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Haematitum is a commonly used mineral medicine. It is toxic, as recorded in the second volume of Chinese Materia Medica. Therefore, it should not be taken for a long time. In this study, the effects of Haematitum and calcined Haematitum on multiple organ injuries in mice were investigated, and the mechanism of the toxicity of the related organs was explored by metabolomics. The mice were randomly divided into the control group, Haematitum low-dose group(ZS-L group), Haematitum high-dose group(ZS-H group), and calcined Haematitum high-dose group(DZS-H group), with 12 mice in each group. Haematitum decoction was given by continuous intragastric administration for 10 days. Then the life situation was observed, and samples were taken to detect various indicators. The results showed that the ZS-H group showed obvious toxicity, with different degrees of toxicity damage in the intestinal tract,liver, spleen, and lung. ZS-L group had no toxic reaction. The toxicity of the DZS-H group was significantly reduced, and only the lung was damaged. Metabolomics technology was used to detect the lung tissue of mice in the control group and the ZS-H group, and a total of 15 kinds of significant difference metabolites were detected, mainly involved in choline metabolism in cancer, sphingolipid metabolism, and glycerophospholipid metabolism. Immunohistochemical results showed that the INSIG1 protein expression level in the lung tissue of mice in the ZS-H group was significantly higher than that in the control group. In summary, large doses and long-time use of Haematitum decoction will cause a variety of organ damage, and the same dose of calcined Haematitum is less toxic than Haematitum. In addition, a low dose of Haematitum has no obvious toxic effect. The dysfunction of lipid metabolic pathways such as sphingolipid and glycerophospholipid metabolism may be an important factor in Haematitum-induced pulmonary toxicity. This study provides a reference for further research on the mechanism of Haematitum pulmonary toxicity.
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Medicamentos Herbarios Chinos , Pulmón , Animales , Ratones , Medicamentos Herbarios Chinos/administración & dosificación , Masculino , Pulmón/efectos de los fármacos , Pulmón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Bazo/efectos de los fármacos , Bazo/metabolismo , Insuficiencia Multiorgánica/metabolismo , Insuficiencia Multiorgánica/etiología , Insuficiencia Multiorgánica/inducido químicamente , Femenino , Metabolómica , HumanosRESUMEN
The swift advancement of the solid oxide fuel cell (SOFC) sector necessitates a harmony between electrode performance and commercialization cost. The economic value of elements is frequently linked to their abundance in the Earth's crust. Here, we develop abundant rare-earth iron perovskite electrodes of Ln0.6Sr0.4FeO3-δ (Ln = La, Pr, and Nd) with high abundant rare-earth metals and preferred iron metal for SOFCs. All three symmetric electrode materials display a cubic perovskite phase and excellent chemical compatibility with Gd0.2Ce0.8O2-δ electrolyte. All three electrodes possess exceptional surface oxygen exchange ability. At 800°C, single cells with La0.6Sr0.4FeO3-δ, Pr0.6Sr0.4FeO3-δ, and Nd0.6Sr0.4FeO3-δ symmetric electrodes attained excellent open circuit voltages of 1.108, 1.101, and 1.097 V, respectively, as well as peak powers of 213.52, 281.12, and 254.58 mW cm-2. The results suggest that overall performance of abundant rare-earth iron perovskite electrodes has a favorable impact on the extensive expansion of SOFCs, presenting significant potential for practical applications.
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The high recurrence rate of cervical cancer is a leading cause of cancer deaths in women. 5-Fluorouracil (5-FU) is an antitumor drug used to treat many types of cancer, but its diminishing effectiveness and side effects limit its use. Norcantharidin (NCTD), a demethylated derivative of cantharidin, exhibits various biological activities. Here, we investigated whether NCTD could potentiate 5-FU to induce cervical cancer cell death. To assess the cell viability and synergistic effects of the drugs, cell counting kit-8 and colony formation assays were performed using HR-HPV-positive cervical cancer cell lines. Annexin V-FITC/PI staining and TUNEL assays were performed to confirm the induction of apoptosis. The synergistic effect of NCTD on the antitumor activity of 5-FU was analyzed using network pharmacology, molecular docking, and molecular dynamics simulations. Apoptosis-related proteins were examined using immunoblotting. The combination of NCTD and 5-FU was synergistic in cervical cancer cell lines. Network pharmacological analysis identified 10 common targets of NCTD and 5-FU for cervical cancer treatment. Molecular docking showed the strong binding affinity of both compounds with CA12, CASP9, and PTGS1. Molecular dynamics simulations showed that the complex system of both drugs with caspase-9 could be in a stable state. NCTD enhanced 5-FU-mediated cytotoxicity by activating apoptosis-related proteins. NCTD acts synergistically with 5-FU to inhibit cervical cancer cell proliferation. NCTD enhances 5-FU-induced apoptosis in cervical cancer cell lines via the caspase-dependent pathway.
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Fe-based Prussian blue (Fe-PB) analogues have emerged as promising cathode materials for sodium-ion batteries, owing to their cost-effectiveness, high theoretical capacity, and environmental friendliness. However, their practical application is hindered by [Fe(CN)6] defects, negatively impacting capacity and cycle stability. This work reports a hollow layered Fe-PB composite material using 1,3,5-benzenetricarboxylic acid (BTA) as a chelating and etching agent by the hydrothermal method. Compared to benzoic acid, our approach significantly reduces defects and enhances the yield of Fe-PB. Notably, the hollow layered structure shortens the diffusion path of sodium ions, enhances the activity of low-spin Fe in the Fe-PB lattice, and mitigates volume changes during Na-ion insertion/extraction into/from Fe-PB. As a sodium-ion battery cathode, this hollow layered Fe-PB exhibits an impressive initial capacity of 95.9 mAh g-1 at a high current density of 1 A g-1. Even after 500 cycles, it still maintains a considerable discharge capacity of 73.1 mAh g-1, showing a significantly lower capacity decay rate (0.048%) compared to the control sample (0.089%). Moreover, the full cell with BTA-PB-1.6 as the cathode and HC as the anode provides a considerable energy density of 312.2 Wh kg-1 at a power density of 291.0 W kg-1. This research not only enhances the Na storage performance of Fe-PB but also increases the yield of products obtained by hydrothermal methods, providing some technical reference for the production of PB materials using the low-yield hydrothermal method.
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Patients with ulcerative colitis (UC) have higher rates of depression. However, the mechanism of depression development remains unclear. The improvements of EPA and DHA on dextran sulfate sodium (DSS)-induced UC have been verified. Therefore, the present study mainly focused on the effects of EPA and DHA on UC-induced depression in C57BL/6 mice and the possible mechanisms involved. A forced swimming test and tail suspension experiment showed that EPA and DHA significantly improved DSS-induced depressive-like behavior. Further analysis demonstrated that EPA and DHA could significantly suppress the inflammation response of the gut and brain by regulating the NLRP3/ASC signal pathway. Moreover, intestine and brain barriers were maintained by enhancing ZO-1 and occludin expression. In addition, EPA and DHA also increased the serotonin (5-HT) concentration and synaptic proteins. Interestingly, EPA and DHA treatments increased the proportion of dominant bacteria, alpha diversity, and beta diversity. In conclusion, oral administration of EPA and DHA alleviated UC-induced depressive-like behavior in mice by modulating the inflammation, maintaining the mucosal and brain barriers, suppressing neuronal damage and reverting microbiota changes.
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Colitis Ulcerosa , Humanos , Ratones , Animales , Sulfato de Dextran/toxicidad , Ratones Endogámicos C57BL , Colitis Ulcerosa/metabolismo , Transducción de Señal , Inflamación/metabolismo , Modelos Animales de Enfermedad , Colon/metabolismoRESUMEN
This article concentrates on proposing a scalable deep reinforcement learning (DRL) method for a multiple unmanned surface vehicle (multi-USV) system to operate cooperative target invasion. The multi-USV system, which is made up of multiple invaders, needs to invade target areas in a specified time. A novel scalable reinforcement learning (RL) method called Scalable-MADDPG is proposed for the first time. In this method, the scale of the multi-USV system can be changed at any time without interrupting the training process. Then, to mitigate the policy oscillation after applying Scalable-MADDPG, a bi-directional long-short-term memory (Bi-LSTM) network is constructed. Moreover, an improved ϵ -greedy strategy is proposed to help balance the exploration and exploitation in RL. Furthermore, to enhance the robustness of the optimal policy, Ornstein-Uhlenbeck (OU) noise is added in this improved ϵ -greedy strategy during the training process. Finally, the scalable RL method is used to help the multi-USV system perform cooperative target invasion under complex marine environments. The effectiveness of Scalable-MADDPG is demonstrated through three experiments.
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Nerve damage caused by accumulated oxidative stress is one of the characteristics and main mechanisms of Alzheimer's disease (AD). Previous studies have shown that phosphatidylserine (PS) rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) plays a significant role in preventing and mitigating the progression of AD. However, whether DHA-PS and EPA-PS can directly protect primary hippocampal neurons against oxidative damage has not been studied. Here, the neuroprotective functions of DHA-PS and EPA-PS against H2O2/t-BHP-induced oxidative damage and the possible mechanisms were evaluated in primary hippocampal neurons. It was found that DHA-PS and EPA-PS could significantly improve cell morphology and promote the restoration of neural network structure. Further studies showed that both of them significantly alleviated oxidative stress-mediated mitochondrial dysfunction. EPA-PS significantly inhibited the phosphorylation of ERK, thus playing an anti-apoptotic role, and EPA-PS significantly increased the protein expressions of p-TrkB and p-CREB, thus playing a neuroprotective role. In addition, EPA-PS, rather than DHA-PS could enhance synaptic plasticity by increasing the expression of SYN, and both could significantly reduce the expression levels of p-GSK3ß and p-Tau. These results provide a scientific basis for the use of DHA/EPA-enriched phospholipids in the treatment of neurodegenerative diseases, and also provide a reference for the development of related functional foods.
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Enfermedad de Alzheimer , Fármacos Neuroprotectores , Humanos , Ácido Eicosapentaenoico/farmacología , Ácido Eicosapentaenoico/metabolismo , Ácidos Docosahexaenoicos/farmacología , Ácidos Docosahexaenoicos/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/metabolismo , Fosfatidilserinas/farmacología , Fosfatidilserinas/química , Peróxido de Hidrógeno/toxicidad , Peróxido de Hidrógeno/metabolismo , Estrés Oxidativo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Neuronas , HipocampoRESUMEN
Alzheimer's disease (AD) is a common neurodegenerative disease in the elderly. Dysregulation of intracellular Ca2+ homeostasis plays a critical role in the pathological development of AD. Dauricine (DAU) is a bisbenzylisoquinoline alkaloid isolated from Menispermum dauricum DC., which can prevent the influx of extracellular Ca2+ and inhibit the release of Ca2+ from the endoplasmic reticulum. DAU has a potential for anti-AD. However, it is unclear whether DAU can exert its anti-AD effect in vivo by regulating the Ca2+ related signaling pathways. Here, we investigated the effect and mechanism of DAU on D-galactose and AlCl3 combined-induced AD mice based on the Ca2+/CaM pathway. The results showed that DAU (1â¯mg/kg and 10â¯mg/kg for 30â¯days) treatment attenuated learning and memory deficits and improved the nesting ability of AD mice. The HE staining assay showed that DAU could inhibit the histopathological alterations and attenuate neuronal damage in the hippocampus and cortex of AD mice. Studies on the mechanism indicated that DAU decreased the phosphorylation of CaMKII and Tau and reduced the formation of NFTs in the hippocampus and cortex. DAU treatment also reduced the abnormally high expression of APP, BACE1, and Aß1-42, which inhibited the deposition of Aß plaques. Moreover, DAU could decrease Ca2+ levels and inhibit elevated CaM protein expression in the hippocampus and cortex of AD mice. The molecular docking results showed that DAU may have a high affinity with CaM or BACE1. DAU has a beneficial impact on pathological changes in AD mice induced by D-galactose and AlCl3 and may act by negative regulation of the Ca2+/CaM pathway and its downstream molecules such as CaMKII and BACE1.
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Enfermedad de Alzheimer , Bencilisoquinolinas , Disfunción Cognitiva , Enfermedades Neurodegenerativas , Ratones , Animales , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/metabolismo , Galactosa/toxicidad , Galactosa/metabolismo , Secretasas de la Proteína Precursora del Amiloide/efectos adversos , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Simulación del Acoplamiento Molecular , Ácido Aspártico Endopeptidasas/efectos adversos , Ácido Aspártico Endopeptidasas/metabolismo , Bencilisoquinolinas/efectos adversos , Hipocampo , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/tratamiento farmacológico , Modelos Animales de Enfermedad , Péptidos beta-Amiloides/metabolismo , Ratones TransgénicosRESUMEN
The growth and development of the fetus and newborn throughout pregnancy and lactation are directly related to the nutritional status of the mother, which has a significant impact on the health of the offspring. The purpose of this experiment was to investigate the susceptibility of n-3 polyunsaturated fatty acid deficiency in early life to seizures in adulthood. The n-3 PUFAs-deficient mice's offspring were established and then fed with α-LNA diet, DHA-enriched ethyl ester, and DHA-enriched phospholipid-containing diets for 17 days at the age of eight weeks. During this period, animals received intraperitoneal injections of 35 mg/kg of pentylenetetrazol (PTZ) every other day for eight days. The results showed that dietary n-3 PUFA-deficiency in early life could aggravate PTZ-induced epileptic seizures and brain disorders. Notably, nutritional supplementation with n-3 PUFAs in adulthood for 17 days could significantly recover the brain n-3 fatty acid and alleviate the epilepsy susceptibility as well as raise seizure threshold to different levels by mediating the neurotransmitter disturbance and mitochondria-dependent apoptosis, demyelination, and neuroinflammation status of the hippocampus. DHA-enriched phospholipid possessed a superior effect on alleviating the seizure compared to α-LNA and DHA-enriched ethyl ester. Dietary n-3 PUFA deficiency in early life increases the susceptibility to PTZ-induced epilepsy in adult offspring, and nutritional supplementation with n-3 PUFAs enhances the tolerance to the epileptic seizure.
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Epilepsia , Ácidos Grasos Omega-3 , Femenino , Embarazo , Ratones , Animales , Pentilenotetrazol/toxicidad , Ácidos Docosahexaenoicos , Ácidos Grasos Omega-3/farmacología , Dieta , Fosfolípidos , Suplementos Dietéticos , Epilepsia/inducido químicamente , Epilepsia/tratamiento farmacológico , Convulsiones/inducido químicamente , Convulsiones/tratamiento farmacológico , Convulsiones/prevención & controlRESUMEN
Inverse lithography technology (ILT), such as source mask optimization (SMO), is used to improve lithography performance. Usually, a single objective cost function is selected in ILT, and an optimal structure for one field point is achieved. The optimal structure is not the case for other images at full field points where the aberrations of the lithography system are different, even in high-quality lithography tools. The optimal structure that must match the high-performance images at the full field is urgently required for extreme ultraviolet lithography (EUVL). In contrast, multi-objective optimization algorithms (MOAs) limit the application of multi-objective ILT. Assigning target priority is incomplete in current MOAs, which results in the over-optimization of some targets and under-optimization of others. In this study, multi-objective ILT and a hybrid dynamic priority (HDP) algorithm were investigated and developed. High-performance images with high fidelity and high uniformity were obtained at multi-field and multi-clip areas across the die. A hybrid criterion was developed for the completion and reasonable prioritization of each target to ensure sufficient improvement. Compared to the current MOAs, the uniformity of images at full-field points was improved by up to 31.1% by the HDP algorithm in the case of multi-field wavefront error-aware SMO. The multi-clip source optimization (SO) problem showed the universality of the HDP algorithm to deal with different ILT problems. It acquired higher imaging uniformity than existing MOAs, which indicated that the HDP is more qualified for multi-objective ILT optimization than existing MOAs.
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A novel catalyst obtained from the pyrolysis of a Co/Fe/Zn zeolitic imidazolite framework was prepared as an oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) electrocatalyst. The Co-N-C-900 catalyst displays promising ORR and OER activity with E1/2 = 0.854 V and Ej=10 = 1.780 V. The rechargeable Zn-air battery equipped with a Co-N-C-900 cathode electrocatalyst illustrates a high peak power density of 275 mW cm-2, which is much superior than that of commercial 20% Pt/C. Significantly, the designed Zn-air battery with the Co-N-C-900 catalyst presents good cycling stability for 180 h in the rechargeable Zn-air battery.
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OBJECTIVE: To observe the effect of electroacupuncture (EA) pretreatment at "Quchi "(LI11) and "Xuehai "(SP10) on expression of interleukin (IL)-33, suppression of tumorigenicity 2 (ST2) and mast cell degranulation in sensitive area of skin tissue in rats with urticaria, so as to explore its mechanisms underlying prevention of urticaria. METHODS: A total of 32 male SD rats were randomly divided into blank control, model, EA preconditioning and medication groups, with 8 rats in each group. The urticaria model was established by topical injection of the prepared anti-ovalbumin serum (foreign serum, 0.1 mL/spot) along the bilateral sides of the spinal column on the back, followed by injection of mixture solution of ovalbumin, 0.5% evans blue and normal saline via the tail vein 48 h later. EA intervention (2 Hz/15 Hz, 1 mA) was applied to bilateral LI11 and SP10 for 20 min, once daily for 7 d before modeling.Back sensitization was started from the 5th day on. Rats of the medication group received gavage of loratadine, and those of the model group received gavage of the same volume of normal saline. The diameter of evans blue spots at the back skin tissue was measured; the histopathological changes of the blue spot tissues were observed by light microscope after H.E. staining. The state of degranulation of mast cells in the subcutaneous loose connective tissue was observed by using toluidine blue staining. Serum IgE and histamine contents were detected by ELISA, and the immunoactivity of IL-33 and ST2 in the skin and subcutaneous tissues of the sensitized spots (evans blue exudation spots) was observed by immunohistochemistry. RESULTS: Compared with the blank control group, the diameter of evans blue spot, degranulation rate of mast cells, serum IgE and histamine contents, and the immunoactivity of IL-33 and ST2 in the evans blue exudation spot tissues were significantly increased in the model group (P<0.01). In comparison with the model group, the increase of the above-mentioned indexes was reversed in both EA and medication groups (P<0.01ï¼P<0.05). No significant differences were found between the EA and medication groups in down-regulating the levels of the 6 indexes. H.E. staining of the blue spot tissues of rats in the model group showed incomplete structure of the epidermal layer of the skin, unclear interface of tissues, incomplete keratinization, chaotic epidermal cells, disorderly arrangement of fibers in the dermis, and infiltration of inflammatory cells and edema, which was relatively milder in the EA and medication groups. CONCLUSION: EA preconditioning can prevent urticaria (reduce size and sensitive reactions) in rats, which may be associated with its functions in lowering the level of IgE through inhibiting IL-33 and ST2.
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Terapia por Acupuntura , Electroacupuntura , Urticaria , Ratas , Masculino , Animales , Ratas Sprague-Dawley , Mastocitos , Proteína 1 Similar al Receptor de Interleucina-1 , Histamina , Azul de Evans , Interleucina-33/genética , Solución Salina , Urticaria/genética , Urticaria/terapia , Inmunoglobulina E , Puntos de Acupuntura , Receptores de Interleucina-1RESUMEN
Homeostasis of reactive oxygen species is required to maintain sperm maturation and capacitation. Docosahexaenoic acid (DHA) is accumulated in testicles and spermatozoa and has the ability to manipulate the redox status. The effects of dietary n-3 polyunsaturated fatty acid (n-3 PUFA) deficiency from early life to adulthood on the physiological and functional properties of males under the redox imbalance of testicular tissue deserve attention. The consecutive injection of hydrogen peroxide (H2O2) and tert-butyl hydroperoxide (t-BHP) for 15 days to induce oxidative stress in testicular tissue was used to elucidate the consequences of testicular n-3 PUFA deficiency. The results indicated that reactive oxygen species treatment in adult male mice with DHA deficiency in the testis could reduce spermatogenesis and disrupt sex hormone production, as well as trigger testicular lipid peroxidation and tissue damage. N-3 PUFA deficiency from early life to adulthood resulted in higher susceptibility to testicular dysfunction in the germinal function of supplying germ cells and the endocrine role of secreting hormones through the mechanism of aggravating mitochondria-mediated apoptosis and destruction of blood testicular barrier under oxidative stress, which might provide a basis for humans to reduce susceptibility to chronic disease and maintain reproductive health in adulthood through dietary interventions of n-3 PUFAs.
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Ácidos Grasos Omega-3 , Humanos , Ratones , Masculino , Animales , Especies Reactivas de Oxígeno , Peróxido de Hidrógeno/farmacología , Semen , Testículo , Ácidos Docosahexaenoicos/farmacologíaRESUMEN
Blood-brain barrier (BBB) impairment is related to the development of Alzheimer's disease (AD), which is dependent not only on tight junction but also on transcytosis of brain endothelial cells (BECs) in the BBB. Aging induces the decrease of ligand-specific receptor-mediated transcytosis (RMT) and the increase of non-specific caveolar transcytosis in BECs, which lead to the entry into parenchyma of neurotoxic proteins and the smaller therapeutic index in central nervous system drug delivery, further provoking neurodegenerative disease. A previous study suggests that sea-derived Antarctic krill oil (AKO) exhibits synergistic effects with land-derived nobiletin (NOB) and theanine (THE) on ameliorating memory and cognitive deficiency in SAMP8 mice. However, it is still unclear whether BBB change is involved. Hence, the effects of AKO combined with NOB and THE on aging-induced BBB impairment, including tight junction between BECs, ligand-specific RMT, and non-specific caveolar transcytosis in BECs, are investigated. The results suggest that AKO exhibits synergistic effects with NOB and THE on regulating ligand-specific RMT in BBB by inhibiting alkaline phosphatase (ALPL). The study provides a potential strategy candidate or targeted dietary patterns to prevent and treat AD by improving the BBB function.
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Enfermedad de Alzheimer , Euphausiacea , Enfermedades Neurodegenerativas , Ratones , Animales , Barrera Hematoencefálica , Fosfatasa Alcalina/metabolismo , Fosfatasa Alcalina/farmacología , Fosfatasa Alcalina/uso terapéutico , Ligandos , Células Endoteliales/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Encéfalo/metabolismo , Transcitosis , Proteínas Portadoras/metabolismo , Enfermedad de Alzheimer/metabolismoRESUMEN
Previous studies have found that eicosapentaenoic acid-enriched phospholipids (EPA-PLs) alleviated glucose and lipid metabolism, which was accompanied by an increase of cluster of differentiation 36 (CD36). However, the effects of EPA-PLs on glucose and lipid metabolism in the case of CD36 mutation are unclear. Thus, spontaneously hypertensive rats/NCrl (SHR) were used as a CD36 mutation model to determine the effects of dietary 2% EPA-PLs for 4 weeks on glucose and lipid metabolism. The results showed that the intervention of EPA-PLs significantly alleviated the abnormal increase of serum free fatty acid levels and glycerol levels in SHRs. Moreover, the administration of EPA-PLs decreased the triglyceride levels and cholesterol levels by 31.1% and 37.9%, respectively, in the liver. Dietary EPA-PLs had no effect on epididymal fat weight, but EPA-PLs inhibited adipocyte hypertrophy in SHRs. Further mechanistic research found that EPA-PL pretreatment significantly reduced triacylglycerol catabolism and increased fatty acid ß-oxidation. Additionally, the administration of EPA-PLs decreased the area under the curve of the intraperitoneal glucose tolerance test and fasting serum insulin levels by activating the IRS/PI3K/AKT signaling pathway. Furthermore, EPA-PL pretreatment significantly increased the CD36 gene expression in the liver tissues, adipose tissues and muscle tissues even in the case of CD36 mutation. These results indicated that EPA-PLs alleviate glucose and lipid metabolism in the case of CD36 mutation, which provides a precise nutrition strategy for people with CD36 mutation.
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Glucosa , Metabolismo de los Lípidos , Ratas , Animales , Glucosa/metabolismo , Ratas Endogámicas SHR , Fosfolípidos/metabolismo , Ácido Eicosapentaenoico/farmacología , Fosfatidilinositol 3-Quinasas/metabolismoRESUMEN
SCOPE: It has been reported that eicosapentaenoic acid (EPA), especially EPA-enriched phospholipids (EPA-PL), significantly ameliorates depression-like behavior in mice, while the corresponding effect of docosahexaenoic acid (DHA) is weak. However, it is still unclear whether the limited effect of DHA on alleviating depression is remedied by dose and chemical structure adjustment to DHA-PL. METHODS AND RESULTS: A mouse model with depression is established by chronic unpredictable mild stress (CUMS) coupled with lipopolysaccharide (LPS) challenge to simulate the infection-triggered immune perturbation during chronic stress, and the effects of dietary 0.2% EPA-PL, 0.2% DHA-PL, 0.6% DHA-PL, and 0.6% DHA-enriched ethyl ester (DHA-EE) are comparatively investigated. The results demonstrate that dietary 0.6% DHA-PL, instead of 0.2% DHA-PL and 0.6% DHA-EE, significantly rescues the depression-like behavior with similar effects to 0.2% EPA-PL. Further studies reveal that dietary DHA-PL regulates immune dysregulation, inhibits neuroinflammation by NLRP3 inflammasome, and further improves monoamine systems and the hypothalamic-pituitary-adrenal (HPA) axis. CONCLUSION: The limited effect of DHA on depression is remedied by chemical structure adjustment to DHA-PL and three-fold dose. The present findings provide a potential novel candidate or targeted dietary patterns to prevent and treat depression.
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Ácidos Docosahexaenoicos , Fosfolípidos , Ratones , Animales , Fosfolípidos/farmacología , Ácidos Docosahexaenoicos/farmacología , Ácido Eicosapentaenoico/farmacología , Ácido Eicosapentaenoico/química , Dieta , Relación Estructura-ActividadRESUMEN
As an oxycarotenoid with strong antioxidant properties, astaxanthin can considerably boost pigmentation and improve the nutritional value of eggs. The purpose of this study was to elucidate the comparative effects of different chemical structures of astaxanthin including free astaxanthin, monoester-enriched astaxanthin and diester-enriched astaxanthin on the nutritional enhancement of eggs within 20 days. The results showed that supplementation of free astaxanthin to laying hens was more effective in accumulating astaxanthin in egg yolks than supplementation with esterified astaxanthin. The retention rate of free astaxanthin was approximately 12.0 % at the plateau phase in egg yolk, while that of monoester-enriched and diester-enriched astaxanthin were 4.0 % and 2.5 %, respectively. Free astaxanthin possessed a high retention rate and pigmentation effect compared with esterified astaxanthin, which might provide a basis for astaxanthin enhancement in eggs and potential application in nutritional functional foods.
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Pollos , Yema de Huevo , Animales , Femenino , Yema de Huevo/química , Alimentación Animal/análisis , Dieta , HuevosRESUMEN
BACKGROUND: Sea cucumber saponins (SCSs) exhibit a unique structure and high bioactivities and might have specialized implications on caffeine metabolic process by altering the activity of N-demethylation enzyme CYP1A2. The present study aimed to clarify the effects of SCS on caffeine metabolism in vivo and in vitro, as well as the synergistic anti-obesity effect of SCS and caffeine on high-fat diet-induced obese mice. RESULTS: Results found that SCS administration significantly postponed the elimination rate of caffeine and its metabolites in vivo, and further study found CYP1A2-mediated caffeine metabolism was remarkably inhibited in a dose-dependent manner in vitro. The synergistic effect of the SCS and caffeine combination could decrease the total weight of white adipose tissue by 52% compared with high-fat diet-treated group. CONCLUSION: SCS could prolong caffeine action time, and the combination of the two substances exhibited joint action on high-fat diet-induced obese mice. These findings might provide a basis for the development of functional foods and potential application using the combination of SCS and caffeine. © 2022 Society of Chemical Industry.
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Saponinas , Pepinos de Mar , Ratones , Animales , Saponinas/química , Dieta Alta en Grasa , Cafeína , Citocromo P-450 CYP1A2/metabolismo , Pepinos de Mar/química , Pepinos de Mar/metabolismo , Ratones Obesos , Obesidad/prevención & controlRESUMEN
Docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) play an important role in maintaining the physiological functions of tissues, and the beneficial effects of DHA/EPA in phospholipid forms have been widely reported. Although lysophosphatidylcholine (LPC) is considered to be the preferred form of DHA supplementation for the brain, the kinetics of DHA and EPA recovery and corresponding changes of n-6 docosapentaenoic acid (DPA) and arachidonic acid (AA) levels in different phospholipid molecules and different tissues after administration of EPA in phosphatidylcholine (PC) and LPC forms and DHA in the LPC form are not clear. Here, we measured the total fatty acids in tissues and fatty acid composition of different phospholipid molecules after gavage administration of equal molar amounts of EPA/DHA in mice with n-3 polyunsaturated fatty acid (PUFA) deficiency induced by maternal dietary deprivation of n-3 PUFA during pregnancy and lactation. The results showed that dietary supplementation with EPA-PC, EPA-LPC, and DHA-LPC exhibited different priorities for EPA or DHA accretion and supplementation efficiency curves in different tissues during the developing period. EPA-PC exhibited a more optimal efficacy in DHA and EPA repletion in serum and hepatic total fatty acids. In terms of DHA recovery in the brain, EPA-LPC and DHA-LPC showed great effects. Meanwhile, the DHA level in total fatty acids and major fractions of phospholipids (PC, PE, and PI + PS) in the heart and bone marrow with the supplementation of DHA-LPC displayed a relatively considerable increase compared with that of EPA supplementation groups. The study provides a reference for the time course of DHA or EPA recovery in phospholipid molecular species in different tissues after the supplementation of EPA-PC, EPA-LPC, and DHA-LPC.
Asunto(s)
Ácido Eicosapentaenoico , Ácidos Grasos Omega-3 , Embarazo , Femenino , Ratones , Animales , Ácidos Docosahexaenoicos/farmacología , Lisofosfatidilcolinas , Fosfolípidos/análisis , Ácido Araquidónico , Ácidos Grasos/análisis , LecitinasRESUMEN
The complex pathogenesis of Alzheimer's disease (AD) leads to a limited therapeutic effect; therefore, the combination of multiple bioactive ingredients may be more effective in improving AD due to synergistic effects. Based on the perspective of the sea-land combination, the effects of sea-derived Antarctic krill oil (AKO) combined with land-derived nobiletin (Nob) and L-theanine (The) on memory loss and cognitive deficiency were studied in senescence-accelerated prone 8 mice (SAMP8). The results demonstrated that AKO combined with The significantly increased the number of platform crossings in the Morris water maze test by 1.6-fold, and AKO combined with Nob significantly increased the preference index in a novel object recognition test. AKO exhibited synergistic effects with Nob and The in ameliorating recognition memory and spatial memory deficiency in SAMP8 mice, respectively. Further research of the mechanism indicated that AKO exhibited synergistic effects with Nob in suppressing ß-amyloid (Aß) aggregation, neurofibrillary tangles, and apoptosis and neuroinflammation, while the synergistic effects of AKO and The involved in synaptic plasticity and anti-neuroinflammation, which revealed that the combination was complex, not a mechanical addition. These findings revealed that the sea-land combination may be an effective strategy to treat and alleviate AD.