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1.
Nat Commun ; 15(1): 6556, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39095386

RESUMO

The migratory insertion of metal-hydride into alkene has allowed regioselective access to organometallics, readily participating in subsequent functionalization as one conventional pathway of hydroalkylation, whereas analogous process with feedstock alkyne is drastically less explored. Among few examples, the regioselectivity of metal-hydride insertion is mostly governed by electronic bias of alkynes. To alter the regioselectivity and drastically expand the intermediate pools that we can access, one aspirational design is through alternative nickel-alkyl insertion, providing opposite regioselectivity induced by steric demand. Leveraging in situ formed nickel-alkyl species, we herein report the regio- and enantioselective hydroalkylation of alkynes with broad functional group tolerance, excellent regio- and enantioselectivity, enabling efficient route to diverse valuable chiral allylic amines motifs. Preliminary mechanistic studies indicate the aminoalkyl radical species can participate in metal-capture and lead to formation of nickel-alkyl, of which the migratory insertion is key to reverse regioselectivity observed in metal-hydride insertion.

2.
Int J Numer Method Biomed Eng ; : e3862, 2024 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-39142807

RESUMO

Surgery of jawbones has a high potential risk of causing complications associated with temporomandibular joint disorder (TMD). The objective of this study was to investigate the effects of two drive modeling methods on the biomechanical behavior of the temporomandibular joint (TMJ) including articular disc during mandibular movements. A finite element (FE) model from a healthy human computed tomography was used to evaluate TMJ dynamic using two methods, namely, a conventional spatial-oriented method (displacement-driven) and a compliant muscle-initiated method (masticatory muscle-driven). The same virtual FE model was 3D printed and a custom designed experimental platform was established to validate the accuracy of experimental and theoretical results of the TMJ biomechanics during mandibular movements. The results show that stress distributed to TMJ and articular disc from mandibular movements provided better representation from the muscle-driving approach than those of the displacement-driven modeling. The simulation and experimental data exhibited significant strong correlations during opening, protrusion, and laterotrusion (with canonical correlation coefficients of 0.994, 0.993, and 0.932, respectively). The use of muscle-driven modeling holds promise for more accurate forecasting of stress analysis of TMJ and articular disc during mandibular movements. The compliant approach to analyze TMJ dynamics would potentially contribute to clinic diagnosis and prediction of TMD resulting from occlusal disease and jawbone surgery such as orthognathic surgery or tumor resection.

3.
J Clin Anesth ; 98: 111585, 2024 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-39153353

RESUMO

STUDY OBJECTIVE: The association between early childhood exposure to general anesthesia and subsequent risk of developing attention-deficit/hyperactivity disorder remains unknown. DESIGN: A systematic review and meta-analysis of cohort studies. PATIENTS: Children undergoing general anesthesia. INTERVENTIONS: A comparison of any type of general anesthesia exposure, including total intravenous anesthesia, inhalation general anesthesia, and combined intravenous and inhaled anesthesia, with non-anesthetic exposures, which did not receive any exposure to anesthetic drugs, including general anesthetics as well as local anesthetics. MEASUREMENTS: The primary outcome measure was the risk of developing attention-deficit/hyperactivity disorder after general anesthesia exposure. MAIN RESULTS: The results of the overall meta-analysis showed an increased risk of subsequent attention-deficit/hyperactivity disorder in children exposed to general anesthesia (RR = 1.26, 95% CI, 1.16-1.38; P < 0.001; I2 = 44.6%). Subgroup analysis found that a single exposure to general anesthesia in childhood was associated with an increased risk of developing attention-deficit/hyperactivity disorder (RR = 1.29, 95% CI, 1.19-1.40, P < 0.001; I2 = 2.6%), and the risk of attention-deficit/hyperactivity disorder was further increased after multiple general anesthesia exposures (RR = 1.61, 95% CI, 1.32-1.97, P < 0.001; I2 = 57.6%). Exposure to general anesthesia lasting 1-60 min during childhood is associated with an increased risk of attention-deficit/hyperactivity disorder (ADHD) (RR: 1.38, 95% CI: 1.26-1.51, P < 0.001; I2 = 0.0%). Moreover, with longer durations of exposure (61-120 min), the risk further rises (RR: 1.55, 95% CI: 1.21-1.99, P = 0.001; I2 = 37.8%). However, no additional increase in ADHD risk was observed with exposures exceeding 120 min (RR: 1.55, 95% CI: 1.35-1.79, P < 0.001; I2 = 0.0%). CONCLUSIONS: Exposure to general anesthesia during early childhood increases the risk of developing attention-deficit/hyperactivity disorder. In particular, multiple general anesthesia exposures and exposures longer than 60 min significantly increase the risk of developing ADHD.

4.
BMC Oral Health ; 24(1): 990, 2024 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-39180031

RESUMO

BACKGROUND: The purpose of this in vitro study was to compare and evaluate the stress distribution of maxillary first premolar residual crowns restored with post-core crowns, endocrowns and inlay crowns after deep margin elevation, to explore the fitting restoration for residual crowns using finite element analysis. METHODS: A healthy complete right maxillary first premolar from a male adult was scanned by cone beam computed tomography (CBCT). The finite element model of the tooth was established by reverse engineering software such as Mimics, Geomagic and Hypermesh. On this basis, the residual crown model after deep margin elevation was made, and the experimental group models were divided into three groups, those restored with post core crowns, endocrowns and inlay crowns. Vertical and oblique static loads were applied to the experimental models to simulate the force on the tooth during mastication (the loading position was located in the central fossa of the occipital surface, and the load was 100 N) using Abaqus software. RESULTS: The peak value and distribution of von Mises stress in each part of the experimental model were observed. After deep margin elevation, the peak dentin von Mises stresses were lower than the tensile strength of normal dentin in the post-core crown, endocrown, and inlay crown groups; the lowest stress results were found in the post-core crown group for the dentin, restoration, enamel, and deep margin elevation (DME) layers under vertical and oblique loading. In terms of stress distribution clouds, the peak stresses in the dentin tissue were located in the apical 1/3 of the root after postcore crown restorations for both loads, while stress concentrations were evident in the cervical and root areas after endocrown and inlay crown restorations; regardless of the load and restoration method, the corresponding stress concentration areas appeared at the junction of the DME and dentin tissue at the loading site of the restorations; CONCLUSIONS: Post-core crowns, endocrowns and inlay crowns can be used to restore residual crowns after deep margin elevation, and post-core crowns can better protect the residual tooth tissue.


Assuntos
Dente Pré-Molar , Coroas , Análise de Elementos Finitos , Técnica para Retentor Intrarradicular , Humanos , Masculino , Fenômenos Biomecânicos , Tomografia Computadorizada de Feixe Cônico/métodos , Restaurações Intracoronárias , Análise do Estresse Dentário/métodos , Adulto , Maxila , Dentina/diagnóstico por imagem , Técnicas In Vitro , Planejamento de Prótese Dentária , Estresse Mecânico , Resistência à Tração , Relevância Clínica
5.
Front Microbiol ; 15: 1435765, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39040905

RESUMO

Introduction: Fengxiangxing Huairang Daqu (FHD) is one of the major types of Daqu in China. However, the relationship between the microbial community structure at different stages, the changes in the sensory characteristics, fermentation characteristics, volatiles, the most critical process point, and the quality formation of FHD is not clear. Methods: Based on microscopic characterization, PacBio SMRT sequencing, and HS-SPME-GC-MS volatile metabolite analysis revealed the relationship between FHD quality formation and the dynamics of Qupi. Results: The results showed that the 12th day of the culture was the most critical process point, highlighting the most significant differences in microbial community structure, sensory characteristics, fermentation characteristics, and flavor substances. Bacillus licheniformis (43.25%), Saccharopolyspora rectivirgula (35.05%), Thermoascus aurantiacus (76.51%), Aspergillus amstelodami (10.81%), and Saccharomycopsis fibuligera (8.88%) were the dominant species in FHD. S. fibuligera, A. amstelodami, and T. aurantiacus were associated with the snow-white color of the FHD epidermis, the yellow color of the interior, and the gray-white color, respectively. The abundance of T. aurantiacus, A. amstelodami, B. licheniformis, and S. rectivirgula was positively associated with the esterifying power and liquefying power of FHD. The abundance of T. aurantiacus and A. amstelodami was positively correlated with the saccharifying power of FHD. The abundance of S. fibuligera was positively related to the fermenting power of FHD. A total of 248 volatiles were detected in Qupi, mainly including alcohols, esters, aldehydes, and ketones. Of them, eleven volatiles had a significant effect on the flavor of Qupi, such as 1-butanol-3-methyl-, hydrazinecarboxamide, ethanol, phenylethyl alcohol, ethyl acetate, 2-octanone, 1-octen-3-ol, formic acid-hexyl ester, (E)-2-octen-1-ol, ethyl hexanoate, and 2(3H)-furanone-dihydro-5-pentyl-. The abundance of B. licheniformis, S. rectivirgula, T. aurantiacus, and S. fibuligera was positively correlated with the alcohols, aromatic compounds, and phenols in FHD. The abundance of S. fibuligera was positively correlated with the acids, esters, and hydrocarbons in FHD. Discussion: These results indicate important theoretical basis and technical support for controllable adjustment of FHD microbial community structure, stable control of FHD quality, and precise, effective, and large-scale guidance of FHD production.

6.
Cortex ; 178: 190-200, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39018955

RESUMO

OBJECTIVE: This study sought to characterize resting-state functional connectivity (rsFC) patterns of the hypothalamic and extrahypothalamic nuclei in craniopharyngioma (CP) patients, and to investigate potential correlations between hypothalamic and extrahypothalamic rsFC maps and neurocognitive performance. METHODS: Ninety-two CP patients and 40 demographically-matched healthy controls were included. Whole-brain seed-to-voxel analyses were used to test for between-group rsFC differences, and regression analyses were used to correlate neurocognitive performance with voxel-wise hypothalamic and extrahypothalamic rsFC maps for CP patients. Finally, spectral DCM analysis was used to explore the hypothalamus circuit associated with neurocognitive performance. RESULTS: The seed-to-voxel analyses demonstrated that the hypothalamic nuclei showed mainly significant rsFC reduction in brain areas overlayed with the cortical regions of default mode network (DMN), notably in the bilateral anterior cingulate cortices and posterior cingulate cortices. The extrahypothalamic nuclei showed significant rsFC reduction in the limbic system of bilateral caudate nuclei, corpus callosum, fornix, and thalamus. Regression analyses revealed that worse cognitive performance was correlated with abnormal hypothalamic rsFC with brain areas in DMN, and DCM analysis revealed a hypothalamus-DMN circuit responsible for functional modulation of cognitive impairment in CP patients. CONCLUSIONS: Our study demonstrated that CPs invading into hypothalamus impacted hypothalamic and extrahypothalamic rsFC with brain areas of DMN and limbic system, the severity of which was parallel with the grading system of hypothalamus involvement. In addition to the CP-induced structural damage to the hypothalamus alone, abnormal functional connectivity within the hypothalamus-DMN circuit might be a functional mechanism leading to the cognitive impairment in CP patients.

7.
Materials (Basel) ; 17(14)2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-39063745

RESUMO

As an important part of die steels, hot-work die steels are mainly used to manufacture molds made of solid metal or high-temperature liquid metal from heating to recrystallization temperature. In view of the requirements for mechanical properties and service life for hot-work die steel, it is conducive to improve the thermal fatigue resistance, wear resistance, and oxidation resistance of hot work die steel. In this review, the main failure modes of hot-work die steel were analyzed. Four traditional methods of strengthening and toughening die steel were summarized, including optimizing alloying elements, electroslag remelting, increasing the forging ratio, and heat treatment process enhancement. A new nano-strengthening method was introduced that aimed to refine the microstructure of hot-work abrasive steel and improve its service performance by adding nanoparticles into molten steel to achieve uniform dispersion. This review provides an overview to improve the service performance and service life of hot work die steel.

8.
Sci Total Environ ; 949: 175162, 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39084372

RESUMO

Improper disposal of organic solid waste results in serious environmental pollution. Aerobic composting provides an environmentally friendly treatment method, but improving humification of raw materials remains a challenge. This study revealed the effect of different concentrations of potassium persulfate (PP) on humification of chicken manure and straw aerobic composting and the underlying microbial mechanisms. The results showed that when 0.6 % PP was added (PPH group), humus and the degree of polymerization were 80.77 mg/g and 2.52, respectively, which were significantly higher than those in 0.3 % PP (PPL group). As the concentration of PP was increased, the composition of rare taxa (RT) changed and improved in evenness, while abundant taxa (AT) was unaffected. Additionally, the density (0.037), edges (3278), and average degree (15.21) in the co-occurrence network decreased compared to PPL, while the average path (4.021) and modularity increased in PPH. This resulted in facilitating the turnover of matter, information, and energy among the microbes. Interestingly, cooperative behavior between microorganisms during the maturation period (24-60 d) occurred in PPH, but competitive relationships dominated in PPL. Cooperative behavior was positively correlated with humus (p < 0.05). Because the indices, such as higher degree, betweenness centrality, eigenvector centrality, and closeness centrality of the AT, were located in the microbial network center compared to RT, they were unaffected by the concentration of PP. The abundance of carbohydrate and amino acid metabolic pathways, which play an important role in humification, were higher in PPH. These findings contribute to understanding the relative importance of composition, interactions, and metabolic functionality of RT and AT on humification during chicken manure and straw aerobic composting under different concentrations of PP, as well as provide a basic reference for use of various conditioning agents to promote humification of organic solid waste.


Assuntos
Galinhas , Compostagem , Esterco , Microbiota , Compostos de Potássio , Sulfatos , Animais , Microbiota/efeitos dos fármacos , Substâncias Húmicas , Microbiologia do Solo
9.
Front Chem ; 12: 1406051, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38860236

RESUMO

This study introduces newly discovered chrysin derivatives that show potential as candidate molecules for treating inflammatory bowel disease (IBD). Compound 4b, among the synthesized compounds, displayed significant inhibitory effects on monocyte adhesion to colon epithelium induced by TNF-α, with an IC50 value of 4.71 µM. Further mechanistic studies demonstrated that 4b inhibits the production of reactive oxygen species (ROS) and downregulates the expression of ICAM-1 and MCP-1, key molecules involved in monocyte-epithelial adhesion, as well as the transcriptional activity of NF-κB. In vivo experiments have shown that compound 4b exhibits a dose-dependent inhibition of 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)-induced colitis in rats, thereby validating its effectiveness as a colitis inhibitor in animal models. These results indicate that 4b shows considerable promise as a therapeutic agent for managing IBD.

10.
Int J Biol Macromol ; 273(Pt 1): 132877, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38848847

RESUMO

In this study, 16S rDNA high-throughput sequencing, Fourier transform infrared spectroscopy, and two-dimensional correlation spectroscopy techniques were used to analyze the mechanisms driving the sequence of degradation of gummy substances by the microbial community and hydrolytic enzymes during the flax dew degumming process. The results revealed that the inoculation of combined bacteria induced quorum sensing, modulated hydrolytic enzyme production, and reshaped the community structure. Lignin-degraded genera (Pseudomonas and Sphingobacterium) were enriched, and the relative abundances of pectin- and cellulose-degraded genera (Chryseobacterium) decreased in the early degumming stages. Hemicellulose-degraded genera (Brevundimonas) increased over the degumming time. Moreover, the abundance of lignin hydrolytic enzymes improved in the early stages, while the abundance of pectin hydrolytic enzymes increased at the end of degumming. Various types of functional bacteria taxa changed the sequence of substance degradation. Electron scanning microscopy and differential scanning calorimetry results indicated that the degumming, facilitated by the inoculation of combined bacteria, was nearly completed by 21 d. The fibers exhibited smoother and more intact properties, along with higher thermal stability, as indicated by a melting temperature of 71.54 °C. This study provides a reference for selecting precise degumming bacterial agents to enhance degumming efficiency.


Assuntos
Bactérias , Linho , Bactérias/genética , Bactérias/classificação , Bactérias/metabolismo , Linho/microbiologia , Lignina/metabolismo , Lignina/química , Hidrólise , Espectroscopia de Infravermelho com Transformada de Fourier , Filogenia , RNA Ribossômico 16S/genética , Pectinas/metabolismo , Celulose/metabolismo
11.
Pol J Microbiol ; 73(2): 253-262, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38905280

RESUMO

To establish a rapid detection method for norovirus GII.2 genotype, this study employed reverse transcription recombinase polymerase amplification (RT-RPA) combined with CRISPR/Cas12a and lateral flow strip (RT-RPA-Cas12a-LFS). Here, the genome of norovirus GII.2 genotype was compared to identify highly conserved sequences, facilitating the design of RT-RPA primers and crRNA specific to the conserved regions of norovirus GII.2. Subsequently, the reaction parameters of RT-RPA were optimized and evaluated using agar-gel electrophoresis and LFS. The results indicate that the conserved sequences of norovirus GII.2 were successfully amplified through RT-RPA at 37°C for 25 minutes. Additionally, CRISPR/Cas12a-mediated cleavage detection was achieved through LFS at 37°C within 10 minutes using the amplification products as templates. Including the isothermal amplification reaction time, the total time is 35 minutes. The established RT-RPA-Cas12a-LFS method demonstrated specific detection of norovirus GII.2, yielding negative results for other viral genomes, and exhibited an excellent detection limit of 10 copies/µl. The RT-RPA-Cas12a-LFS method was further compared with qRT-PCR by analyzing 60 food-contaminated samples. The positive conformity rate was 100%, the negative conformity rate was 95.45%, and the overall conformity rate reached 98.33%. This detection method for norovirus GII.2 genotype is cost-effective, highly sensitive, specific, and easy to operate, offering a promising technical solution for field-based detection of the norovirus GII.2 genotype.


Assuntos
Genótipo , Norovirus , Norovirus/genética , Norovirus/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico/métodos , Sistemas CRISPR-Cas , Humanos , RNA Viral/genética , Infecções por Caliciviridae/virologia , Infecções por Caliciviridae/diagnóstico , Sensibilidade e Especificidade
12.
Fitoterapia ; 177: 106048, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38838825

RESUMO

Four new phenols and one new aminobenzoic acid derivative, with five known phenols were isolated from the roots of Rhus chinensis Mill. Their structures were elucidated by UV, IR, HRESIMS, 1D and 2D NMR spectra, as well as optical rotations. Compound 4 significantly inhibited mouse ear inflammation (inhibitory rate of 44.03%), and significantly extended the time of pain response (extension rate of 48.55%), showing significant anti-inflammatory and analgesic effects in vivo.


Assuntos
Analgésicos , Anti-Inflamatórios , Fenóis , Raízes de Plantas , Rhus , Animais , Raízes de Plantas/química , Camundongos , Estrutura Molecular , Fenóis/isolamento & purificação , Fenóis/farmacologia , Fenóis/química , Rhus/química , Analgésicos/farmacologia , Analgésicos/isolamento & purificação , Analgésicos/química , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Masculino , Dor/tratamento farmacológico , Dor/induzido quimicamente , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , Inflamação/tratamento farmacológico , China
13.
Cancer Cell Int ; 24(1): 222, 2024 Jun 27.
Artigo em Inglês | MEDLINE | ID: mdl-38937761

RESUMO

Triple negative breast cancer (TNBC) is a type of cancer that lacks receptor expression and has complex molecular mechanisms. Recent evidence shows that the ubiquitin-protease system is closely related to TNBC. In this study, we obtain a key ubiquitination regulatory substrate-ABI2 protein by bioinformatics methods, which is also closely related to the survival and prognosis of TNBC. Further, through a series of experiments, we demonstrated that ABI2 expressed at a low level in TNBC tumors, and it has the ability to control cell cycle and inhibit TNBC cell migration, invasion and proliferation. Molecular mechanism studies proved E3 ligase CBLC could increase the ubiquitination degradation of ABI2 protein. Meanwhile, RNA-seq and IP experiments indicated that ABI2, acting as a crucial factor of tumor suppression, can significantly inhibit PI3K/Akt signaling pathway via the interaction with Rho GTPase RAC1. Finally, based on TNBC drug target ABI2, we screened and found that FDA-approved drug Colistimethate sodium(CS) has significant potential in suppressing the proliferation of TNBC cells and inducing cell apoptosis, making it a promising candidate for impeding the progression of TNBC.

14.
Biomater Adv ; 161: 213899, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38772133

RESUMO

Large bone defects, particularly those exceeding the critical size, present a clinical challenge due to the limited regenerative capacity of bone tissue. Traditional treatments like autografts and allografts are constrained by donor availability, immune rejection, and mechanical performance. This study aimed to develop an effective solution by designing gradient gyroid scaffolds with titania (TiO2) surface modification for the repair of large segmental bone defects. The scaffolds were engineered to balance mechanical strength with the necessary internal space to promote new bone formation and nutrient exchange. A gradient design of the scaffold was optimized through Finite Element Analysis (FEA) and Computational Fluid Dynamics (CFD) simulations to enhance fluid flow and cell adhesion. In vivo studies in rabbits demonstrated that the G@TiO2 scaffold, featuring a gradient structure and TiO2 surface modification, exhibited superior healing capabilities compared to the homogeneous structure and TiO2 surface modification (H@TiO2) and gradient structure (G) scaffolds. At 12 weeks post-operation, in a bone defect representing nearly 30 % of the total length of the radius, the implantation of the G@TiO2 scaffold achieved a 27 % bone volume to tissue volume (BV/TV) ratio, demonstrating excellent osseointegration. The TiO2 surface modification provided photothermal antibacterial effects, enhancing the scaffold's biocompatibility and potential for infection prevention. These findings suggest that the gradient gyroid scaffold with TiO2 surface modification is a promising candidate for treating large segmental bone defects, offering a combination of mechanical strength, bioactivity, and infection resistance.


Assuntos
Ligas , Propriedades de Superfície , Alicerces Teciduais , Titânio , Titânio/química , Animais , Coelhos , Alicerces Teciduais/química , Ligas/química , Regeneração Óssea/efeitos dos fármacos , Osseointegração/efeitos dos fármacos , Osso e Ossos , Engenharia Tecidual/métodos , Análise de Elementos Finitos , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia
16.
Phytochemistry ; 224: 114148, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38763311

RESUMO

Seven previously undescribed triterpenes (1-7), as well as one triterpene (8) previously described as a synthetic product, were isolated from the antler-shaped fruiting body of Ganoderma lucidum. Their structures were established based on comprehensive spectroscopy analysis. At a concentration of 10 µM, (24E)-3-oxo-15α-acetoxy-lanosta-7,9(11),24-trien-26-al (3) and (24R,25S)-3-oxo-lanosta-7,9(11)-dien-25-ethoxyl-24,26-diol (5) provided significant protection against acetaminophen-induced necrosis in human HepG2 liver cancer cells, and the cell survival rates were 69.7 and 76.1% respectively, similar to that of the positive control (glutathione, 72.1%). Based on the present results, these compounds could be potential hepatoprotective agents.


Assuntos
Carpóforos , Substâncias Protetoras , Reishi , Triterpenos , Triterpenos/farmacologia , Triterpenos/química , Triterpenos/isolamento & purificação , Humanos , Células Hep G2 , Carpóforos/química , Reishi/química , Substâncias Protetoras/farmacologia , Substâncias Protetoras/química , Substâncias Protetoras/isolamento & purificação , Estrutura Molecular , Sobrevivência Celular/efeitos dos fármacos , Acetaminofen/farmacologia , Relação Estrutura-Atividade , Fígado/efeitos dos fármacos , Relação Dose-Resposta a Droga
17.
PLoS One ; 19(5): e0303156, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38709746

RESUMO

BACKGROUND: Parkinson's disease (PD) patients face a substantial unmet need for disease-modifying interventions. Potential approaches such as exercise and acupuncture have been investigated to slow PD progression. To address this unmet need, we developed a novel therapeutic approach that integrates acupuncture and exercise: the Meridian Activation Remedy System for PD patients (MARS-PD). Building upon promising outcomes observed in our preliminary pilot study, where MARS-PD exhibited a large clinically important difference on the Movement Disorder Society Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS Part III), we embark on a randomized controlled trial with the primary objective of examining the efficacy, safety, and economic impact of MARS-PD. METHODS: In this single-center, assessor and statistician-blinded, parallel-group randomized controlled trial, we aim to investigate the clinical efficacy of MARS-PD through 16 interventions administered over 8 weeks in 88 PD patients. Participants will be randomly assigned to the experimental (n = 44) or control (n = 44) groups. The experimental group will receive MARS-PD intervention alongside standard care, while the control group will solely receive standard care. The intervention period spans 8 weeks, followed by a 12-week post-intervention follow-up. The primary endpoint is the change in MDS-UPDRS Part III score from baseline to the conclusion of the 8-week intervention. Secondary outcomes encompass various assessments, including MDS-UPDRS, International Physical Activity Questionnaire Short Form, Parkinson Self Questionnaire, Parkinson's Disease Sleep Scale, Timed Up and Go test, GAITRite metrics, Functional Near-Infrared Spectroscopy measurements, smart band outcomes, gut microbiome analysis results, and iris connective tissue texture. DISCUSSION: Previous studies by the authors have indicated MARS-PD's safety and benefits for PD patients. Building upon this foundation, our current study aims to provide a more comprehensive and detailed confirmation of the efficacy of MARS-PD. TRIAL REGISTRATION: cris.nih.go.kr KCT0006646 -First posted on 7 October 2021; ClinicalTrials.gov NCT05621772 -First posted on 11 November 2022.


Assuntos
Doença de Parkinson , Humanos , Doença de Parkinson/terapia , Masculino , Feminino , Meridianos , Pessoa de Meia-Idade , Terapia por Acupuntura/métodos , Terapia por Acupuntura/efeitos adversos , Idoso , Resultado do Tratamento , Adulto , Método Simples-Cego , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia por Exercício/métodos
18.
Cell Death Dis ; 15(4): 289, 2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38653973

RESUMO

GATA-binding protein 4 (GATA4) is recognized for its significant roles in embryogenesis and various cancers. Through bioinformatics and clinical data, it appears that GATA4 plays a role in breast cancer development. Yet, the specific roles and mechanisms of GATA4 in breast cancer progression remain elusive. In this study, we identify GATA4 as a tumor suppressor in the invasion and migration of breast cancer. Functionally, GATA4 significantly reduces the transcription of MMP9. On a mechanistic level, GATA4 diminishes MMP9 transcription by interacting with p65 at the NF-κB binding site on the MMP9 promoter. Additionally, GATA4 promotes the recruitment of HDAC1, amplifying the bond between p65 and HDAC1. This leads to decreased acetylation of p65, thus inhibiting p65's transcriptional activity on the MMP9 promoter. Moreover, GATA4 hampers the metastasis of breast cancer in vivo mouse model. In summary, our research unveils a novel mechanism wherein GATA4 curtails breast cancer cell metastasis by downregulating MMP9 expression, suggesting a potential therapeutic avenue for breast cancer metastasis.


Assuntos
Neoplasias da Mama , Movimento Celular , Fator de Transcrição GATA4 , Regulação Neoplásica da Expressão Gênica , Histona Desacetilase 1 , Metaloproteinase 9 da Matriz , Invasividade Neoplásica , Humanos , Fator de Transcrição GATA4/metabolismo , Fator de Transcrição GATA4/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Feminino , Movimento Celular/genética , Histona Desacetilase 1/metabolismo , Histona Desacetilase 1/genética , Animais , Acetilação , Linhagem Celular Tumoral , Camundongos , Fator de Transcrição RelA/metabolismo , Transcrição Gênica , Regiões Promotoras Genéticas/genética , Camundongos Nus , Camundongos Endogâmicos BALB C
19.
J Nutr Biochem ; 130: 109649, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38642842

RESUMO

Obesity and its related metabolic diseases bring great challenges to public health. In-depth understanding on the efficacy of weight-loss interventions is critical for long-term weight control. Our study demonstrated the comparable efficacy of exercise (EX), intermittent fasting (IF), or the change of daily diet from an unhealthy to a normal chow (DR) for weight reduction, but largely divergently affected metabolic status and transcriptome of subcutaneous fat, scapular brown fat, skeletal muscles and liver in high-fat-high-fructose diet (HFHF) induced obese mice. EX and IF reduced systematic inflammation, improved glucose and lipid metabolism in liver and muscle, and amino acid metabolism and thermogenesis in adipose tissues. EX exhibited broad regulatory effects on TCA cycle, carbon metabolism, thermogenesis, propanoate-, fatty acid and amino acid metabolism across multiple tissues. IF prominently affected genes involved in mitophagy and autophagy in adipose tissues and core genes involved in butanoate metabolism in liver. DR, however, failed to improve metabolic homeostasis and biological dysfunctions in obese mice. Notably, by exploring potential inter-organ communication, we identified an obesity-resistant-like gene profile that were strongly correlated with HFHF induced metabolic derangements and could predict the degree of weight regain induced by the follow-up HFHF diet. Among them, 12 genes (e.g., Gdf15, Tfrc, Cdv3, Map2k4, and Nqo1) were causally associated with human metabolic traits, i.e., BMI, body fat mass, HbA1C, fasting glucose, and cholesterol. Our findings provide critical groundwork for improved understanding of the impacts of weight-loss interventions on host metabolism. The identified genes predicting weight regain may be considered regulatory targets for improving long-term weight control.


Assuntos
Jejum , Homeostase , Camundongos Endogâmicos C57BL , Obesidade , Transcriptoma , Aumento de Peso , Redução de Peso , Animais , Masculino , Obesidade/metabolismo , Obesidade/dietoterapia , Dieta Hiperlipídica/efeitos adversos , Condicionamento Físico Animal , Camundongos , Fígado/metabolismo , Músculo Esquelético/metabolismo , Termogênese , Metabolismo dos Lipídeos , Tecido Adiposo/metabolismo , Jejum Intermitente
20.
Zhongguo Zhong Yao Za Zhi ; 49(3): 763-769, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621880

RESUMO

This study aims to investigate the effect of Erchen Decoction(ECD) on liver mitochondrial function in mice with a high-fat diet and its possible mechanism. A total of sixty C57BL/6J mice were randomly divided into a normal group, high-fat group, ECD group, mTORC1 activator(MHY) group, ECD+MHY group, and polyene phosphatidyl choline(PPC) group, with 10 rats in each group. The normal group was given a normal diet, and the other groups were fed a high-fat diet for 20 weeks. At the 17th week, the ECD group and ECD+MHY group were given ECD(8.7 g·kg~(-1)) daily, and the PPC group was given PPC(0.18 g·kg~(-1)) daily, while the remaining groups were given normal saline(0.01 mL·g~(-1)) daily for four weeks. In the 19th week, the MHY group and ECD+MHY group were injected intraperitoneally with MHY(5 mg·kg~(-1)) every other day for two weeks. During the experiment, the general conditions of the mice were observed. The contents of triglyceride(TG) and total cholesterol(TC) in serum were measured. Morphological changes in liver tissue were examined through HE and oil red O staining. The content of adenosine triphosphate(ATP) was determined using chemiluminescence, and mitochondrial membrane potential was assessed using a fluorescence probe(JC-1). Western blot was performed to detect the expression of rapamycin target protein complex 1(mTOR1), ribosomal protein S6 kinase B1(S6K), sterol regulatory element binding protein 1(SREBP1), and caveolin 1(CAV1). RESULTS:: revealed that compared with the normal group, the mice in the high-fat group exhibited significant increases in body weight and abdominal circumference(P<0.01). Additionally, there were significant increases in TG and TC levels(P<0.01). HE and oil red O staining showed that the boundaries of hepatic lobules were unclear; hepatocytes were enlarged, round, and irregularly arranged, with obvious lipid droplet deposition and inflammatory cell infiltration. The liver ATP content and mitochondrial membrane potential decreased significantly(P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 increased significantly(P<0.01), while the expression of CAV1 decreased significantly(P<0.01). Compared with the high-fat group, the body weight and TG content of mice in the ECD group and PPC group decreased significantly(P<0.05). Improvements were observed in hepatocyte morphology, lipid deposition, and inflammatory cell infiltration. Furthermore, there were significant increases in ATP content and mitochondrial membrane potential(P<0.05 or P<0.01). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly in the ECD group(P<0.01), while CAV1 expression increased significantly(P<0.01). However, the indices mentioned above did not show improvement in the MHY group. When the ECD+MHY group was compared with the MHY group, there were significant reductions in body weight and TG contents(P<0.05). The morphological changes of hepatocytes, lipid deposition, and inflammatory cell infiltration were recovered. Moreover, there were significant increases in liver ATP content and mitochondrial membrane potential(P<0.05 or P<0.05). The expression of p-mTOR, p-S6K, and n-SREBP1 decreased significantly(P<0.01), while CAV1 expression increased significantly(P<0.01). In conclusion, ECD can improve mitochondrial function by regulating the mTORC1/SREBP1/CAV1 pathway. This mechanism may be involved in the resolution of phlegm syndrome and the regulation of lipid metabolism.


Assuntos
Compostos Azo , Dieta Hiperlipídica , Hepatopatia Gordurosa não Alcoólica , Camundongos , Ratos , Animais , Dieta Hiperlipídica/efeitos adversos , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/farmacologia , Caveolina 1/metabolismo , Caveolina 1/farmacologia , Camundongos Endogâmicos C57BL , Fígado , Hepatopatia Gordurosa não Alcoólica/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Triglicerídeos/metabolismo , Peso Corporal , Trifosfato de Adenosina/farmacologia
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