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1.
J Ethnopharmacol ; 291: 115145, 2022 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-35219821

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Shenling Baizhu San (SBS) is commonly employed to improve gastrointestinal dysfunction in patients with ulcerative colitis (UC) in China. SBS combined with mesalamine has been demonstrated to result in improve its curative effects without increasing any adverse reactions, but the underlying mechanism remains unclarified. AIM OF THE STUDY: Our study aimed to illuminate the potential therapeutic effects and mechanisms of SBS, which is a medicine complementary to mesalamine, in the treatment of UC. MATERIALS AND METHODS: A prospective cohort study was conducted to evaluate the efficacy of SBS as a complementary medicine to mesalamine for patients with UC (n = 48). The patients in the control group (n = 24) were given mesalamine alone, whereas those in the experimental group were administered mesalamine combined with SBS. The therapeutic outcome was assessed at 8 weeks. The structures of the gut microbiota (GMB) were characterized by 16S rRNA sequencing, and the microbial tryptophan metabolites were analyzed by UPLC-MS/MS to investigate the mechanism through which SBS achieves its effects. RESULTS: Our results showed that the combination of SBS and mesalamine could significantly improve the clinical signs of UC by achieving mucosal healing and relieving colon damage. Interestingly, the combination of SBS and mesalamine could alter the GMB structures and increase the microbial levels of tryptophan metabolites, including indole-3-propionic acid and indole-3-acetic acid. CONCLUSION: SBS combined with mesalamine is effective in improving the clinical and endoscopic outcomes of patients with UC. SBS, as a complementary therapy to conventional treatment, alleviates UC via the GMB-tryptophan metabolite axis.


Assuntos
Colite Ulcerativa , Terapias Complementares , Microbioma Gastrointestinal , Cromatografia Líquida , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Medicamentos de Ervas Chinesas , Humanos , Mesalamina/farmacologia , Mesalamina/uso terapêutico , Estudos Prospectivos , RNA Ribossômico 16S , Espectrometria de Massas em Tandem , Triptofano
2.
Front Hum Neurosci ; 16: 935213, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36092649

RESUMO

Background: Primary angle-closure glaucoma (PACG) is a serious and irreversible blinding eye disease. Growing studies demonstrated that PACG patients were accompanied by vision and vision-related brain region changes. However, whether the whole-brain functional network hub changes occur in PACG patients remains unknown. Purpose: The purpose of the study was to investigate the brain function network hub changes in PACG patients using the voxel-wise degree centrality (DC) method. Materials and methods: Thirty-one PACG patients (21 male and 10 female) and 31 healthy controls (HCs) (21 male and 10 female) closely matched in age, sex, and education were enrolled in the study. The DC method was applied to investigate the brain function network hub changes in PACG patients. Moreover, the support vector machine (SVM) method was applied to distinguish PACG patients from HC patients. Results: Compared with HC, PACG patients had significantly higher DC values in the right fusiform, left middle temporal gyrus, and left cerebelum_4_5. Meanwhile, PACG patients had significantly lower DC values in the right calcarine, right postcentral gyrus, left precuneus gyrus, and left postcentral gyrus. Furthermore, the SVM classification reaches a total accuracy of 72.58%, and the ROC curve of the SVM classifier has an AUC value of 0.85 (r = 0.25). Conclusion: Our results showed that PACG patients showed widespread brain functional network hub dysfunction relative to the visual network, auditory network, default mode network, and cerebellum network, which might shed new light on the neural mechanism of optic atrophy in PACG patients.

3.
J Hazard Mater ; 439: 129567, 2022 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-36104894

RESUMO

The separation of oily wastewater, specifically emulsions, is a crucial global issue. Possible strategies for the efficient separation of emulsified oil/water mixtures through sustainable and environmentally friendly materials have recently drawn considerable attention. In our study, we prepared superwetting water caltrop shell biochar (WCSB) via a top-lit-updraft carbonization procedure. The as-prepared WCSB was characterized by superhydrophilicity, underwater superoleophobicity, underoil superhydrophilicity, and underoil water adsorption ability. Because of its superwetting properties, WCSB was used for the separation of both surfactant-stabilized oil-in-water emulsions (SOIWEs) and surfactant-stabilized water-in-oil emulsions (SWIOEs) with very high fluxes (up to 74,700 and 241,000 L m-2 h-1 bar-1 for SOIWE and SWIOE, respectively). The separation performances were excellent, with oil contents in all SOIWE filtrates lower than 10 ppm and oil purities in all SWIOE filtrates higher than 99.99 wt%. Moreover, WCSB was applied to separate dye-spiked emulsions. Due to their high emulsion separation ability, sustainability, good biocompatibility, and ease of mass production, the as-prepared WCSBs have notable potential for utilitarian applications.


Assuntos
Óleos , Águas Residuárias , Carvão Vegetal , Emulsões , Tensoativos
4.
Anal Chem ; 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36121799

RESUMO

As a critical functional protein in DNA replication and genome stability, flap endonuclease 1 (FEN1) has been considered a promising biomarker and druggable target for multiple cancers. We report here a transcription-powered clustered regularly interspaced short palindromic repeat (CRISPR)/Cas12a signal expansion platform for rapid and sensitive detection of FEN1. In this method, the probe cleavage by FEN1 generated a free 5' flap single-stranded DNA which could hybridize with the single-stranded T7 promoter-bearing template and trigger the extension. Then, the CRISPR guide RNA (crRNA) transcribed from the extended template activated the collateral DNase activity of Cas12a, releasing the fluorophore from the quenched DNA signal probe to report the FEN1 detection result. The high specificity for FEN1 was validated by comparing with other repair-relevant proteins. The limit of detection (LOD) could be as low as 0.03 mU, which is sensitive enough to detect the FEN1 activity in biological samples. In addition, the inhibition assay of FEN1 was also successfully achieved with this platform, proving its potential in inhibitor screening. In summary, this study provides a novel biosensor for FEN1 activity analysis and provides new insights into the development of CRISPR-based biosensors for non-nucleic acid targets.

5.
Front Cell Infect Microbiol ; 12: 945284, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36105146

RESUMO

Objectives: The present study aimed to investigate the characteristics of salivary microbiota of children with obstructive sleep apnea (OSA) and to assess longitudinal alterations in salivary microbiota before and after adenotonsillectomy. Methods: A set of cross-sectional samples consisted of 36 OSA children (17 boys and 19 girls, 7.47 ± 2.24 years old) and 22 controls (9 boys and 13 girls, 7.55 ± 2.48 years old) were included in the study, among which eight OSA children (five boys and three girls, 8.8 ± 2.0 years old) who underwent treatment of adenotonsillectomy were followed up after 1 year. Saliva samples were collected, and microbial profiles were analyzed by bioinformatics analysis based on 16S rRNA sequencing. Results: In cross-sectional samples, the OSA group had higher α-diversity as estimated by Chao1, Shannon, Simpson, Pielou_e, and observed species as compared with the control group (p < 0.05). ß-Diversity based on the Bray-Curtis dissimilarities (p = 0.004) and Jaccard distances (p = 0.001) revealed a significant separation between the OSA group and control group. Nested cross-validated random forest classifier identified the 10 most important genera (Lactobacillus, Escherichia, Bifidobacterium, Capnocytophaga, Bacteroidetes_[G-7], Parvimonas, Bacteroides, Klebsiella, Lautropia, and Prevotella) that could differentiate OSA children from controls with an area under the curve (AUC) of 0.94. Linear discriminant analysis effect size (LEfSe) analysis revealed a significantly higher abundance of genera such as Prevotella (p = 0.027), Actinomyces (p = 0.015), Bifidobacterium (p < 0.001), Escherichia (p < 0.001), and Lactobacillus (p < 0.001) in the OSA group, among which Prevotella was further corroborated in longitudinal samples. Prevotella sp_HMT_396 was found to be significantly enriched in the OSA group (p = 0.02) with significantly higher levels as OSA severity increased (p = 0.014), and it had a lower abundance in the post-treatment group (p = 0.003) with a decline in each OSA child 1 year after adenotonsillectomy. Conclusions: A significantly higher microbial diversity and a significant difference in microbial composition and abundance were identified in salivary microbiota of OSA children compared with controls. Meanwhile, some characteristic genera (Prevotella, Actinomyces, Lactobacillus, Escherichia, and Bifidobacterium) were found in OSA children, among which the relationship between Prevotella spp. and OSA is worth further studies.


Assuntos
Microbiota , Apneia Obstrutiva do Sono , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Microbiota/genética , Polissonografia , Prevotella/genética , Estudos Prospectivos , RNA Ribossômico 16S/genética
6.
J Control Release ; 2022 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-36122895

RESUMO

Photodynamic therapy (PDT) can produce a large amount of reactive oxygen species (ROS) in the radiation field to kill tumor cells. However, the sustainable anti-tumor efficacy of PDT is limited due to the hypoxic microenvironment of tumor. In this study, classic PDT agent indocyanine green (ICG) and hypoxia-activated chemotherapeutic drug tirapazamine (TPZ) were loaded on mesoporous polydopamine (PDA) to construct PDA@ICG-TPZ nanoparticles (PIT). Then, PIT was camouflaged with cyclic arginine-glycine-aspartate (cRGD) modified tumor cell membranes to obtain the engineered membrane-coated nanoreactor (cRGD-mPIT). The nanoreactor cRGD-mPIT could achieve the dual-targeting ability via tumor cell membrane mediated homologous targeting and cRGD mediated active targeting. With the enhanced tumor-targeting and penetrating delivery system, PIT could efficiently accumulate in hypoxic tumor cells and the loaded drugs were quickly released in response to near-infrared (NIR) laser. The nanoreactor might produce cytotoxic ROS under NIR and further enhance hypoxia within tumor to activate TPZ, which efficiently inhibited hypoxic tumor by synergistic photodynamic-chemotherapy. Mechanically, hypoxia-inhibitory factor-1α (HIF-1α) was down-regulated by the synergistic therapy. Accordingly, the cRGD-mPIT nanoreactor with sustainable and cascade anti-tumor effects and satisfied biosafety might be a promising strategy in hypoxic tumor therapy.

7.
Artigo em Inglês | MEDLINE | ID: mdl-36123509

RESUMO

With the rapid development of unconventional natural gas such as shale gas, many oil-based drilling cuttings and their pyrolysis residues are produced, which are defined as hazardous wastes. In this paper, the pollution status of petroleum hydrocarbons and the leaching toxicity of eight heavy metals (Pb, Cr, Zn, Mn, Cu, Cd, Ni, and Hg) in the pyrolysis residues were studied. The ecological risk and human health risk were evaluated in the scenario where pyrolytic residues were used for paving as building materials. The results showed that the content of petroleum hydrocarbons in the pyrolysis residues was 7643.16 ± 169.67 mg/kg. Zn in the pyrolysis residues was extremely polluted, Pb was moderately polluted, Cr, Cu, As were slightly polluted, and the leaching toxicity was far below the standard value. In the ecological risk assessment, the comprehensive potential ecological risk of multiple heavy metals in the pyrolysis residues was low. On the other hand, the pyrolysis residues had no non-carcinogenic risk to adults under the condition of paving, but there was an obvious non-carcinogenic risk to children, and the carcinogenic risk of adults and children was within an acceptable range. In addition, aiming at reducing the health risk of the population, suggestions were put forward to reduce the exposure risk of the population and the content of heavy metals in the pyrolysis residue, which provided a scientific reference for the standardized management of the pyrolysis residue of oil-based drilling cuttings and the research on the corresponding treatment process.

8.
Adv Healthc Mater ; : e2200955, 2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36123781

RESUMO

Osteosarcoma is a rare malignant bone-originating tumor that usually occurs in young people. Programmed cell death 1 ligand 1 (PD-L1), an immune checkpoint protein, is highly expressed in osteosarcoma tissues. Several recent studies have indicated that the tumor-related role of PD-L1 in tumors, especially non-plasma membrane (NPM)-localized PD-L1, is not limited to immune regulation in osteosarcoma. Here, we combined mass spectrometry analysis with RNA-seq examination to identify the intracellular binding partners of PD-L1 and elucidate the underlying mechanism of its action. We found that NPM-localized PD-L1 interacted with Insulin-like growth factor binding protein-3 (IGFBP3) to promote osteosarcoma tumor growth by activating mTOR signaling. This interaction was enforced after phosphoglyceratekinase1 (PGK1)-mediated PD-L1 phosphorylation. Based on these findings, we designed a phosphorylation-mimicking peptide from PD-L1 and encapsulated it with a Cyclic RGD (cRGD)-modified red blood cell membrane (RBCM) vesicle (Peptide@cRGD-M). The Peptide@cRGD-M precisely delivered the PD-L1-derived phosphorylation-mimicking peptide into osteosarcoma lesions and significantly promoted its therapeutic effect on the tumor. Therefore, our investigation not only highlighted the function of NPM-localized PD-L1 but also used an engineering approach to synthesize a small molecular peptide capable of inhibiting osteosarcoma growth. This article is protected by copyright. All rights reserved.

9.
Nanoscale ; 14(36): 13248-13260, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36052817

RESUMO

In conventional thermocatalytic reactions under a reducing atmosphere, stabilization of the active Cu+ component and inhibition of over-reduction into metallic Cu0 are extremely challenging. In this study, Au@Cu2O core-shell nano-catalysts with different Cu2O shell thicknesses were synthesized, and the effect of the Au nano-core on Cu+ stability under a reducing atmosphere and the catalytic performance of Cu+ in the ethynylation of formaldehyde were investigated. The Au nano-core facilitates Cu2O dispersion and leads to an increase of 0.2-0.5 eV in electron binding energies of Cu2O and Cu2C2 in the range of 27-55 nm, attributed to the long-range electromagnetic effect of Au NPs. Specifically, active Cu+ centers exhibit high stability under a reducing atmosphere due to the long-range electromagnetic effect of the Au nano-core. In the ethynylation of formaldehyde as a probe reaction, Cu+/(Cu0 + Cu+) on Au@Cu2O catalysts remained at 88-91%. The catalytic performance in the ethynylation of formaldehyde revealed that the introduction of an Au nano-core into Cu-based catalysts increased the TOF from 0.37 to 0.7 h-1, and decreased the activation energy from 42.6 to 38.1 kJ mol-1. Additionally, the Cu+/(Cu0 + Cu+) ratios and the catalytic performance in the ethynylation of formaldehyde (BD yield = 65%, BD selectivity = 95%) on Au@Cu2O catalysts remained constant after nine cycles, while pure Cu2O readily deactivated due to the dramatically reduced Cu+/(Cu0 + Cu+) ratios and carbyne deposition. In summary, Cu+ in Cu-based catalysts showed high catalytic activity and stability during the ethynylation of formaldehyde due to the long-range electromagnetic effect of the Au nano-core.

10.
Nat Cancer ; 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36050483

RESUMO

Increasing evidence shows that cancer cells can disseminate from early evolved primary lesions much earlier than the classical metastasis models predicted. Here, we reveal at a single-cell resolution that mesenchymal-like (M-like) and pluripotency-like programs coordinate dissemination and a long-lived dormancy program of early disseminated cancer cells (DCCs). The transcription factor ZFP281 induces a permissive state for heterogeneous M-like transcriptional programs, which associate with a dormancy signature and phenotype in vivo. Downregulation of ZFP281 leads to a loss of an invasive, M-like dormancy phenotype and a switch to lung metastatic outgrowth. We also show that FGF2 and TWIST1 induce ZFP281 expression to induce the M-like state, which is linked to CDH1 downregulation and upregulation of CDH11. We found that ZFP281 not only controls the early dissemination of cancer cells but also locks early DCCs in a dormant state by preventing the acquisition of an epithelial-like proliferative program and consequent metastases outgrowth.

11.
Magn Reson Med ; 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-36111354

RESUMO

PURPOSE: To investigate the effects of gadolinium (Gd) retention of macrocyclic (gadobutrol) or linear (gadopentetate) Gd-based contrast agents (GBCAs) on neuron loss, neurological deficits, and sensory behavior in mice with or without stroke. METHODS: Ninety C57BL/6 mice underwent sham (n = 36) or transient middle cerebral artery occlusion (tMCAO) (n = 54) surgery and then received intraperitoneal injections of 5.0 mmol/kg gadobutrol, 5.0 mmol/kg gadopentetate or saline (10 ml/kg/administration) per day for 3 consecutive days. The Gd concentration in the ischemic cerebrum was quantified by inductively coupled plasma mass spectrometry on Day 1 and Day 28 after the last injection (post-injection, p. i.). Neuron loss, glia activation and neurological deficits were assessed on Day 1 and 28 p. i. Sensory behavior was also assessed on Day 28 p. i. RESULTS: Gd concentrations were higher in the brains of tMCAO mice than in those of sham mice on Days 1 p. i. of both GBCAs (gadobutrol, p < 0.05; gadopentetate, p < 0.001) and 28 p. i of gadopentetate. (p < 0.001). Sham or tMCAO mice injected with GBCAs showed no significant difference in neuron loss, glia activation, neurological deficits, brain atrophy, or hippocampus-dependent memory (all p > 0.05). Both gadobutrol and gadopentetate induced mechanical and heat hyperalgesia in sham mice (all p < 0.05). However, mechanical hyperalgesia but rather heat hyperalgesia was found in tMCAO mice with the highest force tested (1.0 g) and statistically significant in both paws (right and left) with gadopentetate only (p < 0.05). CONCLUSIONS: Neither gadobutrol nor gadopentetate worsened neuron loss, glia activation, brain atrophy, neurological deficits, or hippocampus-dependent memory after tMCAO. However, GBCA administration induced mechanical hyperalgesia in sham and tMCAO mice although in the same level, which may be an important consideration for patients with central post-stroke pain and those who are sensitive to pain and about to receive multiple GBCA administrations.

12.
Adv Sci (Weinh) ; : e2204247, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104244

RESUMO

Advanced exfoliation techniques are crucial for exploring the intrinsic properties and applications of 2D materials. Though the recently discovered Au-enhanced exfoliation technique provides an effective strategy for the preparation of large-scale 2D crystals, the high cost of gold hinders this method from being widely adopted in industrial applications. In addition, direct Au contact could significantly quench photoluminescence (PL) emission in 2D semiconductors. It is therefore crucial to find alternative metals that can replace gold to achieve efficient exfoliation of 2D materials. Here, the authors present a one-step Ag-assisted method that can efficiently exfoliate many large-area 2D monolayers, where the yield ratio is comparable to Au-enhanced exfoliation method. Differing from Au film, however, the surface roughness of as-prepared Ag films on SiO2 /Si substrate is much higher, which facilitates the generation of surface plasmons resulting from the nanostructures formed on the rough Ag surface. More interestingly, the strong coupling between 2D semiconductor crystals (e.g., MoS2 , MoSe2 ) and Ag film leads to a unique PL enhancement that has not been observed in other mechanical exfoliation techniques, which can be mainly attributed to enhanced light-matter interaction as a result of extended propagation of surface plasmonic polariton (SPP). This work provides a lower-cost and universal Ag-assisted exfoliation method, while at the same time offering enhanced SPP-matter interactions.

13.
Clin Transl Oncol ; 2022 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-36115931

RESUMO

PURPOSE: Checkpoint immunotherapy is a promising treatment option for advanced cervical cancer. To aid in selecting patients for this treatment, we identified potential predictors of the response to anti-PD-1 combination therapy. METHODS: We simultaneously characterized CD8+, FoxP3+, PD-L1+, CD68+, CD31+, PANCK+, and PANCK-PD-L1+ cells at the invasive margin (IM) of tumor by multispectral imaging of tissue sections from 37 patients with advanced cervical cancer in our previous trial cohort. The densities of each cell and cell-to-cell topography were compared between the responder and non-responder groups and evaluated for their predictive value in clinical response and survival. RESULTS: CD8+ T cells, PD-L1+ cells, and PANCK-PD-L1+ immune cells showed higher densities at the IM in the responders than in the non-responders (P = 0.022, 0.0094, and 0.049, respectively). A higher density of CD8+ T cells at the IM was related to prolonged progression-free survival (PFS; P = 0.031). A higher ratio of CD68+/CD8+ cells was found in the non-responder group (P = 0.003) and related to poor PFS (P = 0.016). A higher density of PANCK-PD-L1+ immune cells within 20, 30, and 45 µm of PANCK+ tumor cells was correlated with better clinical response (P = 0.017, 0.017, and 0.02, respectively). CONCLUSIONS: Multiparametric immune profiling of CD8+ T cells, PD-L1+ cells, CD68+ macrophages and PANCK-PD-L1+ immune cells at the invasive margin may help identify patients with cervical cancer who may benefit from anti-PD-1 combination therapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials. gov identifier: NCT03816553, January 25, 2019.

14.
J Clin Ultrasound ; 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36054377

RESUMO

PURPOSE: We described the accuracy of ultrasound in determining the position of bronchial blockers (BBs) in children underwent thoracoscopic surgery. METHODS: We enrolled 52 children with ASA grade I-III who received thoracoscopic surgery with placement of BBs. Point-of-care ultrasound was performed according to the BLUE protocol. The ultrasound-guided lung sliding sign and curtain sign were used to assess the position of BBs. The accuracy of ultrasound in evaluating the position of BBs, as well as the accuracy and operating time of sliding sign and curtain sign at each examination point were recorded and compared. RESULTS: The accuracy of ultrasound in evaluating the position of BBs was 88% (46/52, 95% CI 0.69-0.97). When using the curtain sign to assess the position of BBs, the accuracy was 90% (94/104, 95% CI 0.78-0.96), which was significantly higher than when using the sliding sign (65% (136/208), 95% CI 0.55-0.74) (p = 0.002). The accuracy of curtain sign at the left mid-axillary line-diaphragm and the right mid-axillary line-diaphragm was respectively 96% (50/52, 95% CI 0.80-0.99) and 84% (44/52, 95% CI 0.65-0.95), which were higher than that of sliding sign at upper blue points and lower blue points. There was no significant difference in the operating time between two ultrasound signs (the curtain sign, 13.4 ± 8.2 s vs. the lung sliding sign, 16.2 ± 10.0 s, p = 0.065). CONCLUSION: Point-of-care ultrasound can effectively assess the position of BBs. The accuracy of using the curtain sign at the mid-axillary line-diaphragm is higher than that of using the lung sliding sign at the anterior chest wall.

15.
Stat Med ; 2022 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-36053782

RESUMO

Development of marker signatures to predict treatment benefits for a new therapeutic is an important scientific component in advancing the drug discovery and is an important first step toward the goal of precision medicine. In this article, we focus on developing an algorithm to search for optimal linear combination of markers that maximizes the area between two receiver operating characteristic curves of the new therapeutic and the control groups without assuming any parametric model. We further generalize the proposed algorithm for predictive signature development to maximize the difference of Harrel's C-index of the new therapeutic and the control groups when the outcome of interest is time-to-event. The performance of this proposed method is evaluated and compared to existing methods via simulations and real clinical trial data.

16.
Int J Mol Sci ; 23(17)2022 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-36077001

RESUMO

Meibomian gland orifices (MGOs) are located along the eyelid margin and secrete meibum into the tear film. The profile of resident innate immune cells (ICs) at this site is not well understood. The distribution and phenotype of resident ICs around MGOs in mice was investigated and herein defined as MGO-associated immune cells (MOICs). The effect of topical 0.1% benzalkonium chloride (BAK) on MOICs was also assessed. Eyelids from healthy CD11ceYFP and Cx3cr1gfp/gfp mice aged three or seven months were compared. ICs were identified as CD11c+, Cx3cr1+, and MHC-II+ using four-colour immunostaining and confocal microscopy. MOIC density was variable but clustered around MGOs. There were more CD11c+ MOICs in three-month-old compared with seven-month-old mice (three-month-old: 893&nbsp;±&nbsp;449 cells/mm2 vs. seven-month-old: 593&nbsp;±&nbsp;493 cells/mm2, p = 0.004). Along the eyelid margin, there was a decreasing gradient of CD11c+ MOIC density in three-month-old mice (nasal: 1003&nbsp;±&nbsp;369 cells/mm2, vs. central: 946&nbsp;±&nbsp;574 cells/mm2, vs. temporal: 731&nbsp;±&nbsp;353 cells/mm2, p = 0.044). Cx3cr1-deficient mice had two-fold fewer MHC-II+ MOICs, suggesting a role for Cx3cr1 receptor signaling in meibomian gland surveillance. CD11c+ MOIC density was lower in BAK-exposed eyes compared to saline-treated controls, suggesting a change in homeostasis. This study provides novel insight into resident ICs located at MGOs, and their contribution to MG homeostasis.


Assuntos
Doenças Palpebrais , Glândulas Tarsais , Animais , Compostos de Benzalcônio/farmacologia , Camundongos , Fenótipo , Lágrimas
17.
Neuroreport ; 33(14): 604-611, 2022 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-36062513

RESUMO

The purpose of the study is to use the voxel-mirrored homotopic connectivity (VMHC) technique to explore the pattern of the interhemispheric functional connectivity in patients with primary angle-closure glaucoma (PACG). The interhemispheric functional connectivity was compared between 31 individuals with PACG and 31 healthy controls closely matched with sex, age, and educational level using the VMHC technique. Significant differences in VMHC between two groups were selected to be classification features for classifying individuals with PACG from healthy controls using the support vector machine algorithm of the machine learning. We used the permutation test analysis to assess the classification performance. In addition, the Pearson analysis was applied to explore the relationship between changed VMHC and clinical varieties in patients with PACG. Compared with healthy controls, individuals with PACG exhibited significantly lower VMHC signal values in the right calcarine, right cuneus, right superior occipital gyrus, and right postcentral gyrus [voxel level: P < 0.001, Gaussian random field correction, cluster level: P < 0.05]. Moreover, the results displayed that the total accuracy, sensitivity, and specificity of the machine learning classification were 0.758, 0.710, and 0.807, respectively (P < 0.001, nonparametric permutation test). The findings demonstrated that there is disturbed interhemispheric resting-state functional connectivity in the vision-related brain areas of individuals with PACG; and the VMHC variability can classify individuals with PACG from healthy controls with high accuracy, which provided novel evidence for understanding the neuropathological mechanism of PACG.


Assuntos
Glaucoma de Ângulo Fechado , Encéfalo , Mapeamento Encefálico , Estudos de Casos e Controles , Glaucoma de Ângulo Fechado/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética/métodos
18.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 38(3): 264-269, 2022 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-36062797

RESUMO

Objective: To investigate the effects of exogenous hydrogen sulfide (H2S) on pulmonary vascular reactivity induced by endotoxic shock (ES) in rabbits. Methods: In this experiment, the model of endotoxic shock (ES) was induced by injection of lipopolysaccharides (LPS) to New Zealand big eared white rabbit through jugular vein (8 mg/0.8 ml/kg), the intervention was performed by H2S donor(sodium hydrosulfide, NaHS) which was injected intraperitoneally (28 µmol/kg) 15 min in advance. New Zealand rabbits were randomly divided into 4 groups(n=8):control group, LPS group, LPS+NaHS group and NaHS group. The changes of mean arterial pressure (MAP) and mean pulmonary arterial pressure (MPAP) were detected. The tension of pulmonary artery ring (PARs) was detected byin vitro vascular ring technique. The ultrastructure of pulmonary artery wall and pulmonary artery endothelial cells were observed by light microscope and scanning electron microscope. Results: ①MAP was decreased while MPAP was increased in rabbits after LPS injection, and ES animal model was established successfully. Compared with LPS group, mPAP of rabbit in LPS+NaHS group was decreased significantly (all P<0.05). ②Compared with normal control group, pulmonary artery of rabbits in LPS group had an increased contractile response to phenylephrine (PE) and a decreased relaxation response to acetylcholine (ACh) (both P<0.01); Compared with LPS group, pulmonary artery of rabbits in LPS+NaHS group had a decreased contractile response to PE and an increased relaxation response to ACh (both P<0.05). ③Under light microscope, the structure of vascular endothelial cells was continuous in the normal control group, the elastic fibers were intact in the subcutaneous layer, and the smooth muscle layer was arranged neatly. LPS can shed some of the pulmonary artery endothelial cells, break the subcutaneous elastic fibers, and disorder the smooth muscle layer structure. Compared with LPS group, the injury of pulmonary artery wall in LPS+NaHS group was ameliorated. The morphology of pulmonary artery wall was normal in NaHS group. It is showed that some endothelial cells of pulmonary artery were missing in LPS group by Scanning electron microscopy. The morphology of pulmonary artery endothelial cells in LPS+NaHS group was similar to that in the control group: slightly widened intercellular space was observed, and no cell exfoliation was observed. Conclusion: These results suggest that exogenous H2S can protect pulmonary artery endothelial cells and regulate the reactivity changes of pulmonary artery during ES, which may be one of the mechanisms reducing PAH in ES rabbits.


Assuntos
Sulfeto de Hidrogênio , Hipertensão Pulmonar , Choque Séptico , Animais , Células Endoteliais , Sulfeto de Hidrogênio/farmacologia , Lipopolissacarídeos/efeitos adversos , Artéria Pulmonar , Coelhos
19.
Ecotoxicol Environ Saf ; 241: 113815, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36068744

RESUMO

Imidacloprid (IMI) as a first-generation commercial neonicotinoid has been frequently detected in the environment in recent years. In this study, the efficient degradation of IMI in soil by a thermally activated persulfate (PS) process was investigated. The degradation efficiencies of IMI were in the range of 82-97% with the PS dosage of 10 mM, when the initial concentrations of IMI were 5-50 mg/kg in the soil. Degradation of the IMI was fitted with a pseudo-first-order kinetic model under different reaction temperatures. Inhibition effects of the common inorganic anions on the IMI degradation in the system followed the order Cl- > HCO3- > H2PO4- > NO3-. Soil pH and soil organic matter were also main factors affecting the degradation of IMI. The degradation efficiencies (64-97%) of three other typical neonicotinoids (acetamiprid, clothianidin, and dinotefuran) indicated that the thermally activated persulfate process could be used for remediation of neonicotinoid-contaminated soil. Quenching experiments indicated that the major reactive species in IMI degradation were SO4•-, O2•-, and •OH. Six degradation intermediates of IMI were inferred in the soil, and degradation pathways of IMI included hydroxylation, denitrification, C-N bond break and further oxidation.


Assuntos
Solo , Poluentes Químicos da Água , Cinética , Neonicotinoides , Nitrocompostos , Oxirredução , Sulfatos/química , Poluentes Químicos da Água/análise
20.
Zhongguo Zhong Yao Za Zhi ; 47(15): 4183-4189, 2022 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-36046909

RESUMO

This study aims to establish an ultra-high performance liquid chromatography-tandem mass spectrometry(UHPLC-MS/MS) method for determining the concentrations of triptolide(TP) in plasma and liver, and to explore the toxicokinetics of TP and the relationship between TP exposure and liver injury in C57 BL/6 mice, so as to provide reference for dissecting the toxicity mechanism of TP. The liquid chromatography was conducted with ZORBAX SB-C_(18) column(3.0 mm×100 mm, 3.5 µm) and the mobile phase of methanol-0.05 mmol·L~(-1) ammonium acetate. Electrospray ionization(ESI) and multiple reaction monitoring(MRM) mode were employed for mass spectrometry. After oral administration of TP(toxic dose 600 µg·kg~(-1)), the blood and liver tissues of the C57 BL/6 mice were collected at different time points to measure the TP concentrations in plasma and liver tissues. Furthermore, the blood biochemical indexes, including alkaline phosphatase(ALP), alanine aminotransferase(ALT), aspartate aminotransferase(AST), and total bile acid(TBA), were determined. After being processed by DAS 2.0, the experiment data showed that the TP in mice had the toxicokinetic parameters of T_(max)=5 min, C_(max)=14.38 ng·mL~(-1), t_(1/2)=0.76 h, AUC_(0-t)=5.63 h·ng·mL~(-1), MRT_(0-t)=0.56 h, and CL_(Z/F)=103.19 L·h~(-1)·kg~(-1). The trend of TP concentration in mouse liver tissue was consistent with that in plasma. The concentration of TP peaked at the time point of 5 min and then decreased until TP was completely metabolized. The plasma biochemical indexes(ALT, AST, ALP, and TBA) showed no significant changes within 3 h after TP administration. TP had high clearance rate and short residence time and did not significantly increase the blood biochemical indexes in mice. The results suggested that the exposure amount of free TP in vivo cannot directly cause liver injury, which might be caused by the binding of TP to some substances or the stimulation of inflammation and immune response.


Assuntos
Fígado , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão/métodos , Diterpenos , Compostos de Epóxi , Camundongos , Fenantrenos , Espectrometria de Massas em Tandem/métodos , Toxicocinética
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