High Lipid Levels Research Articles

Effects of low temperature and highlight stress on lipid accumulation and cell structure of Tropidoneis maxima.

Tropidoneis maxima is a marine diatom with a rapid growth rate that produces high levels of lipids. To explore whether the lipid content could be further enhanced, cultures were first incubated under optimal conditions and then stressed under low temperature (10°C), a high light intensity level (80 μmol/m2 ·s), and the two factors together (interaction treatment). The results indicated that high light intensity and the temperature-light interaction exhibited greater impacts on lipid synthesis of T. maxima than low temperature. The two stress treatments increased lipid content by 17.16% and 16.6% compared to the control. In particular, higher biomass concentration was obtained with high light intensity (1.082 g L-1 ) and low temperature (1.026 g L-1 ). Moreover, high light intensity (9.06%) and interaction (10.3%) treatments yielded lower starch content compared to low temperature (14.27%) at the end of the stress culture. After 3 days of stress culture, the high light intensity treatment resulted in a 97.01% increase in cell wall thickness and an 18.46% decrease in cell diameter. The results suggest that high light intensity stress on T. maxima would open a new approach to cost-effective biolipid production.

Insights into the mechanism of growth and fat deposition by feeding different levels of lipid provided by transcriptome analysis of swamp eel (Monopterus albus, Zuiew 1793) liver.

Lipid is an important source of energy in fish feeds, and the appropriate fat content can improve the efficiency of protein utilization. However, excessive lipid content in the feed can lead to abnormal fat deposition in fish, which has a negative effect on the growth of fish. Therefore, the effects of feed lipid levels on swamp eel were studied. Essential functional genes were screened using transcriptomics. We divided 840 fish into seven groups (four replicates). A mixture of fish and soybean oils (1:4), 0%, 2%, 4%, 6%, 8%, 10%, and 12% was added to the basic feed were named groups one to seven (L1-L7), respectively. Isonitrogenous diets were fed swamp eel for 10 weeks. Growth performance, visceral index, nutritional components, and biochemical indexes were measured and analyzed. Livers of the 0%, 6%, and 12% groups were subjected to transcriptome sequencing analysis. The results of our study showed that: the suitable lipid level for the growth of swamp eel was 7.03%; the crude fat content of whole fish, liver, intestine, muscle, and skin increased with the increase of lipid level, with some significant difference, and excess fat was deposited in skin tissue; triglyceride, total cholesterol, and free fatty acid contents increased with the increase of feed lipid level. High-density lipoprotein levels in the L3 and L4 groups were higher than in the other groups. Blood glucose concentrations in the L5, L6, and L7 groups increased; the liver tissue structure was damaged when the lipid level was too high. two-hundred-and-twenty-eight differentially expressed genes were found. Several critical pathways regulating glucose metabolism and energy balance (e.g., glycerolipid metabolism, glycolysis synthesis, degradation of ketone bodies, and Janus Kinase/Signal Transducer and Activator of Transcription signaling pathway) were enriched in swamp eel compared with the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Suitable lipid levels (7.03%) can promote the growth of swamp eel, and excessive lipid levels can cause elevated blood lipids and lead to liver cell damage. Regulatory mechanisms may involve multiple metabolic pathways for glucose and lipid metabolism in eels. This study provides new insights to explain the mechanism of fat deposition due to high levels of lipid and provides a basis for the production of efficient and environmentally friendly feed for swamp eel.

Effect of hypercholestermic diet on the amyloid precursor protein (APP) deposition with some behavior alterations in male rats

Hypercholesterolemic diet (HCD) is unusually high lipid levels in blood and is strongly linked to brain damage and cerebrovascular illnesses. HCD is a chronic brain disorder characterized by cognitive impairment, inflammation, β-amyloid(Aβ) deposition. The goal of this study to investigate behavioral changes caused by the HCD in male rats. The experiment employed sixteen male rats, which was randomly split into two groups, the control group (8/ group) and the treated group (8/ group), which received a 1% cholesterol daily for 28 days. Results of behavioral test showed a significant increase (P≤0.0001) in Morris water maze test (MWM) and Elevated plus-maze test /open arm in treated group compared to control group , while a significant decrease (P≤0.0001) in Elevated plus-maze test / closed arm treated group as compared to control group. Fold change comparison between the groups expressed amyloid beta precursor protein (App) gene, this shows significant downregulation of the treatment group compared with control group. We concluded that a HCD has negative behavioral alteration that are linked to gene expression changes.

Association between serum lipid profile during the first and second trimester of pregnancy as well as their dynamic changes and gestational diabetes mellitus in twin pregnancies: a retrospective cohort study

BackgroundAbnormal lipid metabolism is associated with gestational diabetes mellitus (GDM) in singleton pregnancies. Data were lacking on twin pregnancies with GDM. We explored the association between serum lipid profiles in the first and second trimesters as well as their dynamic changes and GDM in twin pregnancies.MethodsThis was a retrospective cohort study of 2739 twin pregnancies that underwent a 75-g oral glucose tolerance test (OGTT) and were selected from the Beijing Birth Cohort Study from June 2013 to May 2021. Cholesterol (CHO), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels were measured at mean 9 and 25 weeks of gestation. We described maternal lipid levels in different tertiles that were associated with the risk of GDM stratified for age, pre-BMI, and fertilization type. GDM patients were divided into two groups according to OGTT: elevated fasting plasma glucose only (FPG group) and the rest of the GDM (non-FPG group). We estimated the relative risk of GDM with multivariable logistic regression models.ResultsIn this study, we found that 599 (21.9%, 599/2739) twin pregnancies developed GDM. They had increased CHO, TG, LDL, and LDL/HDL, decreased HDL levels in the first trimester, and increased TG as well as decreased HDL in the second trimester in univariate analyses, each P < 0.05. In multivariate analysis, when TG > 1.67 mmol/l (upper tertile) in elderly individuals, nonoverweight and ART groups increased the risk of GDM by 2.7-fold, 2.3-fold and 2.2-fold, respectively, compared with TG < 0.96 mmol/l (lower tertile). This effect remained in the abovementioned groups in the second trimester. Moreover, high TGs increased the risk of GDM in the FPG group (OR = 2.076, 95% CI 1.130–3.815) and non-FPG group (OR = 2.526, 95% CI 1.739–3.67) in the first trimester when TG > 1.67 mmol/l, and the rising risk in the non-FPG group as the TG tertile increased remained in the second trimester. HDL predominantly showed a negative association with elevated FPG in the second trimester (p < 0.05).ConclusionsTwin pregnancies with GDM have higher lipid levels. Increased TGs in the first and second trimesters are strongly associated with GDM, especially in elderly individuals, nonoverweight and ART groups. Lipid profiles varied among different GDM subtypes.

Lipid nanoparticle mRNA systems containing high levels of sphingomyelin engender higher protein expression in hepatic and extra-hepatic tissues

Lipid nanoparticles (LNPs) for delivery of mRNA usually contain ionizable lipid/helper lipid/cholesterol/PEG-lipid in molar ratios of 50:10:38.5:1.5, respectively. These LNPs are rapidly cleared from the circulation following intravenous (i.v.) administration, limiting uptake into other tissues. Here, we investigate the properties of LNP mRNA systems prepared with high levels of "helper" lipids such as 1,2-distearoyl-sn-glycero-3-phosphorylcholine (DSPC) or N-(hexadecanoyl)-sphing-4-enine-1-phosphocholine (egg sphingomyelin [ESM]). We show that LNP mRNAs containing 40 mol% DSPC or ESM have a unique morphology with a small interior "solid" core situated in an aqueous compartment that is bounded by a lipid bilayer. The encapsulated mRNA exhibits enhanced stability in the presence of serum. LNP mRNA systems containing 40 mol% DSPC or ESM exhibit significantly improved transfection properties invitro compared with systems containing 10 mol% DSPC or ESM. When injected i.v., LNP mRNAs containing 40 mol% ESM exhibit extended circulation lifetimes compared with LNP mRNA systems containing 10 mol% DSPC, resulting in improved accumulation in extrahepatic tissues. Systems containing 40 mol% ESM result in significantly improved gene expression in spleen and bone marrow as well as liver post i.v. injection compared with 10 mol% DSPC LNP mRNAs. We conclude that LNP mRNAs containing high levels of helper lipid provide a new approach for transfecting hepatic and extrahepatic tissues.

The relationship between inflammatory biomarkers and macular pigment optical density in hypertensive patients: a cross-sectional study.

Inflammation may be associated with macular pigment optical density (MPOD) degradation. The relationship between inflammation and MPOD is evaluated using inflammatory biomarkers, including high sensitivity C-reactive protein (hsCRP), lipid level and ratio, waist circumference (WC), and body mass index (BMI). In this cross-sectional design, 62 hypertensive patients were recruited between January 6 and January 8, 2022, at a primary care unit. The MPOD was measured using the Macular pigment screener II. Blood tests for hsCRP, lipid profile, WC measurement, BMI calculation, and completing a questionnaire were conducted, and statistical analysis was done by using Microsoft Excel 2019 and Stata version 16.1. Spearman's rank correlation test was used to evaluate correlations. Multivariate analysis for adjusting confounders was done by logistic regression. There was a significant negative correlation between hsCRP >3 and MPOD (r = -0.26, P = 0.04). Inflammation was linked to MPOD. Anti-inflammatory agents may be beneficial in preventing MPOD degradation.

Protective effect of ethanolic extract of Elettaria Cardamomum against gentamicin hepato-renal toxicity in male albino rats.

Cardamom is one of the spices containing a wide range of antioxidants and is used in medicinal preparations. Thus, in this study, we want to explore the protective effect of ethanolic cardamom extract on the liver-kidney toxicity caused by gentamicin in male albino rats. The experiment was applied to twenty-eight male albino rats divided randomly into four groups. The control group was given 1 ml/kg of saline orally. The gentamicin (GM) group was given a daily 80 mg/kg i.p of GM for seven days. Another group was given 100 or 200 mg/kg b.wt. p.o. ethanolic extract of Elettaria Cardamomum (EC) for seven days. Blood and liver-kidney samples were taken after the end of the study for analyses to test for liver-kidney function and lipid profile (LP). Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and bilirubin activities were higher in the GM group than in the control group. However, the groups' differences in globulin levels and total protein (TP) were not statistically significant. Compared to the control group, the albumin level in the gentamicin group was considerably lower. On the other hand, creatinine and urea levels, lipid, serum total cholesterol levels, and high-density lipoprotein (HDL) significantly increased in the gentamicin group but decreased in the control group and co-treated groups with gentamicin and ethanolic extract EC. Low-density lipoprotein (LDL) significantly dropped, while the control group showed high levels of lipid and serum total cholesterol. EC ethanolic extract shields the liver-kidney against GM harmful effects in male rats. Recent research demonstrated that the effects of the plant cardamom were the same at both low-high doses. The phenolic elements in EC may be responsible for this protective effect.

Oxidative stability of white striping chicken breasts: effect of cold storage and heat treatments

This study aimed to investigate the level of lipid and protein oxidation in poultry breasts with severe white striping (WS; striation thickness > 1 mm) and nonaffected meats (N; normal breast) during storage under refrigeration (1°C for 14 d) and freezing (-18°C for 90 d). WS presented higher lipid content, although no difference in protein content was detected, compared to normal broiler breast (N). Regarding oxidative damages, a reduction in malondialdehyde and carbonyl protein, hexanal, octanal and nonanal levels, alongside the interaction of these compounds with other compounds in raw, roasted, and reheated breasts was observed under refrigerated storage (14 d). Freezing storage promotes an increase in carbonyls proteins, hexanal, octanal and nonanal levels at 45 d of storage in poultry meats and subsequent decrease, indicating the evolution of oxidative reactions. Regardless of the type of storage, in general, breasts with WS myopathy have higher levels of lipid and protein oxidation.

Optimization of photosynthetically active radiation, temperature, and urea deprivation for increasing neutral lipids and fatty acids in Scenedesmus obliquus and Chlorella vulgaris as biodiesels

The present study investigated the impact of photosynthetically active radiation (PAR), culture temperature, and urea addition on the biomass, total lipid, lipidomic profile, and fatty acid productivity in Scenedesmus obliquus (S. obliquus) and Chlorella vulgaris (C. vulgaris) for sustainable biodiesels. In this study, S. obliquus and C. vulgaris, respectively, showed generally high cell densities with 1.23 g/L and 1.22 g/L of dried cell weights and 18.2% and 17.65% of lipids. Of the various PARs tested (10, 20, 40, and 60 μmol/m2/sec), 60 μmol/m2/sec showed maximal biomass yields for both species (1.78 g/L of dried cell weight and 25.7% of lipids for S. obliquus; and 1.74 g/L of dried cell weight and 24.6% of lipids for C. vulgaris). Of the various temperatures (27 °C, 37 °C, and 47 °C), 27 °C showed maximal dried cell weights (1.22 g/L for S. obliquus and 1.23 g/L for C. vulgaris), whereas 47 °C accumulated high levels of lipids (23.5% for S. obliquus and 21.6% for C. vulgaris). On the other hands, urea deprivation in the medium increased lipid levels in both species compared to no deprivation (10% increase for S. obliquus and 8% increase for C. vulgaris). The fatty acid profile showed that palmitic acid with 16 carbons and double bonds was dominant among major fatty acids, accounting for 30.55% for S. obliquus and 26.6% for C. vulgaris. Furthermore, urea deprivation and 60 μmol/m2/sec of PAR showed the highest proportions of unsaturated fatty acids in both species (27.55% for urea deprivation and 30.55% for PAR in S. obliquus; and 28.33% for urea deprivation and 26.6% for PAR in C. vulgaris).

Colloidal Drug Delivery of Simvastatin for Prolonged Drug Release and Increased Bioavailability

Hyperlipidemia is the major cause of atherosclerosis in which the lipid level in the blood plasma increases which leads to the formation of atherosclerotic plaque in the blood stream. Antihyperlipidemic drugs are used to reduce the high level of lipids and lipoproteins in the blood. HMG CoA reductase (Statin drugs) are the most potent group of antihyperlipidemic drugs and it works by inhibiting the Hydroxymethylglutaryl-coenzyme A (HMG CoA) reductase enzyme in the cholesterol synthesis. The most commonly used drug for decreasing low density lipoprotein (LDL) cholesterol is simvastatin. I is more efficacious as compared to Atorvastatin in increasing high density lipoprotein (HDL) cholesterol level. Simvastatin (SIM) is lipophilic in nature and is a perfect candidate for a novel colloidal drug delivery system (CDDS). CDDS delivers the drug to its target site to enhance the control release and to achieve the maximum therapeutic effect. This concept of targeting includes the nanoparticulate system such as Liposomes, Solid lipid nanoparticles (SLNs), Polymeric nanoparticles, Niosomes, Nanoemulsion and Metallic nanoparticles.

Growth of Dunaliella viridis in multiple cycles of reclaimed media after repeated high pH-induced flocculation and harvesting

Minimizing the use of water for growing microalgae is crucial for lowering the energy and costs of animal feed, food, and biofuel production from microalgae. Dunaliella spp., a haloterant species that can accumulate high intracellular levels of lipids, carotenoids, or glycerol can be harvested effectively using low-cost and scalable high pH-induced flocculation. However, the growth of Dunaliella spp. in reclaimed media after flocculation and the impact of recycling on the flocculation efficiency have not been explored. In this study, repeated cycles of growth of Dunaliella viridis in repeatedly reclaimed media from high pH-induced flocculation were studied by evaluating cell concentrations, cellular components, dissolved organic matter (DOM), and bacterial community shifts in the reclaimed media. In reclaimed media, D. viridis grew to the same concentrations of cells and intracellular components as fresh media—107 cells/mL with cellular composition of 3 % lipids, 40 % proteins, and 15 % carbohydrates—even though DOM accumulated and the dominant bacterial populations changed. There was a decrease in the maximum specific growth rate and flocculation efficiency from 0.72 d−1 to 0.45 d−1 and from 60 % to 48 %, respectively. This study shows the potential of repeated (at least five times) flocculation and reuse of media as a possible way of reducing the costs of water and nutrients with some tradeoffs in growth rate and flocculation efficiency.

Effect of Ajwa Date and Germinated Barley on Lipid Profile in Rats Fed High-Fat Diet

High levels of lipids and cholesterol, particularly LDL, in blood are considered the most common risk factors for cardiovascular diseases that threaten human life. Recently, interest has increased in the use of medicinal plants to treat various diseases due to their lack of side effects. The current study aims to investigate the effect of Ajwa date (AD) and germinated barley (GB) on the lipid profile in rats fed a high-fat diet (HFD). Thirty rats were distributed into five groups (six per group) as follows: the negative control group, the positive control group fed a HFD, and the other three groups that were fed a HFD supplemented with a mixture of AD and GB in equal ratios with different proportions of 20, 30, and 40% in the diet. There was an increase in moisture, protein, phenols, and vitamin C content and a decrease in the content of ash, carbohydrates, fats, and beta-glucans in GB. Blood total cholesterol levels decreased significantly (83.53, 70.12, and 73.55 mg/dL) in the groups fed the AD and GB mixtures in different percentages (20, 30, and 40%). Likewise, the AD and GB mixtures recorded a significant decrease in the level of triglycerides in the treated groups, with no significant effect on the high-density lipoprotein and low-density lipoprotein. There was a significant improvement in the level of alanine aminotransferase, while the level of aspartate aminotransferase was not affected by the treatment. In summary, AD and GB mixtures can modulate the lipid profile alterations caused by HFD through their phytochemical constituents, particularly beta-glucans.

Maternal high-fat diet increases the susceptibility of offspring to colorectal cancer via the activation of intestinal inflammation.

A high-fat diet plays a key role in the pathogenesis of colorectal cancer, and this effect on the gut can also occur in the offspring of mothers with a high-fat diet. In this review, we discuss the role of a high-fat diet in the pathogenesis of colorectal cancer and summarize the effects of a maternal high-fat diet on the activation of inflammation and development of colorectal cancer in offspring. Studies have found that a maternal high-fat diet primarily induces an inflammatory response in the colorectal tissue of both the mother herself and the offspring during pregnancy. This leads to the accumulation of inflammatory cells in the colorectal tissue and the release of inflammatory cytokines, which further activate the NF-κb and related inflammatory signaling pathways. Research suggests that high levels of lipids and inflammatory factors from mothers with a high-fat diet are passed to the offspring through the transplacental route, which induces colorectal inflammation, impairs the intestinal microecological structure and the intestinal barrier, and interferes with intestinal development in the offspring. This in turn activates the NF-κb and related signaling pathways, which further aggravates intestinal inflammation. This process of continuous inflammatory stimulation and repair may promote the uncontrolled proliferation of colorectal mucosal cells in the offspring, thus increasing their susceptibility to colorectal cancer.

Deciphering the underlying mechanisms of the oxidative perturbations and impaired meat quality in Wooden breast myopathy by label-free quantitative MS-based proteomics

The study aimed to investigate biochemical mechanisms occurred in Wooden breast (WB) chicken meat, with attention to the impact on meat quality. Commercial chicken breasts were classified as Normal (N, n = 12), WB-M (moderate degree; focal hardness on cranial region, n = 12) and WB-S (severe degree; extreme and diffused hardness over the entire surface, n = 12). Samples were analyzed for physico-chemical properties, oxidative damage to lipids and proteins, and discriminating sarcoplasmic proteins by using a Q-Exactive mass spectrometer. WB meat presented impaired composition and functionality and higher levels of lipid and protein oxidation markers than N meat. The proteomic profile of WB-S presents a dynamic regulation of the relevant proteins involved in redox homeostasis, carbohydrate, protein and lipid metabolisms. Proteomics results demonstrate that the physiological and metabolic processes of muscles affected by WB myopathy are involved in combating the inflammatory process and in repairing the damaged tissue by oxidative stress.

Bariatric surgery shown to reverse diabetes related neuropathic complications among people with obesity

Bariatric surgery is increasingly been utilized to induce and maintain significant weight loss among patients with obesity. For patients with diabetes, bariatric surgery is associated with increased likelihood of reversal of type 2 diabetes; however, its impact on long-term diabetes related neuropathic complications remain unclear. This is particularly relevant given the potential increased risk of “treatment-induced neuropathy” associated with rapid improvements of glucose control. A study undertaken by research team from the University of Michigan have now reported that bariatric surgery may improve neuropathy by regenerating damaged nerves. In the study published in the journal Diabetologia, 120 patients who underwent bariatric surgery for obesity were followed up for over 2 years after the procedure. Metabolic risk factors such as high glucose, high blood pressure and lipid levels were significantly improved. The researchers also assessed two primary measures for peripheral neuropathy in patients with obesity by undertaking skin biopsies to assess nerve fibre density in the thigh and the leg. They observed that 2 years after bariatric surgery, nerve fibre density improved in the thigh and remained stable in the leg. This is particularly relevant given that the natural history of peripheral neuropathy among patients with obesity is often associated with a decline in nerve function, thus, stability in nerve fibre density is considered to be a good outcome. Furthermore, the observed improvement in nerve fibre density at the thigh indicate that bariatric surgery may be a successful therapy to improve or reverse peripheral neuropathy for patients with long-term metabolic impairment. This finding advances current therapeutic options for peripheral neuropathy, especially in patients with obesity which currently focuses on analgesia and neuropathic oral treatment such as gabapentin, amitriptyline, duloxetive, topical analgesics and non-medical treatments, like acupuncture and cognitive behavioural therapy.

Current status and time trends of lipid and use of statins among older adults in China-real world data from primary community health institutions.

Elevated serum total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels are established risk factors for cardiovascular diseases, a leading cause of death in China, especially in aged population. We sought to assess the latest levels of serum lipids, prevalence of dyslipidemia and achievement of LDL-C lowering targets among Chinese aged population. The data was obtained from the annual health check and medical records in primary community health institutions of Yuexiu District, Guangzhou, Southern China. A sample of approximately 135,000 participants provides comprehensive estimates of the status of cholesterol level and statins use in older adults in China. Clinical characteristics were compared by different age grades, genders and years. Independent risk factors associated with statin use were determined by stepwise logistic regression analysis. The mean levels of TC, HDL-C, LDL-C, TG were 5.39, 1.45, 3.10, and 1.60 mmol/L, respectively, while the prevalence of high TC, high TG, high LDL-C, and low HDL-C were 21.99, 15.52, 13.26, and 11.92%, respectively. Although statin use showed an increasing trend in both participants > 75 years and ≤75 years of age, the achievement of treatment goals fluctuated between 40.94 and 48.47%, and even seemed to have a downward trend. Stepwise multiple logistic regression analysis further indicated that age, medical insurance, ability of self-care, hypertension, stroke, CAD, and high LDL-C were shown to be associated with statins use (P < 0.05). Those aged ≤75 years old seemed to be less likely to use statin, and those without medical insurance or ability of self-care seemed to be less likely to use statin, too. Patients with hypertension, stroke, CAD and high LDL-C were more inclined to use statins. Chinese aged population currently experienced high serum lipid levels and prevalence of dyslipidemia. Although an increasing trend was shown in the proportion of high CVD risk and statin use, the achievement of treatment goals seemed to have a downward trend. Improvement of lipid management is necessary in order to reduce the burden of ASCVD in China.

Untargeted Lipidomics Method for the Discrimination of Five Crab Species by Ultra-High-Performance Liquid Chromatography High-Resolution Mass Spectrometry Combined with Chemometrics.

In this study, ultra-high-performance liquid chromatography high-resolution accurate mass-mass spectrometry (UHPLC-HRAM/MS) was applied to characterize the lipid profiles of five crab species. A total of 203 lipid molecular species in muscle tissue and 176 in edible viscera were quantified. The results indicate that Cancer pagurus contained high levels of lipids with a docosahexaenoic acid (DHA) and eicosapntemacnioc acid (EPA) structure in the muscle tissue and edible viscera. A partial least squares discriminant analysis (PLS-DA) showed that PE 16:0/22:6, PE P-18:0/20:5, PA 16:0/22:6 and PC 16:0/16:1 could be used as potential biomarkers to discriminate the five kinds of crabs. In addition, some lipids, such as PE 18:0/20:5, PC 16:0/16:1, PE P-18:0/22:6 and SM 12:1;2O/20:0, could be used as characteristic molecules to distinguish between Cancer magister and Cancer pagurus, which are similar in appearance. This study provides a new perspective on discriminating crab species from MS-based lipidomics.

Dyslipidemia in the First 100 days and the Association with Acute Graft-versus-host Disease after Allogeneic Stem Cell Transplantation: A Single-center Retrospective Study in China

Dyslipidemia is a common complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The interaction between post-transplant hyperlipidemia and acute graft-versus-host disease (aGVHD) is uncertain. In this study, we performed a retrospective study to explore the relationship between dyslipidemia and aGVHD and the potential mechanism of aGVHD on dyslipidemia in 147 recipients who underwent allo-HSCT. The lipid profiles, transplantation details, and other laboratory data of the subjects were collected in the first 100 days post-transplantation. Our results indicated 63 patients with new-onset hypertriglyceridemia and 39 patients with new-onset hypercholesterolemia. A total of 57 (38.8%) patients developed aGVHD after transplantation. In a multifactorial analysis, aGVHD was an independent factor in the development of dyslipidemia in recipients (P < 0.05). After transplantation, the median LDL-C level of patients with aGVHD was 3.04 mmol/L (standard deviation value (SD): 1.36 mmol/L, 95% confidence interval (CI): 2.62, 3.45 mmol/L), and the LDL-C level in patients without aGVHD was 2.51 mmol/L (SD: 1.38 mmol/L, CI: 2.67, 3.40 mmol/L) (P < 0.05). Female recipients had higher lipid levels than males (P < 0.05). LDL levels (≥ 3.4 mmol/L) post-transplant were an independent risk factor for the development of aGVHD (OR = 0.311, P < 0.05). In conclusion, larger sample studies are anticipated to confirm our preliminary result, and an accurate mechanism between lipid metabolism and aGVHD needs to be determined in the future.

Virtual Screening of Novel 24-Dehydroxysterol Reductase (DHCR24) Inhibitors and the Biological Evaluation of Irbesartan in Cholesterol-Lowering Effect

Hyperlipidemia is a risk factor for the development of fatty liver and cardiovascular diseases such as atherosclerosis and coronary heart disease, and hence, cholesterol-lowering drugs are considered important and effective in preventing cardiovascular diseases. Thus, researchers in the field of new drug development are endeavoring to identify new types of cholesterol-lowering drugs. 3β-hydroxysterol-Δ(24)-reductase (DHCR24) catalyzes the conversion of desmosterol to cholesterol, which is the last step in the cholesterol biosynthesis pathway. We speculated that blocking the catalytic activity of DHCR24 could be a novel therapeutic strategy for treating hyperlipidemia. In the present study, by virtually screening the DrugBank database and performing molecular dynamics simulation analysis, we selected four potential DHCR24 inhibitor candidates: irbesartan, risperidone, tolvaptan, and conivaptan. All four candidates showed significant cholesterol-lowering activity in HepG2 cells. The experimental mouse model of hyperlipidemia demonstrated that all four candidates improved high blood lipid levels and fat vacuolation in the livers of mice fed with a high-fat diet. In addition, Western blot analysis results suggested that irbesartan reduced cholesterol levels by downregulating the expression of the low-density lipoprotein receptor. Finally, the immune complex activity assay confirmed the inhibitory effect of irbesartan on the enzymatic activity of DHCR24 with its half-maximal inhibitory concentration (IC50) value of 602 nM. Thus, to the best of our knowledge, this is the first study to report that blocking the enzymatic activity of DHCR24 via competitive inhibition is a potential strategy for developing new cholesterol-lowering drugs against hyperlipidemia or multiple cancers. Furthermore, considering that irbesartan is currently used to treat hypertension combined with type 2 diabetes, we believe that irbesartan should be a suitable choice for patients with both hypertension and hyperlipidemia.

Functional genome annotation and transcriptome analysis of Pseudozyma hubeiensis BOT-O, an oleaginous yeast that utilizes glucose and xylose at equal rates

Pseudozyma hubeiensis is a basidiomycete yeast that has the highly desirable traits for lignocellulose valorisation of being equally efficient at utilization of glucose and xylose, and capable of their co-utilization. The species has previously mainly been studied for its capacity to produce secreted biosurfactants in the form of mannosylerythritol lipids, but it is also an oleaginous species capable of accumulating high levels of triacylglycerol storage lipids during nutrient starvation. In this study, we aimed to further characterize the oleaginous nature of P. hubeiensis by evaluating metabolism and gene expression responses during storage lipid formation conditions with glucose or xylose as a carbon source.The genome of the recently isolated P. hubeiensis BOT-O strain was sequenced using MinION long-read sequencing and resulted in the most contiguous P. hubeiensis assembly to date with 18.95 Mb in 31 contigs. Using transcriptome data as experimental support, we generated the first mRNA-supported P. hubeiensis genome annotation and identified 6540 genes. 80% of the predicted genes were assigned functional annotations based on protein homology to other yeasts. Based on the annotation, key metabolic pathways in BOT-O were reconstructed, including pathways for storage lipids, mannosylerythritol lipids and xylose assimilation. BOT-O was confirmed to consume glucose and xylose at equal rates, but during mixed glucose-xylose cultivation glucose was found to be taken up faster. Differential expression analysis revealed that only a total of 122 genes were significantly differentially expressed at a cut-off of |log2 fold change| ≥ 2 when comparing cultivation on xylose with glucose, during exponential growth and during nitrogen-starvation. Of these 122 genes, a core-set of 24 genes was identified that were differentially expressed at all time points. Nitrogen-starvation resulted in a larger transcriptional effect, with a total of 1179 genes with significant expression changes at the designated fold change cut-off compared with exponential growth on either glucose or xylose.