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1.
Regen Ther ; 18: 391-400, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34722835

RESUMO

Introduction: Osteoporosis, a common skeletal disorder mainly affecting postmenopausal women, is characterized by the imbalance between osteogenesis and osteoclastogenesis. Circ_0134944 has been recently found to be upregulated in postmenopausal osteoporosis (PMOP) patients. However, its role in osteogenesis remains unknown. Here we aimed to explore the role of circ_0134944 in osteogenesis and reveal the underlying mechanism. Methods: qRT-PCR was used to determine the expression of circ_0134944, miR-127-5p, PDX1 and SPHK1 in the blood mononuclear cells (BMCs) of PMOP patients. Bone marrow mesenchymal stem cells (BMSCs) were used as the cellular model. Western blotting and qRT-PCR were used to determine the expression of osteogenesis-related genes (Runx2, OPN, OCN). ALP and Alizarin Red S staining were performed to evaluate osteogenic differentiation. The interactions between circ_0134944 and miR-127-5p, miR-127-5p and PDX1, PDX1 and SPHK1 were determined by dual-luciferase reporter and ChIP assay. Results: Circ_0134944, PDX1 and SPHK1 were upregulated while miR-127-5p was downregulated in PMOP patients. Enhanced expression of circ_0134944 suppressed osteogenesis, which was then reversed by miR-127-5p overexpression. The binding between circ_0134944 and miR-127-5p, PDX1 and miR-127-5p were confirmed by dual-luciferase reporter assay. Moreover, PDX1 was enriched in the promoter region of SPHK1, and SPHK1 overexpression prevented the promotion of osteogenesis induced by miR-127-5p overexpression. Conclusions: Taken together, these results demonstrate that circ_0134944 inhibit osteogenesis via miR-127-5p/PDX1/SPHK1 axis. Thus, the present study offered evidence that circ_0134944/miR-127-5p/PDX1/SPHK1 axis could be a potential therapeutic target for PMOP.

2.
Front Cardiovasc Med ; 8: 764038, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34782856

RESUMO

Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes degradation of low-density lipoprotein receptor (LDLR) and plays a central role in regulating plasma levels of LDL cholesterol levels, lipoprotein(a) and triglyceride-rich lipoproteins, increasing the risk of cardiovascular disease. Additionally, PCSK9 promotes degradation of major histocompatibility protein class I and reduces intratumoral infiltration of cytotoxic T cells. Inhibition of PCSK9 increases expression of LDLR, thereby reducing plasma levels of lipoproteins and the risk of cardiovascular disease. PCSK9 inhibition also increases cell surface levels of major histocompatibility protein class I in cancer cells and suppresses tumor growth. Therefore, PCSK9 plays a vital role in the pathogenesis of cardiovascular disease and cancer, the top two causes of morbidity and mortality worldwide. Monoclonal anti-PCSK9 antibody-based therapy is currently the only available treatment that can effectively reduce plasma LDL-C levels and suppress tumor growth. However, high expenses limit their widespread use. PCSK9 promotes lysosomal degradation of its substrates, but the detailed molecular mechanism by which PCSK9 promotes degradation of its substrates is not completely understood, impeding the development of more cost-effective alternative strategies to inhibit PCSK9. Here, we review our current understanding of PCSK9 and focus on the regulation of its expression and functions.

3.
Adv Healthc Mater ; : e2102038, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34729950

RESUMO

Glutamine metabolism of tumor cells plays a crucial role in maintaining cell homeostasis and reducing oxidative damage. Herein, a valid strategy of inhibiting glutamine metabolism is proposed to amplify the oxidative damage of photodynamic therapy (PDT) to tumor cells. Specifically, the authors develop a drug co-delivery system (designated as CeV) based on chlorine e6 (Ce6) and V9302 via the self-assembly technology. In spite of the strong hydrophobicity of therapeutic agents, the assembled CeV holds a favorable dispersibility in water and an improved cellular uptake capability. Under light irradiation, the internalized CeV is capable of generating abundant reactive oxygen species (ROS) for PDT. More importantly, CeV can reduce the uptake of glutamine through V9302-mediated alanine-serine-cysteine transporter of type-2 (ASCT2) inhibition, leading to a reduced glutathione (GSH) production and an amplified oxidative stress. As a result, CeV has a robust PDT efficacy on tumor inhibition by the blockade of glutamine transport. Notably, CeV exhibits a superiority on tumor suppression over the single treatment as well as the combined administration of Ce6 and V9302, which indicates the advantage of CeV for synergistic treatment. It may serve as a novel nanoplatform for developing a drug co-delivery system to improve PDT efficiency by inhibiting cell metabolism.

4.
Mater Horiz ; 2021 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-34698756

RESUMO

Planar chiral organic fluorescent materials that exhibit high chiral stability, high efficiency and circularly polarized luminescence (CPL) currently remain an unresolved issue despite their promising applications in optical encryption and 3D-display. Herein, a pair of new donor-chiral π-acceptor (D-π*-A) type planar chiral thermally activated delayed fluorescence (TADF) enantiomers, namely R/S-PXZ-PT, are developed. Such a D-π*-A type structure completely suppresses the racemisation of the planar chirality, making it possible to prepare circularly polarized organic light-emitting diodes (CP-OLEDs) by vacuum deposition processing. Moreover, this design perfectly integrates the chiral unit into the luminescent unit to achieve intense CPL activity with luminescence asymmetry factors (glum) of ±1.9 × 10-3. Notably, the enantiomer-based devices exhibit a yellow coloured emission with a maximum external quantum efficiency (EQE) of 20.1%, and mirror-image circularly polarized electroluminescence signals with electroluminescence dissymmetry factors (gEL) of +1.5 × 10-3/-1.3 × 10-3. This work not only enriches the diversity of chiral TADF molecular design, but also provides a new perspective for the development of highly-efficient CP-OLEDs with stable planar chiral TADF materials.

5.
ISA Trans ; 2021 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-34689961

RESUMO

This study considers the coordinated control for quasilinear multiagent systems (QMASs). An output feedback predictive control (OFPC) strategy is given to implement both coordination and simultaneous stability and output consensus (SSOC). In the OFPC strategy, a cost function aiming at coordination relationship is minimized by predictive control thus coordination among QMASs is implemented. Further discussion derives a criterion to maintain the closed-loop QMASs realize the SSOC. Finally, two examples are proposed to richly illustrate the availability of the OPFC strategy.

6.
J Mol Cell Biol ; 13(7): 513-526, 2021 10 21.
Artigo em Inglês | MEDLINE | ID: mdl-34297054

RESUMO

Lipids exert many essential physiological functions, such as serving as a structural component of biological membranes, storing energy, and regulating cell signal transduction. Dysregulation of lipid metabolism can lead to dyslipidemia related to various human diseases, such as obesity, diabetes, and cardiovascular disease. Therefore, lipid metabolism is strictly regulated through multiple mechanisms at different levels, including the extracellular matrix. Membrane-type I matrix metalloproteinase (MT1-MMP), a zinc-dependent endopeptidase, proteolytically cleaves extracellular matrix components, and non-matrix proteins, thereby regulating many physiological and pathophysiological processes. Emerging evidence supports the vital role of MT1-MMP in lipid metabolism. For example, MT1-MMP mediates ectodomain shedding of low-density lipoprotein receptor and increases plasma low-density lipoprotein cholesterol levels and the development of atherosclerosis. It also increases the vulnerability of atherosclerotic plaque by promoting collagen cleavage. Furthermore, it can cleave the extracellular matrix of adipocytes, affecting adipogenesis and the development of obesity. Therefore, the activity of MT1-MMP is strictly regulated by multiple mechanisms, such as autocatalytic cleavage, endocytosis and exocytosis, and post-translational modifications. Here, we summarize the latest advances in MT1-MMP, mainly focusing on its role in lipid metabolism, the molecular mechanisms regulating the function and expression of MT1-MMP, and their pharmacotherapeutic implications.

7.
Front Hum Neurosci ; 15: 698367, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305556

RESUMO

Spatial cognitive abilities, including mental rotation (MR) and visuo-spatial working memory (vsWM) are correlated with mathematical performance, and several studies have shown that training of these abilities can enhance mathematical performance. Here, we investigated the behavioral and neural correlates of MR and vsWM training combined with number line (NL) training. Fifty-seven children, aged 6-7, performed 25 days of NL training combined with either vsWM or MR and participated in an Electroencephalography (EEG)-session in school to measure resting state activity and steady-state visual evoked potentials during a vsWM task before and after training. Fifty children, aged 6-7, received usual teaching and acted as a control group. Compared to the control group, both training groups improved on a combined measure of mathematics. Cognitive improvement was specific to the training. Significant pre-post changes in resting state-EEG (rs-EEG), common to both training groups, were found for power as well as for coherence, with no significant differences in rs-EEG-changes between the vsWM and MR groups. Two of the common rs-EEG changes were correlated with mathematical improvement: (1) an increase in coherence between the central frontal lobe and the right parietal lobe in frequencies ranging from 16 to 25 Hz, and (2) an increase in coherence between the left frontal lobe and the right parietal lobe ranging from 23 to 25 Hz. These results indicate that changes in fronto-parietal coherence are related to an increase in mathematical performance, which thus might be a useful measure in further investigations of mathematical interventions in children.

8.
J Lipid Res ; 62: 100091, 2021 Jun 09.
Artigo em Inglês | MEDLINE | ID: mdl-34118252

RESUMO

Plasma LDL is produced from catabolism of VLDL and cleared from circulation mainly via the hepatic LDL receptor (LDLR). Proprotein convertase subtilisin/kexin type 9 (PCSK9) promotes LDLR degradation, increasing plasma LDL-C levels. Circulating PCSK9 is mainly secreted by the liver, whereas VLDL is exclusively secreted by hepatocytes. However, the mechanism regulating their secretion is not completely understood. Surfeit 4 (Surf4) is a cargo receptor localized in the ER membrane. It recruits cargos into coat protein complex II vesicles to facilitate their secretion. Here, we investigated the role of Surf4 in VLDL and PCSK9 secretion. We generated Surf4 liver-specific knockout mice and found that knockout of Surf4 did not affect PCSK9 secretion, whereas it significantly reduced plasma levels of cholesterol, triglyceride, and lipid-binding protein apolipoprotein B (apoB). In cultured human hepatocytes, Surf4 coimmunoprecipitated and colocalized with apolipoprotein B100, and Surf4 silencing reduced secretion of apolipoprotein B100. Furthermore, knockdown of Surf4 in LDLR knockout (Ldlr-/-) mice significantly reduced triglyceride secretion, plasma levels of apoB and non-HDL-C, and the development of atherosclerosis. However, Surf4 liver-specific knockout mice and Surf4 knockdown in Ldlr-/- mice displayed similar levels of liver lipids and plasma alanine aminotransferase activity as control mice, indicating that inhibition of Surf4 does not cause notable liver damage. Expression of stearoyl-CoA desaturase-1 was also reduced in the liver of these mice, suggesting a reduction in de novo lipogenesis. In summary, hepatic deficiency of Surf4 reduced VLDL secretion and the development of atherosclerosis but did not cause significant hepatic lipid accumulation or liver damage.

9.
Angew Chem Int Ed Engl ; 60(28): 15291-15295, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-33955656

RESUMO

The design and synthesis of nitrogen-doped aromatic belts with conjugated structures still remain a challenge. Here, we report the first nitrogen-doped aromatic belt with a [6]cycloparaphenylene skeleton, which is conveniently synthesized from the easily available calix[3]carbazole. The aromatic belt has a rigid conjugated structure and deep cavity, and it can encapsulate one dichloromethane both in solution and in the solid state. Interestingly, the aromatic belt shows strong green fluorescence with a quantum yield of 0.39 and exhibits a narrow HOMO-LUMO energy gap of 2.02 eV. The belt-shaped conjugated structure composed of three carbazole subunits has specific optoelectronic properties that will promote wide applications in supramolecular chemistry and materials science.

10.
Biomaterials ; 273: 120854, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33932703

RESUMO

The development of photodynamic therapy (PDT) is severely limited by short half-life of singlet oxygen (1O2) and the hypoxic microenvironment. In this work, a plasma membrane targeted photodynamic O2 economizer (designated as P-POE) is developed to improve the subcellular delivery of photosensitizers and alleviate the tumor hypoxia for enhanced PDT effect. After self-assembly into nanomicelles, P-POE has a relatively high stability and a favorable photochemical performance, which are conducive to boosting the 1O2 production. Besides, the plasma membrane anchoring of P-POE contributes to enhancing the preferential retention and cellular accumulation of photosensitizers on tumor tissues and cells. More importantly, P-POE-induced mitochondrial respiratory depression is demonstrated to reduce the O2 consumption of tumor cells to relieve the hypoxia. Consequently, P-POE still exhibits a robust PDT effect against hypoxic tumors, which greatly inhibits the proliferation of breast cancer with low adverse reactions. This innovative combination of subcellular targeting and hypoxic alleviation would advance the development of individualized drug delivery systems for photodynamic therapy against hypoxic tumors.


Assuntos
Nanopartículas , Fotoquimioterapia , Linhagem Celular Tumoral , Membrana Celular , Humanos , Hipóxia/tratamento farmacológico , Oxigênio , Fármacos Fotossensibilizantes/uso terapêutico
11.
Adv Healthc Mater ; 10(12): e2100198, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33938637

RESUMO

Photodynamic therapy (PDT) often suffers from the exacerbated tumor hypoxia and the heterogeneous distribution of photosensitizers, leading to an inefficient ROS productivity and availability. In this work, a mitochondria targeted O2 economizer (designated as Mito-OxE) is developed to improve PDT efficiency by alleviating tumor hypoxia and enhancing the subcellular localization of photosensitizers. Specifically, the photosensitizer of protoporphyrin IX (PpIX) is modified with the hydrophilic polyethylene glycol and the lipophilic cation of triphenylphosphine (TPP) to fabricate the biocompatible mitochondria targeted photosensitizers (designated as Mito-PSs). And Mito-OxE is prepared by using Mito-PSs to load the mitochondrial oxidative phosphorylation inhibitors of atovaquone (ATO). Benefiting from the targeting capability of TPP, Mito-OxE can selectively accumulate in mitochondria after cellular uptake. Subsequently, the mitochondrial respiration would be suppressed to with the participation of ATO, resulting in a local hypoxia mitigation for enhanced PDT. Compared with Mito-PSs, Mito-OxE maximizes the therapeutic effect against hypoxic tumors under light irradiation. This design of mitochondria targeted O2 economizer would advance the development of targeted drug delivery system for effective PDT regardless of hypoxic microenvironment.


Assuntos
Nanopartículas , Fotoquimioterapia , Linhagem Celular Tumoral , Humanos , Hipóxia/metabolismo , Mitocôndrias/metabolismo , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico , Hipóxia Tumoral
13.
Nat Commun ; 12(1): 1889, 2021 03 25.
Artigo em Inglês | MEDLINE | ID: mdl-33767172

RESUMO

Plasma low-density lipoprotein (LDL) is primarily cleared by LDL receptor (LDLR). LDLR can be proteolytically cleaved to release its soluble ectodomain (sLDLR) into extracellular milieu. However, the proteinase responsible for LDLR cleavage is unknown. Here we report that membrane type 1-matrix metalloproteinase (MT1-MMP) co-immunoprecipitates and co-localizes with LDLR and promotes LDLR cleavage. Plasma sLDLR and cholesterol levels are reduced while hepatic LDLR is increased in mice lacking hepatic MT1-MMP. Opposite effects are observed when MT1-MMP is overexpressed. MT1-MMP overexpression significantly increases atherosclerotic lesions, while MT1-MMP knockdown significantly reduces cholesteryl ester accumulation in the aortas of apolipoprotein E (apoE) knockout mice. Furthermore, sLDLR is associated with apoB and apoE-containing lipoproteins in mouse and human plasma. Plasma levels of sLDLR are significantly increased in subjects with high plasma LDL cholesterol levels. Thus, we demonstrate that MT1-MMP promotes ectodomain shedding of hepatic LDLR, thereby regulating plasma cholesterol levels and the development of atherosclerosis.


Assuntos
Apolipoproteína B-100/sangue , Apolipoproteínas E/sangue , Aterosclerose/patologia , Lipoproteínas LDL/sangue , Metaloproteinase 14 da Matriz/metabolismo , Receptores de LDL/metabolismo , Animais , Apolipoproteínas E/genética , Linhagem Celular Tumoral , Ésteres do Colesterol/metabolismo , Dependovirus/genética , Feminino , Células HEK293 , Células Hep G2 , Humanos , Masculino , Metaloproteinase 14 da Matriz/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
14.
Trials ; 22(1): 215, 2021 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-33736678

RESUMO

BACKGROUND: Hemiplegia is a common sequela after stroke, and acupuncture is one of the most common physical therapies used to treat hemiplegia during the recovery stage after ischaemic stroke. 'Hand and foot acupuncture with twelve needles' is an acupuncture treatment performed after stroke. The principal objective of this study is to assess the efficacy and safety of 'hand and foot acupuncture with twelve needles' for hemiplegia in the convalescent stage of ischaemic stroke. METHODS: This is the protocol for a randomised, controlled clinical trial with two groups: a 'hand and foot acupuncture with twelve needles' group and a routine acupuncture group. A total of 208 participants will be randomly assigned to two different groups in a 1:1 ratio and will undergo conventional rehabilitation. Limb function will be evaluated by the simplified Fugl-Meyer assessment scale, Barthel Index, modified Ashworth scale and National Institute of Health stroke scale. The participants will be evaluated at baseline (on the day of enrolment) and followed up at 2 weeks, 1 month, 2 months and 3 months after enrolment. DISCUSSION: The results of this study will provide evidence on the effectiveness of 'hand and foot acupuncture with twelve needles' in the treatment of limb dysfunction that can be used for future evaluations. TRIAL REGISTRATION: Chictr.org.cn ChiCTR1900021774 . Registered on 8 March 2019.


Assuntos
Terapia por Acupuntura , Isquemia Encefálica , AVC Isquêmico , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Terapia por Acupuntura/efeitos adversos , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Hemiplegia/diagnóstico , Hemiplegia/etiologia , Hemiplegia/terapia , Humanos , Agulhas , Qi , Ensaios Clínicos Controlados Aleatórios como Assunto , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Resultado do Tratamento
15.
Angew Chem Int Ed Engl ; 60(23): 13021-13028, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33783080

RESUMO

An approach to the highly efficient synthesis of C(sp3)-bridged [6]cycloparaphenylenes (C[6]CPPs) from fluoren[3]arenes (F[3]As) was developed. Consequently, F[3]As as a new kind of macrocyclic arenes were synthesized. Followed by the demethylation, triflation and intramolecular aryl-aryl coupling reactions, C[6]CPPs were then conveniently obtained. Interestingly, C[6]CPPs could be selectively methylated to produce their fully outer-methyl-substituted derivatives. The crystal structures showed the hydroxyl-substituted F[3]As had bowl-shaped conformations, and the C[6]CPPs exhibited rigid belt-shaped structures with deep cavities. Moreover, C[6]CPPs exhibited high HOMO energies and narrow energy gaps. An unclosed belt was further obtained, and it not only showed a similar narrow energy gap to those of the aromatic belts, but also displayed strong fluorescence property, which can play a vital role in the design and synthesis of new aromatic belts.

16.
Biol Psychol ; 161: 108080, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33744372

RESUMO

INTRODUCTION: We developed a neurocognitive assessment tool (NCAT) in consultation with mental health professionals working with children with AD/HD as a diagnostic aid and screening tool. This study examines the predictive utility of NCAT in the classification of children with AD/HD Inattentive presentation. METHOD: Fifty three children with AD/HD Inattentive presentation and 161 typically-developing children completed an NCAT assessment. Discriminant function analyses examined group membership prediction for separate components of NCAT and for the components combined. RESULTS: The combined model correctly classified 93.4 % of participants, with 91.4 % sensitivity and 93.9 % specificity. Contributions to classification were from SNAP-IV, psychological needs satisfaction, self-regulation, executive function performance, and EEG. The combined model resulted in a 9.3 % increase in specificity and 5.9 % increase in sensitivity compared to SNAP-IV alone. CONCLUSIONS: NCAT provides good discrimination between children with and without AD/HD of the Inattentive presentation, and further investigation including other subtypes and comorbidities is warranted.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Mapeamento Encefálico , Criança , Cognição , Eletroencefalografia , Função Executiva , Humanos
17.
NPJ Biofilms Microbiomes ; 7(1): 6, 2021 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-33479252

RESUMO

The process of microbiologically influenced corrosion (MIC) in soils has received widespread attention. Herein, long-term outdoor soil burial experiments were conducted to elucidate the community composition and functional interaction of soil microorganisms associated with metal corrosion. The results indicated that iron-oxidizing (e.g., Gallionella), nitrifying (e.g., Nitrospira), and denitrifying (e.g., Hydrogenophaga) microorganisms were significantly enriched in response to metal corrosion and were positively correlated with the metal mass loss. Corrosion process may promote the preferential growth of the abundant microbes. The functional annotation revealed that the metabolic processes of nitrogen cycling and electron transfer pathways were strengthened, and also that the corrosion of metals in soil was closely associated with the biogeochemical cycling of iron and nitrogen elements and extracellular electron transfer. Niche disturbance of microbial communities induced by the buried metals facilitated the synergetic effect of the major MIC participants. The co-occurrence network analysis suggested possible niche correlations among corrosion related bioindicators.


Assuntos
Microbiota , Microbiologia do Solo , Aço/química , Bactérias/classificação , Bactérias/crescimento & desenvolvimento , Bactérias/isolamento & purificação , Bactérias/metabolismo , Corrosão , Transporte de Elétrons , Biomarcadores Ambientais , Ferro/metabolismo , Nitrogênio/metabolismo , Solo/química
18.
Clin Infect Dis ; 73(9): e3324-e3332, 2021 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33395488

RESUMO

BACKGROUND: Few safety and effectiveness results have been published regarding the administration of tenofovir alafenamide fumarate (TAF) during pregnancy for the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). METHODS: In this multicenter prospective observational study, pregnant women with HBV DNA levels higher than 200 000 IU/mL who received TAF or tenofovir disoproxil fumarate (TDF) from gestational weeks 24-35 to delivery were 1:1 enrolled and followed until postpartum month 6. Infants received immunoprophylaxis. The primary endpoint was the safety of mothers and infants. The secondary endpoint was the hepatitis B surface antigen (HBsAg)-positive rate at 7 months for infants. RESULTS: In total, 116 and 116 mothers were enrolled, and 117 and 116 infants were born, in the TAF and TDF groups, respectively. TAF was well tolerated during a mean treatment duration of 11.0 weeks. The most common maternal adverse event was nausea (19.0%). One (0.9%), 3 (2.6%), and 9 (7.8%) mothers had abnormal alanine aminotransferase levels at delivery and at postpartum months 3 and 6, respectively. The TDF group had safety profiles that were comparable to those of the TAF group. No infants had birth defects in either group. The infants' physical and neurological development at birth and at 7 months in the TAF group were comparable with those in the TDF group. The HBsAg positive rate was 0% at 7 months in all 233 infants. CONCLUSIONS: Antiviral prophylaxis with TAF was determined to be generally safe for both mothers and infants and reduced the MTCT rate to 0%.


Assuntos
Hepatite B Crônica , Hepatite B , Complicações Infecciosas na Gravidez , Alanina , Antivirais/efeitos adversos , Feminino , Hepatite B/tratamento farmacológico , Hepatite B/prevenção & controle , Hepatite B Crônica/tratamento farmacológico , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/prevenção & controle , Estudos Prospectivos , Tenofovir/análogos & derivados , Carga Viral
19.
J Cardiovasc Pharmacol ; 77(2): 217-227, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33165140

RESUMO

ABSTRACT: Lipid metabolism disorder and inflammatory response are considered to be the major causes of atherosclerogenesis. Astragalin, the most important functional component of flavonoid obtained from persimmon leaves, has the hypolipidemic effects. However, it is unknown, how astragalin protects against atherosclerosis. The aim of this study was to observe the effects of astragalin on cholesterol efflux and inflammatory response and to explore the underlying mechanisms. Our results showed that astragalin upregulated the expression of ATP-binding cassette transporters A1 and G1 (ABCA1 and ABCG1), promoted cholesterol efflux, and suppressed foam cell formation. Inhibition of the PPARγ/LXRα pathway abrogated the promotive effects of astragalin on both transporter expression and cholesterol efflux. In addition, treatment of astragalin markedly decreased the secretion of inflammatory factors, including interleukin 6, monocyte chemotactic protein 1, tumor necrosis factor α, and interleukin 1ß. Mechanistically, astragalin upregulated ABCA1 and ABCG1 expression, which in turn reduced TLR4 surface levels and inhibited NF-κB nuclear translocation. Consistently, astragalin reduced atherosclerotic plaque area in apoE-/- mice. Taken together, these findings suggest that astragalin protects against atherosclerosis by promoting ABCA1- and ABCG1-mediated cholesterol efflux and inhibiting proinflammatory mediator release.

20.
J Atten Disord ; 25(3): 414-431, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-30265176

RESUMO

Objective: This preliminary study investigated effectiveness of neurocognitive training on academic engagement (AET) for children with ADHD. The training approach targeted working memory, inhibitory control, and attention/relaxation (via brain electrical activity). Method: A reversal design with a 2-week follow-up was used to assess the effectiveness of the treatment on two children with diagnosed ADHD in two learning settings. Direct observation was used to collect academic-related behavior. Results: Improvements in on-task expected behavior (ONT-EX) and general AET, as well as reductions in off-task motor activity (OFF-MA) and off-task passive behavior (OFF-PB) were observed for both students over baselines and across the settings. Moreover, differences in behavioral change were found between participants and settings. Conclusion: These findings support using the treatment for improving academic performance of children with ADHD. Future studies may investigate influences of contextual differences, nontreatment variables, or adult's feedback during the training session on treatment effectiveness.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Neurorretroalimentação , Atenção , Transtorno do Deficit de Atenção com Hiperatividade/terapia , Criança , Humanos , Aprendizagem , Memória de Curto Prazo , Resultado do Tratamento
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