Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 443
Filtrar
1.
Int J Prosthodont ; : 1-18, 2024 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-39110959

RESUMO

Purpose: The improvement of computer-aided design and computer-aided manufacturing (CAD/CAM) has changed the methods of fabricating laminate veneers. The objectives of this study were to evaluate the marginal and internal fit of ceramic veneers manufactured with different CAD/CAM techniques. Materials and methods: A metal die was made by copying a prepared plastic maxillary central right incisor and scanned for designing a laminate veneer. One hundred laminate veneers were made with four different CAD/CAM techniques (n=25), including milled lithium disilicate (MLD), heat-pressed lithium disilicate with 3-dimensional (3D) printed wax patterns (PLD), milled zirconia (MZ), and 3Dprinted zirconia (PZ). The virtual marginal and internal fit of fabricated veneers was evaluated with digital crown fitting software. The actual marginal and internal fit was measured with the silicone replica method under a digital microscope. The measured data were analyzed using the one-way analysis of variance and the Turkey test. Results: There were significant differences in marginal and internal fit (P < 0.001) among manufacturing techniques. Both the virtual and actual marginal and internal gaps were higher in the PLD and PZ groups compared to the MLD and MZ groups. Conclusion: All four CAD/CAM techniques of manufacturing veneers, that is, milled lithium disilicate, heat-pressed lithium disilicate with 3D-printed wax patterns, milled zirconia, and 3D-printed zirconia, have clinically acceptable marginal and internal fit. Milled zirconia and lithium disilicate veneers demonstrated superior marginal and internal fit compared to 3D-printed zirconia and heat-pressed lithium disilicate veneers with 3D-printed wax patterns.

2.
Front Microbiol ; 15: 1400434, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38966389

RESUMO

Escherichia coli produces extracellular vesicles called outer membrane vesicles. In this study, we investigated the mechanism underlying the hypervesiculation of deletion mutant ΔrodZ of E. coli. RodZ forms supramolecular complexes with actin protein MreB and peptidoglycan (PG) synthase, and plays an important role in determining the cell shape. Because mreB is an essential gene, an expression-repressed strain (mreB R3) was constructed using CRISPRi, in which the expression of mreB decreased to 20% of that in the wild-type (WT) strain. In shaken-flask culture, the ΔrodZ strain produced >50 times more vesicles than the WT strain. The mreB-repressed strain mreB R3 showed eightfold higher vesicle production than the WT. ΔrodZ and mreB R3 cells were observed using quick-freeze replica electron microscopy. As reported in previous studies, ΔrodZ cells were spherical (WT cells are rod-shaped). Some ΔrodZ cells (around 7% in total) had aberrant surface structures, such as budding vesicles and dented surfaces, or curved patterns on the surface. Holes in the PG layer and an increased cell volume were observed for ΔrodZ and mreB R3 cells compared with the WT. In conditions of osmotic support using sucrose, the OD660 value of the ΔrodZ strain increased significantly, and vesicle production decreased drastically, compared with those in the absence of sucrose. This study first clarified that vesicle production by the E. coli ΔrodZ strain is promoted by surface budding and a burst of cells that became osmotically sensitive because of their incomplete PG structure.

3.
Dent Mater ; 2024 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-39060128

RESUMO

OBJECTIVES: We evaluated the mechanical properties of zirconia restorations produced via additive manufacturing (AM) and the crown accuracy of zirconia crowns. METHODS: Zirconia disks, bars, and crowns were manufactured via subtractive (CNC group) and additive manufacturing (AM group) techniques. Disk-shaped specimens in each group were autoclaved at 134 °C and 216 kPa for 5, 10, and 24 h. The phases of the specimens were analyzed using an X-ray diffractometer. The flexural strengths were measured via biaxial flexural tests. The morphologies were examined using a scanning electron microscope. The correlation between the m-phase fraction and biaxial flexural strength by autoclave time in each group was analyzed via linear mixed model and Pearson's correlation analysis. For each group, crown specimens were used to assess the marginal and internal gaps using the replica technique. Buccolingual and mesiodistal cross-sections were measured, and a repeated measures one-way ANOVA was performed. RESULTS: Linear mixed model analysis indicated that for both groups, with an increase in the autoclave time, the flexural strength decreased, whereas the m-phase fraction increased. Pearson's correlation analysis revealed no correlation between the m-phase fraction and flexural strength for either group. A repeated measures one-way ANOVA was conducted on instrumented sections (buccal, lingual, mesial, and distal), revealing that the marginal and internal gaps of AM-produced zirconia crowns were less accurate than those of CNC-produced zirconia crowns. SIGNIFICANCE: These findings suggest that additively produced zirconia restorations have mechanical properties comparable to those of conventionally produced ceramics and may be suitable for clinical applications.

4.
J Diabetes Sci Technol ; : 19322968241262112, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38887022

RESUMO

Digital twin is a new concept that is rapidly gaining recognition especially in the medical field. Indeed, being a virtual representation of real-world entities and processes, a digital twin can be used to accurately represent the patients' disease, clarify the treatment target, and realize personalized and precise therapies. However, despite being a revolutionary concept, the diffusion of digital twins in type 1 diabetes (T1D) is still limited. In this systematic review, we analyzed structure, operating conditions, and characteristics of digital twins being developed for T1D. Our search covered published documents until March 2024: 220 publications were identified, 37 of which were duplicated entries; in addition, 173 publications were removed after inspection of titles, abstracts, and keywords; and finally, 11 publications were fully reviewed, of which 8 were deemed eligible for inclusion. We found that all eight methodologies are not comprehensive multi-scale virtual replicas of the individual with T1D, but they all focus on describing glucose-insulin metabolism, aiming to simulate glucose concentration resultant from therapeutic interventions. In this review, we will compare and analyze different factors characterizing these digital twins, such as operating principles (mathematical model, twinning procedure, validation and assessment) and the key aspects for practical adoption (inclusion of physical activity, data required for twinning, open-source availability). We will conclude the paper listing which, in our opinion, are the current limitations and future directives of digital twins in T1D, hoping that this article can be helpful to researchers working on diabetes technologies to further develop the use of such an important instrument.

5.
ACS Synth Biol ; 13(7): 2029-2037, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-38885191

RESUMO

Synthetic viral nanostructures are useful as materials for analyzing the biological behavior of natural viruses and as vaccine materials. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped virus embedding a spike (S) protein involved in host cell infection. Although nanomaterials modified with an S protein without an envelope membrane have been developed, they are considered unsuitable for stability and functionality. We previously constructed an enveloped viral replica complexed with a cationic lipid bilayer and an anionic artificial viral capsid self-assembled from ß-annulus peptides. In this study, we report the first example of an enveloped viral replica equipped with an S protein derived from SARS-CoV-2. Interestingly, even the S protein equipped on the enveloped viral replica bound strongly to the free angiotensin-converting enzyme 2 (ACE2) receptor as well as ACE2 localized on the cell membrane.


Assuntos
Enzima de Conversão de Angiotensina 2 , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Glicoproteína da Espícula de Coronavírus/metabolismo , Glicoproteína da Espícula de Coronavírus/química , Enzima de Conversão de Angiotensina 2/metabolismo , Enzima de Conversão de Angiotensina 2/química , SARS-CoV-2/metabolismo , Humanos , COVID-19/virologia , Bicamadas Lipídicas/metabolismo , Bicamadas Lipídicas/química , Envelope Viral/metabolismo , Nanoestruturas/química
6.
Nutr Res ; 127: 108-122, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38943729

RESUMO

Canola meal, a by-product of processing canola into oil, reportedly contains high amounts of phenolic compounds and proteins. However, as canola meal is primarily used as feed for livestock, advances in multiple research fields are required to broaden its potential applications. Photoaging is caused by continuous exposure to ultraviolet (UV) radiation from sunlight. UV radiation generates reactive oxygen species and destroys collagen in the skin, thickening the epidermis, reducing elasticity, and causing wrinkles. We hypothesized that canola meal extract (CME) can mitigate the damage to skin associated with wrinkles induced by exposure to UVB radiation. To evaluate the anti-wrinkle effect, we administered CME orally to 40 female Hos:HR-1 hairless mice divided into 5 groups: (1) control mice, (2) a UVB group, and (3-5) CME-treated groups (CME-250, 500, and 1000 mg/kg body weight/day, respectively). All groups except the controls were irradiated with UVB 3 times a week to create wrinkles due to photoaging. CME administration inhibited the increase of the number, mean length, and mean depth of wrinkles induced by UVB radiation as assessed using a skin replica. Histopathological image analysis revealed that CME administration resulted in a decrease in epidermal thickness and an increase in collagen content, while increasing catalase activity and hydroxyproline content in skin tissues. CME administration inhibited the phosphorylation of mitogen-activated protein kinase and decreased the production of collagenase and gelatinase. These results suggest that CME, an upcycled material, has the potential to develop into a healthful and functional food ingredient with anti-wrinkling effects.


Assuntos
Biomarcadores , Camundongos Pelados , Extratos Vegetais , Envelhecimento da Pele , Pele , Raios Ultravioleta , Animais , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Feminino , Extratos Vegetais/farmacologia , Pele/efeitos da radiação , Pele/efeitos dos fármacos , Pele/metabolismo , Biomarcadores/metabolismo , Camundongos , Colágeno/metabolismo , Brassica napus/química
7.
Network ; : 1-28, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771196

RESUMO

Effective management of data is a major issue in Distributed File System (DFS), like the cloud. This issue is handled by replicating files in an effective manner, which can minimize the time of data access and elevate the data availability. This paper devises a Fractional Social Optimization Algorithm (FSOA) for replica management along with balancing load in DFS in the cloud stage. Balancing the workload for DFS is the main objective. Here, the chunk creation is done by partitioning the file into a different number of chunks considering Deep Fuzzy Clustering (DFC) and then in the round-robin manner the Virtual machine (VM) is assigned. In that case for balancing the load considering certain objectives like resource use, energy consumption and migration cost thereby the load balancing is performed with the proposed FSOA. Here, the FSOA is formulated by uniting the Social optimization algorithm (SOA) and Fractional Calculus (FC). The replica management is done in DFS using the proposed FSOA by considering the various objectives. The FSOA has the smallest load of 0.299, smallest cost of 0.395, smallest energy consumption of 0.510, smallest overhead of 0.358, and smallest throughput of 0.537.

8.
Biomimetics (Basel) ; 9(5)2024 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-38786465

RESUMO

Every year, almost 4 million patients received medical care for knee osteoarthritis. Osteoarthritis involves progressive deterioration or degenerative changes in the cartilage, leading to inflammation and pain as the bones and ligaments are affected. To enhance treatment and surgical outcomes, various studies analyzing the biomechanics of the human skeletal system by fabricating simulated bones, particularly those reflecting the characteristics of patients with knee osteoarthritis, are underway. In this study, we fabricated replicated bones that mirror the bone characteristics of patients with knee osteoarthritis and developed a skeletal model that mimics the actual movement of the knee. To create patient-specific replicated bones, models were extracted from computerized tomography (CT) scans of knee osteoarthritis patients. Utilizing 3D printing technology, we replicated the femur and tibia, which bear the weight of the body and support movement, and manufactured cartilage capable of absorbing and dispersing the impact of knee joint loads using flexible polymers. Furthermore, to implement knee movement in the skeletal model, we developed artificial muscles based on shape memory alloys (SMAs) and used them to mimic the rolling, sliding, and spinning motions of knee flexion. The knee movement was investigated by changing the SMA spring's position, the number of coils, and the applied voltage. Additionally, we developed a knee-joint-mimicking system to analyze the movement of the femur. The proposed artificial-skeletal-model-based knee-joint-mimicking system appears to be applicable for analyzing skeletal models of knee patients and developing surgical simulation equipment for artificial joint replacement surgery.

9.
Biochem Biophys Res Commun ; 712-713: 149945, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38640732

RESUMO

ORF3b is one of the SARS-CoV-2 accessory proteins. Previous experimental study suggested that ORF3b prevents IRF3 translocating to nucleus. However, the biophysical mechanism of ORF3b-IRF3 interaction is elusive. Here, we explored the conformation ensemble of ORF3b using all-atom replica exchange molecular dynamics simulation. Disordered ORF3b has mixed α-helix, ß-turn and loop conformers. The potential ORF3b-IRF3 binding modes were searched by docking representative ORF3b conformers with IRF3, and 50 ORF3b-IRF3 complex poses were screened using molecular dynamics simulations ranging from 500 to 1000 ns. We found that ORF3b binds IRF3 predominantly on its CBP binding and phosphorylated pLxIS motifs, with CBP binding site has the highest binding affinity. The ORF3b-IRF3 binding residues are highly conserved in SARS-CoV-2. Our results provided biophysics insights into ORF3b-IRF3 interaction and explained its interferon antagonism mechanism.


Assuntos
Fator Regulador 3 de Interferon , Simulação de Dinâmica Molecular , Ligação Proteica , SARS-CoV-2 , Fator Regulador 3 de Interferon/metabolismo , Fator Regulador 3 de Interferon/química , SARS-CoV-2/metabolismo , SARS-CoV-2/química , Humanos , Sítios de Ligação , COVID-19/virologia , COVID-19/metabolismo , Simulação de Acoplamento Molecular , Proteínas Virais Reguladoras e Acessórias/metabolismo , Proteínas Virais Reguladoras e Acessórias/química , Conformação Proteica
10.
Proc Natl Acad Sci U S A ; 121(15): e2317197121, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38579011

RESUMO

Riboswitches are messenger RNA (mRNA) fragments binding specific small molecules to regulate gene expression. A synthetic N1 riboswitch, inserted into yeast mRNA controls the translation of a reporter gene in response to neomycin. However, its regulatory activity is sensitive to single-point RNA mutations, even those distant from the neomycin binding site. While the association paths of neomycin to N1 and its variants remain unknown, recent fluorescence kinetic experiments indicate a two-step process driven by conformational selection. This raises the question of which step is affected by mutations. To address this, we performed all-atom two-dimensional replica-exchange molecular dynamics simulations for N1 and U14C, U14C[Formula: see text], U15A, and A17G mutants, ensuring extensive conformational sampling of both RNA and neomycin. The obtained neomycin association and binding paths, along with multidimensional free-energy profiles, revealed a two-step binding mechanism, consisting of conformational selection and induced fit. Neomycin binds to a preformed N1 conformation upon identifying a stable upper stem and U-turn motif in the riboswitch hairpin. However, the positioning of neomycin in the binding site occurs at different RNA-neomycin distances for each mutant, which may explain their different regulatory activities. The subsequent induced fit arises from the interactions of the neomycin's N3 amino group with RNA, causing the G9 backbone to rearrange. In the A17G mutant, the critical C6-A17/G17 stacking forms at a closer RNA-neomycin distance compared to N1. These findings together with estimated binding free energies coincide with experiments and elucidate why the A17G mutation decreases and U15A enhances N1 activity in response to neomycin.


Assuntos
Neomicina , Riboswitch , Neomicina/metabolismo , Neomicina/farmacologia , Simulação de Dinâmica Molecular , Riboswitch/genética , Mutação , Conformação Molecular , Conformação de Ácido Nucleico , Ligantes
11.
J Pharm Bioallied Sci ; 16(Suppl 1): S143-S145, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38595628

RESUMO

Introduction: Using three-dimensional printed duplicates of the donor teeth, three-dimensional auto-transplantation is a medical procedure that moves a tooth from one location inside a patient to another. The intraoperative practicability during 3D auto-transplantation of teeth was evaluated in the present study. Material and Methods: A prospective multicenter clinical study was done among the subjects. "Preoperative cone-beam computed tomography imaging," "computer-assisted design (CAD)," and "computer-assisted manufacturing (CAM)" were used in all operations to make a 3D duplicate of the donor teeth. The clinical parameters that were evaluated were the time required for the fit, number of attempts to fit, and intra-operative experience. Results: Canines, premolars, molars, and one extra tooth were all transplanted during the 200 auto-transplantation surgeries among 152 subjects. An initial satisfactory fit of the donor tooth and an extra-alveolar time of less than one minute were achieved in 80% of the surgeries. The extra-alveolar time exceeded 3 minutes in ten teeth. Difficulties that were faced were related to the imaging, patient cooperation, and the bone quality. Conclusions: The application of the duplicate teeth by 3D printing of a donor tooth all through auto-transplantation techniques reduced the time the tooth stays extra-alveolar as well as the efforts at transplant fitting during implantation. This allowed for more challenging surgeries as well as a speedy and reliable therapy.

12.
Sensors (Basel) ; 24(7)2024 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-38610527

RESUMO

Electrothermal piezoresistive resonant cantilever sensors have been fabricated with embedded actuating (heating resistor) and sensing (piezo resistors) parts, with the latter configured in a Wheatstone bridge circuit. Due to the close spacing between these two elements, a direct thermal parasitic effect on the resonant sensor during the actuating-sensing process leads to asymmetric amplitude and reversing phase spectral responses. Such a condition affects the precise determination of the cantilever's resonant frequency, f0. Moreover, in the context of phase-locked loop-based (PLL) resonance tracking, a reversing phase spectral response hinders the resonance locking due to its ambiguity. In this work, a replica of the baseline spectral was applied to remove the thermal parasitic effect on the resonance spectra of the cantilever sensor, and its capability was simulated through mathematical analysis. This replica spectral was subtracted from the parasitized spectral using a particular calculation, resulting in optimized spectral responses. An assessment using cigarette smoke particles performed a desired spectral shifting into symmetrical amplitude shapes and monotonic phase transitions, subsequently allowing for real-time PLL-based frequency tracking.

13.
Aesthetic Plast Surg ; 48(16): 3170-3179, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38519573

RESUMO

BACKGROUND: This in vitro study compared the stability of different fixation method combinations for the zygomatic complex after simulated L-shaped osteotomy reduction malarplasty, a common facial contouring surgery in East Asia with high postoperative complications due to poor fixation methods. MATERIALS AND METHODS: The study used 108 zygoma replicas with various fixation methods combinations in the zygomatic body (L-shaped plate with short wing on zygoma and on the maxilla, two bicortical screws, one bicortical screw with L-shaped plate, square plate, and rectangular plate) and zygomatic arch (Mortise-Tenon structure, 3-hole plate, and Mortise-Tenon structure plus short screw). The failure force under incremental load was applied through the Instron tensile machine to a well-stabilized model using a rubber band simulating the masseter muscle and recorded the increasing force digitally. ANOVA test was used for comparison between recorded values (P < 0.05). RESULTS: The results showed that the most stable combination was a six-hole rectangular plate and a Mortise-Tenon structure plus one short screw (358.55 ± 51.64 N/mm2). The results also indicated that the placement vector of the fixation methods around the L-shaped osteotomy and the use of the two-bridge fixation method were important factors in enhancing the stability of the zygomatic complex. CONCLUSION: The study suggested that surgeons should choose appropriate fixation methods based on these factors to reduce postoperative complications and improve surgical outcomes. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


Assuntos
Placas Ósseas , Osteotomia , Zigoma , Humanos , Zigoma/cirurgia , Osteotomia/métodos , Fenômenos Biomecânicos , Técnicas In Vitro , Parafusos Ósseos , Procedimentos de Cirurgia Plástica/métodos
14.
Entropy (Basel) ; 26(3)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38539753

RESUMO

On approaching the dynamical transition temperature, supercooled liquids show heterogeneity over space and time. Static replica theory investigates the dynamical crossover in terms of the free energy landscape (FEL). Two kinds of static approaches have provided a self-consistent equation for determining this crossover, similar to the mode coupling theory for glassy dynamics. One uses the Morita-Hiroike formalism of the liquid state theory, whereas the other relies on the density functional theory (DFT). Each of the two approaches has advantages in terms of perturbative field theory. Here, we develop a replica field theory that has the benefits from both formulations. We introduce the generalized Franz-Parisi potential to formulate a correlation functional. Considering fluctuations around an inhomogeneous density determined by the Ramakrishnan-Yussouf DFT, we find a new closure as the stability condition of the correlation functional. The closure leads to the self-consistent equation involving the triplet direct correlation function. The present field theory further helps us study the FEL beyond the mean-field approximation.

15.
Micromachines (Basel) ; 15(3)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38542664

RESUMO

Nanopatterned tribocharge can be generated on the surface of elastomers through their replica molding with nanotextured molds. Despite its vast application potential, the physical conditions enabling the phenomenon have not been clarified in the framework of analytical mechanics. Here, we explain the final tribocharge pattern by separately applying two models, namely cohesive zone failure and cumulative fracture energy, as a function of the mold nanotexture's aspect ratio. These models deepen our understanding of the triboelectrification phenomenon.

16.
Proc Natl Acad Sci U S A ; 121(7): e2318731121, 2024 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-38315841

RESUMO

Capturing rare yet pivotal events poses a significant challenge for molecular simulations. Path sampling provides a unique approach to tackle this issue without altering the potential energy landscape or dynamics, enabling recovery of both thermodynamic and kinetic information. However, despite its exponential acceleration compared to standard molecular dynamics, generating numerous trajectories can still require a long time. By harnessing our recent algorithmic innovations-particularly subtrajectory moves with high acceptance, coupled with asynchronous replica exchange featuring infinite swaps-we establish a highly parallelizable and rapidly converging path sampling protocol, compatible with diverse high-performance computing architectures. We demonstrate our approach on the liquid-vapor phase transition in superheated water, the unfolding of the chignolin protein, and water dissociation. The latter, performed at the ab initio level, achieves comparable statistical accuracy within days, in contrast to a previous study requiring over a year.

17.
Biophys Chem ; 307: 107197, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38335808

RESUMO

BCL9 is a key protein in Wnt signaling pathway. It acts as a transcriptional co-activator to ß-catenin, and dysregulation in this pathway leads to tumor growth. Inhibiting such a protein-protein interaction is considered as a therapeutic challenge. The interaction between ß-catenin and BCL9 is facilitated by a 23-residue helical domain from BCL9 and a hydrophobic groove of ß-catenin. To prevent this interaction, a peptide that mimics the alpha-helical domain of BCL9 can be designed. Stapling is considered a successful strategy in the pursuit of designing such peptides in which amino acids side are stitched together using chemical moieties. Among the various types of cross-linkers, triazole is the most rapid and effective one synthesized via click reaction. However, the underlying interactions behind maintaining the secondary structure of stapled peptides remain less explored. In the current work, we employed the molecular dynamics simulation to study the conformational behavior of the experimentally synthesized single and double triazole stapled BCL9 peptide. Upon the addition of a triazole staple, there is a significant reduction in the conformational space of BCL9. The helical character of the stapled peptide increases with an increase in separation between the triazole cross-linkers. Also, we encompassed the Replica Exchange with Solute Tempering (REST2) simulation to validate the high-temperature response of the stapled peptide. From REST2, the PCA and t-SNE show the reduction in distinct cluster formation on the addition of triazole staple. Our study infers further development of these triazole-stapled BCL9 peptides into effective inhibitors to target the interaction between ß-catenin and BCL9.


Assuntos
Triazóis , beta Catenina , beta Catenina/química , beta Catenina/metabolismo , Triazóis/farmacologia , Proteínas de Neoplasias/química , Proteínas de Neoplasias/metabolismo , Fatores de Transcrição/metabolismo , Peptídeos/química , Estrutura Secundária de Proteína
18.
J Mol Model ; 30(3): 61, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38321243

RESUMO

CONTEXT: Amyloid fibrils are self-assembled fibrous protein aggregates that are associated with several presently incurable diseases such as Alzheimer's. disease that is characterized by the accumulation of amyloid fibrils in the brain, which leads to the formation of plaques and the death of brain cells. Disaggregation of amyloid fibrils is considered a promising approach to cure Alzheimer's disease. The mechanism of amyloid fibril formation is complex and not fully understood, making it difficult to develop drugs that can target the process. Diacetonamine and cystathionine are potential lead compounds to induce disaggregation of amyloid fibrils. METHODS: In the current research, we have used long timescale molecular simulation studies and replica exchange molecular dynamics (REMD) for 1000 ns (1 µs) to examine the mechanisms by which natural metabolites can disaggregate amyloid-beta fibrils. Molecular docking was carried out using Glide and with prior protein minimization and ligand preparation. We focused on a screening a database of natural metabolites, as potential candidates for disaggregating amyloid fibrils. We used Desmond with OPLS 3e as a force field. MM-GBSA calculations were performed. Blood-brain barrier permeability, SASA, and radius of gyration parameters were calculated.


Assuntos
Doença de Alzheimer , Amiloide , Humanos , Amiloide/metabolismo , Simulação de Dinâmica Molecular , Simulação de Acoplamento Molecular , Peptídeos beta-Amiloides/metabolismo , Doença de Alzheimer/metabolismo
19.
Int J Mol Sci ; 25(3)2024 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-38338914

RESUMO

Alzheimer's disease and Type 2 diabetes are two epidemiologically linked diseases which are closely associated with the misfolding and aggregation of amyloid proteins amyloid-ß (Aß) and human islet amyloid polypeptide (hIAPP), respectively. The co-aggregation of the two amyloid proteins is regarded as the fundamental molecular mechanism underlying their pathological association. The green tea extract epigallocatechin-3-gallate (EGCG) has been extensively demonstrated to inhibit the amyloid aggregation of Aß and hIAPP proteins. However, its potential role in amyloid co-aggregation has not been thoroughly investigated. In this study, we employed the enhanced-sampling replica exchange molecular dynamics simulation (REMD) method to investigate the effect of EGCG on the co-aggregation of Aß and hIAPP. We found that EGCG molecules substantially diminish the ß-sheet structures within the amyloid core regions of Aß and hIAPP in their co-aggregates. Through hydrogen-bond, π-π and cation-π interactions targeting polar and aromatic residues of Aß and hIAPP, EGCG effectively attenuates both inter-chain and intra-chain interactions within the co-aggregates. All these findings indicated that EGCG can effectively inhibit the co-aggregation of Aß and hIAPP. Our study expands the potential applications of EGCG as an anti-amyloidosis agent and provides therapeutic options for the pathological association of amyloid misfolding disorders.


Assuntos
Catequina/análogos & derivados , Diabetes Mellitus Tipo 2 , Polipeptídeo Amiloide das Ilhotas Pancreáticas , Humanos , Polipeptídeo Amiloide das Ilhotas Pancreáticas/química , Diabetes Mellitus Tipo 2/metabolismo , Simulação de Dinâmica Molecular , Peptídeos beta-Amiloides/metabolismo , Proteínas Amiloidogênicas/uso terapêutico , Amiloide/metabolismo
20.
Bioengineering (Basel) ; 11(1)2024 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-38247957

RESUMO

The growing interest in advancing microfluidic devices for manipulating fluids within micrometer-scale channels has prompted a shift in manufacturing practices, moving from single-component production to medium-size batches. This transition arises due to the impracticality of lab-scale manufacturing methods in accommodating the increased demand. This experimental study focuses on the design of master benchmarks 1-5, taking into consideration critical parameters such as rib width, height, and the relative width-to-height ratio. Notably, benchmarks 4 and 5 featured ribs that were strategically connected to the inlet, outlet, and reaction chamber of the master, enhancing their utility for subsequent replica production. Vat photopolymerization was employed for the fabrication of benchmarks 1-5, while replicas of benchmarks 4 and 5 were generated through polydimethylsiloxane casting. Dimensional investigations of the ribs and channels in both the master benchmarks and replicas were conducted using an optical technique validated through readability analysis based on the Michelson global contrast index. The primary goal was to evaluate the potential applicability of vat photopolymerization technology for efficiently producing microfluidic devices through a streamlined production process. Results indicate that the combination of vat photopolymerization followed by replication is well suited for achieving a minimum rib size of 25 µm in width and an aspect ratio of 1:12 for the master benchmark.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA