Distinct Lipid Research Articles

Synergistically Activated Aggregation-Induced Emission Probe for Precise In Situ Staining of Lipids in Atherosclerotic Plaques.

Visualizing the localization and distribution of lipids within arteries is crucial for studying atherosclerosis. However, existing lipid-specific probes face challenges such as strong hydrophobicity and nonspecific staining of lipophilic organelles or tissues, making them impractical for the precise identification of atherosclerotic plaques. To address this issue, we design a synergistically activated probe, Cbz-Lys-Lys-TPEB, which responds to cathepsin B (CTB) and H2O2 for the in situ generation of aggregation-induced emission luminogens (AIEgens). This enables specific staining of lipids within arteries and precise imaging of atherosclerotic plaques. The probe combines a tetraphenylethene building block with a hydrophilic peptide sequence (Cbz-Lys-Lys) and phenylboric acid module, providing excellent water solubility and fluorescence quenching in a molecular dispersion state. Upon interaction with H2O2 and CTB within plaques, the hydrophilic Cbz-Lys-Lys-TPEB probe is specifically cleaved and converted into hydrophobic AIEgens, leading to rapid aggregation and significant fluorescence enhancement. Interestingly, the in situ-liberated AIEgens display distinct lipid binding ability, effectively tracking the location and distribution of lipids in plaques. This synergistic target-activated AIEgen liberation strategy demonstrates significant feasibility for the reliable and accurate identification of atherosclerotic plaques, holding tremendous potential for clinical diagnosis and risk stratification of atherosclerosis.

Exploring the roles of Lem2 and Bqt4 in lipid metabolism for nuclear envelope maintenance: a novel perspective

Abstract The nuclear envelope (NE) is a double-membrane structure critical for genome maintenance and cellular function, composed of the inner and outer nuclear membranes. In fission yeast, the inner nuclear membrane (INM) proteins Lem2 and Bqt4 are essential for maintaining NE integrity. The study published by Hiraoka group explores the interactions between Lem2 and Bqt4 with lipid synthesis enzymes, addressing their roles in NE maintenance. The authors identified Lem2- and Bqt4-binding proteins using immunoprecipitation and mass spectrometry, revealing that Lem2 interacts with lipid synthesis enzymes, whilst Bqt4 binds to an enzyme that involves in glucosylceramide synthesis. These findings suggest that Lem2 and Bqt4 independently contribute to NE structure and its integrity through distinct lipid metabolic pathways, highlighting their complementary roles in nuclear membrane homeostasis. This study represents a significant step forward in the field of NE biology to unravel the complexities of nuclear membrane dynamics.

Nanoparticle-Directed Antioxidant Therapy Can Ameliorate Disease Progression in a Novel, Diet-Inducible Model of Coronary Artery Disease.

Oxidative stress plays a crucial role in the pathogenesis of coronary artery disease. In cardiovascular research using murine models, the generation and maintenance of models with robust coronary arterial atherosclerosis has been challenging. We characterized a new mouse model in which the last 3 amino acids of the carboxyl terminus of the HDL (high-density lipoprotein) receptor (SR-B1 [scavenger receptor class B, member 1]) were deleted in a low-density lipoprotein receptor knockout (LDLR-/-) mouse model (SR-B1ΔCT/LDLR-/-) fed an atherogenic diet. We also tested the therapeutic effects of an oxidative stress-targeted nanoparticle in atherogenic diet-fed SR-B1ΔCT/LDLR-/- mice. The SR-B1ΔCT/LDLR-/- mice fed an atherogenic diet had occlusive coronary artery atherosclerosis, impaired cardiac function, and a dramatically lower survival rate, compared with LDLR-/- mice fed the same diet. As SR-B1ΔCT/LDLR-/- mice do not exhibit female infertility or low pup yield, they are far easier and less costly to use than the previously described SR-B1-based models of coronary artery disease. We found that treatment with the targeted nanoparticles improved the cardiac functions and corrected hematologic abnormalities caused by the atherogenic diet in SR-B1ΔCT/LDLR-/- mice but did not alter the distinctive plasma lipid levels. The SR-B1ΔCT/LDLR-/- mice developed diet-inducible, fatal atherosclerotic coronary artery disease, which could be ameliorated by targeted nanoparticle therapy. Our study provides new tools for the development of cardiovascular therapies.

Wavelet‐Forward Family Enabling Stitching‐Free Full‐Field Fourier Ptychographic Microscopy

AbstractFourier ptychographic microscopy (FPM) breaks through the resolution limitations of conventional optical systems, which offer a full‐field view and high resolution without additional mechanical scanning. However, conventional image‐domain optimizations require trade‐offs between correction efficacy, data redundancy, and reconstruction accuracy. Furthermore, the existing linear time‐invariant model for actual nonlinear, time‐varying optical systems leads to forward model mismatch, complicating the corrections of the vignetting effect. To overcome these challenges and achieve stitching‐free FPM, a family of forward wavelet‐transform models (WL‐FPM) is proposed. WL‐FPM employs the reversibility of the wavelet transform for high‐fidelity reconstruction in the multiscale feature domain. The wavelet loss function is updated in each iteration, and non‐convex optimization is solved by complex back diffraction. WL‐FPM offers stitching‐free, high‐resolution, and robust reconstruction under various challenging conditions, including vignetting effects, LED position mismatch, intensity fluctuations, and high‐level noise environments, which outperform conventional FPM methods. Under a 4X objective with NA 0.1, WL‐FPM achieves a 435‐nm resolution and stitching‐free full‐field reconstruction of a 3.328 × 3.328 mm2 pathological section with distinct subcellular organelles. In live cell imaging, it provides a full‐field observation with distinct lipids in a single cell. A large number of simulation and experimental results demonstrate its potential for biomedical applications.

Lipidomic profiling of triple-negative breast cancer cells reveals distinct metabolic signatures associated with EpCAM expression

Lipid metabolism is essential at all stages of cancer progression, particularly for triple-negative breast cancer (TNBC) the deadliest cancer subtype for women patients. TNBC cells exhibit significant metabolic heterogeneity, which contributes to their aggressive behavior. Epithelial-to-mesenchymal transition (EMT), a key step in metastasis, is associated with distinct lipid profiles, where the epithelial cell adhesion molecule (EpCAM) was found to be decreased along the transition. To understand this link, we employed lipidomic profiling of the TNBC cell line SUM149PT, which exhibits high variability in EpCAM, an epithelial marker. Using EpCAM levels to categorize cells with high and low EpCAM expression using fluorescence-activated cell sorter, we performed targeted mass spectrometry analysis of various lipid classes (glycerophospholipids, glycerolipids, lysophospholipids, and sphingolipids) by a hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS)-based screening method. After correcting for cell size, we identified a unique lipid profile associated with each EpCAM expression level. Notably, cells with higher EpCAM expression displayed lower levels of lysophosphatidylethanolamine (LPE). This finding suggests a potential role for LPE in the regulation of EMT in TNBC.

Effects of different processing methods on the lipid composition of seabuckthorn fruit oil based on lipidomics.

Employing lipidomics, this study investigated the lipid composition of seabuckthorn fruit oil processed via supercritical CO2 extraction and centrifugal separation. Qualitative analysis showed that a total of 2861 lipid molecules were identified in seabuckthorn fruit oil. Quantitative analysis showed that the content of lipids in seabuckthorn fruit oil extracted by supercritical CO2 extraction (927,539.84µg/mL) was significantly higher than that in centrifugal-separated seabuckthorn fruit oil (735,717.63µg/mL), with 17 distinct lipid classes and 215 lipid molecules differentiated through multivariate statistical analysis. Lipid molecules, such as diacylglycerol (DG), ceramides (Cer), monohexosyl ceramide, phosphatidylglycerol, phosphatidylinositol, phosphatidylethanolamine, and monogalactosyl DG, were predominantly found in the oil extracted using supercritical CO2. In contrast, monogalactosyl monoacylglycerol, diglycosyl ceramide, and Cer phosphate were significantly present in the oil extracted by centrifugal separation. These findings contribute new insights into how processing methods affect the quality and composition of seabuckthorn fruit oil and provide a basis for detecting oil adulteration.

Sex-Specific Lipid Profiles and Flavor Volatiles in Giant Salamander (Andrias davidianus) Tails Revealed by Lipidomics and GC-IMS

To elucidate the relationships between lipid components and odor traits, this study comparatively characterized the distinct lipid compositions and flavor volatiles in giant salamander tails of different sexes via mass-spectrometry-based lipidomics and GC-IMS. A total of 3145 fat metabolites were detected in male and female giant salamander tails, with the largest contributors being triglycerides (TGs, 840) and phosphatidylcholines (PCs, 383). Notably, the contents of PCs and TGs were greater in female tails than in male tails, and the levels of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) were also greater in the female group. Additionally, a total of 45 volatile components were detected, namely, 14 aldehydes, 14 alcohols, 9 ketones, 3 acids, 3 esters, 1 ether, and 1 amine. Alcohols (29.96% to 34.85%) and aldehydes (21.07% to 22.75%) were the predominant volatiles. Multivariate statistical analysis revealed 22 key differential fats and 26 differential odor substances as distinguishing labels between sexes. Correlation analysis revealed that the concentrations of triethylamine, dimethyl sulfide, ethanol-D, and 3-methyl butanal-D were significantly positively correlated with the concentrations of diglyceride (DG) (26:6e), cardiolipin (CL) (59:4), acylcarnitine (AcCa) (22:4), and triglyceride (TG) (52:10) (p < 0.01). Threefold cross-validation revealed that the prediction accuracies of these differential lipids and volatile compounds for sex recognition via the random forest model were 100%. These findings might not only provide insight into the effects of sexes on the lipid and volatile profiles of giant salamander tails but also provide clues for their gender recognition.

Rheological and Lipid Characterization of Minipig and Human Skin Tissue: A Comparative Study Across Different Locations and Depths.

Understanding the rheology of minipig and human skin is crucial for enhancing drug delivery methods, particularly for injections. Despite many studies on skin's viscoelasticity, especially the subcutaneous layer, comparative analyses across different clinical sites are scarce, as is data on the impact of hydration or lipid levels. This study employs shear rheology and lipid analysis to evaluate viscoelasticity and lipid content across three anatomical locations-breast, belly, and neck and three different depth layers in Yucatan minipigs. It reports on how viscoelastic properties change with frequency, time, and strain, noting strain-stiffening and shear-thinning at high strain amplitudes. Human male and female abdominal tissues are also compared to minipig tissues, highlighting distinct viscoelastic traits and lipid's role in them. The findings suggest the existence of species, anatomical location, tissue depth, and sex-based rheological differences.Furthermore, the use of male minipig models for studying human male subcutaneous tissue is discussed.

Programming Bordetella pertussis lipid A to promote adjuvanticity

BackgroundBordetella pertussis is the causative agent of whooping cough or pertussis. Although both acellular (aP) and whole-cell pertussis (wP) vaccines protect against disease, the wP vaccine, which is highly reactogenic, is better at preventing colonization and transmission. Reactogenicity is mainly attributed to the lipid A moiety of B. pertussis lipooligosaccharide (LOS). Within LOS, lipid A acts as a hydrophobic anchor, engaging with TLR4-MD2 on host immune cells to initiate both MyD88-dependent and TRIF-dependent pathways, thereby influencing adaptive immune responses. Lipid A variants, such as monophosphoryl lipid A (MPLA) can also act as adjuvants. Adjuvants may overcome the shortcomings of aP vaccines.ResultsThis work used lipid A modifying enzymes from other bacteria to produce an MPLA-like adjuvant strain in B. pertussis. We created B. pertussis strains with distinct lipid A modifications, which were validated using MALDI-TOF. We engineered a hexa-acylated monophosphorylated lipid A that markedly decreased human TLR4 activation and activated the TRIF pathway. The modified lipooligosaccharide (LOS) promoted IRF3 phosphorylation and type I interferon production, similar to MPLA responses. We generated three other variants with increased adjuvanticity properties and reduced endotoxicity. Pyrogenicity studies using the Monocyte Activation Test (MAT) revealed that these four lipid A variants significantly decreased the IL-6, a marker for fever, response in peripheral blood mononuclear cells (PBMCs).ConclusionThese findings pave the way for developing wP vaccines that are possibly less reactogenic and designing adaptable adjuvants for current vaccine formulations, advancing more effective immunization strategies against pertussis.

How Bacteria Establish and Maintain Outer Membrane Lipid Asymmetry.

Gram-negative bacteria build an asymmetric outer membrane (OM), with lipopolysaccharides (LPS) and phospholipids (PLs) occupying the outer and inner leaflets, respectively. This distinct lipid arrangement is widely conserved within the Bacteria domain and confers strong protection against physical and chemical insults. The OM is physically separated from the inner membrane and the cytoplasm, where most cellular resources are located; therefore, the cell faces unique challenges in the assembly and maintenance of this asymmetric bilayer. Here, we present a framework for how gram-negative bacteria initially establish and continuously maintain OM lipid asymmetry, discussing the state-of-the-art knowledge of specialized lipid transport machines that place LPS and PLs directly into their corresponding leaflets in the OM, prevent excess PL accumulation and mislocalization, and correct any lipid asymmetry defects. We critically assess current studies, or the lack thereof, and highlight important future directions for research on OM lipid transport, homeostasis, and asymmetry.

Distinct plasma lipids predict axonal injury and multiple sclerosis activity

BackgroundLipids are of particular interest for the study of neuroinjury and neuroinflammation as structural lipids are major components of myelin, and a variety of lipid species modulate inflammation. In this...

Benzo[a]pyrene exposure induces anxiety-like behaviors in the mice through brain metabolic alterations

The deleterious health impacts of polycyclic aromatic hydrocarbons (PAHs) on the population have been extensively substantiated and acknowledged. Mounting evidence underscores that PAH exposure is closely linked to an elevated risk of mental disorders, particularly in populations experiencing occupational and high-level exposure. In this study, we aimed to investigate the mechanisms underlying anxiety-like behaviors induced by different dosages of PAHs, with a concentrated focus on brain region-specific metabolic alterations in mice using various metabolomics approaches. Male C57BL/6 mice were exposed to benzo[a]pyrene (B[a]P), a typical PAH, through gavage at occupational exposure and EPA toxicologically relevant dosages (2.0 and 20.0 mg/kg/day) for 21 days, respectively. Behavioral assessments revealed that occupational exposure to B[a]P induced anxiety-like behaviors in C57BL/6 mice. Meanwhile, elevated serum norepinephrine and corticotropin-releasing hormone further confirmed the anxiety-inducing effects of B[a]P exposure. Metabolomics analysis uncovered dysregulation across various metabolic pathways following B[a]P exposure, encompassing brain neurotransmitter, organic acid, amino acid, lipid, fatty acid, and cholesterol. Anxiety levels and lipid metabolic abnormalities were notably exacerbated at the higher dosage, despite being only a 10-fold increase. Of particular significance, a decrease in lysophosphatidic acid (LPA) and lysophosphatidylserine (LPS) emerged as pivotal indicators of B[a]P neurotoxicity. Spatial-resolved metabolomics further demonstrated distinctive lipid and metabolite profiles across different brain subregions after exposure to B[a]P. Remarkably, alterations were specifically observed in the anxiety-related brain regions, such as the hippocampus, cortex, white matter, and thalamus, varying with exposure dosages. These findings underscore the significance of brain metabolic abnormalities in the development of mental disorders triggered by B[a]P exposure and highlight the need for establishing precise exposure limits of B[a]P to safeguard public mental health.

Modulation of Annexin-Induced Membrane Curvature by Cholesterol and the Anionic Lipid Headgroup during Plasma Membrane Repair.

Annexins (ANXAs), calcium-sensitive phospholipid-binding proteins, are pivotal for cellular membrane repair, which is crucial for eukaryotic cell survival under membrane stress. With their unique trimeric arrangements and crystalline arrays on the membrane surface, ANXA4 and ANXA5 induce membrane curvature and rapidly orchestrate plasma membrane resealing. However, the influence of cholesterol and anionic lipid headgroups on annexin-induced membrane curvature remains poorly understood at the molecular level. Using all-atom molecular dynamics simulations, we measured the local curvature-induced underneath ANXA4 and ANXA5 monomers and trimers when they bind to lipid bilayers of distinct lipid compositions: PSPC (20% POPS, 80% POPC), PAPC (20% POPA, 80% POPC), and PSPCCHL (14% POPS, 56% POPC, 30% cholesterol). Laser injury experiments were conducted on MCF7 cells transfected to transiently express fluorescently labeled ANXA4 or ANXA5 to facilitate the examination of protein and lipid accumulation at the damage site. Annexin trimers induce higher curvature than monomers, particularly with cholesterol present. Annexin trimers induce similar curvatures on both PAPC and PSPC membranes. Notably, among monomers, ANXA5 induces the highest curvature on PAPC, suggesting more efficient recruitment of ANXA5 compared with ANXA4 in the early stages of membrane repair near a lesion. Laser injury experiments confirm rapid coaccumulation of phosphatidic acid lipids with ANXA4 and ANXA5 at repair sites, potentially enhancing the accumulation of annexins in the early stages of membrane repair.

Multisample lipidomic profiles of irritable bowel syndrome and irritable bowel syndrome-like symptoms in patients with inflammatory bowel disease: new insight into the recognition of the same symptoms in different diseases.

Overlapping clinical manifestations of irritable bowel syndrome (IBS) and IBS-like symptoms in patients with inflammatory bowel disease (IBD-IBS) present challenges in diagnosis and management. Both conditions are associated with alterations in metabolites, but few studies have described the lipid profiles. Our aim was to pinpoint specific lipids that contribute to the pathogenesis of IBS and IBD-IBS by analyzing multiple biologic samples. Diarrhea-predominant IBS (IBS-D) patients (n = 39), ulcerative colitis in remission with IBS-like symptoms patients (UCR-IBS) (n = 21), and healthy volunteers (n = 35) were recruited. IBS-D patients meet the Rome IV diagnostic criteria, and UCR-IBS patients matched mayo scores ≤ two points and Rome IV diagnostic criteria. Serum, feces, and mucosa were collected for further analysis. Lipid extraction was carried out by ultra-performance liquid chromatography-high resolution mass spectrometry (UPLC-HRMS). Lipidomics of mucosa and serum samples significantly differed among the three groups. Feces showed the most altered lipid species, and the enrichment analysis of 347 differentially abundant metabolites via KEGG pathway analysis revealed that alpha-linolenic acid metabolism was significantly altered in the two groups (P < 0.01). The ratio of omega-6/omega-3 fatty acid were imbalance in serum samples. This study revealed a comprehensive lipid composition pattern between IBS-D patients and UCR-IBS patients. We found several distinctive lipids involved in alpha-linolenic acid metabolism, reflecting an imbalance in the omega-6/omega-3 fatty acid ratio. Compared to mucosa and serum samples, fecal samples might have more advantages in lipidomics studies due to the convenience of sample collection and effectiveness in reflecting metabolic information.

Dynamic Brain Lipid Profiles Modulate Microglial Lipid Droplet Accumulation and Inflammation Under Ischemic Conditions in Mice.

Microglia are critically involved in post-stroke inflammation affecting neurological outcomes. Lipid droplet (LD) accumulation in microglia results in a dysfunctional and pro-inflammatory state in the aged brain and worsens the outcome of neuroinflammatory and neurodegenerative diseases. However, the role of LD-rich microglia (LDRM) under stroke conditions is unknown. Using in vitro and in vivo stroke models, herein accumulation patterns of microglial LD and their corresponding microglial inflammatory signaling cascades are studied. Interactions between temporal and spatial dynamics of lipid profiles and microglial phenotypes in different post-stroke brain regions are found. Hence, microglia display enhanced levels of LD accumulation and elevated perilipin 2 (PLIN2) expression patterns when exposed to hypoxia or stroke. Such LDRM exhibit high levels of TNF-α, IL-6, and IL-1β as well as a pro-inflammatory phenotype and differentially expressed lipid metabolism-related genes. These post-ischemic alterations result in distinct lipid profiles with spatial and temporal dynamics, especially with regard to cholesteryl ester and triacylglycerol levels, further exacerbating post-ischemic inflammation. The present study sheds new light on the dynamic changes of brain lipid profiles and aggregation patterns of LD in microglia exposed to ischemia, demonstrating a mutual mechanism between microglial phenotype and function, which contributes to progression of brain injury.

The Role of Food Matrices Supplemented with Milk Fat Globule Membrane in the Bioaccessibility of Lipid Components and Adaptation of Cellular Lipid Metabolism of Caco-2 Cells.

This study aimed to evaluate the digestive efficiency of food matrices supplemented with milk fat globule membrane isolated from buttermilk (BM-MFGM), using the INFOGEST in vitro digestion protocol hyphenated with the assessment of the digested material on the lipid profile of the Caco-2 cell culture model. First, we examined lipid profiles in food matrices supplemented with BM-MFGM and their subsequent digestion. The results showed distinct lipid profiles in different food matrices and micellar fractions. The presence of BM-MFGM lipids changed the cellular lipid profiles in Caco-2 cell cultures, with diverging contents in cholesteryl esters, triacylglycerides, and neutral lipids depending on the micellar food matrix factor. Hierarchical clustering analysis revealed patterns in cellular lipid responses to micellar stimuli, while volcano plots highlighted significant changes in cellular lipid profiles post-treatment. Thus, this study underscores the importance of in vitro digestion protocols in guiding food matrix selection for bioactive ingredient supplementation, elucidating intestinal epithelium responses to digested food stimuli.

Lipid metabolites are associated with the risk of osteoporotic fractures

We conducted this cross-sectional study to investigate the independent associations between lipid metabolites and osteoporotic fractures among participants aged 40–69 years from the UK Biobank. Serum lipid, lipoprotein levels and nuclear magnetic resonance (NMR) based metabolic biomarkers were measured at the baseline. We conducted multivariable logistic analyses to investigate potential independent associations between concentrations of lipid metabolites and osteoporotic fractures in both men and women. The odds ratios (ORs) for lipid metabolites were calculated based on their lowest tertile. Over a median follow-up period of 15 years, a total of 978 men and 4515 women were diagnosed with osteoporosis, whereas 138 men and 327 women encountered incident fractures. Statistically significant disparities were identified in NMR-based metabolic biomarkers among men and women with incident fractures compared to those without. Out of the 144 distinct lipid metabolites known, 35 exhibited significant associations with incident fractures in patients diagnosed with osteoporosis. Following the adjustment for confounding factors, degree of unsaturation (p = 0.0066) and docosahexaenoic acids (p = 0.0011) in male patients increased the risk of incident fractures. And high level of different metabolites of HDL (p = 0.0153), 3-Hydroxybutyrate (p = 0.0012) and Sphingomyelins (p = 0.0036) decreased the risk of incident fractures in female patients. This outcome indicates that these identified lipid metabolites may potentially have unique roles in independently contributing to the occurrence of osteoporotic fractures.

Cardiovascular risk in ANCA-associated vasculitis: Monocyte phenotyping reveals distinctive signatures between serological subsets

Background and aimsAnti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitides (AAV) is associated with an increased cardiovascular risk, particularly the myeloperoxidase AAV serotype (MPO-AAV). Distinct alterations in monocyte phenotypes may cause accelerated atherosclerotic disease in AAV. MethodsA cohort including 43 AAV patients and 19 healthy controls was included for downstream analyses. Extensive phenotyping of monocytes and monocyte-derived macrophages was performed using bulk RNA-sequencing and flow cytometry. An in vitro transendothelial migration assay reflecting intrinsic adhesive and migratory capacities of monocytes was employed. Subsequent sub-analyses were performed to investigate differences between serological subtypes. ResultsMonocyte subset analysis showed increased classical monocytes during active disease, whereas non-classical monocytes were decreased compared to healthy controls (HC). RNA-sequencing revealed upregulation of distinct inflammatory pathways and lipid metabolism-related markers in monocytes of active AAV patients. No differences were detected in the intrinsic monocyte adhesion and migration capacity. Compared to proteinase-3(PR3)-AAV, monocytes of MPO-AAV patients in remission expressed genes related to inflammation, coagulation, platelet-binding and interferon signalling, whereas the expression of chemokine receptors indicative of acute inflammation and monocyte extravasation (i.e., CCR2 and CCR5) was increased in monocytes of PR3-AAV patients. During active disease, PR3-AAV was linked with elevated serum CRP and increased platelet counts compared to MPO-AAV. ConclusionsThese findings highlight changes in monocyte subset composition and activation, but not in the intrinsic migration capacity of AAV monocytes. MPO-AAV monocytes are associated with sustained upregulation of inflammatory genes, whereas PR3-AAV monocytes exhibit chemokine receptor upregulation. These molecular changes may play a role in elevating cardiovascular risk as well as in the underlying pathophysiology of AAV.

Role of inflammatory biomarkers in mediating the effect of lipids on spontaneous intracerebral hemorrhage: a two-step, two-sample Mendelian randomization study.

Spontaneous intracerebral hemorrhage (sICH) is a form of stroke with high mortality rates and significant neurological implications for patients. Abnormalities in lipid metabolism have been implicated in various cardiovascular diseases, yet their relationship with sICH remains insufficiently explored, particularly concerning their association with inflammatory factors. Employing a two-sample, two-step Mendelian Randomization approach, combined with data from GWAS datasets, to investigate the causal relationship between plasma lipid levels and sICH. Additionally, the role of inflammatory factors in this relationship was examined, and sensitivity analyses were conducted to ensure the robustness of the results. The results indicate a significant causal relationship between 19 plasma lipid metabolites and sICH. Furthermore, mediation analysis revealed that three distinct lipids, namely Sterol ester (27:1/20:2), Phosphatidylcholine (16:0_20:4), and Sphingomyelin (d34:1), exert their influence on sICH through inflammatory factors. TRAIL (OR: 1.078, 95% CI: 1.016-1.144, p = 0.013) and HGF (OR: 1.131, 95% CI: 1.001-1.279, p = 0.049) were identified as significant mediators. This study provides new evidence linking abnormalities in lipid metabolism with sICH and elucidates the role of inflammatory factors as mediators. These findings contribute to a better understanding of the pathogenesis of sICH and offer novel insights and therapeutic strategies for its prevention and treatment.

Enhanced breast cancer therapy using multifunctional lipid-coated nanoparticles combining curcumin chemotherapy and nitric oxide gas delivery

The limitations associated with conventional cancer treatment modalities, particularly for breast cancer, underscore the imperative for developing safer and more productive drug delivery systems. A promising strategy that has emerged is the combination of chemotherapy with gas therapy. We synthesized curcumin-loaded amorphous calcium carbonate nanoparticles (Cur-CaCO3) via a gas diffusion reaction in the present study. Subsequently, a "one-step" ethanol injection method was employed to fabricate lipid-coated calcium carbonate nanoparticles (Cur-CaCO3@LA-Lip) loaded with L-arginine, aimed at harnessing the synergistic effects of chemotherapy and nitric oxide to enhance antitumor efficacy. Transmission electron microscopy analysis revealed that Cur-CaCO3@LA-Lip nanoparticles were subspherical with a distinct lipid layer encapsulating the periphery. Fourier transform infrared spectroscopy, X-ray powder diffraction, and differential scanning calorimetry results confirmed the successful synthesis of Cur-CaCO3@LA-Lip. The nanoparticles exhibited significant drug loading capacities of 8.89% for curcumin and 3.1% for L-arginine. In vitro and in vivo assessments demonstrated that Cur-CaCO3@LA-Lip nanoparticles facilitated sustained release of curcumin and exhibited high cellular uptake, substantial tumor accumulation, and excellent biocompatibility. Additionally, the nanoparticles showed robust cytotoxicity and potent antitumor efficacy, suggesting their potential as a formidable candidate for breast cancer therapy.