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INTRODUCTION: The efficacy of root canal treatment is greatly impacted by a thorough understanding of root canal anatomy. This systematic review and meta-analysis aim to thoroughly investigate the root morphology and canal configuration (RMCC) of permanent premolars (PMs). METHODOLOGY: A comprehensive analysis was conducted following the PRISMA guidelines. Literature exploration was carried out across four electronic databases (PubMed, Embase, Cochrane, and Web of Science). The risk of bias assessment was conducted for the included studies utilizing the Anatomical Quality Assessment (AQUA) tool. Data analysis was performed utilizing SPSS and RevMAN5.3.3. The meta-analysis was applied with a 95% confidence interval to calculate odds ratios (OR). RESULTS: Among the 82 selected studies, 59 studies exhibited potential bias in domain one (objective(s) and subject characteristics), followed by domain three (methodology characterization). The majority of maxillary PM1s had either single root (46.7%) or double roots (51.9%), while three-rooted variants were uncommon (1.4%). Conversely, most other PMs exhibited a single root. In terms of canal configuration, maxillary PM1s predominantly featured double distinct canals (87.2%), with the majority of maxillary PM2s displaying either a single canal (51.4%) or double canals (48.3%). Mandibular PMs were primarily characterized by single canals, accounting for 78.3% of mandibular PM1s and 90.3% of mandibular PM2s. Subgroup analyses revealed higher incidences of single-rooted and single-canalled PMs among Asians compared to Caucasians. Additionally, women exhibited a higher incidence of single-rooted PMs, while men showed a greater frequency of double-rooted PMs. CONCLUSIONS: The comprehensive analysis indicated that maxillary PM1s predominantly possess double roots and double canals, whereas maxillary PM2s and mandibular PMs were primarily characterized by single-rooted with a single canal. Notably, single root and single canal were more prevalent among women and Asian samples.
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Diente Premolar , Tomografía Computarizada de Haz Cónico , Cavidad Pulpar , Raíz del Diente , Humanos , Tomografía Computarizada de Haz Cónico/métodos , Diente Premolar/diagnóstico por imagen , Diente Premolar/anatomía & histología , Raíz del Diente/diagnóstico por imagen , Raíz del Diente/anatomía & histología , Cavidad Pulpar/diagnóstico por imagen , Cavidad Pulpar/anatomía & histologíaRESUMEN
This study presents the fabrication and evaluation of a sinusoidal extended depth-of-focus (EDoF) intraocular lens (IOL) based on our previously proposed design approach. The power, through-focus MTF, and surface profile were measured using commercial instruments. Through-focus images of a United States Air Force (USAF) 1951 resolution target formed by the fabricated IOL were compared with Symfony and AR40E under monochromatic and polychromatic light using optical bench testing. Simulations assessed visual acuity (VA) of a pseudophakic model eye with the EDoF IOL, including evaluation of tilt and decentration effects. Results indicate that the base power, add power, and the through-focus MTF@50 lp/mm of the fabricated IOL at a 3 mm pupil size align with the design specifications. The extended-depth-of-focus and imaging performance for the far vision of the fabricated IOL under both monochromatic and polychromatic light conditions at a 3.0 mm pupil diameter is comparable to that of Symfony. In addition, the fabricated IOL exhibits a similar extended-depth-of-focus for three discrete wavelengths. The pseudophakic model eye with the designed EDoF IOL demonstrates a VA exceeding 0.1 logMAR within a defocus range of 2.44 D. The VA is tolerant to both IOL tilt and decentration. These findings demonstrate the promising potential of the sinusoidal EDoF IOL design for future applications in cataract surgery.
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The onerous health and economic burden associated with head and neck squamous cell carcinoma (HNSCC) is a global predicament. Despite the advent of novel surgical techniques and therapeutic protocols, there is an incessant need for efficacious diagnostic and therapeutic targets to monitor the invasion, metastasis and recurrence of HNSCC due to its substantial morbidity and mortality. The differential expression patterns of histone deacetylases (HDACs), a group of enzymes responsible for modifying histones and regulating gene expression, have been demonstrated in neoplastic tissues. However, there is limited knowledge regarding the role of HDACs in HNSCC. Consequently, this review aims to summarize the existing research findings and explore the potential association between HDACs and HNSCC, offering fresh perspectives on therapeutic approaches targeting HDACs that could potentially enhance the efficacy of HNSCC treatment. Additionally, the Cancer Genome Atlas (TCGA) dataset, CPTAC, HPA, OmicShare, GeneMANIA and STRING databases are utilized to provide supplementary evidence on the differential expression of HDACs, their prognostic significance and predicting functions in HNSCC patients.
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Neoplasias de Cabeza y Cuello , Inhibidores de Histona Desacetilasas , Histona Desacetilasas , Carcinoma de Células Escamosas de Cabeza y Cuello , Humanos , Histona Desacetilasas/metabolismo , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello/genética , Carcinoma de Células Escamosas de Cabeza y Cuello/enzimología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/genética , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/enzimología , Inhibidores de Histona Desacetilasas/uso terapéutico , Inhibidores de Histona Desacetilasas/farmacología , Terapia Molecular Dirigida , Regulación Neoplásica de la Expresión GénicaRESUMEN
White adipose tissue browning can promote lipid burning to increase energy expenditure and improve adiposity. Here, we show that Slc35d3 expression is significantly lower in adipose tissues of obese mice. While adipocyte-specific Slc35d3 knockin is protected against diet-induced obesity, adipocyte-specific Slc35d3 knockout inhibits white adipose tissue browning and causes decreased energy expenditure and impaired insulin sensitivity in mice. Mechanistically, we confirm that SLC35D3 interacts with the NOTCH1 extracellular domain, which leads to the accumulation of NOTCH1 in the endoplasmic reticulum and thus inhibits the NOTCH1 signaling pathway. In addition, knockdown of Notch1 in mouse inguinal white adipose tissue mediated by orthotopic injection of AAV8-adiponectin-shNotch1 shows considerable improvement in obesity and glucolipid metabolism, which is more pronounced in adipocyte-specific Slc35d3 knockout mice than in knockin mice. Overall, in this study, we reveal that SLC35D3 is involved in obesity via NOTCH1 signaling, and low adipose SLC35D3 expression in obesity might be a therapeutic target for obesity and associated metabolic disorders.
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Tejido Adiposo Pardo , Tejido Adiposo Blanco , Obesidad , Receptores Notch , Animales , Ratones , Adipocitos/metabolismo , Tejido Adiposo Pardo/metabolismo , Tejido Adiposo Blanco/metabolismo , Dieta Alta en Grasa , Metabolismo Energético , Ratones Endogámicos C57BL , Ratones Noqueados , Obesidad/metabolismo , Transducción de Señal , Receptores Notch/metabolismoRESUMEN
Insulin resistance is associated with many pathological conditions, and an in-depth understanding of the mechanisms involved is necessary to improve insulin sensitivity. Here, we show that ZFYVE28 expression is decreased in insulin-sensitive obese individuals but increased in insulin-resistant individuals. Insulin signaling inhibits ZFYVE28 expression by inhibiting NOTCH1 via the RAS/ERK pathway, whereas ZFYVE28 expression is elevated due to impaired insulin signaling in insulin resistance. While Zfyve28 overexpression impairs insulin sensitivity and causes lipid accumulation, Zfyve28 knockout in mice can significantly improve insulin sensitivity and other indicators associated with insulin resistance. Mechanistically, ZFYVE28 colocalizes with early endosomes via the FYVE domain, which inhibits the generation of recycling endosomes but promotes the conversion of early to late endosomes, ultimately promoting phosphorylated insulin receptor degradation. This effect disappears with deletion of the FYVE domain. Overall, in this study, we reveal that ZFYVE28 is involved in insulin resistance by promoting phosphorylated insulin receptor degradation, and ZFYVE28 may be a potential therapeutic target to improve insulin sensitivity.
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Endosomas , Resistencia a la Insulina , Insulina , Receptor de Insulina , Animales , Ratones , Proteínas Portadoras/metabolismo , Endosomas/metabolismo , Insulina/metabolismo , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Transducción de Señal , Humanos , ObesidadRESUMEN
Nanoplastics are emerging pollutants that pose a potential threat to the environment and organisms and are widely distributed in environmental samples and food chains. The accumulation of polystyrene nanoplastics (PS-NPs) in an organism can cause oxidative stress. Currently, toxicity studies of PS-NPs mainly focus on the individual and cellular levels, whereas few studies have been conducted on the molecular mechanisms of the interaction between PS-NPs and catalase (CAT). Based on this, CAT was chosen as the target receptor for molecular toxicity research to reveal the interaction mechanism at the molecular level between PS-NPs and CAT by using various spectroscopic means and enzyme activity detection methods. The results indicated that PS-NPs destroyed the secondary structure of CAT, causing its protein skeleton to loosen and unfold, increasing the content of α-helices, decreasing the content of ß-sheets, and exposing the position of the heme group. After exposure to PS-NPs, the internal fluorophore of CAT underwent fluorescence sensitization, resulting in a micelle-like structure, which enhanced the hydrophobicity of aromatic amino acids but did not change their polarity. In addition, the aggregation state of CAT was altered upon binding to PS-NPs, and the volume was further increased. Finally, these structural changes led to a gradual decrease in CAT activity. This study presents a comprehensive assessment of the toxicity of PS-NPs at the molecular level, which can provide more experimental support for the study of the biotoxicological efficacy of PS-NPs.
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Nanopartículas , Contaminantes Químicos del Agua , Poliestirenos/toxicidad , Poliestirenos/química , Microplásticos , Catalasa , Estrés Oxidativo , Nanopartículas/química , Contaminantes Químicos del Agua/toxicidadRESUMEN
Microplastics (MPs) can affect phytoplankton and its photosynthetic performance in many but often in negative ways. Phytoplankton is an important source of dissolved organic matter (DOM) in aquatic ecosystems, but the impact of MPs on the algal production of DOM is poorly known. We investigated the impacts of polyvinyl chloride MPs on the growth and DOM production by Chlamydomonas reinhardtii microalgae in a 28-day-long experiment. During the exponential growth phase of C. reinhardtii, MPs slightly affected algal growth and DOM production. At the end of experiment, MPs decreased the biomass of C. reinhardtii by 43 % in the treatment with MPs exposed to simulated solar radiation prior the experiment (light-aged) and more than in the treatment with virgin MPs. The light-aged MPs decreased algal DOM production by 38 % and modified the chemical composition of DOM. According to spectroscopic analyses, the light-aged MPs increased aromaticity, average molecular weight and fluorescence of DOM produced by C. reinhardtii. The elevated fluorescence was associated with humic-like components identified by a 5-component parallel factor analysis (PARAFAC) from the excitation-emission matrices. We conclude that although MPs can leach DOM to aquatic ecosystems, they potentially modify the aquatic DOM more by interfering with the algal production of DOM and changing the composition of produced DOM.
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Microalgas , Plásticos , Microplásticos , Materia Orgánica Disuelta , Ecosistema , Fitoplancton , Espectrometría de Fluorescencia/métodos , Sustancias Húmicas/análisis , Análisis FactorialRESUMEN
Microplastics (MPs) undergo physical, chemical, and biological aging in the environment, leading to changes in their physicochemical properties, affecting migration characteristics and toxicity. Oxidative stress effects induced by MPs in vivo have been extensively studied, but the toxicity difference between virgin and aged MPs and the interactions between antioxidant enzymes and MPs in vitro have not been reported yet. This study investigated the structural and functional changes of catalase (CAT) induced by virgin and aged PVC-MPs. It was shown that light irradiation aged the PVC-MPs, and the aging mechanism was photooxidation, resulting in a rough surface and appearing holes and pits. Because of the changes in physicochemical properties, aged MPs had more binding sites than virgin MPs. Fluorescence and synchronous fluorescence spectra results suggested that MPs quenched the endogenous fluorescence of CAT and interacted with tryptophane and tyrosine residues. The virgin MPs had no significant effect on the skeleton of CAT, while the skeleton and the polypeptide chains of CAT became loosened and unfolded after binding with the aged MPs. Moreover, the interactions of CAT with virgin/aged MPs increased the α-helix and decreased the ß-sheet contents, destroyed the solvent shell, and resulted in a dispersion of CAT. Due to the large size, MPs cannot enter the interior of CAT and have no effects on the heme groups and activity of CAT. The interaction mechanism between MPs and CAT may be that MPs adsorb CAT to form the protein corona, and aged MPs had more binding sites. This study is the first comprehensive investigation of the effect of aging on the interaction between MPs and biomacromolecules and highlights the potential negative effects of MPs on antioxidant enzymes.
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Microplásticos , Contaminantes Químicos del Agua , Microplásticos/toxicidad , Plásticos , Catalasa , Antioxidantes , Estrés Oxidativo , Contaminantes Químicos del Agua/toxicidad , Contaminantes Químicos del Agua/análisisRESUMEN
Microplastics are harmful pollutants that widely exist worldwide and pose a severe threat to all types of organisms. The effects of polystyrene microplastics (PS-MPs) on organisms have been extensively studied, but the interaction mechanism between PS-MPs and superoxide dismutase (SOD) at the molecular level has not been reported yet. Therefore, based on multiple spectroscopic methods and enzyme activity measurements, the molecular mechanism of the interaction between PS-MPs and SOD was investigated. The multispectral results showed that the protein skeleton and secondary structure of SOD were altered by PS-MPs, resulting in decreased α-helix and ß-sheet content. After PS-MPs exposure, fluorescence sensitization occurred, and micelles were formed, along with the enhanced hydrophobicity of aromatic amino acids in SOD. Moreover, the resonance light scattering (RLS) spectra result suggested that the PS-MPs and SOD combined to form a larger complex. Eventually, the activity of SOD was increased due to these structural changes, and the concentration of PS-MPs is positively correlated with SOD activity. This study can provide experimental support for studying the toxicological effects of PS-MPs.
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Poliestirenos , Contaminantes Químicos del Agua , Poliestirenos/metabolismo , Microplásticos , Plásticos , Superóxido Dismutasa , Contaminantes Químicos del Agua/metabolismo , Análisis EspectralRESUMEN
The preparation of the wavelength-scale micropores on metallic surfaces is limited by the high opacity of metal. At present, most micropores reported in the literature are more than 20 µm in diameter, which is not only large in size, but renders them inefficient for processing so that it is difficult to meet the needs of some special fields, such as aerospace, biotechnology, and so on. In this paper, the rapid laser fabrications of the wavelength-scale micropores on various metallic surfaces are achieved through femtosecond MHz burst Bessel beam ablation. Taking advantage of the long-depth focal field of the Bessel beam, high-density micropores with a diameter of 1.3 µm and a depth of 10.5 µm are prepared on metal by MHz burst accumulation; in addition, the rapid fabrication of 2000 micropores can be achieved in 1 s. The guidelines and experimental results illustrate that the formations of the wavelength-scale porous structures are the result of the co-action of the laser-induced periodic surface structure (LIPSS) effect and Bessel beam interference. Porous metal can be used to store lubricant and form a lubricating layer on the metallic surface, thus endowing the metal resistance to various liquids' adhesion. The microporous formation process on metal provides a new physical insight for the rapid preparation of wavelength-scale metallic micropores, and promotes the application of porous metal in the fields of catalysis, gas adsorption, structural templates, and bio-transportation fields.
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The widespread use of antibiotics leads to the increasing drug resistance of bacteria and poses a threat to human health. Therefore, there is an urgent need to develop new antibacterial strategies. Herein, based on the good photothermal properties of Copper sulfide (CuS) nanoparticles under near infrared (NIR) laser, we developed a NIR-â ¡ window triple-mode synergetic antibacterial cCuS (cationic CuS) @Vancomycin (Van) nanoplatform. In the proposed nanoplatform, the positive charge on the surface makes cCuS@Van nanoplatform show better bacterial uptake and membrane damage; vancomycin induces chemical sterilization and provides a targeting effect to the nanoplatform; combined with the strong photothermal effect and deep tissue penetration at the excitation of 1064 nm laser, cCuS@Van nanoplatform can effectively kill bacterial. The photothermal conversion efficiency of the nanoplatform can reach 49.12 % and in vitro experiments show a sterilizing rate of more than 99.5 % to staphylococcus aureus (S. aureus) at the concentration of 3.0 µM, which also demonstrated the synergistic effect of cCuS@Van nanoplatform. In addition, low cytotoxicity to human cells conforms the good biocompatibility of the as-prepared cCuS@Van nanoplatform, which endows it a good application prospect in the field of antibacterial, such as wound healing and implant sterilization.
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Nanopartículas , Vancomicina , Humanos , Antibacterianos/farmacología , Antibacterianos/química , Bacterias , Cobre/farmacología , Cobre/química , Nanopartículas/química , Staphylococcus aureus , Sulfuros/farmacología , Sulfuros/química , Vancomicina/farmacología , Vancomicina/química , Espectroscopía Infrarroja CortaRESUMEN
With the rapid development of social economy and Internet of Things, the society has entered the era of networking, digitalization, and intelligence, bringing great convenience to people's life; Internet of Things music system also has begun to get people's extensive attention. Due to the influence of such factors as strong music professionalism, complex music theory knowledge, and diverse changes, it is difficult to identify music features. In order to strengthen the user's personal experience of the music system, the multimusic systems are interconnected through information technology to realize the connection between objects and people. The system uses an embedded processor to realize the central control module and then according to network standard the sensor network is built, through radio frequency identification (RFID) technology for light, sound, infrared sensor, temperature, and other sensors for information reading. Music selection logic is designed based on the theory of music psychology and user behavior log, so as to select the best music for users to improve their mood and improve their life quality and work and study efficiency. At the same time, the system uses voice recognition technology to enhance user interaction, through the system, to provide the website to share their own music data and comments on songs and view song information, and the system runs stably and can collect high quality music signals and correctly identify the characteristics of music form and emotional characteristics.
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Internet de las Cosas , Música , Humanos , Internet , Reconocimiento en Psicología , TecnologíaRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Senegenin (SEN), an active compound extracted from the traditional Chinese herb Polygala tenuifolia Willd. (a species in the genus Polygala, family Polygalaceae), could nourish neurons and resist neuronal damage in mouse models of Alzheimer's disease (AD). Amyloid-ß (Aß) depositions in neuronal cells may cause pathological changes such as oxidative stress which one return could cause severe damage to mitochondria in AD patients or animal models. Mitophagy is an important mechanism to selectively remove damaged mitochondria. In neurons, this process is mainly mediated by PTEN-induced putative kinase 1 (PINK1)/Parkin pathway. Previous studies have shown that SEN could reduce mitochondrial damage and inhibit apoptosis in neurons. Therefore, this study speculated that SEN might activate mitophagy to clear damaged mitochondria, thereby mitigating Aß-induced cell damage in neuronal cells. AIM OF THE STUDY: This study aimed to determine the effects of SEN on Aß-induced cell damage, and further to explore whether SEN could induce mitophagy. Moreover, the regulatory role of mitophagy in the neuroptrotective effect of SEN would be elucidated. MATERIALS AND METHODS: This study established an in vitro cell damage model using Aß1-42 to treat mouse hippocampal neuron HT22 cells. The effects of SEN on cell damage were determined by MTT assay and lactate dehydrogenase (LDH) release assay. Reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by Cytation™5 cell imaging microplate detection system. The apoptotic rate was analyzed by flow cytometry. The effects of SEN on mitophagy were detected by transmission electron microscope, immunofluorescence and immunoblotting. RESULTS: Firstly, HT22 cells were treated with 30 µM Aß1-42 for 24 h to establish the damage model. It was found that 30 µM Aß1-42 caused neuronal damages as evidenced by reduced cell viability, increased LDH release and ROS, collapsed MMP and elevated apoptosis. Secondly, Aß1-42-incubated cells were treated with 10, 20, 40 and 60 µM SEN for 24 h. SEN significantly reduced the damage of Aß1-42-incubated cells as shown by recovered cell viability and MMP, reduced apoptosis and ROS. Notably, SEN induced the formation of mitophagosomes and mitolysosomes, and elevated the conversion of LC3 I to LC3 II. Moreover, SEN down-regulated the expression of p62, promoted the accumulation of full-length PINK1 and the translocation of Parkin to mitochondria, decreased the expression of mitochondrial matrix protein HSP60, thus activating the PINK1/Parkin-mediated mitophagy. However, when cells were pretreated with 5 µM CsA (Cyclosporine A, a mitophagy inhibitor) for 2 h and then co-treated with 20 and 40 µM SEN for 24 h, the protective effects of SEN were compromised. CONCLUSIONS: The present study demonstrated that SEN could alleviate Aß1-42-induced cell damage through PINK1/Parkin-mediated mitophagy. Our findings justify the traditional use of P. tenuifolia in China with anti-aging or anti-neurodegenerative effects.
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Mitofagia , Proteínas Quinasas , Animales , Humanos , Ratones , Péptidos beta-Amiloides , Medicamentos Herbarios Chinos , Fragmentos de Péptidos , Proteínas Quinasas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Ubiquitina-Proteína Ligasas/metabolismoRESUMEN
BACKGROUND: Sodium dehydroacetate (DHA-S) is a common food additive, which can combine with serum proteins in the plasma, but the interaction mechanism between DHA-S and human serum albumin (HSA) is unclear. In this study, multiple spectroscopy techniques, isothermal titration calorimetry (ITC), molecular docking and esterase activity test were employed to investigate the interaction mechanism of DHA-S and HSA. RESULTS: A DHA-S-HSA complex was formed and the structure of HSA were altered by DHA-S. Since DHA-S changed the tight structure of the hydrophobic subdomain IIA where tryptophan (Trp) was placed, the hydrophobicity of the microenvironment of HSA was enhanced. With the addition of DHA-S, the skeleton structure of HSA became loose and the solvent shell on the HSA surface was destroyed. DHA-S altered the secondary structure of HSA, resulting in the decreased α-helix and increased ß-sheet contents. The interaction was exothermic and spontaneous driven by van der Waals and hydrogen bonding. DHA-S inhibited the esterase activity of HSA. Molecular docking demonstrated that the binding site of DHA-S on HSA located at the cavity of subdomains IIA and IIIA, but the amino acids related to esterase activity of HSA were not in the binding pocket, indicating that the mechanism by which DHA-S inhibited HSA esterase activity was the change in protein structure. CONCLUSION: This study illustrated that DHA-S interacted with HSA and the structure and function of HSA were affected by DHA-S. This research could help to understand the toxicity of DHA-S and provide basic data for safe use of food additives. © 2021 Society of Chemical Industry.
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Esterasas , Albúmina Sérica Humana , Sitios de Unión , Dicroismo Circular , Esterasas/metabolismo , Humanos , Enlace de Hidrógeno , Simulación del Acoplamiento Molecular , Unión Proteica , Pironas , Albúmina Sérica Humana/química , Albúmina Sérica Humana/metabolismo , Espectrometría de Fluorescencia , TermodinámicaRESUMEN
In this paper, we mainly study the interaction mechanism between food additives and antioxidant enzymes. Spectral methods were used to study the effect of sodium benzoate on the structure and function of lysozyme at the molecular level. Multi-spectroscopic results showed that sodium benzoate statically quenched the intrinsic fluorescence of lysozyme, formed complexes with lysozyme, increased the polarity of the aromatic amino acid, effected the molecular skeleton of lysozyme and stretched the secondary structure. The molecular docking and isothermal titration calorimetry (ITC) results showed that sodium benzoate entered the depression of the surface of lysozyme molecule both through hydrophobic interaction and hydrogen bond. Sodium benzoate was linked to tryptophan (Trp-63) by a hydrogen bond with a bond length of 2.48 Å. Thermodynamic studies showed that the combination was spontaneous, as the values of the enthalpy change (ΔH) and the entropy change (ΔS) were calculated to be 12.558 kJmol-1 and 25 kJmol-1k-1, respectively. Enzyme activity determination showed that Sodium benzoate increased lysozyme activity by 22.31%. This study can provide experimental support for evaluating the edible safety of sodium benzoate.
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Simulación del Acoplamiento Molecular , Sitios de Unión , Calorimetría , Unión Proteica , Espectrometría de Fluorescencia , Análisis Espectral , TermodinámicaRESUMEN
Due to the rapid development of industrial society, air pollution is becoming a serious problem which has being a huge threat to human health. Ultrafine particles (UFPs), one of the major air pollutants, are often the culprits of human diseases. At present, most of the toxicological studies of UFPs focus on their biological effects on lung cells and tissues, but there are less researches taking aim at the negative effects on functional proteins within the body. Therefore, we experimentally explored the effects of ultrafine carbon black (UFCB) on the structure and function of trypsin. After a short-term exposure to UFCB, the trypsin aromatic amino acid microenvironment, protein backbone and secondary structure were changed significantly, and the enzyme activity showed a trend that rose at first, then dropped. In addition, UFCB interacts with trypsin in the form of a complex. These studies demonstrated the negative effects of UFCB on trypsin, evidencing potential effects on animals and humans.
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Material Particulado/toxicidad , Hollín/toxicidad , Tripsina/química , Tripsina/metabolismo , Animales , Bovinos , Dicroismo Circular , Regulación de la Expresión Génica/efectos de los fármacos , Modelos Moleculares , Tamaño de la Partícula , Estructura Secundaria de Proteína/efectos de los fármacos , Análisis Espectral , Tripsina/efectos de los fármacosRESUMEN
Purpose: The spatial distribution of collagen fibril dispersion has a significant impact on both corneal biomechanical and optical behaviors. The goal of this study was to demonstrate a novel method to characterize collagen fibril dispersion using intraocular pressure (IOP)-induced changes in corneal optical aberrations for individualized finite-element (FE) modeling. Methods: The method was tested through both numerical simulations and ex vivo experiments. Inflation tests were simulated in FE models with three assumed patterns of collagen fibril dispersion and experimentally on three rhesus monkey corneas. Geometry, matrix stiffness, and the IOP-induced changes in wavefront aberrations were measured, and the collagen fibril dispersion was characterized. An individualized corneal model with customized collagen fibril dispersion was developed, and the estimated optical aberrations were compared with the measured data. Results: For the theoretical investigations, three assumed distributions of fibril dispersion were all successfully characterized. The estimated optical aberrations closely matched the measured data, with average root-mean-square (RMS) differences of 0.29, 0.24, and 0.10 µm for the three patterns, respectively. The overall features of the IOP-induced changes in optical aberrations were estimated for two ex vivo monkey corneas, with average RMS differences of 0.57 and 0.43 µm. Characterization of the fibril dispersion in the third cornea might have been affected by corneal hydration, resulting in an increased RMS difference, 0.8 µm. Conclusions: A more advanced corneal model with individualized distribution of collagen fibril dispersion can be developed and used to improve our ability to understand both biomechanical and optical behaviors of the cornea.
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Colágeno/fisiología , Córnea/fisiología , Animales , Fenómenos Biomecánicos , Córnea/patología , Análisis de Elementos Finitos , Presión Intraocular , Macaca mulatta , Masculino , Modems , Trastornos de la Visión/etiología , Trastornos de la Visión/patologíaRESUMEN
Long-chain perfluoroalkyl acids (PFAAs) such as perfluorodecanoic acid (PFDA) are toxic, persistent organic pollutants. This study investigated the harmful effect of PFDA on mouse primary nephrocytes and its mechanism at cellular and molecular levels. Cellular results showed that PFDA exhibited nephrotoxicity with decreased cell viability and increased apoptosis. The increase of intracellular reactive oxygen species (ROS) content and the decrease of intracellular superoxide dismutase (SOD) activity were significant (pâ¯<â¯0.01) when PFDA concentration exceeded 10⯵M. Additionally, the molecular results indicated that PFDA bind with Val-A98 in the surface of Cu/Zn-SOD by a 3.11â¯Å hydrogen bond driven by Van der Waals' force and hydrogen bonding force, which triggered the structural changes and decreased activity of Cu/Zn-SOD. Altogether, the intracellular oxidative stress is the main driver of nephrocyte apoptosis; and the interaction of PFDA and Cu/Zn-SOD exacerbated the oxidative stress in nephrocytes, which is also a nonnegligible reason of cytotoxicity induced by PDFA. This study represented a meaningful method to explore the toxic effect and mechanism of xenobiotics at cellular and molecular levels. The findings have implications for revealing the clearance of long-chain PFAAs in vivo.
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Ácidos Decanoicos/toxicidad , Contaminantes Ambientales/toxicidad , Fluorocarburos/toxicidad , Riñón/citología , Animales , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Masculino , Ratones Endogámicos C57BL , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
As typical perfluorinated compounds (PFCs), perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) have been detected in various environmental media and their toxic effects have been extensively studied. Nevertheless, it remains unclear how PFCs cause cell apoptosis in healthy hepatocytes by inducing oxidative stress at the subcellular and molecular levels. In this study, the apoptotic pathways induced by PFOA and PFOS were explored. Besides, the effects of PFCs on the structure and function of lysozyme (LYZ) were investigated. After PFOA and PFOS exposure, the cell membrane and mitochondrial membrane potential were damaged. Further, PFOA and PFOS increased intracellular Ca2+ levels to 174.41 ± 1.70 and 158.91 ± 5.94%, respectively. Ultimately, caspase-3 was activated, causing cell apoptosis. As an indirect antioxidant enzyme, the molecular structure of LYZ was destroyed after interacting with PFOA and PFOS. Both PFOA and PFOS bound to the active center of LYZ, leading to the decrease of LYZ activity to 91.26 ± 0.78 and 76.01 ± 4.86%, respectively. This study demonstrates that PFOA and PFOS inhibit LYZ function, which can reduce the body's ability to resist oxidative stress, and then lead to mitochondria-mediated apoptosis.
Asunto(s)
Ácidos Alcanesulfónicos/farmacología , Apoptosis/efectos de los fármacos , Caprilatos/farmacología , Fluorocarburos/farmacología , Hepatocitos/efectos de los fármacos , Calcio/metabolismo , Caspasa 3/metabolismo , Línea Celular , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Hepatocitos/citología , Hepatocitos/metabolismo , Humanos , Estrés Oxidativo/efectos de los fármacosRESUMEN
Whole body vibration (WBV) is a non-invasive physical therapy that has recently been included in the hospital's patient rehabilitation training catalog, but its health effects have not been sufficiently studied. In the present study, to examine the possible effects of WBV on immune cell differentiation, the IFN, IL-4,-17, F4/80 and CD3,-4,-8,-11b,-11c,-19 markers were used to characterizing the cells in mouse spleen. The results showed that the CD4 and CD25 positive lymphocytes in the spleen were significantly increased in the WBV group, and the population of Treg cells was enhanced significantly in response to WBV. Since the differentiation in immune cells is usually associated with microbiota, therefore the intestinal flora was characterized in mice and human individuals. The results indicated that WBV significantly reduced the α-diversity of mouse intestinal microbiota. Moreover, the principal coordinate analysis (PCoA) results indicated that the ß-diversities of both mice and human fecal microbiota increased after WBV. Analysis of the bacterial composition indicated that the contents of a variety of bacteria changed in mice upon the stimulation of vibration, such as Lactobacillus animalis in mice, and Lactobacillus paraplantarum and Lactobacillus sanfranciscensis in human. The succeeding correlation analysis revealed that some bacteria with significant content variations were correlated to the regulatory T cell differentiation in mice and physical characteristics in human. Our research will provide the basis for future non-invasive treatment of microbial and immune related diseases.