Analysis of Enrichment Pathway, Hub Gene, and Protein-Protein Interaction Network in Rheumatoid Arthritis and Construction of Molecular Subtypes in Peripheral Blood.

Objective: To analyze the enrichment pathway, hub gene, and Protein-protein interaction (PPI) network of rheumatoid arthritis (RA) and construct peripheral blood subtypes based on integrated bioinformatics analysis. Methods: Suitable datasets were screened from the GEO database based on titles and abstracts, batch positive analysis was performed using R language, and KEGG enrichment analysis and GO enrichment analysis were performed. After screening the differential genes, the PPI network was constructed, and the hubba plug-in of Cytoscape software was used to obtain the top 10 hub genes(key regulatory genes). hub genes were used as the typing condition to identify the molecular subtypes of synovial tissue and peripheral blood of arthritis. Results: GSE12021 and GSE93272 have been chosen for analysis. GSE12021 presents the transcriptome analysis of human joint synovial tissue, comprising 12 samples from patients with rheumatoid arthritis and 9 samples from normal healthy individuals. On the other hand, GSE93272 includes human peripheral blood samples, comprising 232 samples from patients with rheumatoid arthritis and 43 samples from normal healthy individuals. The main results of GSE12021 KEGG enrichment were Parathyroid hormone synthesis, Relaxin signaling pathway, TNF signaling pathway, Rheumatoid arthritis, T cell receptor signaling pathway, Th1 and Th2 cell differentiation, Th17 cell differentiation, Toll-like receptor signaling pathway and so on. The main results of GSE12021 GO enrichment were regulation of feeding behavior, regulation of neuron death, positive regulation of cell-cell adhesion, and positive regulation of leukocyte activation. The top 10 hub genes were CD8A, JUN, CTLA4, CD19, LCK, FOS, CCL5, IL7R, CCR7 and CD247. Synovial tissue and peripheral blood subtypes of rheumatoid arthritis showed that the two classification methods maintained consistency. Conclusion: Identifying the Hub gene in peripheral blood helps screen molecular subtypes of rheumatoid arthritis.

Assembly and comparative analysis of the first complete mitochondrial genome of a traditional Chinese medicine Angelica biserrata (Shan et Yuan) Yuan et Shan.

Duhuo, a member of the Angelica family, is widely used to treat ailments such as rheumatic pain. It possesses a diverse array of bioactivities, including anti-tumor, anti-inflammatory, and analgesic properties, as recent pharmacological research has revealed. Nevertheless, the mtDNA of Angelica species remains relatively unexplored. To address this gap, we sequenced and assembled the mtDNA of A. biserrata to shed light on its genetic mechanisms and evolutionary pathways. Our investigation indicated a distinctive multi-branched conformation in the A. biserrata mtDNA. A comprehensive analysis of protein-coding sequences (PCGs) across six closely related species revealed the presence of 11 shared genes in their mitochondrial genomes. Intriguingly, positive selection emerged as a significant factor in the evolution of the atp4, matR, nad3, and nad7 genes. In addition, our data highlighted a recurring trend of homologous fragment migration between chloroplast and mitochondrial organelles. We identified 13 homologous fragments spanning both chloroplast and mitochondrial genomes. The phylogenetic tree established a close relationship between A. biserrata and Saposhnikovia divaricata. To sum up, our research would contribute to the application of population genetics and evolutionary studies in the genus Acanthopanax and other genera in the Araliaceae family.

Inducing tumor ferroptosis via a pH-responsive NIR-II photothermal agent initiating lysosomal dysfunction.

Ferroptosis is a unique programmed cell death process that was discovered a few years ago and plays an important role in tumor biology and treatment. However, it still remains a challenge to modulate tumor ferroptosis by spatiotemporally controlled cell-intrinsic Fenton chemistry. Herein, a pH activated photothermal sensitizer IR-PE has been designed and synthesized on the basis of cyanine bearing a diamine moiety, which is capable of triggering the lysosomal dysfunction-mediated Fenton pathway under the irradiation of near-infrared light to evoke ferroptosis, thereby improving antitumor efficacy and mitigating systemic side effects.

Differences in Carbon Sequestration Ability of Diverse Tartary Buckwheat Genotypes in Barren Soil Caused by Microbial Action.

Planting plants to increase soil carbon input has been widely used to achieve carbon neutrality goals. Tartary buckwheat not only has good barren tolerance but is also rich in nutrients and very suitable for planting in barren areas. However, the effects of different genotypes of Tartary buckwheat roots and rhizosphere microorganisms on soil carbon input are still unclear. In this study, ozone sterilization was used to distinguish the sources of soil organic acids and C-transforming enzymes, and the contribution of root and rhizosphere microorganisms to soil carbon storage during the growth period of two genotypes of tartary buckwheat was studied separately to screen suitable varieties. Through the analysis of the experimental results, the conclusions are as follows: (1) The roots of Diqing tartary buckwheat have stronger carbon sequestration ability in a barren environment than Heifeng, and the microorganisms in Diqing tartary buckwheat soil will also increase soil carbon input. Therefore, Diqing tartary buckwheat is more suitable for carbon sequestration than Heifeng tartary buckwheat in barren soil areas. (2) In the absence of microorganisms, the rhizosphere soil of tartary buckwheat can regulate the storage of soil organic carbon by secreting extracellular enzymes and organic acids. (3) The structural equation model showed that to promote carbon sequestration, Heifeng tartary buckwheat needed to inhibit microbial action when planted in the barren area of Loess Plateau, while Diqing tartary buckwheat needed to use microbial-promoting agents. Adaptive strategies should focus more on cultivar selection to retain carbon in soil and to assure the tolerance of fineness in the future.

Systemic Colonization of Potato Plants by Verticillium dahliae Leads to Infection of Tubers and Sprouting Buds.

A green fluorescent protein (GFP)-tagged isolate of Verticillium dahliae was used to study its colonization in potato plants and tubers. Three-week-old potato plants of the highly susceptible cultivar 'Shepody' were inoculated with a conidial suspension of a GFP-tagged isolate of V. dahliae using a wound inoculation method. Colonization was studied using confocal microscopy combined with tissue sections. Conidia germinated and hyphae grew along the root hairs, elongation zones, and root caps between 24 and 96 h postinoculation (HPI). At 7 days postinoculation (DPI), the pathogen advanced to cortical tissues and grew into the root vascular bundles. At 8 weeks postinoculation (WPI), the stem epidermal cells, cortical tissues, vascular elements, and petioles were fully colonized by the mycelium of V. dahliae. At 11 WPI, the pathogen was detected in the stolon and progeny tubers, as confirmed by both GFP signals in tissues and reisolation of the pathogen on the semiselective NP-10 medium. Progeny potato tubers were harvested from the inoculated potato plants, and the GFP-signal was observed in the epidermal cells and vascular elements of sprouting buds that emerged from the harvested tubers. The infection rate of progeny tubers detected on semiselective NP-10 medium ranged from 34.55 to 55.56%, with an average of 45.31%. In conclusion, we report, for the first time, the entire progression of colonization by V. dahliae in potato plant tissues, progeny tubers, as well as of the sprouting buds that emerged from progeny tubers.

Exploring the Antiovarian Cancer Mechanisms of Salvia Miltiorrhiza Bunge by Network Pharmacological Analysis and Molecular Docking.

Background: Ovarian cancer was one of the gynecological malignant tumors. Salvia miltiorrhiza Bunge (SMB) was a kind of herbal medicine with an antitumor effect. However, the inhibitory effect of SMB on ovarian cancer and its potential mechanism were still unclear. Objective: The antitumor effect of SMB on ovarian cancer was studied by network pharmacology and molecular docking techniques, and its possible molecular mechanisms were analyzed. Method: The active ingredients of SMB and the target data of ovarian cancer were obtained from the Traditional Chinese Medicines for Systems Pharmacology Database (TCMSP) and the GeneCards database. The relationship between active ingredients of SMB and ovarian cancer targets was analyzed by String database, David 6.8 online database, and Cytoscape 3.7.2 software, and then potential pathways were screened out. In addition, molecular docking technology was used to verify further the binding effect of antiovarian cancer pathway targets with active ingredients of SMB. Finally, survival analysis was performed for all potential targets. Results: We analyzed 71 SMB-ovarian cancer common targets, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that the PI3K-Akt signaling pathway might be an essential pathway for SMB to inhibit ovarian cancer. Luteolin, Tanshinone IIA, and Cryptotanshinone in SMB might play an important role. HSP90AA1, CDK2, and PIK3CG might be potential targets of SMB in inhibiting ovarian cancer. Conclusion: Through network pharmacology and molecular docking analysis, we found that SMB might partially inhibit ovarian cancer by the PI3K-Akt signaling pathway. We believe that SMB might be a potential therapeutic agent for ovarian cancer patients.

The complete chloroplast genome sequence of Heracleum millefolium Diels (Apiaceae).

We assembled the complete chloroplast genome of Heracleum millefolium which is a traditional widely used medicinal plant in China. The whole genome is 150,025 bp in length which was divided into four subregions: a large single-copy region (93,645 bp), a pair of 19,458 bp inverted repeats regions, and a small single-copy region (17,464 bp), respectively. Additionally, the chloroplast genome of H. millefolium detected 128 genes, including 85 protein coding genes, 36 transfer RNAs, and eight ribosomal RNAs. The overall GC content of this chloroplast genome is 37.5% and the mean coverage value is 1752.4x. Phylogenetic analysis based on 17 chloroplast genomes dataset was conducted to clarify the relationships of the major clades in Apiaceae. The results strongly supported the monophyly of Heracleum and the closer relationship of H. millefolium and H. candicans.

Efficient Separation and Recovery of Petroleum Hydrocarbon from Oily Sludge by a Combination of Adsorption and Demulsification.

The treatment of oily sludge (OS) can not only effectively solve environmental pollution but also contribute to the efficient use of energy. In this study, the separation effect of OS was analyzed through sodium lignosulfonate (SL)-assisted sodium persulfate (S/D) treatment. The effects of SL concentration, pH, temperature, solid-liquid ratio, revolving speed, and time on SL adsorption solubilization were analyzed. The effects of sodium persulfate dosage, demulsification temperature, and demulsification time on sodium persulfate oxidative demulsification were analyzed. The oil removal efficiency was as high as 91.28%. The results showed that the sediment was uniformly and finely distributed in the S/D-treated OS. The contact angle of the sediment surface was 40°, and the initial apparent viscosity of the OS was 56 Pa·s. First, the saturated hydrocarbons and aromatic hydrocarbons on the sediment surface were adsorbed by the monolayer adsorption on SL. Stubborn, cohesive oil agglomerates were dissociated. Sulfate radical anion (SO4-·) with a high oxidation potential, was formed from sodium persulfate. The oxidation reaction occurred between SO4-· and polycyclic aromatic hydrocarbons. A good three-phase separation effect was attained. The oil recovery reached 89.65%. This provides theoretical support for the efficient clean separation of oily sludge.

[Effects of nitrogen addition on the contents and stoichiometric ratio of nitrogen and potassium in a meadow steppe of Hulunbuir, China]. / æ°®ç´ æ·»åŠ å¯¹å‘¼ä¼¦è´å°”è‰ç”¸è‰åŽŸæ¤ç‰©æ°®é’¾å ƒç´ å«é‡å’Œè®¡é‡æ¯”çš„å½±å“.

Potassium (K) is the second most abundant nutrient in plant leaves after nitrogen (N) and the most abundant cation in plant cells. It plays an important role in plant growth regulation, homeostasis maintenance, and stress response. Previous studies on the effects of N input on plant nutrient status mainly focus on N and phosphorus (P), but less on K and its stoichiometry. We examined the effects of N input and mowing on K content and N:K at both plant functional group and community levels. We analyzed the relative contribution of changes in functional groups and community composition to changes of community level nutrition status. The results showed that N input increased N content of each plant functional group and increased K content of rhizomatous grasses and legumes. Mowing reduced N content of rhizomatous grasses and bunchgrass, but did not affect K content and N:K of all functional groups. Nitrogen input significantly increased plant N and K contents at the community level, while mowing significantly increased plant N content. Both N input and mowing did not affect plant N:K at functional group and community levels. The contribution of nutritional changes in plant functional groups to the variation at the community level was greater than that of changes in community composition. For all the three examined nutritional traits, the contribution of nutrients at functional group level and that of community composition showed negative covariation. Our results indicated that plant N:K had high homeostasis in meadow steppe and that plants could regulate N and K balance, which was of great significance for maintaining N:K stoichiometry under the background of increasing N deposition.

Genome-wide screening and identification of nuclear Factor-Y family genes and exploration their function on regulating abiotic and biotic stress in potato (Solanum tuberosum L.).

The Nuclear Factor-Y (NF-Y) transcription factor (TF), which includes three distinct subunits (NF-YA, NF-YB and NF-YC), is known to manipulate various aspects of plant growth, development, and stress responses. Although the NF-Y gene family was well studied in many species, little is known about their functions in potato. In this study, a total of 37 potato NF-Y genes were identified, including 11 StNF-YAs, 20 StNF-YBs, and 6 StNF-YCs. The genetic features of these StNF-Y genes were investigated by comparing their evolutionary relationship, intron/exon organization and motif distribution pattern. Multiple alignments showed that all StNF-Y proteins possessed clearly conserved core regions that were flanked by non-conserved sequences. Gene duplication analysis indicated that nine StNF-Y genes were subjected to tandem duplication and eight StNF-Ys arose from segmental duplication events. Synteny analysis suggested that most StNF-Y genes (33 of 37) were orthologous to potato's close relative tomato (Solanum lycopersicum L.). Tissue-specific expression of the StNF-Y genes suggested their potential roles in controlling potato growth and development. The role of StNF-Ys in regulating potato responses to abiotic stress (ABA, drought and salinity) was also confirmed: twelve StNF-Y genes were up-regulated and another two were down-regulated under different abiotic treatments. In addition, genes responded differently to pathogen challenges, suggesting that StNF-Y genes may play distinct roles under certain biotic stress. In summary, insights into the evolution of NF-Y family members and their functions in potato development and stress responses are provided.

The complete chloroplast genome of Saussurea medusa maxim. (Asteraceae), an alpine Tibetan herb.

Saussurea medusa is an important traditional Tibetan medicinal plant in China. In this study, we assembled the complete chloroplast (cp) genome of S. medusa. The complete S. medusa chloroplast genome is a circular molecular structure of 152,257 bp in length with coding GC 37.93%, consisting of two inverted repeats (25,204 bp) separated by a large single-copy region (83,334 bp) and a small single-copy region (18,515 bp). The complete chloroplast genome of S. medusa contained 130 genes, including 87 protein-coding genes, 35 tRNA genes, and eight rRNA genes. Phylogenetic analysis shows that S. medusa is most closely related to Saussurea inversa and Saussurea pseudoleucoma. The complete chloroplast genome sequence of S. medusa facilitates the phylogenetic studies of Asteraceae.

[Systematic review and sequential analysis of Xuebijing Injection in treatment of systemic inflammatory response syndrome].

To systematically review the efficacy of Xuebijing Injection combined with western medicine in the treatment of systemic inflammatory response syndrome(SIRS). In this study, CBM, CNKI, Wanfang, VIP, PubMed and EMbase databases were retrieved for clinical randomized controlled trials on the effect of Xuebijing Injection combined with western medicine in the treatment of SIRS from the establishment of the database to July 31, 2020. After screening, Meta-analysis was conducted by RevMan 5.3 software, trial sequential analysis was conducted by TSA 0.9.5.10 beta software, and the evidence quality level was evaluated by GRADEprofiler 3.6.1 software. Meta-analysis showed that Xuebijing Injection combined with western medicine could reduce white blood cell count(MD=-2.32, 95%CI[-2.44,-2.21], P<0.000 01), C-reactive protein count(MD=-22.70, 95%CI[-29.61,-15.79], P<0.000 01), APACHE Ⅱ score(MD=-2.15, 95%CI[-2.43,-1.87], P<0.000 01), tumor necrosis factor alpha count(SMD=-1.23, 95%CI[-1.48,-0.99], P<0.000 01) and interleukin-6 count(SMD=-0.92, 95%CI[-1.15,-0.69], P<0.000 01), improve treatment efficiency(RR=1.39, 95%CI[1.23, 1.56], P<0.000 01), reduce incidence of multiple organ dysfunction(RR=0.47, 95%CI[0.35, 0.64], P<0.000 01) and mortality(RR=0.22, 95%CI[0.13, 0.37], P<0.000 01), which were better than western medicine treatment alone. Trial sequential analysis showed that in terms of reducing the incidence of multiple organ dysfunction and C-reactive protein count, the cumulative Z value passed through the traditional threshold, TSA threshold and expected information value, and reached the required number of cases. GRADE evaluation showed that the level of evidence was low or very low. According to the findings, Xuebijing Injection combined with western medicine is effective in treating SIRS. However, as the low quality of the included studies may affect the reliability of the conclusion, more high-quality studies shall be included for further verification in the future, so as to provide better suggestions for clinical medication.

Exploring the mechanisms of anti-ovarian cancer of Hedyotis diffusa Willd and Scutellaria barbata D. Don through focal adhesion pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Hedyotis diffusa Willd and Scutellaria barbata D.Don (HD-SB) pairing were widely used as traditional medicine known for their anti-tumor effects. However, the inhibitory effect of HD-SB on ovarian cancer and its potential mechanisms were still not clear. AIM OF THE STUDY: Our study identified the anti-tumor effect of HD-SB on ovarian cancer and analyzed the potential mechanisms by the network pharmacology and molecular docking method. MATERIALS AND METHODS: The inhibitory effect of HD-SB combination on the growth and migration of ovarian cancer was detected by MTT and transwell assays. The effective ingredients of HD-SB and their potential targets were obtained from the Traditional Chinese Medicines for Systems Pharmacology Database (TCMSP), the GeneCards database, and the UniProt database. The relationships between active ingredients of HD-SB and potential targets or pathways of ovarian cancer were analyzed by String database, Cytoscape 3.7.2 software, and David 6.7 online database. The anti-ovarian cancer targets of HD-SB in the focal adhesion pathway were identified by RT-qPCR and molecular docking. RESULTS: HD-SB combination significantly inhibited the proliferation and migration of ovarian cancer cells. We observed that the 1:2 ratio of HD-SB had the lowest IC50 value. 60 gene targets of 33 active ingredients in HD-SB were selected by pharmacokinetic parameters. The network pharmacological analysis showed that quercetin, luteolin, and baicalein might be the important anti-ovarian cancer ingredients in HD-SB, and the inhibitory effects of these three ingredients on the proliferation of ovarian cancer cells were verified respectively. Functional enrichment results suggested that HD-SB inhibited ovarian cancer growth and migration mainly through the focal adhesion pathway and the potential targets were EGFR, MAPK1, VEGFA, and PIK3CG. CONCLUSIONS: HD-SB pairing significantly inhibited the proliferation and migration of ovarian cancer. Using network pharmacological methods and validation experiments, we found that HD-SB might, at least partially, inhibit ovarian cancer through the focal adhesion pathway. We believed that the HD-SB combination could be a potential therapeutic drug for the treatment of ovarian cancer patients.

Pithohirolide, an antimicrobial tetradepsipeptide from a fungus Pithomyces chartarum.

Pithohirolide (1), a new depsipeptide, was isolated from an ascomycetous fungus Pithomyces chartarum TAMA 581. The planar structure of 1 was elucidated on the basis of NMR and MS analyses and the absolute configuration was determined by the advanced Marfey's analysis, chiral-phase HPLC analysis, and synthesis of degradation product. Compound 1 possesses a cyclic structure comprising (S)-2-hydroxy-3-phenylpropanoic acid, (S)-3-hydroxy-3-phenylpropanoic acid, (S)-2-hydroxyisovaleric acid, and N-methyl-L-alanine, connected via three ester and one amide linkages. Compound 1 exhibited antimicrobial activity against Staphylococcus aureus and Saccharomyces cerevisiae at MIC 3.1 µg ml-1.

TMKS8A, an antibacterial and cytotoxic chlorinated α-lapachone, from a sea slug-derived actinomycete of the genus Streptomyces.

TMKS8A (1), a new chlorinated α-lapachone derivative, along with five known related metabolites, A80915 C (2), SF2415B1 (3), chlorinated dihydroquinone 3 (4), SF2415B3 (5), and A80915 C (6), were identified from the culture extract of Streptomyces sp. TMKS8, which was isolated from a sea slug, Paromoionchis tumidus. The structure of 1 was determined by the analysis of NMR and MS spectral data, assisted by NMR chemical shift prediction using DFT-based calculation. The absolute configuration was determined to be R by comparison of experimental and calculated ECD spectra. Compound 1 displayed antimicrobial activity against Gram-positive bacteria with MIC values ranging from 6.25 to 12.5 µg ml-1 and cytotoxicity against murine leukemia P388 cells with IC50 9.8 µM.

StRac1 plays an important role in potato resistance against Phytophthora infestans via regulating H2O2 production.

ROP GTPases (Rho-related GTPases from plant), a unique subgroup of the Rho family in plants, is a group of key regulators of different signaling pathways controlling plant growth and development, cell polarity and differentiation, and plant response against biotic and abiotic stresses. The present study determined the potential regulatory mechanism of potato ROP GTPase (StRac1) against Phytophthora infestans (P. infestans) infection. Protein secondary structure analysis indicated that StRAC1 is a Rho GTPase. The expression level of StRac1 was variable in different tissues of potato, with the highest expression in young leaves of both Shepody and Hutou potato varieties. After challenging with P. infestans, the expression level of StRac1was higher in resistance varieties Zihuabai and Longshu 7 than in susceptible varieties Shepody and Desiree. StRAC1 fusion with GFP subcellularly localized at the plasma membrane (PM) in tobacco epidermal cells. The potato with transient or stable over-expression of CA-StRac1 (constitutively active form of StRac1)exhibited a dramatic enhancement of its resistance against P. infestans infections. The increased resistance level in transgenic potato was accompanied with elevated H2O2 levels. Importantly, silencing StRac1 via virus-induced gene silencing (VIGS) in potato resulted in higher susceptibility to P. infestans infection than in control plants. In summary, our data reveal that StRac1 regulates potato resistance against P. infestans via positively modulating the accumulation of H2O2.

Effects of Jianpi Yiqi method for chronic obstructive pulmonary disease: A protocol for systematic review and meta-analysis.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease with high morbidity and mortality worldwide. Jianpi Yiqi method (JYM) is a classical Chinese therapy in the treatment of COPD. However, there is no systematic review related to JYM for COPD. In this study, we aim to systematically examine the efficacy and safety for clinical use of JYM. METHODS AND ANALYSIS: We will conduct a comprehensive retrieval in the following electronic databases: PubMed, Embase, MEDLINE, Cochrane Library Central Register of Controlled Trials, China National Knowledge Infrastructure (CNKI) database, Wanfang Data Knowledge Service Platform, Chinese Scientific Journals Database (VIP), Chinese Biomedical Literature Service System (SinoMed), and other sources. Two trained reviewers will identify relevant studies, extract data information, and then assess the methodical quality by the Cochrane risk of bias assessment tool, independently. Then the meta-analyses will be conducted by using the RevMan 5.2. Based on the heterogeneity test, data integration is performed using a fixed effect model or a random effects model. A sensitivity analysis will be performed to evaluate the stability of the results. Then publication bias assessment will be conducted by funnel plot analysis and Egger test. Finally, the quality of evidence will be assessed by the GRADE system. RESULTS: The results of our research will be published in a peer-reviewed journal. CONCLUSION: The conclusion of our systematic review will provide evidence to judge whether JYM is an effective intervention for patients with COPD. OSF REGISTRATION NUMBER: 10.17605/OSF.IO/JKQYV.

Nanosized Alumina Particle and Proteasome Inhibitor Bortezomib Prevented inflammation and Osteolysis Induced by Titanium Particle via Autophagy and NF-κB Signaling.

Autophagy and NF-κB signaling are involving in the process of Particle Disease, which was caused by the particles released from friction interface of artificial joint, implant materials of particle reinforced composite, scaffolds for tissue engineering, or material for drug delivery. However, the biological interaction of different material particles and the mechanism of proteasome inhibitor, Bortezomib (BTZ), against Titanium (Ti) particle-induced Particle Disease remain unclear. In this study, we evaluated effect of nanosized Alumina (Al) particles and BTZ on reducing and treating the Ti particle-induced inflammatory reaction in MG-63 cells and mouse calvarial osteolysis model. We found that Al particles and BTZ could block apoptosis and NF- κB activation in osteoblasts in vitro and in a mouse model of calvarial resorption induced by Ti particles. We found that Al particles and BTZ attenuated the expression of inflammatory cytokines (IL-1ß, IL-6, TNF-α). And Al prevented the IL-1ß expression induced by Ti via attenuating the NF- κB activation ß-TRCP and reducing the expression of Casepase-3. Expressions of autophagy marker LC3 was activated in Ti group, and reduced by Al and/not BTZ. Furthermore, the expressions of OPG were also higher in these groups than the Ti treated group. Collectively, nanosized Al could prevent autophagy and reduce the apoptosis, inflammatory and osteolysis induced by Ti particles. Our data offered a basic data for implant design when it was inevitable to use Ti as biomaterials, considering the outstanding mechanical propertie of Ti. What's more, proteasome inhibitor BTZ could be a potential therapy for wear particle-induced inflammation and osteogenic activity via regulating the activity of NF- κB signaling pathway.

Wenxin Keli Regulates Mitochondrial Oxidative Stress and Homeostasis and Improves Atrial Remodeling in Diabetic Rats.

Mitochondrial dysfunction and oxidative stress play an important role in the pathogenesis of both atrial fibrillation (AF) and diabetes mellitus (DM). Wenxin Keli (WXKL), an antiarrhythmic traditional Chinese medicine, has been shown to prevent cardiac arrhythmias through modulation of cardiac ion channels. This study tested the hypothesis that WXKL can improve atrial remodeling in diabetic rats by restoring mitochondrial function. Primary atrial fibroblasts of neonatal SD rats were divided into four groups: control, hydrogen peroxide (H2O2), H2O2+WXKL 1 g/L, and H2O2+WXKL 3 g/L groups. Intracellular mitochondrial membrane potential (MMP), reactive oxygen species (ROS), and mitochondrial oxygen consumption were measured. SD male rats were randomly divided into three groups: control, DM, and DM+WXKL groups. Rats in the DM+WXKL group were treated with daily gavage of WXKL at 3 g/kg. After eight weeks, echocardiography, hemodynamic examination, histology, electrophysiology study, mitochondrial respiratory function, and western blots were assessed. H2O2 treatment led to increased ROS and decreased intracellular MMP and mitochondrial oxygen consumption in primary atrial fibroblasts. WXKL improved the above changes. DM rats showed increased atrial fibrosis, greater left atrial diameter, lower atrial conduction velocity, higher conduction heterogeneity, higher AF inducibility, and lower mitochondrial protein expression, and all these abnormal changes except for left atrial diameter were improved in the DM+WXKL group. WXKL improves atrial remodeling by regulating mitochondrial function and homeostasis and reducing mitochondrial ROS in diabetic rats.

Effects of ticagrelor pretreatment on electrophysiological properties of stellate ganglion neurons following myocardial infarction.

Higher sympathetic activity predisposes to malignant ventricular arrhythmias in the context of myocardial infarction (MI). This is, in part, mediated by the electrical activity of the stellate ganglion (SG). The aim of this study is to examine the effects of ticagrelor pretreatment on the electrophysiological properties of SG neurons following MI in rabbits. MI was induced by isoproterenol (ISO) of 150 mg kg-1 d-1 (twice at an interval of 24 hours). Ticagrelor pretreatment was administered at low- (10 mg kg-1 d-1) or high-dose (20 mg kg-1 d-1). Protein and RNA expression were determined by immunohistochemical analysis and real-time PCR, respectively. The activity of sodium channel current (INa), delayed rectifier potassium current (IKDR), M-type potassium current (IKM) as well as action potentials (APs) from SG neurons were measured by whole-cell patch-clamp. Intracellular calcium concentrations were measured by confocal microscopy. Compared with the control group, the MI group exhibited a greater amplitude of INa, IKDR and IKM, significantly altered activation and inactivation characteristics of INa, no significant alterations in protein or mRNA expression of sodium and M-type potassium channels, along with higher AP amplitude and frequency and intracellular calcium concentrations. Most of these abnormalities were prevented by pretreatment with low- or high-dose ticagrelor. Our data suggest that ticagrelor exerts cardioprotective effects, potentially through modulating the activity of different ion channels in SG neurons.