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1.
Environ Res ; 203: 111772, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34324851

RESUMO

Neonicotinoids (NEOs) are extensively applied in global agricultural production for pest control but have adverse effects on human health. In this study, the concentrations of six NEOs and three characteristic metabolites were investigated by collecting 200 serum samples from an elderly population in China. Results showed that the NEOs and their metabolites were widely detected (89%-98 %) in the serum samples from the osteoporosis (OP) (n = 120) and non-OP (n = 80) population, and their median concentrations ranged from 0.04 ng/mL to 5.99 ng/mL and 0.01 ng/mL to 2.02 ng/mL, respectively. N-desmethyl-acetamiprid (ACE-dm) was the most abundant NEOs in the serum samples. Gender-related differences were found in concentrations of most NEOs and their metabolites in serum, with males having higher target analytes than females. Significantly (p < 0.05) positive correlations were observed among most NEO concentrations, suggesting that exposure source of these substances is common or related. However, associations between the concentrations of characteristic metabolites and their corresponding NEOs were insignificant, probably because the exogenous intake are the primary sources of metabolites of NEOs instead of the internal biotransformation. The associations between NEO concentrations (i.e., ACE-dm, dinotefuran, and olefin-imidacloprid) and OP (OR = 2.33-6.92, 95 % CI = 0.37-16.9, p-trend < 0.05) indicate that NEO exposure is correlated with increased odds of prevalent OP. This study is the first to document the profiles of NEOs and their metabolites in serum samples collected from an elderly population in South China and examine the relationships between NEO exposure and OP.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34841845

RESUMO

In the field of space mechanical lubrication, to improve the reliability and life of space lubrication, solid lubricating film-liquid lubricant composite lubrication has been used in recent years. This lubrication method can improve the durability of sliding friction mating surfaces, reduce equipment wear, and extend the service life of motion mechanisms. However, due to unstable factors such as volatilization and creeping of liquid lubricants in microgravity and ultra-high-vacuum environments, the solid lubricating film wears out after long-term use and produces wear debris and other unfavorable factors. To solve the above problems, this study proposes a novel composite lubrication system constituting a MoS2 film in combination with a supramolecular gel. The tribological performance of this lubrication system establishes an extended service life with a lower wear rate compared to the MoS2 film, regardless of functioning in vacuum or atmospheric conditions. More importantly, the results of the irradiation experiment demonstrate that MoS2-gel exhibits better anticreep performance as compared to MoS2-oil when exposed to atomic oxygen and ultraviolet light for 4 h. The analysis of this composite lubrication mechanism also reveals the formation of a continuous transfer film on the surface of the friction pairs by virtue of the outstanding synergistic effect between the MoS2 film and the gel. MoS2 debris is present in the gel as an additive, and the gel is capable of replenishing automatically once the MoS2 film is depleted. Moreover, the strong anticreep properties of the gel are attributable to the multialkylated cyclopentane oil being trapped by the intricate reassembling of the gelator network. It is firmly believed that this novel MoS2-gel composite lubrication system may have good prospective applications in space and special machinery domains.

3.
J Agric Food Chem ; 69(41): 12314-12322, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34612625

RESUMO

Phytoferritin has a natural cagelike architecture for carrying bioactive molecules, and it is uniquely suited to function as a carrier due to its multiple interfaces and channels. In this study, a novel approach was proposed to prepare ferritin-salvianolic acid B-epigallocatechin gallate (EGCG) three-layer nanoparticles (FSE) through the steric hindrance of ferritin channels. Urea (30 mM) could expand the ferritin channel size evidenced by the improved iron release rate vo and promote the EGCG penetration into the ferritin cavity without disassembly of the ferritin cage. The encapsulation ratio of EGCG was 16.0 ± 0.14% (w/w). Salvianolic acid B attached to the outer interface of ferritin through weak bonds with a binding constant of (2.91 ± 0.04) × 105 M-1. The FSE maintained a spherical structure with a diameter of 12 nm. Moreover, when subjected to heat (40-70 °C) there was a significant increase in the stability of EGCG in the FSE due to the binding of salvianolic acid B. Through this interesting approach, two molecules are simultaneously attached and encapsulated in ferritin in a multilayer form under moderate conditions, which is conducive to the protection of unstable molecules for potential encapsulation and delivery utilization.


Assuntos
Catequina , Nanopartículas , Benzofuranos , Catequina/análogos & derivados , Ferritinas
4.
Chemosphere ; : 132563, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34653480

RESUMO

Bisphenols (BPs), benzophenone-type UV filters (BP-type UV filters), triclosan (TCS), and triclocarban (TCC) are endocrine-disrupting chemicals (EDCs) and commonly used in consumer and personal care products. In the present study, seven BPs, eight BP-type UV filters, TCS, and TCC were quantified in 196 paired urine and blood samples collected from young adults in South China. Benzophenone-7 and benzophenone-9 were not detected in all samples, while other target compounds were widely detected in 39%-96% of the urine and 14%-96% of the blood samples, and the median concentrations ranged from <0.02 (specific gravity adjusted: < 0.02) to 2.33 (2.05) ng/mL and <0.01-2.66 ng/mL in the urine and blood samples, respectively. Females had higher levels of most target analytes, and gender-related differences (p < 0.05) were found in the blood levels of benzophenone-2 (females vs. males: 0.84 vs. <0.01 ng/mL), ΣBP (sum of BP-type UV filters; 1.61 vs. 0.98 ng/mL), TCS (3.89 vs. 1.69 ng/mL), and ΣTC (sum of TCS and TCC; 5.77 vs. 3.02 ng/mL). We calculated the portioning of the target compounds between blood and urine (B/U ratios). The B/U ratios of bisphenol F, benzophenone-2, benzophenone-6, 4-hydroxy benzophenone, TCS, and TCC were higher than 1, showing that these analytes have higher enrichment capacities in human blood. To the best of our knowledge, this is the first study to simultaneously analyze the concentrations of BPs, BP-type UV filters, TCS, and TCC in the paired urine and blood samples of young adults in South China.

5.
J Immunother Cancer ; 9(9)2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34489334

RESUMO

BACKGROUND: A better understanding of the molecular mechanisms that manifest in the immunosuppressive tumor microenvironment (TME) is crucial for developing more efficacious immunotherapies for hepatocellular carcinoma (HCC), which has a poor response to current immunotherapies. Regulatory T (Treg) cells are key mediators of HCC-associated immunosuppression. We investigated the selective mechanism exploited by HCC that lead to Treg cells expansion and to find more efficacious immunotherapies. METHODS: We used matched tumor tissues and blood samples from 150 patients with HCC to identify key factors of Treg cells expansion. We used mass cytometry (CyTOF) and orthotopic cancer mouse models to analyze overall immunological changes after growth differentiation factor 15 (GDF15) gene ablation in HCC. We used flow cytometry, coimmunoprecipitation, RNA sequencing, mass spectrum, chromatin immunoprecipitation and Gdf15 -/-, OT-I and GFP transgenic mice to demonstrate the effects of GDF15 on Treg cells and related molecular mechanism. We used hybridoma technology to generate monoclonal antibody to block GDF15 and evaluate its effects on HCC-associated immunosuppression. RESULTS: GDF15 is positively associated with the elevation of Treg cell frequencies in patients wih HCC. Gene ablation of GDF15 in HCC can convert an immunosuppressive TME to an inflammatory state. GDF15 promotes the generation of peripherally derived inducible Treg (iTreg) cells and enhances the suppressive function of natural Treg (nTreg) cells by interacting with a previously unrecognized receptor CD48 on T cells and thus downregulates STUB1, an E3 ligase that mediates forkhead box P3 (FOXP3) protein degradation. GDF15 neutralizing antibody effectively eradicates HCC and augments the antitumor immunity in mouse. CONCLUSIONS: Our results reveal the generation and function enhancement of Treg cells induced by GDF15 is a new mechanism for HCC-related immunosuppression. CD48 is the first discovered receptor of GDF15 in the immune system which provide the possibility to solve the molecular mechanism of the immunomodulatory function of GDF15. The therapeutic GDF15 blockade achieves HCC clearance without obvious adverse events.

6.
J Oncol ; 2021: 2265475, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34335751

RESUMO

Purpose: This study aims to explore the function of metformin in hypopharyngeal squamous cell carcinoma (HSCC) and the underlying mechanism. Methods: Cell viability, colony formation, cell apoptosis, and cell cycle were investigated using cell counting kit-8 assay, colony formation, and flow cytometry assay. Gene expression was detected by quantitative real-time polymerase chain reaction and western blot. The target relationship was validated by dual-luciferase reporter assay or RNA immunoprecipitation assay. An animal study was implemented to clarify the effect of metformin in vivo. Results: Metformin suppressed HSCC cell viability and colony formation ability and induced cell cycle arrest and apoptosis, and circ_0003214 overexpression weakened these effects. Circ_0003214 regulated A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) expression via targeting miR-489-3p. Besides, miR-489-3p restoration reversed the role of circ_0003214, and ADAM10 knockdown reversed miR-489-3p inhibition-mediated effect. Moreover, metformin blocked tumor growth via the circ_0003214-miR-489-3p-ADAM10 axis in vivo. Conclusion: Metformin inhibits HSCC progression through the circ_0003214/miR-489-3p/ADAM10 pathway.

7.
Sci Total Environ ; 798: 149275, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34333440

RESUMO

Parabens, benzophenone (BP)-type UV filters, triclosan (TCS), and triclocarban (TCC) are commonly used in personal care products. Human exposure to these compounds has received increasing concern because of their adverse health effects. However, the levels of these chemicals in paired urine and indoor samples have never been simultaneously measured. In this work, eight parabens, eight BP-type UV filters, TCS, and TCC were measured in paired urine and indoor dust samples collected from university students and their dormitories in South China. The target analytes were commonly measured in urine (71%-100%) and indoor dust (30%-98%), with median concentrations ranging from 0.16 ng/mL to 19.3 ng/mL in urine and from <0.01 ng/g to 3700 ng/g in indoor dust samples. Females had high levels of most of these target compounds, and gender-related differences were found in the levels of most target analytes. Positive correlations were found in the levels of methylparaben, ethyl paraben, benzophenone-3, and TCS between urine and indoor dust samples. This finding suggested that indoor dust is an important source for human exposure to these compounds. The estimated daily intake (EDI) of these analytes in paired samples was also evaluated. The median EDI-urine values of target analytes varied in the range of 4.02-59,280 ng/kg bw/day. Females had higher median EDI-urine values for most of target analytes than males. In addition, the median EDI-indoor dust values of most target analytes in dust from female dormitories were higher than those in dust from male dormitories. Indoor dust ingestion only had minor contribution (<0.5%) to the total exposure. To the best of the authors' knowledge, this study is the first to simultaneously analyze the concentrations of parabens, BP-type UV filters, TCS, and TCC in the paired urine and indoor samples from university students in South China.


Assuntos
Triclosan , Benzofenonas , Carbanilidas , China , Poeira/análise , Feminino , Humanos , Masculino , Parabenos/análise , Estudantes , Triclosan/análise , Universidades
8.
Theranostics ; 11(17): 8185-8196, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34373736

RESUMO

Background: Efficient and specific induction of cell death in liver cancer is urgently needed. In this study, we aimed to design an exosome-based platform to deliver ferroptosis inducer (Erastin, Er) and photosensitizer (Rose Bengal, RB) into tumor tissues with high specificity. Methods: Exosome donor cells (HEK293T) were transfected with control or CD47-overexpressing plasmid. Exosomes were isolated and loaded with Er and RB via sonication method. Hepa1-6 cell xenograft C57BL/6 model was injected with control and engineered exosomes via tail vein. In vivo distribution of the injected exosomes was analyzed via tracking the fluorescence labeled exosomes. Photodynamic therapy was conducted by 532 nm laser irradiation. The therapeutic effects on hepatocellular carcinoma and toxic side-effects were systemically analyzed. Results: CD47 was efficiently loaded on the exosomes from the donor cells when CD47 was forced expressed by transfection. CD47 surface functionalization (ExosCD47) made the exosomes effectively escape the phagocytosis of mononuclear phagocyte system (MPS), and thus increased the distribution in tumor tissues. Erastin and RB could be effectively encapsulated into exosomes after sonication, and the drug-loaded exosomes (Er/RB@ExosCD47) strongly induced ferroptosis both in vitro and in vivo in tumor cells after irradiation of 532 nm laser. Moreover, compared with the control exosomes (Er/RB@ExosCtrl), Er/RB@ExosCD47 displayed much lower toxicity in liver. Conclusion: The engineered exosomes composed of CD47, Erastin, and Rose Bengal, induce obvious ferroptosis in hepatocellular carcinoma (HCC) with minimized toxicity in liver and kidney. The proposed exosomes would provide a promising strategy to treat types of malignant tumors.

9.
Appl Opt ; 60(16): 4654-4661, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34143022

RESUMO

Defects have significant influence on the impact fracture behavior of structures. In this paper, the real-virtual caustics method is used to study the impact fracture behavior of structures with elliptical arc defects under impact loading of the drop hammer, and the impact loading process is simultaneously analyzed. The research results show that impact loading of the drop hammer in this experiment is a multi-period dynamic loading process, and the fracture of specimens under impact loading of the drop hammer is an energy-controlled process. The running crack initiates under impact loading and propagates toward the elliptical arc defect. After reaching the end of the elliptical arc defect, the running crack arrests and accumulates energy, and then it initiates again and propagates toward the loading position. The greater the end curvature of the elliptical arc defect, the shorter the time for the running crack to stagnate and accumulate energy at the defect end, and the earlier the time for the running crack to initiate again at the defect end, the smaller the impact loading stress of the drop hammer and the dynamic stress intensity factor of running crack tip when the running crack initiates again at the defect end.

10.
Environ Res ; 199: 111175, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33964309

RESUMO

Neonicotinoid insecticides (NEOs) are widely used for pest control worldwide. The profile of NEOs in paired urine and indoor dust has not yet been reported in China. In this study, 40 paired samples (i.e., 160 urine and 40 indoor dust) were collected from university students and dormitories from Guangzhou City of China to measure the concentrations of six NEOs and their three metabolites. Target analytes were frequently detected in paired urine (81%-98%) and indoor dust (75%-95%) samples, with median concentrations ranging from 0.02 [specific gravity (SG) adjusted: 0.02] to 2.08 (SG-adjusted: 2.38) ng/mL in urine and from 0.05 to 2.74 ng/g in indoor dust. 5-Hydroxy-imidacloprid was predominant in urine, while N-desmethyl acetamiprid was predominant in indoor dust samples, accounting for 56% and 37%, respectively. 1-Methyl-3-(tetrahydro-3-furylmethyl) urea, a dinotefuran degradate, was measured for the first time in indoor dust, with the median level of 1.02 ng/g. Significant gender-related differences (p < 0.05) in the urinary concentrations of most NEOs were found. We calculated the estimated daily intake (EDI) of target compounds from urine and indoor measurements. The EDIs of target analytes varied among all urine and indoor dust samples, with median values ranging from 0.51 (SG-adjusted: 0.56) to 51.6 (SG-adjusted: 52.8) ng/kg bw/day and from 0.04 to 2.10 pg/kg bw/day, respectively. Moreover, the median EDIsurine of most target analytes in females were significantly higher than (p < 0.05) those in males. The median EDIsdust of target compounds in dust from female dormitories were slightly higher than that in dust from male dormitories. These findings indicated that females were more exposed to NEO than males. Thus, the potential health risks of exposure to NEOs and their metabolites in female adults should be addressed in future studies. To our knowledge, this study is the first to report the profiles of NEOs and their metabolites in paired urine and indoor dust samples from young adults in China.


Assuntos
Poluição do Ar em Ambientes Fechados , Inseticidas , China , Poeira/análise , Feminino , Habitação , Humanos , Inseticidas/análise , Masculino , Neonicotinoides/análise , Adulto Jovem
11.
Sensors (Basel) ; 21(9)2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33923320

RESUMO

Image denoising is a challenging task that is essential in numerous computer vision and image processing problems. This study proposes and applies a generative adversarial network-based image denoising training architecture to multiple-level Gaussian image denoising tasks. Convolutional neural network-based denoising approaches come across a blurriness issue that produces denoised images blurry on texture details. To resolve the blurriness issue, we first performed a theoretical study of the cause of the problem. Subsequently, we proposed an adversarial Gaussian denoiser network, which uses the generative adversarial network-based adversarial learning process for image denoising tasks. This framework resolves the blurriness problem by encouraging the denoiser network to find the distribution of sharp noise-free images instead of blurry images. Experimental results demonstrate that the proposed framework can effectively resolve the blurriness problem and achieve significant denoising efficiency than the state-of-the-art denoising methods.

12.
Acupunct Med ; 39(6): 656-662, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33715459

RESUMO

BACKGROUND: Bone loss induced by microgravity is a serious problem in space flight. However, the effects of acupuncture stimulation on osteoporosis induced by microgravity have not been studied. With the goal of developing an effective countermeasure, our aim was to evaluate the effects of electroacupuncture (EA) stimulation at BL20, BL23, and SP6 on osteoporosis induced by simulated microgravity in rats. METHODS: Thirty male Wistar rats (aged 10 weeks) were randomly divided into three groups: healthy control group (CON, n = 10), hind limb unloading by tail-suspension group (T-S, n = 10), and EA treatment group (TRE, n = 10). Rats in the T-S and TRE groups were subjected to tail-suspension at -30° for 30 days, while the CON group experienced freedom of activity. In this period, the TRE group received EA treatment at BL20, BL23, and SP6 for 30 min every other day, which continued for 30 days. The microarchitecture of the proximal tibia and the biomechanical features of the femur in the rats were analyzed. In addition, the levels of serum biomarkers bone alkaline phosphatase (BALP) and osteocalcin (BGP) were measured. RESULTS: Compared with the CON group, the value of bone volume/total volume (BV/TV) and trabecular number (Tb.N) of the tibias in the TRE group remarkably decreased (p < 0.01). However, these changes were markedly less than those of the T-S group after 4 weeks of EA treatment (p < 0.05). Moreover, the serum concentration of BGP in the TRE group was also significantly higher than that of the T-S group (p < 0.05). CONCLUSIONS: These findings indicate that EA stimulation at BL20, BL23, and SP6 retards osteoporosis induced by hind limb unloading in rats.

13.
Alzheimers Dement (N Y) ; 7(1): e12122, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33614893

RESUMO

Introduction: Hearing aid usage has been linked to improvements in cognition, communication, and socialization, but the extent to which it can affect the incidence and progression of dementia is unknown. Such research is vital given the high prevalence of dementia and hearing impairment in older adults, and the fact that both conditions often coexist. In this study, we examined for the first time the effect of the use of hearing aids on the conversion from mild cognitive impairment (MCI) to dementia and progression of dementia. Methods: We used a large referral-based cohort of 2114 hearing-impaired patients obtained from the National Alzheimer's Coordinating Center. Survival analyses using multivariable Cox proportional hazards regression model and weighted Cox regression model with censored data were performed to assess the effect of hearing aid use on the risk of conversion from MCI to dementia and risk of death in hearing-impaired participants. Disease progression was assessed with Clinical Dementia Rating Sum of Boxes (CDR-SB) scores. Three types of sensitivity analyses were performed to validate the robustness of the results. Results: MCI participants that used hearing aids were at significantly lower risk of developing all-cause dementia compared to those not using hearing aids (hazard ratio [HR] 0.73, 95% confidence interval [CI], 0.61 to 0.89; false discovery rate [FDR] P = 0.004). The mean annual rate of change (standard deviation) in CDR-SB scores for hearing aid users with MCI was 1.3 (1.45) points and significantly lower than for individuals not wearing hearing aids with a 1.7 (1.95) point increase in CDR-SB per year (P = 0.02). No association between hearing aid use and risk of death was observed. Our findings were robust subject to sensitivity analyses. Discussion: Among hearing-impaired adults, hearing aid use was independently associated with reduced dementia risk. The causality between hearing aid use and incident dementia should be further tested.

14.
Sci Total Environ ; 773: 145582, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33582343

RESUMO

Neonicotinoid insecticides (NEOs) are widely used for pest control worldwide. However, only a few studies have analyzed NEOs and their metabolites in blood samples, and no study has measured the concentrations of NEOs and their metabolites in paired urine and blood samples. In this study, six NEOs and three characteristic metabolites were detected in 196 paired urine and blood samples collected from young adults from China. The NEOs and their metabolites were widely detected in paired urine (67%-91%) and blood (64%-97%) samples, and the median levels ranged within 0.01-1.15 ng/mL in urine and 0.08-0.80 ng/mL in blood. Olefin-imidacloprid (Of-IMI) and 1-methyl-3-(tetrahydro-3-furylmethyl) urea (UF) were the most abundant target compounds in the urine (32.4%) and blood (26.4%) samples, respectively. Gender-related differences were observed in the concentrations of most NEOs and their metabolites in the urine and blood samples. The partitioning of target analytes between blood and urine (NEOs-B/NEOs-U ratios) was also calculated in this study. The B/U ratios of most NEOs and their metabolites were below 1, and positive correlations were observed between urine and blood in most levels of NEOs and their metabolites. This finding indicates that urinary levels are good predictors of human exposure to NEOs and their metabolites. The estimated daily intake (EDI) and the imidacloprid-equivalent (IMIeq) levels of NEOs and their metabolites in 196 young adults were also determined. The median EDI values (ng/kg bw/day) of ΣNEOs (sum of NEOs and their metabolites) and IMIeq in females (194.9 and 458.2) were slightly higher than (p > 0.05) those in males (157.1 and 439.7). This finding shows young adults are extensively exposed to NEOs and their metabolites. To our knowledge, this study is the first to report about NEOs and their metabolites in paired samples of urine and blood in China.


Assuntos
Inseticidas , Alcenos , China , Feminino , Humanos , Inseticidas/análise , Masculino , Neonicotinoides , Adulto Jovem
15.
Eur Arch Otorhinolaryngol ; 278(1): 141-148, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32638085

RESUMO

PURPOSE: Immune scores have been used as a prognostic factor for various types of cancer. However, the association between immune scores and the prognosis of laryngeal squamous cell cancer (LSCC) has not yet been investigated. This study aimed to explore the prognostic significance of immune scores and construct a clinical nomogram to predict the survival of patients with LSCC. METHODS: The clinicopathological characteristics and immune scores of 102 patients with LSCC were obtained from TCGA database and a nomogram was developed. C-index and calibration curves were applied to assess the performance of the model. RESULTS: Patients with higher immune scores had significantly better overall survival (OS). The prognostic nomogram presented a good performance in survival prediction. CONCLUSIONS: High immune scores are correlated with improved OS in patients with LSCC. In addition, the nomogram developed for this study may assist clinicians in the prognostic evaluation of patients with LSCC.


Assuntos
Suscetibilidade a Doenças/imunologia , Neoplasias de Cabeça e Pescoço/patologia , Neoplasias Laríngeas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Causalidade , China/epidemiologia , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Humanos , Neoplasias Laríngeas/diagnóstico , Neoplasias Laríngeas/mortalidade , Masculino , Pessoa de Meia-Idade , Nomogramas , Prognóstico , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Taxa de Sobrevida , Microambiente Tumoral/imunologia
16.
Neurobiol Learn Mem ; 177: 107358, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33285318

RESUMO

The perineuronal net (PNN) is a specialized type of extracellular matrix found in the central nervous system. The PNN forms on fast spiking neurons during postnatal development but the ontogeny of PNN development has yet to be elucidated. By studying the development and prevalence of the PNN in the juvenile and adult rat brain, we may be able to understand the PNN's role in development and learning and memory. We show that the PNN is fully developed in the deep cerebellar nuclei (DCN) of rats by P18. By using enzymatic digestion of the PNN with chondroitinase ABC (ChABC), we are able to study how digestion of the PNN affects cerebellar-dependent eyeblink conditioning in vivo and perform electrophysiological recordings from DCN neurons in vitro. In vivo degradation of the PNN resulted in significant differences in eyeblink conditioning amplitude and area. Female animals in the vehicle group demonstrated higher levels of conditioning as well as significantly higher post-probe conditioned responses compared to males in that group, differences not present in the ChABC group. In vitro, we found that DCN neurons with a disrupted PNN following exposure to ChABC had altered membrane properties, fewer rebound spikes, and decreased intrinsic excitability. Together, this study further elucidates the role of the PNN in cerebellar learning in the DCN and is the first to demonstrate PNN degradation may erase sex differences in delay conditioning.

17.
Head Neck ; 43(3): 928-941, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33247530

RESUMO

BACKGROUND: Circular RNAs (circRNAs) play critical roles in various types of cancer and chemosensitivity. METHODS: The expression levels of circ_0004507 and microRNA-873 (miR-873) were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The interaction between circ_0004507 and miR-873 was predicted by circinteractome and verified by dual-luciferase reporter assay and RNA pull-down assay. Xenograft tumor model was established to confirm the biological role of circ_0004507 in vivo. RESULTS: circ_0004507 was highly expressed and miR-873 was lowly expressed in laryngeal cancer tissues. circ_0004507 knockdown or miR-873 overexpression inhibited cell proliferation, migration and invasion, and increased apoptosis and cisplatin sensitivity in laryngeal cancer cells. miR-873 was identified as a direct target of circ_0004507. circ_0004507 interference inhibited tumor growth and promoted cisplatin sensitivity by upregulating miR-873 in vivo. CONCLUSION: Knockdown of circ_0004507 inhibited laryngeal cancer progression and cisplatin resistance by sponging miR-873, providing a potential target for laryngeal cancer therapy.


Assuntos
Neoplasias Laríngeas , MicroRNAs , RNA Circular , Membro 1 da Subfamília B de Cassetes de Ligação de ATP , Animais , Cisplatino/farmacologia , Progressão da Doença , Resistência a Múltiplos Medicamentos , Resistencia a Medicamentos Antineoplásicos , Humanos , Neoplasias Laríngeas/tratamento farmacológico , Neoplasias Laríngeas/genética , MicroRNAs/genética , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Ear Nose Throat J ; : 145561320969251, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33147061

RESUMO

AIM: Some obstructive sleep apnea (OSA) patients may have mandibular retrognathia (ANB > 4.7° and SNB < 76.2°). Currently, there are no studies that have compared the effectiveness of continuous positive airway pressure (CPAP) versus mandibular advancement device (MAD) in severe OSA patients with mandibular retrognathia. We explored the efficacy of CPAP versus MAD for the treatment of severe OSA patients with mandibular retrognathia. METHODS: A total of 105 patients were enrolled. Outcomes were assessed by using polysomnography, Epworth Sleepiness Scale (ESS), Snore Scale (SS), Self-rating Anxiety Scale (SAS), and compliance, before treatment and after 6 and 12 months of treatment. RESULTS: Continuous positive airway pressure was superior to MAD in improving polysomnographic outcomes and SS score, but reported compliance was higher on MAD. There is no significant difference between the 2 treatments in terms of ESS score and SAS score. Obstructive sleep apnea patients with mandibular retrognathia showed greater improvement than those without mandibular retrognathia in terms of apnea-hypopnea index and oxygen desaturation index after MAD. CONCLUSION: Continuous positive airway pressure and MAD are both effective in treating severe OSA patients with mandibular retrognathia. Mandibular advancement device is a good alternative to CPAP in severe OSA patients with mandibular retrognathia. Mandibular advancement device is more effective in treating OSA patients with mandibular retrognathia than those without. Trial registration: ChiCTR2000032541.

19.
Front Oncol ; 10: 537763, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33251130

RESUMO

Meningioma (MEN) is a common central nervous system disease. Accumulating evidence indicated that long non-coding RNA maternally expressed gene 3 (MEG3) participated in the progression of MEN. However, the potential mechanisms of MEG3 in altering the aggressive phenotypes of MEN need further exploration. Levels of MEG3, microRNA (miR)-29c, and A-kinase anchor protein 12 (AKAP12) were determined using quantitative real-time Polymerase Chain Reaction (qRT-PCR) assay. Dual-luciferase reporter and RNA immunoprecipitation (RIP) assays were performed to verify the relationship between miR-29c and MEG3 or AKAP12. The protein level of AKAP12 was detected by western blot. Moreover, cell-cycle arrest, migration, invasion, and proliferation were assessed by flow cytometry, wound healing, transwell assays, and CCK-8 assay, respectively. Levels of MEG3 and AKAP12 were downregulated, while miR-29c was effectively increased in MEN tissues and cell line. Mechanically, MEG3 was a sponge of miR-29c to regulate the expression of AKAP12. Functionally, increase of MEG3 diminished cell-cycle, migration, invasion, and proliferation in MEN cells, and reintroduction of miR-29c could eliminate these effects. In addition, AKAP12 depletion overturned the inhibitory effects of miR-29c absence on cell-cycle, migration, invasion, and proliferation in vitro. Also, AKAP12 was co-regulated by MEG3/miR-29c axis. MEG3 mediated the aggressive behaviors of MEN cells via miR-29c/AKAP12 axis, supporting that MEG3 served as a promising biomarker for the diagnosis and treatment of human MEN.

20.
Medicine (Baltimore) ; 99(40): e22596, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019479

RESUMO

BACKGROUND: The pathophysiologic of vascular malformations is still unclear, and the treatment of vascular malformations is a challenge. With improvement in the understanding of pathogenesis of vascular malformations, sirolimus has been a promising and effective treatment. As so far, there is absent convincing evidence to confirm the efficacy of sirolimus for vascular malformations. The purpose of this study was to evaluate the effectiveness and safety of sirolimus in the treatment of vascular malformations. METHODS: The literatures about the management of vascular malformations with sirolimus would be searched from databases of MEDLINE, EMBASE, PubMed, Web of Science, Clinicaltrials.org., Cochrane Library, China Biology Medicine Database (CBM), Wan Fang Database, China National Knowledge Infrastructure Database (CNKI), and VIP Science Technology Periodical Database. We will search each database from inception or 1995 to August 20, 2020. Two researchers worked independently on literature selection, data extraction and quality assessment. The efficacy and safety of sirolimus in the treatment of vascular malformations were the main outcomes. Adverse events after sirolimus were evaluated as the secondary outcomes. The included studies will be analyzed by Review Manager 5.3. If the results are applicable, meta-analysis would also be performed. RESULTS: The study will evaluate the efficacy and safety of sirolimus in the treatment of vascular malformations based on current evidence. CONCLUSION: The conclusion of this study will provide more reliable, evidence-based data for the use of sirolimus in the treatment of vascular malformations. PROSPERO REGISTRATION NUMBER: CRD42020167881.


Assuntos
Imunossupressores/uso terapêutico , Sirolimo/uso terapêutico , Malformações Vasculares/tratamento farmacológico , Gerenciamento de Dados , Feminino , Humanos , Imunossupressores/efeitos adversos , Masculino , Projetos de Pesquisa , Segurança , Sirolimo/efeitos adversos , Serina-Treonina Quinases TOR/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Resultado do Tratamento , Malformações Vasculares/fisiopatologia
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