Endometriosis is a common gynecological disease in which lipid metabolic dysregulation has been increasingly implicated. However, the specific metabolic changes in ectopic lesions and stromal cells remain poorly understood. It is also unclear whether these changes contribute to lipid droplet accumulation or how this process is controlled at the transcriptional level. Here, we report that ectopic stromal cells exhibit broad lipid remodeling, showing changes in phosphatidylcholines, lysophosphatidylcholines, sphingomyelins, and acylcarnitines. Both ectopic lesions and ectopic stromal cells showed increased triacylglycerol and total cholesterol levels, lipid droplet accumulation, and reduced E2F1 expression. Integrated epigenomic and transcriptomic analyses of patient-derived ectopic stromal cells, together with mechanistic validation, revealed that E2F1 transcriptionally activates MGLL, which encodes monoacylglycerol lipase, a lipolytic enzyme involved in lipid mobilization. Both in vitro and in vivo experiments showed that downregulation of E2F1 increased lipid droplet accumulation, whereas restoring MGLL expression partially reversed this effect. Consistently, targeted lipidomic analysis of ectopic stromal cells following MGLL knockdown showed increased levels of several diacylglycerol species and alterations in sphingomyelin profiles. In summary, our findings suggest that E2F1 downregulation reduces MGLL expression and impairs lipid mobilization, which may contribute to lipid droplet accumulation and endometriotic lesion growth.

Type I interferon induces multiple protein effectors to inhibit viral replication. Among these, the interferon-induced transmembrane protein (IFITM3) and the cholesterol-25-hydroxylase (CH25h) converge on the inhibition of viral entry by altering the behavior of membranes. Here, we dissect the functional and mechanistic relationship between these two membrane-acting effectors using different viruses. When using HIV-1 and vesicular stomatitis virus (VSV), IFITM3 and CH25h restrict viral entry with similar efficiency but act in a largely redundant manner, a finding that is consistent across infection systems, cell types, and entry assays. However, this is not the case for several orthoflaviviruses against which IFITM3, but not CH25h, provides a strong block to infection. We further uncover that the CH25h-25HC axis remodels IFITM3 trafficking by driving partial relocalization of IFITM3 from endolysosomal compartments to the plasma membrane. This occurs by impairing IFITM3 internalization into early endosomes and leads to an increase in its secretion in exosomal vesicles, overall indicating that CH25h contributes to regulate IFITM3 cellular dynamics. Together, these findings reveal that the apparent redundancy of maintaining two distinct effectors targeting the same step of the viral life cycle is not superfluous but instead allows the cell to compensate and, nonetheless, target viruses that may have developed resistance to one of these effectors. Furthermore, the ability of CH25h to remodel IFITM3 trafficking indicates that these two pathways are connected, adding an additional layer of complexity in the biology of IFITM3.IMPORTANCEIFITM3 and CH25h are two potent, broad-acting inhibitors of viral membrane fusion, but their functional connections have not been explored. Here, we show that although their antiviral activities are largely redundant against HIV-1 and vesicular stomatitis virus (VSV), IFITM3 functionally compensates for a relative resistance of orthoflaviviruses toward CH25h. Furthermore, CH25h redistributes IFITM3 from endosomal compartments to the plasma membrane, enhancing its release in exosomal vesicles. Overall, these findings reveal that despite the fact that IFITM3 and CH25h can act redundantly against certain classes of viruses, IFITM3 can functionally compensate for CH25h resistance against other viruses, highlighting why it is important for the cell to maintain two distinct pathways to block virus-to-cell membrane fusion. In addition, these results also reveal how interferon-driven lipid remodeling can reshape the trafficking behavior of IFITM3, leading it to be more present in exosomes, where it could exert paracrine functions that remain to be explored.

Attention to exploring endothelial cell (EC) metabolism is increasing, but a holistic perspective on the metabolic adaptations of ECs during angiogenic proliferation is still missing. Here, we use a previously in-house developed computational EC-adapted genome-scale metabolic model that recapitulates known metabolic features in proliferating ECs to predict novel pathways central to biomass synthesis. We unveil the metabolic function of the glutamate-aspartate antiporter SLC25A13, previously overlooked in ECs, as a key regulator of glutamine utilization and provide evidence regarding its contribution to the generation of cholesterol and other biomass precursors. To our knowledge, predominant SLC25A13-linked utilization of glutamine for cholesterol synthesis has not been reported in other cell types in prior literature. Silencing of SLC25A13 in ECs reduced proliferation and vessel sprouting in vitro as well as in a choroidal neovascularization mouse model. These insights underscore the particular characteristics of EC metabolism and may warrant further evaluation of SLC25A13 as a putative new anti-angiogenic target.

Testosterone deficiency (TD) has been closely associated with systemic inflammation and metabolic disturbances. The C-reactive protein-albumin-lymphocyte (CALLY) index is a composite biomarker integrating inflammatory, nutritional, and immune parameters. However, its association with TD remains unclear. This study aimed to investigate the relationship between the CALLY index and TD in adult men.

ER+ (estrogen receptor positive) breast cancer is the most common subtype of breast cancer, for which endocrine therapy is the primary treatment. However, the development of drug resistance severely limits the clinical efficacy. In recent years, lipid metabolism reprogramming, as a key metabolic feature of tumor cells adapting to microenvironmental stress and driving progression and metastasis, has gained increasing attention due to its role in promoting endocrine therapy resistance. This review focuses on the lipid metabolism reprogramming that occurs in ER+ breast cancer cells in response to endocrine therapy, systematically elaborating on the key molecular mechanism changes in fatty acid synthesis, cholesterol metabolism, lipid droplet homeostasis, and mitochondrial fatty acid β-oxidation. These metabolic remodeling processes not only provide survival advantages and energy to drug-resistant cells but also directly promote the formation and development of drug-resistant phenotypes by affecting signal transduction and epigenetic regulation pathways. By integrating the latest research progress in this field, this article aims to deeply reveal the intrinsic connection between lipid metabolism reprogramming and endocrine resistance, providing important theoretical basis and direction for overcoming the bottleneck of drug resistance and developing new combination therapy strategies targeting lipid metabolism.

To reconnoitre the mechanism of Abietic acid (AA) in diabetes by in-silico and in-vivo experiments. Using GeneCards, diabetes gene targets were obtained. The protein-protein interaction and network topology analysis were performed using the String platform and Cytoscape 3.7.2. The enrichment analysis was done by Shiny GO. The docking was by Autodeck. Diabetes was induced by injecting STZ (55 mg/kg, i.p once) in Sprague-Dawley rats. The parameters included glucose, lipids, blood pressure, ECG, OGTT, kidney and cardiac markers, liver enzymes, AMPK, Nrf2, PPAR-γ, TLR-4, oxidative markers, LVF tests, and histopathology. AA interacts with 15 important targets (PIK3CD, MAPK1, NF-κB, mTOR, STAT3, GRIN1, ITGB3, ACACA, HSP90AB1, SERPINE1, ADRB1, ULK1, TLR4, CTSD, CDK5). The signalling pathways, like insulin, MAPK1, TLR, AMPK, JAK-STAT, are associated with these proteins. In docking, the highest affinity of AA was observed for ITGB3 (- 8.1), TLR4 (- 7.8), and ACACA (- 7.3). In rats, AA(40 and 80 mg/kg) decrease hyperglycaemia and hyperinsulinemia, improves glucose tolerance, normalize blood pressure, combat dyslipidaemia (decrease triglyceride, total cholesterol, LDL, increase HDL), preserves myocytes and ventricular function (decrease troponin-I, LDH, CK-MB, LVEDP, normal ECG), hepatoprotective (decrease AST, ALT), reno-protective (decrease creatinine, urea, uric acid) and combat oxidative stress (decrease MDA, increase SOD, catalase). Nrf2, AMPK, and PPAR γ levels were increased while TLR-4 levels were decreased after AA treatment. The study is supported by the preserved histopathological architecture of pancreatic, renal, hepatic, and cardiac cells. The present study preliminarily clarifies that AA exhibits therapeutic potential in preclinical models through multitargets and multi-pathways (Nrf/TLR4/PPAR γ), which points out a new direction for further research and clinical application.

Pyroptosis is a form of programmed cell inflammatory death. Macrophage pyroptosis has been implicated in the development of various immune diseases, yet its role in lupus nephritis (LN) remains poorly understood. This study examined macrophage pyroptosis in LN and its clinical correlations. This was a cross-sectional observational study. Renal tissues and clinical data were collected from 49 LN patients and 20 minimal change disease (MCD) patients. Macrophage pyroptosis was detected using immunofluorescence (cluster of differentiation 68 [CD68]/gasdermin D [GSDMD] co-staining), and serum inflammatory markers were analyzed via ELISA. Hierarchical regression analyses were performed to identify clinical parameters significantly associated with macrophage pyroptosis. A comparative analysis between the LN cohort (41 females, 8 males; mean age 32.6 ± 12.1 years) and MCD controls revealed significantly elevated levels of blood urea nitrogen, C-reactive protein, uric acid, and anti-double-stranded DNA antibodies (P < .05), accompanied by decreased complement component 3 (C3), complement component 4 (C4), estimated glomerular filtration rate (eGFR), and total cholesterol. Immunofluorescence demonstrated a marked increase in CD68/Cleaved GSDMD double-positive cells within both glomerular and interstitial compartments of LN patients (P < .001). LN patients with chronic kidney disease (CKD) stages 5 exhibited significantly interstitial macrophage pyroptosis (P < .05). This study is the first to report the presence of macrophage pyroptosis in LN renal tissues, with the extent of interstitial pyroptosis showing a significant cross-sectional association with CKD stage (by eGFR). This observation suggests a potential link between macrophage pyroptosis and disease severity in LN, meriting further investigation.

Type 2 diabetes mellitus (T2DM) is a major risk factor for atherosclerotic cardiovascular disease (CVD), and hyperlipidemia (HLD) frequently coexists. Shear wave elastography (SWE) quantifies carotid stiffness and may improve CVD risk stratification. To evaluate the impact of HLD on carotid stiffness in T2DM using SWE. We conducted a cross-sectional study of 112 adults with T2DM: simple diabetes (Group B, n = 52) and T2DM with HLD (Group C, n = 60): and 55 healthy controls (Group A). Demographic, clinical, and biochemical data were collected. Conventional ultrasound measured carotid intima-media thickness, diastolic diameter, systolic diameter, and peak systolic velocity. Arterial distensibility and the stiffness coefficient were calculated. SWE provided maximum, mean, and minimum elastic moduli. Pearson correlation tested associations between SWE parameters and risk factors; multivariable linear regression identified independent determinants of SWE values. Compared with controls, Groups B and C had higher fasting glucose, glycated hemoglobin, total cholesterol (TC), triglycerides (TG), and LDL-C (all P < .05); TC, TG, and LDL-C were higher in Group C than Group B (all P < .05). high-density lipoprotein cholesterol (HDL-C) were lower in both Group B and Group C compared to Group A (both P < .05), and were also lower in Group C than in Group B (P < .05). Mean elastic modulus, maximum elastic modulus, and minimum elastic modulus were greater in Groups B and C than in controls and were highest in Group C (all P < .05). SWE parameters correlated positively with carotid intima-media thickness, TC, TG, and LDL-C, and negatively correlated with HDL-C (all P < .05). In multivariable models, hyperlipidemia: driven primarily by elevated TC, TG, and LDL-C and reduced HDL-C: was independently associated with increased SWE values in T2DM (all P < .05). HLD exacerbates carotid atherosclerosis in T2DM. SWE is a noninvasive, quantitative, and efficient method for assessing carotid stiffness and cardiovascular risk in T2DM, particularly among patients with concurrent HLD.

Obstructive sleep apnea (OSA) is linked to fasting plasma glucose, high-density lipoprotein cholesterol, and body mass index. However, the association between OSA and the ln[(fasting plasma glucose)/(high-density lipoprotein cholesterol)] × body mass index (FHB) index: calculated as ln(FPG/HDL-C) × BMI: has not been extensively investigated in US adults. This research aims to investigate whether the FHB index is associated with the risk of self-reported OSA symptoms among US adults. The analysis utilized National Health and Nutrition Examination Survey datasets collected during the 2005 to 2008 and 2015 to 2018 survey cycles. Weighted multivariable regression and curve fitting were applied to explore the FHB index-OSA correlation, while subgroup and sensitivity analyses were conducted to evaluate the consistency of this relationship. Among 7414 study subjects, 3694 reported symptoms of OSA. Curve fitting showed a nonlinear positive relationship of the FHB index for OSA risk (P for nonlinearity <.001), with an identified threshold of 25.84. Below this value, each 1-unit increase in the FHB index was linked to a 5.2% increase in OSA risk (odds ratio [OR] = 1.052; 95% confidence interval [CI]: 1.009-1.096). Above this value, each 1-unit increase was linked to a 2.6% increase (OR = 1.026; 95% CI: 1.022-1.031). When the FHB index was analyzed as a categorical variable, individuals in the third tertile of the FHB index had odds of OSA that were 211.9% higher than those in the first tertile (OR = 3.119; 95% CI: 2.675-3.635). Subgroup and sensitivity analyses confirmed the robustness of this association. This cross-sectional study revealed a nonlinear positive relationship between the FHB index and self-reported OSA among US adults. The FHB index may serve as a novel and convenient candidate marker for identifying individuals at high-risk of OSA, meriting further investigation. However, before considering clinical application, these findings require validation through longitudinal studies.

Ischemic heart disease (IHD) remains a leading global health burden influenced by demographic transitions, socioeconomic disparities, and modifiable risk factors. Comprehensive analyses of global patterns are crucial to inform public health interventions. Using data from the Global Burden of Disease study 2021, we assessed global, regional, and national trends in IHD burden (1990-2021). Age-standardized rates of incidence, prevalence, mortality, and disability-adjusted life-years were evaluated. Trends were analyzed using estimated annual percentage change, age-period-cohort models, Bayesian forecasts, risk-factor attribution, decomposition analyses, health inequality, and frontier efficiency analyses. From 1990 to 2021, global IHD prevalence nearly doubled despite stable age-standardized rates, driven by population aging and growth. Eastern Europe exhibited consistently high disease burdens compared to sub-Saharan Africa. Significant gender disparities persisted, with higher burdens among males. High blood pressure, low-density lipoprotein cholesterol, and dietary risks dominated globally. Although age-standardized incidence and mortality declined, especially in high-sociodemographic index countries, absolute numbers increased due to demographic momentum. Forecasts suggest continued increases in absolute cases and deaths through 2035 despite declining standardized rates.Despite reductions in age-standardized IHD burden, substantial disparities persist. Future strategies should address demographic drivers, expand preventive efforts in lower-sociodemographic index regions, and enhance health system efficiency.

Coronary artery disease (CAD) remains a major cause of morbidity and mortality worldwide. Although guideline-directed Western medical therapy improves cardiovascular outcomes, residual symptoms remain common. Integrated traditional Chinese and Western medicine is frequently used as an adjunctive strategy in China, but its real-world, short-term clinical associations require further characterization. This retrospective observational study included 215 patients with CAD treated between January 2022 and December 2024, including 106 patients receiving conventional Western medical therapy alone and 109 receiving adjunctive traditional Chinese medicine based on syndrome differentiation. Symptom status, laboratory parameters, overall clinical response, and documented adverse events were compared between groups. Because treatment allocation was nonrandom and the analyses were unadjusted for potential confounders, all between-group findings were interpreted as associations. No statistically significant differences were observed in the measured baseline demographic, clinical, or laboratory characteristics between the 2 groups. After treatment, the integrated-treatment group had lower rates of residual chest pain, chest tightness, and fatigue and greater changes in total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fibrinogen, and D-dimer. The observed overall clinical response rate was higher in the integrated-treatment group (90.8% vs 76.4%, P = .004). Documented adverse-event incidence did not differ significantly between groups. In this retrospective real-world cohort, adjunctive traditional Chinese medicine was associated with greater short-term improvement in selected symptoms and laboratory parameters and a higher observed clinical response rate, without a detectable increase in documented short-term adverse events. These unadjusted observational findings are exploratory, do not establish causal superiority or improved cardiovascular prognosis, and are insufficient by themselves to modify current guideline-directed CAD practice.