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2.
Virol Sin ; 2022 Feb 18.
Artigo em Inglês | MEDLINE | ID: mdl-35527227

RESUMO

Multiple new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have constantly emerged, as the delta and omicron variants, which have developed resistance to currently gained neutralizing antibodies. This highlights a critical need to discover new therapeutic agents to overcome the variants mutations. Despite the availability of vaccines against coronavirus disease 2019 (COVID-19), the use of broadly neutralizing antibodies has been considered as an alternative way for the prevention or treatment of SARS-CoV-2 variants infection. Here, we show that the nasal delivery of two previously characterized broadly neutralizing antibodies (F61 and H121) protected K18-hACE2 mice against lethal challenge with SARS-CoV-2 variants. The broadly protective efficacy of the F61 or F61/F121 cocktail antibodies was evaluated by lethal challenge with the wild strain (WIV04) and multiple variants, including beta (B.1.351), delta (B.1.617.2), and omicron (B.1.1.529) at 200 or 1000 TCID50, and the minimum antibody administration doses (5-1.25 â€‹mg/kg body weight) were also evaluated with delta and omicron challenge. Fully prophylactic protections were found in all challenged groups with both F61 and F61/H121 combination at the administration dose of 20 â€‹mg/kg body weight, and corresponding mice lung viral RNA showed negative, with almost all alveolar septa and cavities remaining normal. Furthermore, low-dose antibody treatment induced significant prophylactic protection against lethal challenge with delta and omicron variants, whereas the F61/H121 combination showed excellent results against omicron infection. Our findings indicated the potential use of broadly neutralizing monoclonal antibodies as prophylactic and therapeutic agent for protection of current emerged SARS-CoV-2 variants infection.

3.
J Environ Manage ; 312: 114856, 2022 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-35325739

RESUMO

To suppress the electron-hole recombination and enhance the electron transfer on carbon nitride, an Fe-doped porous carbon nitride catalyst (Fe/SCN) was synthesized via supramolecular self-assembly method and applied in heterogeneous Fenton activation for efficient tetracycline (TC) degradation. Various characterizations revealed that the catalyst exhibited excellent visible light capture performance and electron transfer capacity. The highest degradation efficiency and mineralization rate of TC (10 mg L-1) were achieved under neutral condition (90.3% and 61.2%, respectively) with the leaching of Fe less than 14 µg L-1. Free radical quenching experiments and spin-resonance spectroscopy characterizations revealed the dominating role of OH in TC degradation, and density functional theory calculation confirmed the formation of Fe-NX and revealed the interaction between Fe sites and H2O2. Three possible pathways of TC degradation were proposed, and the biological inhibition test revealed the potential of Fe/SCN/H2O2 system to reduce environmental risks caused by TC. This work provides a new insight into the design of metal-doped heterogeneous Fenton catalyst for the efficient degradation of antibiotic contaminants in water.


Assuntos
Peróxido de Hidrogênio , Tetraciclina , Antibacterianos , Catálise , Peróxido de Hidrogênio/química , Luz
5.
J Colloid Interface Sci ; 615: 79-86, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35124508

RESUMO

Despite the fact that solid-state electrolytes have attracted broad research interests, the limited ion transfer and high interface impedance restrain their application in high-performance batteries with high cyclic stability and power density. Here, a new quasi-solid-state polymer electrolyte containing lightweight semiconducting hydrogenated borophene (HB) nanosheets, ionic liquids, and poly (ethylene oxide) is reported. The cyclic overpotential of the Li-Li symmetrical battery is about 65 mV lower than that of HB-free quasi-solid-state electrolyte, demonstrating the lower interface impedance. The interaction between lithium-ion and ethylene-oxide chains decreases owing to the existence of HB nanosheets and ionic liquids, which facilitates lithium-ion diffusion. The lithium bis(trifluoromethanesulfonyl)imide molecule surface adsorption at the HB nanosheets enhances the dissociation of lithium ions, and thus the matched lithium iron phosphate/Li full cell delivers the acceptable rate performance up to 5C. This work provides a new filler candidate to enhance the ionic conductivity of quasi-solid-state electrolytes that may facilitate to construct the high-performance HB nanosheets and ionic liquids-based lithium metal batteries.

6.
Phytomedicine ; 98: 153933, 2022 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-35121394

RESUMO

BACKGROUND: Senescence leads to permanent cell-cycle arrest and is a potential target for cancer therapy. Andrographolide (AD) is a diterpene lactone isolated from Traditional Chinese Medicine (TCM) Andrographis paniculate, which has been used as an anti-inflammatory drug in clinical practice with the potential to target senescence in recalcitrant lung cancer. PURPOSE: To determine whether AD can induce senescence in human lung adenocarcinoma in vitro and in vivo and to elucidate the underlying mechanisms. METHODS: SA-ß-Gal staining was used to detect the expression of senescence-associated ß-galactosidase (SA-ß-Gal) in human lung adenocarcinoma cells A549 and NCI-H1795. DNA damage was examined by the detection of γH2AX foci. Cell cycle was analyzed by flow cytometry. Cancer cell proliferation was determined by ATPlite assay and clonogenic survival assay in vitro. Tumor growth was determined in a mouse model of A549. The expression level of proteins and mRNA was estimated by Western blotting and Quantitative RT-PCR, respectively. Small interfering RNA (siRNA) was used to knock down p21, p27 and p53 to explore the potential mechanism of AD-induced senescence in human lung adenocarcinoma cells. RESULTS: AD-induced A549 and NCI-H1795 cell senescence determined by increased cell size, flattened morphology, DNA damage, cell cycle arrest as well as the increased expression of ß-galactosidase. AD inhibited cell proliferation in lung cells in vitro and lung cells xenograft growth in nude mice. p21 and p27, the major cell cycle regulators and mediators of senescence, were upregulated at the protein level in AD-treated A549 lung adenocarcinoma in vitro and in vivo. Further studies demonstrated that AD induced cell senescence via p53/p21 and Skp2/p27. CONCLUSION: In the present study, we found that the primary anti-inflammatory drug AD could have a potential antitumor effect in lung cancer. We demonstrated that AD induced lung adenocarcinoma senescence in vitro and in vivo via p53/p21 and Skp2/p27 for the first time. AD is therefore a promising senescence-inducing therapeutic for recalcitrant human lung adenocarcinoma.

7.
J Hazard Mater ; 423(Pt A): 127039, 2022 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-34481385

RESUMO

In this study, a copper-based catalyst (CuCN) with CuNx active sites highly dispersed in a porous carbon nitride matrix was synthesized and applied to a heterogeneous photo-assisted Photo-Fenton (PF) system to degrade tetracycline (TET). The results showed that the CuCN/PF system degraded up to 93.6% of TET within 60 min for ultrapure water matrix under the best experimental conditions, and more than 70% of TET for both river and lake water matrix. Toxicological tests suggested that the environmental risk caused by TET can be effectively inhibited by the CuCN/PF system. The good visible-light response and charge transport abilities of CuCN catalyst were identified in photoelectrochemical experiments. Free radical scavenging experiments and electron paramagnetic resonance (EPR) spectroscopy indicated that the active species in the degradation process were·OH, h+,·O2- and 1O2. Density functional theory (DFT) calculations revealed the positive effect of CuNx sites in CuCN on the formation of hydroxyl radicals by activating H2O2. This work will provide a new insight for the development of high-efficiency heterogeneous catalysts in wastewater environmental remediation.


Assuntos
Peróxido de Hidrogênio , Tetraciclina , Antibacterianos , Catálise , Radical Hidroxila
8.
Front Pharmacol ; 12: 668887, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34630073

RESUMO

Jujuboside B (JB) is one of the main biologically active ingredients extracted from Zizyphi Spinosi Semen (ZSS), a widely used traditional Chinese medicine for treating insomnia and anxiety. Breast cancer is the most common cancer and the second leading cause of cancer-related death in women worldwide. The purpose of this study was to examine whether JB could prevent breast cancer and its underlying mechanism. First, we reported that JB induced apoptosis and autophagy in MDA-MB-231 and MCF-7 human breast cancer cell lines. Further mechanistic studies have revealed that JB-induced apoptosis was mediated by NOXA in both two cell lines. Moreover, the AMPK signaling pathway plays an important role in JB-induced autophagy in MCF-7. To confirm the anti-breast cancer effect of JB, the interaction of JB-induced apoptosis and autophagy was investigated by both pharmacological and genetic approaches. Results indicated that autophagy played a pro-survival role in attenuating apoptosis. Further in vivo study showed that JB significantly suppressed the growth of MDA-MB-231 and MCF-7 xenografts. In conclusion, our findings indicate that JB exerts its anti-breast cancer effect in association with the induction of apoptosis and autophagy.

10.
Int J Oncol ; 59(5)2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34533200

RESUMO

Lactoferrin (Lf) is secreted by ectodermal tissue and has a structure similar to that of transferrin. Although Lf seems to be multifunctional, its main function is related to the natural defense system of mammals. The present review aims to highlight the major actions of Lf, including the regulation of cell growth, the inhibition of toxic compound formation, the removal of harmful free radicals and its important role in immune response regulation. Moreover, Lf has antibacterial, antiviral, antioxidant, anticancer and anti­inflammatory activities. In addition, the use of Lf for functionalization of drug nanocarriers, with emphasis on tumor­targeted drug delivery, is illustrated. Such effects serve as an important theoretical basis for its future development and application. In neurodegenerative diseases and the brains of elderly people, Lf expression is markedly upregulated. Lf may exert an anti­inflammatory effect by inhibiting the formation of hydroxyl free radicals. Through its antioxidant properties, Lf can prevent DNA damage, thereby preventing tumor formation in the central nervous system. In addition, Lf specifically activates the p53 tumor suppressor gene.


Assuntos
Adjuvantes Imunológicos/farmacologia , Lactoferrina/farmacologia , Neoplasias/prevenção & controle , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Nanotecnologia
11.
Viruses ; 13(8)2021 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-34452373

RESUMO

The development of rapid serological detection methods re urgently needed for determination of neutralizing antibodies in sera. In this study, four rapid methods (ACE2-RBD inhibition assay, S1-IgG detection, RBD-IgG detection, and N-IgG detection) were established and evaluated based on chemiluminescence technology. For the first time, a broadly neutralizing antibody with high affinity was used as a standard for the quantitative detection of SARS-CoV-2 specific neutralizing antibodies in human sera. Sera from COVID-19 convalescent patients (N = 119), vaccinated donors (N = 86), and healthy donors (N = 299) confirmed by microneutralization test (MNT) were used to evaluate the above methods. The result showed that the ACE2-RBD inhibition assay calculated with either ACE2-RBD binding inhibition percentage rate or ACE2-RBD inhibiting antibody concentration were strongly correlated with MNT (r ≥ 0.78, p < 0.0001) and also highly consistent with MNT (Kappa Value ≥ 0.94, p < 0.01). There was also a strong correlation between the two evaluation indices (r ≥ 0.99, p < 0.0001). Meanwhile, S1-IgG and RBD-IgG quantitative detection were also significantly correlated with MNT (r ≥ 0.73, p < 0.0001), and both methods were highly correlated with each other (r ≥ 0.95, p < 0.0001). However, the concentration of N-IgG antibodies showed a lower correlation with the MNT results (r < 0.49, p < 0.0001). The diagnostic assays presented here could be used for the evaluation of SARS-CoV-2 vaccine immunization effect and serological diagnosis of COVID-19 patients, and could also have guiding significance for establishing other rapid serological methods to surrogate neutralization tests for SARS-CoV-2.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Teste Sorológico para COVID-19/métodos , Vacinas contra COVID-19/imunologia , COVID-19/virologia , Imunoensaio/métodos , Medições Luminescentes/métodos , SARS-CoV-2/imunologia , COVID-19/sangue , COVID-19/imunologia , COVID-19/prevenção & controle , Teste Sorológico para COVID-19/instrumentação , Vacinas contra COVID-19/administração & dosagem , Humanos , SARS-CoV-2/genética , Vacinação
12.
Front Oncol ; 11: 666549, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34195076

RESUMO

Esophageal squamous cell carcinoma (ESCC) is a recalcitrant cancer. The Chinese herbal monomer fangchinoline (FCL) has been reported to have anti-tumor activity in several human cancer cell types. However, the therapeutic efficacy and underlying mechanism on ESCC remain to be elucidated. In the present study, for the first time, we demonstrated that FCL significantly suppressed the growth of ESCC both in vitro and in vivo. Mechanistic studies revealed that FCL-induced G1 phase cell-cycle arrest in ESCC which is dependent on p21 and p27. Moreover, we found that FCL coordinatively triggered Noxa-dependent intrinsic apoptosis and DR5-dependent extrinsic apoptosis by transactivating ATF4, which is a novel mechanism. Our findings elucidated the tumor-suppressive efficacy and mechanisms of FCL and demonstrated FCL is a potential anti-ESCC agent.

13.
Virol Sin ; 36(5): 934-947, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34224110

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has precipitated multiple variants resistant to therapeutic antibodies. In this study, 12 high-affinity antibodies were generated from convalescent donors in early outbreaks using immune antibody phage display libraries. Of them, two RBD-binding antibodies (F61 and H121) showed high-affinity neutralization against SARS-CoV-2, whereas three S2-target antibodies failed to neutralize SARS-CoV-2. Following structure analysis, F61 identified a linear epitope located in residues G446-S494, which overlapped with angiotensin-converting enzyme 2 (ACE2) binding sites, while H121 recognized a conformational epitope located on the side face of RBD, outside from ACE2 binding domain. Hence the cocktail of the two antibodies achieved better performance of neutralization to SARS-CoV-2. Importantly, these two antibodies also showed efficient neutralizing activities to the variants including B.1.1.7 and B.1.351, and reacted with mutations of N501Y, E484K, and L452R, indicated that it may also neutralize the recent India endemic strain B.1.617. The unchanged binding activity of F61 and H121 to RBD with multiple mutations revealed a broad neutralizing activity against variants, which mitigated the risk of viral escape. Our findings revealed the therapeutic basis of cocktail antibodies against constantly emerging SARS-CoV-2 variants and provided promising candidate antibodies to clinical treatment of COVID-19 patients infected with broad SARS-CoV-2 variants.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Humanos , Glicoproteína da Espícula de Coronavírus
14.
Methods Mol Biol ; 2326: 267-271, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34097275

RESUMO

Cadmium (Cd) is widespread in the soil, water, and atmosphere, so Cd toxicity to human can happen by breathing in air, drinking water, and eating food from plant grown in Cd-contaminated soil. Cd pollution draws a lot of attention from the scientific community and also regulatory agents and is researched widely by using both plant and animal system. In this protocol, the detection of cadmium (Cd) is described in soil and mature maize (Zea mays) plant with the atomic absorption spectrometer. The Cd uptake, translocation factor, and Cd health risk index are also introduced. The protocol can be modified slightly to measure Cd in different types of plants.


Assuntos
Cádmio/análise , Poluentes do Solo/análise , Solo/química , Zea mays/química , Transporte Biológico , Cádmio/metabolismo , Cádmio/toxicidade , Poluentes do Solo/metabolismo , Poluentes do Solo/toxicidade , Espectrofotometria Atômica/métodos , Zea mays/metabolismo
15.
J Hazard Mater ; 418: 126333, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34118537

RESUMO

Carbon-bridge-modified malonamide (MLD)/g-C3N4 (CN) was prepared by copolymerization of MLD with urea and melamine and loaded with Fe3O4 for the high-efficiency removal of tetracycline (TC) in water under photo-Fenton. The prepared catalysts were characterized by SEM, TEM, N2 adsorption-desorption analysis, XPS, XRD, and FTIR, which proved that the modification method successfully introduced the C bridge into the carbon nitride molecular system and increased the structural defects of the catalyst. The Carbon-bridge-modified MLD/CN/Fe3O4 also had good visible-light response and charge-separation and transport abilities in the photoelectrochemical test. Degradation results showed that the photo-Fenton degradation of TC reached 95.8%, and the mineralization rate was 55.7% within 80 min at 80 mM H2O2 dosage, 0.5 g/L catalyst dosage, and near-neutral pH by 0.8MLD/CN/Fe3O4. Moreover, the oxidation products and mineralization pathways of TC were explored by LC-MS. Toxicity analysis indicated low environmental threat of the intermediates in TC mineralization. EPR analysis and H2O2 decomposition efficiency analyses showed an improvement in the H2O2 decomposition performance of 0.8MLD/CN/Fe3O4. This work could provide a valuable insight for the application of heterogeneous photo-Fenton technology in wastewater treatment.


Assuntos
Carbono , Poluentes Químicos da Água , Catálise , Peróxido de Hidrogênio , Fenômenos Magnéticos , Tetraciclina , Poluentes Químicos da Água/análise
16.
Front Oncol ; 11: 671180, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33898327

RESUMO

The neddylation pathway is overactivated in esophageal cancer. Our previous studies indicated that inactivation of neddylation by the NAE inhibitor induced apoptosis and autophagy in cancer cells. Camptothecin (CPT), a well-known anticancer agent, could induce apoptosis and autophagy in cancer cells. However, whether CPT could affect the neddylation pathway and the molecular mechanisms of CPT-induced autophagy in esophageal cancer remains elusive. We found that CPT induced apoptosis and autophagy in esophageal cancer. Mechanistically, CPT inhibited the activity of neddylation and induced the accumulation of p-IkBa to block NF-κB pathway. Furthermore, CPT induced the generation of ROS to modulate the AMPK/mTOR/ULK1 axis to finally promote protective autophagy. In our study, we elucidate a novel mechanism of the NF-κB/AMPK/mTOR/ULK1 pathway in CPT-induced protective autophagy in esophageal cancer cells, which provides a sound rationale for combinational anti-ESCC therapy with CPT and inhibition AMPK/ULK1 pathway.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33802869

RESUMO

Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease and that is a severe threat to public health considering its high fatality and person-to-person transmission. In order to obtain an updated and deep understanding of the epidemiological characteristics of SFTS in mainland China, we used Pearson's chi-squared test to compare the fatality rate and demographic characteristics in different groups. Data were analyzed in R3.6.1 (R Development Core Team 2018), while the visualization was performed in ArcGIS 10 (ESRI, Redlands, CA, USA), and the statistical significance was set at p < 0.05. A total of 13,824 SFTS cases involving 8899 lab-confirmed cases and 4925 probable cases were reported and included in the epidemiological analysis. Our study found that the number of SFTS cases showed an increasing trend with a small decrease in the past three years. The laboratory-confirmed rate was about 64.4%, which varied between different years and areas. Although most cases (99.3%) were distributed in 7 provinces (Henan, Shandong, Anhui, Hubei, Liaoning, Zhejiang, and Jiangsu), the regional distribution of SFTS gradually expanded from 5 provinces in 2010 to 25 provinces by 2019, especially at the town level. The SFTS cases were mainly sporadic. A total of 96.5% occurred from April to October, and 93.3% of cases were concentrated in middle-aged and elderly people (40-84 years old). Farmers were the main high-risk population. Female cases were slightly more than male cases; however, there were differences between different provinces. The mortality rate showed an increasing trend with age. Overall, the SFTS cases were mainly middle-aged and elderly farmers that sporadically distributed throughout seven provinces with a spatially expanding trend. The laboratory-confirmed rate varied in different years and provinces, which implied that the diagnosis and report criteria for SFTS should be further updated and unified in order to get a better understanding of its epidemiological characteristics and provide scientific data for SFTS control.


Assuntos
Infecções por Bunyaviridae , Doenças Transmissíveis Emergentes , Phlebovirus , Febre Grave com Síndrome de Trombocitopenia , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções por Bunyaviridae/epidemiologia , China/epidemiologia , Cidades , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Sci Rep ; 11(1): 6811, 2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33762651

RESUMO

High rate of cardiovascular disease (CVD) has been reported among patients with coronavirus disease 2019 (COVID-19). Importantly, CVD, as one of the comorbidities, could also increase the risks of the severity of COVID-19. Here we identified phospholipase A2 group VII (PLA2G7), a well-studied CVD biomarker, as a hub gene in COVID-19 though an integrated hypothesis-free genomic analysis on nasal swabs (n = 486) from patients with COVID-19. PLA2G7 was further found to be predominantly expressed by proinflammatory macrophages in lungs emerging with progression of COVID-19. In the validation stage, RNA level of PLA2G7 was identified in nasal swabs from both COVID-19 and pneumonia patients, other than health individuals. The positive rate of PLA2G7 were correlated with not only viral loads but also severity of pneumonia in non-COVID-19 patients. Serum protein levels of PLA2G7 were found to be elevated and beyond the normal limit in COVID-19 patients, especially among those re-positive patients. We identified and validated PLA2G7, a biomarker for CVD, was abnormally enhanced in COVID-19 at both nucleotide and protein aspects. These findings provided indications into the prevalence of cardiovascular involvements seen in patients with COVID-19. PLA2G7 could be a potential prognostic and therapeutic target in COVID-19.


Assuntos
1-Alquil-2-acetilglicerofosfocolina Esterase/metabolismo , COVID-19/metabolismo , Doenças Cardiovasculares/metabolismo , Macrófagos/metabolismo , 1-Alquil-2-acetilglicerofosfocolina Esterase/sangue , 1-Alquil-2-acetilglicerofosfocolina Esterase/genética , Biomarcadores/metabolismo , COVID-19/epidemiologia , COVID-19/imunologia , COVID-19/patologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/virologia , China/epidemiologia , Mineração de Dados/métodos , Humanos , Macrófagos/imunologia , Macrófagos/patologia , Polimorfismo de Nucleotídeo Único , SARS-CoV-2/isolamento & purificação , Ativação Transcricional , Regulação para Cima
19.
Cancer Biol Med ; 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33733647

RESUMO

OBJECTIVE: The hyperactivated neddylation pathway plays an important role in tumorigenesis and is emerging as a promising anticancer target. We aimed to study whether NEDD8 (neural precursor cell expressed, developmentally down-regulated 8) might serve as a therapeutic target in esophageal squamous cell carcinoma (ESCC). METHODS: The clinical relevance of NEDD8 expression was evaluated by using The Cancer Genome Atlas (TCGA) database and tissue arrays. NEDD8-knockdown ESCC cells generated with the CRISPR/Cas9 system were used to explore the anticancer effects and mechanisms. Quantitative proteomic analysis was used to examine the variations in NEDD8 knockdown-induced biological pathways. The cell cycle and apoptosis were assessed with fluorescence activated cell sorting. A subcutaneous-transplantation mouse tumor model was established to investigate the anticancer potential of NEDD8 silencing in vivo. RESULTS: NEDD8 was upregulated at both the mRNA and protein expression levels in ESCC, and NEDD8 overexpression was associated with poorer overall patient survival (mRNA level: P = 0.028, protein level: P = 0.026, log-rank test). Downregulation of NEDD8 significantly suppressed tumor growth both in vitro and in vivo. Quantitative proteomic analysis revealed that downregulation of NEDD8 induced cell cycle arrest, DNA damage, and apoptosis in ESCC cells. Mechanistic studies demonstrated that NEDD8 knockdown led to the accumulation of cullin-RING E3 ubiquitin ligases (CRLs) substrates through inactivation of CRLs, thus suppressing the malignant phenotype by inducing cell cycle arrest and apoptosis in ESCC. Rescue experiments demonstrated that the induction of apoptosis after NEDD8 silencing was attenuated by DR5 knockdown. CONCLUSIONS: Our study elucidated the anti-ESCC effects and underlying mechanisms of NEDD8 knockdown, and validated NEDD8 as a potential target for ESCC therapy.

20.
Front Cell Dev Biol ; 9: 617134, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33553178

RESUMO

Rho family GTPase RhoB is the critical signaling component controlling the inflammatory response elicited by pro-inflammatory cytokines. However, the underlying mechanisms of RhoB degradation in inflammatory response remain unclear. In this study, for the first time, we identified that TNFAIP1, an adaptor protein of Cullin3 E3 ubiquitin ligases, coordinated with Cullin3 to mediate RhoB degradation through ubiquitin proteasome system. In addition, we demonstrated that downregulation of TNFAIP1 induced the expression of pro-inflammatory cytokines IL-6 and IL-8 in TNFα-stimulated hepatocellular carcinoma cells through the activation of p38/JNK MAPK pathway via blocking RhoB degradation. Our findings revealed a novel mechanism of RhoB degradation and provided a potential strategy for anti-inflammatory intervention of tumors by targeting TNFAIP1-RhoB axis.

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