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1.
FEBS Open Bio ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39054261

RESUMO

Although most cognitive impairments induced by prolonged alcohol consumption tend to improve within the initial months of abstinence, there is evidence suggesting certain cognitive deficits may persist. This study aimed to investigate the impact of aerobic exercise on learning and memory in alcohol use disorder (AUD) mice following a period of abstinence from alcohol. We also sought to assess the levels of monoamine neurotransmitters in the hippocampus. To this end, we established an AUD mouse model through a two-bottle choice (sucrose fading mode and normal mode) and chronic intermittent alcohol vapor (combined with intraperitoneal injection) and randomly allocated mice into exercise groups to undergo treadmill training. Learning and memory abilities were assessed through the Morris water maze test and spontaneous activity was evaluated using the open field test. The levels of dopamine, norepinephrine, serotonin, and brain-derived neurotrophic factor in the hippocampus were quantified using enzyme-linked immunoassay (ELISA) kits. The findings reveal that after cessation of alcohol consumption, learning and memory abilities in AUD mice did not completely return to normal levels. The observed enhancement of cognitive functions in AUD mice through aerobic exercise may be attributed to restoring levels of monoamine neurotransmitters in the hippocampus, boosting brain-derived neurotrophic factor (BDNF) concentrations, and facilitating an increase in hippocampal mass. These results offer empirical evidence to support aerobic exercise as a viable therapeutic strategy to alleviate cognitive deficits associated with AUD.

2.
Mol Immunol ; 171: 105-114, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38820902

RESUMO

Chlamydia trachomatis (CT) is the leading cause of bacterial sexually transmitted diseases worldwide, which can cause diseases such as pelvic inflammatory disease, and cervical and fallopian tube inflammation, and poses a threat to human health. Rosmarinic acid (RosA) is an active ingredient of natural products with anti-inflammatory and immunomodulatory effects. This study aimed to investigate the role of RosA in inhibiting autophagy-regulated immune cells-CD8+ T cells via the Ras/Raf/MEK/ERK signaling pathway in a CT-infected mouse model. Mice were inoculated with CT infection solution vaginally, and the mechanistic basis of RosA treatment was established using H&E staining, flow cytometry, immunofluorescence, transmission electron microscopy, and western blot. The key factors involved in RosA treatment were further validated using the MEK inhibitor cobimetinib. Experimental results showed that both RosA and the reference drug azithromycin could attenuate the pathological damage to the endometrium caused by CT infection; flow cytometry showed that peripheral blood CD8+ T cells increased after CT infection and decreased after treatment with RosA and the positive drug azithromycin (positive control); immunofluorescence showed that endometrial CD8 and LC3 increased after CT infection and decreased after RosA and positive drug treatment; the results of transmission electron microscopy showed that RosA and the positive drug azithromycin inhibited the accumulation of autophagosomes; western bolt experiments confirmed the activation of autophagy proteins LC3Ⅱ/Ⅰ, ATG5, Beclin-1, and p62 after CT infection, as well as the inhibition of Ras/Raf/MEK/ERK signaling. RosA and azithromycin inhibition of autophagy proteins activates Ras/Raf/MEK/ERK signaling. In addition, the MEK inhibitor cobimetinib attenuated RosA's protective effect on endometrium by further activating CD8+ T cells on a CT-induced basis, while transmission electron microscopy, immunofluorescence, and western blots showed that cobimetinib blocked ERK signals activation and further induced phagocytosis on a CT-induced basis. These data indicated that RosA can activate the Ras/Raf/MEK/ERK signaling pathway to inhibit autophagy, and RosA could also regulate the activation of immune cells-CD8+T cells to protect the reproductive tract of CT-infected mice.


Assuntos
Autofagia , Linfócitos T CD8-Positivos , Infecções por Chlamydia , Chlamydia trachomatis , Cinamatos , Depsídeos , Sistema de Sinalização das MAP Quinases , Ácido Rosmarínico , Animais , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Feminino , Infecções por Chlamydia/imunologia , Infecções por Chlamydia/tratamento farmacológico , Chlamydia trachomatis/efeitos dos fármacos , Chlamydia trachomatis/imunologia , Camundongos , Depsídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Cinamatos/farmacologia , Proteínas ras/metabolismo , Quinases raf/metabolismo , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL
3.
Neurosci Biobehav Rev ; 162: 105695, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38710424

RESUMO

Predicting repetitive transcranial magnetic stimulation (rTMS) treatment outcomes in major depressive disorder (MDD) could reduce the financial and psychological risks of treatment failure. We systematically reviewed and meta-analyzed studies that leveraged neurophysiological and neuroimaging markers to predict rTMS response in MDD. Five databases were searched from inception to May 25, 2023. The primary meta-analytic outcome was predictive accuracy pooled from classification models. Regression models were summarized qualitatively. A promising marker was identified if it showed a sensitivity and specificity of 80% or higher in at least two independent studies. Searching yielded 36 studies. Twenty-two classification modeling studies produced an estimated area under the summary receiver operating characteristic curve of 0.87 (95% CI = 0.83-0.92), with 86.8% sensitivity (95% CI = 80.6-91.2%) and 81.9% specificity (95% CI = 76.1-86.4%). Frontal theta cordance measured by electroencephalography is closest to proof of concept. Predicting rTMS response using neurophysiological and neuroimaging markers is promising for clinical decision-making. However, replications by different research groups are needed to establish rigorous markers.


Assuntos
Transtorno Depressivo Maior , Neuroimagem , Estimulação Magnética Transcraniana , Humanos , Transtorno Depressivo Maior/terapia , Transtorno Depressivo Maior/diagnóstico por imagem , Transtorno Depressivo Maior/fisiopatologia , Eletroencefalografia , Resultado do Tratamento
4.
Lasers Med Sci ; 39(1): 89, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38453744

RESUMO

Various treatment modalities have been applied to atrophic scars. Fractional CO2 laser treatment has attracted increasingly more attention because of its quicker recovery time and fewer side effects. However, its limitation of sculpting the edge is an urgent shortcoming. In order to achieve a more effective result with fewer complications, we have integrated ultrapulse CO2 and fractional CO2 lasers to for the treatment of facial atrophic scars. The study included 25 patients (10 males and 15 females) diagnosed with moderate to severe atrophic scars between August 2020 and July 2022. All subjects underwent the same surgical treatment. The effects were assessed at baseline, 1 week, 1 month, and 3 months using photographic evidence. Objective evaluation of the results was conducted using a quartile grading scale, while the subjects' satisfaction and any adverse events were also recorded. The patients in the study underwent more than two laser sessions (2-5), resulting in substantial improvement in their appearance. The time interval between each session was 3-6 months. The majority of the patients (19/25, 76%) had a significant or even excellent improvement. Any adverse events observed, such as erythema, superficial crusting, and PIH, were of a mild nature and temporary in duration. This treatment combined two CO2 lasers is an effective and safe choice for atrophic scars in Asians.


Assuntos
Acne Vulgar , Lasers de Gás , Masculino , Feminino , Humanos , Cicatriz/patologia , Dióxido de Carbono , Resultado do Tratamento , Acne Vulgar/complicações , Eritema/etiologia , Lasers de Gás/uso terapêutico , Atrofia/complicações
5.
Dalton Trans ; 53(11): 5133-5146, 2024 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-38380458

RESUMO

The adjustment of crystal symmetry and intramolecular magnetic coupling is of great importance for the construction of high-performance single-molecule magnets. By using an aggregation-induced-emission-active pyridine-carbohydrazone-based Schiff base ligand and phosphine oxides, four dinuclear and one one-dimensional DyIII-based complexes, [Dy2(TPE-pc)2(Bu3PO)2Cl2]·2CH3CN·2H2O (1), [Dy2(TPE-pc)2(Cy3PO)2Cl2] (2), [Dy2(TPE-pc)2(MePA)2Cl2]·2CH3OH (3), [Dy2(TPE-pc)2(Ph3PO)2Cl2]2 (4) and [Dy2(TPE-pc)2(DPPO)Cl2]n (5) (H2TPE-pc = (E)-N'-(2-hydroxy-5-(1,2,2-triphenylvinyl)benzylidene)picolinohydrazide, MePA = N-phenyl-N',N''-bis(morpholinyl) phosphoric triamide, DPPO = piperazine-1,4-diylbis(diphenyl phosphine oxide)), were isolated. All complexes are made up of an enol oxygen-bridged Dy2 unit, where DyIII ions possess a pentagonal bipyramidal geometry with pseudo D5h symmetry. Magnetic measurements reveal that intramolecular DyIII-DyIII couplings are ferromagnetic and all complexes display a significant slow magnetic relaxation phenomenon below 30 K under a zero dc field. Ab initio calculations indicate that the anisotropic magnetic axes of all DyIII ions are approximately perpendicular to the higher-order symmetric axes in all complexes, and that DyIII-DyIII magnetic couplings along the magnetic axes effectively suppress the ground state quantum tunneling effect of magnetization and promote the occurrence of slow magnetic relaxation. Raman relaxation prevails in all complexes. In addition, the H2TPE-pc ligand shows an aggregation-induced emission (AIE) effect; however, all complexes exhibit an aggregation-caused quenching (ACQ) phenomenon.

6.
Nat Struct Mol Biol ; 31(2): 232-245, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38177673

RESUMO

Autophagy is a lysosome-dependent degradation pathway essential for cellular homeostasis, which decreases with age. However, it is unclear how aging induces autophagy decline. Here we show the role of protein S-palmitoylation in autophagy. We identify the palmitoyl acyltransferase DHHC5 as a regulator of autophagy by mediating the palmitoylation of beclin 1, which in turn promotes the formation of ATG14L-containing class III phosphatidylinositol-3-kinase complex I and its lipid kinase activity by promoting the hydrophobic interactions between beclin 1 and adapter proteins ATG14L and VPS15. In aging brains of human and nonhuman primate, the levels of DHHC5 exhibit a marked decrease in expression. We show that DHHC5 deficiency in neurons leads to reduced cellular protein homeostasis in two established murine models of Alzheimer's disease, which exaggerates neurodegeneration in an autophagy-dependent manner. These findings identify reduction of DHHC5-mediated beclin 1 S-palmitoylation as an underlying mechanism by which aging induces autophagy decline.


Assuntos
Aciltransferases , Proteínas Reguladoras de Apoptose , Autofagia , Proteína Beclina-1 , Lipoilação , Animais , Humanos , Camundongos , Aciltransferases/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Proteínas de Membrana/metabolismo , Fosforilação
7.
Indian J Ophthalmol ; 72(Suppl 2): S162-S166, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38271412

RESUMO

The purpose of this study is to examine the viability, precision, and consistency of a computer-based optokinetic nystagmus analyzer (nystagmus meter) for diagnosing eyesight in preschoolers. A total of 59 subjects who could pass the log of minimum angle of resolution (LogMAR) visual acuity chart were divided into three groups by age, 4-, 5-, and 6-year-old groups, and their visual acuity was tested with nystagmus meter. The percentage of children in each age group that could be detected by nystagmus was recorded along with the differences between these groups. The correlation between the test results from the two methods was found for each age group using the correlation coefficient method. Repeated measurements were used to assess the two visual acuity values of the measured nystagmus, and the repeatability of the two measurement techniques for different age groups was compared. The overall measurability of the visual acuity detected by nystagmus was 93.22%, and the measurability of the 4-, 5-, and 6-year-old groups was 90%, 95%, and 94.74%, respectively. There was no statistically significant difference in the measurability of subjects among all age groups (P = 1.0). The outcomes of the LogMAR visual acuity chart had a negative correlation with the visual acuity measured by the nystagmus meter. The overall correlation coefficient R value was -0.80, and the correlation coefficient R value of the 4-, 5-, and 6-year-old groups was -0.79, -0.76, and -0.87, respectively. The nystagmus meter has good feasibility, accuracy, and stability in visual acuity testing and can be used for visual acuity testing in children.


Assuntos
Nistagmo Optocinético , Nistagmo Patológico , Humanos , Pré-Escolar , Nistagmo Patológico/diagnóstico , Acuidade Visual , Testes Visuais , Computadores
8.
Proc Natl Acad Sci U S A ; 121(6): e2320383121, 2024 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-38289948

RESUMO

Rett syndrome (RTT) is a devastating neurodevelopmental disorder primarily caused by mutations in the methyl-CpG binding protein 2 (Mecp2) gene. Here, we found that inhibition of Receptor-Interacting Serine/Threonine-Protein Kinase 1 (RIPK1) kinase ameliorated progression of motor dysfunction after onset and prolonged the survival of Mecp2-null mice. Microglia were activated early in myeloid Mecp2-deficient mice, which was inhibited upon inactivation of RIPK1 kinase. RIPK1 inhibition in Mecp2-deficient microglia reduced oxidative stress, cytokines production and induction of SLC7A11, SLC38A1, and GLS, which mediate the release of glutamate. Mecp2-deficient microglia release high levels of glutamate to impair glutamate-mediated excitatory neurotransmission and promote increased levels of GluA1 and GluA2/3 proteins in vivo, which was reduced upon RIPK1 inhibition. Thus, activation of RIPK1 kinase in Mecp2-deficient microglia may be involved both in the onset and progression of RTT.


Assuntos
Síndrome de Rett , Animais , Camundongos , Ácido Glutâmico/metabolismo , Inflamação/genética , Inflamação/metabolismo , Proteína 2 de Ligação a Metil-CpG/metabolismo , Camundongos Knockout , Microglia/metabolismo , Síndrome de Rett/metabolismo
9.
Journal of Practical Radiology ; (12): 257-260, 2024.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1020196

RESUMO

Objective To investigate the correlation between preoperative MR imaging features and the incidence of tumor metastasis in clear cell renal cell carcinoma.Methods The clinical and preoperative MR imaging data of 64 patients with clear cell renal cell carcinoma were analyzed retrospectively.According to the occurrence of metastasis,the patients were divided into non-metastasis group(n=42)and metastasis group(n=22).The clinical and imaging features of the two groups were analyzed with univariate analysis and multivariate logistic regression.Results The results of the univariate analysis showed that among the clinical and preoperative MR imaging data,there was no significant difference between the two groups in gender,tumor location and intra-tumoral cystic changes(P>0.05),but the patient's ages,clinical symptoms,tumor sizes,necrosis,capsule breakthrough,low signal nodules in T2WI,venous thrombosis,TNM stages,and Fuhrman grades were significantly different between two groups(P<0.05).Multivariate logistic regression analysis showed that low signal nodules in T2WI was an independent predictor of metastasis of clear cell renal cell carcinoma(P=0.028).Combined with diffusion weighted imaging(DWI)sequence,the average apparent diffusion coefficient(ADC)in related areas was measured.The ADC value of low signal nodules area was(0.541±0.101)×10-3 mm2/s in the metastasis group,and the ADC value of non-low signal nodules area was(0.972±0.113)×10-3 mm2/s(P<0.001).Conclusion The metastasis of clear cell renal cell carcinoma is often accompanied by low signal nodules in T2WI in tumors.Combined with the lower ADC value,they can be used as the characteristic imaging features to effectively evaluate the risk of metastasis of clear cell renal cell carcinoma.

10.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-1007285

RESUMO

ObjectiveTo investigate the association between estimated glucose disposal rate (eGDR) and the severity of coronary heart disease. MethodsWe conducted a hospital-based cross-sectional study that included 1258 patients (mean age: 62(53-68) years) who underwent coronary angiography for suspected coronary artery disease (53.9% were male). Insulin resistance level (IR) was calculated according to eGDR formula: eGDR = 21.158 - (0.09 × WC) - (3.407 × hypertension) - (0.551 × HbA1c) [hypertension (yes = 1 / no = 0), HbA1c = HbA1c (%)]. Subjects were grouped according to the eGDR quantile. CAD severity was determined by the number of narrowed vessels: no-obstructive CAD group (all coronary stenosis were<50%, n=704), Single-vessel CAD group (only one involved major coronary artery stenosis≥50%, n=205), Multi-vessel CAD group (two or more involved major coronary arteries stenosis≥50%, n=349); Multivariate logistic regression model was used to analyze the association between eGDR and CAD severity. The linear relationship between eGDR and CAD in the whole range of eGDR was analyzed using restricted cubic spline. Subgroup analyses were used to assess the association between eGDR and CAD severity in different diabetic states. Receiver operating characteristic (ROC) curve analysis were used to evaluate the value of eGDR in improving CAD recognition. ResultsA decrease in the eGDR index was significantly associated with an increased risk of CAD severity (OR: 2.79; 95%CI: 1.72~4.55; P<0.001). In multivariate logistic regression models, individuals with the lowest quantile of eGDR (T1) were 2.79 times more likely to develop multi-vessel CAD than those with the highest quantile of eGDR (T3) (OR: 2.79; 95%CI: 1.72~4.55; P<0.001). Multivariate restricted cubic spline analysis showed that eGDR was negatively associated with CAD and multi-vessel CAD (P-nonlinear>0.05). In non-diabetic patients, compared with the reference group (T3), the T1 group had a significantly increased risk of CAD (OR: 1.42; 95% CI: 1.00~2.01; P<0.05) and multi-vessel CAD (OR: 1.86; 95%CI: 1.21~2.86; P<0.05). No statistical association was found between eGDR and CAD in diabetic patients. In ROC curve analysis, when eGDR was added to traditional model for CAD, significant improvements were observed in the model's recognition of CAD and multi-vessel CAD. ConclusionOur study shows eGDR levels are inversely associated with CAD and CAD severity. eGDR, as a non-insulin measure to assess IR, could be a valuable indicator of CAD severity for population.

11.
Huan Jing Ke Xue ; 44(9): 4809-4818, 2023 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-37699800

RESUMO

Based on OMI remote sensing satellite data, the temporal and spatial characteristics of tropospheric ozone (O3), nitrogen dioxide (NO2), and formaldehyde (HCHO) concentrations in East China from 2005 to 2021 were analyzed, and the backward trajectory (HYSPLIT) model was used to explore their sources. The results showed that ① during the 17 years, the tropospheric O3 concentration steadily increased, reached the maximum value in 2010, and then showed a fluctuating and undulating state. NO2 showed an increasing trend from 2005 to 2012 and slowly decreased from 2012 to 2021. The average HCHO concentration showed an increasing trend from 1.15×1016molec·cm-2 in 2005 to 1.8×1016 molec·cm-2 in 2021. ② In terms of spatial characteristics, the concentrations of the three pollutants generally showed a pattern of high concentration in the north and low concentration in the south, with a high concentration in the north, uncharacteristic concentration in the middle, and low concentration in the south. ③ The sensitivity of O3 was as follows:η<2.3 in spring, which belonged to the VOCs control area; η<4.2 in summer, showing that most areas were NOx-VOCs coordinated control areas and a few areas were VOCs control areas; η<4.2 in autumn, which was primarily controlled by VOCs, with a few of them being NOx-VOC synergistic control areas; and η<2.3 in winter, which was a VOCs-controlled area. VOCs were primarily controlled in Shandong Province. ④ Owing to the high concentration of O3 in Shandong Province from 2005 to 2021, Jinan, the capital city of Shandong Province in 2021, was selected for ozone source analysis. The O3 concentration increased in Jinan in 2021 owing to two aspects. First, the long-distance air transportation primarily originated from Lianyungang City in Jiangsu Province and Cangzhou City in Hebei Province. Second, the close air mass transport originated from the pollution of cities near Jinan and the economic zones of the Yellow Sea and Bohai Sea, and the aggregation analysis results corresponded with those of the potential source contribution factor algorithm (PSCF) and the weighted trajectory analysis (CWT).

12.
ACS Appl Mater Interfaces ; 15(32): 38693-38706, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37542464

RESUMO

Inspired by life's interaction networks, ongoing efforts are to increase complexity and responsiveness of multicomponent interactions in the system for sensing, programmable control, or information processing. Although exquisite preparation of single uniform-morphology nanomaterials has been extremely explored, the potential value of facile and one-pot preparation of multimorphology nanomaterials has been seriously ignored. Here, multimorphological silver nanomaterials (M-AgN) prepared by one pot can form interaction networks with various analytes, which can be successfully realized from multimode and multianalyte colorimetric sensing to molecular information technology (logic computing and security). The interaction of M-AgN with multianalytes not only induces multisignal responses (including color, absorbance, and wavelength shift) for sensing metal ions (Cr3+, Hg2+, and Ni2+) but also can controllably reshape its four morphologies (nanodots, nanoparticles, nanorods, and nanotriangles). By abstracting binary relationships between analytes and response signals, multicoding parallel logic operations (including simple logic gates and cascaded circuits) can be performed. In addition, taking advantage of natural concealment and molecular response characteristics of M-AgN nanosystems can also realize molecular information encoding, encryption, and hiding. This research not only promotes the construction and application of multinano interaction systems based on multimorphology and multicomponent nanoset but also provides a new imagination for the integration of sensing, logic, and informatization.

13.
Adv Sci (Weinh) ; 10(27): e2300470, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37505480

RESUMO

Myocardial infarction (MI) causes excessive damage to the myocardium, including the epicardium. However, whether pluripotent stem cell-derived epicardial cells (EPs) can be a therapeutic approach for infarcted hearts remains unclear. Here, the authors report that intramyocardial injection of human embryonic stem cell-derived EPs (hEPs) at the acute phase of MI ameliorates functional worsening and scar formation in mouse hearts, concomitantly with enhanced cardiomyocyte survival, angiogenesis, and lymphangiogenesis. Mechanistically, hEPs suppress MI-induced infiltration and cytokine-release of inflammatory cells and promote reparative macrophage polarization. These effects are blocked by a type I interferon (IFN-I) receptor agonist RO8191. Moreover, intelectin 1 (ITLN1), abundantly secreted by hEPs, interacts with IFN-ß and mimics the effects of hEP-conditioned medium in suppression of IFN-ß-stimulated responses in macrophages and promotion of reparative macrophage polarization, whereas ITLN1 downregulation in hEPs cancels beneficial effects of hEPs in anti-inflammation, IFN-I response inhibition, and cardiac repair. Further, similar beneficial effects of hEPs are observed in a clinically relevant porcine model of reperfused MI, with no increases in the risk of hepatic, renal, and cardiac toxicity. Collectively, this study reveals hEPs as an inflammatory modulator in promoting infarct healing via a paracrine mechanism and provides a new therapeutic approach for infarcted hearts.


Assuntos
Células-Tronco Embrionárias Humanas , Infarto do Miocárdio , Suínos , Camundongos , Humanos , Animais , Miocárdio , Miócitos Cardíacos , Infarto do Miocárdio/tratamento farmacológico , Macrófagos
14.
Life Sci ; 329: 121936, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37453576

RESUMO

Retinoid X receptor (RXR), particularly RXRα, has been implicated in cardiovascular diseases. However, the functional role of RXR activation in myocardial infarction (MI) remains unclear. This study aimed to determine the effects of RXR agonists on MI and to dissect the underlying mechanisms. Sprague-Dawley (SD) rats were subjected to MI and then treated (once daily for 4 weeks) with either RXR agonist bexarotene (10 or 30 mg/kg body weight) or vehicle. Heart function was determined using echocardiography and cardiac hemodynamic measurements. Four weeks post MI, myocardial tissues were collected to evaluate cardiac remodeling. Primary cardiac fibroblasts (CFs) were treated with or without RXR ligand 9-cis-RA followed by stimulation with TGF-ß1. Immunoblot, immunofluorescence, and co-immunoprecipitation were performed to elucidate the regulatory role of RXR agonists in TGF-ß1/Smad signaling. In vivo treatment with Bexarotene moderately affects systemic inflammation and apoptosis and ameliorated left ventricular dysfunction after MI in rat model. In contrast, bexarotene significantly inhibited post-MI myocardial fibrosis. Immunoblot analysis of heart tissue homogenates from MI rats revealed that bexarotene regulated the activation of the TGF-ß1/Smad signaling pathway. In vitro, 9-cis-RA inhibited the TGF-ß1-induced proliferation and collagen production of CFs. Importantly, upon activation by 9-cis-RA, RXRα interacted with p-Smad2 in cytoplasm, inhibiting the TGF-ß1-induced nuclear translocation of p-Smad2, thereby negatively regulating TGF-ß1/Smad signaling and attenuating the fibrotic response of CFs. These findings suggest that RXR agonists ameliorate post-infarction myocardial fibrosis, maladaptive remodeling, and heart dysfunction via attenuation of fibrotic response in CFs through inhibition of the TGF-ß1/Smad pathway activation.


Assuntos
Cardiomiopatias , Infarto do Miocárdio , Ratos , Animais , Ratos Sprague-Dawley , Receptores X de Retinoides , Bexaroteno/farmacologia , Fator de Crescimento Transformador beta1/metabolismo , Remodelação Ventricular , Infarto do Miocárdio/metabolismo , Cardiomiopatias/patologia , Fibroblastos/metabolismo , Fibrose , Miocárdio/metabolismo
15.
Front Endocrinol (Lausanne) ; 14: 1150547, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37484967

RESUMO

Objectives: The aim is to evaluate the effect of a novel 14-day fasting regimen on the balance between skeletal muscle and adipose tissue composition which might associate with inflammatory factors. Our analysis includes basic physical examinations, clinical laboratory analysis, bioelectrical impedance and biochemical analytic assessments of healthy volunteers. Methods: Eight healthy subjects were randomly selected from a pool of volunteers to undergo a continual dietary deprivation (CDD) regimen. Individuals were assigned to take Flexible Abrosia (FA, prebiotic combination) plus appropriate mineral supplement of potassium and magnesium at 3 mealtime every day to prevent potential injury from starved intestinal flora and avoid spasms of smooth muscle due to hunger. Physical and medical examinations were conducted and blood samples were collected at following timepoints: before CDD as self-control (0D), day 7 and day 14 during fasting, and 7-21days and/or 2~3mo after refeeding. Results: The combination of FA and mineral supplements significantly decreased self-reported physical response of starvation, with tolerable hunger-mediated sensations experienced during CDD. Bioelectrical and biochemical results indicated significant reduction in both muscle lean and fat mass on day 7. Meanwhile, markers related to fat composition consistently decreased during and after CDD. In addition, most biochemical marker levels, including serum proteins, reached their inflection points at the 7th day of CDD as compared to the control measurements. Levels of these factors started to show a relative plateau, or reversed direction upon the 14th day of CDD. The exceptions of above factors were myostatin and complement protein C3, which remained at lower concentrations in the blood throughout CDD, and were unable to fully recover toward baseline levels even after 3 months' refeeding. Conclusion: Our results indicated that human subjects undergoing prolonged dietary restriction were well protected by FA and mineral ions from gut injury or physical discomfort of starvation. Most factors showed a relative plateau response at the end of 14D-CDD. The muscle tissues were well preserved during prolonged fasting, and an improved protein/lipid ratio was observed. Upon refeeding, constant lower levels of myostatin and complement C3 were maintained after CDD implies a long-term beneficial effect in dealing with anti-aging and inflammation.


Assuntos
Miostatina , Inanição , Humanos , Complemento C3 , Regulação para Baixo , Jejum , Dieta
16.
Small ; 19(29): e2207436, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37026417

RESUMO

Bimetallic nanomaterials (BNMs) have been used in sensing, biomedicine, and environmental remediation, but their multipurpose and comprehensive applications in molecular logic computing and information security protection have received little attention. Herein, This synthesis method is achieved by sequentially adding reactants under ice bath conditions. Interestingly, Ag-Cr NPs can dynamically selectively sense anions and reductants in multiple channels. Especially, ClO- can be quantitatively detected by oxidizing Ag-Cr NPs with detection limits of 98.37 nM (at 270 nm) and 31.83 nM (at 394 nm). Based on sequential-dependent synthesis process of Ag-Cr NPs, Boolean logic gates and customizable molecular keypad locks are constructed by setting the reactants as the inputs, the states of the resulting solutions as the outputs. Furthermore, dynamically selective response patterns of the Ag-Cr NPs can be converted into binary strings to exploit molecular crypto-steganography to encode, store, and hide information. By integrating the three dimensions of authorization, encryption, and steganography, 3 in 1 advanced information protection based on Ag-Cr nanosensing system can be achieved, which can enhance the anti-cracking ability of information. This research will promote the development and application of nanocomposites in the field of information security and deepen the connection between molecular sensing and the information world.

17.
Am J Transl Res ; 15(2): 1204-1214, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36915740

RESUMO

OBJECTIVES: Scarring is a common but intricate problem, and topical anti-scarring drugs are the most widely used treatment. However, the wide range of drugs available makes it difficult for doctors and patients to choose from because of the lack of clinical comparisons. Therefore, we conducted an observational study to compare the clinical efficacy of different topical anti-scarring drugs. METHODS: Patients with post-suturing facial scars were enrolled in this study. The questionnaire was designed to record the basic characteristics of the patients. The Vancouver Scar Scale, SCAR scale, and measurements of scar width and thickness were used to evaluate scar quality. Patients who met the inclusion criteria were divided into four groups for comparison: the silicone preparation (SP), onion extract (OE), asiaticoside (AC) groups, and the untreated blank control (BC) group. The overall data were analyzed before they were confined to the zygomatic region. RESULTS: A total of 127 eligible patients were enrolled in this study. The results of the total and zygomatic scars demonstrated that SP, OE, and AC groups resulted in narrower scars and lower scar scale scores. The SP group depicted higher melanin efficacy than the other two groups. The OE group had the best pliability, whereas the AC group had the thinnest scar. CONCLUSIONS: In this study, we acquired expertise with different topical anti-scar agents: SP significantly reduced melanin levels, OE mainly benefited scar pliability, and AC was better at reducing scar thickness. These differences may be more instructive for clinical applications.

18.
Pharmaceutics ; 15(2)2023 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-36840021

RESUMO

The global increase and prevalence of inflammatory-mediated diseases have been a great menace to human welfare. Several works have demonstrated the anti-inflammatory potentials of natural polyphenolic compounds, including flavonoid derivatives (EGCG, rutin, apigenin, naringenin) and phenolic acids (GA, CA, etc.), among others (resveratrol, curcumin, etc.). In order to improve the stability and bioavailability of these natural polyphenolic compounds, their recent loading applications in both organic (liposomes, micelles, dendrimers, etc.) and inorganic (mesoporous silica, heavy metals, etc.) nanocarrier technologies are being employed. A great number of studies have highlighted that, apart from improving their stability and bioavailability, nanocarrier systems also enhance their target delivery, while reducing drug toxicity and adverse effects. This review article, therefore, covers the recent advances in the drug delivery of anti-inflammatory agents loaded with natural polyphenolics by the application of both organic and inorganic nanocarriers. Even though nanocarrier technology offers a variety of possible anti-inflammatory advantages to naturally occurring polyphenols, the complexes' inherent properties and mechanisms of action have not yet been fully investigated. Thus, expanding the quest on novel natural polyphenolic-loaded delivery systems, together with the optimization of complexes' activity toward inflammation, will be a new direction of future efforts.

19.
Prog Neurobiol ; 222: 102404, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36642095

RESUMO

AMPAR-lacking silent synapses are prevailed and essential for synaptic refinement and synaptic plasticity in developing brains. In mature brain, they are sparse but could be induced under several pathological conditions. How they are regulated molecularly is far from clear. miR-34a is a highly conserved and brain-enriched microRNA with age-dependent upregulated expression profile. Its neuronal function in mature brain remains to be revealed. Here by analyzing synaptic properties of the heterozygous miR-34a knock out mice (34a_ht), we have discovered that mature but not juvenile 34a_ht mice have more silent synapses in the hippocampus accompanied with enhanced synaptic NMDAR but not AMPAR function and increased spine density. As a result, 34a_ht mice display enhanced long-term potentiation (LTP) in the Schaffer collateral synapses and better spatial learning and memory. We further found that Creb1 is a direct target of miR-34a, whose upregulation and activation may mediate the silent synapse increment in 34a_ht mice. Hence, we reveal a novel physiological role of miR-34a in mature brains and provide a molecular mechanism underlying silent synapse regulation.


Assuntos
MicroRNAs , Plasticidade Neuronal , Camundongos , Animais , Plasticidade Neuronal/fisiologia , Potenciação de Longa Duração/fisiologia , Hipocampo/metabolismo , Sinapses/metabolismo , MicroRNAs/metabolismo , Camundongos Knockout
20.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-970505

RESUMO

By various chromatographic techniques and extensive spectroscopic methods, 17 abietane diterpenoids were isolated from the dichloromethane fraction of the 95% ethanol cold-soak extracts of the seeds of Pseudolarix amabilis, namely pseudoamaol A(1), 12α-hydroxyabietic acid(2), 12-methoxy-7,13-abietadien-18-oic acid(3), 13-hydroxy-8,11,13-podocarpatrien-18-oic acid(4), 15-hydroxy-7,13-abietadien-12-on-18-oic acid(5), 8(14)-podocarpen-13-on-18-oic acid(6), holophyllin K(7), metaglyptin B(8), 7α-hydroxydehydroabietinsaure-methylester(9), 7-oxodehydroabietic acid(10), 15-hydroxy-7-oxodehydroabietinsaure-methy-lester(11), 15-methoxydidehydroabietic acid(12), 7-oxo-15-hydroxy-dehydroabietic acid(13), 15-hydroxydehydroabietic acid(14), 8,11,13-abietatriene-15,18-diol(15), 8,11,13-abietatriene-15-hydroxy-18-succinic acid(16), and 7β-hydroxydehydroabie-tic acid(17). Compound 1 was a new compound. The isolated compounds were evaluated for their antitumor activities(HepG2, SH-SY5Y, K562), and compounds 8 and 17 showed potential cytotoxic activity against K562 cells, with IC_(50) values of 26.77 and 37.35 μmol·L~(-1), respectively.


Assuntos
Humanos , Estrutura Molecular , Neuroblastoma , Diterpenos/química , Antineoplásicos
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