Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 54
Filtrar
1.
World J Clin Cases ; 12(10): 1793-1798, 2024 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-38660069

RESUMO

BACKGROUND: Whether hyperbaric oxygen therapy (HBOT) can cause paradoxical herniation is still unclear. CASE SUMMARY: A 65-year-old patient who was comatose due to brain trauma underwent decompressive craniotomy and gradually regained consciousness after surgery. HBOT was administered 22 d after surgery due to speech impairment. Paradoxical herniation appeared on the second day after treatment, and the patient's condition worsened after receiving mannitol treatment at the rehabilitation hospital. After timely skull repair, the paradoxical herniation was resolved, and the patient regained consciousness and had a good recovery as observed at the follow-up visit. CONCLUSION: Paradoxical herniation is rare and may be caused by HBOT. However, the underlying mechanism is unknown, and the understanding of this phenomenon is insufficient. The use of mannitol may worsen this condition. Timely skull repair can treat paradoxical herniation and prevent serious complications.

2.
Pharmaceuticals (Basel) ; 17(3)2024 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-38543077

RESUMO

BACKGROUND: Breast cancer is a commonly diagnosed cancer worldwide. Human MutT homolog 1 (MTH1) is found to be elevated in breast tumors and cancer cells need MTH1 for survival. Pharmacological inhibition of MTH1 may be potentially beneficial in the treatment of breast cancer. METHODS: MA-24 was screened by malachite green colorimetric assay for MTH1 inhibitors and the kinetic characteristics of MA-24 were assessed. The features of MA-24's binding with MTH1 were ascertained through molecular docking, and the cytotoxic activity of MA-24 was validated in vitro and in vivo. Target engagement assays, comet assay, and Western blot confirmed the intracellular target and mechanism of MA-24. RESULTS: MA-24 shows potent antitumor bioactivity both in vitro and in vivo. MA-24 competitively inhibited the MTH1 and further induced DNA strand breaks, leading to increased apoptosis of cancer cells depending on the upregulation of the cleaved-caspase 3-cleaved-PARP axis. In particular, MA-24 exhibited a powerful efficacy and safety in vivo (tumor growth inhibition rate: 61.8%). CONCLUSIONS: MA-24 possesses a broad spectrum of breast cancer cytotoxicity and offered valuable insights for overcoming the challenges of chemotherapy-related toxicity, which holds great potential for the further development MA-24 as an anti-cancer drug.

3.
Aesthetic Plast Surg ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532201

RESUMO

BACKGROUND: Autologous fat transplantation, widely used in cosmetic and reparative surgery for volumetric enhancements, faces challenges with its inconsistent long-term survival rates. The technique's efficacy, crucial for its development, is hindered by unpredictable outcomes. Enriching fat grafts with adipose-derived stem cells (ADSCs) shows promise in improving survival efficiency. OBJECTIVES: This study aimed to explore the potential of receptor-interacting protein kinase 3 (RIP3) kinase inhibitors as a pretreatment for ADSCs in enhancing autologous fat graft retention over a long term. METHODS: ADSCs were isolated, cultured under normal or oxygen-glucose deprivation conditions, and mixed with particulate fat grafts to form distinct experimental groups in female nude mice. Fat graft mass and volume, along with underlying mechanisms, were evaluated using quantitative reverse transcription polymerase chain reaction (RT-qPCR), immunohistochemistry, and Western blot analysis. RESULTS: The experimental group, pretreated with RIP3 kinase inhibitors, had higher graft mass and volume, greater adipocyte integrity, and increased peroxisome proliferator-activated receptor gamma (PPARγ) mRNA levels than control groups. Furthermore, the experimental group demonstrated lower expression of necroptosis pathway proteins in the short term and an ameliorated inflammatory response as indicated by interleukin-1 beta (IL-1ß), interleukin-10 (IL-10) mRNA levels, and histological analyses. Notably, enhanced neovascularization was evident in the experimental group. CONCLUSIONS: These findings suggest that RIP3 kinase inhibitor pretreatment of ADSCs can improve fat graft survival, promote adipocyte integrity, potentially decrease inflammation, and enhance neovascularization. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

4.
Int J Biol Sci ; 20(5): 1578-1601, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38481806

RESUMO

Background: The application of chimeric antigen receptor (CAR) NK cells in solid tumors is hindered by lack of tumor-specific targets and inefficient CAR-NK cell efficacy. Claudin-6 (CLDN6) has been reported to be overexpressed in ovarian cancer and may be an attractive target for CAR-NK cells immunotherapy. However, the feasibility of using anti-CLDN6 CAR-NK cells to treat ovarian cancer remains to be explored. Methods: CLDN6 expression in primary human ovarian cancer, normal tissues and cell lines were detected by immunohistochemistry and western blot. Two types of third-generation CAR NK-92MI cells targeting CLDN6, CLDN6-CAR1 NK-92MI cells with domains containing self-activated elements (NKG2D, 2B4) and CLDN6-CAR2 NK-92MI cells with classical domains (CD28, 4-1BB) were constructed by lentivirus transfection, sorted by flow cytometry and verified by western blot and qPCR. OVCAR-3, SK-OV-3, A2780, Hey and PC-3 cells expressing the GFP and luciferase genes were transduced. Subcutaneous and intraperitoneal tumor models were established via NSG mice. The ability of CLDN6-CAR NK cells to kill CLDN6-positive ovarian cancer cells were evaluated in vitro and in vivo by live cell imaging and bioluminescence imaging. Results: Both CLDN6-CAR1 and CLDN6-CAR2 NK-92MI cells could specifically killed CLDN6-positive ovarian cancer cells (OVCAR-3, SK-OV-3, A2780 and Hey), rather than CLDN6 negative cell (PC-3), in vitro. CLDN6-CAR1 NK-92MI cells with domains containing self-activated elements (NKG2D, 2B4) exhibited stronger cytotoxicity than CLDN6-CAR2 NK-92MI cells with classical domains (CD28, 4-1BB). Furthermore, CLDN6-CAR1 NK cells could effectively eliminate ovarian cancer cells in subcutaneous and intraperitoneal tumor models. More importantly, CAR-NK cells combined with immune checkpoint inhibitors, anti-PD-L1, could synergistically enhance the antitumor efficacy of CLDN6-targeted CAR-NK cells. Conclusions: These results indicate that CLDN6-CAR NK cells possess strong antitumor activity and represent a promising immunotherapeutic modality for ovarian cancer.


Assuntos
Claudinas , Neoplasias Ovarianas , Receptores de Antígenos Quiméricos , Humanos , Animais , Camundongos , Feminino , Receptores de Antígenos Quiméricos/genética , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/metabolismo , Linhagem Celular Tumoral , Apoptose , Subfamília K de Receptores Semelhantes a Lectina de Células NK/metabolismo , Antígenos CD28/metabolismo , Células Matadoras Naturais , Imunoterapia/métodos , Imunoterapia Adotiva/métodos
5.
Anal Chem ; 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38335969

RESUMO

The combined application of nanozymes and surface-enhanced Raman scattering (SERS) provides a promising approach to obtain label-free detection. However, developing nanomaterials with both highly efficient enzyme-like activity and excellent SERS sensitivity remains a huge challenge. Herein, we proposed one-step synthesis of Mo2N nanoparticles (NPs) as a "two-in-one" substrate, which exhibits both excellent peroxidase (POD)-like activity and high SERS activity. Its mimetic POD activity can catalyze the 3,3',5,5'-tetramethylbenzidine (TMB) molecule to SERS-active oxidized TMB (ox-TMB) with high efficiency. Furthermore, combining experimental profiling with theory, the mechanism of POD-like activity and SERS enhancement of Mo2N NPs was explored in depth. Benefiting from the outstanding properties of Mo2N NPs, a versatile platform for indirect SERS detection of biomarkers was developed based on the Mo2N NPs-catalyzed product ox-TMB, which acts as the SERS signal readout. The feasibility of this platform was validated using glutathione (GSH) and target antigens alpha-fetoprotein antigen (AFP) and carcinoembryonic antigen (CEA) as representatives of small molecules with a hydroxyl radical (·OH) scavenging effect and proteins with a low Raman scattering cross-section, respectively. The limits of detection of GSH, AFP, and CEA were as low as 0.1 µmol/L, 89.1, and 74.6 pg/mL, respectively. Significantly, it also showed application in human serum samples with recoveries ranging from 96.0 to 101%. The acquired values based on this platform were compared with the standard electrochemiluminescence method, and the relative error was less than ±7.3. This work not only provides a strategy for developing highly active bifunctional nanomaterials but also manifests their widespread application for multiple biomarkers analysis.

6.
Sci Total Environ ; 916: 170208, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38246372

RESUMO

The lockdowns implemented during the coronavirus disease 2019 (COVID-19) pandemic provide a unique opportunity to investigate the impact of emission sources and meteorological conditions on the trans-boundary transportation of black carbon (BC) aerosols to the Tibetan Plateau (TP). In this study, we conducted an integrative analysis, including in-situ observational data, reanalysis datasets, and numerical simulations, and found a significant reduction in the trans-boundary transport of BC to the TP during the 2020 pre-monsoon season as a result of the lockdowns and restrictive measures. Specifically, we observed a decrease of 0.0211 µgm-3 in surface BC concentration over the TP compared to the 2016 pre-monsoon period. Of this reduction, approximately 6.04 % can be attributed to the decrease in emissions during the COVID-19 pandemic, surpassing the 4.47 % decrease caused by changes in meteorological conditions. Additionally, the emission reductions have weakened the trans-boundary transport of South Asia BC to the TP by 0.0179 µgm-2s-1; indicating that the recurring spring atmospheric pollution from South Asia to the TP will be alleviated through the reduction of anthropogenic emissions. Moreover, it is important to note that BC deposition on glaciers contributes significantly to glacier melting due to its enrichment, posing a threat to the water sustainability of the TP. Therefore, urgent measures are needed to reduce emissions from adjacent regions to preserve the TP as the "Asian Water Tower."


Assuntos
Poluentes Atmosféricos , COVID-19 , Humanos , Tibet/epidemiologia , Pandemias , Poluentes Atmosféricos/análise , Monitoramento Ambiental , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Aerossóis e Gotículas Respiratórios , Fuligem/análise , Carbono/análise , Água/análise
7.
Arch Gynecol Obstet ; 309(2): 679-688, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38032411

RESUMO

PURPOSE: This study aimed to compare the effect of gonadotropin-releasing hormone agonist (GnRHa) trigger alone versus dual trigger comprising GnRHa and low-dose human chorionic gonadotropin (hCG) on reproductive outcomes in patients with polycystic ovary syndrome (PCOS) who received the freeze-all strategy. METHODS: A total of 615 cycles were included in this retrospective cohort study. Propensity score matching (PSM) was performed to control potential confounding factors between GnRHa-trigger group (0.2 mg GnRHa) and dual-trigger group (0.2 mg GnRHa plus 1000/2000 IU hCG) in a 1:1 ratio. Multivariate logistic regression was applied to estimate the association between trigger methods and reproductive outcomes. RESULTS: After PSM, patients with dual trigger (n = 176) had more oocytes retrieved, mature oocytes, and 2PN embryos compared to that with GnRHa trigger alone. However, the oocytes maturation rate, normal fertilization rate, and frozen embryos between the two groups were not statistically different. The incidence of ovarian hyperstimulation syndrome (OHSS) (14.8% vs. 2.8%, P < 0.001) and moderate/severe OHSS (11.4% vs. 1.7%, P < 0.001) were significantly higher in dual-trigger group than in GnRHa-alone group. Logistic regression analysis showed the adjusted odds ratio of dual trigger was 5.971 (95% confidence interval 2.201-16.198, P < 0.001) for OHSS. The pregnancy and single neonatal outcomes were comparable between the two groups (P > 0.05). CONCLUSION: For PCOS women with freeze-all strategy, GnRHa trigger alone decreased the risk of OHSS without damaging oocyte maturation and achieved satisfactory pregnancy outcomes.


Assuntos
Síndrome de Hiperestimulação Ovariana , Síndrome do Ovário Policístico , Gravidez , Recém-Nascido , Humanos , Feminino , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/tratamento farmacológico , Fertilização in vitro/métodos , Indução da Ovulação/métodos , Estudos Retrospectivos , Pontuação de Propensão , Hormônio Liberador de Gonadotropina/farmacologia , Gonadotropina Coriônica/farmacologia , Síndrome de Hiperestimulação Ovariana/epidemiologia , Síndrome de Hiperestimulação Ovariana/prevenção & controle , Oócitos , Taxa de Gravidez
8.
Int J Biol Macromol ; 247: 125573, 2023 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-37442502

RESUMO

The high viscosity of heavy oil made it difficult to exploit and transport heavy oil in pipeline. In this research, N-[(2-hydroxy-3-trimethylammonium) propyl] O-stearoyl chitosan tetraphenylboride (sc-CTS-st) was synthesized from chitosan, 2, 3-epoxy-propyl trimethyl ammonium chloride, sodium tetraphenylboron and stearyl chloride. sc-CTS-st contains long chain saturated aliphatic hydrocarbon, hydroxyl group and benzene ring, which could be dissolved in heavy oil fully and interacted with asphaltene. At 50 °C, the viscosity of heavy oil could be reduced to 13,800 mPa·s at most, with a viscosity reduction rate of 57.54 %. SEM and XRD showed that sc-CTS-st could affect the supramolecular accumulation structure of asphaltenes. Using FT-IR, sc-CTS-st could interact with asphaltene in the form of hydrogen bonds using the polar parts of the molecule, thereby weakening the self-association between asphaltene molecules. Molecular simulation was used to demonstrate the interaction mechanism between chitosan derivatives and asphaltenes. sc-CTS-st interacted with asphaltene through chemical bonding and influenced the self-association of asphaltene molecules. In addition, the non-polar portion of sc-CTS-st molecules could form a coating on the outside of the asphaltenes stacking structure, thus shielding or reducing the polarity of the stacking structure surface.


Assuntos
Quitosana , Hidrocarbonetos Policíclicos Aromáticos , Viscosidade , Espectroscopia de Infravermelho com Transformada de Fourier , Hidrocarbonetos Policíclicos Aromáticos/química
9.
J Craniofac Surg ; 34(7): 2217-2221, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37365693

RESUMO

Fat tissue has been widely used as a filler material during plastic surgery, but unpredictable fat retention remains a significant concern. Fat tissue is vulnerable to ischemia and hypoxia, but it always has waiting time before injection in the operation theater. Apart from transferring fat tissue as quickly as possible after harvesting, washing the aspirate with cool normal saline is often used. However, the mechanisms of cool temperature acting on adipose tissue have yet to be fully elucidated. Herein, this study aims to explore the effect of preservation at different temperatures on the inflammatory profile of adipose tissue. Inguinal adipose tissue of rats was collected and cultured in vitro under 4°C, 10°C, and room temperature for 2 hours. The proportion of damaged adipocytes and an array of cytokines were determined. We observed that the damage rate of the adipocyte membrane was slightly higher at room temperature, but there was no significant difference, while we noticed increased IL-6 and MCP-1 levels in adipose tissue at room temperature ( P <0.01). The 4°C and 10°C cool temperatures may offer protection against proinflammatory states during the adipose tissue preserved in vitro.


Assuntos
Adipócitos , Tecido Adiposo , Ratos , Animais , Temperatura , Temperatura Baixa , Citocinas
10.
Food Chem ; 399: 133918, 2023 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-35994858

RESUMO

A core-shell magnetic sulfonatocalix[6]arene covalently cross-linked polymer was proposed as a magnetic adsorbent, combined with ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) for the enrichment and determination of epoxy derivatives in canned foods. The adsorbent has high density of host-guest recognition functional groups, abundant binding sites and suitable cavity size, showing good extraction performance for epoxy derivatives. Quantum chemical simulation calculations provedmultiple interaction forces in the adsorption process. Theextractionparameterswere investigated. Under optimized experimental conditions, 13 kinds of target analytes showed low detection limits (0.0072-0.023 ng/g) and good precisions (RSDs of 0.8 %-9.4 %). This method has been successfully applied to the simultaneous determination of 13 kinds of epoxy derivatives in different food samples including canned beverage, fish, meat, and milk powder. Satisfactory recoveries (74.9 %-118 %) were obtained. The results showed the potential application prospects in the enrichment and detection of hazardous substances in food.


Assuntos
Éter , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão/métodos , Alimentos em Conserva/análise , Glicerol , Éteres de Glicerila , Indicadores e Reagentes , Fenômenos Magnéticos , Polímeros/análise , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos
11.
Anal Chem ; 94(34): 11889-11897, 2022 08 30.
Artigo em Inglês | MEDLINE | ID: mdl-35973129

RESUMO

The DNA origami-mediated self-assembly strategy has emerged as a powerful tool in surface-enhanced Raman spectroscopy (SERS). However, these self-assembly approaches typically do not possess high detection specificity. Herein, a novel strategy based on adenosine triphosphate (ATP)-responsive strand displacement (ARSD) coupling with DNA origami/AuNPs for SERS analysis of microcystin-LR (MC-LR) is presented. In the presence of MC-LR and ATP molecules, nucleic acid sensing structures fabricated with anti-MC-LR aptamer (T1) and ATP aptamer (T2) were triggered to release the remaining ATP. In addition, DNA origami-assisted assembly results in the formation of homogeneous plasmonic nanostructures for Raman enhancement via strong plasmonic coupling. After the binding in the gaps of functionalized DNA origami/AuNPs, the Raman shift of the ATP molecules becomes detectable, leading to increased SERS intensity in 734 cm-1. A linear response to MC-LR was obtained in the concentration range of 1.56-50 µg·L-1, and the limit of detection (LOD) was 0.29 µg·L-1. Combined with the solid-phase extraction sample pretreatment for extraction and 10-fold concentration, this proposed method was successfully used to detect MC-LR type in real lake-water samples with good recoveries of 98.4-116% and relative standard deviations of 1.9-6.7%. Furthermore, for the detection of MC-LR in contaminated lake-water samples, the results of the developed method and ultrahigh-performance liquid chromatography-tandem mass spectrometry were found to be in agreement with relative errors between -12 and 2.4%. The proposed strategy provides a sensitive recognition and signal amplification platform for trace MC-LR analysis as well as innovative nucleic acid sensing structures for toxin analysis more generally.


Assuntos
Técnicas Biossensoriais , Nanopartículas Metálicas , Trifosfato de Adenosina , Técnicas Biossensoriais/métodos , DNA , Ouro/química , Limite de Detecção , Toxinas Marinhas , Nanopartículas Metálicas/química , Microcistinas/análise , Análise Espectral Raman , Água/química
12.
Aesthetic Plast Surg ; 46(5): 2526-2538, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35552479

RESUMO

OBJECTIVE: In this study, we investigate the biological characteristics of ADSCs from the liposuction area in patients with hemifacial atrophy in vitro. METHODS: ADSCs were respectively extracted from the donor site of patients with hemifacial atrophy and healthy ones. ADSCs of two groups were respectively tested for proliferation ability, phenotype, multipotency, migration ability, self-repair ability, apoptosis, and autophagy. Exosomes extracted from the supernatant of two groups were detected by NTA particle size, electron microscopy (TEM), and WB for CD63 and TSG10, respectively. RESULTS: CCK-8 showed a statistically less increase in cell proliferation in PHA-ADSCs after the sixth day. ADSCs in both groups had typical phenotypes and multidirectional abilities. PHA-ADSCs exhibited weaker droplet formation. The cell migration ability in PHA-ADSCs was weaker tested by Transwell assay. The live/dead proportion calculated by ImageJ following calcein-AM/PI double staining revealed live cells in PHA-ADSCs was 46.11% compared with 54.21% in NORM-ADSCs after OGD treatment. A significant down-regulation of ATG7 and ATG12 and a higher percentage of apoptosis were found in PHA-ADSCs. A significant up-regulation of BAX occurred in PHA-ADSCs.ARPC5 expression in the PHA group was extremely distinct down-regulated.CDKN1A and CDKN2A expression in the PHA group was significantly up-regulated.WB analyses confirmed that both groups' ADSCs-Exosomes surface markers CD63 and TSG101 were positively expressed but varied significantly. CONCLUSIONS: PHA-ADSCs exhibited a poorer proliferation ability, higher apoptosis percentage, weaker lipid droplets formation, weaker cell migration, poorer intolerance to OGD, aging earlier, and weaker self-renewal and repairability.PHA-ADSCs-Exosomes showed low expressions of CD63 and TSG101.This study provides strong evidence that the addition of exosomes with specific cytokines can improve the fat survival rate after fat filling in patients with hemifacial atrophy. NO LEVEL ASSIGNED: This journal requires that authors 42 assign a level of evidence to each submission to which 43 Evidence-Based Medicine rankings are applicable. This 44 excludes Review Articles, Book Reviews, and manuscripts 45 that concern Basic Science, Animal Studies, Cadaver 46 Studies, and Experimental Studies. For a full description of 47 these Evidence-Based Medicine ratings, please refer to the 48 Table of Contents or the online Instructions to Authors 49 https://www.springer.com/00266 .


Assuntos
Hemiatrofia Facial , Lipectomia , Animais , Sincalida , Proteína X Associada a bcl-2 , Tecido Adiposo , Células-Tronco , Citocinas
13.
J Hazard Mater ; 432: 128742, 2022 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-35338931

RESUMO

Carcinogens in food samples show great potential threat to human health due to their wide distribution and high carcinogenicity. In this work, branched AuCu nanoalloy doped mesoporous graphitic carbon nitride hybrid membrane (mpg-C3N4/AuCu) was fabricated for SERS analysis of carcinogens including benzidine and zearalenone in food. The AuCu was in-situ grown on mpg-C3N4 to form mpg-C3N4/AuCu composites. The as-fabricated mpg-C3N4/AuCu membrane can effectively combined synergistic effect of localized surface plasmon resonance properties of branched AuCu nanoalloy and semiconductor characteristics of mpg-C3N4. The limit of detection for crystal violet is 1.0 ng/L with enhancement factor of 3.7 × 108. The mechanism of high SERS activity of mpg-C3N4/AuCu membrane was investigated by density functional theory simulations. The mpg-C3N4/AuCu membrane was used for direct determination of benzidine, and indirect determination of zearalenone with 3,3',5,5'-tetramethylbenzidine as markers in food. The limits of detection of SERS method were 0.14 and 0.03 µg/L for benzidine and zearalenone, respectively. It provides a new strategy for design and fabrication of high-quality SERS substrates for carcinogens analysis.


Assuntos
Ouro , Zearalenona , Carcinógenos , Cobre/química , Grafite , Humanos , Compostos de Nitrogênio , Análise Espectral Raman
14.
Transl Psychiatry ; 12(1): 114, 2022 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-35318322

RESUMO

Autism spectrum disorder (ASD) is a neurodevelopmental disease featuring social interaction deficits and repetitive/stereotyped behaviours; the prevalence of this disorder has continuously increased. Progranulin (PGRN) is a neurotrophic factor that promotes neuronal survival and differentiation. However, there have not been sufficient studies investigating its effect in animal models of autism. This study investigated the effects of PGRN on autistic phenotypes in rats treated with valproic acid (VPA) and assessed the underlying molecular mechanisms. PGRN was significantly downregulated in the cerebellum at postnatal day 14 (PND14) and PND35 in VPA-exposed rats, which simultaneously showed defective social preference, increased repetitive behaviours, and uncoordinated movements. When human recombinant PGRN (r-PGRN) was injected into the cerebellum of newborn ASD model rats (PND10 and PND17), some of the behavioural defects were alleviated. r-PGRN supplementation also reduced cerebellar neuronal apoptosis and rescued synapse formation in ASD rats. Mechanistically, we confirmed that PGRN protects neurodevelopment via the PI3K/Akt/GSK-3ß pathway in the cerebellum of a rat ASD model. Moreover, we found that prosaposin (PSAP) promoted the internalisation and neurotrophic activity of PGRN. These results experimentally demonstrate the therapeutic effects of PGRN on a rat model of ASD for the first time and provide a novel therapeutic strategy for autism.


Assuntos
Transtorno do Espectro Autista , Ácido Valproico , Animais , Transtorno do Espectro Autista/induzido quimicamente , Transtorno do Espectro Autista/tratamento farmacológico , Cerebelo , Glicogênio Sintase Quinase 3 beta , Fosfatidilinositol 3-Quinases , Progranulinas/uso terapêutico , Proteínas Proto-Oncogênicas c-akt , Ratos , Ácido Valproico/efeitos adversos
15.
Biosci Rep ; 42(3)2022 03 31.
Artigo em Inglês | MEDLINE | ID: mdl-35302166

RESUMO

Adipose-derived stem cells (ADSCs) showed decreased cell viability and increased cell death under oxygen-glucose deprivation (OGD). Meanwhile, vital necroptotic proteins, including receptor-interacting protein kinase (RIP) 3 (RIP3) and mixed lineage kinase domain-like pseudokinase (MLKL), were expressed in the early stage. The present study aims to explore the effect of necroptosis inhibition on ADSCs. ADSCs were obtained from normal human subcutaneous fat and verified by multidirectional differentiation and flow cytometry. By applying cell counting kit-8 (CCK-8), calcein/propidium iodide (PI) staining and immunostaining, we determined the OGD treatment time of 4 h, a timepoint when the cells showed a significant decrease in viability and increased protein expression of RIP3, phosphorylated RIP3 (pRIP3) and phosphorylated MLKL (pMLKL). After pretreatment with the inhibitor of RIP3, necroptotic protein expression decreased under OGD conditions, and cell necrosis decreased. Transwell assays proved that cell migration ability was retained. Furthermore, the expression of the adipogenic transcription factor peroxisome proliferator-activated receptor γ (PPARγ) and quantitative analysis of Oil Red O staining increased in the inhibitor group. The expression of vascular endothelial growth factor-A (VEGFA) and fibroblast growth factor 2 (FGF2) and the migration test suggest that OGD increases the secretion of vascular factors, promotes the migration of human umbilical vein endothelial cells (HUVECs), and forms unstable neovascularization. ELISA revealed that inhibition of RIP3 increased the secretion of the anti-inflammatory factor, interleukin (IL)-10 (IL-10) and reduced the expression of the proinflammatory factor IL-1ß. Inhibition of RIP3 can reduce the death of ADSCs, retain their migration ability and adipogenic differentiation potential, reduce unstable neovascularization and inhibit the inflammatory response.


Assuntos
Glucose , Células-Tronco , Fator A de Crescimento do Endotélio Vascular , Adipogenia , Tecido Adiposo/citologia , Apoptose , Fator 2 de Crescimento de Fibroblastos , Glucose/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Inflamação , Oxigênio/farmacologia , Proteína Serina-Treonina Quinases de Interação com Receptores/antagonistas & inibidores , Células-Tronco/citologia
16.
Aesthet Surg J ; 42(6): NP407-NP415, 2022 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-35182422

RESUMO

BACKGROUND: External volume expander (EVE)-assisted autologous fat grafting is suitable for breast augmentation, but no large sample study in Asia has confirmed this method. OBJECTIVES: The authors reported their experience and outcomes in augmentation mammoplasty with EVE-assisted autologous fat grafting. METHODS: A retrospective study was conducted in 305 female patients who underwent augmentation mammoplasty with EVE-assisted fat grafting between September 2012 and December 2020. Doctors utilized Crisalix (Crisalix S.A., Lausanne, Switzerland) for 3-dimensional (3D) imaging acquisition to measure the increase in breast volume to evaluate doctor satisfaction. The Preoperative Satisfaction with Breast and BREAST-Q questionnaires were employed to assess patients' preoperative and postoperative satisfaction, respectively. RESULTS: The 305 female patients were aged 18 to 50 years (mean, 35.9 years). Among them, 68.52% were "very satisfied," 18.69% were "somewhat satisfied," 11.15% were "somewhat dissatisfied," and 1.64% were "very dissatisfied" based on BREAST-Q analysis, whereas 100% were dissatisfied according to the Preoperative Satisfaction with Breast questionnaire. Doctors employed Crisalix to measure the increase in breast volume to evaluate doctor satisfaction. The results showed 76.01% had an increase in breast volume of 150 to 250 mL or >250 mL and were "satisfied" and "very satisfied," respectively, 21.64% had an increase of 50 to 149 mL and were "somewhat satisfied," and 2.30% had an increase <50 mL and were "dissatisfied." There were no complications, such as obvious fat liquefaction, infection, or fat embolism. CONCLUSIONS: Augmentation mammoplasty with EVE-assisted fat grafting is effective and satisfying in China. Crisalix for 3D imaging acquisition is convenient and effective in measuring breast volume.


Assuntos
Tecido Adiposo , Mamoplastia , Tecido Adiposo/transplante , Mama/diagnóstico por imagem , Mama/cirurgia , Feminino , Humanos , Mamoplastia/métodos , Estudos Retrospectivos , Transplante Autólogo , Resultado do Tratamento
17.
J Leukoc Biol ; 112(4): 901-911, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35088475

RESUMO

Small cell lung cancer (SCLC) is characterized by a high relapse rate, drug tolerance, and limited treatment choices. Chimeric antigen receptor (CAR)-modified NK cells represent a promising immunotherapeutic modality for cancer treatment. However, their potential applications have not been explored in SCLC. Delta-like ligand 3 (DLL3) has been reported to be overexpressed in SCLC and may be a rational target for CAR NK immunotherapy. In this study, we developed DLL3-specific NK-92 cells and explored their potential in the treatment of SCLC. A coculture of DLL3+ SCLC cell lines with DLL3-CAR NK-92 cells exhibited significant in vitro cytotoxicity and cytokine production. DLL3-CAR NK-92 cells induced tumor regression in an H446-derived pulmonary metastasis tumor model under a good safety threshold. The potent antitumor activities of DLL3-CAR NK-92 cells were observed in subcutaneous tumor models of SCLC. Moreover, obvious tumor-infiltrated DLL3-CAR NK-92 cells were detected in DLL3+ SCLC xenografts. These findings indicate that DLL3-CAR NK-92 cells might be a potential strategy for the treatment of SCLC.


Assuntos
Neoplasias Pulmonares , Receptores de Antígenos Quiméricos , Carcinoma de Pequenas Células do Pulmão , Linhagem Celular Tumoral , Citocinas/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Ligantes , Neoplasias Pulmonares/tratamento farmacológico , Proteínas de Membrana/metabolismo , Recidiva Local de Neoplasia , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/metabolismo
18.
Anal Chim Acta ; 1183: 338981, 2021 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-34627510

RESUMO

An electrochemical assistance solid-phase microextraction (EA-SPME) was developed based on amino functionalized multi-walled carbon nanotube/polypyrrole (MWCNTs-NH2/PPy) composite coating. It was applied for the extraction of eight phenols in food contact material, including 2-chlorophenol, o-cresol, m-cresol, 2,4-dichlorophenol, 4-tert-butylphenol, 4-chlorophenol, 4-tertoctylphenol and alpha-naphthol. MWCNTs-NH2/PPy coating was characterized by scanning electron microscopy, transmission electron microscope, X-ray energy spectrometer, X-ray diffraction, Fourier transform infrared and thermogravimetric analysis. The adsorption mechanism of phenols on the composite coatings was investigated. The coating modified steel-wire as an extraction fiber has good electroconductibility, reproducibility and long service life. A determination method for the eight phenols was established by EA-SPME coupled with gas chromatography-flame ionization detection. Under the optimal experimental conditions (extraction temperature: 40 °C; extraction time: 30 min; stirring rate: 600 rpm; NaCl concentration: 0.15 g mL-1; desorption temperature: 250 °C and desorption time: 4 min), the detection linear range was 0.005-50 µg L-1 (R2>0.99), and the detection limit was 0.001-0.1 µg L-1 (S/N = 3). For the quintuple analysis of 50 µg L-1 phenols, the single fiber RSDs were 2.2-12.4%, and the fiber-to-fiber RSDs were 1.9-10.5%. The method was used to detect the migration quantity of the eight phenols from five canned packaging materials, which showed satisfactory recovery 87.3-118.9%.


Assuntos
Nanotubos de Carbono , Microextração em Fase Sólida , Fenóis , Polímeros , Pirróis , Reprodutibilidade dos Testes
19.
Int J Biol Sci ; 17(14): 3850-3861, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34671203

RESUMO

Background: The application of chimeric antigen receptor (CAR) NK cells in solid tumors is hindered by lack of tumor-specific targets and inefficient CAR NK cell efficacy. It has been reported that mesothelin (MSLN) may be an ideal immunotherapy target for gastric cancer. However, the feasibility of using anti-MSLN CAR NK cells to treat gastric cancer remains to be studied. Methods: MSLN expression in primary human gastric cancer, normal tissues and cell lines were detected. MSLN and CD19 targeted CAR NK-92 (MSLN- and CD19-CAR NK) cells were constructed, purified and verified. N87, MKN-28, AGS and Huh-7 cells expressing the GFP and luciferase genes were transduced. Cell- and patient-derived xenograft (PDX) were established via NSG mice. The ability of MSLN-CAR NK cells to kill MSLN-positive gastric cancer cells were evaluated in vitro and in vivo. Results: MSLN-CAR NK cells can specifically kill MSLN-positive gastric cancer cells (N87, MKN-28 and AGS), rather than MSLN negative cell (Huh-7), in vitro. Moreover, compared with parental NK-92 cells and CD19-CAR NK cells, stronger cytokine secretions were secreted in MSLN-CAR NK cells cocultured with N87, MKN-28 and AGS. Furthermore, MSLN-CAR NK cells can effectively eliminate gastric cancer cells in both subcutaneous and intraperitoneal tumor models. They could also significantly prolong the survival of intraperitoneally tumor-bearing mice. More importantly, the potent antitumor effect and considerable NK cell infiltration were observed in the patient-derived xenograft treated with MSLN-CAR NK cells, which further warranted the therapeutic effects of MSLN-CAR NK cells to treat gastric cancer. Conclusion: These results demonstrate that MSLN-CAR NK cells possess strong antitumor activity and represent a promising therapeutic approach to gastric cancer.


Assuntos
Imunoterapia/métodos , Células Matadoras Naturais/imunologia , Mesotelina/imunologia , Receptores de Antígenos Quiméricos/imunologia , Neoplasias Gástricas/terapia , Animais , Linhagem Celular Tumoral , Feminino , Perfilação da Expressão Gênica , Humanos , Mesotelina/genética , Camundongos , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Talanta ; 235: 122743, 2021 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-34517611

RESUMO

The analysis of contaminants in migration of food contact material (FCMs) is an urgent demand for food safety. In this study, melamine and formaldehyde in melamine kitchenware were selectively analyzed by surface-enhanced Raman scattering (SERS) via aptamer/derivatization-based membrane assembly. The membrane assembly was designed by simple filtration of Ag nanoparticles-decorated "stellate" silicon dioxide (SiO2/Ag) and composites of reduced graphene oxide and Ag nanoparticles (rGO/Ag) functioned with specific reagents. High selectivity can be realized by melamine aptamer and derivatization reagent of formaldehyde, respectively. The relative standard deviations (RSDs) of melamine and formaldehyde analysis for 11 replicate measurements, 14 consecutive days and 25 batches are less than 6.0 %, which shows excellent repeatability and reproducibility. After the method was validated, the limits of detection (LOD) for melamine and formaldehyde are 0.15 mg/L and 0.21 mg/L, respectively. The developed method was applied to determine the content of melamine and formaldehyde in migration of melamine kitchenware with low relative errors (less than 5.3 %) compared to chromatographic results. The recoveries of melamine and formaldehyde for migrations of melamine kitchenware are 91.2-110.0 % and 94.0-106.0 % with RSDs in range of 1.8-8.3 % and 4.7-9.1 %, respectively. The method proposed a new concept of convenient, portable and reliable strategy for analysis of melamine and formaldehyde in migration from FCMs.


Assuntos
Nanopartículas Metálicas , Análise Espectral Raman , Formaldeído , Reprodutibilidade dos Testes , Dióxido de Silício , Prata , Triazinas
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA