Publications by authors named "Xiaohui Su"

67 Publications

IL-13 Derived Type 2 Innate Lymphocytes Ameliorates Cardiomyocyte Apoptosis Through STAT3 Signaling Pathway.

Front Cell Dev Biol 2021 20;9:742662. Epub 2021 Sep 20.

Department of Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai, China.

The involvement of cardiomyopathy during sepsis means higher mortality and prolonged length of hospital stay. Many efforts have been made to alleviate the apoptosis of cardiomyocytes in sepsis. The huge potential of IL-13 in tissue repair has attracted increasing attention. In the present study, we used LPS-treated mice or primary cardiomyocytes as a sepsis model to explore the anti-apoptotic ability of IL-13. It was found that an increased level of exogenous IL-13 was beneficial to the recovery of heart function in sepsis, and this anti-apoptotic effect of IL-13 was probably through enhancing the phosphorylation of STAT3 Ser727. In addition, we identified that the heart protective effect of IL-13 was associated with type 2 innate lymphocytes (ILC2). All these findings may provide a potential promising treatment for sepsis-induced cardiomyopathy.
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http://dx.doi.org/10.3389/fcell.2021.742662DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488199PMC
September 2021

Comprehensive Analysis of Potential miRNA-Target mRNA-Immunocyte Subtype Network in Cerebral Infarction.

Eur Neurol 2021 Sep 20:1-14. Epub 2021 Sep 20.

Clinical Laboratory, Hebei Red Cross Boai Hospital, Shijiazhuang, China.

Introduction: Cerebral infarction (CI) is one of the leading causes of serious long-term disability and mortality.

Objective: We aimed to identify potential miRNAs and target mRNAs and assess the involvement of immunocyte infiltration in the process of CI.

Methods: First, miRNA and mRNA data were downloaded from the Gene Expression Omnibus database, followed by differential expression analysis. Second, correlation analysis between differentially expressed mRNAs and differential immunocyte subtypes was performed through the CIBERSORT algorithm. Third, the regulatory network between miRNAs and immunocyte subtype-related mRNAs was constructed followed by the functional analysis of these target mRNAs. Fourth, correlation validation between differentially expressed mRNAs and differential immunocyte subtypes was performed in the GSE37587 dataset. Finally, the diagnostic ability of immunocyte subtype-related mRNAs was tested.

Results: Up to 17 differentially expressed miRNAs and 3,267 differentially expressed mRNAs were identified, among which 310 differentially expressed mRNAs were significantly associated with immunocyte subtypes. Several miRNA-target mRNA-immunocyte subtype networks including hsa-miR-671-3p-ZC3HC1-neutrophils, hsa-miR-625-CD5-monocytes, hsa-miR-122-ACOX1/DUSP1/NEDD9-neutrophils, hsa-miR-455-5p-SLC24A4-monocytes, and hsa-miR-455-5p-SORL1-neutrophils were identified. LAT, ACOX1, DUSP1, NEDD9, ZC3HC1, BIN1, AKT1, DNMT1, SLC24A4, and SORL1 had a potential diagnostic value for CI.

Conclusions: The network including miRNA, target mRNA, and immunocyte subtype may be novel regulators and diagnostic and therapeutic targets in CI.
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http://dx.doi.org/10.1159/000518893DOI Listing
September 2021

Fengshi Qutong capsule ameliorates bone destruction of experimental rheumatoid arthritis by inhibiting osteoclastogenesis.

J Ethnopharmacol 2022 Jan 4;282:114602. Epub 2021 Sep 4.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, 100700, China. Electronic address:

Ethnopharmacological Relevance: Bone destruction plays a key role in damaging the joint function of rheumatoid arthritis (RA). Fengshi Qutong capsule (FSQTC) consisting of 19 traditional Chinese medicines has been used for treating RA in China for many years. Preliminary studies show that FSQTC has analgesic activity and inhibits synovial angiogenesis of collagen-induced arthritis (CIA), but its role on bone destruction of RA is still unclear.

Aim Of The Study: To explore the effect of FSQTC on bone destruction of RA and the possible mechanism of osteoclastogenesis in vivo and in vitro.

Materials And Methods: LC-MS system was used to detect the quality control components of FSQTC. The anti-arthritic effect of FSQTC on CIA rats was evaluated by arthritis score, arthritis incidence and histopathology evaluation of inflamed joints. The effect of treatment with FSQTC on bone destruction of joint tissues was determined with X-ray and micro-CT quantification, and on bone resorption marker CTX-I and formation marker osteocalcin in sera were detected by ELISA. Then, osteoclast differentiation and mature were evaluated by TRAP staining, actin ring immunofluorescence and bone resorption assay both in joints and RANKL-induced RAW264.7 cells. In addition, RANKL, OPG, IL-1β and TNFα in sera were evaluated by ELISA. The molecular mechanisms of the inhibitions were elucidated by analyzing the protein and gene expression of osteoclastic markers CTSK, MMP-9 and β3-Integrin, transcriptional factors c-Fos and NFATc1, as well as phosphorylation of ERK1/2, JNK and P38 in joints and in RANKL-induced RAW264.7 cells using western blot and/or qPCR.

Results: In this study, 12 major quality control components were identified. Our data showed that FSQTC significantly increased bone mineral density, volume fraction, trabecular thickness, and decreased trabecular separation of inflamed joints both at periarticular and extra-articular locations in CIA rats. FSQTC also diminished the level of CTX-I and simultaneously increased osteocalcin in sera of CIA rats. The effects were accompanied by reductions of osteoclast differentiation, bone resorption, and expression of osteoclastic markers (CTSK, MMP-9 and β3-Integrin) in joints. Interestingly, FSQTC treatment could reduce the protein level of RANKL, increase the expression of OPG, and decrease the ratio of RANKL to OPG in inflamed joints and sera of CIA rats. In addition, FSQTC inhibited the levels of pro-inflammatory cytokines implicated in bone resorption, such as IL-1β and TNFα in sera. When RAW264.7 cells were treated with RANKL, FSQTC inhibited the formation of TRAP + multinucleated cells, actin ring and the bone-resorbing activity in dose-dependent manners. Furthermore, FSQTC reduced the RANKL-induced expression of osteoclastic genes and proteins and transcriptional factors (c-Fos and NFATc1), as well as phosphorylation of mitogen-activated protein kinases (MAPKs).

Conclusion: FSQTC may inhibit bone destruction of RA by its anti-osteoclastogenic activity both in vivo and in vitro.
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http://dx.doi.org/10.1016/j.jep.2021.114602DOI Listing
January 2022

Evaluating Tumor-Infiltrating Lymphocytes in Breast Cancer Using Preoperative MRI-Based Radiomics.

J Magn Reson Imaging 2021 Aug 28. Epub 2021 Aug 28.

Breast Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, China.

Background: Evaluating tumor-infiltrating lymphocytes (TILs) in patients with breast cancer using radiomics has been rarely explored.

Purpose: To establish a radiomics nomogram based on dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) for preoperatively evaluating TIL level.

Study Type: Retrospective.

Population: A total of 154 patients with breast cancer were divided into a training cohort (N = 87) and a test cohort (N = 67), who were further divided into low TIL (<50%) and high TIL (≥50%) subgroups according to the histopathological results.

Field Strength/sequence: 3.0 T; axial T2-weighted imaging (fast spin echo), diffusion-weighted imaging (spin echo-echo planar imaging), and the volume imaging for breast assessment DCE sequence (gradient recalled echo).

Assessment: A radiomics signature was developed from the training dataset and independent risk factors were selected by multivariate logistic regression to build a clinical model. A nomogram model was built by combining radiomics score and risk factors. The performance of the nomogram was assessed using calibration curves and decision curves. The area under the receiver operating characteristic (ROC) curve, accuracy, sensitivity, and specificity were calculated.

Statistical Tests: The least absolute shrinkage and selection operator, univariate and multivariate logistic regression analysis, t-tests and chi-squared tests or Fisher's exact test, Hosmer-Lemeshow test, ROC analysis, and decision curve analysis were conducted. P < 0.05 was considered statistically significant.

Results: The radiomics signature and nomogram model exhibited better calibration and validation performance in the training (radiomics: area under the curve [AUC] 0.86; nomogram: AUC 0.88) and test (radiomics: AUC 0.83; nomogram: AUC 0.84) datasets compared with clinical model (training: AUC 0.76; test: AUC 0.72). The decision curve demonstrated that the nomogram model exhibited better performance than the clinical model, with a threshold probability between 0.15 and 0.9.

Data Conclusion: The nomogram model based on preoperative MRI exhibited an excellent ability for the noninvasive evaluation of TILs in breast cancer.

Level Of Evidence: 4 TECHNICAL EFFICACY STAGE: 2.
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http://dx.doi.org/10.1002/jmri.27910DOI Listing
August 2021

Microblog Topic-Words Detection Model for Earthquake Emergency Responses Based on Information Classification Hierarchy.

Int J Environ Res Public Health 2021 07 28;18(15). Epub 2021 Jul 28.

School of Information Science and Technology, Beijing Forestry University, Beijing 100083, China.

Social media data are constantly updated, numerous, and characteristically prominent. To quickly extract the needed information from the data to address earthquake emergencies, a topic-words detection model of earthquake emergency microblog messages is studied. First, a case analysis method is used to analyze microblog information after earthquake events. An earthquake emergency information classification hierarchy is constructed based on public demand. Then, subject sets of different granularities of earthquake emergency information classification are generated through the classification hierarchy. A detection model of new topic-words is studied to improve and perfect the sets of topic-words. Furthermore, the validity, timeliness, and completeness of the topic-words detection model are verified using 2201 messages obtained after the 2014 Ludian earthquake. The results show that the information acquisition time of the model is short. The validity of the whole set is 96.96%, and the average and maximum validity of single words are 78% and 100%, respectively. In the Ludian and Jiuzhaigou earthquake cases, new topic-words added to different earthquakes only reach single digits in validity. Therefore, the experiments show that the proposed model can quickly obtain effective and pertinent information after an earthquake, and the complete performance of the earthquake emergency information classification hierarchy can meet the needs of other earthquake emergencies.
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http://dx.doi.org/10.3390/ijerph18158000DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345666PMC
July 2021

Bioresorbable Depot for Sustained Release of Immunostimulatory Resiquimod in Suppressing Both Primary Triple-Negative Breast Tumors and Metastatic Occurrence.

Bioconjug Chem 2021 05 22;32(5):1008-1016. Epub 2021 Apr 22.

School of Bioengineering, Dalian University of Technology, No. 2 Linggong Road, Dalian 116024, China.

In light of immune facilities trafficking toward the pathological sites along upward gradient of immunostimulatory cytokines, a localized resiquimod (Toll-like receptor 7/8 agonist) release depot was manufactured for pursuit of precision immunostimulation toward intractable triple-negative breast carcinoma. In principle, resiquimod/poly(lactic--glycolic acid) microspheres were fabricated and embedded into injectable and biodegradable poly(ethylene glycol) (PEG)-based hydrogel. The subsequent investigations approved persistent retention of immunostimulatory resiquimod in tumors upon peritumoral administration, which consequently led to localized and consistent secretion of immunostimulatory cytokines. Initially, not only innate tumor phagocytosis but also adaptive antitumor immunities were successfully cultivated for suppression of the growth of primary solid tumors, more importantly, capable of inhibiting distant pulmonary metastasis, as evidenced by observation of enormous lymphocytes selectively gathering in the pulmonary artery. Hence, our presented study provided an important clinical indication of using immunostimulatory drugs to activate potent innate and adaptive antitumor immunities for precision antitumor therapy. Further immunomodulatory strategies, such as checkpoint blockage and tumor immunogenicity, could also be complementary for development of advanced antitumor immunotherapeutics in treatment of a number of intractable tumors.
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http://dx.doi.org/10.1021/acs.bioconjchem.1c00171DOI Listing
May 2021

Artesunate attenuates bone erosion in rheumatoid arthritis by suppressing reactive oxygen species via activating p62/Nrf2 signaling.

Biomed Pharmacother 2021 May 23;137:111382. Epub 2021 Feb 23.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address:

Accumulating studies have indicated that reactive oxygen species (ROS) may be implicated into the destructive pathological events of rheumatoid arthritis (RA). As an effective antioxidant, artesunate (ARS) was reported to exert antiarthritic effects. However, whether ARS attenuates the bone erosion during RA progression by regulating ROS production remains to be defined. To address this problem, the inhibitive effects of ARS on osteoclastogenesis were observed in vitro. Mechanically, ARS significantly inhibited the NFATc1 signaling accompanied by markedly suppressing ROS production, which was abnormally enhanced during the pathological process of bone erosion. In addition, ARS may function as a potent ROS scavenger and significantly elevate the expression of HO-1 and NQO1 by activating Nrf2. Moreover, p62 accumulation induced by ARS was responsible for the activation of Nrf2, while the knockdown of p62 in osteoclast precursor cells diminished the suppressive effect of ARS on ROS production during osteoclastogenesis. Consistently, we also demonstrated that ARS effectively suppressed ROS production, leading to the inhibition of arthritic bone destruction by activating antioxidant enzyme and Nrf2/p62 signaling in the knee and ankle tissues of CIA rats. Collectively, our data offer the convincing evidence that ARS may inhibit osteoclastogenesis and ameliorate arthritic bone erosion through suppressing the generation of ROS via activating the p62/Nrf2 signaling.
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http://dx.doi.org/10.1016/j.biopha.2021.111382DOI Listing
May 2021

Sinomenine protects bone from destruction to ameliorate arthritis via activating p62-Keap1-Nrf2 feedback loop.

Biomed Pharmacother 2021 Mar 1;135:111195. Epub 2021 Jan 1.

State Key Laboratory of Quality Research in Chinese Medicine/Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China; Joint Laboratory for Translational Cancer Research of Chinese Medicine of the Ministry of Education of the People's Republic of China, Macau University of Science and Technology, Macau, China; Guangdong-Hong Kong-Macao Joint Laboratory of Respiratory Infectious Disease, Macau University of Science and Technology, Macau, China. Electronic address:

Disease-modifying antirheumatic drugs (DMARDs) are the first line medications to treat rheumatoid arthritis (RA), a chronic and systemic autoimmune disease affecting multiple joints. Sinomenine (SIN) is thought a natural DMARD (nDMARD) and effectively utilized to treat RA in clinic for several decades in China. Here we reported that it is not methotrexate (MTX), a representative drug of DMARDs, but SIN protected joints from destruction to alleviate the symptoms of the mice with arthritis, indicating that the underlying mechanism of SIN is different from MTX to treat arthritis. Due to the dominate role of synovium fibroblasts in the joint destruction of arthritis, we applied synovium fibroblasts derived from RA patients (RASFs) to investigate the anti-arthritic effect and explore the underlying mechanism of SIN. We found that SIN significantly inhibited the secretion of IL-6 and IL-33 and ROS production in RASFs to mediate protective effect on bone destruction to mediate anti-arthritis effect. Underlying mechanistic study showed that SIN induced phosphorylation of p62 at Ser349 and Thr269/Ser272 to activate Keap1-Nrf2 signaling in RASFs. In line with the results, we then observed that the anti-arthritic effect of SIN was significantly attenuated in Nrf2 deficient (Nrf2) mice. Notably, we found that p62 expression and phosphorylation at Thr269/Ser272 remarkably reduced, while p62 phosphorylation at Ser351 was up-regulated in Nrf2 deficient mice compared to its wild littermates, indicating that Nrf2 probably negative regulates p62 phosphorylation at Ser351. Collectively, our findings demonstrate that SIN phosphorylated p62 at Ser351 (corresponding to human Ser349) to degrade Keap1 expression and accumulate Nrf2 expression, increased p62 expression and phosphorylation at Thr269/Ser272 to activate p62-Keap1-Nrf2 axis, and finally exerted anti-arthritic effect. The current study not only clarified the anti-arthritic characteristics of SIN but also provided the clue to elucidate the correlation of p62 phosphorylation sites and Nrf2 signaling activation.
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http://dx.doi.org/10.1016/j.biopha.2020.111195DOI Listing
March 2021

Inferences of individual differences in response to tripterysium glycosides across patients with Rheumatoid arthritis using a novel ceRNA regulatory axis.

Clin Transl Med 2020 Oct;10(6):e185

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, P. R. China.

Background: To identify biomarkers for guiding therapy and predicting clinical response of Tripterysium Glycosides Tablets (TGT) treatment is an urgent task due to individual differences in TGT response across rheumatoid arthritis (RA) patients. Competing endogenous RNA (ceRNA) regulatory system may influence drug response with involvement in diverse biological processes. Herein, we aimed to identify a TGT response-related ceRNA axis.

Methods: A TGT response-related ceRNA axis was screened according to clinical cohort-based RNA expression profiling, lncRNA-mRNA coexpression, and ceRNA network analyses. Its clinical relevance was evaluated by computational modeling. Regulatory mechanisms of ceRNA axis were also experimentally investigated.

Results: The ceRNA regulatory axis combined with lncRNA ENST00000494760, miR-654-5p, and C1QC was identified as a candidate biomarker for RA patients' response to TGT. Both ENST00000494760 and C1QC mRNA expression were significantly lower, while miR-654-5p expression was dramatically higher in TGT responders than nonresponders. Its clinical relevance was verified by computational modeling based on both independent clinical validation cohort and collagen-induced arthritis (CIA) mice. Mechanistically, miR-654-5p directly bound to the 3'-untranslated region of both ENST00000494760 and C1QC mRNA to inhibit their expression. Moreover, miR-654-5p suppressed C1QC mRNA expression, but ENST00000494760 bound to miR-654-5p and relieved its repression on C1QC mRNA, leading to RA aggressive progression and weak TGT response.

Conclusions: LncRNA ENST00000494760 overexpression may sponge miR-654-5p to promote C1QC expression in RA patients. This novel ceRNA axis may serve as a biomarker for screening the responsive RA patients to TGT treatment, which will allow improved personalized healthcare.
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http://dx.doi.org/10.1002/ctm2.185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7545341PMC
October 2020

Iodine nutrition status of women after 10 years of Lipiodol supplementation: a cross-sectional study in Xinjiang, China.

Br J Nutr 2021 Jul 8;126(1):9-21. Epub 2020 Oct 8.

Institute for Iodine Deficiency Disorders Control, Centre for Endemic Disease Control, Chinese Centre for Disease Control and Prevention, Harbin Medical University, Harbin City, Heilongjiang Province 150081, People's Republic of China.

This study examined the contribution of long-term use of Lipiodol capsules, as a supplement to iodised salt to the control of iodine deficiency disorders among women in Xinjiang of China. A total of 1220 women across Kashgar, Aksu, Turpan and Yili Prefectures were surveyed in 2017. Lipiodol capsules were administered twice yearly in Kashgar and once yearly in Aksu and Turpan, but not in Yili. Urinary iodine concentration (UIC), free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), thyroglobulin antibody, thyroid peroxidase antibody and thyroid volume values were assessed. All the women in the four areas were in a state of non-iodine deficiency by UIC. The UIC were higher than adequate in Kashgar and Aksu (619·4 v. 278·6 μg/l). Thyroid hormone levels differed significantly in Turpan and Yili (FT3: 4·4 v. 4·6 pmol/l, FT4: 13·8 v. 14·2 pmol/l, TSH: 2·0 v. 2·7 mIU/l), but did not differ significantly in Kashgar, Aksu and Yili. The four areas did not differ significantly with regard to thyroid nodules, autoimmune thyroiditis or goitre. However, the detection rates of subclinical hypothyroidism (16·6 %) and total thyroid dysfunction (25·4 %) were higher among women in Yili. The supplementation with Lipiodol capsules had improved the iodine nutrition status of women in iodine-deficient areas of Xinjiang since 2006. To avoid negative effects of excess iodine, we suggest a gradual discontinuation of Lipiodol capsules in women with special needs based on the existing iodine nutrition level of local women.
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http://dx.doi.org/10.1017/S0007114520003918DOI Listing
July 2021

Radiomic signatures derived from multiparametric MRI for the pretreatment prediction of response to neoadjuvant chemotherapy in breast cancer.

Br J Radiol 2020 Nov 2;93(1115):20200287. Epub 2020 Sep 2.

Breast Disease Center, The Affiliated Hospital of Qingdao University, Qingdao 266000, Shandong, China.

Objectives: To investigate the ability of radiomic signatures based on MRI to evaluate the response and efficiency of neoadjuvant chemotherapy (NAC) for treating breast cancers.

Methods: 152 patients were included in this study at our institution between March 2017 and September 2019. All patients with breast cancer underwent a preoperative breast MRI and the Miller-Payne grading system was applied to evaluate response to NAC. Quantitative parameters were compared between patients with sensitive and insensitive responses to NAC and between those with pathological complete responses (pCR) and non-pCR. Four radiomic signatures were built based on T2W imaging, diffusion-weighted imaging, dynamic contrast-enhanced imaging and their combination, and radiomics scores (Rad-score) were calculated. The combination of the clinical factors and Rad-scores created a nomogram model. Multivariate logistic regression was performed to assess the association between MRI features and independent clinical risk factors.

Results: 20 features and 18 features were selected to build the radiomic signature for evaluating sensitivity and the possibility of pCR, respectively. The combined radiomic signature and nomogram model showed a similar discrimination in the training (AUC 0.91, 0.92, 95% confidence interval [CI], 0.85-0.96, 0.86-0.98) and validation (AUC 0.93, 0.91, 95% CI, 0.86-1.00, 0.82-1.00) sets. The clinical factor model exhibited reduced performance (AUC 0.74, 0.64, 95% CI, 0.64-0.84, 0.46-0.82) in terms of NAC sensitivity and pCR.

Conclusions: The combined radiomic signature and nomogram model exhibited potential predictive power for predicting effective NAC treatment which can aid in the prognosis and guidance of treatment regimens.

Advances In Knowledge: Identifying a means of assessing the efficacy of NAC before surgery can guide follow-up treatment and avoid chemotherapy-induced toxicity.
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http://dx.doi.org/10.1259/bjr.20200287DOI Listing
November 2020

The silent information regulator 1 pathway attenuates ROS-induced oxidative stress in Alzheimer's disease.

J Integr Neurosci 2020 Jun;19(2):321-332

Department of Neurology, Shijiazhuang No.1 Hospital, Shijiazhuang, 050011, P. R. China.

We show that down-regulation of circular ribonucleic acid 0001588 with small interfering-circular ribonucleic acid 0001588 mimics promoted caspase-3 and caspase-9 activity levels, increased lactate dehydrogenase activity levels, and reduced cell growth of in vitro model. Circular ribonucleic acid 0001588 plasmids increased circular ribonucleic acid 0001588 expressions and promoted cell growth and reduced activity levels of lactate dehydrogenase, caspase-3, and caspase-9 activity levels in vitro model of Alzheimer's disease. Then, circular ribonucleic acid 0001588 down-regulation also promoted reactive oxygen species production and oxidative stress (malonaldehyde), and reduced superoxide dismutase, glutathione, and glutathione peroxidase levels by suppressing of silent information regulator 1/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 in vitro. However, over-expression of circular ribonucleic acid 0001588 reduced reactive oxygen species production and malonaldehyde levels and increased superoxide dismutase, glutathione, and levels via activation signal pathway of silent information regulator 1/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway by miR-211-5p up-regulation in vitro. Over-expression of miR-211-5p attenuated the role of circular ribonucleic acid 0001588 on Alzheimer's disease-induced oxidative stress. Also, activation of the silent information regulator 1 pathway attenuated the antioxidative effects of circular ribonucleic acid 0001588 down-regulation on oxidative stress by activating silent information regulator 1/nuclear factor erythroid 2-related factor 2/heme oxygenase-1 in vitro. In conclusion, our findings indicated that circular ribonucleic acid 0001588 induced the silent information regulator 1/nuclear factor erythroid 2-related factor 2-dependent heme oxygenase-1 pathway to prevent oxidative stress by miR-211-5p in the rat model or in vitro model of a sporadic type of Alzheimer's disease. Therefore, the expression of the circular ribonucleic acid 0001588 gene was inhibited in rodent Alzheimer's disease model.
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http://dx.doi.org/10.31083/j.jin.2020.02.1151DOI Listing
June 2020

High fat diet impairs spermatogenesis by regulating glucose and lipid metabolism in Sertoli cells.

Life Sci 2020 Sep 29;257:118028. Epub 2020 Jun 29.

Department of Endocrinology and Metabolism, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250021, Shandong, China; Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Institute of Endocrinology and Metabolism, Shandong Academy of Clinical Medicine, Jinan, Shandong, China; Department of Endocrinology and Metabolism, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250021, China. Electronic address:

Aims: Sertoli cells (SCs) play an important role in the process of spermatogenesis. SCs provide energy for germ cells (GCs) and themselves through glycolysis and fatty acid oxidation (FAO) respectively. High fat diet (HFD) impairs spermatogenesis by damaging function of SCs, however whether HFD disrupts energy metabolism in SCs remains unclear.

Main Methods: To explore this hypothesis, we built male Wistar rat model fed on HFD and cultured rats' primary SCs with palmitic acid (PA). Rats' fertility and sperm quality were evaluated in vivo. Glycolysis, lactate production and mitochondrial respiration were assessed by using extracellular flux analyzer, and the expression of enzymes involved in glucose and FAO was analyzed by Real-Time PCR or Western Blotting.

Key Findings: The showed that the sperm concentration and pups per litter significantly decreased in rats fed on HFD compared to those rats fed on normal diet. There was an elevation of lactate levels in testicular tissue of rats fed on HFD and primary SCs exposed to PA. In vitro, PA increased glycolytic flux, and lactate production, and the levels of carnitine palmitoyltransferase I (CPT1) and long chain acyl-CoA dehydrogenase (LCAD) which were two key enzymes for fatty acid β oxidation. Further analysis showed that mitochondrial respiration was impaired by PA, followed by the decrease in ATP turnover, maximal respiration and the increase in proton leak.

Significance: Taken together, the elevated lactate level, lipid metabolism disorder and mitochondrial dysfunction caused by HFD lead to SCs dysfunction, which ultimately leads to decreased sperm quality.
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http://dx.doi.org/10.1016/j.lfs.2020.118028DOI Listing
September 2020

Correlation between imaging features and molecular subtypes of breast cancer in young women (≤30 years old).

Jpn J Radiol 2020 Nov 19;38(11):1062-1074. Epub 2020 Jun 19.

Department of Breast Radiology, Affiliated Hospital of Qingdao University, Qingdao University, No. 16, Jiangsu Road, Qingdao, 266100, Shandong Province, China.

Objectives: To analyze the features of digital mammography (DM) plus digital breast tomosynthesis (DBT), ultrasonography (US) and magnetic resonance imaging (MRI) of breast cancer in young women (≤30 years old) and the correlation with molecular subtypes.

Materials And Methods: We performed a retrospective study of imaging features of consecutive young women aged ≤30 years who were treated and surgically confirmed with breast cancer between January 2013 and December 2019 in our institution. All patients were Chinese women. DM + DBT and US were available for 170 lesions, MRI for 41 lesions. The imaging features were analysed by univariate and multivariate logistic regression analyses to find the predictive factors of the molecular subtypes.

Results: The predictive factors of the luminal B(HER2-) subtype (n = 51) were the mass with microcalcifications, irregular shape, spiculated margins, and shadowing posterior features (all P < 0.01). The predictive factors of the luminal B(HER2+) subtype (n = 26) were the spiculated margins (DBT + DM), angular margins (US), shadowing posterior features, and high vascularity (all P < 0.05). The predictive factors of the luminal A subtype (n = 37) were the mass without microcalcifications, spiculated margins, shadowing posterior features, and low vascularity (all P < 0.05). The predictive factors of the triple-negative subtype (n = 31) were the mass without microcalcifications, oval/round shape, circumscribed margins, enhancement of posterior features, and rim enhancement (MRI) (all P < 0.005). The predictive factors of the human-epidermal-growth-factor-receptor-2-enriched subtype (n = 26) were the only microcalcifications, microlobulated margins, and combined posterior feature (all P < 0.05).

Conclusion: Compared with the general population of breast cancer, this young female population presents a different molecular phenotype distribution. Some imaging features of breast cancer in young women ≤30 years old can be used to predict certain tumor molecular subtypes.
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http://dx.doi.org/10.1007/s11604-020-01001-8DOI Listing
November 2020

Prevention and Control of Iodine Deficiency Disorders - China, 1995-2020.

China CDC Wkly 2020 May;2(20):345-349

1 Centre for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China.

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http://dx.doi.org/10.46234/ccdcw2020.090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8393046PMC
May 2020

Identification of the Prognosis-Related lncRNAs and Genes in Gastric Cancer.

Front Genet 2020 11;11:27. Epub 2020 Feb 11.

Department of Gastric Surgery, Cancer Hospital of China Medical University, Liaoning, China.

Gastric cancer is a common malignant tumor with high occurrence and recurrence and is the leading cause of death worldwide. However, the prognostic value of protein-coding and non-coding RNAs in stage III gastric cancer has not been systematically analyzed. In this study, using TCGA data, we identified 585 long noncoding RNAs (lncRNAs) and 927 protein-coding genes (PCGs) correlated with the overall survival rate of gastric cancer. Functional enrichment analysis revealed that the prognostic genes positively correlated with death rates were enriched in pathways, including gap junction, focal adhesion, cell adhesion molecules (CAMs), and neuroactive ligand-receptor interaction, that are involved in the tumor microenvironment and cell-cell communications, suggesting that their dysregulation may promote the tumor progression. To evaluate the performance of the prognostic genes in risk prediction, we built three multivariable Cox models based on prognostic genes selected from the prognostic PCGs and lncRNAs. The performance of the three models based on features from only PCGs or lncRNAs or from all prognostic genes were systematically compared, which revealed that the features selected from all the prognostic genes showed higher performance than the features selected only from lncRNAs or PCGs. Furthermore, the multivariable Cox regression analysis revealed that the stratification with the highest performance was an independent prognostic factor in stage III gastric cancer. In addition, we explored the underlying mechanism of the prognostic lncRNAs in the Cox model by predicting the lncRNA and protein interaction. Specifically, was predicted to interact with and , which could also interact with cancer-related proteins, including and , suggesting that CTD-2218G20.2 might participate in the cancer progression these cancer-related proteins. In summary, the systematic analysis of the prognostic lncRNAs and PCGs was of great importance to the understanding of the progression of stage III gastric cancer.
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http://dx.doi.org/10.3389/fgene.2020.00027DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7027194PMC
February 2020

Deciphering the chemical profile and pharmacological mechanisms of Baihu-Guizhi decoction using ultra-fast liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry coupled with network pharmacology-based investigation.

Phytomedicine 2020 Feb 23;67:153156. Epub 2019 Dec 23.

Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. Electronic address:

Background: Baihu-Guizhi decoction (BHGZD) has been extensively used for the treatment of rheumatoid arthritis (RA) with a satisfying therapeutic effect. However, the material basis and the underlying mechanisms of BHGZD against RA have not been fully elucidated.

Purpose: To investigate the chemical profile and the pharmacological mechanisms of BHGZD against RA.

Methods: The chemical constituents containing in BHGZD were identified using UFLC-Q-TOF-MS/MS system, and the corresponding putative targets were predicted. Then, the differentially expressed genes (DEGs) between adjuvant-induced arthritis (AIA) and normal control groups were identified using microarray analysis. After constructing the interaction network of "RA-related gene-BHGZD putative target", BHGZD candidate targets against RA were screened by topological analysis and further experimentally validated based on AIA rat model.

Results: A total of 41 chemical constituents were identified in the water extract of BHGZD, which were predicted to hit 1312 putative targets. Additionally, 26 DEGs between the AIA and normal control groups were defined as "RA-related genes", which were functionally involved into the imbalance of "inflammation-immune" system during RA progression. On the basis of the topological importance in the network of "RA-related gene-BHGZD putative target", 177 BHGZD candidate targets against RA were identified. Among them, TLR4, c-Fos/AP-1, IL2 and TNF had direct interactions with each other and also function as crucial components of toll-like receptor and T cell receptor signaling pathways, which may play important roles in maintaining the balance of "inflammation-immune" system. Experimentally, we verified that BHGZD dose-dependently attenuated the severity, pathological changes, as well as mechanical, cold, and heat hypersensitivities during RA progression based on the AIA rat model. Further western blot analysis demonstrated that BHGZD significantly reduced the protein levels of TLR4, c-Fos/AP-1, IL2 and TNF, which were induced by RA modeling, in the inflamed joints of AIA rats (all p<0.05).

Conclusion: This study combining the chemical and transcriptomic profilings, target prediction, network calculation and experimental validations identifies the chemical constituents containing in BHGZD and offers the convincing evidence that BHGZD may ameliorate RA partially by restoring the balance of "inflammation-immune" system and subsequently reversing the pathological events during RA progression through regulating the TLR4-c-Fos-IL2-TNF axis.
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http://dx.doi.org/10.1016/j.phymed.2019.153156DOI Listing
February 2020

Maintenance of Primary Hepatocyte Functions In Vitro by Inhibiting Mechanical Tension-Induced YAP Activation.

Cell Rep 2019 12;29(10):3212-3222.e4

Department of Cell Biology, Second Military Medical University, Shanghai 200433, China; Department of Regenerative Medicine, College of Medicine, Tongji University, Shanghai 200433, China; Shanghai Key Laboratory of Cell Engineering, Second Military Medical University, Shanghai 200433, China. Electronic address:

Hepatocytes are the primary functional cells of the liver, performing its metabolic, detoxification, and endocrine functions. Functional hepatocytes are extremely valuable in drug discovery and evaluation, as well as in cell therapy for liver diseases. However, it has been a long-standing challenge to maintain the functions of hepatocytes in vitro. Even freshly isolated hepatocytes lose essential functions after short-term culture for reasons that are still not well understood. In the present study, we find that mechanical tension-induced yes-associated protein activation triggers hepatocyte dedifferentiation. Alleviation of mechanical tension by confining cell spreading is sufficient to inhibit hepatocyte dedifferentiation. Based on this finding, we identify a small molecular cocktail through reiterative chemical screening that can maintain hepatocyte functions over the long term and in vivo repopulation capacity by targeting actin polymerization and actomyosin contraction. Our work reveals the mechanisms underlying hepatocyte dedifferentiation and establishes feasible approaches to maintain hepatocyte functions.
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http://dx.doi.org/10.1016/j.celrep.2019.10.128DOI Listing
December 2019

LncRNA LINC01116 Promotes Cancer Cell Proliferation, Migration And Invasion In Gastric Cancer By Positively Interacting With lncRNA CASC11.

Onco Targets Ther 2019 3;12:8117-8123. Epub 2019 Oct 3.

Department of Gastric Surgery, Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang City, Liaoning Province 110042, People's Republic of China.

Purpose: The oncogenic roles of lncRNA LINC01116 have been reported in several types of cancer, while its involvement in gastric cancer is unknown. This study aimed to investigate the involvement of LINC01116 in gastric cancer.

Methods: Gene expression was detected by qPCR. Correlations were analyzed by linear regression. Overexpression and siRNA silencing techniques were used to analyze gene functions. Cell invasion and migration were analyzed by Transwell assays.

Results: LINC01116 and lncRNA CASC11 were both upregulated in cancer tissues compared to cancer-adjacent tissues. Expression levels of LINC01116 and CASC11 were increased with the increase in clinical stages. Expression levels of LINC01116 and CASC11 were positively correlated. Overexpression of LINC01116 mediated the upregulated CASC11 in gastric cancer cells, and CASC11 overexpression also led to overexpressed LINC01116. Overexpression of LINC01116 and CASC11 led to promoted invasion and migration of gastric cancer cells. Rescue experiments showed that CASC11 knockdown attenuated the effects of LINC01116 overexpression. Overexpression of LINC01116 failed to significantly affect cancer cell proliferation.

Conclusion: LINC01116 promoted cancer cell invasion and migration in gastric cancer by positively interacting with CASC11.
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http://dx.doi.org/10.2147/OTT.S208133DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6781852PMC
October 2019

Metformin Improves Fertility in Obese Males by Alleviating Oxidative Stress-Induced Blood-Testis Barrier Damage.

Oxid Med Cell Longev 2019 10;2019:9151067. Epub 2019 Sep 10.

Department of Endocrinology and Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan, Shandong 250021, China.

Background/aims: Obesity, which is related to increased oxidative stress in various tissues, is a risk factor for male infertility. Metformin is reported to have an antioxidant effect; however, the precise role of metformin in obesity-induced male infertility remains unknown. The current study is aimed at exploring the effects of metformin and characterizing its underlying mechanism in the fertility of obese males.

Methods: An obese male mouse model was generated by feeding mice with a high-fat diet; then, the mice were administered metformin in water for 8 weeks. Reproductive ability, metabolic parameters, and follicle-stimulating hormone (FSH) were assessed by cohabitation, enzymatic methods, and ELISA, respectively. Damage to the integrity of the blood-testis barrier (BTB), which ensures spermatogenesis, was assessed by transmission electron microscopy and immunofluorescence with a biotin tracer. Malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS) were employed for the assessments of oxidative stress. BTB-related proteins were measured by immunoblotting. Nuclear factor B (NF-B) was assessed by immunofluorescence.

Results: High-fat-diet-fed mice presented evident lipid metabolic disturbances, disrupted BTB integrity, and decreased reproductive function. Metformin alleviated the decrease in male fertility, decreased ectopic lipid deposition in the testis, and increased serum FSH levels. A further mechanistic analysis revealed that metformin ameliorated the high-fat-diet-induced injury to the BTB structure and permeability and restored the disordered BTB-related proteins, which might be associated with an improvement in oxidative stress and a recovery of NF-B activity in Sertoli cells (SCs).

Conclusion: Metformin improves obese male fertility by alleviating oxidative stress-induced BTB damage. These findings provide new insights into the effect of metformin on various diseases and suggest future possibilities in the treatment of male infertility.
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http://dx.doi.org/10.1155/2019/9151067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6754953PMC
March 2020

Obesity Promotes EAE Through IL-6 and CCL-2-Mediated T Cells Infiltration.

Front Immunol 2019 27;10:1881. Epub 2019 Aug 27.

Shanghai Institute of Immunology, Department of Immunology and Microbiology, Shanghai Key Laboratory for Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Growing evidence suggests that obesity is associated with the susceptibility and disease severity of multiple sclerosis. The chronic inflammation induced by obesity is believed to contribute to this process. However, the immune mechanisms connecting obesity to the prevalence and pathogenesis of MS are poorly defined. In this study, we show that high fat diet (HFD)-induced obese mice developed an exacerbated EAE as indicated by higher clinical scores and more severe pathological changes in spinal cord than the control mice fed with normal diet (ND), following immunization with myelin oligodendrocyte glycoprotein (MOG) 35-55 peptide. The exacerbation of EAE in HFD mice was associated with enhanced microglial activation and increased expansion of Th1 and Th17 cells. The HFD mice also showed aggravated disease in an adoptive T cell transfer EAE model. Mechanistically, HFD augmented the expression level of IL-6 and CCL-2 both in serum and brain, and blockade of IL-6 and CCL-2 signal ameliorated EAE with reduced T cells infiltration in CNS. Taken together, our results suggest that obesity promotes CNS inflammation in EAE through IL-6 and CCL-2 mediated the inflammatory cells infiltration.
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http://dx.doi.org/10.3389/fimmu.2019.01881DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6718738PMC
October 2020

Cyclophilin D participates in the inhibitory effect of high-fat diet on the expression of steroidogenic acute regulatory protein.

J Cell Mol Med 2019 10 1;23(10):6859-6871. Epub 2019 Aug 1.

Department of Endocrinology, Shandong Provincial Key Laboratory of Endocrinology and Lipid Metabolism, Shandong Provincial Hospital affiliated to Shandong University, Jinan, China.

Objective: The high-fat diet (HFD)-induced obesity is responsible for the testosterone deficiency (TD). However, the mechanism remains unknown. Mitochondrial homeostasis is proved to be important for maintaining the function of steroidogenic acute regulatory protein (StAR), the first rate-limiting enzyme in testosterone synthesis. As the key regulator of mitochondrial membrane permeability, cyclophilin D (CypD) plays a crucial role in maintaining mitochondrial function. In this study, we sought to elucidate the role of CypD in the expression of StAR affected by HFD.

Methods: To analyse the influence of CypD on StAR in vivo and in vitro, mouse models of HFD, CypD overexpression and CypD knockout (Ppif ) as well as Leydig cells treated with palmitic acid (PA) and CypD overexpression plasmids were examined with an array of metabolic, mitochondrial function and molecular assays.

Results: Compared with the normal diet mice, consistent with reduced testosterone in testes, the expressions of StAR in both mRNA and protein levels in HFD mice were down-regulated, while expressions of CypD were up-regulated. High-fat intake impaired mitochondrial function with the decrease in StAR in Leydig cells. Overexpression of CypD inhibited StAR expressions in vivo and in vitro. Compared with C57BL/6 mice with HFD, expressions of StAR were improved in Ppif mice with HFD.

Conclusions: Mitochondrial CypD involved in the inhibitory effect of HFD on StAR expression in testes.
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http://dx.doi.org/10.1111/jcmm.14569DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6787510PMC
October 2019

Adsorption Thermodynamics and Dynamics of Three Typical Dyes onto Bio-adsorbent Spent Substrate of .

Int J Environ Res Public Health 2019 02 26;16(5). Epub 2019 Feb 26.

Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Jiangsu Key Construction Laboratory for Food Safe and Nutritional Function, School of Life Science, Huaiyin Normal University, Changjiang West Road 111, Huai'an 223300, China.

Dyeing wastewater is very hard to treat, and adsorption could be a good choice. Spent substrate of (SSPE) was first used to adsorb malachite green, safranine T and methylene blue from aqueous solutions, and the corresponding adsorption isotherm, thermodynamics and dynamics models were simulated. More than 93% of the dyes were removed with solutions with 100 mg/L of initial dye concentration, 1 g of SSPE and pH of 6.0 after adsorption for 4 h. Freundlich isotherm models fit better the adsorption data than Langmuir models. Adsorption of the dyes onto SSPE was a spontaneous exothermic process based on an adsorption thermodynamics model. SSPE could adsorb the dyes rapidly, and a second-order kinetics model fit better with the adsorption data than a pseudo first-order kinetics model. Accordingly, SSPE could be a good bio-adsorbent for the removal of malachite green, safranine T and methylene blue from the aqueous solution.
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http://dx.doi.org/10.3390/ijerph16050679DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6427265PMC
February 2019

Spent substrate of Ganodorma lucidum as a new bio-adsorbent for adsorption of three typical dyes.

Bioresour Technol 2018 Oct 23;266:134-138. Epub 2018 Jun 23.

Jiangsu Key Laboratory for Eco-Agricultural Biotechnology around Hongze Lake, Jiangsu Key Construction Laboratory for Food Safe and Nutritional Function, School of Life Science, Huaiyin Normal University, Changjiang West Road 111, Huai'an 223300, China; Jiangsu Collaborative Innovation Center of Regional Modern Agriculture and Environmental Protection, Huaiyin Normal University, Changjiang West Road 111, Huai'an 223300, China.

Spent substrate of Ganodorma lucidum (SSGL), waste from cultivation of Ganoderma lucidum, was firstly used as a bio-adsorbent to adsorb three typical dyes malachite green, safranine T and methylene blue, and the adsorption thermodynamics and dynamics were also studied. SSGL was rich of hydroxyl group and carbonyl group, which had the potential to be an efficient bio-adsorbent for the three dyes removal from water and wastewater, and the treatment model should be eco-friendly. The experimental data fit well with the Langmuir and Freundlich isotherm, and the adsorption of dyes took place mainly on monolayer surface of SSGL. The experimental data fit also well with the adsorption thermodynamics, the adsorption were spontaneous and mainly a chemical adsorption. SSGL could adsorb the dyes rapidly and achieve an equilibrium in a short time, and the experimental data fit well with the second-order kinetics model.
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http://dx.doi.org/10.1016/j.biortech.2018.06.078DOI Listing
October 2018

Atomic force microscopy technique used for assessment of the anti-arthritic effect of licochalcone A via suppressing NF-κB activation.

Biomed Pharmacother 2018 Jul 7;103:1592-1601. Epub 2018 May 7.

State Key Laboratory of Quality Research in Chinese Medicine/Macau Institute for Applied Research in Medicine and Health, Macau University of Science and Technology, Macau, China. Electronic address:

Atomic force microscopy (AFM) is appropriately applied to the examination of hard surfaces and soft samples with extremely high resolution and ultrasensitive force, which cannot be obtained by other imaging techniques, including optical and electron microscopy. In the current study, AFM was employed to evaluate the anti-arthritic effect of licochalcone A (LCA), a flavonoid isolated from the root of Chinese medicinal herb Glycyrrhiza inflate, on rheumatoid arthritis synovial fibroblasts (RASFs) at the nanoscale for the first time. The morphology, ultrastructure and stiffness of RASFs was modified by LCA as determined by AFM, suggesting that LCA most likely exerts an anti-arthritic effect based on the key role of RASFs in the progression of RA. Further studies showed that the inhibitory effect of LCA on IκBα phosphorylation and degradation as well as on p65 nuclear translocation and phosphorylation contributed to altering the morphology, ultrastructure and stiffness of the RASF membrane. Interestingly, IKKβ phosphorylation was not detectable in RASFs, indicating that LCA altered the morphology, ultrastructure and stiffness of the RASF membrane by inhibiting NF-κB activation independent of IKKβ phosphorylation. Antigen-induced arthritis (AIA) was established in Sprague Dawley (SD) rats to validate the anti-arthritic effect of LCA, and LCA significantly decreased both the arthritis scores and paw swelling in the AIA rats, suggesting that LCA inhibits the progression and development of arthritis in vivo. Collectively, AFM provides evidence at the nanoscale to predict the anti-arthritic effect of drugs on RASFs, and LCA should be further investigated as a candidate agent for the treatment of arthritis.
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http://dx.doi.org/10.1016/j.biopha.2018.04.142DOI Listing
July 2018

A Comparative Study of Iodized Salt Programs: Shanghai and Switzerland.

Biol Trace Elem Res 2019 Jan 5;187(1):59-64. Epub 2018 May 5.

Institute of Iodine Deficiency Disorders Prevention and Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China.

Both Shanghai and Switzerland are developed regions with long-standing salt iodization programs and periodic monitoring. However, the two regions have their own approach to the implementation of the iodized salt policy. In Shanghai, monitoring was carried out every few years, using probability-proportional-to-size sampling technique to select 30 sampling units. Each unit consisted of more than 12 pregnant women and one randomly selected primary school. Urine samples were then taken from the chosen pregnant women and randomly recruited students of that school for iodine test. Data of Switzerland used in this comparative study was extracted from published researches. In Shanghai, the median urinary iodine concentration (UIC) in 2014 was 20% lower than in 1999 (P < 0.05). The median UIC of pregnant women in 2014 was 9.5% lower than that in 2011 (P < 0.05). In terms of iodized salt concentration, opposite to the increasing in Switzerland, it has exhibited a downward trend in Shanghai (P < 0.05). For the years monitored, the iodized salt concentration in Shanghai was significantly (P < 0.05) higher than in Switzerland. Though the UIC of children exhibited a downward trend in Shanghai (P < 0.05), it was still significantly (P < 0.05) higher than in Switzerland over the same monitoring period. However, the UIC in pregnant women was a totally different story, which was significantly (P < 0.05) lower in Shanghai than in Switzerland. Iodized salt is very important for maintaining sufficient iodine level in the population. Appropriate concentration of iodine in fortified salt needs to be decided according to local conditions. Special attention should be paid to the iodine level of pregnant women in Shanghai, and more education about iodine is necessary for the public health.
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http://dx.doi.org/10.1007/s12011-018-1370-6DOI Listing
January 2019

Assessment of thyroid function in children, adults and pregnant and lactating women after long-term salt iodisation measurements.

Br J Nutr 2018 06 27;119(11):1245-1253. Epub 2018 Mar 27.

1Key Lab of Etiology and Epidemiology,Education Bureau of Heilongjiang Province & Ministry of Health,Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention,Harbin Medical University,No. 157Baojian Road,Nangang District,Harbin 150081,People's Republic of China.

Universal salt iodisation (USI) has been successfully implemented in China for more than 15 years. Recent evidence suggests that the definition of 'adequate iodine' (100-199 µg/l) be revised to 'sufficient iodine' (100-299 µg/l) based on the median urinary iodine concentration (MUI) in school-age children. The objective of this study was to determine the prevalence of thyroid dysfunction in populations after long-term salt iodisation and examine whether the definition of adequate iodine can be broadened to sufficient iodine based on the thyroid function in four population groups. A cross-sectional survey was conducted in six provinces in the northern, central and southern regions of China. Four population groups consisting of 657 children, 755 adults, 347 pregnant women and 348 lactating women were recruited. Three spot urinary samples were collected over a 10-d period and blood samples were collected on the 1st day. In the study, among the adults, pregnant women and lactating women, the prevalence rates of elevated thyroglobulin antibody and thyroid microsomal antibody levels were 12·4, 8·5 and 7·8 %, and 12·1, 9·1 and 9·1 %, respectively. Abnormally high thyroid dysfunction prevalence was not observed after more than 15 years of USI in China because the thyroid dysfunction rates were all <5 %. The recommended range should be cautiously broadened from adequate iodine to sufficient iodine according to the MUI of school-age children considering the high levels of hormones and antibodies in the other populations. Adults, particularly pregnant women positive for thyroid antibodies, should be closely monitored.
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http://dx.doi.org/10.1017/S0007114518000570DOI Listing
June 2018

A Comparison of Iodine Status in Children and Pregnant Women After a Policy Change in the Iodized Salt Standard in Shanghai, China.

Biol Trace Elem Res 2018 Oct 14;185(2):275-281. Epub 2018 Mar 14.

Institute of Iodine Deficiency Disorders Prevention and Control, Center for Endemic Disease Control, Chinese Center for Disease Control and Prevention, Harbin Medical University, Harbin, Heilongjiang, China.

In Shanghai, a new iodized salt standard was implemented in 2012. To provide evidence to the government, we compared iodine status before (35 mg/kg) and after (30 mg/kg) adjustment in vulnerable populations living in Shanghai. The probability-proportional-to-size sampling technique was used to select at least 360 pregnant women for urine iodine test and at least 1200 students for thyroid measurement and the household salt test. Of these students, at least 360 performed urine iodine test. The median thyroid volume and the median household salt iodine concentration of children aged 8-10 years were 1.80 ml and 24.8 mg/kg in 2015, and 0.97 ml and 28.3 mg/kg in 2011. The median urine iodine concentration (UIC) of pregnant women was 126.52 and 139.77 μg/L in 2015 and 2011. All differences were statistically significant (P < 0.05). The median UIC of students was 171.40 and 181.63 μg/L in 2015 and 2011, the difference was not statistically significant. Multivariate linear regression analysis showed that thyroid volume in children was associated with sex, age, region, and household salt iodized concentration. The current iodized salt concentration meets the basic needs of the population's iodine requirements except for pregnant women. Periodic monitoring is necessary particularly in vulnerable groups.
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http://dx.doi.org/10.1007/s12011-018-1257-6DOI Listing
October 2018

Cyclophilin D deficiency attenuates mitochondrial perturbation and ameliorates hepatic steatosis.

Hepatology 2018 07 9;68(1):62-77. Epub 2018 May 9.

Department of Endocrinology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China.

Physiological opening of the mitochondrial permeability transition pore (mPTP) is indispensable for maintaining mitochondrial function and cell homeostasis, but the role of the mPTP and its initial factor, cyclophilin D (CypD), in hepatic steatosis is unclear. Here, we demonstrate that excess mPTP opening is mediated by an increase of CypD expression induced hepatic mitochondrial dysfunction. Notably, such mitochondrial perturbation occurred before detectable triglyceride accumulation in the liver of high-fat diet-fed mice. Moreover, either genetic knockout or pharmacological inhibition of CypD could ameliorate mitochondrial dysfunction, including excess mPTP opening and stress, and down-regulate the transcription of sterol regulatory element-binding protein-1c, a key factor of lipogenesis. In contrast, the hepatic steatosis in adenoviral overexpression of CypD-infected mice was aggravated relative to the control group. Blocking p38 mitogen-activated protein kinase or liver-specific Ire1α knockout could resist CypD-induced sterol regulatory element-binding protein-1c expression and steatosis. Importantly, CypD inhibitor applied prior to or after the onset of triglyceride deposition substantially prevented or ameliorated fatty liver.

Conclusion: CypD stimulates mPTP excessive opening, subsequently causing endoplasmic reticulum stress through p38 mitogen-activated protein kinase activation, and results in enhanced sterol regulatory element-binding protein-1c transcription and hepatic steatosis. (Hepatology 2018;68:62-77).
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http://dx.doi.org/10.1002/hep.29788DOI Listing
July 2018
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