Effects of Ultra-High-Pressure Treatment on Chemical Composition and Biological Activities of Free, Esterified and Bound Phenolics from Phyllanthus emblica L. Fruits.

Phyllanthus emblica L. fruits (PEFs) were processed by ultra-pressure (UHP) treatment and then extracted by the ultrasonic-assisted extraction method. The influence of UHP on the phenolic composition, enzyme inhibitory activity and antioxidant activity of the free, esterified, and bound phenolic fractions from PEFs were compared. UHP pretreatment of PEFs significantly increased the total phenolic and flavonoid contents (p < 0.05). A total of 24 chemical compositions were characterized in normal and UHP-treated PEFs by UHPLC-ESI-HRMS/MS. Compared with normal PEFs, these three different phenolic fractions had stronger antioxidant activities and inhibitory effects on the intracellular reactive oxygen species (ROS) production in H2O2-induced HepG2 cells (p < 0.05). The ROS inhibition might be due to an up-regulation of the expressions of superoxide dismutase (SOD) and glutathione (GSH) activities. In addition, these three different phenolic fractions also significantly inhibited the activities of metabolic enzymes, including α-glucosidase, α-amylase and pancreatic lipase. This work may provide some insights into the potential economics and applications of PEFs in food and nutraceutical industries.

Targeted Migration of Human Adipose-Derived Stem Cells to Secondary Lymphoid Organs Enhances Their Immunomodulatory Effect and Prolongs the Survival of Allografted Vascularized Composites.

The targeted delivery of therapeutic agents to secondary lymphoid organs (SLOs), which are the niches for immune initiation, provides an unprecedented opportunity for immune intolerance induction. The alloimmune rejection postvascularized composite allotransplantation (VCA) is mediated by T lymphocytes. Human adipose-derived stem cells (hASCs) possess the superiority of convenient availability and potent immunoregulatory property, but their therapeutic results in the VCA are unambiguous thus far. Chemokine receptor 7 (CCR7) can specifically guide immune cells migrating into SLOs. There, the genes of CCR7-GFP or GFP alone were introduced into hASCs by lentivirus. hASCs/CCR7 maintained the multidifferentiation and immunoregulatory abilities, but it gained the migration capacity elicited by secondary lymphoid organ chemokine (SCL) (CCR7 ligand) in vitro. Noteworthily, intravenously infused hASCs/CCR7 targetedly relocated in the T-cell aggression area in SLOs. In a rat VCA model, hASCs/GFP transfusion had a rare effect on the allografted vascularized composite. However, hASCs/CCR7 infusion potently prolonged the grafts' survival time. The ameliorated pathologic exhibition and the regulated inflammatory cytokines in the peripheral blood were also observed. The altered axis of Th1/Th2 and Tregs/Th17 in SLOs may underlie the downregulated rejection response. Moreover, the proteomic examination of splenic T lymphocytes also confirmed that hASCs/CCR7 decreased the proteins related to cytokinesis, lymphocyte proliferation, differentiation, and apoptotic process. In conclusion, our present study demonstrated that targeted migration of hASCs/CCR7 to SLOs highly intensifies their in vivo immunomodulatory effect in the VCA model for the first time. We believe this SLO-targeting strategy may improve the clinical therapeutic efficacy of hASC for allogeneic and autogenic immune disease. Stem Cells 2019;37:1581-1594.

Non-Gaussian Systems Control Performance Assessment Based on Rational Entropy.

Control loop Performance Assessment (CPA) plays an important role in system operations. Stochastic statistical CPA index, such as a minimum variance controller (MVC)-based CPA index, is one of the most widely used CPA indices. In this paper, a new minimum entropy controller (MEC)-based CPA method of linear non-Gaussian systems is proposed. In this method, probability density function (PDF) and rational entropy (RE) are respectively used to describe the characteristics and the uncertainty of random variables. To better estimate the performance benchmark, an improved EDA algorithm, which is used to estimate the system parameters and noise PDF, is given. The effectiveness of the proposed method is illustrated through case studies on an ARMAX system.

[Retracted] Adipose extracellular matrix promotes skin wound healing by inducing the differentiation of adipose­derived stem cells into fibroblasts.

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the immunohistochemical images shown in Fig. 2B and C on p. 896 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had already been published before this paper was received at International Journal of Molecular Medicine (several of which have been retracted). Moreover, the flow-cytometric data shown in Fig. 2A appeared to be potentially anomalous. In view of the fact that the abovementioned data had already apparently been published prior to the submission of this paper to International Journal of Molecular Medicine, the Editor has decided that the article should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 43: 890-900, 2019; DOI: 10.3892/ijmm.2018.4006].

Evaluation of Rabies Immunoglobulin Administration Status in China: a Retrospective, Cross-Sectional Study at a Tertiary Hospital in Beijing.

This retrospective cross-sectional single-center study included patients with category III exposure to rabies virus between January and December 2019. Exposure characteristics and clinical data were compared and statistically analyzed between groups who were willing and unwilling to receive the rabies immunoglobin (RIG) injection, and the determinants of its administration were identified by stepwise multivariate logistic regression analyses. In total, 1,757 patients with category III exposure were enrolled: 845 men (48.1%) and 912 women (51.9%; median age: 28 [9-50] years). Among them, 1,297 (73.8%) received the RIG injection (median age: 28 [8-50] years) and 460 (26.2%) refused to receive the injection (median age: 25 [15-48] years). Patients aged 16-25 years (odds ratio [OR] = 3.006, 95% confidence interval [CI] = 1.957-4.619), 26-45 years (OR = 2.940, 95% CI = 2.011-4.298), 46-55 years (OR = 3.647, 95% CI = 2.233-5.959), and above 56 years (OR = 6.660, 95% CI = 4.009-11.062); those with injuries caused by cats (OR = 1.937, 95% CI = 1.476-2.542); and people with scratch (OR = 3.319, 95% CI = 2.510-4.390) and minor (OR = 35.281, 95% CI = 18.524-64.198), and moderate (OR = 12.711, 95% CI = 7.221-22.375) injuries were more likely to refuse injection. The RIG administration level in the settings studied herein was found to be insufficient. Educational and awareness programs on rabies prevention, especially those targeted at people not injured by dogs, people with minor injuries, and the elderly should be considered.

Reaction-Diffusion Model-Based Research on Formation Mechanism of Neuron Dendritic Spine Patterns.

The pattern abnormalities of dendritic spine, tiny protrusions on neuron dendrites, have been found related to multiple nervous system diseases, such as Parkinson's disease and schizophrenia. The determination of the factors affecting spine patterns is of vital importance to explore the pathogenesis of these diseases, and further, search the treatment method for them. Although the study of dendritic spines is a hot topic in neuroscience in recent years, there is still a lack of systematic study on the formation mechanism of its pattern. This paper provided a reinterpretation of reaction-diffusion model to simulate the formation process of dendritic spine, and further, study the factors affecting spine patterns. First, all four classic shapes of spines, mushroom-type, stubby-type, thin-type, and branched-type were reproduced using the model. We found that the consumption rate of substrates by the cytoskeleton is a key factor to regulate spine shape. Moreover, we found that the density of spines can be regulated by the amount of an exogenous activator and inhibitor, which is in accordance with the anatomical results found in hippocampal CA1 in SD rats with glioma. Further, we analyzed the inner mechanism of the above model parameters regulating the dendritic spine pattern through Turing instability analysis and drew a conclusion that an exogenous inhibitor and activator changes Turing wavelength through which to regulate spine densities. Finally, we discussed the deep regulation mechanisms of several reported regulators of dendritic spine shape and densities based on our simulation results. Our work might evoke attention to the mathematic model-based pathogenesis research for neuron diseases which are related to the dendritic spine pattern abnormalities and spark inspiration in the treatment research for these diseases.

Combined treatment of melatonin and sodium tanshinone IIA sulfonate reduced the neurological and cardiovascular toxicity induced by deltamethrin in zebrafish.

The pyrethroid insecticide deltamethrin has been reported to have an effect on vertebrate development and cardiovascular disease. Sodium tanshinone IIA sulfonate (STS) is considered to have cardioprotective effects and melatonin is known to regulate sleep-waking cycles. In this experiment, we used transgenic zebrafish Tg (kdrl:mCherry) and Tg (myl7:GFP) to investigate whether STS and melatonin could reverse the cardiovascular toxicity and neurotoxicity induced by deltamethrin. Zebrafish embryos were exposed to 25 µg/L deltamethrin at 10 hpf and treated with 100 mmol/L STS and 1 µmol/L melatonin showed that deltamethrin treatment affected normal cardiovascular development. In situ hybridization and qRT-PCR results showed that deltamethrin could interfere with the normal expression of cardiovascular development-related genes vegfr2, shh, gata4, nkx2.5, causing functional defects in the cardiovascular system. In addition, deltamethrin could affect the sleep-waking behavior of larvae, increasing the activity of larvae, decreasing the rest behavior and the expression of hcrt, hcrtr, aanat2 were down-regulated. The addition of melatonin and STS can significantly alleviate cardiovascular toxicity and sleep-waking induced by deltamethrin, while restoring the expression of related genes to normal levels. Our study demonstrates the role of STS and melatonin in protecting cardiovascular and sleep-waking behavior caused by deltamethrin.

Adipose extracellular matrix promotes skin wound healing by inducing the differentiation of adipose­derived stem cells into fibroblasts.

Fibroblasts are the major effector cells of skin wound healing. Adipose­derived stem cells can differentiate into fibroblasts under certain conditions. In the present study, it was hypothesized that adipose­derived stem cells (ADSCs) could be induced by the adipose extracellular matrix (ECM) to differentiate into fibroblasts in order to promote skin wound healing. First, flow cytometry was used to detect the ratio of fibroblasts and relative expression of the fibroblast markers cytokeratin 19 (CK19) and vimentin in ADSCs. Then, the effect of the adipose ECM during the differentiation of ADSCs into fibroblasts was investigated by detecting the total amount of collagen fibers and degree of fibrosis, and the proliferation and cell cycle of differentiated fibroblasts, using the MTT assay and flow cytometry analysis respectively. Finally, a mouse skin wound model was established and treated with PBS, ADSC suspension or ECM + ADSCs to compare wound healing rate and expression of collagen I and collagen III by immunohistochemistry. Following induction of ADSCs with the adipose ECM, more fibroblasts were found, expression of CK19 and vimentin increased, and a greater degree of fibrosis occurred, which revealed the positive effect of the adipose ECM on the differentiation of ADSCs into fibroblasts. In addition, the induced fibroblasts had enhanced proliferation activity, with more cells in the S phase and fewer in the G2/M phase. The in vivo experiment indicated that the ECM produced by the ADSCs had a faster wound healing rate and increased expression of collagen I and collagen III compared with mice injected with PBS or ADSCs alone, which verified that ADSCs induced by the adipose ECM had a positive effect on skin wound healing. The present study demonstrated that the adipose ECM in combination with ADSCs may be a novel therapeutic target for the repair of skin injury, due to the ability of the adipose ECM to induce the differentiation of ADSCs into fibroblasts and to facilitate the wound healing process.