Therapeutic Effects of Aß-Specific Regulatory T Cells in Alzheimer's Disease: A Study in 5xFAD Mice.

The aging global population is placing an increasing burden on healthcare systems, and the social impact of Alzheimer's disease (AD) is on the rise. However, the availability of safe and effective treatments for AD remains limited. Adoptive Treg therapy has been explored for treating neurodegenerative diseases, including AD. To facilitate the clinical application of Treg therapy, we developed a Treg preparation protocol and highlighted the therapeutic effects of Tregs in 5xFAD mice. CD4+CD25+ Tregs, isolated after Aß stimulation and expanded using a G-rex plate with a gas-permeable membrane, were adoptively transferred into 5xFAD mice. Behavioral analysis was conducted using Y-maze and passive avoidance tests. Additionally, we measured levels of Aß, phosphorylated tau (pTAU), and nitric oxide synthase 2 (NOS2) in the hippocampus. Real-time RT-PCR was employed to assess the mRNA levels of pro- and anti-inflammatory markers. Our findings indicate that Aß-specific Tregs not only improved cognitive function but also reduced Aß and pTAU accumulation in the hippocampus of 5xFAD mice. They also inhibited microglial neuroinflammation. These effects were observed at doses as low as 1.5 × 103 cells/head. Collectively, our results demonstrate that Aß-specific Tregs can mitigate AD pathology in 5xFAD mice.

Alpha-Synuclein-Specific Regulatory T Cells Ameliorate Parkinson's Disease Progression in Mice.

Parkinson's disease (PD) is a long-term neurodegenerative disease characterized by dopaminergic neuronal loss and the aggregation of alpha-synuclein (α-syn) in the brain. Cell therapy using regulatory T cells (Tregs) has therapeutic potential on PD progression in a mouse model; however, several challenges were associated with its applications. Here, we propose a strategy for α-syn specific Treg expansion (α-syn Treg). We presented α-syn to T cells via dendritic cells. This method increased the mobility of Tregs towards the site of abundant α-syn in vitro (p < 0.01; α-syn Tregs versus polyclonal Tregs (poly Tregs)) and in vivo. Consequently, α-syn Tregs showed noteworthy neuroprotective effects against motor function deficits (p < 0.05, p < 0.01; α-syn Tregs versus poly Tregs), dopaminergic neuronal loss (p < 0.001; α-syn Tregs versus poly Tregs), and α-syn accumulation (p < 0.05; α-syn Tregs versus poly Tregs) in MPTP-induced PD mice. Furthermore, the adoptive transfer of α-syn Tregs exerted immunosuppressive effects on activated microglia, especially pro-inflammatory microglia, in PD mice. Our findings suggest that α-syn presentation may provide a significant improvement in neuroprotective activities of Tregs and suggest the effective clinical application of Treg therapy in PD.

Neuroprotective effects of ex vivo-expanded regulatory T cells on trimethyltin-induced neurodegeneration in mice.

BACKGROUND: Trimethyltin (TMT) is a potent neurotoxicant that leads to hippocampal neurodegeneration. Regulatory T cells (Tregs) play an important role in maintaining the immune balance in the central nervous system (CNS), but their activities are impaired in neurodegenerative diseases. In this study, we aimed to determine whether adoptive transfer of Tregs, as a living drug, ameliorates hippocampal neurodegeneration in TMT-intoxicated mice. METHODS: CD4+CD25+ Tregs were expanded in vitro and adoptively transferred to TMT-treated mice. First, we explored the effects of Tregs on behavioral deficits using the Morris water maze and elevated plus maze tests. Biomarkers related to memory formation, such as cAMP response element-binding protein (CREB), protein kinase C (PKC), neuronal nuclear protein (NeuN), nerve growth factor (NGF), and ionized calcium binding adaptor molecule 1 (Iba1) in the hippocampus were examined by immunohistochemistry after killing the mouse. To investigate the neuroinflammatory responses, the polarization status of microglia was examined in vivo and in vitro using real-time reverse transcription polymerase chain reaction (rtPCR) and Enzyme-linked immunosorbent assay (ELISA). Additionally, the inhibitory effects of Tregs on TMT-induced microglial activation were examined using time-lapse live imaging in vitro with an activation-specific fluorescence probe, CDr20. RESULTS: Adoptive transfer of Tregs improved spatial learning and memory functions and reduced anxiety in TMT-intoxicated mice. Additionally, adoptive transfer of Tregs reduced neuronal loss and recovered the expression of neurogenesis enhancing molecules in the hippocampi of TMT-intoxicated mice. In particular, Tregs inhibited microglial activation and pro-inflammatory cytokine release in the hippocampi of TMT-intoxicated mice. The inhibitory effects of TMT were also confirmed via in vitro live time-lapse imaging in a Treg/microglia co-culture system. CONCLUSIONS: These data suggest that adoptive transfer of Tregs ameliorates disease progression in TMT-induced neurodegeneration by promoting neurogenesis and modulating microglial activation and polarization.

Targeting of adipose tissue macrophages by bee venom phospholipase A2 attenuates high-fat diet-induced obesity.

BACKGROUND/OBJECTIVES: Adipose tissue macrophages (ATMs) exist in either the M1 or M2 form. The anti-inflammatory M2 ATMs accumulate in lean individuals, whereas the pro-inflammatory M1 ATMs accumulate in obese individuals. Bee venom phospholipase A2 (bvPLA2), a major component in honeybee (Apis mellifera) venom, exerts potent anti-inflammatory effects via interactions with regulatory T cells (Treg) and macrophages. This study investigated the effects of bvPLA2 on a high-fat diet (HFD)-induced obesity in mice. SUBJECTS/METHODS: For in vivo experiments, male C57BL/6, CD206-deficient, and Treg-depleted mice models were fed either a normal diet 41.86 kJ (ND, 10 kcal% fat) or high-fat diet 251.16 kJ (HFD, 60 kcal% fat). Each group was i.p. injected with PBS or bvPLA2 (0.5 mg/kg) every 3 days for 11 weeks. Body weight and food intake were measured weekly. Histological changes in the white adipose tissue (WAT), liver, and kidney as well as the immune phenotypes of the WAT were examined. Immune cells, cytokines, and lipid profiles were also evaluated. The direct effects of bvPLA2 on 3T3-L1 pre-adipocytes and bone marrow-derived macrophages were measured in vitro. RESULTS: bvPLA2 markedly decreased bodyweight in HFD-fed mice. bvPLA2 treatment also decreased lipid accumulation in the liver and reduced kidney inflammation in the mice. It was confirmed that bvPLA2 exerted immunomodulatory effects through the CD206 receptor. In addition, bvPLA2 decreased M1 ATM and alleviated the M1/M2 imbalance in vivo. However, bvPLA2 did not directly inhibit adipogenesis in the 3T3-L1 adipose cells in vitro. CONCLUSIONS: bvPLA2 is a potential therapeutic strategy for the management of obesity by regulating adipose tissue macrophage homeostasis.

Three-year outcome of rapid HIV testing at public health centers in Seoul, Republic of Korea: a short report.

Before 2014, the only test used for anonymous voluntary human immunodeficiency virus (HIV) screening at public health centers (PHCs) in the Republic of Korea was an enzyme-linked immunosorbent assay (ELISA), which takes around 3 days to obtain results. In 2014, to encourage voluntary anonymous HIV screening tests, the Seoul Metropolitan Government adopted a rapid HIV screening test at PHCs. The rapid HIV screening test was introduced at four PHCs in 2014 and all 25 PHCs after 2015. We compared the numbers of HIV screening tests and confirmed positive individuals before and after introduction of the rapid HIV screening test. In 2012-2013, before the introduction of rapid HIV screening test, an average of 330 HIV screening tests were performed monthly (355 in 2012 and 305 in 2013) and 69 individuals were confirmed to have HIV in 2012 and 93 in 2013. After the introduction of the rapid HIV screening test, anonymous voluntary HIV screening increased to a monthly average of 447 tests in 2014, 2099 in 2015, and 2409 in 2016. These identified 38 new cases in 2014, 116 in 2015, and 143 in 2016. Adoption of the rapid HIV screening test has increased the number of HIV screening tests and confirmed cases.

8-O-(E-p-methoxycinnamoyl)harpagide Inhibits Influenza A Virus Infection by Suppressing Intracellular Calcium.

Calcium (Ca2+) dependent signaling circuit plays a critical role in influenza A virus (IAV) infection. The 8-O-(E-p-methoxycinnamoyl)harpagide (MCH) exhibits pharmacological activities that exert neuroprotective, hepatoprotective, anti-inflammatory and other biological effects. However, not have reports of antiviral effects. To investigate the antiviral activity of MCH on IAV-infected human lung cells mediated by calcium regulation. We examined the inhibitory effect of MCH on IAV infections and measured the level of viral proteins upon MCH treatment using Western blotting. We also performed molecular docking simulation with MCH and IAV M2 protein. Finally, we analyzed MCH's suppression of intracellular calcium and ROS (reactive oxygen species) in IAV-infected human lung cells using a flow cytometer. The results shown that MCH inhibited the infection of IAV and increased the survival of the infected human lung cells. The levels of IAV protein M1, M2, NS1 and PA were inhibited in MCH-treated human lung cells compared to that in infected and untreated cells. Also, docking simulation suggest that MCH interacted with M2 on its hydrophobic wall (L40 and I42) and polar amino acids (D44 and R45), which formed intermolecular contacts and were a crucial part of the channel gate along with W41. Lastly, MCH inhibited IAV infection by reducing intracellular calcium and mitochondrial Ca2+/ROS levels in infected human lung cells. Taken together, these data suggest that MCH inhibits IAV infection and increases the survival of infected human lung cells by suppressing calcium levels. These results indicate that MCH is useful for developing IAV treatments.

Ethanol extract of Chrysanthemum zawadskii Herbich induces autophagy and apoptosis in mouse colon cancer cells through the regulation of reactive oxygen species.

BACKGROUND: Recent research has suggested that autophagy can provide a better mechanism for inducing cell death than current therapeutic strategies. This study investigated the effects of using an ethanol extract of Chrysanthemum zawadskii Herbich (ECZ) to induce apoptosis and autophagy associated with reliable signal pathways in mouse colon cancer CT-26 cells. METHODS: Using ECZ on mouse colon cancer CT-26 cells, cell viability, annexin V/propidium iodide staining, acridine orange staining, reactive oxygen species (ROS) and western blotting were assayed. RESULTS: ECZ exhibited cytotoxicity in CT-26 cells in a dose-dependent manner. ECZ induced apoptosis was confirmed by caspase-3 activation, poly (ADP-ribose) polymerase cleavage, and increased production of reactive oxygen species (ROS). Furthermore, it was shown that ECZ induced autophagy via the increased conversion of microtubule-associated protein 1 light chain 3II, the degradation of p62, and the formation of acidic vesicular organelles. The inhibition of ROS production by N-Acetyl-L-cysteine resulted in reduced ECZ-induced apoptosis and autophagy. Furthermore, the inhibition of autophagy by 3-methyladenine resulted in enhanced ECZ-induced apoptosis via increased ROS generation. CONCLUSION: These findings confirmed that ECZ induced ROS-mediated autophagy and apoptosis in colon cancer cells. Therefore, ECZ may serve as a novel potential chemotherapeutic candidate for colon cancer.

Phlorotannin supplement decreases wake after sleep onset in adults with self-reported sleep disturbance: A randomized, controlled, double-blind clinical and polysomnographic study.

Our previous study demonstrated that phlorotannin supplement had a sleep-promoting effect in rodents. In the present study, we investigated whether the phlorotannin supplement could improve sleep in subjects with self-reported sleep disturbances. In a randomized, double-blind, placebo-controlled trial, 24 subjects consumed either a placebo or phlorotannin supplement (500 mg/day) for 1 week, 30-60 min prior to bedtime. Sleep parameters were assessed at baseline and at 1 week with sleep questionnaires and polysomnography. At the end of the treatment period, the complete sets of sleep parameters from 20 subjects. Phlorotannin resulted in a significant increase in "Sleep duration" scores compared to the placebo (p = .044), although there were no significant differences on the total PSQI scores. Polysomnography revealed that wakefulness after sleep onset was significantly lower in the phlorotannin group compared to the placebo group (phlorotannin vs. placebo, -25.5 ± 30.5 vs. -1.7 ± 14.9; p = .045) as well as total wake time (phlorotannin vs. placebo, -0.9 ± 3.0 vs. -6.1 ± 6.8; p = .048). Additionally, the respiratory disturbance index during supine rapid eye movement sleep was significantly lower in the phlorotannin group (p = .035). There were no serious adverse effects in either group. Our data suggest that the phlorotannin supplement improved sleep maintenance (WHO ICTRP: KCT0001892).

α-Pinene, a Major Constituent of Pine Tree Oils, Enhances Non-Rapid Eye Movement Sleep in Mice through GABAA-benzodiazepine Receptors.

α-Pinene is a major monoterpene of the pine tree essential oils. It has been reported that α-pinene shows anxiolytic and hypnotic effects upon inhaled administration. However, hypnotic effect by oral supplementation and the molecular mechanism of α-pinene have not been determined yet. By combining in vivo sleep behavior, ex vivo electrophysiological recording from brain slices, and in silico molecular modeling, we demonstrate that (-)-α-pinene shows sleep enhancing property through a direct binding to GABAA-benzodiazepine (BZD) receptors by acting as a partial modulator at the BZD binding site. The effect of (-)-α-pinene on sleep-wake profiles was evaluated by recording electroencephalogram and electromyogram. The molecular mechanism of (-)-α-pinene was investigated by electrophysiology and molecular docking study. (-)-α-pinene significantly increased the duration of non-rapid eye movement sleep (NREMS) and reduced the sleep latency by oral administration without affecting duration of rapid eye movement sleep and delta activity. (-)-α-pinene potentiated the GABAA receptor-mediated synaptic response by increasing the decay time constant of sIPSCs in hippocampal CA1 pyramidal neurons. These effects of (-)-α-pinene on sleep and inhibitory synaptic response were mimicked by zolpidem, acting as a modulator for GABAA-BZD receptors, and fully antagonized by flumazenil, an antagonist for GABAA-BZD receptor. (-)-α-pinene was found to bind to aromatic residues of α1- and -γ2 subunits of GABAA-BZD receptors in the molecular model. We conclude that (-)-α-pinene enhances the quantity of NREMS without affecting the intensity of NREMS by prolonging GABAergic synaptic transmission, acting as a partial modulator of GABAA-BZD receptors and directly binding to the BZD binding site of GABAA receptor.

Meta-analysis of the Efficacy and Safety of Secukinumab for the Treatment of Plaque Psoriasis.

BACKGROUND: In January 2015, US FDA approved secukinumab, a human interleukin-17A (IL-17A) antagonist, for the treatment of plaque psoriasis. OBJECTIVE: To provide unbiased drug information about the efficacy and safety of secukinumab for the treatment of moderate to severe plaque psoriasis by performing meta-analysis. METHODS: PubMed and EMBASE database searches were conducted. Among the literatures retrieved, relevant Phase III clinical trials were analyzed. Statistical analysis of the data was performed by RevMan. RESULTS: Four pivotal and three non-pivotal Phase III clinical trials were retrieved. All the trials evaluated the efficacy and safety of secukinumab for the treatment of moderate to severe plaque psoriasis with two co-primary endpoints: proportions of Psoriasis Area and Severity Index (PASI) responders and Investigator's Global Assessment (IGA) responders. The overall odd ratios for proportions of PASI responders and IGA responders in secukinumab-containing arm were 65.6 and 62.5 compared to the placebo arm, respectively. Secukinumab was superior to etanercept resulting in both of the odd ratios being 3.7 compared to the etanercept. Secukinumab was generally well tolerated during the one year trial. However, as with other monoclonal antibody medications, vulnerability of respiratory infection (especially nasopharyngitis) was reported as most common adverse event. CONCLUSIONS: Meta-analysis of the seven Phase III clinical trials resulted in superiority of secukinumab over etanercept in terms of the efficacy and safety. However, long-term safety data is lacking at this time so post-marketing surveillance should be performed for any adverse events associated with the use of this new biological medication.

Smartphone-based hearing screening in noisy environments.

It is important and recommended to detect hearing loss as soon as possible. If it is found early, proper treatment may help improve hearing and reduce the negative consequences of hearing loss. In this study, we developed smartphone-based hearing screening methods that can ubiquitously test hearing. However, environmental noise generally results in the loss of ear sensitivity, which causes a hearing threshold shift (HTS). To overcome this limitation in the hearing screening location, we developed a correction algorithm to reduce the HTS effect. A built-in microphone and headphone were calibrated to provide the standard units of measure. The HTSs in the presence of either white or babble noise were systematically investigated to determine the mean HTS as a function of noise level. When the hearing screening application runs, the smartphone automatically measures the environmental noise and provides the HTS value to correct the hearing threshold. A comparison to pure tone audiometry shows that this hearing screening method in the presence of noise could closely estimate the hearing threshold. We expect that the proposed ubiquitous hearing test method could be used as a simple hearing screening tool and could alert the user if they suffer from hearing loss.

Usefulness of the Rapid Antigen Test in Detecting SARS-CoV-2 for Infection Control in Hospitals.

BACKGROUND: We aimed at evaluating the diagnostic performance of rapid antigen test (RAT) compared to polymerase chain reaction (PCR) for severe acute respiratory syndrome coronavirus 2 and the possible transmission of infection to close contacts from patients with negative RAT and positive PCR results. MATERIALS AND METHODS: Patients/guardians urgently requiring admission to the ward on the same day had been hospitalized with RAT-negative result before the PCR results were available. We performed an epidemiologic investigation of the close contacts of those with negative RAT but positive PCR results after hospitalization. RESULTS: A total of 4,237 RATs were performed from March to August 2022. When the PCR test was used as the reference, RAT had a sensitivity of 28.8% (17/59; 95% confidence interval [CI], 17.8 - 42.1), a specificity of 100% (4,220/4,220; 95% CI, 99.9 - 100.0), a positive predictive value of 100.0% (17/17; 95% CI, 100.0 - 100.0), and a negative predictive value of 99.0% (4,178/4,220; 95% CI, 99.3 - 99.8). The epidemiologic investigation revealed that among the 32 patients with negative RAT and subsequent positive PCR results after admission into multi-patient room, two (6.3%) showed secondary coronavirus disease 2019. CONCLUSION: The secondary transmission rate from patients with negative RAT and positive PCR results was low. Our data suggest that RAT may be useful for rapid exclusion of high transmissible cases. However, further evaluation using whole genome sequencing is needed to determine the potential for transmissibility in cases showing a negative RAT but a positive PCR result.

Bioelectrical impedance parameters add incremental value to waist-to-hip ratio for prediction of metabolic dysfunction associated steatotic liver disease in youth with overweight and obesity.

Introduction: Metabolic dysfunction-associated steatotic liver disease (MASLD) presents a growing health concern in pediatric populations due to its association with obesity and metabolic syndrome. Bioelectrical impedance analysis (BIA) offers a non-invasive and potentially effective alternative for identifying MASLD risk in youth with overweight or obesity. Therefore, this study aimed to assess the utility of BIA for screening for MASLD in the youth. Method: This retrospective, cross-sectional study included 206 children and adolescents aged <20 years who were overweight and obese. The correlations between anthropometric measurements and BIA parameters and alanine aminotransferase (ALT) levels were assessed using Pearson's correlation analysis. Logistic regression analysis was performed to examine the associations between these parameters and ALT level elevation and MASLD score. Receiver operating characteristic (ROC) curves were generated to assess the predictive ability of the parameters for MASLD. Results: Pearson's correlation analysis revealed that waist-to-hip ratio (WHR), percentage body fat (PBF), and BIA parameters combined with anthropometric measurements were correlated with ALT level. Logistic regression revealed that WHR, skeletal muscle mass/WHR, PBF-WHR, fat-free mass/WHR, and appendicular skeletal muscle mass/WHR were correlated with ALT level elevation after adjusting for age, sex, and puberty. WHR, PBF-WHR, and visceral fat area (VFA)-WHR were positively correlated with the MASLD score in the total population after adjusting for age, sex, and puberty. PBF-WHR and VFA-WHR were correlated with the MASLD score even in youth with a normal ALT level. The cutoff points and area under the ROC curves were 34.6 and 0.69 for PBF-WHR, respectively, and 86.6 and 0.79 for VFA-WHR, respectively. Discussion: This study highlights the utility of combining BIA parameters and WHR in identifying the risk of MASLD in overweight and obese youth, even in those with a normal ALT level. BIA-based screening offers a less burdensome and more efficient alternative to conventional MASLD screening methods, facilitating early detection and intervention in youth at risk of MASLD.

Systematic Review and Meta-Analysis on Burnout Owing to Perfectionism in Elite Athletes Based on the Multidimensional Perfectionism Scale (MPS) and Athlete Burnout Questionnaire (ABQ).

Previous studies have shown that burnout negatively affects athletes' mental health. To further explore this subject, we conducted a systematic review and meta-analysis by combining data from previous studies. This study followed the PRISMA guidelines for systematic and reliable research and completed data extraction using 10 databases and 8 keywords in December 2021. There were 93 cases of initially extracted data from the selected articles (n = 14) and the meta-analysis was conducted using the "meta" package, version 4.8-4 of R Studio 3.3.3, with data (k = 77) excluding other-oriented perfectionism data (k = 16). The results showed that self-oriented perfectionism had a negative effect on sports devaluation (SD) (ESr = -0.246, p < 0.001), and socially prescribed perfectionism had a positive effect on emotional/physical exhaustion (ESr = 0.150, p < 0.05) and SD (ESr = 0.138, p < 0.05). Furthermore, the test for publication bias showed that no groups had asymmetrical data, and four moderator analyses were conducted to prove the heterogeneity (I2) of the total effect size; however, there was no difference among groups (QB), thereby resulting in unexplained variance. Consequently, this study presents variable data that determine the effects of perfectionism and burnout on elite athletes.

Active surveillance testing to reduce transmission of carbapenem-resistant, gram-negative bacteria in intensive care units: a pragmatic, randomized cross-over trial.

BACKGROUND: In intensive care unit (ICU) settings, the transmission risk of carbapenem-resistant, gram-negative bacteria (CRGNB) is high. There is a paucity of data regarding the effectiveness of interventions, including active screening, preemptive isolation, and contact precautions, to reduce transmission of CRGNB. METHODS: We conducted a pragmatic, cluster-randomized, non-blinded cross-over study in 6 adult ICUs in a tertiary care center in Seoul, South Korea. ICUs were randomly assigned to perform active surveillance testing with preemptive isolation and contact precautions (intervention) or standard precautions (control) during the initial 6-month study period, followed by a 1-month washout period. During a subsequent 6-month period, departments that used standard precautions switched to using interventional precautions and vice versa. The incidence rates of CRGNB were compared between the two periods using Poisson regression analysis. RESULTS: During the study period, there were 2268 and 2224 ICU admissions during the intervention and control periods, respectively. Because a carbapenemase-producing Enterobacterales outbreak occurred in a surgical ICU (SICU), we excluded admissions to the SICU during both the intervention and control periods and performed a modified intention-to-treat (mITT) analysis. In mITT analysis, a total of 1314 patients were included. The acquisition rate of CRGNB was 1.75 cases per 1000 person-days during the intervention period versus 3.33 cases per 1000 person-days during the control period (IRR, 0.53 [95% confidence interval (CI) 0.23-1.11]; P = 0.07). CONCLUSIONS: Although this study was underpowered and showed borderline significance, active surveillance testing and preemptive isolation could be considered in settings with high baseline prevalence of CRGNB. Trial registration Clinicaltrials.gov Identifier: NCT03980197.

Gordonia caeni sp. nov., isolated from sludge of a sewage disposal plant.

A Gram-stain-positive, strictly aerobic, short-rod-shaped, non-motile strain (designated MJ32(T)) was isolated from a sludge sample of the Daejeon sewage disposal plant in South Korea. A polyphasic approach was applied to study the taxonomic position of strain MJ32(T). Strain MJ32(T) showed highest 16S rRNA gene sequence similarity to Gordonia hirsuta DSM 44140(T) (98.1%) and Gordonia hydrophobica DSM 44015(T) (97.0%); levels of sequence similarity to the type strains of other recognized Gordonia species were less than 97.0%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain MJ32(T) belonged to the clade formed by members of the genus Gordonia in the family Gordoniaceae. The G+C content of the genomic DNA of strain MJ32(T) was 69.2 mol%. Chemotaxonomically, strain MJ32(T) showed features typical of the genus Gordonia. The predominant respiratory quinone was MK-9(H(2)), the mycolic acids present had C(56)-C(60) carbon atoms, and the major fatty acids were C(16:0) (34.6%), tuberculostearic acid (21.8%), C(16:1)ω7c (19.5%) and C(18:1)ω9c (12.7%). The peptidoglycan type was based on meso-2,6-diaminopimelic acid as the diagnostic diamino acid with glycolated sugars. On the basis of phylogenetic inference, fatty acid profile and other phenotypic properties, strain MJ32(T) is considered to represent a novel species of the genus Gordonia, for which the name Gordonia caeni sp. nov. is proposed. The type strain is MJ32(T) (=KCTC 19771(T)=JCM 16923(T)).

Hypnotic effects and GABAergic mechanism of licorice (Glycyrrhiza glabra) ethanol extract and its major flavonoid constituent glabrol.

Licorice (Glycyrrhiza glabra, GG) is one of the most frequently used herbal medicines worldwide, and its various biological activities have been widely studied. GG is reported to have neurological properties such as antidepressant, anxiolytic, and anticonvulsant effects. However, its hypnotic effects and the mechanism of GG and its active compounds have not yet been demonstrated. In this study, GG ethanol extract (GGE) dose-dependently potentiated pentobarbital-induced sleep and increased the amount of non-rapid eye movement sleep in mice without decreasing delta activity. The hypnotic effect of GGE was completely inhibited by flumazenil, which is a well-known γ-aminobutyric acid type A-benzodiazepine (GABA(A)-BZD) receptor antagonist, similar to other GABA(A)-BZD receptor agonists (e.g., diazepam and zolpidem). The major flavonoid glabrol was isolated from the flavonoid-rich fraction of GGE; it inhibited [(3)H] flumazenil binding to the GABA(A)-BZD receptors in rat cerebral cortex membrane with a binding affinity (K(i)) of 1.63 µM. The molecular structure and pharmacophore model of glabrol and liquiritigenin indicate that the isoprenyl groups of glabrol may play a key role in binding to GABA(A)-BZD receptors. Glabrol increased sleep duration and decreased sleep latency in a dose-dependent manner (5, 10, 25, and 50mg/kg); its hypnotic effect was also blocked by flumazenil. The results imply that GGE and its flavonoid glabrol induce sleep via a positive allosteric modulation of GABA(A)-BZD receptors.

Depressive effects on the central nervous system and underlying mechanism of the enzymatic extract and its phlorotannin-rich fraction from Ecklonia cava edible brown seaweed.

Marine plants have been reported to possess various pharmacological properties; however, there have been few reports on their neuropharmacological effects. Terrestrial plants have depressive effects on the central nervous system (CNS) because of their polyphenols which make them effective as anticonvulsants and sleep inducers. We investigated in this study the depressive effects of the polyphenol-rich brown seaweed, Ecklonia cava (EC), on CNS. An EC enzymatic extract (ECEE) showed significant anticonvulsive (>500 mg/kg) and sleep-inducing (>500 mg/kg) effects on the respective mice seizure induced by picrotoxin and on the mice sleep induced by pentobarbital. The phlorotannin-rich fraction (PTRF) from ECEE significantly potentiated the pentobarbital-induced sleep at >50 mg/kg. PTRF had binding activity to the gamma aminobutyric acid type A (GABA(A))-benzodiazepine (BZD) receptors. The sleep-inducing effects of diazepam (DZP, a well-known GABA(A)-BZD agonist), ECEE, and PTRF were completely blocked by flumazenil, a well-known antagonist of GABA(A)-BZD receptors. These results imply that ECEE produced depressive effects on CNS by positive allosteric modulation of its phlorotannins on GABA(A)-BZD receptors like DZP. Our study proposes EC as a candidate for the effective treatment of neuropsychiatric disorders such as anxiety and insomnia.

[Fatigue relief by aromatherapy use in prenatal and postnatal women: a systematic review and meta-analysis]. / ì•„ë¡œë§ˆí Œë¼í”¼ê°€ ì‚°ì „ 및 산후 피로에 미치는 영향: ì²´ê³„ì  ë¬¸í—Œê³ ì°° 및 메타분석.

Purpose: The purpose of this systematic review was to examine aromatherapy interventions for prenatal and postnatal women, and to determine the effectiveness of these interventions on fatigue. Methods: Six national and international databases were reviewed to retrieve and collect studies published up to September 7, 2021, describing randomized controlled trials and controlled clinical trials of aromatherapy interventions for prenatal and postnatal women's fatigue. Of the 323 articles initially identified, 64 duplicates were excluded and 259 were screened. After further excluding 216 articles not related to PICO framework, 10 were selected for review. Two reviewers independently selected studies and conducted data extraction and quality appraisal using Cochran's Risk of Bias and Risk of Bias Assessment Tool for Non-randomized Studies. Results: The quality of the 10 selected studies was overall satisfactory. A meta-analysis of three studies showed that aromatherapy with lavender oil? produced a 0.75-point reduction in postnatal mothers' fatigue when compared to control groups. Sleep quality was also analyzed as a secondary outcome of fatigue. A meta-analysis of four studies using lavender and/or orange peel oil found that aromatherapy produced a 0.98-point improvement in postnatal mothers' quality of sleep. Although a meta-analysis could not be conducted to synthesize the findings for fatigue in pregnant women, inhalation and massage therapy using lavender oil showed positive effects on prenatal fatigue and sleep quality. Conclusion: Aromatherapy using lavender oil and orange peel oil is effective in improving prenatal and postnatal fatigue and sleep quality.

[6]-Shogaol Attenuates Oxaliplatin-Induced Allodynia through Serotonergic Receptors and GABA in the Spinal Cord in Mice.

Although oxaliplatin is a well-known anti-cancer agent used for the treatment of colorectal cancer, treated patients often experience acute cold and mechanical allodynia as side effects. Unfortunately, no optimal treatment has been developed yet. In this study, [6]-shogaol (10 mg/kg, i.p.), which is one of the major bioactive components of Zingiber officinale roscoe (Z. officinale), significantly alleviated allodynia induced by oxaliplatin (6 mg/kg, i.p.) injection. Cold and mechanical allodynia were assessed by acetone drop and von Frey filament tests, respectively. The analgesic effect of [6]-shogaol was blocked by the intrathecal injection of 5-HT1A, 5-HT3, and GABAB receptor antagonists, NAN-190 (1 µg), MDL-72222 (15 µg), and CGP 55845 (10 µg), respectively. Furthermore, oxaliplatin injection lowered the GABA concentration in the superficial laminae of the spinal dorsal horn, whereas [6]-shogaol injection significantly elevated it. The GAD (glutamic acid decarboxylase) 65 concentration also increased after [6]-shogaol administration. However, pre-treatment of NAN-190 completely inhibited the increased GABA induced by [6]-shogaol in the spinal dorsal horn, whereas MDL-72222 partially blocked the effect. Altogether, these results suggest that [6]-shogaol could attenuate oxaliplatin-induced cold and mechanical allodynia through 5-HT1A and 5-HT3 receptor antagonists located in the GABAergic neurons in the spinal dorsal horn in mice.