Publications by authors named "Huazhang Zhu"

12 Publications

  • Page 1 of 1

Profiles of inflammation factors and inflammatory pathways around the peri-miniscrew implant.

Histol Histopathol 2021 Apr 9:18336. Epub 2021 Apr 9.

Department of Orthodontics, Stomatological Hospital, Southern Medical University, Guangzhou, China.

Background: Peri-miniscrew implant is a temporary assistant armamentarium for the treatment of severe malocclusion and complex tooth movement, the inflammation around it is the main reason for the failure of orthodontic treatment due to the implant loosening and falling out. Inflammation around the peri-miniscrew implant is associated with the release of pro-inflammatory cytokines. These pro-inflammatory cytokines, in turn, recruit immune cells (such as macrophages, dendritic cells, T cells, and B cells), which can produce and release inflammatory biomarkers, regulate the interaction between immune cells, periodontal ligament cells, osteoblasts, and so on. However, there is currently no effective clinical treatment plan to prevent inflammation around implants.

Purpose: To investigate the potentially essential factors in the inflammatory response around the peri-miniscrew implant and explore the signaling pathways involved.

Methods: Here, we review the studies focused on inflammatory biomarkers (Interleukins, tumor necrosis factor-α (TNF-α), receptor activator of NF-κB ligand (RANKL), matrix metalloproteinases (MMPs), and cellular adhesion molecules (CAMs)) in peri-miniscrew implant crevicular fluid (PMICF), as well as inflammatory signaling pathways (Wnt5a, JNK, Erk1/2, NF-κBp65 and TAB/TAK) in periodontal cells from 1998 to 2020.

Results: A literature search revealed TLR-2, TLR-4, LOX-1, and BMPs are involved in regulating ILs (IL-1β, IL-6, IL-8, and IL-17), TNF-α, RANKL, MMP-2, MMP-9 expression via JNK, Erk1/2, Wnt5a, NF-κBp65, OPN, and TAB/TAK signaling pathways. Among them, IL-1β and IL-6 are the critical inflammation factors in the signaling pathways inducing the inflammatory reaction surrounding implants. Besides, CAM-1 was also regulated by MMP-9 and IL-17.

Conclusion: There are considerable potential factors involving regulating inflammatory biomarkers on downstream signaling pathways in peri-minisrew implant crevicular fluid.

Clinical Significance: This review provides the substantiation of these cell factors and signaling pathways around peri-miniscrew implants, proposes more practical clinical therapeutic ideas and schemes for improving the stability and clinical efficacy of peri-miniscrew implants.
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http://dx.doi.org/10.14670/HH-18-336DOI Listing
April 2021

Activation of ATF4 triggers trabecular meshwork cell dysfunction and apoptosis in POAG.

Aging (Albany NY) 2021 03 10;13(6):8628-8642. Epub 2021 Mar 10.

State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, Guangdong, China.

Primary open angle glaucoma (POAG) is the leading cause of irreversible blindness. Dysfunction of the trabecular meshwork (TM), resulting in decreased outflow of aqueous humor and increased intraocular pressure (IOP), plays an important role in the pathogenesis of POAG. However, the underlying mechanisms still remain unclear. In this study, we demonstrated that the eIF2-α/ATF4/CHOP branch of unfolded protein response (UPR) was activated in human trabecular meshwork cells (HTMCs) upon tert-butyl hydroperoxide (TBHP) exposure. Inhibition of ATF4 ameliorated TBHP-induced apoptosis and inflammatory cytokine production, while ectopic expression of ATF4 increased the expression of endothelial leukocyte adhesion molecule (ELAM)-1 and IL-8 in HTMCs. Furthermore, we found that ATF4 inhibition reduced tunicamycin-induced caspase-3 activation, ROS production, ELAM-1 expression, and HTMCs phagocytosis impairment. By an study in mice, we showed that overexpression of ATF4 in the TM induced C/EBP homologous protein (CHOP) expression and TM cells apoptosis, contributing to inflammatory cytokine production, and probably IOP elevation. More importantly, upregulation of ATF4 and CHOP, and colocalization of ATF4 with ELAM-1 were found in the TM of POAG patients. These results suggest that ATF4 is a critical mediator of oxidative stress and ER stress-induced TM cell dysfunction and apoptosis in POAG.
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http://dx.doi.org/10.18632/aging.202677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8034903PMC
March 2021

Loss of β-catenin via activated GSK3β causes diabetic retinal neurodegeneration by instigating a vicious cycle of oxidative stress-driven mitochondrial impairment.

Aging (Albany NY) 2020 06 23;12(13):13437-13462. Epub 2020 Jun 23.

Department of Physiology, School of Basic Medical Sciences, Shenzhen University Health Sciences Center, Shenzhen, Guangdong, China.

Synaptic neurodegeneration of retinal ganglion cells (RGCs) is the earliest event in the pathogenesis of diabetic retinopathy. Our previous study proposed that impairment of mitochondrial trafficking by hyperphosphorylated tau is a potential contributor to RGCs synapse degeneration. However, other molecular mechanisms underlying mitochondrial defect in diabetic retinal neurodegeneration remain to be elucidated. Here, using a high-fat diet (HFD)-induced diabetic mouse model, we showed for the first time that downregulation of active β-catenin due to abnormal GSK3β activation caused synaptic neurodegeneration of RGCs by inhibiting ROS scavenging enzymes, thus triggering oxidative stress-driven mitochondrial impairment in HFD-induced diabetes. Rescue of β-catenin via ectopic expression of β-catenin with a recombinant adenoviral vector, or via GSK3β inhibition by a targeted si-, through intravitreal administration, abrogated the oxidative stress-derived mitochondrial defect and synaptic neurodegeneration in diabetic RGCs. By contrast, ablation of β-catenin by si-- abolished the protective effect of GSK3β inhibition on diabetic RGCs by suppression of antioxidant scavengers and augmentation of oxidative stress-driven mitochondrial lesion. Thus, our data identify β-catenin as a part of an endogenous protective system in diabetic RGCs and a promising target to develop intervention strategies that protect RGCs from neurodegeneration at early onset of diabetic retinopathy.
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http://dx.doi.org/10.18632/aging.103446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377872PMC
June 2020

Non-invasive 40-Hz Light Flicker Ameliorates Alzheimer's-Associated Rhythm Disorder via Regulating Central Circadian Clock in Mice.

Front Physiol 2020 24;11:294. Epub 2020 Apr 24.

Department of Physiology, School of Basic Medical Sciences, Shenzhen University Health Science Center, Shenzhen University, Shenzhen, China.

Alzheimer's disease (AD) patients often exhibit perturbed circadian rhythm with fragmented sleep before disease onset. This study was designed to evaluate the effect of a 40-Hz light flicker on circadian rhythm in an AD mouse model (APP/PS1). Locomotor rhythms recordings were conducted to examine the circadian clock rhythm in APP/PS1 mice. Molecular biology analyses, including western blot and real-time qPCR assays, were conducted to assess the changes in circadian locomotor output cycles kaput (CLOCK), brain and muscle arnt-like protein-1 (BMAL1), and period 2 (PER2). In addition to determining the direct effect of a 40-Hz light flicker on hypothalamic central clock, whole-cell voltage-clamp electrophysiology was employed to record individual neurons of suprachiasmatic nucleus (SCN) sections. The results reported herein demonstrate that a 40-Hz light flicker relieves circadian rhythm disorders in APP/PS1 mice and returns the expression levels of key players in the central circadian clock, including Clock, Bmal1, and Per2, to baseline. Moreover, the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in SCN neurons is significantly lower in APP/PS1 mice than in the control, and the amplitude of sIPSCs is decreased. Exposure to a 40-Hz light flicker significantly increases the sIPSC frequency in SCN neurons of APP/PS1 mice, with little effect on the amplitude. However, the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) are both unaffected by a 40-Hz light flicker. The data suggest that a 40-Hz light flicker can ameliorate AD-associated circadian rhythm disorders, presenting a new type of therapeutic treatment for rhythm disorders caused by AD.
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http://dx.doi.org/10.3389/fphys.2020.00294DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193101PMC
April 2020

The Protective Effect of Vanadium on Cognitive Impairment and the Neuropathology of Alzheimer's Disease in APPSwe/PS1dE9 Mice.

Front Mol Neurosci 2020 10;13:21. Epub 2020 Mar 10.

Shenzhen Key Laboratory of Marine Biotechnology and Ecology, College of Life Sciences and Oceanography, Shenzhen University, Shenzhen, China.

Alzheimer's disease (AD) is a widely distributed neurodegenerative disease characterized clinically by cognitive deficits and pathologically by formation of amyloid-β (Aβ) plaque and neurofibrillary tangles (NFTs) in the brain. Vanadium is a biological trace element that has a function to mimic insulin for diabetes. Bis(ethylmaltolato) oxidovanadium (IV) (BEOV) has been reported to have a hypoglycemic property, but its effect on AD remains unclear. In this study, BEOV was supplemented at doses of 0.2 and 1.0 mmol/L to the AD model mice APPSwe/PS1dE9 for 3 months. The results showed that BEOV substantially ameliorated glucose metabolic disorder as well as synaptic and behavioral deficits of the AD mice. Further investigation revealed that BEOV significantly reduced Aβ generation by increasing the expression of peroxisome proliferator-activated receptor gamma and insulin-degrading enzyme and by decreasing β-secretase 1 in the hippocampus and cortex of AD mice. BEOV also reduced tau hyperphosphorylation by inhibiting protein tyrosine phosphatase-1B and regulating the pathway of insulin receptor/insulin receptor substrate-1/protein kinase B/glycogen synthase kinase 3 beta. Furthermore, BEOV could enhance autophagolysosomal fusion and restore autophagic flux to increase the clearance of Aβ deposits and phosphorylated tau in the brains of AD mice. Collectively, the present study provides solid data for revealing the function and mechanism of BEOV on AD pathology.
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http://dx.doi.org/10.3389/fnmol.2020.00021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7077345PMC
March 2020

Correction: Bis(ethylmaltolato)oxidovanadium(iv) inhibited the pathogenesis of Alzheimer's disease in triple transgenic model mice.

Metallomics 2020 04;12(4):631

Shenzhen Key Laboratory of Marine Biotechnology and Ecology, College of Life Sciences and Oceanography, Shenzhen University, 518060 Shenzhen, China.

Correction for 'Bis(ethylmaltolato)oxidovanadium(iv) inhibited the pathogenesis of Alzheimer's disease in triple transgenic model mice' by Zhijun He et al., Metallomics, 2020, DOI: 10.1039/c9mt00271e.
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http://dx.doi.org/10.1039/d0mt90008gDOI Listing
April 2020

AQP1 suppression by ATF4 triggers trabecular meshwork tissue remodelling in ET-1-induced POAG.

J Cell Mol Med 2020 03 13;24(6):3469-3480. Epub 2020 Feb 13.

Department of Physiology, School of Basic Medical Sciences, School of Medicine, Shenzhen University, Shenzhen, China.

Primary open-angle glaucoma (POAG) is the second leading cause of irreversible blindness worldwide. Increased endothelin-1 (ET-1) has been observed in aqueous humour (AH) of POAG patients, resulting in an increase in the out-flow resistance of the AH. However, the underlining mechanisms remain elusive. Using established in vivo and in vitro POAG models, we demonstrated that water channel Aquaporin 1 (AQP1) is down-regulated in trabecular meshwork (TM) cells upon ET-1 exposure, which causes a series of glaucomatous changes, including actin fibre reorganization, collagen production, extracellular matrix deposition and contractility alteration of TM cells. Ectopic expression of AQP1 can reverse ET-1-induced TM tissue remodelling, which requires the presence of β-catenin. More importantly, we found that ET-1-induced AQP1 suppression is mediated by ATF4, a transcription factor of the unfolded protein response, which binds to the promoter of AQP1 and negatively regulates AQP1 transcription. Thus, we discovered a novel function of ATF4 in controlling the process of TM remodelling in ET-1-induced POAG through transcription suppression of AQP1. Our findings also detail a novel pathological mechanism and a potential therapeutic target for POAG.
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http://dx.doi.org/10.1111/jcmm.15032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7131939PMC
March 2020

Bis(ethylmaltolato)oxidovanadium(iv) inhibited the pathogenesis of Alzheimer's disease in triple transgenic model mice.

Metallomics 2020 04 23;12(4):474-490. Epub 2020 Jan 23.

Shenzhen Key Laboratory of Marine Biotechnology and Ecology, College of Life Sciences and Oceanography, Shenzhen University, 518060 Shenzhen, China.

Vanadium compounds have been reported to mimic the anti-diabetes effects of insulin on rodent models, but their effects on Alzheimer's disease (AD) have rarely been explored. In this paper, 9-month-old triple transgenic AD model mice (3×Tg-AD) received bis(ethylmaltolato)oxidovanadium(iv) (BEOV) at doses of 0.2 mmol L (68.4 μg mL) and 1.0 mmol L (342 μg mL) for 3 months. BEOV at both doses was found to improve contextual memory and spatial learning in AD mice. It also improved glucose metabolism and protected neuronal synapses in the AD brain, as evidenced respectively by F-labeled fluoro-deoxyglucose positron emission tomography (F-FDG-PET) scanning and by transmission electron microscopy. Inhibitory effects of BEOV on β-amyloid (Aβ) plaques and neuronal impairment in the cortex and hippocampus of fluorescent AD mice were visualized three-dimensionally by applying optical clearing technology to brain slices before confocal laser scanning microscopy. Western blot analysis semi-quantitatively revealed the altered levels of Aβ in the brains of wildtype, AD, and AD treated with 0.2 and 1.0 mmol L BEOV mice (70.3%, 100%, 83.2% and 56.8% in the hippocampus; 82.4%, 100%, 66.9% and 42% in the cortex, respectively). The mechanism study showed that BEOV increased the expression of peroxisome proliferator-activated receptor γ (PPARγ) (140%, 100%, 142% and 160% in the hippocampus; 167%, 100%, 124% and 133% in the cortex) to inactivate the JAK2/STAT3/SOCS-1 pathway and to block the amyloidogenesis cascade, thus attenuating Aβ-induced insulin resistance in AD models. BEOV also reduced protein tyrosine phosphatase 1B (PTP1B) expression (74.8%, 100%, 76.5% and 53.8% in the hippocampus; 71.8%, 100%, 94.2% and 81.8% in cortex) to promote insulin sensitivity and to stimulate the PI3K/Akt/GSK3β pathway, subsequently reducing tau hyperphosphorylation (phosphorylated tau396 levels were 51.1%, 100%, 56.1% and 50.2% in the hippocampus; 22.2%, 100%, 36.1%, and 24% in the cortex). Our results suggested that BEOV reduced the pathological hallmarks of AD by targeting the pathways of PPARγ and PTP1B in 3×Tg AD mice.
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http://dx.doi.org/10.1039/c9mt00271eDOI Listing
April 2020

GSK3β-mediated tau hyperphosphorylation triggers diabetic retinal neurodegeneration by disrupting synaptic and mitochondrial functions.

Mol Neurodegener 2018 11 22;13(1):62. Epub 2018 Nov 22.

Department of Physiology, School of Basic Medical Sciences, Center for Diabetes, Obesity and Metabolism, Shenzhen University Health Sciences Center, Shenzhen, 518060, Guangdong, China.

Background: Although diabetic retinopathy (DR) has long been considered as a microvascular disorder, mounting evidence suggests that diabetic retinal neurodegeneration, in particular synaptic loss and dysfunction of retinal ganglion cells (RGCs) may precede retinal microvascular changes. Key molecules involved in this process remain poorly defined. The microtubule-associated protein tau is a critical mediator of neurotoxicity in Alzheimer's disease (AD) and other neurodegenerative diseases. However, the effect of tau, if any, in the context of diabetes-induced retinal neurodegeneration has yet to be ascertained. Here, we investigate the changes and putative roles of endogeneous tau in diabetic retinal neurodegeneration.

Methods: To this aim, we combine clinically used electrophysiological techniques, i.e. pattern electroretinogram and visual evoked potential, and molecular analyses in a well characterized high-fat diet (HFD)-induced mouse diabetes model in vivo and primary retinal ganglion cells (RGCs) in vitro.

Results: We demonstrate for the first time that tau hyperphosphorylation via GSK3β activation causes vision deficits and synapse loss of RGCs in HFD-induced DR, which precedes retinal microvasculopathy and RGCs apoptosis. Moreover, intravitreal administration of an siRNA targeting to tau or a specific inhibitor of GSK3β reverses synapse loss and restores visual function of RGCs by attenuating tau hyperphosphorylation within a certain time frame of DR. The cellular mechanisms by which hyperphosphorylated tau induces synapse loss of RGCs upon glucolipotoxicity include i) destabilizing microtubule tracks and impairing microtubule-dependent synaptic targeting of cargoes such as mRNA and mitochondria; ii) disrupting synaptic energy production through mitochondria in a GSK3β-dependent manner.

Conclusions: Our study proposes mild retinal tauopathy as a new pathophysiological model for DR and tau as a novel therapeutic target to counter diabetic RGCs neurodegeneration occurring before retinal vasculature abnormalities.
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http://dx.doi.org/10.1186/s13024-018-0295-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6251088PMC
November 2018

Sodium selenate activated Wnt/β-catenin signaling and repressed amyloid-β formation in a triple transgenic mouse model of Alzheimer's disease.

Exp Neurol 2017 11 13;297:36-49. Epub 2017 Jul 13.

College of Life Sciences & Oceanography, Shenzhen Key Laboratory of Marine Biotechnology and Ecology, Shenzhen University, Shenzhen 518060, China. Electronic address:

Accumulating evidences show that selenium dietary intake is inversely associated with the mortality of Alzheimer's disease (AD). Sodium selenate has been reported to reduce neurofibrillary tangles (NFT) in the tauopathic mouse models, but its effects on the Wnt/β-catenin signaling pathway and APP processing remain unknown during AD formation. In this paper, triple transgenic AD mice (3×Tg-AD) had been treated with sodium selenate in drinking water for 10month before the detection of hippocampal pathology. Increased Aβ generation, tau hyperphosphorylation and neuronal apoptosis were found in the hippocampus of AD model mouse. Down-regulation of Wnt/β-catenin signaling is closely associated with the alteration of AD pathology. Treatment with sodium selenate significantly promoted the activity of protein phosphatases of type 2A (PP2A) and repressed the hallmarks of AD. Activation of PP2A by sodium selenate could increase active β-catenin level and inhibit GSK3β activity in the hippocampal tissue and primarily cultured neurons of AD model mouse, leading to activation of Wnt/β-catenin signaling and transactivation of target genes, including positively-regulated genes c-myc, survivin, TXNRD2 and negatively-regulated gene BACE1. Meanwhile, APP phosphorylation was also reduced on the Thr668 residue after selenate treatment, causing the decreases of APP cleavage and Aβ generation. These findings reveal that the Wnt/β-catenin signaling is a potential target for prevention of AD and sodium selenate may be developed as a new drug for AD treatment.
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http://dx.doi.org/10.1016/j.expneurol.2017.07.006DOI Listing
November 2017

GLP1 protects cardiomyocytes from palmitate-induced apoptosis via Akt/GSK3b/b-catenin pathway.

J Mol Endocrinol 2015 Dec 18;55(3):245-62. Epub 2015 Sep 18.

School of MedicineShenzhen University Diabetes Center, Shenzhen University, Shenzhen 518060, ChinaDepartment of GeriatricShenzhen Second People's Hospital, First Affiliated Hospital of Shenzhen University, Shenzhen 518035, China.

Activation of apoptosis in cardiomyocytes by saturated palmitic acids contributes to cardiac dysfunction in diabetic cardiomyopathy. Beta-catenin (b-catenin) is a transcriptional regulator of several genes involved in survival/anti-apoptosis. However, its role in palmitate-induced cardiomyocyte apoptosis remains unclear. Glucagon-like peptide 1 (GLP1) has been shown to exhibit potential cardioprotective properties. This study was designed to evaluate the role of b-catenin signalling in palmitate-induced cardiomyocyte apoptosis and the molecular mechanism underlying the protective effects of GLP1 on palmitate-stressed cardiomyocytes. Exposure of neonatal rat cardiomyocytes to palmitate increased the fatty acid transporter CD36-mediated intracellular lipid accumulation and cardiomyocyte apoptosis, decreased accumulation and nuclear translocation of active b-catenin, and reduced expression of b-catenin target protein survivin and BCL2. These detrimental effects of palmitate were significantly attenuated by GLP1 co-treatment. However, the anti-apoptotic effects of GLP1 were markedly abolished when b-catenin was silenced with a specific short hairpin RNA. Furthermore, analysis of the upstream molecules and mechanisms responsible for GLP1-associated cardiac protection revealed that GLP1 restored the decreased phosphorylation of protein kinase B (Akt) and glycogen synthase kinase-3b (GSK3b) in palmitate-stimulated cardiomyocytes. In contrast, inhibition of Akt with an Akt-specific inhibitor MK2206 or blockade of GLP1 receptor (GLP1R) with a competitive antagonist exendin-(9-39) significantly abrogated the GLP1-mediated activation of GSK3b/b-catenin signalling, leading to increased apoptosis in palmitate-stressed cardiomyocytes. Collectively, our results demonstrated for the first time that the attenuated b-catenin signalling may contribute to palmitate-induced cardiomyocyte apoptosis, while GLP1 can protect cardiomyocytes from palmitate-induced apoptosis through activation of GLP1R/Akt/GSK3b-mediated b-catenin signalling.
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http://dx.doi.org/10.1530/JME-15-0155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621609PMC
December 2015

Microemulsion-based synthesis and electrochemical evaluation of different nanostructures of LiCoO2 prepared through sacrificial nanowire templates.

Nanoscale 2014 Jan;6(2):860-6

School of Chemical Engineering, Purdue University, 480 Stadium Mall Drive, West Lafayette, IN 47907, USA.

For the first time, we demonstrate the use of a microemulsion reaction to synthesize different nanostructures of LiCoO2 cathode material. By varying the annealing temperature and time, porous nanowires and nanoparticles of LiCoO2 are obtained. The electrochemical performances of these different nanostructures obtained under the respective annealing conditions are evaluated. It is shown that nanoparticles formed under the annealing condition of 700 °C, 1.5 h perform the best, delivering an initial capacity of around 135 mA h g(-1), which is close to the theoretical capacity of LiCoO2, 140 mA h g(-1). They also exhibit a capacity retention of around 93% by 100 cycles at 0.1 C. Comparisons are made between our LiCoO2 material obtained under different annealing conditions and those in the literature.
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http://dx.doi.org/10.1039/c3nr05243eDOI Listing
January 2014