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1.
Eur J Nutr ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38867083

RESUMEN

PURPOSE: DNA methylation is a major epigenetic phenomenon through which diet affects health and disease. This study aimed to determine the epigenetic influence of the traditional Korean diet (K-diet) on global DNA methylation via one-carbon metabolism. METHODS: A crossover study was conducted on 52 women. Two diets, a K-diet, high in plant foods and low in calories and animal fat, and a control diet, similar to the diet currently consumed in Korea, were provided to all subjects alternately for 4 weeks with a 4-week washout period. Clinical parameters were measured before and after each dietary intervention. Nutrient intake was calculated by using a computer-aided nutritional analysis program. One-carbon metabolites in the serum and global DNA methylation in peripheral mononuclear cells were determined using ultra-performance liquid chromatography-tandem mass spectrometry. RESULTS: The K-diet group consumed more folate (669.9 ± 6.7 µg vs. 502.7 ± 3.0, p < 0.001), B6, B12, serine, and choline, and less methionine (992.6 ± 63 vs. 1048.3 mg ± 34.1, p < 0.0001) than the control group did. In the K-diet group, the increment of plasma 5-methyltetrahydrofolate (0.08 µg/mL ± 0.11 vs 0.02 ± 0.10, p < 0.009) and decrement of L-homocysteine (- 70.7 ± 85.0 vs - 39.3 ± 69.4, p < 0.0168) were greater than those of the control group. Global DNA methylation was significantly increased in the K-diet group (6.70 ± 3.02% to 9.45 ± 3.69, p < 0.0001) but not in the control group. CONCLUSIONS: A K-diet high in one-carbon nutrients can enhance the global DNA methylation status, suggesting an epigenetic mechanism by which the K-diet conveys health effects. Trial registration Korean Clinical Trial Registry (trial number: KCT0005340, 24/08/2020, retrospectively registered).

2.
Nutr Neurosci ; : 1-9, 2024 Aug 19.
Artículo en Inglés | MEDLINE | ID: mdl-39159004

RESUMEN

Throughout history, various cultures have recognized the significance of insects and have integrated them into traditional medicinal practices. In addition to medicines, insects are garnering attention as a sustainable and nutritious dietary alternative. Although edible insects have long been recognized as food sources in many Asian cultures, recent scientific studies have highlighted their potential therapeutic benefits, particularly in the field of neuroprotection. This review explores insect-derived extracts and peptides, elucidating their neuroprotective potential. This review highlights the potential use of insects as a source of neuroprotective agents. Advancements in neuroprotection may find a key ally in insects as our understanding of the symbiotic relationship between insects and human health becomes more profound.

3.
BMC Vet Res ; 20(1): 133, 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38570815

RESUMEN

BACKGROUND: Obesity is a serious disease with an alarmingly high incidence that can lead to other complications in both humans and dogs. Similar to humans, obesity can cause metabolic diseases such as diabetes in dogs. Natural products may be the preferred intervention for metabolic diseases such as obesity. The compound 1-deoxynojirimycin, present in Morus leaves and other sources has antiobesity effects. The possible antiobesity effect of 1-deoxynojirimycin containing Morus alba leaf-based food was studied in healthy companion dogs (n = 46) visiting the veterinary clinic without a history of diseases. Body weight, body condition score (BCS), blood-related parameters, and other vital parameters of the dogs were studied. Whole-transcriptome of blood and gut microbiome analysis was also carried out to investigate the possible mechanisms of action and role of changes in the gut microbiome due to treatment. RESULTS: After 90 days of treatment, a significant antiobesity effect of the treatment food was observed through the reduction of weight, BCS, and blood-related parameters. A whole-transcriptome study revealed differentially expressed target genes important in obesity and diabetes-related pathways such as MLXIPL, CREB3L1, EGR1, ACTA2, SERPINE1, NOTCH3, and CXCL8. Gut microbiome analysis also revealed a significant difference in alpha and beta-diversity parameters in the treatment group. Similarly, the microbiota known for their health-promoting effects such as Lactobacillus ruminis, and Weissella hellenica were abundant (increased) in the treatment group. The predicted functional pathways related to obesity were also differentially abundant between groups. CONCLUSIONS: 1-Deoxynojirimycin-containing treatment food have been shown to significantly improve obesity. The identified genes, pathways, and gut microbiome-related results may be pursued in further studies to develop 1-deoxynojirimycin-based products as candidates against obesity.


Asunto(s)
Diabetes Mellitus , Enfermedades de los Perros , Microbioma Gastrointestinal , Enfermedades Metabólicas , Morus , Humanos , Animales , Perros , 1-Desoxinojirimicina/farmacología , Extractos Vegetales/farmacología , Obesidad/tratamiento farmacológico , Obesidad/veterinaria , Diabetes Mellitus/veterinaria , Enfermedades Metabólicas/veterinaria , Hojas de la Planta
4.
Mar Drugs ; 22(1)2024 Jan 17.
Artículo en Inglés | MEDLINE | ID: mdl-38248672

RESUMEN

Macroalgae, particularly red seaweeds, have attracted significant attention due to their economic and health benefits. Chondrus, a red algae genus, despite its economic importance, seems to be undervalued. Among all its species, Chondrus crispus has been meticulously documented for its biological properties, and little is known about other species. No comprehensive review of the biological properties of this genus has been acknowledged. Thus, this review aimed to summarize the available information on the chemical constituents and biological properties of a few selected species, including Chondrus crispus, Chondrus ocellatus, Mazzaella canaliculata, and Chondrus armatus. We compiled and discovered that the genus is offering most of the important health-promoting benefits evidenced from in vitro and in vivo studies focused on antimicrobial, immunomodulation, neuroprotection, anti-atopic, anti-inflammatory, anti-viral, anti-diabetic, cytoprotective, antioxidant, anti-coagulation, nephroprotective, anti-tumor, and anti-venom activity, which speaks about the potential of this genus. Data on clinical studies are limited. Further, around 105 chemical constituents have been reported from Chondrus spp. Given its significance, further investigation is warranted, in the form of meticulously planned cell, animal, and clinical studies that concentrate on novel health-enhancing endeavors, in order to unveil the full potential of this genus. The review also outlines challenges and future directions.


Asunto(s)
Chondrus , Hipersensibilidad Inmediata , Algas Marinas , Animales , Antioxidantes/farmacología , Antivenenos
5.
Int J Mol Sci ; 25(5)2024 Feb 23.
Artículo en Inglés | MEDLINE | ID: mdl-38473839

RESUMEN

Leopoldia comosa (LC), popularly known as Muscari comosum, spontaneously grows in the Mediterranean region and its bulbs are used as a vegetable. Traditionally, they are also used to treat various diseases and conditions, which has inspired the study of the pharmacological activities of different parts of LC. These studies revealed the numerous biological properties of LC including antioxidant, anti-inflammatory, anti-diabetes, anti-obesity, anti-cancer, anti-Alzheimer's disease, antibacterial, and immune stimulant. High antioxidant activity compared to other non-cultivated plants, and the potential role of antioxidant activity in other reported activities make LC an excellent candidate to be developed as an antioxidant plant against important associated diseases. The presence of a diverse class of phytochemicals (n = 85), especially flavonoids and homoisoflavones, in LC, also imparts significance to the nutraceutical candidature of the plant. However, limited animal studies and the lack of a directional approach have limited the further design of effective clinical studies for the development of LC. The current study is the first attempt to comprehensively compile information regarding the phytochemicals and pharmacological activities of LC, emphasize the targets/markers targeted by LC, important in other activities, and also highlight the current gaps and propose possible bridges for the development of LC as a therapeutic and/or supplement against important diseases.


Asunto(s)
Antioxidantes , Asparagaceae , Animales , Antioxidantes/farmacología , Extractos Vegetales/farmacología , Flavonoides/farmacología , Fitoquímicos/farmacología
6.
Molecules ; 29(1)2023 Dec 28.
Artículo en Inglés | MEDLINE | ID: mdl-38202771

RESUMEN

Shionone is a triterpenoid that is the primary constituent of an important ancient Chinese medicine named Radix Asteris. It has emerged as an attractive candidate against different important diseases, including interstitial cystitis, colitis, cancer, Parkinson's disease, and urinary tract infections, and was found to have a protective effect on multiple organs, including the colon, kidneys, lungs, brain, and bladder. The anti-inflammation activity of shionone may be considered an important property that imparts the positive health outcomes of shionone. Important molecular targets and markers such as TNF-α, STAT3, NLRP3, and NF-κB were also found to be targeted by shionone and were verified in different diseases. This suggests the possible potential of shionone against other diseases associated with these targets. Pharmacokinetic studies also support the therapeutic potential of shionone and provide the initial track that may be pursued for its development. Yet, the compilation of the pharmacological activities of shionone and its important genes and pathway targets are absent in the existing literature, which would direct its development as a therapeutic and/or supplement. Hence, the present review provides a compilation of information concerning pharmacological activities, highlights the existing holes, and proposes a specific direction for the expansion of shionone as a therapeutic against different diseases and conditions.


Asunto(s)
Antiinflamatorios , Fitoquímicos , Triterpenos , Humanos , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Triterpenos/farmacología , Triterpenos/uso terapéutico , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico
7.
Nutrients ; 16(12)2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38931173

RESUMEN

Depression represents a widespread and devastating psychiatric public health challenge globally. It is particularly prevalent among young adults in Korea. Certain foods may have medicinal properties that alleviate depressive symptoms. This study aimed to examine the association between specific foods and depressive symptoms among young adults, exploring their bioactive effects and possible mechanisms. We conducted a cross-sectional study involving 1000 Korean young adults aged 18-39 years. Food frequency questionnaires were used to assess diets and their associations with depressive symptoms. Results from multivariable logistic regression analysis indicated associations between several specific foods and their effects: milk (odds ratio = 0.58, 95% confidence interval: 0.36-0.94), eggs (0.55, 0.35-0.87), bananas (0.58, 0.36-0.94), oranges (0.62, 0.40-0.96), sweet potatoes (0.60, 0.37-0.97), mushrooms (0.53, 0.31-0.92, females only), and kimchi (0.40, 0.17-0.95, males only). Furthermore, molecular docking indicated that hesperidin had the highest docking score of 5.86 in oranges. Several bioactive compounds identified as potentially beneficial in combatting depression include calcium, casein, alpha-lactalbumin, tryptophan (TRP), vitamin B6 and B12, magnesium, flavonoids (especially hesperidin), carotenoids, ergothioneine, fiber, and probiotics. To recommend these foods in the management of depression among young adults, further clinical intervention studies are necessary.


Asunto(s)
Depresión , Humanos , Femenino , Adulto Joven , Masculino , Adulto , Estudios Transversales , Adolescente , República de Corea , Dieta , Simulación del Acoplamiento Molecular
8.
Nutrients ; 16(6)2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38542687

RESUMEN

Depressive symptoms are a common menopausal feature in middle-aged women and are associated with dietary factors. This study aimed to determine the association between dietary patterns and depressive symptoms in 2190 Korean women aged 45-69 years. Depressive symptoms were screened using the Beck Depression Inventory-II (BDI-II), and food intake was examined using a food frequency questionnaire. Dietary patterns were derived from principal components analysis and identified two dietary patterns: a "healthy" dietary pattern (high intake of whole-grain rice, legumes, vegetables, fruits, and fish) and an "unhealthy" dietary pattern (high intake of noodles, dumplings, sweets, red meat, soda, and coffee). After adjusting for all confounding factors, those with the highest healthy dietary pattern scores had a 0.56-fold lower risk of depressive symptoms than those with the lowest score (Odds Ratio (OR) = 0.56, 95% confidence interval (CI): 0.37-0.84, p for trend = 0.006). Conversely, those with the highest unhealthy pattern scores had a 1.85-fold higher risk of depressive symptoms than that of those in the lowest quartile (OR = 1.85, 95% CI: 1.30-2.63, p for trend = 0.002). In middle-aged women, a dietary pattern of high intake of fiber-rich whole-grain rice, fruits, vegetables, and legumes may help prevent and manage depressive symptoms.


Asunto(s)
Depresión , Dieta , Persona de Mediana Edad , Animales , Humanos , Femenino , Depresión/epidemiología , Patrones Dietéticos , Verduras , Frutas , Conducta Alimentaria
9.
Heliyon ; 10(13): e33572, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-39040249

RESUMEN

The extensive utilization of bismuth and its derivatives in many industries, such as chemical, semiconductor, pharmaceutical, and cosmetics, leads to their accumulation in wastewater, posing a risk to both human health and the environment. Carbon nanorods (CNR) are fluorescent nanoparticles with an ability to detect various analytes as sensing probes. This study focuses on the production, structure, and chemical composition characterization of silkworm-derived CNR (swCNR) and their ability to detect bismuth ions (Bi3+) and inhibit radicals. The optimum wavelength for exciting the fluorescence of swCNR was 370 nm, and the resulting emission peak was observed at 436 nm. The prepared swCNR showed static fluorescence quenching mechanism-based sensing of Bi3+ ions with a limit of detection of 175 nM and two linear ranges from 0.5 to 5 µM (R2 = 0.9997) and 10-50 µM (R2 = 0.9995). The swCNR demonstrated high selectivity in detecting Bi3+ ions in the spiked river water samples, thus establishing the swCNR's role as a nano fluorescence probe designed for the selective detection of Bi3+ ions among other metal ions. Favorable results for the antiradical ability of swCNR were obtained against hydroxyl, 2,2 diphenyl-1 picrylhydrazyl, and 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) radicals with scavenging percentages of 15, 32, and 90, respectively. The possible applications of swCNR in the environmental and antioxidant sectors are proposed in this study.

10.
Redox Biol ; 73: 103197, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38781730

RESUMEN

Astrocytes are the major glial cells in the human brain and provide crucial metabolic and trophic support to neurons. The amyloid-ß peptide (Aß) alter the morphological and functional properties of astrocytes and induce inflammation and calcium dysregulation, contributing to Alzheimer's disease (AD) pathology. Recent studies highlight the role of Toll-like receptor (TLR) 4/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) signaling in inflammation. Reactive oxygen species (ROS) generated due to Aß, induce apoptosis in the brain cells worsening AD progression. Astrocytic cell surface receptors, such as purinergic receptors (P2Y1 and P2Y2), metabotropic glutamate receptor (mGLUR)5, α7 nicotinic acetylcholine receptor (α7nAChR), and N-methyl-d-aspartate receptors (NMDARs), have been suggested to interact with inositol trisphosphate receptor (IP3R) on the endoplasmic reticulum (ER) to induce Ca2+ movement from ER to cytoplasm, causing Ca2+ dysregulation. We found that the citrus flavonoid nobiletin (NOB) protected primary astrocytes from Aß42-induced cytotoxicity and inhibited TLR4/NF-κB signaling in Aß42-induced primary rat astrocytes. NOB was found to regulate Aß42-induced ROS levels through Keap1-Nrf2 pathway. The receptors P2Y1, P2Y2, mGLUR5, α7nAChR, and NMDARs induced intracellular Ca2+ levels by activating IP3R and NOB regulated them, thereby regulating intracellular Ca2+ levels. Molecular docking analysis revealed a possible interaction between NOB and IP3R in IP3R regulation. Furthermore, RNA sequencing revealed various NOB-mediated biological signaling pathways, such as the AD-presenilin, AD-amyloid secretase, and Wnt signaling pathway, suggesting possible neuroprotective roles of NOB. To conclude, NOB is a promising therapeutic agent for AD and works by modulating AD pathology at various levels in Aß42-induced primary rat astrocytes.


Asunto(s)
Péptidos beta-Amiloides , Astrocitos , Calcio , Flavonas , Receptores de Inositol 1,4,5-Trifosfato , Astrocitos/metabolismo , Astrocitos/efectos de los fármacos , Péptidos beta-Amiloides/metabolismo , Animales , Receptores de Inositol 1,4,5-Trifosfato/metabolismo , Ratas , Calcio/metabolismo , Flavonas/farmacología , Especies Reactivas de Oxígeno/metabolismo , Fragmentos de Péptidos/farmacología , Fragmentos de Péptidos/metabolismo , Enfermedades Neuroinflamatorias/metabolismo , Enfermedades Neuroinflamatorias/tratamiento farmacológico , Humanos , Transducción de Señal/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/tratamiento farmacológico , Enfermedad de Alzheimer/patología
11.
Animals (Basel) ; 14(9)2024 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-38731333

RESUMEN

The seafood processing industry generates significant waste, including mackerel heads (MH), constituting 20-32% of total waste. This study explored the potential of utilizing MH as a feed source for black soldier fly larvae (BSF larvae). BSF larvae are known for their ability to efficiently convert organic materials into nutrient-rich biomass. Five concentrations of MH (0, 10, 20, 30, 40, and 50% in chicken feed) were fed to BSF larvae for eight days. After harvesting, their growth, MH conversion efficiency, nutritional content, and heavy metals reduction potential were measured. BSF larvae showed optimal growth when fed with a feed containing 20% MH, resulting in a 14.36-fold increase in weight compared to the control group, as determined by the Fisher's Least Significant Difference Test. BSF larvae maintained a survival rate of 99.33%. With the lowest feed conversion ratio (FCR) of 2.09 at 20% MH, feed efficiency was improved by up to 65.15%, and feed reduction up to 73.53%. MH enhanced lipid and protein content in BSF larvae. Furthermore, BSF larvae in this study showed higher polyunsaturated fatty acids (PUFA), including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), as well as other amino acids which are required for breeding animals. The current study highlights the potential of MH as a feed source for BSF larvae, improving nutritional biomass. It also suggests BSF larvae as an eco-friendly option for handling seafood processing waste and as an alternative feed source for animals.

12.
Toxicol Res ; 40(1): 153-161, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38223674

RESUMEN

Parabens are used as preservatives in various household products, including oral products, cosmetics, and hair/body washes. In recent years, the widespread use of parabens has raised concerns due to the potential health risks associated with their estrogenic effects. In the present study, we evaluated and compared the estrogenic activity of parabens using two cell-based in vitro tests: (1) bioluminescence resonance energy transfer (BRET)-based estrogen receptor alpha (ERα) dimerization using HEK293 cells that were stably transfected with ERα-fused NanoLuc luciferase (Nluc) and HaloTag (HT) expression vector, and (2) stably transfected transcriptional activation (STTA) assays using ERα-HeLa9903 cells. The following parabens were tested using the BRET-based ERα dimerization assay and showed estrogenic activity (PC20 values): methyl paraben (MP, 5.98 × 10-5 M), ethyl paraben (EP, 3.29 × 10-5 M), propylparaben (PP, 3.09 × 10-5 M), butyl paraben (BP, 2.58 × 10-5 M), isopropyl paraben (IsoPP, 1.37 × 10-5 M), and isobutyl paraben (IsoBP, 1.43 × 10-5 M). Except MP, all other parabens tested using the STTA assay also showed estrogenic activity: EP, 7.57 × 10-6 M; PP, 1.18 × 10-6 M; BP, 3.02 × 10-7 M; IsoPP, 3.58 × 10-7 M; and IsoBP, 1.80 × 10-7 M. Overall, EP, PP, BP, IsoPP, and IsoBP tested positive for estrogenic activity using both assays. These findings demonstrate that most parabens, albeit not all, induce ERα dimerization and possess estrogenic activity.

13.
Epidemiol Health ; 46: e2024042, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38574826

RESUMEN

This study presents the nutrition survey methods and the updated food composition database for the Korean Genome and Epidemiology Study (KoGES). The KoGES, which is the largest and longest cohort study in Korea, aims to identify genetic and environmental factors associated with chronic diseases. This study has collected dietary data using a validated semi-quantitative food frequency questionnaire and/or the 24-hour recall method. However, these dietary survey methods use different food composition databases, and their nutritional values are out of date. Therefore, it became necessary to update the food composition database by revising nutrient analysis values to reflect improvements in the performance of food ingredient analysis equipment, revising international values to analysis values of Korean agricultural products, adjusting nutrient units, and adding newly reported nutrients related to chronic diseases. For this purpose, we integrated the different food composition databases used in each nutrition survey, updated 23 nutrients, and expanded 48 new nutrients for 3,648 food items using the latest reliable food composition databases published by national and international institutions. This revised food composition database may help to clarify the relationship between various nutrients and chronic diseases. It could serve as a valuable resource for nutritional, epidemiological, and genomic research and provide a basis for determining public health policies.


Asunto(s)
Bases de Datos Factuales , Encuestas Nutricionales , Humanos , República de Corea/epidemiología , Estudios de Cohortes
14.
Chemosphere ; 362: 142579, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38866337

RESUMEN

The growing number of companion dogs has contributed to a rapidly growing market for pet products, including dog toys. However, little is known about the hazardous substances released from dog toys. This study aims to examine the potential presence of obesogens, a subset of endocrine-disrupting chemicals (EDCs) that are widely utilized as raw materials in the manufacture of dog toy components, and their effects on dog health. To achieve this, we adapted and employed a migration method typically used for children's products to simulate obesogen exposure in dogs through sucking or chewing toys. We demonstrated that out of various obesogens, bisphenol A (BPA) was released from dog toys into synthetic saliva, whereas phthalates and azo dyes were not detected in any of the leachates. Additionally, we found that BPA induced adipogenic differentiation in canine adipose-derived stem cells (cADSCs). Our RNA sequencing experiments revealed that BPA alters the adipogenesis-related gene signature in cADSCs by elevating the expression levels of ADIPOQ, PLIN1, PCK1, CIDEC, and FABP4. The associated transcriptional changes are involved in the peroxisome proliferator-activated receptor (PPAR) signaling pathway, which may contribute to the promotion of adipogenesis by BPA. Our findings suggest that companion dogs are at risk of BPA exposure, which may contribute to obesity in dogs. Therefore, the implementation of precautionary measures is crucial.


Asunto(s)
Adipogénesis , Compuestos de Bencidrilo , Disruptores Endocrinos , Obesidad , Fenoles , Células Madre , Animales , Perros , Compuestos de Bencidrilo/toxicidad , Fenoles/toxicidad , Adipogénesis/efectos de los fármacos , Obesidad/metabolismo , Disruptores Endocrinos/toxicidad , Células Madre/efectos de los fármacos , Tejido Adiposo/metabolismo , Diferenciación Celular/efectos de los fármacos
15.
Int Immunopharmacol ; 139: 112677, 2024 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-39024753

RESUMEN

High-molecular-weight fucoidan (Fucoidan P), sourced from Undaria pinnatifida exhibits several health benefits, including immunomodulation. However, the mechanisms underlying the immune-enhancing effects of Fucoidan P remain unclear. Here, we investigated the immune-enhancing effects and the potential mechanisms of Fucoidan P using RAW 264.7 macrophages and cyclophosphamide (CP)-induced immunosuppression rat model. In macrophages, Fucoidan P showed dose-dependent stimulation by increasing cell proliferation, nitric oxide production, and gene expression of inducible nitric oxide synthase, cyclooxygenase-2, and proinflammatory cytokines. These effects are mediated through the activation of the nuclear factor-kappa B (NF-κB) signaling pathway. Moreover, orally administered Fucoidan P was evaluated in immunosuppressed rats treated with CP. Fucoidan P administration increased hematological values and natural killer cell activity, and positively affected nitrite and prostaglandin E2 levels. The Fucoidan P treatment groups exhibited improved serum cytokine levels as well as splenic and intestinal cytokine mRNA expression compared to the model group. Fucoidan P also mitigated splenic damage and increased the phosphorylation of NF-κB and NF-κB inhibitor alpha (IκBα). Furthermore, Fucoidan P treatment altered the gut microbiota composition, enhancing the alpha diversity, evenness, and abundance of Bacteroidetes, which are associated with immune function. Taken together, our findings suggest that Fucoidan P exerts beneficial effects on immune function by activating NF-κB and modulating gut microbiota. These findings suggested its potential as a therapeutic agent for immune enhancement.


Asunto(s)
Ciclofosfamida , Citocinas , Microbioma Gastrointestinal , FN-kappa B , Polisacáridos , Animales , Polisacáridos/farmacología , Ratones , Microbioma Gastrointestinal/efectos de los fármacos , Células RAW 264.7 , Masculino , FN-kappa B/metabolismo , Ratas , Citocinas/metabolismo , Terapia de Inmunosupresión , Undaria/química , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Óxido Nítrico/metabolismo , Ratas Sprague-Dawley , Peso Molecular , Transducción de Señal/efectos de los fármacos , Bazo/efectos de los fármacos , Bazo/inmunología
16.
Cardiovasc Res ; 120(9): 1037-1050, 2024 Jul 31.
Artículo en Inglés | MEDLINE | ID: mdl-38722811

RESUMEN

AIMS: Doxorubicin (DOX) is a widely used anthracycline anticancer agent; however, its irreversible effects on the heart can result in DOX-induced cardiotoxicity (DICT) after cancer treatment. Unfortunately, the pathophysiology of DICT has not yet been fully elucidated, and there are no effective strategies for its prevention or treatment. In this investigation, the novel role of transducin beta-like protein 1 (TBL1) in developing and regulating DICT was explored. METHODS AND RESULTS: We observed a reduction in TBL1 protein expression levels as well as cleavage events in the transplanted cardiac tissues of patients diagnosed with Dilated Cardiomyopathy and DICT. It was revealed that DOX selectively induces TBL1 cleavage at caspase-3 preferred sites-D125, D136, and D215. Interestingly, overexpression of the uncleaved TBL1 mutant (TBL1uclv) variant reduced apoptosis, effectively preventing DOX-induced cell death. We confirmed that cleaved TBL1 cannot form a complex with ß-catenin. As a result, Wnt reporter activity and Wnt target gene expression collectively indicate a decrease in Wnt/ß-catenin signalling, leading to DICT progression. Furthermore, the cleaved TBL1 triggered DOX-induced abnormal electrophysiological features and disrupted calcium homeostasis. However, these effects were improved in TBL1uclv-overexpressing human-induced pluripotent stem cell-derived cardiomyocytes. Finally, in a DICT mouse model, TBL1uclv overexpression inhibited the DICT-induced reduction of cardiac contractility and collagen accumulation, ultimately protecting cardiomyocytes from cell death. CONCLUSION: Our findings reveal that the inhibition of TBL1 cleavage not only mitigates apoptosis but also enhances cardiomyocyte function, even in the context of DOX administration. Consequently, this study's results suggest that inhibiting TBL1 cleavage may be a novel strategy to ameliorate DICT.


Asunto(s)
Apoptosis , Cardiotoxicidad , Doxorrubicina , Miocitos Cardíacos , Vía de Señalización Wnt , beta Catenina , Doxorrubicina/farmacología , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Miocitos Cardíacos/enzimología , Vía de Señalización Wnt/efectos de los fármacos , Humanos , Animales , Apoptosis/efectos de los fármacos , beta Catenina/metabolismo , beta Catenina/genética , Cardiomiopatía Dilatada/metabolismo , Cardiomiopatía Dilatada/patología , Cardiomiopatía Dilatada/inducido químicamente , Cardiomiopatía Dilatada/genética , Cardiomiopatía Dilatada/enzimología , Cardiomiopatía Dilatada/fisiopatología , Masculino , Transducina/metabolismo , Transducina/genética , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/enzimología , Células Madre Pluripotentes Inducidas/patología , Femenino , Estudios de Casos y Controles , Antibióticos Antineoplásicos/farmacología , Antibióticos Antineoplásicos/toxicidad
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