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Reumatismo Jun 2024Nicotine has major side effects on human health through numerous mechanisms, one of which is the alteration of the immune system and its genetic components. Such... (Review)
Review
OBJECTIVE
Nicotine has major side effects on human health through numerous mechanisms, one of which is the alteration of the immune system and its genetic components. Such alteration can be a predisposing factor for autoimmune diseases such as spondyloarthritis (SpA) and rheumatoid arthritis (RA). This review aims to shed light on the effects of nicotine smoking on the pathophysiology, clinical presentation, and management of SpA and RA.
METHODS
This review looked into the studies, excluding case reports and series, which were cited by PubMed/MEDLINE.
RESULTS
Patients with established autoimmune conditions may have a different underlying pathophysiology and disease course when exposed to nicotine through cigarette smoking. Through the involvement of several cytokines, endothelial dysfunction, and epigenetic mechanisms, the severity of SpA is more prominent in smokers. The global health status, pain, and fatigue are worse in SpA patients. The evidence on the effect of nicotine smoking on the treatment of SpA is still limited. Nicotine can contribute to RA via the disruption of cellular regulatory activity, inflammatory responses, morphological, physiological, biochemical, and enzymatic responses. As such, smokers with RA have higher disease activity and are more likely to be seropositive through the citrullination of peptides. In addition, these patients are at risk of achieving a suboptimal response to tumor necrosis factor inhibitors.
CONCLUSIONS
Cigarette smoking can substantially affect the pathophysiology and clinical presentation of patients with SpA and RA. The impact of nicotine on the management of these diseases still needs to be further studied.
Topics: Humans; Arthritis, Rheumatoid; Nicotine; Spondylarthritis; Smoking
PubMed: 38916171
DOI: 10.4081/reumatismo.2024.1572 -
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 -
Biosensors & Bioelectronics Oct 2024An electrochemical (EC) sensor based on metalloporphyrin metal-organic framework (MOF) for the detection of parathion-methyl (PM) has been developed. The prepared...
An electrochemical (EC) sensor based on metalloporphyrin metal-organic framework (MOF) for the detection of parathion-methyl (PM) has been developed. The prepared MOF-525(Fe) exhibits great signal enhancement toward the electrochemical detection of PM owing to its unique structural properties and electrochemical activities. Under optimal experimental conditions, the as-prepared MOF-525(Fe) based EC sensor exhibited excellent PM sensing performance with a wide linear detection range (0.1 μM-100 μM) and low limit of detection (LOD, 1.4 nM). Compared to its corresponding Fe metalloporphyrin (linker), MOF-525(Fe) exhibited a superior sensitivity (28.31 μA cm·μM), which is 3.7 times higher than the sensitivity of FeTCPP linker (7.56 μA cm·μM) towards PM. The improved performance is associated with the high specific surface area and the large pore channels of MOF-525(Fe) facilitating a better interaction between PM and the Fe metalloporphyrin active sites, especially in the lower concentration range. Moreover, a possible affinity of the PM molecules toward Zr clusters may also contribute to the selective enrichment of PM on MOF-525(Fe). This EC sensor further demonstrated high selectivity in the presence of interfering molecules. The recovery results further confirm accurate PM sensing in actual samples, which suggests promising applications for the rapid detection of environmental organophosphates by metalloporphyrin MOFs.
Topics: Metal-Organic Frameworks; Electrochemical Techniques; Biosensing Techniques; Metalloporphyrins; Limit of Detection; Zirconium; Methyl Parathion
PubMed: 38909444
DOI: 10.1016/j.bios.2024.116515 -
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 -
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 -
Clinics (Sao Paulo, Brazil) 2024To investigate how language deteriorates over the Alzheimer's Disease course. (Observational Study)
Observational Study
OBJECTIVE
To investigate how language deteriorates over the Alzheimer's Disease course.
METHODS
A cross-sectional, observational study was carried out. 35 patients diagnosed with dementia due to AD using the NINCDS-ARDRA criteria and undergoing treatment for AD with a therapeutic dose of acetylcholinesterase inhibitors were assessed by the Boston Diagnostic Aphasia Examination (BDAE). The sample comprised 15 patients with mild AD (MMSE > 23, CDR = 0 or 0.5‒1.0) and 20 patients with moderate AD (MMSE = 13‒23, CDR = 2). The results for the 2 groups on all language tasks were compared.
RESULTS
A statistically significant difference was found between the mild and moderate AD groups for total score on the BDAE (95% CI 47.10‒114.08, t = 5.0, DF = 21, p = 0.000*), as well as on several tasks involving oral and writing comprehension, language oral expression and writing.
CONCLUSION
The study results showed major changes in the moderate stage. Also, the decline in language performance correlated with the worsening of dementia syndrome, independently of sociodemographic variables.
Topics: Humans; Alzheimer Disease; Male; Female; Cross-Sectional Studies; Aged; Severity of Illness Index; Aged, 80 and over; Language Disorders; Language Tests; Disease Progression; Neuropsychological Tests; Middle Aged; Socioeconomic Factors; Cholinesterase Inhibitors
PubMed: 38901132
DOI: 10.1016/j.clinsp.2024.100412 -
International Journal of Oral Science Jun 2024Oral submucous fibrosis (OSF) is a chronic and inflammatory mucosal disease caused by betel quid chewing, which belongs to oral potentially malignant disorders. Abnormal...
Oral submucous fibrosis (OSF) is a chronic and inflammatory mucosal disease caused by betel quid chewing, which belongs to oral potentially malignant disorders. Abnormal fibroblast differentiation leading to disordered collagen metabolism is the core process underlying OSF development. The epithelium, which is the first line of defense against the external environment, can convert external signals into pathological signals and participate in the remodeling of the fibrotic microenvironment. However, the specific mechanisms by which the epithelium drives fibroblast differentiation remain unclear. In this study, we found that Arecoline-exposed epithelium communicated with the fibrotic microenvironment by secreting exosomes. MiR-17-5p was encapsulated in epithelial cell-derived exosomes and absorbed by fibroblasts, where it promoted cell secretion, contraction, migration and fibrogenic marker (α-SMA and collagen type I) expression. The underlying molecular mechanism involved miR-17-5p targeting Smad7 and suppressing the degradation of TGF-β receptor 1 (TGFBR1) through the E3 ubiquitination ligase WWP1, thus facilitating downstream TGF-β pathway signaling. Treatment of fibroblasts with an inhibitor of miR-17-5p reversed the contraction and migration phenotypes induced by epithelial-derived exosomes. Exosomal miR-17-5p was confirmed to function as a key regulator of the phenotypic transformation of fibroblasts. In conclusion, we demonstrated that Arecoline triggers aberrant epithelium-fibroblast crosstalk and identified that epithelial cell-derived miR-17-5p mediates fibroblast differentiation through the classical TGF-β fibrotic pathway, which provided a new perspective and strategy for the diagnosis and treatment of OSF.
Topics: MicroRNAs; Oral Submucous Fibrosis; Humans; Fibroblasts; Arecoline; Epithelial Cells; Exosomes; Receptor, Transforming Growth Factor-beta Type I; Smad7 Protein; Cell Differentiation; Signal Transduction; Cell Movement; Ubiquitin-Protein Ligases; Areca
PubMed: 38897993
DOI: 10.1038/s41368-024-00302-2