sirolimus

Abbreviations: AAV: adeno-associated virus; ACTB/β-actin: actin, beta; AIF1/IBA1: allograft inflammatory factor 1; BAF: bafilomycin A1; BNIP3: BCL2/adenovirus E1B interacting protein 3; CCI: controlled cortical impact; COX8: cytochrome c oxidase subunit 8; CUT&Tag: cleavage under targets and tagmentation; DAPI: 4,'6-diamidino-2-phenylindole; DEGs: differentially expressed genes; eGFP: enhanced green fluorescent protein; EGR1: early growth response 1; GFAP: glial fibrillary acidic protein; GO: gene ontology; GSEA: gene set enrichment analysis; HCQ: hydroxychloroquine; HIF1A/HIF-1α: hypoxia inducible factor 1, alpha subunit; IGV: integrative genomics viewer; KEGG: Kyoto encyclopedia of genes and genomes; KO: knockout; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; Lv: lentivirus; MAP2: microtubule-associated protein 2; mCherry: monomeric cherry fluorescent protein; mRFP: monomeric red fluorescent protein; MTOR: mechanistic target of rapamycin kinase; MUT: mutant; MWM: Morris water maze; NAB1: Ngfi-A binding protein 1; NAB2: Ngfi-A binding protein 2; RBFOX3/NeuN: RNA binding protein, fox-1 homolog (C. elegans) 3; OGD: oxygen-glucose deprivation; OLIG2: oligodendrocyte transcription factor 2; PBS: phosphate-buffered saline; PECAM1/CD31: platelet/endothelial cell adhesion molecule 1; PFA: paraformaldehyde; PPI: protein-protein interaction; Puro: puromycin; ROI: region of interest; ROS: reactive oxygen species; SEM: standard error of the mean; SQSTM1/p62: sequestosome 1; TBI: traumatic brain injury; TOMM20: translocase of outer mitochondrial membrane 20; TSA: tyramide signal amplification; TUNEL: terminal deoxynucleotidyl transferase dUTP nick end labeling; VDAC1: voltage-dependent anion channel 1; WT: wild-type.

Such combined treatment showed promising synergistic interaction via several molecular pathways, which is well tolerated and readily applicable strategy to improve the therapeutic outcome of PDT in cancer cell treatment.

The mechanistic target of rapamycin complex 2 (mTORC2), a key regulator of cellular metabolism, growth, and survival, remains poorly characterized in the context of dopaminergic neurotoxicity...Genetic inactivation of mTORC2 reduced basal phosphorylation of the cellular energy sensor AMP-activated protein kinase (AMPK), but did not alter neurotoxin-induced phosphorylation of AMPK or the mitogen-activated protein kinases ERK and JNK. Together, these findings demonstrate a protective role of mTORC2 components against 6-OHDA-induced, and to a lesser extent, MPP+-induced, mitochondrial damage and apoptotic cell death.

Neuronal and oligodendroglial firing activates ADAM10, generating soluble NLGN3 (sNLGN3) that reprograms glioma cells toward a highly neural, synapse-competent state through kinase, epigenetic and mechanosensory pathways, including LYN proto-oncogene, Src family tyrosine kinase (LYN), phosphoinositide 3-kinase (PI3K)-mechanistic target of rapamycin (mTOR) and chondroitin sulfate proteoglycan 4 (CSPG4)-Piezo-type mechanosensitive ion channel component 1 (PIEZO1) signaling...On this basis, we outline an "actionable circuit" spanning neuronal activity, NLGN3-ADAM10 shedding, intracellular signaling, synaptic integration and network remodeling, and we organize emerging pharmacologic and device-based strategies into a circuit-breaking framework that includes activity dampening, inhibition of NLGN3 shedding, blockade of downstream signaling and AMPA synapses, and network-level modulation. Finally, we highlight key translational challenges and opportunities in target selectivity, brain delivery, biomarker development and adaptive trial design, arguing that multidimensional, circuit-informed interventions may complement standard surgery, radiochemotherapy and molecular targeting in selected patients with activity-driven glioma.

P1, N=45, Recruiting, Barinthus Biotherapeutics | Trial completion date: Jun 2026 --> Nov 2026 | Trial primary completion date: Jun 2026 --> Nov 2026

In vivo, Sch C markedly reduced tumor volume and weight without obvious toxicity and increased apoptosis while decreasing proliferation in tumor tissues. Sch C exerts antimelanoma effects and is associated with inhibition of PI3K/AKT/mTOR signaling and modulation of Rap1-related pathways, suggesting its potential as a therapeutic candidate for melanoma.

P1/2, N=20, Not yet recruiting, Oslo University Hospital HF

Puerarin halted the malignant progression of CRC by reprogramming tumor lipid metabolism. Puerarin thus hold promise as a clinically deployable lipid-centric agent that could synergistically potentiate conventional anticancer drugs.

More importantly, administering rapamycin, a potent inhibitor of oligodendrogenesis, during repeated fear recalls phenocopies the effects of anti-myelination on fear memory-related behavioral defects...Pharmacological treatments that inhibiting oligodendrogenesis during the recall phase represent a promising therapeutic strategy for preventing the pathological reinforcement of long-term fear memories, thereby averting the emergence of anxiety-like behaviors and social preference deficits in individuals with PTSD. Schematic image summarizing the major findings of the present study.

The underlying mechanism of this phenomenon was associated with the modulation of autophagic pathways by rapamycin, encouraging the differentiation of naïve CD4 T cells into MOG35-55-specific Tregs, as evidenced by tetramer staining. These findings provide a conceptual framework for exploring strategies aimed at promoting antigen-specific tolerance in autoimmune diseases.

This study highlights the need for further investigation into the efficacy of pathway inhibitors in managing TSC-related lipomas in vivo and offers a potential treatment avenue for patients suffering from recurrent lipomatosis.

P2, N=6, Active, not recruiting, M.D. Anderson Cancer Center | Recruiting --> Active, not recruiting | Trial primary completion date: Jun 2026 --> Jun 2028