Lipids are the most abundant biomolecules of human plasma, and their balance plays a significant role in health and disease management. Despite the importance of lipids, the studies focused on the comprehensive determina...Lipids are the most abundant biomolecules of human plasma, and their balance plays a significant role in health and disease management. Despite the importance of lipids, the studies focused on the comprehensive determination of the plasma lipidome in children are limited. In this study, we investigated the sex, age, and weight-specific changes in the plasma lipidome of nonfasting preadolescent children aged 9-12 years ( = 342) using a nontargeted liquid chromatography-mass spectrometry technique. A total of 219 lipid species were characterized in the plasma samples. Multivariate analysis revealed that boys and girls have similar lipid profiles, but relatively higher levels of capric acid-composed triacylglycerols (TGs) were observed in plasma samples of boys. Saturated fatty acids are the most abundant fatty acyls followed by mono- and polyunsaturated fatty acids in the plasma of both boys and girls. Sphingolipids such as ceramides, hexosylceramides, sphingomyelin, and a phospholipid (phosphatidylinositol) were relatively higher in the plasma of a 10-year-old group than other age groups. Plasma levels of TG and phosphatidylserine were increased within age from 9 to 12 years. Furthermore, most of the TG molecular species were increased in the plasma of overweight children compared to the normal range groups. The receiver operating characteristic analysis results show that TG (10:0/10:0/18:1) could be a specific marker for childhood obesity (area under the curve (AUC) = 0.72). Overall, this study highlights the altered plasma lipidome in preadolescent children for sex, age, and percentage of overweight. Early detection of lipid markers for obesity would be a promising target for developing therapeutic strategies.
Paternal exposure to high-fat diets or individual fatty acids (FAs) including arachidonic acid (AA) modifies progeny traits by poorly understood mechanisms. Specific male reproductive system FAs may be involved in patern...Paternal exposure to high-fat diets or individual fatty acids (FAs) including arachidonic acid (AA) modifies progeny traits by poorly understood mechanisms. Specific male reproductive system FAs may be involved in paternal inheritance, as they can modify a range of cellular components, including the epigenome. Our objective was to determine FAs in compartments of the male reproductive system that potentially affect ejaculate composition-right and left testicular interstitial fluid (TIF), vesicular gland fluid (VGF), and epididymal adipose tissue (EAT)-in mice exposed to AA or vehicle daily for 10 days ( = 9-10/group). Whole blood (WB) and interscapular brown adipose tissue (IBAT) FA profiles were used as reference. AA significantly affected only VGF FAs relative to vehicle, that is, increased and decreased levels of arachidic and docosahexaenoic acid, respectively, versus vehicle (0.28% ± 0.01% and 0.23% ± 0.03%, respectively, = 0.049, and 2.42% ± 0.47% and 3.00% ± 0.58%, respectively, = 0.041). AA affected distinct FAs in WB. Additionally, we uncovered AA-dependent and AA-independent FA laterality. Myristic acid was higher in AA-exposed left versus right TIF (0.68% ± 0.35% and 0.60% ± 0.11%, respectively, = 0.004). Right TIF contained higher oleic and linoleic acid and lower stearic acid than left TIF (29.01% ± 3.07% and 24.00% ± 2.18%, respectively, = 0.005; 9.14% ± 1.88% and 7.05% ± 1.36%, respectively, = 0.005; and 21.90% ± 2.92% and 26.01% ± 2.46%, respectively, = 0.036), irrespective of exposure to AA. The TIF oleic/stearic acid ratio suggested higher Stearoyl-CoA Desaturase 1 activity in the right versus the left testis (1.35 ± 0.32 and 1.00 ± 0.17, respectively, = 1.0 × 10). Multitissue comparisons revealed that TIF and VGF FA profiles were distinct from WB, EAT, or IBAT counterparts, suggesting tissue-specific FA fingerprints. In conclusion, AA modulated selected VGF long-chain FAs that may impact on uterine inflammation and subsequent embryonic development. AA altered local FA synthesis or selective uptake, rather than eliciting passive uptake from WB. Additionally, we uncover a significant laterality of testis FAs that may result in asymmetric sperm cell phenotypes.
G1, a specific agonist targeting the G protein-coupled receptor 30 (GPR30), has demonstrated significant involvement in combating obesity and regulating glucose homeostasis. Nevertheless, the beneficial effects of G1 tre...G1, a specific agonist targeting the G protein-coupled receptor 30 (GPR30), has demonstrated significant involvement in combating obesity and regulating glucose homeostasis. Nevertheless, the beneficial effects of G1 treatment have solely been investigated in animal models under normal feeding conditions, leaving its therapeutic potential in high-fat feeding scenarios unexplored. To address this gap, our study employed an ovariectomized high-fat diet mouse model to assess the therapeutic effects of G1 in combating obesity and metabolic dysfunction. The findings revealed that G1 treatment resulted in weight loss, but concurrently led to increased blood glucose levels and insulin resistance. Treatment with G1 resulted in an amplification of fat mobilization and an enhancement of pyruvate carboxylase activity in mice fed a high-fat diet. Moreover, the combined impact of G1 treatment and a high-fat diet on pyruvate metabolism, as well as the regulation of crucial gluconeogenesis enzymes such as pyruvate dehydrogenase kinase 4 (PDK4), phosphoenolpyruvate carboxykinase (PEPCK), and glucose transporter 2 (GLUT2), expedites the elevation of blood glucose and the progression of insulin resistance. These findings indicate that G1 treatment is influenced by a high-fat diet, potentially disrupting glucolipid metabolism and promoting insulin resistance alongside its antiobesity effects. Consequently, further investigation is imperative to thoroughly explore this potential toxic side effect of G1 therapy.
The study examined Soler. (family LOGANIACEAE) fruit as a potential source of vegetable oil. Ripe fruits collected from a forested site in Zimbabwe were processed to determine the partitioning of fresh and dry fruit bio...The study examined Soler. (family LOGANIACEAE) fruit as a potential source of vegetable oil. Ripe fruits collected from a forested site in Zimbabwe were processed to determine the partitioning of fresh and dry fruit biomass. The oil was extracted from the seed coat using a hand-operated screw press, and its physiological properties were analyzed. Seeds contributed the most to the fresh weight of the fruit, followed by the shell and pulp. The seed coat was a significant component of the seeds. The seed coat, but not the pulp of the fruit, was found to contain screw press-extractable oil, the yield of which was substantial, amounting to around 39% of the dry weight of the seed coat. The oil was found to have a high free fatty acid content and a moderate iodine value (83 gI/100 g), indicating a degree of unsaturation. Furthermore, the oil contained carotenoids and tocols, which serve as antioxidants that help to protect the oil from oxidation. The oil had a high content of monounsaturated oleic acid (78.3%), which is known for its stability and health benefits. The low levels of saturated and polyunsaturated fatty acids make it a high oleic oil. The volatile profile of the oil included compounds with pleasant fruity aromas that enhance its flavour and fragrance. The results highlighted the need for waste management strategies if is industrialized as an oil crop. Significant waste, including shells, pulp, cake residue, and seed kernels, would need proper handling and valorisation. In summary, the research showed that has the potential to be a valuable source of high-quality vegetable oil with good oxidative stability and health benefits, primarily due to its high content of oleic acid and antioxidant compounds.
Triterpenoids have been identified as potential novel lipid-lowering drugs for the treatment of hypertriglyceridemia. This study investigated the potential antilipogenic and/or antilipolytic effects of two triterpenoids...Triterpenoids have been identified as potential novel lipid-lowering drugs for the treatment of hypertriglyceridemia. This study investigated the potential antilipogenic and/or antilipolytic effects of two triterpenoids (ARM-2 and RA-5) isolated from the stem bark of (Benrh.) Engl. Employing a combination of in silico predictions and in vitro assays, the interactions between these triterpenoids and key proteins involved in lipogenesis and lipolysis were investigated. In silico molecular docking analysis predicted a favourable binding affinity of both triterpenoids to PPAR, SREBP-1, and AMPK, with lower binding affinity to C/EBP, pancreatic lipase, and hormone-sensitive lipase (HSL). Both triterpenoids exhibited in vitro inhibition of pancreatic lipase with K and IC values ranging from 28.7 to 52.9 M and 27.6 to 35.8 M, respectively. Total and neutral lipid accumulation in differentiated 3T3-L1 adipocytes and the oleic acid-induced HepG2 cell model was inhibited, with ARM-2 showing better inhibition than RA-5. In the HepG2 model, the inhibitory activity of the two triterpenoids (at 25 and 100 M) was comparable to 50 M lovastatin, although the latter was cytotoxic, whereas both ARM-2 and RA-2 lacked cytotoxicity. Associated gene expression was similar to the effect of simvastatin where the expression of SREBP-1, PPAR, C/EBP, and HSL was reduced and that of AMPK was unchanged. In vitro studies confirmed that ARM-2 and RA-5 also inhibited adipocyte lipolysis, where the reduction in glycerol release by 25 and 100 M was similar to 50 M lovastatin and simvastatin. This study identifies that the triterpenoids, ARM-2 and RA-5, have the potential to modulate lipogenesis and lipolysis.
Identifying -cells dysregulation in type 2 diabetes mellitus (T2DM) is crucial. Weight fluctuations are frequently observed during diabetes treatment. However, the relationship between body composition changes and islet...Identifying -cells dysregulation in type 2 diabetes mellitus (T2DM) is crucial. Weight fluctuations are frequently observed during diabetes treatment. However, the relationship between body composition changes and islet -cell function in individuals with T2DM remains insufficiently investigated. This retrospective longitudinal study encompassed a cohort of 775 T2DM patients, who underwent body composition measuring using dual-energy X-ray absorptiometry (DEXA) and followed up for a median of 2.29 years. Key metrics included body mass index (BMI), fat mass index (FMI), trunk fat mass index (TFMI), muscle mass index (MMI), appendicular skeletal muscle mass index (ASMI), muscle/fat mass ratio (M/F), and the appendicular skeletal muscle mass/trunk fat mass ratio (A/T) were then categorized and grouped. Insulin, C-peptide, and glucose levels were assessed concurrently following a glucose load. -cell function included insulin resistance (HOMA-IR), insulin sensitivity (Matsuda index (MI)), and insulin secretion evaluated by HOMA- and C-peptidogenic index (CGI). Although no significant changes in BMI were observed, patients with T2DM at readmission exhibited higher FMI, TFMI, and ASMI, as well as elevated levels of HOMA-IR, MI, and CGI compared to baseline measurements. And lower MI, higher levels of CGI, and HOMA-IR were observed in BMI increased group. Univariate correlation analysis revealed a negative association between changes in BMI (BMI) and MI, while positive associations were observed in both HOMA-IR and CGI. Among body composition indexes, FMI exhibited the strongest correlation with HOMA-IR ( = 0.255, < 0.001), and ASMI was positively associated with MI and CGI ( = 0.131 and 0.194, respectively). Moreover, increased levels of BMI and FMI were associated with a greater risk of progressive insulin resistance compared to the decreased, whereas the trend was converse in ASMI and A/T. Increased FMI may partially contribute to the deterioration of insulin resistance, while increased ASMI is associated with improved insulin sensitivity and secretion. Maintaining an appropriate BMI and muscle/fat ratio is conductive to prevent the progression of insulin resistance in patients with T2DM.
Adipose tissue is mainly composed by adipocytes. Moreover, mesenchymal stromal/stem cells (MSCs), macrophages, endothelial cells, and extracellular matrix components are present. The variety of molecules as cytokines and...Adipose tissue is mainly composed by adipocytes. Moreover, mesenchymal stromal/stem cells (MSCs), macrophages, endothelial cells, and extracellular matrix components are present. The variety of molecules as cytokines and growth factors of its structure very rich in blood vessel makes it also similar to a true endocrine organ that however needs still to be fully investigated. In our study, we used human lipoaspirate to obtain mechanically microfragmented fat (MiFAT) which was washed and then devitalized by freezing-thawing cycles. In our experiments, thawed MiFAT was used to stimulate cultures of MSCs from two different sources (adipose tissue and gingiva papilla) in comparison with a traditional stimulation in vitro obtained by culturing MSCs with adipogenic medium. MSCs stimulated with MiFAT showed a very early production of lipid droplets, after only 3 days, that correlated with an increased expression of adipokines. Furthermore, a significant upregulation of PPAR gamma 1 alpha coactivator (PPARGC1A) was observed with an overexpression of uncoupling protein 1 (UCP1) that suggest a pattern of differentiation compatible with the beige-brown fat.
Topical drug delivery employing drug nanocarriers has shown prominent results in treating topical ailments, especially those confined to the skin and eyes. Conventional topical formulations persist with drug and disease-...Topical drug delivery employing drug nanocarriers has shown prominent results in treating topical ailments, especially those confined to the skin and eyes. Conventional topical formulations persist with drug and disease-related challenges during treatment. Various nanotechnology-driven approaches have been adopted to mitigate the issues associated with conventional formulations. Among these, cubosomes have shown potential applications owing to their liquid crystalline structure, which aids in bioadhesion, retention, sustained release, and loading hydrophilic and hydrophobic moieties. The phase transition behavior of glyceryl monooleate, the concentration of stabilizers, and critical packing parameters are crucial parameters that affect the formation of cubosomes. Microfluidics-based approaches constitute a recent advance in technologies for generating stable cubosomes. This review covers the recent topical applications of cubosomes for treating skin (psoriasis, skin cancer, cutaneous candidiasis, acne, and alopecia) and eye (fungal keratitis, glaucoma, conjunctivitis, and uveitis) diseases. The article summarizes the manufacturing and biological challenges (skin and ocular barriers) that must be considered and encountered for successful clinical outcomes. The patented products are successful examples of technological advancements within cosmeceuticals that support various topical applications with cubosomes in the pharmaceutical field.
Thyroid hormone (TH) is essential for maintaining normal physiological processes during pregnancy, including the metabolism of energy materials in both the mother and fetus and the growth and development of fetal bone an...Thyroid hormone (TH) is essential for maintaining normal physiological processes during pregnancy, including the metabolism of energy materials in both the mother and fetus and the growth and development of fetal bone and nervous system. TH can act on the liver, fat, and other tissues and organs to participate in lipid synthesis and breakdown through multiple pathways. Consequently, abnormal thyroid function is often accompanied by lipid metabolism disorders. Both clinical and subclinical hypothyroidism, as well as dyslipidemia during pregnancy, have been shown to be associated with an increased risk of multiple adverse pregnancy outcomes. Recently, there has been an increased interest in studying the alteration of lipidomic and hypothyroidism (both clinical and subclinical hypothyroidism) during pregnancy. Studies have suggested that altered lipid molecules might be used as potential biomarker and associated with adverse maternal and neonatal outcome. Thus, we summarized the associations between lipid metabolism and clinical or subclinical hypothyroidism during pregnancy in this review. Then, we discussed the underlying mechanisms of thyroid dysfunction and lipid metabolism. In addition, we reviewed the possible effect of dyslipidemia on pregnancy and neonatal outcome. However, the relationship between hypothyroidism during pregnancy and changes in the lipid profile and how to intervene in the occurrence and development of adverse pregnancy outcomes require further study.
BACKGROUND: Diabetic retinopathy (DR) is a diabetic microvascular complication and a leading cause of vision loss. However, there is a lack of effective strategies to reduce the risk of DR currently. The present study is...BACKGROUND: Diabetic retinopathy (DR) is a diabetic microvascular complication and a leading cause of vision loss. However, there is a lack of effective strategies to reduce the risk of DR currently. The present study is aimed at assessing the causal effect of lipid-regulating targets on DR risk using a two-sample Mendelian randomization (MR) study. METHOD: Genetic variants within or near drug target genes, including eight lipid-regulating targets for LDL-C (HMGCR, PCSK9, and NPC1L1), HDL-C (CETP, SCARB1, and PPARG), and TG (PPARA and LPL), were selected as exposures. The exposure data were obtained from the IEU OpenGWAS project. The outcome dataset related to DR was obtained from the FinnGen research project. Inverse-variance-weighted MR (IVW-MR) was used to calculate the effect estimates by each target. Sensitivity analyses were performed to verify the robustness of the results. RESULTS: There was suggestive evidence that PCSK9-mediated LDL-C levels were positively associated with DR, with OR (95% CI) of 1.34 (1.02-1.77). No significant association was found between the expression of HMGCR- and NPC1L1-mediated LDL-C levels; CETP-, SCARB1-, and PPARG-mediated HDL-C levels; PPARA- and LPL-mediated TG levels; and DR risk. CONCLUSIONS: This is the first study to reveal a genetically causal relationship between lipid-regulating drug targets and DR risk. PCSK9-mediated LDL-C levels maybe positively associated with DR risk at the genetic level. This study provides suggestive evidence that PCSK9 inhibition may reduce the risk of DR.
Gangliosides, sialic acid-containing glycosphingolipids, are abundant in cell membranes and primarily involved in controlling cell signaling and cell communication. The altered ganglioside pattern has been demonstrated i...Gangliosides, sialic acid-containing glycosphingolipids, are abundant in cell membranes and primarily involved in controlling cell signaling and cell communication. The altered ganglioside pattern has been demonstrated in several neurodegenerative diseases, characterized during early-onset or infancy, emphasizing the significance of gangliosides in the brain. Enzymes required for the biosynthesis of gangliosides are linked to several devastating neurological disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), hereditary spastic paraplegia (HSP). In this review, we summarized not only the critical roles of biosynthetic enzymes and their inhibitors in ganglioside metabolism but also the efficacy of treatment strategies of ganglioside to address their significance in those diseases.
BACKGROUND: Advanced lung cancer that contributes to a heavy burden on medical institutions is the leading cause of cancer-related death and is often accompanied by metabolic disorders. In this study, we aimed to explore...BACKGROUND: Advanced lung cancer that contributes to a heavy burden on medical institutions is the leading cause of cancer-related death and is often accompanied by metabolic disorders. In this study, we aimed to explore the biomarkers of diagnosis and radiotherapy response in non-small-cell lung cancer (NSCLC) patients by plasma lipidomics analysis. METHOD: Using triple-quadrupole mass spectrometer analysis, our research characterized the plasma lipid metabolomics profile of 25 healthy controls and 31 advanced NSCLC patients in each of three different radiotherapy phases. RESULTS: The results showed altered lipid elements and concentrations among NSCLC patients with different radiotherapy phases, NSCLC subtypes, and different radiotherapeutic responses. We found that compared to the healthy controls, myelin-associated glycoprotein (MAG), phosphatidylinositol (PI), and phosphatidylserine (PS) were mainly and significantly altered lipid elements (> twofold, and < 0.05) among NSCLC patients with different radiotherapy phases. Through comparison of lipid elements between bad and good responses of NSCLC patients with radiotherapy, the obviously declined phosphatidylglycerol (PG 18 : 0/14 : 0, 18 : 1/18 : 3, and 18 : 0/20 : 1) or markedly elevated PI (20 : 0/22 : 5 and 18 : 2/22 : 4) and phosphatidic acid (PA 14 : 0/20 : 4, 14 : 0/20 : 3, and 18 : 2/22 : 4) could indicate poor therapeutic response for NSCLC patients. The results of ROC curve analysis suggested that PG (18 : 0/20 : 1 and 18 : 0/14 : 0) could clearly predict the radiotherapeutic response for NSCLC patients, and PS (18 : 0/20 : 0) and cholesterol were the first two lipid components with the most potential for the diagnosis of advanced NSCLC. CONCLUSION: Our results indicated that plasma lipidomics profiling might have a vital value to uncover the heterogeneity of lipid metabolism in healthy people and advanced NSCLC patients with different radiotherapy phase, and further to screen out radiotherapeutic response-specific biomarkers.
BACKGROUND: Dyslipidemia, an abnormally high level of lipids in the blood, has a negative impact on the health status of the individual and has lately emerged as a major public health concern, especially for low- and mid...BACKGROUND: Dyslipidemia, an abnormally high level of lipids in the blood, has a negative impact on the health status of the individual and has lately emerged as a major public health concern, especially for low- and middle-income countries (LMIC) globally, including Ghana. However, it is still unclear what the burden and drivers of these lipid abnormalities are, especially among lactating women in the Upper West of Ghana. Thus, this study is aimed at determining the prevalence of dyslipidemia and its associated factors among lactating mothers in the Wa Municipality of Ghana. . A cross-sectional study was conducted from May to June 2020 in 8 health facilities within the Wa Municipality. Multistage and simple random sampling methods were used to select the facilities and the 200 study subjects. Sociodemographic data were collected using questionnaires, while blood samples were taken to determine the lipid profile of participants. Dietary patterns were also assessed using the Food Frequency Questionnaire (FFQ). Data were processed and analyzed using SPSS 17 software (SPSS, Inc., Chicago, IL). The chi-square test and multiple regression analysis were performed to determine the predictors associated with the various types of dyslipidemia, with statistical significance set at a value < 0.05. RESULTS: The prevalence of hypercholesterolemia (LDL-C), hypo-HDL-cholesterolemia, and hypertriglyceridemia (TG) was 57%, 59%, and 22%, respectively. Chi-square and multinomial regression analysis revealed that duration of lactation ( = 3.95, = 0.047), religion (AOR = 0.375, 95% CI 0.144-0.978, = 0.045), low income (AOR = 0.116, 95% CI 0.026-0.514, = 0.005), middle income (AOR = 0.163, 95% CI 0.044-0.600, = 0.006), and alcohol intake (AOR = 6.312, 95% CI 1.108-35.949, = 0.038) were associated with LDL-C, while age (AOR = 0.963, 95% CI 0.910-1.019, < 0.001) and educational status (AOR = 0.365, 95% CI 0.140-0.954, = 0.040) predicted HDL status. CONCLUSION: Dyslipidemia is common among lactating mothers of Wa Municipality, and it is predicted by lifestyle factors. Furthermore, future research to look at a larger sample size on dyslipidemia during lactation is recommended.
Recent evidence suggests that the majority of cholesterol-laden cells found in atherosclerotic lesions are vascular smooth muscle cells (VSMC) that have transdifferentiated into macrophage-like cells (MLC). Furthermore,...Recent evidence suggests that the majority of cholesterol-laden cells found in atherosclerotic lesions are vascular smooth muscle cells (VSMC) that have transdifferentiated into macrophage-like cells (MLC). Furthermore, cholesterol-laden MLC of VSMC origin have demonstrated impaired ABCA1-dependent cholesterol efflux, but it is poorly understood why this occurs. A possible mechanism which may at least partially be attributed to cholesterol-laden MLC demonstrating attenuated ABCA1-dependent cholesterol efflux is a miR-33a expression, as a primary function of this microRNA is to silence ABCA1 expression, but this has yet to be rigorously investigated. Therefore, the VSMC line MOVAS cells were used to generate miR-33a knockout (KO) MOVAS cells, and we used KO and wild-type (WT) MOVAS cells to delineate any possible proatherogenic role of miR-33a expression in VSMC. When WT and KO MOVAS cells were cholesterol-loaded to convert into MLC, this resulted in the WT MOVAS cells to exhibit impaired ABCA1-dependent cholesterol efflux. In the cholesterol-loaded WT MOVAS MLC, we also observed a delayed restoration of the VSMC phenotype when these cells were exposed to the ABCA1 cholesterol acceptor, apoAI. These results imply that miR-33a expression in VSMC drives atherosclerosis by triggering MLC transdifferentiation via attenuated ABCA1-dependent cholesterol efflux.
Phospholipids are asymmetrically distributed across mammalian plasma membrane. The function of P4-ATPases is to maintain the abundance of phosphatidylserine (PS) and phosphatidylethanolamine (PE) in the inner leaflet as...Phospholipids are asymmetrically distributed across mammalian plasma membrane. The function of P4-ATPases is to maintain the abundance of phosphatidylserine (PS) and phosphatidylethanolamine (PE) in the inner leaflet as lipid flippases. Transmembrane protein 30A (TMEM30A, also named CDC50A), as an essential subunit of most P4-ATPases, facilitates their transport and functions. With TMEM30A knockout mice or cell lines, it is found that the loss of TMEM30A has huge influences on the survival of mice and cells because of PS exposure-triggered apoptosis signaling. TMEM30A is a promising target for drug discovery due to its significant roles in various systems and diseases. In this review, we summarize the functions of TMEM30A in different systems, present current understanding of the protein structures and mechanisms of TMEM30A-P4-ATPase complexes, and discuss how these fundamental aspects of TMEM30A may be applied to disease treatment.
Cardiovascular disease causes significant personal, financial, and societal burden and is a major cause of mortality and morbidity globally. Dyslipidemia has proven to be a major factor that contributes to its increased...Cardiovascular disease causes significant personal, financial, and societal burden and is a major cause of mortality and morbidity globally. Dyslipidemia has proven to be a major factor that contributes to its increased incidence; thus, since a long time, low-density lipoprotein cholesterol-lowering therapies have been employed to reduce coronary artery disease-associated mortality. The first-line therapy for hyperlipidemia and dyslipidemia is statins. Evidence showed that statins decrease the level of LDL-C resulting in a lower risk of CVD (20-25% for every decrease of 1 mmol/L). However, due to statin intolerance in some patients and despite using maximal doses, they have not been successful in lowering cardiovascular-associated mortality. Moreover, bococizumab was recently suspended due to its higher immunogenicity with time, resulting in less efficacy with long-term use. Alternatives to statins are PCSK9 inhibitors which are administered subcutaneously every two or four weeks. They are injectables with considerable lipid-lowering properties. This narrative review discusses their genetics, safety, tolerability, and cost-effectiveness. It also quantifies their benefit in certain subgroups by analyzing the findings from recent randomized clinical trials. Current data from phase 2 and 3 trials (ORION, ODYSSEY, and FOURIER) suggest a favorable profile for evolocumab, alirocumab, and inclisiran with minimal tolerable side effects and superior efficacy in statin-intolerant patients. Their cost-effectiveness has not yet been established clearly, but future outcomes seem promising.
BACKGROUND: Lipid profile and its related ratios such as total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), TG/HDL-C ratio, TC/HDL-C rati...BACKGROUND: Lipid profile and its related ratios such as total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), triglyceride (TG), high-density lipoprotein-cholesterol (HDL-C), TG/HDL-C ratio, TC/HDL-C ratio, LDL-C/HDL-C ratio, white blood cell (WBC)/HDL-C ratio, and fasting blood glucose (FBG)/HDL-C ratio are valuable indicators that have been studied in various disorders to predict mortality. The present study was conducted with the aim of investigating the role of lipid profile ratios in predicting mortality in COVID-19 patients. METHODS: At the beginning of hospitalization, laboratory tests were taken from all patients ( = 300). The ability of lipid profile ratios to determine the COVID-19 severity was evaluated using receiver-operating characteristic (ROC). In addition, survival probability was determined with the average of Kaplan-Meier curves, so that the end point was death. RESULTS: In deceased patients, TG, TC, LDL-C, HDL-C, TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C parameters were significantly lower than those of surviving patients, while WBC/HDL-C and FBG/HDL-C were significantly higher. TC (HR = 3.178, 95%CI = 1.064 to 9.491, < 0.05), TG (HR = 3.276, 95%CI = 1.111 to 9.655, < 0.05), LDL-C (HR = 3.207, 95%CI = 1.104 to 9.316, < 0.05), and HDL-C (HR = 3.690, 95%CI = 1.290 to 10.554, < 0.05), as well as TC/HDL-C (HR = 3.860, 95%CI = 1.289 to 11.558, < 0.05), TG/HDL-C (HR = 3.860, 95%CI = 1.289 to 11.558, < 0.05), LDL-C/HDL-C (HR = 3.915, 95%CI = 1.305 to 11.739, < 0.05), WBC/HDL-C (HR = 3.232, 95%CI = 1.176 to 8.885, < 0.05), and FBG/HDL-C ratios (HR = 4.474, 95%CI = 1.567 to 12.777, < 0.01), were detectably related to survival. The multivariate Cox regression models showed that only FBG/HDL-C ratio (HR = 5.477, 95%CI = 1.488 to 20.153, < 0.01) was significantly related to survival. CONCLUSION: The results suggested that FBG/HDL-C ratio in hospital-admitted COVID-19 patients was a reliable predictor of mortality.
Airway remodeling (AR) increases disease severity, and morbidity of asthmatic patients by contributing to irreversible airflow obstruction and progressive declines in lung function. Arginase isoenzymes and the downstream...Airway remodeling (AR) increases disease severity, and morbidity of asthmatic patients by contributing to irreversible airflow obstruction and progressive declines in lung function. Arginase isoenzymes and the downstream enzymes ornithine decarboxylase (ODC) and ornithine aminotransferase (OAT) have been implicated in the hyperplastic and fibrotic changes of AR, respectively. Omega-3 polyunsaturated fatty acids (-3 PUFAs) and resolvin metabolites have anti-AR effects, but whether they are mediated through the arginase pathway is unclear. Our study intended to determine the effects of the -3 PUFAs eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), resolvin D1 (RvD1), T1 cytokines, acetylsalicylic acid (ASA), cAMP, and dexamethasone (DEX) on the expression of arginase isoenzymes arginase 1 (ARG1) and arginase 2 (ARG2), ODC, and OAT in human lung fibroblasts (HLF) from normal (NHLF) and diseased (DHLF) asthmatic donors using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). Our data showed that EPA and EPA+DHA downregulated ARG2 mRNA 2-fold in both types of HLF. DHA, RvD1, and DEX did not alter mRNA levels for any of the genes studied. EPA lowered the ARG2 protein levels in DHLF, but did not affect those levels in NHLF. ASA upregulated ARG2 mRNA 5-fold and 7-fold in NHLF and DHLF, respectively, T1 cytokines downregulated ARG2, ODC, and OAT mRNA in DHLF 10-fold, 2-fold, and 2.5-fold, respectively, and cAMP downregulated ARG2 mRNA 2-fold in DHLF. These results are the first to show a direct effect of -3 PUFAs on ARG2 mRNA levels and provide further evidence for a role of -3 PUFAs in AR.
OBJECTIVE: The aim of this study was to determine the chemical characteristics and antibacterial activity of liver oil against the bacteria responsible for food poisoning. METHODS: Oils were extracted from liver using...OBJECTIVE: The aim of this study was to determine the chemical characteristics and antibacterial activity of liver oil against the bacteria responsible for food poisoning. METHODS: Oils were extracted from liver using two methods (exudation and cooking-pressing) and analyses by Fourier transform infrared (FTIR) spectroscopy. Quality indexes were determined using standard methods and the fatty acid profile was carried out by gas chromatography with a flame ionization detector (GC-FID). Antibacterial activities of these oils, their emulsion, and their interactions with common antibiotics were evaluated by the broth microdilution method. RESULTS: Extraction yield was higher with cooking-pressing (16.90%) compared to exudation (14.49%). The quality indexes of both oils were conformed to Codex Alimentarius Standard. Thiobarbituric acid index was higher with exudation compared to cooking-pressing (3.20 ± 0.14 and 2.36 ± 0.14 mol MDA/kg, respectively) while acid, iodine, peroxide, and anisidine values did not significantly vary with the extraction methods (2.15-2.30 mgKOH/g, 102.42-106.65 gI/100 g, 3.34-3.57 meqO/kg, and 2.85-3.32 respectively). FTIR analyses clearly show that the two spectra are similar (no differences in the frequency and absorbance of their bands). The fatty acid profile revealed that, regardless of the extraction methods, oil is richer in monounsaturated (55.97-55.41%) followed by polyunsaturated (28.17-28.52%) and saturated fatty acids (15.86-16.07%). Moreover, these oils showed antibacterial activity on all the bacteria strains tested with MICs between 16 and 256 mg/ml. Regardless of the extraction methods, emulsions showed higher activity (6.25 ≤ MIC ≤25 mg/ml) compared to crude oils. Additionally, liver oil potentiated the antibacterial activity of ciprofloxacin, tetracycline, gentamicin, amoxicillin, and chloramphenicol. CONCLUSION: These results showed the effectiveness of liver oil against some bacteria responsible for food poisoning, thus demonstrating their antibacterial properties which could be due to their chemical composition.
This pilot study aimed to determine early changes of LXA levels among the hospitalized patients confirmed as COVID-19 cases following the clinical management and its correlation with commonly used inflammatory markers, i...This pilot study aimed to determine early changes of LXA levels among the hospitalized patients confirmed as COVID-19 cases following the clinical management and its correlation with commonly used inflammatory markers, including erythrocyte sedimentation rate (ESR), c-reactive protein (CRP), and ferritin. Thirty-one adult hospitalized patients infected with the non-severe COVID-19 were included. LXA levels were measured at the baseline and 48-72 hours after hospitalization. Accordingly, ESR and CRP levels were collected on the first day of hospitalization. Moreover, the maximum serum ferritin levels were determined during the five days. LXA levels significantly increased at 48-72 hours compared to the baseline. ESR, CRP, and ferritin levels were positively correlated with the increased LXA4. In contrast, aging was shown to negatively correlate with the increased LXA levels. LXA may be known as a valuable marker to assess the treatment response among non-elderly patients with non-severe COVID-19. Furthermore, LXA could be considered as a potential treatment option under inflammatory conditions. Further studies are necessary to clarify LXA role in COVID-19 pathogenesis, as well as the balance between such pro-resolving mediators and inflammatory parameters.