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1.
Chaos ; 33(1): 013133, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36725640

RESUMO

A kind of top with a fractional operator is discussed in this paper. The top has a periodic nonlinear pulse kick sequence in the magnetic field and constant precessing around the magnetic field. Then, a fractional quantum kicked top map based on the Caputo derivative is proposed. The numerical solutions of the fractional difference equation are obtained, and the chaotic behavior is observed numerically in three aspects. Fractional quantum dynamics behaviors take place in a finite dimensional Hilbert space where the squared angular momentum is free precession. Finally, the dynamic behaviors of the fractional quantum kicked top map are systematically analyzed by using the bifurcation diagram, the phase diagram, and the maximum Lyapunov exponent.

2.
J Nat Prod ; 85(8): 2100-2103, 2022 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-35968659

RESUMO

To study the chemical constituents from the ripe fresh fruits of Syzygium samarangense (wax apple) and their potential health effects, a phytochemical investigation was undertaken. A new δ-lactone derivative, syzysamalactone (1), along with a known biogenetically related δ-lactone derivative, 6-pentyl-α-pyrone (2), were isolated from the fresh ripe fruits of S. samarangense. Syzysamalactone (1) is an unusual 11-carbon δ-lactone derivative, and its chemical structure and absolute configuration were elucidated by spectroscopic data analysis. A plausible biogenetic pathway for 1 was also proposed. Furthermore, the potential neuroprotective effects of compounds 1 and 2 were assessed. As a result, compounds 1 and 2 displayed notable neuroprotective effects with EC50 values of 0.29 ± 0.03 and 1.28 ± 0.06 µM, respectively, using the SH-SY5Y human neuroblastoma cell line. This is the first report of δ-lactone derivatives showing significant neuroprotective activities.


Assuntos
Neuroblastoma , Fármacos Neuroprotetores , Syzygium , Carbono/metabolismo , Frutas/química , Humanos , Lactonas/metabolismo , Lactonas/farmacologia , Estrutura Molecular , Neuroblastoma/tratamento farmacológico , Fármacos Neuroprotetores/metabolismo , Fármacos Neuroprotetores/farmacologia , Syzygium/química
3.
Bioorg Chem ; 129: 106177, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36183563

RESUMO

Two new trimethoxyl A2B triaryl corroles 10-(2,4,6-trimethoxyphenyl)-5,15-bis(pentafluorophenyl)- corrole (1) and 10-(3,4,5-trimethoxyphenyl)-5,15-bis(pentafluorophenyl)-corrole (2) and their gallium(III) and phosphorus(V) (1-Ga, 1-P, 2-Ga and 2-P) complexes had been prepared and well characterized by UV-vis, NMR and HR-MS. Among all compounds, 2-Ga, 1-P and 2-P showed excellent in vivo photodynamic activity against the MDA-MB-231, A549, Hela and HepG2 cell lines upon light irradiation at 625 nm. And 2-P even exhibited higher phototoxicity than the clinical photosensitizer temoporfin. Also, 2-P exhibited the highest singlet oxygen quantum yield and photostability. The preliminary investigation revealed that 2-P could be rapidly absorbed by tumor cells and mainly located in the cytoplasm. After photodynamic therapy (PDT) treatment with 2-P, mitochondrial membrane potential destruction, intracellular ROS level increasing and nuclear fragmentation of cancer cells could be observed. Cell cycle analysis demonstrated that the 2-P PDT may cause tumor cell arrest at sub-G1 stage and induce early and late apoptosis of cells. These results suggest that 2-P is a promising candidate as a photosensitizer for photodynamic therapy.


Assuntos
Gálio , Fotoquimioterapia , Humanos , Gálio/farmacologia , Gálio/química , Fármacos Fotossensibilizantes/farmacologia , Fósforo/farmacologia , Linhagem Celular Tumoral
4.
J Org Chem ; 86(24): 17722-17726, 2021 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-34817178

RESUMO

A unique prenylated bicarbazole alkaloid, clausanisumine (1), and two biogenetically related known monomer carbazole alkaloids, mukonal (2) and 3-methylcarbazole (3), were isolated from the fruits of Clausena anisum-olens. Clausanisumine (1) was an uncommon prenylated bicarbazole alkaloid, possessing an unprecedented carbon skeleton, which was composed of a simple carbazole alkaloid and a prenylated carbazole alkaloid. The chemical structure of 1 was established by a combination of comprehensive spectral methods. A plausible biosynthetic pathway of 1 was also proposed. Additionally, the potential anti-HIV activities of all isolates 1-3 in vitro were evaluated. Compound 1 exhibited remarkable anti-HIV-1 reverse transcriptase effects showing an EC50 value of 18.58 nM. The discovery of the prenylated bicarbazole alkaloid from C. anisum-olens with notable anti-HIV activity would be meaningful to discovering and developing new anti-HIV drugs.


Assuntos
Alcaloides , Fármacos Anti-HIV , Clausena , Alcaloides/farmacologia , Fármacos Anti-HIV/farmacologia , Carbazóis/farmacologia , Frutas , Estrutura Molecular
5.
Inorg Chem ; 60(4): 2234-2245, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33480681

RESUMO

A series of halogenated gallium corroles were synthesized and characterized by UV-vis, HRMS, NMR, and FT-IR. The interaction between these gallium corroles and calf thymus DNA had been investigated by spectroscopic methods. These gallium corroles would interact with CT-DNA via an outside binding mode. The photodynamic antitumor activity in vitro of these gallium corroles toward different cell lines had also been tested. 3-Ga displayed low cytotoxicity to normal cells under both light and dark conditions but high phototoxicity to liver cancer cells HepG2. The vitro experiment results showed that 3-Ga could be efficiently absorbed by tumor cells. After light illumination, it may induce reactive oxygen species (ROS) and cause destruction of the mitochondrial membrane potential, which may finally trigger tumor cell apoptosis. Flow cytometry results showed that HepG2 cells were mainly distributed in the sub-G0 phase, which corresponds to cells with highly fragmented DNA or dead cells generally. This suggests that 3-Ga could lead to tumor cell apoptosis after light illumination.


Assuntos
DNA/química , Gálio/química , Halogenação , Neoplasias/tratamento farmacológico , Fotoquimioterapia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/farmacologia , Porfirinas/química , Animais , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Células Hep G2 , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos BALB C , Neoplasias/metabolismo , Fármacos Fotossensibilizantes/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Análise Espectral/métodos , Testes de Toxicidade Aguda
6.
J Nat Prod ; 84(12): 3117-3121, 2021 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-34812640

RESUMO

Two unusual phenanthrene derivatives related to aporphine alkaloids, artapilosines A (1) and B (2), as well as two biogenetically related known aporphine alkaloids, (-)-anonaine (3) and (-)-N-acetylanonaine (4), were separated and purified from Artabotrys pilosus. Artapilosine A (1) is the first compound representative of a new class of phenanthrene derivatives having an unprecedented carbon skeleton, in which the six-membered nitrogen-containing heterocyclic structure in a typical aporphine alkaloid was substituted with a unique five-membered carbocyclic ring. This is the first report of the formation of a carbon-carbon bond between C-5 and C-6a in 1 with the loss of the nitrogen atom N-6 in the classic aporphine alkaloid. Artapilosine B (2) is a novel phenanthrene derivative having a hydroxyethyl as a substituent on the phenanthrene ring. Their chemical structures as well as absolute configurations were determined based on analysis of spectroscopic data. Additionally, the potential anti-HIV activities of all isolates 1-4 were appraised. Artapilosines A (1) and B (2) showed notable anti-HIV reverse transcriptase affects, with EC50 values of 20.93 and 125.29 nM, respectively. These results suggested that the discovery of these novel phenanthrene derivatives from A. pilosus with remarkable anti-HIV effects could be essentially important for the researching and developing of new anti-HIV agents.


Assuntos
Annonaceae/química , Aporfinas/isolamento & purificação , Fenantrenos/química , Fármacos Anti-HIV/química , Fármacos Anti-HIV/isolamento & purificação , Fármacos Anti-HIV/farmacologia , Aporfinas/química , Humanos , Estrutura Molecular
7.
Bioorg Chem ; 90: 103085, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31279233

RESUMO

A series of iron(III), manganese(III) and copper(III) mono-hydroxyl corrole complexes had been prepared and well characterized by UV-vis, 1H NMR, 19F NMR and HR-MS. These metallocorroles may bind to CT-DNA through external binding mode. Metallocorrole Fe-2c exhibited significant phototoxicity and low toxicity toward A549 tumor cells. While manganese (III) and copper (III) corroles showed hypotoxicity to A549, MCF-7 and HepG-2 tumor cells, whether under dark or illumination conditions. All tested metallocorroles exhibited non-toxicity to human normal cells (GES-1) with or without irradiation at 625 nm. Cell cycle analysis indicated that metallocorrole Fe-2c arrested the cell cycle at G2/M phase and increased the Sub-G1 phase in A549 cell lines. It was mainly localized at mitochondria and could significantly reduce mitochondrial membrane potential after photodynamic treatment, which would further induce tumor cell apoptosis.


Assuntos
Antineoplásicos/farmacologia , Cobre/química , DNA/metabolismo , Compostos Férricos/química , Manganês/química , Neoplasias/terapia , Porfirinas/química , Antineoplásicos/química , Apoptose , Humanos , Radical Hidroxila , Potencial da Membrana Mitocondrial , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neoplasias/patologia , Fotoquimioterapia , Células Tumorais Cultivadas
8.
Molecules ; 22(11)2017 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-29120395

RESUMO

A one-pot synthesis of bulky bis-pocket A3B-type meso-cyano porphyrin, 5-cyano-10,15,20-tris(2,4,6-triphenylphenyl)porphyrin, has been accomplished via trifluoroacetic acid (TFA) catalyzed condensation of pyrrole and 2,4,6-triphenylbenzaldehyde in an acceptable yield of about 4%. DDQ served as oxidant and the cyanating agent.


Assuntos
Porfirinas/síntese química , Estrutura Molecular , Porfirinas/química , Espectroscopia de Prótons por Ressonância Magnética , Análise Espectral
9.
Cell Tissue Res ; 360(2): 195-207, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25549759

RESUMO

Tendon injuries are commonly encountered in the clinic, disrupting the patient's normal work/life routine and damaging the career life of athletes. Currently, there is still no effective treatment for tendon injury. Tendon tissue engineering appears to be a promising route for tendon repair and regeneration. However, current strategies utilized in research are still far away from clinical applications due to unsuccessful cellular differentiation to tendon/tenocytes. In this review, we focus on the current physical strategies (mechanical stimulation and extracellular matrix topography) and evaluate their roles in precise and stepwise tendon differentiation. A systematic comprehension of normal tendon development process by structure, gene profile and physical microenvironment analysis is likely suggestive for stepwise tenocyte differentiation.


Assuntos
Diferenciação Celular , Células-Tronco/metabolismo , Traumatismos dos Tendões/terapia , Tendões/metabolismo , Engenharia Tecidual/métodos , Animais , Humanos , Células-Tronco/patologia , Traumatismos dos Tendões/metabolismo , Traumatismos dos Tendões/patologia , Tendões/patologia
10.
J Med Chem ; 67(11): 9054-9068, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38781403

RESUMO

Molecular hybridization is a well-established strategy for developing new drugs. In the pursuit of promising photosensitizers (PSs) with enhanced photodynamic therapy (PDT) efficiency, a series of novel 5-fluorouracil (5FU) gallium corrole conjugates (1-Ga-4-Ga) were designed and synthesized by hybridizing a chemotherapeutic drug and PSs. Their photodynamic antitumor activity was also evaluated. The most active complex (2-Ga) possesses a low IC50 value of 0.185 µM and a phototoxic index of 541 against HepG2 cells. Additionally, the 5FU-gallium corrole conjugate (2-Ga) exhibited a synergistic increase in cytotoxicity under irradiation. Excitedly, treatment of HepG2 tumor-bearing mice with 2-Ga under irradiation could completely ablate tumors without harming normal tissues. 2-Ga-mediated PDT could disrupt mitochondrial function, cause cell cycle arrest in the sub-G1 phase, and activate the cell apoptosis pathway by upregulating the cleaved PARP expression and the Bax/Bcl-2 ratios. This work provides a useful strategy for the design of new corrole-based chemo-photodynamic therapy drugs.


Assuntos
Apoptose , Fluoruracila , Gálio , Fotoquimioterapia , Fármacos Fotossensibilizantes , Porfirinas , Fluoruracila/farmacologia , Fluoruracila/química , Fluoruracila/uso terapêutico , Humanos , Gálio/química , Gálio/farmacologia , Animais , Porfirinas/farmacologia , Porfirinas/química , Porfirinas/uso terapêutico , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/química , Fármacos Fotossensibilizantes/síntese química , Fármacos Fotossensibilizantes/uso terapêutico , Camundongos , Apoptose/efeitos dos fármacos , Células Hep G2 , Antineoplásicos/farmacologia , Antineoplásicos/química , Antineoplásicos/síntese química , Camundongos Endogâmicos BALB C , Camundongos Nus
11.
Cancer Lett ; 598: 217094, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38945204

RESUMO

Recent therapeutic strategies for the treatment of triple-negative breast cancer (TNBC) have shifted the focus from vascular growth factors to endothelial cell metabolism. This study highlights the underexplored therapeutic potential of peri-tumoral electroacupuncture, a globally accepted non-pharmacological intervention for TNBC, and molecular mechanisms. Our study showed that peri-tumoral electroacupuncture effectively reduced the density of microvasculature and enhanced vascular functionality in 4T1 breast cancer xenografts, with optimal effects on day 3 post-acupuncture. The timely integration of peri-tumoral electroacupuncture amplified the anti-tumor efficacy of paclitaxel. Multi-omics analysis revealed Glyoxalase 1 (Glo1) and the associated methylglyoxal-glycolytic pathway as key mediators of electroacupuncture-induced vascular normalization. Peri-tumoral electroacupuncture notably reduced Glo1 expression in the endothelial cells of 4T1 xenografts. Using an in vivo matrigel plug angiogenesis assay, we demonstrated that either Glo1 knockdown or electroacupuncture inhibited angiogenesis. In contrast, Glo1 overexpression increased blood vessel formation. In vitro pharmacological inhibition and genetic knockdown of Glo1 in human umbilical vein endothelial cells inhibited proliferation and promoted apoptosis via downregulating the methylglyoxal-glycolytic pathway. The study using the Glo1-silenced zebrafish model further supported the role of Glo1 in vascular development. This study underscores the pivotal role of Glo1 in peri-tumoral electroacupuncture, spotlighting a promising avenue for enhancing vascular normalization and improving TNBC treatment outcomes.

12.
Exp Mol Med ; 56(1): 177-191, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38177295

RESUMO

Dysregulation of wild-type p53 turnover is a key cause of hepatocellular carcinoma (HCC), yet its mechanism remains poorly understood. Here, we report that WD repeat and SOCS box containing protein 2 (WSB2), an E3 ubiquitin ligase, is an independent adverse prognostic factor in HCC patients. WSB2 drives HCC tumorigenesis and lung metastasis in vitro and in vivo. Mechanistically, WSB2 is a new p53 destabilizer that promotes K48-linked p53 polyubiquitination at the Lys291 and Lys292 sites in HCC cells, leading to p53 proteasomal degradation. Degradation of p53 causes IGFBP3-dependent AKT/mTOR signaling activation. Furthermore, WSB2 was found to bind to the p53 tetramerization domain via its SOCS box domain. Targeting mTOR with everolimus, an oral drug, significantly blocked WSB2-triggered HCC tumorigenesis and metastasis in vivo. In clinical samples, high expression of WSB2 was associated with low wild-type p53 expression and high p-mTOR expression. These findings demonstrate that WSB2 is overexpressed and degrades wild-type p53 and then activates the IGFBP3-AKT/mTOR axis, leading to HCC tumorigenesis and lung metastasis, which indicates that targeting mTOR could be a new therapeutic strategy for HCC patients with high WSB2 expression and wild-type p53.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Neoplasias Pulmonares , Humanos , Carcinogênese , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/genética , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina/uso terapêutico , Neoplasias Hepáticas/metabolismo , Neoplasias Pulmonares/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteína Supressora de Tumor p53/genética
13.
J Mol Cell Biol ; 15(2)2023 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-36822623

RESUMO

Helicase-like transcription factor (HLTF) has been found to be involved in the maintenance of genome stability and tumour suppression, but whether its downregulation in cancers is associated with posttranslational regulation remains unclear. Here, we observed that HLTF was significantly downregulated in hepatocellular carcinoma (HCC) tissues and positively associated with the survival of HCC patients. Mechanistically, the decreased expression of HLTF in HCC was attributed to elevated ß-TrCP-mediated ubiquitination and degradation. Knockdown of HLTF enhanced p62 transcriptional activity and mammalian target of rapamycin (mTOR) activation, leading to HCC tumourigenesis. Inhibition of mTOR effectively blocked ß-TrCP overexpression- or HLTF knockdown-mediated HCC tumourigenesis and metastasis. Furthermore, in clinical tissues, decreased HLTF expression was positively correlated with elevated expression of ß-TrCP, p62, or p-mTOR in HCC patients. Overall, our data not only uncover new roles of HLTF in HCC cell proliferation and metastasis, but also reveal a novel posttranslational modification of HLTF by ß-TrCP, indicating that the ß-TrCP/HLTF/p62/mTOR axis may be a new oncogenic driver involved in HCC development. This finding provides a potential therapeutic strategy for HCC patients by targeting the ß-TrCP/HLTF/p62/mTOR axis.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/metabolismo , Proteínas Contendo Repetições de beta-Transducina/genética , Proteínas Contendo Repetições de beta-Transducina/metabolismo , Linhagem Celular Tumoral , Neoplasias Hepáticas/patologia , Sirolimo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Carcinogênese/genética , Serina-Treonina Quinases TOR/metabolismo , Proteínas de Ligação a DNA/metabolismo
14.
Cell Rep ; 42(7): 112812, 2023 07 25.
Artigo em Inglês | MEDLINE | ID: mdl-37450367

RESUMO

Hepatocellular carcinoma (HCC), the most common liver cancer, occurs mainly in men, but the underlying mechanism remains to be further explored. Here, we report that ubiquitinated glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is responsible for HCC tumorigenesis in males. Mechanistically, FBXW10 promotes GAPDH polyubiquitination and activation; VRK2-dependent phosphorylation of GAPDH Ser151 residue is critical for GAPDH ubiquitination and activation. Activated GAPDH interacts with TRAF2, leading to upregulation of the canonical and noncanonical NF-κB pathways, and increases PD-L1 and AR-VRK2 expression, followed by induction of immune evasion, HCC tumorigenesis, and metastasis. Notably, the GAPDH inhibitor koningic acid (KA) activates immune response and protects against FBXW10-driven HCC in vivo. In HCC clinical samples, the expression of active GAPDH is positively correlated with that of FBXW10 and VRK2. We propose that the FBXW10/AR/VRK2/GAPDH/NF-κB axis is critical for HCC tumorigenesis in males. Targeting this axis with KA is a potential therapeutic strategy for male HCC patients.


Assuntos
Carcinoma Hepatocelular , Proteínas F-Box , Neoplasias Hepáticas , Animais , Masculino , Camundongos , Carcinogênese/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Transformação Celular Neoplásica , Gliceraldeído-3-Fosfato Desidrogenases/metabolismo , Neoplasias Hepáticas/metabolismo , Camundongos Transgênicos , NF-kappa B/metabolismo , Fosforilação , Ubiquitinação , Proteínas F-Box/metabolismo
15.
Nat Prod Res ; 37(9): 1456-1462, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-34894893

RESUMO

The phytochemical investigation on the fruits of Morinda citrifolia led to the isolation and characterization of a new anthraquinone, moricitrifone (1), along with seven known anthraquinones (2-8). The chemical structure of 1 was elucidated by extensive spectral analyses. The known compounds (2-8) were identified by comparing their spectral data with those reported in the literature. The antiproliferative activities of all isolated anthraquinones (1-8) against five human cancer cell lines: HL-60, SMMC-7721, A-549, MCF-7 and SW480 were evaluated in vitro. Compounds 1-8 exhibited remarkable antiproliferative activities with IC50 values ranging from 0.26 ± 0.05 to 16.58 ± 0.18 µM, which were comparable to those of doxorubicin.


Assuntos
Morinda , Humanos , Morinda/química , Estrutura Molecular , Frutas/química , Extratos Vegetais/química , Antraquinonas/química
16.
Chemosphere ; 312(Pt 1): 137253, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36395896

RESUMO

Photocatalytic disinfection is considered a promising method for eliminating the hazards of pathogenic bacteria. Graphitic carbon nitride (g-C3N4) is an ideal photocatalytic bacterial inactivation material for its advantage of tunable band structure, good stability and easy preparation. This work has constructed a novel defective 3D porous g-C3N4 by cyanamide carbonation using dendritic mesoporous silica template. The direct loading of Fe3O4 nanoparticles provided an excellent pg-C3N4-Fe3O4 photocatalyst suitable for water disinfection. Compared to pristine g-C3N4, the prepared 3D porous defective g-C3N4-Fe3O4 exhibited the enhanced visible light absorbance as indicated by the band gap decreasing of 0.66 eV, and about 3 and 10 fold increase of photo-induced current response and O2 adsorption respectively. The pg-C3N4-Fe3O4 showed excellent visible-light-driven photocatalytic bactericidal activity. It could kill 1 × 107 cfu mL-1Escherichia coli completely within 1 h under visible-light illumination (100 mW cm-2) with good reusability, its logarithmic bacterial inactivation efficiency was about 2.5 fold higher than pg-C3N4. The enhanced bactericidal performance is mainly ascribed to the Fe3O4 involved cascade photo-Fenton reaction.


Assuntos
Desinfecção , Luz , Porosidade , Catálise , Desinfecção/métodos , Bactérias , Escherichia coli
17.
Cancer Lett ; 566: 216257, 2023 07 10.
Artigo em Inglês | MEDLINE | ID: mdl-37277019

RESUMO

The incidence rate of human hepatocellular carcinoma (HCC) is approximately three times higher in males than in females. A better understanding of the mechanisms underlying HCC development in males could lead to more effective therapies for HCC. Our previous study found that FBXW10 played a critical role in promoting HCC development in male mice and patients, but the mechanism remains unknown. Here, we found that FBXW10 promoted K63-linked ANXA2 polyubiquitination and activation in HCC tissues from males, and this process was required for S6K1-mediated phosphorylation. Activated ANXA2 further translocated from the cytoplasm to the cell membrane to bind KRAS and then activated the MEK/ERK pathway, leading to HCC proliferation and lung metastasis. Interfering with ANXA2 significantly blocked FBXW10-driven HCC growth and lung metastasis in vitro and in vivo. Notably, membrane ANXA2 was upregulated and positively correlated with FBXW10 expression in male HCC patients. These findings offer new insights into the regulation and function of FBXW10 signaling in HCC tumorigenesis and metastasis and suggest that the FBXW10-S6K1-ANXA2-KRAS-ERK axis may serve as a potential biomarker and therapeutic target in male HCC patients with high FBXW10 expression.


Assuntos
Anexina A2 , Carcinoma Hepatocelular , Proteínas F-Box , Neoplasias Hepáticas , Neoplasias Pulmonares , Feminino , Humanos , Masculino , Animais , Camundongos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Carcinogênese/patologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Anexina A2/genética , Anexina A2/metabolismo , Proteínas F-Box/genética , Proteínas F-Box/metabolismo
18.
Breastfeed Med ; 16(9): 759-764, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33872053

RESUMO

Background: We have already known that idiopathic granulomatous mastitis (IGM) is a rare benign chronic inflammatory disorder that can clinically mimic breast carcinoma, especially affects parous women of childbearing age, but there is little literature to report about pregnancy associated granulomatous mastitis (PAGM). The aim of our study is to report and describe the clinical signs, managements, clinical course, and clinical outcomes after treatment of PAGM in our hospital. Methods: We retrospectively analyzed 15 pregnant patients who were diagnosed as PAGM in our hospital collected from December 2018 to December 2020 by reviewing medical records and questionnaire survey, including the patients' characteristics, clinical presentations, microbiological workups, tissue pathology, treatment modalities, outcomes, and follow-up data. Results: The mean age of these patients at diagnosis was 30.5 (range 24-35) years. All patients had one birth before, and had at least two gravida times, 6 of them (40%) had three gravida times, and only one of them had four gravida times at diagnosis. The mean weeks of gestational age were 23.7 (range 4-37) weeks. Two patients' BMI were greater than 30, which were considered obese. The mean time to presentation since last delivery was 38.4 (range 19-78) months. All patients had a history of breastfeeding; the average breastfeeding time was 12.97 months. Just 2 of them were diagnosed with lactational mastitis before. One patient smoked before, 1 patient had oral contraceptive pills before, 4 patients had breast trauma recently, 5 patients had positive bacterial culture of pyogenic fluids, 3 patients had nipple retraction, 6 patients had abnormal humoral immunity, shown as elevated C3 or C4, and 2 patients had elevated serum prolactin. All patients presented as a breast mass with pain; two of them had erythema nodosum and oligoarthritis. Nearly all patients had unilateral lesion. The mean follow-up was 11 (range 1-24) months. Thirteen patients gave birth to a healthy baby, and all babies had a healthy growth and development. Almost all patients chose observation during pregnancy. Nine patients demonstrated complete remission, five of them underwent surgery after steroids and/or antibiotics, one patient had observation alone, two chose postpartum steroids alone, and the last one chose postpartum antibiotics alone. The average time to complete remission was 11.2 (range 7-18) months. Conclusions: In general, PAGM is a much rare disorder which has onset during pregnancy, and mainly happens in the second trimester and the third trimester. PAGM patients were all parous women and generally within 5 years of their last pregnancy, also with uncertain etiology and pathogenesis. Observational therapy during pregnancy for PAGM is reliable and feasible.


Assuntos
Neoplasias da Mama , Mastite Granulomatosa , Mastite , Adulto , Mama , Aleitamento Materno , Feminino , Mastite Granulomatosa/diagnóstico , Mastite Granulomatosa/terapia , Humanos , Lactente , Gravidez , Estudos Retrospectivos , Adulto Jovem
19.
Elife ; 102021 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-34779401

RESUMO

Dysregulation of tumor-relevant proteins may contribute to human hepatocellular carcinoma (HCC) tumorigenesis. FBXO45 is an E3 ubiquitin ligase that is frequently elevated expression in human HCC. However, it remains unknown whether FBXO45 is associated with hepatocarcinogenesis and how to treat HCC patients with high FBXO45 expression. Here, IHC and qPCR analysis revealed that FBXO45 protein and mRNA were highly expressed in 54.3% (57 of 105) and 52.2% (132 of 253) of the HCC tissue samples, respectively. Highly expressed FBXO45 promoted liver tumorigenesis in transgenic mice. Mechanistically, FBXO45 promoted IGF2BP1 ubiquitination at the Lys190 and Lys450 sites and subsequent activation, leading to the upregulation of PLK1 expression and the induction of cell proliferation and liver tumorigenesis in vitro and in vivo. PLK1 inhibition or IGF2BP1 knockdown significantly blocked FBXO45-driven liver tumorigenesis in FBXO45 transgenic mice, primary cells, and HCCs. Furthermore, IHC analysis on HCC tissue samples revealed a positive association between the hyperexpression of FBXO45 and PLK1/IGF2BP1, and both had positive relationship with poor survival in HCC patients. Thus, FBXO45 plays an important role in promoting liver tumorigenesis through IGF2BP1 ubiquitination and activation, and subsequent PLK1 upregulation, suggesting a new strategy for treating HCC by targeting FBXO45/IGF2BP1/PLK1 axis.


Assuntos
Carcinoma Hepatocelular/patologia , Proteínas F-Box/metabolismo , Neoplasias Hepáticas/patologia , Animais , Carcinogênese , Proteínas de Ciclo Celular/metabolismo , Proliferação de Células , Proteínas F-Box/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos Transgênicos , Pessoa de Meia-Idade , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , RNA Mensageiro , Análise de Sobrevida , Ubiquitinação , Quinase 1 Polo-Like
20.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 32(2): 136-40, 2010 Apr.
Artigo em Zh | MEDLINE | ID: mdl-20450540

RESUMO

OBJECTIVE: To observe the function of gamma delta T lymphocytes and the polymorphism of T cell receptor V delta chain in the lungs of asthmatic patients and explore the role of gamma delta T cells in airway inflammation. METHODS: Bronchoalveolar lavage fluid BALF was obtained from 7 asthmatic patients and 7 healthy control individuals. The percentage of gamma delta T cell in BALF was measured by flow cytometry. The gamma delta T cell in BALF was purified by magnetic labeled beads. Proliferous activity was examined by MTT assay. Cytokines secreted by gamma delta T cells in medium was assessed by enzyme-linked immunosorbent assay. Polymorphism of T cell receptor V delta chain was detected by RT-PCR and gene scan analysis. RESULTS: The proportion of gamma delta T cell in the BALF of asthmatic patients [(6.39+/-0.71)%] was significantly higher than that in control subjects [(2.62+/-0.37)%] (P<0.01). The proportion of macrophage in the BALF of asthmatic patients [(81+/-4)] was significantly lower than that in control subjects [(86+/-2)] (P<0.05). The proliferation rate of asthmatic patients [(284.2+/-43.6)%] was significantly higher than that of control subjects [(217.5+/-59.5)%] (P<0.05). Interleukin-4 secreted by gamma delta T cells of asthmatic patients [(18.9+/-3.1) pg/ml)] significantly increased when compared with the control subjects [(14.1+/-3.0) pg/ml] (P<0.05). The polymorphism of T cell receptor V delta chain was not significantly different between these two groups. CONCLUSIONS: The increase of gamma delta T cells in the lung of asthmatic patients further exacerbates Th1/Th2 disturbance and airway inflammation. Antigen recognition by gamma delta T cells is non-specific.


Assuntos
Asma/imunologia , Genes Codificadores da Cadeia delta de Receptores de Linfócitos T/genética , Genes Codificadores da Cadeia gama de Receptores de Linfócitos T/genética , Subpopulações de Linfócitos T/imunologia , Adulto , Asma/genética , Líquido da Lavagem Broncoalveolar/citologia , Estudos de Casos e Controles , Proliferação de Células , Citocinas/metabolismo , Feminino , Humanos , Região Variável de Imunoglobulina/genética , Pulmão/imunologia , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Subpopulações de Linfócitos T/metabolismo , Equilíbrio Th1-Th2
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