Search

Atopic dermatitis (AD) is a common allergic inflammatory skin condition marked by severe itching, skin lichenification, and chronic inflammation. AD results from a complex immune response, primarily driven by T lymphocytes and environmental triggers, leading to a disrupted epidermal barrier function. Traditional treatments, such as topical corticosteroids, have limitations due to long-term side effects, highlighting the need for safer alternatives. Here, we aimed to show that Agrimonia coreana extract (ACext) can be used in treating AD-related dermatologic symptoms. ACext could inhibit CRAC (Calcium Release-Activated Calcium) channel activity, reducing Orai1/CRAC currents and decreasing intracellular calcium signaling. This inhibition was further confirmed by the reduced IL-2 levels and T cell proliferation upon ACext treatment. In a mouse model of AD, ACext significantly ameliorates symptoms, improves histological parameters, and enhances skin barrier function, demonstrating its potential for treating AD. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

This article examines the incidence of healthcare utilization for allergic and respiratory infectious diseases in children with asthma before and during the COVID-19 pandemic. The study analyzed data from the Korean Childhood Asthma Study (KAS) cohort and the Health Insurance Review and Assessment Service (HIRA) from March 2016 to March 2021. The findings showed significant decreases in hospital visits for allergic and respiratory diseases during the pandemic, with sustained reductions observed for one year. The decline in healthcare utilization may be attributed to factors such as reduced exposure to triggers and apprehension about accessing healthcare services. Further research is needed to explore the long-term effects of the pandemic on healthcare utilization. [Extracted from the article]

Calcium-activated potassium (KCa) channels are ubiquitously expressed throughout the body and are able to regulate membrane potential and intracellular calcium concentrations, thereby playing key roles in cellular physiology and signal transmission. Consequently, it is unsurprising that KCa channels have been implicated in various diseases, making them potential targets for pharmaceutical interventions. Over the past two decades, numerous studies have been conducted to develop KCa channel-targeting drugs, including those for disorders of the central and peripheral nervous, cardiovascular, and urinary systems and for cancer. In this review, we synthesize recent findings regarding the structure and activating mechanisms of KCa channels. We also discuss the role of KCa channel modulators in therapeutic medicine. Finally, we identify the major reasons behind the delay in bringing these modulators to the pharmaceutical market and propose new strategies to promote their application. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background and Objective: Preterm birth or fetal growth has been associated with reduced lung function and asthma during childhood in the general population. We aimed to elucidate whether prematurity or fetal growth has a significant influence on lung function or symptoms in children with stable asthma. Methods: We included children with stable asthma who participated in the Korean childhood Asthma Study cohort. Asthma symptoms were determined by asthma control test (ACT). Percent predicted values of pre‐ and post‐bronchodilator (BD) lung function including forced expiratory volume in 1 second (FEV1), forced vital capacity (FVC), and forced expiratory flow at 25%–75% of FVC (FEF25%–75%) were measured. Lung function and symptoms were compared according to the history of preterm birth and birth weight (BW) for gestational age (GA). Results: The study population consisted of 566 children (age range: 5–18 years). There were no significant differences in lung function and ACT between preterm and term subjects. We observed no significant difference in ACT but significant differences were observed in pre‐ and post‐BD FEV1, pre‐ and post‐BD FVC, and post‐BD FEF25%–75% according to BW for GA in total subjects. Two‐way ANOVA revealed that BW for GA rather than prematurity was a significant determining factor for pre‐ and post‐BD lung function. After regression analysis, BW for GA was still a significant determining factor of pre‐ and post‐BD FEV1 and pre‐ and post‐BD FEF25%–75%. Conclusion: Fetal growth rather than prematurity appears to have a significant effect on lung function in children with stable asthma. [ABSTRACT FROM AUTHOR]

The TRPV3 calcium ion channel is vital for maintaining skin health and has been associated with various skin-related disorders. Since TRPV3 is involved in the development of skin inflammation, inhibiting TRPV3 could be a potential treatment strategy. Alpha-mangostin isolated from Garcinia mangostana L. extract exhibits diverse positive effects on skin health; however, the underlying mechanisms remain obscure. This study investigated the TRPV3-inhibitory properties of alpha-mangostin on TRPV3 hyperactive mutants associated with Olmsted syndrome and its impact on TRPV3-induced cytokine secretion and cell death. Our findings demonstrate that alpha-mangostin effectively inhibits TRPV3, with an IC50 of 0.077 ± 0.013 μM, showing inhibitory effects on both wild-type and mutant TRPV3. TRPV3 inhibition with alpha-mangostin decreased calcium influx and cytokine release, protecting cells from TRPV3-induced death. These results indicate that alpha-mangostin reduced inflammation in TRPV3-activated skin keratinocytes, suggesting that alpha-mangostin could be potentially used for improving inflammatory skin conditions such as dermatitis. [ABSTRACT FROM AUTHOR]

Natural products are promising drug candidates with various pharmacological effects. However, they can be difficult to use due to poor bioavailability or low stability. In this experiment, while developing topical formulations containing 0.1% Agrimonia pilosa extract, a simple and rapid method of analyzing flavonoid glucuronides, which are representative ingredients, was developed and validated, and the physicochemical properties and stability of flavonoid glucuronides were observed. As a result, an optimized cream formulation was developed. The oil phase comprised tween 60, liquid paraffin, propylene glycol, cetanol, stearyl alcohol, span 60, benzyl alcohol, and A. pilosa extracts, and the water phase comprised water and citric acid hydrate. Then, physicochemical and microbial stability tests of the formulation were conducted under long-term (12 months) and accelerated conditions (6 months). It was thus confirmed that both physicochemical and biological properties were stable during the test period. Consequently, an optimized formulation for the extract was developed and stability was confirmed. [ABSTRACT FROM AUTHOR]

In this study, we aimed to develop and validate a pretreatment method for separating and analyzing the small amounts of biomarkers contained in topical cream formulations. Analyzing semisolid formulations that contain low concentrations of active ingredients is difficult. Cream formulations containing an aqueous ethanol extract of 0.1% Agrimonia pilosa is an example. Approximately 0.0013% of apigenin-7-O-glucuronide(A7OG) was contained as a biomarker in the cream. To determine the A7OG content present in the cream formulation, liquid–liquid extraction using dichlormethane was applied. In addition, the volume of the distribution liquid was measured using the peak ratios of the indicator component, A7OG, and an internal standard, baicalin. Subsequently, the A7OG content in the cream formulation was calculated. Using this time-saving method, A7OG can be simply analyzed without additional pretreatment steps, such as evaporation and reconstitution. Moreover, the validation results confirmed that this analytical method met all of the criteria. Consequently, A7OG was successfully isolated from the cream, analyzed, and quantified using the developed method. [ABSTRACT FROM AUTHOR]

Purpose: Minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) is commonly used to treat degenerative lumbar spinal disorders. It facilitates a full-scale spinal decompression and interbody fusion with minimal neural retraction using the tubular retractor system. Despite the benefits of surgical efficiency and minimalism, this technique requires a long learning curve. There is currently no consensus on the learning curve characteristics and proper training methods for MI-TLIF. Thus, this systematic review aimed to discuss the cutoff point at which technical proficiency is achieved and ways to enhance the learning process. Methods: Major databases, including PubMed, Embase, and Cochrane Library, were searched for learning curve studies that have evaluated the clinical outcome and learning progress of MI-TLIF using quantitative data. The qualities of the selected studies were assessed using the Newcastle‒Ottawa scale. The plateau points in the "learning curve" were analyzed according to various outcome measures. Results: Nine full-text articles, representing 753 cases, were included from 9743 screened studies. The most commonly used outcome measures were the operative time, followed by the complication rate. The mean cutoff point for the operative time was 31.33 ± 11.98 (range 13‒45) cases. Conclusion: The plateau point in the learning curve for MI-TLIF may differ according to the outcome measures used. Most studies have demonstrated the learning progress based on simple task efficiency, rather than patient outcomes. Moreover, the learning rate may be affected by the patients' and technical conditions. Therefore, great care is required in interpreting the learning curve and cutoff point for MI-TLIF proficiency. [ABSTRACT FROM AUTHOR]

Mouse B cells and their cell line (WEHI-231) express large-conductance background [K.sup.+] channels ([LK.sub.bg]) that are activated by arachidonic acids, characteristics similar to TREK-2. However, there is no evidence to identify the molecular nature of [LK.sub.bg]; some properties of [LK.sub.bg] were partly different from the reported results of TREK type channels. In this study, we compared the properties of cloned TREK-2 and [LK.sub.bg] in terms of their sensitivities to ATP, phosphatidylinositol 4,5-bisphosphate ([PIP.sub.2]), intracellular pH ([pH.sub.i], and membrane stretch. Similar to the previous findings of [LK.sub.bg], TREK-2 showed spontaneous activation after membrane excision (i-o patch) and were inhibited by MgATP or by [PIP.sub.2]. The inhibition by MgATP was prevented by wortmannin, suggesting membrane-delimited regulation of TREKs by phosphoinositide (PI) kinase. The same was observed with the property of [LK.sub.bg]; the activation of TREK-2 by membrane stretch was suppressed by U73122 (PLC inhibitor). As with the known properties of TREK-2, [LK.sub.bg] were activated by acidic [pH.sub.i] and inhibited by PKC activator. Finally, we confirmed the expression of TREK-2 in WEHI-231 by using RT-PCR and immunoblot analyses. The amplitude of background [K.sup.+] current and the TREK-2 expression in WEHI-231 were commonly decreased by genetic knockdown of TREK-2 using small interfering RNA. The downregulation of TREK-2 attenuated [Ca.sup.2+]-influx induced by arachidonic acid in WEHI-231. As a whole, these results strongly indicate that TREK-2 encodes [LK.sub.bg] in mouse B cells. We also newly suggest that the low activity of TREK-2 in intact cells is due to the inhibition by intrinsic [PIP.sub.2]. K2P channel; arachidonic acid; PI kinase; membrane stretch; immune cells