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1.
PeerJ ; 12: e17623, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38952974

RESUMO

Although exercise training has been shown to enhance neurological function, there is a shortage of research on how exercise training affects the temporal-spatial synchronization properties of functional networks, which are crucial to the neurological system. This study recruited 23 professional and 24 amateur dragon boat racers to perform simulated paddling on ergometers while recording EEG. The spatiotemporal dynamics of the brain were analyzed using microstates and omega complexity. Temporal dynamics results showed that microstate D, which is associated with attentional networks, appeared significantly altered, with significantly higher duration, occurrence, and coverage in the professional group than in the amateur group. The transition probabilities of microstate D exhibited a similar pattern. The spatial dynamics results showed the professional group had lower brain complexity than the amateur group, with a significant decrease in omega complexity in the α (8-12 Hz) and ß (13-30 Hz) bands. Dragon boat training may strengthen the attentive network and reduce the complexity of the brain. This study provides evidence that dragon boat exercise improves the efficiency of the cerebral functional networks on a spatiotemporal scale.


Assuntos
Encéfalo , Eletroencefalografia , Humanos , Masculino , Eletroencefalografia/métodos , Encéfalo/fisiologia , Adulto , Adulto Jovem , Exercício Físico/fisiologia , Esportes Aquáticos/fisiologia , Atenção/fisiologia , Feminino
2.
PLoS One ; 19(7): e0306048, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38968326

RESUMO

BACKGROUND: The linkage between psoriasis and hypertension has been established through observational studies. Despite this, a comprehensive assessment of the combined effects of psoriasis and hypertension on all-cause mortality is lacking. The principal aim of the present study is to elucidate the synergistic impact of psoriasis and hypertension on mortality within a representative cohort of adults residing in the United States. METHODS: The analysis was conducted on comprehensive datasets derived from the National Health and Nutrition Examination Study spanning two distinct periods: 2003-2006 and 2009-2014. The determination of psoriasis status relied on self-reported questionnaire data, whereas hypertension was characterized by parameters including systolic blood pressure ≥ 140 mmHg, diastolic blood pressure ≥ 90 mmHg, self-reported physician diagnosis, or the use of antihypertensive medication. The assessment of the interplay between psoriasis and hypertension employed multivariable logistic regression analyses. Continuous monitoring of participants' vital status was conducted until December 31, 2019. A four-level variable amalgamating information on psoriasis and hypertension was established, and the evaluation of survival probability utilized the Kaplan-Meier curve alongside Cox regression analysis. Hazard ratios (HRs) and their associated 95% confidence intervals (CIs) were computed to scrutinize the correlation between psoriasis/hypertension and all-cause mortality. RESULTS: In total, this study included 19,799 participants, among whom 554 had psoriasis and 7,692 had hypertension. The findings from the logistic regression analyses indicated a heightened risk of hypertension among individuals with psoriasis in comparison to those devoid of psoriasis. Throughout a median follow-up spanning 105 months, 1,845 participants experienced all-cause death. In comparison to individuals devoid of both hypertension and psoriasis, those with psoriasis alone exhibited an all-cause mortality HR of 0.73 (95% CI: 0.35-1.53), individuals with hypertension alone showed an HR of 1.78 (95% CI: 1.55-2.04), and those with both psoriasis and hypertension had an HR of 2.33 (95% CI: 1.60-3.40). In the course of a stratified analysis differentiating between the presence and absence of psoriasis, it was noted that hypertension correlated with an elevated risk of all-cause mortality in individuals lacking psoriasis (HR 1.77, 95% CI: 1.54-2.04). Notably, this association was further accentuated among individuals with psoriasis, revealing an increased HR of 3.23 (95% CI: 1.47-7.13). CONCLUSIONS: The outcomes of our investigation demonstrated a noteworthy and positive association between psoriasis, hypertension, and all-cause mortality. These findings indicate that individuals who have both psoriasis and hypertension face an increased likelihood of mortality.


Assuntos
Hipertensão , Psoríase , Humanos , Psoríase/complicações , Psoríase/mortalidade , Masculino , Hipertensão/complicações , Hipertensão/mortalidade , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto , Idoso , Fatores de Risco , Estados Unidos/epidemiologia , Modelos de Riscos Proporcionais , Inquéritos Nutricionais
3.
Artigo em Inglês | MEDLINE | ID: mdl-38832362

RESUMO

OBJECTIVE: This study aimed to develop and validate a prenatal nomogram to predict the risk of placenta accreta spectrum (PAS) in women with one previous cesarean delivery. METHODS: This retrospective study enrolled 5157 pregnant women with one previous cesarean delivery in China from January 2021 to January 2023. The nomogram was developed from a training cohort of 3612 pregnant women and tested on a validation cohort of 1545 pregnant women. Multivariate regression analysis was performed using the minimum value of the Akaike information criterion to select prognostic factors that can be included in the nomogram. We evaluated the nomogram by the area under the receiver operating characteristic (ROC) curve, calibration curves, and the decision curve analysis (DCA). RESULTS: PAS occurred in 199 (5.51%) and 80 (5.18%) patients in the training and validation cohorts, respectively. Backward stepwise algorithms in the multivariable logistic regression model determined abortion, hypertensive disorders complicating pregnancy, fetal position, and placenta previa as relevant PAS predictors. The area under the ROC curve for the nomogram was 0.770 (95% confidence interval [CI] 0.733-0.807) and 0.791 (95% CI 0.730-0.853) for the training and validation cohorts, respectively. The calibration curves indicated that the nomogram's prediction probability was consistent with the actual probability. The DCA curve revealed that the nomogram has potential clinical benefit. CONCLUSION: A prenatal nomogram was developed for PAS in our study, which helped obstetricians determine potential patients with PAS and make sufficient preoperative preparation to reduce maternal and neonatal complications.

4.
Light Sci Appl ; 13(1): 138, 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38866757

RESUMO

Light-emitting diodes (LEDs) based on perovskite semiconductor materials with tunable emission wavelength in visible light range as well as narrow linewidth are potential competitors among current light-emitting display technologies, but still suffer from severe instability driven by electric field. Here, we develop a stable, efficient and high-color purity hybrid LED with a tandem structure by combining the perovskite LED and the commercial organic LED technologies to accelerate the practical application of perovskites. Perovskite LED and organic LED with close photoluminescence peak are selected to maximize photon emission without photon reabsorption and to achieve the narrowed emission spectra. By designing an efficient interconnecting layer with p-type interface doping that provides good opto-electric coupling and reduces Joule heating, the resulting green emitting hybrid LED shows a narrow linewidth of around 30 nm, a peak luminance of over 176,000 cd m-2, a maximum external quantum efficiency of over 40%, and an operational half-lifetime of over 42,000 h.

5.
Arch Dermatol Res ; 316(6): 214, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787420

RESUMO

We aimed to unveil the underlying pathogenic mechanisms of skin cancer in relation to metabolic factors and pathway mechanisms. This study utilized the TwoSample Mendelian randomization (MR) method to investigate the causal relationship between 1400 plasma metabolites and skin cancer. The primary method employed was the inverse variance weighting (IVW). Through IVW analysis, we found 105 plasma metabolites associated with Basal Cell Carcinoma (BCC), with the highest association observed for Prolylglycine levels (OR [95% CI]: 1.1902 [1.0274, 1.3788]). For Malignant Melanoma of Skin (MSS), 68 plasma metabolites were linked, with the highest causal relationship seen for 3-Hydroxybutyrate levels (OR [95% CI]: 1.0030 [1.0013, 1.0048]). Regarding actinic keratosis (AK), and the highest association observed for Hexadecadienoate (16:2n6) levels (OR [95% CI]: 1.3302 [1.0333, 1.7125]). Glycerol to palmitoylcarnitine (16: n6) levels (OR [95% CI]: 1.3302 [1.0333, 1.125]) were found to be significant for BCC and AK. Palmitoylcarnitine (C16) had the most positive causal effect for BCC (OR [95% CI]: 1.1777 [1.0493, 1.3218]), while 5-hydroxy-2-methylpyridine sulfate levels had the highest effect for AK (OR [95% CI]: 1.1788 [1.0295, 1.3498]). And 4-guanidinobutanoate levels had the largest positive causal effect (OR [95% CI]: 1.0857 [1.0417, 1.1317]) for BCC, and X-11880 levels for MSS (OR [95% CI]: 1.0013 [1.0000, 1.0025]). The study revealed a positive association between hereditary Glycerol to palmitoylcarnitine (C16) and 5-hydroxy-2-methylpyridine sulfate levels with the risk of developing BCC and AK. Additionally, 4-guanidinobutanoate levels and X 11880 levels were found to be positively associated with the risk of BCC and MMS.


Assuntos
Carcinoma Basocelular , Análise da Randomização Mendeliana , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/epidemiologia , Carcinoma Basocelular/sangue , Carcinoma Basocelular/genética , Carcinoma Basocelular/epidemiologia , Melanoma/sangue , Melanoma/genética , Melanoma/epidemiologia , Ceratose Actínica/sangue , Ceratose Actínica/genética , Ácido 3-Hidroxibutírico/sangue , Predisposição Genética para Doença , Melanoma Maligno Cutâneo
6.
Front Cell Infect Microbiol ; 14: 1382145, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38736748

RESUMO

Carbapenem-resistant Acinetobacter baumannii (CRAB) has become a new threat in recent years, owing to its rapidly increasing resistance to antibiotics and new effective therapies are needed to combat this pathogen. Phage therapy is considered to be the most promising alternative for treating CRAB infections. In this study, a novel phage, Ab_WF01, which can lyse clinical CRAB, was isolated and characterized from hospital sewage. The multiplicity of infection, morphology, one-step growth curve, stability, sensitivity, and lytic activity of the phage were also investigated. The genome of phage Ab_WF01 was 41, 317 bp in size with a GC content of 39.12% and encoded 51 open reading frames (ORFs). tRNA, virulence, and antibiotic resistance genes were not detected in the phage genome. Comparative genomic and phylogenetic analyses suggest that phage Ab_WF01 is a novel species of the genus Friunavirus, subfamily Beijerinckvirinae, and family Autographiviridae. The in vivo results showed that phage Ab_WF01 significantly increased the survival rate of CRAB-infected Galleria mellonella (from 0% to 70% at 48 h) and mice (from 0% to 60% for 7 days). Moreover, after day 3 post-infection, phage Ab_WF01 reduced inflammatory response, with strongly ameliorated histological damage and bacterial clearance in infected tissue organs (lungs, liver, and spleen) in mouse CRAB infection model. Taken together, these results show that phage Ab_WF01 holds great promise as a potential alternative agent with excellent stability for against CRAB infections.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Bacteriófagos , Carbapenêmicos , Genoma Viral , Terapia por Fagos , Filogenia , Esgotos , Acinetobacter baumannii/virologia , Acinetobacter baumannii/efeitos dos fármacos , Esgotos/virologia , Esgotos/microbiologia , Animais , Carbapenêmicos/farmacologia , Bacteriófagos/genética , Bacteriófagos/fisiologia , Bacteriófagos/classificação , Bacteriófagos/isolamento & purificação , Infecções por Acinetobacter/microbiologia , Camundongos , Antibacterianos/farmacologia , Fases de Leitura Aberta , Modelos Animais de Doenças , Mariposas/virologia , Mariposas/microbiologia , Composição de Bases
7.
Nanoscale ; 16(21): 10441-10447, 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38742531

RESUMO

ZnSeTe quantum dots (QDs) have been employed as promising emitters for blue QD-based light-emitting diodes (QLEDs) due to their unique optoelectronic properties and environmental friendliness. However, such QLEDs usually suffer from serious efficiency roll-off primarily stemming from exciton loss at the interface of the QD layer and the ZnMgO (ZMO) electron transport layer (ETL), which remarkably hinders their application in flat-panel displays. Herein, we propose an in situ hybridization strategy that involves the pre-introduction of amino alcohols into the reaction solution. This strategy effectively suppresses the nucleophilic condensation process by facilitating the coordination of ammonium and hydroxyl groups with metal cations (M2+, i.e. Zn2+ and Mg2+). It slows down the growth rate of ZMO nanoparticles (NPs) while simultaneously facilitating M-O coordination, resulting in the synthesis of small-sized and low-defect ZMO NPs. Notably, this in situ hybridization approach not only alleviates emission quenching at the QDs/ETL interface but also elevates the energy level of the ETL for enhancing carrier injection. We further investigated the impact of amino alcohols with varying carbon-chain lengths on the performance of ZMO NPs and the corresponding LED devices. The optimal blue ZnSeTe QLED demonstrates an impressive EQE of 8.6% with only an ∼11% drop when the current density is increased to 200 mA cm-2, and the device operating lifetime extends to over 1300 h. Conversely, the device utilizing traditionally post-treated ZMO NPs as the ETL exhibits 45% efficiency roll-off and device lifetime of merely 190 h.

8.
J Perinatol ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38802655

RESUMO

OBJECTIVE: This study was to systematically assess the occipital lobe gray and white matter volume of isolated ventriculomegaly (IVM) fetuses with MRI and to follow up the neurodevelopment of participants. METHOD: MRI was used to evaluate 37 IVM fetuses and 37 control fetuses. The volume of gray and white matter in each fetal occipital gyrus was manually segmented and compared, and neurodevelopment was followed up and assessed in infancy and early childhood. RESULT: Compared with the control group, the volume of gray matter in occipital lobe increased in the IVM group, and the incidence of neurodevelopmental delay increased. CONCLUSION: We tested the hypothesis that prenatal diagnosis IVM represents a biological marker for development in fetal occipital lobe. Compared with the control group, the IVM group showed differences in occipital gray matter development and had a higher risk of neurodevelopmental delay.

9.
Adv Sci (Weinh) ; 11(22): e2310162, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38602439

RESUMO

The inflammatory response is a key factor affecting tissue regeneration. Inspired by the immunomodulatory role of spermidine, an injectable double network hydrogel functionalized with spermidine (DN-SPD) is developed, where the first and second networks are formed by dynamic imine bonds and non-dynamic photo-crosslinked bonds respectively. The single network hydrogel before photo-crosslinking exhibits excellent injectability and thus can be printed and photo-crosslinked in situ to form double network hydrogels. DN-SPD hydrogel has demonstrated desirable mechanical properties and tissue adhesion. More importantly, an "operando" comparison of hydrogels loaded with spermidine or diethylenetriamine (DETA), a sham molecule resembling spermidine, has shown similar physical properties, but quite different biological functions. Specifically, the outcomes of 3 sets of in vivo animal experiments demonstrate that DN-SPD hydrogel can not only reduce inflammation caused by implanted exogenous biomaterials and reactive oxygen species but also promote the polarization of macrophages toward regenerative M2 phenotype, in comparison with DN-DETA hydrogel. Moreover, the immunoregulation by spermidine can also translate into faster and more natural healing of both acute wounds and diabetic wounds. Hence, the local administration of spermidine affords a simple but elegant approach to attenuate foreign body reactions induced by exogenous biomaterials to treat chronic refractory wounds.


Assuntos
Diabetes Mellitus Experimental , Modelos Animais de Doenças , Hidrogéis , Inflamação , Espermidina , Cicatrização , Espermidina/farmacologia , Animais , Cicatrização/efeitos dos fármacos , Hidrogéis/química , Inflamação/tratamento farmacológico , Camundongos , Masculino , Materiais Biocompatíveis
10.
Nanotechnology ; 35(30)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38604152

RESUMO

The pursuit of van der Waals (vdW) heterostructures with high Curie temperature and strong perpendicular magnetic anisotropy (PMA) is vital to the advancement of next generation spintronic devices. First-principles calculations are used to study the electronic structures and magnetic characteristics of GaN/VS2vdW heterostructure under biaxial strain and electrostatic doping. Our findings show that a ferromagnetic ground state with a remarkable Curie temperature (477 K), much above room temperature, exists in GaN/VS2vdW heterostructure and 100% spin polarization efficiency. Additionally, GaN/VS2vdW heterostructure still maintains PMA under biaxial strain, which is indispensable for high-density information storage. We further explore the electron, magnetic, and transport properties of VS2/GaN/VS2vdW sandwich heterostructure, where the magnetoresistivity can reach as high as 40%. Our research indicates that the heterostructure constructed by combining the ferromagnet VS2and the non-magnetic semiconductor GaN is a promising material for vdW spin valve devices at room temperature.

11.
Artigo em Inglês | MEDLINE | ID: mdl-38439666

RESUMO

Myocardial ischemia/reperfusion (I/R) injury is a classic type of cardiovascular disease characterized by injury to cardiomyocytes leading to different types of cell death. The degree of irreversible myocardial damage is closely related to age, and ferroptosis is involved in cardiomyocyte damage. However, the mechanisms underlying ferroptosis regulation in aging myocardial I/R injury are still unclear. The present study aims to explore the underlying mechanism of piRNA regulation in ferroptosis. Using left anterior descending coronary artery ligation in an aging rat model and a D-galactose-induced rat cardiomyocyte line (H9C2) to construct an aging cardiomyocyte model, we investigate whether ferroptosis occurs after reperfusion injury in vitro and in vivo. This study focuses on the upregulation of piR-000699 after hypoxia/reoxygenation treatment in aging cardiomyocytes by observing hypoxia/reoxygenation (H/R) injury indicators and ferroptosis-related indicators and clarifying the role of piR-000699 in H/R injury caused by ferroptosis in aging cardiomyocytes. Bioinformatics analysis reveals that SLC39A14 is a gene that binds to piR-000699. Our data show that ferroptosis plays an important role in I/R injury both in vivo and in vitro. Furthermore, the results show the potential role of piR-000699 in regulating SLC39A14 in ferroptosis in aging cardiomyocytes under hypoxia/reoxygenation conditions. Together, our results reveal that the mechanism by which piR-000699 binds to SLC39A14 regulates ferroptosis in aging myocardial I/R injury.

12.
Parkinsonism Relat Disord ; 123: 106075, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38492517

RESUMO

INTRODUCTION: Sialorrhea is a common neurological manifestation of Parkinson's disease (PD). No specifically designed prospective study has tested the effects of deep brain stimulation of the subthalamic nucleus (STN-DBS) on sialorrhea in patients with advanced PD. We focused on the effect of STN-DBS on the incidence of sialorrhea in patients with PD. METHODS: This multicenter, prospective, non-randomized concurrent clinical trial analyzed the incidence of sialorrhea during long-term follow-up in 170 patients with advanced PD (84 patients with STN-DBS and 86 patients with medication therapy). RESULTS: After STN-DBS, 58.1% of patients presented with sialorrhea (Drooling Rating Scale (DRS) > 5) compared with 39.3% of patients with medication therapy (P < 0.001). STN-DBS stimulation demonstrated a significant increase in DRS and Drooling Severity and Frequency Scale (DSFS) compared with the patients with medication therapy (P < 0.001). At follow-up, the onabotulinumtoxin-A (BTX-A) injection ratio was significantly higher in the STN-DBS group (29.8% vs. 11.9%, P = 0.0057) compared with the patients with medication therapy. CONCLUSIONS: STN-DBS increased the risk of sialorrhea in patients with advanced PD. TRIAL REGISTRATION: clinicaltrials. gov (NCT06090929).


Assuntos
Estimulação Encefálica Profunda , Doença de Parkinson , Sialorreia , Núcleo Subtalâmico , Humanos , Doença de Parkinson/complicações , Doença de Parkinson/terapia , Sialorreia/etiologia , Sialorreia/terapia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Prospectivos , Toxinas Botulínicas Tipo A/administração & dosagem , Seguimentos
13.
J Biomed Mater Res A ; 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38501727

RESUMO

Chronic inflammation at diabetic wound sites results in the uncontrolled accumulation of pro-inflammatory factors and reactive oxygen species (ROS), which impedes cell proliferation and delays wound healing. To promote the healing of diabetic wounds, chitosan/gelatin hydrogels containing ceria nanoparticles (CNPs) of various sizes were created in the current study. CNPs' efficacy in removing O 2 • - $$ {\mathrm{O}}_2^{\bullet -} $$ , •OH, and H2 O2 was demonstrated, and the scavenging ability of CNPs of varying sizes was compared. The in vitro experiments demonstrated that hydrogels containing CNPs could effectively protect cells from ROS-induced damage and facilitate mouse fibroblast migration. Furthermore, during the treatment of diabetic wounds in vivo, hydrogels containing CNPs exhibited anti-inflammatory activity and could reduce the expression of the pro-inflammatory factors TNF-α (above 30%), IL-6 (above 90%), and IL-1ß (above 80%), and effectively promote wound closure (above 80%) by inducing re-epithelialization, collagen deposition, and angiogenesis. In addition, the biological properties and therapeutic effects of hydrogels containing CNPs of various sizes were compared and discussed. The finding revealed that hydrogels with 4 nm CNPs exhibited more significant biological properties and had implications for diabetic wound treatment.

14.
Int J Mol Sci ; 25(5)2024 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-38474185

RESUMO

Poly(propylene carbonate) (PPC) is an emerging "carbon fixation" polymer that holds the potential to become a "biomaterial of choice" in healthcare owing to its good biocompatibility, tunable biodegradability and safe degradation products. However, the commercialization and wide application of PPC as a biomedical material are still hindered by its narrow processing temperature range, poor mechanical properties and hydrophobic nature. Over recent decades, several physical, chemical and biological modifications of PPC have been achieved by introducing biocompatible polymers, inorganic ions or small molecules, which can endow PPC with better cytocompatibility and desirable biodegradability, and thus enable various applications. Indeed, a variety of PPC-based degradable materials have been used in medical applications including medical masks, surgical gowns, drug carriers, wound dressings, implants and scaffolds. In this review, the molecular structure, catalysts for synthesis, properties and modifications of PPC are discussed. Recent biomedical applications of PPC-based biomaterials are highlighted and summarized.


Assuntos
Materiais Biocompatíveis , Polímeros , Propano/análogos & derivados , Materiais Biocompatíveis/química , Polímeros/química , Próteses e Implantes
15.
Ren Fail ; 46(1): 2325644, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38445391

RESUMO

OBJECTIVE: In China, most of the patients who underwent kidney transplants have unknown causes of end-stage renal disease (uESRD). However, little is known regarding the incidence of graft glomerulonephritis (GN) and graft survival in kidney transplant recipients (KTRs) with uESRD. METHODS: In this retrospective cohort study, 473 of the 565 KTRs who underwent kidney transplantation (KTx) from 2015 to 2020 were included. We mainly observed the occurrence of graft GN between uESRD group and definitively diagnosed GN group, and repeatedly compared after propensity score matching (PSM). RESULTS: The median follow-up was 50 months in 473 KTRs, and about 75% of KTRs of native kidney disease of unknown etiology. The total cumulative incidence of graft GN was 17%, and no difference was observed between the definitively diagnosed GN group and the uESRD group (p = 0.76). Further, PSM analysis also showed no difference in the incidence of graft GN between the 2 groups. Multivariable analysis disclosed males (p = 0.001), younger age (p = 0.03), and anti-endothelial cell anti-body (AECA) positive pre-KTx (p = 0.001) were independent risk factors for graft GN. CONCLUSIONS: The incidence of graft GN was similar between uESRD and definitively diagnosed GN group. The allograft survival was also similar between two groups.


Assuntos
Glomerulonefrite , Falência Renal Crônica , Masculino , Humanos , Incidência , Estudos Retrospectivos , Glomerulonefrite/complicações , Glomerulonefrite/epidemiologia , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/cirurgia , China/epidemiologia
16.
Pharmaceuticals (Basel) ; 17(3)2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38543111

RESUMO

COVID-19, caused by SARS-CoV-2, has emerged as the most destructive emerging infectious disease of the 21st century. Vaccination is an effective method to combat viral diseases. However, due to the constant mutation of the virus, new variants may weaken the efficacy of vaccines. In the current field of new coronavirus research, viral protease inhibitors have emerged as a highly regarded therapeutic strategy. Nevertheless, existing viral protease inhibitors do not fully meet the therapeutic needs. Therefore, this paper turned to traditional Chinese medicine to explore new active compounds. This study focused on 24 isolated compounds from Acorus calamus L. and identified 8 active components that exhibited significant inhibitory effects on SARS-CoV-2 PLpro. Among these, the compound 1R,5R,7S-guaiane-4R,10R-diol-6-one demonstrated the best inhibitory activity with IC50 values of 0.386 ± 0.118 µM. Additionally, menecubebane B and neo-acorane A exhibited inhibitory activity against both Mpro and PLpro proteases, indicating their potential as dual-target inhibitors. The molecular docking results confirmed the stable conformations of these compounds with the key targets and their good activity. ADMET and Lipinski's rule analyses revealed that all the small molecule ligands possessed excellent oral absorption properties. This study provides an experimental foundation for the discovery of promising antiviral lead compounds.

17.
Pharmacol Res ; 202: 107127, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38438090

RESUMO

Circular RNAs (circRNAs) represent a novel class of non-coding RNAs that play significant roles in tumorigenesis and tumor progression. High-throughput sequencing of gastric cancer (GC) tissues has identified circRNA BIRC6 (circBIRC6) as a potential circRNA derived from the BIRC6 gene, exhibiting significant upregulation in GC tissues. The expression of circBIRC6 is notably elevated in GC patients. Functionally, it acts as a molecular sponge for miR-488, consequently upregulating GRIN2D expression and promoting GC proliferation, migration, and invasion. Moreover, overexpression of circBIRC6 leads to increased GRIN2D expression, which in turn enhances caveolin-1 (CAV1) expression, resulting in autophagy deficiency due to miR-488 sequestration. This cascade of events significantly influences tumorigenesis in vivo. Our findings collectively illustrate that the CircBIRC6-miR-488-GRIN2D axis fosters CAV1 expression in GC cells, thereby reducing autophagy levels. Both circBIRC6 and GRIN2D emerge as potential targets for treatment and independent prognostic factors for GC patients.


Assuntos
MicroRNAs , Neoplasias Gástricas , Humanos , Autofagia , Caveolina 1/genética , Caveolina 1/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Transformação Celular Neoplásica , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , MicroRNAs/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , RNA Circular/genética , RNA Circular/metabolismo , Neoplasias Gástricas/patologia
18.
Eur J Med Chem ; 268: 116252, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38422703

RESUMO

The modification based on natural products is a practical way to find anti-inflammatory drugs. In this study, 26 osthole derivatives were synthesized, and their anti-inflammatory properties were evaluated. The preliminary activity study revealed that most osthole derivatives could effectively inhibit inflammatory cytokines IL-6 secretion in LPS stimulated mouse macrophages J774A.1. Compound 7m exhibited the most effective anti-inflammatory activity (RAW264.7 IL-6 IC50: 4.57 µM, 32 times more active than osthole) in vitro with no significant influence on cell proliferation. Additionally, the mechanistic analysis demonstrated that compound 7m could block MAPK signal transduction by inhibiting the phosphorylation of JNK and p38, thereby inhibiting the release of inflammatory cytokines. Moreover, in vivo functional investigations revealed that 7m could substantially reduce DSS-induced ulcerative colitis and LPS-induced acute lung injury, with good therapeutic effects. The pharmacokinetics and acute toxicity experiments proved the safety and reliability of 7min vivo. Overall, Compound 7m could further be studied as potential anti-inflammatory candidate.


Assuntos
Lesão Pulmonar Aguda , Colite Ulcerativa , Colite , Cumarínicos , Animais , Camundongos , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Lipopolissacarídeos/farmacologia , Interleucina-6 , Reprodutibilidade dos Testes , Anti-Inflamatórios/efeitos adversos , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Citocinas , NF-kappa B , Camundongos Endogâmicos C57BL , Colite/tratamento farmacológico
19.
J Biomech ; 163: 111956, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38266534

RESUMO

This study aimed to investigate the hemodynamics of a novel fabric composite that can be used as a substitute for bovine pericardium. The structure is composed of ultrahigh molecular weight polyethylene (UHMWPE) fabric coated with thermoplastic polyurethane (TPU) membranes on both sides. In vitro experiments were carried out on two composite valve samples with different specifications and a bovine pericardial one with the same dimension and structure. Hemodynamic properties including the effective orifice area (EOA) and regurgitant fraction (RF) were obtained and compared through pulsatile-flow testing in a pulse duplicator. Using the particle image velocimetry (PIV) technique, frames of the downstream velocity field in the aortic valve chamber were captured during cardiac cycles. Then, the field of Reynolds shear stress (RSS), viscous shear stress (VSS), and turbulent kinetic energy (TKE) at peak systole were calculated. A fluid-structure interaction (FSI) model has also been used to verify the pulsatile-flow testing. Compared with the bovine pericardial valve, composite valves have nosuperiority regarding EOA and RF due to their slightly higher rigidity. However, shear stresses of composite valves were lower than those of the bovine pericardial valve indicating more stable blood flows, which means that composite leaflets have the potential to reduce the risks of thrombosis and hemolysis induced by the mechanical contact between the blood flow and leaflets of valve prostheses.


Assuntos
Próteses Valvulares Cardíacas , Animais , Bovinos , Desenho de Prótese , Hemodinâmica/fisiologia , Valva Aórtica/cirurgia , Implantação de Prótese
20.
Artigo em Inglês | MEDLINE | ID: mdl-38204237

RESUMO

BACKGROUND: Podocyte injury and inflammatory response are the core contributors to the pathogenesis of diabetic nephropathy. This study aims to identify novel regulatory miRNAs and elucidate their underlying mechanisms, which will help us understand the pathogenesis of diabetic nephropathy more comprehensively. MATERIALS AND METHODS: Different glucose concentrations were used to treat podocytes to mimic the pathology of diabetic nephropathy in vitro. Flow cytometry was used to determine cell apoptosis. Inflammatory cytokines released by podocytes were measured by using an enzymelinked immunosorbent assay (ELISA). Western Blot was used to detect the expression of PRKAB2 protein in podocytes. RESULTS: Genecard and g: profiler results revealed that miR-29b might be involved in regulating HG-induced cell injury. QRT-PCR indicated that HG-induced downregulation of miR-29b in podocytes. MiR-29b knockdown promoted cell apoptosis and inflammatory response in podocytes. MiR-29b overexpression repressed cell apoptosis and inflammatory response induced by high glucose treatment in podocytes. Luciferase reporter assay and Western Blot showed that miR-29b targeted PRKAB2 to negatively regulate PRKAB2 expression directly. Knockdown of PRKAB2 reversed the increased cell apoptosis and inflammation induced by miR-29b inhibitors. CONCLUSION: MiR-29b plays a role in inhibiting inflammation and apoptosis in high glucose (HG) treated podocytes by negatively regulating PRKAB2 expression. This study provides new potential targets and ideas for the treatment of diabetic nephropathy.


Assuntos
Apoptose , Nefropatias Diabéticas , Regulação para Baixo , Glucose , Inflamação , MicroRNAs , Podócitos , Podócitos/metabolismo , Podócitos/patologia , Podócitos/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , MicroRNAs/genética , MicroRNAs/metabolismo , Glucose/toxicidade , Inflamação/metabolismo , Inflamação/genética , Inflamação/patologia , Regulação para Baixo/efeitos dos fármacos , Animais , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/genética , Camundongos , Linhagem Celular , Humanos , Mediadores da Inflamação/metabolismo
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