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The pathological significance of DNA damage-inducible transcript 3 immunohistochemistry in the diagnosis of myxoid liposarcoma.

BACKGROUND: Myxoid liposarcoma (MLS) is a distinct subtype of liposarcoma characterised by recurrent FUS-DDIT3 or EWSR1-DDIT3 gene fusions and distinctive histological features. DNA damage-inducible transcript 3 (DDIT3) is a key downstream mediator of these fusions and contributes to sarcoma development by disrupting adipocytic differentiation. In this study, we assessed the diagnostic value and biological relevance of DDIT3 by combining immunohistochemistry (IHC) with quantitative real-time polymerase chain reaction (qRT-PCR). METHODS: The study included 128 soft tissue tumours, comprising 4

Rapamycin and Cyclosporin A Alleviate Bone Marrow Adiposity in Murine Model of Aplastic Anemia.

BACKGROUND: Aplastic anemia (AA) is a bone marrow failure disease characterized by immune-mediated destruction of hematopoietic stem and progenitor cells. Bone marrow adiposity represents a typical pathological manifestation observed in AA. METHODS: The aim of this study was to establish a murine model of AA using immune-mediated methods and assess the impact of rapamycin (Rapa) and cyclosporin A (CsA) on bone marrow adiposity. The AA murine model was induced by 137Cs γ-ray irradiation and allogeneic lymphocyte infusion. Rapamycin and cyclosporine were administered intraperitoneally. Hematolo

Potential Role for the Ubiquitin Ligase SIAH2 in Modulating Bone Morphology and Adiposity.

Marrow adipose expansion, with obesity or ageing, increases fracture risk. Skeletal stem cells can commit to osteoblast or adipocyte endpoints, an inverse relationship influenced by peroxisome proliferator-activated receptor gamma (PPARγ). Seven in absentia homologue 2 (SIAH2) is a ubiquitin ligase that acts in peripheral adipose tissue stromal progenitors, promoting PPARγ activity and adipogenesis. The pivotal role of PPARγ in bone marrow adipose tissue accumulation prompted us to evaluate SIAH2's role in the balance between osteogenesis and adipogenesis. Using adherent skeletal stem and/or p

Low-dose tamoxifen ameliorates ovariectomy-induced metabolic and immune dysfunction.

The decline in estrogen following menopause is a major driver of metabolic and immune dysfunction in aging females. While hormone replacement therapy improves many of these outcomes, its clinical use remains limited due to concerns regarding estrogen-sensitive malignancies. Tissue-selective estrogen complexes (TSECs), which combine estrogens with selective estrogen receptor modulators (SERMs) such as tamoxifen (TAM), represent a promising strategy to preserve the metabolic and immunological benefits of estrogen while reducing oncogenic risk. However, the systemic effects of TAM under condition

Clinical and lipid metabolic responses to diacylglycerol oil administration in Chinese adults with overweight/obesity or central obesity: a randomized, double-blind, placebo-controlled trial.

Abnormalities in triacylglycerol metabolism can lead to excessive visceral fat accumulation. Though diacylglycerol (DAG) administration could reduce serum total triacylglycerol (TG), its impact on visceral fat deposition and potential mechanisms remains unclear. This trial aimed to evaluate the impact of substituting regular rapeseed cooking oil (TAG) with DAG oil on primary outcomes such as anthropometric measurements and lipid profiles, as well as secondary outcomes including visceral fat and serum lipidomics in Chinese adults with overweight/obesity or central obesity. Ninety-five participa

Immune reprogramming in the bone marrow microenvironment: a new perspective on the bone immune microenvironment of postmenopausal osteoporosis.

Research on postmenopausal osteoporosis (PMOP), a common bone metabolic disease, has traditionally focused on bone loss and imbalance in bone remodeling. However, with the development of bone immunology, the complex interactions between immune cells and bone cells in the bone marrow microenvironment have gradually been revealed, and "immune reprogramming" is considered a key factor driving the persistent bone loss in PMOP. Current evidence indicates that the postmenopausal bone marrow microenvironment undergoes significant structural and functional changes. These changes are characterized by a

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… Certain receptors on adipocytes, such as the activation or inhibition of the CD40 signaling pathway, can also regulate the function of bone marrow immune cells, affecting bone metabolism and the state of adipocytes ( 83 ). … Adipocytes secrete adipokines (such as leptin, adiponectin), and inflammatory mediators (TNF-α, IL-6, IL-1β), which alter the differentiation of BMSCs, inhibit osteoblast differentiation, and promote adipocyte activity and osteoclast activation. …

Immunomodulatory effects of cannabis use: a multi-omics study in people living with HIV.

BACKGROUND: Cannabis is one of the most commonly used substances worldwide. Cannabinoids are known to have anti-inflammatory effects. However, cannabis is mainly smoked, resulting in exposure to reactive particles, toxins and oxidants, inducing pro-inflammatory effects. Because the net immunological effect of cannabis use on systemic inflammation and immune function has barely been studied in humans, we assessed this in a large cohort of people living with HIV (PLHIV), while taking into account the effects of tobacco use. METHODS: This cross-sectional study was performed in 1895 PLHIV on anti

Early-in-life inhalation of ferrocene-derived diesel exhaust-induced metabolic and small intestinal toxicities: Roles of peroxisome proliferator-activated receptor gamma and ferroptosis.

Ferrocene-derived diesel exhaust (FDE) had been demonstrated to exhibit enhanced cardiopulmonary toxicities. This study evaluated the potential metabolic and small intestinal toxicities following early-in-life inhalation exposure to FDE using an in ovo air cell inhalation model in chicken embryos. Ferrocene was added to standard diesel fuel at 205, 410 or 820 mg/L (corresponding to 75, 150 or 300 ppm iron) and combusted in a diesel generator. The resulting FDE was exposed to embryonic day 18-19 chicken embryos via air cell inhalation. Serum, small intestine, white adipose tissue, and pancreas

Orosomucoid 2 improves reproductive phenotypes in a mouse model of PCOS induced by letrozole under high-fat diet conditions.

Polycystic ovary syndrome (PCOS) is the most common reproductive endocrine disorder among women of reproductive age. It is characterized by excess androgens, anovulation, and polycystic ovarian morphology, and is often accompanied by obesity, insulin resistance, and glucose metabolism abnormalities. Although PCOS is a complex disease with diverse and uncertain etiologies, metabolic dysfunction and adipose tissue abnormalities are critical components in its pathology. Previous studies have demonstrated that letrozole exposure combined with high-fat diet treatment in female mice produced key end

Effects of Swimming at Different Water Temperatures on Muscle and Adipose Tissue Adaptation in Diet-Induced Obese Mice.

BACKGROUND: Obesity is a major global health concern, leading to increased risk of metabolic diseases and mortality. Swimming, as a low-impact exercise, may provide metabolic benefits. However, the influence of water temperature on the metabolic and physiological responses remains underexplored. This study investigated the effects of water temperatures on muscle and adipose tissue adaptations in high-fat diet-induced obese mice. METHODS: Obese mice were subjected to swimming at different water temperatures: 15°C, 25°C, or 32°C. Changes in body and tissue weight, grip strength, exhaustive swim

Selective PPARα Modulator Pemafibrate Ameliorates Metabolic Dysfunction-Associated Steatotic Liver Disease Through Regulation of Leptin Signaling and Remodeling of Gut Microbiota.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is one of the leading causes of chronic liver disease worldwide, and effective pharmacological therapies remain limited. Pemafibrate (Pema), a selective peroxisome proliferator-activated receptor alpha (PPARα) modulator (SPPARMα), has shown promising therapeutic potential in patients with MASLD and hypertriglyceridemia; however, its underlying mechanisms remain incompletely understood. Here, we investigated the therapeutic effects and molecular mechanisms of Pema using in vitro and in vivo MASLD models and evaluated its clinical

In Silico ApoE Isoform Interactions with Methylmercury (MeHg) and In Vivo MeHg Intoxication Effects on Epididymal White Fat Tissue and Liver Function in Young ApoE Knockout Mice.

MeHg neurotoxicity is well recognized; however, less is known about its effects on metabolism. Here, we integrated in silico and in vivo approaches to investigate MeHg interactions with apolipoprotein E (ApoE) and their metabolic consequences. Computational analyses revealed that human ApoE2 and ApoE3 isoforms establish stable Hg-S bonds with MeHg, while ApoE4 showed no stable binding, suggesting reduced mercury retention capacity. In addition, we evaluated the impact of MeHg intoxication (20 mg/L in drinking water for 20 days) on the liver and epididymal white fat (EWF) in young ApoE knockout

Relationship Between Hypovitaminosis C, Obesity, and Features of Metabolic Syndrome-A Narrative Review.

This narrative review aimed to review plausible mechanisms for the role of vitamin C (ascorbic acid [AA]) in the maintenance of healthy weight and energy metabolism; examine the evidence for inadequate vitamin C (plasma AA <50 µmol/L), hypovitaminosis C (≤23 µmol/L), and vitamin C deficiency (≤11.4 µmol/L) in the disrupted homeostasis of obesity and metabolic syndrome; and ascertain whether vitamin C supplementation or dietary intervention could potentially treat obesity and the associated features of metabolic syndrome. Vitamin C hypovitaminosis and deficiency are prevalent in developed count

Gastrointestinal involvement in Ehlers-Danlos syndrome classical-like type 2 associated with a novel AEBP1 splice-site variant.

Ehlers-Danlos syndrome classical-like type 2 (clEDS2) is a rare autosomal recessive connective tissue disorder caused by biallelic loss-of-function variants in the gene encoding adipocyte enhancer-binding protein 1 (AEBP1). While cutaneous and skeletal manifestations are commonly observed, gastrointestinal complications, including bowel rupture, have been reported only rarely, and their histopathological basis remains poorly characterized. Here, we report findings of molecular investigations, gastrointestinal histopathological evaluation, and long-term clinical follow-up in the 16th reported p

Lactational Enrofloxacin Exposure Promotes Offspring Lipid Metabolic Disorder and Adiposity Involving Gut Microbiota-Derived LPS and PPARγ Signaling.

Early-life antibiotic exposure is a critical environmental trigger for developmental metabolic disorders and long-term obesity risk. Lactational enrofloxacin exposure exerts potential metabolic programming toxicity, but its long-term effects and underlying mechanisms remain poorly defined. This study aimed to investigate the persistent influences of lactational enrofloxacin exposure on postnatal growth, lipid metabolism and adipogenesis in mouse offspring and explore the potential gut microbiota-associated regulatory mechanism. A combined in vivo and in vitro approach was utilized. In vivo mou

TUG-891-mediated FFAR4 activation attenuates vascular remodeling via suppression of aberrant browning and lipolysis in perivascular adipose tissue.

BACKGROUND: Free fatty acid receptor 4 (FFAR4) activation modulates adipogenesis, but this pathway has not been explored in the context of perivascular adipose tissue (PVAT) dysfunction and vascular remodeling. METHODS: Adipose tissue-specific FFAR4 knockout (Adipo-Ffar4-/-, Adipo-KO) mice were generated by crossing Adipoq-Cre and Ffar4flox/flox (WT) mice. FeCl₃-induced PVAT injury model in abdominal aorta was established. TUG-891 (20 mg/kg/day, i.p.) was administered for 4 weeks. In vitro, FeCl₃-conditioned medium was prepared with mouse PVAT explants. Proliferation and migration of vascular

Resolution of Recurrent Severe Hypoglycemia After Surgical Excision of a Primary Hepatic Neoplasm of Uncertain Histogenesis in a Dog: A Case Report.

Primary hepatic neoplasms in dogs, while uncommon, are occasionally associated with severe hypoglycemia, although the underlying mechanism may be difficult to establish. A 7-year-old castrated male Maltese dog weighing 3.6 kg was referred for recurrent bilateral pelvic limb weakness, episodic collapse, and abdominal distension. Severe hypoglycemia was documented, with a blood glucose concentration of 26 mg/dL. Computed tomography revealed a large mass arising from the right lateral liver lobe, with no identifiable pancreatic mass or distant metastasis. The serum insulin concentration measured

PPARγ suppresses the tumorigenesis of retroperitoneal liposarcoma via inactivation of the PI3K/AKT signaling pathway.

BACKGROUND: Retroperitoneal liposarcoma (RLPS) is characterized by high heterogeneity, frequent recurrence and dismal prognosis. Surgery remains the main therapeutic strategy, while no effective targeted therapy is available for advanced RLPS. Peroxisome proliferator-activated receptor γ (PPARγ) is a core regulator of adipocyte differentiation, yet its function and regulatory mechanisms in RLPS remain unclear. METHODS: Eighty clinical specimens and information from RLPS patients were collected and analyzed to examine PPARγ expression and assess its prognostic value, integrated with results fr

Elucidating the pathogenesis of rumen abnormal adipose deposition in high-concentrate fed Hu sheep through transcriptomic profiling.

BACKGROUND: Abnormal ruminal fat accumulation is a significant rumen health problem under high-concentration feeding regimes. However, the pathogenesis of abnormal ruminal fat accumulation remains poorly understood, the determinants of inter-individual variability are undetermined, and the incidence is relatively high. METHODS: This study assessed the incidence of abnormal ruminal adipose deposition in 326 fattening Hu lambs and conducted comparative analyses between lesion (LG) and normal (NG) groups. Production performance and feed intake were monitored over a 100-day trial. At slaughter (1

Myeloid AEG-1/MTDH drives inflammation and hepatocellular dysfunction in diet-induced steatohepatitis.

Astrocyte elevated gene-1 (AEG-1)/metadherin plays an important role in regulating lipid metabolism and inflammation in hepatocytes and promotes metabolic dysfunction-associated steatohepatitis (MASH). Myeloid cells, such as macrophages, play a key role in regulating inflammation. Here, we investigated the role of AEG-1 in myeloid cells in regulating high fat)/high sugar diet (HF/HSD)-induced MASH. Littermates of myeloid cell-specific AEG-1 knockout mice (AEG-1ΔMAC) and AEG-1 floxed mice (AEG-1fl/fl) were fed either a control diet or an HF/HSD for 20 weeks. Both male and female AEG-1ΔMAC mice