Результаты поиска

Metabolic checkpoints in rheumatoid arthritis.

BACKGROUND: Rheumatoid Arthritis is a systemic autoimmune disease affecting 0.5-1 % of the population. Despite a growing therapeutic armamentarium, RA remains incurable, and many patients suffer significant morbidity over time. The strongest genetic risk derives from HLA class II polymorphisms, implicating T cells as pathogenic drivers. Innate immune cells, e.g. monocytes and macrophages (Mⱷ) contribute to chronic tissue inflammation through an array of pro-inflammatory functions but also present antigen to autoreactive T cells. Differentiation, survival, and effector functions of both T cells

The role of ferroptosis-related genes for overall survival prediction in breast cancer.

BACKGROUND: Ferroptosis is a novel iron-dependent form of cell death, which is implicated in various diseases including cancers. However, the influence of ferroptosis-related genes on the prognosis of breast cancer remains unclear. METHODS: RNA sequencing data of 1053 breast cancer tissue samples and 111 normal tissue samples from The Cancer Genome Atlas (TCGA) were analyzed. Expression levels of 259 ferroptosis-related genes were compared. Gene Ontology (GO) and the Kyoto Gene and Genomic Encyclopedia (KEGG) analyses were conducted on differentially expressed genes. Cox univariate analysis w

Pathogenesis of non-alcoholic fatty liver disease mediated by YAP.

OBJECTIVE: This study aimed to investigate the mechanism of the interaction between Yes-associated protein (YAP) and transforming growth factor-β (TGF-β)/Smad signaling pathways in the development of non-alcoholic fatty liver disease (NAFLD). METHODS: Serum samples of monkeys with biopsy-proven NAFLD and healthy normal monkeys were used to measure fasting plasma glucose (FPG), low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglyceride (TG) and albumin (ALB) with the BECKMAN CX5 PRO. Hematoxylin-eosin staining (H&E) was used for pathologic analysis, Masson trichrome staining w

Cell-penetrating Peptide-modified Targeted Drug-loaded Phase-transformation Lipid Nanoparticles Combined with Low-intensity Focused Ultrasound for Precision Theranostics against Hepatocellular Carcinoma.

Objective: Prepare a multifunctional ultrasound molecular probe, hyaluronic acid-mediated cell-penetrating peptide-modified 10-hydroxycamptothecin-loaded phase-transformation lipid nanoparticles (HA/CPPs-10-HCPT-NPs), and to combine HA/CPPs-10-HCPT-NPs with low-intensity focused ultrasound (LIFU) for precision theranostics against hepatocellular carcinoma (HCC). Methods: HA/CPPs-10-HCPT-NPs were prepared using thin-film dispersion, ultrasound emulsification, and electrostatic effects. HA/CPPs-10-HCPT-NPs were characterized for particle size, zeta potential, encapsulation efficiency and drug-lo

Small Oscillatory Rheology: Evaluating Microstructure and Component Interactions in Different Food Systems.

Food has been categorized as solid, molecular dispersion, colloidal (e.g., emulsions, gels, sols), and coarse dispersion that exhibit unique rheological behavior driven by polysaccharides, proteins, and lipids. These compounds exhibit various functional attributes such as texture, stability, and sensory quality. During processing, starch gelatinize, proteins denature and coagulate, and fat droplets interact with biopolymers to form viscoelastic or structured networks. These molecular and microstructural changes directly influence rheological behavior. Small-amplitude oscillatory shear (SAOS) r

A high-concentrate diet induces an inflammatory response and oxidative stress and depresses milk fat synthesis in the mammary gland of dairy cows.

Although high-concentrate diet feeding can temporarily increase milk production, it can cause a series of metabolic diseases, such as subacute ruminal acidosis (SARA) and milk fat depression. The main purpose of this experiment was to study the effects of a high-concentrate diet on the inflammatory response, oxidative stress, and milk fat synthesis in the mammary gland of dairy cows. Twelve Holstein cows equipped with rumen fistulas were randomly divided into 2 groups, each with 6 cows, fed a low-concentrate diet (LC) and a high-concentrate diet (HC). On d 20 and 21 of the experiment, rumen fl

Rumen-protected choline reduces hepatic lipidosis by increasing hepatic triacylglycerol-rich lipoprotein secretion in dairy cows.

Objectives were to determine the effects of supplementing rumen-protected choline (RPC) on hepatic composition and secretion of triacylglyce … nscripts associated with mitochondrial oxidation of fatty acids (HADHA, MLYCD) and stabilization of lipid droplets (PLIN2). After infusion of tyloxapol, RPC increased the AUC for serum triacylglycerol (21,741 vs. 32,323 vs. 28,699 ± 3,706 mg/dL × min) and VLDL cholesterol (4,348 vs. 6,465 vs. 5,740 ± 741 mg/dL × min) but tended to reduce the concentrations of tr …

Research on the mechanism of regulating spleen-deficient obesity in rats by bawei guben huashi jiangzhi decoction based on multi-omics analysis.

ETHNOPHARMACOLOGY RELEVANCE: Bawei Guben Huashi Jiangzhi Decoction (BGHJ), a traditional Chinese compound formula, comprises eight Chinese medicinal herbs: Codonopsis Radix, Atractylodis Macrocephalae Rhizoma, Cassiae Semen, Lysimachiae Herba, Edgeworthiae Gardner Flos, Oryzae Semen cum Monasco, Nelumbinis Folium, and Alismatis Rhizoma. It has the therapeutic effects of improving digestive and absorptive functions of the gastrointestinal tract, reducing cholesterol levels, and helping to lose weight. Therefore, BGHJ is mainly used to treat spleen-deficient obesity (SDO) clinically. AIM OF THE

Clinical and molecular features of ovarian stimulation in peripubertal girls with mosaic Turner's syndrome.

STUDY QUESTION: Do peripubertal girls with mosaic Turner's syndrome (TS) respond to ovarian stimulation (OS) for oocyte freezing as adult wo … erns of the steroidogenic enzymes and their co-localization with mitochondria and cholesterol-laden lipid droplets. LIMITATIONS, REASONS FOR CAUTION: Findings were obtained from a limited number of mosaic TS patients. It is unclear if these findings are reproducible in non-mosaic peripubertal cases. Furthermore, no data are available yet regarding the post-thaw …

Ovary organization and oogenesis in two species of cave-living clitellate annelids from the genus Delaya (Clitellata, Pelodrilidae).

Clitellate annelids (Clitellata) are hermaphrodites with gonads localized in specific segments in the anterior body part. Localization of go … ough several body segments (XII-XV). Delaya produces mesolecithic eggs with prominent yolk spheres, lipid droplets, and glycogen granules. Only some minor differences were observed between the two studied species. The most notable difference concerns the cytophore shape and volume in cysts connecting nurse cells. In Delaya sp. FR, the cytophore is reticular and …

Reactive oxygen species/c-Jun N-terminal kinase/nuclear factor kappa-B signaling molecules are involved in pe-riodontitis-induced liver injury by regulating apoptosis.

OBJECTIVES: The occurrence and development of periodontitis and nonalcoholic fatty liver disease (NAFLD) are closely related to the accumula … ridge bone was obvious and liver tissue structure was destroyed, with balloon-like changes and red lipid droplets. MitoSOX red staining results showed that the ROS level was significantly higher in the liver tissue of the periodontitis group than in that of the control group. Biochemical test results showed that the aspartate aminotransferase (AST) and alanine …

[Role of brain and muscle ARNT-like protein 1 in the rat periodontitis-induced liver injury model].

Objective: Brain and muscle ARNT-like protein 1 (BMAL1) is a core component of hepatocyte molecular clock and plays an important role in the … infiltrated inflammatory cells in the liver tissue, disorganized liver cords and a large number of lipid droplets formed in the hepatocytes of the periodontitis group compared with the control group. The results of serum biochemical assay showed that the levels of GOT [(62.77±2.59) U/L], GPT [(47.54±1.04) U/L], TC [(3.19±0.23) mmol/L] and TG [(1.11±0.09) mmol/L …

Evaluation of a two-generation reproduction toxicity study adding endpoints to detect endocrine disrupting activity using vinclozolin.

A two-generation reproduction toxicity study in rats adding extra endpoints to detect endocrine disrupting activity was conducted using vinc … bular hepatocellular hypertrophy in males at 200 and 1000 ppm and in females at 1000 ppm, increased lipid droplets in the adrenal zona fasciculata and zona glomerulosa in males at 200 and 1000 ppm and in females at 40 ppm and above, and hyperplasia of ovarian interstitial cells and vacuolation of lutein cells in females at 1000 ppm in both generations. Almost al …

The duration of embryo culture after mouse IVF differentially affects cardiovascular and metabolic health in male offspring.

STUDY QUESTION: Do the long-term health outcomes following IVF differ depending upon the duration of embryo culture before transfer? SUMMARY ANSWER: Using a mouse model, we demonstrate that in male but not female offspring, adverse cardiovascular (CV) health was more likely with prolonged culture to the blastocyst stage, but metabolic dysfunction was more likely if embryo transfer (ET) occurred at the early cleavage stage. WHAT IS KNOWN ALREADY: ART associate with increased risk of adverse CV and metabolic health in offspring, and these findings have been confirmed in animal models in the ab

[Effects of electroacupuncture of different intensities and durations on PERK/ATF4/CHOP signaling pathway in liver of non-alcoholic fatty liver disease rats].

OBJECTIVES: To analyze the effects of electroacupuncture (EA) at "Fenglong" (ST40) and "Zusanli" (ST36) of different intensities and duratio … at liver tissue. RESULTS: In the high-fat model group, there was a significant accumulation of red lipid droplets in the liver cells, which was reduced significantly in the SEA group at the 4th week. Compared with the normal diet group with the same treatment duration, the contents of serum ALT, AST, and the expression of PERK, ATF4, and CHOP mRNAs and proteins …

[Notch1 inhibits the mechanistic role of STING signaling to regulate hepatocyte lipophagy in nonalcoholic steatohepatitis].

Objective: To study the mechanistic role of myeloid-specific Notch1 knockout inhibiting STING signaling to regulate hepatocyte lipophagy. Methods: A mouse model of nonalcoholic steatohepatitis (NASH) was established using a high-fat diet (HFD) and mouse bone marrow-derived macrophages (BMMs). Primary hepatocytes were isolated to construct a co-culture system. Twelve Notch1(FL/FL) mice were randomly divided into two groups: the Notch1(FL/FL) + normal diet (NCD) and the Notch1(FL/FL) + HFD group. Further, 12 Notch1(M-KO) mice were randomly divided into two groups: Notch1(M-KO) + NCD, and Notch1(

Cancer Cell Metabolism in Hypoxia: Role of HIF-1 as Key Regulator and Therapeutic Target.

In order to meet the high energy demand, a metabolic reprogramming occurs in cancer cells. Its role is crucial in promoting tumor survival. Among the substrates in demand, oxygen is fundamental for bioenergetics. Nevertheless, tumor microenvironment is frequently characterized by low-oxygen conditions. Hypoxia-inducible factor 1 (HIF-1) is a pivotal modulator of the metabolic reprogramming which takes place in hypoxic cancer cells. In the hub of cellular bioenergetics, mitochondria are key players in regulating cellular energy. Therefore, a close crosstalk between mitochondria and HIF-1 underl

Совпадение в полном тексте источника
… Interestingly, primary renal cell carcinoma revealed a correlation between HIF-2α (but not HIF-1α) and generation of lipid droplets (see Section 3.3 ). … Another aspect of lipid metabolism concerns the lipid droplets’ composition. …

Оптимизированная внутриназальная доставка сегестерона ацетатата в мозг с использованием наноэмульсии и микроэмульсии.

Segesteron aцетат (SA) является селективным и мощным агонистом рецептора прогестерона с потенциальным применением в лечении неврологических заболеваний, таких, как множественный склероз и инсульт. В этом исследовании микроэмульсия (МЭ) и three Наноэмульсии (NEs) с целевой концентрацией SA 0.48 Мг/г были разработаны для интраназального администрирования и подробно описаны в отношении их физико-химических свойств, устойчивости, антимикробной активности и безопасности (на первичных кортикальных клетках, тесте на яйцеклетки Hen/s, модели MucilAirTM и на крысах). Измерялись уровни плазмы и SA мозга

Identification of Novel Sphydrofuran-Derived Derivatives with Lipid-Lowering Activity from the Active Crude Extracts of Nocardiopsis sp. ZHD001.

Lipid-lowering is one of the most effective methods of prevention and treatment for cardiovascular diseases. However, most clinical lipid-lowering drugs have adverse effects and cannot achieve the desired efficacy in some complex hyperlipidemia patients, so it is of great significance to develop safe and effective novel lipid-lowering drugs. In the course of our project aimed at discovering the chemical novelty and bioactive natural products of marine-derived actinomycetes, we found that the organic crude extracts (OCEs) of Nocardiopsis sp. ZHD001 exhibited strong in vivo efficacies in reducin

Совпадение в полном тексте источника
… Next, we demonstrated that compounds 1 – 3 can inhibit the lipid droplet accumulation caused by fatty acid treatment in HepG2 cells at the concentration of 10 μM ( Figure 6 and Figure S20 ). … Lipid droplets were observed in an Oil Red O experiment. HepG2 was inoculated in 12-well culture plates with about 300,000 cells per well at 37 °C in a 5% CO 2 incubator for 24 h. …

Acoustically-Activated Liposomal Nanocarriers to Mitigate the Side Effects of Conventional Chemotherapy with a Focus on Emulsion-Liposomes.

To improve currently available cancer treatments, nanomaterials are employed as smart drug delivery vehicles that can be engineered to locally target cancer cells and respond to stimuli. Nanocarriers can entrap chemotherapeutic drugs and deliver them to the diseased site, reducing the side effects associated with the systemic administration of conventional anticancer drugs. Upon accumulation in the tumor cells, the nanocarriers need to be potentiated to release their therapeutic cargo. Stimulation can be through endogenous or exogenous modalities, such as temperature, electromagnetic irradiati