Mitochondrial substrate oxidation regulates distinct cell differentiation outcomes.

Mitochondrial metabolism, signaling, and dynamics are key regulators of cell fate. While glycolysis supports stemness, mitochondrial expansion and oxidative phosphorylation (OXPHOS) facilitate differentiation. This forum presents emerging evidence that the type of substrate, whether amino acids, carbohydrates, or fatty acids, oxidized by mitochondria significantly influences differentiation outcomes.

4-hydroxybenzoic acid induces browning of white adipose tissue through the AMPK-DRP1 pathway in HFD-induced obese mice.

Background: Beige adipocytes have physiological functions similar to brown adipocytes, which are available to increase energy expenditure through uncoupling protein 1 (UCP1) within mitochondria. Recently, many studies showed white adipocytes can undergo remodeling into beige adipocytes, called "browning", by increasing fusion and fission events referred to as mitochondrial dynamics.

Purpose: In this study, we aimed to investigate the browning effects of 4-hydroxybenzoic acid (4-HA), one of the major compounds of black raspberries.

FXR-ApoC2 pathway activates UCP1-mediated thermogenesis by promoting the browning of white adipose tissues.

FXR, encoded by Nh1r4, is a nuclear receptor crucial in regulating bile acid, lipid, and glucose metabolism. Prior research has indicated that activating FXR in the liver and small intestine may offer protection against obesity and metabolic diseases. This study demonstrates the essential role of the FXR-ApoC2 pathway in promoting the browning of white adipose tissue (WAT).

Systemic inhibition of purine biosynthesis prevents weight gain and improves metabolic health by increasing thermogenesis and decreasing food intake.

Objective: Obesity is a major health concern, largely because it contributes to type 2 diabetes mellitus (T2DM), cardiovascular disease, and various malignancies. Increase in circulating amino acids and lipids, in part due to adipose dysfunction, have been shown to drive obesity-mediated diseases. Similarly, elevated purines and uric acid, a degradation product of purine metabolism, are found in the bloodstream and in adipose tissue.

Disruption of nucleotide biosynthesis reprograms mitochondrial metabolism to inhibit adipogenesis.

A key organismal response to overnutrition involves the development of new adipocytes through the process of adipogenesis. Preadipocytes sense changes in the systemic nutrient status and metabolites can directly modulate adipogenesis. We previously identified a role of de novo nucleotide biosynthesis in adipogenesis induction, whereby inhibition of nucleotide biosynthesis suppresses the expression of the transcriptional regulators PPARγ and C/EBPα.

Loss of tumor suppressors promotes inflammatory tumor microenvironment and enhances LAG3+T cell mediated immune suppression.

Low response rate, treatment relapse, and resistance remain key challenges for cancer treatment with immune checkpoint blockade (ICB). Here we report that loss of specific tumor suppressors (TS) induces an inflammatory response and promotes an immune suppressive tumor microenvironment. Importantly, low expression of these TSs is associated with a higher expression of immune checkpoint inhibitory mediators.

Epigallocatechin gallate protects against fat and muscle atrophy in B16BL6 melanoma-bearing mice on a high-fat diet.

Aims: Epidemiological evidence indicates that there is a substantial association between body mass index (BMI) and at least ten forms of cancer, including melanoma, and BMI imbalance contributes to the poor survival rate of cancer patients before and after therapy. Nevertheless, few pharmacological studies on models of obesity and cancer have been reported. In this study, we administered epigallocatechin gallate (EGCG) to B16BL6 tumor-bearing mice that received a high-fat diet (HFD) to examine its impact.

var. Induces a Macrophage M2-Like Phenotype Mediated by Nrf2/HO-1 in LPS-Stimulated Macrophages.

var. (CAAE), which is in the genus L. (Solanaceae), was found to be richer in polyphenols and flavonoids than other prevalent peppers of var.

Moderating AKT signaling with baicalein protects against weight loss by preventing muscle atrophy in a cachexia model caused by CT26 colon cancer.

Cancer cachexia is a type of energy-wasting syndrome characterized by fatigue, anorexia, muscle weakness, fat loss, and systemic inflammation. Baicalein, a flavonoid with bioactive properties, has demonstrated the ability to mitigate cardiac and skeletal muscle atrophy in different experimental settings. This effect is achieved through the inhibition of muscle proteolysis, suggesting its potential in preserving skeletal muscle homeostasis.

C.A. meyer alleviates benign prostatic hyperplasia while preventing finasteride-induced side effects.

C.A. Meyer, a widely used traditional medicine in East Asia, shows many beneficial effects on immune function, male erectile dysfunction, cancer, excessive oxidants, and aging issues.

Anmyungambi Decoction Ameliorates Obesity through Activation of Non-Shivering Thermogenesis in Brown and White Adipose Tissues.

Obesity is a burden to global health. Non-shivering thermogenesis of brown adipose tissue (BAT) and white adipose tissue (WAT) is a novel strategy for obesity treatment. Anmyungambi (AMGB) decoction is a multi-herb decoction with clinical anti-obesity effects.

Polysaccharides from leaves protect against cisplatin‑induced cytotoxicity in macrophages by alleviating mitochondrial dysfunction.

Cisplatin is a prominent chemotherapeutic agent that can induce significant damage to normal cells. Therefore, it is important to develop agents that protect normal cells without influencing the chemotherapeutic effect of cisplatin. The present study was conducted to explore the protective effects of leaf polysaccharides (ALPS) against cisplatin‑induced toxicity in macrophages.

Therapeutic role of Glycyrrhiza Uralensis fisher on benign prostatic hyperplasia through 5 alpha reductase regulation and apoptosis.

Background: Benign prostatic hyperplasia (BPH) is an age-related disease in adult men. There are two pharmacological treatments for BPH. However, these synthetic materials have various risks, many studies are being conducted to develop new drugs from natural sources.

DNA Methyltransferase 3B-Mediated Intratumoral Heterogeneity and Therapeutic Targeting in Breast Cancer Recurrence and Metastasis.

Unlabelled: The mechanisms of how cancer cells are selected and evolve to establish distant metastatic colonies remain unclear. Tumor heterogeneity and lack of biomarkers are some of the most difficult challenges in cancer biology and treatment. Here using mouse models for triple-negative breast cancer (TNBC) metastasis, we report heterogeneous expression of DNA methyltransferase 3B (DNMT3B) in both mouse and human primary tumors.

R1 Lysate Induces Tolerogenic Maturation in Lipopolysaccharide-Stimulated Dendritic Cells and Protects Dextran Sulfate Sodium-Induced Colitis in Mice.

is an extremophilic bacterium that can thrive in harsh environments. This property can be attributed to its unique metabolites that possess strong antioxidants and other pharmacological properties. To determine the potential of R1 lysate (DeinoLys) as a pharmacological candidate for inflammatory bowel disease (IBD), we investigated the anti-inflammatory activity of DeinoLys in bone marrow-derived dendritic cells (BMDCs) and a colitis mice model.

Ellagic acid improves benign prostate hyperplasia by regulating androgen signaling and STAT3.

Benign prostate hyperplasia (BPH) is an age-related disease in men characterized by the growth of prostate cells and hyperproliferation of prostate tissue. This condition is closely related to chronic inflammation. In this study, we highlight the therapeutic efficacy of ellagic acid (EA) for BPH by focusing on the AR signaling axis and STAT3.

Raphani Semen ( L.) Ameliorates Alcoholic Fatty Liver Disease by Regulating De Novo Lipogenesis.

In this study, we investigated the pharmacological effect of a water extract of Raphani Semen (RSWE) on alcoholic fatty liver disease (AFLD) using ethanol-induced AFLD mice (the NIAAA model) and palmitic acid (PA)-induced steatosis HepG2 cells. An RSWE supplement improved serum and hepatic triglyceride (TG) levels of AFLD mice, as well as their liver histological structure. To explore the molecular action of RSWE in the improvement of AFLD, we investigated the effect of RSWE on four major pathways for lipid homeostasis in the liver: free fatty acid transport, lipogenesis, lipolysis, and β-oxidation.

Fruit of Induces Mitochondrial Activation and Non-Shivering Thermogenesis through Regulation of PPARγ.

The extract of the fruit (GJFE) can been consumed as an herbal tea or used as a yellow dye. Recently, studies report that GFJE exerts inhibitory effects on lipid accumulation and adipogenesis in white adipocytes. We evaluated the thermogenic actions of GJFE by focusing on mitochondrial activation and studying the underlying mechanisms.

PEX13 is required for thermogenesis of white adipose tissue in cold-exposed mice.

Non-shivering thermogenesis (NST) is a heat generating process controlled by the mitochondria of brown adipose tissue (BAT). In the recent decade, 'functionally' acting brown adipocytes in white adipose tissue (WAT) has been identified as well: the so-called process of the 'browning' of WAT. While the importance of uncoupling protein 1 (UCP1)-oriented mitochondrial activation has been intensely studied, the role of peroxisomes during the browning of white adipocytes is poorly understood.

Ellagic acid induces beige remodeling of white adipose tissue by controlling mitochondrial dynamics and SIRT3.

To determine whether ellagic acid (EA) induces the "beige remodeling" of white adipose tissue (WAT), we treated cold-exposed mice and mouse stromal vascular fraction (SVF) cells with EA, a phytochemical abundant in fruits and vegetables, in particular berries. We then investigated the mechanism of EA in beige remodeling with a particular focus on DRP1-mediated mitochondrial fission and SIRT3. EA induced the trans-differentiation of white adipocytes to beige adipocytes by promoting the expression of UCP1 and other brown and beige adipocytes/fat factors (PRDM16, UCP1, PGC1α, CD137, and TBX1) and mitochondrial dynamics-related factors (SIRT3, NRF1, CPT1β, DRP1, and FIS1) in 3T3-L1/SVF cells, and these were confirmed in the inguinal WAT of a cold-exposed mouse model.

Chrysin Derivative CM1 and Exhibited Anti-Inflammatory Action by Upregulating Toll-Interacting Protein Expression in Lipopolysaccharide-Stimulated RAW264.7 Macrophage Cells.

Although our previous study revealed that gamma-irradiated chrysin enhanced anti-inflammatory activity compared to intact chrysin, it remains unclear whether the chrysin derivative, CM1, produced by gamma irradiation, negatively regulates toll-like receptor (TLR) signaling. In this study, we investigated the molecular basis for the downregulation of TLR4 signal transduction by CM1 in macrophages. We initially determined the appropriate concentration of CM1 and found no cellular toxicity below 2 μg/mL.

HMOC, a chrysin derivative, induces tolerogenic properties in lipopolysaccharide-stimulated dendritic cells.

Although we previously identified a new hydroxymethoxyl chrysin derivative (HMOC) using ionizing radiation, the anti-inflammatory mechanism of HMOC in dendritic cells remains unclear. In this study, we investigate the effects of HMOC on phenotypic and functional changes in activated bone marrow-derived dendritic cells (BMDCs). In lipopolysaccharide (LPS)-stimulated BMDCs, HMOC treatment inhibited pro-inflammatory cytokines (TNF-α, IL-12p70, and IL-1β), surface molecules (CD80, CD86, MHC-I, and MHC-II), and antigen-presentation to MHC-I and II without a decrease in IL-10.