Results 51 to 60 of about 65,616 (261)

Microglial Deubiquitinase OTUD7B Stabilizes STAT3 to Promote Neuroinflammation and Cognitive Decline in Alzheimer's Disease

open access: yesAdvanced Science, EarlyView.
. ABSTRACT Neuroinflammation driven by microglial activation is a defining feature of Alzheimer's disease (AD), yet the molecular mechanisms sustaining this proinflammatory state remain unclear. Here, we identify the deubiquitinase OTUD7B as a critical regulator of microglial activation and AD pathology.
Luyao Li   +15 more
wiley   +1 more source

Astrocytic Phenotypic Switching in Posterior Piriform Cortex Orchestrates Bone Cancer Pain–Depression Comorbidity via Purinergic–Noradrenergic Signaling

open access: yesAdvanced Science, EarlyView.
Bone cancer pain and depression share a common origin: astrocytic A2‐to‐A1 transition in the posterior piriform cortex. This phenotypic shift disrupts the ATP–adenosine–A2AR–norepinephrine axis, simultaneously driving nociceptive and affective dysfunction.
Jiang‐Ping Liu   +14 more
wiley   +1 more source

VDAC1 Upregulation Induces Hyperexcitability of Nociceptive Sensory Neurons Via Enhanced Mitochondrial Atp Efflux in Neuropathic Pain

open access: yesAdvanced Science, EarlyView.
The mechanism diagram of VDAC1 mediating neuronal excitability and neuropathic pain. Briefly, VDAC1 is expressed in DRG neurons and is upregulated following CCI‐induced neuropathic pain. This upregulation enhances ATP transport from mitochondria to the cytoplasm in sensory neurons, leading to increased neuronal excitability and pain behavior.
Fengrun Sun   +7 more
wiley   +1 more source

In Vivo Gene Editing of Muscle Stem Cells with Adeno-Associated Viral Vectors in a Mouse Model of Duchenne Muscular Dystrophy

open access: yesMolecular Therapy: Methods & Clinical Development, 2020
Delivery of therapeutic transgenes with adeno-associated viral (AAV) vectors for treatment of myopathies has yielded encouraging results in animal models and early clinical studies.
Jennifer B. Kwon   +7 more
doaj   +1 more source

TOLLIP Inhibits Psoriasis Progression via Suppressing PKM2‐Mediated Glycolysis in Keratinocytes

open access: yesAdvanced Science, EarlyView.
In this study, we identify TOLLIP as a critical regulator of psoriasis pathogenesis through its modulation of glycolytic metabolism. Our findings establish the TOLLIP‐PKM2‐glycolysis axis as a key mechanism linking metabolic reprogramming to psoriasis pathogenesis, and propose TOLLIP as a promising therapeutic target.
Xiuhuan Jiang   +11 more
wiley   +1 more source

Cross-Packaging and Capsid Mosaic Formation in Multiplexed AAV Libraries

open access: yesMolecular Therapy: Methods & Clinical Development, 2020
Generation and screening of libraries of adeno-associated virus (AAV) variants have emerged as a powerful method for identifying novel capsids for gene therapy applications.
Pauline F. Schmit   +13 more
doaj   +1 more source

BIN1 and ALDH1B1 Deficiency in Colonic Smooth Muscle Drives Mitochondrial Dysfunction and Fibrosis in Slow‐Transit Constipation

open access: yesAdvanced Science, EarlyView.
Slow‐transit constipation (STC) is a disabling motility disorder with unclear smooth‐muscle mechanisms. Spatial proteomic analysis of STC patient colon reveals both the central pathogenic role of smooth muscle cells (SMCs) in STC and novel regulators of intestinal motility, BIN1 and ALDH1B1.
Jianbo Liu   +10 more
wiley   +1 more source

Palatable‐Food–Driven Top‐Down Circuit Inhibits PVNCRF Activity to Mitigate Stress Via Peri‐PVNCRFR1 Neurons

open access: yesAdvanced Science, EarlyView.
Palatable food alleviates stress and prevents anxiety. This study uncovers a dedicated neural pathway: dopamine release in the PFC activates D1R neurons, whose projections to the peri‐PVN engage a population of anxiolytic CRFR1 neurons. These neurons then inhibit stress‐induced hyperactivity of PVNCRF neurons, providing a circuit‐level explanation for ...
Yuchuan Hong   +12 more
wiley   +1 more source

Macrophage‐to‐Myofibroblast Transdifferentiation Contributes to Pulmonary Fibrosis via the MERTK‐SPP1‐SRC‐TKS5 Signaling Axis

open access: yesAdvanced Science, EarlyView.
MERTK is upregulated in fibrotic macrophages and regulates the expression and activity of SRC and TKS5 through SPP1, mediating transdifferentiation of macrophages‐to‐myofibroblasts (MMT) and promoting pulmonary fibrosis. The figure was created with BioRender.com.
Yungeng Wei   +3 more
wiley   +1 more source

A Generic Method for Fast and Sensitive Detection of Adeno-Associated Viruses Using Modified AAV Receptor Recombinant Proteins

open access: yesMolecules, 2019
Adeno-Associated Viruses (AAV) are widely used gene-therapy vectors for both clinical applications and laboratory investigations. The titering of different AAV preparations is important for quality control purposes, as well as in comparative studies ...
Mengtian Cui   +7 more
doaj   +1 more source

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