Adipose-derived stem cells can alleviate RHDV2 induced acute liver injury in rabbits.

Rabbit hemorrhagic disease virus (RHDV) can cause fatal fulminant hepatitis, which is very similar to human acute liver failure. The aim of this study was to investigate whether adipose-derived stem cells (ADSCs) could alleviate RHDV2-induced liver injury in rabbits. Twenty 50-day-old rabbits were divided randomly into two groups (RHDV2 group, ADSCs + RHDV2 group). Starting from the 1st day, two groups of rabbits were given 0.5 ml of viral suspensions by subcutaneous injection in the neck. Meanwhile, the ADSCs + RHDV2 group was injected with ADSCs cell suspension (1.5 × 107 cells/ml) via a marginal ear vein, and the RHDV2 group was injected with an equal amount of saline via a marginal ear vein. At the end of the 48 h experiment, the animals were euthanized and gross hepatic changes were observed before liver specimens were collected. Histopathological analysis was performed using hematoxylin-eosin (HE), periodic acid schiff (PAS) and Masson's trichrome staining. For RHDV2 affected rabbits, HE staining demonstrated disorganized hepatic cords, loss of cellular detail, and severe cytoplasmic vacuolation within hepatocytes. Glycogen was not observed with PAS staining, and Masson's Trichrome staining showed increased hepatic collagen deposition. For rabbits treated with ADSCs at the time of inoculation, hepatic pathological changes were significantly less severe, liver glycogen synthesis was increased, and collagen fiber deposition was decreased. For RHDV2 affected rabbits, Tunel and immunofluorescence staining showed that the number of apoptotic cells, TGF-ß, and MMP-9 protein expression increased. And that in the ADSC treated group there was less hepatocyte apoptosis. In addition, RHDV2 induces liver inflammation and promotes the expression of IL-1ß, IL-6, and TNF-α. In rabbits administered ADSCs at time of inoculation, the expression of inflammatory factors in liver tissue decreased significantly. Our experiments show that ADSCs can protect rabbits from liver injury by RHDV2 and reduce the pathological and inflammatory response of liver. However, the specific protective mechanism needs further study.

Effects of adipose derived stem cells pretreated with resveratrol on sciatic nerve regeneration in rats.

Adipose derived stem cells (ADSCs) are popular in regenerative medicine due to their easy availability, low immunogenicity and lack of controversy regarding their ethical debate use. Although ADSCs can repair nerve damage, the oxidative microenvironment of damaged tissue can induce apoptosis of transplanted stem cells, which weakens the therapeutic efficacy of ADSCs. Resveratrol (Res) is a type of natural polyphenol compound that regulates the proliferation, senescence and differentiation of stem cells. Therefore, we investigated whether incubation of ADSCs with Res improves their to promote peripheral nerve regeneration. ADSCs were cultured in vitro and treated with H2O2 to establish an apoptosis model. The control, H2O2 and Res groups were set up. The cell survival rate was detected by the CCK-8 method. The TUNEL assay was used to detect the apoptosis of the cells. qRT‒PCR was used to analyze the expression of apoptosis-related mRNA, and the effect of Res on the proliferation of ADSCs was investigated. In vivo, 40 SD rats were randomly divided into the control, model, ADSCs and ADSC + Res groups, with 13 rats in each group. The sciatic nerve injury rat model was established by the clamp method. Gait was observed on Days 7, 14, 21, and 28. Sciatic nerve regeneration was detected on Day 28. Res had no effect on the proliferation of ADSCs, and the TUNEL assay confirmed that Res pretreatment could significantly improve H2O2-induced apoptosis in ADSCs. Compared with the control group, caspase-3, Bax and Bcl-2 expression levels were significantly increased in the H2O2 group. Compared with the H2O2 group caspase-3 and Bax expression levels were significantly decreased, and Bcl-2 expression levels were significantly increased in ADSCs + Res group. At 4 weeks after surgery, the functional index of the sciatic nerve in the ADSCs + Res group was significantly higher than that in the model group. On Day 28, the average density of the sciatic nerve myelin sheath in the ADSCs + Res group was significantly increased compared with that in the model group, and Nissl staining showed that the number of motor neurons in the spinal cord was significant compared with that in the model group. Compared with the control group, the wet weight ratio of gastrocnemius muscle and muscle fiber area in ADSCs + Res group were significantly increased. Res enhanced the ability of ADSCs to promote sciatic nerve regeneration in rats.

ADSCs Combined with Melatonin Promote Peripheral Nerve Regeneration through Autophagy.

Background: In the early stage of nerve injury, damaged tissue is cleared by autophagy. ADSCs can promote nerve axon regeneration. However, the microenvironment of the injury was changed, and ADSCs are easily apoptotic after transplantation. Mel plays a role in the apoptosis, proliferation, and differentiation of ADSCs. Therefore, we investigated whether Mel combined with ADSCs promoted peripheral nerve regeneration by enhancing early autophagy of injured nerves. Materials and Methods: SD rats were randomly split into the control group, model group, Mel group, ADSCs group, ADSCs + Mel group, and 3-MA group. On day 7, autophagy was observed and gait was detected on days 7, 14, 21, and 28. On the 28th day, the sciatic nerve of rats' renewal was detected. Results: After 1 w, compare with the model group, the number of autophagosomes and lysosomes and the expressions of protein of LC3-II/LC3-I and Beclin-1 in the ADSCs + Mel group were prominently increased, while the 3-MA group was significantly decreased. After 4 w, the function of the sciatic nerve in ADSCs + Mel was similar to that in the control group. Compared with the model group, the ADSCs + Mel group significantly increased myelin regeneration and the number of motor neurons and reduced gastrocnemius atrophy. Conclusions: It was confirmed that ADSCs combined with Mel could promote sciatic nerve regeneration in rats by changing the early autophagy activity of the injured sciatic nerve.

Effect of dialyzer membranes on mortality in uremic patients undergoing long-term hemodialysis: A Nationwide population-based study using the Taiwan Dialysis Registry Data System 2005-2012.

The characteristics in dialyzer are associated with mortality in patients with end-stage renal disease (ESRD) receiving hemodialysis (HD). This study is to investigate the effects of dialyzer membranes on 3-year mortality in ESRD patients. From the long-term nationwide population database. Prevalent HD patients during 2005-2012 were enrolled. Our main analysis to calculate the effect was cox regression multivariate model. Overall, the mean age of all population (N = 73 565) was 61.0 ± 13.6 years, the observation period is 2.46 years ±0.98 within 3 years and 64.6% used polysulfone (PS), polymethyl methacrylate (PMMA) (11.6%), polyethersulfone (11.4%), and cellulose triacetate (CTA) (10.7%), ethylene vinyl alcohol (EVAL) (hazard ratio [HR] 2.72, 95% confidence interval [CI] 1.71-4.33) and CTA (HR 1.35, 95% CI 1.12-1.64) were associated with higher mortality than PS, but PMMA was not. EVAL and CTA adversely affected mortality and PMMA had no protective role. Further investigations on membrane characters on HD patients are warranted. Taipei Medical University (TMU) (TMU-JIRB (No. N201804051).

Closed-Loop Torque and Kinematic Control of a Hybrid Lower-Limb Exoskeleton for Treadmill Walking.

Restoring and improving the ability to walk is a top priority for individuals with movement impairments due to neurological injuries. Powered exoskeletons coupled with functional electrical stimulation (FES), called hybrid exoskeletons, exploit the benefits of activating muscles and robotic assistance for locomotion. In this paper, a cable-driven lower-limb exoskeleton is integrated with FES for treadmill walking at a constant speed. A nonlinear robust controller is used to activate the quadriceps and hamstrings muscle groups via FES to achieve kinematic tracking about the knee joint. Moreover, electric motors adjust the knee joint stiffness throughout the gait cycle using an integral torque feedback controller. For the hip joint, a robust sliding-mode controller is developed to achieve kinematic tracking using electric motors. The human-exoskeleton dynamic model is derived using Lagrangian dynamics and incorporates phase-dependent switching to capture the effects of transitioning from the stance to the swing phase, and vice versa. Moreover, low-level control input switching is used to activate individual muscles and motors to achieve flexion and extension about the hip and knee joints. A Lyapunov-based stability analysis is developed to ensure exponential tracking of the kinematic and torque closed-loop error systems, while guaranteeing that the control input signals remain bounded. The developed controllers were tested in real-time walking experiments on a treadmill in three able-bodied individuals at two gait speeds. The experimental results demonstrate the feasibility of coupling a cable-driven exoskeleton with FES for treadmill walking using a switching-based control strategy and exploiting both kinematic and force feedback.

Digital holographic microtomography for high-resolution refractive index mapping of live cells.

Quantification of three-dimensional (3D) refractive index (RI) with sub-cellular resolution is achieved by digital holographic microtomography (DHµT) using quantitative phase images measured at multiple illumination angles. The DHµT system achieves sensitive and fast phase measurements based on iterative phase extraction algorithm and asynchronous phase shifting interferometry without any phase monitoring or active control mechanism. A reconstruction algorithm, optical diffraction tomography with projection on convex sets and total variation minimization, is implemented to substantially reduce the number of angular scattered fields needed for reconstruction without sacrificing the accuracy and quality of the reconstructed 3D RI distribution. Tomogram of a living CA9-22 cell is presented to demonstrate the performance of the method. Further, a statistical analysis of the average RI of the nucleoli, the nucleus excluding the nucleoli and the cytoplasm of twenty CA9-22 cells is performed.