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1.
Clin Breast Cancer ; 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38423948

RESUMO

BACKGROUND: Hypoxia is a hallmark of breast cancer (BC). Photoacoustic (PA) imaging, based on the use of laser-generated ultrasound (US), can detect oxygen saturation (So2) in the tissues of breast lesion patients. PURPOSE: To measure the oxygenation status of tissue in and on both sides of the lesion in breast lesion participants using a multimodal Photoacoustic/ultrasound (PA/US) imaging system and to determine the correlation between So2 measured by PA imaging and benign or malignant disease. MATERIALS AND METHODS: Multimodal PA/US imaging and gray-scale US (GSUS) of breast lesion was performed in consecutive breast lesion participants imaged in the US Outpatient Clinic between 2022 and 2023. Dual-wavelength PA imaging was used to measure the So2 value inside the lesion and on both sides of the tissue, and to distinguish benign from malignant lesions based on the So2 value. The ability of So2 to distinguish benign from malignant breast lesions was evaluated by the receiver operating characteristic curve (ROC) and the De-Long test. RESULTS: A total of 120 breast lesion participants (median age, 42.5 years) were included in the study. The malignant lesions exhibited lower So2 levels compared to benign lesions (malignant: 71.30%; benign: 83.81%; P < .01). Moreover, PA/US imaging demonstrates superior diagnostic results compared to GSUS, with an area under the curve (AUC) of 0.89 versus 0.70, sensitivity of 89.58% versus 85.42%, and specificity of 86.11% versus 55.56% at the So2 cut-off value of 78.85 (P < .001). The false positive rate in GSUS reduced by 30.75%, and the false negative rate diminished by 4.16% with PA /US diagnosis. Finally, the So2 on both sides tissues of malignant lesions are lower than that of benign lesions (P < .01). CONCLUSION: PA imaging allows for the assessment of So2 within the lesions of breast lesion patients, thereby facilitating a superior distinction between benign and malignant lesions.

2.
Comput Methods Programs Biomed ; 245: 108039, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38266556

RESUMO

BACKGROUND: The risk of ductal carcinoma in situ (DCIS) identified by biopsy often increases during surgery. Therefore, confirming the DCIS grade preoperatively is necessary for clinical decision-making. PURPOSE: To train a three-classification deep learning (DL) model based on ultrasound (US), combining clinical data, mammography (MG), US, and core needle biopsy (CNB) pathology to predict low-grade DCIS, intermediate-to-high-grade DCIS, and upstaged DCIS. MATERIALS AND METHODS: Data of 733 patients with 754 DCIS cases confirmed by biopsy were retrospectively collected from May 2013 to June 2022 (N1), and other data (N2) were confirmed by biopsy as low-grade DCIS. The lesions were randomly divided into training (n=471), validation (n=142), and test (n = 141) sets to establish the DCIS-Net. Information on the DCIS-Net, clinical (age and sign), US (size, calcifications, type, breast imaging reporting and data system [BI-RADS]), MG (microcalcifications, BI-RADS), and CNB pathology (nuclear grade, architectural features, and immunohistochemistry) were collected. Logistic regression and random forest analyses were conducted to develop Multimodal DCIS-Net to calculate the specificity, sensitivity, accuracy, receiver operating characteristic curve, and area under the curve (AUC). RESULTS: In the test set of N1, the accuracy and AUC of the multimodal DCIS-Net were 0.752-0.766 and 0.859-0.907 in the three-classification task, respectively. The accuracy and AUC for discriminating DCIS from upstaged DCIS were 0.751-0.780 and 0.829-0.861, respectively. In the test set of N2, the accuracy and AUC of discriminating low-grade DCIS from upstaged low-grade DCIS were 0.769-0.987 and 0.818-0.939, respectively. DL was ranked from one to five in the importance of features in the multimodal-DCIS-Net. CONCLUSION: By developing the DCIS-Net and integrating it with multimodal information, diagnosing low-grade DCIS, intermediate-to high-grade DCIS, and upstaged DCIS is possible. It can also be used to distinguish DCIS from upstaged DCIS and low-grade DCIS from upstaged low-grade DCIS, which could pave the way for the DCIS clinical workflow.


Assuntos
Neoplasias da Mama , Calcinose , Carcinoma Ductal de Mama , Carcinoma Intraductal não Infiltrante , Patologia Cirúrgica , Humanos , Feminino , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/cirurgia , Estudos Retrospectivos , Mamografia , Neoplasias da Mama/diagnóstico por imagem
3.
Autophagy ; : 1-3, 2023 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-38013411

RESUMO

The CGAS (cyclic GMP-AMP synthase)-STING1 (stimulator of interferon response cGAMP interactor 1) pathway is an important innate immune pathway that induces proinflammatory cytokine production following stimulation with dsDNA > 45 bp. We recently identified a class of ~ 20-40 bp small cytosolic dsDNA (scDNA) that blocks CGAS-STING1 activation. In this punctum, we discuss the mechanism underlying the inhibition of CGAS-STING1 activation via scDNA. scDNA binds to CGAS but cannot activate its enzymatic activity. It competes with dsDNA > 45 bp for binding with CGAS to inhibit CGAS-STING1 activation. Moreover, scDNA activates macroautophagy/autophagy and induces the autophagic degradation of STING1 and long dsDNA. Autophagy then increases scDNA levels, driving a feedback loop that accelerates the degradation of STING1 and long cytosolic dsDNA. These findings reveal that mutual communication between scDNA and autophagy inhibits CGAS-STING1 activation following stimulation with dsDNA > 45 bp.

4.
BMC Med Inform Decis Mak ; 23(1): 174, 2023 09 04.
Artigo em Inglês | MEDLINE | ID: mdl-37667320

RESUMO

BACKGROUND: This retrospective study aims to validate the effectiveness of artificial intelligence (AI) to detect and classify non-mass breast lesions (NMLs) on ultrasound (US) images. METHODS: A total of 228 patients with NMLs and 596 volunteers without breast lesions on US images were enrolled in the study from January 2020 to December 2022. The pathological results served as the gold standard for NMLs. Two AI models were developed to accurately detect and classify NMLs on US images, including DenseNet121_448 and MobileNet_448. To evaluate and compare the diagnostic performance of AI models, the area under the curve (AUC), accuracy, specificity and sensitivity was employed. RESULTS: A total of 228 NMLs patients confirmed by postoperative pathology with 870 US images and 596 volunteers with 1003 US images were enrolled. In the detection experiment, the MobileNet_448 achieved the good performance in the testing set, with the AUC, accuracy, sensitivity, and specificity were 0.999 (95%CI: 0.997-1.000),96.5%,96.9% and 96.1%, respectively. It was no statistically significant compared to DenseNet121_448. In the classification experiment, the MobileNet_448 model achieved the highest diagnostic performance in the testing set, with the AUC, accuracy, sensitivity, and specificity were 0.837 (95%CI: 0.990-1.000), 70.5%, 80.3% and 74.6%, respectively. CONCLUSIONS: This study suggests that the AI models, particularly MobileNet_448, can effectively detect and classify NMLs in US images. This technique has the potential to improve early diagnostic accuracy for NMLs.


Assuntos
Inteligência Artificial , Mama , Humanos , Estudos Retrospectivos , Ultrassonografia , Área Sob a Curva
5.
Cell Rep ; 42(8): 112852, 2023 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-37481718

RESUMO

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway is a major mediator of inflammation following stimulation with >45 bp double-stranded DNA (dsDNA). Herein, we identify a class of ∼20-40 bp small cytosolic dsDNA (scDNA) molecules that compete with long dsDNA (200-1,500 bp herring testis [HT]-DNA) for binding to cGAS, thus repressing HT-DNA-induced cGAS activation. The scDNA promotes cGAS and Beclin-1 interaction, releasing Rubicon, a negative regulator of phosphatidylinositol 3-kinase class III (PI3KC3), from the Beclin-1-PI3KC3 complex. This leads to PI3KC3 activation and induces autophagy, causing degradation of STING and long cytosolic dsDNA. Moreover, DNA damage decreases, and autophagy inducers increase scDNA levels. scDNA transfection and treatment with autophagy inducers attenuate DNA damage-induced cGAS activation. Thus, scDNA molecules serve as effective brakes for cGAS activation, preventing excessive inflammatory cytokine production following DNA damage. Our findings may have therapeutic implications for cytosolic DNA-associated inflammatory diseases.


Assuntos
DNA , Proteínas de Membrana , Masculino , Humanos , Proteína Beclina-1 , Proteínas de Membrana/metabolismo , DNA/metabolismo , Nucleotidiltransferases/metabolismo , Fosfatidilinositol 3-Quinase , Autofagia
6.
J Colloid Interface Sci ; 630(Pt B): 776-785, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-36356445

RESUMO

Exposure to ammonia (NH3) is known harmful to health, environment and industrial facilities, hence it is important for the trace detection of NH3. Herein, for the first time, ultrasensitive room temperature NH3 sensors are realized by assembling carbon quantum dots (CQDs) on free-standing ultrathin coordination polymers (CPs) nanosheets (Co[Ni(CN)4]) with an average thickness of ∼2.5 nm, which demonstrate excellent sensitivity (Ra/Rg = 87.7 to 30 ppm), fast gas response speed (∼10 s to 30 ppm), remarkable repeatability, high selectivity, good long-term stability and low limit of theoretical detection (∼8 ppb) toward NH3 gas. The NH3 gas sensor enhancement through incorporation of CQDs provides a simple and environment-friendly strategy for further improving sensor property of CPs nanosheets. This work provides an effective way to construct new electrode materials for high-performance gas sensor devices via the rational design.


Assuntos
Pontos Quânticos , Carbono , Amônia , Polímeros
7.
Front Immunol ; 14: 1313536, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38187400

RESUMO

Introduction: Bone metastasis (BoM) occurs when cancer cells spread from their primary sites to a bone. Currently, the mechanism underlying this metastasis process remains unclear. Methods: In this project, through an integrated analysis of bulk-sequencing and single-cell RNA transcriptomic data, we explored the BoM-related features in tumor microenvironments of different tumors. Results: We first identified 34 up-regulated genes during the BoM process in breast cancer, and further explored their expression status among different components in the tumor microenvironment (TME) of BoM samples. Enriched EMP1+ fibroblasts were found in BoM samples, and a COL3A1-ADGRG1 communication between these fibroblasts and cancer cells was identified which might facilitate the BoM process. Moreover, a significant correlation between EMP1 and COL3A1 was identified in these fibroblasts, confirming the potential connection of these genes during the BoM process. Furthermore, the existence of these EMP1+/COL3A1+ fibroblasts was also verified in prostate cancer and renal cancer BoM samples, suggesting the importance of these fibroblasts from a pan-cancer perspective. Discussion: This study is the first attempt to investigate the relationship between fibroblasts and BoM process across multi-tumor TMEs. Our findings contribute another perspective in the exploration of BoM mechanism while providing some potential targets for future treatments of tumor metastasis.


Assuntos
Neoplasias Ósseas , Carcinoma de Células Renais , Neoplasias Renais , Melanoma , Segunda Neoplasia Primária , Neoplasias Cutâneas , Masculino , Humanos , Próstata , Neoplasias Renais/genética , Neoplasias Ósseas/genética , Fibroblastos , Microambiente Tumoral/genética , Colágeno Tipo III
8.
Nanoscale ; 14(43): 16220-16232, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36281819

RESUMO

Semiconductors exhibit great potential as a surface enhanced Raman scattering (SERS) substrate due to their low cost, good stability and biocompatibility. However, the extensive application of semiconductors has been restricted by their intrinsically low SERS sensitivity. It is urgently required to design uniform metal oxide substrates with enhanced charge transfer and SERS activity. Herein, three facet-defined ({101̄0}, {0001} and {101̄1}) ZnO films were synthesized via an electrodeposition procedure with the assistance of KCl or ethylenediamine. According to the results, the ZnO films with {0001} and {101̄1} exposed facets exhibit appreciable SERS enhancement factors (EFs) of 1.6 × 104 and 2.8 × 104 for 4-nitrobenzenethiol (4-NBT), as well as a relatively low limit of detection (LOD) down to 1 × 10-6 M and 5 × 10-7 M, respectively. Simultaneously, the electrodeposited ZnO films deliver good repeatability and SERS stability, with relative standard deviation (RSD) less than 6% and 85.2% of their original activity retained after 40 days. Theoretical calculations verified that the {0001} and {101̄1} facets can transfer more electrons from ZnO to the molecules on account of their low facet-related electronic work functions, thus generating the noticeable improvement of SERS activity. The current study provides theoretical and technical support for the crystal facet engineering and property improvement of semiconductors.

9.
Chem Commun (Camb) ; 58(82): 11543-11546, 2022 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-36155602

RESUMO

Sensors with high-sensitivity for resistive methanol gas detection are highly desirable. Herein, we report newly designed ultrathin anionic metal-organic framework (MOF) nanosheets (NSs), with an average thickness of 10 nm and an electrical conductivity of 3.77 × 10-4 S cm-1. The ultrathin MOF NSs can be used as the active material in an electronic methanol gas sensor, which exhibits high sensitivity toward methanol gas at room temperature, i.e., high Rair/Rgas (363.2 at 100 ppm), fast gas response/recovery speed (6 s/2 s at 20 ppm), long-term stability, and superior cross-selectivity against other interfering gases.

10.
MedComm (2020) ; 3(3): e133, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35811688

RESUMO

Invasive cancer growth and metastasis account for the poor prognosis of high-grade breast cancer. Recently, we reported that kinectin 1 (KTN1), a member of the kinesin-binding protein family, promotes cell invasion of triple-negative breast cancer and high-grade breast cancer cells by augmenting the NF-κB signaling pathway. However, the upstream mechanism regulating KTN1 is unknown. Therefore, this functional study was performed to decipher the regulatory cohort of KTN1 in high-grade breast cancer. Bioinformatic analysis indicated that transcription factor Yin Yang 1 (YY1) was a potential transactivator of KTN1. High YY1 expression correlated positively with pathological progression and poor prognosis of high-grade breast cancer. Additionally, YY1 promoted cell invasive growth both in vitro and in vivo, in a KTN1-dependent manner. Mechanistically, YY1 could transactivate the KTN1 gene promoter. Alternatively, YY1 could directly interact with a co-factor, DEAD-box helicase 3 X-linked (DDX3X), which significantly co-activated YY1-mediated transcriptional expression of KTN1. Moreover, DDX3X augmented YY1-KTN1 signaling-promoted invasive cell growth of breast cancer. Importantly, overexpression of YY1 enhanced tumor aggressive growth in a mouse breast cancer model. Our findings established a novel DDX3X-assisted YY1-KTN1 regulatory axis in breast cancer progression, which could lead to the development novel therapeutic targets for breast cancer.

11.
Bioact Mater ; 6(3): 627-637, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33005827

RESUMO

Brain tissues that are severely damaged by traumatic brain injury (TBI) is hardly regenerated, which leads to a cavity or a repair with glial scarring. Stem-cell therapy is one viable option to treat TBI-caused brain tissue damage, whose use is, whereas, limited by the low survival rate and differentiation efficiency of stem cells. To approach this problem, we developed an injectable hydrogel using imidazole groups-modified gelatin methacrylate (GelMA-imid). In addition, polydopamine (PDA) nanoparticles were used as carrier for stromal-cell derived factor-1 (SDF-1α). GelMA-imid hydrogel loaded with PDA@SDF-1α nanoparticles and human amniotic mesenchymal stromal cells (hAMSCs) were injected into the damaged area in an in-vivo cryogenic injury model in rats. The hydrogel had low module and its average pore size was 204.61 ± 41.41 nm, which were suitable for the migration, proliferation and differentiation of stem cells. In-vitro cell scratch and differentiation assays showed that the imidazole groups and SDF-1α could promote the migration of hAMSCs to injury site and their differentiation into nerve cells. The highest amount of nissl body was detected in the group of GelMA-imid/SDF-1α/hAMSCs hydrogel in the in-vivo model. Additionally, histological analysis showed that GelMA-imid/SDF-1α/hAMSCs hydrogel could facilitate the regeneration of regenerate endogenous nerve cells. In summary, the GelMA-imid/SDF-1α/hAMSCs hydrogel promoted homing and differentiation of hAMSCs into nerve cells, and showed great application potential for the physiological recovery of TBI.

12.
Adv Sci (Weinh) ; 7(21): 2001364, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33173727

RESUMO

Acetylation is a critical mechanism to modulate tumor-suppressive activity of p53, but the causative roles of long non-coding RNAs (lncRNAs) in p53 acetylation and their biological significance remain unexplored. Here, lncRNA LOC100294145 is discovered to be transactivated by p53 and is thus designated as lnc-Ip53 for lncRNA induced by p53. Furthermore, lnc-Ip53 impedes p53 acetylation by interacting with histone deacetylase 1 (HDAC1) and E1A binding protein p300 (p300) to prevent HDAC1 degradation and attenuate p300 activity, resulting in abrogation of p53 activity and subsequent cell proliferation and apoptosis resistance. Mouse xenograft models reveal that lnc-Ip53 promotes tumor growth and chemoresistance in vivo, which is attenuated by an HDAC inhibitor. Silencing lnc-Ip53 inhibits the growth of xenografts with wild-type p53, but not those expressing acetylation-resistant p53. Consistently, lnc-Ip53 is upregulated in multiple cancer types, including hepatocellular carcinoma (HCC). High levels of lnc-Ip53 is associated with low levels of acetylated p53 in human HCC and mouse xenografts, and is also correlated with poor survival of HCC patients. These findings identify a novel p53/lnc-Ip53 negative feedback loop in cells and indicate that abnormal upregulation of lnc-Ip53 represents an important mechanism to inhibit p53 acetylation/activity and thereby promote tumor growth and chemoresistance, which may be exploited for anticancer therapy.

13.
Arthritis Res Ther ; 22(1): 239, 2020 10 14.
Artigo em Inglês | MEDLINE | ID: mdl-33054864

RESUMO

BACKGROUND: Necroptosis is a form of regulated necrosis that is involved in various autoimmune diseases. Mixed lineage kinase domain-like pseudokinase (MLKL) has been identified as a key executor of necroptosis; however, the significance of MLKL in peripheral blood mononuclear cells (PBMCs) of systemic lupus erythematosus (SLE) has not been investigated. In this study, we aimed to determine the mRNA level of MLKL in PBMCs and examine its relationship with clinical features and serological parameters in SLE. METHODS: Real-time transcription-polymerase chain reaction (RT-PCR) analysis was used to determine the expression of MLKL mRNA in PBMCs from 59 patients with SLE, 25 patients with rheumatoid arthritis (RA), and 30 age- and sex-matched healthy controls (HC). Spearman's correlation test was performed to assess the correlation of MLKL mRNA with clinical variables. The receiver operating characteristic (ROC) curve was created to evaluate the diagnostic value. RESULTS: Our results showed MLKL mRNA in PBMCs was upregulated in SLE patients compared to that in RA and HC individuals. SLE patients positive for antinuclear antibodies had significantly higher MLKL mRNA than antibody-negative patients. In SLE patients, MLKL mRNA was found to be upregulated in patients with lupus nephritis (LN) as compared with patients without LN, and also higher in active patients than in stable patients. MLKL mRNA level was significantly and positively correlated with c-reaction protein (CRP) (r = 0.3577, p = 0.0237), erythrocyte sedimentation rate (ESR) (r = 0.4091, p = 0.0043), serum immunoglobulin G (IgG) concentration (r = 0.3546, p = 0.0289), and the numbers of positive antinuclear antibodies (ANAs) (r = 0.3945, p = 0.0432). ROC analysis showed that MLKL mRNA in PBMCs had an area under the curve of 0.9277 (95% CI 0.8779-0.9775, p < 0.001) to discriminate SLE from controls. CONCLUSIONS: These results suggest that increased MLKL mRNA level in the PBMCs of SLE patients is correlated with renal involvement and disease activity, identifying a subgroup of patients with SLE or LN who may benefit from early diagnosis and therapies targeting MLKL.


Assuntos
Lúpus Eritematoso Sistêmico , Nefrite Lúpica , Anticorpos Antinucleares , Humanos , Leucócitos Mononucleares , Lúpus Eritematoso Sistêmico/genética , Nefrite Lúpica/genética , Proteínas Quinases , RNA Mensageiro/genética
14.
Water Sci Technol ; 81(1): 91-101, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32293592

RESUMO

The sheet-like adsorbent of the eggshell wastes was prepared by the thermal hydrolysis method. The structure of the adsorbent was characterized by scanning electron microscope, Brunauer-Emmett-Teller, X-ray diffraction, transmission electron microscope, and X-ray photoelectron spectrometer. The adsorption capacity was investigated in a Pb2+ solution. The effects of initial pH, salt concentration, contact time, and adsorbate concentration on the adsorption of lead ions were investigated in detail. The morphology of the adsorbent was sheet-like microspheres. Zinc selenide/zinc oxide could be uniformly loaded onto the eggshell waste surface, which could effectively enhance the specific surface area of the eggshell wastes. The adsorption kinetics and isotherm followed the pseudo-second-order and Langmuir-Freundlich isotherm model, respectively. The synthesized adsorbent showed a maximum lead adsorption capacity of 1,428.78 mg/g at room temperature. Ion-exchange was the main adsorption mechanism.


Assuntos
Poluentes Químicos da Água , Óxido de Zinco , Adsorção , Animais , Concentração de Íons de Hidrogênio , Íons , Cinética , Chumbo , Soluções
15.
Support Care Cancer ; 27(7): 2361-2370, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30919153

RESUMO

PURPOSE: Oral mucositis is a common side effect of radiochemotherapy and may adversely affect the patients' quality of life (QoL). Honey application may reduce the mucositis grade in patients. Here, we conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the prophylactic and therapeutic effects of honey on radiochemotherapy-induced oral mucositis. METHODS: Publications on RCTs were extracted from the PubMed, Embase, CINAHL, and Cochrane Library databases. The primary outcomes were mucositis grades and pain scores. Secondary outcomes were the recovery time and QoL. The study was registered with PROSPERO (number CRD42018108486). RESULTS: Nineteen RCTs, involving 1276 patients, were reviewed. Honey considerably mitigated oral mucositis in both prophylactic and therapeutic phases. In the prophylactic phase, intolerable mucositis development was significantly prevented in the honey-treated group (RR = 0.18, 95% confidence interval [CI] = 0.09 to 0.41). Patients treated with honey showed significant decrease in pain scores in the first month of treatment (weighted mean difference [WMD] = - 3.25, 95% CI = - 4.41 to - 2.09) and at the end of the treatment (WMD = - 2.32, 95% CI = - 4.47 to - 0.18). CONCLUSION: Honey, which is relatively cheap and easily available, prevented mucositis and effectively mitigate mucositis in patients after radiochemotherapy. Moreover, it significantly reduced the mucositis grade and engendered a fast and painless healing process. Therefore, honey use during and after radiochemotherapy is recommended for mucositis prevention and treatment.


Assuntos
Quimiorradioterapia/efeitos adversos , Mel/análise , Mucosite/tratamento farmacológico , Estomatite/induzido quimicamente , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
16.
Hepatology ; 68(4): 1459-1475, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-29637568

RESUMO

Increased vascular permeability facilitates metastasis. Emerging evidence indicates that secreted microRNAs (miRNAs) may mediate the crosstalk between cancer and stromal cells. To date, whether and how secreted miRNAs affect vascular permeability remains unclear. Based on deep sequencing and quantitative PCR, we found that higher level of serum miR-103 was associated with higher metastasis potential of hepatocellular carcinoma (HCC). The in vitro endothelial permeability and transendothelial invasion assays revealed that the conditioned media or exosomes derived from high miR-103-expressing hepatoma cells increased the permeability of endothelial monolayers, but this effect was attenuated if exosome secretion of hepatoma cells was blocked by silencing ALIX and HRS or if miR-103 within hepatoma or endothelial cells was antagonized. Most importantly, pretreating endothelial monolayers with exosomes that were from stable miR-103-expressing hepatoma cells facilitated the transendothelial invasion of tumor cells, and this role of exosomes was abrogated by inhibiting miR-103 in endothelial cells. Further in vivo analyses disclosed that mice with xenografts of stable miR-103-expressing hepatoma cells exhibited higher vascular permeability in tumor, higher level of exosomal miR-103 and greater number of tumor cells in blood circulation, and increased rates of hepatic and pulmonary metastases, compared to control mice. Mechanism investigations revealed that hepatoma cell-secreted miR-103 could be delivered into endothelial cells via exosomes, and then attenuated the endothelial junction integrity by directly inhibiting the expression of VE-Cadherin (VE-Cad), p120-catenin (p120) and zonula occludens 1. Moreover, miR-103 could also promote tumor cell migration by repressing p120 expression in hepatoma cells. CONCLUSION: Hepatoma cell-secreted exosomal miR-103 increases vascular permeability and promotes tumor metastasis by targeting multiple endothelial junction proteins, which highlights secreted miR-103 as a potential therapeutic target and a predictive marker for HCC metastasis. (Hepatology 2018).


Assuntos
Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Metástase Neoplásica/genética , Transporte Proteico/genética , Animais , Biópsia por Agulha , Permeabilidade Capilar/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Exossomos/metabolismo , Hepatócitos/metabolismo , Hepatócitos/patologia , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/patologia , Camundongos , Valores de Referência , Sensibilidade e Especificidade , Transdução de Sinais , Regulação para Cima
17.
J Food Sci Technol ; 51(12): 3970-6, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25477668

RESUMO

The changes in phytate, phytase activity and in vitro availability of iron and zinc during soaking and sprouting of green and white faba bean (Vicia faba L.) were investigated. Faba bean were soaked for 24 h and germinated for 72 h after soaking for 24 h to reduce phytate content and increase iron and zinc in vitro availability. The results revealed that iron and zinc content was significantly reduced from 28.2 to 39.8 % and 12.5 to 27.6 % for soaking treatment and 38.2 to 38.9 % and 24.5 to 29.2 % for sprouting treatment, respectively. Phytate content was significantly reduced from 26.9 to 32.5 % for soaking treatment and 28.0 to 34.9 % for sprouting treatment, respectively. The results proved that the main distinct point is the change of phytase activity as well as specific activity during different treatment which showed no significant differences between the green and white faba bean. The in vitro availability of iron and zinc were significantly improved as a result of soaking and sprouting treatments.

18.
Huan Jing Ke Xue ; 35(2): 520-5, 2014 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-24812942

RESUMO

The performance of a bio-trickling filter (BTF) for treatment of phenol, a model pollutant, was presented. Influences of factors on phenol removal efficiency were studied. The BTF exhibited a high removal efficiency for phenol. The experimental results showed that the phenol efficiency reached 99.5% and kept 98% in the long-term run. The optimal residence time, pH value and spray density were 20.6 s, 7.0 and 1.67 m(3) x (m(2) x h)(-1), respectively. The microbial community structures in the bio-trickling filter for phenol removal were assessed by PCR-DGGE. Based on the 16S rDNA sequence data,results showed that the predominant bacteria for degradation of phenol were Polaromonas sp., Acinetobacter sp., Acidovorax sp., Veillonella parvula and Corynebacterium sp., GC-MS was used to detect component of BTF's outlet gases and pyruvic acid (CH3COCOOH) was found as one kind of intermediates of phenol degradation. Then one possible biodegradation pathway of phenol was inferred.


Assuntos
Bactérias/metabolismo , Filtração/métodos , Fenóis/química , Bactérias/classificação , Biodegradação Ambiental , Gases/química , RNA Ribossômico 16S/genética
19.
Cent Eur J Immunol ; 39(3): 271-8, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-26155135

RESUMO

How to evaluate status of the immune system is extremely critical for clinical immunosuppressive treatment. In this study, we tested the secretion of cytokines in undiluted whole blood samples stimulated with Phorbol 12-myristate 13-acetate (PMA) and ionomycin (IONO), and compared the effects of dexamethasone (DEX), cyclosporine A (CsA) or mycophenolic acid (MPA), either alone or in combination, on cytokine profiles. The results showed that both DEX and CsA dose-dependently inhibited the production of eleven cytokines: interleukin (IL)-2, IL-4, IL-5, IL-6, IL-13, IL-17, interferon γ (IFN-γ), tumor necrosis factor α (TNF-α), granulocyte-macrophage colony-stimulating factor (GM-CSF) and granulocyte colony-stimulating factor (G-CSF). Unexpectedly, MPA showed no obvious influences except for the mild inhibition on GM-CSF production. In combination treatment, cytokine profiles reflect not only the synergistic effects among drugs, but also the specific effect of the individual drug. Thus, the effects of different immunosuppressants could be reflected through their specific cytokine signatures, which can be applied to maximize immunosuppressive effects, while to minimize risk of infections and help physicians to reasonably apply immunosuppressants.

20.
Huan Jing Ke Xue ; 34(10): 3772-6, 2013 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-24364291

RESUMO

It can produce a large number of free radicals in O3/H2O2, system, ozone and free radical coupling oxidation can improve the styrene removal efficiency. Styrene oxidation by O3/H2O2 was investigated. Ozone dosage, residence time, H2o2 volume fraction, spray density and molar ratio of O3/C8H8 on styrene removal were evaluated. The experimental results showed that styrene removal efficiency achieved 85.7%. The optimal residence time, H2O2, volume fraction, spray density and O3/C8H8 molar ratio were 20. 6 s, 10% , 1.72 m3.(m2.h)-1 and 0.46, respectively. The gas-phase degradation intermediate products were benzaldehyde(C6H5CHO) and benzoic acid (C6H5 COOH) , which were identified by means of gas chromatography-mass spectrometry(GC-MS). The degradation mechanism of styrene is presented.


Assuntos
Peróxido de Hidrogênio/química , Ozônio/química , Estireno/química , Cromatografia Gasosa-Espectrometria de Massas , Oxirredução
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