Publications by authors named "Xiao Zhang"

2,651 Publications

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Atractylodin attenuates the expression of MUC5AC and extracellular matrix in lipopolysaccharide-induced airway inflammation by inhibiting the NF-κB pathway.

Environ Toxicol 2021 Jun 21. Epub 2021 Jun 21.

Department of Respiratory and Critical Care Medicine, The Second People's Hospital of Huai'an, The Affiliated Huai'an Hospital of Xuzhou Medical University, Huai'an, China.

This study aimed to explore the effects of atractylodin (ATR) on lipopolysaccharide (LPS)-induced inflammatory response in human airway epithelial cells. The cytotoxicity was assessed by CCK-8 assay. The mRNA expression and concentration of interleukin (IL)-6, IL-8, and mucin 5AC (MUC5AC) were measured by qRT-PCR and ELISA, respectively. Western blotting was performed to determine protein expression. We found that LPS stimulation increased the mRNA expression and concentrations of IL-6, IL-8, and MUC5AC, as well as the expression of Col-I and FN in 16HBE cells, but this effect of LPS was attenuated by ATR treatment. Mechanistically, ATR suppressed LPS-induced activation of the NF-κB pathway in 16HBE cells. Moreover, ATR repressed ovalbumin-induced airway inflammation and NF-kB pathway in mice. In conclusion, ATR attenuated the expression of MUC5AC and ECM in LPS-induced airway inflammation by inhibiting the NF-κB pathway.
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http://dx.doi.org/10.1002/tox.23311DOI Listing
June 2021

Homogeneity or heterogeneity, the paradox of neurovascular pericytes in the brain.

Glia 2021 Jun 21. Epub 2021 Jun 21.

Center for Brain Science of Shanghai Children's Medical Center, Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Pericytes are one of the main components of the neurovascular unit. They play a critical role in regulating blood flow, blood-brain barrier permeability, neuroinflammation, and neuronal activity. In the central nervous system (CNS), pericytes are classified into three subtypes, that is, ensheathing, mesh, and thin-strand pericytes, based on their distinct morphologies and region-specific distributions. However, whether these three types of pericytes exhibit heterogeneity or homogeneity with regard to membrane properties has been understudied to date. Here, we combined bulk RNA sequencing analysis with electrophysiological methods to demonstrate that the three subtypes of pericytes share similar electrical membrane properties in the CNS, suggesting a homogenous population of neurovascular pericytes in the brain. Furthermore, we identified an inwardly rectifying potassium channel subtype Kir4.1 functionally expressed in pericytes. Electrophysiological patch clamp recordings indicate that Kir4.1 channel currents in pericytes represent a small portion of the K macroscopic currents in physiological conditions. However, a significant augmentation of Kir4.1 currents in pericytes was induced when the extracellular K was elevated to pathological levels, suggesting pericytes Kir4.1 channels might play an important role as K sensors and contribute to K homeostasis in local neurovascular networks in pathology.
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http://dx.doi.org/10.1002/glia.24054DOI Listing
June 2021

A longitudinal examination of the relationship between smoking and panic, anxiety, and depression in Chinese and German students.

Addict Behav Rep 2021 Dec 15;14:100347. Epub 2021 Apr 15.

Mental Health Research and Treatment Center, Ruhr-Universität Bochum, Germany.

The present study examines the relationship between smoking and panic, depression, and anxiety over time and across two cultures, using data from the BOOM studies. The relationship between smoking and anxiety disorders, including panic requires further exploration, in order to reconcile inconsistent, contradictory findings and cross-cultural differences. Participants in the present study included 5,416 Chinese university students and 282 German university students. Participants completed surveys assessing smoking, panic, depression, and anxiety. Multiple logistic regressions were used to examine predict later mental health from smoking, as well as later smoking from mental health. In sum, across the regressions, smoking at baseline did not predict higher panic or depression at follow-up in either German or Chinese students. It did predict lower anxiety in German students. Anxiety at baseline, but not depression, predicted increased likelihood of smoking at follow-up in German students. The relationship between smoking and anxiety disorders is one that will require further exploration, in order to reconcile inconsistent, contradictory findings and cross-cultural differences. The present data point to a relationship between anxiety and later smoking, and also to a negative, though small, relationship between smoking and later anxiety in German students, and no prospective relationship in either direction in Chinese students.
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http://dx.doi.org/10.1016/j.abrep.2021.100347DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8193104PMC
December 2021

ApoM is an important potential protective factor in the pathogenesis of primary liver cancer.

J Cancer 2021 4;12(15):4661-4671. Epub 2021 Jun 4.

Anhui Province Key Laboratory of Biological Macro-molecules Research, Wannan Medical College, Wuhu 241002, China.

In recent years, abnormal liver lipid metabolism has emerged as one of the important pathogenesis pathways of primary liver cancer. It is highly important to identify the mechanisms to explore potential prevention and treatment targets. Apolipoprotein M is specifically expressed in the liver and participates in liver lipid metabolism, but the evidence that ApoM affects primary liver cancer is insufficient. The Cancer Genome Atlas (TCGA) database and clinical case analysis, as well as animal level and cell level analysis suggest that the expression level of gene in cancer tissues is lower than that in paracarcinoma tissues. Further experimental research found that the deletion of ApoM significantly increased the proliferation of mouse liver cancer cells (Hepa1-6) and inhibited the level of apoptosis induced by cisplatin. In addition, mouse liver cancer cells lacking ApoM showed stronger migration and invasion capabilities in transwell experiments. In contrast, overexpression of ApoM in Hepa1-6 cells and Huh-7 cells showed an inhibition of proliferation, up-regulation apoptosis and reduced migration and invasion. , the deletion of the accelerated tumorigenesis in nude mice and allowed the mice to develop liver tumor mutations more quickly under the induction of N-nitrosodiethylamine and the survival time of mice was shorter than that control. Therefore, ApoM may be a potential protective factor to inhibit the occurrence and development of primary liver cancer.
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http://dx.doi.org/10.7150/jca.53115DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8210568PMC
June 2021

Correction to: A Hybrid Biofuel and Triboelectric Nanogenerator for Bioenergy Harvesting.

Nanomicro Lett 2020 Apr 16;12(1):92. Epub 2020 Apr 16.

CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 100083, People's Republic of China.

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http://dx.doi.org/10.1007/s40820-020-00433-1DOI Listing
April 2020

Ultra-sensitive Nanoprobe Modified with Tumor Cell Membrane for UCL/MRI/PET Multimodality Precise Imaging of Triple-Negative Breast Cancer.

Nanomicro Lett 2020 Feb 22;12(1):62. Epub 2020 Feb 22.

Department of Nuclear Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, People's Republic of China.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer in which the estrogen receptor and progesterone receptor are not expressed, and human epidermal growth factor receptor 2 is not amplified or overexpressed either, which make the clinical diagnosis and treatment very challenging. Molecular imaging can provide an effective way to diagnose TNBC. Upconversion nanoparticles (UCNPs), are a promising new generation of molecular imaging probes. However, UCNPs still need to be improved for tumor-targeting ability and biocompatibility. This study describes a novel probe based on cancer cell membrane-coated upconversion nanoparticles (CCm-UCNPs), owing to the low immunogenicity and homologous-targeting ability of cancer cell membranes, and modified multifunctional UCNPs. This probe exhibits excellent performance in breast cancer molecular classification and TNBC diagnosis through UCL/MRI/PET tri-modality imaging in vivo. By using this probe, MDA-MB-231 was successfully differentiated between MCF-7 tumor models in vivo. Based on the tumor imaging and molecular classification results, the probe is also expected to be modified for drug delivery in the future, contributing to the treatment of TNBC. The combination of nanoparticles with biomimetic cell membranes has the potential for multiple clinical applications.
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http://dx.doi.org/10.1007/s40820-020-0396-4DOI Listing
February 2020

A Hybrid Biofuel and Triboelectric Nanogenerator for Bioenergy Harvesting.

Nanomicro Lett 2020 Feb 14;12(1):50. Epub 2020 Feb 14.

CAS Center for Excellence in Nanoscience, Beijing Key Laboratory of Micro-Nano Energy and Sensor, Beijing Institute of Nanoenergy and Nanosystems, Chinese Academy of Sciences, Beijing, 100083, People's Republic of China.

Various types of energy exist everywhere around us, and these energies can be harvested from multiple sources to power micro-/nanoelectronic system and even personal electronic products. In this work, we proposed a hybrid energy-harvesting system (HEHS) for potential in vivo applications. The HEHS consisted of a triboelectric nanogenerator and a glucose fuel cell for simultaneously harvesting biomechanical energy and biochemical energy in simulated body fluid. These two energy-harvesting units can work individually as a single power source or work simultaneously as an integrated system. This design strengthened the flexibility of harvesting multiple energies and enhanced corresponding electric output. Compared with any individual device, the integrated HEHS outputs a superimposed current and has a faster charging rate. Using the harvested energy, HEHS can power a calculator or a green light-emitting diode pattern. Considering the widely existed biomechanical energy and glucose molecules in the body, the developed HEHS can be a promising candidate for building in vivo self-powered healthcare monitoring system.
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http://dx.doi.org/10.1007/s40820-020-0376-8DOI Listing
February 2020

A high resolution representation network with multi-path scale for retinal vessel segmentation.

Comput Methods Programs Biomed 2021 Jun 4;208:106206. Epub 2021 Jun 4.

Department of Obstetrics, Zhuhai People's Hospital, Zhuhai Hospital Affiliated with Jinan University, Jinan University, Zhuhai, Guangdong 519000, PR China. Electronic address:

Background And Objectives: Automatic retinal vessel segmentation (RVS) in fundus images is expected to be a vital step in the early image diagnosis of ophthalmologic diseases. However, it is a challenging task to detect the retinal vessel accurately mainly due to the vascular intricacies, lesion areas and optic disc edges in retinal fundus images.

Methods: In this paper, we propose a high resolution representation network with multi-path scale (MPS-Net) for RVS aiming to improve the performance of extracting the retinal blood vessels. In the MPS-Net, there exist one high resolution main road and two lower resolution branch roads where the proposed multi-path scale modules are embedded to enhance the representation ability of network. Besides, in order to guide the network focus on learning the features of hard examples in retinal images, we design a hard-focused cross-entropy loss function.

Results: We evaluate our network structure on DRIVE, STARE, CHASE and synthetic images and the quantitative comparisons with respect to the existing methods are presented. The experimental results show that our approach is superior to most methods in terms of F1-score, sensitivity, G-mean and Matthews correlation coefficient.

Conclusions: The promising segmentation performances reveal that our method has potential in real-world applications and can be exploited for other medical images with further analysis.
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http://dx.doi.org/10.1016/j.cmpb.2021.106206DOI Listing
June 2021

A High Concentration of Abscisic Acid Inhibits Hypocotyl Phototropism in Gossypium arboreum by Reducing the Accumulation and Asymmetric Distribution of Auxin.

J Exp Bot 2021 Jun 18. Epub 2021 Jun 18.

Institute of Plant Stress Biology, State Key Laboratory of Cotton Biology, School of Life Sciences, Henan University, Kaifeng 475004, China.

Hypocotyl phototropism is mediated by the phototropins and plays a critical role in seedling morphogenesis by optimizing growth orientation. However, the mechanisms by which phototropism influences morphogenesis require additional study, especially for polyploid crops such as cotton. Here, we found that hypocotyl phototropism was weaker in G. arboreum than in G. raimondii (two diploid cotton species), and LC-MS analysis indicated that G. arboreum hypocotyls had a higher content of ABA and a lower content of IAA and bioactive GAs. Consistently, the expression of ABA2, AAO3 and GA2OX1 was higher in G. arboreum than in G. raimondii, and that of GA3OX was lower; these changes promoted ABA synthesis and the transformation of active GA to inactive GA. Higher concentrations of ABA inhibited the asymmetric distribution of IAA across the hypocotyl and blocked the phototropic curvature of G. raimondii. Application of IAA or GA3 to the shaded and illuminated sides of the hypocotyl enhanced and inhibited phototropic curvature, respectively, in G. arboreum. The application of IAA but not GA to one side of the hypocotyl caused hypocotyl curvature in the dark. These results indicate that the asymmetric distribution of IAA promotes phototropic growth, and the weakened phototropic curvature of G. arboreum may be attributed to its higher ABA levels that inhibit the action of auxin, which is regulated by GA signaling.
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http://dx.doi.org/10.1093/jxb/erab298DOI Listing
June 2021

Circ_0008542 in osteoblast exosomes promotes osteoclast-induced bone resorption through m6A methylation.

Cell Death Dis 2021 Jun 18;12(7):628. Epub 2021 Jun 18.

Department of Implant Dentistry, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, National Clinical Research Center for Oral Diseases, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, China.

With an increasing aging society, China is the world's fastest growing markets for oral implants. Compared with traditional oral implants, immediate implants cause marginal bone resorption and increase the failure rate of osseointegration, but the mechanism is still unknown. Therefore, it is important to further study mechanisms of tension stimulus on osteoblasts and osteoclasts at the early stage of osseointegration to promote rapid osseointegration around oral implants. The results showed that exosomes containing circ_0008542 from MC3T3-E1 cells with prolonged tensile stimulation promoted osteoclast differentiation and bone resorption. Circ_0008542 upregulated Tnfrsf11a (RANK) gene expression by acting as a miR-185-5p sponge. Meanwhile, the circ_0008542 1916-1992 bp segment exhibited increased m6A methylation levels. Inhibiting the RNA methyltransferase METTL3 or overexpressing the RNA demethylase ALKBH5 reversed osteoclast differentiation and bone resorption induced by circ_0008542. Injection of circ_0008542 + ALKBH5 into the tail vein of mice reversed the same effects in vivo. Site-directed mutagenesis study demonstrated that 1956 bp on circ_0008542 is the m6A functional site with the abovementioned biological functions. In conclusion, the RNA methylase METTL3 acts on the m6A functional site of 1956 bp in circ_0008542, promoting competitive binding of miRNA-185-5p by circ_0008542, and leading to an increase in the target gene RANK and the initiation of osteoclast bone absorption. In contrast, the RNA demethylase ALKBH5 inhibits the binding of circ_0008542 with miRNA-185-5p to correct the bone resorption process. The potential value of this study provides methods to enhance the resistance of immediate implants through use of exosomes releasing ALKBH5.
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http://dx.doi.org/10.1038/s41419-021-03915-1DOI Listing
June 2021

Broadband plasmon-induced transparency modulator in the terahertz band based on multilayer graphene metamaterials.

J Opt Soc Am A Opt Image Sci Vis 2021 Jun;38(6):784-789

In this study, multilayer graphene metamaterials comprising graphene blocks and graphene ribbon are proposed to realize dynamic plasmon-induced transparence (PIT). By changing the position between the graphene blocks, PIT phenomenon will occur in different terahertz bands. Furthermore, PIT with a transparent window width of 1 THz has been realized. In addition, the PIT shows redshifts or blueshifts or disappears altogether upon changing the Fermi level of graphene, and hence a frequency selector from 3.91 to 7.84 THz and an electro-optical switch can be realized. Surprisingly, the group index of this structure can be increased to 469. Compared with the complex and fixed structure of previous studies, our proposed structure is simple and can be dynamically adjusted according to demands, which makes it a valuable platform for ideas to inspire the design of novel electro-optic devices.
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http://dx.doi.org/10.1364/JOSAA.420743DOI Listing
June 2021

Intra- and inter-observer agreements in detecting peri-implant bone defects between periapical radiography and cone beam computed tomography: A clinical study.

J Dent Sci 2021 Jul 14;16(3):948-956. Epub 2020 Nov 14.

Department of Implant Dentistry, Shanghai Ninth People's Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine; National Clinical Research Center for Oral Diseases; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, Shanghai, China.

Background/purpose: Information regarding agreements between periapical radiograph (PA) and cone beam computed tomography (CBCT) in detecting peri-implant defect is still scarce. The aim of this clinical study was to compare agreements between PA and CBCT in detecting peri-implant bone defect.

Materials And Methods: This retrospective clinical study enrolled 32 patients with both PA and CBCT filmed right after implant placement. Four modalities were used for film reading: PA1 (original), PA2 (enhanced brightness/contrast), CBCT1 (selected axial and mesial-distal direction images) and CBCT2 (all data with software). 2 experienced and 2 inexperienced observers scored all films. Intra- and inter-observer agreements were estimated with Cohen's kappa coefficient. Categorized agreements were compared and differences among four modalities were calculated.

Results: Agreements of PA were better than CBCT when detecting peri-implant bone defects in inter-observer agreements (median kappa 0.471 vs. 0.192; p = 0.016). Moreover, agreements in experienced observers were better than inexperienced observers (median kappa 0.883 vs. 0.567; p < 0.001). There was significant difference among four modalities except for experienced observer 2 (p = 0.218).

Conclusion: Agreements of PA are better than CBCT when detecting peri-implant bone defects, especially for inter-observer agreements. Experienced observers are more consistent in assessment than inexperienced ones.
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http://dx.doi.org/10.1016/j.jds.2020.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189872PMC
July 2021

Risk factors and predictive model of adrenocortical insufficiency in patients with traumatic brain injury.

World J Emerg Med 2021 ;12(3):179-184

Department of Emergency, the First Hospital of Shanxi Medical University, Taiyuan 030001, China.

Background: Neuroendocrine dysfunction after traumatic brain injury (TBI) has received increased attention due to its impact on the recovery of neural function. The purpose of this study is to investigate the incidence and risk factors of adrenocortical insufficiency (AI) after TBI to reveal independent predictors and build a prediction model of AI after TBI.

Methods: Enrolled patients were grouped into the AI and non-AI groups. Fourteen preset impact factors were recorded. Patients were regrouped according to each impact factor as a categorical variable. Univariate and multiple logistic regression analyses were performed to screen the related independent risk factors of AI after TBI and develop the predictive model.

Results: A total of 108 patients were recruited, of whom 34 (31.5%) patients had AI. Nine factors (age, Glasgow Coma Scale [GCS] score on admission, mean arterial pressure [MAP], urinary volume, serum sodium level, cerebral hernia, frontal lobe contusion, diffuse axonal injury [DAI], and skull base fracture) were probably related to AI after TBI. Three factors (urinary volume [], serum sodium level [], and DAI []) were independent variables, based on which a prediction model was developed (logit = -3.552+2.583+2.235+2.269).

Conclusions: The incidence of AI after TBI is high. Factors such as age, GCS score, MAP, urinary volume, serum sodium level, cerebral hernia, frontal lobe contusion, DAI, and skull base fracture are probably related to AI after TBI. Urinary volume, serum sodium level, and DAI are the independent predictors of AI after TBI.
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http://dx.doi.org/10.5847/wjem.j.1920-8642.2021.03.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188278PMC
January 2021

New species and records of the subgenus Libnotes (Laosa) Edwards (Diptera, Limoniidae) from China with a key to world species.

Zookeys 2021 1;1041:101-112. Epub 2021 Jun 1.

Key Lab of Integrated Crop Pest Management of Shandong Province, College of Plant Health and Medicine, Qingdao Agricultural University, Qingdao 266109, China Qingdao Agricultural University Qingdao China.

Twenty species of Libnotes (Laosa) Edwards, 1926 are known worldwide and three are known from China so far. Here, two species of are added to the Chinese fauna, of which L. (L.) baiyunensis is described and illustrated as new to science, and L. (L.) fuscinervis Brunetti, 1912 is newly recorded from China. Morphologically, the new species is most similar to L. (L.) charmosyne (Alexander, 1958) but can be distinguished by the pleura of the thorax, the relative position of the additional cross veins in cell r and r, and the details of the male genitalia. A key to the world species of is presented.
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http://dx.doi.org/10.3897/zookeys.1041.65906DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187297PMC
June 2021

N-Myristoylation by NMT1 Is POTEE-Dependent to Stimulate Liver Tumorigenesis Differentially Regulating Ubiquitination of Targets.

Front Oncol 2021 31;11:681366. Epub 2021 May 31.

Department of Clinical Laboratory Medicine, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiaotong University, Shanghai, China.

Background: A tremendous amount of studies have suggested that post-translational modifications (PTMs) play pivotal roles during tumorigenesis. Compared to other PTMs, lipid modification is less studied. Recently, N-myristoylation, one type of lipid modification, has been paid attention to the field of cancer. However, whether and how N-myristoylation exerts its roles in liver tumorigenesis still remains unclear.

Methods: Parallel reaction monitoring (PRM) was conducted to evaluate the expression of protein modification enzymes in paired tissues. Liver conditionally knocking NMT1 out mice model was used to assess the critical roles of N-myristoylation during liver tumorigenesis. Proteomics isobaric tags for relative and absolute quantification (iTraq) was performed to identify proteins that changed while NMT1 was knocked down. The click chemistry assay was used to evaluate the N-myristoylation levels of proteins.

Results: Here, N-myristolyation and its enzyme NMT1, but not NMT2, were found to be critical in liver cancer. Two categories of proteins, i.e., N-myristolyation down-regulated proteins (NDP, including LXN, RPL29, and FAU) and N-myristolyation up-regulated proteins (NUP, including AHSG, ALB, and TF), were revealed negatively and positively regulated by NMT1, respectively. Both NDP and NUP could be N-myristolyated by NMT1 indispensable of POTEE. However, N-myristolyation decreased and increased stability of NDP and NUP, respectively. Mechanistically, NDP-specific binding protein RPL7A facilitated HIST1H4H, which has ubiquitin E3 ligase function, to ubiquitinate NDP. By contrast, NUP-specific binding protein HBB prevented NUP from ubiquitination by HIST1H4H. Notably, function of RPL7A and HBB was all NMT1-dependent. Moreover, NDP suppressed while NUP stimulated transformative phenotypes. Clinically, higher levels of NMT1 and NUP with lower levels of NDP had worse prognostic outcome.

Conclusion: Collectively, N-myristolyation by NMT1 suppresses anti-tumorigenic NDP, whereas it stimulates pro-tumorigenic NUP by interfering their ubiquitination to finally result in a pro-tumorigenic outcome in liver cancer. Targeting N-myristolyation and NMT1 might be helpful to treat liver cancer.
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http://dx.doi.org/10.3389/fonc.2021.681366DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8201403PMC
May 2021

Primitive neuroectodermal tumor of the pericardium: a case report and literature review.

BMC Cardiovasc Disord 2021 Jun 16;21(1):305. Epub 2021 Jun 16.

Department of Radiology, The First Medical Center of Chinese, PLA General Hospital, No.28 Fuxing Street of Haidian District, Beijing, 100853, China.

Background: The primitive neuroectodermal tumors (PNETs) are a family of highly malignant tumors with a multidirectional differential potential. The tumors are characterized by aggressive small round tumor cells that originate from the spinal cord of the central and sympathetic nervous systems. Cases involving the pericardium are extremely rare. Herein, we present a case of peripheral primitive neuroectodermal tumor (pPNET) that originated in the pericardium.

Case Presentation: A 23-year-old woman presented with cough and progressive dyspnea for 1 month, followed by eyelid and facial edema for 10 days, without any apparent cause. Significantly elevated tumor markers were detected in her blood. A cardiac ultrasound revealed a 74 mm × 61 mm spherical mass that was attached to the left pericardium, as well as massive pericardial effusion. Positron emission tomography-CT (PET-CT) showed focal hypermetabolism in the left pericardium. Via histopathology and immunohistochemistry, the spherical mass was identified as PNETS. The patient was successfully treated with a combination of surgical resection via thoracotomy and postoperative chemotherapy, and she was disease-free for 7 years at follow-up. Unfortunately, at 7 years after the treatment, the patient's pPNET recurred. Positron emission tomography-MRI (PET-MRI) and 64-slice coronary CTA revealed that the aorta and multiple coronary arteries were involved. Subsequently, the patient refused a heart transplant and voluntarily left the hospital.

Conclusions: This paper reports on a rare and recurrent case of PNET in the parietal pericardium. With respect to the different biologic characteristics and prognoses of pPNETs (compared to other known pericardium tumors), it is essential to consider this entity as a differential diagnosis in pericardium tumors.
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http://dx.doi.org/10.1186/s12872-021-02113-3DOI Listing
June 2021

Ethanol extract of mulberry leaves partially restores the composition of intestinal microbiota and strengthens liver glycogen fragility in type 2 diabetic rats.

BMC Complement Med Ther 2021 Jun 14;21(1):172. Epub 2021 Jun 14.

Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou Medical University, Xuzhou, 221000, Jiangsu, China.

Background: Mulberry leaf as a traditional Chinese medicine is able to treat obesity, diabetes, and dyslipidemia. It is well known that diabetes leads to intestinal microbiota dysbiosis. It is also recently discovered that liver glycogen structure is impaired in diabetic animals. Since mulberry leaves are able to improve the diabetic conditions through reducing blood glucose level, it would be interesting to investigate whether they have any positive effects on intestinal microbiota and liver glycogen structure.

Methods: In this study, we first determined the bioactive components of ethanol extract of mulberry leaves via high-performance liquid chromatography (HPLC) and liquid chromatography/mass spectrometry (LC/MS). Murine animal models were divided into three groups, normal Sprague-Dawley (SD) rats, high-fat diet (HFD) and streptozotocin (STZ) induced type 2 diabetic rats, and HFD/STZ-induced rats administered with ethanol extract of mulberry leaves (200 mg/kg/day). Composition of intestinal microbiota was analyzed via metagenomics by sequencing the V3-V4 region of 16S rDNAs. Liver glycogen structure was characterized through size exclusion chromatography (SEC). Both Student's t-test and Tukey's test were used for statistical analysis.

Results: A group of type 2 diabetic rat models were successfully established. Intestinal microbiota analysis showed that ethanol extract of mulberry leaves could partially change intestinal microbiota back to normal conditions. In addition, liver glycogen was restored from fragile state to stable state through administration of ethanol extract of mulberry leaves.

Conclusions: This study confirms that the ethanol extract of mulberry leaves (MLE) ameliorates intestinal microbiota dysbiosis and strengthens liver glycogen fragility in diabetic rats. These finding can be helpful in discovering the novel therapeutic targets with the help of further investigations.
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http://dx.doi.org/10.1186/s12906-021-03342-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204513PMC
June 2021

A five-gene signature is a prognostic biomarker in pan-cancer and related with immunologically associated extracellular matrix.

Cancer Med 2021 Jun 14. Epub 2021 Jun 14.

Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory), Guangzhou, China.

The tumor microenvironment (TME) is related to extracellular matrix (ECM) dynamics and has a broad fundamental and mechanistic role in tumorigenesis and cancer progression. We hypothesized that ECM regulators might play an essential role in pan-cancer attribution by causing a generic effect through its regulation of the dynamics of ECM alteration. By analyzing data from TCGA using GSEA and univariate Cox regression analysis, we found that ECM regulator genes were significantly enriched and contributed to mortality in various cancer types. Notably, UMAP analysis revealed that ECM regulator genes dominated the differences between tumor and adjacent normal tissues based on 59 or 31 pan-survival-related ECM gene sets. Subsequently, a five-gene signature consisting of the predominant ECM regulators ADAM12, MMP1, SERPINE1, PLOD3, and P4HA3 was identified. We found that this five-gene signature was pro-mortality in 18 types of cancer in TCGA, and validated eleven other cancer types in TCGA and seven types in the TARGET and CoMMpass databases using overall survival analysis. KEGG pathway enrichment and Pearson correlation analysis indicated that these five component genes that were correlated with specific ECM proteins involved in tumorigenesis from the ECM receptor interaction gene set. Additionally, the fitted results of a linear model were applied to strengthen the discovery, demonstrating that the five genes were correlated with immune infiltration score and especially associated with typically immunologically "cold" tumors. We thus conclude that the ADAM12, MMP1, SERPINE1, PLOD3, and P4HA3 signature showed a close association with a pan-cancer effect on prognosis and is related to ECM proteins in the TME which corresponding with immunologically "cold" cancer types.
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http://dx.doi.org/10.1002/cam4.3986DOI Listing
June 2021

High-efficiency removal of tetracycline by carbon-bridge-doped g-CN/FeO magnetic heterogeneous catalyst through photo-Fenton process.

J Hazard Mater 2021 Jun 7;418:126333. Epub 2021 Jun 7.

Jiangsu Baichuan High-Tech New Materials Co., Ltd, Nanjing, China.

Carbon-bridge-modified malonamide (MLD)/g-CN (CN) was prepared by copolymerization of MLD with urea and melamine and loaded with FeO for the high-efficiency removal of tetracycline (TC) in water under photo-Fenton. The prepared catalysts were characterized by SEM, TEM, N adsorption-desorption analysis, XPS, XRD, and FTIR, which proved that the modification method successfully introduced the C bridge into the carbon nitride molecular system and increased the structural defects of the catalyst. The Carbon-bridge-modified MLD/CN/FeO also had good visible-light response and charge-separation and transport abilities in the photoelectrochemical test. Degradation results showed that the photo-Fenton degradation of TC reached 95.8%, and the mineralization rate was 55.7% within 80 min at 80 mM HO dosage, 0.5 g/L catalyst dosage, and near-neutral pH by 0.8MLD/CN/FeO. Moreover, the oxidation products and mineralization pathways of TC were explored by LC-MS. Toxicity analysis indicated low environmental threat of the intermediates in TC mineralization. EPR analysis and HO decomposition efficiency analyses showed an improvement in the HO decomposition performance of 0.8MLD/CN/FeO. This work could provide a valuable insight for the application of heterogeneous photo-Fenton technology in wastewater treatment.
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http://dx.doi.org/10.1016/j.jhazmat.2021.126333DOI Listing
June 2021

A High-Resolution Ternary Model Demonstrates How PEGylated 2D Nanomaterial Stimulates Integrin α β on Cell Membrane.

Adv Sci (Weinh) 2021 06 23;8(11):e2004506. Epub 2021 Mar 23.

State Key Laboratory of Biochemical Engineering, Institute of Process Engineering, Chinese Academy of Sciences, No. 1 Bei-Er-Tiao, Zhong-Guan-Cun, Haidian District, Beijing, 100190, P. R. China.

Bio-nano interfaces are integral to all applications of nanomaterials in biomedicine. In addition to peptide-ligand-functionalized nanomaterials, passivation on 2D nanomaterials has emerged as a new regulatory factor for integrin activation. However, the mechanisms underlying such ligand-independent processes are poorly understood. Here, using graphene oxide passivated with polyethylene glycol (GO-PEG) as a test bed, a ternary simulation model is constructed that also includes a membrane and both subunits of integrin α β to characterize GO-PEG-mediated integrin activation on the cell membrane in a ligand-independent manner. Combined with the experimental findings, production simulations of the ternary model show a three-phase mechanotransduction process in the vertical interaction mode. Specifically, GO-PEG first induces lipid aggregation-mediated integrin proximity, followed by transmembrane domain rotation and separation, leading to the extension and activation of extracellular domains. Thus, this study presents a complete picture of the interaction between passivated 2D nanomaterials and cell membranes to mediate integrin activation, and provides insights into the potential de novo design and rational use of novel desirable nanomaterials at diverse bio-nano interfaces.
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http://dx.doi.org/10.1002/advs.202004506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188183PMC
June 2021

An Update on the Routes for the Delivery of Donepezil.

Mol Pharm 2021 Jun 8. Epub 2021 Jun 8.

Beijing Laboratory of Biomedical Materials, College of Materials Science and Engineering, Beijing University of Chemical Technology, Beijing 100029, P.R. China.

Dementia is a significant public health problem in the 21st century. Alzheimer's disease (AD) is an essential factor in dementia. Currently, the drugs used for the treatment of AD are mainly acetylcholine inhibitors (AChEIs). As an AChEI, donepezil (DP) can improve patients' cognitive ability with low side effects and has been accepted by most patients and doctors. For AD patients, the dosage regimen is also crucial due to aging and diseases. Although there are DP oral tablets on the market, there are still many problems to be solved. At present, more and more research is conducted to optimize the route of administration of DP to improve the self-administration of patients. The research fields of DP administration include oral administration, injection administration, intranasal administration, and transdermal administration. This Review is to present the development of different DP administrations and evaluates the advantages and limitations of those works, hoping to optimize the DP dosage regimen for AD patients.
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http://dx.doi.org/10.1021/acs.molpharmaceut.1c00290DOI Listing
June 2021

Adsorption-Reaction Processes Between Gelatin and PDMS-E Emulsion Droplets.

ACS Omega 2021 Jun 20;6(21):13915-13925. Epub 2021 May 20.

Shandong Provincial Key Laboratory of Molecular Engineering, School of Mathematics and Statistics, Qilu University of Technology Library, Qilu University of Technology (Shandong Academy of Sciences), Jinan 250353, P. R. China.

In this work, the effects of droplet size and reaction time on the adsorption-reaction processes between gelatin and α-[3-(2,3-epoxypropoxy) propyl]-ω-butyl-polydimethylsiloxane (PDMS-E) emulsion droplets were studied. Gelatin molecules were only physically adsorbed on the surface of the PDMS-E droplet in the 0-75 min range, which was unrelated to the droplet size (100-1000 nm). For the small-size droplets (<410 nm), the physical adsorption proceeded over 75 min followed by agglomeration. For middle-size droplets (410-680 nm), the physical adsorption finished at 125 min; subsequently, the nucleophilic reaction between the primary amino group and the epoxy group began to happen, and globular-like or core-shell colloidal particles were formed. For large-size droplets (>680 nm), the nucleophilic reaction occurred at 75 min and produced core-shell or multi-layered colloidal particles. In a word, the physical absorption or nucleophilic reaction between gelatin and PDMS-E emulsion droplets could be controlled by controlling the droplet size and reaction time. Furthermore, the soft tissue paper coated with large-size droplets exhibited excellent resistance to water permeability and flame-resistant performance, which were carried out by water resistance and flammability tests.
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http://dx.doi.org/10.1021/acsomega.1c01789DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8173617PMC
June 2021

Flow-induced segregation and dynamics of red blood cells in sickle cell disease.

Phys Rev Fluids 2020 May 4;5(5). Epub 2020 May 4.

Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706-1691.

Blood flow in sickle cell disease (SCD) can substantially differ from normal blood flow due to significant alterations in the physical properties of the red blood cells (RBCs). Chronic complications, such as inflammation of the endothelial cells lining blood vessel walls, are associated with SCD, for reasons that are unclear. Here, detailed boundary integral simulations are performed to investigate an idealized model flow flow in SCD, a binary suspension of flexible biconcave discoidal fluid-filled capsules and stiff curved prolate capsules that represent healthy and sickle RBCs, respectively, subjected to pressure-driven flow in a planar slit. The stiff component is dilute. The key observation is that, unlike healthy RBCs that concentrate around the center of the channel and form an RBC-depleted layer (i.e. cell-free layer) next to the walls, sickle cells are largely drained from the bulk of the suspension and aggregate inside the cell-free layer, displaying strong margination. These cells are found to undergo a rigid-body-like rolling orbit near the walls. A binary suspension of flexible biconcave discoidal capsules and stiff straight (non-curved) prolate capsules is also considered for comparison, and the curvature of the stiff component is found to play a minor role in the behavior. Additionally, by considering a mixture of flexible and stiff biconcave discoids, we reveal that rigidity difference by itself is sufficient to induce the segregation behavior in a binary suspension. Furthermore, the additional shear stress on the walls induced by the presence of cells is computed for the various cases. Compared to the small fluctuations in wall shear stress for a suspension of healthy RBCs, large local peaks in wall shear stress are observed for the binary suspensions, due to the proximity of the marginated stiff cells to the walls. This effect is most marked for the straight prolate capsules. As endothelial cells are known to mechanotransduce physical forces such as aberrations in shear stress and convert them to physiological processes such as activation of inflammatory signals, these results may aid in understanding mechanisms for endothelial dysfunction associated with SCD.
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http://dx.doi.org/10.1103/physrevfluids.5.053101DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174308PMC
May 2020

Multiplicity of stable orbits for deformable prolate capsules in shear flow.

Phys Rev Fluids 2020 Feb 28;5(2). Epub 2020 Feb 28.

Department of Chemical and Biological Engineering University of Wisconsin-Madison, Madison, WI 53706-1691.

This work investigates the orbital dynamics of a fluid-filled deformable prolate capsule in unbounded simple shear flow at zero Reynolds number using direct simulations. The motion of the capsule is simulated using a model that incorporates shear elasticity, area dilatation, and bending resistance. Here the deformability of the capsule is characterized by the nondimensional capillary number Ca, which represents the ratio of viscous stresses to elastic restoring stresses on the capsule. For a capsule with small bending stiffness, at a given Ca, the orientation converges over time towards a unique stable orbit independent of the initial orientation. With increasing Ca, four dynamical modes are found for the stable orbit, namely, rolling, wobbling, oscillating-swinging, and swinging. On the other hand, for a capsule with large bending stiffness, multiplicity in the orbit dynamics is observed. When the viscosity ratio ≲ 1, the long-axis of the capsule always tends towards a stable orbit in the flow-gradient plane, either tumbling or swinging, depending on Ca. When ≳ 1, the stable orbit of the capsule is a tumbling motion at low Ca, irrespective of the initial orientation. Upon increasing Ca, there is a symmetry-breaking bifurcation away from the tumbling orbit, and the capsule is observed to adopt multiple stable orbital modes including nonsymmetric precessing and rolling, depending on the initial orientation. As Ca further increases, the nonsymmetric stable orbit loses existence at a saddle-node bifurcation, and rolling becomes the only attractor at high Ca, whereas the rolling state coexists with the nonsymmetric state at intermediate values of Ca. A symmetry-breaking bifurcation away from the rolling orbit is also found upon decreasing Ca. The regime with multiple attractors becomes broader as the aspect ratio of the capsule increases, while narrowing as viscosity ratio increases. We also report the particle contribution to the stress, which also displays multiplicity.
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http://dx.doi.org/10.1103/physrevfluids.5.023603DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174403PMC
February 2020

Altered Resting-State Brain Activity in Schizophrenia and Obsessive-Compulsive Disorder Compared With Non-psychiatric Controls: Commonalities and Distinctions Across Disorders.

Front Psychiatry 2021 21;12:681701. Epub 2021 May 21.

Institute of Mental Health, Peking University Sixth Hospital, Beijing, China.

Schizophrenia (SCZ) and obsessive-compulsive disorder (OCD) are classified as two chronic psychiatric disorders with high comorbidity rate and shared clinical symptoms. Abnormal spontaneous brain activity within the cortical-striatal neural circuits has been observed in both disorders. However, it is unclear if the common or distinct neural abnormalities underlie the neurobiological substrates in the resting state. Resting-state fMRI data were collected from 88 patients with SCZ, 58 patients with OCD, and 72 healthy control subjects. First, we examined differences in amplitude of low-frequency fluctuations (ALFF) among three groups. Resting-state functional connectivity (rsFC) analysis with the brain region that showed different ALFF as the seed was then conducted to identify the changes in brain networks. Finally, we examined the correlation between the altered activities and clinical symptoms. Both the patients with SCZ and OCD showed increased ALFF in the right hippocampus and decreased ALFF in the left posterior cingulate cortex (PCC). SCZ patients exhibited increased ALFF in the left caudate [voxel-level family-wise error (FWE) < 0.05] and decreased rsFC between the left caudate and right cerebellum, which correlated with positive symptoms. The left caudate showed increased rsFC with the right thalamus and bilateral supplementary motor complex (SMC) in OCD patients (cluster-level FWE < 0.05). The hippocampus and PCC are common regions presenting abnormal local spontaneous neuronal activities in both SCZ and OCD, while the abnormality of the striatum can reflect the differences. Increased ALFF in the striatum and symptom-related weakened rsFC between the caudate and cerebellum showed SCZ specificity. Enhanced rsFC between the caudate and SMC may be a key characteristic in OCD. Our research shows the similarities and differences between the two diseases from the perspective of resting-state fMRI, which provides clues to understand the disease and find methods for treatment.
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http://dx.doi.org/10.3389/fpsyt.2021.681701DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8176119PMC
May 2021

Preschoolers' Approaches to Learning and Family-school Connections During COVID-19: An Empirical Study Based on a Wuhan Sample.

Early Child Educ J 2021 May 30:1-11. Epub 2021 May 30.

Wuhan University, Wuhan, Hubei China.

The concept, approaches to learning (ATL), is an important dimension of children's school readiness, which reflects children's enthusiasm and engagement in learning settings. Due to coronavirus disease 2019 (COVID-19), when preschools were shut down for months and children's social interactions were greatly limited, preschoolers' ATL might be negatively affected. However, strengthened family-school connections might have the potential to reduce the adverse effects of the pandemic. Based on a sample of 340 preschoolers from 30 classes of 6 preschools in Wuhan, China, we explored the association between family-preschool connections and preschoolers' ATL scores. The findings showed that the preschoolers' ATL were statistically and positively associated with parental attendance at the online parent-teacher meetings initiated by the preschools (standardized coefficient = 0.15). Policy implications regarding the enhancement of family-preschool connections are discussed.

Supplementary Information: The online version contains supplementary material available at 10.1007/s10643-021-01217-x.
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http://dx.doi.org/10.1007/s10643-021-01217-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164827PMC
May 2021

Docking-based generation of antibodies mimicking Cry1A/1B protein binding sites as potential insecticidal agents against diamondback moth (Plutella xylostella).

Pest Manag Sci 2021 Jun 6. Epub 2021 Jun 6.

Key Lab of Food Quality and Safety of Jiangsu Province-State Key Laboratory Breeding Base, Key Laboratory of Control Technology and Standard for Agro-product Safety and Quality, Ministry of Agriculture, Institute of Food Safety and Nutrition, Jiangsu Academy of Agricultural Sciences, 210014, Nanjing, China.

Background: Broad use of insecticidal Cry proteins from Bacillus thuringiensis in biopesticides and transgenic crops has resulted in cases of practical field resistance, highlighting the need for novel approaches to insect control. Previously we described an anti-Cry1Ab idiotypic-antibody (B12-scFv) displaying toxicity against rice leafroller (Cnaphalocrocis medinalis) larvae, supporting the potential of antibodies for pest control. The goal of the present study was to generate insecticidal antibodies against diamondback moth (Plutella xylostella) larvae.

Results: Four genetically engineered antibodies (GEAbs) were designed in silico from B12-scFv using 3D structure and docking predictions to alkaline phosphatase (ALP) as a Cry1Ac receptor in P. xylostella. Among these GEAbs, the GEAb-dV antibody consisting of two light chains had overlapping binding sites with Cry1A and Cry1B proteins and displayed high binding affinity to P. xylostella midgut brush border membrane (BBM) proteins. Proteins in BBM identified by pull-down assays as binding to GEAb-dV included an ABC transporter and V-ATPase subunit A protein. Despite lacking the α-helical structures in Cry1A that are responsible for pore formation, ingestion of GEAb-dV disrupted the P. xylostella larval midgut epithelium and resulted in toxicity. Apoptotic genes were activated in gut cells upon treatment with GEAb-dV .

Conclusion: This study describes the first insecticidal GEAb targeting P. xylostella by mimicking Cry proteins. Data support that GEAb-dV toxicity is associated to activation of intracellular cell death pathways, in contrast to pore-formation associated toxicity of Cry proteins. This work provides a foundation for the design of novel insecticidal antibodies for insect control.
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http://dx.doi.org/10.1002/ps.6499DOI Listing
June 2021

MLH1 Exon 12 Gene Deletion Leading to Lynch Syndrome: A Case Report.

Oncol Res Treat 2021 Jun 4:1-7. Epub 2021 Jun 4.

Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

Introduction: Deleterious heterozygous mutation of the MLH1 gene is an important cause of Lynch syndrome (LS), an autosomal dominant cancer caused by functional defects in the DNA mismatch repair (MMR) complex.

Case Report: The proband was a 35-year-old patient with confirmed colorectal cancer (CRC). Immunohistochemical (IHC) staining revealed the absence of MLH1 and PMS2 expression in the colorectal tissue specimens of the patient. Genetic counselling and tumor gene testing were performed using next-generation sequencing technology. The genetic tumor verification report showed the deletion of 4 bases in exon 12 of the tested MLH1 gene and a transcoding mutation. To our knowledge, this germline splice site mutation of MLH1 has not been reported before. The proband accepted several therapeutic regimens including PD-1 inhibitor and ultimately died of multiple organ failure.

Conclusion: Nonsense mutations and frameshift mutations of MMR genes are the most common causes of LS. Common mutations include those in MSH2, MLH1, MSH6, and PMS2. We report a mutation of MLH1 that has never been reported before. We recommend that patients with a history of colon or rectal cancer receive universal MMR or MSI testing and checkpoint inhibitor therapy for the first-line treatment of deficient MMR CRC.
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http://dx.doi.org/10.1159/000516659DOI Listing
June 2021

Apoptotic vesicles restore liver macrophage homeostasis to counteract type 2 diabetes.

J Extracell Vesicles 2021 May 24;10(7):e12109. Epub 2021 May 24.

State Key Laboratory of Military Stomatology & National Clinical Research Center for Oral Diseases & Shaanxi International Joint Research Center for Oral Diseases Center for Tissue Engineering School of Stomatology The Fourth Military Medical University Xi'an Shaanxi China.

Apoptosis is a naturally occurring process generating plenty of apoptotic vesicles (apoVs), but the feature, fate and function of apoVs remain largely unknown. Notably, as an appealing source for cell therapy, mesenchymal stem cells (MSCs) undergo necessary apoptosis and release apoVs during therapeutic application. In this study, we characterized and used MSC-derived apoVs to treat type 2 diabetes (T2D) mice, and we found that apoVs were efferocytosed by macrophages and functionally modulated liver macrophage homeostasis to counteract T2D. We showed that apoVs can induce macrophage reprogramming at the transcription level in an efferocytosis-dependent manner, leading to inhibition of macrophage accumulation and transformation of macrophages towards an anti-inflammation phenotype in T2D liver. At the molecular level, we discovered that calreticulin (CRT) was exposed on the surface of apoVs to act as a critical 'eat-me' signal mediating apoV efferocytosis and macrophage regulatory effects. Importantly, we demonstrated that CRT-mediated efferocytosis of MSC-derived apoVs contributes to T2D therapy with alleviation of T2D phenotypes including glucose intolerance and insulin resistance. These findings uncover that functional efferocytosis of apoVs restores liver macrophage homeostasis and ameliorates T2D.
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http://dx.doi.org/10.1002/jev2.12109DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8144839PMC
May 2021