bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-inflammatory Activities and Component Change of Processed and Fermented Gastrodiae Rhizoma
Authors: Park Shin Young , Kim Eun Ju , Song Bit Na , Jeong Da Som , Kim So Young , Park Bo Ram , Choi Han Seok 
Published: January 2023

Abstract
Gastrodiae Rhizoma (GR) is a traditional herbal medicine in Korea, China, and Japan, which has been used for the treatment of headaches, hypertension, oxidative stress, mental disorders, inflammation, and cardiovascular diseases. This study investigated the anti-infammatory activity and main component content of processed (PGR) and fermented Gastrodiae Rhizoma (FPGR). Processed method was soaked in vinegar solution until completely absorbed and steaming for 2 hours. Fermentation was carried out using Lactobacillus brevis and incubated at 37□ for 1~3 day. The anti-inflammatory activites were determine pro-inflammatory factors such as nuclear factor κB (NF-κB), nitric oxide (NO), prostaglandin E2 (PGE2), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-induced RAW 264.7 cell line and major functional components (gastrodin, gastrodigenin, vanillylalcohol, p-hydroxybenzaldehyde) were also measured. The results showed that the FPGR reduced NO, PGE2, iNOS, COX-2, NF-κB production without cytotoxicity and improved major components. These results suggest that FPGR extracts may be a developed the functional food related to anti-inflammation due to the significant effects on inflammatory facters. Therefore, fermented and processed Gastrodiae Rhizoma can be useful methods which can help applied as functional resources in the industrial area.
Identification of cytokine-specific sensory neural signals in murine vagus nerve activity recordings
Authors: Zanos Theodoros , Silverman Harold , Levy Todd , Tsaava Tea , Battinelli Emily , Lorraine Peter , Ashe Jeffrey , Chavan Sangeeta S. , Bouton Chad , Tracey Kevin J. 
Published: January 2023

Abstract
The nervous system maintains physiological homeostasis through reflex pathways that modulate organ function. This process begins when changes in the internal milieu (e.g. blood pressure, temperature, or pH) activate visceral sensory neurons that transmit action potentials along the vagus nerve to the brain stem. IL-1β and TNF, inflammatory cytokines produced by immune cells during infection and injury, and other inflammatory mediators have been implicated in activating sensory action potentials in the vagus nerve. However, it remains unclear whether neural responses encode cytokine-specific information. Here we develop methods to isolate and decode specific neural signals to discriminate between two different cytokines. Nerve impulses recorded from the vagus nerve of mice exposed to IL-1β and TNF were sorted into groups based on their shape and amplitude and their respective firing rates were computed. This revealed sensory neural groups responding specifically to TNF and IL-1β. These cytokine-mediated responses were subsequently decoded using a Naïve Bayes algorithm that discriminated between no exposure and exposures to IL-1β and TNF (mean successful identification rate 82.9±17.8%, chance level 33%). Recordings obtained in IL-1 receptor knockout mice were devoid of IL-1β related signals, but retained their responses to TNF. Genetic ablation of TRPV1 neurons attenuated the vagus neural signals mediated by IL-1β and distal lidocaine nerve block attenuated all vagus neural signals recorded. Using a novel methodological framework, the results obtained in this study suggest cytokine-specific information is present in sensory neural signals within the vagus nerve.
Gpr109a limits microbiota-induced IL-23 production to constrain ILC3-mediated colonic inflammation and carcinogenesis.
Authors: Bhatt Brinda , Zeng Peng , Zhu Huabin , Sivaprakasam Sathish , Xiao Haiyan , Dong Lixin , Shiao Pamela , Kolhe Ravindra , Li Honglin , Ganapathy Vadivel , Singh Nagendra 
Published: January 2023

Abstract
A set of coordinated interactions between gut microbiota and the immune cells surveilling the intestine play a key role in shaping local immune responses and intestinal health. There are several immunoregulatory mechanisms in place that prevent the needless activation of immune cells against harmless gut bacteria. The dysregulation of interleukin-23 (IL-23) plays a critical role in the induction of several inflammatory diseases including inflammatory bowel disease (IBD). However, the molecular mechanisms regulating IL-23 production are poorly characterized. Gpr109a is a G-protein coupled receptor that is expressed at a very high level on innate immune cells and has been previously shown to play a key role in the induction of colonic Tregs. We show that Gpr109a−/−Rag1−/− mice exhibit spontaneous rectal prolapse and colonic inflammation, as characterized by the presence of an elevated number of IL-17-producing Rorγt+ innate lymphoid cells (ILC3). The genetic deletion of Rorγt ameliorated the spontaneous colonic inflammation in Gpr109a−/−Rag1−/− mice. Gpr109a-deficient colonic dendritic cells promote ILC3 by producing higher amounts of IL-23. Antibiotics treatment to deplete gut microbiota decreased IL-23 production, ILC3, and colonic inflammation in Gpr109a−/−Rag1−/− mice. Administration of niacin, a Gpr109a agonist, suppressed both IL-23 production by colonic DCs and ILC3 count in a Gpr109a-dependent manner. Collectively, our data presents a model suggesting that targeting Gpr109a will be potentially beneficial in the suppression of IL-23 mediated immunopathologies.
Validation and discovery of mechanisms that promote vitiligo pathogenesis using single-cell RNA-sequencing of cells isolated from skin interstitial fluid
Authors: Strassner James P. , Gellatly Kyle J. , Rashighi Mehdi , Ahmed Maggi , McDonel Patrick , Garber Manuel , Harris John E. 
Published: January 2023

Abstract
Vitiligo is an autoimmune disease in which CD8+ T cells destroy melanocytes, leading to patchy, depigmented lesions of the skin. To investigate possible immune processes in the skin that could explain the patchy appearance of vitiligo inflammation, we performed single-cell RNA-sequencing on cells isolated from the skin using a modified suction blistering technique. We compared the transcriptomes of cells isolated from lesional and non-lesional skin of six vitiligo subjects with active, spreading lesions as well as normal skin from six healthy subjects. Using differential gene analysis to cluster more than 18,000 cell transcriptomes in an unbiased fashion, we were able to identify the cellular components of the skin: melanocytes, keratinocytes, and Langerhans cells, as well as subgroups of immune cells. Consistent with previous findings by our group and others, this approach revealed an IFNγ signature in vitiligo lesions. This method identified 87 ligand-receptor pairs that may promote vitiligo pathogenesis, including CXCR6 and CXCL16 that were just recently implicated in vitiligo. The data set also revealed that Langerhans cells actively express many genes which have known risk alleles for vitiligo, highlighting a potential pivotal role in the development of vitiligo. Overall, single-cell RNA-sequencing of the skin infiltrate in vitiligo lesions is providing robust data that confirms many previous findings, but adds additional layers of nuance missed by conventional studies of bulk material. This level of resolution will yield powerful insight into the identification of novel drug targets in previously unknown signaling pathways in vitiligo and other diseases of the skin.
Immune mechanisms in the pathogenesis of idiopathic anterior uveitis.
Authors: Bora Nalini S. , Matta Bharati , Bora Puran S. 
Published: January 2023

Abstract
Idiopathic anterior uveitis (IAU) is a blinding disease characterized by inflammation of the iris and the ciliary body (CB) of the eye. IAU is treated symptomatically only using non-specific therapies such as steroid and immunosuppressive agents. These treatment modalities do not address the underlying mechanisms and are associated with adverse side effects. Experimental autoimmune anterior uveitis (EAAU) is a clinically relevant animal model of human IAU. In the current study we used EAAU animal model to investigate underlying mechanisms involved in regulation of inflammation in IAU. EAAU was induced in Lewis rats by immunization with melanin associated antigen (MAA). We observed that Th17 cells (IL-17 producing CD4+ cells and CD4+RORγt+ cells) accumulated in rat eyes at the onset and the peak of the disease. During the resolution of EAAU, Th17 cells declined while CD4+CD25+FoxP3+ T regulatory (Tregs) cells accumulated in the eyes. Administration of recombinant TGF-β2 during the early stages of EAAU prevented the induction of uveitis by inhibiting CD4+T proliferation and increasing the number of CD4+CD25+FoxP3+ Tregs. Severity of active (on-going) EAAU was reduced only for the time of active treatment with TGF-β2. Adoptive transfer of CD4+CD25+ T regulatory cells after the onset of EAAU resulted in sharp decline in disease activity and early resolution of EAAU. In conclusion, our results demonstrate that TGF-β2 plays a pivotal role in regulation of intraocular inflammation in EAAU. Collectively, these results raise the possibility that human IAU can be treated perhaps by enhancing the generation of Tregs by TGF-β2. Additionally, Treg cell therapy is potentially a promising strategy in the treatment of established human IAU.
Novel insights into the puberty switch mechanisms of the sex bias in human asthma
Authors: Coden Mackenzie , Jeong Brian M. , Chiarella Sergio , Rodriguez Raul , Berdnikovs Sergejs 
Published: January 2023

Abstract
The gender bias in human asthma prevalence changes with puberty, with males having a higher asthma incidence before puberty and females having higher rates after. The mechanisms involved in this switch are unknown. Our previous research showed that multiple hormonal systems are dysregulated in allergic disease. Because sex hormones interact with all endocrine system axes, we hypothesized that non-sex hormones and their downstream functions in allergic disease are driven by sex related changes in puberty. Measuring non-sex hormone protein levels from human serum samples by multiplex ELISAs, we found a striking sexual dimorphism in endocrine regulation. Pre-puberty asthmatic males had higher T3, T4, and GH levels compared to healthy controls, and pre-puberty asthmatic females had lower C-peptide and insulin levels. Interestingly, we saw the opposite pattern post-puberty. In a kinetic murine ovalbumin asthma model, adult male mice had higher C-peptide and insulin baseline levels, which were maintained during inflammation. Males also had higher GIP levels in the acute phase and higher PP, PYY, and resistin levels in the model’s late phase. Since hormones regulate tissue homeostasis, we examined the puberty switch in key epithelial remodeling markers in the inflamed mouse lung. Thbs2, Nes, Postn, Tnc, and Wnt5a expression was different relative to baseline in both sexes pre-puberty, but only females had altered expression of these markers post-puberty. Interestingly, though the Th2 immune response was higher in females post-puberty, there was no sexual dimorphism pre-puberty. These results implicate that sex hormones exert systemic level regulation determining the age and gender dependent progression of asthma pathogenesis.
AKT targets CSK to regulate proximal BCR signaling in germinal center B cells
Authors: Luo Wei , Hawse William F. , Trivedi Nikita , Weisel Florian , Shlomchik Mark J. 
Published: January 2023

Abstract
We have recently shown (Luo et al., Immunity, in press) that, compared to naïve B cells (NBC), both B cell receptor (BCR) and CD40 signaling are rewired in germinal center (GC) B cells (GCBC). BCR signaling in GCBC induces only transient activation of Syk, leading to partial activation of the PI3K-AKT pathway, generating p-Foxo1 but not p-S6. There is minimal BCR-directed activation of other downstream pathways such as NF-κB. Conversely for CD40 ligation, only NF-κB but not PI3K is activated in GCBC. Initially we found that Lyn, the most upstream kinase in the BCR cascade, has more inhibitory vs activating phosphorylation in GCBC. To understand how this occurs, and why AKT targets only selected substrates in GCBC, we used an AKT-substrate-specific mAb to immunoprecipitate AKT targets in GCBC. We analyzed these by mass spectrometry to identify potential GCBC-specific AKT targets. This analysis revealed that AKT itself was retargeted in GCBC compared to NBC. In GCBC, AKT appeared to preferentially target negative regulators, including CSK, a kinase of the inhibitory Tyr of Lyn. In vitro kinase and functional studies confirmed that AKT could phosphorylate CSK. We then demonstrated that this phosphorylation results in markedly increased CSK enzymatic activity to phosphorylate Lyn. Consistent with this, we found Lyn activity in GC B cells is inhibited by CSK catalyzed phosphorylation. Critically, inhibiting AKT substantially enhanced activation vs inhibitory Tyr phosphorylation of Lyn, and enhanced Syk phosphorylation and downstream signals upon BCR stimulation in GCBC. Taken together, our findings identify and document a unique AKT negative feedback loop that dampens proximal BCR signaling in GC B cells.
Identification and functional analysis of NKp46+ natural killer cells from peripheral blood of squirrel (Saimiri sps.) and owl monkey (Aotus sps.)
Authors: Nehete Pramod N. , Chitta Sriram , Nehete Bharti Pramod , Vanchiere John A. , Abee Christian R. 
Published: January 2023

Abstract
Natural Killer (NK) cells as minor subsets of peripheral blood lymphocytes (PBL) are innate in nature to clear invading pathogens and tumor cells. Small rodent species to nonhuman primates and humans, immune systems consist of a spectrum of NK cell subsets with phenotype and functional diversity. This study examined NK cell subsets and expression of NKp46 in squirrel and owl monkeys, which are both New World primate species. Squirrel and owl monkeys are recommended by the World Health Organization as excellent experimental models for studies of malaria infection due to their susceptibility to some of the same strains that cause disease in humans and endemic viruses that are analogues of opportunistic human viruses. NK cells were identified from CD3 negative lymphocytes and sub-phenotyped by CD16 and CD8 expression, to classify CD8+ and CD8− NK cells and absolute numbers in peripheral blood were compared. Analysis of expression of NCR (Natural Cytotoxicity Receptors) proteins, NKp30 and NKp46 showed that NK cells from NHP had preferential expression of NKp46 over NKp30 and expression is mostly restricted to subset of CD8+ NK cells. Peripheral blood lymphocytes, enriched based on NKp46 expression, were further phenotyped as classic CD3−CD16+CD8+NK cells. Functional analysis of enriched cells was focused to verify whether subsets differ in cytolitic and/or “innate” in nature and to correlate with NCR protein expression. Enriched NK cells were co-cultured for stimulation with standard target cells including tumor cells and analyzed for cytokine production. The potential plasticity of peripheral blood NK cells in NHP based on steady state and/or inflammatory/pathogenic status of species will be analyzed and discussed.
Bisphenol-A diminishes neutrophil recruitment in zebrafish
Authors: Carson Sandra , Ohashi Sarah , Gerber Drew , Tieu Tam , Walser-Kuntz Evan , Walser-Kuntz Debby 
Published: January 2023

Abstract
The prevalent use of bisphenol-A (BPA) in food containers, thermal paper, and other products provides an environmental challenge to the immune system of both humans and wildlife as BPA disrupts estrogen activity and alters signaling. We are exploring the impact of in vivo BPA exposure on innate immunity in both mice and zebrafish. Our earlier work in C57BL/6J mice showed that low dose, in vivo BPA exposure significantly decreases LPS-induced expression of CXCL-1, a chemokine that recruits neutrophils to the site of infection and the mouse homolog of human IL-8, in spleen cells. To determine if reduced chemokine secretion has a functional outcome, we expanded our studies to the zebrafish embryo model. Real time PCR analysis indicates that 4 to 6 day post fertilization (dpf) zebrafish exposed to environmentally relevant doses of BPA show reduced background expression of CXCL-8, the zebrafish homolog of mouse CXCL-1, and a reduction in the total number of neutrophils (4 dpf). BPA exposure also reduces the upregulation of CXCL-8 induced by a tail cut injury in 4 dpf zebrafish. MPO::GFP zebrafish expressing GFP under a neutrophil-specific myeloperoxidase promoter were used to track neutrophil movement for six hours following a tail cut injury. 4 dpf zebrafish exposed to BPA show a significantly reduced neutrophil recruitment to the site of injury compared to controls (p=0.004), a finding which correlates with the reduction in injury-induced CXCL-8 expression. Together our findings demonstrate that BPA exposure during early zebrafish development diminishes two key innate immune responses, thus potentially increasing susceptibility to infection.
CD38: biomarker and functional role in human macrophages
Authors: Guerau-De-Arellano Mireia , Amici Stephanie A. , Young Nicholas , Papenfuss Tracey L. , Torrelles Jordi , Jarjour Wael 
Published: January 2023

Abstract
Macrophages mediate innate immune responses via a spectrum of phenotypes that range from inflammatory to resolving. We previously identified CD38 as a robust marker of inflammatory macrophages useful in both murine in vitro and in vivo models. We hypothesized that CD38 plays a similar biomarker and/or functional role in human macrophages and autoimmune inflammatory disease. Using human macrophages of primary or monocytic cell line origin, we found that CD38 is robustly induced in human macrophages exposed to LPS and IFN-g inflammatory stimuli, but not with the alternative stimulus, IL-4. Analyses in the systemic autoimmune disease Systemic Lupus Erythematosus (SLE) revealed that CD38hi classical and non-classical monocyte subpopulations are associated with disease activity. In addition, genetic or pharmacologic CD38 loss-of-function in human primary macrophages resulted in suppressed inflammatory cytokines IL-6 and IL-12p40 secretion in human primary macrophages. Taken together, these findings support a biomarker and functional role for CD38 in inflammatory macrophages/monocytes and inflammatory disease.
Glutathione Reductase Promotes Fungal Clearance and Suppresses Inflammation During Systemic Candida albicans Infection
Authors: Liu Yusen , Kim Victoria Y. , Li Jinhui , Batty Abel , Crowell Sara A. , Jin Yi , Zhang Jian , Nelin Leif D. 
Published: January 2023

Abstract
Glutathione reductase (Gsr) catalyzes the reduction of glutathione disulfide (GSSG) to glutathione (GSH), a major cellular antioxidant. We have previously shown that Gsr facilitates neutrophil bactericidal activities and is pivotal for host defense against bacterial pathogens. However, it is unclear whether Gsr is required for immune defense against fungal pathogens. It is also unclear whether Gsr plays a role in immunological functions outside of neutrophils. To address these questions, we studied the effect of Gsr knockout on immune defense against C. albicans. Upon infection by C. albicans, Gsr−/− mice displayed dramatically increased fungal burden in the kidneys, cytokine and chemokine storm, striking neutrophil infiltration and histological abnormalities in both the kidneys and hearts, and substantially elevated mortality. Large fungal foci surrounded by massive numbers of neutrophils were detected outside of glomerulus in the kidneys of Gsr−/− mice but were not found in wildtype mice. Examination of the neutrophils and macrophages of Gsr−/− mice also revealed several defects, including compromised phagocytosis, attenuated respiratory burst, and impaired fungicidal activity in Gsr−/− neutrophils in vitro. Moreover, upon C. albicans stimulation, Gsr−/− macrophages produced increased levels of inflammatory cytokines and exhibited elevated p38 and JNK activities, at least in part due to lower mitogen-activated protein kinase phosphatase (Mkp)-1 activity and greater Syk activity. Thus, Gsr-mediated redox regulation was found to be crucial for fungal clearance by neutrophils and the proper control of the inflammatory response by macrophages during host defense against fungal challenge.
Metabolic barriers underlie interferon gamma-mediated restriction of intracellular bacterial pathogenesis
Authors: Price Jordan , DiPeso Lucian , Nomura Daniel , Vance Russell E. 
Published: January 2023

Abstract
Interferon gamma (IFNγ) plays a critical role in controlling Legionella pneumophila (L. pneumophila) infection in vivo and in vitro. IFNγ and IFNγ receptor-deficient mice fail to clear L. pneumophila and eventually succumb to infection. In vitro, L. pneumophila replication is restricted in IFNγ-stimulated macrophages; however, the mechanism of IFNγ-dependent restriction of L. pneumophila remains mysterious and does not require most known IFNγ-driven antimicrobial pathways, including induction of autophagy and production of reactive nitrogen. As enhanced glycolysis is a notable metabolic characteristic of IFNγ and toll-like receptor-stimulated macrophages, we hypothesized that changes in macrophage metabolism are required for IFNγ-mediated restriction of L. pneumophila. Using a strain of L. pneumophila that is resistant to the glycolysis inhibitor 2-deoxyglucose (2DG), we were able to rescue bacterial growth in IFNγ-stimulated macrophages treated with 2DG. Interestingly, we observed that 2DG-mediated induction of the unfolded protein response appears to be more important than glycolysis inhibition in terms of interfering with IFNγ-mediated restriction of L. pneumophila. Our data suggest that metabolic shifts in IFNγ-stimulated macrophages could play a role in restriction of intracellular bacterial pathogen replication by altering the pool of available intracellular metabolites.
RAGE inhibitor prevents cognitive dysfunction and reduces inflammatory mediators in experimental pneumococcal meningitis
Authors: Generoso Jaqueline S. , Collodel Allan , Simões Lutiana Roque , Dagostin Caroline , Dominguini Diogo , Lodetti Bruna França , Giridharan Vijayasree V. , Michels Monique , Vieira Andriele , Dal-Pizzol Felipe , Barichello Tatiana 
Published: January 2023

Abstract
The inflammatory processes during pneumococcal meningitis increase the production of inflammatory mediators culminating with increased production and deposition of amyloid proteins. Our hypothesis is that the interaction of the RAGE-Aβ can stimulate multiple intracellular signaling pathways which leads to the inflammatory mediator’s production. This can lead to neuronal damage and impairment of the integrity of the blood-brain barrier (BBB) causing memory impairment and learning. Therapeutic strategies suggest that RAGE is an important target for the treatment of inflammatory diseases, since inflammation increases Aβ synthesis and regulates RAGE positively, and the activation of this pathway induces long-term cognitive dysfunction. The aim of this study was evaluated cytokines levels; BBB integrity; behavioral response and Aβ deposition, RAGE and high mobility group box-1 (HMGB-1) expression in adult Wistar rats after meningitis induction treated with RAGE-antagonist (FPS-ZM1). To evaluate the levels of tumor necrosis factor α (TNF-α), interleukin (IL) 1β, and IL-6 the animals were killed at 24 h; for BBB integrity were killed at 12, 18 and 24 h; for the behavioral and expression of RAGE, HMGB1 and Aβ the animals received treatment with ceftriaxone and were killed within 10 days after the induction of meningitis. In the tests the inhibition of RAGE with FPS-ZM1 decreased the cytokines production only prefrontal cortex, prevented the BBB break in 12, 18 and 24 h in the hippocampus and cerebral cortex, and decreased cognitive damage 10 days after meningitis induction. We demonstrate that bacterial meningitis may trigger cognitive impairment through up-regulation RAGE axis and RAGE-antagonist prevented cognitive impairment.