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Costimulation blockade: the next generation.
Curr Opin Organ Transplant
January 2025
Division of Nephrology, Virginia Commonwealth University, Richmond, Virginia, USA.
Purpose Of The Review: Calcineurin inhibitors (CNIs) are central to immunosuppression in kidney transplantation (KT), improving short-term outcomes but falling short in enhancing long-term outcomes due to cardiovascular, metabolic, and renal complications. Belatacept, an FDA-approved costimulation blocker, offers a less toxic alternative to CNIs but is limited by its intravenous administration and reduced efficacy in high-immunological-risk patients.
Recent Findings: Emerging therapies target more specific pathways to improve efficacy and accessibility.
Update on the evolving landscape of pneumococcal capsule types: new discoveries and way forward.
Clin Microbiol Rev
January 2025
Department of Medicine, Division of Pulmonary/Allergy/Critical Care, The University of Alabama at Birmingham, Birmingham, Alabama, USA.
SUMMARY (the "pneumococcus") is a significant human pathogen. The key determinant of pneumococcal fitness and virulence is its ability to produce a protective polysaccharide (PS) capsule, and anti-capsule antibodies mediate serotype-specific opsonophagocytic killing of bacteria. Notably, immunization with pneumococcal conjugate vaccines (PCVs) has effectively reduced the burden of disease caused by serotypes included in vaccines but has also spurred a relative upsurge in the prevalence of non-vaccine serotypes.
View Article and Find Full Text PDFEarly transcriptomic changes at the skin interface during Powassan virus transmission by ticks.
Front Immunol
January 2025
Department of Microbiology and Immunology, State University of New York Upstate Medical University, Syracuse, NY, United States.
Introduction: Powassan virus (POWV), a vector-borne pathogen transmitted by ticks in North America, is the causative agent of Powassan encephalitis. As obligate hematophagous organisms, ticks transmit pathogens like POWV at the tick bite site, specifically during the initial stages of feeding. Tick feeding and salivary factors modulate the host's immunological responses, facilitating blood feeding and pathogen transmission.
View Article and Find Full Text PDFThe polymerase gamma (POLG) gene mutation is associated with mitochondria and metabolism disorders, resulting in heterogeneous responses to immunological activation and posing challenges for mitochondrial disease therapy. Optical metabolic imaging captures the autofluorescent signal of two coenzymes, NADH and FAD, and offers a label-free approach to detect cellular metabolic phenotypes, track mitochondria morphology, and quantify metabolic heterogeneity. In this study, fluorescence lifetime imaging (FLIM) of NAD(P)H and FAD revealed that POLG mutator macrophages exhibit a decreased NAD(P)H lifetime, and optical redox ratio compared to the wild-type macrophages, indicating an increased dependence on glycolysis.
View Article and Find Full Text PDFRoads to remission: evolving treatment concepts in type 2 inflammatory diseases.
EClinicalMedicine
February 2025
Institute of Laboratory Medicine and Pathobiochemistry, Molecular Diagnostics, Philipps University Marburg, Marburg, Germany.
Unlabelled: Non-communicable diseases (NCDs) characterised by type 2 inflammation, including asthma, allergic rhinitis, chronic rhinosinusitis with nasal polyps, atopic dermatitis, food allergies and eosinophilic esophagitis, are increasing in prevalence worldwide. Currently, there is a major paradigm shift in the management of these diseases, towards the concept of disease modification and the treatment goal remission, regardless of severity and age. Remission as a treatment goal in chronic inflammatory NCDs was first introduced in rheumatoid arthritis, and then adopted in other non-type 2 inflammatory diseases.
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