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Obesity is a global health crisis, marked by excessive fat in tissues that function as immune organs, linked to microbiota dysregulation and adipose inflammation. Investigating the effects of Lactobacillus rhamnosus SG069 (LR069) and Lactobacillus brevis SG031 (LB031) on obesity and lipid metabolism, this research highlights adipose tissue's critical immune-metabolic role and the probiotics' potential against diet-induced obesity. Mice fed a high-fat diet were treated with either LR069 or LB031 for 12 weeks. Administration of LB031 boosted lipid metabolism, indicated by higher AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) phosphorylation, and increased the M2/M1 macrophage ratio, indicating LB031's anti-inflammatory effect. Meanwhile, LR069 administration not only led to significant weight loss by enhancing lipolysis which evidenced by increased phosphorylation of hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) but also elevated Akkermansia and fecal acetic acid levels, showing the gut microbiota's pivotal role in its antiobesity effects. LR069 and LB031 exhibit distinct effects on lipid metabolism and obesity, underscoring their potential for precise interventions. This research elucidates the unique impacts of these strains on metabolic health and highlights the intricate relationship between gut microbiota and obesity, advancing our knowledge of probiotics' therapeutic potential.
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Inflammatory bowel disease alters the gut microbiota, causes defects in mucosal barrier function, and leads to dysregulation of the immune response to microbial stimulation. This study investigated and compared the efficacy of a candidate probiotic strain, Bacillus coagulans BC198, and its heat-killed form in treating dextran sulfate sodium-induced colitis. Both live and heat-killed B. coagulans BC198 increased gut barrier-associated protein expression, reduced neutrophil and M1 macrophage infiltration of colon tissue, and corrected gut microbial dysbiosis induced by colitis. However, only live B. coagulans BC198 could alleviate the general symptoms of colitis, prevent colon shortening, and suppress inflammation and tissue damage. At the molecular level, live B. coagulans BC198 was able to inhibit Th17 cells while promoting Treg cells in mice with colitis, reduce pro-inflammatory MCP-1 production, and increase anti-inflammatory IL-10 expression in the colonic mucosa. The live form of B. coagulans BC198 functioned more effectively than the heat-killed form in ameliorating colitis by enhancing the anti-inflammatory response and promoting Treg cell accumulation in the colon.
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Arsenic (As) compounds can be classified as organic or inorganic, with inorganic arsenic (iAs) having significantly higher toxicity than organic As. As may accumulate in food materials that have been exposed to As-contaminated environments. Thus, the "Sanitation Standard for Contaminants and Toxins in Foods" published by the Ministry of Health and Welfare set the standard limits for iAs content in rice, seaweed, seafood, and marine oils to safeguard public health. Therefore, a robust analytical method must be developed to selectively and quantitatively determine iAs content in rice, seaweed, seafood, and marine oils. Herein, we reported and verified the method of combined high-performance liquid chromatography/inductively coupled plasma-mass spectrometry (HPLC/ICP-MS) to determine iAs content in a wide variety of food. The fish oil samples were spiked with different concentrations of the As(III) standard solution, and their iAs analyzes were obtained via extraction procedures using the 1% (w/w) nitric acid (HNO3) solution containing 0.2 M hydrogen peroxide (H2O2) under sonication. The extracts were subsequently analyzed for their As(V) contents using HPLC/ICP-MS with aqueous ammonium carbonate as the mobile phase. The As(III) species had completely oxidized into the As(V) species, which prevented interferences between organic and iAs during chromatography. The method showed good extraction efficiencies (generally >90%) for the iAs samples, and their limits of quantification in fish oil were 0.02 mg/kg. The method was verified via the iAs speciation analytes of rice, seaweed, seafood, and marine oil matrices. The average recoveries for the fortified samples of each matrix ranged from 87.5 to 112.4%, with their coefficients of variation being less than 10%. Surveillance studies were conducted on the iAs contents of food samples purchased from local Taiwanese markets. The results showed that the only Hijiki (Sargassum fusiforme) higher than the maximum limit of the sanitation standard for iAs in seaweed, whereas the remaining samples met their corresponding requirements. This method is quick and straightforward, and it can be applied for the routine analysis of iAs content in a wide variety of food products to ensure public health safety.
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Arsénico , Arsenicales , Algas Marinas , Cromatografía Líquida de Alta Presión/métodos , Arsénico/análisis , Peróxido de Hidrógeno/análisis , Contaminación de Alimentos/análisis , Arsenicales/análisis , Arsenicales/química , Alimentos Marinos/análisis , Verduras , Algas Marinas/química , Análisis de los Alimentos/métodosRESUMEN
The major cause of death in colorectal cancer (CRC) patients is metastasis. Moreover, lots of studies have emphasized that the epithelial-mesenchymal transition (EMT) is a pivotal step in metastasis. Both transforming growth factor beta (TGF-ß) and dysregulation of microRNAs (miRNAs) can induce or regulate EMT, promoting the loss of intercellular adhesion and increased motility of cancer cells. Therefore, it is necessary to prevent or inhibit the metastasis of colorectal cancer. Relatively little is known about the anti-metastatic effect of oxyresveratrol (OXY), a natural derivative of resveratrol (RES), compared to RES. Accordingly, RES was used as the positive control to investigate the effects of OXY on colon cancer cell migration. The results showed that OXY could significantly inhibit cell migration (67.17% ± 0.04, 64.89% ± 0.04) compared to RES (84.6% ± 0.07, 76.34% ± 0.08) in HCT116 cells and TGF-ß-induced HT-29 cells, respectively, via Snail/E-cadherin expression. In addition, OXY improved EMT-related miRNA expression through, for example, lowering the levels of miR-3687 and miR-301a-3p while upregulating miR-3612 in TGF-ß-induced HT-29 cells. In conclusion, OXY inhibits human colon cancer cell migration by regulating EMT and miRNAs. Based on these findings, it can be stated that OXY promotes anti-metastatic properties in CRC.
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Antineoplásicos/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Transición Epitelial-Mesenquimal/efectos de los fármacos , Extractos Vegetales/uso terapéutico , Estilbenos/uso terapéutico , Antineoplásicos/farmacología , Movimiento Celular/efectos de los fármacos , Células HCT116 , Células HT29 , Humanos , MicroARNs/metabolismo , Extractos Vegetales/farmacología , Estilbenos/farmacologíaRESUMEN
The intake of common polycyclic aromatic hydrocarbons (PAHs), such as benzo[a]pyrene (BaP), is strongly correlated to the initiation of colon cancer. BaP is a well-known pro-carcinogen that is metabolically activated by xenobiotic-metabolizing enzymes. Studies indicate that polymethoxyflavones, including 5-demethylnobiletin (5-DMNB), exhibit anti-inflammatory and anti-carcinogenic properties. However, the effects of 5-DMNB on xenobiotic-metabolizing enzymes and BaP-induced carcinogenesis remain unclear. The combination of BaP and a promoting agent-dextran sulfate sodium (DSS)-has been demonstrated to induce tumors in mouse models. Thus, this study aimed to determine the protective effect of 5-DMNB on carcinogen biotransformation and BaP/DSS-induced colon carcinogenesis. Our results showed that 5-DMNB had a substantial inhibitory effect on CYP1B1 induced by BaP and upregulated the detoxification enzymes UDP-glucuronosyltransferases (UGTs) and glutathione S-transferases (GSTs). Furthermore, subsequent analyses confirmed that the dietary administration of 5-DMNB markedly ameliorated tumor formation in BaP/DSS-treated mice. Exposure to BaP/DSS also significantly elevated TNF-α levels, and the administration of 5-DMNB reversed this increase. Taken together, we determined that 5-DMNB attenuates BaP/DSS-induced colon cancer through the regulation of inflammation and xenobiotic-metabolizing enzymes. These results indicate that 5-DMNB has significant potential as a novel chemopreventive agent for preventing carcinogen activation and inflammation-associated carcinogenesis.
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Antiinflamatorios/uso terapéutico , Anticarcinógenos/uso terapéutico , Carcinogénesis/efectos de los fármacos , Neoplasias del Colon/prevención & control , Flavonas/uso terapéutico , Animales , Benzo(a)pireno , Colon/efectos de los fármacos , Colon/metabolismo , Colon/patología , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Citocromo P-450 CYP1B1/metabolismo , Sulfato de Dextran , Glucuronosiltransferasa/metabolismo , Glutatión Transferasa/metabolismo , Células Hep G2 , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Endogámicos ICRRESUMEN
Lactobacillus spp., a common probiotic used as a dietary supplement, is good for the digestive system. However, its anti-cancer activity still remains unclear. In this study, we aim to examine the effect of Lactobacillus fermentum, Lactobacillus acidophilus and Lactobacillus rhamnosus on azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated cancer. Male ICR mice were injected with 10 mg/kg AOM and 2.5% DSS via drinking water, and then fed with different Lactobacillus (1 × 108 CFU/day) for 14 weeks. The colonic tissues were collected for biomedical analysis, and gut microbiota profiling was detected by next generation high-throughput sequencing comparing to the 16S rRNA gene. We found that pretreatment with Lactobacillus fermentum (Lac.ferm) significantly inhibits colonic tumor formation (P < 0.05) and markedly decreases pro-inflammatory cytokines in AOM/DSS-induced mice. Furthermore, 16S rRNA sequencing data showed that Lac.ferm altered the composition of gut microbiota by reducing the percentage of Bacteroides. Moreover, linear discriminant analysis scores revealed that Lactobacillus fermentum within phylum Firmicutes was the prominent species existing in the Lac.ferm-treated group. Overall, the above findings suggest that dietary Lac.ferm could modulate the gut microbial community, which might be beneficial to alleviating colon cancer progression.
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5-Demethyltangeretin (5-DTAN), a polymethoxylated flavone found in citrus peels, exhibits highly potent anti-cancer activity. However, 5-DTAN is a hydrophobic compound with poor aqueous solubility, which limits its oral bioavailability and efficacy. In this study, we aimed to develop and characterize an optimal self-microemulsifying delivery system (SMEDS) formulated for 5-DTAN and to assess its anticancer activity in a xenograft model. SMEDS is a lipid-based formulation and typically comprises oil, surfactant, and co-surfactant. The results from our solubility and compatibility test revealed that ethyl oleate and d-limonene were appropriate for use as an oil phases. The optimal formulation comprised ethyl oleate/d-limonene (10%/5%), Cremophor® EL (59.5%), and PEG 400 (25.5%). With this optimal formulation, the mean particle size was 97.1 ± 6.50 nm with the highest 5-DTAN loading (3.01 ± 0.38 mg/mL) determined by photon correlation spectroscopy. The transmission electron microscopy (TEM) morphology of 5-DTAN microemulsion droplets demonstrated a spherical shape and uniform size. Our findings suggest that using 5-DTAN loading SMEDS is an effective approach for inhibiting tumor growth in colon cancer xenograft mice. In summary, this study is the first to successfully demonstrate that oral administration of 5-DTAN-loaded SMEDS serves as a promising nutraceutical for cancer prevention.
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Neoplasias del Colon/tratamiento farmacológico , Sistemas de Liberación de Medicamentos , Flavonas/administración & dosificación , Administración Oral , Animales , Antineoplásicos Fitogénicos , Química Farmacéutica , Neoplasias del Colon/patología , Emulsiones , Células HT29 , Humanos , Limoneno/química , Masculino , Ratones , Ácidos Oléicos/química , Tamaño de la Partícula , Tensoactivos/química , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
Obesity has become a global public health issue. Promoting browning of white adipose tissue (WAT) helps to maintain energy homeostasis. Previous studies have found that citrus fruit exhibits a number of biological activities. Although most citrus fruit drop has been considered agricultural waste, the ability to use it may be desirable. In this study, we investigate the antiobesity effects of immature citrus fruits in high-fat diet (HFD)-fed mice. The main phytochemical components of immature Citrus reticulata in water extraction analyzed by HPLC are synephrine, narirutin, hesperidin, nobiletin, and tangeretin (16.0 ± 1.08, 4.52 ± 0.31, 9.14 ± 0.32, 2.54 ± 0.07, 1.67 ± 0.05 mg/g, respectively). Oral administration of 1% immature Citrus reticulata extract (ICRE) for 11 weeks markedly reduced body weight gain, epididymal fat weight, fasting blood glucose, serum triglyceride, and total cholesterol ( P < 0.05 for all). In addition, histological analysis revealed that dietary ICRE decreased adipocyte size and hepatic steatosis compared to the HFD group ( P < 0.05 for both). Furthermore, we found that mice treated with ICRE have improved cold tolerance during acute cold challenge. These effects were associated with increased expression of uncoupling protein 1 (UCP1) and thermogenic genes in inguinal WAT. Taken together, these results suggest that ICRE can prevent obesity and lipid accumulation through induction of brown-like adipocyte formation.
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Adipocitos Beige/efectos de los fármacos , Tejido Adiposo Blanco/efectos de los fármacos , Citrus/química , Obesidad/tratamiento farmacológico , Extractos Vegetales/administración & dosificación , Adipocitos Beige/metabolismo , Tejido Adiposo Blanco/metabolismo , Animales , Glucemia/metabolismo , Peso Corporal/efectos de los fármacos , Citrus/crecimiento & desarrollo , Dieta Alta en Grasa/efectos adversos , Frutas/química , Frutas/crecimiento & desarrollo , Humanos , Insulina/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Obesidad/genética , Obesidad/metabolismo , Obesidad/fisiopatología , Extractos Vegetales/química , Termogénesis/efectos de los fármacos , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismoRESUMEN
SCOPE: Boswellia serrata (BS) resin is a popular dietary supplement for joint nourishment. In this study, we investigated the chemopreventive effects of dietary BS extract and its impact of gut microbiota on azoxymethane/dextran sulfate sodium (AOM/DSS)-induced colitis-associated colon cancer in mice. METHODS AND RESULTS: Male ICR mice were injected with AOM and 2% DSS via drinking water. The mice were fed with 0.25 or 0.5% BS extract, and colonic tissue were collected at 15 weeks. The main effective components of BS supercritical CO2 extraction were analyzed by LC-MS/MS are boswellic acids. We found that treatment with BS extract significantly reduce the colonic tumor formation. Western blot and histological analysis revealed that dietary BS extract could markedly reduce the inflammation associated protein levels expression. Furthermore, BS extract reduced cell proliferation via inhibiting phosphorylation level of protein kinase B (Akt), glycogen synthase kinase 3ß (GSK3ß), and downregulation of cyclin D1. In addition, BS extract also altered the composition of gut microbiota by enhancing the proportion of Clostridiales and reducing the percentage of Bacteroidales. CONCLUSION: In summary, BS extract decreased the protein levels of inflammative enzymes such as inducible nitric oxide synthase and cyclooxygenase-2 in colonic mucosa. It also mediated Akt/GSK3ß/cyclin D1 signaling pathway and altered the composition of gut microbiota to alleviate tumor growth. Taken together, this study suggests that BS extract has great potential to suppress colon tumorigenesis.
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Boswellia , Neoplasias del Colon/tratamiento farmacológico , Extractos Vegetales/farmacología , Resinas de Plantas/farmacología , Animales , Azoximetano , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/patología , Ciclina D1/antagonistas & inhibidores , Sulfato de Dextran , Glucógeno Sintasa Quinasa 3 beta/antagonistas & inhibidores , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos ICR , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidoresRESUMEN
Choledochal cysts rarely present with acute pancreatitis. We report a patient with type I choledochal cyst(s) who had concomitant acute frank hemorrhagic pancreatitis. A 14-year-old male noted with a history of recurrent abdominal pain, fever and jaundice. Ultrasonography (US) of abdomen at the Emergency Department depicted distended gall bladder with wall thickening. Apparently dilated intrahepatic ducts (IHDs) and fusiform dilatation of the common bile duct (CBD), and mild dilatation of the pancreatic duct were also noted, suggesting a type I choledochal cyst( ). Computed tomography (CT) demonstrated calcifications in the uncinate process of the pancreas in addition to the similar findings on US. He subsequently underwent choledochal cyst excision with a Roux-en-Y hepaticojejunostomy. After surgical treatment, he has been doing well for 3 years.