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1.
Int J Mol Sci ; 24(7)2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37047400

RESUMO

Three waves of hematopoiesis occur in the mouse embryo. The primitive hematopoiesis appears as blood islands in the extra embryonic yolk sac at E7.5. The extra embryonic pro-definitive hematopoiesis launches in late E8 and the embryonic definitive one turns on at E10.5 indicated by the emergence of hemogenic endothelial cells on the inner wall of the extra embryonic arteries and the embryonic aorta. To study the roles of SCL protein isoforms in murine hematopoiesis, the SCL-large (SCL-L) isoform was selectively destroyed with the remaining SCL-small (SCL-S) isoform intact. It was demonstrated that SCL-S was specifically expressed in the hemogenic endothelial cells (HECs) and SCL-L was only detected in the dispersed cells after budding from HECs. The SCLΔ/Δ homozygous mutant embryos only survived to E10.5 with normal extra embryonic vessels and red blood cells. In wild-type mouse embryos, a layer of neatly aligned CD34+ and CD43+ cells appeared on the endothelial wall of the aorta of the E10.5 fetus. However, the cells at the same site expressed CD31 rather than CD34 and/or CD43 in the E10.5 SCLΔ/Δ embryo, indicating that only the endothelial lineage was developed. These results reveal that the SCL-S is sufficient to sustain the primitive hematopoiesis and SCL-L is necessary to launch the definitive hematopoiesis.


Assuntos
Células Endoteliais , Hematopoese , Camundongos , Animais , Hematopoese/genética , Desenvolvimento Embrionário/genética , Embrião de Mamíferos/metabolismo , Endotélio
2.
Int J Mol Sci ; 22(18)2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34576035

RESUMO

Theoretically, a DNA sequence-specific recognition protein that can distinguish a DNA sequence equal to or more than 16 bp could be unique to mammalian genomes. Long-sequence-specific nucleases, such as naturally occurring Homing Endonucleases and artificially engineered ZFN, TALEN, and Cas9-sgRNA, have been developed and widely applied in genome editing. In contrast to other counterparts, which recognize DNA target sites by the protein moieties themselves, Cas9 uses a single-guide RNA (sgRNA) as a template for DNA target recognition. Due to the simplicity in designing and synthesizing a sgRNA for a target site, Cas9-sgRNA has become the most current tool for genome editing. Moreover, the RNA-guided DNA recognition activity of Cas9-sgRNA is independent of both of the nuclease activities of it on the complementary strand by the HNH domain and the non-complementary strand by the RuvC domain, and HNH nuclease activity null mutant (H840A) and RuvC nuclease activity null mutant (D10A) were identified. In accompaniment with the sgRNA, Cas9, Cas9(D10A), Cas9(H840A), and Cas9(D10A, H840A) can be used to achieve double strand breakage, complementary strand breakage, non-complementary strand breakage, and no breakage on-target site, respectively. Based on such unique characteristics, many engineered enzyme activities, such as DNA methylation, histone methylation, histone acetylation, cytidine deamination, adenine deamination, and primer-directed mutation, could be introduced within or around the target site. In order to prevent off-targeting by the lasting expression of Cas9 derivatives, a lot of transient expression methods, including the direct delivery of Cas9-sgRNA riboprotein, were developed. The issue of biosafety is indispensable in in vivo applications; Cas9-sgRNA packaged into virus-like particles or extracellular vesicles have been designed and some in vivo therapeutic trials have been reported.


Assuntos
Proteína 9 Associada à CRISPR/genética , Sistemas CRISPR-Cas/genética , Edição de Genes/tendências , Genoma/genética , Sequência de Aminoácidos/genética , Animais , DNA/genética , Edição de Genes/instrumentação , Humanos , Mutação/genética , RNA Guia de Cinetoplastídeos/genética
3.
Zhongguo Zhong Yao Za Zhi ; 43(13): 2697-2704, 2018 Jul.
Artigo em Zh | MEDLINE | ID: mdl-30111019

RESUMO

With total flavonoid content and dry extract yield as the observation indexes, the optimal extraction conditions of Moringa oleifera leaves were determined by using single factor test and orthogonal test, and cyclophosphamide modeling method was used to establish immunosuppressed mice models, so as to investigate the effects of M. oleifera leaves extract on immune regulation in mice. The results showed that the optimal preparation conditions were as follows: extraction with 70% ethanol, material-liquid ratio 1:15, extraction temperature 80 °C, three times, 1.5 hours for each time. Under these conditions, the content of total flavonoids from M. oleifera leaves was 15.64 mg·g⁻¹, which can significantly enhance macrophage phagocytosis and immune organ index, promote the synthesis of serum immunoglobulin IgG and hemolysin, and decrease AST activity, with regulation effect on immune dysfunction.


Assuntos
Moringa oleifera , Animais , Antioxidantes , Flavonoides , Camundongos , Extratos Vegetais , Folhas de Planta
4.
Hum Brain Mapp ; 36(4): 1567-84, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25594281

RESUMO

Parkinson's disease (PD) is a neurodegenerative disorder associated with the striatum. Previous studies indicated that subdivisions of the striatum with distinct functional connectivity profiles contribute to different pathogeneses in PD. Segregated structural covariance (SC) pattern between the striatum and neocortex observed in healthy subjects, however, remain unknown in PD. The purpose of this study is to map and compare the subregional striatal SC network organization between 30 healthy controls and 48 PD patients and to investigate their association with the disease severity. The striatal SC network was statistically inferred by correlating the mean gray matter (GM) volume of six striatal subdivisions (including the bilateral dorsal caudate, superior ventral striatum, inferior ventral striatum, dorsal caudal putamen, dorsal rostral putamen, and ventral rostral putamen) with the entire neocortical GM volume in voxel-wise manner. The PD patients revealed marked atrophy in the striatum, cerebellum, and extra-striatum neocortices. As predicted, segregated striatal SC network patterns were observed in both groups. This suggests that in PD, pathological processes occurring in the striatum affect the same striato-cortical networks that covary with the striatum in healthy brains. The PD patients further demonstrated atypical striatal SC patterns between the caudate, parahippocampus temporal cortices, and cerebellum, which corresponded to dopaminergic associated network. The areas with significant group differences in SC were further associated with disease severity. Our findings support previous studies indicating that PD is associated with altered striato-cortical networks, and suggest that structural changes in the striatum may result in a cascade of alterations in multiple neocortices.


Assuntos
Corpo Estriado/patologia , Doença de Parkinson/patologia , Atrofia , Feminino , Lateralidade Funcional , Substância Cinzenta/patologia , Humanos , Processamento de Imagem Assistida por Computador , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neocórtex/patologia , Vias Neurais/patologia , Tamanho do Órgão , Estudos Prospectivos , Índice de Gravidade de Doença
5.
BMC Infect Dis ; 15: 279, 2015 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-26198732

RESUMO

BACKGROUND: Chronic neuropsychological sequelae may occur in patients with tuberculous meningitis (TBM). The impact of structural abnormalities on the clinical performance of patients with TBM is unknown. This study applied the Diffeomorphic Anatomical Registration Through Exponentiated Lie Algebra (DARTEL) voxel-based morphometry (VBM) to determine if gray matter deficits in TBM are associated with acute presentations and chronic cognitive impairment. METHODS: Seventeen patients with TBM who discontinued their anti-TB therapy for more than six months, and 17 age-, sex-, and education-matched healthy subjects were enrolled. Differences in gray matter volume (GMV) between patients and healthy controls were investigated using DARTEL-VBM to determine structural abnormalities. Disease severity during the acute stage was scored by clinical profiles and conventional imaging findings. Correlations among chronic structural deficits, cognitive impairment, and initial disease severity were assessed. RESULTS: The patients with TBM had worse neuropsychological subtest performances than the healthy controls. Compared to the controls, the patients showed smaller GMVs in the right thalamus, right caudate nucleus, right superior and middle temporal gyrus, right precuneus, and left putamen (p < 0.001). The smaller GMVs in the right thalamus, right superior temporal gyrus, right precuneus, left putamen, and right caudate nucleus (p < 0.05) were further associated with worse cognitive function. More severe initial disease also correlated with smaller GMVs in the right caudate nucleus (p < 0.05). CONCLUSION: Multiple domain cognitive impairment may persist in patients with chronic TBM even after appropriate treatment. Worse initial disease severity may contribute to the vulnerability of brain tissue to damage, with subsequent neuropsychological consequences.


Assuntos
Transtornos Cognitivos/diagnóstico , Substância Cinzenta/fisiopatologia , Tuberculose Meníngea/patologia , Doença Aguda , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Cognição , Transtornos Cognitivos/etiologia , Feminino , Substância Cinzenta/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Radiografia , Índice de Gravidade de Doença , Tuberculose Meníngea/complicações , Adulto Jovem
6.
Opt Express ; 22 Suppl 7: A1695-700, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25607483

RESUMO

Aluminum zinc oxide (AZO) has been embedded onto indium tin oxide (ITO) anode to enhance the light extraction from an organic light-emitting diode (OLED). The embedded AZO provides deflection and scattering interfaces on the newly generated AZO/organics and AZO/ITO interfaces rather than the conventional ITO/organic interface. The current efficiency of AZO embedded OLEDs was enhanced by up to 64%, attributed to the improved light extraction by additionally created reflection and scattering of emitted light on the AZO/ITO interfaces which was roughed in AZO embedding process. The current efficiency was found to increase with the increasing AZO embedded area ratio, but limited by the accompanying increases in haze and electrical resistance of the AZO embedded ITO film.

7.
Digit Health ; 10: 20552076241257014, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38778867

RESUMO

Background: Vaginal birth after cesarean (VBAC) is generally regarded as a safe and viable birthing option for most women with prior cesarean delivery. Nonetheless, concerns about heightened risks of adverse maternal and perinatal outcomes have often dissuaded women from considering VBAC. This study aimed to assess the performance of an artificial intelligence (AI)-powered VBAC prediction system integrated into a decision-aid birth choice platform for shared decision-making (SDM). Materials and Methods: Employing a retrospective design, we collected medical records from a regional hospital in northern Taiwan from January 2019 to May 2023. To explore a suitable model for tabular data, we compared two prevailing modeling approaches: tree-based models and logistic regression models. We subjected the tree-based algorithm, CatBoost, to binary classification. Results: Forty pregnant women with 347 records were included. The CatBoost model demonstrated a robust performance, boasting an accuracy rate of 0.91 (95% confidence interval (CI): 0.86-0.94) and an area under the curve of 0.89 (95% CI: 0.86-0.93), surpassing both regression models and other boosting techniques. CatBoost captured the data characteristics on the significant impact of gravidity and the positive influence of previous vaginal birth, reinforcing established clinical guidelines, as substantiated by the SHapley Additive exPlanations analysis. Conclusion: Using AI techniques offers a more accurate assessment of VBAC risks, boosting women's confidence in selecting VBAC as a viable birthing option. The seamless integration of AI prediction systems with SDM platforms holds a promising potential for enhancing the effectiveness of clinical applications in the domain of women's healthcare.

8.
Guang Pu Xue Yu Guang Pu Fen Xi ; 32(4): 1114-7, 2012 Apr.
Artigo em Zh | MEDLINE | ID: mdl-22715797

RESUMO

Nitrogen-doped carbon supported cobalt electrocatalysts for the reduction of oxygen were prepared from the high nitrogen content prepolymer of melamine formaldehyde resin and cobalt acetate. The preparation and structure of the electrocatalysts were investigated by TG-FTIR and XRD spectroscopic analysis methods. The electrochemical reduction of oxygen was studied at the nitrogen-doped carbon supported cobalt by using the rotating disk electrode method. The results indicated that the catalyst structure changed with the carbonization temperature under the protection of the inert gases. Some organic groups were decomposed into CO, CO2, HCHO, NH3 and NO2, which were taken away by the protecting gas. The electrocatalysts exhibited face-centered cubic structure. The RDE results showed that good electrocatalytic activity for oxygen reduction at these electrocatalysts was found under the experimental condition. The onset potential for oxygen reduction (E(onset)) was 0.5 V (vs. SCE). The catalyst prepared under 700 C was found to have the highest activity.

9.
Sci Rep ; 12(1): 13745, 2022 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-35962029

RESUMO

A bidirectional DC-DC converter is required for an energy storage system. High efficiency and a high step-up and step-down conversion ratio are the development trends. In this research, a series of bidirectional high-gain Cuk circuits was derived by combining tapped inductors and bidirectional Cuk. After analyzing and comparing the characteristics of each circuit, a bidirectional high-gain Cuk circuit with a tapped-inductor (reverse coupling) was proposed. The proposed converter has a simple structure and a high voltage gain in both the step-down (Buck) and step-up (Boost) operation modes. The voltage stress of S2 was low. The voltage stress of S1 was high, however, and this is a disadvantage of the proposed converter. The proposed circuit's characteristics were thoroughly examined, including the voltage gain characteristics and the design of the main parameters. We established a power loss model of the new topology, and the tapped-inductor turn ratio was optimized for high efficiency. Finally, a 400 W experimental implementation of the converter was shown to achieve efficiencies of 93.5% and 92.4% in the step-up and step-down modes, respectively. These findings verified the validity of the proposed circuit's theoretical analysis.

10.
Int J Exp Pathol ; 92(2): 97-105, 2011 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21070402

RESUMO

The cancer-initiating capacity of most malignant tumours is considered to reside in a small subpopulation of cells. Therapeutical interventions should target these cells rather than the tumour mass. Numerous studies have shown that the carbohydrate antigen structure CD176 (Thomsen-Friedenreich antigen, core-1) is present in many types of cancer and absent in normal adult human tissues. In this study, we assessed whether CD176 is co-expressed with CD44 or CD133 [markers of cancer-initiating cells (CIC)] in human lung, breast and liver carcinoma. A variety of human cancer cell lines and surgical specimens of these malignancies were examined. It was found that in most cases the majority of tumour cells stained strongly for CD44 by immunohistochemistry and flow cytometry, whereas CD133 expression was found on a smaller, but varying proportion of cells. Co-expression of CD176 with CD44 was found at a surprisingly high percentage of cancer cells in vitro and in vivo. Co-expression of CD176 with CD133 was also detected, although at a lower rate. Tamoxifen treatment of MDA-435 breast cancer cells enhanced the CD44(+) /CD176(+) phenotype. Evidence is provided through a new sandwich solid-phase enzyme-linked immunosorbent assay (ELISA) suggesting that CD44 is a carrier molecule for CD176 not only in colorectal cancer as previously reported, but also in lung, breast and liver cancer. The expression of CD176 in CIC suggests that it may represent an effective target for tumour therapies.


Assuntos
Antígenos Glicosídicos Associados a Tumores/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Pulmonares/metabolismo , Células-Tronco Neoplásicas/metabolismo , Antígeno AC133 , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Antígenos CD/metabolismo , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Contagem de Células , Linhagem Celular Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral/metabolismo , Linhagem Celular Tumoral/patologia , Feminino , Citometria de Fluxo , Proteínas Ligadas por GPI , Glicoproteínas/metabolismo , Humanos , Receptores de Hialuronatos/metabolismo , Imuno-Histoquímica , Isoantígenos , Neoplasias Hepáticas/patologia , Neoplasias Pulmonares/patologia , Células-Tronco Neoplásicas/patologia , Peptídeos/metabolismo , Receptores de Superfície Celular , Tamoxifeno/farmacologia
11.
Biomolecules ; 11(3)2021 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-33804101

RESUMO

Emerging evidence has shown the oncogenic roles of leptin in modulating cancer progression in addition to its original roles. Analyses of transcriptomic data and patients' clinical information have revealed leptin's prognostic significance in renal cell carcinoma (RCC). However, its biological effects on RCC progression have not yet been explored. Clinical and transcriptomic data of a RCC cohort of 603 patients were retrieved from The Cancer Genome Atlas (TCGA) and analyzed to reveal the correlation of leptin with clinical outcomes and the hierarchical clustering of gene signatures based on leptin levels. In addition, cox univariate and multivariate regression analyses, cell migration upon leptin treatment, identification of putative leptin-regulated canonical pathways via ingenuity pathway analysis (IPA), and the investigation of induction of Wnt5a, ROR2, and Jun N-terminal Kinases (JNK) phosphorylation activation were performed. We first observed a correlation of high leptin levels and poor outcomes in RCC patients. Knowledge-based analysis by IPA indicated the induction of cancer cell migration by leptin, which was manifested via direct leptin treatment in the RCC cell lines. In RCC patients with high leptin levels, the planar cell polarity (PCP)/JNK signaling pathway was shown to be activated, and genes in the axis, including CTHRC1, FZD2, FZD10, ROR2, WNT2, WNT4, WNT10B, WNT5A, WNT5B, and WNT7B, were upregulated. All of these genes were associated with unfavorable clinical outcomes. WNT5A and ROR2 are pivotal upstream regulators of PCP/JNK signaling, and their correlations with leptin expression levels were displayed by a Pearson correlation analysis. The inhibition of signal transduction by SP600125 reversed leptin-mediated cell migration properties in RCC cell lines. The results indicate the prognostic impact of leptin on RCC patients and uncover its ability to promote cell migration via PCP/JNK signaling.


Assuntos
Carcinoma de Células Renais/patologia , Progressão da Doença , Neoplasias Renais/patologia , Leptina/farmacologia , Carcinoma de Células Renais/genética , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Polaridade Celular/efeitos dos fármacos , Análise por Conglomerados , Estudos de Coortes , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Renais/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Análise Multivariada , Metástase Neoplásica , Prognóstico , Análise de Regressão , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/genética , Resultado do Tratamento
12.
Guang Pu Xue Yu Guang Pu Fen Xi ; 30(8): 2103-6, 2010 Aug.
Artigo em Zh | MEDLINE | ID: mdl-20939316

RESUMO

The Cu1Zr1Ce9Odelta catalysts synthesized with coprecipitation method were used into the selective CO oxidation in hydrogen-rich gas. The adsorbed species and the intermediates on Cu1Zr1Ce9Odelta catalysts were examined by in-situ diffuse reflectance FTIR spectroscopy (in-situ DRIFTS) technique. It was found that hydrogen, oxygen and CO in the feed stream were adsorbed competitively at the same adsorption sites on the surface of Cu1Zr1Ce9Odelta catalysts. The pretreatment with hydrogen caused the deep reduction of Cu+ species to Cu0 species and decreased the capacity of CO adsorption on the catalyst surface. The Cu1Zr1Ce9Odelta catalyst pretreated with oxygen offered more active oxygen species and inhibited the deep reduction of Cu+ species. The helium pretreatment only purified the surface of Cu1Zr1Ce9Odelta catalyst. Two IR bands at 2938.7 and 2843.8 cm(-1) due to bridged formate and bidentate formate species appeared at 180 degrees C. The active oxygen anion of Cu1Zr1Ce9Odelta catalyst could react with CO and produce carbonate species at room temperatures. The carbonate and formate species occupied the adsorption sites and deteriorated the catalytic performance of Cu1Zr1Ce9Odelta. Flushing the Cu1ZnrCe9Odelta catalyst with helium at 300 degrees C, the bidentate formate species on the catalyst surface decomposed to monodentate carbonate species and then further decomposed to CO2, which could release the adsorption sites and restore well the catalytic activity.

13.
Guang Pu Xue Yu Guang Pu Fen Xi ; 30(3): 672-6, 2010 Mar.
Artigo em Zh | MEDLINE | ID: mdl-20496684

RESUMO

CuO-CeO2 series catalysts are the effective catalysts for the selective CO oxidation in hydrogen-rich gas. The adsorption species on the CuO-CeO2 catalysts doped with alkali and alkaline earth metal oxides were investigated with in situ diffuse reflectance FTIR spectroscopy (in-situ DRIFTS) technique. The results showed that a bane at 2 106 cm(-1), due to the carbonyl species, appeared on the CuO-CeO2 catalysts. In the reaction atmosphere, the intensity of this band increased first and then decreased with increasing the temperatures. It was noted that the main active adsorption sites of the CuO-CeO2 catalysts were Cu+ species. At lower temperatures, the carbonyl species were desorbed from the surface of CuO-CeO2 catalysts in the reversible form, while they were desorbed mainly in the irreversible form at the higher temperatures. A sharp peak at 3 660 cm(-1), attributed to the geminal Ce(OH)2 group, was also apparent on the surface of reduced CuO-CeO2 catalyst. The peaks at 1 568, 2 838 and 2 948 cm(-1) were attributed to formate species and the peaks centered at 1 257 and 1 633 cm(-1) were assigned to carbonate species. CO could react with the active hydroxyl species and generate formate species. At higher temperatures, the C-H bond of formate species could break and form carbonate species. These two species would decrease the performance of CuO-CeO2 catalysts at higher temperatures. The stronger IR peaks attributed to CO2 and formate species were observed, moreover there was still a weak IR peak assigned to carbonyl species for Cu1 Li1 Ce9Odelta catalyst when the temperature was above 180 degrees C. It was shown that as the electron donor, the doping of Li2 O on CuO-CeO2 catalyst could contribute to the irreversible desorption of CO at lower temperatures and inhibit the adsorption of H2 on the catalytic surface, and benefit the formation of formate species as well. Although the amounts of CO adsorption on Cu1 Mg1 Ce9 Odelta and Cu1 Ba1 Ce9 Odelta catalysts were much more than other catalysts at lower temperatures, they were mainly desorbed in the reversible form, which had no contribution to the selective CO oxidation.

14.
Guang Pu Xue Yu Guang Pu Fen Xi ; 29(3): 840-3, 2009 Mar.
Artigo em Zh | MEDLINE | ID: mdl-19455839

RESUMO

Carbon nanotubes (CNTs) supported platinum electrocatalyst Pt/CNTs with high dispersion were prepared by a modified ethylene glycol method with sodium dodecyl sulfate (SDS) as the stabilizer. UV-Vis, FTIR and XRD spectroscopic analysis methods were used to study the preparation of the electrocatalysts, and the effect of the SDS addition to the ethylene glycol solution on the structure as well as the electrocatalytic activity of the Pt/CNTs electrocatalysts were also investigated. The results showed that PtCl6(2-) could form a complex compound with SDS, and all PtCl6(2-) were completely reduced by ethylene glycol; oxygen containing groups were produced on the surface of CNTs to facilitate the Pt nanoparticle absorption, and no SDS remained on the electrocatalysts; the Pt/CNTs electrocatalysts exhibited face-centered cubic structure; the particle size of Pt/CNTs-2 catalyst prepared by SDS addition was about 4. 5 nm. The CV test results showed that the Pt/CNTs-2 catalyst showed higher methanol electro-oxidation activity compared with Pt/CNTs-1 prepared by traditional ethylene glycol reduction method.

15.
Cancers (Basel) ; 11(3)2019 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-30836712

RESUMO

Ghrelin is a peptide hormone, originally identified from the stomach, that functions as an endogenous ligand of the growth hormone secretagogue receptor (GHSR) and promotes growth hormone (GH) release and food intake. Increasing reports point out ghrelin's role in cancer progression. We previously characterized ghrelin's prognostic significance in the clear cell subtype of renal cell carcinoma (ccRCC), and its pro-metastatic ability via Snail-dependent cell migration. However, ghrelin's activity in promoting cell invasion remains obscure. In this study, an Ingenuity Pathway Analysis (IPA)-based investigation of differentially expressed genes in Cancer Cell Line Encyclopedia (CCLE) dataset indicated the potential association of Aurora A with ghrelin in ccRCC metastasis. In addition, a significant correlation between ghrelin and Aurora A expression level in 15 ccRCC cell line was confirmed by variant probes. ccRCC patients with high ghrelin and Aurora A status were clinically associated with poor outcome. We further observed that ghrelin upregulated Aurora A at the protein and RNA levels and that ghrelin-induced ccRCC in vitro invasion and in vivo metastasis occurred in an Aurora A-dependent manner. Furthermore, MMP1, 2, 9 and 10 expressions are associated with poor outcome. In particular, MMP10 is significantly upregulated and required for the ghrelin-Aurora A axis to promote ccRCC invasion. The results of this study indicated a novel signaling mechanism in ccRCC metastasis.

16.
J Clin Invest ; 129(8): 3347-3360, 2019 05 21.
Artigo em Inglês | MEDLINE | ID: mdl-31112529

RESUMO

PD-L1 is a promising therapeutic target in aggressive cancers. However, immune landscapes and cancer hallmarks of human PD-L1+ tumors, as well as their roles in determining therapeutic efficacies are unknown. Here we identified, in detailed studies of gene data regarding 9769 patients of 32 types of human cancers, that PD-L1 could not exclusively represent IFN-γ signature and potentially signified pro-inflammatory myeloid responses in a tumor. PD-L1 heterogeneity endowed by local immune landscapes controlled cancer hallmarks and clinical outcomes of patients. Mechanically, NF-κB signal elicited by macrophage inflammatory responses generated PD-L1+ cancer cells exhibiting capabilities to aggressively survive, support angiogenesis, and metastasize, whereas STAT1 signal triggered by activated T cells induced PD-L1+ cancer cells susceptive to apoptosis. Importantly, PD-L1+ cancer cells generated by macrophages established great resistance to conventional chemotherapy, cytotoxicity of tumor-specific effector T cells, and therapy of immune checkpoint blockade. Therapeutic strategy combining immune checkpoint blockade with macrophage depletion or NF-κB inhibition in vivo effectively and successfully elicited caner regression. Our results provide insight into the functional features of PD-L1+ tumors and suggest that strategies to influence functional activities of inflammatory cells may benefit immune checkpoint blockade therapy.


Assuntos
Antígeno B7-H1/imunologia , Imunoterapia , Macrófagos/imunologia , Proteínas de Neoplasias/imunologia , Neoplasias , Linfócitos T , Adolescente , Adulto , Idoso , Animais , Feminino , Células Hep G2 , Humanos , Macrófagos/patologia , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/patologia , Neoplasias/terapia , Linfócitos T/imunologia , Linfócitos T/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
17.
Quant Imaging Med Surg ; 9(6): 1126-1131, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31367567

RESUMO

Hepatic granulomas caused by nontuberculous mycobacteria (NTM) are an uncommon, insidious, and indolent disease. Making an accurate diagnosis of a hepatic nontuberculous granuloma is challenging because of nonspecific clinical presentations and radiological appearances, especially in patients with a history of malignant tumors, as these lesions may mimic metastases and make a dilemma for decision-making in treatment. Herein, we report three cases of hepatic nontuberculous granulomas following operations for malignant tumors, including colon cancer, ovarian adenocarcinoma, and both rectal and renal carcinoma, respectively. Two patients presented with multiple hepatic lesions and the third had a solitary nodule in the liver. Computed tomography (CT) showed low attenuating nodules without early enhancement in the arterial phase but a slight peripheral enhancement in the portal venous phase after the intravenous administration of contrast agent. Magnetic resonance imaging (MRI) showed high signal intensity on T2-weighted image, rim enhancement in the venous phase and no contrast agent of Gd-EOB-DTPA uptake in the hepatobiliary phase. The biopsy was performed, and histopathological examinations revealed the chronic granulomas composed of epithelioid histiocytes, inflammatory cells, and Langhans giant cells. The results of nested polymerase chain reaction (PCR) were positive for NTM.

18.
Cancer Imaging ; 19(1): 51, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337425

RESUMO

BACKGROUND: Computed tomography (CT)-guided pulmonary core biopsies of small pulmonary nodules less than 15 millimeters (mm) are challenging for radiologists, and their diagnostic accuracy has been shown to be variable in previous studies. Common complications after the procedure include pneumothorax and pulmonary hemorrhage. The present study compared the diagnostic accuracy of small and large lesions using CT-guided core biopsies and identified the risk factors associated with post-procedure complications. METHODS: Between January 1, 2016, and December 31, 2017, 198 CT-guided core biopsies performed on 195 patients at our institution were retrospectively enrolled. The lesions were separated into group A (< or = 15 mm) and group B (> 15 mm) according to the longest diameter of the target lesions on CT. Seventeen-gauge introducer needles and 18-gauge automated biopsy instruments were coaxially used for the biopsy procedures. The accuracy and complications, including pneumothorax and pulmonary hemorrhage, of the procedures of each group were recorded. The risk factors for pneumothorax and pulmonary hemorrhage were determined using univariate analysis of variables. RESULTS: The diagnostic accuracies of group A (n = 43) and group B (n = 155) were 83.7 % and 96.8 %, respectively (p = 0.005). The risk factors associated with post-biopsy pneumothorax were longer needle path length from the pleura to the lesion (p = 0.020), lesion location in lower lobes (p = 0.002), and patients with obstructive lung function tests (p = 0.034). The risk factors associated with post-biopsy pulmonary hemorrhage were longer needle path length from the pleura to the lesion (p < 0.001), smaller lesions (p < 0.001), non-pleural contact lesions (p < 0.001), patients without restrictive lung function tests (p = 0.034), and patients in supine positions (p < 0.003). CONCLUSION: CT-guided biopsies of small nodules equal to or less than 15 mm using 17-gauge guiding needles and 18-gauge biopsy guns were accurate and safe. The biopsy results of small lesions were less accurate than those of large lesions, but the results were a reliable reference for clinical decision-making. Understanding the risk factors associated with the complications of CT-guided biopsies is necessary for pre-procedural planning and communication.


Assuntos
Neoplasias Pulmonares/patologia , Nódulos Pulmonares Múltiplos/patologia , Pneumotórax/etiologia , Hemorragia Pós-Operatória/etiologia , Adulto , Idoso , Feminino , Humanos , Biópsia Guiada por Imagem/efeitos adversos , Biópsia Guiada por Imagem/normas , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Pneumotórax/epidemiologia , Hemorragia Pós-Operatória/epidemiologia , Reprodutibilidade dos Testes , Tomografia Computadorizada por Raios X
20.
Medicine (Baltimore) ; 97(48): e13392, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30508937

RESUMO

To explore the role of quantitative digital subtraction angiography (QDSA) in the diagnosis of small hepatocellular carcinoma (HCC).Between November 2015 and November 2017, all patients who underwent chemoembolization for HCC were retrospectively reviewed. Patients with tumors measuring more than 5 cm or evident post-processing imaging artifacts were excluded. Images were post-processed using the QDSA technique. Regions of interest were manually drawn on proper hepatic artery (as a reference), target HCC and peritumoral liver. Time-concentration curves and flow parameters of the peak ratio, subtracted time-to-peak (TTP), and area under the curve (AUC) ratio was obtained and analyzed.A total of 146 HCCs (mean diameter, 1.6 cm) of 71 cirrhotic patients (54 men, 17 women; mean age, 67.7 years) were enrolled. Compared with liver parenchyma, HCCs showed an increased and more rapid flow (peak ratio, AUC ratio, subtracted TTP, and wash-in slope; all P <.001). Compared with untreated HCCs, chemoembolized HCCs showed a slower flow (subtracted TTP and wash-in slope, P = .004 and .002, respectively). HCCs with a typical enhancement pattern on computed tomography (CT) or magnetic resonance imaging (MRI) had a trend toward Type III (washout pattern) time-concentration curves (P <.001). Chemoembolized HCCs had a trend toward Type II (plateau pattern) time-concentration curves (P = .005).QDSA technology can be used to quantify perfusion measurements of HCC and hepatic parenchyma and to assess perfusion changes after HCC chemoembolization.


Assuntos
Angiografia Digital/métodos , Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Idoso , Área Sob a Curva , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/terapia , Quimioembolização Terapêutica , Feminino , Humanos , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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