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1.
Eur J Pharmacol ; 912: 174617, 2021 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-34748770

RESUMO

Salidroside has been shown to exert neuroprotective effects against hypoxia. However, its mitochondrial protective mechanisms still remain elusive. The present study aimed to explore the mitochondrial protection of salidroside on PC12 cells and the involved mechanisms. The hypoxic injury of PC12 cells was triggered by CoCl2 stimulus. The contents of LDH release, SOD, GSH-PX, Na+-K+-ATPase, ATP, NAD+ and NADH were determined by using commercial biochemical kits. Clark-type oxygen electrode and Seahorse XFe24 analyzer were employed to evaluate cell respiration and measure oxygen consumption rate (OCR), respectively. Mitochondrial swelling and mitochondrial membrane potential (MMP) were measured by using isolated mitochondria from the brain tissue of mice. The proteins expression of cleaved Caspase-3, HIF-1α, ISCU1/2, COX10 and PFKP were tested by immunofluorescence and Western blot. While the genes expression of Caspase-3, HIF-1α, ISCU1/2, COX10 and miR-210 were tested by quantitative real-time PCR (qRT-PCR) analysis. Salidroside alleviated CoCl2-induced oxidative stress in PC12 cells as evidenced by increased cell viability, decreased LDH release and elevated GSH-PX and SOD activities. Salidroside could inhibit apoptosis by suppressing the level of cleaved Caspase-3 and Caspase-3. The enhanced mitochondrial energy synthesis by salidroside treatment was evidenced by the increases of Na+-K+-ATPase activity, ATP content, NAD+/NADH ratio, cellular respiration and OCR. In addition, salidroside could reduce mitochondrial swelling and MMP dissipation in isolated mitochondria. The results of immunofluorescence, Western blot and qRT-PCR analyses further revealed that salidroside raised the level of HIF-1α, ISCU1/2, COX10, and miR-210. Collectively, salidroside can reverse CoCl2-simulated hypoxia injury in PC12 cells partly by mitochondrial protection via inhibiting oxidative stress event, anti-apoptosis and enhancing mitochondrial energy synthesis.

2.
Cell Death Dis ; 12(11): 1045, 2021 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732698

RESUMO

Rapid adaptation to a hypoxic environment is an unanswered question that we are committed to exploring. At present, there is no suitable strategy to achieve rapid hypoxic adaptation. Here, we demonstrate that fasting preconditioning for 72 h reduces tissue injuries and maintains cardiac function, consequently significantly improving the survival rates of rats under extreme hypoxia, and this strategy can be used for rapid hypoxic adaptation. Mechanistically, fasting reduces blood glucose and further suppresses tissue mTOR activity. On the one hand, fasting-induced mTOR inhibition reduces unnecessary ATP consumption and increases ATP reserves under acute hypoxia as a result of decreased protein synthesis and lipogenesis; on the other hand, fasting-induced mTOR inhibition improves mitochondrial oxygen utilization efficiency to ensure ATP production under acute hypoxia, which is due to the significant decrease in ROS generation induced by enhanced mitophagy. Our findings highlight the important role of mTOR in acute hypoxic adaptation, and targeted regulation of mTOR could be a new strategy to improve acute hypoxic tolerance in the body.

3.
Cancer Cell Int ; 21(1): 599, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34758833

RESUMO

BACKGROUND: The high potential for tumor recurrence and chemoresistance is a major challenge of clinical gastric cancer treatment. Increasing evidence suggests that the presence of tumor initiating cells (TICs) is the principal cause of tumor recurrence and chemoresistance. However, the underlying mechanism of TIC development remains controversial. METHODS: To identify novel molecular pathways in gastric cancer, we screened the genomic expression profile of 155 gastric cancer patients from the TCGA database. We then described an improved 3D collagen I gels and tested the effects of collagen on the TIC phenotype of gastric cells using colony formation assay, transwell assay, and nude mouse models. Additionally, cell apoptosis assay was performed to examine the cytotoxicity of 5-fluorine and paclitaxel on gastric cancer cells cultured in 3D collagen I gels. RESULTS: Elevated expression of type I collagen was observed in tumor tissues from high stage patients (stage T3-T4) when compared to the low stage group (n=10, stage T1-T2). Furthermore, tumor cells seeded in a low concentration of collagen gels acquired TIC-like phenotypes and revealed enhanced resistance to chemotherapeutic agents, which was dependent on an integrin ß1 (ITGB1)/Y-box Binding Protein 1 (YBX1)/Secreted Phosphoprotein 1 (SPP1)/NF-κB signaling pathway. Importantly, inhibition of ITGB1/NF-κB signaling efficiently reversed the chemoresistance induced by collagen and promoted anticancer effects in vivo. CONCLUSIONS: Our findings demonstrated that type I collagen promoted TIC-like phenotypes and chemoresistance through ITGB1/YBX1/SPP1/NF-κB pathway, which may provide novel insights into gastric cancer therapy.

4.
Cancer Lett ; 526: 112-130, 2021 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-34826547

RESUMO

The cytoskeleton and cell-matrix adhesions constitute a dynamic network that controls cellular behavior during development and cancer. The Focal Adhesion Kinase (FAK) is a central actor of these cell dynamics, promoting cell-matrix adhesion turnover and active membrane fluctuations. However, the initial steps leading to FAK activation and subsequent promotion of cell dynamics remain elusive. Here, we report that the serine/threonine kinase PKCθ participates in the initial steps of FAK activation. PKCθ, which is strongly expressed in aggressive human breast cancers, controls the dynamics of cell-matrix adhesions and active protrusions through direct FAK activation, thereby promoting cell invasion and lung metastases. Using various tools for in vitro and live cell studies, we precisely decipher the molecular mechanisms of FAK activation. PKCθ directly interacts with the FAK FERM domain to open FAK conformation through PKCθ's specific V3 domain, while phosphorylating FAK at newly identified serine/threonine residues within nascent adhesions, inducing cell dynamics and aggressive behavior. This study thus places PKCθ-directed FAK opening and phosphorylations as an original mechanism controlling dynamic, migratory, and invasive abilities of aggressive breast cancer cells, further strengthening the emerging oncogenic function of PKCθ.

5.
Front Aging Neurosci ; 13: 754956, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34720999

RESUMO

Mutations in leucine-rich repeat kinase 2 gene (LRRK2) are the most frequent genetic factors contributing to Parkinson's disease (PD). G2385R-LRRK2 increases the risk for PD susceptibility in the Chinese population. However, the pathological role of G2385R-LRRK2 is not clear. In this study, we investigate the roles of G2385R-LRRK2 in neurodegeneration underlying PD pathogenesis using cell biology and pharmacology approaches. We demonstrated that expression of G2385R-LRRK2-induced neurotoxicity in human neuroblastoma SH-SY5Y and mouse primary neurons. G2385R-LRRK2 increased mitochondrial ROS, activates caspase-3/7, and increased PARP cleavage, resulting in neurotoxicity. Treatment with curcumin (an antioxidant) significantly protected against G2385R-LRRK2-induced neurodegeneration by reducing mitochondrial ROS, caspase-3/7 activation, and PARP cleavage. We also found that the cellular environmental stressor, H2O2 significantly promotes both WT-LRRK2- and G2385R-LRRK2-induced neurotoxicity by increasing mitochondrial ROS, caspase-3/7 activation, and PARP cleavage, while curcumin attenuated this combined neurotoxicity. These findings not only provide a novel understanding of G2385R roles in neurodegeneration and environment interaction but also provide a pharmacological approach for intervention for G2385R-LRRK2-linked PD.

6.
Cell Metab ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34784501

RESUMO

Apoptotic cell clearance by macrophages (efferocytosis) promotes resolution signaling pathways, which can be triggered by molecules derived from the phagolysosomal degradation of apoptotic cells. We show here that nucleotides derived from the hydrolysis of apoptotic cell DNA by phagolysosomal DNase2a activate a DNA-PKcs-mTORC2/Rictor pathway that increases Myc to promote non-inflammatory macrophage proliferation. Efferocytosis-induced proliferation expands the pool of resolving macrophages in vitro and in mice, including zymosan-induced peritonitis, dexamethasone-induced thymocyte apoptosis, and atherosclerosis regression. In the dexamethasone-thymus model, hematopoietic Rictor deletion blocked efferocytosing macrophage proliferation, apoptotic cell clearance, and tissue resolution. In atherosclerosis regression, silencing macrophage Rictor or DNase2a blocked efferocyte proliferation, apoptotic cell clearance, and plaque stabilization. In view of previous work showing that other types of apoptotic cell cargo can promote resolution in individual efferocytosing macrophages, the findings here suggest that signaling-triggered apoptotic cell-derived nucleotides can amplify this benefit by increasing the number of these macrophages.

7.
Biochimie ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34838647

RESUMO

AMPK is an important kinase regulating energy homeostasis and also a key protein involved in a variety of signal transduction pathways. It plays a vitally regulatory role in cellular senescence. Activation of AMPK can delay or block the aging process, which is of great significance in the treatment of cardiovascular diseases and other aging related diseases, and provides a potential target for new indications such as Alzheimer's disease. Therefore, AMPK signaling pathway plays an important role in aging research. The in-depth study of AMPK activators will provide more new directions for the treatment of age-related maladies and the development of innovative drugs. Autophagy is a process that engulfs and degrades own cytoplasm or organelles. Thereby, meeting the metabolic demands and updating certain organelles of the cell has become a hotspot in the field of anti-aging in recent years. AMPK plays an important role between autophagy and senescence. In our review, the relationship among AMPK signaling, autophagy and aging will be clarified through the interaction between AMPK and mTOR, ULK1, FOXO, p53, SIRT1, and NF -κB.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34630606

RESUMO

Carbapenemase-resistant Klebsiella pneumoniae (CR-KP) has become one of the nosocomial infections that seriously threaten the lives of patients, greatly increasing the burden on patients. In order to explore the resistance mechanism of clinically isolated CR-KP to carbapenems and perform multilocus sequence typing (MLST), to study the clinical characteristics of patients with different ST types of infection, we collected 74 CR-KP strains clinically isolated from the main 6 hospitals in Zhejiang province from January 2018 to July 2020. The sensitivity of the tested strains to 23 antibacterial drugs was determined by the microbroth dilution method, and PCR was applied. Gene amplification technology and DNA sequencing methods were used to detect the carbapenemase gene of the tested strains. Through the MLST of the tested strains, the clonal correlation and molecular epidemiological characteristics of the tested strains were explored, and the characteristics of CR-KP resistance, resistance mechanisms, and clinical characteristics of bacterial infections under different MLST types were analyzed at the same time. The results showed that 74 carbapenem-resistant Klebsiella pneumoniae strains showed high resistance to 21 commonly used antibacterial drugs, and all carbapenemase phenotypic screening tests were positive. MLST typing showed that 74 CR-KP strains had 17 ST typings, and ST11 was the dominant type (54.05%). The study also found that these ST11 strains are more likely to be resistant to carbapenem antibiotics. Most of them produce KPC carbapenemase, and a few are IMP, VIM, and NDM. Univariate analysis suggested that the proportion of patients in the ST11 group receiving treatment in ICU, the use rate of mechanical ventilation, and the proportion of drainage tube indwelling were higher than those in the non-ST11 group, and the survival rate of the ST11 group was lower than that of the non-ST11 group. Clinical data suggested that the same hospital was dominated by the same clonal epidemic in the same period. In view of the analysis of clinical data suggesting that patients who have received ICU treatment, mechanical ventilation, and drainage tube indwelling are prone to the risk of CR-KP strain (especially ST11) infection and low survival rate, such patients should arouse extensive clinical attention.

9.
Oncol Lett ; 22(5): 789, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34630702

RESUMO

Daidzein has been found to significantly inhibit the proliferation of lung cancer cells, while its potential molecular mechanisms remain unclear. To determine the molecular mechanism of daidzein on lung cancer cells, the Capital Bio Technology Human long non-coding (lnc) RNA Array v4, 4×180K chip was used to detect the gene expression profiles of 40,000 lncRNAs and 34,000 mRNAs in a human cancer cell line. Reverse transcription-quantitative (RT-q) PCR analysis was performed to detect the expression levels of target lncRNA and mRNAs in the H1299 cells treated with and without daidzein, using the lncRNA and mRNA gene chip. Bioinformatics analysis was performed to determine the differentially expressed genes from the results of the chip assays. There were 119 and 40 differentially expressed lncRNAs and mRNAs, respectively, that had a 2-fold change in expression level. A total of eight lncRNAs were upregulated in the H1299 lung cancer cells, while 111 lncRNAs were downregulated. Furthermore, five mRNAs were upregulated, and 35 mRNAs were downregulated. A total of six differentially expressed lncRNAs (ENST00000608897.1, ENST00000444196.1, ENST00000608741.1, XR_242163.1, ENST00000505196.1 and ENST00000498032.1) were randomly selected to validate the microarray data, which were consistent with the RT-qPCR analysis results. Differentially expressed mRNAs were enriched in important Gene Ontology terms and Kyoto Encyclopedia of Genes and Genomes pathways. Taken together, the results of the present study demonstrated that daidzein affected the expression level of lncRNAs in lung cancer cells, suggesting that daidzein may have potential effects on lung cancer cells.

10.
Front Chem ; 9: 760473, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631673

RESUMO

Lithium-ion capacitors (LICs) have been proposed as an emerging technological innovation that integrates the advantages of lithium-ion batteries and supercapacitors. However, the high-power output of LICs still suffers from intractable challenges due to the sluggish reaction kinetics of battery-type anodes. Herein, polypyrrole-coated nitrogen and phosphorus co-doped hollow carbon nanospheres (NPHCS@PPy) were synthesized by a facile method and employed as anode materials for LICs. The unique hybrid architecture composed of porous hollow carbon nanospheres and PPy coating layer can expedite the mass/charge transport and enhance the structural stability during repetitive lithiation/delithiation process. The N and P dual doping plays a significant role on expanding the carbon layer spacing, enhancing electrode wettability, and increasing active sites for pseudocapacitive reactions. Benefiting from these merits, the NPHCS@PPy composite exhibits excellent lithium-storage performances including high rate capability and good cycling stability. Furthermore, a novel LIC device based on the NPHCS@PPy anode and the nitrogen-doped porous carbon cathode delivers a high energy density of 149 Wh kg-1 and a high power density of 22,500 W kg-1 as well as decent cycling stability with a capacity retention rate of 92% after 7,500 cycles. This work offers an applicable and alternative way for the development of high-performance LICs.

11.
Signal Transduct Target Ther ; 6(1): 368, 2021 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-34645784

RESUMO

The long-term immunity and functional recovery after SARS-CoV-2 infection have implications in preventive measures and patient quality of life. Here we analyzed a prospective cohort of 121 recovered COVID-19 patients from Xiangyang, China at 1-year after diagnosis. Among them, chemiluminescence immunoassay-based screening showed 99% (95% CI, 98-100%) seroprevalence 10-12 months after infection, comparing to 0.8% (95% CI, 0.7-0.9%) in the general population. Total anti-receptor-binding domain (RBD) antibodies remained stable since discharge, while anti-RBD IgG and neutralization levels decreased over time. A predictive model estimates 17% (95% CI, 11-24%) and 87% (95% CI, 80-92%) participants were still 50% protected against detectable and severe re-infection of WT SARS-CoV-2, respectively, while neutralization levels against B.1.1.7 and B.1.351 variants were significantly reduced. All non-severe patients showed normal chest CT and 21% reported COVID-19-related symptoms. In contrast, 53% severe patients had abnormal chest CT, decreased pulmonary function or cardiac involvement and 79% were still symptomatic. Our findings suggest long-lasting immune protection after SARS-CoV-2 infection, while also highlight the risk of immune evasive variants and long-term consequences for COVID-19 survivors.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , Memória Imunológica , Modelos Imunológicos , SARS-CoV-2/imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , COVID-19/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia Computadorizada por Raios X
12.
Chem Rev ; 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34664951

RESUMO

In vivo imaging in the second near-infrared window (NIR-II, 1000-1700 nm), which enables us to look deeply into living subjects, is producing marvelous opportunities for biomedical research and clinical applications. Very recently, there has been an upsurge of interdisciplinary studies focusing on developing versatile types of inorganic/organic fluorophores that can be used for noninvasive NIR-IIa/IIb imaging (NIR-IIa, 1300-1400 nm; NIR-IIb, 1500-1700 nm) with near-zero tissue autofluorescence and deeper tissue penetration. This review provides an overview of the reports published to date on the design, properties, molecular imaging, and theranostics of inorganic/organic NIR-IIa/IIb fluorophores. First, we summarize the design concepts of the up-to-date functional NIR-IIa/IIb biomaterials, in the order of single-walled carbon nanotubes (SWCNTs), quantum dots (QDs), rare-earth-doped nanoparticles (RENPs), and organic fluorophores (OFs). Then, these novel imaging modalities and versatile biomedical applications brought by these superior fluorescent properties are reviewed. Finally, challenges and perspectives for future clinical translation, aiming at boosting the clinical application progress of NIR-IIa and NIR-IIb imaging technology are highlighted.

13.
Diabetol Metab Syndr ; 13(1): 106, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627359

RESUMO

BACKGROUND: Evidence suggests gut microbiome is associated with diabetes. However, it's unclear whether the association remains in non-diabetic participants. A Chinese monozygotic twin study, in which the participants are without diabetes, and are not taking any medications, was conducted to explore the potential association. METHODS: Nine pairs of adult monozygotic twins were enrolled and divided into two twin-pair groups (a and b). Clinical and laboratory measurements were conducted. Visceral adipose tissue (VAT) was assessed. Fecal samples were collected to analyze the microbiome composition by 16S rDNA gene amplicon sequencing. Liquid chromatography mass spectrometry was performed to detect the metabolites. RESULTS: The participants aged 53 years old averagely, with 8 (88.9%) pairs were women. All the participants were obese with VAT higher than 100 cm2 (152.2 ± 31.6). There was no significant difference of VAT between the twin groups (153.6 ± 30.4 cm2 vs. 150.8 ± 29.5 cm2, p = 0.54). Other clinical measurements, including BMI, lipid profiles, fasting insulin and blood glucose, were also not significantly different between groups (p ≥ 0.056), whereas HbA1c level of group a is significantly higher than group b (5.8 ± 0.3% vs. 5.6 ± 0.2%, p = 0.008). The number and richness of OTUs are relatively higher in group a, and 13 metabolites were significantly different between two groups. Furthermore, several of the 13 metabolites could be significantly linked to special taxons. The potential pathway involved drug metabolism-other enzymes, Tryptophan metabolism and Citrate cycle. CONCLUSIONS: Gut microbiome composition and their metabolites may modulate glucose metabolism in obese adults without diabetes, through Tryptophan metabolism, Citrate cycle and other pathways.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34617210

RESUMO

Insect feces are a new kind of biological organic fertilizer. Little is known about the influences of insect feces on rice growth and heavy metal migration from soil to rice plant. In this study, the effects of different amounts (CK (0%), T1 (2%), T2 (4%), T3 (6%), and T4 (8%)) of black soldier fly larvae (BSFL) feces on the rice growth and the migration/accumulation of heavy metals (Cd and Pb) were investigated by pot experiments within 2 years. The application of insect feces remarkably increased the contents of soil pH, organic matter, ammonium nitrogen, available phosphorus, and potassium. Meanwhile, the insect feces application reduced the weak acid-soluble contents of soil Cd and Pb by 8.3-56.8%, but increased those in the oxidizable (by 22.4-165.7%) and residual (by 1.8-225.6%) states. Except for the T4 treatment in the first year, all fertilization treatments increased the rice yield (up to 43.7% and 195.5% higher than those of CK within 2 years). Moreover, the insect feces application reduced the contents of Cd (8.3-66.7%) and Pb (6.4-61.8%) in different parts of rice. Under the same treatment, the metal contents in each part of rice in the second year were lower than those in the first year. The insect feces application decreased the absorption coefficients (24.4-57.5%) and secondary transport coefficients (3.6-44.1%) of Cd and Pb by rice plant. The findings implied that the insect feces might act as effective organic fertilizers for rice plants as well as reducing heavy metal accumulation in rice plants growing in polluted soil.

15.
Materials (Basel) ; 14(19)2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34640005

RESUMO

Ultrasonic-assisted electrolytic in-process dressing (UA-ELID) grinding is a promising technology that uses a metal-bonded diamond grinding wheel to achieve a mirror surface finish on hard and brittle materials. In this paper, the UA-ELID grinding was applied to nanocomposite ceramic for investigating the cavitation effect on the processing performance. Firstly, the ultrasonic cavitation theory was utilized to define the cavitation threshold, collapse of cavitation bubbles, and variation of their radii. Next, the online monitoring system was designed to observe the ultrasonic cavitation under different ultrasonic amplitude for the actual UA-ELID grinding test. A strong effect of ultrasonic cavitation on the grinding wheel surface and the formed oxide film was experimentally proved. Besides, under the action of ultrasonic vibration, the dressing effect of the grinding wheel was improved, and the sharpness of grain increased by 43.2%, and the grain distribution was dramatically changed with the increase of ultrasonic amplitude. Compared with the conventional ELID (C-ELID) grinding, the average protrusion height increased by 14.2%, while the average grain spacing dropped by 21.2%. The UA-ELID grinding reduced the workpiece surface roughness Rz and Ra by 54.2% and 46.5%, respectively, and increased the surface residual compressive stress by 44.5%. The surface morphology observation revealed a change in the material removal mechanism and improvement of the surface quality by ultrasonic cavitation effect. These findings are considered instrumental in theoretical and experimental substantiation of the optimal UA-ELID grinding parameters for the processing of nanocomposite ceramics.

16.
J Mater Chem B ; 9(42): 8793-8800, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34632477

RESUMO

The development of a rapid and intuitive method for the detection of a specific small molecule biomarker is important for understanding the pathogenesis of relevant diseases. Described here is the design and evaluation of an HClO-specific triggered self-immolative fluorescent sensor (RESClO) based on the structure of an N-protected Resorufin dye. Due to the interrupted π-conjugated structure of the Resorufin dye, the free sensor showed very weak absorption and fluorescence. It can quickly complete the response to HClO (within 10 s) with high selectivity and sensitivity (LOD = 16.8 nM) in aqueous solution. The sensor can be made into test strips to quickly detect HClO in the environment by obvious changes in color and fluorescence. It was successfully used for bioimaging of exogenous and endogenous HClO in cells and zebra fish. More importantly, it can also be used for visual imaging of mouse arthritis models. Thus, sensor RESClO can provide a simple and promising visual analytical tool for the detection of HClO in the environment and the early diagnosis of HClO-mediated related diseases.

17.
PLoS One ; 16(10): e0258194, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34597331

RESUMO

To identify long non-coding RNAs (lncRNAs) and their potential roles in hepatic fibrosis in rat liver issues induced by CCl4, lncRNAs and genes were analyzed in fibrotic rat liver tissues by RNA sequencing and verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR). Differentially expressed (DE) lncRNAs (DE-lncRNAs) and genes were subjected to bioinformatics analysis and used to construct a co-expression network. We identified 10 novel DE-lncRNAs that were downregulated during the hepatic fibrosis process. The cis target gene of DE-lncRNA, XLOC118358, was Met, and the cis target gene of the other nine DE-lncRNAs, XLOC004600, XLOC004605, XLOC004610, XLOC004611, XLOC004568, XLOC004580 XLOC004598, XLOC004601, and XLOC004602 was Nox4. The results of construction of a pathway-DEG co-expression network show that lncRNA-Met and lncRNAs-Nox4 were involved in oxidation-reduction processes and PI3K/Akt signaling pathway. Our results identified 10 DE-lncRNAs related to hepatic fibrosis, and the potential roles of DE-lncRNAs and target genes in hepatic fibrosis might provide new therapeutic strategies for hepatic fibrosis.


Assuntos
Doenças Genéticas Inatas/genética , Cirrose Hepática/genética , Fígado/metabolismo , RNA Longo não Codificante/genética , Transcriptoma/genética , Animais , Tetracloreto de Carbono/toxicidade , Redes Reguladoras de Genes/genética , Doenças Genéticas Inatas/induzido quimicamente , Doenças Genéticas Inatas/patologia , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/patologia , RNA Longo não Codificante/classificação , RNA Longo não Codificante/isolamento & purificação , Ratos , Análise de Sequência de RNA , Transdução de Sinais/genética
18.
Sci China Life Sci ; 2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34542812

RESUMO

Decades have passed since the first discovery of H10-subtype avian influenza virus (AIV) in chickens in 1949, and it has been detected in many species including mammals such as minks, pigs, seals and humans. Cases of human infections with H10N8 viruses identified in China in 2013 have raised widespread attention. Two novel reassortant H10N3 viruses were isolated from chickens in December 2019 in eastern China during routine surveillance for AIVs. The internal genes of these viruses were derived from genotype S (G57) H9N2 and were consistent with H5N6, H7N9 and H10N8, which cause fatal infections in humans. Their viral pathogenicity and transmissibility were further studied in different animal models. The two H10N3 isolates had low pathogenicity in chickens and were transmitted between chickens via direct contact. These viruses were highly pathogenic in mice and could be transmitted between guinea pigs via direct contact and respiratory droplets. More importantly, these viruses can bind to both human-type SAα-2,6-Gal receptors and avian-type SAα-2,3-Gal receptors. Asymptomatic shedding in chickens and good adaptability to mammals of these H10N3 isolates would make it easier to transmit to humans and pose a threat to public health.

19.
J Virol ; : JVI0088921, 2021 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-34495699

RESUMO

Porcine epidemic diarrhea virus (PEDV) causes a porcine disease associated with swine epidemic diarrhea. Different antagonistic strategies have been identified, and the mechanism by which PEDV infection impairs the production of interferon (IFN) and delays the activation of the IFN response to escape host innate immunity has been determined, but the pathogenic mechanisms of PEDV infection remain enigmatic. Our preliminary results revealed that endogenous F-box and WD repeat domain-containing 7 (FBXW7), the substrate recognition component of the SCF-type E3 ubiquitin ligase, is downregulated in PEDV-infected Vero E6 cells, according to the results from an isobaric tags for relative and absolute quantification (iTRAQ) analysis. Overexpression of FBXW7 in target cells makes them more resistant to PEDV infection, whereas ablation of FBXW7 expression by small interfering RNA (siRNA) significantly promotes PEDV infection. In addition, FBXW7 was verified as an innate antiviral factor capable of enhancing the expression of RIG-I and TBK1, and it was found to induce interferon-stimulated genes (ISGs), which led to an elevated antiviral state of the host cells. Moreover, we revealed that PEDV nonstructural protein 2 (nsp2) interacts with FBXW7 and targets FBXW7 for degradation through the K48-linked ubiquitin-proteasome pathway. Consistent with the results proven in vitro, FBXW7 reduction was also confirmed in different intestinal tissues from PEDV-infected specific-pathogen-free (SPF) pigs. Taken together, the data indicated that PEDV has evolved with a distinct antagonistic strategy to circumvent the host antiviral response by targeting the ubiquitin-proteasome-mediated degradation of FBXW7. Our findings provide novel insights into PEDV infection and pathogenesis. IMPORTANCE To counteract the host antiviral defenses, most viruses, including coronaviruses, have evolved with diverse strategies to dampen host IFN-mediated antiviral response, wither by interfering with or evading specific host regulators at multiple steps of this response. In this study, a novel antagonistic strategy was revealed showing that PEDV infection could circumvent the host innate response by targeted degradation of endogenous FBXW7 in target cells, a process that was verified to be a positive modulator for the host innate immune system. Degradation of FBXW7 hampers host innate antiviral activation and facilitates PEDV replication. Our findings reveal a new mechanism exploited by PEDV to suppress the host antiviral response.

20.
BMC Cancer ; 21(1): 1001, 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493238

RESUMO

BACKGROUND: The copper metabolism MURR1 domain (COMMD) protein family involved in tumor development and progression in several types of human cancer, but little is known about the function of COMMD proteins in hepatocellular carcinoma (HCC). METHODS: The ONCOMINE and the UALCAN databases were used to evaluate the expression of COMMD1-10 in HCC and the association of this family with individual cancer stage and tumor grade. Kaplan-Meier (K-M) Plotter and Cox analysis hint the prognostic value of COMMDs. A network comprising 50 most similar genes and COMMD1-10 was constructed with the STRING database. Gene set enrichment analysis (GSEA) was performed using LinkedOmics database. The correlations between COMMD expression and the presence of immune infiltrating cells were also analyzed by the tumor immune estimation resource (TIMER) database. GSE14520 dataset and 80 HCC patients were used to validated the expression and survival value of COMMD3. Human HCC cell lines were also used for validating the function of COMMD3. RESULTS: The expression of all COMMD family members showed higher expression in HCC tissues than that in normal tissues, and is associated with clinical cancer stage and pathological tumor grade. In HCC patients, the transcriptional levels of COMMD1/4 are positively correlated with overall survival (OS), while those of COMMD2/3/7/8/9 are negatively correlated with OS. Multivariate analysis indicated that a high level of COMMD3 mRNA is an independent prognostic factor for shorter OS in HCC patients. However, the subset of patients with grade 3 HCC, K-M survival curves revealed that high COMMD3/5/7/8/9 expression and low COMMD4/10 expression were associated with shorter OS. In addition, the expression of COMMD2/3/10 was associated with tumor-induced immune response activation and immune infiltration in HCC. The expression of COMMD3 from GSE14520 dataset and 80 patients are both higher in tumor than that in normal tissue, and a higher level of COMMD3 mRNA is associated with shorter OS. Knockdown of COMMD3 inhibits human HCC cell lines proliferation in vitro. CONCLUSIONS: Our study indicates that COMMD3 is an independent prognostic biomarker for the survival of HCC patients. COMMD3 supports the proliferation of HCC cells and contributes to the poor OS in HCC patients.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Neoplasias Hepáticas/patologia , Linfócitos do Interstício Tumoral/imunologia , Proteínas Adaptadoras de Transdução de Sinal/genética , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Carcinoma Hepatocelular/metabolismo , Feminino , Seguimentos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Neoplasias Hepáticas/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas
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