Results 91 to 100 of about 1,891 (215)

Phase I study of PF‐04895162, a Kv7 channel opener, reveals unexpected hepatotoxicity in healthy subjects, but not rats or monkeys: clinical evidence of disrupted bile acid homeostasis

open access: yesPharmacology Research & Perspectives, 2019
During a randomized Phase 1 clinical trial the drug candidate, PF‐04895162 (ICA‐105665), caused transaminase elevations (≥grade 1) in six of eight healthy subjects treated at 300 mg twice daily for 2‐weeks (NCT01691274). This was unexpected since studies
Michael D. Aleo   +10 more
doaj   +1 more source

Psychological Stress Associated Bile Acid Reprogramming Promotes Hepatocellular Carcinoma Progression

open access: yesAdvanced Science, EarlyView.
Depression is increasingly recognized as a risk factor for chronic diseases, yet its biological impact on cancer remains unclear. Using data from more than 490 000 participants across three international cohorts, we show that depression significantly increases the risk of liver cancer.
Ruijiang Zeng   +10 more
wiley   +1 more source

Bioengineered Exosome‐Loaded Immunomodulatory Bioadhesive Spray Reverses Liver Fibrosis and Metabolic Dysfunction That Triggers Beneficial Gut‐Liver Crosstalk in Chronic Fatty Liver Disease

open access: yesAdvanced Science, EarlyView.
Umbilical cord stem cell‐derived exosomes encapsulated in an immunomodulatory bioadhesive hydrogel spray enable localized therapy, sustained vesicle delivery, macrophage polarization, suppress systemic inflammation, and mitigate glucose and insulin homeostasis impairments in MAFLD.
Triya Saha   +4 more
wiley   +1 more source

Microalgae Hybrid Biosystem for Enhanced Oral Delivery of Rifaximin in Hepatic Encephalopathy Treatment

open access: yesAdvanced Science, EarlyView.
The microalgae‐nanoparticle hybrid system with antibacterial activity can improve the oral delivery and therapeutic efficiency for hepatic encephalopathy treatment. Oral administration of the system can reduced systemic ammonia levels, enhanced intestinal barrier function, attenuated systemic and neuroinflammation, ameliorated cognitive impairments ...
Kaiyue Wang   +8 more
wiley   +1 more source

Targeting GALNT7 Disrupts the TAZ O‐GalNAcylation Feedback Loop to Suppress Gallbladder Cancer Progression

open access: yesAdvanced Science, EarlyView.
Aberrant GALNT7‐mediated O‐GalNAcylation stabilizes TAZ to drive gallbladder cancer progression through a feed‐forward transcriptional loop. Structure‐based screening identifies Olaparib as a potent GALNT7 antagonist that disrupts this oncogenic axis, providing an immediate therapeutic strategy for this aggressive malignancy.
Peng Qiu   +11 more
wiley   +1 more source

Cobalt Single‐Atom Nanozyme for Enhanced Intestinal Radioprotection and Tumor Radiosensitization via Bidirectional ROS Modulation

open access: yesAdvanced Science, EarlyView.
Orally administered, pH‐responsive Co‐SAN exerts dual functions: in the alkaline intestinal milieu, it scavenges reactive oxygen species (ROS) and suppresses the PI3K/AKT pathway and NETs formation, thus providing radioprotection; whereas in the acidic tumor microenvironment, it generates ROS and alleviates hypoxia, thereby enhancing radiosensitization.
Shengqi Yin   +13 more
wiley   +1 more source

Mechanical Flexibility Enables DNA Origami to Overcome Steric Confinement in Mucus

open access: yesAdvanced Science, EarlyView.
Mechanical flexibility is introduced as a design parameter to enhance nanocarrier transport in mucus. Using DNA origami, flexibility is decoupled from size, shap and surface chemistry, revealing improved passage through confined hydrogel networks. While surface passivation reduces aggregation, flexibility further boosts transport, offering a general ...
Matteo Tollemeto   +5 more
wiley   +1 more source

HMGCR‐Driven Cholesterol Metabolism Promotes Osteoarthritis Progression by Accelerating Synovial Fibroblast Senescence

open access: yesAdvanced Science, EarlyView.
In the pathological context of osteoarthritis (OA), the phosphorylation of AKT1 at Ser473 enhances its binding to Lys140 of Insig1, which facilitates the formation of AKT1–Insig1 complex. Subsequently, the activation of AKT1 promotes the phosphorylation of Insig1 at Ser189, potentially enhancing the dissociation of Insig1 from sterol regulatory element‑
Xiaoqi Zhang   +19 more
wiley   +1 more source

Chemoselective Metabolomics via a Modular Reactivity‐Encoding Platform

open access: yesAdvanced Science, EarlyView.
Conventional LC–MS underrepresents numerous metabolites due to heterogeneous ionization efficiencies and matrix interference. Here, we introduce a modular reactivity‐encoding platform (MREP) comprising four alkyne‐tagged probes that selectively derivatize key functional groups, followed by unified click‐chemistry capture to eliminate matrix components ...
Xin Tao   +10 more
wiley   +1 more source

Oral Delivery Systems for Food‐Derived Bioactive Peptides: Enhancing Stability, Bioavailability, and Health Benefits

open access: yesAdvanced Science, EarlyView.
Advanced delivery systems—including nanoparticles, nanoemulsions, liposomes, and hydrogels—protect food‐derived bioactive peptides from gastrointestinal degradation and bitterness. These systems enable pH‐responsive release, enhance intestinal absorption, and improve therapeutic efficacy against oxidative stress, metabolic disorders, cancer, and ...
Yu Xu   +5 more
wiley   +1 more source

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