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Background: Steatotic liver disease (SLD) prevalence is rising worldwide, linked to insulin resistance and obesity. SLD prevalence can surpass 10% even among those with normal weight. In Lao People's Democratic Republic (Lao PDR), where Opisthorchis viverrini (OV) trematode infection and type 2 diabetes mellitus (T2DM) are common, infection related liver morbidity such as cholangiocarcinoma (CCA) is high, but data on SLD prevalence is lacking. The objective of this study was to estimate the prevalence and explore determinants of SLD in rural southern Lao PDR for lean and non-lean populations. Method: A cross-sectional community-based study assessed SLD prevalence using abdominal ultrasonography (US). Factors investigated for association with SLD were identified by interview, serological tests (Hepatitis B surface antigen (HBsAg); lipids and HbA1c), anthropometrical measurements, and parasitological assessments (OV infection). Uni- and multivariable logistic regression analyses with SLD as endpoint were conducted separately for lean (body mass index (BMI) <23.0kg/m²) and non-lean (BMI ≥ 23.0kg/m²) participants. Result: 2,826 participants were included. SLD prevalence was 27.1% (95% confidence interval (95% CI) 24.0%-30.4%), higher among non-lean (39.8%) than lean individuals (17.4%). Lean individuals with OV infection had a statistically significant association with lower odds of SLD (adjusted odds ratio (aOR) 0.49, 95% CI 0.33-0.73). T2DM showed a significant positive association with SLD in both lean (aOR 3.58, 95% CI 2.28-5.63) and non-lean individuals (aOR 3.31, 95% CI 2.31-4.74) while dyslipidemia was significantly associated only in the non-lean group (aOR 1.83, 95% CI 1.09-3.07). Females participants exhibited elevated odds of SLD in both lean (aOR 1.43, 95% CI 1.02-2.01) and non-lean SLD (aOR 1.50, 95% CI 1.12-2.01). Conclusion: SLD prevalence is notably high among Laotian adults in rural areas, particularly in females and in non-lean individuals. Lean individuals with OV infection exhibited lower SLD prevalence. SLD was more prevalent in individuals with T2DM, independent of BMI. SLD adds to the burden of infection-related liver morbidity in Lao PDR. [ABSTRACT FROM AUTHOR]

Background: Abdominal aortic aneurysm (AAA) is highly lethal upon onset of acute aortic diseases (AAD) or rupture. Dyslipidaemia and hyperuricaemia are important risk factors for the development of AAA and AAD as well as aortic disease-related death. The aim of this study was to explore whether uric acid (UA) to high-density lipoprotein cholesterol (HDL-C) ratio (UHR) can be used as an independent predictor of the presence of AAA or AAD. Methods: Three hundred subjects, including 100 AAA patients (AAA group), 100 AAD patients (AAD group) and 100 controls (CON group), were recruited in this study. UHR and other serum samples were obtained upon the patients' admission before any medical treatment. The optimal cut-off points of UHR were determined using receiver operating characteristic (ROC) curve analysis. Results: The UHR in AAA group was significantly higher than that in CON group, but there was no significant difference between AAD group and CON group. The optimal cut-off point of UHR for AAA was 7.78 (sensitivity 84.7%, specificity 62.4%, and AUC 0.811; p < 0.001), and UHR (OR: 1.122, 95%CI: 1.064-1.184; p < 0.001) was found to be an independent factor for predicting AAA after adjusting for traditional AAA risk factor. Conclusion: UHR can be widely used in clinical practice as an auxiliary tool for screening AAA. The optimal cut-off point for UHR to AAA was determined for the first time in Chinese subjects. [ABSTRACT FROM AUTHOR]

Lipid testing for atherosclerotic cardiovascular disease (ASCVD) risk is often performed every 4–6 years, but we hypothesized that the optimum time interval may vary depending on baseline risk. Using lipid values and other risk factors from the National Health and Nutrition Examination Survey (NHANES) (n = 9,704), we calculated a 10-year risk score with the pooled-cohort equations. Future risk scores were predicted by increasing age and projecting systolic blood pressure (SBP) and lipid changes, using the mean-percentile age group change in NHANES for SBP (n = 17,329) and the Lifelines Cohort study for lipids (n = 133,540). The crossing of high and intermediate-risk thresholds were calculated by time to determine optimum intervals for lipid testing. Time to crossing risk thresholds depends on baseline risk, but the mean increase in the risk score plateaus at 1% per year for those with a baseline 10-year risk greater than 15%. Based on these findings, we recommend the following maximum time intervals for lipid testing: baseline risk < 15%: 5-years, 16%: 4-years, 17%: 3-years, 18%: 2-years, and 19%: ≤1-year. Testing patients for lipids who have a higher baseline risk more often could identify high-risk patients sooner, allowing for earlier and more effective therapeutic intervention. [ABSTRACT FROM AUTHOR]

It is well known, that the inflammatory process that characterizes acute pancreatitis (AP) can lead to both pancreatic damage and systemic inflammatory response syndrome (SIRS). During the last 20 years, there has been a growing incidence of episodes of acute pancreatitis associated with hypertriglyceridaemia (HTAP). This review provides an overview of triglyceride metabolism and the potential mechanisms that may contribute to developing or exacerbating HTAP. The article comprehensively discusses the various pathological roles of free fatty acid, inflammatory response mechanisms, the involvement of microcirculation, serum calcium overload, oxidative stress and the endoplasmic reticulum, genetic polymorphism, and gut microbiota, which are known to trigger or escalate this condition. Future perspectives on HTAP appear promising, with ongoing research focused on developing more specific and effective treatment strategies. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine the effect of tripterygium glycosides (TGs) on regulating abnormal lipid deposition in nephrotic syndrome (NS) rats. Sprague-Dawley (SD) rats were injected with 6 mg/kg doxorubicin to construct nephrotic syndrome models (n = 6 per group), and then administered with TGs (10 mg/kg·d−1), prednisone (6.3 mg/kg·d−1), or pure water for 5 weeks. Biomedical indexes, such as urine protein/creatinine ratio (PCR), blood urea nitrogen (BUN), serum creatinine (Scr), serum albumin (SA), triglycerides (TG), total cholesterol (TC)were investigated to evaluate the renal injury of rats. H&E staining experiment was used to assess the pathological alterations. Oil Red O staining was used to assess the level of renal lipid deposition. Malondialdehyde (MDA) and glutathione (GSH) were measured to assess the extent of oxidative damage to the kidney. TUNEL staining was used to assess the status of apoptosis in the kidney. Western blot analysis was performed to examine the levels of relevant intracellular signaling molecules. After treatment with TGs, those tested biomedical indexes were significantly improved, and the extent of kidney tissue pathological changes and lipid deposition in the kidney was diminished. Treatment with TGs decreased renal oxidative damage and apoptosis. Regarding the molecular mechanism, TGs significantly increased the protein expression levels of Bcl-2 but decreased the levels of CD36, ADFP, Bax, and Cleaved caspase-3. TGs alleviates renal injury and lipid deposition induced by doxorubicin, suggesting that it may be a new strategy for reducing renal lipotoxicity in NS. [ABSTRACT FROM AUTHOR]

Peritoneal fibrosis caused by long-term peritoneal dialysis (PD) is the main reason why patients withdraw from PD treatment. Lipid accumulation in the peritoneum was shown to participate in fibrosis, and klotho is a molecule involved in lipid metabolism. GSK343 (enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitor) has been verified to inhibit epithelial mesenchymal transdifferentiation (EMT) and peritoneal fibrosis, but its related mechanism remains unclear. This study aimed to investigate whether lipid accumulation was involved in the effect of GSK343 and its related mechanism. First, the expression of EZH2, klotho and EMT indices in human peritoneal mesothelial cells (HMrSV5) incubated with high glucose (HG) levels was detected. After EZH2 was inhibited by GSK343, Western blot (WB), wound healing and Transwell assays were used to explore the effect of GSK343. EZH2 and klotho expression was also detected. Oil red O and Nile red staining and triglyceride (TG) detection kits were used to detect lipid accumulation. A rescue experiment with small interfering RNA specific for klotho (si-klotho) on the basis of GSK343 was also conducted to verify that GSK343 exerted its effect via klotho. In in vivo experiments, rats were administered GSK343, and the related index was assessed. In our study, we revealed that the expression of EZH2 was significantly upregulated and klotho was significantly downregulated in HMrSV5 cells induced by high glucose. With the aid of GSK343, we found that lipid deposition caused by HG was significantly decreased. In addition, EMT and fibrosis were also significantly alleviated. Moreover, GSK343 could also restore the downregulation of klotho. To further verify whether klotho mediated the effect of EZH2, a rescue experiment with si-klotho was also conducted. The results showed that si-klotho could counteract the protective effect of GSK343 on high glucose-induced lipid accumulation and fibrosis. In vivo experiments also revealed that GSK343 could relieve peritoneal fibrosis, lipid deposition and EMT by mitigating EZH2 and restoring klotho expression. Combining these findings, we found that EZH2 regulated lipid deposition, peritoneal fibrosis, and EMT mediated by klotho. To our knowledge, this is the first study to demonstrate the effect of the EZH2-klotho interaction on peritoneal fibrosis. Hence, EZH2 and klotho could act as potential targets for the treatment of peritoneal fibrosis. [ABSTRACT FROM AUTHOR]

This work aimed to investigate the effect of energy nature (lipids vs. carbohydrates) on enteric methane emission (eCH4) and performance in dairy cows fed grass silage-based diets. Eight multiparous Holstein cows were used in a 4 × 4 Latin square design, with 4 experimental periods of 28 days each. Cows were fed with 4 iso-energetic diets based on grass silage and supplemented with different levels of rapeseed oil (RO) (0, 1.5, 3.0, 4.5% of dietary dry matter (DM), Control, RO-low, RO-medium, RO-high diets, respectively) in substitution of starch from concentrate. Dairy performance, total-tract digestibility, and rumen parameters were measured when animals were in individual respiration chambers for quantifying eCH4. Intake of DM decreased with RO-high compared to other diets. Methane emissions were lowered similarly with all diets containing RO compared to Control (on average, -19% in g/d, −13% in g/kg DMI, −21% in g/kg milk). Ruminal propionate proportion was higher, whereas that of butyrate was lower with RO-high compared to the other diets. Milk yield was higher with RO-low and RO-medium, and was lower for RO-high compared to Control. Milk C16:0 concentration was lower, and C18:1c9, C18:1t11, and other rumen biohydrogenation intermediate concentrations were higher with diets containing RO compared to Control. The shift from the C18:1t11 to C18:1t10 biohydrogenation pathway is in agreement with the milk fat depression observed with RO-medium and RO-high. The inclusion of RO at 1.5% was the best compromise between eCH4, feed efficiency, and milk nutritional quality in cows fed grass silage-based diets. Energy substitution of carbohydrate (mainly starch) by rapeseed oil reduced methane emissions in dairy cows fed grass silage-based diets (up to –23% in g/d) Rapeseed oil content above 3% induced milk fat depression and impaired milk fatty acid profile The inclusion of 1.5% rapeseed oil was the best compromise to reduce methanogenesis (–15% in g/d) and improve dairy performance and milk nutritional quality [ABSTRACT FROM AUTHOR]

Functionalized drug delivery systems have been investigated to improve the targetability and intracellular translocation of therapeutic drugs. We developed high functionality and quality lipids that met unique requirements, focusing on the quality of functional lipids for the preparation of targeted nanoparticles using microfluidic devices. While searching for a lipid with high solubility and dispersibility in solvents, which is one of the requirements, we noted that KK-(EK)4-lipid imparts nonspecific cellular association to polyethylene glycol (PEG)-modified (PEGylated) liposomes, such as cell-penetrating peptides (CPPs). We investigated whether KK-(EK)4-lipid, which has a near-neutral charge, is a novel CPP-modified lipid that enhances the intracellular translocation of nanoparticles. However, the cellular association mechanism of KK-(EK)4-lipid is unknown. Therefore, we synthesized (EK)n-lipid derivatives based on the sequence of KK-(EK)4-lipid and determined the sequence sites involved in cellular association. In addition, KK-(EK)4-lipid was applied to extracellular vesicles (EVs) and mRNA encapsulated lipid nanoparticles (mRNA-LNPs). KK-(EK)4-lipid-modified EVs and mRNA-LNPs showed higher cellular association and in vitro protein expression, respectively, compared to unmodified ones. We elucidated KK-(EK)4-lipid to have potential for applicability in the intracellular delivery of liposomes, EVs, and mRNA-LNPs. [ABSTRACT FROM AUTHOR]

Oral squamous cell carcinoma (OSCC) is the most common epithelial tumor of the oral cavity. Gingival tumors, a unique type of OSCC, account for 10% of these malignant tumors. The antineoplastic properties of statins, including pitavastatin (PV), and the essential oil of the Pinus densiflora leaf (Pd oil) have been adequately reported. The goal of this investigation was to develop nanostructured lipid carriers (NLCs) containing PV combined with Pd oil and to determine their cytotoxicity against the cell line of human gingival fibroblasts (HGF-1). A central composite quadratic design was adopted to optimize the nanocarriers. The particle size and stability index of the nano-formulations were measured to evaluate various characteristics. TEM analysis, the entrapment efficiency, dissolution efficiency, and the cytotoxic efficiency of the optimized PV-loaded nanostructured lipid carrier drug delivery system (PV-Pd-NLCs) were evaluated. Then, the optimal PV-Pd-NLCs was incorporated into a Carbopol 940® gel base and tested for its rheological features and its properties of release and cell viability. The optimized NLCs had a particle size of 98 nm and a stability index of 89%. The gel containing optimum PV-Pd-NLCs had reasonable dissolution efficiency and acceptable rheological behavior and acquired the best cytotoxic activity against HGF-1 cell line among all the formulations developed for the study. The in vitro cell viability studies revealed a synergistic effect between PV and Pd oil in the treatment of gingival cancer. These findings illustrated that the gel containing PV-Pd-NLCs could be beneficial in the local treatment of gingival cancer. [ABSTRACT FROM AUTHOR]

Amphotericin B (AmB) is regarded as a first-line therapy against life-threatening invasive fungal infections. Due to its poor oral bioavailability, AmB is restricted to intravenous administration in clinical practice. As science continues to move forward, two lipid-based formulations are successfully developed for oral AmB administration, currently undergoing phase I clinical trials. Encouragingly, lipid-AmB conjugates with emulsions also exhibit a better bioavailability, which may be another strategy to design oral AmB formulation in clinical practice. Thus, this review mainly focused on the two lipid-based formulations in clinical trials, and discussed the potential perspectives of AmB-lipid conjugation-loaded nanocochleates and emulsions. [ABSTRACT FROM AUTHOR]

Gouty arthritis (GA) is a characteristically inflammatory disease often associated with lipid metabolism disorder. Huangqin Qingrechubi capsule (HQC) has been used for the treatment of GA. To explore the mechanism of HQC in the treatment of GA. A total of 30 GA patients (GA group) and 30 healthy subjects [normal control (NC) group] were recruited. The GA group was treated with HQC (3.6 g/d) for 10 days. Lipid metabolism and inflammation indexes were detected. Five herbal names of HQC, or 'gouty arthritis', 'hyperlipidemia' and 'inflammation' were used as key words to search related databases for network pharmacological analysis. Subsequently, GA-fibroblast-like synoviocytes (FLSs) were stimulated with GA-peripheral blood mononuclear cells (PBMCs) (3:1) and treated with HQC drug-containing serum (20%). RT-qPCR, Western blot, and ELISA were conducted to further explore the mechanism of HQC in improving GA. In clinical observation, HQC decreased the expression of lncRNA H19 and IL-1β, and increased the expression of adiponectin (APN) and IL-4 in the GA group (about half). Through network pharmacology, the PI3K/AKT signaling pathway was identified. Cell experiments showed that HQC treatment reduced the viability of GA-FLSs (49.61%), up-regulated the expression of IL-4 (155.18%), IL-10 (165.13%), and APN (31.24%), and down-regulated the expression of lncRNA H19 (33.70%), IL-1β (64.70%), TNF-α (78.32%), p-PI3K (48.80%), and p-AKT (53.48%). HQC improved lipid metabolism disorder and inflammatory response of GA by regulating the lncRNA H19/APN/PI3K/AKT. Maintaining the stability of lipid metabolism may be an effective way to alleviate GA. [ABSTRACT FROM AUTHOR]

Cisplatin, as a first-line treatment for ovarian cancer, is associated with debilitating adverse effects, including nephrotoxic and haematotoxic effects. This study determines whether nanocurcumin, combined with cisplatin, would give additional benefit to kidney function and haematological parameters in rats with ovarian cancer. Twenty-five Wistar rats were divided into five untreated rats and 20-dimethylbenz(a)anthracene (DMBA)-induced ovarian cancer rats. The 20 ovarian cancer rats were divided into four treatment groups: vehicle, cisplatin, cisplatin-curcumin, and cisplatin-nanocurcumin. Cisplatin was given at the dose of 4 mg/kg BW once weekly, while curcumin or nanocurcumin was administered at 100 mg/kg BW daily for four weeks. At the end of treatment, we analysed kidney function, haematological parameters, and inflammatory and oxidative stress markers from plasma. Nanocurcumin alleviates the increase in kidney function markers and abnormalities in haematological indices in rats treated with cisplatin. Compared to cisplatin-treated rats, plasma urea levels decreased from 66.4 to 47.7 mg/dL, creatinine levels lowered from 0.87 to 0.82 mg/dL, and neutrophil gelatinase-associated lipocalin (NGAL) levels declined from 8.51 to 3.59 mIU/mg protein. Furthermore, the therapy increased glutathione activities (from 2.02 to 3.23 U/µL), reduced lipid peroxidation (from 0.54 to 0.45 nmol/mL), and decreased plasma TNF-α (from 270.6 to 217.8 pg/mL). Cisplatin with nanocurcumin in an ovarian cancer rat model may provide additional benefits as a preventive agent against renal impairment and cisplatin-induced haematological toxicity. However, further research is required to prove that using nanocurcumin for a more extended time would not affect its anticancer properties. [ABSTRACT FROM AUTHOR]

Previously, we found Alisma orientalis beverage (AOB), a classic traditional Chinese medicine (TCM) formulation, had the potential effect of treating atherosclerosis (AS). The underlying mechanism was still unclear. As an extention of our previous work, to investigate the underlying mechanism of action of AOB in the treatment for AS. Network pharmacology was conducted using SwissTargetPrediction, GeneCards, DrugBank, Metascape, etc., to construct component-target-pathway networks. In vivo, AS models were induced by a high-fat diet (HFD) for 8 consecutive weeks in APOE−/− mice. After the administration of AOB (3.8 g/kg, i.g.) for 8 weeks, we assessed the aortic plaque, four indicators of blood lipids, and expression of the PI3K/AKT/SREBP-1 pathway in liver. Network pharmacology showed that PI3K/AKT/SREBP-1 played a role in AOB's treatment for AS (PI3K: degree = 18; AKT: degree = 17). Moreover, we found that the arterial plaque area and four indicators of blood lipids were all significantly reversed by AOB treatment in APOE−/− mice fed with HFD (plaque area reduced by about 37.75%). In addition, phosphorylated expression of PI3K/AKT and expression of SREBP-1 were obviously increased in APOE−/− mice fed with HFD, which were all improved by AOB (PI3K: 51.6%; AKT: 23.6%; SREBP-1: 40.0%). AOB had therapeutic effects for AS by improving blood lipids and inhibition of the PI3K/AKT/SERBP-1 pathway in the liver. This study provides new ideas for the treatment of AS, as well as new evidence for the clinical application of AOB. [ABSTRACT FROM AUTHOR]

To explore hypertension management in primary healthcare (PHC). Structured interviews of randomly selected PHC centres (PHCCs) from December 2019 to January 2021. Seventy-six PHCCs in eight regions of Sweden. Staffing and organization of hypertension care. Methods of measuring blood pressure (BP), laboratory tests, registration of co-morbidities and lifestyle advice at diagnosis and follow-up. The management of hypertension varied among PHCCs. At diagnosis, most PHCCs (75%) used the sitting position at measurements, and only 13% routinely measured standing BP. One in three (33%) PHCCs never used home BP measurements and 25% only used manual measurements. The frequencies of laboratory analyses at diagnosis were similar in the PHCCs. At follow-up, fewer analyses were performed and the tests of lipids and microalbuminuria decreased from 95% to 45% (p < 0.001) and 61% to 43% (p = 0.001), respectively. Only one out of 76 PHCCs did not measure kidney function at routine follow-ups. Lifestyle, physical activity, food habits, smoking and alcohol use were assessed in ≥96% of patients at diagnosis. At follow-up, however, there were fewer assessments. Half of the PHCCs reported dedicated teams for hypertension, 82% of which were managed by nurses. There was a great inequality in the number of patients per tenured GP in the PHCCs (median 2500; range 1300–11300) patients. The management of hypertension varies in many respects between PHCCs in Sweden. This might lead to inequity in the care of patients with hypertension. Hypertension is mainly handled in primary healthcare (PHC), and this study shows important dissimilarities in organization and clinical management. Several variants in techniques and measurements of blood pressure were found between PHC centres. Lifestyle, clinical and laboratory assessments decreased at follow-ups compared to at diagnosis, specifically for lipids, microalbuminuria and electrocardiograms. Nearly half of the PHC centres reported that they had dedicated hypertension teams. [ABSTRACT FROM AUTHOR]

Despite highly active antiretroviral therapy (HAART) leading to a decline in human immunodeficiency virus (HIV)-induced morbidity and mortality, in recent years HAART has been implicated in abnormal lipid profiles, diabetes mellitus (DM) and predisposition of patients to cardiovascular disease (CVD). In this comparative study, the side effects of HAART as well as other lifestyle factors such as diet, exercise, alcohol and/or smoking were assessed, as well as family history of diabetes between HIV-infected and HIV-uninfected patients of African ancestry with DM. The study population consisted of 80 Black African diabetic patients (18–65 years old) stratified by HIV status (HIV-infected n = 40; HIV-uninfected n = 40). Anthropometric measurements (weight, height and BMI) and blood pressure (BP), as well as biochemical tests for glucose, cholesterol, high-density lipoproteins (HDL), low-density lipoproteins (LDL) and triglycerides were performed. The median BMI indicated overweight in the HIV-infected compared with the HIV-uninfected, which was congruent with obesity. Systolic BP was higher in the HIV-infected compared with the HIV-uninfected groups, at 138.15 and 134.75 mmHg (p = 0.1651), respectively. Glucose was high in both groups, confirming diabetes (p = 0.3900). Cholesterol was high (4.85 mmol/l) in the HIV-infected group while HDL was lower (0.95 mmol/l) in the HIV-uninfected group. Triglycerides were elevated in the HIV-uninfected (1.90 mmol/l) compared with the HIV-infected (1.61 mmol/l) (p = 0.7500) group. Despite HAART being documented as a contributor to DM and abnormal lipid profiles in the HIV-infected group, lifestyle factors such as diet also affect obesity phenotype in the uninfected group. Thus, irrespective of DM and/or HIV status, a lack of exercise, behavioural and lifestyle risk factors exacerbate abnormal lipid profiles. Notably, a family history of DM showed a strong susceptibility to its development. [ABSTRACT FROM AUTHOR]

During eukaryotic cell division, organelles are distributed between daughter cells through a dynamic process to ensure that cells can differentiate and perform their functions correctly. Uncovering the mode of lipid droplet (LD) distribution may help reveal the mechanism of membrane remodeling during cell division and lipid droplet function. Our results showed that LDs were equally distributed in both daughter cells during cytokinesis. Further experiments demonstrated that the key factor regulating the movement of LDs is the microtubule (MT)-resident protein KIF5B. Because the KIF5B structure lacks a hydrophilic region, we believe that there are proteins that mediate the interaction between LDs and KIF5B. Mass spectrometric detection of KIF5B-interacting proteins on the surface of LDs demonstrated that LDs were first wrapped by intermediate filaments forming a meshwork and then contacted with MTs to mediate lipid droplet movement during cytokinesis. Disruption of the homogeneous distribution of LDs may hinder cell proliferation and even lead to apoptosis. [ABSTRACT FROM AUTHOR]

To examine whether education level influences screening, monitoring, and treatment of hypercholesterolemia. Epidemiological cohort study. Department of Clinical Biochemistry, Copenhagen University Hospital Hvidovre. Cholesterol blood test results ordered by general practitioners in Greater Copenhagen were retrieved from 2000-2018. Using the International Standard Classification of Education classification, the population was categorized by length of education in three groups (basic education; up to 10 years, intermediate education; 11-12 years, advanced education; 13 years or more). The database comprised 13,019,486 blood sample results from 653,903 patients. Frequency of lipid measurement, prevalence of statin treatment, age and comorbidity at treatment initiation, total cholesterol threshold for statin treatment initiation, and achievement of treatment goal. The basic education group was measured more frequently (1.46% absolute percentage difference of total population measured [95% CI 0.86%–2.05%] in 2000 and 9.67% [95% CI 9.20%–10.15%] in 2018) over the period compared to the intermediate education group. The advanced education group was younger when receiving first statin prescription (1.87 years younger [95% CI 1.02–2.72] in 2000 and 1.06 years younger [95% CI 0.54–1.58 in 2018) compared to the intermediate education group. All education groups reached the treatment goals equally well when statin treatment was initiated. Higher education was associated with earlier statin prescription, although the higher educated group was monitored less frequently. There was no difference in reaching treatment goal between the three education groups. These findings suggest patients with higher education level achieve an earlier dyslipidemia prevention intervention with an equally satisfying result compared to lower education patients. Little is known about the role of social inequality as a possible barrier for managing hypercholesterolemia in general practice. Increasing education level was associated to less frequent measurement and less frequent statin treatment. Patients with higher education level were younger, and less comorbidity at first statin prescription. Education level had no effect on frequency of statin treatment-initiated patients reaching the treatment goal was found. [ABSTRACT FROM AUTHOR]

To effectively utilize the by-products of skipjack tuna (Katsuwonus Pelamis) for the preparation of peptides with lipid-lowering activity, alkaline proteinase was selected from six commercial proteases to hydrolyze dark muscle. An L16 (54) orthogonal design was employed to optimize the hydrolysis conditions, resulting in the production of a high-peptide-content hydrolyzate named KPHs-AL. This hydrolyzate exhibited the ability to significantly reduce TG content. KPHs-AL also showed higher persuasive pancreatic lipase (PL) and cholesterol esterase (CEase) inhibitory potential than various molecular weight (Mw) fractions and other enzymatic hydrolyzates, with IC50 values of 5.14 and 8.51 mg/mL, respectively. Furthermore, KPHs-AL exerted a combined effect of regulating lipid accumulation in FAA-induced steatosis HepG2 cells, leading to decreased total cholesterol (TC) and total triglyceride (TG). Based on the high binding likelihood and interaction with specific binding sites predicted by Pepsite2, 38 peptide sequences were identified as potential PL and CEase inhibitors. Hence, KPHs-AL holds promise as a beneficial component of functional food and exhibits the potential for anti-obesity effects through the alleviation of lipid accumulation [ABSTRACT FROM AUTHOR]

In this study, five different types of fish burgers were produced using 80% ground fish meat, 10% lipid, 6% spices mixture and 4% water. Burgers (5 mm thickness and 90 g weight) were produced using 100% fish oil (control), 75% fish oil and 25% mango kernel oil (MKO) (T1), 50% fish oil and 50% MKO (T2), 25% fish oil and 75% MKO (T3), 0% fish oil and 100% MKO (T4). Burgers were packaged in polyethylene bags and stored at −16 to −18°C for 90 days. The mangiferin, quercetin, catechin, chlorogenic and caffeic acid in MKO were 1381, 87, 512, and 973 mg/100 g. Total antioxidant capacity of control, T1, T2, T3, and T4 were 18.97, 31.47, 47.69, 65.37, and 78.82%. GC-MS analysis showed that ALA, EPA, and DHA) in T2 were 0.85, 3.62, and 4.19%. In controlled storage, loss of ALA, EPA, and DHA was 55, 14, and 11%. At T2 concentration, antioxidant compounds of MKO significantly altered the lipid oxidation in burgers. After storage in T2, loss of ALA, EPA, and DHA was 3.6, 1.98, and 1.71%. POV of 90 days stored control, T1, T2, T3, and T4 was 3.42, 1.55, 0.63, 0.41, and 0.31 (MeqO2/kg). Induction period of fish oil, MKO, in all levels was 2.45, 64.28, 7.33, 13.42, 18.39, and 62.84 hrs. Color flavor and texture score of 90 days stored T2 was 91, 90, and 86% of total score. MKO and fish oil can be used at 50:50 concentrations to formulate fish burgers of acceptable sensory properties. [ABSTRACT FROM AUTHOR]

SQSTM1/p62 (sequestosome 1) is a well-established indicator of macroautophagic/autophagic flux. It was initially characterized as the ubiquitin-binding autophagic receptor in aggrephagy, the selective autophagy of ubiquitinated protein aggregates. Recently, several studies correlated its levels with the abundance of intracellular lipid droplets (LDs). In the absence of a bona fide receptor for the selective autophagy of LDs (lipophagy), a few studies demonstrated the role of SQSTM1 in lipophagy. Our analysis of these studies shows that SQSTM1 colocalizes with LDs, bridges them with phagophores, is co-degraded with them in the lysosomes, and affects LD abundance in a variety of cells and under diverse experimental conditions. Although only one study reported all these functions together, the overwhelming and complementary evidence from other studies suggests that the role of SQSTM1 in lipophagy via tagging, movement, aggregation/clustering and sequestration of LDs is rather a common phenomenon in mammalian cells. As ubiquitination of the LD-associated proteins under stress conditions is increasingly recognized as another common phenomenon, some other ubiquitin-binding autophagic receptors, such as NBR1 and OPTN, might soon join SQSTM1 on a list of the non-exclusive lipophagy receptors. Abbreviations: LD: lipid droplet; LIR: LC3-interacting region; PAT: Perilipin, ADRP and TIP47 domain; SAR: selective autophagy receptor. [ABSTRACT FROM AUTHOR]

The objective of this experiment was to select D. hansenii isolates that are stable in dry fermented sausage (DFS) production and can positively affect the quality. D. hansenii isolates were examined for production of biogenic amines, β-glucuronidase, β-glucosidase, proteolytic, and lipolytic enzymatic activities. The acid and salt tolerance of D. hansenii isolates were also examined. DFS inoculated with selected D. hansenii isolates were analyzed for microorganisms, weight loss, Aw, and pH. DFS was also subjected to analyses of color, texture profile, reducing sugar, volatile basic nitrogen (VBN), lipid oxidation, and free fatty acid. Twenty-two D. hansenii isolates were isolated. None of these D. hansenii isolates produced biogenic amines, and all strains were negative for β-glucuronidase and β-glucosidase activities. After examining these strains for proteolysis, lipolysis, and salt and acid tolerance, D. hansenii isolates SMFM2021-C14, SMFM2021-S8, and SMFM2021-SL3 were selected to be used in DFS. During the processing of DFS, the groups treated with D. hansenii isolate SMFM2021-S8 or SMFM2021-SL3 showed lower (p <.05) hardness values of DFS. The sample treated with D. hansenii SMFM2021-S8 showed lower (p <.05) VBN and lipid oxidation contents than the others. The ratio of ω-6/ω-3 was lower (p <.05) in D. hansenii SMFM2021-SL3 treated group than in the other treatments. These results indicate that D. hansenii isolates SMFM2021-S8 and SMFM2021-SL3 might be useful in producing DFS to improve its quality. [ABSTRACT FROM AUTHOR]

This study investigated the effect of NaNO2 on inhibiting myoglobin-mediated lipid oxidation in muscle using a washed bovine mince model. We measured various parameters, including TBARS and PV to determine lipid oxidation, non-heme iron release, protoporphyrin destruction, and nitrosylmyoglobin production. The results of the study showed that the addition of NaNO2 during myoglobin-mediated lipid oxidation significantly reduced the fading and lipid oxidation of washed muscle (p < 0.05). Additionally, the addition of NaNO2 reduced the release of non-heme iron and the degradation of protoporphyrin in myoglobin. Nitrosylmyoglobin was formed in the washed mince supplemented with NaNO2 and myoglobin. These findings suggest that NaNO2 can effectively inhibit the lipid oxidation process induced by myoglobin, which could be a crucial aspect of nitrite inhibition of lipid oxidation in cured meat products. Overall, the study provides evidence for the potential use of NaNO2 as a food preservative to prevent lipid oxidation in meat products. [ABSTRACT FROM AUTHOR]

Probiotics possess many health-endorsing properties; however, their viability and stability under detrimental condition is uncertain. Encapsulation technology provides protection under various stressed conditions. Furthermore, combination of different wall materials ensures the target delivery of core materials. In the current study, probiotic was encapsulated using solid lipid micro particles (SLMP) that were prepared by high shear homogenization. Whey protein and gum Arabic were used as wall material to encapsulate the probiotics. Obtained micro beads were subjected for size, zeta potential, and encapsulation efficiency measurement. Scanning electron microscopy was used for morphological characterization of the microbeads. Molecular characterization of obtained micro beads was done by Fourier-transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). Furthermore, the viability and stability were assessed under simulated gastrointestinal conditions. Free and encapsulated probiotics were incorporated in chocolate to evaluate the stability of probiotics. The results in this study indicated that encapsulated probiotics showed significant (P <.05) viability under simulated gastrointestinal and technological conditions compared to free probiotics. A log reduction of 3.54 CFU/mL and 2.52 CFU/mL was detected for SLMW and SLMG after 120 min under simulated gastric condition while 2.42 CFU/mL log reduction and 4.13 log CFU/mL log reduction was detected under intestinal conditions. Likewise, chocolate containing encapsulated probiotics showed better viability at 4°C after 30 days of storage duration and showed significant (p <.05) results. A log reduction of 1.08 log CFU/g was observed in chocolate with Gum Arabic in SLMP as and encapsulating material. In conclusion, solid lipid particles have a strong potential to extend the viability of probiotics under detrimental circumstances. [ABSTRACT FROM AUTHOR]

Evidence suggests that intracellular angiotensin II type 1 receptor (AT1) contributes to peritoneal fibrosis (PF) under high glucose (HG)-based dialysates. It is generally believed that AT2 antagonisticly affects AT1 function. The aim of this study was to explore whether AT2 activation is beneficial for attenuating human peritoneal mesothelial cell (HPMC) injury due to HG. We treated a HPMC line with HG to induce extracellular matrix (ECM) formation. AT2 was increased and blocked using CGP42112A and AT2 siRNA. Lipid deposition was detected, signaling molecules associated with lectin-like oxidized lipoprotein receptor-1 (LOX-1) and ECM proteins were evaluated by real-time PCR and western blot. The results showed that HG led to AT2 inhibition in HPMCs, inhibition of AT2 further aggravated the expression of ECM proteins, including α-smooth muscle actin, fibroblast specific protein-1 and collagen I, while AT2 decreased the expression of ECM proteins, even during HG stimulation. Interestingly, there was a parallel change in lipid accumulation and ECM formation when AT2 was increased or depressed. Moreover, AT2-mediated decreased ECM production was associated with reduced lipid accumulation in HPMCs and depended on the downregulation of LOX-1. Further analysis showed that HG increased oxidized low-density lipoprotein (ox-LDL) deposition in HPMCs concomitant with an enhanced expression of ECM components, whereas blocking LOX-1 reversed ox-LDL deposition even in the presence of HG. This effect was also accompanied by the remission of ECM accumulation. Our results suggested that AT2 prevented ECM formation in HG-stimulated HPMCs by ameliorating lipid via LOX‐1 suppression. [ABSTRACT FROM AUTHOR]

Pigment epithelium-derived factor (PEDF) is a serin protease inhibitor and a potent inhibitor of angiogenesis. Its serum level has significant associations with metabolic parameters. However, little is known about the association between PEDF levels and lipid parameters in renal transplanted (TX) patients. Therefore, our aim was to investigate the relationship between PEDF level and lipid parameters in TX patients. Seventy TX patients (47 males, 23 females, mean age 51.7 ± 12.4 years) and 34 healthy controls were enrolled. We examined the serum creatinine, C-reactive protein, fasting glucose and lipid parameters right before, then 1 and 6 months after TX. High-density lipoprotein (HDL)-associated paraoxonase-1 (PON1) activities were measured spectrophotometrically. Lipoprotein subfractions were determined by Lipoprint. PEDF and oxidized low-density liporotein (oxLDL) levels were measured by ELISA. Before transplantation, patients had had a significantly higher PEDF level compared to control subjects (p < 0.001). One month after transplantation, their PEDF level decreased significantly reaching the healthy controls' level, and this lower level was maintained during the 6 months follow-up period as well. The initial oxLDL level was significantly higher, while PON1 activities were significantly lower in the patient group compared to the control group. We found a significant positive correlation between PEDF and total cholesterol, low-density lipoprotein (LDL)-cholesterol, triglyceride, oxLDL and small HDL subfraction; while negative correlations were found between PEDF and mean LDL size and large HDL subfraction during the entire follow-up period. PEDF may play an important role in the increased oxidative stress and enhanced atherogenesis in renal transplant patients. [ABSTRACT FROM AUTHOR]

This study was aimed to investigate the effects of trans-anethole (TA) on intestinal antioxidant status, immune function and liver lipid metabolism in broilers. A total of 256 1-day-old Arbour Acres broilers were allocated to 4 treatment groups with 8 birds per replicate. TA was added to diets at a concentration of 0 (control), 400, 600, and 800 mg/kg for 42 days. Dietary supplementation of TA increased the average daily feed intake (ADFI) of birds throughout the entire period. TA supplemented at 400 mg/kg of diet contributed to the lowest jejunal and ileal malondialdehyde (MDA) concentration on d 42, and the highest ileal total superoxide dismutase (T-SOD) activity on d 21 and d 42. TA supplementation at the concentration of 400 and 600 mg/kg of diet increased mRNA expression of ileal interleukin (IL)-4 on d 21, and intestinal secretory immunoglobulin A (sIgA) concentration on d 42. Supplementation of TA at the concentration up to 800 mg/kg of diet had adverse effects on intestinal antioxidant status, immune function and liver lipid metabolism compared with control group. Differently, TA supplemented at 400 mg/kg led to lower mRNA expression of liver ACC1, FASN, sterol regulatory element-binding protein 1c (SREBP-1), and higher CPT1 on d 42. In conclusion, TA inclusion improved intestinal antioxidant status and immune function, and enhanced liver lipid metabolism of broilers. Supplementation of 400 mg/kg of TA increased intestinal antioxidant status and immune function, and promoted liver lipid metabolism of broilers compared with non-supplemented group. [ABSTRACT FROM AUTHOR]

For the first time, the pre-hibernation sizes of "storage" organs (liver and fat bodies), the type, concentration and total content of reserve substances (glycogen or lipids) in these organs and muscle tissue, and their change during freezing in freeze tolerant specimens of the moor frog (Rana arvalis) in the Siberian population were studied. In autumn, the relative weight of the liver (hepatosomatic index) in the studied individuals reaches 10%, which is 2–4 times higher than in most species of Eurasian ranid frogs; this determines 2–4 times greater hepatic glycogen stores. The concentration of glycogen in the muscles is about 4.4 times lower than in the liver, but the total storage of glycogen in the muscles is 43–57% of the storage in the liver. The high degree of glycogen degradation upon freezing in both tissues may indicate that it is promising to search for either high levels of glucose or other cryoprotectants than in the ranid frogs studied so far. The content of lipids in the tissues in autumn is small and not completely consumed before freezing. Probably, lipids play an insignificant role in pre-winter metabolism, and are necessary for maintaining activity after overwintering. Thus, the highest freeze tolerance of the moor frog among the Eurasian ranid frogs (−14°C to −16°C in different Siberian populations) may be due to the high relative weight of the liver, which provides a large supply of glycogen before hibernation, the participation of muscle tissue in the deposition of almost a third part of all glycogen the body, significant consumption of glycogen during freezing for cryoprotectants. The patterns of storage and consumption of pre-hibernation energy resources in frogs of the genus Rana differ greatly not only between terrestrial and aquatic hibernators but also between freeze tolerant species. [ABSTRACT FROM AUTHOR]

Our study investigated whether lipid emulsion therapy could act as an antidote for intravenous amiodarone toxicity in a rat model. 20 rats were randomised to receive lipid emulsion (ILE) or saline. Rats were infused with amiodarone at 1 mg/kg/min for 20 min. ILE rats then received 6 mL/kg of IV 20% ILE, with controls receiving saline. Amiodarone infusion then recommenced at 0.25 mg/kg/minute for 15 min. Heart rate and mean arterial pressure (MAP) were recorded at the commencement and end of the first amiodarone infusion, and every 5 min during the second amiodarone infusion until experiment termination. Blood was sampled for amiodarone concentration at the conclusion of each infusion. At experiment termination MAP was greater for the ILE group (85 vs 60 mmHg, p = 0.01), with no difference in heart rate between groups (224 vs 232 bpm, p = 0.19). Amiodarone concentration decreased after saline treatment and was stable after ILE (change −6.4 micromol/L saline, 0.11 micromol/L lipid p < 0.001) ILE therapy mitigated intravenous amiodarone-induced hypotension in this rat model. While amiodarone was retained in lipid treated blood the quantum of this increase did not support the "lipid sink" hypothesis. Further research is required to evaluate the clinical relevance of these findings. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the effect of multilamellar vesicles (MLVs) of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) in co-culture with in vitro-produced bovine embryos (IVPEs). The stability of five concentrations of MLVs (1.0, 1.25, 1.5, 1.75, and 2.0 mM) produced using ultrapure water or embryonic culture medium with 24 or 48 h of incubation at 38.5 °C with 5% CO2 was assessed. In addition, the toxicity of MLVs and their modulation of the lipid profile of the plasma membrane of IVPEs were evaluated after 48 h of co-culture. Both media allowed the production of MLVs. Incubation (24 and 48 h) did not impair the MLV structure but affected the average diameter. The rate of blastocyst production was not reduced, demonstrating the nontoxicity of the MLVs even at 2.0 mmol/L. The lipid profile of the embryos was different depending on the MLV concentration. In comparison with control embryos, embryos cultured with MLVs at 2.0 mmol/L had a higher relative abundance of six lipid ions (m/z 720.6, 754.9, 759.0, 779.1, 781.2, and 797.3). This study sheds light on a new culture system in which the MLV concentration could change the lipid profile of the embryonic cell membrane in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Atorvastatin (ATV) has attracted considerable attention as a potential therapeutic agent for cancer because it inhibits cancer cell proliferation by suppressing the mevalonate pathway. However, because of its low oral absorption, high doses of ATV are required for chemotherapeutic applications. In this study, we constructed ATV-loaded nanoemulsions (ATV-NEs) containing multivalent intestinal transporter-targeting lipids to improve the oral bioavailability of ATV. ATV-NEs were prepared via oil-in-water emulsification for transporter-targeted delivery, and contained the following anchors: an ionic complex of deoxycholic acid (DOCA) with the cationic lipid 1,2-dioleyl-3-trimethylammonium propane (DOTAP) (DOCA-DOTAP), a biotin-conjugated lipid (Biotinyl PE), and d-alpha-tocopherol polyethylene glycol succinate (TPGS) to allow bile acid- and multivitamin transporter-mediated permeation of ATV without P-glycoprotein (P-gp)-mediated efflux. The optimized formulation (ATV-NE#6) had 1,091% higher oral bioavailability than free ATV. Finally, treatment of 4T1 cell-bearing mice with oral ATV-NE#6 (equivalent to 40 mg/kg ATV) significantly suppressed tumor growth; the maximum tumor growth reduction was 2.44-fold that of the control group. The results thus suggest that ATV-NEs allow for effective oral chemotherapy by enhancing the oral bioavailability of ATV. [ABSTRACT FROM AUTHOR]

Plant-derived 5 a-reductase inhibitors, such as β-sitosterol and phytosterol glycosides, have been used to treat androgenic alopecia, but their oral absolute bioavailability is poor. This study aimed to develop a transdermal drug delivery system of β-sitosterol (BS) using a nanostructured lipid carrier (NLC) incorporated into polymeric microneedles (MN). Using a high-speed homogenization method, NLC was formulated variables were optimized by Box-Behnken statistical design. The optimized formulation of BS-loaded NLCs was incorporated into the chitosan-based MNs to prepare NLC-loaded polymeric MNs (NLC-MNs) and evaluated using testosterone induced alopecia rats. The cumulative amount of β-sitosterol associated with NLC-MN which penetrated the rat skin in-vitro was 3612.27 ± 120.81 μg/cm², while from the NLC preparation was 2402.35 ± 162.5 μg/cm². The steady state flux (Jss) of NLC-MN was significantly higher than that of the optimized NLC formulation (P < 0.05). Anagen/telogen ratio was significantly affected by NLC and NLC-MN, which was 2.22 ± 0.34, 1.24 ± 0.18 respectively compared to 0.26 ± 0.08 for animal group treated with testosterone. The reversal of androgen-induced hair loss in animals treated with β-sitosterol was a sign of hair follicle dominance in the anagenic growth phase. However, NLC-MN delivery system has shown significant enhancement of hair growth in rats. From these experimental data, it can be concluded that NLC incorporated MN transdermal system have potential in effective treatment of androgenic alopecia. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) is one of the most common ischemic heart diseases. However, lack of sufficient drug concentration (in the ischemic heart) is the major factor of treatment failure. It is urgent for researchers to engineer novel drug delivery systems to enhance the targeted delivery of cardioprotective agents. The aim of the present study was to investigate the anti-AMI ability of calycosin (CAL) and tanshinone (TAN) co-loaded; mitochondrion-targeted tetrapeptide (MTP) and cyclic arginyl-glycyl-aspartic acid (RGD) peptide co-modified nano-system.: We prepared CAL and TAN combined lipid-polymer hybrid nano-system, and RGD was modified to the system to achieve RGD-CAL/TAN NS. MTP-131 was conjugated with PEG and modified onto the nanoparticles to achieve dual ligands co-modified MTP/RGD-CAL/TAN NS. The physicochemical properties of nano-systems were characterized. The AMI therapy ability of the systems was investigated in AMI rats' model. The size of MTP/RGD-CAL/TAN NS was 170.2 ± 5.6 nm, with a surface charge of -18.9 ± 1.9 mV. The area under the curve (AUC) and blood circulation half-life (T1/2) of MTP/RGD-CAL/TAN NS was 178.86 ± 6.62 µg·min/mL and 0.47 h, respectively. MTP/RGD-CAL/TAN NS exhibited the most significant infarct size reduction effect of 22.9%. MTP/RGD-CAL/TAN NS exhibited the highest heart accumulation and best infarct size reduction effect, which could be used as a promising system for efficient treatment of cardiovascular diseases. [ABSTRACT FROM AUTHOR]

The main aim of this study was to improve the therapeutic potential of a paclitaxel (PTX) and curcumin (CU) combination regimen using solid lipid nanoparticles (SLNs). PTX and CU were successfully coencapsulated at a predetermined ratio in SLNs (PC-SLNs) with high encapsulation efficiency (CU: 97.6%, PTX: 95.8%), appropriate particle size (121.8 ± 1.69 nm), small PDI (0.267 ± 0.023), and negative zeta potential (-30.4 ± 1.25 mV). Compared with PTX or the combination of CU and PTX (CUþPTX), PC-SLNs can greatly reduce the dose of PTX while still achieving the same therapeutic effect on four cancer cell lines, among which the inhibitory effect on A549 lung cancer cells was the strongest. PCSLNs improved the area under the curve (CU: 1.40-fold; PTX: 2.88-fold), prolonged the residence time (CU: 6.94-fold; PTX: 2.51-fold), and increased the half-life (CU: 5.62-fold; PTX: 6.46-fold), achieving long circulation. PC-SLNs were used to treat lung cancer in a nude mouse xenograft tumor model and the tumor suppression rate reached 78.42%, while those of PTX and (CUþPTX) were 40.53% and 51.56%, respectively. As PC-SLNs can prevent P-glycoprotein efflux, reverse MDR and downregulate the NF-jB pathway. PC-SLNs are a potential antineoplastic agent that is more effective and less toxic in treating lung cancer. [ABSTRACT FROM AUTHOR]

Antipsychotics are accompanied by extrapyramidal side effects that deter treatment adherence and patient compliance. Paliperidone (PPD), an atypical (second-generation) antipsychotic recommended for managing schizophrenia presents biopharmaceutical challenges and pharmacological constraints which dissuade it from crossing the brain barrier. The present research aimed to assess paliperidoneloaded lipid nanoconstruct (PPD-LNC) for an improved antipsychotic activity for managing schizophrenia. High % cell viability in Neuro-2a cells (70-98%) exhibited the safety of PPD-LNC. The pharmacokinetic data showed a 3.46-fold improvement in the relative bioavailability in the brain for PPD-LNC compared to a drug suspension. The pharmacodynamic evaluation demonstrated a significant (p<.05) reduction in cataleptic behavior, attenuated escape latency, and prolonged stay in the open arm with PPD-LNC, thus showing its effectiveness in reducing extrapyramidal symptoms. The histopathological images further validated the safety of the formulation. Reduction in NF-κB levels as identified by immunohistochemical analysis exhibited the anti-inflammatory effect of PPD-LNC. The formulation demonstrated significant (p<.01) improvement in the activity of oxidative stress parameters and attenuation of neuroinflammatory markers. Based on the study findings, it was observed that formulating LNC of PPD would surmount the pharmacological constraints, improve the in vivo performance, and diminish the associated side effects. [ABSTRACT FROM AUTHOR]

Entacapone, a reversible catechol-o-methyl transferase inhibitor, is used to enhance the action of dopamine agonists by reducing their metabolism and the 'Wearing-off' effects associated with longterm use in the treatment of Parkinson's disease. It is used as an adjunct to levodopa/Carbidopa therapy. Due to limited dissolution and first-pass clearance, it suffers low and variable bioavailability issues. To overcome this problem, the present study aims to explore the potential of nanostructured lipid carriers (NLCs) for the delivery of Entacapone. The Quality by Design (QbD) approach was used for the systematic development of NLCs. The 23 full factorial designs were investigated using Design-ExpertVR 11 software. The three independent variables namely content of total lipid (X1), surfactant (X2), and sonication time (X3) were optimized against two responses namely particle size and entrapment efficiency. The optimized NLCs were characterized for their size, surface morphology, entrapment efficiency, drug release, thermal and crystallographic studies. In-vivo pharmacokinetic studies in Entacapone-loaded NLCs showed an increase in t1/2, AUC0-1, MRT compared to free drug. The reduction in elimination (Kel) depicts the prolonged action of Entacapone by loading in NLCs. The results displayed Entacapone-loaded NLCs have promising potential for oral delivery and enhanced therapeutic effect which otherwise was a major issue. [ABSTRACT FROM AUTHOR]

Sorafenib (SRB), a multikinase inhibitor, is effective in reducing experimental corneal neovascularization (CNV) after oral administration; however, its therapeutic use in ocular surface disorders is restricted due to poor solubility and limited bioavailability. This study aimed to develop and optimize SRBloaded nanostructured lipid carriers (SRB-NLCs) for topical ocular delivery by a central composite design response surface methodology (CCD-RSM). It was spherical and uniform in morphology with an average particle size of 111.87 ± 0.93nm and a narrow size distribution. The in vitro drug release from the released SRB-NLC formulation was well fitted to Korsmeyer Peppas release kinetics. The cell counting kit-8 (CCK-8) cell viability assay demonstrated that SRB-NLC was not obviously cytotoxic to human corneal epithelial cells (HCECs). An in vivo ocular irritation test showed that SRB-NLC was well tolerated by rabbit eyes. Ocular pharmacokinetics revealed 6.79-fold and 1.24-fold increase in the area under concentration-time curves (AUC0-12h) over 12 h in rabbit cornea and conjunctiva, respectively, treated with one dose of SRB-NLC compared with those treated with SRB suspension. Moreover, SRB-NLC (0.05% SRB) and dexamethasone (0.025%) similarly suppressed corneal neovascularization in mice. In conclusion, the optimized SRB-NLC formulation demonstrated excellent physicochemical properties and good tolerance, sustained release, and enhanced ocular bioavailability. It is safe and potentially effective for the treatment of corneal neovascularization. [ABSTRACT FROM AUTHOR]

Nanoparticles for colon-drug delivery were designed and evaluated to solve many discrepancy issues such as high adverse effects of released drugs, insufficient drug amount at diseased areas, and unintentionally premature drug release to noninflamed GIT regions. Herein, the goal of this work was to convert trimebutine maleate (TMB) into nanostructured lipid carriers (NLC) in order to improve its protective effects in ulcerative colitis. NLC of TMB was prepared by the hot homogenization followed by ultra-sonication method. A full 4²-factorial design was used to estimate the produced TMB-NLC. The study design included the exploration of the impact of two independent variables namely lipid mix amount and ratio (glyceryl mono stearate and capryol 90), surfactant concentration (0.5, 1, 1.5, and 2%), on the particle size, polydispersity index, and the entrapment efficiency (EE%). The protective activity of F9 was examined through macroscopical scores, histopathological changes, immunohistochemical localization of tumor necrosis factor-a (TNF-a) and examination of oxidative stress such as reduced glutathione (GSH), superoxide dismutase (SOD), and malondialdehyde (MDA) against acetic acid-induced colitis in rats. Consistent with our expectations, the orally administered optimized formula (F9) alleviated the severity of colitis in acetic acid-induced rat model of colitis likely owing to the controlled release compared to free TMB. We aimed to develop TMB-loaded NLC for the treatment of acute colitis with the goal of providing a superior drug safety profile over long-term remission and maintenance therapy. [ABSTRACT FROM AUTHOR]

Purpose: Colorectal cancer (CRC) is the third most frequently diagnosed cancer and this study aimed to develop a conatumumab decorated, irinotecan prodrug and quercetin co-loaded delivery system for combined and targeted colorectal cancer treatment. Methods: A conatumumab (C) decorated, irinotecan prodrug (I-p) and quercetin (Q) co-encapsulated NLC (C I-p/Q NLC) was developed. In vitro and in vivo antitumor efficiency of NLC was evaluated on CRC cells and mice xenograft. Results: The results showed that the HT-29 cells uptake of C I-p/Q NLC was over 70%. Reactive oxygen species (ROS) sensitive irinotecan prodrug formulation showed improved drug release ability in hypoxic conditions. C I-p/Q NLC showed significantly higher cytotoxicity than non-decorated NLC, single drug-loaded NLC and free drugs. In vivo studies in a CRC-bearing model corroborated the capability of nanoparticles for the inhibition of cancer, leading to a reduction of tumor growth without systemic toxicity. Conclusion: The conatumumab decorated, ROS sensitive prodrug contained combination nano-system is a promising platform for CRC therapy. [ABSTRACT FROM AUTHOR]

Nanocapsules can be equated to other nanovesicular systems in which a drug is entrapped in a void containing liquid core surrounded by a coat. The objective of the present study was to investigate the potential of polymeric and lipid nanocapsules (LNCs) as innovative carrier systems for miconazole nitrate (MN) topical delivery. Polymeric nanocapsules and LNCs were prepared using emulsification/nanoprecipitation technique where the effect of poly(e-caprolactone (PCL) and lipid matrix concentrations with respect to MN were assessed. The resulted nanocapsules were examined for their average particle size, zeta potential, %EE, and in vitro drug release. Optimum formulation in both polymeric and lipidic nanocapsules was further subjected to anti-fungal activity and ex vivo permeation tests. Based on the previous results, nanoencapsulation strategy into polymeric and LNCs created formulations of MN with slow biphasic release, high %EE, and improved stability, representing a good approach for the delivery of MN. PNCs were best fitted to Higuchi's diffusion while LNCs followed Baker and Lonsdale model in release kinetics. The encapsulated MN either in PNCs or LNCs showed higher cell viability in WISH amniotic cells in comparison with free MN. PNCs showed less ex vivo permeation. PNCs were accompanied by high stability and more amount drug deposition (32.2 ± 3.52 μg/cm²) than LNCs (12.7 ± 1.52 μg/cm²). The antifungal activity of the PNCs was high 19.07mm compared to 11.4mm for LNCs. In conclusion, PNCs may have an advantage over LNCs by offering dual action for both superficial and deep fungal infections. [ABSTRACT FROM AUTHOR]

Candida albicans is the fungus responsible for oral candidiasis, a prevalent disease. The development of antifungal-based delivery systems has always been a major challenge for researchers. This study was designed to develop a nanostructured lipid carrier (NLC) of sesame oil (SO) loaded with miconazole (MZ) that could overcome the solubility problems of MZ and enhance its antifungal activity against oral candidiasis. In the formulation of this study, SO was used as a component of a liquid lipid that showed an improved antifungal effect of MZ. An optimized MZ-loaded NLC of SO (MZ-SO NLC) was used, based on a central composite design-based experimental design; the particle size, dissolution efficiency, and inhibition zone against oral candidiasis were chosen as dependent variables. A software analysis provided an optimized MZ-SO NLC with a particle size of 92 nm, dissolution efficiency of 88%, and inhibition zone of 29 mm. Concurrently, the ex vivo permeation rate of the sheep buccal mucosa was shown to be significantly (p<.05) higher for MZ-SO NLC (1472 mg/cm2) as compared with a marketed MZ formulation (1215 mg/cm2) and an aqueous MZ suspension (470 mg/cm2). Additionally, an in vivo efficacy study in terms of the ulcer index against C. albicans found a superior result for the optimized MZ-SO NLC (0.5 ± 0.50) in a treated group of animals. Hence, it can be concluded that MZ, through an optimized NLC of SO, can treat candidiasis effectively by inhibiting the growth of C. albicans. [ABSTRACT FROM AUTHOR]

Combination therapy combining two drugs in one modified drug delivery system is used to achieve synergistic analgesic effect, and bring effective control of pain management, especially postoperative pain management. In the present study, a combination of drug delivery technologies was utilized. Transcriptional transactivator (TAT) peptide modified, transdermal nanocarriers were designed to codeliver ropivacaine (RVC) and meloxicam (MLX) and anticipated to achieve longer analgesic effect and lower side effect. TAT modified nanostructured lipid carriers (TAT-NLCs) were used to co-deliver RVC and MLX. RVC and MLX co-loaded TAT-NLCs (TAT-NLCs-RVC/MLX) were evaluated through in vitro skin permeation and in vivo treatment studies. NLCs-RVC/MLX showed uniform and spherical morphology, with a size of 133.4 ± 4.6nm and a zeta potential of 20.6 ± 1.8 mV. The results illustrated the anesthetic pain relief ability of the present constructed system was significantly improved by the TAT modification through the enhanced skin permeation efficiency and the co-delivery of MLX along with RVC that improved pain management by reducing inflammation at the injured area. This study provides an efficient and facile method for preparing TAT-NLCs-RVC/MLX as a promising system to achieve synergistic analgesic effect. [ABSTRACT FROM AUTHOR]

Breast cancer is one of the most common types of cancer in female patients with high morbidity and mortality. Multi-drug chemotherapy has significant advantages in the treatment of malignant tumors, especially in reducing drug toxicity, increasing drug sensitivity and reducing drug resistance. The objective of this research is to fabricate lipid nanoemulsions (LNs) for the co-delivery of PTX and docosahexaenoic acid (DHA) with folic acid (FA) decorating (PTX/DHA-FA-LNs), and investigate the antitumor activity of the PTX/DHA-FA-LNs against breast cancer both in vitro and in vivo. PTX/DHA-FA-LNs showed a steady release of PTX and DHA from the drug delivery system (DDS) without any burst effect. Furthermore, the PTX/DHA-FA-LNs exhibited a dose-dependent cytotoxicity and a higher rate of apoptosis as compared with the other groups in MCF-7 cells. The cellular uptake study revealed that this LNs were more readily uptaken by MCF-7 cells and M2 macrophages in vitro. Additionally, the targeted effect of PTX/DHA-FA-LNs was aided by FA receptor-mediated endocytosis, and its cytotoxicity was proportional to the cellular uptake efficiency. The anti-tumor efficiency results showed that PTX/DHA-FA-LNs significant inhibited tumor volume growth, prolonged survival time, and reduced toxicity when compared with the other groups. These results indicated that DHA increases the sensitivity of tumor cells and tumor-associated macrophages (ATM2) to PTX, and synergistic effects of folate modification in breast cancer treatment, thus PTX/DHA-FA-LNs may be a promising nanocarrier for breast cancer treatment. [ABSTRACT FROM AUTHOR]

The domestic yak was regarded as a valuable model to explore the molecular mechanism of high-altitude animal adaptation, including the extreme tolerance of starvation and cold stress, which is closely associated with specifically seasonal deposition and metabolism of subcutaneous adipose tissue. However, the key regulators for these processes remain largely unknown. Here, the yak adipogenesis model in vitro was established and liver kinase b1 (LKB1) was regarded as a key negative regulator involved in yak adipocytes lipid accumulation. First, the mRNA level of LKB1 in adipose tissue of yaks from the cold season is significantly higher than that of yaks from the warm season. Interestingly, overexpression of LKB1 significantly inhibited adipocytes lipid accumulation. Consistently, LKB1 overexpression dramatically suppressed mRNA levels of adipogenic transcriptional factors, including C/EBPα, C/EBPβ and PPARγ, and subsequently significantly decreased levels of lipid accumulation related genes (FABP4 and FAS) compared with those of control. In contrast, overexpression of LKB1 promoted thermogenic and lipolysis related genes in yak adipocyte, including PGC1α, PPARα, UCP1, ATGL, HSL and LPL. Therefore, these results would provide new insights to decipher the network for domestic yak adipose deposition, and LKB1 might be as a new molecular target for animal environmental-resistant breeding. [ABSTRACT FROM AUTHOR]

The lipid profile of milk from grazing goats supplemented with vegetable oils was evaluated. Twenty-seven Saanen goats consuming pasture were grouped and supplemented with 3 concentrates: without added oil (control, C) and with added sunflower (SFO) or soybean oil (SBO) until 6% ether extract (diet basis). Fat content and sensory profile of milk were not modified. Vaccenic acid increased for SBO and SFO (1.5% vs. 2.6% and 2.7% respectively; p < 0.01), and cis-9, trans-11 conjugated linoleic acid from 0.6% to 0.8% for treated groups (p < 0.01). Oil supplementation resulted effective to decrease the saturated/unsaturated ratio of grazing goat's milk. [ABSTRACT FROM AUTHOR]

The current study aimed to investigate whether the pattern of changes in lipid profile and fasting blood sugar (FBS) can predict the future risk of type 2 diabetes mellitus (T2DM) incidence in prediabetic people. In a prospective cohort study, 1228 prediabetic patients were followed from 2003 until 2019 and longitudinal data on lipid indices (CHOL: cholesterol; HDL: high-density lipoprotein; LDL: low-density lipoprotein; TG: triglyceride) and fasting blood sugar (FBS) were recorded. The latent class growth model (LCGM) was used to estimate growth trajectories and to determine distinct subgroups (latent class) with a similar trajectory for lipid profile and FBS over time. The incidence of T2DM in extracted latent classes was compared. Finally, 946 people with complete data were included in statistical analysis. Two latent classes were identified based on the change in FBS including high-risk and low-risk classes (class size: 5.2% vs. 94.8%) with T2DM incidence rates 100% and 35.9%, respectively (P < 0.001). Two distinct subgroups were identified based on changes in lipid profile. Latent classes with abnormal TG, CHOL, HDL, and LDL included 18.8%, 21.8%, 38.8%, and 24% of study participants, respectively. The incidence rates of T2DM and remaining prediabetic in abnormal TG latent class were 57.2% and 30.8%, and in abnormal HDL latent class were 41.5% and 31.7% were significantly different from normal latent classes (P < 0.001). While in the extracted latent classes based on CHOL and LDL the incidence rates were not statistically significant differences (P > 0.05). We identified two subgroups with high and low risk of future T2DM based on the changes in FBS and lipid profile by applying LCGM. The incidence of T2DM in extracted latent classes was significantly different. LCGM is a reliable approach for predicting the risk of T2DM incidence based on trajectories of risk factors. [ABSTRACT FROM AUTHOR]

To determine the clinical effects of ocular surface and Meibomian gland parameters on tear film stability among individuals with Meibomian gland dysfunction (MGD), those with aqueous deficient dry eye (ADDE), individuals with both conditions and normal controls. Patients were divided into four groups: normal controls, patients with ADDE, patients with MGD, and patients who fulfilled diagnostic criteria for ADDE and MGD (Mixed Group). Data for ocular symptom score, lid margin abnormality, ocular staining, tear break-up time, meiboscore, and lipid layer thickness (LLT) measured by a Lipiview interferometer, Schirmer test, and MGD severity score were collected. A total of 109 patients (109 eyes) were evaluated. In patients with MGD, LLT was significantly lower than the ADDE patients. However, the Schirmer test value was the highest in the MGD group. The LLT negatively correlated with meiboscore and MGD severity score in the MGD group. Significant correlation between Schirmer test value and meiboscore was definite in the MGD group. Tear fluid secretion is more increased and lipid layer thickness is more decreased in MGD patients than in ADDE patients. Decreased lipid layer thickness caused by MGD-related tear film instability may stimulate reflex tear secretion. The obstructive MGD is more prevalent than hypersecretary MGD. The tear film stability is affected by Mebomian gland dysfunction (MGD). The measurement of the tear film parameters including lipid layer thickness suggests that the obstructive MGD is more prevalent than hypersecretary MGD and the aqueous layer compensates the decreased lipid layer caused by MGD. [ABSTRACT FROM AUTHOR]

POME is an excellent cultivation medium for the production of microalgae because it includes high macro and micronutrients. Nevertheless, microalga cultivation is laborious to maintain under outdoor condition. The aim of this reseasch was to evaluate the potency of co-cultivation strategy to improve growth and lipid production of mixed algae when growing on POME under dynamic outdoor condition. Cultivation was done in outdoor condition by comparing synthetic medium and POME medium, and optimizing the enviromental and nutritional conditions by using Box-behnken response surface methodology (RSM). Results showed that high growth rate (0.35/d) and lipid (40%) were achieved when 75% POME fraction, 30 PSU salinity, and 450 mg/L urea were used. The increasing POME fraction and urea addition enhanced SFA formation to MUFA and PUFA in the fatty acid profiles. We conclude that co-cultivation strategy on POME could promote growth rate and lipid production of mixed algae under outdoor condition. [ABSTRACT FROM AUTHOR]

The endolysosomal system not only is an integral part of the cellular catabolic machinery that processes and recycles nutrients for synthesis of biomaterials, but also acts as signaling hub to sense and coordinate the energy state of cells with growth and differentiation. Lysosomal dysfunction adversely influences vesicular transport-dependent macromolecular degradation and thus causes serious problems for human health. In mammalian cells, loss of the lysosome associated membrane proteins LAMP1 and LAMP2 strongly affects autophagy and cholesterol trafficking. Here we show that the previously uncharacterized Drosophila Lamp1 is a bona fide ortholog of vertebrate LAMP1 and LAMP2. Surprisingly and in contrast to lamp1 lamp2 double-mutant mice, Drosophila Lamp1 is not required for viability or autophagy, suggesting that fly and vertebrate LAMP proteins acquired distinct functions, or that autophagy defects in lamp1 lamp2 mutants may have indirect causes. However, Lamp1 deficiency results in an increase in the number of acidic organelles in flies. Furthermore, we find that Lamp1 mutant larvae have defects in lipid metabolism as they show elevated levels of sterols and diacylglycerols (DAGs). Because DAGs are the main lipid species used for transport through the hemolymph (blood) in insects, our results indicate broader functions of Lamp1 in lipid transport. Our findings make Drosophila an ideal model to study the role of LAMP proteins in lipid assimilation without the confounding effects of their storage and without interfering with autophagic processes. Abbreviations: aa: amino acid; AL: autolysosome; AP: autophagosome; APGL: autophagolysosome; AV: autophagic vacuole (i.e. AP and APGL/AL); AVi: early/initial autophagic vacuoles; AVd: late/degradative autophagic vacuoles; Atg: autophagy-related; CMA: chaperone-mediated autophagy; Cnx99A: Calnexin 99A; DAG: diacylglycerol; eMI: endosomal microautophagy; ESCRT: endosomal sorting complexes required for transport; FB: fat body; HDL: high-density lipoprotein; Hrs: Hepatocyte growth factor regulated tyrosine kinase substrate; LAMP: lysosomal associated membrane protein; LD: lipid droplet; LDL: low-density lipoprotein; Lpp: lipophorin; LTP: Lipid transfer particle; LTR: LysoTracker Red; MA: macroautophagy; MCC: Manders colocalization coefficient; MEF: mouse embryonic fibroblast MTORC: mechanistic target of rapamycin kinase complex; PV: parasitophorous vacuole; SNARE: soluble N-ethylmaleimide sensitive factor attachment protein receptor; Snap: Synaptosomal-associated protein; st: starved; TAG: triacylglycerol; TEM: transmission electron microscopy; TFEB/Mitf: transcription factor EB; TM: transmembrane domain; tub: tubulin; UTR: untranslated region. [ABSTRACT FROM AUTHOR]

Studies in children and adults have reported variations in 25-hydroxyvitamin D (25(OH)D), body mass index (BMI) and blood pressure (BP) over time. Furthermore, there has been a reported association of 25(OH)D with BMI, BP and lipid levels in some cross-sectional and longitudinal studies. This is a longitudinal study of a group of adolescents with measurements of 25(OH)D, BP, anthropometry and lipids at the ages of 11, 12 13, 15 and 18–20 years. For age-related changes, year 12 participants (n = 261) were matched with year 18–20 participants (n = 368), resulting in 200 paired participants. Longitudinal analyses using the Generalized Estimating Equations (GEE) comprised the following groups of participants, Year 11 (n = 288), Year 12 (n = 253), Year 13 (n = 292), Year 15 (n = 238) and Year 18–20 (n = 368). The relationship of 25(OH)D with BMI, BP and lipid levels over a period of 10 years was assessed. There were significant increases in mean BMI and BP, and decreases in 25(OH)D levels with age (all p-values < 0.0001). In females, systolic BP was significantly higher in older participants (18–20) years than younger participants (12 years), but 25(OH)D was significantly higher in younger than older participants. In males, there was significant increase in BP in participants between age 12 years and 18–20 years. 25(OH)D, total cholesterol (TC) and low-density lipoprotein (LDL-C) were significantly lower in 18–20-year-old participants compared with 12-year-old participants. Longitudinally, 25(OH)D was inversely associated with LDL-C. There is evidence of changes in 25(OH)D, BMI and BP in adolescents over a period of 10 years. After adjusting for covariates, BMI and LDL-C were significantly negatively associated with 25(OH)D, which suggests that vitamin D status might be associated positively with favourable lipid profiles in children and adolescents. [ABSTRACT FROM AUTHOR]

In order to provide a basis for understand the potential of nisin and ε-polylysine (ε-PL) single use on replace or reduce nitrite in dry cured meat products, this study evaluated the effect of nisin and ε-PL on the microbial communities, biogenic amine (BA) formation, and lipid oxidation during storage in Chinese dry sausages not packaged. Our results revealed that the total proportion of the potentially beneficial bacteria (Lactococcus, Pediococcus, and Staphylococcus) were 22.6%-34.8% in the control, 19.5%-48.2% in the nisin treatment, and 16.2% −22.4% in the ε-PL treatment. The ε-PL had significantly lower total biogenic amine concentrations before 10 days. Putrescine (67.1–275 mg/kg) and tyramine (30.4–216 mg/kg) are the two main BAs in all treatments of dry sausages. Staphylococcus, Proteus, Enterococcus, and Klebsiella were the main bacteria genera that had a significant (P < 0.05) positive correlation to BAs accumulations. Except for day 10, nisin and ε-PL treatments could significantly reduce lipid oxidation during storage. [ABSTRACT FROM AUTHOR]