Chronic Gut Inflammation and Dysbiosis in IBS: Unraveling Their Contribution to Atopic Dermatitis Progression.

Emerging evidence suggests a link between atopic dermatitis (AD) and gastrointestinal disorders, particularly in relation to gut microbial dysbiosis. This study explored the potential exacerbation of AD by gut inflammation and microbial imbalances using an irritable bowel syndrome (IBS) mouse model. Chronic gut inflammation was induced in the model by intrarectal injection of 2,4,6-trinitrobenzene sulfonic acid (TNBS), followed by a 4-week development period. We noted significant upregulation of proinflammatory cytokines in the colon and evident gut microbial dysbiosis in the IBS mice. Additionally, these mice exhibited impaired gut barrier function, increased permeability, and elevated systemic inflammation markers such as IL-6 and LPS. A subsequent MC903 challenge on the right cheek lasting for 7 days revealed more severe AD symptoms in IBS mice compared to controls. Further, fecal microbial transplantation (FMT) from IBS mice resulted in aggravated AD symptoms, a result similarly observed with FMT from an IBS patient. Notably, an increased abundance of Alistipes in the feces of IBS mice correlated with heightened systemic and localized inflammation in both the gut and skin. These findings collectively indicate that chronic gut inflammation and microbial dysbiosis in IBS are critical factors exacerbating AD, highlighting the integral relationship between gut and skin health.

Acupuncture attenuates comorbid anxiety- and depressive-like behaviors of atopic dermatitis through modulating neuroadaptation in the brain reward circuit in mice.

Atopic dermatitis (AD) is highly comorbid with negative emotions such as anxiety and depression. Although acupuncture has demonstrated efficacy in AD, its influence on comorbid anxiety and depression remains unclear. We sought to explore the impact and mechanisms of action of acupuncture on comorbid anxiety and depression of AD. AD-like skin lesions were induced by the topical application of MC903 to the mouse cheek. Acupuncture was performed at Gok-Ji (LI11) acupoints. AD-like phenotypes were quantified by lesion scores, scratching behavior, and histopathological changes. The effects of acupuncture on comorbid anxiety and depression-like behaviors were assessed using the elevated plus-maze (EPM), open-field tests (OFT), and tail-suspension test (TST). In addition, biochemical changes in the brain reward regions were investigated by immunoblotting for the expression of tyrosine hydroxylase (TH), dopamine D1 receptor (D1R), phospho-dopamine and cAMP-regulated phosphoprotein-32 kDa (pDARPP-32), phospho-cAMP response element binding protein (pCREB), ΔFosB, and brain-derived neurotrophic factor (BDNF) in the nucleus accumbens, dorsolateral striatum, and ventral tegmental area. Acupuncture effectively improved the chronic itching and robust AD-like skin lesions with epidermal thickening. Additionally, it considerably reduced comorbid anxiety- and depression-like symptoms, as indicated by more time spent in the open arms of the EPM and in the center of the open field and less time spent immobile in the TST. Higher pCREB, ΔFosB, BDNF, and pDARPP-32 levels, and reduced TH and D1R protein expression in the brain reward regions of AD mice were reversed by acupuncture treatment. The beneficial effects of acupuncture on clinical symptoms (scratching behavior) and comorbid psychological distress in AD strongly correlated with dorsal striatal ΔFosB levels. Collectively, these data indicate that acupuncture had a significant, positive impact on comorbid anxiety- and depression-like behaviors by modulating neuroadaptation in the brain reward circuit in mice with AD, providing a novel perspective for the non-pharmacological management of psychiatric comorbidities of AD.

Acupuncture ameliorates not only atopic dermatitis-like skin inflammation but also acute and chronic serotonergic itch possibly through blockade of 5-HT2 and 5-HT7 receptors in mice.

Acupuncture has been known to be effective for atopic dermatitis, especially ameliorating itch; however, its mechanisms are still unclear. The aim of this study was to test the anti-itch effects of acupuncture and to investigate its possible mechanisms. Acupuncture was performed at Gok-Ji (LI11) acupoints just before the injection of pruritogens in the mouse cheek model of acute itch and of MC903-induced atopic dermatitis displaying serotonergic chronic itch. Acupuncture significantly reduced acute itch triggered by compound 48/80, chloroquine, or especially serotonin. It also markedly reduced scratching behaviors evoked by the serotonin 5-HT2 receptor agonist α-methylserotonin and selective 5-HT7 receptor agonist LP 44. In addition, acupuncture treatment at LI11 had the preventive and therapeutic effects on persistent itch as well as the robust skin inflammation with epidermal thickening in mice with MC903-induced atopic dermatitis. It also considerably reduced the increased expression of 5-HT2A, 5-HT2B and 5-HT7 receptors in atopic dermatitis-like skin lesions in mice treated with MC903. Taken together, these findings highlight that acupuncture significantly ameliorates not only skin inflammation, but also acute and chronic serotonergic itch, possibly through blockade of serotonin 5-HT2 and 5-HT7 receptors.

Acupuncture inhibits neuroinflammation and gut microbial dysbiosis in a mouse model of Parkinson's disease.

Growing evidences show that gut microbiota is associated with the pathogenesis of Parkinson's disease (PD) and the gut-brain axis can be promising target for the development of the therapeutic strategies for PD. Acupuncture has been used to improve brain functions and inflammation in neurological disorders such as PD, and to recover the gastrointestinal dysfunctions in various gastrointestinal disorders. Thus, we investigated whether acupuncture could improve Parkinsonism and gut microbial dysbiosis induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. First, we observed that acupuncture treatment at acupoints GB34 and ST36 could improve motor functions and comorbid anxiety in PD mice. Next, we found that acupuncture increased the levels of dopaminergic fibers and neurons in the striatum and the substantia nigra, respectively. Acupuncture also restored the overexpression of microglia and astrocyte as well as conversion of Bax and Bcl-2 expression in both the striatum and the substantia nigra, indicating that inflammatory responses and apoptosis were blocked by acupuncture. Additionally, via 16S rRNA sequence analysis, we observed that the relative abundance of 18 genera were changed in acupuncture-treated mice compared to the PD mice. Of them, Butyricimonas, Holdemania, Frisingicoccus, Gracilibacter, Phocea, and Aestuariispira showed significant correlations with anxiety as well as motor functions. Furthermore, the predicted functional analyses showed that acupuncture restored the physiology functions such as glutathione metabolism, methane metabolism, and PD pathway. In conclusion, we suggest that the effects of acupuncture on the enhanced motor function and the protection of the dopaminergic neurons may be associated with the regulation of the gut microbial dysbiosis and thus the inhibition of the neuroinflammation in the PD mice.

Inhibitory effect of carvacrol on lipopolysaccharide-induced memory impairment in rats.

Neuroinflammation is an important process underlying a wide variety of neurodegenerative diseases. Carvacrol (CAR) is a phenolic monoterpene commonly used as a food additive due to its antibacterial properties, but it has also been shown to exhibit strong antioxidative, anti-inflammatory, and neuroprotective effects. Here, we sought to investigate the effects of CAR on inflammation in the hippocampus and prefrontal cortex, as well as the molecular mechanisms underlying these effects. In our study, lipopolysaccharide was injected into the lateral ventricle of rats to induce memory impairment and neuroinflammation. Daily administration of CAR (25, 50, and 100 mg/kg) for 21 days improved recognition, discrimination, and memory impairments relative to untreated controls. CAR administration significantly attenuated expression of several inflammatory factors in the brain, including interleukin-1ß, tumor necrosis factor-α, and cyclooxygenase-2. In addition, CAR significantly increased expression of brain-derived neurotrophic factor (BDNF) mRNA, and decreased expression of Toll-like receptor 4 (TLR4) mRNA. Taken together, these results show that CAR can improve memory impairment caused by neuroinflammation. This cognitive enhancement is due to the anti-inflammatory effects of CAR medicated by its regulation of BDNF and TLR4. Thus, CAR has significant potential as an inhibitor of memory degeneration in neurodegenerative diseases.

Water extract of Cnidii Rhizoma suppresses RANKL-induced osteoclastogenesis in RAW 264.7 cell by inhibiting NFATc1/c-Fos signaling and prevents ovariectomized bone loss in SD-rat.

BACKGROUND: Cnidii Rhizoma is the dried root stem of Cnidium officinale Makino. Cnidii Rhizoma (CR) has been used to treat menstrual irregularity, menstrual pain, and menopause in Korea. However, the effects and mechanisms of CR on RANKL-induced osteoclastogenesis pathway remain to be elucidated. In this study, we investigated the effects of CR on the inhibition of bone resorption of osteoclast and its mechanism RANK signaling pathway. METHODS: The anti-osteoclastogenesis of water extract of CR was measured using RAW 264.7 cell. Tartrate-resistant acid phosphatase (TRAP) assay, pit assay, reverse transcription polymerase chain reaction (RT-PCR) and western blot were performed. Moreover, the effects of CR were determined with an in vivo model using ovariectomized (OVX) rats. RESULTS: CR extract suppressed osteoclastogenesis, its activity and bone resorption activity through decreasing gene of osteoclast-related such as nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1), c-Fos, etc. Moreover, CR extract prevented the bone loss in OVX rats. CONCLUSION: These results show that CR has a positive effect on menopausal osteoporosis by suppressing osteoclastogenesis.

The ethanolic extract of Aralia continentalis ameliorates cognitive deficits via modifications of BDNF expression and anti-inflammatory effects in a rat model of post-traumatic stress disorder.

BACKGROUND: Post-traumatic stress disorder (PTSD) is a disease associated with that the experience of traumatic stress. The traumatic experience results in the development of a prolonged stress response that causes impaired memory function and increased inflammation in the hippocampus. Currently, antidepressants are the only approved therapy for PTSD. However, the efficacy of antidepressants in the treatment of PTSD is marginal. The ethanol extract of Aralia continentalis (AC) is traditionally used in oriental medicine, and has been showed to possess pharmacological properties, including anti-inflammatory, anti-cancer, anti-atherosclerotic, and anti-diabetic effects. Nevertheless, the effects of AC on cognitive memory and its mechanism of action in PTSD remain unclear. Given the necessity of further treatment options for PTSD, we investigated the effect of AC on the spatial cognitive impairment caused by single prolonged stress (SPS) in a rat model of PTSD. METHODS: Male rats were treated with various intraperitoneal (i.p.) doses of AC for 21 consecutive days after inducing chronic stress with the SPS procedure. RESULTS: Cognitive impairment caused by SPS were inhibited after treatment with 100 mg/kg AC, as measured by the Morris water maze test and an object recognition test. Additionally, AC treatment significantly alleviated memory-related decreases in brain-derived neurotrophic factor (BDNF) mRNA and protein levels in the hippocampus. Our results suggest that AC significantly inhibited the cognitive deficits caused by SPS via increased expression of pro-inflammatory cytokines, including tumor necrosis factor-α and interleukin-6, in the rat brain. CONCLUSIONS: AC reversed the behavioral impairments and inflammation triggered by SPS-derived traumatic stress and should be further evaluated as a potential therapeutic drug for PTSD.

Continentalic Acid Rather Than Kaurenoic Acid Is Responsible for the Anti-Arthritic Activity of Manchurian Spikenard In Vitro and In Vivo.

The aim of this study was to identify the active compound responsible for the pharmacological activities of Manchurian spikenard (Aralia continentalis Kitag.). Interleukin (IL)-1ß-stimulated human chondrocytes and monoiodoacetate (MIA)-induced osteoarthritic rats were treated with the 50% ethanolic extract of spikenard or its major components, such as continentalic acid (ent-pimara-8(14),15-diene-19-oic acid) and kaurenoic acid (ent-kaura-16-en-19-oic acid). The spikenard extract significantly inhibited IL-1ß-stimulated production of IL-6, IL-8, metalloproteinase (MMP)-1, MMP-13, cyclooxygenase (COX)-2, inducible nitric oxide synthase (iNOS) and prostaglandin(PG)E2 in a dose-dependent manner but not MMP-3 production. The extract also inhibited the IL-1ß-induced translocation of NF-κB/p65 into the nucleus and dose-dependent phosphorylation levels of extracellular signal-regulated kinase (ERK), Jun amino-terminal kinase (JNK) and p38 mitogen-activated protein (MAP) kinase. Continentalic acid exhibited significant anti-arthritic activity corresponding exactly to that of the extract containing an equivalent amount of continentalic acid. On the other hand, kaurenoic acid exhibited a compatible activity at about a 10-times higher molar concentration than that of continentalic acid. In vitro anti-arthritic activities of the spikenard extract and continentalic acid were also confirmed in MIA-induced osteoarthritic rats. The 50% ethanolic extract of Manchurian spikenard exhibited promising anti-arthritic activities in the in vitro and in vivo osteoarthritis models, and continentalic acid, not kaurenoic acid, was most probably responsible for those activities.

What intrinsic factors influence responsiveness to acupuncture in pain?: a review of pre-clinical studies that used responder analysis.

BACKGROUND: Not many studies have investigated individual sensitivity to acupuncture. To explore the intrinsic factors related to individual responses to acupuncture, we reviewed published pre-clinical studies using responder analysis on pain. METHODS: We searched the PubMed and EMBASE databases to June 2015. We included pre-clinical reports describing responders and non-responders to anti-nociceptive and analgesic effects of acupuncture in animal study. We identified the potential intrinsic factors which might be related with the response to acupuncture. RESULTS: Totally, 216 potentially relevant articles were retrieved and 14 studies met our inclusion criteria. Rat (n = 1348) and rabbit (n = 56) were used, and only electroacupuncture (EA) was applied as an intervention. Results showed that high levels of cholecystokinin-8 and receptors were associated with poor responsiveness to EA. Endogenous opioids including ß-endorphin and met-enkephalin, descending inhibitory norepinephrine and serotonin system, and hypothalamic 5'-AMP-activated protein kinase seemed to be associated with high-level responses. Spinal levels of neurotransmitters and pro-inflammatory cytokines were also differentially expressed depending on the EA sensitiveness. In the central nervous system, hypothalamus, periaqueductal grey, pituitary gland, and spinal cord were suggested to be involved in the EA responsiveness. Identified individual variations did not seem to be accidental, as the responsiveness to EA was replicated over time. However, methodological issues such as reproducibility, cut-off criteria, and clinical relevance need to be further elaborated. CONCLUSION: Our study suggests that the identification of the biological factors differentiating responders from non-responders is necessary and it may aid in understanding how acupuncture modulates pain.

Extract of Polygala tenuifolia Alleviates Stress-Exacerbated Atopy-Like Skin Dermatitis through the Modulation of Protein Kinase A and p38 Mitogen-Activated Protein Kinase Signaling Pathway.

Atopic dermatitis (AD) and stress create a vicious cycle: stress exacerbates atopic symptoms, and atopic disease elicits stress and anxiety. Targeting multiple pathways including stress and allergic inflammation is, therefore, important for treating AD. In this study, we investigated the remedial value of Polygala tenuifolia Willd. (PTW) for treating immobilization (IMO) stress-exacerbated atopy-like skin dermatitis and its underlying mechanism. Trimellitic anhydride (TMA) was applied to dorsal skin for sensitization and subsequently both ears for eliciting T-cell-dependent contact hypersensitivity in mice, which underwent 2 h-IMO stress and PTW administration for the latter 6 and 9 days in the ear exposure period of TMA, respectively. To elicit in vitro degranulation of human mast cell line-1 (HMC-1), 10 µM substance P (SP) and 200 nM corticotrophin-releasing factor (CRF) were sequentially added with 48 h-interval. PTW extract (500 µg/mL) was added 30 min before CRF treatment. IMO stress exacerbated TMA-induced scratching behavior by 252%, and increased their blood corticosterone levels by two-fold. Treatment with 250 mg/kg PTW significantly restored IMO stress-exacerbated scratching behavior and other indicators such as skin inflammation and water content, lymph node weights, and serum histamine and immunoglobulin E (lgE) levels. Furthermore, it also reversed TMA-stimulated expression of tumor necrosis factor (TNF)-α and interleukin (IL)-4 mRNAs in ear tissues. PTW significantly inhibited SP/CRF-stimulated degranulation of HMC-1 cells, subsequent tryptase secretion, and protein kinase A (PKA) activity. PTW also selectively inhibited p38 mitogen-activated protein kinase (MAPK) phosphorylation in SP/CRF-treated HMC-1 cells. PTW significantly inhibited HMC-1 cell degranulation and alleviated IMO stress-exacerbated atopic dermatitis symptoms by modulating the PKA/p38 MAPK signaling pathway.

Fucoidan improves serum lipid levels and atherosclerosis through hepatic SREBP-2-mediated regulation.

Hyperlipidemia is associated with increased risk of the development of cardiovascular diseases. Although a great deal of attention has been paid to the hypolipidemic activity of fucoidan, complex polysaccharides from brown seaweeds, the underlying mechanism is still unclear. This study was performed to investigate whether and how fucoidan has lipid-lowering potential in poloxamer-407 (P407)-induced hyperlipidemic mice. Fucoidan treatment 2 h after acute administration of P407 in these mice significantly reduced serum total cholesterol, triglycerides, and LDL cholesterol levels, but increased the levels of HDL cholesterol. In HepG2 hepatocytes and the liver, fucoidan decreased the expression of FAS and ACC mRNA with no or only a moderate inhibitory effect on SREBP-1c mRNA expression. Furthermore, fucoidan attenuated the hepatic expression of mature SREBP-2 protein with a subsequent decrease in hepatic HMG-CoA reductase mRNA expression and an increase in hepatic LDL receptor mRNA expression. In addition, atherosclerotic lesions in the aorta of chronically P407-treated mice were also reduced by fucoidan. These findings indicate that fucoidan improves serum lipid levels by regulating the expression of key enzymes of cholesterol and triglyceride syntheses in the liver through modulation of SREBP-2.

Bee venom acupuncture alleviates trimellitic anhydride-induced atopic dermatitis-like skin lesions in mice.

BACKGROUND: Bee venom acupuncture (BVA), a novel type of acupuncture therapy in which purified bee venom is injected into the specific acupuncture point on the diseased part of the body, is used primarily for relieving pain and other musculoskeletal symptoms. In the present study, therapeutic potential of BVA to improve atopic dermatitis, a representative allergic dysfunction, was evaluated in the mouse model of trimellitic anhydride (TMA)-induced skin impairment. METHODS: Mice were treated with 5% TMA on the dorsal flank for sensitization and subsequently treated with 2% TMA on the dorsum of both ears for an additional 12 days after a 3-day interval. From the 7(th) day of 2% TMA treatment, bilateral subcutaneous injection of BV (BV, 0.3 mg/kg) was performed daily at BL40 acupuncture points (located behind the knee) 1 h before 2% TMA treatment for 5 days. RESULTS: BVA treatment markedly inhibited the expression levels of both T helper cell type 1 (Th1) and Th2 cytokines in ear skin and lymph nodes of TMA-treated mice. Clinical features of AD-like symptoms such as ear skin symptom severity and thickness, inflammation, and lymph node weight were significantly alleviated by BV treatment. BV treatment also inhibited the proliferation and infiltration of T cells, the production of Th1 and Th2 cytokines, and the synthesis of interleukin (IL)-4 and immunoglobulin E (IgE)-typical allergic Th2 responses in blood. The inhibitory effect of BVA was more pronounced at BL40 acupoint than non-acupuncture point located at the base of the tail. CONCLUSIONS: These results indicate that BV injection at specific acupuncture points effectively alleviates AD-like skin lesions by inhibiting inflammatory and allergic responses in a TMA-induced contact hypersensitivity mouse model.

Effects of systemic administration of ibuprofen on stress response in a rat model of post-traumatic stress disorder.

Pro-inflammatory cytokine and brain-derived neurotrophic factor (BDNF) are modulated in post-traumatic stress disorder (PTSD). This study investigated the effects of ibuprofen (IBU) on enhanced anxiety in a rat model of PTSD induced by a single prolonged stress (SPS) procedure. The effects of IBU on inflammation and BDNF modulation in the hippocampus and the mechanisms underlying for anxiolytic action of IBU were also investigated. Male Sprague-Dawley rats were given IBU (20 or 40 mg/kg, i.p., once daily) for 14 days. Daily IBU (40 mg/kg) administration signifi cantly increased the number and duration of open arm visits in the elevated plus maze (EPM) test, reduced the anxiety index in the EPM test, and increased the time spent in the center of an open fi eld after SPS. IBU administration signifi cantly decreased the expression of pro-inflammatory mediators, such as tumor necrosis factor-α, interleukin-1ß, and BDNF, in the hippocampus, as assessed by reverse transcription-polymerase chain reaction analysis and immunohistochemistry. These fi ndings suggest that IBU exerts a therapeutic effect on PTSD that might be at least partially mediated by alleviation of anxiety symptoms due to its anti-inflammatory activity and BDNF expression in the rat brain.

Alpha-Asarone, a Major Component of Acorus gramineus, Attenuates Corticosterone-Induced Anxiety-Like Behaviours via Modulating TrkB Signaling Process.

We investigated the anxiolytic-like activity of α-asarone (AAS) from Acorus gramineus in an experimental rat model of anxiety induced by repeated administration of the exogenous stress hormone corticosterone (CORT). The putative anxiolytic effect of AAS was studied in behavioral tests of anxiety, such as the elevated plus maze (EPM) test and the hole-board test (HBT) in rats. For 21 consecutive days, male rats received 50, 100, or 200 mg/kg AAS (i.p.) 30 min prior to a daily injection of CORT. Dysregulation of the HPA axis in response to the repeated CORT injections was confirmed by measuring serum levels of CORT and the expression of corticotrophin-releasing factor (CRF) in the hypothalamus. Daily AAS (200 mg/kg) administration increased open-arm exploration significantly in the EPM test, and it increased the duration of head dipping activity in the HBT. It also blocked the increase in tyrosine hydroxylase (TH) expression in the locus coeruleus (LC) and decreased mRNA expression of brain-derived neurotrophic factor (BDNF) and its receptor, TrkB, in the hippocampus. These results indicated that the administration of AAS prior to high-dose exogenous CORT significantly improved anxiety-like behaviors, which are associated with modification of the central noradrenergic system and with BDNF function in rats. The current finding may improve understanding of the neurobiological mechanisms responsible for changes in emotions induced by repeated administration of high doses of CORT or by elevated levels of hormones associated with chronic stress. Thus, AAS did exhibit an anxiolytic-like effects in animal models of anxiety.

[The Effects of Stress Vulnerability and Parental Burnout on Mental Health in Women with Early School-Age Children during the COVID-19 Pandemic: Mediating Effect of Spirituality].

PURPOSE: This study examined the effects of stress vulnerability and parental burnout on the mental health of women with early school-aged children, with a focus on the mediating role of spirituality. METHODS: A survey was conducted among 171 women with early school-aged children in Gyeonggi Province, Gangwon Province, and Seoul. Data were collected from September to December 2022 using the Korean-Symptom Check List 95, the Parental Burnout Assessment, and the Spirituality Assessment Scale. The data were analyzed using structural equation modeling with SPSS/WIN 22.0 and AMOS 20.0. RESULTS: The study model demonstrated a good fit, explaining 40.5% of the variance in mental health through stress vulnerability, parental burnout, and spirituality. Spirituality had a significant direct impact on mental health. Additionally, participants' spirituality directly influenced their mental health, while stress vulnerability and parental burnout indirectly affected their mental health and were mediated through spirituality. CONCLUSION: Stress vulnerability and parental burnout are negatively associated with mental health, while spirituality partially mediates these effects. Implementing a program to promote spirituality is suggested to assist mothers in recognizing the value and meaning of parenting activities during nursing interventions for mental health.

Impact of Virtual Reality Mental Health Nursing Simulation on Nursing Students' Competence.

Purpose: This study investigates the impact of a Virtual Reality (VR)-based Mental Health Nursing Practice Simulation (MHNPS) on nursing students' competency in caring for individuals with mental disorders. Nursing students often face fear, anxiety, and helplessness during mental health (MH) rotations, impeding the attainment of learning objectives in the MH nursing practicum. Therefore, innovative strategies offering practice opportunities are crucial for their competence development. Methods: Using a one-group pretest-posttest repeated measures experimental design, 50 nursing students, having completed at least one MH theory course but not yet engaged in MH clinical practicum, were enrolled. Data collection occurred from October 30, 2022, to January 6, 2023. The VR simulation included six modules covering delusion, hallucination, mania, geriatric depression, adolescent depression with suicidal ideation, and obsessive-compulsive disorder. Pre-simulation questionnaires and post-simulation surveys were administered through provided links. Data were analyzed using descriptive statistics and paired t-tests to assess changes over time. Results: Immediate and sustained improvements were observed in mental disorder-related nursing knowledge, communication self-efficacy, critical thinking ability, and MH nursing clinical confidence. Attitudes toward mental illness improved significantly post-intervention (t=-2.22, p=0.031), while the problem-solving process exhibited significant enhancement six weeks later (t=3.87, p<0.001). Conclusion: The findings affirm the simulation intervention's effectiveness in enhancing nursing students' knowledge, self-efficacy, critical thinking, and confidence in MH nursing practice, with no compromise to patient safety. Integrating simulation into MH nursing practicum narrows the gap between theory and clinical practice, elevates MH care quality, and instills confidence in nursing students as professionals. Despite potential subject selection bias in this single-group pre-post intervention study, the program's comprehensive impact on knowledge, skills, and attitudes suggests opportunities for expanding psychiatric nursing practice capabilities through subsequent studies. Caution is warranted in interpreting results, but the developed program lays the groundwork for advancing nursing students' capabilities in psychiatric nursing practice.

Acupuncture ameliorates atopic dermatitis by modulating gut barrier function in a gut microbiota-dependent manner in mice.

OBJECTIVE: Atopic dermatitis (AD) is a chronic inflammatory skin disease that may be linked to changes in the gut microbiome. Acupuncture has been proven to be effective in reducing AD symptoms without serious adverse events, but its underlying mechanism is not completely understood. The purpose of this study was to investigate whether the potential effect of acupuncture on AD is gut microbiota-dependent. METHODS: AD-like skin lesions were induced by applying MC903 topically to the cheek of the mouse. Acupuncture was done at the Gok-Ji (LI11) acupoints. AD-like symptoms were assessed by lesion scores, scratching behavior, and histopathological changes; intestinal barrier function was measured by fecal output, serum lipopolysaccharide levels, histopathological changes, and mRNA expression of markers involved in intestinal permeability and inflammation. Gut microbiota was profiled using 16S rRNA gene sequencing from fecal samples. RESULTS: Acupuncture effectively improved chronic itch as well as the AD-like skin lesions with epidermal thickening, and also significantly altered gut microbiota structure as revealed by ß-diversity indices and analysis of similarities. These beneficial effects were eliminated by antibiotic depletion of gut microbiota, but were reproduced in gut microbiota-depleted mice that received a fecal microbiota transplant from acupuncture-treated mice. Interestingly, AD mice had intestinal barrier dysfunction as indicated by increased intestinal permeability, atrophy of the mucosal structure (reduced villus height and crypt depth), decreased expression of tight junctions and mucus synthesis genes, and increased expression of inflammatory mediators in the ileum. Acupuncture attenuated these abnormalities, which was gut microbiota-dependent. CONCLUSION: Acupuncture ameliorates AD-like phenotypes in a gut microbiota-dependent manner and some of these positive benefits are explained by modulation of the intestinal barrier, providing new perspective for non-pharmacological strategies for modulating gut microbiota to prevent and treat AD. Please cite this article as: Yeom M, Ahn S, Hahm DH, Jang SY, Jang SH, Park SY, Jang JH, Park J, Oh JY, Lee IS, Kim K, Kwon SK, Park HJ. Acupuncture ameliorates atopic dermatitis by modulating gut barrier function in a gut microbiota-dependent manner in mice. J Integr Med. 2024; 22(5): 600-613.

Role of gut-derived bacterial lipopolysaccharide and peripheral TLR4 in immobilization stress-induced itch aggravation in a mouse model of atopic dermatitis.

Psychological stress and intestinal leakage are key factors in atopic dermatitis (AD) recurrence and exacerbation. Here, we demonstrate the mechanism underlying bacterial translocation across intestinal epithelial barrier damaged due to stress and further aggravation of trimellitic anhydride (TMA)-induced itch, which remain unclear, in AD mice. Immobilization (IMO) stress exacerbated scratching bouts and colon histological damage, and increased serum corticosterone and lipopolysaccharide (LPS). Orally administered fluorescein isothiocyanate (FITC)-dextran and surgically injected (into the colon) Cy5.5-conjugated LPS were detected in the serum and skin after IMO stress, respectively. The relative abundance of aerobic or facultative anaerobic bacteria was increased in the colon mucus layer, and Lactobacillus murinus, E. coli, Staphylococcus nepalensis, and several strains of Bacillus sp. were isolated from the spleens and mesenteric lymph nodes. Oral antibiotics or intestinal permeability blockers, such as lubiprostone (Lu), 2,4,6-triaminopyrimidine (TAP) and ML-7, inhibited IMO stress-associated itch; however, it was reinduced through intradermal or i.p. injection of LPS without IMO stress. I.p. injection of TAK-242 (resatorvid), a TLR4 inhibitor, abrogated IMO stress-associated itch, which was also confirmed in TLR4-KO mice. IMO stress alone did not cause itch in naïve mice. IMO stress-induced itch aggravation in TMA-treated AD mice might be attributed to the translocation of gut-derived bacterial cells and LPS, which activates peripheral TLR4 signaling.

Circadian-independent cell mitosis in immortalized fibroblasts.

Two prominent timekeeping systems, the cell cycle, which controls cell division, and the circadian system, which controls 24-h rhythms of physiology and behavior, are found in nearly all living organisms. A distinct feature of circadian rhythms is that they are temperature-compensated such that the period of the rhythm remains constant (approximately 24 h) at different ambient temperatures. Even though the speed of cell division, or growth rate, is highly temperature-dependent, the cell-mitosis rhythm is temperature-compensated. Twenty-four-hour fluctuations in cell division have also been observed in numerous species, suggesting that the circadian system is regulating the timing of cell division. We tested whether the cell-cycle rhythm was coupled to the circadian system in immortalized rat-1 fibroblasts by monitoring cell-cycle gene promoter-driven luciferase activity. We found that there was no consistent phase relationship between the circadian and cell cycles, and that the cell-cycle rhythm was not temperature-compensated in rat-1 fibroblasts. These data suggest that the circadian system does not regulate the cell-mitosis rhythm in rat-1 fibroblasts. These findings are inconsistent with numerous studies that suggest that cell mitosis is regulated by the circadian system in mammalian tissues in vivo. To account for this discrepancy, we propose two possibilities: (i) There is no direct coupling between the circadian rhythm and cell cycle but the timing of cell mitosis is synchronized with the rhythmic host environment, or (ii) coupling between the circadian rhythm and cell cycle exists in normal cells but it is disconnected in immortalized cells.