Exploring the environmental contamination toxicity and potential carcinogenic pathways of perfluorinated and polyfluoroalkyl substances (PFAS): An integrated network toxicology and molecular docking strategy.

The objective of this study was to investigate the potential carcinogenic toxicity and mechanisms of PFAS in thyroid, renal, and testicular cancers base on network toxicology and molecular docking techniques. Structural modeling was performed to predict relevant toxicity information, and compounds and cancer-related targets were screened in multiple databases. The interaction of PFAS with three cancers and their key protein targets were explored by combining protein network analysis, enrichment analysis and molecular docking techniques. PFOA, PFOS, and PFHXS exhibited significant carcinogenic and cytotoxic effects. These compounds may induce cancer by mediating active oxygen metabolism and the transduction of phosphatidylinositol 3-kinase/protein kinase B signaling pathway through genes such as ALB, mTOR, MDM2, and ERBB2. Furthermore, the underlying toxic mechanisms may be linked to the pathways in cancer, chemical carcinogenesis through reactive oxygen species/receptor activation, and the FoxO signaling pathway. The results contribute to a comprehensive understanding of the effects of these environmental pollutants on genes, proteins, and metabolic pathways in living organisms. It revealed their toxicity mechanisms in inducing thyroid, renal, and testicular cancers, and provided a solid theoretical foundation for designing new environmental control strategies and drug screening initiatives. Additionally, the integrated application of network toxicology and molecular docking technology can enhance our understanding of the toxicity and mechanisms of unknown environmental pollutants, which is beneficial for protecting the environment and human health.

Multi-omics and pharmacological characterization of patient-derived glioma cell lines.

Glioblastoma (GBM) is the most common brain tumor and remains incurable. Primary GBM cultures are widely used tools for drug screening, but there is a lack of genomic and pharmacological characterization for these primary GBM cultures. Here, we collect 50 patient-derived glioma cell (PDGC) lines and characterize them by whole genome sequencing, RNA sequencing, and drug response screening. We identify three molecular subtypes among PDGCs: mesenchymal (MES), proneural (PN), and oxidative phosphorylation (OXPHOS). Drug response profiling reveals that PN subtype PDGCs are sensitive to tyrosine kinase inhibitors, whereas OXPHOS subtype PDGCs are sensitive to histone deacetylase inhibitors, oxidative phosphorylation inhibitors, and HMG-CoA reductase inhibitors. PN and OXPHOS subtype PDGCs stably form tumors in vivo upon intracranial transplantation into immunodeficient mice, whereas most MES subtype PDGCs fail to form tumors in vivo. In addition, PDGCs cultured by serum-free medium, especially long-passage PDGCs, carry MYC/MYCN amplification, which is rare in GBM patients. Our study provides a valuable resource for understanding primary glioma cell cultures and clinical translation and highlights the problems of serum-free PDGC culture systems that cannot be ignored.

Clinical application of platelet rich plasma to promote healing of open hand injury with skin defect.

Background: Skin defects caused by open hand trauma are difficult to treat clinically and severely affect the recovery of hand function. Autologous platelet-rich plasma (PRP) has been widely used in the treatment of refractory chronic wounds, but its use in hand trauma skin defects remains scarce. Methods: This study compared the outcomes of 27 patients treated with PRP to 31 patients undergoing skin flap transplantation for hand wounds. We assessed several parameters, including healing times, duration of surgery, postoperative pain (VAS score), intraoperative amputation length, finger function, sensation restoration, nail bed preservation, and hospitalization expenses. Results: PRP-treated patients showed a mean healing time of 21.59 ± 3.17 days. Surgical times were significantly shorter in the PRP group (22.04 ± 7.04 min) compared to the flap group (57.45 ± 8.15 min, P < 0.0001). PRP patients experienced longer postoperative healing times (20.15 ± 2.16 days) than those in the skin flap group (12.84 ± 1.08 days, P < 0.0001), but reported lower pain scores (1.3 ± 1.44 vs 2.55 ± 2.06, P = 0.0119). Range of Motion (ROM) at the proximal interphalangeal joint was better in the PRP group (96.26° ± 6.69) compared to the flap group (86.16° ± 15.24, P = 0.0028). Sensory outcomes favored the PRP group, with a two-point discrimination of 2.37 ± 1.34 mm versus 2.52 ± 1.27 mm in the flap group (P = 0.0274). Costs were lower in the PRP group ($2081.6 ± 258.14 vs $2680.18 ± 481.15, P < 0.0001). Conclusion: PRP treatment for skin defects from hand trauma is effective, offering advantages in terms of reduced surgical time, pain, and cost, with comparable or superior functional outcomes to flap transplantation. Despite longer healing times, PRP may represent a preferable option for open hand injuries, preserving more nail beds and resulting in better sensation and joint motion.

Ginsenoside - a promising natural active ingredient with steroidal hormone activity.

Ginsenosides are a class of natural products with hormone-like activity of triterpenoid saponins and have a variety of pharmacological activities such as anti-aging, immune regulation and cognitive improvement. With the great research interest in alternative medicine and natural products, they are gradually becoming research hotspots. Ginsenosides have a four-ring rigid steroid backbone similar to steroid hormones, and a series of experimental studies have shown that they can exhibit hormone-like activity by binding to nuclear receptors or affecting hormone levels, thereby affecting a wide range of inflammatory conditions, cancers, and menopause-related diseases. This review summarizes the mechanisms and potential health effects of ginsenosides exhibiting estrogen-like, glucocorticoid-like and androgen-like activities, providing an important reference for the exploration of safe phytohormone replacement therapy.

Analysis of Polyphenol Extract from Hazel Leaf and Ameliorative Efficacy and Mechanism against Hyperuricemia Zebrafish Model via Network Pharmacology and Molecular Docking.

Hazel leaf, a by-product of hazelnuts, is commonly used in traditional folk medicine in Portugal, Sweden, Iran and other regions for properties such as vascular protection, anti-bleeding, anti-edema, anti-infection, and pain relief. Based on our previous studies, the polyphenol extract from hazel leaf was identified and quantified via HPLC fingerprint. The contents of nine compounds including kaempferol, chlorogenic acid, myricetin, caffeic acid, p-coumaric acid, resveratrol, luteolin, gallic acid and ellagic acid in hazel leaf polyphenol extract (ZP) were preliminary calculated, among which kaempferol was the highest with 221.99 mg/g, followed by chlorogenic acid with 8.23 mg/g. The inhibition of ZP on α-glucosidase and xanthine oxidase activities was determined via the chemical method, and the inhibition on xanthine oxidase was better. Then, the effect of ZP on hyperuricemia zebrafish was investigated. It was found that ZP obviously reduced the levels of uric acid, xanthine oxidase, urea nitrogen and creatinine, and up-regulated the expression ofOAT1 and HPRT genes in hyperuricemia zebrafish. Finally, the targeted network pharmacological analysis and molecular docking of nine polyphenol compounds were performed to search for relevant mechanisms for alleviating hyperuricemia. These results will provide a valuable basis for the development and application of hazel leaf polyphenols as functional ingredients.

Comparative Mitogenomic Analyses of Darkling Beetles (Coleoptera: Tenebrionidae) Provide Evolutionary Insights into tRNA-like Sequences.

Tenebrionidae is widely recognized owing to its species diversity and economic importance. Here, we determined the mitochondrial genomes (mitogenomes) of three Tenebrionidae species (Melanesthes exilidentata, Anatolica potanini, and Myladina unguiculina) and performed a comparative mitogenomic analysis to characterize the evolutionary characteristics of the family. The tenebrionid mitogenomes were highly conserved with respect to genome size, gene arrangement, base composition, and codon usage. All protein-coding genes evolved under purifying selection. The largest non-coding region (i.e., control region) showed several unusual features, including several conserved repetitive fragments (e.g., A+T-rich regions, G+C-rich regions, Poly-T tracts, TATA repeat units, and longer repetitive fragments) and tRNA-like structures. These tRNA-like structures can bind to the appropriate anticodon to form a cloverleaf structure, although base-pairing is not complete. We summarized the quantity, types, and conservation of tRNA-like sequences and performed functional and evolutionary analyses of tRNA-like sequences with various anticodons. Phylogenetic analyses based on three mitogenomic datasets and two tree inference methods largely supported the monophyly of each of the three subfamilies (Stenochiinae, Pimeliinae, and Lagriinae), whereas both Tenebrioninae and Diaperinae were consistently recovered as polyphyletic. We obtained a tenebrionid mitogenomic phylogeny: (Lagriinae, (Pimeliinae, ((Tenebrioninae + Diaperinae), Stenochiinae))). Our results provide insights into the evolution and function of tRNA-like sequences in tenebrionid mitogenomes and contribute to our general understanding of the evolution of Tenebrionidae.

Hazelnut and its by-products: A comprehensive review of nutrition, phytochemical profile, extraction, bioactivities and applications.

As output of hazelnut increases worldwide, so does the amount of by-products, leading to huge waste and environmental stress. This paper focuses on the varieties of hazelnut that have been studied more in the past two decades, and summarizes the research status of hazelnut and its by-products from the aspects of nutritional value, phytochemicals, extraction methods, biological functions and applications. Hazelnut and its by-products are rich in a variety of bioactive constituents, mainly polyphenols, which have antioxidant, antibacterial and prebiotic effects. Moreover, hazelnut shells, husks, and leaves contain taxanes such as paclitaxel, which can inhibit the proliferation of cancer cells. They are potentially good natural sources of paclitaxel compared to the slower growing yew. Therefore, it is essential to further integrate the extraction techniques and health-promoting properties of these nutrients and bioactive substances to expand their application and enhance their value.

UPLC-MS/MS profiling, antioxidant and anti-inflammatory activities, and potential health benefits prediction of phenolic compounds in hazel leaf.

Hazel leaf, one of the by-products of hazelnut, which is widely used in traditional folk medicine around the world. In the present study, the profile of free, conjugated, and bound phenolic compounds from hazel leaf was detected and their antioxidant and anti-inflammatory activities were investigated. The potential health benefits of different phenolic compounds were also predicted. The results showed that the 35 phenolic substances of free, conjugated and bound forms were identified including phenolic acids, flavonoids and catechins. Most of the hazel leaf phenolics were presented in free form, followed by conjugated and bound form. All the fractions effectively inhibited the production of reactive oxygen species and malondialdehyde in TBHP-stimulated human umbilical vein endothelial cells by enhancing endogenous superoxide dismutase, and accordingly alleviated inflammatory cytokines (NO, IL-1ß, TNF-α, and IL-6) in LPS-stimulated RAW264.7 cells, showing obvious antioxidant and anti-inflammatory capacity. Moreover, combined with network pharmacology, the potential therapeutic effects and functional pathways of hazel leaf phenolics were predicted, which provided value basis for exploring their treatment on diseases and developing health products in the future.

Comparative assessment of environmental impacts, mitigation potentials, and economic benefits of rain-fed and irrigated apple production systems on China's Loess Plateau.

Although the repaid development of China's apple industry heavily depends on excessive fertilizer-water-pesticide (FWP) inputs, little information is available that systematically evaluates environmental impacts, mitigation potential, and economical benefits of apple production systems in China. In this study, life cycle assessment (LCA) was conducted to elucidate environmental risks and mitigation potentials of rain-fed and irrigated apple production systems on China's Loess Plateau based on survey data from 847 farmers, and economic benefits were analyzed simultaneously. Results showed that irrigated orchards caused more severe environmental risks associated with energy depletion (ED), global warming potential (GWP) and acidification potential (AP) than those in rain-fed orchards, whereas an opposite was true for eutrophication potential (EP), human toxicity potential (HTP), aquatic toxicity potential (ATP) and soil toxicity potential (STP). ED and GWP occurred primarily in the agricultural material stage, while AP, EP, HTP, ATP, and STP occurred mostly in the orchard management stage. Optimized FWP management can markedly mitigate environmental impacts in both irrigated and rain-fed orchard systems. Synthetic fertilizer, because of production and field-associated emissions, was the greatest contributor to environmental impacts of an apple production system. An environmental pollution index (EPI) that integrated environmental categories was highest in conventional irrigated orchards (0.946), followed by conventional rainfed orchards (0.857), and optimized irrigated orchards (0.459), and the lowest EPI was in optimized rainfed orchards (0.389). Economic analysis revealed that the benefits of rainfed orchards were higher than those of irrigated orchards because of higher apple prices and lower labor costs. Optimized FWP management sharply decreased input costs, thereby substantially increasing net income in irrigated and rain-fed apple orchards. Overall, severe environmental risk and large mitigation potential co-exist in rain-fed and irrigated apple orchards on China's Loess Plateau. Integrated soil-crop-market management potentially exhibited considerable environmental and economic advantages, thereby efficiently developing high-quality apple production.

Study on the regulatory effect of leech peptide HE-D on macrophages in atherosclerosis by transcriptome sequencing.

ETHNOPHARMACOLOGICAL RELEVANCE: The incidence of atherosclerotic cardiovascular disease is a serious threat to human health. Leeches are used in traditional Chinese medicine to treat cardiovascular diseases. HE-D is an active peptide extracted and isolated from leeches, which can inhibit the migration of RAW264.7 macrophages. AIM: This study shows the effects of HE-D on macrophages in atherosclerosis and the mechanism of inhibition on the migration of macrophages based on transcriptome sequencing (RNA-Seq). MATERIALS AND METHODS: The transwell method was used to detect the activity of HE-D in inhibiting the migration of macrophages. Macrophages were divided into control group, lipopolysaccharide group, and HE-D group. Samples were collected and RNA-Seq performed. The DEseq2 method detected significantly differentially expressed genes (DEGs), GO and KEGG Pathway databases were used to analyze the functions and pathway enrichment of DEGs. Finally, qRT-PCR and Western blotting were used to verify the genes screened by RNA-Seq analyses. RESULTS: Cell experiments showed that HE-D can inhibit the migration of RAW264.7 macrophages induced by LPS. DEseq2 analyses showed that there were 363 DEGs after HE-D administration in the result of RNA-Seq. The GO function of DEGs was significantly enriched in cell migration and inflammation, and the DEGs related to cell migration were significantly enriched in the NF-κB signaling pathway. qRT-PCR and Western blot analyses, showed that when compared with the LPS group, the related genes IKKα, IKKγ, TRAF6, TLR4, and TRAF5 in the NF-κB pathway were significantly down-regulated in the HE-D group. In addition, it was found that the inflammatory factors iNOS and TNF-α were significantly down-regulated, and Arg-1 and IL-10 were up-regulated. CONCLUSION: HE-D can inhibit the migration of macrophages by inhibiting IKKα and IKKγ in the NF-κB signaling pathway, and promote the transformation of macrophages from M1to M2 subtypes. Therefore, HE-D can potentially be used as a drug for the treatment of atherosclerosis.

Electrochemically enhanced adsorption of organic dyes from aqueous using a freestanding metal-organic frameworks/cellulose-derived porous monolithic carbon foam.

Monolithic carbon foams are promising materials for adsorption due to the easy recyclability and without secondary-pollution. However, poor adsorption efficiency for organic pollutants limits its practical application. Hence, this work proposed a novel monolithic porous carbon foam by a facile carbonization approach as freestanding electrodes to remove the organic dyes. The prepared carbon foam derived from waste cigarette filters and zeolitic-imidazolate frameworks-8 with well-developed pores, and the calculated surface area is 1457 m2·g-1, and exhibited an outstanding removal efficiency for methylene blue in aqueous. The maximum adsorption capacity for methylene blue can reach up to 1846.7 mg·g-1 under the applied voltage of -1.2 V. Importantly, as-prepared carbon foams possessed excellent stability, and the removal efficiency can remain above 85% after 5 cycles. Thus, obtained porous carbon foams in this paper as a free standing electrode is expected to be promising materials of adsorbent besides supercapacitors.

Ginsenoside CK Inhibits TGF-ß-Induced Epithelial-Mesenchymal Transition in A549 Cell via SIRT1.

Ginsenoside CK is the main metabolite of protopanaxadiol saponins in intestinal bacteria. Previous studies have shown that ginsenoside CK can affect many aspects of tumor development through a variety of mechanisms. However, few studies have reported the antimetastatic effects of ginsenoside CK in non-small-cell lung cancer (NSCLC). In this study, we explored the effect of ginsenoside CK on epithelial-mesenchymal transition (EMT) induced by TGF-ß in A549 cells and the potential molecular mechanisms. Our data showed that ginsenoside CK effectively prevented TGF-ß-induced EMT, as indicated by the upregulation of E-cadherin and downregulation of vimentin. Furthermore, ginsenoside CK inhibited the metastatic ability of A549 cells in the tail vein lung metastasis model of nude mice. Additionally, ginsenoside CK decreased the expression of silent information regulator 2 homolog 1 (SIRT1) in the inhibition of EMT induced by TGF-ß. Moreover, the antimetastatic effect of ginsenoside CK was reversed by SIRT1 overexpression. Generally, our results indicated the antimetastatic effect and underlying mechanism of ginsenoside CK on TGF-ß-induced EMT in A549 cells, suggesting that ginsenoside CK can be used as an effective antineoplastic agent.

GR-mediated anti-inflammation of α-boswellic acid: Insights from in vitro and in silico studies.

Although multiple bioactivities of α-boswellic acid have been reported, the molecular mechanism of its anti-inflammatory action is not yet clear. Hence, glucocorticoid receptor (GR)-mediated anti-inflammation of α-boswellic acid was investigated in this work. Fluorescence polarization assay suggested that α-boswellic acid bound to GR with IC50 value of 658.00 ± 0.21 µM. Upon binding to α-boswellic acid, GR translocated from cytoplasm into nucleus of HeLa cells, facilitating sequential transcriptional regulation of GR-related genes. Luciferase reporter assay suggested that α-boswellic acid lacked GR transcriptional activity, indicating its potential as a dissociative GR ligand. Interestingly, α-boswellic acid selectively modulated the anti-inflammatory gene CBG (marker for GR transrepression), while leaving the "side-effect" gene TAT (marker for GR transactivation) unaffected in HepG2 cells. Furthermore, α-boswellic acid inhibited lipopolysaccharide-stimulated cytokines production in U937 macrophages, confirming its anti-inflammation property in vitro. Molecular docking showed that both hydrogen-bonding and hydrophobic interactions helped to stabilize α-boswellic acid-GR binding. Their binding stability was further confirmed in a 70-ns dynamics simulation. In summary, α-boswellic acid could bind to and translocate GR but did not induce glucocorticoid response element-mediated transcription. Since α-boswellic acid showed the dissociated characteristic that separated transrepression from transactivation, it might be a selective GR modulator against inflammatory disorders.

Advances in Studies on the Pharmacological Activities of Fucoxanthin.

Fucoxanthin is a natural carotenoid derived mostly from many species of marine brown algae. It is characterized by small molecular weight, is chemically active, can be easily oxidized, and has diverse biological activities, thus protecting cell components from ROS. Fucoxanthin inhibits the proliferation of a variety of cancer cells, promotes weight loss, acts as an antioxidant and anti-inflammatory agent, interacts with the intestinal flora to protect intestinal health, prevents organ fibrosis, and exerts a multitude of other beneficial effects. Thus, fucoxanthin has a wide range of applications and broad prospects. This review focuses primarily on the latest progress in research on its pharmacological activity and underlying mechanisms.

Inference of Subpathway Activity Profiles Reveals Metabolism Abnormal Subpathway Regions in Glioblastoma Multiforme.

Glioblastoma, also known as glioblastoma multiforme (GBM), is the most malignant form of glioma and represents 81% of malignant brain and central nervous system (CNS) tumors. Like most cancers, GBM causes metabolic recombination to promote cell survival, proliferation, and invasion of cancer cells. In this study, we propose a method for constructing the metabolic subpathway activity score matrix to accurately identify abnormal targets of GBM metabolism. By integrating gene expression data from different sequencing methods, our method identified 25 metabolic subpathways that were significantly abnormal in the GBM patient population, and most of these subpathways have been reported to have an effect on GBM. Through the analysis of 25 GBM-related metabolic subpathways, we found that (S)-2,3-Epoxysqualene, which was at the central region of the sterol biosynthesis subpathway, may have a greater impact on the entire pathway, suggesting a potential high association with GBM. Analysis of CCK8 cell activity indicated that (S)-2,3-Epoxysqualene can indeed inhibit the activity of U87-MG cells. By flow cytometry, we demonstrated that (S)-2,3-Epoxysqualene not only arrested the U87-MG cell cycle in the G0/G1 phase but also induced cell apoptosis. These results confirm the reliability of our proposed metabolic subpathway identification method and suggest that (S)-2,3-Epoxysqualene has potential therapeutic value for GBM. In order to make the method more broadly applicable, we have developed an R system package crmSubpathway to perform disease-related metabolic subpathway identification and it is freely available on the GitHub (https://github.com/hanjunwei-lab/crmSubpathway).

Advances in the Study of Marine Products with Lipid-Lowering Properties.

With twice the number of cancer's deaths, cardiovascular diseases have become the leading cause of death worldwide. Atherosclerosis, in particular, is a progressive, chronic inflammatory cardiovascular disease caused by persistent damage to blood vessels due to elevated cholesterol levels and hyperlipidemia. This condition is characterized by an increase in serum cholesterol, triglycerides, and low-density lipoprotein, and a decrease in high-density lipoprotein. Although existing therapies with hypolipidemic effects can improve the living standards of patients with cardiovascular diseases, the drugs currently used in clinical practice have certain side effects, which insists on the need for the development of new types of drugs with lipid-lowering effects. Some marine-derived substances have proven hypolipidemic activities with fewer side effects and stand as a good alternative for drug development. Recently, there have been thousands of studies on substances with lipid-lowering properties of marine origin, and some are already implemented in clinical practice. Here, we summarize the active components of marine-derived products having a hypolipidemic effect. These active constituents according to their source are divided into algal, animal, plant and microbial and contribute to the development and utilization of marine medicinal products with hypolipidemic effects.

Neural-specific distribution of transmembrane protein TMEM240 and formation of TMEM240-Body.

Mutation in TMEM240 is suggested to cause SCA21, but the specific mechanism has not been clarified. The subcellular localization, specific biological function, and corresponding mechanism of action of TMEM240 have also not been delineated. In this study, the mRNA and protein expression of TMEM240 were assessed using qPCR and western blotting, respectively. Live cell imaging was used to establish the sub-cellular location of TMEM240, and electron microscopy was used to determine the morphology and distribution of TMEM240 in the cell. TMEM240 was specifically expressed in the neurons. Exogenous TMEM240 formed a multilayered cell structure, which we refer to as TMEM240-Body (T240-Body). T240-Body was separated and purified by centrifugation and filtration. An anchor protein His-tagged-GFP-BP on Ni-NTA agarose was used to pull down T240-GFP binding proteins. Both the N-terminal and the C-terminal of TMEM240 were confirmed to be inside the T240-Body. Co-localization experiments suggested that peroxisomes might contribute to T240-Body formation, and the two transmembrane regions of TMEM240 appear to be essential for formation of the T240-Body. Emerin protein contributed to formation of T240-Body when combined with TMEM240. Overall, this study provides new insights into TMEM240, which inform future research to further our understanding of its biological function.

Advances in Research on the Bioactivity of Alginate Oligosaccharides.

Alginate is a natural polysaccharide present in various marine brown seaweeds. Alginate oligosaccharide (AOS) is a degradation product of alginate, which has received increasing attention due to its low molecular weight and promising biological activity. The wide-ranging biological activity of AOS is closely related to the diversity of their structures. AOS with a specific structure and distinct applications can be obtained by different methods of alginate degradation. This review focuses on recent advances in the biological activity of alginate and its derivatives, including their anti-tumor, anti-oxidative, immunoregulatory, anti-inflammatory, neuroprotective, antibacterial, hypolipidemic, antihypertensive, and hypoglycemic properties, as well as the ability to suppress obesity and promote cell proliferation and regulate plant growth. We hope that this review will provide theoretical basis and inspiration for the high-value research developments and utilization of AOS-related products.

Enhancement of T Follicular Helper Cell-Mediated Humoral Immunity Reponses During Development of Experimental Autoimmune Myasthenia Gravis.

Myasthenia gravis (MG) is a prototypical antibody-mediated neurological autoimmune disease with the involvement of humoral immune responses in its pathogenesis. T follicular helper (Tfh) cells have been implicated in many autoimmune diseases. However, whether and how Tfh cells are involved in MG remain unclear. Here, we established and studied a widely-used and approved animal model of human MG, the rat model with acetylcholine receptor alpha (AChRα) subunit (R-AChR97-116)-induced experimental autoimmune myasthenia gravis (EAMG). This model presented mild body-weight loss 10 days after the first immunization (representing the early stage of disease) and more obvious clinical manifestations and body-weight loss 7 days after the second immunization (representing the late stage of disease). AChR-specific pre-Tfh cells and mature Tfh cells were detected in these two stages, respectively. In co-cultures of Tfh cells and B cells, the number of IgG2b-secreting B cells and the level of anti-AChR antibodies in the supernatant were higher in the cultures containing EAMG-derived Tfh cells. In immunohistochemistry and immunofluorescence assays, a substantial number of CD4+/Bcl-6+ T cells and a greater number of larger germinal centers were observed in lymph node tissues resected from EAMG rats. Based on these results, we hypothesize that an AChR-specific Tfh cell-mediated humoral immune response contributes to the development of EAMG.

Exogenous IL-9 Ameliorates Experimental Autoimmune Myasthenia Gravis Symptoms in Rats.

Interleukin-9 (IL-9) is a multifunctional cytokine involved in protective immunity or immunopathology depending on the microenvironment and specific disease settings. Our early study determined that IL-9 and Th9 cells participate in and promote the progression of experimental autoimmune myasthenia gravis (EAMG). The data from this study showed that exogenous recombinant rat IL-9 (rrIL-9) acted as an IL-9 receptor antagonist, reduced the incidence of EAMG in rats, alleviated the severity of the disease, and reduced the anti-acetylcholine receptor (AChR) IgG antibody levels by altering the Th-subset distribution. These data suggest that administration of rrIL-9 may provide a novel therapeutic strategy against MG or related autoimmune diseases. Abbreviations: 2-Mercaptoethanol (2-ME); antibodies (Abs); ?-bungarotoxin (?-BTX); acetylcholine receptor (AChR); airway hyper-reactivity (AHR); allophycocyanin-conjugated (APC); antigen presenting cells (APCs); complete Freund's adjuvant (CFA); Cyanine dye 3 (Cy3); dendritic cells (DCs); experimental autoimmune encephalomyelitis (EAE); experimental autoimmune myasthenia gravis (EAMG); flow cytometry (FACS); fetal bovine serum (FBS); fetal calf serum (FCS); Fluorescein isothiocyanate (FITC); gamma chain (?c); intraperitoneally (i.p.); Incomplete Freund's adjuvant (IFA); interferon (IFN); immunoglobulin (Ig); Interleukin (IL); Janus kinase (JAK); myasthenia gravis (MG); Mononuclear cells (MNC); neuromuscular junctions (NMJ); optical density (OD); ovalbumin (OVA); phosphate-buffered saline (PBS); phycoerythrin (PE); Peridinin chlorophyll protein complex (Percp); Rat AChR ? subunit (R-AChR97-116); Recombinant Rat (rr); room temperature (RT); signal transducer and activator of transcription (STAT); T helper cells (Th).