Human LDL Research Articles

The correlation between biochemical indicators in COVID-19 patients with and without Diabetes Mellitus in Basra, Iraq.

The coronavirus disease (COVID-19) is an infectious viral illness that leads to the development of acute respiratory syndrome. It exhibits a high level of contagiousness. The aforementioned virus is accountable for an incidence of pneumonia that transpired in early December 2019 in Wuhan, situated in the People's Republic of China. The global pandemic declaration on March 11, 2020, marked a significant turning point in the world's demography, as the virus had tragically claimed the lives of over 5.3 million individuals worldwide. The emergence of the Coronavirus (COVID-19) pandemic has presented an unparalleled catastrophe, resulting in the loss of many lives via several channels including social, psychological, physical, and economic dimensions. The danger associated with the virus originates from its heightened transmissibility and extensive mutational variability, as well as its impact on several bodily systems including the circulatory, neurological, renal, hepatic, nervous, and endocrine systems. The pathogenesis of Coronavirus disease 2019 (COVID-19) is intricate, and its clinical presentation is diverse, exhibiting various imaging findings that vary based on the severity of the illness and its progression through time. A general statistical comparison was made for the biochemical markers in the patients infected with only Coronavirus and patients infected with Coronavirus and complications of diabetes mellitus compared to the control group according to gender, in order to monitor the role of different biomarkers in causing a disease, with an evaluation of the difference in their levels, and the study aimed to investigate biomarkers and study the relationship between these biomarkers for COVID-19 patients with and without Diabetes Mellitus, to provide a dynamic approach to understanding the disease to diagnosis and follow-up, so as to improve the development of patients' treatment. The study performed a representative sample of (238) participants between the ages (25-80) year, of whom (81) were in a healthy control group, (78) were infected only with Coronavirus, (79) were infected with Coronavirus and had complications of diabetes mellitus, who visited Al-Basra Teaching Hospital and Allmwanei Hospital in Al-Basra province between October 2021 and February 2022. The age average for the study population was (25-80) years. Serum and blood levels of human CBC, ESR, CRP, Ferritin, D-Dimer, IL 6, Albumin, FBS, HbA1c, Troponin, Cholesterol, Triglyceride, HDL, LDL, VLDL, Creatinine, Urea, Uric acid and GFR were measured. The results show a highly significant increase in WBcs, ESR, CRP, Ferritin, D-Dimer, IL-6, Creatinine, Urea and Uric acid. , and a highly significant decrease in lymphocyte, albumin, HDL and GFR for patients compared to the control group as a total number and the number of males and females separately, While the results of comparing biochemical markers in the patients infected with Coronavirus and who had a diabetic complication a higher significant increase than patients without diabetic complication. The study of these biomarkers provides a dynamic approach to understanding the disease to diagnosis and follow-up, so as to improve the development of patients' treatment and study the relationship between these biomarkers for COVID-19 patients with and without Diabetes Mellitus.

Bioactive compounds from the leaves of Maytenus ilicifolia Mart. ex Reissek: Inhibition of LDL oxidation, glycation, lipid peroxidation, target enzymes, and microbial growth

Ethnopharmacological relevanceMaytenus ilicifolia Mart. ex Reissek, a medicinal plant used for treating gastritis, ulcers, and gastric disorders, possesses therapeutic properties attributed to diverse leaf compounds—terpenoids, alkaloids, flavonoids, phenols, and tannins, reflecting the ethnopharmacological knowledge of traditional users. Aims of the studyWe aimed to assess the antioxidant and antiglycant capacities of Maytenus ilicifolia's ethanolic extract and organic fractions, identify bioactive compounds through HPLC-MS/MS analysis, and conduct phytochemical assessments. We also assessed their potential to inhibit digestive and cholinesterase enzymes, mitigate oxidation of human LDL and rat hepatic tissue, and examine their antimicrobial and cytotoxic properties. Materials and methodsOrganic fractions (hexane - HF-Mi, dichloromethane - DMF-Mi, ethyl acetate - EAF-Mi, n-butanol - BF-Mi, and hydromethanolic - HMF-Mi) were obtained via liquid-liquid partitioning. Antioxidant (DPPH, FRAP, ORAC) and antiglycant (BSA/FRU, BSA/MGO, ARG/MGO/LDL/MGO models) capacities were tested. Phytochemical analysis employed HPLC-MS/MS. We also studied the inhibitory effects on α-amylase, acetylcholinesterase, butyrylcholinesterase, human LDL and rat hepatic tissue oxidation, antimicrobial activity, and cytotoxicity against RAW 264.7 macrophages. ResultsHPLC-ESI-MS/MS identified antioxidant compounds such as catechin, quercetin, and kaempferol derivatives. Ethanolic extract (EE-Mi) and organic fractions demonstrated robust antioxidant and antiglycant activity. EAF-Mi and BF-Mi inhibited α-amylase (2.42 μg/mL and 7.95 μg/mL) compared to acarbose (0.144 μg/mL). Most organic fractions exhibited ∼50% inhibition of acetylcholinesterase and butyrylcholinesterase, rivaling galantamine and rivastigmine. EAF-Mi, BF-Mi, and EE-Mi excelled in inhibiting lipid peroxidation. All fractions, except HMF-Mi, effectively countered LDL oxidation, evidenced by the area under the curve. These fractions protected LDL against lipid peroxidation. ConclusionThis study unveils Maytenus ilicifolia's ethanolic extract and organic fractions properties. Through rigorous analysis, we identify bioactive compounds and highlight their antioxidant, antiglycant, enzyme inhibition, and protective properties against oxidative damage. These findings underline its significance in modern pharmacology and its potential applications in healthcare.

The Study of Biomarkers inSmokers Infected with Covid-19 in Basra, Iraq

Background: The COVID-19 pandemic has heightened awareness of infectious illnesses and their links to host variables and underlying disorders. Objectives: In this review, we look at current research on a possible link between smoking and COVID-19 and study the biomarker changes in patients. Material and Methods: A case-control study included 45 smoker’s patients with COVID-19 and 50 healthy subjects as a control group who visited Al-Basra Teaching Hospital and Allmwanei Hospital in Al-Basra province between October 2021 and February 2022. The age average for the study population was (25-80) years. Serum and blood levels of human CBC, ESR, CRP, Ferritin, D-Dimer, IL 6, Albumin, FBS, HbA1c, Troponin, Cholesterol, Triglyceride, HDL, LDL, VLDL, Creatinine, Urea, Uric acid and GFR were measured. Results: The results show all biomarkers tend to have high sensitivity and specificity for smoker COVID patients based on the ROC curve analysis: Lymphocyte, CRP, Ferritin, D-Dimer, IL 6, Albumin, FBS, HDL, Creatinine, Urea, and GFR. These biomarkers might be helpful in determining the kind and severity of COVID-19 in smokers. Although the data is limited to a total number of patients. Conclusion: Studying patient alterations and vital signs led to the conclusion that smoking and COVID-19 are related. It was also verified that all vital indicators had strong sensitivity and specificity for smoking COVID patients.

SPECT/CT imaging for tracking subendothelial retention of electronegative low-density lipoprotein in vivo

The fifth subfraction of low-density lipoprotein (L5 LDL) can be separated from human LDL using fast-protein liquid chromatography with an anion exchange column. L5 LDL induces vascular endothelial injury both in vitro and in vivo through the lectin-like oxidized LDL receptor-1 (LOX-1). However, no in vivo evidence shows the tendency of L5 LDL deposition on vascular endothelium and links to dysfunction. This study aimed to investigate L5 LDL retention in vivo using SPECT/CT imaging, with Iodine-131 (131I)-labeled and injected into six-month-old apolipoprotein E knockout (apoE−/−) mice through tail veins. Besides, we examined the biodistribution of L5 LDL in tissues and analyzed the intracellular trafficking in human aortic endothelial cells (HAoECs) by confocal microscopy. The impacts of L5 LDL on HAoECs were analyzed using electron microscopy for mitochondrial morphology and western blotting for signaling. Results showed 131I-labeled-L5 was preferentially deposited in the heart and vessels compared to L1 LDL. Furthermore, L5 LDL was co-localized with the mitochondria and associated with mitofusin (MFN1/2) and optic atrophy protein 1 (OPA1) downregulation, leading to mitochondrial fission. In summary, L5 LDL exhibits a propensity for subendothelial retention, thereby promoting endothelial dysfunction and the formation of atherosclerotic lesions.

Schisanhenol ameliorates oxLDL-caused endothelial dysfunction by inhibiting LOX-1 signaling.

Atherosclerotic lesions play a critical role in leading cardiovascular diseases. Oxidized low-density lipoprotein (OxLDL) is a vital risk factor for atherosclerosis since it acts a crucial role in endothelial dysfunction and foam cell formation. Schisanhenol, a composition extracted from the fruit of Schisandra rubriflora, has been reported to have antioxidative effects on human LDL oxidation. This study investigates whether Schisanhenol protects against oxLDL-mediated endothelial damage by modulating the lectin-like oxLDL receptor-1 (LOX-1)-mediated inflammatory processes. Human umbilical vein endothelial cells (HUVECs) were pre-treated with 10 or 20 μM Schisanhenol for 2 h and then exposed to 150 μg/mL oxLDL. We revealed that Schisanhenol reduced oxLDL-enhanced LOX-1 expression. We also found that oxLDL down-regulated endothelial nitric oxide synthase (eNOS) as well as activated inducible NOS (iNOS), thereby enhancing the generation of nitric oxide (NO). Moreover, oxLDL elevated the expression levels of phosphorylated-p38MAPK, subsequently promoting NF-κB-modulated inflammatory responses. Pretreatment with Schisanhenol exerted significant cytoprotective function in all the above-mentioned detrimental events. Results from this present study reveal that Schisanhenol has a potential therapeutic effect on preventing oxLDL-induced endothelial injuries.

Invited Perspective. Per- and Polyfluoroalkyl Substances, Hepatotoxicity, and Liver Disease: Evidence and Clinical Responses

Background: This perspective concerning hepatoxicity of per- and polyfluoroalkyl substances (PFAS) aims to provide a current understanding of the damage and reasonable clinician responses to the needs of concerned patients and affected communities. Methods: Search strategy included PFAS and the following: human liver toxicity/disease; relevant biomarkers including transaminases, lipids, uric acid; predictive equations (for liver disease), liver imaging modalities, and histologic findings. Experimental data concerning liver outcomes and disrupted hepatic metabolic pathways was also reviewed. Recommended clinical approaches to patients and communities was sought in both the National Library of Medicine and relevant organizational websites. Results: Several PFAS reliably cause adverse changes in human liver biomarkers, with strong consistency between human and experimental data. Adverse population changes include human transaminases, cholesterol and LDL cholesterol, and uric acid. This biomarker triad suggests that mechanisms and outcomes are or resemble metabolic associated steatotic liver disease, which is found across species following experimental PFAS exposure. Human imaging studies and sparse human histologic studies mostly support the inference that the toxicant damage is or resembles a pathway that can lead from steatosis to more serious stages of liver disease due to disrupted liver metabolism of fatty acids. Advice to patients and clinicians was reviewed from various agencies and nonprofits organizations including a committee of the US National Academies of Sciences, Engineering, and Medicine, and the nonprofit/university collaboration PFAS REACH. Discussion: Converging lines of evidence indict PFAS as human (and trans-species) hepatotoxins and mostly support a metabolic associated steatotic liver disease continuum as the nature of the injury. Increases in abnormal transaminases and sparser imaging and biopsy findings support that the damage is clinically important and a contributing cause of a public health problem. It is still challenging to decide which of many definitively disrupted metabolic pathways is/are most important to the injury. Many PFAS in use remain virtually unstudied, a research and public health emergency. Simple clinical responses to the concerns of the most heavily contaminated patients and communities, which are within the capabilities of most clinical offices, are reviewed.

Presence of Ceramidase Activity in Electronegative LDL

Electronegative low-density lipoprotein (LDL(-)) is a minor modified fraction of human plasma LDL with several atherogenic properties. Among them is increased bioactive lipid mediator content, such as lysophosphatidylcholine (LPC), non-esterified fatty acids (NEFA), ceramide (Cer), and sphingosine (Sph), which are related to the presence of some phospholipolytic activities, including platelet-activating factor acetylhydrolase (PAF-AH), phospholipase C (PLC), and sphingomyelinase (SMase), in LDL(-). However, these enzymes' activities do not explain the increased Sph content, which typically derives from Cer degradation. In the present study, we analyzed the putative presence of ceramidase (CDase) activity, which could explain the increased Sph content. Thin layer chromatography (TLC) and lipidomic analysis showed that Cer, Sph, and NEFA spontaneously increased in LDL(-) incubated alone at 37 °C, in contrast with native LDL(+). An inhibitor of neutral CDase prevented the formation of Sph and, in turn, increased Cer content in LDL(-). In addition, LDL(-) efficiently degraded fluorescently labeled Cer (NBD-Cer) to form Sph and NEFA. These observations defend the existence of the CDase-like activity's association with LDL(-). However, neither the proteomic analysis nor the Western blot detected the presence of an enzyme with known CDase activity. Further studies are thus warranted to define the origin of the CDase-like activity detected in LDL(-).

Dalcetrapib and anacetrapib increase apolipoprotein E-containing HDL in rabbits and humans

The large HDL particles generated by administration of cholesteryl ester transfer protein inhibitors (CETPi) remain poorly characterized, despite their potential importance in the routing of cholesterol to the liver for excretion, which is the last step of the reverse cholesterol transport. Thus, the effects of the CETPi dalcetrapib and anacetrapib on HDL particle composition were studied in rabbits and humans. The association of rabbit HDL to the LDL receptor (LDLr) in vitro was also evaluated. New Zealand White rabbits receiving atorvastatin were treated with dalcetrapib or anacetrapib. A subset of patients from the dal-PLAQUE-2 study treated with dalcetrapib or placebo were also studied. In rabbits, dalcetrapib and anacetrapib increased HDL-C by more than 58% (P < 0.01) and in turn raised large apo E-containing HDL by 66% (P < 0.001) and 59% (P < 0.01), respectively. Additionally, HDL from CETPi-treated rabbits competed with human LDL for binding to the LDLr on HepG2 cells more than control HDL (P < 0.01). In humans, dalcetrapib increased concentrations of large HDL particles (+69%, P < 0.001) and apo B-depleted plasma apo E (+24%, P < 0.001), leading to the formation of apo E-containing HDL (+47%, P < 0.001) devoid of apo A-I. Overall, in rabbits and humans, CETPi increased large apo E-containing HDL particle concentration, which can interact with hepatic LDLr. The catabolism of these particles may depend on an adequate level of LDLr to contribute to reverse cholesterol transport.

Norbixin, a natural dye that improves serum lipid profile in rabbits and prevents LDL oxidation

We hypothesized that norbixin, which is a carotenoid used as an orange/red natural food coloring additive, has anti-atherogenic properties. An in vitro oxidation assay with human LDL and a rabbit model of atherosclerosis were used to test this hypothesis. Norbixin inhibited the oxidation of isolated human LDL in a concentration-dependent manner. In the in vivo assay, rabbits were fed with a regular chow (control) or an atherogenic diet (0.5% cholesterol) alone or supplemented with norbixin (10, 30 or 100 mg/kg b.w.) for 60 days. Norbixin supplementation (30 and 100 mg/kg b.w.) increased HDL levels and reduced triglyceride levels and the atherogenic index of rabbits. This effect was associated with the decrease of serum levels of oxidized LDL, oxidized LDL antibodies and aortic tissue levels of lipid and protein oxidation in the atherogenic rabbits supplemented with norbixin. Atherogenic diet increased enzymatic (superoxide dismutase, catalase, glutathione reductase, and thioredoxin reductase-1) and non-enzymatic (non-protein thiol groups content) antioxidant defense systems in the aortic tissue but reduced the activity of paraoxonase-1 in the serum. All these changes were prevented by norbixin supplementation (10, 30 and 100 mg/kg b.w.). These results suggest that norbixin has atheroprotective potential by improving serum lipid profile and preventing oxidative modifications of circulating LDL and aortic tissue. Norbixin may, therefore, be beneficial in the control of atherosclerosis risk factors and can be further investigated as a candidate to be used not only as a functional food ingredient but also for therapeutic applications and in the nutraceutical industry.

Larrea divaricata: anti-inflammatory and antioxidant effects on macrophages and low density lipoproteins

BackgroundThe oxidized low density lipoprotein (ox-LDL) contributes to inflammation and oxidative stress through the activation of macrophages under hyperglycemia contributing to the development of diabetes mellitus and to atherosclerosis. Plants are a source of effective and innocuous antioxidants. Larrea divaricata Cav. (Zygophyllaceae) is used in Argentina folk medicine for its anti-inflammatory properties.MethodsThe aim of this work was to study the antioxidant and anti-inflammatory effects of the aqueous extract (AE) of L. divaricata on macrophages under glucose stimulation and on human LDL and HDL particles under free radical generators. ResultsAE reduced the lipid peroxidation (17%), nitric oxide (NO) (47-50%), tumor necrosis factor-α (TNF-α) (32%) and free radicals (50%) induced by glucose on macrophages. Also prevented HDL nitration (28%), thus preserving its function and structure and inhibited LDL oxidation. The effect on the nitrosative stress was mainly driven by nordihydroguaiaretic acid (NDGA).ConclusionsThese results suggest a potential usefulness of AE as an adjuvant phytotherapy in patients with diabetes mellitus and atherosclerosis.

Phytonutrients of Bitter Apricot Seeds Modulate Human Lipid Profile and LDL Subfractions in Adults with Elevated Cholesterol Levels.

The objective of the present study was to evaluate the effect of short-term consumption of bitter apricot seeds phytonutrients on cardiovascular risk factors with a special focus on LDL cholesterol subfractions using the Lipoprint system. A group of 34 adult volunteers (21 female/13 male) consumed 60 mg kg−1 of body weight of bitter apricot seeds daily for 42 days. Subjects were divided into two groups: one with normal cholesterol levels (NTC) and one with elevated total cholesterol levels (ETC). Blood serum levels of total cholesterol (T-C), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C), and triglycerides (TG) did not change significantly (p > 0.05) in NTC group. However, there were significant decreasing of T-C (p ˂ 0.05) and LDL-C (p < 0.01) in ETC group. The LDL1, LDL2, and atherogenic LDL3−7 subfractions progressively decreased after 42 days of apricot seeds consumption in ETC group (p < 0.05). Apricot seeds consumption was associated with a significant increase in the mean LDL particle size especially in ETC group (p ˂ 0.01). The results of the present study support the hypothesis that daily consumption of bitter apricot seeds for 42 days positively modified the lipoprotein profile in the group with elevated total cholesterol.

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Meet the First Authors.

Assessment of Ex Vivo Antioxidative Potential of Murine HDL in Atherosclerosis.

This chapter provides details on a simple and reproducible method used to determine the capacity of murine HDL to prevent the oxidation of LDL . The principle of the method is based on the rearrangement of double bonds of polyunsaturated fatty acids that occurs during the oxidation of human LDL , which generates a sigmoidal curve. The shape and length of the curve is modified in the presence of HDL , and such modifications are easily quantifiable by measuring the absorbance of conjugated dienes at 234nm. The general technique described herein may be applied to evaluate the effect of HDL obtained from different experimental murine models of atherosclerosis.

Posttranscriptional Regulation of the Human LDL Receptor by the U2-Spliceosome

The LDLR (low-density lipoprotein receptor) in the liver is the major determinant of LDL-cholesterol levels in human plasma. The discovery of genes that regulate the activity of LDLR helps to identify pathomechanisms of hypercholesterolemia and novel therapeutic targets against atherosclerotic cardiovascular disease. We performed a genome-wide RNA interference screen for genes limiting the uptake of fluorescent LDL into Huh-7 hepatocarcinoma cells. Top hit genes were validated by in vitro experiments as well as analyses of data sets on gene expression and variants in human populations. The knockdown of 54 genes significantly inhibited LDL uptake. Fifteen of them encode for components or interactors of the U2-spliceosome. Knocking down any one of 11 out of 15 genes resulted in the selective retention of intron 3 of LDLR. The translated LDLR fragment lacks 88% of the full length LDLR and is detectable neither in nontransfected cells nor in human plasma. The hepatic expression of the intron 3 retention transcript is increased in nonalcoholic fatty liver disease as well as after bariatric surgery. Its expression in blood cells correlates with LDL-cholesterol and age. Single nucleotide polymorphisms and 3 rare variants of one spliceosome gene, RBM25, are associated with LDL-cholesterol in the population and familial hypercholesterolemia, respectively. Compared with overexpression of wild-type RBM25, overexpression of the 3 rare RBM25 mutants in Huh-7 cells led to lower LDL uptake. We identified a novel mechanism of posttranscriptional regulation of LDLR activity in humans and associations of genetic variants of RBM25 with LDL-cholesterol levels.

Cellulolytic and xylanolytic enzyme combinations in the hydrolysis of red rice bran: A disparity in the release of nutraceuticals and its correlation with bioactivities

Multienzyme-aided processing is recommended as an effective method for releasing the bioactive compounds bounded to rice bran's cell wall matrix. This study aims to investigate the optimal cellulolytic-xylanolytic enzymes combination (CXC1 = 1.5 + 3 units, CXC2 = 3 + 2 units, CXC3 = 4.5 + 1 units per 2 g bran) for improving the release of nutraceuticals and bioactivities from red rice bran compared to control. The results showed significant (p ≤ 0.05) synergistic activities at CXC2 combination with the highest increase in ferulic acid (253%) in soluble phenolics, p-coumaric acid (66%) in bound phenolics and γ-oryzanol fractions (41%–743%). Bioactivity assays showed that all three enzyme combinations exhibited higher ferric reducing power (∼71%), DPPH• (∼13%), nitric oxide (∼114%) scavenging and inhibition of human LDL oxidation (∼13%–34%). While CXC1 and CXC2 increased superoxide anion (∼153%) and hydroxyl radical (∼44%) scavenging activities. Correlation study showed soluble phenolics, ferulic, caffeic acid and 24-methylenecycloartanyl ferulate, exhibiting positive correlation while protocatechuic acid and γ-tocopherol negative correlation with bioactivities. Thus, applying an optimal cellulolytic-xylanolytic enzyme combination is a potential approach for processing the rice bran into a functional food ingredient.

In vitro antioxidant activity of meniran (Phyllantus urinaria) functional drink in human low density lipoprotein (LDL)

Preparation process for meniran (Phillantus urinaria) functional drink (MFD) influences its antioxidant activity. This research aims to understand the phenolic content, DPPH Radical Scavenging Activity (RSA), and LDL oxidation of MFD through various preparation processes. Those preparation processes included soaking fresh meniran (SFM), boiling fresh meniran for 5 minutes (BFM5’), boiling fresh meniran for 10 minutes (BFM10’), and soaking dried meniran (DM). The phenolic content was determined with Folin–Ciocalteu, antioxidant activity was assessed using DPPH and TBARS assay with LDL as the oxidation substrate. An antioxidant references in this research used ascorbic acid. The phenolic content in methods of SFM, BFM5’, BFM10’ and DM were 122±0.022, 182±0.043, 192 ±0.03, and 117 ±0.019 mg GAE/g of meniran respectively. Meanwhile, the DPPH RSA of SFM, BFM5’, BFM10’ and DM accounted for 82.18±0.35, 86.19±0.53, 86.75±0.64 and 69.96% respectively. As comparison, the DPPH RSA of ascorbic acid 50 ppm is 75.65±0.82%. At the same time the optimum inhibition of TBARS formation from BFM5’ and BFM10’ methods were 45.83 % and 48.66%, with MDA concentration in human LDL accounted for 38.30±2.39 and 36.30±1.82 nmol MDA/mg protein, respectively. As comparison, MDA concentration in human LDL added with ascorbic acid 25 ppm accounted for 41.35±2.41 nmol MDA/mg protein. In contrast, the control human LDL was 70.70±2.35 nmol MDA/mg protein. This study concludes that the BFM5’ and BFM10’ methods showed the highest antioxidant properties compared to other methods. All methods showed that MFD extract in concentration more than 25 ppm increased the concentration of MDA in human LDL. Therefore, to produce meniran functional drink in optimum antioxidant properties is best by using BFM5’ and BFM10’ preparation methods in meniran concentration of not more than 25 ppm.

Hydrolysis of glycerophosphocholine epoxides by human group IIA, V, and X secretory phospholipases A2.

This study was prompted by recent reports that epoxyeicosatrienoic (EET) and epoxyeicosatetraenoic (EEQ) acids accelerate tumor growth and metastasis by stimulation of angiogenesis, while eicosapentaenoic (EPA) and epoxydocosapentaenoic (EDP) acids inhibit angiogenesis, tumor growth, and metastasis. Cytochrome P450 epoxygenases convert arachidonic to EET, eicosapentaenoic acid to EEQ, and docosahexaenoic acid to EDP, which are found both in free form and esterified to glycerophosphocholine (GPC). Both free and esterified epoxy (EP) acids are also formed during lipid autoxidation. For biological activity, the GPC-EP requires hydrolysis, which we presumed could occur by sPLA2 s located in proximity of lipoproteins carrying the lipid epoxides. The plasma lipoproteins were isolated by ultracentrifugation and analyzed by LC/ESI-MS. The GPC-EPs were identified by reference to standards and to retention times of phospholipid masses. The GPC-EP monoepoxides (corrected for isobaric ether overlaps) in stored human LDL, HDL, HDL3 , or APHDL ranged from 0 to 1 nmol/mg protein, but during 4-h incubation at 37°C increased to 1-5 nmol/mg protein. An incubation of autoxidized LDL, HDL, or HDL3 with 1 μg/ml of group V or X sPLA2 resulted in complete hydrolysis of diacyl GPC epoxide esters. Group IIA sPLA2 at 1 μg/ml failed to produce significant hydrolysis in 4 h, but at 2.5 μg/ml in 8 h yielded almost 80% hydrolysis, which represented complete diacyl GPC-EP hydrolysis. The present study shows that group IIA, V, and X sPLA2 s are capable of extensive hydrolysis of PtdCho epoxides of autoxidized plasma lipoproteins. Therefore, all three human sPLA2 s were potentially capable of inducing epoxide biological activity in vivo.

Ellagitannins from jabuticaba (Myrciaria jaboticaba) seeds attenuated inflammation, oxidative stress, aberrant crypt foci, and modulated gut microbiota in rats with 1,2 dimethyl hydrazine-induced colon carcinogenesis

Since dietary factors are thought to be responsible for high colon cancer risk, we investigated the chemopreventive effect of jabuticaba seed extract (LJE) by administering yogurt with or without LJE against 1,2 dimethyl hydrazine (DMH)-induced colon carcinogenesis in rats. Results showed that LJE contained a total phenolic content of 57.16 g/100 g of seed extract in which 7.67 and 10.09 g/100 g represented total flavonoids and ellagitannins, respectively. LJE protected DNA and human LDL against induced in vitro oxidation, which was associated with the ellagitannin content and with the free-radical scavenging and reducing capacities. LJE alone had a non-clastogenicity/aneugenicity property, but in combination with cisplatin, it enhanced the chromosome aberrations in cancer cells. In colon cancer-induced rats, yogurt with or without LJE caused a reduction in pro-inflammatory parameters, decreased the RNA expression of antiapoptotic cytokines and increased the expression of proapoptotic cytokines. Moreover, LJE attenuated colon cancer initiation and progression by decreasing aberrant crypt foci and LJE recovered the gut microbiome. Together, this evidence suggests that LJE provides chemopreventive protection against colon cancer development by reducing inflammation and increasing proapoptotic pathways.

Role of endoxylanase and its concentrations in enhancing the nutraceutical components and bioactivities of red rice bran

Enzyme type and concentration are crucial factors in improving the release of bioactive compounds entrapped in rice bran's complex cell wall matrix. This work investigates the effect of various concentrations (2–20-units/2 g) of endoxylanase from bacterial (EXB) and fungal (EXF) origin in enhancing the content of phenolics, tocopherols, tocotrienols, and γ-oryzanol, and boosting the bioactivities of red rice bran compared to non-enzyme treated bran (control). At specific concentrations, EXF increased caffeic (503%) vanillic (354%) and ferulic acid (186%) in soluble phenolics, along with cycloartenyl ferulate (35%), β-sitosteryl ferulate (33%) and δ, γ, α-tocopherols (24%–210%) and tocotrienols (50%–182%). Whereas EXB enhanced catechin (267%) and p-coumaric acid (269%) in bound phenolics along with 24-methylenecycloartenyl ferulate (48%) and campesteryl ferulate (97%). The bioactivity assays and correlation study showed that EXF treated bran exhibited scavenging activities against, superoxide anion (76%), and inhibition of human LDL oxidation (93%) with caffeic acid and α-tocotrienol exhibiting positive correlation. While EXB treated bran exhibited reducing power (109%), DPPH• (60%), and hydroxyl (25%) radical scavenging activities, with β-sitosteryl ferulate, and soluble phenolics demonstrating positive correlation. Thus, endoxylanase treatment is a potential approach for processing the rice bran into a functional food ingredient having higher bioactivities.

Citrullinated and homocitrullinated low- density lipoprotein in rheumatoid arthritis

Objective: Antibodies to citrullinated and homocitrullinated (also known as carbamylated) proteins, specific for rheumatoid arthritis (RA), are associated with cardiovascular disease (CVD). Immune complexes containing these proteins have been identified in the atherosclerotic plaque of CVD patients. In mice, homocitrullinated low-density lipoprotein (HomoCitLDL) promotes foam cell formation, which is critical in the pathogenesis of atherosclerosis. We aimed to investigate the atherogenic potential of HomoCitLDL and citrullinated low-density lipoprotein (CitLDL) in RA. Method: Human LDL was homocitrullinated in potassium cyanate and citrullinated by rabbit skeletal muscle peptidyl arginine deiminase-2. The modifications were confirmed by mass spectrometry. Primary human monoctyes from healthy subjects (N = 8) were differentiated to macrophages using macrophage colony-stimulating factor and incubated with modified LDL. Foam cells were visualized using Oil Red O staining. Serum from RA patients (N = 101) and controls (N = 32) was tested for immunoglobulin G antibodies to modified LDL using enzyme-linked immunosorbent assay. Results: HomoCitLDL and CitLDL strongly induced foam cell production (> 90%) versus unmodified LDL (11%) (p < 0.0001). The characteristics of the RA subjects were: 73% females, median age 60 [interquartile range (IQR) 17] years and disease duration 7.5 (IQR 13) years; 11% had a prior major cardiovascular event, 66% were ever smokers, 32% had hypertension, 33% dyslipidaemia, and 14% diabetes. Antibodies to HomoCitLDL were detected in 18% of RA patients; they were significantly associated with dyslipidaemia [odds ratio (OR) 3.86; 95% confidence interval (CI) 1.22, 12.17] and antibodies to other homocitrullinated antigens (OR 10.61; 95% CI 1.31, 86.11). Conclusions: HomoCitLDL and CitLDL have atherogenic properties in vitro. Antibody responses to HomoCitLDL, but not CitLDL, were detected in RA patients.