From Innate Immunity to Metabolic Disorder: A Review of the NLRP3 Inflammasome in Diabetes Mellitus.

The role of the NLRP3 inflammasome is pivotal in the pathophysiology and progression of diabetes mellitus (DM), encompassing both type 1 (T1D), or type 2 (T2D). As part of the innate immune system, NLRP3 is also responsible for the chronic inflammation triggered by hyperglycemia. In both conditions, NLRP3 facilitates the release of interleukin-1ß and interleukin-18. For T1D, NLRP3 perpetuates the autoimmune cascade, leading to the destruction of pancreatic islet cells. In T2D, its activation is associated with the presence of insulin resistance. NLRP3 activation is also instrumental for the presence of numerous complications associated with DM, microvascular and macrovascular. A considerable number of anti-diabetic drugs have demonstrated the ability to inhibit the NLRP3 inflammasome.

Polyphenol Analysis via LC-MS-ESI and Potent Antioxidant, Anti-Inflammatory, and Antimicrobial Activities of Jatropha multifida L. Extracts Used in Benin Pharmacopoeia.

Jatropha multifida L., a plant from the Euphorbiaceae family, is commonly used in Benin's traditional medicine due to its therapeutic benefits. This study aims to explore the medicinal efficacy of Jatropha multifida L. by evaluating its various biological activities. An initial phytochemical analysis was conducted, following which the polyphenols and flavonoids were quantified and identified using LC-MS-ESI. The antimicrobial efficacy of the extracts was tested using agar diffusion. Their antioxidant capacity was assessed using several methods: DPPH radical reduction, ABTS radical cation reduction, ferric ion (FRAP) reduction, and lipid peroxidation (LPO). Anti-inflammatory activity was determined based on the inhibition of protein (specifically albumin) denaturation. The study identified several phenolic and flavonoid compounds, including 2-Hydroxybenzoic acid, o-Coumaroylquinic acid, Apigenin-apiosyl-glucoside, and luteolin-galactoside. Notably, the extracts of J. multifida demonstrated bactericidal effects against a range of pathogens, with Concentration Minimally Bactericidal (CMB) values ranging from 22.67 mg/mL (for organisms such as S. aureus and C. albicans) to 47.61 mg/mL (for E. coli). Among the extracts, the ethanolic variant displayed the most potent DPPH radical scavenging activity, with an IC50 value of 0.72 ± 0.03 mg/mL. In contrast, the methanolic extract was superior in ferric ion reduction, registering 46.23 ± 1.10 µgEAA/g. Interestingly, the water-ethanolic extract surpassed others in the ABTS reduction method with a score of 0.49 ± 0.11 mol ET/g and also showcased the highest albumin denaturation inhibition rate of 97.31 ± 0.35% at a concentration of 1000 µg/mL. In conclusion, the extracts of Jatropha multifida L. are enriched with bioactive compounds that exhibit significant biological activities, underscoring their therapeutic potential.

Hidradenitis suppurativa. A case report.

Hidradenitis suppurativa is a disease with underestimated incidence, consequences and treatment difficulty. Regarded as a minor illness, for the patient it is disabling physically and socially, and for the doctor it is a challenge in choosing the appropriate treatment. We present the case of a 28-year-old man who presented with an advanced and persistent form of hidradenitis treated in a general surgery department. Solving the case combined conservative and surgical treatment (wide excisions, plasties with fasciocutaneous superior gluteal artery perforator flap, thoracodorsal artery perforator flap, free anterolateral thigh flap). This case illustrates the problems raised by a seemingly trivial disease. KEY WORDS: Fasciocutaneous Superior Gluteal Artery Perforator Flap, Follicular Occlusion, Free Anterolateral Thigh Flap, Hidradenitis Suppurativa, Skin Ulcer, Skin Fold, Thoracodorsal Artery Perforator Flap.

Diagnostic Performance of Extrahepatic Protein Induced by Vitamin K Absence in the Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis.

BACKGROUND AND OBJECTIVES: the early diagnosis of hepatocellular carcinoma (HCC) benefits from the use of alpha-fetoprotein (AFP) together with imaging diagnosis using abdominal ultrasonography, CT, and MRI, leading to improved early detection of HCC. A lot of progress has been made in the field, but some cases are missed or late diagnosed in advanced stages of the disease. Therefore, new tools (serum markers, imagistic technics) are continually being reconsidered. Serum alpha-fetoprotein (AFP), protein induced by vitamin K absence or antagonist II (PIVKA II) diagnostic accuracy for HCC (global and early disease) has been investigated (in a separate or cumulative way). The purpose of the present study was to determine the performance of PIVKA II compared to AFP. MATERIALS AND METHODS: systematic research was conducted in PubMed, Web of Science, Embase, Medline and the Cochrane Central Register of Controlled Trials, taking into consideration articles published between 2018 and 2022. RESULTS: a total number of 37 studies (5037 patients with HCC vs. 8199 patients-control group) have been included in the meta-analysis. PIVKA II presented a better diagnostic accuracy in HCC diagnostic vs. alpha-fetoprotein (global PIVKA II AUROC 0.851 vs. AFP AUROC 0.808, respectively, 0.790 vs. 0.740 in early HCC cases). The conclusion from a clinical point of view, concomitant use of PIVKA II and AFP can bring useful information, added to that brought by ultrasound examination.

Circadian Rhythm and Risk of Hemorrhagic Transformation after Acute Ischemic Stroke Treated with Intravenous Thrombolysis - A Systematic Review.

BACKGROUND: A circadian pattern for the onset of acute ischemic stroke (AIS) has been described, with a higher risk in the early morning and a lower risk during nighttime. However, data assessing the circadian distribution of hemorrhagic transformation after intravenous thrombolysis (ivT) are still incongruent. OBJECTIVES: This review aimed to evaluate whether the time interval based on AIS onset or ivT time could influence the occurrence of intracranial hemorrhage (ICH) related to ivT and if the circadian rhythm of endogenous production of tissue plasminogen activator (t-PA) favors ICH occurrence. METHODS: We conducted a systematic review following the PRISMA guidelines, searching PubMed and Embase for articles in English using the keywords: 'stroke', 'thrombolysis', and 'circadian'. Articles investigating the AIS onset or ivT time effects on circadian variations of ICH in AIS adult patients treated with ivT were included. Based on ICH's incidence and odds ratio, time intervals associated with higher risk and time intervals associated with lower risk were defined. The Newcastle-Ottawa Scale was used to assess the risk of bias. The resulting data were reported in a qualitative narrative synthesis. RESULTS: From the 70 abstracts returned by electronic literature search, six studies with 33,365 patients fulfilled the inclusion criteria, out of which three were retrospective analysis studies, one case-control study, one prospective study, and one post hoc analysis of a multicentre trial. Some studies assessed the relationship between ICH occurrence and circadian rhythm depending on AIS onset time (n = 2), treatment time (n = 2), or both (n = 4). All studies investigated the patients' comorbidities as confounding variables for the circadian pattern of symptomatic ICH (sICH). Two studies found no association between AIS onset or ivT time and patient risk factors, but the other four found several differences and used multivariate logistic regression models to balance these covariates. The overall score of the Newcastle- Ottawa scale was 83.3%, which might be interpreted as overall high quality. CONCLUSION: ICH occurred after ivT seems to follow a circadian pattern; the 18:00-00:00 time frame was the safest one, and patients with AIS onset or ivT time between these hours had the lowest incidence of any ICH, including sICH. The 06:00-12:00 block was associated with the highest incidence of ICH and sICH. However, the analysis is limited by the small number of included studies and the heterogeneous findings reported. Further homogenized studies using comparable time frames and sICH definitions are needed to demonstrate this circadian pattern. The review protocol was registered in the OSF database under reference UHNF, doi:10.17605/OSF.IO/UHNF6.

Bioactive Compounds in Moringa oleifera: Mechanisms of Action, Focus on Their Anti-Inflammatory Properties.

Moringa oleifera (M. oleifera) is a tropical tree native to Pakistan, India, Bangladesh, and Afghanistan; it is cultivated for its nutritious leaves, pods, and seeds. This scientific study was conducted to outline the anti-inflammatory properties and mechanisms of action of bioactive compounds from M. oleifera. The existing research has found that the plant is used in traditional medicine due to its bioactive compounds, including phytochemicals: flavonoids and polyphenols. The compounds are thought to exert their anti-inflammatory effects due to: (1) inhibition of pro-inflammatory enzymes: quercetin and kaempferol inhibit the pro-inflammatory enzymes (cyclooxygenase and lipoxygenase); (2) regulation of cytokine production: isothiocyanates modulate signaling pathways involved in inflammation, such as the nuclear factor-kappa B (NF-kappa B) pathway; isothiocyanates inhibit the production of pro-inflammatory cytokines such as TNF-α (tumor necrosis factor α) and IL-1ß (interleukin-1ß); and (3) antioxidant activity: M. oleifera contains flavonoids, polyphenols, known to reduce oxidative stress and inflammation. The review includes M. oleifera's effects on cardiovascular protection, anti-hypertensive activities, type 2 diabetes, inflammatory bowel disease, and non-alcoholic fatty liver disease (NAFLD). This research could prove valuable for exploring the pharmacological potential of M. oleifera and contributing to the prospects of developing effective medicines for the benefit of human health.

Essential oils from Dysphania genus: Traditional uses, chemical composition, toxicology, and health benefits.

The genus Dysphania belongs to the Amaranthaceae family and is known for its many health benefits. Therefore, it is commonly available worldwide and includes more than 47 species, five species have been mainly reported, and D. ambrosioides has been one of the most widely used plants for thousands of years as a remedy for a wide range of ailments. In recent investigations, the essential oils of the genus Dysphania have been examined for their antibacterial, antioxidant, and antiviral properties related to specific components such as terpenoid compounds that exhibit pharmacological activity. Moreover, some of Dysphania's compounds show a toxicological effect. Therefore, the objective of the study was to provide EO chemical composition and pharmacological data of the genus Dysphania.

Cardiac Toxicity Associated with Immune Checkpoint Inhibitors: A Systematic Review.

Immune checkpoint inhibitors (ICIs) are an important advancement in the field of cancer treatment, significantly improving the survival of patients with a series of advanced malignancies, like melanoma, non-small cell lung cancer (NSCLC), hepatocellular carcinoma (HCC), renal cell carcinoma (RCC), and Hodgkin lymphoma. ICIs act upon T lymphocytes and antigen-presenting cells, targeting programmed cell death protein 1 (PD1), programmed cell death protein ligand 1 (PD-L1), and cytotoxic T-lymphocyte antigen 4 (CTLA-4), breaking the immune tolerance of the T cells against malignant cells and enhancing the body's own immune response. A variety of cardiac-adverse effects are associated with ICI-based treatment, including pericarditis, arrhythmias, cardiomyopathy, and acute coronary syndrome, with myocarditis being the most studied due to its often-unexpected onset and severity. Overall, Myocarditis is rare but presents an immune-related adverse event (irAE) that has a high fatality rate. Considering the rising number of oncological patients treated with ICIs and the severity of their potential adverse effects, a good understanding and continuous investigation of cardiac irAEs is of the utmost importance. This systematic review aimed to revise recent publications (between 2016-2022) on ICI-induced cardiac toxicities and highlight the therapeutical approach and evolution in the selected cases.

Non-Coding RNAs: Prevention, Diagnosis, and Treatment in Myocardial Ischemia-Reperfusion Injury.

Recent knowledge concerning the role of non-coding RNAs (ncRNAs) in myocardial ischemia/reperfusion (I/R) injury provides new insight into their possible roles as specific biomarkers for early diagnosis, prognosis, and treatment. MicroRNAs (miRNAs) have fewer than 200 nucleotides, while long ncRNAs (lncRNAs) have more than 200 nucleotides. The three types of ncRNAs (miRNAs, lncRNAs, and circRNAs) act as signaling molecules strongly involved in cardiovascular disorders (CVD). I/R injury of the heart is the main CVD correlated with acute myocardial infarction (AMI), cardiac surgery, and transplantation. The expression levels of many ncRNAs and miRNAs are highly modified in the plasma of MI patients, and thus they have the potential to diagnose and treat MI. Cardiomyocyte and endothelial cell death is the major trigger for myocardial ischemia-reperfusion syndrome (MIRS). The cardioprotective effect of inflammasome activation in MIRS and the therapeutics targeting the reparative response could prevent progressive post-infarction heart failure. Moreover, the pharmacological and genetic modulation of these ncRNAs has the therapeutic potential to improve clinical outcomes in AMI patients.

Oral Microbiome: Getting to Know and Befriend Neighbors, a Biological Approach.

The oral microbiome, forming a biofilm that covers the oral structures, contains a high number of microorganisms. Biofilm formation starts from the salivary pellicle that allows bacterial adhesion-colonization-proliferation, co-aggregation and biofilm maturation in a complex microbial community. There is a constant bidirectional crosstalk between human host and its oral microbiome. The paper presents the fundamentals regarding the oral microbiome and its relationship to modulator factors, oral and systemic health. The modern studies of oral microorganisms and relationships with the host benefits are based on genomics, transcriptomics, proteomics and metabolomics. Pharmaceuticals such as antimicrobials, prebiotics, probiotics, surface active or abrasive agents and plant-derived ingredients may influence the oral microbiome. Many studies found associations between oral dysbiosis and systemic disorders, including autoimmune diseases, cardiovascular, diabetes, cancers and neurodegenerative disorders. We outline the general and individual factors influencing the host-microbial balance and the possibility to use the analysis of the oral microbiome in prevention, diagnosis and treatment in personalized medicine. Future therapies should take in account the restoration of the normal symbiotic relation with the oral microbiome.

New Insights on the Relationship between Leptin, Ghrelin, and Leptin/Ghrelin Ratio Enforced by Body Mass Index in Obesity and Diabetes.

Currently, adipose tissue is considered an endocrine organ, however, there are still many questions regarding the roles of adipokines-leptin and ghrelin being two adipokines. The purpose of the study was to assess the relationship between the adipokines and their ratio with obesity and diabetes. Methods: Sixty patients (mean age 61.88 ± 10.08) were evaluated. Cardiovascular risk factors, leptin, ghrelin, and insulin resistance score values were assessed. The patients were classified according to their body mass index (BMI) as normal weight, overweight, and obese. Results: 20% normal weight, 51.7% overweight, 28.3% obese, and 23.3% diabetic. Obese patients had higher leptin values (in obese 34,360 pg/mL vs. overweight 18,000 pg/mL vs. normal weight 14,350 pg/mL, p = 0.0049) and leptin/ghrelin ratio (1055 ± 641 vs. 771.36 ± 921 vs. 370.7 ± 257, p = 0.0228). Stratifying the analyses according to the presence of obesity and patients' gender, differences were found for leptin (p = 0.0020 in women, p = 0.0055 in men) and leptin/ghrelin ratio (p = 0.048 in women, p = 0.004 in men). Mean leptin/BMI and leptin/ghrelin/BMI ratios were significantly higher, and the ghrelin/BMI ratio was significantly lower in obese and diabetic patients. In conclusion, obesity and diabetes are associated with changes not only in the total amount but also in the level of adipokines/kg/m2. Changes appear even in overweight subjects, offering a basis for early intervention in diabetic and obese patients.

Diagnostic Performance of Serum Biomarkers Fibroblast Growth Factor 21, Galectin-3 and Copeptin for Heart Failure with Preserved Ejection Fraction in a Sample of Patients with Type 2 Diabetes Mellitus.

More than half of the patients with heart failure have preserved ejection fraction (HFpEF), however evidence shows a mortality rate comparable to those with reduced ejection fraction. The aim of this study was to evaluate whether FGF21, galectin-3 and copeptin can be used as biomarkers to identify HFpEF in patients with confirmed type 2 diabetes mellitus (DM). Sixty-nine diabetic patients were enrolled and divided into two groups: patients with HFpEF (n = 40) and those without HFpEF (n = 29). The ability of the studied biomarkers to discriminate HFpEF cases from non-HFpEF subjects were evaluated by the area under the Receiver Operating Characteristics (ROC) curve and the 95% confidence interval (CI). Compared to patients without heart failure, those with HFpEF had significantly higher levels of FGF21 (mean 146.79 pg/mL vs. 298.98 pg/mL). The AUC value of FGF21 was 0.88, 95% CI: [0.80, 0.96], Se = 85% [70.2, 94.3], Sp = 79.3% [60.3, 92.0], at an optimal cut-off value of 217.40 pg/mL. There was no statistical significance associated with galectin-3 and copeptin between patient cohorts. In conclusion, galectin-3 and copeptin levels were not effective for detecting HFpEF, while FGF21 is a promising biomarker for diagnosing HFpEF in DM patients.

Endothelial Dysfunction, Inflammation, and Oxidative Stress in COVID-19-Mechanisms and Therapeutic Targets.

The outbreak of the COVID-19 pandemic represents an ongoing healthcare emergency responsible for more than 3.4 million deaths worldwide. COVID-19 is the disease caused by SARS-CoV-2, a virus that targets not only the lungs but also the cardiovascular system. COVID-19 can manifest with a wide range of clinical manifestations, from mild symptoms to severe forms of the disease, characterized by respiratory failure due to severe alveolar damage. Several studies investigated the underlying mechanisms of the severe lung damage associated with SARS-CoV-2 infection and revealed that the respiratory failure associated with COVID-19 is the consequence not only of acute respiratory distress syndrome but also of macro- and microvascular involvement. New observations show that COVID-19 is an endothelial disease, and the consequent endotheliopathy is responsible for inflammation, cytokine storm, oxidative stress, and coagulopathy. In this review, we show the central role of endothelial dysfunction, inflammation, and oxidative stress in the COVID-19 pathogenesis and present the therapeutic targets deriving from this endotheliopathy.

Association between polymorphisms of genes involved in the Renin-Angiotensin-Aldosterone System and the adaptive morphological and functional responses to essential hypertension.

Hypertensive cardiac remodeling is illustrated by increased left ventricular (LV) mass index values and/or relative wall thickness (RWT) values >0.42, and functionally by isolated alteration of LV diastole (abnormal relaxation). The aim of the present study was to establish differentiated models of anatomical and functional adaptation to essential hypertension (EHT), in relation to the genetic variants of genes involved in the Renin-Angiotensin-Aldosterone System (RAAS). The M235T-AGT, I/D-ACE, A1166C-R1AngII, A3123C-R2AngII and G83A-REN genotypes were determined using PCR-Restriction Fragment Length Polymorphism in 139 hypertensive subjects. The relationship between the studied RAAS gene polymorphisms with morphological and functional cardiac remodeling was assessed by multiple logistic regression analysis. Patients carrying the C/C, A/C genotypes (A3123C-R2AngII polymorphism) had a 2.72-fold (P=0.033) increased risk of exhibiting an RWT value <0.42; in the multivariate model the risk was 4.02-fold higher (P=0.008). Analysis of LV diastolic dysfunction (LVDD) revealed that hypertensive patients carrying the T/T, M/T genotypes (M235T-AGT polymorphism) had a 2.24-fold (P=0.037) increased risk of developing LVDD and a 2.42-fold increased risk (P=0.039) after adjustment for confounders. Similarly, carriers of the G/G, A/G genotypes (G83A-REN) had a 2.32-fold (P=0.021) increased risk of developing LVDD, and this remained an independent risk factor based on the multivariate model (P=0.033). The results of the present study showed that no particular gene was associated with increased LV mass, but the A3123C-R2AngII polymorphism was associated with a non-concentric type of cardiac response in hypertensive patients. Conversely, the M235T-AGT and G83A-REN polymorphisms were found to be statistically significantly associated with LVDD when assessing abnormal relaxation.

IL27 T4730C Polymorphism and Serology in Multiple Sclerosis: A Pilot Study.

BACKGROUND: Multiple sclerosis (MS) is one of the most debilitating neurological diseases of young adults. The presence of a single nucleotide polymorphism in the promoter regions of the interleukin 27 gene (IL27 T4730C, rs181206) may alter the transcription and the production of cytokine levels, leading to MS. PATIENTS AND METHODS: We performed a case-control study including 82 individuals: 51 patients diagnosed with MS and 31 healthy controls. Polymerase chain reaction-restriction fragment length polymorphism was used in order to determine the genotypes for the IL27 T4730С polymorphism and enzyme-linked immunosorbent assay to measure the serum IL27 level. RESULTS: Carriers of the T4730С polymorphism were found to have a 6-fold [95% confidence intervaI (CI)=1.83-19.63, p=0.002] increased risk for MS. Univariate logistic regression analysis showed an increased frequency of the TC4730 heterozygous genotype (39.2% vs. 9.7%) and also of the C4730 allele (27.45% vs. 8.06) in patients compared to controls, with a 6.02-fold increased risk (95% CI=1.61-22.46, p=0.006) and a 4.31-fold increased risk (95% CI=1.57-11.87, p=0.002) of developing MS. IL27 levels were significantly lower in patients compared to controls (12.35 versus 14.34 pg/ml, p=0.039), without significant differences between genotypes. Multivariate logistic analysis showed that IL27 T4730C polymorphism (odds ratio=6.272, 95% CI=1.84-21.40, p=0.003) and smoking (odds ratio=4.214, 95% CI=1.39-12.74, p=0.011) represented independent risk factors for MS. CONCLUSION: Our study provides a possible link between IL27 level and IL27 T4730C gene polymorphism and the risk for developing MS in a Romanian population.

MicroRNAs: The Link between the Metabolic Syndrome and Oncogenesis.

Metabolic syndrome (MetS) represents a cluster of disorders that increase the risk of a plethora of conditions, in particular type two diabetes, cardiovascular diseases, and certain types of cancers. MetS is a complex entity characterized by a chronic inflammatory state that implies dysregulations of adipokins and proinflammatory cytokins together with hormonal and growth factors imbalances. Of great interest is the implication of microRNA (miRNA, miR), non-coding RNA, in cancer genesis, progression, and metastasis. The adipose tissue serves as an important source of miRs, which represent a novel class of adipokines, that play a crucial role in carcinogenesis. Altered miRs secretion in the adipose tissue, in the context of MetS, might explain their implication in the oncogenesis. The interplay between miRs expressed in adipose tissue, their dysregulation and cancer pathogenesis are still intriguing, taking into consideration the fact that miRNAs show both carcinogenic and tumor suppressor effects. The aim of our review was to discuss the latest publications concerning the implication of miRs dysregulation in MetS and their significance in tumoral signaling pathways. Furthermore, we emphasized the role of miRNAs as potential target therapies and their implication in cancer progression and metastasis.

Assessment of subclinical diabetic cardiomyopathy by speckle-tracking imaging.

BACKGROUND: Diastolic dysfunction is traditionally believed to be the first subclinical manifestation of diabetic cardiomyopathy (DCM), leading to systolic dysfunction and then overt heart failure. However, in the last few years, several studies suggested that systolic subclinical dysfunction measured by speckle-tracking echocardiography (STE) may appear ahead of diastolic dysfunction. In this review, the main endpoint is to show whether subclinical myocardial systolic dysfunction appears ahead of diastolic dysfunction and the implication this may have on the evolution and management of DCM. MATERIALS AND METHODS: We performed a search in PubMed for all relevant publications on the assessment of DCM by STE from 1 June 2015 to 1 June 2020. RESULTS AND CONCLUSIONS: The results illustrate that subclinical systolic dysfunction assessed by STE is present in early DCM stages, with or without the association of diastolic dysfunction. This could be a promising perspective for the early management of patients with DCM leading to the prevention of the overt form of disease.

The Impact of Obesity on Left Ventricular Hypertrophy and Diastolic Function in Caucasian Children.

Background: Left ventricular hypertrophy (LVH) and diastolic dysfunction are correlated with obesity and hypertension in adult patients, but few studies have investigated the association between obesity itself and left ventricular function in children. The aim of this study was to evaluate the effect of obesity and LVH on left ventricular diastolic function in pediatric subjects compared with children without obesity. Methods: A number of 454 patients from an outpatient cardiology service were enrolled in a prospective study, 33 children with obesity, 20 overweight children, and 401 children without obesity. The subjects were assigned to three groups according to age and school grade. A standardized two-dimensional echocardiography analysis was performed in all children. The evaluated echocardiographic parameters included thickness of the interventricular septum (IVS), thickness of the posterior wall of the left ventricle, and left atrium size. The left ventricular diastolic function was analyzed by the classic pulsed-wave Doppler technique, tissue Doppler technique, and continuous Doppler technique. Results: The number of children with obesity was higher in the school and adolescent groups. The median age of children with obesity was 9 years. The subjects were classified according to blood pressure values in hypertensive, with high-normal blood pressure/prehypertension and with normal blood pressure values. Standard echocardiography showed that children with obesity had significantly increased thickness of the IVS and of the posterior wall compared with nonobesity subjects (P < 0.001). Left ventricular systolic function was preserved in both groups. Diastolic function was normal in the obesity group and in the non-obesity group, respectively. Conclusions: The results of this study demonstrate that childhood obesity is associated with significant changes in the myocardial structure consisting of LVH, but we did not find an early alteration in the left ventricular diastolic function of the subjects with obesity compared with patients with a normal weight.

Potential Contribution of IL-27 and IL-23 Gene Polymorphisms to Multiple Sclerosis Susceptibility: An Association Analysis at Genotype and Haplotype Level.

(1) Background: interleukin 23 (IL-23) and interleukin 27 (IL-27) modulate the activity of T helper 17 cells (Th17) with critical roles in autoimmune diseases and multiple sclerosis (MS). The genes responsible for cytokine generation are highly influenced by the presence of single nucleotide polymorphisms (SNP) in main regions such as regulatory sequences or in promoter regions, contributing to disease susceptibility and evolution. The present study analyzed the associations of IL-23 and IL-27 SNPs with susceptibility to multiple sclerosis. (2) Methods: We performed a case-control study including 252 subjects: 157 patients diagnosed with MS and 95 controls. We used polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) to determine the genotypes for IL-27 T4730C (rs 181206), IL-27 A964G (rs 153109), and IL-23 receptor gene (IL-23R) G1142A (rs 11209026). (3) Results: The IL27-T4730C gene polymorphism was significantly associated with an increased odds of MS under the dominant genetic model (TC + CC variant genotypes, adjusted odds ratio OR = 4.06, 95% CI: 2.14-7.83, p-value = 0.000007, Q-value = 0.000063). Individuals carrying the IL-27 A924G variant (AG + GG) genotype presented higher odds of MS compared to non-carriers under the dominant model (adjusted OR = 1.93, 95% CI: 1.05-3.51, p-value = 0.0324, Q-value = 0.05832) and the allelic genetic model (unadjusted p-value = 0.015, OR = 1.58, 95% CI: 1.09-2.28), while IL-23-R381Q SNP conferred a decreased odds of MS under a codominant model of inheritance (adjusted OR = 0.26, 95% CI: 0.08-0.92, p-value = 0.0276, Q-value = 0.058) and an allelic model (unadjusted p-value = 0.008, OR = 0.23, 95% CI: 0.07-0.75). In an additive model with adjustment for age group (≤40 years vs. >40 years), sex and smoking, patients carrying the G-C (A964G, T4730C) haplotype had a 3.18 increased risk (95% CI: 1.74-5.81, p < 0.001) to develop multiple sclerosis. (4) Conclusions: The results of the current study showed a significant relationship of IL-27-A964G and IL-27-T4730C polymorphisms with increased risk of MS, and also the protective role of the IL-23-R381Q polymorphism. Moreover, the haplotype-based analysis proposed the mutant G-C (A924G, T4730C) as a significant risk haplotype for the development of MS.

Association Between M235T-AGT and I/D-ACE Polymorphisms and Carotid Atheromatosis in Hypertensive Patients: A Cross-Sectional Study.

BACKGROUND/AIM: The renin-angiotensin-aldosterone system (RAAS) may be implicated in carotid atheromatosis (CA) development. We aimed to assess the relationship of M235T-angiotensinogen (AGT) and insertion/deletion of angiotensin conversion enzyme (I/D-ACE) genotypes with CA in patients with essential hypertension (EHT). PATIENTS AND METHODS: We determined the M235T-AGT and I/D-ACE genotypes, using PCR-RFLP methods, in 162 hypertensive subjects from three tertiary regional medical centers. The relationship between the studied RAAS gene polymorphisms and CA was assessed by multiple logistic regressions. RESULTS: Hypertensive patients carrying the MT/TT235-AGT and MT235-AGT genotypes had a 2.17-fold (p=0.033) and 2.24-fold (p=0.036) increased risk to develop CA, respectively. These genotypes, MT/TT 235-AGT (OR=2.17, p=0.033) and MT235-AGT (OR=2.24, p=0.036), remain independent risk factors for CA in hypertensive patients according to the multivariate model. CONCLUSION: There is a statistically significant association between M235T-AGT and CA, when adjusting for several confounders and controlling for hypertension.