Ameliorative effects of silybin against avermectin-triggered carp spleen mitochondrial dysfunction and apoptosis through inhibition of PERK-ATF4-CHOP signaling pathway.

The aim of this study was to investigate the splenic tissue damage of environmental biological drug avermectin to freshwater cultured carp and to evaluate the effect of silybin on the splenic tissue damage of carp induced by avermectin. A total of 60 carp were divided into 4 groups with 15 carp in each group, including the control group fed with basic diet, experimental group fed with basal diet and exposed to avermectin (avermectin group), experimental group fed with basal diet supplement silybin (silybin group), and experimental group fed with basal diet supplement silybin and exposed to avermectin (silybin + avermectin group). The whole test period lasted for 30 days, and spleen tissue was collected for analysis. In this study, H&E staining, mitochondrial purification and membrane potential detection, ATP detection, DHE staining, biochemical tests, qPCR, immunohistochemistry, and apoptosis staining were used to evaluate the biological processes of spleen tissue injury, mitochondrial function, oxidative stress, apoptosis, and endoplasmic reticulum stress. The results show that silybin protected carp splenic tissue damage caused by chronic avermectin exposure, decreased mitochondrial membrane potential, decreased ATP content, ROS accumulation, oxidative stress, apoptosis, and endoplasmic reticulum stress. Silybin may ameliorate the splenic tissue damage of cultured freshwater carp caused by environmental biopesticide avermectin by alleviating mitochondrial dysfunction and inhibiting PERK-ATF4-CHOP-driven mitochondrial apoptosis. Adding silybin into the diet becomes a feasible strategy to resist the pollution of avermectin and provides a theoretical basis for creating a good living environment for freshwater carp.

Essential oil from the roots of Paeonia lactiflora pall. has protective effect against corticosterone-induced depression in mice via modulation of PI3K/Akt signaling pathway.

For thousands of years, the roots of Paeonia lactiflora Pall (PLP) has been considered by traditional Chinese medicine as a drug that can improve mental or emotional disorders, including depression, anxiety and affective disorders. Unfortunately, the research on the mechanism of action and active ingredients of this beneficial drug is not comprehensive. This study focused on the activity of essential oil from PLP (EOP), systematically studied the antidepressant effect of EOP for the first time, and discussed the potential mechanism of its antidepressant effect. In this study, we used a mouse model of corticosterone (CORT)-induced depression, and found that EOP had a significant antidepressant effect on the symptoms of CORT-induced depression in mice, and significantly down-regulated the levels of CRH, ACTH and cortisol in the brain tissues of mice. In addition, we found that EOP treatment alleviated CORT-induced hippocampal neuron injury in mice In vitro experiments. It was also found that EOP could inhibit CORT-induced apoptosis and improve the proliferation ability and cell viability of PC12 cells. Further, with the help of network analysis, it was revealed that PI3K-Akt might be one of the main signaling pathways of EOP against CORT-induced hippocampal neuron apoptosis. In this study, we also found that EOP up-regulated the phosphorylation of PI3K and Akt in CORT-induced mouse hippocampal neurons and PC12 cells, and promoted the nuclear transcription of Nrf2 in CORT-induced PC12 cells. In conclusion, with the integrated approach, we demonstrated that EOP exerted anti-apoptotic effects on hippocampal neurons through PI3K/Akt/Nrf2 signaling pathway.

An Initial Study on Multi-Point Laser Acupuncture Based on 2-D Galvo Mirror.

Currently, the majority of commercially available laser acupuncture instruments are still hand-held and only support single-point stimulation. Simultaneous multi-point stimulation improves the therapeutic efficacy of laser acupuncture by stimulating multiple acupoints at the same time. A "2-dimensional (2-D) galvo mirror" was utilized as a positioning laser acupuncture device for multi-acupoints stimulation. Due to its ability to perform 2-D fast scanning, a single laser beam was reflected by the mirror and stimulated multiple acupuncture points simultaneously. This introduction to the new system, presents its architecture, and shows some initial results. This initial stage of development was focused on the acupoints of the human forearm. This proposed system is the first low-cost, noncontact laser acupuncture system that enables continuous multi-acupoint stimulation with a single laser beam. Notably, it is technically feasible to develop this technique into a whole-body laser acupuncture stimulation system.

[Molecular mechanism analysis of Erzhi Wan in treatment of aging based on network pharmacology].

This present study aimed to explore the molecular mechanism of Erzhi Wan(a prescription of nourishing Yin and toni-fying liver and kidney) in treatment of aging by network pharmacology. The active constituents and target proteins of Erzhi Wan were searched from Traditional Chinese Medicine Systems Pharmacology Database(TCMSP) and PubChem databases respectively. Aging-related genes were searched from Gene and HAGR databases. Based on the Ingenuity Pathway Analysis(IPA), we analyzed the common molecular network, biological pathway and interaction sites between these two parts, and verified some of them by Western blot. Twelve active constituents of Erzhi Wan were screened by TCMSP databases, 69 protein targets were predicted through PubChem, and 148 aging-related genes were found in Gene and HAGR databases. IPA comparison showed that the molecular networks of these two were complex, with diversity of biological functions. The common pathways involved 292 pathways, mainly related to tumors. They acted on hypoxia inducible factor-1α gene(HIF1α), nuclear factor-E2 related factor(Nrf2/NFE2 L2), tumor necrosis factor(TNF) and other sites. Western blot results suggested that Erzhi Wan could down-regulate the expression of HIF1α, with statistical difference(P<0.05). It was concluded that, Erzhi Wan could intervene aging through improving pseudo-hypoxic microenvironment and inflammation. The molecular mechanism of Erzhi Wan in delaying aging was preliminarily revealed, which laid a foundation for further stu-dying the anti-aging mechanism of Erzhi Wan, and also provided a reference for the compatibility mechanism and extended application of Chinese medicine compounds.

Effects of the New Lift-Thrust Operation in Laser Acupuncture Investigated by Thermal Imaging.

Acupuncture manipulation is one of the key factors affecting the performance of acupuncture in Traditional Chinese Medicine. Lift-thrust and twirl-twist are two of the most commonly used manipulation methods for needle acupuncture. We previously have developed a novel laser acupuncture model that emulates lift-thrust operation. In this study, we intend to show the effectiveness of such a model by applying it on the Neiguan acupoint (PC6). Stimulation was reported to be beneficial for improving cardiac output and peripheral circulation. Therefore, we hypothesized that the stimulation of laser acupuncture may increase the temperature of the subjects' fingertip due to increased peripheral blood flow. A thermal imager was used to measure the temperature change of subjects' fingertips. Through regression analysis, it has been shown that while PC6 is stimulated, laser acupuncture with lift-thrust operation caused a more rapid, stable, and lasting temperature rise of fingertip than that without lift-thrust operation. On the contrary, we observe no significant temperature change when a sham point nearby PC6 (a point which is not traditionally defined as the acupoint) was stimulated. Our results suggest the emulation of manipulation methods such as the lift-thrust operation could be a potential direction for the future development of laser acupuncture.

A Membrane-Targeted Peptide Inhibiting PtxA of Phosphotransferase System Blocks Streptococcus mutans.

Streptococcus mutans, the primary cause of dental caries, takes up carbohydrates through the phosphoenolpyruvate sugar phosphotransferase system (PTS). This study aimed to identify a novel membrane-targeted antimicrobial peptide (AMP) that could also target the L-ascorbate-specific PtxA component of the S. mutans PTS system. C10-KKWW was identified and selected using virtual screening of a lipopeptide library, a minimum inhibiting concentration (MIC) assay, cytotoxicity assays and a hemolysis assay. Surface plasmon resonance confirmed that C10-KKWW had a high binding affinity for PtxA. Combining with scanning electron microscopy and cell permeability assay, it was shown that the effects of C10-KKWW could be attributed to both membrane and PtxA. Wild type (WT) S. mutans, a ptxA deletion mutant (ΔptxA), and a mutant-complemented strain (CptxA), were cultured consistently in brain heart infusion (BHI) medium, tryptone-vitamin medium supplemented with 15 mM L-ascorbate (TVL), or for 5 h in BHI supplemented with 7.4 mM sodium L-ascorbate. Compared to ∆ptxA, in WT S. mutans and CptxA, C10-KKWW had a stronger MIC (3.9 µg/mL), and distinctively decreased biofilm viability. The extracellular concentrations of L-ascorbate/sodium L-ascorbate were not changed before and after WT treated with C10-KKWW. L-ascorbate-induced operon genes, or other PTS genes, were significantly suppressed by C10-KKWW. In conclusion, C10-KKWW has been developed; it acts through interaction with the bacterial membrane and interferes with L-ascorbate translocation to inhibit S. mutans growth and eradicate its biofilm. C10-KKWW may be especially effective at optimal oral ascorbate levels. A combination of C10-KKWW with sodium L-ascorbate might also be a novel strategy for dental caries treatment.

Hemorrhage detection during focused-ultrasound induced blood-brain-barrier opening by using susceptibility-weighted magnetic resonance imaging.

High-intensity focused ultrasound has been discovered to be able to locally and reversibly increase the permeability of the blood-brain barrier (BBB), which can be detected using magnetic resonance imaging (MRI). However, side effects such as microhemorrhage, erythrocyte extravasations or even extensive hemorrhage may also occur. Although current contrast-enhanced T1-weighted MRI can be used to detect the changes in BBB permeability, its efficacy in detecting tissue hemorrhage after focused-ultrasound sonication remains limited. The purpose of this study is to investigate the feasibility of magnetic resonance susceptibility-weighted imaging (MR-SWI) for identifying possible tissue hemorrhage associated with disruption of the BBB induced by focused ultrasound in a rat model. The brains of 42 Sprague-Dawley rats were subjected to 107 sonications, either unilaterally or bilaterally. Localized BBB opening was achieved by delivering burst-mode focused ultrasound energy into brain tissue in the presence of microbubbles. Rats were studied by T2-weighted and contrast-enhanced T1-weighted MRI techniques, as well as by SWI. Tissue changes were analyzed histologically and the extent of apoptosis was investigated with the terminal deoxynucleotidyl transferase biotin-dUTP nick-end labeling method. The results demonstrated that SWI is more sensitive than standard T2-weighted and contrast-enhanced T1-weighted MRI techniques in detecting hemorrhages after brain sonication. Longitudinal study showed that SWI is sensitive to the recovery process of the damage and, therefore, could provide important and complementary information to the conventional MR images. Potential applications such as drug delivery in the brain might be benefited.