Determination of doping higenamine in Chinese herbal medicines and their concentrated preparations by LC-MS/MS.

The World Anti-Doping Agency (WADA) has included higenamine in the β2 agonist (S3) category of the Prohibited List since 2017 due to its pharmacological effects on adrenergic receptors. Although higenamine contained in Chinese herbal medicines has been identified by previous studies, comprehensive investigation on the higenamine content of Chinese herbs and their concentrated preparations is still required. This study aimed to determine the levels of higenamine in Chinese medicinal materials and their concentrated preparations used in Chinese medicine prescriptions in Taiwan.

Targeting PRMT1-mediated SRSF1 methylation to suppress oncogenic exon inclusion events and breast tumorigenesis.

PRMT1 plays a vital role in breast tumorigenesis; however, the underlying molecular mechanisms remain incompletely understood. Herein, we show that PRMT1 plays a critical role in RNA alternative splicing, with a preference for exon inclusion. PRMT1 methylome profiling identifies that PRMT1 methylates the splicing factor SRSF1, which is critical for SRSF1 phosphorylation, SRSF1 binding with RNA, and exon inclusion.

Antrodia salmonea suppresses epithelial-mesenchymal transition/metastasis and Warburg effects by inhibiting Twist and HIF-1α expression in Twist-overexpressing head and neck squamous cell carcinoma cells.

Ethnopharmacological Relevance: Antrodia salmonea (AS), linked to the genus Taiwanofungus, is a medicinal fungus, and exhibits anti-inflammatory, anti-oxidant, and tumor inhibiting properties.

Aim Of The Study: In this study, we investigated the metabolic reprogramming and anti-metastasis/epithelial-mesenchymal transition (EMT) effects of AS exposure in Twist-overexpressing head and neck squamous cell carcinoma (HNSCC, OECM-1 and FaDu-Twist) cells.

Materials And Methods: MTT assay, Western blot, migration/invasion assay, immunofluorescence, glucose uptake assay, lactate assay, oxygen consumption rate (OCR)/Extracellular acidification rate (ECAR) assay, Liquid Chromatography-Electrospray Ionization Tandem Mass Spectrometry (LC-ESI-MS), and qRT-PCR experimental techniques were used to evaluate the therapeutic potential of AS treatment in HNSCC cells.

In vitro and in vivo anti-tumor activity of Coenzyme Q against TWIST1-overexpressing HNSCC cells: ROS-mediated inhibition of EMT/metastasis and autophagy/apoptosis induction.

HNSCC (Head and Heck Squamous Cell Carcinoma) is a reasonably prevalent cancer with a high mortality rate. In this study, we tried to examine the anti-metastasis and apoptosis/autophagy actions of Coenzyme Q (CoQ, 2,3-dimethoxy-5-methyl-1,4-benzoquinone), a derivative of Antrodia camphorata in HNCC TWIST1 overexpressing (FaDu-TWIST1) cells as well as in vivo tumor xenograft mice model. Using fluorescence based cellular assays, western blot and nude mice tumor xenografts, we determined that CoQ effectively reduced cell viability and displayed rapid morphological changes in FaDu-TWIST1 cells compared to FaDu cells.

Coenzyme Q defeats NLRP3-mediated inflammation, EMT/metastasis, and Warburg effects by inhibiting HIF-1α expression in human triple-negative breast cancer cells.

Coenzyme Q (CoQ) is a derivative quinone from Antrodia camphorata (AC) that exerts anticancer activities. This study examined the anticancer attributes of CoQ (0-4 µM) on inhibited anti-EMT/metastasis and NLRP3 inflammasome, and altered Warburg effects via HIF-1α inhibition in triple-negative breast cancer (MDA-MB-231 and 468) cells. MTT assay, cell migration/invasion assays, Western blotting, immunofluorescence, metabolic reprogramming, and LC-ESI-MS were carried out to assess the therapy potential of CoQ.

In vitro and in vivo anti-tumor activity of Antrodia salmonea against twist-overexpressing HNSCC cells: Induction of ROS-mediated autophagic and apoptotic cell death.

Head and neck squamous cell carcinoma (HNSCC) is a relatively common malignancy, characterized by lethal morbidity. Herein, we attempted to investigate the autophagy/apoptosis activities of the submerged fermented broths of Antrodia salmonea (AS) in HNSCC Twist-overexpressing (OECM-1 and FaDu-Twist) cells. AS (0-150 μg/mL) effectively reduced cell viability, colony formation, and downregulated Twist expression in OECM-1 and FaDu-Twist cells compared to FaDu cells.

Urinary excretion patterns and potential risks of beta-blocker ophthalmic drops in sports.

Beta-blockers have been prohibited by the World Anti-Doping Agency (WADA) in certain sports, but insufficient research data make it difficult to distinguish between therapeutic uses or misuses. This study aimed at investigating the urinary excretion pattern following beta-blocker ophthalmic drops and the potential risk of constituting an adverse analytical finding (AAF) in sports. Prescribed timolol and carteolol ophthalmic drops were used in healthy participants and glaucoma patients.

American Ginseng Attenuates Eccentric Exercise-Induced Muscle Damage via the Modulation of Lipid Peroxidation and Inflammatory Adaptation in Males.

Exercise-induced muscle damage (EIMD) is characterized by a reduction in functional performance, disruption of muscle structure, production of reactive oxygen species, and inflammatory reactions. Ginseng, along with its major bioactive component ginsenosides, has been widely employed in traditional Chinese medicine. The protective potential of American ginseng (AG) for eccentric EIMD remains unclear.

Lactiplantibacillus plantarum PS128 Alleviates Exaggerated Cortical Beta Oscillations and Motor Deficits in the 6-Hydroxydopamine Rat Model of Parkinson's Disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by midbrain dopaminergic neuronal loss and subsequent physical impairments. Levodopa manages symptoms best, while deep brain stimulation (DBS) is effective for advanced PD patients; however, side effects occur with the diminishing therapeutic window. Recently, Lactiplantibacillus plantarum PS128 (PS128) was found to elevate dopamine levels in rodent brains, suggesting its potential to prevent PD.

Activation of IGF-1 pathway and suppression of atrophy related genes are involved in Epimedium extract (icariin) promoted C2C12 myotube hypertrophy.

The regenerative effect of Epimedium and its major bioactive flavonoid icariin (ICA) have been documented in traditional medicine, but their effect on sarcopenia has not been evaluated. The aim of this study was to investigate the effects of Epimedium extract (EE) on skeletal muscle as represented by differentiated C2C12 cells. Here we demonstrated that EE and ICA stimulated C2C12 myotube hypertrophy by activating several, including IGF-1 signal pathways.

Profiling PRMT methylome reveals roles of hnRNPA1 arginine methylation in RNA splicing and cell growth.

Numerous substrates have been identified for Type I and II arginine methyltransferases (PRMTs). However, the full substrate spectrum of the only type III PRMT, PRMT7, and its connection to type I and II PRMT substrates remains unknown. Here, we use mass spectrometry to reveal features of PRMT7-regulated methylation.

Systemic dendrimer-drug nanomedicines for long-term treatment of mild-moderate cerebral palsy in a rabbit model.

Background: Neuroinflammation mediated by microglia plays a central role in the pathogenesis of perinatal/neonatal brain injury, including cerebral palsy (CP). Therapeutics mitigating neuroinflammation potentially provide an effective strategy to slow the disease progression and rescue normal brain development. Building on our prior results which showed that a generation-4 hydroxyl poly(amidoamine) (PAMAM) dendrimer could deliver drugs specifically to activated glia from systemic circulation, we evaluated the sustained efficacy of a generation-6 (G6) hydroxyl-terminated PAMAM dendrimer that showed a longer blood circulation time and increased brain accumulation.

Antiproliferative and Antimetastatic Effects of Praeruptorin C on Human Non-Small Cell Lung Cancer Through Inactivating ERK/CTSD Signalling Pathways.

Praeruptorin C (PC) reportedly has beneficial effects in terms of antiinflammation, antihypertension, and antiplatelet aggregation, and it potentially has anticancer activity. However, the effect of PC on human non-small cell lung cancer (NSCLC) is largely unknown. Compared with the effects of praeruptorin A and praeruptorin B, we observed that PC significantly suppressed cell proliferation, colony formation, wound closure, and migration and invasion of NSCLC cells.

Synthesis of Mikto-Arm Star Peptide Conjugates.

Mikto-arm star peptide conjugates are an emerging class of self-assembling peptide-based structural units that contain three or more auxiliary segments of different chemical compositions and/or functionalities. This group of molecules exhibit interesting self-assembly behavior in solution due to their chemically asymmetric topology. Here we describe the detailed procedure for synthesis of an ABC Mikto-arm star peptide conjugate in which two immiscible entities (a saturated hydrocarbon and a hydrophobic and lipophobic fluorocarbon) are conjugated onto a short β-sheet forming peptide sequence, GNNQQNY, derived from the Sup35 prion, through a lysine junction.

Isomeric control of the mechanical properties of supramolecular filament hydrogels.

Supramolecular filament hydrogels are an emerging class of biomaterials that hold great promise for regenerative medicine, tissue engineering, and drug delivery. However, fine-tuning of their bulk mechanical properties at the molecular level without altering their network structures remains a significant challenge. Here we report an isomeric strategy to construct amphiphilic peptides through the conjugation of isomeric hydrocarbons to influence the local viscoelastic properties of their resulting supramolecular hydrogels.

Bifunctional Elastin-like Polypeptide Nanoparticles Bind Rapamycin and Integrins and Suppress Tumor Growth in Vivo.

Recombinant protein-polymer scaffolds such as elastin-like polypeptides (ELPs) offer drug-delivery opportunities including biocompatibility, monodispersity, and multifunctionality. We recently reported that the fusion of FK-506 binding protein 12 (FKBP) to an ELP nanoparticle (FSI) increases rapamycin (Rapa) solubility, suppresses tumor growth in breast cancer xenografts, and reduces side effects observed with free-drug controls. This new report significantly advances this carrier strategy by demonstrating the coassembly of two different ELP diblock copolymers containing drug-loading and tumor-targeting domains.

Enhancing clinical effectiveness of pre-radiotherapy workflow by using multidisciplinary-cooperating e-control and e-alerts: A SQUIRE-compliant quality-improving study.

Radiotherapy (RT) is useful in managing cancer diseases. In clinical practice, early initiation of RT is crucial for enhancing tumor control. But, delivering precise RT requires a series of pre-RT working processes in a tight staff-cooperation manner.

Selective Localization of a Novel Dendrimer Nanoparticle in Myocardial Ischemia-Reperfusion Injury.

Background: Dendrimer nanoparticle therapies represent promising new approaches to drug delivery, particularly in diseases associated with inflammatory injury. However, their application has not been fully explored in models of acute myocardial ischemia (MI) and reperfusion injury.

Methods: White male New Zealand rabbits underwent left thoracotomy with 30-minute temporary left anterior descending artery occlusion and MI confirmed by electrocardiography and histology (MI rabbits, n = 9), or left thoracotomy and pericardial opening for 30 minutes but no left anterior descending artery occlusion (control [C] rabbits, n = 9) rabbits.

Molecular design and synthesis of self-assembling camptothecin drug amphiphiles.

The conjugation of small molecular hydrophobic anticancer drugs onto a short peptide with overall hydrophilicity to create self-assembling drug amphiphiles offers a new prodrug strategy, producing well-defined, discrete nanostructures with a high and quantitative drug loading. Here we show the detailed synthesis procedure and how the molecular structure can influence the synthesis of the self-assembling prodrugs and the physicochemical properties of their assemblies. A series of camptothecin-based drug amphiphiles were synthesized via combined solid- and solution-phase synthetic techniques, and the physicochemical properties of their self-assembled nanostructures were probed using a number of imaging and spectroscopic techniques.

Use of polarization freedom beyond polarization-division multiplexing to support high-speed and spectral-efficient data transmission.

Increasing the system capacity and spectral efficiency (SE) per unit bandwidth is one of the ultimate goals for data network designers, especially when using technologies compatible with current embedded fiber infrastructures. Among these, the polarization-division-multiplexing (PDM) scheme, which supports two independent data channels on a single wavelength with orthogonal polarization states, has become a standard one in most state-of-art telecommunication systems. Currently, however, only two polarization states (that is, PDM) can be used, setting a barrier for further SE improvement.

Generation-6 hydroxyl PAMAM dendrimers improve CNS penetration from intravenous administration in a large animal brain injury model.

Hypothermic circulatory arrest (HCA) provides neuroprotection during cardiac surgery but entails an ischemic period that can lead to excitotoxicity, neuroinflammation, and subsequent neurologic injury. Hydroxyl polyamidoamine (PAMAM) dendrimers target activated microglia and damaged neurons in the injured brain, and deliver therapeutics in small and large animal models. We investigated the effect of dendrimer size on brain uptake and explored the pharmacokinetics in a clinically-relevant canine model of HCA-induced brain injury.

Implementing web-based ping-pong-type e-communication to enhance staff satisfaction, multidisciplinary cooperation, and clinical effectiveness: A SQUIRE-compliant quality-improving study.

Background: Frequent multidisciplinary communication is essential in conducting daily radiotherapy (RT) practice. However, traditional oral or paper-based communication has limitations. E-communication has been suggested, but its effects are still not well demarcated in the field of radiation oncology.

Extremely Low Frequency Electromagnetic Fields Facilitate Vesicle Endocytosis by Increasing Presynaptic Calcium Channel Expression at a Central Synapse.

Accumulating evidence suggests significant biological effects caused by extremely low frequency electromagnetic fields (ELF-EMF). Although exo-endocytosis plays crucial physical and biological roles in neuronal communication, studies on how ELF-EMF regulates this process are scarce. By directly measuring calcium currents and membrane capacitance at a large mammalian central nervous synapse, the calyx of Held, we report for the first time that ELF-EMF critically affects synaptic transmission and plasticity.

Targeting specific cells in the brain with nanomedicines for CNS therapies.

Treatment of Central Nervous System (CNS) disorders still remains a major clinical challenge. The Blood-Brain Barrier (BBB), known as the major hindrance, greatly limits therapeutics penetration into the brain. Moreover, even though some therapeutics can cross BBB based on their intrinsic properties or via the use of proper nanoscale delivery vehicles, their therapeutic efficacy is still often limited without the specific uptake of drugs by the cancer or disease-associated cells.