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Involvement of ACACA (acetyl-CoA carboxylase α) in the lung pre-metastatic niche formation in breast cancer by senescence phenotypic conversion in fibroblasts.

BACKGROUND: Reprogramming of metabolism is strongly associated with the development of cancer. However, the role of metabolic reprogramming in the remodeling of pre-metastatic niche (PMN), a key step in metastasis, is still unknown. We aimed to investigate the metabolic alternation during lung PMN formation in breast cancer. METHODS: We assessed the transcriptomes and lipidomics of lung of MMTV-PyVT mice by microarray and liquid chromatography-tandem mass mass spectrometry before lung metastasis. The validation of gene or protein expressions was performed by quantitative real-time polymerase …

Multi-omics analysis reveals attenuation of cellular stress by empagliflozin in high glucose-treated human cardiomyocytes.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors constitute the gold standard treatment for type 2 diabetes mellitus (T2DM). Am … y the metabolic effect of EMPA on the human myocardial cell model by using orthogonal metabolomics, lipidomics, and proteomics approaches. The untargeted and multivariate analysis mimicked the fasting blood sugar level of T2DM patients (hyperglycemia: HG) and in the average blood sugar range (normal glucose: NG), with and without the addition of EMPA. RESUL …

Function and regulation of a steroidogenic CYP450 enzyme in the mitochondrion of Toxoplasma gondii.

As an obligate intracellular parasite, Toxoplasma gondii must import essential nutrients from the host cell into the parasitophorous vacuole … such as members of the membrane-associated progesterone receptor (MAPR) family. Our LC-MS targeted lipidomics detect selective classes of hormone steroids in Toxoplasma, with a predominance for anti-inflammatory hydroxypregnenolone species, deoxycorticosterone and dehydroepiandrosterone. The genome of Toxoplasma contains homologs encoding a single type I CY …

Immune and metabolic markers for identifying and investigating severe Coronavirus disease and Sepsis in children and young people (pSeP/COVID ChYP study): protocol for a prospective cohort study.

INTRODUCTION: Early recognition and appropriate management of paediatric sepsis are known to improve outcomes. A previous system's biology i … ensive care and with an acute illness to follow time dependent changes in biomarkers. An integrated lipidomics and RNASeq transcriptomics analyses will be conducted to evaluate immune-metabolic networks that discriminate sepsis and COVID-19 from other acute illnesses. This study received approval for deferred consent. ETHICS AND DISSEMINATION: The study has …

Juvenile CLN3 disease is a lysosomal cholesterol storage disorder: similarities with Niemann-Pick type C disease.

BACKGROUND: The most common form of neuronal ceroid lipofuscinosis (NCL) is juvenile CLN3 disease (JNCL), a currently incurable neurodegener … thus providing a positive control. The lipid and protein content of LE/Lys was then analysed using lipidomics and proteomics, respectively. FINDINGS: Lipid and protein profiles of LE/Lys isolated from JNCL patients were profoundly altered compared to controls. Importantly, cholesterol accumulated in LE/Lys of JNCL samples to a comparable extent than in NPC …

Устная инфекция, оральная патология и слюнная диагностика заболевания Mpox: актуальность с точки зрения дантиста и OMICs.

В этом описательном обзоре мы стремимся указать на тесную связь между инфекцией вируса mpox (MPXV) и ролью слюны в качестве диагностического инструмента для борьбы с этим вирусом с учетом нынешнего молекулярного подхода и перспективы применения ОМИК. MPXV использует грубый эндоплазмический ретикулум, рифозомы и цитоплазмические белки, чтобы воспроизвести свой геном и синтезировать вирионы для выхода из клетки. Одним из первых признаков инфекции является наличие пероральных слизей, связанных с инфекцией мпокса; однако нынешние диагностические средства не позволяют обнаружить вирус до начала сып

Совпадение в аннотации оригинала
In this narrative review, we aim to point out the close relationship between mpox virus (MPXV) infection and the role of saliva as a diagnos … with a sensitivity of 85%-100%. In this context, the application of transcriptomics, metabolomics, lipidomics, or proteomics analyses coupled with saliva can identify novel disease biomarkers. Thus, it is important to note that the identification and quantification of salivary DNA, RNA, lipid, protein, and metabolite can provide novel non-invasive biomarker …

Transcriptional Integration of Distinct Microbial and Nutritional Signals by the Small Intestinal Epithelium.

BACKGROUND & AIMS: The intestine constantly interprets and adapts to complex combinations of dietary and microbial stimuli. However, the tra … ngle high-fat meal. Preparations of unsorted jejunal intestinal epithelial cells were queried using lipidomics and genome-wide assays for RNA sequencing and ChIP sequencing for the activating histone mark H3K27ac and hepatocyte nuclear factor 4 alpha. RESULTS: Analysis of lipid classes, genes, and regulatory regions identified distinct nutritional and micro …

A human liver chimeric mouse model for non-alcoholic fatty liver disease.

BACKGROUND & AIMS: The accumulation of neutral lipids within hepatocytes underlies non-alcoholic fatty liver disease (NAFLD), which affects … eveloped pronounced steatosis whereas murine hepatocytes remained normal. Unbiased metabolomics and lipidomics revealed signatures of clinical NAFLD. Transcriptomic analyses showed that molecular responses diverged sharply between murine and human hepatocytes, demonstrating stark species differences in liver function. Regulatory network analysis indicated cl …

Saroglitazar and Hepano treatment offers protection against high fat high fructose diet induced obesity, insulin resistance and steatosis by modulating various class of hepatic and circulating lipids.

Higher global prevalence of non-alcoholic fatty liver disease (NAFLD) is associated with obesity, steatosis, and insulin resistance (IR), an … d hepatic lipid accumulation. Differential liquid chromatography-mass spectrometry (LC-MS/MS) based lipidomics analysis demonstrated significant changes in the different class of lipids [phospholipids, sphingolipids, diglycerides and triglycerides (TG)] in HFHF fed group. The protective effects of both Saroglitazar and Hepano were evident against IR, obesity …

Safety and Preliminary Efficacy of a Novel Host-Modulatory Therapy for Reducing Gingival Inflammation.

BACKGROUND: Periodontal disease is among the sixth most common inflammatory diseases worldwide with high risk to promote complications from … ammation and periodontal pocket depth (PD). Serum SPMs were monitored using targeted lipid mediator lipidomics to assess potential systemic impact of BLXA4. RESULTS: The frequency of TEAEs was similar in BLXA4 and placebo-treated groups with no study-related SAEs. Once-daily rinsing with BLXA4 for 28-days resulted in a greater decrease in gingival inflammat …

Effects of Dicyclohexyl Phthalate Exposure on PXR Activation and Lipid Homeostasis in Mice.

BACKGROUND: Exposure to plastic-associated endocrine disrupting chemicals (EDCs) has been associated with an increased risk of cardiovascula … the impact of DCHP exposure on PXR activation and lipid homeostasis in vitro and in vivo. Targeted lipidomics were performed to measure circulating ceramides, novel predictors for CVD. RESULTS: DCHP was identified as a potent PXR-selective agonist that led to higher plasma cholesterol levels in wild-type mice. DCHP was then demonstrated to activate intesti …

An Interferon Regulated MicroRNA Provides Broad Cell-Intrinsic Antiviral Immunity through Multihit Host-Directed Targeting of the Sterol Pathway.

In invertebrates, small interfering RNAs are at the vanguard of cell-autonomous antiviral immunity. In contrast, antiviral mechanisms initia … , post-transcriptionally via miR-33, and enzymatically via IDI1 and SC4MOL. Mass spectrometry-based lipidomics and enzymatic assays demonstrate the targeting mechanisms reduce intermediate sterol pathway metabolites and total cholesterol in macrophages. These results reveal a previously unrecognized mechanism by which IFN regulates the sterol pathway. The st …

Selective activation of the prostaglandin E2 circuit in chronic injury-induced pathologic angiogenesis.

PURPOSE: Cyclooxygenase (COX)-derived prostaglandin E(2) (PGE(2)) is a prevalent and established mediator of inflammation and pain in numero … neovascularization quantified by CD31/PECAM-1 immunofluorescence. PGE(2) formation was analyzed by lipidomics and polymorphonuclear leukocyte (PMN) infiltration quantified by myeloperoxidase activity. Expression of EPs and inflammatory/angiogenic mediators was assessed by real-time PCR and immunohistochemistry. Mice eyes were treated with PGE(2) (100 ng top …

The dark septate endophyte S16 enhances drought tolerance in sweet cherry by coordinating metabolic reprogramming and the transcription factor PaHB12.

Drought severely limits the growth and productivity of sweet cherry (Prunus avium L.), a fruit crop highly sensitive to water deficit. Beneficial root-associated fungi, particularly dark septate endophytes (DSEs), have emerged as potential modulators of stress tolerance, yet their underlying mechanisms in perennial fruit trees remain poorly understood. In this study, we investigated the effects of the DSE fungus Helotiales sp. S16 on drought responses of sweet cherry rootstock Gisela 5 seedlings. Fungal symbiosis was established by homogenizing fungal suspension with sterile growth substrate,

Sex-Specific Associations Between Per- and Polyfluoroalkyl Substances and the Risk of Type 2 Diabetes: The Role of Genetic Susceptibility and Lipid Metabolism.

To elucidate the sex-specific associations of per- and polyfluoroalkyl substances (PFASs) on type 2 diabetes (T2D) risk and to explore whether genetic susceptibility and baseline lipid profiles may help explain these associations. A nested case-control study including 985 matched case-control pairs from the Dongfeng-Tongji Cohort was conducted. Serum PFAS concentrations, T2D-related pathway polygenic risk scores (PRSs), blood lipid profiles, and plasma lipidomes were integrated. Conditional logistic regression, weighted quantile sum (WQS) regression, mediation analysis, and gene-environment in

An age-preserving neuronal iSpheroid platform for modeling human aging and Alzheimer's disease.

UNLABELLED: Aging is the strongest risk factor for Alzheimer's disease (AD), yet existing human neuronal models either erase age-associated features during reprogramming or fail to recapitulate three-dimensional organization of human neuronal tissue. Here, we establish directly induced neuronal spheroids (iSpheroids), a scalable three-dimensional platform generated by direct conversion of primary fibroblasts without pluripotency. iSpheroids generate long-lived, electrophysiologically active neurons from young, unimpaired aged, and sporadic AD donors while preserving donor-specific epigenetic a

Aberrant erythrocyte rigidity in JAK2V617F myeloproliferative neoplasms underlies concurrent thrombosis and hemorrhage.

Thrombotic events are the leading cause of death in myeloproliferative neoplasms (MPNs) driven by the JAK2 Val617→Phe (JAK2V617F) mutation. We investigated how JAK2V617F alters hemostasis and thrombosis in humans and in lineage-specific knockin mice to test whether red blood cell (RBC) mechanics contribute directly to clot pathology. Jak2F/+Vav-Cre knockin mice form structurally aberrant clots characterized by extended clot formation times and unstable hemostatic plug formation. Whole-blood clot contraction in vitro was impaired in humans and mice carrying the JAK2V617F mutation, even when Jak

Fatty acid esters of hydroxy fatty acids and alkyl-diacylglycerols: minor but bioactive components in human milk.

As the optimal source of nutrition for infants, investigations into the human milk lipidome have been quite extensive. Much of the work, however, has been focused on major lipid components such as triglycerides, possibly undermining its actual complexity. This review focuses on two minor but bioactive lipid classes in human milk: fatty acid esters of hydroxy fatty acids (FAHFAs) and alkyl-diacylglycerols (TG(O)s). FAHFAs are known to exhibit anti-diabetic and anti-inflammatory effects, while TG(O)s are important for the prevention of childhood obesity. With the knowledge that early nutrition a

PNPLA3-I148M reduces hepatic triacylglycerol secretion and mitigates diet induced left ventricular diastolic dysfunction.

PNPLA3-I148M, the greatest genetic determinant for metabolic dysfunction-associated steatotic liver disease (MASLD), paradoxically associates with reduced cardiovascular disease (CVD); however, the mechanisms are poorly understood. To investigate how PNPLA3-I148M alters hepatic triacylglycerol (TAG) metabolism and influences cardiac function, we expressed human WT-PNPLA3, PNPLA3-I148M, or GFP in the liver of PNPLA3-/- mice and fed them chow or Metabolic Dysfunction-Associated Steatohepatitis (MASH) diet at thermoneutrality. After 4 weeks of MASH diet, PNPLA3‑I148M mice showed reduced hepatic T

Exercise attenuates atherosclerosis by inhibiting eWAT aging via targeting SIRT1/pyruvate carboxylase pathway.

Aging is the primary risk factor for atherosclerosis (AS). Epididymal white adipose tissue (eWAT) is a key driver of organismal aging and age-related diseases. Exercise is known to protect against AS, but the role of aging eWAT in this process remains unclear. To this end, we investigated whether exercise inhibits AS by regulating aging eWAT and elucidated the involved mechanisms. ApoE-/- and C57BL/6 mice were fed a high-fat diet (HFD) to mimic poor lifestyle habits and explore eWAT senescence evolution. We found eWAT is a senescence-susceptible organ, exhibiting time-dependent deterioration u