Mesenchymal stem cells preconditioned with a TLR5 agonist enhanced immunoregulatory effect through M2 macrophage polarization in a murine graft-versus-host disease model.

Graft-versus-host disease (GVHD) is a common complication following hematopoietic stem cell transplantation and can be life-threatening. Mesenchymal stem cells (MSCs), adult stem cells with immunomodulatory properties, have been used as therapeutic agents in a variety of ways and have demonstrated efficacy against acute GVHD (aGVHD); however, variability in MSC pro- and anti-inflammatory properties and the limitation that they only exhibit immunosuppressive effects at high levels of inflammation have prevented their widespread clinical use. The outcomes of GVHD treated with MSCs in the clinic have been variable, and the underlying mechanisms remain unclear.

TLR5 agonist in combination with anti-PD-1 treatment enhances anti-tumor effect through M1/M2 macrophage polarization shift and CD8 T cell priming.

Immune checkpoint inhibitors have revolutionized anti-tumor therapy, notably improving treatment responses in various tumors. However, many patients remain non-responsive and do not experience benefits. Given that Toll-like receptors (TLRs) can counteract tumor immune tolerance by stimulating both innate and adaptive immune responses, TLR agonists are being explored as potential immune adjuvants for cancer treatment.

Processing wh-filler-gap dependencies.

We present experimental evidence showing that different wh-filler-gap dependencies are processed differently, depending on their syntactic licensors. Our studies compared the active storage profiles for , , and (serving as subject or object of the verb). The results of offline and online experiments revealed that these wh-fillers are stored in memory for different durations, and predictably so based on the hypothesised structural distance between each wh-filler and the licensor which determines its grammatical and interpretive functions.

Zero-derivation in Korean: the effect of covert structure in real-time processing.

Korean words like 'bright/become bright' and 'long/become long' are categorially ambiguous; they can appear as both adjectives and verbs. Some suggest that these words are listed under separate lexical entries, while others propose that they share one single lexical entry, and that the verb form is morphologically derived from the base adjective through a process called zero derivation. This study presents the results of a real-time experiment that investigates whether these words involve zero derivation and if so, how zero derivation may affect the real-time processing of these words.

HMBA ameliorates obesity by MYH9- and ACTG1-dependent regulation of hypothalamic neuropeptides.

The global epidemic of obesity remains a daunting problem. Here, we report hexamethylene bisacetamide (HMBA) as a potent anti-obesity compound. Peripheral and central administration of HMBA to diet-induced obese mice regulated the expression of hypothalamic neuropeptides critical for energy balance, leading to beneficial metabolic effects such as anorexia and weight loss.

Island-sensitivity of two different interpretations of in Chinese.

It has been assumed that the -element "why" in Chinese has two distinct interpretations: a reason reading, which typically yields "because"-answers, and a purpose reading, which typically triggers "in order to"-answers. It is claimed that the two interpretations differ in island sensitivity: the reason is sensitive to islands while the purpose is not. Assuming that the reason is a -adverb without finer internal structure, while the purpose is a -PP consisting of the preposition "for" and a -DP "what," this contrast in island sensitivity can be considered as an instance of a broader generalization: the so-called argument-adjunct asymmetry (or the DP-adverb asymmetry) of - island sensitivity.

BAFF blockade attenuates acute graft-versus-host disease directly the dual regulation of T- and B-cell homeostasis.

Introduction: B-cell-activating factor (BAFF) is associated with donor-specific antibodies and chronic graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the effects of BAFF on T-cell physiological function have not been fully elucidated in acute GVHD.

Methods: We examined the effects of belimumab, a monoclonal antibody targeting BAFF, for the treatment of acute GVHD.

The Puzzle of Argument Structure Mismatch in Gapping.

Voice mismatch between conjuncts is impossible in the gapping construction. Some recent studies explained this effect by analyzing gapping as involving the ellipsis of a category at least as large as VoiceP. One prediction this analysis makes is that mismatch of any head structurally lower than Voice (e.

Off-the-Shelf Partial HLA Matching SARS-CoV-2 Antigen Specific T Cell Therapy: A New Possibility for COVID-19 Treatment.

Background: Immunological characteristics of COVID-19 show pathological hyperinflammation associated with lymphopenia and dysfunctional T cell responses. These features provide a rationale for restoring functional T cell immunity in COVID-19 patients by adoptive transfer of SARS-CoV-2 specific T cells.

Methods: To generate SARS-CoV-2 specific T cells, we isolated peripheral blood mononuclear cells from 7 COVID-19 recovered and 13 unexposed donors.

Auranofin prevents liver fibrosis by system Xc-mediated inhibition of NLRP3 inflammasome.

Demand for a cure of liver fibrosis is rising with its increasing morbidity and mortality. Therefore, it is an urgent issue to investigate its therapeutic candidates. Liver fibrosis progresses following 'multi-hit' processes involving hepatic stellate cells, macrophages, and hepatocytes.

Human mesenchymal stem cells derived from umbilical cord and bone marrow exert immunomodulatory effects in different mechanisms.

Background: Mesenchymal stem cells (MSCs) are an attractive tool to treat graft-versus-host disease because of their unique immunoregulatory properties. Although human bone marrow-derived MSCs (BM-MSCs) were the most widely used MSCs in cell therapy until recently, MSCs derived from human umbilical cords (UC-MSCs) have gained popularity as cell therapy material for their ethical and noninvasive collection.

Aim: To investigate the difference in mechanisms of the immunosuppressive effects of UC-MSCs and BM-MSCs.

Processing gapping: Parallelism and grammatical constraints.

This study aims to test two hypotheses about the online processing of Gapping: whether the parser inserts an ellipsis site in an incremental fashion in certain coordinated structures (the Incremental Ellipsis Hypothesis), or whether ellipsis is a late and dispreferred option (the Ellipsis as a Last Resort Hypothesis). We employ two offline acceptability rating experiments and a sentence fragment completion experiment to investigate to what extent the distribution of Gapping is controlled by grammatical and extra-grammatical constraints. Furthermore, an eye-tracking while reading experiment demonstrated that the parser inserts an ellipsis site incrementally but only when grammatical and extra-grammatical constraints allow for the insertion of the ellipsis site.

Tanycytic TSPO inhibition induces lipophagy to regulate lipid metabolism and improve energy balance.

Unlabelled: Hypothalamic glial cells named tanycytes, which line the 3 ventricle (3V), are components of the hypothalamic network that regulates a diverse array of metabolic functions for energy homeostasis. Herein, we report that TSPO (translocator protein), an outer mitochondrial protein, is highly enriched in tanycytes and regulates homeostatic responses to nutrient excess as a potential target for an effective intervention in obesity. Administration of a TSPO ligand, PK11195, into the 3V, and tanycyte-specific deletion of reduced food intake and elevated energy expenditure, leading to negative energy balance in a high-fat diet challenge.

Down-regulation of intracellular reactive oxygen species attenuates P-glycoprotein-associated chemoresistance in Epstein-Barr virus-positive NK/T-cell lymphoma.

Epstein-Barr virus (EBV)-positive extranodal NK/T-cell lymphoma is a rare and highly aggressive disease with a poor prognosis and strong resistance to anti-cancer drugs. Reactive oxygen species (ROS) are closely related to tumorigenesis and P-glycoprotein (P-gp) is highly expressed in various cancers. However, the exact relationship between ROS and P-gp in EBV-positive lymphoma remains unclear.

Regulation of HMGB1 release protects chemoradiotherapy-associated mucositis.

Oral mucositis (OM) is a common complication in cancer patients undergoing anticancer treatment. Despite the clinical and economic consequences of OM, there are no drugs available for its fundamental control. Here we show that high-mobility group box 1 (HMGB1), a "danger signal" that acts as a potent innate immune mediator, plays a critical role in the pathogenesis of OM.

Enhancement of Graft-Versus-Host Disease Control Efficacy by Adoptive Transfer of Type 1 Regulatory T Cells in Bone Marrow Transplant Model.

Interleukin (IL)-10-producing type 1 regulatory T (Tr1) cells, which are Foxp3memory T lymphocytes, play important roles in peripheral immune tolerance. We investigated whether Tr1 cells exert immunoregulatory effects in a mouse model of acute graft-versus-host disease (GVHD). Mouse CD4 T cells were induced to differentiate in vitro into Tr1 cells using vitamin D3 and dexamethasone, and these donor-derived Tr1 cells were infused on the day of bone marrow transplantation.

Robust Production of Cytomegalovirus pp65-Specific T Cells Using a Fully Automated IFN-γ Cytokine Capture System.

Background: Cytomegalovirus(CMV)-related diseases are a serious cause of morbidity and mortality following hematopoietic stem cell transplantation (HSCT). CMV-specific cytotoxic T lymphocytes (CMV-CTLs) have been reported as an alternative to antiviral drugs that provide long-term CMV-specific immunity without major side effects. However, their application has been limited by the prolonged manufacturing process required.

Infusions of Epstein-Barr virus-specific cytotoxic T lymphocytes as post-remission therapy in high-risk post-transplant lymphoproliferative disorder patients: report of two cases.

Conventional therapeutic approaches to post-transplant lymphoproliferative disorder (PTLD) occurring after solid-organ transplantation have shown only limited success in achieving durable response. Key factors driving the pathogenesis of PTLD include Epstein-Barr virus (EBV) reactivation and impaired immune surveillance due to prolonged immune suppression. Thus, EBV-specific cytotoxic T lymphocytes (EBV-CTLs) have emerged as an alternative therapeutic approach for the treatment of EBV-associated PTLD by enhancing EBV-specific immunity.

Third-party regulatory T cells prevent murine acute graft-versus-host disease.

Background/aims: Adoptive therapy with regulatory T (Treg) cells to prevent graft-versus-host disease (GVHD) would benefit from a strategy to improve homing to the sites of inflammation following hematopoietic stem cell transplantation (HSCT). Although donor-derived Treg cells have mainly been used in these models, third-party-derived Treg cells are a promising alternative for cell-based immunotherapy, as they can be screened for pathogens and cell activity, and banked for GVHD prevention. In this study, we explored major histocompatibility complex (MHC) disparities between Treg cells and conventional T cells in HSCT to evaluate the impact of these different cell populations on the prevention of acute GVHD, as well as survival after allogeneic transplantation.