Publications by authors named "Huan Cao"

82 Publications

PIN1 Protects Hair Cells and Auditory HEI-OC1 Cells against Senescence by Inhibiting the PI3K/Akt/mTOR Pathway.

Oxid Med Cell Longev 2021 2;2021:9980444. Epub 2021 Jun 2.

Department of Otorhinolaryngology, The Second Hospital of Hebei Medical University, No. 215 West Heping Road, Shijiazhuang 050000, China.

A growing amount of evidence has confirmed the crucial role of the prolyl isomerase PIN1 in aging and age-related diseases. However, the mechanism of PIN1 in age-related hearing loss (ARHL) remains unclear. Pathologically, ARHL is primarily due to the loss and dysfunction of hair cells (HCs) and spiral ganglion cells (SGCs) in the cochlea. Therefore, in this study, we aimed to investigate the role of PIN1 in protecting hair cells and auditory HEI-OC1 cells from senescence. Enzyme-linked immunosorbent assays, immunohistochemistry, and immunofluorescence were used to detect the PIN1 protein level in the serum of ARHL patients and C57BL/6 mice in different groups, and in the SGCs and HCs of young and aged C57BL/6 mice. In addition, a model of HEI-OC1 cell senescence induced by HO was used. Adult C57BL/6 mice were treated with juglone, or juglone and NAC, for 4 weeks. Interestingly, we found that the PIN1 protein expression decreased in the serum of patients with ARHL, in senescent HEI-OC1 cells, and in the cochlea of aged mice. Moreover, under HO and juglone treatment, a large amount of ROS was produced, and phosphorylation of p53 was induced. Importantly, PIN1 expression was significantly increased by treatment with the p53 inhibitor pifithrin-. Overexpression of PIN1 reversed the increased level of p-p53 and rescued HEI-OC1 cells from senescence. Furthermore, PIN1 mediated cellular senescence by the PI3K/Akt/mTOR signaling pathway. In vivo data from C57BL/6 mice showed that treatment with juglone led to hearing loss. Taken together, these findings demonstrated that PIN1 may act as a vital modulator in hair cell and HEI-OC1 cell senescence.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/9980444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273041PMC
June 2021

Heme Oxygenase-1-Modified Bone Marrow Mesenchymal Stem Cells Combined with Normothermic Machine Perfusion Repairs Bile Duct Injury in a Rat Model of DCD Liver Transplantation via Activation of Peribiliary Glands through the Wnt Pathway.

Stem Cells Int 2021 1;2021:9935370. Epub 2021 Jul 1.

Department of Organ Transplantation, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin 300192, China.

Livers from donors after circulatory death (DCD) are inevitably exposed to a longer warm ischemic period, which might increase the incidence of postoperative bile duct complications. Bone marrow mesenchymal stem cells (BMMSCs) have tissue repair properties. The present study was aimed at exploring the repair effect of heme oxygenase-1- (HO-1-) modified BMMSCs (HO-1/BMMSCs) combined with normothermic machine perfusion (NMP) on bile duct injury after DCD liver transplantation and at revealing the underlying mechanisms. Rat livers were exposed to warm ischemia for 30 min; then, NMP was performed through the portal vein for 4 h with BMMSCs, HO-1/BMMSCs, or neither before implantation. Obvious bile duct histological damage and liver functional damage were observed postoperatively. In the group treated with HO-1/BMMSCs combined with NMP (HBP group), liver functions and bile duct histology were improved; meanwhile, cell apoptosis was reduced and cell proliferation was active. A large number of regenerative cells appeared at the injured site, and the defective bile duct epithelium was restored. Dilatation of peribiliary glands (PBGs), proliferation of PBG cells, high expression of vascular endothelial growth factor (VEGF), and increased proportion of bile duct progenitor cells with stem/progenitor cells biomarkers were observed. Blocking Wnt signaling significantly inhibited the repair effect of HO-1/BMMSCs on bile duct injury. In conclusion, HO-1/BMMSCs combined with NMP were relevant to the activation of biliary progenitor cells in PBGs which repaired bile duct injury in DCD liver transplantation via the Wnt signaling pathway. Proliferation and differentiation of PBG cells were involved in the renewal of the injured biliary epithelium.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2021/9935370DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8275434PMC
July 2021

Protective Effects of Bone Marrow Mesenchymal Stem Cells (BMMSCS) Combined with Normothermic Machine Perfusion on Liver Grafts Donated After Circulatory Death via Reducing the Ferroptosis of Hepatocytes.

Med Sci Monit 2021 Jun 11;27:e930258. Epub 2021 Jun 11.

Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin, China (mainland).

BACKGROUND To improve the quality of liver grafts from extended-criteria donors donated after circulatory death (DCD), this study explored whether bone marrow mesenchymal stem cells (BMMSCs) combined with normothermic machine perfusion (NMP) have protective effects on DCD donor livers and the effects of ferroptosis in this procedure. MATERIAL AND METHODS Twenty-four male rat DCD donor livers were randomly and averagely divided into normal, static cold storage (SCS), NMP, and NMP combined with BMMSCs groups. Liver function, bile secretion, and pathological features of DCD donor livers were detected to evaluate the protective effects of NMP and BMMSCs on DCD donor livers. Hydrogen peroxide was used to induce an oxidative stress model of hepatocyte IAR-20 cells to evaluate the protective effects of BMMSCs in vitro. RESULTS Livers treated with NMP combined with BMMSCs showed better liver function, relieved histopathological damage, reduced oxidative stress injury and ferroptosis, and the mechanism of reduction was associated with downregulation of intracellular reactive oxygen species (ROS) and free Fe²⁺ levels. BMMSCs showed significant protective effects on the ultrastructure of DCD donor livers and ROS-induced injury to IAR-20 cells under electron microscopy. BMMSCs also significantly improved the expression level of microtubule-associated protein 1 light chain 3 (LC3)-II in both DCD donor livers and ROS-induced injured IAR-20 cells, including upregulating the expression of ferritin. CONCLUSIONS BMMSCs combined with NMP could reduce the level of ROS and free Fe²⁺ in oxidative stress damaged rat DCD donor livers, potentially reduce the ferroptosis in hepatocytes, and repair both morphology and function of DCD donor livers.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.12659/MSM.930258DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8204680PMC
June 2021

A novel human arterial wall-on-a-chip to study endothelial inflammation and vascular smooth muscle cell migration in early atherosclerosis.

Lab Chip 2021 06;21(12):2359-2371

School of Mechanical and Aerospace Engineering, Nanyang Technological University, Singapore, 639798, Singapore. and Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 308232, Singapore.

Mechanistic understanding of atherosclerosis is largely hampered by the lack of a suitable in vitro human arterial model that recapitulates the arterial wall structure, and the interplay between different cell types and the surrounding extracellular matrix (ECM). This work introduces a novel microfluidic endothelial cell (EC)-smooth muscle cell (SMC) 3D co-culture platform that replicates the structural and biological aspects of the human arterial wall for modeling early atherosclerosis. Using a modified surface tension-based ECM patterning method, we established a well-defined intima-media-like structure, and identified an ECM composition (collagen I and Matrigel mixture) that retains the SMCs in a quiescent and aligned state, characteristic of a healthy artery. Endothelial stimulation with cytokines (IL-1β and TNFα) and oxidized low-density lipoprotein (oxLDL) was performed on-chip to study various early atherogenic events including endothelial inflammation (ICAM-1 expression), EC/SMC oxLDL uptake, SMC migration, and monocyte-EC adhesion. As a proof-of-concept for drug screening applications, we demonstrated the atheroprotective effects of vitamin D (1,25(OH)2D3) and metformin in mitigating cytokine-induced monocyte-EC adhesion and SMC migration. Overall, the developed arterial wall model facilitates quantitative and multi-factorial studies of EC and SMC phenotype in an atherogenic environment, and can be readily used as a platform technology to reconstitute multi-layered ECM tissue biointerfaces.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1039/d1lc00131kDOI Listing
June 2021

Sialic acid-binding immunoglobulin-like lectin (Sigelac)-15 is a rapidly internalised cell-surface antigen expressed by acute myeloid leukaemia cells.

Br J Haematol 2021 Jun 5;193(5):946-950. Epub 2021 May 5.

Department of Microbiology and Immunology (DMI), The University of Melbourne, Melbourne, Australia.

Sialic acid-binding immunoglobulin-like lectin (Siglec)-15 has recently been identified as a critical tumour checkpoint, augmenting the expression and function of programmed death-ligand 1. We raised a monoclonal antibody, A9E8, specific for Siglec-15 using phage display. A9E8 stained myeloid leukaemia cell lines and peripheral cluster of differentiation (CD)33 blasts and CD34 leukaemia stem cells from patients with acute myeloid leukaemia (AML). By contrast, there was minimal expression on healthy donor leucocytes or CD34 stem cells from non-AML donors, suggesting targeting Siglec-15 may have significant therapeutic advantages over its fellow Siglec CD33. After binding, A9E8 was rapidly internalised (half-life of 180 s) into K562 cells. Antibodies to Siglec-15 therefore hold therapeutic potential for AML treatment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/bjh.17496DOI Listing
June 2021

Combined passivators regulate the heavy metal accumulation and antioxidant response of Brassica chinensis grown in multi-metal contaminated soils.

Environ Sci Pollut Res Int 2021 May 1. Epub 2021 May 1.

College of Resources and Environment, Huazhong Agricultural University, Wuhan, 430070, China.

Passivation of heavy metals is one of the most efficient techniques to remediate soil pollution. However, passivators with single component are usually unsatisfactory in the case of multi-metal contaminated soils. To resolve this problem, a series of combined passivators containing different ratios of Fe-Mn ore, Fe powder, zeolite, bentonite, etc. were designed and used to study their effects on the growth, heavy metal accumulation, and the antioxidant response of Chinese cabbage (Brassica chinensis L.) as well as the soil available forms of heavy metals in a copper refinery's multi-metal (As, Cd, Pb, Cu) contaminated yellow-brown soil and an artificially contaminated (As, Cd, Pb, Cu) calcareous alluvial soil. The results showed that compared with the control, the addition of combined passivators significantly promoted cabbage growth, with the biomass increase up to 1.77 and 3.54 times in yellow-brown soil and calcareous alluvial soil, respectively. The activity of antioxidant enzymes (SOD, CAT, POD) and the content of malondialdehyde (MDA) and glutathione (GSH) decreased, while the chlorophyll content increased significantly, as compared with no passivators. In addition, passivator application decreased As, Cd, Pb, and Cu contents in shoots and roots by 34.8%, 45.6%, 34.9%, and 11.1% and 49.2%, 63.8%, 38.6%, and 46.4% in yellow-brown soil and by 29.8%, 27.3%, 26.8%, and 25.5% and 45.8%, 55.2%, 61.8%, and 5.7% in calcareous alluvial soil, respectively. Besides, the content of soil available heavy metals was reduced by 8.0-17.1% in yellow-brown soil and 3.3-19.1% in calcareous alluvial soil after the application of passivators. The results indicated that the combined passivators formulated in this experiment could efficiently reduce the content of the multi-metals in cabbage and relieve the oxidant stress and could be used as a way to remediate multi-metal polluted soils.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11356-021-14193-xDOI Listing
May 2021

Hippocampal proteomic analysis reveals activation of necroptosis and ferroptosis in a mouse model of chronic unpredictable mild stress-induced depression.

Behav Brain Res 2021 Jun 26;407:113261. Epub 2021 Mar 26.

Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Road, Wuhan, 430030, Hubei, China. Electronic address:

Neuronal loss has been identified in depression, but its mechanisms are not fully understood. Proteomic analyses provide a novel insight to explore the potential mechanisms of such pathological alterations. In this study, mice were treated with chronic unpredictable mild stress (CUMS) for 2 months to establish depression models. The hippocampus was analyzed for proteomic patterns by mass spectrometry followed by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Behavioral tests showed that mice receiving CUMS showed depression-like symptoms such as anhedonia in the sucrose preference test (SPT) and behavioral despair in the forced swimming test (FST). CUMS induced anxiety-like behaviors in the open field test (OFT), but did not impair spatial learning and memory ability in the Morris water maze (MWM) test. Out of 4046 quantified proteins, 47 differentially expressed proteins were obtained between the CUMS and control groups. These proteins were functionally enriched in a series of biological processes. Among the notably enriched pathways, necroptosis and ferroptosis were significantly activated. Western blot and biochemical assay analyses identified changes in receptor-interacting protein kinase 3 (RIP3), phosphorylated mixed lineage kinase domain-like protein (p-MLKL), ferritin light chain 1 (Ftl1) and lipid peroxidation that were related to necroptosis and ferroptosis. Further, we found reduced levels of alpha-crystallin B (Cryab) and brain-derived neurotrophic factor (BDNF), which were also associated with neuronal survival. Our study highlighted that necroptosis and ferroptosis were involved in depression and partially account for neuronal loss, thereby providing potentially novel targets for the treatment of depression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbr.2021.113261DOI Listing
June 2021

A 3D physio-mimetic interpenetrating network-based platform to decode the pro and anti-tumorigenic properties of cancer-associated fibroblasts.

Acta Biomater 2021 Mar 22. Epub 2021 Mar 22.

School of Materials Science and Engineering, Nanyang Technological University, 50 Nanyang Avenue, Singapore 639798, Singapore; School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore. Electronic address:

Three-dimensional (3D) biomaterials with physiologically relevant and experimentally tractable biomechanical features are important platforms to advance our understanding of the influence of tissue mechanics in disease progression. Herein, an interpenetrating network (IPN) of collagen and alginate 3D culture system with tunable extracellular microstructure and mechanics is exploited as a tumor stroma proxy to study phenotypic plasticity of colorectal cancer-associated fibroblasts (CAF). In combination with Next Generation Sequencing (NGS) data analysis, we demonstrated that tuning the storage modulus of the IPN hydrogel between 49 and 419 Pa can trigger a reversible switch between an inflammatory (i-state, α-SMAIL-6) and myofibroblastic (m-state, α-SMAIL-6) state in CAF that is dependent on the polymer network confinement effect and ROS-HIF1-α mechanotransduction signaling axis. Secretome from m-state CAF upregulated several epithelial-mesenchymal-transition (EMT) transcripts and induced robust scattering in DLD-1, HCT116, and SW480 human colorectal adenocarcinoma, while the EMT-inducing capacity is muted in i-state CAF, suggestive of an anti-tumorigenic role. Our findings were further validated through Gene Expression Profiling Interactive Analysis (GEPIA), which showed that cytokines secreted at higher levels by i-state CAF are correlated (p < 0.05) with good overall colorectal cancer patient survival. Therefore, 3D network density and spatial cellular confinement are critical biophysical determinants that can profoundly influence CAF states, paracrine signaling, and EMT-inducing potential. STATEMENT OF SIGNIFICANCE: The communication between cancer cells and cancer-associated fibroblasts (CAF) contributes to tumor metastasis. CAF represent a diverse population of cellular subsets that can either promote or restrain tumor progression. However, the origin and cause of CAF heterogeneity remain elusive, limiting CAF-directed therapies for clinical use. We studied the dynamic phenotypes of CAF using a 3D physio-mimetic culture platform consisting of an interpenetrating collagen-alginate network. Combined with transcriptomic stratification and correlative analysis using cancer patient dataset, we showed phenotypic interconversion between inflammatory and myofibroblastic states, with anti- and pro-tumorigenic functions, in human colorectal CAF. This multidisciplinary study reveals the functional diversity of colorectal CAF caused by biophysical cues. The finding will influence the development of new CAF biomarkers and cancer therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.actbio.2021.03.037DOI Listing
March 2021

Effectiveness of cognitive behavior therapy for sleep disturbance and glycemic control in persons with type 2 diabetes mellitus: A community-based randomized controlled trial in China.

World J Diabetes 2021 Mar;12(3):292-305

Department of Control and Prevention of Chronic Non-communicable Diseases, Xuzhou Center for Disease Control and Prevention, Xuzhou 221006, Jiangsu Province, China.

Background: Poor sleep quality is a common clinical feature in patients with type 2 diabetes mellitus (T2DM), and often negatively related with glycemic control. Cognitive behavioral therapy (CBT) may improve sleep quality and reduce blood sugar levels in patients with T2DM. However, it is not entirely clear whether CBT delivered by general practitioners is effective for poor sleep quality in T2DM patients in community settings.

Aim: To test the effect of CBT delivered by general practitioners in improving sleep quality and reducing glycemic levels in patients with T2DM in community.

Methods: A cluster randomized controlled trial was conducted from September 2018 to October 2019 in communities of China. Overall 1033 persons with T2DM and poor sleep quality received CBT plus usual care or usual care. Glycosylated hemoglobin A1c (HbAlc) and sleep quality [Pittsburgh Sleep Quality Index (PSQI)] were assessed. Repeated measures analysis of variance and generalized linear mixed effects models were used to estimate the intervention effects on hemoglobin A1c and sleep quality.

Results: The CBT group had 0.64, 0.50, and 0.9 lower PSQI scores than the control group at 2 mo, 6 mo, and 12 mo, respectively. The CBT group showed 0.17 and 0.43 lower HbAlc values than the control group at 6 mo and 12 mo. The intervention on mean ΔHbAlc values was significant at 12 mo ( = 3.68, < 0.01) and that mean ΔPSQI scores were closely related to ΔHbAlc values ( = 7.02, < 0.01). Intention-to-treat analysis for primary and secondary outcomes showed identical results with completed samples. No adverse events were reported.

Conclusion: CBT delivered by general practitioners, as an effective and practical method, could reduce glycemic levels and improve sleep quality for patients with T2DM in community.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.4239/wjd.v12.i3.292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7958479PMC
March 2021

Red blood cell mannoses as phagocytic ligands mediating both sickle cell anaemia and malaria resistance.

Nat Commun 2021 03 19;12(1):1792. Epub 2021 Mar 19.

School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, UK.

In both sickle cell disease and malaria, red blood cells (RBCs) are phagocytosed in the spleen, but receptor-ligand pairs mediating uptake have not been identified. Here, we report that patches of high mannose N-glycans (ManGlcNAc), expressed on diseased or oxidized RBC surfaces, bind the mannose receptor (CD206) on phagocytes to mediate clearance. We find that extravascular hemolysis in sickle cell disease correlates with high mannose glycan levels on RBCs. Furthermore, Plasmodium falciparum-infected RBCs expose surface mannose N-glycans, which occur at significantly higher levels on infected RBCs from sickle cell trait subjects compared to those lacking hemoglobin S. The glycans are associated with high molecular weight complexes and protease-resistant, lower molecular weight fragments containing spectrin. Recognition of surface N-linked high mannose glycans as a response to cellular stress is a molecular mechanism common to both the pathogenesis of sickle cell disease and resistance to severe malaria in sickle cell trait.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41467-021-21814-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979802PMC
March 2021

The red blood cell as a novel regulator of human B-cell activation.

Immunology 2021 Aug 6;163(4):436-447. Epub 2021 May 6.

Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK.

Non-immune cells are increasingly recognized as important in regulating immunity, but the role of red blood cells (RBC) remains relatively unexplored, despite their abundance in the circulation and a cell surface rich in potential ligands. Here, we determine whether RBC influence the activation state of human B cells. Separation of RBC from peripheral blood mononuclear cells increased B-cell expression of HLA-DR/DP/DQ, whilst reconstitution reduced the levels of B-cell activation markers HLA-DR/DP/DQ, CD86, CD69 and CD40, as well as decreasing proliferative responses and IgM secretion. Inhibition of B cells required contact with RBC and was abrogated by either removal of sialic acids from RBC or blocking the corresponding lectin receptor CD22 on B cells. Chronic lymphocytic leukaemia B cells express low levels of CD22 and were less susceptible to inhibition by RBC, which may contribute to their activated phenotype. Taken together, the results identify a novel mechanism that may suppress inappropriate responsiveness of healthy B cells whilst circulating in the bloodstream.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/imm.13327DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274151PMC
August 2021

Artemisinin protects endothelial function and vasodilation from oxidative damage via activation of PI3K/Akt/eNOS pathway.

Exp Gerontol 2021 05 6;147:111270. Epub 2021 Feb 6.

School of Medical Science, Jinan University, Guangzhou, China. Electronic address:

Introduction: Previous studies showed that artemisinin (ART) may be useful in the protection against the early development of atherosclerosis, but the effects of ART on vasodilation and eNOS remained unclear.

Objectives And Methods: In the current study, we investigated the protective effect of ART on endothelial cell injury induced by oxidative stress and its underlying mechanism via MTT assay, Flow Cytometry Assay, Vasodilation study, Western blotting and vivo assay.

Results: We found that pretreatment of human umbilical vein endothelial cells (HUVECs) with ART significantly suppressed H2O2-induced cell death by decreasing the extent of oxidation and MDA activity, activating SOD, increasing NO production and inhibiting caspase 3/7 activity. Meanwhile, we also found that ART was able to activate PI3K/Akt/eNOS pathway. PI3K inhibitor LY294002 or Akt kinase specific inhibitor Akt inhibitor VIII blocked the protective effect of ART. To explore the effect of ART in the damage of vasodilation induced by H2O2 in mice, we treated the aortic ring from C57BL/6 mice with H2O2 with or without ART, the results demonstrated that ART ameliorated endothelium-dependent vasodilation damage induced by H2O2.

Conclusion: Taken together, these data suggest that ART is able to protect endothelial function and vasodilation from oxidative damage, at least in part through activation of PI3K/Akt/eNOS pathway. Our findings indicate that artemisinin maybe as a potential therapeutic agent for patients with atherosclerosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.exger.2021.111270DOI Listing
May 2021

Functional abnormalities of striatum are related to the season-specific effect on schizophrenia.

Brain Imaging Behav 2021 Jan 4. Epub 2021 Jan 4.

The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, No. 4, Section 2, North Jianshe Road, Chengdu, 610054, People's Republic of China.

Schizophrenia is a syndrome that is typically accompanied by delusions, hallucinations and cognitive impairments. Specifically, abundant evidences support the notion that more people diagnosed with schizophrenia are born during fall-winter than spring-summer. Although pathophysiological of schizophrenia might be associated with abnormal brain functional network, little is currently known the relationship between season and deficient brain functional network of schizophrenia. To investigate this issue, in this study 51 schizophrenic subjects and 72 healthy controls underwent MRI scanning to detect the brain functional mapping, each at spring-summer and fall-winter season throughout the year. The data-driven method was used to measure the blood oxygen metabolism variability (BOMV). Decreased BOMV in spring-summer while increased in fall-winter were observed within dopaminergic network of schizophrenic subjects, including striatum, thalamus, and hippocampus. The post hoc analysis exploring the coupling among changed BOMV regions, confirmed that a positive relationship, between pallidum and hippocampus existed in fall-winter healthy controls, but not in fall-winter schizophrenic subjects. These findings identified that seasonal effect on striatum might be associated with modulation of striatum-hippocampus. Our results provide a new insight into the role of season in understanding the pathophysiological of schizophrenia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11682-020-00430-3DOI Listing
January 2021

[Diagnosis and treatment of 12 cases of sexual activity-related hematuria: Experience and literature review].

Zhonghua Nan Ke Xue 2020 Sep;26(9):815-819

Department of Urology, Changhai Hospital, Naval Medical University, Shanghai 200433, China.

Objective: To summarize and analyze the experience in the diagnosis and treatment of sexual activity-related hematuria.

Methods: A retrospective analysis was conducted on 12 cases of sexual activity-related hematuria treated in Changhai Hospital from October 2015 to April 2019. The patients ranged in age between 31 and 59 years, with a disease course of 2 weeks to 25 years, 6 complaining of urethral bleeding at penile erection and another 6 hematuria immediately after ejaculation, including 2 accompanied by hemospermia. All the patients underwent urethroscopy and cauterization of the lesioned urethral mucosa with the electric excision ring or holmium laser. In addition, one of the patients received seminal tract endoscopic exploration and seminal vesicle irrigation, and another one seminal tract endoscopy and transurethral resection of the prostate.

Results: All the patients were diagnosed with posterior urethral varicosity, one accompanied with bulbar and posterior urethral varicosity, one with seminal vesiculitis, and still another with BPH. The patients were followed up for 3-45 (mean 23.5) months, during which the symptoms of sexual activity-related hematuria disappeared in 11 cases, with smooth urination and no recurrence, and post-ejaculation hematuria developed in one case at 2 and 10 months postoperatively but never again thereafter. No complications, such as epididymitis, urethral stricture and ED, were observed in any of the patients.

Conclusions: Urethral varicosity should be first considered in patients with painless hematuria immediately after penile erection or sexual activity though other conditions such as seminal vesicle bleeding can also be taken into account. Urethroscopy combined with seminal tract endoscopy is effective in the diagnosis and treatment of sexual activity-related hematuria.
View Article and Find Full Text PDF

Download full-text PDF

Source
September 2020

A Cross-Sectional Study of Psychological Status in Different Epidemic Areas in China After the COVID-19 Outbreak.

Front Psychiatry 2020 5;11:575705. Epub 2020 Nov 5.

Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

The outbreak of coronavirus disease 2019 in Wuhan, Hubei Province, China has seriously affected people's mental health. We aimed to assess the psychological impact of the coronavirus disease 2019 on health care workers and non-health care workers in three different epidemic areas in China and to identify independent risk factors. We surveyed 1,020 non-health care workers and 480 health care workers in Wuhan, other cities in Hubei except Wuhan and other provinces in China except Hubei. Health care workers in Hubei had higher levels of anxiety and depression than non-health care workers ( < 0.05), but there was no such difference in other provinces in China except Hubei ( > 0.05). Compared with other regions, health care workers in Wuhan was more anxious ( < 0.05), and this anxiety may be caused by concerns about occupational exposure and wearing protective clothing for a long time daily; health care workers in Hubei had more obvious depression ( < 0.05), which may be associated with long days participating in epidemic work and wearing protective clothing for a long time daily. Meanwhile, 62.5% of health care workers were proud of their work. The anxiety and depression of non-health care workers in Wuhan were also the most serious. In Wuhan, where the epidemic is most severe, levels of anxiety and depression seem to be higher, especially among health care workers. This information may help to better prepare for future events.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fpsyt.2020.575705DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674662PMC
November 2020

Effect of a Boric Acid Corrosive Environment on the Microstructure and Properties of Concrete.

Materials (Basel) 2020 Nov 8;13(21). Epub 2020 Nov 8.

College of Materials Science and Engineering, Nanjing Tech University, Nanjing 211800, China.

Boric acid, a weak acid, is often used to shield neutrons in water cooling systems in nuclear power stations. The leakage of boric acid in water cooling systems damages the concrete structure and affects the safety of nuclear power engineering. In this experiment, concrete specimens were cured with boric acid at 20, 40, and 70 °C to study the effect of boric acid on the microstructure and properties of concrete. X-ray diffraction (XRD) and thermogravimetry and differential scanning calorimetry (TG-DSC) were used to analyze the change in mineral composition. The microstructure was examined by scanning electron microscope (SEM). The porosity of the concrete was examined by mercury intrusion porosimetry (MIP). The results show that the performance of specimens was stable under the curing conditions of 20 and 40 °C. Under the curing environment of 70 °C, the performance of concrete cured with 0, 2000, and 7000 ppm concentrations was stable, but the compressive strength of the 180,000 ppm specimen was reduced by 27.8% and suffered the most serious loss of mass and surface corrosion, with the most harmful pores. The high concentration of boric acid seriously damaged the surface structure of concrete, which is the main reason for its loss of properties. This situation is extremely dangerous in nuclear power engineering, so the effect of boric acid leakage cannot be ignored.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ma13215036DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7664702PMC
November 2020

The Purple Leaf () Mutation Regulates Leaf Color by Altering the Anthocyanin and Chlorophyll Contents in Rice.

Plants (Basel) 2020 Nov 3;9(11). Epub 2020 Nov 3.

The Key Laboratory for Crop Germplasm Resource of Zhejiang Province, and Department of Agronomy, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China.

The anthocyanin biosynthesis attracts strong interest due to the potential antioxidant value and as an important morphological marker. However, the underlying mechanism of anthocyanin accumulation in plant tissues is not clearly understood. Here, a rice mutant with a purple color in the leaf blade, named , was developed from wild type (WT), Zhenong 41, with gamma ray treatment. By map-based cloning, the gene was located on the short arm of chromosome 6. The multiple mutations, such as single nucleotide polymorphism (SNP) at -702, -598, -450, an insertion at -119 in the promoter, three SNPs and one 6-bp deletion in the 5'-UTR region, were identified, which could upregulate the expression of to accumulate anthocyanin. Subsequently, the transcript level of structural genes in the anthocyanin biosynthesis pathway, including and , was elevated significantly. Histological analysis revealed that the light attenuation feature of anthocyanin has degraded the grana and stroma thylakoids, which resulted in poor photosynthetic efficiency of purple leaves. Despite this, the photoabatement and antioxidative activity of anthocyanin have better equipped the mutant to minimize the oxidative damage. Moreover, the contents of abscisic acid (ABA) and cytokanin (CK) were elevated along with anthocyanin accumulation in the mutant. In conclusion, our results demonstrate that activation of could be responsible for the purple coloration in leaves by accumulating excessive anthocyanin and further reveal that anthocyanin acts as a strong antioxidant to scavenge reactive oxygen species (ROS) and thus play an important role in tissue maintenance.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/plants9111477DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7693866PMC
November 2020

Identification of MSC-AS1, a novel lncRNA for the diagnosis of laryngeal cancer.

Eur Arch Otorhinolaryngol 2021 Apr 20;278(4):1107-1118. Epub 2020 Oct 20.

Department of Otorhinolaryngology, The Second Hospital of Hebei Medical University, No. 215 West Heping Road, Shijiazhuang, 050000, People's Republic of China.

Purpose: Our study was aimed to identify potential lncRNAs related to laryngeal cancer (LC) and explore their potential regulatory mechanisms.

Methods: RNA sequencing data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases were used to identify differentially expressed genes (DEGs). Receiver operating characteristic (ROC) curve analysis was performed to analyze the sensitivity and specificity of differentially expressed lncRNAs (DElncRNAs) as biomarkers. Weighted gene co-expression network analysis (WGCNA) was applied to identify co-expressed DElncRNAs and differentially expressed mRNAs (DEmRNAs) associated with clinical indicators. We performed functional enrichment analysis on target genes and constructed a lncRNA-miRNA-mRNA ceRNA network. The expression of lncRNA and mRNAs in ceRNA network were validated via RT-qPCR.

Results: By differential expression analyzing TCGA and GEO data, 6 up-regulated DElncRNAs were consistently identified, and their predictive performance were suggested to be considerable via ROC curve. 1998 DEmRNAs and 6 lncRNAs were involved in the construction of WGCNA network, in which the MEblue module was positively correlated with clinical stage. Functional enrichment analysis of this module suggested that the functions of DEmRNAs were closely involved in PI3K/Akt pathway. A ceRNA network composed of MSC-AS1, miR-429, COL4A1 and ITGAV was constructed. It was verified by RT-qPCR that the lncRNA and mRNAs in the ceRNA network were highly expressed in multiple LC tissues.

Conclusions: This study identified lncRNA MSC-AS1 as a potential biomarker of LC. Besides, we constructed a ceRNA network, which provides a basis for the research of ceRNA in LC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00405-020-06427-4DOI Listing
April 2021

, a Potential Genetic Editing Target for Drought and Salinity Stress Tolerance in .

Plants (Basel) 2020 Oct 10;9(10). Epub 2020 Oct 10.

Institute of Crop Science, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou 310058, China.

belongs to the miR156/miR529/miR535 superfamily, a highly conserved miRNA family in plants. is involved in regulating the cold-stress response, modulating plant development, and determining panicle architecture and grain length. However, the role that plays in plant responses to drought and salinity are elusive. In the current study, molecular and genetic engineering techniques were used to elucidate the possible role of in response to NaCl, PEG(Poly ethylene glycol), ABA(Abscisic acid), and dehydration stresses. Our results showed that is induced under stressed conditions as compared to control. With transgenic and CRISPR/Cas9 knockout system techniques, our results verified that either inhibition or knockout of in rice could enhance the tolerance of plants to NaCl, ABA, dehydration and PEG stresses. In addition, the overexpression of significantly reduced the survival rate of rice seedlings during PEG and dehydration post-stress recovery. Our results demonstrated that negatively regulates the stress response in rice. Moreover, our practical application of CRISPR/Cas9 mediated genome editing created a homozygous 5 bp deletion in the coding sequence of , demonstrating that could be a useful genetic editing target for drought and salinity tolerance and a new marker for molecular breeding of .
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/plants9101337DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7601473PMC
October 2020

lncRNA RASSF8‑AS1 suppresses the progression of laryngeal squamous cell carcinoma via targeting the miR‑664b‑3p/TLE1 axis.

Oncol Rep 2020 Nov 16;44(5):2031-2044. Epub 2020 Sep 16.

Department of Otorhinolaryngology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei 050000, P.R. China.

Long non‑coding (lnc)RNAs have been found to play a crucial role in tumor progression. The present study aimed to investigate the association between lncRNA RASSF8‑AS1 and laryngeal squamous cell carcinoma (LSCC) and the underlying mechanisms. Reverse transcription‑quantitative PCR was used to measure the mRNA expression level of RASSF8‑AS1, microRNA(miR)‑664b‑3p and transducin‑like enhancer of split 1 (TLE1) in LSCC. The associations between RASSF8‑AS1 and miR‑664b‑3p, and between miR‑664b‑3p and TLE1 were investigated using a dual luciferase reporter assay, while the former was further verified using an RNA immunoprecipitation (RIP) assay. The association between RASSF8‑AS1 and miR‑664b‑3p on cell biological functions was investigated in vitro using MTS, colony formation and Transwell assays. The RASSF8‑AS1 mRNA expression level was decreased in LSCC cell lines and carcinoma tissues, while overexpression of RASSF8‑AS1 reduced the migration, invasion and proliferation abilities of LSCC cells. Furthermore, luciferase and RIP assays confirmed that RASSF8‑AS1 was a competitive endogenous (ce)RNA by sponging miR‑664b‑3p to activate TLE1. miR‑664b‑3p was negatively modulated by RASSF8‑AS1; however, TLE1 was positively regulated by RASSF8‑AS1. Functionally, RASSF8‑AS1 acted as a ceRNA to upregulate TLE1 by sponging miR‑664b‑3p. In conclusion, the RASSF8‑AS1/miR‑664b‑3p/TLE1 axis acts by suppressing LSCC progression and may provide a novel insight for the molecular mechanism of LSCC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3892/or.2020.7771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7551431PMC
November 2020

Toward a Quantitative Relationship between Nanoscale Spatial Organization and Hybridization Kinetics of Surface Immobilized Hairpin DNA Probes.

ACS Sens 2021 02 2;6(2):371-379. Epub 2020 Oct 2.

Department of Nanoscience, University of North Carolina at Greensboro, Greensboro, North Carolina 27401, United States.

Hybridization of DNA probes immobilized on a solid support is a key process for DNA biosensors and microarrays. Although the surface environment is known to influence the kinetics of DNA hybridization, so far it has not been possible to quantitatively predict how hybridization kinetics is influenced by the complex interactions of the surface environment. Using spatial statistical analysis of probes and hybridized target molecules on a few electrochemical DNA (E-DNA) sensors, functioning through hybridization-induced conformational change of redox-tagged hairpin probes, we developed a phenomenological model that describes how the hybridization rates for single probe molecules are determined by the local environment. The predicted single-molecule rate constants, upon incorporation into numerical simulation, reproduced the overall kinetics of E-DNA sensor surfaces at different probe densities and different degrees of probe clustering. Our study showed that the nanoscale spatial organization is a major factor behind the counterintuitive trends in hybridization kinetics. It also highlights the importance of models that can account for heterogeneity in surface hybridization. The molecular level understanding of hybridization at surfaces and accurate prediction of hybridization kinetics may lead to new opportunities in development of more sensitive and reproducible DNA biosensors and microarrays.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1021/acssensors.0c01278DOI Listing
February 2021

Reliability of d-Dimer Determination in Diagnosis of Peri-Prosthetic Joint Infection: A Systematic Review and Meta-Analysis.

Surg Infect (Larchmt) 2021 May 8;22(4):374-382. Epub 2020 Sep 8.

Department of Joint Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.

Surgeons continue to seek indicators for the diagnosis of peri-prosthetic joint infection (PJI), which is a serious complication after total joint arthroplasty (TJA). Many recent studies have assessed the value of d-dimer in diagnosing PJI because of the close relation between the d-dimer value and inflammation. However, the conclusions from different studies are still disputed. We searched for studies published from 2011 to March 2020 using online databases and screened studies based on the inclusion criteria. Diagnostic parameters of d-dimer, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) were calculated, including the pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR) and the area under the curve (AUC). In addition, univariate meta-regression and subgroup analyses were performed to identify sources of heterogeneity. A total of nine studies with 431 Patients with PJI were included. The pooled sensitivity, specificity, DOR, and AUC of d-dimer were 0.82 (95% confidence interval [CI], 0.73-0.89), 0.73 (95% CI, 0.58-0.83), 12 (95% CI, 5-30), and 0.85 (95% CI, 0.82-0.88), respectively. In addition, the sensitivity, specificity, and AUC of CRP were 0.78 (95% CI, 0.73-0.83), 0.80 (95% CI, 0.73-0.86) and 0.85 (95% CI, 0.81-0.87), respectively, whereas those of ESR were 0.68 (95% CI, 0.60-0.74), 0.83 (95% CI, 0.75-0.88), and 0.80 (95% CI, 0.76-0.83), respectively. d-dimer determination had similar performance to CRP and ESR in the diagnosis of PJI and may be a good addition to the current diagnostic criteria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/sur.2020.212DOI Listing
May 2021

MiR-200b in heme oxygenase-1-modified bone marrow mesenchymal stem cell-derived exosomes alleviates inflammatory injury of intestinal epithelial cells by targeting high mobility group box 3.

Cell Death Dis 2020 06 25;11(6):480. Epub 2020 Jun 25.

Department of Organ Transplantation, Tianjin First Central Hospital, 300192, Tianjin, P.R. China.

Heme Oxygen-1 (HO-1)-modified bone marrow mesenchymal stem cells (BMMSCs) are effective to protect and repair transplanted small bowel and intestinal epithelial cells (IECs); however, the mechanism and the role of HO-1/BMMSCs-derived exosomes is unclear. In the present study, we aimed to verify that exosomes from a HO-1/BMMSCs and IEC-6 cells (IEC-6s) co-culture system could reduce the apoptosis of IEC-6s and decrease the expression of the tight junction protein, zona occludens 1, in the inflammatory environment. Using mass spectrometry, we revealed that high mobility group box 3 (HMGB3) and phosphorylated c-Jun NH2-terminal kinase (JNK), under the influence of differentially abundant proteins identified through proteomic analysis, play critical roles in the mechanism. Further studies indicated that microRNA miR-200b, which was upregulated in exosomes derived from the co-culture of HO-1/BMMSCs and IEC-6s, exerted its role by targeting the 3' untranslated region of Hmgb3 in this biological process. Functional experiments confirmed that miR-200b overexpression could reduce the inflammatory injury of IEC-6s, while intracellular miR-200b knockdown could significantly block the protective effect of HO-1/BMMSCs exosomes on the inflammatory injury of IEC-6s. In addition, the level of miR-200b in cells and exosomes derived from HO-1/BMMSCs stimulated by tumor necrosis factor alpha was significantly upregulated. In a rat small bowel transplantation model of allograft rejection treated with HO-1/BMMSCs, we confirmed that the level of miR-200b in the transplanted small bowel tissue was increased significantly, while the level of HMGB3/JNK was downregulated significantly. In conclusion, we identified that exosomes derived from HO-1/BMMSCs play an important role in alleviating the inflammatory injury of IECs. The mechanism is related to miR-200b targeting the abnormally increased expression of the Hmgb3 gene in IECs induced by inflammatory injury. The reduced level of HMGB3 then decreases the inflammatory injury.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41419-020-2685-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7316799PMC
June 2020

Heme oxygenase-1-modified bone marrow mesenchymal stem cells combined with normothermic machine perfusion to protect donation after circulatory death liver grafts.

Stem Cell Res Ther 2020 06 5;11(1):218. Epub 2020 Jun 5.

Department of Organ Transplantation, Tianjin First Central Hospital, No. 24 Fukang Road, Nankai District, Tianjin, 300192, People's Republic of China.

Background: Donation after circulatory death (DCD) liver grafts have a poor prognosis after transplantation. We investigated whether the outcome of DCD donor organs can be improved by heme oxygenase 1 (HO-1)-modified bone marrow-derived mesenchymal stem cells (BMMSCs) combined with normothermic machine perfusion (NMP), and explored its underlying mechanisms.

Methods: BMMSCs were isolated, cultured, and transduced with the HO-1 gene. An NMP system was established. DCD rat livers were obtained, preserved by different methods, and the recipients were divided into 5 groups: sham operation, static cold storage (SCS), NMP, BMMSCs combined with NMP, and HO-1/BMMSCs combined with NMP (HBP) groups. Rats were sacrificed at 1, 7, and 14 days after surgery; their blood and liver tissue samples were collected; and liver enzyme and cytokine levels, liver histology, high-mobility group box 1 (HMGB1) levels in monocytes and liver tissues, and expression of Toll-like receptor 4 (TLR4) pathway-related molecules were evaluated.

Results: After liver transplantation, the SCS group showed significantly increased transaminase levels, liver tissue damage, and shorter survival time. The HBP group showed lower transaminase levels, intact liver morphology, prolonged survival time, and decreased serum and liver proinflammatory cytokine levels. In the NMP and SCS groups, HMGB1 expression in the serum, monocytes, and liver tissues and TLR4 pathway-related molecule expression were significantly decreased.

Conclusions: HO-1/BMMSCs combined with NMP exerted protective effects on DCD donor liver and significantly improved recipient prognosis. The effect of HO-1/BMMSCs was greater than that of BMMSCs and was mediated via HMGB1 expression and TLR4 pathway inhibition.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13287-020-01736-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7275432PMC
June 2020

Nomograms to predict 2-year overall survival and advanced schistosomiasis-specific survival after discharge: a competing risk analysis.

J Transl Med 2020 05 6;18(1):187. Epub 2020 May 6.

Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Avenue, Wuhan, Hubei, 430030, China.

Background: The prognosis of patients with advanced schistosomiasis is poor. Pre-existing prognosis studies did not differentiate the causes of the deaths. The objectives were to evaluate the 2-year overall survival (OS) and advanced schistosomiasis-specific survival (ASS) in patients with advanced schistosomiasis after discharge through competing risk analysis and to build predictive nomograms.

Methods: Data was extracted from a previously constructed database from Hubei province. Patients were enrolled from September 2014 to January 2015, with follow up to January 2017. OS and ASS were primary outcome measures. Nomograms for estimating 2-year OS and ASS rates after discharge were established based on univariate and multivariate Cox regression model and Fine and Gray's model. Their predictive performances were evaluated using C-index and validated in both internal and external validation cohorts.

Results: The training cohort included 1487 patients with advanced schistosomiasis. Two-year mortality rate of the training cohort was 8.27% (123/1487). Competing events accounted for 26.83% (33/123). Older age, splemomegaly clinical classification, abnormal serum DBil, AST, ALP and positive HBsAg were significantly associated with 2-year OS. Older age, splemomegaly clinical classification, abnormal serum AST, ALP and positive HBsAg were significantly associated with 2-year ASS. The established nomograms were well calibrated, and had good discriminative ability, with a C-index of 0.813 (95% CI 0.803-0.823) for 2-year OS prediction and 0.834 (95% CI 0.824-0.844) for 2-year ASS prediction. Their predictive performances were well validated in both internal and external validation cohorts.

Conclusion: The effective predictors of 2-year OS and ASS were discovered through competing risk analysis. The nomograms could be used as convenient predictive tools in clinical practice to guide follow-up and aid accurate prognostic assessment.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s12967-020-02353-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201698PMC
May 2020

Bone marrow mesenchymal stem cells combine with normothermic machine perfusion to improve rat donor liver quality-the important role of hepatic microcirculation in donation after circulatory death.

Cell Tissue Res 2020 Aug 29;381(2):239-254. Epub 2020 Apr 29.

Department of Organ Transplantation, Tianjin First Central Hospital, No. 24 Fukang Road, Nankai District, Tianjin, 300192, People's Republic of China.

Donation after circulatory death (DCD) can expand the donor pool effectively. A gap remains in outcome between DCD livers and living donor livers, warranting improved DCD liver quality and urgent resolution. Bone marrow mesenchymal stem cells (BMMSCs) can regulate immunity, participate in the anti-inflammatory response, and secrete cytokines. We investigated the effect of BMMSCs combined with normothermic machine perfusion (NMP) on DCD liver quality, and the role of microcirculation therein. Rat thoracic aortas were clipped to obtain DCD livers, and a rat NMP system was established. The DCD livers were grouped by preservation method: normal, static cold storage (SCS), NMP (P), and BMMSCs plus NMP (BP); storage time was up to 8 h. Liver function in outflow perfusate was detected by biochemical methods; liver tissue histopathology was observed by hematoxylin-eosin staining; hepatocyte ultrastructure was observed by transmission electron microscopy; hepatocyte apoptosis was detected by terminal deoxynucleotidyl transferase dUTP nick end labeling; liver microcirculation-related indicators were detected by immunofluorescence, immunohistochemistry, Western blotting, and enzyme-linked immunosorbent assay. Compared with SCS, P and BP significantly improved liver function and liver histological damage, reduced hepatocyte apoptosis, and repaired hepatocyte mitochondrial damage after 6 h in vitro. BP also significantly inhibited intrahepatic macrophage activation and intercellular adhesion, improved endothelial damage, and significantly improved endothelin 1-nitric oxide balance and microcirculation perfusion. In conclusion, BP can improve DCD liver microcirculation and quality. The mechanism may be the improvement of improve hepatic sinusoidal endothelial injury and microcirculation perfusion by inhibiting macrophage activation and intercellular adhesion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00441-020-03202-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7369267PMC
August 2020

Neuroprotective efficacy of different levels of high-frequency repetitive transcranial magnetic stimulation in mice with CUMS-induced depression: Involvement of the p11/BDNF/Homer1a signaling pathway.

J Psychiatr Res 2020 06 5;125:152-163. Epub 2020 Apr 5.

Department of Neurology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No.1095 Jiefang Road, Wuhan, 430030, China. Electronic address:

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) is widely used to treat depression. However, the underlying mechanism has not been identified, and there is uncertainty regarding the optimal choice of stimulus parameters, especially stimulus frequency. Our previous study in mice demonstrated that 10-Hz HF-rTMS ameliorated depression by inducing expression of Homer1a and reducing excitability of cortical pyramidal cells. The aims of this study were to compare the effects of 15-Hz and 25-Hz HF-rTMS in a model of chronic unpredictable mild stress (CUMS)-induced depression and investigate its possible molecular mechanism. Male C57BL/6J mice were treated with CUMS for 28 days followed by 15-Hz and 25-Hz rTMS for 4 weeks. The sucrose preference, open field, forced swimming, and tail suspension tests were used to evaluate depression-like behaviors. Immunostaining was performed to measure neuronal loss and neurogenesis. Apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. Expression of synapse-related proteins and the effects of HF-rTMS on the signaling pathway were examined using Western blot. The results showed that both 15-Hz and 25-Hz rTMS had significant antidepressant effects; 15-Hz rTMS seemed to be more effective than 25-Hz rTMS in preventing neuronal loss and promoting neurogenesis, while 25-Hz rTMS was superior to 15-Hz rTMS in facilitating synaptic plasticity. We also found that 15-Hz and 25-Hz rTMS markedly increased expression of p11, BDNF, Homer1a, and p-trkB proteins. These findings suggest that 15-Hz and 25-Hz HF-rTMS could exert neuroprotective effects to different degrees via multiple perspectives, which at least in part involve the p11/BDNF/Homer1a pathway.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.jpsychires.2020.03.018DOI Listing
June 2020

Normothermic Machine Perfusion Combined with Bone Marrow Mesenchymal Stem Cells Improves the Oxidative Stress Response and Mitochondrial Function in Rat Donation After Circulatory Death Livers.

Stem Cells Dev 2020 07 5;29(13):835-852. Epub 2020 May 5.

Department of Organ Transplantation, Tianjin First Central Hospital, Tianjin, People's Republic of China.

There is a need to improve the quality of donor liver from donation after circulatory death (DCD). The purpose of this study was to investigate the effects and mechanism of normothermic machine perfusion (NMP) combined with bone marrow mesenchymal stem cells (BMMSCs) on the oxidative stress and mitochondrial function in DCD livers. DCD livers were obtained, a rat NMP system was established, and BMMSCs were extracted and identified. The DCD livers were grouped by their preservation method: Normal, static cold storage (SCS), NMP (P), and NMP combined with BMMSCs (PB), and the preservation time was up to 8 h. An IAR20 cell oxidative stress injury model was established in vitro by simulating DCD oxidative stress injury and coculturing with BMMSCs for 6 h. Compared with SCS group, after 6 h in vitro, the PB and P groups had significantly improved liver function and liver histological damage, reduced hepatocyte apoptosis and oxidative stress, improved hepatocyte mitochondrial damage, and increased mitochondrial membrane potential. These indicators were significantly better in the PB group than in the P group. BMMSCs significantly inhibited reactive oxygen species release from the IAR20 cell oxidative stress model in vitro, ameliorated mitochondrial damage, and increased mitochondrial membrane potential level. BMMSCs also downregulated the JUN N-terminal kinase-nuclear factor kappa B (JNK-NF-κB) signaling pathway significantly in the IAR20 cell oxidative stress model and promoted AMP-activated protein kinase (AMPK) activation. We verified that NMP combined with BMMSCs also played the same role in the PB group. NMP combined with BMMSCs could improve liver quality by relieving oxidative stress injury and improving mitochondrial function in rat DCD livers. The mechanism of protective role might involve inhibiting the JNK-NF-κB pathway to reduce oxidative stress and promote AMPK activation, thereby reducing mitochondrial damage and increase mitochondrial function.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/scd.2019.0301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336881PMC
July 2020

Aberrant DNA hypermethylation-silenced LINC00886 gene accelerates malignant progression of laryngeal carcinoma.

Pathol Res Pract 2020 Apr 13;216(4):152877. Epub 2020 Feb 13.

Otolaryngology Head and Neck Surgery Department, The Second Hospital of Hebei Medical University, Shijiazhuang 050005, Hebei, China. Electronic address:

Background: Long noncoding RNAs (lncRNAs) play crucial role in formation and progression of tumors. DNA methylation has become increasingly recognized as a frequent event of epigenetic alterations and one of the primary mechanisms of gene inactivation. The research aims to investigate the biofunction of a novel lncRNA in LSCC.

Methods: qRT-PCR, BGS, and MSP methods were employed to measure the relative expression level and methylation status of LINC00886. Additionally, we examined the effects of LINC00886 on cells proliferation and invasion using LINC00886 over-expression. Nude mouse xenograft models were conducted to assess LINC00886 effects on LSCC growth in vivo. High-throughput sequencing technology and Western blot assay were carried out to have an in-depth study of the downstream target genes and signaling pathways in which LINC00886 may participate.

Results: The remarkable downregulation of LINC00886 was observed in tumor tissues and laryngeal cancer cell lines. The significant decrease of LINC00886 was correlated with pathological grade in LSCC tissues. The expression level of LINC00886 in laryngeal cancer cell lines was significantly reversed by 5-Aza-dC. The occurrence of aberrant methylation events in the LINC00886 TSS was more responsible for the down-expression of LINC00886. Over-expression of LINC00886 dramatically mitigated cell proliferation, migration, and invasion in vitro as well as suppressed tumor growth in vivo. LINC00886 may be associated with VEGFA/PI3K/AKT signaling pathways and epithelial-mesenchymal transition (EMT) process.

Conclusions: We provide the first evidence of the involvement of LINC00886 in laryngeal carcinoma, which was downregulated due to methylation of the promoter region and served as tumor suppressor genes. LINC00886 is expected to become a novel biomarker in laryngeal carcinoma.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2020.152877DOI Listing
April 2020