An experimental study of VEGF induced changes in vasoactivity in pig retinal arterioles and the influence of an anti-VEGF agent

BACKGROUND: Vascular endothelial growth factor (VEGF) plays an important role in ocular physiology. Anti-VEGF agents are now used for treatment of common retinal diseases. This study characterises the vasoactive properties of VEGF in isolated perfused pig retinal arterioles under normal tone or endothelin-1 (ET-1) pre-contracted conditions and determines the influence of an anti VEGF agent on VEGF induced vasoactivity. METHODS: An isolated perfused retinal arteriole preparation was used. The outer diameter of retinal vessels was monitored at 2 second intervals in response to VEGF and the anti VEGF agent, bevacizumab. The effect of intraluminal delivery of VEGF was determined over a wide concentration range (10(-16) to 10(-7) M) both with and without pre-contraction with ET-1 (3 x 10(-9) M). Bevacizumab (0.35 mg mL(-1)) was applied extraluminally to determine the influence of bevacizumab on VEGF induced vasoactive changes on ET-1 pre-contracted vessels. RESULTS: In retinal arterioles with normal tone, VEGF induced a concentration dependent contraction at low concentrations, reaching 93.5% at 10(-11) M and then contraction was reduced at higher concentrations, recovering to 98.1% at 10(-7) M. VEGF produced a potent concentration dependent vasodilatation in arterioles pre-contracted with ET-1. VEGF induced vasodilatation in arterioles pre-contracted with ET-1 was significantly inhibited by bevacizumab. CONCLUSIONS: VEGF induced vasoactive changes in pig retinal arterioles are dependent on concentration and vascular tone. Bevacizumab inhibits VEGF-induced vasodilatation in pre-contracted arterioles

Redundancy-Free Self-Supervised Relational Learning for Graph Clustering

Graph clustering, which learns the node representations for effective cluster assignments, is a fundamental yet challenging task in data analysis and has received considerable attention accompanied by graph neural networks in recent years. However, most existing methods overlook the inherent relational information among the non-independent and non-identically distributed nodes in a graph. Due to the lack of exploration of relational attributes, the semantic information of the graph-structured data fails to be fully exploited which leads to poor clustering performance. In this paper, we propose a novel self-supervised deep graph clustering method named Relational Redundancy-Free Graph Clustering (R$^2$FGC) to tackle the problem. It extracts the attribute- and structure-level relational information from both global and local views based on an autoencoder and a graph autoencoder. To obtain effective representations of the semantic information, we preserve the consistent relation among augmented nodes, whereas the redundant relation is further reduced for learning discriminative embeddings. In addition, a simple yet valid strategy is utilized to alleviate the over-smoothing issue. Extensive experiments are performed on widely used benchmark datasets to validate the superiority of our R$^2$FGC over state-of-the-art baselines. Our codes are available at https://github.com/yisiyu95/R2FGC.Comment: Accepted by IEEE Transactions on Neural Networks and Learning Systems (TNNLS 2024

Co-expression of apoptin (VP3) and antibacterial peptide cecropin B mutant (ABPS1) genes induce higher rate of apoptosis in HepG2 and A375 cell lines

The antibacterial peptide cecropin B mutant (ABPS1) gene has a broad range of antibacterial and  antiproliferative properties. Apoptin (VP3), a chicken anaemia virus-encoded protein is known to induce  apoptosis in human transformed cells. To explore drug combination in human tumor cells, apoptin and ABPS1 eukaryotic expression vector pIRES2-EGFP-apoptin and pIRES2-EGFP-ABPS1 were constructed and their expression effect individually and in combinations were studied in HepG2 and A375 cells. The vector pIRES2-EGFP-ABPS1 and pIRES2-EGFP-apoptin were transfected into tumor cells HepG2 and A375 by the  lipofectamine-mediated DNA transfection procedure. At 48 h post transfection, the apoptotic rate obtained by flow cytometry and the morphological changes under light and scanning electron microscope of tumor cells  were significant. In contrast, the microvilli on the surface of the control cells were disrupted, decreased and even disappeared. The cell membrane was injured and intracellular substances leaked out. Furthermore, our  results indicate that the apoptotic rates of apoptin (27.32% in HepG2 and 9.34% in A375 cells), were higher  than ABPS1 (23.79% in HepG2 and 8.33% in A375 cells). Moreover, the co-expression of Apoptin and ABPS1  showed higher apoptotic rates which were 27.66 and 10.33% in HepG2 and A375 cells respectively. However, the apoptotic rates obtained in HepG2 cells treated with apoptin and apoptin and ABPS1 together were closely  similar, but, not in A375 cells. Therefore, the results of the present study showed that the combination of  Apoptin and ABPS1 has synergistic effect in HepG2 and A375 cell lines.Keys words: Apoptin, ABPS1, apoptosis, co-expression, HepG2, A375

Laser-Induced Changes in Intraretinal Oxygen Distribution in Pigmented Rabbits

PURPOSE. To make the first measurements of intraretinal oxygen distribution and consumption after laser photocoagulation of the retina and to compare the efficiency of micropulsed (MP) and continuous wave (CW) laser delivery in achieving an oxygen benefit in the treated area. METHODS. Oxygen-sensitive microelectrodes were used to measure oxygen tension as a function of retinal depth before and after laser treatment in anesthetized, mechanically ventilated, Dutch Belted rabbits (n ϭ 11). Laser lesions were created by using a range of power levels from an 810-nm diode laser coupled with an operating microscope delivery system. MP duty cycles of 5%, 10%, and 15% were compared with CW delivery in each eye. RESULTS. Sufficient power levels of both the CW and MP laser reduced outer retinal oxygen consumption and increased oxygen level within the retina. At these power levels, which correlated with funduscopically visible lesions, there was histologically visible damage to the RPE and photoreceptors. Retinal damage was energy dependent but short-duty-cycle MP delivery was more selective in terms of retinal cell damage, with a wider safety range in comparison with CW delivery. CONCLUSIONS. The relationship between laser power level and mode of delivery and the resultant changes in oxygen metabolism and oxygen level in the retina was determined. Only partial destruction of RPE and photoreceptors is necessary, to produce a measurable oxygen benefit in the treated area of retina. (Invest Ophthalmol Vis Sci. 2005;46:988 -999

Label-Free Density Measurements of Radial Peripapillary Capillaries in the Human Retina

Radial peripapillary capillaries (RPCs) comprise a unique network of capillary beds within the retinal nerve fibre layer (RNFL) and play a critical role in satisfying the nutritional requirements of retinal ganglion cell (RGC) axons. Understanding the topographical and morphological characteristics of these networks through in vivo techniques may improve our understanding about the role of RPCs in RGC axonal health and disease. This study utilizes a novel, non-invasive and label-free optical imaging technique, speckle variance optical coherence tomography (svOCT), for quantitatively studying RPC networks in the human retina. Six different retinal eccentricities from 16 healthy eyes were imaged using svOCT. The same eccentricities were histologically imaged in 9 healthy donor eyes with a confocal scanning laser microscope. Donor eyes were subject to perfusion-based labeling techniques prior to retinal dissection, flat mounting and visualization with the microscope. Capillary density and diameter measurements from each eccentricity in svOCT and histological images were compared. Data from svOCT images were also analysed to determine if there was a correlation between RNFL thickness and RPC density. The results are as follows: (1) The morphological characteristics of RPC networks on svOCT images are comparable to histological images; (2) With the exception of the nasal peripapillary region, there were no significant differences in RPC density measurements between svOCT and histological images; (3) Capillary diameter measurements were significantly greater in svOCT images compared to histology; (4) There is a positive correlation between RPC density and RNFL thickness. The findings in this study suggest that svOCT is a reliable modality for analyzing RPC networks in the human retina. It may therefore be a valuable tool for aiding our understanding about vasculogenic mechanisms that are involved in RGC axonopathies. Further work is required to explore the reason for some of the quantitative differences between svOCT and histology

The Effect of Surfactants on the Diameter and Morphology of Electrospun Ultrafine Nanofiber

Different surfactants are introduced to study the diameter and morphology transformation characteristics of electrospun nanofiber. Surfactants increase the net charge density and instability motion of charged jet. The instability motion provides a good way to stretch the charged jets into finer ones, by which the beaded structures are also prevented. Ultrafine nanofiber with average diameter less than 65 nm can be fabricated. The nanofiber diameter decreases with the increase of surfactant concentration in polymer solution. The nanofibers with anionic surfactant sodium dodecyl sulfate (SDS) have the smallest diameter. The cationic surfactant hexadecyl trimethyl ammonium bromide (HTAB) plays the best role to prevent the formation of beaded structures in nanofibers, and helps to increase the uniformity of electrospun nanofiber. The effects of surfactants on the nanofiber diameter and morphology have been studied, which would promote the industrial application of ultrafine polymeric nanofibers

TECHNICAL NOTE - Isolation of simple sequence repeats from groundnut

SSRs have proved to be the most powerful tool for variety identification in groundnut of similar origin, and have much potential in genetic and breeding studies. To facilitate SSR discovery in groundnut, we proposed a highly simplified SSR isolation protocol based on multiple enzyme digestion/ligation, mixed biotin-labeled probes and streptavidin coated magnetic beads hybridization capture strategy. Of the 272 colonies randomly picked for sequencing, 119 were found to have unique SSR inserts

Low-cost wearable sensor based on a D-shaped plastic optical fiber for respiration monitoring

A low cost, wearable textile-based respiratory sensing system is proposed and experimentally demonstrated. A highly sensitive D-shaped plastic optical fiber (POF) sensor that responds to bending is integrated into an elastic band structure to form a respiratory sensing system. The curvature sensing experiments were conducted on the D-shaped POF sensor, which has a coefficient of determination (R2) of 0.9977. The system can be used to monitor not only the respiratory rate (RR) of the human body under different movement states (resting, walking and running), but also the RR of steady and unsteady respiratory signals due to different physiological states. In addition, using the proposed signal processing technique, the interference of motion noise can be removed and the influence of body movement on the sensor response can be eliminated. The advantages of the system are its low cost, compactness and simplicity in design. Thus, the application of the proposed respiratory sensing system provides a simple and inexpensive optical solution for wearable health

Detecting Key Functional Components Group and Speculating the Potential Mechanism of Xiao-Xu-Ming Decoction in Treating Stroke

Stroke is a cerebrovascular event with cerebral blood flow interruption which is caused by occlusion or bursting of cerebral vessels. At present, the main methods in treating stroke are surgical treatment, statins, and recombinant tissue-type plasminogen activator (rt-PA). Relatively, traditional Chinese medicine (TCM) has widely been used at clinical level in China and some countries in Asia. Xiao-Xu-Ming decoction (XXMD) is a classical and widely used prescription in treating stroke in China. However, the material basis of effect and the action principle of XXMD are still not clear. To solve this issue, we designed a new system pharmacology strategy that combined targets of XXMD and the pathogenetic genes of stroke to construct a functional response space (FRS). The effective proteins from this space were determined by using a novel node importance calculation method, and then the key functional components group (KFCG) that could mediate the effective proteins was selected based on the dynamic programming strategy. The results showed that enriched pathways of effective proteins selected from FRS could cover 99.10% of enriched pathways of reference targets, which were defined by overlapping of component targets and pathogenetic genes. Targets of optimized KFCG with 56 components can be enriched into 166 pathways that covered 80.43% of 138 pathways of 1,012 pathogenetic genes. A component potential effect score (PES) calculation model was constructed to calculate the comprehensive effective score of components in the components-targets-pathways (C-T-P) network of KFCGs, and showed that ferulic acid, zingerone, and vanillic acid had the highest PESs. Prediction and docking simulations show that these components can affect stroke synergistically through genes such as MEK, NFκB, and PI3K in PI3K-Akt, cAMP, and MAPK cascade signals. Finally, ferulic acid, zingerone, and vanillic acid were tested to be protective for PC12 cells and HT22 cells in increasing cell viabilities after oxygen and glucose deprivation (OGD). Our proposed strategy could improve the accuracy on decoding KFCGs of XXMD and provide a methodologic reference for the optimization, mechanism analysis, and secondary development of the formula in TCM