Acanthopanax trifoliatus (L.) Merr polysaccharides ameliorates hyperglycemia by regulating hepatic glycogen metabolism in type 2 diabetic mice.

Introduction: Drug monotherapy was inadequate in controlling blood glucose levels and other comorbidities. An agent that selectively tunes multiple targets was regarded as a new therapeutic strategy for type 2 diabetes. Acanthopanax trifoliatus (L.) Merr polysaccharide (ATMP) is a bio-macromolecule isolated from Acanthopanax trifoliatus (L.) Merr and has therapeutic potential for diabetes management due to its anti-hyperglycemia activity. Methods: Type 2 diabetes mellitus was induced in mice using streptozotocin, and 40 and 80 mg/kg ATMP was administered daily via the intragastric route for 8 weeks. Food intake, water intake, and body weight were recorded. The fasting blood glucose (FBG), fasting insulin (FINS) and an oral glucose tolerance test (OGTT) were performed. Histological changes in the liver and pancreas were analyzed by H&E staining. The mRNA and the protein levels of key factors involved in glycogen synthesis, glycogenolysis, and gluconeogenesis were measured by quantitative real time PCR and Western blotting. Results: In this study, we found that ATMP could effectively improve glucose tolerance and alleviate insulin resistance by promoting insulin secretion and inhibiting glucagon secretion. In addition, ATMP decreases glycogen synthesis by inhibiting PI3K/Akt/GSK3ß signaling, reduces glycogenolysis via suppressing cAMP/PKA signaling, and suppresses liver gluconeogenesis by activating AMPK signaling. Conclusion: Together, ATMP has the potential to be developed as a new multitargets therapeutics for type 2 diabetes.

Time-lapse imaging using dual-color coded quantitative differential phase contrast microscopy.

SIGNIFICANCE: Quantitative differential phase contrast (qDPC) microscopy enhances phase contrast by asymmetric illumination using partially coherent light and multiple intensity measurements. However, for live cell imaging, motion artifacts and image acquisition time are important issues. For live cell imaging, a large number of intensity measurements can limit the imaging quality and speed. The minimum number of intensity measurements in qDPC can greatly enhance performance for live imaging. AIM: To obtain high-contrast, isotropic qDPC images with two intensity measurements and perform time-lapse imaging of biological samples. APPROACH: Based on the color-coded design, a dual-color linear-gradient pupil is proposed to achieve isotropic phase contrast response with two intensity measurements. In our method, the purpose of designing a dual-color coded pupil is twofold: first, to obtain a linear amplitude gradient for asymmetric illumination, which is required to get a circular symmetry of transfer function, and second, to reduce the required number of frames for phase retrieval. RESULTS: To demonstrate the imaging performance of our system, standard microlens arrays were used as samples. We performed time-lapse quantitative phase imaging of rat astrocytes under a low-oxygen environment. Detailed morphology and dynamic changes such as the apoptosis process and migration of cells were observed. CONCLUSIONS: It is shown that dual-color linear-gradient pupils in qDPC can outperform half-circle and vortex pupils, and isotropic phase transfer function can be achieved with only two-axis measurements. The reduced number of frames helps in achieving faster imaging speed as compared to the typical qDPC system. The imaging performance of our system is evaluated by time-lapse imaging of rat astrocytes. Different morphological changes in cells during their life cycle were observed in terms of quantitative phase change values.

Investigation of Possible Correlation Between Retinal Neurovascular Biomarkers and Early Cognitive Impairment in Patients With Chronic Kidney Disease.

Purpose: To investigate the association between retinal neurovascular biomarkers and early cognitive impairment among patients with chronic kidney disease (CKD). Methods: Patients with CKD stage ≥3 were evaluated using the standardized Mini-Mental State Examination (MMSE). Patients were classified as having a low (<24), middle (24 to 27), and high (>27) MMSE level. Retinal nerve fiber layer thickness, ganglion cell complex (GCC) thickness, GCC global loss volume, and GCC focal loss volume were measured using optical coherence tomography (OCT). Superficial vascular plexus vessel density, deep vascular plexus vessel density (DVP-VD), and size of the foveal avascular zone were obtained by OCT angiography. Results: The study enrolled 177 patients with a mean ± SD age of 64.7 ± 6.6 years. The mean ± SD MMSE score was 27.25 ± 2.30. Thirteen, 65, and 99 patients were classified as having a low, middle, and high MMSE level, respectively. The patients with a high MMSE level were younger, had more years of education, had less severe CKD, and had higher DVP-VD than patients with a low MMSE level. The multivariable regression revealed that age (coefficient, 0.294; 95% confidence interval [CI], 0.195-0.393; P = 0.041), years of education (coefficient, 0.294; 95% CI, 0.195-0.393; P < 0.001), estimated glomerular filtration rate (coefficient, 0.019; 95% CI, 0.004-0.035; P = 0.016), and DVP-VD (coefficient, 0.109; 95% CI, 0.007-0.212; P = 0.037) were independent factors associated with MMSE score. Conclusions: Retinal DVP-VD was associated with early cognitive impairment among patients with CKD. Translational Relevance: DVP-VD measured by OCT angiography may facilitate early detection of cognitive impairment.

Multi-wavelength quantitative differential phase contrast imaging by radially asymmetric illumination.

A new approach for achieving isotropic differential phase contrast imaging by applying multi-wavelength asymmetric illumination is demonstrated. Multi-wavelength isotropic differential phase contrast scheme (MW-iDPC) can be implemented using an add-on module in any commercial inverted microscope. Isotropy of intensity transfer function is achieved using three axis measurements. The expression for MW-iDPC imaging is presented, and detailed mathematical analysis is performed for transfer function. By applying color leakage correction, image sensor responses can be calibrated. Asymmetric illumination masks are designed, and simulation studies for intensity of the transfer function are performed. We utilize the MW-iDPC system to reconstruct quantitative phase images of standard microspheres and live breast cancer cells. The optical thickness of cells can be measured with high accuracy and image acquisition time is reduced significantly.

Quantitative differential phase contrast imaging at high resolution with radially asymmetric illumination.

Half-circle illumination-based differential phase contrast (DPC) microscopy has been utilized to recover phase images through a pair of images along multiple axes. Recently, the half-circle based DPC using 12-axis measurements significantly provides a circularly symmetric phase transfer function to improve accuracy for more stable phase recovery. Instead of using half-circle-based DPC, we propose a new scheme of DPC under radially asymmetric illumination to achieve circularly symmetric phase transfer function and enhance the accuracy of phase recovery in a more stable and efficient fashion. We present the design, implementation, and experimental image data demonstrating the ability of our method to obtain quantitative phase images of microspheres, as well as live fibroblast cell samples.

Isotropic differential phase contrast microscopy for quantitative phase bio-imaging.

Quantitative phase imaging (QPI) has been investigated to retrieve optical phase information of an object and applied to biological microscopy and related medical studies. In recent examples, differential phase contrast (DPC) microscopy can recover phase image of thin sample under multi-axis intensity measurements in wide-field scheme. Unlike conventional DPC, based on theoretical approach under partially coherent condition, we propose a new method to achieve isotropic differential phase contrast (iDPC) with high accuracy and stability for phase recovery in simple and high-speed fashion. The iDPC is simply implemented with a partially coherent microscopy and a programmable thin-film transistor (TFT) shield to digitally modulate structured illumination patterns for QPI. In this article, simulation results show consistency of our theoretical approach for iDPC under partial coherence. In addition, we further demonstrate experiments of quantitative phase images of a standard micro-lens array, as well as label-free live human cell samples.

Development of a Microforce Sensor and Its Array Platform for Robotic Cell Microinjection Force Measurement.

Robot-assisted cell microinjection, which is precise and can enable a high throughput, is attracting interest from researchers. Conventional probe-type cell microforce sensors have some real-time injection force measurement limitations, which prevent their integration in a cell microinjection robot. In this paper, a novel supported-beam based cell micro-force sensor with a piezoelectric polyvinylidine fluoride film used as the sensing element is described, which was designed to solve the real-time force-sensing problem during a robotic microinjection manipulation, and theoretical mechanical and electrical models of the sensor function are derived. Furthermore, an array based cell-holding device with a trapezoidal microstructure is micro-fabricated, which serves to improve the force sensing speed and cell manipulation rates. Tests confirmed that the sensor showed good repeatability and a linearity of 1.82%. Finally, robot-assisted zebrafish embryo microinjection experiments were conducted. These results demonstrated the effectiveness of the sensor working with the robotic cell manipulation system. Moreover, the sensing structure, theoretical model, and fabrication method established in this study are not scale dependent. Smaller cells, e.g., mouse oocytes, could also be manipulated with this approach.