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Vitreous, a transparent tissue in our body, contains anti-angiogenesis factors. Our previous work reported that vitreous activates the signaling pathway of epidermal growth factor receptor (EGFR), which plays a critical role in angiogenesis. The aim of this study was to determine the role of EGFR in vitreous-induced angiogenesis-related cellular responses in vitro. Using a pharmacologic and molecular approach, we found that vitreous increased proliferation and migration via EGFR in human umbilical vein endothelial cells (HUVECs). Furthermore, we demonstrated that vitreous promoted tube formation via EGFR in HUVECs. Subsequently, depletion of EGFR using CRISPR/Cas9 and blockage with EGFR inhibitor AG1478 suppressed vitreous-induced Akt activation and cell proliferation, migration, and tube formation in HUVECs. The significance of the angiogenic effect derived from vitreous demonstrates the importance of vitreous in the ocular physiology and the pathobiology of angiogenesis-related ophthalmic diseases, such as proliferative diabetic retinopathy.

Fish bile has long been considered to have therapeutic benefits in folk medicine in some Asian countries. However, poisoning incidents and even death sporadically occurred when people consumed fish bile. Herein, we summarize the main characteristics of fish bile poisoning in China including clinical symptoms, treatment strategies and factors being associated with death and affecting prognosis, hoping to provide a reference for the diagnosis and treatment of fish bile poisoning, as well as forensic identification of death cases induced by fish bile poisoning. We suggest that the health authorities should make an effort to enhance people's awareness of the safety of traditional medicine like fish bile so as to reduce the incidence of adverse events.

Receptor‐interacting protein 3 (RIP3) plays an important role in the necroptosis signaling pathway. Our previous studies have shown that the RIP3/mixed lineage kinase domain‐like protein (MLKL)‐mediated necroptosis occurs in retinal ganglion cell line 5 (RGC‐5) following oxygen‐glucose deprivation (OGD). However, upstream regulatory pathways of RIP3 are yet to be uncovered. The purpose of the present study was to investigate the role of p90 ribosomal protein S6 kinase 3 (RSK3) in the phosphorylation of RIP3 in RGC‐5 cell necroptosis following OGD. Our results showed that expression of RSK3, RIP3, and MLKL was upregulated in necroptosis of RGC‐5 after OGD. A computer simulation based on our preliminary results indicated that RSK3 might interact with RIP3, which was subsequently confirmed by co‐immunoprecipitation. Further, we found that the application of a specific RSK inhibitor, LJH685, or rsk3 small interfering RNA (siRNA), downregulated the phosphorylation of RIP3. However, the overexpression of rip3 did not affect the expression of RSK3, thereby indicating that RSK3 could be a possible upstream regulator of RIP3 phosphorylation in OGD‐induced necroptosis of RGC‐5 cells. Moreover, our in vivo results showed that pretreatment with LJH685 before acute high intraocular pressure episodes could reduce the necroptosis of retinal neurons and improve recovery of impaired visual function. Taken together, our findings suggested that RSK3 might work as an upstream regulator of RIP3 phosphorylation during RGC‐5 necroptosis.

PURPOSE To evaluate iris volume before and after pupil dilation using swept-source anterior segment optical coherence tomography (SS-ASOCT) and investigate the associated factors of iris volume and iris volume change after pupil dilation in patients with type 2 diabetes mellitus (T2DM). METHODS A cross-sectional study was conducted in Zhongshan Ophthalmic Center among T2DM registered patients in the community of Guangzhou, China. Anterior chamber volume (ACV), iris volume, anterior chamber depth (ACD), angle opening distance at 500 μm (AOD 500) and pupil diameter were estimated using SS-ASOCT (CASIA; Tomey, Nagoya, Japan). Venous blood was taken for the measurement of glycosylated haemoglobin A1c (HbAlc). All biometric measurements were performed before and after pharmacologic pupil dilation. RESULTS A total of 117 subjects were included in the analysis. The mean age (±SD) was 64.96 ± 7.75 years, and 62.4% were females. After pupil dilation, iris volume decreased in all eyes. Shorter duration of diabetes (p = 0.035), longer axial length (p

Given the importance of non-coding RNAs in modulating normal brain functions and their implications in the treatment of neurological disorders, non-coding RNA-based diagnostic and therapeutic strategies have shown great clinical potential. Circular RNAs (circRNAs) have emerged as potentially important players in this field. Recent studies have indicated that circRNAs might play vital roles in Alzheimer's disease, Parkinson's disease, ischemic brain injury, and neurotoxicity. However, the mechanisms of action of circRNAs have not been fully characterized. We aimed to review recent advances in circRNA research in the brain to provide new insights on the roles of circRNAs in neurological disorders.

Background Long noncoding RNAs (lncRNAs) play crucial roles in fibrosis process. In our previous RNA-seq study, we found that lncRNA myocardial infarction-associated transcript (MIAT) was differentially expressed in pancreatic tissues of chronic pancreatitis (CP) patients. However, the function of MIAT in CP remains unknown. This study was aimed to investigate the function and underlying mechanism of MIAT in pancreatic fibrosis. Materials and methods The expression levels of MIAT, miR-216a-3p, cyclooxygenase 2 (COX-2), α-smooth muscle actin (α-SMA), and collagen I were estimated by Western blot analysis and qualitative reverse transcription polymerase chain reaction. The relationships between miR-216a-3p, MIAT, and COX-2 were confirmed by luciferase reporter assay. The proliferation of human pancreatic stellate cells (HPaSteCs) was detected by cell counting kit-8 assay. Results We found that MIAT, along with the levels of fibrosis-related proteins α-SMA and collagen I, as well as COX-2 were upregulated, while miR-216a-3p was downregulated in transforming growth factor (TGF)-β1-stimulated HPaSteCs. Mechanistically, MIAT acted as a molecular sponge for miR-216a-3p. Furthermore, we identified COX-2 as a direct target of miR-126a-3p. Additionally, MIAT overturned the inhibitory effect of miR-216a-3p overexpression and COX-2 knockdown on the activation and proliferation of HPaSteCs. Conclusion Our study provided mechanistic insights into a critical role for MIAT as a miRNA sponge in CP.

Both in mainland China and around the world, regional anatomy stands as one of the most important basic science courses in medical school curricula. As such, dissection of human cadavers and use of prosected specimens remains the most essential teaching method in anatomy education. However, medical educators have raised increasing concerns about an ongoing shortage of cadavers for medical use in mainland China, a problem which may seriously limit the future development of human anatomy education. Based on a survey on cadaver usage in anatomy education in mainland China, this study found that the cadaver resources of most given medical schools in mainland China are associated with their geographic location, academic ranking, and local support for body donation policies. Effective measures to alleviate this shortage of cadavers may include future efforts to promote national-level body donation legislation, broader acceptance of body donation among Chinese citizens, and an efficient and humane protocol for body donation. Anat Sci Educ 11: 397-402. © 2018 American Association of Anatomists.

Mesoporous M-CeO2 (M = Ni, Co, Fe, Mn, and Cu) catalysts were prepared using the hard-template method and applied to investigate CO2 reverse water-gas shift (RWGS) reaction. The physicochemical properties were studied using H2-TPR, XRD, BET, CO2-TPD, and H2-TPD. Results show that the specific surface areas of the prepared Ni-CeO2, Co-CeO2, Fe-CeO2, Mn-CeO2, and Cu-CeO2 catalysts exceed 120 m2/g. CO2 RWGS reaction performances are affected by the d-orbital holes of transition metals. CO2 RWGS reaction catalytic activities are ranked as follows: Ni-CeO2 > Cu-CeO2 > Co-CeO2 > Fe-CeO2 ≈ Mn-CeO2. The Cu-CeO2, Fe-CeO2, and Mn-CeO2 catalysts maintain 100% CO selectivity at the studied temperature. This article is protected by copyright. All rights reserved

The global epidemic features of enteric fever have changed greatly in recent years. The incidence of enteric fever caused by Salmonella enterica serovar Paratyphi A has progressively increased. In some areas of Asia, infections with S. Paratyphi A have exceeded those with S. Typhi, resulting in S. Paratyphi A becoming the main causative agent of enteric fever. However, two currently licensed typhoid vaccines do not confer adequate cross-protection against S. Paratyphi A infection. Therefore, development of specific vaccines against enteric fever caused by S. Paratyphi A is urgently needed. In the present study, an attenuated strain was constructed by double deletion of the htrA and yncD genes in a wild-type strain of S. Paratyphi A and its safety and immunogenicity assessed. In a mouse model, the 50% lethal dose of the double deletion mutant and the wild-type strain were 3.0 × 108 CFU and 1.9 × 103 CFU, respectively, suggesting that the double deletion resulted in remarkably decreased bacterial virulence. Bacterial colonization of the double deletion mutant in the livers and spleens of infected mice was strikingly less than that of the wild-type strain. A single nasal administration of the attenuated vaccine candidate elicited high concentrations of anti-LPS and anti-flagellin IgG in a mouse model and protected immunized mice against lethal challenge with the wild-type strain. Thus, our findings suggest that the attenuated vaccine strain is a promising candidate worthy of further evaluation both as a human enteric fever vaccine and as a vaccine delivery vector for heterologous antigens.

Owing to their good osseointegration property, calcium silicate (CS) bioceramics have been extensively studied in recent years. Nevertheless, the excessively high environmental pH value of CS bioceramics will limit their clinical application. The purpose of this work is to reduce the dissolution of Ca and Si ions from the pure CS bioceramics by modifying its surface structure and chemical composition with Zn2SiO4 nanoparticles (Zn–CS bioceramic). The results indicated that the dissolution of Ca and Si ions from the CS substrate obviously decreased by the surface modification, and the pH value of the soaking liquid was also effectively controlled. SEM observation and EDS analysis showed that apatite mainly formed on the wall of the internal pores under the Zn-containing porous surface layer when the Zn–CS bioceramic was soaked in the simulated body fluids (SBF). Moreover, cell adhesion assay proved that mouse osteoblast cells (MC3T3) well adhered and spread on the Zn-containing porous surface layer, and the apatite formed on the surface of the Zn-containing porous layer during the incubation process. Better bioactivity and the osseointegration property can be expected for Zn–CS bioceramic. The surface modification with Zn2SiO4 nanoparticles is a promising route to control the dissolution and environmental pH value of CS bioceramics.

As an important trace element in human bone, zinc (Zn) has a great influence on bone metabolism. The aim of this work was to prepare a Zn-containing material that can release Zn ions. For this purpose, submicrometer willemite phase zinc silicate (Zn2SiO4, ZS) with poor crystallinity was synthesized at 110°C via the microwave-assisted hydrothermal (MH) method. Under the MH condition, the growth of ZS was consistent with “multi-core growth” mechanism. Moreover, the influences of the reaction temperature and the reactant concentration on the final products were investigated in detail. The inductively coupled plasma atomic emission spectroscopy (ICP) data indicated that the poor crystallinity ZS could successfully release Zn for at least 28 d as soaking in the simulated body fluid (SBF). Without the replenishment of SBF, ~333 μM Zn was released from ZS synthesized at 110°C (ZS-110). If SBF was periodically replenished once a day, more Zn was released from ZS-110, and the parascholzite phase calcium zinc phosphate hydrate (CaZn2(PO4)2·2H2O) formed during the soaking process of ZS-110. Under the concentration of 6.25 mg/mL, the extract of ZS-110 was proved to be nontoxic by assessing with mouse osteoblast cells (MC3T3). Therefore, the poor crystallinity ZS has potential to be incorporated into the orthopedic reconstructive materials as a source of Zn ions, which can improve the bioactivity of the materials.

Alzheimer's disease (AD) is the most common dementia-causing disorder in the elderly; it may be related to multiple risk factors, and is characterized pathologically by cerebral hypometabolism, paravascular β-amyloid peptide (Aβ) plaques, neuritic dystrophy, and intra-neuronal aggregation of phosphorylated tau. To explore potential pathogenic links among some of these lesions, we examined β-secretase-1 (BACE1) alterations relative to Aβ deposition, neuritic pathology and vascular organization in aged monkey and AD human cerebral cortex. Western blot analyses detected increased levels of BACE1 protein and β-site-cleavage amyloid precursor protein C-terminal fragments in plaque-bearing human and monkey cortex relative to controls. In immunohistochemistry, locally elevated BACE1 immunoreactivity (IR) occurred in AD but not in control human cortex, with a trend for increased overall density among cases with greater plaque pathology. In double-labeling preparations, BACE1 IR colocalized with immunolabeling for Aβ but not for phosphorylated tau. In perfusion-fixed monkey cortex, locally increased BACE1 IR co-existed with intra-axonal and extracellular Aβ IR among virtually all neuritic plaques, ranging from primitive to typical cored forms. This BACE1 labeling localized to swollen/sprouting axon terminals that might co-express one or another neuronal phenotype markers (GABAergic, glutamatergic, cholinergic, or catecholaminergic). Importantly, these BACE1-labeled dystrophic axons resided near to or in direct contact with blood vessels. These findings suggest that plaque formation in AD or normal aged primates relates to a multisystem axonal pathogenesis that occurs in partnership with a potential vascular or metabolic deficit. The data provide a mechanistic explanation for why senile plaques are present preferentially near the cerebral vasculature.

An on-column preconcentration technique, pH-mediated acid stacking, was used in this study to improve the sensitivity of MEKC-UV analysis of IgG in human serum. Various parameters affecting pH-mediated acid stacking were optimized systematically. To eliminate the matrix interferences of human serum and to combine the sample pretreatment procedure with the detection methodology, silica-coated Fe 3 O 4 magnetic nanoparticles modified with N-(2-aminoethyl)-3-aminopropyl-trimethoxysilane were prepared and employed as solid phase extraction adsorbent to remove the abundant HSA from human serum. HSA was quantitatively removed by silica-coated Fe 3 O 4 magnetic nanoparticles modified with N-(2-aminoethyl)-3-aminopropyl-trimethoxysilanes without retaining IgG at pH 9.3. Under the optimum conditions, the sensitivity of IgG was improved 40.3-fold using a 100 s electrokinetic injection as compared with a 6 s hydrodynamic injection. The detection limit of IgG was found to be 0.1 mg/L, and the proposed method was successfully applied for the determination of IgG in human serum with satisfactory results.

Cerebral hypometabolism and amyloid accumulation are principal neuropathological manifestations of Alzheimer's disease (AD). Whether and how brain/neuronal activity might modulate certain pathological processes of AD are interesting topics of recent clinical and basic research in the field, and may be of potential medical relevance in regard to both the disease etiology and intervention. Using the Tg2576 transgenic mouse model of AD, this study characterized a promotive effect of neuronal hypoactivity associated with functional deprivation on amyloid plaque pathogenesis in the olfactory pathway. Unilateral naris-occlusion caused beta-secretase-1 (BACE1) elevation in neuronal terminals in the deprived relative to the non-deprived bulb and piriform cortex in young adult mice. In parallel with the overall age-related plaque development in the forebrain, locally increased BACE1 immunoreactivity co-occurred with amyloid deposition first in the piriform cortex then within the bulb, more prominent on the deprived relative to the non-deprived side. Biochemical analyses confirmed elevated BACE1 protein levels, enzymatic activity and products in the deprived relative to non-deprived bulbs. Plaque-associated BACE1 immunoreactivity in the bulb and piriform cortex was localized preferentially to swollen/sprouting glutamatergic axonal terminals, with Abeta immunoreactivity occurring inside as well as around these terminals. Together, these findings suggest that functional deprivation or neuronal hypoactivity facilitates amyloid plaque formation in the forebrain in a transgenic model of AD, which operates synergistically with age effect. The data also implicate an intrinsic association of amyloid accumulation and plaque formation with progressive axonal pathology.

The presence of neuritic plaques is a pathological hallmark of Alzheimer's disease (AD). However, the origin of extracellular beta-amyloid peptide (Abeta) deposits and the process of plaque development remain poorly understood. The present study attempted to explore plaque pathogenesis by localizing beta-secretase-1 (BACE1) elevation relative to Abeta accumulation and synaptic/neuritic alterations in the forebrain, using transgenic mice harboring familial AD (FAD) mutations (5XFAD and 2XFAD) as models. In animals with fully developed plaque pathology, locally elevated BACE1 immunoreactivity (IR) coexisted with compact-like Abeta deposition, with BACE1 IR occurring selectively in dystrophic axons of various neuronal phenotypes or origins (GABAergic, glutamatergic, cholinergic or catecholaminergic). Prior to plaque onset, localized BACE1/Abeta IR occurred at swollen presynaptic terminals and fine axonal processes. These BACE1/Abeta-containing axonal elements appeared to undergo a continuing process of sprouting/swelling and dystrophy, during which extracellular Abeta IR emerged and accumulated in surrounding extracellular space. These data suggest that BACE1 elevation and associated Abeta overproduction inside the sprouting/dystrophic axonal terminals coincide with the onset and accumulation of extracellular amyloid deposition during the development of neuritic plaques in transgenic models of AD. Our findings appear to be in harmony with an early hypothesis that axonal pathogenesis plays a key or leading role in plaque formation.

A method has been developed for the separation and determination of three hydrophobic benzophenones: 2,4-dihydroxybenzophenone (BP-1), 2,2'4,4'-tetrahydroxybenzophenone (BP-2), and 2-hydroxy-4-methoxybenzophenone (BP-3) in sunscreen by micellar electrokinetic capillary chromatography (MEKC) combined with cloud point extraction (CPE). The analytes were extracted at pH 5.0 by micelles of the nonionic surfactant polyoxyethylene-7.5-octylphenyl ether (Triton X-114). A 150 microL aliquot from the extracted surfactant-rich phase was diluted up to 500 microL with ethanol to reduce its viscosity before separation by MEKC. A background electrolyte of 25 mmol/L sodium tetraborate containing 30 mmol/L sodium dodecyl sulfate at pH 9.25 was used as the separation medium to avoid the adsorption of hydrophobic substances and Triton X-114 onto the inner surface of the separation capillary, ensuring the separation efficiency and reproducibility. Detection is performed at 290 nm. Under the optimized conditions, an enrichment factor of 20 was obtained and the determination limits of BP-1, BP-2, and BP-3 were found to be 3.90 x 10(-) (7), 3.83 x 10(-7), and 6.42 x 10(-8) mol/L, respectively. In comparison with the earlier reported methods, the LODs of this method are superior to the other methods. The presented procedure was successfully applied to the determination of BP-1, BP-2, and BP-3 in sunscreen with satisfactory results.

Hinokiflavone has drawn a lot of attention for its multiple biological activities. In this study, a sensitive and selective method for determination of hinokiflavone in rat plasma was developed for the first time, using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Amentoflavone was used as an internal standard. Separation was achieved on a Hypersil Gold C18 column with isocratic elution using methanol-water (65:35, v/v) as mobile phase at a flow rate of 0.3 mL/min. A triple quadrupole mass spectrometer operating in the negative electrospray mode with selected reaction monitoring (SRM) was used to detect the transitions of m/z 537 → 284 for hinokiflavone and m/z 537 → 375 for IS. The LOQ was 0.9 ng/mL with a linear range of 0.9–1000 ng/mL. The intra- and inter-day accuracy (RE%) ranged from –3.75 to 6.91% and –9.20 to 2.51% and the intra- and inter-day precision (RSD%) was between 0.32–14.11% and 2.85–10.04%. The validated assay was successfully applied to a pharmacokinetic study of hinokiflavone in rats. The half-life of drug elimination (t1/2) at the terminal phase was 6.10 ± 1.86 h, and the area under the plasma concentration-time curve from time zero to the time of last measurable concentration (AUC0–t) and to infinity (AUC0–∞) values obtained were 2394.42 ± 466.86 and 2541.93 ± 529.85 h ng/mL, respectively.