Pyogenic arthritis of the atlantoaxial joint is scarce. It can lead to several complications, such as spinal cord compression and cerebral vein thrombosis. A 51‐year‐old man presented with a twenty‐day history of inflammatory neck pain. Physical ...

Matrix metalloproteinases (MMPs) constitute a family of zinc-dependent endopeptidases that mediate extracellular matrix turnover and associated processes, such as cell survival, growth, and differentiation. This paper discusses important functions ...

Prostate cancer relies on genetic "switches," called enhancers, that can turn on tumor-promoting genes. Researchers at the University of Michigan Health Rogel Cancer Center have discovered histone H2B N-terminal acetylation (H2BNTac), an essential chemical mark of these enhancers.

Balassa et al. previously reported the outcomes of antiviral treatment for RSV lower respiratory tract infections in adults undergoing allogeneic haematopoietic cell transplantation (HCT).1 Profoundly...

Nitazoxanide (NTZ) is an FDA-approved anti-parasitic drug with broad-spectrum anti-infective, anti-inflammatory, and antineoplastic potential. However, its r...

Background and Objective: Reactive oxygen species (ROS) is a mediator of renal damage. Melatonin is a potent-free radical scavenger. Our objective was to test whether melatonin would protect against t...

Nature Reviews Drug Discovery - Tumour cells undergo profound changes in their metabolism, but targeting these metabolic pathways requires understanding of the impact on immune cells as well as...

The mechanisms by which opportunistic pathogens shift between commensalism and pathogenesis remains poorly understood. Here, the authors show that N-acetylglucosamine, a carbon source enriched in the ...

Patient A:II-1 was born in the Netherlands three weeks early with short, flattened bones in her upper body. She seemed otherwise healthy until her horseshoe-shaped kidneys began to fail.

Author summary Coxiella burnetii is a mammalian pathogen that can cause a predominantly zoonotic disease called Q-fever. In humans, Q-fever manifests as an acute or chronic illness especially in immun...

The novel coronavirus SARS-CoV-2 continues to cause death and disease throughout the world, underscoring the necessity of understanding the virus and host immune response. From the start of the pandem...

In hypoxic and inflamed tissues, oxygen (O2)-dependent antimicrobial defenses are impaired due to a shortage of O2. To gain insight into the mechanism…

Background Immune cell metabolism governs the outcome of immune responses and contributes to the development of autoimmunity by controlling lymphocyte pathogenic potential. In this study, we evaluated the metabolic profile of myelin-specific murine encephalitogenic T cells, to identify novel therapeutic targets for autoimmune neuroinflammation. Methods We performed metabolomics analysis on actively-proliferating encephalitogenic T cells to study their overall metabolic profile in comparison to resting T cells. Metabolomics, phosphoproteomics, in vitro functional assays, and in vivo studies in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS), were then implemented to evaluate the effect of metabolic targeting on autoreactive T cell pathogenicity. Finally, we confirmed the translational potential of our targeting approach in human pro-inflammatory T helper cell subsets and in T cells from MS patients. Results We found that autoreactive encephalitogenic T cells display an altered coenzyme A (CoA) synthesis pathway, compared to resting T cells. CoA fueling with the CoA precursor pantethine (PTTH) affected essential immune-related processes of myelin-specific T cells, such as cell proliferation, cytokine production, and cell adhesion, both in vitro and in vivo. Accordingly, pre-clinical treatment with PTTH before disease onset inhibited the development of EAE by limiting T cell pro-inflammatory potential in vivo. Importantly, PTTH also significantly ameliorated the disease course when administered after disease onset in a therapeutic setting. Finally, PTTH reduced pro-inflammatory cytokine production by human T helper 1 (Th1) and Th17 cells and by T cells from MS patients, confirming its translational potential. Conclusion Our data demonstrate that CoA fueling with PTTH in pro-inflammatory and autoreactive T cells may represent a novel therapeutic approach for the treatment of autoimmune neuroinflammation.

Immunotherapy utilizing tumor-infiltrating lymphocytes (TILs) is a promising approach for cancer treatment. Pentoxifylline (PTXF), a xanthine derivative, exhibits antitumor properties. This study aimed to investigate the impact of PTXF on the phenotype and function of TILs and splenocytes in a triple-negative breast cancer (TNBC) mouse model. TNBC was subcutaneously induced in BALB/c mice, followed by nine intraperitoneal injections of 100 mg/kg PTXF. TILs were then isolated by enzymatic digestion of tumors and cocultured with 4T1 cells. The proportion of regulatory T cells (Tregs) and cytotoxic T cells in TILs and splenocytes was assessed using flow cytometry. Transforming growth factor (TGF)-β and interferon (IFN)-γ production in TILs and splenocytes cultures was measured by ELISA. Relative expression of t-bet, foxp3, gata-3, and ror-γt in TILs and splenocytes was evaluated using real-time PCR. Tumor growth in PTXF-treated mice was significantly lower than that in the controls (P < 0.01). The frequency of regulatory and cytotoxic TILs in PTXF-treated mice was approximately half (P < 0.01) and twice (P < 0.05) that of the control group, respectively. The level of TGF-β and IFN-γ in the supernatant of PTXF-treated TILs was decreased and increased, respectively (P < 0.05). The relative expression of t-bet and foxp3 in the PTXF-treated mice compared to controls was increased and decreased, respectively (P < 0.05). Changes in the immune cell balance were less significant in the spleen compared to the TILs. PTXF treatment could limit the tumor growth and modify the regulatory-to-cytotoxic TILs ratio, as well as cytokine balance of TILs, in favor of antitumor responses.