Production and evaluation of novel functional cream cottage cheese fortified with bovine colostrum and probiotic bacteria.

Nutrient-dense colostrum can be employed as a functional food ingredient. This work aimed to produce novel functional probiotic Cream cottage cheese (FPC) using probiotic (ABT) culture and bovine colostrum powder (BCP) at levels of 1, 2, and 3%. Physicochemical and functional properties (antioxidant activity, fatty acid profile, and antibacterial activity) were analyzed. The outcome revealed that hardness, cohesiveness, and gumminess were increased while springiness and chewiness were decreased for the treated cheeses. In FPC, medium-chain fatty acids were the predominant forms, followed by short- and long-chain fatty acids, polyunsaturated (PUFA), and small amounts of monounsaturated (MUFA). The antioxidant activity of all the cheese samples was significantly (P < 0.05) increased by increasing the quantity of colostrum powder and lengthening storage time. Color parameters were influenced by enrichment with BCP, whether in fresh or stored samples. With the addition of BCP, the growth of lactic acid bacteria and Bifidobacteria was enhanced, whereas that of pathogenic bacteria, mold and yeast, and coliform groups was inhibited. Cheeses fortified with 2% BCP had significantly higher score values than those in the other treatments. Therefore, it could be concluded that cottage cheese fortified with 2% BCP has high nutritional value and health benefits. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05910-0.

Pro-survival signaling regulates lipophagy essential for multiple myeloma resistance to stress-induced death.

Pro-survival metabolic adaptations to stress in tumorigenesis remain less well defined. We find that multiple myeloma (MM) is unexpectedly dependent on beta-oxidation of long-chain fatty acids (FAs) for survival under both basal and stress conditions. However, under stress conditions, a second pro-survival signal is required to sustain FA oxidation (FAO). We previously found that CD28 is expressed on MM cells and transduces a significant pro-survival/chemotherapy resistance signal. We now find that CD28 signaling regulates autophagy/lipophagy that involves activation of the Ca2+→AMPK→ULK1 axis and regulates the translation of ATG5 through HuR, resulting in sustained lipophagy, increased FAO, and enhanced MM survival. Conversely, blocking autophagy/lipophagy sensitizes MM to chemotherapy in vivo. Our findings link a pro-survival signal to FA availability needed to sustain the FAO required for cancer cell survival under stress conditions and identify lipophagy as a therapeutic target to overcome treatment resistance in MM.

Carbon dioxide sensitization delays the postharvest ripening and fatty acids composition of Capsicum fruit by regulating ethylene biosynthesis, malic acid and reactive oxygen species metabolism.

Present study would be significant in the sustenance of quality characters for postharvest storage of Capsicum fruit with CO2-sensitization in biocompatible manner. The present experiment describes effects of CO2 sensitization on delaying postharvest ripening through physiological attributes in Capsicum fruit. The experiment was conducted with acidified bicarbonate-derived CO2 exposure for 2 h on Capsicum fruit, kept under white light at 25 °C through 7 days postharvest storage. Initially, fruits responded well to CO2 as recorded sustenance of greenness and integrity of fruit coat resolved through scanning electron micrograph. Loss of water and accumulation of total soluble solids were marginally increased on CO2-sensitized fruit as compared to non-sensitized (control) fruit. The ethylene metabolism biosynthetic genes like CaACC synthase, CaACC oxidase were downregulated on CO2-sensitization. Accompanying ethylene metabolism cellular respiration was downregulated on CO2 induction as compared to control through 7 days of storage. Fruit coat photosynthesis decarboxylating reaction by NADP malic enzyme was upregulated to maintain the reduced carbon accumulation as recorded on 7 days of storage under the same condition. CO2-sensitization effectively reduced the lipid peroxides as oxidative stress products on ripening throughout the storage. Anti-oxidation reaction essentially downregulates the ROS-induced damages of biomolecules that otherwise are highly required for food preservation during postharvest storage. Thus, the major finding is that CO2-sensitization maintains a higher ratio of unsaturated to saturated fatty acids in fruit coat during storage. Tissue-specific downregulation of ROS also maintained the nuclear stability under CO2 exposure. These findings provide basic as well as applied insights for sustaining Capsicum fruit quality with CO2 exposure under postharvest storage. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-024-01471-4.

Oven-Roasting Effects the Fatty Acid Composition, Antioxidant Properties, and Oxidative Stability of Pomegranate (Punica granatum L.) Seed Oil.

In this study, we investigated the effect of roasting conditions and time on the physicochemical properties of pomegranate seed oil. We analyzed the fatty acid, total phenolic, flavonoid, tocopherol, and phytosterol contents of pomegranate seed oil extracted under four conditions: raw, heated at 160°C for 15 min, heated at 160°C for 20 min, and heated at 180°C for 10 min, which included three that were well-established to enhance nutritional and flavor properties. Furthermore, the oxidative stability was evaluated based on the acid value, peroxide value, and induction period. Roasting significantly decreased the contents of punicic acid, polyunsaturated fatty acids, tocopherol, and phytosterol and the 2,2-diphenyl-1-picrylhydrazyl radical scavenging capacity (P<0.05) of the oil. Conversely, saturated fatty acids, monounsaturated fatty acids, acid value, peroxide value, total phenolic and flavonoid contents, and induction period were significantly increased (P<0.05). Our results suggest that the roasting conditions were nutritionally and oxidatively stable, thereby enhancing the roasting process and providing a database for essential roasting treatments for pomegranate seed oil.

Fatty Acid Profile and Thermal Behavior of Fat-Rich Edible Insect Oils Compared to Commonly Consumed Animal and Plant Oils.

This study compared the physicochemical properties of edible insect oils from silkworm (Bombyx mori) pupa (SP), sago palm weevil (Rhynchophorus ferrugineus) larva (PW), and bamboo caterpillar (Omphisa fuscidentalis; BC) to oils from chicken skin (CK), beef back fat (BF), pork back fat (PF), salmon belly (SB), sea bass belly (BB), coconut (C), and peanut (P). The fatty acid profiles and thermal behaviors (crystallization and melting) of the extracted oils were evaluated. PW and BC oils had more saturated fatty acids (SFAs) than CK, PF, SB, BB, and P oils. SP oil had equivalent SFA content to CK and BB oils. Insect oils exhibited similar monounsaturated fatty acid concentrations in all samples, except C oils. PW and BC oils exhibited a higher content of palmitoleic acid than the other oils. SP oils contained polyunsaturated fatty acids similar to those in SB and BB oils, which were higher than those in PW, BC, CK, BF, and PF oils. SP oil also exhibited the highest concentration of α-linolenic acid (C18:3 n-3). Arachidonic acid (0.01-0.02 g/100 g) in all insect oils was lower level compared to CK, BF, PF, SB, and BB oils. SP oil (0.03 g/100 g) exhibited a slightly higher level of eicosapentaenoic acid compared to PW (0.01 g/100 g) and BC (0.01 g/100 g) oils. The insect oils were liquid at ambient temperature, solid below -15°C, and required less energy (△Hm-max) for melting than other samples. This study indicated that insects, particularly SP, could serve as an alternative source of fat to meet its growing demand.

Effects of gender and slaughter age on physicochemical and quality traits of Korean Hanwoo striploin.

Hanwoo beef is in high demand because of its unique flavor, freshness, and high-fat content. However, the longer rearing period required to enhance marbling in Hanwoo cattle has adverse environmental consequences, such as greenhouse gas emissions and overall rearing costs. To address consumer preferences for leaner and healthier meat, the Korean meat industry has recently introduced Hanwoo heifer meat as an alternative source, but its quality traits are still unclear. Nevertheless, there is a limited body of research exploring the impact of Hanwoo gender (steer, heifer, and cow) and their corresponding slaughter ages on meat quality traits. This study looked into how gender affected the physicochemical and qualitative features of Hanwoo striploin at their respective slaughter ages. Results revealed that cow striploin has higher levels of moisture (66.81%) and protein (20.76%), whereas it contains lower levels of fat (10.66%) and cholesterol (34.66 mg/100 g). Regarding the physicochemical properties, cow striploin exhibited significantly lower shear force, color indexes, and soluble collagen (p < 0.05). However, chondroitin (1.19%) and muscle fiber area (1,545.23 µm2) were significantly higher in steer striploin than in heifer and cow (p < 0.05). Cow striploin exhibited significantly higher levels of oleic acid, unsaturated fatty acids (UFAs), and monounsaturated fatty acids (MUFAs) while having lower levels of eicosadienoic acid and atherogenic index compared to the other two groups. Cows and heifers had higher concentrations of amino acid metabolites than striploin from steers. Furthermore, bioactive metabolites such as carnitine and carnosine content were found higher in cow and heifer respectively. Overall, Hanwoo cattle gender influences the qualitative attributes of striploin; nevertheless, compared to steer and heifer striploin, cow striploin is a relatively good source of protein, fatty acid content, and metabolites conducive to a healthy diet.

A reduction in dietary crude protein with amino acid balance has no negative effects in pigs.

The aim of this experiment was to evaluate the effects of low crude protein (CP) level with essential amino acids (AA) addition on growth performance, nutrient digestibility, microbiota, and volatile fatty acid composition in growing pigs. A total of 160 growing pigs (Landrace × Yorkshire × Duroc [LYD]; average initial body weight 16.68 ± 0.12 kg) were randomly allotted to one of the four treatments on the basis of initial body weight. A randomized complete block design was used to conduct this experiment in the Research Center of Animal Life Sciences at Kangwon National University. There were ten pigs/replicate with four replicates in each treatment. The treatments include; CON (Control, 17.2% dietary CP level), low protein (LP)-1.10 (15.7% dietary CP level + 1.10% lysine level), LP-1.15 (15.7% dietary CP level + 1.15% lysine level), LP1.2 (15.7% dietary CP level + 1.20% lysine level). The pigs fed CON and LP-1.2 diet showed greater final body weight than that of LP-1.1 diet (p < 0.05). Although average daily gain, average daily feed intake, and feed efficiency did not show any difference in phase 2 and 3, average daily gain and feed efficiency was significantly greater in CON and LP-1.20 in phase 1. However, the average daily feed intake did not show any difference during the experimental period. Isobutyric acid and isovaleric acid composition of LP treatments were lower than CON treatment in phase 2. Total branched chain fatty acid composition was significantly lower in LP treatment in phases 1 and 2. However, there was no significant difference among treatments in phase 3. The results of this study underscore the importance of AA supplementation when implementing a low-protein diet during the early growth phase (16-50 kg) in pigs.

Ectoine maintains the flavor and nutritional quality of broccoli during postharvest storage.

The bacterial derived osmolyte ectoine has been shown to stabilize cell structure and function, a property that may help to extend the shelf life of broccoli. The impact of ectoine on broccoli stored for 4 d at 20 °C and 90% relative humidity was investigated. Results indicated that 0.20% ectoine treatment maintained the quality of broccoli, by reducing rate of respiration and ethylene generation, while increasing the levels of total phenolics, flavonoids, TSS, soluble protein, and vitamin C, relative to control. Headspace-gas chromatography-mass spectrometry, transcriptomic and metabolomic analyses revealed that ectoine stabilized aroma components in broccoli by maintaining level of volatile compounds and altered the expression of genes and metabolites associated with sulfur metabolism, as well as fatty acid and amino acid biosynthesis pathways. These findings provide a greater insight into how ectoine preserves the flavor and nutritional quality of broccoli, thus, extending its shelf life.

Fatty acid preference for beta-oxidation in mitochondria of murine cultured astrocytes.

The brain utilizes glucose as a primary energy substrate but also fatty acids for the ß-oxidation in mitochondria. The ß-oxidation is reported to occur mainly in astrocytes, but its capacity and efficacy against different fatty acids remain unknown. Here, we show the fatty acid preference for the ß-oxidation in mitochondria of murine cultured astrocytes. Fatty acid oxidation assay using an extracellular flux analyzer showed that saturated or monosaturated fatty acids, palmitic acid and oleic acid, are preferred substrates over polyunsaturated fatty acids like arachidonic acid and docosahexaenoic acid. We also report that fatty acid binding proteins expressed in the astrocytes contribute less to fatty acid transport to mitochondria for ß-oxidation. Our results could give insight into understanding energy metabolism through fatty acid consumption in the brain.

USP19 Stabilizes TAK1 to Regulate High Glucose/Free Fatty Acid-induced Dysfunction in HK-2 Cells.

OBJECTIVE: Obesity-induced kidney injury contributes to the development of diabetic nephropathy (DN). Here, we identified the functions of ubiquitin-specific peptidase 19 (USP19) in HK-2 cells exposed to a combination of high glucose (HG) and free fatty acid (FFA) and determined its association with TGF-beta-activated kinase 1 (TAK1). METHODS: HK-2 cells were exposed to a combination of HG and FFA. USP19 mRNA expression was detected by quantitative RT-PCR (qRT-PCR), and protein analysis was performed by immunoblotting (IB). Cell growth was assessed by Cell Counting Kit-8 (CCK-8) viability and 5-ethynyl-2'-deoxyuridine (EdU) proliferation assays. Cell cycle distribution and apoptosis were detected by flow cytometry. The USP19/TAK1 interaction and ubiquitinated TAK1 levels were assayed by coimmunoprecipitation (Co-IP) assays and IB. RESULTS: In HG+FFA-challenged HK-2 cells, USP19 was highly expressed. USP19 knockdown attenuated HG+FFA-triggered growth inhibition and apoptosis promotion in HK-2 cells. Moreover, USP19 knockdown alleviated HG+FFA-mediated PTEN-induced putative kinase 1 (PINK1)/Parkin pathway inactivation and increased mitochondrial reactive oxygen species (ROS) generation in HK-2 cells. Mechanistically, USP19 stabilized the TAK1 protein through deubiquitination. Importantly, increased TAK1 expression reversed the USP19 knockdown-mediated phenotypic changes and PINK1/Parkin pathway activation in HG+FFA-challenged HK-2 cells. CONCLUSION: The findings revealed that USP19 plays a crucial role in promoting HK-2 cell dysfunction induced by combined stimulation with HG and FFAs by stabilizing TAK1, providing a potential therapeutic strategy for combating DN.

Lactate promotes fatty acid oxidation by the TCA cycle and mitochondrial respiration in muscles of obese mice.

Lower oxidative capacity in skeletal muscles (SKMs) is a prevailing cause of metabolic diseases. Exercise not only enhances the fatty acid oxidation (FAO) capacity of SKMs but also increases lactate levels. Given that lactate may contribute to tricarboxylic acid cycle (TCA) flux and impact monocarboxylate transporter 1 in the SKMs, we hypothesize that lactate can influence glucose and fatty acid (FA) metabolism. To test this hypothesis, we investigated the mechanism underlying lactate-driven FAO regulation in the SKM of mice with diet-induced obesity (DIO). Lactate was administered to DIO mice immediately after exercise over three weeks. We found that increased lactate levels enhanced energy expenditure mediated by fat metabolism during exercise recovery and decreased triglyceride levels in DIO mice SKMs. To determine the lactate-specific effects without exercise, we administered lactate to mice on a high-fat diet (HFD) for eight weeks. Similar to our exercise conditions, lactate increased FAO, TCA cycle activity, and mitochondrial respiration in the SKMs of HFD-fed mice. Additionally, under sufficient FA conditions, lactate increased uncoupling protein-3 abundance via the NADH/NAD+ shuttle. Conversely ATP synthase abundance decreased in the SKMs of HFD mice. Taken together, our results suggest that lactate amplifies the adaptive increase in FAO capacity mediated by the TCA cycle and mitochondrial respiration in SKMs under sufficient FA abundance.

Therapeutic implications of the metabolic changes associated with BRAF inhibition in melanoma.

Melanoma metabolism can be reprogrammed by activating BRAF mutations. These mutations are present in up to 50% of cutaneous melanomas, with the most common being V600E. BRAF mutations augment glycolysis to promote macromolecular synthesis and proliferation. Prior to the development of targeted anti-BRAF therapies, these mutations were associated with accelerated clinical disease in the metastatic setting. Combination BRAF and MEK inhibition is a first line treatment option for locally advanced or metastatic melanoma harboring targetable BRAF mutations. This therapy shows excellent response rates but these responses are not durable, with almost all patients developing resistance. When BRAF mutated melanoma cells are inhibited with targeted therapies the metabolism of those cells also changes. These cells rely less on glycolysis for energy production, and instead shift to a mitochondrial phenotype with upregulated TCA cycle activity and oxidative phosphorylation. An increased dependence on glutamine utilization is exhibited to support TCA cycle substrates in this metabolic rewiring of BRAF mutated melanoma. Herein we describe the relevant core metabolic pathways modulated by BRAF inhibition. These adaptive pathways represent vulnerabilities that could be targeted to overcome resistance to BRAF inhibitors. This review evaluates current and future therapeutic strategies that target metabolic reprogramming in melanoma cells, particularly in response to BRAF inhibition.

Microglial Piezo1 mechanosensitive channel as a therapeutic target in Alzheimer's disease.

Microglia are the resident macrophages of the central nervous system (CNS) that control brain development, maintain neural environments, respond to injuries, and regulate neuroinflammation. Despite their significant impact on various physiological and pathological processes across mammalian biology, there remains a notable gap in our understanding of how microglia perceive and transmit mechanical signals in both normal and diseased states. Recent studies have revealed that microglia possess the ability to detect changes in the mechanical properties of their environment, such as alterations in stiffness or pressure. These changes may occur during development, aging, or in pathological conditions such as trauma or neurodegenerative diseases. This review will discuss microglial Piezo1 mechanosensitive channels as potential therapeutic targets for Alzheimer's disease (AD). The structure, function, and modulation of Piezo1 will be discussed, as well as its role in facilitating microglial clearance of misfolded amyloid-ß (Aß) proteins implicated in the pathology of AD.

Nicotinamide mitigates visceral leishmaniasis by regulating inflammatory response and enhancing lipid metabolism.

BACKGROUND: Currently, treatment regimens for visceral leishmaniasis (VL) are limited because of the presence of numerous adverse effects. Nicotinamide, a readily available and cost-effective vitamin, has been widely acknowledged for its safety profile. Several studies have demonstrated the anti-leishmanial effects of nicotinamide in vitro. However, the potential role of nicotinamide in Leishmania infection in vivo remains elusive. METHODS: In this study, we assessed the efficacy of nicotinamide as a therapeutic intervention for VL caused by Leishmania infantum in an experimental mouse model and investigated its underlying molecular mechanisms. The potential molecular mechanism was explored through cytokine analysis, examination of spleen lymphocyte subsets, liver RNA-seq analysis, and pathway validation. RESULTS: Compared to the infection group, the group treated with nicotinamide demonstrated significant amelioration of hepatosplenomegaly and recovery from liver pathological damage. The NAM group exhibited parasite reduction rates of 79.7% in the liver and 86.7% in the spleen, respectively. Nicotinamide treatment significantly reduced the activation of excessive immune response in infected mice, thereby mitigating hepatosplenomegaly and injury. Furthermore, nicotinamide treatment enhanced fatty acid ß-oxidation by upregulating key enzymes to maintain lipid homeostasis. CONCLUSIONS: Our findings provide initial evidence supporting the safety and therapeutic efficacy of nicotinamide in the treatment of Leishmania infection in BALB/c mice, suggesting its potential as a viable drug for VL.

Comparative Efficacy of Omega-3 Fatty Acid with Other Interventions for Depression in Children and Adolescents: A Systematic Review and Network Meta-Analysis.

Background: The administration of omega-3 polyunsaturated fatty acid supplements is recommended as an adjuvant therapy for adults diagnosed with major depressive disorder. The evaluation of replicated data in combination treatment with omega-3 has been extensively conducted in adults over the past decade. However, the generalizability of these findings to pediatric groups is still uncertain. The objectives of this evaluation were twofold: (1) to evaluate the effectiveness of omega-3 and associated combination therapies in reducing the severity of depressive symptoms, and (2) to include remission rates (i.e., reduction of more than 50% in depression symptoms) as a measure of therapeutic efficacy. Methods: We conducted a literature search on PubMed/EMBASE from inception to October 2023. Data analyses were conducted using Stata (version 17.0). Results: We identified a total of 3168 articles. After eligibility screening of identified studies, nine studies (n = 561 participants) were included in our analysis herein. Pairwise comparisons revealed no significant improvement in depression symptoms for any intervention versus placebo. However, a clustered ranking plot identified omega-3 plus inositol as the most effective treatment for pediatric depression (77.3% efficacy). Omega-3 paired with psychoeducational psychotherapy significantly lowered the remission rate compared to placebo (standardized mean difference = 0.44, 95% confidence interval: 0.00-0.87, p = 0.048), resulting in a 91.5% remission rate, making it the most effective treatment in the study. Conclusions: Taken together, this network meta-analysis presents compelling evidence supporting the antidepressant effects of omega-3 in pediatric groups with depression. Future research should aim to investigate omega-3 as monotherapy for young individuals with depression, as well as investigate the efficacy of omega-3 in comparison to psychosocial interventions for affected individuals.

A comparative study of dietary amino acid patterns: unveiling growth, composition, and molecular signatures in juvenile Onychostoma macrolepis.

The wild Onychostoma macrolepis, a species under national class II protection in China, lacks a specific compound feed for captive rearing. Understanding the dietary amino acid pattern is crucial for optimal feed formulation. This study aimed to investigate the effects of the four different dietary amino acid patterns, i.e., anchovy fishmeal protein (FMP, control group) and muscle protein (MP), whole-body protein (WBP), fish egg protein (FEP) of juvenile Onychostoma macrolepis, on the growth performance, body composition, intestinal morphology, enzyme activities, and the expression levels of gh, igf, mtor genes in juveniles. In a 12-week feeding trial with 240 juveniles (3.46±0.04g), the MP group demonstrated superior outcomes in growth performance (FBW, WGR, SGR), feed utilization efficiency (PER, PRE, FCR). Notably, it exhibited higher crude protein content in whole-body fish, enhanced amino acid composition in the liver, and favorable fatty acid health indices (AI, TI, h/H) in muscle compared to other groups (P < 0.05). Morphologically, the MP and FMP groups exhibited healthy features. Additionally, the MP group displayed significantly higher activities of TPS, ALP, and SOD, along with elevated expression levels of gh, igf, mtor genes, distinguishing it from the other groups (P < 0.05). This study illustrated that the amino acid pattern of MP emerged as a suitable dietary amino acid pattern for juvenile Onychostoma macrolepis. Furthermore, the findings provide valuable insights for formulating effective feeds in conserving and sustainably farming protected species, enhancing the research's broader ecological and aquacultural significance.

The prognostic significance of pro-BNP and heart failure in acute pulmonary embolism: A systematic review.

Pulmonary embolism (PE) is the third most common type of cardiovascular disease and carries a high mortality rate of 30% if left untreated. Although it is commonly known that individuals who suffer heart failure (HF) are more likely to experience a pulmonary embolism, little is known concerning the prognostic relationship between acute PE and HF. This study aims to evaluate the prognostic usefulness of heart failure and pro-BNP in pulmonary embolism cases. A scientific literature search, including PubMed, Medline, and Cochrane reviews, was used to assess and evaluate the most pertinent research that has been published. The findings showed that increased N-terminal brain natriuretic peptide (NT-proBNP) levels could potentially identify pulmonary embolism patients with worse immediate prognoses and were highly predictive of all-cause death. Important prognostic information can be obtained from NT-proBNP and Heart-type Fatty Acid Binding Proteins (H-FABP) when examining individuals with PE. The heart, distal tubular cells of the renal system, and skeletal muscle are where H-FABP is primarily found, with myocardial cells having the highest concentration. Recent studies have indicated that these biomarkers may also help assess the severity of PE and its long-term risk.

Structural basis of the dehydratase module (hDH) of human fatty acid synthase.

The human fatty acid synthase (hFASN) produces fatty acids for cellar membrane construction, energy storage, biomolecule modifications and signal transduction. Abnormal expression and functions of hFASN highly associate with numerous human diseases such as obesity, diabetes, and cancers, and thereby it has been considered as a valuable potential drug target. So far, the structural and catalytic mechanisms of most of the hFASN enzymatic modules have been extensively studied, except the key dehydratase module (hDH). Here we presented the enzymatic characterization and the high-resolution crystal structure of hDH. We demonstrated that the hDH preferentially catalyzes the acyl substrates with short lengths between 4 to 8-carbons, and exhibits much lower enzymatic activity on longer substrates. Subsequent structural study showed that hDH displays a pseudo-dimeric organization with a single L-shaped composite hydrophobic catalytic tunnel as well as an atypical ACP binding site nearby, indicating that hDH achieves distinct substrate recognition and dehydration mechanisms compared to the conventional bacterial fatty acid dehydratases identified. Our findings laid the foundation for understanding the biological and pathogenic functions of hFASN, and may facilitate therapeutical drug development against diseases with abnormal functionality of hFASN.

Revealing the effect of sea buckthorn oil, fish oil and structured lipid on intestinal microbiota, colonic short chain fatty acid composition and serum lipid profiles in vivo.

In this study, the effects of sea buckthorn oil (SBO), fish oil (FO) and an enzymatically synthesized structured lipid (SL) on serum, short-chain fatty acids (SCFAs) and intestinal microbiota in Sprague-Dawley (SD) rats were investigated. The results demonstrated that FO, SBO, and SL effectively reduced the levels of high-density lipoprotein cholesterol and low-density lipoprotein cholesterol in the serum of SD rats. SBO increased serum triglyceride levels, while FO elevated total cholesterol levels. Furthermore, all three dietary lipids decreased short-chain fatty acid production and enhanced intestinal microbiota diversity. FO increased the abundance of intestinal microbiota including Romboutsia, Lactobacillus, Escherichia-Shigella, and Lachnospiraceae_NK4A136_group. Conversely, all three dietary lipids reduced the abundance of Klebsiella and Blautia. These findings provide a foundation for understanding the functionality of SBO and FO as well as their potential application in synthesizing novel SLs to regulate intestinal microbiota.

An optimal combination of four active components in Huangqin decoction for the synergistic sensitization of irinotecan against colorectal cancer.

BACKGROUND: Irinotecan (CPT-11) is a first-line treatment for advanced colorectal cancer (CRC). Four components (baicalin, baicalein, wogonin, and glycyrrhizic acid) derived from Huangqin Decoction (HQD) have been proven to enhance the anticancer activity of CPT-11 in our previous study. OBJECTIVE: This study aimed to determine the optimal combination of the four components for sensitizing CPT-11 as well as to explore the underlying mechanism. METHODS: The orthogonal design method was applied to obtain candidate combinations (Cmb1-9) of the four components. The influence of different combinations on the anticancer effect of CPT-11 was first evaluated in vitro by cell viability, wound healing ability, cloning formation, apoptosis, and cell cycle arrest. Then, a CRC xenograft mice model was constructed to evaluate the anticancer effect of the optimal combination in vivo. Potential mechanisms of the optimal combination exerting a sensitization effect combined with CPT-11 against CRC were analyzed by targeted metabolomics. RESULTS: In vitro experiments determined that Cmb8 comprised of baicalin, baicalein, wogonin, and glycyrrhizic acid at the concentrations of 17 µM, 47 µM, 46.5 µM and 9.8 µM respectively was the most effective combination. Importantly, the cell viability assay showed that Cmb8 exhibited synergistic anticancer activity in combination with CPT-11. In in vivo experiments, this combination (15 mg/kg of baicalin, 24 mg/kg of baicalein, 24 mg/kg of wogonin, and 15 mg/kg of glycyrrhizic acid) also showed a synergistic anticancer effect. Meanwhile, inflammatory factors and pathological examination of the colon showed that Cmb8 could alleviate the gastrointestinal damage induced by CPT-11. Metabolic profiling of the tumors suggested that the synergistic anticancer effect of Cmb8 might be related to the regulation of fatty acid metabolism. CONCLUSION: The optimal combination of four components derived from HQD for the synergistic sensitization of CPT-11 against CRC was identified.