Publications by authors named "Hongwei Wang"

772 Publications

Inhibition of HSP90 reverses STAT3-mediated muscle wasting in cancer cachexia mice.

Br J Pharmacol 2021 Jul 15. Epub 2021 Jul 15.

Center for Translational Medicine and Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing, P.R. China.

Background And Purpose: Cancer cachexia is one of the most common causes of death among cancer patients; no effective anti-cachectic treatment is currently available. In experimental cachectic animal models, aberrant activation of STAT3 in skeletal muscle has been found to contribute to muscle wasting. However, its clinical association, the factors regulating STAT3 activation, and the molecular mechanisms remain incompletely understood.

Experimental Approach: The expression of HSP90 and the activation of STAT3 were detected in muscle from the patients with cancer cachexia or the tumour-bearing cachectic mice. HSP90 inhibitors, including 17DMAG and PU-H71, were administered to cachexic mice, and cachexia parameters, such as weight loss, food intake, survival rate, body composition, serum metabolites, muscle wasting pathology, and catabolic activation, were measured and analyzed. The in vitro coculture of C2C12 myotube cells with C26 conditioned media (CM) was performed to address the pathological mechanism of catabolic muscle wasting. The roles of HSP90, STAT3, and FOXO1 in myotube atrophy were explored via overexpression or knockdown.

Results: Here, we show that an enhanced interaction between activated STAT3 and HSP90, which were observed in the skeletal muscle of cancer cachexia patients, is a crucial event for the development of cachectic muscle wasting. Administration of HSP90 inhibitors 17DMAG and PU-H71 alleviated the muscle wasting in C26 and LLC tumor-bearing cachectic mice models or the myotube atrophy of C2C12 cells induced by C26 conditional medium. Prolonged STAT3 activation transactivated FOXO1 by binding directly to its promoter and triggered the muscle wasting in a FOXO1-dependent manner in muscle cells.

Conclusion And Implications: Our results demonstrate that the HSP90/STAT3/FOXO1 axis plays a critical role in cachectic muscle wasting, which might serve as a potential therapeutic target for the treatment of cancer cachexia.
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http://dx.doi.org/10.1111/bph.15625DOI Listing
July 2021

An Integrated Approach for Discovering Noncanonical MHC-I Peptides Encoded by Small Open Reading Frames.

J Am Soc Mass Spectrom 2021 Jul 14. Epub 2021 Jul 14.

State Key Laboratory of Chemical Biology and Drug Discovery, Department of Applied Biology and Chemical Technology, Hong Kong Polytechnic University, Hong Kong SAR 999077, China.

MHC-I peptides are a group of important immunopeptides presented by major histocompatibility complex (MHC) on the cell surface for immune recognition. The majority of reported MHC-I peptides are derived from protein coding sequences, and noncanonical peptides translated from small open reading frames (sORF) are largely unknown due to the lack of accurate and sensitive detection methods. Herein we report an efficient approach that implements complementary bioinformatic strategies to improve the identification of noncanonical MHC-I peptides. In a database search strategy, noncanonical immunopeptides mapping was optimized by combining three complementary pipelines to construct predicted sORF databases from Ribo-seq data. In a peptide sequencing strategy, MS data search results were filtered against sORF databases to pin down additional noncanonical immunopeptides. In total, 308 noncanonical immunopeptides were identified from two tumor cell lines with selected ones vigorously validated. Our approach is a handy solution to identify noncanonical MHC peptides with Ribo-seq and MS data. Meanwhile, the novel noncanonical immunopeptides identified with this method could shed insights on fundamental immunology as well as cancer immunotherapies.
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http://dx.doi.org/10.1021/jasms.1c00076DOI Listing
July 2021

Proteomics provides individualized options of precision medicine for patients with gastric cancer.

Sci China Life Sci 2021 Jul 9. Epub 2021 Jul 9.

State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Department of Digestive Surgery, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, 710032, China.

While precision medicine driven by genome sequencing has revolutionized cancer care, such as lung cancer, its impact on gastric cancer (GC) has been minimal. GC patients are routinely treated with chemotherapy, but only a fraction of them receive the clinical benefit. There is an urgent need to develop biomarkers or algorithms to select chemo-sensitive patients or apply targeted therapy. Here, we carried out retrospective analyses of 1,020 formalin-fixed, paraffin-embedded GC surgical resection samples from 5 hospitals and developed a mass spectrometry-based workflow for proteomic subtyping of GC. We identified two proteomic subtypes: the chemo-sensitive group (CSG) and the chemo-insensitive group (CIG) in the discovery set. The 5-year overall survival of CSG was significantly improved in patients who had received adjuvant chemotherapy after surgery compared with those who received surgery only (64.2% vs. 49.6%; Cox P-value=0.002), whereas no such improvement was observed in CIG (50.0% vs. 58.6%; Cox P-value=0.495). We validated these results in an independent validation set. Further, differential proteome analysis uncovered 9 FDA-approved drugs that may be applicable for targeted therapy of GC. A prospective study is warranted to test these findings for future GC patient care.
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http://dx.doi.org/10.1007/s11427-021-1966-4DOI Listing
July 2021

Comparison of the Virulence in Mice and Piglets.

Front Vet Sci 2021 24;8:659244. Epub 2021 Jun 24.

The Key Lab of Veterinary Biological Products, Henan University of Science and Technology, Luoyang, China.

In this study, we compared the virulence of the most common serovars of in China, serovars 4, 5, 12, and 13 (36 strains in total) in BALB/c mice and piglets. In mice, the median lethal doses (LDs) of the four serovars were roughly 9.80 × 10-4.60 × 10 CFU, 2.10 × 10-8.85 × 10 CFU, 4.81 × 10-7.01 × 10 CFU, and 1.75 × 10-8.45 × 10 CFU, respectively. Serovar 13 showed the strongest virulence, followed by serovar 4, serovar 12, and serovar 5, but a significant difference in virulence was only observed between serovars 5 and 13. The virulence of strains of the same serovars differed significantly in piglets. Virulent and attenuated strains were present in all serovars, but serovar 5 was the most virulent in piglets, followed by serovars 13, 4, and 12. A significant difference in virulence was observed between serovars 5 and 4 and between serovars 5 and 12. However, the virulence of serovars 5 and 13 did not differ significantly. This comprehensive analysis of virulence in mice and piglets demonstrated that: (1) the order of virulence of the four domestic epidemic serovars (from strongest to weakest) in piglets was serovars 5, 13, 4, and 12; (2) both virulent and attenuated strains were present in all serovars, so virulence did not necessarily correlate with serovar; (3) Although was fatal in BALB/c mice, its virulence is inconsistent with that in piglets, indicating that BALB/c mice are inadequate as an alternative model of infection.
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http://dx.doi.org/10.3389/fvets.2021.659244DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8265781PMC
June 2021

Magnetic Resonance Neurography for Evaluation of Dorsal Root Ganglion Morphology.

World Neurosurg 2021 Jul 2. Epub 2021 Jul 2.

Department of Spine Surgery, Dongguan Tungwah Hospital, Dongguan, 523000, China.

Background: In this study, the morphological characteristics and anatomic position of the Dorsal Root Ganglion(DRG)were measured and analyzed in healthy people using Magnetic Resonance Neurography (MRN), providing an anatomical reference for minimally invasive spinal surgery.

Methods: From January 2018 to December 2019, 20 healthy adult volunteers (10 males and 10 females between 20-65 years old) were scanned and imaged by 3.0 T magnetic resonance imaging combined with neuroimaging technology. Here, the position of the DRG was located, and the shape and size of the DRG, as well as its distance to the upper pedicle, were measured.

Results: All volunteers obtained satisfactory MRN scans of the L1-S1 lumbar DRG. According to the spatial position of the DRG, the morphology of the DRG can be divided into Intervertebral Foramen type (81.01%), Intraspinal type (16.01%), Extraforaminal type (0.8%) and Mixed type (2.0%).

Conclusions: Intervertebral foramen type and Intraspinal type were observed to be the main distribution forms of lumbar DRG. Due to the downward movement of lumbar segments, the position of the DRG was noted to gradually move to the spinal canal while its volume gradually increased. Additionally, the distance from the upper pedicle was found to decrease gradually. MRN imaging can clearly show the shape, location and adjacent relationship of the DRG, providing effective imaging guidance for the minimally invasive lumbar techniques.
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http://dx.doi.org/10.1016/j.wneu.2021.06.123DOI Listing
July 2021

The clinical characteristics and prognosis of cytogenetically normal AML with single mutations of CEBPA.

Int J Lab Hematol 2021 Jul 3. Epub 2021 Jul 3.

Institute of Hematology, The Second Hospital of Shanxi Medical University, Taiyuan, China.

Introduction: CEBPA mutation is a common mutation in normal karyotype AML. CEBPAdm AML has been recognized as a separate entity, but there is still controversy to the prognosis of CEBPAsm patients.

Methods: A total of 151 newly diagnosed cytogenetically normal AML patients treated at the Second Hospital Center of Shanxi Medical University from February 2017 to December 2019 were the subjects of the study. According to the number of mutations in the CEBPA gene, the patients were divided into three groups, CEBPAsm, CEBPAdm, and CEBPAwt patients. The clinical characteristics, gene mutations, response, and prognosis were retrospectively compared among the three groups.

Results: CEBPAsm patients had lower hemoglobin values compared to CEBPAdm (P = .049). There was no statistical difference between the CEBPAsm cases and the CEBPAdm cases in the mutation types and the distribution of mutation regions (P > .050). Compared with CEBPAdm, cases with CEBPAsm were more likely associated with multiple other gene mutations (P = .023). Patients with CEBPAdm had a higher CR, ORR, and OS than those CEBPAwt (P < .050). CEBPAsm patients had a similar OS with CEBPAdm and CEBPAwt patients (P = .281). These CEBPAsm patients with VAF<30% had lower OS than the patients with VAF≥30%. FLT3-ITD mutations could reduce CEBPAsm patients' OS (P = .019).

Conclusion: Our data first highlighted the impact of CEBPAsm VAF on OS, and the results showed the lower the VAF was, the shorter the OS tended to. The VAF of CEBPAsm could provide specific significance in some extent for the prognosis of patients.
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http://dx.doi.org/10.1111/ijlh.13612DOI Listing
July 2021

Fault Diagnosis of a Wind Turbine Gearbox Based on Improved Variational Mode Algorithm and Information Entropy.

Entropy (Basel) 2021 Jun 23;23(7). Epub 2021 Jun 23.

School of Mechanical Engineering, Xinjiang University, Urumqi 830047, China.

The working environment of wind turbine gearboxes is complex, complicating the effective monitoring of their running state. In this paper, a new gearbox fault diagnosis method based on improved variational mode decomposition (IVMD), combined with time-shift multi-scale sample entropy (TSMSE) and a sparrow search algorithm-based support vector machine (SSA-SVM), is proposed. Firstly, a novel algorithm, IVMD, is presented for solving the problem where VMD parameters ( and ) need to be selected in advance, which mainly contains two steps: the maximum kurtosis index is employed to preliminarily determine a series of local optimal decomposition parameters ( and ), then from the local parameters, the global optimum parameters are selected based on the minimum energy loss coefficient (ELC). After decomposition by IVMD, the raw signal is divided into intrinsic mode functions (IMFs), the optimal IMF(s) with abundant fault information is (are) chosen based on the minimum envelopment entropy criterion. Secondly, the time-shift technique is introduced to information entropy, the time-shift multi-scale sample entropy algorithm is applied for the analysis of the complexity of the chosen optimal IMF and extract fault feature vectors. Finally, the sparrow search algorithm, which takes the classification error rate of SVM as the fitness function, is used to adaptively optimize the SVM parameters. Next, the extracted TSMSEs are input into the SSA-SVM model as the feature vector to identify the gear signal types under different conditions. The simulation and experimental results confirm that the proposed method is feasible and superior in gearbox fault diagnosis when compared with other methods.
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http://dx.doi.org/10.3390/e23070794DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8306640PMC
June 2021

Towards robust and understandable fault detection and diagnosis using denoising sparse autoencoder and smooth integrated gradients.

ISA Trans 2021 Jun 15. Epub 2021 Jun 15.

Department of Automation, Tsinghua University, Beijing, 100084, China. Electronic address:

Industrial applications of fault detection and diagnosis face great challenges as they require not only accurate identification of faulty statuses but also the effective understandability of the results. In this paper, a two-step robust and understandable fault detection and diagnosis framework is developed to address this challenge by exploiting denoising sparse autoencoder and smooth integrated gradients. Specifically, denoising sparse autoencoder(DSAE) is utilized to detect faults in the first step. DSAE is more robust to noise corruption and has better generalization performance compared to the existing autoencoder-based methods. In the second step, smooth integrated gradients(SIG) is used to diagnose the root-cause variables of the faults detected. Smooth integrated gradients can provide a denoising effect on the feature importance. The proposed framework is evaluated through an application to the Tennessee Eastman process. As proved in the experiments, the presented DSAE-SIG method not only achieves higher diagnosis accuracy but also successfully identifies the potential root-cause variables of process disturbances.
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http://dx.doi.org/10.1016/j.isatra.2021.06.005DOI Listing
June 2021

An integrative transcriptome study reveals Ddit4/Redd1 as a key regulator of cancer cachexia in rodent models.

Cell Death Dis 2021 Jun 26;12(7):652. Epub 2021 Jun 26.

State Key Laboratory of Analytical Chemistry for Life Science, Medical School of Nanjing University, Nanjing, P. R. China.

Cancer cachexia is a multifactorial metabolic syndrome that causes up to 20% of cancer-related deaths. Muscle atrophy, the hallmark of cancer cachexia, strongly impairs the quality of life of cancer patients; however, the underlying pathological process is still poorly understood. Investigation of the disease pathogenesis largely relies on cachectic mouse models. In our study, the transcriptome of the cachectic gastrocnemius muscle in the C26 xenograft model was integrated and compared with that of 5 more different datasets. The bioinformatic analysis revealed pivotal gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of the disease, and the key genes were validated. Construction of the protein-protein interaction network and the comparison of pathways enriched in cancer cachexia with 5 other muscle atrophy models revealed Ddit4 (DNA damage-inducible transcript 4), as a key protein in cancer cachexia. The higher expression of Ddit4 in cachectic muscle was further validated in animal models and cachectic cancer patients. Further study revealed that p38 induced the expression of Ddit4, which in turn inhibited the mTOR pathway in atrophic cells.
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http://dx.doi.org/10.1038/s41419-021-03932-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8236061PMC
June 2021

Inhibiting HDAC3 (Histone Deacetylase 3) Aberration and the Resultant Nrf2 (Nuclear Factor Erythroid-Derived 2-Related Factor-2) Repression Mitigates Pulmonary Fibrosis.

Hypertension 2021 Aug 21;78(2):e15-e25. Epub 2021 Jun 21.

From the Center for Organ Fibrosis and Remodeling Research, Jiangsu Key Lab of Molecular Medicine, Nanjing University School of Medicine, China.

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http://dx.doi.org/10.1161/HYPERTENSIONAHA.121.17471DOI Listing
August 2021

SENP1 modulates microglia-mediated neuroinflammation toward intermittent hypoxia-induced cognitive decline through the de-SUMOylation of NEMO.

J Cell Mol Med 2021 Jul 13;25(14):6841-6854. Epub 2021 Jun 13.

Department of Respiratory Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.

Intermittent hypoxia (IH)-induced cognition decline is related to the neuroinflammation in microglia. SUMOylation is associated with multiple human diseases, which can be reversed by sentrin/SUMO-specific proteases 1 (SENP1). Herein, we investigated the role of SENP1 in IH-induced inflammation and cognition decline. BV-2 microglial cells and mice were used for inflammatory response and cognition function evaluation following IH treatment. Biochemical analysis and Morris water maze methods were used to elaborate the mechanism of SENP1 in IH impairment. Molecular results revealed that IH induced the inflammatory response, as evidenced by the up-regulation of NF-κB activation, IL-1β and TNF-α in vitro and in vivo. Moreover, IH decreased the expression of SENP1, and increased the SUMOylation of NEMO, not NF-κB P65. Moreover, SENP1 overexpression inhibited IH-induced inflammatory response and SUMOylation of NEMO. However, the inhibitions were abolished by siRNA-NEMO. In contrast, SENP1 depletion enhanced IH-induced inflammatory response and SUMOylation of NEMO, accompanying with increased latency and reduced dwell time in mice. Overall, the results demonstrated that SENP1 regulated IH-induced neuroinflammation by modulating the SUMOylation of NEMO, thus activating the NF-κB pathway, revealing that targeting SENP1 in microglia may represent a novel therapeutic strategy for IH-induced cognitive decline.
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http://dx.doi.org/10.1111/jcmm.16689DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278079PMC
July 2021

Search for Light Dark Matter-Electron Scattering in the PandaX-II Experiment.

Phys Rev Lett 2021 May;126(21):211803

Research Center for Particle Science and Technology, Institute of Frontier and Interdisciplinary Science, Shandong University, Qingdao 266237, Shandong, China.

We report constraints on light dark matter through its interactions with shell electrons in the PandaX-II liquid xenon detector with a total 46.9  tonnes/day exposure. To effectively search for these very low energy electron recoils, ionization-only signals are selected from the data. 1821 candidates are identified within an ionization signal range between 50 and 75 photoelectrons, corresponding to a mean electronic recoil energy from 0.08 to 0.15 keV. The 90% C.L. exclusion limit on the scattering cross section between the dark matter and electron is calculated with systematic uncertainties properly taken into account. Under the assumption of point interaction, we provide the world's most stringent limit within the dark matter mass range from 15 to 30  MeV/c^{2}, with the corresponding cross section from 2.5×10^{-37} to 3.1×10^{-38}  cm^{2}.
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http://dx.doi.org/10.1103/PhysRevLett.126.211803DOI Listing
May 2021

Tissue- and stage-specific landscape of the mouse translatome.

Nucleic Acids Res 2021 06;49(11):6165-6180

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou 510060, China.

The current understanding of how overall principles of translational control govern the embryo-to-adult transition in mammals is still far from comprehensive. Herein we profiled the translatomes and transcriptomes of six tissues from the mice at embryonic and adult stages and presented the first report of tissue- and stage-specific translational landscape in mice. We quantified the extent of gene expression divergence among different expression layers, tissues and stages, detected significant changes in gene composition and function underlying these divergences and revealed the changing architecture of translational regulation. We further showed that dynamic translational regulation can be largely achieved via modulation of translational efficiency. Translational efficiency could be altered by alternative splicing (AS), upstream and downstream open reading frames (uORFs and dORFs). We revealed AS-mediated translational repression that was exerted in an event type-dependent manner. uORFs and dORFs exhibited mutually exclusive usage and the opposing effects of translational regulation. Furthermore, we discovered many novel microproteins encoded by long noncoding RNAs and demonstrated their regulatory potential and functional relevance. Our data and analyses will facilitate a better understanding of the complexity of translation and translational regulation across tissue and stage spectra and provide an important resource to the translatome research community.
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http://dx.doi.org/10.1093/nar/gkab482DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8216458PMC
June 2021

Chloroplast genome and phylogenetic analysis of .

Mitochondrial DNA B Resour 2021 May 27;6(6):1775-1776. Epub 2021 May 27.

College of Plant Protection, Henan Agricultural University, Zhengzhou, China.

is a potential medicinal and ornamental resource, and this study is the first to assemble the chloroplast genome of this species using high-throughput sequencing data. The chloroplast genome of has a typical composition for higher plant chloroplasts, containing one large single-copy region of 86,978 bp and one small single-copy region of 20,140 bp, which are separated by a pair of inverted-repeat regions of 25,473 bp. The chloroplast genome of this species encodes 130 genes, including 84 protein-coding genes, 38 tRNA genes and 8 rRNA genes. A maximum-likelihood phylogenetic tree was constructed based on sequence information of the chloroplast genomes. The chloroplast genome of will provide valuable genetic information for evolutionary research and utilization of this species.
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http://dx.doi.org/10.1080/23802359.2021.1932626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8168777PMC
May 2021

Association between IL-6 and severe disease and mortality in COVID-19 disease: a systematic review and meta-analysis.

Postgrad Med J 2021 Jun 3. Epub 2021 Jun 3.

The Respiratory Department, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China

Background: So far, SARS-CoV-2 is the seventh coronavirus found to infect humans and cause disease with quite a strong infectivity. Patients diagnosed as severe or critical cases are prone to multiple organ dysfunction syndrome, acute respiratory distress syndrome and even death. Proinflammatory cytokine IL-6 has been reported to be associated with the severity of disease and mortality in patients with COVID-19.

Objective: This systematic review and meta-analysis were carried out to evaluate the association between IL-6 and severe disease and mortality in COVID-19 disease.

Methods: A systematic literature search using China National Knowledge Infrastructure, Wanfang databases, China Science and Technology Journal Database, Chinese Biomedical Literature, Embase, PubMed and Cochrane Central Register of Controlled Trials was performed from inception until 16 January 2021.

Results: 12 studies reported the value of IL-6 for predicting the severe disease in patients with COVID-19. The pooled area under the curve (AUC) was 0.85 (95% CI 0.821 to 0.931). 5 studies elaborated the predictive value of IL-6 on mortality. The pooled sensitivity, specificity and AUC were 0.15 (95% CI 0.13 to 0.17, I=98.9%), 0.73 (95% CI 0.65 to 0.79, I=91.8%) and 0.531 (95% CI 0.451 to 0.612), respectively. Meta-regression analysis showed that country, technique used, cut-off, sample, study design and detection time did not contribute to the heterogeneity of mortality.

Conclusion: IL-6 is an adequate predictor of severe disease in patients infected with the COVID-19. The finding of current study may guide clinicians and healthcare providers in identifying potentially severe or critical patients with COVID-19 at the initial stage of the disease. Moreover, we found that only monitoring IL-6 levels does not seem to predict mortality and was not associated with COVID-19's mortality.

Prospero Registration Number: CRD42021233649.
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http://dx.doi.org/10.1136/postgradmedj-2021-139939DOI Listing
June 2021

LncRNA GAS5 Silencing Attenuates Oxygen-Glucose Deprivation/Reperfusion-Induced Injury in Brain Microvascular Endothelial Cells via miR-34b-3p-Dependent Regulation of EPHA4.

Neuropsychiatr Dis Treat 2021 26;17:1667-1678. Epub 2021 May 26.

Jiangsu Vocational College of Medicine, Yancheng, 224005, Jiangsu Province, People's Republic of China.

Background: The aim of our study was to explore the role of long non-coding RNA (lncRNA) growth arrest-specific 5 (GAS5) in ischemic stroke using oxygen-glucose deprivation/reperfusion (OGD/R)-induced bEnd.3 cells as in vitro cell model.

Methods: Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were adopted to analyze RNA and protein expression. Cell viability and apoptosis were analyzed by Cell Counting Kit-8 (CCK8) assay and flow cytometry. The levels of nitric oxide (NO) and endothelin-1 (ET-1) in culture supernatant were examined by their matching commercial kits. The intermolecular target interaction was predicted by starBase software and tested by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay.

Results: OGD/R-induced apoptosis and dysregulation in vascular endocrine system were largely alleviated by the knockdown of GAS5. GAS5 interacted with microRNA-34b-3p (miR-34b-3p), and GAS5 silencing protected bEnd.3 cells from OGD/R-induced injury partly through up-regulating miR-34b-3p. EPH receptor A4 (EPHA4) was a target of miR-34b-3p. GAS5 acted as the molecular sponge of miR-34b-3p to up-regulate EPHA4 in bEnd.3 cells. GAS5 interference protected against OGD/R-induced damage in bEnd.3 cells partly through down-regulating EPHA4.

Conclusion: LncRNA GAS5 knockdown protected brain microvascular endothelial cells bEnd.3 from OGD/R-induced injury depending on the regulation of miR-34b-3p/EPHA4 axis.
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http://dx.doi.org/10.2147/NDT.S302314DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8165656PMC
May 2021

Spatial and Temporal Characteristics of Hand-Foot-and-Mouth Disease and Their Influencing Factors in Urumqi, China.

Int J Environ Res Public Health 2021 05 5;18(9). Epub 2021 May 5.

College of Resources and Environmental Sciences, Xinjiang University, Urumqi 830046, China.

Hand, foot, and mouth disease (HFMD) remains a serious health threat to young children. Urumqi is one of the most severely affected cities in northwestern China. This study aims to identify the spatiotemporal distribution characteristics of HFMD, and explore the relationships between driving factors and HFMD in Urumqi, Xinjiang.

Methods: HFMD surveillance data from 2014 to 2018 were obtained from the China Center for Disease Control and Prevention. The center of gravity and geographical detector model were used to analyze the spatiotemporal distribution characteristics of HFMD and identify the association between these characteristics and socioeconomic and meteorological factors.

Results: A total of 10,725 HFMD cases were reported in Urumqi during the study period. Spatially, the morbidity number of HFMD differed regionally and the density was higher in urban districts than in rural districts. Overall, the development of HFMD in Urumqi expanded toward the southeast. Temporally, we observed that the risk of HFMD peaked from June to July. Furthermore, socioeconomic and meteorological factors, including population density, road density, GDP, temperature and precipitation were significantly associated with the occurrence of HFMD.

Conclusions: HFMD cases occurred in spatiotemporal clusters. Our findings showed strong associations between HFMD and socioeconomic and meteorological factors. We comprehensively considered the spatiotemporal distribution characteristics and influencing factors of HFMD, and proposed some intervention strategies that may assist in predicting the morbidity number of HFMD.
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http://dx.doi.org/10.3390/ijerph18094919DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8124546PMC
May 2021

The Effects of on Reproduction and Metabolism in Women with Polycystic Ovary Syndrome: A Systematic Review and Meta-Analysis.

Evid Based Complement Alternat Med 2021 15;2021:9971403. Epub 2021 May 15.

Department of Internal Medicine, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin 150040, China.

Objective: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age. As a traditional medicine, ( has been widely used in the treatment of many gynecological diseases, but the efficacy of in women with PCOS has not been assessed. The purpose of this systematic review and meta-analysis was to evaluate the effectiveness and safety of in women with PCOS.

Methods: We conducted searches in PubMed, Embase, the Cochrane Library, the China National Knowledge Infrastructure, the Wanfang Database, the Chinese Scientific Journal Database, and the Chinese BioMedical database from inception to December 23, 2020, to identify studies that met the inclusion criteria. The quality of the evidence was estimated using the Cochrane Reviewer Handbook 5.0.0, and the meta-analysis was performed using RevMan 5.3.5 software.

Results: Six randomized controlled trials (RCTs) involving 390 patients with PCOS were included. The studies suggested that extract combined with letrozole (LET) was more effective in improving pregnancy rate (RR: 2.60, 95% CI: 1.06 to 6.39, =0.04) compared to LET alone. extract was associated with decreased fasting blood glucose (MD: -0.25, 95% CI: -0.37 to -0.13, < 0.0001), fasting insulin (MD: -1.16, 95% CI: -1.74 to -0.58, < 0.0001), total cholesterol (TC) (MD: -0.58, 95% CI: -0.72 to -0.43, < 0.00001), and triglycerides (TG) (MD: -0.31, 95% CI: -0.35 to -0.26, < 0.00001) compared with placebo, but not with improvements in body mass index or waist-to-hip ratio (MD: -1.41, 95% CI: -4.81 to 2.00, =0.42; MD: -0.02, 95% CI: -0.05 to 0.01, =0.16, respectively). There was a significant difference between extract combined with cyproterone acetate (CPA) and CPA alone in terms of decreasing TC (MD: -0.77, 95% CI: -0.89 to -0.65, < 0.00001), TG (MD: -0.43, 95% CI: -0.65 to -0.20, < 0.0001), and low-density lipoprotein cholesterol (MD: -0.49, 95% CI: -0.66 to -0.33, < 0.00001) and increasing high-density lipoprotein cholesterol (MD: 0.30, 95% CI: 0.20, 0.40, < 0.00001). In addition, extract also decreased testosterone, follicle-stimulating hormone, and luteinizing hormone. The studies did not mention any adverse events with extract.

Conclusion: The current studies indicate that has beneficial effects on reproduction and glucose and lipid metabolism in patients with PCOS, and it is generally safe for clinical application. However, more prospective RCTs with large samples, multiple centers, and longer intervention duration are needed in the future to obtain more reliable conclusions.
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http://dx.doi.org/10.1155/2021/9971403DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8143891PMC
May 2021

PERK-eIF2α-ERK1/2 axis drives mesenchymal-endothelial transition of cancer-associated fibroblasts in pancreatic cancer.

Cancer Lett 2021 Sep 28;515:86-95. Epub 2021 May 28.

Department of Pancreatic Cancer, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin's Clinical Research Center for Cancer, Tianjin 300060, PR China. Electronic address:

Pancreatic ductal adenocarcinoma (PDAC) is characterized by remarkable desmoplasia, usually driven by cancer-associated fibroblasts (CAFs), influencing patient prognosis. CAFs are a group of plastic cells responsible for tumor growth and metastasis. Fibroblasts have been reported to directly contribute to angiogenesis by undergoing mesenchymal-endothelial transition (MEndoT) after ischemic injury in the heart, brain, and hindlimbs. However, whether CAFs can undergo similar transdifferentiation in the hostile tumor microenvironment and directly contribute to tumor angiogenesis remains unclear. Herein, we provide evidence that CAFs can adopt an endothelial cell-like phenotype and directly contribute to tumor angiogenesis in vitro and in vivo. Furthermore, this program is regulated by the PERK-eIF2α-ERK1/2 axis. Pharmacological inhibition of PERK with GSK2606414 limited the phenotypic transition of CAFs. In conclusion, our results suggest that CAFs contribute to tumor angiogenesis by undergoing the MEndoT, thus representing therapeutic targets for improving PDAC prognosis.
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http://dx.doi.org/10.1016/j.canlet.2021.05.021DOI Listing
September 2021

Depletion of SENP1-mediated PPARγ SUMOylation exaggerates intermittent hypoxia-induced cognitive decline by aggravating microglia-mediated neuroinflammation.

Aging (Albany NY) 2021 05 25;13(11):15240-15254. Epub 2021 May 25.

Department of Respiratory Medicine, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.

Intermittent hypoxia (IH)-associated cognition decline is related to the neuroinflammation of microglia. SUMOylation is a post-translational modification related to multiple human diseases, which can be reversed by SENP1. Studies showed that SENP1 and PPARγ play essential roles in restricting inflammation by blocking NF-κB activation. However, the mechanism remains unclear. Herein, we investigated the precise mechanism underlying SENP1 and PPARγ in cognitive decline after IH insult. Biochemical analysis results revealed that IH triggered the inflammatory response and neuronal apoptosis, increased the SUMOylation of PPARγ, and decreased the level of PPARγ compared to that in the normoxia group. After SENP1 downregulation, the inflammatory response, neuronal apoptosis and the SUMOylation of PPARγ were enhanced, and the level of PPARγ was further decreased and . However, the application of PPARγ agonist, GW1929, abolished the enhancement of inflammation and neuronal apoptosis . The Morris Water Maze results showed that both IH groups mice exhibited longer latency and shorter dwell-time in the goal quadrant than normoxia groups. Notably, SENP1 downregulation aggravated these alterations. Overall, these results showed that SENP1 played an essential role in IH-associated cognitive dysfunction. SENP1 depletion aggravated neuroinflammation and neuronal apoptosis via promoting the SUMOylation of PPARγ, reducing the level of PPARγ, thus exaggerating IH-induced cognitive decline.
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http://dx.doi.org/10.18632/aging.203084DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8221356PMC
May 2021

MicroRNA-146a-3p/HDAC1/KLF5/IKBα signal axis modulates plaque formation of atherosclerosis mice.

Life Sci 2021 May 15:119615. Epub 2021 May 15.

Department of Cardiology, Fengxian District Central Hospital, Shanghai, China.

Background: Atherosclerosis (AS) is a multifocal, smoldering immune inflammatory disease of medium and large arteries driven by lipids. The aim of this study is to discuss the mechanism of microRNA-146a-3p (miR-146a-3p)/histone deacetylase 1 (HDAC1)/Krüppel-like factor 5 (KLF5)/inhibitors of kappa B α (IKBα) signal axis in plaque formation of AS mice.

Methods: ApoE mice were fed with high-fat feed for 12 weeks to establish AS mice model. The expression of miR-146a-3p, KLF5, HDAC1 and IKBα in aortic wall tissues of AS mice was tested. The targeting relationship between miR-146a-3p and HDAC1 was verified. AS mice were injected with miR-146a-3p antagomir or HDAC1 overexpression to verify the impacts of miR-146a-3p and HDAC1 on blood lipids and inflammatory factors in serum, aortic wall apoptotic cells, antioxidant stress capacity and the plaque area in AS mice. VECs proliferation and apoptosis were also measured in vitro.

Results: miR-146a-3p and KLF5 were increased while HDAC1 and IKBα were reduced in aortic wall tissues of AS mice. miR-146a-3p directly targeted to HDAC1. Depletion of miR-146a-3p or restoration of HDAC1 was correlated to lower plasma lipid level, reduced inflammatory factors in serum, attenuated aortic wall apoptosis, increased antioxidant stress capacity and improved the stability of pathological plaque of AS mice. miR-146a-3p down-regulation or HDAC1 up-regulation promoted VECs proliferation and inhibited apoptosis.

Conclusion: Functional studies show that depleted miR-146a-3p advances HDAC1 and IKBα expression as well as inhibits KLF5 expression to facilitate the stability of pathological plaques in AS mice.
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http://dx.doi.org/10.1016/j.lfs.2021.119615DOI Listing
May 2021

Characterization and phylogenetic analysis of the chloroplast genome of var. .

Mitochondrial DNA B Resour 2021 Apr 27;6(4):1490-1491. Epub 2021 Apr 27.

College of Plant Protection, Henan Agricultural University, Zhengzhou, China.

var. is a well-regarded ornamental plant in the genus (family Iridaceae). In this report, we present the complete chloroplast (cp) genome sequence of var. for the first time. The complete cp genome of var. was assembled using high-throughput sequencing, and phylogenetic analysis was undertaken based on a dataset of coding regions. The cp genome of var. measures 152,409 bp in length, with regions having two inverted copies (IR 26,026 bp), and separated by the large single copy (LSC 82,256 bp) and small single copy (SSC 18,101 bp) regions. The cp genome encodes 133 unique genes, including 87 different protein-coding genes, 38 tRNA genes, and 8 rRNA genes. Based on a dataset of 69 chloroplast coding regions, the maximum-likelihood (ML) phylogenetic tree analysis indicated that var. clusters closely with . Thus, the complete chloroplast genome presented in this report may provide valuable genetic information not only for the future exploitation and utilization of this plant resource but also for further research investigating its relationship with other species.
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http://dx.doi.org/10.1080/23802359.2020.1847611DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8081313PMC
April 2021

Chinese guidelines on the clinical application of 5-aminolevulinic acid-based photodynamic therapy in dermatology (2021 edition).

Photodiagnosis Photodyn Ther 2021 May 12;35:102340. Epub 2021 May 12.

Institute of Photomedicine, Shanghai Skin Disease Hospital, School of Medicine, Tongji University, Shanghai, China. Electronic address:

Photodynamic Therapy with 5-aminolevulinic acid (ALA-PDT) has been widely applied in the treatment of skin diseases in China. To further standardize, guide, and promote the clinical applications of ALA-PDT in dermatology, the Chinese Society of Dermatology, Chinese Association of Rehabilitation Dermatology, Photomedicine Therapeutic Equipment Group of Committee on Skin Disease, and Cosmetic Dermatology of China Association of Medical Equipment invited relevant experts engaged in ALA-PDT to revise and update the first edition of "Clinical application of 5-aminolevulinic acid-based photodynamic therapy: an expert consensus statement" and establish a more current edition, to provide an updated reference for Chinese dermatologists in clinical practice. In the guideline, the expert group reached consensus opinions on ALA-PDT with regard to mechanisms of action, therapeutic protocol, clinical applications, adverse reactions and countermeasures, precautions, care, and evaluation of efficacy.
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http://dx.doi.org/10.1016/j.pdpdt.2021.102340DOI Listing
May 2021

A moderated mediation model linking transactive memory system and social media with shared leadership and team innovation.

Scand J Psychol 2021 Aug 14;62(4):625-637. Epub 2021 May 14.

School of Economics and Business Administration, Yibin University, Yibin, P.R. China.

This study examines how and to what extent social and technological factors promote shared leadership that leads to team innovation in knowledge work teams. It hypothesizes that a transactive memory system influence team innovation and shared leadership conduits the relationship between them. Additionally, the relationship effectiveness between the transactive memory system and shared leadership increases with the use of social media by team members. Time-lagged, multi-sourced data are collected from the information technology industry in China. In addition, we used a network-based measure to assess the level of shared leadership in teams. Empirical analysis found support for the hypotheses of this study. The results reveal that transactive memory system is a significant predictor of team innovation and the shared leadership channels the relationship between transactive memory system and team innovation. Furthermore, use of social media by team members amplifies the relationship between transactive memory system and shared leadership. The implications of the study are discussed in the later sections.
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http://dx.doi.org/10.1111/sjop.12733DOI Listing
August 2021

Short- and long-term outcomes of hepatectomy combined with intraoperative radiofrequency ablation for patients with multiple primarily unresectable colorectal liver metastases: a propensity matching analysis.

HPB (Oxford) 2021 Apr 18. Epub 2021 Apr 18.

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Hepato-biliary-pancreatic Surgery I, Peking University Cancer Hospital & Institute, China. Electronic address:

Background: Hepatectomy combined with intraoperative radiofrequency ablation (IORFA) is a strategy to eliminate all tumors in patients with multiple colorectal liver metastases (CRLM). This study aimed to evaluate the surgical and oncological outcomes of hepatectomy + IORFA for multiple unresectable CRLM.

Methods: We included patients who underwent combined hepatectomy and IORFA for multiple unresectable CRLM (n = 67) or hepatectomy alone (n = 268) for CRLM. Patients were matched in a 1:1 propensity score analysis to compare the short- and long-term outcomes between groups.

Results: Patients in hepatectomy + IORFA group had a median number of 10 liver lesions. Postoperative morbidity and the rate of major complications was similar between groups (P = 0.362, P = 1.000). The median overall survival (OS), progression free survival (PFS) and hepatic recurrence free survival (HRFS) was similar between groups (3-year OS: 54.2% versus 60.9%, P = 0.389; 3-year PFS: 7.9% versus 19.6%, P = 0.148; 3-year HRFS: 16.7% versus 31.5%, P = 0.202). Re-hepatectomy or radiofrequency ablation was used to treat 47.5% of hepatic recurrences, and the median OS was significantly higher than for patients treated with systemic treatment alone (P < 0.001).

Conclusions: Combining hepatectomy and IORFA could provide comparable survival rates for patients with multiple unresectable CRLM compared to those with resectable CRLM treated with hepatectomy alone.
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http://dx.doi.org/10.1016/j.hpb.2021.03.014DOI Listing
April 2021

Preparative separation and purification of loliolide and epiloliolide from Ascophyllum nodosum using amine-based microporous organic polymer for solid phase extraction coupled with macroporous resin and prep-HPLC.

Anal Methods 2021 04 8;13(16):1939-1944. Epub 2021 Apr 8.

State Key Laboratory Cultivation Base, Shandong Provincial Key Laboratory of Ophthalmology, Shandong Eye Institute, Shandong First Medical University, Shandong Academy of Medical Sciences, Qingdao 266071, China.

Herein, we reported a novel approach for the preparative separation and purification of loliolide and epiloliolide from Ascophyllum nodosum. An amine-based microporous organic polymer (MOP) was used for the pretreatment of the nodosum extract via solid-phase extraction (SPE). The obtained extract was further purified using macroporous resin chromatography and preparative high-performance liquid chromatography (prep-HPLC). The loading and elution parameters of the MOP were evaluated using standard loliolide, and the optimized conditions were used during the SPE of the nodosum extract (37.5 g). After the pretreatment with MOP, the extract (2.79 g) was obtained and further purified using a D101 resin column followed by prep-HPLC. A pair of epimers were isolated and identified as loliolide (5.83 mg) and epiloliolide (2.50 mg) using high-resolution electrospray ionization tandem mass spectrometry (HRESI-MS), 1D- and 2D-nuclear magnetic resonance (NMR) spectroscopy. This study demonstrates the potential of MOPs in the separation and purification of monoterpenoids from complex plant samples.
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http://dx.doi.org/10.1039/d1ay00186hDOI Listing
April 2021

Sub-Nanometer Nanobelts Based on Titanium Dioxide/Zirconium Dioxide-Polyoxometalate Heterostructures.

Adv Mater 2021 Jun 27;33(23):e2100576. Epub 2021 Apr 27.

Key Lab of Organic Optoelectronics and Molecular Engineering, Department of Chemistry, Tsinghua University, Beijing, 100084, China.

In addition to offering conformational flexibility, sub-nanometer nanobelts (SNBs) also outperform many larger nanobelts with large size owing to their ultrathin morphologies. However, to date, only a few monocomponent SNBs have been synthesized. This study presents a facile method for synthesizing ZrO -PMoO (PMZ) SNBs and TiO -PMoO (PMT) SNBs with heterostructures. The SNBs comprise ZrO /TiO and polyoxometalate (POM) nanoclusters, which are formed via the aggregation and subsequent transformation of nanoclusters. Significantly, these SNBs demonstrate high catalytic activity and stability in oxidative desulfurization reactions at room temperature. The impressive catalytic performance of the SNBs is aided by the POM nanoclusters, which not only coassemble with ZrO /TiO nuclei to form building blocks of PMZ SNBs/PMT SNBs but also serve as catalytic centers. The catalytic performance is further enhanced by the ZrO /TiO in the SNBs. Moreover, the proposed synthesis method can be utilized to produce other SNBs. Thus, this method provides valuable insights into the strong performance properties of SNBs created by combining metal oxides and POM nanoclusters into SNBs, which have great potential as redox catalysts.
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http://dx.doi.org/10.1002/adma.202100576DOI Listing
June 2021

A lineage switch from NPM1-mutant acute myeloid leukemia to acute T-cell lymphoblastic leukemia with KMT2D and ARID2 mutant.

Int J Lab Hematol 2021 Apr 21. Epub 2021 Apr 21.

The Haematology Department, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China.

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http://dx.doi.org/10.1111/ijlh.13534DOI Listing
April 2021

Analysis of Risk Factors for Thromboembolic Events in 88 Patients with COVID-19 Pneumonia in Wuhan, China: A Retrospective Descriptive Report.

Med Sci Monit 2021 Apr 11;27:e929708. Epub 2021 Apr 11.

Department of Respiratory and Critical Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China (mainland).

BACKGROUND Since the outbreak of COVID-19 in December 2019, there have been 96 623 laboratory-confirmed cases and 4784 deaths by December 29 in China. We aimed to analyze the risk factors and the incidence of thrombosis from patients with confirmed COVID-19 pneumonia. MATERIAL AND METHODS Eighty-eight inpatients with confirmed COVID-19 pneumonia were reported (31 critical cases, 33 severe cases, and 24 common cases). The thrombosis risk factor assessment, laboratory results, ultrasonographic findings, and prognoses of these patients were analyzed, and compared among groups with different severity. RESULTS Nineteen of the 88 cases developed DVT (12 critical cases, 7 severe cases, and no common cases). In addition, among the 18 patients who died, 5 were diagnosed with DVT. Positive correlations were observed between the increase in D-dimer level (≥5 µg/mL) and the severity of COVID-19 pneumonia (r=0.679, P<0.01), and between the high Padua score (≥4) and the severity (r=0.799, P<0.01). In addition, the CRP and LDH levels on admission had positive correlations with the severity of illness (CRP: r=0.522, P<0.01; LDH: r=0.600, P<0.01). A negative correlation was observed between the lymphocyte count on admission and the severity of illness (r=-0.523, P<0.01). There was also a negative correlation between the lymphocyte count on admission and mortality in critical patients (r=-0.499, P<0.01). Univariable logistic regression analysis showed that the occurrence of DVT was positively correlated with disease severity (crude odds ratio: 3.643, 95% CI: 1.218-10.896, P<0.05). CONCLUSIONS Our report illustrates that critically or severely ill patients have an associated high D-dimer value and high Padua score, and illustrates that a low threshold to screen for DVT may help improve detection of thromboembolism in these groups of patients, especially in asymptomatic patients. Our results suggest that early administration of prophylactic anticoagulant would benefit the prognosis of critical patients with COVID-19 pneumonia and would likely reduce thromboembolic rates.
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http://dx.doi.org/10.12659/MSM.929708DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8047776PMC
April 2021

Soluble IL-6R-mediated IL-6 trans-signaling activation contributes to the pathological development of psoriasis.

J Mol Med (Berl) 2021 Jul 9;99(7):1009-1020. Epub 2021 Apr 9.

Center for Translational Medicine, State Key Laboratory of Analytical Chemistry for Life Science & Jiangsu Key Laboratory of Molecular Medicine, Medical School, Nanjing University, Nanjing, 210093, People's Republic of China.

IL-6 has been suggested to function as an autocrine mitogen in the psoriatic epidermis. The biological activity of IL-6 relies on interactions with its receptors, including the membrane-bound IL-6 receptor (mIL-6R) and soluble IL-6 receptor (sIL-6R). Our study presents data showing that the levels of plasma IL-6 and sIL-6R were elevated in psoriatic patients. Genotyping of two single-nucleotide polymorphisms (SNPs) in IL-6R (rs4845617 and rs2228145) demonstrated that the SNP IL-6R (rs4845617) rather than IL-6R (rs2228145) shows a significant association with psoriasis (P = 0.006). To verify the functions of sIL-6R, cultured keratinocytes and imiquimod (IMQ)-induced psoriatic model mice were treated with sIL-6R. We found that the presence of sIL-6R in the HaCaT cell culture medium enhanced the IL-6-induced Stat3 activation, which resulted in abnormal keratinocyte proliferation and aberrant differentiation. Furthermore, the application of sIL-6R in vivo accelerated the pathological development of the disease. Our results demonstrate for the first time that genetic polymorphisms in the IL-6R gene are associated with psoriasis disease phenotypes in a Chinese psoriatic patient population; sIL-6R-mediated trans-signaling pathway plays a pivotal role in keratinocyte proliferation and differentiation, suggesting potential therapeutics for psoriasis. KEY MESSAGES: Patients with psoriasis displayed higher levels of IL-6 and sIL-6R compared with healthy controls. Analysis of genotypes revealed that IL-6R rs4845617 GG genotype associated with the risk of psoriasis. Supplement of sIL-6R further enhanced IL-6-induced Stat3 activation in keratinocytes. In vivo administration of sIL-6R accelerated, whereas sgp130FC alleviated, the pathological development of psoriasis.
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http://dx.doi.org/10.1007/s00109-021-02073-3DOI Listing
July 2021
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