Hydrogen-induced tunable remanent polarization in a perovskite nickelate.

Materials with field-tunable polarization are of broad interest to condensed matter sciences and solid-state device technologies. Here, using hydrogen (H) donor doping, we modify the room temperature metallic phase of a perovskite nickelate NdNiO3 into an insulating phase with both metastable dipolar polarization and space-charge polarization. We then demonstrate transient negative differential capacitance in thin film capacitors. The space-charge polarization caused by long-range movement and trapping of protons dominates when the electric field exceeds the threshold value. First-principles calculations suggest the polarization originates from the polar structure created by H doping. We find that polarization decays within ~1 second which is an interesting temporal regime for neuromorphic computing hardware design, and we implement the transient characteristics in a neural network to demonstrate unsupervised learning. These discoveries open new avenues for designing ferroelectric materials and electrets using light-ion doping.

DDX24 promotes tumor progression by mediating hexokinase-1 induced glycolysis in gastric cancer.

Metabolic reprogramming allows tumor cells to meet high demand of biogenesis and increased energy for rapid proliferation. Gastric cancer (GC) ranks among the most prevalent malignancies globally. Exploring the underlying mechanisms of glycolytic reprogramming in GC could provide new therapeutic target for GC treatment. Here, we showed that DEAD-box helicase 24 (DDX24) played a critical role in hexokinase-1 (HK1) induced glycolysis. DDX24 expression was significantly elevated in GC tissues and was closely associated with worse survival in GC patients. In addition, DDX24 promoted glucose uptake and lactate production in GC cells. Mechanistically, DDX24 could bind the HK1 mRNA and positively regulated HK1 level at the transcriptional level. Moreover, DDX24 promoted the proliferation, migration, and invasion ability of GC cells by upregulating HK1. Collectively, these results suggested that DDX24 was a critical player in the regulation of glycolytic reprogramming and also implicated DDX24 as a valuable therapeutic target for GC.

The Influence of PRO-SELF Cancer Pain Control Programme on Patients' Self-Management Ability.

Objective: Recently, cancer patients have challenges with self-management. This study aims to improve symptoms of chronic pain, and anxiety and depression associated with cancer by PRO-SELF nursing intervention. Methods: Sixty-four patients were randomly assigned to an intervention and a control group from Jan 2016 to Dec 2019, 34 usable cases in the intervention group and 30 cases in the control group were collected. The control group received a routine cancer pain nursing intervention, whereas the intervention group received a PRO-SELF based multidisciplinary collaborative cancer pain nursing intervention. After three months of intervention, the Numeric Rating Scale (NRS), Medication Compliance Questionnaire (MCQ), Social Support Rating Scale (SSRS), Self-rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS), Quality of Life Scale (FACT-G Chinese version) and Chronic Pain Self-efficacy Scale were resent to compare the differences in the observation indicators included evaluation of patients' social support degree, anxiety and depression score, quality of life scores and self-efficacy scores between two groups. The t-test and rank-sum test were used for statistic analysis. Results: No significant differences were found between groups for pain and medication compliance (P > 0.05). However, significant differences were found between groups in social support, life quality, chronic pain self-efficacy, and self-rating anxiety and depression index scores (P < 0.001). The intervention group report more social support, pain self-efficacy and less anxiety and depression (P < 0.001). Conclusion: The PRO-SELF pain symptoms in patients with a cancer pain management programme improved degree of social support, life quality, self-efficacy, anxiety, depression which is worthy of clinical application.

Research trends of omics in ulcerative colitis: A bibliometric analysis.

Background: Omics has emerged as a promising biological science to shed light on the etiology, pathogenesis, and treatment of ulcerative colitis (UC). At present, although research on the omics of UC has drawn global attention, there is still a lack of bibliometric analysis in this field. This study aimed to access the trends and hotspots of omics in UC research. Method: Publications related to omics in UC from 1 January 2000 to 15 October 2022 were retrieved from the Web of Science Core Collection database. VOSviewer, CiteSpace, and the online bibliometric analysis platform "Bibliometrix" were adopted to extract and visualize information. Results: A total of 385 publications were finally included and the annual number of publications fluctuated. The trend in publications increased rapidly after 2019. The United States showed its dominant position in several publications, total citations, and international collaborations. The top five research organizations for publications on the research of omics in UC were Harvard Medical School, the Icahn School of Medicine at Mount Sinai, Karolinska Institutet, the Brigham and Women's Hospital, and the Massachusetts General Hospital. Ashwin Ananthakrishnan from the Massachusetts General Hospital was the most productive author, and Séverine Vermeire from the Catholic University of Leuven was co-cited most often. Inflammatory bowel disease was the most popular and co-cited journal in this field. The reference with citation bursts and trend topics showed that "ulcerative colitis," "inflammatory bowel disease," "microbiome," "transcriptomics," "genomics," "metabolomics," "proteomics," "dysbiosis," "biomarkers," "loci," and "therapy" are currently research hotspots. Conclusion: Our study presents several important insights into the research trends and developments in the field of omics in UC, which will provide key information for further research.

Surgical methods influence on the risk of anastomotic fistula after pancreaticoduodenectomy: a systematic review and network meta-analysis.

BACKGROUND: Pancreaticoduodenectomy is the first choice surgical intervention for the radical treatment of pancreatic tumors. However, an anastomotic fistula is a common complication after pancreaticoduodenectomy with a high mortality rate. With the development of minimally invasive surgery, open pancreaticoduodenectomy (OPD), laparoscopic pancreaticoduodenectomy (LPD), and robotic pancreaticoduodenectomy (RPD) are gaining interest. But the impact of these surgical methods on the risk of anastomosis has not been confirmed. Therefore, we aimed to integrate relevant clinical studies and explore the effects of these three surgical methods on the occurrence of anastomotic fistula after pancreaticoduodenectomy. METHODS: A systematic literature search was conducted for studies reporting the RPD, LPD, and OPD. Network meta-analysis of postoperative anastomotic fistula (Pancreatic fistula, biliary leakage, gastrointestinal fistula) was performed. RESULTS: Sixty-five studies including 10,026 patients were included in the network meta-analysis. The rank of risk probability of pancreatic fistula for RPD (0.00) was better than LPD (0.37) and OPD (0.62). Thus, the analysis suggests the rank of risk of the postoperative pancreatic fistula for RPD, LPD, and OPD. The rank of risk probability for biliary leakage was similar for RPD (0.15) and LPD (0.15), and both were better than OPD (0.68). CONCLUSIONS: This network meta-analysis provided ranking for three different types of pancreaticoduodenectomy. The RPD and LPD can effectively improve the quality of surgery and are safe as well as feasible for OPD.

Acinar ATP8b1/LPC pathway promotes macrophage efferocytosis and clearance of inflammation during chronic pancreatitis development.

Noninflammatory clearance of dying cells by professional phagocytes, termed efferocytosis, is fundamental in both homeostasis and inflammatory fibrosis disease but has not been confirmed to occur in chronic pancreatitis (CP). Here, we investigated whether efferocytosis constitutes a novel regulatory target in CP and its mechanisms. PRSS1 transgenic (PRSS1Tg) mice were treated with caerulein to mimic CP development. Phospholipid metabolite profiling and epigenetic assays were performed with PRSS1Tg CP models. The potential functions of Atp8b1 in CP model were clarified using Atp8b1-overexpressing adeno-associated virus, immunofluorescence, enzyme-linked immunosorbent assay(ELISA), and lipid metabolomic approaches. ATAC-seq combined with RNA-seq was then used to identify transcription factors binding to the Atp8b1 promoter, and ChIP-qPCR and luciferase assays were used to confirm that the identified transcription factor bound to the Atp8b1 promoter, and to identify the specific binding site. Flow cytometry was performed to analyze the proportion of pancreatic macrophages. Decreased efferocytosis with aggravated inflammation was identified in CP. The lysophosphatidylcholine (LPC) pathway was the most obviously dysregulated phospholipid pathway, and LPC and Atp8b1 expression gradually decreased during CP development. H3K27me3 ChIP-seq showed that increased Atp8b1 promoter methylation led to transcriptional inhibition. Atp8b1 complementation substantially increased the LPC concentration and improved CP outcomes. Bhlha15 was identified as a transcription factor that binds to the Atp8b1 promoter and regulates phospholipid metabolism. Our study indicates that the acinar Atp8b1/LPC pathway acts as an important "find-me" signal for macrophages and plays a protective role in CP, with Atp8b1 transcription promoted by the acinar cell-specific transcription factor Bhlha15. Bhlha15, Atp8b1, and LPC could be clinically translated into valuable therapeutic targets to overcome the limitations of current CP therapies.

The Effects of mHealth-Based Gamification Interventions on Participation in Physical Activity: Systematic Review.

BACKGROUND: It is well known that regular physical exercise has associated benefits; yet, participation remains suboptimal. Mobile health (mHealth) has become an indispensable medium to deliver behavior change interventions, and there is a growing interest in the gamification apps in mHealth to promote physical activity (PA) participation. Gamification could use game design elements (such as points, leaderboards, and progress bars), and it has the potential to increase motivation for PA and engagement. However, mHealth-based gamification interventions are still emerging, and little is known about the application status and efficacy of such interventions. OBJECTIVE: This systematic review aims to investigate gamification apps in mHealth for improving PA levels and simultaneously summarize the impact of gamification interventions on PA participation. METHODS: We searched PubMed, Scopus, Web of Science, Embase, CINAHL (EBSCO host), and IEEE Xplore from inception to December 20, 2020. Original empirical research exploring the effects of gamification interventions on PA participation was included. The papers described at least one outcome regarding exercise or PA participation, which could be subjective self-report or objective indicator measurement. Of note, we excluded studies about serious games or full-fledged games. RESULTS: Of 2944 studies identified from the database search, 50 (1.69%) were included, and the information was synthesized. The review revealed that gamification of PA had been applied to various population groups and broadly distributed among young people but less distributed among older adults and patients with a disease. Most of the studies (30/50, 60%) combined gamification with wearable devices to improve PA behavior change, and 50% (25/50) of the studies used theories or principles for designing gamified PA interventions. The most frequently used game elements were goal-setting, followed by progress bars, rewards, points, and feedback. This review demonstrated that gamification interventions could increase PA participation; however, the results were mixed, and modest changes were attained, which could be attributed to the heterogeneity across studies. CONCLUSIONS: Overall, this study provides an overview of the existing empirical research in PA gamification interventions and provides evidence for the efficacy of gamification in enhancing PA participation. High-quality empirical studies are needed in the future to assess the efficacy of a combination of gamification and wearable activity devices to promote PA, and further exploration is needed to investigate the optimal implementation of these features of game elements and theories to enhance PA participation.

Diagnostic accuracy of convolutional neural network-based endoscopic image analysis in diagnosing gastric cancer and predicting its invasion depth: a systematic review and meta-analysis.

BACKGROUND AND AIMS: This study aimed to evaluate the accuracy and effectiveness of the convolutional neural network (CNN) in diagnosing gastric cancer and predicting the invasion depth of gastric cancer and to compare the performance of the CNN with that of endoscopists. METHODS: PubMed, Embase, Web of Science, and gray literature were searched until July 23, 2021 for studies that assessed the diagnostic accuracy of CNN-assisted examinations for gastric cancer or the invasion depth of gastric cancer. Studies meeting inclusion criteria were included in the systematic review and meta-analysis. RESULTS: Seventeen studies comprising 51,446 images and 174 videos of 5539 patients were included. The pooled sensitivity, specificity, positive likelihood ratio (LR+), negative likelihood ratio (LR-), and area under the curve (AUC) of the CNN for diagnosing gastric cancer were 89% (95% confidence interval [CI], 85-93), 93% (95% CI, 88-97), 13.4 (95% CI, 7.3-25.5), .11 (95% CI, .07-.17), and .94 (95% CI, .91-.98), respectively. The performance of the CNN in diagnosing gastric cancer was not significantly different from that of expert endoscopists (.95 vs .90, P > .05) and was better than that of overall endoscopists (experts and nonexperts) (.95 vs .87, P < .05). The pooled sensitivity, specificity, LR+, LR-, and AUC of the CNN for predicting the invasion depth of gastric cancer were 82% (95% CI, 78-85), 90% (95% CI, 82-95), 8.4 (95% CI, 4.2-16.8), .20 (95% CI, .16-.26), and .90 (95% CI, .87-.93), respectively. CONCLUSIONS: The CNN is highly accurate in diagnosing gastric cancer and predicting the invasion depth of gastric cancer. The performance of the CNN in diagnosing gastric cancer is not significantly different from that of expert endoscopists. Studies of the real-time performance of the CNN for gastric cancer diagnosis are needed to confirm these findings.

Comparative efficacy of non-pharmacological interventions on behavioural and psychological symptoms in elders with dementia: A network meta-analysis.

AIM: To explore the best non-pharmaceutical interventions for improving the behavioural and psychological symptoms in elders with dementia. DESIGN: Bayesian network meta-analysis. METHODS: A comprehensive electronic literature search was performed in five English databases and four Chinese databases to identify relevant randomized controlled trials (RCTs) that were published up to 31 October 2019. RESULTS: A total of 41 RCTs were included in this network meta-analysis involving 5 different non-pharmacological interventions: therapeutic recreation (TC), reminiscence therapy (RT), behaviour therapy (BT), massage therapy (MT) and individualized nursing (IN).The results of network meta-analysis showed that individualized nursing was the best in improving depression, cognitive function, and activities of daily living of behavioural and psychological symptoms of dementia. Behaviour therapy was the best in improving anxiety symptoms. Reminiscence therapy was the best in improving neuropsychiatric symptoms.

Role of the intelligent exercise rehabilitation management system on adherence of cardiac rehabilitation in patients with coronary heart disease: a randomised controlled crossover study protocol.

INTRODUCTION: The benefits of cardiac rehabilitation (CR) on the reduction of cardiac and all-cause mortality are well documented. However, adherence remains suboptimal in China. It is clear that traditional CR does not meet the needs of many eligible patients and innovation is required to improve its application. Home-based CR (HBCR) is a cost-effective method that may be a valuable alternative for many individuals in China. In HBCR, it is often difficult to maintain an exercise intensity that is both effective and within safe limits, factors that are essential for patient safety. Mobile health interventions have the potential to overcome these obstacles and may be efficacious in improving adherence. The purpose of this study is to evaluate whether an Intelligent Exercise Rehabilitation Management System (IERMS)-based HBCR could improve adherence to CR and to assess the effects on exercise capacity, mental health, self-efficacy, quality of life and lifestyle-related risk factors. METHODS AND ANALYSIS: We propose a single-blinded, two-arm, randomised controlled crossover study of 70 patients with coronary heart disease (CHD). Participants will be randomly assigned in a 1:1 ratio to one of the two groups. Patients in group 1 will receive the IERMS intervention together with usual care for the first 6 weeks and usual care for the last 6 weeks, while patients assigned to group 2 will receive usual care for the first 6 weeks and will use IERMS in the last 6 weeks. The primary outcome is adherence to the programme and secondary outcomes include exercise capacity, psychological well-being, quality of life, self-efficacy and lifestyle-related risk factors. All secondary outcomes will be measured at baseline, 6 weeks and 12 weeks. ETHICS AND DISSEMINATION: This study has been approved by the Human Research Ethics Committee of the School of Nursing, Jilin University (HREC 2019120901). The results will be published in peer-reviewed journals and at conferences. TRIAL REGISTRATION NUMBER: ChiCTR1900028182; Pre-results.

Photocontrolled Iodine-Mediated Reversible-Deactivation Radical Polymerization: Solution Polymerization of Methacrylates by Irradiation with NIR LED Light.

Herein, near-infrared (NIR) photocontrolled iodide-mediated reversible-deactivation radical polymerization (RDRP) of methacrylates, without an external photocatalyst, was developed using an alkyl iodide (e.g., 2-iodo-2-methylpropionitrile) as the initiator at room temperature. This example is the first use of a series of special solvents containing carbonyl groups (e.g., 1,3-dimethyl-2-imidazolidinone) as both solvent and catalyst for photocontrolled RDRP using long-wavelength (λmax =730 nm) irradiation. The polymerization system comprises monomer, alkyl iodide initiator, and solvent. Well-defined polymers were synthesized with excellent control over the molecular weights and molecular weight distributions (Mw /Mn <1.21). The living features of this system were confirmed by polymerization kinetics, multiple controlled "on-off" light switching cycles, and chain extension experiments. Importantly, the polymerizations proceeded successfully with various barriers (pork skin and A4 paper), demonstrating the advantage of high-penetration NIR light.

Tailoring Morphologies, Photocatalytic Activity, and Energy Bands of Bi25FeO40 via Valence State Transformation of Doped V Ions.

Photocatalysts with suitable nanostructures and excellent photocatalytic activity driven by solar light are in great demand for rapidly eliminating the organic pollutants from wastewater. In order to improve the photocatalytic activities, three main factors should be considered, including band gap, band structure, and morphologies. Most of the previous studies only focused on manipulating one factor, such as the band gap by element doping. However, studies on enhancing photocatalytic activities by designing the band structure and morphologies are challenging, due to the difficulity to control the three parameters at the same time. Here, the V-doped Bi25FeO40 (Bi25Fe1- xV xO40) was demonstrated as a great system to manipulate the photocatalytic activities by designing the band structure and morphologies. With the simple hydrothermal methods, Bi25Fe1- xV xO40 with different flower-like morphologies and band structures were prepared. Surprisingly, the blooming and withering processes of the artificial architectures could be precisely tuned through different V concentrations. The controllable microstructures possess the high visible light absorption and enhanced photocatalytic activity. These results offer a model to reveal how the doping element can synchronously manipulate the particle morphology, band gap, and band structures, which is a key step to design new photocatalytic materials.

Photocontrolled Iodine-Mediated Green Reversible-Deactivation Radical Polymerization of Methacrylates: Effect of Water in the Polymerization System.

Photocontrolled iodine-mediated reversible-deactivation radical polymerization (RDRP) is a facile and highly efficient access to precision polymers. Herein, a facile photocontrolled iodine-mediated green RDRP strategy was successfully established in water by using 2-iodo-2-methylpropionitrile (CP-I) as the initiator and water-soluble functional monomers including poly(ethylene glycol) methyl ether methacrylate (PEGMA), 2-hydroxyethyl methacrylate (HEMA), and 2-hydroxypropyl methacrylate (HPMA) as the model monomers under blue-light-emitting diode (LED) irradiation at room temperature. Well-defined polymers (PPEGMA, PHEMA, PHPMA) with narrow polydispersities (1.09-1.21) were obtained, and amphiphilic block copolymers which can form nanospheres in situ in water (PPEGMA-b-poly(benzyl methacrylate) (PPEGMA-b-PBnMA) and PPEGMA-b-PHPMA) were prepared. To explore the role of water in our polymerization, control experiments were successfully carried out by using oil-soluble monomer methyl methacrylate (MMA) with the help of trace amounts of water. Notably, the green solvent-water-has an additionally positive effect in accelerating the polymerization and makes our polymerization system an environmentally friendly polymerization system. Therefore, this simple strategy conducted in the presence of water enables the green preparation of well-defined water-soluble or water-insoluble polymers and clean synthesis of amphiphilic copolymer nanoparticles in situ.

Nux Vomica Exposure Triggered Liver Injury and Metabolic Disturbance in Zebrafish Larvae.

Zebrafish larvae were used to further understand the liver toxicity of nux vomica. The histopathology, protein expression, and gene expression were assessed to confirm apoptosis in the liver, and then, profiles of the metabolites in zebrafish were investigated by untargeted metabolomic assessment to understand the potential toxicity mechanism of nux vomica. Histopathological observations showed that nux vomica caused damage to liver cells. Western blot results indicated increased expression of activated caspase3, and the result of real-time polymerase chain reaction showed a significant increase in the expression level of caspase-3, caspase-8, and caspase-9 genes (p < 0.05) compared with the control group. The liver injury from nux vomica was linked to the downregulation of amino acid (e.g., proline and alanine) and fatty acid (e.g., palmitoleic acid) metabolism and upregulation of some other fatty acid (e.g., arachidic acid) and purine (e.g., xanthine and uric acid) metabolism. The hepatotoxicity of nux vomica resulted from metabolic pathway disturbances, including small molecules involved in energy, purine, lipids, and amino acid metabolism.

Organocatalytic Approach to Functional Semifluorinated Polymers Driven by Visible Light.

Through the construction of an organic photocatalysis system, photoredox catalyst (PC)/additive, where PC stands for photoredox catalyst, an organocatalyzed step transfer-addition and radical-termination (O-START) polymerization irradiated by blue LED light at room temperature is realized. Different types of α,ω-diiodoperfluoroalkane A and α,ω-unconjugated diene B are copolymerized through O-START efficiently, and generate various kinds of functional semifluorinated polymers, including polyolefins and polyesters. The process is affected by several factors; solvents, additives, and feed ratio of A to B. After optimization of all these components, the polymerization efficiency is greatly improved, generating polymers with both relatively high yield and molecular weight. Considering the mild reaction condition, easy operation process, and free-of-metal-catalyst residues in the polymer product, the organocatalytic polymerization strategy provides a simple and efficient approach to functional semifluorinated polymer materials and hopefully opens up their application in high-tech fields.

Anti-angiogenic activity of water extract from Euphorbia pekinensis Rupr.

ETHNOPHARMACOLOGICAL RELEVANCE: Euphorbia pekinensis Rupr. (EP) is a Euphorbia species of Euphorbiaceae, which is widely used in traditional Chinese medicine. It has been reported to exhibit therapeutic effects on solid tumors, leukemias, and malignant ascites although underlying molecular mechanisms are poorly delineated. Anti-angiogenic therapy is a recognized strategy for treating cancer-based solid tumors, and is also associated with malignant ascites treatment. STUDY AIM: To study the anti-angiogenic properties of the water extract of EP vinegar preparation (WEVEP). MATERIALS AND METHODS: Following WEVEP treatment, intersegmental blood vessels were assessed during the development of transgenic Tg (flk: mCherry) zebrafish as was the proliferation, migration and network formation of HUVECs in vitro. mRNA expression of specific angiogenic-related genes including VEGF family members, Met, and NRP2 was also measured using quantitative real-time PCR (Q-PCR). RESULTS: Data demonstrated that angiogenesis was inhibited by the WEVEP in zebrafish (from 100µg/mL to 250µg/mL, p < 0.0001) and in the HUVEC model (from 100µg/mL to 400µg/mL, p < 0.0001). In the zebrafish model, the mean vessel numbers of administered groups were 26.00 ± 1.29 (100µg/mL), 24.54 ± 2.20 (150µg/mL), 22.66 ± 2.68 (200µg/mL), 20.80 ± 1.75 (250µg/mL), compared to 27.67 ± 0.96 of control group. Relative quantitative gene expression in zebrafish treated with WEVEP demonstrated that only VEGFR3 was significantly increased and other 23 genes including Met, VEGFA, Flt-1 were significantly decreased. CONCLUSION: WEVEP can positively modulate angiogenesis via multiple targeting mechanisms. Our novel results contribute towards the discovery of a possible mechanism(s) of the traditional use of EP in the treatment of cancer and malignant ascites.

Class A Scavenger Receptor Exacerbates Osteoclastogenesis by an Interleukin-6-Mediated Mechanism through ERK and JNK Signaling Pathways.

Osteoclasts originate from bone marrow monocyte/macrophage lineage cells, which are important for bone health. Class A scavenger receptor (SR-A) is a multifunctional molecule that functions during differentiation of monocyte into macrophages and osteoclasts. To further characterize the role of SR-A in osteoclasts, we used the murine tooth movement model (TM) and the murine anterior cruciate ligament transection model of osteoarthritis (ACLT OA). In these two models the bones involved are of different origin and have different properties. Bone resorption was decreased in SR-A-/- mice compared to SR-A+/+ mice. Further evaluation showed that the number of multinucleated osteoclasts in SR-A-/- mice, compared to SR-A+/+ mice, was significantly decreased both in vivo and in vitro. The levels of interleukin-6 (IL-6) produced by osteoclasts were reduced in SR-A-/- mice compared to SR-A+/+ mice. In the in vitro marrow-derived osteoclast formation assay and in both mouse models, osteoclastogenesis was restored to normal in SR-A-/- mice by administration of recombinant murine IL-6. Moreover, neutralization of IL-6 reduced the number of osteoclasts formed in SR-A+/+ mice of TM model. Both extracellular signal-regulated kinase (ERK) and c-Jun N-terminal protein kinase (JNK), but not p38, signaling pathways were downregulated in receptor activator of nuclear factor-κB ligand (RANKL)-stimulated SR-A-/- osteoclasts. Importantly, when treated with either ERK or JNK inhibitor, the numbers of osteoclasts generated from RANKL-induced bone marrow derived-macrophages of SR-A+/+ mice, and their IL-6 production, were significantly decreased. This suggests that SR-A activates the ERK and JNK signaling pathways, and promotes production of IL-6 by osteoclasts to further stimulate osteoclast formation.

Zebrafish model for assessing induced organ toxicity by Strychnos nux-vomica.

OBJECTIVE: To assess the acute organ toxicity of Strychnos nux-vomica with zebrafish model visually. METHODS: To assess acute toxicity, we initially determined the lethal concentration after Strychnos nux-vomica treatment for 24 h. Zebrafish was treated with five concentrations ≦ LC10 for 24 h, and the effects of Strychnos nux-vomica on morphology, function of heart, central nervous system, liver, kidney and organ-specific cell death were assessed. Next, we assessed the reversibility of toxic effect. RESULTS: Strychnos nux-vomica has an effect on the different organs of zebrafish, including heart, central nervous system, liver, and kidney, and cadiotoxicity induced by Strychnos nux-vomica was reversible to some extent. CONCLUSION: Zebrafish model is suitable for confirming the toxic target organs for Chinese traditional medicine.

[Protective role of γδ T cells in concanavalin A-induced liver injury].

OBJECTIVE: To investigate the role played by γδ T cells in acute liver injury using the concanavalin A (ConA)-induced liver injury mouse model. METHODS: Acute liver injury was induced by intravenous injection of 10 mug/g of ConA into male C57BL/6J mice with wild-type or T cell receptor-γ knockout (TCR δ-/-) genetic backgrounds. Mice injected with PBS alone served as negative controls. The degree of liver damage was assessed by measuring serum levels of transaminase and cytokines at post-injection hours 3, 6, 12, 24, 48, and 72. The percentage of γδ T cells and proportions of different subsets in liver lymphocytes were measured by flow cytometry. RESULTS: The TCR δ-/- mice showed significantly higher levels of the inflammatory cytokines IFN-γ, TNFα and IL-4 than the wild-type mice at post-injection hour 3. The percentage of liver γδ T cells increased with increased injury degree, and the extent of increase was significantly higher in the TCR δ-/- mice than the wild-type mice (post-injection hour 6: 6302.61+/-592.06 vs. 1319.26+/-355.48, 12: 6569.44+/-1060.98 vs. 3415.53+/-343.90, 24: 6514.29+/-757.26 vs. 2062.73+/-365.67, 48: 1262.61+/-558.07 vs. 113.66+/-113.26, and 72: 226.54+/-98.20 vs. 42.35+/-21.51 U/L; all P less than 0.05). In addition, compared to the negative control mice, the ConA-induced mice showed a higher proportions of Vγ4 γδ T cells to total γδ T cells (17.78+/-2.95 vs. 25.26+/-2.43) and to total liver lymphocytes (0.47+/-0.07 vs. 0.66+/-0.05). Similarly, compared to the negative control mice, the ConA-induced mice showed a higher proportion of Vγ1 γδ T cells to total γδ T cells (38.37+/-6.10 vs. 50.19+/-5.52) but the proportion to total liver lymphocytes was not significantly different among the groups (0.76+/-0.18 vs. 0.78+/-0.25). Reinfusion of Vγ4 γδ T lymphocytes into TCR δ-/- mice led to lower serum ALT levels than reinfusion of Vγ1 γδ T lymphocytes (5054.10+/-1748.51 vs. 12333.56+/-663.535 U/L). CONCLUSION: γδ T cells play a protective role in ConA-induced liver injury and this effect maybe mediated by the Vγ4 γδ T cell subset.