In response to a perceived epidemic of coronary heart disease, Ancel Keys introduced the lipid-heart hypothesis in 1953 which asserted that high intakes of total fat, saturated fat, and cholesterol lead to atherosclerosis and that consuming less fat and cholesterol, and replacing saturated fat with polyunsaturated fat, would reduce serum cholesterol and consequently the risk of heart disease. Keys proposed an equation that would predict the concentration of serum cholesterol (DChol.) from consumption of saturated fat (DS), polyunsaturated fat (DP), and cholesterol (DZ): ΔChol. = 1.2(2ΔS − ΔP) + 1.5ΔZ. However, the Keys equation conflated natural saturated fat and industrial trans-fat into a single parameter and considered only linoleic acid as the polyunsaturated fat. This ignored the widespread consumption of trans-fat and its effects on serum cholesterol and promoted an imbalance of omega-6 to omega-3 fatty acids in the diet. Numerous observational, epidemiological, interventional, and autopsy studies have failed to validate the Keys equation and the lipid-heart hypothesis. Nevertheless, these have been the cornerstone of national and international dietary guidelines which have focused disproportionately on heart disease and much less so on cancer and metabolic disorders, which have steadily increased since the adoption of this hypothesis.

Turner syndrome (TS) is a chromosomal disorder that is caused by a missing or structurally ab-normal second sex chromosome. Subjects with TS are at an increased risk of developing intrauterine growth retardation, low birth weight, short stature, congenital heart diseases, infertility, obesity, dyslipidemia, hypertension, insulin resistance, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular diseases (stroke and myocardial infarction). The underlying pathogenetic mechanism of TS is unknown. The assumption that X chromosome-linked gene haploinsufficiency is associated with the TS phenotype is questioned since such genes have not been identified. Thus, other pathogenic mechanisms have been suggested to explain this phenotype. Morphogenesis encompasses a series of events that includes cell division, the production of migratory precursors and their progeny, differentiation, programmed cell death, and integration into organs and systems. The precise control of the growth and differentiation of cells is essential for normal development. The cell cycle frequency and the number of proliferating cells are essential in cell growth. 45,X cells have a failure to proliferate at a normal rate, leading to a decreased cell number in a given tissue during organogenesis. A convergence of data indicates an association between a prolonged cell cycle and the phenotypical features in Turner syndrome. This review aims to examine old and new findings concerning the relationship between a prolonged cell cycle and TS phenotype. These studies reveal a diversity of phenotypic features in TS that could be explained by reduced cell proliferation. The implications of this hypothesis for our understanding of the TS phenotype and its pathogenesis are discussed. It is not surprising that 45,X monosomy leads to cellular growth pathway dysregulation with profound deleterious effects on both embryonic and later stages of development. The prolonged cell cycle could represent the beginning of the pathogenesis of TS, leading to a series of phenotypic consequences in embryonic/fetal, neonatal, pediatric, adolescence, and adulthood life.

We evaluated the usefulness of the novel cholesterol-triglyceride subgroup (CTS) indices that potentially reflect the metabolic status regarding risk of coronary heart disease (CHD) using a retrospective longitudinal study of the Japanese general population. We recruited 12,373 individuals from the annual users of our healthcare center. Among them, the first onset of CHD was recorded in 131 individuals between April, 2014 and March, 2020. The multivariate Cox proportional hazards regression analyses for all normalized lipid indices revealed that the CTSqnt index showed a comparable hazard ratio for the CHD outcome to non-high-density lipoprotein cholesterol (nonHDL-c) and triglycerides. The HR of the CTSqlt index was significantly lower than for CTSqnt, but still comparable to that for low-density lipoprotein cholesterol (LDL-c). In comparison with the other indices, CTSqlt is more sensitive to risk increment while the index value increases. Linear regression analyses for the CTS indices and previously known lipid indices suggest that the CTSqnt and CTSqlt indices reflect the quantity of atherogenic lipoproteins and size of smaller and denser LDLs, respectively. Furthermore, the CTSqnt/HDL-c index can be used as a comprehensive risk indicator that may represent the status of lipid metabolism determined by the CTSqlt and CTSqnt indices and thus may be useful for screening. The CTS indices can be used to evaluate the metabolic status of individuals, which may increase the risk of future CHD.

Thyroid hormones, their metabolites and synthetic analogues are potential anti-steatotic drug candidates considering that subclinical and manifest hypothyroidism is associated with hepatic lipid accumulation, non-alcoholic fatty liver disease, and its pandemic sequelae. Thyromimetically active compounds stimulate hepatic lipogenesis, fatty acid beta-oxidation, cholesterol metabolism and metabolic pathways of glucose homeostasis. Many of these effects are mediated by T3 receptor β1-dependent modulation of transcription. However, rapid non-canonical mitochondrial effects have also been reported, especially for the metabolite 3,5-diiodothyronine (3,5-T2), which does not elicit the full spectrum of “thyromimetic” actions inherent to T3. Most preclinical studies in rodent models of obesity and first human clinical trials are promising with respect to the antisteatotic hepatic effects, but potent agents exhibit unwanted thyromimetic effects on the heart and/or suppress feedback regulation of the hypothalamus-pituitary-thyroid-periphery axis and the fine-tuned thyroid hormone system. This review focusses on 3,5-T2 effects on hepatic lipid and glucose metabolism and (non-)canonical mechanisms of action including its mitochondrial targets. Various high fat diet animal models with distinct thyroid hormone status indicate species- and dose-dependent efficiency of 3,5-T2 and its synthetic analogue TRC150094. No convincing evidence has been presented for their clinical use in prevention or treatment of obesity and related metabolic conditions.

Amyloidosis is due to deposition of an excessive amount of protein in many parenchymal tissues, including myocardium. The onset of cardiac Amyloidosis (CA) is an inauspicious prognostic factor, that can lead to sudden death. We retrospectively analyzed 135 patients with systemic amyloidosis, admitted to our ward between 1981 and 2019. Among them, 54 patients (46.30% F / 53.70% M, age 63.95±12.82 years) presented CA at baseline. In 53 patients, there was associated with multiorgan involvement, while in one there was primary myocardial deposition. As control group, we enrolled 81 patients (49.30% F / 50.70% M, aged 58.33±15.65) who did not meet the criteria for CA. In 44/54 of patients CA was associated with AL, 5/54 with AA, 3/54 of patients with ATTR, in 1/54 AL was related to hemodialysis and 1/54 to Gel-Amyloidosis. The most common AL type was IgG (28/44); less frequent forms were either IgA (7/40) or IgD (2/40), while seven patients had a λ free light chain form. The 32 AL with complete Ig were 31 λ-chain and just one k-chain. CA patients presented normal BP (SBP 118.0±8.4 mmHg; DBP 73.8±4.9 mmHg), while those with nCA had increased proteinuria (p=0.02). TnI and NT-proBNP were significantly increased compared to nCA (p= 0.031 and p=0.047, respectively). In CA patients we found an increased LDH compared to nCA (p=0.0011). CA patients were also found to have an increased interventricular septum thickness compared to nCA (p=0.002), a decreased Ejection Fraction % (p=0.0018) and Doppler velocity E/e’ ratio (p=0.0095). Moreover, CA patients were seen to have an enhanced right atrium area (p=0.0179), right ventricle basal diameter (p= 0.0112) and wall thickness (p=0.0471) as compared to nCA, as well as an increased inferior cava vein diameter (p=0.0495). TAPSE was the method chosen to evaluate systolic function of the right heart. In CA subjects very poor TAPSE levels were found compared to nCA patients (p=0.0495). Additionally, we found a significant positive correlation between TAPSE and lymphocyte count (r=0.47; p=0.031) as well as Gamma globulins (r=0.43, p=0.033), Monoclonal component (r=0.72; p=0.047) and IgG values (r=0.62, p=0.018). On the contrary, a significant negative correlation with LDH (r=-0.57, p=0.005), IVS (r=-0.51, p=0.008) and diastolic function evaluated as E/e’ (r=-0.60, p=0.003) were verified. CA patients had very poor survival compared to controls (30 vs. 66 months in CA vs nCA, respectively, P=0.15). Mean survival of CA individuals was worse also when stratified according to NT-proBNP levels, using 2500 pg/mL as class boundary (174 vs. 5.5 months, for patients with lower vs higher values than the median, respectively p=0.013). In much the same way, decreased right heart systolic function was correlated with a worse prognosis (18.0 months median survival, not reached in subjects with lower values than 18mm, p=0.0186). Finally, our data highlight the potential prognostic and predictive value of right heart alterations characterizing amyloidosis, as a novel clinical parameter correlated to increased LDH and immunoglobulins levels. Overall, we confirm the clinical relevance of cardiac involvement and propose that right heart evaluation may be considered as a new marker for clinical risk stratification in patients with amyloidosis.

The present study examined and compared the effects of high- and low-molecular weight (MW) chitosan, a nutraceutical, on intestinal and liver lipid metabolism in rats fed with high-fat diet. Both high- and low-MW chitosan decreased liver weight, elongated small intestine, improved the dysregulation of blood lipids and liver fat accumulation, and increased fecal lipid excretion in high-fat diet-fed rats. Supplementation of both high- and low-MW chitosan significantly inhibited the decreased phosphorylated AMP-activated protein kinase (AMPK)α and peroxisome proliferator-activated receptor (PPAR)α protein expressions and the increased lipogenesis/cholesterogenesis-associated protein expressions (sterol regulatory element binding protein (SREBP)1c, SREBP2, and PPARγ) and the decreased apolipoprotein (Apo)E and microsomal triglyceride transfer protein (MTTP) protein expressions in the livers of high-fat diet-fed rats. Both high and low-MW chitosan supplementation could also suppress the increased MTTP protein expression and the decreased angiopoietin-like protein (Angptl)4 protein expression in the intestines of high-fat diet-fed rats. Comparison between high and low-MW chitosan, high-MW chitosan has a higher efficiency than low-MW chitosan on the inhibition of intestinal lipid absorption and the increase of hepatic fatty acid oxidation, which can improve liver lipid biosynthesis and accumulation.

Biological membranes are fascinating. Santiago Ramón y Cajal, who received the Nobel prize in 1906 together with Camillo Golgi for their work on the nervous system, wrote “[..]in the study of this membrane[..] I felt more profoundly than in any other subject of study the shuddering sensation of the unfathomable mystery of life”[1]. The visualization and conceptualization of these biological objects have profoundly shaped many aspects of modern biology, drawing inspiration from experiments, computer simulations, as well as from the imagination of scientists and artists. The aim of this review is to provide a fresh look on current ideas of biological membrane organization and dynamics by discussing selected examples across fields [1] The full quotation is “I must not conceal the fact that in the study of this membrane I for the first time felt my faith in Darwinism (hypothesis of natural selection) weakened, being amazed and confounded by the supreme constructive ingenuity revealed not only in the retina and in the dioptric apparatus of the vertebrates but even in the meanest insect eye. There, in fine, I felt more profoundly than in any other subject of study the shuddering sensation of the unfathomable mystery of life.” from the autobiography Recollections of My Life.

Hyperlipidemia case was described as a rise of lipid profile or lipoproteins in the blood. This study describe briefly investigate the reducing hyperlipideamia impact of Ginkgo biloba on the level of lipid profile.

Giant unilamellar vesicles (GUVs) are membrane model used to study membrane properties. Electroformation is one of the methods used to produce GUVs. During electroformation protocol dry lipid film is formed. Drying of the lipid film induce Cholesterol (Chol) demixing artifact, in which Chol forms anhydrous crystals, where these crystals does not participate in formation of vesicles. This leads to a lower Chol concentration in the vesicle bilayers compared to the Chol concentration in the initial lipid solution. To address this problem, we propose novel electroformation protocol that includes rapid solvent exchange, plasma cleaning and spin-coating methods to produce GUVs. We tested the protocol focusing on vesicles with high Chol content using different spin-coating durations and vesicle types deposition. Additionally, we compared the novel protocol using completely dry lipid film. The optimal spin-coating duration for vesicles made out of phosphatidylcholine/Chol mixture was 30 s. Mulitlamellar vesicles (MLVs), large unilamellar vesicles (LUVs) obtained by extrusion of MLVs through 100 nm membrane pores and LUVs obtained by extrusion of previously obtained LUVs through 50 nm membrane pores were deposited on electrode for 1.5/1 Chol/phosphatidylcholine lipid mixture and the results were compared. Electroformation using all three deposited vesicle types gave a high GUVs yield, but deposition of LUVs obtained by extrusion of MLVs through 100 nm membrane pores gave the most reproducible results. Using deposition of these LUVs, we produced GUVs with high yield for 6 different Chol concentrations (from 0 % to 71.4%). Using protocol that includes dry lipid film GUVs yield was lower and Chol demixing artifact was induced, proving that the lipid film should never undergo drying when Chol content is high.

Right atrial isomerism (RAI) is a complex entity whose treatment and outcome are heterogeneous. The aim of this study was to analyze the results obtained after cardiac surgery in patients with RAI. A retrospective study was conducted; it included patients diagnosed with RAI who underwent cardiac surgery; their follow-up was from January 1, 2010 to March 31, 2020. Demographic characteristics and perioperative conditions were described. Thirty-eight patients with RAI were included, the median age was 4 years (IQR 2-9.2), and 57.9% were men. The main diagnoses were atrioventricular canal (63.2%) and pulmonary stenosis (55.3%). The most common surgical procedures were modified Blalock‐Taussig shunt (65.8%) and total cavopulmonary connection with an extracardiac conduit fenestrated without cardiopulmonary bypass (15.9%). The use of inhaled nitric oxide was a marker of postoperative mortality in critically ill patients (OR: 10.33; 95% CI: 1.04 - 102.08; p = 0.02). The overall survival was 86.8%, with a better outcome in those who did not require reintubation (Log Rank, p < 0.01). The survival of RAI was similar to other centers of reference. Individuals with RAI should be evaluated rigorously to determine an adequate repair strategy, considering high morbidity and mortality.

Background: Limited research has explored sex-specific differences in death predictors of HF pa-tients with ischemic (iCMP) and nonischemic (niCMP) cardiomyopathy. This study assessed sex differences in niCMP and iCMP prognosis. Methods: We studied 7,487 patients with HF between February 2017 and September 2020. Clini-cal features and echocardiographic findings were collected. We used Kaplan-Meier, Cox propor-tional hazards models, and score chi-square of Cox regression to determine death predictors in women and men. Results: mean age was 64.3±14.2 years, with 4,417 (59%) males. Women with iCMP and niCMP exhibited significantly higher mean age, higher mean left ventricular ejection fraction, and smaller left ventricular diastolic diameter than men. Over 2.26 years of follow-up, 325 (14.7%) women and 420 (15.7%) men, and 211 women (24.5%) and 519 men (29.8%) died in niCMP (p=NS) and iCMP (p=0.004), respectively. Cumulative incidence of death was higher in men with iCMP (log-rank p<0.0001) but similar in niCMP. Cox regression showed chronic kidney disease, dia-betes, stroke, atrial fibrillation, age, and myocardial infarction, as main predictors of death for iCMP in women and men. Conclusion: Women exhibited a better prognosis than men in iCMP, but similar for niCMP. Nevertheless, sex was not an independent predictor of death for both CMP.

This study investigated modifications in the ubiquitin proteasome system (UPS) in a mouse model of type 2 diabetes mellitus (T2DM) and their relationship to heart complications. db/db mice heart tissues were compared with WT mice tissues using RNA sequencing, qRT-PCR, and protein analysis to identify cardiac UPS modifications associated with diabetes. The findings unveiled a distinctive gene profile in the hearts of db/db mice with decreased levels of nppb mRNA and increased levels of Myh7, indicating potential cardiac dysfunction. mRNA levels of USP18 (deubiquitinating enzyme), psmb8, and psmb9 (proteasome β-subunits) were downregulated in db/db mice while mRNA levels of RNF167 (E3 ligase) were increased. Corresponding LMP2 and LMP7 proteins were downregulated in db/db mice, and RNF167 was elevated in Adult diabetic mice. Reduced expression of LMP2 and LMP7, along with increased RNF167 expression, may contribute to future cardiac deterioration commonly observed in diabetes. This study enhances our understanding of UPS imbalances in the hearts of diabetic mice and raises questions about the interplay between the UPS and other cellular processes, such as autophagy. Further exploration in this area could provide valuable insights into the mechanisms underlying diabetic heart complications and potential therapeutic targets.

The thyroid-heart relationship has a long and articulated history of its own, a history that en-compasses physiological and pathophysiological knowledge, the latter particularly in the context of cardiac diseases such as heart failure, arrhythmias and ischaemic heart disease. In recent years, molecular biology studies, in an experimental context, have highlighted the extraordinary dialogue that exists among the two systems in the field of cardioprotection, being an extremely important area for the treatment of cardiac diseases in both acute and chronic phases. In addi-tion, in the last few years, several studies have been carried out on the prognostic impact of al-terations in thyroid function, including subclinical ones, in heart disease, in particular in heart failure and acute myocardial infarction, with evidence of a negative prognostic impact of these and therefore with the suggestion to treat these alterations in order to prevent cardiac events, such as death. This review provides a comprehensive summary of the heart-thyroid relation-ship.

Objective: The aim of this study is to explore what inside the lipid lump obtained from skin. Try to understand the reasons for these physiological functions. In this paper, the lipid droplets or lumps was aimed to shed light on, figuring out what kind of cracks from metabolism were embedded inside. Results: A novel method was introduced for the detection of pathogens within lipid droplets extracted from acne or inflamed pores, as well as normal pores, using microscopic analysis. Through this technique, the presence of cracks from our body within these lipid droplets were identified. Methods: Observations were conducted using a microscope, with samples placed on slides and grind like blood smear. To enhance the transparency of the samples, tween-20 was utilized. This reagent was first time to be used for observing such big lipid lump of skin secretion. The evidences were recorded using the DMi8 camera from Leica.

The endothelium is a monolayer of cells lining the inner blood vessels. Endothelial cells (ECs) play indispensable roles in angiogenesis, homeostasis, and immune response under normal physiological conditions, and their dysfunction is closely associated with pathologies such as cardiovascular diseases. Abnormal EC metabolism, especially fatty acid (FA) dysfunctional metabolism, contributes to the development of many diseases including pulmonary hypertension (PH). In this review, we focus on discussing the latest advances in FA metabolism in ECs under normal and pathological conditions with an emphasis on PH. We also highlight areas of research that warrant further investigation.

Magnetosomes of magnetotactic bacteria consist of magnetic nanocrystals with defined morphologies enclosed in vesicles originated from cytoplasmic membrane invaginations. Although many proteins are involved in creating magnetosomes, a single magnetosome protein, Mms6, can direct the crystallization of magnetite nanoparticles in vitro. The in vivo role of Mms6 in magnetosome formation is debated and the observation that Mms6 binds ferric and not ferrous iron raises the question of how Mms6 could promote the crystallization of magnetite, which contains both ferric and ferrous iron. Here we show that Mms6 is a ferric reductase that reduces ferric to ferrous iron using NADH and FAD as electron donor and cofactor, respectively. Reductase activity is elevated when Mms6 is integrated into either liposomes or bicelles. Analysis of Mms6 mutants suggests that the C-terminal domain binds iron and the N-terminal domain contains the catalytic site. Although Mms6 forms multimers that involve C-terminal and N-terminal domain interactions, a fusion protein with Mms6, which remains a monomer, displays reductase activity, which suggests that the catalytic site is fully in the monomer. These results are consistent with a hypothesis that Mms6, a membrane protein, promotes the formation of magnetite by a mechanism that involves reducing iron.

Laminopathies are a spectrum of diseases caused by LMNA mutations. In familial partial lipodystrophy of Dunnigan (FPLD), LMNA plays role in the differentiation and development of adipocytes and lipid metabolism. Changes in LMNA predict not only the differentiation of adipose-derived mesenchymal stem cells (AD-MSCs) but also the transformation of cancer cells. Hence, our in-depth study aimed to identify the molecular connection between disordered lipid metabolism and hepatic carcinogenesis. We first discovered significant positive correlations between pLMNA and two key rate-limiting enzymes in de novo fatty acid synthesis, acetyl-CoA-carboxylase 1 (ACC1) and fatty acid synthase (FASN), in the liver tissue but not in adipose tissue of obese model rats. Moreover, LMNA knockdown (KD) in rat AD-MSCs prevented the differentiation and maturation of adipocytes. To clarify the mechanistic relationship with lipogenesis, gain- and loss-of-function experiments in which functional changes and the related molecular pathways were investigated in a normal hepatocyte line (7701 cells). Adenosine 5'-monophosphate activated protein kinase α (AMPKα) was found to be activated by abnormalities in the LMNA structure under conditions of LMNA deletion, farnesyltransferase inhibitor (FTI) treatment and LMNA mutations associated with clinical FPLD pathogenic phenotype. Active AMPKα could directly phosphorylate ACC1 and thus inhibit lipid synthesis but induced glycolysis in both HCC cells and normal cells. The HCC cells could not survive with LMNA knockout (KO) or even KD. Lonafarnib (an FTI) combined with low-glucose conditions significantly decreased the proliferation of HepG2 and MHCC cells by inhibiting glycolysis and the maturation of prelamin A.

A reliable and practical renal-lipid quantification and imaging method is needed. Here, the feasibility of an accelerated MRSI method to map renal fat fractions (FF) at 3T and its repeatability were investigated. A 2D density-weighted concentric-ring-trajectory MRSI was used to accelerate acquiring 48×48 voxels (each of 0.25 ml spatial-resolution) without respiratory navigation implementations. The data was collected over 512 complex-FID timepoints with a 1250 Hz spectral bandwidth. The MRSI sequence was designed with a metabolite-cycling technique for lipid-water separation. The in vivo repeatability performance of the sequence was assessed by conducting a test-reposition-retest study within healthy subjects. The coefficient of variation (CV) in the estimated FF from the test-retest measurements showed a high degree of repeatability of the MRSI-FF (CV= 4.3 ±2.5%). Additionally, the matching level of spectral signature within the same anatomical region was also investigated, and their intrasubject repeatability was also high, with a small standard deviation (8.1 ±6.4%). The MRSI acquisition duration was ~3 minutes only. The proposed MRSI technique can be a reliable technique to quantify and map renal metabolites within a clinically acceptable scan time at 3T that supports the future application of this technique for the non-invasive characterization of heterogeneous renal diseases and tumors.

Microalgae are recognized as a third generation feedstock for biofuel production due to its rapid growth rate and lignin-free characteristic. In this study, the lipid extracted microalgae biomass residues was used as the material to produce isoprene, α-pinene and β-pinene with the engineered E. coli strain. We adopted an optimal sulfuric acid hydrolysis method to convert holocellulose into fermentable sugar efficiently (6.37 g/L) and explored a novel detoxification strategy (phosphoric acid/calcium hydroxide) to remove inhibitors notably. 55.32 % acetic acid, 99.19 % furfural and 98.22 % 5-HMF were cut down with the phosphoric acid/calcium hydroxide method, and the fermentation concentration of isoprene (223.23 mg/L), α-pinene (382.21 μg/L) and β-pinene (17.4 mg/L) using the detoxified hydrolysate as the carbon source account for approximately 86.02 %, 90.16 % and 88.32 % of those produced by the engineered E. coli strain fermented on pure glucose, respectively.

Coronary microvascular dysfunction (CMD) is a clinical entity linked with various risk factors that significantly affect cardiac morbidity and mortality. Hypertension, one of the most important, causes both functional and structural alterations in the microvasculature, promoting the occurrence and progression of microvascular angina. Endothelial dysfunction and capillary rarefaction play the most significant role in the development of CMD among patients with hypertension. CMD is also related to several hypertension-related morphological and functional changes in the myocardium in the subclinical and early clinical stages, including left ventricular hypertrophy, interstitial myocardial fibrosis, and diastolic dysfunction. This indicates the fact that CMD, especially if associated with hypertension, is a subclinical marker of end-organ damage and heart failure, particularly the one with preserved ejection fraction. This is why it is important to search for microvascular angina in every patient with hypertension and chest pain not associated with obstructive coronary artery disease. Several highly sensitive and specific non-invasive and invasive diagnostic modalities have been developed to evaluate the presence and severity of CMD, but also to investigate additional complications that can affect further prognosis, especially among those with hypertensive heart disease. Although various pharmacological and interventional treatments demonstrated certain clinical effects, integrated diagnostic and therapeutic algorithms are necessary to reduce the burden of this emerging condition.

The combined effects of the thermal processing (i.e., sterilisation treatment) and the prior frozen storage time (3 or 6 months at –18 ºC) on the quality loss in canned Atlantic horse mackerel (Trachurus trachurus) were determined. Thus, the sterilisation step led to a remarkable (p&lt;0.05) formation in canned fish muscle of fluorescent compounds, free fatty acids (FFAs) and trimethylamine and to an increase of the L* and b* colour parameters; meantime, a decrease (p&lt;0.05) of the total ω3 FA/total ω6 FA ratio and the a* colour value were detected. The prior frozen storage period led to an increased (p&lt;0.05) lipid oxidation (peroxide, thiobarbituric acid reactive substance and fluorescent compound formation) and hydrolysis (FFA formation) development and to increased L* and b* colour values in the corresponding canned samples; additionally, a lower (p&lt;0.05) polyene index and phospholipid content were observed in canned fish previously subjected to frozen storage. In most indices, physico-chemical changes related to quality loss were found higher if the previous storage period was increased. According to the marked effects of the sterilisation step and the prior frozen storage period, optimisation of such processing conditions is recommended to maximise the quality of canned horse mackerel.

Fibroblasts are differentiated to myofibroblasts and produce collagen and other extracellular matrix when the heart is exposed to stresses. Myocardial infarction and pressure overload-induced hypertrophy are major stresses to induce differentiation of fibroblasts. Since collagen can compensate the missing tissue due to injury, appropriate production of collagen is beneficial for the injured heart against rupture. However, excessive deposition of collagen is called fibrosis and causes cardiac dysfunction. After fibroblasts are differentiated to myofibroblasts, myofibroblasts can further change their phenotypes. In addition, myofibroblasts are found to have a new function other than collagen production. Myofibroblasts have macrophage-like functions that engulf dead cells and secrete anti-inflammatory cytokines. So far, research on fibroblasts has been delayed due to the lack of available markers for selective isolation of fibroblasts. In recent years, it has become possible to genetically label fibroblasts, sequence the cells at single cell levels, and manipulate function or the number of cells. Based on new technologies, the origin of fibroblasts and myofibroblasts, time-dependent changes of fibroblast states after injury, and heterogeneity have been demonstrated. Here, I will introduce recent advances in fibroblasts and myofibroblasts.

Since the outbreak of the COVID-19 pandemic, patients infected with COVID-19 may experience abnormal heart rates, posing potential health risks. This study proposes a non-contact method for measuring heart rate (HR) and heart rate variability (HRV) to effectively reduce the risk of infection and assist healthcare professionals in more accurate diagnosis and treatment. In this study, except for the different image acquisition method, other research processes and methods are similar to the research methods in [15]. The image acquisition method is changed from forehead image to palm image. The new non-contact measurement performance of the proposed method can effectively not only avoid infection concerns but also obtain heart rate and HRV quickly and conveniently, providing higher accuracy for physiological parameters, root mean square error (RMSE), and mean absolute percentage error (MAPE) compared to those in recently published papers.

Cirrhosis is a chronic disease with multiple etiologies, multiple manifestations, and multi-organ involvement. Affects about 200 million people worldwide. Its main complication is Portal hypertension (PHT). Cirrhotic cardiomyopathy is a consequence of PHT, with heart failure (HF) being the main manifestation. On the other hand, for people with cardiopathy due to other reasons beyond cirrhosis, the presence of the last could act as a trigger to acute HF. Finally, when HF and cirrhosis coexist, the renal system suffers the most, originating from type-5 cardio-renal syndrome, a complex entity with many challenges in diagnosis and treatment. This entity was recently defined and there is a lack of data on the epidemiology of this syndrome. A 77-year-old woman, with cardiovascular risk factors; heart failure with reduced ejection fraction (HFrEF), secondary ischemic and valvular cardiopathy, chronic Kidney disease (CKD), and stable decompensated cirrhosis, went to the emergency department after progressive abdominal perimeter augmentation, legs’ edema and hematochezia. It was assumed acute decompensated cirrhosis and acute decompensated chronic kidney disease, had triggered digestive bleeding and the patient stayed hospitalized. Intravenous diuretic therapy was started but, the ascites and kidney function got worse, the Nt pro-BNP grew until 1125000 pg/ml, and a transthoracic echocardiography showed important signs of congestion, isolated right ventricular dysfunction, with normal cardiac output. After teamwork’s discussion, a type-5 cardio-renal syndrome was assumed deciding not to act on tricuspid regurgitation due to the maladaptive RV remodeling. Hepatorenal syndrome treatment was begun (oral terlipressin and intravenous albumin), followed by decongestion therapy, resulting in a marked improvement in clinical presentation. The kidney, heart, and liver recovered to these basal states. With this clinical case, the authors want to show how multidisciplinary management is important to face tricuspid regurgitation and right ventricular dysfunction.

Background: Galectin-3 (Gal-3) overexpression is associated with fibroblastic proliferation and the production of collagen, resulting in increased cardiac fibrosis and remodelling. Aim of the study was to investigate on the expression of Gal-3 in hypertrophic hearts. We examined 19 surgical specimens taken from interventricular septum of 8 patients with Tetralogy of Fallot, 4 patients with aortic valve stenosis, 1 cardiac explant affected from dilated cardiomyopathy, and 6 myocardial biopsies of patients submitted to heart transplantation. Methods: All the samples were routinely processed, stained with Hematoxylin-Eosin, Trichromic stain and elastic fiber stain and selected by having the morphological features of myocardial hy-pertrophy: myocytolysis, nuclear pleomorphism, interstitial fibrosis. Results: At immunohistochemistry, myocardial fibers showed cytoplasmic expression of Gal-3 in the 4 patients with aortic valve stenosis (diffuse in 3 and mild in 1), in the 1 patient with cardiac explant (mild) and in the 4/6 transplanted hearts (mild and focal in 3 and diffuse in 1). The 8 patients affected from Tetralogy of Fallot and 2 patients with transplanted hearts resulted negative. Conclusions: The results agreed with the hypothesis that Gal-3 may play a role in cardiac hyper-trophy; its expression in myocardial fibers is not related with the morphological aspects as suggested by the absence in pediatric cases. The presence in myocardial biopsies taken from transplanted hearts would suggest a possible role in predicting clinical outcome of such patients.

We have developed deep learning models for automatic identification of the maternal heart rate (MHR) and, more generally, false signals (FSs) on fetal heart rate (FHR) recordings. The models can be used to preprocess FHR data prior to automated analysis or as a clinical alert system to assist the practitioner. Three models were developed and used to detect (i) FSs on the MHR channel (the FSMHR model), (ii) the MHR and FSs on the Doppler FHR sensor (the FSDop model), and (iii) FSs on the scalp ECG channel (the FSScalp model). The FSDop model was the most useful because FSs are far more frequent on the Doppler FHR channel. All three models were based on a multilayer, symmetric, GRU and were trained on data recorded during the first and second stages of delivery. The FSMHR and FSDop models were also trained on antepartum recordings. The training dataset contained 1030 expert-annotated periods (mean duration: 36 min) from 635 recordings. In an initial evaluation of routine clinical practice, 30 fully annotated recordings for each sensor type (mean duration: 5 h for MHR and Doppler sensors, and 3 h for the scalp ECG sensor) were analyzed. The sensitivity, positive predictive value (PPV) and accuracy were respectively 62.20%, 87.1% and 99.90% for the FSMHR model, 93.1%, 95.6% and 99.68% for the FSDop model, and 44.6%, 87.2% and 99.93% for the FSScalp model. We built a second test dataset with a more solid ground truth by selecting 45 periods (lasting 20 min, on average) on which the Doppler FHR and scalp ECG signals were recorded simultaneously. Using scalp ECG data, the experts estimated the true FHR value more reliably and thus annotated the Doppler FHR channel more precisely. The models achieved a sensitivity of 53.3%, a PPV of 62.4%, and an accuracy of 97.29%. In comparison, two experts (blinded to the scalp ECG data) respectively achieved a sensitivity of 15.7%, a PPV of 74.3%, and an accuracy of 96.91% and a sensitivity of 60.7%, a PPV of 83.5% and an accuracy of 98.24%. Hence, the models performed at expert level (better than one expert and worse than the other), although a well-trained expert with good knowledge of FSs could probably do better in some cases. The models and datasets have been included in the Fetal Heart Rate Morphological Analysis open-source MATLAB toolbox and can be used freely for research purposes.

In the context of type 2 diabetes (T2DM), fasting and postprandial hyperglucagonemia have long been linked to the disease's development and progression. However, recent studies have brought to light the positive impact of glucagon-agonists on lipid metabolism and energy homeostasis. This review delves into the intricate relationship and underlying mechanisms between glucagon and nutrient composition, which may hold promise in devising novel therapeutic approaches for T2DM management.

In the recent days, lipid nanoparticles have been successfully emerged as one of the most advanced technology for highly efficient in vivo delivery of exogenous mRNA, especially for delivery of COVID-19 vaccines. For the vaccines to be successful or protective, they require highly efficient mRNA delivery systems. However, developing effective, translatable vaccines with better safety against some of the SARS‐CoV‐2 variants is still a challenge. Lipid nanoparticles (LNPs) are composed of four different types of lipids including ionizable lipids, helper or neutral lipids, cholesterol and polyethylene glycol (PEG) attached lipids. In this review, we present recent advancements and insights in designing the advanced LNPs and their composition and properties, with a subsequent discussion on the development of COVID-19 vaccines. In particular, as the ionizable lipids are most important drivers for complexing the mRNA and in vivo delivery, the role of ionizable lipids in mRNA vaccines discussed in detail. Furthermore, the use of LNPs as effective delivery vehicles for vaccination, genome editing, and protein replacement therapy were discussed. Finally, expert opinion of LNPs for mRNA vaccines were discussed which might address the future challenges in the development of mRNA vaccines employing highly efficient LNPs using novel set of ionizable lipids.

This review provides informations and details for the fabrication of biosensors that are composed from lipid membranes and have been utilized and applied to rapidly detect food toxic compounds, environmental pollutants and analytes of clinical interest. Biosensors based on polymeric lipid membranes have been used to rapidly detect a wide range of these analytes and offer several advantages such as fast response, high sensitivity and selectivity, can be portable for in the field applications, and small size. A description of the construction of these devices and their applications for the rapid detection of food toxic substance, environmental pollutants and analytes of clinical interest is provided in this review.

Intracellular lipid droplets (LDs) can occur in response to inflammation, metabolic stresses, and other physiological/pathological processes. Herein, we investigated whether spike proteins of SARS-CoV-2 induce LDs in human peripheral blood mononuclear cells (PBMCs) and in pulmonary microvascular endothelial cells (HPMEC). PBMCs or HPMEC were incubated alone or with endotoxin-free recombinant variants of trimeric spike glycoproteins (Alpha, Beta, Delta, and Omicron, 12 µg/ml). Afterwards, cells were stained with Oil Red O for LDs, cytokine release was determined by ELISA, and the gene expression was analyzed by real-time PCR using TaqMan assays. Our data show that spikes induce LDs in PBMCs but not in HPMEC. In line, in PBMCs spike proteins lower expression of genes involving lipid metabolism and LDs formation, such as SREBF1, HMGCS1, LDLR, and CD36. On the other hand, PBMCs exposed to spikes for 6 or 18 h did not increase in IL-1β, IL-6, IL-8, MCP-1, and TNFα release or expression as compared to non-treated controls. Thus, spike-induced LDs formation in PBMCs seems to be not related to cell inflammatory activation. Further detailed studies are warranted to investigate in which specific immune cells spikes induce LDs, and what are pathophysiological mechanisms and consequences of this induction in vivo.

Objectives: Evaluate hand-held echocardiography (HHE) performed and interpreted by trained Advanced Practice Providers (APPs) on hospitalized CHF patients for image quality and interpretation, by comparing against expert echocardiographer and SE findings. Background: Congestive heart failure (CHF) is associated with increased hospital admissions and mortality. While standard echocardiogram (SE) is the gold standard for cardiac assessment, it is not readily available. Hospitalized CHF patients require rapid assessment for expedited treatment. Methods: Over 6 months, five trained APPs performed HHE on hospitalized CHF patients and interpreted: a) Left ventricular (LV) size, b) LV ejection fraction (LVEF), and c) right atrial pressure (RAP). The study echocardiographer reviewed and blindly interpreted HHE images and compared with APPs and SE findings. Kappa-statistics determined the degree of agreement between APPs and study echocardiographer interpretation of HHE images and SE. Results: 80 CHF patients [age 73±14 years, 58% males; LVEF (by SE) 45±19%; 36.3% body mass indexes ≥30 kg/m2] were enrolled. HHE interpretation by APPs had good agreement for LVEF (kappa 0.79) with study echocardiographer and SE (kappa 0.74), and good agreement for RAP (kappa 0.67) with study echocardiographer. Correlation between absolute LVEF interpretation by study echocardiographer on HHE and SE was r=0.88 (p<0.0001). Conclusions: Trained APPs obtained diagnostic-quality HHE images and interpreted LV function and RAP in CHF patients, with good agreement with the study echocardiographer. LVEF by HHE correlated with LVEF by SE. Our study suggests trained APPs can use HHE to evaluate LVEF and RAP in CHF patients leading to expedited and optimized treatment.

Objective: Lipids are secreted into milk as bilayer-coated structures: milk lipid globules (MLGs). Adipophilin (ADRP) and perilipin 3 (TIP47) are associated with MLGs in human breast milk; however, the role of these proteins in milk lipid secretion is not fully understood. The aim of the study was to investigate levels of ADRP, TIP47 and total lipid content in human breast milk, their mutual correlations and dynamics during lactation. Research Methods & Procedures: Milk samples from 22 healthy lactating women (Caucasian, Central European) were collected at five time points during lactation (1–3, 12–14, 29–30, 88–90 and 178–180 days postpartum). Mass spectrometry-based method was used for quantification of ADRP and TIP47 in the samples. The gravimetric method was used to determine milk total lipid content. Results: We observed distinctive trends in ADRP, TIP47 levels and lipid content in human breast milk during the first 6 months of lactation. We also found a significant association between lipid content and ADRP, lipid content and TIP47, and ADRP and TIP47 concentrations in breast milk at all sampling points. Moreover, we derived an equation for estimating the mean lipid content of milk based on ADRP concentration in human breast milk. Conclusions: A mass spectrometry-based method was developed for quantifying ADRP and TIP47 in human breast milk. Strong mutual correlations were found between ADRP, TIP47 and total lipid content in human breast milk.

Neonatal electronic cardiac monitoring in labor and delivery room (DR-ECG) is shown to be sustained at a tertiary care regional perinatal center despite COVID-19 and other complex organizational challenges. In this contemporary cohort, initial increase in chest compressions at birth associated with the introduction of DR-ECG monitoring was mitigated by focused educational interventions on effective ventilation with no difference in neonatal mortality. DR-ECG may help our understanding of human and system factors, identify potential better practices for optimal resuscitation team performance and assess impact of targeted training initiatives on clinical outcomes.

Cardiac fibrosis is a severe outcome of Chagas disease (CD), caused by the protozoan Trypanosoma cruzi. Clinical evidence revealed a correlation between fibrosis levels with impaired cardiac performance in CD patients. Therefore, we sought to analyze the effect of inhibitors of TGF- (pirfenidone), p38-MAPK (losmapimod) and c-Jun (SP600125) on the modulation of collagen deposition in cardiac fibroblasts (CF) and in vivo models of T. cruzi chronic infection. Sirius Red/Fast green dye was used to quantify both collagen expression and total protein amount, assessing cytotoxicity. The compounds were also used to treat C57/Bl6 mice chronically infected with T. cruzi, Brazil strain. We identified an anti-fibrotic effect in vitro for pirfenidone (TGF-β inhibitor, IC50 114.3 μM), losmapimod (p38 inhibitor, IC50 17.6 μM) and SP600125 (c-Jun inhibitor, IC50 3.9 μM). This effect is independent of CF proliferation since these compounds do not affect T. cruzi-induced host cell multiplication as measured by BrdU incorporation. Assays of chronic infection of mice with T. cruzi have shown a reduction in heart collagen by pirfenidone. These results propose a novel approach to fibrosis therapy in CD, with the prospect of repurposing pirfenidone to prevent the onset of ECM accumulation in the heart of the patients.

Chamois are mountain ungulates (Subfamily Caprinae) which inhabit several medium and high altitude mountain ranges from southern Europe to the Near East. The first findings of Sarcocystis cysts in the musculature of chamois were reported in the 1970s. However, only limited work on the epidemiology of sarcocystosis and identification of the species of Sarcocystis in chamois has been done in the past. The present work was part of a comprehensive study on the parasites of chamois in Germany aiming to provide, for the first time, data on the prevalence and intensity of Sarcocystis infection in native Alpine chamois using histology examination of heart and/or diaphragm tissue samples collected from 216 chamois (40 kids and 176 chamois ranging of one up to 18 years of age). Sarcocysts were detected in either heart or diaphragm of 167/216 chamois (77.3%) with 131 of 183 heart samples and 127 of 215 diaphragm samples testing sarcocyst positive. Of the 181 chamois with both heart and diaphragm available (34 kids and animals up to 18 years of age), sarcocysts were detected in heart and/or diaphragm of 142 animals translating in an overall 78.5% prevalence of Sarcocystis infection (95%CI 72.5% - 84.4%). Sarcocysts were more frequently recorded in heart vs. diaphragm (72.4% vs. 56.4%; p=0.0021), and diaphragm positivity was associated with heart positivity (p=0.0001). Sarcocyst positivity (heart and/or diaphragm) was significantly (p<0.001) lower in kids than in the older chamois (27.1% vs. 88.6%, respectively) but prevalence did not differ between the sexes, regardless of the chamois’ age (p>0.3). Intensity of infection was generally low (<10 sarcocysts per cm² muscle cut) in both heart positive and diaphragm positive animals (94.7% and 93.7%, respectively) with heart yielding higher sarcocyst counts than diaphragm (p<0.001). Both heart and diaphragm sarcocyst counts were significantly (p<0.001) lower in kids than in the older chamois. Sarcocystis infection was demonstrated to be prevalent in chamois in Germany but intensity is apparently low. Further studies are desired to identify the species of Sarcocystis parasitizing the chamois using both phenotypic and molecular characteristics.

There is a bidirectional relationship between the heart and the gut. Gut microbiome is an excellent gut-homeostasis keeper since controls the growth of potentially harmful bacteria and protects the microbiota environment. There is evidence suggesting that diet rich in fatty acid can be metabolized and converted by gut microbiome and hepatic enzymes to trimethyl-amine N-oxide (TMAO) a product that is associated with atherogenesis, platelet dysfunction, thrombotic events, coronary artery disease, stroke, heart failure and ultimately death. Heart failure, by inducing gut ischemia and congestion and consequently gut barrier dysfunction promote an intestinal leak of microbes or even of their products, facilitating their entrance into the circulation and thus stimulating the low-grade inflammation and hence the immune response. Drugs used for heart failure may alter the gut microbiome, and conversely gut microbiome may modify the pharmacokinetic properties of the drugs. Modification of lifestyle based mainly on exercise and Mediterranean diet along with the use of pre- or probiotics may be beneficial to some extent for the gut microbiome environment. The potential role of gut microbiome in heart failure development and outcomes is a fruitful area of future research.

Background: Hypertrophic Cardiomyopathy (HCM) is the most common inherited Cardiomyopathy. The hallmark of HCM is myocardial fibrosis which contributes to heart failure, arrhythmias, and sudden cardiac death (SCD). Objective: To identify the factors implicated in heart failure symptoms and functional capacity of patients with HCM. Methods: In this cohort study, 43 patients with HCM were recruited. According to functional capacity and symptoms presentation, patients were categorized according to NYHA classification, and echocardiographic measurements of left ventricle systolic and diastolic function have been conducted. The echocardiographic assessment of right vetriculo-arterial coupling (RVAC) has been made by calculating the tricuspid annular peak systolic tissue Doppler velocity (TASV)/estimated RV systolic pressure (RVSP) ratio. Results: Almost half, 22 (51%) of our study population present symptoms of heart failure and were categorized as the symptomatic group - NYHA 2 or higher. Maximum LVOT gradient, RVSP, and the ratio of E/e’ were higher in the “symptomatic” compared to the “asymptomatic” group. TASV was lower in the “symptomatic” compared to the asymptomatic group (11±1cm/sex vs. 13±2cm/sec, p=0.04). However, there was no difference in other potentially influential factors, such as heart rate or systemic blood pressure. The SCD risk score does not differ between the two studied groups. The RVAC (estimated with the TASV/RVSP ratio) was lower in the “symptomatic” compared with the “asymptomatic” group (0.32±0.09 vs. 0.46±0.11, p<0.001). Conclusion: A low RVAC (as TASV/RVSP ratio) value could represent an echocardiographic marker of right ventricular-arterial uncoupling in patients with HCM and may impaired functional status.

Heart rate variability (HRV) is commonly intended as the variation in the heart rate (HR) and it is evaluated in the time and frequency domains with various well known methods. In the present paper, we first consider an abstract model in which the HR is the instantaneous frequency of an otherwise periodic signal such as the electrocardiogram (ECG). Thus the ECG is assumed as a frequency modulated signal, or carrier signal, where HRV or HRVt is a supposed time-domain signal which is frequency modulating the carrier ECG signal around its average frequency. Hence we describe an algorithm able to frequency demodulate the ECG signal to extract a continuous signal HRVt with possibly enough time resolution to analyse fast time-domain variations in the instantaneous HR. After exhaustive testing of the method on simulated frequency modulated sinusoidal signals, we have applied the procedure on actual ECG tracings. The purpose of the work is to eventually use the heart as a kind of biological sensor of the fast activity of the autonomic nervous system (ANS) to study the ANS ultra-short-term event-evoked responses. A few preliminary, not clinical, real examples are also given.

During the 90 days following hospitalization for acute heart failure, ejection fraction and type of discharge medications have been shown in clinical trials to have little effect on mortality. We examined the recent literature addressing brain-related etiologies of sudden death following heart failure. Two mechanisms of sudden unexpected death have been suggested to possibly result from 4 significant influences on pathophysiology in the brain. The two causes of death are severe cardiac arrhythmia, and neurogenic pulmonary edema. They are both mediated through the brainstem autonomic nuclei generally, and executed specifically through the dorsal motor nucleus of the vagus nerve. The four significant influences on pathophysiology in the brainstem autonomic nuclei are: 1) Hyper-stimulation of neurons in the solitary tract nucleus, increasing their metabolic requirements; 2) Inadequate blood flow at a vascular watershed terminus; 3) Additionally decreased blood flow following vasoconstriction related to relative hyperventilation and decreased pCO2 levels; 4) Gravitational ischemia in the brain—caused by the weight of the brain mass sitting above the brainstem. Changes in head tilt release gravitational ischemia in the brain. There is no specific head position (relative to gravity) that is considered favorable or unfavorable for an extended period of time (i.e. more than 24 hours). Even a small degree of head elevation, used in managing pulmonary congestion, may increase gravitational ischemia in the posterior fossa and brainstem. In this paper we suggest a new and important research avenue for intervening in cardiac arrhythmias, and preventing their occurrence, through the non-invasive use of head-tilting, and other head repositioning maneuvers. This could potentially help many geriatric patients with heart failure, who have decreased mobility in bed, and who tend to stay in one position longer, thereby increasing gravitational ischemia in the brain.

Heart failure with preserved ejection fraction (HFpEF) is a leading form of human cardiovascular disease and commonly associated with systemic hypertension. Unique evolved adaptations in giraffe myocardia may be a natural animal model of resistance to HFpEF. In humans, pressure-overload induced left ventricular thickening (PLVT) impairs diastolic relaxation, elevates left atrial pressures and may progress to heart failure with symptoms including exercise intolerance. In healthy giraffe, the left ventricle thickens as developmental neck lengthening widens the vertical distance between the heart and head increasing pressures needed to maintain constant brain perfusion. Yet, diastolic relaxation and exercise capacity are unimpaired, a critical adaptation for prey species such as giraffe. The proximate mechanisms underlying this unique cardiovascular physiology are not yet characterized. Developmental PLVT in giraffe emerges as a species-specific evolved adaptation which offers a roadmap for identifying innovations in therapeutic and prevention strategies for HFpEF.

Diabetes mellitus is associated with cardiovascular, ophthalmic, and renal comorbidities. Among these, diabetic cardiomyopathy (DCM) causes the most severe symptoms and is considered to be a major health problem worldwide. Exercise is widely known as an effective strategy for the prevention and treatment of many chronic diseases. Importantly, the onset of complications arising from diabetes can be delayed or even prevented by exercise. Regular exercise is reported to have positive effects on diabetes mellitus and the development of DCM. The protective effects of exercise include the prevention of cardiac apoptosis, fibrosis, oxidative stress, and microvascular diseases, as well as improvement in cardiac mitochondrial function, and calcium regulation. The present review summarizes the recent findings to describe the potential mechanisms by which exercise may prevent DCM and heart failure.

Bile acids (BA) are classically known as an agent important in lipid absorption and cholesterol metabolism. Nowadays, BAs have been found to be involved in various cellular signaling pathways such as protein kinase cascades, cyclic AMP (cAMP) synthesis and calcium mobilization. In addition, they have also been shown to regulate glucose and energy homeostasis. Bile acids are ligands for several nuclear hormone receptors, including FXR. Recently, muscarinic receptor and TGR5, G-protein-coupled receptor (GPCR), have been suggested to play a role in bile acid activity which is independent of nuclear hormone receptors. Moreover, BAs have also been studied in other GPCR associated pathways, namely sphingosine-1-posphate and glucagon receptor. Hydrophobic bile acids have been proven to affect heart rate and its contraction. Elevated bile acids are associated with arrhythmias in adults and fetal heart. Altered ratios of primary and secondary bile acid are reported in chronic heart failure patients. Meanwhile in patients with liver cirrhosis, cardiac dysfunction has been strongly linked to the increase of serum bile acid concentrations. In contrast, the most hydrophilic BA known as ursodeoxycholic acid has been found beneficial in improving peripheral blood flow in chronic heart failure patients and protecting heart against reperfusion injury.

Introduction In sacubitril-valsartan (sacub/v), the effects of an angiotensin II receptor blocker (ARB) exerted by valsartan are strengthened by the addition of sacubitril, an inhibitor of neutral endopeptidases. PARADIGM - HF study proved this association to be superior to enalapril in reducing both all-cause death and cardiovascular mortality, as well as heart failure (HF) hospitalizations in patients with cardiac insufficiency and reduced left ventricular ejection fraction( HFREF) belonging to NYHA class II-IV. To test whether even in our experience sacub/v is associated with favorable outcomes concerning mortality and morbidity, an outpatient small population of HFREF patients was retrospectively studied, of whom one third was treated with sacub/v instead of conventional therapy with ACE -inhibitors or ARBs. Methods A retrospective cohort study was carried out to assess the effects of sacub/v in addition to beta-blocker and mineral receptor antagonist (MRA) in a group of HFREF patients in NYHA classes II-III compared with conventional therapy (comprising ACE inhibitor or ARB added to beta-blocker plus a MRA) administered in a second group of HFREF patients with comparable clinical features retrospectively enrolled as controls. In the two groups, the therapeutic regimen was established in accordance with the preferences of the treating physician. Additionally, in both groups, evidence-based drug therapy was supplemented by the adjunct of a loop diuretic, usually furosemide, at variable doses. The primary outcomes of interest were all-cause death and HF hospitalizations. Safety outcomes were symptomatic hypotension, angioedema, hyperkalemia and worsening renal function. Results Mortality at six months was 6.8% in patients under therapy with sacub/v versus 34% in those treated with conventional therapy (odds ratio[OR] = 0.14; 95% CI: 0.04-0.49). Moreover, HF hospitalizations in the observation period considered were 4.5% in sacub/v group versus 59% in the conventional therapy group (OR = 0.03; 95% CI: 0.01–0.14). Safety outcomes included in our study (angioedema, hyperkalemia, hypotension and worsening renal function) showed a comparable profile in the two groups, with evidence of good tolerability of sacub/v , except for the side - effect " hypotension" (PAS < 100 mm Hg) , found in 15.9% of patients under sacub/v versus 5.7% reported in controls (OR = 3.14; 95% CI: 0.94–10.55). Conclusions In our experience, sacub/v has yielded a strong protection against both all-cause death and HF hospitalizations at six months , in the absence of significant noxious side effects. Nevertheless, considering the retrospective character of the study and the relatively exiguous sample size, further post marketing observational studies would be desirable . In particular, studies aiming at exploring safety of the new pharmacologic principle, namely mainly focusing on hypotension and angioedema, are warranted, in order to validate further this very efficacious molecule for therapy of chronic HF, especially stable HFREF in NYHA classes II-III.

Pregnancy at advanced maternal age (AMA) is a condition of potential risk for the development of maternal-fetal complications with possible repercussions even in the long-term. Here, we analyzed the changes of plasma redox balance and the effects of plasma on human umbilical cord mesenchymal cells (hUMSCs) in AMA pregnant women (patients) at various timing of pregnancy. One hundred patients and twenty pregnant women younger than 40 years (controls) were recruited, and evaluated at various timings during pregnancy until after delivery. Plasma samples were used to measure the thiobarbituric acid reactive substances (TBARS), glutathione and nitric oxide (NO). In addition, plasma was used to stimulate the hUMSCs, which were tested for cell viability, reactive oxygen species (ROS) and NO release. The obtained results showed that throughout pregnancy until after delivery in patients the levels of plasma glutathione and NO were lower than those of controls, while those of TBARS were higher. Moreover, plasma of patients reduced cell viability and NO release, and increased ROS release in hUMSCs. Our results highlighted alterations in the redox balance and the presence of potentially harmful circulating factors in plasma of patients They could have clinical relevance for the prevention of complications related to AMA pregnancy.

Sixteen crossbred rabbits (New Zealand white x Thai native breed) were randomly divided into two groups of eight to determine the effects of daily oral administration of crude extracts from the butterfly pea (Clitoria ternatea L.) from weaning (at 35 days) to slaughter (at 90 days). Effects on phagocytic activity of blood polymorphoneuclear leukocytes, serum biochemistry, meat quality, muscular lipid peroxidation, apparent digestibility, and gut histology were studied. The results revealed that the phagocytic function of circulating leukocytes (75 and 90 days) and alveolar macrophages (90 days) did not differ between the two groups. At slaughter, treated rabbits had lower blood urea nitrogen concentrations and higher liver weight than control rabbits (p &lt; 0.05). After chilling at 4°C for 24 hours, lower meat pH and alteration of meat color (a brighter, less yellow, Hue angle and color saturation) were observed in the treated group (p &lt; 0.05). Furthermore, lipid peroxidation (measured at 3, 5 and 7 storage days) in the meat of treated rabbits was lower than in controls (p &lt; 0.05). Apparent digestibility (analyzed at 46 days for four days) revealed improved organic matter and ether extracts in the treated group (p &lt; 0.05), whereas gut histology was unaffected. In conclusion, butterfly pea extract supplementation did not affect phagocytic function but led to a modification in meat color, delayed lipid peroxidation, and improved digestibility.

Inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis, is a disease of chronic inflammatory conditions of the intestinal tract due to disturbance of the inflammation and immune system. Symptoms of IBD include abdominal pain, diarrhea, bleeding, reduced weight, and fatigue. In IBD, the immune system attacks the intestinal tract's inner wall, causing chronic inflammation and tissue damage. In particular, IL-6 and IL-17 act on immune cells, including T cells and macrophages, to amplify the immune responses so that tissue damage and morphological changes occur. Of note, excessive calorie intake and obesity also affect the immune system due to inflammation caused by lipotoxicity and changes in lipids supply. Similarly, individuals with IBD have alterations in liver function after sustained high-fat diet feeding. In addition, excess dietary fat intake, along with alterations in primary and secondary bile acids in the colon, can affect the onset and progression of IBD because inflammatory cytokines contribute to insulin resistance; the factors include the release of inflammatory cytokines, oxidative stress, and changes in intestinal microflora, which may also contribute to the disease progression. However, interfering with de novo fatty acid synthase by deleting the enzyme acetyl-CoA-carboxylase 1 in intestinal epithelial cells leads to the deficiency of epithelial crypt structures and tissue regeneration, which seems to be due to Lgr5+ intestinal stem cell function. Thus, conflicting reports exist regarding high-fat diet effects on IBD animal models. This review will focus on the pathological basis of the link between dietary lipids intake and IBD and cover currently available pharmacological approaches.

The circadian clock is a 24-hour cycle within the body that regulates various factors, including sleep, body temperature, and hormone secretion. It allows the body to adjust to the light and dark cycle. Disruptions to the circadian rhythm are important risk factors for many diseases, including neurodegenerative illnesses. The central clock is controlled by the clock genes in the suprachiasmatic nucleus (SCN) of the brain, and one of the main functions of the circadian clock is to regulate lipid metabolism. There has been a lack of investigation on the circadian regulation of lipid metabolism-related apolipoprotein genes in the brain; thus, this study sought to summarize the rhythmic expression of clock genes and lipid metabolism-related apolipoprotein genes within the SCN of Mus musculus. Out of the 20 apolipoprotein genes that were studied by the published database, all 9 genes were highly expressed in the SCN. Most of the 6 genes showed rhythmic expression in the brain of mice, suggesting that the master clock might regulate them. The results, therefore, reveal a potential target for preventing and treating circadian disorders. We summarized most studies of lipid-related apolipoprotein genes within limited locations of the SCN and brain to further understand how disordered cerebral lipid metabolism causes multiple brain diseases and disorders. We reviewed recent studies, determined the unexplored questions, and identified a potential direction for further research.

Pancreatic cancer has a poor prognosis with its five-year survival rate lower than that of any other cancer type because it is difficult to detect in the early stages. Gemcitabine, a standard treatment for pancreatic cancer, often has poor outcomes for patients as a result of chemoresistance. Therefore, novel therapeutic targets must be identified to overcome gemcitabine-resistance. Here, we found that SLC38A5, a glutamine transporter, is more highly overexpressed in gemcitabine-resistant patients than in gemcitabine-sensitive patients. Furthermore, the deletion of SLC38A5 decreased the proliferation and migration of gemcitabine-resistant PDAC cells. We also found that the inhibition of SLC38A5 triggered the ferroptosis signaling pathway via RNA sequencing. Also, silencing SLC38A5 induced mitochondrial dysfunction and reduced glutamine uptake and glutathione (GSH) levels, and downregulated the expressions of GSH-related genes NRF2 and GPX4. The blockade of glutamine uptake negatively modulated the mTOR-SREBP1-SCD1 signaling pathway. Therefore, suppression of SLC38A5 triggers ferroptosis via two pathways that regulate lipid ROS levels. Similarly, we observed knockdown of SLC38A5 restored gemcitabine sensitivity by hindering tumor growth and metastasis in the orthotopic mouse model. Altogether, our results demonstrated that SLC38A5 could be a novel therapeutic target to overcome gemcitabine-resistance in PDAC therapy.

Galanthus elwesii Hook is an important plant species of the Amaryllidaceae family and is used for medicinal purposes with its valuable bioactive compounds. The present study was conducted to investigate the effects of foliar salicylic acid (SA) and zinc (Zn) treatments on proline, carotenoid, chlorophyll content and anti-oxidant enzyme activity in G. elwesii. The ascorbate peroxidase (APX), catalase (CAT) enzyme activity, and protein contents were determined with ascorbate oxidation, hydrogen peroxide (H2O2), and Bradford experiments, respectively. The plants were treated with three different concentrations of SA (0.5, 1, and 2 mM) and, and Zn (40, 80, and 120 mM) were compared with the control. Fresh leaves were harvested in the study. APX (3.99 ± 0.58 EU/mg protein) and CAT (154.64 ± 4.10 EU/mg protein) were obtained from Zn 80 and 120 mM treatments at the highest level, respectively. Proline, chlorophyll b, and carotenoid content increased 12.4, 1.54 and 3.95-fold, respectively, in 0.5 mM SA treatments when matched with control group. It was found that increasing doses of SA and Zn increased the content of malondialdehyde (MDA), but this was not at a significant level. The total chlorophyll content increased 2.27-fold in Zn 120 mM + SA 2 mM treatment and the chlorophyll content increased 2.41-fold in Zn 40 mM + SA 1 mM treatment.

Lipid nanoparticles (LNPs) are promising carriers for constructing drug delivery systems (DDSs) in disease treatments. Previous studies have suggested that lipid composition and biophysical properties of LNPs can significantly impact their interaction with cells and tissues, allowing for the development of suitable LNPs for precise drug delivery. Our previous study proposed the concept and facile preparation of reconstituted lipid nanoparticles (rLNPs), which not only have the advantages of traditional LNPs but also contain the lipids of mother cell/tissue. In this study, we have found that brain-derived rLNPs (B-rLNPs) can have much better accumulation to the ischemic area of the ischemic stroke (IS) model than liver-derived rLNPs (L-rLNPs). This homing effect hopefully makes rLNPs a useful tool for developing highly accessible devices with homologous targeting ability for precise drug delivery.

Antimicrobial peptides (AMPs) are generally membrane-active compounds that physically disrupt bacterial membranes. Despite extensive research, the precise mode of action of AMPs is still a topic of great debate. This work demonstrates that the initial interaction between the Gram-negative E. coli and AMPs is driven by lipopolysaccharides (LPS) that act as kinetic barriers for the binding of AMPs to the bacterial membrane. A combination of SPR and NMR experiments provide evidence suggesting that cationic AMPs first bind to the negatively charged LPS before reaching a binding place in the lipid bilayer. In the event that the initial LPS-binding is too strong (corresponding to a low dissociation rate), the cationic AMPs cannot effectively get from the LPS to the membrane and their antimicrobial potency will thus be diminished. On the other hand, the AMPs must also be able to effectively interact with the membrane to exert its activity. The ability of the studied cyclic hexapeptides to bind LPS and to translocate into a lipid membrane is related to the nature of the cationic charge (arginine vs lysine) and to the distribution of hydrophobicity along the molecule (alternating vs clumped tryptophan).

Introduction Currently, the increase in the percentage of obese people observed along with the development of civilization, reaching the level of a global pandemic, has forced the search for methods of effective and permanent obesity treatment. Obesity is a multifactorial disease, it coexists with many disease entities and requires multidisciplinary treatment. Obesity leads to metabolic changes in the form of metabolic syndrome, which includes, among others, atherogenic dyslipidemia. The proven relationship between dyslipidemia and cardiovascular risk enforces the need to effectively improve the lipid profile of obese patients. Laparoscopic sleeve gastrectomy is a method of surgical treatment of morbid obesity which improves bariatric and metabolic parameters. The aim of the study was to assess the effectiveness of laparoscopic sleeve gastrectomy (LSG) in improving lipid profile parameters in 1-year follow-up. Material and Methods Bariatric parameters of 196 patients who underwent laparoscopic sleeve gastrectomy as well as lipid profile of total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-NDL, and triglycerides (TG) in 1-year observation were analyzed. Results Improvements in bariatric parameters were observed in patients after LSG. Total cholesterol, low-density lipoprotein (LDL), triglycerides and non-HDL levels decrease were observed along with the increase of high-density lipoprotein (HDL) cholesterol level. Conclusions Sleeve gastrectomy is an effective method of treating obesity and improving the lipid profile in obese patients.

Adipocytes play a critical role in maintaining a healthy systemic metabolism by storing and releasing energy in the form of fat and helping to regulate glucose and lipid levels in the body. Adipogenesis is the process through which pre-adipocytes are differentiated into mature adipocytes. It is a complex process involving various transcription factors and signaling pathways. Dysregulation of adipogenesis has been implicated in the development of obesity and metabolic disorders. Therefore, understanding the mechanisms that regulate adipogenesis and the factors that contribute to its dysregulation may provide insights into the prevention and treatment of these conditions. RNA Binding Motif Single Stranded Interacting Protein 1 (RBMS1) is a protein that binds to RNA and plays a critical role in various cellular processes such as alternative splicing, mRNA stability, and translation. The RBMS1 polymorphism has been shown to be associated with obesity and Type 2 diabetes, but the role of RBMS1 in adipose metabolism and adipogenesis is not known. We show that RBMS1 is highly expressed during the early phase of differentiation of the murine adipocyte cell line 3T3-L1 and is significantly upregulated in adipose tissue depots and adipocytes of high-fat-fed mice, implying a possible role in adipogenesis and adipose metabolism. Knockdown of RBMS1 in pre-adipocytes impacted the differentiation process and reduced the expression of some of the key adipogenic markers. Transcriptomic and proteomic analysis indicated that RBMS1 depletion affected the expression of several genes involved in major metabolic processes, including carbohydrate and lipid metabolism. Our findings imply that RBMS1 plays an important role in adipocyte metabolism and may offer novel therapeutic opportunity for metabolic disorders such as obesity and type 2 diabetes.

The misuse of antibiotics during the last decades led to the emergence of multidrug resistant pathogenic bacteria. This phenomenon constitutes a major public health issue. Consequently, the discovery of new antibacterials in the short term is crucial. Colicins, due to their antibacterial properties, thus constitute good candidates. These toxin proteins, produced by E. coli to kill enteric relative competitors, exhibit cytotoxicity through ionophoric activity or essential macromolecule degradation. Among the 25-colicin types known to date, colicin M (ColM) is the only one colicin interfering with peptidoglycan biosynthesis. Accordingly, ColM develops its lethal activity in E. coli periplasm by hydrolyzing the last peptidoglycan precursor, lipid II, into two dead-end products, thereby leading to cell lysis. Since the discovery of its unusual mode of action, several ColM orthologs have also been identified based on sequence alignments; all of the characterized ColM-like proteins display the same enzymatic activity of lipid II degradation and narrow antibacterial spectra. This publication aims at being an exhaustive review about what is currently known on this new family of antibacterial enzymes as well as on their potential use of food preservatives or therapeutic agents.

Background and Aims: Dyslipidemia and cardiovascular diseases (CAD) are comorbidities of nonalcoholic fatty liver disease (NAFLD), which ranges from steatosis to hepatocellular carcinoma (HCC). The rs599839 A>G variant, in the CELSR2-PSRC1-SORT1 cluster, has been associated CAD, but its impact on metabolic traits and liver damage in NAFLD has not been investigated yet. Methods: We evaluated the effect of the rs599839 variant in 1426 NAFLD patients (Overall cohort) of whom 131 have HCC (NAFLD-HCC), in 500,000 individuals from the UK Biobank Cohort (UKBBC) and in 366 HCC samples from The Cancer Genome Atlas (TCGA). Hepatic PSRC1, SORT1 and CELSR2 expressions were evaluated by RNAseq (n=125). Results: The rs599839 variant was associated with reduced circulating LDL, carotid intima-media thickness, carotid plaques and hypertension (p<0.05) in NAFLD patients and with protection against dyslipidemia in UKBBC. The G allele was associated with higher risk of HCC and advanced tumor stage (p<0.05) in the Overall cohort. Hepatic PSRC1, SORT1 and CELSR2 expressions were increased in NAFLD patients carrying the rs599839 variant (p<0.0001). SORT1 mRNA levels negatively correlated with circulating lipids and with those of genes involved in lipoprotein turnover (p<0.0001). Conversely, PSRC1 expression was positively related to that of genes implicated in cell proliferation (p<0.0001). In TCGA, PSRC1 over-expression promoted more aggressive HCC development (p<0.05). Conclusions: In sum, the rs599839 A>G variant improves dyslipidemia thus protecting against CAD in NAFLD patients, but as one it might promote HCC development by modulating SORT1 and PSRC1 expressions which impact on lipid metabolism and cell proliferation, respectively

Imperatorin is a chemical compound belong to Linear furan coumarins. Imperatorin is attracting considerable attention because of its anti-tumor, antibacterial, anti-inflammatory, anticoagulant and inhibition of myocardial hypetrophy and other pharmacological efficacy. However, imperatorin has limited water solubility and preferable lipid solubility, we decided to design and synthesize imperatorin lipid microsphere, to optimize preparation conditions. The aim was to develop and formulate imperatorin lipid microsphere through nano emulsion technology and apply the response surface-central composite design to optimize the imperatorin lipid microsphere formulation. Influence of content of amount of egg lecithin(A), amount of poloxamer188(B), soybean oil for injection accounted for the total percentage of oil phase(C) were investigated. Integrated effect of dependent variables including particle size(Y₁), polydispersity index(Y₂), Zeta potentials(Y₃), drug loading(Y₄), encapsulation efficiency(Y₅). Data of overall desirabiities were fitted to a second-order polynomial equation, through which three dimensional response surface graphs were described. Optimum experimental conditions were calculated by Design-Expert 8.06. Results indicated that the optimum preparation conditions were as follows: egg lecithin amount 1.39 g, poloxamer188 amount 0.21 g, soybean oil for injection amount 10.57%. Preparation of imperatorin lipid microsphere according to the optimum experimental conditions resulted in an overall desirability of 0.7286, while the particele size (168±0.54) nm, polydispersity index (PDI) (0.138±0.02), Zeta potentials (−43.5±0.5) mV, drug loading (0.833±0.27) mg·mL⁻¹, encapsulation efficiency (90±1.27)%. The difference between observed and predicted values of the overall desirability of the optimum formulation was in range from 2.4% to 4.3%. Subsequently, using the Scanning electron microscopy to observe the micromorphology of imperatorin lipid microsphere, the result shows that round globular of relatively uniform and sizes within 200nm.The proliferation study of imperatorin lipid microsphere on MDA-MB-231 was investigated by MTT method. Furthermore, pharmacokinetics in Sprague Dawley rats were evaluated using orbital bleeding. A sensitive and reliable liquid chromatography with High Performance Liquid Chromatography (HPLC) method was established and validated for the quantification of imperatorin in rat plasma samples. The data were calculated by DAS (Drug and statistics) pharmacokinetic software version3.2.6 (China). Results demonstrated that imperatorin lipid microsphere can significantly enhance the bioavailability of imperatorin and can significantly inhibit MDA-MB-231 cell proliferating. In conclusion, our results suggersted that the response surface-central composite design is suitable for the optimized lipid microspere formulation. Imperatorin Lipid microsphere can improve the bioavailability of imperatorin and inhibit the proliferation of MDA-MB-231 than that of imperatorin.

Diabetes mellitus (DM) has been defined as a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, insulin action, or both. This study includes (84) subjects, their age ranged from (40 to 54) years. (20) subjects were healthy chosen as control group and (64) patients with type 2 diabetes mellitus were divided into three groups according to their type of anti diabetic therapy: (23) newly diagnosed group without therapy (Group1), (20) with metformin therapy (Group2) and (21) with metformin plus glibenclamide therapies (Group3). In the study lipid profile level were quantitatively determine by enzymatic methods, in addition to that fasting plasma glucose (FPG), Glycated hemoglobin (HbA1c%) and body mass index (BMI) were identified in the patients. There is significant increase in the level of lipid profile in patients group. Metformin alone produce a non-significant favorable effect on all lipids profile parameters while metformin plus glibenclamide showed a significant reduction in TC and LDL-C.

Silymarin, a mixture of flavonolignan and flavonoid polyphenolic compounds extractable from the milk thistle seed, Silybum marianum, has anti-oxidant, anti-inflammatory, anti-cancer and anti-viral activities potentially useful in the treatment of several liver disorders, such as chronic liver diseases, cirrhosis and hepatocellular carcinoma. Equally promising are the effects of silymarin in protecting the brain from the inflammatory and oxidative stress effects by which metabolic syndrome contributes to neurodegenerative diseases. However, despite clinical trials have proved that silymarin is safe at high doses (>1500 mg/day) in humans, it suffers limiting factors such as low solubility in water (<50 μg/mL), low bioavailability and poor intestinal absorption. To improve its bioavailability and provide a prolonged silymarin release at the site of absorption, the use of nanotechnological strategies appears to be a promising method to potentiate the therapeutic action and promote sustained release of the active herbal extract. The purpose of this study is to review the different nanostructured systems available in literature as delivery strategies to improve the absorption and bioavailability of silymarin.

A 36-year-old professional marathon runner reported sudden heart palpitations occurring during competitions, with heart rates (HR) of 230 bpm recorded on sports HR monitor (HRM) over 4 years. These episodes subsided upon the cessation of exercise. Electrocardiograms, echocardiography, and cardiac magnetic resonance imaging results were borderline for athlete's heart. Because an electrophysiology study and standard exercise tests provoked no arrhythmia, doctors suspected Munchhausen syndrome. Ultimately, an exercise test that simulated the physical effort during a competition provoked tachyarrhythmia consistent with the HRM readings. This case demonstrates the diagnostic difficulties related to exercise-induced arrhythmia and the diagnostic usefulness of sports HRMs.

Hypoplastic left heart syndrome (HLHS) is a severe congenital heart disease (CHD) affecting 1 in 5,000 newborns. We constructed the interactome of 74 HLHS-associated genes identified from a large-scale mouse mutagenesis screen, augmenting it with 408 novel protein-protein interactions (PPIs) using our High-precision Protein-Protein Interaction Prediction (HiPPIP) model. The interactome is available on a webserver with advanced search capabilities (http://severus.dbmi.pitt.edu/wiki-HLHS). 364 genes including 73 novel interactors were differentially regulated in tissues/iPSC-derived cardiomyocytes of HLHS patients. Novel PPIs facilitated the identification of TOR signaling and endoplasmic reticulum stress modules. 60.5% of the interactome consisted of housekeeping genes that may harbor large-effect mutations and drive HLHS etiology but show limited transmission. Network proximity of diabetes, Alzheimer’s disease, and liver carcinoma-associated genes to HLHS genes suggested a mechanistic basis for their comorbidity with HLHS. Interactome genes showed tissue-specificity for sites of extracardiac anomalies (placenta, liver and brain). The HLHS interactome shared significant overlaps with the interactomes of ciliopathy and microcephaly-associated genes, with the shared genes respectively enriched for genes involved in intellectual disability and/or developmental delay, and neuronal death pathways. This supported the increased burden of ciliopathy variants and prevalence of neurological abnormalities observed among HLHS patients with developmental delay and microcephaly respectively.

Lipid droplet (LD) accumulation in hepatocytes is one of the major symptoms associated with fatty liver disease. Mitochondria play a key role in catabolizing fatty acids for energy production through β-oxidation. The interplay between mitochondria and LD assumes a crucial role in lipid metabolism, while it is obscure how mitochondrial morphology affects systemic lipid metabolism in the liver. We previously reported that cilnidipine, an already existing anti-hypertensive drug, has potency to prevent pathological mitochondrial fission by inhibiting protein-protein interaction between dynamin-related protein 1 (Drp1) and filamin, an actin-binding protein. Here, we found that cilnidipine and its new dihydropyridine (DHP) derivative, 1,4-DHP, which lacks Ca2+ channel blocking action of cilnidipine, prevent the palmitic ac-id-induced Drp1-filamin interaction, LD accumulation and cytotoxicity of human hepatic HepG2 cells. Cilnidipine and 1,4-DHP also suppressed the LD accumulation accompanied by reducing mitochondrial contact with LD in obese model and high fat diet-fed mouse livers. These results propose that targeting Drp1-filimin interaction becomes a new strategy for the prevention or treatment of fatty liver disease.

The utilization of natural waxes to form oleogels has emerged as a new and efficient technique for structuring liquid edible oil into solid-like structures for diverse food applications. The objective of this study was to investigate the interaction between sunflower wax (SW) and monoglycerides (MGs) in olive oil oleogels and to assess their physical characteristics and storage stability. To achieve this, pure SW and a combination of SW with MGs in a 1:1 ratio were examined within a total concentration range of 6-12% w/w. The formed oleogels were characterized based on their microstructure, melting and crystallization properties, textural characteristics, and oxidative stability during storage. All the oleogels were shelf-stable, and as the concentration increased, the hardness of the oleogels also increased. The crystals of SW oleogels were long needle-like, while the combination of SW and MGs led to the formation of crystal aggregates and rosette-like crystals. The differential scanning calorimetry and FTIR showed that the addition of MGs led to different crystal structures. The oxidation results revealed that oleogels had low peroxide and TBARS values throughout the 28-day storage. These results provide useful insights about the utilization of SW and MGs oleogels for potential applications in the food industry.

Sterol homeostasis in mammalian cells and tissues involves balancing three fundamental processes: de novo sterol biosynthesis; sterol import (e.g., from blood-borne lipoproteins); and sterol export. In complex tissues, composed of multiple different cell types (such as the retina), import and export also may involve intra-tissue, inter-cellular sterol exchange. Disruption of any of these processes can result in pathologies that impact the normal structure and function of the retina. Here, we provide a brief overview of what is known currently about sterol homeostasis in the vertebrate retina and offer a proposed path for future experimental work to further our understanding of these processes, with relevance to the development of novel therapeutic interventions for human diseases involving defective sterol homeostasis.

Hyperlipidemia (HLP) is a metabolic disease caused by abnormal lipid metabolism. Recently, the prevalence of HLP caused by poor dietary habits in the population has been increasing yearly. In addition, the current clinical use of lipid-lowering drugs has significant ameliorating effects on lipid levels but these actions are accompanied by certain side effects. However, bioactive marine substances have been verified to have various physiological activities such as hypoglycemic, antioxidant, antithrombotic, and effects on blood pressure. Therefore, marine biological sources of hypolipidemic active substances have attracted much attention. Moreover, some of the identified active substances have been found to induce hypolipidemia by inhibiting cholesterol synthesis and absorption, or by improving the composition of intestinal microorganisms. This article introduces the sources and classification of marine-derived hypolipidemic active substances, and describes current progress in research on the main mechanism of the hypolipidemic activity of these substances.

Ferroptosis is a recent form of non-apoptotic cell death, which occurs due to imbalance of iron homeostasis (iron overload). Oxidative stress due to the impairment of the antioxidant system is a major pathophysiology during ferroptosis, which eventually results in lipid peroxidation. The cellular and physiological biomarker of ferroptotic cell death includes major alteration in the glutathione peroxidase 4 (GPX4) antioxidant system and lipid peroxidation induced loss of plasma membrane integrity. This review elaborates the mechanism of oxidative stress which triggers ferroptosis.

In recent years, the field of drug delivery has seen a significant shift towards the exploration and utilisation of nanoparticles (NPs) as versatile carriers for therapeutic agents. With its ability to provide exact control over NPs' characteristics, microfluidics has emerged as a potent platform for the efficient and controlled synthesis of NPs. Microfluidic devices designed for precise fluid ma-nipulation at the micro-scale offer a unique platform for tailoring NP properties, enabling en-hanced control over NP properties such as size, morphology and size distribution while ensuring high batch-to-batch reproducibility. Microfluidics can be used to produce liposomes, solid lipid nanoparticles, polymer-based NPs and lipid-polymer hybrid NPs, as well as a variety of inorganic NPs such as silica, metal, metal oxide, quantum dots and carbon-based NPs, offering precise control over composition and surface properties. Its unique precision in tailoring NP properties holds great promise for advancing NP-based drug delivery systems in both clinical and industrial set-tings. Although challenges with large-scale production still remain, microfluidics offers a trans-formative approach to NP synthesis. In this review, starting from the historical development of microfluidic systems, the materials used to create the systems, microfabrication methods and system components will be discussed in order to provide the reader with an overview of micro-fluidic systems. In the following, studies on the fabrication of nanoparticles such as lipid NPs, polymeric NPs and inorganic NPs in microfluidic devices are included.

The production of oil by thraustochytrids is still costly because of its necessary and expensive culture medium. We evaluated the growth, lipid production, and fatty acid composition in an inexpensive, molasses-based (M) medium. Newly isolated thraustochytrid strains were identified as members of genus Aurantiochytrium based on 18S rRNA gene sequences. Isolated strains were repeatedly cultured in M medium for acclimatization to the medium. Acclimatized and non-acclimatized strains were cultured in basal GY medium and M medium. The lipid in the cultured cells were extracted by the Folch method, and the fatty acid composition was analyzed by gas chromatograph. The growth and lipid production in the non-acclimatized strains were significantly inhibited by culturing in M medium, whereas the growth and lipid production were improved by acclimatization treatment in the same medium. The fatty acid composition in the cultured cells were affected by the M medium compared to the basal GY medium. The production of some enzymes such as leucine and valine aryl-amidase was suppressed in the M medium, and the activities recovered by acclimatization treatment. The growth of some strains in the molasses medium was thus recovered by the acclimatization process, and the profiles of extracellular enzymes were also affected.

Background: Lipid disorders are one of risk factors for cardiovascular diseases. The aim of the study was to determine the lipid profile in early childhood in the group of Polish children born small for gestational age (SGA). Materials and Methods: The study included 140 children (93 SGA and 47 controls) aged 5 to 11 years. All children underwent a physical examination and blood tests for the glucose and lipid profile. SGA group was divided in subgroups: symmetrical and asymmetric intrauterine growth restriction (IUGR). Results: Blood sample analysis revealed higher levels of total cholesterol levels (SGA group 190.61 +/- 24.66 mg/dl vs control 143.23 +/- 23.90; p&lt;0.001). The analysis of particular fractions of cholesterol showed significantly higher mean values of triglycerides, LDL-cholesterol as well as lower mean values of HDL-cholesterol in children born as SGA. Children in both groups did not differ significantly according to weight and body mass index. A statistically significantly higher glucose concentration was obtained in the group of children with IUGR with symmetrical type of IUGR. Conclusions: Children born SGA even in their early childhood, without overweight or obesity, have abnormal lipid profile, which may be a risk factor of cardiovascular diseases in adulthood.

Traditional vaccines are produced by using weakened or inactivated forms of disease-causing pathogens to produce the target antigen they are designed to protect against. Messenger RNA vaccines are a class of vaccines that employ a minute segment of genetic material, known as messenger RNA (mRNA), which contains directives for the cells in the body to generate a particular protein. This genetic material is synthesized in the laboratory and packaged into a lipid nanoparticle, which protects and helps it enter cells for further protein synthesis. During vaccination with mRNA vaccine, the lipid nanoparticles containing the mRNA are injected into the muscle of vaccinees. Once inside the cells, the mRNA instructs the cells to produce a protein which is then displayed on the surface of the cell, triggering an immune response. During this, the immune system recognizes the displayed protein as foreign and mounts a defense by producing antibodies and activating immune cells to target and eliminate the protein. Furthermore, these immune responses generate a memory cell, facilitating the immune system to promptly react in case of encountering the authentic pathogen as an infection in the future. The mRNA vaccines are flexible and the sequence can be easily synthesized in the lab based on the genetic information of the target pathogen. Additionally, mRNA vaccines can be developed for new strains or variants of the target disease easily. This was particularly evident during the COVID-19 pandemic, where mRNA vaccines like the Pfizer-BioNTech and Moderna vaccines were developed and authorized for emergency use within a year. But currently, available mRNA vaccines require extensive cold chain, antigen delivery, potential immune response variability optimization, and sophisticated manufacturing process. The efforts to explore next-generation mRNA vaccine development are aimed to further improve the effectiveness, stability, and delivery methods. One focus of research has been to enhance the stability of mRNA vaccines, particularly temperature sensitivity which makes storage and distribution easier, particularly in regions with limited access to cold chain infrastructure. Self-amplifying mRNA vaccines, on the other hand, are designed to generate multiple copies of the mRNA within cells which potentially leads to a higher production of the target protein, resulting in a stronger immune response. Additionally, studies are exploring new delivery systems to improve the target and efficiency of mRNA vaccines using specialized nanoparticles and liposomes to specifically deliver mRNA to certain cell types or immune cells. Another area of interest is the development of combination vaccines, where multiple mRNA sequences are included in a single vaccine protecting against multiple diseases targeting strains or variants of a particular pathogen simultaneously. While current mRNA vaccines are administered via intramuscular injection, studies are underway to deliver directly into the skin offering enhanced immune response and the ability to use smaller vaccine doses.

Evinacumab, a human monoclonal antibody against angiopoietin-like protein 3 (ANGPTL3), has recently been approved by U.S. Food and Drug Administration as an add-on therapy for homozygous familial hypercholesterolemia (HoFH) in patients of 12 years and older. Its role as a triglyceride-lowering drug is also emerging in the literature. However, it has not been approved for this indication yet, neither in the adult nor in the pediatric population. We describe the case of a 10-year-old boy who underwent an allogeneic hematopoietic stem cell transplant for acute lymphoblastic leukemia complicated by chronic graft–versus–host disease (GVHD) and presented life-threatening refractory hypertriglyceridemia due to the concomitant use of ruxolitinib and sirolimus. After the failure of the insulin treatment and due to the technical impossibility of performing lipid apheresis, we underwent the child to evinacumab treatment, obtaining a dramatic rapid reduction in triglyceride and cholesterol levels. This is the first report of a pediatric patient younger than 12 years in Europa receiving evinacumab to treat severe hypertriglyceridemia. The therapy with angiopoietin-like proteins inhibitors has been effective, safe, and well-tolerated in our patient, suggesting that evinacumab may be used in the pediatric population when other therapeutic strategies are ineffective or contraindicated.

The current study aims to investigate the changes in polar metabolites, phenolic compounds, and fatty acids in the skin of Hass avocados stored under two distinct circumstances. Fruits from the Bartolillo orchard were primarily associated with linoleic and oleic acid as significant variables. Fruits were primarily associated with palmitoleic, palmitic, and oleic acids in Quilhuica. For one orchard, the phenolic content increased at the start of storage and declined at the conclusion, whereas the opposite was true for another, showing that the outcome was depending on the orchard and storage conditions. The polar metabolites that most closely connected with the fruits of the Quilhuica orchard were serine, glutaric acid, xylitol, and D-mannitol, whereas ß-sitosterol and gluconic were related to the fruits of the Bartolillo orchard.

The permeation of dioxin-like pollutants, namely, chlorinated dibenzodioxins and dibenzofurans, through lipid membranes has been simulated using classic molecular dynamics (CMD) combined with the umbrella sampling approach. The most toxic forms of chlorinated dibenzodioxin and dibenzofuran, 2,3,7,8-tetrachloro-p-dibenzodioxin (TCDD) and 2,3,7,8-tetrachlorodibenzofuran (TCDF), and a dioleyl-phosphatidylcholine (DOPC) lipid membrane of 50 Å wide have been chosen for our study. The free energy profile shows the penetration process is largely favoured thermodynamically (DG≈-12 kcal/mol), with a progressively decrease of the free energy until reaching the energy minima at distances of 8Å and 9.5Å from the centre of the membrane for, respectively, TCDD and TCDF. At the centre of the membrane, both molecules display subtle local maxima with free energy differences of 0.5 and 1 kcal/mol with respect to the energy minima for TCDD and TCDF, respectively. Furthermore, the intermolecular interactions between the molecules and the lipid membrane have been characterized at the minima and the local maxima using hybrid quantum mechanics/molecular mechanics energy decomposition analysis (QM/MM-EDA). Total interaction energies of -17.5 and -16.5 kcal/mol have been found at the energy minima for TCDD and TCDF, respectively. In both cases, the dispersion forces govern the molecule-membrane interactions, no significant changes have been found at the local maxima, in agreement with the classical free energy profile. The small differences found in the results obtained for TCDD and TCDF point out the adsorption and diffusion processes through the cell membrane are not related to the different toxicity shown by these pollutants.

The association of the APOE4 (vs APOE3) isoform with an increased risk of Alzheimer’s Disease (AD) is unequivocal, but the underlying mechanisms remain incompletely elu-cidated. A prevailing hypothesis incriminates the impaired ability of APOE4 to clear neurotoxic amyloid-β peptides (Aβ) from the brain as the main mechanism linking apolipoprotein isoform to disease aetiology. APOE protein mediates lipid transport both within the brain and from the brain to the periphery, suggesting that lipids may be potential co-factors in APOE4-associated physiopathology. The present study reveals several alterations in pathways of lipid homeostasis in the brains of mice expressing the human APOE4 versus APOE3 isoform. Carriers of APOE4 had deficient cholesterol turnover, an imbalance in the ratio of specific classes of phospholipids, lower levels of phosphatidylethanolamines bearing poly-unsaturated fatty acids and an overall eleva-tion in levels of monounsaturated fatty acids. These modifications in lipid homeostasis were related with increased production of Aβ peptides as well as augmented levels of tau and phosphorylated tau in primary neuronal cultures. This suite of AP-OE4-associated anomalies in lipid homeostasis and neurotoxic protein levels may be related to the accrued risk for AD in APOE4 carriers and provides novel insights into potential strategies for therapeutic intervention.

BACKGROUND: Ficus thonningii extracts exhibit hypoglycaemic, hypolipidaemic and antioxidant activities. We investigated the potential of methanolic F. thonningii stem-bark extracts (MEFT) to protect growing Sprague-Dawley (SD) against high-fructose diet-induced metabolic derangements (MD) in a model mimicking children fed obesogenic diets. METHODS: Eighty (40 males; 40 females) 21-days old SD rat pups were randomly allocat-ed to and administered, for 8 weeks, five treatment regimens: 1 - standard rat chow (SC) + water (PW), 2 - SC + 20% (w/v) fructose solution (FS), 3 - SC + FS + fenofibrate at 100 mg/kg bwt/day, 4 - SC + FS + low dose MEFT (LD; 50 mg/kg bwt/day) and 5 - SC + FS + high dose MEFT (HD; 500 mg/kg bwt/day). Body weight, glucose load tolerance, fasting blood glucose and triglyceride, plasma insulin concentration, sensitivity to insulin, liver mass and fat content, steatosis and inflammation were determined. RESULTS: Fructose had no effect on the rats’ growth, glucose and insulin concentration, glucose tolerance and insulin sensitivity (P>0.05) but increased triglycerides in females; in-duced hepatic microsteatosis and inflammation in both sexes but macrosteatosis in females (P<0.05). In females, MEFT prevented fructose-induced plasma triglyceride increase. Low dose MEFT increased liver lipid content in females (P<0.05). The MEFT protected the rats against hepatic steatosis and inflammation but fenofibrate protected against hepatic mi-crosteatosis. CONCLUSION: MEFT can be used as prophylaxis against dietary fructose-induced ele-ments of MD but caution must be taken as low dose MEFT increases hepatic lipid accretion in females predisposing to fatty liver disease.

Polyphenols have been shown to possess outstanding anti-obesity properties. In this study, the effect of blue honeysuckle berry extract (BHBE) with high polyphenol content on lipid accumulation in adipocytes and the underlying mechanism were investigated for the first time. Composition analysis demonstrated that flavonoids (mainly flavonols and anthocyanins) were the primary polyphenols in BHBE, which contributed to its biological functions. The results of Oil Red O staining combined with triglyceride (TG) content determination showed that BHBE exhibited an obvious inhibitory effect on intracellular lipid accumulation in a dose-dependent manner. BHBE also reduced the protein level of fatty acid synthase (FAS) and increased the phosphorylation level of acetyl-CoA carboxylase (ACC), indicating that lipogenesis was suppressed by BHBE treatment. Moreover, BHBE was found to significantly promote the phosphorylation of AMP-activated protein kinase (AMPK) and further reduce the expression of key transcription factors (PPARγ, C/EBPα, and SREBP-1c) that regulate lipogenesis. In addition, the expression of beige adipocyte markers (Tmem26 and Cd137) and uncoupling protein 1 (UCP1) was increased in BHBE-treated adipocytes. In summary, we consider that BHBE inhibits lipid accumulation in adipocytes by suppressing lipogenesis as well as by promoting beiging of adipocytes. These results support blue honeysuckle berry as a candidate functional food against obesity.

Viral protein 24 (VP24) from Ebola virus (EBOV) was first recognized as a minor matrix protein that associates with cellular membranes. However, more recent studies shed light on its roles in inhibiting viral genome transcription and replication, facilitating nucleocapsid assembly and transport, and interfering with immune responses in host cells through downregulation of interferon (IFN)-activated genes. Thus, whether VP24 is a peripheral protein with lipid binding ability for matrix layer recruitment has not been explored. Here we examined the lipid binding ability of VP24 with a number of lipid binding assays. The results indicated that VP24 lacked the ability to associate with lipids tested regardless of VP24 posttranslational modifications. We further demonstrate that the presence of the EBOV major matrix protein VP40 did not promote VP24 membrane association in vitro or in cells. Further, no protein-protein interactions between VP24 and VP40 were detected by co-immunoprecipitation. Confocal imaging and cellular membrane fractionation analyses in human cells suggested VP24 did not specifically localize at the plasma membrane inner leaflet. Overall, we provide evidence that EBOV VP24 is not a lipid binding protein and its presence in the viral matrix layer is likely not dependent on direct lipid interactions.

Preeclampsia (PE) is a common pregnancy complication. It is associated with high maternal morbidity and mortality rates and intrauterine foetal growth restriction. This condition is characterised by high blood pressure and urinary protein levels. Apelin and galectin-3 (Gal- 3) are peptides involved in the regulation of body fluid homeostasis, inflammation and cardiovascular functions. This study aimed to determine the correlations amongst serum apelin and Gal-3 levels and insulin resistance (IR) in women with PE. Sixty patients with PE and 30 healthy controls participated in this study. The PE group had significantly lower apelin levels (p < 0.01) and higher Gal-3 levels (p < 0.05) than the control group. The PE group had higher serum glucose levels and β-cell functions than the control group. Moreover, patients with PE exhibited dyslipidaemia. Correlation analysis indicated that apelin and Gal-3 levels were not significantly correlated. Moreover, no correlation existed between the apelin levels and any measured parameters of the PE group. In conclusion, the elevations in serum Gal-3 levels with increments in IR-related parameters and lipid profiles reflect the possible contribution of Gal-3 to the harmful effects of IR and dyslipidemia levels on women with PE.

Nanoparticles offer available tools for MDD research. In this assay, we applied CBR1 (cannabinoid receptor 1) knockout (CB1-/-) mice to study whether functionalized solid lipid nanoparticles loading with curcumin and dexanabinol (Cur/SLNs-HU-211) exhibited anti-depressant outcomes through CBR1. Wild-type (CB1+/+) animals together with CBR1 knockout (CB1-/-) animals received daily injections of Corticosterone (CORT) for 3 weeks to obtain MDD mice model, and then the therapeutic action of Cur/SLNs-HU-211 were evaluated, respectively. Our work show that Cur/SLNs-HU-211 nanoparticles in the existence of CBR1 facilitate an efficient motor function improvement in CORT-induced MDD mice model. Cur/SLNs-HU-211 nanoparticles alleviated symptoms on CB1+/+ MDD mice and resulted in dopamine and norepinephrine recovery following CORT-induced neurotoxicity. In conclusion, the possible mechanisms underlying the antidepressant effect of Cur/SLNs-HU-211 might be the induction of CB1 expression and downstream RASGEF1C and Egr1 expression, together with a significantly upregulation of neuron-specific genes in CB1+/+ mice only. In conclusion, CBR1 is necessary during the process of antidepressant activities of Cur/SLNs-HU-211 nanoparticles. This study confirms that Cur/SLNs-HU-211 nanoparticles based CBR1 in vivo targeting would be a potentially feasible and safe way to motivate future therapeutic strategies of Major Depressive Disorder.

Abstract: Background and objective: Propofol is an anesthetic agent that is frequently used in anesthesia induction, maintenance and sedation. Propofol has severe side effects such as hypotension, bradycardia and respiratory depression. Although propofol is commonly used, there is no known antidote for its toxic effects. An approach to prevent toxic effects of propofol would be beneficial. The aim of this study was to assess the effects of intravenous lipid emulsion (ILE) therapy in the prevention of depressive effects of propofol on cardiovascular and respiratory systems. Materials and methods: Twenty-eight Sprague-Dawley adult rats were randomly divided into 4 groups. The saline-administered group was determined as the Control group. The second group was administered propofol (PP group); the third group was administered ILE (ILE group), and the fourth was administered propofol with ILE therapy (ILE+PP group). Systolic blood pressure (SBP), Diastolic blood pressure (DBP), Mean arterial blood pressure (MAP), Respiratory rate (RR), Heart rate (HR) and mortality were recorded at 10 points during 60 minutes. A repeated measures linear mixed-effect model with unstructured covariance was used to compare the groups. Results: In the PP group, SBP, DBP, MAP, RR and HR levels were declining steadily; all rats in this group died after 60 minutes. In the ILE+PP group, after a while, the decreased SBP, DBP, MAP, RR and HR levels increased SBP, DBP, MAP, RR and HR levels of the Propofol group were found to be significantly lower than those of the other groups (p<0.01). The mortality rate was 100% (surviving period, 60 min) for the PP group, whereas 0% for the ILE, ILE+PP and Control groups. Conclusion: Our results suggest that undesirable side effects that can be seen after propofol application such as hypotension, bradycardia and respiratory depression might be prevented by using ILE therapy.

In recent years, Atherosclerotic Cardiovascular Disease (ACVD), Obesity and Diabetes, have increase exponentially worldwide. In the present work, we evaluate the genoprotective effect of consuming a flavonoids-rich chocolate and the improvement in the biochemical parameters related to the prevention and treatment of cardiovascular risk and metabolic syndrome in young Mexican adults. A randomized, placebo-controlled, double-blind study was undertaken in the Autonomous University of Baja California. The treatments were a daily intake of 2 grams of dark chocolate containing 70% cooca or milk chocolate. Total phenolic compounds and flavonoids were evaluated in both chocolates. Anthropometrical and Biochemical parameters were measured in the 84 participants before and after the study. Buccal epithelial genotoxicity was also evaluated from the beginning to the end of the experiment in the participants. Result suggested that flavonoids of cocoa intake have protective effects against DNA damage, and Biochemical parameters (total cholesterol, triglycerides, and LDL-cholesterol level in blood) and anthropometrical parameters (waist circumference) were also improved after six months of daily intake of 2 grams of dark chocolate with a 70% of cocoa.

The cyclic AMP-responsive element-binding protein H (CREBH, encoded by CREB3L3) is a membrane-bound transcriptional factor that primarily localizes in the liver and small intestine. CREBH governs triglyceride metabolism in the liver, which mediates the changes in gene expression governing fatty acid oxidation, ketogenesis, and apolipoproteins upregulating LPL activity. A deficiency of CREBH in mice leads to severe hypertriglyceridemia. CREBH, in synergy with PPARα, has a crucial role in upregulating Fgf21 expression, which is implicated in metabolic homeostasis. CREBH binds to and functions as a co-activator for both PPARα and LXRα in regulating gene expression of lipid metabolism. Furthermore, intestinal CREBH in overexpression reduces cholesterol absorption and suppresses high-cholesterol diet-induced fatty liver. Conversely, a deficiency of CrebH in mice fed on various high-fat diets leads to severe fatty liver. Thus, CREBH could be a therapeutic target in the treatment of metabolic diseases.

Aspalathin, a C-glucosyl dihydrochalcone, has previously been shown to protect cardiomyocytes against hyperglycemia-induced shifts in substrate preference and subsequent apoptosis. However, the precise gene regulatory network remains to be elucidated. To unravel the mechanism and provide insight into this supposition, the direct effect of aspalathin in an isolated cell-based system, without the influence of any variables, was tested using an H9c2 cardiomyocytes model. Cardiomyocytes were exposed to high glucose (33 mM) for 48 hours before post-treatment with or without aspalathin. Thereafter, RNA was extracted and RT2 PCR Profiler Arrays were used to profile the expression of 336 genes. Results showed that, 57 genes were differentially regulated in the high glucose or high glucose and aspalathin treated groups. STRING analysis revealed lipid metabolism and molecular transport as the biological processes altered after high glucose treatment, followed by inflammation and apoptosis. Aspalathin was able to modulate key regulators associated with lipid metabolism (Adipoq, Apob, Cd36, Cpt1, Pparγ, Srebf1/2, Scd1 and Vldlr), insulin resistance (Igf1, Akt1, Pde3 and Map2k1), inflammation (Il3, Il6, Jak2, Lepr, Socs3, and Tnf13) and apoptosis (Bcl2 and Chuk). Collectively, our results propose that aspalathin could reverse metabolic abnormalities by activating Adipoq while modulating the expression of Pparγ and Srebf1/2, decreasing inflammation via Il6/Jak2 pathway, which together with an observed increased expression of Bcl2 prevents myocardium apoptosis.

Heart failure is a prevalent cardiovascular condition with significant health implications, necessitating effective diagnostic strategies for timely intervention. This study explores the potential of continuous monitoring of non-invasive signals, specifically integrating Photoplethysmogram (PPG) and Electrocardiogram (ECG), for enhancing early detection and diagnosis of heart failure. Leveraging a dataset from the MIMIC-III database, encompassing 682 heart failure patients and 954 controls. Feature selection techniques were used to systematically select key features which were identified for their clinical relevance and significance in capturing cardiovascular dynamics and to reduce computational complexity and to decrease the chance of overfitting the ML algorithms. These features are then utilized to train and evaluate machine learning algorithms, resulting in a model with an impressive accuracy of 98%, sensitivity of 97.60%, specificity of 96.90%, and precision of 97.20%. The integrated approach outperforms single-signal strategies, showcas-ng its potential for early, precise, and non-invasive heart failure diagnosis. Furthermore, the study underscores the significance of continuous monitoring through wearables, emphasizing the benefits of integrating multiple signals for a comprehensive evaluation of cardiovascular health. The proposed approach holds promise for implementation in hardware systems to enable continuous monitoring, aiding in early detection and prevention of critical health conditions.

Background: Autonomic neuropathy commonly arises as a long-term complication in end stage kidney disease (ESKD) and can be diagnosed from heart rate variability (HRV), calculated from electrocardiogram (ECG) recordings. There is limited data about HRV using real-time ECG to predict HD efficiency in patients with ESKD who are routinely doing HD in real-world practice. Methods: Total of 50 patients (62.1 ± 10.7 years) with ESKD underwent continuous real-time ECG monitor (237.4 ± 15.3 min) during HD for HRV using remote monitoring system and checked electrolyte levels before/after HD. And we compared HRV according to electrolyte levels. Results: During the monitor, we checked total 2374 times of ECG and electrolyte level simultaneously of all patients. Both time and frequency domain HRV were higher when the patients had lower K+ level (&lt;0.5 mEq/L) and P+ level change (&lt;2 mEq/L) before/after HD as compared with those with higher K+ level (≥0.5 mEq/L) and P+ level (≥2 mEq/L) change respectively. In addition, there were higher incidence of arrhythmic events including atrial/ventricular premature complexes, even though no difference of mean heart rate in patients with lower K+ and P+ level change group (p &lt; 0.001). Conclusions: Higher HRV was independently associated with poor controlled K+ and P+ level during hemodialysis in patients with ESKD. This is further substantiated by independent continuous associations between real-time measures of higher HRV and K+ and P+ level. These data strongly suggest that cardiac autonomic dysfunction can be caused by lower change of electrolytes before/after hemodialysis alone.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an emerging infectious disease with currently a pandemic state. Cardiac function can be involved, affecting prognosis, in addition with lung feature severity, particularly in patients with comorbidities. Since the renin angiotensin aldosterone (RAA) system may interact with SARS-Cov-2, researches are still ongoing to assess the prognostic value of RAA blockers in cardiology.

Congestive heart failure (CHF) is a major cause of morbidity and mortality with an increasing prevalence in human and canine populations. Similar to humans, overactivation of the renin-angiotensin aldosterone system is involved in the pathophysiology of CHF in dogs. Current therapeutic strategies for the management of canine CHF include the use of RAAS inhibitors, diuretics and inodilators. The present review summarizes data from our own research on the modulation of the renin-angiotensin cascade in dogs in dogs, together with new findings (including novel therapeutic targets) from the veterinary and the human literature.

Heart failure (HF) has several etiologies including myocardial infarction (MI) and left ventricular remodeling (LVR), but its progression remains difficult to predict in clinical practice. Systems biology analyses of LVR after MI predict molecular insights of this event such as modulation of microRNA (miRNA) that could be used as a signature of HF progression. To define a miRNA signature of LVR after MI, we use 2 systems biology approaches integrating either proteomic data generated from LV of post-MI rat induced by left coronary artery ligation or multi-omics data (proteins and non-coding RNAs) generated from plasma of post-MI patients from the REVE-2 study. The first approach predicts 13 miRNAs and 3 of these miRNAs were validated to be associated with LVR in vivo: miR-21-5p, miR-23a-3p and miR-222-3p. The second approach predicts 24 miRNAs among 1310 molecules and 6 of these miRNAs were selected to be associated with LVR in silico: miR-17-5p, miR-21-5p, miR-26b-5p, miR-222-3p, miR-335-5p and miR-375. We identified a signature of 7 microRNAs associated with LVR after MI that support the interest of integrative systems biology analyses to define a miRNA signature of HF progression.

Hedgehog (Hh) proteins are prototypical morphogens known to regulate epithelial/mesenchymal interactions during embryonic development. In addition to its pivotal role in embryogenesis, the Hh signaling pathway may be recapitulated in post-natal life in a number of physiological and pathological conditions, including ischemia. This review highlights the involvement of Hh signaling in ischemic tissue regeneration and angiogenesis, with particular attention to the heart, the brain, and the skeletal muscle. Updated information on the potential role of the Hh pathway as a therapeutic target in ischemic condition is also presented.

Background and objectives: The correlation of cardiac troponin I with early in-hospital outcomes in acute myocardial infarction is not well established. This study aims to assess the role of troponin I in predicting in-hospital outcomes and early left ventricular systolic dysfunction in patients with ST-segment elevation myocardial infarction (STEMI). Patients and methods: In a prospective study, 116 patients (74males and 42 females), with STEMI who had been admitted to the Coronary CareUnit from March 2015 to September 2015 were enrolled. Patients were divided according to the level of troponin I on admission into 3 groups (low, medium and high elevation). Results: The mean age (+ SD) of the patients was 60+11.4 years. The troponin level of 66.2% of males was high compared with 52.4% of females (p=0.002). The incidence of acute pulmonary edema (21.1%), cardiogenic shock (7%) and early left ventricular systolic dysfunction (49.3%) was significantly higher among patients with high troponin level compared with (0%, 0% and 16%, respectively) among patients with low troponin level. All deaths and cardiac arrest were of high troponin level. Conclusions: High admission troponin I in STEMI permits early identification of patients at increased risk of major cardiac complications and death.

Background According to some authors, a single isolated measurement of serum BNP executed on hospital admission would not be a sufficiently accurate method to predict the outcome of patients with ADHF. Aims For verifying this assumption, a retrospective study was conducted on patients hospitalized for ADHF. Our main objective was to ascertain whether there was any difference in midterm mortality among patients with rising BNP at discharge as compared to those with decreasing BNP at discharge. Methods Medical records were examined so as to make a partition of the ADHF patient population into two groups, the former characterized by a rise in BNP during hospitalization, and the latter exhibiting a decrease in BNP in the measurement taken at hospital discharge. Results 177 patients were enrolled in a retrospective study. Among them, 53 patients (29.94%) had increased BNPs at the time of discharge, whereas 124 (70.06%) showed decreases in serum BNP during their hospital stay. The group with patients who exhibited BNP increases at the time of discharge had higher degree of congestion evident in the higher frequency of persistent jugular venous distention and persistent orthopnea at discharge. Moreover, patients with increased BNP at the time of discharge had a lower reduction in inferior vena cava maximum diameter [1.58 ± 2.2 mm vs. 6.32 ± 1.82 mm; p (one-way ANOVA)=0.001]. In contrast, there was no significant difference in weight loss when patients with increased BNP at discharge were compared to those with no such increase. A total of 14 patients (7.9%) died during the six-month follow-up period. Cox proportional hazard analysis revealed that BNP increase at the time of discharge was an independent predictor of six-month all-cause mortality after adjustment for age, sodium at discharge, creatinine at discharge and New York Heart Association (NYHA) class at discharge (hazard ratio 34.49; 95% confidence intervals: 4.55–261.06; P =0.001). Conclusions Among patients with history of ADHF, more elevated BNP levels at the time of discharge from the hospital compared to those detected at admission identify a patient subset with higher grade of congestion and higher six-month mortality.

Primary care pediatricians encounter a wide range of complex conditions in their daily clinical practice. It is not uncommon for their patients to get exposed to medical errors. Diagnostic errors, defined as missed, delayed, or wrong diagnosis, are of great importance as they may cause significant harm to the pediatric patient with severe disease. These errors often occur when the symptoms and signs of a disease are atypical or missing. Data on the most frequent misdiagnosed situations in pediatrics is scarce. One of these groups of conditions is that regarding cardiac diseases. The pediatric cardiology field has met rapid development over the past few decades. Primary care providers play a key role in diagnosis, management, and referral of children with heart disease, both congenital and acquired, because many common cardiac complaints are first addressed in the primary care setting. The scope of this review is to investigate the cardiac entities that are often missed by the general pediatricians. In particular, it aims to spot the most common of them, to describe their clinical presentation, their diagnostic options, red flags, and tips, and to provide the ways to avoid erroneous, delayed, or missed diagnosis.

New insights into the causes and mechanisms of congenital heart disease (CHD) have been gained through the use of next-generation sequencing. Examination of the whole exome sequence detects detrimental gene variations modifying single or contiguous nucleotides, that are characterised as pathogenicity based on statistical assessments of families. and correlates with congenital heart disease, elevated expression during heart development, and reduction of harmful protein-coding mutations in the general population. Patients with CHD and extracardiac abnormalities enriched for gene classes meeting these criteria. CHDs and extracardiac defects, supporting a common set of pathways in the organogenesis of CHDs. Single-cell transcriptomics data reveal the expression of genes associated with CHD in specific cell lineages, and emerging evidence suggests that genetic variants disrupt multicellular genes essential for cardiogenesis. Metrics and units are being tracked in whole genome sequence studies.

The aim of the study was to assess the impact of two lengths of Nordic walking (NW) training interventions combined with time restricted eating (TRE) on improving body composition parameters, lipid profile, and levels of selected adipokines in women with disrupted body mass. Overweight and obese women (n=55, age: 21-85) were recruited. Four groups were selected: 6 weeks (SG6, n=13) and 12 weeks intervention (SG12, n=13); and two control groups: CON6 (n=13); and CON12 (n=13). The training sessions took place 3 times a week (60 minutes each) and were conducted outdoor under the supervision of professional coach. The training intensity was determined individually. The extended NW program combined with TRE induced a significant weight reduction in SG12 by 1.96 kg (p=0.010) and fat tissue by 1.64 kg (p=0.05). The proposed interventions did not affect LBM, TBW [kg], VFA and lipid profile. The LDL/HDL ratio changed with small size effect. Leptin concentration differed between groups (p=0.006), but not over time. For resistin, the differentiating factor was time (p=0.019, with lower results observed after the intervention). The change in leptin concentration was negatively correlated with its baseline concentration. Extended to 12 weeks, this intervention allows for an improvement in body composition. Neither 6 nor 12 weeks of training and fasting affected the lipoprotein profile.

PCSK9 is implicated in familial hypercholesterolemia via targeting the cell surface PCSK9-LDLR complex toward lysosomal degradation. The M2 repeat in the PCSK9's C-terminal domain is essential for its extracellular function, potentially through its interaction with an unidentified “protein X”. The M2 repeat was recently shown to bind an R-x-E motif in MHC-class-I proteins (implicated in the immune system), like HLA-C, and causing their lysosomal degradation. These findings suggested a new role of PCSK9 in the immune system and that HLA-like proteins could be “protein X” candidates. However, the participation of each member of the MHC-I protein family in this process and their regulation of PCSK9's function have yet to be determined. Herein, we compared the implication of MHC-I-like proteins such as HFE (involved in iron homeostasis) and HLA-C on the extracellular function of PCSK9. Our data revealed that the M2 domain regulates the intracellular sorting of the PCSK9-LDLR complex to lysosomes, and that HFE is a new target of PCSK9 that inhibits its activity on the LDLR, whereas HLA-C enhances its function. This work suggests the potential modulation of the PCSK9 functions through interactions of HFE and HLA-C.

Aging and obesity make humans more prone to cardiovascular and metabolic syndrome diseases, leading to several serious health conditions, including dyslipidemia, high blood pressure, and sleep disturbance. Hyperlipidemia means elevated blood lipid levels, including cholesterol and triglycerides. This study aimed to explore the hypolipidemic effect of fermented citrus lemon juice using a hyperlipidemic hamster model. Sugar-free lemon juice’s fermentation was optimized, and the characteristics of fresh and fermented lemon juice (FLJ) were evaluated and compared. In addition, tests were conducted to determine the appropriate hamster feed for the functional animal tests. Then, experiments were conducted to evaluate the hypolipidemic effect of the FLJ, which contained polyphenols and superoxide dismutase-like activity, on a hyperlipidemic hamster model. This study’s pre-fermentation efficiency evaluation found that 21–30 days of bacterial DMS32004 and DMS32005 fermentation of fresh lemon juice provided the best fermentation benefits. In addition, the fermentation evaluation showed that a sugar-free fermentation method provided FLJ with the best benefits. Results showed that the absorption and utilization efficiency of FLJ was higher compared with the unfermented lemon juice. After six weeks of feeding, the total cholesterol and triglyceride values in the blood and liver of the FLJ treatment groups were de-creased compared with the high-fat diet (HFD) group. In addition, the blood low-density lipoprotein cholesterol levels were significantly reduced in the FLJ treatment groups compared with the HFD group. In contrast, the blood high-density lipoprotein to low-density lipoprotein cholesterol ratio increased considerably in the FLJ treatment groups, and the total to high-density lipoprotein ratio was significantly lower than in the HFD group. Compared with the HFD group, the total cholesterol content in the FLJ treatment groups’ feces increased significantly. This study demonstrated that the sugar-free fermentation method and fermentation cycle management provided FLJ with the potential to regulate blood lipids. Further research and verification will be carried out to isolate specific substances from the FLJ and identify their mechanisms of action.

Objective To observe the effect of roxadustat on blood pressure and micro-inflammatory response in patients with hemodialysis anemia, and to provide a viable technique for the treatment of hemodialysis anemia patients. Methods A total of 100 hemodialysis anemia patients admitted to the Nephrology Department of our hospital from July 2020 to July 2021 were enrolled and randomly divided into an observation group (roxadustat) and a control group (human recombinant erythropoietin (rhEPO). The clinical efficacy, blood lipid metabolism, inflammatory factor levels, iron metabolism-related indicators, blood biochemical indicators, anemia indicators, adverse reactions and blood pressure were recorded and compared. Results There was no significant difference in baseline data and serum indicators (P>0.05). The study group demonstrated superior performance to the control group in terms of clinical efficacy, blood lipid metabolism, inflammatory factor levels, iron metabolism-related indicators, blood biochemical indicators, anemia indicators, adverse reactions and blood pressure (all P<0.05). Conclusion Compared with rhEPO treatment, roxadustat exhibits a promising outcome in treating anemia and has slight impact on blood pressure of patients.

Phospholipases are among the important elements involved in lipid-dependent cell signaling that lead to the induction of downstream pathways. In the current study, phospholipases D (PLDs) gene family was characterized and compared in two important oilseeds crops, Brassica napus and Camelina sativa. The results revealed that PLD has 33 members in Camelina sativa (CsPLD) and 41 members in Brassica napus (BnPLD). All studied PLDs showed a negative GRAVY value, indicating that PLDs are probably hydrophilic proteins. Phylogenetic analysis separated PLDs into five subfamilies; gamma, delta, beta, alpha, and zeta. According to evolution analysis, a different evolution process was observed between CsPLD and BnPLD. In addition, the results disclosed that the most of the PLD genes have been segmentally duplicated under purifying selection. Cis-regulatory elements related to ABA and auxin responsiveness were more found in upstream region of CsPLDs, while elements linked with MeJA responsiveness were more dis-tributed in promoter region of BnPLDs. Analysis of the expression data showed that PLD alpha genes have a wide expression and are expressed in most tissues. Quantitative expression analysis (qPCR) of CsPLD genes under salt stress, 200 mM of NaCl, was done in different time series. The results revealed that the CsPLD genes are involved in the response to salinity stress and their expression levels enhance with the increase of salinity stress time. The outcomes of this research will be useful for future molecular work related to lipid signaling in oilseed plants.

As abiotic stress, drought limits plant growth and minimizes productivity. The increased request for valuable essential oil extracted from geranium (Pelargonium graveolens L.) is mainly associated with plant growth, which is adversely affected by drought. Melatonin (MT) has been used to enhance plant growth under abiotic stress, however, its impact to overcome drought stress of aromatic plants including geranium is poorly investigated. In the current investigation, MT application at 100 µM was applied under 100 % (well-watered) or 50 % (drought stress) of FC to verify this role. Drought stress markedly reduced growth parameters, herb yield, and total chlorophyll; however, MT alleviated these effects. In contrast, drought enhanced the essential oil percentage in geranium leaves. Despite the reduction in oil yield caused by drought, MT application mitigated this reduction and improved both oil yield and oil components. Besides, MT treatment enhanced the accumulation of total phenols, glutathione, and proline and improved the activity of ascorbate peroxidase, catalase, and glutathione reductase with possible alleviation of drought-induced oxidative damage. Therefore, it reduced both H2O2 and malondialdehyde accumulation, and finally maintained membrane integrity. Overall, this is the first report that reveals that MT application can improve geranium resistance to drought by enhancing the antioxidant potential and protecting the cell membrane from oxidative damage.

In the contemporary era, there has been a notable surge in the systematic utilization of therapeutic drugs that exhibit stimulus-responsive drug release patterns in specific target areas. However, challenges such as premature drug release and limited biocompatibility persist. To address these issues, the application of a lipid coating on mesoporous silica nanoparticles (MSNs) has emerged as a promising strategy. This lipid coating not only enhances the stability and biocompatibility of nanocarriers but also facilitates targeted drug delivery to diseased cells while minimizing drug release throughout the body. MSNs, renowned for their unique attributes including high porosity, morphology, and controllable pore size, have been widely recognized as suitable platforms for drug/gene delivery systems. Furthermore, graphene-based nanomaterials such as graphene oxide and reduced graphene oxide have garnered significant interest in the fields of biology and biomedicine. These materials possess exceptional characteristics such as a large surface area, distinct surface properties, high biocompatibility, and pH sensitivity, making them ideal candidates for incorporating drugs, genes, photosensitizers, and other cargo to design innovative drug delivery systems. This study aims to emphasize the ongoing efforts and advancements in enhancing the capacity and versatility of nanocomposites comprising graphene MSN composites for applications in drug delivery.

Agaricus bisporus is well known as a source of polysaccharides that could improve human health. The objective of this study was to explore anti-obesity effect of A. bisporus extract (H2Oslim®) abundant in polysaccharides and its underlying mechanism. Pancreatic lipase inhibitory activity in vitro was determined after treatment with H2Oslim® and chitosan. Treatment with H2Oslim® and chitosan significantly decreased pancreatic lipase activity. Five-week-old male SD rats were randomly divided into three groups for acute feeding with vehicle, H2Oslim® at 80 mg/kg body weight (BW)/day, and H2Oslim® at 160 mg/kg BW/day. H2Oslim® does-dependently increased plasma lipid clearance in an oral lipid tolerance test. Five-week-old male C57BL/6N mice were fed a control diet (CD), a high fat diet (HFD), an HFD with H2Oslim® at 80 mg/kg BW/day, H2Oslim® at 160 mg/kg BW/day, or chitosan at 160 mg/kg BW/day for eight weeks. HFD-fed mice showed significant increases of body weight, fat mass, white adipose tissue, average lipid droplet size, and serum levels of glucose, triglyceride, ALT, and AST compared to those in the CD group. However, H2Oslim® or chitosan administration ameliorated these increases. H2Oslim® or chitosan signifi-cantly reduced dietary efficiency and increased fecal excretion levels of lipid, triglyceride, and total cholesterol. These in vitro and in vivo findings suggest that H2Oslim® might act as an anti-obesity agent by inhibiting pancreatic lipase-mediated lipid absorption, at least in part.