Exercise-induced irisin ameliorates cognitive impairment following chronic cerebral hypoperfusion by suppressing neuroinflammation and hippocampal neuronal apoptosis.

Background: Chronic cerebral hypoperfusion (CCH) is a pathophysiological hallmark of vascular dementia, the second most common form of dementia. CCH exerts complex and subtle detrimental effects on both the brain and peripheral systems. Irisin is a polypeptide primarily expressed in contracting skeletal muscle and the brain.

Identification and Protective Strategies for "Cortical Dangerous Veins" in Neurosurgical Craniotomies.

Objective: To investigate the identification and management techniques and strategies for cortical dangerous veins during neurosurgical craniotomies.

Methods: We retrospectively analyzed 37 patients who underwent craniotomies involving the intraoperative protection of cortical dangerous veins between July 2022 and June 2024. Preoperatively, high-resolution magnetic resonance imaging data were used for three-dimensional visualization to delineate the resection margins and plan the management of related cortical dangerous veins, including bridging veins, superficial Sylvian veins, anastomotic veins, and veins in the eloquent cortex.

A peptide encoded by upstream open reading frame of binds to tropomyosin receptor kinase B and promotes glioblastoma growth in mice.

MYC promotes tumor growth through multiple mechanisms. Here, we show that, in human glioblastomas, the variant transcript encodes a 114-amino acid peptide, MYC pre-mRNA encoded protein (MPEP), from the upstream open reading frame (uORF) . Secreted MPEP promotes patient-derived xenograft tumor growth in vivo, independent of MYC through direct binding, and activation of tropomyosin receptor kinase B (TRKB), which induces downstream AKT-mTOR signaling.

SAD score of intracranial aneurysms for rupture risk assessment based on high-resolution vessel wall imaging.

Objective: We aimed to develop a comprehensive model that integrates the radiological, morphological, and clinical factors to assess rupture risk for intracranial aneurysms.

Methods: We prospectively enrolled patients with intracranial saccular aneurysms who underwent high-resolution vessel wall imaging (HR-VWI) preoperatively. Clinical characteristics, aneurysm features and aneurysm wall enhancement scale (AWES) were recorded.

Risk Factors for Cerebral Infarction After Microsurgical Clipping of Hunt-Hess Grade 0-2 Single Intracranial Aneurysm: A Retrospective Study.

Objective: The study aimed to explore risk factors for cerebral infarction after microsurgical clipping in patients with Hunt-Hess grade 0-2 single intracranial aneurysms.

Methods: A total of 137 patients with Hunt-Hess grade 0-2 single intracranial aneurysms treated with microsurgical clipping between March 2017 and December 2020 were retrospectively enrolled. Patients were divided into 2 groups on the basis of the occurrence of cerebral infarction after surgery.

Circ-E-Cad encodes a protein that promotes the proliferation and migration of gastric cancer via the TGF-β/Smad/C-E-Cad/PI3K/AKT pathway.

Accumulating studies indicate that circular RNAs (circRNAs) play critical roles in cancer progression. Most of them have been reported to act as microRNA sponges or interact with RNA-binding proteins; however, their full range of functions remains largely unclear. Recently, an increasing number of circRNAs have been found to encode proteins.

A novel protein RASON encoded by a lncRNA controls oncogenic RAS signaling in KRAS mutant cancers.

Mutations of the RAS oncogene are found in around 30% of all human cancers yet direct targeting of RAS is still considered clinically impractical except for the KRAS mutant. Here we report that RAS-ON (RASON), a novel protein encoded by the long intergenic non-protein coding RNA 00673 (LINC00673), is a positive regulator of oncogenic RAS signaling. RASON is aberrantly overexpressed in pancreatic ductal adenocarcinoma (PDAC) patients, and it promotes proliferation of human PDAC cell lines in vitro and tumor growth in vivo.

TRPV1 sensory nerves modulate corneal inflammation after epithelial abrasion via RAMP1 and SSTR5 signaling.

Timely initiation and termination of inflammatory response after corneal epithelial abrasion is critical for the recovery of vision. The cornea is innervated with rich sensory nerves with highly dense TRPV1 nociceptors. However, the roles of TRPV1 sensory neurons in corneal inflammation after epithelial abrasion are not completely understood.

Autonomic nervous system receptor-mediated regulation of mast cell degranulation modulates the inflammation after corneal epithelial abrasion.

Mast cells (MCs) regulate wound healing and are influenced by the autonomic nervous system (ANS). However, the underlying mechanisms affecting wound healing outcomes remain elusive. Here, we explored the specific role of the ANS by regulating MC degranulation following corneal epithelium abrasion.

Circular RNA-encoded oncogenic E-cadherin variant promotes glioblastoma tumorigenicity through activation of EGFR-STAT3 signalling.

Activated EGFR signalling drives tumorigenicity in 50% of glioblastoma (GBM). However, EGFR-targeting therapy has proven ineffective in treating patients with GBM, indicating that there is redundant EGFR activation. Circular RNAs are covalently closed RNA transcripts that are involved in various physiological and pathological processes.

A novel protein encoded by circular SMO RNA is essential for Hedgehog signaling activation and glioblastoma tumorigenicity.

Background: Aberrant activation of the Hedgehog pathway drives tumorigenesis of many cancers, including glioblastoma. However, the sensitization mechanism of the G protein-coupled-like receptor smoothened (SMO), a key component of Hedgehog signaling, remains largely unknown.

Results: In this study, we describe a novel protein SMO-193a.

An Upstream Open Reading Frame in Phosphatase and Tensin Homolog Encodes a Circuit Breaker of Lactate Metabolism.

The metabolic role of micropeptides generated from untranslated regions remains unclear. Here we describe MP31, a micropeptide encoded by the upstream open reading frame (uORF) of phosphatase and tensin homolog (PTEN) acting as a "circuit breaker" that limits lactate-pyruvate conversion in mitochondria by competing with mitochondrial lactate dehydrogenase (mLDH) for nicotinamide adenine dinucleotide (NAD). Knocking out the MP31 homolog in mice enhanced global lactate metabolism, manifesting as accelerated oxidative phosphorylation (OXPHOS) and increased lactate consumption and production.

Sympathetic Nerves Positively Regulate Eosinophil-Driven Allergic Conjunctivitis via α1-Adrenergic Receptor Signaling.

Eosinophils are a major cause of tissue injury in allergic conjunctivitis. The biological nature of eosinophils in the conjunctiva and the mechanisms that control eosinophils' responses in allergic conjunctivitis are currently not completely understood. This study reports that conjunctival eosinophils comprise two populations-Siglec-F and Siglec-F-in different life stages.

Correction to: A novel tumor suppressor protein encoded by circular AKT3 RNA inhibits glioblastoma tumorigenicity by competing with active phosphoinositide-dependent Kinase-1.

In the published article [1], an error was noticed in Fig. 6B. The western blot results were reversed between the overexpression group and the knockdown group of circ-AKT3.

A novel tumor suppressor protein encoded by circular AKT3 RNA inhibits glioblastoma tumorigenicity by competing with active phosphoinositide-dependent Kinase-1.

Background: The RTK/PI3K/AKT pathway plays key roles in the development and progression of many cancers, including GBM. As a regulatory molecule and a potential drug target, the oncogenic role of AKT has been substantially studied. Three isoforms of AKT have been identified, including AKT1, AKT2 and AKT3, but their individual functions in GBM remain controversial.

Antibiotic-induced dysbiosis of gut microbiota impairs corneal development in postnatal mice by affecting CCR2 negative macrophage distribution.

Antibiotics are extremely useful, but they can cause adverse impacts on host bodies. We found that antibiotic treatment altered the composition of the gut microbiota and the gene expression profile in the corneal tissues of postnatal mice and decreased the corneal size and thickness, the angiogenesis of limbal blood vessels, and the neurogenesis of corneal nerve fibers. The reconstitution of the gut microbiota with fecal transplants in antibiotic-treated mice largely reversed these impairments in corneal development.

Donor platelet plasma components inactivate sensitive and multidrug resistant Acinetobacter baumannii isolates.

Acinetobacter baumannii is an environmentally resilient healthcare-associated opportunistic pathogen responsible for infections at many body sites. In the last 10 years, clinical strains resistant to many or all commonly used antibiotics have emerged globally. With few antimicrobial agents in the pharmaceutical pipeline, new and alternative agents are essential.

Gene electro transfer of plasmid encoding vascular endothelial growth factor for enhanced expression and perfusion in the ischemic swine heart.

Myocardial ischemia can damage heart muscle and reduce the heart's pumping efficiency. This study used an ischemic swine heart model to investigate the potential for gene electro transfer of a plasmid encoding vascular endothelial growth factor for improving perfusion and, thus, for reducing cardiomyopathy following acute coronary syndrome. Plasmid expression was significantly greater in gene electro transfer treated tissue compared to injection of plasmid encoding vascular endothelial growth factor alone.

Controlled gene delivery can enhance therapeutic outcome for cancer immune therapy for melanoma.

Effective delivery still remains a major hurdle in the development of gene based therapies. While technological advances have occurred that have improved delivery in general, there is still a need for controlled delivery in order to achieve therapeutic effects. Gene electrotransfer (GET) can be utilized to accomplish this.

Excretion and metabolism of milnacipran in humans after oral administration of milnacipran hydrochloride.

The pharmacokinetics, excretion, and metabolism of milnacipran were evaluated after oral administration of a 100-mg dose of [¹⁴C]milnacipran hydrochloride to healthy male subjects. The peak plasma concentration of unchanged milnacipran (∼240 ng/ml) was attained at 3.5 h and was lower than the peak plasma concentration of radioactivity (∼679 ng Eq of milnacipran/ml) observed at 4.

Mass balance and metabolism of aclidinium bromide following intravenous administration of [¹⁴C]-aclidinium bromide in healthy subjects.

Aclidinium bromide is a novel, inhaled long-acting muscarinic antagonist with low systemic activity developed for the treatment of COPD. It is an ester compound rapidly hydrolysed in plasma into inactive alcohol and acid metabolites. In this Phase I, open-label study, the rates and routes of elimination of radioactivity following intravenous administration of [¹⁴C]-aclidinium bromide were determined.