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1.
J Fish Dis ; 47(3): e13896, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38054569

RESUMEN

Nocardia seriolae is the primary aetiological agent of nocardiosis in fish, which causes mass mortality in freshwater and marine fish. ß-ketoacyl-ACP synthase (KAS) is one of the essential enzymes in the synthesis of mycolic acids (MASs) in Mycobacterium spp. and has been chosen as the target for therapeutic intervention in mycobacterial diseases. In the present study, a kasB homologue gene (kasB) was identified in the genome of N. seriolae, and the gene-deficient mutant (ΔkasB) was generated based on a clinical isolate, XSYC-Ns. Compared to the wild-type (WT) strain, the ΔkasB showed a measurably growth defect in vitro but retained the acid-fastness in acid-fast staining. Observation of the cell ultrastructure showed some alterations in the cell wall of the ΔkasB strain. Compared to its original strain, the cell wall lipid layer seemed sparser, and a wider electron-transparent zone was observed in the cell wall of ΔkasB strain. Moreover, the ΔkasB strain showed impaired ability of cell invasion as well as intracellular survival in the cell line originating from the head-kidney of the large yellow croaker (LYC-hK), compared to its original strain. In addition, the deficiency of ΔkasB significantly attenuated the virulence of N. seriolae in largemouth bass. The present study suggested that the ΔkasB gene might be involved in the synthesis of extracellular cell-wall lipids in N. seriolae and play a crucial role in its pathogenicity.


Asunto(s)
Lubina , Enfermedades de los Peces , Nocardiosis , Nocardia , Animales , Virulencia/genética , Enfermedades de los Peces/microbiología , Nocardia/genética , Nocardiosis/veterinaria , Nocardiosis/microbiología
2.
Curr Issues Mol Biol ; 45(3): 1889-1901, 2023 Feb 27.
Artículo en Inglés | MEDLINE | ID: mdl-36975492

RESUMEN

Meibomian gland dysfunction (MGD) is a functional and morphological disorder of the meibomian glands which results in qualitative or quantitative alteration in meibum secretion and is the major cause of evaporative dry eye (EDE). EDE is often characterized by tear film instability, increased evaporation, hyperosmolarity, inflammation, and ocular surface disorder. The precise pathogenesis of MGD remains elusive. It has been widely considered that MGD develops as a result of ductal epithelial hyperkeratinization, which obstructs the meibomian orifice, halts meibum secretion, and causes secondary acinar atrophy and gland dropout. Abnormal self-renewal and differentiation of the acinar cells also play a significant role in MGD. This review summarizes the latest research findings regarding the possible pathogenesis of MGD and provides further treatment strategies for MGD-EDE patients.

3.
Rheumatology (Oxford) ; 62(3): 1087-1096, 2023 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-35946529

RESUMEN

OBJECTIVE: The most used drug for the treatment of rheumatoid arthritis (RA) remains methotrexate (MTX). Unfortunately, up to 50% of patients do not achieve a clinically adequate outcome. Here we study whether the gut microbiota patterns can aid in the prediction of MTX efficacy for RA. METHOD: To dissect gut microbiome profiles of RA patients (n = 145), 16S rRNA gene sequencing was performed. Dirichlet multinomial mixture (DMM) clustering was used to identify enterotypes at genus level. The relationships between enterotypes and clinical measures (such as lymphocyte subsets and cytokines detected by flow cytometry) were explored. Then, enterotype stability was evaluated by the stratification of the RA patient cohort (n = 66) in Shanghai, China, using the same method. Finally, the enterotype-based gut microbial human index classifier was applied to another independent RA patient cohort (n = 27) to identify the factors associated with MTX clinical response. RESULTS: Our analysis revealed that the RA patients always displayed two different dysbiotic microbiota patterns: RA E1 comprised predominantly Prevotella and RA E2 comprised predominantly Bacteroides. Among all of the lymphocyte subsets and cytokines, only the number of CD8+ T cells showed a significant difference between RA E1 and RA E2. These results were validated in the RA patient cohort in Shanghai, China. Significant associations of RA E1 with clinical response to subsequent MTX treatment were confirmed by another independent RA patient cohort. CONCLUSION: Together, the enterotype-based gut microbial human index (EGMI) classifier was useful to precisely and effectively identify enterotypes of individual RA patients, which could effectively evaluate MTX clinical responses.


Asunto(s)
Artritis Reumatoide , Microbioma Gastrointestinal , Humanos , Metotrexato/uso terapéutico , ARN Ribosómico 16S/genética , China , Artritis Reumatoide/tratamiento farmacológico , Citocinas
4.
Blood ; 138(9): 806-810, 2021 09 02.
Artículo en Inglés | MEDLINE | ID: mdl-34473230

RESUMEN

PD-L1 is a ligand for PD-1, and its expression has been shown to be upregulated in neutrophils harvested from septic patients. However, the effect of PD-L1 on neutrophil survival and sepsis-induced lung injury remains largely unknown. In this study, PD-L1 expression correlated negatively with rates of apoptosis in human neutrophils harvested from patients with sepsis. Coimmunoprecipitation assays on control neutrophils challenged with interferon-γ and LPS showed that PD-L1 complexes with the p85 subunit of phosphatidyl 3-kinase (PI3K) to activate AKT-dependent survival signaling. Conditional CRE/LoxP deletion of neutrophil PD-L1 in vivo further protected against lung injury and reduced neutrophil lung infiltration in a cecal ligation and puncture (CLP) experimental sepsis animal model. Compared with wild-type animals, PD-L1-deficient animals presented lower levels of plasma tumor necrosis factor-α and interleukin-6 (IL-6) and higher levels of IL-10 after CLP, and reduced 7-day mortality in CLP PD-L1-knockout animals. Taken together, our data suggest that increased PD-L1 expression on human neutrophils delays cellular apoptosis by triggering PI3K-dependent AKT phosphorylation to drive lung injury and increase mortality during clinical and experimental sepsis.


Asunto(s)
Lesión Pulmonar Aguda/inmunología , Apoptosis/inmunología , Antígeno B7-H1/inmunología , Neutrófilos/inmunología , Sepsis/inmunología , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/genética , Lesión Pulmonar Aguda/patología , Animales , Apoptosis/genética , Antígeno B7-H1/genética , Modelos Animales de Enfermedad , Femenino , Humanos , Masculino , Ratones , Ratones Transgénicos , Neutrófilos/patología , Sepsis/complicaciones , Sepsis/genética , Sepsis/patología
5.
Exp Eye Res ; 231: 109470, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37059216

RESUMEN

Meibomian glands (MGs) are vital for ocular surface health. However, the roles of inflammation in the progression of meibomian gland dysfunction (MGD) are largely unknown. In this study, the roles of the inflammation factor interleukin-1ß (IL-1ß) via the p38 mitogen-activated protein kinases (MAPK) signaling pathway on rat meibomian gland epithelial cells (RMGECs) were explored. Eyelids from adult rat mice at 2 months and 2 years of age were stained with specific antibodies against IL-1ß to identify inflammation levels. RMGECs were exposed to IL-1ß and/or SB203580, a specific inhibitor of p38 MAPK signaling pathway, for 3 days. Cell proliferation, keratinization, lipid accumulation, and matrix metalloproteinases 9 (MMP9) expression were evaluated by MTT assay, polymerase chain reaction (PCR), immunofluorescence staining, apoptosis assay, lipid staining, and Western blot analyses. We found that IL-1ß was significantly higher in the terminal ducts of MGs in rats with age-related MGD than in young rats. IL-1ß inhibited cell proliferation, suppressed lipid accumulation and peroxisome proliferator activator receptor γ (PPARγ) expression, and promoted apoptosis while activating the p38 MAPK signaling pathway. Cytokeratin 1 (CK1), a marker for complete keratinization, and MMP9 in RMGECs were also up-regulated by IL-1ß. SB203580 effectively diminished the effects of IL-1ß on differentiation, keratinization, and MMP9 expression by blocking IL-1ß-induced p38 MAPK activation, although it also inhibited cell proliferation. The inhibition of the p38 MAPK signaling pathway blocked IL-1ß-induced differentiation reduction, hyperkeratinization, and MMP9 overexpression of RMGECs, which provides a potential therapy for MGD.


Asunto(s)
Glándulas Tarsales , Proteínas Quinasas p38 Activadas por Mitógenos , Ratas , Ratones , Animales , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Glándulas Tarsales/metabolismo , Sistema de Señalización de MAP Quinasas/fisiología , Metaloproteinasa 9 de la Matriz/metabolismo , Interleucina-1beta/farmacología , Interleucina-1beta/metabolismo , Células Epiteliales/metabolismo , Inflamación/metabolismo , Lípidos
6.
J Fish Dis ; 46(3): 229-238, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36484113

RESUMEN

Pseudomonas plecoglossicida is an important pathogenic bacterium in aquaculture that causes visceral granulomas in large yellow croaker (Larimichthys crocea). Uridine diphosphate glucose phosphorylase encoded by galU plays a key role in biosynthesis of the bacterial envelope, particularly lipopolysaccharide and the capsule. In this study, we inactivated the galU gene in the P. plecoglossicida isolate XSDHY-P. The galU mutant strain showed impaired growth in the early exponential stage and lacked the O polysaccharide side chain in lipopolysaccharide, but almost no defect in biofilm formation was detected. The galU mutant strain also exhibited significantly more sensitivity to the bactericidal action of normal fish serum mediated by the complement system compared to the wild-type strain. In a cell model originating from the head kidney of large yellow croaker, the galU mutant strain showed lower capacities of adhesion, invasion, and intracellular survival compared to the wild-type strain. In addition, the deficiency of the galU mutant drastically decreased bacterial loads in tissues and attenuated P. plecoglossicida virulence in fish. These results suggest that the galU gene of P. plecoglossicida is required for in vivo survival in large yellow croaker.


Asunto(s)
Enfermedades de los Peces , Perciformes , Infecciones por Pseudomonas , Animales , Infecciones por Pseudomonas/microbiología , Lipopolisacáridos , Enfermedades de los Peces/microbiología , Perciformes/microbiología
7.
Int Orthop ; 47(3): 773-779, 2023 03.
Artículo en Inglés | MEDLINE | ID: mdl-36629850

RESUMEN

PURPOSE: Radial and ulnar fractures are one of the most common fractures in children. When closed reduction of fractures fails, elastic stable intramedullary nail (ESIN) fixation can mostly be used under the guidance of fluoroscopy. In this study, we evaluated the effect of ultrasound (US) as assistance for radial and ulnar fracture reduction and the insertion of ESINs. METHODS: There were 56 patients with midshaft radial and ulnar fractures included in our hospital from March 2019 to August 2021. After applying the inclusion and exclusion criteria and according to the treatment method, they were divided into the US group (patients treated with US assistance) and the conventional group (C-group, patients treated with fluoroscopy guidance). All patients' clinical data were collected. Operation time, fluoroscopy times, radiation dose, and post-operative complications were analyzed. The elbow function was evaluated using the Mayo Elbow Performance Index. RESULTS: There were 26 patients in the US group and 30 in the C-group. The average operation time was 44.5±19.4 min in the US group and 65.1±16.2 min in the C-group. There were significant differences regarding the surgery time, fluoroscopy time, and radiation dose between the groups (all p = 0.001). The average follow-up time was 13.5±3.1 months. No significant difference was found regarding radial nerve injury, extensor pollicis longus rupture, non-union or delayed union, ulnar nerve injury, or acute compartment syndrome. There was no difference in elbow function at the final follow-up. CONCLUSION: US guidance can be adopted for the treatment of displaced radial and ulnar fracture reduction and the insertion of ESINs. It can significantly decrease fluoroscopy times, radiation doses, and duration of surgery.


Asunto(s)
Fijación Intramedular de Fracturas , Fracturas Óseas , Fracturas del Radio , Fracturas del Cúbito , Humanos , Niño , Radio (Anatomía) , Fracturas Óseas/etiología , Fijación Interna de Fracturas , Fijación Intramedular de Fracturas/efectos adversos , Fijación Intramedular de Fracturas/métodos , Clavos Ortopédicos , Fracturas del Cúbito/diagnóstico por imagen , Fracturas del Cúbito/cirugía , Estudios Retrospectivos , Resultado del Tratamiento , Fracturas del Radio/diagnóstico por imagen , Fracturas del Radio/cirugía
8.
BMC Genomics ; 22(1): 94, 2021 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-33522906

RESUMEN

BACKGROUND: Paeonia lactiflora 'Hangshao' is widely cultivated in China as a traditional Chinese medicine 'Radix Paeoniae Alba'. Due to the abundant unsaturated fatty acids in its seed, it can also be regarded as a new oilseed plant. However, the process of the biosynthesis of unsaturated fatty acids in it has remained unknown. Therefore, transcriptome analysis is helpful to better understand the underlying molecular mechanisms. RESULTS: Five main fatty acids were detected, including stearic acid, palmitic acid, oleic acid, linoleic acid and α-linolenic acid, and their absolute contents first increased and then decreased during seed development. A total of 150,156 unigenes were obtained by transcriptome sequencing. There were 15,005 unigenes annotated in the seven functional databases, including NR, NT, GO, KOG, KEGG, Swiss-Prot and InterPro. Based on the KEGG database, 1766 unigenes were annotated in the lipid metabolism. There were 4635, 12,304, and 18,291 DEGs in Group I (60 vs 30 DAF), Group II (90 vs 60 DAF) and Group III (90 vs 30 DAF), respectively. A total of 1480 DEGs were detected in the intersection of the three groups. In 14 KEGG pathways of lipid metabolism, 503 DEGs were found, belonging to 111 enzymes. We screened out 123 DEGs involved in fatty acid biosynthesis (39 DEGs), fatty acid elongation (33 DEGs), biosynthesis of unsaturated fatty acid (24 DEGs), TAG assembly (17 DEGs) and lipid storage (10 DEGs). Furthermore, qRT-PCR was used to analyze the expression patterns of 16 genes, including BBCP, BC, MCAT, KASIII, KASII, FATA, FATB, KCR, SAD, FAD2, FAD3, FAD7, GPAT, DGAT, OLE and CLO, most of which showed the highest expression at 45 DAF, except for DGAT, OLE and CLO, which showed the highest expression at 75 DAF. CONCLUSIONS: We predicted that MCAT, KASIII, FATA, SAD, FAD2, FAD3, DGAT and OLE were the key genes in the unsaturated fatty acid biosynthesis and oil accumulation in herbaceous peony seed. This study provides the first comprehensive genomic resources characterizing herbaceous peony seed gene expression at the transcriptional level. These data lay the foundation for elucidating the molecular mechanisms of fatty acid biosynthesis and oil accumulation for herbaceous peony.


Asunto(s)
Paeonia , China , Ácidos Grasos Insaturados , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Paeonia/genética , Semillas/genética , Transcriptoma
9.
Neurochem Res ; 46(4): 964-979, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33586092

RESUMEN

Alzheimer's disease (AD) is a growing health concern worldwide. MicroRNAs (miRNAs) have been extensively studied in many diseases, including AD. To identify differentially expressed miRNAs (DEmiRNAs) and genes specific to AD, we used bioinformatic analyses to investigate candidate miRNA-mRNA pairs involved in the pathogenesis of AD. We focused on differentially expressed genes (DEGs) that are targets of DEmiRNAs. The GEO2R tool and the HISAT2-DESeq2 software were used to identify DEmiRNAs and DEGs. Bioinformatic tools available online, such as TAM and the Database for Annotation, Visualization and Integrated Discovery (DAVID), were used to perform functional annotation and enrichment analysis. Targets of miRNAs were predicted using the miRTarBase. The Search Tool for the Retrieval of Interacting Genes (STRING) and Cytoscape, which are available online, were utilized to construct protein-protein interaction (PPI) networks and identify hub genes. Furthermore, transcription factors (TFs) encoded by the DEGs were predicted using the TransmiR database and TF-miRNA-mRNA networks were constructed. Finally, the expression profile of a hub gene in peripheral blood mononuclear cells was compared between healthy individuals and AD patients. We identified 26 correlated miRNA-mRNA pairs. In the parietal lobe, miRNA-mRNA pairs involved in protein folding were enriched, and in the frontal lobe, miRNA-mRNA pairs involved in synaptic transmission, abnormal protein degradation, and apoptosis were enriched. In addition, HSP90AB1 in peripheral blood mononuclear cells was found to be significantly downregulated in AD patients, and this was consistent with its expression profile in the parietal lobe of AD patients. Our results provide brain region-specific changes in miRNA-mRNA associations in AD patients, further our understanding of potential underlying molecular mechanisms of AD, and reveal promising diagnostic and therapeutic targets for AD.


Asunto(s)
Enfermedad de Alzheimer/metabolismo , Lóbulo Frontal/metabolismo , MicroARNs/metabolismo , Lóbulo Parietal/metabolismo , ARN Mensajero/metabolismo , Enfermedad de Alzheimer/genética , Biología Computacional , Bases de Datos Genéticas , Regulación hacia Abajo , Perfilación de la Expresión Génica , Ontología de Genes , Humanos , MicroARNs/genética , Mapas de Interacción de Proteínas , ARN Mensajero/genética , Regulación hacia Arriba
10.
Acta Pharmacol Sin ; 42(7): 1069-1079, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-33758353

RESUMEN

Sepsis is life-threatening organ dysfunction due to dysregulated systemic inflammatory and immune response to infection, often leading to cognitive impairments. Growing evidence shows that artemisinin, an antimalarial drug, possesses potent anti-inflammatory and immunoregulatory activities. In this study we investigated whether artemisinin exerted protective effect against neurocognitive deficits associated with sepsis and explored the underlying mechanisms. Mice were injected with LPS (750 µg · kg-1 · d-1, ip, for 7 days) to establish an animal model of sepsis. Artemisinin (30 mg · kg-1 · d-1, ip) was administered starting 4 days prior LPS injection and lasting to the end of LPS injection. We showed that artemisinin administration significantly improved LPS-induced cognitive impairments assessed in Morris water maze and Y maze tests, attenuated neuronal damage and microglial activation in the hippocampus. In BV2 microglial cells treated with LPS (100 ng/mL), pre-application of artemisinin (40 µΜ) significantly reduced the production of proinflammatory cytokines (i.e., TNF-α, IL-6) and suppressed microglial migration. Furthermore, we revealed that artemisinin significantly suppressed the nuclear translocation of NF-κB and the expression of proinflammatory cytokines by activating the AMPKα1 pathway; knockdown of AMPKα1 markedly abolished the anti-inflammatory effects of artemisinin in BV2 microglial cells. In conclusion, atemisinin is a potential therapeutic agent for sepsis-associated neuroinflammation and cognitive impairment, and its effect is probably mediated by activation of the AMPKα1 signaling pathway in microglia.


Asunto(s)
Artemisininas/uso terapéutico , Microglía/efectos de los fármacos , Trastornos Neurocognitivos/tratamiento farmacológico , Fármacos Neuroprotectores/uso terapéutico , Sepsis/tratamiento farmacológico , Transducción de Señal/efectos de los fármacos , Proteínas Quinasas Activadas por AMP/metabolismo , Animales , Antiinflamatorios/uso terapéutico , Región CA1 Hipocampal/efectos de los fármacos , Región CA1 Hipocampal/patología , Muerte Celular/efectos de los fármacos , Línea Celular , Movimiento Celular/efectos de los fármacos , Citocinas/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/etiología , Inflamación/metabolismo , Lipopolisacáridos , Masculino , Ratones Endogámicos C57BL , Microglía/metabolismo , Prueba del Laberinto Acuático de Morris/efectos de los fármacos , Trastornos Neurocognitivos/etiología , Trastornos Neurocognitivos/metabolismo , Neuronas/efectos de los fármacos , Sepsis/inducido químicamente , Sepsis/complicaciones , Sepsis/metabolismo
11.
Mol Ther ; 28(2): 572-586, 2020 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-31732298

RESUMEN

MicroRNA24-2 (miR24-2) is associated with human tumorigenesis; however, its molecular mechanisms are poorly understood. Herein, our findings demonstrate that miR24-2 promotes the proliferation ability in vitro and the tumorigenic ability in vivo in human liver cancer stem cells (hLCSCs). Mechanically, the miR24-2 targets for 3' UTR (2,627-2,648) of protein arginine methyltransferase 7 (PRMT7) inhibit the translational ability of prmt7 gene. Moreover, miR24-2 inhibits the di-/tri-methylation of histone H4 arginine 3 by reducing PRMT7 and then promotes the expression of Nanog via long noncoding RNA HULC. Notably, miR24-2 inhibits histone deacetylase HDAC3 through miR675, which promotes the acetylation of histone H4 at lysine 16. Subsequently, miR24-2 enhances the interaction between LC3 and ATG4 dependent on PI3K and triggers cellular autophagy. Strikingly, miR24-2 inhibits the degradation of pyruvate kinase M1 via autophagosome-P62 in hLCSCs. Furthermore, miR24-2 enhances the activity of Src by promoting the binding of PKM1 to the Src promoter regions in hLCSCs. In particular, our results also indicate that src gene determines the oncogenic functions of miR24-2. These results provided a valuable theoretical basis for the discovery of liver cancer therapeutic targets and diagnosis markers based on miR24-2.


Asunto(s)
Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , MicroARNs/genética , Células Madre Neoplásicas/metabolismo , Familia-src Quinasas/genética , Acetilación , Autofagia , Proteínas Portadoras/metabolismo , Línea Celular Tumoral , Progresión de la Enfermedad , Histonas/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Proteínas de la Membrana/metabolismo , Metilación , Proteína Homeótica Nanog/genética , Proteína-Arginina N-Metiltransferasas/genética , Interferencia de ARN , Hormonas Tiroideas/metabolismo , Proteínas de Unión a Hormona Tiroide
12.
Mediators Inflamm ; 2021: 5927064, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34257516

RESUMEN

BACKGROUND AND AIMS: Recent evidences reveal that epithelial to mesenchymal transition (EMT) exacerbates the process of intestinal fibrosis. Tumor necrosis factor-like ligand 1A (TL1A) is a member of the tumor necrosis family (TNF), which can take part in the development of colonic inflammation and fibrosis by regulating immune response or inflammatory factors. The purpose of this study was to elucidate the possible contribution of TL1A in onset and progression of intestinal inflammation and fibrosis through EMT. METHODS: Colonic specimens were obtained from patients with inflammatory bowel disease (IBD) and control individuals. The expression levels of TL1A and EMT-related markers in intestinal tissues were evaluated. Furthermore, the human colorectal adenocarcinoma cell line, HT-29, was stimulated with TL1A, anti-TL1A antibody, or BMP-7 to assess EMT process. In addition, transgenic mice expressing high levels of TL1A in lymphoid cells were used to further investigate the mechanism of TL1A in intestinal fibrosis. RESULTS: High levels of TL1A expression were detected in the intestinal specimens of patients with ulcerative colitis and Crohn's disease and were negatively associated with the expression of an epithelial marker (E-cadherin), while it was positively associated with the expression of interstitial markers (FSP1 and α-SMA). Transgenic mice with high expression of TL1A were more sensitive to dextran sodium sulfate and exhibited severe intestinal inflammation and fibrosis. Additionally, the TGF-ß1/Smad3 pathway may be involved in TL1A-induced EMT, and the expression of IL-13 and EMT-related transcriptional molecules (e.g., ZEB1 and Snail1) was increased in the intestinal specimens of the transgenic mice. Furthermore, TL1A-induced EMT can be influenced by anti-TL1A antibody or BMP-7 in vitro. CONCLUSIONS: TL1A participates in the formation and process of EMT in intestinal fibrosis. This new knowledge enables us to better understand the pathogenesis of intestinal fibrosis and identify new therapeutic targets for its treatment.


Asunto(s)
Colitis/metabolismo , Transición Epitelial-Mesenquimal , Fibrosis/metabolismo , Intestinos/metabolismo , Miembro 15 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral/metabolismo , Adulto , Animales , Proteína Morfogenética Ósea 7/metabolismo , Cadherinas/metabolismo , Enfermedad Crónica , Femenino , Células HT29 , Humanos , Sistema Inmunológico , Inflamación , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Transgénicos , Persona de Mediana Edad , Reproducibilidad de los Resultados
13.
Food Microbiol ; 95: 103684, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33397616

RESUMEN

Shanxi aged vinegar (SAV), a Chinese traditional vinegar, is produced by various microorganisms. Ammonium is an important nitrogen source for microorganisms and a key intermediate for the utilization of non-ammonium nitrogen sources. In this work, an ammonium metabolic network during SAV fermentation was constructed through the meta-transcriptomic analysis of in situ samples, and the potential mechanism of acid affecting ammonium metabolism was revealed. The results showed that ammonium was enriched as the acidity increased. Meta-transcriptomic analysis showed that the conversion of glutamine to ammonia is the key pathway of ammonium metabolism in vinegar and that Lactobacillus and Acetobacter are the dominant genera. The construction and analysis of the metabolic network showed that amino acid metabolism, nucleic acid metabolism, pentose phosphate pathway and energy metabolism were enhanced to resist acid damage to the intracellular environment and cell structures. The enhancement of nitrogen assimilation provides nitrogen for metabolic pathways that resist acid cytotoxicity. In addition, the concentration gradient allows ammonium to diffuse outside the cell, which causes ammonium to accumulate during fermentation.


Asunto(s)
Ácido Acético/metabolismo , Acetobacter/metabolismo , Compuestos de Amonio/metabolismo , Grano Comestible/microbiología , Lactobacillus/metabolismo , Grano Comestible/metabolismo , Fermentación , Redes y Vías Metabólicas
14.
J Cell Mol Med ; 24(5): 2772-2790, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32030886

RESUMEN

Several microRNAs are associated with carcinogenesis and tumour progression. Herein, our observations suggest both miR24-2 and Pim1 are up-regulated in human liver cancers, and miR24-2 accelerates growth of liver cancer cells in vitro and in vivo. Mechanistically, miR24-2 increases the expression of N6-adenosine-methyltransferase METTL3 and thereafter promotes the expression of miR6079 via RNA methylation modification. Furthermore, miR6079 targets JMJD2A and then increased the tri-methylation of histone H3 on the ninth lysine (H3K9me3). Therefore, miR24-2 inhibits JMJD2A by increasing miR6079 and then increases H3K9me3. Strikingly, miR24-2 increases the expression of Pim1 dependent on H3K9me3 and METTL3. Notably, our findings suggest that miR24-2 alters several related genes (pHistone H3, SUZ12, SUV39H1, Nanog, MEKK4, pTyr) and accelerates progression of liver cancer cells through Pim1 activation. In particular, Pim1 is required for the oncogenic action of miR24-2 in liver cancer. This study elucidates a novel mechanism for miR24-2 in liver cancer and suggests that miR24-2 may be used as novel therapeutic targets of liver cancer.


Asunto(s)
Progresión de la Enfermedad , Histonas/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patología , Lisina/metabolismo , MicroARNs/metabolismo , Proteínas Proto-Oncogénicas c-pim-1/metabolismo , Animales , Secuencia de Bases , Línea Celular Tumoral , Proliferación Celular/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Histona Demetilasas con Dominio de Jumonji/metabolismo , Masculino , Metilación , Metiltransferasas/genética , Metiltransferasas/metabolismo , Ratones Endogámicos BALB C , Ratones Desnudos , MicroARNs/genética , Modelos Biológicos , Oncogenes , Proteínas Proto-Oncogénicas c-pim-1/genética
15.
Cryobiology ; 94: 95-99, 2020 06.
Artículo en Inglés | MEDLINE | ID: mdl-32304703

RESUMEN

Sperm cryopreservation is an essential approach for assisted reproduction and genetic resources conservation in captive giant pandas. Cryopreservation, however, leads to a significant decrease in sperm quality and, consequently, a low fertilization rate. Therefore, it is mandatory to disclose more suitable and efficient freezing strategies for sperm cryopreservation. In the present study, we compared for the first time the performance of two commercial freeze extender (INRA96 versus TEST) freezing methods on post-thawed semen quality. Semen cryopreserved with the INRA96 showed better total motility (73.00 ± 4.84% vs 57.56 ± 3.60%, P < 0.001), membrane integrity (60.92 ± 2.27% vs 40.53 ± 2.97%, P < 0.001) and acrosome integrity (90.39 ± 2.74% vs 84.26 ± 4.27%, P < 0.05) than stored with TEST. There was no significant difference in DNA integrity after thawing between the two extenders (95.69 ± 3.60% vs 94.26 ± 4.84%). In conclusion, the INRA96 method showed to be better for giant panda sperm cryopreservation and should therefore be recommended for use in order to increase success of artificial insemination.


Asunto(s)
Criopreservación/métodos , Crioprotectores/farmacología , Preservación de Semen/métodos , Semen , Ursidae , Animales , Masculino , Análisis de Semen , Espermatozoides/efectos de los fármacos
17.
Fish Physiol Biochem ; 46(5): 1873-1882, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32617789

RESUMEN

Hypoxia stress may affect the fish intestine and thereby threaten the growth and survival of the fish. Teprenone is a clinically effective agent in protecting gastrointestinal mucosa. This study aims to assess the effect of teprenone in the intestine of Chinese sea bass Lateolabrax maculatus under intermittent hypoxic stress. L. maculatus juveniles were either raised under intermittent hypoxic condition or normal condition (NC). Part of the hypoxic-intervened fish were treated with teprenone at different concentrations (HTs), and the rest were regarded as hypoxic control (HC). Histological analysis was performed on the epithelial tissue of the fish intestine. High-throughput sequencing technology was used to analyze the diversity and composition of the microbial community in L. maculatus intestine. Reduced villi length and goblet cell, exfoliated enterocyte, and improper arrangement of villi were observed in HC compared with NC and HTs. Proteobacteria, Firmicutes, and Bacteroidetes represented the most abundant phyla in each sample. Significantly higher microbial diversity was detected in HC compared with NC (P < 0.05). At the phylum level, HC presented significantly decreased relative abundance of Proteobacteria, and significantly increased relative abundance of Bacteroidetes, Chloroflex, and Cyanobacteria compared with NC (P < 0.05). At the class level, HC showed significantly reduced relative abundance of Alphaproteobacteria and Bacilli, and significantly increased relative abundance of Clostridia, Gammaproteobacteria, and Bacteroides (P < 0.05). Teprenone protects the intestine from epithelial damages and maintains the microbial harmony in L. maculatus under intermittent hypoxic stress.


Asunto(s)
Antiulcerosos/farmacología , Lubina , Diterpenos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Intestinos/efectos de los fármacos , Animales , Bacterias/clasificación , Bacterias/efectos de los fármacos , Intestinos/patología
18.
BMC Ophthalmol ; 19(1): 136, 2019 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-31242876

RESUMEN

BACKGROUND: To report a case of non-prescription cold and flu medication-induced transient myopia with uveal effusion. CASE PRESENTATION: Bilateral high intraocular pressure, shallow anterior chambers, uveal effusion, and a myopic shift were encountered in a 39-year-old Chinese male 1 night after taking a non-prescription flu medicine three times than the recommended dose. Ultrasound biomicroscopy (UBM) showed bilateral ciliochoroidal effusions, disappearance of the ciliary sulcus, closure of the angle of the anterior chamber, and anterior displacement of the lens-iris diaphragm. Treatment with aqueous suppressants was given. Within a week, the uncorrected vision restored, and the myopia had disappeared. UBM revealed major resolution of the ciliochoroidal effusions in both eyes, deepening of the anterior chamber, return of the lens-iris diaphragm to a more posterior position. CONCLUSIONS: Overdose of non-prescription cold and flu medication may cause bilateral uveal effusions inducing acute angle-closure glaucoma and acute myopia.


Asunto(s)
Medicamentos Compuestos contra Resfriado, Gripe y Alergia/efectos adversos , Miopía/inducido químicamente , Refracción Ocular/fisiología , Enfermedades de la Úvea/inducido químicamente , Agudeza Visual , Enfermedad Aguda , Adulto , Cuerpo Ciliar/diagnóstico por imagen , Exudados y Transudados , Humanos , Gripe Humana/tratamiento farmacológico , Masculino , Microscopía Acústica , Miopía/diagnóstico , Miopía/fisiopatología , Medicamentos sin Prescripción/efectos adversos , Enfermedades de la Úvea/diagnóstico
19.
Pestic Biochem Physiol ; 156: 56-62, 2019 May.
Artículo en Inglés | MEDLINE | ID: mdl-31027581

RESUMEN

Glutamate-gated chloride channels (GluCls) mediate inhibitory synaptic transmission in invertebrate nervous systems, and only one GluCl gene has been found in insects. Therefore, insect GluCls are one of the major targets of insecticides including avermectins. In the present study, a 1347 bp full-length cDNA encoding a 449-amino acid protein (named MsGluCl, GenBank ID: MK336885) was cloned from the oriental armyworm, Mythimna separata, and characterized two alternative splicing variants of MsGluCl. The protein shares 76.9-98.6% identity with other insect GluCl isoforms. Spatial and temporal expression analysis revealed that MsGluCl was highly expressed in the 3rd instar and adult head. Dietary ingestion of dsMsGluCl significantly reduced the mRNA level of MsGluCl and decreased abamectin mortality. Thus, our results reveal that MsGluCl could be the molecular target of abamectin and provide the basis for further understanding the resistance mechanism to abamectin in arthropods.


Asunto(s)
Empalme Alternativo/genética , Canales de Cloruro/metabolismo , Clonación Molecular/métodos , Mariposas Nocturnas/genética , Animales , Canales de Cloruro/genética , ADN Complementario/genética , ADN Complementario/metabolismo , Insecticidas/farmacología , Ivermectina/análogos & derivados , Ivermectina/farmacología , Mariposas Nocturnas/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo
20.
Pestic Biochem Physiol ; 157: 186-195, 2019 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-31153467

RESUMEN

The sugarcane shoot borer Chilo infuscatellus (Snellen) is known for causing severe damage to sugarcane yield in China. Methods have been developed to control this pest, including Cry toxin pesticide and transgenic Bt plants. In order to investigate the molecular mechanism of the Cry toxin binding process and provide a basis for understanding the insect's resistance mechanism, we used a high throughput sequencing platform to perform a de novo transcriptome assembly across different larval developmental stages and analyzed Cry toxin receptors based on our assembled transcripts. We cloned twelve Cry toxin receptor genes including 1 cadherin (Cad), 7 aminopeptidase-Ns (APNs), 3 alkaline phosphatases (ALPs), and 1 ATP-binding cassette transporter subfamily C2 (ABCC2), and three of them with full length. The sublethal dosage of Cry1Ac toxin was applied to sugarcane shoot borer and identified some Cry toxin receptor genes that were significantly induced after 48 h of exposure. Furthermore, quantitative RT-PCR was conducted to detect the expression profiles of these genes. Our transcriptome sequence data provided a valuable molecular resource for further study and the identified Cry toxin receptor data gave insights for improved research into the mechanism of Bt resistance.


Asunto(s)
Proteínas Bacterianas/metabolismo , Proteínas Hemolisinas/metabolismo , Plantas Modificadas Genéticamente/metabolismo , Saccharum/metabolismo , Animales , Toxinas de Bacillus thuringiensis , Proteínas Bacterianas/genética , Endotoxinas/genética , Endotoxinas/metabolismo , Proteínas Hemolisinas/genética , Resistencia a los Insecticidas/genética , Mariposas Nocturnas , Plantas Modificadas Genéticamente/genética , Saccharum/genética
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