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1.
ACS Appl Mater Interfaces ; 13(16): 18423-18431, 2021 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-33847489

RESUMO

The expression of hypoxia-inducible factor-1α (HIF-1α) is upregulated in hypoxic environments at the lesions of rheumatoid arthritis (RA), which promoted the polarization of proinflammatory M1 macrophages and inhibited the differentiation of anti-inflammatory M2 to deteriorate synovial inflammation. Since oxygen scarcity at the joints causes an imbalance of macrophages M1 and M2, herein, we designed a cyanobacteria micro-nanodevice that can be spatiotemporally controlled in vivo to continuously producing oxygen in the RA joints for the downregulation of the expression of HIF-1α, thereby reducing the amounts of M1 macrophages and inducing the polarization of M2 macrophages for chemically sensitized RA treatment. The forthputting of temperature-sensitive hydrogel guaranteed the safety of cyanobacteria micro-nanodevice in vivo. Furthermore, the oxygen produced by cyanobacteria micro-nanodevice in a sustained manner enhanced the therapeutic effect of the antirheumatic drug methotrexate (MTX) and discouraged inflammation and bone erosion at RA. This study provided a new approach for the RA treatment of spatiotemporal-controlled release of oxygen in vitro.

2.
Hear Res ; 404: 108211, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33684887

RESUMO

The cochlear implant (CI) has an effective habilitation modality for hearing-impaired children by promoting sound perception, vocalization, and language ability. However, the major challenge that remained was the lack of assessment standards for pediatric CI users, especially prelingually deaf children, to evaluate hearing rehabilitation effectiveness. In the present study, we conducted an oddball paradigm with stimuli varying in pure-tone, syllable, and tonal sounds. After implantation, we utilized cortical auditory evoked potential (CAEP) and mismatch negativity (MMN) to obtain time-domain analysis; meanwhile, the source localization was investigated to obtain spatial accuracy of the plasticity in the auditory cortex. P1 started to emerge at the third month after implantation, but its peak level was not significant until the sixth month. The temporal lobe was activated between the third and sixth months after implantation. The MMN waveform was basically normal approximately after 12 months. These results suggest that the auditory system goes through a critical period of rapid development between three and six months and enters a maturation period after 12 months. This work indicates that CAEPs are more suitable for assessing the early auditory system reconstruction, while MMN performs better in evaluating the advanced auditory function. Furthermore, source localization has proven to be an efficient tool in exploring auditory cortex plasticity, especially for pediatric CI users.

3.
Chemosphere ; 273: 129710, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33524753

RESUMO

Bio-trickling filters (BTFs) can be used to remediate pollution by volatile organic compounds such as toluene. To investigate the effect of filler voidage on pressure drop (△P), two parallel BTFs were constructed using ceramsite with different voidages (47.5% for BTF1 and 55% for BTF2) and inoculated with Fusarium fungus to purify toluene. Commutation and stagnation operations were explored as ways to relieve △P. In BTF1, commutation temporarily relieved △P and maintained it for 7 days. Implementing stagnation on the 178th day for 69 days effectively reduced the △P from 720 Pa/m to below 20 Pa/m, which was maintained for 36 days. Compared with BTF1, the filler in BTF2 effectively delayed the increase in △P for 70 days or more and ensured stable operation for as long as 174 days. High-throughput sequencing revealed that Fusarium was mainly replaced by Protoctista, Fronsecaea and other fungi in both BTFs, although there were significant differences in their microbial communities. The influences of commutation and stagnation operations on fungal evolution were more obvious in BTF2, in relation to both time and space. The results provide guidance for designing better BTFs to treat hazardous pollutants.


Assuntos
Microbiota , Compostos Orgânicos Voláteis , Reatores Biológicos , Filtração , Fungos
4.
Theranostics ; 11(5): 2395-2409, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33500732

RESUMO

Alzheimer's disease (AD) is currently ranked as the third leading cause of death for eldly people, just behind heart disease and cancer. Autophagy is declined with aging. Our study determined the biphasic changes of miR-331-3p and miR-9-5p associated with AD progression in APPswe/PS1dE9 mouse model and demonstrated inhibiting miR-331-3p and miR-9-5p treatment prevented AD progression by promoting the autophagic clearance of amyloid beta (Aß). Methods: The biphasic changes of microRNAs were obtained from RNA-seq data and verified by qRT-PCR in early-stage (6 months) and late-stage (12 months) APPswe/PS1dE9 mice (hereinafter referred to as AD mice). The AD progression was determined by analyzing Aß levels, neuron numbers (MAP2+) and activated microglia (CD68+IBA1+) in brain tissues using immunohistological and immunofluorescent staining. MRNA and protein levels of autophagic-associated genes (Becn1, Sqstm1, LC3b) were tested to determine the autophagic activity. Morris water maze and object location test were employed to evaluate the memory and learning after antagomirs treatments in AD mice and the Aß in the brain tissues were determined. Results: MiR-331-3p and miR-9-5p are down-regulated in early-stage of AD mice, whereas up-regulated in late-stage of AD mice. We demonstrated that miR-331-3p and miR-9-5p target autophagy receptors Sequestosome 1 (Sqstm1) and Optineurin (Optn), respectively. Overexpression of miR-331-3p and miR-9-5p in SH-SY5Y cell line impaired autophagic activity and promoted amyloid plaques formation. Moreover, AD mice had enhanced Aß clearance, improved cognition and mobility when treated with miR-331-3p and miR-9-5p antagomirs at late-stage. Conclusion: Our study suggests that using miR-331-3p and miR-9-5p, along with autophagic activity and amyloid plaques may distinguish early versus late stage of AD for more accurate and timely diagnosis. Additionally, we further provide a possible new therapeutic strategy for AD patients by inhibiting miR-331-3p and miR-9-5p and enhancing autophagy.

5.
Environ Pollut ; 273: 116470, 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33486248

RESUMO

From 2015 to 2017, China took strong air pollution control measures (APCMs) for coal-fired industrial boilers (CFIBs), including eliminating CFIBs, promoting clean fuels, and updating air pollution control devices (APCDs). Based on the industrial boiler's emission inventory of air pollutants, measure-specific emission reductions from 2015 to 2017 was estimated in this study. Besides, the measure-specific environmental benefits of unit emission reduction on concentration and deposition flux were systematically evaluated by WRF-CMAQ model. The total emission reductions for CFIBs of PM10, PM2.5, SO2, NOx, Hg, As, Cd, Cr and Pb from 2015 to 2017 were 1.2 Tg, 0.53 Tg, 2.06 Tg, 0.65 Tg, 37.6 tons, 179.5 tons, 17.9 tons, 1029.3 tons and 676.0 tons, respectively. Based on meteorological fields in 2017, their corresponding national population-weighted mitigated concentration was 1.8 µg m-3, 1.3 µg m-3, 3.6 µg m-3, 0.6 µg m-3 (NO2), 0.076 ng m-3, 0.37 ng m-3, 0.04 ng m-3, 1.83 ng m-3 and 2.3 ng m-3, respectively. Updating APCDs was identified as the major measure to reduce air pollutants (except NOx), accounting for more than 35% of emission reductions and mitigated concentration. Moreover, elimination was the major NOx reduction method, contributing to 55% of NOx emission reductions. The promoting of fuels, including replacement of CFIBs with gas-fired and biomass-fired industrial boilers, had higher environmental benefits for unit emission reductions. Furthermore, there were still more than 43,000 CFIBs with the capacity <10 t h-1, accounting for 14%, 21%, and 11% of total PM2.5, SO2, and NOX emissions for CFIBs in 2017; meanwhile, 20% and 59% of CFIBs did not install flue gas desulfurization and denitrification devices, respectively. Therefore, it is recommended to give priority to phase out CFIBs with capacity <10 t h-1 and APCDs updating for larger capacity CFIBs in the future.

6.
Sci Total Environ ; : 143733, 2020 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-33279183

RESUMO

Coal-fired industrial boilers (CFIBs) are a significant source of trace metals (TMs) emissions, due to its large number and widespread industry application. In this study, a highly resolved of county-based atmospheric emission inventory of Hg, As, Cd, Cr and Pb for Chinese CFIBs in 2017 is established firstly based on integrated source-specific information of both activity level and air pollution control devices (APCDs) from ~61,000 CFIBs in mainland China. Our results estimated that the total emissions of Hg, As, Cd, Cr and Pb from national CFIBs in 2017 were about 25.46, 115.33, 7.04, 371.40, and 589.76 t, respectively. Hg0 was the majority species of atmospheric Hg, accounting for 71.5% of the total Hg emission. The peak emission intensities of five TMs were mainly concentrated in northern and eastern region of China due to its large demand of coal consumption for winter heating, broad economic activity, as well as high population density. Monthly emission characteristics of TMs exhibited seasonal peak. The overall uncertainties of the newly updated emission inventory were estimated at the ranges of -42.0%-45.5%. Generally, TMs emissions from Chinese CFIBs were effectively controlled through implementing energy substitution, APCDs upgrading, and ultra-low emission (ULE) retrofitting in different regions of China, which contributed to 18.8%-29.4% of five TMs emission reductions. We believe that our highly resolved county-level emission inventory will be comprehensively explored the current tempo-spatial emission characteristics of atmospheric TMs from Chinese CFIBs and the forecast results will be useful for developing effective emission control programs for policy makers in the county levels and improving the regional air quality in the future.

7.
Autophagy ; : 1-17, 2020 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-33143524

RESUMO

Senile osteoporosis (OP) is often concomitant with decreased autophagic activity. OPTN (optineurin), a macroautophagy/autophagy (hereinafter referred to as autophagy) receptor, is found to play a pivotal role in selective autophagy, coupling autophagy with bone metabolism. However, its role in osteogenesis is still mysterious. Herein, we identified Optn as a critical molecule of cell fate decision for bone marrow mesenchymal stem cells (MSCs), whose expression decreased in aged mice. Aged mice revealed osteoporotic bone loss, elevated senescence of MSCs, decreased osteogenesis, and enhanced adipogenesis, as well as optn- / - mice. Importantly, restoring Optn by transplanting wild-type MSCs to optn- / - mice or infecting optn- / - mice with Optn-containing lentivirus rescued bone loss. The introduction of a loss-of-function mutant of OptnK193R failed to reestablish a bone-fat balance. We further identified FABP3 (fatty acid binding protein 3, muscle and heart) as a novel selective autophagy substrate of OPTN. FABP3 promoted adipogenesis and inhibited osteogenesis of MSCs. Knockdown of FABP3 alleviated bone loss in optn- / - mice and aged mice. Our study revealed that reduced OPTN expression during aging might lead to OP due to a lack of FABP3 degradation via selective autophagy. FABP3 accumulation impaired osteogenesis of MSCs, leading to the occurrence of OP. Thus, reactivating OPTN or inhibiting FABP3 would open a new avenue to treat senile OP. Abbreviations: ADIPOQ: adiponectin, C1Q and collagen domain containing; ALPL: alkaline phosphatase, liver/bone/kidney; BGLAP/OC/osteocalcin: bone gamma carboxyglutamate protein; BFR/BS: bone formation rate/bone surface; CALCOCO2/NDP52: calcium binding and coiled-coil domain 2; CDKN1A/p21: cyclin-dependent kinase inhibitor 1A; CDKN2A/p16: cyclin dependent kinase inhibitor 2A; CDKN2B/p15: cyclin dependent kinase inhibitor 2B; CEBPA: CCAAT/enhancer binding protein (C/EBP), alpha; COL1A1: collagen, type I, alpha 1; Ct. BV/TV: cortical bone volume fraction; Ct. Th: cortical thickness; Es. Pm: endocortical perimeter; FABP4/Ap2: fatty acid binding protein 4, adipocyte; H2AX: H2A.X variant histone; HE: hematoxylin and eosin; MAP1LC3B: microtubule-associated protein 1 light chain 3 beta; MAR: mineral apposition rate; MSCs: bone marrow mesenchymal stem cells; NBR1: NBR1, autophagy cargo receptor; OP: osteoporosis; OPTN: optineurin; PDB: Paget disease of bone; PPARG: peroxisome proliferator activated receptor gamma; Ps. Pm: periosteal perimeter; qRT-PCR: quantitative real-time PCR; γH2AX: Phosphorylation of the Serine residue of H2AX; ROS: reactive oxygen species; RUNX2: runt related transcription factor 2; SA-GLB1: senescence-associated (SA)-GLB1 (galactosidase, beta 1); SP7/Osx/Osterix: Sp7 transcription factor 7; SQSTM1/p62: sequestosome 1; TAX1BP1: Tax1 (human T cell leukemia virus type I) binding protein 1; Tb. BV/TV: trabecular bone volume fraction; Tb. N: trabecular number; Tb. Sp: trabecular separation; Tb. Th: trabecular thickness; µCT: micro computed tomography.

9.
Cardiovasc Diagn Ther ; 10(5): 1184-1191, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33224742

RESUMO

Background: Left ventricular remodeling is the basic pathological mechanism of heart failure following acute myocardial infarction (AMI). Determining sensitive indexes for the early prediction of ventricular remodeling is important for the prevention of heart failure. This study aims to investigate the value of serum TIMP-3, CA125, and NT-proBNP in predicting ventricular remodeling in patients with heart failure following AMI. Methods: From May 2017 to May 2018, 93 patients with heart failure following AMI were enrolled in the study. The participants were divided into two groups: the ventricular remodeling group (n=51) and the non-ventricular remodeling group (n=42). In addition, 47 healthy subjects who underwent physical examinations in the same period were enrolled as controls. Serum TIMP-3, CA125, and NT-proBNP were measured, in addition to the left ventricular wall thickness (LVWT) and left ventricular mass index (LVMI). The correlation of serum TIMP-3, CA125, and NT-proBNP with the LVWT and LVMI was analyzed, and its value in predicting ventricular remodeling was evaluated. Results: Serum TIMP-3 level was lower (P<0.05) and CA125 and NT-proBNP levels were higher (P<0.05) in both the ventricular remodeling and non-ventricular remodeling groups compared with the control group. Furthermore, the serum TIMP-3 level was lower in the ventricular remodeling group compared with the non-ventricular remodeling group (P<0.05), while the levels of CA125 and NT-proBNP were higher in the ventricular remodeling group compared with the non-ventricular remodeling group (P<0.05). The serum TIMP-3 level was negatively correlated with the LVWT and LVMI, while serum CA125 and NT-proBNP levels were positively correlated with the LVWT and LVMI, respectively. The area under the receiver operating characteristic curve of the combination of serum TIMP-3, CA125, and NT-proBNP levels in predicting ventricular remodeling was 0.850, and the prediction sensitivity and specificity were 74.51% and 87.71%, respectively. Conclusions: The combination of serum TIMP-3, CA125, and NT-proBNP can improve the sensitivity and specificity of predicting ventricular remodeling and can aid in the early prevention and treatment of heart failure.

10.
Sci Adv ; 6(43)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33097529

RESUMO

Poor wound healing after diabetes or extensive burn remains a challenging problem. Recently, we presented a physical approach to fabricate ultrasmall silver particles from Ångstrom scale to nanoscale and determined the antitumor efficacy of Ångstrom-scale silver particles (AgÅPs) in the smallest size range. Here we used the medium-sized AgÅPs (65.9 ± 31.6 Å) to prepare carbomer gel incorporated with these larger AgÅPs (L-AgÅPs-gel) and demonstrated the potent broad-spectrum antibacterial activity of L-AgÅPs-gel without obvious toxicity on wound healing-related cells. Induction of reactive oxygen species contributed to L-AgÅPs-gel-induced bacterial death. Topical application of L-AgÅPs-gel to mouse skin triggered much stronger effects than the commercial silver nanoparticles (AgNPs)-gel to prevent bacterial colonization, reduce inflammation, and accelerate diabetic and burn wound healing. L-AgÅPs were distributed locally in skin without inducing systemic toxicities. This study suggests that L-AgÅPs-gel represents an effective and safe antibacterial and anti-inflammatory material for wound therapy.

11.
Dis Model Mech ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33033107

RESUMO

Improving revascularization is one of the major measures in fracture treatment. Moderate local inflammation triggers angiogenesis, whereas systemic inflammation hampers angiogenesis. Previous studies showed that Akkermansia muciniphila (A. muc), a gut probiotic, ameliorates systemic inflammation by tightening intestinal barrier. In this study, fractured mice intragastrically administrated with A. muc were found to display better fracture healing than mice treated with vehicle. Notably, more preosteclasts positive for platelet-derived growth factor-BB (PDGF-BB) were induced by A. muc at 2 weeks post fracture, coinciding with increased formation of type H vessels, a specific vessel subtype that couples angiogenesis and osteogenesis and can be stimulated by PDGF-BB. Moreover, A. muc treatment significantly reduced gut permeability and inflammation at early stage. Dextran Sulfate Sodium (DSS) was used to disrupt the gut barrier to determine the role of gut barrier in fracture healing and whether A. muc still can stimulate bone fracture healing. As expected, A. muc evidently improved gut barrier, reduced inflammation, and restored the impaired bone healing and angiogenesis in DSS-treated mice. Our results suggest that A. muc reduces intestinal permeability and alleviates inflammation, which probably induces more PDGF-BB positive preosteoclasts and type H vessel formation in callus, thereby promoting fracture healing. This study provides the evidences about the involvement of type H vessels in fracture healing and suggests the potential of A. muc as a promising strategy for bone healing.

12.
Cancer Commun (Lond) ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33119215

RESUMO

Altered metabolism is a hallmark of cancer, and the reprogramming of energy metabolism has historically been considered a general phenomenon of tumors. It is well recognized that long noncoding RNAs (lncRNAs) regulate energy metabolism in cancer. However, lncRNA-mediated posttranslational modifications and metabolic reprogramming are unclear at present. In this review, we summarized the current understanding of the interactions between the alterations in cancer-associated energy metabolism and the lncRNA-mediated posttranslational modifications of metabolic enzymes, transcription factors, and other proteins involved in metabolic pathways. In addition, we discuss the mechanisms through which these interactions contribute to tumor initiation and progression, and the key roles and clinical significance of functional lncRNAs. We believe that an in-depth understanding of lncRNA-mediated cancer metabolic reprogramming can help to identify cellular vulnerabilities that can be exploited for cancer diagnosis and therapy.

13.
Nucleic Acids Res ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32990749

RESUMO

T cells and the T-cell receptor (TCR) repertoire play pivotal roles in immune response and immunotherapy. TCR sequencing (TCR-Seq) technology has enabled accurate profiling TCR repertoire and currently a large number of TCR-Seq data are available in public. Based on the urgent need to effectively re-use these data, we developed TCRdb, a comprehensive human TCR sequences database, by a uniform pipeline to characterize TCR sequences on TCR-Seq data. TCRdb contains more than 277 million highly reliable TCR sequences from over 8265 TCR-Seq samples across hundreds of tissues/clinical conditions/cell types. The unique features of TCRdb include: (i) comprehensive and reliable sequences for TCR repertoire in different samples generated by a strict and uniform pipeline of TCRdb; (ii) powerful search function, allowing users to identify their interested TCR sequences in different conditions; (iii) categorized sample metadata, enabling comparison of TCRs in different sample types; (iv) interactive data visualization charts, describing the TCR repertoire in TCR diversity, length distribution and V-J gene utilization. The TCRdb database is freely available at http://bioinfo.life.hust.edu.cn/TCRdb/ and will be a useful resource in the research and application community of T cell immunology.

14.
Abdom Radiol (NY) ; 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32940755

RESUMO

PURPOSE: To establish and validate two predictive radiomics models for preoperative prediction of lymph node metastases (LNMs) and tumor deposits (TDs) respectively in rectal cancer (RC) patients. METHODS: A total of 139 RC patients (98 in the training cohort and 41 in the validation cohort) were enrolled in the present study. High-resolution magnetic resonance images (HRMRI) were retrieved for tumor segmentation and feature extraction. HRMRI findings of RC were assessed by three experienced radiologists. Two radiomics nomograms were established by integrating the clinical risk factors, HRMRI findings and radiomics signature. RESULTS: The predictive nomogram of LNMs showed good predictive performance (area under the curve [AUC], 0.90; 95% confidence interval [CI] 0.83-0.96) which was better than clinico-radiological (AUC, 0.83; 95% CI 0.74-0.93; Delong test, p = 0.017) or radiomics signature-only model (AUC, 0.77; 95% CI 0.67-0.86; Delong test, p = 0.003) in training cohort. Application of the nomogram in the validation cohort still exhibited good performance (AUC, 0.87; 95% CI 0.76-0.98). The accuracy, sensitivity and specificity of the combined model in predicting LNMs was 0.86,0.79 and 0.91 in training cohort and 0.83,0.85 and 0.82 in validation cohort. As for TDs, the predictive efficacy of the nomogram (AUC, 0.82; 95% CI 0.71-0.93) was not significantly higher than radiomics signature-only model (AUC, 0.80; 95% CI 0.69-0.92; Delong test, p = 0.71). Radiomics signature-only model was adopted to predict TDs with accuracy=0.76, sensitivity=0.72 and specificity=0.94 in training cohort and 0.68, 0.62 and 0.97 in validation cohort. CONCLUSION: HRMRI-based radiomics models could be helpful for the prediction of LNMs and TDs preoperatively in RC patients.

15.
Biomed Pharmacother ; 131: 110721, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32920517

RESUMO

Sarcopenia is a syndrome characterized by progressive systemic muscle loss and decreased function. The loss of systemic muscle mass and decreased function after stroke can't be explained by brain injury alone, and it is considered to be a kind of secondary sarcopenia, which is called stroke-related sarcopenia. More and more evidence shows that stroke-related sarcopenia can promote the occurrence and development of sarcopenia through a variety of pathogenesis, such as immobilization, impaired feeding, sympathetic activation, inflammation and denervation. Post-stroke disability brings difficulties to the screening and diagnosis of sarcopenia. Simple and easy rehabilitation scores and clinical tests can be used for the determination of body function under specific conditions of stroke, as well as for the screening stroke-related sarcopenia. At present, there is still no particularly effective way to stop its progress,however, the combination of rehabilitation exercise, nutrition supply and drugs may delay or even prevent the development of stroke-related sarcopenia. This article reviews the latest progress in the pathogenesis, screening, evaluation and treatment of stroke-related sarcopenia to provide reference for clinical treatment and rehabilitation of stroke.

16.
Allergy ; 2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32810290

RESUMO

BACKGROUND: Atopy, the overall tendency to become sensitized to an allergen, is heritable but seldom ascribed to mutations within specific genes. Atopic individuals develop abnormally elevated IgE responses to immunization with potential allergens. To gain insight into the genetic causes of atopy, we carried out a forward genetic screen for atopy in mice. METHODS: We screened mice carrying homozygous and heterozygous N-ethyl-N-nitrosourea (ENU)-induced germline mutations for aberrant antigen-specific IgE and IgG1 production in response to immunization with the model allergen papain. Candidate genes were validated by independent gene mutation. RESULTS: Of 31 candidate genes selected for investigation, the effects of mutations in 23 genes on papain-specific IgE or IgG1 were verified. Among the 20 verified genes influencing the IgE response, eight were necessary for the response, while 12 repressed IgE. Nine genes were not previously implicated in the IgE response. Fifteen genes encoded proteins contributing to IgE class switch recombination or B-cell receptor signaling. The precise roles of the five remaining genes (Flcn, Map1lc3b, Me2, Prkd2, and Scarb2) remain to be determined. Loss-of-function mutations in nine of the 12 genes limiting the IgE response were dominant or semi-dominant for the IgE phenotype but did not cause immunodeficiency in the heterozygous state. Using damaging allele frequencies for the corresponding human genes and in silico simulations (Monte Carlo) of undiscovered atopy mutations, we estimated the percentage of humans with heterozygous atopy risk mutations. CONCLUSIONS: Up to 37% of individuals may be heterozygous carriers for at least one dominant atopy risk mutation.

17.
Phytomedicine ; 77: 153274, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32771537

RESUMO

BACKGROUND: Astragali Radix (AR), a common Traditional Chinese Medicine (TCM), is commonly used for treating nephrotic syndrome (NS) in China. At present, the research on the efficacy of AR against NS is relative clearly, but there are fewer researches on the mechanism. PURPOSE: The aim of this study was to evaluate the potential beneficial effects of AR in an adriamycin-induced nephropathy rat model, as well as investigate the possible mechanisms of action and potential lipid biomarkers. METHODS: In this work, a rat model of NS was established by two injections of ADR (3.5 + 1 mg/kg) into the tail vein. The potential metabolites and targets involved in the anti-NS effects of AR were predicted by lipidomics coupled with the network pharmacology approach, and the crucial metabolite and protein were further validated by western blotting and ELISA. RESULTS: The results showed that 22 metabolites such as l-carnitine, LysoPC (20:3), and SM (d18:1/16:0) were associated with renal injury. Moreover, SMPD1, CPT1A and LCAT were predicted as lipids linked targets of AR against NS, whilst glycerophospholipid, sphingolipid and fatty acids metabolism were involved as key pathways of AR against NS. Besides, AR could play a critical role in NS by improving oxidative stress, inhibiting apoptosis and reducing inflammation. Interestingly, our results indicated that key metabolite l-carnitine and target CPT1 were one of the important metabolites and targets for AR to exert anti-NS effects. CONCLUSION: In summary, this study offered a new understanding of the protection mechanism of AR against NS by network pharmacology and lipidomic method.

18.
World J Clin Cases ; 8(12): 2473-2483, 2020 Jun 26.
Artigo em Inglês | MEDLINE | ID: mdl-32607324

RESUMO

BACKGROUND: Multiple system atrophy (MSA) is a serious progressive neurodegenerative disease. Early diagnosis of MSA is very difficult, and diagnostic biomarkers are limited. Growth differentiation factor 15 (GDF15) is involved in the differentiation and progression of the central nervous system, and is widely distributed in peripheral blood, which may be a novel biomarker for MSA. AIM: To determine serum GDF15 levels, related factors and their potential diagnostic value in MSA patients, compared with Parkinson's disease (PD) patients and healthy controls. METHODS: A case-control study was conducted, including 49 MSA patients, 50 PD patients and 50 healthy controls. Serum GDF15 levels were measured by human enzyme-linked immunosorbent assay, and the differences between the MSA, PD and control groups were analyzed. Further investigations were performed in different MSA subgroups according to age of onset, sex, clinical subtypes, diagnostic criteria, and disease duration. Receiver-operating characteristic curve analysis was used to evaluate the diagnostic value of GDF15, especially for the differential diagnosis between MSA and PD. RESULTS: Serum GDF15 levels were significantly higher in MSA patients than in PD patients and healthy controls (P = 0.000). Males and those with a disease duration of more than three years showed higher serum GDF15 levels (P = 0.043 and 0.000; respectively). Serum GDF15 levels may be a potential diagnostic biomarker for MSA patients compared with healthy controls and PD patients (cutoff: 470.42 pg/mL, sensitivity: 85.7%, specificity: 88.0%; cutoff: 1075.91 pg/mL, sensitivity: 51.0%, specificity: 96.0%; respectively). CONCLUSION: Serum GDF15 levels are significantly higher in MSA patients and provide suggestions on the etiology of MSA.

19.
Huan Jing Ke Xue ; 41(4): 1561-1572, 2020 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-32608661

RESUMO

Black carbon (BC) was measured at Chengdu from December 1, 2017, to November 30, 2018, using a seven-channel aethalometer (AE-33). The variation characteristics of BC were obtained. BC sources were explored based on the aethalometer model and a hybrid single particle Lagrangian integrated trajectory model (Hysplit-4). The results showed the BC concentration was the highest in the winter (8.18 µg·m-3) with the monthly mean of 11.11 µg·m-3 peaking in December, followed by the spring (5.11 µg·m-3) and autumn (3.91 µg·m-3), and was the lowest in summer (3.28 µg·m-3) with the lowest monthly mean of 2.30 µg·m-3 in July. The annual average concentration of BC was 5.26 µg·m-3 with a standard deviation of 4.27 µg·m-3. The diurnal variations of BC showed typical bimodal patterns in four seasons mainly due to the influence of the boundary layer and traffic rush. The source apportionment of BC showed that the liquid fuel (e.g., vehicle emission) had higher contribution to total BC concentration during all seasons (ranging from 69% in winter to 82% in summer) than solid fuel (e.g., coal and biomass combustion). The contribution of liquid fuel to the total BC was higher in summer, while solid fuel had a higher contribution in winter. The diurnal cycles of BC source apportionment demonstrated that the contribution of liquid fuel increased in the rush hours. The results of potential source contribution function and concentration weighted trajectory showed that the potential sources of BC in Chengdu were slightly different in different seasons and were mainly affected by the different air mass sources. However, the main potential source regions were the surrounding areas of Chengdu and the areas between Chengdu and Chongqing (the Chuanyu City group). The mass contribution to the BC in Chengdu was high in the region where liquid fuel most affected the total BC. Additionally, the southern part of Shaanxi and the southern part of Gansu were also potential sources of BC, and in Summer, some regions in Guangxi and Guizhou could become the source regions of BC in Chengdu.

20.
Theranostics ; 10(17): 7710-7729, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32685015

RESUMO

Osteosarcoma is a common malignant bone cancer easily to metastasize. Much safer and more efficient strategies are still needed to suppress osteosarcoma growth and lung metastasis. We recently presented a pure physical method to fabricate Ångstrom-scale silver particles (AgÅPs) and determined the anti-tumor efficacy of fructose-coated AgÅPs (F-AgÅPs) against lung and pancreatic cancer. Our study utilized an optimized method to obtain smaller F-AgÅPs and aimed to assess whether F-AgÅPs can be used as an efficient and safe agent for osteosarcoma therapy. We also investigated whether the induction of apoptosis by altering glucose metabolic phenotype contributes to the F-AgÅPs-induced anti-osteosarcoma effects. Methods: A modified method was developed to prepare smaller F-AgÅPs. The anti-tumor, anti-metastatic and pro-survival efficacy of F-AgÅPs and their toxicities on healthy tissues were compared with that of cisplatin (a first-line chemotherapeutic drug for osteosarcoma therapy) in subcutaneous or orthotopic osteosarcoma-bearing nude mice. The pharmacokinetics, biodistribution and excretion of F-AgÅPs were evaluated by testing the levels of silver in serum, tissues, urine and feces of mice. A series of assays in vitro were conducted to assess whether the induction of apoptosis mediates the killing effects of F-AgÅPs on osteosarcoma cells and whether the alteration of glucose metabolic phenotype contributes to F-AgÅPs-induced apoptosis. Results: The newly obtained F-AgÅPs (9.38 ± 4.11 nm) had good stability in different biological media or aqueous solutions and were more effective than cisplatin in inhibiting tumor growth, improving survival, attenuating osteolysis and preventing lung metastasis in osteosarcoma-bearing nude mice after intravenous injection, but were well tolerated in normal tissues. One week after injection, about 68% of F-AgÅPs were excreted through feces. F-AgÅPs induced reactive oxygen species (ROS)-dependent apoptosis of osteosarcoma cells but not normal cells, owing to their ability to selectively shift glucose metabolism of osteosarcoma cells from glycolysis to mitochondrial oxidation by inhibiting pyruvate dehydrogenase kinase (PDK). Conclusion: Our study suggests the promising prospect of F-AgÅPs as a powerful selective anticancer agent for osteosarcoma therapy.

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