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Background: Biphasic waveforms are superior to monophasic waveforms for the termination of ventricular fibrillation (VF). However, whether triphasic waveforms are more effective than biphasic ones is still controversial. In the present study, we investigated the effects of second and third phase duration of triphasic rectangle waveform on defibrillation efficacy in a rabbit model of VF.Methods: VF was electrically induced and untreated for 30s in 20 New Zealand rabbits. A defibrillatory shock was applied with one of the 7 waveforms: 6 triphasic rectangle waveforms and a biphasic rectangle waveform. The triphasic waveforms had identical first duration but with different second and third phase durations. A 5 step up-and-down protocol was utilized for determining the defibrillation threshold (DFT). After a 5min interval, the procedure was repeated. A total of 35 cardiac arrest events and defibrillations were investigated for each animal.Results: Two triphasic waveforms with identical first and second phase duration but shorter third phase duration had significantly lower DFT energy than biphasic waveform (0.57±0.18J vs. 0.80±0.28J, p=0.001; 0.60±0.18J vs. 0.80±0.28J, p=0.003). However, no statistical difference in DFT energy was observed between the two triaphsic waveforms that had identical phase duration but different voltages (0.57±0.18J vs. 0.60±0.18J, p=0.638).Conclusions: Phase durations played a main role on defibrillation success for triphasic rectangle waveforms. The optimal triphasic rectangle waveforms that composed of identical second and first phase durations but with shorter third pulse were superior to biphasic rectangle waveform for ventricular defibrillation. [ABSTRACT FROM AUTHOR]

Brassica juncea chitinase is an endo-acting, pathogenesis-related protein that is classified into glycoside hydrolase family 19, with highest homology (50–60%) in its catalytic domain to class I plant chitinases. Here we report X-ray structures of the chitinase catalytic domain from wild-type ( apo, as well as with chloride ions bound) and a Glu234Ala mutant enzyme, solved by molecular replacement and refined at 1.53, 1.8 and 1.7 Å resolution, respectively. Confirming our earlier mutagenesis studies, the active-site residues are identified as Glu212 and Glu234. Glu212 is believed to be the catalytic acid in the reaction, whereas Glu234 is thought to have a dual role, both activating a water molecule in its attack on the anomeric carbon, and stabilizing the charged intermediate. The molecules in the various structures differ significantly in the conformation of a number of loops that border the active-site cleft. The differences suggest an opening and closing of the enzyme during the catalytic cycle. Chitin is expected to dock first near Glu212, which will protonate it. Conformational changes then bring Glu234 closer, allowing it to assist in the following steps. These observations provide important insights into catalysis in family 19 chitinases. [ABSTRACT FROM AUTHOR]

This article presents a case of a 43-year-old man with paradoxical embolism. The patient had simultaneous deep venous thrombosis, pulmonary embolism and bilateral limb-threatening arterial occlusions. The unifying diagnosis was paradoxical embolism through a previously undetected atrial septal defect. Suggestions for the evaluation and emergency management of paradoxical embolism are outlined, and the literature is briefly reviewed. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract. In this issue of Immunity, Griseri et al. (2012) show that IL-23-induced dysregulation of hematopoietic stem and progenitor cells contributes to the pathogenesis of two IBD models. [ABSTRACT FROM AUTHOR]

• Multi-step IR spectroscopy was developed to identify three Rhodiola species containing 31 samples. • Main components of Rhodiola were characterized by multi-step IR fingerprints. • Differences and similarities were unambiguously indicated in IR spectra and multivariate data analysis. • Excellent sensitivity and specificity were displayed in chemometric analysis. Identification of Rhodiola species was the key to ensure the clinical application of Rhodiola , especially in the dried and powdered forms, owing to different Rhodiola species having important differences in the quality and physiological activity of medicinal materials. In this study, multi-step IR spectroscopy combined with multivariate data analysis was employed to establish a on-destructive, fast, and efficient Rhodiola classification method. A total of 31 batches of powder spectra were obtained from three Rhodiola species by FT-IR, including Rhodiola crenulata , R. kirilowii , and R. fastigiata. Then, characteristic peak positions, intensities and shapes obtained from FT-IR, SD-IR and 2D-IR spectra provided valuable information for identifying samples from different Rhodiola species. Multivariate data analysis method including principal component analysis (PCA) and partial least squares discriminant analysis (PLS-DA) was used to achieve discrimination. The results indicated that the combination of multi-step IR spectroscopy and multivariate data analysis was a fast, effective and non-destructive method for identifying and distinguishing of medicinal powder of three different Rhodiola species. This method could be applied to identify confusing traditional Chinese medicine and traditional Tibetan medicine, avoid misuse and adulteration, and ensure the safety and effectiveness of clinical medication. [ABSTRACT FROM AUTHOR]

Lung adenocarcinoma (LUAD) is the most prevalent and aggressive subtype of lung cancer, exhibiting a dismal prognosis with a five-year survival rate below 5%. DEAD-box RNA helicase 18 (DDX18, gene symbol DDX18), a crucial regulator of RNA metabolism, has been implicated in various cellular processes, including cell cycle control and tumorigenesis. However, its role in LUAD pathogenesis remains elusive. This study demonstrates the significant upregulation of DDX18 in LUAD tissues and its association with poor patient survival (from public databases). Functional in vivo and in vitro assays revealed that DDX18 knockdown potently suppresses LUAD progression. RNA sequencing and chromatin immunoprecipitation experiments identified cyclin-dependent kinase 4 (CDK4), a cell cycle regulator, as a direct transcriptional target of DDX18. Notably, DDX18 depletion induced G1 cell cycle arrest, while its overexpression promoted cell cycle progression even in normal lung cells. Interestingly, while the oncogenic protein c-Myc bound to the DDX18 promoter, it did not influence its expression. Collectively, these findings establish DDX18 as a potential oncogene in LUAD, functioning through the CDK4-mediated cell cycle pathway. DDX18 may represent a promising therapeutic target for LUAD intervention. [ABSTRACT FROM AUTHOR]

Neuregulin-1 (Nrg1, gene symbol: Nrg1), a ligand of the ErbB receptor family, promotes intestinal epithelial cell proliferation and repair. However, the dynamics and accurate derivation of Nrg1 expression during colitis remain unclear. By analyzing the public single-cell RNA-sequencing datasets and employing a dextran sulfate sodium (DSS)-induced colitis model, we investigated the cell source of Nrg1 expression and its potential regulator in the process of epithelial healing. Nrg1 was majorly expressed in stem-like fibroblasts arising early in mouse colon after DSS administration, and Nrg1–Erbb3 signaling was identified as a potential mediator of interaction between stem-like fibroblasts and colonic epithelial cells. During the ongoing colitis phase, a significant infiltration of macrophages and neutrophils secreting IL-1β emerged, accompanied by the rise in stem-like fibroblasts that co-expressed Nrg1 and IL-1 receptor 1. By stimulating intestinal or lung fibroblasts with IL-1β in the context of inflammation, we observed a downregulation of Nrg1 expression. Patients with inflammatory bowel disease also exhibited an increase in NRG1+IL1R1+ fibroblasts and an interaction of NRG1–ERBB between IL1R1+ fibroblasts and colonic epithelial cells. This study reveals a novel potential mechanism for mucosal healing after inflammation-induced epithelial injury, in which inflammatory myeloid cell-derived IL-1β suppresses the early regeneration of intestinal tissue by interfering with the secretion of reparative neuregulin-1 by stem-like fibroblasts. [ABSTRACT FROM AUTHOR]

Dectin-1, the receptor for beta-glucans, protects host from fungal infection. However, the role of Dectin-1 in intestinal immunity has not been elucidated completely. We found that Dectin-1-deficient (Clec7a−/−) mice were refractory to both dextran sodium sulfate (DSS)- and CD45RBhiCD4+ T cell-induced colitis associated with an increase of regulatory T (Treg) cells. The proportion of lactobacilli, especially Lactobacillus murinus ( L. murinus ), in commensal microflora was increased in Clec7a−/− mouse colon due to accompanied by a decrease of a group of antimicrobial peptides induced by Dectin-1 signaling. L. murinus colonization increased Treg cells in the colon. Oral administration of laminarin, a Dectin-1 antagonist, suppressed the development of DSS-colitis, associated with the increase of L. murinus and Treg cells. The proportion of closely related Lactobacillus species was decreased in inflammatory bowel disease patients. These observations suggest that Dectin-1 regulates the homeostasis of intestinal immunity by controlling Treg cell differentiation through modification of microbiota. [ABSTRACT FROM AUTHOR]

Background: Oxidative stress (OS) is a key pathophysiological mechanism in Crohn's disease (CD). OS-related genes can be affected by environmental factors, intestinal inflammation, gut microbiota, and epigenetic changes. However, the role of OS as a potential CD etiological factor or triggering factor is unknown, as differentially expressed OS genes in CD can be either a cause or a subsequent change of intestinal inflammation. Herein, we used a multi-omics summary data-based Mendelian randomization (SMR) approach to identify putative causal effects and underlying mechanisms of OS genes in CD. Methods: OS-related genes were extracted from the GeneCards database. Intestinal transcriptome datasets were collected from the Gene Expression Omnibus (GEO) database and meta-analyzed to identify differentially expressed genes (DEGs) related to OS in CD. Integration analyses of the largest CD genome-wide association study (GWAS) summaries with expression quantitative trait loci (eQTLs) and DNA methylation QTLs (mQTLs) from the blood were performed using SMR methods to prioritize putative blood OS genes and their regulatory elements associated with CD risk. Up-to-date intestinal eQTLs and fecal microbial QTLs (mbQTLs) were integrated to uncover potential interactions between host OS gene expression and gut microbiota through SMR and colocalization analysis. Two additional Mendelian randomization (MR) methods were used as sensitivity analyses. Putative results were validated in an independent multi-omics cohort from the First Affiliated Hospital of Sun Yat-sen University (FAH-SYS). Results: A meta-analysis from six datasets identified 438 OS-related DEGs enriched in intestinal enterocytes in CD from 817 OS-related genes. Five genes from blood tissue were prioritized as candidate CD-causal genes using three-step SMR methods: BAD, SHC1, STAT3, MUC1, and GPX3. Furthermore, SMR analysis also identified five putative intestinal genes, three of which were involved in gene–microbiota interactions through colocalization analysis: MUC1, CD40, and PRKAB1. Validation results showed that 88.79% of DEGs were replicated in the FAH-SYS cohort. Associations between pairs of MUC1–Bacillus aciditolerans and PRKAB1–Escherichia coli in the FAH-SYS cohort were consistent with eQTL–mbQTL colocalization. Conclusions: This multi-omics integration study highlighted that OS genes causal to CD are regulated by DNA methylation and host-microbiota interactions. This provides evidence for future targeted functional research aimed at developing suitable therapeutic interventions and disease prevention. [ABSTRACT FROM AUTHOR]

Qishiwei Zhenzhu pills are one of the most representative precious treasure proprietary medicines and have been used for nearly 500 years in clinical practice in Chinese. This medicine can prevent diseases and play a certain role in fighting altitude sickness with cerebral ischemia. This study used LC-MS to analyse the chemical constituents of Qishiwei Zhenzhu pills, which laid a foundation for the improvement of the quality standard and the basic research of pharmacodynamics substances. This study aims to reveal the mechanism of Qishiwei Zhenzhu pills on cerebral ischemia from the perspective of the inflammatory and apoptotic pathway. UPLC-Q-TOF-MS was used to analyse the chemical constituents of Qishiwei Zhenzhu pills qualitatively. HPLC-QQQ-MS was used to analyse the contents of Qishiwei Zhenzhu pills quantitatively. The therapeutic target and pathway of Qishiwei Zhenzhu pills in the treatment of ischemic stroke were predicted on the basis of network pharmacology. On the basis of the MCAO rat model, the cerebral infarction rate (TTC staining) and the number of Nissl bodies (toluidine blue staining) were measured, the pathological morphologies of cortex and hippocampus were observed (HE staining), and the mRNA levels were determined by RT-PCR. The protein expressions of Bax, Bcl-2, and Caspase3 in the ischemic brain tissue of rats were determined using the WB method. A total of 42 chemical constituents, including 11 triterpenoids, 10 flavonoids, 8 organic acids and their derivatives, 4 diterpenoids, 4 tannins, 2 steroids, and 3 other components, were identified from Qishiwei Zhenzhu pills by UPLC-Q-TOF-MS. HPLC-QQQ-MS results found that among the 16 different batches, the content difference between the two batches of preparations with the national drug approval number was small and that the quality was stable. However, significant differences were observed among the preparations of nine medical institutions. Network pharmacology study found that the effect of Qishiwei Zhenzhu pills might be related to the AGE-rage and tumour necrosis factor signalling pathways. Qishiwei Zhenzhu pills could improve the neurobehavioral abnormalities of MCAO rats, reduce the rate of cerebral infarction, improve the pathological changes in the hippocampal area of brain tissue, and increase the number of Nissl body in the brain tissue. Qishiwei Zhenzhu pills tended to reduce the mRNA transcription levels of Bax, Caspase-3, p65, c-fos and VEGF-A and increase the expression of Bcl-2 and MAPK8 mRNA. Moreover, the Bax protein expression tended to decrease, and the bcl-2 protein expression tended to increase. A total of 42 chemical components were qualitatively identified from Qishiwei Zhenzhu pills, and 16 chemical components from 16 batches were determined. These components improved the quality standard level of Qishiwei Zhenzhu pills and provided reference for the later exploration of its pharmacodynamics substance basis. The protective mechanism of Qishiwei Zhenzhu pills against ischemic stroke might be related to the downregulation of the apoptosis factor caspase-3. [Display omitted] • The 42 chemical constituents in Qishiwei Zhenzhu pills were identified qualitatively by UPLC-Q-TOF-MS. • HPLC-QQQ-MS was used to quantitatively analyse 16 chemical components in Qishiwei Zhenzhu pills. • Through the exploration of network pharmacology, the potential molecular mechanism of this study was predicted. • Qishiwei Zhenzhu pills can reduce the expression level of caspase-3 protein, which is related to the apoptosis pathway. [ABSTRACT FROM AUTHOR]

Context:Rhizoma coptidisis a broadly used traditional Chinese medicine (TCM). The investigation of the influence of species and geographical origins on the phytochemicals ofR. coptidisis crucial for its reasonable application and quality control. Objective:Development of an effective method to systematically study the phytochemical variations of the rhizomes of threeCoptisspecies (Ranunculaceae) (Coptis chinensisFranch,Coptis deltoideaC.Y. Cheng et Hsiao andCoptis teetaWall.) and a species (i.e.,C. chinensis) obtained from bothDaodiand non-Daodiproduction regions. Results:The three species had significant differences in their phytochemicals. The rhizome ofC. chinensiscontained more epiberberine (13.52 ± 2.65 mg/g), palmatine (18.20 ± 2.89 mg/g), coptisine (23.32 ± 4.27 mg/g) and columbamine (4.89 ± 1.16 mg/g), whereas the rhizomes ofC. deltoideaandC. teetashowed the highest level of jatrorrhizine (8.52 ± 1.36 mg/g) and berberine (81.06 ± 4.83 mg/g), respectively. Moreover, the rhizome ofC. chinensisfrom threeDaodiproduction regions (Shizhu, Lichuan and Emeishan) contained more alkaloids than those from three non-Daodiproduction regions (Mianyang, Shifang and Zhenping). Discussion and conclusion:It is necessary to use the threeR. coptidisspecies differentially in TCM clinical practice.Daodi C. chinensismedicinal materials have better quality than most non-Daodiones, and so they should be preferred for TCM prescription. The combination of HPLC-based fingerprint analysis and quantification of multi-ingredients with statistical analysis provided an effective approach for species discrimination and quality evaluation ofR. coptidis. [ABSTRACT FROM AUTHOR]

This work obtained and identified pterocephanoside A (1), one new iridoid glucoside derivative with rare structure of three iridoid glycosides linked to cyclopenta[c]pyran-3(1H)-one, and 10 known iridoids (2–11) from Pterocephalus hookeri through silica gel column chromatography and semi-preparative HPLC. The structure of the new compound was confirmed by 1D and 2D NMR and HRMS data analysis. Compounds 1 and 2 were isolated from this plant for the first time. The iridoids mostly possessed seco-iridoid subtype and iridoid subtype skeletons from P. hookeri. Compounds 1, 3, 4, and 6–11 showed weak anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

Group 3 innate lymphoid cells (ILC3s) regulate inflammation and tissue repair at mucosal sites, but whether these functions pertain to other tissues—like the kidneys—remains unclear. Here, we observed that renal fibrosis in humans was associated with increased ILC3s in the kidneys and blood. In mice, we showed that CXCR6+ ILC3s rapidly migrated from the intestinal mucosa and accumulated in the kidney via CXCL16 released from the injured tubules. Within the fibrotic kidney, ILC3s increased the expression of programmed cell death-1 (PD-1) and subsequent IL-17A production to directly activate myofibroblasts and fibrotic niche formation. ILC3 expression of PD-1 inhibited IL-23R endocytosis and consequently amplified the JAK2/STAT3/RORγt/IL-17A pathway that was essential for the pro-fibrogenic effect of ILC3s. Thus, we reveal a hitherto unrecognized migration pathway of ILC3s from the intestine to the kidney and the PD-1-dependent function of ILC3s in promoting renal fibrosis. [Display omitted] • ILC3s migrate from the gut to the injured kidney via the CXCR6-CXCL16 axis • ILC3s trigger renal fibrosis through PD-1-dependent IL-17A production • PD-1 inhibits IL-23R endocytosis on ILC3 to amplify JAK2/STAT3/RORγt/IL-17A pathway Infiltrating immune cells are important contributors to tissue fibrosis. Here, Liang et al. reveal that intestinal ILC3s migrate to the kidney via CXCR6/CXCL16 during renal fibrosis. Within the kidney, immigrated ILC3s express PD-1, which regulates IL-23 receptor endocytosis and enhances IL-17A production, thus exacerbating the fibrotic niche. [ABSTRACT FROM AUTHOR]

Gallic acid (GA), also known as 3,4,5-trihydroxybenzoic acid, is a natural secondary metabolite and widely isolated from various fruits, plants and nuts. In recent years, GA has received increasing attention for its powerful anti-inflammatory properties. The purpose of this review is to clearly illuminate the pharmacological activities and related molecular mechanisms of GA in inflammatory diseases. After consulting a large number of literatures, we made a comprehensive exposition on the chemical characteristics, plant origins, pharmacokinetics and toxicity of GA, especially its pharmacological activities and mechanisms of action. Although the plant source of GA is very rich, its lower extraction rate limits the application of GA in development. It is worth mentioning that GA can not only be separated from many plants, but also be produced in large quantities through biological and chemical synthesis. According to pharmacokinetic studies, the absorption and elimination of GA after oral administration are fast, while the structural optimization or dosage form adjustment of GA is beneficial to increase its bioavailability. Promisingly, toxicity studies have shown that GA scarcely has obvious toxicity or side effects in a variety of animal experiments and clinical trials. The results show that the anti-inflammatory mechanisms of GA mainly involved MAPK and NF-κB signaling pathways. It thus weakens the inflammatory response by reducing the release of inflammatory cytokines, chemokines, adhesion molecule and cell infiltration. Due to its excellent pharmacological activities, GA is expected to be a potential candidate for the treatment of various inflammation-related diseases. This paper will provide theoretical basis for the clinical application of GA and guide the future research and medicinal development of GA. [ABSTRACT FROM AUTHOR]

Adhatoda vasica Nees (AVN) is commonly used to treat joint diseases such as rheumatoid arthritis (RA) in ethnic minority areas of China, especially in Tibetan and Dai areas, and its molecular mechanisms on RA still remain unclear. Network pharmacology, a novel strategy, utilizes bioinformatics to predict and evaluate drug targets and interactions in disease. Here, network pharmacology was used to investigate the mechanism by which AVN acts in RA. The chemical compositions and functional targets of AVN were retrieved using the systematic pharmacological analysis platform PharmMapper. The targets of RA were queried through the DrugBank database. The protein-protein interaction network (PPI), Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of key targets were constructed in the STRING database, and the network visualization analysis was performed in Cytoscape. Maestro 11.1, a type of professional software, was used for verifying prediction and analysis based on network pharmacology. By comparing the predicted target information with the targets of RA-related drugs, 25 potential targets may be related to the treatment of RA, among which MAPK1, TNF, DHODH, IL2, PTGS2, and JAK2 may be the main potential targets for the treatment of RA. Finally, the chemical components and potential target proteins were scored by molecular docking, and compared with the ligands of the protein, the prediction results of network pharmacology were preliminarily verified. The active ingredients and mechanism of AVN against RA were firstly investigated using network pharmacology. Additionally, this research provided a solid foundation for further experimental studies. [ABSTRACT FROM AUTHOR]

[Display omitted] • Spatial metabolomics reveal microregions of Panax quinquefolius roots. • Combining UPLC-Q-TOF/MS and DESI-MSI for metabolomics research. • Different chemical components showed different distributions in P. quinquefolius. • Unknown chemical composition could be visualized by DESI-MSI. Panax quinquefolius is a natural homology medicine and food that is rich in bioactive ingredients, such as ginsenosides and polysaccharides. The combination of ultra-performance liquid chromatography quadrupole/time of flight-mass spectrometry (UPLC-Q-TOF/MS) and desorption electrospray ionization mass spectrometry imaging (DESI-MSI) was used for the first time in a spatial metabolomics analysis to comprehensively evaluate the differential components in different microregions of P. quinquefolius. UPLC-Q-TOF/MS and DESI-MSI combined with principal component analysis and orthogonal partial least squares-discriminant analysis were used to screen differential metabolites. UPLC-Q-TOF/MS and DESI-MSI screened 27 and 23 differential metabolites, respectively, among which 15 differential metabolites were identified by both methods. It was found that some components, such as ginsenoside Rg1 and malonyl-ginsenoside Rc, were mainly distributed in P of the transverse slice of P. quinquefolius roots, while ginsenoside Ro and malonyl-ginsenoside Rd were mainly distributed in C. The methods and results of this study could be used to understand the precise localization, biosynthesis, and biological functions of special metabolites in P. quinquefolius. [ABSTRACT FROM AUTHOR]

Ulcerative colitis (UC) is an inflammatory disease of the colon. IL1R2 , which encodes IL-1 receptor type 2 (IL-1R2), was reported as a risk gene for UC. To elucidate the roles of IL-1R2 in the development of colitis, we examined the development of dextran sodium sulfate-induced colitis, a mouse model for UC using Il1r2 −/− mice. We found the severity score of colitis was milder in Il1r2 −/− mice compared with wild-type (WT) mice when they were housed separately, however the severity score was similar when they were housed in a cage. In the separate housing condition, relative contents of Actinobacteria and Bacilli in feces of Il1r2 −/− mice were lower than that of WT mice. Furthermore, IL-1β induced the expression of antimicrobial peptides (AMPs) from colon. Thus, we show that IL-1R2 is harmful for the development of colitis, because IL-1R2 promotes the growth of proinflammatory intestinal microbiota by suppressing IL-1β-induced AMP production. [ABSTRACT FROM AUTHOR]

Context:Pterocephalus hookeri(C. B. Clarke) Hock., a traditional Tibetan herbal medicine rich in glycosides, has been used to treat several diseases including rheumatoid arthritis. Objective:To evaluate the anti-arthritic activity of total glycosides fromP. hookeri, and its possible mechanisms of action. Materials and methods:Anti-arthritic activity of total glycosides fromP. hookeri(oral administration for 30 days at 14–56 mg/kg) was evaluated using paw swelling, arthritis scores and histopathological measurement in adjuvant-induced arthritis (AA) Sprague-Dawley rats. The NF-κB p65 expression in synovial tissues, and serum superoxide dismutase (SOD) activity, malondialdehyde (MDA) and nitric oxide (NO) levels was measured in AA rats, respectively. Further assessment of anti-inflammatory and analgesic activities of these glycosides were carried out using inflammation and hyperalgesia models induced by xylene, carrageenan, agar and acetic acid, respectively. Results:Total glycosides (56 mg/kg) decreased the paw swelling (38.0%,p < 0.01), arthritis scores (25.3%,p < 0.01) and synovial inflammation in AA rats. The glycosides significantly (p < 0.05–0.01) attenuated the inflammation induced by xylene, carrageenan, acetic acid and agar, increased the pain threshold in acetic acid-induced writhing in mice and mechanical stimuli-induced hyperalgia in AA rats. The glycosides (14, 28, 56 mg/kg) also suppressed the NF-κB p65 expression (33.1–78.2%,p < 0.05–0.01), reduced MDA (21.3–35.9%,p < 0.01) and NO (20.3–32.4%,p < 0.05–0.01) levels, respectively, enhanced the SOD activity (7.8%,p < 0.05) at 56 mg/kg in AA rats. Discussion and conclusion:Our findings confirmed the anti-arthritic property of the total glycosides fromP. hookeri, which may be attributed to its inhibition on NF-κB signalling and oxidative stress. [ABSTRACT FROM AUTHOR]

In this study, we characterized the distribution of microsatellites in the genomes and genes of Centruroides exilicauda and Mesobuthus martensii , carried out Gene Ontology (GO) analysis and GO enrichment analysis of coding sequences (CDSs) with microsatellite (SSR). In addition, over-represented GO functions related to environmental interactions, development process and methylation were identified to develop functional markers and facilitate further analysis of microsatellite function in the genes of scorpions. Location analysis indicated that microsatellites were predominantly concentrated at both ends of genes. Most genes containing microsatellite had the SSR present at only one locus, from which we infer that the number of SSRs per gene is limited even though intragenic tandem repeats can generate functional variability. Lastly, we identified 75 SSRs in 64 genes of 54 expanded gene families and 1 SSR in the toxin gene of Mesobuthus martensii , allowing future studies on the effect of microsatellites on gene function. [ABSTRACT FROM AUTHOR]

Trueperella pyogenes is a commensal and opportunistic pathogen normally causes mastitis, liver abscesses and pneumonia of economically important livestock. To date, no specific control measure was reported to prevent T. pyogenes infections. In this study, we first constructed a recombinant plasmid pVAX1-PLO based on the main virulent factor pyolysin gene as DNA vaccine against T. pyogenes infection. Subsequently, transient expression of pVAX1-PLO and pcDNA3.1/V5-fIL-1β were identified in Human embryonic kidney cells (HEK293T) by immunofluorescence assay. Humoral and cellular immune responses were evaluated in mice to compare the immunogenicity between different immunized groups. The results showed that the successful expression of PLO or fIL-1β protein was detected by confocal microscopy for cells transfected with plasmid pVAX1-PLO and/or pcDNA3.1/V5-fIL-1β. The mice immunized with pVAX1-PLO elicited a higher titer of PLO-specific antibody than the control group. The levels of IFN-γ and IL-2 were significantly increased in the pVAX1-PLO immunized mice, while the expression level of IL-4 was slightly increased but not significant. These findings suggested that the DNA vaccine pVAX1-PLO can primarily induce Th1 immune response. The residual Colony-Forming Units (CFUs) from the liver and peritoneal fluid were decreased obviously in the pVAX1-PLO treated mice compared with the control. Importantly, co-immunization with pcDNA3.1/V5-fIL-1β and pVAX1-PLO could enhance host humoral and cellular immune responses and significantly protect mouse from T. pyogenes infection. In conclusion, our study provides a promising strategy against T. pyogenes infections and implies the potential clinical application of combined DNA vaccines in diseases control. [ABSTRACT FROM AUTHOR]

Composed of dried Aconitum pendulum and Aconitum flavum roots, Tiebangchui, is an important Tibetan medicine and has been traditionally and widely used as a remedy for cold and pain for thousands of years because of its extraordinary pharmacological activities. The toxicity and efficacy of Tiebangchui as a typical toxic traditional Tibetan medicine, are interdependent, and thus to make sure its safe use in clinics is also noteworthy. This review aims to document and summarize critical and comprehensive information about traditional uses, phytochemistry, pharmacology, toxicology and processing methods of Tiebangchui. Perspectives for possible future investigations have been discussed. Relevant information about Tiebangchui (A. pendul um and A. flavum) was collected from internationally recognized electronic scientific databases, such as Web of Science, PubMed, Science Direct, Springer Link, ACS, and CNKI. Then, classic Tibetan medical books, such as Four Medical Tantra , and Jing Zhu Materia Medica , and official drug standards were reviewed. A total of 95 chemical constituents have been isolated and identified from Tiebangchui, and most of them were diterpenoid alkaloids. These phytochemicals showed a wide range of pharmacological properties, such as anti-inflammation, anti-rheumatoid arthritis, analgesic, local anesthetic, anti-cancer and anti-bacterial activities. Hence, Tiebangchui is broadly used in hundreds of preparations to treat fever, arthritis, rheumatic arthralgia, traumatic injury, furuncle and swelling. Cardiotoxicity, neurotoxicity and gastrointestinal toxicity are the main toxic effects caused by the Aconitum alkaloids of Tiebangchui. Various processing methods, including steaming, decocting and sand-frying, and traditional Tibetan medicine processing methods, such as processing with Hezi decoction, Qingke wine and Zanba, are effective in attenuating toxicity while retaining efficacy. The present review provides primary information of Tiebangchui, particularly for its traditional uses, botanical characteristics, phytochemicals, outstanding bioactivities and processing methods. However, studies that explored the in vivo pharmacokinetics and mechanism of Tiebangchui, as well as its quality markers, qualitative and quantitative analysis are still insufficient. Processing methods that attenuate toxicities, evaluations of efficacy, in vivo processes and biological effects, the mechanisms of processed products should be further explored. [Display omitted] [ABSTRACT FROM AUTHOR]

Cantleyoside (CA) is a kind of iridoid glycosides in Pterocephalus hookeri (C. B. Clarke) Höeck. The purpose of this study was to investigate the effects of CA on human rheumatoid arthritis fibroblast synovial cells (HFLS-RA). Cell proliferation of HFLS-RA was assessed by CCK-8. ELISA was used to detect cytokines NO, TNF-α, IL-1β/6, MCP-1, MMP-1/3/9 and metabolism-related ATPase activities and ATP levels. JC-1, DCFH-DA, Fluo-3 AM and Calcein AM probes were used to detect mitochondrial membrane potential (MMP), reactive oxygen species (ROS), Ca2+ and mitochondrial permeability conversion pore (MPTP), respectively. Isolated mitochondria assay was used to detect mitochondrial swelling. Oxygen consumption rate (OCR), extracellular acidification rate (ECAR) and real-time ATP production were measured using a Seahorse analyzer. Apoptosis was detected by TUNEL and Hoechst staining. Western blot was used to detect the expressions of AMPK/p-AMPK, Sirt 1, IκBα, NF-κB p65/p-NF-κB p65, Bcl-2 and Bax. Cytoplasmic nuclear isolation was also performed to detect the translocation of NF-κB. CA significantly suppressed cell proliferation and the levels of NO, TNF-α, IL-1β/6, MCP-1 and MMP-1/3/9 in HFLS-RA. In addition, CA promoted the apoptosis of HFLS-RA by increasing TUNEL and Hoechst positive cells and the ratio of Bax/Bcl-2. Inhibition of energy metabolism in HFLS-RA by CA reduced OCR, ECAR and real-time ATP generation rate. Importantly, CA promoted p-AMPK and Sirt 1 expression, inhibited IκBα degradation to reduce p-NF-κB and translocation. The results suggest that CA activates the AMPK/Sirt 1/NF-κB pathway by promoting mitochondrial dysfunction, thereby exerting anti-inflammatory and pro-apoptotic effects. [Display omitted] • CA could inhibit inflammatory responses by weakening the expression of inflammatory cytokines, chemokines and MMPs. • CA could induce mitochondrial dysfunction by overloading intracellular ROS and Ca2+ in HFLS-RA. • CA could reduce mitochondrial energy metabolism by restraining OCR, ECAR and real-time ATP production rates in HFLS-RA. • CA could promote apoptosis of HFLS-RA by the activation of AMPK/Sirt 1/NF-κB pathway. [ABSTRACT FROM AUTHOR]

Abstract: Rhizoma coptidis, a broadly used traditional Chinese medicine, derives from the dried rhizomes of Coptis chinensis Franch, Coptis deltoidea C.Y. Cheng et Hsiao and Coptis teeta Wall. Quantitative determination of protoberberine alkaloids in R. coptidis is critical for controlling its quality. In this study, a rapid, simple and accurate quantitative 1H NMR (qNMR) method was developed for simultaneous determination of berberine, jatrorrhizine, epiberberine, coptisine, palmatine and columbamine in R. coptidis from the three species. Method validation was performed in terms of selectivity, precision, repeatability, stability, accuracy, robustness and linearity. The average recoveries obtained were in the range of 96.9–102.4% for all the six alkaloids. In addition, the qNMR data were analyzed with analysis of variance (ANOVA), hierarchical clustering analysis (HCA) and principal component analysis (PCA), and the results showed that the contents of the active alkaloids have significant difference among the three species. Compared with the conventional HPLC approach, the proposed qNMR method was demonstrated to be a powerful tool for quantifying the six alkaloids due to its unique advantages of high robustness, rapid analysis time and no need of standard compounds for calibration curves preparation. These findings indicate that this method has potential as a reliable method for quality evaluation of herb medicines, especially for protoberberine alkaloid-containing ones. [Copyright &y& Elsevier]

Summary: Epithelial keratinocyte proliferation is an essential element of wound repair, and abnormal epithelial proliferation is an intrinsic element in the skin disorder psoriasis. The factors that trigger epithelial proliferation in these inflammatory processes are incompletely understood. Here we have shown that regenerating islet-derived protein 3-alpha (REG3A) is highly expressed in keratinocytes during psoriasis and wound repair and in imiquimod-induced psoriatic skin lesions. The expression of REG3A by keratinocytes is induced by interleukin-17 (IL-17) via activation of keratinocyte-encoded IL-17 receptor A (IL-17RA) and feeds back on keratinocytes to inhibit terminal differentiation and increase cell proliferation by binding to exostosin-like 3 (EXTL3) followed by activation of phosphatidylinositol 3 kinase (PI3K) and the kinase AKT. These findings reveal that REG3A, a secreted intestinal antimicrobial protein, can promote skin keratinocyte proliferation and can be induced by IL-17. This observation suggests that REG3A may mediate the epidermal hyperproliferation observed in normal wound repair and in psoriasis. [ABSTRACT FROM AUTHOR]

Angelica anomala Avé-Lall (Chuanbaizhi in Chinese) is an important medicinal plant which can be used in traditional Chinese medicines; however, there are no authentic and universal methods to differentiate this Sichuan famous-region drug of A. anomala from a large number of non-famous-region and false drugs. It has been demonstrated that DNA barcoding is a molecular diagnostic method for species identification, which uses a single standardized DNA fragment. In this study, we tested five DNA barcoding candidates ( matK, ITS, ITS2, rbcL, and psbA-trnH), and we found that ITS was the best candidate to authenticate the famous-region drug of A. anomala. Moreover, through comparative analysis of these five DNA barcodes between A. anomala and Angelica dahurica, we found that ITS had the most and ITS2 had more variable regions, but the psbA-trnH, rbcL, and matK regions were identical. Hence, we suggest ITS as the DNA barcoding to identify A. anomala and A. dahurica. Moreover, we are determined to adopt the A. anomala as the accurate Latin name of Chuanbaizhi. [ABSTRACT FROM AUTHOR]