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2.
Front Immunol ; 15: 1339510, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38449860

RESUMEN

African swine fever (ASF) caused by African swine fever virus (ASFV) is a highly mortal and hemorrhagic infectious disease in pigs. Previous studies have indicated that ASFV modulates interferon (IFN) production. In this study, we demonstrated that ASFV pA151R negatively regulated type I IFN production. Ectopic expression of pA151R dramatically inhibited K63-linked polyubiquitination and Ser172 phosphorylation of TANK-binding kinase 1 (TBK1). Mechanically, we demonstrated that E3 ligase TNF receptor-associated factor 6 (TRAF6) participated in the ubiquitination of TBK1 in cGAS-STING signaling pathway. We showed that pA151R interacted with TRAF6 and degraded it through apoptosis pathway, leading to the disruption of TBK1 and TRAF6 interaction. Moreover, we clarified that the amino acids H102, C109, C132, and C135 in pA151R were crucial for pA151R to inhibit type I interferon production. In addition, we verified that overexpression of pA151R facilitated DNA virus Herpes simplex virus 1 (HSV-1) replication by inhibiting IFN-ß production. Importantly, knockdown of pA151R inhibited ASFV replication and enhanced IFN-ß production in porcine alveolar macrophages (PAMs). Our findings will help understand how ASFV escapes host antiviral immune responses and develop effective ASFV vaccines.


Asunto(s)
Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Animales , Porcinos , Ubiquitina-Proteína Ligasas , Factor 6 Asociado a Receptor de TNF , Ubiquitinación
3.
Autoimmunity ; 57(1): 2319204, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38409788

RESUMEN

Background: Lupus Nephritis (LN) is the primary causation of kidney injury in systemic lupus erythematosus (SLE). Ferroptosis is a programmed cell death. Therefore, understanding the crosstalk between LN and ferroptosis is still a significant challenge. Methods: We obtained the expression profile of LN kidney biopsy samples from the Gene Expression Omnibus database and utilised the R-project software to identify differentially expressed genes (DEGs). Then, we conducted a functional correlation analysis. Ferroptosis-related genes (FRGs) and differentially expressed genes (DEGs) crossover to select FRGs with LN. Afterwards, we used CIBERSORT to assess the infiltration of immune cells in both LN tissues and healthy control samples. Finally, we performed immunohistochemistry on LN human renal tissue. Results: 10619 DEGs screened from the LN biopsy tissue were identified. 22 hub-ferroptosis-related genes with LN (FRGs-LN) were screened out. The CIBERSORT findings revealed that there were significant statistical differences in immune cells between healthy control samples and LN tissues. Immunohistochemistry further demonstrated a significant difference in HRAS, TFRC, ATM, and SRC expression in renal tissue between normal and control groups. Conclusion: We developed a signature that allowed us to identify 22 new biomarkers associated with FRGs-LN. These findings suggest new insights into the pathology and therapeutic potential of LN ferroptosis inhibitors and iron chelators.


Asunto(s)
Ferroptosis , Lupus Eritematoso Sistémico , Nefritis Lúpica , Humanos , Nefritis Lúpica/genética , Ferroptosis/genética , Apoptosis , Biopsia
4.
Adv Ther ; 41(3): 967-990, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38286960

RESUMEN

Liver diseases cause a significant burden on public health worldwide. In spite of great advances during recent years, there are still many challenges in the diagnosis and treatment of liver diseases. During recent years, artificial intelligence (AI) has been widely used for the diagnosis, risk stratification, and prognostic prediction of various diseases based on clinical datasets and medical images. Accumulative studies have shown its performance for diagnosing patients with nonalcoholic fatty liver disease and liver fibrosis and assessing their severity, and for predicting treatment response and recurrence of hepatocellular carcinoma, outcomes of liver transplantation recipients, and risk of drug-induced liver injury. Herein, we aim to comprehensively summarize the current evidence regarding diagnostic, prognostic, and/or therapeutic role of AI in these common liver diseases.


Asunto(s)
Carcinoma Hepatocelular , Neoplasias Hepáticas , Enfermedad del Hígado Graso no Alcohólico , Humanos , Inteligencia Artificial , Cirrosis Hepática/complicaciones , Cirrosis Hepática/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/complicaciones , Enfermedad del Hígado Graso no Alcohólico/diagnóstico , Enfermedad del Hígado Graso no Alcohólico/terapia , Neoplasias Hepáticas/diagnóstico
5.
Front Nutr ; 10: 1275199, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37781120

RESUMEN

Aging is a universal and irreversible process, and the skin is an important feature that reflects the aging of the organism. Skin aging has been a focus of attention in recent years because it leads to changes in an individual's external features and the loss of many important biological functions. This experiment investigated the improvement effect of black tea extract (BTE) on the skin of aging mice under D-galactose induction. After 6 weeks of administration, the changes in skin bio-chemical indices and tissue structure were compared with the blank and positive control groups. It was observed that BTE increased water and hyaluronic acid (HA) content, decreased malondialdehyde (MDA) content, enhanced superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities in the skin of aging mice, and improved the structure of aging damaged skin tissues and increased the content of total collagen. The experimental results showed that BTE can play a significant anti-aging effect on the skin, which can be used as a functional food for aging inhibition.

6.
Adv Ther ; 2023 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-37801231

RESUMEN

INTRODUCTION: Bowel wall thickening is commonly observed in liver cirrhosis, but few studies have explored its impact on the long-term outcomes of patients with cirrhosis. METHODS: Overall, 118 patients with decompensated cirrhosis were retrospectively enrolled, in whom maximum wall thickness of small bowel, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum could be measured in computed tomography (CT) images. X-tile software was employed to determine the best cut-off values of each segment of bowel wall thickness for predicting the risk of further decompensation and death. Cumulative rates of further decompensation and death were calculated by Nelson-Aalen cumulative risk curve analyses. Predictors of further decompensation and death were evaluated by competing risk analyses. Sub-distribution hazard ratios (sHRs) were calculated. RESULTS: Cumulative rates of further decompensation were significantly higher in patients with wall thickness of ascending colon ≥ 11.7 mm (P = 0.014), transverse colon ≥ 3.2 mm (P = 0.043), descending colon ≥ 9.8 mm (P = 0.035), and rectum ≥ 7.2 mm (P = 0.045), but not those with wall thickness of small bowel ≥ 8.5 mm (P = 0.312) or sigmoid colon ≥ 7.1 mm (P = 0.237). Wall thickness of ascending colon ≥ 11.7 mm (sHR = 1.70, P = 0.030), transverse colon ≥ 3.2 mm (sHR = 2.15, P = 0.038), descending colon ≥ 9.8 mm (sHR = 1.43, P = 0.046), and rectum ≥ 7.2 mm (sHR = 2.38, P = 0.045) were independent predictors of further decompensation, but not wall thickness of small bowel ≥ 8.5 mm (sHR = 1.19, P = 0.490) or sigmoid colon ≥ 7.1 mm (sHR = 0.63, P = 0.076). Small bowel, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum wall thickness were not significantly associated with death. CONCLUSIONS: Colorectal wall thickening, but not small bowel wall, may be considered for the prediction of further decompensation in cirrhosis.

7.
Virol Sin ; 38(6): 911-921, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37659477

RESUMEN

African swine fever (ASF) is originally reported in East Africa as an acute hemorrhagic fever. African swine fever virus (ASFV) is a giant and complex DNA virus with icosahedral structure and encodes a variety of virulence factors to resist host innate immune response. S273R protein (pS273R), as a SUMO-1 specific cysteine protease, can affect viral packaging by cutting polymeric proteins. In this study, we found that pS273R was an important antagonistic viral factor that suppressed cGAS-STING-mediated type I interferon (IFN-I) production. A detailed analysis showed that pS273R inhibited IFN-I production by interacting with interferon regulatory factor 3 (IRF3). Subsequently, we showed that pS273R disrupted the association between TBK1 and IRF3, leading to the repressed IRF3 phosphorylation and dimerization. Deletion and point mutation analysis verified that pS273R impaired IFN-I production independent of its cysteine protease activity. These findings will help us further understand ASFV pathogenesis.


Asunto(s)
Virus de la Fiebre Porcina Africana , Fiebre Porcina Africana , Proteasas de Cisteína , Interferón Tipo I , Porcinos , Animales , Virus de la Fiebre Porcina Africana/genética , Proteínas Serina-Treonina Quinasas/genética , Factor 3 Regulador del Interferón , Interferón Tipo I/metabolismo , Proteasas de Cisteína/metabolismo
8.
Int J Biol Macromol ; 247: 125787, 2023 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-37437678

RESUMEN

Polysaccharides extracted from Dendrobium officinale have various physiological effects. In this study, we used D-galactose-induced senescent mice as an animal model to investigate the inhibitory effects of Dendrobium officinale polysaccharide (DOP) on oxidative damage in glial cells by attenuating oxidative stress and modulating the gut microbiota. The results showed that DOP significantly alleviated the activation of glial cells, increased the activity of antioxidant enzymes and reduced the MDA content in senescent mice. In addition, DOP reshaped the disordered gut microbiota, decreased the abundance ratio of Firmicutes to Bacteroidetes and increased the abundance of beneficial bacteria Lactobacillus. DOP may reverse the gut microbiota disturbance and alleviate the oxidative damage of glial cells, therefore exert potential neuroprotective effects by modulating gut microbiota.


Asunto(s)
Dendrobium , Microbioma Gastrointestinal , Ratones , Animales , Estrés Oxidativo , Polisacáridos/farmacología , Envejecimiento , Neuroglía
9.
Front Nutr ; 10: 1162110, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37153916

RESUMEN

Lead is a global pollutant that causes widespread concern. When a lead enters the body, it is distributed throughout the body and accumulates in the brain, bone, and soft tissues such as the kidney, liver, and spleen. Chelators used for lead poisoning therapy all have side effects to some extent and other drawbacks including high cost. Exploration and utilization of natural antidotes become necessary. To date, few substances originating from edible fungi that are capable of adsorbing lead have been reported. In this study, we found that two commonly eaten mushrooms Auricularia auricula and Pleurotus ostreatus exhibited lead adsorption capacity. A. auricula active substance (AAAS) and P. ostreatus active substance (POAS) were purified by hot-water extraction, ethanol precipitation from its fruiting bodies followed by ion exchange chromatography, ultrafiltration, and gel filtration chromatography, respectively. AAAS was 3.6 kDa, while POAS was 4.9 kDa. They were both constituted of polysaccharides and peptides. The peptide sequences obtained by liquid chromatography combined with tandem mass spectrometry (LC-MS/MS) proved that they were rich in amino acids with side chain groups such as hydroxyl, carboxyl, carbonyl, sulfhydryl, and amidogen. Two rat models were established, but only a chronic lead-induced poisoning model was employed to determine the detoxification of AAAS/POAS and their fruiting body powder. For rats receiving continuous lead treatment, either AAAS or POAS could reduce the lead levels in the blood. They also promoted the elimination of the burden of lead in the spleen and kidney. The fruiting bodies were also proved to have lead detoxification effects. This is the first study to identify new functions of A. auricula and P. ostreatus in reducing lead toxicity and to provide dietary strategies for the treatment of lead toxicity.

10.
Foods ; 12(9)2023 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-37174341

RESUMEN

Abscisic acid (ABA) plays a crucial role in regulating the ripening of non-climacteric strawberry fruit. In the present study, ABA was confirmed to promote strawberry ripening and induce the down-regulation of FaMADS1. The transient silence of FaMADS1 in strawberries promoted fruit ripening and induced the content of anthocyanin and soluble pectin but reduced firmness and protopectin through a tobacco rattle virus-induced gene silencing technique. In parallel with the accelerated ripening, the genes were significantly induced in the transiently modified fruit, including anthocyanin-related PAL6, C4H, 4CL, DFR, and UFGT, softening-related PL and XTH, and aroma-related QR and AAT2. In addition, the interaction between FaMADS1 and ABA-related transcription factors was researched. Yeast one-hybrid analysis indicated that the FaMADS1 promoter could interact with FaABI5-5, FaTRAB1, and FaABI5. Furthermore, dual-luciferase assay suggested that FaTRAB1 could actively bind with the FaMADS1 promoter, resulting in the decreased expression of FaMADS1. In brief, these results suggest that the ABA-dependent ripening of strawberry fruit was probably inhibited through inhibiting FaMADS1 expression by the active binding of transcript FaTRAB1 with the FaMADS1 promoter.

11.
Front Immunol ; 14: 1186916, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37228597

RESUMEN

Cyclic GMP-AMP synthase (cGAS) recognizes viral DNA and synthesizes cyclic GMP-AMP (cGAMP), which activates stimulator of interferon genes (STING/MITA) and downstream mediators to elicit an innate immune response. African swine fever virus (ASFV) proteins can antagonize host immune responses to promote its infection. Here, we identified ASFV protein QP383R as an inhibitor of cGAS. Specifically, we found that overexpression of QP383R suppressed type I interferons (IFNs) activation stimulated by dsDNA and cGAS/STING, resulting in decreased transcription of IFNß and downstream proinflammatory cytokines. In addition, we showed that QP383R interacted directly with cGAS and promoted cGAS palmitoylation. Moreover, we demonstrated that QP383R suppressed DNA binding and cGAS dimerization, thus inhibiting cGAS enzymatic functions and reducing cGAMP production. Finally, the truncation mutation analysis indicated that the 284-383aa of QP383R inhibited IFNß production. Considering these results collectively, we conclude that QP383R can antagonize host innate immune response to ASFV by targeting the core component cGAS in cGAS-STING signaling pathways, an important viral strategy to evade this innate immune sensor.


Asunto(s)
Virus de la Fiebre Porcina Africana , Interferón Tipo I , Animales , Virus de la Fiebre Porcina Africana/genética , ADN Viral/genética , Interferón Tipo I/metabolismo , Lipoilación , Nucleotidiltransferasas/genética , Nucleotidiltransferasas/metabolismo , Porcinos , Proteínas Virales/metabolismo
12.
Int J Biol Macromol ; 240: 124440, 2023 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-37062382

RESUMEN

Dendrobium officinale has anti-inflammatory effects and is one of the well-known functional foods. Dendrobium officinale polysaccharide (DOP) can reduce intestinal barrier disruption and excessive inflammatory response by regulating intestinal bacterial homeostasis as well as short-chain fatty acid levels. It can also inhibit the activation of astrocytes and microglia, further realizing the protective effect on neuronal apoptosis and apoptosis, thus exerting a significant alleviating effect on neurological diseases. There is now evidence that bidirectional communication between the central nervous system and the gastrointestinal tract may influence human neurology, cognition and behavior via the gut-brain axis. In this review, we review the structural characterization, bioactivity and possible bioactive mechanisms of DOP, so as to elucidate the advantages of DOP's action on CNS diseases, with the aim of providing new perspectives for its drug and functional food development as well as clinical applications.


Asunto(s)
Enfermedades del Sistema Nervioso Central , Dendrobium , Microbioma Gastrointestinal , Humanos , Dendrobium/química , Polisacáridos/farmacología , Polisacáridos/uso terapéutico , Polisacáridos/química , Antioxidantes/farmacología , Enfermedades del Sistema Nervioso Central/tratamiento farmacológico
13.
Dig Liver Dis ; 55(12): 1621-1631, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-36894390

RESUMEN

BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved the outcomes of cancer patients. However, ICIs often lead to colitis/diarrhea. This study aimed to assess the treatment of ICIs-associated colitis/diarrhea and outcomes. METHODS: PubMed, EMBASE, and Cochrane Library databases were searched for eligible studies which investigated the treatment and outcomes of colitis/diarrhea developing in patients who received ICIs. The pooled incidences of any-grade colitis/diarrhea, low-grade colitis, high-grade colitis, low-grade diarrhea, and high-grade diarrhea as well as the pooled rates of response to treatment, mortality, and ICIs permanent discontinuation and restarts in patients with ICIs-associated colitis/diarrhea were estimated using a random-effects model. RESULTS: Among the 11,492 papers initially identified, 27 studies were included. The pooled incidences of any-grade colitis/diarrhea, low-grade colitis, high-grade colitis, low-grade diarrhea, and high-grade diarrhea were 17%, 3%, 17%, 13%, and 15%, respectively. The pooled rates of overall response, response to corticosteroid therapy, and response to biological agents were 88%, 50%, and 96%, respectively. The pooled short-term mortality in patients with ICIs-associated colitis/diarrhea was 2%. The pooled incidences of ICIs permanent discontinuation and restarts were 43% and 33%, respectively. CONCLUSION: ICIs-associated colitis/diarrhea is common, but rarely lethal. Half of them are responsive to corticosteroid therapy. There is a fairly high rate of response to biological agents in steroid-refractory colitis/diarrhea patients.


Asunto(s)
Colitis , Inhibidores de Puntos de Control Inmunológico , Humanos , Colitis/inducido químicamente , Diarrea/inducido químicamente , Resultado del Tratamiento , Corticoesteroides
14.
Intern Emerg Med ; 18(4): 1203-1212, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36892797

RESUMEN

Pancreatic encephalopathy (PE) is a lethal complication of acute pancreatitis (AP), but its clinical characteristics and prognosis remain obscure. Herein, we performed a systematic review and meta-analysis to evaluate the incidence and outcomes of PE in AP patients. PubMed, EMBASE, and China National Knowledge Infrastructure were searched. Based on the data from cohort studies, the incidence and mortality of PE in AP patients were pooled. Based on the individual data from case reports, logistic regression analyses were performed to identify the risk factors for death in PE patients. Among 6702 papers initially identified, 148 were included. Based on 68 cohort studies, the pooled incidence and mortality of PE in AP patients were 11% and 43%, respectively. The causes of death were clearly reported in 282 patients, of which the most common was multiple organ failure (n = 197). Based on 80 case reports, 114 AP patients with PE were included. The causes of death were clearly reported in 19 patients, of which the most common was multiple organ failure (n = 8). Univariate analyses showed that multiple organ failure (OR = 5.946; p = 0.009) and chronic cholecystitis (OR = 5.400; p = 0.008) were the significant risk factors of death among patients with PE. PE is not a rare complication of AP and indicates poor prognosis. Such a high mortality of PE patients may be attributed to its coexistence of multiple organ failure.


Asunto(s)
Encefalopatías , Pancreatitis , Humanos , Pancreatitis/complicaciones , Pancreatitis/epidemiología , Enfermedad Aguda , Incidencia , Insuficiencia Multiorgánica , Encefalopatías/etiología
15.
Adv Ther ; 40(4): 1494-1529, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36697778

RESUMEN

INTRODUCTION: The role of human albumin (HA) infusion in cirrhotic patients has been increasingly recognized. This paper aims to summarize the evidence from meta-analyses regarding HA infusion for the management of cirrhosis and its complications. METHODS: A systematic search in the PubMed, EMBASE, and Cochrane library databases, and in reference lists was conducted. All relevant meta-analyses were identified and their findings were reviewed. The Assessment of Multiple Systematic Reviews 2 (AMSTAR-2) checklist was used to evaluate the methodological quality and the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system to assess the quality of evidence for significant outcomes. RESULTS: Among 300 papers initially identified, 18 meta-analyses have been included. Short- and long-term HA infusion at high doses decreased the mortality of patients with decompensated cirrhosis. In cirrhotic patients with ascites, long-term HA infusion reduced the recurrence of ascites, but not mortality. In cirrhotic patients undergoing large-volume paracentesis (LVP), HA infusion reduced the incidence of post-paracentesis circulatory dysfunction and hyponatremia, but not mortality or renal impairment. In cirrhotic patients with overt hepatic encephalopathy (HE), HA infusion improved the severity of overt HE, but not overall mortality. In cirrhotic patients with spontaneous bacterial peritonitis (SBP), but not those with non-SBP infections, HA infusion reduced the mortality and renal impairment. In cirrhotic patients with type-1 hepatorenal syndrome (HRS), an increment of 100 g in cumulative HA dose increased 1.15-fold survival, but not HRS reversal. In these meta-analyses, the quality of methodology was low or critically low, and that of the evidence was from very low to moderate. CONCLUSIONS: Based on the limited evidence from these meta-analyses, HA infusion appears to be beneficial in cirrhotic patients with ascites, overt HE, and SBP and in those undergoing LVP, but not in those with non-SBP infections.


Asunto(s)
Peritonitis , Albúmina Sérica Humana , Humanos , Ascitis/etiología , Ascitis/complicaciones , Cirrosis Hepática/complicaciones , Cirrosis Hepática/tratamiento farmacológico , Infusiones Intravenosas , Paracentesis/efectos adversos , Paracentesis/métodos , Peritonitis/complicaciones , Peritonitis/microbiología
16.
J Thromb Thrombolysis ; 55(1): 18-31, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-36402911

RESUMEN

Coronavirus disease 2019 (COVID-19) and COVID-19 vaccination may cause splanchnic vein thrombosis (SVT), which is potentially fatal. The present study aims to pool the incidence and outcomes of SVT patients with COVID-19 or having received COVID-19 vaccines. The PubMed, EMBASE, and Cochrane databases were searched. Based on the data from cohort studies, meta-analyses were performed to evaluate the incidence of SVT in COVID-19 patients or people having received COVID-19 vaccines. Pooled proportions were calculated. Based on the individual data from case reports, logistic regression analyses were performed to identify factors associated with death in SVT patients. Odds ratios (ORs) were calculated. Among 654 papers initially identified, 135 were included. Based on 12 cohort studies, the pooled incidence of SVT in COVID-19 patients was 0.6%. Data were insufficient to estimate the incidence of SVT after COVID-19 vaccination. Based on 123 case reports, the mortality was 14% (9/64) in SVT patients with COVID-19 and 25% (15/59) in those who received COVID-19 vaccines. Univariate analyses demonstrated that age (OR = 1.061; p = 0.017), diabetes mellitus (OR = 14.00; p = 0.002), anticoagulation (OR = 0.098; p = 0.004), and bowel resection (OR = 16.00; p = 0.001) were significantly associated with death in SVT patients with COVID-19; and anticoagulation (OR = 0.025; p = 0.003) and intravenous immunoglobulin (OR = 0.175; p = 0.046) were significantly associated with death in SVT patients who received COVID-19 vaccines. Multivariate analyses did not identify any independent factor for death in both patients. SVT in COVID-19 patients and in subjects who received COVID-19 vaccines carries a high mortality, but may be improved by anticoagulation. PROSPERO Identifier CRD42022315254.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Trombosis de la Vena , Humanos , Anticoagulantes/uso terapéutico , COVID-19/epidemiología , COVID-19/complicaciones , Prueba de COVID-19 , Vacunas contra la COVID-19/efectos adversos , Incidencia , Circulación Esplácnica , Trombosis de la Vena/epidemiología , Trombosis de la Vena/etiología , Trombosis de la Vena/diagnóstico
17.
Viruses ; 14(7)2022 07 07.
Artículo en Inglés | MEDLINE | ID: mdl-35891465

RESUMEN

Hosts exploit various approaches to defend against porcine reproductive and respiratory syndrome virus (PRRSV) infection. microRNAs (miRNAs) have emerged as key negative post-transcriptional regulators of gene expression and have been reported to play important roles in regulating virus infection. Here, we identified that miR-150 was differentially expressed in virus permissive and non-permissive cells. Subsequently, we demonstrated that PRRSV induced the expression of miR-150 via activating the protein kinase C (PKC)/c-Jun amino-terminal kinases (JNK)/c-Jun pathway, and overexpression of miR-150 suppressed PRRSV replication. Further analysis revealed that miR-150 not only directly targeted the PRRSV genome, but also facilitated type I IFN signaling. RNA immunoprecipitation assay demonstrated that miR-150 targeted the suppressor of cytokine signaling 1 (SOCS1), which is a negative regulator of Janus activated kinase (JAK)/signal transducer and activator of the transcription (STAT) signaling pathway. The inverse correlation between miR-150 and SOCS1 expression implies that miR-150 plays a role in regulating ISG expression. In conclusion, miR-150 expression is upregulated upon PRRSV infection. miR-150 feedback positively targets the PRRSV genome and promotes type I IFN signaling, which can be seen as a host defensive strategy.


Asunto(s)
MicroARNs , Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Animales , Línea Celular , Citocinas/genética , Citocinas/metabolismo , Genoma Viral , Quinasas Janus/metabolismo , MicroARNs/genética , MicroARNs/metabolismo , Síndrome Respiratorio y de la Reproducción Porcina/genética , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Virus del Síndrome Respiratorio y Reproductivo Porcino/metabolismo , Proteínas Supresoras de la Señalización de Citocinas/genética , Porcinos , Replicación Viral/fisiología
18.
ACS Omega ; 7(26): 22714-22724, 2022 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-35811864

RESUMEN

The flow and heat transfer characteristics of supercritical water within a triangular subchannel of a supercritical water-cooled reactor (SCWR) were numerically studied using the SSG turbulence model. The structural effect of staggered-blade-type grid spacers on the flow and heat transfer characteristics of supercritical water was analyzed. The results show that the wall temperatures calculated by the SSG model are consistent with the experimental data. The structure of the staggered-blade-type grid spacers has a significant effect on the supercritical heat transfer in the large specific heat region. The change in the inner-wall temperature and local heat transfer coefficient caused by the blocking rate at different leaf deflection angles has the same trend in the flow direction. The heat transfer coefficient peak gradually increases with an increase in deflection angle. A clear vortex is generated downstream of the grid spacer, and when the blade angle increases from 0 to 90°, the secondary flow is more obvious, and the velocity near the wall is the largest, which is about 1.99 times the center velocity. As the structure-blocking effect increases, the pressure drop in the subchannel gradually increases and the performance evaluation criteria first increase and then decrease. When using the staggered-blade-type grid spacer to improve the supercritical heat transfer effect, the spacing between adjacent grids should be ensured as far as possible, and avoid using it at the end of the channel.

19.
Int J Biol Macromol ; 217: 677-688, 2022 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-35853505

RESUMEN

Dendrobium officinale polysaccharide (DOP) has received an increasing amount of attention as it could alleviate AD-related cognitive impairment via the regulation of microglial activation. However, the modulatory mechanism of DOP on circadian rhythm disruption (CRD) and related cognitive impairment needs further investigation. In our study, the circadian rhythm disruption mice showed a deficit in recognition and spatial memory. DOP treatment reshaped the perturbation of gut microbiota caused by CRD, including up-regulated the abundance of Akkermansia and Alistipes, down-regulated the abundance of Clostridia. In addition, DOP restored histopathological changes, reduced inflammatory cells infiltration and strengthened mucosal integrity. Mechanistically, DOP ameliorated intestinal barrier dysfunction by up-regulating tight junction protein expression, which in turn improved the invasion of lipopolysaccharide to blood and brain. The change of these contributes to inhibiting the NF-κB activation and neuroinflammation, and thus attenuating hippocampus neuronal damage and the deposition of Aß. Meanwhile, our results revealed that DOP could reverse the levels of metabolites derived related to cognitive function improvement, and these metabolites were closely associated with the key microbiota. Therefore, we speculated that DOP has the potential to provide neuroprotection against cognitive impairment by modulating the gut microbiota.


Asunto(s)
Disfunción Cognitiva , Dendrobium , Microbioma Gastrointestinal , Animales , Ritmo Circadiano , Disfunción Cognitiva/tratamiento farmacológico , Modelos Animales de Enfermedad , Ratones , Extractos Vegetales/farmacología , Polisacáridos/metabolismo , Polisacáridos/farmacología , Polisacáridos/uso terapéutico
20.
Nutrients ; 14(11)2022 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-35684108

RESUMEN

Circadian rhythm disruption is detrimental and results in adverse health consequences. We used a multi-omics profiling approach to investigate the effects of Cyclocarya paliurus flavonoid (CPF)-enriched diets on gut microbiota, metabolites, and hypothalamus clock genes in mice with induced circadian rhythm disruption. It was observed that CPF supplementation altered the specific composition and function of gut microbiota and metabolites induced by circadian rhythm disruption. Analysis showed that the abundance of Akkermansia increased, while the abundance of Clostridiales and Ruminiclostridium displayed a significant downward trend after the CPF intervention. Correlation analysis also revealed that these gut microbes had certain correlations with the metabolites, suggesting that CPFs help the intestinal microbiota to repair the intestinal environment and modulate the release of some beneficial metabolites. Notably, single-cell RNA-seq revealed that CPF supplementation significantly regulated the expression of genes associated with circadian rhythm, myelination, and neurodegenerative diseases. Altogether, these findings highlight that CPFs may represent a promising dietary therapeutic strategy for treating circadian rhythm disruption.


Asunto(s)
Trastornos Cronobiológicos , Microbioma Gastrointestinal , Juglandaceae , Animales , Ritmo Circadiano , Modelos Animales de Enfermedad , Flavonoides/metabolismo , Flavonoides/farmacología , Hipotálamo , Juglandaceae/metabolismo , Ratones
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