Methyl-Based Methanogenesis: an Ecological and Genomic Review.

Methyl-based methanogenesis is one of three broad categories of archaeal anaerobic methanogenesis, including both the methyl dismutation (methylotrophic) pathway and the methyl-reducing (also known as hydrogen-dependent methylotrophic) pathway. Methyl-based methanogenesis is increasingly recognized as an important source of methane in a variety of environments. Here, we provide an overview of methyl-based methanogenesis research, including the conditions under which methyl-based methanogenesis can be a dominant source of methane emissions, experimental methods for distinguishing different pathways of methane production, molecular details of the biochemical pathways involved, and the genes and organisms involved in these processes. We also identify the current gaps in knowledge and present a genomic and metagenomic survey of methyl-based methanogenesis genes, highlighting the diversity of methyl-based methanogens at multiple taxonomic levels and the widespread distribution of known methyl-based methanogenesis genes and families across different environments.

The IMG/M data management and analysis system v.7: content updates and new features.

The Integrated Microbial Genomes & Microbiomes system (IMG/M: https://img.jgi.doe.gov/m/) at the Department of Energy (DOE) Joint Genome Institute (JGI) continues to provide support for users to perform comparative analysis of isolate and single cell genomes, metagenomes, and metatranscriptomes. In addition to datasets produced by the JGI, IMG v.7 also includes datasets imported from public sources such as NCBI Genbank, SRA, and the DOE National Microbiome Data Collaborative (NMDC), or submitted by external users. In the past couple years, we have continued our effort to help the user community by improving the annotation pipeline, upgrading the contents with new reference database versions, and adding new analysis functionalities such as advanced scaffold search, Average Nucleotide Identity (ANI) for high-quality metagenome bins, new cassette search, improved gene neighborhood display, and improvements to metatranscriptome data display and analysis. We also extended the collaboration and integration efforts with other DOE-funded projects such as NMDC and DOE Biology Knowledgebase (KBase).

Expanding the genomic encyclopedia of Actinobacteria with 824 isolate reference genomes.

The phylum Actinobacteria includes important human pathogens like Mycobacterium tuberculosis and Corynebacterium diphtheriae and renowned producers of secondary metabolites of commercial interest, yet only a small part of its diversity is represented by sequenced genomes. Here, we present 824 actinobacterial isolate genomes in the context of a phylum-wide analysis of 6,700 genomes including public isolates and metagenome-assembled genomes (MAGs). We estimate that only 30%-50% of projected actinobacterial phylogenetic diversity possesses genomic representation via isolates and MAGs. A comparison of gene functions reveals novel determinants of host-microbe interaction as well as environment-specific adaptations such as potential antimicrobial peptides. We identify plasmids and prophages across isolates and uncover extensive prophage diversity structured mainly by host taxonomy. Analysis of >80,000 biosynthetic gene clusters reveals that horizontal gene transfer and gene loss shape secondary metabolite repertoire across taxa. Our observations illustrate the essential role of and need for high-quality isolate genome sequences.

MRGPRX2 mediates immediate-type pseudo-allergic reactions induced by iodine-containing iohexol.

BACKGROUND: Iohexol is a typical iodinated radiocontrast medium and widely used in clinical angiography. Hypersensitivity reactions induced by iohexol are common side effects known to increase the risk for patients. Iodine is the main functional group of iohexol, and it can induce delayed anaphylaxis. However, iohexol also induces immediate-type allergies, but the underlying mechanism is still not clear. MRGPRX2 is a key receptor present on mast cells, which mediates pseudo-allergic reactions induced by various drugs. METHODS: We aimed to verify the relationship between iohexol-induced anaphylactic reactions and MRGPRX2. MRGPRX2-mediated pseudo-allergic reactions induced by iohexol were investigated in vivo and in vitro using a mouse model of local and systemic anaphylaxis and mast cell degranulation assays, respectively. RESULTS: Iohexol caused pseudo-allergic reactions in wild-type (WT) mice by activating mast cells to release histamine and cytokines. However, it did not induce a similar phenomenon in KitW-sh/W-sh (MUT) mice. Iohexol stimulated intracellular calcium ion (Ca2+) influx in MRGPRX2-HEK293, MrgprB2-HEK293, and LAD2 cells but not in NC-HEK293 cells. After knockdown of MRGPRX2 expression in LAD2 cells, the degree of iohexol-induced degranulation was reduced. In addition, after structural modification of iohexol by removal of iodine, a reduction in iohexol-induced effects, such as local and systemic anaphylaxis in mice and degranulation of LAD2 cells, could be observed. Iohexol was shown to induce immediate-type pseudo-allergic reactions via MRGPRX2, which was dependent on the presence of iodine. CONCLUSIONS: Conclusively, inhibition of MRGPRX2-mediated mast cell degranulation and cytokine release is important to prevent iohexol-induced immediate-type pseudo-allergic reactions.

A genomic catalog of Earth's microbiomes.

The reconstruction of bacterial and archaeal genomes from shotgun metagenomes has enabled insights into the ecology and evolution of environmental and host-associated microbiomes. Here we applied this approach to >10,000 metagenomes collected from diverse habitats covering all of Earth's continents and oceans, including metagenomes from human and animal hosts, engineered environments, and natural and agricultural soils, to capture extant microbial, metabolic and functional potential. This comprehensive catalog includes 52,515 metagenome-assembled genomes representing 12,556 novel candidate species-level operational taxonomic units spanning 135 phyla. The catalog expands the known phylogenetic diversity of bacteria and archaea by 44% and is broadly available for streamlined comparative analyses, interactive exploration, metabolic modeling and bulk download. We demonstrate the utility of this collection for understanding secondary-metabolite biosynthetic potential and for resolving thousands of new host linkages to uncultivated viruses. This resource underscores the value of genome-centric approaches for revealing genomic properties of uncultivated microorganisms that affect ecosystem processes.

[Design of three-dimensional foraminal guide device and application in percutaneous endoscopic lumbar discectomy].

OBJECTIVE: To explore clinical application of the new three-dimensional foramen guide in percutaneous endoscopic lumbar discectomy. METHODS: Based on the principle of reverse positioning, a new three-dimensional foramen guide was designed. From May 2016 to May 2018, totally 40 patients with segmental lumbar disc herniation were underwent percutaneous endoscopic lumbar discectomy. The patients were divided into guide and control group, and 20 patients in each group. In guide group, there were 9 males and 11 females with an average age of (46.0±11.0) years old;5 patients on L3,4, 15 patients on L4,5; BMI was (25.4±3.2) kg /m2;three dimensional foramen guide was used to assist the operation. While in control group, there were 10 males and 10 females with an average age of (51.8±9.8) years old;4 patients on L3,4, 16 patients on L4,5;BMI was (24.8±3.5) kg /m2;the operation was completed with bare hands according to the experience. The puncture time, times of fluoroscopy and puncture between two groups were compared, as well as the preoperative and postoperative visual analogue scale (VAS) score and Japanese Orthopaedic Association (JOA) were compared. RESULTS: All patients had no serious complications, and successfully completed operation. Operation time, the times of fluoroscopy and puncture in guide group were better than those of control group (P<0.05). VAS score and JOA score between two groups were significantly relieved after operation (P<0.05), but there was no significant difference between two groups (P>0.05). CONCLUSION: The three dimensional foramen guide is compact in structure, simple in operation, which could reduce the time of puncture and damage of radiation, shorten the learning curve of puncture for beginners, and has certain clinical feasibility.

The integration of pore size and porosity distribution on Ti-6A1-4V scaffolds by 3D printing in the modulation of osteo-differentation.

PURPOSE: In this study, pore size and porosity distribution of porous Ti-6Al-4V scaffolds (pTi) were controlled by 3D printing. The effects of pore size distribution at a constant porosity, or porosity distribution at a constant pore size pertaining to functions of adhesion, proliferation, and differentiation of the mouse embryonic osteoblast precursor (MC3T3-E1) cells were researched separately. METHODS: 3D printing was used to design five groups of pTi, designated as PS300/HP, PS300/LP, PS500/HP, PS500/LP, and PS800/HP based on pore size and porosity distribution. MC3T3-E1 cells were cultured on pTi, and non-porous Ti-6Al-4V samples (npTi) were prepared as control. The pTi was characterized with the scanning electron microscopy (SEM). MC3T3-E1 cells were stained via AlamarBlue assay and viability and proliferation analyzed. The mRNA levels of alkaline phosphatase (ALP), osteocalcin (OCN), collagentype-1 (Col-1), and runt-related transcription factor 2 (Runx2) in MC3T3-E1 cells were analyzed by real-time PCR analysis. RESULTS: The average pore size and porosity of pTi were recorded as (301 ± 9 µm, 58.8 ± 1.8%), (300 ± 9 µm, 43.4 ± 1.3%), (501 ± 11 µm, 58.3 ± 1.2%), (499 ± 12 µm, 42.7 ± 1.1%), and (804 ± 10 µm, 58.9 ± 1.3%), respectively. SEM images confirmed active attachment of cells and oriented with the direction of metal rod after pTi/MC3T3-E1 co-culture for 3 and 7 days. In addition, MC3T3-E1 cells grown on the PS800/HP displayed significantly higher proliferation compared with each group after 3 days incubation (p < 0.05). Moreover, cells showed some degree of proliferation in all groups, with the highest value recorded for PS800/HP after culture for 7 days (p < 0.05). The gene expression pattern of ALP, OCN, Col-1, and Runx2 confirmed that these were down-regulated when pore size increased or porosity decreased of pTi (p < 0.05). CONCLUSION: The pTi facilitated the adhesion and differentiation of osteoblast when pore size decreased or porosity increased. The scaffold model resembles physical modification with porous structures, which has potential application in the surface modifications of Ti implant.

Pedicle Screw Insertion: Is O-Arm-Based Navigation Superior to the Conventional Freehand Technique? A Systematic Review and Meta-Analysis.

BACKGROUND: Although O-arm-based navigation (ON) has been considered a better choice than the conventional freehand (FH) technique for spine surgery, clinical evidence showing the accuracy of ON compared with the FH technique is limited. The purpose of this study was to evaluate the accuracy of pedicle screw insertion under ON compared with the FH technique. METHODS: The Cochrane Library, Ovid, Web of Science, PubMed, Embase, and CNKI online databases were searched up to January 2020. Because only a few randomized controlled trials were anticipated, prospective and retrospective comparative studies were also evaluated to compare the accuracy of pedicle screw insertion between ON and FH. Statistical analysis was performed using Stata 16.0. The primary outcomes extracted from articles that met the selection criteria were expressed as odds ratios for dichotomous outcomes with a 95% confidence interval. A χ2 test and I2 statistics were used to evaluate heterogeneity. RESULTS: A total of 20 reviews were included in this meta-analysis without identifying additional studies from the references of published articles. These reviews included 1422 patients and 9982 screws. ON was used to insert 4797 pedicle screws and 5185 pedicle screws were inserted using the conventional FH technique with C-arm assistance. The meta-analysis showed that ON is significantly more accurate than FH pedicle screw insertion (odds ratio, 2.46; 95% confidence interval, 1.92-3.16; I2 = 43.4%; P = 0.021). I2 indicates that the studies have a moderate statistical heterogeneity; subgroup analysis decreased heterogeneity significantly. CONCLUSIONS: Compared with conventional methods, navigation provides greater accuracy in the placement of pedicle screws, accelerates the insertion, and reduces the complications associated with screw insertion. However, it may increase exposure time to radiation, which may harm the patient's or surgeon's health.

Unilateral or Bilateral Percutaneous Endoscopic Debridement and Lavage Treatment for Lumbar Spinal Tuberculosis.

OBJECTIVE: To compare the clinical outcome between bilateral percutaneous endoscopic debridement and lavage (PEDL) and unilateral PEDL treatment for lumbar spine tuberculosis (LST). METHODS: A total of 40 patients with LST who underwent either bilateral PEDL (group A) or unilateral PEDL (group B) were reviewed. Perioperative parameters were assessed by operative time, intraoperative fluoroscopy times, and days of postoperative continuous irrigation and vacuum drainage. Clinical outcomes were evaluated in the Oswestry Disability Index (ODI), visual analog scale (VAS), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). All patients were followed-up for at least 18 months after treatment. RESULTS: The average operative time and intraoperative fluoroscopy time were increased in group A compared with those in group B. There was no statistical significance between the 2 groups in postoperative continuous irrigation and vacuum drainage days. The ESR and CRP curves in the 2 groups showed a similar trend during 18-month follow-up. The VAS and ODI in the 2 groups significantly decreased 6 and 18 months postsurgery. There was no significant difference in the incidence of complication between the 2 groups. CONCLUSIONS: Two procedures yielded comparable and satisfactory results. Unilateral PEDL showed shorter operative time and decreased intraoperative fluoroscopy times compared with bilateral PEDL. We suggest the use of unilateral PEDL rather than bilateral PEDL in the treatment of LST.

Intra-articular, single-shot co-injection of hyaluronic acid and corticosteroids in knee osteoarthritis: A randomized controlled trial.

The aim of the present study was to investigate whether the co-injection of hyaluronic acid (HA) and corticosteroids (CS) was superior to HA alone in the treatment of knee OA. A total of 120 participants with symptomatic knee OA were recruited and formed the intention-to-treat population for a 6-month follow-up. In the HA group, patients received a single-shot injection of 4 ml HA. In the HA&CS group, patients received a co-injection of 3 ml compound betamethasone solution and 4 ml HA. Visual analog scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and knee flexion motion were assessed as primary outcomes. Patients in the HA&CS group exhibited better pain relief and knee function at the time points of week 1, month 1 and month 3 (P<0.05). For the last follow-up at month 6, the values did not differ significantly between these two groups. Patients in both groups exhibited improvement in pain, knee function, and range of motion following injection. For the final follow-up at month 6, the mean VAS score, WOMAC score and knee flexion motion were still superior to that prior to treatment, but the values did not differ significantly. The co-injection of HA and CS provided a rapid improvement in pain relief, knee function, and range of motion, but did not differ significantly from that of HA alone in the long term effect.

Chondroprotective Effects of Ginsenoside Rg1 in Human Osteoarthritis Chondrocytes and a Rat Model of Anterior Cruciate Ligament Transection.

This study aimed to assess whether Ginsenoside Rg1 (Rg1) inhibits inflammatory responses in human chondrocytes and reduces articular cartilage damage in a rat model of osteoarthritis (OA). Gene expression and protein levels of type II collagen, aggrecan, matrix metalloproteinase (MMP)-13 and cyclooxygenase-2 (COX-2) were determined in vitro by quantitative real-time-polymerase chain reaction and Western blotting. Prostaglandin E2 (PGE2) amounts in the culture medium were determined by enzyme-linked immunosorbent assay (ELISA). For in vivo assessment, a rat model of OA was generated by anterior cruciate ligament transection (ACLT). Four weeks after ACLT, Rg1 (30 or 60 mg/kg) or saline was administered by gavage once a day for eight consecutive weeks. Joint damage was analyzed by histology and immunohistochemistry. Ginsenoside Rg1 inhibited Interleukin (IL)-1ß-induced chondrocyte gene and protein expressions of MMP-13, COX-2 and PGE2, and prevented type II collagen and aggrecan degradation, in a dose-dependent manner. Administration of Ginsenoside Rg1 to OA rats attenuated cartilage degeneration, and reduced type II collagen loss and MMP-13 levels. These findings demonstrated that Ginsenoside Rg1 can inhibit inflammatory responses in human chondrocytes in vitro and reduce articular cartilage damage in vivo, confirming the potential therapeutic value of Ginsenoside Rg1 in OA.

Human Umbilical Cord-Derived Mesenchymal Stromal Cells Improve Left Ventricular Function, Perfusion, and Remodeling in a Porcine Model of Chronic Myocardial Ischemia.

UNLABELLED: : Stem cell therapy has emerged as a new strategy for treatment of ischemic heart disease. Although umbilical cord-derived mesenchymal stromal cells (UC-MSCs) have been used preferentially in the acute ischemia model, data for the chronic ischemia model are lacking. In this study, we investigated the effect of UC-MSCs originated from Wharton's jelly in the treatment of chronic myocardial ischemia in a porcine model induced by ameroid constrictor. Four weeks after ameroid constrictor placement, the surviving animals were divided randomly into two groups to undergo saline injection (n = 6) or UC-MSC transplantation (n = 6) through the left main coronary artery. Two additional intravenous administrations of UC-MSCs were performed in the following 2 weeks to enhance therapeutic effect. Cardiac function and perfusion were examined just before and at 4 weeks after intracoronary transplantation. The results showed that pigs with UC-MSC transplantation exhibited significantly greater left ventricular ejection fraction compared with control animals (61.3% ± 1.3% vs. 50.3% ± 2.0%, p < .05). The systolic thickening fraction in the infarcted left ventricular wall was also improved (41.2% ± 3.3% vs. 46.2% ± 2.3%, p < .01). Additionally, the administration of UC-MSCs promoted collateral development and myocardial perfusion. The indices of fibrosis and apoptosis were also significantly reduced. Immunofluorescence staining showed clusters of CM-DiI-labeled cells in the border zone, some of which expressed von Willebrand factor. These results suggest that UC-MSC treatment improves left ventricular function, perfusion, and remodeling in a porcine model with chronic myocardial ischemia. SIGNIFICANCE: Ischemic heart disease is the leading cause of death worldwide. Many patients with chronic myocardial ischemia are not suitable for surgery and have no effective drug treatment; they are called "no-option" patients. This study finds that umbilical cord-derived mesenchymal stromal cells transplanted by intracoronary delivery combined with two intravenous administrations was safe and could significantly improve left ventricular function, perfusion, and remodeling in a large-animal model of chronic myocardial ischemia, which provides a new choice for the no-option patients. In addition, this study used clinical-grade mesenchymal stem cells with delivery and assessment methods commonly used clinically to facilitate further clinical transformation.

Thoracic Pedicle Screw Placement Guide Plate Produced by Three-Dimensional (3-D) Laser Printing.

BACKGROUND The aim of this study was to evaluate the accuracy and feasibility of an individualized thoracic pedicle screw placement guide plate produced by 3-D laser printing. MATERIAL AND METHODS Thoracic pedicle samples of 3 adult cadavers were randomly assigned for 3-D CT scans. The 3-D thoracic models were established by using medical Mimics software, and a screw path was designed with scanned data. Then the individualized thoracic pedicle screw placement guide plate models, matched to the backside of thoracic vertebral plates, were produced with a 3-D laser printer. Screws were placed with assistance of a guide plate. Then, the placement was assessed. RESULTS With the data provided by CT scans, 27 individualized guide plates were produced by 3-D printing. There was no significant difference in sex and relevant parameters of left and right sides among individuals (P>0.05). Screws were placed with assistance of guide plates, and all screws were in the correct positions without penetration of pedicles, under direct observation and anatomic evaluation post-operatively. CONCLUSIONS A thoracic pedicle screw placement guide plate can be produced by 3-D printing. With a high accuracy in placement and convenient operation, it provides a new method for accurate placement of thoracic pedicle screws.

Clinical Efficacy of Mudpack Therapy in Treating Knee Osteoarthritis: A Meta-Analysis of Randomized Controlled Studies.

OBJECTIVE: The objective of this study was to evaluate the clinical efficacy of mudpack therapy for the treatment of knee osteoarthritis and identify the likely factors associated with the high heterogeneity of combined studies. DESIGN: The Medline, Embase, and Cochrane Library databases were systematically searched for randomized controlled trials in which mudpack therapy was used to treat knee osteoarthritis. RESULTS: Ten publications that reported the results from a total of 1010 subjects were included in this meta-analysis. Meta-analysis of improvement in joint function at the final follow-up visit suggested, given that the follow-up time was less than 4 mos, that the combined effect size of four studies was -0.30 (-0.62 to 0.02) and the difference did not reach the level of statistical significance. When the follow-up time reached 4 mos, the combined effect size was -1.10 (-2.07 to -0.14) and the difference was significant. The I values of the two groups were 21.4% and 93.8%. CONCLUSION: Functional improvement of the knee joint in patients treated with mudpack therapy was not significantly different from that of control subjects at the end of the 4-mo follow-up. The quality of current publications was a factor causing heterogeneity.

Clinical Use of 3D Printing Guide Plate in Posterior Lumbar Pedicle Screw Fixation.

BACKGROUND This study aimed to evaluate the clinical efficacy of use of a 3D printing guide plate in posterior lumbar pedicle screw fixation. MATERIAL AND METHODS We enrolled 43 patients receiving posterior lumbar pedicle screw fixation. The experimental group underwent 3D printing guide plate-assisted posterior lumbar pedicle screw fixation, while the control group underwent traditional x-ray-assisted posterior lumbar pedicle screw fixation. After surgery, CT scanning was done to evaluate the accuracy of screw placement according to the Richter standard. RESULTS All patients were followed up for 1 month. The mean time of placement for each screw and the amount of hemorrhage was 4.9±2.1 min and 8.0±11.1 mL in the experimental group while 6.5±2.2 min and 59.9±13.0 mL in the control group, respectively, with significant differences (p<0.05). The fluoroscopy times of each screw placement was 0.5±0.4 in the experimental group, which was significantly lower than that in the control group 1.2±0.7 (p<0.05). The excellent and good screw placement rate was 100% in the experimental group and 98.4% in the control group, without any statistical difference (P>0.05). No obvious complications were reported in either group. CONCLUSIONS Compared with the traditional treatment methods, the intra-operative application of 3D printing guide plate can shorten the operation time and reduce the amount of hemorrhage. It can also reduce the fluoroscopy times compared with the traditional fluoroscopy, which cannot improve the accuracy rate of screw placement.

CD49f Acts as an Inflammation Sensor to Regulate Differentiation, Adhesion, and Migration of Human Mesenchymal Stem Cells.

The advent of mesenchymal stem cell (MSC)-based therapies has been an exciting innovation for the treatment of degenerative and inflammatory diseases. However, the surface markers that accurately reflect the self-renewal and differentiation potential of MSCs and their sensitivity to environmental cues remain poorly defined. Here, we studied the role of CD49f in bone marrow MSCs (BMSCs) and the mechanism by which it regulates the behavior of BMSCs under inflammatory conditions. We found that CD49f is preferentially expressed in fetal cells rather than adult cells, CD49f-positive BMSCs possess higher CFU-F formation ability and differentiation potential than CD49f negative cells, and the CD49f expression of BMSCs gradually decreases during in vitro passaging. CD49f knockdown dramatically decreased the differentiation of BMSCs and isoform A was demonstrated to be the main functional form that enhanced the differentiation ability of BMSCs. The influences of inflammatory cytokines on BMSCs revealed that TNF-α downregulated CD49f in BMSCs with impaired differentiation, decreased adhesion to laminins, and increased migration. Moreover, tissue transglutaminase was found to work together with CD49f to regulate the behavior of BMSCs. Finally, we showed that mTOR signaling rather than NF-κB activation mediated CD49f downregulation induced by TNF-α and maintained CD49f homeostasis in BMSCs. Our findings suggest that CD49f is a stemness marker of BMSCs and is tightly correlated with the behavioral changes of BMSCs under inflammatory conditions. These data demonstrate a novel role for CD49f in sensing inflammation through mTOR pathway to further modulate the behavior of MSCs to fulfill the requirements of the body.

Activation of α7 nicotinic acetylcholine receptors prevents monosodium iodoacetate-induced osteoarthritis in rats.

BACKGROUND/AIMS: Although some evidence suggests that the prevalence of osteoarthritis (OA) is lower in smokers compared to nonsmokers, the mechanisms of nicotine-induced protection remain unclear. Stimulation of the α7 nicotinic acetylcholine receptor (α7-nAChR) appears to be a critical mechanism underlying the anti-inflammatory potential of cholinergic agonists in immune cells. The inhibition of secreted inflammatory molecules and the subsequent inflammatory processes have been proposed as a novel strategy for the treatment of OA. The objective of the present study was to determine whether nicotine-induced protection in a monosodium iodoacetate (MIA) rat model of OA occurs via α7-nAChR-mediated inhibition of chondrocytes. METHODS: Both in vivo (MIA) and in vitro (MIA; Interleukin-1ß, IL-1ß) models of OA were used to investigate the roles and the possible mechanisms whereby α7-nAChRs protect against knee joint degradation. Multiple experimental approaches, including macroscopic, histological analysis, chondrocyte cell cultures, confocal microscopy, and western blotting, were employed to elucidate the mechanisms of α7-nAChR-mediated protection. RESULTS: Systemic administration of nicotine alleviated MIA-induced joint degradation. The protective effects of nicotine were abolished by administration of the α7-nAChR-selective antagonist methyllycaconitine (MLA). In primary cultured rat chondrocytes, pretreatment with nicotine suppressed both p38, extracellular regulated kinase (Erk) 1/2 and c-Jun-N-terminal kinase (JNK) mitogen-activated protein kinases (MAPK) phosphorylation and phosphorylated nuclear factor-kappa B (NF-κB) p65 activation induced by MIA- or IL-1ß, and these effects were also reversed by MLA. CONCLUSION: Taken together, our results suggest that activation α7-nAChRs is an important mechanism underlying the protective effects of nicotine.