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BACKGROUND: Specific components of lipid profile seem to differently impact on immune activity against cancer and unraveling their prognostic role in patients with solid cancer treated with immune checkpoint inhibitors (ICIs) is needed. MATERIALS AND METHODS: We retrospectively collected baseline clinicopathological characteristics including circulating lipid profile (total cholesterol [TC], triglycerides [TG], low-density lipoproteins [LDL], high-density lipoproteins [HDL]) of patients with consecutive solid cancer treated with ICIs, and we investigated their role in predicting clinical outcomes. RESULTS: At a median follow-up of 32.9 months, among 430 enrolled patients, those with TCâ ≥â 200 mg/dl showed longer median progression-free survival (mPFS; 6.6 vs. 4.7 months, Pâ =â .4), although not reaching statistical significance, and significantly longer median overall survival (mOS; 19.4 vs. 10.8 months, Pâ =â .02) compared to those with TCâ <â 200 mg/dl. Conversely, patients with TG ≥150 mg/dl displayed shorter PFS (3.4 vs. 5.1 months, Pâ =â .02) and OS (7.1 vs. 12.9 months, Pâ =â .009) compared to those with TG <150 mg/dl. TC and TG were then combined in a "LIPID score" identifying three subgroups: good-risk (GR) (TC ≥200 mg/dl and TG <150 mg/dl), intermediate-risk (IR) (TC <200 mg/dl and TG <150 mg/dl or TC ≥200 mg/dl and TG ≥150 mg/dl) and poor-risk (PR) (TC <200 mg/dl and TG ≥150 mg/dl). The mPFS of GR, IR, and PR groups was 7.8, 4.3, and 2.5 months, respectively (Pâ =â .005); mOS of GR, IR, and PR was 20.4, 12.4, and 5.3 months, respectively (Pâ <â .001). At multivariable analysis, the PR profile represented an independent poor prognostic factor for both PFS and OS. CONCLUSIONS: We developed a lipid score that defined subgroups of patients with cancer who differently benefit from ICIs. Further mechanistic insights are warranted to clarify the prognostic and predictive role of lipid profile components in patients treated with ICIs.
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Inibidores de Checkpoint Imunológico , Neoplasias , Humanos , Estudos Retrospectivos , Prognóstico , Lipídeos , Triglicerídeos , Neoplasias/tratamento farmacológicoRESUMO
BACKGROUND: The challenge of addressing obesity persists in healthcare, necessitating nuanced approaches and personalized strategies. This study aims to evaluate the effects of diverse therapeutic interventions on anthropometric and biochemical parameters in individuals with overweight and obesity within a real-world clinical context. METHODS: A retrospective analysis was conducted on 192 patients (141 females, 51 males) aged 18 to 75, with a BMI ranging from 25 to 30 (14.1%) and BMI ≥ 30 (85.9%), observed over a 12-month period at our Endocrinology Unit. Treatment cohorts comprised individuals following different regimens: Mediterranean Diet (MD), with an approximate daily intake of 1500 kcal for women and 1800 kcal for men (71% patients); Ketogenic Diet (KD), utilizing the VLCKD protocol characterized by a highly hypocaloric dietary regimen < 800 kcal/day (14% patients); metformin, administered using the oral formulation (5% patients); pharmacological intervention with GLP1-RA administered via subcutaneous injection with incremental dosage (10% patients). Supply constraints limited the efficacy of Liraglutide, whereas Semaglutide was excluded from comparisons due to its unavailability for obesity without diabetes. Blood tests were conducted to assess lipid profile, glycemic profile, and anthropometric parameters, including BMI, waist circumference, and waist-to-height ratio. RESULTS: Significant BMI changes were observed from baseline to 6 months across MD, KD, and Liraglutide groups (p < 0.05). KD exhibited notable reductions in waist circumference and waist-to-height ratio within the initial quarter (p < 0.05), with a significant triglyceride decrease after 6 months (p < 0.05), indicating its efficacy over MD. Liraglutide demonstrated a substantial reduction in HbA1c levels in the first quarter (p < 0.05). During the first three months, the ANOVA test on fasting blood glucose showed a statistically significant impact of the time variable (p < 0.05) rather than the specific treatments themselves (Liraglutide and KD), suggesting that adherence during the early stages of therapy may be more critical than treatment choice. CONCLUSIONS: Positive outcomes from targeted interventions, whether pharmacological or dietary should encourage the exploration of innovative, long-term strategies that include personalized treatment alternation. The absence of standardized protocols underscores the importance of careful and tailored planning in managing obesity as a chronic condition.
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Obesidade , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Adolescente , Adulto Jovem , Manejo da Obesidade/métodos , Dieta Mediterrânea , Índice de Massa Corporal , Estudos RetrospectivosRESUMO
Human herpesvirus 8 (HHV-8) infection shows obvious regional and ethnic differences. Although studies have shown that these differences may be associated with lipid metabolism, to date, no large-scale studies have explored this. This study explored the seropositivity rate of HHV-8 among 2516 residents from 10 regions of northwest China and then the correlates of HHV-8 infection with lipid profile. The HHV-8 serological positivity rate was 15.6% among all residents. The HHV-8 seroprevalence ranged 11.2-27.6% among different ethnicities. Across different BMI levels, the positive rates of HHV-8 were 27.6%, 16.9%, and 13.6% for a BMI < 18.5, 18.5-24.9, and ≥25, respectively. HHV-8 seropositivity rate was lower for hypertensive people (12.6%) than for non-hypertensive people (16.7%). Univariate logistic regression analyses revealed that age, hypertension, systolic blood pressure, BMI, total cholesterol, and high-density lipoprotein cholesterol (HDL-C) significantly correlated with HHV-8 seropositivity (p < 0.05). Multivariate logistic regression analysis after adjusting for confounding factors showed that HDL-C (odds ratio [OR]: 0.132, 95% confidence interval [CI], 0.082-0.212; p < 0.001) and BMI (OR: 0.959, 95% CI 0.933-0.986; p = 0.003) were associated with HHV-8 seropositivity. Subgroup analyses concerning ethnicity, sex, or age demonstrated a consistent relationship with HDL-C. The results of HHV-8 seropositivity and BMI were inconsistent in the subgroups. However, Spearman's correlation analysis between HHV-8 serum antibody titer and HDL-C levels showed no linear relationship among HHV-8 seropositive individuals (ρ = -0.080, p = 0.058). HHV-8 serum antibody titers were also not significantly correlated with BMI (ρ = -0.015, p = 0.381). Low HDL-C levels may be an independent risk factor for HHV-8 infection, but there is no significant correlation between HDL-C levels and HHV-8 antibody titers.
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Infecções por Herpesviridae , Herpesvirus Humano 8 , Lipídeos , Humanos , Herpesvirus Humano 8/imunologia , China/epidemiologia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Transversais , Infecções por Herpesviridae/epidemiologia , Infecções por Herpesviridae/sangue , Infecções por Herpesviridae/virologia , Adulto , Estudos Soroepidemiológicos , Idoso , Lipídeos/sangue , Adulto Jovem , Adolescente , Anticorpos Antivirais/sangue , Fatores de Risco , Idoso de 80 Anos ou mais , Índice de Massa CorporalRESUMO
STUDY QUESTION: Are impaired glucose tolerance (as measured by fasting glucose, glycated hemoglobin, and fasting insulin) and cardiovascular disease risk (as measured by low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, triglycerides, systolic blood pressure, and diastolic blood pressure) causally related to infertility? SUMMARY ANSWER: Genetic instruments suggest that higher fasting insulin may increase infertility in women. WHAT IS KNOWN ALREADY: Observational evidence suggests a shared etiology between impaired glucose tolerance, cardiovascular risk, and fertility problems. STUDY DESIGN, SIZE, DURATION: This study included two-sample Mendelian randomization (MR) analyses, in which we used genome-wide association summary data that were publicly available for the biomarkers of impaired glucose tolerance and cardiovascular disease, and sex-specific genome-wide association studies (GWASs) of infertility conducted in the Norwegian Mother, Father, and Child Cohort Study. PARTICIPANTS/MATERIALS, SETTING, METHODS: There were 68â882 women (average age 30, involved in 81â682 pregnancies) and 47â474 of their male partners (average age 33, 55â744 pregnancies) who had available genotype data and who provided self-reported information on time-to-pregnancy and use of ARTs. Of couples, 12% were infertile (having tried to conceive for ≥12 months or used ARTs to conceive). We applied the inverse variance weighted method with random effects to pool data across variants and a series of sensitivity analyses to explore genetic instrument validity. (We checked the robustness of genetic instruments and the lack of unbalanced horizontal pleiotropy, and we used methods that are robust to population stratification.) Findings were corrected for multiple comparisons by the Bonferroni method (eight exposures: P-value < 0.00625). MAIN RESULTS AND THE ROLE OF CHANCE: In women, increases in genetically determined fasting insulin levels were associated with greater odds of infertility (+1 log(pmol/l): odds ratio 1.60, 95% CI 1.17 to 2.18, P-value = 0.003). The results were robust in the sensitivity analyses exploring the validity of MR assumptions and the role of pleiotropy of other cardiometabolic risk factors. There was also evidence of higher glucose and glycated hemoglobin causing infertility in women, but the findings were imprecise and did not pass our P-value threshold for multiple testing. The results for lipids and blood pressure were close to the null, suggesting that these did not cause infertility. LIMITATIONS, REASONS FOR CAUTION: We did not know if underlying causes of infertility were in the woman, man, or both. Our analyses only involved couples who had conceived. We did not have data on circulating levels of cardiometabolic risk factors, and we opted to conduct an MR analysis using GWAS summary statistics. No sex-specific genetic instruments on cardiometabolic risk factors were available. Our results may be affected by selection and misclassification bias. Finally, the characteristics of our study sample limit the generalizability of our results to populations of non-European ancestry. WIDER IMPLICATIONS OF THE FINDINGS: Treatments for lower fasting insulin levels may reduce the risk of infertility in women. STUDY FUNDING/COMPETING INTEREST(S): The MoBa Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Norwegian Ministry of Education and Research. This work was supported by the European Research Council [grant numbers 947684, 101071773, 293574, 101021566], the Research Council of Norway [grant numbers 262700, 320656, 274611], the South-Eastern Norway Regional Health Authority [grant numbers 2020022, 2021045], and the British Heart Foundation [grant numbers CH/F/20/90003, AA/18/1/34219]. Open Access funding was provided by the Norwegian Institute of Public Health. The funders had no role in the study design; the collection, analysis, and interpretation of data; the writing of the report; or the decision to submit the article for publication. D.A.L. has received research support from National and International government and charitable bodies, Roche Diagnostics and Medtronic for research unrelated to the current work. O.A.A. has been a consultant to HealthLytix. The rest of the authors declare that no competing interests exist. TRIAL REGISTRATION NUMBER: N/A.
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Doenças Cardiovasculares , Intolerância à Glucose , Infertilidade Feminina , Gravidez , Criança , Feminino , Masculino , Humanos , Adulto , Intolerância à Glucose/complicações , Doenças Cardiovasculares/genética , Análise da Randomização Mendeliana , Mães , Estudos de Coortes , Estudo de Associação Genômica Ampla , Hemoglobinas Glicadas , Fatores de Risco , Infertilidade Feminina/genética , Infertilidade Feminina/complicações , Glucose , Fatores de Risco de Doenças Cardíacas , Insulina , Colesterol , PaiRESUMO
BACKGROUND: Considering the conflicting effects of bupropion on parameters related to metabolic syndrome including glucose metabolism and lipid profile, in this meta-analysis study, we investigated the effects of this drug alone or in combination with naltrexone on glucose metabolism and lipid profile. METHODS: Scopus, PubMed/Medline, Web of Science and Embase databases were searched using standard keywords to identify all controlled trials investigating effects of bupropion alone and combined with naltrexone on the glucose and lipid profile. Pooled weighted mean difference and 95% confidence intervals were achieved by random-effects model. RESULTS: Twelve studies with 5152 participants' were included in this article. The pooled findings showed that bupropion alone or in combination with naltrexone would significantly reduce glucose (weighted mean difference (WMD): -2.25 mg/dL, 95% confidence interval (CI): -4.10, -0.40), insulin (WMD: -4.06 µU/mL, 95% CI: -6.09, -2.03), homeostatic model assessment for insulin resistance (HOMA-IR) (WMD: -0.58, 95% CI: -0.98, -0.19), triglyceride (TG) (WMD: -11.78 mg/dL, 95% CI: -14.48 to -9.08) and increase high-density lipoprotein (HDL) (WMD: 2.68 mg/dL, 95% CI: 2.13 to 3.24). A Greater reduction in glucose levels was observed with duration >26 weeks. Dose of bupropion intake ≤360 mg and intervention for more than 26 weeks decreased insulin level significantly. With regard to lipid profile, reduction of triglycerides is more significant with dose of bupropion greater than 360 mg and a shorter intervention length equal to 26 weeks. CONCLUSIONS: The addition of combination therapies such as bupropion and naltrexone to lifestyle modification can significantly improve glucose metabolism and some lipid parameters.
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Bupropiona , Naltrexona , Humanos , Suplementos Nutricionais , Glucose , Insulina , Naltrexona/farmacologia , TriglicerídeosRESUMO
BACKGROUND: Menopause is associated with elevated cardiovascular risk due to the loss of the cardioprotective effect of oestrogens. Postmenopausal women are often prescribed hormone replacement therapy (HRT) in order to control menopause symptoms and correct hormone imbalances; however, HRT can impact serum lipids' concentrations. At present, data on the effect of the administration of medroxyprogesterone acetate plus conjugated equine oestrogens (MPACEE) on the lipid profile in females are uncertain, as the investigations conducted so far have produced conflicting results. Thus, we aimed to clarify the impact of MPACEE prescription on the serum lipids' values in women by means of a systematic review and meta-analysis of randomized controlled trials (RCTs). METHODS: We employed a random-effects model based on the DerSimonian and Laird method to determine the combined estimates of the intervention's impact on the lipid profile. The computation of the weighted mean difference (WMD) and its corresponding 95% confidence interval (CI) relied on the mean and standard deviation values from both the MPACEE and control group, respectively. RESULTS: A total of 53 RCTs were included in the meta-analysis with 68 RCT arms on total cholesterol (TC), 70 RCT arms on low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG), and 69 RCT arms on high-density lipoprotein cholesterol (HDL-C). Administration of MPACEE resulted in a significant reduction of TC (WMD = -11.93 mg/dL; 95% CI: -13.42, -10.44; p < .001) and LDL-C (WMD = -16.61 mg/dL; 95% CI: -17.97, -15.26; p < .001) levels, and a notable increase in HDL-C (WMD = 3.40 mg/dL; 95% CI: 2.93, 3.86; p < .001) and TG (WMD = 10.28 mg/dL; 95% CI: 7.92, 12.64; p < .001) concentrations. Subgroup analysis revealed that changes in the lipid profile were influenced by several factors: body mass index (for TC, HDL-C, TG), MPACEE dosages (for TC, LDL-C, HDL-C, TG), age (for TC, LDL-C, HDL-C, TG), durations of the intervention (for TC, LDL-C, HDL-C, TG), continuous/sequential administration of MPACEE (continuous for TC; sequential for LDL-C, TG) administration of MPACEE and serum lipids' concentrations before enrolment in the RCT (for TC, LDL-C, HDL-C, TG). CONCLUSIONS: MPACEE administration can influence serum lipids' concentrations in females by raising HDL-C and TG levels and reducing LDL-C and TC values. Therefore, postmenopausal women who suffer from hypercholesterolaemia might benefit from this type of HRT.
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HDL-Colesterol , LDL-Colesterol , Estrogênios Conjugados (USP) , Acetato de Medroxiprogesterona , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos , Feminino , Acetato de Medroxiprogesterona/farmacologia , Acetato de Medroxiprogesterona/administração & dosagem , Humanos , Estrogênios Conjugados (USP)/farmacologia , Estrogênios Conjugados (USP)/administração & dosagem , Triglicerídeos/sangue , HDL-Colesterol/efeitos dos fármacos , HDL-Colesterol/sangue , LDL-Colesterol/efeitos dos fármacos , LDL-Colesterol/sangue , Colesterol/sangue , Lipídeos/sangue , Terapia de Reposição de Estrogênios/métodos , Pós-Menopausa/efeitos dos fármacos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: A large body of literature associated extra virgin olive oil (EVOO) consumption with low risk of cardiovascular disease and mortality. However, findings from clinical trials related to EVOO consumption on blood pressure, lipid profile, and anthropometric and inflammation parameters are not univocal. OBJECTIVES: The aim of this systematic review and meta-analysis was to evaluate the effect of EVOO consumption on cardiometabolic risk factors and inflammatory mediators. METHODS: We searched PubMed/MEDLINE, Scopus, and Cochrane up through 31 March, 2023, without any particular language limitations, in order to identify randomized controlled trials (RCTs) that examined the effects of EVOO consumption on cardiometabolic risk factors, inflammatory mediators, and anthropometric indices. Outcomes were summarized as standardized mean difference (SMD) with 95% confidence intervals (CIs) estimated from Hedge's g and random-effects modeling. Heterogeneity was assessed by Cochran Q-statistic and quantified (I2). RESULTS: Thirty-three trials involving 2020 participants were included. EVOO consumption was associated with a significant decrease in insulin (n = 10; SMD: -0.28; 95% CI: -0.51, -0.05; I2 = 48.57%) and homeostasis model assessment of insulin resistance levels (HOMA-IR) (n = 9; SMD: -0.19; 95% CI: -0.35, -0.03; I2 = 00.00%). This meta-analysis indicated no significant effect of consuming EVOO on fasting blood glucose, triglycerides, total cholesterol, low density lipoproteins, very low density lipoproteins, high density lipoproteins, Apolipoprotein (Apo) A-I and B, lipoprotein a, blood pressure, body mass index, waist circumference, waist to hip ratio, C-reactive protein, interleukin-6, interleukin-10, and tumor necrosis factor α levels (P > 0.05). CONCLUSIONS: The present evidence supports a beneficial effect of EVOO consumption on serum insulin levels and HOMA-IR. However, larger well-designed RCTs are still required to evaluate the effect of EVOO on cardiometabolic risk biomarkers. This study was registered in PROSPERO as CRD42023409125.
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Doenças Cardiovasculares , Insulinas , Humanos , Azeite de Oliva , Ensaios Clínicos Controlados Aleatórios como Assunto , Doenças Cardiovasculares/prevenção & controle , Mediadores da InflamaçãoRESUMO
INTRODUCTION: Neuropeptide Y is a neurotransmitter in the nervous system and belongs to the orexigenic system that increases appetite. Its excessive secretion leads to obesity. Leptin is a pro-inflammatory adipokine (produced in adipose tissue) induced in obesity and may mediate increased antitumor immunity in obesity (including the promotion of M1 macrophages). Leptin and neuropeptide Y gene polymorphisms, causing increased leptin levels and the occurrence of obesity, and lipid profile disorders, may increase the effectiveness of immunotherapy. MATERIALS AND METHODS: In 121 patients with advanced NSCLC without mutations in the EGFR gene and rearrangements of the ALK and ROS1 genes, undergoing immunotherapy (1st and 2nd line of treatment) or chemoimmunotherapy (1st line of treatment), we assessed BMI, lipid profile, PD-L1 expression on cancer cells using the immunohistochemical method (clone SP263 antibody), leptin concentration in blood serum by ELISA, polymorphisms in the promoter region of the genes for leptin (LEP) and neuropeptide Y (NPY) by real-time PCR. RESULTS: Leptin concentration was significantly higher in obese patients than in patients with normal or low weight (p = 0.00003) and in patients with disease stabilization compared to patients with progression observed during immunotherapy (p = 0.012). Disease control occurred significantly more often in patients with the GA or AA genotype than patients with the GG genotype in the rs779039 polymorphism of the LEP gene. The median PFS in the entire study group was five months (95% CI: 3-5.5), and the median OS was 12 months (95% CI: 8-16). Median PFS was highest in patients with TPS ≥ 50% (6.5 months) and in obese patients (6.6 months). Obese patients also had a slightly longer median OS compared to other patients (23.8 vs. 13 months). The multivariate Cox logistic regression test showed that the only factor reducing the risk of progression was TPS ≥ 50% (HR = 0.6068, 95% CI: 0.4001-0.9204, p = 0, 0187), and the only factor reducing the risk of death was high leptin concentration (HR = 0.6743, 95% CI: 0.4243-1.0715, p = 0.0953). CONCLUSION: Assessment of nutritional status, serum leptin concentration and polymorphisms in the LEP gene may be of additional importance in predicting the effectiveness of immunotherapy and chemoimmunotherapy in patients with advanced NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Imunoterapia , Leptina , Neoplasias Pulmonares , Neuropeptídeo Y , Estado Nutricional , Humanos , Leptina/genética , Leptina/sangue , Neuropeptídeo Y/genética , Masculino , Feminino , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/terapia , Pessoa de Meia-Idade , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Imunoterapia/métodos , Idoso , Obesidade/genética , Adulto , Lipídeos/sangue , Polimorfismo Genético , Antígeno B7-H1/genética , Resultado do Tratamento , Idoso de 80 Anos ou maisRESUMO
We examined the lipid profiles in the aqueous humor (AH) of myopic patients to identify differences and investigate the relationships among dissertating lipids. Additionally, we assessed spherical equivalents and axial lengths to explore the pathogenesis of myopia. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was employed to qualitatively and quantitatively analyze the lipid composition of samples from myopic patients with axial lengths <26 mm (Group A) and >28 mm (Group B). Differences in lipid profiles between the two groups were determined using univariate and multivariate analyses. Receiver operator characteristic (ROC) curves were used to identify discriminating lipids. Spearman correlation analysis explored the associations between lipid concentrations and biometric parameters. Three hundred and nine lipids across 21 lipid classes have been identified in this study. Five lipids showed significant differences between Group B and Group A (VIP > 1, P < 0.05): BMP (20:3/22:3), PG (22:1/24:0), PS (14:1/22:4), TG (44:2)_FA18:2, and TG (55:3)_FA18:1. The area under the curve (AUC) for these lipids was >0.75. Notably, the concentrations of BMP (20:3/22:3), PS (14:1/22:4), and TG (55:3)_FA18:1 were correlated with spherical equivalents, while BMP (20:3/22:3) and PS (14:1/22:4) correlated with axial lengths. Our study identified five differential lipids in myopic patients, with three showing significant correlations with the degree of myopia. These findings enhance our understanding of myopia pathogenesis through lipidomic alterations, emphasizing changes in cell membrane composition and function, energy metabolism and storage, and pathways involving inflammation, peroxisome proliferator-activated receptors (PPAR), and metabolic processes related to phosphatidylserine, phosphatidylglycerol, triglycerides, polyunsaturated fatty acids, and cholesterol.
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Maternal hypercholesterolemia (MHC) during pregnancy is associated with the risk of developing aortic lesions in fetuses. There is also a possibility of faster progression of atherosclerosis in offspring born to hypercholesterolemic mothers (HCM) during their adulthood. We investigated whether elevated maternal cholesterol levels during pregnancy influence the lipid levels in offspring. We analyzed the lipid profile of mothers during the three trimesters, cord blood (CB) at birth, and neonatal blood (NB) on Day 2 postpartum in the offspring. Cholesterol levels of HCM significantly increased throughout gestation when compared to normocholesterolemic mothers (NCM). CB lipid levels of newborns of HCM were similar to the newborns of NCM. While NB of offspring of HCM had elevated levels of triglycerides (TG) (p < 0.01) and very low-density lipoprotein (VLDL) (p < 0.01) when compared to the offspring of NCM. MHC also resulted in low newborn birthweight (p < 0.05) and low placental efficiency (ratio of newborn birth weight to placental weight) (p < 0.01) but no change was observed in umbilical cord length or placental weight. Immunohistochemical analysis revealed no significant changes in the protein expression of genes involved in TG metabolisms such as LDLR, VLDLR, CETP, and PPARG. We report that MHC in mothers decreases placental efficiency and newborn birthweight while increasing lipid levels in neonates on the second postpartum day. Given that TG levels modulate the circulating Low-Density lipoproteins, the increase in these levels in neonates gains importance. Whether these consistently high levels cause atherosclerosis in early adulthood warrants further investigation.
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Aterosclerose , Hipercolesterolemia , Recém-Nascido , Gravidez , Humanos , Feminino , Adulto , Peso ao Nascer , Placenta , Lipoproteínas LDL , Colesterol , TriglicerídeosRESUMO
Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most prevalent mitochondrial fatty acid ß-oxidation disorder. In this study, we assessed the variability of the lipid profile in MCADD by analysing plasma samples obtained from 25 children with metabolically controlled MCADD (following a normal diet with frequent feeding and under l-carnitine supplementation) and 21 paediatric control subjects (CT). Gas chromatography-mass spectrometry was employed for the analysis of esterified fatty acids, while high-resolution C18-liquid chromatography-mass spectrometry was used to analyse lipid species. We identified a total of 251 lipid species belonging to 15 distinct lipid classes. Principal component analysis revealed a clear distinction between the MCADD and CT groups. Univariate analysis demonstrated that 126 lipid species exhibited significant differences between the two groups. The lipid species that displayed the most pronounced variations included triacylglycerols and phosphatidylcholines containing saturated and monounsaturated fatty acids, specifically C14:0 and C16:0, which were found to be more abundant in MCADD. The observed changes in the plasma lipidome of children with non-decompensated MCADD suggest an underlying alteration in lipid metabolism. Therefore, longitudinal monitoring and further in-depth investigations are warranted to better understand whether such alterations are specific to MCADD children and their potential long-term impacts.
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Acil-CoA Desidrogenase , Erros Inatos do Metabolismo Lipídico , Lipidômica , Fosfolipídeos , Triglicerídeos , Humanos , Erros Inatos do Metabolismo Lipídico/sangue , Lipidômica/métodos , Criança , Masculino , Feminino , Triglicerídeos/sangue , Fosfolipídeos/sangue , Pré-Escolar , Acil-CoA Desidrogenase/deficiência , Lactente , Adolescente , Metabolismo dos Lipídeos , Estudos de Casos e Controles , Ácidos Graxos/sangue , Ácidos Graxos/metabolismo , Cromatografia Gasosa-Espectrometria de Massas/métodos , Carnitina/sangueRESUMO
Arthritis, a prevalent inflammatory condition, is often linked to obesity as a contributing factor. This study aimed to assess the potential protective effects of purslane extract in male albino rats with induced arthritis and obesity. Fifty rats were randomly assigned to five groups: a control group, an induced arthritis-high-fat diet group, a high-dose purslane extract-supplemented group (300â¯mg/kg body weight) for 8 weeks, a low-dose purslane extract-supplemented group (150â¯mg/kg body weight) for 8 weeks, and a metformin-supplemented group. Arthritis was induced in the rats using Complete Freund's Adjuvant. Plasma biomarkers, including Total Cholesterol, Triglycerides, HDL-cholesterol, LDL-cholesterol, C Reactive Protein (CRP), Erythrocyte Sedimentation Rate (ESR), Rheumatoid Factor (RF), and Anti-CCP, were assessed in each group. The results revealed a significant improvement in these biomarkers in the high-dose purslane-supplemented group (300â¯mg/kg body weight) compared to the induced arthritis-high-fat-diet group. This suggests a potential protective role of purslane against arthritis associated with obesity, likely attributed to its lipolytic capacity and anti-inflammatory properties. These findings contribute to our understanding of the interplay between obesity, arthritis, and natural interventions, providing valuable insights for future therapeutic approaches.
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Artrite Experimental , Obesidade , Extratos Vegetais , Animais , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Masculino , Ratos , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Artrite Experimental/prevenção & controle , Extratos Vegetais/farmacologia , Biomarcadores/sangue , Dieta Hiperlipídica/efeitos adversos , Proteína C-Reativa/metabolismoRESUMO
MicroRNAs (miRNAs) have emerged as important regulators of lipid metabolism. Recent studies have suggested synbiotics may modulate miRNA expression and lipid metabolism. This study aimed to investigate the effects of synbiotic supplementation on circulating miR-27a, miR-33a, and lipid parameters in patients with dyslipidemia. Fifty-six eligible participants were randomly allocated to receive either synbiotic or placebo sachets twice a day for 12 weeks. Each synbiotic sachet contained 3×1010 CFU six species of probiotic microorganisms and 5 grams of inulin and fructooligosaccharide (FOS) as prebiotics. Serum miR-27a and miR-33a expression levels, serum lipids, and apolipoproteins, the fecal concentration of short-chain fatty acids (SCFAs), and Firmicutes and Bacteroidetes phyla were assessed before and after the study. Real-time PCR was used to determine the relative expression levels of miRNAs. The results showed synbiotic supplementation significantly downregulated the expression levels of miR-27a and miR-33a compared to the placebo group (p = 0.008 and p = 0.001, respectively). Furthermore, the intervention group exhibited significant improvements in serum high-density lipoprotein (HDL-C), small dense low-density lipoprotein (sdLDL-C), apoA-I, and apoB-100 (p = 0.008, p = 0.006, p = 0.003, p = 0.001, respectively). The results showed a significant negative correlation between miR-33a expression levels with HDL-C, butyrate, propionate, and a significant positive correlation with total cholesterol (TC), low-density lipoprotein (LDL-C), and sdLDL-C in the intervention group. Fecal bacteria and SCFAs were significantly increased in the intervention group. This study provides evidence that synbiotic supplementation can modulate miR-27a and miR-33a expression and improve lipid metabolism in patients with dyslipidemia.
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BACKGROUND: Vitiligo is an acquired and progressive mucocutaneous disease with the damage of functioning epidermal melanocytes. Metabolic syndrome is associated with inflammatory skin diseases incorporating vitiligo. The circadian dysfunction triggers the pathogenesis of metabolic diseases, so our study aimed to determine the relationship between aryl hydrocarbon receptor nuclear translocator-like gene, a ligand-activated transcription factor and sensor of environmental chemicals, expression and polymorphism with non-segmental vitiligo, as well as its effect on lipid profile. METHODS: This case-control study was handled on 50 non-segmental vitiligo patients (generalized (12) and localized type (focal; 24 and acrofacial; 14)) and 50 matched controls. Each subject was proposed for full history taking, clinical examinations, serum lipid profile, and measurement of BMAL1 gene expression in the blood, and BMAL1 rs2279287 polymorphism of DNA extract from whole blood by real time-PCR. RESULTS: We identified that total cholesterol, triglyceride, and low-density lipoprotein were significantly higher, but high-density lipoprotein was significantly lower in non-segmental vitiligo patients than in the control group. A significant increase in circadian gene expression in non-segmental vitiligo patients was observed, with more detection of the BMAL1 T/C genotype (92%) than the T/T genotype. There was a significant positive relationship between the level of the circadian gene and the vitiligo patient's age, age of onset, and VIDA Score. The level of the circadian gene at Cutoff ≥ 1.16 can predict the prognosis of vitiligo with a sensitivity of 78%, specificity of 84%, and accuracy of 81%. CONCLUSION: The circadian gene has an active role in the progress of non-segmental vitiligo and targeting this gene could have a significant impact on its management.
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Relógios Circadianos , Vitiligo , Humanos , Vitiligo/genética , Fatores de Transcrição ARNTL/genética , Estudos de Casos e Controles , Lipoproteínas HDL , Expressão GênicaRESUMO
PURPOSE: Dyslipidemia is a major health issue worldwide. There is growing interest in understanding the potential role of kimchi consumption on serum lipid profiles. However, there are limited epidemiological studies available on this topic. Therefore, this study aims to investigate the association between kimchi intake and serum lipid profiles. METHODS: We conducted an epidemiological study on participants (aged 40-69 years old) selected from the Health Examinees (HEXA) cohort study (n = 61,761). Four types of kimchi, including Baechu kimchi (cabbage kimchi), Kkakdugi (radish kimchi), Nabak kimchi/Dongchimi (a type of water kimchi made with fermented vegetables), and other kimchi, were assessed by a 106-food item semi-quantitative validated food frequency questionnaire (FFQ). Each kimchi intake is the average value calculated from the FFQ of the baseline and follow-up surveys. Fasting blood data were obtained at baseline and follow-up visits. Linear regression was used to examine the relationship between the intake of kimchi and the change in serum lipid profiles. RESULTS: The mean years between the baseline survey and a follow-up survey was 4.97 years. In this study, compared to the lowest category (< 1 serving/day), Baechu kimchi intake (2- < 3 servings/day) had more negative correlations with the change in values of total cholesterol (ß: -1.600, 95% confidence interval [CI, -2.744, -0.456]), triglycerides (ß: -3.372, 95% CI [-5.414, -1.330]), and low-density lipoprotein cholesterol (ß: -1.155, 95% CI [-2.214, -0.095]) in women. In men, Baechu kimchi intake (2- < 3 servings/day) had a more positive correlation associated with the changes in values of high-density lipoprotein cholesterol (ß: 0.049, 95% CI [0.031, 0.907]) compared to the lowest intake category (< 1 serving/day). CONCLUSIONS: Among Korean adults, consumption of kimchi, particularly Baechu kimchi, was found to be associated with improvements in serum lipid profiles. Further studies are required to conduct additional interventions to confirm the association between kimchi and serum lipid profiles.
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PURPOSE: The original aim of the study was to determine, in a double-blind 3-arm crossover human trial (n = 7), the effect of supplemental levels of iron (25 mg) and zinc (30 mg) on ß-carotene (synthetic) bioavailability (10 h postprandial). However, despite the high dose of supplemental ß-carotene (15 mg) consumed with the high fat (18 g), dairy-based breakfast test meal, there was a negligible postprandial response in plasma and triglyceride rich fraction ß-carotene concentrations. We then systematically investigated the possible reasons for this low bioavailability of ß-carotene. METHODS: We determined (1) if the supplemental ß-carotene could be micellised and absorbed by epithelial cells, using a Caco-2 cell model, (2) if the fat from the test meal was sufficiently bioavailable to facilitate ß-carotene bioavailability, (3) the extent to which the ß-carotene could have been metabolised and converted to retinoic acid/retinol and (4) the effect of the test meal matrix on the ß-carotene bioaccessibility (in vitro digestion) and Caco-2 cellular uptake. RESULTS: We found that (1) The supplemental ß-carotene could be micellised and absorbed by epithelial cells, (2) the postprandial plasma triacylglycerol response was substantial (approximately 75-100 mg dL-1 over 10 h), indicating sufficient lipid bioavailability to ensure ß-carotene absorption, (3) the high fat content of the meal (approximately 18 g) could have resulted in increased ß-carotene metabolism, (4) ß-carotene bioaccessibility from the dairy-based test meal was sixfold lower (p < 0.05) than when digested with olive oil. CONCLUSION: The low ß-carotene bioavailability is probably due to a combination of the metabolism of ß-carotene to retinol by BCMO1 and interactions of ß-carotene with the food matrix, decreasing the bioaccessibility. TRAIL REGISTRATION: The human trail was retrospectively registered (ClinicalTrail.gov ID: NCT05840848).
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PURPOSE: Rheumatoid Arthritis (RA) has a point prevalence of around 20 million people worldwide. Patients with RA often believe that food intake affects disease activity, and that intake of red meat aggravate symptoms. The main objective of the Postprandial Inflammation in Rheumatoid Arthritis (PIRA) trial was to assess whether postprandial inflammation and serum lipid profile are affected differently by a meal including red meat, fatty fish, or a soy protein (vegan) meal. METHODS: Using a randomized controlled crossover design, 25 patients were assigned to eat isocaloric hamburger meals consisting of red meat (60% beef, 40% pork), fatty fish (salmon), or soy protein for breakfast. Blood samples were taken before meals and at intervals up to 5 h postprandial. The analysis included the inflammation marker interleukin 6 (IL-6) and serum lipids. RESULTS: No significant differences in postprandial IL-6 or triglyceride concentrations were found between meals. However, the area under the curve of very low density lipoprotein (VLDL) particle counts, as well as VLDL-4-bound cholesterol, triglycerides, and phospholipids, was higher after the fatty fish compared to both red meat and soy protein. CONCLUSION: Postprandial inflammation assessed by IL-6 did not indicate any acute negative effects of red meat intake compared to fatty fish- or soy protein in patients with RA. The fatty fish meal resulted in a higher number of VLDL-particles and more lipids in the form of small VLDL particles compared to the other protein sources.
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PURPOSE: Cardiovascular disease (CVD) is the primary cause of death worldwide but there is a variation in its burden across some nations that seems to be related to dietary habits. Mediterranean populations have lower rates of morbidity and mortality from CVD. Thus, this systematic review and meta-analysis aimed to assess the impacts of the Mediterranean diet (MedDiet) enriched with olive oil on blood lipids, glycemic indices, blood pressure, and anthropometric indices. METHODS: A comprehensive search of the Web of Science, PubMed (MEDLINE), Scopus, Cochrane Library, Google Scholar, Embase, and CINAHL databases until March 2024 was conducted to identify clinical trials studying the effects of MedDiet enriched with olive oil on the aforementioned parameters. RESULTS: In total, 3303 records were retrieved. A total of 18 clinical trials met the inclusion criteria after records were screened for eligibility. According to the pooled analysis from the random-effects model, the MedDiet enriched with olive oil significantly reduced triglycerides (TG) compared with the control group (WMD = -2.40 mg/dl; 95%CI, -4.533 to -0.262; P = 0.027). Strong heterogeneity was observed. Sensitivity analysis did not change our results and no significant effect of any trial on the overall effect sizes of all variables were found. There was a concern about the reporting bias for some studies which reported some main outcomes. CONCLUSION: MedDiet enriched with olive oil showed no consistent effects on any of the reported markers of cardiovascular health except on TG. SYSTEMATIC REVIEW REGISTRATION: CRD42023424641.
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BACKGROUND: Current recommendations regarding the utility of diagnostic investigations for pediatric hypertension are based on limited evidence, leading to wide practice variation. The objective of this study was to characterize the cohort of children that may benefit from secondary hypertension workup, and determine the diagnostic yield of investigations. METHODS: This was a single-center, retrospective cohort study of 169 children aged 1-18 years referred between 2000 and 2015, to a tertiary pediatric nephrology center in Canada, for evaluation of hypertension. The number of investigations completed, abnormal findings, and diagnostic findings that helped establish hypertension etiology was determined. RESULTS: 56 children were diagnosed with primary and 72 children with secondary hypertension in the outpatient setting. Secondary hypertension was predominant at all ages except for obese adolescents ≥ 12 years. Half of children with traditional risk factors for primary hypertension, including obesity, were diagnosed with secondary hypertension. Kidney ultrasound had the highest yield of diagnostic results (19.8%), with no difference in yield between age groups (P = 0.19). Lipid profile had a high yield of abnormal results (25.4%) as part of cardiovascular risk assessment but was only abnormal in overweight/obese children. Echocardiogram had a high yield for identification of target-organ effects in hypertensive children (33.3%). CONCLUSION: A simplified secondary hypertension workup should be considered for all hypertensive children and adolescents. High yield investigations include a kidney ultrasound, lipid profile for overweight/obese children, and echocardiograms for assessment of target-organ damage. Further testing could be considered based on results of initial investigations for the most cost-effective management. A higher resolution version of the Graphical abstract is available as Supplementary information.
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Hipertensão , Obesidade Infantil , Adolescente , Criança , Humanos , Sobrepeso/complicações , Estudos Retrospectivos , Obesidade Infantil/complicações , Obesidade Infantil/diagnóstico , Hipertensão/diagnóstico , Hipertensão/etiologia , LipídeosRESUMO
AIMS: The aim of this study was to conduct a systematic review and meta-analysis of randomized controlled trials (RCTs) that evaluated the impact of sesame supplementation on body weight (BW), body mass index (BMI), triglycerides (TGs), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), and high-density lipoprotein-cholesterol (HDL-C) in patients with type 2 diabetes mellitus (T2DM). DATA SYNTHESIS: PubMed, Scopus, ISI Web of Science, and Embase were searched without any restrictions until September 2023.Only RCTs reporting the effects of sesame supplementation on body composition and lipid profiles were included, while observational studies and animal models were excluded. The methodological quality of the studies was assessed using the Cochrane risk of bias tool. Out of 997 studies identified, 10 were included in the systematic review and meta-analysis. Our meta-analysis suggested a significant association between sesame supplementation and reduction in TG (weighted mean difference (WMD): -37.61 mg/dl, 95 % CI: -61.48, 13.73), TC (WMD: -32.69 mg/dl, 95 % CI: -47.26, 18.12), and LDL-C (WMD: -28.72 mg/dl, 95 % CI: -44.68, 12.76). However, our meta-analysis indicated that the supplementary intake of sesame had no significant effect on HDL-C, BW, and BMI in patients with T2DM. CONCLUSIONS: This study showed that sesame consumption significantly lowered TG, TC, and LDL-C levels, which may have contributed to the improvement of clinical symptoms in T2DM. However, given the limited number of trials included in the analysis, additional large-scale studies are needed to confirm the effects of sesame consumption on the lipid profile and body composition in patients with T2DM. PROSPERO CODE: CRD42023460630.