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1.
Prostaglandins Other Lipid Mediat ; 175: 106906, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39265779

RESUMEN

Hyperlipidemia, obesity and gut dysbiosis are pivotal risk factors for atherosclerotic cardiovascular disease (ACVD). Supplementation of Akkermansia muciniphila (AKK) has also been proven to be effective in the prevention and treatment of obesity and other metabolic disorders. Here we found that AKK was more abundant in healthy control than ACVD patients via metagenomic sequencing on fecal samples. Subsequently, we investigated the role and underlying mechanism of AKK on obesity-associated atherosclerosis. AKK intervention partially reversed the exacerbation of atherosclerotic lesion formation in ApoE-/- mice by improving dyslipidemia. Interestingly, replenishment with AKK significantly enhanced cardiac function and reduced the body weight. It also reduced pro-inflammatory cytokine IL-6 and increased anti-inflammatory IL-10 in the circulation. Additionally, AKK colonization dramatically regulated gut microbiota and increased the abundance of Lactobacillaceae. Our findings have provided novel insights into the therapeutic potential of AKK as a beneficial microbe for treating atherosclerotic-associated cardiovascular diseases.

2.
Planta ; 252(2): 27, 2020 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-32712728

RESUMEN

MAIN CONCLUSION: This study demonstrates that brassinosteroid is essential for seedling and shoot growth in moso bamboo. The shoot of moso bamboo is known to grow extremely fast. The roles of phytohormones in such fast growth of bamboo shoot remain unclear. Here we reported that endogenous brassinosteroid (BR) is a major factor promoting bamboo shoot internode elongation. Reducing endogenous brassinosteroid level by its biosynthesis inhibitor propiconazole stunted shoot growth in seedling stage, whereas exogenous BR application promoted scale leaf elongation and the inclination of lamina joint of leaves and scale leaves. Genome-wide transcriptome analysis identified hundreds of genes whose expression levels are altered by BR and propiconazole in shoots and roots of bamboo seedling. The data show that BR regulates cell wall-related genes, hydrogen peroxide catabolic genes, and auxin-related genes. Our study demonstrates an essential role of BR in fast growth bamboo shoots and identifies a large number of BR-responsive genes in bamboo seedlings.


Asunto(s)
Brasinoesteroides/metabolismo , Perfilación de la Expresión Génica , Regulación de la Expresión Génica de las Plantas , Poaceae/genética , Poaceae/fisiología , Plantones/genética , Plantones/fisiología , Transcriptoma/genética , Brasinoesteroides/farmacología , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Ácidos Indolacéticos/farmacología , Fenotipo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/genética , Brotes de la Planta/efectos de los fármacos , Brotes de la Planta/genética , Brotes de la Planta/crecimiento & desarrollo , Poaceae/efectos de los fármacos , Plantones/efectos de los fármacos , Plantones/crecimiento & desarrollo , Transcriptoma/efectos de los fármacos , Triazoles/farmacología
3.
Front Nutr ; 11: 1374992, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38899319

RESUMEN

Background: There is limited research on the relationship between Systemic Oxidative Stress (SOS) status and inflammatory indices. Adding onto existing literature, this study aimed to examine the association between dietary Oxidative Balance Score (OBS) and lifestyle OBS (which make up the overall OBS), and Cardiovascular Disease (CVD) prevalence at different Systemic Immune Inflammation Index (SII) and Systemic Inflammatory Response Index (SIRI) levels. Methods: This study involved 9,451 subjects selected from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. The OBS comprised 20 dietary and lifestyle factors. Statistical methods included Weighted Linear Regression Analysis (WLRA), Logistic Regression Analysis (LRA), Sensitivity Analysis (SA), and Restricted Cubic Spline (RCS) analysis. Results: The multivariate WLRA revealed that OBS was significantly negatively correlated with both SII (ß = -5.36, p < 0.001) and SIRI (ß = -0.013, p < 0.001) levels. In SA, removing any single OBS component had no significant effect on the WLRA results of SII and SIRI. Further subgroup analyses revealed that OBS was more impactful in lowering SII in women than in men. Additionally, OBS was more significantly negatively correlated with SII and SIRI in the low-age group than in the high-age group. Moreover, RCS analysis confirmed this linear relationship. Compared to dietary OBS, lifestyle OBS exerted a more significant effect on Coronary Artery Disease (CAD) (OR: 0.794, p = 0.002), hypertension (OR: 0.738, p < 0.001), Congestive Heart Failure (CHF) (OR: 0.736, p = 0.005), Myocardial Infarction (MI) (OR: 0.785, p = 0.002), and stroke (OR: 0.807, p = 0.029) prevalence. Furthermore, SIRI exhibited a significant interaction in the relationship between overall OBS, dietary OBS, and CHF (P for interaction < 0.001). On the other hand, SII had a significant interaction in the relationship between overall OBS, dietary OBS, and MI (P for interaction < 0.05). Conclusion: OBS, including lifestyle and dietary OBS, were significantly negatively associated with SII and SIRI. Higher lifestyle OBS was associated with reduced risks of CAD, hypertension, CHF, MI, and stroke.

4.
bioRxiv ; 2024 Sep 08.
Artículo en Inglés | MEDLINE | ID: mdl-39282327

RESUMEN

Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), is the leading cause of mortality due to a single infectious organism. While generally curable, TB requires a lengthy and complex antibiotic regimen, due in large part to bacteria that can shift to a persistent state in the presence of antibiotic pressure. Rel Mtb is the primary enzyme regulating the stringent response, which contributes to the metabolic shift of Mtb to a persistent state. Targeting Rel Mtb with a vaccine to eliminate persistent bacteria through the induction of Rel Mtb -specific T-cell immunity in combination with antibiotics to kill dividing bacteria has shown promise in model systems. In a mouse model of Mtb infection, a vaccine created by genetically fusing rel Mtb to the chemokine macrophage inflammatory protein 3α ( MIP3 α), a ligand for the CC chemokine receptor type 6 (CCR6) present on immature dendritic cells, has been shown to enhance T-cell responses and accelerate eradication of infection in mouse models compared to a vaccine lacking the chemokine component. In this study, immunogenicity studies in the mouse and rhesus macaque models provide evidence that intranasal administrations of the DNA form of the MipRel vaccine led to enhanced lung infiltration of T cells after a series of immunizations. Furthermore, despite similar T-cell immunity seen in PBMCs between MipRel and Rel vaccinations, lung and bronchoalveolar lavage cell samples are more enriched for cytokine-secreting T cells in MipRel groups compared to Rel groups. We conclude that intranasal immunization with a MIP-3α fusion vaccine represents a novel strategy for use of a simple DNA vaccine formulation to elicit T-cell immune responses within the respiratory tract. That this formulation is immunogenic in a non-human primate model historically viewed as poorly responsive to DNA vaccines indicates the potential for clinical application in the treatment of Mtb infection, with possible application to other respiratory pathogens. Future studies will further characterize the protective effect of this vaccination platform.

5.
Res Sq ; 2024 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-39041038

RESUMEN

Resurgence in malaria has been noted in 2022 with 249 million clinical cases resulting in 608,000 deaths, mostly in children under five. Two vaccines, RTS, S, and more recently R21, targeting the circumsporozoite protein (CSP) are recommended by the WHO but are not yet widely available. Strong humoral responses to neutralize sporozoites before they can infect the hepatocytes are important for vaccine-mediated protection. Suboptimal protection conferred by these first-generation vaccines highlight the need for approaches to improve vaccine-induced immune responses. With the recent success of mRNA-LNP vaccines against COVID-19, there is growing interest in leveraging this approach to enhance malaria vaccines. Here, we present the development of a novel chemokine fusion mRNA vaccine aimed at boosting immune responses to PfCSP by targeting the immunogen to immature dendritic cells (iDC). Vaccination of mice with mRNA encoding full-length CSP fused to macrophage inflammatory protein 3 alpha (MIP3α) encapsulated within lipid nanoparticles (LNP) elicited robust CD4+ T cell responses and enhanced antibody titers against NANP repeat epitopes compared to a conventional CSP mRNA-LNP vaccine. Importantly, the CSP-MIP3α fusion vaccine provided significantly greater protection against liver infection upon challenge with P. berghei PfCSP transgenic sporozoites. This enhanced protection was associated with multifunctional CD4+ T cells levels and anti-NANP repeat titers. This study highlights the potential to augment immune responses to PfCSP through iDC targeting and bolster protection against malaria liver infection.

6.
Front Immunol ; 15: 1292059, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38370404

RESUMEN

Background: Previous studies have demonstrated enhanced efficacy of vaccine formulations that incorporate the chemokine macrophage inflammatory protein 3α (MIP-3α) to direct vaccine antigens to immature dendritic cells. To address the reduction in vaccine efficacy associated with a mutation in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mutants, we have examined the ability of receptor-binding domain vaccines incorporating MIP-3α to sustain higher concentrations of antibody when administered intramuscularly (IM) and to more effectively elicit lung T-cell responses when administered intranasally (IN). Methods: BALB/c mice aged 6-8 weeks were immunized intramuscularly or intranasally with DNA vaccine constructs consisting of the SARS-CoV-2 receptor-binding domain alone or fused to the chemokine MIP-3α. In a small-scale (n = 3/group) experiment, mice immunized IM with electroporation were followed up for serum antibody concentrations over a period of 1 year and for bronchoalveolar antibody levels at the termination of the study. Following IN immunization with unencapsulated plasmid DNA (n = 6/group), mice were evaluated at 11 weeks for serum antibody concentrations, quantities of T cells in the lungs, and IFN-γ- and TNF-α-expressing antigen-specific T cells in the lungs and spleen. Results: At 12 months postprimary vaccination, recipients of the IM vaccine incorporating MIP-3α had significantly, approximately threefold, higher serum antibody concentrations than recipients of the vaccine not incorporating MIP-3α. The area-under-the-curve analyses of the 12-month observation interval demonstrated significantly greater antibody concentrations over time in recipients of the MIP-3α vaccine formulation. At 12 months postprimary immunization, only recipients of the fusion vaccine had concentrations of serum-neutralizing activity deemed to be effective. After intranasal immunization, only recipients of the MIP-3α vaccine formulations developed T-cell responses in the lungs significantly above those of PBS controls. Low levels of serum antibody responses were obtained following IN immunization. Conclusion: Although requiring separate IM and IN immunizations for optimal immunization, incorporating MIP-3α in a SARS-CoV-2 vaccine construct demonstrated the potential of a stable and easily produced vaccine formulation to provide the extended antibody and T-cell responses that may be required for protection in the setting of emerging SARS-CoV-2 variants. Without electroporation, simple, uncoated plasmid DNA incorporating MIP-3α administered intranasally elicited lung T-cell responses.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , Animales , Ratones , Formación de Anticuerpos , Quimiocinas , COVID-19/prevención & control , Vacunas contra la COVID-19/inmunología , ADN , Pulmón , SARS-CoV-2 , Linfocitos T
7.
bioRxiv ; 2024 Sep 07.
Artículo en Inglés | MEDLINE | ID: mdl-39282461

RESUMEN

Mycobacterium tuberculosis ( Mtb) is one of the leading infectious causes of death worldwide. There is no available licensed therapeutic vaccine that shortens active tuberculosis (TB) disease drug treatment and prevents relapse, despite the World Health Organization's calls. Here, we show that an intranasal DNA vaccine containing a fusion of the stringent response rel Mtb gene with the gene encoding the immature dendritic cell-targeting chemokine, MIP-3α/CCL20, shortens the duration of curative TB treatment in immunocompetent mice. Compared to the first-line regimen for drug-susceptible TB alone, our novel adjunctive vaccine induced greater Rel Mtb -specific T-cell responses associated with optimal TB control in spleen, blood, lungs, mediastinal lymph nodes, and bronchoalveolar lavage (BAL) fluid. These responses were sustained, if not augmented, over time. It also triggered more effective dendritic cell recruitment, activation, and colocalization with T cells, implying enhanced crosstalk between innate and adaptive immunity. Moreover, it potentiated a 6-month TB drug-resistant regimen, rendering it effective across treatment regimens, and also showed promising results in CD4+ knockout mice, perhaps due to enhanced Rel-specific CD8+ T-cell responses. Notably, our novel fusion vaccine was also immunogenic in nonhuman primates, the gold standard animal model for TB vaccine studies, eliciting antigen-specific T-cell responses in blood and BAL fluid analogous to those observed in protected mice. Our findings have critical implications for therapeutic TB vaccine clinical development in immunocompetent and immunocompromised populations and may serve as a model for defining immunological correlates of therapeutic vaccine-induced protection. One sentence summary: A TB vaccine shortens curative drug treatment in mice by eliciting strong TB-protective immune responses and induces similar responses in macaques.

8.
Quant Imaging Med Surg ; 13(9): 5748-5758, 2023 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-37711832

RESUMEN

Background: Quantification of vertebral arteries can provide insights into basilar curvature and plaque. Therefore, this retrospective study aimed at identifying the dominant vertebral artery (VA) causing basilar artery (BA) curvature and to further quantify the effect of dominant VA angle on BA curvature and BA plaque using high-resolution magnetic resonance imaging (HRMRI) and 3-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA). Methods: This retrospective analysis included 521 participants who underwent HRMRI in the China-Japan Friendship Hospital from November 2015 to October 2021 for neurological symptoms or signs. The VA angle more related to BA curvature was defined as the dominant VA angle. Multivariable linear regression analysis was used to evaluate the relationship between the dominant VA angle and mid-BA angle, while multivariable logistics regression was used to evaluate the influence of the dominant VA angle and clinical risk factors on BA plaque. Results: In total, 259 participants were included in this study (mean age 53.71±13.12 years; 146 males). The balanced-type participants had a significantly lower probability of BA plaques (P<0.001). The Chi-squared test showed that the BA curvature direction was significantly associated with the side with larger VA diameter (P<0.001) and larger VA angle (P<0.001). As a result, the VA angle on the side with the larger diameter or the larger VA angle when the diameters were similar was considered to be the dominant VA angle. The dominant VA angle was independently correlated with the mid-BA angle (P<0.001). In addition, the dominant VA angle was also an independent risk factor for BA plaque. Additionally, 80° was the cutoff value of the dominant VA angle, and when the dominant VA angle was greater than 80°, the risk of BA plaque increased about 18-fold [odds ratio, 18.951; 95% confidence interval (CI): 4.545-79.026; P<0.001]. Conclusions: The dominant VA angle was independently associated with BA plaque, and a dominant VA angle greater than 80° may be a marker for a high risk of posterior circulation atherosclerosis.

9.
Nat Prod Res ; : 1-8, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37967021

RESUMEN

In this study, total flavonoids from the Chinese herb tulip were extracted by ultrasound-assisted extraction (UAE), their main components were analysed and confirmed, and their antioxidant and anti-inflammatory activities were evaluated. The results showed that the extraction rate of total flavonoids from the Chinese herb tulip reached 390.77 ± 3.88 mg·g-1 after optimisation by one-factor test and response surface methodology. 23 compounds were identified in the solution of total flavonoids from the Chinese herb tulip, including 18 flavonoids such as Hyperoside, Quercetin, Astilbin, etc., and the effects of total flavonoids of the Chinese herb tulip (TFT) on ABTS+ radicals, DPPH radicals, and superoxide anion with a good scavenging rate, good total reducing power, and total antioxidant capacity. Secondly, TFT showed good inhibition of 5-lipoxygenase (5-LOX) and cyclooxygenase-2 (COX-2).

10.
J Atheroscler Thromb ; 30(2): 182-191, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-35418542

RESUMEN

AIMS: The basilar artery (BA) geometry and plaque characteristics may play an important role in the development of atherosclerosis. This study was performed to explore the relationship between the mid-BA angle and plaque characteristics and its effect on pontine infarction using high-resolution magnetic resonance imaging and three-dimensional time-of-flight magnetic resonance angiography. METHODS: In total, 77 patients with BA plaques were included in this study. According to the presence of acute pontine infarction on diffusion-weighted imaging, the patients were divided into a pontine infarction group and pontine non-infarction group. The mid-BA angle, plaque burden, stenosis ratio, positive remodeling, and intraplaque hemorrhage were evaluated to investigate their effects on stroke. RESULTS: The pontine infarction group had a greater plaque burden, stenosis ratio, positive remodeling, and mid-BA angle than the pontine non-infarction group. The correlation between the plaque burden and mid-BA angle was the highest (r=0.441, P<0.001). Multivariate logistic regression analysis showed that the plaque burden (odds ratio, 1.164; 95% confidence interval, 1.093-1.241; P<0.001) was an independent risk factor for pontine infarction. CONCLUSION: The mid-BA angle may increase the incidence of pontine infarction by increasing the plaque burden.


Asunto(s)
Aterosclerosis , Infartos del Tronco Encefálico , Placa Aterosclerótica , Humanos , Arteria Basilar/diagnóstico por imagen , Arteria Basilar/patología , Constricción Patológica/complicaciones , Placa Aterosclerótica/complicaciones , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/patología , Aterosclerosis/patología , Imagen por Resonancia Magnética/métodos , Infartos del Tronco Encefálico/complicaciones , Infartos del Tronco Encefálico/diagnóstico por imagen
11.
Cells ; 11(15)2022 07 23.
Artículo en Inglés | MEDLINE | ID: mdl-35892572

RESUMEN

Fusarium head blight (FHB), or scab, caused by Fusarium species, is an extremely destructive fungal disease in wheat worldwide. In recent decades, researchers have made unremitting efforts in genetic breeding and control technology related to FHB and have made great progress, especially in the exploration of germplasm resources resistant to FHB; identification and pathogenesis of pathogenic strains; discovery and identification of disease-resistant genes; biochemical control, and so on. However, FHB burst have not been effectively controlled and thereby pose increasingly severe threats to wheat productivity. This review focuses on recent advances in pathogenesis, resistance quantitative trait loci (QTLs)/genes, resistance mechanism, and signaling pathways. We identify two primary pathogenetic patterns of Fusarium species and three significant signaling pathways mediated by UGT, WRKY, and SnRK1, respectively; many publicly approved superstar QTLs and genes are fully summarized to illustrate the pathogenetic patterns of Fusarium species, signaling behavior of the major genes, and their sophisticated and dexterous crosstalk. Besides the research status of FHB resistance, breeding bottlenecks in resistant germplasm resources are also analyzed deeply. Finally, this review proposes that the maintenance of intracellular ROS (reactive oxygen species) homeostasis, regulated by several TaCERK-mediated theoretical patterns, may play an important role in plant response to FHB and puts forward some suggestions on resistant QTL/gene mining and molecular breeding in order to provide a valuable reference to contain FHB outbreaks in agricultural production and promote the sustainable development of green agriculture.


Asunto(s)
Fusarium , Agricultura , Fusarium/genética , Enfermedades de las Plantas/genética , Enfermedades de las Plantas/microbiología , Sitios de Carácter Cuantitativo/genética , Triticum/genética , Triticum/microbiología
12.
Front Neurosci ; 15: 823876, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-35250438

RESUMEN

OBJECTIVES: This study analyzed differences in the mean cerebral blood flow (mCBF) and arterial transit time (ATT) of the anterior and posterior circulations between patients with intracranial atherosclerotic stenosis (ICAS) and control subjects. We also investigated the correlation between ATT and mCBF in the two groups, and evaluated whether the blood flow velocity of the extracranial carotid/vertebral arteries can influence mCBF. METHODS: A total of 32 patients with ICAS were prospectively enrolled at the Radiology Department of the China-Japan Friendship Hospital between November 2020 and September 2021. All patients had extensive arterial stenosis, with 17 having cerebral arterial stenosis in the anterior circulation and 15 in the posterior circulation. Thirty-two healthy subjects were enrolled as a control group. Enhanced arterial spin labeling (eASL) imaging was performed using a 3.0-T GE magnetic resonance imaging scanner, and all patients underwent carotid and vertebral Doppler ultrasound examinations. CereFlow software was used for post-processing of the eASL data, to obtain cerebral perfusion parameters such as mCBF and ATT. Independent samples t-tests were used to analyze and compare mCBF and ATT of the anterior circulation (frontal lobe, parietal lobe, and insula) and posterior circulation (occipital lobe, cerebellum) between the patient and control groups. The relationships of ATT and mCBF in the two groups were evaluated with Pearson's correlation. The blood flow velocity of the extracranial internal carotid/vertebral arteries, including the peak systolic velocity (PSV), end diastolic velocity (EDV), mean PSV (mPSV), and mean EDV (mEDV), was compared between the control and study groups using t-tests. Multiple linear regression analysis was then applied to determine the factors associated with mCBF in the two groups. RESULTS: The mCBFs of the anterior and posterior circulations in the patient group were lower than those of the control group. The ATTs in the patient group were all significantly longer than those of the control group (p < 0.05). Except for the insula in the control group, significant correlations were found between ATT and mCBF in all other investigated locations in the two groups (p < 0.05). The blood flow velocity of the extracranial internal carotid/vertebral arteries differed significantly between the control and patient groups (p < 0.05). The multiple linear regression analysis revealed that in patients with ICAS, mPSV of the vertebral arteries and local ATT correlated with mCBF of the occipital lobes and the cerebellum, respectively (p < 0.05). In contrast, there was no significant correlation within the anterior circulation (frontal lobes, parietal lobes, and insula). CONCLUSION: There was a significant relationship between ATT and mCBF in patients with ICAS. Extracranial blood flow may influence intracranial hemodynamics in the posterior circulation in patients with ICAS. The maintenance of extracranial blood flow is of great significance in the preservation of intracranial hemodynamics.

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