Obesity is consistently increasing in prevalence and can trigger insulin resistance and type 2 diabetes. Many lines of evidence have shown that macrophages play a major role in inflammation associated with obesity. This study was conducted to determine metformin, a widely prescribed drug for type 2 diabetes, would regulate inflammation through down-regulation of scavenger receptors in macrophages from obesity-induced type 2 diabetes. RAW 264.7 cells and peritoneal macrophages were stimulated with LPS to induce inflammation, and C57BL/6N mice were fed a high-fat diet to generate obesity-induced type 2 diabetes mice. Metformin reduced the production of NO, PGE2 and pro-inflammatory cytokines (IL-1beta, IL-6 and TNF-alpha) through down-regulation of NF-kappaB translocation in macrophages in a dose-dependent manner. On the other hand, the protein expressions of anti-inflammatory cytokines, IL-4 and IL-10, were enhanced or maintained by metformin. Also, metformin suppressed secretion of TNF-alpha and reduced the protein and mRNA expression of TNF-alpha in obese mice as well as in macrophages. The expression of scavenger receptors, CD36 and SR-A, were attenuated by metformin in macrophages and obese mice. These results suggest that metformin may attenuate inflammatory responses by suppressing the production of TNF-alpha and the expressions of scavenger receptors.
Animals ; Cytokines ; Diet, High-Fat ; Dinoprostone ; Down-Regulation ; Hand ; Inflammation ; Insulin Resistance ; Interleukin-10 ; Interleukin-4 ; Interleukin-6 ; Macrophages ; Macrophages, Peritoneal ; Metformin ; Mice ; Mice, Obese ; NF-kappa B ; Obesity ; Prevalence ; Receptors, Scavenger ; RNA, Messenger ; Tumor Necrosis Factor-alpha

PURPOSE: There is no standard targeted therapy for the treatment of triple-negative breast cancer (TNBC). Therefore, its management heavily depends on adjuvant chemotherapy. Using core needle biopsy, this study evaluated the histological factors of TNBC predicting the response to chemotherapy. METHODS: One hundred forty-three TNBC patients who received single-regimen neoadjuvant chemotherapy (NAC) with the combination of doxorubicin, cyclophosphamide, and docetaxel were enrolled. The core needle biopsy specimens acquired before NAC were used to analyze the clinicopathologic variables and overall performance of the predictive model for therapeutic response. RESULTS: Independent predictors of pathologic complete response after NAC were found to be higher number of tumor infiltrating lymphocytes (p=0.007), absence of clear cytoplasm (p=0.008), low necrosis (p=0.018), and high histologic grade (p=0.039). In the receiver operating characteristics curve analysis, the area under curve for the combination of these four variables was 0.777. CONCLUSION: The present study demonstrated that a predictive model using the above four variables can predict therapeutic response to single-regimen NAC with the combination of doxorubicin, cyclophosphamide, and docetaxel in TNBC. Therefore, adding these morphologic variables to clinical and genomic signatures might enhance the ability to predict the therapeutic response to NAC in TNBC.
Area Under Curve ; Biopsy, Large-Core Needle ; Chemotherapy, Adjuvant ; Cyclophosphamide ; Cytoplasm ; Doxorubicin ; Drug Therapy* ; Humans ; Lymphocytes, Tumor-Infiltrating ; Necrosis ; Neoadjuvant Therapy ; ROC Curve ; Treatment Outcome ; Triple Negative Breast Neoplasms*

Dioscoreae Rhizome (DR) has been used in traditional medicine to treat numerous diseases and is reported to have anti-diabetes and anti-tumor activities. To identify a bioactive traditional medicine with anti-inflammatory activity of a water extract of DR (EDR), we determined the mRNA and protein levels of proinflammatory cytokines in macrophages through RT-PCR and western blot analysis and performed a FACS analysis for measuring surface molecules. EDR dose-dependently decreased the production of NO and pro-inflammatory cytokines such as IL-1beta, IL-6, TNF-alpha, and PGE2, as well as mRNA levels of iNOS, COX-2, and pro-inflammatory cytokines, as determined by western blot and RT-PCR analysis, respectively. The expression of co-stimulatory molecules such as B7-1 and B7-2 was also reduced by EDR. Furthermore, activation of the nuclear transcription factor, NF-kappaB, but not that of IL-4 and IL-10, in macrophages was inhibited by EDR. These results show that EDR decreased pro-inflammatory cytokines via inhibition of NF-kappaB-dependent inflammatory protein level, suggesting that EDR could be a useful immunomodulatory agent for treating immunological diseases.
Blotting, Western ; Cytokines ; Dinoprostone ; Dioscorea ; Immune System Diseases ; Inflammation ; Interleukin-10 ; Interleukin-4 ; Interleukin-6 ; Macrophages ; Medicine, Traditional ; NF-kappa B ; Rhizome ; RNA, Messenger ; Transcription Factors ; Tumor Necrosis Factor-alpha ; Water

OBJECTIVES: To compare the white matter microstructure of dyslexic children with normal children using diffusion tensor imaging. METHODS: Twenty one dyslexic children and 24 normal control children were recruited in the second and third grade of elementary school students. The fractional anisotropy (FA) values of 20 representative white matter tracts were estimated from the diffusion tensor imaging data of each subject using the Johns Hopkins University-white matter tractography atlas to determine the difference in white matter integrity between the dyslexic children and normal children. RESULTS: Compared to the normal control group, the FA values of the left inferior longitudinal fasciculus [F(1,39)=5.908, p<0.05] and temporal part of the right superior longitudinal fasciculus [F(1,39)=7.328, p=0.010] were significantly higher in the dyslexic group and there was no significant difference in the other tracts. CONCLUSION: In dyslexic children, compensatory pathways develop in the left inferior longitudinal fasciculus and in the temporal part of the right superior longitudinal fasciculus.
Anisotropy ; Case-Control Studies ; Child ; Diffusion Tensor Imaging ; Dyslexia ; Humans ; White Matter

Purpose: Korea has implemented an early screening for colorectal cancer since 2004. However, it is not known whether this has translated into improved survival over the years. Methods: We acquired colorectal cancer mortality data from the Cause of Death Statistics in Korea from 2000 to 2020. We characterized the data into year of death, cancer-specific loci, and age group. We analyzed age-standardized mortality rates (ASMR) according to year of death, age group, and primary location to find trends in colorectal cancer mortality over a 20-year period. Results: The crude mortality rate of colorectal cancer increased from 8.78 per 100,000 in 2000 to 17.27 per 100,000 in 2020. The second decade was slower in increments compared to the first decade. ASMR showed a decrease over the second decade after an initial increase in the first decade. The decrease was primarily from the lowering of ASMR for rectosigmoid cancers. Age group analysis showed a lowering of ASMR mainly in the 45–59-year, 60–74-year, and ≥ 75-year age groups; however, 0–29-year and 30–44-year age groups showed generally unchanged ASMR over the total period. Conclusion After a brief incline of age-specific mortality of colorectal cancers during the early 2000s, colorectal cancer mortality has gradually been decreasing in the past decade. This was mainly due to decreased mortalities in rectosigmoid colon cancers especially in the age groups that were the target of early screening.

Metformin is widely used for T2D therapy but its cellular mechanism of action is undefined. Recent studies on the mechanism of metformin in T2D have demonstrated involvement of the immune system. Current immunotherapies focus on the potential of immunomodulatory strategies for the treatment of T2D. In this study, we examined the effects of metformin on the antigen-presenting function of antigen-presenting cells (APCs). Metformin decreased both MHC class I and class II-restricted presentation of OVA and suppressed the expression of both MHC molecules and co-stimulatory factors such as CD54, CD80, and CD86 in DCs, but did not affect the phagocytic activity toward exogenous OVA. The class II-restricted OVA presentation-regulating activity of metformin was also confirmed using mice that had been injected with metformin followed by soluble OVA. These results provide an understanding of the mechanisms of the T cell response-regulating activity of metformin through the inhibition of MHC-restricted antigen presentation in relation to its actions on APCs.
Animals ; Antigen Presentation* ; Antigen-Presenting Cells ; Immune System ; Immunotherapy ; Metformin* ; Mice ; Ovum

Objective: Bipolar disorder displays a spectrum of manifestations, including manic, hypomanic, depressive, mixed, psychotic, and atypical episodes, contributing to its chronic nature and association with heightened suicide risk. Creating effective pharmacotherapy guidelines is crucial for managing bipolar disorder and reducing its prevalence. Treatment algorithms grounded in science have improved symptom management, but variations in recommended medications arise from research differences, healthcare policies, and cultural nuances globally. Methods: This study compares Korea’s bipolar disorder treatment algorithm with guidelines from the UK, Australia, and an international association. The aim is to uncover disparities in key recommended medications and their underlying factors. Differences in CYP450 genotypes affecting drug metabolism contribute to distinct recommended medications. Variances also stem from diverse guideline development approaches—expert consensus versus metaanalysis results—forming the primary differences between Korea and other countries. Results: Discrepancies remain in international guidelines relying on meta-analyses due to timing and utilized studies. Drug approval speeds further impact medication selection. However, limited high-quality research results are the main cause of guideline variations, hampering consistent treatment conclusions. Conclusion Korea’s unique Delphi-based treatment algorithm stands out. To improve evidence-based recommendations, large-scale studies assessing bipolar disorder treatments for the Korean population are necessary. This foundation will ensure future recommendations are rooted in scientific evidence.