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.

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.

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

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

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

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*