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1.
Molecules ; 26(17)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34500649

RESUMO

At present, most of the reported planar pentacoordinate clusters are similar to the isoelectronic substitution of CAl5+, with 18 counting electrons. Meanwhile, the regular planar pentacoordinate boron systems are rarely reported. Hereby, a sulphur-bridged BAl5S5+ system with a five-pointed star configuration and 17 counting electrons is identified at the global energy minimum through the particle-swarm optimization method, based on the previous recognition on bridged sulphur as the peripheral tactics to the stable planar tetracoordinate carbon and boron. Its outstanding stability has been demonstrated by thermodynamic analysis at 900 K, electronic properties and chemical bonding analysis. This study provides adequately theoretical basis and referable data for its experimental capture and testing.

2.
Nature ; 599(7884): 222-228, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34587621

RESUMO

The transition metal kagome lattice materials host frustrated, correlated and topological quantum states of matter1-9. Recently, a new family of vanadium-based kagome metals, AV3Sb5 (A = K, Rb or Cs), with topological band structures has been discovered10,11. These layered compounds are nonmagnetic and undergo charge density wave transitions before developing superconductivity at low temperatures11-19. Here we report the observation of unconventional superconductivity and a pair density wave (PDW) in CsV3Sb5 using scanning tunnelling microscope/spectroscopy and Josephson scanning tunnelling spectroscopy. We find that CsV3Sb5 exhibits a V-shaped pairing gap Δ ~ 0.5 meV and is a strong-coupling superconductor (2Δ/kBTc ~ 5) that coexists with 4a0 unidirectional and 2a0 × 2a0 charge order. Remarkably, we discover a 3Q PDW accompanied by bidirectional 4a0/3 spatial modulations of the superconducting gap, coherence peak and gap depth in the tunnelling conductance. We term this novel quantum state a roton PDW associated with an underlying vortex-antivortex lattice that can account for the observed conductance modulations. Probing the electronic states in the vortex halo in an applied magnetic field, in strong field that suppresses superconductivity and in zero field above Tc, reveals that the PDW is a primary state responsible for an emergent pseudogap and intertwined electronic order. Our findings show striking analogies and distinctions to the phenomenology of high-Tc cuprate superconductors, and provide groundwork for understanding the microscopic origin of correlated electronic states and superconductivity in vanadium-based kagome metals.

3.
Front Immunol ; 12: 616074, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33732240

RESUMO

Berberine, which is a traditional Chinese medicine can inhibit tumorigenesis by inducing tumor cell apoptosis. However, the immunoregulatory of effects berberine on T cells remains poorly understood. Here, we first examined whether berberine can prolong allograft survival by regulating the recruitment and function of T cells. Using a major histocompatibility complex complete mismatch mouse heterotopic cardiac transplantation model, we found that the administration of moderate doses (5 mg/kg) of berberine significantly prolonged heart allograft survival to 19 days and elicited no obvious berberine-related toxicity. Compared to that with normal saline treatment, berberine treatment decreased alloreactive T cells in recipient splenocytes and lymph node cells. It also inhibited the activation, proliferation, and function of alloreactive T cells. Most importantly, berberine treatment protected myocardial cells by decreasing CD4+ and CD8+ T cell infiltration and by inhibiting T cell function in allografts. In vivo and in vitro assays revealed that berberine treatment eliminated alloreactive T lymphocytes via the mitochondrial apoptosis pathway, which was validated by transcriptome sequencing. Taken together, we demonstrated that berberine prolongs allograft survival by inducing apoptosis of alloreactive T cells. Thus, our study provides more evidence supporting the potential use of berberine in translational medicine.


Assuntos
Apoptose/efeitos dos fármacos , Berberina/farmacologia , Sobrevivência de Enxerto/efeitos dos fármacos , Transplante de Coração , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Linfócitos T/efeitos dos fármacos , Linfócitos T/fisiologia , Animais , Apoptose/imunologia , Berberina/uso terapêutico , Biomarcadores , Citocinas/metabolismo , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/metabolismo , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto/imunologia , Transplante de Coração/efeitos adversos , Transplante de Coração/métodos , Mediadores da Inflamação/metabolismo , Ativação Linfocitária/imunologia , Masculino , Camundongos , Transplante Homólogo
5.
J Cancer ; 11(10): 3061-3071, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32226521

RESUMO

Background: Clear cell renal cell carcinoma (ccRCC) is characterized by high metastatic potential, and the epithelial-mesenchymal transition (EMT) has been shown to play a key role in multiple cancer progression, migration and metastasis and is the leading cause of poor prognosis. Currently, tumor necrosis factor-α-induced protein 8 (TNFAIP8/TIPE) is a newly discovered tumorigenesis factor, and TNFAIP8 and the EMT influence the migration of renal cancer cells. Methods: In this study, we first analyzed the relationship between TNFAIP8 and ccRCC using bioinformatics, followed by immunohistochemistry to evaluate the relationship between the two in clinical samples. Subsequently, reverse transcription PCR and western blotting confirmed the expression of TNFAIP8 in ccRCC cells. Furthermore, we measured the migration and invasion abilities by using wound healing and transwell assays after overexpression or knockdown of TNFAIP8 in cells. In addition, we verified whether TNFAIP8 affects the EMT process in ccRCC by quantitative real-time PCR, western blotting, immunohistochemistry and immunofluorescence experiments. Results: Through database analysis, we found that TNFAIP8 was highly expressed in ccRCC patients and was positively correlated with tumor stage and grade, indicating that TNFAIP8 is associated with the development of advanced ccRCC and poor prognosis. We subsequently confirmed that TNFAIP8 was abnormally overexpressed in clinical samples and ccRCC cell lines and that TNFAIP8 promoted ccRCC cell migration and invasion in vitro. Finally, we found that TNFAIP8 regulated EMT-related molecule expression and regulated the EMT process. Conclusion: High expression of TNFAIP8 reinforces migration and regulates the EMT in ccRCC, conferring the metastatic potential of ccRCC and suggesting that TNFAIP8 may be a potential therapeutic target for the treatment of advanced ccRCC.

6.
Int J Biol Sci ; 16(2): 272-283, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31929755

RESUMO

Background: Metastasis is the leading cause of death in colorectal cancer (CRC) patients. It is regulated mainly by tumor cell angiogenesis, and angiogenesis is caused by the binding of vascular endothelial growth factor (VEGF) to vascular endothelial growth factor receptor 2 (VEGFR2). Tumor necrosis factor-α-induced protein 8 (TNFAIP8, hereto after TIPE) plays an important role in tumorigenesis, development, and prognosis. However, the relationship between TIPE and VEGFR2 in CRC angiogenesis and the mechanism of action remain unknown. Method: In this study, we used quantitative real-time PCR, Western blotting and immunohistochemistry to detect TIPE and VEGFR2 expression in 55 specimens from CRC patients. We also used HCT116 CRC cells and human umbilical vein endothelial cells (HUVECs) for in vitro experiments by stably transducing shTIPE and shRNA control lentivirus into HCT116 cells, detecting VEGFR2 expression after TIPE knockdown and repurposing the culture supernatant as conditioned medium to stimulate angiogenesis of HUVECs. In vivo experiments with chicken chorioallantoic membranes (CAMs) and a nude mouse matrix subcutaneous tumor model were performed to validate the effects of TIPE on angiogenesis. Additionally, we analyzed the expression and phosphorylation levels of PDK1 and blocked PDK1 expression using inhibitors to determine whether TIPE-induced changes in VEGFR2-mediated angiogenesis acted via the PI3K-Akt pathway. Results: We found that TIPE and VEGFR2 are highly expressed in CRC and act as oncogenes. TIPE knockdown also downregulated VEGFR2 expression, which resulted in simultaneous inhibition of cell proliferation, cell migration and angiogenesis. Then, in vivo experiments further demonstrated that TIPE promotes angiogenesis in CRC. Finally, we found that TIPE promotes VEGFR2-mediated angiogenesis by upregulating PDK1 expression and phosphorylation and that blocking PDK1 expression can inhibit this process. Conclusion: TIPE promotes angiogenesis in CRC by regulating the expression of VEGFR2, which may be a target for antiangiogenic cancer therapy.


Assuntos
Neoplasias Colorretais/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neovascularização Patológica/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/fisiologia
7.
Nano Lett ; 19(3): 1719-1727, 2019 03 13.
Artigo em Inglês | MEDLINE | ID: mdl-30724087

RESUMO

Protein nanocages are promising multifunctional platforms for nanomedicine owing to the ability to decorate their surfaces with multiple functionalities through genetic and/or chemical modification to achieve desired properties for therapeutic and diagnostic purposes. Here, we describe a model antigen (OVA peptide) that was conjugated to the surface of a naturally occurring hepatitis B core protein nanocage (HBc NC) by genetic modification. The engineered OVA-HBc nanocages (OVA-HBc NCs), displaying high density repetitive array of epitopes in a limited space by self-assembling into symmetrical structure, not only can induce bone marrow derived dendritic cells (BMDC) maturation effectively but also can be enriched in the draining lymph nodes. Naïve C57BL/6 mice immunized with OVA-HBc NCs are able to generate significant and specific cytotoxic T lymphocyte (CTL) responses. Moreover, OVA-HBc NCs as a robust nanovaccine can trigger preventive antitumor immunity and significantly delay tumor growth. When combined with a low-dose chemotherapy drug (paclitaxel), OVA-HBc NCs could specifically inhibit progression of an established tumor. Our findings support HBc-based nanocages with modularity and scalability as an attractive nanoplatform for combination cancer immunotherapy.


Assuntos
Antígenos de Neoplasias/administração & dosagem , Antígenos do Núcleo do Vírus da Hepatite B/imunologia , Nanoconjugados/administração & dosagem , Neoplasias/terapia , Animais , Antígenos de Neoplasias/imunologia , Bioengenharia/métodos , Proliferação de Células/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Epitopos/genética , Epitopos/imunologia , Hepatite B/imunologia , Antígenos do Núcleo do Vírus da Hepatite B/administração & dosagem , Humanos , Imunoterapia/métodos , Camundongos Endogâmicos C57BL , Neoplasias/imunologia , Linfócitos T Citotóxicos/efeitos dos fármacos , Linfócitos T Citotóxicos/imunologia
8.
Int J Clin Exp Pathol ; 12(9): 3376-3383, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31934180

RESUMO

Fat mass and obesity-associated protein (FTO) has been well known for a pivotal role in regulation of fat mass, adipogenesis and body weight. In recent years, increasing studies revealed a strong association between FTO and various types of cancer. Its role in human hepatocellular carcinoma, however, remains unclear. We aimed at investigating the expression pattern and clinical significance of FTO in hepatocellular carcinoma. We found that FTO mRNA levels were significantly lower in hepatocellular carcinoma tissues. Immunohistochemical analysis showed the expression of FTO was reduced in the nuclei in hepatocellular carcinoma, and was associated with AFP level (P < 0.001), tumor size (P < 0.001), metastasis (P = 0.025) and vascular invasion (P < 0.001). Patients with decreased FTO expression had a shorter overall and tumor-free survival time (P = 0.004 and P = 0.006) than those with normal FTO expression. Cox's proportional hazard regression model revealed that reduced expression of FTO was a risk factor associated with the prognosis of HCC patients (P = 0.022). These results indicated that decreased FTO expression is correlated with clinicopathological factors, implying that FTO could be a vital predictor of poor outcome in HCC patients and serves as a novel biomarker for HCC.

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