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Sugar-sweetened beverage (SSB) and fruit juice (FJ) consumption may promote lipid abnormalities in childhood. We examined the association between SSB/FJ intake and lipid levels using electronic health record data for 2816 adolescents. Multivariable logistic regression models treated clinical cutpoints for abnormal lipid levels (triglycerides [TG], high-density lipoprotein (HDL), low-density lipoprotein [LDL], and total cholesterol) as dependent variables. In models not adjusted for adiposity, elevated SSB and FJ consumption was associated with increased odds of having abnormally high TG (SSB: odds ratio [OR] = 1.28 (95% confidence interval [CI] = [1.07-1.52], P =.007); FJ: 1.35 ([1.09-1.69], P =.007)) and abnormally low HDL (SSB: 1.47 ([1.17-1.86], P =.001); FJ: 1.35 ([1.02-1.78], P =.03)). Adjusting for adiposity, a likely mediator of the relationship, attenuated these associations. These findings support the need for identifying unhealthy beverage consumption habits during childhood health care visits as a modifiable behavior associated with cardiometabolic risk. [ABSTRACT FROM AUTHOR]

Background: Artichoke (Cynara scolymus L.) has the potential to treat diabetes, dyslipidemia, hypertension, and obesity. However, the evidence from previous studies is not consistent. Objectives: This meta-analysis evaluated the efficacy of products derived from artichokes on blood glucose, lipid level, blood pressure, and anthropometric parameters. Methodology: The literature was reviewed via international databases (PubMed, ScienceDirect, and Scopus). A total of 21 RCTs with high quality, assessed by the Cochrane risk-of-bias tool, were included. Results: Artichoke was linked to a significant reduction in fasting blood sugar (FBS) (WMD: −3.76 mg/dL: 95%CI −7.31, −0.22), insulin level (WMD: −1.35 mIU/L: 95%CI −2.29, −0.41), and HOMA-IR (WMD: −1.00: 95%CI −1.95, −0.06). Similar results were observed for LDL-c (WMD: −12.94 mg/dL: 95%CI −18.02, −7.87), total cholesterol (TC) (WMD: −19.64 mg/dL: 95%CI −23.94, −15.35), and triglyceride (TG) (WMD: −13.36 mg/dL: 95%CI −19.06, −7.66). Moreover, participants who administered artichoke experienced a significant reduction in SBP (WMD: −1.59 mmHg: 95%CI −3.02, −0.16), body weight (BW) (WMD: −1.17 kg: 95%CI −1.75, −0.60), and BMI (WMD: −0.30 kg/m2: 95%CI −3.02, −0.16). Conclusion: Artichoke may improve blood glucose, lipid profile, blood pressure, and anthropometric parameters. A large, well-designed RCT and head-to-head comparison using a standardized preparation of artichoke will provide definitive data on specific participants. [ABSTRACT FROM AUTHOR]

Lipid-lowering therapies, particularly non-statin regimens, are underutilized as ~2/3 of patients with atherosclerotic cardiovascular (CV) disease (CVD) are not optimally managed, and do not attain target low-density lipoprotein cholesterol (LDL-C) concentrations, despite statin treatment. Statins have been the mainstay of hypolipidemic therapies; however, they are plagued by adverse effects, which have partly hindered their more widespread use. Ezetimibe is often the first added mode of treatment to attain LDL-C goals as it is efficacious and also allows the use of a smaller dose of statin, while the need for more expensive therapies is obviated. We herein provide a comprehensive review of the effects of ezetimibe in lipid lowering and reducing CV events and improving outcomes. Of the hypolipidemic therapies, oral ezetimibe, in contrast to newer agents, is the most convenient and/or affordable regimen to be utilized as mono- or combined therapy supported by data from CV outcomes studies attesting to its efficacy in reducing CVD risk and events. When combined with a statin, the statin dose could be lower, thus curtailing side-effects, while the hypolipidemic effect is enhanced (by ~20%) as the percentage of patients with target level LDL-C (<70 mg/dL) is higher with combined treatment versus a high-intensity statin. Ezetimibe could also serve as an alternative treatment in cases of statin intolerance. In conclusion, ezetimibe has an excellent safety/tolerability profile; it is the first added treatment to a statin that can attain LDL-C targets. In the combined therapy, the hypolipidemic effect is enhanced while the dose of statin could be lower, thus limiting the occurrence of side-effects. Ezetimibe could also serve as an alternative mode of treatment in cases of statin intolerance. [ABSTRACT FROM AUTHOR]

Background: Lipoprotein(a) (Lp(a)) is now established as a causal risk factor for cardiovascular disease (CVD) and accurate laboratory measurement is of pivotal importance in reducing Lp(a) associated risk. The consensus statement by HEART UK in 2019 included recommendations to improve standardisation of clinical laboratory measurement and reporting of Lp(a). Methods: A 16 question, electronic audit survey was circulated to 190 accredited clinical biochemistry laboratories to assess the adoption of these recommendations in the UK. Results: Responses were received from 65 of 190 laboratories (34%). Only 5 (8%) did not offer Lp(a) measurement. Of those providing the test, 23% (n = 14) offered an in-house service (IHS), the remaining laboratories (77%; n = 46) used an external referral service (ERS). The majority (10 of 14 or 71%) of IHS laboratories responded with details of their method, stating whether it minimised sensitivity to the effect of Lp(a) isoform size and used calibrators certified for traceability to the WHO/IFCC reference material, however, only a minority ERS laboratories (13 of the 46 or 28%) were able to specify the method used by their referral laboratory. Of the laboratories who specified their reporting units, 6 of 10 IHS and 7 of 23 ERS laboratories reported in nmol/L. Among the 60 laboratories who responded, the HEART UK recommendations appear to have been adopted in full by only 3 IHS laboratories. Conclusions: Further efforts are needed to standardise the measurement and reporting of Lp(a) so that results and interpretation are comparable across clinical biochemistry laboratories in the UK. [ABSTRACT FROM AUTHOR]

Background: Despite an acute knee injury being a major risk factor for osteoarthritis, the factors that initiate and maintain this risk of longer-term knee symptoms are poorly understood. Bioactive lipids derived from omega-3 and -6 polyunsaturated fatty acids have key roles in the regulation of the inflammatory response and have been linked to joint damage and osteoarthritis pain in translational models. Hypothesis: There would be associations between systemic levels of bioactive lipids and knee symptoms longitudinally after an acute knee injury and related knee surgery. Study Design: Controlled laboratory study. Methods: This study analyzed a subset of young, active adults who had sustained an acute knee injury (recruited via a surgical care pathway) and healthy age- and sex-matched controls. Surgery, if performed, was conducted after the baseline serum sample was taken and before the 3-month and 2-year visits. Liquid chromatography–tandem mass spectrometry of 41 bioactive lipids was carried out in sera of (1) 47 injured participants (median age, 28 years) collected at baseline (median, 24 days after injury), 3 months, and 2 years, along with the Knee injury and Osteoarthritis Outcome Score, and (2) age- and sex-matched controls. Results: Levels of the omega-3 polyunsaturated fatty acids eicosapentaenoic acid (P ≤.0001) and docosahexaenoic acid (P ≤.0001) and the pro-resolving lipid mediators 17– and 14–hydroxydocosahexaenoic acid, and 18-hydroxyeicosapentaenoic acid were all significantly greater at baseline in injured participants compared with the later time points and also higher than in healthy controls (P =.0019 and P ≤.0001, respectively). Levels of pro-inflammatory prostaglandins E2 and D2, leukotriene B4, and thromboxane B2 were significantly lower at baseline compared with the later time points. Higher levels of 8,9–, 11,12–, and 14,15–dihydroxyeicosatrienoic acid (DHET) were cross-sectionally associated with more severe knee pain/symptoms according to the Knee injury and Osteoarthritis Outcome Score at 2 years (P =.0004, R 2 = 0.251; P =.0002, R 2 = 0.278; and P =.0012, R 2 = 0.214, respectively). Conclusion: The profile of pro-resolving versus pro-inflammatory lipids at baseline suggests an initial activation of pro-resolution pathways, followed by the later activation of pro-inflammatory pathways. Clinical Relevance: In this largely surgically managed cohort, the association of soluble epoxide hydrolase metabolites, the DHETs, with more severe knee symptoms at 2 years provides a rationale for further investigation into the role of this pathway in persisting knee symptoms in this population, including potential therapeutic strategies. [ABSTRACT FROM AUTHOR]

One means by which cells reutilize neutral lipids stored in lipid droplets is to degrade them by autophagy. This process involves spartin, mutations of which cause the rare inherited disorder Troyer syndrome (or spastic paraplegia-20, SPG20). A recently published paper from the team led by Karin Reinsich (Yale) suggests that the molecular function of spartin and its unique highly conserved "senescence" domain is as a lipid transfer protein. Spartin binds to and transfers all lipid species found in lipid droplets, from phospholipids to triglycerides and sterol esters. This lipid transfer activity correlates with spartin's ability to sustain lipid droplet turnover. The senescence domain poses an intriguing question around the wide range of its cargoes, but intriguingly it has yet to yield up its secrets because attempts at crystallization failed and AlphaFold's prediction is unconvincing. [ABSTRACT FROM AUTHOR]

Background: With the development and wide application of next-generation sequencing (NGS), multiple-gene mutations related to lung cancer are detected using this technology. Notably, even multigene concomitant mutations (co-mutations), which occur at a relatively low incidence, can be detected more effectively using NGS. It is well-known that the percentages of non-small cell lung cancer (NSCLC) in the elderly lung cancer population are also gradually increasing, while its prognosis is hard and the quality of long-term survival is poor. This study aimed at investigating the common clinicopathologic features of multigene co-mutations for better evaluating the prognosis of elderly NSCLC patients. Methods: A total of 464 NSCLC patients were divided into 3 groups according to the types of gene mutation, whose clinical data were retrospectively analyzed. Results: In total, 38.36% (178/464) of NSCLC patients were in the nonmutation group, 50% in the single-gene mutation group, and 11.64% in the multigene co-mutation group. Nonmutation, single-gene mutation, and co-mutation groups were all prone to occur in male adenocarcinoma patients (P <.05). EGFR gene mutation rates were the highest in the single-gene mutation and co-mutation groups (54.31% and 24.35%). In the co-mutation group, the incidence of EGFR/PIK3CA, LK/KRAS, and EGFR/MET co-mutations was the highest (16.67%, 11.11%, and 7.41%). ALK/HER2/MET, EGFR/HER2/MET, and EGFR/HER2/MET/ROS1 multiple-gene co-mutations were, respectively, found in 1 case, and the multigene co-mutation patients commonly had a worse median progression-free survival (PFS) than that of single-gene mutation (7.13 vs 12.34 months, P =.013). Conclusion: With the application of NGS, the detectable rates of gene co-mutation are increasingly high in elderly patients with NSCLC, which mainly occurs in male adenocarcinoma patients commonly with poor PFS. It will be critically necessary to conduct multigene detections by NGS for directing targeted therapy of elderly NSCLC patients. [ABSTRACT FROM AUTHOR]

The present study investigated the toxic effects of sub-chronic exposure to copper quinolate (CuQ) fungicide on liver and kidney function. Twenty-four adult male Wistar rats were equally divided into a control group, and three treated groups received, respectively, by oral gavage, three increasing doses of CuQ: 47; 67.1; and 94 mg/kg b.w corresponding, respectively, LD50/100, LD50/70, and LD50/50 daily for 8 weeks. CuQ resulted in a significant increase in the serum enzymatic activity of aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), and the serum levels of urea, creatinine, uric acid, and malondialdehyde, along with a marked decrease in alanine aminotransferase (ALT) activity, and the contents of total protein and albumin compared to those of the control group. Furthermore, glutathione content and the enzymatic activity of superoxide dismutase (SOD), catalase (CAT), glutathione S-transferase (GST), and glutathione peroxidase (GPx) decreased significantly in a dose-dependent manner with respect to CuQ. The adverse effects of CuO were supported by the histopathological evaluations of liver and kidney tissues. Conclusively, sub-chronic CuQ exposure was shown to induce kidney and liver oxidative damage and dysfunction. [ABSTRACT FROM AUTHOR]

In this study, Mediterranean mussels (Mytilus galloprovincialis) coming from Italian production were purchased in the most important Italian wholesale fish market in different seasons. Biometrical parameters and chemical composition were investigated, with a particular focus on lipid quality and fatty acids (FAs) composition. Results showed a valuable nutritional profile independently by the season of production, represented by high protein and low-fat content, with the lipid portion represented by high amounts of beneficial FAs, particularly the long chain of the n-3 series. Some differences (p < 0.05) were found in carbohydrates and fat content of mussels edible tissues and in FAs profile of specimens collected in different seasons. The most favourable composition in terms of lipid quality was found in mussels collected during spring, corresponding to the moment of the year when mussels store energy reserves in the form of carbohydrates and fat (preparing for the spawning events) and when seawater is enriched in phytoplankton. The lipid health indices calculated (n6/n3, AI, TI) showed optimal values independently by the season of production. The outcomes obtained in this study could help supporting the appreciation of Mediterranean mussels as nutritional valuable seafood product, thus helping encouraging their consumption and promoting the appraisal of this farming sector essential for Italian aquaculture and related to low environmental impact. [ABSTRACT FROM AUTHOR]

Current study aims to evaluate the effect of essential oil on the conservation of chicken fillets. Following a screening, Tetraclinis articulata was selected for its antimicrobial (Enterococcus feacalis ATCC 29212, MIC < 0.031 mg/mL) and antioxidant (IC50 = 1000 µg/mL) potentials with no cytotoxicity effect towards murine macrophage cells. The treatment of chicken fillets, especially with 200 ppm of T. articulata essential oil per 100 g of product reduced significantly (p < 0.05) lipid oxidation during 12 days of refrigerated storage. Microbial flora charges decreased significantly (p < 0.05) with a rate of 50.31% for 200 ppm of essential oil from the 6th day of storage. The acidity of treated fillets was lower than control samples (1.3 g/kg) from the 3rd day of storage. In addition, a clear effect was recorded by reducing water losses during cooking under the tested doses of essential oil. Withall, findings encouraged the use of T. articulata to extend poultry meat product shelf life. [ABSTRACT FROM AUTHOR]

The aerobic organisms not only need oxygen for survival, but oxygen is also fundamentally malignant to the aerobic organism on the grounds of free radical generation and their affiliation with free oxidative stress. This study was done to evaluate the antioxidant and protective properties of P kurroa, S aromaticum, L inermis, R emodi, and C longa against lipid peroxidation induced by different pro-oxidants. The aqueous extracts of these medicinal plants showed inhibition against thiobarbituric acid reactive species (TBARS) induced by different pro-oxidants (10 mM FeSO4 and 5 mM sodium nitroprusside) in the brain and liver of mice. Moreover, the free radical scavenging activities of the extracts were evaluated by the scavenging of the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. L inermis, S aromaticum, and R emodi showed higher inhibitory effects, which could be attributed to their significantly reduced ability and free radical scavenging activities. Therefore, the oxidative stress in the brain and liver could be potentially managed or prevented by the dietary intake of L inermis, S aromaticum, and R emodi plants, which justifies the use of these plants in various degenerative diseases. C longa and P kurroa showed relatively weak antioxidant activities. [ABSTRACT FROM AUTHOR]

This study is taken up to evaluate the effect of an exercise program on adolescents' obesity and overweight profile. For this purpose, a 1-group pretest-posttest study was conducted with 72 adolescents who underwent a physical activity program supervised by one health professional 5 times a week; the sessions were distributed over 12 weeks and lasted from 50 to 60 minutes. The primary outcomes were anthropometric measurements, whereas the secondary outcomes were lipid profile, blood glucose, and blood pressure. Outcomes were assessed before the intervention and 1 day after the program ended; significance was established at P <.05. As a result, a significant improvement was verified in all the primary outcomes (P <.001) and in most secondary outcomes (capillary blood glucose, P =.0001; triglycerides, P =.0001; and systolic blood pressure, P =.005). In conclusion, the supervised exercise program significantly reduced anthropometric measurements and blood glucose, triglycerides, and systolic blood pressure levels. [ABSTRACT FROM AUTHOR]

Background: It is still unelucidated how hormonal alterations affect developing organisms and their descendants. Particularly, the effects of androgen levels are of clinical relevance as they are usually high in women with Polycystic Ovary Syndrome (PCOS). Moreover, it is still unknown how androgens may affect males' health and their descendants. Objectives: We aimed to evaluate the multigenerational effect of prenatal androgen excess until a second generation at early developmental stages considering both maternal and paternal effects. Design And Methods: This is an animal model study. Female rats (F0) were exposed to androgens during pregnancy by injections of 1 mg of testosterone to obtain prenatally hyperandrogenized (PH) animals (F1), leading to a well—known animal model that resembles PCOS features. A control (C) group was obtained by vehicle injections. The PH-F1 animals were crossed with C males (m) or females (f) and C animals were also mated, thus obtaining 3 different mating groups: Cf × Cm, PHf × Cm, Cf × PHm and their offspring (F2). Results: F1-PHf presented altered glucose metabolism and lipid profile compared to F1-C females. In addition, F1-PHf showed an increased time to mating with control males compared to the C group. At gestational day 14, we found alterations in glucose and total cholesterol serum levels and in the placental size of the pregnant F1-PHf and Cf mated to F1-PHm. The F2 offspring resulting from F1-PH mothers or fathers showed alterations in their growth, size, and glucose metabolism up to early post-natal development in a sex-dependent manner, being the females born to F1-PHf the most affected ones. Conclusion: androgen exposure during intrauterine life leads to programing effects in females and males that affect offspring health in a sex-dependent manner, at least up-to a second generation. In addition, this study suggests paternally mediated effects on the F2 offspring development. [ABSTRACT FROM AUTHOR]

The analytical performance of a compact infrared attenuated total reflection spectrometer using a pyroelectric detector array has been evaluated and compared to a conventional laboratory Fourier transform infrared system for applications in food analysis. Analytical characteristics including sensitivity, repeatability, linearity of the calibration functions, signal-to-noise ratio, and spectral resolution have been derived for both approaches. Representative analytes of relevance in food industries (i.e., organic solvents, fatty acids, and mycotoxins) have been used for the assessment of the performance of the device and to discuss the potential of this technology in food and feed analysis. Graphical Abstract This is a visual representation of the abstract. [ABSTRACT FROM AUTHOR]

Objective: The aim of this systematic review and meta-analysis of randomised controlled trials is to evaluate the impact of pharmacist-led interventions on cardiovascular disease (CVD) risk factors among patients with type 2 diabetes. Method: A literature review was conducted according to PRISMA guidelines using 4 electronic databases: Embase, MEDLINE, CINHAL and the Cochrane Central Register of Controlled Trials. We searched for pharmacist interventions among adults with type 2 diabetes and cardiovascular disease in randomised controlled trials from inception to May 2021 in primary care, diabetes clinics and hospitals. The clinical outcomes measured glycosylated haemoglobin (HbA1c), blood pressure (BP) and lipid profile. The non-clinical outcomes included medication adherence, smoking, health-related quality of life and the cost of the intervention. For the meta-analysis, clinical outcomes were pooled with the random effect model in RevMan 5.3. The Cochrane risk-of-bias tool was used to assess the quality of the included studies. Results: We retrieved 223 studies,141 of which were included in the review. Ten published articles met the inclusion criteria and were included in the meta-analysis. The pharmacists delivered the interventions alone or collaboratively with other healthcare professionals in hospitals or similar settings. The overall result showed a significant reduction in HbA1c (n = 10; standard deviation in mean value [SDM]: −.53%, 95% CI: −.84, −.23) and systolic BP (n = 10; [SDM]: −.35 mmHg, 95% CI: −.51, −.20) in pharmacist intervention groups. For the non-clinical outcomes, the review revealed variable results from pharmacist intervention compared with those standard care. Conclusion: Pharmacy interventions provide evidence for pharmacists' decisive role in diabetes care management and reducing cardiovascular risk factors among adults with type 2 diabetes. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the astaxanthin-loaded nanostructured lipid carriers (ASX-NLC) prepared using a high-pressure homogenization transport system for local application of astaxanthin. Dynamic light scattering (DLS) and X-ray diffraction (XRD) were used to study the effect of microencapsulation on the properties of ASX-NLC. The mean size of ASX-NLC was about 108.43 ± 0.26 nm and PdI was 0.176 ± 0.002. The ASX-NLC had high encapsulation efficiency which was 95.69 ± 0.13%. Good light stability and temperature stability were shown at the ASX-NLC, indicating that the preparation process was feasible. The 2,2-diphenyl-1-pyridylohydrazinyl (DPPH) scavenging test showed that ASX-NLC could still play an antioxidant role. In vitro release studies showed that compared with an astaxanthin ethanol solution, an ASX-NLC could maintain astaxanthin release more effectively. In vitro permeation studies showed that ASX-NLC could increase astaxanthin retention in the skin. In conclusion, ASX-NLC could significantly enhance astaxanthin accumulation during dermal applications. The research results have important reference significance for local skin applications and provide a basis for the development of nanostructured lipid carriers. ASX-NLC might be suitable carriers for the local application of astaxanthin. Graphical Abstract [ABSTRACT FROM AUTHOR]

The effectiveness of commercial oxygen scavengers was investigated in order to increase the shelf-life of sliced dry-cured Iberian shoulder in MAP (modified atmosphere packaging) for up to 150 days. Five dry-cured shoulders from Iberian pigs were used. Slices of these dry-cured shoulders were randomly packaged in MAP conditions. An active packaging (AP) with oxygen scavengers was evaluated to reduce the level of oxygen within the headspace as close to 0% as possible. AP was compared to a Control Treatment (C) (without scavenger). Sliced dry-cured Iberian shoulder in AP showed lower thiobarbituric acid reactive substances values (TBARS) than control packages after 150 days of storage, and in general, volatile compounds derived from lipid oxidation, increased in C packages, whereas these remained steady in AP. Therefore, AP was effective to decrease the development of lipid oxidation during storage. In contrast, AP was not effective in preserving color changes, although no sensory differences between treatments were appreciated by the panelists. [ABSTRACT FROM AUTHOR]

Background: Leaves, flowers and young shoots of yellow Camellia species are often used as a substitute for green tea in Vietnam. Yellow Camellia species contain high levels of polyphenol compounds, and have shown activities such as antioxidant, anticancer, and cytotoxic. Objectives: We qualitatively screened phytochemicals, quantified total polyphenols of 70% ethanol (EtOH) extracts of leaves, young shoots, and flowers of Camellia vuquangensis and Camellia hatinhensis in Ha Tinh Province, Vietnam. Furthermore, these extracts have been evaluated for lipid peroxidation inhibitory activities at the in vivo level in the BALB/c mouse model, and in vitro cytotoxic activities. Materials and Methods: Chemical methods and thin-layer chromatographic (TLC) analysis were used for the qualitative screening of phytochemicals. High-performance liquid chromatography (HPLC) was used to determine total polyphenols. Cell survival was determined through optical density (OD) measured when the protein composition of the cells was stained with sulforhodamine B (SRB). Inhibition of lipid peroxidation was evaluated by determining the content of malondialdehyde (MDA), which is a product of membrane lipid peroxidation. Results: The total polyphenol contents of all parts of the two species were comparable to that of green tea with values between 319.3 and 342.6 mg gallic acid equivalents (GAE/g) dry weight. Extracts of leaves, flowers of C. vuquangensis and C. hatinhensis showed strong lipid peroxidation inhibitory activities (IC50: 7.92–17.45 µg/mL) and moderate cytotoxic activities against cell lines HepG2, A549, MCF7, SK-Mel-2, HT-29, and AGS (IC50: 34.73–80.58 µg/mL). Conclusion: These two tea species may be considered as herbal teas with various health benefits. [ABSTRACT FROM AUTHOR]

Background: Dyslipidaemia is an important cardiovascular risk factor for people with severe mental illness, contributing to premature mortality. The link between antipsychotics and dyslipidaemia is well established, while evidence on antidepressants is mixed. Aims: To investigate if antidepressant/antipsychotic use was associated with lipid parameters in UK Biobank participants and if CYP2C19 and CYP2D6 genetic variation plays a role. Methods: Review of self-reported prescription medications identified participants taking antidepressants/antipsychotics. Total, low-, and high-density lipoprotein cholesterol (L/HDL-C) and triglycerides derived from blood samples. CYP2C19 and CYP2D6 metabolic phenotypes were assigned from genetic data. Linear regression investigated aims, adjusted for key covariates. Results: Of 469,739 participants, 36,043 took antidepressants (53% female, median age 58, 17% taking cholesterol-lowering medications) and 3255 took antipsychotics (58% female, median age 57, 27% taking cholesterol-lowering medications). Significant associations were found between use of each amitriptyline, fluoxetine, citalopram/escitalopram, sertraline, paroxetine and venlafaxine with higher total cholesterol, LDL-C, and triglycerides and lower HDL-C, compared to participants not taking each medication. Venlafaxine was associated with the worst lipid profile (total cholesterol, adjusted mean difference: 0.21 mmol/L, 95% confidence interval (CI): 0.17 to 0.26, p < 0.001). Antipsychotic use was significantly associated with lower HDL-C and higher triglycerides. In participants taking sertraline, CYP2C19 intermediate metabolisers had higher HDL-C (0.05 mmol/L, 95% CI: 0.01 to 0.09, p = 0.007) and lower triglycerides (−0.17 mmol/L, 95% CI: −0.29 to −0.05, p = 0.007), compared to normal metabolisers. Conclusions: Antidepressants were significantly associated with adverse lipid profiles, potentially warranting baseline and regular monitoring. Further research should investigate the mechanistic pathways underlying the protective effects of the CYP2C19 intermediate metaboliser phenotype on HDL-C and triglycerides in people taking sertraline. [ABSTRACT FROM AUTHOR]

In many industrial processes, worker exposure to cadmium causes kidney damage; thus, protection against cadmium toxicity is important in workplace health. Cadmium toxicity involves oxidative stress by increasing the levels of reactive oxygen species. Statins have shown antioxidant effects that might prevent this increase in oxidative stress. We investigated the potential effects of atorvastatin pretreatment in protecting experimental rats against kidney toxicity caused by cadmium. Experiments were performed on 56 adult male Wistar rats (200 ± 20 g), randomly assigned to eight groups. Atorvastatin was administered by oral gavage for 15 days at 20 mg/kg/day, starting 7 days before cadmium chloride intra-peritoneal administration (at 1, 2, and 3 mg/kg) for 8 days. On day 16, blood samples were collected, and kidneys were excised to evaluate the biochemical and histopathological changes. Cadmium chloride significantly increased malondialdehyde, serum creatinine, blood urea nitrogen, and decreased superoxide dismutase, glutathione, and glutathione peroxidase levels. Pre-administration of rats with atorvastatin at a dose of 20 mg/kg decreased blood urea nitrogen, creatinine, and lipid peroxidation, increased the activities of antioxidant enzymes, and prevented changes in physiological variables compared with animals that were not pretreated. Atorvastatin pretreatment prevented kidney damage following exposure to toxic doses of cadmium. In conclusion, atorvastatin pretreatment in rats with cadmium chloride-induced kidney toxicity could reduce oxidative stress by changing biochemical functions and thereby decreasing damage to kidney tissue. [ABSTRACT FROM AUTHOR]

Background: Statins have an important role in stroke prevention, especially in high-risk populations and may also affect the initial stroke severity and outcomes in patients taking them before an ischemic stroke. Aims: Our aim was to evaluate the association of statin pre-treatment with the severity in acute ischemic stroke (AIS). Methods: We analyzed AIS patients received intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT) and recorded in the SITS International Thrombolysis and Thrombectomy Registry from 2011 to 2017. We identified patients with statin information at baseline. The primary outcome was baseline National Institutes of Health Stroke Scale (NIHSS) score. Secondary outcomes were NIHSS score at 24 h, symptomatic intracerebral hemorrhage (SICH) and functional outcome at 90 days after acute intervention. Multivariable linear and logistic regression and propensity score matching (PSM) was used to quantify the effect of statin pre-treatment. Results: Of 93,849 patients, 23,651 (25.2%) were treated with statins prior the AIS. Statin pre-treatment group was older and had higher comorbidity. Median NIHSS at baseline was similar between groups. In the adjusted and PSM analysis, statin pre-treatment was inversely associated with baseline NIHSS (odds ratio (OR) = 0.77, 95% confidence interval (CI) = 0.6–0.99 and OR for PSM 0.73, 95% CI = 0.54–0.99, p = 0.004) and independently associated with mild stroke defined as NIHSS ⩽8 in adjusted and PSM analysis (OR = 1.21, 95% CI = 1.1–1.34, p < 0.001 and OR for PSM 1.17, 95% CI = 1.05–1.31, p = 0.007). Regarding secondary outcomes, there were no differences in functional outcomes, death nor SICH rates between groups. Conclusion: Prior treatment with statins was associated with lower NIHSS at baseline. However, this association did not translate into any difference regarding functional outcome at 90 days. No association was found regarding SICH. These findings indicate the need of further studies to assess the effect on statin pre-treatment on initial stroke severity. [ABSTRACT FROM AUTHOR]

Ozone, an allotrope of oxygen, is enjoying an increasing interest in the setting and management of the medical adjunct treatment, which is called, maybe too simplistically, "ozone therapy". Ozone is not a medicine, so the word therapy does not properly fit this gaseous molecule. Like many natural compounds, for example plant flavonoids, even ozone interacts with aryl hydrocarbon receptors (AhRs) and, at low doses, it works according to the paradoxical mechanism of hormesis, involving mitochondria (mitohormesis). Ozone, in the hormetic range, exerts cell protective functions via the Nrf2-mediated activation of the anti-oxidant system, then leading to anti-inflammatory effects, also via the triggering of low doses of 4-HNE. Moreover, its interaction with plasma and lipids forms reactive oxygen species (ROS) and lipoperoxides (LPOs), generally called ozonides, which are enabled to rule the major molecular actions of ozone in the cell. Ozone behaves as a bioregulator, by activating a wide population of reactive intermediates, which usually target mitochondria and their turnover/biogenesis, often leading to a pleiotropic spectrum of actions and behaving as a tuner of the fundamental mechanisms of survival in the cell. In this sense, ozone can be considered a novelty in the medical sciences and in the clinical approach to pharmacology and medical therapy, due to its ability to target complex regulatory systems and not simple receptors. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to examine the association between serum complement 1q (C1q) and the associated factors of acute ischemic stroke in patients with type 2 diabetes (T2DM). Methods: The baseline clinical variables of the participants were collected, and the levels of blood lipids, blood sugar, inflammatory cytokines, and C1q in the three groups were then compared. The variables which affected the associated factors of acute ischemic stroke in T2DM cases were determined. Results: The levels of C1q in the DAIS group were increased significantly compared with those in the T2DM group. Receiver operating characteristic curve analyses showed that the AUC for C1q and the combined diagnosis of acute ischemic stroke were 0.830 (95%CI 0.747–0.914), with a sensitivity of 0.854 and specificity of 0.780. The results of Pearson's correlation analyses demonstrated that C1q was associated positively with low-density lipoprotein cholesterol (LDL-C), fasting blood glucose (PBG), 2-h postprandial blood glucose (2h PG), and high-sensitive C reaction protein (hs-CRP) (all p <.05). Stratified analysis showed that there was a positive relationship between C1q and the associated factors of acute ischemic stroke for partial LDL-C, and hs-CRP strata. Logistic model analysis suggested that C1q was an independent risk factor for acute ischemic stroke in patients with T2DM. After adjusting for potential confounders, a one-standard deviation (SD) increase in C1q level was strongly related to an approximately 1.5-fold increased risk of acute ischemic stroke in cases with a hs-CRP ≥1.78 mg/L. Conclusion: In DAIS patients, the levels of C1q were increased significantly and were an independent associated factor which affected the occurrence of acute ischemic stroke. [ABSTRACT FROM AUTHOR]

Corynetoxins, members of the tunicamycin group of antibiotics, are produced by the bacterium, Rathayibacter toxicus. They cause a severe neurologic disorder in domestic livestock, are hepatotoxins, and can damage retinal photoreceptors. For these toxins to be ingested by livestock, the bacterium must first be transported onto host plants by adhering to nematode larvae. In the infected seed heads, bacterial galls (gumma) then form. While corynetoxicity occurs most commonly in Australia, it has occurred sporadically in other countries and, due to the widespread global distribution of the bacterium, nematode, and host plants, there is great potential for further spread, particularly as the range of host plant species and nematode vectors identified for R. toxicus is increasing. Since many animal species are susceptible to corynetoxins poisoning, it is likely that humans would also be vulnerable if exposed to these potent, lethal toxins. [ABSTRACT FROM AUTHOR]

Ferroptosis is a new type of cell death marked by iron and lipid ROS accumulation. GPX4 is one of the glutathione peroxidases known to regulate ferroptosis tightly. On the other hand, Nrf2 also plays a vital role in ferroptosis as it targets genes related to oxidant defense. Herein, we employed beas-2 human epithelial cells treated with a low concentration of RSL3 to induce ferroptosis. To study the protective role of Nrf2, we used ML385 as its specific inhibitor. A combination of ML385 and a low concentration of RSL3 synergistically induced more toxicity to RSL3. Furthermore, we found that mitochondrial ROS is elevated in ML385 and RSL3 combination group. In addition, Mito TEMPOL application successfully prevents the upregulation of mitochondrial ROS, lipid ROS, reduces the toxicity of RSL3, restores the antioxidant capacity of the cells, and mitochondrial functions reflected by mitochondrial membrane potential and mitochondrial oxidative phosphorylation system (OXPHOS) expression. Altogether, our study demonstrated that Nrf2 inhibition by ML385 induces more toxicity when combined with RSL3 through the elevation of mitochondrial ROS and disruption of mitochondrial function. [ABSTRACT FROM AUTHOR]

Objectives: Kaempferol (KMF), has beneficial effects against hepatic lipid accumulation. In this study, we aimed to investigate molecular mechanism underlying the protective effect of KMF on lipid accumulation. Methods: HepG2 cells were treated with different concentrations of KMF and 0.5 mM palmitate (PA) for 24 h. The mRNA and protein levels of genes involved in lipid metabolism were evaluated using real-time PCR and western blot. The expression of Nrf2 was silenced using siRNA. Results: Data indicated that KMF (20 μM) reversed PA-induced increased triglyceride (TG) levels and total lipid content. These effects were accompanied by down-regulation of the mRNA and protein levels of lipogenic genes (FAS, ACC and SREBP1), and up-regulation of genes related to fatty acid oxidation (CPT-1, HADHα and PPARα). Kaempferol significantly decreased the levels of the oxidative stress markers (ROS and MDA) and enhanced the activities of antioxidant enzymes SOD and GPx in PA-challenged cells. Luciferase analysis showed that KMF increased the transactivation of Nrf2 in hepatocytes. The results also revealed that KMF-mediated activation of Nrf2 target genes was suppressed by Nrf2 siRNA. Furthermore, Nrf2 siRNA abolished the KMF-induced reduction in ROS and MDA levels in PA treated cells. In addition, the inhibitory effect of KMF on TG levels and the mRNA and protein levels of FAS, ACC and SREPB-1 were significantly abolished by Nrf2 inhibition. Nrf2 inhibition also suppressed the KMF-induced activation of genes involved in β oxidation (CPT-1 and PPAR-α). Conclusion: The results suggest that KMF protects HepG2 cells from PA-induced lipid accumulation via activation of the Nrf2 signaling pathway. [ABSTRACT FROM AUTHOR]

Ferroptosis is potential to relieve drug resistance in hepatocellular carcinoma (HCC). Glutathione peroxidase 4 (GPX4) is a critical modulator of ferroptosis. This study discussed the mechanism of GPX4-inhibited ferroptosis in sorafenib resistance in HCC. HCG18 in HCC cells was detected. Sorafenib resistant (SR) cell line Huh7-SR cells were treated with sorafenib (0, 2.5, 5, 7.5, 10 μM). After silencing HCG18 in Huh7-SR cells, cell activity, proliferation and apoptosis were detected. The levels of iron, the concentration of MDA, GSH and lipid reactive oxygen species (ROS) were measured to evaluate the ferroptosis. The downstream mechanism of HCG18 was predicted and verified. Huh7-SR cells were infected with lentivirus sh-HCG18 to establish xenograft tumor model. HCG18 was elevated in HCC cells and associated with sorafenib resistance. Silencing HCG18 inhibited cell proliferation, promoted apoptosis, and impaired sorafenib resistance. Ferroptosis was inhibited in Huh7-SR cells, while silencing HCG18 inhibited sorafenib resistance by promoting ferroptosis. GPX4 overexpression averted the promotion of sh-HCG18 on ferroptosis, thereby reducing sorafenib resistance. HCG18 sponged miR-450b-5p to regulate GPX4. Collectively, Silencing HCG18 inhibits GPX4 by binding to miR-450b-5p, promotes GPX4-inhibited ferroptosis, and averts sorafenib resistance in HCC. [ABSTRACT FROM AUTHOR]

Lipid transfer between organelles requires proteins that shield the hydrophobic portions of lipids as they cross the cytoplasm. In the last decade a new structural form of lipid transfer protein (LTP) has been found: long hydrophobic grooves made of beta-sheet that bridge between organelles at membrane contact sites. Eukaryotes have five families of bridge-like LTPs: VPS13, ATG2, SHIP164, Hobbit and Tweek. These are unified into a single superfamily through their bridges being composed of just one domain, called the repeating beta groove (RBG) domain, which builds into rod shaped multimers with a hydrophobic-lined groove and hydrophilic exterior. Here, sequences and predicted structures of the RBG superfamily were analyzed in depth. Phylogenetics showed that the last eukaryotic common ancestor contained all five RBG proteins, with duplicated VPS13s. The current set of long RBG protein appears to have arisen in even earlier ancestors from shorter forms with 4 RBG domains. The extreme ends of most RBG proteins have amphipathic helices that might be an adaptation for direct or indirect bilayer interaction, although this has yet to be tested. The one exception to this is the C-terminus of SHIP164, which instead has a coiled-coil. Finally, the exterior surfaces of the RBG bridges are shown to have conserved residues along most of their length, indicating sites for partner interactions almost all of which are unknown. These findings can inform future cell biological and biochemical experiments. [ABSTRACT FROM AUTHOR]

Background: Statin therapy is the primary lipid-lowering agent used in peripheral artery disease (PAD) patients. Although the benefits of statins have been described in the literature, most studies have focused on postoperative statin use and outcomes in major upper body vasculature. Our study aimed to assess the impact of statin therapy on postoperative outcomes of lower extremity endovascular interventions including mortality and amputation rates.Methods: American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database from 2012 to 2019 was utilized for this study. Patients were divided into 2 groups: those on preoperative statins (Group I) and those not on statins (Group II). Univariate and multivariate analyses were performed to assess statin's effect on postoperative outcomes.Results: A total of 12,217 patients (72.7%) were in Group I and 4599 patients (27.3%) were in Group II. The distribution of primary outcomes was as follows: Amputation (Group I: 3% vs Group II: 3.9%, P <.05) and Mortality (Group I: 1.6% vs Group II: 1.9%, P = .086). Statin use was associated with decreased amputation rates. Patients with tissue loss were 5 times more likely to undergo amputations (AOR: 5.58 [CI 2.29-13.63] P < .01) within 30-days postoperatively as compared to those whose presenting symptoms were claudication.Conclusion: Statin therapy was associated with a decreased limb loss within 30-days after intervention at the time of lower extremity endovascular intervention. Patients presenting with rest pain and tissue loss had a higher incidence of limb loss than claudicants. [ABSTRACT FROM AUTHOR]

Lipid transfer proteins mediate the exchange of lipids between closely apposed membranes at organelle contact sites and play key roles in lipid metabolism, membrane homeostasis, and cellular signaling. A recently discovered novel family of lipid transfer proteins, which includes the VPS13 proteins (VPS13A-D), adopt a rod-like bridge conformation with an extended hydrophobic groove that enables the bulk transfer of membrane lipids for membrane growth. Loss of function mutations in VPS13A and VPS13C cause chorea acanthocytosis and Parkinson's disease, respectively. VPS13A and VPS13C localize to multiple organelle contact sites, including endoplasmic reticulum (ER) – lipid droplet (LD) contact sites, but the functional roles of these proteins in LD regulation remains mostly unexplored. Here we employ CRISPR-Cas9 genome editing to generate VPS13A and VPS13C knockout cell lines in U-2 OS cells via deletion of exon 2 and introduction of an early frameshift. Analysis of LD content in these cell lines revealed that loss of either VPS13A or VPS13C results in reduced LD abundance under oleate-stimulated conditions. These data implicate two lipid transfer proteins, VPS13A and VPS13C, in LD regulation. [ABSTRACT FROM AUTHOR]

Objective: Clinical heterogeneity in major depressive disorder likely reflects the range of etiology and contributing factors in the disorder, such as genetic risk. Identification of more refined subgroups based on biomarkers such as white matter integrity and lipid-related metabolites could facilitate precision medicine in major depressive disorder. Methods: A total of 148 participants (15 genetic high-risk participants, 57 patients with first-episode major depressive disorder and 76 healthy controls) underwent diffusion tensor imaging and plasma lipid profiling. Alterations in white matter integrity and lipid metabolites were identified in genetic high-risk participants and patients with first-episode major depressive disorder. Then, shared alterations between genetic high-risk and first-episode major depressive disorder were used to develop an imaging x metabolite diagnostic panel for genetically based major depressive disorder via factor analysis and logistic regression. A fivefold cross-validation test was performed to evaluate the diagnostic panel. Results: Alterations of white matter integrity in corona radiata, superior longitudinal fasciculus and the body of corpus callosum and dysregulated unsaturated fatty acid metabolism were identified in both genetic high-risk participants and patients with first-episode major depressive disorder. An imaging x metabolite diagnostic panel, consisting of measures for white matter integrity and unsaturated fatty acid metabolism, was identified that achieved an area under the receiver operating characteristic curve of 0.86 and had a significantly higher diagnostic performance than that using either measure alone. And cross-validation confirmed the adequate reliability and accuracy of the diagnostic panel. Conclusion: Combining white matter integrity in corpus callosum, superior longitudinal fasciculus and corona radiata, and unsaturated fatty acid profile may improve the identification of genetically based endophenotypes in major depressive disorder to advance precision medicine strategies. [ABSTRACT FROM AUTHOR]

Periodontitis is a chronic inflammatory disease affecting teeth, periodontal ligament and alveolar bone. Current treatment options include surgery or oral antibiotics. Oral dosage forms shows systemic side effects due to frequent dosing and it failed to reach the therapeutic concentration in the periodontal cavity. In this work, a novel in situ gel loaded with azithromycin laden lipid liquid-crystalline nanoparticles (cubosomes) was formulated for effective treatment of periodontitis. Cubosomes were prepared using DL-α-monoolein (MO) and Pluronic®F-127, and characterized for size, zeta potential, shape, and entrapment efficacy. In situ gel laden cubosomes were evaluated for pH, drug content, viscosity, syringeability, mucoadhesive strength, texture profile, gelation temperature, gel strength, in vitro release profile, antimicrobial activity and in vivo efficacy in rat model. Cubosomal size (137–450 nm) and entrapment efficacy (74–88%) increases with increase in the level of MO. The in situ gel-cubosomal batches showed sufficient viscosity (878–956 cp), syringeability (125–150N), mucoadhesive strength (25.7–26.2 dyne/cm2), gelation temperature (34.3–35.3oC), gel strength (45–51 s), and texture profile for periodontal application. The in vitro release profiles showed sustain azithromycin release for 24h from the in situ gel-cubosomal gels compared to 4h from the marketed azithromycin gel. The in vivo studies (alveolar bone loss and histopathology) in rat model confirmed the efficacy of in situ gel to treat periodontitis at low frequency of dosing compared to marketed gel. In conclusion, the study demonstrated the potential of cubosomes to sustain the release of azithromycin from in situ gelling system for effective treatment of periodontitis. Graphical Abstract [ABSTRACT FROM AUTHOR]

People with comorbid conditions are at increased risk of developing severe/fatal coronavirus disease 2019 (COVID-19). We aimed to investigate the relationship between lipid levels and mortality in patients hospitalized for COVID-19 infection. In this retrospective study, we collected the details of 5274 COVID-19 patients who were diagnosed using the polymerase chain reaction and/or computed tomography and were hospitalized between March and November 2020. Patients (n = 4118) whose blood lipid levels were checked within the first 24 h after hospitalization were included in the study. Multivariable cox proportional hazards regression was used to assess the relationship between lipid variables such as low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TG) and death. There was a statistically significant association between LDL-C, HDL-C, and TG levels and the risk of death (P =.002, <.001, and.035, respectively). Low and high LDL-C, low HDL-C, and high TG levels were negatively associated with COVID-19-related mortality. Blood lipid levels may be useful predictors of mortality in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: This study aimed to describe the efficacy of veno-arterial extracorporeal life support (VA-ECLS) through early lactate clearance and pH restoration and assess the potential association with 30-day survival following hospital discharge. Methods: Data of patients receiving VA-ECLS for at least 24 h were retrospectively compiled. Blood lactate levels, liver enzymes, and kidney parameters prior to VA-ECLS initiation and at 2, 8, 14, 20, and 26 h of support had been recorded as part of clinical care. The primary outcome was 30-day survival. Results: Of 77 patients who underwent VA-ECLS for refractory cardiogenic shock, 44.2% survived. For all non-survivors, ECLS was initiated after eight hours (p =.008). Blood pH was significantly higher in survivors compared to non-survivors at all time points except for pre-ECLS. Lactate levels were significantly lower in survivors (median range 1.95-4.70 vs 2.90-6.70 mmol/L for survivors vs non-survivors, respectively). Univariate and multivariate analyses indicated that blood pH at 24 h (OR 0.045, 95% CI: 0.005-0.448 for pH <7.35, p =.045) and lactate concentration pre-ECLS (OR 0.743, 95% CI: 0.590-0.936, p =.012) were reliable predictors for 30-day survival. Further, ischemic cardiogenic shock as ECLS indication showed 36.2% less lactate clearance compared to patients with other indications such as arrhythmia, postcardiotomy, and ECPR. Conclusion: ECLS showed to be an effective treatment in reducing blood lactate levels in patients suffering from refractory cardiogenic shock in which the outcome is influenced by the initial lactate level and pH in the early phase of the intervention. [ABSTRACT FROM AUTHOR]

The non-vesicular transport of lipids between organelles mediated by lipid transport proteins (LTPs) is a key determinant of organelle biogenesis and function. Despite performing a vital function in organelle homeostasis, none of the LTP-encoding genes identified so far are truly essential, even in the simple genome of yeast, suggesting widespread redundancy. In line with this fact, it has been found that a number of LTPs have overlapping functions, making it challenging to assign unique roles for an individual LTP in lipid distribution. In our genetic screens under stringent conditions in which the distinct function of an LTP might become essential, we stumbled upon Csf1, a highly conserved protein with a Chorein-N motif found in other lipid transporters and unraveled a new function for Csf1 in lipid remodeling and homeoviscous adaptation of the lipidome. Here, we further speculate on the potential mechanisms of how the putative function of Csf1 in lipid transport could be intimately connected to its role in lipid remodeling across organelles. [ABSTRACT FROM AUTHOR]

Oral lichen planus is a chronic non-infectious mucosal inflammatory disease caused by an imbalance between reactive oxygen species homeostasis and antioxidant defense systems. Notably, excessive oxidative stress products result in related autoimmune reactions. Further, it activates signaling pathways related to the development of oral lichen planus, as evidenced by the detection of damage to deoxyribonucleic acid, protein, and lipid. Thus, the mechanisms of reactive oxygen species-mediated oxidative stress in the pathogenesis of oral lichen planus are numerous and complex. In this review, we first introduce oxidative stress and oxidative products. Then, we summarize the role and possible mechanisms of reactive oxygen species-mediated oxidative stress in the pathogenesis of oral lichen planus and present a clinical correlation between oxidative stress and oral lichen planus. Finally, we discuss the current challenges and future perspectives. [ABSTRACT FROM AUTHOR]

Objectives: Low cholesterol has been linked with violent and suicidal behaviour in people with schizophrenia. This association, if consistently present, may be a promising biological marker that could assist clinicians in decision making regarding risk and treatment. We conducted a systematic review to assess whether there is a reliable association between lipid profile (total cholesterol, high- and low-density lipoprotein cholesterol, and triglycerides) and aggression, self-harm or suicide in people with schizophrenia, and whether effects are similar in males and females. Method: Relevant databases were searched to identify primary research studies (up to November 2020) that (1) involved adults (some samples also included 16- to 18-year olds) with a confirmed diagnosis of schizophrenia, schizoaffective disorder or psychosis; and (2) included a standardised assessment of verbal aggression, physical aggression against objects, physical aggression against self (including suicide) or others. The search yielded 23 studies eligible for inclusion following a quality appraisal. Results: Suicidality was the most commonly assessed subtype of aggression (20 studies). For suicidality, about half the studies, including the study with the largest sample size, found a link with total cholesterol. An association between low total cholesterol and violence towards others was found in six of nine studies that investigated this. The evidence for a link with violence was the strongest for total cholesterol, followed by low-density lipoprotein cholesterol and high-density lipoprotein cholesterol, and the weakest for triglycerides. Only a few studies investigated sex differences and yielded mixed evidence. Studies focussed on self-harm as well as involving females in forensic settings were lacking. Conclusion: There is encouraging evidence of an association between low total cholesterol and aggression towards others as well as suicidality in schizophrenia. Future studies should systematically explore this association in people with schizophrenia who have a significant history of violence, suicidality and self-harm, both inpatients and community, and also investigate underlying mechanisms. [ABSTRACT FROM AUTHOR]

Introduction: Overt and subclinical hypothyroidism are mostly associated with dyslipidemia, an essential cardiovascular risk factor. Recently, thyroid stimulating hormone (TSH) was identified to have a direct role on lipid metabolism via increased expression of hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 plays a crucial role in lipid metabolism via regulating LDL-C levels. Thus, we aimed to evaluate circulating PCSK9 levels and to assess its relationship with serum TSH and lipids in newly diagnosed patients had overt and subclinical hypothyroidism. Methods: In our study, we enrolled 60 newly diagnosed untreated patients with overt and subclinical hypothyroidism and 30 euthyroid subjects served as the control group. Serum TSH, FT4, FT3, lipid profile and circulating PCSK9 levels using ELISA kits were measured in all subjects. Our data were summarized using mean ± SD or median and interquartile range. Correlations between PCSK9 expression levels and different variables were done using Spearman correlation coefficient. Results: Circulating PCSK9 median levels were significantly increased in patients had overt and subclinical hypothyroidism (12.45 ng/ml, 7.50 ng/ml respectively) compared to the control group (3.30 ng/ml) (P <.001). Circulating PCSK9 levels significantly correlated positively with TSH, total cholesterol, triglycerides, and BMI, and negatively correlated with FT4 and FT3 among all studied subjects. Using multivariate regression analysis TSH was the only significant independent predictor of circulating PCSK9 (P <.001). Conclusion: Our results supports the new implication of TSH in lipid metabolism via the significant association with PCSK9. Whether this relationship between TSH and PCSK9 is a cause or just an association needs further evaluation. [ABSTRACT FROM AUTHOR]

Background: Physical exercises are the first step of therapy for people with non-alcoholic fatty liver disease (NAFLD). Objective: The purpose of this meta-analysis is to evaluate the efficacy of aerobic exercise training with or without diet to ameliorate liver function, insulin resistance, and lipids in adults. Data sources: We searched relevant databases up to 10 June 2021 for conducting a systematic review and meta-analysis of controlled trials lasting 4 or more weeks that investigated the effects of aerobic exercise alone or accompanied by diet on change in liver enzymes, intrahepatic fat (IHF), insulin resistance, and lipids. Results: Sixteen studies including 2255 participants were included. There was a significant pooled weighted mean differences (MD) for the comparison between aerobic exercise versus control in alanine aminotransferase (ALT; p = 0.003), aspartate aminotransferase (AST; p = 0.006), IHF (p = 0.0004), body mass (p = 0.0003), and body mass index (p = 0.004). Moreover, there was a significant pooled MD for the comparison between aerobic exercise plus diet versus control in ALT (p < 0.0001), AST (p = 0.01), IHF (p = 0.02), GGT (p < 0.00001), insulin (p < 0.0001), HOMA-IR (p < 0.00001), body mass (p < 0.0001), and BMI (p = 0.01). Conclusion: Our findings demonstrate a role for aerobic exercise with and without diet protocol as a therapeutic purpose, and suggest that evaluation of aerobic training levels and aerobic training prescription plus diet should be routine in NAFLD. [ABSTRACT FROM AUTHOR]

Objective: To compare the effects of resistance and aerobic training (RT and AT) on spexin (SPX), appetite, lipid accumulation product (LAP), visceral adiposity index (VAI), and body composition in type 2 diabetes mellitus (T2DM) patients. Materials and Methods: Thirty-six T2DM men were randomized to receive RT (n = 12), AT (n = 12), or to act as a non-exercise control (CON, n = 12) 3 days a week for 12 weeks. Results: SPX was increased after both RT and AT (66.2% and 46.5%, respectively). VAI, LAP, and homeostasis model assessment-insulin resistance (HOMA-IR) were reduced in both groups, while quantitative insulin sensitivity check index (Quicki) and McAuley's indexes were increased following both interventions. However, the increases of both hunger and PFC in the RT group were greater than those of the AT. Moreover, the improvement of upper-body strength (41% vs. 10.3%) and lower-body strength (42.2% vs. 20.5%) in the RT group was greater than those of the AT. Conclusion: Our investigation shows that regardless of the modes of the regimen, a 12-week exercise intervention with RT and AT can effectively induce a significant improvement in SPX levels, appetite, LAP, VAI, and body composition in adults with T2DM. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of walking, independent of diet and weight-loss, on lipids and lipoproteins in women with overweight and obesity.Data Source: Academic Search Complete, Alternative Health Watch, Global Health, Health Source, CINAHL, MEDLINE, EMBASE, SportDiscus, and ProQuest.Study Inclusion and Exclusion Criteria: (1) experiment-control design; (2) women with overweight or obesity; (3) walking as the experiment's independent variable; (4) four or more weeks; and (5) pre- to post-assessment of lipids and/or lipoproteins. Excluded studies reported use of lipid-lowering medication, diet or other modes of physical activity, and alternative interventions as the control.Data Extraction: Data extraction and study quality were completed by the first 2 authors using the Cochrane review protocol and risk of bias assessment.Data Synthesis: Raw mean difference between the experiment and control groups using a random effects model.Results: Meta-analyses of 21 interventions (N = 1129) demonstrated exclusive walking improves total cholesterol (raw mean difference = 6.67 mg/dL, P = .04) and low-density lipoproteins (raw mean difference = 7.38 mg/dL, P = .04). Greater improvement in total cholesterol, triglycerides, high-density lipoproteins, and low-density lipoproteins existed in women with obesity.Conclusions: Exclusive walking aids in normalizing total cholesterol and LDLs in women with overweight and obesity. Exclusive walking can be used as a non-pharmacologic therapy, which may have positive clinical outcomes for individuals who especially struggle with diet and weight-reduction. [ABSTRACT FROM AUTHOR]

African American women are more likely to experience preterm birth (<37 completed weeks gestation) compared with White women. African American women are also more likely to live in neighborhoods characterized as disadvantaged (i.e., exhibiting higher rates of vacant housing, poorer property conditions, and more litter and crime) and to experience racial discrimination compared with White women. These chronic stressors have been related to preterm birth (PTB) among African American women. This review focuses on potential stress-related pathways by which neighborhood disadvantage and racial discrimination increase the risk for PTB among African American women. Specifically, we propose cortisol, systemic inflammation, proteome and lipidome profiles, and telomere shortening as potential mediators linking these social determinants of health with PTB among African American women. Examination of these factors and the signaling pathways they contribute to will increase our knowledge of the effects of social determinants of health on PTB for African American women. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Overt and subclinical hypothyroidism are mostly associated with dyslipidemia, an essential cardiovascular risk factor. Recently, thyroid stimulating hormone (TSH) was identified to have a direct role on lipid metabolism via increased expression of hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 plays a crucial role in lipid metabolism via regulating LDL-C levels. Thus, we aimed to evaluate circulating PCSK9 levels and to assess its relationship with serum TSH and lipids in newly diagnosed patients had overt and subclinical hypothyroidism. METHODS: In our study, we enrolled 60 newly diagnosed untreated patients with overt and subclinical hypothyroidism and 30 euthyroid subjects served as the control group. Serum TSH, FT4, FT3, lipid profile and circulating PCSK9 levels using ELISA kits were measured in all subjects. Our data were summarized using mean ± SD or median and interquartile range. Correlations between PCSK9 expression levels and different variables were done using Spearman correlation coefficient. RESULTS: Circulating PCSK9 median levels were significantly increased in patients had overt and subclinical hypothyroidism (12.45 ng/ml, 7.50 ng/ml respectively) compared to the control group (3.30 ng/ml) (P < .001). Circulating PCSK9 levels significantly correlated positively with TSH, total cholesterol, triglycerides, and BMI, and negatively correlated with FT4 and FT3 among all studied subjects. Using multivariate regression analysis TSH was the only significant independent predictor of circulating PCSK9 (P < .001). CONCLUSION: Our results supports the new implication of TSH in lipid metabolism via the significant association with PCSK9. Whether this relationship between TSH and PCSK9 is a cause or just an association needs further evaluation. [ABSTRACT FROM AUTHOR]

In this research, magnetic nanostructured lipid carriers (Mag-NLCs) were synthesized for curcumin (CUR) delivery. NLCs are drug-delivery systems prepared by mixing solid and liquid (oil) lipids. For preparation of NLCs, cetylpalmitate was selected as solid lipid and fish oil as liquid lipid. CUR-Mag-NLCs were prepared using high-pressure homogenization technique and were characterized by methods including X-ray diffraction (XRD), transmission electron microscopy (TEM), vibrating sample magnetometer (VSM), and dynamic light scattering (DLS). The CUR-Mag-NLCs were developed as a particle with a size of 140 ± 3.6 nm, a polydispersity index of 0.196, and a zeta potential of −22.6 mV. VSM analysis showed that the CUR-Mag-NLCs have excellent magnetic properties. Release rate of the drug was higher at 42 °C than 37 °C, indicating that release of the synthesized nanoparticles is temperature-dependent. Evaluation of mitochondrial toxicity was done using the isolated rats liver mitochondria including glutathione (GSH), malondialdehyde (MDA), and the ferric- reducing ability of plasma (FRAP) assays to study biosafety of the CUR-Mag-NLCs. Results of In vitro study on the isolated mitochondria revealed that both CUR-Mag-NLCs and curcumin have no specific mitochondrial toxicity. [ABSTRACT FROM AUTHOR]

Background: Diabetes nephropathy (DN) is a serious diabetic problem that may progress to renal failure. The root of Curcuma longa L., often known as turmeric, provides various health benefits. Bisacurone is a bioactive terpenoid found in small amounts in turmeric that possesses anti-inflammatory and antioxidant properties. The present study focuses on the potential protective effects of bisacurone against DN via reducing renal inflammation, oxidative stress, and apoptosis. Methods: Type 2 diabetes was created in rats by feeding them a high-fat/high-sugar diet for 8 weeks, followed by a low dose of streptozotocin and Bisacurone (50 and 100 μg/kg bisacurone) given for 4 weeks. Results: In diabetic rats, bisacurone reduced hyperglycemia, protected against body weight (BW) loss, lowered renal markers, reduced lipid profile alterations and avoided histological abnormalities. Bisacurone treatment reduced oxidative stress by decreasing malondialdehyde (MDA) levels while enhancing antioxidant defenses through superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) levels. Furthermore, bisacurone treatment activated the renal Nrf2/Keap1 signaling pathway but attenuated the high levels of NFκB p65, TNF-α, IL-1β, IL-6, Cox2, and iNOS. Bisacurone also reduced Bax, caspase-3, caspase-9 and cytochrome c but increased Bcl-2 in the kidneys of diabetic rats. Conclusion: In the present study, bisacurone reduces DN by reducing hyperglycemia, oxidative stress, inflammation, and apoptosis, while also increasing Nrf2/HO-1 signaling. [ABSTRACT FROM AUTHOR]

Background: Human dental pulp stem cells (hDPSCs) possess mesenchymal stem cell properties, originating from migrating neural crest cells. hDPSCs have received extensive attention in the field of tissue engineering and regenerative medicine due to their accessibility and ability to differentiate in several cell phenotypes. In this study, we cultured hDPSCs with Y-27632 to observe their biological behaviors changes. Methods: The hDPSCs were separately cultured with Y-27632 (0, 0.156, 0.312, 0.625, 1.25, 2.50, 5, 10, 20, 40 μ m) for 24, 48, 72 h to select the suitable concentration and time using CCK-8. Then, the hDPSCs were cultured with 2.50 μ m Y-27632 for 48 h to analyzed the biological behaviors changes by 5-Ethynyl-2′-deoxyuridine (EdU), plate cloning, transwell, scratch, and Annexin V FITC/PI assays, separately. Additionally, osteogenic calcium nodules and lipid droplets were analyzed using alizarin red staining and oil red O staining, respectively. qRT-PCR was used to analyze the expression of osteogenesis, adipogenesis, stemness maintenance, and inflammation related genes. Results: The hDPSCs proliferation was significantly enhanced after cultured with 2.50 μ m Y-27632 for 48 h, but there was no significant difference in migration and apoptosis. Observation of alkaline phosphatase (ALP) activity, osteogenic and adipogenic differentiation abilities of hDPSCs, Y-27632 treatment clearly decreased the ALP activity and osteogenic differentiation ability, increased the adipogenic differentiation ability. Furthermore, Y-27632 decreased the CD73, CD90, CD105, CD166, TLR4, and NF-κB p65 genes expression, but increased the IL-8 gene expression. Conclusions: The biological behaviors of hDPSCs could be changed when they cultured with Y-27632. [ABSTRACT FROM AUTHOR]

Purpose: The current investigation was carried out to evaluate the efficacy of myricetin in ethanol-induced liver toxicity in Wistar rats. Research Design: Twenty-four rats were randomly divided into four groups with six animals per group. Group-I animals were administered with vehicle (distilled water), Group II, III, and IV were treated orally with sequential (per week) increase in the dose of ethanol (5, 8, 10, and 12 g/kg b wt per week in each group) for 28 days. Myricetin was treated orally to Group-III and IV animals at the respective doses of 25 mg/kg b wt. and 50 mg/kg b wt. Results: Our results showed that myricetin prevented hepatotoxicity by modulating the production of free radicals, ethanol metabolizing enzymes, and inflammatory markers in vivo. Myricetin also helped maintain lipid membrane integrity, oxidant-antioxidant status, and histoarchitecture. Ethanol administration caused elevation in XO, ADH, and CYP2E1 in hepatic tissue, which significantly normalized with myricetin administration. After ethanol administration, there was a steep increase in the hepatotoxicity biomarkers, including ALT, MDA, and AST. The level of cytotoxicity marker LDH also increased after ethanol administration; myricetin administration decreased the level of all these markers. Moreover, myricetin treatment also reduced ethanol-induced inflammatory markers such as NF-κB and IL-6. Conclusion: Findings from the current study demonstrate that myricetin administration prevents alcohol-induced hepatic injury by influencing the metabolism of ethanol, inhibiting oxidative stress, maintaining lipid profile, and suppressing inflammatory markers. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus is a progressive polygenic disorder requiring a multi-targeted therapeutic approach. A polyherbal formula (PHF) comprised of four traditional herbs known for their anti-diabetic, anti-oxidant, and hepatoprotective activities were used in this study. Objectives: The purpose of this research was to find out the plausible mechanisms underlying the synergistic effects of PHF in an experimental setting of diabetes mellitus. Materials and Methods: PHF was evaluated for the presence of residual toxins, acute oral toxicity, and its effects on carbohydrate digestive enzymes. PHF (100, 200, and 300 mg/kg/p. o., respectively) was used to treat streptozotocin-induced diabetic rats for 12 weeks followed by glycemic, histopathological, biochemical, and ultrastructural changes measurement. mRNA levels of AMPK, insulin receptor substrate (IRS), phosphoinositide-3-phosphate kinase (PI3K), Akt, and glucose transporter 2 (GLUT2) were measured using real-time polymerase chain reaction. Results: In PHF, the residual toxins were absent. PHF inhibited the α-amylase (IC50 152.2 ± 9.3 μg/mL), and α-glucosidase (IC50 103.0 ± 0.81 μg/mL) activities in-vitro. Further, up to a dose of 2000 mg/kg, PHF showed no signs of mortality. PHF treatment significantly maintained the glycemic state, antioxidant status, lipid profile, hepatic-architecture, and ultrastructural alterations in diabetic rats. Similarly, diabetic rats showed detrimental effects on the mRNA level of AMPK and IRS-PI3K-Akt-GLUT2 signaling which were attenuated by PHF treatment. Immunohistochemical analysis also revealed an improvement in p-Akt expression after PHF treatment. Conclusion: In streptozotocin-induced diabetic rats, PHF improves glucose and lipid metabolism by attenuating hyperglycemia, hyperinsulinemia, dyslipidemia, insulin resistance, oxidative stress, inflammation, and deterioration of hepatic architecture possibly through AMPK mediated improvement in hepatic IRS-PI3K-Akt-GLUT2 signaling pathway. [ABSTRACT FROM AUTHOR]