Early Hyperprogression of Rhabdomyosarcoma Detected by 18 F-FDG PET/CT Three Weeks after CAR-T Treatment.

Chimeric antigen receptor T-cell (CAR-T) treatment has been widely used in the treatment of hematological malignancies, and its application has been gradually expanded to the research and treatment of solid tumors. However, unconventional types of response may occur after CAR-T treatment, such as hyperprogression, resulting in terrible outcomes. Here, we report the case of a 13-year-old adolescent boy with relapsed and refractory rhabdomyosarcoma who developed early hyperprogression 3 weeks after CAR-T treatment (target: B7H3 and CD171), which was detected by fluorine-18 fluorodeoxyglucose ( 18 F-FDG) positron emission tomography (PET)/computed tomography (CT). The patient eventually underwent amputation. Attention should be paid to the possibility of early hyperprogression after CAR-T treatment, and 18 F-FDG PET/CT has an absolute advantage in early evaluating treatment response to immunotherapy.

Nicotine Activating α4ß2 Nicotinic Acetylcholine Receptors to Suppress Neuroinflammation via JAK2-STAT3 Signaling Pathway in Ischemic Rats and Inflammatory Cells.

Nicotine plays a role in inhibiting inflammatory factors, which contributes to improving cognitive impairment by activating α4ß2 nAChRs in ischemic rats, but the underlying mechanism has not been fully elucidated. Janus tyrosine kinase 2-signal transducer and activator of transcription 3 (JAK2-STAT3) signaling pathway is involved in cognitive improvement, and there seems to be a relationship between nAChRs and JAK2-STAT3 as well. The aim of this study is to explore the role of JAK2-STAT3 signaling pathway in nicotine-mediated anti-inflammatory effect. Nicotine, DHßE (the strongest competitive antagonist of α4ß2 nAChRs), and AG490 (a specific JAK2-STAT3 blocker) were used to intervene and treat ischemic rats and HEK-293 T-hα4ß2 cells. The Morris water maze (MWM) test and 2-[18F]-A-85380 PET imaging were performed to detect the cognitive function and α4ß2 nAChRs density in ischemic rats. The results demonstrated that nicotine intervention increased the density of α4ß2 nAChRs and improved cognitive impairment, but this effect was blocked by AG490, and the receptors were still upregulated. Essentially, when the JAK2-STAT3 signaling pathway was blocked, nicotine could only upregulate the expression of α4ß2 nAChRs, but not improve the cognitive function. PCR and Western blot analysis further confirmed these results. The cell experiments also showed that nicotine could reduce inflammatory factors stimulated by LPS and upregulate the expression of pJAK2 and pSTAT3 in HEK-293 T-hα4ß2 cells, while AG490 and DHßE reversed the effect of nicotine. To sum up, our work indicated that JAK2-STAT3 signaling pathway played an important role in nicotine-induced cognitive improvement by upregulating α4ß2 nAChRs in ischemic rats.

Microglia Polarization From M1 to M2 in Neurodegenerative Diseases.

Microglia-mediated neuroinflammation is a common feature of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Microglia can be categorized into two opposite types: classical (M1) or alternative (M2), though there's a continuum of different intermediate phenotypes between M1 and M2, and microglia can transit from one phenotype to another. M1 microglia release inflammatory mediators and induce inflammation and neurotoxicity, while M2 microglia release anti-inflammatory mediators and induce anti-inflammatory and neuroprotectivity. Microglia-mediated neuroinflammation is considered as a double-edged sword, performing both harmful and helpful effects in neurodegenerative diseases. Previous studies showed that balancing microglia M1/M2 polarization had a promising therapeutic prospect in neurodegenerative diseases. We suggest that shifting microglia from M1 to M2 may be significant and we focus on the modulation of microglia polarization from M1 to M2, especially by important signal pathways, in neurodegenerative diseases.