Results 101 to 110 of about 16,862 (246)

VCP‐Regulated LMF2 Stabilizes the Cholesterol Biosynthesis Enzyme HMGCS1 to Drive Cancer Progression and Confer Capecitabine Resistance in Triple‐Negative Breast Cancer

open access: yesAdvanced Science, EarlyView.
LMF2 drives progression and capecitabine resistance in triple‐negative breast cancer (TNBC). Mechanistically, VCP prevents NBR1‐mediated autophagic degradation of LMF2, thereby stabilizing it. Stabilized LMF2 subsequently suppresses NDP52‐mediated autophagic degradation of HMGCS1, a rate‐limiting cholesterol biosynthesis enzyme.
Qian Zhao   +12 more
wiley   +1 more source

A thermodynamic assay to test pharmacological chaperones for Fabry disease.

open access: yesBiochim Biophys Acta, 2014
The majority of the disease-causing mutations affect protein stability, but not functional sites and are amenable, in principle, to be treated with pharmacological chaperones. These drugs enhance the thermodynamic stability of their targets. Fabry disease, a disorder caused by mutations in the gene encoding lysosomal alpha-galactosidase, represents an ...
Andreotti G   +3 more
europepmc   +5 more sources

Polyphosphate Copper Nanospheres Drive Mitochondrial Metabolic Reprogramming via Calcium Phase Separation for Self‐Sensitizing Cuproptosis

open access: yesAdvanced Science, EarlyView.
This study developed polyphosphate (polyP)‐based nanostructures that enable calcium‐mediated metabolic reprogramming via liquid–liquid phase separation (LLPS). Released polyP undergoes LLPS with Ca2+, suppressing glycolytic flux and enhancing mitochondrial metabolism effectively.
Jing Wang   +10 more
wiley   +1 more source

Hepatocyte CBX2 Safeguards Hepatic Lipid Homeostasis by Elevating Ca2+‐CaMKK2‐AMPK Signaling to Counter MASLD

open access: yesAdvanced Science, EarlyView.
In hepatocytes, CBX2 promotes H3K4me3 enrichment at the Orai1 promoter to enhance Orai1 transcriptional activation, thereby increasing intracellular Ca2+ levels. The elevated Ca2+ activates the CaMKK2‐AMPK signaling cascade, resulting in ACC phosphorylation and downstream metabolic regulation. This cascade suppresses de novo lipogenesis (Fasn, Acc, Scd‐
Xiang Wei   +18 more
wiley   +1 more source

Exploring the efficacy and safety of Ambroxol in Gaucher disease: an overview of clinical studies

open access: yesFrontiers in Pharmacology
Gaucher disease (GD) is mainly caused by glucocerebrosidase (GCase) enzyme deficiency due to genetic variations in the GBA1 gene leading to the toxic accumulation of sphingolipids in various organs, which causes symptoms such as anemia, thrombocytopenia,
Feda E. Mohamed   +4 more
doaj   +1 more source

CaMKIIδ Phosphorylates AUP1 to Promote Pancreatic Tissue Repair and Acinar‐to‐Ductal Metaplasia Formation via Mediating PERK‐Dependent Unfolded Protein Responses

open access: yesAdvanced Science, EarlyView.
CaMKIIδ–AUP1 signaling maintains PERK‐dependent ER homeostasis during ADM‐mediated pancreatic repair. ABSTRACT Pancreatic repair after acute pancreatitis (AP) is essential for restoring tissue integrity, but the intrinsic mechanisms coordinating acinar plasticity and regeneration remain poorly understood.
Yonghao Chen   +10 more
wiley   +1 more source

Harnessing ferroptosis from multilayer defense networks to nanoplatforms for specific cancer therapy

open access: yesBMEMat, EarlyView.
Nanomaterials target metabolically‐regulated ferroptosis for cancer therapy. Iron‐based or alternative nanoplatforms integrate ferroptosis with chemotherapy, immunotherapy, or radiotherapy. They enable stimulus‐responsive therapies (photothermal, photodynamic, sonodynamic) activated by near‐infrared, light, or ultrasound, achieving potent synergistic ...
Xinyue Xu   +5 more
wiley   +1 more source

AI-based discovery and cryoEM structural elucidation of a KATP channel pharmacochaperone

open access: yeseLife
Pancreatic KATP channel trafficking defects underlie congenital hyperinsulinism (CHI) cases unresponsive to the KATP channel opener diazoxide, the mainstay medical therapy for CHI. Current clinically used KATP channel inhibitors have been shown to act as
Assmaa Elsheikh   +7 more
doaj   +1 more source

Mitochondria‐endoplasmic reticulum organelle glue as maturation promoter for origination/dimensional dual‐cross cardiomyocytes

open access: yesBMEMat, EarlyView.
Mitochondria‐endoplasmic reticulum contact sites (MERCS) are areas where the mitochondria and endoplasmic reticulum closely interact. In this study, we utilize synthetic organelle glues to artificially engineer MERCS for regulating cardiomyocyte development, through which the immature and chemo‐plasticity issues of undifferentiated cells are addressed.
Wei Tang   +9 more
wiley   +1 more source

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