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1.
J Biomed Opt ; 29(7): 076004, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39035576

RESUMO

Significance: Frequency-domain diffuse optical tomography (FD-DOT) could enhance clinical breast tumor characterization. However, conventional diffuse optical tomography (DOT) image reconstruction algorithms require case-by-case expert tuning and are too computationally intensive to provide feedback during a scan. Deep learning (DL) algorithms front-load computational and tuning costs, enabling high-speed, high-fidelity FD-DOT. Aim: We aim to demonstrate a simultaneous reconstruction of three-dimensional absorption and reduced scattering coefficients using DL-FD-DOT, with a view toward real-time imaging with a handheld probe. Approach: A DL model was trained to solve the DOT inverse problem using a realistically simulated FD-DOT dataset emulating a handheld probe for human breast imaging and tested using both synthetic and experimental data. Results: Over a test set of 300 simulated tissue phantoms for absorption and scattering reconstructions, the DL-DOT model reduced the root mean square error by 12 % ± 40 % and 23 % ± 40 % , increased the spatial similarity by 17 % ± 17 % and 9 % ± 15 % , increased the anomaly contrast accuracy by 9 % ± 9 % ( µ a ), and reduced the crosstalk by 5 % ± 18 % and 7 % ± 11 % , respectively, compared with model-based tomography. The average reconstruction time was reduced from 3.8 min to 0.02 s for a single reconstruction. The model was successfully verified using two tumor-emulating optical phantoms. Conclusions: There is clinical potential for real-time functional imaging of human breast tissue using DL and FD-DOT.


Assuntos
Algoritmos , Neoplasias da Mama , Aprendizado Profundo , Processamento de Imagem Assistida por Computador , Imagens de Fantasmas , Tomografia Óptica , Tomografia Óptica/métodos , Tomografia Óptica/instrumentação , Humanos , Processamento de Imagem Assistida por Computador/métodos , Neoplasias da Mama/diagnóstico por imagem , Mama/diagnóstico por imagem , Feminino , Imageamento Tridimensional/métodos
2.
ACS Nano ; 18(29): 19354-19368, 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-38975953

RESUMO

Tumor-stromal interactions and stromal heterogeneity in the tumor microenvironment are critical factors that influence the progression, metastasis, and chemoresistance of pancreatic ductal adenocarcinoma (PDAC). Here, we used spatial transcriptome technology to profile the gene expression landscape of primary PDAC and liver metastatic PDAC after bioactive black phosphorus nanomaterial (bioactive BP) treatment using a murine model of PDAC (LSL-KrasG12D/+; LSL-Trp53R172H/+; and Pdx-1-Cre mice). Bioinformatic and biochemical analyses showed that bioactive BP contributes to the tumor-stromal interplay by suppressing cancer-associated fibroblast (CAF) activation. Our results showed that bioactive BP contributes to CAF heterogeneity by decreasing the amount of inflammatory CAFs and myofibroblastic CAFs, two CAF subpopulations. Our study demonstrates the influence of bioactive BP on tumor-stromal interactions and CAF heterogeneity and suggests bioactive BP as a potential PDAC treatment.


Assuntos
Fibroblastos Associados a Câncer , Carcinoma Ductal Pancreático , Nanoestruturas , Neoplasias Pancreáticas , Fósforo , Animais , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Camundongos , Nanoestruturas/química , Fósforo/química , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Fibroblastos Associados a Câncer/efeitos dos fármacos , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/metabolismo , Microambiente Tumoral/efeitos dos fármacos , Humanos , Linhagem Celular Tumoral
3.
Bioorg Chem ; 144: 107175, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38335757

RESUMO

Eight undescribed (1-8) and 46 known compounds (9-54) were isolated from the deep-sea-derived Aspergillus sp. MCCC 3A00392. Compounds 1-3 were three novel oxoindolo diterpenoids, 4-6 were three bisabolane sesquiterpenoids, while 7 and 8 were two monocyclic cyclopropanes. Their structures were established by exhaustive analyses of the HRESIMS, NMR, and theoretical calculations of the NMR data and ECD spectra. Compounds 10, 33, 38, and 39 were able to inhibit tumor necrosis factor (TNF)-induced necroptosis in murine L929 cell lines. Functional experiments verified that compounds 10 and 39 inhibited necroptosis by downregulating the phosphorylation of RIPK3 and MLKL. Moreover, compound 39 also reduced the phosphorylation of RIPK1. Compounds 10, 33, and 34 displayed potent inhibitory activities against RSL-3 induced ferroptosis with the EC50 value of 3.0 µM, 0.4 µM, and 0.1 µM, respectively. Compound 10 inhibited ferroptosis by the downregulation of HMOX1, while compounds 33 and 34 inhibited ferroptosis through regulation of NRF2/SLC7A11/GCLM axis. However, these compounds only showed weak effect in either the necroptosis or ferroptosis relative mouse disease models. Further studies of pharmacokinetics and pharmacodynamics might improve their in vivo bioactivities.


Assuntos
Ferroptose , Sesquiterpenos , Camundongos , Animais , Necroptose , Aspergillus/química , Sesquiterpenos/química , Sesquiterpenos Monocíclicos
4.
J Agric Food Chem ; 72(10): 5463-5476, 2024 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-38414429

RESUMO

The prevalence of food allergies has grown dramatically over the past decade. Recently, studies have shown the potential of marine substances to alleviate food allergies. We utilized a rat basophilic leukemia (RBL)-2H3 model to evaluate the antiallergic effects of alternariol monomethyl ether (AME) extracted from marine fungi Alternaria sp. Our results showed that AME attenuated food allergy symptoms in mice and reduced histamine release in serum. The population of mast cells in the spleen and mesenteric lymph nodes was considerably reduced. Moreover, in vitro assays also revealed that AME inhibited the release of ß-hexosaminidase and histamine. Transcriptomic analysis uncovered that AME regulated gene expression associated with mast cells. Additionally, Western blotting demonstrated that AME suppressed mast cell activation by modulating MAPK and NF-κB signaling pathways. Taken together, these findings provide a theoretical basis for the potential antiallergic use of marine-derived compounds in the development of functional foods.


Assuntos
Antialérgicos , Hipersensibilidade Alimentar , Lactonas , Ratos , Camundongos , Animais , NF-kappa B/metabolismo , Ovalbumina/metabolismo , Mastócitos , Transdução de Sinais , Antialérgicos/farmacologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-38284738

RESUMO

Ferroptosis is a newly discovered form of programmed cell death characterized by iron overload, ROS accumulation, and lipid peroxidation. It is distinguished by unique morphological, biochemical, and genetic features and stands apart from other known regulated cell death mechanisms. Studies have demonstrated a close association between ferroptosis and various cancers, including liver cancer, lung cancer, renal cell carcinoma, colorectal cancer, pancreatic cancer, and ovarian cancer. Inducing ferroptosis has shown promising results in inhibiting tumor growth and reversing tumor progression. However, the challenge lies in regulating ferroptosis in vivo due to the scarcity of potent compounds that can activate it. Integrating emerging biomedical discoveries and technological innovations with conventional therapies is imperative. Notably, considerable progress has been made in cancer treatment by leveraging immunotherapy and nanotechnology to trigger ferroptosis. This review explores the relationship between ferroptosis and emerging immunotherapies and nanotechnologies, along with their potential underlying mechanisms, offering valuable insights for developing novel cancer treatment strategies.

6.
Ultrasonography ; 43(1): 68-77, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38109892

RESUMO

PURPOSE: This study evaluated the value of contrast-enhanced ultrasonography (CEUS) in the ultrasound-guided microwave ablation (MWA) treatment of symptomatic focal uterine adenomyosis. METHODS: This retrospective study was conducted between March 2020 and January 2023, enrolling 52 patients with symptomatic focal uterine adenomyosis who had undergone MWA. All patients were examined with CEUS before and after MWA. The non-perfused volume (NPV) was compared between CEUS and dynamic contrast-enhanced magnetic resonance imaging (DCEMRI) following ablation. Therapeutic efficacy and safety were evaluated at 3-, 6-, and 12-month follow-ups. Additionally, this study explored the correlations between pre-treatment CEUS features and a volume reduction ratio indicating sufficient ablation, defined as 50% or more at the 3-month follow-up. RESULTS: No significant differences in NPV were noted between CEUS and DCE-MRI immediately after MWA and during follow-up (all P>0.05). At the 3-month follow-up, the median VRRs for the uterus and adenomyosis were 33.2% and 63.9%, respectively. Sufficient ablation was achieved in 69.2% (36/52) of adenomyosis cases, while partial ablation was observed in the remaining 30.8% (16/52). The identification of non-enhancing areas on pre-treatment CEUS was associated with sufficient ablation (P=0.016). At the 12-month follow-up, significant decreases were observed in both the uterine and adenomyosis volumes (all P<0.001). Dysmenorrhea and menorrhagia were significantly alleviated at 12 months, and no major complications were encountered. CONCLUSION: CEUS can be used to evaluate the ablation zone of focal adenomyosis that has been treated with MWA, similarly to DCE-MRI. The identification of non-enhancing areas on pretreatment CEUS indicates satisfactory treatment outcomes.

7.
Mar Drugs ; 21(11)2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37999419

RESUMO

A systematic investigation combined with a Global Natural Products Social (GNPS) molecular networking approach, was conducted on the metabolites of the deep-sea-derived fungus Samsoniella hepiali W7, leading to the isolation of three new fusaric acid derivatives, hepialiamides A-C (1-3) and one novel hybrid polyketide hepialide (4), together with 18 known miscellaneous compounds (5-22). The structures of the new compounds were elucidated through detailed spectroscopic analysis. as well as TD-DFT-based ECD calculation. All isolates were tested for anti-inflammatory activity in vitro. Under a concentration of 1 µM, compounds 8, 11, 13, 21, and 22 showed potent inhibitory activity against nitric oxide production in lipopolysaccharide (LPS)-activated BV-2 microglia cells, with inhibition rates of 34.2%, 30.7%, 32.9%, 38.6%, and 58.2%, respectively. Of particularly note is compound 22, which exhibited the most remarkable inhibitory activity, with an IC50 value of 426.2 nM.


Assuntos
Ácido Fusárico , Paecilomyces , Ácido Fusárico/farmacologia , Macrófagos , Anti-Inflamatórios , Estrutura Molecular
8.
Chem Biodivers ; 20(11): e202301507, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37847218

RESUMO

One new alkaloid, (S)-2-acetamido-4-(2-(methylamino)phenyl)-4-oxobutanoic acid (1), was isolated from the deep-sea-derived Penicillium citrinum XIA-16, together with 25 known compounds including ten polyketones (2-11), eight alkaloids (12-19), six steroids (20-25), and a fatty acid (26). Their planar and relative structures were determined by an analysis of 1D and 2D nuclear magnetic resonance (NMR) as well as high resolution electrospray ionization mass spectroscopy (HR-ESI-MS) data. The absolute configuration of 1 was determined by comparison of the experimental and calculated electronic circular dichroism (ECD) spectra. Penicitrinol B (6) significantly inhibited RSL3-induced ferroptosis (EC50 =2.0 µM) by reducing lipid peroxidation and heme oxygenase 1 (HMOX1) expression. Under the concentration of 10 µM, penicitrinol A (7) was able to inhibit cuproptosis with the cell viabilities of 68.2 % compared to the negative control (copper and elesclomol) with the cell viabilities of 14.8 %.


Assuntos
Alcaloides , Antineoplásicos , Penicillium , Animais , Penicillium/química , Antineoplásicos/farmacologia , Espectroscopia de Ressonância Magnética/métodos , Alcaloides/química , Crustáceos , Estrutura Molecular
9.
Front Immunol ; 14: 1223650, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37575248

RESUMO

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant and lethal human cancers in the world due to its high metastatic potential, and patients with PDAC have a poor prognosis, yet quite little is understood regarding the underlying biological mechanisms of its high metastatic capacity. Baicalein has a dramatic anti-tumor function in the treatment of different types of cancer. However, the therapeutic effects of baicalein on human PDAC and its mechanisms of action have not been extensively understood. In order to explore the biological characteristic, molecular mechanisms, and potential clinical value of baicalein in inhibiting the metastatic capacity of PDAC. We performed several in vitro, in vivo, and in silico studies. We first examined the potential regulation of baicalein in the metastatic capacity of PDAC cells. We showed that baicalein could dramatically suppress liver metastasis of PDAC cells with highly metastatic potential in mice model. The high-throughput sequencing analysis was employed to explore the biological roles of baicalein in PDAC cells. We found that baicalein might be involved in the infiltration of Cancer-Associated Fibroblasts (CAF) in PDAC. Moreover, a baicalein-related risk model and a lncRNA-related model were built by Cox analysis according to the data set of PDAC from TCGA database which suggested a clinical value of baicalein. Finally, we revealed a potential downstream target of baicalein in PDAC, we proposed that baicalein might contribute to the infiltration of CAF via FGFBP1. Thus, we uncovered a novel role for baicalein in regulation of PDAC liver metastasis that may contribute to its anti-cancer effect. We proposed that baicalein might suppress PDAC liver metastasis via regulation of FGFBP1-mediated CAF infiltration. Our results provide a new perspective on clinical utility of baicalein and open new avenues for the inhibition of liver-metastasis of PDAC.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Hepáticas , Neoplasias Pancreáticas , Camundongos , Animais , Humanos , Prognóstico , Microambiente Tumoral , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Pancreáticas
10.
Reprod Sci ; 30(10): 2920-2931, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37204635

RESUMO

Polycystic ovary syndrome (PCOS) is a common and frequent disease and always leads endocrine and metabolic disorder among women in reproductive age. Ovary is the main organ involved in polycystic ovary syndrome, and its function impairment will lead to reproductive dysfunction. Some recent studies have demonstrated that autophagy plays an important role in the pathogenesis of PCOS, and there are many different mechanisms that affect autophagy and the occurrence of PCOS, and they provide a new direction for us to predict the mechanism of PCOS. In this review, we discuss the role of autophagy in different ovarian cells: granulosa cells, oocytes, and theca cells, and introduce the important role that they play in the progress of PCOS. The main purpose of this review is to provide the research background and some relevant suggestions for our future work in autophagy and help us better explore the pathogenesis and autophagy mechanisms of PCOS. Furthermore, it will help us gain a new insight of the pathophysiology and treatment of PCOS.


Assuntos
Síndrome do Ovário Policístico , Feminino , Humanos , Síndrome do Ovário Policístico/metabolismo , Células da Granulosa/metabolismo , Oócitos/metabolismo , Autofagia
11.
Mar Drugs ; 21(4)2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37103373

RESUMO

Two new xanthones (1 and 2) were isolated from the deep-sea-derived fungus Penicillium sp. MCCC 3A00126 along with 34 known compounds (3-36). The structures of the new compounds were established by spectroscopic data. The absolute configuration of 1 was validated by comparison of experimental and calculated ECD spectra. All isolated compounds were evaluated for cytotoxicity and ferroptosis inhibitory activities. Compounds 14 and 15 exerted potent cytotoxicity against CCRF-CEM cells, with IC50 values of 5.5 and 3.5 µM, respectively, whereas 26, 28, 33, and 34 significantly inhibited RSL3-induced ferroptosis, with EC50 values of 11.6, 7.2, 11.8, and 2.2 µM, respectively.


Assuntos
Ferroptose , Penicillium , Penicillium/química , Linhagem Celular Tumoral , Análise Espectral , Estrutura Molecular
12.
iScience ; 26(2): 106080, 2023 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-36824285

RESUMO

KRAS inhibitor AMG510 covalently modifies the G12C residue and inactivates the KRAS/G12C function. Because there are many reactive cysteines in the proteome, it is important to characterize AMG510 on-target modification and off-targets. Here, we presented a streamlined workflow to measure abundant AMG510 modified peptides including that of KRAS/G12C by direct profiling, and a pan-AMG510 antibody peptide IP workflow to profile less abundant AMG510 off-targets. We identified over 300 off-target sites with three distinct kinetic patterns, expanding the AMG510 modified proteome involved in the nucleocytoplasmic transport, response to oxidative stress, adaptive immune system, and glycolysis. We found that AMG510 covalently modified cys339 of ALDOA and inhibited its enzyme activity. Moreover, AMG510 modified KEAP1 cys288 and induced NRF2 accumulation in the nuclear of NSCLC cells independent of KRAS/G12C mutation. Our study provides a comprehensive resource of protein off-targets of AMG510 and elucidates potential toxicological sideeffects for this covalent KRASG12C inhibitor.

13.
Mar Drugs ; 20(12)2022 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-36547883

RESUMO

Six new citreoviridins (citreoviridins J-O, 1-6) and twenty-two known compounds (7-28) were isolated from the deep-sea-derived Penicillium citreonigrum MCCC 3A00169. The structures of the new compounds were determined by spectroscopic methods, including the HRESIMS, NMR, ECD calculations, and dimolybdenum tetraacetate-induced CD (ICD) experiments. Citreoviridins J-O (1-6) are diastereomers of 6,7-epoxycitreoviridin with different chiral centers at C-2-C-7. Pyrenocine A (7), terrein (14), and citreoviridin (20) significantly induced apoptosis for HeLa cells with IC50 values of 5.4 µM, 11.3 µM, and 0.7 µM, respectively. To be specific, pyrenocine A could induce S phase arrest, while terrein and citreoviridin could obviously induce G0-G1 phase arrest. Citreoviridin could inhibit mTOR activity in HeLa cells.


Assuntos
Penicillium , Humanos , Células HeLa , Linhagem Celular Tumoral , Penicillium/química , Espectroscopia de Ressonância Magnética/métodos , Estrutura Molecular
14.
Front Oncol ; 12: 1037934, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36353540

RESUMO

Background: The CAR T-cell therapy is a promising approach to treating hematologic malignancies. However, the application in solid tumors still has many tough challenges, including heterogenicity in antigen expressions and immunosuppressive tumor microenvironment (TME). As a new cancer treatment modality, oncolytic virotherapy can be engineered to circumvent these obstacles for CAR T cell therapy in solid tumors. Methods: In this study, an oHSV T7011 is engineered to drive ectopic expression of dual-antigens, extracellular domains of CD19 and BCMA, on the solid tumor cell surface to be targeted by approved CAR T cells. In addition, multiple immunomodulators, CCL5, IL-12, and anti-PD-1 antibody are also included to modulate the TME. The antitumor activities of T7011 in combination with CD19 or BCMA CAR T-cell were evaluated in vitro and in vivo. Results: The expression of CD19 or BMCA on the tumor cell surface could be detected after T7011 infection. The level of CCL5 in TME was also increased. Efficacy studies demonstrated that combination with T7011 and CAR-TCD19 or CAR-TBCMA cells showed significant synergistic anti-tumor responses in several solid tumor models. Conclusion: These studies indicated that the new generation of oHSV T7011 can be a promising combinational therapy with CD19 or BCMA-specific CAR T cells for the treatment of a broad range of solid tumors.

15.
Cytokine ; 160: 156055, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36194971

RESUMO

Nucleotide binding and oligomerization domain (NOD)-like receptor (NLR) initially appeared in the public view as a cytoplasmic pathogen recognition receptor (PRR) that plays an important role in innate immunity. NLRX1 is currently the only NLR known to be located in mitochondria through a mechanism presumed to be associated with its special N-terminal domain, and it establishes a novel connection between mitochondrial function and disease pathophysiology. NLRX1 functions as a negative regulator of the body's inflammatory response. Concurrently, the role of NLRX1 in regulating mitochondrial autophagy and metabolism has also been confirmed. Based on accumulating evidence, NLRX1 is involved in the occurrence and development of various diseases, including autoimmune diseases and inflammatory diseases. Research on the roles of NLRX1 in cancer, nervous system diseases and metabolic diseases has also undergone qualitative advances. However, according to current research, the function of NLRX1 is controversial, and the opposite effect has even been observed. This new study suggests that this phenomenon may be related to the specific localization of NLRX1 in cells. To date, the biological function of NLRX1 has not been comprehensively explored, but studies have introduced some new directions. For example, some recent studies have shown that NLRX1 affects pyroptosis. In this review, we summarize existing research results on NLRX1, facilitating explorations of the potential mechanism of NLRX1 and the development of new treatment strategies.


Assuntos
Imunidade Inata , Proteínas Mitocondriais , Autofagia , Humanos , Mitocôndrias/metabolismo , Proteínas Mitocondriais/metabolismo , Nucleotídeos/metabolismo
16.
J Immunol Res ; 2022: 4446805, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35692498

RESUMO

The strong tumorigenic capacity and treatment resistance made hepatocellular carcinoma (HCC) a huge threat to public health. ZNF165, the kruppel family of zinc-finger-containing transcription factors, is expressed in HCC; however, its specific role in HCC and the molecular mechanism are yet to be elucidated. In this study, we observed that ZNF165 was overexpressed in liver cancer tissues and the immune microenvironment; higher ZNF165 expression was correlated with lower overall survival in liver cancer patients. The ZNF165 knockdown in Bel7402 cells revealed the impairment of the tryptophan/kynurenine/AhR/CYP1A1 axis. Moreover, the knockdown of CYP1A1 significantly inhibited the proliferation and migration of HCC cells, and ZNF165 promoted the transcriptional activity of AhR by facilitating the nuclear translocation of CYP1A1. In conclusion, the present study argued that ZNF165 was highly expressed in liver tissues and the immune microenvironment. ZNF165 promoted the proliferation and migration of HCC cells by activating the tryptophan/kynurenine/AhR/CYP1A1 axis and promoting the expression of CYP1A1.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Linhagem Celular Tumoral , Proliferação de Células , Citocromo P-450 CYP1A1/genética , Citocromo P-450 CYP1A1/metabolismo , Proteínas de Ligação a DNA/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Cinurenina/metabolismo , Neoplasias Hepáticas/patologia , Triptofano/metabolismo , Microambiente Tumoral
17.
Toxicol Appl Pharmacol ; 436: 115854, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34974051

RESUMO

BACKGROUND: Colorectal cancer (CRC) is one of the most malignant cancers worldwide. Nonylphenol (NP) is an endocrine-disruptor chemical and plays an important role in the development of cancers. However, the effects of NP on CRC remain unclear. In this study, we aimed to investigate the potential mechanisms of NP in the pathogenesis of CRC. METHODS: The levels of AhR, TL1A and HDAC2 in CRC tissues and endothelial cells were assessed by RT-qPCR or western blot. CHIP and dual luciferase reporter assays were used to confirm the interaction between AhR and HDAC2, or HNF4α and TL1A. The CCK8, would healing and tube formation assays were conducted to evaluate the proliferation, migration and angiogenesis of HUVECs. Western blot determined HNF4α protein and HNF4α acetylation levels. The secreted TL1A protein was detected by ELISA. The angiogenesis-related factor CD31 was tested by IHC. RESULTS: The expression level of AhR was significantly up-regulated in CRC tissues and endothelial cells. Moreover, NP activated the AhR pathway mediated colorectal endothelial cell angiogenesis and proliferation, while TL1A overexpression resisted these effects caused by NP. Besides, NP was found to modulate HNF4α deacetylation through AhR/HDAC2 to inhibit TL1A. Furthermore, in vivo experiments proved that NP regulated CRC growth and angiogenesis via AhR/HDAC2/HNF4α/TL1A axis. CONCLUSION: This study revealed that NP promoted CRC growth and angiogenesis through AhR/HDAC2/HNF4α/TL1A pathway and could be a new therapeutic target for CRC treatment.


Assuntos
Neoplasias Colorretais/induzido quimicamente , Fator 4 Nuclear de Hepatócito/metabolismo , Histona Desacetilase 2/metabolismo , Neovascularização Patológica/induzido quimicamente , Fenóis/efeitos adversos , Receptores de Hidrocarboneto Arílico/metabolismo , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Células Cultivadas , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/genética , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neovascularização Patológica/genética , Neovascularização Patológica/patologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética
18.
World Neurosurg ; 158: e1-e9, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34637939

RESUMO

BACKGROUND: Making surgery as less aggressive as possible is best for elderly patients with osteoporotic vertebral compression fractures (OVCFs). Recently, we attempted a more precise, minimally invasive, and robot-assisted kyphoplasty in our clinical setting. OBJECTIVE: We sought to compare the clinical and radiologic outcomes of robot-assisted percutaneous kyphoplasty (rPKP) with those of fluoroscopy-assisted percutaneous kyphoplasty (fPKP) in treating OVCFs. METHODS: We retrospectively reviewed the clinical and radiologic data of patients with single-segment OVCF who received either rPKP or fPKP between January 2020 and December 2020 at our institution. The operation time, injected volume of cement, length of hospital stays, visual analog scale for back pain, Oswestry Disability Index, local kyphosis angle (LKA), height of fractured vertebra (HFV), and perioperative complications were compared between the 2 groups. RESULTS: A total of 212 cases were included in this study, among whom 81 cases received rPKP and 131 cases received fPKP. Both techniques exhibited satisfying improvement in pain relief and radiologic outcomes. Specifically, the rPKP costed less operation time and achieved better correction and maintenance regarding LKA, HFV, and instant pain relief (P < 0.05). The length of hospital stays, incidence of cement leakage, visual analog scale for back pain, and Oswestry Disability Index at final follow-up were comparable between 2 groups. CONCLUSIONS: rPKP provides a precise puncture and exhibits superiority in the correction and maintenance of LKA and HFV when compared with traditional fPKP. The cost-effectiveness and specific application scenarios of this technique shall be confirmed via further extensive studies.


Assuntos
Fraturas por Compressão , Cifoplastia , Cifose , Fraturas por Osteoporose , Robótica , Fraturas da Coluna Vertebral , Idoso , Dor nas Costas/tratamento farmacológico , Cimentos Ósseos/uso terapêutico , Fluoroscopia , Fraturas por Compressão/diagnóstico por imagem , Fraturas por Compressão/cirurgia , Humanos , Cifoplastia/métodos , Cifose/cirurgia , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/cirurgia , Estudos Retrospectivos , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fraturas da Coluna Vertebral/tratamento farmacológico , Fraturas da Coluna Vertebral/cirurgia , Resultado do Tratamento
19.
Clin Hemorheol Microcirc ; 80(4): 447-461, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-34864652

RESUMO

BACKGROUND: Recurrence or metastasis after surgery had been reported in hepatic epithelioid angiomylipoma (epi-AML). Most hepatic epi-AMLs were misdiagnosed with hepatocellular carcinoma or other hepatic tumors before surgery. OBJECTIVE: To describe the baseline and contrast-enhanced ultrasound (CEUS) features of hepatic epi-AMLs and to explore the potential ultrasonic features for prognosis. METHODS: The retrospective study enrolled 67 patients (56 females, 11 males) with 67 pathologically confirmed hepatic epi-AML lesions. All the lesions were examined by baseline ultrasound and 42 lesions were examined using CEUS with SonoVue (Bracco, Milan, Italy) before surgery. RESULTS: Baseline ultrasound features of hepatic epi-AMLs included heterogeneous echo (86.6%), well-defined border (68.7%), hypoecho (64.2%), regular morphology (62.7%), peripheral-tumor arc-shaped or ring-like vessels (53.7%), and low value of resistive index (0.51±0.08). CEUS features of hepatic epi-AMLs included arterial phase hyper-enhancement with smooth and well-defined margin (100%), peripheral-tumor ring-like vessels (57.1%), and intra-tumor vessels (52.4%). Some CEUS features, including arterial phase heterogeneously tortuous filling, intra-tumor vessels and peripheral-tumor ring-like vessels were more commonly found in hepatic epi-AMLs of uncertain malignant potential/malignant than in benign hepatic epi-AMLs (p < 0.05). CONCLUSIONS: Baseline ultrasound and CEUS features may be useful in diagnosis of hepatic epi-AML, and some CEUS features may be indicative of its malignant potential.


Assuntos
Angiomiolipoma , Carcinoma Hepatocelular , Neoplasias Hepáticas , Angiomiolipoma/diagnóstico por imagem , Angiomiolipoma/patologia , Meios de Contraste , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/patologia , Masculino , Estudos Retrospectivos , Ultrassonografia
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