sirolimus

TCM-derived compounds exert multifaceted neuroprotective and psychotropic effects, while successful clinical translation requires strengthened pharmaceutical characterization, standardized dosing strategies and advanced delivery systems such as nanoformulations, phytosomes and standardized granules to enhance bioavailability, reliability and regulatory acceptance.

The key pathways implicated include mTOR (mechanistic target of rapamycin), NF-kappaB (nuclear factor kappa-light-chain-enhancer of activated B cells), and JAK/STAT (Janus kinase-signal transducer and activator of transcription), which together shape cytokine release, T-cell responsiveness, macrophage function, and natural killer cell-mediated cytotoxicity...Understanding how anesthetic techniques shape perioperative immunity offers an opportunity to refine anesthetic decision-making and develop evidence-based strategies aimed at improving short- and long-term patient outcomes. This article aims to review the effect of anesthetic techniques and medications on the immune response during the perioperative period.

In a castrated PC-3 xenograft model, PLP (400 mg/kg/day) suppressed tumor volume growth by 91.7% and tumor weight growth by 78.0% compared with the control group, showing efficacy comparable to abiraterone/prednisone without hepatorenal toxicity...Integrative transcriptomic and multi-omics analyses revealed coordinated downregulation of phosphatidylinositol 3-kinase-protein kinase B-mechanistic target of rapamycin signaling and upregulation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). Functional validation showed that overexpression of phosphoinositide-3-kinase regulatory subunit 1 rescued PLP-induced tumor suppression, whereas knockdown of PGC-1α abolished its antioxidative and antiproliferative effects, indicating that both pathways are critically involved. These findings suggest that PLP combats CRPC by simultaneously inhibiting oncogenic signaling and mitigating oxidative stress, positioning it as a promising natural therapeutic candidate for CRPC.

The patient was treated with VAC chemotherapy (vincristine, actinomycin D, cyclophosphamide), local radiotherapy (60 Gy), cranial prophylactic radiotherapy (12 Gy), and subsequent debulking surgery. Multimodal treatment incorporating chemotherapy, radiotherapy, surgery, and targeted maintenance therapy can achieve meaningful disease control in aggressive craniofacial MCS. To our knowledge, this represents one of the very few reported pediatric cases of maxillary MCS with confirmed HEY1::NCOA2 fusion managed with sirolimus-based maintenance therapy.

Loss of ipmk-1 causes excessive ER calcium retention, leading to compromised mitochondrial bioenergetic capacity and reduced activity of the C. elegans target of rapamycin (ceTOR) pathway...This multiple-pathway architecture underscores the evolutionary conservation of IPMK as a nexus that integrates nutrient sensing and processing, calcium signaling, and organismal aging. Further research on these functions and their underlying mechanisms of IPMK could help to understand IPMK mediated human metabolic and age-related disorders.

P1/2, N=54, Suspended, National Cancer Institute (NCI) | Recruiting --> Suspended

P2, N=65, Not yet recruiting, Rapa Therapeutics LLC | Trial completion date: Sep 2028 --> Sep 2029 | Trial primary completion date: Mar 2028 --> Mar 2029

Notably, repurposed drugs exhibit anticancer activity by modulating key pathways, including phosphatidylinositol 3-kinase/Ak strain transforming/mechanistic target of rapamycin, mitogen-activated protein kinase/extracellular signal-regulated kinase, wingless-related integration site/β-catenin signaling, as well as redox homeostasis and DNA response...With cancer causing one in six global deaths and marked by therapeutic resistance and molecular heterogeneity, drug repurposing provides a scalable solution. This approach bridged preclinical insight with clinical application, potentially transforming cancer therapeutics through rational, data-driven innovation.

The involvement of the mTOR pathway was further examined by combining MCCC2 knockdown with rapamycin treatment and leucine-deprivation experiments...MCCC2 promotes TNBC progression by activating the mTOR signaling pathway in a leucine-dependent manner. Targeting MCCC2 and its metabolic axis may represent a promising therapeutic strategy for TNBC.

Sequestosome 1 (SQSTM1)/p62, which functions as a signaling hub integrating nuclear factor kappa B (NF-κB), the mechanistic target of rapamycin complex 1 (mTORC1), and Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (NRF2) pathways, serves as a selective macroautophagy/autophagy receptor that binds ubiquitinated cargo proteins and recruits them to the autophagosome for subsequent degradation in the autolysosome. Furthermore, the phase separation of p62 is an important regulatory process in the autophagy mechanism, but recent studies have demonstrated that impaired or excessive autophagy mediated by p62 is associated with cancer development. This review summarizes the role of autophagy-including its types, mechanisms, and the pathway related to the ubiquitin-dependent selective autophagy receptor p62-in cancer progression.

The Phosphoinositide 3-kinase (PI3K), Protein kinase B (AKT) and mechanistic target of rapamycin (mTOR) pathway has been documented to regulate MPMCA-inhibited cell motility...Importantly, our in vivo data indicates that MPMCA reduces Snail and Slug expression and prostate cancer metastasis. Our evidence suggests that MPMCA is a novel therapeutic candidate for treating metastatic prostate cancer.

High CD44 expression was associated with advanced disease, immune cell infiltration, immune checkpoint gene expression, reduced sensitivity to gemcitabine, paclitaxel, rapamycin, and FMK, and distinct CTLA4/PD-L1 checkpoint profiles. CD44 exhibits compartment-specific regulation in PDAC, linking immune remodeling, exosome signaling, and therapeutic resistance to adverse clinical outcome.