Clinical effectiveness of music interventions for dementia and depression in elderly care (MIDDEL): Australian cohort of an international pragmatic cluster-randomised controlled trial.

BACKGROUND: Dementia and depression are highly prevalent and comorbid conditions among older adults living in care homes and are associated with individual distress and rising societal costs. Effective, scalable, and feasible interventions are needed. Music interventions have shown promising effects, but the current evidence base is inconclusive. The present study aimed to determine the effectiveness of two different music interventions on the depressive symptoms of people with dementia living in residential aged care. METHODS: We implemented a 2 × 2 factorial cluster-randomised controlled trial to determine whether group music therapy (GMT) is more effective than no GMT with standard care, or recreational choir singing (RCS) is more effective than no RCS with standard care, for reducing depressive symptoms and other secondary outcomes in people with dementia with mild to severe depressive symptoms living in residential aged care. Care home units with at least ten residents were allocated to GMT, RCS, GMT plus RCS, or standard care, using a computer-generated list with block randomisation (block size four). The protocolised interventions were delivered by music therapists (GMT) and community musicians (RCS). The primary outcome was Montgomery-Åsberg Depression Rating Scale score at 6 months, assessed by a masked assessor and analysed on an intention-to-treat basis using linear mixed-effects models, which examined the effects of GMT versus no-GMT and RCS versus no-RCS, as well as interaction effects of GMT and RCS. We report on the Australian cohort of an international trial. This trial is registered with ClinicalTrials.gov, NCT03496675, and anzctr.org.au, ACTRN12618000156280. FINDINGS: Between June 15, 2018, and Feb 18, 2020, we approached 12 RAC facilities with 26 eligible care home units and, excluding six units who could not be enrolled due to COVID-19 lockdowns, we screened 818 residents. Between July 18, 2018, and Nov 26, 2019, 20 care home units were randomised (318 residents). Recruitment ceased on March 17, 2020, due to COVID-19. The primary endpoint, available from 20 care home units (214 residents), suggested beneficial effects of RCS (mean difference -4·25, 95% CI -7·89 to -0·62; p=0·0221) but not GMT (mean difference -0·44, -4·32 to 3·43; p=0·8224). No related serious adverse events occurred. INTERPRETATION: Our study supports implementing recreational choir singing as a clinically relevant therapeutic intervention in reducing depressive symptoms for people with dementia in the Australian care home context. FUNDING: National Health and Medical Research Council, Australia.

Demographic and clinical profile of residents living with dementia and depressive symptoms in Australian private residential aged care: Data from the Music Interventions for Dementia and Depression in ELderly care (MIDDEL) cluster-randomised controlled trial.

OBJECTIVES: 1) To describe the demographic and clinical characteristics of residents with dementia and depressive symptoms in the Australian private residential aged care (RAC) context; and 2) to investigate the association between neuropsychiatric symptoms, depression and quality of life and their interactions with dementia severity. METHODS: This study examined the baseline demographic and clinical data from the Australian arm of the Music Interventions for Dementia and Depression in ELderly care (MIDDEL) study, a multinational, cluster-randomised controlled trial. Demographic characteristics, neuropsychiatric symptoms, depression, quality of life and dementia severity were collected in 330 residents of 12 private RAC facilities across Melbourne, Australia. Descriptive statistics, the Kruskal-Wallis test and the Pearson Χ2 test were used to describe and compare the demographic and clinical characteristics according to dementia severity. The association between clinical characteristics and dementia severity was examined using linear regression analyses. RESULTS: Residents' mean age was 86.5 years, 69% were female, and 44.2% had severe dementia. There were no significant differences between the dementia severity groups on age, sex and education. Residents with severe dementia were more likely to have a diagnosis of Alzheimer's disease (40.3%) and be born overseas (46.8%). Higher levels of neuropsychiatric symptoms, distress and depressive symptoms, and lower quality of life were associated with more severe dementia. CONCLUSIONS: The findings from our study highlight the diverse and complex care needs of people living with dementia in the Australian private RAC setting, which can be used to inform targeted, person-centred dementia care planning, staff training and allocation of resources.

Therapeutic music interventions with people with dementia living in residential aged care: Perspectives of residents, family members and care home staff from a cluster randomised controlled trial.

BACKGROUND: Despite growing support for the benefits of music interventions in dementia care, the perspectives of people with dementia, their families and carers are often missing from the research. This study explored multiple perspectives and first-person experiences of group music interventions delivered within a large cluster randomised controlled trial examining the effectiveness of group music therapy (GMT) and recreational choir singing (RCS) with people with dementia living in residential-aged care (RAC) settings. METHODS: Focus group and individual interviews with residents with dementia (n = 4), family members (n = 5) and care home staff (n = 15) were conducted following completion of the 6-month GMT and/or RCS intervention and analysed using inductive thematic analysis. FINDINGS: Three main themes were identified as follows: (1) direct and indirect intrapersonal benefits, (2) direct and indirect interpersonal benefits and (3) therapeutic music interventions versus entertainment. GMT and RCS supported residents' mood, enjoyment, engagement and connectedness to self and others within and post-sessions, with flow-on effects to family members, care staff and the care home environment. Participants differentiated GMT and RCS from other forms of music engagement in the RAC facilities and described feelings of post-programme loss, highlighting ongoing meaning in active therapeutic music interventions. CONCLUSION: This research highlights the need for increased access to sustainable and meaningful activities, such as purposefully designed therapeutic music interventions in RAC. Improving knowledge about the distinct benefits of therapeutic music interventions compared with other forms of music engagement in RAC may assist nursing staff to make appropriate treatment planning decisions regarding therapeutic music programmes to meet the complex needs of residents with dementia.

Exploring self-concept, wellbeing and distress in therapeutic songwriting participants following acquired brain injury: A case series analysis.

Acquired brain injury (ABI) presents a significant threat to sense of self and necessitates a complex process of psychosocial adjustment. Self-concept changes remain understudied in the early stages of inpatient rehabilitation. The aim of the current study was to examine changes in self-concept, distress, wellbeing and functional skills for five inpatients undertaking a music therapy intervention within a subacute rehabilitation centre in Victoria, Australia. Participants completed a six-week, 12-session therapeutic songwriting programme to produce past-, current- and future-self-focused songs. A range of self-concept, subjective wellbeing and distress measures were completed pre-, mid- and post-intervention. A descriptive case series approach was applied to determine trends in pre-post scores for five individual cases. Participants showing the greatest gains across self-concept and subjective wellbeing indices also showed the greatest functional gains on the Functional Independence Measure (FIM) from admission to discharge. The current study highlights the importance of examining early changes in self-concept, wellbeing and distress in subacute rehabilitation, and suggests that individualised songwriting programmes warrant further research attention in neurological populations.

Coix lacryma-jobi var. ma-yuen Stapf sprout extract induces cell cycle arrest and apoptosis in human cervical carcinoma cells.

BACKGROUND: Cervical cancer is the second-leading cause of cancer-related mortality in females. Coix lacryma-jobi L. var. ma-yuen (Rom.Caill.) Stapf ex Hook. f. is the most widely recognized medicinal herb for its remedial effects against inflammation, endocrine system dysfunctions, warts, chapped skin, rheumatism, and neuralgia and is also a nourishing food. METHODS: To investigate the activity of Coix lacryma-jobi sprout extract (CLSE) on cell proliferation in human cervical cancer HeLa cells, we conducted a Cell Counting Kit-8 (CCK-8) assay. Flow-cytometric analysis and western blot analysis were performed to verify the effect of CLSE on the regulation of the cell cycle and apoptosis in HeLa cells. RESULTS: We observed that CLSE significantly inhibited cell proliferation. Furthermore, CLSE dose-dependently promoted cell cycle arrest at the sub-G1/ S phase in HeLa cells, as detected by bromodeoxyuridine (BrdU) staining. The cell-cycle-arrest effects of CLSE in HeLa cells were associated with downregulation of cyclin D1 and cyclin-dependent kinases (CDKs) 2, 4, and 6. Moreover, CLSE induced apoptosis, as determined by flow-cytometric analysis and nuclear DNA fragmentation with Annexin V/propidium iodide (PI) and 4'6'-diamidino-2-phenylindole (DAPI) staining. Induction of apoptosis by CLSE was involved in inhibition of the antiapoptotic protein B-cell lymphoma 2 (Bcl-2) and upregulation of the apoptotic proteins p53, cleaved poly (ADP-ribose) polymerase (PARP), cleaved caspase-3, and cleaved caspase-8. Finally, we observed that CLSE inactivated the phosphoinositide 3-kinase (PI3K) and protein kinase B (AKT) pathways. CONCLUSIONS: CLSE causes cell cycle arrest and apoptotic cell death through inactivation of the PI3K/AKT pathway in HeLa cells, suggesting it is a viable therapeutic agent for cervical cancer owing to its anticancer effects.

HOMESIDE: home-based family caregiver-delivered music and reading interventions for people living with dementia: protocol of a randomised controlled trial.

INTRODUCTION: Pharmacological interventions to address behavioural and psychological symptoms of dementia (BPSD) can have undesirable side effects, therefore non-pharmacological approaches to managing symptoms may be preferable. Past studies show that music therapy can reduce BPSD, and other studies have explored how formal caregivers use music in their caring roles. However, no randomised study has examined the effects on BPSD of music interventions delivered by informal caregivers (CGs) in the home setting. Our project aims to address the need for improved informal care by training cohabiting family CGs to implement music interventions that target BPSD, and the quality of life (QoL) and well-being of people with dementia (PwD) and CGs. METHODS AND ANALYSIS: A large international three-arm parallel-group randomised controlled trial will recruit a sample of 495 dyads from Australia, Germany, UK, Poland and Norway. Dyads will be randomised equally to standard care (SC), a home-based music programme plus SC, or a home-based reading programme plus SC for 12 weeks. The primary outcome is BPSD of PwD (measured using the Neuropsychiatric Inventory-Questionnaire). Secondary outcomes will examine relationship quality between CG and PwD, depression, resilience, competence, QoL for CG and QoL for PwD. Outcomes will be collected at baseline, at the end of the 12-week intervention and at 6 months post randomisation. Resource Utilisation in Dementia will be used to collect economic data across the life of the intervention and at 6-month follow-up. We hypothesise that the music programme plus SC will generate better results than SC alone (primary comparison) and the reading programme plus SC (secondary comparison). ETHICS AND DISSEMINATION: Ethical approval has been obtained for all countries. Results will be presented at national and international conferences and published in scientific journals and disseminated to consumer and caregiver representatives and the community. TRIAL REGISTRATION NUMBERS: ACTRN12618001799246p; NCT03907748.

Music Interventions for Dementia and Depression in ELderly care (MIDDEL): protocol and statistical analysis plan for a multinational cluster-randomised trial.

INTRODUCTION: In older adults, dementia and depression are associated with individual distress and high societal costs. Music interventions such as group music therapy (GMT) and recreational choir singing (RCS) have shown promising effects, but their comparative effectiveness across clinical subgroups is unknown. This trial aims to determine effectiveness of GMT, RCS and their combination for care home residents and to examine heterogeneity of treatment effects across subgroups. METHODS AND ANALYSIS: This large, pragmatic, multinational cluster-randomised controlled trial with a 2×2 factorial design will compare the effects of GMT, RCS, both or neither, for care home residents aged 65 years or older with dementia and depressive symptoms. We will randomise 100 care home units with ≥1000 residents in total across eight countries. Each intervention will be offered for 6 months (3 months 2 times/week followed by 3 months 1 time/week), with extension allowed if locally available. The primary outcome will be the change in the Montgomery-Åsberg Depression Rating Scale score at 6 months. Secondary outcomes will include depressive symptoms, cognitive functioning, neuropsychiatric symptoms, psychotropic drug use, caregiver burden, quality of life, mortality and costs over at least 12 months. The study has 90% power to detect main effects and is also powered to determine interaction effects with gender, severity and socioeconomic status. ETHICS AND DISSEMINATION: Ethical approval has been obtained for one country and will be obtained for all countries. Results will be presented at national and international conferences and published in scientific journals. TRIAL REGISTRATION NUMBERS: NCT03496675; Pre-results, ACTRN12618000156280.

A therapeutic songwriting intervention to promote reconstruction of self-concept and enhance well-being following brain or spinal cord injury: pilot randomized controlled trial.

OBJECTIVE: To determine the size of the effects and feasibility (recruitment and retention rates) of a therapeutic songwriting protocol for in-patients and community-dwelling people with acquired brain injury or spinal cord injury. DESIGN: Randomized controlled trial with songwriting intervention and care-as-usual control groups, in a mixed measures design assessed at three time points. PARTICIPANTS: A total of 47 participants (3 in-patients with acquired brain injury, 20 community participants with acquired brain injury, 12 in-patients with spinal cord injury, and 12 community participants with spinal cord injury: 23 1208 days post injury). INTERVENTIONS: The intervention group received a 12-session identity-targeted songwriting programme, where participants created three songs reflecting on perceptions of past, present, and future self. Control participants received care as usual. MEASURES: Baseline, postintervention, and follow-up measures comprised the Head Injury Semantic Differential Scale (primary outcome measure), Patient Health Questionnaire-9, Emotion Regulation Questionnaire, and Satisfaction with Life Scale. RESULTS: No significant between group pre-post intervention differences were found on the primary self-concept measure, the Head Injury Semantic Differential Scale ( p = 0.38, d = 0.44). Significant and large effect sizes from baseline to post between groups in favour of the songwriting group for Satisfaction with Life ( p = 0.04, n2 p = 0.14). There were no significant between group pre-post interaction effects for the Emotion Regulation Suppression subscale ( p = 0.12, n2 p = -0.08) although scores decreased in the songwriting group over time while increasing for the standard care group. There were no significant differences in baseline to follow-up between groups in any other outcome measures. Recruitment was challenging due to the small number of people eligible to participate combined with poor uptake by eligible participants, particularly the in-patient group. Retention rates were higher for the community-dwelling cohorts. CONCLUSION: This study demonstrates the challenges in recruitment and retention of participants invited to participate in a music therapy study. Findings suggest this identity-focused therapeutic songwriting protocols may be more beneficial for people who have transitioned from in-patient to community-contexts given the greater proportion of participants who consent and complete the intervention. Preliminary effects in favour of the intervention group were detected in a range of well-being measures suggesting that a larger study is warranted.

Treatment Fidelity in a Music Therapy Multi-site Cluster Randomized Controlled Trial for People Living With Dementia: The MIDDEL Project Intervention Fidelity Protocol.

High-quality clinical trials testing music therapy interventions have become more prevalent over the past decade. However, recent reviews of published music therapy trials reveal that reporting of strategies used to ensure treatment fidelity is lacking. Treatment fidelity refers to methodological strategies, put in place prior to clinical trial implementation, to strengthen the reliability and validity of intervention delivery and, therefore, safeguard research quality. This paper outlines strategies developed and implemented during the pilot phase of a randomized controlled trial involving the testing of music interventions for people living with dementia and presenting with symptoms of depression. We discuss the five recognized components of fidelity (study design, training intervention providers, treatment integrity, treatment differentiation, and treatment receipt) and describe our methods for training music intervention providers and testing interventionist competence prior to trial commencement, approaches to intervention delivery supervision, and methods for assessing intervention protocol adherence.

Efficacy of Combined Treatment with Acupuncture and Bee Venom Acupuncture as an Adjunctive Treatment for Parkinson's Disease.

OBJECTIVE: The aim of this study was to evaluate the efficacy of acupuncture and bee venom acupuncture (BVA) for idiopathic Parkinson's disease (IPD) through a sham-controlled trial. We also investigated whether there is a sustained therapeutic effect by completing follow-up assessments after treatment completion. DESIGN: A single center, double-blind, three-armed randomized controlled trial. SETTINGS/LOCATION: This study was performed at a university hospital in Seoul, Republic of Korea. SUBJECTS: Seventy-three (73) patients with IPD were the subjects. They were randomly assigned to the active treatment group, sham treatment group, or conventional treatment group. INTERVENTIONS: The active treatment group received acupuncture and BVA and the sham group received sham acupuncture and normal saline injections, twice a week for 12 weeks. The conventional treatment group maintained anti-parkinsonian drugs without additional intervention. OUTCOME MEASURES: The Unified Parkinson's Disease Rating Scale (UPDRS) part II and part III score, postural instability and gait disturbance (PIGD) score, gait speed and number, Parkinson's Disease Quality of Life Questionnaire, Beck Depression Inventory, and postural stability at baseline and at 12, 16, and 20 weeks. RESULTS: Sixty-three (63) patients provided a complete data of assessments, including a final follow-up. After 12 weeks of treatment, a significant difference was observed between the active treatment group and the conventional treatment group. After the end of the treatment, the treatment effects were maintained significantly in the active treatment group only. CONCLUSIONS: It is suggested that the combined treatment of acupuncture and BVA might be safe and useful adjunctive treatment for patients with IPD.

Chamaecyparis obtusa Essential Oil Inhibits Methicillin-Resistant Staphylococcus aureus Biofilm Formation and Expression of Virulence Factors.

The emergence of antibiotic-resistant bacteria has caused difficulty in treating infectious diseases. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most commonly recognized antibiotic-resistant bacteria. Novel antibiotics are urgently required to treat these bacteria. Raw materials derived from natural sources can be used for the development of novel antibiotics, such as Chamaecyparis obtusa (C. obtusa), which has been traditionally used in treating asthmatic disease. In this study, the antibacterial activity of the essential oil (EO) extracted from C. obtusa leaves against MRSA was investigated. MRSA growth and acid production from glucose metabolism were inhibited at concentrations greater than 0.1 mg/mL C. obtusa EO. MRSA biofilm formation was observed using scanning electron microscopy and safranin staining. C. obtusa EO inhibited MRSA biofilm formation at concentrations greater than 0.1 mg/mL. Using real-time polymerase chain reaction, mRNA expression of virulence factor genes, sea, agrA, and sarA, was observed. agrA expression was inhibited with C. obtusa EO concentrations greater than 0.2 mg/mL, whereas inhibition of sea and sarA expression was also observed at a concentration of 0.3 mg/mL. C. obtusa EO was analyzed by gas chromatography (GC) and GC coupled for mass spectrometry, which identified 59 constituents, accounting to 98.99% of the total EO. These findings suggest that C. obtusa EO has antibacterial effects against MRSA, which might be associated with the major components of C. obtusa EO, such as sabinene (19.06%), α-terpinyl acetate (16.99%), bornyl acetate (10.48%), limonene (8.54%), elemol (7.47%), myrcene (5.86%), γ-terpinene (4.04%), and hibaene (3.01%).

Inhibitory Effects of Chrysanthemum boreale Essential Oil on Biofilm Formation and Virulence Factor Expression of Streptococcus mutans.

The aim of the study was to evaluate the antibacterial activity of essential oil extracted from Chrysanthemum boreale (C. boreale) on Streptococcus mutans (S. mutans). To investigate anticariogenic properties, and bacterial growth, acid production, biofilm formation, bacterial adherence of S. mutans were evaluated. Then gene expression of several virulence factors was also evaluated. C. boreale essential oil exhibited significant inhibition of bacterial growth, adherence capacity, and acid production of S. mutans at concentrations 0.1-0.5 mg/mL and 0.25-0.5 mg/mL, respectively. The safranin staining and scanning electron microscopy results showed that the biofilm formation was also inhibited. The result of live/dead staining showed the bactericidal effect. Furthermore, real-time PCR analysis showed that the gene expression of some virulence factors such as gtfB, gtfC, gtfD, gbpB, spaP, brpA, relA, and vicR of S. mutans was significantly decreased in a dose dependent manner. In GC and GC-MS analysis, seventy-two compounds were identified in the oil, representing 85.42% of the total oil. The major components were camphor (20.89%), ß-caryophyllene (5.71%), α-thujone (5.46%), piperitone (5.27%), epi-sesquiphellandrene (5.16%), α-pinene (4.97%), 1,8-cineole (4.52%), ß-pinene (4.45%), and camphene (4.19%). These results suggest that C. boreale essential oil may inhibit growth, adhesion, acid tolerance, and biofilm formation of S. mutans through the partial inhibition of several of these virulence factors.

Health benefits of kimchi (Korean fermented vegetables) as a probiotic food.

Kimchi is a traditional Korean food manufactured by fermenting vegetables with probiotic lactic acid bacteria (LAB). Many bacteria are involved in the fermentation of kimchi, but LAB become dominant while the putrefactive bacteria are suppressed during salting of baechu cabbage and the fermentation. The addition of other subingredients and formation of fermentation byproducts of LAB promote the fermentation process of LAB to eventually lead to eradication of putrefactive- and pathogenic bacteria, and also increase the functionalities of kimchi. Accordingly, kimchi can be considered a vegetable probiotic food that contributes health benefits in a similar manner as yogurt as a dairy probiotic food. Further, the major ingredients of kimchi are cruciferous vegetables; and other healthy functional foods such as garlic, ginger, red pepper powder, and so on are added to kimchi as subingredients. As all of these ingredients undergo fermentation by LAB, kimchi is regarded as a source of LAB; and the fermentative byproducts from the functional ingredients significantly boost its functionality. Because kimchi is both tasty and highly functional, it is typically served with steamed rice at every Korean meal. Health functionality of kimchi, based upon our research and that of other, includes anticancer, antiobesity, anticonstipation, colorectal health promotion, probiotic properties, cholesterol reduction, fibrolytic effect, antioxidative and antiaging properties, brain health promotion, immune promotion, and skin health promotion. In this review we describe the method of kimchi manufacture, fermentation, health functionalities of kimchi and the probiotic properties of its LAB.

Diosgenin Induces Apoptosis in HepG2 Cells through Generation of Reactive Oxygen Species and Mitochondrial Pathway.

Diosgenin, a naturally occurring steroid saponin found abundantly in legumes and yams, is a precursor of various synthetic steroidal drugs. Diosgenin is studied for the mechanism of its action in apoptotic pathway in human hepatocellular carcinoma cells. Based on DAPI staining, diosgenin-treated cells manifested nuclear shrinkage, condensation, and fragmentation. Treatment of HepG2 cells with 40 µM diosgenin resulted in activation of the caspase-3, -8, -9 and cleavage of poly-ADP-ribose polymerase (PARP) and the release of cytochrome c. In the upstream, diosgenin increased the expression of Bax, decreased the expression of Bid and Bcl-2, and augmented the Bax/Bcl-2 ratio. Diosgenin-induced, dose-dependent induction of apoptosis was accompanied by sustained phosphorylation of JNK, p38 MAPK and apoptosis signal-regulating kinase (ASK)-1, as well as generation of the ROS. NAC administration, a scavenger of ROS, reversed diosgene-induced cell death. These results suggest that diosgenin-induced apoptosis in HepG2 cells through Bcl-2 protein family-mediated mitochndria/caspase-3-dependent pathway. Also, diosgenin strongly generated ROS and this oxidative stress might induce apoptosis through activation of ASK1, which are critical upstream signals for JNK/p38 MAPK activation in HepG2 cancer cells.

Gallic acid inhibits cell viability and induces apoptosis in human monocytic cell line U937.

In the present study, we investigated the effects of gallic acid (GA) (3,4,5-trihydroxybenzoic acid), a polyhydroxyphenolic compound, isolated from Rhus chinensis, on the human monocytic lymphoma cell line U937. In vitro experiments showed that treating U937 cells with various amounts of GA inhibited cell viability and induced apoptosis in a dose-dependent manner. In order to understand the mechanism by which GA induces apoptosis, we examined the gene expression of p53, nuclear factor κB (NF-κB), and inhibitor of NF-κB (I-κB) after treating the cells with GA and found that expression levels of the genes for p53 and NF-κB increased and that for I-κB decreased. The results obtained from western blotting with U937 cells showed up-regulation of NF-κB protein and down-regulation of proliferating cell nuclear antigen and I-κB protein. These results demonstrate that GA efficiently induces apoptosis in U937 cells and that GA is a potential chemotherapeutic agent against lymphoma.

(2S)-2'-methoxykurarinone from Sophora flavescens suppresses cutaneous T cell-attracting chemokine/CCL27 expression induced by interleukin-ß/tumor necrosis factor-α via heme oxygenase-1 in human keratinocytes.

One of the CC chemokines, cutaneous T cell-attracting chemokine (CTACK/CCL27), is a skin-specific CC chemokine that is produced constitutively by keratinocytes and is highly up-regulated in inflammatory skin conditions such as atopic dermatitis and contact dermatitis. (2S)-2'-Methoxykurarinone (MOK) from Sophora flavescens has been demonstrated to have antioxidant effects. Heme oxygenase (HO)-1 has recently emerged as an important cytoprotective enzyme against oxidative stress and inflammatory responses in many cell types. This study aimed to define whether and how MOK regulates skin specific CTACK/CCL27 chemokine production in human HaCaT keratinocytes. The level of CTACK/CCL27 and HO-1 expression was measured by reverse transcription-polymerase chain reaction, and signaling was evaluated by western blot analysis. CTACK/CCL27 production was determined by enzyme-linked immunosorbent assay. Pretreatment with MOK suppressed tumor necrosis factor-α (TNF-α)- and interleukin (IL)-1ß-induced CTACK/CCL27 production in human HaCaT keratinocytes. MOK inhibited TNF-α- and IL-1ß-induced nuclear factor κB (NF-κB) activation. Interestingly, pretreatment with MOK significantly suppressed TNF-α- and IL-1ß-induced CTACK/CCL27 production through the induction of HO-1. This suppression was completely abolished by HO-1 small interfering RNA. Furthermore, carbon monoxide, but not other end products of HO-1 activity, also suppressed TNF-α- and IL-1ß-induced CTACK/CCL27 production. These results demonstrate that MOK attenuates TNF-α- and IL-1ß-induced production of CTACK/CCL27 in human HaCaT keratinocytes by inhibiting NF-κB activation and induction of HO-1.