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1.
Cell ; 174(6): 1465-1476.e13, 2018 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-30122350

RESUMO

Cell-penetrating peptides (CPPs) are short protein segments that can transport cargos into cells. Although CPPs are widely studied as potential drug delivery tools, their role in normal cell physiology is poorly understood. Early during infection, the L2 capsid protein of human papillomaviruses binds retromer, a cytoplasmic trafficking factor required for delivery of the incoming non-enveloped virus into the retrograde transport pathway. Here, we show that the C terminus of HPV L2 proteins contains a conserved cationic CPP that drives passage of a segment of the L2 protein through the endosomal membrane into the cytoplasm, where it binds retromer, thereby sorting the virus into the retrograde pathway for transport to the trans-Golgi network. These experiments define the cell-autonomous biological role of a CPP in its natural context and reveal how a luminal viral protein engages an essential cytoplasmic entry factor.


Assuntos
Proteínas do Capsídeo/metabolismo , Peptídeos Penetradores de Células/metabolismo , Proteínas Oncogênicas Virais/metabolismo , Sequência de Aminoácidos , Proteínas do Capsídeo/química , Proteínas do Capsídeo/genética , Peptídeos Penetradores de Células/química , Peptídeos Penetradores de Células/genética , Endossomos/metabolismo , Complexo de Golgi/virologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Células HEK293 , Células HeLa , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/fisiologia , Humanos , Mutagênese , Proteínas Oncogênicas Virais/química , Proteínas Oncogênicas Virais/genética , Transporte Proteico , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Alinhamento de Sequência , Ligação Viral , Internalização do Vírus
2.
Am J Pathol ; 193(12): 2172-2181, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37741450

RESUMO

Autophagy has been proposed to play a dual role in cancer-as a tumor suppressor in early stages and oncogenic in late stages of tumorigenesis. This study investigated the role of autophagy in oral carcinogenesis using the model of oral squamous cell carcinoma (OSCC) induced by carcinogen 4-nitroquinoline 1-oxide (4NQO), mimicking molecular and histopathologic aspects of human OSCC. The induction of autophagy by spermidine (SPD) treatment reduced the severity of lesions and the incidence of OSCC in mice exposed to 4NQO. On the other hand, autophagy inhibition by chloroquine treatment had no protection. The comet assay indicated that SPD reduced 4NQO-induced DNA damage, likely related to the activation of DNA repair and the decrease of reactive oxygen species. As sphingolipid alterations have been reported in OSCC, sphingolipids in the tongue and plasma of animals were analyzed and plasma C16 ceramide levels were shown to increase proportionally to lesion severity, indicating its potential as a biomarker. Mice exposed to 4NQO plus SPD had lower levels of C16 ceramide than the 4NQO group, which indicated SPD's ability to prevent the 4NQO-induced carcinogenesis. Together, these data indicate that activation of autophagy has a tumor suppressor role during the early stages of oral carcinogenesis. Because of its ability to induce autophagy accompanied by reduced oxidative stress and DNA damage, SPD may have a protective action against chemically induced oral cancer.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Neoplasias da Língua , Humanos , Camundongos , Animais , Carcinoma de Células Escamosas/induzido quimicamente , Carcinoma de Células Escamosas/prevenção & controle , Carcinoma de Células Escamosas/genética , Neoplasias Bucais/induzido quimicamente , Neoplasias Bucais/prevenção & controle , Neoplasias Bucais/genética , Espermidina/efeitos adversos , Neoplasias da Língua/patologia , 4-Nitroquinolina-1-Óxido/toxicidade , Carcinogênese/patologia , Carcinógenos , Carcinoma de Células Escamosas de Cabeça e Pescoço , Dano ao DNA , Reparo do DNA , Estresse Oxidativo , Ceramidas
3.
J Chem Inf Model ; 64(8): 3322-3331, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38536765

RESUMO

This work reports on new software for automatic conformer energy benchmarking calculations for flexible molecules. The software workflow consists of four parts: conformational search, preoptimization, optimization, and frequency calculations at a higher level and last calculations using several theoretical levels. The software was written to be user-friendly and versatile to be used by nonexperts in computational chemistry. Any theoretical levels available in either Gaussian 16 or ORCA 5 may be applied in the benchmarking study. The workflow will automatically run conformational search calculations and deal with conformers that converge to the same minimum and those that show a negative frequency. At the end of the workflow, the user will have the mean absolute deviations and the most accurate method/DFT functional and basis set in comparison to the benchmark to be applied for the molecular system of interest. Case examples are given at the end of the paper that may help users to get insight into the software's main features.


Assuntos
Benchmarking , Software , Conformação Molecular , Automação , Elétrons , Modelos Moleculares
4.
J Toxicol Environ Health B Crit Rev ; 27(1): 1-20, 2024 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-37889647

RESUMO

Bioactive compounds derived from secondary metabolism in animals have refined selectivity and potency for certain biological targets. The superfamily Dendrobatoidea is adapted to the dietary sequestration and secretion of toxic alkaloids, which play a role in several biological activities, and thus serve as a potential source for pharmacological and biotechnological applications. This article constitutes a scoping review to understand the trends in experimental research involving bioactive alkaloids derived from Dendrobatoidea based upon scientometric approaches. Forty-eight (48) publications were found in 30 journals in the period of 60 years, between 1962 and 2022. More than 23 structural classes of alkaloids were cited, with 27.63% for batrachotoxins, 13.64% for pyridinics, with an emphasis on epibatidine, 16.36% for pumiliotoxins, and 11.82% for histrionicotoxins. These tests included in vivo (54.9%), in vitro (39.4%), and in silico simulations (5.6%). Most compounds (54.8%) were isolated from skin extracts, whereas the remainder were obtained through molecular synthesis. Thirteen main biological activities were identified, including acetylcholinesterase inhibitors (27.59%), sodium channel inhibitors (12.07%), cardiac (12.07%), analgesic (8.62%), and neuromuscular effects (8.62%). The substances were cited as being of natural origin in the "Dendrobatidae" family, genus "Phyllobates," "Dendrobates," and seven species: Epipedobates tricolor, Phyllobates aurotaenia, Oophaga histrionica, Oophaga pumilio, Phyllobates terribilis, Epipedobates anthonyi, and Ameerega flavopicta. To date, only a few biological activities have been experimentally tested; hence, further studies on the bioprospecting of animal compounds and ecological approaches are needed.


Assuntos
Alcaloides , Peçonhas , Animais , Acetilcolinesterase , Anuros/metabolismo , Batraquiotoxinas/química , Alcaloides/química , Alcaloides/metabolismo
5.
Biometals ; 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691278

RESUMO

Under normal physiological conditions, the endogenous Labile Iron Pool (LIP) constitutes a ubiquitous, dynamic, tightly regulated reservoir of cellular ferrous iron. Furthermore, LIP is loaded into new apo-iron proteins, a process akin to the activity of metallochaperones. Despite such importance on iron metabolism, the LIP identity and binding properties have remained elusive. We hypothesized that LIP binds to cell constituents (generically denoted C) and forms an iron complex termed CLIP. Combining this binding model with the established Calcein (CA) methodology for assessing cytosolic LIP, we have formulated an equation featuring two experimentally quantifiable parameters (the concentrations of the cytosolic free CA and CA and LIP complex termed CALIP) and three unknown parameters (the total concentrations of LIP and C and their thermodynamic affinity constant Kd). The fittings of cytosolic CALIP × CA concentrations data encompassing a few cellular models to this equation with floating unknown parameters were successful. The computed adjusted total LIP (LIPT) and C (CT) concentrations fall within the sub-to-low micromolar range while the computed Kd was in the 10-2 µM range for all cell types. Thus, LIP binds and has high affinity to cellular constituents found in low concentrations and has remarkably similar properties across different cell types, shedding fresh light on the properties of endogenous LIP within cells.

6.
J Phys Chem A ; 128(2): 413-419, 2024 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-38174881

RESUMO

In the gas-phase chemistry of the atmosphere and automotive fuel combustion, peroxyl radical intermediates are formed following O2 addition to carbon-centered radicals which then initiate a complex network of radical reactions that govern the oxidative processing of hydrocarbons. The rapid association of the phenyl radical-a fundamental radical related to benzene-with O2 has hitherto been modeled as a barrierless process, a common assumption for peroxyl radical formation. Here, we provide an alternate explanation for the kinetics of this reaction by deploying double-hybrid density functional theory (DFT), at the DSD-PBEP86-D3(BJ)/aug-cc-pVTZ level of theory, and locate a submerged adiabatic transition state connected to a prereaction complex along the reaction entrance pathway. Using this potential energy scheme, experimental rate coefficients k(T) for the addition of O2 to the phenyl radical are accurately reproduced within a microcanonical kinetic model. This work highlights that purportedly barrierless radical oxidation reactions may instead be modeled using stationary points, which in turn provides insight into pressure and temperature dependence.

7.
Int J Sports Med ; 2024 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-38190980

RESUMO

The objective of this meta-analysis is to compare the effects on muscle strength and hypertrophy of low and high-intensity aerobic training with BFR (LI-BFR and HI-BFR) versus low and high-intensity aerobic training without BFR (LI and HI). The search was performed in five databases, by two independent researchers, and the terms and keywords used to optimize the searches were related to blood flow restriction and aerobic training. All studies were evaluated for methodological quality using the PEDro scale and for quality of evidence using the GRADE system. Meta-analyses were conducted using RevMan software. After data extraction, 11 studies met all eligibility criteria and were included in the systematic review. The results of the overall analysis between LI-BFR vs. LI showed a significant difference in muscle strength of knee extensors; for hypertrophy, LI was superior to LI-BFR with clinical relevance. Comparing HI-BFR vs. HI there was no superiority for muscle strength. In conclusion, for strength gains very low-quality evidence was found to support no superiority between LI-BFR and HI-BFR compared to LI and HI, respectively. For muscle hypertrophy, superiority of LI was found compared to LI-BFR, with a very low level of evidence.

8.
HPB (Oxford) ; 26(1): 137-144, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37722997

RESUMO

BACKGROUND: Celiac trunk compression by the median arcuate ligament (MAL) increases the risk of ischemic complications following gastrointestinal surgical procedures. Previous studies suggest increased risk of hepatic artery thrombosis (HAT) in orthotopic liver transplant (OLT) recipients. The aim of this study is to investigate the impact of untreated MAL compression (MAL-C) on biliary complications in OLT. METHODS: Contrast-enhanced imaging was used to classify celiac trunk stenosis by MAL-C. Medical records were reviewed to extract pre-transplant, transplant and post-transplant data. Patients were divided into two groups: no MAL compression (nMAL-C) and MAL-C. The primary endpoint was biliary complications. Secondary endpoints were HAT and graft survival. RESULTS: 305 OLT were performed from 2010 to 2021, of which 219 were included for analysis: 185 (84.5%) patients without and 34 (15.5%) with MAL-C. The incidence of HAT was 5.9% in both groups. Biliary complications were more common in the MAL-C group (35.3% vs. 17.8%, p = 0.035). Graft survival was decreased in patients with MAL-C (p = 0.035). CONCLUSIONS: MAL-C of the celiac trunk was associated with increased risk of biliary complications and inferior graft survival in OLT patients. These findings highlight the importance of preoperative screening and treatment of MAL in this population.


Assuntos
Sistema Biliar , Transplante de Fígado , Trombose , Humanos , Transplante de Fígado/efeitos adversos , Transplante de Fígado/métodos , Artéria Hepática/diagnóstico por imagem , Artéria Hepática/cirurgia , Constrição Patológica/complicações , Constrição Patológica/cirurgia , Artéria Celíaca/diagnóstico por imagem , Artéria Celíaca/cirurgia , Ligamentos/diagnóstico por imagem , Ligamentos/cirurgia
9.
PLoS Comput Biol ; 18(5): e1010045, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35500014

RESUMO

Identifying structural differences among proteins can be a non-trivial task. When contrasting ensembles of protein structures obtained from molecular dynamics simulations, biologically-relevant features can be easily overshadowed by spurious fluctuations. Here, we present SINATRA Pro, a computational pipeline designed to robustly identify topological differences between two sets of protein structures. Algorithmically, SINATRA Pro works by first taking in the 3D atomic coordinates for each protein snapshot and summarizing them according to their underlying topology. Statistically significant topological features are then projected back onto a user-selected representative protein structure, thus facilitating the visual identification of biophysical signatures of different protein ensembles. We assess the ability of SINATRA Pro to detect minute conformational changes in five independent protein systems of varying complexities. In all test cases, SINATRA Pro identifies known structural features that have been validated by previous experimental and computational studies, as well as novel features that are also likely to be biologically-relevant according to the literature. These results highlight SINATRA Pro as a promising method for facilitating the non-trivial task of pattern recognition in trajectories resulting from molecular dynamics simulations, with substantially increased resolution.


Assuntos
Ciência de Dados , Simulação de Dinâmica Molecular , Biofísica , Conformação Proteica , Proteínas/química
10.
BMC Infect Dis ; 23(1): 55, 2023 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-36703115

RESUMO

BACKGROUND: Encephalitis is an inflammation of the cerebral parenchyma manifested by acute symptoms such as fever, headaches, and other neurological disorders. Its etiology is mostly viral, with herpes simplex virus being a frequent etiological agent in children. The development of neurological sequelae is a serious outcome associated with this infection. OBJECTIVE: To assess the general prevalence and types of neurological sequelae in children after a case of acute viral encephalitis caused by HSV. METHODS: This systematic review and meta-analysis was developed following the PRISMA guidelines. The literature search was carried out in the MEDLINE, Embase, SciELO, LILACS, Cochrane, CINAHL, PsycINFO, and Web of Science databases. Studies were included of children with confirmed HSV infection and that presented a description of neurological sequelae associated with that infection. For the meta-analysis of general prevalence and of the types of neurological sequelae a random effects model was used. RESULTS: Of the 2827 articles chosen in the initial search, nine studies were included in the systematic review and meta-analysis. The general prevalence of neurological sequelae was 50.7% (95% CI 39.2-62.2). The most frequent sequelae were related to mental disability, with a 42.1% prevalence (95% CI 30-55.2); on the other hand, the least frequent sequelae were those related with visual impairment, with a 5.9% prevalence (95% CI 2.2-14.6). The included studies presented regular quality and substantial heterogeneity. CONCLUSION: Even with antiviral therapy, half of patients will develop some type of disability.


Assuntos
Encefalite por Herpes Simples , Encefalite Viral , Encefalite , Herpes Simples , Humanos , Criança , Simplexvirus , Herpes Simples/complicações , Progressão da Doença , Encefalite/complicações , Encefalite por Herpes Simples/complicações
11.
Langenbecks Arch Surg ; 408(1): 26, 2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36639606

RESUMO

PURPOSE: Locoregional therapies (LRT) are employed for bridging patients with hepatocellular carcinoma (HCC) awaiting orthotopic liver transplantation (OLT). Although the main LRT options include transarterial chemoembolization (TACE) and radiofrequency ablation (RFA), percutaneous ethanol injection (PEI) is an alternative with considerably lower costs. This study is a pioneering evaluation of the natural history of PEI bridging to OLT as compared to TACE. METHODS: All consecutive cirrhotic patients with HCC enlisted for OLT (2011-2020) at a single center were analyzed. Patients were divided into three LRT modality groups: PEI, TACE, and PEI+TACE. The primary study outcome was waitlist dropout due to tumor progression beyond Milan criteria. A comparison of post-transplant outcomes of patients as stratified by LRT modality also was performed. RESULTS: One hundred twenty-nine patients were included (PEI=56, TACE=43, PEI+TACE=30). The dropout rate due to tumor progression was not different among the three groups: PEI=8.9%, TACE=14%, PEI+TACE=16.7% (p=0.54). Thirteen (76.4%) patients underwent OLT after successful downstaging (3 [75%] in the PEI group, 5 [83.3%] in the TACE group, and 5 [71.4%] in the PEI+TACE group). For the 96 patients undergoing OLT, 5-year post-transplant recurrence-free survival was PEI=55.6% vs. TACE=55.1% vs. PEI+TACE=71.4% (p=0.42). Complete/near-complete pathological response rate was similar among groups (p=0.82). CONCLUSION: Dropout rates and post-transplant recurrence-free survivals related to PEI were comparable to those of TACE. This study supports the use of PEI alone or in combination with TACE for HCC patients awaiting OLT whenever RFA is not an option.


Assuntos
Carcinoma Hepatocelular , Ablação por Cateter , Quimioembolização Terapêutica , Neoplasias Hepáticas , Transplante de Fígado , Humanos , Carcinoma Hepatocelular/cirurgia , Neoplasias Hepáticas/cirurgia , Quimioembolização Terapêutica/efeitos adversos , Etanol , Resultado do Tratamento , Estudos Retrospectivos
12.
Langenbecks Arch Surg ; 408(1): 231, 2023 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-37306803

RESUMO

PURPOSE: Although liver transplantation (LT) outcomes have improved significantly over the last decades, early vascular complications are still associated with elevated risks of graft failure. Doppler ultrasound (DUS) enables detection of vascular complications, provides hepatic artery Resistive Index (RI). The aim of our study was to evaluate the association of the RI parameters of DUS performed in the first post-transplant week with post-transplant outcomes. METHODS: All consecutive patients undergoing a first LT between 2001 and 2019 at a single center were included. Patients were divided into two groups: RI < 0.55 and RI ≥ 0.55. Patients were also divided according to the presence or absence of hepatic artery thrombosis (HAT). Graft survival was compared between groups. RESULTS: Overall, 338 patients were included. HAT occurred in 23 patients (6.8%), of which 7 were partial and 16, complete. Biliary complications were more common in patients with HAT (10 [43.5%]) vs. 38 [12.1%] [p < 0.001]). Graft survival was lower for patients with HAT (p = 0.047). Also, RI < 0.55 was associated with increased incidence of HAT (p < 0.001). Additionally, patients with RI < 0.55 on post-operative day 1 had decreased graft survival as compared to patients with RI > 0.55 (p = 0.041). RI on post-operative day 3 and 5 was not predictive of inferior graft outcomes. CONCLUSIONS: Intensive use of DUS in the early post-LT period offers the possibility of early diagnosis of vascular complications, guiding medical and surgical management of HAT. Additionally, according to our data, low RI (< 0.55) on the first postoperative day also is a predictor of HAT and decreased graft-survival.


Assuntos
Transplante de Fígado , Trombose , Humanos , Artéria Hepática , Sobrevivência de Enxerto , Ultrassonografia Doppler
13.
Int J Mol Sci ; 24(13)2023 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-37445965

RESUMO

Breast cancer is responsible for 25% of all cancers that affect women. Due to its high heterogeneity pattern in clinical diagnosis and its molecular profile differences, researchers have been seeking new targets and therapies, with more specificity and fewer side effects. Thus, one compound that has garnered our attention is trans-chalcone, which is naturally occurring in various plants and possesses promising biological properties, including antitumor effects. MiRNA is an extensive class of non-coding small, endogenous, and single-stranded RNAs, and it is involved in post-translational gene regulation. Therefore, the objective of this study was to investigate the effects of TChal on miRNAs expression and its relationship with anticancer activity against MCF-7. Initially, the trans-chalcone IC50 value was established by MTT assay for MCF-7and HaCat (non-cancer cell), in which we found out that it was 53.73 and 44.18 µM, respectively. Subsequently, we treated MCF-7 cells with trans-chalcone at its IC50 concentration and performed Mi-seq analysis, which unveiled 23 differentially expressed miRNAs. From this set, we selected five miRNAs (miR-25-5p, miR-27a-3p, miR-891a, miR-449a, and miR-4485) for further validation using qRT-PCR, guided by in silico analysis and their known association with tumorigenesis. In conclusion, our research provides valuable insights into the potential use of TChal to reveal MicroRNAs molecular targets that can be applied in breast cancer therapy.


Assuntos
Neoplasias da Mama , Chalconas , MicroRNAs , Humanos , Feminino , MicroRNAs/genética , MicroRNAs/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Células MCF-7 , Chalconas/farmacologia , Chalconas/uso terapêutico , Regulação Neoplásica da Expressão Gênica
14.
J Sci Food Agric ; 103(1): 125-134, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35821573

RESUMO

BACKGROUND: Pretreatments of drying can represent an alternative to minimize the negative aspect process on the dry samples. Thus, the influence of ethanol (ET) and freezing (FG) as drying pretreatments was analyzed for slices of papaya. The slices (5 mm) were submitted for drying kinetics (60 °C and 1.5 m s-1 ). Drying kinetics experimental data were fitted using Page's model and a diffusive model with boundary condition of types I and III. Also the thermophysical properties (thermal conductivity and specific heat) were determined and finally, the kinetics of ultrasound-assisted (40 kHz and 132 W) extraction of total phenolic compounds (TPCs) were realized. RESULTS: The combined method (ET + FG) was more efficient in reducing the drying time of papaya slices (48%) and the model 2 simulating the boundary condition of the third type (type III) showed the best fit to the experimental data. Effective diffusivity and convective coefficient were higher for ET + FG, where the maximum reduction in water content was 91% compared to fresh slices. The pretreatments did not influence the thermal conductivity, however, they were significant in the specific heat and in the extraction of TPCs, being higher in the time of 180 min. CONCLUSION: It was confirmed in the results presented that the combined pretreatment ET + FG is the most viable for drying papaya slices. Furthermore, it was found to be the most efficient in minimizing the loss of TPCs. Therefore, this pretreatment has great potential for application in the development of high value-added foods. © 2022 Society of Chemical Industry.


Assuntos
Carica , Etanol , Congelamento , Dessecação/métodos , Fenóis/química , Verduras
15.
Chem Res Toxicol ; 35(3): 522-528, 2022 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-35258279

RESUMO

Ethyl ester flavor additives are used in e-liquids to produce a citrus flavor. Although these compounds are considered safe as flavor additives, this only applies to oral consumption and not vaping operations, where they can decompose into potentially harmful compounds including carboxylic acids. Further decomposition of these carboxylic acids is expected to produce ketene, which is a strong respiratory poison that can cause fatal lung damage at low concentrations. This study develops a kinetic model of the thermal decomposition of ethyl ester flavor additives and simulates the decomposition of these compounds under vaping conditions. These results show that under normal operating conditions, it is unlikely for any harmful compounds to be present in-lung. However, at higher operating temperatures, there is the potential for acetic and butanoic acid to be present in the lungs at concentrations that cause irritation, and where repeated exposure may lead to bronchitis. At more extreme operating conditions it is possible for harmful levels of ketene to be produced such that it could cause fatal or severely detrimental effects upon repeated exposure. These high temperatures can be reached under "dry" operating conditions that arise as a result of improper use, particularly in user-modified e-cigarettes.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Venenos , Vaping , Ésteres , Aromatizantes/análise , Vaping/efeitos adversos
16.
Faraday Discuss ; 238(0): 475-490, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-35822523

RESUMO

Gas phase ion-molecule reactions are central to chemical processes across many environments. A feature of many of these reactions is an inverse relationship between temperature and reaction rate arising from a submerged barrier (an early reaction barrier that is below the energy of the separated reactants), which often arises due to a stable pre-reactive complex. While the thermodynamics and kinetics of many ion-molecule reactions have been extensively modelled, the reaction kinetics of ion-molecule reactions involving radical ions are less explored. In this investigation, the target reactions involve distonic radical ions, where the charge and radical moieties are separated within the molecular structure. Experimental rate coefficients for the reaction of either C2H2 or C2H4 with a suite of eighteen distonic radical ions are reported. Rate coefficients are modelled using potential energy schemes combined with a statistical reaction-rate (RRKM-ME) model. Second-order rate coefficients are in good agreement with experimental values with an average RMS deviation of 37% across three orders of magnitude. These predictions are generally sensitive to the relative energetics of the pre-reactive complex forward transition state but are relatively insensitive to the overall exothermicity of the covalent-addition product.

17.
Phys Chem Chem Phys ; 24(11): 6515-6524, 2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35257130

RESUMO

The complexity of Cu13, Ag13, and Au13 coinage-metal clusters was investigated through their energy contributions via a density functional theory study, considering improvements in the PBE functional, such as van der Waals (vdW) corrections, spin-orbit coupling (SOC), Hubbard term (+U), and their combinations. Investigating two-dimensional (planar 2D) and three-dimensional (distorted 3D, CUB - cuboctahedral, and ICO - icosahedral) configurations, we found that vdW corrections are dominant in modulating the stability swapping between 2D and ICO (3D) for Ag13 (Au13), whereas for Cu13 its role is increasing the relative stability between 2D (least stable) and 3D (most stable), setting ICO as the reference. Among the energy portions that constitute the relative total energy, the dimensionality difference correlates with the magnitude of the relative dispersion energy (large for 2D/ICO and small for 3D/ICO) as the causal factor responsible for an eventual stability swapping. For instance, empirical vdW corrections may favor Ag13 as ICO, while semi empirical ones tend to swap the stability by favoring 2D. The same tendency is observed for Au13, except when SOC is included, which enlarges the stability of 3D over 2D. Energy decomposition analysis combined with the natural orbitals for the chemical valence approach confirmed the correlations between the dimensionality difference and the magnitude of the relative dispersion energies. Our structural analysis protocol was able to capture the local distortion effects (or even their absence) through the quantification of the Hausdorff chirality measure. Here, ICO, CUB, and 2D are achiral configurations for all coinage-metal clusters, whereas Cu13 as 3D presents a slight chirality when vdW correction based on many body dispersion is used, at the same time Ag13 as 3D turned out to be chiral for all calculation protocols as evidence of the role of the chemical composition.

18.
J Phys Chem A ; 126(1): 101-108, 2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-34936357

RESUMO

Polycyclic aromatic hydrocarbons (PAHs) are intermediates in the formation of soot particles and interstellar grains. However, their formation mechanisms in combustion and interstellar environments are not fully understood. The production of tricyclic PAHs and, in particular, the conversion of a PAH containing a five-membered ring to one with a six-membered ring are of interest to explain PAH abundances in combustion processes. In the present work, resonant ionization mass spectrometry in conjunction with isotopic labeling is used to investigate the formation of the phenalenyl radical from acenaphthylene and methane in an electrical discharge. We show that in this environment the CH cycloaddition mechanism converts a five-membered ring to a six-membered ring. This mechanism can occur in tandem with other PAH formation mechanisms such as hydrogen abstraction/acetylene addition (HACA) to produce larger PAHs in flames and the interstellar medium.

19.
Lasers Surg Med ; 54(6): 883-894, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35366381

RESUMO

INTRODUCTION: Ischemic heart disease is the leading cause of death worldwide, and interventions to reduce myocardial infarction (MI) complications are widely researched. Photobiomodulation therapy (PBMT) has altered multiple biological processes in tissues and organs, including the heart. OBJECTIVES: This study aimed to assess the temporal effects of PBMT on cardiac fibrosis activation after MI in rats. In this proof-of-concept study, we monitored the change in expression patterns over time of genes and microRNAs (miRNAs) involved in the formation of cardiac fibrosis post-MI submitted to PBMT. MATERIALS AND METHODS: Experimental MI was induced, and PBMT was applied shortly after coronary artery ligation (laser light of wavelength 660 nm, 15 mW of power, energy density 22.5 J/cm2 , 60 seconds of application, irradiated area 0.785 cm2 , fluence 1.1 J/cm2 ). Ventricular septal samples were collected at 30 minutes, 3, 6, 24 hours, and 3 days post-MI to determine temporal PBMT's effects on messenger RNA (mRNA) expression associated with cardiac fibrosis activation and miRNAs expression. RESULTS: PBMT, when applied after ischemia, reversed the changes in mRNA expression of myocardial extracellular matrix genes induced by MI. Surprisingly, PBMT modified cardiac miRNAs expression related to fibrosis replacement in the myocardium. Expression correlations between myocardial mRNAs were assessed. The correlation coefficient between miRNAs and target mRNAs was also determined. A positive correlation was detected among miR-21 and transforming growth factor beta-1 mRNA. The miR-29a expression negatively correlated to Col1a1, Col3a1, and MMP-2 mRNA expressions. In addition, we observed that miR-133 and Col1a1 mRNA were negatively correlated. CONCLUSION: The results suggest that PBMT, through the modulation of gene transcription and miRNA expressions, can interfere in cardiac fibrosis activation after MI, mainly reversing the signaling pathway of profibrotic genes.


Assuntos
Terapia com Luz de Baixa Intensidade , MicroRNAs , Infarto do Miocárdio , Animais , Fibrose , MicroRNAs/genética , MicroRNAs/metabolismo , Infarto do Miocárdio/genética , Infarto do Miocárdio/metabolismo , Infarto do Miocárdio/radioterapia , RNA Mensageiro/genética , Ratos
20.
J Stroke Cerebrovasc Dis ; 31(1): 106173, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34700235

RESUMO

OBJECTIVE: Stroke is a neurological deficit of cerebrovascular origin, considered a 21st-century epidemic that causes functional changes in the human body. This study aimed to evaluate the stomatognathic system of patients after hemorrhagic stroke through the bite force, thickness, and skin temperature in the region of the masseter and temporalis muscles. MATERIAL AND METHODS: Twenty-four subjects were divided into groups: post-hemorrhagic stroke; with right side of the affected body (n = 12) and without the neurological disorder (n = 12). Maximum molar bite force was verified using a digital dynamometer. Muscle thickness was measured using ultrasound images obtained at rest and during maximal voluntary contraction of the masseter and temporalis muscles. Thermographic camera was used to record the thermographic patterns of the masseter and temporalis muscles. Data were subjected to Student's t-test (P < .05). RESULTS: The maximum molar bite force showed significant differences in the right (P = .04) and left (P = .03) sides, with a reduction in force in the post-hemorrhagic stroke group on the affected and unaffected sides. There was a significant difference (P < .05) in the thickness of the left temporal muscle at mandibular rest (P = .01) between groups. The post-hemorrhagic stroke group clinically presented greater muscle thickness in almost 100% of the muscles evaluated in both clinical conditions. There were no significant differences in skin temperature in the masseter and temporal muscles between the groups. CONCLUSIONS: Our results suggest functional changes in the stomatognathic system of subjects after a hemorrhagic stroke, especially concerning molar bite force and masticatory muscle thickness in the temporal muscle (unaffected side).


Assuntos
Acidente Vascular Cerebral Hemorrágico , Músculos da Mastigação , Força de Mordida , Acidente Vascular Cerebral Hemorrágico/fisiopatologia , Humanos , Músculos da Mastigação/diagnóstico por imagem , Músculos da Mastigação/fisiopatologia , Temperatura Cutânea , Músculo Temporal/diagnóstico por imagem , Músculo Temporal/fisiopatologia , Ultrassonografia
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