Free Lipid Research Articles

Comparative characterization of flavor precursors and volatiles in Chongming white goat of different ages by UPLC-MS/MS and GC–MS

Age has a significant impact on goat meat flavor. However, reporting the effects of age on free amino acid (FAAs), lipid profiles and aromas of goat meat is limited. Here, the FAAs, lipid profiles and aromas in the Chongming white goat with 12 months and 24 months were investigated in this study. A total 1164 lipids were identified using lipidomics, including 31 subclasses. Multivariate statistical analysis showed that 201 lipids had significant changes, FFA, TG and DG increased with goat age. Furthermore, the pathway analysis indicated that glycerophospholipid metabolism and glycerolipid metabolism were the key pathways that relate to lipid profile changes during goat growth. Thirty-five volatile compounds were identified, among them, 14 aromas with odor activity value greater than 1 were considered as potential characteristic aroma compounds of Chongming white goat meat. These findings reveal the FAAs, lipids, and aromas profiles in Chongming white goat meat are affected by age, which provides a basis for improving goat meat flavor.

Oral administration of butylated hydroxytoluene induces neuroprotection in a streptozotocin-induced rat Alzheimer’s disease model via inhibition of neuronal ferroptosis

BackgroundAlzheimer’s disease (AD) is the most common human neurodegenerative disorder worldwide. Owing to its chronic nature, our limited understanding of its pathophysiological mechanisms, and because of the lack of effective anti-AD drugs, AD represents a significant socio-economic challenge for all industrialized countries. Neuronal cell death is a key factor in AD pathogenesis and recent studies have suggested that neuronal ferroptosis may play a major patho-physiological role. Since ferroptosis involves free radical-mediated lipid peroxidation, we hypothesized that enteral administration of the radical scavenger butylated hydroxytoluene (BHT) might slow down or even prevent the development of AD-related symptoms in an in vivo animal AD model.Material and methodsTo test this hypothesis, we employed the rat model of streptozotocin-induced AD and administered butylated hydroxytoluene orally at a dose of 120 mg/kg body weight. Following BHT treatment, neuronal cell death was induced by bilateral stereotactic intraventricular injection of streptozotocin at a dose of 3.0 mg/kg body weight. Three weeks after surgery, we assessed the learning capabilities and the short-term memory of three experimental groups using the conventional y-maze test: (i) streptozotocin-treated rats (BHT pre-treatment), (ii) streptozotocin-treated rats (no BHT pre-treatment), (iii) sham-operated rats (BHT pre-treatment but no streptozotocin administration). After the y-maze test, the animals were sacrificed, hippocampal tissue was prepared and several biochemical (malonyl dialdehyde formation, glutathione homeostasis, gene expression patterns) and histochemical (Congo-red staining, Nissl staining, Perls staining) readout parameters were quantified.ResultsIntraventricular streptozotocin injection induced the development of AD-related symptoms, elevated the degree of lipid peroxidation and upregulated the expression of ferroptosis-related genes. Histochemical analysis indicated neuronal cell death and neuroinflammation, which were paralleled by aberrant intraneuronal iron deposition. The streptozotocin-induced alterations were significantly reduced and sometimes even abolished by oral BHT treatment.ConclusionOur data indicate that oral BHT treatment attenuated the development of AD-related symptoms in an in vivo rat model, most probably via inhibiting neuronal ferroptosis. These findings suggest that BHT might constitute a promising candidate as anti-AD drug. However, more work is needed to explore the potential applicability of BHT in other models of neurodegeneration and in additional ferroptosis-related disorders.

Toxicological analysis and anti-inflammatory and antioxidant evaluations of extract, fractions and secoxyloganin obtained from Guettarda viburnoides Cham. & Schltdl. in mice

Ethnopharmacological relevanceGuettarda viburnoides, "veludinho do campo," is traditionally used for the treatment of pain and inflammatory conditions in humans; however, only one scientific study has reported this effect in an ear inflammatory model. Therefore, it is necessary to explore other in vivo models and the chemical composition of this medicinal plant. Aim of the studyA chemical investigation of methanolic extract of G. viburnoides (MEGV) (leaves) led to the isolation of secoxyloganin (GV-1). In addition, the preclinical safety of MEGV (in acute and subacute toxicological models, gavage = p.o.), antioxidants of MEGV, ethyl acetate (EAFGV) and hydromethanolic (HMFGV) fractions were tested using free radical scavenging and lipid peroxidation methodologies, and the anti-inflammatory effects of MEGV, HMFGV and GV-1 (p.o.) were evaluated on carrageenan and complete Freund's adjuvant (CFA) models of inflammation in mice. Materials and MethodsMEGV was obtained from air-dried leaves by maceration with methanol at room temperature. MEGV was then purified by liquid-liquid partitioning, to obtain the EAFGV and HMFGV fractions. Purification of HMFGV afforded GV-1. The quantification of total phenols, flavonoids, flavonols, and condensed tannins was subsequently performed for MEGV. The antioxidant activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2, 2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid (ABTS) and oxidation of β-carotene were evaluated in MEGV and its fractions. The anti-inflammatory activity of MEGV (3, 30, and 100 mg/kg, p.o.) was assayed in carrageenan-induced models, followed by assessments of MEGV (100 mg/kg, p.o.), HMFGV (3 and 30 mg/kg, p.o.) and GV-1 (3 mg/kg, p.o.) in CFA- induced models in mice (including paw oedema, mechanical allodynia and cold sensitivity). Acute (14 days of MEGV, 2000 mg/kg, p.o.) and subacute (28 days, MEGV 30, 100, and 300 mg/kg, p.o.) toxicity was assessed in female Swiss mice. ResultsThe major compound was secoxyloganin (GV-1). The oral acute toxicity test of MEGV revealed no evidence of toxicity, indicating low toxicity according to the Organization for Economic Cooperation and Development (OECD) guidelines. In the subacute toxicity group, no clinical signs of toxicity or changes in body weight, water consumption, food consumption, or organ weight or morphology were observed after 28 days of gavage with MEGV (30, 100, and 300 mg/kg) compared with those in the control group. MEGV, EAFGV, and HMFGV showed significant free-radical scavenging and lipid peroxidation activities, with IC50 values ≤ 26.38 ± 4.56 μg/mL. In in vivo anti-inflammatory assays, MEGV (3, 30 and 100 mg/kg) reduced carrageenan-induced oedema (2 and 4 h) and hyperalgesia (3 and 4 h). In the CFA model, MEGV (100 mg/kg), HMFGV (30 mg/kg) and GV-1 (3 mg/kg) reduced inflammation (at 3, 4 and 24 h) in all parameters (oedema, mechanical allodynia and cold sensitivity). ConclusionThis study revealed that G. viburnoides has antioxidant and anti-inflammatory properties, and no toxicity was detected after acute or subacute gavage with MEGV, validating its traditional use in the treatment of inflammatory conditions.

Extracellular Hsp70 and Circulating Endometriotic Cells as Novel Biomarkers for Endometriosis.

Stress-inducible heat shock protein 70 (Hsp70), which functions as a molecular chaperone and is frequently overexpressed in different cancer cell types, is present on the cell surface of tumor cells and is actively released into the circulation in free and extracellular lipid vesicle-associated forms. Since the exact pathomechanism of endometriosis has not yet been elucidated (although it has been associated with the development of endometrial and ovarian cancer), we asked whether extracellular Hsp70 and circulating endometriotic cells (CECs) reflect the presence and development of endometriosis. Therefore, circulating levels of free and lipid microvesicle-associated Hsp70 were measured using the Hsp70-exo ELISA, and the presence of circulating CECs in the peripheral blood of patients with endometriosis was determined using membrane Hsp70 (mHsp70) and EpCAM monoclonal antibody (mAb)-based bead isolation approaches. Isolated CECs were further characterized by immunofluorescence using reagents directed against cytokeratin (epithelial marker), CD45 (leukocyte marker), CD105/CD44 (mesenchymal stemness markers) and by comparative RNA analysis. Similar to the situation in patients with cancer, the levels of circulating Hsp70 were elevated in the blood of patients with histologically proven endometriosis compared to a healthy control cohort, with significantly elevated Hsp70 levels in endometriosis patients with lesions outside the uterine cavity. Moreover, CECs could be isolated using the cmHsp70.1 mAb-based, and to a lesser extent EpCAM mAb-based, bead approach in all patients with endometriosis, with the highest counts obtained using the mHsp70-targeting procedure in patients with extra-uterine involvement. The longevity in cell culture and the expression of the cytokeratins CD105 and CD44, together with differentially expressed genes related to epithelial-to-mesenchymal transition (EMT), revealed similarities between mHsp70-expressing CECs and circulating tumor cells (CTCs) and suggest a mesenchymal stem cell origin. These findings support the involvement of mHsp70-positive stem cell-like cells in the development of endometriotic lesions. In summary, elevated levels of Hsp70 and CECs in the circulation could serve as liquid biopsy markers for endometriosis with extra-uterine involvement and help to elucidate the underlying pathomechanism of the disease.

MDH2 Promotes Hepatocellular Carcinoma Growth Through Ferroptosis Evasion via Stabilizing GPX4.

The crosstalk between tumor progression and ferroptosis is largely unknown. Here, we identify malate dehydrogenase 2 (MDH2) as a key regulator of ferroptosis. MDH2 deficiency inhibits the growth of hepatocellular carcinoma (HCC) cells and enhances their sensitivity to ferroptosis induced by RAS-selective lethal 3 (RSL3), a compound known to cause ferroptosis. MDH2 knock-down enhances RSL3-induced intracellular reactive oxygen species, free iron ions and lipid per-oxides levels, leading to HCC ferroptotic cell death which is rescued by ferrostatin-1 and iron chelator deferiprone. Importantly, the inhibition of HCC cell growth caused by MDH2 deficiency is partially rescued by ferroptosis blockade. Mechanistically, MDH2 resists RSL3-induced ferroptosis sensitivity dependent on glutathione peroxidase 4 (GPX4), an enzyme responsible for scavenging lipid peroxides, which is stabilized by MDH2 in HCC. The protein expressions of MDH2 and GPX4 are positively correlated with each other in HCC cell lines. Furthermore, through our UALCAN website analysis, we found that MDH2 and GPX4 are highly expressed in HCC samples. These findings reveal a critical mechanism by which HCC evades ferroptosis via MDH2-mediated stabilization of GPX4 to promote tumor progression and underscore the potential of MDH2 inhibition in combi-nation with ferroptosis inducers for the treatment of HCC.

IGF2/IGFBP4 reduces apoptosis and increases free cholesterol of chicken granulosa cells in vitro

Follicle selection, a crucial step in maintaining continuous egg production in chickens, is a process that relies on granulosa cells (GCs). In this study, we aimed to identify the key genes that are involved in follicle selection from our previous single-cell transcriptomic data. We used a combination of techniques and assays, including quantitative real-time PCR, immunofluorescence, Oil Red O staining, transmission electron microscopy (TEM), enzyme-linked immunosorbent assay (ELISA), monodansylcadaverine (MDC) assay, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay, cell counting Kit-8 (CCK-8) assay, and 5-ethynyl-2-deoxyuridine (EdU) assay. Multiple indices, such as cell proliferation, cell differentiation, progesterone synthesis, lipid droplet production, total and free cholesterol content, apoptosis, and autophagy, were measured to determine the states of GCs in vitro. The results demonstrated that overexpression of genes related to insulin-like growth factor 2 (IGF2) or IGF-binding protein 4 (IGFBP4) increases intracellular free cholesterol (progesterone precursors) and lipid droplet production, inhibits apoptosis through increased autophagy, and inhibits cell proliferation. This indicates that IGF2 or IGFBP4 can maintain the survival state and improve differentiation tendency of chicken granulosa cells in vitro. Therefore, this study provides new evidence on the functions of IGFs and IGFBPs in chickens, establishing a crucial experimental foundation for understanding the regulatory mechanisms of follicle selection. In addition, our study contributes to understanding follicular development and improves the egg-laying performance of chickens.

Chronic microcystin-leucine-arginine exposure induces osteoporosis by breaking the balance of osteoblasts and osteoclasts

Microcystin-leucine-arginine (MC-LR) produced by cyanobacterial harmful algal blooms are hazardous materials. However, the toxicity and mechanisms of continuous exposure to MC-LR on the occurrence of osteoporosis remains poorly documented. In this study, to mimic the chronic influences of MC-LR on the bone tissues in humans, an animal model was constructed in which mice were treated with MC-LR through drinking water at an environmentally relevant level (1–30 μg/L) for 6 months. MC-LR was enriched in the skeletal system, leading to the destruction of bone microstructure, the decrease of bone trabecular number, the reduction of osteoblasts, the enhanced content of lipid droplets, and the activation of osteoclasts, which is the characteristic of osteoporosis. Herein, we revealed ferroptosis is a vital mechanism of osteoblast death in mouse models of MC-LR. MC-LR exposure activates AMPK/ULK1 signaling, further promotes ferritin selective autophagy, causes free iron release and lipid peroxidation deposition, and eventually leads to ferroptosis of osteoblasts. Importantly, the use of AMPK or ferroptosis inhibitors in vivo markedly reduced MC-LR-induced osteoblast death and impaired osteogenic differentiation. Interestingly, MC-LR exposure promotes iron uptake in bone marrow macrophages through the TF-TFR1 pathway, leading to its transformation to TRAP-positive pre-osteoclast cells, thereby promoting bone resorption. Overall, our data innovatively revealed the core mechanism of MC-LR-induced osteoporosis, providing the bi-directional regulation of MC-LR on osteoblast-osteoclast from the perspective of iron homeostasis imbalance.

In vitro gastrointestinal digestibility and lipid oxidation of fish oil-in-water emulsions: Influence of different EPA/DHA ratios

The long-chain omega-3 polyunsaturated fatty acids (ω-3 PUFAs) eicosatetraenoic acid (EPA) and docosahexaenoic acid (DHA) are known to play roles in supporting human health, primarily by reducing inflammation and promoting its resolution. In this study, the impacts of EPA/DHA ratios (5.13/1, 2.45/1,1.34/1) on lipid oxidation and digestion behaviors were explored using an in vitro digestion model. Emulsions were characterzied by droplet size, zeta-potential as well as microstructure. Additionally, the release of free fatty acids (FFAs), lipid hydroperoxides (LPO) and thiobarbituric acid reactive substance (TBARS) were also investigaed throughout simulated digestion phases. Notably, for all EPA/DHA ratios, from saliva fluid to gastric fluid, droplet size was slightly changed, accompanied by a significant decrease in absolute zeta-potential, followed by an increase in both parameters after intestinal digestion. Emulsions with the lowest ratio of EPA/DHA (i.e., 1.34/1) exhibited lower FFA release compared to those with higher ratios (i.e., 5.13/1 and 2.45/1). Conversely, the lowest EPA/DHA ratio increased oxidation during the intestinal phase, as indicated by elevated LPO and TBARS levels. This study clearly suggests that EPA/DHA ratios influence the oxidative stability of fish oil emulisions during digestion and provides useful information to formulate fish oil supplementation that improves in vivo oxidative status.

Freezing storage combined with freeze-drying of black soldier fly (Hermetia illucens) larvae to produce oil rich in free lauric acid

Abstract The fat of Hermetia illucens larvae (black soldier fly, BSFL) is a rich source of lauric acid (LA), and its free fatty acid (FFA) form holds valuable potential for applications in food, feed, pharmaceuticals, or cosmetics. This study aimed to establish specific processing conditions of BSFL that naturally promote lipolysis, resulting in a high free LA (FLA) rich oil. Freezing was used for slaughtering, with different times of frozen storage (1, 7 and 14 d). Then, thermal (oven-drying) and non-thermal (freeze-drying) drying processes were compared. Additionally, the impact of 24 h restrictive vs non-restrictive feeding before slaughtering was tested. Free acidity, free fatty acid profile, lipid oxidation (peroxide value, PV; TBARs test) and antioxidant activity (DPPH test) were measured at days 0 and 30 of processing. Freeze-dried samples exhibited higher free acidity (42%) compared to oven-drying (4%), progressively increasing with frozen storage (24% at day 1 vs 51% at day 14). A restricted diet caused up to 60% free acidity. Nevertheless, the FFA profile was similar for both diet conditions, with LA as the major FFA (41% of total FFAs and 27% of total fat). After 30 days of storage, free acidity approached 70%. Oven-drying caused the highest PV (4.5 mEqO2/kg), especially after 14 d of frozen storage (>5.0 mEqO2/kg) and under restricted diet (6.1 mEqO2/kg). Conversely, freeze-drying maintained the lowest PV in all cases (0.6 mEqO2/kg). TBARs values mirrored the PV pattern. Antioxidant capacity was lower for freeze-drying compared to oven-drying (46% and 71%, respectively), regardless of frozen storage. Irrespective of the drying method, worse antioxidant activity was observed after restrictive diet. After 30 days of storage, the antioxidant activity decreased for all samples. The proposed strategy of freezing slaughtering, followed by frozen storage and freeze-drying offers a promising approach to naturally obtain a FLA-rich product from BSFL.

CHARMM36 All-Atom Gas Model for Lipid Nanobubble Simulation.

Lipid nanobubbles with different gas cores may integrate the biocompatibility of lipids, powerful physicochemical properties of nanobubbles, and therapeutic effects of gas molecules, which thus promote enormous biomedical applications such as ultrasound molecular imaging, gene/drug delivery, and gas therapy. In order for further more precise applications, the exact molecular mechanisms for the interactions between lipid nanobubbles and biological systems should be studied. Molecular dynamics (MD) simulation provides a powerful computational tool for this purpose. However, previous state-of-the-art MD simulations of free gas nanobubble/lipid nanobubble employed the vacuum as their gas cores, which is not suitable for studying the interactions between functional lipid nanobubbles and biological systems and revealing the biological roles of gas molecules. Hence, in this work, we developed and optimized the CHARMM36 all-atom gas parameters for six gases including N2, O2, H2, CO, CO2, and SO2, which accurately reproduced the gas density at different pressures as well as the spontaneous formation of gas nanobubbles. Subsequent applications of these gas parameters for lipid nanobubble simulations also reproduced the self-assembly process of the lipid nanobubble. We further developed a Python script to generate all-atom lipid nanobubble simulation systems, which was proven to be efficient for all-atom MD simulations of lipid nanobubbles and to be able to capture the exact dynamics of gas molecules at the gas-lipid and lipid-water interfaces of the lipid nanobubble. In summary, the all-atom gas models proposed in this work are suitable for simulating free gas nanobubbles and lipid nanobubbles, which are supposed to overcome the shortcomings of previous state-of-the-art MD simulations with the vacuum replacing the gas core and play key roles in revealing the molecular-level interactions between lipid nanobubbles and biological systems.

Ferritin Hinders Ferroptosis in Non-Tumorous Diseases: Regulatory Mechanisms and Potential Consequences.

Ferritin, as an iron storage protein, has the potential to inhibit ferroptosis by reducing excess intracellular free iron concentrations and lipid reactive oxygen species (ROS). An insufficient amount of ferritin is one of the conditions that can lead to ferroptosis through the Fenton reaction mediated by ferrous iron. Consequently, upregulation of ferritin at the transcriptional or posttranscriptional level may inhibit ferroptosis. In this review, we have discussed the essential role of ferritin in ferroptosis and the regulatory mechanism of ferroptosis in ferritin-deficient individuals. The description of the regulatory factors governing ferritin and its properties in regulating ferroptosis as underlying mechanisms for the pathologies of diseases will allow potential therapeutic approaches to be developed.

Enhanced ECCD36 signaling promotes skeletal muscle insulin resistance in female mice.

Consumption of a Western diet (WD) increases CD36 expression in vascular, hepatic, and skeletal muscle tissues promoting lipid metabolic disorders and insulin resistance. We further examined the role of endothelial cell-specific CD36 (ECCD36) signaling in contributing to skeletal muscle lipid metabolic disorders, insulin resistance, and their underlying molecular mechanisms. Female ECCD36 wild-type (ECCD36+/+) and knock-out (ECCD36-/-) mice, aged 6 wk, were provided with either a WD or a standard chow diet for a duration of 16 wk. ECCD36+/+ WD mice were characterized by elevated fasting plasma glucose and insulin levels, increased homeostatic model assessment for insulin resistance, and glucose intolerance that was blunted in ECCD36-/- mice. Improved insulin sensitivity in ECCD36-/- mice was characterized by increased phosphoinositide 3-kinases/protein kinase B signaling that further augmented glucose transporter type 4 expression and glucose uptake. Meanwhile, 16 wk of WD feeding also increased skeletal muscle free fatty acid (FFA) and lipid accumulation, without any observed changes in plasma FFA levels. These lipid metabolic disorders were blunted in ECCD36-/- mice. Moreover, ECCD36 also mediated in vitro palmitic acid-induced lipid accumulation in cultured ECs, subsequently leading to the release of FFAs into the culture media. Furthermore, consumption of a WD increased FFA oxidation, mitochondrial dysfunction, impaired mitochondrial respiratory, skeletal muscle fiber type transition, and fibrosis. These WD-induced abnormalities were blunted in ECCD36-/- mice. These findings demonstrate that endothelial-specific ECCD36 signaling participates in skeletal muscle FFA uptake, ectopic lipid accumulation, mitochondrial dysfunction, insulin resistance, and associated skeletal muscle dysfunction in diet-induced obesity.NEW & NOTEWORTHY ECCD36 exerts "extra endothelial cell" actions in skeletal muscle insulin resistance. ECCD36 is a major mediator of Western diet-induced lipid metabolic disorders and insulin resistance in skeletal muscle. Mitochondrial dysfunction is associated with diet-induced CD36 activation and related skeletal muscle insulin resistance.

Acidic Lysosome-Anchoring Croconium-Based Nanoplatform for Enhanced Triple-Mode Bioimaging and Fe3+-Triggered Tumor Synergistic Therapy.

Metal-modulated croconium dyes with multimodal-imaging and synergistic therapy in the tumor microenvironment have exhibited great potential in tumor theranostics. However, their unideal structure optimization always weakened the efficacy of near-infrared fluorescence-photoacoustic (NIRF/PA) imaging and photothermal therapy (PTT). Here, we screened croconium dye containing two indole groups with better NIRF/PA imaging and PTT in their family, linked to two morpholine rings, and obtained CR-736, as a lysosome-targeting and Fe3+-modulated agent. The established CR-736-Fe3+ nanoplatform was accurately delivered to the breast tumor site, released CR-736 and Fe3+ in the lower acidic lysosome microenvironment, and activated pH-responsive NIRF/PA/magnetic resonance imaging and PTT. Furthermore, ferroptosis generated hydroxyl free radicals and lipid peroxide by consuming GSH and H2O2 by dint of the accumulation of Fe3+ in tumor cells, which resulted in the inhibition of the expression of heat shock proteins and the concomitant recovery of PTT. The synergistic therapy of PTT, ferroptosis, and chemodynamics was further optimized to the maximal extent in tumor lysosome acidic microenvironment and proved both in vitro and a mouse tumor model. This study opens a new avenue in designing excellent and unique croconium-based nanoplatforms, synergizing multiple tumor theranostic methods, and further optimizing the theranostic effects in tumor microenvironment.

Co-exposure effect of different colour of LED lights and increasing temperature on zebrafish larvae (Danio rerio): Immunohistochemical, metabolomics, molecular and behaviour approaches

Although there are studies in the literature on the effects of different coloured light-emitting diodes (LEDs) on different organisms, there is limited information on how these effects change with temperature increase. In this study, the effects of blue, green, red and white LED lights on the early development process of zebrafish (Danio rerio (Hamilton, 1822)) were comprehensively investigated. In addition, to simulate global warming, it was examined how a one-degree temperature increase affects this process. For this purpose, zebrafish embryos, which were placed at 4 hpf (hours post fertilization) in an incubator whose interior was divided into four areas, were kept at three different temperatures (28, 29 and 30 °C) for 120 h. The group kept in a dark environment was chosen as the control. The temperature of the control group was also increased at the same rate as the other groups. The results showed that at the end of the exposure period, temperature and light colour caused an increase in body malformations. Histopathological damage and immunopositive signals of HSP 70 and 8-OHdG biomarkers in larval brains, increase in free oxygen radicals, apoptotic cells and lipid accumulation throughout the body, increase in locomotor activity, decrease in heart rate and blood flow, and significant changes in more than thirty metabolite levels were detected. In addition, it has been determined that many metabolic pathways are affected, especially glutathione, vitamin B6 and pyrimidine metabolism. Moreover, it has been observed that a one-degree temperature increase worsens this negative effect. It was concluded that blue light was the closest light to the control group and was less harmful than other light colours. The study revealed that blue light produced results that were most similar to those seen in the control group.

Applying chemical shift images (in-phase/opposed phased) for differentiating low-grade from high-grade glioma and comparison with magnetic resonance spectroscopy.

Grading gliomas is essential for treatment decisions and patient prognosis. In this study we evaluated the in-phase and out-of-phase sequences for distinguishing high-grade (HGG) from low-grade glioma (LGG) and the correlation with magnetic resonance spectroscopy (MRS) results. This observational study comprised patients with brain tumors referred to our center for brain MRS. The gold standard for diagnosis was based on the World Health Organization (WHO) glioma classification. Astandard tumor protocol was accomplished using a1.5‑T MRS scanner. Before contrast medium administration, extra in- and out-phase sequences were acquired. Three 20-30-mm2 oval regions of interest (ROIs) were placed in the solid component and the signal loss ratio (SLR) was calculated with the following formula: SLR tumor = (SI In phase - SI Opposed phase)/ SI In phase Correlations and comparisons between groups were made using the Pearson, chi-square and, independent samples t tests. Receiver operating characteristic (ROC) curve analysis was performed to assess the diagnostic performance. Statistical significance was set at p < 0.05. In total, 20 patients were included in the LGG and 13were included in the HGG group. The mean SLR in the HGG and LGG groups was 3.66 ± 2.12 and 1.63 ± 1.86, respectively (p = 0.01). There was astatistically significant correlation between lipid lactate (0.48, p = 0.004) and free lipid (0.44, p = 0.009) concentrations on MRS with SLR. The SLR is asimple, rapid, and noninvasive marker for differentiating between LGG and HGG. There is asignificant correlation with both the concentration and presence of free lipid and lipid-lactate peaks in MRS.

Effects of Intermittent Fasting and Sex on Blood Glucose, Free Fatty Acids, and Lipid Profile in Wistar Rats

Intermittent fasting (IF) has been reported to improve metabolic health through its effect on glucose and lipid profile. However, there is limited information on the effects of Intermittent Fasting on free fatty acids and sex related differences. This study was designed to investigate the effects of Intermittent Fasting (IF) on blood glucose, free fatty acids, lipid profile in both male and female Wistar rats and sex related differences. Twenty Wistar rats of both sexes weighing between 170-200g were used in the study. The animals were grouped into four (4) groups (n=5) per group. Groups 1 and 11 were male and female control groups respectively fed &amp;lt;i&amp;gt;ad libitum&amp;lt;/i&amp;gt; with feed and water while groups 111 and 1V were male and female intermittent fasting groups fasted for 16 hours and fed for 8 hours for 28 days respectively. They had free access to water for 24 hours. At the end of 28 days fasting, blood glucose, free fatty acids and lipid profile were determined. The results of the study showed that intermittent fasting was associated with a significant increase in free fatty acids in female rats (p&amp;lt; 0.05) but a non- significant increase in male rats. In both female and male rats, intermittent fasting was associated with a significant decrease (p&amp;lt; 0.05) ins blood glucose, total cholesterol, and low-density lipoprotein, but a non-significant decrease in triglyceride compared with control groups in both male and female rats. In conclusion, Intermittent fasting may help to improve blood glucose and maintain a balanced lipid profile in both males and females. However, Intermittent fasting may also raise the level of free fatty acids and the effect might be more pronounced in females.

Regulation of YAP translocation by myeloid Pten deficiency alleviates acute lung injury via inhibition of oxidative stress and inflammation

BackgroundPhosphatase and tensin homolog deleted on chromosome 10 (PTEN) is intricately involved in modulating the inflammatory response in acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). Nevertheless, the myeloid PTEN governing Hippo-YAP pathway mediated oxidative stress and inflammation in lipopolysaccharide (LPS)-induced ALI remains to be elucidate. MethodsThe floxed Pten (PtenFL/FL) and myeloid-specific Pten knockout (PtenM−KO) mice were intratracheal instill LPS (5 mg/kg) to establish ALI, then Yap siRNA mix with the mannose-conjugated polymers was used to knockdown endogenous macrophage YAP in some PtenM−KO mice before LPS challenged. The bone marrow-derived macrophages (BMMs) from PtenFL/FL and PtenM−KO mice were obtained, and BMMs were transfected with CRISPR/Cas9-mediated glycogen synthase kinase 3 Beta (GSK3β) knockout (KO) or Yes-associated protein (YAP) KO vector subjected to LPS (100 ng/ml) challenged or then cocultured with MLE12 cells. ResultsHere, our findings demonstrate that myeloid-specific PTEN deficiency exerts a protective against LPS-induced oxidative stress and inflammation dysregulated in ALI model. Moreover, ablation of the PTEN-YAP axis in macrophages results in reduced nuclear factor-E2-related factor-2 (NRF2) expression, a decrease in antioxidant gene expression, augmented levels of free radicals, lipid and protein peroxidation, heightened generation of pro-inflammatory cytokines, ultimately leading to increased apoptosis in MLE12 cells. Mechanistically, it is noteworthy that the deletion of myeloid PTEN promotes YAP translocation and regulates NRF2 expression, alleviating LPS-induced ALI via the inhibition of GSK3β and MST1 binding. ConclusionsOur study underscores the crucial role of the myeloid PTEN-YAP-NRF2 axis in governing oxidative stress and inflammation dysregulated in ALI, indicating its potential as a therapeutic target for ALI.

Simultaneous mitigation of heterocyclic aromatic amines and advanced glycation end products in roasted beef patties by plasma-activated water: Effects and mechanisms

Heterocyclic aromatic amines (HAAs) and advanced glycation end products (AGEs) are hazardous substances produced when food is heated. In this study, the ability of plasma-activated water (PAW) to simultaneously mitigate production of HAAs and AGEs in roasted beef patties was investigated. Assays of free radicals, lipid peroxidation, and active carbonyls were used to analyze the mechanisms. PAW treatment decreased the contents of free HAAs, free AGEs, bound HAAs, and bound AGEs to 12.65 ng/g, 0.10 μg/g, 297.74 ng/g, and 4.32 μg/g, with the inhibition rates of 23.88%, 23.08%, 11.02%, and 8.47%, respectively. PAW treatment decreased HAAs and AGEs and mitigated their increase during storage. The decrease of HAAs and AGEs in PAW-treated samples was correlated with the enhancement of antioxidant capacity. The increase of free radical scavenging ability by PAW treatment led to the decrease of lipid peroxidation and the decrease of active carbonyls, HAAs, and AGEs in meat products.

The antibacterial, antioxidant, and insecticidal activities of essential oils from Thymus vulgaris L., Salvia officinalis L., and Ocimum basilicum L.

AbstractThe essential oils from Thymus vulgaris, Salvia officinalis, and Ocimum basilicum were extracted by hydrodistillation, characterized by gas chromatography/mass spectrometry, and quantified by gas chromatography/flame ionization detector. The principal constituents were thymol, ρ‐cymene and carvacrol (T. vulgaris); camphor, β‐pinene, and 1,8‐cineole (S. officinalis); and (E)‐anethole, linalool, and 1,8‐cineole (O. basilicum). The essential oil from T. vulgaris was the most effective, forming inhibition halos of 46.16 ± 0.16 and 26.38 ± 0.33 mm, respectively, for Salmonella choleraesuis and Listeria monocytogenes. This essential oil was also more effective against S. choleraesuis, with a minimum inhibitory concentration of 8.85 mg mL−1, and a minimum inhibitory concentration of 17.71 mg mL−1 for L. monocytogenes. No bactericidal activity against S. choleraesuis and L. monocytogenes was observed for the essential oils from S. officinalis, and O. basilicum. Scanning electron micrographs showed that the addition of essential oils left the bacterial cells damaged and deformed. Significant 2,2‐diphenyl‐1‐picrylhydrazyl free radical scavenging capacity and lipid substrate protection were observed in the β‐carotene bleaching assay for the essential oil from T. vulgaris, with IC50 of 231.13 ± 0.53 and 15.25 ± 0.38 μg mL−1, respectively. A dose‐dependent relationship between antioxidant activity and concentrations was observed in the tests. Toxicities of LC50 = 1.24, 3.51 and 1.19 mg mL−1 against Drosophila suzukii flies, respectively, were observed for the essential oils from T. vulgaris, S. officinalis, and O. basilicum. Results suggest that essential oils can be promising antioxidant agents, insecticides, and inhibitors of pathogenic bacteria.

Streaming Potential and Associated Electrokinetic Effects through a Channel Filled with Electrolyte Solution Surrounded by a Layer of Immiscible and Dielectric Liquid.

The present article deals with the streaming potential-mediated pressure-driven flow across a channel in which the electrolyte solution is surrounded by a layer of cell membrane. Such a membrane of a biological cell may be modeled as an immiscible and dielectric liquid, which may bear free lipid molecules or charged surfactants. The presence of such additional charged molecules may lead to formation of liquid-liquid interfacial charge. In addition, the dielectric gradient-mediated ion partitioning effect further plays an important role in two-phase electrokinetic motion. We aim to study the generation of streaming potential and electrokinetic conversion efficiency as well as associated electroviscous effect for the undertaken problem. The mathematical model is based on the Poisson-Boltzmann equation for electrostatic potential and the Stokes equation for fluid flow, and the problem is studied considering suitable interfacial conditions for the flow variables along the liquid-liquid interface. The explicit analytical results for velocity and streaming field, electrokinetic energy conversion efficiency, and the parameter indicating the electroviscous effect are derived under the Donnan limit and within the Debye-Hückel electrostatic framework. We further numerically calculated the aforementioned intrinsic electrokinetic parameter associated with the problem undertaken for a wide range of pertinent parameters. The results are illustrated to indicate the impact of pertinent parameters on the generation of the streaming potential and associated electrokinetic effects.