Publications by authors named "Siqing Wang"

56 Publications

Compatibility Optimal Design of Axially Loaded Circular Concrete-Filled Steel Tube Stub Columns.

Materials (Basel) 2021 Aug 26;14(17). Epub 2021 Aug 26.

National Engineering Laboratory for High Speed Railway Construction, Changsha 410075, China.

Numerous studies have been carried out on the axially loaded circular concrete-filled steel tube (CCFST) stub columns. However, to date, no clear evaluation criterion for the compatibility of its design parameters has been established. In the present study, the compatibility of the design parameters (concrete compressive strength fc, steel yield strength fy, diameter and thickness of steel tube ) of axially loaded CCFST stub columns was quantitatively investigated in terms of the contribution of the composite actions to the axial bearing capacity of the columns. The composite ratio λ was proposed as an indicator to represent the effectiveness of the composite actions. A numerical framework of the determination of λ was established, making use of a series of existing widely recognized constitutive models of structural steel and concrete. Some modifications were carried out on these models to ensure the numerical stability of the presented analysis. Moreover, the rationality of the combined use of these models was verified. The analytical results show that excessive or very small D/t ratio should be avoided in design. Meanwhile, the combined use of low-strength steel and high-strength concrete should be avoided. A table of optimal D/t ratios corresponding to different material strength matches was provided for designers. Finally, an optimization of the design parameters using the proposed method and the existing design specification was performed.
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http://dx.doi.org/10.3390/ma14174839DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8432730PMC
August 2021

Typhoon-induced turbulence redistributed microplastics in coastal areas and reformed plastisphere community.

Water Res 2021 Aug 19;204:117580. Epub 2021 Aug 19.

School of Environmental Science and Engineering, College of Engineering, Southern University of Science and Technology, Shenzhen 518055, China; State Environmental Protection Key Laboratory of Integrated Surface Water-Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China; Guangdong Provincial Key Laboratory of Soil and Groundwater Pollution Control, School of Environmental Science and Engineering, Southern University of Science and Technology, Shenzhen 518055, China. Electronic address:

The increasing microplastic pollution together with the plastisphere-associated ecological threats in coastal areas have aroused global concern. Tropical cyclones have been increased in both frequency and intensity under global warming, causing intense impact on the microplastics distribution and the structure of coastal ecosystems. However, until most currently, the extent to which typhoon impacts the microplastics and plastisphere community remains poorly known. This study analyzed the effects of Typhoon Wipha (Code: 1907) on microplastics abundance and composition in surface water and sediment crossed coastal areas of Shenzhen. Here we found a significant typhoon-induced increase in microplastics abundance in surface water, whereas an opposite trend was observed in sediment. Despite the evident transportation of microplastics from sediment to surface water by agitation, a possible microplastics influx was introduced by typhoon as evidenced by the large attribution of unknown force in source tracking analysis. Furthermore, typhoon had adeptly uniformed the plastisphere community in the sediment along the 190 km costal line overnight. A significant increase of nitrogen fixer, Bradyrhizobiaceae, was observed ubiquitously after typhoon, which might alter the nitrogen cycling and increase eutrophic condition of the coastal ecological system. Together, this study expanded the knowledge about the impact of typhoon-induced influx of the microplastics on coastal biogeochemical cycling. Moreover, the microplastics and the plastisphere compositional pattern revealed here will underpin future studies on adsorption behavior, interfacial processes and ecotoxicity of the coastal microplastic pollution.
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http://dx.doi.org/10.1016/j.watres.2021.117580DOI Listing
August 2021

High Neutrophil-To-Lymphocyte Ratio Is an Independent Risk Factor for End Stage Renal Diseases in IgA Nephropathy.

Front Immunol 2021 12;12:700224. Epub 2021 Aug 12.

West China School of Medicine, Sichuan University, Chengdu, China.

Background: Complex factors are involved in the development and progression of immunoglobulin A nephropathy (IgAN), a common primary glomerulonephritis worldwide. Autoimmunity and inflammation have been considered to be the basic mechanisms; however, the exact pathogenesis remains unclear. As a novel marker of inflammation, the neutrophil-to-lymphocyte ratio (NLR) has been studied in various diseases. Whether the NLR can predict the renal outcome of patients with IgAN remains unclear. We evaluated the relationships between the NLR and renal function, pathologic lesions, renal progression, and prognosis in patients with IgAN.

Methods: This retrospective study involved 966 patients with biopsy-proven IgAN. They were divided into two groups based on the cut-off value of the NLR: the high group (NLR ≥ 2.67, n = 384) and the low group (NLR < 2.67, n = 582). The endpoint was end-stage renal disease [estimated glomerular filtration rate (eGFR) of <15 mL/min/1.73 m or performance of renal replacement therapy]. A correlation test was conducted to explore the relationship between the NLR and other important parameters (eGFR, serum creatinine, proteinuria, hypertension and renal pathologic lesions). The predictive value was determined by the area under the receiver operating characteristics curve (AUROC). Kaplan-Meier and Cox proportional hazards analyses were performed to evaluate renal progression and prognosis.

Results: The NLR had the highest AUROC, which was 0.633 (p < 0.001). The correlation test revealed that the NLR was positively correlated with serum creatinine (r = 0.127, p < 0.001) and 24-hour urine protein (r = 0.18, p < 0.001) and negatively correlated with eGFR (r = 0.14, p < 0.001). Patients with IgAN who had a high NLR were more likely to have hypertension (p = 0.003). Multivariate Cox regression analysis indicated that a high NLR was an independent risk factor for IgAN even after adjustment for important clinical and pathological parameters (p = 0.043, HR = 1.74, 95%CI: 1.02-2.97). Kaplan-Meier analysis showed that a high NLR was significantly associated with the renal prognosis of patients with IgAN (p < 0.001), especially patients with stage 3 to 4 chronic kidney disease (p = 0.028) or 24-hour urine protein of >1 g/day (p < 0.001).

Conclusion: An elevated NLR affects the renal progression and prognosis in patients with IgAN and could be a marker for evaluation of renal function and pathologic lesions.
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http://dx.doi.org/10.3389/fimmu.2021.700224DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8387559PMC
August 2021

KDM5A suppresses PML-RARα target gene expression and APL differentiation through repressing H3K4me2.

Blood Adv 2021 09;5(17):3241-3253

Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, China; and.

Epigenetic abnormalities are frequently involved in the initiation and progression of cancers, including acute myeloid leukemia (AML). A subtype of AML, acute promyelocytic leukemia (APL), is mainly driven by a specific oncogenic fusion event of promyelocytic leukemia-RA receptor fusion oncoprotein (PML-RARα). PML-RARα was reported as a transcription repressor through the interaction with nuclear receptor corepressor and histone deacetylase complexes leading to the mis-suppression of its target genes and differentiation blockage. Although previous studies were mainly focused on the connection of histone acetylation, it is still largely unknown whether alternative epigenetics mechanisms are involved in APL progression. KDM5A is a demethylase of histone H3 lysine 4 di- and tri-methylations (H3K4me2/3) and a transcription corepressor. Here, we found that the loss of KDM5A led to APL NB4 cell differentiation and retarded growth. Mechanistically, through epigenomics and transcriptomics analyses, KDM5A binding was detected in 1889 genes, with the majority of the binding events at promoter regions. KDM5A suppressed the expression of 621 genes, including 42 PML-RARα target genes, primarily by controlling the H3K4me2 in the promoters and 5' end intragenic regions. In addition, a recently reported pan-KDM5 inhibitor, CPI-455, on its own could phenocopy the differentiation effects as KDM5A loss in NB4 cells. CPI-455 treatment or KDM5A knockout could greatly sensitize NB4 cells to all-trans retinoic acid-induced differentiation. Our findings indicate that KDM5A contributed to the differentiation blockage in the APL cell line NB4, and inhibition of KDM5A could greatly potentiate NB4 differentiation.
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http://dx.doi.org/10.1182/bloodadvances.2020002819DOI Listing
September 2021

The association of atherosclerotic cardiovascular disease and statin use with inflammation and treatment outcomes in tuberculosis.

Sci Rep 2021 Jul 27;11(1):15283. Epub 2021 Jul 27.

Division of Infectious Diseases, Department of Medicine, Johns Hopkins School of Medicine, Koch Cancer Research Building, 1550 Orleans St., Room 110, Baltimore, MD, 21287, USA.

Tuberculosis (TB) and atherosclerotic cardiovascular disease (ASCVD) have a close epidemiological and pathogenetic overlap. Thus, it becomes essential to understand the relationship between ASCVD and TB outcomes. From our retrospective cohort on drug-susceptible TB patients at the National Taiwan University Hospital, we assessed the association of pre-existing ASCVD (coronary artery disease (CAD) and atherothrombotic stroke (ATS)) with 9-month all-cause and infection-related mortality and the extent of mediation by systemic inflammatory markers. We determined the effect of pre-existing ASCVD on 2-month sputum microbiological status. Among ASCVD patients, we assessed the association of statin use on mortality. Nine-month all-cause mortality was higher in CAD patients with prior acute myocardial infarction (CADAMI) (adjusted HR 2.01, 95%CI 1.38-3.00) and ATS patients (aHR 2.79, 95%CI 1.92-4.07) and similarly, for infection-related mortality was higher in CADAMI (aHR 1.95, 95%CI 1.17-3.24) and ATS (aHR 2.04, 95%CI 1.19-3.46) after adjusting for confounding factors. Pre-existing CAD (AMI or AMI) or ATS did not change sputum culture conversion or sputum smear AFB positivity at 2 months. The CADAMI group had significantly higher levels of CRP at TB diagnosis in the multivariable linear regression analysis (Adjusted B(SE) 1.24(0.62)). CRP mediated 66% (P = 0.048) and 25% (P = 0.033) of the association all-cause mortality with CADAMI and CADAMI, respectively. In summary, patients with ASCVD have higher hazards of 9-month all-cause and infection-related mortality, with elevated serum inflammation mediating one to three-quarters of this association when adjusted for confounders. Statin use was associated with lower all-cause mortality among patients with ASCVD.
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http://dx.doi.org/10.1038/s41598-021-94590-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316554PMC
July 2021

Lower serum bilirubin is associated with poor renal outcome in IgA nephropathy patients.

Int J Med Sci 2021 11;18(13):2964-2970. Epub 2021 Jun 11.

Division of Nephrology, Department of Medicine, West China Hospital of Sichuan University.

: IgA nephropathy (IgAN) is the most prevalent primary glomerulonephritis worldwide. We conducted this study to explore the relationship between serum bilirubin and renal outcome of patients with IgAN. : A total of 1492 biopsy proven IgAN patients were recruited and divided into two groups according to their median serum bilirubin concentration: the low bilirubin group (serum bilirubin≤9.7umol/L, n=753) and high bilirubin group (serum bilirubin>9.7umol/L, n=739). Basic clinical characteristics were assessed at the time of renal biopsy and the relationships between serum bilirubin and the combined endpoints were analyzed. The combined endpoints were defined as a 50% decline in estimate glomerular filtration rate (e-GFR), end-stage kidney disease (ESKD), renal transplantation and/or death. In addition, propensity score matching (PSM) was then performed to improve balance and simulate randomization between patients in different groups. Kaplan-Meier survival analysis was applied to explore the role of serum bilirubin in the progression of IgAN. Three clinicopathological models of multivariate Cox regression analysis were established to evaluate the association of serum bilirubin and renal prognosis of IgAN. During median 5-year follow-up period, significant differences were shown in Kaplan-Meier analysis. In the unmatched group, 189 (12.7%) patients progressed to the renal combined endpoints. Among this, 122 in 753 patients (16.2%) were in low bilirubin group and 67 in 739 patients (9.1%) were in high bilirubin group (p<0.001). After PSM, there were 134 (11.8%) patients reached the combined endpoints, which included 77 in 566 patients (14.6%) in low bilirubin group and 57 in 566 patients (10.1%) in high bilirubin group (p=0.039). The results of three models (including demographics, pathological, clinical indicators and serum bilirubin) demonstrated that a lower basic serum bilirubin level was significantly associated with a higher risk of reaching combined endpoints in IgAN patients both in unmatched and matched cohort. : Serum bilirubin level may be negatively associated with the progression of IgAN.
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http://dx.doi.org/10.7150/ijms.60111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241783PMC
June 2021

Cigarette smoking may accelerate the progression of IgA nephropathy.

BMC Nephrol 2021 Jun 29;22(1):239. Epub 2021 Jun 29.

West China School of Medicine, Sichuan University, Chengdu, Sichuan, China.

Background: Whether cigarette smoking is associated with the progression of immunoglobulin A nephropathy (IgAN) remains uncertain; therefore, we aimed to evaluate the effect of cigarette smoking on the prognosis of IgAN.

Methods: We divided 1239 IgAN patients from West China Hospital of Sichuan University who met the inclusion criteria into smoker (current or former) and non-smoker groups. The endpoint was end-stage renal disease (ESRD: eGFR < 15 mL/min/1.73 m or undergoing renal replacement treatment) and/or eGFR decreased by > 50%. Kaplan-Meier, correlation, logistic regression and Cox proportional hazards analyses were performed. The association between cigarette smoking and IgAN was further verified by propensity-score-matched cohort analysis.

Results: During the mean follow-up period of 61 months, 19% (40/209) of the smoker group and 11% (110/1030) of the non-smoker group reached the study endpoint (p < 0.001). Multivariate Cox regression analysis revealed that cigarette smoking (hazard ratio (HR) = 1.58; p = 0.043) was an independent risk factor predicting poor renal progression in IgAN, and that IgAN patients with chronic kidney disease (CKD) stage 3-4 were more susceptible to cigarette smoking (p < 0.001). After propensity score matching (PSM), a significant correlation between cigarette smoking and renal outcomes in IgAN patients was seen. Furthermore, Spearman's correlation test revealed that smoking dose was negatively correlated with eGFR (r = 0.141; p < 0.001) and positively related with proteinuria (r = 0.096; p = 0.001).

Conclusions: Cigarette smoking is an independent risk factor for IgAN progression, especially for advanced patients.
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http://dx.doi.org/10.1186/s12882-021-02453-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244187PMC
June 2021

Male sex is associated with worse microbiological and clinical outcomes following tuberculosis treatment: A retrospective cohort study, a systematic review of the literature, and meta-analysis.

Clin Infect Dis 2021 Jun 8. Epub 2021 Jun 8.

Division of Infectious Diseases, Department of Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA.

Background: Although the incidence of tuberculosis (TB) is higher in males compared to females, the relationship of sex with TB treatment outcomes has not been adequately studied.

Methods: We performed a retrospective cohort study and a systematic review and meta-analysis of observational studies during the last 10 years to assess sex differences in clinical and microbiological outcomes in tuberculosis.

Results: In our cohort of 2,894 patients with drug-susceptible pulmonary TB (1,975 males and 919 females), males had higher adjusted hazards of 9-month mortality due to all causes (HR 1·43,95%CI 1.03-1.98) and infections (HR 1.70, 95%CI 1.09-2.64) and higher adjusted odds ratio for 2-month sputum culture positivity (OR 1.56,95%CI 1.05-2.33) compared to females. Smear positivity at 2 months was not significantly different (OR 1.27, 0.71-2.27) between the sexes. Among 7,896 articles retrieved, 398 articles were included in our systematic review describing a total of 3,957,216 patients. The odds of all-cause mortality were higher in males compared to females in the pooled unadjusted (OR 1.26, 95%CI 1.19-1.34) and adjusted (OR 1.31, 95%CI 1.18-1.45) analyses. Males had higher pooled odds of sputum culture (OR 1.44,95% CI 1.14-1.81) and sputum smear (OR 1.58,95%CI 1.41-1.77) positivity, both at the end of the intensive phase and upon treatment completion.

Conclusions: Our retrospective cohort showed that male TB patients have higher 9-month all-cause and infection-related mortality, with higher 2-month sputum culture positivity after adjusting for confounding factors. In our meta-analysis, males showed higher all-cause and TB-related mortality and higher sputum culture and smear positivity rates during and after TB treatment.
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http://dx.doi.org/10.1093/cid/ciab527DOI Listing
June 2021

Proteomic Analysis of the Responses to Co-Stimulation of Intestinal Aeromonas and Shewanella in Lamprey Leukocytes.

Curr Microbiol 2021 Jul 15;78(7):2631-2639. Epub 2021 May 15.

School of Life Science, Liaoning Normal University, Dalian, China.

Lamprey, one of the most basal jawless vertebrate, is an excellent model for studying vertebrate evolution, embryo development, and the origin of adaptive immunity. This study investigated the differentially expressed proteins in lamprey leukocytes in response to the co-stimulation of intestinal Aeromonas and Shewanella by using quantitative proteomics techniques. Significant differentially expressed proteins were identified. Gene Ontology annotation and the Kyoto Encyclopedia of Genes and Genomes pathway based on the significant differentially expressed proteins were analyzed. Most of the differentially expressed proteins were predicted to be involved in important signaling pathways. Quantitative real-time polymerase chain reaction was used to verify the expression of differentially expressed proteins at the mRNA level. The expression of some differentially expressed proteins was not consistent at the mRNA and protein levels. Differentially expressed proteins that are essential for lamprey-intestinal bacteria interaction should be identified to understand the lamprey adaptive immune response induced by gut microbiota.
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http://dx.doi.org/10.1007/s00284-021-02530-9DOI Listing
July 2021

Role of the IL-33/ST2 receptor axis in ovarian cancer progression.

Oncol Lett 2021 Jul 29;22(1):504. Epub 2021 Apr 29.

Department of Gynecological Oncology, The First Hospital of Jilin University, Changchun, Jilin 130061, P.R. China.

Ovarian cancer remains a significant health problem for women in the world due to its diagnosis at advanced stages of disease and the high mortality rate of patients. To date, ovarian cancer is frequently treated with tumor reduction surgery followed by platinum/paclitaxel-based chemotherapy; however, most patients eventually develop relapsed disease. The mRNA expression levels of interleukin-33 (IL-33) and the suppressor of tumorigenicity 2 (ST2) receptor are significantly upregulated in ovarian cancer tissues and metastatic tumor lesions. In addition, IL-33 and ST2 expression has been associated with a poor overall survival in patients with epithelial ovarian cancer. The IL-33 receptor ST2 is expressed as both a membrane-anchored receptor (ST2L) activated by IL-33, and as a soluble variant that exhibits anti-inflammatory properties. In the present review, the functions of the IL-33/ST2L axis in cells and their aberrant expression levels in ovarian cancer were discussed. In addition, targeting their expression as a novel strategy for the control of ovarian cancer progression was emphasized.
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http://dx.doi.org/10.3892/ol.2021.12765DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8114463PMC
July 2021

Biomimetic oligopeptide formed enamel-like tissue and dentin tubule occlusion via mineralization for dentin hypersensitivity treatment.

J Appl Biomater Funct Mater 2021 Jan-Dec;19:22808000211005384

Department of Periodontology, Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, China.

Objective: Dentin hypersensitivity (DH) is a common oral disease with approximately 41.9% prevalence. Reconstruction of dental hard tissues is the preferred treatment for relieving DH. Here, we applied biomineralization method using oligopeptide simulating cementum protein 1 (CEMP1) to regenerate hard tissues on demineralized dentin.

Methods: The self-assembly and biomineralization property of the oligopeptide were detected by scanning electron microscopy (SEM), circular dichroism spectroscopy, and transmission electron microscopy. Oligopeptide's binding capacity to demineralized dentin was evaluated by SEM and attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR). Remineralization was characterized using SEM, ATR-FTIR, X-ray diffraction, and nanoindentation. Oligopeptide's biocompatibility was evaluated using periodontal ligament cells.

Results: Oligopeptides self-assembled into nano-matrix and templated mineral precursor formation within 24 h. Moreover, oligopeptide nano-matrix bound firmly on demineralized dentin and resisted water rinsing. Then, bound nano-matrix served as a template to initiate nucleation and transformation of hydroxyapatite on demineralized dentin. After 96 h, oligopeptide nano-matrix regenerated an enamel-like tissue layer with a thickness of 15.35 μm, and regenerated crystals occluded dentin tubules with a depth of 31.27 μm. Furthermore, the oligopeptide nano-matrix had good biocompatibility when co-cultured with periodontal ligament cells.

Conclusions: This biomimetic oligopeptide simulating CEMP1 effectively induced remineralization and reconstructed hard tissues on demineralized dentin, providing a potential biomaterial for DH treatment.
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http://dx.doi.org/10.1177/22808000211005384DOI Listing
March 2021

BACH1 recruits NANOG and histone H3 lysine 4 methyltransferase MLL/SET1 complexes to regulate enhancer-promoter activity and maintains pluripotency.

Nucleic Acids Res 2021 02;49(4):1972-1986

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Shanghai Key Laboratory of Bioactive Small Molecules; Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China.

Maintenance of stem-cell identity requires proper regulation of enhancer activity. Both transcription factors OCT4/SOX2/NANOG and histone methyltransferase complexes MLL/SET1 were shown to regulate enhancer activity, but how they are regulated in embryonic stem cells (ESCs) remains further studies. Here, we report a transcription factor BACH1, which directly interacts with OCT4/SOX2/NANOG (OSN) and MLL/SET1 methyltransferase complexes and maintains pluripotency in mouse ESCs (mESCs). BTB domain and bZIP domain of BACH1 are required for these interactions and pluripotency maintenance. Loss of BACH1 reduced the interaction between NANOG and MLL1/SET1 complexes, and decreased their occupancy on chromatin, and further decreased H3 lysine 4 trimethylation (H3K4me3) level on gene promoters and (super-) enhancers, leading to decreased enhancer activity and transcription activity, especially on stemness-related genes. Moreover, BACH1 recruited NANOG through chromatin looping and regulated remote NANOG binding, fine-tuning enhancer-promoter activity and gene expression. Collectively, these observations suggest that BACH1 maintains pluripotency in ESCs by recruiting NANOG and MLL/SET1 complexes to chromatin and maintaining the trimethylated state of H3K4 and enhancer-promoter activity, especially on stemness-related genes.
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http://dx.doi.org/10.1093/nar/gkab034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7913776PMC
February 2021

Comparison of kinesio taping and sham taping in patients with chronic low back pain: A protocol of randomized controlled trial.

Medicine (Baltimore) 2020 Nov;99(47):e23042

Department of Orthopedics, Second Affiliated Hospital of Suzhou University, China.

Background: Chronic low back pain (CLBP) is a clinical condition characterized by moderate to severe pain in the lower spine that severely affects the patient's life experience and leads to disability and absenteeism. In the past few years, kinesio tape (KT) have been utilized by physiotherapists as a relatively novel band-aid method to reduce the pain of musculoskeletal disorders. Therefore, in this particular study, we intended to search the effects of KT and sham KT on pain, lumbar range of motion, and disability for CLBP.

Methods: The present study was experimented in a physiotherapy clinic in the Yancheng First People's Hospital of Jiangsu Province. The study design was a randomized, double-blinded clinical trial. Inclusion criteria for the study were the followings: chief complaint pain in the area between 12 ribs and hip creases with or without leg pain; ages ranges from 18 to 65; low back pain lasts <6 weeks; and at any rate medium pain intensity (pain score ≥4). Participants were randomly allocated to 1 of 2 parallel combinations to receive either therapeutic KT or sham KT. Patients were assessed at baseline, at the end of the 12-day intervention, and at 4 weeks of follow-up. The main result measure was pain intensity using a numerical rating scale (NRS), and the secondary outcome measure was lumbar lateral flexion activity, Oswestry Disability Index (ODI), and adverse effects including allergic reactions or skin problems.

Conclusions: The results of this study will provide new information about the usefulness of KT as an additional component of a guideline-endorsed physiotherapy program in patients with chronic nonspecific low back pain.

Trial Registration: This study protocol was registered in Research Registry (researchregistry6070).
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http://dx.doi.org/10.1097/MD.0000000000023042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676582PMC
November 2020

Determination of Environmental Micro(Nano)Plastics by Matrix-Assisted Laser Desorption/Ionization-Time-of-Flight Mass Spectrometry.

Anal Chem 2020 11 17;92(21):14346-14356. Epub 2020 Sep 17.

State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong SAR 999077, P. R. China.

Micro(nano)plastics (MNPs) are widely acknowledged as global environmental threat while determination methods for MNPs are still lacking and becoming a growing concern. This study provides a novel method for MNPs identification/quantification by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS). Factors affecting the measurement were optimized, including laser energy, matrix (M), analyte (A), cationization agent (C), and MAC volume ratio. Under the optimal conditions, the peaks representative of polystyrene (PS) and polyethylene terephthalate (PET) were identified, and the mass differences were consistent with the molecular weight of the corresponding oligomer. A quantitative correlation was built between normalized signal intensity and ln[polymer concentration] with a correlation coefficient above 0.96 for low-molecular-weight polymers and 0.98 for high-molecular-weight polymers. Furthermore, two types of environmental MNP samples were prepared, including aviation cup particles as fresh plastics and aged MNPs extracted from river sediment. By using MALDI-TOF MS, the PS-related MNPs (in both aviation cup and sediment) consisted of CH and CHO oligomers, while the PET-related MNPs (only found in sediment) were identified with repeated units of CHO and CHO. According to the quantitative correlation curve, the contents of PS and PET MNPs were quantified as 8.56 ± 0.04 and 28.71 ± 0.20 mg·kg, respectively, in the collected sediment. This study is the first attempt to propose a quantification method with the employment of MALDI-TOF MS for aged MNPs analysis in environmental samples, which can not only supply an effective method for MNP analysis but also inspire future studies on the in situ distribution and transformation of MNPs in environmental and biological samples.
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http://dx.doi.org/10.1021/acs.analchem.0c01928DOI Listing
November 2020

TNF-a Is a Potent Stimulator of Tc9-Cell Differentiation.

J Immunother 2020 Nov/Dec;43(9):265-272

Cancer Immunology.

Tumor-specific Tc9 cells exhibit an excellent antitumor potential in tumor immunotherapy. Identification of factors that contribute to Tc9-cell differentiation may have important clinical significance. In this study, we found that tumor necrosis factor (TNF)-α promotes Tc9 differentiation in vitro, and the TNF-α-induced Tc9 cells display enhanced cell survival and cell proliferation. More importantly, the TNF-α-induced tumor-specific Tc9 cells have increased antitumor capabilities in vivo. TNF-α activates its downstream signaling through 2 cell surface receptors, TNFR1 and TNFR2. In this study, we found that TNF-α promotes Tc9-cell differentiation through TNFR2, but not TNFR1. Furthermore, we found that TNF-α-TNFR2 activates STAT5 and nuclear factor-κB signaling during Tc9-cell differentiation. Blocking STAT5 or nuclear factor-κB by their specific inhibitors partially abrogates TNF-α-induced promotion of Tc9-cell differentiation. Thus, our study demonstrated TNF-α as a potent stimulator of Tc9-cell differentiation and may have important clinical implications.
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http://dx.doi.org/10.1097/CJI.0000000000000335DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664956PMC
September 2021

Human-IgG-Neutralizing Monoclonal Antibodies Block the SARS-CoV-2 Infection.

Cell Rep 2020 07 3;32(3):107918. Epub 2020 Jul 3.

Shanghai Key Laboratory of Medical Epigenetics, International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences, Fudan University, and Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China. Electronic address:

Coronavirus disease 2019 (COVID-19) has become a worldwide threat to humans, and neutralizing antibodies have therapeutic potential. We have purified more than 1,000 memory B cells specific to SARS-CoV-2 S1 or its RBD (receptor binding domain) and obtain 729 paired heavy- and light-chain fragments. Among these, 178 antibodies test positive for antigen binding, and the majority of the top 17 binders with EC below 1 nM are RBD binders. Furthermore, we identify 11 neutralizing antibodies, eight of which show IC within 10 nM, and the best one, 414-1, with IC of 1.75 nM. Through epitope mapping, we find three main epitopes in RBD recognized by these antibodies, and epitope-B antibody 553-15 could substantially enhance the neutralizing abilities of most of the other antibodies. We also find that 515-5 could cross neutralize the SARS-CoV pseudovirus. Altogether, our study provides 11 potent human neutralizing antibodies for COVID-19 as therapeutic candidates.
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http://dx.doi.org/10.1016/j.celrep.2020.107918DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7332464PMC
July 2020

Therapeutic effect of percutaneous vertebroplasty and nonoperative treatment on osteoporotic vertebral compression fracture: A randomized controlled trial protocol.

Medicine (Baltimore) 2020 Jul;99(27):e20770

Department of Spinal Surgery, Yancheng NO.1 People's Hospital, Jiang Su, China.

Background: Osteoporosis and related complications have been increasing with the aging population. Osteoporotic vertebral compression fractures (OVCFs) are the most common among all osteoporotic fractures. The purpose of this study was performed to compare the efficiency and safety of vertebroplasty versus conservative treatment for acute OVCFs.

Methods: The conduct of this study followed the Declaration of Helsinki principles and the reporting of this study adhered to the Consolidated Standards of Reporting Trials guidelines for randomized controlled trials. Written informed consent was obtained from every participant. Participants were randomly assigned (1:1) to receive either vertebroplasty or control group. The primary outcome was pain relief at 1 month and 1 year, measured with a Visual Analogue Scale score. The secondary outcomes were Roland-Morris Disability Questionnaire, short form score, European Quality of Life-5 Dimensions, and postoperative complications.

Results: We hypothesize that vertebroplasty will provide a rapid decrease of pain and an early return to daily life activities compared with the control group.

Trial Registration: This study protocol was registered in Research Registry (researchregistry5624).
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http://dx.doi.org/10.1097/MD.0000000000020770DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7337563PMC
July 2020

Refined spatial temporal epigenomic profiling reveals intrinsic connection between PRDM9-mediated H3K4me3 and the fate of double-stranded breaks.

Cell Res 2020 03 11;30(3):256-268. Epub 2020 Feb 11.

State Key Laboratory of Molecular Biology, Shanghai Key Laboratory of Molecular Andrology, CAS Center for Excellence in Molecular Cell Science, Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, 200031, China.

Meiotic recombination is initiated by the formation of double-strand breaks (DSBs), which are repaired as either crossovers (COs) or noncrossovers (NCOs). In most mammals, PRDM9-mediated H3K4me3 controls the nonrandom distribution of DSBs; however, both the timing and mechanism of DSB fate control remain largely undetermined. Here, we generated comprehensive epigenomic profiles of synchronized mouse spermatogenic cells during meiotic prophase I, revealing spatiotemporal and functional relationships between epigenetic factors and meiotic recombination. We find that PRDM9-mediated H3K4me3 at DSB hotspots, coinciding with H3K27ac and H3K36me3, is intimately connected with the fate of the DSB. Our data suggest that the fate decision is likely made at the time of DSB formation: earlier formed DSBs occupy more open chromatins and are much more competent to proceed to a CO fate. Our work highlights an intrinsic connection between PRDM9-mediated H3K4me3 and the fate decision of DSBs, and provides new insight into the control of CO homeostasis.
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http://dx.doi.org/10.1038/s41422-020-0281-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7054334PMC
March 2020

Spatial-temporal distribution of microplastics in surface water and sediments of Maozhou River within Guangdong-Hong Kong-Macao Greater Bay Area.

Sci Total Environ 2020 May 22;717:135187. Epub 2019 Nov 22.

State Key Laboratory of Environmental and Biological Analysis, Department of Chemistry, Hong Kong Baptist University, Hong Kong Special Administrative Region. Electronic address:

Concerns over the negative impacts of microplastics on human health have led to growing attention on the occurrence of microplastics in aquatic environment. Recent studies have extended their focus from marine to inland waters, especially on the spatial-temporal distribution of the microplastics in urban rivers. In this study, Maozhou River, the largest river in Shenzhen, a tributary of the Pearl River, was selected as a representative inland waterway of Guangdong-Hong Kong-Macao Greater Bay Area. The spatial-temporal investigation was performed on microplastics in the surface water and sediments of 17 sites along the mainstream of the Maozhou River. Results show that microplastics were widely and unevenly distributed along the river and reached the high abundances on the site most intensively surrounded by industries as well as the sites downstream. The abundances in dry season ranged from 4.0 ± 1.0 to 25.5 ± 3.5 items·L in water and 35 ± 15 to 560 ± 70 item·kg in sediments, which were relatively higher than those observed in the wet season (water: 3.5 ± 1.0 to 10.5 ± 2.5 items·L; sediments: 25 ± 5 to 360 ± 90 item·kg; p value < 0.05). The dominant types of the microplastics were identified as: PE Polyethylene (PE, water: 45.0%, sediments: 42.0%), polypropylene (PP, water and sediments: 12.5%), polystyrene (PS, water: 34.5%; sediments 14.5%) and polyvinyl chloride (PVC, water: 2.0%; sediments: 15%). Moreover, metals like Al, Si, Ca were discovered on the rough surface of the microplastics, indicating the interactions between the microplastics and the aquatic environment. Through a comprehensive comparison with other major inland waters in China, this work provides valuable data on the microplastics pollution of a representative inland water in the Greater Bay Area, and will further contribute to a better understanding on the land-based input of microplastics from the intensively affected inland waters.
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http://dx.doi.org/10.1016/j.scitotenv.2019.135187DOI Listing
May 2020

HNF1B-mediated repression of SLUG is suppressed by EZH2 in aggressive prostate cancer.

Oncogene 2020 02 21;39(6):1335-1346. Epub 2019 Oct 21.

Key Laboratory of Epigenetics and Metabolism, Ministry of Science and Technology, Institutes of Biomedical Sciences; Key Laboratory of Carcinogenesis and Cancer Invasion, Ministry of Education, Liver Cancer Institute, Zhongshan Hospital, Fudan University, 200032, Shanghai, China.

Prostate cancer is the most common malignancy in men in developed countries. Overexpression of enhancer of zeste homolog 2 (EZH2), the major histone H3 lysine 27 methyltransferase, has been connected to prostate cancer malignancy. However, its downstream genes and pathways have not been well established. Here, we show tumor suppressor Hepatocyte Nuclear Factor 1β (HNF1B) as a direct downstream target of EZH2. EZH2 binds HNF1B locus and suppresses HNF1B expression in prostate cancer cell lines, which is further supported by the reverse correlation between EZH2 and HNF1B expression in clinical samples. Consistently, restored HNF1B expression significantly suppresses EZH2-mediated overgrowth and EMT processes, including migration and invasion of prostate cancer cell lines. Mechanistically, we find that HNF1B primarily binds the promoters of thousands of target genes, and differentially regulates the expression of 876 genes. We also identify RBBP7/RbAP46 as a HNF1B interacting protein which is required for HNF1B-mediated repression of SLUG expression and EMT process. Importantly, we find that higher HNF1B expression strongly predicts better prognosis of prostate cancer, alone or together with lower EZH2 expression. Taken together, we have established a previously underappreciated axis of EZH2-HNF1B-SLUG in prostate cancer, and also provide evidence supporting HNF1B as a potential prognosis marker for metastatic prostate cancer.
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http://dx.doi.org/10.1038/s41388-019-1065-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002300PMC
February 2020

Application Of Adoptive Immunotherapy In Ovarian Cancer.

Onco Targets Ther 2019 27;12:7975-7991. Epub 2019 Sep 27.

Department of Cancer Immunology, The First Hospital of Jilin University, Changchun 130061, China.

Ovarian cancer (OC) has been the most fatal gynecological disease that threatens women's health. Surgery and platinum-based chemotherapy are the basic ovarian cancer treatments that can improve survival, but the five-year survival rate has not improved because of delayed diagnosis, drug resistance, and recurrence. Novel treatments are needed to improve the prognosis and survival rate of ovarian cancer patients. In recent years, adoptive cell therapy (ACT) has received increasing attention as an emerging therapeutic strategy in the treatment of solid tumors including OC. ACT has shown promising results in many preclinical and clinical trials of OC. The application of ACT depends on different effector cells, such as lymphokine-activated killer (LAK) cells, tumor-infiltrating lymphocytes (TILs), and genetically modified T cells. In this review, we focus on adoptive immunotherapies in ovarian cancer and summarize completed and ongoing preclinical/clinical trials. The future development directions and obstacles for ACT in OC treatment are discussed.
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http://dx.doi.org/10.2147/OTT.S221773DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6775498PMC
September 2019

Soft, Skin-Interfaced Microfluidic Systems with Passive Galvanic Stopwatches for Precise Chronometric Sampling of Sweat.

Adv Mater 2019 Aug 17;31(32):e1902109. Epub 2019 Jun 17.

Department of Materials Science and Engineering, Northwestern University, Evanston, IL, 60208, USA.

Comprehensive analysis of sweat chemistry provides noninvasive health monitoring capabilities that complement established biophysical measurements such as heart rate, blood oxygenation, and body temperature. Recent developments in skin-integrated soft microfluidic systems address many challenges associated with standard technologies in sweat collection and analysis. However, recording of time-dependent variations in sweat composition requires bulky electronic systems and power sources, thereby constraining form factor, cost, and modes of use. Here, presented are unconventional design concepts, materials, and device operation principles that address this challenge. Flexible galvanic cells embedded within skin-interfaced microfluidics with passive valves serve as sweat-activated "stopwatches" that record temporal information associated with collection of discrete microliter volumes of sweat. The result allows for precise measurements of dynamic sweat composition fluctuations using in situ or ex situ analytical techniques. Integrated electronics based on near-field communication (NFC) protocols or docking stations equipped with standard electronic measurement tools provide means for extracting digital timing results from the stopwatches. Human subject studies of time-stamped sweat samples by in situ colorimetric methods and ex situ techniques based on inductively coupled plasma mass spectroscopy (ICP-MS) and chlorodimetry illustrate the ability to quantitatively capture time-dynamic sweat chemistry in scenarios compatible with field use.
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http://dx.doi.org/10.1002/adma.201902109DOI Listing
August 2019

TNF-α enhances Th9 cell differentiation and antitumor immunity via TNFR2-dependent pathways.

J Immunother Cancer 2019 02 4;7(1):28. Epub 2019 Feb 4.

Department of Cancer Immunology, The First Hospital of Jilin University, 519 Dongminzhu St, ChangChun, Jilin, China.

Tumor specific Th9 cells are potential effector cells for adoptive therapy of human cancers. TNF family members OX40L, TL1A and GITRL have been shown to promote the induction of Th9 cells and antitumor immunity. However, the role of TNF-α, the prototype of the TNF superfamily cytokines, in Th9 cell differentiation and their antitumor efficacy is not defined. Here, we showed that TNF-α potently promoted naïve CD4 T cells to differentiate into Th9 cells in vitro. Furthermore, the addition of TNF-α during Th9 cell differentiation increased T cell survival and proliferation. More importantly, the adoptive transfer of TNF-α-treated Th9 cells induced more potent antitumor effects than regular Th9 cells in mouse tumor model. TNF-α signals via two cell surface receptors, TNFR1 and TNFR2. Mechanistic studies revealed that TNF-α drove Th9 cell differentiation through TNFR2 but not TNFR1. In addition, under Th9 polarizing condition, TNF-α activated STAT5 and NF-κB pathways in T cells in a TNFR2-dependent manner. Inhibition of STAT5 and NF-κB pathways by their specific inhibitors impaired TNF-α-induced Th9 cell differentiation. Our results identified TNF-α as a new powerful inducer of Th9 cells and clarified the molecular mechanisms underlying TNF-α-induced Th9 cell differentiation.
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http://dx.doi.org/10.1186/s40425-018-0494-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360681PMC
February 2019

Comparative transcriptomics identifies patterns of selection in roses.

BMC Plant Biol 2018 Dec 22;18(1):371. Epub 2018 Dec 22.

Group of Plant Molecular Genetics and Adaptation, CAS Key Laboratory for Plant Diversity and Biogeography of East Asia, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, 650201, China.

Background: Roses are important plants for human beings with pivotal economical and biological traits like continuous flowering, flower architecture, color and scent. Due to frequent hybridization and high genome heterozygosity, classification of roses and their relatives remains a big challenge.

Results: Here, to identify potential markers for phylogenetic reconstruction and to reveal the patterns of natural selection in roses, we generated sets of high quality and comprehensive reference transcriptomes for Rosa chinensis 'Old Blush' (OB) and R. wichuriana 'Basye's Thornless' (BT), two species exhibiting contrasted traits of high economical importance. The assembled reference transcriptomes showed transcripts N50 above 2000 bp. Two roses shared about 10,073 transcripts (N50 = 2282 bp), in which a set of 5959 transcripts was conserved within genera of Rosa. Further comparison with species in Rosaceae identified 4447 transcripts being common (Rosaceae-common) in Rosa, Malus, Prunus, Rubus, and Fragaria, while a pool of 164 transcripts being specific for roses (Rosa-specific). Among the Rosaceae-common transcripts, 409 transcripts showed a signature of positive selection and a clustered expression in different tissues. Interestingly, nine of these rapidly evolving genes were related to DNA damage repair and responses to environmental stimulus, a potential associated with genome confliction post hybridization. Coincident with this fast evolution pattern in rose genes, 24 F-box and four TMV resistant proteins were significantly enriched in the Rosa-specific genes.

Conclusions: We expect that these Rosaceae-common and Rosa-specific transcripts should facilitate the phylogenetic analysis of Rosaceae plants as well as investigations of Rosa-specific biology. The data reported here could provide fundamental genomic tools and knowledge critical for understanding the biology and domestication of roses and for roses breeding.
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http://dx.doi.org/10.1186/s12870-018-1585-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6303930PMC
December 2018

IL-33 drives the antitumor effects of dendritic cells via the induction of Tc9 cells.

Cell Mol Immunol 2019 07 1;16(7):644-651. Epub 2018 Oct 1.

Department of Cancer Immunology, The First Hospital of Jilin University, Changchun, 130061, China.

Dendritic cell (DC) tumor vaccines exert their antitumor effects through the induction of effector T cells. We recently identified Tc9 cells as a new potent antitumor effector T cell subset. However, approaches to direct DCs to preferably prime antitumor Tc9 cells should be further exploited. Here, we demonstrate that the addition of interleukin (IL)-33 potently promotes the induction of Tc9 cells by DCs in vitro and in vivo. IL-33 treatment also drives the cytotoxic activities of DC-induced Tc9 cells. Notably, IL-33 treatment enhances cell survival and proliferation of DC-primed CD8 T cells. More importantly, the addition of IL-33 during in vitro priming of tumor-specific Tc9 cells by DCs increases the antitumor capability of Tc9 cells. Mechanistic studies demonstrated that IL-33 treatment inhibits exhaustive CD8 T cell differentiation by inhibiting PD-1 and 2B4 expression and increasing IL-2 and CD127 (IL-7 receptor-α, IL-7Rα) expression in CD8 T cells. Finally, the addition of IL-33 further promotes the therapeutic efficacy of DC-based tumor vaccines in the OT-I mouse model. Our study demonstrates the important role of IL-33 in DC-induced Tc9 cell differentiation and antitumor immunity and may have important clinical implications.
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http://dx.doi.org/10.1038/s41423-018-0166-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6804534PMC
July 2019

Interleukin-33 Contributes to the Induction of Th9 Cells and Antitumor Efficacy by Dectin-1-Activated Dendritic Cells.

Front Immunol 2018 31;9:1787. Epub 2018 Jul 31.

Department of Cancer Immunology, The First Hospital of Jilin University, Changchun, China.

We recently discovered that dectin-1-activated dendritic cells (DCs) drive potent T helper (Th) 9 cell responses and antitumor immunity. However, the underlying mechanisms need to be further defined. The cytokine microenvironment is critical for Th cell differentiation. Here, we show that dectin-1 activation enhances interleukin (IL)-33 expression in DCs. We found that blocking IL-33/ST2 inhibits dectin-1-activated DC-induced Th9 cell differentiation. More importantly, the addition of IL-33 further promotes Th9 cell priming and antitumor efficacy induced by dectin-1-activated DCs. Mechanistically, in addition to the promotion of Th9 and Th1 cells, dectin-1-activated DCs combined with IL-33 abolish the activity of IL-33 in the induction of regulatory T cells. Furthermore, the combined treatment of dectin-1-activated DCs and IL-33 increases the frequencies of CD4 T cells by fostering their proliferation and inhibiting their exhaustive differentiation. Thus, our results demonstrate the important role of IL-33 in dectin-1-activated DC-induced Th9 cell differentiation and antitumor efficacy, and suggest that the combination of dectin-1-activated DCs and IL-33 may present a new effective modality of DC-based vaccines in tumor immunotherapy.
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http://dx.doi.org/10.3389/fimmu.2018.01787DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6079242PMC
September 2019

The effect of ozone on hypoxia, hemolysis and morphological change of blood from patients with aortic dissection (AD): a preliminary experiment of ozonated autohemotherapy for treating AD.

Am J Transl Res 2018 15;10(6):1829-1840. Epub 2018 Jun 15.

Department of Cardiovascular Surgery, The First Affiliated Hospital of Harbin Medical University Harbin, China.

This study aimed to investigate the effect of ozone on hypoxia, hemolysis and morphological change of blood from aortic dissection (AD) patients for providing preliminary evidence of application of ozonated autohemotherapy (Ozone-AHT) in AD patients. 20 AD patients and 20 healthy volunteers were consecutively included, and blood samples were collected from all participants and ozonized . PO, SO, malondialdehyde (MDA), superoxide dismutase (SOD), malformation percentage, morphology change and spatial distribution of filamentous actin (F-actin) in erythrocytes at different ozone concentrations were evaluated. After ozonation of whole blood, the median levels of PO and SO increased under Ozone concentrations at 40 μg/mL, 80 μg/mL and 160 μg/mL compared with samples exposed to 0 μg/mL in both AD group and control group. The MDA level was similar in samples exposed to 0 μg/mL, 40 μg/mL and 80 μg/mL ozone, while the levels of SOD increased in samples exposed to 40 μg/mL and 80 μg/mL in both AD group and control group. Compared with the samples exposed to 0 μg/mL ozone, FHb level only increased in samples exposed to 80 μg/mL and 160 μg/mL Ozone in both AD group and control group. In addition, overdosed ozone (160 μg/mL) but not therapeutic ozone concentrations (0 μg/mL, 40 μg/mL and 80 μg/mL) increased malformation percentage and morphology change of erythrocytes in both AD group and control group. In conclusion, Ozone improves oxygen content and reduces oxidative damage in blood from AD patients, and therapeutic dose ozone do not induce hemolysis and morphology change of erythrocytes.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6038082PMC
June 2018

Dectin-1 stimulates IL-33 expression in dendritic cells via upregulation of IRF4.

Lab Invest 2018 06 14;98(6):708-714. Epub 2018 Mar 14.

Department of Cancer Immunology, The First Hospital of Jilin University, Changchun, 130061, China.

Interleukin-33 (IL-33) is a potent contributor to antiviral immune responses and antitumor immunity. We recently discovered that IL-33 is overexpressed in dectin-1-activated dendritic cells (DCs). However, mechanisms of dectin-1-induced IL-33 expression in DCs remain elusive. Curdlan, an agonist of dectin-1, was used to mature DCs in this study. We found that dectin-1-induced IL-33 expression in DCs relies on Syk and Raf-1 pathways. By using nuclear factor (NF)-κB inhibitors, we also found that dectin-1-induced IL-33 expression relies on NF-κB signaling. Furthermore, through Syk/Raf-1-NF-κB pathway, dectin-1 signaling stimulates DCs to overexpress interferon regulatory factor 4 (IRF4), which directly upregulates the expression of IL-33 in dectin-1-activated DCs. Thus, our study provides new insights into the mechanisms of dectin-1-induced IL-33 expression in DCs and may provide new targets for improving DC-based cancer immunotherapy.
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http://dx.doi.org/10.1038/s41374-018-0047-2DOI Listing
June 2018

LanCL1 protects prostate cancer cells from oxidative stress via suppression of JNK pathway.

Cell Death Dis 2018 02 7;9(2):197. Epub 2018 Feb 7.

Department of Urology, Huashan Hospital, Fudan University, Shanghai, China.

Prostate cancer (PCa) is the most commonly diagnosed malignancy in male. Numerous studies have focused on the molecular mechanisms of carcinogenesis and progression, aiming at developing new therapeutic strategies. Here we describe Lanthionine synthase C-like protein 1 (LanCL1), a member of the LanCL family, is a potential prostate cancer susceptibility gene. LanCL1 promotes prostate cancer cell proliferation and helps protect cells from damage caused by oxidative stress. Suppression of LanCL1 by siRNA results in increased cancer cell apoptosis. Clinical data also indicate that LanCL1 upregulation in human prostate cancers correlates with tumor progression. Finally, we demonstrate that LanCL1 plays such important role through inhibiting JNK pathway. Altogether, our results suggest that LanCL1 protects cells from oxidative stress, and promotes cell proliferation. LanCL1 reduces cell death via suppression of JNK signaling pathway.
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http://dx.doi.org/10.1038/s41419-017-0207-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5833716PMC
February 2018

Identification of the histone lysine demethylase KDM4A/JMJD2A as a novel epigenetic target in M1 macrophage polarization induced by oxidized LDL.

Oncotarget 2017 Dec 10;8(70):114442-114456. Epub 2017 May 10.

Department of Neurology, the First Hospital of Jilin University, Changchun, Jilin, China.

Oxidized low density lipoprotein (oxLDL) induces macrophage activation, an event essential for atherosclerosis. Emerging evidence supports that epigenetic regulation plays important roles in macrophage activation and function. However, it remains unclear which epigenetic modulator is responsible for oxLDL-induced macrophage activation. Here, we identify for the first time KDM4A (JMJD2A) as an epigenetic modifying enzyme that controls oxLDL-induced pro-inflammatory M1 polarization of macrophages. OxLDL triggered M1 polarization of murine and human macrophages, characterized by expression of iNOS and robust production of inflammatory cytokines (e.g., TNF-α, MCP-1, IL-1β). In contrast, protein level of the M2 marker Arg1 was clearly decreased after treated with oxLDL. Notably, exposure to oxLDL resulted in markedly increased expression of KDM4A in macrophages. Functionally, shRNA knockdown of KDM4A significantly impaired M1 polarization and expression of inflammatory cytokines induced by oxLDL, accompanied by increased expression of Arg1 and VEGF. However, inhibition of KDM4A by shRNA or the pan-selective KDM inhibitor JIB-04 did not affect oxLDL-mediated activation of the NF-κB and hypoxia inducible factor (HIF) pathways, and vice versa. In addition, JIB-04 induced apoptosis of macrophages in a dose-dependent manner, an event attenuated by oxLDL. Together, these findings argue that KDM4A might represent a novel epigenetic modulator that acts to direct oxLDL-induced M1 polarization of macrophages, while its up-regulation is independent of NF-κB and HIF activation, two signals critical for pro-inflammatory activation of macrophages. They also suggest that KDM4A might serve as a potential target for epigenetic therapy in prevention and treatment of inflammatory diseases such as atherosclerosis.
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http://dx.doi.org/10.18632/oncotarget.17748DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5777704PMC
December 2017
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