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1.
Med Sci Monit ; 27: e929904, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34230447

RESUMO

BACKGROUND Since China has not yet constructed its own risk assessment model (RAM) for pregnancy-related venous thromboembolism (VTE), more and more hospitals use the RCOG RAM for VTE risk prediction. However, the RCOG RAM was established based on Western populations, and its applicability in China is still uncertain. Thus, we aimed to evaluate the validity of the RCOG RAM in predicting postpartum VTE in Chinese maternity. MATERIAL AND METHODS This retrospective case-control study was conducted at the International Peace Maternity and Child Health Hospital (IPMCHH) from June 2016 to June 2020. The VTE group consisted of 38 women with postpartum VTE. For each VTE patient, 4 women without VTE who gave birth on the same day were randomly selected as the control group (n=152). The receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA) were used to evaluate the discrimination, accuracy, and validity of the RCOG RAM. Univariable analysis and multivariable logistic regression analysis were used to identify other related factors for postpartum VTE. RESULTS Compared with the low-risk group, the risk of VTE was 9.75-fold greater in the intermediate-risk group, and 90.00-fold greater in the high-risk group. The area under curve (AUC) of the model was 0.828 (95% CI: 0.762-0.894), with a score of 2 as its best cut-off value, which exactly matched the criterion recommended by the RCOG guidelines for pharmacological thromboprophylaxis. The calibration curves and DCA of the model also showed good accuracy. In addition to the factors included in the RCOG RAM, glucocorticoid therapy during pregnancy (adjusted OR=6.72, 95% CI: 1.56-28.91) and previous use of IUD (adjusted OR=7.11, 95% CI: 1.45-34.93) were associated with increased risk of postpartum VTE. CONCLUSIONS The RCOG RAM was found to be effective in predicting postpartum VTE, and has certain guiding significance for postpartum thromboprophylaxis in China.

2.
Artigo em Inglês | MEDLINE | ID: mdl-34233850

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease and its advanced stage, nonalcoholic steatohepatitis (NASH), are the major cause of hepatocellular carcinoma (HCC) and other end-stage liver disease. However, the potential mechanism and therapeutic strategies have not been clarified. This study aimed to identify potential roles of miRNA/mRNA axis in the pathogenesis and drug combinations in the treatment of NASH. METHODS: Microarray GSE59045 and GSE48452 were downloaded from the Gene Expression Omnibus and analyzed using R. Then we obtained differentially expressed genes (DE-genes). DAVID database was used for Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment pathway analysis. Protein-protein interaction (PPI) networks were used for the identification of hub genes. We found upstream regulators of hub genes using miRTarBase. The expression and correlation of key miRNA and its targets were detected by qPCR. Drug Pair Seeker was employed to predict drug combinations against NASH. The expression of miRNA and hub genes in HCC was identified in the Cancer Genome Atlas database and Human Protein Atlas database. RESULTS: Ninety-four DE-genes were accessed. GO and KEGG analysis showed that these predicted genes were linked to lipid metabolism. Eleven genes were identified as hub genes in PPI networks, and they were highly expressed in cells with vigorous lipid metabolism. hsa-miR-335-5p was the upstream regulator of 9 genes in the 11 hub genes, and it was identified as a key miRNA. The hub genes were highly expressed in NASH models, while hsa-miR-335-5p was lowly expressed. The correlation of miRNA-mRNA was established by qPCR. Functional verification indicated that hsa-miR-335-5p had inhibitory effect on the development of NASH. Finally, drug combinations were predicted and the expression of miRNA and hub genes in HCC was identified. CONCLUSIONS: In the study, potential miRNA-mRNA pathways related to NASH were identified. Targeting these pathways may be novel strategies against NASH.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34255627

RESUMO

This paper proposes an innovative viscosity sensor based on the thickness-shear vibration of an SC-cut quartz resonator. The thickness-shear mode is firstly analyzed and further studied with fluid-structure interaction between the resonator and the viscous fluid loading. The characteristic equation is derived based on the 3D linear piezoelectric equations and solved for sensitivity analysis. Then laboratory experiment is carried out to validate the theory. To conduct the viscosity measurement, the SC-cut quartz resonator is integrated with a U-tube test fixture, which is designed and fabricated for sensor housing to avoid the influence of the mass of the fluid. The resonator is tested with various viscosities by tuning the ratio of glycerol/water mixture. Experiment results show consistency with the analytical solution, which together present an improved sensitivity of viscosity measurement by using SC-cut quartz resonator comparing to other resonator-based viscosity sensors. The proposed viscosity sensor is sensitive, accurate, and portable, and therefore can be applied to real-time, on-site measurement or sampling of fluidic samples.

4.
J Healthc Eng ; 2021: 6974225, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257854

RESUMO

Prostatic cancer (PCa) is a prevalent form of malignancy based on its high associated levels of mortality and morbidity across the world. MicroRNAs (miRNAs) are significant in the advancement of prostatic cancer. The current study is aimed at exploring the potential roles of miR-373 in PCa. In turn, the study conducted a qRT-PCR test to determine the levels of mRNA. A western blot test was also executed in determining the protein level. The processes of transwell assay and wound healing were integrated in the detection of the potential for PCa cells to invade and migrate. The integration of dual luciferase reporter assay is critical in determining the levels of luciferase activity among prostatic cancer cells. Then, the results showed a net decrease of miR-373 within prostatic cancer cells and tissues. Upregulated miR-373 reduced the invasion and migration potential of PCa cells. Moreover, overexpressed miR-373 increased the levels of E-cadherin and FSP1 as epithelial cell markers. Similarly, the overregulation of miR-373 brought about the upregulation of mesenchymal markers (N-cadherin, Snail, and vimentin). The study predicted runt-related transcription factor 2 (RUNX2) to be a target of miR-373. The luciferase activity of PCa cells was decreased after the cotransfection with miR-373 mimics and RUNX2 3' untranslated region (3'UTR) wild type (WT). Moreover, RUNX2 became upregulated in PCa cells and tissues. The upregulation of miR-373 decreased the mRNA and protein level of RUNX2. However, overexpressed RUNX2 abated the roles of miR-373 in the intrusion and migration of PCa cells and in regulating the expression of epithelial cell markers and mesenchymal markers. In short, miR-373 may regulate the EMT of PCa cells via targeting RUNX2. The miR-373/RUNX2 axis provides a therapeutic target for PCa.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34261306

RESUMO

Although magnolol (Mag), an anti-inflammatory natural compound, has been demonstrated to play protective effects on ulcerative colitis (UC), its application as an alternative therapeutic reagent for UC treatment is still greatly impeded due to its poor stability in the gastrointestinal tract and insufficient accumulation in the inflamed colon lesion. Nano-/microsized drug delivery systems can potentially overcome some challenges regarding the oral administration of phytochemicals, which still confront premature early drug release, degradation of NPs, or the sustained drug release of MPs. In this study, we primarily loaded Mag into the core-shell zein-based nanoparticles with chondroitin sulfate coating (Mag@CS-Zein NPs) with an average size of 142.27 ± 5.11 nm, showing significant macrophage-targeting and enhanced colon epithelial cellular uptake capacity. Then, we embedded Mag@CS-Zein NPs into hydrogel microspheres via an electrospraying technology. The Mag@CS-Zein NPsinMPs presented a uniform-sized sphere with an average size of 164.36 ± 6.29 µm and sustained drug-release profiles. Compared to CS-Zein NPs, the developed CS-Zein NPsinMPs exhibited prolonged colon retention on the inflammatory surface, as seen from ex vivo and in vivo imaging fluorescence adhesion experiments. Based on the advantage of the combination of hybrid nanoparticles-in-microparticles, oral administration of Mag@CS-Zein NPsinMPs significantly alleviated colitis symptoms in DSS-treated mice by regulating the expression levels of proinflammatory cytokines (TNF-α, IL-6, and IL-1ß) and anti-inflammatory cytokines (IL-10) and factor accelerated colonic mucosal barrier repair via upregulating the expression of ZO-1 and occludin. This study provides great insights into the oral drug delivery of natural compounds for UC therapy.

6.
Molecules ; 26(11)2021 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-34200341

RESUMO

Sinomenine is a morphinan alkaloid with a variety of biological activities. Its derivatives have shown significant cytotoxic activity against different cancer cell lines in many studies. In this study, two series of sinomenine derivatives were designed and synthesized by modifying the active positions C1 and C4 on the A ring of sinomenine. Twenty-three compounds were synthesized and characterized by spectroscopy (IR, 1H-NMR, 13C-NMR, and HRMS). They were further evaluated for their cytotoxic activity against five cancer cell lines, MCF-7, Hela, HepG2, SW480 and A549, and a normal cell line, Hek293, using MTT and CCK8 methods. The chlorine-containing compounds exhibited significant cytotoxic activity compared to the nucleus structure of sinomenine. Furthermore, we searched for cancer-related core targets and verified their interaction with derivatives through molecular docking. The chlorine-containing compounds 5g, 5i, 5j, 6a, 6d, 6e, and 6g exhibited the best against four core targets AKT1, EGFR, HARS and KARS. The molecular docking results were consistent with the cytotoxic results. Overall, results indicate that chlorine-containing derivatives might be a promising lead for the development of new anticancer agents.


Assuntos
Morfinanos/química , Morfinanos/farmacologia , Células A549 , Antineoplásicos/química , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Desenho de Fármacos , Ensaios de Seleção de Medicamentos Antitumorais/métodos , Células HEK293 , Células HeLa , Células Hep G2 , Humanos , Células MCF-7 , Simulação de Acoplamento Molecular/métodos
7.
Asian J Psychiatr ; 62: 102741, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34216978
8.
Cancer Lett ; 520: 109-120, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34237408

RESUMO

The bone marrow microenvironment of acute myeloid leukemia (AML) characterized by immunosuppressive features fosters leukemia immune escape. Elucidating the immunosuppressive mechanism and developing effective immunotherapeutic strategies are necessary. Here, we found that the Th1% and IFN-γ level were downregulated in bone marrow of AML and NLRP3-activated BMDCs promoted CD4+ T cell differentiation into Th1 cells via IL-1ß secretion. However, IFN-γ-producing Th1 cells were not induced by NLRP3-activated BMDCs in the presence of the NLRP3 inflammasome inhibitor MCC950 or anti-IL-1ß antibody in vitro unless exogenous IL-1ß was replenished. This inhibitory effect on Th1 differentiation was also observed in Nlrp3-/- mice or anti-IL-1ß antibody-treated mice. Notably, elevated Th1 cell levels promoted apoptosis and inhibited proliferation in leukemia cells via IFN-γ secretion in vitro and in vivo. Thus, NLRP3-activated BMDCs promote the proliferation of IFN-γ-producing Th1 cells with antileukemic effects and may provide insight into the basis for leukemia immunotherapy in patients with AML.

9.
Neuropharmacology ; 196: 108707, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34246683

RESUMO

Intracochlear electrical stimulation (ES) generated by cochlear implants (CIs) is used to activate auditory nerves to restore hearing perception in deaf subjects and those with residual hearing who use electroacoustic stimulation (EAS) technology. Approximately 1/3 of EAS recipients experience loss of residual hearing a few months after ES activation, but the underlying mechanism is unknown. Clinical evidence indicates that the loss is related to the previous history of noise-induced hearing loss (NIHL). In this report, we investigated the impact of intracochlear ES on oxidative stress levels and synaptic counts in inner hair cells (IHCs) of the apical, middle and basal regions of guinea pigs with normal hearing (NH) and NIHL. Our results demonstrated that intracochlear ES with an intensity of 6 dB above the thresholds of electrically evoked compound action potentials (ECAPs) could induce the elevation of oxidative stress levels, resulting in a loss of IHC synapses near the electrodes in the basal and middle regions of the NH cochleae. Furthermore, the apical region of cochleae with NIHL were more susceptible to synaptic loss induced by relatively low-intensity ES than that of NH cochleae, resulting from the additional elevation of oxidative stress levels and the reduced antioxidant capability throughout the whole cochlea.

10.
Adv Drug Deliv Rev ; : 113870, 2021 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-34280511

RESUMO

As naturally occurring bioactive products, several lines of evidence have shown the potential of polyphenols in the medical intervention of various diseases, including tumors, inflammatory diseases, and cardiovascular diseases. Notably, owing to the particular molecular structure, polyphenols can combine with proteins, metal ions, polymers, and nucleic acids providing better strategies for polyphenol-delivery strategies. This contributes to the inherent advantages of polyphenols as important functional components for other drug delivery strategies, e.g., protecting nanodrugs from oxidation as a protective layer, improving the physicochemical properties of carbohydrate polymer carriers, or being used to synthesize innovative functional delivery vehicles. Polyphenols have emerged as a multifaceted player in novel drug delivery systems, both as therapeutic agents delivered to intervene in disease progression and as essential components of drug carriers. Although an increasing number of studies have focused on polyphenol-based nanodrug delivery including epigallocatechin-3-gallate, curcumin, resveratrol, tannic acid, and polyphenol-related innovative preparations, these molecules are not without inherent shortcomings. The active biochemical characteristics of polyphenols constitute a prerequisite to their high-frequency use in drug delivery systems and likewise to provoke new challenges for the design and development of novel polyphenol drug delivery systems of improved efficacies. In this review, we focus on both the targeted delivery of polyphenols and the application of polyphenols as components of drug delivery carriers, and comprehensively elaborate on the application of polyphenols in new types of drug delivery systems. According to the different roles played by polyphenols in innovative drug delivery strategies, potential limitations and risks are discussed in detail including the influences on the physical and chemical properties of nanodrug delivery systems, and their influence on normal physiological functions inside the organism.

11.
Radiat Oncol ; 16(1): 132, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34281566

RESUMO

BACKGROUND: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is a currently widely used strategy for locally advanced esophageal cancer (EC). However, the conventional imaging methods have certain deficiencies in the evaluation and prediction of the efficacy of nCRT. This study aimed to explore the value of functional imaging in predicting the response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced esophageal squamous cell carcinoma (ESCC). METHODS: Fifty-four patients diagnosed with locally advanced ESCC from August 2017 to September 2019 and treated with nCRT were retrospectively analyzed. DW-MRI scanning was performed before nCRT, at 10-15 fractions of radiotherapy, and 4-6 weeks after the completion of nCRT. 18F-FDG PET/CT scans were performed before nCRT and 4-6 weeks after the completion of nCRT. These 18F-FDG PET/CT and DW-MRI parameters and relative changes were compared between patients with pathological complete response (pCR) and non-pCR. RESULTS: A total of 8 of 54 patients (14.8%) were evaluated as disease progression in the preoperative assessment. The remaining forty-six patients underwent operations, and the pathological assessments of the surgical resection specimens demonstrated pathological complete response (pCR) in 10 patients (21.7%) and complete response of primary tumor (pCR-T) in 16 patients (34.8%). The change of metabolic tumor volume (∆MTV) and change of total lesion glycolysis (∆TLG) were significantly different between patients with pCR and non-pCR. The SUVmax-Tpost, MTV-Tpost, and TLG-Tpost of esophageal tumors in 18F-FDG PET/CT scans after neoadjuvant chemoradiotherapy and the ∆ SUVmax-T and ∆MTV-T were significantly different between pCR-T versus non-pCR-T patients. The esophageal tumor apparent diffusion coefficient (ADC) increased after nCRT; the ADCduring, ADCpost and ∆ADCduring were significantly different between pCR-T and non-pCR-T groups. ROC analyses showed that the model that combined ADCduring with TLG-Tpost had the highest AUC (0.914) for pCR-T prediction, with 90.0% and 86.4% sensitivity and specificity, respectively. CONCLUSION: 18F-FDG PET/CT is useful for re-staging after nCRT and for surgical decision. Integrating parameters of 18F-FDG PET/CT and DW-MRI can identify pathological response of primary tumor to nCRT more accurately in ESCC.

12.
Diagn Microbiol Infect Dis ; 101(2): 115393, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-34237646

RESUMO

We developed and validated a new diagnostic scoring system by simultaneously comparing 28 factors (including clinical, laboratory, and imaging) of HIV uninfected adult tuberculous meningitis (TBM) with viral meningitis (VM), bacterial meningitis (BM), and cryptococcal meningitis (CM). Predictors of TBM diagnosis obtained by logistic regression. A total of 382 patients with intracranial infection participated, and eight factors were independently associated with TBM diagnosis: symptom duration, evidence of extracranial tuberculosis, cerebrospinal fluid (CSF) leukocyte, CSF neutrophil, CSF protein, low serum sodium, meningeal enhancement, and tuberculomas. Factors are assigned according to weight, a score of ≥ 5 was suggestive of TBM with a sensitivity of 85.8% and a specificity of 87.7%, and the area under the receiver operating characteristic curve was 0.923. When applied to a prospective validation cohort, this scoring model showed robust performance. Our study suggests that the application of this score can help diagnose TBM more efficiently.

13.
Acta Biomater ; 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34284151

RESUMO

In the past decade, the study of extracellular vesicles (EVs), especially exosomes (50-150 nm) have attracted growing interest in numerous areas of cancer and tissue regeneration due to their unique biological features. A low isolation yield and insufficient targeting abilities limit their therapeutic applicability. Recently, superparamagnetic iron oxide nanoparticles (SPIONs) with magnetic navigation have been exploited to enhance the targeting ability of EVs. To construct targeted EV delivery systems engineered by SPIONs, several groups have pioneered the use of different techniques, such as electroporation, natural incubation, and cell extrusion, to directly internalize SPIONs into EVs. Furthermore, some endogenous ligands, such as transferrins, antibodies, aptamers, and streptavidin, were shown to enable modification of SPIONs, which increases binding with EVs. In this review, we summarized recent advances in targeted EV delivery systems engineered by SPIONs and focused on the key methodological approaches and the current applications of magnetic EVs. This report aims to address the existing challenges and provide comprehensive insights into targeted EV delivery systems. STATEMENT OF SIGNIFICANCE: : Targeted extracellular vesicle (EV) delivery systems engineered by superparamagnetic iron oxide nanoparticles (SPIONs) have attracted wide attention and research interest in recent years. Such strategies employ external magnet fields to manipulate SPION-functionalized EVs remotely, aiming to enhance their accumulation and penetration in vivo. Although iron oxide nanoparticle laden EVs are interesting, they are controversial at present, hampering the progress in their clinical application. A thorough integration of these studies is needed for an advanced insight and rational design of targeted EV delivery systems. In this review, we summarize the latest advances in the design strategies of targeted EV delivery systems engineered by SPIONs with a focus on their key methodological approaches, current applications, limitation and future perspectives, which may facilitate the development of natural theranostic nanoplatforms.

14.
Front Immunol ; 12: 661939, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211462

RESUMO

NLRP3 inflammasome has been reported to be associated with the pathogenesis of multiple solid tumors. However, the role of NLRP3 inflammasome in acute myeloid leukemia (AML) remains unclear. We showed that NLRP3 inflammasome is over-expressed and highly activated in AML bone marrow leukemia cells, which is correlated with poor prognosis. The activation of NLRP3 inflammasome in AML cells promotes leukemia cells proliferation, inhibits apoptosis and increases resistance to chemotherapy, while inactivation of NLRP3 by caspase-1 or NF-κB inhibitor shows leukemia-suppressing effects. Bayesian networks analysis and cell co-culture tests further suggest that NLRP3 inflammasome acts through IL-1ß but not IL-18 in AML. Knocking down endogenous IL-1ß or anti-IL-1ß antibody inhibits leukemia cells whereas IL-1ß cytokine enhances leukemia proliferation. In AML murine model, up-regulation of NLRP3 increases the leukemia burden in bone marrow, spleen and liver, and shortens the survival time; furthermore, knocking out NLRP3 inhibits leukemia progression. Collectively, all these evidences demonstrate that NLRP3 inflammasome promotes AML progression in an IL-1ß dependent manner, and targeting NLRP3 inflammasome may provide a novel therapeutic option for AML.

15.
Dis Markers ; 2021: 6680883, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34211612

RESUMO

Background: Glioma is the most common primary intracranial tumor and is associated with poor prognosis. Identifying effective biomarkers for glioma is particularly important. MXRA5, a secreted glycoprotein, is involved in cell adhesion and extracellular matrix remodeling and has been reported to be expressed in many cancers. However, the role and mechanism of action of MXRA5 in gliomas remain unclear. This study was aimed at investigating the role of MXRA5 at the transcriptome level and its clinical prognostic value. Methods: In this study, RNA microarray data of 301 glioma patients from the Chinese Glioma Genome Atlas (CGGA) were collected as a training cohort and RNA-seq data of 702 glioma samples from The Cancer Genome Atlas (TCGA) were used for validation. We analyzed the clinical and molecular characteristics as well as the prognostic value of MXRA5 in glioma. In addition, the expression level of MXRA was evaluated in 28 glioma tissue samples. Results: We found that MXRA5 expression was significantly upregulated in high-grade gliomas and IDH wild-type gliomas compared to controls. Receiver operating characteristic (ROC) analysis showed that MXRA5 is a potential marker of the mesenchymal subtype of glioblastoma multiforme (GBM). We found that MXRA5 expression is highly correlated with immune checkpoint molecule expression levels and tumor-associated macrophage infiltration. High MXRA5 expression could be used as an independent indicator of poor prognosis in glioma patients. Conclusion: Our study suggests that MXRA5 expression is associated with the clinicopathologic features and poor prognosis of gliomas. MXRA5 may play an important role in the immunosuppressive microenvironment of glioma. As a secreted glycoprotein, MXRA5 is a potential circulating biomarker for glioma, deserving further investigation.

16.
Artigo em Inglês | MEDLINE | ID: mdl-34215500

RESUMO

BACKGROUND: Acute cellular rejection (ACR) remains the most significant risk factor for chronic lung allograft dysfunction (CLAD). While clinically significant or higher-grade (≥A2) ACR is generally treated with augmented immunosuppression (IS), the management of clinically stable grade A1 ACR remains controversial. At our center, patients with clinically stable grade A1 ACR are routinely not treated with augmented IS. While the overall outcomes in this group of patients at our center are equivalent to patients with stable A0 pathology, CLAD and death rates remain overall high. We hypothesized that a distinct cytokine signature at the time of early minimal rejection state would be associated with worse outcomes. Specifically, we aimed to determine whether bronchoalveolar lavage (BAL) biomarkers at the time of first clinically stable grade A1 ACR (CSA1R) are predictive of subsequent CLAD or death. METHODS: Among all adult, bilateral, first lung transplants, performed 2010-2016, transbronchial biopsies obtained within the first-year post-transplant were categorized as clinically stable or unstable based on the presence or absence of ≥10% concurrent drop in forced expiratory volume in 1 second (FEV1). We assessed BAL samples obtained at the time of CSA1R episodes, which were not preceded by another ACR (i.e., first episodes). Twenty-one proteins previously associated with ACR or CLAD were measured in the BAL using a multiplex bead assay. Association between protein levels and subsequent CLAD or death was assessed using Cox Proportional Hazards models, adjusted for relevant peri-transplant clinical covariates. RESULTS: We identified 75 patients with first CSA1R occurring at a median time of 98 days (range 48.5-197) post-transplant. Median time from transplant to CLAD or death was 1247 (756.5-1921.5) and 1641 days (1024.5-2326.5), respectively. In multivariable models, levels of MCP1/CCL2, S100A8, IL10, TNF-receptor 1, and pentraxin 3 (PTX3) were associated with both CLAD development and death (p < 0.05 for all). PTX3 remained significantly associated with both CLAD and death after adjusting for multiple comparisons. CONCLUSION: Our data indicate that a focused BAL protein signature, with PTX3 having the strongest association, may be useful in determining a subset of CSA1R patients at increased risk and may benefit from a more aggressive management strategy.

17.
Neurosci Bull ; 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215968

RESUMO

Mechanosensitive ion channels (MSCs) are key molecules in the mechano-electrical transduction of arterial baroreceptors. Among them, acid-sensing ion channel 2 (ASIC2) and transient receptor potential vanilloid subfamily member 1 (TRPV1) have been studied extensively and documented to play important roles. In this study, experiments using aortic arch-aortic nerve preparations isolated from rats revealed that both ASIC2 and TRPV1 are functionally necessary, as blocking either abrogated nearly all pressure-dependent neural discharge. However, whether ASIC2 and TRPV1 work in coordination remained unclear. So we carried out cell-attached patch-clamp recordings in HEK293T cells co-expressing ASIC2 and TRPV1 and found that inhibition of ASIC2 completely blocked stretch-activated currents while inhibition of TRPV1 only partially blocked these currents. Immunofluorescence staining of aortic arch-aortic adventitia from rats showed that ASIC2 and TRPV1 are co-localized in the aortic nerve endings, and co-immunoprecipitation assays confirmed that the two proteins form a compact complex in HEK293T cells and in baroreceptors. Moreover, protein modeling analysis, exogenous co-immunoprecipitation assays, and biotin pull-down assays indicated that ASIC2 and TRPV1 interact directly. In summary, our research suggests that ASIC2 and TRPV1 form a compact complex and function synergistically in the mechano-electrical transduction of arterial baroreceptors. The model of synergism between MSCs may have important biological significance beyond ASIC2 and TRPV1.

18.
Adipocyte ; 10(1): 293-309, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34060407

RESUMO

Extracellular vesicles (EVs) are specific subcellular vesicles released by cells under various environmental conditions. Tumescent liposuction is a commonly used procedure in plastic surgery practice. In the present study, we aimed to extract EVs derived from lipoaspirate fluid (LF-EVs) and characterize them using transmission electron microscopy, nanoparticle tracking analysis, and western blotting. The global profiles of proteins and microRNAs from LF-EVs were identified, strongly suggesting a potential regulatory function of LF-EVs. In addition, we investigated the effects and mechanisms of LF-EVs on fat graft survival. Cell functional tests showed that LF-EVs promoted the proliferation, migration, and tube structure formation of human umbilical vein endothelial cells. LF-EVs also promoted the adipogenic differentiation of adipose tissue-derived stem cells. The results of animal experiments showed that the average weights of fat grafts in the LF-EVs-treated group were significantly higher than those in the control group. Histologically, there was less fibrosis, fewer cysts, and increased fat tissue survival in the LF-EVs group. Further investigations of angiogenic and adipogenic factors revealed that LF-EVs also promoted angiogenesis and exerted a pro-adipogenic effect in vivo. Our findings will help to elucidate the functions of LF-EVs and provide a reference dataset for future translational studies.

19.
Ear Nose Throat J ; : 1455613211022079, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34151581

RESUMO

Mucormycosis of temporal bone is extremely rare. They are usually associated with host immunodeficiency, are difficult to diagnose, and many cases are fatal. We performed a literature review and found only 10 reported cases of temporal bone mucormycosis. We present a case of temporal bone mucormycosis involving the temporomandibular joint and infratemporal fossa in a 53-year-old woman with diabetes mellitus who presented with unbearable otalgia. Computed tomography and magnetic resonance imaging demonstrate inhomogeneous density mass in the parapharyngeal and retropharyngeal space accompanied with lytic bone destruction on the temporomandibular joint. After undergoing a biopsy of the left infratemporal fossa, the patient's pathology exhibited fungal hyphae consistent with mucormycosis. To our knowledge, this is the first report of temporal bone mucormycosis with extensive involvement of temporomandibular joint and its adjacent structures, which exhibited no otologic or rhinologic signs. A definitive diagnosis is made by biopsy.

20.
Nat Cell Biol ; 23(6): 642-651, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34059812

RESUMO

In the last decade, DNA-based tension sensors have made significant contributions to the study of the importance of mechanical forces in many biological systems. Albeit successful, one shortcoming of these techniques is their inability to reversibly measure receptor forces in a higher regime (that is, >20 pN), which limits our understanding of the molecular details of mechanochemical transduction in living cells. Here, we developed a reversible shearing DNA-based tension probe (RSDTP) for probing molecular piconewton-scale forces between 4 and 60 pN transmitted by cells. Using these probes, we can easily distinguish the differences in force-bearing integrins without perturbing adhesion biology and reveal that a strong force-bearing integrin cluster can serve as a 'mechanical pivot' to maintain focal adhesion architecture and facilitate its maturation. The benefits of the RSDTP include a high dynamic range, reversibility and single-molecule sensitivity, all of which will facilitate a better understanding of the molecular mechanisms of mechanobiology.

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