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The therapeutic effect of reactive oxygen species (ROS)-involved cancer therapies is significantly limited by shortage of oxy-substrates, such as hypoxia in photodynamic therapy (PDT) and insufficient hydrogen peroxide (H 2 O 2 ) in chemodynamic therapy (CDT). Here, we report a H 2 O 2 /O 2 self-supplying nanoagent, (MSNs@CaO 2 -ICG)@LA, which consists of manganese silicate (MSN)-supported calcium peroxide (CaO 2 ) and indocyanine green (ICG) with further surface modification of phase-change material lauric acid (LA). Under laser irradiation, ICG simultaneously generates singlet oxygen and emits heat to melt the LA. The exposed CaO 2 reacts with water to produce O 2 and H 2 O 2 for hypoxia-relieved ICG-mediated PDT and H 2 O 2 -supplying MSN-based CDT, acting as an open source strategy for ROS production. Additionally, the MSNs-induced glutathione depletion protects ROS from scavenging, termed reduce expenditure. This open source and reduce expenditure strategy is effective in inhibiting tumor growth both in vitro and in vivo, and significantly improves ROS generation efficiency from multi-level for ROS-involved cancer therapies. The supply of oxygen species for dynamic therapy is a major limitation. Here, the authors report on a complex of calcium peroxide with photo/chemo dynamic agents, where NIR heating causes the release of calcium peroxide to generate oxygen and hydrogen peroxide for photodynamic and chemodynamic therapy.

Gut microbiota has been demonstrated to be involved in intestinal nutrition, defense, and immunity, as well as participating in disease progression. This study was to investigate gut microbiota changes in chickens challenged with netB-positive Clostridium perfringens strain (CP1) and/or the predisposing Eimeria species (Eimeria) and fed diets with fishmeal supplementation. In addition, the effects of lauric acid, a medium-chain fatty acid (MCFA), on necrotic enteritis (NE) reduction and modulation of microbiota were evaluated. The results demonstrated that microbial communities in the jejunum were distinct from those in the cecum, and the microbial community change was more significant in jejunum. Challenge of CP1 in conjunction with Eimeria significantly reduced species diversity in jejunal microbiota, but cecal microbiota remained stable. In the jejunum, CP1 challenge increased the abundance of the genera of Clostridium sensu stricto 1, Escherichia Shigella, and Weissella, but significantly decreased the population of Lactobacillus. Eimeria infection on its own was unable to promote NE, demonstrating decrements of Clostridium sensu stricto 1 and Lactobacillus. Co-infection with CP1 and Eimeria reproduced the majority of NE lesions with significant increment of Clostridium sensu stricto 1 and reduction in Lactobacillus. The advance of changes on these two taxa increased the severity of NE lesions. Further analyses of metagenomeSeq, STAMP, and LEfSe consistently showed significant overgrowth of Clostridium sensu stricto 1 was associated with NE. The supplementation of lauric acid did not reduce NE incidence and severity but decreased the relative abundance of Escherichia Shigella. In conclusion, significant overgrowth of C. perfringens as well as other Clostridium species in Clostridium sensu stricto 1 with the decrement of Lactobacillus in the jejunum is the featured microbiota correlated with NE. Controlling proliferation of Clostridium sensu stricto 1 and manipulation of Lactobacillus in the jejunum should be the strategy to prevent NE.

Lauric acid (LA) is a crucial medium-chain fatty acid (MCFA) that has many beneficial effects on humans and animals. This study aimed to investigate the effects of LA on the intestinal barrier, immune functions, serum metabolism, and gut microbiota of broilers under lipopolysaccharide (LPS) challenge. A total of 384 one-day-old broilers were randomly divided into four groups, and fed with a basal diet, or a basal diet supplemented with 75 mg/kg antibiotic (ANT), or a basal diet supplemented with 1000 mg/kg LA. After 42 days of feeding, three groups were intraperitoneally injected with 0.5 mg/kg Escherichia coli - derived LPS (LPS, ANT+LPS and LA+LPS groups) for three consecutive days, and the control (CON) group was injected with the same volume of saline. Then, the birds were sacrificed. Results showed that LA pretreatment significantly alleviated the weight loss and intestinal mucosal injuries caused by LPS challenge. LA enhanced immune functions and inhibited inflammatory responses by upregulating the concentrations of immunoglobulins (IgA, IgM, and IgY), decreasing IL-6 and increasing IL-4 and IL-10. Metabolomics analysis revealed a significant difference of serum metabolites by LA pretreatment. Twenty-seven serum metabolic biomarkers were identified and mostly belong to lipids. LA also markedly modulated the pathway for sphingolipid metabolism, suggesting its ability to regulate lipid metabolism. Moreover,16S rRNA analysis showed that LA inhibited LPS-induced gut dysbiosis by altering cecal microbial composition (reducing Escherichia-Shigella , Barnesiella and Alistipes , and increasing Lactobacillus and Bacteroides ), and modulating the production of volatile fatty acids (VFAs). Pearson’s correlation assays showed that alterations in serum metabolism and gut microbiota were strongly correlated to the immune factors; there were also strong correlations between serum metabolites and microbiota composition. The results highlight the potential of LA as a dietary supplement to combat bacterial LPS challenge in animal production and to promote food safety.

Virgin coconut oil is a useful substance in our daily life. It contains a high percentage of lauric acid which has many health benefits. The current industry has developed several methods to extract the oil out from the coconut fruit. This review paper aims to highlight several common extraction processes used in modern industries that includes cold extraction, hot extraction, low-pressure extraction, chilling, freezing and thawing method, fermentation, centrifugation, enzymatic extraction and supercritical fluid carbon dioxide. Different extraction methods will produce coconut oil with different yields and purities of lauric acid, thus having different uses and applications. Challenges that are faced by the industries in extracting the coconut oil using different methods of extraction are important to be explored so that advancement in the oil extraction technology can be done for efficient downstream processing. This study is vital as it provides insights that could enhance the production of coconut oil.

Cancer‐derived myocardial damage is an important cause of death in cancer patients. However, the development of dietary interventions for treating such damage has not been advanced. Here, we investigated the effect of dietary intervention with lauric acid (LAA) and glucose, which was effective against skeletal muscle sarcopenia in a mouse cachexia model, on myocardial damage. Treatment of H9c2 rat cardiomyoblasts with lauric acid promoted mitochondrial respiration and increased ATP production by Seahorse flux analysis, but did not increase oxidative stress. Glycolysis was also promoted by LAA. In contrast, mitochondrial respiration and ATP production were suppressed, and oxidative stress was increased in an in vitro cachexia model in which cardiomyoblasts were treated with mouse cachexia ascites. Ascites‐treated H9c2 cells with concurrent treatment with LAA and high glucose showed that mitochondrial respiration and glycolysis were promoted more than that of the control, and ATP was restored to the level of the control. Oxidative stress was also reduced by the combined treatment. In the mouse cachexia model, myocardiac atrophy and decreased levels of a marker of muscle maturity, SDS‐soluble MYL1, were observed. When LAA in CE‐2 diet was orally administered alone, no significant rescue was observed in the cancer‐derived myocardial disorder. In contrast, combined oral administration of LAA and glucose recovered myocardial atrophy and MYL1 to levels observed in the control without increase in the cancer weight. Therefore, it is suggested that dietary intervention using a combination of LAA and glucose for cancer cachexia might improve cancer‐derived myocardial damage. We elucidated that cancer‐derived myocardial damage results mainly from oxidative stress. The combined administration of LAA and glucose can effectively provide protective effects against myocardial damage and promote recovery.

The in ovo-injection technique was employed as an early-life nutritional strategy to improve the health and productivity of birds by delivering nutrients and bioactive compounds directly to the developing embryo. This study explored the innovative use of in ovo administration of nano-lauric acid (NLA) as a strategy for the metabolic programming of broiler chicks. The goal was to improve hatchability, stimulate hepatic antioxidant activity, regulate growth-related genes, and support intestinal development in newly hatched chicks. A total of 400 fertile eggs from a 40-week-old Arbor Acres breeder flock were randomly divided into four treatment groups: a non-injected control group (CN), a vehicle-injected control group (CP; 0.1 mL of sterile distilled water), and two NLA-treated groups receiving either 2.5 mg/egg (NLA 2.5) or 5 mg/egg (NLA 5) of NLA, each dissolved in 0.1 mL of sterile distilled water. Injections were administered into the yolk sac on day 12 of incubation. Post-hatching, the hatchability percentage was recorded. Serum lipid profiles, hepatic redox status, and the expression level of hepatic genes, nuclear factor erythroid 2–related factor 2 (NRF2), mitochondrial superoxide dismutase 2 (mt-SOD2), and insulin-like growth factors 1 and 2 (IGF-1 and IGF-2) were evaluated. Additionally, the intestinal morphology of the newly hatched chicks was examined. Hatchability % was significantly reduced in the NLA 5 group (80%) compared to the CN (98%), CP (97%), and NLA 2.5 (96%) groups. The findings showed that in ovo injection of NLA at 2.5 mg/egg was therefore identified as optimal, significantly improving lipid metabolism by reducing serum triglycerides, LDL, VLDL, and cholesterol, while increasing HDL cholesterol compared to controls ( P  < 0.05). Hepatic antioxidant defense was significantly improved through the decrease of malondialdehyde (MDA) and increase of reduced glutathione (GSH) concentrations ( P  < 0.05). This enhancement was associated with the upregulation of NRF-2 and mt-SOD2 by (4.04; 3.69-folds, respectively) and stimulation of anabolic signaling genes IGF-1 and IGF-2 by (4.08 and 2.3-folds; respectively) ( P  < 0.05). In addition, intestinal development has been significantly promoted via increased villus height and crypt depth ( P  < 0.05). Our findings demonstrate that  in ovo  NLA supplementation at 2.5 mg/egg effectively enhances lipid utilization, activates NRF2-mediated antioxidant pathways, and stimulates anabolic signaling. This targeted nutritional strategy proves to be a safe and effective method for pre-hatch metabolic programming, with significant potential to improve post-hatch health and performance in broilers.

Lauric acid (LA) has a broad spectrum of anti-microbiological activities against enveloped viruses and various bacteria, and might be useful to protect against microbial infection and control the balance and distribution of bacteria in human gut microbiota. It is not necessarily more difficult to measure antimicrobial activity the traditional way, but it is, however, more laborious. In the present study, we developed a new method to measure the antimicrobial activity of LA in multiple samples with a microplate reader. A “test complex” (TC) was produced consisting of 100 μL of agar medium with LA in the bottom layer and 300 μL of broth in the top layer in 96-well deep-well microplates. Afterward, analysis of the broth in the top layer showed that the antimicrobial activity was the same as that of the “control complex,” (CC) which consisted of 100 μL of agar medium in the bottom layer and 300 μL of broth with LA in the top layer. Furthermore, evaluation of the antimicrobial effect of the TC when using a microplate reader was the same as that with the use of the colony counting method. The colony counting method has confirmed that the antimicrobial activity of LA when bacteria are inoculated into the broth was equivalent between CC and TC, and we validated this by correlating the number of bacteria with absorbance. In addition, the broth itself in TC was transparent enough that the turbidity of broth can be used as an index of the number of bacteria, which enabled the use of a microplate reader for multiple samples. For human gut microbes, LA was shown to have low antimicrobial activity against commensal lactic acid bacteria, but high antimicrobial activity against pathogenic Bacteroides and Clostridium, suggesting that LA might modulate intestinal health, as confirmed by the proposed method.

Skeletal muscle volume is associated with prognosis of cancer patients. Maintenance of skeletal muscle is an essential concern in cancer treatment. In nutritional intervention, it is important to focus on differences in metabolism between tumor and skeletal muscle. We examined the influence of oral intake of glucose (0%, 10%, 50%) and 2% medium‐chain fatty acid (lauric acid, LAA, C12:0) on tumor growth and skeletal muscle atrophy in mouse peritoneal metastasis models using CT26 mouse colon cancer cells and HT29 human colon cancer cells. After 2 weeks of experimental breeding, skeletal muscle and tumor were removed and analyzed. Glucose intake contributed to prevention of skeletal muscle atrophy in a sugar concentration‐dependent way and also promoted tumor growth. LAA ingestion elevated the level of skeletal muscle protein and suppressed tumor growth by inducing tumor‐selective oxidative stress production. When a combination of glucose and LAA was ingested, skeletal muscle mass increased and tumor growth was suppressed. Our results confirmed that although glucose is an important nutrient for the prevention of skeletal muscle atrophy, it may also foster tumor growth. However, the ingestion of LAA inhibited tumor growth, and its combination with glucose promoted skeletal muscle integrity and function, without stimulating tumor growth. These findings suggest novel strategies for the prevention of skeletal muscle atrophy. Consistent with previous reports, although glucose supplementation alone may promote tumor development, in addition to preserving muscle integrity, the combination of glucose with medium‐chain fatty acids was found to exert muscle‐protecting effects while not affecting (or even suppressing) tumor growth.

Statins are widely prescribed for reducing LDL-cholesterol (C) and risk for cardiovascular disease (CVD), but there is considerable variation in therapeutic response. We used a gas chromatography-time-of-flight mass-spectrometry-based metabolomics platform to evaluate global effects of simvastatin on intermediary metabolism. Analyses were conducted in 148 participants in the Cholesterol and Pharmacogenetics study who were profiled pre and six weeks post treatment with 40 mg/day simvastatin: 100 randomly selected from the full range of the LDL-C response distribution and 24 each from the top and bottom 10% of this distribution (\"good\" and \"poor\" responders, respectively). The metabolic signature of drug exposure in the full range of responders included essential amino acids, lauric acid (p<0.0055, q<0.055), and alpha-tocopherol (p<0.0003, q<0.017). Using the HumanCyc database and pathway enrichment analysis, we observed that the metabolites of drug exposure were enriched for the pathway class amino acid degradation (p<0.0032). Metabolites whose change correlated with LDL-C lowering response to simvastatin in the full range responders included cystine, urea cycle intermediates, and the dibasic amino acids ornithine, citrulline and lysine. These dibasic amino acids share plasma membrane transporters with arginine, the rate-limiting substrate for nitric oxide synthase (NOS), a critical mediator of cardiovascular health. Baseline metabolic profiles of the good and poor responders were analyzed by orthogonal partial least square discriminant analysis so as to determine the metabolites that best separated the two response groups and could be predictive of LDL-C response. Among these were xanthine, 2-hydroxyvaleric acid, succinic acid, stearic acid, and fructose. Together, the findings from this study indicate that clusters of metabolites involved in multiple pathways not directly connected with cholesterol metabolism may play a role in modulating the response to simvastatin treatment. ClinicalTrials.gov NCT00451828.

Cytochrome P450 enzymes are responsible for the phase I metabolism of approximately 75% of known pharmaceuticals. P450s perform this and other important biological functions through the controlled activation of C-H bonds. Here, we report the spectroscopic and kinetic characterization of the long-sought principal intermediate involved in this process, P450 compound I (P450-I), which we prepared in approximately 75% yield by reacting ferric CYP119 with m-chloroperbenzoic acid. The Mössbauer spectrum of CYP119-I is similar to that of chloroperoxidase compound I, although its electron paramagnetic resonance spectrum reflects an increase in |J|/D, the ratio of the exchange coupling to the zero-field splitting. CYP119-I hydroxylates the unactivated C-H bonds of lauric acid [D(C-H) approximately 100 kilocalories per mole], with an apparent second-order rate constant of kapp = 1.1 x 10⁷ per molar per second at 4°C. Direct measurements put a lower limit of k ≥ 210 per second on the rate constant for bound substrate oxidation, whereas analyses involving kinetic isotope effects predict a value in excess of 1400 per second.