Chong-Gang Pei

Disturbed spontaneous brain activity pattern in patients with primary angle-closure glaucoma using amplitude of low-frequency fluctuation: a fMRI study

Objective The aim of this study is to use amplitude of low-frequency fluctuation (ALFF) as a method to explore the local features of spontaneous brain activity in patients with primary angle -closure glaucoma (PACG) and ALFFs relationship with the behavioral performances. Methods A total of twenty one patients with PACG (eight males and 13 females), and twenty one healthy subjects (nine males and twelve females) closely matched in age, sex, and education, each underwent a resting-state functional magnetic resonance imaging scan. The ALFF method was used to assess the local features of spontaneous brain activity. The correlation analysis was used to explore the relationships between the observed mean ALFF signal values of the different areas in PACG patients and the thickness of the retinal nerve fiber layer (RNFL). Results Compared with the healthy subjects, patients with PACG had significant lower ALFF areas in the left precentral gyrus, bilateral middle frontal gyrus, bilateral superior frontal gyrus, right precuneus, and right angular gyrus, and higher areas in the right precentral gyrus. In the PACG group, there were significant negative correlations between the mean ALFF signal value of the right middle frontal gyrus and the left mean RNFL thickness (r=−0.487, P=0.033), and between the mean ALFF signal value of the left middle frontal gyrus and the right mean RNFL thickness (r=−0.504, P=0.020). Conclusion PACG mainly involved in the dysfunction in the frontal lobe, which may reflect the underlying pathologic mechanism of PACG.

Rhamnazin, a novel inhibitor of VEGFR2 signaling with potent antiangiogenic activity and antitumor efficacy

Anti-angiogenesis targeting vascular endothelial growth factor receptor 2 (VEGFR2) has emerged as an important tool for cancer therapy. The identification of new drugs from natural products has a long and successful history. In this study, we described a novel VEGFR2 inhibitor, rhamnazin, which inhibits tumor angiogenesis and growth. Rhamnazin significantly inhibited proliferation, migration and tube formation of human umbilical vascular endothelial cells (HUVECs) in vitro as well as inhibited sprouts formation of rat aorta ring. In addition, it inhibited vascular endothelial growth factor (VEGF)-induced phosphorylation of VEGFR2 and its downstream signaling regulator in HUVECs. Moreover, rhamnazin could directly inhibit proliferation of breast cancer cells MDA-MB-231 in vitro and in vivo. Oral administration of rhamnazin at a dose of 200 mg/kg/day could markedly inhibited human tumor xenograft growth and decreased microvessel densities (MVD) in tumor sections. Taken together, these preclinical evaluations suggest that rhamnazin inhibits angiogenesis and may be a promising anticancer drug candidate.

Evaluation of novel decellularizing corneal stroma for cornea tissue engineering applications.

AIM To develop a new decellularization method depended upon the natural corneal structure and to harvest an ideal scaffold with good biocompatibilities for corneal reconstruction. METHODS The acellular cornea matrix (ACM) were prepared from de-epithelium fresh porcine corneas (DFPCs) by incubation with 100% fresh human sera and additional electrophoresis at 4°C. Human corneal epithelial cells (HCEs) were used for the cytotoxicity tests of ACM. ACM were implanted into the Enhanced Green Fluorecence Protein (eGFP) transgenic mouse anterior chamber for evaluation of histocompatibility. RESULTS HE and GSIB4 results showed fresh porcine cornea matrix with 100% human sera and electrophoresis could entirely decellularize stromal cell without reducing its transparency. ACM had no cytotoxic effect ex vivo. Animal test showed there was no rejection for one month after surgery. CONCLUSION These results provide a decellularizing approach for the study of corneal tissue engineering and had the broader implications for the field of biological tissue engineering in other engineered organ or tissue matrix.

Inhibition of miR-134 Protects Against Hydrogen Peroxide-Induced Apoptosis in Retinal Ganglion Cells

MicroRNAs (miRNAs) have been suggested to play an important role in neurological diseases. Particularly, miR-134 is reportedly involved in regulating neuron survival. However, the association between miR-134 and retinal ganglion cell (RGC) survival under adverse stimulus has not been extensively investigated. In this study, we aimed to explore the role and underlying mechanism of miR-134 in regulating RGC apoptosis in response to hydrogen peroxide (H2O2) treatment. Results showed that the expression of miR-134 dose- and time-dependently increased in RGC after H2O2 treatment. H2O2-induced RGC apoptosis was significantly attenuated by the inhibition of miR-134 expression by antagomiR-134 and was enhanced by miR-134 overexpression. Luciferase reporter assay revealed a direct interaction between miR-134 and the 3’-untranslated region of cyclic AMP-response element-binding protein (CREB), a critical transcription factor for neuronal protection. In H2O2-treated RGCs, the inhibition of miR-134 significantly elevated the expression of CREB and its downstream genes, including brain-derived neurotrophic factor (BDNF) and Bcl-2. Furthermore, the inhibition of miR-134 also increased the expression of miR-132, a rapid response gene downstream of CREB. In addition, the target gene of miR-132, acetylcholinesterase was expectedly decreased by miR-134 inhibition. However, the overexpression of miR-134 exerted an opposite effect. The knockdown of CREB apparently abolished the protective effect of miR-134 inhibition against H2O2-induced RGC apoptosis. The increased expression of BDNF and Bcl-2 induced by miR-134 inhibition was also abrogated by CREB knockdown. Overall, our results suggested that the downregulation of miR-134 can effectively protect against H2O2-induced RGC apoptosis by negatively modulating CREB expression.

Disturbed spontaneous brain-activity pattern in patients with optic neuritis using amplitude of low-frequency fluctuation: a functional magnetic resonance imaging study

Objective To use the amplitude of low-frequency fluctuation (ALFF) technique to investigate the local features of spontaneous brain activity in optic neuritis (ON) and their relationship with behavioral performance. Materials and methods Twelve patients with ON (four male, eight female) and twelve age-, sex-, and education status-matched healthy controls (HCs) (four male, eight female) underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. The ALFF technique was used to assess local features of spontaneous brain activity. Correlation analysis was used to explore the relationship between the observed mean ALFF values of the different areas and visual evoked potentials (VEPs) in patients with ON. Results Compared with HCs, patients with ON had significantly decreased ALFF values in the posterior and anterior lobes of the right cerebellum, right putamen, right inferior frontal gyrus, right insula, right supramarginal gyrus, right inferior parietal lobule, left medial frontal gyrus, left superior temporal gyrus, bilateral anterior cingulate/medial frontal gyrus, and bilateral precuneus, and significantly increased ALFF values in the posterior lobes of the left and right cerebellum, right inferior temporal gyrus, right inferior temporal/fusiform gyrus, left parahippocampal gyrus, left fusiform gyrus, left calcarine fissure, left inferior parietal lobule, and left cuneus. We found negative correlations between the mean ALFF signal value of the left parahippocampal gyrus and the VEP amplitude of the right eye in ON (r=−0.584, P=0.046), and a positive correlation between the mean ALFF signal value of the bilateral precuneus and the best-corrected visual acuity of the left eye (r=0.579, P=0.048) in patients with ON. Conclusion ON mainly seems to involve dysfunction in the default-mode network, cerebellum, and limbic system, which may reflect the underlying pathologic mechanism of ON.

Therapeutic efficacy of intracameral amphotericin B injection for 60 patients with keratomycosis.

AIM To evaluate the therapeutic efficacy of intracameral amphotericin B (ICAMB) injection in the treatment of keratomycosis. METHODS The study design was a prospective controlled clinical trial. A total of 60 eyes of 60 patients were divided into two groups, 30 in the ICAMB injection group (group A) and 30 in the control group-topical application amphotericin B (group B). Serial measurements of the size of the keratomycosis-namely, two maximum linear dimensions perpendicular to each other, and the area and perimeter was done at start of therapy and follow up on day 3, 7, and 21. Rate of healing of the keratomycosis were measured as percentage decrease from the baseline parameter at each subsequent follow up. The data were analyzed by the non-parametric Wilcoxon rank sum test. RESULTS The mean time to disappearance of hypopyon was 9.6±9.2 (range:1-26) days in group A and 26.8±20.8 (range:14-62) days in group B (P=0.03). The median percentage decrease in the size of the keratomycosis was significantly greater than that in the cord serum group at day 21(P<0.05) when measured in terms of the area and perimeter. A greater number of patients showed complete re-epithelialization in group A (n=27) than in group B (n=14) (P<0.05). None of the patients reported any side effects or discomfort with either treatment. CONCLUSION ICAMB injection leads to faster healing of the keratomycosis refractory to all medical management and reducing time to disapperence of hypopyon compared to topical application amphotericin B.

Synergistic effect of quercetin and 6-gingerol treatment in streptozotocin induced type 2 diabetic rats and poloxamer P-407 induced hyperlipidemia

Ginger and quercetin have been reported to have significant antidiabetic effects. It has been proposed that 6-gingerol and quercetin are responsible for the antidiabetic activity and that a combination of the two produces a synergistic effect. However, the per se effect of 6-gingerol has not been reported. The objective of this study was to investigate the effects of 6-gingerol and quercetin per se, on streptozotocin induced non-insulin dependent diabetes mellitus (NIDDM) and hyperlipidemia. 6-Gingerol and quercetin reduced fasting glucose significantly with producing significant changes in the insulin levels of diabetic rats. The amelioration was significantly more with the combination, compared with either compound alone. The results of the oral glucose tolerance test (OGTT) indicated that 6-gingerol and quercetin reduced streptozotocin (STZ) induced increases in both area under curve glucose (AUCglucose) and area under curve insulin (AUCinsulin) in high fat feed type 2 diabetic rats. Treatment with 6-gingerol and quercetin reduced the levels of lipids in rats with NIDDM significantly. 6-Gingerol and quercetin had antihyperlipidemic effects in polaxamer P-407-induced hyperlipidemia. Quercetin and 6-gingerol show reduced serotonin induced hyperglycemia. This is the first study to demonstrate synergism of 6-gingerol and quercetin that has significant antidiabetic and beneficial cardiac effects in type 2 diabetic rats and polaxamer-induced hyperlipidemic rats. The synergistic action is probably through modulation of the serotonergic system.

altered intrinsic regional spontaneous brain activity in patients with optic neuritis: a resting- state functional magnetic resonance imaging study

Objective To investigate the underlying regional homogeneity (ReHo) in brain-activity deficit in patients with optic neuritis (ON) and its relationship with behavioral performance. Materials and methods In total, twelve patients with ON (four males and eight females) and twelve (four males and eight females) age-, sex-, and education-matched healthy controls underwent resting-state functional magnetic resonance imaging scans. The ReHo method was used to assess the local features of spontaneous brain activity. Correlation analysis was used to explore the relationship between the observed mean ReHo values of the different brain areas and the visual evoked potential (VEP) in patients with ON. Results Compared with the healthy controls, patients with ON showed lower ReHo in the left cerebellum, posterior lobe, left middle temporal gyrus, right insula, right superior temporal gyrus, left middle frontal gyrus, bilateral anterior cingulate cortex, left superior frontal gyrus, right superior frontal gyrus, and right precentral gyrus, and higher ReHo in the cluster of the left fusiform gyrus and right inferior parietal lobule. Meanwhile, we found that the VEP amplitude of the right eye in patients with ON showed a positive correlation with the ReHo signal value of the left cerebellum posterior lobe (r=0.701, P=0.011), the right superior frontal gyrus (r=0.731, P=0.007), and the left fusiform gyrus (r=0.644, P=0.024). We also found that the VEP latency of the right eye in ON showed a positive correlation with the ReHo signal value of the right insula (r=0.595, P=0.041). Conclusion ON may involve dysfunction in the default-mode network, which may reflect the underlying pathologic mechanism.

The expression and distribution of α-Gal gene in various species ocular surface tissue

AIM To examine the α-Gal gene expression and distribution in the different species/genus and developing phase animal ocular surface tissue. METHODS α-Gal binding assay were carried out on various animal eye sections. Photograph, slit-lamp observation on various eye showed normal corneal transparence. RESULTS A strong α-Gal expression in invertebrates and some vertebrates ocular tissue, but no α-Gal binding in birds, fish and mammal. α-Gal expression change in the development of mice ocular surface tissue (except sclera) and display genus dependency in the different murine ocular surface tissue. CONCLUSION This study identified specific α-Gal epitopes binding area in the ocular surface of several species and may solve the problem that naive ocular surface may be used as natural α-Gal gene knockout model/high risk immunologic rejection model or ocular surface scaffold material.

The atrophy of white and gray matter volume in patients with comitant strabismus: Evidence from a voxel-based morphometry study

To compare the difference in white matter volume (WMV) and gray matter volume (GMV) between the comitant strabismus (CS) patients and health controls by voxel-based morphometry (VBM) and the relationship with behavioral performance. A total of 20 patients with comitant strabismus (10 males and 10 females), and 20 healthy subjects (10 males and 10 females) with matched age, sex status underwent magnetic resonance examination. The authors analyzed the original 3D T1 brain images using the VBM module. The comitant strabismus groups were compared with the control groups for the GMW and WMV of the entire brain. Correlation analysis was performed to investigate the relationship between the GMV and WMV altered areas and the behavioral performance in comitant strabismus. CS patients were distinguishable from the healthy controls (HCs) by receiver operating characteristic curves. Results of the VBM analysis demonstrated that the CS groups had decreased GMV in the brain regions of the left middle temporal pole, left cerebellum posterior lobe, right posterior cingulate cortex, left cuneus and right premotor cortex. Meanwhile, the WMV was significantly decreased in the brain regions of the left middle temporal gyrus, right middle temporal gyrus, left middle temporal gyrus, right precuneus and right premotor cortex in the comitant strabismus patients compared with HCs. Furthermore, the duration of CS was negatively correlated with the GMV values of the left middle temporal pole (r=−0.486, P=0.030). CS caused GMV and WMV atrophy in many brain regions, which may indicate the neural mechanisms of the ocular motility disorders in CS patients.