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Therapeutic Methods and Therapies TCIM
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1.
Int J Mol Sci ; 25(5)2024 Mar 03.
Article in English | MEDLINE | ID: mdl-38474201

ABSTRACT

In recent years, the potent influence of tocotrienol (T3) on diminishing blood glucose and lipid concentrations in both Mus musculus (rats) and Homo sapiens (humans) has been established. However, the comprehensive exploration of tocotrienol's hypolipidemic impact and the corresponding mechanisms in aquatic species remains inadequate. In this study, we established a zebrafish model of a type 2 diabetes mellitus (T2DM) model through high-fat diet administration to zebrafish. In the T2DM zebrafish, the thickness of ocular vascular walls significantly increased compared to the control group, which was mitigated after treatment with T3. Additionally, our findings demonstrate the regulatory effect of T3 on lipid metabolism, leading to the reduced synthesis and storage of adipose tissue in zebrafish. We validated the expression patterns of genes relevant to these processes using RT-qPCR. In the T2DM model, there was an almost two-fold upregulation in pparγ and cyp7a1 mRNA levels, coupled with a significant downregulation in cpt1a mRNA (p < 0.01) compared to the control group. The ELISA revealed that the protein expression levels of Pparγ and Rxrα exhibited a two-fold elevation in the T2DM group relative to the control. In the T3-treated group, Pparγ and Rxrα protein expression levels consistently exhibited a two-fold decrease compared to the model group. Lipid metabolomics showed that T3 could affect the metabolic pathways of zebrafish lipid regulation, including lipid synthesis and decomposition. We provided experimental evidence that T3 could mitigate lipid accumulation in our zebrafish T2DM model. Elucidating the lipid-lowering effects of T3 could help to minimize the detrimental impacts of overfeeding in aquaculture.


Subject(s)
Diabetes Mellitus, Type 2 , Hyperlipidemias , Tocotrienols , Humans , Mice , Rats , Animals , Tocotrienols/metabolism , Zebrafish/metabolism , Diet, High-Fat , Hyperlipidemias/metabolism , Rice Bran Oil , Diabetes Mellitus, Type 2/metabolism , PPAR gamma/metabolism , RNA, Messenger/metabolism , Lipid Metabolism , Liver/metabolism
2.
Fish Shellfish Immunol ; 136: 108740, 2023 May.
Article in English | MEDLINE | ID: mdl-37061070

ABSTRACT

Tocotrienols have strong antioxidant properties; however, tocotrienol has not been investigated in detail in aquatic products. In this study, the anti-inflammatory and antioxidant activities of the tocotrienol-rich fraction from rice bran oil and its potential mechanism were verified in a zebrafish CuSO4 inflammation model. The in vitro antioxidant activity was evaluated using the 2,2-Diphenyl-1-picrylhydrazyl (DPPH) stable radical method. The copper chelating activity was determined using the pyrocatechol violet method. Intracellular reactive oxygen species in zebrafish were detected using a fluorescent ROS probe. Transgenic Tg (lyz: DsRed2) zebrafish were used for neutrophil transmigration assays. The mRNA expression levels of antioxidant and pro-inflammatory factor genes were measured using quantitative real-time reverse transcription PCR. In the concentration range tested, 100 µg/mL TRF had the highest copper chelating activity (10%). TRF showed DPPH-free radical scavenging ability, which was 53% at 100 µg/mL TRF. TRF effectively repressed ROS generation and inhibited neutrophil migration to the inflamed site. Moreover, TRF upregulated the expression of antioxidant genes sod and gpx4b, inhibited the expression of pro-inflammatory factors tnfa and il8, and suppressed CuSO4-induced inflammation. In conclusion, TRF has significant anti-inflammatory and antioxidant properties, which supports the use of TRF as an aquatic feed additive to improve the anti-inflammatory and antioxidant capacity of aquatic products.


Subject(s)
Antioxidants , Tocotrienols , Animals , Antioxidants/pharmacology , Rice Bran Oil , Zebrafish , Tocotrienols/pharmacology , Copper Sulfate , Reactive Oxygen Species , Copper , Anti-Inflammatory Agents/pharmacology , Inflammation/chemically induced
3.
J Clin Gastroenterol ; 48(9): 790-5, 2014 Oct.
Article in English | MEDLINE | ID: mdl-24440935

ABSTRACT

GOALS: To examine the efficiency of exclusive enteral nutrition (EEN) in relieving inflammatory bowel stricture in patients with Crohn's disease (CD). BACKGROUND: Patients with CD usually develop bowel strictures due to transmural edema of intestinal wall, which can potentially be managed with conservative medical treatment. Previous studies showed that EEN therapy could induce clinical remission through its anti-inflammation effect. METHODS: We achieved a prospective observational study. CD patients with inflammatory bowel stricture were preliminarily differentiated from a fibrous one, and further treated with EEN therapy for 12 weeks. Demographics and clinical variables were recorded. Nutritional (body mass index, albumin, pre-albumin, transferrin, etc.), inflammatory (C-reactive protein, erythrocyte sedimentation rate, white blood cell, etc.), and radiologic parameters (bowel wall thickness, luminal diameter, and luminal cross-sectional area) were evaluated at baseline, week 4, and week 12, respectively. RESULTS: Between May 2012 and January 2013, 65 patients with CD were preliminarily diagnosed with inflammatory bowel stricture and 6 patients were further excluded. Among the remaining 59 cases, 50 patients (84.7%) finished the whole EEN treatment, whereas the other 9 patients (15.3%) gained progressive bowel obstruction resulting in surgery. Intention-to-treat analyses showed that 48 patients (81.4%) achieved symptomatic remission, 35 patients (53.8%) achieved radiologic remission, and 42 patients (64.6%) achieved clinical remission. Among those patients who complete the whole EEN therapy, inflammatory, nutritional, and radiologic parameters improved significantly compared with baseline. Of note, the average luminal cross-sectional area at the site of stricture increased approximately 331% at week 12 (195.7 ± 18.79 vs. 59.09 ± 10.64 mm, P<0.001). CONCLUSIONS: EEN therapy can effectively relieve inflammatory bowel stricture in CD, which replenishes roles of enteral nutrition in the treatment of CD. Further studies are expected to investigate the underlying mechanisms of this effect in the future.


Subject(s)
Crohn Disease/therapy , Enteral Nutrition/methods , Intestinal Obstruction/therapy , Adult , Crohn Disease/diagnostic imaging , Female , Humans , Intestinal Obstruction/diagnostic imaging , Male , Prospective Studies , Radiography , Treatment Outcome
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