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Global public health is facing a major issue with emerging resistance to antimicrobial agents. Antimicrobial agents that are currently on the market are strong and efficient, but it has not been ruled out that these medications will eventually cause resistance to bacteria. Exploring novel bioactive compounds derived from natural sources is therefore, crucial to meet future demands. The present study evaluated the mode of action of the antimicrobial potential protease enzyme SH21. Protease SH21 exhibited antimicrobial activity, strong heat stability (up to 100 °C), and pH stability (pH 3.0 to 9.0). In terms of mode of action, we found that protease SH21 was able to disrupt the bacterial cell membrane as the results of the nucleotide leakage and cell membrane permeability assay. In addition, we also checked inner membrane permeability by PI uptake assay which suggested that protease SH21 has the ability to enter the bacterial cell membrane. Our results revealed that the antimicrobial protease SH21 might be a promising candidate for treating microbial infections.
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Bacillus , Pruebas de Sensibilidad Microbiana , Membrana Celular/efectos de los fármacos , Membrana Celular/metabolismo , Permeabilidad de la Membrana Celular/efectos de los fármacos , Péptido Hidrolasas/metabolismo , Concentración de Iones de Hidrógeno , Antiinfecciosos/farmacología , Antiinfecciosos/química , Antibacterianos/farmacología , Antibacterianos/química , Proteínas Bacterianas/metabolismo , Estabilidad de EnzimasRESUMEN
Our prior study reveals that the distension-contraction profiles using high-resolution manometry impedance recordings can distinguish patients with dysphagia symptom but normal esophageal function testing ("functional dysphagia") from control subjects. The aim of this study was to determine the diagnostic value of the recording protocol used in our prior studies (10-mL swallows with subjects in the Trendelenburg position) against the standard clinical protocol (5-mL swallows with subjects in the supine position). We used advanced machine learning techniques and robust metrics for classification purposes. Studies were performed on 30 healthy subjects and 30 patients with functional dysphagia. A custom-built software was used to extract the relevant distension-contraction features of esophageal peristalsis. Ensemble methods, i.e., gradient boost, support vector machines (SVMs), and logit boost, were used as the primary machine learning algorithms. Although the individual contraction features were marginally different between the two groups, the distension features of peristalsis were significantly different. The receiver operating characteristic (ROC) curve values for the standard recording protocol and the distension features ranged from 0.74 to 0.82; they were significantly better for the protocol used in our prior studies, ranging from 0.81 to 0.91. The ROC curve values using three machine learning algorithms were far superior for the distension than the contraction features of esophageal peristalsis, revealing a value of 0.95 for the SVM algorithm. Current patient classification for esophageal motility disorders, based on the contraction phase of peristalsis, ignores a large number of patients who have an abnormality in the distension phase of peristalsis. Distension-contraction plots should be the standard for assessing esophageal peristalsis in clinical practice.NEW & NOTEWORTHY Our findings underscore the superiority of distension features over contraction metrics in diagnosing esophageal dysfunctions. By leveraging state-of-the-art machine learning techniques, our study highlights the diagnostic potential of distension-contraction plots of peristalsis. Implementation of these plots could significantly enhance the accuracy of identifying patients with esophageal motor disorders, advocating for their adoption as the standard in clinical practice.
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Trastornos de Deglución , Deglución , Esófago , Manometría , Peristaltismo , Humanos , Manometría/métodos , Peristaltismo/fisiología , Masculino , Femenino , Esófago/fisiología , Esófago/fisiopatología , Persona de Mediana Edad , Adulto , Trastornos de Deglución/diagnóstico , Trastornos de Deglución/fisiopatología , Deglución/fisiología , Anciano , Inteligencia Artificial , Trastornos de la Motilidad Esofágica/diagnóstico , Trastornos de la Motilidad Esofágica/fisiopatología , Aprendizaje Automático , Contracción Muscular/fisiologíaRESUMEN
BACKGROUND: Minimizing muscle strain and reducing the risk of musculoskeletal disorders associated with intraoral scanner (IOS) usage require ergonomic awareness, device selection, and workplace adjustments in dental practice. This preliminary clinical study aimed to simulate intraoral scanning tasks using wired and wireless IOSs and assess muscle activation and fatigue for both types. MATERIALS AND METHODS: Fourteen participants performed intraoral scanning tasks using wired and wireless IOSs (i700; MEDIT), with weights of 280 g and 328 g, respectively. The same computer system and software conditions were maintained for both groups (N = 14 per IOS group). Electrodes were placed on arm, neck, and shoulder muscles, and maximal voluntary contraction (MVC) was measured. Surface electromyography (EMG) was performed during the simulation, and EMG values were normalized using MVC. The root mean square EMG (%MVC) and muscle fatigue (%) values were calculated. Statistical comparisons were performed using the Mann-Whitney U and Friedman tests, with the Bonferroni adjustment for multiple comparisons (α = 0.05). RESULTS: Arm (flexor digitorum superficialis) and neck muscles (left sternocleidomastoid and left splenius capitis) showed significantly higher EMG values with wireless IOS (P < 0.05). The neck (left sternocleidomastoid and right levator scapulae) and shoulder muscles (right trapezius descendens) demonstrated significantly higher muscle fatigue with wireless IOS (P < 0.05). CONCLUSIONS: The consecutive use of heavier wireless IOS may increase the risk of muscle activation and fatigue in certain muscles, which may have clinical implications for dentists in terms of ergonomics and musculoskeletal health.
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Electromiografía , Humanos , Masculino , Adulto , Electromiografía/métodos , Femenino , Enfermedades Musculoesqueléticas/etiología , Enfermedades Musculoesqueléticas/prevención & control , Fatiga Muscular/fisiología , Músculo Esquelético/fisiología , Músculo Esquelético/fisiopatología , Ergonomía/métodos , Adulto Joven , Contracción Muscular/fisiologíaRESUMEN
Inflammatory bowel disease (IBD) is characterized by abnormal immune responses, including elevated proinflammatory cytokines, such as tumor necrosis factor-α (TNFα) and interleukin-6 (IL-6) in the gastrointestinal (GI) tract. This study presents the synthesis and anti-inflammatory evaluation of 2,4,5-trimethylpyridin-3-ol analogues, which exhibit dual inhibition of TNFα- and IL-6-induced inflammation. Analysis using in silico methods, including 3D shape-based target identification, modeling, and docking, identified G protein-coupled estrogen receptor 1 (GPER) as the molecular target for the most effective analogue, 6-26, which exhibits remarkable efficacy in ameliorating inflammation and restoring colonic mucosal integrity. This was further validated by surface plasmon resonance (SPR) assay results, which showed direct binding to GPER, and by the results showing that GPER knockdown abolished the inhibitory effects of 6-26 on TNFα and IL-6 actions. Notably, 6-26 displayed no cytotoxicity, unlike G1 and G15, a well-known GPER agonist and an antagonist, respectively, which induced necroptosis independently of GPER. These findings suggest that the GPER-selective compound 6-26 holds promise as a therapeutic candidate for IBD.
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Enfermedades Inflamatorias del Intestino , Receptores de Estrógenos , Receptores Acoplados a Proteínas G , Receptores Acoplados a Proteínas G/antagonistas & inhibidores , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/agonistas , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/metabolismo , Humanos , Animales , Receptores de Estrógenos/metabolismo , Receptores de Estrógenos/antagonistas & inhibidores , Mucosa Intestinal/metabolismo , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/patología , Interleucina-6/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Ratones , Simulación del Acoplamiento Molecular , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Antiinflamatorios/química , Antiinflamatorios/síntesis química , Piridinas/farmacología , Piridinas/síntesis química , Piridinas/química , Piridinas/uso terapéutico , Ratones Endogámicos C57BL , Relación Estructura-ActividadRESUMEN
Recent advancements in understanding the intricate molecular mechanisms underlying immunological responses have underscored the critical involvement of ion channels in regulating calcium influx, particularly in inflammation. Nootkatone, a natural sesquiterpenoid found in Alpinia oxyphylla and various citrus species, has gained attention for its diverse pharmacological properties, including anti-inflammatory effects. This study aimed to elucidate the potential of nootkatone in modulating ion channels associated with calcium signaling, particularly CRAC, KV1.3, and KCa3.1 channels, which play pivotal roles in immune cell activation and proliferation. Using electrophysiological techniques, we demonstrated the inhibitory effects of nootkatone on CRAC, KV1.3, and KCa3.1 channels in HEK293T cells overexpressing respective channel proteins. Nootkatone exhibited dose-dependent inhibition of channel currents, with IC50 values determined for each channel. Nootkatone treatment did not significantly affect cell viability, indicating its potential safety for therapeutic applications. Furthermore, we observed that nootkatone treatment attenuated calcium influx through activated CRAC channels and showed anti-proliferative effects, suggesting its role in regulating inflammatory T cell activation. These findings highlight the potential of nootkatone as a natural compound for modulating calcium signaling pathways by targeting related key ion channels and it holds promise as a novel therapeutic agent for inflammatory disorders.
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Señalización del Calcio , Canales de Potasio de Conductancia Intermedia Activados por el Calcio , Sesquiterpenos Policíclicos , Linfocitos T , Humanos , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , Linfocitos T/inmunología , Sesquiterpenos Policíclicos/farmacología , Células HEK293 , Señalización del Calcio/efectos de los fármacos , Canales de Potasio de Conductancia Intermedia Activados por el Calcio/metabolismo , Proliferación Celular/efectos de los fármacos , Canales de Calcio Activados por la Liberación de Calcio/metabolismo , Calcio/metabolismo , Canal de Potasio Kv1.3/metabolismo , Canal de Potasio Kv1.3/antagonistas & inhibidores , Supervivencia Celular/efectos de los fármacos , Activación de Linfocitos/efectos de los fármacos , Sesquiterpenos/farmacologíaRESUMEN
Plant-derived extracellular vesicles (EVs) elicit diverse biological effects, including promoting skin health. EVs isolated from Ecklonia cava (EV-EC) carry heat shock protein 70 (HSP70), which inhibits key regulators such as TNF-α, MAPKs, and NF-κB, consequently downregulating matrix metalloproteinases (MMPs). Aging exacerbates oxidative stress, upregulating MAPK and NF-κB signaling and worsening extracellular matrix degradation in the skin. E. cava-derived phlorotannin (PT) mitigates MAPK and NF-κB signaling. We evaluated the impact of EV-EC and PT on skin rejuvenation using an in vitro keratinocyte senescence model and an in vivo aged-mouse model. Western blotting confirmed the presence of HSP70 in EV-EC. Treatment with EV-EC and PT in senescent keratinocytes increased HSP70 expression and decreased the expression of TNF-α, MAPK, NF-κB, activator protein-1 (AP-1), and MMPs. Oxidative stress was also reduced. Sequential treatment with PT and EV-EC (PT/EV-EC) yielded more significant results compared to individual treatments. The administration of PT/EV-EC to the back skin of aged mice mirrored the in vitro findings, resulting in increased collagen fiber accumulation and improved elasticity in the aged skin. Therefore, PT/EV-EC holds promise in promoting skin rejuvenation by increasing HSP70 expression, decreasing the expression of MMPs, and reducing oxidative stress in aged skin.
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Vesículas Extracelulares , Proteínas HSP70 de Choque Térmico , Queratinocitos , Estrés Oxidativo , Phaeophyceae , Rejuvenecimiento , Envejecimiento de la Piel , Piel , Animales , Vesículas Extracelulares/efectos de los fármacos , Vesículas Extracelulares/metabolismo , Phaeophyceae/química , Ratones , Envejecimiento de la Piel/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Piel/efectos de los fármacos , Piel/metabolismo , Proteínas HSP70 de Choque Térmico/metabolismo , Humanos , Estrés Oxidativo/efectos de los fármacos , Taninos/farmacología , FN-kappa B/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
BACKGROUND: Histone H3K4 tri-methylation (H3K4me3) catalyzed by Set1/COMPASS, is a prominent epigenetic mark found in promoter-proximal regions of actively transcribed genes. H3K4me3 relies on prior monoubiquitination at the histone H2B (H2Bub) by Rad6 and Bre1. Swd2/Cps35, a Set1/COMPASS component, has been proposed as a key player in facilitating H2Bub-dependent H3K4me3. However, a more comprehensive investigation regarding the relationship among Rad6, Swd2, and Set1 is required to further understand the mechanisms and functions of the H3K4 methylation. RESULTS: We investigated the genome-wide occupancy patterns of Rad6, Swd2, and Set1 under various genetic conditions, aiming to clarify the roles of Set1 and Rad6 for occupancy of Swd2. Swd2 peaks appear on both the 5' region and 3' region of genes, which are overlapped with its tightly bound two complexes, Set1 and cleavage and polyadenylation factor (CPF), respectively. In the absence of Rad6/H2Bub, Set1 predominantly localized to the 5' region of genes, while Swd2 lost all the chromatin binding. However, in the absence of Set1, Swd2 occupancy near the 5' region was impaired and rather increased in the 3' region. CONCLUSIONS: This study highlights that the catalytic activity of Rad6 is essential for all the ways of Swd2's binding to the transcribed genes and Set1 redistributes the Swd2 to the 5' region for accomplishments of H3K4me3 in the genome-wide level.
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N-Metiltransferasa de Histona-Lisina , Histonas , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Histonas/metabolismo , Histonas/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , N-Metiltransferasa de Histona-Lisina/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , Metilación , Adenosina Trifosfatasas/metabolismo , Adenosina Trifosfatasas/genética , Enzimas Ubiquitina-Conjugadoras/metabolismo , Enzimas Ubiquitina-Conjugadoras/genéticaRESUMEN
Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. FGFR4 has been implicated in HCC progression, making it a promising therapeutic target. We introduce an approach for identifying novel FGFR4 inhibitors by sequentially adding fragments to a common warhead unit. This strategy resulted in the discovery of a potent inhibitor, 4c, with an IC50 of 33 nM and high selectivity among members of the FGFR family. Although further optimisation is required, our approach demonstrated the potential for discovering potent FGFR4 inhibitors for HCC treatment, and provides a useful method for obtaining hit compounds from small fragments.
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Relación Dosis-Respuesta a Droga , Descubrimiento de Drogas , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/antagonistas & inhibidores , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/metabolismo , Humanos , Relación Estructura-Actividad , Estructura Molecular , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/química , Inhibidores de Proteínas Quinasas/síntesis química , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Proliferación Celular/efectos de los fármacos , Ensayos de Selección de Medicamentos Antitumorales , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismoRESUMEN
Background/Aims: Drugs that stabilize intestinal motility may improve the efficacy of nonabsorbable antibiotics, such as rifaximin, against small intestinal bacterial overgrowth (SIBO). We compared the efficacy of rifaximin alone with that of its combination with trimebutine maleate against SIBO. Methods: We performed a randomized double-blind placebo-controlled trial (https://cris.nih.go.kr, no. KCT0004836) that included patients with functional bloating, no constipation, and SIBO using the hydrogen (H2)-methane (CH4) glucose breath test (GBT). Patients were randomized into 2 groups in a 1:1 ratio, namely rifaximin (1200 mg/day) + trimebutine maleate (600 mg/day) group and rifaximin + placebo group, for 2 weeks. Patients completed a symptom questionnaire and underwent a GBT at baseline and at 1 month after treatment withdrawal. The primary outcome was SIBO eradication. The secondary outcomes included changes in the concentrations of exhaled gases, symptoms, and presence of adverse events. Results: The complete eradication rate of SIBO was 35.9% (14/39) in the rifaximin group, and 34.1% (14/41) in the combined group with no significant differences. In both groups, no significant differences were observed in GBT profiles before and after the treatment, respectively. However total breath H2 and CH4 concentration were conspicuously decreased in the combined group after treatment. The combined group exhibited substantial relief of bloating. The adverse events were similar in the 2 groups. Conclusion: While the combination therapy was not superior over rifaximin alone for SIBO eradication, it improves the symptom of bloating with numerically reducing the concentration of breath H2/CH4.
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OBJECTIVES: While endoscopic resection of rectal neuroendocrine tumors (NETs) has significantly increased, long-term data on risk factors for recurrence are still lacking. Our aim is to analyze the long-term outcomes of patients with rectal NETs after endoscopic resection through risk stratification. METHODS: In this multicenter retrospective study, we included patients who underwent endoscopic resection of rectal NETs from 2009 to 2018 and were followed for ≥12 months at five university hospitals. We classified the patients into three risk groups according to the clinicopathological status of the rectal neuroendocrine tumors: low, indeterminate, and high. The high-risk group was defined if the tumors have any of the followings: size ≥ 10 mm, lymphovascular invasion, muscularis propria or deeper invasion, positive resection margins, or mitotic count ≥2/10. RESULTS: A total of 346 patients were included, with 144 (41.6%), 121 (35.0%), and 81 (23.4%) classified into the low-, indeterminate-, and high-risk groups, respectively. Among the high-risk group, seven patients (8.6%) received salvage treatment 28 (27-67) days after the initial endoscopic resection, with no reported extracolonic recurrence. Throughout the follow-up period, 1.1% (4/346) of patients experienced extracolonic recurrences at 56.5 (54-73) months after the initial endoscopic resection. Three of these patients (75%) were in the high-risk group and did not undergo salvage treatment. The risk of extracolonic recurrence was significantly higher in the high-risk group compared to the other groups (p = 0.039). CONCLUSION: Physicians should be concerned about the possibility of metastasis during long-term follow-up of high-risk patients and consider salvage treatment.
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Recurrencia Local de Neoplasia , Tumores Neuroendocrinos , Neoplasias del Recto , Humanos , Estudios Retrospectivos , Neoplasias del Recto/cirugía , Neoplasias del Recto/patología , Masculino , Femenino , Persona de Mediana Edad , Tumores Neuroendocrinos/cirugía , Tumores Neuroendocrinos/patología , Anciano , Medición de Riesgo/métodos , Adulto , Factores de Riesgo , Resultado del Tratamiento , Terapia Recuperativa , Resección Endoscópica de la Mucosa , Márgenes de EscisiónRESUMEN
Chemotherapy combined with debulking surgery is the standard treatment protocol for high-grade serous ovarian carcinoma (HGSOC). Nonetheless, a significant number of patients encounter relapse due to the development of chemotherapy resistance. To better understand and address this resistance, we conducted a comprehensive study investigating the transcriptional alterations at the single-cell resolution in tissue samples from patients with HGSOC, using single-cell RNA sequencing and T-cell receptor sequencing techniques. Our analyses unveiled notable changes in the tumor signatures after chemotherapy, including those associated with epithelial-mesenchymal transition and cell cycle arrest. Within the immune compartment, we observed alterations in the T-cell profiles, characterized by naïve or pre-exhausted populations following chemotherapy. This phenotypic change was further supported by the examination of adjoining T-cell receptor clonotypes in paired longitudinal samples. These findings underscore the profound impact of chemotherapy on reshaping the tumor landscape and the immune microenvironment. This knowledge may provide clues for the development of future therapeutic strategies to combat treatment resistance in HGSOC.
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Neoplasias Ováricas , Femenino , Humanos , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/genética , Neoplasias Ováricas/patología , Recurrencia Local de Neoplasia/tratamiento farmacológico , Recurrencia Local de Neoplasia/genética , Linfocitos T/patología , Receptores de Antígenos de Linfocitos T , Microambiente TumoralRESUMEN
Although countless gut microbiome studies on colitis using mouse models have been carried out, experiments with small sample sizes have encountered reproducibility limitations because of batch effects and statistical errors. In this study, dextran-sodium-sulfate-induced microbial dysbiosis index (DiMDI) was introduced as a reliable dysbiosis index that can be used to assess the state of microbial dysbiosis in DSS-induced mouse models. Meta-analysis of 189 datasets from 11 independent studies was performed to construct the DiMDI. Microbial dysbiosis biomarkers, Muribaculaceae, Alistipes, Turicibacter, and Bacteroides, were selected through four different feature selection methods and used to construct the DiMDI. This index demonstrated a high accuracy of 82.3% and showed strong robustness (88.9%) in the independent cohort. Therefore, DiMDI may be used as a standard for assessing microbial imbalance in DSS-induced mouse models and may contribute to the development of reliable colitis microbiome studies in mouse experiments.
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DddA-derived cytosine base editors (DdCBEs) and transcription activator-like effector (TALE)-linked deaminases (TALEDs) catalyze targeted base editing of mitochondrial DNA (mtDNA) in eukaryotic cells, a method useful for modeling of mitochondrial genetic disorders and developing novel therapeutic modalities. Here, we report that A-to-G-editing TALEDs but not C-to-T-editing DdCBEs induce tens of thousands of transcriptome-wide off-target edits in human cells. To avoid these unwanted RNA edits, we engineered the substrate-binding site in TadA8e, the deoxy-adenine deaminase in TALEDs, and created TALED variants with fine-tuned deaminase activity. Our engineered TALED variants not only reduced RNA off-target edits by >99% but also minimized off-target mtDNA mutations and bystander edits at a target site. Unlike wild-type versions, our TALED variants were not cytotoxic and did not cause developmental arrest of mouse embryos. As a result, we obtained mice with pathogenic mtDNA mutations, associated with Leigh syndrome, which showed reduced heart rates.
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ADN Mitocondrial , Efectores Tipo Activadores de la Transcripción , Animales , Humanos , Ratones , Adenina , Citosina , ADN Mitocondrial/genética , Edición Génica , ARN , Efectores Tipo Activadores de la Transcripción/metabolismo , Ingeniería de ProteínasRESUMEN
In this study, the optimal fabrication parameters of a heterogeneous anion-exchange membrane (AEM) using an ionomer binder are investigated to improve the performance of continuous electrodeionization (CEDI) for producing ultrapure water. Poly(2,6-dimethyl-1,4-phenylene oxide) (PPO) is selected as the base material for preparing the ionomer binder and quaternized to have various ion exchange capacities (IECs). The optimal content of ion-exchange resin (IER) powder according to the IEC of the ionomer binder is then determined through systematic analyses. In conclusion, it is revealed that a heterogeneous AEM with optimal performance can be fabricated when the IEC of the ionomer binder is lowered and the content of IER powder is also lower than that of conventional heterogeneous membranes. Moreover, crosslinked quaternized PPO (QPPO) nanofiber powder is used as an additive to improve ion conductivity without deteriorating the mechanical properties of the membrane. The membrane fabricated under optimal conditions exhibits significantly lower electrical resistance (4.6 Ω cm2) despite a low IER content (30 wt%) compared to the commercial membrane (IONAC MA-3475, 13.6 Ω cm2) while also demonstrating moderate tensile strength (9.7 MPa) and a high transport number (ca. 0.97). Furthermore, it is proven that the prepared membrane exhibits a superior ion removal rate (99.86%) and lower energy consumption (0.35 kWh) compared to the commercial membrane (99.76% and 0.4 kWh, respectively) in CEDI experiments.
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Agrimonia pilosa Ledeb., an important medicinal herb in traditional East Asian medicine, is primarily used to treat abdominal pain, dysentery, and hemostasis. There are ten other reported species of Agrimonia plants, including Agrimonia coreana Nakai-a naturally growing species in South Korea-and Agrimonia eupatoria Linn. Although recent studies have isolated numerous active constituents and investigated their effects, the medicinal utility of this herb is not yet fully explored. Through patch-clamp recording, a previous study reported that Agrimonia plant extracts inhibit the function of Ca2+ release-activated Ca2+ channels (CRACs). Herein, we aimed to identify and isolate the main compounds in A. coreana responsible for CRAC inhibition while assessing the anti-inflammatory effects mediated by this inhibition. We demonstrated for the first time that alphitolic acid isolated from A. coreana has a dose-dependent inhibitory effect on CRAC activity and, thus, an inhibitory effect on intracellular calcium increase. Furthermore, analysis of human CD4+ T cell proliferation via the carboxyfluorescein diacetate succinimidyl ester method revealed that alphitolic acid inhibited T cell proliferation in a concentration-dependent manner. Our findings provide a theoretical basis for the potential therapeutic use of alphitolic acid in the treatment of inflammatory diseases.
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Agrimonia , Humanos , Linfocitos T , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Antiinflamatorios/farmacologíaRESUMEN
The use of laboratory animals in biomedical research has significantly advanced scientific understanding, yet it raises ethical concerns about animal welfare and the mental health of researchers Recent research has highlighted the potential for stress and compassion fatigue among researchers working with distressed animals. Attending veterinarians (AVs) are crucial in mitigating the pain and stress experienced by animals and, by extension, researchers. However, the impact of AVs on researchers' psychological well-being remains understudied. This study explores how AVs contribute to researchers' research capability and psychological well-being in animal research institutions. AVs oversee animal housing, health, and welfare; their involvement is mandated or strongly recommended in developed countries. AVs enhance animal welfare by ensuring proper housing, nutrition, and social interaction. They monitor animal health, educate researchers on pain assessment, and promote compliance with post-surgical care. AVs also contribute to researchers' well-being by addressing euthanasia procedures, which can be emotionally challenging. Programs for rehoming animals after experiments offer an alternative to euthanasia and positively impact researchers' psychological well-being. Moreover, AVs promote workplace well-being by fostering positive workplace cultures, offering peer counseling, and providing social support. Programs considering animal welfare and researchers' emotions are crucial for a healthy research environment. In conclusion, AVs are essential in balancing scientific progress with animal welfare and researchers' psychological well-being. Therefore, their role should be recognized as vital in achieving social equity that considers the welfare of humans and laboratory animals.
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Background and aim: prokinetics could eradicate small intestinal bacterial overgrowth. This study aimed to evaluate the efficacy of mosapride, rifaximin and a combination of mosapride and rifaximin for the treatment of small intestinal bacterial overgrowth. Methods: we randomly assigned patients with functional dyspepsia diagnosed with small intestinal bacterial overgrowth in a 1:1:1 ratio to receive mosapride, rifaximin or a combination of both for two weeks. The hydrogen-methane glucose breath test and symptom questionnaire were surveyed before and after the treatment. Primary outcome was eradication rate of small intestinal bacterial overgrowth. Secondary outcomes were changes in the gas concentration, symptoms and safety. Results: the eradication rates were 17.2 % (5/29) for mosapride, 32.1 % (9/28) for rifaximin, and 34.6 % (9/26) for the combined groups, with no significant differences among the three groups. Total hydrogen concentration during the glucose breath test significantly decreased in the rifaximin group (p = 0.001). Total methane concentration significantly decreased in the rifaximin and combined groups (p = 0.005). Significant symptomatic improvements were observed in chest and abdominal discomfort with mosapride, in flatulence with rifaximin, and in chest discomfort with the combined groups. Adverse events were similar between the groups. Conclusions: rifaximin has an advantage of reducing gas, whereas mosapride can help to decrease breath hydrogen concentration. Certain intestinal symptoms improved with mosapride alone or combined with rifaximin (AU)
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Humanos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Rifaximina/uso terapéutico , Dispepsia/diagnóstico , Dispepsia/tratamiento farmacológico , Fármacos Gastrointestinales/uso terapéutico , Pruebas Respiratorias , Estudios ProspectivosRESUMEN
Objectives: Rectocele with constipation might be related to methane (CH4) producing intestinal bacteria. We investigated the breath CH4 levels and the clinical characteristics of colorectal motility in constipated patients with rectocele. Methods: A database of consecutive female outpatients was reviewed for the evaluation of constipation according to the Rome III criteria. The patients underwent the lactulose CH4 breath test (LMBT), colon marker study, anorectal manometry, defecography and bowel symptom questionnaire. The profiles of the lactulose breath test (LBT) in 33 patients with rectocele (with size ≥ 2 cm) and 26 patients with functional constipation (FC) were compared with the breath test results of 30 healthy control subjects. Results: The mean size of rectocele was 3.52 ± 1.06 cm. The rate of a positive LMBT (LMBT+) was significantly higher in patients with rectocele (33.3%) than in those with FC (23.1%) or healthy controls (6.7%) (p = 0.04). Breath CH4 concentration was positively correlated with rectosigmoid colon transit time in rectocele patients (γ = 0.481, p < 0.01). A maximum high pressure zone pressure > 155 mmHg was a significant independent factor of LMBT+ in rectocele patients (OR = 8.93, 95% CI = 1.14-71.4, p = 0.04). Conclusions: LMBT+ might be expected in constipated patients with rectocele. Moreover, increased rectosigmoid colonic transit or high anorectal pressure might be associated with CH4 breath levels. Breath CH4 could be an important therapeutic target for managing constipated patients with rectocele (AU)
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