BACKGROUND/OBJECTIVES: Obesity is a complex metabolic disorder characterized by excessive adipose tissue accumulation, dysregulated lipid metabolism, and insulin resistance, leading to an increased risk of metabolic disease. While Withania somnifera (AS) and Chrysanthemum zawadskii Herbich var. latilobum (Maxim.) Kitamura (C) have traditionally been used for their metabolic regulatory properties, their combined effects on adipogenesis, lipogenesis, lipolysis, and insulin signaling remain unexplored. Therefore, this study aimed to evaluate the anti-obesity effects of AS, C, and their optimal combination (ASC) in 3T3-L1 adipocytes by investigating their impact on lipid metabolism and glucose homeostasis.MATERIALS/METHODS: Following adipogenic differentiation, 3T3-L1 adipocytes were treated with AS, C, and ASC at different concentrations. RESULTS: AS, C, and ASC significantly inhibited adipogenesis by downregulating cyclic adenosine monophosphate (cAMP) response element-binding protein, peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding proteins alpha and beta phosphorylation, thereby reducing lipid accumulation in adipocytes. They also suppressed lipogenesis by downregulating the expression of dephosphorylated acetyl-CoA carboxylase, fatty acid synthase, and lipoprotein lipase. In contrast, they markedly enhanced lipolysis, as evidenced by increased hormone-sensitive lipase and protein kinase A expression, along with elevated glycerol release and cAMP levels. Furthermore, AS, C, and ASC activated energy metabolism pathways, as indicated by the upregulation of AMP-activated protein kinase, uncoupling protein 1, and carnitine palmitoyltransferase 1A, suggesting a transition toward enhanced mitochondrial fatty acid oxidation. Notably, AS, C, and ASC significantly improved insulin signaling by restoring insulin receptor substrate 1, phosphoinositide 3-kinase, and Akt phosphorylation, while upregulating glucose transporter type 4 expression, indicating enhanced glucose uptake. Among all treatments, ASC showed relatively greater efficacy compared to AS or C alone, suggesting a potential additive effect. CONCLUSION These findings demonstrate that ASC effectively modulates multiple metabolic pathways in adipocytes, including adipogenesis, lipogenesis, lipolysis, energy metabolism, and insulin signaling, to exert its anti-obesity effects.

Purpose: According to the guidelines of the Japanese Gastric Cancer Association, endoscopic submucosal dissection (ESD) is safe for gastric cancer (GC) patients with absolute indications because the possibility of lymph node metastasis (LNM) is 0%. The aim of this study was to reveal the exact proportion of Korean GC patients with LNM whose pathological examination revealed indications for ESD. Methods: Data were extracted from the ‘2019 Korean Nationwide Retrospective Database’ managed by the Korean Gastric Cancer Association. Among the 14,076 patients, 4,220 patients with stage T1a cancer after radical gastrectomy were enrolled. Pathological examination was performed to ascertain the tumor diameter, depth of invasion, tumor differentiation, presence of lymphovascular/perineural invasion, and presence of ulceration. Results: The proportion of patients with LNM and absolute indications was 2.4% (49 of 2,012). The 95% confidence interval for the proportion of patients with LNM was greater than 1.0% across all subgroups in terms of absolute indications.According to the multivariate regression model, the risk factors for LNM were lymphovascular invasion (odds ratio [OR], 7.56), perineural invasion (OR, 3.02), a tumor size >2 cm (OR, 2.37), undifferentiated tumors (OR, 2.30), and ulceration (OR, 1.66). Conclusion Compared with Japanese studies, this study revealed a relatively high proportion of Korean GC patients with LNM and absolute indications for ESD. The Japanese guidelines for ESD could be applied to Korean GC patients if done carefully.

BACKGROUND/OBJECTIVES: UV radiation is a major factor contributing to DNA damage in skin cells, including stem cells and mesenchymal stem cells, leading to the depletion of these crucial cells. This study examined whether a mixture of Indian gooseberry and barley sprout (IB) could inhibit UVB irradiation and 3-isobutyl-1-methylxanthine (IBMX)-induced photoaging and oxidative stress in the skin using HaCaT, Hs27, and B16F10 cells.MATERIALS/METHODS: The moisturizing-related factors, the collagen synthesis-related c-Jun N-terminal kinase (JNK)/c-Fos/c-Jun/matrix metalloproteinases (MMPs) pathway, and the melanogenesis-related cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA)/cAMP-responsive binding protein (CREB)/melanocyte inducing transcription factor (MITF)/tyrosinase-related protein (TRP)/tyrosinase activation pathways were analyzed in vitro by an enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and Western blot analysis. RESULTS: The IB complex increased the hyaluronic acid and sphingomyelin levels and the collagenase inhibitory activity, enhanced hydration-related factors, including collagen, hyaluronic acid synthase (HAS), elastin, long chain base subunit 1 (LCB1) (serine palmitoyltransferase; SPT), and delta 4-desaturase sphingolipid 1 (DEGS1), modulated the inflammatory cytokines levels, antioxidant enzyme activities and the NF-κB/MMPs/cyclooxygenase-2 (COX-2) pathway in UVB-irradiated HaCaT cells, and inhibited wrinkle formation by down-regulation of the JNK/c-Fos/c-Jun/MMP pathway and up-regulation of the transforming growth factor-β receptor I (TGFβR1)/small mothers against decapentaplegic homolog (Smad3)/procollagen type I pathway in UVB-irradiated Hs27 cells. Moreover, the IB complex prevented melanin production by down-regulating the PKA/CREB/MITF/TRP-1/TRP-2 pathway in IBMX-induced B16F10 cells. CONCLUSION These findings suggest that the IB complex has the potential to serve as a safeguard, shielding the skin from UVB radiation-induced photo-damage.

Background: This study examined the relationship of infant feeding with anthropometric indices of children during their first six years of life relative to the Korean National Growth Charts (KNGC) and the World Health Organization Child Growth Standards (WHO-CGS). Methods: The study population consisted of 547,669 Korean infants and children who were 6 months-old to 6 years-old (born in 2008–2009) and participated in the National Health Screening Program for Infants and Children. Data on height, weight, and type of feeding during the first 6 months (exclusively breastfed [BF] vs. mixed- or formula-fed [FF]) were analyzed. Results: BF boys and girls were significantly shorter and lighter than FF counterparts from the age of 6 months to 4 years, but these differences were not significant after the age of 4 years. BF boys and girls only had significantly lower body mass index at the age of 2 years. Under the age of 2 years 6 months, and especially under the age of 1 year, BF boys and girls were significantly taller and heavier than the 50th percentile values of the 50th percentile value of the WHO-CGS. Conclusion In this study using large-scaled national data, Korean breastfed children are shorter and lighter by 3 years 6 months–4 years 6 months, but afterward, there is no significant difference from those who had mixed- or formula-feeding. Substantial disparities in the anthropometric indices of Korean infants under the age of 1 compared to KNCG and WHO-CGS were found, regardless of their infantile feeding types. Our results emphasize the importance of constructing a nationwide reference chart based on actual measurements of BF Korean infants.

Angiomyolipoma (AML) is a rare benign mesenchymal tumor in the liver, which is composed of blood vessels, smooth muscle, and adipose cells. The proportion of each component varies, making a diagnosis difficult. This paper reports a case of AML in the liver without adipose tissue, mimicking a hepatocellular carcinoma (HCC), which was diagnosed by a surgical tissue biopsy. A 65-year-old woman was admitted for an evaluation of a hepatic mass that had been detected by ultrasonography. The serologic markers of viral hepatitis B and C were negative. The liver function tests and alpha fetoprotein level were within the normal limits. Magnetic resonance imaging revealed a 1.9 cm sized mass in segment 6 of the liver with early arterial enhancement and washout on the delayed phase accompanied by a rim-like enhancement, which is similar to the imaging findings of HCC. A frozen section examination during surgery indicated a hepatocellular neoplasm and suggested the possibility of HCC. On the other hand, the final pathologic diagnosis was epithelioid myoid type of AML with no adipose tissue component. The tumor cells were positive for human melanocyte B-45 and negative for cytokeratin and hepatocyte paraffin 1. This paper reports a very rare case of AML without adipose tissue in the liver mimicking HCC that was diagnosed by a surgical tissue biopsy.
Adipose Tissue ; Aged ; alpha-Fetoproteins ; Angiomyolipoma ; Biopsy ; Blood Vessels ; Carcinoma, Hepatocellular ; Diagnosis ; Female ; Frozen Sections ; Hand ; Hepatitis B ; Hepatocytes ; Humans ; Keratins ; Liver Function Tests ; Liver ; Magnetic Resonance Imaging ; Melanocytes ; Muscle, Smooth ; Paraffin ; Ultrasonography

To evaluate the carcinogenicity of p27 knockout (KO) mice with RNA-guided endonuclease (RGENs)-mediated p27 mutant exon I gene (IΔ), alterations in the carcinogenic phenotypes including tumor spectrum, tumor suppressor proteins, apoptotic proteins and cell cycle regulators were observed in p27 (IΔ) KO mice after treatment with 7,12-Dimethylbenz[a]anthracene (DMBA) and 12-O-tetradecanoylphorbol-13-acetate (TPA)(DT) for 5 months. The target region (544~571 nt) in exon I of the p27 gene was successfully disrupted in p27 (IΔ) KO mice using the RGEN-induced non-homologous end joining (NHEJ) technique. After DT exposure for 5 months, a few solid tumors (identified as squamous cell carcinoma) developed on the surface of back skin of DT-treated p27 (IΔ) KO mice. Also, squamous cell hyperplasia with chronic inflammation was detected in the skin dermis of DT-treated p27 (IΔ) KO mice, while the Vehicle+p27 (IΔ) KO mice and WT mice maintained their normal histological skin structure. A significant increase was observed in the expression levels of tumor suppressor protein (p53), apoptotic proteins (Bax, Bcl-2 and Caspase-3) and cell-cycle regulator proteins (Cyclin D1, CDK2 and CDK4) in the skin of DT-treated p27 (IΔ) KO mice, although their enhancement ratio was varied. Taken together, the results of the present study suggest that squamous cell carcinoma and hyperplasia of skin tissue can be successfully developed in new p27 (IΔ) KO mice produced by RGEN-induced NHEJ technique following DT exposure for 5 months.
9,10-Dimethyl-1,2-benzanthracene* ; Animals ; Carcinogenesis ; Carcinoma, Squamous Cell* ; Cell Cycle ; Dermis ; Epithelial Cells* ; Exons ; Hyperplasia* ; Inflammation ; Mice* ; Phenotype ; Skin ; Tumor Suppressor Proteins

Regulation of gastrointestinal hormones have been reported in animal models for constipation undergoing laxative therapy when administered herbal products. We undertook to investigate whether the laxative activity of gallotannin-enriched extracts isolated from Galla Rhois (GEGR) affects the regulation of gastrointestinal hormones, by examining the concentration of four hormones and the activation of their receptors in the loperamide (Lop)-induced constipation model. Stool parameters, including number, weight and water content, were significantly recovered in the Lop+GEGR treated group, relative to the Lop+vehicle treated group; however, food intake and water consumption were maintained at a constant level. Also, a similar recovery was detected for thickness of mucosa, muscle and flat luminal surface in the Lop+GEGR treated group. Furthermore, concentration of the four gastrointestinal hormones evaluated, namely, cholecystokinin (CCK), gastrin (GAS), somatostatin (SS) and motilin (MTL), were lower in the Lop+vehicle treated group than the No treated group, but were remarkably enhanced in the Lop+GEGR treated group. Moreover, the downstream signaling pathway of MTL and SS receptors were recovered after GEGR administration. Results of the present study therefore indicate that the laxative effects of GEGR treatment may be tightly related with the regulation of gastrointestinal hormones in the Lop-induced constipation model.
Animals ; Cholecystokinin ; Constipation* ; Drinking ; Eating ; Gastrins ; Gastrointestinal Hormones* ; Loperamide ; Models, Animal ; Motilin ; Mucous Membrane ; Phenobarbital ; Rats* ; Somatostatin ; Water

Korl:ICR mice, established by the Korean National Institute of Food and Drug Safety Evaluation (NIFDS), are characterized based on their genetic variation, response to gastric injury, and response to constipation inducers. To compare the inhibitory responses of ICR stocks obtained from three different sources to the anticancer drug cisplatin (Cis), alterations in tumor volume, histopathological structure, and toxicity were examined in Sarcoma 180 tumor-bearing Korl:ICR, A:ICR (USA source), and B:ICR (Japan source) mice treated with low and high concentrations of Cis (L-Cis and H-Cis, respectively). Tumor size and volume were lower in H-Cis-treated mice than in L-Cis-treated mice in all three ICR stocks with no significant differences among stocks. There was a significant enhancement of the necrotizing areas in the histological structures in the L-Cis- and H-Cis-treated groups relative to that in the untreated group. The necrotizing area changes were similar in the Sarcoma 180 tumor-bearing Korl:ICR, A:ICR, and B:ICR mice. However, there were stock-bases differences in the serum biomarkers for liver and kidney toxic effects. In particular, the levels of AST, ALT and BUN increased differently in the three H-Cis-treated ICR stocks, whereas the levels of ALP and CRE were constant. Taken together, the results of the present study indicate that Korl:ICR, A:ICR, and B:ICR mice have similar overall inhibitory responses following Cis treatment of Sarcoma 180-derived solid tumors, although there were some differences in the magnitude of the toxic effects in the three ICR stocks.
Animals ; Biomarkers ; Cisplatin ; Constipation ; Genetic Variation ; Kidney ; Liver ; Mice ; Mice, Inbred ICR* ; Sarcoma ; Sarcoma 180 ; Tumor Burden

C57BL/6N is the most widely used inbred mouse strain applied in a wide variety of research areas including cancer, cardiovascular biology, developmental biology, diabetes and obesity, genetics, immunology, neurobiology, and sensorineural research. To compare the fertilization rates of C57BL/6NKorl mice with two commercial C57BL/6N stocks, differences in reproductive organ structures, sperm and egg numbers, fertilization rates, and embryo development rates among C57BL/6NKorl (Korea FDA source), C57BL/6NA (USA source), and C57BL/6NB (Japan source) mice were determined. Among the stocks, no significant differences were detected in organ weight and histological structure of male and female reproductive organs, although body weight was higher in C57BL/6NKorl mice than that in the other groups. The concentration and morphology of sperm and eggs in C57BL/6NKorl mice were similar to those of C57BL/6NA and C57BL/6NB mice. Furthermore, the three stocks had similar in vitro fertilization and embryo development rates, although these rates tended to be higher in C57BL/6NB mice. Pup body weight was higher in C57BL/6NKorl and C57BL/6NB mice than that in C57BL/6NA mice. The results of the present study suggest that C57BL/6NKorl, C57BL/6NA, and C57BL/6NB mice obtained from three different sources have similar fertilization and embryo development rates, although there were slight differences in the magnitude of their responses rates.
Allergy and Immunology ; Animals ; Biology ; Body Weight ; Developmental Biology ; Eggs ; Embryonic Development ; Female ; Fertilization in Vitro ; Fertilization* ; Genetics ; Humans ; Male ; Mice* ; Mice, Inbred Strains ; Neurobiology ; Obesity ; Organ Size ; Ovum ; Pregnancy ; Spermatozoa

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