Levels Of Apolipoprotein Research Articles

Hubungan Rasio APO-B/APOA-I dengan Index Massa Tubuh

Body Mass Index (BMI) is a simple way to monitor weight. Overweight as a result of excessive body fat accumulation which is characterized by a decrease in HDL (High-Density Lipoprotein), namely the atherogenic side represented by levels of Apolipoprotein AI (ApoA-I), increased triglycerides (TG), VLDL (Very Low-Density Lipoprotein). ), LDL (Low-Density Lipoprotein), and Total Cholesterol which is the anti-atherogenic side represented by the levels of Apolipoprotein B (Apo-B). If we measure both Apo-B and ApoA-I and express them as the Apo-B/ApoA-I ratio, we get a strong marker of cardiovascular risk. By combining the two markers in the ratio, we get synergies and increase predictive power. This study aims to analyze the levels of Apo-B, ApoA-I, and the ratio of Apo-B/ApoA-I to BMI. An experimental study with a cross-sectional design using 72 subjects during April 2021. Apo-B and ApoA-I were examined using the Cobas c311/501 instrument with the immunoturbidimetric test method. The results of this study showed a significant relationship between Apo-B levels and BMI, while ApoA-I levels and Apo-B/ApoA-I ratios did not have a significant relationship. In conclusion, there is no relationship between BMI and the ApoB/ApoA-I ratio in male and female subjects.

Effect of L-Glutamine on Chylomicron Formation and Fat-Induced Activation of Intestinal Mucosal Mast Cells in Sprague-Dawley Rats.

Glutamine (Gln) is required for intestinal mucosal homeostasis, and it can promote triglyceride absorption. The intestinal mucosal mast cells (MMCs) are activated during fat absorption. This study investigated the potential role of Gln on fat absorption-induced activation of MMCs in rats. Lymph fistula rats (n = 24) were studied after an overnight recovery with the infusion of saline only, saline plus 85 mM L-glutamine (L-Gln) or 85 mM D-glutamine (D-Gln), respectively. On the test day, rats (n = 8/group) were given an intraduodenal bolus of 20% Intralipid contained either saline only (vehicle group), 85 mM L-Gln (L-Gln group), or 85 mM D-Gln (D-Gln group). Lymph was collected hourly for up to 6 h for analyses. The results showed that intestinal lymph from rats given L-Gln had increased levels of apolipoprotein B (ApoB) and A-I (ApoA-I), concomitant with an increased spectrum of smaller chylomicron particles. Unexpectedly, L-Gln also increased levels of rat mucosal mast cell protease II (RMCPII), as well as histamine and prostaglandin D2 (PGD2) in response to dietary lipid. However, these effects were not observed in rats treated with 85 mM of the stereoisomer D-Gln. Our results showed that L-glutamine could specifically activate MMCs to degranulate and release MMC mediators to the lymph during fat absorption. This observation is potentially important clinically since L-glutamine is often used to promote gut health and repair leaky gut.

Hydroalcoholic extract of dill and aerobic training prevents high-fat diet-induced metabolic risk factors by improving miR-33 and miR-223 expression in rat liver.

Exercise training and medicinal herb supplementation may improve microRNAs (miRNAs) expression associated with obesity. This study aimed to assess the effects of 10 weeks of aerobic training (AT) and dill extract (DE) on miR-33 and miR-223 expression of liver in high-fat diet (HFD)-induced obese rats. Forty male Wistar rats were fed a defined high-fat (n=32) and standard (n=8, nonobese control [NC]) diet. After obesity induction, obese rats were randomly allocated to four groups: AT, DE, AT + DE, and obese control (OC). Rats were euthanized and plasma and liver tissue samples were collected after the intervention. The liver expression of miR-33 was lower in the AT, DE, AT + DE, and NC groups compared with the OC group. Also, the liver miR-223 expression was higher in the AT, DE, AT + DE, and NC groups compared with the OC group. Moreover, the liver expression of miR-223 in the AT + DE group was higher compared with the AT and DE groups. The AT, DE, AT + DE, and NC groups had lower liver TC compared with the OC group. Also, the plasma level of apolipoprotein B (Apo B) was significantly lower, and liver HDL-C was significantly higher in the AT + DE and NC groups compared with the OC group. These findings show that long-term AT combined with the intake of DE may improve the plasma levels of Apo B, and TC and HDL-C levels in the liver, which is probably due to AT and DE positive effects on miR-33 and miR-223 in the liver of obese rats. PRACTICAL APPLICATIONS: Aerobic training reduces overweight and obesity health problems, however, the duration and intensity of the exercise training distinguish between individuals. We used an integrated approach combining pharmacological and non-pharmacological as a medical strategy to prevent HFD-induced metabolic injury in obese rats. The present results discovered that a combination of AT + DE intervention improves the miR-33 and miR-223 in the liver of obese rats.

Causal Association of Type 2 Diabetes Mellitus and Glycemic Traits With Cardiovascular Diseases and Lipid Traits: A Mendelian Randomization Study.

ObjectiveWe aimed to evaluate the causal effect of type 2 diabetes mellitus (T2DM) and glycemic traits on the risk of a wide range of cardiovascular diseases (CVDs) and lipid traits using Mendelian randomization (MR).MethodsGenetic variants associated with T2DM, fasting glucose, fasting insulin, and hemoglobin A1c were selected as instrumental variables to perform both univariable and multivariable MR analyses.ResultsIn univariable MR, genetically predicted T2DM was associated with higher odds of peripheral artery disease (pooled odds ratio (OR) =1.207, 95% CI: 1.162-1.254), myocardial infarction (OR =1.132, 95% CI: 1.104-1.160), ischemic heart disease (OR =1.129, 95% CI: 1.105-1.154), heart failure (OR =1.050, 95% CI: 1.029-1.072), stroke (OR =1.087, 95% CI: 1.068-1.107), ischemic stroke (OR =1.080, 95% CI: 1.059-1.102), essential hypertension (OR =1.013, 95% CI: 1.010-1.015), coronary atherosclerosis (OR =1.005, 95% CI: 1.004-1.007), and major coronary heart disease event (OR =1.003, 95% CI: 1.002-1.004). Additionally, T2DM was causally related to lower levels of high-density lipoprotein cholesterol (OR =0.965, 95% CI: 0.958-0.973) and apolipoprotein A (OR =0.982, 95% CI: 0.977-0.987) but a higher level of triglycerides (OR =1.060, 95% CI: 1.036-1.084). Moreover, causal effect of glycemic traits on CVDs and lipid traits were also observed. Finally, most results of univariable MR were supported by multivariable MR.ConclusionWe provided evidence for the causal effects of T2DM and glycemic traits on the risk of CVDs and dyslipidemia. Further investigations to elucidate the underlying mechanisms are warranted.

Association of plasma apolipoproteins and levels of inflammation-related factors with different stages of Alzheimer’s disease: a cross-sectional study

ObjectiveBlood-based biomarkers for the early diagnosis of Alzheimer’s disease (AD) are a ‘Holy Grail’ of AD research. Growing evidence shows that levels of apolipoproteins and various inflammation-related factors are altered...

Mycobacterium tuberculosis Affects Protein and Lipid Content of Circulating Exosomes in Infected Patients Depending on Tuberculosis Disease State.

Tuberculosis (TB), which is caused by the bacterium Mycobacterium tuberculosis (Mtb), is still one of the deadliest infectious diseases. Understanding how the host and pathogen interact in active TB will have a significant impact on global TB control efforts. Exosomes are increasingly recognized as a means of cell-to-cell contact and exchange of soluble mediators. In the case of TB, exosomes are released from the bacillus and infected cells. In the present study, a comprehensive lipidomics and proteomics analysis of size exclusion chromatography-isolated plasma-derived exosomes from patients with TB lymphadenitis (TBL) and treated as well as untreated pulmonary TB (PTB) was performed to elucidate the possibility to utilize exosomes in diagnostics and knowledge building. According to our findings, exosome-derived lipids and proteins originate from both the host and Mtb in the plasma of active TB patients. Exosomes from all patients are mostly composed of sphingomyelins (SM), phosphatidylcholines, phosphatidylinositols, free fatty acids, triacylglycerols (TAG), and cholesterylesters. Relative proportions of, e.g., SMs and TAGs, vary depending on the disease or treatment state and could be linked to Mtb pathogenesis and dormancy. We identified three proteins of Mtb origin: DNA-directed RNA polymerase subunit beta (RpoC), Diacyglycerol O-acyltransferase (Rv2285), and Formate hydrogenase (HycE), the latter of which was discovered to be differently expressed in TBL patients. Furthermore, we discovered that Mtb infection alters the host protein composition of circulating exosomes, significantly affecting a total of 37 proteins. All TB patients had low levels of apolipoproteins, as well as the antibacterial proteins cathelicidin, Scavenger Receptor Cysteine Rich Family Member (SSC5D), and Ficolin 3 (FCN3). When compared to healthy controls, the protein profiles of PTB and TBL were substantially linked, with 14 proteins being co-regulated. However, adhesion proteins (integrins, Intercellular adhesion molecule 2 (ICAM2), CD151, Proteoglycan 4 (PRG4)) were shown to be more prevalent in PTB patients, while immunoglobulins, Complement component 1r (C1R), and Glutamate receptor-interacting protein 1 (GRIP1) were found to be more abundant in TBL patients, respectively. This study could confirm findings from previous reports and uncover novel molecular profiles not previously in focus of TB research. However, we applied a minimally invasive sampling and analysis of circulating exosomes in TB patients. Based on the findings given here, future studies into host–pathogen interactions could pave the way for the development of new vaccines and therapies.

Thioredoxin Domain Containing 5 Suppression Elicits Serum Amyloid A-Containing High-Density Lipoproteins.

Thioredoxin domain containing 5 (TXNDC5) is a protein disulfide isomerase involved in several diseases related to oxidative stress, energy metabolism and cellular inflammation. In a previous manuscript, a negative association between fatty liver development and hepatic Txndc5 expression was observed. To study the role of TXNDC5 in the liver, we generated Txndc5-deficient mice. The absence of the protein caused an increased metabolic need to gain weight along with a bigger and fatter liver. RNAseq was performed to elucidate the putative mechanisms, showing a substantial liver overexpression of serum amyloid genes (Saa1, Saa2) with no changes in hepatic protein, but discrete plasma augmentation by the gene inactivation. Higher levels of malonyldialdehyde, apolipoprotein A1 and platelet activating factor-aryl esterase activity were also found in serum from Txndc5-deficient mice. However, no difference in the distribution of high-density lipoproteins (HDL)-mayor components and SAA was found between groups, and even the reactive oxygen species decreased in HDL coming from Txndc5-deficient mice. These results confirm the relation of this gene with hepatic steatosis and with a fasting metabolic derive remedying an acute phase response. Likewise, they pose a new role in modulating the nature of HDL particles, and SAA-containing HDL particles are not particularly oxidized.

Sortilin restricts secretion of apolipoprotein B-100 by hepatocytes under stressed but not basal conditions.

Genetic variants at the SORT1 locus in humans, which cause increased SORT1 expression in the liver, are significantly associated with reduced plasma levels of LDL cholesterol and apolipoprotein B (apoB). However, the role of hepatic sortilin remains controversial, as genetic deletion of sortilin in mice has resulted in variable and conflicting effects on apoB secretion. Here, we found that Sort1-KO mice on a chow diet and several Sort1-deficient hepatocyte lines displayed no difference in apoB secretion. When these models were challenged with high-fat diet or ER stress, the loss of Sort1 expression resulted in a significant increase in apoB-100 secretion. Sort1-overexpression studies yielded reciprocal results. Importantly, carriers of SORT1 variant with diabetes had larger decreases in plasma apoB, TG, and VLDL and LDL particle number as compared with people without diabetes with the same variants. We conclude that, under basal nonstressed conditions, loss of sortilin has little effect on hepatocyte apoB secretion, whereas, in the setting of lipid loading or ER stress, sortilin deficiency leads to increased apoB secretion. These results are consistent with the directionality of effect in human genetics studies and suggest that, under stress conditions, hepatic sortilin directs apoB toward lysosomal degradation rather than secretion, potentially serving as a quality control step in the apoB secretion pathway in hepatocytes.

Plasma ApoB/AI: An effective indicator for intracranial vascular positive remodeling

ObjectivesBoth vascular positive remodeling and apolipoprotein B/apolipoprotein AI (apoB/AI) are important risk factors for ischemic stroke. However, it is unclear whether apoB/AI level plays a role in vascular positive remodeling. This study aimed to investigate the association between apoB/AI and intracranial vascular positive remodeling. Materials and methodsSymptomatic patients with intracranial artery 30–99% stenosis were recruited and underwent high-resolution magnetic resonance (MR) imaging. The levels of apolipoprotein B (apoB), apolipoprotein AI (apoAI) and apoB/AI were tested. Intracranial vascular remodeling index (RI) defined as the wall area ratio between maximal luminal narrowing and reference site was evaluated on MR images. Positive remodeling was defined as RI ≥1.05. The association between apoB/AI level and positive remodeling was respectively determined in anterior and posterior circulation. ResultsOf 65 recruited patients (mean age: 58.5 ± 10.6 years; 36 males), 25 (38.5%) had positive remodeling, of which 24 (36.9%) were in the posterior circulation group. Patients with positive remodeling had significantly higher apoB (1.0 ± 0.3 g/L vs. 0.8 ± 0.3 g/L, P = 0.003) and apoB/AI (1.0 ± 0.3 vs. 0.8 ± 0.2, P = 0.008) than those without. Univariate logistic regression showed that apoB/AI (OR: 2.302, 95%CI: 1.229–4.321, P = 0.009) was significantly associated with positive remodeling. After adjusted for confounders, the association of apoB/AI (OR: 2.935, 95%CI: 1.061–8.123, P = 0.038) with positive remodeling remained significant. ApoB/AI (OR: 76.110, 95%CI: 1.169–4953.287, P = 0.042) was significantly associated with positive remodeling in posterior circulation but not in anterior circulation. ConclusionApoB/AI is a potential indicator for intracranial vulnerable atherosclerosis characterized by positive remodeling, especially in posterior circulation.

Probiotic kefir consumption improves serum apolipoprotein A1 levels in metabolic syndrome patients: a randomized controlled clinical trial

Metabolic syndrome has become a major health hazard of the modern world. Studies investigating the effects of traditional fermented foods on metabolic syndrome are limited. We hypothesized that regular kefir consumption could improve the anthropometrical measurements, glycemic control, lipid profile, blood pressure, and inflammatory status in patients with metabolic syndrome. Sixty-two participants were randomly assigned to receive either 180 mL/d probiotic kefir or unfermented milk for 12 weeks. Dietary intake, anthropometrical measurements, biochemical status, and blood pressure were assessed at baseline and the end of weeks 4, 8, and 12. Serum apolipoprotein A1 concentration increased by 3.4% in the kefir group, whereas it decreased by 2.4% in the milk group in 12 weeks (P=.03). A subgroup analysis for participants with low-density lipoprotein cholesterol (LDL-C) levels >130 mg/dL showed that serum LDL-C and apolipoprotein B concentrations (7.6% and 5.4%, respectively) significantly decreased with kefir consumption compared with the baseline values at the 12th week (P < .05), but not compared with milk consumption (P > .05). Both milk and kefir consumption was associated with lower systolic and diastolic blood pressure compared with the baseline (P < .05). The 12-weeks of kefir administration also decreased serum tumor necrosis factor-α, interleukin 6, interleukin 10, interferon-gamma, and homocysteine concentrations significantly (P < .05). In conclusion, regular dairy consumption as part of a well-balanced diet can provide favorable effects in the management of metabolic syndrome, and probiotic kefir may deserve a special interest among dairy products. This trial was registered at clinicaltrials.gov (NCT03966846).

Associations of Thyroid Function Tests with Lipid Levels and Adverse Pregnancy Outcomes During the First Trimester.

ObjectiveThe present study aims to evaluate the relationship of thyroid function during the first trimester of pregnancy with lipid levels and pregnancy outcomes.MethodsWomen who delivered babies at the Shanghai General Hospital between March 2019 and December 2019 with a known pregnancy outcome and complete data were included in the present study (n = 1779). A retrospective cohort study of all subjects with available first-trimester thyroid function testing and lipid levels data was conducted, and the relationship of thyroid function with lipid levels and pregnancy outcomes was evaluated. The data were analyzed using the SPSS software for statistical correlation.ResultsThe proportion of caesarean sections was higher in women with hypothyroxinemia (HIA) and hypothyroidism than in women with euthyroidism. Hypothyroidism was shown to be related with polyhydramnios, preterm labor and hypertriglyceridemia. HIA was correlated with increased rates of gestational diabetes mellitus (GDM), preeclampsia, gestational hypertension and hypertriglyceridemia. Compared with the euthyroidism group, the hypothyroidism group had a higher apolipoprotein A1 (Apo A1) level and apolipoprotein B level; the subclinical hypothyroidism group had a higher total cholesterol (TC) level and low-density lipoprotein cholesterol level; the HIA group had higher triglyceride, high-density lipoprotein cholesterol levels and lower TC, Apo A1 levels. TC levels were positively correlated with the thyroid-stimulating hormone level and negatively correlated with free thyroxine (FT4) level, and free triiodothyronine and FT4 levels were positively correlated with GDM occurrence.ConclusionThyroid function in early pregnancy is associated with dyslipidemia and pregnancy outcomes; conventional screening of thyroid diseases in early pregnancy may help improve lipid levels and decrease adverse pregnancy outcomes.

Angiogenin Levels and Their Association with Cardiometabolic Indices Following Vitamin D Status Correction in Saudi Adults.

Simple SummaryAngiogenin (ANG) is a small 123 amino acid protein which in normal growth is associated with formation of new blood vessels in a process called angiogenesis; however, the abnormal levels of this protein in blood has been associated with diseases such as cancer, neurological disorders, and cardiovascular diseases. Vitamin D deficiency and elevated levels of blood lipids have also been associated with many diseases including cardiovascular diseases. In this study, the investigators tried to evaluate the relationship between the circulating levels of ANG, vitamin D, and lipids. The model used was vitamin D supplementation of deficient Saudi adults in order to find the effect of vitamin D correction on circulating levels of ANG and blood lipids. With vitamin D supplementation, modest but non-significant elevation in ANG was observed, as well as significant increase in apolipoproteins CIII and E and significant decrease in apo B. In addition, the correlation between circulating levels of ANG and apolipoproteins especially apo E observed in this study are interesting and should be investigated more as both are linked with neurologic disorders like Alzheimer’s and Parkinson’s diseases.Angiogenin (ANG), a multifunctional protein known to induce blood vessel formation, is a potential biomarker for cardiovascular diseases; however, whether it is affected by vitamin D supplementation is not known. This interventional study in vitamin D-deficient Saudi adults was designed to investigate it. A total of 100 vitamin D-deficient Saudi adults aged 30–50 years were randomly selected to undergo 6-month vitamin D supplementation. Circulating levels of fasting glucose, lipids, vitamin D, apolipoproteins (AI, AII, B, CI, CII, CIII, E, and H), and ANG were measured using commercially available assays at baseline and after six months. Overall, vitamin D levels increased significantly post intervention. With this, levels of apo-CIII and apo-E significantly increased (p-values of 0.001 and 0.009, respectively) with a significant parallel decrease in apo-B (p = 0.003). ANG levels were significantly positively associated with most apolipoproteins and inversely correlated with HDL-cholesterol. Post intervention, the changes in ANG levels were positively correlated with apo-E (r = 0.32; p < 0.01 in all subjects and r = 0.40; p < 0.05 in males). Vitamin D supplementation may modestly affect ANG levels. The association observed between ANG and apo-E is worthy of further investigation since both biomarkers have been linked to neurodegenerative disorders.

Effect of APOE ε4 Allele on Levels of Apolipoproteins E, J, and D, and Redox Signature In Circulating Extracellular Vesicles from Cognitively Impaired with No Dementia Participants Converted to Alzheimer’s Disease

Effect of APOE ε4 Allele on Levels of Apolipoproteins E, J, and D, and Redox Signature In Circulating Extracellular Vesicles from Cognitively Impaired with No Dementia Participants Converted to Alzheimer’s Disease

HDL-Associated Lipoproteins: Potential Prognostic Biomarkers for Gram-Negative Sepsis.

PurposeTo determine the levels of serum HDL-associated apolipoproteins (apoM and apoC) and HDL-binding receptor (scavenger receptor BI, SR-BI) in patients with gram-negative bacteria sepsis (G-sepsis) and to evaluate the value of lipoproteins in the diagnosis, severity and prognosis of G-sepsis.Patients and MethodsA total of 128 patients with sepsis, 40 patients with system inflammatory reaction syndrome (SIRS) and 40 healthy subjects were enrolled in the Second People’s Hospital of Hunan Province from September 2019 to September 2020. The levels and the correlation of lipoproteins were detected and dynamically monitored by enzyme-linked adsorption method, ROC curve for the diagnostic, severity and prognostic value of lipoproteins in G-sepsis.ResultsThe levels of serum HDL-associated lipoproteins in patients with G-sepsis were significantly decreased (P < 0.05), and the ROC curve showed that HDL-C, SR-BI, apoM and apoC had cut-off values of 0.915 mmol/L, 122.100 pg/mL, 102.400 ug/mL and 17.55 mg/mL, respectively, for the diagnosis of G-sepsis, with the sensitivity was 85.56%, 97.78%, 93.33% and 73.03%, and the specificity was 95.0%, 82.50%, 61.54% and 82.50%, respectively. There was a correlation between HDL-associated apolipoproteins. Changes in serum HDL-associated lipoproteins were more obvious in shock group than classic inflammation indicators, such as PCT, IL-6 and CRP. They showed a trend change on day 3, with the levels of SR-BI and apoC changing 2–3 times, and the sensitivity of HDL-C, SR-BI, apoM and apoC for the diagnosis of G-septic shock were 32.43%, 72.97%, 65.75%, and 43.24%, and specificity of 94.34%, 81.13%, 83.07%, and 86.79%, respectively. The AUC, sensitivity and specificity of apoM combined with SR-BI were improved.ConclusionHDL-associated lipoproteins were correlated with bacterial-infected types, and serum levels of HDL-associated lipoproteins can be used as potential biomarkers for early diagnosis and progress of G-sepsis. ApoM combined with SR-BI could improve the sensitivity and specificity of prognosis assessment.

Daeshiho-tang Attenuates Atherosclerosis by Regulating Cholesterol Metabolism and Inducing M2 Macrophage Polarization.

Dyslipidemia, the commonest cause of cardiovascular disease, leads to lipid deposits on the arterial wall, thereby aggravating atherosclerosis. DSHT (Daeshiho-tang) has long been used as an anti-dyslipidemia agent in oriental medicine. However, the anti-atherosclerotic effects of DSHT have not been fully investigated. Therefore, this study was designed to evaluate whether DSHT could exert beneficial anti-atherosclerotic effects. We fed apolipoprotein E-deficient (ApoE-/-) mice on a high-fat diet and treated them with atorvastatin (AT) or DSHT, or the combination of DSHT and AT for 12 weeks. To determine the role of DSHT, atherosclerotic lesions in the aorta, aortic root, and aortic arch; lipids and apolipoprotein levels in serum; and macrophage polarization markers in aorta tissues were examined. We show here that the DSHT decreased the atherosclerotic plaque ratio in the aortic arch, aorta, and aortic root. DSHT also regulated lipid levels by decreasing the ApoB level and increasing the ApoA1 level. Moreover, DSHT effectively regulated cholesterol metabolism by increasing the levels of PPARγ, ABCA1 and ABCG1, and the LDL receptor genes. We further found that DSHT promoted polarization to the M2 phenotype by increasing the levels of M2 macrophage (ARG1, CD163, and PPARγ) markers. Our data suggested that DSHT enhances the anti-atherosclerotic effect by regulating cholesterol metabolism through the activation of the PPARγ signaling pathway and by promoting anti-inflammatory M2 macrophage polarization.

Identification of serum proteins in dogs naturally infected with Anaplasma phagocytophilum and Borrelia burgdorferi: a pilot study

Serum proteomic analysis would aid in better understanding the pathophysiology of several diseases. The aim of this study was to identify the serum proteomes of dogs with anaplasmosis and Lyme disease using a proteomic approach. Diseases were diagnosed by a commercial rapid in-clinic ELISA. Borrelia antibodies were evaluated by IFAT. Four groups were designated: symptomatic dogs with anaplasmosis (n=5), dogs with Lyme disease (n=5), dual-positive dogs (n=5), and healthy control dogs (n=5). Serum samples were collected before treatment. Two-dimensional electrophoresis of pooled samples in each group were run in triplicate. Ten out of 57 differentially expressed spots between groups were evaluated for identification by mass spectrometry. Compared to those of controls, levels of vitamin D-binding protein (VDBP), glycoprotein-9 (GP9) and kininogen-1 (KGN-1) decreased, while haptoglobin (Hp) and immunoglobulin (Ig) heavy chain levels increased in dual infection group. Serum apolipoprotein-A1 (Apo-A1) levels decreased in dogs with anaplasmosis, Lyme disease and dual infections compared to those in control dogs. Serum clusterin levels decreased in dogs with anaplasmosis but were not differentially expressed in dogs with Lyme disease or dogs with dual infections compared to those in control dogs. Calpain-3 decreased in dogs with anaplasmosis and Lyme disease. This study showed that many protein levels might be changed in dogs with naturally acquired anaplasmosis and Lyme disease. Understanding the role of these proteins in different biological processes can provide information of interest for diagnostic and therapeutic approaches for these clinical conditions.

Serum Metabolomics in Patients with Coexisting NAFLD and T2DM Using Liquid Chromatography-Mass Spectrometry.

Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) frequently coexist and can act synergistically to drive adverse outcomes of one another. This study aimed to unravel the metabolomic changes in patients with NAFLD and T2DM, to identify potential noninvasive biomarkers, and to provide insights for understanding the link between NAFLD and T2DM. Three hundred participants aged 35 to 70 years who were diagnosed with NAFLD (n = 100), T2DM (n = 100), or a comorbidity of NAFLD and T2DM (n = 100) were included in this study. Anthropometrics and routine blood chemistry were assessed after overnight fast. The global serum metabolomic analysis was performed by ultra-performance liquid chromatography-Orbitrap mass spectrometry. Multivariate data analysis methods were utilized to identify the potential biomarkers. A set of serum biomarkers that could effectively separate NAFLD from NAFLD + T2DM and T2DM from NAFLD + T2DM were identified. We found that patients with coexisting NAFLD and T2DM had significantly higher levels of total protein (TP), triglycerides (TG), glucose in urine, and gamma-hydroxybutyric acid than those with NAFLD and had significant increased levels of TP, albumin, alanine aminotransferase, aspartate aminotransferase, total cholesterol, cholinesterase, TG, low-density lipoprotein, and apolipoprotein A when compared to patients with T2DM. The metabolomics results provide evidence that the comorbidity of NAFLD and T2DM considerably altered patients' metabolomics patterns compared to those of patients with only NAFLD or T2DM.

Lipid profile, lipid ratios, apolipoproteins, and risk of cardiometabolic multimorbidity in men: The Kuopio Ischaemic Heart Disease Risk Factor Study.

The blood level of lipids, apolipoproteins, and lipid ratios are important predictors of some chronic diseases. However, their association with cardiometabolic multimorbidity (CMM) is less known. We evaluated a wide range of lipid profiles and lipid ratios, including low‐density lipoprotein‐cholesterol (LDL‐C), very‐low‐density lipoprotein‐cholesterol (VLDL‐C), high‐density lipoprotein‐cholesterol (HDL‐C), and apoA1 and B, as well triglyceride and total cholesterol with risk of incident CMM. In 1728 men aged 52.5 ± 5.2 years from the Kuopio Ischaemic Heart Disease were included in this study. We defined CMM as coexisting of two or more of stroke, type 2 diabetes mellitus (T2D), coronary heart disease (CHD). A Cox proportional hazard regression method was applied to evaluate the risk of CMM against the exposures. During the mean follow‐up of 22.4 years, 335 men suffered from CMM conditions. Higher serum triglyceride and VLDL concentrations were associated with a higher risk of coexisting T2D‐CHD (HRs 1.99 (95% CI, 1.12–3.53) and HRs 1.79 (95% CI, 1.04–3.11), respectively. Whereas higher HDL was associated with lower incident [HRs 0.49 (95% CI, 0.40–1.00)]. The HRs for coexisting T2D‐CHD was 2.02 (95% CI, 1.01–3.07) for total cholesterol/HDL‐C, 1.85 (95% CI, 1.04–3.29) for triglyceride/HDL‐C, 1.69 (95% CI, 1.01–2.31) for Non‐HDL‐C/HDL‐C, and 1.89 (95% CI, 1.03–2.46) for apoB/apoA1. In contrast, serum LDL‐C/apoB ratios were inversely associated with the risk of coexisting T2D‐CHD [HRs 0.50 (95% CI, 0.28–0.90)]. No associations were observed between our exposures and other CMM conditions. In conclusion, elevated triglyceride, VLDL‐C, total cholesterol/HDL‐C, TG/HDL‐C, apoB/apoA1 as well as lower LDL‐C/apoB were independently associated with the higher risk of T2D‐CHD coexistence.

Pathogenesis and Biomarkers of Metabolic Syndrome

Metabolic syndrome (MetS) is a pathologic multifaceted condition characterized by elevated triacylglycerides, decreased high density lipoproteins, insulin resistance, increased blood pressure and fasting glucose. Together these abnormalities increase a risk of cardiovascular diseases and type 2 diabetes mellitus. Overnutrition and sedentary lifestyle followed by overweight and obesity are the main contributing factors to MetS development. The pathogenesis of MetS is very complex and not fully elucidated. The studies support the concept of oxidant/antioxidant imbalance and low-grade inflammation playing main roles in its manifestations. Diagnosis with MetS and the development of MetS complications can be detected and monitored via specific serum biomarkers. In this paper, we describe classical metabolic, hormonal and pro-/anti-inflammatory markers which are the most frequently used for MetS diagnostic and research. They include serum lipid profile (triacylglycerides, total cholesterol, low and high density lipoproteins), blood pressure, fasting glucose and HOMA-IR index, levels of anti-inflammatory adiponectin, pro-inflammatory C-reactive protein and cytokines (TNF-α, IL-1β, IL-6, etc.). We also analyze advantages of additional criteria such as levels of oxidative damages, appetite hormones (leptin, ghrelin), apolipoproteins and oxylipins, the composition of gut microbiota and levels of microbiome-derived metabolites, the ratios between different parameters as helpful biomarkers of MetS and concomitant cardiovascular diseases.

Targeting hippocampal amyloidogenesis with SV2A protein modulator levetiracetam

Cerebral amyloid β (Aβ) proteostasis is compromised under neuronal overexcitation, long-term neuroinflammation and brain aging. Using the animal model of LPS-induced neuroinflammation we demonstrated that treatment with levetiracetam, a specific modulator of synaptic vesicle glycoprotein SV2A, rescues abnormal synaptic vesicle (SV) fusion and neurotransmitter release, decreasing elevated hippocampal APP levels in vivo. Therapy with levetiracetam upregulates the SV2A in hippocampus and restores the level of apolipoprotein E, involved in brain Aβ aggregation/clearance and resolution of inflammation.We demonstrated that oligomers of Aβ1-42 and Aβ1-40 peptides promote SV clustering, which reduces the rate and plateau level of subsequent homo- and heterotypic SNARE-mediated SV fusion. Oligomeric Aβ1-42 lowered ΔpH gradient across the vesicular membrane, thus affecting their neurotransmitter storage capacity. In contrast, monomers of Aβ1-42 and Aβ1-40 had negligible impact on studied processes.Our data suggests that in the course of progression of neuroinflammation oligomeric forms of Aβ1-42 and Aβ1-40 can compromise the SV fusion machinery and that antiepileptic agent levetiracetam, acting on SV recycling and restricting overexcitation, is able to affect APP processing and Aβ generation within the hippocampus in vivo.