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Scientific Reports Jun 2024The present study aimed to assess the effectiveness and functional adverse effects of a single and multiple injections of botulinum toxin A (BoNT-A) for masseter... (Randomized Controlled Trial)
Randomized Controlled Trial
The present study aimed to assess the effectiveness and functional adverse effects of a single and multiple injections of botulinum toxin A (BoNT-A) for masseter hypertrophy (MH). Twenty-six women complaining about lower third facial enlargement due to MH, received 75 U of BoNT-A (abobotulinum toxin) in each masseter muscles. After 3 months, patients were randomly assigned to receive a second treatment session of Saline Solution: (G1; n = 11) or BoNT-A: (G2; n = 12). Muscle thickness (ultrasound), electrical activity (electromyography; EMG), masticatory performance, and subjective perception of MH were evaluated. Follow-up was performed at 1, 3 and 6 months. Muscle thickness, EMG activity, and masticatory performance were analyzed using ANOVA two-way and Sidak test as post-hoc. Masticatory performance was analyzed by the Friedman's test and Mann-Whitney test. Regarding inter-groups comparisons, there was a significant decrease in the left masseter muscle thickness in the G2 group at the 6 month follow-up (p < 0.02). For EMG, significant differences were evident at the 6 month assessment, with higher masseter activity for G1 (p < 0.05). For masticatory performance, no significant differences were observed throughout the study (p > 0.05) and a higher improvement in subjective perception of MH was observed in the 1 month follow-up for G2 (p < 0.05). In conclusion, BoNT-A is effective for MH, however multiple injections cause functional adverse effects in masseter muscle.
Topics: Humans; Masseter Muscle; Female; Hypertrophy; Botulinum Toxins, Type A; Adult; Electromyography; Mastication; Middle Aged; Treatment Outcome; Neuromuscular Agents; Injections, Intramuscular
PubMed: 38914688
DOI: 10.1038/s41598-024-65395-5 -
Sheng Wu Gong Cheng Xue Bao = Chinese... Jun 2024Plant synthetic biology has significant theoretical advantages in exploration and production of plant natural products. However, its contribution to the field of...
Plant synthetic biology has significant theoretical advantages in exploration and production of plant natural products. However, its contribution to the field of biosynthesis is currently limited due to the lack of efficient chassis systems and related enabling technologies. Synthetic biologists often avoid tobacco as a chassis system because of its long operation cycle, difficulties in genetic and metabolic modification, complex metabolism and purification background, nicotine toxicity, and challenges in accurately controlling for agricultural production. Nevertheless, the tobacco suspension cell chassis system offers a viable solution to these challenges. The objective of this research was to develop a tobacco suspension cell chassis with high scientific and industrial potential. This chassis should exhibit rapid growth, high biomass, excellent dispersion, high transformation efficiency, and minimal nicotine content. , which has high applicability in molecular technology, was used to induce suspension cells. The induced suspension cells, named NBS-1, exhibited rapid growth, excellent dispersion, and high biomass, reaching a maximum biomass of 476.39 g/L (fresh weight), which was significantly higher than that of BY-2. The transformation efficiency of the widely utilized pEAQ-HT transient expression system in NBS-1 reached 81%, which was substantially elevated compared to BY-2. The metabolic characteristics and bias of BY-2 and NBS-1 were analyzed using transcriptome data. It was found that the gene expression of pathways related to biosynthesis of flavonoids and their derivatives in NBS-1 was significantly higher, while the pathways related to alkaloid biosynthesis were significantly lower compared to BY-2. These findings were further validated by the total content of flavonoid and alkaloid. In summary, our research demonstrates NBS-1 possesses minimal nicotine content and provides valuable guidance for selecting appropriate chassis for specific products. In conclusion, this study developed NBS-1, a tobacco suspension cell chassis with excellent growth and transformation, high flavonoid content and minimal nicotine content, which has important guiding significance for the development of tobacco suspension cell chassis.
Topics: Nicotiana; Synthetic Biology; Plants, Genetically Modified; Metabolic Engineering; Cell Culture Techniques; Nicotine; Biomass
PubMed: 38914502
DOI: 10.13345/j.cjb.230735 -
Frontiers in Immunology 2024Myasthenia gravis with positive MuSK antibody often involves the bulbar muscles and is usually refractory to acetylcholinesterase inhibitors. For MuSK-MG patients who...
Myasthenia gravis with positive MuSK antibody often involves the bulbar muscles and is usually refractory to acetylcholinesterase inhibitors. For MuSK-MG patients who experience acute exacerbations and do not respond to conventional treatments, there is an urgent need to find more suitable treatment options. With the advent of biologic agents, efgartigimod has shown promising results in the treatment of MG. We report a 65-year-old MuSK-MG patient who presented with impaired eye movements initially, and the symptoms rapidly worsened within a week, affecting the limbs and neck muscles, and had difficulties in chewing and swallowing. Lymphoplasmapheresis did not achieve satisfactory results, but after a cycle of efgartigimod treatment, the patient's symptoms gradually improved and remained in a good clinical state for several months.
Topics: Humans; Myasthenia Gravis; Aged; Receptors, Cholinergic; Treatment Outcome; Receptor Protein-Tyrosine Kinases; Autoantibodies; Male; Female
PubMed: 38911858
DOI: 10.3389/fimmu.2024.1401972 -
Future Medicinal Chemistry 2024To design and synthesize a novel series of 1-aryldonepezil analogues. The 1-aryldonepezil analogues were synthesized through palladium/PCy-catalyzed Suzuki reaction...
To design and synthesize a novel series of 1-aryldonepezil analogues. The 1-aryldonepezil analogues were synthesized through palladium/PCy-catalyzed Suzuki reaction and were evaluated for cholinesterase inhibitory activities and neuroprotective effects. docking of the most effective compound was conducted. The 4--butylphenyl analogue exhibited good inhibitory potency against acetylcholinesterase and butyrylcholinesterase and had a favorable neuroprotective effect on HO-induced SH-SY5Y cell injury. The 4--butylphenyl derivative is a promising lead compound for anti-Alzheimer's disease drug development.
Topics: Alzheimer Disease; Humans; Cholinesterase Inhibitors; Drug Design; Neuroprotective Agents; Acetylcholinesterase; Butyrylcholinesterase; Molecular Docking Simulation; Structure-Activity Relationship; Piperidines; Molecular Structure; Cell Line, Tumor; Hydrogen Peroxide; Indoles
PubMed: 38910574
DOI: 10.4155/fmc-2023-0369 -
Scientific Reports Jun 2024Head-fixation of mice enables high-resolution monitoring of neuronal activity coupled with precise control of environmental stimuli. Virtual reality can be used to...
Head-fixation of mice enables high-resolution monitoring of neuronal activity coupled with precise control of environmental stimuli. Virtual reality can be used to emulate the visual experience of movement during head fixation, but a low inertia floating real-world environment (mobile homecage, MHC) has the potential to engage more sensory modalities and provide a richer experimental environment for complex behavioral tasks. However, it is not known whether mice react to this adapted environment in a similar manner to real environments, or whether the MHC can be used to implement validated, maze-based behavioral tasks. Here, we show that hippocampal place cell representations are intact in the MHC and that the system allows relatively long (20 min) whole-cell patch clamp recordings from dorsal CA1 pyramidal neurons, revealing sub-threshold membrane potential dynamics. Furthermore, mice learn the location of a liquid reward within an adapted T-maze guided by 2-dimensional spatial navigation cues and relearn the location when spatial contingencies are reversed. Bilateral infusions of scopolamine show that this learning is hippocampus-dependent and requires intact cholinergic signalling. Therefore, we characterize the MHC system as an experimental tool to study sub-threshold membrane potential dynamics that underpin complex navigation behaviors.
Topics: Animals; Mice; Spatial Navigation; Maze Learning; Male; Hippocampus; Pyramidal Cells; Mice, Inbred C57BL; Membrane Potentials; CA1 Region, Hippocampal; Virtual Reality; Scopolamine; Patch-Clamp Techniques
PubMed: 38906952
DOI: 10.1038/s41598-024-64807-w -
JMIR Research Protocols Jun 2024Cigarette smoking is a leading cause of morbidity and mortality. For adults who smoke cigarettes and cannot or will not quit smoking, smoke-free products, such as... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Cigarette smoking is a leading cause of morbidity and mortality. For adults who smoke cigarettes and cannot or will not quit smoking, smoke-free products, such as nicotine pouches, have been recognized as a potential alternative to smoking combusted cigarettes to reduce harm due to cigarette smoking. The role of flavors in these smoke-free products in tobacco harm reduction has not been fully understood.
OBJECTIVE
This study evaluates the effect of flavors in on! nicotine pouch products (research products) in the reduction of cigarette smoking among adults who smoke cigarettes in their natural environment.
METHODS
This study uses a sequential, multiple assignment, randomized trial design. Approximately 400 eligible adults who smoke cigarettes will be enrolled and randomized to have access to either the Original (unflavored) on! nicotine pouch product only or a complete flavor profile (ie, Berry, Cinnamon, Citrus, Coffee, Mint, Original, and Wintergreen) of on! nicotine pouch products. After 3 weeks, participants in the Original-only arm will be randomized again, with half remaining in the Original-only arm and half having access to the complete flavor profile for another 3 weeks. Primary outcomes are expired-air carbon monoxide (CO) levels. Secondary outcomes are self-reported cigarette consumption and CO-verified cigarette abstinence.
RESULTS
Recruitment and data collection started in September 2023 and is projected to last until March 2025. We anticipate completing the data analysis in 2025. As of May 2024, we have enrolled 314 participants.
CONCLUSIONS
This study will provide empirical evidence about the effect that flavor availability in smoke-free products may have in reducing cigarette smoking.
TRIAL REGISTRATION
ClinicalTrials.gov NCT06072547; https://clinicaltrials.gov/study/NCT06072547.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/56565.
Topics: Humans; Flavoring Agents; Adult; Female; Male; Smoking Cessation; Nicotine; Middle Aged; Smoking; Tobacco Products
PubMed: 38905632
DOI: 10.2196/56565 -
Journal of Neural Transmission (Vienna,... Jun 2024Anticholinergic (AC) drugs, a medication class that acts by blocking nicotinic and muscarinic acetylcholine receptors, were first utilized for therapeutic purposes in... (Review)
Review
Anticholinergic (AC) drugs, a medication class that acts by blocking nicotinic and muscarinic acetylcholine receptors, were first utilized for therapeutic purposes in the mid-19th century. Initial applications were as symptomatic therapy for Parkinson disease (PD), a practice continuing to the present. Initially, the AC drugs used were naturally-occurring plant compounds. Synthetic AC drugs were developed in the late 1940s and predominated in neurological therapeutics. Until the advent of pharmaceuticals acting upon striatal dopaminergic motor pathways, AC drugs provided the only effective means for lessening tremors and other clinical problems of the PD patient. However, because dopaminergic compounds are so effective at meeting the needs of the typical PD patient, AC medications are far less utilized by clinicians today. In recent years, there has been only a few investigations of AC drugs as neurological treatments. This review will revisit the clinical landscape of AC pharmacology and application for movement disorders along with recent research in search of improving therapeutics with AC drugs.
PubMed: 38904792
DOI: 10.1007/s00702-024-02799-7 -
Current Findings and Potential Mechanisms of KarXT (Xanomeline-Trospium) in Schizophrenia Treatment.Clinical Drug Investigation Jun 2024Standard schizophrenia treatment involves antipsychotic medications that target D2 dopamine receptors. However, these drugs have limitations in addressing all symptoms... (Review)
Review
Standard schizophrenia treatment involves antipsychotic medications that target D2 dopamine receptors. However, these drugs have limitations in addressing all symptoms and can lead to adverse effects such as motor impairments, metabolic effects, sedation, sexual dysfunction, cognitive impairment, and tardive dyskinesia. Recently, KarXT has emerged as a novel drug for schizophrenia. KarXT combines xanomeline, a muscarinic receptor M1 and M4 agonist, with trospium, a nonselective antimuscarinic agent. Of note, xanomeline can readily cross blood-brain barrier (BBB) and, thus, enter into the brain, thereby stimulating muscarinic receptors (M1 and M4). By doing so, xanomeline has been shown to target negative symptoms and potentially improve positive symptoms. Trospium, on the other hand, is not able to cross BBB, thereby not affecting M1 and M4 receptors; instead, it acts as an antimuscarinic agent and, hence, diminishes peripheral activity of muscarinic receptors to minimize side effects probably stemming from xanomeline in other organs. Accordingly, ongoing clinical trials investigating KarXT's efficacy in schizophrenia have demonstrated positive outcomes, including significant improvements in the Positive and Negative Syndrome Scale (PANSS) total score and cognitive function compared with placebo. These findings emphasize the potential of KarXT as a promising treatment for schizophrenia, providing symptom relief while minimizing side effects associated with xanomeline monotherapy. Despite such promising evidence, further research is needed to confirm the efficacy, safety, and tolerability of KarXT in managing schizophrenia. This review article explores the current findings and potential mechanisms of KarXT in the treatment of schizophrenia.
PubMed: 38904739
DOI: 10.1007/s40261-024-01377-9 -
Archives of Microbiology Jun 2024Cotinine, the primary metabolite of nicotine in the human body, is an emerging pollutant in aquatic environments. It causes environmental problems and is harmful to the...
Cotinine, the primary metabolite of nicotine in the human body, is an emerging pollutant in aquatic environments. It causes environmental problems and is harmful to the health of humans and other mammals; however, the mechanisms of its biodegradation have been elucidated incompletely. In this study, a novel Gram-negative strain that could degrade and utilize cotinine as a sole carbon source was isolated from municipal wastewater samples, and its cotinine degradation characteristics and kinetics were determined. Pseudomonas sp. JH-2 was able to degrade 100 mg/L (0.56 mM) of cotinine with high efficiency within 5 days at 30 ℃, pH 7.0, and 1% NaCl. Two intermediates, 6-hydroxycotinine and 6-hydroxy-3-succinoylpyridine (HSP), were identified by high-performance liquid chromatography and liquid chromatograph mass spectrometer. The draft whole genome sequence of strain JH-2 was obtained and analyzed to determine genomic structure and function. No homologs of proteins predicted in Nocardioides sp. JQ2195 and reported in nicotine degradation Pyrrolidine pathway were found in strain JH-2, suggesting new enzymes that responsible for cotinine catabolism. These findings provide meaningful insights into the biodegradation of cotinine by Gram-negative bacteria.
Topics: Pseudomonas; Biodegradation, Environmental; Cotinine; Wastewater; Nicotine; Pyridines; Genome, Bacterial; Phylogeny; Succinates
PubMed: 38904699
DOI: 10.1007/s00203-024-04036-x -
Scientific Reports Jun 2024Acetylcholine (ACh) plays a pivotal role as a neurotransmitter, influencing nerve cell communication and overall nervous system health. Imbalances in ACh levels are...
Acetylcholine (ACh) plays a pivotal role as a neurotransmitter, influencing nerve cell communication and overall nervous system health. Imbalances in ACh levels are linked to neurodegenerative diseases, such as Alzheimer's and Parkinson's. This study focused on developing electrochemical sensors for ACh detection, utilizing graphene oxide (GO) and a composite of reduced graphene oxide and zinc oxide (rGO/ZnO). The synthesis involved modified Hummers' and hydrothermal methods, unveiling the formation of rGO through deoxygenation and the integration of nano-sized ZnO particles onto rGO, as demonstrated by XPS and TEM. EIS analysis also revealed the enhancement of electron transfer efficiency in rGO/ZnO. Cyclic voltammograms of the electrode, comprising the rGO/ZnO composite in ACh solutions, demonstrated prominent oxidation and reduction reactions. Notably, the composite exhibited promise for ACh detection due to its sensitivity, low detection threshold, reusability, and selectivity against interfering compounds, specifically glutamate and gamma-aminobutyric acid. The unique properties of rGO, such as high specific surface area and electron mobility, coupled with ZnO's stability and catalytic efficiency, contributed to the composite's potential in electrochemical sensor applications. This research, emphasizing the synthesis, fabrication, and characterization of the rGO/ZnO composite, established itself as a reliable platform for detecting the acetylcholine neurotransmitter.
Topics: Graphite; Zinc Oxide; Acetylcholine; Electrochemical Techniques; Oxidation-Reduction; Electrodes; Biosensing Techniques; Humans
PubMed: 38902301
DOI: 10.1038/s41598-024-64238-7