Innovative assessment of lipid-induced oxidative stress and inflammation in harvested human endothelial cells.

Studying acute changes in vascular endothelial cells in humans is challenging. We studied ten African American women and used the J-wire technique to isolate vein endothelial cells before and after a four-hour lipid and heparin infusion. Dynamic changes in lipid-induced oxidative stress and inflammatory markers were measured with fluorescence-activated cell sorting. We used the surface markers CD31 and CD144 to identify human endothelial cells. Peripheral blood mononuclear cells isolated from blood were used as a negative control. The participants received galantamine (16 mg/day) for 3 months. We previously demonstrated that galantamine treatment effectively suppresses lipid-induced oxidative stress and inflammation. In this study, we infused lipids to evaluate its potential to increase the activation of endothelial cells, as assessed by the levels of CD54+ endothelial cells and expression of Growth arrest-specific 6 compared to the baseline sample. Further, we aimed to investigate whether lipid infusion led to increased expression of the oxidative stress markers IsoLGs and nitrotyrosine in endothelial cells. This approach will expedite the in vivo identification of novel pathways linked with endothelial cell dysfunction induced by oxidative stress and inflammatory cytokines. This study describes an innovative method to harvest and study human endothelial cells and demonstrates the dynamic changes in oxidative stress and inflammatory markers release induced by lipid infusion.

Asterias Rolleston starfish gonad lipids: A novel source of Omega-3 fatty acids - assessment of major components and their antioxidant activities.

The major lipids and antioxidant activities of Asterias rolleston gonad lipids were evaluated systematically. Major lipids of A. Rolleston gonad lipids were triacylglycerols (TAGs) and phospholipids (PLs). Total lipids were composed of 15.62% of polyunsaturated fatty acids (PUFAs), and 40.81% of monounsaturated fatty acids (MUFAs). The most abundant PUFA were C20:5n-3 (EPA) (6.28%) and C22:6n-3 (DHA) (5.80%). Predominantly composed of phosphatidylcholine (PC) and phosphatidylethanolamine (PE), polar lipids were rich in PUFAs and could contain up to 34.59% EPA and DHA, and PE and PI (phosphatidylinositol) were also found to be the main carriers of EPA and ARA (arachidonic acid) in polar lipids. The MUFA and PUFA of Sn-2 in TAG are 39.72% and 30.37%, respectively. A total of 64 TAG species were identified, with Eo-P-M, Eo-Eo-M, and M-M-Eo being the main TAGs components. Moreover, A. rollestoni gonad lipids exhibited potent radical scavenging activities and reducing power in a dose-dependent manner.

Advancing vaccine development: Evaluation of a mannose-modified lipid nanoparticle-based candidate for African swine fever p30 mRNA vaccine eliciting robust immune response in mice.

The African swine fever virus (ASFV) continues to pose significant economic and pandemic risks. Consequently, discovering new, efficient vaccines is crucial. Messenger RNA (mRNA) vaccines have emerged as promising candidates, providing minimal risk of insertional mutagenesis, high safety profiles, effectiveness, rapid scalability in production, and cost-effectiveness. In this study, we have developed an ASF p30 mRNA vaccine candidate (mRNA/Man-LNP) employing mannose-modified lipid nanoparticles (LNPs). The mRNA/Man-LNP exhibited effective antigen presentation and facilitated dendritic cells (DCs) maturation. Notably, it elicited strong IgG titers and activated CD4+ and CD8+ T-cells in immunized mice, all while adhering to stringent biosafety standards. This investigation demonstrates that mRNA/Man-LNP can trigger both humoral and cellular immune responses, suggesting its potential as a potent and promising vaccine candidate for controlling African swine fever (ASF).

Turning food waste to microbial lipid towards a superb economic and environmental sustainability: An innovative integrated biological route.

With the drastic growth of the economic and population, the global energy requirement is on the rise, and massive human and material resources have been put into the development of alternative and renewable energy sources. Biodiesel has been recognized as a green and sustainable alternative energy, but the raw materials-associated source and cost makes it difficult to achieve large-scale commercial production. Microbial lipids (ML) produced by oleaginous microbes have attracted more and more topics as feedstocks for biodiesel production because of their unique advantages (fast growth cycle, small footprint and so on). However, there are still many problems and challenges ahead towards commercialization of ML-based biodiesel, especially the cost of feedstock for ML production. Food waste (FW) rich in organic matters and nutrients is an excellent and almost zero-cost feedstock for ML production. However, current biological routes of FW-based ML production have some defects, which make it impossible to achieve full industrialization at present. Therefore, this review intends to provide a critical and comprehensive analysis of current biological routes of FW-based ML production with the focus on the challenges and solutions forward. The biological routes towards future FW-based ML production must be able to concurrently achieve economic feasibility and environmental sustainability. On this condition, an innovative integrated biological route for FW-based ML production has thus been put forward, which is also elucidated on its economic and environmental sustainability. Moreover, the prospective advantages, limitations and challenges for future scale-up of FW-based ML production have also been outlined, together with the perspectives and directions forward.

Lipid Profile and Atherogenic Risk Assessment in Nigerian Breast Cancer Patients - A Cross-Sectional Study.

BACKGROUND: The lipid profile and atherogenic risk indices in Nigerian breast cancer patients are largely unknown. This study evaluated the lipid profile and atherogenic risk indices of breast cancer patients in Nigeria. METHODS: This study involved 45 primarily diagnosed breast cancer patients and 50 normal control subjects. Total cholesterol, triglyceride, and High-density lipoprotein cholesterol (HDL-C) were measured. Low-density lipoprotein cholesterol (LDL-C) was calculated according to Friedewald formula. Atherogenic index of plasma (AIP), Atherogenic coefficient (AC), TC/HDL-C (Castelli I) and LDL-C/HDL-C (Castelli II) risk indices were all calculated. The Framingham risk assessment was calculated and categorized. RESULTS: The study group had significantly higher triglycerides (TG), and atherogenic indices than the control group (p < 0.001), while HDL-Cholesterol (HDL-C) was significantly lower in the study group (p < 0.001). Total cholesterol and LDL-Cholesterol (LDL-C) had a significant positive correlation with age (r = 0.283, p < 0.018; r = 0.272, p < 0.023); TG was significantly positively correlated with systolic and diastolic blood pressure (r = 0.320. p < 0.007; r = 0.334, p < 0.005); HDL-C had a significant negative correlation with BMI, systolic and diastolic blood pressure (r = -0.252, p < 0.035; r = -0.29, p < 0.015; r = -0.329, p < 0.005). The lipid ratios (TC/HDL-C, LDL-C/HDL-C) were significantly positively correlated with body mass index (BMI), systolic and diastolic blood pressure. The Framingham Risk Score showed that only 2 subjects in the study group (4.4%) were at a high risk of having a cardiovascular event. CONCLUSION: Breast cancer patients have a higher prevalence of dyslipidaemia, and cardiovascular risk than the normal population.

Excessive fat expenditure in MCT-induced heart failure rats is associated with BMAL1/REV-ERBα circadian rhythmic loop disruption.

Fat loss predicts adverse outcomes in advanced heart failure (HF). Disrupted circadian clocks are a primary cause of lipid metabolic issues, but it's unclear if this disruption affects fat expenditure in HF. To address this issue, we investigated the effects of disruption of the BMAL1/REV-ERBα circadian rhythmic loop on adipose tissue metabolism in HF.50 Wistar rats were initially divided into control (n = 10) and model (n = 40) groups. The model rats were induced with HF via monocrotaline (MCT) injections, while the control group received equivalent solvent injections. After establishing the HF model, the model group was further subdivided into four groups: normal rhythm (LD), inverted rhythm (DL), lentivirus vector carrying Bmal1 short hairpin RNA (LV-Bmal1 shRNA), and empty lentivirus vector control (LV-Control shRNA) groups, each with 10 rats. The DL subgroup was exposed to a reversed light-dark cycle of 8 h: 16 h (dark: light), while the rest adhered to normal light-dark conditions (light: dark 12 h: 12 h). Histological analyses were conducted using H&E, Oil Red O, and Picrosirius red stains to examine adipose and liver tissues. Immunohistochemical staining, RT-qPCR, and Western blotting were performed to detect markers of lipolysis, lipogenesis, and beiging of white adipose tissue (WAT), while thermogenesis indicators were detected in brown adipose tissue (BAT). The LD group rats exhibited decreased levels of BMAL1 protein, increased levels of REV-ERBα protein, and disrupted circadian circuits in adipose tissue compared to controls. Additionally, HF rats showed reduced adipose mass and increased ectopic lipid deposition, along with smaller adipocytes containing lower lipid content and fibrotic adipose tissue. In the LD group WAT, expression of ATGL, HSL, PKA, and p-PKA proteins increased, alongside elevated mRNA levels of lipase genes (Hsl, Atgl, Peripilin) and FFA ß-oxidation genes (Cpt1, acyl-CoA). Conversely, lipogenic gene expression (Scd1, Fas, Mgat, Dgat2) decreased, while beige adipocyte markers (Cd137, Tbx-1, Ucp-1, Zic-1) and UCP-1 protein expression increased. In BAT, HF rats exhibited elevated levels of PKA, p-PKA, and UCP-1 proteins, along with increased expression of thermogenic genes (Ucp-1, Pparγ, Pgc-1α) and lipid transportation genes (Cd36, Fatp-1, Cpt-1). Plasma NT-proBNP levels were higher in LD rats, accompanied by elevated NE and IL-6 levels in adipose tissue. Remarkably, morphologically, the adipocytes in the DL and LV-Bmal1 shRNA groups showed reduced size and lower lipid content, while lipid deposition in the liver was more pronounced in these groups compared to the LD group. At the gene/protein level, the BMAL1/REV-ERBα circadian loop exhibited severe disruption in LV-Bmal1 shRNA rats compared to LD rats. Additionally, there was increased expression of lipase genes, FFA ß oxidation genes, and beige adipocyte markers in WAT, as well as higher expression of thermogenic genes and lipid transportation genes in BAT. Furthermore, plasma NT-proBNP levels and adipose tissue levels of NE and IL-6 were elevated in LV-Bmal1 shRNA rats compared with LD rats. The present study demonstrates that disruption of the BMAL1/REV-ERBα circadian rhythmic loop is associated with fat expenditure in HF. This result suggests that restoring circadian rhythms in adipose tissue may help counteract disorders of adipose metabolism and reduce fat loss in HF.

Microalgae to biodiesel: A novel green conversion method for high-quality lipids recovery and in-situ transesterification to fatty acid methyl esters.

Greenhouse gases (GHGs) emissions due to increasing energy demand have raised the need to identify effective solutions to produce clean and renewable energy. Biotechnologies are an effective platform to attain green transition objectives, especially when synergically integrated to promote health and environmental protection. In this context, microalgae-based biotechnologies are considered among the most effective tools for treating gaseous effluents and simultaneously capturing carbon sources for further biomass valorisation. The production of biodiesel is regarded as a promising avenue for harnessing value from residual algal biomass. Nonetheless, the existing techniques for extracting lipids still face certain limitations, primarily centred around the cost-effectiveness of the process.This study is dedicated to developing and optimising an innovative and cost-efficient technique for extracting lipids from algal biomass produced during gaseous emissions treatment based on algal-bacterial biotechnology. This integrated treatment technology combines a bio-scrubber for degrading gaseous contaminants and a photobioreactor for capturing the produced CO2 within valuable algal biomass. The cultivated biomass is then processed with the process newly designed to extract lipids simultaneously transesterificated in fatty acid methyl esters (FAME) via In Situ Transesterification (IST) with a Kumagawa-type extractor. The results of this study demonstrated the potential application of the optimised method to overcome the gap to green transition. Energy production was obtained from residuals produced during the necessary treatment of gaseous emissions. Using hexane-methanol (v/v = 19:1) mixture in the presence KOH in Kumagawa extractor lipids were extracted with extraction yield higher than 12% and converted in fatty acid methyl esters. The process showed the enhanced extraction of lipids converted in bio-sourced fuels with circular economy approach, broadening the applicability of biotechnologies as sustainable tools for energy source diversification.

Assessment of lipid layer patterns in domestic dogs and rabbits: an observational study.

Background: Maintaining a stable tear film is crucial for having healthy human and animal vision. Animals are expected to have thicker lipid layers than humans due to living in high-temperature and humid environments. Aim: The study aimed to evaluate the lipid layer patterns (LLPs) in Arabian dogs and rabbits using a non-invasive, practical, and easy-to-use device and compare them to humans with healthy eyes. Methods: The study included 75 domestic Arabian dogs (42 males and 33 females; mean ± SD = 6.1 ± 12.7 months) and 75 rabbits (37 males and 38 females; mean ± SD = 3.1 ± 3.4 months). In addition, 75 individuals with healthy eyes (39 males and 36 females; mean ± SD = 25.7 ± 5.0 years) were included for comparison. EASYTEAR View+ assessed the LLP in each animal's and individual's right eye. Results: The median LLP grades significantly differed between dogs and humans (Mann-Whitney U test, p < 0.001). Similarly, the LLP grades differed significantly between rabbits and humans (Mann-Whitney U test, p < 0.001). No significant difference (Mann-Whitney U test) in the LLP grades between dogs and rabbits was found. The analysis indicated that most dogs had either an A (34.7%) or a B grade (37.3%). Similarly, rabbits had predominantly A or 1 (46.7%) and B (30.7%) grades. On the other hand, humans had predominantly D (53.3%) and E (30.7%) grades. Conclusion: The EASYTEAR View+ has been employed to assess LLP in dogs and rabbits, and the measurements were compared to those of humans with normal ocular health. Dogs and rabbits have thinner lipid layers than healthy humans.

Turning waste into treasure: A new direction for low-cost production of lipid chemicals from Thraustochytrids.

Thraustochytrids are marine microorganisms known for their fast growth and ability to store lipids, making them useful for producing polyunsaturated fatty acids (PUFAs), biodiesel, squalene, and carotenoids. However, the high cost of production, mainly due to expensive fermentation components, limits their wider use. A significant challenge in this context is the need to balance production costs with the value of the end products. This review focuses on integrating the efficient utilization of waste with Thraustochytrids fermentation, including the economic substitution of carbon sources, nitrogen sources, and fermentation water. This approach aligns with the 3Rs principles (reduction, recycling, and reuse). Furthermore, it emphasizes the role of Thraustochytrids in converting waste into lipid chemicals and promoting sustainable circular production models. The aim of this review is to emphasize the value of Thraustochytrids in converting waste into treasure, providing precise cost reduction strategies for future commercial production.

Assessment of tear film parameters in females with refractive errors using a single device: An observational study.

This observational study aimed to evaluate the use of a single portable device to assess the non-invasive tear break-up time (NITBUT), tear meniscus height (TMH), and lipid layer patterns (LLP) in young females with refractive errors (REs). The study was conducted at the College of Applied Medical Science (Female campus), Riyadh, Saudi Arabia between January 5, 2021 to May 15, 2021. Forty young females, with mean age of 23.0± 4.3 years with REs (-2.53 ± 2.05 D) and 40 females, mean age 23.8± 4.5 years with healthy eyes were recruited. The tests were administered in the following order: Ocular Surface Disease Index (OSDI), followed by NITBUT, TMH, and LLP. Significant differences (via Mann-Whitney U test) were noted in the median ocular surface disease index (OSDI; p˂0.001), NITBUT (p=0.035), TMH (p=0.009), and LLP (p˂0.001) scores between the study and control groups. Females with REs have significantly lower lipid layer, TMH, and NITBUT scores than those with healthy eyes.

Establishment of pregnancy-specific lipid reference intervals in pregnant women in a single-centre and assessment of the predictive value of early lipids for gestational diabetes mellitus: a prospective cohort study.

INTRODUCTION: This study was aimed at establishing a pregnancy-specific lipid reference interval (RI) in pregnant women in a single-centre in the Beijing area of China, simultaneously exploring the predictive value of lipid levels in early pregnancy for gestational diabetes mellitus (GDM). MATERIAL AND METHODS: From October 2017 to August 2019, Peking University International Hospital established records for 1588 pregnant women, whose lipid profiles were determined during the first and third trimesters. The Hoffmann technique was used to calculate gestation-specific lipid RI. The 95% reference range for gestational lipids was also estimated for 509 healthy pregnant women screened according to the Clinical and Laboratory Standards Institute guideline. Multivariate logistic regression analysis was used to calculate odds ratios (OR) and their 95% confidence interval (CI), and the receiver operating characteristic (ROC) curve was applied to assess the predictive value of lipids in the first trimester for the diagnosis of GDM. RESULTS: Total cholesterol (TC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) levels were significantly higher in the third trimester (p < 0.05). Hoffmann technique RI of the lipid profiles and the 95% reference range of the lipid profiles in healthy pregnant women did not differ statistically (p > 0.05). TC, TG, and LDL-C levels were higher in the GDM group in the first trimester (p < 0.05), and the risk of GDM was 2.1 times higher in women with higher TG (95% CI: 1.13-3.77, p < 0.05). The optimal ROC cut-off for TG to predict GDM was 2.375 mmol / L, and the area under the ROC curve was 0.622 (95% CI: 0.592-0.751), with a sensitivity of 73.7% and a specificity of 59.3%. CONCLUSIONS: This study established pregnancy-specific lipid RI for pregnant women in a single centre in the Beijing area of China. Pregnant women with TG ≥ 2.375 mmol/L in the first trimester were at significantly increased risk for GDM.

Assessment of Serum Atherogenic Indices and Insulin Resistance in Retinal Vein Occlusion.

Objectives: This study aimed to investigate serum atherogenic indices as novel cardiovascular risk factors associated with retinal vein occlusion (RVO). Materials and Methods: This retrospective case-control study included 57 patients with newly diagnosed RVO whose plasma lipid profile (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglycerides [TG]) and insulin resistance were examined. Serum atherogenic indices (LDL-C/HDL-C, TC/HDL-C, TG/HDL-C, and non-HDL-C/HDL-C ratios) and presence of insulin resistance were compared between the patients and 63 healthy subjects. Cut-off values were determined by receiver operating characteristic curve analysis. Results: The mean age of the RVO patients was 63.7±9.4 years. Plasma levels of LDL-C, HDL-C, TC, and TG showed no significant difference between the patient and control groups (p>0.05). However, LDL-C/HDL-C, non-HDL-C/HDL-C, and TC/HDL-C ratios were higher in the RVO group compared to healthy subjects (p=0.015, p=0.036, and p=0.015, respectively). Fasting insulin concentrations, plasma insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index were higher in the RVO patients compared to controls (p=0.003, p=0.001, and p=0.001, respectively). Conclusion: LDL-C/HDL-C, TC/HDL-C, and non-HDL-C/HDL-C ratios were found to be increased in RVO. Compared to the traditional plasma lipid profile, serum atherogenic indices were found to be superior predictors of RVO development. Measurement of HOMA-IR index should be taken into consideration in the evaluation of insulin resistance. High serum atherogenic indexes in RVO patients reveal the need to take precautions against the risk of cardiovascular disease and stroke.

Comprehensive assessment of the effects of concurrent strength and endurance training on lipid profile, glycemic control, and insulin resistance in type 2 diabetes: A meta-analysis.

BACKGROUND: To investigate the effect of concurrent strength combined with endurance training on the lipid and glucose profile of type 2 diabetes mellitus (T2DM) using Meta-analysis. METHODS: The literature was searched from PubMed, Web of Science, EBSCO, and China National Knowledge Infrastructure(CNKI) databases for relevant randomized controlled trials with dates from the date of establishment to June 2023, and the included studies were individually assessed according to the Cochrane Risk of Bias tool in the Cochrane Systematic Assessor's Handbook, and the data were analyzed using RevMan 5.4 analysis software to analyze and process the data. RESULTS: A total of 9 articles were included, including 589 subjects, including 308 in the experimental group and 281 in the control group. The results of Meta analysis showed that concurrent strength combined with endurance training improved TC (SMD = -1.12, 95% CI = [-1.81, -0.44], P < 0.01), TG (SMD = -0.46, 95% CI = [-0.85, -0.07], P < 0.05), LDL-C (SMD = -1.3, 95% CI = [-2.09, -0.50], P < 0.01), HDL-C (SMD = 0.61, 95% CI = [0.05, 1.17], P < 0.05), FBG (SMD = -0.65, 95% CI = [-1.27, -0.04], P < 0.05), HOMA-IR (SMD = -1.23, 95% CI = [-2.40, -0.06], P < 0.05). CONCLUSION: Concurrent strength combined with endurance training has a positive effect on the improvement of lipid and glucose profile in patients with type 2 diabetes.

Assessment of functional efficacy of sheep plasma protein hydrolysates and their utilization in mutton sausage.

The present study examines the bioactive potential of sheep plasma protein hydrolysates (SPPH) produced by in-vitro gastrointestinal digestion as antioxidants, antimicrobials, anti-obesity agents, and inhibitors of lipid oxidation in sausage to address the oxidative stability and shelf-life issues of mutton. The antioxidant and antimicrobial activities, indicate a positive relationship between the degree of hydrolysis and digestion duration. The study finds that SPPH has a potent inhibitory effect on pancreatic lipase and cholesterol esterase. It has higher oil holding capacity than sheep plasma protein, observed at one hour of hydrolysis time. SPPH exhibit an improved behavior in foaming properties along alkaline pH and digestion time while display lower emulsifying activity and stability with hydrolysis advancement. The SPPH act as a natural preservative in developing functional mutton sausage by inhibiting lipid-oxidation. This study showed that the recovery of SPPH can be a cost-effective and sustainable strategy for generating available ingredients for enhanced shelf-life of meat products.

Lipid-coated nanocrystals of paclitaxel as dry powder for inhalation: Characterization, in-vitro performance, and pharmacokinetic assessment.

BACKGROUND: Nanocrystals can be produced as a dry powder for inhalation (DPIs) to deliver high doses of drug to the lungs, owing to their high payload and stability to the shear stress of aerosolization force. Furthermore, lipid-coated nanocrystals can be formulated to improve the drug accumulation and retention in lung. OBJECTIVE: The present work involved the fabrication of paclitaxel nanocrystals using hydrophilic marine biopolymer fucoidan as a stabilizer. Thereafter, fabricated nanocrystals (FPNC) were surface-modified with phospholipid to give lipid-coated nanocrystals (Lipo-NCs). METHODS: The nanocrystals were fabricated by antisolvent crystallization followed by the probe sonication. The lipid coating was achieved by thin film hydration followed ultrasonic dispersion technique. Prepared nanocrystals were lyophilized to obtain a dry powder of FPNC and Lipo-NCs, used later for physicochemical, microscopic, and spectroscopic characterization to confirm the successful formation of desired nanocrystals. In-vitro and in-vivo investigations were also conducted to determine the role of nanocrystal powder in pulmonary drug delivery. RESULTS: Lipo-NCs exhibited slower drug release, excellent flow properties, good aerosolization performance, higher drug distribution, and prolonged retention in the lungs compared to FPNC and pure PTX. CONCLUSION: Lipid-coated nanocrystals can be a novel formulation for the maximum localization of drugs in the lungs, thereby enhancing therapeutic effects and avoiding systemic side effects in lung cancer therapy.

Lipid Association of India 2023 update on cardiovascular risk assessment and lipid management in Indian patients: Consensus statement IV.

OBJECTIVE: In 2016, the Lipid Association of India (LAI) developed a cardiovascular risk assessment algorithm and defined low-density lipoprotein cholesterol (LDL-C) goals for prevention of atherosclerotic cardiovascular disease (ASCVD) in Indians. The recent refinements in the role of various risk factors and subclinical atherosclerosis in prediction of ASCVD risk necessitated updating the risk algorithm and treatment goals. METHODS: The LAI core committee held twenty-one meetings and webinars from June 2022 to July 2023 with experts across India and critically reviewed the latest evidence regarding the strategies for ASCVD risk prediction and the benefits and modalities for intensive lipid lowering. Based on the expert consensus and extensive review of published data, consensus statement IV was commissioned. RESULTS: The young age of onset and a more aggressive nature of ASCVD in Indians necessitates emphasis on lifetime ASCVD risk instead of the conventional 10-year risk. It also demands early institution of aggressive preventive measures to protect the young population prior to development of ASCVD events. Wide availability and low cost of statins in India enable implementation of effective LDL-C-lowering therapy in individuals at high risk of ASCVD. Subjects with any evidence of subclinical atherosclerosis are likely to benefit the most from early aggressive interventions. CONCLUSIONS: This document presents the updated risk stratification and treatment algorithm and describes the rationale for each modification. The intent of these updated recommendations is to modernize management of dyslipidemia in Indian patients with the goal of reducing the epidemic of ASCVD among Indians in Asia and worldwide.

Physical characterization and bioavailability assessment of 5-fluorouracil-based nanostructured lipid carrier (NLC): In vitro drug release, Hemolysis, and permeability modulation.

5-Fluorouracil (5-FU) is an anticancer agent belonging to BCS Class III that exhibits poor release characteristics and low retention in the biological system. The main objective of this investigation was to develop a drug delivery system, i.e., Nanostructure Lipid Carriers (NLCs) loaded with 5-FU to prolong its biological retention through 5-FU-loaded NLCs (5-FUNLC) were designed to manipulate physicochemical characteristics and assessment of in vitro and in vivo performance. The developed NLCs underwent comprehensive characterization, including assessments for particle size, zeta potential, morphological evaluation, and FT-IR spectroscopy. Additionally, specific evaluations were conducted for 5-FUNLCs, encompassing analyses for encapsulation efficiency of the drug, release characteristics in PBS at pH 6.8, and stability study. The lipophilic character of 5-FUNLC was confirmed through the measurement of the partition coefficient (log P). 5-FUNLCs were observed as spherical-shaped particles with a mean size of 300 ± 25 nm. The encapsulation efficiency was determined to be 89%, indicating effective drug loading within the NLCs. Furthermore, these NLCs exhibited a sustained release nature lasting up to 3-4 h, indicating their potential for controlled drug release over time. Lipid components were biocompatible with the 5-FU to determine thermal transition temperature and show good stability for 30 days. Additionally, an in vitro hemolysis study that confirmed the system did not cause any destruction to the RBCs during intravenous administration. The drug's gut permeability was assessed utilizing the optimized 5-FUNLC (F2) in comparison to 5-FU through the intestine or gut sac model (in the apical to basolateral direction, A → B). The permeability coefficient was measured as 4.91 × 10-5 cm/h with a significant difference. Additionally, the antioxidant potential of the NLCs was demonstrated through the DPPH method. The NLCs' performance was further assessed through in vivo pharmacokinetic studies on Wistar Rats, resulting in a 1.5-fold enhancement in their activity compared to free 5-FU. These NLCs offer improved drug solubility and sustained release, which collectively contribute to enhanced therapeutic outcomes and modulate bioavailability. The study concludes by highlighting the potential of 5-FUNLC as an innovative and efficient drug delivery system. The findings suggest that further preclinical investigations are warranted, indicating a promising avenue for the development of more effective and well-tolerated treatments for cancer.

Development of solid lipid microparticles (SLMs) containing asiatic acid for topical treatment of acne: Characterization, stability, in vitro and in vivo anti-acne assessment.

Solid lipid microparticles (SLMs) represent a promising approach for drug delivery in anti-acne applications. In this study, asiatic acid-loaded SLMs (AASLMs) were prepared by melt emulsification method in conjunction with freeze-drying. Comprehensive evaluations comprised particle size, %entrapment efficiency (%EE), %labeled amount (%LA), surface morphology, stability, %release, %skin permeation, and anti-acne activity. The AASLMs exhibited an average particle size ranging from 7.46 to 38.86 µm, with %EE and %LA falling within the range of 31.56 to 100.00 and 90.43 to 95.38, respectively. The AASLMs demonstrated a spherical shape under scanning electron microscopy, and maintained stability over a 3-month period. Notably, formulations with 10 % and 15 % cetyl alcohol stabilized with poloxamer-188 (specifically F6 and F12) displayed a minimum inhibitory concentration (MIC) value of 75 mg/ml against Cutibacterium acnes. Furthermore, F12 exhibited a higher %release and %skin permeation compared to F6 over 24 h. In a single-blind clinical trial involving fifteen participants with mild-to-moderate acne, F12 showcased its potential not only in reducing porphyrin intensity and enhancing skin barriers but also in significantly improving skin hydration and brightness. However, further investigations with larger subject cohorts encompassing diverse age groups and genders are necessary to thoroughly establish the performance of the developed AASLMs.

Alisol B 23-acetate promotes white adipose tissue browning to mitigate high-fat diet-induced obesity by regulating mTOR-SREBP1 signaling.

OBJECTIVE: Obesity is a global health concern with management strategies encompassing bariatric surgery and anti-obesity drugs; however, concerns regarding complexities and side effects persist, driving research for more effective, low-risk strategies. The promotion of white adipose tissue (WAT) browning has emerged as a promising approach. Moreover, alisol B 23-acetate (AB23A) has demonstrated efficacy in addressing metabolic disorders, suggesting its potential as a therapeutic agent in obesity management. Therefore, in this study, we aimed to investigate the therapeutic potential of AB23A for mitigating obesity by regulating metabolic phenotypes and lipid distribution in mice fed a high-fat diet (HFD). METHODS: An obesity mouse model was established by administration of an HFD. Glucose and insulin metabolism were assessed via glucose and insulin tolerance tests. Adipocyte size was determined using hematoxylin and eosin staining. The expression of browning markers in WAT was evaluated using Western blotting and quantitative real-time polymerase chain reaction. Metabolic cage monitoring involved the assessment of various parameters, including food and water intake, energy metabolism, respiratory exchange rates, and physical activity. Moreover, oil red O staining was used to evaluate intracellular lipid accumulation. A bioinformatic analysis tool for identifying the molecular mechanisms of traditional Chinese medicine was used to examine AB23A targets and associated signaling pathways. RESULTS: AB23A administration significantly reduced the weight of obese mice, decreased the mass of inguinal WAT, epididymal WAT, and perirenal adipose tissue, improved glucose and insulin metabolism, and reduced adipocyte size. Moreover, treatment with AB23A promoted the expression of browning markers in WAT, enhanced overall energy metabolism in mice, and had no discernible effect on food intake, water consumption, or physical activity. In 3T3-L1 cells, AB23A inhibited lipid accumulation, and both AB23A and rapamycin inhibited the mammalian target of rapamycin-sterol regulatory element-binding protein-1 (mTOR-SREBP1) signaling pathway. Furthermore, 3-isobutyl-1-methylxanthine, dexamethasone and insulin, at concentrations of 0.25 mmol/L, 0.25 µmol/L and 1 µg/mL, respectively, induced activation of the mTOR-SREBP1 signaling pathway, which was further strengthened by an mTOR activator MHY1485. Notably, MHY1485 reversed the beneficial effects of AB23A in 3T3-L1 cells. CONCLUSION: AB23A promoted WAT browning by inhibiting the mTOR-SREBP1 signaling pathway, offering a potential strategy to prevent obesity. Please cite this article as: Han LL, Zhang X, Zhang H, Li T, Zhao YC, Tian MH, Sun FL, Feng B. Alisol B 23-acetate promotes white adipose tissue browning to mitigate high-fat diet-induced obesity by regulating mTOR-SREBP1 signaling. J Integr Med. 2024; 22(1): 83-92.

Computational Assessment of the Biocompatibility of Two-Dimensional g-C3N3 Toward Lipid Membranes.

One of the most recent additions to the family of two-dimensional (2D) materials, graphitic C3N3 (g-C3N3), has been considered a viable contender for biomedical applications, although its potential toxicity remains elusive. We perform all-atom molecular dynamics simulations to decipher the interactions between model lipid membranes and g-C3N3 as a first step toward exploring the cytotoxicity induced at the nanoscale. We show that g-C3N3 can easily insert into the cellular membranes following a multistage mechanism consisting of simultaneous desolvation of the 2D material along with enrichment of nanomaterial-lipid interactions. Free energy calculations indicate that g-C3N3 is more stable in a membrane-bound state compared to an aqueous solution; however, the insertion of the material does not disturb the structural integrity of lipid membranes. After being inserted into a membrane, g-C3N3 is unlikely to be released into the cellular environment and is incapable of extracting lipid molecules from the membrane. The nature of interaction between the 2D material and membranes is found to be independent of the nanomaterial size. Also, the performance of g-C3N3 toward biomolecular delivery is shown to be significantly improved compared to the state-of-the-art 2D materials graphene and hexagonal boron nitride (h-BN). It is revealed that, the affinity of g-C3N3 toward lipid membranes is weaker compared to the nanotoxic graphene and h-BN, while being marginally higher than h2D-C2N, which in turn, increases the biocompatibility of the material, thereby brightening its future as a noncytotoxic material for forthcoming biomedical applications.