The manuscript investigated the isolation, characterization and anti-infective potential of valinomycin (), streptodepsipeptide P11A (), streptodepsipeptide P11B (), and one novel valinomycin analogue, streptodepsipeptide SV21 (), which were all produced by the Gram-positive strain SV 21. Although the exact molecular weight and major molecular fragments were recently reported for compound , its structure elucidation was not based on compound isolation and spectroscopic techniques. We successfully isolated and elucidated the structure based on the MS fragmentation pathways as well as H and C NMR spectra and found that the previously reported structure of compound differs from our analysis. Our findings showed the importance of isolation and structure elucidation of bacterial compounds in the era of fast omics technologies. The here performed anti-infective assays showed moderate to potent activity against fungi, multi drug resistant (MDR) bacteria and infectivity of the Hepatitis C Virus (HCV). While compounds , and revealed potent antiviral activity, the observed minor cytotoxicity needs further investigation. Furthermore, the here performed anti-infective assays disclosed that the symmetry of the valinomycin molecule is most important for its bioactivity, a fact that has not been reported so far.
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http://dx.doi.org/10.3390/md19020081 | DOI Listing |
Neurology
February 2025
Department of Neurology and Center of Clinical Neuroscience, First Medical Faculty, General University Hospital and Charles University, Prague, Czech Republic.
Background And Objectives: Patients with multiple sclerosis (MS) may demonstrate better disease control when treatment is initiated on high-efficacy disease-modifying therapies (DMTs) from onset. This subgroup analysis assessed the long-term efficacy and safety profile of the high-efficacy DMT ocrelizumab (OCR) as first-line therapy for early-stage relapsing MS (RMS).
Methods: Post hoc exploratory analyses of efficacy and safety were performed in a subgroup of treatment-naive patients with RMS who received ≥1 dose of OCR in the multicenter OPERA I/II (NCT01247324/NCT01412333) studies.
Proc Natl Acad Sci U S A
February 2025
State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou 510050, China.
Chromobox 2 (CBX2), a crucial component of the polycomb repressive complex (PRC), has been implicated in the development of various human cancers. However, its role in the regulation of tumor immunogenicity and immune evasion remains inadequately understood. In this study, we found that ablation of CBX2 led to tumor growth inhibition, activation of the tumor immune microenvironment, and enhanced therapeutic efficacy of anti-PD1 or adoptive T cell therapies by using murine syngeneic tumor models.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
February 2025
U.S. Military HIV Research Program, Center for Infectious Disease Research, Walter Reed Army Institute of Research, Silver Spring, MD 20910.
HIV-1 envelope broadly neutralizing antibodies represent a promising component of HIV-1 cure strategies. To evaluate the therapeutic efficacy of combination monoclonal antibodies (mAbs) in a rigorous nonhuman primate model, we tested different combinations of simian immunodeficiency virus (SIV) neutralizing mAbs in SIVmac251-infected rhesus macaques. Antiretroviral therapy-suppressed animals received anti-SIV mAbs targeting multiple Env epitopes spanning analytical treatment interruption (ATI) in 3 groups (n = 7 each): i) no mAb; ii) 4-mAb combination; and iii) 2-mAb combination.
View Article and Find Full Text PDFPLoS One
January 2025
Cell Therapy Center, The University of Jordan, Amman, Jordan.
Background: Hypoxia in tumor cells is linked to increased drug resistance and more aggressive behavior. In pancreatic cancer, the tumor microenvironment is notably hypoxic and exhibits strong immunosuppressive properties. Given that immunotherapy is now approved for pancreatic cancer treatment, further understanding of how pancreatic tumor cell hypoxia influences T-cell cytotoxicityis essential.
View Article and Find Full Text PDFJ Chem Inf Model
January 2025
Schrödinger Incorporated, Cambridge, Massachusetts 02142, United States.
Accurate prediction of the affinity of ligand binding to nucleic acids represents a formidable challenge for current computational approaches. This limitation has hindered the use of computational methods to develop small-molecule drugs that modulate the activity of nucleic acids, including those associated with anticancer, antiviral, and antibacterial effects. In recent years, significant scientific and technological advances as well as easier access to compute resources have contributed to free-energy perturbation (FEP) becoming one of the most consistently reliable approaches for predicting relative binding affinities of ligands to proteins.
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