Publications by authors named "Miaomiao Chen"

87 Publications

Super-enhancer receives signals from the extracellular matrix to induce PD-L1-mediated immune evasion integrin/BRAF/TAK1/ERK/ETV4 signaling.

Cancer Biol Med 2021 Oct 9. Epub 2021 Oct 9.

Laboratory of Medical Science, School of Medicine, Nantong University, Nantong 226001, China.

Objective: PD-L1 and PD-L2 expression levels determine immune evasion and the therapeutic efficacy of immune checkpoint blockade. The factors that drive inducible PD-L1 expression have been extensively studied, but mechanisms that result in constitutive PD-L1 expression in cancer cells are largely unknown.

Methods: DNA elements were deleted in cells by CRISPR/Cas9-mediated knockout. Protein function was inhibited by chemical inhibitors. Protein levels were examined by Western blot, mRNA levels were examined by real-time RT-PCR, and surface protein expression was determined by cellular immunofluorescence and flow cytometry. Immune evasion was examined by T cell-mediated killing.

Results: We determined the core regions (chr9: 5, 496, 378-5, 499, 663) of a previously identified PD-L1L2-super-enhancer (SE). Through systematic analysis, we found that the E26 transformation-specific (ETS) variant transcription factor (ETV4) bound to this core DNA region but not to DNA surrounding PD-L1L2SE. Genetic knockout of ETV4 dramatically reduced the expressions of both PD-L1 and PD-L2. ETV4 transcription was dependent on ERK activation, and BRAF/TAK1-induced ERK activation was dependent on extracellular signaling from αvβ3 integrin, which profoundly affected ETV4 transcription and PD-L1/L2 expression. Genetic silencing or pharmacological inhibition of components of the PD-L1L2-SE-associated pathway rendered cancer cells susceptible to T cell-mediated killing.

Conclusions: We identified a pathway originating from the extracellular matrix that signaled integrin/BRAF/TAK1/ERK/ETV4 to PD-L1L2-SE to induce PD-L1-mediated immune evasion. These results provided new insights into PD-L1L2-SE activation and pathways associated with immune checkpoint regulation in cancer.
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http://dx.doi.org/10.20892/j.issn.2095-3941.2021.0137DOI Listing
October 2021

Author Correction: Identification and characterization of Piwi-interacting RNAs in human placentas of preeclampsia.

Sci Rep 2021 Sep 14;11(1):18652. Epub 2021 Sep 14.

Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

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http://dx.doi.org/10.1038/s41598-021-98274-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440604PMC
September 2021

The photoredox-catalyzed hydrosulfamoylation of styrenes and its application in the novel synthesis of naratriptan.

Chem Commun (Camb) 2021 Sep 9;57(72):9140-9143. Epub 2021 Sep 9.

State Key Laboratory of Elemento-Organic Chemistry, Research Institute of Elemento-Organic Chemistry, College of Chemistry, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China.

The hydrosulfamoylation of diverse aryl olefins provides facile access to alkylsulfonamides. Here we report a novel protocol utilizing radical-mediated addition and a thiol-assisted strategy to achieve the hydrosulfamoylation of diverse styrenes in modest to excellent yields under mild and economic reaction conditions. The methodology was found to provide an efficient and convenient approach for the synthesis of the anti-migraine drug naratriptan and it also can be used for the late-stage functionalization of natural products or medicines.
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http://dx.doi.org/10.1039/d1cc04225dDOI Listing
September 2021

Caveolin1: its roles in normal and cancer stem cells.

J Cancer Res Clin Oncol 2021 Sep 8. Epub 2021 Sep 8.

Department of Pathophysiology, Medical College, Nanchang University, 461 Bayi Road, Nanchang, China.

Purpose: Stem cells are characterized by the capability of self-renewal and multi-differentiation. Normal stem cells, which are important for tissue repair and tissue regeneration, can be divided into embryonic stem cells (ESCs) and somatic stem cells (SSCs) depending on their origin. As a subpopulation of cells within cancer, cancer stem cells (CSCs) are at the root of therapeutic resistance. Tumor-initiating cells (TICs) are necessary for tumor initiation. Caveolin1 (Cav1), a membrane protein located at the caveolae, participates in cell lipid transport, cell migration, cell proliferation, and cell signal transduction. The purpose of this review was to explore the relationship between Cav1 and stem cells.

Results: In ESCs, Cav1 is beneficial for self-renewal, proliferation, and migration. In SSCs, Cav1 exhibits positive or/and negative effects on stem cell self-renewal, differentiation, proliferation, migration, and angiogenic capacity. Cav1 deficiency impairs normal stem cell-based tissue repair. In CSCs, Cav1 inhibits or/and promotes CSC self-renewal, differentiation, invasion, migration, tumorigenicity ability, and CSC formation. And suppressing Cav1 promotes chemo-sensitivity in CSCs and TICs.

Conclusion: Cav1 shows dual roles in stem cell biology. Targeting the Cav1-stem cell axis would be a new way for tissue repair and cancer drug resistance.
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http://dx.doi.org/10.1007/s00432-021-03793-2DOI Listing
September 2021

A Dual-Nanozyme-Catalyzed Cascade Reactor for Enhanced Photodynamic Oncotherapy against Tumor Hypoxia.

Adv Healthc Mater 2021 Sep 8:e2101049. Epub 2021 Sep 8.

State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian, 116024, P. R. China.

Tumor hypoxia is a typical characteristic of tumor microenvironment (TME), which seriously compromises the therapeutic effect of photodynamic therapy (PDT). The development of nanozymes with oxygen-generation ability is a promising strategy to overcome the oxygen-dependent of PDT but remained a great challenge. Herein, a dual-nanozymes based cascade reactor HAMF is proposed to alleviate tumor hypoxia for enhanced PDT. The hollow mesoporous silica nanoparticles (HMSNs) are constructed as an excellent nanocarrier to load ultra-small gold nanoparticles (Au NPs) and manganese dioxide (MnO ) shell via in situ reduction method, and further coordination with an efficient photosensitizer 4-DCF-MPYM (4-FM), a thermally activated delayed fluorescence (TADF) fluorescein derivative. With the response to TME, MnO can catalyze endogenous H O into O and subsequently accelerating glucose oxidation by Au NPs to produce additional H O , which is reversely used as the substrate for MnO -catalyzed reaction, thereby constantly producing singlet oxygen ( O ) for enhanced PDT upon light irradiation. This work proposed a cascade reactor based on dual-nanozyme to relieve tumor hypoxia for effective tumor suppression, which may enrich the application of multi-nanozymes in biomedicine.
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http://dx.doi.org/10.1002/adhm.202101049DOI Listing
September 2021

Beclin 1 positively regulates osteoprotegerin-induced inhibition of osteoclastogenesis by increasing autophagy in vitro.

Differentiation 2021 Sep-Oct;121:35-43. Epub 2021 Aug 23.

Institutes of Agricultural Science and Technology Development, Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou, 225009, Jiangsu, PR China; College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, PR China; Jiangsu Key Laboratory of Zoonosis, Yangzhou, 225009, Jiangsu, PR China. Electronic address:

Osteoclastogenesis is induced by receptor activator of nuclear factor-κB ligand (RANKL) and macrophage colony-stimulating factor (M-CSF), and can be suppressed by osteoprotegerin (OPG). Beclin1 has a dual role in osteoclastogenesis. However, the role of Beclin1-mediated autophagy during OPG-induced inhibition of osteoclastogenesis remains unclear. Here, we found that Beclin1 and matrix metalloproteinase 9 (MMP-9) expression were increased during osteoclastogenesis. OPG (20, 40, and 80 ng/mL) decreased Src and MMP-9 expression, but augmented Beclin1 expression and fluorescence intensity. Similarly, treatment with the autophagy activator rapamycin increased Beclin1 expression during OPG-induced inhibition of osteoclastogenesis. Further, Beclin1 knockdown restored osteoclast numbers by reducing autophagy during OPG-induced inhibition of osteoclastogenesis. These results indicate that Beclin1 has a positive role during OPG-induced inhibition of osteoclastogenesis by regulating autophagy, which might provide a potential basis for osteoclastogenesis.
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http://dx.doi.org/10.1016/j.diff.2021.08.003DOI Listing
August 2021

CRISPR/Cas12a-Based Ultrasensitive and Rapid Detection of V617F Somatic Mutation in Myeloproliferative Neoplasms.

Biosensors (Basel) 2021 Jul 24;11(8). Epub 2021 Jul 24.

Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, China.

The V617F mutation is a major diagnostic, therapeutic, and monitoring molecular target of Philadelphia-negative myeloproliferative neoplasms (MPNs). To date, numerous methods of detecting the V617F mutation have been reported, but there is no gold-standard diagnostic method for clinical applications. Here, we developed and validated an efficient Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR associated protein 12a (Cas12a)-based assay to detect the V617F mutation. Our results showed that the sensitivity of the V617F/Cas12a fluorescence detection system was as high as 0.01%, and the V617F/Cas12a lateral flow strip assay could unambiguously detect as low as 0.5% of the V617F mutation, which was much higher than the sensitivity required for clinical application. The minimum detectable concentration of genomic DNA achieved was 0.01 ng/μL (~5 aM, ~3 copies/μL). In addition, the whole process only took about 1.5 h, and the cost of an individual test was much lower than that of the current assays. Thus, our methods can be applied to detect the V617F mutation, and they are highly sensitive, rapid, cost-effective, and convenient.
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http://dx.doi.org/10.3390/bios11080247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394843PMC
July 2021

Cordyceps polysaccharide marker CCP modulates immune responses via highly selective TLR4/MyD88/p38 axis.

Carbohydr Polym 2021 Nov 16;271:118443. Epub 2021 Jul 16.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, China.

Cordyceps, one of the most expensive natural health supplements, is popularly used to modulate immune function. However, little is known regarding the underlying mechanism of its immunomodulatory activity. We newly reported a Cordyceps quality marker CCP (Mw 433.778 kDa) which was characterized as a 1,4-α glucan by chemical and spectral analysis and is able to induce significant immune responses of macrophages. Herein, we further investigated the molecular mechanism of CCP's immunomodulatory effects. The results indicate that CCP modulates the TLR4/MyD88/p38 signaling pathway of macrophages, where TLR4 plays a crucial role as verified on TLR4-deficient (TLR4) bone marrow-derived macrophages (BMDMs) and TLR4 mice. These findings provide a precise understanding of the molecular mechanism of Cordyceps' immunomodulatory benefits.
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http://dx.doi.org/10.1016/j.carbpol.2021.118443DOI Listing
November 2021

Identification and characterization of Piwi-interacting RNAs in human placentas of preeclampsia.

Sci Rep 2021 08 3;11(1):15766. Epub 2021 Aug 3.

Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, China.

Preeclampsia is a common disease of pregnancy that poses a serious threat to the safety of pregnant women and the fetus; however, the etiology of preeclampsia is inconclusive. Piwi-interacting RNAs (piRNAs) are novel non-coding RNAs that are present at high levels in germ cells and are associated with spermatogenesis. Emerging evidence demonstrated that piRNA is expressed in a variety of human tissues and is closely associated with tumorigenesis. However, changes in the piRNA expression profile in the placenta have not been investigated. In this study, we used small RNA sequencing to evaluate the differences in piRNA expression profiles between preeclampsia and control patients and potential functions. Differential expression analysis found 41 up-regulated and 36 down-regulated piRNAs in preeclamptic samples. In addition, the functional enrichment analysis of piRNAs target genes indicated that they were related to the extracellular matrix (ECM) formation and tissue-specific. Finally, we examined the expression pattern of the PIWL family proteins in the placenta, and PIWL3 and PIWIL4 were the primary subtypes in the human placenta. In summary, this study first summarized the changes in the expression pattern of piRNA in preeclampsia and provided new clues for the regulatory role of piRNA in the human placenta.
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http://dx.doi.org/10.1038/s41598-021-95307-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8333249PMC
August 2021

Hidden blood loss and its risk factors in patients undergoing conventional laparoscopic surgery and laparoendoscopic single-site surgery for ovarian cystectomy.

Int J Gynaecol Obstet 2021 Jul 30. Epub 2021 Jul 30.

Department of Gynecology and Obstetrics, The Second Affiliated Hospital and Yuying, Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.

Objective: To quantify the volume of hidden blood loss (HBL) between conventional laparoscopic surgery (CLS) and laparoendoscopic single-site surgery (LESS) for ovarian cyst and to explore its risk factors.

Methods: A total of 310 patients who underwent CLS or LESS were enrolled in this study. The Nadler formula and Gross formula were used to calculate each patient's estimated blood volume and total blood loss, multiple linear regression analysis was applied to identify the risk factors.

Results: The HBL in LESS was more than in CLS (P = 0.000). Operative time (p = 0.015), pre-hematocrit (P = 0.002), pre-hemoglobin (P = 0.015), and pelvic adhesions (P = 0.037) were positively correlated with HBL in CLS. Intraoperative bleeding (P = 0.026), operative time (P = 0.000), pre-hematocrit (P = 0.042), CA125 (P = 0.047), and cyst volume (P = 0.012) were independent risk factors for HBL in LESS.

Conclusion: A large amount of HBL occurs in ovarian cystectomy surgery and cannot be ignored in clinical work; fully and correctly understanding HBL and exploring its causes can ensure the safety and improve the prognosis of patients.
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http://dx.doi.org/10.1002/ijgo.13842DOI Listing
July 2021

Efficacy of montmorillonite and vitamin AD combined with zinc preparation in children with diarrheal disease and its effect on inflammatory factors.

Am J Transl Res 2021 15;13(5):5428-5435. Epub 2021 May 15.

Department of Child Health Care, Anhui Children's Hospital Hefei 230001, Anhui Province, China.

Objective: To investigate the effect of montmorillonite and vitamin AD combined with zinc preparation in children with diarrheal disease and its effect on inflammatory factors.

Methods: A total of 156 children with diarrheal diseases admitted to our hospital from January 2018 to January 2020 were enrolled and divided into two groups (n=78 for each) using random number table. The control group (CG) was treated with montmorillonite, and the observation group (OG) was additionally treated with vitamin AD and zinc. Both groups completed 7 d of treatment and 3 months of follow-up to compare the efficacy rate, time to onset of symptom relief, inflammatory factor levels, T-lymphocyte levels, adverse drug reactions, and relapse rate.

Results: The efficacy rate of 7 d treatment in the OG was 94.87%, higher than that of 56.41% in the CG ( < 0.05). After intervention, the OG had normal frequency of defecation, shorter time for stool to return to normal appearance, shorter duration of antiemetic, antipyretic, antidiarrheal treatment and shorter hospital stay than those of the CG ( < 0.05). The OG exhibited lower levels of CRP, TNF-α, NO, and PCT and higher levels of SOD than the CG ( < 0.05). The OG had lower levels CD3 and CD4 at 7 d after treatment, lower CD8 levels and higher CD4/CD8 levels than the CG ( < 0.05). The relapse rate at 6 months after treatment in the OG was lower than that in the CG ( < 0.05).

Conclusion: The combination of montmorillonite, vitamin AD and zinc preparation can achieve higher short-time efficacy, shorten the time of disappearance of symptoms, reduce the level of inflammatory factors, and improve the level of T-lymphocytes, without increasing the incidence of adverse drug reactions.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8205834PMC
May 2021

Cas12a and Lateral Flow Strip-Based Test for Rapid and Ultrasensitive Detection of Spinal Muscular Atrophy.

Biosensors (Basel) 2021 May 14;11(5). Epub 2021 May 14.

Center for Medical Genetics & Hunan Key Laboratory of Medical Genetics, School of Life Sciences, Central South University, Changsha 410078, China.

Spinal muscular atrophy (SMA) is characterized by severe lethality and irreversible progression. Early diagnosis of SMA is of more practical significance with the emergence of effective therapy. However, existing techniques to identify SMA patients rely on cumbersome instruments, hindering their accessibility and application. An SMA-Cas12a-strip assay was developed with the integration of Cas12a-based nucleic acid detection, isothermal amplification, and lateral flow strip. The analytical performance of the assay was assessed with clinical samples. To explore its extensible utility, various specimens were tested. Validated with 168 clinical samples, the sensitivity and specificity of the SMA-Cas12a-strip assay were both 100%. The minimum detectable concentration of genomic DNA containing the target gene achieved 526 aM. The assay was compatible with specimens from several sources, and the turnaround time could be within 1.5 h. We developed a simple, cost-effective, and highly sensitive and specific assay to detect SMA patients. With little and field-portable equipment, the assay holds great promise in the detection of SMA patients, particularly in low-resource regions.
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http://dx.doi.org/10.3390/bios11050154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8153588PMC
May 2021

The endoribonuclease N4BP1 prevents psoriasis by controlling both keratinocytes proliferation and neutrophil infiltration.

Cell Death Dis 2021 05 14;12(5):488. Epub 2021 May 14.

Department of Pathogenic Biology, School of Medicine, Nantong University, 226001, Jiangsu, China.

Psoriasis is a common chronic skin disease, characterized by abnormal interplay between hyperproliferative epidermal keratinocytes and self-reactive immune cells with not fully addressed molecular mechanism. N4BP1 (NEDD4-binding protein 1) is considered as an immune regulator for a long time but its physiological role is not determined yet. Here, we found that the expression of N4BP1 in skin was highest among all 54 tested tissues, and its expression was further upregulated in psoriatic skin. N4BP1-deficient mice exhibited normal grossly, but developed severe and prolonged IMQ-induced psoriasis-like disease comparing to controls. N4BP1 mainly expressed in keratinocytes and located on nucleus. Up- but not downregulated genes in N4BP1-deficient skin were specifically enriched in keratinocyte proliferation and differentiation. The proliferation of N4BP1-deficient primary keratinocytes was faster compared to that of controls. The upregulated genes upon ablation of N4BP1 were highly enriched in targets of AP-1 transcription factor. Knocking out N4BP1 resulted in upregulation of JunB and FosB, and conversely, overexpression of N4BP1 greatly reduced their expression. Furthermore, N4BP1 binds with JunB and FosB encoding mRNAs and greatly reduces their stability. In addition, with a high expression in neutrophils, N4BP1 limits survival of neutrophils in blood and infiltration of neutrophils in psoriatic skin by targeting CXCL1, CCL20, and S100A8. These findings demonstrate that N4BP1 controls the proper function of keratinocytes and neutrophils by negatively regulating JunB, FosB, and CXCL1, respectively, and that is critical for psoriasis prevention.
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http://dx.doi.org/10.1038/s41419-021-03774-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8121926PMC
May 2021

Recyclable and Magnetically Functionalized Metal-Organic Framework Catalyst: IL/[email protected] for the Cycloaddition Reaction of CO with Epoxides.

ACS Appl Mater Interfaces 2021 May 9;13(19):22836-22844. Epub 2021 May 9.

School of Chemistry, Faculty of Chemical, Environmental and Biological Science and Technology, Dalian University of Technology, Dalian 116023, P.R. China.

A recyclable and magnetic nanocomposite catalyst (IL/[email protected]) was synthesized via grafting ionic liquid (IL) [AEMIm]BF into magnetically functionalized metal-organic framework [email protected] in a water-ethanol media. The properties of IL/[email protected] were fully characterized by powder X-ray diffraction, electron microscopy, Fourier-transform infrared spectroscopy, nitrogen adsorption-desorption, density-functional theory, and a magnetic property measurement system. IL/[email protected] showed high activity in the solvent-free cycloaddition of CO with epoxides under mild conditions. Furthermore, the catalyst can be easily separated from the reaction mixture, and the recycled catalyst maintained high performance for several cycles. The synergistic effect of the Lewis acid and base sites in IL/[email protected] contributes to its greater reactivity than individual IL or HKUST-1.
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http://dx.doi.org/10.1021/acsami.1c03345DOI Listing
May 2021

A Novel D-A-D Photosensitizer for Efficient NIR Imaging and Photodynamic Therapy.

Chembiochem 2021 Jun 7;22(12):2161-2167. Epub 2021 May 7.

Institute of Molecular Science and Engineering, Institute of Frontier and Interdisciplinary Science, Shandong University, 266237, Qingdao, Shandong, P. R. China.

Photodynamic therapy (PDT) has attracted great interest in cancer theranostics owing to its minimal invasiveness and low side effect. In PDT, photosensitizers are indispensable components that generate cytotoxic reactive oxygen species (ROS). Tremendous efforts have been devoted to optimizing the photosensitizer with enhanced ROS efficiency. However, to improve the precision and controllability for PDT, developing NIR imaging-guided photosensitizers are still urgent and challenging. Here, we have designed a novel photosensitizer 2Cz-BTZ which integrated with intense NIR emission and photoinduced singlet oxygen O generation capabilities. Moreover, after loading the photosensitizers 2Cz-BTZ into biocompatible amphiphilic polymers F127, the formed [email protected] nanoparticles (NPs) exhibited good photoinduced therapy as well as long-term in vivo imaging capabilities. Under these merits, the [email protected] NPs showed NIR imaging-guided PDT, which paves a promising way for spatiotemporally precise tumor theranostics.
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http://dx.doi.org/10.1002/cbic.202100107DOI Listing
June 2021

Opposing functions of β-arrestin 1 and 2 in Parkinson's disease via microglia inflammation and Nprl3.

Cell Death Differ 2021 Jun 8;28(6):1822-1836. Epub 2021 Mar 8.

Jiangsu Key Laboratory of Neurodegeneration, Department of Pharmacology, Nanjing Medical University, 818 Tianyuan East Road, Nanjing, 211166, Jiangsu, China.

Although β-arrestins (ARRBs) regulate diverse physiological and pathophysiological processes, their functions and regulation in Parkinson's disease (PD) remain poorly defined. In this study, we show that the expression of β-arrestin 1 (ARRB1) and β-arrestin 2 (ARRB2) is reciprocally regulated in PD mouse models, particularly in microglia. ARRB1 ablation ameliorates, whereas ARRB2 knockout aggravates, the pathological features of PD, including dopaminergic neuron loss, neuroinflammation and microglia activation in vivo, and microglia-mediated neuron damage in vitro. We also demonstrate that ARRB1 and ARRB2 produce adverse effects on inflammation and activation of the inflammatory STAT1 and NF-κB pathways in primary cultures of microglia and macrophages and that two ARRBs competitively interact with the activated form of p65, a component of the NF-κB pathway. We further find that ARRB1 and ARRB2 differentially regulate the expression of nitrogen permease regulator-like 3 (Nprl3), a functionally poorly characterized protein, as revealed by RNA sequencing, and that in the gain- and loss-of-function studies, Nprl3 mediates the functions of both ARRBs in microglia inflammatory responses. Collectively, these data demonstrate that two closely related ARRBs exert opposite functions in microglia-mediated inflammation and the pathogenesis of PD which are mediated at least in part through Nprl3 and provide novel insights into the understanding of the functional divergence of ARRBs in PD.
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http://dx.doi.org/10.1038/s41418-020-00704-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184754PMC
June 2021

Recent advances of redox-responsive nanoplatforms for tumor theranostics.

J Control Release 2021 04 1;332:269-284. Epub 2021 Mar 1.

State Key Laboratory of Fine Chemicals, School of Chemical Engineering, Dalian University of Technology, Dalian 116024, People's Republic of China; Institute of Molecular Sciences and Engineering, Shandong University, Qingdao 266237, People's Republic of China. Electronic address:

Nano-biotechnologies which combine diagnosis with therapy in an integrated nanoplatform provide a promising prospect for cancer theranostics. Currently, the development of personalized medicine requires the exploitation of "smart" theranostic nanoplatforms with specific targeting, precise cargoes release, non-invasive therapeutics for cancers and so on. High levels of hydrogen peroxide (HO) and glutathione (GSH) are prominent features of tumor microenvironment (TME), which are distinctly different from healthy tissues. Accordingly, extensive redox-responsive theranostic nanoplatforms have been exploited by modulating intracellular redox homeostasis. In this review, we first summarized the recent advances of overexpressed HO- and antioxidant GSH-responsive nanoplatforms for tumor diagnose and treatment. Then, the strategies by synergistically boosting reactive oxygen species (ROS) production and GSH depletion for amplifying oxidative stress are highlighted. At last, the prospects and controversies of stimuli-driven nanotheranostics are also discussed for future development.
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http://dx.doi.org/10.1016/j.jconrel.2021.02.030DOI Listing
April 2021

Dietary and serum selenium in coronary heart disease and all-cause mortality: An international perspective.

Asia Pac J Clin Nutr 2020 ;29(4):827-838

The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong, China. Email: Email:

Background And Objectives: The objective of this study was to explore the associations of dietary selenium and serum selenium concentration with coronary heart disease (CHD) prevalence and all-cause mortality among participants in United States.

Methods And Study Design: Using data collected from the National Health and Nutrition Examination Survey (NHANES) 1999-2006, 17867 individuals were included. Logistic regression analyses were used to explore the associations between dietary selenium intake and serum selenium concentration and prevalent of CHD. Multivariable Cox regression was used to identify the association between dietary selenium intake and all-cause mortality. The nonlinear relationships were assessed using generalized additive models.

Results: A U-shaped association between dietary intake of selenium and all-cause mortality was observed. Compared with the lowest quartile, the second quartile of dietary intake of selenium was inversely associated with all-cause mortality (Hazard ratio [HR]: 0.802, 95% confidence interval [CI]: 0.658, 0.977, p=0.029). There was no evidence of association between dietary selenium intake and CHD risk (Odds ratio [OR]: 1.001, 95% CI: 0.999, 1.003, p=0.206). Furthermore, serum selenium concentration was negatively associated with CHD risk (OR: 0.989, 95% CI: 0.981, 0.997, p=0.006). Comparing with the lowest quartile, participants with the highest serum selenium concentration had a statistically significant decreased prevalence of CHD, with OR (95% CI) of 0.417 (0.259, 0.669) (p<0.001). The smoothing curve also showed a non-linear relationship between serum selenium and risk of CHD.

Conclusions: This analysis suggested that a higher serum selenium concentration was associated with reduced risk of CHD, and that the relationship was non-linear. In addition, an appropriate dietary selenium intake might reduce all-cause mortality.
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http://dx.doi.org/10.6133/apjcn.202012_29(4).0019DOI Listing
January 2020

Hepatocellular Senescence: Immunosurveillance and Future Senescence-Induced Therapy in Hepatocellular Carcinoma.

Front Oncol 2020 27;10:589908. Epub 2020 Nov 27.

Institute for Regenerative Medicine, Shanghai East Hospital, School of Life Sciences and Technology, Tongji University, Shanghai, China.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. The lack of effective targeted drugs has become a challenge on treating HCC patients. Cellular senescence is closely linked to the occurrence, development, and therapy of tumor. Induction of cellular senescence and further activation of immune surveillance provides a new strategy to develop HCC targeted drugs, that is, senescence-induced therapy for HCC. Precancerous hepatocytes or HCC cells can be induced into senescent cells, subsequently producing senescence-associated secretory phenotype (SASP) factors. SASP factors recruit and activate various types of immune cells, including T cells, NK cells, macrophages, and their subtypes, which carry out the role of immune surveillance and elimination of senescent cells, ultimately preventing the occurrence of HCC or inhibiting the progression of HCC. Specific interventions in several checkpoints of senescence-mediated therapy will make positive contributions to suppress tumorigenesis and progression of HCC, for instance, by applying small molecular compounds to induce cellular senescence or selecting cytokines/chemokines to activate immunosurveillance, supplementing adoptive immunocytes to remove senescent cells, and screening chemical drugs to induce apoptosis of senescent cells or accelerate clearance of senescent cells. These interventional checkpoints become potential chemotherapeutic targets in senescence-induced therapy for HCC. In this review, we focus on the frontiers of senescence-induced therapy and discuss senescent characteristics of hepatocytes during hepatocarcinogenesis as well as the roles and mechanisms of senescent cell induction and clearance, and cellular senescence-related immunosurveillance during the formation and progression of HCC.
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http://dx.doi.org/10.3389/fonc.2020.589908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732623PMC
November 2020

Overexpression of c-Fos reverses osteoprotegerin-mediated suppression of osteoclastogenesis by increasing the Beclin1-induced autophagy.

J Cell Mol Med 2021 01 4;25(2):937-945. Epub 2020 Dec 4.

Institutes of Agricultural Science and Technology Development, Joint International Research Laboratory of Agriculture and Agri-Product Safety of the Ministry of Education of China, Yangzhou University, Yangzhou, China.

Osteoclastogenesis requires the involvement of transcription factors and degrading enzymes, and is regulated by upstream and downstream signalling. However, c-Fos how regulates osteoclastogenesis through autophagy remain unclear. This study aimed to explore the role of c-Fos during osteoprotegerin (OPG)-mediated suppression of osteoclastogenesis. We found that the number of osteoclasts and the expression of c-Fos, MMP-9, CAⅡ, Src and p62 were decreased after treated with OPG, including attenuation the PI3K/Akt and the TAK1/S6 signalling pathways, but the expression of Beclin1 and LC3Ⅱ were increased. Knockdown of Beclin1 could reverse the expression of c-Fos and MMP-9 by activating the PI3K/Akt signalling pathway, but inhibiting the autophagy and the TAK1/S6 signalling pathway. In addition, inhibition of autophagy using the PI3K inhibitor LY294002 did not rescues OPG-mediated suppression of osteoclastogenesis, but caused reduction of the expression of c-Fos and CAⅡ by attenuating the autophagy, as well as the PI3K/Akt and the TAK1/S6 signalling pathways. Furthermore, continuous activation of c-Fos could reverse OPG-mediated suppression of osteoclastogenesis by activating the autophagy and the PI3K/Akt and the TAK1/S6 signalling pathways. Thus, overexpression of c-Fos could reverse OPG-mediated suppression of osteoclastogenesis via activation of Beclin1-induced autophagy, indicating c-Fos might serve as a new candidate for bone-related basic studies.
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http://dx.doi.org/10.1111/jcmm.16152DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7812271PMC
January 2021

Characteristics of online medical care consultation for pregnant women during the COVID-19 outbreak: cross-sectional study.

BMJ Open 2020 11 17;10(11):e043461. Epub 2020 Nov 17.

Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

Objectives: This study described the needs of pregnant women and the contents of online obstetric consultation in representative areas with various severity of the epidemic in China.

Design: This was a cross- sectional study.

Setting: Yue Yi Tong (YYT), a free online communication platform that allows pregnant women to consult professional obstetricians.

Participants: All the pregnant women who used the YYT platform.

Intervention: From 10 to 23 February, we collected data on online obstetric consultations and participants' satisfaction through the YYT platform in the mild, moderate and severe epidemic areas which were defined according to the local confirmed cases. The primary outcomes were the reasons for online consultations by the severity of the epidemic. All the comparisons were performed using χ test. Statistical analysis was performed using SPSS V.24.

Results: A total of 2599 pregnant women participated in this study, of whom 448 (17.24%), 1332 (51.25%) and 819 (31.51%) were from the mild, moderate and severe epidemic areas, respectively. The distribution of the amount of online consultations was significantly different not only in different areas (p<0.001) but also in different trimesters (p<0.001). A total of 957 participants completed the satisfaction part of the survey. In this study, 77.95% of the participants used e-health for the first time, and 94.63% of the participants were completely or mostly satisfied with the online consultations.

Conclusions: The distribution of the amount of online consultations was significantly different not only in different areas but also in different trimesters. In any trimester, the amount of consultations on the second category (obstetric care-seeking behaviour) was the highest in the severe epidemic areas. The needs for online consultations were substantial. In order to prevent irreversible obstetric adverse events, an appropriate antenatal care contingency plan with e-health services is highly recommended during the Public Health Emergency of International Concern.
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http://dx.doi.org/10.1136/bmjopen-2020-043461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674021PMC
November 2020

Changes in physiology and immune system during pregnancy and coronavirus infection: A review.

Eur J Obstet Gynecol Reprod Biol 2020 Dec 16;255:124-128. Epub 2020 Oct 16.

Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, China. Electronic address:

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the 3rd epidemic coronavirus after severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). Since December 2019, the outbreak of the Coronavirus Disease 2019 (COVID-19) caused by SARS-CoV-2 has aroused great attention around the world. Pregnant women and their fetuses have been concerned as a high-risk population. We explained why pregnant women are susceptible to coronavirus in terms of their adaptive changes in physiology and immune system during pregnancy, and described the associations between maternal clinical symptoms, perinatal outcomes and coronavirus infections.
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http://dx.doi.org/10.1016/j.ejogrb.2020.10.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566677PMC
December 2020

Association between daytime napping duration and depression in middle-aged and elderly Chinese: evidence from the China Health and Retirement Longitudinal Study (CHARLS): A cross-sectional study in China.

Medicine (Baltimore) 2020 Oct;99(43):e22686

The Affiliated Yantai Yuhuangding Hospital of Qingdao University, Yantai, Shandong.

The effect of the afternoon napping duration on the risk of depression has not been well established, particularly with regard to sex and age differences. The present study examines the association between afternoon napping duration and depression stratified by sex and age among Chinese adults aged 45 years or older.The 2011 to 2012 survey of the China Health and Retirement Longitudinal Study was utilized, including 5746 participants. We conducted logistic regression with the overall sample and subjects stratified by sex and age.Elderly men with short napping (<30 minutes) had lower odds of having depression symptoms compared with those with no napping group (OR = 0.66, 95% CI = 0.44-0.97). In addition, the finding indicated that middle-aged women with long napping (≥90 min) had a marginally significant difference than those in reference, which showed a negative effect on depression (OR = 0.72, 95% CI = 0.51-1.01).Our findings revealed that extended daytime napping duration can decrease the risk of depression status among middle and elderly people. Moreover, relevant promotion measures should be adopted, such as a suitable rest environment and regular napping habits. The potential mechanism should be clarified by a longitudinal survey to examine the specific causality.
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http://dx.doi.org/10.1097/MD.0000000000022686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7581060PMC
October 2020

HDAC3i-Finder: A Machine Learning-based Computational Tool to Screen for HDAC3 Inhibitors.

Mol Inform 2021 03 23;40(3):e2000105. Epub 2020 Nov 23.

State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.

Histone deacetylase 3 (HDAC3) is a potential drug target for treatment of human diseases such as cancer, chronic inflammation, neurodegenerative diseases and diabetes. Machine learning (ML) as an essential cheminformatics approach has been widely used for QSAR modeling. However, none of them has been applied to HDAC3. To this end, we carefully compiled a set of 1098 compounds from the ChEMBL database that have been assayed against HDAC3 and calculated three different sets of molecular features for each compound, i. e. two-dimensional Mordred descriptors, MACCS keys (166 bits) and Morgan2 fingerprints (1024 bits). Five ML classifiers, i. e. k-Nearest Neighbour (KNN), Support Vector Machine (SVM), Random forest (RF), eXtreme Gradient Boosting (XGBoost) and Deep Neural Network (DNN) were trained on each feature set and optimized for classification. A total of 15 models were generated and carefully compared, among which the best-performing one was the XGBoost model based on the Morgan2 fingerprints, i. e. XGBoost_morgan2. Evaluated on a well-curated benchmarking set named MUBD-HDAC3, this model achieved a high early ROC enrichment (ROCE0.5 %: 41.02). A further retrospective screening of an annotated chemical library in PubChem demonstrated that the best model could identify 8 novel-scaffold HDAC3 inhibitors while assaying only 1 % of the compounds. To make this model accessible for the scientific community, we developed a python GUI application named HDAC3i-Finder to facilitate prospective screening for HDAC3 inhibitors. The source code of HDAC3i-Finder is available at https://github.com/jwxia2014/HDAC3i-Finder.
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http://dx.doi.org/10.1002/minf.202000105DOI Listing
March 2021

Vaginal delivery in women with COVID-19: report of two cases.

BMC Pregnancy Childbirth 2020 Oct 2;20(1):580. Epub 2020 Oct 2.

Department of Obstetrics, Maternal and Child Health Hospital of Hubei Province, No. 745 Wuluo Road, Hongshan District, Wuhan City, 430070, Hubei Province, China.

Background: During the ongoing global outbreak of COVID-19, pregnant women who are susceptible to COVID-19 should be highly concerned. The issue of vertical transmission and the possibility of neonatal infection is a major concern.

Case Presentation: Case 1: A 35-year-old pregnant woman with a gestational age of 37 weeks and 6 days was admitted to our hospital at the point of giving birth. Except for the abnormalities in her chest CT image, she was asymptomatic. She had an uncomplicated spontaneous vaginal delivery, and her infant was discharged home for isolation. Because of the positive result of the maternal swabs for SARS-CoV-2 obtained on the 2nd day after sampling, we transferred the mother to the designated hospital and followed up with her by telephone interviews. Luckily, it was confirmed on February 23 that the newborn did not develop any COVID-19 symptoms after observation for 14 days after birth. Case 2: Another pregnant woman, with a gestational age of 38 weeks and 2 days, was also admitted to our hospital because of spontaneous labor with cervical dilation of 5 cm. Since she had the typical manifestations of COVID-19, including cough, lymphopenia, and abnormal chest CT images, she was highly suspected of having COVID-19. Based on the experience from case 1, we helped the mother deliver a healthy baby by vaginal delivery. On the 2nd day after delivery, the maternal nasopharyngeal swab result was positive, while the infant's result was negative.

Conclusion: There is still insufficient evidence supporting maternal-fetal vertical transmission for COVID-19-infected mothers in late pregnancy, and vaginal delivery may not increase the possibility of neonatal infection.
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http://dx.doi.org/10.1186/s12884-020-03281-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7530846PMC
October 2020

Birth and birth-related obstetrical characteristics in southwestern China associated with the current adjustment of family planning policy: a 7-year retrospective study.

Sci Rep 2020 09 29;10(1):15949. Epub 2020 Sep 29.

Department of Obstetrics, The First Affiliated Hospital of Chongqing Medical University, No. 1 Youyi Road, Yuzhong District, Chongqing, 400016, China.

In China, the adjustment of the family planning policy was expected to increase the number of births and trigger a change in the demographic and obstetrical background of pregnant women. The policy itself, and corresponding background variations of the pregnant mothers, might have various influences on certain birth-related characteristics. Moreover, the adaption of the medical system to the policy needs to be demonstrated. To address these issues, over 50,000 individual records from January 2012 to December 2018 were collected from a large tertiary care centre of southwest China as a representative. The monthly numbers of deliveries and births showed stabilized patterns after remarkable upward trends. Policy-sensitive women, among whom older age and multiparity were typical features, contributed considerably to the remarkable additional births. Indeed, multivariable logistic regression analysis identified the child policy and these two background characteristics as factors influencing CS (caesarean section) rate and certain pregnancy complications or adverse outcomes. After the implementation of the two-child policy, a care provider was faced with fewer but more difficult cases. Briefly speaking, more individual-based studies on family planning policy and more efforts to improve obstetrical service are needed to better guide clinical practice in the new era.
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http://dx.doi.org/10.1038/s41598-020-73039-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525438PMC
September 2020

Exploring the Demographics and Clinical Characteristics Related to the Expression of Angiotensin-Converting Enzyme 2, a Receptor of SARS-CoV-2.

Front Med (Lausanne) 2020 19;7:530. Epub 2020 Aug 19.

Clinical Laboratory, Eye & ENT Hospital, Fudan University, Shanghai, China.

Coronavirus disease 2019 (COVID-19) was first reported in Wuhan, China, and has rapidly spread throughout the world. It has been reported that angiotensin-converting enzyme 2 (ACE2) is one of the major cellular entry receptors of SARS-CoV-2; thus, high ACE2 expression may increase susceptibility to infection. Therefore, we analyzed the expression of ACE2 in the blood to identify the individuals who may be susceptible to infection. In total, 229 subjects were enrolled in this study, and reverse transcription-quantitative polymerase chain reaction and ELISA assay was used to identify the level of ACE2 mRNA expression and ACE2 protein level in the blood. Demographic and clinical characteristics, including age, gender, weight, height, smoking habits, drinking habits, diabetes, and hypertension, were obtained using a face-to-face questionnaire. Independent Student's -test, Pearson's linear correlation, logistic regression analysis, and multiple linear regression correlation were performed to assess the association between these factors and the expression of ACE2. Higher level of ACE2 was observed in females, older subjects, subjects with hypertension, subjects with a cardiocerebrovascular disease, male smokers, and subjects with cancer ( < 0.05) than in other subjects. Multiple linear regression analysis showed that there is a statistically significant correlation between being a female and ACE2 expression (β = 0.550, < 0.001), between older age and ACE2 expression (β = 0.197, = 0.003), between smoking and ACE2 expression (β = 0.163, = 0.037), and between cancer and ACE2 expression (β = 0.265, < 0.001). Logistic regression analysis revealed that female subjects (odds ratio [OR] = 2.255, 95% confidence interval [CI] = 1.770-2.872), subjects with hypertension (OR = 1.264, 95% CI = 1.075-1.486), subjects with a cardiocerebrovascular disease (OR = 1.271, 95% CI = 1.023-1.579), subjects with cancer (OR = 1.695, 95% CI = 1.253-2.293), and subjects above 60 years of age (OR = 3.097, 95% CI = 1.078-8.896) are at an increased risk of infection due to their high expression of ACE2. The level of ACE2 is higher in females, older subjects, smokers, and subjects with cancer than in other subjects, indicating that some of which are at higher risk for the severe forms of COVID-19 when they are exposed to the SARS-Cov-2.
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http://dx.doi.org/10.3389/fmed.2020.00530DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7466575PMC
August 2020

Relationship Investigation between C(sp)-X and C(sp)-X Bond Energies Based on Substituted Benzene and Methane.

ACS Omega 2020 Aug 22;5(30):19304-19311. Epub 2020 Jul 22.

Key Laboratory of Theoretical Organic Chemistry and Function Molecule, Ministry of Education, School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201, Hunan Province, P. R. China.

The C-X bonds of organic compounds between group X and a saturated or unsaturated carbon atom differ in bond energy. To identify the causes of variation is of great significance in terms of bond nature understanding and bond energy estimation. In this paper, the electronegativity χ[X] of group X was calculated by the "valence electron equalized electronegativity" method. Then, χ[X] and the electronic effect constant of the substituent were taken as variables to establish equations for quantitative correlation between C(sp)-X and C(sp)-X for the calculation of C-X bond energies. The aim is make comparison between substituted methane, Me-X, and substituted benzene, Ph-X, as well as that between Me-X and substituted ethylene, CH-X. We conducted calculation over 40 compounds that contain different X groups, and the results reveal that the C(sp)-X and C(sp)-X bond energies are under the influence of a number of factors. In addition to the covalent properties of C and X atoms and χ[X], the bond energies of C(sp)-X (i.e., [C(sp)-X]) are under the influence of the field/inductive effect (σ[X]) and conjugated effect (σ[X]) of group X, with the former causing a decrease while the latter an increase of [C(sp)-X]. Using the acquired quantitative correlation equations and on the basis of a relatively rich set of measured [Me-X] data, we estimated [Ph-X] of Ph-X and [CH-X] of CH-X, and the estimation accuracy is within experimental uncertainty. Employing the above method, the [C(sp)-X] of 33 substituted benzenes, 53 substituted ethenes, and 82 α-substituted naphthalenes was estimated with satisfactory outcomes.
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http://dx.doi.org/10.1021/acsomega.0c02964DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409257PMC
August 2020

p53 positively regulates osteoprotegerin-mediated inhibition of osteoclastogenesis by downregulating TSC2-induced autophagy in vitro.

Differentiation 2020 Jul - Aug;114:58-66. Epub 2020 Jun 21.

College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, PR China; Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, PR China; Jiangsu Key Laboratory of Zoonosis, Yangzhou, 225009, Jiangsu, PR China; Joint International Research Laboratory of Agriculture and Agri-Product Safety, The Ministry of Education of China, Yangzhou University, Yangzhou, 225009, Jiangsu, PR China. Electronic address:

Osteoclasts are terminally multinucleated cells that are regulated by nuclear factor-activated T cells c1 (NFATc1), and are responsible for bone resorption while the tartrate resistant acid phosphatase (TRAP) enzymes releases into bone resorption lacunae. Furthermore, tumor suppressor p53 is a negative regulator during osteoclastogenesis. Osteoprotegerin (OPG) inhibits osteoclastogenesis and bone resorption by activating autophagy, however, whether p53 is involved in OPG-mediated inhibition of osteoclastogenesis remains unclear. In the current study, OPG could enhance the expression of p53 and tuberin sclerosis complex 2 (TSC2). Moreover, the expression of p53 is regulated by autophagy during OPG-mediated inhibition of osteoclastogenesis. Inhibition of p53 by treated with pifithrin-α (PFTα) causing augments of osteoclastogenesis and bone resorption, also reversed OPG-mediated inhibition of osteoclastogenesis by reducing the expression of TSC2. In addition, knockdown of TSC2 using siRNA could rescue OPG-mediated inhibition of osteoclastogenesis by reducing autophagy, which is manifested by the decrease of the expression of Beclin1 and the phosphorylation of mammalian target of rapamycin (mTOR) and ribosomal protein S6 kinase beta 1 (S6K1, also known as p70S6K). Collectively, p53 plays a critical role during OPG-mediated inhibition of osteoclastogenesis via regulating the TSC2-induced autophagy in vitro.
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http://dx.doi.org/10.1016/j.diff.2020.06.002DOI Listing
July 2021
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