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INTRODUCTION: Polynucleotides (PN) are becoming more prominent in aesthetic medicine. However, the structural characteristics of PN have not been published and PN from different companies may have different structural characteristics. This study aimed to elucidate the structural attributes of DOT™ PN and distinguish differences with polydeoxyribonucleotides (PDRN) using high-resolution scanning electron microscopy (SEM) imaging. MATERIALS AND METHODS: DOT™ PN was examined using a Quanta 3-D field emission gun (FEG) Scanning Electron Microscope (SEM). Sample preparation involved cryogenic cooling, cleavage, etching, and metal coating to facilitate high-resolution imaging. Cryo-FIB/SEM techniques were employed for in-depth structural analysis. RESULTS: PDRN exhibited an amorphous structure without distinct features. In contrast, DOT™ PN displayed well-defined polyhedral shapes with smooth, uniformly thick walls. These cells were empty, with diameters ranging from 3 to 8 micrometers, forming a seamless tessellation pattern. DISCUSSION: DOT™ PN's distinct geometric tessellation design conforms to the principles of biotensegrity, providing both structural reinforcement and integrity. The presence of delicate partitions and vacant compartments hints at possible uses in the field of pharmaceutical delivery systems. Within the realms of beauty enhancement and regenerative medicine, DOT™ PN's capacity to bolster cell growth and tissue mending could potentially transform approaches to rejuvenation treatments. Its adaptability becomes apparent when considering its contributions to drug administration and surgical procedures. CONCLUSION: This study unveils the intricate structural scaffold features of DOT™ PN for the first time, setting it apart from PDRN and inspiring innovation in biomedicine and materials science. DOT™ PN's unique attributes open doors to potential applications across healthcare and beyond.
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Polinucleotídeos , Humanos , Microscopia Eletrônica de VarreduraRESUMO
Decreased medial cheek fat volume during aging leads to loss of a youthful facial shape. Increasing facial volume by methods such as adipose-derived stem cell (ASC) injection can produce facial rejuvenation. High-intensity focused ultrasound (HIFU) can increase adipogenesis in subcutaneous fat by modulating cilia on ASCs, which is accompanied by increased HSP70 and decreased NF-κB expression. Thus, we evaluated the effect of HIFU on increasing facial adipogenesis in swine (n = 2) via modulation of ASC cilia. Expression of CD166, an ASC marker, differed by subcutaneous adipose tissue location. CD166 expression in the zygomatic arch (ZA) was significantly higher than that in the subcutaneous adipose tissue in the mandible or lateral temporal areas. HIFU was applied only on the right side of the face, which was compared with the left side, where HIFU was not applied, as a control. HIFU produced a significant increase in HSP70 expression, decreased expression of NF-κB and a cilia disassembly factor (AURKA), and increased expression of a cilia increasing factor (ARL13B) and PPARG and CEBPA, which are the main regulators of adipogenesis. All of these changes were most prominent at the ZA. Facial adipose tissue thickness was also increased by HIFU. Adipose tissue volume, evaluated by magnetic resonance imaging, was increased by HIFU, most prominently in the ZA. In conclusion, HIFU increased ASC marker expression, accompanied by increased HSP70 and decreased NF-κB expression. Additionally, changes in cilia disassembly and length and expression of adipogenesis were observed. These results suggest that HIFU could be used to increase facial volume by modulating adipogenesis.
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Adipogenia , Animais , Suínos , Cílios/metabolismo , Tecido Adiposo/citologia , Tecido Adiposo/metabolismo , Células-Tronco/metabolismo , Células-Tronco/citologia , Face , Gordura Subcutânea/citologia , Gordura Subcutânea/metabolismo , Adipócitos/metabolismo , Adipócitos/citologia , NF-kappa B/metabolismoRESUMO
Within circulating fluidized bed (CFB) processes, gas and solid behaviors are mutually affected by operating conditions. Therefore, understanding the behaviors of gas and solid materials inside CFB processes is required for designing and operating those processes. In addition, in order to minimize the environmental impact, modeling to reduce pollutants such as SOx emitted from those processes is essential, and simulation reproduction is necessary for optimization, but little is known. In this study, the gas and solid behaviors in a pilot-scale circulating fluidized bed combustor were investigated by using computational particle fluid dynamics (CPFD) numerical simulation based on the multiphase particle-in-cell (MP-PIC) method under oxy-fuel combustion conditions. In particular, the combustion and in-situ desulfurization reactions simultaneously were considered in this CPFD model. Effect of fluidization number (ULS/Umf) was investigated through the comparison of particle circulation rates with regards to the loop seal flux plane and bed height in the standpipe. In addition, the effects of parameters (temperature, Ca/S molar ratio, and particle size distribution), sensitive indicators for the desulfurization efficiency of limestone, were confirmed. Based on the cycle of the thermodynamic equilibrium curve of limestone, it is suggested that direct and indirect desulfurization occur simultaneously under different operating conditions in CFB, creating an environment in which various reactions other than desulfurization can occur. Addition of the reaction equations (i.e., porosity, diffusion) to the established simple model minimizes uncertainty in the results. Furthermore, the model can be utilized to optimize in-situ desulfurization under oxy-CFB operating conditions.
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Poluentes Atmosféricos , Poluentes Ambientais , Porosidade , Poluentes Atmosféricos/análise , Carbonato de Cálcio , TemperaturaRESUMO
Increased serum C-reactive protein (CRP) levels at the time of diagnosis predicted worse prognosis in patients with non-tuberculous mycobacterial pulmonary disease (NTM-PD). Approximately one-quarter of the patients with NTM-PD had higher than normal CRP levels, and this elevation led to a higher risk of death.
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Pneumopatias , Infecções por Mycobacterium não Tuberculosas , Humanos , Micobactérias não Tuberculosas , Prognóstico , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Infecções por Mycobacterium não Tuberculosas/microbiologia , Estudos Retrospectivos , Pneumopatias/microbiologia , BiomarcadoresRESUMO
BACKGROUND: Polynucleotides (PN) are increasingly used for the treatment of facial erythema in the Republic of Korea. However, there are limited pre-clinical and clinical data on the efficacy of polynucleotides for facial erythema. In this study, we investigated the current practice and perceived effectiveness of polynucleotide treatment for facial erythema among cosmetic physicians. METHODS: By conducting a survey among clinicians who use PN in clinical practice, we explored the current practices and assessed the perceived effectiveness of polynucleotides in treating facial erythema. RESULTS: A total of 557 physicians who used polynucleotides for facial erythema participated in the survey. Polynucleotides were used by 84.4%, 66.4%, and 47.4% of physicians for facial erythema caused by inflammatory facial dermatosis, repeated laser/microneedle radiofrequency, and steroid overuse, respectively. Among those users, 88.1%, 90%, and 83.7% respectively in those same categories answered that polynucleotides were "highly effective" or "effective." Furthermore, they agreed that polynucleotides have the following properties: wound healing/regeneration (95.8%), protection of skin barrier (92.2%), hydration (90.5%), vascular stabilization (81.0%), and anti-inflammation (79.5%). CONCLUSION: Our findings showed that cosmetic physicians in the Republic of Korea have used PN as a part of combination treatment for facial erythema resulting from inflammatory facial dermatosis and repeated laser/ microneedle radiofrequency, rather than from steroid overuse. Also, most clinicians agreed that PN was effective for treatment of facial erythema. Given the lack of pre-clinical and clinical trial evidence, the empirical responses of practicing physicians provide useful information to guide clinical practice and further research.
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Cosméticos , Dermatoses Faciais , Humanos , Resultado do Tratamento , Eritema/tratamento farmacológico , Eritema/etiologia , Cicatrização , EsteroidesRESUMO
Multi-step traffic forecasting has always been extremely challenging due to constantly changing traffic conditions. Advanced Graph Convolutional Networks (GCNs) are widely used to extract spatial information from traffic networks. Existing GCNs for traffic forecasting are usually shallow networks that only aggregate two- or three-order node neighbor information. Because of aggregating deeper neighborhood information, an over-smoothing phenomenon occurs, thus leading to the degradation of model forecast performance. In addition, most existing traffic forecasting graph networks are based on fixed nodes and therefore need more flexibility. Based on the current problem, we propose Dynamic Adaptive Deeper Spatio-Temporal Graph Convolutional Networks (ADSTGCN), a new traffic forecasting model. The model addresses over-smoothing due to network deepening by using dynamic hidden layer connections and adaptively adjusting the hidden layer weights to reduce model degradation. Furthermore, the model can adaptively learn the spatial dependencies in the traffic graph by building the parameter-sharing adaptive matrix, and it can also adaptively adjust the network structure to discover the unknown dynamic changes in the traffic network. We evaluated ADSTGCN using real-world traffic data from the highway and urban road networks, and it shows good performance.
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INTRODUCTION: Hyperhidrosis, causing excessive sweat, can be treated with Botulinum neurotoxin injection. Botulinum toxin, an effective and safe treatment for hyperhidrosis, unfortunately involves significant pain due to multiple injections. This study aims to propose a more efficient and less painful approach to nerve blocks for relief, by identifying optimal injection points to block the median nerve, thereby enhancing palmar hyperhidrosis treatment. METHODS: This study, involving 52 Korean cadaver arms (mean age 73.5 years), measured the location of the median nerve relative to the transverse line at the pisiform level to establish better nerve block injection sites. RESULTS: In between the extensor carpi radialis and palmaris longus, the median nerve was located at an average distance of 47.39 ± 6.43 mm and 29.39 ± 6.43 mm from the transverse line at the pisiform level. DISCUSSION: To minimize discomfort preceding the botulinum neurotoxin injection, we recommend the optimal injection site for local anesthesia to be located 4 cm distal to the transverse line of the pisiform, within the tendons of the palmaris longus and flexor carpi radialis muscles.
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Toxinas Botulínicas Tipo A , Hiperidrose , Humanos , Idoso , Anestesia Local/efeitos adversos , Nervo Mediano , Mãos , Hiperidrose/tratamento farmacológico , Hiperidrose/complicações , Dor/etiologiaRESUMO
BACKGROUND AND OBJECTIVES: This study describes the intramuscular nerve branching of the deltoid muscle in relation to shoulder surface anatomy, with the aim of providing essential information regarding the most appropriate sites for botulinum neurotoxin injection during shoulder line contouring. METHODS: The modified Sihler's method was used to stain the deltoid muscles (16 specimens). The intramuscular arborization areas of the specimens were demarcated using the marginal line of the muscle origin and the line connecting the anterior and posterior upper edges of the axillary region. RESULTS: The intramuscular neural distribution of the deltoid muscle had the greatest arborization patterns in the area between the horizontal 1/3 and 2/3 lines of the anterior and posterior deltoid bellies, and 2/3 to axillary line in middle deltoid bellies. The greatest part of the posterior circumflex artery and axillary nerve ran below the areas with the highest aborizations. CONCLUSION: We propose that botulinum neurotoxin injections should be administered in the area between the 1/3 and 2/3 lines of the anterior and posterior deltoid bellies, and 2/3 to axillary line on middle deltoid bellies. Accordingly, clinicians will ensure minimal dose injections and fewer adverse effects of the botulinum neurotoxin injection. Deltoid intramuscular injections, such as vaccines and trigger point injections, should ideally be adapted according to our results.
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Toxinas Botulínicas , Ombro , Humanos , Músculo Deltoide , Axila , Injeções Intramusculares/efeitos adversosRESUMO
BACKGROUND: The antitumor effects of natural killer cells, helper T cells, and cytotoxic T cells after cancer surgery were reported previously. This study hypothesized that propofol-based anesthesia would have fewer harmful effects on immune cells than volatile anesthetics-based anesthesia during colorectal cancer surgery. METHODS: In total, 153 patients undergoing colorectal cancer surgery were randomized and included in the analysis. The primary outcome was the fraction of circulating natural killer cells over time in the propofol and sevoflurane groups. The fractions of circulating natural killer, type 1, type 17 helper T cells, and cytotoxic T cells were investigated. The fractions of CD39 and CD73 expressions on circulating regulatory T cells were investigated, along with the proportions of circulating neutrophils, lymphocytes, and monocytes. RESULTS: The fraction of circulating natural killer cells was not significantly different between the propofol and sevoflurane groups until 24 h postoperatively (20.4 ± 13.4% vs. 20.8 ± 11.3%, 17.9 ± 12.7% vs. 20.7 ± 11.9%, and 18.6 ± 11.6% vs. 21.3 ± 10.8% before anesthesia and after 1 and 24 h after anesthesia, respectively; difference [95% CI], -0.3 [-4.3 to 3.6], -2.8 [-6.8 to 1.1], and -2.6 [-6.2 to 1.0]; P = 0.863, P = 0.136, and P = 0.151 before anesthesia and after 1 and 24 h, respectively). The fractions of circulating type 1 and type 17 helper T cells, cytotoxic T cells, and CD39+ and CD73+ circulating regulatory T cells were not significantly different between the two groups. The neutrophil to lymphocyte ratio in both groups remained within the normal range and was not different between the groups. CONCLUSIONS: Propofol-based anesthesia was not superior to sevoflurane-based anesthesia in terms of alleviating suppression of immune cells including natural killer cells and T lymphocytes during colorectal cancer surgery.
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Anestésicos Inalatórios/farmacologia , Anestésicos Intravenosos/farmacologia , Neoplasias Colorretais/cirurgia , Propofol/farmacologia , Sevoflurano/farmacologia , Linfócitos T Reguladores/imunologia , Adulto , Anestésicos Inalatórios/imunologia , Anestésicos Intravenosos/imunologia , Neoplasias Colorretais/imunologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Propofol/imunologia , Estudos Prospectivos , Sevoflurano/imunologia , Linfócitos T Reguladores/efeitos dos fármacosRESUMO
Nicotinamide nucleotide transhydrogenase (NNT) is involved in decreasing melanogenesis through tyrosinase degradation induced by cellular redox changes. Nicotinamide is a component of coenzymes, such as NAD+, NADH, NADP+, and NADPH, and its levels are modulated by NNT. Vitamin C and polydeoxyribonucleotide (PDRN) are also known to decrease skin pigmentation. We evaluated whether a mixture of nicotinamide, vitamin C, and PDRN (NVP-mix) decreased melanogenesis by modulating mitochondrial oxidative stress and NNT expression in UV-B-irradiated animals and in an in vitro model of melanocytes treated with conditioned media (CM) from UV-B-irradiated keratinocytes. The expression of NNT, GSH/GSSG, and NADPH/NADP+ in UV-B-irradiated animal skin was significantly decreased by UV-B radiation but increased by NVP-mix treatment. The expression of NNT, GSH/GSSG, and NADPH/NADP+ ratios decreased in melanocytes after CM treatment, although they increased after NVP-mix administration. In NNT-silenced melanocytes, the GSH/GSSG and NADPH/NADP+ ratios were further decreased by CM compared with normal melanocytes. NVP-mix decreased melanogenesis signals, such as MC1R, MITF, TYRP1, and TYRP2, and decreased melanosome transfer-related signals, such as RAB32 and RAB27A, in UV-B-irradiated animal skin. NVP-mix also decreased MC1R, MITF, TYRP1, TYRP2, RAB32, and RAB27A in melanocytes treated with CM from UV-irradiated keratinocytes. The expression of MC1R and MITF in melanocytes after CM treatment was unchanged by NNT silencing. However, the expression of TYRP1, TYRP2, RAB32, and RAB27A increased in NNT-silenced melanocytes after CM treatment. NVP-mix also decreased tyrosinase activity and melanin content in UV-B-irradiated animal skin and CM-treated melanocytes. In conclusion, NVP-mix decreased mitochondrial oxidative stress by increasing NNT expression and decreased melanogenesis by decreasing MC1R/MITF, tyrosinase, TYRP1, and TYRP2.
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NADP Trans-Hidrogenases , Animais , Ácido Ascórbico/metabolismo , Ácido Ascórbico/farmacologia , Dissulfeto de Glutationa/metabolismo , Melaninas , Melanócitos/metabolismo , Monofenol Mono-Oxigenase/metabolismo , NADP/metabolismo , NADP Trans-Hidrogenases/metabolismo , Niacinamida/metabolismo , Niacinamida/farmacologia , Polidesoxirribonucleotídeos/metabolismo , Vitaminas/metabolismoRESUMO
It is well-known that increased oxidative stress caused by ultraviolet B (UV-B) radiation induces melanogenesis and activates metalloproteinases (MMPs), which degrade collagen and elastin fibers, leading to decreased skin elasticity. Various antioxidant agents, such as vitamin C and niacinamide, have been evaluated for use as treatments for photoaging or skin pigmentation. In this study, we evaluated the ability of a topical liquid formula of polydeoxyribonucleotide (PDRN), vitamin C, and niacinamide (PVN) delivered via a microneedling therapy system (MTS) to attenuate photoaging and pigmentation by increasing nuclear factor erythroid 2-like 2 (NRF2)/heme oxygenase-1 (HO-1) and decreasing MMP expression in a UV-B-radiated animal model. The effects of the PVN were compared with those of individual PDRN and hydroquinone (HQ) compounds. The expression of NRF2/HO-1 significantly increased in response to HQ, PDRN, and PVN in UV-B-radiated animal skin. The activity of nicotinamide adenine dinucleotide phosphate hydrogen oxidase decreased in response to HQ, PDRN, and PVN, and the superoxide dismutase activity increased. The expression of tumor protein p53 and microphthalmia-associated transcription factor and tyrosinase activity decreased in response to HQ, PDRN, and PVN, and this decrease was accompanied by decreased melanin content in the skin. The expression of nuclear factor kappa-light-chain enhancer of activated B cells and MMP2/3/9 decreased in response to HQ, PDRN, and PVN in UV-B-radiated skin. However, the expression of collagen type I α1 chain and the amount of collagen fibers that were evaluated by Masson's trichrome staining increased in response to HQ, PDRN, and PVN. The contents of elastin fibers, fibrillin 1/2 and fibulin 5 increased in response to HQ, PDRN, and PVN. In conclusion, PVN delivered via MTS led to decreased melanogenesis and destruction of collagen and elastin fibers by MMPs, and, thus, PVN decreased skin pigmentation and increased skin elasticity.
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Ácido Ascórbico/química , Fator 2 Relacionado a NF-E2/metabolismo , Niacinamida/administração & dosagem , Polidesoxirribonucleotídeos/administração & dosagem , Fenômenos Fisiológicos da Pele/efeitos dos fármacos , Pigmentação da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Pele/metabolismo , Biomarcadores , Elasticidade , Expressão Gênica , Imuno-Histoquímica , Metaloproteinases da Matriz/genética , Metaloproteinases da Matriz/metabolismo , Melaninas/biossíntese , Fator 2 Relacionado a NF-E2/genética , Raios UltravioletaRESUMO
Recently, with the rise of deep learning, text classification techniques have developed rapidly. However, the existing work usually takes the entire text as the modeling object and pays less attention to the hierarchical structure within the text, ignoring the internal connection between the upper and lower sentences. To address these issues, this paper proposes a Bert-based hierarchical graph attention network model (BHGAttN) based on a large-scale pretrained model and graph attention network to model the hierarchical relationship of texts. During modeling, the semantic features are enhanced by the output of the intermediate layer of BERT, and the multilevel hierarchical graph network corresponding to each layer of BERT is constructed by using the dependencies between the whole sentence and the subsentence. This model pays attention to the layer-by-layer semantic information and the hierarchical relationship within the text. The experimental results show that the BHGAttN model exhibits significant competitive advantages compared with the current state-of-the-art baseline models.
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Peroxisomes play an essential role in cellular homeostasis by regulating lipid metabolism and the conversion of reactive oxygen species (ROS). Several peroxisomal proteins, known as peroxins (PEXs), control peroxisome biogenesis and degradation. Various mutations in the PEX genes are genetic causes for the development of inheritable peroxisomal-biogenesis disorders, such as Zellweger syndrome. Among the peroxins, PEX1 defects are the most common mutations in Zellweger syndrome. PEX1 is an AAA-ATPase that regulates the recycling of PEX5, which is essential for importing peroxisome matrix proteins. However, the post-transcriptional regulation of PEX1 is largely unknown. Here, we showed that heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1) controls PEX1 expression. In addition, we found that depletion of HNRNPA1 induces autophagic degradation of peroxisome, which is blocked in ATG5-knockout cells. In addition, depletion of HNRNPA1 increased peroxisomal ROS levels. Inhibition of the generation of peroxisomal ROS by treatment with NAC significantly suppressed pexophagy in HNRNPA1-deficient cells. Taken together, our results suggest that depletion of HNRNPA1 increases peroxisomal ROS and pexophagy by downregulating PEX1 expression.
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ATPases Associadas a Diversas Atividades Celulares/metabolismo , Ribonucleoproteína Nuclear Heterogênea A1/metabolismo , Macroautofagia/fisiologia , Proteínas de Membrana/metabolismo , Peroxissomos/metabolismo , ATPases Associadas a Diversas Atividades Celulares/genética , Proteína 5 Relacionada à Autofagia/antagonistas & inibidores , Proteína 5 Relacionada à Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Células Cultivadas , Regulação para Baixo , Técnicas de Inativação de Genes , Células HCT116 , Células HeLa , Ribonucleoproteína Nuclear Heterogênea A1/deficiência , Ribonucleoproteína Nuclear Heterogênea A1/genética , Humanos , Macroautofagia/genética , Proteínas de Membrana/genética , Processamento Pós-Transcricional do RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Síndrome de Zellweger/genética , Síndrome de Zellweger/metabolismoRESUMO
BACKGROUND: Deep neuromuscular blockade (NMB) may reduce muscle injury and related inflammation. The inflammation is one of the pathophysiological processes of peri-operative complications. OBJECTIVE: To compare the degree of inflammation and related postoperative complications including postoperative delirium (POD) and peri-operative bleeding according to the degree of NMB during general anaesthesia for total hip replacement. DESIGN: A prospective, single-blind, randomised controlled trial. SETTING: Tertiary, university hospital, single centre. PATIENTS: Eighty-two patients undergoing total hip replacement surgery were included in the final analysis. INTERVENTIONS: Moderate (Mod) and deep (Deep) NMB groups. MAIN OUTCOME MEASURES: The changes in inflammatory cytokines were measured. The incidence of POD was evaluated by using confusion assessment method (CAM). The differences of postoperative bleeding and peri-operative oxygenation in both groups were also measured. RESULTS: The NMB reversal duration was significantly longer in the Mod NMB group than in the Deep NMB group. Changes in interleukin-6 were significantly smaller in the Deep NMB group than in the Mod NMB group (Pâ<â0.001). The incidence of POD was not significantly different between groups (34 versus 17% in Mod and Deep NMB groups, respectively; Pâ=â0.129). The amount of postoperative bleeding until postoperative day 2 was significantly greater in the Mod NMB group than in the Deep NMB group (Pâ=â0.027). CONCLUSION: Our findings suggest that inflammation related to peri-operative complications could be associated with the depth of NMB during total hip replacement. However, the incidence of POD might not be associated to the depth of NMB. TRIAL REGISTRATION: National Library of Medicine (NLM) at the National Institutes of Health (NIH) of United States. (Identifier: NCT02507609). Online address: http://clinicaltrials.gov.
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Artroplastia de Quadril , Delírio , Bloqueio Neuromuscular , Idoso , Artroplastia de Quadril/efeitos adversos , Citocinas , Delírio/diagnóstico , Delírio/epidemiologia , Delírio/etiologia , Método Duplo-Cego , Humanos , Estudos Prospectivos , Método Simples-CegoRESUMO
BACKGROUND: This study was designed to investigate the effect of cluster differentiation (CD)39 and CD73 inhibitors on the expresion of tumour-associated macrophages (TAMs), M1- versus M2-tumour phenotypes in mice with colon cancer. METHODS: An in vivo study of co-culture with colon cancer cells and immune cells from the bone marrow (BM) of mice was performed. After the confirmation of the effect of polyoxotungstate (POM-1) as an inhibitor of CD39 on TAMs, the mice were randomly divided into a control group without POM-1 and a study group with POM-1, respectively, after subcutaneous injection of CT26 cells. On day 14 after the injection, the mice were sacrificed, and TAMs were evaluated using fluorescence-activated cell sorting. RESULTS: In the in vivo study, the co-culture with POM-1 significantly increased the apoptosis of CT26 cells. The cell population from the co-culture with POM-1 showed significant increases in the expression of CD11b+ for myeloid cells, lymphocyte antigen 6 complex, locus C (Ly6C+) for monocytes, M1-tumour phenotypes from TAMs, and F4/80+ for macrophages. In the in vivo study, tumour growth in the study group with POM-1 was significantly limited, compared with the control group without POM-1. The expressions of Ly6C+ and major histocompatibility complex class II+ for M1-tumour phenotypes from TAMs on F4/80+ from the tumour tissue in the study group had significantly higher values compared with the control group. CONCLUSION: The inhibition of CD39 with POM-1 prevented the growth of colon cancer in mice, and it was associated with the increased expression of M1-tumour phenotypes from TAMs in the cancer tissue.
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Apirase/antagonistas & inibidores , Neoplasias do Colo/prevenção & controle , Polímeros/farmacologia , Macrófagos Associados a Tumor/efeitos dos fármacos , Compostos de Tungstênio/farmacologia , Animais , Antígenos CD , Apoptose , Proliferação de Células , Neoplasias do Colo/metabolismo , Neoplasias do Colo/patologia , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Prognóstico , Células Tumorais Cultivadas , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/patologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Melanosomes are specialized membrane-bound organelles that are involved in melanin synthesis. Unlike melanosome biogenesis, the melanosome degradation pathway is poorly understood. Among the cellular processes, autophagy controls degradation of intracellular components by cooperating with lysosomes. In this study, we showed that ursolic acid inhibits skin pigmentation by promoting melanosomal autophagy, or melanophagy, in melanocytes. We found that B16F1 cells treated with ursolic acid suppressed alpha-melanocyte stimulating hormone (α-MSH) stimulated increase in melanin content and activated autophagy. In addition, we found that treatment with ursolic acid promotes melanosomal degradation, and bafilomycin A1 inhibition of autophagosome-lysosome fusion blocked the removal of melanosomes in α-MSH-stimulated B16F1 cells. Furthermore, depletion of the autophagy-related gene 5 (ATG5) resulted in significant suppression of ursolic acid-mediated anti-pigmentation activity and autophagy in α-MSH-treated B16F1 cells. Taken together, our results suggest that ursolic acid inhibits skin pigmentation by increasing melanosomal degradation in melanocytes.
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Autofagia/efeitos dos fármacos , Melanoma Experimental/patologia , Melanossomas/patologia , Pigmentação da Pele/efeitos dos fármacos , Triterpenos/farmacologia , Animais , Linhagem Celular Tumoral , Melaninas/biossíntese , Melanossomas/efeitos dos fármacos , Camundongos , Triterpenos/química , alfa-MSH/farmacologia , Ácido UrsólicoRESUMO
Introduction: This study was designed to assess the effect of repetitive exposure to intravenous anesthetic agents on the immunity in mice. Materials and Methods: The mice were divided into six groups: three intravenous anesthetic agents groups (dexmedetomidine, midazolam and propofol groups), and three corresponding control groups (CD, CM, and CP groups). The intravenous injections were administered once per day for 5 days. The immunity of mice was checked after the last intravenous injection. Histopathology and immunochemistry of liver and kidneys were evaluated. Cytokine levels in the blood was also checked. vs. evaluated with cytokine levels in the blood. Results: Cluster of differentiation (CD)4+ T cells were significantly less expressed in dexmedetomidine and propofol groups, compared with the corresponding control groups [34.08 ± 5.63% in the dexmedetomidine group vs. 59.74 ± 8.64% in the CD group, p < 0.05; 25.28 ± 7.28% in the propofol group vs. 61.12 ± 2.70% in the Cp group, p < 0.05]. Apoptosis of CD4+ T cells was increased significantly in dexmedetomidine and propofol groups, compared with the corresponding control groups. Histopathological findings of liver and kidneys did not show any specific differences of any of three intravenous anesthetic agents groups with their corresponding control groups, although immunohistochemical examination indicated significantly lower expression of Toll-like receptor-4 from liver and kidneys in dexmedetomidine and propofol groups. The cytokine levels were not different between the groups. Conclusion: Repetitive exposure to dexmedetomidine and propofol reduced the expression of CD4+ T cells but did not induce any significant liver or kidney injuries.
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Anestésicos Intravenosos/farmacologia , Imunidade Adaptativa/efeitos dos fármacos , Animais , Linfócitos T CD4-Positivos/efeitos dos fármacos , Linfócitos T CD4-Positivos/metabolismo , Dexmedetomidina/administração & dosagem , Dexmedetomidina/farmacologia , Ensaio de Imunoadsorção Enzimática , Imuno-Histoquímica , Rim/efeitos dos fármacos , Rim/imunologia , Fígado/efeitos dos fármacos , Fígado/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Midazolam/farmacologia , Propofol/administração & dosagem , Propofol/farmacologiaRESUMO
An understanding of the location and depth of the facial artery (FA) is essential in aesthetic surgery and various cosmetic procedures. The purpose of this study was to clarify the three-dimensional (3D) topography of the exposed segment (ES) of the FA and to provide information to help minimize complications during clinical procedures. From 50 embalmed adult cadavers, the undissected and dissected hemifaces were scanned and reconstructed using the 3D scanner. Then the topographic location of the ES was identified and measured from the superimposed the 3D images. The ES was observed in 82% of the whole specimens. The exposure patterns of the ES were examined, and classified into three types: Type I, one site exposed pattern (74%); Type II, two sites exposed pattern (8%); and Type III, nonexposed pattern (18%). The extent of the ES was located at 2.2 mm above and 4.2 mm below the cheilion (Ch)-otobasion inferius line, and 20.0 to 25.2 mm from the Ch on the lateral aspect. In the frontal view, the average distance from the mid-pupillary line to the ES was 7.1 mm, and from the lateral canthal line to the ES was 6.1 mm. The ES was 7.6 mm below the skin surface. The results of this study will help to provide safe guidelines for filler injections as well as selecting the safe regions in various clinical procedures. Clin. Anat. 33:257-264, 2020. © 2019 Wiley Periodicals, Inc.
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Artérias/anatomia & histologia , Artérias/diagnóstico por imagem , Face/irrigação sanguínea , Face/diagnóstico por imagem , Idoso , Variação Anatômica , Cadáver , Feminino , Humanos , Imageamento Tridimensional , Masculino , Cirurgia PlásticaRESUMO
Mitochondria are essential for providing the energy necessary for neuronal function. Dysregulation of mitochondrial dynamics has been linked with the pathogenesis of many neurodegenerative diseases. Dynamin related protein 1 (Drp1) participates in fission activity in the mitochondria, and post-translational modifications to Drp1 modulate complex mitochondrial dynamics. However, the regulation of Drp1 at the post-transcriptional level remains poorly understood. In this study, we found that the RNA-binding protein Hu antigen R (HuR) post-transcriptionally regulates Drp1 expression. HuR interacts with Drp1 mRNA at its 3' untranslated region. Depletion of HuR reduces Drp1 expression, which leads to mitochondrial elongation in SH-SY5Y neuroblastoma cells. In contrast, ectopic expression of HuR enhances Drp1 expression, which promotes mitochondrial fragmentation in response to treatment with the mitochondrial complex 1 inhibitor MPP+. In addition, depletion of HuR suppressed the generation of mitochondrial ROS and cytotoxicity in MPP+ treated cells. Taken together, these findings suggest that HuR controls mitochondrial morphology via regulation of Drp1.
Assuntos
Dinaminas/genética , Proteína Semelhante a ELAV 1/genética , Regulação Neoplásica da Expressão Gênica , Mitocôndrias/genética , Dinâmica Mitocondrial/genética , Proteínas de Ligação a RNA/genética , 1-Metil-4-fenilpiridínio/farmacologia , Regiões 3' não Traduzidas/genética , Linhagem Celular Tumoral , Dinaminas/metabolismo , Proteína Semelhante a ELAV 1/metabolismo , Herbicidas/farmacologia , Humanos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , Ligação Proteica , Interferência de RNA , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismoRESUMO
Background: This study investigated the effects of propofol and isoflurane on endoplasmic reticulum (ER) stress in an animal model under general anaesthesia. Methods: Rats were randomly divided into Propofol and Isoflurane groups. Anaesthesia was maintained with propofol for Propofol group or isoflurane for Isoflurane group during 3 h. ER stress from lymphocytes in blood and tissues was evaluated between two groups after euthanasia. Reactive oxygen species (ROS) from lymphocytes in blood and tissues, and cytokines in blood were also checked. An immunohistochemical assay for ER stress marker from tissues was performed. Results: After anaesthesia, the levels of CCAAT-enhancer-binding protein homologous proteins (CHOP) in blood and liver were significantly higher in Isoflurane group, compared to Propofol group [blood, 31,499 ± 4,934 (30,733, 26,441-38,807) mean fluorescence intensity (MFI) in Isoflurane group vs. 20,595 ± 1,838 (20,780, 18,866-22,232) MFI in Propofol group, p = 0.002; liver, 28,342 ± 5,535 (29,421, 23,388-32,756) MFI in Isoflurane group vs. 20,004 ± 2,155 (19,244, 18,197-22,191) MFI in Propofol group, p = 0.020]. ROS in blood was significantly higher in Isoflurane group, compared to Propofol group. However, cytokines in blood and immunohistochemical assays in tissues were similar between groups. Conclusion: Significant higher of ER stress from blood and liver were observed in rats under anaesthesia with isoflurane, compared to those that received propofol. ROS from blood also showed significant higher under anaesthesia with isoflurane. However, these findings were not associated with any changes in cytokines in blood or immunohistochemical assay in tissues.