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1.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(4): 521-530, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34494521

RESUMO

Objective To quantitatively evaluate the associations of PM2.5,PM10,NO2,and SO2 concentrations with the outpatient visits for atopic dermatitis in Lanzhou. Methods The data of outpatient visits,together with meteorological data and air pollutant data,from January 2013 to December 2017 were collected.The generalized additive model based on Poisson distribution was employed to study the lag effects of PM2.5,PM10,NO2,and SO2 concentrations on the visits of outpatients,with the seasonal and long-term trends and day-of-the-week effect controlled. Results The results of the single pollutant model showed that PM2.5 and PM10 had the most obvious while still insignificant impact on the outpatient visits for atopic dermatitis on the current day(lag0).NO2 also had the most obvious impact in the case of lag0 and showed a lag effect.For each 10 µg/m3 increase in NO2 concentration,the excess risk(ER)of outpatient visits for atopic dermatitis was 1.95%(95% CI=1.09%-2.82%,P=0.01).SO2 had the most significant effect on lag6,and the outpatient visits increased by 1.55%(95% CI=0.48%-2.54%)for every 10 µg/m3 rise in SO2 concentration(P=0.02).Females were more sensitive to PM10 and SO2 than males.For every 10 µg/m3 increase in PM10 and SO2,the female outpatient visits increased by 0.02% and 2.47%,respectively.Males were sensitive to PM2.5 and NO2,and the every 10 µg/m3 rise in PM2.5 and NO2 increased male outpatient visits by 0.47% and 1.78%,respectively.Gaseous pollutants(NO2 and SO2)had more significant effect on people ≤2 years old than on those of other ages.Every 10 µg/m3 rise in NO2 and SO2 would increase the ≤2-year-old outpatient visits by 2.35% and 1.57%,respectively(P=0.02).People of 13-59 years old were sensitive to NO2 concentration,and every 10 µg/m3 rise in NO2 concentration increased their visits by 1.39%.NO2 affected the outpatient visits during the cold and warm seasons,with the ER values of 2.35% and 1.89%,respectively(P=0.01).Particulate matter(PM2.5 and PM10)had the most obvious yet insignificant association with the outpatient visits in winter.The interactions between PM2.5 and NO2,between PM10 and NO2,and between SO2 and NO2 affected the total outpatient visits for atopic dermatitis.The results of double pollutant model showed that in the presence of PM2.5,PM10,or SO2,the effect of NO2 on the outpatient visits for atopic dermatitis enhanced compared with that predicted by single pollutant model(P=0.01). Conclusion The air pollutants(PM2.5,PM10,NO2,and SO2)in Lanzhou were closely related to the outpatient visits for atopic dermatitis,and the increased concentrations of NO2 and SO2 was more likely to increase the risk of atopic dermatitis.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Dermatite Atópica , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Pré-Escolar , China , Dermatite Atópica/epidemiologia , Feminino , Humanos , Masculino , Pacientes Ambulatoriais , Material Particulado/efeitos adversos , Material Particulado/análise
2.
J Transl Med ; 19(1): 347, 2021 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-34389031

RESUMO

BACKGROUND: Tumor-associated macrophages (TAM) are immunosuppressive cells that contribute to impaired anti-cancer immunity. Iron plays a critical role in regulating macrophage function. However, it is still elusive whether it can drive the functional polarization of macrophages in the context of cancer and how tumor cells affect the iron-handing properties of TAM. In this study, using hepatocellular carcinoma (HCC) as a study model, we aimed to explore the effect and mechanism of reduced ferrous iron in TAM. METHODS: TAM from HCC patients and mouse HCC tissues were collected to analyze the level of ferrous iron. Quantitative real-time PCR was used to assess M1 or M2 signature genes of macrophages treated with iron chelators. A co-culture system was established to explore the iron competition between macrophages and HCC cells. Flow cytometry analysis was performed to determine the holo-transferrin uptake of macrophages. HCC samples from The Cancer Genome Atlas (TCGA) were enrolled to evaluate the prognostic value of transferrin receptor (TFRC) and its relevance to tumor-infiltrating M2 macrophages. RESULTS: We revealed that ferrous iron in M2-like TAM is lower than that in M1-like TAM. In vitro analysis showed that loss of iron-induced immunosuppressive M2 polarization of mouse macrophages. Further experiments showed that TFRC, the primary receptor for transferrin-mediated iron uptake, was overexpressed on HCC cells but not TAM. Mechanistically, HCC cells competed with macrophages for iron to upregulate the expression of M2-related genes via induction of HIF-1α, thus contributing to M2-like TAM polarization. We further clarified the oncogenic role of TFRC in HCC patients by TCGA. TFRC is significantly increased in varieties of malignancies, including HCC, and HCC patients with high TFRC levels have considerably shortened overall survival. Also, TFRC is shown to be positively related to tumor-infiltrating M2 macrophages. CONCLUSIONS: Collectively, we identified iron starvation through TFRC-mediated iron competition drives functional immunosuppressive polarization of TAM, providing new insight into the interconnection between iron metabolism and tumor immunity.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Linhagem Celular Tumoral , Humanos , Ferro , Camundongos , Macrófagos Associados a Tumor
3.
Org Lett ; 23(15): 5626-5630, 2021 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-34269061

RESUMO

Aryl bromide is one of the most important compounds in organic chemistry, because it is widely used as synthetic building blocks enabling quick access to a wide array of bioactive molecules, organic materials, and polymers via the versatile cutting-edge transformations of C-Br bond. Direct C-H bond functionalization of aryl bromide is considered to be an efficient way to prepare functionalized aryl bromides; however, it is rarely explored possibly due to the relatively low reactivity of aryl bromide toward C-H bond activation. We herein report a palladium-catalyzed coupling reaction between aryl iodide and aryl bromide for preparing brominated biaryl compounds via a silver-mediated C-H bond activation pathway.

4.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 43(2): 180-187, 2021 Apr 28.
Artigo em Chinês | MEDLINE | ID: mdl-33966695

RESUMO

Objective To determine the relationship between air pollutants [SO2,NO2,8 hours average concentration of ozone(O38h)] and outpatient visits for acne in Lanzhou,China. Methods Data of daily outpatient visits for acne and concentrations of air pollutants(SO2,NO2,and O38h)from January 2013 to December 2017 were collected.With the control of long-term trend and day-of-week effect,a distributed lag nonlinear model was used to analyze the lag and cumulative effects of air pollutants on the outpatient visits.The model was established based on the different groups of gender and age. Results During the study period,the average daily outpatient visits were 34.94±15.27,and the average concentrations of SO2,NO2,and O38h were 24.09,43.77,and 82.94 µg/m3,respectively.The Spearman's correlation analysis showed that the daily outpatient visits for acne were positively correlated with NO2 concentration while negatively correlated with O38h concentration;SO2 concentration was negatively correlated with O38h concentration;NO2 concentration was positively correlated with SO2 and O38h concentrations.A 10 µg/m3 increase in daily concentrations of NO2 and SO2 was respectively associated with 2.61%(95% CI=0.98%-4.27%)and 1.71%(95% CI=0.54%-2.89%)increase in the outpatient visits for acne.A 10 µg/m3 increase in O38h concentration was associated with -0.62%(95% CI=-1.12%--0.11%)increase in the outpatient visits.Multipollutant models indicated that air pollutant concentrations were significantly associated with the daily outpatient visits for acne. Conclusions SO2 and NO2 are positively associated with daily dermatological department visits for acne in Lanzhou,while O38h concentration has a negative correlation with the visits.The sensitivity of acne daily outpatient visits to changes in SO2,NO2,and O38h varies among patients of different genders and at different ages.


Assuntos
Acne Vulgar , Poluição do Ar , Poluentes Ambientais , Poluição do Ar/efeitos adversos , China/epidemiologia , Feminino , Gases , Humanos , Masculino , Pacientes Ambulatoriais
5.
Org Lett ; 23(5): 1554-1560, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33586989

RESUMO

Deterium-labeled (hetero)aryl bromide is one of the most widespread applicable motifs to achieve important deuterated architectures for various scientific applications. Traditionally, these deterium-labeled (hetero)aryl bromides are commonly prepared via multistep syntheses. Herein, we disclose a direct H/D exchange protocol for deuteration of (hetero)aryl bromides using Ag2CO3 as catalyst and D2O as deuterium source. This protocol is highly efficient, simply manipulated, and appliable for deuterium-labeling of over 55 (hetero)aryl bromides including bioactive druglike molecules and key intermediates of functional materials. In addition, this method showed distinguishing site-selectivity toward the existing transition-metal-catalyzed HIE process, leading to multideuterated (hetero)aryl bromides in one step.

6.
Food Funct ; 12(3): 1039-1050, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33433542

RESUMO

Pueraria lobata is utilized as a food source in China. The aim of this study is to combine virtual screening and molecular dynamics predictive model to screen out the potential synaptic plasticity-maintaining components from the root of P. lobate and to verify it by employing the amyloid ß-injected rats' model. Eighteen compounds were identified by HPLC-MS/MS; puerarin manifested the most potential to form a stable complex with calcium/calmodulin kinase IIα (CaMK IIα), which is the key protein in synaptic plasticity by the in silico study. The further in vivo assay showed that puerarin could elevate the synaptic thickness, density, and length, relieve calcium overload, regulate the expression of CaMK IIα, and other p38MAPK-CREB signaling pathway-related biochemical criteria. The behavioral test also verified the results. Results have confirmed that the root of P. lobate can work anti-AD by maintaining the synaptic plasticity and proved the reliability of using the in silico predictive model to determine active ingredients from the natural product.


Assuntos
Doença de Alzheimer/metabolismo , Produtos Biológicos/farmacologia , Simulação de Acoplamento Molecular , Plasticidade Neuronal/efeitos dos fármacos , Raízes de Plantas/química , Pueraria/química , Peptídeos beta-Amiloides/genética , Peptídeos beta-Amiloides/metabolismo , Animais , Produtos Biológicos/química , Cálcio/metabolismo , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/genética , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Hipocampo/citologia , Hipocampo/efeitos dos fármacos , Humanos , Isoflavonas/química , Isoflavonas/farmacologia , Neurônios/efeitos dos fármacos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Proteínas/genética , Proteínas/metabolismo , Ratos , Ratos Sprague-Dawley , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
7.
Ann Vasc Surg ; 73: 344-350, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33383139

RESUMO

BACKGROUND: One of the ongoing debates about carotid endarterectomy (CEA) is the closure technique of arterial wall in the operation. Current guidelines recommend routine patch closure (PAC); this recommendation is based on the evidence reported 10-20 years ago. Therefore, the exact role of PAC and primary closure (PRC) remains uncertain. The objectives of this study were to compare the perioperative and long-term outcomes of patients who underwent CEA with different closure techniques. METHODS: From January 2013 and December 2018, one senior vascular surgeon performed CEA for 126 patients in the First Affiliated Hospital, Sun Yat-sen University. The closure technique (PAC or PRC) was determined on the characteristics (diameter and level) of carotid arteries. Patient demographics and clinical data were retrospectively collected by two research fellows by reviewing the hospital medical records and relevant radiologic studies, as were carotid duplex reports, indications, intraoperative data, closure technique, and perioperative complications. Data of long-term outcomes were gathered by reviewing outpatient clinic visits and associated supplementary examinations. RESULTS: PRC was performed in 78 operations (61.9%), and PAC was performed in 48 operations (38.1%). There were no statistical differences in demographic and clinical data between the two groups. Carotid clamp time (P < 0.001) and operating time (P < 0.001) were significantly longer when performing PAC (P < 0.001), and intraoperative blood loss was significantly more when performing PAC than that of PRC (P < 0.001). The postoperative outcome and the follow-up results showed that there was no significant difference in the short-term and middle-term overall survival rate and restenosis-free survival rate between the two groups. CONCLUSIONS: There are no differences in postoperative and middle-term outcomes between PAC and selective PRC, whereas PRC technique can save operation time and shorten the intraoperative carotid clamp time. PRC can be safely applied in patients with a greater than 5 mm internal carotid artery (ICA).

8.
Talanta ; 221: 121607, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33076137

RESUMO

Drug-induced liver injury (DILI) has been a hot issue of public health, owing to its unpredictability and serious harm to public health. Peroxynitrite (ONOO-) is an important biomarker for the assessment and diagnosis of DILI. In this article, based on a kind of rhodamine analogue with a near-infrared (NIR) emission (610 nm-800 nm) and a two-photon absorption cross section (54 GM), a two-photon excited NIR fluorescence probe (NIR-ONOO) for ONOO- was developed. With a high selectivity and a high sensitivity to ONOO-, NIR-ONOO has a linear range for detection of ONOO- from 5.0 × 10-8 to 1.0 × 10-5 M, a good detection limit (15 nM) and a large fluorescence enhancement (340-fold). In addition, NIR-ONOO has been used to monitor ONOO- in cells with satisfactory results. Because of its two-photon excied NIR emission, NIR-ONOO also showed excellent performances for imaging ONOO- including low autofluorescence, stable and persistent fluorescence, and a deep penetration (204 µm). Finally, NIR-ONOO was successfully employed to image ONOO- in inflammatory mouse, drug-induced hepatotoxicity in cells and its remediation. All the results indicated that NIR-ONOO is a powerful chemical tool to image ONOO- and assay drug-induced hepatotoxicity.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas , Preparações Farmacêuticas , Animais , Doença Hepática Induzida por Substâncias e Drogas/diagnóstico por imagem , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Corantes Fluorescentes , Camundongos , Ácido Peroxinitroso/toxicidade , Fótons
9.
Clin Chim Acta ; 511: 269-277, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33148529

RESUMO

Feasible and accurate predictors are urgently needed to evaluate the survival for patients with paraquat poisoning since the high mortality of paraquat poisoning always resulted in the loss of both life and money. Multiple predictors have been developed to predict prognosis of the patients with PQ poisoning, which however heavily depend on the time of admission to hospitals. Here we reported a feasible and accurate prognosis predictor for patients with paraquat poisoning that is independent of the time of admission to hospitals. Patients with paraquat poisoning were enrolled in this study according to the inclusion and exclusion criteria, which were grouped into survivors and non-survivors based on the 90-days follow-up investigation. The concentration of paraquat in serum and urine, and the baseline clinical parameters associated with the injuries of the liver, kidney, and lung were evaluated to predict the survival of these patients by using receiver operating characteristic curve (ROC) analysis, univariate and multivariate cox regression analyses. A total of 114 patients was included in this study with a survival rate of 54.4%. The median survival days of non-survivors were 6.0 (95%Cl: 4.0-7.8). A new predictor, namely paraquat concentration-associated multiorgan injury index (PCAMII), was established by integrating serum and urine paraquat concentration, serum creatinine, alanine aminotransferase, aspartate transaminase, total and direct bilirubin, at different weighting coefficients, with the accuracy of about 90%. The model to predict the survival probability by PCAMII was established with good fitness (R2 = 0.9325), providing the simulated survival rates comparable to the clinical data. PCAMII, which is independent of hospital admission time, is a feasible and accurate marker to predict the survival rate of patients with PQ poisoning.


Assuntos
Paraquat , Humanos , Prognóstico , Curva ROC , Estudos Retrospectivos , Taxa de Sobrevida
10.
Int J Oncol ; 57(6): 1383, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33174015

RESUMO

Following the publication of this paper, it was drawn to the authors' attention by an interested reader that some tumours featured in Fig. 6A of the above paper were strikingly similar to those featured in Fig. 8A of an article appearing in the same journal [Fan F­Y, Deng R, Yi H, Sun H­P, Zeng Y, He G­C and Su Y: The inhibitory effect of MEG3/miR­214/AIFM2 axis on the growth of T­cell lymphoblastic lymphoma. Int J Oncol 51: 316­326, 2017]. Furthermore, flow cytometric images featured in Fig. 2G of the above paper were strikingly similar to data featured in the following article [Zhang H­j, Wei Q­f, Wang S­j, Zhang H­j, Zhang X­y, Geng Q, Cui Y­h and Wang X­h: LncRNA HOTAIR alleviates rheumatoid arthritis by targeting miR­138 and inactivating NF­κB pathway. Int Immunopharmacol 50: 283­290, 2017]. The Editor asked the authors for an explanation to account for the appearance of strikingly similar data in their paper independently, and they responded to request that the paper be retracted from International Journal of Oncology. All the authors agreed that the article should be retracted. The Editor apologizes to the readership for any inconvenience caused. [the original article was published in International Journal of Oncology 50: 1821­1831, 2017; DOI: 10.3892/ijo.2017.3943].

11.
Org Biomol Chem ; 18(34): 6627-6633, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32832955

RESUMO

An efficient approach to install deuterium into mono-fluorinated (hetero)arenes by a Ag2CO3/Sphos-mediated HIE protocol with D2O as the deuterium source has been disclosed. This method showed a specific site selectivity of deuteration at the α-position of the fluorine atom, which is complementary to the existing transition metal-catalyzed HIE process.

12.
World J Gastroenterol ; 26(27): 3917-3928, 2020 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-32774066

RESUMO

BACKGROUND: Chronic hepatitis B virus (HBV) infection is a leading cause of liver morbidity and mortality worldwide. Liver fibrosis resulting from viral infection-associated inflammation and direct liver damage plays an important role in disease management and prognostication. The mechanisms underlying the contribution of the liver microenvironment to fibrosis in HBV patients are not fully understood. There is an absence of effective clinical treatments for liver fibrosis progression; thus, establishing a suitable in vitro microenvironment in order to design novel therapeutics and identify molecular biomarkers to stratify patients is urgently required. AIM: To examine a subset of pre-selected microenvironment factors of chronic HBV patients that may underlie fibrosis, with a focus on fibroblast activation. METHODS: We examined the gene expression of key microenvironment factors in liver samples from patients with more advanced fibrosis compared with those with less severe fibrosis. We also used the human stellate cell line LX-2 in the in vitro study. Using different recombinant cytokines and growth factors or their combination, we studied how these factors interacted with LX-2 cells and pinpointed the cross-talk between the aforementioned factors and screened the most important factors. RESULTS: Of the secreted factors examined, transforming growth factor (TGF)-ß1, interleukin (IL)-1ß and tumor necrosis factor (TNF)-α were increased in patients with advanced fibrosis. We found that besides TGF-ß1, IL-1ß can also induce a profibrotic cascade by stimulating the expression of connective tissue growth factor and platelet-derived growth factor (PDGF) in LX-2 cells. Furthermore, the proinflammatory response can be elicited in LX-2 cells following treatment with IL-1ß and TNF-α, suggesting that stellate cells can respond to proinflammatory stimuli. By combining IL-1ß and TGF-ß1, we observed not only fibroblast activation as shown by αlpha-smooth muscle actin and PDGF induction, but also the inflammatory response as shown by increased expression of IL-1ß. CONCLUSION: Collectively, our data from HBV patients and in vitro studies demonstrate that the hepatic microenvironment plays an important role in mediating the crosstalk between profibrotic and proinflammatory responses and modulating fibrosis in chronic HBV patients. For the establishment of a suitable in vitro microenvironment for HBV-induced liver fibrosis, not only TGF-ß1 but also IL-1ß should be considered as a necessary environmental factor.


Assuntos
Hepatite B Crônica , Cirrose Hepática , Adulto , Feminino , Células Estreladas do Fígado/patologia , Hepatite B Crônica/complicações , Hepatite B Crônica/patologia , Humanos , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Fator de Crescimento Derivado de Plaquetas , Fator de Crescimento Transformador beta1 , Fator de Necrose Tumoral alfa
13.
Nanotechnology ; 31(46): 465102, 2020 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-32857735

RESUMO

The biological effects of nanoparticles are of great importance for the in-depth understanding of safety issues in biomedical applications. Induction of autophagy is a cellular response after nanoparticle exposure. Bismuth sulfide nanoparticles (Bi2S3 NPs) are often used as a CT contrast agent because of their excellent photoelectric conversion ability. Yet there has been no previous detailed study other than a cell toxicity assessment. In this study, three types of Bi2S3 NPs with different shapes (Bi2S3 nano rods (BSNR), hollow microsphere Bi2S3 NPs (BSHS) and urchin-like hollow microsphere Bi2S3 NPs (ULBSHS)) were used to evaluatecytotoxicity, autophagy induction, cell migration and invasion in human hepatocellular carcinoma cells (HepG2). Results showed that all three Bi2S3 NPs lead to blockage in autophagic flux, causing p62 protein accumulation. The cell death caused by these Bi2S3 NPs is proved to be autophagy related, rather than related to apoptosis. Moreover, Bi2S3 NPs can reduce the migration and invasion in HepG2 cells in an autophagy-dependent manner. ULBSHS is the most cytotoxic among three Bi2S3 NPs and has the best tumor metastasis suppression. These results demonstrated that, even with relatively low toxicity of Bi2S3 NPs, autophagy blockage may still substantially influence cell fate and thus significantly impact their biomedical applications, and that surface topography is a key factor regulating their biological response.


Assuntos
Autofagia/efeitos dos fármacos , Bismuto/efeitos adversos , Movimento Celular/efeitos dos fármacos , Citotoxinas/efeitos adversos , Nanopartículas/efeitos adversos , Sulfetos/efeitos adversos , Bismuto/química , Bismuto/toxicidade , Citotoxinas/química , Citotoxinas/toxicidade , Células Hep G2 , Humanos , Nanopartículas/química , Nanopartículas/toxicidade , Sulfetos/química , Sulfetos/toxicidade
14.
Oncogene ; 39(35): 5768-5781, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32719439

RESUMO

Cumulative evidence suggests that microRNAs (miRNAs) promote gene expression in cancers. However, the pathophysiologic relevance of miRNA-mediated RNA activation in hepatocellular carcinoma (HCC) remains to be established. Our previous miRNA expression profiling in seven-paired HCC specimens revealed miR-93-5p as an HCC-related miRNA. In this study, miR-93-5p expression was assessed in HCC tissues and cell lines by quantitative real-time PCR and fluorescence in situ hybridization. The correlation of miR-93-5p expression with survival and clinicopathological features of HCC was determined by statistical analysis. The function and potential mechanism of miR-93-5p in HCC were further investigated by a series of gain- or loss-of-function experiments in vitro and in vivo. We identified that miR-93-5p, overexpressed in HCC specimens and cell lines, leads to poor outcomes in HCC cases and promotes proliferation, migration, and invasion in HCC cell lines. Mechanistically, rather than decreasing target mRNA levels as expected, miR-93-5p binds to the 3'-untranslated region (UTR) of mitogen-activated protein kinase kinase kinase 2 (MAP3K2) to directly upregulate its expression and downstream p38 and c-Jun N-terminal kinase (JNK) pathway, thereby leading to cell cycle progression in HCC. Notably, we also demonstrated that c-Jun, a downstream effector of the JNK pathway, enhances miR-93-5p transcription by targeting its promoter region. Besides, downregulation of miR-93-5p significantly retarded tumor growth, while overexpression of miR-93-5p accelerated tumor growth in the HCC xenograft mouse model. Altogether, we revealed a miR-93-5p/MAP3K2/c-Jun positive feedback loop to promote HCC progression in vivo and in vitro, representing an RNA-activating role of miR-93-5p in HCC development.


Assuntos
Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , MAP Quinase Quinase Quinase 2/metabolismo , MicroRNAs/metabolismo , Proteínas Proto-Oncogênicas c-jun/metabolismo , Regiões 3' não Traduzidas , Animais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Células Hep G2 , Xenoenxertos , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MAP Quinase Quinase Quinase 2/biossíntese , MAP Quinase Quinase Quinase 2/genética , Masculino , Camundongos , Camundongos Nus , MicroRNAs/genética , Invasividade Neoplásica , Fosforilação , Regiões Promotoras Genéticas , Proteínas Proto-Oncogênicas c-jun/genética , Transfecção , Regulação para Cima
15.
Ann Surg Oncol ; 27(5): 1546-1557, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32157528

RESUMO

BACKGROUND: The mechanistic target of rapamycin (mTOR) pathway, containing mTOR complex 1 (mTORC1) and mTORC2, is dysregulated in multiple cancers, including hepatocellular carcinoma (HCC). Mammalian lethal with sec-13 protein 8 (mLST8) is a shared constituent of both mTORC1 and mTORC2, yet little is known regarding its role in HCC development. METHODS: mLST8 expression was detected in a total of 186 pairs of HCC and adjacent non-tumor specimens. The correlation between mLST8 level and clinicopathological features or prognostic significance were analyzed. The role of mLST8 on biological functions was also preliminarily studied. RESULTS: The study revealed that the mLST8 level was dramatically higher in HCC specimens than in adjacent non-tumor specimens. mLST8 overexpression positively correlated with tumor size, differentiation, and vessel invasion. Cases with elevated mLST8 level had more unfavorable overall survival (OS) and disease-free survival (DFS) than those with downregulated mLST8 level. Multivariate analysis demonstrated that mLST8 upregulation was an independent predictive marker for OS and DFS. Calibration curves from nomogram models indicated an excellent coherence between nomogram prediction and actual situation. Decision curve analysis proved that mLST8-based nomograms presented much higher predictive accuracy when compared with conventional clinical staging systems. Mechanistically, mLST8 enhanced cell proliferation and invasion through the AKT (protein kinase B) pathway. CONCLUSIONS: Our study demonstrates that mLST8 exerts an oncogenic role in HCC and may become a promising prognostic biomarker and therapeutic target for HCC patients.


Assuntos
Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , Homólogo LST8 da Proteína Associada a mTOR/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Linhagem Celular Tumoral , Proliferação de Células/genética , Progressão da Doença , Intervalo Livre de Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Nomogramas , Prognóstico , Regulação para Cima , Adulto Jovem
16.
Histopathology ; 76(7): 997-1004, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32096885

RESUMO

AIMS: Pulmonary peripheral glandular papilloma (GP) and mixed squamous cell and glandular papilloma (MP) have very similar histological features to pulmonary ciliated muconodular papillary tumour (CMPT)/bronchiolar adenoma (BA). The underlying genetic relationships between GP/MP and CMPT/BA have rarely been characterised. We aimed to reveal the relationship between them. METHODS AND RESULTS: We performed a clinicopathological review and next-generation sequencing (NGS) study of two GPs and five MPs. Histologically, GPs/MPs showed similar cellular and architectural features to CMPTs/BAs, such as bilayered epithelium, bronchiole-associated lesions and skipping (discontinuous) growth pattern. One MP showed partial and inconspicuous endobronchiolar growth and more glandular structures, which was very similar to the appearance of CMPT/BA. BRAF V600E mutation was detected in four papillomas (57.1%, one GP and three MPs). CONCLUSIONS: Overlapping morphological features and comparable mutation profiles support that peripheral GPs/MPs and CMPTs/BAs are on the same disease spectrum. We propose expanding the concept of CMPT/BA and including GP and MP in the CMPT/BA family.


Assuntos
Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Papiloma/genética , Papiloma/patologia , Proteínas Proto-Oncogênicas B-raf/genética , Idoso , Células Epiteliais/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação
17.
Ann Vasc Surg ; 63: 108-116, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31536795

RESUMO

BACKGROUND: This study aims to present the performance data on stent-graft and multilayer bare stents (MBS) joint technique in the treatment of high-risk thoracoabdominal aortic aneurysm (TAAA). METHODS: From May 2012 to December 2015, 8 selective TAAA cases (ages 46-75 years) ineligible for surgical repair underwent the stent-graft and MBS joint procedure, and were closely followed up for a median of 32 months (range 14-58). Using computed tomography images, the aneurysm size, luminal blood flow diameter, and the covered visceral branches were analyzed. RESULTS: Technical success was achieved in all patients (100%, 8/8). Twenty-four visceral branches were covered by MBS in total. There was no complication or death during hospital stay. During follow-up period, no death or complication occurred. Aneurysm shrinkage (maximum diameter decrease ≥5 mm) was observed in 7 patients. No aneurysm expansion was observed. Total aneurysm sac thrombosis was observed in all patients. The majority of covered side branches (23/24) were successfully preserved. No visceral ischemia or bleeding complications was observed during follow-up. CONCLUSIONS: Total endovascular repair of TAAA using stent-graft and MBS joint technique may be a safe and effective alternative in high surgical risk patients. More approving clinical evidences about the safety and efficacy of this procedure are anticipated.


Assuntos
Aneurisma da Aorta Torácica/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Stents , Idoso , Aneurisma da Aorta Torácica/diagnóstico por imagem , Implante de Prótese Vascular/efeitos adversos , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
18.
J Cell Biochem ; 121(4): 2938-2949, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31692072

RESUMO

BACKGROUND: Calcium-binding tyrosine phosphorylation-regulated protein (CABYR) is a group of isoforms produced by alternative splicing and is overexpressed in human malignancies including hepatocellular carcinoma (HCC). However, the prognostic value and biological functions of its major protein isoforms, named CABYR-a/b (combined CABYR-a and CABYR-b), in HCC remain to be established. METHODS: CABYR-a/b expression was detected in HCC tissues and cell lines by quantitative real-time polymerase chain reaction and Western blot analysis. The correlation of CABYR-a/b expression with clinical characteristics and its prognosis impact were determined by statistical analysis. Finally, the biological functions and molecular mechanism of CABYR-a/b were also investigated using molecular biology approaches. RESULTS: The present research found that CABYR-a/b was markedly elevated in HCC specimens and cell lines. Upregulated CABYR-a/b level had positive association with tumor size and differentiation in patients. Moreover, cases with elevated CABYR-a/b level had poorer overall survival (OS) and disease-free survival (DFS) than those with reduced CABYR-a/b level. Multivariate analysis and prognostic nomograms demonstrated that CABYR-a/b overexpression was an independent predictive indicator for OS and DFS. The calibration curve for the odds of OS and DFS demonstrated that the prediction by nomograms was in excellent accordance with actual situation. CABYR-a/b downregulation suppressed cell proliferation and induced G1-phase arrest via decreasing cyclin D1 and cyclin dependent kinase 4, while promoted apoptosis by reducing B-cell lymphoma 2 (Bcl-2) and increasing Bcl-2-associated death promoter. CONCLUSION: Our research indicates that CABYR-a/b exerts an oncogenic effect on HCC development and may become a new prognostic indicator for patients with HCC.

19.
Anal Chim Acta ; 1092: 117-125, 2019 Dec 27.
Artigo em Inglês | MEDLINE | ID: mdl-31708024

RESUMO

Heat stroke is a symptom of hyperthermia with a temperature of more than 40 °C, which usually leads to all kinds of physical discomfort and even death. It is necessary to study the mechanism of action of heat stroke on cells or organelles (such as cytotoxicity of heat) and the processes of cells or organelles during heat stroke. Recent studies have shown that there is a certain correlation between heat stroke and lysosome acidity. In order to clarify their relationship, Lyso-NIR-pH, a photostable Si-rhodamine-based near-infrared fluorescent probe, was developed for sensing pH changes in lysosomes during heat stroke in this paper. For Lyso-NIR-pH, a morpholine group is employed as the lysosome-targeting unit and a H+-triggered openable deoxylactam is employed as the response unit to pH. Lyso-NIR-pH can detect pH with a high selectivity and a sensitivity, and its pKa is 4.63. Lyso-NIR-pH also has outstanding imaging performances, such as excellent lysosome-targeting ability, low autofluorescence and photostable fluorescence signal, which are in favor of long-term imaging of pH with accurate fluorescence signals. Moreover, we successfully applied Lyso-NIR-pH to monitor lysosomal pH increases induced by chloroquine and apoptosis in live cells. Finally, we successfully applied Lyso-NIR-pH for monitoring changes of lysosomal pH during heat stroke. These results confirmed that Lyso-NIR-pH is a powerful tool to monitor pH change in lysosomes and study its possible effects.


Assuntos
Corantes Fluorescentes/química , Golpe de Calor/fisiopatologia , Lisossomos/metabolismo , Compostos de Organossilício/química , Rodaminas/química , Apoptose/fisiologia , Linhagem Celular Tumoral , Cloroquina/farmacologia , Corantes Fluorescentes/síntese química , Humanos , Concentração de Íons de Hidrogênio , Lisossomos/efeitos dos fármacos , Microscopia Confocal/métodos , Microscopia de Fluorescência/métodos , Compostos de Organossilício/síntese química , Rodaminas/síntese química
20.
Chem Commun (Camb) ; 55(83): 12579, 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31584587

RESUMO

Correction for 'Cascade alkylation and deuteration with aryl iodides via Pd/norbornene catalysis: an efficient method for the synthesis of congested deuterium-labeled arenes' by Lei Guo et al., Chem. Commun., 2019, 55, 8567-8570.

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