Etomoxir, a carnitine palmitoyltransferase 1 inhibitor, combined with temozolomide reduces stemness and invasiveness in patient-derived glioblastoma tumorspheres.

INTRODUCTION: The importance of fatty acid oxidation (FAO) in the bioenergetics of glioblastoma (GBM) is being realized. Etomoxir (ETO), a carnitine palmitoyltransferase 1 (CPT1) inhibitor exerts cytotoxic effects in GBM, which involve interrupting the FAO pathway. We hypothesized that FAO inhibition could affect the outcomes of current standard temozolomide (TMZ) chemotherapy against GBM. METHODS: The FAO-related gene expression was compared between GBM and the tumor-free cortex. Using four different GBM tumorspheres (TSs), the effects of ETO and/or TMZ was analyzed on cell viability, tricarboxylate (TCA) cycle intermediates and adenosine triphosphate (ATP) production to assess metabolic changes. Alterations in tumor stemness, invasiveness, and associated transcriptional changes were also measured. Mouse orthotopic xenograft model was used to elucidate the combinatory effect of TMZ and ETO. RESULTS: GBM tissues exhibited overexpression of FAO-related genes, especially CPT1A, compared to the tumor-free cortex. The combined use of ETO and TMZ further inhibited TCA cycle and ATP production than single uses. This combination treatment showed superior suppression effects compared to treatment with individual agents on the viability, stemness, and invasiveness of GBM TSs, as well as better downregulation of FAO-related gene expression. The results of in vivo study showed prolonged survival outcomes in the combination treatment group. CONCLUSION: ETO, an FAO inhibitor, causes a lethal energy reduction in the GBM TSs. When used in combination with TMZ, ETO effectively reduces GBM cell stemness and invasiveness and further improves survival. These results suggest a potential novel treatment option for GBM.

Dual inhibition of CPT1A and G6PD suppresses glioblastoma tumorspheres.

PURPOSE: Limited treatment options are currently available for glioblastoma (GBM), an extremely lethal type of brain cancer. For a variety of tumor types, bioenergetic deprivation through inhibition of cancer-specific metabolic pathways has proven to be an effective therapeutic strategy. Here, we evaluated the therapeutic effects and underlying mechanisms of dual inhibition of carnitine palmitoyltransferase 1A (CPT1A) and glucose-6-phosphate dehydrogenase (G6PD) critical for fatty acid oxidation (FAO) and the pentose phosphate pathway (PPP), respectively, against GBM tumorspheres (TSs). METHODS: Therapeutic efficacy against GBM TSs was determined by assessing cell viability, neurosphere formation, and 3D invasion. Liquid chromatography-mass spectrometry (LC-MS) and RNA sequencing were employed for metabolite and gene expression profiling, respectively. Anticancer efficacy in vivo was examined using an orthotopic xenograft model. RESULTS: CPT1A and G6PD were highly expressed in GBM tumor tissues. Notably, siRNA-mediated knockdown of both genes led to reduced viability, ATP levels, and expression of genes associated with stemness and invasiveness. Similar results were obtained upon combined treatment with etomoxir and dehydroepiandrosterone (DHEA). Transcriptome analyses further confirmed these results. Data from LC-MS analysis showed that this treatment regimen induced a considerable reduction in the levels of metabolites associated with the TCA cycle and PPP. Additionally, the combination of etomoxir and DHEA inhibited tumor growth and extended survival in orthotopic xenograft model mice. CONCLUSION: Our collective findings support the utility of dual suppression of CPT1A and G6PD with selective inhibitors, etomoxir and DHEA, as an efficacious therapeutic approach for GBM.

Exosome-based delivery of super-repressor IκBα ameliorates kidney ischemia-reperfusion injury.

Ischemia-reperfusion injury is a major cause of acute kidney injury. Recent studies on the pathophysiology of ischemia-reperfusion-induced acute kidney injury showed that immunologic responses significantly affect kidney ischemia-reperfusion injury and repair. Nuclear factor (NF)-ĸB signaling, which controls cytokine production and cell survival, is significantly involved in ischemia-reperfusion-induced acute kidney injury, and its inhibition can ameliorate ischemic acute kidney injury. Using EXPLOR, a novel, optogenetically engineered exosome technology, we successfully delivered the exosomal super-repressor inhibitor of NF-ĸB (Exo-srIĸB) into B6 wild type mice before/after kidney ischemia-reperfusion surgery, and compared outcomes with those of a control exosome (Exo-Naïve)-injected group. Exo-srIĸB treatment resulted in lower levels of serum blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin in post-ischemic mice than in the Exo-Naïve treatment group. Systemic delivery of Exo-srIĸB decreased NF-ĸB activity in post-ischemic kidneys and reduced apoptosis. Post-ischemic kidneys showed decreased gene expression of pro-inflammatory cytokines and adhesion molecules with Exo-srIĸB treatment as compared with the control. Intravital imaging confirmed the uptake of exosomes in neutrophils and macrophages. Exo-srIĸB treatment also significantly affected post-ischemic kidney immune cell populations, lowering neutrophil, monocyte/macrophage, and T cell frequencies than those in the control. Thus, modulation of NF-ĸB signaling through exosomal delivery can be used as a novel therapeutic method for ischemia-reperfusion-induced acute kidney injury.

Tissue-specific biomarkers in gingival crevicular fluid are correlated with external root resorption caused by constant mechanical load: an in vivo study.

OBJECTIVES: This study investigated the association of changes in cementum protein-1 (CEMP-1), dentine phosphoprotein (DPP), and c-terminal cross-linked telopeptide of type I collagen (CTX-I) levels in human gingival crevicular fluid (GCF) under constant load with external root resorption volume and amount of tooth movement. MATERIALS AND METHODS: In total, 11 healthy adult patients (mean age, 23.5 years [range, 18.3-37.7]; four men and seven women) were enrolled. GCF samples were obtained from premolars at T0, T1 (1 day), T2 (1 week), T3 (2 weeks), T4 (4 weeks), and T5 (8 weeks) under constant 100-gm buccal tipping force. Opposite premolars were used as controls. Teeth were extracted at T5, followed by quantification of external root resorption volume and histological analysis. RESULTS: In the test group, T5/T0 ratios of CEMP-1 and DPP levels, differential CEMP-1 levels between T5 and T0, and differential DPP levels between T2 and T0 correlated positively with root resorption volume (r = 0.734, 0.730, 0.627, and 0.612, respectively, all p < 0.05). CEMP-1 levels at T0 and T3 correlated negatively with root resorption volume (r = -0.603 and -0.706; all p < 0.05). CTX-I levels at T5 correlated positively with the amount of tooth movement (r = 0.848, p < 0.01). CONCLUSIONS: Alterations in CEMP-1 and DPP levels in human GCF at specific timepoints during orthodontic treatment may be associated with different degrees of external root resorption. CLINICAL RELEVANCE: This study demonstrates that changes in the levels of tissue-specific biomarkers in GCF may facilitate early detection of external root resorption during orthodontic tooth movement.

Competing Endogenous RNA of Snail and Zeb1 UTR in Therapeutic Resistance of Colorectal Cancer.

The epithelial-mesenchymal transition (EMT) comprises an important biological mechanism not only for cancer progression but also in the therapeutic resistance of cancer cells. While the importance of the protein abundance of EMT-inducers, such as Snail (SNAI1) and Zeb1 (ZEB1), during EMT progression is clear, the reciprocal interactions between the untranslated regions (UTRs) of EMT-inducers via a competing endogenous RNA (ceRNA) network have received little attention. In this study, we found a synchronized transcript abundance of Snail and Zeb1 mediated by a non-coding RNA network in colorectal cancer (CRC). Importantly, the trans-regulatory ceRNA network in the UTRs of EMT inducers is mediated by competition between tumor suppressive miRNA-34 (miR-34) and miRNA-200 (miR-200). Furthermore, the ceRNA network consisting of the UTRs of EMT inducers and tumor suppressive miRs is functional in the EMT phenotype and therapeutic resistance of colon cancer. In The Cancer Genome Atlas (TCGA) samples, we also found genome-wide ceRNA gene sets regulated by miR-34a and miR-200 in colorectal cancer. These results indicate that the ceRNA networks regulated by the reciprocal interaction between EMT gene UTRs and tumor suppressive miRs are functional in CRC progression and therapeutic resistance.

Prediction of African Swine Fever Virus Inhibitors by Molecular Docking-Driven Machine Learning Models.

African swine fever virus (ASFV) causes a highly contagious and severe hemorrhagic viral disease with high mortality in domestic pigs of all ages. Although the virus is harmless to humans, the ongoing ASFV epidemic could have severe economic consequences for global food security. Recent studies have found a few antiviral agents that can inhibit ASFV infections. However, currently, there are no vaccines or antiviral drugs. Hence, there is an urgent need to identify new drugs to treat ASFV. Based on the structural information data on the targets of ASFV, we used molecular docking and machine learning models to identify novel antiviral agents. We confirmed that compounds with high affinity present in the region of interest belonged to subsets in the chemical space using principal component analysis and k-means clustering in molecular docking studies of FDA-approved drugs. These methods predicted pentagastrin as a potential antiviral drug against ASFVs. Finally, it was also observed that the compound had an inhibitory effect on AsfvPolX activity. Results from the present study suggest that molecular docking and machine learning models can play an important role in identifying potential antiviral drugs against ASFVs.

Effect of a group music intervention on cognitive function and mental health outcomes among nursing home residents: A randomized controlled pilot study.

The purpose of this study was to determine the effect of a group music intervention with rhythmic exercises program on cognitive function and mental health outcomes among Korean nursing home residents . A randomized controlled study design was employed, in which the experimental group (n = 20) received a biweekly group music intervention with rhythmic exercises program and a regular activities program for 12 weeks, and the control group (n = 20) received only a regular activities program provided by the nursing home. We measured cognitive function and mental health outcomes using the Mini-Mental State Examination-Korean Version (MMSE-K), Geriatric Depression Scale Short Form-Korean Version (GDSSF-K), Geriatric Anxiety Inventory-Korean Version (GAI-K), and Life Satisfaction Scale. ANCOVA was performed to examine the effect of the group music intervention on the study variables. The results suggested that the group music intervention with rhythmic exercises program improved cognitive function, depression, anxiety, and life satisfaction.

Newly designed Protein Transduction Domain (PTD)-mediated BMP-7 is a potential therapeutic for peritoneal fibrosis.

While the bone morphogenetic protein-7 (BMP-7) is a well-known therapeutic growth factor reverting many fibrotic diseases, including peritoneal fibrosis by peritoneal dialysis (PD), soluble growth factors are largely limited in clinical applications owing to their short half-life in clinical settings. Recently, we developed a novel drug delivery model using protein transduction domains (PTD) overcoming limitation of soluble recombinant proteins, including bone morphogenetic protein-7 (BMP-7). This study aims at evaluating the therapeutic effects of PTD-BMP-7 consisted of PTD and full-length BMP-7 on epithelial-mesenchymal transition (EMT)-related fibrosis. Human peritoneal mesothelial cells (HPMCs) were then treated with TGF-ß1 or TGF-ß1 + PTD-BMP-7. Peritoneal dialysis (PD) catheters were inserted into Sprague-Dawley rats, and these rats were infused intra-peritoneally with saline, peritoneal dialysis fluid (PDF) or PDF + PTD-BMP-7. In vitro, TGF-ß1 treatment significantly increased fibronectin, type I collagen, α-SMA and Snail expression, while reducing E-cadherin expression in HPMCs (P < .001). PTD-BMP-7 treatment ameliorated TGF-ß1-induced fibronectin, type I collagen, α-SMA and Snail expression, and restored E-cadherin expression in HPMCs (P < .001). In vivo, the expressions of EMT-related molecules and the thickness of the sub-mesothelial layer were significantly increased in the peritoneum of rats treated with PDF, and these changes were significantly abrogated by the intra-peritoneal administration of PTD-BMP-7. PTD-BMP-7 treatment significantly inhibited the progression of established PD fibrosis. These findings suggest that PTD-BMP-7, as a prodrug of BMP-7, can be an effective therapeutic agent for peritoneal fibrosis in PD patients.

Sound transmission loss of multi-layered infinite micro-perforated plates.

In this paper, the sound transmission loss (STL) of multi-layered infinite micro-perforated plates (MPPs) is studied. A prediction model for the STL of the multi-layered infinite MPPs is developed, where each MPP may or may not have a perforation, and the number of MPPs is arbitrary. When the frequency of interest is well below the critical frequency of the plate such that the effect of flexural vibration can be neglected compared to that of the inertia term, the mass is replaced by an equivalent complex mass. For numerical examples, single-, double- and triple-layered MPPs are studied. As the perforation ratio increases, the magnitude of the equivalent complex mass decreases rapidly, which in turn results in a decrease of the STL. It is observed that for very small perforation ratios, the mass-spring resonance frequencies in double- and triple-layered MPPs move toward a higher frequency as the perforation ratios increase. In addition, the dips at the resonance frequencies become blunt with increases in the perforation ratios due to the artificial damping induced by micro-perforations. It is also found that at a high frequency, the STL shows dips regardless of the perforation ratios when the wavenumber and air gap depths satisfy certain conditions.

TGF-ß Pathway in Salivary Gland Fibrosis.

Fibrosis is presented in various physiologic and pathologic conditions of the salivary gland. Transforming growth factor beta (TGF-ß) pathway has a pivotal role in the pathogenesis of fibrosis in several organs, including the salivary glands. Among the TGF-ß superfamily members, TGF-ß1 and 2 are pro-fibrotic ligands, whereas TGF-ß3 and some bone morphogenetic proteins (BMPs) are anti-fibrotic ligands. TGF-ß1 is thought to be associated with the pro-fibrotic pathogenesis of sialadenitis, post-radiation salivary gland dysfunction, and Sjögren's syndrome. Potential therapeutic strategies that target multiple levels in the TGF-ß pathway are under preclinical and clinical research for fibrosis. Despite the anti-fibrotic effect of BMPs, their in vivo delivery poses a challenge in terms of adequate clinical efficacy. In this article, we will review the relevance of TGF-ß signaling in salivary gland fibrosis and advances of potential therapeutic options in the field.

Combined treatment with 2'-hydroxycinnamaldehyde and temozolomide suppresses glioblastoma tumorspheres by decreasing stemness and invasiveness.

INTRODUCTION: Glioblastoma (GBM) is the most common and aggressive human primary brain malignancy. The key properties of GBM, stemness and invasiveness, are known to be associated with a highly unfavorable prognosis. Notably, the process of epithelial-mesenchymal transition (EMT) is closely related to the progression of GBM. On the basis of reports that 2'-hydroxycinnamaldehyde (HCA) and its derivative, 2'-benzoyloxycinnamaldehyde (BCA), suppresses EMT in several human cancer cells, we sought to evaluate the therapeutic efficacy of HCA and BCA, alone and in combination with temozolomide (TMZ), on GBM tumorspheres (TSs). METHODS: Two human GBM TSs were treated with HCA, BCA, or TMZ. Therapeutic effects were evaluated by measuring ATP levels, neurosphere formation, 3D-invasion in collagen matrix, and viability. Protein expression profiles after drug treatment were evaluated by western blotting. In vivo anticancer efficacy of drugs was examined in a mouse orthotopic xenograft model. RESULTS: Combined treatment of GBM TSs with HCA or BCA and TMZ significantly reduced cell viability, stemness, and invasiveness. Expression levels of stemness-, invasiveness-, and mesenchymal transition-associated markers, Zeb1, N-cadherin, and ß-catenin, were also substantially decreased by the combined treatment. The combined treatment also reduced tumor growth in a mouse orthotopic xenograft model. CONCLUSION: Our findings suggest that HCA and BCA, combined with TMZ, are potential therapeutic agents in the treatment of GBM.

Multiple Oral Deep Penetrating Nevi Extending to the Masseter and Buccal Fat Pad.

The deep penetrating nevus (DPN) is a rare benign melanocytic tumor often clinically and histopathologically mistaken for malignant melanoma (MM) and other nevus types. This report describes an extremely rare case of multiple lesions of a large DPN in the oral cavity with extensive infiltration to the minor salivary gland, buccal fat pad, buccinators, and masseter muscles, yet with preservation of the normal anatomic architecture. After receiving a diagnosis of MM in another hospital, the patient was at risk for receiving a wide excision that included the masticatory muscles, facial nerve, and overlying skin. Histopathologically, distinct cellular properties were completely masked with heavy pigmentation, thus precluding a proper distinction of benignity versus malignancy. The proliferative capacity of the tumor was analyzed further by immunohistochemistry of bleached tissue sections and tumor behavior was indirectly evaluated by insufficient tumor stromal interaction, with the conclusion that the specimen was benign. Conservative surgery was limited to the oral cavity. Multiple DPNs in the oral cavity merit attention because of the high risk of being mistaken for MM, which would require a wider surgical excision of the head and neck region.

A Case of Pentastomiasis at the Left Maxilla Bone in a Patient with Thyroid Cancer.

Pentastomiasis, a zoonotic parasite infection, is typically found in the respiratory tract and viscera of the host, including humans. Here, we report for the first time an extremely rare case of intraosseous pentastomiasis in the human maxilla suffering from medication related osteonecrosis of the jaw (MRONJ). A 55-year-old male had continuously visited the hospital for MRONJ which had primarily developed after bisphosphonate and anti-neoplastic administration for previous bone metastasis of medullary thyroid cancer. Pain, bone exposure, and pus discharge in the right mandible and left maxilla were seen. Osteolysis with maxillary cortical bone perforation at the left buccal vestibule, palate, nasal cavity, and maxillary sinus was observed by radiologic images. A biopsy was done at the left maxilla and through pathological evaluation, a parasite with features of pentastome was revealed within the necrotic bone tissue. Further history taking and laboratory evaluation was done. The parasite was suspected to be infected through maxillary open wounds caused by MRONJ. Awareness of intraosseous pentastomiasis should be emphasized not to be missed behind the MRONJ. Proper evaluation and interpretation for past medical history may lead to correct differential diagnosis and therapeutic intervention for parasite infections.

Sound transmission loss of double plates with an air cavity between them in a rigid duct.

In this paper, the sound transmission loss (STL) of thin double plates with an air cavity between them in a rigid duct is considered using an analytical approach. The vibration motion of the plate and sound pressure field are expanded in terms of an infinite series of the modal functions. Under the plane wave condition, a low frequency solution is derived by including the first few symmetric modes. It is determined that the peak frequencies of the double plates coincide with those of each single plate. When the two plates are identical, the STL becomes zero at the natural frequencies of the single plate. However, when the two plates are not identical, the STL is always greater than zero. The location and amplitude of the dips are investigated using an approximate solution when the cavity depth is very small. It is observed that dividing the single plate into two plates with an air cavity in between degrades the STL in the low frequency range, while the equivalent surface mass density is preserved. However, when the cavity depth is not small, the STL of the single plate can be smaller than that of the double plates.

Teriparatide therapy for bisphosphonate-related osteonecrosis of the jaw associated with dental implants.

This report describes a case of teriparatide (TPTD) therapy for bisphosphonate (BP)-related osteonecrosis of the jaw induced after implant placement. A 75-year-old woman taking oral BP was referred with uncontrolled osteonecrosis of the mandible related to the implant placement. With conservative treatment, BP was suspended and daily subcutaneous injections of 20 µm/d TPTD were started. After 4 months of the therapy, fixture removal and sequestrectomy were performed. Histological analysis revealed necrotic lamellar bone and empty osteocytic lacunae. In contrast, multiple irregular reversal lines of the lamellar bone and active osteoblasts were noted adjacent to the lesion. There was a significant increase in serum C-terminal telopeptide cross-link of type 1 collagen and serum osteocalcin after commencement of the therapy. After 7 months off therapy, the serum levels of the 2 markers remained at a high level compared with the baseline.

Snail1 is stabilized by O-GlcNAc modification in hyperglycaemic condition.

Protein O-phosphorylation often occurs reciprocally with O-GlcNAc modification and represents a regulatory principle for proteins. O-phosphorylation of serine by glycogen synthase kinase-3ß on Snail1, a transcriptional repressor of E-cadherin and a key regulator of the epithelial-mesenchymal transition (EMT) programme, results in its proteasomal degradation. We show that by suppressing O-phosphorylation-mediated degradation, O-GlcNAc at serine112 stabilizes Snail1 and thus increases its repressor function, which in turn attenuates E-cadherin mRNA expression. Hyperglycaemic condition enhances O-GlcNAc modification and initiates EMT by transcriptional suppression of E-cadherin through Snail1. Thus, dynamic reciprocal O-phosphorylation and O-GlcNAc modification of Snail1 constitute a molecular link between cellular glucose metabolism and the control of EMT.

How much colonic redundancy could be obtained by splenic flexure mobilization in laparoscopic anterior or low anterior resection?

BACKGROUND AND OBJECTIVES: Splenic flexure mobilization (SFM) is performed to ensure a tension free anastomosis with an adequate resection margin in laparoscopic anterior resection (AR) or low anterior resection (LAR). This retrospective study was performed to determine the amount of colonic redundancy that can be expected by SFM. METHODS: Retrospective review of medical record for a total of 203 patients who underwent SFM during laparoscopic AR or LAR for the treatment of sigmoid colon or rectal cancer was performed. RESULTS: The obtained redundancy of the colon by SFM was 27.81 ± 7.29 cm from the sacral promontory. The redundancy of the colon by SFM with high ligation of the inferior mesenteric vein (IMV) (29.54 ± 7.17 cm from the sacral promontory) was greater than that with low ligation of the IMV (24.94 ± 6.07 cm from the sacral promontory, P < 0.0001). It took about 9.82% of the total operation time to perform SFM. There was no intraoperative complication during SFM. CONCLUSIONS: SFM during laparoscopic AR or LAR is a safe and feasible option. Based on the result of this study, one can gain about 27.81 cm redundancy of the colon by SFM.

2-Hydroxycinnamaldehyde inhibits the epithelial-mesenchymal transition in breast cancer cells.

Since epithelial-mesenchymal transition (EMT) plays a critical role in cancer progression and in maintaining cancer stem cell properties, EMT is emerging as a therapeutic target for inhibiting the metastatic progression of cancer cells. 2'-Hydroxycinnamaldehyde (HCA) and its derivative, 2'-benzoyloxycinnamaldehyde, have recently been suggested as promising therapeutic candidates for cancer treatment. The purpose of this study is to investigate the anti-metastatic effect of HCA on breast cancer and the molecular mechanisms by which HCA regulates the transcriptional program during EMT. HCA induces epithelial reversion at nanomolar concentrations by suppressing Snail via the nuclear translocalization of GSK-3ß, which results in the transcriptional upregulation of E-cadherin. HCA also activates the transcription factor KLF17, which suppresses Id-1, indicating that HCA inhibits EMT by multiple transcriptional programs. Further, HCA treatment significantly inhibits lung metastasis in a mouse orthotopic breast cancer model. This study demonstrates the anti-metastatic effect of the non-toxic natural compound HCA through attenuation of EMT in a breast cancer model.

A Wnt-Axin2-GSK3beta cascade regulates Snail1 activity in breast cancer cells.

Accumulating evidence indicates that hyperactive Wnt signalling occurs in association with the development and progression of human breast cancer. As a consequence of engaging the canonical Wnt pathway, a beta-catenin-T-cell factor (TCF) transcriptional complex is generated, which has been postulated to trigger the epithelial-mesenchymal transition (EMT) that characterizes the tissue-invasive phenotype. However, the molecular mechanisms by which the beta-catenin-TCF complex induces EMT-like programmes remain undefined. Here, we demonstrate that canonical Wnt signalling engages tumour cell dedifferentiation and tissue-invasive activity through an Axin2-dependent pathway that stabilizes the Snail1 zinc-transcription factor, a key regulator of normal and neoplastic EMT programmes. Axin2 regulates EMT by acting as a nucleocytoplasmic chaperone for GSK3beta, the dominant kinase responsible for controlling Snail1 protein turnover and activity. As dysregulated Wnt signalling marks a diverse array of cancerous tissue types, the identification of a beta-catenin-TCF-regulated Axin2-GSK3beta-Snail1 axis provides new mechanistic insights into cancer-associated EMT programmes.

Depression in non-Korean women residing in South Korea following marriage to Korean men.

PURPOSE: The purpose of the study was to examine the roles of acculturative stress, life satisfaction, and language literacy in depression in non-Korean women residing in South Korea following marriage to Korean men. METHODS: A cross-sectional study was performed, using an anonymous, self-reporting questionnaire. A total of 173 women were selected using a proportional stratified random sampling method. The relation between acculturation, depression, language literacy, life satisfaction and socio-demographic variables and the predictors of depression among participants were analyzed. The analysis included descriptive statistics and hierarchical multiple regression. RESULTS: Of the participants, 9.2% had depression, which was almost twice the rate of depression found in the general Korean population. In hierarchical multiple regression analysis, acculturative stress (beta=-.325, P<.001) and life satisfaction (beta=-.282, P=.003) were significantly associated with the level of depression. This final model was statistically significant and life satisfaction, acculturative stress, language literacy accounted for 31.0% (adjusted R(2)) of the variance in the depression score (P<.001). CONCLUSIONS: Elevated acculturative stress and less life satisfaction were significantly associated with a higher level of depression in migrant wives in Korea. Implications for practice and research are discussed.