Publications by authors named "Zhen-hua Huang"

10 Publications

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CXCL12-mediated monocyte transmigration into brain perivascular space leads to neuroinflammation and memory deficit in neuropathic pain.

Theranostics 2021 1;11(3):1059-1078. Epub 2021 Jan 1.

Department of Physiology and Pain Research Center, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.

Emerging clinical and experimental evidence demonstrates that neuroinflammation plays an important role in cognitive impairment associated with neuropathic pain. However, how peripheral nerve challenge induces remote inflammation in the brain remains largely unknown. The circulating leukocytes and plasma C-X-C motif chemokine 12 (CXCL12) and brain perivascular macrophages (PVMs) were analyzed by flow cytometry, Western blotting, ELISA, and immunostaining in spared nerve injury (SNI) mice. The memory function was evaluated with a novel object recognition test (NORT) in mice and with Montreal Cognitive Assessment (MoCA) in chronic pain patients. The classical monocytes and CXCL12 in the blood, PVMs in the perivascular space, and gliosis in the brain, particularly in the hippocampus, were persistently increased following SNI in mice. Using the transgenic CCR2 and CX3CR1 mice, we discovered that at least some of the PVMs were recruited from circulating monocytes. The SNI-induced increase in hippocampal PVMs, gliosis, and memory decline were substantially prevented by either depleting circulating monocytes via intravenous injection of clodronate liposomes or blockade of CXCL12-CXCR4 signaling. On the contrary, intravenous injection of CXCL12 at a pathological concentration in naïve mice mimicked SNI effects. Significantly, we found that circulating monocytes and plasma CXCL12 were elevated in chronic pain patients, and both of them were closely correlated with memory decline. CXCL12-mediated monocyte recruitment into the perivascular space is critical for neuroinflammation and the resultant cognitive impairment in neuropathic pain.
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http://dx.doi.org/10.7150/thno.44364DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7738876PMC
July 2021

The protection of acute spinal cord injury by subarachnoid space injection of Danshen in animal models.

J Spinal Cord Med 2019 05 19;42(3):355-359. Epub 2018 Jun 19.

a Department of Microscopic Orthopaedic, Renmin Hospital , Hubei University of Medicine , Shiyan , Hubei , China.

Context/objective: Following acute spinal cord injury (ASCI) in rabbits, subarachnoid space injection of Danshen was performed to protect the neurological damage. In this study, we established rabbit models of spinal cord injury using a modified Allen's method.

Design: After the operation introducing the injuries, the rabbits were randomized into two different groups, control group (normal saline, NS) and Danshen, a component extracted from Chinese herb, treatment group. Each rabbit was supplied with either the drug or placebo at 0.3 ml/kg each day through subarachnoid cavity.

Setting: Rabbit model of acute spinal cord injury were used for the response to Danshen treatment.

Participants: Total 48 Chinese rabbits aged four∼ five months old provided by Experimental Animal Center of Hubei Province were used for this study.

Interventions: Danshen drug or placebo was administered via a silicon tube embedded under the spinal dura mater to administer the drugs into subarachnoid cavity.

Outcome Measures: After the treatment, damage indicators including cell apoptosis, morphological changes and oxidative damages were assessed.

Results: We found out that cell apoptosis was decreased after Danshen injection as determined by downregulation of apoptosis index (AI) by TUNEL analysis as well as propidium iodide (PI) percentage by FACS analysis. In the meanwhile, we observed cells after the treatment have increased numbers of BCL-2 positive cells, this indicated the antiapoptotic gene expression is increased after Danshen treatment. When we check the oxidative damage indicators, we found superoxide dismutase (SOD) was increased and malondiadehyde (MDA) levels were decreased after the treatment.

Conclusion: Danshen can protect ASCI through inhibition of oxidative damage in the injured cells and thus reduce the subsequent cell apoptosis in the spinal.
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http://dx.doi.org/10.1080/10790268.2018.1468583DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6522962PMC
May 2019

Exosomes-mediated transfer of long noncoding RNA ZFAS1 promotes gastric cancer progression.

J Cancer Res Clin Oncol 2017 Jun 11;143(6):991-1004. Epub 2017 Mar 11.

Jiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu University, 301 Xuefu Road, Zhenjiang, 212013, Jiangsu, China.

Background: ZFAS1 is a newly identified long noncoding RNA (lncRNA) that promotes tumor growth and metastasis. Exosomes mediate cellular communications in cancer by transmitting active molecules. The presence of ZFAS1 in the circulating exosomes and the roles of exosomal ZFAS1 in gastric cancer (GC) remains unknown. The aim of this study was to investigate the potential roles of exosomal ZFAS1 in GC.

Methods: The expression of ZFAS1 was examined in the tumor tissues, serum samples, serum exosomes of GC patients and cell lines using qRT-PCR. The correlation between ZFAS1 expression and the clinicopathological characteristics was analyzed. The characteristics of exosomes were identified using transmission electron microscope (TEM), Nanoparticle Tracking Analysis (NTA), and western blot. The biological roles of ZFAS1 in GC cell growth and mobility were investigated using cell counting, cell colony formation, and transwell migration assay. The potential mechanism of ZFAS1 was demonstrated using flow cytometry, western blot, and qRT-PCR.

Results: ZFAS1 expression was elevated in GC cells, tumor tissues, serum and serum exosomes of GC patients. The increased ZFAS1 expression was significantly correlated with lymphatic metastasis and TNM stage. ZFAS1 knockdown inhibited the proliferation and migration of GC cells by suppressing cell cycle progression, inducing apoptosis, and inhibiting epithelial-mesenchymal transition (EMT). On the contrary, ZFAS1 overexpression promoted the proliferation and migration of GC cells. Moreover, ZFAS1 was present in exosomes and could be transmitted by exosomes to enhance GC cell proliferation and migration.

Conclusion: ZFAS1 could be delivered by exosomes to promote GC progression, which suggests that ZFAS1 may serve as a potential diagnostic and prognostic biomarker for GC.
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http://dx.doi.org/10.1007/s00432-017-2361-2DOI Listing
June 2017

[Enrichment of Cd2+ and Hg2+ in Phascolosoma esculenta and their effects].

Ying Yong Sheng Tai Xue Bao 2015 Jun;26(6):1871-6

The accumulation of Cd2+ and Hg2+ in Phascolosoma esculenta and its effects on its growth and main nutrient components were investigated using atomic absorption spectrometer analysis and atomic fluorescence spectrometer examination. The results showed that within the experimental heavy metal concentrations, the amounts of Cd2+ and Hg2+ accumulated in the somatic muscles increased with increasing exposure time and reached their saturated levels at the end of the experiment. Exposure of higher heavy metal concentrations speeded up the accumulation of Cd2+ and Hg2+ and subsequently took less time to reach their saturated levels, which were greater than those of lower concentration groups. The rate of mass gain of P. esculenta decreased with increasing the heavy metal exposure concentrations. The combination exposure of Cd2+ and Hg2+ led to a significantly lower mass gain rate compared to those exposed to Cd2+ or Hg2+. The protein content of somatic muscles increased with the increase of exposure concentration and reached the maximum values at 0.05 and 0.02 mg · L(-1) for Cd2+ and Hg2+, respectively. After that, the protein content of somatic muscles began to decrease. The combined exposure of the two heavy metals showed similar effect trends but more significant impacts on the protein content of somatic muscles. The lipid content of somatic muscles decreased with increasing the concentration of Cd2+ or Hg2+ exposure, and the combination of Cd2+ and Hg2+ led to lower lipid content.
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June 2015

A novel recombinant fibrinogenase of Agkistrodon acutus venom protects against hyperacute rejection via degradation of complements.

Biochem Pharmacol 2013 Mar 23;85(6):772-9. Epub 2012 Nov 23.

Department of Pharmacology, Medical College, Ji-Nan University, 601 Huangpu Road, Guangzhou, Guangdong 510632, PR China.

Hyperacute rejection (HAR) is a main barrier in xenotransplantation, which is mediated by the combination of natural antibody to the xenograft and complement activation. Current therapies have focus on the inhibition of complement by development of complement inhibitor and transgenic animal organ. Here, we investigated the effects of rFII, a recombinant fibrinogenase from Agkistrodon acutus venom, on complement and HAR. The degradation effect of rFII on complement was tested by SDS-PAGE, CH50 examination, ELISA Kit and cofocal immunofluorescence microscopy in vitro and in vivo. An ex-vivo rat-to-human perfusion model and a vivo guinea-pig-to-rat heat HAR model were used to determine the protection of rFII against HAR. Our investigation indicated that rFII could significantly degrade human C5, C6, and C9, decrease the activity of complement, and inhibit the MAC deposition on HUVECs membrane in vitro. In addition, serum levels of C1q, C3 and C4 in rat were gradually reduced after infusion of rFII. Importantly, in an ex vivo rat-to-human perfusion model, the survival of rat hearts perfused with human serum treated with rFII (83.36 ± 16.63 min) were significantly longer than that of hearts perfused with fresh human serum(15.94 ± 4.75 min). At the time of 15 minutes after perfusion, functions of hearts added with 50 ug/ml rFII sustained well with heart rates at 283 ± 65.32 beats/minute and LVDP at 13.70 ± 5.45 Kpa, while that of hearts perfused with fresh human serum were severely damaged by HAR with heart rates at 107.77 ± 40.31 beats/minute and LVDP at 1.01 ± 0.83 Kpa. We also found that rFII significantly decreased the levels of C1q, C3 and C4 in human fresh serum perfusate. In a vivo guinea-pig-to-rat heat HAR model, the survival of rat hearts treated with rFII were significantly longer than that of hearts perfused with normal saline; and relieved heart damage by complete activation. Our finding demonstrates the anti-complement property of rFII and its protection against HAR, indicating that rFII might be as a potential therapeutic agent for xenotransplantation.
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http://dx.doi.org/10.1016/j.bcp.2012.11.012DOI Listing
March 2013

Effects of the combination of mask preconditioning with midazolam pretreatment on anxiety and mask acceptance during pediatric inhalational induction and postoperative mask fear in children.

Chin Med J (Engl) 2012 Jun;125(11):1908-14

Translational Medical Neuroscience Center and Department of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.

Background: Anxiety and fear frequently causes an aversion to applying a face mask and increases difficulty during pediatric induction. There is at present little study of this problem. Therefore, the aim of this study was to investigate the effect of the combination of mask preconditioning and midazolam pretreatment on mask acceptance during pediatric induction and on postoperative mask fear.

Methods: One hundred and sixty children were randomly assigned into four groups: the mask preconditioning group (MaG), the midazolam pretreatment group (MiG), the mask/midazolam combination group (Ma/MiG), and the saline group (SaG). The Modified Yale Preoperative Anxiety Scale (m-YPAS) was employed to assess the anxiety in the operation room (OR). A Mask Acceptance Score (MAS) was measured during inhalational induction and the incidence of mask fear (MAS ≤ 2) was evaluated postoperatively.

Results: The MaG and Ma/MiG groups had the highest mask acceptance scores but there were no differences between these two groups (P < 0.05). The average anxiety level of children entering the OR was much lower in the MaG and Ma/MiG groups than in the SaG group (P < 0.05). During induction, the anxiety level increased in the SaG and MaG groups but decreased in the MiG and Ma/MiG groups (P < 0.05). At the postoperative third day, the incidence of mask fears was as high as 23% in the SaG group, 15% in the MiG group, but only 2.5% in the MaG and Ma/MiG groups.

Conclusions: The single use of mask preconditioning has a better influence than midazolam for increasing mask acceptance during inhalational induction and reducing postoperative mask fear, reducing the anxiety level during induction, improving induction compliance and shortening the total mask time. A mask preconditioning and midazolam combination did not increase mask acceptance during inhalational induction, reduce mask fears postoperatively, improve induction compliance, nor shorten the total mask time. But it can better reduce the anxiety level during induction.
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June 2012

A novel fibrinogenase from Agkistrodon acutus venom protects against DIC via direct degradation of thrombosis and activation of protein C.

Biochem Pharmacol 2012 Oct 20;84(7):905-13. Epub 2012 Jun 20.

Department of Pharmacology, Zhongshan Medical College, SUN Yat-Sen University, Guangzhou 510080, China.

The incidence of disseminated intravascular coagulation (DIC), which leads to multiple organ dysfunction and high mortality, has remained constant in recent years. At present, treatments of DIC have focused on preventing cytokine induction, inhibiting coagulation processes and promoting fibrinolysis. Recent clinical trials have supported the use of antithrombin and activated protein C supplementation in DIC. To better understand the mechanism of treatment on DIC, we here report a novel fibrinogenase from Agkistrodon acutus (FIIa) that effectively protected against LPS-induced DIC in a rabbit model, and detected the tissue factors expression in HUVE cells after using FIIa. In vivo, administration of FIIa reduced hepatic and renal damage, increased the concentration of fibrinogen, the activities of protein C, the platelet count, APTT, PT, FDP, the level of AT-III and t-PA, decreased the level of PAI-1, and increased survival rate in LPS-induced DIC rabbits. In vitro experiments, we further confirmed that FIIa up-regulated the expression of t-PA and u-PA, down-regulated the expression of PAI-1, and directly activated protein C. Our findings suggest that FIIa could effectively protect against DIC via direct degradation of microthrombi and activation of protein C as well as provide a novel strategy to develop a single proteinase molecule for targeting the main pathological processes of this disease.
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http://dx.doi.org/10.1016/j.bcp.2012.06.011DOI Listing
October 2012

Preparation and characterization of nanoparticles based on histidine-hyaluronic acid conjugates as doxorubicin carriers.

J Mater Sci Mater Med 2012 Aug 12;23(8):1921-9. Epub 2012 May 12.

College of Marine Life Science, Ocean University of China, Qingdao, People's Republic of China.

Histidine-hyaluronic acid (His-HA) conjugates were synthesized using hyaluronic acid (HA) as a hydrophilic segment and histidine (His) as hydrophobic segment by 1-ethyl-3(3-dimethylaminopropyl)carbodiimide (EDC) mediated coupling reactions. The structural characteristics of the His-HA conjugates were investigated using (1)H NMR. His-HA nanoparticles (HH-NPs) were prepared based on His-HA conjugates, and the characteristics of HH-NPs were investigated using dynamic light scattering, transmission electron microscopy (TEM), scanning electron microscopy (SEM), and fluorescence spectroscopy. The particles were between 342 and 732 nm in size, depending on the degree of substitution (DS) of the His. TEM and SEM images indicated that the morphology of HH-NPs was spherical in shape. The critical aggregation concentrations of HH-NPs ranged from 0.034 to 0.125 mg/ml, which decreased with an increase in the DS of the His. Images of fluorescence microscopy indicate that HH-NPs were taken up by the cancer cell line (MCF-7), and significantly decreased by competition inhibition of free HA. From the cytotoxicity test, it was found that DOX-loaded HH-NPs exhibited similar dose and time-dependent cytotoxicity against MCF-7 cells with free DOX.
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http://dx.doi.org/10.1007/s10856-012-4665-8DOI Listing
August 2012

Preparation and characterization of nanoparticles based on hydrophobic alginate derivative as carriers for sustained release of vitamin D3.

J Agric Food Chem 2011 Mar 2;59(5):1962-7. Epub 2011 Feb 2.

College of Marine Life Sciences, Ocean University of China, Qingdao 266003, People's Republic of China.

Hydrophobic alginate derivative was prepared by modification of alginate by acid chloride reaction using oleoyl chloride without organic solvents. The conjugate of oleoyl alginate ester (OAE) was confirmed by FT-IR and (1)H NMR. The degree of substitution (DS) of OAE was determined by (1)H NMR, and it ranged from 0.84 to 3.85. In distilled water, OAE formed self-assembled nanoparticles at low concentrations in aqueous medium, and nanoparticles retained their structural integrity both in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF). The loading and release characteristics of nanoparticles based on OAE were investigated using vitamin D(3) as a model nutraceutical. As the concentration of vitamin D(3) increased, the loading capacity (LC) increased, whereas the loading efficiency (LE) decreased. Nanoparticles could release vitamin D(3) at a sustained rate in gastrointestinal fluid. These results revealed the potential of OAE nanoparticles as oral carriers for sustained release of vitamin D(3).
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http://dx.doi.org/10.1021/jf1020347DOI Listing
March 2011

Construction of HBV-specific ribozyme and its recombinant with HDV and their cleavage activity in vitro.

World J Gastroenterol 2000 Jun;6(3):377-380

AIM:To construct the recombinant of HDV cDNA and HBV specific ribozyme gene by recombinant PCR in order to use HDV as a transporting vector carrying HBV-specific ribozyme into liver cells for inhibiting the replication of HBV.METHODS:We separately cloned the ribozyme (RZ) gene and recombinant DVRZ (comprising HDV cDNA and HBV-specific ribozyme gene) into the downstream of T7 promoter of pTAdv-T vector and studied the in vitro cleavage activity of their transcripts (rRZ, rDVRZ) on target RNA (rBVCF) from in vitro transcription of HBV C gene fragment(BVCF).RESULTS:Both the simple (rRZ) and the recombinant ribozyme rDVRZ could efficiently catalyze the cleavage of target RNA (rBVCF) under different temperatures (37°, 42° and 55°) and Mg(2+) concentrations (10mmol/L, 15mmol/L and 20mmol/L) and their catalytic activity tended to increase as the temperature was rising. But the activity of rRZ was evidently higher than that of rDVRZ.CONCLUSION:The recombinant of HDV cDNA and ribozyme gene had the potential of being further explored and used in gene therapy of HBV infection.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688756PMC
http://dx.doi.org/10.3748/wjg.v6.i3.377DOI Listing
June 2000
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