Ovarian cancer remains one of the most lethal gynecologic malignancies, with limited responsiveness to standard chemotherapy and poor long-term prognosis. Tumor-associated macrophages, particularly M2-polarized populations, play a crucial role in immune suppression and tumor progression. Human induced pluripotent stem cells (hiPSCs) can differentiate into functional immune cells, providing an unlimited and patient-specific source for cell-based immunotherapy.In this study, we investigated the therapeutic potential of hiPSC-derived macrophages (hiMACs), specifically M1-polarized hiMACs, against ovarian cancer. In a co-culture system, M1-hiMACs significantly reduced the viability of ovarian cancer cells, inducing apoptosis and necrosis, whereas M0 macrophages showed minimal effects. In vivo, intravenous administration of M1-hiMACs into nude mice bearing ovarian cancer cells resulted in a dose-dependent reduction in tumor volume. Furthermore, combination therapy with paclitaxel and M1-hiMACs led to greater tumor regression and enhanced histological necrosis compared to either treatment alone. These findings demonstrate the potent anti-tumor effects of M1-hiMACs and highlight their potential for cellular immunotherapy for ovarian cancer, particularly in combination with chemotherapy.

This study was performed to assess the antiapoptotic effect of canine platelet-rich plasma (PRP) treated on the canine adipose-derived mesenchymal stem cells (cMSCs) under cold ischemic conditions. The effect of preventing apoptosis of cMSCs was evaluated in the apoptotic condition induced by cold ischemic injury in vitro. To determine the progression of apoptosis, the changes in cell nucleus were observed using 4',6-diamidino-2-phenylindole (DAPI) fluorescence staining. In addition, we examined the mitochondrial membrane potential (MMP) and caspase-3 activity. When the cold hypoxic injury was applied to cMSCs, the apoptotic change was observed by DAPI staining, mitochondrial staining for MMP, and caspase-3 assay. PRP significantly decreased the number of apoptotic cells. Nuclear shrinkage and fragmentation of apoptotic cells in control groups were observed by DAPI staining. The MMP was recovered by the treatment of PRP. In addition, when the luminescence intensity was measured for caspase-3 activity, the value was significantly higher in the PRP treated groups than the control groups. The results of this study showed that the PRP may have a beneficial effect on apoptosis induced by cold ischemic injury.

BACKGROUND/OBJECTIVES: The prevalence of hypertension is increasing, and noodles have a high sodium content, so noodle consumption might be associated with a higher prevalence of hypertension. This study aimed to analyze the association between total and types of noodle intake and the risk of hypertension among Korean adults. Subjects aged 40–69 years were selected for this study. SUBJECTS/METHODS: This study included 56,580 participants (18,246 men and 38,334 women) aged 40–69 years old from the Health Examinees study. Noodle and nutrient intakes were assessed using the food frequency questionnaire. Hypertension was diagnosed as systolic blood pressure ≥ 140 mmHg and/or diastolic blood pressure ≥ 90 mmHg or antihypertensive medication use. Cox proportional hazard models were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for hypertension. RESULTS: Higher noodle consumption was associated with increased hypertension among men (HR, 1.273; 95% CI, 1.166–1.390) and women (HR, 1.116; 95% CI, 1.038–1.199). CONCLUSION We recommended reducing noodle intake and consuming vegetables and fruits to increase potassium intake, which can prevent vascular diseases.

Complex regional pain syndrome (CRPS) is a chronic neuropathic pain disorder. Pain catastrophizing, characterized by magnification, rumination, and helplessness, increases perceived pain intensity and mental distress in CRPS patients. As functional connectivity patterns in CRPS remain largely unknown, we aimed to investigate functional connectivity alterations in CRPS patients and their association with pain catastrophizing using a whole-brain analysis approach. Twenty-one patients with CRPS and 49 healthy controls were included in the study for clinical assessment and resting-state functional magnetic resonance imaging. Between-group differences in whole-brain functional connectivity were examined through a Network-based Statistics analysis. Associations between altered functional connectivity and the extent of pain catastrophizing were also assessed in CRPS patients. Relative to healthy controls, CRPS patients showed higher levels of functional connectivity in the bilateral somatosensory subnetworks (components 1~2), but lower functional connectivity within the prefronto-posterior cingulate (component 3), prefrontal (component 4), prefronto-parietal (component 5), and thalamo-anterior cingulate (component 6) subnetworks (p<0.05, family-wise error corrected). Higher levels of functional connectivity in components 1~2 (β=0.45, p=0.04) and lower levels of functional connectivity in components 3~6 (β=-0.49, p=0.047) were significantly correlated with higher levels of pain catastrophizing in CRPS patients. Higher functional connectivity in the somatosensory subnetworks implicating exaggerated pain perception and lower functional connectivity in the prefronto-parieto-cingulo-thalamic subnetworks indicating impaired cognitive-affective pain processing may underlie pain catastrophizing in CRPS.

Objective: We aimed to evaluate the ostium of right coronary artery of anomalous origin from the left coronary sinus (AORL) with an interarterial course throughout the cardiac cycle on CT and analyze the clinical significance of the ostial findings. Materials and Methods: From January 2011 to December 2015, 68 patients (41 male, 57.3 ± 12.1 years) with AORL with an interarterial course and retrospective cardiac CT data were included. AORL was classified as high or low ostial location based on the pulmonary annulus in the diastolic and systolic phases on cardiac CT. In addition, the height, width, height/width ratio, area, and angle of the ostium were measured in both cardiac phases. After cardiac CT, patients were followed until December 31, 2020 for major adverse cardiac events (MACE). Clinical and CT characteristics associated with MACE were explored using Cox regression analysis. Results: During a median follow-up period of 2071 days (interquartile range, 1180.5–2747.3 days), 13 patients experienced MACE (19.1%, 13/68). Seven (10.3%, 7/68) had the ostial location change from high in the diastolic phase to low in the systolic phase. In the univariable analysis, younger age (hazard ratio [HR] = 0.918, p < 0.001), high ostial location (HR = 4.008, p = 0.036), larger height/width ratio (HR = 5.621, p = 0.049), and smaller ostial angle (HR = 0.846, p = 0.048) in the systolic phase were significant predictors of MACE. In multivariable cox regression analysis, younger age (adjusted HR = 0.917, p = 0.002) and high ostial location in the systolic phase (adjusted HR = 4.345, p = 0.026) were independent predictors of MACE. Conclusion The ostial location of AORL with an interarterial course can change during the cardiac cycle, and high ostial location in the systolic phase was an independent predictor of MACE.

The COVID-19 pandemic has had a major impact worldwide, making it difficult to transplant unrelated hematopoietic stem cells. On the other hand, cord blood transplantations in Korea increased during the pandemic. In 2021, the release of 110 cord blood units and 83 cord blood transplantations were performed. Cord blood transplants have increased by 35% compared to the pre-pandemic period (average of 58 cases over four years vs. 78 cases over two years). This phenomenon is not only occurring in Korea. In France, cord blood transplantation in 2020 increased by 19% compared to the previous year. The cord blood is the blood in the umbilical cord and placenta that would be discarded during childbirth but can be used as a useful source of hematopoietic stem cells in the COVID-19 pandemic. In addition, it is essential to collect and store high-quality cord blood continuously because of the high likelihood of developing various therapeutic agents using cord blood.

Objective: Subjective cognitive impairment (SCI) is associated with future cognitive decline. This study aimed to compare cortical thickness and local gyrification index (LGI) between individuals with SCI and normal control (NC) subjects. Methods: Forty-seven participants (27 SCI and 20 NC) were recruited. All participants underwent brain magnetic resonance imaging scanning and were clinically assessed using the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) battery of tests. We compared cortical thickness and LGI between the two groups and analyzed correlations between cortical thickness/LGI and scores on CERAD protocol subtests in the SCI group for region of interests with significant between-group differences. Results: Cortical thickness reduction in the left entorhinal, superior temporal, insular, rostral middle frontal, precentral, superior frontal, and supramarginal regions, and right supramarginal, precentral, insular, postcentral, and posterior cingulate regions was observed in the SCI compared to the NC group. Cortical thickness in these regions correlated with scores of constructional praxis, word list memory, word list recall, constructional recall, trail making test A, and verbal fluency under the CERAD protocol. Significantly decreased gyrification was observed in the left lingual gyrus of the SCI group. In addition, gyrification of this region was positively associated with scores of constructional praxis. Conclusion Our results may provide an additional reference to the notion that SCI may be associated with future cognitive impairment. This study may help clinicians to assess individuals with SCI who may progress to mild cognitive impairment and Alzheimer’s dementia.

Vascular endothelial growth factor (VEGF) plays a pivotal role in pathologic ocular neovascularization and vascular leakage via activation of VEGF receptor 2 (VEGFR2). This study was undertaken to evaluate the therapeutic mechanisms and effects of the tetrapeptide Arg-Leu-Tyr-Glu (RLYE), a VEGFR2 inhibitor, in the development of vascular permeability and choroidal neovascularization (CNV). In cultured human retinal microvascular endothelial cells (HRMECs), treatment with RLYE blocked VEGF-A-induced phosphorylation of VEGFR2, Akt, ERK, and endothelial nitric oxide synthase (eNOS), leading to suppression of VEGF-A-mediated hyper-production of NO. Treatment with RLYE also inhibited VEGF-A-stimulated angiogenic processes (migration, proliferation, and tube formation) and the hyperpermeability of HRMECs, in addition to attenuating VEGF-A-induced angiogenesis and vascular permeability in mice. The anti-vascular permeability activity of RLYE was correlated with enhanced stability and positioning of the junction proteins VE-cadherin, β-catenin, claudin-5, and ZO-1, critical components of the cortical actin ring structure and retinal endothelial barrier, at the boundary between HRMECs stimulated with VEGF-A. Furthermore, intravitreally injected RLYE bound to retinal microvascular endothelium and inhibited laser-induced CNV in mice. These findings suggest that RLYE has potential as a therapeutic drug for the treatment of CNV by preventing VEGFR2-mediated vascular leakage and angiogenesis.
Actins ; Animals ; Capillary Permeability ; Choroid ; Choroidal Neovascularization ; Claudin-5 ; Endothelial Cells ; Endothelium ; Humans ; Macular Degeneration ; Mice ; Nitric Oxide Synthase Type III ; Permeability ; Phosphorylation ; Receptors, Vascular Endothelial Growth Factor ; Retinaldehyde ; Vascular Endothelial Growth Factor A

The global obesity epidemic and associated metabolic diseases require alternative biological targets for new therapeutic strategies. In this study, we show that a phytochemical sulfuretin suppressed adipocyte differentiation of preadipocytes and administration of sulfuretin to high fat diet-fed obese mice prevented obesity and increased insulin sensitivity. These effects were associated with a suppressed expression of inflammatory markers, induced expression of adiponectin, and increased levels of phosphorylated ERK and AKT. To elucidate the molecular mechanism of sulfuretin in adipocytes, we performed microarray analysis and identified activating transcription factor 3 (Atf3) as a sulfuretin-responsive gene. Sulfuretin elevated Atf3 mRNA and protein levels in white adipose tissue and adipocytes. Consistently, deficiency of Atf3 promoted lipid accumulation and the expression of adipocyte markers. Sulfuretin’s but not resveratrol’s anti-adipogenic effects were diminished in Atf3 deficient cells, indicating that Atf3 is an essential factor in the effects of sulfuretin. These results highlight the usefulness of sulfuretin as a new anti-obesity intervention for the prevention of obesity and its associated metabolic diseases.
Activating Transcription Factor 3 ; Adipocytes ; Adiponectin ; Adipose Tissue, White ; Animals ; Diet* ; Insulin Resistance ; Metabolic Diseases* ; Mice ; Mice, Obese* ; Microarray Analysis ; Obesity* ; RNA, Messenger

OBJECTIVE: To analyze the relationship between seizure threshold (ST) and psychotropic drugs in patients treated with ECT. METHODS: We examined clinical data from 43 patients. ST was titrated at each treatment session. We examined associations between ST and psychotropic drugs using multivariate correlation analyses. Data are presented as initial ST, the difference in ST between the first and 10th sessions (ΔST(10th)), and the mean difference in ST between the first and last sessions (mean ΔST(last)). RESULTS: Multivariate regression analyses showed associations between initial ST and the total chlorpromazine-equivalent dose of antipsychotics (β=0.363, p<0.05). The total fluoxetine-equivalent dose of antidepressants was associated with ΔST(10th) (β=0.486, p<0.01) and mean ΔST(last) (β=0.472, p<0.01). CONCLUSION: Our study elucidated possible effects of psychotropic drugs on ST shifts. Larger doses of antipsychotics were associated with higher initial ST, whereas higher doses of antidepressants were associated with stronger shifts in ST.
Antidepressive Agents ; Antipsychotic Agents ; Electroconvulsive Therapy* ; Humans ; Psychotropic Drugs* ; Seizures*