Publications by authors named "Xin Yao"

458 Publications

Transparent ultra-wideband double-resonance-layer metamaterial absorber designed by a semiempirical optimization method.

Opt Express 2021 Jun;29(12):18446-18457

In this study, a transparent ultra-wideband double-resonance-layer absorber was designed using a semiempirical optimization method. In this method, an equivalent circuit model, genetic algorithm, and parameter fitting are employed to reduce the computation time and improve the design flexibility. Simulations and measurements show that the as-designed absorber can achieve ultrawide microwave absorption in the range of 2.00 to 11.37 GHz with a fractional bandwidth of 140.2%. Furthermore, electric field and surface current distributions show that the broad bandwidth was derived from the good matching of the absorption peaks in the two resonance layers. In addition, the target waveband of the as-designed absorber covered the wavebands of WiFi and radio-frequency identification, as well as part of the 5G waveband. This makes the proposed absorber a good candidate for daily electromagnetic pollution reduction.
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http://dx.doi.org/10.1364/OE.427318DOI Listing
June 2021

The bacterial community composition and its environmental drivers in the rivers around eutrophic Chaohu Lake, China.

BMC Microbiol 2021 Jun 14;21(1):179. Epub 2021 Jun 14.

Taihu Laboratory for Lake Ecosystem Research, State Key Laboratory of Lake Science and Environment, Nanjing Institute of Geography and Limnology, Chinese Academy of Sciences, 210008, Nanjing, China.

Background: Bacterial community play a key role in environmental and ecological processes in river ecosystems. Rivers are used as receiving body for treated and untreated urban wastewaters that brings high loads of sewage and excrement bacteria. However, little is known about the bacterial community structure and functional files in the rivers around the eutrophic Chaohu Lake, the fifth largest freshwater lake in China, has been subjected to severe eutrophication and cyanobacterial blooms over the past few decades. Therefore, understanding the taxonomic and functional compositions of bacterial communities in the river will contribute to understanding aquatic microbial ecology. The main aims were to (1) examine the structure of bacterial communities and functional profiles in this system; (2) find the environmental factors of bacterial community variations.

Results: We studied 88 sites at rivers in the Chaohu Lake basin, and determined bacterial communities using Illumina Miseq sequencing of the 16 S rRNA gene, and predicted functional profiles using PICRUSt2. A total of 3,390,497 bacterial 16 S rRNA gene sequences were obtained, representing 17 phyla, and 424 genera; The dominant phyla present in all samples were Bacteroidetes (1.4-82.50 %), followed by Proteobacteria (12.6-97.30 %), Actinobacteria (0.1-17.20 %). Flavobacterium was the most numerous genera, and accounted for 0.12-80.34 % of assigned 16 S reads, followed by Acinetobacter (0.33-49.28 %). Other dominant bacterial genera including Massilia (0.06-25.40 %), Psychrobacter (0-36.23 %), Chryseobacterium (0.01-22.86 %), Brevundimonas (0.01-12.82 %), Pseudomonas (0-59.73 %), Duganella (0.08-23.37 %), Unidentified Micrococcaceae (0-8.49 %). The functional profiles of the bacterial populations indicated an relation with many human diseases, including infectious diseases. Overall results, using the β diversity measures, coupled with heatmap and RDA showed that there were spatial variations in the bacterial community composition at river sites, and Chemical oxygen demand (COD) and (NH )were the dominant environmental drivers affecting the bacterial community variance.

Conclusions: The high proportion of the opportunistic pathogens (Acinetobacter, Massilia, Brevundimonas) indicated that the discharge of sewage without adequate treatment into the rivers around Chaohu Lake. We propose that these bacteria could be more effective bioindicators for long-term sewage monitoring in eutrophic lakes.
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http://dx.doi.org/10.1186/s12866-021-02252-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201733PMC
June 2021

Research Progress on Phytopathogenic Fungi and Their Role as Biocontrol Agents.

Front Microbiol 2021 28;12:670135. Epub 2021 May 28.

College of Plant Protection, Gansu Agricultural University, Lanzhou, China.

Phytopathogenic fungi decrease crop yield and quality and cause huge losses in agricultural production. To prevent the occurrence of crop diseases and insect pests, farmers have to use many synthetic chemical pesticides. The extensive use of these pesticides has resulted in a series of environmental and ecological problems, such as the increase in resistant weed populations, soil compaction, and water pollution, which seriously affect the sustainable development of agriculture. This review discusses the main advances in research on plant-pathogenic fungi in terms of their pathogenic factors such as cell wall-degrading enzymes, toxins, growth regulators, effector proteins, and fungal viruses, as well as their application as biocontrol agents for plant pests, diseases, and weeds. Finally, further studies on plant-pathogenic fungal resources with better biocontrol effects can help find new beneficial microbial resources that can control diseases.
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http://dx.doi.org/10.3389/fmicb.2021.670135DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8192705PMC
May 2021

Characterizing variations in dissolved organic matter (DOM) properties in Nansi Lake: a typical macrophytes-derived lake in northern China.

Environ Sci Pollut Res Int 2021 Jun 12. Epub 2021 Jun 12.

School of Environment and Planning, Liaocheng University, Road 1, Liaocheng, 252000, Hunan, China.

Nansi Lake is the largest lake along the eastern route of China's South-to-North Water Diversion Project (SNWDP). It is divided into the upper lake and the lower lake by a dam. By using UV-Vis spectroscopy, synchronous fluorescence (SF) spectroscopy, excitation-emission matrix and parallel factor analysis (EEM-PARAFAC), spatial, and temporal differences in the properties of dissolved organic matter (DOM) were found in the 2 areas of Nansi Lake under different hydrological conditions. A total of 5 fluorescence components were obtained by EEM-PARAFAC, which included 3 humic-like components (C1-C3) and 2 protein-like components (C4 and C5). On the spatial scale, the fluorescence intensities (F) of humic-like substances and the ratio of the fluorescence intensity of humic-like components to the total fluorescence intensity (%F) and degree of humification (HIX) in the upper lake were higher than those in the lower lake. This indicated the strong contributions of terrestrial sources to the upper lake, while DOM properties in the lower lake were more endogenous than those in the upper lake. On the temporal scale, protein-like substances played a more important role in DOM properties in April (F=0.72±0.03 in the upper lake and 1.84±0.13 in the lower lake) and July (F=1.10±0.05 in the upper lake and 1.49±0.04 in the lower lake) than in October. This result might be related to the water transfer of the eastern route of the SNWDP and to the death of submerged plants. However, the contents of humic-like substances (ranging from 55.61±1.23% to 66.56±0.58% for the upper lake and 29.98±1.56% to 61.98±0.99% for the lower lake) and degree of humification (from 2.23±0.06 to 3.10±0.05 for the upper lake and 1.06±0.05 to 2.62±0.08 for the lower lake) in Nansi Lake showed an increasing trend from April to October. In addition, significant correlations and good linear relationships between humic-like components, a, and DOC in the 3 months reflected the continuous contribution of humic-like substances to DOM properties in Nansi Lake. Rapid changes in the fluorescence signal were largely dependent on changes in water quality. The fluorescence signal could be a tool for the management of water quality in Nansi Lake.
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http://dx.doi.org/10.1007/s11356-021-14266-xDOI Listing
June 2021

Mechanisms and biomarkers of airway epithelial cell damage in asthma: a review.

Clin Respir J 2021 Jun 7. Epub 2021 Jun 7.

Department of Respiratory and Critical Care Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Bronchial asthma is a heterogeneous disease with complex pathological mechanisms representing different phenotypes, including severe asthma. The airway epithelium is a major site of complex pathological changes in severe asthma due, in part, to activation of inflammatory and immune mechanisms in response to noxious agents. Current imaging procedures are unable to accurately measure epithelial and airway remodeling. Damage of airway epithelial cells occurs is linked to specific phenotypes and endotypes which provides an opportunity for the identification of biomarkers reflecting epithelial, and airway, remodeling. Identification of patients with more severe epithelial disruption using biomarkers may also provide personalized therapeutic opportunities and/or markers of successful therapeutic intervention. Here, we review the evidence for ongoing epithelial cell dysregulation in the pathogenesis of asthma, the sentinel role of the airway epithelium and how understanding these molecular mechanisms provides the basis for the identification of candidate biomarkers for asthma prediction, prevention, diagnosis, treatment and monitoring.
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http://dx.doi.org/10.1111/crj.13407DOI Listing
June 2021

Plastid NDH Pseudogenization and Gene Loss in a Recently Derived Lineage from the Largest Hemiparasitic Plant Genus Pedicularis (Orobanchaceae).

Plant Cell Physiol 2021 May 28. Epub 2021 May 28.

Center for Integrative Conservation, Xishuangbanna Tropical Botanical Garden, Chinese Academy of Sciences, Mengla, Yunnan 666303, China.

The plastid genome (plastome) is highly conserved in both gene order and content and has a lower mutation rate than the nuclear genome. However, the plastome is more variable in heterotrophic plants. To date, most such studies have investigated just a few species or only holoheterotrophic groups, and few have examined plastome evolution in recently derived lineages at an early stage of transition from autotrophy to heterotrophy. In this study, we investigated the evolutionary dynamics of plastomes in the monophyletic and recently derived Pedicularis sect. Cyathophora (Orobanchaceae) . We obtained 22 new plastomes, 13 from the six recognized species of section Cyathophora, six from hemiparasitic relatives, and three from autotrophic relatives. Comparative analyses of gene content, plastome structure, and selection pressure showed dramatic differences among species in section Cyathophora and in Pedicularis as a whole. In comparison with autotrophic relatives and other Pedicularis spp., we found that the IR region in section Cyathophora had expansions to the SSC region, with a large expansion event and two independent contraction events. Moreover, NDH, accD, and ccsA have lost function multiple times with the function of accD being replaced by nuclear copies of an accD-like gene in Pedicularis spp. The ccsA and ndhG genes may have evolved under selection in association with IR expansion/contraction events. This study is the first to report high plastome variation in a recently derived lineage of hemiparasitic plants, and therefore provides evidence for plastome evolution in the transition from autotrophy to heterotrophy.
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http://dx.doi.org/10.1093/pcp/pcab074DOI Listing
May 2021

A novel diagnostic signature based on three circulating exosomal mircoRNAs for chronic obstructive pulmonary disease.

Exp Ther Med 2021 Jul 3;22(1):717. Epub 2021 May 3.

Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.

Exosomal microRNAs (exo-miRNAs or miRs) have demonstrated diagnostic value in various diseases. However, their diagnostic value in chronic obstructive pulmonary disease (COPD) has yet to be fully established. The purpose of the present study was to screen differentially expressed exo-miRNAs in the plasma of patients with COPD and healthy individuals and to evaluate their potential diagnostic value in COPD. Differentially expressed exo-miRNAs in the plasma of patients with COPD and controls were identified using high-throughput sequencing and confirmed using reverse transcription-quantitative PCR (RT-qPCR). Bioinformatics analysis was then performed to predict the function of the selected exo-miRNAs and their target genes in COPD. After a network model was constructed, linear regression analysis was performed to determine the association between exo-miRNA expression and the clinical characteristics of subjects in a validated cohort (46 COPD cases; 34 matched healthy controls). Receiver operating characteristic curve was subsequently plotted to test the diagnostic value of the candidate biomarkers. The top 20 significantly aberrantly expressed COPD-associated exo-miRNAs were verified using RT-qPCR. Of these, nine were then selected for subsequent analysis, five of which were found to be upregulated (miR-23a, miR-1, miR-574, miR-152 and miR-221) and four of which were downregulated (miR-3158, miR-7706, miR-685 and miR-144). The results of Gene Ontology and KEGG pathway analysis revealed that these miRNAs were mainly involved in certain biological functions, such as metabolic processes, such as galactose metabolism and signaling pathways (PI3K-AKT) associated with COPD. The expression levels of three exo-miRNAs (miR-23a, miR-221 and miR-574) were found to be negatively associated with the forced expiratory volume in the 1st second/forced vital capacity. Furthermore, the area under the curve values of the three exo-miRNAs (miR-23a, miR-221 and miR-574) for COPD diagnosis were 0.776 [95% confidence interval (CI), 0.669-0.882], 0.688 (95% CI, 0.563-0.812) and 0.842 (95% CI, 0.752-0.931), respectively. In conclusion, the three circulating exosomal miRNAs (miR-23a, miR-221 and miR-574) may serve as novel circulating biomarkers for the diagnosis of COPD. These results may also enhance our understanding and provide novel potential treatment options for patients with COPD.
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http://dx.doi.org/10.3892/etm.2021.10149DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8120666PMC
July 2021

Tunable and transparent broadband metamaterial absorber with water-based substrate for optical window applications.

Nanoscale 2021 Apr;13(16):7831-7837

Key Laboratory of Materials for High-Power Laser, Shanghai Institute of Optics and Fine Mechanics, Chinese Academy of Sciences, Shanghai, 201800, China. and Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310024, China and CAS Center for Excellence in Ultra-intense Laser Science, Shanghai 201800, China.

A tunable and transparent metamaterial absorber (MMA) with a water-based substrate is presented, with high optical transparency and broadband microwave absorptivity. In the material structure, indium-tin-oxide (ITO) films are included as the resonant pattern and reflective layers, and distilled water is combined with polymethyl methacrylate (PMMA) to produce the dielectric substrate. By effectively designing its structural parameters, the proposed absorber achieves >90% absorptivity, covering an ultrawide frequency range of 5.8-16.2 GHz, while the average optical transmittance is ∼70.18% over a wavelength range of 400-800 nm. Moreover, owing to a specific design feature, the absorber has high polarization insensitivity and wide-incident-angle stability for transverse electric (TE) and transverse magnetic (TM) polarization waves. Furthermore, the absorption properties of the absorber can be further tuned by controlling the thickness of the water substrate. Both numerical simulations and experimental measurements demonstrate the excellent performance of the device, showing its strong potential for use in optical windows within military and medical equipment.
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http://dx.doi.org/10.1039/d0nr08640aDOI Listing
April 2021

The synergistic antitumor activity of 3-(2-nitrophenyl) propionic acid-paclitaxel nanoparticles (NPPA-PTX NPs) and anti-PD-L1 antibody inducing immunogenic cell death.

Drug Deliv 2021 Dec;28(1):800-813

Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University, Beijing, People's Republic of China.

Cancer immunotherapy is a strategy that is moving to the frontier of cancer treatment in the current decade. In this study, we show evidence that 3-(2-nitrophenyl) propionic acid-paclitaxel nanoparticles (NPPA-PTX NPs), act as immunogenic cell death (ICD) inducers, stimulating an antitumor response which results in synergistic antitumor activity by combining anti-PD-L1 antibody (aPD-L1) . To investigate the antitumor immunity induced by NPPA-PTX NPs, the expression of both ICD marker calreticulin (CRT) and high mobility group box 1 (HMGB1) were analyzed. In addition, the antitumor activity of NPPA-PTX NPs combined with aPD-L1 was also investigated. The immune response was also measured through quantitation of the infiltration of T cells and the secretion of pro-inflammatory cytokines. The results demonstrate that NPPA-PTX NPs induce ICD of MDA-MB-231 and 4T1 cells through upregulation of CRT and HMGB1, reactivating the antitumor immunity via recruitment of infiltrating CD3+, CD4+, CD8+ T cells, secreting IFN-γ, TNF-α, and the enhanced antitumor activity by combining with aPD-L1. These data suggest that the combined therapy has a synergistic antitumor activity and has the potential to be developed into a novel therapeutic regimen for cancer patients.
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http://dx.doi.org/10.1080/10717544.2021.1909180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079060PMC
December 2021

Ecological Risk from Toxic Metals in Sediments of the Yangtze, Yellow, Pearl, and Liaohe Rivers, China.

Bull Environ Contam Toxicol 2021 Apr 16. Epub 2021 Apr 16.

College of Resources and Environment, Hunan Agricultural University, Changsha, 410128, China.

In this study, the concentrations of six toxic metals (Cd, Cr, Cu, Ni, Pb, and Zn) in surface sediments within the Yangtze, Yellow, Pearl, and Liaohe rivers, China, were analyzed, and their associated pollution statuses and potential ecological risks were assessed using the geoaccumulation index (I), sediment quality guidelines (SQGs), and the potential ecological risk index (RI). Relatively high toxic metal concentrations were observed in the Pearl and Yangtze rivers, whereas relatively low concentrations were observed in the Yellow and Liaohe rivers. In the Yangtze, Pearl, and Liaohe rivers, the concentrations of these six toxic metals were higher than their background values. Based on the SQGs, the concentrations of Cd, Cr, and Cu in the four rivers were found to be higher than the threshold effect levels (TELs) but lower than the probable effect levels (PELs); however, the concentration of Ni exceeded the PEL in the Pearl River sediments. The I index indicated that all four rivers were heavily contaminated with Cd. The RI of the Pearl and Yellow rivers was classed as high and low, respectively, and that of the Yangtze and Liaohe rivers as moderate. The pollution status of the sediments in the four major rivers was explored in relation to the geochemical background, the ecological toxicity of metals, and the sensitivity of the local benthic communities. These results provide meaningful information for directing river management priorities.
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http://dx.doi.org/10.1007/s00128-021-03229-0DOI Listing
April 2021

Enhanced tumour penetration and prolonged circulation in blood of polyzwitterion-drug conjugates with cell-membrane affinity.

Nat Biomed Eng 2021 Apr 15. Epub 2021 Apr 15.

Zhejiang Key Laboratory of Smart BioMaterials and Center for Bionanoengineering, College of Chemical and Biological Engineering, Zhejiang University, Hangzhou, China.

Effective anticancer nanomedicines need to exhibit prolonged circulation in blood, to extravasate and accumulate in tumours, and to be taken up by tumour cells. These contrasting criteria for persistent circulation and cell-membrane affinity have often led to complex nanoparticle designs with hampered clinical translatability. Here, we show that conjugates of small-molecule anticancer drugs with the polyzwitterion poly(2-(N-oxide-N,N-diethylamino)ethyl methacrylate) have long blood-circulation half-lives and bind reversibly to cell membranes, owing to the negligible interaction of the polyzwitterion with proteins and its weak interaction with phospholipids. Adsorption of the polyzwitterion-drug conjugates to tumour endothelial cells and then to cancer cells favoured their transcytosis-mediated extravasation into tumour interstitium and infiltration into tumours, and led to the eradication of large tumours and patient-derived tumour xenografts in mice. The simplicity and potency of the polyzwitterion-drug conjugates should facilitate the design of translational anticancer nanomedicines.
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http://dx.doi.org/10.1038/s41551-021-00701-4DOI Listing
April 2021

Myeloid Cell-associated Resistance to PD-1/PD-L1 Blockade in Urothelial Cancer Revealed Through Bulk and Single-cell RNA Sequencing.

Clin Cancer Res 2021 Apr 9. Epub 2021 Apr 9.

Division of Hematology Oncology, Department of Medicine, Icahn School of Medicine at Mount Sinai, Tisch Cancer Institute, New York, New York.

Purpose: To define dominant molecular and cellular features associated with PD-1/PD-L1 blockade resistance in metastatic urothelial cancer.

Experimental Design: We pursued an unbiased approach using bulk RNA sequencing data from two clinical trials to discover (IMvigor 210) and validate (CheckMate 275) pretreatment molecular features associated with resistance to PD-1/PD-L1 blockade in metastatic urothelial cancer. We then generated single-cell RNA sequencing (scRNA-seq) data from muscle-invasive bladder cancer specimens to dissect the cellular composition underlying the identified gene signatures.

Results: We identified an adaptive immune response gene signature associated with response and a protumorigenic inflammation gene signature associated with resistance to PD-1/PD-L1 blockade. The adaptive immune response:protumorigenic inflammation signature expression ratio, coined the 2IR score, best correlated with clinical outcomes, and was externally validated. Mapping these bulk gene signatures onto scRNA-seq data uncovered their underlying cellular diversity, with prominent expression of the protumorigenic inflammation signature by myeloid phagocytic cells. However, heterogeneity in expression of adaptive immune and protumorigenic inflammation genes was observed among single myeloid phagocytic cells, quantified as the myeloid single cell immune:protumorigenic inflammation ratio (M2IR) score. Single myeloid phagocytic cells with low M2IR scores demonstrated upregulation of proinflammatory cytokines/chemokines and downregulation of antigen presentation genes, were unrelated to M1 versus M2 polarization, and were enriched in pretreatment blood samples from patients with PD-L1 blockade-resistant metastatic urothelial cancer.

Conclusions: The balance of adaptive immunity and protumorigenic inflammation in individual tumor microenvironments is associated with PD-1/PD-L1 resistance in urothelial cancer with the latter linked to a proinflammatory cellular state of myeloid phagocytic cells detectable in tumor and blood.
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http://dx.doi.org/10.1158/1078-0432.CCR-20-4574DOI Listing
April 2021

Oral Probiotic Vaccine Expressing Koi Herpesvirus (KHV) ORF81 Protein Delivered by Chitosan-Alginate Capsules Is a Promising Strategy for Mass Oral Vaccination of Carps against KHV Infection.

J Virol 2021 05 24;95(12). Epub 2021 May 24.

Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Northeast Agricultural University, Harbin, People's Republic of China

Koi herpesvirus (KHV) is highly contagious and lethal to cyprinid fish, causing significant economic losses to the carp aquaculture industry, particularly to koi carp breeders. Vaccines delivered through intramuscular needle injection or gene gun are not suitable for mass vaccination of carp. So, the development of cost-effective oral vaccines that are easily applicable at a farm level is highly desirable. In this study, we utilized chitosan-alginate capsules as an oral delivery system for a live probiotic () vaccine, pYG-KHV-ORF81/LR CIQ249, expressing KHV ORF81 protein. The tolerance of the encapsulated recombinant to various digestive environments and the ability of the probiotic strain to colonize the intestine of carp was tested. The immunogenicity and the protective efficacy of the encapsulated probiotic vaccine was evaluated by determining IgM levels, lymphocyte proliferation, expression of immune-related genes, and viral challenge to vaccinated fish. It was clear that the chitosan-alginate capsules protected the probiotic vaccine effectively against extreme digestive environments, and a significant level ( < 0.01) of antigen-specific IgM with KHV-neutralizing activity was detected, which provided a protection rate of ca. 85% for koi carp against KHV challenge. The strategy of using chitosan-alginate capsules to deliver probiotic vaccines is easily applicable for mass oral vaccination of fish. An oral probiotic vaccine, pYG-KHV-ORF81/LR CIQ249, encapsulated by chitosan-alginate capsules as an oral delivery system was developed for koi carp against koi herpesvirus (KHV) infection. This encapsulated probiotic vaccine can be protected from various digestive environments and maintain effectively high viability, showing a good tolerance to digestive environments. This encapsulated probiotic vaccine has a good immunogenicity in koi carp via oral vaccination, and a significant level of antigen-specific IgM was effectively induced after oral vaccination, displaying effective KHV-neutralizing activity. This encapsulated probiotic vaccine can provide effective protection for koi carp against KHV challenge, which is handling-stress free for the fish, cost effective, and suitable for the mass oral vaccination of koi carp at a farm level, suggesting a promising vaccine strategy for fish.
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http://dx.doi.org/10.1128/JVI.00415-21DOI Listing
May 2021

Effects of transjugular intrahepatic portosystemic shunt using the Viatorr stent on hepatic reserve function in patients with cirrhosis.

World J Clin Cases 2021 Mar;9(7):1532-1542

Department of Gastroenterology, General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China.

Background: As transjugular intrahepatic portosystemic shunt (TIPS) creation alters the hemodynamic status of the portal system, whether reduced portal blood supply affects the synthetic reserve function of the liver has been the focus of clinical attention. Since the Viatorr stent entered the Chinese market in 2015, it has not yet been widely used in clinical practice. Further, unlike other countries, the main cause of liver cirrhosis in China is viral hepatitis. Therefore, use of the Viatorr stent to establish a TIPS channel in patients with liver cirrhosis with differing etiologies is of great clinical interest.

Aim: To investigate factors affecting changes in liver reserve function after TIPS Viatorr stent implantation.

Methods: Clinical data from 200 patients with cirrhotic portal hypertension who received TIPS treatment from March 2016 to March 2020 were analyzed retrospectively. The patients were divided into three groups (A-C), according to their disease etiology, with post-hepatitis, autoimmune, and alcoholic cirrhosis, respectively. Preoperative and postoperative liver and renal function and coagulation data, Child-Pugh grade, and model for end-stage liver disease (MELD) scores were collected. Statistical analyses were performed using the -test or chi-square test. The incidence and of hepatic encephalopathy and patient survival were calculated using Kaplan-Meier method.

Results: The surgical success rate was 100%, with mean portal pressure gradient (mmHg) decreasing from 25.5 ± 5.22 to 10.04 ± 2.76 ( = 45.80; < 0.001). After 24 mo, the cumulative incidence of hepatic encephalopathy in group A was significantly lower than that in group B/C, while the cumulative survival rate was significantly higher in group A than in group B/C ( < 0.05 for both). The Child-Pugh score for group A was 6.96 ± 1.21, which was significantly better than those of groups B (7.42 ± 0.99; = -2.44; = 0.016) and C (7.52 ± 1.12; = -2.67; = 0.009). Further, the MELD score for group A (9.62 ± 2.19) was significantly better than those for groups B (10.64 ± 1.90; = -2.92; = 0.004) and C (10.82 ± 2.01; = -3.29; = 0.001).

Conclusion: Insertion of 8 mm internal diameter Viatorr stent has no significant effects on liver reserve function. Changes of liver reserve function in the medium and long term may be related to the etiology and treatment of portal hypertension.
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http://dx.doi.org/10.12998/wjcc.v9.i7.1532DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7942045PMC
March 2021

Structural Mechanism of Cooperative Regulation of Calcium-Sensing Receptor-Mediated Cellular Signaling.

Curr Opin Physiol 2020 Oct 11;17:269-277. Epub 2020 Sep 11.

Department of Chemistry, Center for Diagnostics and Therapeutics and Advanced Translational Imaging Facility, Georgia State University, Atlanta, GA, 30303.

Calcaium sensing receptors (CaSRs) play a central role in regulating extracellular calcium (Ca) homeostasis and many (patho)physiological processes. This regulation is primarily orchestrated in response to extracellular stimuli via the extracellular domain (ECD). This paper first reviews the modeled structure of the CaSR ECD and the prediction and investigation of the Ca and amino acid binding sites. Several recently solved X-ray structures are then compared to support a proposed CaSR activation model involving functional cooperativity. The review also discusses recent implications for drug development. These studies provide new insights into the molecular basis of diseases and the design of therapeutic agents that target CaSR and other family C G protein-coupled receptors (cGPCRs).
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http://dx.doi.org/10.1016/j.cophys.2020.08.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7943033PMC
October 2020

Tocilizumab in patients with moderate or severe COVID-19: a randomized, controlled, open-label, multicenter trial.

Front Med 2021 Mar 9. Epub 2021 Mar 9.

Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital), Hefei, 230001, China.

Tocilizumab has been reported to attenuate the "cytokine storm" in COVID-19 patients. We attempted to verify the effectiveness and safety of tocilizumab therapy in COVID-19 and identify patients most likely to benefit from this treatment. We conducted a randomized, controlled, open-label multicenter trial among COVID-19 patients. The patients were randomly assigned in a 1:1 ratio to receive either tocilizumab in addition to standard care or standard care alone. The cure rate, changes of oxygen saturation and interference, and inflammation biomarkers were observed. Thirty-three patients were randomized to the tocilizumab group, and 32 patients to the control group. The cure rate in the tocilizumab group was higher than that in the control group, but the difference was not statistically significant (94.12% vs. 87.10%, rate difference 95% CI-7.19%-21.23%, P = 0.4133). The improvement in hypoxia for the tocilizumab group was higher from day 4 onward and statistically significant from day 12 (P = 0.0359). In moderate disease patients with bilateral pulmonary lesions, the hypoxia ameliorated earlier after tocilizumab treatment, and less patients (1/12, 8.33%) needed an increase of inhaled oxygen concentration compared with the controls (4/6, 66.67%; rate difference 95% CI-99.17% to-17.50%, P = 0.0217). No severe adverse events occurred. More mild temporary adverse events were recorded in tocilizumab recipients (20/34, 58.82%) than the controls (4/31, 12.90%). Tocilizumab can improve hypoxia without unacceptable side effect profile and significant influences on the time virus load becomes negative. For patients with bilateral pulmonary lesions and elevated IL-6 levels, tocilizumab could be recommended to improve outcome.
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http://dx.doi.org/10.1007/s11684-020-0824-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7940448PMC
March 2021

[Effective medicinal ingredients and screening of excellent germplasm in Rubus chingii].

Zhongguo Zhong Yao Za Zhi 2021 Feb;46(3):575-581

State Key Laboratory of Subtropical Silviculture, Zhejiang A&F University Hangzhou 311300, China.

In order to provide rationale for selection of good germplasm in Rubus chingii, main effective medicinal ingredients of green fruit such as gallic acid, ellagic acid, kaempferol-3-rutinoside, astragalin and tiliroside were measured using UPLC for the samples collected from Chun'an county of Zhejiang province, and such parameters as soluble solid contents of ripe fruit of some samples were also measured to study variation among individuals and correlation. It has been found that there were differences among individuals in the contents of gallic acid, ellagic acid, kaempferol-3-rutinoside, astragalin and tiliroside, which ranged from 0.010 2%-0.027 4%, 0.089 5%-0.291 1%, 0.010 5%-0.114 8%, 0.005 8%-0.041 2% and 0.010 9%-0.086 3%, respectively, with a CV of 18.60%, 27.02%, 44.23%, 44.17% and 47.29%, respectively. Gallic acid was positively correlated with ellagic acid, but negatively with kaempferol-3-rutinoside and astragalin significantly. Significantly positive correlation existed between kaempferol-3-rutinoside, astragalin and linden glycoside as well as between ellagic acid and fruit shape index of ripe fruit and between linden glycoside and the content of soluble solids. 51.35% of the individuals had a content of soluble solids more than 15%. Therefore, abundant variations have been found among individuals in effective medicinal ingredients in R. chingii, which shows great potential for selection, but only do 7.61% of the individuals meet the requirement of Chinese pharmacopoeia in terms of the contents of effective medicinal ingredients. Therefore, selection could be first performed in terms of fruit shape index of ripe red fruit, followed by the contents of ellagic acid and kaempferol-3-rutinoside measured. The individuals, in which the contents of effective medicinal ingredients don't meet the requirement of Chinese pharmacopoeia, could be considered for the selection in terms of edible fresh fruit.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20201025.102DOI Listing
February 2021

Tension-Relaxation In Vivo Computing Principle for Tumor Sensitization and Targeting.

IEEE Trans Cybern 2021 Feb 18;PP. Epub 2021 Feb 18.

By modeling the tumor sensitization and targeting (TST) as a natural computational process, we have proposed the framework of nanorobots-assisted in vivo computation. The externally manipulable nanorobots are steered to detect the tumor in the high-risk tissue, which is analogous to the process of searching for the optimal solution by the computing agents in the search space. To overcome the constraint of a nanorobotic platform that can only generate a uniform magnetic field to actuate the nanorobots, we have proposed the weak priority evolution strategy (WP-ES) in our previous works. However, these works do not consider the proportions of the nanorobot control and tracking operations, which are part and parcel of in vivo computation as the control operation aims at searching for the tumor effectively while the tracking mode is used for gathering information about the biological gradient function (BGF). Careful planning about the durations spent in these operations is needed for optimal performance of the TST strategy. To account for this issue, in the current article, we propose a novel computational principle, called the tension-relaxation (T-R) principle, to balance the displacements of nanorobots during each control and tracking cycle. Furthermore, we build three tumor vascular models with different sizes to represent three different targeting regions as the morphology of tumor vasculature determined by the tumor growth process is an important factor affecting TST. We carry out the computational experiments for tumors with three different sizes for several representative landscapes by introducing the T-R principle into the WP-ES-based swarm intelligence algorithms and considering the realistic internal constraints. The experimental outcomes demonstrate the effectiveness of the proposed TST strategy.
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http://dx.doi.org/10.1109/TCYB.2021.3052731DOI Listing
February 2021

In situ growth of Z-scheme CuS/CuSCN heterojunction to passivate surface defects and enhance charge transport.

J Colloid Interface Sci 2021 May 2;590:407-414. Epub 2021 Feb 2.

College of Materials and Chemistry, China Jiliang University, Hangzhou 300018, Zhejiang, China.

Copper thiocyanate (CuSCN) has been considered as a promising hole transport material (HTMs), attributing to its inherent stability, low-cost, and suitable energy levels. To make it more attractive in practical applications, the drawbacks of CuSCN in poor charge transport and serious defect recombination are bottlenecks that need to be overcome. In this work, we propose an effective strategy of in-situ decorating CuSCN with copper sulfide quantum dots (CuS QDs), a simple one-step electrochemical deposition process, to solve these issues. Compared with the pristine CuSCN, the constructed Z-Scheme heterojunction of CuS QDs/CuSCN can significantly promote charge transport and restrict recombination. In addition, the decorated CuS QDs can not only passivate defects of CuSCN, but also provide more contacting sites to facilitate hole injection when employing as HTM. As a result, the average bulk charge lifetime was improved from 0.37 ms to 0.47 ms, and the surface recombination rate constant was suppressed. We believe that the excellent performances will pave it toward practical device applications, including solar cells, photocatalysis, photoelectrochemical sensors, and light-emitting diodes.
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http://dx.doi.org/10.1016/j.jcis.2020.12.126DOI Listing
May 2021

Gravity determines the direction of nerve roots sedimentation in the lumbar spinal canal.

BMC Musculoskelet Disord 2021 Feb 8;22(1):154. Epub 2021 Feb 8.

Operating room, Sanmen People's Hospital, Taizhou, China.

Objectives: To investigate the role of gravity in the sedimentation of lumbar spine nerve roots using magnetic resonance (MR) imaging of various body positions.

Methods: A total of 56 patients, who suffered from back pain and underwent conventional supine lumbar spine MR imaging, were selected from sanmen hospital database. All the patients were called back to our hospital to perform MR imaging in prone position or lateral position. Furthermore, the sedimentation sign (SedSign) was determined based on the suspension of the nerve roots in the dural sac on cross-sectional MR images, and 31 cases were rated as positive and another 25 cases were negative.

Results: The mean age of negative SedSign group was significantly younger than that of positive SedSign group (51.7 ± 8.7 vs 68.4 ± 10.5, P < 0.05). The constitutions of clinical diagnosis were significantly different between patients with a positive SedSign and those with a negative SedSign (P < 0.001). Overall, nerve roots of the vast majority of patients (48/56, 85.7%) subsided to the ventral side of the dural sac on the prone MR images, although that of 8 (14.3%) patients remain stay in the dorsal side of dural sac. Nerve roots of only one patient with negative SedSign did not settle to the ventral dural sac, while this phenomenon occurred in 7 patients in positive SedSign group (4% vs 22.6%, P < 0.001). In addition, the nerve roots of all the five patients subsided to the left side of dural sac on lateral position MR images.

Conclusions: The nerve roots sedimentation followed the direction of gravity. Positive SedSign may be a MR sign of lumbar pathology involved the spinal canal.
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http://dx.doi.org/10.1186/s12891-021-04032-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7871597PMC
February 2021

Amorphous Drug-Polymer Salt with High Stability under Tropical Conditions and Fast Dissolution: The Case of Clofazimine and Poly(acrylic acid).

Mol Pharm 2021 03 1;18(3):1364-1372. Epub 2021 Feb 1.

We report that the stability of amorphous clofazimine (CFZ) against crystallization is vastly improved by salt formation with a polymer without sacrificing dissolution rate. A simple slurry method was used to produce the amorphous salt of CFZ with poly(acrylic acid) (PAA) at 75 wt % drug loading. The synthesis was performed under a mild condition suitable for thermally unstable drugs and polymers. Salt formation was confirmed by visible spectroscopy and glass temperature elevation. The amorphous salt at 75 wt % drug loading is remarkably stable against crystallization at 40 °C and 75% RH for at least 180 days. In contrast, the amorphous solid dispersion containing the un-ionized CFZ dispersed in poly(vinylpyrrolidone) crystallized in 1 week under the same condition. The high stability of the amorphous drug-polymer salt is a result of the absence of a drug-polymer crystalline structure, reduced driving force for crystallizing the free base, and reduced molecular mobility. Despite the elevated stability, the amorphous drug-polymer salt showed fast dissolution and high solution concentration in two biorelevant media (SGF and FaSSIF). Additionally, the amorphous CFZ-PAA salt has improved tabletability and powder flow relative to crystalline CFZ. The CFZ-PAA example suggests a general method to prepare amorphous drugs with high physical stability under tropical conditions and fast dissolution.
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http://dx.doi.org/10.1021/acs.molpharmaceut.0c01180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7927142PMC
March 2021

Characterization of Formononetin Sulfonation in SULT1A3 Overexpressing HKE293 Cells: Involvement of Multidrug Resistance-Associated Protein 4 in Excretion of Sulfate.

Front Pharmacol 2020 11;11:614756. Epub 2021 Jan 11.

Institute for Innovative Drug Design and Evaluation, School of Pharmacy, Henan University, Kaifeng, China.

Formononetin is one of the main active compounds of traditional Chinese herbal medicine . However, disposition of formononetin via sulfonation pathway remains undefined. Here, expression-activity correlation was performed to identify the contributing of SULT1A3 to formononetin metabolism. Then the sulfonation of formononetin and excretion of its sulfate were investigated in SULT1A3 overexpressing human embryonic kidney 293 cells (or HKE-SULT1A3 cells) with significant expression of breast cancer resistance protein (BCRP) and multidrug resistance-associated protein 4 (MRP4). As a result, formononetin sulfonation was significantly correlated with SULT1A3 protein levels (r = 0.728; < 0.05) in a bank of individual human intestine S9 fractions (n = 9). HEK-SULT1A3 cells catalyzed formononetin formation of a monosulfate metabolite. Sulfate formation of formononetin in HEK-SULT1A3 cell lysate followed the Michaelis-Menten kinetics (V = 13.94 pmol/min/mg and K = 6.17 μM). Reduced activity of MRP4 by MK-571 caused significant decrease in the excretion rate (79.1%-94.6%) and efflux clearance (85.3%-98.0%) of formononetin sulfate, whereas the BCRP specific inhibitor Ko143 had no effect. Furthermore, silencing of MRP4 led to obvious decrease in sulfate excretion rates (>32.8%) and efflux clearance (>50.6%). It was worth noting that the fraction of dose metabolized (f), an indicator of the extent of drug sulfonation, was also decreased (maximal 26.7%) with the knockdown of MRP4. In conclusion, SULT1A3 was of great significance in determining sulfonation of formononetin. HEK-SULT1A3 cells catalyzed formononetin formation of a monosulfate. MRP4 mainly contributed to cellular excretion of formononetin sulfate and further mediated the intracellular sulfonation of formononetin.
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http://dx.doi.org/10.3389/fphar.2020.614756DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836013PMC
January 2021

A survey of jaagsiekte sheep retrovirus (JSRV) infection in sheep in the three northeastern provinces of China.

Arch Virol 2021 Mar 24;166(3):831-840. Epub 2021 Jan 24.

Heilongjiang Key Laboratory for Animal Disease Control and Pharmaceutical Development, Northeast Agricultural University, Harbin, People's Republic of China.

Ovine pulmonary adenomatosis (OPA) is caused by jaagsiekte sheep retrovirus (JSRV) and is a chronic, progressive, and infectious neoplastic lung disease in sheep, which causes significant economic losses to the sheep industry. Neither a vaccine nor serological diagnostic methods to detect OPA are available. We performed a JSRV infection survey in sheep using blood samples (n = 1,372) collected in the three northeastern provinces of China (i.e., Inner Mongolia, Heilongjiang, and Jilin) to determine JSRV infection status in sheep herds using a real-time PCR assay targeting the gag gene of JSRV. The ovine endogenous retrovirus sequence was successfully amplified in all sheep samples tested (296 from the Inner Mongolia Autonomous Region, 255 from Jilin province, and 821 from Heilongjiang province). Subsequently, we attempted to distinguish exogenous JSRV (exJSRV) and endogenous JSRV (enJSRV) infections in these JSRV-positive samples using a combination assay that identifies a ScaI restriction site in an amplified 229-bp fragment of the gag gene of JSRV and a "LHMKYXXM" motif in the cytoplasmic tail region of the JSRV envelope protein. The ScaI restriction site is present in all known oncogenic JSRVs but absent in ovine endogenous retroviruses, while the "LHMKYXXM" motif is in all known exJSRVs but not in enJSRVs. Interestingly, one JSRV strain (HH13) from Heilongjiang province contained the "LHMKYXXM" motif but not the ScaI enzyme site. Phylogenetic analysis showed that strain HH13 was closely related to strain enJSRV-21 reported in the USA, indicating that HH13 could be an exogenous virus. Our results provide valuable information for further research on the genetic evolution and pathogenesis of JSRV.
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http://dx.doi.org/10.1007/s00705-020-04919-6DOI Listing
March 2021

Isolation, identification, and phylogenetic analysis of subgroup III strain of bovine respiratory syncytial virus contributed to outbreak of acute respiratory disease among cattle in Northeast China.

Virulence 2021 12;12(1):404-414

Heilongjiang Province Key Laboratory for Animal Disease Control and Pharmaceutical Development, Northeast Agricultural University , Harbin, China.

Bovine respiratory syncytial virus (BRSV) is a clinically important causative agent of acute respiratory diseases in postweaning calves and feedlot cattle and causes numerous economic losses to the cattle industry. In June 2018, an outbreak of an acute respiratory disease occurred among 4- to 10-month-old calves on three intensive beef cattle farms in Heilongjiang Province, Northeast China, with a 27.42% morbidity rate (329/1200) and a > 25% mortality rate (85/329). Using next-generation sequencing, we comprehensively analyzed microbial diversity in the lung samples of the diseased cattle and found that the causative agent of this epidemic outbreak is mainly a bovine orthopneumovirus named BRSV strain DQ. We then isolated and confirmed the virus by RT-PCR and an indirect immunofluorescence assay. Phylogenetic analysis of genes , and of BRSV strain DQ showed that this strain shares the highest genetic similarity with strains USII/S1, 15489, V41, and NY487834 belonging to subgroup III of BRSV. This is the first report of subgroup III strain of BRSV presence in China. Heilongjiang Province is a major cattle-breeding province in China; therefore, it is necessary to test for BRSV in the cattle trade and to conduct region-extended epidemiological surveillance for BRSV in China.
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http://dx.doi.org/10.1080/21505594.2021.1872178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834082PMC
December 2021

Meta-analysis of Efficacy and Safety of Inhaled Ciprofloxacin in Non-cystic Fibrosis Bronchiectasis Patients.

Intern Med J 2021 Jan 19. Epub 2021 Jan 19.

Department of Respiratory and Critical Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, China.

Background: No antibiotic therapies have been approved for reducing exacerbations and preventing disease progression in non-cystic fibrosis bronchiectasis (NCFB) patients. Several recent clinical studies have investigated the feasibility of inhaled ciprofloxacin in NCFB, whereas the results were controversial.

Method: Electrical databases Medline and Cochrane library were retrieved from inception through December, 2019. Randomized controlled trials (RCTs) comparing inhaled ciprofloxacin and placebo were selected. The primary outcomes were time to first exacerbation, frequency of exacerbations and the change in sputum Pseudomonas aeruginosa density.

Results: A total of five articles involving 6 RCTs were finally included in the analysis. The time to first exacerbation was significantly prolonged by inhaled ciprofloxacin (Hazard ratio: 0.72, 95% confidence interval (CI): 0.63-0.82), with low heterogeneity (I = 23%). Inhalation of ciprofloxacin significantly reduced frequency of exacerbations (Risk ratio: 0.70, 95% CI: 0.61-0.79) and decreased density of sputum Pseudomonas aeruginosa (Weighted mean difference: -2.11 log CFU/g, 95% CI: -2.96 to -1.27 log CFU/g) compared with placebo. No significant between-group differences in mortality, adverse events and discontinuation rate were observed. Further indirect treatment comparison showed no differences between the two types of inhaled ciprofloxacin in all outcomes of interest.

Conclusion: Ciprofloxacin inhalation treatment significantly prolonged the time to first exacerbation, reduced the frequency of exacerbations and decreased sputum Pseudomonas aeruginosa density, and was well-tolerated. Ciprofloxacin inhalation is promising in treatment of NCFB. This article is protected by copyright. All rights reserved.
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http://dx.doi.org/10.1111/imj.15210DOI Listing
January 2021

The "Traditional Chinese medicine regulating liver regeneration" treatment plan for reducing mortality of patients with hepatitis B-related liver failure based on real-world clinical data.

Front Med 2021 Jan 12. Epub 2021 Jan 12.

Institute of Liver Diseases, Hubei Provincial Hospital of Traditional Chinese Medicine, Wuhan, 430061, China.

On the basis of real-world clinical data, the study aimed to explore the effect and mechanisms of the treatment plan of "traditional Chinese medicine (TCM) regulating liver regeneration." A total of 457 patients with HBV-related liver failure were retrospectively collected. The patients were divided into three groups: the modern medicine control group (MMC group), patients treated with routine medical treatment; the control group combining traditional Chinese and Western medicine (CTW), patients treated with routine medical treatment plus the common TCM formula; and the treatment group of "TCM regulating liver regeneration" (RLR), patients treated with both routine medical treatment and the special TCM formula of RLR. After 8 weeks of treatment, the mortality of patients in the RLR group (12.31%) was significantly lower than those in the MMC (50%) and CTW (29.11%) groups. Total bilirubin level significantly decreased and albumin increased in the RLR group when compared with the MMC and CTW groups (P < 0.05). In addition, there were significant differences in the expression of several cytokines related to liver regeneration in the RLR group compared with the MMC group. RLR treatment can decrease jaundice, improve liver function, and significantly reduce the mortality in patients with HBV-related liver failure. The mechanism may be related to the role of RLR treatment in influencing cytokines related to liver regeneration.
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http://dx.doi.org/10.1007/s11684-020-0790-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7801774PMC
January 2021

Epithelial expression and role of secreted STC1 on asthma airway hyperresponsiveness through calcium channel modulation.

Allergy 2020 Dec 30. Epub 2020 Dec 30.

Department of Respiratory & Critical Care Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Background: Asthma is characterized by airway hyperresponsiveness (AHR), inflammation, and airway remodeling. Airway hyperresponsiveness results from enhanced airway smooth muscle (ASM) contraction potentially under the control of an epithelium-derived relaxing factor (EpDRF). However, relatively rare is known about EpDRF. We aimed to elucidate the role of epithelium-derived stanniocalcin-1 (STC1) on AHR and ASM contraction.

Methods: Stanniocalcin-1 levels in the serum of asthmatic patients and healthy volunteers and in bronchoalveolar lavage fluid (BALF) from ovalbumin (OVA)-challenged mice were measured by ELISA. The effects of exogenous STC1 on AHR and on inflammation were examined in mice. IL-13 modulation of STC1 mRNA and protein levels was studied in human bronchial epithelial cell lines (16HBE). The function of STC1 on Ca influx and ASM contraction was examined ex vivo.

Results: Serum STC1 was decreased in asthma (n = 93) compared with healthy volunteers (1071 ± 30.4 vs 1414 ± 75.1 pg/ml, p < 0.0001, n = 23) and correlated with asthma control (p = 0.0270), lung function (FEV1, p = 0.0130), and serum IL-13 levels (p = 0.0009). Treatment of ten asthmatic subjects with inhaled corticosteroids/long-acting beta2-agonists (ICS/LABA) for 1 year enhanced STC1 expression which correlated with improved asthma control (p = 0.022). STC1 was mainly expressed in bronchial epithelium and intranasal administration of recombinant human STC1 (rhSTC1) reduced AHR and inflammation in mice. IL-13 suppressed STC1 release from 16HBE, whereas rhSTC1 blocked store-operated Ca entry (SOCE) by suppressing stromal interaction molecule 1 (STIM1) and further inhibited ASM cell contractility by suppressing Ca -dependent myosin light chain (MLC) phosphorylation.

Conclusion: Our data indicate that STC1 deficiency in asthmatic airways promotes STIM1 hyperactivity, enhanced ASM contraction, and AHR. STC1 may be a candidate EpDRF.
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http://dx.doi.org/10.1111/all.14727DOI Listing
December 2020

[Post-marketing intensive safety monitoring of Injection of Xuesaitong (lyophilized) in 30097 cases].

Zhongguo Zhong Yao Za Zhi 2020 Oct;45(20):5029-5033

Evidence-based Medicine Center, Tianjin University of Traditional Chinese Medicine Tianjin 301617, China.

To investigate the safety of Injection of Xuesaitong(lyophilized) in clinical "real world" application, including the types, incidence, as well as the severity and treatment measures of adverse reactions/adverse events. This will serve as a basis for hospitals and enterprises to develop risk control measures. A prospective, multi-center, and large-sample hospital centralized monitoring method was used to conduct post-marketing safety monitoring of Injection of Xuesaitong(lyophilized) in medical institutions nationwide. Paper case report forms were adopted to collect general information, medication and adverse reaction information of patients using Injection of Xuesaitong(lyophilized). Data analysis was performed by using SAS 9.1 software. The study included 79 hospitals with 30 097 patients. 199 cases of adverse events were found in patients administered with Injection of Xuesaitong(lyophilized), a total of 206 times. Among 199 cases, 40 of them showed adverse reactions, accounting for an overall incidence of 0.13% and 95%CI[0.09%,0.17%], which was an occasional grade. There were 38 cases of mild adverse reactions, accounting for 95.0%, 2 cases of moderate adverse reactions, accounting for 5.0%. Adverse reaction symptoms were relieved in six patients, accounting for 15.0% of the total number of adverse reactions, adverse reaction symptoms disappeared in 34 cases, with an overall percentage of 85.0%. The results of the study showed the adverse reactions in patients using Injection of Xuesaitong(lyophilized) were rare and mild, with a good prognosis. Therefore, clinical administration of Injection of Xuesaitong(lyophilized) is relatively safe.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200302.503DOI Listing
October 2020

[Analysis of Injection of Xuesaitong (lyophilized) in 30097 cases in real world].

Zhongguo Zhong Yao Za Zhi 2020 Oct;45(20):5024-5028

Evidence-based Medicine Center, Tianjin University of Traditional Chinese Medicine Tianjin 301617, China.

To investigate the extensive application of Injection of Xuesaitong(lyophilized) in clinical real world study, and provide basis for clinical guidance on rational drug use and improvement of drug instructions. A prospective, multi-center, large-sample hospital centralized monitoring method was adopted to collect the general information and medication information of all patients who received Injection of Xuesaitong(lyophilized) during the study period in the respective monitoring units. Data analysis was performed using SAS 9.1 software. This study included 79 hospitals, with 30 097 patients being recruited. The patients who met the indications for stroke and hemiplegia accounted for 31.18%, those who experienced indications of chest pain and heartache accounted for 23.15%, and patients with central retinal vein occlusion indication accounted for 0.53%. The minimum single dose of Injection of Xuesaitong(lyophilized) was 20 mg, the maximum single dose was 1 000 mg, and the average single dose was(383.31±78.10) mg. 69.96% of the patients used 0.9% sodium chloride as the menstruum, 28.78% of the patients used 5% glucose as the menstruum, and 0.19% of the patients used 10% glucose as the menstruum. The minimum time for Injection of Xuesaitong(lyophilized) to dissolve is 0 min, 120 min maximally, and(14.26±13.73) min on an average basis. Patients using Injection of Xuesaitong(lyophilized) by intravenous drip accounted for 99.93%, with a slowest drip rate of 10 drops per min, fastest drip rate of 80 drops per min, and an average of(43.91±10.77) drops per min. Injection of Xuesaitong(lyophilized) was used for a minimum of 1 day and a maximum of 80 days, with an average of(8.22±5.12) days. Combined use with other injections accounted for 80.67%, 47.14% of them flushed the tube and 3.31% of them replaced infusion sets. The study found 40 cases of adverse reactions in patients with Injection of Xuesaitong(lyophilized), with an overall incidence of 0.13%(0.09% to 0.17%) for adverse reactions. In the real world application, the usage of Injection of Xuesaitong(lyophilized) basically meets the requirement of drug instructions in terms of indications, dosages, and methods of administration. However, it still needs to be improved in standardizing the selection of the menstruum, drip rate, course of treatment, and the combined usage of medicine.
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http://dx.doi.org/10.19540/j.cnki.cjcmm.20200611.501DOI Listing
October 2020

PKM2-Induced the Phosphorylation of Histone H3 Contributes to EGF-Mediated PD-L1 Transcription in HCC.

Front Pharmacol 2020 26;11:577108. Epub 2020 Nov 26.

Institute for Innovative Drug Design and Evaluation, School of Pharmacy, Henan University, Kaifeng, China.

High expression of programmed death-ligand-1 (PD-L1) in hepatocellular carcinoma (HCC) cells usually inhibits the proliferation and functions of T cells, leading to immune suppression in tumor microenvironment. However, very little has been described regarding the mechanism of PD-L1 overexpression in HCC cells. In the present study, we found epidermal growth factor (EGF) stimulation promoted the expression of PD-L1 mRNA and protein in HCC cells. Inhibition of epidermal growth factor receptor (EGFR) could reverse EGF-induced the expression of PD-L1 mRNA and protein. Subsequently, we also observed that the phosphorylation level of Pyruvate kinase isoform M2 (PKM2) at Ser site was also increased in response to EGF stimulation. Expression of a phosphorylation-mimic PKM2 S37D mutant stimulated PD-L1 expression as well as H3-Thr phosphorylation in HCC cells, while inhibition of PKM2 significantly blocked EGF-induced PD-L1 expression and H3-Thr phosphorylation. Furthermore, mutation of Thr of histone H3 into alanine abrogated EGF-induced mRNA and protein expression of PD-L1, Chromatin immunoprecipitation (ChIP) assay also suggested that EGF treatment resulted in enhanced H3-Thr phosphorylation at the PD-L1 promoter. In a diethylnitrosamine (DEN)-induced rat model of HCC, we found that the expression of phosphorylated EGFR, PKM2 nuclear expression, H3-Thr phosphorylation as well as PD-L1 mRNA and protein was higher in the livers than that in normal rat livers. Taken together, our study suggested that PKM2-dependent histone H3-Thr phosphorylation was crucial for EGF-induced PD-L1 expression at transcriptional level in HCC. These findings may provide an alternative target for the treatment of hepatocellular carcinoma.
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http://dx.doi.org/10.3389/fphar.2020.577108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7725877PMC
November 2020