RESUMEN
Grass carp reovirus (GCRV), particularly the highly prevalent type II GCRV (GCRV-II), causes huge losses in the aquaculture industry. However, little is known about the mechanisms by which GCRV-II invades grass carp and further disseminates among tissues. In the present study, monocytes/macrophages (Mo/Mφs) were isolated from the peripheral blood of grass carp and infected with GCRV-II. The results of indirect immunofluorescent microscopy, transmission electron microscopy, real-time quantitative RT-PCR (qRT-PCR), western blot (WB), and flow cytometry analysis collectively demonstrated that GCRV-II invaded Mo/Mφs and replicated in them. Additionally, we observed that GCRV-II induced different types (M1 and M2) of polarization of Mo/Mφs in multiple tissues, especially in the brain, head kidney, and intestine. To assess the impact of different types of polarization on GCRV-II replication, we recombinantly expressed and purified the intact cytokines CiIFN-γ2, CiIL-4/13A, and CiIL-4/13B and successfully induced M1 and M2 type polarization of macrophages using these cytokines through in vitro experiments. qRT-PCR, WB, and flow cytometry analyses showed that M2 macrophages had higher susceptibility to GCRV-II infection than other types of Mo/Mφs. In addition, we found GCRV-II induced apoptosis of Mo/Mφs to facilitate virus replication and dissemination and also detected the presence of GCRV-II virus in plasma. Collectively, our findings indicated that GCRV-II could invade immune cells Mo/Mφs and induce apoptosis and polarization of Mo/Mφs for efficient infection and dissemination, emphasizing the crucial role of Mo/Mφs as a vector for GCRV-II infection.IMPORTANCEType II grass carp reovirus (GCRV) is a prevalent viral strain and causes huge losses in aquaculture. However, the related dissemination pathway and mechanism remain largely unclear. Here, our study focused on phagocytic immune cells, monocytes/macrophages (Mo/Mφs) in blood and tissues, and explored whether GCRV-II can invade Mo/Mφs and replicate and disseminate via Mo/Mφs with their differentiated type M1 and M2 macrophages. Our findings demonstrated that GCRV-II infected Mo/Mφs and replicated in them. Furthermore, GCRV-II infection induces an increased number of M1 and M2 macrophages in grass carp tissues and a higher viral load in M2 macrophages. Furthermore, GCRV-II induced Mo/Mφs apoptosis to release viruses, eventually infecting more cells. Our study identified Mo/Mφs as crucial components in the pathway of GCRV-II dissemination and provides a solid foundation for the development of treatment strategies for GCRV-II infection.
Asunto(s)
Carpas , Enfermedades de los Peces , Orthoreovirus , Infecciones por Reoviridae , Animales , Apoptosis , Citocinas , Enfermedades de los Peces/metabolismo , Enfermedades de los Peces/patología , Enfermedades de los Peces/virología , Macrófagos/metabolismo , Macrófagos/patología , Macrófagos/virología , Monocitos/metabolismo , Infecciones por Reoviridae/metabolismo , Infecciones por Reoviridae/patología , Infecciones por Reoviridae/veterinaria , Replicación ViralRESUMEN
BACKGROUND & AIMS: HBV expresses more than 10 spliced RNAs from the viral pregenomic RNA, but their functions remain elusive and controversial. To address the function of HBV spliced RNAs, we generated splicing-deficient HBV mutants and conducted experiments to assess the impact of these mutants on HBV infection. METHODS: HepG2-NTCP cells, human hepatocyte chimeric FRG mice (hu-FRG mice), and serum from patients with chronic hepatitis B were used for experiments on HBV infection. Additionally, SHifter assays and cryo-electron microscopy were performed. RESULTS: We found the infectivity of splicing-deficient HBV was decreased 100-1,000-fold compared with that of wild-type HBV in hu-FRG mice. Another mutant, A487C, which loses the most abundant spliced RNA (SP1), also exhibits severely impaired infectivity. SP1 hypothetically encodes a novel protein HBcSP1 (HBc-Cys) that lacks the C-terminal cysteine from full-length HBc. In the SHifter assay, HBcSP1 was detected in wild-type viral particles at a ratio of about 20-100% vs. conventional HBc, as well as in the serum of patients with chronic hepatitis B, but not in A487C particles. When infection was conducted with a shorter incubation time of 4-8 h at lower PEG concentrations in HepG2-NTCP cells, the entry of the A487C mutant was significantly slower. SP1 cDNA complementation of the A487C mutant succeeded in rescuing its infectivity in hu-FRG mice and HepG2-NTCP cells. Moreover, cryo-electron microscopy revealed a disulfide bond between HBc cysteine 183 and 48 in the HBc intradimer of the A487C capsid, leading to a locked conformation that disfavored viral entry in contrast to the wild-type capsid. CONCLUSIONS: Prior studies unveiled the potential integration of the HBc-Cys protein into the HBV capsid. We confirmed the proposal and validated its identity and function during infection. IMPACT AND IMPLICATIONS: HBV SP1 RNA encodes a novel HBc protein (HBcSP1) that lacks the C-terminal cysteine from conventional HBc (HBc-Cys). HBcSP1 was detected in cell culture-derived HBV and confirmed in patients with chronic infection by both immunological and chemical modification assays at 10-50% of capsid. The splicing-deficient mutant HBV (A487C) impaired infectivity in human hepatocyte chimeric mice and viral entry in the HepG2-NTCP cell line. Furthermore, these deficiencies of the splicing-deficient mutant could be rescued by complementation with the SP1-encoded protein HBcSP1. We confirmed and validated the identity and function of HBcSP1 during infection, building on the current model of HBV particles.
Asunto(s)
Virus de la Hepatitis B , Hepatitis B Crónica , Humanos , Animales , Virus de la Hepatitis B/genética , Ratones , Células Hep G2 , Hepatitis B Crónica/virología , Empalme del ARN , Mutación , ARN Viral/genética , ARN Viral/metabolismo , Microscopía por CrioelectrónRESUMEN
BACKGROUND: NADPH oxidase (NOX), a primary source of endothelial reactive oxygen species (ROS), is considered a key event in disrupting the integrity of the blood-retinal barrier. Abnormalities in neurovascular-coupled immune signaling herald the loss of ganglion cells in glaucoma. Persistent microglia-driven inflammation and cellular innate immune system dysregulation often lead to deteriorating retinal degeneration. However, the crosstalk between NOX and the retinal immune environment remains unresolved. Here, we investigate the interaction between oxidative stress and neuroinflammation in glaucoma by genetic defects of NOX2 or its regulation via gp91ds-tat. METHODS: Ex vivo cultures of retinal explants from wildtype C57BL/6J and Nox2 -/- mice were subjected to normal and high hydrostatic pressure (Pressure 60 mmHg) for 24 h. In vivo, high intraocular pressure (H-IOP) was induced in C57BL/6J mice for two weeks. Both Pressure 60 mmHg retinas and H-IOP mice were treated with either gp91ds-tat (a NOX2-specific inhibitor). Proteomic analysis was performed on control, H-IOP, and treatment with gp91ds-tat retinas to identify differentially expressed proteins (DEPs). The study also evaluated various glaucoma phenotypes, including IOP, retinal ganglion cell (RGC) functionality, and optic nerve (ON) degeneration. The superoxide (O2-) levels assay, blood-retinal barrier degradation, gliosis, neuroinflammation, enzyme-linked immunosorbent assay (ELISA), western blotting, and quantitative PCR were performed in this study. RESULTS: We found that NOX2-specific deletion or activity inhibition effectively attenuated retinal oxidative stress, immune dysregulation, the internal blood-retinal barrier (iBRB) injury, neurovascular unit (NVU) dysfunction, RGC loss, and ON axonal degeneration following H-IOP. Mechanistically, we unveiled for the first time that NOX2-dependent ROS-driven pro-inflammatory signaling, where NOX2/ROS induces endothelium-derived endothelin-1 (ET-1) overexpression, which activates the ERK1/2 signaling pathway and mediates the shift of microglia activation to a pro-inflammatory M1 phenotype, thereby triggering a neuroinflammatory outburst. CONCLUSIONS: Collectively, we demonstrate for the first time that NOX2 deletion or gp91ds-tat inhibition attenuates iBRB injury and NVU dysfunction to rescue glaucomatous RGC loss and ON axon degeneration, which is associated with inhibition of the ET-1/ERK1/2-transduced shift of microglial cell activation toward a pro-inflammatory M1 phenotype, highlighting NOX2 as a potential target for novel neuroprotective therapies in glaucoma management.
Asunto(s)
Barrera Hematorretinal , Presión Intraocular , Ratones Endogámicos C57BL , NADPH Oxidasa 2 , Enfermedades Neuroinflamatorias , Animales , NADPH Oxidasa 2/metabolismo , NADPH Oxidasa 2/genética , Ratones , Barrera Hematorretinal/patología , Barrera Hematorretinal/metabolismo , Presión Intraocular/fisiología , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/patología , Ratones Noqueados , Proliferación Celular/fisiología , Sistema de Señalización de MAP Quinasas/fisiología , Neuroglía/metabolismo , Neuroglía/patología , Hipertensión Ocular/patología , Hipertensión Ocular/metabolismo , Glaucoma/patología , Glaucoma/metabolismo , Estrés Oxidativo/fisiologíaRESUMEN
Salt and drought stresses are major factors limiting soybean (Glycine max [L.] Merr.) growth and development; thus, improving soybean stress tolerance is critical. In this study, both salt stress and drought stress induced mRNA levels of CONSTANS-like 1a (GmCOL1a) and stabilized the GmCOL1a protein. Transgenic 35S:GmCOL1a soybean plants exhibited enhanced salt and drought tolerance, with higher relative water content in leaves, greater proline content, lower malondialdehyde (MDA) content, and less reactive oxygen species (ROS) production compared with wild-type plants; the GmCOL1a knockout co-9 mutant showed opposite phenotypes. In addition, GmCOL1a promoted the expression of genes related to salt tolerance, effectively reducing the Na+/K+ ratio in soybean plants, especially in stems and leaves of 35S:GmCOL1a soybean. Chromatin immunoprecipitation sequencing (ChIP-seq) analysis identified two potential direct targets of GmCOL1a, late embryogenesis abundant (GmLEA) and Δ1-pyrroline-5-carboxylate synthetase (GmP5CS) genes, which were verified by chromatin immunoprecipitation quantitative polymerase chain reaction (ChIP-qPCR), electrophoretic mobility shift assay (EMSA), and transient transcriptional activation assays. GmCOL1a bound directly to the Myc(bHLH)-binding and Che-binding motifs of GmLEA and GmP5CS promoters to stimulate mRNA expression. Analysis of transgenic hairy-root GmP5CS:GmP5CS soybean plants in wild type, co-9, and 35S:GmCOL1a backgrounds further revealed that GmCOL1a enhances salt and drought tolerance by promoting GmP5CS protein accumulation in transgenic soybean hairy roots. Therefore, we demonstrate that GmCOL1a plays an important role in tolerance to abiotic stress in soybean.
Asunto(s)
Resistencia a la Sequía , Glycine max , Glycine max/metabolismo , Proteínas de Plantas/metabolismo , Estrés Salino , Tolerancia a la Sal/genética , Estrés Fisiológico/genética , Sequías , Plantas Modificadas Genéticamente/metabolismo , Regulación de la Expresión Génica de las PlantasRESUMEN
Obesity is a significant health concern that leads to impaired vascular function and subsequent abnormalities in various organs. The impact of obesity on ocular blood vessels, however, remains largely unclear. In this study, we examined the hypothesis that obesity induced by high-fat diet produces vascular endothelial dysfunction in the ophthalmic artery. Mice were subjected to a high-fat diet for 20 weeks, while age-matched controls were maintained on a standard diet. Reactivity of isolated ophthalmic artery segments was assessed in vitro. Reactive oxygen species (ROS) were quantified in cryosections by dihydroethidium (DHE) staining. Redox gene expression was determined in ophthalmic artery explants by real-time PCR. Furthermore, the expression of nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), the receptor for advanced glycation end products (RAGE), and of the lectin-like oxidized low-density-lipoprotein receptor-1 (LOX-1) was determined in cryosections using immunofluorescence microscopy. Ophthalmic artery segments from mice on a high-fat diet exhibited impaired vasodilation responses to the endothelium-dependent vasodilator acetylcholine, while endothelium-independent responses to nitroprusside remained preserved. DHE staining intensity in the vascular wall was notably stronger in mice on a high-fat diet. Messenger RNA expression for NOX2 was elevated in the ophthalmic artery of mice subjected to high fat diet. Likewise, immunostainings revealed increased expression of NOX2 and of RAGE, but not of LOX-1. These findings suggest that a high-fat diet triggers endothelial dysfunction by inducing oxidative stress in the ophthalmic artery via involvement of RAGE and NOX2.
Asunto(s)
Dieta Alta en Grasa , Arteria Oftálmica , Enfermedades Vasculares , Animales , Ratones , Dieta Alta en Grasa/efectos adversos , Endotelio Vascular/metabolismo , Obesidad , Arteria Oftálmica/metabolismo , Estrés Oxidativo/fisiología , Especies Reactivas de Oxígeno/metabolismo , Receptores Depuradores de Clase E/genética , Receptores Depuradores de Clase E/metabolismo , Enfermedades Vasculares/metabolismo , VasodilataciónRESUMEN
OBJECTIVES: Primary Sjögren's syndrome (pSS) is an inflammatory systemic autoimmune disease, while the role and mechanisms of pyroptosis in pSS remain largely undefined. METHODS: Pyroptosis-related genes and gene expression data were obtained from the Molecular Signatures Database and NCBI GEO databases. Differentially expressed genes (DEGs) and pyroptosis-related hub genes were identified by R software. Functional enrichment analyses were conducted using the "ClusterProfiler" R package and WebGestalt7. CIBERSORTx was used to calculate the correlations between immune cells and pyroptosis. Subsequently, histological staining was performed on salivary gland samples from non-pSS and pSS patients to identify the expression of pyroptosis-related genes. Immunofluorescence double staining was conducted to validate the correlation between immune cells and pyroptosis. RESULTS: A total of 1494 DEGs were identified between eight pSS samples and 10 healthy volunteer samples. Five pyroptosis-related hub genes (AIM2, CASP1, CASP3, IL6, TNF) were recognised. DEGs were mostly enriched in immunity-related terms and several immune cells were associated with the hub genes in pSS. Among them, delta gamma T cell was significantly positively correlated with CASP3. Finally, the protein levels of these hub genes were validated to be elevated in the labial minor salivary gland biopsies of pSS patients compared to those of healthy volunteers using immunohistochemical staining. Immunofluorescence double staining further showed that IL-6, AIM2, CASP1and CASP3 were related to delta gamma T cells, and TNF was related to dendritic cells. CONCLUSIONS: This study uncovered a significant interaction between pyroptosis and the immune microenvironment in pSS patients. Besides, we identified five pyroptosis-related hub genes that might play a role in the pathogenesis of pSS. These findings could offer valuable insights for the development of novel treatment strategies for pSS.
RESUMEN
BACKGROUND: Central pancreatectomy is a surgical procedure for benign and low-grade malignant tumors which located in the neck and proximal body of the pancreas that facilitates the preservation of pancreatic endocrine and exocrine functions but has a high morbidity rate, especially postoperative pancreatic fistula (POPF). The aim of this systematic review and meta-analysis was to evaluate the safety and effectiveness between minimally invasive central pancreatectomy (MICP) and open central pancreatectomy (OCP) basing on perioperative outcomes. METHODS: An extensive literature search to compare MICP and OCP was conducted from October 2003 to October 2023 on PubMed, Medline, Embase, Web of Science, and the Cochrane Library. Fixed-effect models or random effects were selected based on heterogeneity, and pooled odds ratios (ORs) or mean differences (MDs) with 95% confidence intervals (CIs) were calculated. RESULTS: A total of 10 studies with a total of 510 patients were included. There was no significant difference in POPF between MICP and OCP (OR = 0.95; 95% CI [0.64, 1.43]; P = 0.82), whereas intraoperative blood loss (MD = - 125.13; 95% CI [- 194.77, -55.49]; P < 0.001) and length of hospital stay (MD = - 2.86; 95% CI [- 5.00, - 0.72]; P = 0.009) were in favor of MICP compared to OCP, and there was a strong trend toward a lower intraoperative transfusion rate in MICP than in OCP (MD = 0.34; 95% CI [0.11, 1.00]; P = 0.05). There was no significant difference in other outcomes between the two groups. CONCLUSION: MICP was as safe and effective as OCP and had less intraoperative blood loss and a shorter length of hospital stay. However, further studies are needed to confirm the results.
Asunto(s)
Pancreatectomía , Neoplasias Pancreáticas , Complicaciones Posoperatorias , Humanos , Pancreatectomía/métodos , Pancreatectomía/efectos adversos , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Neoplasias Pancreáticas/cirugía , Fístula Pancreática/etiología , Fístula Pancreática/prevención & control , Fístula Pancreática/epidemiología , Tiempo de Internación/estadística & datos numéricos , Resultado del Tratamiento , Pérdida de Sangre Quirúrgica/estadística & datos numéricos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/efectos adversos , Laparoscopía/métodosRESUMEN
DNA methylation directed by 24-nucleotide (nt) small interfering RNAs (siRNAs) plays critical roles in gene regulation and transposon silencing in Arabidopsis. 24-nt siRNAs are known to be processed from double-stranded RNAs by Dicer-like 3 (DCL3) and loaded into the effector Argonaute 4 (AGO4). Here we report a distinct class of siRNAs independent of DCLs (sidRNAs). sidRNAs are present as ladders of â¼ 20-60 nt in length, often having the same 5' ends but differing in 3' ends by 1-nt steps. We further show that sidRNAs are associated with AGO4 and capable of directing DNA methylation. Finally we show that sidRNA production depends on distributive 3'-5' exonucleases. Our findings suggest an alternative route for siRNA biogenesis. Precursor transcripts are bound by AGO4 and subsequently subjected to 3'-5' exonucleolytic trimming for maturation. We propose that sidRNAs generated through this route are the initial triggers of de novo DNA methylation.
Asunto(s)
Proteínas de Arabidopsis/metabolismo , Arabidopsis/genética , Metilación de ADN , ARN Interferente Pequeño/biosíntesis , Proteínas de Arabidopsis/genética , Proteínas Argonautas/metabolismo , Secuencia de Bases , Genoma de Planta , Datos de Secuencia Molecular , Mutación/genética , ARN de Planta/genética , ARN Polimerasa Dependiente del ARN/genética , Plantones/genéticaRESUMEN
In this work, we report on an electrochemical method for the signal-on detection of caspase-3 and the evaluation of apoptosis based on the biotinylation reaction and the signal amplification of methylene blue (MB)-loaded metal-organic frameworks (MOFs). Zr-based UiO-66-NH2 MOFs were used as the nanocarriers to load electroactive MB molecules. Recombinant hexahistidine (His6)-tagged streptavidin (rSA) was attached to the MOFs through the coordination interaction between the His6 tag in rSA and the metal ions on the surface of the MOFs. The acetylated peptide substrate Ac-GDEVDGGGPPPPC was immobilized on the gold electrode. In the presence of caspase-3, the peptide was specifically cleaved, leading to the release of the Ac-GDEVD sequence. A N-terminal amine group was generated and then biotinylated in the presence of biotin-NHS. Based on the strong interaction between rSA and biotin, rSA@MOF@MB was captured by the biotinylated peptide-modified electrode, producing a significantly amplified electrochemical signal. Caspase-3 was sensitively determined with a linear range from 0.1 to 25 pg/mL and a limit of detection down to 0.04 pg/mL. Further, the active caspase-3 in apoptosis inducer-treated HeLa cells was further quantified by this method. The proposed signal-on biosensor is compatible with the complex biological samples and shows great potential for apoptosis-related diagnosis and the screening of caspase-targeting drugs.
Asunto(s)
Técnicas Biosensibles , Caspasa 3 , Estructuras Metalorgánicas , Azul de Metileno , Estructuras Metalorgánicas/química , Azul de Metileno/química , Humanos , Caspasa 3/metabolismo , Células HeLa , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Apoptosis , Estreptavidina/química , Biotinilación , Electrodos , Límite de Detección , Circonio/química , Ácidos FtálicosRESUMEN
Enzyme-linked electrochemical immunosensors have attracted considerable attention for the sensitive and selective detection of various targets in clinical diagnosis, food quality control, and environmental analysis. In order to improve the performances of conventional immunoassays, significant efforts have been made to couple enzyme-linked or nanozyme-based catalysis and redox cycling for signal amplification. The current review summarizes the recent advances in the development of enzyme- or nanozyme-based electrochemical immunosensors with redox cycling for signal amplification. The special features of redox cycling reactions and their synergistic functions in signal amplification are discussed. Additionally, the current challenges and future directions of enzyme- or nanozyme-based electrochemical immunosensors with redox cycling are addressed.
Asunto(s)
Técnicas Biosensibles , Técnicas Electroquímicas , Oxidación-Reducción , Técnicas Biosensibles/métodos , Técnicas Electroquímicas/métodos , Inmunoensayo/métodos , Catálisis , Humanos , Enzimas/metabolismo , Enzimas/químicaRESUMEN
BACKGROUND: Pile fermentation is one of the key steps in developing the Liupao tea (LBT) quality and unique characteristics. The complex biochemical profile of LBT results from microorganisms present during the pile-fermentation process. However, the critical underlying microorganisms and the marker compounds still need to be determined. RESULTS: Staphylococcus, Brevibacterium, Kocuria, Aspergillus, and Blastobotrys were the common dominant microorganisms at the end of the pile fermentation of LBT. Staphylococcus, Aspergillus, Blastobotrys, and nine other genera carried by raw tea are the core microorganisms in the LBT during pile fermentation. A total of 29 critical compounds contributed to the metabolic changes caused by the processing of LBT. Of these, gallic acid, adenine, hypoxanthine, uridine, betaine, 3,4-dihydroxybenzaldehyde, and α-linolenic acid could be characterized as potential marker compounds. Correlation analysis showed that the core microorganisms, including Sphingomonas, Staphylococcus, Kocuria, Aureobasidium, Blastobotrys, Debaryomyce, and Trichomonascus, were closely related to major chemical components and differential compounds. Moreover, the mutually promoting Staphylococcus, Kocuria, Blastobotrys, and Trichomonascus were correlated with the enrichment of marker compounds. Integrated molecular networking and metabolic pathways revealed relevant compounds and enzymes that possibly affect the enrichment of marker compounds. CONCLUSION: This study analyzed the LBT fermentation samples by omics analysis to reveal the stable microbial community structure, critical microorganisms, and markers compounds affecting the quality of LBT, which contributes to a better understanding of pile fermentation of LBT and the fermentation theory of dark tea. © 2023 Society of Chemical Industry.
Asunto(s)
Microbiota , Saccharomycetales , Fermentación , Té/química , Aspergillus/genética , Aspergillus/metabolismo , Saccharomycetales/metabolismoRESUMEN
BACKGROUND: The adhesion of probiotics to the intestine is crucial for their probiotic function. In previous studies, Tremella polysaccharides (TPS) (with sodium casein) have shown the potential to encapsulate probiotics and protect them in a simulated gastrointestinal tract. This study explored the effect of TPS (with sodium casein) on the adhesion of probiotics. RESULTS: Lactobacillus plantarum was coated with TPS and sodium casein in different proportions, and was freeze-dried. The rheological properties of the mixture of probiotics powder and mucin solution were determined by static and dynamic rheological analysis. Aqueous solutions of probiotic powder and mucin mixture exhibited pseudoplastic fluid rheological properties. The higher the proportion of TPS content, the higher the apparent viscosity and yield stress. The mixed bacterial powder and mucin fluid displayed thixotropy and was in accordance with the Herschel-Bulkley model. The TPS increased the bio-adhesive force of the probiotic powder and mucin. When using TPS as the only carbon source, the adhesion of L. plantarum to Caco-2 cells increased by 228% in comparison with glucose in vitro. Twelve adhesive proteins were also detected in the whole-cell proteome of L. plantarum. Among them, ten adhesive proteins occurred abundantly when grown with TPS as a carbon source. CONCLUSION: Tremella polysaccharides therefore possess probiotic properties and can promote the intestinal adhesion of L. plantarum. © 2024 Society of Chemical Industry.
Asunto(s)
Adhesión Bacteriana , Lactobacillus plantarum , Polisacáridos , Probióticos , Lactobacillus plantarum/química , Lactobacillus plantarum/metabolismo , Probióticos/química , Humanos , Células CACO-2 , Adhesión Bacteriana/efectos de los fármacos , Polisacáridos/química , Polisacáridos/farmacología , Basidiomycota/química , Basidiomycota/metabolismo , Intestinos/microbiología , Reología , Viscosidad , Mucinas/química , Mucinas/metabolismoRESUMEN
Organic frameworks face a trade-off between the framework stability and the bond dynamics, which necessitates the development of innovative linkages that can generate stable frameworks without hindering efficient synthesis. Although iodine(I)-based halogen-bonded organic frameworks (XOFs) have been developed, constructing XOFs based on bromine(I) is desirable yet challenging due to the high sensitivity of bromine(I) species. In this work, we present the inaugural construction of stable bromine(I)-bridged two-dimensional (2D) halogen-bonded organic frameworks, XOF(Br)-TPy-BF4/OTf, based on sensitive [Nâ â â Brâ â â N]+ halogen bonds. The formation of XOF(Br)-TPy-BF4/OTf was monitored by 1H NMR, XPS, IR, SEM, TEM, HR-TEM, SEAD. Their framework structures were established by the results from PXRD, theoretical simulations and SAXS. More importantly, XOF(Br) displayed excellent chemical and thermal stabilities. They exhibited stable two-dimensional framework structures in various organic solvents and aqueous media, even over a wide pH range (pH 3-12), while the corresponding model compounds BrPy2BF4/OTf decomposed quickly even in the presence of minimal water. Furthermore, the influence of the counterions were investigated by replacing BF4 with OTf, which improved the stability of XOF(Br). This characteristic enabled XOF(Br) to serve as an efficient oxidizing reagent in aqueous environments, in contrast with the sensitivity of BrPy2BF4/OTf, which performed well only in organic media. This study not only deepens our fundamental understanding of organic frameworks but also opens new avenues for the development and application of multifunctional XOFs.
RESUMEN
Alcohol consumption is a leading risk factor and increases the risk of liver diseases, cancers, tuberculosis, and injuries. The relationship between alcohol use and cardiovascular risk is complex. While it is well established that heavy alcohol use and binge drinking harm cardiovascular health, the effect of light-to-moderate alcohol consumption remains controversial. Observational studies have repeatedly confirmed the U- or J-shaped relationship between alcohol consumption and cardiovascular disease risk, with the lowest risk observed in the light-to-moderate drinking group. However, the protective effect of low-level alcohol has been challenged by recent genetic epidemiological studies with Mendelian randomization. Such studies have their own limitations, and the application of this methodology in studying alcohol has been questioned. Results from the latest Global Burden of Diseases, Injuries, and Risk Factors Study suggest that the impact of alcohol consumption on health depends on the age structure and the distribution of disease burden and underlying causes in a given population. For young adults, even small amounts of alcohol cause heath loss. For older adults facing a high burden of cardiovascular diseases, light-to-moderate alcohol consumption may improve cardiovascular health outcomes. Mechanistically, all types of alcoholic beverages, including wine, spirits, and beer, have been shown to increase the levels of high-density lipoprotein cholesterol and adiponectin, and reduce the level of fibrinogen. Nonalcoholic components of wine, especially polyphenolic compounds like resveratrol, may additionally enhance endothelial nitric oxide production, and provide antioxidant and anti-inflammatory effects.
Asunto(s)
Enfermedades Cardiovasculares , Vino , Adulto Joven , Humanos , Anciano , Etanol , Consumo de Bebidas Alcohólicas/efectos adversos , Enfermedades Cardiovasculares/etiología , Vino/análisis , Factores de RiesgoRESUMEN
Hypertensive disorders of pregnancy are complications that can lead to maternal and infant mortality and morbidity. Hypertensive disorders of pregnancy are generally defined as hypertension and may be accompanied by other end organ damages including proteinuria, maternal organ disturbances including renal insufficiency, neurological complications, thrombocytopenia, impaired liver function, or uteroplacental dysfunction such as fetal growth restriction and stillbirth. Although the causes of these hypertensive disorders of pregnancy are multifactorial and elusive, they seem to share some common vascular-related mechanisms, including diseased spiral arteries, placental ischemia, and endothelial dysfunction. Recently, preeclampsia is being considered as a vascular disorder. Unfortunately, due to the complex etiology of preeclampsia and safety concerns on drug usage during pregnancy, there is still no effective pharmacological treatments available for preeclampsia yet. An emerging area of interest in this research field is the potential beneficial effects of dietary intervention on reducing the risk of preeclampsia. Recent studies have been focused on the association between deficiencies or excesses of some nutrients and complications during pregnancy, fetal growth and development, and later risk of cardiovascular and metabolic diseases in the offspring. In this review, we discuss the involvement of placental vascular dysfunction in preeclampsia. We summarize the current understanding of the association between abnormal placentation and preeclampsia in a vascular perspective. Finally, we evaluate several studied dietary supplementations to prevent and reduce the risk of preeclampsia, targeting placental vascular development and function, leading to improved pregnancy and postnatal outcomes.
Asunto(s)
Hipertensión Inducida en el Embarazo , Preeclampsia , Embarazo , Femenino , Humanos , Preeclampsia/metabolismo , Placenta/irrigación sanguínea , Placenta/metabolismo , Placentación , Suplementos DietéticosRESUMEN
In individuals with underlying chronic liver disease (CLD), hepatitis E virus (HEV) infection is a potential trigger of acute-on-chronic liver failure. In this systematic review, seven electronic databases were searched. Pooled incidence rates with 95% confidence intervals (95% CIs) were calculated by the Freeman-Tukey double arcsine transformation method. The association between death or liver failure and HEV superinfection in CLD patients was estimated by the odds ratios (OR) with a 95% CI. A total of 18 studies from 5 countries were eligible for systematic review. The prevalence of acute HEV infection in hospitalized CLD patients with clinical manifestations of hepatitis was 13.6%, which was significantly higher than that in CLD patients from the community (pooled prevalence 1.1%). The overall rates of liver failure and mortality in CLD patients with HEV superinfection were 35.8% (95% CI: 26.7%-45.6%) and 14.3% (95% CI: 10.6%-18.5%), respectively, with the rates in cirrhotic patients being approximately 2-fold and 4-fold higher than those in noncirrhotic patients, respectively. The risks of liver failure (OR = 5.5, 95% CI: 1.5-20.1) and mortality (OR = 5.0, 95% CI: 1.9-13.3) were significantly higher in CLD patients with HEV superinfection than in those without HEV superinfection. HEV testing in hospitalized CLD patients is necessary due to the high prevalence of HEV infection observed in hospitalized CLD patients. HEV superinfection could accelerate disease progression in patients with underlying CLD and increase mortality in these patients. HEV vaccination is appropriate for patients with pre-existing CLD.
Asunto(s)
Insuficiencia Hepática Crónica Agudizada , Virus de la Hepatitis E , Hepatitis E , Sobreinfección , Humanos , Hepatitis E/complicaciones , Hepatitis E/epidemiología , Sobreinfección/epidemiología , Sobreinfección/complicaciones , Pronóstico , Insuficiencia Hepática Crónica Agudizada/epidemiología , Insuficiencia Hepática Crónica Agudizada/complicacionesRESUMEN
BACKGROUND AND AIMS: Growing evidence suggests an important role of B cells in the development of NAFLD. However, a detailed functional analysis of B cell subsets in NAFLD pathogenesis is lacking. APPROACH AND RESULTS: In wild-type mice, 21 weeks of high fat diet (HFD) feeding resulted in NAFLD with massive macrovesicular steatosis, modest hepatic and adipose tissue inflammation, insulin resistance, and incipient fibrosis. Remarkably, Bnull (JHT) mice were partially protected whereas B cell harboring but antibody-deficient IgMi mice were completely protected from the development of hepatic steatosis, inflammation, and fibrosis. The common feature of JHT and IgMi mice is that they do not secrete antibodies, whereas HFD feeding in wild-type mice led to increased levels of serum IgG2c. Whereas JHT mice have no B cells at all, regulatory B cells were found in the liver of both wild-type and IgMi mice. HFD reduced the number of regulatory B cells and IL-10 production in the liver of wild-type mice, whereas these increased in IgMi mice. Livers of patients with advanced liver fibrosis showed abundant deposition of IgG and stromal B cells and low numbers of IL-10 expressing cells, compatible with our experimental data. CONCLUSIONS: B lymphocytes have both detrimental and protective effects in HFD-induced NAFLD. The lack of secreted pathogenic antibodies protects partially from NAFLD, whereas the presence of certain B cell subsets provides additional protection. IL-10-producing regulatory B cells may represent such a protective B cell subset.
Asunto(s)
Resistencia a la Insulina , Enfermedad del Hígado Graso no Alcohólico , Animales , Linfocitos B , Dieta Alta en Grasa/efectos adversos , Modelos Animales de Enfermedad , Fibrosis , Inmunoglobulina G , Inflamación/patología , Resistencia a la Insulina/fisiología , Interleucina-10 , Hígado/patología , Ratones , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/patologíaRESUMEN
Purpose: Reduced slow wave sleep (SWS) has been linked to hypertension in some studies. The aim of the study is to investigate the association between SWS and office blood pressure (BP) in non-hypertensive obstructive sleep apnea (OSA).Methods: This is a retrospective study of 3350 patients who underwent polysomnography (PSG) in our hospital. Based on quartiles of percent SWS, participants were classified into four groups. BP was measured manually on the randomly chosen arm in a seated position with sphygmomanometer after PSG in the morning, and the average of the second and third measurements was used for this analysis. Elevated office BP was defined as a systolic BP≥140 mmHg or diastolic BP≥90 mmHg.Results: There were 1365 patients with OSA and 597 primary snorers included in our study. In OSA group, OSA patients with SWS <13.5% had a significant elevated risk with elevated office BP (OR,1.49[95%CI 1.05-2.10], P=0.025), compared to the highest quartile (percent SWS >39.2%). However, no significant relationship between decreased SWS and elevated office BP was found in primary snorers group.Conclusion: In non-hypertensive OSA patients, decreased SWS is associated with elevated office BP.
This is the first study to investigate the association between decreased SWS and incident elevated office BP in non-hypertensive OSA patients.Our results found that in non-hypertensive OSA patients, decreased SWS is associated with elevated office BP.The relationship between decreased SWS and elevated office BP in OSA patients was evident especially in men and in those <60 years old.
Asunto(s)
Hipertensión , Apnea Obstructiva del Sueño , Sueño de Onda Lenta , Humanos , Presión Sanguínea/fisiología , Estudios Transversales , Estudios Retrospectivos , Apnea Obstructiva del Sueño/complicaciones , SueñoRESUMEN
BACKGROUND: Femoral neck fractures are serious consequence of osteoporosis (OP), numbers of people are working on the micro-mechanisms of femoral neck fractures. This study aims to investigate the role and weight of microscopic properties on femoral neck maximum load (Lmax), funding the indicator which effects Lmax most. METHODS: A total of 115 patients were recruited from January 2018 to December 2020. Femoral neck samples were collected during the total hip replacement surgery. Femoral neck Lmax, micro-structure, micro-mechanical properties, micro-chemical composition were all measured and analyzed. Multiple linear regression analyses were performed to identify significant factors that affected the femoral neck Lmax. RESULTS: The Lmax, cortical bone mineral density (cBMD), cortical bone thickness (Ct. Th), elastic modulus, hardness and collagen cross-linking ratio were all significantly decreased, whereas other parameters were significantly increased during the progression of OP (P < 0.05). In micro-mechanical properties, elastic modulus has the strongest correlation with Lmax (P < 0.05). The cBMD has the strongest association with Lmax in micro-structure (P < 0.05). In micro-chemical composition, crystal size has the strongest correlation with Lmax (P < 0.05). Multiple linear regression analysis showed that elastic modulus was most strongly related to Lmax (ß = 0.920, P = 0.000). CONCLUSIONS: Compared with other parameters, elastic modulus has the greatest influence on Lmax. Evaluation of microscopic parameters on femoral neck cortical bone can clarify the effects of microscopic properties on Lmax, providing a theoretical basis for the femoral neck OP and fragility fractures.
Asunto(s)
Fracturas del Cuello Femoral , Osteoporosis , Humanos , Cuello Femoral/diagnóstico por imagen , Densidad Ósea , Osteoporosis/diagnóstico por imagen , Fracturas del Cuello Femoral/diagnóstico por imagen , Fracturas del Cuello Femoral/cirugía , Hueso Cortical/diagnóstico por imagenRESUMEN
Though rice proteins have been applied to improve the stability of phenolic compounds, it is unclear how rice proteins affect phenolic acid's digestion and bioavailability. This study investigated the consequences of protein-ferulic acid interactions in the gastrointestinal environment. Ferulic acid and rice proteins formed complexes at room temperature, both with and without laccase. Rice protein was reported to be able to prevent ferulic acid from degrading in simulated oral fluid and remain stable in gastrointestinal fluids. With the hydrolysis of pepsin and pancreatin, rice protein-ferulic acid complexes degraded and released ferulic acid. While digested ferulic acid's DPPH scavenging activity was dramatically reduced, it was retained for the rice protein-ferulic acid complex. Moreover, the permeability coefficient of ferulic acid was not affected. Thus, rice protein is a promising food matrix to protect ferulic acid in the digestive tract and maintain the antioxidant functions of ferulic acid.