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1.
J Med Virol ; 96(4): e29618, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38639293

RESUMO

Human adenovirus (HAdV) is a significant viral pathogen causing severe acute respiratory infections (SARIs) in children. To improve the understanding of type distribution and viral genetic characterization of HAdV in severe cases, this study enrolled 3404 pediatric SARI cases from eight provinces of China spanning 2017-2021, resulting in the acquisition of 112 HAdV strains. HAdV-type identification, based on three target genes (penton base, hexon, and fiber), confirmed the diversity of HAdV types in SARI cases. Twelve types were identified, including species B (HAdV-3, 7, 55), species C (HAdV-1, 2, 6, 89, 108, P89H5F5, Px1/Ps3H1F1, Px1/Ps3H5F5), and E (HAdV-4). Among these, HAdV-3 exhibited the highest detection rate (44.6%), followed by HAdV-7 (19.6%), HAdV-1 (12.5%), and HAdV-108 (9.8%). All HAdV-3, 7, 55, 4 in this study belonged to dominant lineages circulating worldwide, and the sequences of the three genes demonstrated significant conservation and stability. Concerning HAdV-C, excluding the novel type Px1/Ps3H1F1 found in this study, the other seven types were detected both in China and abroad, with HAdV-1 and HAdV-108 considered the two main types of HAdV-C prevalent in China. Two recombinant strains, including P89H5F5 and Px1/Ps3H1F1, could cause SARI as a single pathogen, warranting close monitoring and investigation for potential public health implications. In conclusion, 5 years of SARI surveillance in China provided crucial insights into HAdV-associated respiratory infections among hospitalized pediatric patients.


Assuntos
Infecções por Adenovirus Humanos , Adenovírus Humanos , Infecções Respiratórias , Criança , Humanos , Adenovírus Humanos/genética , Análise de Sequência de DNA/métodos , Filogenia , Adenoviridae/genética , China/epidemiologia , Infecções Respiratórias/epidemiologia
2.
Inorg Chem ; 60(22): 17357-17363, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34704442

RESUMO

Bi3+/Te4+ co-doped Cs2SnCl6 with dual emission spectrum (i.e., 450 and 575 nm) was achieved by a modified solution method, which can overcome the phase separation in the previous method for Cs2SnCl6 crystal growth. The two emission peaks arising from the two dopants Bi3+ and Te4+ have distinct photoluminescence (PL) lifetimes. Thus, the control of dopant ratio or PL delay time will regulate the PL intensity ratio between 450 and 575 nm peaks leading to adjustable emission color. The energy transfer between the two emission centers, which is confirmed by the optical spectra and PL lifetime, has a critical distance around 7.8 nm with a maximum of 50% transfer efficiency. The Bi3+/Te4+ co-doped Cs2SnCl6 with superior stability in water and aqua regia was fabricated into a single-phase white light-emitting diode. In the meantime, various luminescent heterostructures were obtained by epitaxial Cs2SnCl6 crystal growth with different dopants, which can broaden the study of composition engineering in halide perovskites.

3.
ACS Appl Bio Mater ; 7(3): 1643-1655, 2024 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-38366996

RESUMO

Pathogens and pests pose significant threats to global crop productivity and plant immunity, necessitating urgent measures from researchers to prevent pathogen contamination and pest damage to crops. A natural plant-based antibacterial agent, eugenol (EUG), has demonstrated excellent antimicrobial and insect repellent capabilities, but the characteristics of volatilization and poor dissolution limit the practical application. The nanoization of pesticide formulations holds promise in the development of highly effective pesticides for antibacterial and insecticidal purposes. Herein, a eugenol-loaded nano delivery system (EUG@CMC-PGMA-CS) was synthesized using glycidyl methacrylate (GMA) as a functional monomer to connect carrier core structure carboxymethyl cellulose (CMC) with shell structure chitosan (CS), and EUG was encapsulated within the carrier. EUG@CMC-PGMA-CS demonstrated excellent leaf affinity, with minimum contact angles (CAs) of 37.83 and 70.52° on hydrophilic and hydrophobic vegetable leaf surfaces, respectively. Moreover, the maximum liquid holding capacity (LHC) of EUG@CMC-PGMA-CS on both hydrophilic and hydrophobic vegetable leaf surfaces demonstrates a noteworthy 55.24% enhancement compared to the LHC of pure EUG. The in vitro release curve of EUG@CMC-PGMA-CS exhibited an initial burst followed by stable sustained release. It is with satisfaction that the nano delivery system demonstrated exceptional antibacterial properties against S. aureus and satisfactory insecticidal efficacy against Spodoptera litura. The development of this eugenol-loaded nano delivery system holds significant potential for enhanced antibacterial and insect repellents in agriculture, paving the way for the application of volatile bioactive substances.


Assuntos
Eugenol , Repelentes de Insetos , Eugenol/farmacologia , Eugenol/química , Carboximetilcelulose Sódica/química , Sistemas de Liberação de Fármacos por Nanopartículas , Staphylococcus aureus , Antibacterianos/farmacologia
4.
Front Optoelectron ; 17(1): 6, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38374460

RESUMO

With the rapid development of white LEDs, the research of new and efficient white light emitting materials has attracted increasing attention. Zero dimensional (0D) organic-inorganic hybrid metal halide perovskites with superior luminescent property are promising candidates for LED application, due to their abundant and tailorable structure. Herein, [(CH3)3S]2SnCl6·H2O is synthesized as a host for dopant ions Bi3+ and Sb3+. The Sb3+ doped, or Bi3+/Sb3+ co-doped, [(CH3)3S]2SnCl6·H2O has a tunable optical emission spectrum by means of varying dopant ratio and excitation wavelength. As a result, we can achieve single-phase materials suitable for emission ranging from cold white light to warm white light. The intrinsic mechanism is examined in this work, to clarify the dopant effect on the optical properties. The high stability of title crystalline material, against water, oxygen and heat, makes it promising for further application.

5.
Body Image ; 45: 210-218, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36963336

RESUMO

Considerable evidence exists on the associations of celebrity worship with body dissatisfaction and disordered eating. However, relevant findings are confined to Western contexts and thinness-oriented body dissatisfaction and disordered eating. Consequently, the relationships of celebrity worship with muscularity-oriented body dissatisfaction and disordered eating are largely underexplored, especially in non-Western countries. Thus, the present study aimed to examine the relationships of celebrity worship with body dissatisfaction and disordered eating in China. A total of 593 young adult celebrity worshippers in China were recruited online. Correlation and mediation analyses were conducted. In contrast to previous findings, celebrity worship was not associated with thinness-oriented body dissatisfaction. However, significant associations were identified between celebrity worship and muscularity-oriented body dissatisfaction for men (r = 0.32, p < .001) and women (r = 0.26, p < .001), thinness-oriented disordered eating for men (r = 0.31, p < .001) and women (r = 0.37, p < .001), and muscularity-oriented disordered eating for men (r = 0.58, p < .001). Body image inflexibility mediated the associations between celebrity worship and disordered eating in men and women. Findings indicate that celebrity worship correlates positively with body dissatisfaction and disordered eating in Chinese young adults.


Assuntos
Insatisfação Corporal , Transtornos da Alimentação e da Ingestão de Alimentos , Masculino , Humanos , Adulto Jovem , Feminino , Imagem Corporal/psicologia , Magreza , Satisfação Pessoal
6.
Biomol Biomed ; 23(5): 825-837, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-36946337

RESUMO

Diabetic cardiomyopathy (DCM) is a serious complication and death cause of diabetes mellitus (DM). Recent cardiology studies suggest that spermidine (SPD) has cardioprotective effects. Here, we verified the hypothesis of SPD's protective effects on DCM. Therefore, db/db mice and primary neonatal mouse cardiomyocytes were used to observe the effects of SPD. Immunoblotting showed that ornithine decarboxylase (ODC) and SPD/spermine N1-acetyltransferase (SSAT) were downregulated and upregulated in the myocardium of db/db mice, respectively. We found that diabetic mice showed cardiac dysfunction in 12 weeks. Conversely, exogenous SPD could improve cardiac functions and reduce the deposition of collagens, myocardial damage, reactive oxygen species (ROS) levels, and endoplasmic reticulum stress (ERS) in diabetic mouse hearts. Our results also demonstrated that cardiomyocytes displayed ferroptosis and then activated Pannexin-1 expression, which resulted in the increase of the extracellular adenosine triphosphate (ATP). Subsequently, increased ATP as a paracrine molecule combined to purinergic receptor P2X7 to activate ERK1/2 signaling pathway in cardiomyocytes and activated NCOA4-mediated ferroptinophagy to promote lipid peroxidation and ferroptosis. Interestingly, SPD could reverse these molecular processes. Our findings indicate an important new mechanism for DCM and suggest that SPD has potential applicability to protect against deterioration of cardiac function with DCM.


Assuntos
Diabetes Mellitus Experimental , Cardiomiopatias Diabéticas , Ferroptose , Camundongos , Animais , Espermidina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Diabetes Mellitus Experimental/metabolismo , Estresse do Retículo Endoplasmático
7.
Research (Wash D C) ; 6: 0095, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37011265

RESUMO

The enzyme-mimicking catalytic activity of single-atom nanozymes has been widely used in tumor treatment. However, research on alleviating metabolic diseases, such as hyperglycemia, has not been reported. Herein, we found that the single-atom Ce-N4-C-(OH)2 (SACe-N4-C-(OH)2) nanozyme promoted glucose absorption in lysosomes, resulting in increased reactive oxygen species production in HepG2 cells. Furthermore, the SACe-N4-C-(OH)2 nanozyme initiated a cascade reaction involving superoxide dismutase-, oxidase-, catalase-, and peroxidase-like activity to overcome the limitations associated with the substrate and produce •OH, thus improving glucose intolerance and insulin resistance by increasing the phosphorylation of protein kinase B and glycogen synthase kinase 3ß, and the expression of glycogen synthase, promoting glycogen synthesis to improve glucose intolerance and insulin resistance in high-fat diet-induced hyperglycemic mice. Altogether, these results demonstrated that the novel nanozyme SACe-N4-C-(OH)2 alleviated the effects of hyperglycemia without evident toxicity, demonstrating its excellent clinical application potential.

8.
Infect Drug Resist ; 15: 1753-1765, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35431560

RESUMO

Introduction: This study was aimed to examine the clinical and epidemiological characteristics of sporotrichosis in China and specifically Jilin Province, which is one of the areas with the highest incidence worldwide, and to provide data support for the global prevalence of sporotrichosis. Methods: A total of 4969 cases of sporotrichosis diagnosed at the Second Hospital of Jilin University from January 1, 1990 to December 31, 2019 were collected. Results: In Jilin Province, the male-to-female ratio was 1:2, the average age at onset was 48 ± 1 years, and the average disease duration was 4.8 ± 2.7 months. The most susceptible individuals were farmers. Cases occurred more commonly in the winter and spring (71.5%) than in the summer and autumn (28.5%). The fixed type infection was more prevalent. Among the cases, 64.8% showed typical mycological changes, and 77.6% showed atypical pathological changes. Regarding the epidemiological characteristics of sporotrichosis in China, 6565 cases were retrieved from the literature from January 1, 2010 to December 31, 2019. Among them, the most affected area was Jilin Province, followed by Heilongjiang Province, and Liaoning Province. The male-to-female ratio was 1:1.46. The fixed type infection was the most common. A total of 241 strains were identified by molecular biotechnology; among these, 217 were identified as Sporothrix globosa and 24 were identified as S. schenckii sensu stricto. Discussion: The results add clarity to the clinical epidemiology of sporotrichosis in China and specifically Jilin Province. We believe these data will help improve the epidemiology knowledge of sporotrichosis worldwide.

9.
Chem Commun (Camb) ; 58(100): 13959-13962, 2022 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-36448575

RESUMO

The exploration of green C-H oxidation for the rapid construction of functional molecules, remains a permanent goal in synthetic chemistry. Herein, a traceless N-nitroso enabled oxidative Heck and amidation cascade was realized, leading to quinolinones that feature green oxidation and great functional group tolerance. The expedient construction of quinolinone containing pharmaceuticals including Flucarbril, Clostamide and Aripiprazole was achieved in a concise and environmentally friendly manner.


Assuntos
Quinolonas , Quinolonas/química , Catálise , Preparações Farmacêuticas , Oxirredução , Estresse Oxidativo
10.
Front Cardiovasc Med ; 9: 1022861, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36312255

RESUMO

Diabetic cardiomyopathy (DCM) is one of the most serious complications of diabetes. Recent cardiology studies suggest that spermine has a cardioprotective effect. Here, we used proteomic and metabolomic analyses to reveal the underlying research targets in a type II diabetic (T2D) mouse model treated with spermine. Left ventricular tissues from nine mice (Control group, three; T2D group, three; T2D+SP group, three) were excised and analyzed. Quantitative analysis of the global proteome and metabolome was performed using the 4D label-free technique and untargeted metabolomics, respectively, and differentially expressed proteins (DEPs) and metabolites were used to perform bioinformatic analyses. A total of 169 DEPs were identified in T2D/Control group, including 115 upregulated and 54 downregulated proteins. Furthermore, 16 DEPs were identified in T2D+SP/T2D group, where these DEPs were found highly enriched in the cellular, metabolic processes, biological regulation, response to stimulus, and immune system process. The results of association analysis between proteomics and metabolomics showed that SP could affect the production of 51 metabolites by regulating the expression of 16 DEPs in the T2D+SP/T2D group. We also found that PRKG1 was closely related to the expressions of 10 overlapping metabolites between db/db and SP-treated mice. Our findings provide insights into the underlying mechanisms for DCM and suggest the potential applicability of utilizing spermine on protecting against DCM-associated cardiac function deterioration.

11.
Front Pharmacol ; 13: 827782, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35444545

RESUMO

The Chinese medicinal herb Scutellaria barbata D. Don has antitumour effects and is used to treat liver cancer in the clinic. S. barbata polysaccharide (SBP), one of the main active components extracted from S. barbata D. Don, exhibits antitumour activity. However, there is still a lack of research on the extraction optimization, structural characterization, and anti-hepatoma activity of acidic polysaccharides from S. barbata D. Don. In this study, the optimal extraction conditions for SBP were determined by response surface methodology (RSM): the material-liquid ratio was 1:25, the extraction time was 2 h, and the extraction temperature was 90°C. Under these conditions, the average extraction efficiency was 3.85 ± 0.13%. Two water-soluble polysaccharides were isolated from S. barbata D. Don, namely, SBP-1A and SBP-2A, these homogeneous acidic polysaccharide components with average molecular weights of 1.15 × 105 Da and 1.4 × 105 Da, respectively, were obtained at high purity. The results showed that the monosaccharide constituents of the two components were fucose, galactosamine hydrochloride, rhamnose, arabinose, glucosamine hydrochloride, galactose, glucose, xylose, and mannose; the molar ratio of these constituents in SBP-1A was 0.6:0.3:0.6:30.6:3.3:38.4:16.1:8:1.4, and that in SBP-2A was 0.6:0.5:0.8:36.3:4.4:42.7:9.2:3.6:0.7. In addition, SBP-1A and SBP-2A contained uronic acid and ß-glucan, and the residue on the polysaccharide was mainly pyranose. The in vitro results showed that the anti-hepatoma activity of SBP-2A was better than that of SBP-1A and SBP. In addition, SBP-2A significantly enhanced HepG2 cell death, as cell viability was decreased, and SBP-2A induced HepG2 cell apoptosis and blocked the G1 phase. This phenomenon was coupled with the upregulated expression of P53 and Bax/Bcl-2 ratio, as well as the downregulated expression of the cell cycle-regulating protein cyclinD1, CDK4, and Bcl-2 in this study. Further analysis showed that 50 mg/kg SBP-2A inhibited the tumour growth in H22 tumour-bearing mice, with an average inhibition rate of 40.33%. Taken together, SBP-2A, isolated and purified from S. barbata showed good antitumour activity in vivo and in vitro, and SBP-2A may be a candidate drug for further evaluation in cancer prevention. This study provides insight for further research on the molecular mechanism of the anti-hepatoma activity of S. barbata polysaccharide.

12.
Neural Regen Res ; 17(2): 409-417, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34269217

RESUMO

Hydrogen exhibits the potential to treat Alzheimer's disease. Stereotactic injection has been previously used as an invasive method of administering active hydrogen, but this method has limitations in clinical practice. In this study, triple transgenic (3×Tg) Alzheimer's disease mice were treated with hydrogen-rich water for 7 months. The results showed that hydrogen-rich water prevented synaptic loss and neuronal death, inhibited senile plaques, and reduced hyperphosphorylated tau and neurofibrillary tangles in 3×Tg Alzheimer's disease mice. In addition, hydrogen-rich water improved brain energy metabolism disorders and intestinal flora imbalances and reduced inflammatory reactions. These findings suggest that hydrogen-rich water is an effective hydrogen donor that can treat Alzheimer's disease. This study was approved by the Animal Ethics and Welfare Committee of Shenzhen University, China (approval No. AEWC-20140615-002) on June 15, 2014.

13.
Biomed Res Int ; 2021: 2769689, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33490266

RESUMO

BACKGROUND: As the most aggressive type of skin cancer, cutaneous melanoma (CM) is experiencing a rapidly rising mortality in recent years. Exploring potential prognostic biomarkers or mechanisms of disease progression therefore has a great significance for CM. The purpose of this study was to identify genetic markers and prognostic performance of N6-methyladenosine (m6A) regulators in CM. METHOD: Gene expression profiles, copy number variation (CNV), and single nucleotide polymorphism (SNP) data of patients were obtained from The Cancer Genome Atlas (TCGA) database. RESULTS: Genomic variation and association analysis of gene expressions revealed a high degree of genomic variation in the presence of m6A-regulated genes. m6A patients with high-frequency genomic variants in the regulatory gene tended to develop a worse prognosis (p < 0.01). Unsupervised cluster analysis of the expression profiles of m6A-regulated genes identified three clinically distinct molecular subtypes, including degradation-enhanced subgroup and immune-enhanced subgroup, with significant prognostic differences (p = 0.046). A novel prognostic signature, which was established according to m6A-related characteristic genes identified through genome-wide expression spectrum, could effectively identify samples with poor prognosis and enhanced immune infiltration, and the effectiveness was also verified in the dataset of the chip. CONCLUSION: We identified genetic changes in the m6A regulatory gene in CM and related survival outcomes. The findings of this study provide new insights into the epigenetic understanding of m6A in CM.


Assuntos
Adenosina/análogos & derivados , Variações do Número de Cópias de DNA/genética , Melanoma/genética , Polimorfismo de Nucleotídeo Único/genética , Neoplasias Cutâneas/genética , Adenosina/genética , Adenosina/metabolismo , Progressão da Doença , Regulação Neoplásica da Expressão Gênica/genética , Genômica/métodos , Humanos , Melanoma/classificação , Melanoma/metabolismo , Melanoma/patologia , Neoplasias Cutâneas/classificação , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Transcriptoma/genética , Aprendizado de Máquina não Supervisionado
14.
Psychophysiology ; 58(10): e13894, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34227119

RESUMO

Human cognition is often biased. It is a fundamental question in psychology how cognitive bias is modulated in the human brain. Automatic action tendency is a typical cognitive bias. The dorsolateral prefrontal cortex (DLPFC) is a crucial area for processing various behavioral tasks. We investigated the functional role of DLPFC in the modulation of cognitive bias by testing the automatic action tendency during automatic and regulated behavioral tasks. Unilateral intermittent or continuous theta burst stimulation (excitatory iTBS or inhibitory cTBS) was used to manipulate the left or right DLPFC excitability and assess the changes in automatic action tendency during a manikin task. An approaching behavior with positive stimulus and avoiding behavior with negative stimulus were performed in an automatic task. An approaching behavior with negative stimulus and avoiding behavior with positive stimulus were performed in a regulated task. Reaction time was measured. We confirmed the automatic action tendency that reaction time for performing an automatic task was shorter than that for performing a regulated task. The automatic action tendency was enhanced after left DLPFC excitatory iTBS and was abolished after left DLPFC inhibitory cTBS stimulation. On the other hand, right DLPFC excitatory iTBS accelerated the avoiding behaviors and right DLPFC inhibitory cTBS accelerated approaching behaviors. The results suggest that left DLPFC modulates the automatic action tendency while the right DLPFC modulates the direction of behavioral tasks. We conclude that left DLPFC and right DLPFC are key nodes in modulating the cognitive bias while their functional roles are different.


Assuntos
Córtex Pré-Frontal Dorsolateral/fisiologia , Desempenho Psicomotor/fisiologia , Pensamento/fisiologia , Estimulação Magnética Transcraniana , Adulto , Feminino , Humanos , Masculino , Adulto Jovem
15.
World J Clin Cases ; 9(28): 8579-8586, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34754871

RESUMO

BACKGROUND: Infantile hemangiomas (IHs) are the most common childhood benign tumors, showing distinctive progression characteristics and outcomes. Due to the high demand for aesthetics among parents of IH babies, early intervention is critical in some cases. ß-Adrenergic blockers and corticosteroids are first-line medications for IHs, while itraconazole, an antifungal medicine, has shown positive results in recent years. CASE SUMMARY: In the present study, itraconazole was applied to treat two IH cases. The therapeutic course lasted 80-90 d, during which the visible lesion faded by more than 90%. Moreover, no obvious side effects were reported, and the compliance of the baby and parents was desirable. CONCLUSION: Although these outcomes further support itraconazole as an effective therapeutic choice for IHs, large-scale clinical and basic studies are still warranted to improve further treatment.

16.
Front Hum Neurosci ; 14: 202, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32581747

RESUMO

Background: The dorsolateral prefrontal cortex (DLPFC) in both hemispheres have a central integrative function for motor control and behavior. Understanding the hemispheric difference between DLPFC and ipsilateral motor cortex connection in the resting-state will provide fundamental knowledge to explain the different roles DLPFC plays in motor behavior. Purpose: The current study tested the interactions between the ipsilateral DLPFC and the primary motor cortex (M1) in each hemisphere at rest. We hypothesized that left DLPFC has a greater inhibitory effect on the ipsilateral M1 compared to the right DLPFC. Methods: Fourteen right-handed subjects were tested in a dual-coil paired-pulse paradigm using transcranial magnetic stimulation. The conditioning stimulus (CS) was applied to the DLPFC and the test stimulus (TS) was applied to M1. Interstimulus intervals (ISIs) between CS and TS were 2, 4, 6, 8, 10, 15, 20, 25, and 30 ms. The result was expressed as a percentage of the mean peak-to-peak amplitude of the unconditioned test pulse. Results: There was stronger inhibitory effect for the left compared to the right hemisphere at ISIs of 2 (p = 0.045), 10 (p = 0.006), 15 (p = 0.029) and 20 (p = 0.024) ms. There was no significant inhibition or facilitation at any ISI in the right hemisphere. Conclusions: The two hemispheres have distinct DLPFC and M1 cortico-cortical connectivity at rest. Left hemisphere DLPFC is dominant in inhibiting ipsilateral M1.

17.
J Exp Clin Cancer Res ; 39(1): 81, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381043

RESUMO

BACKGROUND: HER2-positive breast cancer is usually associated to the more aggressive progression and the worse prognosis, but the mechanism underlying the innate resistance to HER2-targeted therapy remains elusive. The scaffold protein SH3-domain-binding glutamic acid-rich protein-like protein (SH3BGRL) is indicated as a tumor suppressor in some cancers, but it is highly expressed in breast cancers. Here we characterized the tumorigenic function of SH3BGRL in HER2-expressing breast cancer cells and the subsequent effect in HER2-targeted therapies. METHODS: The interaction of SH3BGRL to HER2 were characterized with various truncated SH3BGRL mutants by immunoprecipitation and molecule docking simulation. The physiological roles of SH3BGRL interacting with HER2 in tumor progression and therapy implication were characterized by gain and loss of function approaches in vitro and in vivo. Immunohistochemistry was used for detections of SH3BGRL and p-HER2 (Y1196) expressions in xenografted tumors and human breast cancer tissues. Clinical relevance of SH3BGRL expression with HER2 was validated with both breast patient sample and the public data analyses. RESULTS: Our results demonstrated that SH3BGRL directly binds with HER2 on cell membrane via its motifs α1, α2 helixes and ß3 sheet, which postpones HER2 internalization upon EGF stimulation. Consequently, the association between SH3BGRL and HER2 contributed to the prolonged HER2 phosphorylation at specific tyrosine sites, especially at Y1196, and their downstream signaling activation. The relevance between SH3BGRL expression and p-HER2 (Y1196) phosphorylation was validated in both xenografted tumors and the breast cancer patient tissues. Mechanistically, SH3BGRL promoted breast tumor cell proliferation and survival, while reduced the cell sensitivity to anti-tumor drugs, especially to the HER2-targeted drugs. In contrast, Silencing SH3BGRL or inhibiting its downstream signals efficiently induced apoptosis of breast tumor cells with HER2 and SH3BGRL doubly positive expression. Database analysis also highlighted that SH3BGRL is a poor prognostic marker, especially for HER2-positive breast cancers. CONCLUSIONS: Our results disclose SH3BGRL as a novel posttranslational modulator of HER2 hyperactivation, which can lead to the intrinsic resistance to HER2-targeted therapy. SH3BGRL would be a pivotal therapy target and a diagnostic marker to HER2-positve patients. Thus, targeting SH3BGRL or the downstream signaling could relieve the innate resistance to some HER2-tageted therapies for both HER2 and SH3BGRL-postive breast cancers.


Assuntos
Neoplasias da Mama/genética , Membrana Celular/metabolismo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteínas/genética , Receptor ErbB-2/metabolismo , Animais , Neoplasias da Mama/patologia , Feminino , Humanos , Camundongos , Camundongos Nus , Transfecção
18.
Brain Behav ; 9(4): e01252, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30884212

RESUMO

BACKGROUND: Motor imagery (MI) improves motor skill learning, which is further enhanced when MI is paired with primary motor cortex transcranial brain stimulation or with electrical stimulation of the peripheral median nerve. Applying both stimulation types (here with 25 ms intervals) is called paired associative stimulation (PAS25). The final primary motor cortex output is determined by combined excitatory and intracortical inhibitory circuits, and reducing the latter is associated with enhanced synaptic transmission and efficacy. Indeed, short-interval intracortical inhibition (SICI) inhibits motor evoked potentials (MEPs), and motor learning has been associated with decreased SICI and increased cortical excitability. Here, we investigated whether cortical excitability and SICI are altered by PAS25 applied after MI-induced modulation of motor learning. METHODS: Peak acceleration of a hand-grasping movement and MEPs and SICI were measured before and after MI alone, PAS25 alone, and MI followed by PAS25 in 16 healthy participants to evaluate changes in motor learning, corticospinal excitability, and intracortical inhibition. RESULTS: After PAS25 alone, MEP amplitude increased while peak acceleration was unchanged. However, PAS25 applied following MI not only significantly enhanced both peak acceleration (p = 0.011) and MEP amplitude (p = 0.004) but also decreased SICI (p = 0.011). Moreover, we found that this decrease in SICI was significantly correlated with both the peak acceleration (r = 0.49, p = 0.029) and the MEP amplitude (r = 0.56, p = 0.013). CONCLUSIONS: These results indicate that brain function altered by PAS25 of the motor cortex enhances MI-induced motor learning and corticospinal excitability and decreases SICI, suggesting that SICI underlies, at least in part, PAS25 modulation of motor learning.


Assuntos
Potencial Evocado Motor/fisiologia , Imaginação/fisiologia , Aprendizagem/fisiologia , Destreza Motora/fisiologia , Desempenho Psicomotor/fisiologia , Estimulação Magnética Transcraniana/métodos , Adulto , Feminino , Humanos , Masculino , Córtex Motor/fisiologia , Movimento/fisiologia , Inibição Neural/fisiologia
19.
Talanta ; 154: 73-9, 2016 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-27154650

RESUMO

A chemiluminescent method for nitrite detection was developed on microfluidic chip. Carbon dots-NaNO2(-) acidified H2O2 system was adopted. Chemiluminescence (CL) spectrum of this system was detected. The radiative recombination of hole-injected and electron-injected carbon dots explained their CL property. Spiral microchannels were designed on the microfluidic chip to allow enough reaction time for the carbon dots-NaNO2-acidified H2O2 system. Carbon dots and NaNO2 were premixed in the branch microchannel, then, the mixture reacted with acidified H2O2 in spiral microchannels. Concentrations of H2SO4 and H2O2, dilution ratio of carbon dots in H2O and flow rate were optimized to obtain the best CL signals. The approach presented satisfactory linear relationship between NaNO2 concentration and CL intensity. The tolerance of metal ions in determination of 1×10(-5)M nitrite was analyzed. The nitrites in water and beverage samples were successfully analyzed on the microfluidic chip with good repeatability. The data were well accordance with the results obtained from GB 5009.33(-) 2010. This microfluidic CL detection method is believed to be a simple, automatic and agent-save approach for inorganic ion analysis.

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