Antibiotic resistance is a major problem, with methicillin-resistant Staphylococcus aureus (MRSA) being a prototypical example in surgical and community-acquired infections. S. aureus, like many pathogens, is immune evasive and able to multiply within host immune cells. Consequently, compounds that aid host immunity (e.g., by stimulating the host-mediated killing of pathogens) are appealing alternatives or adjuncts to classical antibiotics. Azithromycin is both an antibacterial and an immunomodulatory drug that accumulates in immune cells. We set out to improve the immunomodulatory properties of azithromycin by coupling the immune activators, nitric oxide and acetate, to its core structure. This new compound, designated CSY5669, enhanced the intracellular killing of MRSA by 45% ± 20% in monocyte-derived macrophages and by 55% ± 15% in peripheral blood leukocytes, compared with untreated controls. CSY5669-treated peripheral blood leukocytes produced fewer proinflammatory cytokines, while in both monocyte-derived macrophages and peripheral blood leukocytes, phagocytosis, ROS production, and degranulation were unaffected. In mice with MRSA pneumonia, CSY5669 treatment reduced inflammation, lung pathology and vascular leakage with doses as low as 0.01 μmol/kg p.o. CSY5669 had diminished direct antibacterial properties compared with azithromycin. Also, CSY5669 was immunomodulatory at concentrations well below 1% of the minimum inhibitory concentration, which would minimize selection for macrolide-resistant bacteria if it were to be used as a host-directed therapy. This study highlights the potential of CSY5669 as a possible adjunctive therapy in pneumonia caused by MRSA, as CSY5669 could enhance bacterial eradication while simultaneously limiting inflammation-associated pathology.
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http://dx.doi.org/10.1128/aac.02298-21 | DOI Listing |
Front Oncol
December 2024
Department of Hematology, Yeouido St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Introduction: Peripheral T-cell lymphomas (PTCLs) have poor outcomes in the relapsed/refractory (R/R) setting. In this study, we evaluated the efficacy of dexamethasone, L-asparaginase, ifosfamide, carboplatin, and etoposide (DL-ICE) chemotherapy followed by allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with R/R PTCLs.
Methods: We retrospectively analyzed 80 adult patients with R/R PTCLs treated with DL-ICE chemotherapy between September 2009 and March 2023.
Blood Sci
January 2025
State Key Laboratory of Experimental Hematology, National Clinical Research Center for Blood Diseases, Haihe Laboratory of Cell Ecosystem, PUMC Department of Stem Cell and Regenerative Medicine, CAMS Key Laboratory of Gene Therapy for Blood Diseases, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Tianjin 300020, China.
Irradiation with X-rays has been widely utilized in the clinical treatment of solid tumors and certain hematopoietic malignancies. However, this method fails to completely distinguish between malignant and normal cells. Prolonged or repeated exposure to radiation, whether due to occupational hazards or therapeutical interventions, can cause damage to normal tissues, particularly impacting the hematopoietic system.
View Article and Find Full Text PDFFront Cell Infect Microbiol
December 2024
Department of Infectious Diseases, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
Objective: The aim of this study was to assess the clinical value of metagenomic next-generation sequencing (mNGS) of blood samples for the identification of disseminated tuberculosis (DTB).
Methods: A total of 48 individuals suspected of DTB were enrolled. All patients underwent mNGS of peripheral blood and conventional microbiological tests.
Front Psychiatry
December 2024
West China Biomedical Big Data Center, West China Hospital, Sichuan University, Chengdu, China.
Background: Psychiatric illness is thought to be a brain somatic crosstalk disorder. However, the existing phenomenology-based Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnostic framework overlooks various dimensions other than symptoms. In this study, we investigated the associations between peripheral blood test indexes with various symptom levels of major depressive disorder (MDD), bipolar disorder (BD), and schizophrenia (SCZ) to explore the availability of peripheral blood test indexes.
View Article and Find Full Text PDFBioact Mater
March 2025
Department of Orthopedics and Rehabilitation, USA.
Osteoarthritis (OA) is a condition that affects the quality of life of millions of patients worldwide. Current clinical treatments, in most cases, lead to cartilage repair with deposition of fibrocartilage tissue, which is mechanically inferior and not as durable as hyaline cartilage tissue. We designed an mRNA delivery strategy to enhance the natural healing potential of autologous bone marrow aspirate concentrate (BMAC) for articular cartilage repair.
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