BACKGROUND: Previous randomized controlled trials (RCTs) have reported inconsistent findings regarding the association between vitamin C supplementation and the risk of cancer. METHODS: We performed a meta-analysis of RCTs to investigate the efficacy of vitamin C supplements for prevention of cancer. We searched the PubMed, EMBASE, and Cochrane Library databases in November 2014 using common keywords related to vitamin C supplements and cancer. RESULTS: Among 785 articles, a total of seven trials were identified, which included 62,619 participants; 31,326 and 31,293 were randomized to vitamin C supplementation and control or placebo groups, respectively, which were included in the final analysis. A fixed-effects meta-analysis of all seven RCTs revealed no significant association between vitamin C supplementation and cancer (relative risk, 1.00; 95% confidence intervals, 0.95-1.05). Similarly, subgroup meta-analysis by dose of vitamin C administered singly or in combination with other supplements, follow-up period, methodological quality, cancer mortality, gender, smoking status, country, and type of cancer also showed no efficacy of vitamin C supplementation for cancer prevention. CONCLUSION: This meta-analysis shows that there is no evidence to support the use of vitamin C supplements for prevention of cancer.
Ascorbic Acid* ; Follow-Up Studies ; Mortality ; Smoke ; Smoking ; Vitamins*

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

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

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*

The coagulation profile of patients with end-stage liver disease (ESLD) is different from that of healthy individuals. Because hemostasis is rebalanced in chronic liver disease, prophylactic transfusion of blood products may be not necessary for these patients even if they show severe coagulation dysfunction in conventional coagulation results. A 44-year-old man with hepatocellular carcinoma, cholangiocarcinoma and liver cirrhosis was scheduled for extra-hepatic mass excision under general anesthesia. His preoperative tests showed severe thrombocytopenia 19 × 10⁹/L. The patient underwent extrahepatic mass excision surgery under general anesthesia without transfusion of blood products. The post-operative course was uneventful without requiring any further hemostatic therapy. In this case report, we focus on the concept of rebalanced hemostasis in ESLD, and coagulation management based on rotational thromboelastometry.
Adult ; Anesthesia, General ; Blood Coagulation ; Blood Platelets* ; Carcinoma, Hepatocellular ; Cholangiocarcinoma ; Hemostasis* ; Humans ; Liver Cirrhosis ; Liver Diseases* ; Liver* ; Platelet Count* ; Thrombelastography ; Thrombocytopenia

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.

Hematopoiesis involves a series of lineage differentiation programs initiated in hematopoietic stem cells (HSCs) found in bone marrow (BM). To ensure lifelong hematopoiesis, various molecular mechanisms are needed to maintain the HSC pool. CCCTC-binding factor (CTCF) is a DNA-binding, zinc-finger protein that regulates the expression of its target gene by organizing higher order chromatin structures. Currently, the role of CTCF in controlling HSC homeostasis is unknown. Using a tamoxifen-inducible CTCF conditional knockout mouse system, we aimed to determine whether CTCF regulates the homeostatic maintenance of HSCs. In adult mice, acute systemic CTCF ablation led to severe BM failure and the rapid shrinkage of multiple c-Kit(hi) progenitor populations, including Sca-1⁺ HSCs. Similarly, hematopoietic system-confined CTCF depletion caused an acute loss of HSCs and highly increased mortality. Mixed BM chimeras reconstituted with supporting BM demonstrated that CTCF deficiency-mediated HSC depletion has both cell-extrinsic and cell-intrinsic effects. Although c-Kit(hi) myeloid progenitor cell populations were severely reduced after ablating Ctcf, c-Kit(int) common lymphoid progenitors and their progenies were less affected by the lack of CTCF. Whole-transcriptome microarray and cell cycle analyses indicated that CTCF deficiency results in the enhanced expression of the cell cycle-promoting program, and that CTCF-depleted HSCs express higher levels of reactive oxygen species (ROS). Importantly, in vivo treatment with an antioxidant partially rescued c-Kit(hi) cell populations and their quiescence. Altogether, our results suggest that CTCF is indispensable for maintaining adult HSC pools, likely by regulating ROS-dependent HSC quiescence.
Adult ; Animals ; Bone Marrow ; Cell Cycle ; Chimera ; Chromatin ; Fibrinogen* ; Hematopoiesis ; Hematopoietic Stem Cells* ; Homeostasis ; Humans ; Lymphoid Progenitor Cells ; Mice* ; Mice, Knockout ; Mortality ; Myeloid Progenitor Cells ; Reactive Oxygen Species

Background: CycloZ, a combination of cyclo-His-Pro and zinc, has anti-diabetic activity. However, its exact mode of action remains to be elucidated. Methods: KK-Ay mice, a type 2 diabetes mellitus (T2DM) model, were administered CycloZ either as a preventive intervention, or as a therapy. Glycemic control was evaluated using the oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) levels. Liver and visceral adipose tissues (VATs) were used for histological evaluation, gene expression analysis, and protein expression analysis. Results: CycloZ administration improved glycemic control in KK-Ay mice in both prophylactic and therapeutic studies. Lysine acetylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, liver kinase B1, and nuclear factor-κB p65 was decreased in the liver and VATs in CycloZ-treated mice. In addition, CycloZ treatment improved mitochondrial function, lipid oxidation, and inflammation in the liver and VATs of mice. CycloZ treatment also increased the level of β-nicotinamide adenine dinucleotide (NAD+), which affected the activity of deacetylases, such as sirtuin 1 (Sirt1). Conclusion Our findings suggest that the beneficial effects of CycloZ on diabetes and obesity occur through increased NAD+ synthesis, which modulates Sirt1 deacetylase activity in the liver and VATs. Given that the mode of action of an NAD+ booster or Sirt1 deacetylase activator is different from that of traditional T2DM drugs, CycloZ would be considered a novel therapeutic option for the treatment of T2DM.

PURPOSE: This study aimed to report intraoperative abortion of adult living donor liver transplantation (LDLT). METHODS: From June 1997 to December 2016, 1,179 adult LDLT cases were performed. 15 cases (1.3%) of intraoperative abortions in LDLT were described. RESULTS: Among 15 cases, 5 intraoperative abortions were donor-related, and remaining 10 cases were recipient-related. All donor-related abortions were due to unexpected steatohepatitis. Among remaining 10 recipient-related intraoperative abortions, unexpected extension of hepatocellular carcinoma was related in 5 cases. Two cases of intraoperative abortions were related to bowel inflammation, and 2 cases were associated with severe adhesion related to previous treatment. One recipient with severe pulmonary hypertension was also aborted. CONCLUSION: Complete prevention of aborted LDLT is still not feasible. In this regard, further efforts to minimize intraoperative abortion are required.
Adult* ; Carcinoma, Hepatocellular ; Fatty Liver ; Humans ; Hypertension, Pulmonary ; Inflammation ; Liver Transplantation* ; Liver* ; Living Donors* ; Postoperative Care