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1.
J Exp Clin Cancer Res ; 42(1): 6, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36604718

RESUMO

BACKGROUND: Sorafenib resistance is a key impediment to successful treatment of patients with advanced hepatocellular carcinoma (HCC) and recent studies have reported reversal of drug resistance by targeting ferroptosis. The present study aimed to explore the association of fatty acid synthase (FASN) with sorafenib resistance via regulation of ferroptosis and provide a novel treatment strategy to overcome the sorafenib resistance of HCC patients. METHODS: Intracellular levels of lipid peroxides, glutathione, malondialdehyde, and Fe2+ were measured as indicators of ferroptosis status. Biological information analyses, immunofluorescence assays, western blot assays, and co-immunoprecipitation analyses were conducted to elucidate the functions of FASN in HCC. Both in vitro and in vivo studies were conducted to examine the antitumor effects of the combination of orlistat and sorafenib and CalcuSyn software was used to calculate the combination index. RESULTS: Solute carrier family 7 member 11 (SLC7A11) was found to play an important role in mediating sorafenib resistance. The up-regulation of FASN antagonize of SLC7A11-mediated ferroptosis and thereby promoted sorafenib resistance. Mechanistically, FASN enhanced sorafenib-induced ferroptosis resistance by binding to hypoxia-inducible factor 1-alpha (HIF1α), promoting HIF1α nuclear translocation, inhibiting ubiquitination and proteasomal degradation of HIF1α, and subsequently enhancing transcription of SLC7A11. Orlistat, an inhibitor of FASN, with sorafenib had significant synergistic antitumor effects and reversed sorafenib resistance both in vitro and in vivo. CONCLUSION: Targeting the FASN/HIF1α/SLC7A11 pathway resensitized HCC cells to sorafenib. The combination of orlistat and sorafenib had superior synergistic antitumor effects in sorafenib-resistant HCC cells.


Assuntos
Carcinoma Hepatocelular , Ferroptose , Neoplasias Hepáticas , Sorafenibe , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos , Ácido Graxo Sintases/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Orlistate/farmacologia , Orlistate/uso terapêutico , Sorafenibe/farmacologia , Sorafenibe/uso terapêutico
2.
Artigo em Inglês | MEDLINE | ID: mdl-36624239

RESUMO

OBJECTIVE: This study aims to investigate the association between the diurnal temperature range (DTR) and allergic rhinitis (AR) outpatient visits in Lanzhou, China, utilizing more than 7 years of participant surveys. METHODS: Our study used the distributed lag non-linear model (DLNM) aimed to evaluate the association between DTR and AR outpatient visits. We also performed subgroup analyses in order to find susceptible populations by gender and age groups. RESULTS: In 2013-2019, DTR in Lanzhou demonstrates a non-linear correlation with outpatient visits for AR, which is S-shaped. In addition, when DTR was located in the 0.9-5.3 °C and 12-20 °C compared with 12 °C, the risk of outpatient visits for AR increased. Moreover, males appeared to be more vulnerable to the DTR effect than females, the risk of children visits exceeded both the adult and the elderly groups at the higher DTR. CONCLUSION: Our study adds to the evidence that DTR is a possible risk factor for outpatient visits for AR; therefore, the public health sector and medical staff should take DTR into account when it comes to preventing AR onset.

3.
Angew Chem Int Ed Engl ; : e202218803, 2023 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-36596979

RESUMO

The use of non-solvating, or as-called sparingly-solvating, electrolytes (NSEs), is regarded as one of the most promising solutions to the obstacles to the practical applications of Li-S batteries. However, it remains a puzzle that long-life Li-S batteries have rarely, if not never, been reported with NSEs, despite their good compatibility with Li anode. Here, we find the capacity decay of Li-S batteries in NSEs is mainly due to the accumulation of the dead Li2 S at the cathode side, rather than the degradation of the anodes or electrolytes. Based on this understanding, we propose an electrochemical strategy to reactivate the accumulated Li2 S and revive the dead Li-S batteries in NSEs. With such a facile approach, Li-S batteries with significantly improved cycling stability and accelerated dynamics are achieved with diglyme-, acetonitrile- and 1,2-dimethoxyethane-based NSEs. Our finding may rebuild the confidence in exploiting non-solvating Li-S batteries with practical competitiveness.

4.
Front Genet ; 13: 1050192, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36452160

RESUMO

Pelteobagrus vachelli is a freshwater fish with high economic value, but the lack of genome resources has severely restricted its industrial development and population conservation. Here, we constructed the first chromosome-level genome assembly of P. vachelli with a total length of approximately 662.13 Mb and a contig N50 was 14.02 Mb, and scaffolds covering 99.79% of the assembly were anchored to 26 chromosomes. Combining the comparative genome results and transcriptome data under environmental stress (high temperature, hypoxia and Edwardsiella. ictaluri infection), the MAPK signaling pathway, PI3K-Akt signaling pathway and apelin signaling pathway play an important role in environmental adaptation of P. vachelli, and these pathways were interconnected by the ErbB family and involved in cell proliferation, differentiation and apoptosis. Population evolution analysis showed that artificial interventions have affected wild populations of P. vachelli. This study provides a useful genomic information for the genetic breeding of P. vachelli, as well as references for further studies on fish biology and evolution.

6.
Mikrochim Acta ; 190(1): 29, 2022 12 16.
Artigo em Inglês | MEDLINE | ID: mdl-36522482

RESUMO

Fluorescein-functionalized fluorescent polymer dots (F-PDs) were prepared by a facile one-pot method by magnetic stirring under mild conditions based on carboxymethylcellulose (CMC) and fluorescein as the precursors. The obtained F-PDs exhibited a nanoscale size of 3.2 ± 1.1 nm, excellent water solubility, and bright yellow fluorescence emission with a fluorescence quantum yield of 12.0%. The fluorescent probe displays rapid and sensitive chiral discrimination for lysine focused on different complexation abilities between lysine enantiomers and Cu2+. The concentration of L-lysine in the range 4 to 14 mM (R2 = 0.997) was measured by the fluorescence intensity ratio (I513/I429); the exitation wavelength was set to λex = 365 nm. The detection limit was 0.28 mM (3σ/slope). Importantly, this sensor accurately predicted the enantiomeric excess (ee) of lysine enantiomers at the designed concentration (lysine: 20 mM; Cu2+: 10 mM) ranges. The proposed sensor was successfully applied to determine L-lys (recovery: 95.8-101%; RSD: 0.465-3.34%) and ee values (recovery: 98.5-102%; RSD: 2.61-3.21%) in human urine samples using the standard addition method.


Assuntos
Pontos Quânticos , Humanos , Lisina , Polímeros , Fluoresceína , Corantes Fluorescentes
7.
Water Environ Res ; 94(12): e10817, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36524464

RESUMO

Sulfamethoxazole (SMX) is one of veterinary drugs and food additives, which has been frequently detected in surface waters in recent years and will cause damage to organisms. Therefore, SMX was selected as a target to be investigated, including the degradation kinetics, evolution of toxicity, and antibiotic resistance genes (ARGs) of SMX during chlorination in batch reactors and water distribution systems (WDS), to determine the optimal factors for removing SMX. In the range of investigated pH (6.3-9.0), the SMX degradation had the fastest rate at close to neutral pH. The chlorination of SMX was affected by the initial total free chlorine concentration, and the degradation of SMX was consistent with second-order kinetics. The rate constants in batch reactors are (2.23 ± 0.07) × 102 M-1  s-1 and (5.04 ± 0.30) × 10 M-1  s-1 for HClO and ClO-1 , respectively. Moreover, the rate constants in WDS are (1.76 ± 0.07) × 102 M-1  s-1 and (4.06 ± 0.62) × 10 M-1  s-1 , respectively. The degradation rate of SMX was also affected by pipe material, and the rate followed the following order: stainless-steel pipe (SS) > ductile iron pipe (DI) > polyethylene pipe (PE). The degradation rate of SMX in the DI increased with increasing flow rate, but the increase was limited. In addition, SMX could increase the toxicity of water initially, yet the toxicity reduced to the level of tap water after 2-h chlorination. And the relative abundance of ARGs (sul1 and sul2) of tap water samples was significantly increased under different chlorination conditions. PRACTITIONER POINTS: The degradation rate of SMX in batch reactor and WDS is different, and they could be described by first- or second-order kinetics. The degradation of SMX had the fastest rate at neutral pH. The degradation rate of SMX was also affected by pipe material and flow velocity. SMX increased the toxicity of water initially, yet the toxicity reduced after a 2-h chlorination. SMX increased the relative abundance of antibiotic resistance genes sul1 and sul2.


Assuntos
Sulfametoxazol , Poluentes Químicos da Água , Sulfametoxazol/toxicidade , Antibacterianos/química , Halogenação , Água , Resistência Microbiana a Medicamentos/genética , Cinética , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/química
8.
Mediators Inflamm ; 2022: 5676256, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36518880

RESUMO

Hepatic ischemia/reperfusion injury (HIRI) is a common complication of liver surgery requiring hepatic disconnection, such as hepatectomy and liver transplantation. The aim of this study was to investigate the effects of cordycepin on HIRI and to elucidate the underlying mechanisms. Balb/c mice were randomly divided into six groups: a normal control group, sham group, H-cordycepin group, HIRI group, L-cordycepin (25 mg/kg) + HIRI group, and H-cordycepin (50 mg/kg) + HIRI group. Mice were subjected to I/R, and cordycepin was intragastrically administered for seven consecutive days before surgery. Orbital blood and liver specimens were collected at 6 and 24 h after HIRI. Serum levels of ALT and AST were decreased in the cordycepin pretreatment groups. Notably, cordycepin attenuated the inflammatory response and the production of proapoptosis proteins, while increasing expression of antiapoptosis proteins and decreasing expression of autophagy-linked proteins. Furthermore, cordycepin inhibited activation of the MAPK/NF-κB signaling pathway. Collectively, these results indicate that cordycepin pretreatment ameliorated hepatocyte injury caused by HIRI. As compared with the HIRI group, cordycepin pretreatment mitigated the inflammatory response and inhibited apoptosis and autophagy via regulation of the MAPK/NF-κB signaling pathway.


Assuntos
NF-kappa B , Traumatismo por Reperfusão , Animais , Camundongos , Apoptose , Isquemia/metabolismo , Fígado/metabolismo , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo
9.
J Gastrointest Oncol ; 13(5): 2553-2564, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36388690

RESUMO

Background: Both N6-methyladenosine (m6A) ribonucleic acid (RNA) methylation and ferroptosis regulators are demonstrated to have significant effects on the malignant clinicopathological characteristics of pancreatic adenocarcinoma (PAAD) patients. However, the currently available clinical indexes are not sufficient to predict precise prognostic outcomes pf PAAD patients accurately. This study aims to examine the clinicopathologic features of m6A RNA methylation and ferroptosis regulators in predicting the outcomes of different types of cancer. Methods: As the foundation for this research, the differentially expressed genes (DEGs) between PAAD tissues and adjacent normal tissues were first identified. Next, dimensional reduction analysis (DCA) based on m6A RNA methylation regulators and ferroptosis regulators were performed and DEGs between good/poor prognosis PAAD patient clusters were identified. DEGs were then screened by Cox analysis, and finally a risk signature was established by least absolute shrinkage and selection operator (LASSO) analyses. The prediction model based on risk score was further evaluated by a validation set from Gene Expression Omnibus (GEO) database. Results: In total, 4 m6A RNA methylation regulator genes and 29 ferroptosis regulator genes were found to have close causal relationships with the prognosis of PAAD, and a risk score with 3 m6A methylation regulators (i.e., IGF2BP2, IGF2BP3, and METTL16) and 4 ferroptosis regulators (i.e., ENPP2, ATP6V1G2, ITGB4, and PROM2) was constructed and showed to be highly involved in PAAD progression and could serve as effective markers for prognosis with AUC value equaled 0.753 in training set and 0.803 in validation set. Conclusions: The combined prediction model, composed of seven regulators of m6A methylation and ferroptosis, in this study more effectively reflects the progression and prognosis of PAAD than previous single genome or epigenetic analysis. Our study provides a broader perspective for the subsequent establishment of prognostic models and the patients may benefit from more precision management.

10.
Mol Psychiatry ; 2022 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-36434057

RESUMO

Progressive grey matter loss has been demonstrated among clinical high-risk (CHR) individuals who convert to psychosis, but it is unknown whether these changes occur prior to psychosis onset. Identifying illness-related neurobiological mechanisms that occur prior to conversion is essential for targeted early intervention. Among participants in the third wave of the North American Prodrome Longitudinal Study (NAPLS3), this report investigated if steeper cortical thinning was observable prior to psychosis onset among CHR individuals who ultimately converted (CHR-C) and assessed the shortest possible time interval in which rates of cortical thinning differ between CHR-C, CHR non-converters (CHR-NC), and health controls (HC). 338 CHR-NC, 42 CHR-C, and 62 HC participants (age 19.3±4.2, 44.8% female, 52.5% racial/ethnic minority) completed up to 5 MRI scans across 8 months. Accelerated thinning among CHR-C compared to CHR-NC and HC was observed in multiple prefrontal, temporal, and parietal cortical regions. CHR-NC also exhibited accelerated cortical thinning compared to HC in several of these areas. Greater percent decrease in cortical thickness was observed among CHR-C compared to other groups across 2.9±1.8 months, on average, in several cortical areas. ROC analyses discriminating CHR-C from CHR-NC by percent thickness change in a left hemisphere region of interest, scanner, age, age2, and sex had an AUC of 0.74, with model predictive power driven primarily by percent thickness change. Findings indicate that accelerated cortical thinning precedes psychosis onset and differentiates CHR-C from CHR-NC and HC across short time intervals. Mechanisms underlying cortical thinning may provide novel treatment targets prior to psychosis onset.

11.
J Oncol ; 2022: 1774095, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36385965

RESUMO

Methods: First, the expression of LGR4 in HCC tumor tissues and cell lines was detected by western blotting and immunofluorescence. The ability of cell proliferation, migration, and invasion was detected with CCK8, wound-healing, and transwell assays when overexpressing LGR4 or treating with metformin. The ß-catenin expression was detected by immunofluorescence. In order to investigate novel AS-associated LGR4, we discarded LGR4 isoforms from GSO databases. We used siRNA to knock down the specific isoform to check the cell proliferation, migration, and invasion when treated with metformin. Results: The level of LGR4 expression was higher in HCC cell lines and tumor tissues. The HCC cell proliferation, migration, and invasion were increased when overexpressing LGR4, which could be reduced by metformin treatment. The GEO database (GSE190076) showed that LGR4 had switching properties in HCC cell lines treated with metformin. We used siRNA to knock down the specific isoform, and the result showed that the specific isoform siRNA could promote the inhibition of cell invasion caused by metformin treatment. Conclusions: LGR4 could promote the ability of cell proliferation, migration, and invasion in HCC, which could be reduced by metformin through alternative splicing.

12.
Artigo em Inglês | MEDLINE | ID: mdl-36387364

RESUMO

The formation of foam cells is a characteristic of the occurrence and development of atherosclerosis. ATP-binding cassette subfamily A1 and G1 (ABCA1 and ABCG1) and scavenger receptor B1 (SR-B1) play critical roles in promoting intracellular cholesterol efflux to high-density lipoprotein (HDL) or apolipoprotein A1 (apoA1). We attempted to test the effect of the tetramethylpyrazine-paeoniflorin pair (TP) on cholesterol outflow in foam cells derived from macrophages. In this study, RAW264.7 macrophages were treated with 80 mg/L oxidized low-density lipoprotein (ox-LDL) for 24 h to obtain foam cells. Then they were intervened with TP (tetramethylpyrazine 40 ug/ml plus paeoniflorin 80 ug/ml) for additional 24 h. The distribution of cholesterol in foam cells was evaluated by oil red O staining. The contents of total cholesterol (TC) and free cholesterol (FC) were assessed with commercial kits. Fluorescent imaging was observed with a fluorescent inverted microscope. The capacity of cholesterol efflux was measured with a fluorescent plate reader, and the transcript and protein levels of ABCA1, ABCG1, and SR-B1 were detected by Western blot and quantitative polymerase chain reactions (Q-PCRs). Cytokines in the medium were detected by ELISA and adjusted by total cellular proteins. The results showed that TP decreased ox-LDL-induced cholesterol deposition and foam cell formation by promoting cholesterol efflux to apoA1, which was related to the upregulation of ABCA1 and ABCG1. Moreover, TP decreased the secretion of ox-LDL-induced tumor necrosis factor alpha (TNF-α), interleukin 1 beta (IL-1ß), and monocyte chemotactic protein-1 (MCP-1), an important profoam cell cytokine in atherosclerosis.

13.
IEEE Trans Ultrason Ferroelectr Freq Control ; 69(12): 3224-3231, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36343006

RESUMO

Ultrasound neuromodulation is an emerging technology. A significant amount of effort has been devoted to investigating the feasibility of noninvasive ultrasound retinal stimulation. Recent studies have shown that ultrasound can activate neurons in healthy and degenerated retinas. Specifically, high-frequency ultrasound can evoke localized neuron responses and generate patterns in visual circuits. In this review, we recapitulate pilot studies on ultrasound retinal stimulation, compare it with other neuromodulation technologies, and discuss its advantages and limitations. An overview of the opportunities and challenges to develop a noninvasive retinal prosthesis using high-frequency ultrasound is also provided.


Assuntos
Retina , Próteses Visuais , Retina/diagnóstico por imagem , Retina/fisiologia , Ultrassonografia
14.
Pharmacol Res ; 185: 106483, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36252774

RESUMO

Allergic rhinitis (AR) is a series of reactions to allergen mediated by immunoglobulin E (IgE) and is one of the most common allergic diseases that affects children. Traditional Chinese Medicine, due to its diverse regulatory functions, may offer new strategies for AR therapy. Huanggui Tongqiao Granules (HTG) is a Chinese formula consisting of twelve herbs and has long been prescribed for patients with AR. The aim of this study is to determine the possible targets and action mechanisms of HTG for the AR treatment. SymMap database and TMNP algorithm were employed to show that interferon-gamma (IFN-gamma), acting as a molecular link between immunity and neural circuits, is the involved key target. The enrichment of immune and virus-related signaling pathways indicated the neuroimmunomodulatory potential of HTG. Then, AR mouse model was established by ovalbumin (OVA) challenge and was used to verify the therapeutic effects of HTG in vivo. HTG significantly relieved AR symptoms and nasal mucosal inflammation, reduced OVA-specific IgE levels and balanced IFN-gamma/IL-4 ratio. Moreover, transcriptional profile based on clinical data presented that blood cell-specific IFN-gamma co-expressed gene module (BIM) was underexpressed in AR patients, further validating the potential of IFN-gamma as target for AR. Collectively, these findings suggest that HTG could be a promising candidate drug for AR.


Assuntos
Mucosa Nasal , Rinite Alérgica , Camundongos , Animais , Mucosa Nasal/metabolismo , Camundongos Endogâmicos BALB C , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/metabolismo , Imunoglobulina E , Ovalbumina , Interferon gama/metabolismo , Modelos Animais de Doenças , Algoritmos , Citocinas/metabolismo
16.
Exp Dermatol ; 2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36164970

RESUMO

The etiology of systemic lupus erythematous (SLE) remains unclear. Pyroptosis, a new model of programmed cell death, was poorly explored in the pathogenesis of SLE. We found cell pyroptosis in CD4+T cells of SLE patients and kidneys from MRL/lpr mice by examining caspase-1 and gasdermin D (GSDMD) in by RT-PCR, Western blot, and levels of IL-1ß, IL-18 and TNF-α were detected by RT-PCR and Elisa. Expression of caspase-1 and GSDMD and levels of IL-1ß, IL-18, TNF-α decreased significantly after downregulation of hsa_circ_0012919 (p < 0.05). Inhibition of miR-125a-3p enhanced expression of caspase-1 and GSDMD (p < 0.05), and increased the release of IL-1ß, IL-18 and TNF-α (p < 0.05), thereby counteracting the effect of hsa_circ_0012919 knockdown on pyroptosis. Finally, we identified GSDMD as the target gene of miR-125a-3p. Silencing GSDMD reversed the effect of 5-aza-deoxycytidine in increasing release of IL-1ß, IL-18, TNF-α and activating caspase-1, but it could be reversed by miR-125a-3p inhibitor. In conclusion, hsa_circ_0012919 regulated the pyroptosis in the CD4+ T cells of SLE patients by miR-125a-3p/GSDMD axis.

17.
Front Psychol ; 13: 929045, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36081721

RESUMO

Previous studies of the relationship between hope and life satisfaction left the underlying mechanism of how hope predicts life satisfaction unexplored to scholars. This study thus investigates the two potential mediators in the relationship between hope and life satisfaction among a sample of Chinese shadow education institution (SEI) tutors who may be under immense professional development pressure from a cross-sectional approach. The main body of the study consists of an online survey in which 221 SEI tutors reported their hope, positive coping, perceived social support, and life satisfaction. The survey results were analyzed using mediation and moderation analysis via SPSS 23.0. The results indicated that positive coping improved the relationship between hope and life satisfaction, supporting the hypothesis regarding the serial mediating effect of positive coping and perceived social support. In other words, tutors with a high level of hope tend to adopt positive coping strategies, thus will receive more social support and improve life satisfaction. Our findings revealed the independent and accumulative mediating effects of positive coping and perceived social support on the relationship between hope and life satisfaction, and had implications for the psychological intervention of SEI tutors who are currently facing enormous industry pressure.

18.
Genet Res (Camb) ; 2022: 9582363, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36072011

RESUMO

Background: The human body has more than 600 kinds of skeletal muscles, which accounts for about 40% of the whole weight. Most skeletal muscles can make bones move, and their strength and endurance directly affect their performance during exercise. Methods: To determine the effects of exercise and time on human skeletal muscle, we downloaded the microarray expression profile of GSE1832 and analyzed it to select differentially expressed genes (DEGs). Then, a protein-protein interaction (PPI) network was established, and the hub genes were identified. Afterwards, DEGs were applied to perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Finally, with the help of Gene Set Enrichment Analysis (GSEA), the gene sets in the 7 samples were enriched in the KEGG pathway. Results: Through a series of bioinformatics analyses, we obtained a total of 271 DEGs. After that, four hub genes were determined through the PPI network, namely, EP300, STAT1, CDKN1A, and RAC2. In addition, we got that these DEGs were enriched in GO, such as regulation of cell population proliferation, cellular water homeostasis, and so on, and in KEGG, namely, hepatitis B, Epstein-Barr virus infection, small cell lung cancer, pathways in cancer, and others. Finally, the gene set in the samples obtained by GSEA was enriched in the cell cycle, chemokine signaling pathway, DNA replication, cytokine receptor interaction, ECM receptor interaction, and focal adhesion in KEGG. Conclusion: The findings obtained in this study will provide new clues for elucidating the mechanism of exercise and time on human skeletal muscles.


Assuntos
Biologia Computacional , Infecções por Vírus Epstein-Barr , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Herpesvirus Humano 4 , Humanos , Músculo Esquelético
19.
Int J Mol Sci ; 23(17)2022 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-36077519

RESUMO

Yellow catfish (Pelteobagrus fulvidraco) is an important aquaculture fish susceptible to Aeromonas veronii infection, which causes acute death resulting in huge economic losses. Understanding the molecular processes of host immune defense is indispensable to disease control. Here, we conducted the integrated and comparative analyses of the transcriptome and metabolome of yellow catfish in response to A. veronii infection at the invaded stage and recovering stage. The crosstalk between A. veronii-induced genes and metabolites uncovered the key biomarkers and pathways that strongest contribute to different response strategies used by yellow catfish at corresponding defense stages. We found that at the A. veronii invading stage, the immune defense was strengthened by synthesizing lipids with energy consumption to repair the skin defense line and accumulate lipid droplets promoting intracellular defense line; triggering an inflammatory response by elevating cytokine IL-6, IL-10 and IL-1ß following PAMP-elicited mitochondrial signaling, which was enhanced by ROS produced by impaired mitochondria; and activating apoptosis by up-regulating caspase 3, 7 and 8 and Prostaglandin F1α, meanwhile down-regulating FoxO3 and BCL6. Apoptosis was further potentiated via oxidative stress caused by mitochondrial dysfunction and exceeding inflammatory response. Additionally, cell cycle arrest was observed. At the fish recovering stage, survival strategies including sugar catabolism with D-mannose decreasing; energy generation through the TCA cycle and Oxidative phosphorylation pathways; antioxidant protection by enhancing Glutathione (oxidized), Anserine, and α-ketoglutarate; cell proliferation by inducing Cyclin G2 and CDKN1B; and autophagy initiated by FoxO3, ATG8 and ATP6V1A were highlighted. This study provides a comprehensive picture of yellow catfish coping with A. veronii infection, which adds new insights for deciphering molecular mechanisms underlying fish immunity and developing stage-specific disease control techniques in aquaculture.


Assuntos
Peixes-Gato , Doenças dos Peixes , Aeromonas veronii/genética , Animais , Peixes-Gato/metabolismo , Doenças dos Peixes/genética , Proteínas de Peixes/genética , Metaboloma , Transcriptoma
20.
PPAR Res ; 2022: 8161946, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35966821

RESUMO

Hepatic ischemia-reperfusion (IR) injury is a clinically significant process that frequently occurs in liver transplantation, partial hepatectomy, and hemorrhagic shock. The aim of this study was to explore the effectiveness of luteolin in hepatic IR injury and the underlying mechanism. BALB/c mice were randomly divided into six groups, including normal controls (NC), luteolin (50 mg/kg), sham procedure, IR+25 mg/kg luteolin, and IR+50 mg/kg luteolin group. Serum and tissue samples were collected at 6 and 24 h after reperfusion to assay liver enzymes, inflammatory factors, expression of proteins associated with apoptosis and autophagy, and factors associated with the extracellular signal-regulated kinase/peroxisome proliferator-activated receptor alpha (ERK/PPARα) pathway. Luteolin preconditioning decreased hepatocyte injury caused by ischemia-reperfusion, downregulated inflammatory factors, and inhibited apoptosis and autophagy. Luteolin also inhibited ERK phosphorylation and activated PPARα.

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