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The collective modes of the superconducting order parameter fluctuation can provide key insights into the nature of the superconductor. Recently, a family of superconductors has emerged in non-magnetic kagome materials AV3Sb5 (A = K, Rb, Cs), exhibiting fertile emergent phenomenology. However, the collective behaviors of Cooper pairs have not been studied. Here, we report a distinct collective mode in CsV3-xTaxSb5 using scanning tunneling microscope/spectroscopy. The spectral line-shape is well-described by one isotropic and one anisotropic superconducting gap, and a bosonic mode due to electron-mode coupling. With increasing x, the two gaps move closer in energy, merge into two isotropic gaps of equal amplitude, and then increase synchronously. The mode energy decreases monotonically to well below 2 Δ and survives even after the charge density wave order is suppressed. We propose the interpretation of this collective mode as Leggett mode between different superconducting components or the Bardasis-Schrieffer mode due to a subleading superconducting component.
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As one of the most important food crops in the world, rice yield is directly related to national food security. Lodging is one of the most important factors restricting rice production, and the cultivation of rice varieties with lodging resistance is of great significance in rice breeding. The lodging resistance of rice is directly related to the mechanical strength of the stalks. In this paper, we reviewed the cell wall structure, its components, and its genetic regulatory mechanism, which improved the regulatory network of rice stalk mechanical strength. Meanwhile, we analyzed the new progress in genetic breeding and put forward some scientific problems that need to be solved in this field in order to provide theoretical support for the improvement and application of rice breeding.
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The manuscript aimed to study the immune function maintenance effect of Achyranthes bidentata polysaccharides (ABPs). The mice were divided into the control group, cyclophosphamide-induced (CTX) group, and ABPs-treated (ABP) group. The results showed that, compared with the CTX group, ABPs could significantly improve the spleen index and alleviate the pathological changes in immune organs. Ex vivo study of whole spleen cells, the levels of interleukin-2 (IL-2), interleukin-6 (IL-6), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) were increased. The proliferation of lymphocytes and the proportion of CD3+CD4+ Th cells in peripheral blood mononuclear cells were increased. The transcription of GATA-3, Foxp3, and ROR γ t were decreased, while the transcription of T-bet was increased. The transcriptome sequencing analysis showed that the differentially expressed genes (DEGs) caused by ABPs-treated were mostly downregulated in CTX-induced mice. The Th2-related genes were significantly enriched in DEGs, with representative genes, including Il4, II13, Il9, etc., while increasing the expression of immune effector genes simultaneously, including Ccl3, Ccr5, and Il12rb2. It was suggested that ABPs possibly regulated the balance of cytokines in helper T cells to ameliorate the immune function of CTX-induced mice.
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Achyranthes , Citocinas , Camundongos , Animais , Leucócitos Mononucleares , Linfócitos T Auxiliares-Indutores , Polissacarídeos/farmacologia , Ciclofosfamida/efeitos adversos , Receptores de Interleucina-12RESUMO
Atomically precise defect engineering is essential to manipulate the properties of emerging topological quantum materials for practical quantum applications. However, this remains challenging due to the obstacles in modifying the typically complex crystal lattice with atomic precision. Here, we report the atomically precise engineering of the vacancy-localized spin-orbit polarons in a kagome magnetic Weyl semimetal Co3Sn2S2, using scanning tunneling microscope. We achieve the step-by-step repair of the selected vacancies, leading to the formation of artificial sulfur vacancies with elaborate geometry. We find that that the bound states localized around these vacancies undergo a symmetry dependent energy shift towards Fermi level with increasing vacancy size. As the vacancy size increases, the localized magnetic moments of spin-orbit polarons become tunable and eventually become itinerantly negative due to spin-orbit coupling in the kagome flat band. These findings provide a platform for engineering atomic quantum states in topological quantum materials at the atomic scale.
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SMARCA4-deficient gastric carcinoma has been reported sporadically since 2016. Only 29 patients have been reported; nevertheless, it is aggressive and highly malignant with poor outcomes. It has an immunohistochemical phenotype showing loss of SMARCA4 expression and can be accompanied by codeletion of other switch/sucrose non-fermentable chromatin-remodeling complex subunits. Microscopically, it displays high-grade undifferentiated histological morphology with rhabdoid cell differentiation. Rarely does the tumor contain a purely or partly adenocarcinoma component. Here, we report two cases to demonstrate these unusual morphologies analyzed using morphological and immunohistochemical techniques. In addition, there is a lack of research on the classification of these morphologies. Therefore, our report will aid the diagnosis and classification of SMARCA4-deficient gastric carcinoma.
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Corporate energy consumption and emissions are major contributors to pollution and greenhouse gas emissions. Therefore, corporate energy conservation and emission reduction are essential for sustainable development and low-carbon transformation in China. With pressing global environmental issues and the mounting pressure for carbon neutrality, it is increasingly important for firms to disclose environmental information. However, research on the relationship and mechanisms between corporate environmental information disclosure (EID) and corporate performance is insufficient. This study examines the effect of EID on corporate environmental performance (EP) and financial performance (FP) using a two-way fixed-effect model. For this purpose, this study considers the panel data of 1125 Chinese A-share listed companies from 2009 to 2021. Additionally, we explore the underlying mechanisms using mediation models. The results reveal that EID can significantly improve corporate performance through green innovation (GI). Moreover, EID can enhance corporate GI, which improves the financial performance of high-polluting firms and the environmental performance of non-high-polluting firms. According to these results, it is imperative to continuously improve corporate EID systems and encourage GI in enterprises. Thus, firms should take the initiative to disclose environmental information. There is a pressing need to enhance the effectiveness of the capital market, therefore, firms with higher levels of EID and better environmental performance can gain greater benefits.
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Swertia bimaculata (SB) is a medicinal herb in China having an array of therapeutic and biological properties. This study aimed to explore the attenuating effect of SB on carbon tetrachloride (CCl4) induced hepato-toxicity by regulation of gut microbiome in ICR mice. For this purpose, CCl4 was injected intraperitoneally in different mice groups (B, C, D and E) every 4th day for a period of 47 days. Additionally, C, D, and E groups received a daily dose (50 mg/kg, 100 mg/kg, and 200 mg/kg respectively) of Ether extract of SB via gavage for the whole study period. The results of serum biochemistry analysis, ELISA, H&E staining, and sequencing of the gut microbiome, indicated that SB significantly alleviates the CCl4-induced liver damage and hepatocyte degeneration. The serum levels of alanine transaminase, aspartate aminotransferase, malondialdehyde, interleukin 1 beta and tumor necrosis factor-alpha were significantly lower in SB treated groups compared to control while levels of glutathione peroxidase were raised. Also, the sequencing data indicate that supplementation with SB could restore the microbiome and its function in CCl4-induced variations in intestinal microbiome of mice by significantly downregulating the abundances of pathogenic intestinal bacteria species including Bacteroides, Enterococcus, Eubacterium, Bifidobacterium while upregulating the levels of beneficial bacteria like Christensenella in the gut. In conclusion, we revealed that SB depicts a beneficial effect against hepatotoxicity induced by CCl4 in mice through the remission of hepatic inflammation and injury, through regulation of oxidative stress, and by restoring gut microbiota dysbiosis.
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Doença Hepática Induzida por Substâncias e Drogas , Microbioma Gastrointestinal , Hepatopatias , Swertia , Camundongos , Animais , Fígado , Swertia/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Camundongos Endogâmicos ICR , Estresse Oxidativo , Aspartato Aminotransferases/metabolismo , Alanina Transaminase/metabolismo , IntestinosRESUMO
Kagome lattices of various transition metals are versatile platforms for achieving anomalous Hall effects, unconventional charge-density wave orders and quantum spin liquid phenomena due to the strong correlations, spin-orbit coupling and/or magnetic interactions involved in such a lattice. Here, we use laser-based angle-resolved photoemission spectroscopy in combination with density functional theory calculations to investigate the electronic structure of the newly discovered kagome superconductor CsTi3Bi5, which is isostructural to the AV3Sb5 (A = K, Rb or Cs) kagome superconductor family and possesses a two-dimensional kagome network of titanium. We directly observe a striking flat band derived from the local destructive interference of Bloch wave functions within the kagome lattice. In agreement with calculations, we identify type-II and type-III Dirac nodal lines and their momentum distribution in CsTi3Bi5 from the measured electronic structures. In addition, around the Brillouin zone centre, [Formula: see text] nontrivial topological surface states are also observed due to band inversion mediated by strong spin-orbit coupling.
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Periodontitis is a chronic inflammatory disease induced by subgingival microbial dysbiosis, characterised by inflammation of the soft tissues of the periodontium and progressive loss of alveolar bone. Limosilactobacillus fermentum CCFM1139 is a probiotic with the potential to relieve periodontitis in vitro and in vivo. Due to the cost of active strain in production applications, we considered the effectiveness of bacterial components and metabolites in alleviating experimental periodontitis. Therefore, this study investigated the effect of heat-inactivated Limosilactobacillus fermentum CCFM1139 and its supernatant in the development of experimental periodontitis through animal experiments. The results showed that active, heat-inactivated Limosilactobacillus fermentum CCFM1139 and its supernatant all significantly reduced IL-1ß levels in gingival tissue and serum (p < 0.05). Micro-computed tomography (micro CT) analysis showed that the active and heat-inactivated Limosilactobacillus fermentum CCFM1139 reduced alveolar bone loss in rats with periodontitis by 25.6% and 15.9% respectively (p < 0.05), with no change in percentage of bone volume (p > 0.05). In histomorphometric analysis, active Limosilactobacillus fermentum CCFM1139 showed better results in reducing alveolar bone loss and reducing inflammatory cell recruitment at the second molar. In addition, there was no significant difference in the number of tartrate-resistant acid phosphatase (TRAP) positive cells after in all experimental groups (p > 0.05). Therefore, heat-inactivated Limosilactobacillus fermentum CCFM1139 or its supernatant also have the ability to relieve periodontitis, and their alleviating effect may focus on the regulation of inflammatory response.
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Perda do Osso Alveolar , Limosilactobacillus fermentum , Periodontite , Ratos , Animais , Microtomografia por Raio-X , Temperatura Alta , Modelos Animais de DoençasRESUMO
ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine believes that "blood fever" is an important cause of psoriasis. Fufang Shengdi mixture (FFSD), based on the Hongban Decoction, is composed of Rehmannia glutinosa (Gaertn.) DC., Raw gypsum (Chinese: Sheng Shi Gao), and Lonicera japonica Thunb (Caprifoliaceae). FFSD has effects on nourishing Yin, clearing heat, connecting collaterals, and cooling blood. In modern medical explanation, FFSD has the effects of anti-inflammatory and immunosuppression. Our study proved that FFSD can suppress immunity and ameliorate the symptoms of imiquimod-induced psoriasis in mice. AIM OF THE STUDY: This study evaluated the efficacy and possible mechanism of FFSD in psoriasis mice. METHODS AND MATERIALS: First, the main components of FFSD were analyzed using high-performance liquid chromatography-tandem high-resolution mass spectrometry (HPLC-HRMS). An imiquimod (IMQ)-induced psoriasis mouse model was used to evaluate the efficacy of FFSD orally. Psoriasis area and severity index (PASI) scores were recorded throughout the course of the mice to reflect the severity of psoriasis. Hematoxylin-eosin staining was used to observe the pathological changes in skin lesions. Enzyme-linked immunosorbent assay (ELISA) was performed to test the level of IFN-γ and TNF-α in plasma. To further investigate the immunopharmacological effect of FFSD, we used chicken ovalbumin (OVA) to induce immunoreaction in mice. ELISA was used to detect the levels of anti-OVA antibody, IFN-γ and TNF-α in mice. Flow cytometry was performed to quantify the ratio of cell types in peripheral blood mononuclear cells (PBMCs) to evaluate the effect of FFSD on immunosuppression. Proteomics and bioinformatics analyzes were performed to find the regulation pathway of the immunosuppressive effect of FFSD. Finally, quantitative PCR (qPCR) and immunohistochemistry were used to measure the upregulation of Annexin-A proteins (ANXAs) in the skin lesion tissue of IMQ-induced mouse. RESULTS: On the basis of knowing the composition of FFSD, we first proved the efficacy of FFSD in alleviating IMQ-induced psoriasis in mice. Second, we further clarified the pharmacological effect of FFSD on immunosuppression via OVA-induced mice. Subsequently, it was found that the significant up-regulation of ANXAs was caused by FFSD through proteomics analysis, and the finding was proved in the IMQ-induced psoriasis mouse model. CONCLUSIONS: This study elucidates the immunosuppressive pharmacological effect of FFSD on improving psoriasis through up-regulating ANXAs.
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Dermatite , Psoríase , Dermatopatias , Animais , Camundongos , Imiquimode , Fator de Necrose Tumoral alfa/metabolismo , Leucócitos Mononucleares/metabolismo , Anexinas/metabolismo , Psoríase/induzido quimicamente , Psoríase/tratamento farmacológico , Pele/patologia , Dermatopatias/metabolismo , Inflamação/patologia , Camundongos Endogâmicos BALB C , Modelos Animais de DoençasRESUMO
Background: Gastric adenocarcinoma (GAC) is highly heterogeneous and closely related to colorectal cancer (CRC) both molecularly and functionally. GAC is currently subtyped using a system developed by TCGA. However, with the emergence of immunotherapies, this system has failed to identify suitable treatment candidates. Methods: Consensus molecular subtypes (CMSs) developed for CRC were used for molecular subtyping in GAC based on public expression cohorts, including TCGA, ACRG, and a cohort of GAC patients treated with the programmed cell death 1 (PD-1) inhibitor pembrolizumab. All aspects of each subtype, including clinical outcome, molecular characteristics, oncogenic pathway activity, and the response to immunotherapy, were fully explored. Results: CMS classification was efficiently applied to GAC. CMS4, characterized by EMT activation, stromal invasion, angiogenesis, and the worst clinical outcomes (median OS 24.2 months), was the predominant subtype (38.8%~44.3%) and an independent prognostic indicator that outperformed classical TCGA subtyping. CMS1 (20.9%~21.5%) displayed hypermutation, low SCNV, immune activation, and best clinical outcomes (median OS > 120 months). CMS3 (17.95%~25.7%) was characterized by overactive metabolism, KRAS mutation, and intermediate outcomes (median OS 85.6 months). CMS2 (14.6%~16.3%) was enriched for WNT and MYC activation, differentiated epithelial characteristics, APC mutation, lack of ARID1A, and intermediate outcomes (median OS 48.7 months). Notably, CMS1 was strongly correlated with immunotherapy biomarkers and favorable for the anti-PD-1 drug pembrolizumab, whereas CMS4 was poorly responsive but became more sensitive after EMT-based stratification. Conclusions: Our study reveals the practical utility of CMS classification for GAC to improve clinical outcomes and identify candidates who will respond to immunotherapy.
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In this study, a pH-responsive controlled-release mesoporous silica nanoparticle (MSN) formulation was developed. The MSNs were functionalized with a histidine (His)-tagged targeting peptide (B3int) through an amide bond, and loaded with an anticancer drug (cisplatin (CP)) and a lysosomal destabilization mediator (chloroquine (CQ)). Cu2+ was then used to seal the pores of the MSNs via chelation with the His-tag. The resultant nanoparticles showed pH-responsive drug release, and could effectively target tumor cells via the targeting effect of B3int. The presence of CP and Cu2+ permits reactive oxygen species to be generated inside cells; thus, the chemotherapeutic effect of CP is augmented by chemodynamic therapy. In vitro and in vivo experiments showed that the nanoparticles are able to effectively kill tumor cells. An in vivo cancer model revealed that the nanoparticles increase apoptosis in tumor cells, and thereby diminish the tumor volume. No off-target toxicity was noted. It thus appears that the functionalized MSNs developed in this work have great potential for targeted, synergistic anticancer therapies.
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In this work, a novel layered double hydroxide (LDH)-based multifunctional nanoplatform was built for synergistic photothermal therapy (PTT)/chemotherapy. The platform was modified using the peptide B3int to target cancer cells with overexpression of integrin αvß3. Indocyanine green (ICG) and doxorubicin (DOX) were loaded into the nanocarrier (LDH-PEG-B3int NPs) to form a system having a high drug loading (18.62%) and a remarkable photothermal conversion efficiency of 25.38%. It also showed pH-responsive and near-infrared (NIR)-triggered DOX release. In vitro and in vivo studies indicated that the anti-tumor activity of the combined delivery system was significantly higher than that of a single delivery system. This co-delivery nanosystem may be helpful for future application in the clinical treatment of cancer.
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Hipertermia Induzida , Nanopartículas , Doxorrubicina/farmacologia , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Hidróxidos , Fototerapia , Terapia FototérmicaRESUMO
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.
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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.
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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.
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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 HomólogoAssuntos
Neoplasias Colorretais/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , MAP Quinase Quinase 3/genética , Metaloproteinase 9 da Matriz/genética , Proliferação de Células/genética , Neoplasias Colorretais/patologia , Células HCT116 , Humanos , Metaloproteinase 1 da Matriz/genética , NF-kappa B/genética , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Metástase Neoplásica , Transdução de Sinais/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genéticaRESUMO
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.
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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.
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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/fisiologiaRESUMO
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.