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1.
Food Chem ; 450: 139338, 2024 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-38631210

RESUMO

The effect of ultrasonic intensity (28.14, 70.35, and 112.56 W/cm2) on Lignosus rhinocerotis polysaccharide (LRP) degraded by ultrasound assisted H2O2/Vc system (U-H/V) was investigated. U-H/V broke the molecular chain of LRP and improved the conformational flexibility, decreasing the molecular weight, intrinsic viscosity ([η]) and particle size. The functional groups and hyperbranched structure of LRP were almost stable after U-H/V treatment, however, the triple helix structure of LRP was partially disrupted. With increasing ultrasonic intensity, the critical aggregation concentration increased from 0.59 mg/mL to 1.57 mg/mL, and the hydrophobic microdomains reduced. Furthermore, the LRP treated with U-H/V significantly inhibited HepG2 cell proliferation by inducing apoptosis. The increase in antitumor activity of LRP was closely associated with the reduction of molecular weight, [η], particle size and hydrophobic microdomains. These results revealed that U-H/V treatment facilitates the degradation of LRP and provides a better insight into the structure-antitumor activity relationship of LRP.


Assuntos
Apoptose , Proliferação de Células , Peróxido de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Polissacarídeos , Polissacarídeos/química , Polissacarídeos/farmacologia , Humanos , Peróxido de Hidrogênio/química , Células Hep G2 , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Antineoplásicos/química , Antineoplásicos/farmacologia , Peso Molecular , Tamanho da Partícula , Gleiquênias/química , Ondas Ultrassônicas
2.
Am J Med Genet A ; : e63631, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38647383

RESUMO

Craniofacial microsomia (CFM), also known as the oculo-auriculo-vertebral spectrum, is a congenital disorder characterized by hypoplasia of the mandible and external ear due to tissue malformations originating from the first and second branchial arches. However, distinguishing it from other syndromes of branchial arch abnormalities is difficult, and causal variants remain unidentified in many cases. In this report, we performed an exome sequencing analysis of a Brazilian family with CFM. The proband was a 12-month-old boy with clinical findings consistent with the diagnostic criteria for CFM, including unilateral mandibular hypoplasia, microtia, and external auditory canal abnormalities. A heterozygous de novo nonsense variant (c.713C>G, p.S238*) in PUF60 was identified, which was predicted to be pathogenic in silico. PUF60 has been reported as a causal gene in Verheij syndrome, but not in CFM. Although the boy showed craniofacial abnormalities and developmental delay that overlapped with Verheij syndrome, the facial asymmetry with unilateral hypoplasia of the mandible observed in this case did not match the previously reported phenotypes of PUF60 variants. Our findings expand the phenotypic range of PUF60 variants that cover CFM and Verheij syndrome.

3.
Artigo em Inglês | MEDLINE | ID: mdl-38416620

RESUMO

Text-based person retrieval is the process of searching a massive visual resource library for images of a particular pedestrian, based on a textual query. Existing approaches often suffer from a problem of color (CLR) over-reliance, which can result in a suboptimal person retrieval performance by distracting the model from other important visual cues such as texture and structure information. To handle this problem, we propose a novel framework to Excavate All-round Information Beyond Color for the task of text-based person retrieval, which is therefore termed EAIBC. The EAIBC architecture includes four branches, namely an RGB branch, a grayscale (GRS) branch, a high-frequency (HFQ) branch, and a CLR branch. Furthermore, we introduce a mutual learning (ML) mechanism to facilitate communication and learning among the branches, enabling them to take full advantage of all-round information in an effective and balanced manner. We evaluate the proposed method on three benchmark datasets, including CUHK-PEDES, ICFG-PEDES, and RSTPReid. The experimental results demonstrate that EAIBC significantly outperforms existing methods and achieves state-of-the-art (SOTA) performance in supervised, weakly supervised, and cross-domain settings.

4.
Plant Biotechnol J ; 22(1): 98-115, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37688588

RESUMO

As a multifunctional hormone-like molecule, melatonin exhibits a pleiotropic role in plant salt stress tolerance. While actin cytoskeleton is essential to plant tolerance to salt stress, it is unclear if and how actin cytoskeleton participates in the melatonin-mediated alleviation of plant salt stress. Here, we report that melatonin alleviates salt stress damage in pigeon pea by activating a kinase-like protein, which interacts with an actin-depolymerizing factor. Cajanus cajan Actin-Depolymerizing Factor 9 (CcADF9) has the function of severing actin filaments and is highly expressed under salt stress. The CcADF9 overexpression lines (CcADF9-OE) showed a reduction of transgenic root length and an increased sensitivity to salt stress. By using CcADF9 as a bait to screen an Y2H library, we identified actin depolymerizing factor-related phosphokinase 1 (ARP1), a novel protein kinase that interacts with CcADF9. CcARP1, induced by melatonin, promotes salt resistance of pigeon pea through phosphorylating CcADF9, inhibiting its severing activity. The CcARP1 overexpression lines (CcARP1-OE) displayed an increased transgenic root length and resistance to salt stress, whereas CcARP1 RNA interference lines (CcARP1-RNAi) presented the opposite phenotype. Altogether, our findings reveal that melatonin-induced CcARP1 maintains F-actin dynamics balance by phosphorylating CcADF9, thereby promoting root growth and enhancing salt tolerance.


Assuntos
Cajanus , Melatonina , Melatonina/farmacologia , Melatonina/metabolismo , Actinas/metabolismo , Cajanus/genética , Destrina/metabolismo , Tolerância ao Sal/genética , Fosforilação , Citoesqueleto de Actina/metabolismo
5.
Plant Biotechnol J ; 22(1): 181-199, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37776153

RESUMO

Aluminium (Al) toxicity decreases crop production in acid soils in general, but many crops have evolved complex mechanisms to resist it. However, our current understanding of how plants cope with Al stress and perform Al resistance is still at the initial stage. In this study, the citrate transporter CcMATE35 was identified to be involved in Al stress response. The release of citrate was increased substantially in CcMATE35 over-expression (OE) lines under Al stress, indicating enhanced Al resistance. It was demonstrated that transcription factor CcNFYB3 regulated the expression of CcMATE35, promoting the release of citrate from roots to increase Al resistance in pigeon pea. We also found that a Long noncoding RNA Targeting Citrate Synthase (CcLTCS) is involved in Al resistance in pigeon pea. Compared with controls, overexpression of CcLTCS elevated the expression level of the Citrate Synthase gene (CcCS), leading to increases in root citrate level and citrate release, which forms another module to regulate Al resistance in pigeon pea. Simultaneous overexpression of CcNFYB3 and CcLTCS further increased Al resistance. Taken together, these findings suggest that the two modules, CcNFYB3-CcMATE35 and CcLTCS-CcCS, jointly regulate the efflux and synthesis of citrate and may play an important role in enhancing the resistance of pigeon pea under Al stress.


Assuntos
Cajanus , RNA Longo não Codificante , Ácido Cítrico/metabolismo , Cajanus/genética , Alumínio/toxicidade , Alumínio/metabolismo , Citrato (si)-Sintase , Citratos/metabolismo
6.
ACS Appl Bio Mater ; 7(1): 168-181, 2024 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-38109842

RESUMO

Reconstruction of critical sized bone defects in the oral and maxillofacial region continues to be clinically challenging despite the significant development of osteo-regenerative materials. Among 3D biomaterials, hydrogels and hydrogel composites have been explored for bone regeneration, however, their inferior clinical performance in comparison to autografts is mainly attributed to variable rates of degradation and lack of vascularization. In this study, we report hydrogel composite magnetic scaffolds formed from calcium carbonate, poly(vinyl alcohol) (PVA), and magnetic nanoparticles (MNPs), using PVA as matrix and calcium carbonate particles in vaterite phase as filler, to enhance the cross-linking of matrix and porosity with MNPs that can target and regulate cell signaling pathways to control cell behavior and improve the osteogenic and angiogenic potential. The physical and mechanical properties were evaluated, and cytocompatibility was investigated by culturing human osteoblast-like cells onto the scaffolds. The vaterite phase due to its higher solubility in comparison to calcium phosphates, combined with the freezing-thawing process of PVA, yielded porous scaffolds that exhibited adequate thermal stability, favorable water-absorbing capacity, excellent mineralization ability, and cytocompatibility. An increasing concentration from 1, 3, and 6 wt % MNPs in the scaffolds showed a statistically significant increase in compressive strength and modulus of the dry specimens that exhibited brittle fracture. However, the hydrated specimens were compressible and showed a slight decrease in compressive strength with 6% MNPs, although this value was higher compared to that of the scaffolds with no MNPs.


Assuntos
Engenharia Tecidual , Alicerces Teciduais , Humanos , Hidrogéis , Carbonato de Cálcio , Fenômenos Magnéticos
7.
Heliyon ; 9(10): e20643, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37829818

RESUMO

Objectives: This study sought to derive and validate a simple model combining traditional clinical risk factors with biomarkers and imaging indicators easily obtained from routine preoperative examinations to predict functionally significant coronary artery disease (CAD) in Chinese populations. Methods: We developed five models from a derivation cohort of 320 patients retrospective collected. In the derivation cohort, we assessed each model discrimination using the area under the receiver operating characteristic curve (AUC), reclassification using the integrated discrimination improvement (IDI) and net reclassification improvement (NRI), calibration using the Hosmer-Lemeshow test, and clinical benefit using decision curve analysis (DCA) to derive the optimal model. The optimal model was internally validated by bootstrapping, and external validation was performed in another cohort including 96 patients. Results: The optimal model including 5 predictors (age, sex, hyperlipidemia, hs-cTnI and LVEF) achieved an AUC of 0.807 with positive NRI and IDI in the derivation cohort. Moreover, the Hosmer-Lemeshow test showed a good fit, and the DCA demonstrated good clinical net benefit. The C-statistic calculated by bootstrapping internal validation was 0.798, and the calibration curve showed adequate calibration (Brier score = 0.179). In the external validation cohort, the optimal model performance was acceptable (AUC = 0.704; Brier score = 0.20). Finally, a nomogram based on this model was constructed to facilitate its use in clinical practice. Conclusions: A simple model combined clinical risk factors with hs-cTnI and LVEF improving the prediction of functionally significant CAD in Chinese populations. This attractive model may be a choice for clinicians to risk stratification for CAD.

9.
Acta Pharmacol Sin ; 44(12): 2492-2503, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37468692

RESUMO

Endothelial dysfunction, a central hallmark of cardiovascular pathogenesis in diabetes mellitus, is characterized by impaired endothelial nitric oxide synthase (eNOS) and NO bioavailability. However, the underlying mechanisms remain unclear. Here in this study, we aimed to identify the role of calmodulin (CaM) in diabetic eNOS dysfunction. Human umbilical vein endothelial cells and murine endothelial progenitor cells (EPCs) treated with high glucose (HG) exhibited downregulated CaM mRNA/protein and vascular endothelial growth factor (VEGF) expression with impeded eNOS phosphorylation and cell migration/tube formation. These perturbations were reduplicated in CALM1-knockdown cells but prevented in CALM1-overexpressing cells. EPCs from type 2 diabetes animals behaved similarly to HG-treated normal EPCs, which could be rescued by CALM1-gene transduction. Consistently, diabetic animals displayed impaired eNOS phosphorylation, endothelium-dependent dilation, and CaM expression in the aorta, as well as deficient physical interaction of CaM and eNOS in the gastrocnemius. Local CALM1 gene delivery into a diabetic mouse ischemic hindlimb improved the blunted limb blood perfusion and gastrocnemius angiogenesis, and foot injuries. Diabetic patients showed insufficient foot microvascular autoregulation, eNOS phosphorylation, and NO production with downregulated CaM expression in the arterial endothelium, and abnormal CALM1 transcription in genome-wide sequencing analysis. Therefore, our findings demonstrated that downregulated CaM expression is responsible for endothelium dysfunction and angiogenesis impairment in diabetes, and provided a novel mechanism and target to protect against diabetic endothelial injury.


Assuntos
Diabetes Mellitus Tipo 2 , Humanos , Camundongos , Animais , Diabetes Mellitus Tipo 2/metabolismo , Calmodulina/genética , Calmodulina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Endotélio/metabolismo , Isquemia/metabolismo , Óxido Nítrico Sintase Tipo III/genética , Óxido Nítrico Sintase Tipo III/metabolismo , Neovascularização Fisiológica
10.
Am J Hum Genet ; 110(7): 1068-1085, 2023 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-37352860

RESUMO

ERI1 is a 3'-to-5' exoribonuclease involved in RNA metabolic pathways including 5.8S rRNA processing and turnover of histone mRNAs. Its biological and medical significance remain unclear. Here, we uncover a phenotypic dichotomy associated with bi-allelic ERI1 variants by reporting eight affected individuals from seven unrelated families. A severe spondyloepimetaphyseal dysplasia (SEMD) was identified in five affected individuals with missense variants but not in those with bi-allelic null variants, who showed mild intellectual disability and digital anomalies. The ERI1 missense variants cause a loss of the exoribonuclease activity, leading to defective trimming of the 5.8S rRNA 3' end and a decreased degradation of replication-dependent histone mRNAs. Affected-individual-derived induced pluripotent stem cells (iPSCs) showed impaired in vitro chondrogenesis with downregulation of genes regulating skeletal patterning. Our study establishes an entity previously unreported in OMIM and provides a model showing a more severe effect of missense alleles than null alleles within recessive genotypes, suggesting a key role of ERI1-mediated RNA metabolism in human skeletal patterning and chondrogenesis.


Assuntos
Exorribonucleases , Histonas , Humanos , Exorribonucleases/genética , Histonas/genética , Mutação de Sentido Incorreto/genética , RNA Ribossômico 5,8S , RNA , RNA Mensageiro/genética
11.
Heliyon ; 9(5): e15879, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37215881

RESUMO

Background: Connexin 43 (Cx43), the predominant gap junction protein in hearts, is modified by specific (de)phosphorylation events under physiological and pathological states to affect myocardium function and structure. Previously we found that deficiency in Cx43 S282 phosphorylation could impair intercellular communication and contribute to cardiomyocyte apoptosis by activating p38 mitogen-activated protein kinase (p38 MAPK)/factor-associated suicide (Fas)/Fas-associating protein with a novel death domain (FADD) pathway, which is involved in myocardium injury in ischemia/reperfusion (I/R) heart. In addition, mutant at Cx43 S282 substituted with alanine heterozygous mice (S282A+/-) exhibited different degrees of ventricular arrhythmias and only some underwent myocardium apoptosis. In this study, we aimed to investigate the role of Cx43 pS282 in different cardiac pathological phenotypes. Methods: We examined cardiac function, structure, and relevant protein expression in S282A+/- mice (aged 2, 10 and 30 weeks) by electrocardiograph, echocardiography, histological staining, and co-immunoprecipitation followed by Western blot. Intraperitoneal isoprenaline injection and I/R surgery were applied in S282A+/- mice as external stimulus. 2,3,5-triphenyltetrazolium chloride staining was used for myocardium infarction evaluation. Results: Adult S282A+/- mice (aged 10 and 30 weeks) still exhibited spontaneous arrhythmia. Unlike neonatal stage (aged around 2 weeks), no apoptosis-related manifestations and the activation of p38 MAPK-Fas-FADD apoptotic pathway were observed in adult S282A+/- hearts. S282A+/- neonatal mice with cardiomyocytes apoptosis exhibited more than 60% dephosphorylation at Cx43 S282 than WT mice, while less than 40% S282 dephosphorylation were found in adult S282A+/- mice. In addition, although S282A+/- mice displayed normal cardiac function, they were highly susceptible to isoproterenol-induced ECG alternans and prone to cardiac injury and deaths upon I/R attack. Conclusions: These results reinforce that Cx43 S282 dephosphorylation acts as a susceptibility factor in regulating cardiomyocyte survival and cardiac electrical homeostasis in basal conditions and contributes to myocardium injury in the setting of I/R. Cx43 S282 phosphorylation was competent to induce spontaneous arrhythmias, cardiomyocyte apoptosis and deaths based on the degree of S282 dephosphorylation.

12.
Front Plant Sci ; 14: 1159181, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36993860

RESUMO

Microtubules are essential for regulating cell morphogenesis, plant growth, and the response of plants to abiotic stresses. TPX2 proteins are the main players determining the spatiotemporally dynamic nature of the MTs. However, how TPX2 members respond to abiotic stresses in poplar remains largely unknown. Herein, 19 TPX2 family members were identified from the poplar genome and analyzed the structural characteristics as well as gene expression patterns. All TPX2 members had the conserved structural characteristics, but exhibited different expression profiles in different tissues, indicating their varying roles during plant growth. Additionally, several light, hormone, and abiotic stress responsive cis-acting regulatory elements were detected on the promoters of PtTPX2 genes. Furthermore, expression analysis in various tissues of Populus trichocarpa showed that the PtTPX2 genes responded differently to heat, drought and salt stress. In summary, these results provide a comprehensive analysis for the TPX2 gene family in poplar and an effective contribution to revealing the mechanisms of PtTPX2 in the regulatory network of abiotic stress.

13.
Bone ; 167: 116603, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36343920

RESUMO

SLC4A2 belongs to the Na+-independent solute carrier family 4 (SLC4) of anion exchangers, which regulate electroneutral exchange of Cl- for HCO3- and mediate intra- and extra-cellular pH, chloride concentration and cell volume. Slc4a2 also participates in gastric acid secretion, spermatogenesis and osteoclastogenesis. During osteoclast differentiation, Slc4a2 is exclusively expressed at the contra-lacunar membrane and is up-regulated with osteoclast maturation. Bi-allelic Slc4a2 loss-of-function mutations have been known to cause osteopetrosis in mice and cattle, but not in human. Recently, we have identified bi-allelic pathogenic variants in SLC4A2 in a patient affected by osteopetrosis with severe renal insufficiency, suggesting SLC4A2 deficiency causes a new type of autosomal recessive osteopetrosis (osteopetrosis, Ikegawa type). In this article, we review the advances in exploring the multiple functions of SLC4A2 with emphasis on its roles in osteoclast. Our review would contribute to understanding of the phenotypic spectrum and the pathomechanism of SLC4A2-associated osteopetrosis.


Assuntos
Osteoclastos , Osteopetrose , Animais , Bovinos , Humanos , Masculino , Camundongos , Antiportadores de Cloreto-Bicarbonato/genética , Antiportadores de Cloreto-Bicarbonato/metabolismo , Mutação , Osteoclastos/metabolismo , Osteogênese , Osteopetrose/patologia
14.
Chem Biodivers ; 20(1): e202200900, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36404281

RESUMO

Four new xanthone glucosides, 3-hydroxy-2-methoxyxanthone-4-O-ß-D-glucopyranoside (1), 4,8-dihydroxy-2-methoxyxanthone-3-O-ß-D-glucopyranoside (2), 2-methoxyxanthone-5-O-ß-D-glucopyranoside (3), 4-hydroxy-2-methoxyxanthone-3-O-ß-D-glucopyranoside (4), a new phenolic acid, 4,4'-dihydroxy-3,3'-imino-di-benzoic acid monomethyl ester (5), and a new isoquinoline, methyl 6-hydroxy-1-oxo-1,2,3,4-tetrahydroisoquinoline-4-carboxylate (6) were isolated from the fruit of Hypericum patulum. The structural elucidation of the isolated compounds was primarily based on HR-ESI-MS, UV, IR, 1D and 2D NMR. All compounds were evaluated for their inhibitory effect against LPS-induced NO production in RAW 264.7 cells. Compound 2, 3 exhibited moderate inhibitory activity against NO production.


Assuntos
Hypericum , Hypericum/química , Frutas/química , Glucosídeos/química , Espectroscopia de Ressonância Magnética
15.
Annu Rev Food Sci Technol ; 14: 1-33, 2023 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-36400014

RESUMO

Edible nanoparticles are being developed for the oral delivery of nutrients to improve human health and well-being. Because of the extremely demanding conditions foods experience within the gastrointestinal tract, fundamental knowledge about the biological fate of encapsulated nutrients must be constantly revised. In this review, we first provide an overview of the fundamental absorption pathways of ingested foods and then discuss the evaluation models available to test and predict the biological fate of nutrient-loaded nanoparticles. Then, owing to their importance for human health, the impacts of nanoparticles on the gut microbiota are evaluated. Lastly, the limitations of current evaluation methods are highlighted and future research directions on the study and application of edible nanoparticles for the oral delivery of bioactive food compounds are discussed.


Assuntos
Microbioma Gastrointestinal , Nanopartículas , Humanos , Alimentos , Trato Gastrointestinal/metabolismo , Nutrientes
16.
Nat Prod Res ; : 1-6, 2022 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-36484645

RESUMO

A new naphthoquinone, patulumnaphthoquinone A (1) and three new glycosides, patulumside B (2), patulumside C (3) and patulumside D (4) were isolated from the 30% ethanol extract of the fresh ripe fruits of Hypericum patulum Thunb. using column chromatography techniques. The structures of these compounds including absolute configurations were elucidated on the basis of HRESIMS, NMR spectroscopic analyses, calculated electronic circular dichroism spectra and comparison with the literatures.

17.
Eur J Pharmacol ; 933: 175262, 2022 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-36100129

RESUMO

Among pulmonary arterial hypertension (PAH) patients, right ventricular (RV) functioning has been considered a major determining factor for cardiac capacity and survival. However, despite the recognition of the clinical importance for preserving RV functioning, no effective treatments are currently available for RV failure. This study aims to suggest one such possible treatment, through investigating the cardio-protective capabilities of the anti-oxidant, melatonin (Mel), for treating adverse RV remodeling in PAH, along with its underlying mechanisms. Arginine vasopressin induced neonatal rat cardiomyocyte hypertrophy in vitro; in vivo, PAH was induced in rats through intraperitoneal monocrotaline (MCT) injections, and Mel was administered intraperitoneally 24 h prior to MCT. Mel reduced rat cardiomyocyte hypertrophy and mitochondrial oxidative stress in vitro by activating the Mst1-Nrf2 pathway, which were all reversed upon siRNA knockdown of Mst1. Likewise, in vivo, Mel pre-treatment significantly ameliorated MCT-induced deterioration in cardiac function, RV hypertrophy, fibrosis and dilation. These beneficial effects were also associated with Mst1-Nrf2 pathway up regulation and its associated reduction in oxidative stress, as evidenced by the decrease in RV malondialdehyde content. Notably, results from Mel treatment were similar, or even superior, to those obtained from N-acetyl cysteine (NAC), which has already been-confirmed as an anti-oxidative treatment for PAH. By contrast, co-treatment with the Mst1 inhibitor XMU-MP-1 reversed all of those Mel-associated beneficial effects. Our findings thus identified Mel as a potent cardio-protective agent against the onset of maladaptive RV remodeling, through enhancement of the anti-oxidative response via Mst1-Nrf2 pathway activation.


Assuntos
Hipertensão Pulmonar , Melatonina , Hipertensão Arterial Pulmonar , Animais , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Arginina Vasopressina , Cisteína/uso terapêutico , Modelos Animais de Doenças , Hipertensão Pulmonar Primária Familiar , Fator de Crescimento de Hepatócito/metabolismo , Hipertensão Pulmonar/induzido quimicamente , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/tratamento farmacológico , Hipertrofia Ventricular Direita , Malondialdeído , Melatonina/farmacologia , Melatonina/uso terapêutico , Monocrotalina , Fator 2 Relacionado a NF-E2 , Proteínas Proto-Oncogênicas/metabolismo , Hipertensão Arterial Pulmonar/tratamento farmacológico , RNA Interferente Pequeno/uso terapêutico , Ratos , Remodelação Ventricular
18.
Int J Biochem Cell Biol ; 151: 106294, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36041701

RESUMO

AIMS: Angiogenesis plays a key role in coronary collateral circulation (CCC), the compensatory formation of new blood vessels during chronic total coronary occlusion. This study aimed to determine whether plasmacytoma variant translocation 1 (PVT1), a long non-coding (lnc) RNA involved in tumor angiogenesis, plays a role in regulating angiogenesis during chronic coronary ischemia. MAIN METHODS: Patients with coronary artery disease, and ≥ 90% stenosis, were examined and divided into "Good" and "Poor" CCC groups based on Rentrop Cohen classification. RNA samples were obtained from all patients, as well as from oxygen and glucose-deprived (OGD) HUVECs. PVT1, miR-15b-5p and AKT3 levels were measured with RT-qPCR or Western blot, while HUVEC migration and angiogenesis were detected by, respectively, wound-healing and tube formation assays. Luciferase reporter assay confirmed direct PVT1-miR-15b-5p binding. KEY FINDINGS: Increased PVT1 was found in "Good CCC" patient plasma, along with being highly expressed among OGD HUVECs; PVT1 knockdown reduced HUVEC migration, tube formation, and pro-angiogenic factor expression. Conversely, OGD HUVECs had downregulated miR-15b-5p, and miR-15b-5p overexpression significantly depressed their angiogenic capabilities. These PVT1 knockdown- or miR-15b-5p overexpression-associated reductions in angiogenic effects were reversed by AKT3 overexpression. In vivo, neovascularization and functioning in both ischemic mice hind-limbs and infarcted myocardium injected with ADV-sh-PVT1 were reduced, which were ameliorated by concurrent antagomiR-15b-5p injections. SIGNIFICANCE: Circulating PVT1 may serve as a useful biomarker to distinguish between good versus poor CCC, as it is involved in orchestrating angiogenesis via the miR-15b-5p-AKT3 axis; it thus has potential as a target for treating ischemic disease.


Assuntos
MicroRNAs , RNA Longo não Codificante/genética , Indutores da Angiogênese , Animais , Antagomirs , Artérias/metabolismo , Biomarcadores , Linhagem Celular Tumoral , Proliferação de Células/genética , Glucose , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Neovascularização Patológica/genética , Oxigênio , RNA Longo não Codificante/metabolismo
19.
BMC Med Educ ; 22(1): 484, 2022 Jun 22.
Artigo em Inglês | MEDLINE | ID: mdl-35733183

RESUMO

BACKGROUND: The aim of this study was to compare one-month acquisition and half-a-year quality retention of cardiopulmonary resuscitation (CPR) skills after initial training of medical students between peer videorecording feedback training (PVF) and traditional peer verbal feedback training (TVF). METHODS: Participants were randomly assigned to the PVF group (n = 62) and the TVF group (n = 65). All participants received a 45-min CPR training program performed by an American Heart Association basic life support-certified instructor, and then they began two hours of practice in groups. During interactive peer learning, students cooperated in couples of a doer and a helper to realize maximization of each other's learning. In the PVF group, training performance feedback came from peers based on practice videorecording. In the TVF group, feedback came from peers verbally without videorecording. CPR quality was tested at 1 and 6 months after training. RESULTS: After 1 month of initial training, the PVF group had a better presentation of CPR skills acquisition than the TVF group. Compared to the TVF group, the PVF group had significantly higher total scores, compression depth, appropriate compression depth, and complete chest recoil (p < 0.05). Moreover, compression interruption was a significantly positive change in the PVF group compared to the TVF group (p < 0.05). However, after 6 months, proportions of appropriate compression depth in the PVF group were better than those in the TVF group (p < 0.05). The differences in total scores, compression depth, appropriate compression depth, complete chest recoil and compression interruption were non-significant (all p > 0.05). CONCLUSIONS: Compared to TVF, PVF is more effective in enhancing CPR skill acquisition at 1 month. After half a year, CPR skill quality was obviously reduced in both groups, and no difference in CPR quality was found between the two groups.


Assuntos
Reanimação Cardiopulmonar , Estudantes de Medicina , Reanimação Cardiopulmonar/educação , Retroalimentação , Humanos , Manequins , Gravação em Vídeo
20.
iScience ; 25(5): 104220, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35494232

RESUMO

There has been growing interest in water-processable conjugated polymers for biocompatible devices. However, some broadly used conjugated polymers like poly(3-hexylthiophene) (P3HT) are hydrophobic and they cannot be processed in water. We herein report a facile yet highly efficient assembly method to prepare water-dispersible pyridine-containing P3HT (Py-P3HT) nanoparticles (NPs) with a high yield (>80%) and a fine size below 100 nm. It is based on the fast nanoprecipitation of Py-P3HT stabilized by hydrophilic poly(acrylic acid) (PAA). Py-P3HT can form spherical NPs at a concentration up to 0.2 mg/mL with a diameter of ∼75 nm at a very low concentration of PAA, e.g., 0.01-0.1 mg/mL, as surface ligands. Those negatively charged Py-P3HT NPs can bind with metal cations and further support the growth of noble metal NPs like Ag and Au. Our self-assembly methodology potentially opens new doors to process and directly use hydrophobic conjugated polymers in a much broader context.

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