Prevalence of Metabolic Syndrome and Its Risk Factors Influence on Microvascular Complications in Patients With Type 1 and Type 2 Diabetes Mellitus.

BACKGROUND: Diabetes mellitus (DM) long-term macrovascular and microvascular complications pose significant health risks and increase mortality. In DM patients, metabolic syndrome (MetSy) either precedes or coexists with the condition. Central obesity, poor glycemic control, hypertension, elevated triglycerides (TG), and low high-density lipoproteins (HDL-C) are the components of MetSy. The purpose of this study is to investigate related diabetic microvascular complications in type 1 DM (T1DM) by comparing them with type 2 DM (T2DM), determine potential risk factors, and estimate prevalence based on the diagnosis of MetSy. METHODOLOGY: This study included 160 T1DM and 160 T2DM patients, totaling 320 DM patients. It was carried out from April 20, 2022, to September 31, 2023, at the Sheikh Zayed Hospital, Rahim Yar Khan, in the Outdoor Diabetic Clinic and Medicine Department. A unique questionnaire was utilized to gather socio-demographic, general, clinical, and laboratory data for the MetSy criteria set forth by the International Diabetes Federation (IDF). The blood pressure, BMI, and waist circumference (WC) were measured, while venous fasting blood was used to assess biochemical markers such as HDL-C, TG, and fasting blood sugar. The microvascular diabetes complications were identified using abdominal ultrasound, fundus ophthalmoscopy, and routine laboratory tests. We quantified and analyzed these variables individually for T1DM and T2DM patients with or without MetSy and compared them in the presence or absence of diabetes microvascular complications. RESULTS: MetSy prevalence was 25.62% (41, n=160) for T1DM and 60.62% (97, n=160) for T2DM, totaling 43.12%. Among T1DM patients with MetSy, the majority were married males, aged 36-49 years, with a BMI of 26.69±2.20 kg/m2 and a WC of 85.12±4.23, and 67.5% (108) patients had diabetes microvascular complications. Comparatively, in T2DM with MetSy, the majority were married females aged 50-59 years with a BMI of 29.79 ± 4.65 kg/m² and a large WC of 93.43±4.49, and 75% (123) patients had diabetes microvascular complications. Overall, this study noted significant p-values for hypertension, elevated TG, low HDL-c, high WC, obesity, female gender in T2DM, and above 36 years of age in both groups with MetSy. Diabetic retinopathy (DR) at 32.4% (p<0.001) was the most prevalent T1DM microvascular complication, followed by nephropathy (30.6%), neuropathy (DN) at 28.1%, and gastroparesis (DG) at 22.3%. Whereas in T2DM, the prevalence of DN was 36.3% (p<0.001), followed by DKD (29.3%), DG (28.9%), and DR (24.9%). CONCLUSION: Nearly a quarter of T1DM patients had MetSy, with increasing percentages of overweight and obese patients who are more likely to have DR, DKD, or DN. MetSy affects two-thirds of T2DM patients, with married obese females aged 50-59 being more susceptible than males, who are more likely to suffer DN, DKD, or DG. Risk factors that contribute to the MetSy burden in T1DM and T2DM include hypertension, poor glycemic management, low HDL-C, high TG, and a higher BMI or WC. Increasing age, female gender in T2DM, longer diabetes duration, and co-morbid hypertension were independent predictors of microvascular complications. DR, DN, DKD, and gastroparesis are the most prevalent diabetic microvascular sequelae. The clinical management of diabetic patients with healthy lifestyle adaptations, good glycemic control, antihypertensives, and statins will contribute greatly to MetSy prevention.

Antihyperlipidemic effect and GC-MS analysis of phytoconstituents from Laurus nobilis essential oil in rat.

This study aimed to evaluate the effect of Laurus nobilis (L. nobilis) essential oil (EOs) (80 mg/kg) on Triton WR-1339-induced dyslipidemia in Wistar rats. The effect of L. nobilis essential oil (80 mg/kg) on lipid and lipoprotein profile was examined on Triton WR-1339-induced dyslipidemia in rats. Furthermore, the phytochemical evaluation was performed by GC-MS. In Addition, the acute toxicity of this EO was evaluated at a dose of 2 g/kg. The results revealed that the main constituents of L. nobilis EO were 1,8-cineole (39.5%), linalool (13.09%), and a-terpineol (11.55%). Furthermore, the EO did not cause any signs of toxicity or mortality, and the acute lethal dose 50 (LD50) was estimated to be higher than 2 g/kg. L. nobilis EO ameliorated lipid parameters and atherogenic indices. In conclusion, the study demonstrates that L. nobilis essential oils possess antidyslipidemic activity in acute model of hyperlipidaemia.

Bacterial surface lipoproteins mediate epithelial microinvasion by Streptococcus pneumoniae.

Streptococcus pneumoniae, a common colonizer of the upper respiratory tract, invades nasopharyngeal epithelial cells without causing disease in healthy participants of controlled human infection studies. We hypothesized that surface expression of pneumococcal lipoproteins, recognized by the innate immune receptor TLR2, mediates epithelial microinvasion. Mutation of lgt in serotype 4 (TIGR4) and serotype 6B (BHN418) pneumococcal strains abolishes the ability of the mutants to activate TLR2 signaling. Loss of lgt also led to the concomitant decrease in interferon signaling triggered by the bacterium. However, only BHN418 lgt::cm but not TIGR4 lgt::cm was significantly attenuated in epithelial adherence and microinvasion compared to their respective wild-type strains. To test the hypothesis that differential lipoprotein repertoires in TIGR4 and BHN418 lead to the intraspecies variation in epithelial microinvasion, we employed a motif-based genome analysis and identified an additional 525 a.a. lipoprotein (pneumococcal accessory lipoprotein A; palA) encoded by BHN418 that is absent in TIGR4. The gene encoding palA sits within a putative genetic island present in ~10% of global pneumococcal isolates. While palA was enriched in the carriage and otitis media pneumococcal strains, neither mutation nor overexpression of the gene encoding this lipoprotein significantly changed microinvasion patterns. In conclusion, mutation of lgt attenuates epithelial inflammatory responses during pneumococcal-epithelial interactions, with intraspecies variation in the effect on microinvasion. Differential lipoprotein repertoires encoded by the different strains do not explain these differences in microinvasion. Rather, we postulate that post-translational modifications of lipoproteins may account for the differences in microinvasion.IMPORTANCEStreptococcus pneumoniae (pneumococcus) is an important mucosal pathogen, estimated to cause over 500,000 deaths annually. Nasopharyngeal colonization is considered a necessary prerequisite for disease, yet many people are transiently and asymptomatically colonized by pneumococci without becoming unwell. It is therefore important to better understand how the colonization process is controlled at the epithelial surface. Controlled human infection studies revealed the presence of pneumococci within the epithelium of healthy volunteers (microinvasion). In this study, we focused on the regulation of epithelial microinvasion by pneumococcal lipoproteins. We found that pneumococcal lipoproteins induce epithelial inflammation but that differing lipoprotein repertoires do not significantly impact the magnitude of microinvasion. Targeting mucosal innate immunity and epithelial microinvasion alongside the induction of an adaptive immune response may be effective in preventing pneumococcal colonization and disease.

Effects of portable pedal machines at work on lipoprotein subfraction profile in sedentary workers - the REMOVE study.

BACKGROUND: Sedentary behaviour at work is a major cause of atherosclerosis, particularly in tertiary workers. However, no studies have ever assessed the effect of active workstation on lipoprotein subfraction profile. This study aimed to evaluate the effect of 12-week portable pedal machines (PPMs) on lipoprotein subfraction profile among healthy sedentary workers. METHODS: Healthy administrative workers were randomized into an intervention group using PPMs for 12 weeks or a control group using normal-desk. Lipoprotein subfractions were assessed using Lipoprint® electrophoresis. Main outcomes were explored using mixed models with sensitivity analyses (four models). RESULTS: We included 40 participants (43.7 ± 8.6 years old, 100% women, BMI 23.8 ± 3.4 kg/m2; sedentary time at work 7.7 ± 1.8 h/day). Groups did not differ at baseline in any outcomes. 32 participants finished the trial. Changes in lipoprotein subfractions were especially marked for LDL profile. There was an interaction time x group for all parameters related to LDL and their subfractions: total LDL-cholesterol (p = 0.012), LDL particle size (p = 0.027), large LDL subfractions 1 and 2 (p = 0.001), and small dense LDL subfractions 3 to 7 (p = 0.046), using the crude model. The interaction reflects difference in the direction of changes between groups. The LDL particle size significantly increased in the intervention group (from 271.9 ± 2.5 at t0 to 272.8 ± 1.9 Ångström at t1, p = 0.037) while it did not change in the control group (272.5 ± 1.7 at t0 to 271.8 ± 1.5Å at t1, p = 0.52). All interactions were constantly significant whatever the models. Influencing variables were mainly stress at work that was associated with an increase in total LDL-cholesterol (coefficient 3.15, 95CI 0.20 to 6.11 mg/dl, p = 0.038), and BMI that was associated with Large-LDL, Large-HDL, IDL-C and triglycerides. CONCLUSIONS: Lipoprotein profile was improved after a 12-week PPMs intervention at work in healthy administrative workers. Changes were mainly showed for LDL and LDL subfractions. Lipoprotein profile was worsened by stress at work, BMI and age. TRIAL REGISTRATION: NCT04153214.

Circulating Lipoproteins Mediate the Association Between Cardiovascular Risk Factors and Cognitive Decline: A Community-Based Cohort Study.

Cardiovascular health metrics are now widely recognized as modifiable risk factors for cognitive decline and dementia. Metabolic perturbations might play roles in the linkage of cardiovascular diseases and dementia. Circulating metabolites profiling by metabolomics may improve understanding of the potential mechanism by which cardiovascular risk factors contribute to cognitive decline. In a prospective community-based cohort in China (n = 725), 312 serum metabolic phenotypes were quantified, and cardiovascular health score was calculated including smoking, exercise, sleep, diet, body mass index, blood pressure, and blood glucose. Cognitive function assessments were conducted in baseline and follow-up visits to identify longitudinal cognitive decline. A better cardiovascular health was significantly associated with lower risk of concentration decline and orientation decline (hazard ratio (HR): 0.84-0.90; p < 0.05). Apolipoprotein-A1, high-density lipoprotein (HDL) cholesterol, cholesterol ester, and phospholipid concentrations were significantly associated with a lower risk of longitudinal memory and orientation decline (p < 0.05 and adjusted-p < 0.20). Mediation analysis suggested that the negative association between health status and the risk of orientation decline was partly mediated by cholesterol ester and total lipids in HDL-2 and -3 (proportion of mediation: 7.68-8.21%, both p < 0.05). Cardiovascular risk factors were associated with greater risks of cognitive decline, which were found to be mediated by circulating lipoproteins, particularly the medium-size HDL components. These findings underscore the potential of utilizing lipoproteins as targets for early stage dementia screening and intervention. Supplementary Information: The online version contains supplementary material available at 10.1007/s43657-023-00120-2.

Lipoprotein alterations in endocrine disorders - a review of the recent developments in the field.

Dyslipidemia is one of the most common disorders worldwide, which, if left untreated, results in a multitude of complications. Thus proper diagnostics, which includes identifying of secondary causes of dyslipidemia is crucial. Endocrine disorders are an important cause of secondary dyslipidemia. This paper aims to review the publications on lipoprotein alterations in endocrine disorders from the past two years and provide an overview of the recent discoveries in this dynamically developing and large field. Significant changes in lipoprotein serum concentrations are present in most endocrinological diseases and can be modified with proper treatment. Some lipoproteins have also been proposed as markers in some endocrine diseases, e.g., thyroid carcinoma. From the scope of endocrine disorders, the largest number of studies explored the lipoprotein changes in polycystic ovary syndrome and in women during the menopausal and peri-menopausal period. Even though the association of thyroid disorders with dyslipidemia is already well studied, new research has delivered some exciting findings about lipoprotein alterations in euthyroid patients with either positive antithyroid peroxidase antibodies or reduced sensitivity to thyroid hormones. The problem of the adverse metabolic profile, including dyslipidemia in hypoprolactinemia has been recognized. Moreover, this review describes other significant discoveries encompassing lipoprotein alterations in disorders of the adrenals, thyroid, parathyroid glands, pituitary, and gonads. The up-to-date knowledge of the influence of endocrine disorders and hormonal changes on serum lipoproteins is prudent as it can significantly impact therapeutic decisions.

Value of the monocyte-to-high-density lipoprotein cholesterol ratio in refining the detection of prevalent heart failure: Insights from the NHANES 1999-2018.

The monocyte-to-high-density lipoprotein cholesterol ratio (MHR) is a novel marker that can help estimate the degree of atherosclerosis by considering inflammation and lipid abnormalities. This study aimed to assess the association between the MHR and prevalent heart failure (HF) and to explore the value of the MHR in detecting prevalent HF in the general US population. Our study included 25,374 participants from the National Health and Nutrition Examination Survey (1999-2018). Among the participants, 749 (2.95%) reported a history of HF, and the HF group had a significantly higher MHR than the non-HF group. Adjusted analyses revealed that each standard deviation increase in the MHR was associated with a 27.8% increase in the risk of HF. The association between the MHR and prevalent HF was linear across the entire MHR range. Adding the MHR to conventional cardiovascular risk factors significantly improved the area under the curve (0.875; p < 0.001), continuous net reclassification index (0.187; p < 0.001), and integrated discrimination index (0.004; p < 0.001). Our study suggests a potential association between the MHR and HF risk, and the findings enhance HF risk stratification and provide novel insights into the interplay between the coronary atherosclerotic burden and HF in clinical settings.

Medical Nutrition Therapy Provided by a Dietitian Improves Outcomes in Adults with Pre-Hypertension or Hypertension: A Systematic Review and Meta-Analysis.

BACKGROUND: Hypertension is an important risk factor for cardiovascular disease. Interventions with dietitians can help modify dietary intake and reduce hypertension risk. OBJECTIVE: To examine the research question: In adults with pre-hypertension or hypertension, what is the effect of medical nutrition therapy (MNT) provided by a dietitian on blood pressure (BP), cardiovascular risk and events and anthropometrics compared to standard care or no intervention? METHODS: MEDLINE, CINAHL and Cochrane Central databases were searched for randomized controlled trials (RCTs) published in peer-reviewed journals from 1985-2022. Risk of bias (RoB) was assessed using the version 2 of the Cochrane tool for RCTs. Meta-analyses were conducted using the DerSimonian-Laird random-effects model. Certainty of evidence (COE) was assessed for each outcome using the Grading of Recommendations, Assessment, and Evaluation (GRADE) method. RESULTS: Forty articles representing 31 RCTs were included and analyzed. MNT provided by a dietitian likely reduces systolic [Mean Difference (MD): -3.63 mmHg (95% confidence interval (CI): -4.35, -2.91)] and diastolic [-2.02 mmHg (-2.56, -1.49)] BP (p<0.001) and body weight [-1.84 kg (-2.72, -0.96), p<0.001], and improves anti-hypertensive medication usage, relative risk of stroke [0.34 (0.14, 0.81), p=0.02] and CVD risk score [standardized mean difference (SMD): -0.20 (-0.30, -0.09), p<0.001] compared to control participants, and COE was moderate. Additionally, MNT may reduce arterial stiffness [SMD: -0.45 (-0.71, -0.19), p=0.008] and waist circumference [-1.18 cm (-2.00, -0.36), p=0.04], and COE was low. There was no significant difference in risk for myocardial infarction between groups. Dietitian interventions reduced BP and related cardiovascular outcomes for adults with pre-hypertension or hypertension. CONCLUSION: Dietitians play a critical role in improving cardiometabolic risk factors for adults with elevated BP; thus, improved payment for and access to MNT services has the potential to significantly impact public health. REGISTRATION ID AND URL: This systematic review was registered in the International Prospective Register of Systematic Reviews: PROSPERO# CRD42022351693 (https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351693).

Interactions Between HDL and CD4+ T Cells: A Novel Understanding of HDL Anti-Inflammatory Properties.

Several studies in animal models and human cohorts have recently suggested that HDLs (high-density lipoproteins) not only modulate innate immune responses but also adaptative immune responses, particularly CD4+ T cells. CD4+ T cells are central effectors and regulators of the adaptive immune system, and any alterations in their homeostasis contribute to the pathogenesis of cardiovascular diseases, autoimmunity, and inflammatory diseases. In this review, we focus on how HDLs and their components affect CD4+ T-cell homeostasis by modulating cholesterol efflux, immune synapsis, proliferation, differentiation, oxidative stress, and apoptosis. While the effects of apoB-containing lipoproteins on T cells have been relatively well established, this review focuses specifically on new connections between HDL and CD4+ T cells. We present a model where HDL may modulate T cells through both direct and indirect mechanisms.

CETP inhibition enhances monocyte activation and bacterial clearance and reduces streptococcus pneumonia-associated mortality in mice.

Sepsis is a leading cause of mortality worldwide, and pneumonia is the most common cause of sepsis in humans. Low levels of high-density lipoprotein cholesterol (HDL-C) levels are associated with an increased risk of death from sepsis, and increasing levels of HDL-C by inhibition of cholesteryl ester transfer protein (CETP) decreases mortality from intraabdominal polymicrobial sepsis in APOE*3-Leiden.CETP mice. Here, we show that treatment with the CETP inhibitor (CETPi) anacetrapib reduced mortality from Streptococcus pneumoniae-induced sepsis in APOE*3-Leiden.CETP and APOA1.CETP mice. Mechanistically, CETP inhibition reduced the host proinflammatory response via attenuation of proinflammatory cytokine transcription and release. This effect was dependent on the presence of HDL, leading to attenuation of immune-mediated organ damage. In addition, CETP inhibition promoted monocyte activation in the blood prior to the onset of sepsis, resulting in accelerated macrophage recruitment to the lung and liver. In vitro experiments demonstrated that CETP inhibition significantly promoted the activation of proinflammatory signaling in peripheral blood mononuclear cells and THP1 cells in the absence of HDL; this may represent a mechanism responsible for improved bacterial clearance during sepsis. These findings provide evidence that CETP inhibition represents a potential approach to reduce mortality from pneumosepsis.

Evaluation of lipoproteins and high sensitivity crp in consumers of bakery products.

Background: In recent years, a wider range of bakery products with a lower glycaemic response can be observed in the food industry. This contributes to the provision of a wider range of cereal bakery products. The gradual increase in the consumption of brown bread is significant, but despite this, white bread remains a part of the typical Western diet. Studies showed high intake of carbohydrates increase TG levels by enhancing hepatic synthesis of very low-density lipoprotein (VLDL) and decrease activity of lipoprotein lipase. White bread consumption has been therefore associated with an unhealthy lifestyle. Objective: The aim of this study was to assess the influence of the consumption of gluten bakery products on lipids and inflammatory parameters of the probands. Material and Methods: The monitored group consisted of 30 probands from the general population. The average age of the monitored group was 29.7 years. The intervention dose consisted of a different combination of several types of bakery products containing gluten (bread, pastries, soft pastries) within the individual weeks of consumption, while the intervention lasted 6 weeks. An intervention dose of 150 to 200 g per day was set for women and 200 to 250 g per day for men. Biochemical blood parameters were determined using a fully automatic Biolis 24i Premium blood serum biochemical analyzer, by end-point photometry method. We tested the differences between the biochemic parameters by one-factor analysis of variance (ANOVA) and compared them by Tuckey's Post Hoc Test. Results: The measurement of the lipid profile showed that the average levels of total cholesterol (TC) were above the reference value (<5.00 mmol. l-1) in each of the three performed measurements (P˂0.01). In the case of LDL, we found a similar trend in the development of lipoprotein values, while we positively evaluate a slight reduction of LDL in the measurement immediately after the intervention (P˂0.001). Certain changes during the study were also noted in HDL parameters with high statistical significance (P˂0.001). During the TG analysis, we found that probands have normal values(0.45-2.70 mmol. l-1). A reduction in average TG values was achieved in individual measurements, but without statistical significance (P˃0.05). In high sensitivity CRP (hs-CRP) parameters was achieved a bell curve of the development of average values, with a maximum measured immediately after the intervention. Changes in hs-CRP during the study were without statistical significance (P˃0.05). Conclusions: The measurement of the lipid profile showed that the average levels of TC, LDL and HDL, there were above the reference value in each of the three measurements performed. Through the analysis of TG, we found normal values and during the study there was a slight decrease. Furthermore, we found that intervention with bakery products containing gluten was associated with an increase in hs-CRP levels in our probands.

Hepatic insulin resistance and muscle insulin resistance are characterized by distinct postprandial plasma metabolite profiles: a cross-sectional study.

BACKGROUND: Tissue-specific insulin resistance (IR) predominantly in muscle (muscle IR) or liver (liver IR) has previously been linked to distinct fasting metabolite profiles, but postprandial metabolite profiles have not been investigated in tissue-specific IR yet. Given the importance of postprandial metabolic impairments in the pathophysiology of cardiometabolic diseases, we compared postprandial plasma metabolite profiles in response to a high-fat mixed meal between individuals with predominant muscle IR or liver IR. METHODS: This cross-sectional study included data from 214 women and men with BMI 25-40 kg/m2, aged 40-75 years, and with predominant muscle IR or liver IR. Tissue-specific IR was assessed using the muscle insulin sensitivity index (MISI) and hepatic insulin resistance index (HIRI), which were calculated from the glucose and insulin responses during a 7-point oral glucose tolerance test. Plasma samples were collected before (T = 0) and after (T = 30, 60, 120, 240 min) consumption of a high-fat mixed meal and 247 metabolite measures, including lipoproteins, cholesterol, triacylglycerol (TAG), ketone bodies, and amino acids, were quantified using nuclear magnetic resonance spectroscopy. Differences in postprandial plasma metabolite iAUCs between muscle and liver IR were tested using ANCOVA with adjustment for age, sex, center, BMI, and waist-to-hip ratio. P-values were adjusted for a false discovery rate (FDR) of 0.05 using the Benjamini-Hochberg method. RESULTS: Sixty-eight postprandial metabolite iAUCs were significantly different between liver and muscle IR. Liver IR was characterized by greater plasma iAUCs of large VLDL (p = 0.004), very large VLDL (p = 0.002), and medium-sized LDL particles (p = 0.026), and by greater iAUCs of TAG in small VLDL (p = 0.025), large VLDL (p = 0.003), very large VLDL (p = 0.002), all LDL subclasses (all p < 0.05), and small HDL particles (p = 0.011), compared to muscle IR. In liver IR, the postprandial plasma fatty acid (FA) profile consisted of a higher percentage of saturated FA (p = 0.013), and a lower percentage of polyunsaturated FA (p = 0.008), compared to muscle IR. CONCLUSION: People with muscle IR or liver IR have distinct postprandial plasma metabolite profiles, with more unfavorable postprandial metabolite responses in those with liver IR compared to muscle IR.

Impact of conjugation to different lipids on the lymphatic uptake and biodistribution of brush PEG polymers.

Delivery to peripheral lymphatics can be achieved following interstitial administration of nano-sized delivery systems (nanoparticles, liposomes, dendrimers etc) or molecules that hitchhike on endogenous nano-sized carriers (such as albumin). The published work concerning the hitchhiking approach has mostly focussed on the lymphatic uptake of vaccines conjugated directly to albumin binding moieties (ABMs such as lipids, Evans blue dye derivatives or peptides) and their subsequent trafficking into draining lymph nodes. The mechanisms underpinning access and transport of these constructs into lymph fluid, including potential interaction with other endogenous nanocarriers such as lipoproteins, have largely been ignored. Recently, we described a series of brush polyethylene glycol (PEG) polymers containing end terminal short-chain or medium-chain hydrocarbon tails (1C2 or 1C12, respectively), cholesterol moiety (Cho), or medium-chain or long-chain diacylglycerols (2C12 or 2C18, respectively). We evaluated the association of these materials with albumin and lipoprotein in rat plasma, and their intravenous (IV) and subcutaneous (SC) pharmacokinetic profiles. Here we fully detail the association of this suite of polymers with albumin and lipoproteins in rat lymph, which is expected to facilitate lymph transport of the materials from the SC injection site. Additionally, we characterise the thoracic lymph uptake, tissue and lymph node biodistribution of the lipidated brush PEG polymers following SC administration to thoracic lymph cannulated rats. All polymers had moderate lymphatic uptake in rats following SC dosing with the lymph uptake higher for 1C2-PEG, 2C12-PEG and 2C18-PEG (5.8%, 5.9% and 6.7% dose in lymph, respectively) compared with 1C12-PEG and Cho-PEG (both 1.5% dose in lymph). The enhanced lymph uptake of 1C2-PEG, 2C12-PEG and 2C18-PEG appeared related to their association profile with different lipoproteins. The five polymers displayed different biodistribution patterns in major organs and tissues in mice. All polymers reached immune cells deep within the inguinal lymph nodes of mice following SC dosing. The ability to access these immune cells suggests the potential of the polymers as platforms for the delivery of vaccines and immunotherapies. Future studies will focus on evaluating the lymphatic targeting and therapeutic potential of drug or vaccine-loaded polymers in pre-clinical disease models.

Fatty acids of Helicobacter pylori lipoproteins CagT and Lpp20.

Bacterial lipoproteins are post-translationally modified by the addition of acyl chains that anchor the protein to bacterial membranes. This modification includes two ester-linked and one amide-linked acyl chain on lipoproteins from Gram-negative bacteria. Helicobacter pylori lipoproteins have important functions in pathogenesis (including delivering the CagA oncoprotein to mammalian cells) and are recognized by host innate and adaptive immune systems. The number and variety of acyl chains on lipoproteins impact the innate immune response through Toll-like receptor 2. The acyl chains added to lipoproteins are derived from membrane phospholipids. H. pylori membrane phospholipids have previously been shown to consist primarily of C14:0 and C19:0 cyclopropane-containing acyl chains. However, the acyl composition of H. pylori lipoproteins has not been determined. In this study, we characterized the acyl composition of two representative H. pylori lipoproteins, Lpp20 and CagT. Fatty acid methyl esters were prepared from both purified lipoproteins and analyzed by gas chromatography-mass spectrometry. For comparison, we also analyzed H. pylori phospholipids. Consistent with previous studies, we observed that the H. pylori phospholipids contain primarily C14:0 and C19:0 cyclopropane-containing fatty acids. In contrast, both the ester-linked and amide-linked fatty acids found in H. pylori lipoproteins were observed to be almost exclusively C16:0 and C18:0. A discrepancy between the acyl composition of membrane phospholipids and lipoproteins as reported here for H. pylori has been previously reported in other bacteria including Borrelia and Brucella. We discuss possible mechanisms.IMPORTANCEColonization of the stomach by Helicobacter pylori is an important risk factor in the development of gastric cancer, the third leading cause of cancer-related death worldwide. H. pylori persists in the stomach despite an immune response against the bacteria. Recognition of lipoproteins by TLR2 contributes to the innate immune response to H. pylori. However, the role of H. pylori lipoproteins in bacterial persistence is poorly understood. As the host response to lipoproteins depends on the acyl chain content, defining the acyl composition of H. pylori lipoproteins is an important step in characterizing how lipoproteins contribute to persistence.

Investigating the Incidence of Dyslipidemia among Brazilian Children and Adolescents Diagnosed with Type 1 Diabetes Mellitus: A Cross-Sectional Study.

The treatment of Type 1 Diabetes Mellitus (T1DM) has always been a challenge for health professionals in relation to glycemic control. Increased body fat has been related to a worsening of the lipid profile and increased prevalence of dyslipidemia in this population, leading to negative repercussions on the control of cardiovascular risk. We aimed to investigate the distribution of lipid levels and the presence of dyslipidemia in children and adolescents with T1DM. A cross-sectional observational study was conducted with 81 individuals of both sexes (4-19 years) diagnosed with T1DM. Anthropometric and biochemical data were collected, in addition to data on physical activity level, sexual maturation stage, and insulin administration regimen. Lipid levels were categorized as normal, borderline, and elevated, and the presence of dyslipidemia was diagnosed by the presence of one or more altered lipid parameter. We noted a prevalence of dyslipidemia in 65.4% of the participants when considering borderline lipid values. Of those, 23.5% had one altered lipid level, and 42.0% had two or more. The main altered lipid levels were total cholesterol and triglycerides, followed by non-HDL-c. The main factor associated with the worsening of lipid levels was the increase in HbA1c. Sex had a significant effect on the levels of TC, HDL-c, and ApoA-I. The results of this study reinforce the need to monitor lipid profile in children and adolescents with T1DM, as well as the importance of early intervention in treating dyslipidemia, especially in patients with poor glycemic control.

The Significance of Lipoproteins in the Development of Obesity.

Disruption of lipoprotein metabolism plays an important role in the development of several cardiovascular, inflammatory, and metabolic diseases. This review examines the importance of different types of lipoproteins and the role they play in the development of dyslipidemia in obesity. The causes and consequences associated with the disruption of lipid metabolism and its significance in the pathogenesis of obesity are considered. The relationship between such pathological processes, which occur alongside obesity as dyslipidemia and inflammation, is determined. In view of the current efficacy and toxicity limitations of currently approved drugs, natural compounds as potential therapeutic agents in the treatment of obesity are considered in the review. The complex mechanisms of lipid metabolism normalization in obesity found for these compounds can serve as one of the confirmations of their potential efficacy in treating obesity. Nanoparticles can serve as carriers for the considered drugs, which can improve their pharmacokinetic properties.

Body composition in second trimester is associated with dyslipidemia in third trimester.

OBJECTIVE: The aim of this study was to examine the correlation between maternal body composition during the second trimester and the occurrence of dyslipidemia in the third trimester. METHODS: A cohort of 1508 pregnant women who underwent antenatal testing at Shanghai Sixth People's Hospital, affiliated with Shanghai Jiao Tong University School of Medicine, were included in this study. Maternal body composition was assessed using bioimpedance analysis between 14 and 22 weeks of gestation. RESULTS: Among the 1508 participants, a total of 1420 individuals (94.2%) were diagnosed with dyslipidemia. Notably, there were significant differences in body composition between the normal lipid group and the dyslipidemia group. Logistic regression analysis revealed that various factors including BMI, total body water (TBW), intra-cellular water (ICW), extra-cellular water (ECW), percent body fat (PBF), visceral fat area (VFA), fat-free mass (FFM) and arm circumference (AC) during the second trimester were all found to be associated with dyslipidemia in the third trimester. CONCLUSION: The present study found that maternal body composition was associated with dyslipidemia. The BMI, TBW, ICW, ECW, PBF, VFA, FFM and AC in second trimester were associated with dyslipidemia in third trimester.

Effect of Hormone Therapy on Lipoprotein Subfractions in Early and Late Postmenopausal Women.

CONTEXT: The Early vs Late Intervention Trial with Estradiol (ELITE) showed that hormone therapy (HT) reduced atherosclerosis progression among early but not late postmenopausal women (PMW). OBJECTIVE: Determined by time-since-menopause (1) HT effects on lipids and lipoprotein particle subfractions (LPs), (2) associations of estradiol (E2) level with lipids and LPs, (3) associations of lipids and LPs with atherosclerosis progression. DESIGN: Randomized controlled trial stratified by time-since-menopause. SETTING: Academic institution. PARTICIPANTS: Healthy postmenopausal women. INTERVENTION: Oral E2 with/without sequential vaginal progesterone. MAIN OUTCOME MEASURES: Standard lipids and 21 LPs quantitated by ion mobility every 6 months. RESULTS: Among 562 PMW (240 early, 322 late), HT significantly increased total triglycerides (TG), high-density lipoprotein (HDL) cholesterol, small low-density lipoproteins (LDL), large HDL, and TG/C ratio in LDL and HDL and decreased LDL-cholesterol, total very low density lipoproteins (VLDL), small VLDL, intermediate-density lipoproteins, large LDL, and LDL peak diameter. HT showed no lipid or LP differences between time-since-menopause. Associations of E2 level with lipids and LPs explained the HT effects. Despite the nonsignificant P interaction by time-since-menopause, we observed that very small LDL and total HDL LPs were associated with atherosclerosis progression in late PMW. CONCLUSION: HT effects on standard lipids and LPs are consistent with the literature. HT has similar effect on lipids and LPs in early and late PMW. Novel findings include discordant effects of HT on TG and VLDL particles, which can be explained by increased catabolism of atherogenic remnants of TG-rich lipoproteins. Our findings extend the well-known HT effects on standard lipids and LPs that may contribute to the beneficial effects on atherosclerosis progression in PMW.

Macrophages play a nutritive role in post-metamorphic maturation in Drosophila.

In the body of multicellular organisms, macrophages play an indispensable role in maintaining tissue homeostasis by removing old, apoptotic and damaged cells. In addition, macrophages allow significant remodeling of body plans during embryonic morphogenesis, regeneration and metamorphosis. Although the huge amount of organic matter that must be removed during these processes represents a potential source of nutrients, their further use by the organism has not yet been addressed. Here, we document that, during metamorphosis, Drosophila larval adipose tissue is infiltrated by macrophages, which remove dying adipocytes by efferocytosis and engulf leaking RNA-protein granules and lipids. Consequently, the infiltrating macrophages transiently adopt the adipocyte-like metabolic profile to convert remnants of dying adipocytes to lipoproteins and storage peptides that nutritionally support post-metamorphic development. This process is fundamental for the full maturation of ovaries and the achievement of early fecundity of individuals. Whether macrophages play an analogous role in other situations of apoptotic cell removal remains to be elucidated.