Cellular events in the spleen during the development of acute GvH reaction in lethally irradiated recipients of allogeneic lymphocytes may be divided into 6 interrelated processes: (1) entering and lodging in the spleen of about 17% of inoculated cells which forms the compartment of potentially reactive cells; (2) transformation (recruitment) of about 30% of cells lodged in the spleen into large pyroninophilic cells (LPC), a process lasting about 12-16 hr; (3) proliferation of recruited LPC by five successive divisions with a Tc of about 12 hr; (4) transformation of LPC into non-LPC; (5) proliferation of non-LPC by one division, with a Tc of about 8 hr; and (6) migration of mature immunologically active cells from the spleen. The last process correlates well with the concomitant appearance of lymphocytes in the peripheral blood (killer cells) and with the time of acute death among inoculated mice.
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Brain
January 2025
Institute of Neurological Sciences and Psychiatry, Hacettepe University, 06100, Ankara, Turkey.
Cortical spreading depolarization (CSD), the neurophysiological event believed to underlie aura, may trigger migraine headaches through inflammatory signaling that originates in neurons and spreads to the meninges via astrocytes. Increasing evidence from studies on rodents and migraine patients supports this hypothesis. The transition from pro-inflammatory to anti-inflammatory mechanisms is crucial for resolving inflammation.
View Article and Find Full Text PDFPLoS Pathog
January 2025
Integrative Cell Biology Graduate Program, Loyola University Chicago, Maywood, Illinois, United States of America.
The early stages of HIV-1 infection include the trafficking of the viral core into the nucleus of infected cells. However, much remains to be understood about how HIV-1 accomplishes nuclear import and the consequences of the import pathways utilized on nuclear events. The host factor cleavage and polyadenylation specificity factor 6 (CPSF6) assists HIV-1 nuclear localization and post-entry integration targeting.
View Article and Find Full Text PDFPLoS Pathog
January 2025
Institute of Pediatric Infection, Immunity, and Critical Care Medicine, Shanghai Children's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
IKKε is a traditional antiviral kinase known for positively regulating the production of type I interferon (IFN) and the expression of IFN-stimulated genes (ISGs) during various virus infections. However, through an inhibitor screen targeting cellular kinases, we found that IKKε plays a crucial role in the lytic replication of Kaposi's sarcoma-associated herpesvirus (KSHV). Mechanistically, during KSHV lytic replication, IKKε undergoes significant SUMOylation at both Lys321 and Lys549 by the viral SUMO E3 ligase ORF45.
View Article and Find Full Text PDFAdv Sci (Weinh)
January 2025
School of Laboratory Medicine and Biotechnology, Southern Medical University, Guangzhou, 510515, China.
Despite substantial advances in the antitumor effects of annonaceous acetogenins (ACGs), the absence of a defined biological action mechanism remains a major barrier to their clinical application. Here, it is found that squamocin effectively depletes both EZH2 and MYC in multiple cancer cell lines, including head and neck squamous cell carcinoma, and gastric and colorectal cancer, demonstrating potent efficacy in suppressing these in vivo tumor models. Through the combination of surface plasmon resonance (SPR), differential scanning fluorimetry (DSF), and cellular thermal shift assay (CETSA), heat shock protein 90α (HSP90α) is identified as the direct binding target of squamocin.
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