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1.
Int J Biol Macromol ; 276(Pt 1): 133732, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-39002919

RESUMO

γ-aminobutyric acid (GABA) plays an important role in anti-anxiety by inhibiting neurotransmitter in the central nervous system (CNS) of mammals, which is generated in the germinating seeds. The key enzymes activity of GABA metabolism pathway and nutrients content in hemp seeds during germination were studied after treated with ultrasound and CaCl2. The mechanism of exogenous stress on key enzymes in GABA metabolism pathway was investigated by molecular dynamics simulation. The results showed that ultrasonic combined with 1.5 mmol·L-1CaCl2 significantly increased the activities of glutamate decarboxylase (GAD) and GABA transaminase (GABA-T) in seeds, and promoted the conversion of glutamate to GABA, resulting in the decrease of glutamate content and the accumulation of GABA. Molecular dynamics simulations revealed that Ca2+ environment enhanced the activity of GAD and GABA-T enzymes by altering their secondary structure, exposing their hydrophobic residues. Ultrasound, germination and CaCl2 stress improved the nutritional value of hemp seeds.

2.
Nat Commun ; 15(1): 5800, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987276

RESUMO

Enhancing influenza vaccine cross-protection is imperative to alleviate the significant public health burden of influenza. Heterologous sequential immunization may synergize diverse vaccine formulations and routes to improve vaccine potency and breadth. Here we investigate the effects of immunization strategies on the generation of cross-protective immune responses in female Balb/c mice, utilizing mRNA lipid nanoparticle (LNP) and protein-based PHC nanoparticle vaccines targeting influenza hemagglutinin. Our findings emphasize the crucial role of priming vaccination in shaping Th bias and immunodominance hierarchies. mRNA LNP prime favors Th1-leaning responses, while PHC prime elicits Th2-skewing responses. We demonstrate that cellular and mucosal immune responses are pivotal correlates of cross-protection against influenza. Notably, intranasal PHC immunization outperforms its intramuscular counterpart in inducing mucosal immunity and conferring cross-protection. Sequential mRNA LNP prime and intranasal PHC boost demonstrate optimal cross-protection against antigenically drifted and shifted influenza strains. Our study offers valuable insights into tailoring immunization strategies to optimize influenza vaccine effectiveness.


Assuntos
Administração Intranasal , Proteção Cruzada , Vacinas contra Influenza , Camundongos Endogâmicos BALB C , Nanopartículas , Infecções por Orthomyxoviridae , Animais , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Nanopartículas/química , Feminino , Proteção Cruzada/imunologia , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/imunologia , Camundongos , Imunidade nas Mucosas/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/imunologia , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , RNA Mensageiro/genética , RNA Mensageiro/imunologia , Lipídeos/química , Anticorpos Antivirais/imunologia , Humanos , Imunização/métodos , Vacinação/métodos , Nanovacinas , Lipossomos
3.
Int J Biol Macromol ; 276(Pt 2): 134002, 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39032909

RESUMO

Cellulose-based fabrics have significant advantages, but their application scenarios are limited due to their flammability. This work used biomass phytic acid and protein decomposition products, alkaline amino acids (arginine, lysine, histidine) to prepare alkaline amino acid flame retardants (PALA, PALL, PALH), and they were utilized to endow Lyocell fabrics with flame-retardant and antibacterial properties. When the weight gain was about 16.0 wt%, PALA exhibited better flame-retardant effect, and the limited oxygen index value of PALA-Lyocell reached 47.1 %. In the cone calorimetry test, PALA showed the best flame-retardant efficiency in reducing flame growth index with a 92.0 % decrease in peak heat release rate. The results of thermogravimetric analysis coupled with Fourier Transform Infrared spectroscopy (TG-FTIR) and char residues indicated that the flame-retardant property of alkaline amino acid flame retardants was formed through the combined action of gas and condensed phases. In the antibacterial test, PALA had the highest antibacterial rate against Staphylococcus aureus at 97.2 %. Mechanical property, handle feeling, and whiteness results had indicated that alkaline amino acid based flame retardants had little effect on the physical properties of Lyocell fabrics. This work confirms alkaline amino acid based flame retardants have functions of flame-retardant and antibacterial properties, providing reference for the practical value of biomass in cellulose-based fabrics.

4.
Nat Commun ; 15(1): 5288, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38902277

RESUMO

Psoriasis is an immune-mediated skin disease associated with neurogenic inflammation, but the underlying molecular mechanism remains unclear. We demonstrate here that acid-sensing ion channel 3 (ASIC3) exacerbates psoriatic inflammation through a sensory neurogenic pathway. Global or nociceptor-specific Asic3 knockout (KO) in female mice alleviates imiquimod-induced psoriatic acanthosis and type 17 inflammation to the same extent as nociceptor ablation. However, ASIC3 is dispensable for IL-23-induced psoriatic inflammation that bypasses the need for nociceptors. Mechanistically, ASIC3 activation induces the activity-dependent release of calcitonin gene-related peptide (CGRP) from sensory neurons to promote neurogenic inflammation. Botulinum neurotoxin A and CGRP antagonists prevent sensory neuron-mediated exacerbation of psoriatic inflammation to similar extents as Asic3 KO. In contrast, replenishing CGRP in the skin of Asic3 KO mice restores the inflammatory response. These findings establish sensory ASIC3 as a critical constituent in psoriatic inflammation, and a promising target for neurogenic inflammation management.


Assuntos
Canais Iônicos Sensíveis a Ácido , Peptídeo Relacionado com Gene de Calcitonina , Camundongos Knockout , Psoríase , Células Receptoras Sensoriais , Animais , Canais Iônicos Sensíveis a Ácido/metabolismo , Canais Iônicos Sensíveis a Ácido/genética , Feminino , Psoríase/metabolismo , Psoríase/patologia , Psoríase/genética , Psoríase/induzido quimicamente , Camundongos , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Peptídeo Relacionado com Gene de Calcitonina/genética , Células Receptoras Sensoriais/metabolismo , Pele/metabolismo , Pele/patologia , Imiquimode , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Inflamação/metabolismo , Inflamação Neurogênica/metabolismo , Humanos , Nociceptores/metabolismo , Interleucina-23/metabolismo , Interleucina-23/genética
5.
FEBS J ; 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38944686

RESUMO

Within the three-dimensional (3D) nuclear space, the genome organizes into a series of orderly structures that impose important influences on gene regulation. T lymphocytes, crucial players in adaptive immune responses, undergo intricate transcriptional remodeling upon activation, leading to differentiation into specific effector and memory T cell subsets. Recent evidence suggests that T cell activation is accompanied by dynamic changes in genome architecture at multiple levels, providing a unique biological context to explore the functional relevance and molecular mechanisms of 3D genome organization. Here, we summarize recent advances that link the reorganization of genome architecture to the remodeling of transcriptional programs and conversion of cell fates during T cell activation and differentiation. We further discuss how various chromatin architecture regulators, including CCCTC-binding factor and several transcription factors, collectively modulate the genome architecture during this process.

6.
J Asian Nat Prod Res ; : 1-9, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38860546

RESUMO

Pegmolesatide, a synthetic, polyethylene-glycolylated, peptide-based erythropoiesis-stimulating agent (ESA), has been recently approved in China. Pegmolesatide is derived from the structure of endogenous erythropoietin (EPO), a natural product in mammals. This study compared the in vitro effects and selectivity of pegmolesatide to those of recombinant EPO and carbamylated EPO (CEPO) through computer-aided analyses and biological tests. The findings indicate that pegmolesatide exhibited the same stimulating effect on erythropoiesis as EPO with fewer side effects than EPO and CEPO.

8.
Chemosphere ; 362: 142597, 2024 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-38889873

RESUMO

In the past decades, the amount of biomass waste has continuously increased in human living environments, and it has attracted more and more attention. Biomass is regarded as the most high-quality and cost-effective precursor material for the preparation carbon of adsorbents and catalysts. The application of biomass carbon has extensively explored. The efficient application of biomass carbon in organic wastewater purification were reviewed. With briefly introducing biomass types, the latest progress of Machine learning in guiding the preparation and application of biomass carbon was emphasized. The key factors in constructing efficient biomass carbon for adsorption and catalytic applications were discussed. Based on the functional groups, rich pore structure and active site of biomass carbon, it exhibits high efficiency in water purification performance in the fields of adsorption and catalysis. In addition, out of a firm belief in the enormous potential of biomass carbon, the remaining challenges and future research directions were discussed.

9.
Arch Microbiol ; 206(7): 327, 2024 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-38922442

RESUMO

Lignocellulose biomass raw materials have a high value in energy conversion. Recently, there has been growing interest in using microorganisms to secret a series of enzymes for converting low-cost biomass into high-value products such as biofuels. We previously isolated a strain of Penicillium oxalicun 5-18 with promising lignocellulose-degrading capability. However, the mechanisms of lignocellulosic degradation of this fungus on various substrates are still unclear. In this study, we performed transcriptome-wide profiling and comparative analysis of strain 5-18 cultivated in liquid media with glucose (Glu), xylan (Xyl) or wheat bran (WB) as sole carbon source. In comparison to Glu culture, the number of differentially expressed genes (DEGs) induced by WB and Xyl was 4134 and 1484, respectively, with 1176 and 868 genes upregulated. Identified DEGs were enriched in many of the same pathways in both comparison groups (WB vs. Glu and Xly vs. Glu). Specially, 118 and 82 CAZyme coding genes were highly upregulated in WB and Xyl cultures, respectively. Some specific pathways including (Hemi)cellulose metabolic processes were enriched in both comparison groups. The high upregulation of these genes also confirmed the ability of strain 5-18 to degrade lignocellulose. Co-expression and co-upregulated of genes encoding CE and AA CAZy families, as well as other (hemi)cellulase revealed a complex degradation strategy in this strain. Our findings provide new insights into critical genes, key pathways and enzyme arsenal involved in the biomass degradation of P. oxalicum 5-18.


Assuntos
Perfilação da Expressão Gênica , Lignina , Penicillium , Transcriptoma , Xilanos , Penicillium/genética , Penicillium/metabolismo , Lignina/metabolismo , Xilanos/metabolismo , Biomassa , Glucose/metabolismo , Fibras na Dieta/metabolismo , Regulação Fúngica da Expressão Gênica , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo
10.
Diabetes Metab Syndr ; 18(5): 103023, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38697002

RESUMO

BACKGROUND: Epidemiological studies have consistently demonstrated a high prevalence of concurrent autoimmune diseases in individuals with Graves' disease (GD). OBJECTIVE: The objective of this study is to establish a causal association between GD and autoimmune diseases. METHODS: We employed a two-sample Mendelian randomization (MR) to infer a causal association between GD and five autoimmune diseases, namely rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Crohn's disease (CD), ulcerative colitis (UC), and amyotrophic lateral sclerosis (ALS), in the East Asian and European population. Genetic correlations were explored through linkage disequilibrium score regression analysis (LDSC). Finally, colocalization analyses were performed to investigate possible genetic foundations. RESULTS: Bidirectional MR analysis indicated that genetically predicted GD increased the risk of RA (Odds Ratio (OR): 1.34, 95 % Confidence Interval (CI): 1.21 to 1.47, P < 0.001) and SLE (OR: 1.21, 95%CI: 1.08 to 1.35, P < 0.001) in the East Asian population. In contrast, we found that genetically predicted RA (OR: 1.14, 95%CI: 1.05 to 1.24, P = 0.002) and SLE (OR: 1.10, 95%CI: 1.03 to 1.17, P = 0.003) were associated with a higher risk of GD. The results have been partially validated in European cohorts. Colocalization analysis suggested the potential existence of shared causal variants between GD and other autoimmune diseases. In particular, gene ARID5B may play an important role in the incidence of autoimmune diseases. CONCLUSION: This study has confirmed that GD was associated with RA and SLE and found a possible key gene ARID5B. It may be necessary to strengthen detection to prevent the occurrence of comorbidities in clinical practice.


Assuntos
Doenças Autoimunes , Doença de Graves , Análise da Randomização Mendeliana , Humanos , Doença de Graves/genética , Doença de Graves/epidemiologia , Doenças Autoimunes/genética , Doenças Autoimunes/epidemiologia , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Prognóstico , Fatores de Risco , Doença de Crohn/genética , Doença de Crohn/epidemiologia , Seguimentos , Lúpus Eritematoso Sistêmico/genética , Lúpus Eritematoso Sistêmico/epidemiologia , Artrite Reumatoide/genética , Artrite Reumatoide/epidemiologia
12.
Int J Surg ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38775550

RESUMO

BACKGROUND: Drug-eluting bead transarterial chemoembolization (DEB-TACE) has shown efficacy for treating hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT). However, whether DEB-TACE is superior to conventional TACE (cTACE) remains unclear. OBJECTIVE: This randomized controlled trial aimed to compare the efficacy and safety of DEB-TACE versus cTACE in treating HCC with PVTT. METHODS: The study was conducted in a tertiary care center in Southeast China. HCC patients with PVTT were randomized at a 1:1 ratio to the DEB-TACE or cTACE groups. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS) and incidence of adverse events (AEs). An independent review committee assessed the radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST). AEs were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. Systemic therapies were not limited. RESULTS: Between September 2018, and July 2020, 163 patients were randomized to undergo DEB-TACE (n=82) or cTACE (n=81). Nine patients were excluded, and 154 patients were included in the final analysis; the median age was 55 years (range, 24-78 y), and 140 (90.9%) were male. The median PFS in the DEB-TACE group was 6.0 months (95% CI, 5.0 to 10.0) versus 4.0 months (95% CI, 3.0 to 5.0) in the cTACE group (hazard ratio, 0.63; 95% CI, 0.42 to 0.95; P=0.027). The DEB-TACE group showed a higher response rate (51[66.2%] vs. 36 [46.8%]; P=0.0015) and a longer median OS (12.0 months [95% CI, 9.0 to 16.0] vs. 8.0 months [95% CI, 7.0 to 11.0], P=0.039) than the cTACE group. Multivariate analysis showed that the treatment group, ALBI score, distant metastasis and additional TKIs were the four independent prognostic factors correlated with PFS. In addition, the treatment group, PVTT group and combined with surgery were independently correlated with OS. AEs were similar in the two groups, and postembolization syndrome was the most frequent AEs. CONCLUSION: DEB-TACE is superior to cTACE in treating HCC patients with PVTT due to the improved PFS and OS with an acceptable safety profile and may become a promising treatment strategy for HCC patients with PVTT. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800018035.

13.
J Pharm Anal ; 14(5): 100929, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38799234

RESUMO

Analyzing polysorbate 20 (PS20) composition and the impact of each component on stability and safety is crucial due to formulation variations and individual tolerance. The similar structures and polarities of PS20 components make accurate separation, identification, and quantification challenging. In this work, a high-resolution quantitative method was developed using single-dimensional high-performance liquid chromatography (HPLC) with charged aerosol detection (CAD) to separate 18 key components with multiple esters. The separated components were characterized by ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) with an identical gradient as the HPLC-CAD analysis. The polysorbate compound database and library were expanded over 7-time compared to the commercial database. The method investigated differences in PS20 samples from various origins and grades for different dosage forms to evaluate the composition-process relationship. UHPLC-Q-TOF-MS identified 1329 to 1511 compounds in 4 batches of PS20 from different sources. The method observed the impact of 4 degradation conditions on peak components, identifying stable components and their tendencies to change. HPLC-CAD and UHPLC-Q-TOF-MS results provided insights into fingerprint differences, distinguishing quasi products.

14.
J Dig Dis ; 25(3): 191-199, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38697920

RESUMO

OBJECTIVE: To compare the detection rate and diagnostic accuracy of cardia polyps using endoscopy with blue laser imaging (BLI) and white-light imaging (WLI). METHODS: Patients were randomly divided into the BLI group and WLI group according to the endoscopic procedures. BLI followed by WLI was conducted in the BLI group, whereas WLI followed by BLI examination was conducted in the WLI group. The number, size, microstructure, and microvascular patterns of cardia polyps detected were recorded. Biopsy of the polyps was then performed. RESULTS: The detection rate of cardia polyps in the BLI group was higher than that in the WLI group (7.87% vs 4.22%, P = 0.018). The rate of overlooked lesions in the BLI group was lower than in the WLI group (0.64% vs 3.38%, P = 0.003). The diagnostic coincidence rate between magnifying BLI and histopathology was 88.16%. The sensitivity, specificity, positive predictive value and negative predictive value for the diagnosis of neoplastic lesions by magnifying endoscopy with BLI were 90.91%, 87.69%, 55.56%, and 98.28%, respectively. The most remarkable patterns for predicting inflammatory polyps were the prolonged and fine network patterns (sensitivity 71.43%, specificity 93.75%). Small round combined with honeycomb patterns were the most common among fundic gland polyps (sensitivity 80.00%, specificity 98.48%). Neoplastic lesions presented as villous or ridge-like combined with core vascular or unclear pattern for both microvascular and microstructure patterns. CONCLUSION: BLI is more effective than WLI in the detection and diagnosis of cardia polyps, and magnifying endoscopy with BLI may help diagnose such lesions.


Assuntos
Cárdia , Estudos de Viabilidade , Neoplasias Gástricas , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Cárdia/patologia , Cárdia/diagnóstico por imagem , Adulto , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/diagnóstico , Neoplasias Gástricas/patologia , Idoso , Pólipos/diagnóstico por imagem , Pólipos/diagnóstico , Gastroscopia/métodos , Sensibilidade e Especificidade , Valor Preditivo dos Testes , Lasers
15.
BMC Infect Dis ; 24(1): 485, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730327

RESUMO

BACKGROUND: Neurobrucellosis (NB) is a rare and serious complication of brucellosis. Its clinical manifestations vary, with no obvious specificity. At present, there is no clear clinical diagnosis or treatment for reference. In this study, we retrospectively analyzed the clinical data for 21 patients with NB to provide reference data for its further study. METHODS: We analyzed the epidemiological and clinical manifestations, laboratory tests, imaging examinations, cerebrospinal fluid, and treatment plans of 21 patients diagnosed with NB in the Department of Neurology, Xuanwu Hospital, Capital Medical University Beijing, China. RESULTS: The ages of the patients ranged from 15 to 60 years old (mean age 40.1 ± 13.33 years), the male: female ratio was 4.25:1. Thirteen patients had a history of animal (sheep, cattle) contact, three had no history of animal contact, and the contact status of four was unknown. Brucella can invade various systems of the body and show multi-system symptoms, the main general manifestations were fever (66.67%), fatigue (57.14%) and functional urination or defecation disturbance (42.86%). The main nervous system manifestations were limb weakness (52.38%) and hearing loss (47.62%).The main positive signs of the nervous system included positive pathological signs (71.43%), sensory abnormalities (52.38%), limb paralysis (42.86%). Nervous system lesions mainly included spinal cord damage (66.67%), cranial nerve involvement (61.90%), central demyelination (28.57%) and meningitis (28.57%). In patients with cranial nerve involvement, 69.23% of auditory nerve, 15.38% of optic nerve and 15.38% of oculomotor nerve were involved. The blood of eight patients was cultured for Brucella, and three (37.5%) cultures were positive and five (63.5%) negative. The cerebrospinal fluid (CSF) of eight patients was cultured for Brucella, and two (25.00%) cultures were positive and six (75.00%) negative. Nineteen of the patients underwent a serum agglutination test (SAT), 18 (94.74%) of whom were positive and one (5.26%) of whom were negative. A biochemical analysis of the CSF was performed in 21 patients, and the results were all abnormal. Nineteen patients underwent magnetic resonance imaging (MRI). Twenty-one patients were treated with doxycycline and/or rifampicin, combined with ceftriaxone, quinolone, aminoglycoside, or minocycline. After hospitalization, 15 patients improved (71.43%), two patients did not recover, and the status of four patients was unknown. CONCLUSIONS: The clinical manifestations, CSF parameters, and neurological imaging data for patients with NB show no significant specificity or correlations. When patients with unexplained neurological symptoms accompanied by fever, fatigue, and other systemic manifestations in a brucellosis epidemic area or with a history of contact with cattle, sheep, animals, or raw food are encountered in clinical practice, the possibility of NB should be considered. Treatment is based on the principles of an early, combined, and long course of treatment, and the general prognosis is good.


Assuntos
Antibacterianos , Brucelose , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Brucelose/tratamento farmacológico , Brucelose/microbiologia , Brucelose/líquido cefalorraquidiano , Brucelose/diagnóstico , Brucelose/epidemiologia , Adulto , Antibacterianos/uso terapêutico , Estudos Retrospectivos , Adolescente , Adulto Jovem , China/epidemiologia , Resultado do Tratamento , Brucella/isolamento & purificação , Animais
16.
Sci Rep ; 14(1): 12430, 2024 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-38816541

RESUMO

Dietary trans 10, cis 12-conjugated linoleic acid (t10c12-CLA) is a potential candidate in anti-obesity trials. A transgenic mouse was previously successfully established to determine the anti-obesity properties of t10c12-CLA in male mice that could produce endogenous t10c12-CLA. To test whether there is a different impact of t10c12-CLA on lipid metabolism in both sexes, this study investigated the adiposity and metabolic profiles of female Pai mice that exhibited a dose-dependent expression of foreign Pai gene and a shift of t10c12-CLA content in tested tissues. Compared to their gender-match wild-type littermates, Pai mice had no fat reduction but exhibited enhanced lipolysis and thermogenesis by phosphorylated hormone-sensitive lipase and up-regulating uncoupling proteins in brown adipose tissue. Simultaneously, Pai mice showed hepatic steatosis and hypertriglyceridemia by decreasing gene expression involved in lipid and glucose metabolism. Further investigations revealed that t10c10-CLA induced excessive prostaglandin E2, adrenaline, corticosterone, glucagon and inflammatory factors in a dose-dependent manner, resulting in less heat release and oxygen consumption in Pai mice. Moreover, fibroblast growth factor 21 overproduction only in monoallelic Pai/wt mice indicates that it was sensitive to low doses of t10c12-CLA. These results suggest that chronic t10c12-CLA has system-wide effects on female health via synergistic actions of various hormones.


Assuntos
Corticosterona , Dinoprostona , Epinefrina , Fatores de Crescimento de Fibroblastos , Glucagon , Ácidos Linoleicos Conjugados , Camundongos Transgênicos , Animais , Feminino , Fatores de Crescimento de Fibroblastos/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Camundongos , Ácidos Linoleicos Conjugados/farmacologia , Ácidos Linoleicos Conjugados/metabolismo , Corticosterona/metabolismo , Dinoprostona/metabolismo , Glucagon/metabolismo , Epinefrina/metabolismo , Termogênese/efeitos dos fármacos , Termogênese/genética , Masculino , Metabolismo dos Lipídeos/efeitos dos fármacos , Tecido Adiposo Marrom/metabolismo , Tecido Adiposo Marrom/efeitos dos fármacos , Fígado Gorduroso/metabolismo , Fígado Gorduroso/genética , Lipólise/efeitos dos fármacos , Hipertrigliceridemia/metabolismo , Hipertrigliceridemia/genética , Adiposidade/efeitos dos fármacos
17.
J Chin Med Assoc ; 87(6): 581-589, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38651895

RESUMO

BACKGROUND: Metastasis-associated lung adenocarcinoma transcript 1 ( MALAT1 ) plays a critical role in the pathophysiology of diabetes-related complications. However, whether macrophage-derived MALAT1 affects autophagic activity under hyperglycemic conditions is unclear. Therefore, we investigated the molecular regulatory mechanisms of macrophage-derived MALAT1 and autophagy under hyperglycemic conditions. METHODS: Hyperglycemia was induced by culturing macrophages in 25 mM glucose for 1 hour. Exosomes were extracted from the culture media. A rat model of carotid artery balloon injury was established to assess the effect of MALAT1 on vascular injury. Reverse transcription, real-time quantitative polymerase chain reaction, western blotting, immunohistochemical staining, and luciferase activity assays were performed. RESULTS: Stimulation with high levels of glucose significantly enhanced MALAT1 expression in macrophage-derived exosomes. MALAT1 inhibited miR-204-5p expression in macrophage-derived exosomes under hyperglycemic conditions. siRNA-induced silencing of MALAT1 significantly reversed macrophage-derived exosome-induced miR-204-5p expression. Hyperglycemic treatment caused a significant, exosome-induced increase in the expression of the autophagy marker LC3B in macrophages. Silencing MALAT1 and overexpression of miR-204-5p significantly decreased LC3B expression induced by macrophage-derived exosomes. Overexpression of miR-204-5p significantly reduced LC3B luciferase activity induced by macrophage-derived exosomes. Balloon injury to the carotid artery in rats significantly enhanced MALAT1 and LC3B expression, and significantly reduced miR-204-5p expression in carotid artery tissue. Silencing MALAT1 significantly reversed miR-204-5p expression in carotid artery tissue after balloon injury. MALAT1 silencing or miR-204-5p overexpression significantly reduced LC3B expression after balloon injury. CONCLUSION: This study demonstrated that hyperglycemia upregulates MALAT1 . MALAT1 suppresses miR-204-5p expression and counteracts the inhibitory effect of miR-204-5p on LC3B expression in macrophages to promote vascular disease.


Assuntos
Regulação para Baixo , Exossomos , Glucose , Macrófagos , MicroRNAs , RNA Longo não Codificante , Regulação para Cima , Animais , Masculino , Camundongos , Ratos , Autofagia/efeitos dos fármacos , Células Cultivadas , Exossomos/metabolismo , MicroRNAs/fisiologia , MicroRNAs/genética , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Ratos Sprague-Dawley , RNA Longo não Codificante/fisiologia , RNA Longo não Codificante/genética
18.
Virology ; 595: 110097, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38685171

RESUMO

Current influenza vaccine is not effective in providing cross-protection against variants. We evaluated the immunogenicity and efficacy of multi-subtype neuraminidase (NA) and M2 ectodomain virus-like particle (m-cNA-M2e VLP) and chimeric M2e-H3 stalk protein vaccines (M2e-H3 stalk) in ferrets. Our results showed that ferrets with recombinant m-cNA-M2e VLP or M2e-H3 stalk vaccination induced multi-vaccine antigen specific IgG antibodies (M2e, H3 stalk, NA), NA inhibition, antibody-secreting cells, and IFN-γ secreting cell responses. Ferrets immunized with either m-cNA-M2e VLP or M2e-H3 stalk vaccine were protected from H1N1 and H3N2 influenza viruses by lowering viral titers in nasal washes, trachea, and lungs after challenge. Vaccinated ferret antisera conferred broad humoral immunity in naïve mice. Our findings provide evidence that immunity to M2e and HA-stalk or M2e plus multi-subtype NA proteins induces cross-protection in ferrets.


Assuntos
Anticorpos Antivirais , Proteção Cruzada , Furões , Vírus da Influenza A Subtipo H1N1 , Vírus da Influenza A Subtipo H3N2 , Vacinas contra Influenza , Neuraminidase , Infecções por Orthomyxoviridae , Vacinas de Partículas Semelhantes a Vírus , Animais , Vacinas contra Influenza/imunologia , Vacinas contra Influenza/administração & dosagem , Proteção Cruzada/imunologia , Anticorpos Antivirais/imunologia , Neuraminidase/imunologia , Neuraminidase/genética , Infecções por Orthomyxoviridae/prevenção & controle , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/virologia , Vírus da Influenza A Subtipo H3N2/imunologia , Vírus da Influenza A Subtipo H3N2/genética , Vírus da Influenza A Subtipo H1N1/imunologia , Vacinas de Partículas Semelhantes a Vírus/imunologia , Vacinas de Partículas Semelhantes a Vírus/administração & dosagem , Camundongos , Proteínas da Matriz Viral/imunologia , Proteínas da Matriz Viral/genética , Feminino , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Proteínas Viroporinas , Proteínas Virais
19.
J Asian Nat Prod Res ; 26(8): 930-944, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38598409

RESUMO

A sensitive UPLC-HRMS method was developed and validated for simultaneous quantification of four active flavonoids from Chimonanthus nitens Leaf Granules (CNLG) in biological matrix. The method was utilized in pharmacokinetic study of the four flavonoids in rats as well as other evaluation assays in vitro. It was revealed that rutin, nicotiflorin, and astragalin had poor oral bioavailability in rats possibly due to low intestinal permeability and metabolism in intestinal flora. Kaempferol underwent rapid glucuronidation and sulphation in rat plasma with medium permeability coefficient. The results provided valuable data for future research and development of CNLG flavonoids.


Assuntos
Flavonoides , Quempferóis , Folhas de Planta , Animais , Flavonoides/farmacocinética , Flavonoides/química , Folhas de Planta/química , Ratos , Quempferóis/farmacocinética , Quempferóis/química , Estrutura Molecular , Masculino , Rutina/farmacocinética , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacocinética , Ratos Sprague-Dawley , Calycanthaceae/química , Cromatografia Líquida/métodos , Disponibilidade Biológica , Espectrometria de Massas/métodos , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massa com Cromatografia Líquida
20.
Pestic Biochem Physiol ; 200: 105816, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38582574

RESUMO

The melon fly Zeugodacus cucurbitae Coquillett (Diptera: Tephritidae) is an agricultural quarantine pest threatening fruit and vegetable production. Heat shock cognate 70 (Hsc70), which is a homolog of the heat shock protein 70 (Hsp70), was first discovered in mice testes and plays an important role in spermatogenesis. In this study, we identified and cloned five Hsc70 genes from melon fly, namely ZcHsc70_1/2/3/4/5. Phylogenetic analysis showed that these proteins are closely related to Hsc70s from other Diptera insects. Spatiotemporal expression analysis showed that ZcHsc70_1 and ZcHsc70_2 are highly expressed in Z. cucurbitae testes. Fluorescence in situ hybridization further demonstrated that ZcHsc70_1 and ZcHsc70_2 are expressed in the transformation and maturation regions of testes, respectively. Moreover, RNA interference-based suppression of ZcHsc70_1 or ZcHsc70_2 resulted in a significant decrease of 74.61% and 63.28% in egg hatchability, respectively. Suppression of ZcHsc70_1 expression delayed the transformation of sperm cells to mature sperms. Meanwhile, suppression of ZcHsc70_2 expression decreased both sperm cells and mature sperms by inhibiting the meiosis of spermatocytes. Our findings show that ZcHsc70_1/2 regulates spermatogenesis and further affects the male fertility in the melon fly, showing potential as targets for pest control in sterile insect technique by genetic manipulation of males.


Assuntos
Sementes , Tephritidae , Masculino , Animais , Camundongos , Filogenia , Hibridização in Situ Fluorescente , Tephritidae/genética , Controle de Insetos/métodos , Espermatogênese/genética , Fertilidade/genética , Resposta ao Choque Térmico
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