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1.
J Hazard Mater ; 435: 129018, 2022 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-35504133

RESUMO

Crude oil spills have caused catastrophic damage to marine ecosystems and become a global challenge. Although various liquid absorption materials have been developed, manual operations such as pumping and electric heating are still required in the face of highly viscous spilled oils. Efficient and autonomous crude oil spill cleanup methods are urgently needed. Here, inspired by the unidirectional microstructure of tree xylem, we report a sponge (SPC-Sponge), which combines superhydrophobic property and aligned porous structures, prepared from a ternary suspension (hydrophobic silica nanoparticles, polyurethane, and cellulose nanofibers) by single-step directional freeze casting. SPC-Sponge not only effectively overcome the limitations of traditional synthetic modification methods on the shape and size of porous sponge materials, but also has excellent oil-water selection function, liquid absorption speed, and liquid absorption capacity compared with common porous materials. Moreover, the sponge can self-absorb highly viscous crude oil of around 80,000 mPa‧s on seawater without external energy and human intervention. By adding multi-walled carbon nanotubes, the sponge can implement in-situ solar heating of crude oil, and the absorption speed is further improved. Given its unique structural design and superwetting property, this SPC-Sponge provides an efficient remediation approach for viscous oil spills.

2.
Clin Neuroradiol ; 2022 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-35543744

RESUMO

PURPOSE: This study sought to explore changes of brain dynamic functional network connectivity (dFNC) in adults with autism spectrum disorder (ASD) and investigate their relationship with clinical manifestations. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired from 78 adult ASD patients from autism brain imaging data exchange datasets, and 65 age-matched healthy controls subjects from the local community. Independent component analysis was conducted to evaluate dFNC patterns on the basis of 13 independent components (ICs) within 11 resting-state networks (RSN), namely, auditory network (AUDN), basal ganglia network (BGN), language network (LN), sensorimotor network (SMN), precuneus network (PUCN), salience network (SN), visuospatial network (VSN), dorsal default mode network (dDMN), high visual network (hVIS), primary visual network (pVIS), ventral default mode network (vDMN). Fraction time, mean dwell time, number of transitions, and RSN connectivity were calculated for group comparisons. Correlation analyses were performed between abnormal metrics and autism diagnostic observation schedule (ADOS) scores. RESULTS: Compared with controls, ASD patients had higher fraction time and mean dwell time in state 2 (P = 0.017, P = 0.014). Reduced dFNC was found in the SMN with PUCN, SMN with hVIS, and increased dFNC was observed in the dDMN with SN in state 2 in the ASD group. Fraction time and mean dwell time was positively correlated with stereotyped behavior scores of ADOS. CONCLUSION: The findings demonstrated the importance of evaluating transient alterations in specific neural networks of adult ASD patients. The abnormal metrics and connectivity may be related to symptoms such as stereotyped behavior.

3.
Artigo em Inglês | MEDLINE | ID: mdl-35567627

RESUMO

INTRODUCTION: Distinct physiological states arise from complex interactions among the various organs present in the human body. PET is a non-invasive modality with numerous successful applications in oncology, neurology, and cardiology. However, while PET imaging has been applied extensively in detecting focal lesions or diseases, its potential in detecting systemic abnormalities is seldom explored, mostly because total-body imaging was not possible until recently. METHODS: In this context, the present study proposes a framework capable of constructing an individual metabolic abnormality network using a subject's whole-body 18F-FDG SUV image and a normal control database. The developed framework was evaluated in the patients with lung cancer, the one discharged after suffering from Covid-19 disease, and the one that had gastrointestinal bleeding with the underlying cause unknown. RESULTS: The framework could successfully capture the deviation of these patients from healthy subjects at the level of both system and organ. The strength of the altered network edges revealed the abnormal metabolic connection between organs. The overall deviation of the network nodes was observed to be highly correlated to the organ SUV measures. Therefore, the molecular connectivity of glucose metabolism was characterized at a single subject level. CONCLUSION: The proposed framework represents a significant step toward the use of PET imaging for identifying metabolic dysfunction from a systemic perspective. A better understanding of the underlying biological mechanisms and the physiological interpretation of the interregional connections identified in the present study warrant further research.

4.
Med Phys ; 2022 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-35394071

RESUMO

PURPOSE: This study explored the feasibility of reducing the scan time of Patlak parametric imaging on the uEXPLORER. METHODS: A total of 65 patients (27 females and 38 males, age 56.1 ± 10.4) were recruited in this study. 18F fluorodeoxyglucose was injected, and its dose was adjusted by body weight (4.07 MBq/kg). Total-body dynamic scanning was performed on the uEXPLORER total-body Positron emission tomography/computed tomography (CT) scanner with a total scan time of 60 min from the injection. The image derived input function (IDIF) was obtained from the aortic arch. The voxelwise Patlak analysis was applied to generate the Ki images designated as GIDIF with different acquisition times (20-60, 30-60, 40-60, and 44-60 min). The population-based input function (PBIF) was constructed from the mean value of the IDIF from the population, and Ki images designated as GPBIF were generated using the PBIF. Nonlocalmeans (NLM) denoising was applied to the generated images to get two extra groups of (NLM-designated) images: GIDIF+NLM and GPBIF+NLM . Two radiologists evaluated the overall image quality, noise, and lesion detectability of the Ki images from different groups. The 20-60 min scans in GIDIF were selected as the gold standard for each patient. We determined that image quality is at sufficient level if all the lesions can be recognized and meet the clinical criteria. Ki values in muscle and lesion were compared across different groups to evaluate the quantitative accuracy. RESULTS: The overall image quality, image noise, and lesion conspicuity were significantly better in long time series than short time series in all four groups (all p < 0.001). The Ki images in the GIDIF and GPBIF groups generated from 30-min scans showed diagnostic value equivalent to the 40-min scans of GIDIF . While the image quality of the 16-min scans was poor, all lesions could still be detected. No significant difference was found between Ki values estimated with GIDIF and GPBIF in muscle and lesion regions (all p > 0.5). After applying the NLM filter, the coefficient of variation could be reduced on the order of (1%, 15%, 19%, and 37%) and (110%, 125%, 94%, and 69%) with four acquisition time schemes for lesion and muscle. The reduction percentage did not have a substantial difference in IDIF and PBIF group. The Ki images in the GIDIF+NLM and GPBIF+NLM groups generated from the 20-min acquisitions showed acceptable quality. All lesions could be found on the NLM processed images of the 16-min scans. No significant difference was found between Ki values produced with GIDIF+NLM and GPBIF+NLM in muscle and lesion regions(all p > 0.7). CONCLUSIONS: The Ki images generated by the PBIF-based Patlak model using a 20-min dynamic scan with the NLM filter achieved a similar diagnostic efficiency to images with GIDIF from 40-min dynamic data, and there is no significant difference between Ki images generated using IDIF or PBIF (p > 0.5).

5.
Nutr Diabetes ; 12(1): 25, 2022 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-35468888

RESUMO

BACKGROUND: Inappropriate weight gain may increase the risk of gestational diabetes mellitus (GDM). However, the relationship between pre-pregnancy body mass index (BMI), weight gain, and GDM has not been precisely quantified. This study aimed to explore whether gestational weight gain played a mediating role between pre-pregnancy BMI and GDM and whether the mediating effect was sex specific. METHODS: This study established a population-based observational cohort to assess weight gain in pregnant women. Mediation analyses were performed to quantify whether weight gain mediated the association between pre-pregnancy BMI and GDM. RESULTS: A total of 67,777 pregnant women were included in the final analysis, among whom 6751 (10.0%) were diagnosed with GDM. We verified that both pre-pregnancy BMI and weight gain were associated with GDM, and that BMI negatively contributed to weight gain. We also found that weight gain had a significant mediating effect on the relationship between pre-pregnancy BMI and GDM (Za × Zb confidence intervals [CIs] 0.00234-0.00618). Furthermore, the effect was sex-specific, in that it was only significant in overweight women carrying female fetuses (Za × Zb CIs 0.00422-0.01977), but not male fetuses (Za × Zb CIs -0.00085 to 0.01236). CONCLUSIONS: Weight gain during pregnancy had a fetal sex-specific mediating effect between pre-pregnancy BMI and GDM.


Assuntos
Diabetes Gestacional , Ganho de Peso na Gestação , Índice de Massa Corporal , Feminino , Humanos , Masculino , Sobrepeso/complicações , Gravidez , Ganho de Peso
6.
Front Immunol ; 13: 824188, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35444652

RESUMO

Exosomes are small extracellular vesicles that are secreted by almost all types of cells and exist in almost all extracellular spaces. As an important mediator of intercellular communication, exosomes encapsulate the miRNA, lncRNA, cirRNA, mRNA, cytokine, enzyme, lipid, and other components from the cytoplasm into its closed single membrane structure and transfer them to recipient units in an autocrine, paracrine, or endocrine manner. Hypoxia is a state of low oxygen tension and is involved in many pathological processes. Hypoxia influences the size, quantity, and expression of exosome cargos. Exosomes derived from hypoxic tumor cells transfer genetics, proteins, and lipids to the recipient units to exert pleiotropic effects. Different donor cells produce different cargo contents, target different recipient units and lead to different biological effects. Hypoxic exosomes derived from tumor cells uptaken by normoxic tumor cells lead to promoted proliferation, migration, and invasion; uptaken by extracellular space or liver lead to promoted metastasis; uptaken by endothelial cells lead to promoted angiogenesis; uptaken by immune cells lead to promoted macrophage polarization and changed tumor immune microenvironment. In addition to various types of tumors, hypoxic exosomes also participate in the development of diseases in the cardiovascular system, neuron system, respiratory system, hematology system, endocrine system, urinary system, reproduction system, and skeletomuscular system. Understanding the special characteristics of hypoxic exosomes provide new insight into elaborating the pathogenesis of hypoxia related disease. This review summarizes hypoxia induced cargo changes and the biological effects of hypoxic exosomes in tumors and non-malignant diseases in different systems.


Assuntos
Exossomos , Neoplasias , Comunicação Celular , Células Endoteliais/metabolismo , Exossomos/metabolismo , Humanos , Hipóxia/metabolismo , Neoplasias/metabolismo , Microambiente Tumoral
7.
Front Aging Neurosci ; 14: 785495, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35450057

RESUMO

Introduction: 11C-labeled Pittsburgh compound B (11C-PiB) PET imaging can provide information for the diagnosis of Alzheimer's disease (AD) by quantifying the binding of PiB to ß-amyloid deposition in the brain. Quantification index, such as standardized uptake value ratio (SUVR) and distribution volume ratio (DVR), has been exploited to effectively distinguish between healthy and subjects with AD. However, these measures require a long wait/scan time, as well as the selection of an optimal reference region. In this study, we propose an alternate measure named amyloid quantification index (AQI), which can be obtained with the first 30-min scan without the selection of the reference region. Methods: 11C-labeled Pittsburgh compound B PET scan data were obtained from the public dataset "OASIS-3". A total of 60 mild subjects with AD and 60 healthy controls were included, with 50 used for training and 10 used for testing in each group. The proposed measure AQI combines information of clearance rate and mid-phase PIB retention in featured brain regions from the first 30-min scan. For each subject in the training set, AQI, SUVR, and DVR were calculated and used for classification by the logistic regression classifier. The receiver operating characteristic (ROC) analysis was performed to evaluate the performance of these measures. Accuracy, sensitivity, and specificity were reported. The Kruskal-Wallis test and effect size were also performed and evaluated for all measures. Then, the performance of three measures was further validated on the testing set using the same method. The correlations between these measures and clinical MMSE and CDR-SOB scores were analyzed. Results: The Kruskal-Wallis test suggested that AQI, SUVR, and DVR can all differentiate between the healthy and subjects with mild AD (p < 0.001). For the training set, ROC analysis showed that AQI achieved the best classification performance with an accuracy rate of 0.93, higher than 0.88 for SUVR and 0.89 for DVR. The effect size of AQI, SUVR, and DVR were 2.35, 2.12, and 2.06, respectively, indicating that AQI was the most effective among these measures. For the testing set, all three measures achieved less superior performance, while AQI still performed the best with the highest accuracy of 0.85. Some false-negative cases with below-threshold SUVR and DVR values were correctly identified using AQI. All three measures showed significant and comparable correlations with clinical scores (p < 0.01). Conclusion: Amyloid quantification index combines early-phase kinetic information and a certain degree of ß-amyloid deposition, and can provide a better differentiating performance using the data from the first 30-min dynamic scan. Moreover, it was shown that clinically indistinguishable AD cases regarding PiB retention potentially can be correctly identified.

8.
Diagn Pathol ; 17(1): 30, 2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35172862

RESUMO

BACKGROUND: Pulmonary enteric adenocarcinoma (PEAC) has distinctive clinical outcomes, radiographic, pathological and molecular characteristics. The prognosis of patients with PEAC was poor. However, molecular profiles and therapeutic biomarkers of PEAC remain elusive. METHODS: In the present study, the hospitalized patients with PEAC admitted to Tongji Hospital in Wuhan from January 1, 2014 to November 20, 2020 were retrospectively enrolled and followed until December 10, 2020. Comprehensive genomic profiling of tumor tissue from the PEAC patients were performed and compared with lung adenocarcinoma, colorectal cancer and metastatic colorectal carcinoma. Tumor immune microenvironment analysis were evaluated. RESULTS: There were 10 patients with PEAC enrolled. 70% of patients were male and the median age of onset was 63 years (interquartile range, 55-72). There were six early-stage patients (Stage IA to IIB) and four stage IV patients. Molecular analysis revealed the most common gene mutations included TP53 (57%, 4/7) and KRAS (57%, 4/7) mutations. There were 40% mutations occurred in genes encoding receptor tyrosine kinases (RTKs). 100% of patients (8/8) were microsatellite stability (MSS). The median level of TMB was 6.0 (interquartile range, 4.5-7.0) mutations/Mb. Three of 10 patients showed low PD-L1 expression (tumor proportion score < 10%) and the others were PD-L1 negative. A small subset of CD8+, CD3+, CD68+ T cells were observed and were mainly distributed in the cancer stroma. CONCLUSION: This study demonstrated that PEAC was characterized by low-frequency RTK gene mutation, high KRAS mutation, low PD-L1 expression, low TMB, and low CD8+ T cells infiltration.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/genética , Antígeno B7-H1/análise , Antígeno B7-H1/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Perfil Genético , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Retrospectivos , Microambiente Tumoral/genética
9.
Plant Signal Behav ; 17(1): 2035126, 2022 12 31.
Artigo em Inglês | MEDLINE | ID: mdl-35184695

RESUMO

Bacterial leaf blight caused by Xanthomonas oryzae pv. oryzae (Xoo) has always been considered to be one of the most severe worldwide diseases in rice. Xoo strains usually use the highly conserved type III secretion system (T3SS) to deliver virulence effectors into rice cells and further suppress the host's immunity. Previous studies reported that different Xanthomonas outer protein (Xop) effectors include XopZ from one strain appear to share functional redundancies on suppressing rice PAMP-triggered immunity (PTI). But only xopZ, except other xop genes, could significantly impaire Xoo virulence when individually deleting in PXO99 strains. Thus, the XopZ effector should not only suppress rice PTI pathway, but also has other unknown indispensable pathological functions in PXO99-rice interactions. Here, we also found that ∆xopZ mutant strains displayed lower virulence on Nipponbare leaves compared with PXO99 strains. We identified an oxysterol-binding related protein, ORP1C, as a XopZ-interacting protein in rice. Further studies found that rice ORP1C preliminarily played a positive role in regulating the resistance to PXO99 strains, and XopZ-ORP1C interactions cooperated to regulate the compatible interactions of PXO99-Nipponbare rice. The reactive oxygen species (ROS) burst and PTI marker gene expression data indicated that ORP1C were not directly relevant to the PTI pathway in rice. The deeper mechanisms underlying XopZ-ORP1C interaction and how XopZ and ORP1C cooperate for regulating the PXO99-rice interactions require further exploration.


Assuntos
Oryza , Xanthomonas , Oryza/genética , Padrões Moleculares Associados a Patógenos , Virulência
10.
Biol Res ; 55(1): 5, 2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35115050

RESUMO

BACKGROUND: G protein coupled receptor kinase 2 (GRK2) has been demonstrated to play a crucial role in the development of chronic pain. Acupuncture is an alternative therapy widely used for pain management. In this study, we investigated the role of spinal neuronal GRK2 in electroacupuncture (EA) analgesia. METHODS: The mice model of inflammatory pain was built by subcutaneous injection of Complete Freund's Adjuvant (CFA) into the plantar surface of the hind paws. The mechanical allodynia of mice was examined by von Frey test. The mice were subjected to EA treatment (BL60 and ST36 acupuncture points) for 1 week. Overexpression and downregulation of spinal neuronal GRK2 were achieved by intraspinal injection of adeno associated virus (AAV) containing neuron-specific promoters, and microglial activation and neuroinflammation were evaluated by real-time PCR. RESULTS: Intraplantar injection with CFA in mice induced the decrease of GRK2 and microglial activation along with neuroinflammation in spinal cord. EA treatment increased the spinal GRK2, reduced neuroinflammation, and significantly decreased CFA-induced mechanical allodynia. The effects of EA were markedly weakened by non-cell-specific downregulation of spinal GRK2. Further, intraspinal injection of AAV containing neuron-specific promoters specifically downregulated neuronal GRK2, and weakened the regulatory effect of EA on CFA-induced mechanical allodynia and microglial activation. Meanwhile, overexpression of spinal neuronal GRK2 decreased mechanical allodynia. All these indicated that the neuronal GRK2 mediated microglial activation and neuroinflammation, and subsequently contributed to CFA-induced inflammatory pain. CONCLUSION: The restoration of the spinal GRK2 and subsequent suppression of microglial activation and neuroinflammation might be an important mechanism for EA analgesia. Our findings further suggested that the spinal GRK2, especially neuronal GRK2, might be the potential target for EA analgesia and pain management, and we provided a new experimental basis for the EA treatment of pain.


Assuntos
Eletroacupuntura , Quinase 2 de Receptor Acoplado a Proteína G/fisiologia , Microglia/fisiologia , Manejo da Dor , Animais , Inflamação/induzido quimicamente , Inflamação/terapia , Camundongos , Neurônios , Dor/induzido quimicamente
11.
ACS Appl Mater Interfaces ; 14(9): 11789-11802, 2022 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-35195410

RESUMO

Efficient micron-sized droplet separation materials have become a new demand for environmental protection and economic development. However, existing separation methods are difficult to be effectively used for micron-sized water droplets surrounded by viscous oil, and common materials have difficulty maintaining hydrophilicity underoil. Here, inspired by the microstructure of tree xylem, we report a cellulose-polyurethane sponge (CP-Sponge) with wood-like pores and underoil superhydrophilicity using directional freeze-casting. The CP-Sponge has an excellent selective water absorption capacity underoil and compression resilience. This preparation strategy can flexibly control the sponge's dimensional morphology. The designed cylindrical CP-Sponge can be easily installed in the silicone tube of a peristaltic pump. During pump operation, with a simple absorption, compression, and recovery process, the CP-Sponge continuously and effectively removes micron-sized water from crude oil and lubricating oil, reducing residual water in the oil to less than 2 ppm. The absorption-saturated sponge can be dried to continue recycling. Eco-friendly, recyclable, and sustainable artificial porous sponges provide new ideas and inspiration for the practical application of deep dehydration of viscous oils.

12.
Int J Mol Med ; 49(3)2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35059734

RESUMO

Spliced X­box binding protein 1 (XBP1s) has been reported to participate in the pathogenesis of numerous types of cancer; however, whether XBP1s plays a role in lung cancer remains to be elucidated. In the present study, bioinformatics analysis was performed to determine the mRNA expression level of XBP1 in lung cancer and adjacent normal tissues. Gene Ontology terms, pathway enrichment and Pearson's correlation analysis were performed to investigate the possible mechanism involved. Western blot and reverse transcription­quantitative PCR were performed to quantify the protein and mRNA expression level of target proteins, respectively. Small interfering RNA or overexpression plasmid were used to knockdown or overexpress the expression level of XBP1s. EdU staining, colony formation, Cell Counting Kit­8, Transwell and wound healing assays, and flow cytometry were performed to detect the proliferation, colony forming ability, cell viability, migration and invasion ability, and the apoptosis rate. The results showed that the mRNA and protein expression level of XBP1 was higher in tumor tissues compared with that in adjacent normal tissues using data from the TIMER2.0, ONCOMINE and UALCAN online databases. In addition, the mRNA expression level of XBP1 was also associated with clinical features, including age, smoking habit, individual cancer stage and nodal metastasis status. In the in vitro experiments, the mRNA and protein expression level of XBP1s was increased in the A549 cell line compared with that in the human bronchial epithelial (HBE), H1299, PC9 and H460 cell lines. Hypoxia further increased the protein expression level of XBP1s in the A549 cell line. Knockdown of XBP1s expression in the A549 cell line resulted in decreased proliferation, colony formation, cell viability, migration and invasion, and increased apoptosis. By contrast, overexpressing XBP1s in the HBE cell line led to the opposite results. To investigate the mechanism involved, proteins associated with XBP1 were analyzed using the LinkedOmics database. Pathway enrichment revealed the MAPK pathway to be the possible XBP1 downstream target. Furthermore, Pearson's correlation and western blot analyses verified that phosphorylated (p)­JNK rather than p­ERK or p­p38 was the downstream effector of XBP1s. Phosphorylation of JNK was decreased when XBP1s expression was knocked down in the A549 cell line under normoxic and hypoxic conditions. Inhibiting p­JNK with SP600125 reversed the increased prosurvival effects caused by XBP1s overexpression. The results from the present study suggest that XBP1s/p­JNK function as a prosurvival factors in the A549 cell line and could be a potential target for the treatment of lung adenocarcinoma.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Proteína 1 de Ligação a X-Box , Adenocarcinoma de Pulmão/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Sistema de Sinalização das MAP Quinases , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo
13.
J Adv Res ; 35: 141-151, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-35003798

RESUMO

Introduction: Knee osteoarthritis (KOA) showed synovial fibrosis and hyperalgesia, although the correlation between the two is unclear. Besides, the specific changes of sensory innervation in animal models are still controversial, which makes it difficult to choose the modeling methods for KOA pain research. Objectives: Study the characteristics of sensory innervation within three commonly used KOA rat models and the correlation between synovial fibrosis and hyperalgesia. Methods: KOA models were induced by destabilization of medial meniscus (DMM), anterior cruciate ligament transection (ACLT), and monoiodoacetate (MIA), respectively. Mechanical, cold and thermal withdrawal threshold (MWT, CWT and TWT) were measured. The harvested tissues were used for pathological sections, immunofluorescence and quantitative analysis. Results: KOA synovium showed more type I collagen deposition, increased expression of CD31, VEGF and TGF-ß. These changes were most pronounced in surgical models, with DMM presenting the most prominent at Day 14 and ACLT at Day 28. Day 14, changes in mechanical hyperalgesia and cold hyperalgesia were most typical in DMM model and statistically different from MIA. There was a negative correlation between the percentage of type I collagen and MWT value (r = -0.88), as well as CWT value (r = -0.95). DMM synovium showed more axonal staining, upregulated CGRP, TRPV1, NGF and Netrin1 compared with MIA. Above changes were also observed at Day 28, but ACLT replaced DMM as the most typical. In DRG, only the levels of CGRP and NGF were different among KOA models at Day 14, and the highest in DMM, which was statistically different compared with MIA. Conclusions: This study described the details of sensory innervation in different KOA model of rats, and the degree of synovial fibrosis was positively correlated with the pain sensitivity of KOA model rats. Additionally, surgical modeling especially ACLT method is more recommended for KOA pain research.


Assuntos
Osteoartrite do Joelho , Animais , Modelos Animais de Doenças , Fibrose , Hiperalgesia/patologia , Osteoartrite do Joelho/patologia , Ratos , Membrana Sinovial/patologia
14.
Respir Res ; 23(1): 6, 2022 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-35016680

RESUMO

BACKGROUND: Hypoxic pulmonary hypertension (HPH) is a chronic progressive advanced disorder pathologically characterized by pulmonary vascular remodeling. Notch4 as a cell surface receptor is critical for vascular development. However, little is known about the role and mechanism of Notch4 in the development of hypoxic vascular remodeling. METHODS: Lung tissue samples were collected to detect the expression of Notch4 from patients with HPH and matched controls. Human pulmonary artery smooth muscle cells (HPASMCs) were cultured in hypoxic and normoxic conditions. Real-time quantitative PCR and western blotting were used to examine the mRNA and protein levels of Notch4. HPASMCs were transfected with small interference RNA (siRNA) against Notch4 or Notch4 overexpression plasmid, respectively. Cell viability, cell proliferation, apoptosis, and migration were assessed using Cell Counting Kit-8, Edu, Annexin-V/PI, and Transwell assay. The interaction between Notch4 and ERK, JNK, P38 MAPK were analyzed by co-immunoprecipitation. Adeno-associated virus 1-mediated siRNA against Notch4 (AAV1-si-Notch4) was injected into the airways of hypoxic rats. Right ventricular systolic pressure (RVSP), right ventricular hypertrophy and pulmonary vascular remodeling were evaluated. RESULTS: In this study, we demonstrate that Notch4 is highly expressed in the media of pulmonary vascular and is upregulated in lung tissues from patients with HPH and HPH rats compared with control groups. In vitro, hypoxia induces the high expression of Delta-4 and Notch4 in HPASMCs. The increased expression of Notch4 promotes HPASMCs proliferation and migration and inhibits cells apoptosis via ERK, JNK, P38 signaling pathways. Furthermore, co-immunoprecipitation result elucidates the interaction between Notch4 and ERK/JNK/P38. In vivo, silencing Notch4 partly abolished the increase in RVSP and pulmonary vascular remodeling caused by hypoxia in HPH rats. CONCLUSIONS: These findings reveal an important role of the Notch4-ERK/JNK/P38 MAPK axis in hypoxic pulmonary remodeling and provide a potential therapeutic target for patients with HPH.


Assuntos
Regulação da Expressão Gênica , Hipertensão Pulmonar/genética , Hipóxia/complicações , Miócitos de Músculo Liso/metabolismo , Receptor Notch4/genética , Remodelação Vascular/genética , Proteínas Quinases p38 Ativadas por Mitógeno/genética , Animais , Apoptose , Proliferação de Células , Células Cultivadas , Modelos Animais de Doenças , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/patologia , Hipóxia/genética , Hipóxia/metabolismo , Sistema de Sinalização das MAP Quinases , Masculino , Miócitos de Músculo Liso/patologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia , Artéria Pulmonar/fisiopatologia , Ratos , Ratos Sprague-Dawley , Receptor Notch4/biossíntese , Transdução de Sinais , Regulação para Cima , Proteínas Quinases p38 Ativadas por Mitógeno/biossíntese
15.
Biochem Biophys Res Commun ; 590: 163-168, 2022 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-34979317

RESUMO

Liquid-phase electron microscopy is highly desirable for observing biological samples in their native liquid state at high resolution. We developed liquid imaging approaches for biological cells using scanning electron microscopy. Novel approaches included scanning transmission electron imaging using a liquid-cell apparatus (LC-STEM), as well as correlative cathodoluminescence and electron microscopy (CCLEM) imaging. LC-STEM enabled imaging at a ∼2 nm resolution and excellent contrast for the precise recognition of localization, distribution, and configuration of individually labeled membrane proteins on the native cells in solution. CCLEM improved the resolution of fluorescent images down to 10 nm. Liquid SEM technologies will bring unique and wide applications to the study of the structure and function of cells and membrane proteins in their near-native states at the monomolecular level.


Assuntos
Proteínas de Membrana/ultraestrutura , Microscopia Eletrônica de Varredura , Linhagem Celular Tumoral , Receptores ErbB/ultraestrutura , Fluorescência , Humanos
16.
Anesth Analg ; 134(1): 204-215, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34652301

RESUMO

BACKGROUND: The main symptoms of chemotherapy-induced peripheral neuropathy (CIPN) include pain and numbness. Neuronal G protein-coupled receptor kinase 2 (GRK2) plays an important role in various pain models. Cisplatin treatment can induce the activation of proinflammatory microglia in spinal cord. The purpose of this study was to investigate the role of spinal neuronal GRK2 in cisplatin-induced CIPN and in the prevention of CIPN by electroacupuncture (EA). METHODS: The pain and sensory deficit behaviors of mice were examined by von Frey test and adhesive removal test. The expression of neuronal GRK2 in the spinal cord is regulated by intraspinal injection of adeno-associated virus (AAV) containing neuron-specific promoters. The protein levels of GRK2, triggering receptor expressed on myeloid cells 2 (TREM2), and DNAX-activating protein of 12 kDa (DAP12) in spinal dorsal horn were detected by Western blot, the density of intraepidermal nerve fibers (IENFs) was detected by immunofluorescence, and microglia activation were evaluated by real-time polymerase chain reaction (PCR). RESULTS: In this study, cisplatin treatment led to the decrease of GRK2 expression in the dorsal horn of spinal cord. Overexpression of neuronal GRK2 in spinal cord by intraspinal injection of an AAV vector expressing GRK2 with human synapsin (hSyn) promotor significantly inhibited the loss of IENFs and alleviated the mechanical pain and sensory deficits induced by cisplatin. Real-time PCR analysis showed that the overexpression of neuronal GRK2 significantly inhibited the messenger RNA (mRNA) upregulation of proinflammatory cytokine interleukin (IL)-1ß, IL-6, inducible nitric oxide synthase (iNOS), and M1 microglia marker cluster of differentiation (CD)16 induced by cisplatin. Furthermore, the TREM2 and DAP12, which has been demonstrated to play a role in microglia activation and in the development of CIPN, were also downregulated by overexpression of neuronal GRK2 in this study. Interestingly, preventive treatment with EA completely mimics the effect of overexpression of neuronal GRK2 in the spinal cord in this mouse model of cisplatin-induced CIPN. EA increased GRK2 level in spinal dorsal horn after cisplatin treatment. Intraspinal injection of AAV vector specifically downregulated neuronal GRK2, completely reversed the regulatory effect of EA on CIPN and microglia activation. All these indicated that the neuronal GRK2 mediated microglial activation contributed to the process of CIPN. CONCLUSIONS: Neuronal GRK2 in the spinal cord contributed to the preventive effect of EA on CIPN. The neuronal GRK2 may be a potential target for CIPN intervention.


Assuntos
Cisplatino , Eletroacupuntura , Quinase 2 de Receptor Acoplado a Proteína G/genética , Doenças do Sistema Nervoso Periférico/induzido quimicamente , Medula Espinal/patologia , Animais , Comportamento Animal , Dependovirus , Humanos , Hiperalgesia/metabolismo , Inflamação , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Fibras Nervosas , Neuralgia/metabolismo , Neurônios/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Dor , Corno Dorsal da Medula Espinal/metabolismo , Fatores de Tempo
17.
Chemosphere ; 291(Pt 1): 132764, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34752836

RESUMO

Numerous studies have been investigated the toxic effects of silver nanoparticle (Ag-NPs) on algae; however, little attention has been paid to the defense pathways of algae cells to Ag-NPs. In the study, Chlamydomonas reinhardtii (C. reinhardtii) was selected as a model organism to investigate the defense mechanisms to Ag-NPs exposure. The results showed that exopolysaccharide and protein in bound-extracellular polymeric substances significantly increased under Ag-NPs stress. These metal-binding groups including C-O-C (exopolysaccharide), CH3/CH2 (proteins), O-H/N-H (hydroxyl group) and C-H (alkyl groups) played a key role in extracellular biosorption. The internalized or strongly bound Ag (1.90%-17.45% of total contents) was higher than the loosely surface biosorption (0.31%-1.79%). The accumulation of glutathione disulfide (GSSG), together with the decline of reduced glutathione/GSSG (GSH/GSSG) ratio in C. reinhardtii cells, indicated a significant oxidative stress caused by exposure of Ag-NPs. The increasing phytochelatin accompanied with the decreasing GSH level indicated a critical role to intracellular detoxification of Ag. Furthermore, upregulation of antioxidant genes (MSOD, QTOX2, CAT1, GPX2, APX and VTE3) can cope with oxidative stress of Ag-NPs or Ag+. The up-regulation of ascorbate peroxidase (APX) and glutathione peroxidase (GPX2) genes and the reduction in GSH contents showed that the toxicity of Ag-NPs could be mediated by an intracellular ascorbate-GSH defense pathway. These findings can provide valuable information on ecotoxicity of Ag-NPs, potential bioremediation and adaptation capabilities of algal cells to Ag-NPs.


Assuntos
Chlamydomonas reinhardtii , Nanopartículas Metálicas , Antioxidantes , Chlamydomonas reinhardtii/genética , Mecanismos de Defesa , Nanopartículas Metálicas/toxicidade , Estresse Oxidativo , Prata/toxicidade
18.
Front Plant Sci ; 13: 849483, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35498706

RESUMO

Soil microorganisms are the key driver of the geochemical cycle in forest ecosystem. Changes in litter and roots can affect soil microbial activities and nutrient cycling; however, the impact of this change on soil microbial community composition and function remain unclear. Here, we explored the effects of litter and root manipulations [control (CK), doubled litter input (DL), litter removal (NL), root exclusion (NR), and a combination of litter removal and root exclusion (NI)] on soil bacterial and fungal communities and functional groups during a 2-year field experiment, using illumina HiSeq sequencing coupled with the function prediction platform of PICRUSt and FUNGuild. Our results showed that litter and root removal decreased the diversity of soil bacteria and fungi (AEC, Shannon, and Chao1). The bacterial communities under different treatments were dominated by the phyla Proteobacteria, Acidobacteria, and Actinomycetes, and NL and NR reduced the relative abundance of the first two phyla. For the fungal communities, Basidiomycetes, Ascomycota, and Mortierellomycota were the dominant phyla. DL increased the relative abundance of Basidiomycetes, while NL and NR decreased the relative abundance of Ascomycota. We also found that litter and root manipulations altered the functional groups related to the metabolism of cofactors and vitamins, lipid metabolism, biosynthesis of other secondary metabolites, environmental adaptation, cell growth, and death. The functional groups including ectomycorrhizal, ectomycorrhizal-orchid mycorrhizal root-associated biotrophs and soil saprotrophs in the fungal community were also different among the different treatments. Soil organic carbon (SOC), pH, and soil water content are important factors driving changes in bacterial and fungal communities, respectively. Our results demonstrate that the changes in plant detritus altered the soil microbial community structure and function by affecting soil physicochemical factors, which provides important data for understanding the material cycle of forest ecosystems under global change.

19.
J Cell Physiol ; 237(3): 1948-1963, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34964131

RESUMO

Hypoxic pulmonary hypertension (HPH) is characterized by elevated pulmonary artery resistance and vascular remodeling. Endoplasmic reticulum stress (ERS) is reported to be involved in HPH, but the underlying mechanisms remain uncertain. We found that Xbp1s, a potent transcription factor during ERS, was elevated in hypoxic-cultured rat PASMCs and lung tissues from HPH rats. Our in vitro experiments demonstrated that overexpressing Xbp1s can promote proliferation, cell viability, and migration and inhibit the apoptosis of PASMCs, while silencing Xbp1s led to the opposite. Through data-independent acquisition (DIA) mass spectrometry, we identified extensive proteomic alterations regulated by hypoxia and Xbp1s. Further validation revealed that p-JNK, rather than p-ERK or p-p38, was the downstream effector of Xbp1s. p-JNK inhibition reversed the biological effects of Xbp1s overexpression in vitro. In the animal HPH model, rats were randomly assigned to five groups: normoxia, hypoxia, hypoxia+AAV-CTL (control), hypoxia+AAV-Xbp1s (prevention), and hypoxia+AAV-Xbp1s (therapy). Adeno-associated virus (AAV) serotype 1-mediated Xbp1s knockdown in the prevention and therapy groups significantly reduced right ventricular systolic pressure, total pulmonary resistance, right ventricular hypertrophy, and the medial wall thickness of muscularized distal pulmonary arterioles; AAV-Xbp1s also decreased proliferating cell nuclear antigen expression and increased apoptosis in pulmonary arterioles. Collectively, our findings demonstrated that the Xbp1s-p-JNK pathway is important in hypoxic vascular remodeling and that targeting this pathway could be an effective strategy to prevent and alleviate HPH development.


Assuntos
Hipertensão Pulmonar , Sistema de Sinalização das MAP Quinases , Proteína 1 de Ligação a X-Box , Animais , Proliferação de Células/genética , Modelos Animais de Doenças , Hipertensão Pulmonar/metabolismo , Hipóxia/metabolismo , Miócitos de Músculo Liso/metabolismo , Proteômica , Artéria Pulmonar/metabolismo , Ratos , Ratos Sprague-Dawley , Remodelação Vascular , Proteína 1 de Ligação a X-Box/genética , Proteína 1 de Ligação a X-Box/metabolismo
20.
Mediators Inflamm ; 2021: 4736670, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34876884

RESUMO

Synovitis is the primary driving factor for the occurrence and development of knee osteoarthritis (KOA) and fibroblast-like synoviocytes (FLSs) and plays a crucial role during this process. Our previous works revealed that transient receptor potential ankyrin 1 (TRPA1) ion channels mediate the amplification of KOA synovitis. In recent years, essential oils have been proved to have blocking effect on transient receptor potential channels. Meanwhile, the therapeutic effect of Sanse Powder on KOA synovitis has been confirmed in clinical trials and basic studies; although, the mechanism remains unclear. In the present study, Sanse Powder essential oil nanoemulsion (SP-NEs) was prepared, and then chemical composition, physicochemical properties, and stability were investigated. Besides, both in MIA-induced KOA rats and in LPS-stimulated FLSs, we investigated whether SP-NES could alleviate KOA synovitis by interfering with AMP-activated protein kinase- (AMPK-) mammalian target of rapamycin (mTOR), an energy sensing pathway proved to negatively regulate the TRPA1. Our research shows that the top three substances in SP-NEs were tumerone, delta-cadinene, and Ar-tumerone, which accounted for 51.62% of the total, and should be considered as the main pharmacodynamic ingredient. Less inflammatory cell infiltration and type I collagen deposition were found in the synovial tissue of KOA rats treated with SP-NEs, as well as the downregulated expressions of interleukin (IL)-1ß, IL-18, and TRPA1. Besides, SP-NEs increased the phosphorylation level of AMPK and decreased the phosphorylation level of mTOR in the KOA model, and SP-NEs also upregulated expressions of peroxisome proliferator-activated receptor-gamma (PPARγ) and PPARγ coactivator-1α and downstream signaling molecules of AMPK-mTOR in vivo and in vitro. To conclude, a kind of Chinese herbal medicine for external use which is effective in treating synovitis of KOA was extracted and prepared into essential oil nanoemulsion with stable properties in the present study. It may alleviate synovitis in experimental KOA through the negative regulation of TRPA1 by AMPK-mTOR signaling.


Assuntos
Proteínas Quinases Ativadas por AMP/fisiologia , Medicina Tradicional Chinesa , Óleos Voláteis/farmacologia , Osteoartrite do Joelho/tratamento farmacológico , Sinoviócitos/efeitos dos fármacos , Sinovite/tratamento farmacológico , Serina-Treonina Quinases TOR/farmacologia , Serina-Treonina Quinases TOR/fisiologia , Canal de Cátion TRPA1/fisiologia , Animais , Modelos Animais de Doenças , Emulsões , Masculino , Nanopartículas , Pós , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Sinoviócitos/fisiologia
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