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1.
Cell Mol Life Sci ; 81(1): 62, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38280036

RESUMO

Endothelial injury and dysfunction in the artery wall fuel the process of atherosclerosis. As a key epigenetic regulator, Ash2l (Absent, small, or homeotic-Like 2) is involved in regulating vascular injury and its complications. However, the role of Ash2l in atherosclerosis has not yet been fully elucidated. Here, we found increased Ash2l expression in high-cholesterol diet-fed ApoE-/- mice and oxidized LDL (oxLDL) treated endothelial cells (ECs). Furthermore, Ash2l promoted the scavenger receptors transcription by catalyzing histone H3 lysine 4 (H3K4) trimethylation at the promoter region of transcription factor peroxisome proliferator-activated receptor-γ (PPARγ) and triggered the activation of the pro-inflammatory nuclear factor-kappa B (NF-κB) by enhancing interaction between CD36 and toll-like receptor 4 (TLR4). Meanwhile, enhanced expression of scavenger receptors drove more oxLDL uptake by ECs. In vivo studies revealed that ECs-specific Ash2l knockdown reduced atherosclerotic lesion formation and promoted fibrous cap stability in the aorta of ApoE-/- mice, which was partly associated with a reduced endothelial activation by suppressing scavenger receptors and the uptake of lipids by ECs. Collectively, our findings identify Ash2l as a novel regulator that mediates endothelial injury and atherosclerosis. Targeting Ash2l may provide valuable insights for developing novel therapeutic candidates for atherosclerosis.


Assuntos
Aterosclerose , Células Endoteliais , Camundongos , Animais , Células Endoteliais/metabolismo , Lipoproteínas LDL/farmacologia , Lipoproteínas LDL/metabolismo , Aterosclerose/metabolismo , NF-kappa B/metabolismo , Receptores Depuradores/metabolismo , Apolipoproteínas E/genética , Apolipoproteínas E/metabolismo
2.
Molecules ; 29(7)2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38611949

RESUMO

Olibanum is a resinous traditional Chinese medicine that is directly used as a powder. It is widely used in China and is often combined with other traditional Chinese medicine powders to promote blood circulation and relieve pain, as well as to treat rheumatism, rheumatoid arthritis, and osteoarthritis. Powdered traditional Chinese medicine is often easily contaminated by microorganisms and 60Co irradiation is one of the good sterilization methods. Volatile organic compounds (VOCs) are the main active ingredient of olibanum. The aim of this study was to validate the optimum doses of 60Co irradiation and its effect on VOCs. 60Co irradiation was applied in different doses of 0 kGy, 1.5 kGy, 3.0 kGy, and 6.0 kGy. Changes in VOCs were detected using gas chromatography ion mobility spectrometry. A total of 81 VOCs were identified. The odor fingerprint results showed that, with an increase in irradiation dose, most of the VOCs of olibanum changed. Through principal component analysis, cluster analysis, and partial least squares discriminant analysis, it was demonstrated that, at 1.5 kGy, the impact of radiation on the VOCs of olibanum was minimal, indicating this is a relatively good irradiation dose. This study provides a theoretical basis for the irradiation processing and quality control of resinous medicinal materials such as olibanum and it also provides a good reference for irradiation technology development and its application to functional foods, thus making it both significant from a research perspective and useful from an application perspective.


Assuntos
Radioisótopos de Cobalto , Franquincenso , Compostos Orgânicos Voláteis , Espectrometria de Mobilidade Iônica , Cromatografia Gasosa-Espectrometria de Massas , Resinas Vegetais
3.
J Med Virol ; 95(1): e28190, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36180404

RESUMO

Developing reliable, rapid, and quantitative point-of-care testing (POCT) technology of SARS-CoV-2-specific antibodies and understanding longitudinal vaccination response kinetics are highly required to restrain the ongoing coronavirus disease 2019 (COVID-19) pandemic. We demonstrate a novel portable, sensitive, and rapid chemiluminescent lab-on-fiber detection platform for detection of anti-SARS-CoV-2 antibodies: the chemiluminescent lab-on-fiber immunosensor (c-LOFI). Using SARS-CoV-2 Spike S1 RBD protein functionalized fiber bio-probe, the c-LOFI can detect anti-SARS-CoV-2 immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies with high sensitivity based on their respective horseradish peroxidase-labeled secondary antibodies. The limits of detection of anti-SARS-CoV-2 IgG and IgM antibodies were 0.6 and 0.3 ng/ml, respectively. The c-LOFI was successfully applied for direct detection of anti-SARS-CoV-2 antibodies in whole blood samples with simple dilution, which can serve as a finger prick test to rapidly detect antibodies. Furthermore, the longitudinal immune response (>12 months) kinetics following three-dose inactivated virus vaccines was evaluated based on anti-SARS-CoV-2 IgG detection results, which can provide important significance for understanding the immune mechanism against COVID-19 and identify individuals who may benefit from the vaccination and booster vaccination. The c-LOFI has great potential to become a sensitive, low-cost, rapid, high-frequency POCT tool for the detection of both SARS-CoV-2-specific antibodies and other biomarkers.


Assuntos
Técnicas Biossensoriais , COVID-19 , Humanos , COVID-19/diagnóstico , COVID-19/prevenção & controle , Imunoensaio , SARS-CoV-2 , Anticorpos Antivirais , Testes Imediatos , Vacinação , Imunoglobulina M , Imunidade , Imunoglobulina G , Glicoproteína da Espícula de Coronavírus
4.
Opt Lett ; 48(21): 5743-5746, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37910748

RESUMO

Phase modulation plays a crucial role in shaping optical fields and physical optics. However, traditional phase modulation techniques are highly dependent on angles and wavelengths, limiting their applicability in smart optical systems. Here, we propose a first-principle theory for achieving constant phase modulation independent of incident angle and wavelength. By utilizing a hyperbolic metamaterial and engineering-specific optical parameters, different reflective phase jumps are achieved and tailored for both transverse electric (TE) and transverse magnetic (TM) waves. The aimed reflection phase difference between TE and TM waves can be thus achieved omnidirectionally and achromatically. As an example, we propose a perfect omnidirectional broadband reflection quarter wave plate. This work provides fundamental insights into manipulating optical phases through optical parameter engineering.

5.
Ecotoxicol Environ Saf ; 265: 115519, 2023 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-37769580

RESUMO

Heavy metal (HM) stress is a non-negligible abiotic stress that seriously restricts crop yield and quality, while the sprout stage is the most sensitive to stress and directly impacts the growth and development of the later stage. Melatonin (N-acetyl-5-methoxytryptamine), as an exogenous additive, enhances stress resistance due to its ability to oxidize and reduce. However, few reports on exogenous melatonin to tiger nuts under HM stress have explored whether exogenous melatonin enhances plants' resistance to heavy metals. Here, "Jisha 2″ was used as material, with a stress concentration of 5 mg/L and 100 µmol/L of CdCl2 to explore whether exogenous melatonin enhances plant resistance and molecular mechanism. The result revealed that stress limits growth, while melatonin alleviated the sprout damage under stress from the phenotypes. Moreover, stress-enhanced reactive oxygen species (ROS) accumulation and membrane lipid peroxidation, while melatonin-increased ROS reduce damage via the analysis of superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and ascorbate peroxidase (APX) and malondialdehyde (MDA) content, hydrogen peroxide (H2O2), superoxide anion (O2-), and Electrolyte leakage (El). Further results indicated that HM leads to DNA damage while exogenous melatonin will repair the damage by analyzing random amplified polymorphic DNA (RAPD), DNA cross-linking, 8-hydroxy-20-deoxyguanine level, and relative density of apurinic sites. Furthermore, gene expression in the DNA-repaired pathway exhibited similar results. These results applied that exogenous melatonin released the hurt caused by HM stress, with DNA repair and ROS balance serving as candidate pathways. This study elucidated the mechanism of melatonin's influence and provided theoretical insights into its application in tiger nuts.


Assuntos
Cyperus , Melatonina , Melatonina/farmacologia , Antioxidantes/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Cádmio/metabolismo , Peróxido de Hidrogênio/metabolismo , Técnica de Amplificação ao Acaso de DNA Polimórfico , DNA/metabolismo , Estresse Oxidativo
6.
Environ Res ; 211: 113036, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35283079

RESUMO

As critical precursors of tropospheric ozone (O3) and secondary organic aerosol (SOA), volatile organic compounds (VOCs) largely influence air quality in urban environments. In this study, measurements of 102 VOCs at all five major cities in the Guanzhong Plain (GZP) were conducted during Sep.09-Oct. 13, 2017 (autumn) and Nov. 14, 2017-Jan. 19, 2018 (winter) to investigate the characteristics of VOCs and their roles in O3 and SOA formation. The average concentrations of total VOCs (TVOCs) at Xi'an (XA), Weinan (WN), Xianyang (XY), Tongchuan (TC), and Baoji (BJ) sites were in the range of 55.2-110.2 ppbv in autumn and 42.4-74.3 ppbv in winter. TVOCs concentrations were reduced by 22.4%-43.5% from autumn to winter at XA, WN and BJ. Comparatively low concentrations of TVOCs were observed in XY and TC, ranging from 53.5 to 62.7 ppbv across the sampling period. Alkanes were the major components at all sites, accounting for 26.4%-48.9% of the TVOCs during the sampling campaign, followed by aromatics (4.2%-26.4%). The average concentration of acetylene increased by a factor of up to 4.8 from autumn to winter, indicating the fuel combustion in winter heating period significantly impacted on VOCs composition in the GZP. The OH radical loss rate and maximum incremental reactivity method were employed to determine photochemical reactivities and ozone formation potentials (OFPs) of VOCs, respectively. The VOCs in XA and WN exhibited the highest reactivities in O3 formation, with the OFP of 168-273 ppbv and the OH loss rates of 19.3-40.8 s-1. Alkenes and aromatics primarily related to on-road and industrial emissions contributed 57.8%-76.3% to the total OFP. The contribution of aromatics to the SOA formation at all sites reached 94.1%-98.6%. Considering the potential source-area of VOCs, regional transport of VOCs occurred within the GZP cities.


Assuntos
Poluentes Atmosféricos , Ozônio , Compostos Orgânicos Voláteis , Aerossóis/análise , Poluentes Atmosféricos/análise , China , Monitoramento Ambiental , Ozônio/análise , Compostos Orgânicos Voláteis/análise
7.
Mikrochim Acta ; 189(6): 234, 2022 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-35624192

RESUMO

A dual-fluorescence lab-on-fiber biosensor was developed for the rapid and simultaneous on-site determination of acetamiprid and fipronil, based on time-resolved effect and indirect competitive immunoassay principle. The optical fiber modified with two hapten-protein conjugates serves as a bifunctional bio-probe. The dual-color fluorescent reporters were prepared via labeling acetamiprid and fipronil antibodies with Cy5.5 and Alexa Fluor 555, which were excited at 635-nm and 520-nm laser wavelengths, respectively. In the presence of targets, the binding sites of corresponding antibodies were occupied and less antibodies were connected to the probe surface, resulting in the reduction of fluorescence signal. The concentration of acetamiprid and fipronil was determined by measuring the fluorescence signals at 568 nm and 702 nm (emission wavelengths), respectively. Under optimal conditions, the linear response range was 14.2-225.4 ng/L for acetamiprid and 25.1-162.8 ng/L for fipronil, and the limit of detection was 6.51 ng/L and 17.8 ng/L for acetamiprid and fipronil, respectively. The method was successfully applied to the simultaneous detection of acetamiprid and fipronil in three environmental samples, and the recoveries were between 90 and 128%. The dual-fluorescence lab-on-fiber biosensor provides a feasible platform for simultaneous and rapid detection of multiple pesticide residues. A dual-fluorescence lab-on-fiber biosensor was developed for the rapid and simultaneous on-site determination of acetamiprid and fipronil. A bifunctional bio-probe was prepared from the optical fiber modified with two hapten-protein conjugates. Acetamiprid and fipronil antibodies were labeled with different fluorophores and used as dual-color fluorescent reporters.


Assuntos
Técnicas Biossensoriais , Tecnologia de Fibra Óptica , Anticorpos , Técnicas Biossensoriais/métodos , Tecnologia de Fibra Óptica/métodos , Haptenos , Neonicotinoides , Pirazóis
8.
Mikrochim Acta ; 188(8): 261, 2021 07 19.
Artigo em Inglês | MEDLINE | ID: mdl-34278534

RESUMO

The ongoing global pandemic of SARS-CoV-2 has promoted to develop novel serological testing technologies since they can be effectively complementary to RT-PCR. Here, a new all-fiber Fresnel reflection microfluidic biosensor (FRMB) was constructed through combining all-fiber optical system, microfluidic chip, and multimode fiber bio-probe. The transmission of the incident light and the collection and transmission of Fresnel reflection light are achieved using a single-multi-mode fiber optic coupler (SMFC) without any other optical separation elements. This compact design greatly simplifies the whole system structure and improves light transmission efficiency, which makes it suitable for the label-free, sensitive, and easy-to-use point-of-care testing (POCT) of targets in nanoliter samples. Based on Fresnel reflection mechanism and immunoassay principle, both the SARS-CoV-2 IgM and IgG antibodies against the SARS-CoV-2 spike protein could be sensitively quantified in 7 min using the secondary antibodies-modified multimode fiber bio-probe. The FRMB performs in one-step, is accurate, label-free, and sensitive in situ/on-site detection of SARS-CoV-2 IgM or IgG in serum with simple dilution only. The limits of detection of SARS-CoV-2 IgM and SARS-CoV-2 IgG were 0.82 ng/mL and 0.45 ng/mL, respectively. Based on our proposed theory, the affinity constants of SARS-CoV-2 IgM or IgG antibody and their respective secondary antibodies were also determined. The FRMB can be readily extended as a universal platform for the label-free, rapid, and sensitive in situ/on-site measurement of other biomarkers and the investigation of biomolecular interaction.


Assuntos
Anticorpos Antivirais/sangue , Técnicas Biossensoriais/métodos , Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , Técnicas Analíticas Microfluídicas/métodos , SARS-CoV-2/imunologia , Anticorpos Antivirais/imunologia , Humanos , Imunoensaio/métodos , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Imunoglobulina M/sangue , Imunoglobulina M/imunologia , Limite de Detecção , SARS-CoV-2/química , Sensibilidade e Especificidade , Glicoproteína da Espícula de Coronavírus/imunologia
9.
Mikrochim Acta ; 187(8): 439, 2020 07 11.
Artigo em Inglês | MEDLINE | ID: mdl-32653962

RESUMO

A reusable optofluidic point-of-care testing platform (OPOCT) was successfully constructed through integrating evanescent wave fluorescence technology into an all-fiber-based optofluidic system. The compact design of the OPOCT allows it to be portable and suitable for on-site sensitive determination of biomarkers in serum without complicated and costly procedures. The sensitivity of 90.9 pM for antibody determination is observed thanks to the high transmission efficiency of excitation light and fluorescence in the OPOCT. The affinity constant between cholylglycine (CG) and anti-CG antibody was quantified using this platform based on the proposed theory. Using the lyophilized fluorescence-labeled specific antibody and reusable fiber optic biosensor, the OPOCT is applied to the one-step sensitive determination of CG in serum, which eliminates the dearth associated with liquid reagent handling, disposable biosensors, and user intervention. A limit of detection of 0.025 µg/mL for CG is obtained, which is far more than adequate for meeting diagnostic requirements. The matrix effect of serum samples on the evanescent wave-based optofluidic biosensor can be effectively reduced by simple dilution of serum samples. The performance of the OPOCT also compared favorably with that of a commercial turbidimetric inhibition immunoassay through analyzing multiple serum samples. This platform is ready to expand to measure any other biomarker by using its specific antibody. The simplicity, sensitivity, cost-effectiveness, and robustness of the OPOCT enable the early diagnosis of disease and making a timely clinical decision. Graphical abstract .


Assuntos
Fluorometria/métodos , Ácido Glicocólico/sangue , Técnicas Analíticas Microfluídicas/métodos , Animais , Anticorpos Monoclonais/imunologia , Técnicas Biossensoriais/instrumentação , Técnicas Biossensoriais/métodos , Carbocianinas/química , Fluorescência , Corantes Fluorescentes/química , Fluorometria/instrumentação , Liofilização , Ácido Glicocólico/imunologia , Humanos , Imunoensaio/instrumentação , Imunoensaio/métodos , Dispositivos Lab-On-A-Chip , Limite de Detecção , Masculino , Camundongos Endogâmicos BALB C , Técnicas Analíticas Microfluídicas/instrumentação , Fibras Ópticas , Testes Imediatos
10.
Mikrochim Acta ; 186(11): 726, 2019 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-31655909

RESUMO

A reusable fiber optic chemiluminescent aptasensor (FOCA) is reported for the rapid and sensitive on-site detection of 17ß-estradiol (E2), an endocrine-disrupting compound frequently found in water samples. The E2-ovalbumin conjugate (E2-OVA) was covalently immobilized onto the optical fiber as a biorecognition element as well as a transducer. The affinity constant of the E2/aptamer complex was determined to be 1.35 × 106 M-1 using the FOCA. An indirect competitive assay was then developed for E2 detection. A certain concentration of HRP-E2 aptamers pre-reacted with samples containing E2 in various concentrations. Part of HRP-E2 aptamers specially bound to the sensor surface after introduction of the mixture. This catalyzed the chemiluminescece reaction of a chemiluminescent system composed of luminol and H2O2. A higher concentration of E2 led to less HRP-E2 aptamer bound to the biosensor surface, thus resulting in less chemiluminescence. Highly sensitive detection of E2 was achieved under optimal conditions, and the limit of detection is 48 ng ·L-1 (0.18 nM). The whole analytical process, including measurement and regeneration, can be performed in <15 min. The robustness of the biosensor allows its application to multiple assays with little activity loss. The selectivity, recovery, and accuracy of the sensor was demonstrated by evaluating its response to potentially interfering endocrine disruptors in spiked water samples. Graphical abstract Schematic diagram of the fiber optic chemiluminescent aptasensor system (A), detection mechanism of 17ß-estradiol (B), and its application for detection of 17ß-estradiol with rapidity and sensitivity (C and D).


Assuntos
Aptâmeros de Nucleotídeos/química , Técnicas Biossensoriais/métodos , Disruptores Endócrinos/análise , Estradiol/análise , Poluentes Químicos da Água/análise , Sequência de Bases , Técnicas Biossensoriais/instrumentação , Água Potável/análise , Tecnologia de Fibra Óptica/instrumentação , Peróxido de Hidrogênio/química , Proteínas Imobilizadas/química , Limite de Detecção , Luminol/química , Ovalbumina/química , Águas Residuárias/análise
11.
Opt Express ; 23(10): 13370-5, 2015 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-26074586

RESUMO

An imaging design approach for optical systems consisting of two aspheres which is free of astigmatism is presented in this paper. A set of implicit differential equations is derived from generalized ray tracing. The solution of the derived equations provides the profiles of the two aspheres as well as the object to image mapping. The obtained design can be used as a good starting point for optimization. Particular examples are given.

12.
Opt Express ; 22(25): 30538-46, 2014 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-25607000

RESUMO

An imaging design approach which is free of third-order astigmatism for one freeform optical surface and the image is presented in this paper. A set of differential equations is derived from generalized ray tracing. The solution of the above derived equations provides the anastigmatic freeform optical surface, the image surface and the object to image mapping. The obtained design can be used as a good starting point for optimization. As an example, a reflective freeform surface is designed for a single reflective Head Mounted Display (HMD). This example has a 3 mm pupil, 15mm eye clearance, 24-degree diagonal full field of view, and the final design yields an average MTF of 62.6% across 17 field points.

13.
Alzheimers Res Ther ; 16(1): 12, 2024 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-38238858

RESUMO

BACKGROUND: Cerebrospinal fluid (CSF) complement activation is a key part of neuroinflammation that occurs in the early stages of Alzheimer's disease (AD). However, the associations of CSF complement proteins with AD pathology, cognition, and structural neuroimaging biomarkers for AD have been rarely investigated. METHODS: A total of 210 participants (125 mild cognitive impairment [MCI] patients and 85 normal controls) were included from Alzheimer's Disease Neuroimaging Initiative (ADNI) database who measured AD pathology, cognition, and neuroimaging at baseline and every 12 months. The mixed-effect linear models were utilized to investigate longitudinal associations of CSF complement proteins with AD pathology, cognition, and neuroimaging in cognitively normal (CN) and mild cognitive impairment (MCI) subjects. Causal mediation analyses were conducted to explore the potential mediators between CSF complement proteins and cognitive changes. RESULTS: We found that the subjects with low CSF complement protein levels at baseline had worse outcomes in AD pathology, indicated by their lowest concentrations observed in A + and A + T + individuals. The reduced CSF complement proteins were associated with faster accumulation of tau among CN subjects and with cognitive decline and greater brain atrophy of specific regions among MCI subjects. Furthermore, mediation analyses showed that the effects of CSF complement proteins on cognitive performance were partially mediated by regional brain structures (mediation proportions range from 19.78 to 94.92%; p < 0.05). CONCLUSIONS: This study demonstrated that CSF complement proteins were involved in the early progression of AD. Our results indicated that regional brain atrophy might be a plausible way to connect CSF complement protein levels and cognition.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Humanos , Idoso , Doença de Alzheimer/líquido cefalorraquidiano , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Cognição , Disfunção Cognitiva/líquido cefalorraquidiano , Biomarcadores/líquido cefalorraquidiano , Atrofia/patologia , Proteínas do Sistema Complemento , Proteínas tau/líquido cefalorraquidiano , Peptídeos beta-Amiloides/líquido cefalorraquidiano
14.
J Affect Disord ; 352: 87-100, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38360368

RESUMO

BACKGROUND: Suicide has been recognized as a major global public health issue. Depressed adolescents are more prone to experiencing it. We explore risk factors and their differences on suicidal ideation and suicide attempts to further enhance our understanding of suicidal behavior. METHODS: 2343 depressed adolescents aged 12-18 from 9 provinces/cities in China participated in this cross-sectional study. We utilized decision tree model, incorporating 32 factors encompassing participants' suicidal behavior. The feature importance of each factor was measured using Gini coefficients. RESULTS: The decision tree model demonstrated a good fit with high accuracy (SI = 0.86, SA = 0.85 and F-Score (SI = 0.85, SA = 0.83). The predictive importance of each factor varied between groups with suicidal ideation and with suicide attempts. The most significant risk factor in both groups was depression (SI = 16.7 %, SA = 19.8 %). However, factors such as academic stress (SI = 7.2 %, SA = 1.6 %), hopelessness (SI = 9.1 %, SA = 5.0 %), and age (SI = 7.1 %, SA = 3.2 %) were more closely associated with suicidal ideation than suicide attempts. Factors related to the schooling status (SI = 3.5 %, SA = 10.1 %), total years of education (SI = 2.6 %, SA = 8.6 %), and loneliness (SI = 2.3 %, SA = 7.4 %) were relatively more important in the suicide attempt stage compared to suicidal ideation. LIMITATIONS: The cross-sectional design limited the ability to capture changes in suicidal behavior among depressed adolescents over time. Possible bias may exist in the measurement of suicidal ideation. CONCLUSION: The relative importance of each risk factor for suicidal ideation and attempted suicide varies. These findings provide further empirical evidence for understanding suicide behavior. Targeted treatment measures should be taken for different stages of suicide in clinical interventions.


Assuntos
Ideação Suicida , Tentativa de Suicídio , Humanos , Adolescente , Estudos Transversais , Fatores de Risco , Árvores de Decisões
15.
Neurobiol Aging ; 137: 55-61, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38422799

RESUMO

This study explored the associations between peripheral immunity with cerebral small vessel diseases. Older adults without dementia from the Alzheimer's Disease Neuroimaging Initiative were investigated. Peripheral blood was obtained, and magnetic resonance imaging was performed to measure cerebral microbleeds (CMB), lacunar infarctions (LI), and white matter hyperintensities (WMH). Multivariable-adjusted regression models, linear mixed-effects models, and the Spearman correlations were used to evaluate the associations. At baseline, individuals with greater neutrophils (odds ratio [OR] =1.10, 95% confidence interval [CI] 1.00-1.20, p=0.042) and monocytes (OR=1.12, 95% CI 1.02-1.22, p=0.016) had higher WMH volume. On the contrary, a higher lymphocyte-to-monocyte ratio (LMR) was related to lower WMH volume (OR=0.91, 95% CI 0.82-1.00, p=0.041). Longitudinally, higher neutrophils (ρ=0.084, p=0.049) and NLR (ρ=0.111, p=0.009) predicted accelerated progression of WMH volume, while a greater LMR (ρ=-0.101, p=0.018) was linked to slower growth of WMH volume. Nevertheless, associations between peripheral immunity with CMB or LI were not observed at baseline and follow-up. Our study found that peripheral immune indexes could serve as convenient noninvasive biomarkers of WMH.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Demência , Substância Branca , Humanos , Idoso , Estudos Longitudinais , Doenças de Pequenos Vasos Cerebrais/patologia , Imageamento por Ressonância Magnética , Neuroimagem , Demência/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia
16.
J Ethnopharmacol ; 333: 118467, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-38909826

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Phytolacca acinosa Roxb. (PAR) is a Traditional Chinese Medicinal (TCM) plant with a broad global distribution encompassing 35 species, four of which are found in the People's Republic of China. It occupies a significant role in both Oriental and American traditional medicine, employed in treating a range of conditions such as edema, inflammation, dermatitis, and rheumatism. PAR is also used as a molluscicide and for addressing tumors and bronchitis. The plant is documented in the Chinese Pharmacopoeia and has a longstanding history in TCM, particularly for its diuretic properties and in treating ailments such as edema, swelling, and ulcers. Notably, PAR has demonstrated potent inhibitory effects against the A549 human lung cancer cell line, underscoring its potential in contributing to the development of novel cancer therapeutics. AIM OF THE STUDY: The research aims to elucidate the active components of PAR and their mechanisms in treating hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Employing network pharmacology, this study predicted the principal active compounds and key targets of PAR. A holistic methodology incorporating biological network analysis, transcriptomics sequencing, molecular docking, and molecular dynamics (MD) simulations was utilized to forecast the effects of PAR on HCC, with empirical evidence supporting these findings. RESULTS: Network pharmacology identified xanthomicrol as the foremost active compound in PAR. The tumor-suppressive functions of PAR, as indicated by KEGG pathway analysis and transcriptomics sequencing, predominantly occur via the PI3K/AKT pathway. Molecular docking and dynamics simulations demonstrated the high affinity of xanthomicrol towards TNF, MMP9, PPARG, KDR, and MMP2. In vivo experiments verified the efficacy of xanthomicrol in curtailing HCC tumor growth, while in vitro assessments revealed its substantial impact on the proliferation and apoptosis of HepG2 and HCCLM3 cells. Moreover, the study indicates that xanthomicrol may modulate the expression of TNF, MMP9, PPARG, KDR, and MMP2 in HCC cells and inhibit the activation of the PI3K/AKT pathway. CONCLUSIONS: Xanthomicrol, a principal active component of PAR, has been identified to impede the growth of HCC by targeting the PI3K/Akt/MMP9 pathway. This insight could enhance therapeutic approaches for HCC.


Assuntos
Antineoplásicos Fitogênicos , Carcinoma Hepatocelular , Neoplasias Hepáticas , Farmacologia em Rede , Phytolacca , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Neoplasias Hepáticas/tratamento farmacológico , Phytolacca/química , Animais , Transcriptoma/efeitos dos fármacos , Células Hep G2 , Camundongos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
17.
J Alzheimers Dis ; 98(2): 629-642, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38427482

RESUMO

Background: Frailty is a vulnerability state increasing the risk of many adverse health outcomes, but little is known about the effects of frailty on neuropsychiatric health. Objective: To explore the associations between frailty and the risk of neuropsychiatric symptoms (NPSs) in Alzheimer's disease (AD), especially in its different clinical stages. Methods: We included 2,155 individuals assessed using modified frailty index-11 (mFI-11), Neuropsychiatric Inventory (NPI) and Neuropsychiatric Inventory Questionnaire (NPI-Q) in the Alzheimer's Disease Neuroimaging Initiative (ADNI). The relationships between frailty and NPSs were explored with logistic regression models and Cox proportional hazard regression models. Causal mediation analyses were conducted to explore the mediation factors between frailty and NPSs. Results: Among mild cognitive impairment (MCI) participants, frailty was cross-sectionally associated with an increased risk of apathy, and longitudinally associated with increased risk of depression and apathy. Among AD participants, frailty was cross-sectionally associated with increased risk of depression and anxiety, and longitudinally associated with an increased risk of apathy. Among participants with cognitive progression, frailty was associated with increased risk of depression and apathy. In MCI participants, the influence of frailty on NPSs was partially mediated by hippocampus volume, whole brain volume, and monocytes, with mediating proportions ranging from 8.40% to 9.29%. Conclusions: Frailty was associated with NPSs such as depression, anxiety, and apathy among MCI, AD, and cognitive progression participants. Atrophy of the hippocampus and whole brain, as well as peripheral immunity may be involved in the potential mechanisms underlying the above associations.


Assuntos
Doença de Alzheimer , Apatia , Disfunção Cognitiva , Fragilidade , Humanos , Doença de Alzheimer/complicações , Doença de Alzheimer/diagnóstico por imagem , Estudos Longitudinais , Fragilidade/complicações , Disfunção Cognitiva/psicologia , Testes Neuropsicológicos
18.
J Integr Plant Biol ; 55(3): 250-61, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23190411

RESUMO

The plant actin depolymerizing factor (ADF) binds to both monomeric and filamentous actin, and is directly involved in the depolymerization of actin filaments. To better understand the actin binding sites of the Arabidopsis thaliana L. AtADF1, we generated mutants of AtADF1 and investigated their functions in vitro and in vivo. Analysis of mutants harboring amino acid substitutions revealed that charged residues (Arg98 and Lys100) located at the α-helix 3 and forming an actin binding site together with the N-terminus are essential for both G- and F-actin binding. The basic residues on the ß-strand 5 (K82/A) and the α-helix 4 (R135/A, R137/A) form another actin binding site that is important for F-actin binding. Using transient expression of CFP-tagged AtADF1 mutant proteins in onion (Allium cepa) peel epidermal cells and transgenic Arabidopsis thaliana L. plants overexpressing these mutants, we analyzed how these mutant proteins regulate actin organization and affect seedling growth. Our results show that the ADF mutants with a lower affinity for actin filament binding can still be functional, unless the affinity for actin monomers is also affected. The G-actin binding activity of the ADF plays an essential role in actin binding, depolymerization of actin polymers, and therefore in the control of actin organization.


Assuntos
Fatores de Despolimerização de Actina/química , Fatores de Despolimerização de Actina/metabolismo , Actinas/metabolismo , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/metabolismo , Fatores de Despolimerização de Actina/genética , Proteínas de Arabidopsis/genética , Sítios de Ligação/genética , Mutação
19.
Artigo em Inglês | MEDLINE | ID: mdl-36767540

RESUMO

The Fenwei Plain (FWP) remains one of the worst PM2.5-polluted regions in China, although its air quality has improved in recent years. To evaluate the regional transport characteristics of PM2.5 emitted by coal-fired power plants in the FWP in wintertime, the primary PM2.5, SO2, and NOx emissions from coal-fired power plants with large units (≥300 MW) in 11 cities of the area in January 2019 were collected based on the Continuous Emission Monitoring System (CEMS). The spatial distribution and source contribution of primary and secondary PM2.5 concentrations were investigated using the Weather Research and Forecast (WRF) model and the California Puff (CALPUFF) model. The results showed that secondary PM2.5 was transported over a larger range than primary PM2.5 and that secondary nitrate was the main component of the total PM2.5 concentration, accounting for more than 70%. High concentrations of primary, secondary, and total PM2.5 mainly occurred in the Shaanxi region of the FWP, especially in Xianyang, where the PM2.5 concentrations were the highest among the 11 cities, even though its pollutant emissions were at moderate levels. The PM2.5 concentrations in Sanmenxia and Yuncheng primarily came from regional transport, accounting for 64% and 68%, respectively, while those in other cities were dominated by local emissions, accounting for more than 63%. The results may help to understand the regional transport characteristics of pollutants emitted from elevated point sources over a complex terrain.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Poluentes Ambientais , Poluentes Atmosféricos/análise , Material Particulado/análise , Carvão Mineral , Monitoramento Ambiental/métodos , China , Cidades , Centrais Elétricas
20.
Environ Sci Pollut Res Int ; 30(36): 85125-85138, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37380852

RESUMO

Understanding the sources and characteristics of PM2.5-bound PAHs from traffic-related pollution can provide valuable data for mitigating air contamination from traffic in local urban regions. However, little information on PAHs is available regarding the typical arterial highway-Qinling Mountains No.1 tunnel in Xi'an. We estimated the profiles, sources, and emission factors of PM2.5-bound PAHs in this tunnel. The total PAH concentrations were 22.78 ng·m-3 and 52.80 ng·m-3 at the tunnel middle and exit, which were 1.09 and 3.84 times higher than that at the tunnel entrance. Pyr, Flt, Phe, Chr, BaP, and BbF were the dominant PAH species (representing approximately 78.01% of total PAHs). The four rings PAHs were dominant (58%) among the total PAH concentrations in PM2.5. The results demonstrated that diesel and gasoline vehicles exhaust emissions contributed 56.81% and 22.60% to the PAHs, respectively, while the corresponding value for together brakes, tyre wear, and road dust was 20.59%. The emission factors of total PAHs were 29.35 µg·veh-1·km-1, and emission factors of 4 rings PAHs were significantly higher than those of the other PAHs. The sum of ILCR was estimated to be 1.41×10-4, which accorded with acceptable level of cancer risk (10-6-10-4), PAHs should not ignored as they still affect the public health of inhabitants. This study shed light on PAH profiles and traffic-related sources in the tunnel, thereby facilitating the assessment of control measures targeting PAHs in local areas.


Assuntos
Poluentes Atmosféricos , Hidrocarbonetos Policíclicos Aromáticos , Hidrocarbonetos Policíclicos Aromáticos/análise , Poluentes Atmosféricos/análise , Monitoramento Ambiental , Medição de Risco , Emissões de Veículos/análise , China , Poeira/análise , Material Particulado/análise
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