MF-59 (MF59)

Cellular interaction of mycosis fungoides tumor cells changes from cytotoxic CD8+ T cells in plaques to B cells in tumors.

Merkus Veerle A VA, IJsselsteijn Marieke E ME, Chevalier Marie S N MSN, de Haan Sanne S et al.

Mycosis Fungoides (MF) is characterized by the proliferation of malignant skin-homing memory CD4+ T cells. The disease typically follows an indolent course, progressing from plaques (scaly, erythematous skin lesions) in the early stages (Ia-Ib) to tumors (>IIb) in approximately one-third of cases. Although recent studies have explored cell phenotypes and counts of the tumor microenvironment (TME) in MF progression, spatial interactions between tumor and reactive cells remain poorly understood. We performed a comprehensive high-dimensional analysis of immune cell composition and cellular interactions across MF stages using a custom Imaging Mass Cytometry (IMC) panel to examine the spatial complexity of the MF TME. Stage-specific changes in the TME included an increased percentage of cytotoxic CD8+ cells in plaques and an increased percentage of B cells and dendritic cells in tumors. With progression of disease shift in the spatial organization of the TME was observed, from CD8+ T cell-tumor cell and monocyte-CD4+ T cell interactions in plaques to B cell-tumor cell interactions in tumors. A stage-dependent shift in interactions from anti-tumor immune responses to features consistent with immune evasion mechanisms has been observed with the progression of MF. These insights underscore the importance of spatial context in understanding MF progression and highlight therapeutic targets that could inform stage-specific (immune)therapies.

Guizhi Wuling Decoction alleviates myocardial fibrosis by restoring mitochondrial homeostasis: Evidence from network pharmacology, molecular docking, and multi-omics integration.

Shi Lipeng L, Wang Jie J, Yang Ruogu R, Qian Bingxin B et al.

Guizhi Wuling Decoction (GWD), a combined prescription consisting of the classical formulas Wuling San and Guizhi Fuling Wan without modification, has been clinically applied for cardiovascular diseases. Previous studies have reported its cardioprotective and anti-fibrotic effects; however, the underlying molecular mechanisms remain incompletely understood. To investigate whether restoration of mitochondrial homeostasis contributes to the anti-fibrotic effects of GWD and to explore the involvement of AMPK/PGC-1α signaling. Myocardial fibrosis (MF) was induced in C57BL/6 J mice by isoproterenol (ISO) administration. Cardiac function, myocardial fibrosis, mitochondrial ultrastructure, mitochondrial membrane potential, ATP production, and NAD+/NADH ratio were evaluated. Absorbed constituents in GWD-containing serum were characterized using UHPLC-MS/MS. Integrated transcriptomic-proteomic analysis highlighted AMPK signaling as one of the important pathways associated with GWD treatment. Molecular docking and molecular dynamics simulations were conducted to evaluate the interactions between representative absorbed compounds and candidate targets. The involvement of AMPK signaling was further validated by pharmacological inhibition using Compound C. GWD significantly improved cardiac function, attenuated myocardial fibrosis, and restored mitochondrial homeostasis, as evidenced by improved mitochondrial ultrastructure, increased mitochondrial membrane potential, ATP production, and NAD+/NADH ratio. Integrated transcriptomic and proteomic analyses identified AMPK signaling as an important pathway associated with the protective effects of GWD. Mechanistically, GWD activated the AMPK/PGC-1α signaling pathway and upregulated mitochondrial biogenesis- and quality control-related proteins, including NRF1, TFAM, and MFN2. Pharmacological inhibition of AMPK by Compound C significantly attenuated GWD-associated improvement of mitochondrial homeostasis and anti-fibrotic effects. GWD alleviates ISO-induced MF, at least in part, by restoring mitochondrial homeostasis. Integrated multi-omics analyses and pharmacological validation suggest that AMPK/PGC-1α signaling may contribute to the anti-fibrotic effects of GWD. These findings provide experimental evidence suggesting the involvement of mitochondrial homeostasis in MF and offer new insights into the anti-fibrotic effects of GWD.

[Senegalese experience with volumetric modulated arc therapy in the treatment of locally advanced rectal adenocarcinoma: a retrospective study of 59 cases].

Ka Kanta K, Dieng Mamadou Moustapha MM, Edimo Lionel Eric Francis LEF, Ndong Boucar B et al.

Isolation of a Bridging Phosphide-Supported Redox-Active Neutral Ag4-Nanocluster as a Molecular Energy Storage Material.

Vikas Nivedya K NK, Thosare Mayur M, Hossain Sayed Imroz SI, Purushothaman Akshara A et al.

Stabilization of robust and structurally well-defined AgI-based nanoclusters as molecular pseudocapacitors for electrochemical energy storage has been unexplored. Herein, we report on the novel synthesis, solid-state isolation, and pseudocapacitor studies of an atomically precise neutral redox-active Ag4 nanocluster [((Cy-cAI)P(Dipp))4Ag4] (2), supported by the unique bulky μ2-phosphide ligands. Cyclic voltammetry (CV) studies on 2 revealed a possible quasi-reversible one-electron reduction, suggesting in situ generation of the corresponding radical anion 2·-, which was further supported by the electron paramagnetic resonance (EPR) spectroscopy and Mulliken spin density calculations. The unprecedented effort to fabricate an electrode by depositing 2 on a solid support, investigating the pseudocapacitive behavior in a 1 M NaClO4 electrolyte by employing a three-electrode cell arrangement, was successful. The corresponding CV profiles exhibited a quasi-rectangular profile with redox peaks, signifying a combination of electric double-layer capacitive (EDLC) and pseudocapacitive effects with the highest specific capacitance value of 168.9 F g-1 (185.8 mF cm-2) at a 2 mV s-1 scan rate.