RESUMEN

There is significant interest in using postbiotics as an intervention strategy to address obesity. This study assesses the efficacy of postbiotics derived from different sourdough strains (Lactiplantibacillus plantarum LP1, LP25, and Pediococcus pentosaceus PP18) in mitigating intestinal injury in zebrafish fed on a high-fat diet. We screened postbiotics for their anti-colon cancer cell effects and compared various preparation methods applied to live bacterial strains, including heat-killing at different temperatures, pH adjustments, and ultraviolet radiation exposure. Heat-killing at 120 °C proved to be the most effective preparation method. A marked variation in health effects was observed in the heat-killed microbial cells, as evidenced by their hydrophobicity and self-aggregation ability. A five-week high-fat dietary intervention study in zebrafish demonstrated that diets supplemented with 108 CFU g-1 K-LP25 significantly attenuated weight gain and body fat, along with reductions in FASN, Leptin, and SREBF1 mRNA expression. However, diets supplemented with 107 CFU g-1 K-PP18 only reduced Leptin and SREBF1 mRNA expression. K-PP18 was more effective at mitigating gut barrier damage, promoting colonic Occludin, ZO-1, and Claudin-1 levels. Additionally, K-LP25 supplementation markedly downregulated the pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß, reducing intestinal inflammation. Supplementation with K-LP1 and K-PP18 increased the abundance of Acinetobacter spp., whereas K-LP25 increased the abundance of Cetobacterium and Plesiomonas. Collectively, these findings suggest that inactivated strains confer protective effects against high-fat diet-induced intestinal damage in zebrafish, with variation observed across different species. Studying the effects of sourdough-derived postbiotics on gut health may open new avenues for dietary interventions to manage gut-related diseases.

Asunto(s)

Dieta Alta en Grasa , Pez Cebra , Animales , Dieta Alta en Grasa/efectos adversos , Humanos , Pan , Pediococcus pentosaceus/metabolismo , Probióticos/farmacología , Intestinos/microbiología , Intestinos/efectos de los fármacos , Masculino , Microbioma Gastrointestinal/efectos de los fármacos

RESUMEN

Hepatocellular carcinoma (HCC) is one of the malignant tumors with high morbidity and mortality. Long non-coding RNAs (lncRNAs) are frequently dysregulated in human cancers and play an important role in the initiation and progression of HCC. Here, we investigated the expression of a new reported lncRNA495810 in our previous study by analyzing the publicly available datasets and using RT-qPCR assay. The cell proliferation experiment, cell cycle and apoptosis assay, wound healing assay, cell migration assay were used to explore the biological function of lncRNA495810 in HCC. The western blot, RNA pull down and RNA immunoprecipitation (RIP) detection were used to investigate the potential molecular mechanisms of lncRNA495810. The results demonstrated that lncRNA495810 was significantly upregulated in hepatocellular carcinoma and associated with poor prognosis of hepatocellular carcinoma patients. Moreover, it proved that lncRNA495810 promotes the proliferation and metastasis of hepatoma cells by directly binding and upregulating the expression of fatty acid-binding protein 5. These results reveal the oncogenic roles of lncRNA495810 in HCC and provide a potential therapeutic target for HCC.

RESUMEN

Diabetes is one of the major global public health problems. Our previous results found that oat ß-D-glucan exhibited ameliorative effects on diabetic mice, but the underlying mechanism is unclear. The present study indicates that oat ß-D-glucan increased glycogen content, decreased glycogen synthase (GS) phosphorylation and increased hepatic glycogen synthase kinase 3ß (GSK3ß) phosphorylation for glycogen synthesis via PI3K/AKT/GSK3-mediated GS activation. Moreover, oat ß-D-glucan inhibited gluconeogenesis through the PI3K/AKT/Foxo1-mediated phosphoenolpyruvate carboxykinase (PEPCK) decrease. In addition, oat ß-D-glucan enhanced glucose catabolism through elevated protein levels of COQ9, UQCRC2, COXIV and ATP5F complexes involved in oxidative phosphorylation, as well as that of TFAM, a key regulator of mitochondrial gene expression. Importantly, our results showed that oat ß-D-glucan maintained hepatic glucose balance via TLR4-mediated intracellular signal. After TLR4 blocking with anti-TLR4 antibody, oat ß-D-glucan had almost no effect on high glucose-induced HepG2 cells. These data revealed that oat ß-D-glucan maintains glucose balance by regulating the TLR4/PI3K/AKT signal pathway.

Asunto(s)

Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Resistencia a la Insulina , Ratones , Animales , Diabetes Mellitus Tipo 2/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Avena , Receptor Toll-Like 4 , Glucanos , Glucógeno Sintasa Quinasa 3 , Glucosa/metabolismo , Glucógeno/metabolismo , Glucógeno Sintasa Quinasa 3 beta

RESUMEN

Diabetes is the most common metabolic disorder, with an extremely serious effect on health systems worldwide. It has become a severe, chronic, non-communicable disease after cardio-cerebrovascular diseases. Currently, 90% of diabetic patients suffer from type 2 diabetes. Hyperglycemia is the main hallmark of diabetes. The function of pancreatic cells gradually declines before the onset of clinical hyperglycemia. Understanding the molecular processes involved in the development of diabetes can provide clinical care with much-needed updates. This review provides the current global state of diabetes, the mechanisms involved in glucose homeostasis and diabetic insulin resistance, and the long-chain non-coding RNA (lncRNA) associated with diabetes.

Asunto(s)

Diabetes Mellitus Tipo 2 , Hiperglucemia , Resistencia a la Insulina , ARN Largo no Codificante , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo

RESUMEN

Aberrant expression of long non­coding RNA (lncRNA) plays an important role in malignant progression of colon cancer and has become a new therapeutic target. In the present study, it was found that the expression of a novel lncRNA 495810 was significantly upregulated in colon cancer and correlated with poor prognosis in patients with colorectal cancer. The highly expressed lncRNA 495810 promoted the proliferation and inhibited apoptosis of CRC cells. Furthermore, the results of gene enrichment analysis indicated that 495810­targeted genes were enriched in the glycolysis pathway and overexpression of 495810 enhanced aerobic glycolysis in colon cancer cells. More importantly, the expression of lncRNA 495810 was positively correlated with the glycolytic rate­limiting enzyme pyruvate kinase isozyme M2 (PKM2). Notably, the data suggested that lncRNA 495810 physically interacted with PKM2 protein and enhanced PKM2 protein stability via the ubiquitin­proteasome pathway. The present findings suggested that lncRNA 495810, a glycolysis­related oncogenic lncRNA, is a potential biomarker for predicting prognosis and a therapeutic target for colon cancer.

Asunto(s)

Neoplasias del Colon , Neoplasias Colorrectales , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Piruvato Quinasa/genética , Piruvato Quinasa/metabolismo , Isoenzimas/genética , Isoenzimas/metabolismo , Proliferación Celular/genética , Neoplasias Colorrectales/patología , Neoplasias del Colon/genética , Glucólisis/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica

RESUMEN

AIM: The aim of this study was to examine the effect of an online multidisciplinary weight loss management programme. METHODS: Between July 2016 and July 2017 this randomized controlled trial recruited patients in Nanjing, China who were living with type 2 diabetes mellitus and who were obese or overweight and randomized them to online versus conventional groups. All participants were managed by a multidisciplinary team. The experimental group was managed using the Why Wait WeChat Platform for Weight Reduction Management. RESULTS: There were 55 and 52 participants in the online and conventional groups, respectively. The decreases in fasting blood glucose (-4.26 vs. -2.99 mmol/L), 2-h postprandial blood glucose (-4.48 vs. -2.68 mmol/L) and glycated haemoglobin (-22.11 vs. -6.21 mmol/mol) were more pronounced in the online compared to conventional group (all P < 0.05). After the intervention, self-management ability parameters, including diet control, foot care and total score, were improved in the online group compared with the conventional group, as well as all indexes of quality of life (all P < 0.05). CONCLUSION: The online multidisciplinary weight loss management programme improved blood glucose in obese or overweight patients living with type 2 diabetes mellitus. Self-management ability parameters (including diet control, foot care and total score) and quality of life were improved in the online group compared with the conventional group.

Asunto(s)

Diabetes Mellitus Tipo 2 , Programas de Reducción de Peso , Humanos , Diabetes Mellitus Tipo 2/terapia , Glucemia , Sobrepeso , Calidad de Vida , Obesidad/terapia , Pérdida de Peso

RESUMEN

Oats are widely distributed worldwide and oat ß-glucan has positive effects on human health. Particularly, oat ß-glucan is reported to be beneficial in the management of type 2 diabetes. The aim of the present study is to investigate the effects of oat ß-glucan and its possible underlying mechanisms on diabetes in type 2 diabetic mice that was induced by streptozotocin/high-fat diet (STZ/HFD). The data indicated that oat ß-glucan significantly reduced the fasting blood glucose, improved glucose tolerance, and insulin sensitivity. The results further showed that oat ß-glucan remarkably decreased the levels of total cholesterol (TCHO), total triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and free fatty acids. Moreover, oat ß-glucan remarkably increased the hepatic glycogen content, but largely decreased the levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in STZ/HFD-induced diabetic mice. Histological analysis showed that oat ß-glucan alleviated visceral lesions. Finally, the metabolomic analysis indicated that the metabolic profile was remarkably changed after oat ß-glucan intervention in diabetic mice. There were 88 and 106 differential metabolites screened as biomarkers in negative ion mode (NEG) and positive ion mode (POS) after oat ß-glucan treatment, respectively. In addition, oat ß-glucan significantly affected the serum metabolites of amino acids, organic acids and bile acids. Collectively, the current study elucidates oat ß-glucan displays an effective nutritional intervention in diabetes.

Asunto(s)

Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Humanos , Ratones , Animales , Dieta Alta en Grasa/efectos adversos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Estreptozocina , Diabetes Mellitus Experimental/tratamiento farmacológico , LDL-Colesterol , Glucemia/metabolismo , Avena/química , Avena/metabolismo

RESUMEN

Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease and has become a growing public health concern worldwide. Polyphenols may improve high-fat diet (HFD)-related NAFLD. Our previous study found that ferulic acid (FA) and p-coumaric acid (p-CA) were the polyphenols with the highest content in foxtail millet. In this study, we investigated the mechanism underlying the impact of ferulic acid and p-coumaric acid (FA/p-CA) on non-alcoholic fatty liver (NAFLD). The association of FA and p-CA with fatty liver was first analyzed by network pharmacology. Synergistic ameliorating of NAFLD by FA and p-CA was verified in oleic acid (OA) and palmitic acid (PA) (FFA)-treated hepatocytes. Meanwhile, FA/p-CA suppressed final body weight and TG content and improved liver dysfunction in HFD-induced NAFLD mice. Mechanistically, our data indicated that FA and p-CA bind to histone deacetylase 1 (HDAC1) to inhibit its expression. The results showed that peroxisome proliferator activated receptor gamma (PPARG), which is positively related to HDAC1, was inhibited by FA/p-CA, and further suppressed fatty acid binding protein (FABP) and fatty acid translocase (CD36). It suggests that FA/p-CA ameliorate NAFLD by inhibiting free fatty acid uptake via the HDAC1/PPARG axis, which may provide potential dietary supplements and drugs for prevention of NAFLD.

Asunto(s)

Enfermedad del Hígado Graso no Alcohólico , Animales , Ratones , Antígenos CD36/metabolismo , Dieta Alta en Grasa , Ácidos Grasos no Esterificados/metabolismo , Histona Desacetilasa 1/metabolismo , Metabolismo de los Lípidos , Hígado/metabolismo , Ratones Endogámicos C57BL , Enfermedad del Hígado Graso no Alcohólico/tratamiento farmacológico , Enfermedad del Hígado Graso no Alcohólico/etiología , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Polifenoles/uso terapéutico , PPAR gamma/metabolismo

RESUMEN

Diarrhea-predominant irritable bowel syndrome (IBS-D) is common among the captive South China tigers in zoos. 16S rRNA gene sequencing was performed to demonstrate the compositions and structures of the gastrointestinal microbiota of this species with IBS-D. Their healthy (F1) and mushy (F2) feces were allocated into two groups. A total of 21 and 31 fecal bacterial communities of major phyla and genera were detected, respectively. The F1 and F2 groups had five common microbiotas at the phylum level (Firmicutes, Proteobacteria, Fusobacteria, Actinobacteria, and Bacteroidetes). Among the five phyla, the abundance of Bacteroidetes in the F2 group was significantly lower than that in the F1 group. The diversity level of fecal microbiota within the mild-diarrhea stool was also significantly lower than that of the healthy counterpart. Thirty-two metabolites were correlated to four genus-level bacteria (Bacteroides, Pseudoclavibacter, Streptococcus, and Ruminococcaceae-UCG-005). Due to its normal role in protein degradation and metabolism, we hypothesized that the lower abundance of Bacteroides within the F2 group could be associated with the IBS-D symptoms. Therefore, this work implied that ameliorating the daily diet with a supplement of probiotics, such as Bacteroides, could improve the gut health of this species.

Asunto(s)

Microbioma Gastrointestinal , Síndrome del Colon Irritable , Tigres , Animales , Síndrome del Colon Irritable/microbiología , Tigres/genética , Tigres/microbiología , ARN Ribosómico 16S/genética , Heces/microbiología , Diarrea/veterinaria , Bacterias/genética , Metabolómica , Bacteroidetes/genética , China

RESUMEN

Polyphenol-rich foods are gaining popularity due to their potential beneficial effects in the prevention and treatment of cancer. Foxtail millet is one of the important functional foods, riches in a variety of biologically active substance. Our previous study showed that ferulic acid (FA) and p-coumaric acid (p-CA) are the main anticancer components of foxtail millet bran, and the two have a significant synergistic effect. In the present study, the clinical application potential of FA and p-CA (FA + p-CA) were evaluated in vivo and in vitro. The FA and p-CA target gene enrichment analysis discovered that FA + p-CA were associated with aerobic glycolysis. It was further shown that FA + p-CA remodel aerobic glycolysis by inhibiting the glycolysis-associated lncRNA 495810 and the glycolytic rate-limiting enzyme M2 type pyruvate kinase (PKM2). Moreover, PKM2 expression was positively correlated with lncRNA 495810. More interestingly, the exogenous expression of lncRNA 495810 eliminated the inhibitory effects of FA + p-CA on aerobic glycolysis. Collectively, FA + p-CA obstruct the aerobic glycolysis of colorectal cancer cells via the lncRNA 495810/PKM2 axis, which provides a nutrition intervention and treatment candidate for colorectal cancer.

Asunto(s)

Neoplasias Colorrectales , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Piruvato Quinasa/metabolismo , Polifenoles , Línea Celular Tumoral , Glucólisis , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética

RESUMEN

Introduction: Heavy metals were classified as essential, probably essential, and potentially toxic in the general population. Until now, it has been reported inconsistently on the association between heavy metals and BC. In this meta-analysis, we aimed to assess the association between heavy metals and BC and review the potential mechanisms systematically. Methods: We searched for epidemiological studies in English about the association between heavy metals and BC published before September 2020 in PubMed, Web of Science, and Embase databases. In total 36 studies, comprising 4,151 individuals from five continents around the world were identified and included. Results: In all biological specimens, Cu, Cd, and Pb concentrations were higher, but Zn and Mn concentrations were lower in patients with BC than in non-BC participants [SMD (95% CIs): 0.62 (0.12, 1.12); 1.64 (0.76, 2.52); 2.03 (0.11, 3.95); -1.40 (-1.96, -0.85); -2.26 (-3.39, -1.13); p = 0.01, 0.0003, 0.04, <0.0001, <0.0001]. Specifically, higher plasma or serum Cu and Cd, as well as lower Zn and Mn, were found in cases [SMD (95% CIs): 0.98 (0.36, 1.60); 2.55 (1.16, 3.94); -1.53 (-2.28, -0.78); -2.40 (-3.69, -1.10); p = 0.002, 0.0003, <0.0001, 0.0003]; in hair, only lower Zn was observed [SMD (95% CIs): -2.12 (-3.55, -0.68); p = 0.0004]. Furthermore, the status of trace elements probably needs to be re-explored, particularly in BC. More prospective studies, randomized clinical trials, and specific pathogenic studies are needed to prevent BC. The main mechanisms underlying above-mentioned findings are comprehensively reviewed. Conclusion: For BC, this review identified the current knowledge gaps which we currently have in understanding the impact of different heavy metals on BC. Systematic Review Registration: www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020176934, identifier: CRD42020176934.

RESUMEN

Resistance to 5-Fluorouracil (5-Fu) chemotherapy is the main cause of treatment failure in the cure of colon cancer. Therefore, there is an urgent need to explore a safe and effective multidrug resistance reversal agent for colorectal cancer, which would be of great significance for improving clinical efficacy. The dietary flavonoid kaempferol plays a key role in the progression of colorectal cancer and 5-Fu resistance. However, the molecular mechanism of kaempferol in reversing 5-Fu resistance in human colorectal cancer cells is still unclear. We found that kaempferol could reverse the drug resistance of HCT8-R cells to 5-Fu, suggesting that kaempferol alone or in combination with 5-Fu has the potential to treat colorectal cancer. It is well known that aerobic glycolysis is related to tumor growth and chemotherapy resistance. Indeed, kaempferol treatment significantly reduced glucose uptake and lactic acid production in drug-resistant colorectal cancer cells. In terms of mechanism, kaempferol promotes the expression of microRNA-326 (miR-326) in colon cancer cells, and miR-326 could inhibit the process of glycolysis by directly targeting pyruvate kinase M2 isoform (PKM2) 3'-UTR (untranslated region) to inhibit the expression of PKM2 or indirectly block the alternative splicing factors of PKM mRNA, and then reverse the resistance of colorectal cancer cells to 5-Fu. Taken together, our data suggest that kaempferol may play an important role in overcoming resistance to 5-Fu therapy by regulating the miR-326-hnRNPA1/A2/PTBP1-PKM2 axis.

Asunto(s)

Neoplasias del Colon , Neoplasias Colorrectales , MicroARNs , Proteínas Portadoras , Línea Celular Tumoral , Neoplasias del Colon/genética , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Resistencia a Antineoplásicos/genética , Fluorouracilo/farmacología , Fluorouracilo/uso terapéutico , Regulación Neoplásica de la Expresión Génica , Glucólisis , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Humanos , Quempferoles , Proteínas de la Membrana , MicroARNs/metabolismo , Proteína de Unión al Tracto de Polipirimidina/metabolismo , Hormonas Tiroideas , Proteínas de Unión a Hormona Tiroide

RESUMEN

Whole grain cereals have been the basis of human diet since ancient times. Due to rich in a variety of unique bioactive ingredients, they play an important role in human health. This review highlights the contents and distribution of primary functional components and their health effects in commonly consumed whole grain cereals, especially dietary fiber, protein, polyphenols, and alkaloids. In general, cereals exert positive effects in the following ways: 1) Restoring intestinal flora diversity and increasing intestinal short-chain fatty acids. 2) Regulating plasma glucose and lipid metabolism, thereby the improvement of obesity, cardiovascular and cerebrovascular diseases, diabetes, and other chronic metabolic diseases. 3) Exhibiting antioxidant activity by scavenging free radicals. 4) Preventing gastrointestinal cancer via the regulation of classical signaling pathways. In summary, this review provides a scientific basis for the formulation of whole-grain cereals-related dietary guidelines, and guides people to form scientific dietary habits, so as to promote the development and utilization of whole-grain cereals.

Asunto(s)

Grano Comestible , Granos Enteros , Humanos , Fibras de la Dieta , Dieta , Obesidad/prevención & control

RESUMEN

BACKGROUND: Nostoc commune Vauch. is a nitrogen-fixing blue-green algae that expresses a large number of active molecules with medicinal properties. Our previous study found that a water stress protein (WSP1) from N. commune and its recombinant counterpart (Re-WSP1) exhibited significant anti-colon cancer activity both in vitro and in vivo. This study is to investigate the effects of Re-WSP1 on proliferation of colon cancer cells and to elucidate the relevant mechanisms. METHODS: Real-time quantitative PCR was used to detect the expression of miR-539 in colon cancer HT-29 and DLD1 cells. Colon cancer cells were transfected with miR-539 mimics and negative controls, and cell proliferation were detected by CCK8 and clonogenic assays. The target gene of miR-539 was predicted, and the dual luciferase reporter gene experiment was used to verify the target gene. After colon cancer cells were transfected with miR-539 mimics or inhibitors, the expression of target gene ß-catenin was detected by Western blot. miR-539 inhibitor confirmed cell proliferation. RESULTS: Re-WSP1 inhibited colon cancer cell growth in a dose-dependent manner. Re-WSP1 inhibited the expression of ß-catenin, which was partly reversed by LiCl treatment. Quantitative PCR analysis showed that the expression of miR-539 was significantly upregulated after Re-WSP1 treatment. Moreover, miR-539 negatively regulated the expression of ß-catenin by directly binding to the 3'UTR of ß-catenin mRNA. The cell growth inhibition and the decrease in ß-catenin expression induced by Re-WSP1 were significantly reversed by miR-539 inhibitor. CONCLUSION: Re-WSP1 suppresses colon cancer cell growth via the miR-539/ß-catenin axis.

Asunto(s)

Proteínas Bacterianas/farmacología , Neoplasias del Colon/metabolismo , MicroARNs/metabolismo , Proteínas de Neoplasias/metabolismo , Nostoc commune/genética , ARN Neoplásico/metabolismo , Transducción de Señal/efectos de los fármacos , beta Catenina/metabolismo , Proteínas Bacterianas/genética , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Células HT29 , Humanos , MicroARNs/genética , Proteínas de Neoplasias/genética , ARN Neoplásico/genética , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacología , beta Catenina/genética

RESUMEN

The WNT signaling pathway plays a crucial role in oviduct/fallopian development. However, the specific physiological processes regulated by the WNT pathway in the fallopian/oviduct function remain obscure. Benefiting from the Lgr4 knockout mouse model, we report the regulation of oviduct epithelial secretion by LGR4. Specifically, the loss of Lgr4 altered the mouse oviduct size and weight, severely reduced the number of oviductal epithelial cells, and ultimately impaired the epithelial secretion. These alterations were mediated by a failure of CTNNB1 protein accumulation in the oviductal epithelial cytoplasm, by the modulation of WNT pathways, and subsequently by a profound change of the gene expression profile of epithelial cells. In addition, selective activation of the WNT pathway triggered the expression of steroidogenic genes, like Cyp11a1 and 3ß-Hsd1, through the activation of the transcriptional factor NR5A2 in an oviduct primary cell culture system. As demonstrated, the LGR4 protein modulates a WNT-NR5A2 signaling cascade facilitating epithelial secretory cell maturation and steroidogenesis to safeguard oviduct development and function in mice.

RESUMEN

Colon cancer is an aggressive malignancy with very limited therapeutic approaches. The available therapeutic agents for colon cancer show strong adverse effects and poor effectiveness, indicating the urgent need to identify new therapeutic drugs for this malignancy. Kaempferol, a flavonoid found in a variety of natural foods, exhibits significant inhibitory effects on colon cancer. Here, it was found that kaempferol inhibited the proliferation of human colon cancer cells HCT116 and DLD1 in a dose-dependent manner, and the IC50 values were 63.0 ± 12.9 and 98.3 ± 15.9 µM, respectively. Also, kaempferol treatment delayed G1 phase progression of cell cycle and induced apoptosis. Aerobic glycolysis is the major energy source for various tumor growths, including colon cancer. Indeed, kaempferol treatment impaired glucose consumption, which subsequently led to reduced lactic acid accumulation and ATP production. Mechanistically, kaempferol promoted the expression of miR-339-5p. Further studies identified hnRNPA1 and PTBP1 as two direct targets of miR-339-5p. By directly targeting hnRNPA1 and PTBP1, miR-339-5p reduced the expression of M2-type pyruvate kinase (PKM2) but induced that of PKM1. In conclusion, these data demonstrate that by modulating miR-339-5p-hnRNPA1/PTBP1-PKM2 axis, kaempferol inhibits glycolysis and colon cancer growth, which reveals a new explanation for the molecular mechanism underlying kaempferol anti-tumor.

Asunto(s)

Neoplasias del Colon , MicroARNs , Empalme Alternativo , Línea Celular Tumoral , Proliferación Celular , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/genética , Glucólisis , Ribonucleoproteínas Nucleares Heterogéneas/metabolismo , Humanos , Quempferoles/farmacología , MicroARNs/genética , MicroARNs/metabolismo , Proteína de Unión al Tracto de Polipirimidina/metabolismo

RESUMEN

Lolium perenne L. and Sorghum sudanense (Piper) Stapf. are 2 common forages fed to blue sheep (Pseudois nayaur Hodgson, 1833) in captivity. However, the effect of these 2 forages on the gastrointestinal microbiota is largely unknown. We analyzed the diversity of the microbiota in the feces of captive blue sheep fed with L. perenne (group F1) and S. sudanense (group F2) by 16S rRNA sequencing. A total of 20 major phyla and 29 genera fecal bacterial communities were detected in the 2 groups. The F1 and F2 groups shared common microbiota at the phylum level, which mainly consisted of Firmicutes and Bacteroidetes. Ruminococcaceae_UCG-005, Eubacterium_coprostanoligenes_group, Ruminococcaceae_UCG-013, and Ruminococcaceae_UCG-010 were the top 4 dominant taxa at the genus level. The percentage of Ruminococcaceae_UCG-010 was significantly higher in the F2 group (∼2.75-fold) than in F1 group. The diversity and abundance of the microbial community in F2 was higher than that in F1. Although both of L. perenne and S. sudanense affect the metabolism of the gastrointestinal microbiota of blue sheep, the S. sudanense improves more aspects of metabolism and biogenesis. In summary, our results demonstrated that L. perenne and S. sudanense affect blue sheep gastrointestinal microbiota in different ways. But S. sudanense efficiently improved the gastrointestinal microbiota of blue sheep.

Asunto(s)

Alimentación Animal , Bacterias/clasificación , Heces/microbiología , Microbioma Gastrointestinal , Ovinos/microbiología , Animales , Bacterias/genética , Bacterias/aislamiento & purificación , Biodiversidad , ADN Bacteriano , Secuenciación de Nucleótidos de Alto Rendimiento , Lolium , Filogenia , ARN Ribosómico 16S/genética , Ovinos/metabolismo , Sorghum

RESUMEN

Lithothamnion sp., a red algae of the Corallinaceae family, when harvested in its calcareous form, is rich in calcium, magnesium and a variety of trace minerals. It is used as a beneficial dietary mineral supplement across the world (Aquamin F). This study was designed to evaluate the acute and sub-chronic toxicity of Lithothamnion sp. according to the Procedure and Methods of Food Safety Toxicological Assessment GB-15193 (China). In an acute toxicity test, mice (n = 20, 10 male, 10 female) were administered a single dose of 10 g/kg BW of Lithothamnion sp. No mortality, or signs of toxicity were observed. In the sub-chronic toxicity arm of the study, SD rats (n = 80, 40 male, 40 female) were randomly divided into four groups with 10 rats in each group and provided pelleted food containing the algae at either 0.00 %, 0.625 %, 1.25 %, 2.50 % inclusion rates for 90 days. Lithothamnion sp. at all inclusion rates did not cause any mortality, and no treatment-related changes were observed in body weight, organ weight, feed consumption, feed utilization rate, urinalysis, hematological and biochemical blood analysis, gross necropsy or histopathologic examinations. In summary, the median lethal dose (LD50) of Lithothamnion sp. was >10 g/kg BW. The no-observed-adverse-effect-level (NOAEL) for female and male rats of Lithothamnion sp. under these experimental conditions was 2.69 g/kg BW and 2.10 g/kg BW respectively.

RESUMEN

5'-hydroxymethylcytosine (5hmC), an important 5'-cytosine modification, is altered highly in order in male meiotic prophase. However, the regulatory mechanism of this dynamic change and the function of 5hmC in meiosis remain largely unknown. Using a knockout mouse model, we showed that UHRF1 regulated male meiosis. UHRF1 deficiency led to failure of meiosis and male infertility. Mechanistically, the deficiency of UHRF1 altered significantly the meiotic gene profile of spermatocytes. Uhrf1 knockout induced an increase of the global 5hmC level. The enrichment of hyper-5hmC at transcriptional start sites (TSSs) was highly associated with gene downregulation. In addition, the elevated level of the TET1 enzyme might have contributed to the higher 5hmC level in the Uhrf1 knockout spermatocytes. Finally, we reported Uhrf1, a key gene in male meiosis, repressed hyper-5hmC by downregulating TET1. Furthermore, UHRF1 facilitated RNA polymerase II (RNA-pol2) loading to promote gene transcription. Thus our study demonstrated a potential regulatory mechanism of 5hmC dynamic change and its involvement in epigenetic regulation in male meiosis.

Asunto(s)

5-Metilcitosina/análogos & derivados , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Infertilidad Masculina/enzimología , Profase Meiótica I , Espermatocitos/enzimología , Testículo/enzimología , Ubiquitina-Proteína Ligasas/metabolismo , 5-Metilcitosina/metabolismo , Animales , Proteínas Potenciadoras de Unión a CCAAT/deficiencia , Proteínas Potenciadoras de Unión a CCAAT/genética , Línea Celular , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Regulación hacia Abajo , Epigénesis Genética , Fertilidad , Infertilidad Masculina/genética , Infertilidad Masculina/fisiopatología , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Proto-Oncogénicas/genética , Proteínas Proto-Oncogénicas/metabolismo , ARN Polimerasa II/metabolismo , Transducción de Señal , Espermatocitos/patología , Espermatogénesis , Testículo/patología , Testículo/fisiopatología , Activación Transcripcional , Ubiquitina-Proteína Ligasas/deficiencia , Ubiquitina-Proteína Ligasas/genética