Publications by authors named "Hui Shi"

704 Publications

Correspondence on "Update on the diagnosis and management of systemic lupus erythematosus" by Fanouriakis .

Ann Rheum Dis 2021 Aug 3. Epub 2021 Aug 3.

Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China

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http://dx.doi.org/10.1136/annrheumdis-2021-220897DOI Listing
August 2021

The Framingham risk score is associated with incident frailty, or is it?

BMC Geriatr 2021 Jul 31;21(1):448. Epub 2021 Jul 31.

Department of Medicine, Division of Geriatric Medicine and Gerontology, School of Medicine, Johns Hopkins University, 2024 E. Monument Street, Suite 2-700, Baltimore, MD, 21205, USA.

Backgrounds: Cardiovascular disease (CVD) risk factors are individually associated with frailty. This study examined whether Framingham CVD risk score (FRS) as an aggregate measure of CVD risk is associated with incident frailty among Chinese older adults.

Methods: This study used data from the China Health and Retirement Longitudinal Study. A sample of 3,618 participants aged 60 to 95 years and without CVD at baseline were followed for four years. FRS was calculated at baseline. Frailty status was defined as not-frail (0-2 criteria) or frail (3-5 criteria) based on the physical frailty phenotype consisting of five binary criteria (weakness, slowness, exhaustion, low activity level, and weight loss). After excluding subjects who were frail (n = 248) at baseline, discrete-time Cox regression was used to evaluate the relationship between FRS and incident frailty.

Results: During a median follow-up of 4.0 years, 323 (8 %) participants developed CVD and 318 (11 %) subjects had frailty onset. Higher FRS was associated with greater risk of incident frailty (HR: 1.03, 95 % CI: 1.00 to 1.06) after adjusting for education, marital status, obesity, comorbidity burden, and cognitive function. This association however was no longer significant (HR: 1.00, 95 % CI: 0.97 to 1.03) after additionally adjusting for age. These findings remained essentially unchanged after excluding subjects with depression (n = 590) at baseline or incident CVD (n = 323) during the 4-year follow-up.

Conclusions: The FRS was not independently associated with incident frailty after adjusting for chronological age. More research is needed to assess the clinical utility of the FRS in predicting adverse health outcomes other than CVD in older adults.
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http://dx.doi.org/10.1186/s12877-021-02387-4DOI Listing
July 2021

Value of High-Frequency Ultrasound for Differentiating Invasive Basal Cell Carcinoma from Non-invasive Types.

Ultrasound Med Biol 2021 Jul 17. Epub 2021 Jul 17.

Department of Medical Ultrasound, Shanghai Skin Disease Hospital, Ultrasound Research and Education Institute, Tongji University School of Medicine, Shanghai, China; Department of Medical Ultrasound & Tumor Minimally Invasive Treatment, Shanghai Tenth People's Hospital; Ultrasound Research and Education Institute, Clinical Research Center for Interventional Medicine, Tongji University School of Medicine, Shanghai, China; Shanghai Engineering Research Center of Ultrasound Diagnosis and Treatment; National Clinical Research Center for Interventional Medicine, Shanghai, China. Electronic address:

The purpose of the study was to evaluate the value of high-frequency ultrasound (HFUS) for differentiating invasive basal cell carcinomas (BCCs) from non-invasive BCCs. We established a prediction model based on ultrasound features and validated it further. One hundred patients in the pilot cohort and another 43 in the validation cohort were evaluated. All patients underwent HFUS examinations by the same radiologist, and then were divided on the basis of pathology into invasive and non-invasive types. With respect to growth pattern, 60.5% of invasive BCCs had an irregular pattern, whereas 89.5% of non-invasive BCCs had a nodular or crawling pattern (p < 0.001). As for the layers involved, the more invasive BCCs broke through the dermis compared with non-invasive BCCs (23.3% vs. 1.8%) (p < 0.001). With respect to intralesional hyperechoic spot distribution, invasive and non-invasive BCCs tended to be clustered and absent/scattered-like, respectively (55.8% vs. 91.2%) (p < 0.001). On the basis of the aforementioned features, a prediction model was established with accuracies of 84.0% and 76.7%, respectively, in the pilot and validation cohorts. HFUS holds promise for the differentiation of the invasiveness of BCCs and is helpful in its clinical management.
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http://dx.doi.org/10.1016/j.ultrasmedbio.2021.06.006DOI Listing
July 2021

Endothelium-protective, histone-neutralizing properties of the polyanionic agent defibrotide.

JCI Insight 2021 Jul 15. Epub 2021 Jul 15.

Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America.

Neutrophil-mediated activation and injury of the endothelium play a role in the pathogenesis of diverse disease states ranging from autoimmunity to cancer to COVID-19. Neutralization of cationic proteins (such as neutrophil extracellular trap/NET-derived histones) with polyanionic compounds has been suggested as a potential strategy for protecting the endothelium from such insults. Here, we report that the FDA-approved polyanionic agent defibrotide (a pleotropic mixture of oligonucleotides) directly engages histones and thereby blocks their pathological effects on endothelium. In vitro, defibrotide counteracted endothelial cell activation and pyroptosis-mediated cell death, whether triggered by purified NETs or recombinant histone H4. In vivo, defibrotide stabilized the endothelium and protected against histone-accelerated inferior vena cava thrombosis in mice. Mechanistically, defibrotide demonstrated direct and tight binding to histone H4 as detected by both electrophoretic mobility shift assay and surface plasmon resonance. Taken together, these data provide insights into the potential role of polyanionic compounds in protecting the endothelium from thromboinflammation with potential implications for myriad NET- and histone-accelerated disease states.
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http://dx.doi.org/10.1172/jci.insight.149149DOI Listing
July 2021

Inhibition of Calpain Alleviates Apoptosis in Coxsackievirus B3-induced Acute Virus Myocarditis Through Suppressing Endoplasmic Reticulum Stress.

Int Heart J 2021 Jul 6;62(4):900-909. Epub 2021 Jul 6.

Department of Cardiology, Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Shanghai Medical College of Fudan University.

Virus myocarditis (VMC) is a common cardiovascular disease and a major cause of sudden death in young adults. However, there is still a lack of effective treatments. Our previous studies found that calpain activation was involved in VMC pathogenesis. This study aims to explore the underlying mechanisms further. Neonatal rat cardiomyocytes (NRCMs) and transgenic mice overexpressing calpastatin (Tg-CAST), the endogenous calpain inhibitor, were used to establish VMC model. Hematoxylin and eosin and Masson staining revealed inflammatory cell infiltration and fibrosis. An ELISA array detected myocardial injury. Cardiac function was measured using echocardiography. CVB3 replication was assessed by capsid protein VP1. Apoptosis was measured by TUNEL staining, flow cytometry, and western blot. The endoplasmic reticulum (ER) stress-related proteins were detected by western blot. Our data showed that CVB3 infection resulted in cardiac injury, as evidenced by increased inflammatory responses and fibrosis, which induced myocardial apoptosis. Inhibiting calpain, both by PD150606 and calpastatin overexpression, could attenuate these effects. Furthermore, ER stress was activated during CVB3 infection. However, calpain inhibition could downregulate some ER stress-associated protein levels such as GRP78, pancreatic ER kinase-like ER kinase (PERK), and inositol-requiring enzyme-1α (IRE-1α), and ER stress-related apoptotic factors, during CVB3 infection. In conclusion, calpain inhibition attenuated CVB3-induced myocarditis by suppressing ER stress, thereby inhibiting cardiomyocyte apoptosis.
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http://dx.doi.org/10.1536/ihj.20-803DOI Listing
July 2021

Controlled dimerization of artificial membrane receptors for transmembrane signal transduction.

Chem Sci 2021 May 5;12(23):8224-8230. Epub 2021 May 5.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Biology, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University Changsha 410082 P. R. China

In biology, membrane-spanning proteins are responsible for the transmission of chemical signals across membranes, including the signal recognition-mediated conformational change of transmembrane receptors at the cell surface, and a trigger of an intracellular phosphorylation cascade. The ability to reproduce such biological processes in artificial systems has potential applications in smart sensing, drug delivery, and synthetic biology. Here, an artificial transmembrane receptors signaling system was designed and constructed based on modular DNA scaffolds. The artificial transmembrane receptors in this system are composed of three functional modules: signal recognition, lipophilic transmembrane linker, and signal output modules. Adenosine triphosphate (ATP) served as an external signal input to trigger the dimerization of two artificial receptors on membranes through a proximity effect. This effect induced the formation of a G-quadruplex, which served as a peroxidase-like enzyme to facilitate a signal output measured by either fluorescence or absorbance in the lipid bilayer vesicles. The broader utility of this modular method was further demonstrated using a lysozyme-binding aptamer instead of an ATP-binding aptamer. Therefore, this work provides a modular and generalizable method for the design of artificial transmembrane receptors. The flexibility of this synthetic methodology will allow researchers to incorporate different functional modules while retaining the same molecular framework for signal transduction.
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http://dx.doi.org/10.1039/d1sc00718aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8208304PMC
May 2021

Autoantibodies stabilize neutrophil extracellular traps in COVID-19.

JCI Insight 2021 Jun 24. Epub 2021 Jun 24.

Department of Internal Medicine, University of Michigan, Ann Arbor, United States of America.

The release of neutrophil extracellular traps (NETs) by hyperactive neutrophils is recognized to play an important role in the thromboinflammatory milieu inherent to severe presentations of COVID-19. At the same time, a variety of functional autoantibodies have been observed in individuals with severe COVID-19 where they likely contribute to immunopathology. Here, we aimed to determine the extent to which autoantibodies might target NETs in COVID-19 and, if detected, to elucidate their potential functions and clinical associations. We measured anti-NET antibodies in 328 individuals hospitalized with COVID-19 alongside 48 healthy controls. We found high anti-NET activity in the IgG and IgM fractions of 27% and 60% of patients, respectively. There was a strong correlation between anti-NET IgG and anti-NET IgM (r=0.4, p<0.0001). Both anti-NET IgG and IgM tracked with high levels of circulating NETs, impaired oxygenation efficiency, and high circulating D-dimer. Furthermore, patients who required mechanical ventilation had a greater burden of anti-NET antibodies than did those not requiring oxygen supplementation. Levels of anti-NET IgG (and to a lesser extent anti-NET IgM) demonstrated an inverse correlation with the efficiency of NET degradation by COVID sera. Furthermore, purified IgG from COVID sera with high levels of anti-NET antibodies impaired the ability of healthy control serum to degrade NETs. In summary, many individuals hospitalized with COVID-19 have anti-NET antibodies, which likely impair NET clearance and may potentiate SARS-CoV-2-mediated thromboinflammation.
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http://dx.doi.org/10.1172/jci.insight.150111DOI Listing
June 2021

Transcriptomic Landscape of Circulating Mononuclear Phagocytes in Langerhans Cell Histiocytosis at Single-cell Level.

Blood 2021 Jun 16. Epub 2021 Jun 16.

Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China.

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm caused by aberrant activation of the mitogen-activated protein kinase (MAPK) pathway. Circulating myeloid cells from patients often carry disease-associated mutations and can be differentiated into langerinhigh LCH-like cells in vitro, but their detailed immune-phenotypic and molecular profiles are lacking and could shed key insights into disease biology. Here we recruited 217 pediatric LCH patients and took blood and tissue samples for BRAFV600E analysis. Immune-phenotyping of the circulating Lin-HLA-DR+ immune population in 49 of these patients revealed that decreased frequency of pDC was significantly linked to disease severity. By single-cell RNA sequencing of samples from 14 patients, we identified key changes in expression of RAS-MAPK-ERK signaling-related genes and transcription factors in distinct members of the mononuclear phagocyte system in the presence of BRAFV600E. Moreover, treatment of patients with the BRAF inhibitor Dabrafenib resulted in MAPK cascade inhibition, inflammation prevention, and regulation of cellular metabolism within mononuclear phagocytes. Finally, we also observed elevated expression of RAS-MAPK-ERK signaling-related genes in a CD207+CD1a+ cell subcluster in skin. Taken together, our data extends the molecular understanding of LCH biology at single-cell resolution, which might contribute to improvement of clinical diagnostics and therapeutics, and aid in the development of personalized medicine approaches.
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http://dx.doi.org/10.1182/blood.2020009064DOI Listing
June 2021

Activation of Galanin Receptor 1 with M617 Attenuates Neuronal Apoptosis via ERK/GSK-3β/TIP60 Pathway After Subarachnoid Hemorrhage in Rats.

Neurotherapeutics 2021 Jun 4. Epub 2021 Jun 4.

Department of Neurosurgery, Loma Linda University, Loma Linda, CA, USA.

Subarachnoid hemorrhage (SAH) is a devastating cerebrovascular disease. Neuronal apoptosis plays an important pathological role in early brain injury after SAH. Galanin receptor 1 (GalR1) activation was recently shown to be anti-apoptotic in the setting of ischemic stroke. This study aimed to explore the anti-neuronal apoptosis effect of GalR1 activation after SAH, as well as the underlying mechanisms. GalR1 CRISPR and GalR1 selective agonist, M617, was administered, respectively. Extracellular-signal-regulated kinase (ERK) inhibitor (U0126) and glycogen synthase kinase 3-beta (GSK3-β) CRISPR were administered to investigate the involvement of the ERK/GSK3-β pathway in GalR1-mediated neuroprotection after SAH. Outcome assessments included neurobehavioral tests, western blot, and immunohistochemistry. The results showed that endogenous ligand galanin (Gal) and GalR1 were markedly increased in the ipsilateral brain hemisphere at 12 h and 24 h after SAH. GalR1 were expressed mainly in neurons, but expression was also observed in some astrocytes and microglia. GalR1 CRISPR knockdown exacerbated neurological deficits and neuronal apoptosis 24 h after SAH. Moreover, activation of GalR1 with M617 significantly improved short- and long-term neurological deficits but decreased neuronal apoptosis after SAH. Furthermore, GalR1 activation dysregulated the protein levels of phosphorylated ERK and GSK-3β, but downregulated the phosphorylated Tat-interactive protein 60 (TIP60) and cleaved caspase-3 at 24 h after SAH. GalR1 CRISPR, U0126, and GSK-3β CRISPR abolished the beneficial effects of GalR1 activation at 24 h after SAH in rats. Collectively, the present study demonstrated that activation of GalR1 using M617 attenuated neuronal apoptosis through the ERK/GSK-3β/TIP60 pathway after SAH in rats. GalR1 may serve as a promising therapeutic target for SAH patients.
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http://dx.doi.org/10.1007/s13311-021-01066-xDOI Listing
June 2021

Relationship between the position of the maxillary incisor and upper lip.

Authors:
Tao Shen Hui Shi

Am J Orthod Dentofacial Orthop 2021 06;159(6):705

Nanchang, Jiangxi, China.

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http://dx.doi.org/10.1016/j.ajodo.2021.03.004DOI Listing
June 2021

Structure-Based Design of Highly Potent Toll-like Receptor 7/8 Dual Agonists for Cancer Immunotherapy.

J Med Chem 2021 06 28;64(11):7507-7532. Epub 2021 May 28.

School of Pharmaceutical Sciences, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Beijing Advanced Innovation Center for Human Brain Protection, Tsinghua University, Beijing 100084, China.

Activation of the toll-like receptors 7 and 8 has emerged as a promising strategy for cancer immunotherapy. Herein, we report the design and synthesis of a series of pyrido[3,2-]pyrimidine-based toll-like receptor 7/8 dual agonists that exhibited potent and near-equivalent agonistic activities toward TLR7 and TLR8. In vitro, compounds and significantly induced the secretion of IFN-α, IFN-γ, TNF-α, IL-1β, IL-12p40, and IP-10 in human peripheral blood mononuclear cell assays. In vivo, compounds , , and significantly suppressed tumor growth in CT26 tumor-bearing mice by remodeling the tumor microenvironment. Additionally, compounds , , and markedly improved the antitumor activity of PD-1/PD-L1 blockade. In particular, compound combined with the anti-PD-L1 antibody led to complete tumor regression. These results demonstrated that TLR7/8 agonists (, , and ) held great potential as single agents or in combination with PD-1/PD-L1 blockade for cancer immunotherapy.
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http://dx.doi.org/10.1021/acs.jmedchem.1c00179DOI Listing
June 2021

Astragaloside IV prevents acute myocardial infarction by inhibiting the TLR4/MyD88/NF-κB signaling pathway.

J Food Biochem 2021 07 25;45(7):e13757. Epub 2021 May 25.

School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, P.R. China.

Although astragaloside IV protects from acute myocardial infarction (AMI)-induced chronic heart failure (CHF), the underlying mechanism of action is unclear. We determined the potential therapeutic effect of astragaloside IV using molecular docking approaches and validated the findings by the ligation of the left anterior descending (LAD) coronary artery-induced AMI rat model. The interaction between astragaloside IV and myeloid differentiation factor 88 (MyD88) was evaluated by SwissDock. To explore the mechanisms underlying the beneficial effects of astragaloside IV in the LAD coronary artery ligation-induced AMI model, we administered the rats with astragaloside IV for 4 weeks. Hemodynamic indexes were used to evaluate the degree of myocardial injury in model rats. The histopathological changes in myocardium were detected by hematoxylin & eosin (H&E) staining and Masson's staining. Myocardium homogenate contents of collagen I and collagen III were evaluated by ELISA. The level of myocardial hydroxyproline (HYP) was determined by alkaline hydrolysis. Immunohistochemistry was used to examine collagen I. Western blotting was used to examine relevant proteins. As per the molecular docking study results, astragaloside IV may act on MyD88. Furthermore, astragaloside IV improved hemodynamic disorders, alleviated pathological changes, and reduced abnormal collagen deposition and myocardial HYP in vivo. Astragaloside IV significantly reduced the overexpression of TLR4, MyD88, NF-Κb, and TGF-β, which further validated the molecular docking findings. Hence, astragaloside IV ameliorates AMI by reducing inflammation and blocking TLR4/MyD88/NF-κB signaling. These results indicate that astragaloside IV may alleviate AMI. PRACTICAL APPLICATIONS: Astragaloside IV, a small active substance extracted from Astragalus membranaceus, has demonstrated potent protective effects against cardiovascular ischemia/reperfusion, diabetic nephropathy, and other diseases. Molecular docking experiments showed that astragaloside IV might act on the myeloid differentiation factor 88 (MyD88). Astragaloside IV can effectively reduce the overexpression of TLR4, MyD88, and NF-κB p65, indicating that astragaloside IV inhibits inflammation via TLR4/MyD88/NF-κB signaling pathway. These results indicate that astragaloside IV may alleviate acute myocardial infarction.
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http://dx.doi.org/10.1111/jfbc.13757DOI Listing
July 2021

Pyruvate Kinase M2 Contributes to TLR-Mediated Inflammation and Autoimmunity by Promoting Pyk2 Activation.

Front Immunol 2021 7;12:680068. Epub 2021 May 7.

Institute of Immunology and Molecular Medicine, Jining Medical University, Jining, China.

Toll-like receptors (TLRs) play critical roles in regulating the abnormal activation of the immune cells resulting in the pathogenesis of inflammation and autoimmune diseases. Pyruvate kinase M2 (PKM2), which governs the last step of glycolysis, is involved in multiple cellular processes and pathological conditions. However, little is known about the involvement of PKM2 in regulating TLR-mediated inflammation and autoimmunity. Herein, we investigated the role of PKM2 in the activation of the TLR pathways and the pathogenesis of inflammation and autoimmune diseases. The activation of TLR4, TLR7 and TLR9 pathways was found to induce the up-regulation of PKM2 expression in macrophages, dendritic cells (DCs) and B cells. The over-expression of PKM2 promotes the activation of TLR4, TLR7 and TLR9 pathways while interference with the PKM2 expression or the addition of the PKM2 inhibitor (PKM-IN) markedly inhibited the activation of TLR4, TLR7 and TLR9 pathways. Mechanistically, PKM2 augmented the activation of TLR4, TLR7 and TLR9 pathways by promoting the activation of the proline-rich tyrosine kinase 2 (Pyk2). Intriguingly, the PKM2 inhibitor PKM2-IN significantly protected the mice from the endotoxic shock mediated by the TLR4-agonist LPS. Additionally, it alleviated the progression in the TLR7-agonist imiquimod-mediated lupus mice and spontaneous lupus MRL/ mice. Moreover, PKM2 expression was highly elevated in the monocytes, DCs and B cells from systemic lupus erythematous (SLE) patients compared with those from the healthy donors. Besides, the PKM2 expression level was positively correlated with the degree of activation of these immune cells. In summary, PKM2 contributed to TLR-mediated inflammation and autoimmunity and can be a valuable target to control inflammation and autoimmunity.
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http://dx.doi.org/10.3389/fimmu.2021.680068DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138060PMC
May 2021

Rcl1 depletion impairs 18S pre-rRNA processing at the A1-site and up-regulates a cohort of ribosome biogenesis genes in zebrafish.

Nucleic Acids Res 2021 06;49(10):5743-5759

MOE Key Laboratory for Molecular Animal Nutrition, College of Animal Sciences, China.

Yeast Rcl1 is a potential endonuclease that mediates pre-RNA cleavage at the A2-site to separate 18S rRNA from 5.8S and 25S rRNAs. However, the biological function of Rcl1 in opisthokonta is poorly defined. Moreover, there is no information regarding the exact positions of 18S pre-rRNA processing in zebrafish. Here, we report that zebrafish pre-rRNA harbours three major cleavage sites in the 5'ETS, namely -477nt (A'-site), -97nt (A0-site) and the 5'ETS and 18S rRNA link (A1-site), as well as two major cleavage regions within the ITS1, namely 208-218nt (site 2) and 20-33nt (site E). We also demonstrate that depletion of zebrafish Rcl1 mainly impairs cleavage at the A1-site. Phenotypically, rcl1-/- mutants exhibit a small liver and exocrine pancreas and die before 15 days post-fertilization. RNA-seq analysis revealed that the most significant event in rcl1-/- mutants is the up-regulated expression of a cohort of genes related to ribosome biogenesis and tRNA production. Our data demonstrate that Rcl1 is essential for 18S rRNA maturation at the A1-site and for digestive organogenesis in zebrafish. Rcl1 deficiency, similar to deficiencies in other ribosome biogenesis factors, might trigger a common mechanism to upregulate the expression of genes responsible for ribosome biogenesis.
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http://dx.doi.org/10.1093/nar/gkab381DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8191805PMC
June 2021

Characteristics of purified Anti-β2GPI IgG N-glycosylation associate with thrombotic, obstetric, and catastrophic antiphospholipid syndrome.

Rheumatology (Oxford) 2021 May 20. Epub 2021 May 20.

Department of Rheumatology and Immunology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, No. 197 Ruijin Second Road, Shanghai, 200025, China.

Objective: Anti-β-2 glycoprotein I (anti-β2GPI) antibodies, defined as primary pathogenic antibody in antiphospholipid syndrome (APS). It has been reported that IgG Fc N-glycosylation affects IgG effector, we aim to investigate the association of Fc glycosylation profiles of purified anti-β2GP1 IgG with clinical features of APS.

Methods: We purify anti-β2GPI IgG and total IgG from 82 APS patients including 9 catastrophic antiphospholipid syndrome (CAPS) patients, as well as total IgG from 103 healthy controls to quantitatively analyze all detectable Fc N-glycanforms of all IgG subclasses with Multiple Reaction Monitoring (MRM) method based on UPLC-ESI-QqQ mass spectrometry.

Results: Both purified anti-β2GPI IgG and APS total IgG showed altered N-glycan profiles when compared with HC IgG. Anti-β2GPI IgG presented with lower galactosylation, increased bisection and core fucosylation compared with APS total IgG and HC IgG. We found higher galactosylation of aβ2GPI IgG2 in thrombotic APS compared with the obstetric APS, and lower galactosylation of aβ2GPI IgG2 associated with late pregnancy morbidity. Moreover, low galactosylation of all anti-β2GPI IgG subclasses, increased bisection and core fucosylation of anti-β2GPI IgG1/2 were strongly associated with CAPS and triple positivity of antiphospholipid antibodies (aPLs).

Conclusion: We comprehensively characterize the N-Glycans landscape of both anti-β2GP1 and total IgG in APS. Altered N-glycan profiles of anti-β2GPI IgG enables enabled the antibodies with proinflammatory properties. Furthermore, we associated levels of IgG Fc-glycosylation with clinical features antiphospholipid syndrome. These findings could increase our understanding of anti-β2GPI antibody mediated mechanisms in APS and be used to develop diagnostics and new target treatments.
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http://dx.doi.org/10.1093/rheumatology/keab416DOI Listing
May 2021

Venlafaxine vs. fluoxetine in postmenopausal women with major depressive disorder: an 8-week, randomized, single-blind, active-controlled study.

BMC Psychiatry 2021 05 19;21(1):260. Epub 2021 May 19.

The National Clinical Research Center for Mental Disorders & Beijing Key Laboratory of Mental Disorders & Beijing Anding Hospital, Capital Medical University, No 5. Ankang Lane, Deshengmen Wai, Xicheng District, Beijing, 100088, China.

Background: In the population of postmenopausal patients with major depressive disorder (MDD), the superiority of serotonin-norepinephrine reuptake inhibitors (SNRIs) over selective serotonin reuptake inhibitors (SSRIs) has not yet been definitively proven. Consequently, a direct comparison of the efficacy of SSRIs and SNRIs in the treatment of postmenopausal depression could provide relevant data. The aim of this study was to compare the efficacy and safety of venlafaxine vs. fluoxetine in the treatment of postmenopausal MDD.

Methods: This was an 8-week, multicenter, randomized, single-blind, active-controlled trial conducted at a psychiatric hospital (Beijing Anding Hospital) and a general hospital (Beijing Chaoyang Hospital) between April 2013 and September 2017. The primary outcome measure was improving depressive symptoms (Hamilton Depression Rating Scale (HAMD-24) score). The secondary outcomes included the change of HAMD-24 anxiety/somatization factor score and Clinical Global Impressions-Improvement (CGI-I) response rate. Safety was assessed by treatment-emergent adverse events (TEAEs) and laboratory tests. Efficacy was analyzed by using the full analysis set (FAS) following the modified intention-to-treat (mITT) principle. The primary endpoint measurements were analyzed using a mixed-effect model for repeated measures (MMRM) model with patients as a random-effect factor, treatment group as the independent variable, time as a repeated measure, and baseline covariates, using a first-order ante dependence covariance matrix.

Results: A total of 184 women were randomized. The full analysis set (FAS) included 172 patients (venlafaxine, n = 82; fluoxetine, n = 90). Over the 8-week study period, the reduction in HAMD-24 scores was significant (P < 0.001) in both groups, while a significantly greater decline from baseline was observed in the venlafaxine group compared with the fluoxetine group (least-squares mean difference [95% CI]: - 2.22 [- 7.08, - 0.41]), P = 0.001). The baseline-to-week-8 least-squares mean change of the anxiety/somatization factor scores, CGI-I response rate were greater in the venlafaxine group than in the fluoxetine group (all P < 0.05). The most frequent TEAEs (≥5%) in both groups were nausea, somnolence, dizziness, headache, and dry mouth. There was no significant difference in the incidence of adverse events between the two groups.

Conclusion: Venlafaxine was well tolerated and compared to fluoxetine, it led to a greater improvement in the treatment of postmenopausal MDD.

Trial Registration: Clinical Trials. gov #NCT01824433 . The trial was registered on April 4, 2013.
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http://dx.doi.org/10.1186/s12888-021-03253-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8135153PMC
May 2021

Understanding the roles of N-methyladenosine writers, readers and erasers in breast cancer.

Neoplasia 2021 Jun 14;23(6):551-560. Epub 2021 May 14.

Institute of Immunology and Molecular Medicine, Jining Medical University, Shandong, China. Electronic address:

Breast cancer is believed to be driven by epigenetic regulation of genes implicated in cell proliferation, survival, and differentiation. Recently, aberrant N-methyladenosine (mA) decorations turned up as crucial epigenetic regulator for malignant breast cancer, which may serve as new targets for breast cancer treatment. Here we briefly outline the functions of mA and its regulatory proteins, including mA "writers," "readers," and "erasers" on RNA life fate, recapitulate the latest breakthroughs in understanding mA modification and its regulatory proteins, and the underlying molecular mechanisms that contribute to the carcinogenesis and the progression of breast cancer, so as to provide potential epigenetic targets for diagnosis, treatment and prognosis in breast cancer.
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http://dx.doi.org/10.1016/j.neo.2021.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138681PMC
June 2021

Src family kinases involved in the differentiation of human preadipocytes.

Mol Cell Endocrinol 2021 08 14;533:111323. Epub 2021 May 14.

Nanjing Maternal and Child Health Medical Institute, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu 210004, China. Electronic address:

Background: Obesity is characterized by the excess accumulation of white adipose tissue (WAT). Src family kinases (SFKs) are non-receptor tyrosine kinases consisting of eight members (SRC, FYN, YES1, HCK, LCK, LYN, FGR and BLK) that have been studied extensively in mammalian cells. Although individual members in murine cells provide some clues that are associated with the regulation of adipogenesis, the specific role of this family in adipocyte differentiation has rarely been assessed, especially in human adipocytes.

Methods: Herein, we first explored the expression profiles of SFKs during human preadipocyte differentiation. Then, we used the pyrazolo-pyrimidinyl-amine compound PP1, a potent SFK inhibitor, to evaluate the function of SFKs during adipocyte differentiation. Furthermore, we adopted a loss-of-function strategy with siRNAs to determine the role of FGR in adipocyte differentiation.

Results: Here, we found that SRC, FYN, YES1, LYN and FGR were expressed in human preadipocytes and induced after the initiation of differentiation. Furthermore, the SFK inhibitor PP1 suppressed adipocyte differentiation. We also found that PP1 significantly suppressed the SFK activity in preadipocytes and decreased the expression of adipogenic genes in early and late differentiation. Given that FGR exhibited the most expression enhancement in mature adipocytes, we focused on FGR and found that its knockdown reduced lipid accumulation and adipogenic gene expression.

Conclusions: Collectively, these findings suggest that SFKs, especially FGR, are involved in the differentiation of human preadipocytes. Our results lay a foundation for further understanding the role of SFKs in adipocyte differentiation and provide new clues for anti-obesity therapies.
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http://dx.doi.org/10.1016/j.mce.2021.111323DOI Listing
August 2021

Serum metabolomic profiling reveals an increase in homocitrulline in Chinese patients with nonalcoholic fatty liver disease: a retrospective study.

PeerJ 2021 3;9:e11346. Epub 2021 May 3.

Department of Gastroenterology and Hepatology, Jinling Hospital, the First School of Clinical Medicine, Southern Medical University, Nanjing, Jiangsu, China.

Backgrounds: Nonalcoholic fatty liver disease (NAFLD) has multiple causes, is triggered by individual genetic susceptibility, environmental factors, and metabolic disturbances, and may be triggered by acquired metabolic stress. The metabolic profiles of NAFLD show significant ethnic differences, and the metabolic characteristics of NAFLD in Chinese individuals are unclear. Our study aimed to identify the metabolites and pathways associated with NAFLD in a Chinese cohort.

Methods: One hundred participants, including 50 NAFLD patients and 50 healthy controls, were enrolled in this retrospective observational study at Jinling Hospital in Nanjing; serum samples were collected from the patients and healthy subjects. The metabolome was determined in all samples by liquid chromatography-hybrid quadrupole time-of-flight mass spectrometry (LC-Q/TOF-MS). Univariate and multivariate statistical analyses were used to compare the metabolic profiles between the two groups.

Results: The comparison indicated that the levels of 89 metabolites were different between the two groups. The glycerophospholipid family of metabolites was the most abundant family of metabolites that demonstrated significant differences. L-acetylcarnitine, L-homocitrulline, and glutamic acid were the top three metabolites ranked by VIP score and had favorable effective functions for diagnosis. Moreover, pathway enrichment analysis suggested 14 potentially different metabolic pathways between NAFLD patients and healthy controls based on their impact value. Biological modules involved in the lipid and carbohydrate metabolism had the highest relevance to the conditions of NAFLD. Glycerophospholipid metabolism had the strongest associations with the conditions of NAFLD.

Conclusions: Our data suggest that the serum metabolic profiles of NAFLD patients and healthy controls are different. L-Homocitrulline was remarkably increased in NAFLD patients.
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http://dx.doi.org/10.7717/peerj.11346DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8101472PMC
May 2021

Identification of compounds with antipyretic effects and anti-endotoxin activity in different species of using spectrum-effect correlation.

Exp Ther Med 2021 Jul 22;22(1):665. Epub 2021 Apr 22.

School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550025, P.R. China.

Liquid chromatography (LC) is a common and straight forward approach used in the evaluation of the quality of Traditional Chinese Medicines (TCMs). Quality control is a critical step when systematically assessing the efficacy of TCMs. In the present study, the spectrum-effect correlation method was used to identify pharmacologically active substances. The aim of the present study was to investigate the underlying correlations between common chemical compounds with antipyretic effects and the anti-endotoxin activity of . The common chemical constituents of were analyzed using LC, and the antipyretic effects and anti-endotoxin activity were determined using ELISAs. Combining the results of bivariate and principal component analysis methods, eight active constituents were qualitatively and quantitatively analyzed. The results of these analyses indicated that neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid and isochlorogenic acids A, B and C served a synergistic role with respect to antipyretic effects and anti-endotoxin activity. The present study lays a foundation for the future clinical use of .
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http://dx.doi.org/10.3892/etm.2021.10097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8112112PMC
July 2021

Conducting polymer hydrogels as a sustainable platform for advanced energy, biomedical and environmental applications.

Sci Total Environ 2021 Sep 30;786:147430. Epub 2021 Apr 30.

Key Laboratory of Jiangxi Province for Persistent Pollutants Control and Resources Recycle, Nanchang Hangkong University, Nanchang 330063, PR China; National-Local Joint Engineering Research Center of Heavy Metals Pollutants Control and Resource Utilization, Nanchang Hangkong University, Nanchang 330063, PR China. Electronic address:

Environmentally friendly polymeric materials and derivative technologies play increasingly important roles in the sustainable development of our modern society. Conducting polymer hydrogels (CPHs) synergizing the advantageous characteristics of conventional hydrogels and conducting polymers are promising to satisfy the requirements of environmental sustainability. Beyond their use in energy and biomedical applications that require exceptional mechanical and electrical properties, CPHs are emerging as promising contaminant adsorbents owing to their porous network structure and regulable functional groups. Here, we review the currently available strategies for synthesizing CPHs, focusing primarily on multifunctional applications in energy storage/conversion, biomedical engineering and environmental remediation, and discuss future perspectives and challenges for CPHs in terms of their synthesis and applications. It is envisioned to stimulate new thinking and innovation in the development of next-generation sustainable materials.
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http://dx.doi.org/10.1016/j.scitotenv.2021.147430DOI Listing
September 2021

Role of the ionic environment in enhancing the activity of reacting molecules in zeolite pores.

Science 2021 05 6;372(6545):952-957. Epub 2021 May 6.

Department of Chemistry and Catalysis Research Center, Technical University of Munich, Lichtenbergstrasse 4, 85747 Garching, Germany.

Tailoring the molecular environment around catalytically active sites allows for the enhancement of catalytic reactivity through a hitherto unexplored pathway. In zeolites, the presence of water creates an ionic environment via the formation of hydrated hydronium ions and the negatively charged framework aluminum tetrahedra. The high density of cation-anion pairs determined by the aluminum concentration of a zeolite induces a high local ionic strength that increases the excess chemical potential of sorbed and uncharged organic reactants. Charged transition states (carbocations for example) are stabilized, which reduces the energy barrier and leads to higher reaction rates. Using the intramolecular dehydration of cyclohexanol on H-MFI zeolites in water, we quantitatively show an enhancement of the reaction rate by the presence of high ionic strength as well as show potential limitations of this strategy.
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http://dx.doi.org/10.1126/science.abh3418DOI Listing
May 2021

LncRNA NONMMUT055714 acts as the sponge of microRNA-7684-5p to protect against postoperative cognitive dysfunction.

Aging (Albany NY) 2021 04 26;13(9):12552-12564. Epub 2021 Apr 26.

Department of Anesthesiology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China.

Postoperative cognitive dysfunction (POCD) is a neurological complication of surgery especially common in elderly patients. In this study, we investigated the role of NONMMUT055714 in POCD via regulation of miR-7684-5p. In a POCD mouse model, we induced overexpression of NONMUTT055714 via transfection of lentivrus into the hippocampus, and used the Morris water maze for assessment of cognitive function. Silencing of NONMUTT055714 and miR-7684-5p was induced in primary hippocampal neurons to observe the effects of these regulatory RNAs on cellular processes. Bioinformatics analysis and a double luciferase reporter experiment were performed to further explore the relationship between NONMMUT055714, miR-7684-5p, and SORLA. Cell and animal rescue experiments were performed to verify the ability of miR-7684-5p to reverse the protective effects of NONMMUT055714 overexpression in POCD. We observed that NONMMUT055714 has decreased expression in the POCD mouse model. Overexpression of NONMMUT055714 protected against cognitive impairment of the POCD mouse model . We identified miR-7684-5p as a NONMMUT055714-related miRNA and in turn as an upstream regulator of SORLA. We found that NONMMUT055714 downregulation is associated with decreased SORLA, increased Aβ and p-tau expression, increased inflammatory biomarkers, increased markers of oxidative stress, and increased neuronal apoptosis . The effects of NONMMUT055714 downregulation were reversed by silencing miR-7684-5p and . Taken together, our findings suggest that NONMMUT055714 is protective against the development of POCD via its function as a ceRNA (or miRNA sponge) in the regulation of miR-7684-5p and SORLA. We therefore propose NONMMUT055714 as a novel target for the investigation and prevention of POCD.
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http://dx.doi.org/10.18632/aging.202932DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8148455PMC
April 2021

Self-Adhesion Conductive Sub-micron Fiber Cardiac Patch from Shape Memory Polymers to Promote Electrical Signal Transduction Function.

ACS Appl Mater Interfaces 2021 May 26;13(17):19593-19602. Epub 2021 Apr 26.

College of Textile Science and Engineering, Zhejiang Sci-Tech University, No. 928, 2nd Street, Xiasha Higher Education Zone, Hangzhou 310018, China.

Myocardial infarction (MI) constitutes the first cause of morbidity and mortality in our life, so using highly conductive and elastic materials to produce an engineered cardiac patch is an effective way to improve the myocardium infarction area function. Here, shape memory polymers of the polyurethane/polyaniline/silicon oxide (PU/PANI/SiO) electrospinning sub-micron fiber patch were precisely produced in the case of the hydrogen bonding effect and interaction between the carboxyl groups to provide compatibility, phase mixing/miscibility, and stability. The sub-micron fiber patch prepared by our group has some remarkable characteristics, such as sub-micron fibers, 3D porous structure, special thickness to simulate the extracellular matrix (ECM), elastic deformation, good properties in conducting weak electrical signals, stability to maintain the whole structure, and self-adhesion. This sub-micron fiber material has been proven to be effective, easy, and reliable. Through precise design of the material system, structure regulation, and performance optimization, the aim is to produce a sub-micron fiber cardiac patch to simulate the myocardium ECM and improve conductive signal transduction for potential MI therapy.
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http://dx.doi.org/10.1021/acsami.0c22844DOI Listing
May 2021

A MnO nanosheet-mediated photo-controlled DNAzyme for intracellular miRNA cleavage to suppress cell growth.

Analyst 2021 May 20;146(10):3391-3398. Epub 2021 Apr 20.

State Key Laboratory of Chemo/Biosensing and Chemometrics, College of Chemistry and Chemical Engineering, Key Laboratory for Bio-Nanotechnology and Molecular Engineering of Hunan Province, Hunan University, Changsha, P. R. China.

Certain miRNAs, called oncomiRs, play a causal role in the onset and maintenance of cancer when overexpressed, thus, representing a potential new class of targets for therapeutic intervention. RNA-cleaving DNAzymes, mainly aimed at mRNA, have shown potential as therapeutic agents for various diseases. However, it's rarely reported that a DNAzyme was used for intracellular miRNA cleavage to suppress cell growth. Herein, we have developed a MnO nanosheet-mediated photo-controlled DNAzyme (NPD) for intracellular miRNA cleavage to suppress cell growth. MnO nanosheets adsorb photocaged DNAzymes, protect them from enzymatic digestion, and efficiently deliver them into cells. In the presence of intracellular glutathione (GSH), MnO nanosheets are reduced to Mn ions, which serve as cofactors of the 8-17 DNAzyme for miRNA cleavage. Once the DNAzyme is activated by light, it can cyclically cleave endogenous miR-21 inside cells, which would suppress cancer cell migration and invasion, and finally induce cancer cell apoptosis.
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http://dx.doi.org/10.1039/d1an00406aDOI Listing
May 2021

Autoantibodies stabilize neutrophil extracellular traps in COVID-19.

medRxiv 2021 Apr 5. Epub 2021 Apr 5.

The release of neutrophil extracellular traps ( ) by hyperactive neutrophils is recognized to play an important role in the thromboinflammatory milieu inherent to severe presentations of COVID-19. At the same time, a variety of functional autoantibodies have been observed in individuals with severe COVID-19 where they likely contribute to immunopathology. Here, we aimed to determine the extent to which autoantibodies might target NETs in COVID-19 and, if detected, to elucidate their potential functions and clinical associations. We measured global anti-NET activity in 171 individuals hospitalized with COVID-19 alongside 48 healthy controls. We found high anti-NET activity in the IgG and IgM fractions of approximately 40% and 50% of patients, respectively. There was a strong correlation between anti-NET IgG and anti-NET IgM, with high anti-NET antibody levels in general associating with circulating markers of NETs such as myeloperoxidase-DNA complexes and calprotectin. Clinically, anti-NET antibodies tracked with impaired oxygenation efficiency and elevated levels of circulating D-dimer. Furthermore, patients who required mechanical ventilation had higher levels of anti-NET antibodies than those who did not require oxygen supplementation. Mechanistically, anti-NET antibodies of the IgG isotype impaired the ability of DNases in healthy serum to degrade NETs. In summary, these data reveal high levels of anti-NET antibodies in individuals hospitalized with COVID-19, where they likely impair NET clearance and thereby potentiate SARS-CoV-2 mediated thromboinflammation.
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http://dx.doi.org/10.1101/2021.03.31.21254692DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8043486PMC
April 2021

In vivo genome editing in mouse restores dystrophin expression in Duchenne muscular dystrophy patient muscle fibers.

Genome Med 2021 Apr 12;13(1):57. Epub 2021 Apr 12.

CAS Key Laboratory of Regenerative Biology, Guangdong Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510530, China.

Background: Mutations in the DMD gene encoding dystrophin-a critical structural element in muscle cells-cause Duchenne muscular dystrophy (DMD), which is the most common fatal genetic disease. Clustered regularly interspaced short palindromic repeat (CRISPR)-mediated gene editing is a promising strategy for permanently curing DMD.

Methods: In this study, we developed a novel strategy for reframing DMD mutations via CRISPR-mediated large-scale excision of exons 46-54. We compared this approach with other DMD rescue strategies by using DMD patient-derived primary muscle-derived stem cells (DMD-MDSCs). Furthermore, a patient-derived xenograft (PDX) DMD mouse model was established by transplanting DMD-MDSCs into immunodeficient mice. CRISPR gene editing components were intramuscularly delivered into the mouse model by adeno-associated virus vectors.

Results: Results demonstrated that the large-scale excision of mutant DMD exons showed high efficiency in restoring dystrophin protein expression. We also confirmed that CRISPR from Prevotella and Francisella 1(Cas12a)-mediated genome editing could correct DMD mutation with the same efficiency as CRISPR-associated protein 9 (Cas9). In addition, more than 10% human DMD muscle fibers expressed dystrophin in the PDX DMD mouse model after treated by the large-scale excision strategies. The restored dystrophin in vivo was functional as demonstrated by the expression of the dystrophin glycoprotein complex member β-dystroglycan.

Conclusions: We demonstrated that the clinically relevant CRISPR/Cas9 could restore dystrophin in human muscle cells in vivo in the PDX DMD mouse model. This study demonstrated an approach for the application of gene therapy to other genetic diseases.
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http://dx.doi.org/10.1186/s13073-021-00876-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8042958PMC
April 2021

3,3'-Diindolylmethane Promotes Gastric Cancer Progression β-TrCP-Mediated NF-κB Activation in Gastric Cancer-Derived MSCs.

Front Oncol 2021 24;11:603533. Epub 2021 Mar 24.

Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, Institute of Stem Cell, School of Medicine, Jiangsu University, Zhenjiang, China.

Gastric cancer is a malignant tumor characterized by high morbidity and invasion. Surgery combined with chemo-radiotherapy is the most common treatment for gastric cancer, while multiple drug resistance always results in treatment failure. Once the anti-tumor drugs enter the tumor foci, tumor cells as well as those found in the microenvironment are affected. However, the effects of drugs on tumor microenvironment (TME) are easily overlooked. In this study, we investigated the effects of the anti-cancer drug 3,3'-diindolylmethane (DIM) on gastric cancer-derived mesenchymal stem cells (GC-MSCs) and their subsequent impact on cancer progression. Surprisingly, we found that the therapeutic concentration of DIM upregulated the expression level of tumor-related factors such as CCL-2, IL-6, and IL-8 in GC-MSCs. The conditioned medium of DIM-treated GC-MSCs promoted the proliferation, invasion, and migration of gastric cancer cells and tumor growth . Mechanistically, DIM enhanced the expression of β-TrCP, an E3 ubiquitin ligase leading to IκBα degradation and NF-κB activation in GC-MSCs. The β-TrCP knockdown partially eliminated positive results caused by DIM. Our results showed that the therapeutic dosage of DIM induced cell death in cancer cells, while enhancing MSC paracrine functions in the stroma to offset the original DIM effect on cancer cells. These findings provide a new mechanism of anti-cancer drug resistance and remind us to adjust the chemotherapeutic scheme by combining the anti-cancer drug with an appropriate signaling pathway inhibitor to block the side effects of drug on targeted TME cells.
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http://dx.doi.org/10.3389/fonc.2021.603533DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8024625PMC
March 2021

Platelet-rich plasma promotes MSCs exosomes paracrine to repair acute kidney injury via AKT/Rab27 pathway.

Am J Transl Res 2021 15;13(3):1445-1457. Epub 2021 Mar 15.

Zhenjiang Key Laboratory of High Technology Research on Exosomes Foundation and Transformation Application, Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University Zhenjiang 212013, Jiangsu, China.

Acute kidney injury (AKI) is defined by rapid deterioration of renal function, and is a common complication in hospitalized patients. Among the recent therapeutic options, mesenchymal stem cells (MSCs) are considered a promising therapeutic strategy for damaged tissue repair. Platelet rich plasma (PRP) regulates mesenchymal cells to repair tissue damage through the release of growth factors. In this study, we proposed a possible therapeutic use of MSCs stimulated by platelet-rich plasma (PRP-MSCs) in a glycerin-induced AKI murine model. and studies, showed that PRP-MSCs could significantly attenuate serum blood urea nitrogen and creatinine levels, and reverse the histopathological kidney damage. PRP-MSCs treatment reduced renal tubular cell apoptosis stimulated by glycerin. We confirmed that PRP promoted the proliferation and reinforced the stemness of MSCs by inducing YAP nucleus expression, and that PRP promoted MSCs exosomes in a paracrine manner to repair AKI through an activated AKT/Rab27 pathway. Our results revealed that the PRP stimulated MSCs paracrine pathway could effectively alleviate glycerin-induced AKI. Therefore, PRP pretreatment may be a new method to improve the therapeutic effect of MSCs.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014389PMC
March 2021
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