Optimization and Synthesis of Nano-Niosomes for Encapsulation of Triacontanol by Box-Behnken Design.

Triacontanol is a long-chain primary alcohol derived from policosanol, known for its diverse biological activities, including functioning as a plant growth regulator and exhibiting anti-inflammatory and antitumoral effects. However, its application is limited due to its high hydrophobicity, resulting in poor absorption and reduced therapeutic effectiveness. A potential solution to this problem is the use of niosomes. Niosomes are carriers composed of non-ionic surfactants, cholesterol, charge-inducing agents, and a hydration medium. They are effective in encapsulating drugs, improving their solubility and bioavailability. The objective of this study was to optimize and synthesize nano-niosomes for the encapsulation of triacontanol. Niosomes were synthesized using a thin-film hydration method combined with ultrasonication, following a Box-Behnken design. Niosomes were characterized using various techniques including dynamic light scattering, Fourier-transform infrared spectroscopy (FTIR), confocal microscopy, high-resolution scanning electron microscopy, and transmission electron microscopy (TEM). Formulation 14 of niosomes achieved the desired size, polydispersity index (0.198 ± 0.008), and zeta potential (-31.28 ± 1.21). FTIR analysis revealed a characteristic signal in the 3400-300 cm-1 range, indicating intermolecular interactions due to a bifurcated hydrogen bond between cholesterol and S60. Confocal microscopy confirmed the presence of triacontanol through Nile Red fluorescence. TEM revealed the spherical structure of niosomes.

Capsaicin Improves Systemic Inflammation, Atherosclerosis, and Macrophage-Derived Foam Cells by Stimulating PPAR Gamma and TRPV1 Receptors.

BACKGROUND: Capsaicin, a bioactive compound found in peppers, is recognized for its anti-inflammatory, antioxidant, and anti-lipidemic properties. This study aimed to evaluate the effects of capsaicin on atherosclerosis progression. METHODS: Apolipoprotein E knockout mice and their C57BL/6 controls were utilized to assess blood lipid profile, inflammatory status, and atherosclerotic lesions. We also examined the influence of capsaicin on cholesterol influx and efflux, and the role of TRPV1 and PPARγ signaling pathways in bone marrow-derived macrophages. RESULTS: Capsaicin treatment reduced weight gain, visceral adiposity, blood triglycerides, and total and non-HDL cholesterol. These improvements were associated with a reduction in atherosclerotic lesions in the aorta and carotid. Capsaicin also improved hepatic oxidative and inflammatory status. Systemic inflammation was also reduced, as indicated by reduced leukocyte rolling and adhesion on the mesenteric plexus. Capsaicin decreased foam cell formation by reducing cholesterol influx through scavenger receptor A and increasing cholesterol efflux via ATP-binding cassette transporter A1, an effect primarily linked to TRPV1 activation. CONCLUSIONS: These findings underscore the potential of capsaicin as a promising agent for atherosclerosis prevention, highlighting its comprehensive role in modulating lipid metabolism, foam cell formation, and inflammatory responses.

In silico comparative analysis of cestode and human NPC1 provides insights for ezetimibe repurposing to visceral cestodiases treatment.

Visceral cestodiases, like cysticercoses and echinococcoses, are caused by cystic larvae from parasites of the Cestoda class and are endemic or hyperendemic in many areas of the world. Current therapeutic approaches for these diseases are complex and present limitations and risks. Therefore, new safer and more effective treatments are urgently needed. The Niemann-Pick C1 (NPC1) protein is a cholesterol transporter that, based on genomic data, would be the solely responsible for cholesterol uptake in cestodes. Considering that human NPC1L1 is a known target of ezetimibe, used in the treatment of hypercholesterolemia, it has the potential for repurposing for the treatment of visceral cestodiases. Here, phylogenetic, selective pressure and structural in silico analyses were carried out to assess NPC1 evolutive and structural conservation, especially between cestode and human orthologs. Two NPC1 orthologs were identified in cestode species (NPC1A and NPC1B), which likely underwent functional divergence, leading to the loss of cholesterol transport capacity in NPC1A. Comparative interaction analyses performed by molecular docking of ezetimibe with human NPC1L1 and cestode NPC1B pointed out to similarities that consolidate the idea of cestode NPC1B as a target for the repurposing of ezetimibe as a drug for the treatment of visceral cestodiases.

Involvement of Expression of miR33-5p and ABCA1 in Human Peripheral Blood Mononuclear Cells in Coronary Artery Disease.

MicroRNAs (miRs) are small non-coding RNAs that regulate gene expression post-transcriptionally and are crucial in lipid metabolism. ATP-binding cassette transporter A1 (ABCA1) is essential for cholesterol efflux from cells to high-density lipoprotein (HDL). Dysregulation of miRs targeting ABCA1 can affect cholesterol homeostasis and contribute to coronary artery disease (CAD). This study aimed to investigate the expression of miRs targeting ABCA1 in human monocytes, their role in cholesterol efflux, and their relationship with CAD. We included 50 control and 50 CAD patients. RT-qPCR examined the expression of miR-33a-5p, miR-26a-5p, and miR-144-3p in monocytes. Logistic regression analysis explored the association between these miRs and CAD. HDL's cholesterol acceptance was analyzed using the J774A.1 cell line. Results showed that miR-26a-5p (p = 0.027) and ABCA1 (p = 0.003) expression levels were higher in CAD patients, while miR-33a-5p (p < 0.001) levels were lower. Downregulation of miR-33a-5p and upregulation of ABCA1 were linked to a lower CAD risk. Atorvastatin upregulated ABCA1 mRNA, and metformin downregulated miR-26a-5p in CAD patients. Decreased cholesterol efflux correlated with higher CAD risk and inversely with miRs in controls. Reduced miR-33a-5p expression and increased ABCA1 expression are associated with decreased CAD risk. miR deregulation in monocytes may influence atherosclerotic plaque formation by regulating cholesterol efflux. Atorvastatin and metformin could offer protective effects by modulating miR-33a-5p, miR-26a-5p, and ABCA1, suggesting potential therapeutic strategies for CAD prognosis and treatment.

Effect of seminal plasma cholesterol and triacylglycerides concentrations and sperm morphology on semen freezability in domestic cats (Felis silvestris catus).

There is scarce information about the effect of sperm morphology and seminal plasma composition on cat semen freezability. Thus, this study aims to assess the effect of cat sperm morphology and seminal plasma cholesterol (CHOL) and triacylglyceride (TAG) concentrations on sperm post-thaw survival. Ejaculates (n = 49) were evaluated, and seminal plasma was separated and frozen until CHOL and TAG concentrations were measured. The sperm pellet was diluted in a tris-based egg yolk extender, frozen (n = 38), or processed for sperm ultrastructure study (n = 11). Abnormalities recorded were abnormal head shape and size, detached heads, knobbed or ruffled acrosomes, eccentric mid-piece insertion, proximal and distal cytoplasmic droplets, folded and coiled tails, and Dag defect. Ultramicroscopic evaluation detected several sperm abnormalities in fresh semen and some sperm damage in frozen semen. Seminal plasma lipids components were positively correlated with post-thaw motility and acrosome integrity. Higher freezability indices for motility and acrosome integrity were observed in frozen-thawed semen with high seminal plasma CHOL and TAG concentrations. No freezability differences were observed between teratozoospermic and normozoospermic ejaculates. Our results showed that even when seminal plasma was removed before cryopreservation, sperm survival after thawing was significantly higher in samples with high seminal plasma CHOL and TAG concentrations, indicating a rapid adherence to these compounds to the sperm plasma membrane, protecting sperm cells from temperature changes. Nevertheless, there were no differences in sperm freezability by sperm morphology.

Neurolipidomics in schizophrenia: A not so well-oiled machine.

Most patients with schizophrenia (SCZ) do not exhibit violent behaviors and are more likely to be victims rather than perpetrators of violent acts. However, a subgroup of forensic detainees with SCZ exhibit tendencies to engage in criminal violations. Although numerous models have been proposed, ranging from substance use, serotonin transporter gene, and cognitive dysfunction, the molecular underpinnings of violence in SCZ patients remains elusive. Lithium and clozapine have established anti-aggression properties and recent studies have linked low cholesterol levels and ultraviolet (UV) radiation with human aggression, while vitamin D3 reduces violent behaviors. A recent study found that vitamin D3, omega-3 fatty acids, magnesium, and zinc lower aggression in forensic population. In this review article, we take a closer look at aryl hydrocarbon receptor (AhR) and the dysfunctional lipidome in neuronal membranes, with emphasis on cholesterol and vitamin D3 depletion, as sources of aggressive behavior. We also discuss modalities to increase the fluidity of neuronal double layer via membrane lipid replacement (MLR) and natural or synthetic compounds. This article is part of the Special Issue on "Personality Disorders".

Metabolic effects of physical exercise on zebrafish (Danio rerio) fed a high-fat diet.

The present study aimed to establish zebrafish as an experimental model for investigations into obesity and physical exercise, as well as to assess the effects of these factors on metabolism. The experiment spanned twelve weeks, comprising a feeding trial during which the last four weeks incorporated a physical exercise protocol. This protocol involved placing fifteen animals in a five-liter aquarium, where they were subjected to swimming at an approximate speed of 0.08 m/s for 30 min daily. Throughout the experiment, histological analyses of visceral, subcutaneous, and hepatic adipose tissues were conducted, along with biochemical analyses of total cholesterol and its fractions, triglycerides, glucose, lactate, and alanine aminotransferase (ALT) levels. Additionally, oxidative stress markers, such as reactive oxygen species (ROS) levels, superoxide dismutase (SOD) activity, and catalase activity and the formation of thiobarbituric acid-reactive substances, were investigated. The results revealed that the group fed a high-fat diet exhibited an increase in ROS production and SOD activity. In contrast, the group administered the high-fat diet and subjected to physical exercise demonstrated a notable reduction in visceral adipocyte area, hepatic steatosis levels, ALT levels, and SOD activity. These findings indicate that physical exercise has a positive effect on obesity and oxidative stress in zebrafish, providing promising evidence for future investigations in this field.

Inclusion of cocoa bran in the diet of lambs and its effect on reproductive parameters.

The objective of the study was to evaluate the effect of the inclusion of cocoa bran in the diet of lambs and its effect on reproductive parameters. For this, 40 lambs were randomly assigned to four treatments, and including 0, 10, 20 and 30% levels of cocoa bran in the concentrate. Blood was collected to measure cholesterol and testosterone and semen for physical and morphological evaluation; testicular biometry and morphometry were also evaluated. There was significant difference (P < 0.05) in body weight and tubulosomatic index between the lambs in the control treatment and those in the 30% cocoa bran treatment. There was no difference in testicular biometry, physical and morphological parameters of fresh semen, testicular morphometry, and volumetric ratio between lambs in all the treatments (P < 0.05). In addition, there was no difference in plasma cholesterol or testosterone concentration (P > 0.05). Thus, it is possible to include up to 30% of cocoa bran in diet without affecting the reproductive parameters of lambs.

Very Low Calorie Ketogenic Diet: What Effects on Lipid Metabolism?

PURPOSE OF REVIEW: This review aims to critically examine how VLCKD affects plasma lipoprotein, lipid and cholesterol metabolism. Cardiovascular disease is a worldwide health problem affecting millions of people and leading to high rates of mortality and morbidity. There is a well-established association between cardiovascular disease and circulating cholesterol. Various dietary recommendations are currently available for the management of dyslipidemia. RECENT FINDINGS: The very low-calorie ketogenic diet (VLCKD) is becoming increasingly popular as a treatment option for several pathological conditions, including dyslipidemia. In addition to being low in calories, the VLCKD's main feature is its unique calorie distribution, emphasizing a reduction in carbohydrate consumption in favor of fat as the primary calorie source. Lowering calorie intake through a VLCKD can reduce the endogenous production of cholesterol. However, if the foods consumed are from animal sources, dietary cholesterol intake may increase due to the higher fat content of animal products. When combined, these dietary practices may have opposing effects on plasma cholesterol levels. Studies investigating the impact of VLCKD on plasma cholesterol and low-density lipoprotein cholesterol levels report contradictory findings. While some studies found an increase in low-density lipoprotein cholesterol levels, others showed a decrease in total cholesterol and low-density lipoprotein cholesterol, along with an increase in high-density lipoprotein cholesterol.

Growth and physiological response of proactive and reactive juvenile "tambaqui" (Colossoma macropomum) in a recirculating aquaculture system.

This study evaluated the growth and physiological response of proactive and reactive Colossoma macropomum juveniles in a recirculating aquaculture system (RAS). In Phase 1 of the experiment (50 days of cultivation), juveniles, weighing 2.16 ± 0.52 g, were stocked in 12 28-L tanks to test the following treatments: proactive (PT), reactive (RT) and mixed (MT) composed of reactive (MRT) and proactive (MPT) animals. In Phase 2 of the experiment (40 days of cultivation), the animals were transferred to 175-L tanks with the same treatments as Phase 1. The animals were fed twice a day with commercial diet during both phases. After Phase 1, MPT animals showed higher growth than MRT animals (P < 0.05), and higher weight gain and daily weight than PT animals (P < 0.05). After Phase 2, PT animals showed higher weight gain and daily weight gain than RT and MT animals (P < 0.05), as did MPT animals compared to PT animals. Performance for RT animals was superior (P < 0.05) to that of MRT animals. Glucose (P < 0.04) and cholesterol (P < 0.01) were higher for RT animals compared to PT animals. Cholesterol was higher for MPT animals compared to MRT animals (P < 0.01), while plasma protein was lower (P < 0.001). Glucose (P < 0.001) and cholesterol (P < 0.01) were higher for MPT animals compared to PT animals and for MRT animals compared to RT animals (glucose P < 0.02, cholesterol P < 0.01). After 90 days of cultivation, proactive animals cultivated separately presented better performance. When cultivated together, reactive animals experienced a decrease in performance and both stress coping styles showed more signs of stress.

Lysosomal cholesterol accumulation in aged astrocytes impairs cholesterol delivery to neurons and can be rescued by cannabinoids.

Cholesterol is crucial for the proper functioning of eukaryotic cells, especially neurons, which rely on cholesterol to maintain their complex structure and facilitate synaptic transmission. However, brain cells are isolated from peripheral cholesterol by the blood-brain barrier and mature neurons primarily uptake the cholesterol synthesized by astrocytes for proper function. This study aimed to investigate the effect of aging on cholesterol trafficking in astrocytes and its delivery to neurons. We found that aged astrocytes accumulated high levels of cholesterol in the lysosomal compartment, and this cholesterol buildup can be attributed to the simultaneous occurrence of two events: decreased levels of the ABCA1 transporter, which impairs ApoE-cholesterol export from astrocytes, and reduced expression of NPC1, which hinders cholesterol release from lysosomes. We show that these two events are accompanied by increased microR-33 in aged astrocytes, which targets ABCA1 and NPC1. In addition, we demonstrate that the microR-33 increase is triggered by oxidative stress, one of the hallmarks of aging. By coculture experiments, we show that cholesterol accumulation in astrocytes impairs the cholesterol delivery from astrocytes to neurons. Remarkably, we found that this altered transport of cholesterol could be alleviated through treatment with endocannabinoids as well as cannabidiol or CBD. Finally, according to data demonstrating that aged astrocytes develop an A1 phenotype, we found that cholesterol buildup is also observed in reactive C3+ astrocytes. Given that reduced neuronal cholesterol affects synaptic plasticity, the ability of cannabinoids to restore cholesterol transport from aged astrocytes to neurons holds significant implications in aging and inflammation.

Structural characterization of cholesterol-rich nanoemulsion (LDE).

Cholesterol-rich nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and can concentrate those agents in the neoplastic and inflammatory tissues. This method improves the biodistribution of the drug and reduces toxicity. However, the structural stability of LDE particles, without or with associated drugs, has not been extensively investigated. The aim of the present study is to investigate the structural stability of LDE and LDE associated to paclitaxel, etoposide or methotrexate in aqueous solution over time by small-angle X-ray scattering (SAXS and Ultra SAXS) and dynamic light scattering (DLS). The results show that LDE and LDE associated with those chemotherapeutic agents had reproducible and stable particle diameter, physical structure, and aggregation behavior over 3-month observation period. As estimated from both DLS and Ultra-SAXS methods, performed at pre-established intervals, the average particle diameter of LDE alone was approx. 32 nm, of LDE-paclitaxel was 31 nm, of LDE-methotrexate was 35 nm and of LDE-etoposide was 36 nm. Ultra-SAXS analysis showed that LDE nanoparticles were quasi-spherical, and SAXS showed that drug molecules inside the particles showed a layered-like organization. Formulations of LDE with associated PTX, ETO or MTX were successfully tested in animal experiments and in patients with cancer or with cardiovascular disease, showing markedly low toxicity, good tolerability and possible superior pharmacological action. Our results may be useful for ensuing clinical trials of this novel Nanomedicine tool, by strengthening the knowledge of the structural aspects of those LDE formulations.

Effects of physical training on the metabolic profile of rats exposed to chronic restraint stress.

INTRODUCTION: Despite strong evidences supporting the protective role of exercise against stress-induced repercussions, the literature remains inconclusive regarding metabolic aspects. Therefore, this study aimed to evaluate the effect of Physical Training (PT) by swimming on the metabolic parameters of rats subjected to restraint stress. METHODS: Wistar rats (n = 40) were divided into four groups: Control (C), Trained (T), Stressed (S), and Trained/Stressed (TS). The restraint stress protocol involved confining the animals in PVC pipes for 60 minutes/day for 12 weeks. Concurrently, the swimming PT protocol was performed without additional load in entailed sessions of 60 minutes conducted five days a week for the same duration. The following parameters were analyzed: fitness progression assessed by the physical capacity test, body mass, serum level of glucose, triglyceride, cholesterol and corticosterone, as well as glycemic tolerance test, evaluated after glucose administration (2 g/kg, i.p.). RESULTS: Trained groups (T and TS) exhibited enhanced physical capacity (169 ± 21 and 162 ± 22% increase, respectively) compared to untrained groups (C: 9 ± 5 and S: 11 ± 13% increase). Corticosterone levels were significantly higher in the S group (335 ± 9 nmoL/L) compared to C (141 ± 3 nmoL/L), T (174 ± 3 nmoL/L) and TS (231 ± 7 nmoL/L), which did not differ from each other. There were no significant changes in serum glucose, cholesterol, and triglyceride levels among the groups. However, the glycemic curve after glucose loading revealed increased glycemia in the S group (area under curve 913 ± 30 AU) but the TS group exhibited values (673 ± 12 AU) similar to the groups C (644 ± 10 AU) and T (649 ± 9 AU). CONCLUSION: Swimming-based training attenuated stress-induced corticosterone release and prevented glucose intolerance in rats, reinforcing the importance of exercise as a potential strategy to mitigate the pathophysiological effects of stress.

Comparison of the Friedewald and Vujovic methods with the calculated LDL concentration in a biochemical auto-analyzer.

Objective: To compare the concentration of Low-Density Lipoprotein (LDL-c) obtained using the Friedewald formula with those obtained directly with the RAYTO CHEMRAY 120 autoanalyzer. Methods: Cross-sectional study. We evaluated outpatients with a medical request for a lipid profile study (total cholesterol, triglycerides, LDL, and HDL). The analyses were carried out in a RAYTO CHEMRAY 120 autoanalyzer under the principle of spectrophotometry. We obtained LDL-c using the Friedewald and Vujovic formulas. Results: We evaluated 199 individuals whose direct LDL concentration averages were measured by the RAYTO CHEMRAY 120 equipment. Those calculated by the Friedewald and Vujovic formulas were 129.97 ± 32.66, 119.28 ± 30.44, and 127.01 ± 32.01, respectively, and in all cases, significant differences (P < 0.001) were observed with the RAYTO analyzer. In both cases a low positive bias was found with the RAYTO analyzer.. The Passing-Bablok and Deming's regressions showed a linear correlation between both methods (Friedewald and Vujovic) with the LDL values obtained with the Rayto autoanalyzer. Conclusions: Our study found that the Friedewald and Vujovic methods are good predictors of LDL cholesterol levels and have a low level of bias. Therefore, they could be used as potential predictors.

Objetivo: Comparar las concentraciones de Lipoproteínas de Baja Densidad (LDL-c) obtenidas mediante la fórmula de Friedewald con las obtenidas directamente con el autoanalizador RAYTO CHEMRAY 120. Métodos: Estudio transversal. Se evaluaron pacientes ambulatorios con solicitud médica de perfil lipídico (colesterol total, triglicéridos, LDL y HDL). Los análisis se realizaron con un autoanalizador RAYTO CHEMRAY 120 bajo el principio de espectrofotometría. Obtuvimos el LDL-c usando las fórmulas de Friedewald y Vujovic. Resultados: Se evaluaron 199 individuos cuyos promedios directos de concentración de LDL fueron medidos con el equipo RAYTO CHEMRAY 120. Las concentraciones calculadas por las fórmulas de Friedewald y Vujovic fueron de 129,97 ± 32,66, 119,28 ± 30,44, y de 127,01 ± 32,01, respectivamente, y en todos los casos se observaron diferencias significativas (P < 0,001) con el analizador RAYTO. En ambos casos se encontró un sesgo positivo bajo en el analizador RAYTO. Las regresiones de Passing-Bablok y Deming mostraron una correlación lineal entre ambos métodos (Friedewald y Vujovic) con los valores de LDL obtenidos con el autoanalizador Rayto. Conclusión: Nuestro estudio encontro que los métodos de Friedewald y Vujovic son buenos predictores de los niveles de colesterol LDL y presentan un nivel de sesgo bajo. Por lo que podrían usarse como potenciales predictores.

Consumption of a Byproduct of Chia Seed Oil Extraction by Cold Pressing Ameliorates Cardiovascular Risks Factors in an Experimental Model of Metabolically Unhealthy Normal Weight.

The byproduct of Salvia hispanica (chia) seed oil extraction by cold pressing, also known as expeller, possesses a high nutritional value. It is rich in proteins, fibers, minerals, and has a residual oil content of 7-11%, which is rich in omega 3 linolenic acid (ALA). However, this byproduct has been historically undervalued. Thus, the aim of current work was to study the effects of consuming of a rich in chia expeller diet on a rabbit model of metabolically unhealthy normal weight to validate their use as a functional food. Rabbits were fed different diets for a period of 6 weeks: a standard diet (CD), a high-fat diet (HFD), a rich in expeller CD (Exp-CD) and a rich in expeller HFD (Exp-HFD). The Exp-HFD attenuated the rise in basal glucose, TyG index, triglycerides, cholesterol and non-HDL cholesterol induced by the HFD. Both rich in expeller diets reduced mean arterial blood pressure (MAP) and increase liver and fat ALA levels compared to their respective controls. Furthermore, the angiotensin converting enzyme (ACE) activity was lower in the lungs of animals fed on rich in expeller diets compared to their respective controls. In vitro studies showed that ALA inhibited ACE activity. The evaluation of vascular reactivity revealed that rich in expeller diets improved angiotensin II affinity and reduced contractile response to noradrenaline. In conclusion, the consumption of rich in expeller diets showed beneficial effects in preventing cardiovascular risk factors such as insulin resistance, dyslipidemia and MAP. Therefore, its use as functional ingredient holds significant promise.

Development of Liposomes Loaded with Chloroaluminum Phthalocyanine for Application of Photodynamic Therapy in Breast Cancer.

Chloraluminium phthalocyanine (ClAlPc) has potential therapeutic effect for the treatment of cancer; however, the molecule is lipophilic and may present self-aggregation which limits its clinical success. Thus, nanocarriers like liposomes can improve ClAlPc solubility, reduce off-site toxicity and increase circulation time. For this purpose, developing suitable liposomes requires the evaluation of different lipid compositions. Herein, we aimed to develop liposomes containing soy phosphatidylcholine (SPC), 1,2-distearoyl-sn-glycero- 3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPEPEG2000), cholesterol and oleic acid loaded with ClAlPc using the surface response methodology and the Box-Behnken design. Liposomes with particle size from 110.93 to 374.97 nm and PdI from 0.265 to 0.468 were obtained. The optimized formulation resulted in 69.09 % of ClAlPc encapsulated, with particle size and polydispersity index, respectively, at 153.20 nm and 0.309, providing stability and aggregation control. Atomic force microscopy revealed vesicles in a spherical or almost spherical shape, while the analyzes by Differential Scanning Calorimetry (DSC), Powder X-ray Diffraction (PXRD), and Fourier transform infrared spectroscopy (FTIR) suggested that the drug was adequately incorporated into the lipid bilayer of liposomes, in its amorphous state or molecularly dispersed. In vitro studies conducted in breast cancer cells (4T1) showed that liposome improved phototoxicity compared to the ClAlPc solution. ClAlPc-loaded liposomes also enhanced the production of ROS 3-fold compared to the ClAlPc solution. Finally, confocal microscopy and flow cytometry demonstrated the ability of the liposomes to enter cells and deliver the fluorescent ClAlPc photosensitizer with dose and time-dependent effects. Thus, this work showed that Box-Behnken factorial design was an effective strategy for optimizing formulation development. The obtained ClAlPc liposomes can be applied for photodynamic therapy in breast cancer cells.

Insulin resistance potentiates the effect of remnant cholesterol on cardiovascular mortality in individuals without diabetes.

BACKGROUND AND AIMS: Remnant cholesterol (RC) and insulin resistance (IR) have been independently associated with cardiovascular risk. Here, we evaluated the role of IR and RC on cardiovascular disease (CVD) mortality. METHODS: We conducted an analysis of 16,113 individuals ≥20 years without diabetes from the National Health and Nutrition Examination Survey (NHANES-III/IV). RC levels were calculated using total cholesterol, non-HDL-c, and LDL-c; IR was defined as HOMA2-IR≥2.5 and CVD mortality as a composite of cardiovascular and cerebrovascular mortality. Multiple linear regression was used to assess the relationship between HOMA2-IR and RC and Cox regression models to assess their joint role in CVD mortality. Causally ordered mediation models were used to explore the mediating role of IR in RC-associated CVD mortality. RESULTS: We identified an association between higher HOMA2-IR and higher RC levels. The effect of IR on CVD mortality was predominant (HR 1.32, 95%CI 1.18-1.48) and decreased at older ages (HR 0.934, 95%CI 0.918-0.959) compared to RC (HR 0.983, 95%CI 0.952-1.014). Higher risk of CVD mortality was observed in individuals with IR but normal RC (HR 1.37, 95%CI 1.25-1.50) and subjects with IR and high RC (HR 1.24, 95%CI 1.13-1.37), but not in subjects without IR but high RC. In mediation models, HOMA2-IR accounted for 78.2% (95%CI 28.11-98.89) of the effect of RC levels on CVD mortality. CONCLUSIONS: Our findings suggest that RC potentiates the risk of CVD mortality through its effect on whole-body insulin sensitivity, particularly among younger individuals.

Asociación entre los marcadores lipídicos en la infancia/ adolescencia y los eventos cardiovasculares en la adultez: una revisión sistemática / Association between lipid markers in childhood/ adolescence and cardiovascular events in adulthood: A systematic review

Introducción. La asociación entre los marcadores lipídicos en la infancia/adolescencia y la incidencia de eventos clínicos cardiovasculares en la adultez está poco explorada en la literatura. El objetivo de esta revisión sistemática fue analizar la evidencia disponible sobre este tema. Población y métodos. Esta revisión sistemática se realizó de acuerdo con las guías PRISMA. Se realizó una búsqueda bibliográfica para detectar los estudios que evaluaron la asociación entre los niveles lipídicos en la edad pediátrica y la incidencia de eventos cardiovasculares en la edad adulta. No hubo restricciones idiomáticas ni geográficas en la búsqueda. Resultados. En total, cinco estudios observacionales (todas cohortes prospectivas) que incluyeron 43 540 pacientes fueron identificados y considerados elegibles para este estudio. Cuatro estudios evaluaron el nivel de triglicéridos; todos reportaron una asociación significativa entre este marcador en la edad pediátrica y los eventos cardiovasculares en la adultez. Un estudio reportó la misma asociación con el nivel de colesterol total, mientras que otro evidenció el valor predictivo de la lipoproteína (a) para el mismo desenlace clínico. Un solo estudio evaluó el colesterol asociado a lipoproteínas de alta densidad (C-HDL), sin encontrar una relación con el punto final de interés. El análisis del colesterol asociado a lipoproteínas de baja densidad (C-LDL) arrojó resultados contradictorios, aunque la asociación fue significativa en los estudios con un tamaño muestral más grande y con un mayor número de eventos durante el seguimiento. Conclusión. Los datos de esta revisión sugieren que las alteraciones de los marcadores lipídicos en la infancia y la adolescencia se asocian con un mayor riesgo cardiovascular en la adultez temprana y media.

Introduction. The association between lipid markers in childhood/adolescence and the incidence of clinical cardiovascular events in adulthood has been little explored in the bibliography. The objective of this systematic review was to analyze available evidence on this topic. Population and methods. This systematic review was conducted in accordance with the PRISMA guidelines. A comprehensive bibliographic search was done to find studies assessing the association between lipid levels in childhood and the incidence of cardiovascular events in adulthood. There were no language or geographic restrictions. Results. A total of 5 observational studies (all prospective cohorts) including 43 540 patients were identified and considered eligible for this study. Four studies assessed triglyceride levels; all reported a significant association between this lipid marker in childhood and cardiovascular events in adulthood. A study reported the same association with total cholesterol level, while another showed the predictive value of lipoprotein (a) for the same clinical outcome. Only one study assessed high-density lipoprotein cholesterol (HDL-C), but it did not find an association with the endpoint of interest. The analysis of lowdensity lipoprotein cholesterol (LDL-C) showed contradictory results, although the association was significant in the studies with a larger sample size and a higher number of events during follow-up. Conclusion. According to this review, alterations in lipid markers in childhood and adolescence are associated with a higher cardiovascular risk in early and middle adulthood.

Effects of high-intensity interval training and its different protocols on lipid profile and glycaemic control in type 2 diabetes: A meta-analysis.

This meta-analysis of randomised clinical trials aimed to compare the effects of high-intensity interval training (HIIT) and its different protocols versus moderate-intensity continuous training (MICT) and/or control on total cholesterol, HDL, LDL, triglycerides, HbA1c levels, and fasting glucose in individuals with type 2 diabetes mellitus (T2DM). The search strategy was performed in PubMed/MEDLINE, Cochrane CENTRAL, EMBASE, Web of Science, Sport DISCUS, and PEDro, until January 2023. A total of 31 studies (1092 individuals) were included. When compared to control, HIIT decreased total cholesterol by -0.31 mmol/L (95% CI -0.49; -0.12), LDL by -0.31 mmol/L (95% CI -0.49; -0.12), triglycerides by -0.27 mmol/L (95% CI -0.33; -0.2), HbA1c by -0.75% (95% CI -0.97; -0.53), fasting glucose by -1.15 mmol/L (95% CI -1.44; -0.86), and increased HDL by 0.24 mmol/L (95% CI 0.06; 0.42). No difference was found in the comparison between HIIT versus MICT for any of the outcomes analysed, however subgroup analysis showed that a moderate-interval (>30s to < 2 min) and moderate-term (>4 to < 12 weeks) HIIT protocol reduced total cholesterol, when compared to MICT. HIIT is able to improve lipid profile and glycaemic control in T2DM individuals, and specific protocols can be recommended for improving total cholesterol levels.

Cholesterol depletion induces mesenchymal properties in oral squamous cell carcinoma cell line.

BACKGROUND: Cholesterol in cell membranes is crucial for cell signaling, adhesion, and migration. Membranes feature cholesterol-rich caveolae with caveolin proteins, playing roles in epithelial-mesenchymal transition and cancer progression. Despite elevated cholesterol levels in tumors, its precise function and the effects of its depletion in oral squamous cell carcinoma remain unclear. The aim of this study was to evaluate the influence of cholesterol depletion in oral squamous cell carcinoma cell line and epithelial-mesenchymal transition process. METHODS: Cholesterol depletion was induced on SCC-9 cells by methyl-ß-cyclodextrin and cell viability, proliferation, apoptosis, and colony formation capacities were evaluated. Gene and protein expressions were evaluated by reverse transcription polymerase chain reaction (RT-qPCR) and Western Blot, respectively, and cell sublocalization was assessed by immunofluorescence. RESULTS: Cholesterol depletion resulted in alteration of oral squamous cell carcinoma cell morphology at different concentrations of methyl-ß-cyclodextrin, as well as decreased cell proliferation and viability rates. Analysis of CAV1 transcript expression revealed increased gene expression in the treated SCC-9 during the 24 h period, at different concentrations of methyl-ß-cyclodextrin: 5 , 7.5, 10, and 15 mM, in relation to parental SCC-9. CAV1 protein expression was increased, with subsequent dose-dependent decrease. A statistically significant difference was observed in samples treated with 5 mM of methyl-ß-cyclodextrin (p = 0.02, Kruskal-Wallis test). The immunofluorescence assay showed lower cytoplasmic and membrane labeling intensity in the treated samples for CAV1. CONCLUSION: These findings indicate the modulation of cholesterol as a possible mechanism underlying the regulation of these molecules and activation of epithelial-mesenchymal transition in oral squamous cell carcinoma.