep ; 44(5): 1787-1798, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000238

RESUMO

Cervical, ovarian and endometrial cancer are the three most common types of malignant tumor and the leading causes of cancer­associated death in women. Tumor debulking surgery followed by platinum and paclitaxel chemotherapy is the current treatment regime of choice. However, as a result of late diagnosis and chemoresistance, the survival rates of patients with advanced gynecological cancers remains unsatisfactory. Circular RNAs (circRNAs) are stable noncoding RNAs that are present in a wide variety of tissue and cell types. With the enhancement of RNA sequencing methods, increasing numbers of circRNAs have been identified, and their functions are gradually being revealed. In recent years, circRNAs have received increasing attention for their regulatory roles in cervical, ovarian and endometrial cancer. The aim of the present review was to summarize the possible mechanisms of recently identified circRNAs; we hypothesize that a novel diagnostic and therapeutic biomarker may be identified to prolong the survival time of patients with gynecological malignancies.

14.
Front Pharmacol ; 11: 1281, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33013364

RESUMO

Nod-like receptor (NLR) family caspase activation and recruitment domain containing 5 (NLRC5) is a newly identified sub-class of the NLR family. It regulates inflammation and has a key function in innate and adaptive immunologic reactions. Autophagy has been reported to be crucially linked to the pathogenesis of endometriosis. Our recent study identify there is a negative correlation between NLRC5 and autophagy in endometriosis, indicating that NLRC5 and autophagy together act as promising predictors in endometriosis patients. However, the mechanism associating NLRC5 and autophagy in endometriosis is still not completely understood. We hypothesize that autophagy could be involved in NLRC5-mediated inflammation in endometriosis. In order to validate the assumption, we evaluate the effects of NLRC5 and autophagy in the inflammation of ectopic endometrial stromal cells (EESCs) of ovarian endometriosis patients, to specifically determine whether autophagy is involved in NLRC5-mediated inflammation in EESCs. Our results show that over-expression of NLRC5 results in the up-regulation of autophagy in EESCs and inhibition of NLRC5 restricts the level of autophagy in EESCs. Furthermore, over-expression of NLRC5 and promotion of autophagy inhibit interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) expressions, whereas inhibition of NLRC5 and autophagy up-regulate IL-6 and TNF-α expressions in EESCs. Additionally, promotion of autophagy contributes to the NLRC5-mediated inhibition of IL-6 and TNF-α expressions in EESCs; inhibition of autophagy restricts NLRC5-mediated inhibition of IL-6 and TNF-α expressions in EESCs. Our results suggest that over-expression of NLRC5 promotes autophagy, thereby inhibiting inflammation in ovarian endometriosis.

15.
Curr Med Sci ; 40(5): 998, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33123914

RESUMO

It is hereby certified that there is no shared co-first authorship in this paper. Dr. Nan HUANG is the only first author of this article.

16.
Life Sci ; 261: 118358, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32866518

RESUMO

Preeclampsia (PE) is a pregnancy-specific disorder characterized by the onset of hypertension and proteinuria with onset after the 20th week of gestation. The pathogenesis of PE is attributed to increased trophoblast cell death and poor trophoblast migration/invasiveness. This study investigates the function of microRNA-23a (miR-23a) in PE and its effects on migration and invasion of trophoblast cells HTR-8/SVneo. We found higher expression of miR-23a in placental tissue samples from PE pregnant women compared to samples from normal pregnant women. Enhancing miR-23a expression by its specific mimic reduced HTR-8/SVneo cell migration and invasion and increased HTR-8/SVneo cell apoptosis. The dual-luciferase reporter gene assay revealed miR-23a binding with HDAC2. We found that HDAC2 was poorly expressed in placental tissue samples from PE pregnant women, and its expression correlated inversely with miR-23a expression. HTR-8/SVneo cells showed diminished HDAC2 expression upon miR-23a elevation and increased HDAC2 expression upon miR-23a inhibition. Lentivirus-mediated HDAC2 knockdown mimicked the effects of miR-23a on HTR-8/SVneo cells and led to NF-κB activation. Similarly, HDAC2 overexpression and NF-κB inhibition both abrogated the effects of miR-23a on HTR-8/SVneo cells, suggesting that miR-23a reduced HTR-8/SVneo cell migration and invasion and increased HTR-8/SVneo cell apoptosis by HDAC2 inhibition and NF-κB activation. In summary, these results support a novel role of miR-23b in invasion and apoptosis of trophoblast cells, and imply that targeting miR-23b may be a new avenue for treating PE.


Assuntos
Movimento Celular/genética , Histona Desacetilase 2/metabolismo , NF-kappa B/metabolismo , Trofoblastos/citologia , Trofoblastos/metabolismo , Adulto , Sequência de Bases , Linhagem Celular , Regulação para Baixo/genética , Feminino , Humanos , Lentivirus/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Modelos Biológicos , Transdução de Sinais , Regulação para Cima/genética
17.
Oncol Lett ; 20(5): 162, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32934730

RESUMO

Sirtuin 3 (Sirt3) is an important member of the sirtuin protein family. It is a deacetylase that was previously reported to modulate the level of reactive oxygen species (ROS) production and limit the extent of oxidative damage in cellular components. As an important member of the class III type of histone deacetylases, Sirt3 has also been documented to mediate nuclear gene expression, metabolic control, neuroprotection, cell cycle and proliferation. In ovarian cancer (OC), Sirt3 has been reported to regulate cellular metabolism, apoptosis and autophagy. Sirt3 can regulate autophagy through a variety of different molecular signaling pathways, including the p62, 5'AMP-activated protein kinase and mitochondrial ROS-superoxide dismutase pathways. However, autophagy downstream of Sirt3 and its association with OC remains poorly understood. In the present review, the known characteristics of Sirt3 and autophagy were outlined, and their potential functional roles were discussed. Following a comprehensive analysis of the current literature, Sirt3 and autophagy may either serve positive or negative roles in the regulation of OC. Therefore, it is important to identify the appropriate expression level of Sirt3 to control the activation of autophagy in OC cells. This strategy may prove to be a novel therapeutic method to reduce the mortality of patients with OC. Finally, potential research directions into the association between Sirt3 and other signaling pathways were provided.

18.
Stroke ; 51(10): 2997-3006, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32951540

RESUMO

BACKGROUND AND PURPOSE: Symptomatic hemorrhage contributes to an increased risk of repeated bleeding and morbidity in cerebral cavernous malformation (CCM). A better understanding of morbidity after CCM hemorrhage would be helpful to identify patients of higher risk for unfavorable outcome and tailor individualized management. METHODS: We identified 282 consecutive patients who referred to our institute from 2014 to 2018 for CCM with symptomatic hemorrhage and had an untreated follow-up period over 6 months after the first hemorrhage. The morbidity after hemorrhage was described in CCM of different features. Nomogram to predict morbidity was formulated based on the multivariable model of risk factors. The predictive accuracy and discriminative ability of nomogram were determined with concordance index (C-index) and calibration curve, and further validated in an independent CCM cohort of a prospective multicenter study from 2019 to 2020. RESULTS: The overall morbidity of CCM was 26.2% after a mean follow-up of 1.9 years (range 0.5-3.5 years) since the first hemorrhage. The morbidity during untreated follow-up was associated with hemorrhage ictus (adjusted odds ratio per ictus increase, 4.17 [95% CI, 1.86-9.33]), modified Rankin Scale score at initial hemorrhage (adjusted odds ratio per point increase, 2.57 [95% CI, 1.82-3.63]), brainstem location (adjusted odds ratio, 2.93 [95% CI, 1.28-6.68]), and associated developmental venous anomaly (adjusted odds ratio, 2.21 [95% CI, 1.01-4.83]). Subgroup analysis revealed similar findings in brainstem and non-brainstem CCM. Nomogram was contracted based on these features. The calibration curve showed good agreement between nomogram prediction and actual observation. The C-index of nomogram predicting morbidity was 0.83 (95% CI, 0.77-0.88). In validation cohort, the nomogram maintained the discriminative ability (C-index, 0.87 [95% CI, 0.78-0.96]). CONCLUSIONS: Multiple symptomatic hemorrhages, initial neurological function after hemorrhage, brainstem location, and associated developmental venous anomaly were associated with morbidity of CCM hemorrhage. The nomogram represented a practical approach to provide individualized risk assessment for CCM patients. Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT04076449.


Assuntos
Hemangioma Cavernoso do Sistema Nervoso Central/complicações , Hemorragias Intracranianas/etiologia , Adulto , Feminino , Seguimentos , Hemangioma Cavernoso do Sistema Nervoso Central/diagnóstico por imagem , Humanos , Hemorragias Intracranianas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Nomogramas , Recidiva , Medição de Risco , Fatores de Risco , Adulto Jovem
19.
Oncol Lett ; 20(3): 2075-2090, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32782525

RESUMO

Immunotherapy is an emerging clinical approach that has gained traction over the past decade as a novel treatment option for lung cancer and melanoma. Notably, researchers have made marked improvements in the treatment of endometrial cancer (EC), and potential immune responses have been identified in patients with EC, thereby offering the possibility of exploring immunotherapy for EC. Nevertheless, various needs remain unmet, and immunotherapy applications in EC have yielded limited success, as only a minority of patients exhibited a clinical response. Therefore, further understanding of immune dysfunction associated with EC is still required. The present review describes recent findings regarding the immunosuppressive microenvironment of EC, with emphasis on immune evasion mechanisms and immunotherapy in EC.

20.
Onco Targets Ther ; 13: 7851-7864, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32821126

RESUMO

Purpose: Colorectal cancer cells spread to the liver and crosstalk with the microenvironment, and hepatic stellate cells (HSCs) are the major stromal components in the liver. However, the role of the interaction between colorectal tumor cells and HSCs in chemotherapeutic resistance remains unclear. The present study aimed to determine the mechanism of colorectal tumor cells educating the HSCs to reprogram the metabolism of adjacent tumor cells and fuel themselves in the metastatic microenvironment of the liver. Patients and Methods: Immunohistochemistry (IHC) examined the expression of the monocarboxylate transporters 1 (MCT1) and lactate dehydrogenase B (LDHB) in colorectal liver metastases (CRLM). The Mann-Whitney U-tests analyzed the association between IL-6 levels and clinical parameters. The mechanisms of normoxic tumor-derived exosomes in the education of HSCs were investigated using IHC and ELISA. The conditioned medium of activated HSCs in the regulation of hypoxic tumor cells was analyzed by CCK-8 and cell apoptosis assays. Results: The expression of MCT1 and LDHB was high in the liver metastases of irinotecan-resistant patients, and the high level of IL-6 in the plasma of patients with CRLM was associated with poor response to irinotecan-based chemotherapy. The colorectal tumor-derived exosomes activated HSCs to secrete excessive IL-6. Furthermore, the conditioned medium of activated HSCs enhanced the lactate metabolism of hypoxic tumor cells by activating the IL-6/STAT3 pathway and upregulating the downstream MCT1 and LDHB, in order to confer the resistance of SN38, which is the active metabolite of irinotecan. Conclusion: Taken together, the cultured supernatant of normoxic exosome-educated HSCs enhances the lactate metabolism of hypoxic tumor cells via the IL-6/STAT3 pathway, in order to confer the SN38 resistance in a mimic liver metastatic microenvironment.

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