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PubMed | Hubei University and Affiliated Hospital of Guangdong Medical University
Type: Journal Article | Journal: Molecular brain | Year: 2016

Endothelial cell (EC) released microvesicles (EMVs) can affect various target cells by transferring carried genetic information. Astrocytes are the main components of the blood brain barrier (BBB) structure in the brain and participate in regulating BBB integrity and blood flow. The interactions between ECs and astrocytes are essential for BBB integrity in homeostasis and pathological conditions. Here, we studied the effects of human brain microvascular ECs released EMVs on astrocyte functions. Additionally, we investigated the effects of EMVs treated astrocytes on regulating BBB function and cerebral ischemic damage.EMVs prepared from ECs cultured in normal condition (n-EMVs) or oxygen and glucose deprivation (OGD-EMVs) condition had diverse effects on astrocytes. The n-EMVs promoted, while the OGD-EMVs inhibited the proliferation of astrocytes via regulating PI3K/Akt pathway. Glial fibrillary acidic protein (GFAP) expression (marker of astrocyte activation) was up-regulated by n-EMVs, while down-regulated by OGD-EMVs. Meanwhile, n-EMVs inhibited but OGD-EMVs promoted the apoptosis of astrocytes accompanied by up/down-regulating the expression of Caspase-9 and Bcl-2. In the BBB model of ECs-astrocytes co-culture, the n-EMVs, conversely to OGD-EMVs, decreased the permeability of BBB accompanied with up-regulation of zonula occudens-1(ZO-1) and Claudin-5. In a transient cerebral ischemia mouse model, n-EMVs ameliorated, while OGD-EMVs aggravated, BBB disruption, local cerebral blood flow (CBF) reduction, infarct volume and neurological deficit score.Our data suggest that EMVs diversely modulate astrocyte functions, BBB integrity and CBF, and could serve as a novel therapeutic target for ischemic stroke.

Shian H.,Affiliated Hospital of Guangdong Medical University
National Medical Journal of China | Year: 2016

Objective To investigate expression changes and role of Gα11 protein in the processes of muscularization of non-muscular pulmonary7 arterioles and effect of sildenafil intervention in rats with pulmonary arterial hypertension (PAH). Methods Thirty SD rats were randomly divided into three groups, including normal control group, monocrotaline (MCT) group and sildenafil group; PAH model was prepared with 50 mg/kg MCT treatment for 4 weeks in the MCT group, and these rats were treated by 25 mg/kg sildenafil for 2 weeks after PAH formation in the sildenafil group, and the normal control group were treated with the equal amounts ot physiological saline instead of monocrotaline; pulmonary artery pressure was measured with jugular vein catheterization; hematoxylin and eosin (HE) staining method was used to detect the pulmonary arteriolar morphology and vascular tissue parameters; expression of the target Gall protein, vascular smooth muscle marker osteopontin (OPN) and proliferation marker proliferating cell nuclear antigen (PCNA) was detected by Western blot. Results Pulmonary artery mean pressure (mPAP), non-muscular pulmonary arterioles wall thickness index (TI) and area index (Al) of the MCT group were higher than those of the normal control group [ (27. 43 ± 3. 97) vs (11. 93 ± 1. 52) mmHg (1 mmHg =0. 133 kPa), 0. 49 ± 0. 07 vs 0. 31 ± 0. 09 and 0. 74 ± 0. 05 vs 0. 45 ± 0. 10 ] (all P < 0. 05), and meanwhile the expression levels of Gal 1 and the related proteins including OPN and PCNA were significantly enhanced. mPAP, TI and AI[ (18. 59 ± 1. 44) mmHg, 0. 39 ±0. 09 and 0. 56 ±0. 04] of the sildenafil group were all lower than those of the MCT group (all P <0. 05), and furthermore, expressions of Gal 1, OPN and PCNA also reduced in line with these changes. Conclusion Gal 1 protein plays a role in the development of PAH and pulmonary non-muscular arteriole muscularization, and sildenafil effectively suppresses PAH and pulmonary vascular remodeling by inhibiting Gαll expression.

PubMed | Affiliated Hospital of Guangdong Medical University, Guangdong Provincial Peoples Hospital, Southern Medical University and Guangdong Medical University
Type: | Journal: Drug design, development and therapy | Year: 2016

To investigate the bone-protective effects of salvianolate (Sal), a total polyphenol from Radix Salviae miltiorrhizae, on bone tissue in the spontaneous lupus-prone mouse model, B6.MRL-Fas (lpr) /J, undergoing glucocorticoid (GC) treatment.Fifteen-week-old female B6.MRL-Fas (lpr) /J mice were administered either a daily dose of saline (lupus group), prednisone 6 mg/kg (GC group), Sal 60 mg/kg (Sal group); or GC plus Sal (GC + Sal group) for a duration of 12 weeks. Age-matched female C57BL/6J wild-type (WT) mice were used for control. Micro-computed tomography assessments, bone histomorphometry analysis, bone biomechanical test, immunohistochemistry and immunoblotting analysis for bone markers, and renal histology analysis were performed to support our research endeavor.Lupus mice developed a marked bone loss and deterioration of mechanical properties of bone due to an increase in bone resorption rather than suppression of bone formation. GC treatment strongly inhibited bone formation in lupus mice. Sal treatment significantly attenuated osteogenic inhibition, and also suppressed hyperactive bone resorption, which recovered the bone mass and mechanical properties of bone in both the untreated and GC-treated lupus mice.The data support further preclinical investigation of Sal as a potential therapeutic strategy for the treatment of systemic lupus erythematosus-related bone loss.

PubMed | Affiliated Hospital of Guangdong Medical University
Type: Comparative Study | Journal: International journal of dermatology | Year: 2016

Lichen striatus (LS) and linear lichen planus (LLP) are separate uncommon disorders belonging to linear inflammatory dermatoses. The immunotyping of inflammatory cells has been investigated in LS and lichen planus (LP), but epidermal proliferation and differentiation have little been described in LS and LLP.The clinical and pathological data of eight patients with LS and seven with LLP were retrospectively collected. Immunotyping of infiltrated cells and expression of Ki-67, K16, involucrin, and filaggrin were stained by immunohistochemistry in skin lesions of these patients and normal skin of eight healthy controls.Dermal infiltrates contained primarily CD3+ and CD68+ cells in three groups. CD4+ cells were predominantly located in the perivascular area, while CD8+ cells were frequently close to the junctional zone. Compared with control skin, epidermal and dermal CD1a+ cells, and dermal CD3+, CD4+, CD8+, and CD68+ cells were increased in LS and LLP (P < 0.05), while Ki-67+ cells were significantly high in LLP (P < 0.05) but not in LS. K16 and involucrin expression in LLP were more extensive than in LS, and filaggrin expression was similar between both entities.Our results indicate that the predominance of CD8+ cells and increased epidermal proliferation and abnormal keratinization are present in both dermatoses, although the levels of the above indexes are mild in LS as compared to LLP. These two entities might be due to the interaction of infiltrated cells and keratinocytes, and CD8+ cells could play a pivotal role in their pathogenesis.

PubMed | Affiliated Hospital of Guangdong Medical University
Type: Journal Article | Journal: Biological & pharmaceutical bulletin | Year: 2016

Many anti-epileptic drugs (AEDs) that mainly target ion channels or post-synaptic receptors are in clinical use, but a proportion of patients are resistant to these traditional AEDs and experience repeated severe break-out seizures. Given its involvement in the etiology of epilepsy, the neurotransmitter glycine may serve as a novel target for epilepsy treatment. Increasing evidence suggests that inhibitors of glycine transporter 1 (GlyT1) exhibit anti-seizure properties in mouse models and show potential as anti-convulsions drugs. In the present study, we investigated the effect of a highly selective GlyT1 inhibitor (named M22) on glycine transport kinetics using a radioactive substrate uptake assay and investigated the anti-seizure effects of M22 on the maximal electroshock seizure threshold (MEST) test and the timed intravenous (i.v.) pentylenetetrazole (PTZ) intravenous test. Our results demonstrate that M22 was capable of elevating the seizure threshold in the MEST test but did not alter the seizure threshold in the PTZ i.v. test. Strychnine, an inhibitor of glycine receptor activity, reversed the threshold elevation at a subconvulsive dosage (0.1mg/kg subcutaneously) in the MEST test and did not affect M22 plasma levels in mice, suggesting that the anti-seizure effect in this model may be mediated by increased glycine receptor activity. Moreover, M22 administration did not influence motor function and coordination in mice. In combination with the previously reported excellent pharmacokinetic features of M22, our present results suggested that M22 has the potential to serve as a new anti-convulsive drug or as a lead compound for the development of AEDs.

PubMed | Affiliated Hospital of Guangdong Medical University
Type: | Journal: Stem cells international | Year: 2016

We evaluated the efficacy of platelet-rich plasma (PRP) in combination with allogeneic bone marrow mesenchymal stem cells (BMSCs) for the treatment of osteoporotic bone defects in an ovariectomized rat model. By day 42 after injury,

PubMed | Affiliated Hospital of Guangdong Medical University, Guangdong Medical University and Southern Medical University
Type: Journal Article | Journal: Acta pharmacologica Sinica | Year: 2016

Our previous studies show that salvianolic acid B (Sal B) promotes osteoblast differentiation and matrix mineralization. In this study, we evaluated the protective effects of Sal B on the osteogenesis in dexamethasone (Dex)-treated larval zebrafish, and elucidated the underlying mechanisms.At 3 d post fertilization, wild-type AB zebrafish larvae or bone transgenic tg (sp7:egfp) zebrafish larvae were exposed to Sal B, Dex, or a mixture of Dex+Sal B for 6 d. Bone mineralization in AB strain larval zebrafish was assessed with alizarin red staining, and osteoblast differentiation in tg (sp7:egfp) larval zebrafish was examined with fluorescence scanning. The expression of osteoblast-specific genes in the larvae was detected using qRT-PCR assay. The levels of oxidative stress markers (ROS and MDA) in the larvae were also measured.Exposure to Dex (5-20 mol/L) dose-dependently decreased the bone mineralization area and integral optical density (IOD) in wild-type AB zebrafish larvae and the osteoblast fluorescence area and IOD in tg (sp7:egfp) zebrafish larvae. Exposure to Dex (10 mol/L) significantly reduced the expression of osteoblast-specific genes, including runx2a, osteocalcin (OC), alkaline phosphatase (ALP) and osterix (sp7), and increased the accumulation of ROS and MDA in the larvae. Co-exposure to Sal B (0.2-2 mol/L) dose-dependently increased the bone mineralization area and IOD in AB zebafish larvae and osteoblast fluorescence in tg (sp7:egfp) zebrafish larvae. Co-exposure to Sal B (2 mol/L) significantly attenuated deleterious alterations in bony tissue and oxidative stress in both Dex-treated AB zebafish larvae and tg (sp7:egfp) zebrafish larvae.Sal B stimulates bone formation and rescues GC-caused inhibition on osteogenesis in larval zebrafish by counteracting oxidative stress and increasing the expression of osteoblast-specific genes. Thus, Sal B may have protective effects on bone loss trigged by GC.

PubMed | Affiliated Hospital of Guangdong Medical University
Type: | Journal: Mycopathologia | Year: 2017

To date, only one case of post-traumatic endophthalmitis caused by Scedosporium dehoogii has been reported, but its contamination or colonization might not be precluded due to the absence of pathogenic isolation and/or pathological examination. We report the first case to our knowledge of S. dehoogii-induced subcutaneous scedosporiosis in a psoriatic patient. A 58-year-old man with 5-year history of psoriasis vulgaris and immunosuppressant therapy developed pyrexia and multiple subcutaneous abscesses on both knees. Direct microscopy of the yellowish pus showed masses of bright green short spores. Skin biopsy revealed some branched septate hyphae within the granuloma. Two aspirated pus specimens collected at a 1-week interval produced white cottony colonies on Sabouraud dextrose agar. Bacterial cultures of one blood and two purulent samples were negative, and fungal culture of blood sample was not performed. The isolate was identified as S. dehoogii using -tubulin phylogeny and species-specific PCR with primer MSDE1/MSA2. Without addition of antifungal treatment, subcutaneous lesions disappeared spontaneously after immunosuppressant withdrawal and no relapse occurred during 64-month follow-up. The spontaneous recovery may result from immune reconstitution following immunosuppressant discontinuation.

PubMed | Guangdong Medical University and Affiliated Hospital of Guangdong Medical University
Type: Journal Article | Journal: Oncology letters | Year: 2017

Diosmetin (DIOS), a flavonoid compound, is abundant in Citrus limon. Emerging studies have shown that DIOS is an effective compound implicated in multiple types of cancer. However, whether DIOS serves a role in hepatocellular carcinoma (HCC) is still obscure. HepG2 cells were used in the present study, and it was observed that DIOS exhibited antitumor activity against liver cancer cells. Western blotting was performed to evaluate cell apoptosis and survival-associated proteins, and the results demonstrated that DIOS treatment resulted in the activation of the p53-dependent apoptosis pathway. Our results revealed that DIOS caused inhibition of the nuclear factor (NF)-B signaling pathway and downregulation of Notch3 receptor. Furthermore, by using small hairpin RNA-Notch3, it was confirmed that DIOS inhibited the NF-B signaling pathway by inactivation of Notch3. In conclusion, the present results demonstrated that DIOS triggered cell apoptosis by activation of the p53 signaling pathway and inhibited the NF-B cell survival pathway by downregulation of Notch3 receptor expression. DIOS is a potential agent for prevention of HCC.

PubMed | Affiliated Hospital of Guangdong Medical University
Type: Journal Article | Journal: Oncology letters | Year: 2017

Hepatocellular carcinoma (HCC), which is a type of malignant tumor, is the fifth most common cancer in men and ninth in women worldwide. The aim of the present study was to investigate the antitumor effect of diosmetin (DIOS) in hepatocellular carcinoma HepG2 cells. The proliferation, apoptosis and autophagy rates of HepG2 cells were measured following treatment with DIOS. The effects of DIOS treatment on HepG2 cell proliferation and apoptosis rates were analyzed using MTT assays and Annexin V staining, respectively. The effect of DIOS treatment on autophagy levels was assessed using transmission electron microscopy, green fluorescent protein (GFP)-microtubule-associated protein 1 light chain (LC3) transfection and LysoTracker Red staining. Furthermore, bafilomycin A1 (BA1), an autophagy inhibitor, was used to assess the association between DIOS and cell autophagy, proliferation and apoptosis. In addition, the expression of autophagy-related proteins [mammalian target of rapamycin (mTOR), phosphatidylinositol 3-kinase, P70S6K, phosphoinositide-dependent kinase-1, extracellular signal-regulated kinase, 5-AMP-activated protein kinase and Akt] and apoptosis-related proteins [B-cell lymphoma (Bcl)-2-associated X protein, Bak, p53, Bcl-2 and caspase-3] were analyzed by western blotting. The results revealed that DIOS significantly inhibited proliferation (P<0.01) and induced apoptosis (P<0.001) in HepG2 cells. It was also demonstrated that DIOS triggered autophagy by regulating the mTOR pathway in HepG2 cells. Notably, following treatment of HepG2 cells with the autophagy inhibitor, BA1, the expression of apoptosis-related proteins, including Bax, Bak and p53, were significantly decreased (P<0.05), and cell viability was recovered to a certain extent. In conclusion, DIOS inhibits cell proliferation and induces apoptosis in HepG2 cells via regulation of the mTOR pathway. Thus, the results of the current study indicate that DIOS may present a potential therapeutic agent for HCC treatment.

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