Lower Lipid Levels Research Articles

Analysis of Metabolites and Metabolic Pathways of Three Chinese Jujube Cultivar.

Most studies on metabolites in jujube fruits focus on specific types of metabolites, but there are only a few comprehensive reports on the metabolites in jujube fruits. In order to understand the variance of metabolites in fruits of different jujube varieties. The objective of this study was to explore the metabolic components of jujube fruit by comparing three cultivars, namely Linyi LiZao (LZ), Jiaocheng SuantianZao (STZ), and Xianxian Muzao (MZ). The metabolites present in the fruits of these three cultivars were evaluated and compared. The results revealed the detection of 1059 metabolites across the three jujube varieties, with each cultivar exhibiting distinct metabolic characteristics. Notably, MZ exhibited a higher abundance of six metabolite classes, namely amino acids and derivatives, flavonoids, lipids, organic acids, phenolic acids, and terpenoids, compared to LZ. Conversely, LZ exhibited higher concentrations of alkaloids, lignans, coumarins, nucleotides, and their derivatives compared to the other two cultivars. In terms of STZ, its content of amino acids and derivatives, lignans and coumarins, organic acids, and phenolic acids was largely similar to that of LZ. However, the content of alkaloids, nucleotides, and their derivatives, and terpenoids was significantly higher in STZ compared to LZ. Additionally, STZ exhibited lower levels of flavonoids and lipids compared to LZ. Moreover, MZ was found to be less nutritionally rich than STZ, except for lignans and coumarins, as it displayed lower levels of all the metabolites. KEGG pathway enrichment analysis revealed six significantly different metabolic pathways (p < 0.05) between LZ and MZ, including arginine and proline metabolism, sphingolipid metabolism, flavonoid biosynthesis, glutathione metabolism, glycerophospholipid metabolism, and cysteine and methionine metabolism. The metabolites in STZ and MZ exhibited three significantly different pathways (p < 0.05), primarily associated with flavonoid biosynthesis, arginine and proline metabolism, and sphingolipid metabolism. The significantly differential metabolites between LZ and STZ were observed in the phenylpropionic acid biosynthesis pathway and the ubiquinone and other terpenoid-quinone biosynthesis pathways. LZ showed a closer relationship with STZ than with MZ. STZ and LZ exhibited higher medicinal values, while LZ had lower acidity and MZ displayed better antioxidant activity. This study presents the first thorough analysis of metabolites in LZ, STZ, and MZ cultivars, which can serve as a theoretical basis for quality analysis, functional research, and classification processing of jujube fruit.

Bifidobacterium longum CCFM1077 Attenuates Hyperlipidemia by Modulating the Gut Microbiota Composition and Fecal Metabolites: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

An increasing number of studies have indicated that gut microbiota and its metabolites are crucial in the development of hyperlipidemia. Bifidobacterium longum (B. longum) CCFM1077 has been shown to have lipid-lowering effects in animals. This study aimed to evaluate the potential of B. longum CCFM1077 in lowering the lipid levels in patients with hyperlipidemia and investigate the effect of this bacterium on serum lipid abnormalities, gut microbiota, and fecal metabolites in these patients. This study was a six-week, randomized, double-blind, and placebo-controlled pilot clinical trial. Subjects with hyperlipidemia (N = 62) were randomly assigned to receive placebo (N = 31) or B. longum CCFM1077 (1 × 1010 colony-forming units (CFUs) per day; N = 31). Serum lipid levels including total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), total triglyceride (TG), and high-density lipoprotein cholesterol (HDL-C) were examined at the baseline and interventional endpoints. Changes in the gut microbiota composition and diversity were measured based on 16S ribosomal RNA (rRNA) sequencing of the V3–V4 region at the end of the intervention period. Non-targeted metabolomics of the feces was performed using ultra-performance liquid chromatography (UPLC)-Q-Exactive Orbitrap/mass spectrometer. Oral administration of B. longum CCFM1077 for six weeks significantly decreased the serum levels of TC (p < 0.01) and LDL-C (p < 0.01) in patients with hyperlipidemia. B. longum CCFM1077 treatment markedly increased gut microbiota diversity and the relative abundance of anti-obesity-related genera, including Lactobacillus, Butyricicoccus, Bifidobacterium, and Blautia, whereas it decreased the relative abundance of obesity-related genera, including Alistipes, Megamonas, and Catenibacterium. Additionally, some key metabolites (bile acids (BAs), biotin, and caffeine) and their corresponding metabolic pathways (primary BA biosynthesis, and taurine and hypotaurine, biotin, purine, and caffeine metabolisms) were enriched by B. longum CCFM1077, and thus it may lower lipid levels. B. longum CCFM1077 is a probiotic strain with the potential to lower serum TC and LDL-C levels patients with hyperlipidemia. The underlying mechanism may be related to the increased abundance of anti-obesity-related genera and fecal metabolites. These findings provide a foundation for future clinical applications of lipid-lowering probiotics in managing individuals with hyperlipidemia.

A consortium of three-bacteria isolated from human feces inhibits formation of atherosclerotic deposits and lowers lipid levels in a mouse model

By a survey of metagenome-wide association studies (MWAS), we found a robust depletion of Bacteroides cellulosilyticus, Faecalibacterium prausnitzii, and Roseburia intestinalis in individuals with atherosclerotic cardiovascular disease (ACVD). From an established collection of bacteria isolated from healthy Chinese individuals, we selected B.cellulosilyticus, R.intestinalis, and Faecalibacterium longum, a bacterium related to F.prausnitzii, and tested the effects of these bacteria in an Apoe/- atherosclerosis mouse model. We show that administration of these three bacterial species to Apoe-/- mice robustly improves cardiac function, reduces plasma lipid levels, and attenuates the formation of atherosclerotic plaques. Comprehensive analysis of gut microbiota, plasma metabolome, and liver transcriptome revealed that the beneficial effects are associated with a modulation of the gut microbiota linked to a 7α-dehydroxylation-lithocholic acid (LCA)-farnesoid X receptor (FXR) pathway. Our study provides insights into transcriptional and metabolic impact whereby specific bacteria may hold promises for prevention/treatment of ACVD.

Assessment of Lipid Profile in Patients With Pulmonary Tuberculosis: An Observational Study.

Mycobacterium tuberculosis causes tuberculosis (TB), an infectious lung disease. There is mounting evidence linking low lipid levels to a variety of human diseases, including TB. Cholesterol, mainly due to its involvement in heart disease, gets more attention in recent years. The objectives of the study were to look into the link that connects hypolipidemia to the existence of pulmonary/extrapulmonary TB; we have tried to findthe link in relation to patients who have been recently diagnosed with TB as well as in those who are having TB in the long term. An observational study was performed on TB patients attending respiratory medicine at the Saveetha Medical College and Hospital,Chennai, Tamil Nadu, India, from February 2021 to January 2022, and their lipid levels were tested from patients with consent and correlated. Student's t-test was applied to the obtained data. To convey quantitative data, measurements such as mean along with standard deviation were applied, and a p-value of 0.05 was considered statistically significant. This research included 80 subjects, 40 of whom were diagnosed with TB, and the rest (40 controls) were deemed healthy. The age group with the highest low lipid levels in pulmonary TB was 40-50 years. A chi-square test of association was conducted; this test revealed that the fraction of TB patients having lower than normal levels of total cholesterol (p = 0.0001),triglyceridelevel(p = 0.006), high-density lipoprotein(p = 0.009), low-density lipoprotein(p = 0.006), and body mass index(p = 0.000) was statistically significantly higher in contrast to the control group. Thus, there was a significant correlation between a higher prevalence of hypolipidemia in patients with pulmonary tuberculosis (PTB) and normal healthy individuals. We observed a strong relationship between hypolipidemia and TB, indicating that patients with low lipid levels tend to have severe inflammation as compared to patients with normal lipid levels.

Abstract 677: Short Hydrocarbon-Stapled Apolipoprotein E Mimetic Peptides Enhance Lipoprotein Uptake

ApoE facilitates the clearance of apoB-containing lipoproteins by binding to heparan sulfate proteoglycans (HSPG), low density lipoprotein receptor (LDLR) and LDLR-related protein 1 (LRP1). ApoE has a receptor binding and a lipid binding domain, which are both needed for its biological function. Several apoE-based peptides have been developed that lower plasma lipid levels in animal models and in early-stage clinical trials. However, these peptides are long (28-61 residues), costly to synthesize and are potentially immunogenic as they often contain many amino acid substitutions that vary from the native apoE sequence. We developed novel short (10-12 residues) apoE mimetic peptides based on the apoE receptor binding region (residues 141-150) containing only 2 amino acid substitutions. We used hydrocarbon stapling to stabilize the native alpha helical structure of this region and to increase the lipid binding affinity of the peptides. In addition, octanoic or myristic acid was attached to the N-terminus of the peptides to further increase lipid binding affinity. Helical conformation and lipid binding of the peptides were confirmed by circular dichroism spectroscopy and phospholipid vesicle solubilization assay. Our peptides increased the uptake of fluorescent tagged VLDL and LDL in a concentration dependent manner (0.625-20 μM peptides) in both wild-type (WT) and LDLR knockout (KO) HepG2 cells as measured by flow cytometry. In addition, an all D-amino acid version of one of the peptides had a similar effect on LDL uptake as its all L-amino acid version. Altogether, this suggests that peptide-mediated uptake is LDLR independent. Treatment of WT HepG2 cells with heparinases diminished the low-dose effect (up to 2.5 μM) of the peptides on LDL uptake, indicating that HSPGs plays a role in peptide-mediated LDL uptake. Finally, the peptides (4.6 mg/kg, IV) lowered plasma total cholesterol (37% at 3h; 29% at 6h) and triglycerides (33% at 1h) in apoE-KO mice on a standard chow diet. In summary, the novel apoE peptides are shorter than previously reported peptides, are more similar to the native sequence of apoE, and are likely resistant to proteolysis, because of hydrocarbon stapling and, therefore, could potentially be developed into an oral therapy.

The positive association between antipsychotic-induced weight gain and therapeutic response: New biotypes of schizophrenia

Co-occurrence of antipsychotic-induced weight gain (AIWG) and therapeutic response (TR) did exist in clinic but was rarely studied. This study aims to identify potential TR/ AIWG biotypes and explore the clinical, genetic and neuroimaging features. This study enrolled 3030 patients to identify potential TR/AIWG biotypes and explore the clinical, genetic and neuroimaging features. We found three biotypes: TR+nonAIWG (46.91%), TR+AIWG (18.82%), and nonTR+nonAIWG (34.27%). TR+AIWG showed lower weight and lipid level at baseline, but higher changing rate, and higher genetic risk of obesity than TR+nonAIWG and nonTR+nonAIWG. GWAS identified ADIPOQ gene related to TR+AIWG biotypes and top-ranked loci enriched in one-carbon metabolic process, which related to both schizophrenia and metabolic dysfunction. Genetically predicted TR+AIWG was associated with higher odds of diabetes (OR=1.05). The left supplementary motor area was significantly negatively correlated with PRS of obesity. The distinguishing ability with multi-omics data to identify TR+AIWG reached 0.787. In a word, the “thin” patients with a higher risk of obesity are the target population of early intervention.

Raman spectroscopy-based biomarker screening by studying the fingerprint and lipid characteristics of Polycythem..a Vera cases blood serum

This study aimed to develop a novel approach for diagnosing Polycythemia Vera (PV), a stem cell-derived neoplasm of the myeloid lineage. The approach utilized Raman spectroscopy coupled with multivariate analysis to analyze blood serum samples collected from PV patients. The results showed that PV serum exhibited lower protein and lipid levels and structural changes in the functional groups that comprise proteins and lipids. The study also demonstrated differences in lipid biosynthesis and protein levels in PV serum. Using the Partial Least Square Discriminant Analysis (PLS-DA) model, Raman-based multivariate analysis achieved high accuracy rates of 96.49 and 93.04% in the training sets and 93.10% and 89.66% in the test sets for the 800–1800 cm-1 and 2700–3000 cm-1 ranges, respectively. The area under the curve (AUC) values of the test datasets were calculated as 0.92 and 0.89 in the 800–1800 cm-1 and 2700–3000 cm-1 spectral regions, respectively, demonstrating the effectiveness of the PLS-DA models for the diagnosis of PV. This study highlights the potential of Raman spectroscopy-based analysis in the early and accurate diagnosis of PV, enabling the application of effective treatment strategies.

HM-chromanone suppresses lipid accumulation by modulating AMPK/SREBP-1c pathway in ob/ob mice

This study investigated whether HM-chromanone, a bioactive compound isolated from Portulaca oleracea L., inhibits lipid accumulation in adipose tissue and liver of C57BL/6J ob/ob mice. C57BL/6J mice were used for the normal group and C57BL/6J ob/ob mice were randomly divided into three groups: ob/ob, metformin and HM-chromanone. In the HM-chromanone group, body and liver weight, fat mass and fat size were significantly lower than that in the ob/ob group. The HM-chromanone group also showed lower serum lipid levels and hepatic lipid accumulation compared with the ob/ob group. HM-chromanone administration significantly activated adenosine monophosphate-activated protein kinase (AMPK) and inhibited sterol regulatory element binding protein-1c (SREBP-1c), peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) in adipose tissue and liver. These results suggest that HM-chromanone potentially suppresses lipid accumulation by modulating AMPK/SREBP-1c pathway in adipose tissue and liver of ob/ob mice.

Efficacy of Mobile-Based Cognitive Behavioral Therapy on Lowering Low-density Lipoprotein Cholesterol Levels in Patients With Atherosclerotic Cardiovascular Disease: Multicenter, Prospective Randomized Controlled Trial.

Elevated low-density lipoprotein cholesterol (LDL-C) is an established risk factor for atherosclerotic cardiovascular disease (ASCVD). However, low adherence to medication and lifestyle management has limited the benefits of lowering lipid levels. Cognitive behavioral therapy (CBT) has been proposed as a promising solution. This trial aimed to evaluate the efficacy of mobile-based CBT interventions in lowering LDL-C levels in patients with ASCVD. This multicenter, prospective, randomized controlled trial enrolled 300 patients with ASCVD, who were randomly assigned to the mobile-based CBT intervention group and the control group in a ratio of 1:1. The intervention group received CBT for ASCVD lifestyle interventions delivered by WeChat MiniApp: "CBT ASCVD." The control group only received routine health education during each follow-up. The linear regression and logistic regression analyses were used to determine the effects of a mobile-based CBT intervention on LDL-C, triglyceride, C-reactive protein, the score of General Self-Efficacy Scale (GSE), quality of life index (QL-index), and LDL-C up-to-standard rate (<1.8 mmol/L) at the first, third, and sixth months. Finally, 296 participants completed the 6-month follow-up (CBT group: n=148; control group: n=148). At baseline, the mean LDL-C level was 2.48 (SD 0.90) mmol/L, and the LDL-C up-to-standard rate (<1.8 mmol/L) was 21.3%. Mobile-based CBT intervention significantly increased the reduction of LDL-C change (%) at the 6-month follow-up (β=-10.026, 95% CI -18.111 to -1.940). In addition, this benefit remained when baseline LDL-C <1.8 mmol/L (β=-24.103, 95% CI -43.110 to -5.095). Logistic regression analysis showed that mobile-based CBT intervention moderately increased the LDL-C up-to-standard rates (<1.8 mmol/L) in the sixth month (odds ratio 1.579, 95% CI 0.994-2.508). For GSE and QL-index, mobile-based CBT intervention significantly increased the change of scores (%) at the 1-, 3-, and 6-month follow-up (all P values <.05). In patients with ASCVD, mobile-based CBT is effective in reducing LDL-C levels (even for those who already had a standard LDL-C) and can improve self-efficacy and quality of life. Chinese Clinical Trial Registry ChiCTR2100046775; https://www.chictr.org.cn/showproj.aspx?proj=127140.

The pleiotropic effects of statins in rheumatoid arthritis.

Rheumatoid arthritis (RA) is an inflammatory and autoimmune disease. Studies over the past two decades suggest that statins have a beneficial impact on the complications associated with RA. These complications include RA disease activity and risk for cardiovascular diseases (CVD). This review aims to discuss the efficacy of statin therapy in RA. The current evidence suggests that statins' immunomodulatory and antioxidant properties significantly reduce disease activity and inflammatory response in patients with RA. In RA patients, the risk of CVD is reduced by statin treatment, and statin discontinuation is associated with an increased cardiovascular disease risk. The combined effect of statins on improving vascular function, lowering lipid levels, and reducing inflammation in RA patients is responsible for the decreased all-cause mortality in statin users. Further clinical studies are needed to ensure the therapeutic efficacy of statins in patients with RA.

The efficacy and potential mechanism of Danggui Buxue Decoction in treating diabetic nephropathy: A meta-analysis and network pharmacology

To evaluate the efficacy and potential pharmacological mechanisms of Danggui Buxue Decoction (DGBXD) in the treatment of diabetic nephropathy. Meta-analysis was used to conduct a comprehensive search of the literature for randomized controlled trials of DGBXD for diabetic nephropathy, followed by identification of quantitative literature based on inclusion and exclusion criteria, and statistical analysis of the included data using Review Manager. The network pharmacology technique was used to screen the chemical components of DGBXD and their targets, disease targets, shared targets, and other associated information, and then apply bioinformatics technologies to annotate the key pathways. Using AutoDock and PyMol software, the 6 core targets were docked with the 7 main active components of DGBXD. DGBXD complementary treatment significantly reduced 24 hours UTP, SCr and BUN levels and lowered blood glucose and lipid levels, improving clinical outcomes and modulating inflammatory factor levels. 22 active ingredients and 209 active targets were obtained for DGBXD, 245 core targets were obtained for diabetic nephropathy. The molecular docking results showed that all 7 components of DGBXD docked with 6 core targets had binding energies below -5. The findings suggest that DGBXD affects diabetic nephropathy through a multi-target, multi-component and multi-pathway mechanism.

Proof-of-concept study for liver-directed miQURE technology in a dyslipidemic mouse model

A gene-silencing platform (miQURE) has been developed and successfully used to deliver therapeutic microRNA (miRNA) to the brain, reducing levels of neurodegenerative disease-causing proteins/RNAs via RNA interference and improving the disease phenotype in animal models. This study evaluates the use of miQURE technology to deliver therapeutic miRNA for liver-specific indications. Angiopoietin-like 3 (ANGPTL3) was selected as the target mRNA because it is produced in the liver and because loss-of-function ANGPTL3 mutations and/or pharmacological inhibition of ANGPTL3 protein lowers lipid levels and reduces cardiovascular risk. Overall, 14 candidate miRNA constructs were tested invitro, the most potent of which (miAngE) was further evaluated in mice. rAAV5-miAngE led to dose-dependent (≤-77%) decreases in Angptl3 mRNA in WT mice with ≤-90% reductions in plasma ANGPTL3 protein. In dyslipidemic APOE∗3-Leiden.CETP mice, AAV5-miAngE significantly reduced cholesterol and triglyceride levelsvs. vehicle and scrambled (miSCR) controls when administrated alone, with greater reductions when co-administered with lipid-lowering therapy (atorvastatin). A significant decrease in total atherosclerotic lesion area (-58% vs. miSCR) was observed in AAV5-miAngE-treated dyslipidemic mice, which corresponded with the maintenance of a non-diseased plaque phenotype and reduced lesion severity. These results support the development of this technology for liver-directed indications.

Age and Genetic Risk Score and Rates of Blood Lipid Changes in China

Blood lipids are the primary cause of atherosclerosis. However, little is known about relationships between rates of blood lipid changes and age and genetic risk. To evaluate associations of blood lipid change rates with age and polygenic risk. This cohort is from the Prediction for Atherosclerotic Cardiovascular Disease Risk in China, which was established from 1998 to 2008. Participants were followed up until 2020 (mean [SD] follow-up, 13.8 [4.3] years) and received 4 repeated lipid measurements. Data analysis was performed from June to August 2022. A total of 47 691 participants with available genotype data were recruited, and 37 317 participants aged 18 years or older were included in the final analysis after excluding participants who were lost to follow-up or with major chronic diseases, and those without blood lipid measurements at baseline and any follow-up survey. Age and polygenic risk scores based on 126 lipid-related genetic variants. The estimated annual changes (EAC) of blood lipids in milligrams per deciliter. This study evaluated 37 317 participants (mean [SD] age of 51.37 [10.82] years; 15 664 [41.98%] were male). The associations of EACs of blood lipids with age differed substantially between male and female participants. Male participants experienced declining change as they got older for total cholesterol (EAC, 0.34 [95% CI, 0.14 to 0.54] mg/dL for age <40 years vs 0.01 [95% CI, -0.11 to 0.13] mg/dL for age ≥60 years), triglyceride (EAC, 3.28 [95% CI, 2.50 to 4.07] mg/dL for age <40 years vs -1.70 [95% CI, -2.02 to -1.38] mg/dL for age ≥60 years), and low-density lipoprotein cholesterol (LDL-C) (EAC, 0.15 [95% CI, -0.02 to 0.32] mg/dL for age <40 years vs 0.01 [95% CI, -0.10 to 0.11] mg/dL for age ≥60 years). Female participants had inverse V-shaped associations and the greatest rate of change appeared in the age group of 40 to 49 years (EAC for total cholesterol, 1.33 [95% CI, 1.22 to 1.44] mg/dL; EAC for triglyceride, 2.28 [95% CI, 1.94 to 2.62] mg/dL; and EAC for LDL-C, 0.94 [95% CI, 0.84 to 1.03] mg/dL). Change in levels of blood lipids were also associated with polygenic risk. Participants at low polygenic risk tended to shift toward lower blood lipid levels, with EACs of -0.16 (95% CI, -0.25 to -0.07) mg/dL; -1.58 (95% CI, -1.78 to -1.37) mg/dL; and -0.13 (95% CI, -0.21 to -0.06) mg/dL for total cholesterol, triglyceride, and LDL-C, respectively. Participants with high polygenic risk had the greatest rates of change for total cholesterol, triglyceride, and LDL-C (EAC, 1.12 [95% CI, 1.03 to 1.21] mg/dL; EAC, 3.57 [95% CI, 3.24 to 3.91] mg/dL; and EAC, 0.73 [95% CI, 0.65 to 0.81] mg/dL, respectively). Similar patterns were also observed across sex and age groups. In this cohort study, EACs of blood lipids were significantly associated with age and polygenic risk, suggesting that prevention strategies for lipids should focus on individuals with high genetic risk and in the critical age window.

Association between lipid levels and all-cause and cause-specific mortality in critically ill patients

Extremely low lipid levels are considered a sign of debilitation and illness. The association between lipid levels and the risk of mortality in critically ill patients has not been well investigated. This study was designed to evaluate the association between lipid levels and all-cause and cause-specific mortality in critically ill patients using a large collaborative research database known as the eICU database. In total, 27,316 individuals with low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC) and triglyceride (TG) measurements were analyzed. A J-shaped association was observed between LDL-C, HDL-C, and TC levels and all-cause and noncardiovascular mortality, with low concentrations associated with higher risk. LDL-C, HDL-C and TC levels in the first quintile were associated with higher all-cause and noncardiovascular mortality but not with cardiovascular mortality compared to the reference quintile. There was a marked synergistic effect between low LDL-C combined with low HDL-C on the risk of mortality. Individuals with LDL-C ≤ 96 mg/dL and HDL-C ≤ 27 mg/dL had an increased risk of all-cause mortality (OR 1.52, 95% CI: 1.26–1.82), cardiovascular mortality (OR 1.07, 95% CI: 1.37–1.76) and noncardiovascular mortality (OR 1.82, 95% CI: 1.37–2.43). The results of this observational cohort showed that low LDL-C, HDL-C and TC levels were independently associated with higher all-cause and noncardiovascular mortality in critically ill patients.

Combined Effects of Temperature and Dietary Lipid Level on Body Composition, Growth, and Freshness Profile in European Seabass, Dicentrarchus labrax.

A fish trial was carried out to evaluate the combined effects of temperature and dietary lipid level on the body composition, growth performance, and freshness profile of the European seabass (Dicentrarchus labrax). Fish were kept for 56 days at 20 °C and 24 °C and fed on two diets, with 16% and 20% lipid. At the end of the trial, fish were euthanized at two temperature conditions (0.6 °C or -0.6 °C) and kept on ice for 10 days at 4 °C to evaluate their freshness condition. Findings demonstrated that fish reared at 24 °C presented a lower lipid level and a higher daily growth index than those at 20 °C. Additionally, sensory analysis (Quality Index Method-QIM) and microbiological analysis revealed that fish reared at 24 °C showed better freshness conditions than those at 20 °C. However, the 16S rRNA metabarcoding analyses revealed a higher proliferation of genera associated with fish-spoiling bacteria in the skin microbiome of fish reared at 24 °C, i.e., Vibrio and Acinetobacter, which was not observed in the skin microbiome of fish reared at 20 °C. Nevertheless, the dietary lipid level did not have any influence on fish freshness. Therefore, our data suggest that the increase in temperature to 24 °C is beneficial for the growth and freshness profile (lower QIM and lower CFUs/cm2) of this particular species. Additionally, the lower euthanasia temperature (-0.6 °C) seems to lead to higher fish freshness than the normal temperature (0.6 °C).

Artificial Diets with Selective Restriction of Amino Acids and Very Low Levels of Lipids Induce Anticancer Activity in Mice with Metastatic Triple-Negative Breast Cancer.

Patients with metastatic triple negative breast cancer (TNBC) need new therapies to improve the low survival rates achieved with standard treatments. In this work, we show for the first time that the survival of mice with metastatic TNBC can be markedly increased by replacing their normal diet with artificial diets in which the levels of amino acids (AAs) and lipids are strongly manipulated. After observing selective anticancer activity in vitro, we prepared five artificial diets and evaluated their anticancer activity in a challenging model of metastatic TNBC. The model was established by injecting 4T1 murine TNBC cells into the tail vein of immunocompetent BALB/cAnNRj mice. First-line drugs doxorubicin and capecitabine were also tested in this model. AA manipulation led to modest improvements in mice survival when the levels of lipids were normal. Reducing lipid levels to 1% markedly improved the activity of several diets with different AA content. Some mice fed the artificial diets as monotherapy lived much longer than mice treated with doxorubicin and capecitabine. An artificial diet without 10 non-essential AAs, with reduced levels of essential AAs, and with 1% lipids improved the survival not only of mice with TNBC but also of mice with other types of metastatic cancers.

Substrates of Opposite Polarities and Downstream Processing for Efficient Production of the Biosurfactant Mannosylerythritol Lipids from Moesziomyces spp.

Biosurfactants can replace fossil-driven surfactants with positive environmental impacts, owing to their low eco-toxicity and high biodegradability. However, their large-scale production and application are restricted by high production costs. Such costs can be reduced using renewable raw materials and facilitated downstream processing. Here, a novel strategy for mannosylerythritol lipid (MEL) production explores the combination of hydrophilic and hydrophobic carbon sources sideways with a novel downstream processing strategy, based on nanofiltration technology. Co-substrate MEL production by Moesziomyces antarcticus was threefold higher than using D-glucose with low levels of residual lipids. The use of waste frying oil instead of soybean oil (SBO) in co-substrate strategy resulted in similar MEL production. Moesziomyces antarcticus cultivations, using 3.9 M of total carbon in substrates, yields 7.3, 18.1, and 20.1 g/L of MEL, and 2.1, 10.0, and 5.1 g/L of residual lipids, for D-glucose, SBO, and a combination of D-Glucose and SBO, respectively. Such approach makes it possible to reduce the amount of oil used, offset by the equivalent molar increase in D-glucose, improving sustainability and decreasing residual unconsumed oil substrates, facilitating downstream processing. Moesziomyces spp. also produces lipases that broken down the oil and, thus, residual unconsumed oils are in the form of free fatty-acids or monoacylglycerol, which are smaller molecules than MEL. Therefore, nanofiltration of ethyl acetate extracts from co-substrate-based culture broths allows to improve MEL purity (ratio of MEL per total MEL and residual lipids) from 66 to 93% using 3-diavolumes.

Deoxyguanosine kinase mutation F180S is associated with a lean phenotype in mice

BackgroundDeoxyguanosine kinase (DGUOK) deficiency is one of the genetic causes of mitochondrial DNA depletion syndrome (MDDS) in humans, leading to the hepatocerebral or the isolated hepatic form of MDDS. Mouse models are helpful tools for the improvement of understanding of the pathophysiology of diseases and offer the opportunity to examine new therapeutic options.MethodsHerein, we describe the generation and metabolic characterization of a mouse line carrying a homozygous DguokF180S/F180S mutation derived from an N-ethyl-N-nitrosourea-mutagenesis screen. Energy expenditure (EE), oxygen consumption (VO2) and carbon dioxide production (VCO2) were assessed in metabolic cages. LC-MS/MS was used to quantify plasma adrenal steroids. Plasma insulin and leptin levels were quantified with commercially available assay kits.ResultsMutant animals displayed significantly lower body weights and reduced inguinal fat pad mass, in comparison to unaffected littermates. Biochemically, they were characterized by significantly lower blood glucose levels, accompanied by significantly lower insulin, total cholesterol, high density lipoprotein and triglyceride levels. They also displayed an almost 2-fold increase in transaminases. Moreover, absolute EE was comparable in mutant and control mice, but EE in mutants was uncoupled from their body weights. Histological examination of inguinal white adipose tissue (WAT) revealed adipocytes with multilocular fat droplets reminiscent of WAT browning. In addition, mRNA and protein expression of Ucp1 was increased. Mutant mice also presented differing mitochondrial DNA content in various tissues and altered metabolic activity in mitochondria, but no further phenotypical or behavioral abnormalities. Preliminary data imply normal survival of DguokF180S/F180S mutant animals.ConclusionTaken together, DGUOK mutation F180S leads to a lean phenotype, with lower glucose, insulin, and lipid levels rendering this mouse model not only useful for the study of MDDS forms but also for deciphering mechanisms resulting in a lean phenotype.

Evaluation of Lipid Profile changes in children with urinary tract infections

Back ground: many researches about urinary tract infection has been conducted on adults but very little has been done on children. Therefore, this research is novel in Salahaddin city-Iraq.&#x0D; Urinary tract infection is a bacterial infection that affects part of the urinary tract. It affects the lower urinary tract as well as upper urinary tract. It is characterized by painful urination, urge to urinate or sometimes frequent urination. Other symptoms include fever in addition to flank pains.&#x0D; Bacteria infections cause a variety of changes in lipid profile concentrations by generating free radicals. Free radicals are reactive species generated by biochemical redox interactions that occur as a part of normal cell metabolism. These free radicals may cause lipid peroxidation and damage cellular structures of organism particularly erythrocytes and endothelium. Lipid peroxidation are free radicals mediated chain of reaction that, once initiated, results in oxidative deterioration of polyunsaturated lipids. The most common goal are components of biological membrane. When propagated in biological membranes, these reaction can be initiated or enhanced by a number of toxic products, including endoperoxides and aldehydes.&#x0D; Aim: The aims of this study were to evaluate the lipid profile of the children in acute phase of urinary tract infections.&#x0D; Methodology: Case-control study was designed to evaluate the lipid profile change in children with lower UTI. The study was performed on 130 children with ages between (4 – 12) years, 90 children with lower UTI (34.4% male) and (65.6% female,) and 40 control (45.0% male) and (55.0% female) in pediatric department of Salahaddin Teaching hospital from May 2017 till October 2017. The data were analyzed through the SPSS V.23 application, descriptive data analysis was done through frequency, percentage, mean, standard deviation in addition to T-test to compare results.&#x0D; Results: The results showed there was a significant decreased in the levels of Cholesterol, LDL, and HDL when compared to control group (144.02±17.69, 75.76±12.695, and 44.66±8.742 vs 167.65±13.13, 89.73±13.45, and 60.95±6.26 respectively), while there were a significant increase in triglycerides and VLDL in study group when compared to control group (118.03±18.66, and 23.56±3.76 vs 85.95±10.25, and 17.28±2.063 respectively).&#x0D; Conclusion: These observation shows that low levels of lipid, particularly total cholesterol, low density lipoprotein (LDL), high density lipoprotein (HDL) and increased triglycerides (TG) probably be

Statins in Children, an Update.

Since lipid abnormalities tend to progress from childhood to adulthood, it is necessary to early identify and treat children and adolescents with dyslipidemia. This is important in order to reduce the cardiovascular risk, delay the development of fatty streaks, slow the progression of atherosclerosis and reverse atherosclerotic plaques. Together with therapeutic lifestyle changes, statins are the most common lipid-lowering drugs. By inhibiting the endogenous cholesterol synthesis in the liver, statins increase the catabolism of LDL-C, reduce VLDL-C, IDL-C and TG and modestly increase HDL-C. Regardless of their lipid-lowering effect, statins have also pleiotropic effects. Statins have increasingly been prescribed in children and adolescents and mounting evidence suggests their beneficial role. As with adults, in children, several studies have demonstrated that statin therapy is efficient at lowering lipid levels and reducing CIMT progression and cumulative estimated atherosclerotic burden in children. Statins are generally very well-tolerated in both adults and children and adverse events are quite uncommon. When evaluating the need and the timing for statin treatment, the presence of several factors (secondary causes, familial history, additional risk factors) should also be considered. Before initiating statins, it is imperative for clinical practitioners to consult patients and families and, as with any new medication therapy, to monitor patients taking statins. Despite being safe and effective, many children with lipid disorders are not on statin therapy and are not receiving the full potential benefit of adequate lipid-lowering therapies. It is therefore important that clinicians become familiar with statins.