Fine-tuning the activation behaviors of ternary modular cabazitaxel prodrugs for efficient and on-target oral anti-cancer therapy.

The disulfide bond plays a crucial role in the design of anti-tumor prodrugs due to its exceptional tumor-specific redox responsiveness. However, premature breaking of disulfide bonds is triggered by small amounts of reducing substances (e.g., ascorbic acid, glutathione, uric acid and tea polyphenols) in the systemic circulation. This may lead to toxicity, particularly in oral prodrugs that require more frequent and high-dose treatments. Fine-tuning the activation kinetics of these prodrugs is a promising prospect for more efficient on-target cancer therapies. In this study, disulfide, steric disulfide, and ester bonds were used to bridge cabazitaxel (CTX) to an intestinal lymph vessel-directed triglyceride (TG) module. Then, synthetic prodrugs were efficiently incorporated into self-nanoemulsifying drug delivery system (corn oil and Maisine CC were used as the oil phase and Cremophor EL as the surfactant). All three prodrugs had excellent gastric stability and intestinal permeability. The oral bioavailability of the disulfide bond-based prodrugs (CTX-(C)S-(C)S-TG and CTX-S-S-TG) was 11.5- and 19.1-fold higher than that of the CTX solution, respectively, demonstrating good oral delivery efficiency. However, the excessive reduction sensitivity of the disulfide bond resulted in lower plasma stability and safety of CTX-S-S-TG than that of CTX-(C)S-(C)S-TG. Moreover, introducing steric hindrance into disulfide bonds could also modulate drug release and cytotoxicity, significantly improving the anti-tumor activity even compared to that of intravenous CTX solution at half dosage while minimizing off-target adverse effects. Our findings provide insights into the design and fine-tuning of different disulfide bond-based linkers, which may help identify oral prodrugs with more potent therapeutic efficacy and safety for cancer therapy.

Alkylphthalides with intracellular triglyceride metabolism-promoting activity from the rhizomes of Cnidium officinale Makino.

Methanol extract of the Cnidium officinale Makino rhizome, which is used as a crude drug Cnidium Rhizome (Cnidii Rhizoma; "Senkyu" in Japanese) and is listed in the Japanese Pharmacopoeia XVIII, showed intracellular triglyceride metabolism-promoting activity in high glucose-pretreated HepG2 cells. Thirty-five constituents, including two new alkylphthalide glycosides, senkyunosides A (1) and B (2), and a neolignan with a new stereoisomeric structure (3), were isolated in the extract. Their stereostructures were elucidated based on chemical and spectroscopic evidence. Among the isolates, several alkylphthalides, (Z)-3-butylidene-7-methoxyphthalide (9) and senkyunolides G (10), H (14), and I (15), and a polyacetylene falcarindiol (26), were found to show significant activity without any cytotoxicity at 10 µM.

Exploring the dietary and therapeutic potential of licorice (Glycyrrhiza uralensis Fisch.) sprouts.

ETHNOPHARMACOLOGICAL RELEVANCE: This research substantiates the traditional use of Glycyrrhiza uralensis Fisch. for liver health, with scientific evidence of the non-toxic and lipid-lowering properties of licorice sprout extracts. The sprouts' rich mineral and amino acid content, along with their strong antioxidant activity, reinforce their value in traditional medicine. These findings bridge ancient herbal practices with modern science, highlighting licorice's potential in contemporary therapeutic applications. AIM OF THE STUDY: The study aimed to investigate the dietary and medicinal potential of G. uralensis sprouts by assessing their safety, nutritional content, and antioxidant properties using both plant and animal models. Specifically, the study sought to determine the effects of different sizes of licorice sprouts on lipid metabolism in human liver cancer cells and their overall impact on rat health indicators. MATERIALS AND METHODS: The study examined the effects of aqueous and organic extracts from G. uralensis sprouts of varying lengths on the cytotoxicity, lipid metabolism, and antioxidant activity in HepG2 cells, alongside in vivo impacts on Sprague-Dawley rats, using MTT, ICP, and HPLC. It aimed to assess the potential health benefits of licorice sprouts by analyzing their protective effects against oxidative stress and their nutritional content. RESULTS: Licorice sprout extracts from G. uralensis demonstrated no cytotoxicity in HepG2 cells, significantly reduced lipid levels, and enhanced antioxidant activities, with the longest sprouts (7 cm) showing higher mineral, sugar, and arginine content as well as increased glycyrrhizin and liquiritigenin. In vivo studies with Sprague-Dawley rats revealed weight gain and improved antioxidant enzyme activities in blood plasma and liver tissues after consuming the extracts, highlighting the sprouts' dietary and therapeutic potential. CONCLUSIONS: This study is the first to demonstrate that G. uralensis sprouts, particularly those 7 cm in length, have no cytotoxic effects, reduce lipids, and have high mineral and antioxidant contents, offering promising dietary and therapeutic benefits.

Effects of coffee and tea on postprandial cardiometabolic risk factors in healthy individuals: a randomized crossover trial.

BACKGROUND AND OBJECTIVES: The effect of different coffee and tea consumption on postprandial glucose and lipid metabolism has never been reported previously. The aim of the present study was to investigate the effect of different coffee or tea consumption at breakfast on postprandial cardiometabolic risk factors in healthy individuals. METHODS AND STUDY DESIGN: Eighteen healthy young subjects completed the trial. After 8-hour overnight fast, volunteers either ingested water, freeze-dried coffee, spray-dried coffee, green tea, black tea or oolong tea together with a breakfast consisting of an egg and 180g deep-fried dough sticks. Blood was drawn at 0h, 0.5h, 1h, 2h, and 3h. RESULTS: The differences in triglyceride (TG) values relative to the baseline levels at 2h and 3h of green tea was significantly decreased compared with black tea and oolong tea (p<0.05). Compared with black tea, green tea and oolong tea significantly reduced postprandial total cholesterol (TC) levels (p<0.05, p<0.01), respectively. Furthermore, the serum concentrations of high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) were substantially decreased after oolong tea consumption compared with black tea (p<0.05, p<0.01). CONCLUSIONS: Green tea ingestion can lower the elevation of serum TG and TC levels after high-fat or high-cholesterol diets. Our findings have far-reaching implications given the widespread use of coffee and tea and the current concern over cardiometabolic risk factors.

Meta-analysis of the intervention effects of tai chi on fasting blood glucose, blood pressure and triglyceride in middle-aged and elderly people.

BACKGROUND: Hypertension, hyperlipidemia, and hyperglycemia have emerged as global health concerns of paramount significance. With the burgeoning popularity of mind-body therapy, cardiovascular patients have increasingly exhibited a vested interest in the practice of Tai Chi. The objective of this study seeks to quantitatively assess the impact of Tai Chi interventions on blood pressure, lipid levels, and glucose concentrations among the elderly population, thereby explaining the optimal intervention protocol. METHODS: An extensive search was conducted across multiple databases, including Web of Science, PubMed, CNKI, WANFANG DATA, RISS, KISS, and DBPIA, comprising English, Korean, and Chinese literature. The search strategy employed a retrieval method of subject term 1 + subject term 2, which included both full names and abbreviations of the terms. Specifically, "taijiquan" or "Tai Chi" were set as the Term 1, while Term 2 was set as "blood pressure," "BP," "Fasting blood glucose," "FBG," "Triglyceride," and "TG." Thereafter, the retrieved articles were filtered in accordance with the PICOS method. Risk of bias assessment was performed using RoB 2.0, while data analysis was conducted using Comprehensive Meta-Analysis 3.7. RESULTS: A total of 57 studies, including 3,856 research subjects, were eligible for inclusion. The findings of the primary effect quantitative synthesis demonstrated that Tai Chi exerted an improvement on systolic blood pressure (SBP) (ES = -0.764, p < .001), diastolic blood pressure (DBP) (ES = -0.426, p = .001), triglyceride (TG) (ES = -0.452, p < .001), and fasting blood glucose concentrations (FBG) (ES = -0.552, p = .002) among middle-aged and elderly individuals. Subgroup analysis further revealed that the intervention effects were significantly influenced by the characteristics of the research subjects and the specific intervention protocol employed. CONCLUSION: Tai Chi, as a gentle form of aerobic exercise, exerts a profound impact on reducing blood pressure, fasting blood glucose levels, and triglyceride concentrations among middle-aged and elderly individuals. Notably, the intervention effect is particularly pronounced among male patients afflicted with hypertension, hyperglycemia, and hyperlipidemia. Based on the collective advantages underscored by this research, we strongly recommend engaging in Tai Chi exercises for a minimum duration of 16 weeks, with each session lasting 30-50 min and conducted 6-7 times per week, without any restrictions on the style employed.

Eight weeks of daily cottonseed oil intake attenuates postprandial angiopoietin-like proteins 3 and 4 responses compared to olive oil in adults with hypercholesterolemia: A secondary analysis of a randomized clinical trial.

Angiopoietin-like proteins (ANGPTLs) -3, -4, and -8 are regulators of lipid metabolism and have been shown to respond to changes in dietary fats. It is unknown how ANGPTLs respond to cottonseed oil (CSO) and olive oil (OO) consumption in a population with hypercholesterolemia. The purpose of this study was to determine the impact of CSO vs. OO consumption on fasting and postprandial ANGPTL responses in adults with hypercholesterolemia. We hypothesized that CSO would have lower fasting and postprandial ANGPTL responses compared with OO. Forty-two adults with high cholesterol completed a single-blind, randomized trial comparing CSO (n = 21) vs. OO (n = 21) diet enrichment. An 8-week partial outpatient feeding intervention provided ∼60% of the volunteers' total energy expenditure (∼30% of total energy expenditure as CSO or OO). The remaining 40% was not controlled. Fasting blood draws were taken at pre-, mid-, and postintervention visits. Volunteers consumed a high saturated fat meal followed by 5 hours of blood draws pre- and postvisits. Fasting ANGPTL3 had a marginally significant treatment by visit interaction (P = .06) showing an increase from pre- to postintervention in CSO vs. OO (CSO: 385.1 ± 27.7 to 440.3 ± 33.9 ng/mL; OO: 468.2 ± 38.3 to 449.2 ± 49.5 ng/mL). Both postprandial ANGPTL3 (P = .02) and ANGPTL4 (P < .01) had treatment by visit interactions suggesting increases from pre- to postintervention in OO vs. CSO with no differences between groups in ANGPTL8. These data show a worsening (increase) of postprandial ANGPTLs after the OO, but not CSO, intervention. This aligns with previously reported data in which postprandial triglycerides were protected from increases compared with OO. ANGPTLs may mediate protective effects of CSO consumption on lipid control. This trial was registered at clinicaltrials.gov (NCT04397055).

Interplay of Postprandial Triglyceride-Rich Lipoprotein Composition and Adipokines in Obese Adolescents.

In the context of the alarming rise of infant obesity and its health implications, the present research aims to uncover disruptions in postprandial lipid metabolism and the composition of triglyceride-rich lipoproteins in obese adolescents. A double-blind, controlled clinical trial in the postprandial phase on 23 adolescents aged 12 to 16 years was carried out. Twelve participants were categorized as obese (BMI > 30 kg/m2 and percentile > 95) and 11 as normal-weight (BMI = 20-25 kg/m2, percentile 5-85). Blood samples were collected after a 12-h overnight fast and postprandially after consumption of a standardized breakfast containing olive oil, tomato, bread, orange juice, and skimmed milk. Obese adolescents exhibited elevated triglyceride concentrations in both fasting and postprandial states and higher TG/apo-B48 ratios, indicating larger postprandial triglyceride-rich lipoprotein (TRL) particle size, which suggests impaired clearance. Obese subjects also exhibited higher n-6 PUFA concentrations, potentially linked to increased TRL hydrolysis and the release of pro-inflammatory adipokines. In contrast, TRL from normal-weight individuals showed higher concentrations of oleic acid and DHA (n-3 PUFA), with possible anti-inflammatory effects. The results indicate an interplay involving postprandial TRL metabolism and adipokines within the context of adolescent obesity, pointing to potential cardiovascular implications in the future.

Regulating microsomal triglyceride transfer protein with natural products for the treatment of hyperlipidaemia.

Hyperlipidaemia, characterised by elevated levels of lipids, particularly LDL-C, is a significant risk factor for atherosclerotic cardiovascular disease. While synthetic inhibitors of microsomal triglyceride transfer protein (MTP) have shown potential in lowering LDL-C, they are associated with adverse effects. This study explores a novel approach by screening natural products to identify plant extracts that down-regulate MTP gene expression, aiming to reduce hyperlipidaemia with fewer side effects. Modulating MTP expression, rather than direct inhibition, offers a promising avenue for lowering plasma lipids and mitigating cardiovascular risk. Various plant extracts were examined for their potential as MTP down-regulators, with Liquorice root and Pomegranate rind extracts demonstrating the highest efficacy. Additionally, the study assessed the total phenolic content of these extracts, revealing their -antioxidant capacity. This research provides a foundation for further investigation into bioactive molecules as potential anti-hyperlipidemic agents with improved safety profiles, addressing a critical need in cardiovascular disease prevention.

Selenium Concentration Is Positively Associated with Triglyceride-Glucose Index and Triglyceride Glucose-Body Mass Index in Adults: Data from NHANES 2011-2018.

Compiling evidence supports that selenium plays a vital role in glucose metabolism. Triglyceride-glucose index (TyG) and triglyceride-glucose-body mass index (TyG-BMI) are commonly used in epidemiologic studies to evaluate insulin resistance and cardiovascular disease (CVD) risks. This study is aimed to investigate the association between whole blood selenium concentration and TyG and TyG-BMI. A total of 6290 participants (age ≥ 20 years) from the National Health and Nutrition Examination Survey (NHANES) 2011-2018 were included. Multiple linear regression models were used to examine the association between blood selenium quartiles and TyG and TyG-BMI. Subgroup analysis stratified by diabetes status was also performed. The adjusted model showed a positive association between TyG and blood selenium concentration (ß [95%CI] = 0.099 [0.063, 0.134], p < 0.001) and TyG-BMI (ß [95%CI] = 3.185 [2.102, 4.268], p < 0.001). The association persisted after stratification by diabetes status (p < 0.001). Participants were stratified into four quartiles based on selenium concentration (Q1: 1.08-2.24 µmol/L, Q2: 2.25-2.42 µmol/L, Q3: 2.43-2.62 µmol/L, Q4: 2.63-8.08). Compared with the Q1 group, TyG in the Q3 and Q4 groups was significantly higher (ß = 0.075 [95%CI 0.039 to 0.112] and ß = 0.140 [95%CI 0.103 to 0.176], respectively). Additionally, TyG-BMI in the Q2, Q3, and Q4 groups was higher than that in the Q1 group (ß = 1.189 [95%CI 0.065 to 2.314], ß = 2.325 [95%CI 1.204 to 3.446], and ß = 4.322 [95%CI 3.210 to 5.435], respectively). Blood level of selenium was positively associated with TyG and TyG-BMI, indicating that excessive blood selenium may be associated with impaired insulin sensitivity and increased risk of cardiovascular disease.

High dietary intake of unsaturated fatty acids is associated with improved insulin resistance - a cross-sectional study based on the NHANES database.

BACKGROUND: A moderate intake of unsaturated fatty acids (UFA) is associated positively with improved insulin resistance. The aim of this study was to investigate the relationship between the dietary intake of unsaturated fatty acids/total fats (UFA/TF) and insulin resistance. METHODS: 15,560 participants were selected from the National Health and Nutrition Examination Survey (NHANES) database enrolled between March 2017 and 2020, and excluded those under 20 years of age, pregnant, or with missing data for key research items. Finally, 7,630 participants were included in the study. R software was used for data analysis that included: (1) general descriptive statistics; (2) comparison of differences in baseline information of three UFA/TF groups, namely low, medium, and high ratios; (3) calculation of the correlation between the UFA/TF ratio and markers of insulin resistance: triglyceride-glucose index (TyG) and homeostatic model assessment for insulin resistance (HOMA-IR); (4) stratification of the study subjects into two groups, with or without insulin resistance, using a cut-off value of HOMA-IR ≥ 2, followed by logistic regression analysis to examine the relationship between UFA/TF and insulin resistance status in the two groups; and (5) further stratification of the subjects according to age, gender, body mass index (BMI), race, total energy intake, total protein, total carbohydrate, total sugars, total dietary fiber, total fat, alcohol consumption, diabetes, hypercholesterolemia to analyze the impact of UFA/TF on insulin resistance status in different subgroups. RESULTS: (1) A high UFA/TF level was associated with a low TyG index and HOMA-IR [ß (vs. TyG index) = -0.559, 95% CI: (-0.821~-0.297), P < 0.001; ß (vs. HOMA-IR) = -0.742, 95% CI: (-1.083~-0.402), P < 0.001]. This negative relationship became more pronounced when UFA/TF exceeded 57.9% (i.e., the higher group). (2) Logistic regression analysis showed that a higher UFA/TF level was associated with a lower risk of developing insulin resistance [Q3 vs. Q1: 0.838 (95%CI: 0.709 ~ 0.991); P for trend = 0.038]. After adjusting for covariates such as gender, age, and BMI, this protective effect remained significant (P value < 0.05). (3) Analysis also showed that increased UFA/TF intake reduced the risk of developing insulin resistance (OR = 0.266, 95% CI: (0.075 ~ 0.946), P = 0.041). Subgroup analysis showed that although elevated UFA/TF intake showed no statistically significant difference in its effect in most subgroups, the large study population in this study provides valuable insights on potential changes. Increased UFA/TF intake may confer relatively greater benefits within specific subgroups, particularly among the elderly [Q3 age group, OR = 0.114, 95%CI: (0.012 ~ 1.078), P = 0.058], females [OR = 0.234, 95%CI: (0.041 ~ 1.333), P = 0.102], those with a BMI ≤ 25 kg/m²[OR = 0.191, 95%CI: (0.016 ~ 2.344), P = 0.196], and individuals without hypercholesterolemia [OR = 0.207, 95%CI: (0.042 ~ 1.013), P = 0.0519]. The impact of high UFA/TF levels within subgroups based on the presence or absence of coronary heart disease and stroke displayed contrasting trends. In those without coronary heart disease, there was a significant protective effect against insulin resistance [OR = 0.254, 95% CI: (0.07 ~ 0.929), P = 0.0384], while in the stroke subgroup, a significantly protective effect against insulin resistance was observed [OR = 0.002, 95%CI: (0 ~ 0.695), P = 0.0376]. CONCLUSION: A high dietary intake of UFA relative to total fat consumption could be a protective factor against the risk of developing insulin resistance.

Medium-chain triglycerides (8:0 and 10:0) increase muscle mass and function in frail older adults: a combined data analysis of clinical trials.

Background: Three clinical trials have examined the chronic effects of medium-chain triglycerides (MCTs) on muscle mass and function in frail older adults (mean age 85 years old). However, significant increases in muscle mass and some muscle function relative to long-chain triglycerides (LCTs) have yet to be shown, possibly due to the small number of participants in each trial. Objective: We re-analyzed these previous clinical trials to clarify whether MCT supplementation can increase muscle mass and function. Analysis: After adding post hoc tests to the original report, we compared changes in measurement between the MCT and LCT groups in the first 2 trials and conducted a combined data analysis. Methods: In a combined data analysis, changes from baseline in measurements at the 3 months intervention in the MCTs- and LCTs-containing groups were assessed by analysis of covariance adjusted for baseline values of each measurement, age, sex, BMI, allocation to trial, habitual intakes in energy, protein, leucine, octanoic acid, decanoic acid, and vitamin D during the baseline period. The Mann-Whitney U test was used to analyze data on right and left knee extension times. Results: MCT supplementation for 3 months increased muscle function relative to LCT supplementation with and without an L-leucine (1.2 g) and vitamin D (cholecalciferol, 20 µg)-enriched supplement. In a combined data analysis (n = 29 in MCTs, n = 27 in LCTs), relative to supplementation with 6 g LCTs/day, supplementation with 6 g MCTs/day at dinner for 3 months significantly increased body weight (adjusted mean change from baseline: MCTs 1.2 vs. LCTs 0.2 kg, p = 0.023), right arm muscle area (MCTs 1.4 vs. LCTs-0.7 cm2, p = 0.002), left calf circumference (p = 0.015), right-hand grip strength (MCTs 1.6 vs. LCTs 0.3 kg, p = 0.017), right knee extension time (p = 0.021), left knee extension time (p = 0.034), walking speed (p = 0.002), and number of iterations in leg open and close test (p < 0.001) and decreased right triceps skinfold thickness (p = 0.016). Conclusion: In frail older adults, supplementation for 3 months with a low dose (6 g/day) of MCTs (C8:0 and C10:0) increased muscle mass and function. These findings indicate the potential for the practical use of MCTs in daily life in treating sarcopenia.

Effectiveness of the Combination of Probiotic Supplementation on Motor Symptoms and Constipation in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) reflects the second most common neurodegenerative disorder and is associated with high morbidity and mortality. Besides the motor features, non-motor symptoms, such as constipation, are very common. There is accumulating evidence that neuroinflammation is associated with the PD pathological processes. Alterations of gut microbiota and microbial metabolites have been linked to the pathogenesis of PD. Previous research has shown that probiotic supplementation has beneficial effects on motor and non-motor symptoms and especially on constipation. AIM: In this study, we examine the effectiveness of a combination of probiotic supplementation (butyrate triglyceride 302.86 mg, Crocus sativus L. 30 mg, and vitamin D3 100 mcg), on constipation and motor symptoms in PD. METHODS: The present study is a retrospective study that examined the existing medical records of patients with diagnosed PD, having chronic constipation and used the probiotic supplementation for its management. A total of 41 existing medical records were screened. Medical records were excluded in the case of participation in another study for PD, suffering from irritable bowel syndrome, organic constipation, long-term laxative use changes in the standard dopaminergic treatment, Mini-Mental Status Examination (MMSE) score<24, hospitalization and antibiotic medication, and diarrheal syndrome. Nine medical records were excluded, and a final number of 32 medical records was finally examined. All 32 patients had evaluations carried out at baseline and three months after supplement administration. A stool diary questionnaire, the Unified Parkinson's Disease Rating Scale III (UPDRS III), and the Schwab and England and the Hoehn and Yahr scales were used for the evaluation. RESULTS: The median defecation frequency was significantly improved. The supplementation administration significantly improved UPDRS III by 7.7% (from 35.72±15.51 to 32.97±15.71, p = 0.005) at month three, as compared to baseline. A positive effect was also seen in the Schwab and England scale. There was no effect on the Hoehn and Yahr scale. CONCLUSION: The enteric microbiome composition is altered in PD, and there is accumulating evidence that probiotic supplementation could alleviate disease symptoms in neuroinflammatory disorders.

Anthocyanin-enriched extract from Ribes nigrum inhibits triglyceride and cholesterol accumulation in adipocytes.

Aim: Obesity is a chronic pathology of epidemic proportions. Mature adipocytes from a 3T3-L1 cell line were used as in vitro obesity model to test different bioactive compounds. We aim to evaluate cassis (Ribes nigrum) extract antioxidant activity and its antiadipogenic effect on mature adipocytes. Results: We produced an extract by using enzyme that combines cellulase and pectinase; we obtained high yield of the bioactive compound anthocyanin. Extract showed high antioxidant capacity. We conducted in vitro assays by adding the extract to adipocytes culture medium. Extract reduced intracellular levels of triglyceride by 62% and cholesterol by 32%. Conclusion: Enzymatic extract's high antioxidant activity was likely attributable to its high concentration of anthocyanin. This extract inhibits lipid accumulation in adipocytes.

Obesity is a disease all over the world. By 2030, nearly 20% of adults are predicted to be obese. The consumption of processed foods is related to obesity in some countries such as Argentina. More natural food is needed. There are many different anti-obesity medicines but there is no good one to lose weight. We took extracts from cassis fruits and tested whether they could decrease fats like cholesterol within fat cells. We found that these extracts could successfully reduce the fat levels in the cells. Our results indicate that natural compounds like cassis fruit extract may be helpful in preventing future obesity epidemics.

Effects of Indonesian Shortfin Eel (Anguilla bicolor) By-Product Oil Supplementation on HOMA-IR and Lipid Profile in Obese Male Wistar Rats.

The prevalence of people being overweight and obese has increased globally over the past decades. The use of omega-3 fatty acids-a compound usually primarily found in fish oil-has been known to improve the metabolic profile of obese patients. As the demand for eels increases, the number of waste products from the eels increases and creates environmental problems. This study was conducted to investigate the effect of a newly discovered Indonesian Shortfin eel by-product oil supplementation on the Homeostasis Model Assessment-Estimated Insulin Resistance (HOMA-IR) and lipid profiles of obese male (Lee index ≥ 0.3) Wistar rats (Rattus norvegicus). The oil was extracted from waste products (heads). Fifteen obese rats were divided into three groups and were administered NaCl (C), commercial fish oil (CO), and Indonesian shortfin eel by-product oil (EO). All groups had statistically significant differences in total cholesterol, LDL, and triglyceride levels (p < 0.05). The CO and EO group showed a significant decrease in total cholesterol, LDL, and triglyceride after treatment. However, no significant difference was found in HDL levels and HOMA-IR. The supplementation of Indonesian shortfin eel by-product oil significantly improved lipid profile while effectively mitigating environmental challenges.

Exploring the Effects of Short-Term Daily Intake of Nitraria retusa Tea on Lipid Profile: A Pre-Post, Uncontrolled Pilot Study in Both Healthy and Overweight/Obese Adults.

In the present study, we aimed to explore the feasibility, compliance, and potential benefits of Nitraria retusa extract (NRE) intervention in both healthy (BMI ≤ 24.9 Kg/m2) and overweight/obese adults (BMI > 25 Kg/m2). A total of 98 participants, including 37 healthy individuals and 61 overweight/obese adults, were randomly assigned to either a low-dose (500 mg/day) or a high-dose (2000 mg/day) NRE intervention group. Plasma lipid biomarkers, liver and kidney functions, general hematology, and blood glucose levels were measured at the baseline and 10 days after intervention. While the lipid profile of the healthy participants did not show any statistically significant changes, the obese participants in the high-dose group experienced a significant decrease in triglyceride levels (within-group difference p value = 0.004) and an increase in HDL levels (within-group p value < 0.001). No significant differences were observed in other parameters, indicating that NRE at the given doses was safe. Furthermore, the study had impressive compliance and acceptability, with over 90% of participants completing the intervention and diligently following the study protocol. This pilot study represents the first investigation into the feasibility, acceptability, and potential benefits of NRE intervention on lipid profiles in human volunteers.

The Ketogenic Diet and Cardiovascular Diseases.

The most common and increasing causes of death worldwide are cardiovascular diseases (CVD). Taking into account the fact that diet is a key factor, it is worth exploring this aspect of CVD prevention and therapy. The aim of this article is to assess the potential of the ketogenic diet in the prevention and treatment of CVD. The article is a comprehensive, meticulous analysis of the literature in this area, taking into account the most recent studies currently available. The ketogenic diet has been shown to have a multifaceted effect on the prevention and treatment of CVD. Among other aspects, it has a beneficial effect on the blood lipid profile, even compared to other diets. It shows strong anti-inflammatory and cardioprotective potential, which is due, among other factors, to the anti-inflammatory properties of the state of ketosis, the elimination of simple sugars, the restriction of total carbohydrates and the supply of omega-3 fatty acids. In addition, ketone bodies provide "rescue fuel" for the diseased heart by affecting its metabolism. They also have a beneficial effect on the function of the vascular endothelium, including improving its function and inhibiting premature ageing. The ketogenic diet has a beneficial effect on blood pressure and other CVD risk factors through, among other aspects, weight loss. The evidence cited is often superior to that for standard diets, making it likely that the ketogenic diet shows advantages over other dietary models in the prevention and treatment of cardiovascular diseases. There is a legitimate need for further research in this area.

A Retrospective Evaluation of the Laboratory Findings of Dermatology Patients Whose Biotin Levels Were Checked.

Objective Biotin is widely known to be beneficial for the hair, nails, and skin, but there are only a few studies on biotin. We evaluated whether there is a relationship between biotin levels and age, gender, and frequently observed laboratory findings. We also evaluated biotin levels according to the reason for checking biotin levels. Methods One hundred five patients applied to the dermatology outpatient clinic and had their biotin levels checked. Patient files were retrospectively analyzed. Results There were a weak positive (r=0.207) relationship between biotin levels and basophil count, a weak positive (r=0.201) relationship between biotin levels and creatinine, and a weak positive (r=0.314) relationship between biotin levels and cholesterol/triglyceride ratio. There were a weak negative (r=-0.216) relationship between biotin levels and mean platelet volume (MPV) and a moderately negative (r=-0.315) relationship between biotin levels and triglyceride levels. Conclusion Biotin levels do not significantly differ with gender but increase with age. Although a weak correlation was detected between hemogram parameters and biotin levels with basophil percentage and mean platelet volume values, biotin did not significantly change hemogram parameters. The relationship between biotin levels and triglyceride levels was the most critical finding of our study. We recommend examining biotin levels in the patients with high triglyceride levels. When we encounter dermatological side effects related to the use of epidermal growth factor receptor tyrosine kinase inhibitors, we recommend evaluating biotin levels. We recommend that biotin supplementation be made only in the patients with deficiencies and that biotin levels be measured in the follow-up.

Novel application potential of cinaciguat in the treatment of mixed hyperlipidemia through targeting PTL/NPC1L1 and alleviating intestinal microbiota dysbiosis and metabolic disorders.

Mixed hyperlipidemia, characterized by high levels of triglycerides and cholesterol, is a key risk factor leading to atherosclerosis and other cardiovascular diseases. Existing clinical drugs usually only work on a single indicator, decreasing either triglyceride or cholesterol levels. Developing dual-acting agents that reduce both triglycerides and cholesterol remains a great challenge. Pancreatic triglyceride lipase (PTL) and Niemann-Pick C1-like 1 (NPC1L1) have been identified as crucial proteins in the transport of triglycerides and cholesterol. Here, cinaciguat, a known agent used in the treatment of acute decompensated heart failure, was identified as a potent dual inhibitor targeting PTL and NPC1L1. We presented in vitro evidence from surface plasmon resonance analysis that cinaciguat interacted with PTL and NPC1L1. Furthermore, cinaciguat exhibited potent PTL-inhibition activity. Fluorescence-labeled cholesterol uptake analysis and confocal imaging showed that cinaciguat effectively inhibited cholesterol uptake. In vivo evaluation showed that cinaciguat significantly reduced the plasma levels of triglycerides and cholesterol, and effectively alleviated high-fat diet-induced intestinal microbiota dysbiosis and metabolic disorders. These results collectively suggest that cinaciguat has the potential to be further developed for the therapy of mixed hyperlipidemia.

Pre-calving energy density and rumen protected lysine impacted blood metabolites and biomarkers of liver functions in dairy cows during the transition period.

Dairy cows usually face negative energy balance and disorders of normal organ function due to a mismatch between energy intake and energy demand. Negative energy balance directly affects liver function and blood metabolites because the liver is used as source of energy supply and a center of metabolic activity. This study was aimed to determine the effect of pre-calving energy density and rumen-protected lysine on blood metabolites and biomarkers of liver functions in the dairy cows during the transition period. Forty 3rd lactation Holstein cows going to enter their 4th lactation were randomly allocated to one of the four dietary treatments (high energy with rumen-protected lysine (HERPL) = 1.53NEL plus 40 g Lys, high energy without lysine (HECK) = 1.53NEL, low energy with rumen-protected lysine (LERPL) = 1.37NEL plus 40 g Lys, and low energy without lysine (LECK) = 1.37NEL arranged in a 2 × 2 factorial design. Blood samples were collected during the transition period, and concentrations of blood metabolites and biomarkers of liver function were measured. Interaction between pre-calving high-energy diet and rumen-protected lysine tended to increase plasma albumin, numerically increased glucose, decreased triglyceride, total bilirubin, and aspartate aminotransferase concentrations. The result revealed that pre-calving high-energy density increased insulin, albumin and decreased blood urea nitrogen and total bilirubin concentrations and substantial favor liver functions during the transition period.

Carnitine supplementation increases serum concentrations of free carnitine and total acylcarnitine in preterm neonates: A retrospective cohort study.

OBJECTIVE: Our goal was to determine the efficacy of the American Society for Parenteral and Enteral Nutrition's recommended carnitine dosage of 5 mg/kg/day in maintaining normal serum free carnitine and total acylcarnitine levels in preterm neonates receiving parenteral nutrition (PN). STUDY DESIGN: A retrospective cohort study was conducted on neonates born <30 weeks gestation and weighing <1250 g, comparing those who received carnitine supplementation to those without supplementation. Free carnitine and total acylcarnitine data were collected from routine newborn screens in the first days of life and on full enetral feeds. Univariate analysis was performed, and those factors that were significantly different between the two groups were adjusted for using mixed effects analysis. RESULTS: There were 108 supplemented and 45 unsupplemented neonates in the study. At baseline, free carnitine (19.8 ± 3.3 vs 18.9 ± 3.7 µmol/L, P = 0.53) and total acylcarnitine (26.6 ± 5.1 vs 22.5 ± 7.1 µmol/L, P = 0.11) were similar between the two groups. At full enteral feeds, compared with unsupplemented group, supplemented infants had significantly higher free carnitine (27.1 ± 16.4 vs 17.1 ± 8.5 µmol/L, P < 0.001) and total acylcarnitine (30.3 ± 11.5 vs 20.2 ± 10.1 µmol/L, P < 0.001). None of the supplemented neonates developed biochemical carnitine deficiency as compared with 18% in the unsupplemented group (P < 0.001). No difference was observed in time to reach full lipid provision, and there were no differences in the change in the triglyceride levels from baseline to the time on full PN lipid provision (P = 0.39). CONCLUSION: Preterm neonates routinely supplemented with parenteral carnitine at 5 mg/kg/day demonstrated higher free carnitine and total acylcarnitine levels at full feeds, with none developing biochemical carnitine deficiency.