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The study was conducted to determine the proportion and concentration of enterohemorrhagic Escherichia coli (EHEC) O157 and six non-O157 (O26, O45, O103, O111, O121, and O145) serogroups and identify seasonal and processing plant differences in feces and on hides of cull dairy cattle processed in commercial slaughterhouses in the United States. Approximately 60 rectal and 60 hide-on samples from matched carcasses were collected in each of three processing plants, in two periods; summer of 2017 and spring of 2018. Samples before enrichment were spiral plated to quantify EHEC, and postenriched samples underwent culture methods that included immuno-magnetic separation, plating on selective media, and PCR assays for identification and serogroup confirmation of putative isolates. An isolate was considered EHEC O157 positive if it harbored serogroup-specific (rfbE), Shiga toxin (stx1 and/or stx2), and intimin (eae) genes and EHEC non-O157 positive if at least one of the non-O157 serogroup-specific, stx1 and/or stx2, and eae genes was identified. Generalized linear mixed models were fitted to estimate overall proportion of positives for EHEC O157 and non-O157 EHEC serogroups, as well as seasonal and processing plant differences in fecal and hide-on proportion of positives. The fecal EHEC proportion at the sample level was 1.8% (95% CI = 0.0-92.2%) and 4.2% (95% CI = 0.0-100.0%) for EHEC O157 and EHEC non-O157, respectively. Hide sample level proportion of positives was 3.0% (95% CI = 0.0-99.9%) for EHEC O157 and 1.6% (95% CI = 0.0-100.0%) for EHEC non-O157. The proportion of EHEC O157 and non-O157 significantly differed by processing plant and sample type (hide vs. feces), but not by season. The association between proportion of EHEC serogroups in feces with the proportion on hides collected from matched cattle was 7.8% (95% CI = 0.6-53.3%) and 3.8% (95% CI = 0.3-30.8%) for EHEC O157 and non-O157, respectively. Taken together, our findings provide evidence of a low proportion of EHEC serogroups in the feces and on hides of cull dairy cattle and that their proportion varies across processing plants.
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Sorghum is considered a promising food security crop and remarkable rich source of bioactive components including phenolic acids, flavonoids, and tannins. Sorghum phenolics exhibited numerous protective effects against multiple chronic diseases. However, there is no review of the effects of sorghum phenolics on gastrointestinal (GI) health. Specifically, recent studies have highly suggested that sorghum phenolics can maintain gastrointestinal homeostasis and enhance microbial diversity and richness. Furthermore, sorghum phenolics showed GI anticancer effects in both in vitro and in vivo studies against colorectal and esophageal cancers. Treatment of GI related human cancer cell lines stimulated apoptosis and suppressed proliferation. Sorghum intake and extracts treatments reduced intestinal oxidative stress and inflammatory mediators in human and in vivo studies. In addition, understanding the role and mechanisms underlying gastrointestinal health benefits of sorghum phenolics is crucial to determine treatment strategies of different GI diseases.
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BACKGROUND: Exposure to environmental chemicals has been linked with endothelial dysfunction, which is a leading cause of human diseases, including atherosclerosis. Permethrin is a frequently used synthetic pyrethroid insecticide for which longer exposure may cause toxicity in several types of tissues and the development of metabolic diseases, including atherosclerosis, obesity and diabetes. The present study was designed to evaluate the potential adverse effect of permethrin on the function and activity of human endothelial cells. RESULTS: Permethrin was found to repress migration and tube formation by human umbilical vein endothelial cells (HUVECs) in a dose-dependent manner, as well as to significantly repress their viability after 24 and 48 h of treatment. Furthermore, increased reactive oxygen species (ROS) production was observed in cells treated with permethrin, and the permethrin-induced repression of cell viability was ROS-dependent. Permethrin did not influence apoptosis, necrosis or mitochondrial membrane potential in HUVECs. CONCLUSION: The results of the present study suggest that permethrin represses angiogenesis and viability through ROS-dependent and cell growth-, apoptosis- and necrosis-independent means. © 2022 Society of Chemical Industry.
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Aterosclerosis , Permetrina , Apoptosis , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Necrosis , Permetrina/toxicidad , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Colon cancer (CC) is considered a high-risk cancer in developed countries. Its etiology is correlated with a high consumption of red meat and low consumption of plant-based foods, including whole grains. Sorghum bran is rich in polyphenols. This study aimed to determine whether different high-phenolic sorghum brans suppress tumor formation in a genetic CC rodent model and elucidate mechanisms. Tissue culture experiments used colorectal cancer cell lines SW480, HCT-116 and Caco-2 and measured protein expression, and protein activity. The animal model used in this study was APC Min+/mouse model combined with dextram sodium sulfate. High phenolic sorghum bran extract treatment resulted in the inhibition of proliferation and induced apoptosis in CC cell lines. Treatment with high phenolic sorghum bran extracts repressed TNF-α-stimulated NF-κB transactivation and IGF-1-stimulated PI3K/AKT pathway via the downregulation of ß-catenin transactivation. Furthermore, high-phenolic sorghum bran extracts activated AMPK and autophagy. Feeding with high-phenolic sorghum bran for 6 weeks significantly suppressed tumor formation in an APC Min/+ dextran sodium sulfate promoted CC mouse model. Our data demonstrates the potential application of high-phenolic sorghum bran as a functional food for the prevention of CC.
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Proteína de la Poliposis Adenomatosa del Colon/fisiología , Neoplasias Colorrectales/tratamiento farmacológico , Sulfato de Dextran/toxicidad , Modelos Animales de Enfermedad , Extractos Vegetales/farmacología , Sorghum/química , Animales , Apoptosis , Proliferación Celular , Neoplasias Colorrectales/inducido químicamente , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Femenino , Humanos , Masculino , Ratones , Células Tumorales CultivadasRESUMEN
Sorghum is one of the most widely cultivated crops, and is used in foods, domestic animal feedstuffs, alcohol production, and biofuels. Recently, many research groups have demonstrated that sorghum contains various components that are strongly associated with the prevention of major human chronic diseases such as obesity, diabetes, atherosclerosis, cancer, and inflammation. However, to use sorghum more widely as a food for the potential prevention and treatment of human chronic diseases, more studies will be required to elucidate the biological mechanisms. In this review paper, we highlight multiple findings to propose a mechanistic link between sorghum consumption and reduced risk of chronic diseases. © 2020 Society of Chemical Industry.
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Enfermedad Crónica/prevención & control , Sorghum/metabolismo , Animales , Dietoterapia , Humanos , Sorghum/químicaRESUMEN
Anthracycline-based chemotherapy, such as doxorubicin (Dox), while effective against many solid tumors, is not widely used for head and neck cancers. In this study, we evaluated the efficacy of Dox, and its derivative AD198 in human, canine, and feline oral squamous cell carcinomas cells (OSCC) in vitro. Dox and AD198 had significant an anti-proliferative effect on human, canine, and feline OSCC cells in dose-dependent manner. AD198 inhibited cell proliferation more effectively than Dox in tested OSCC cells. In the human oral squamous cell carcinoma SCC25 cells, Dox and AD198 increased the production of reactive oxygen species and subsequently increased apoptosis through activation of caspase signaling pathway. Dox and AD198 increased activation of AKT, ERK1/2, and p38 MAPK signaling pathways in tested OSCC cells by dose-dependent manner. The efficacy of Dox and AD198 treatments in inhibition of cell proliferation was increased in tested OSCC when combined with PI3K/AKT inhibitor, LY294002 treatment. Inhibition of PI3K/AKT reduced Dox- and AD198-induced activation of ERK1/2 and further increased Dox- and AD198-induced phosphorylation of p38 MAPK in OSCC. Our results suggest that the anthracycline therapies, such as Dox or AD198, can be more effective for treatment of OSCC when combined with inhibitors of the PI3K/AKT pathway. J. Cell. Biochem. 118: 2615-2624, 2017. © 2016 Wiley Periodicals, Inc.
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Carcinoma de Células Escamosas/tratamiento farmacológico , Doxorrubicina/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Neoplasias de la Boca/tratamiento farmacológico , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Carcinoma de Células Escamosas/enzimología , Carcinoma de Células Escamosas/patología , Gatos , Línea Celular Tumoral , Perros , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Neoplasias de la Boca/enzimología , Neoplasias de la Boca/patología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidoresRESUMEN
BACKGROUND: Doxorubicin (Dox) is widely used to treat progressed bladder cancer after transurethral resection. The use of Dox-chemotherapy has been limited due to induced drug resistance and cumulative cardiotoxic effects. N-benzyladriamycin-14-valerate (AD198), a novel derivative of Dox, has a potential to become a more effective treatment than Dox by overcoming drug resistance and cardio-toxicity as shown in the rodent model of lymphoma in vivo. The purpose of this study was to compare the efficacy of Dox and AD198 and explore their mechanisms in inhibition on human bladder cancer cells in vitro. METHODS: We evaluated the effects of Dox and AD198 on cell viability of human transitional cell carcinoma (TCC) cell lines T24 and UMUC3 by MTS assay in vitro. The effects of Dox and AD198 on cell apoptosis were determined by caspase 3/7 assay, generation of reactive oxygen species (ROS), and Western Blotting (WB) analysis. RESULTS: AD198 was more effective than Dox in inhibition of cell viability of T24 and UMUC3 cells in vitro. Both Dox and AD198 significantly increased the generation of ROS and induced apoptosis in caspase-dependent and -independent manner in T24 and UMUC3 cells. AD 198 induced significantly higher production of ROS as compared to Dox in human TCC cells. Dox and AD198 activated the pro-apoptotic p38 MAPK pathway; however, on the other hand also increased phosphorylation of AKT, an anti-apoptotic signaling pathway, in T24 and UMUC3 cells. Combined treatment of PI3K inhibitor (LY294002) with Dox or AD198 inhibited cell viability of T24 and UMUC3 cells more effectively than any of drug treatments alone. CONCLUSIONS: These data suggest that AD198 as novel derivative of Dox, could be a used as effective treatment for bladder cancer. Dox and AD198 induced PI3K/AKT signaling pathway that is a one of the indicators of pro-survival and possible drug-resistance mechanisms of chemotherapies in bladder cancer. Combined therapies of Dox or AD198 with inhibitors of PI3K/AKT signaling pathway might lead to more effective treatment outcome for patients diagnosed with bladder cancer based on our in vitro experiments.
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Doxorrubicina/administración & dosificación , Resistencia a Antineoplásicos/efectos de los fármacos , Inhibidores de las Quinasa Fosfoinosítidos-3 , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Apoptosis/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Doxorrubicina/análogos & derivados , Humanos , Fosforilación , Proteínas Proto-Oncogénicas c-akt/genética , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Non-steroidal anti-inflammatory drugs (NSAIDs) are extensively used over the counter to treat headaches and inflammation as well as clinically to prevent cancer among high-risk groups. The inhibition of cyclooxygenase (COX) activity by NSAIDs plays a role in their anti-tumorigenic properties. NSAIDs also have COX-independent activity which is not fully understood. In this study, we report a novel COX-independent mechanism of sulindac sulfide (SS), which facilitates a previously uncharacterized cleavage of epithelial cell adhesion molecule (EpCAM) protein. EpCAM is a type I transmembrane glycoprotein that has been implemented as an over-expressed oncogene in many cancers including colon, breast, pancreas, and prostate. We found EpCAM to be down-regulated by SS in a manner that is independent of COX activity, transcription regulation, de novo protein synthesis, and proteasomal degradation pathway. Our findings clearly demonstrate that SS drives cleavage of the extracellular portion of EpCAM near the N-terminus. This SS driven cleavage is blocked by a deleting amino acids 55-81 as well as simply mutating arginine residues at positions 80 and 81 to alanine of EpCAM. Proteolysis of EpCAM by SS may provide a novel mechanism by which NSAIDs affect anti-tumorigenesis at the post-translational level.
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Antiinflamatorios no Esteroideos/farmacología , Antígenos de Neoplasias/metabolismo , Moléculas de Adhesión Celular/metabolismo , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Ciclooxigenasa 2/metabolismo , Sulindac/análogos & derivados , Animales , Antígenos de Neoplasias/genética , Apoptosis/efectos de los fármacos , Western Blotting , Moléculas de Adhesión Celular/genética , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/patología , Ciclooxigenasa 2/genética , Molécula de Adhesión Celular Epitelial , Técnica del Anticuerpo Fluorescente , Humanos , Ratones , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Sulindac/farmacología , Células Tumorales CultivadasRESUMEN
Our objectives were to determine whether the feedlot-level use of a direct-fed microbial (DFM; Lactobacillus animalis LA51 and Propionibacterium freudenreichii PF24; Bovamine Defend®, 2 × 109 CFU/g) was associated with fecal prevalence and concentration of E. coli O157:H7, and determine pen- and feedlot-level risk factors associated with fecal E. coli O157:H7 prevalence in cattle pens from commercial feedlot operations. Twenty commercial feedlots in Nebraska, ten that included DFM (DFM) and ten that did not (no-DFM), were sampled during the summer of 2017. In each sampling month, 22 pen-floor fecal samples were collected from three pens in each feedlot. Samples were subjected to cultural and molecular procedures for the detection of E. coli O157:H7 (immunomagnetic separation, plating on selective media, followed by PCR confirmation) and spiral plating for quantification. A total of 1,320 samples from 180 pens of finishing cattle belonging to 20 feedlots, which were sampled three times throughout a 12-week period, were processed and tested. Across all feedlots and sampling months, the mean within-pen prevalence was 13.5% (95% CI = 2.6-47.4%). The association between DFM status and the within-pen prevalence of E. coli O157:H7 depended significantly (p < 0.05) on the sampling month. The second sampling month between late July and mid-August corresponded to the highest within-pen prevalence estimates reported in this study, with no-DFM pens having a higher prevalence than DFM pens. After accounting for the DFM status, and based on multivariable analyses, sampling month, average pen body weight, and weather conditions were significantly associated with the within-pen fecal prevalence of E. coli O157:H7. Collectively, these findings demonstrate that the use of a DFM containing Lactobacillus animalis LA51 and Propionibacterium freudenreichii PF26 in feedlots showed potential in reducing fecal E. coli O157:H7 prevalence in cattle during times when prevalence peaks.
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Alimentación Animal , Escherichia coli O157 , Heces , Animales , Bovinos , Heces/microbiología , Infecciones por Escherichia coli/veterinaria , Infecciones por Escherichia coli/epidemiología , Nebraska , Propionibacterium , Recuento de Colonia Microbiana , Derrame de Bacterias , Lactobacillus/aislamiento & purificación , PrevalenciaRESUMEN
Sorghum (Sorghum bicolor L. Moench), characterized by substantial genetic diversity, encompasses some lines rich in health-promoting polyphenols. Laboratory studies have demonstrated anticancer properties of sorghum phenolics; however, their presence may impact nutritional factors, such as digestible starch. The objective of this study was to determine the effects of pH and high-moisture heating on starch digestibility, phenolic profile, and anticancer activity in sorghum. High Phenolic sorghum flour line SC84 was combined with buffer solutions (pH 3, 4, 5, 7, and 8) and heated for 0, 10, 30, 60, or 120 min. Starch digestibility was assessed using the K-DSTRS kit from Megazyme. Changes in phenolic composition were analyzed using total phenolic content (TPC) and condensed tannin content (CTC) assays coupled with reversed phase high performance liquid chromatography (RP-HPLC) analysis. Anticancer potential against human colorectal cancer cells (HCT116 and SW480) was determined though cell viability assay. Results indicated a significant increase in total starch digestibility of sample after heating. Heating samples for 10 min did not significantly reduce TPC of samples. However, CTC was significantly reduced with heating time, while pH exhibited no significant effect on CTC. The measured 3-deoxyanthocyanidins experienced a significant decrease (p < 0.0001), while certain flavonoids increased significantly (p < 0.05) after heating for 30 min or longer. Notably, the 10 min heating duration minimally affected anticancer activity, whereas longer heat times diminished extract efficacy against human colorectal cancer cells. Alkaline pH levels significantly decreased anticancer activity, regardless of heating time. Importantly, heating sorghum for 10 min improved starch digestibility with minimal compromise to potential health benefits. These findings suggest promising implications for the development of high-phenolic sorghum products, and provide valuable insights to guide forthcoming animal and clinical studies. The demonstrated impact of wet-heating on increased starch digestibility, coupled with the preservation of phenolic content and bioactivity, underscores the potential of incorporating high-phenolic sorghum lines in future functional food formulations.
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Sumac sorghum (Sorghum bicolor L. Moench) bran contains polyphenolic compounds with health-promoting properties. Functional food product development can add economic value to sorghum bran, but acceptability may be limited by bitter taste. An acidified cold-brewed sorghum bran beverage was developed, and simplified sweetened (SB) and unsweetened (UB) versions were analyzed for antioxidant profiles (total phenolic content, phenolic profiling via HPLC, condensed tannins, oxygen radical absorbance capacity, and 2,2-diphenyl-1-picrylhydrazyl radical scavenging) and sensory properties. Beverages contained condensed tannins (average of 0.33 mg catechin equivalents per milliliter) along with other flavonoids and demonstrated in vitro antioxidant capacity (3.32-3.96 mmol Trolox equivalents per milliliter). One hundred fourteen consumers, grouped by 6-n-propylthiouracil (bitterness) taster status, rated acceptability (9-point hedonic scales), bitterness intensity (5-point scale), and purchase intent (PI; yes/no) of model beverages. Although the concept was novel, SB was clearly more acceptable to consumers regardless of preference for sweet versus unsweet tea (as a reference product concept). Mean mouthfeel and flavor liking scores were significantly higher for SB (6.2 and 5.1, respectively) than UB (4.8 and 3.0, respectively). Bitterness was suppressed by the sweetness in SB (mean bitterness intensity of 1.8 vs. 2.6 for UB), although 21% of consumers still found it "too bitter." However, consumers' taster status did not affect beverage acceptability nor bitterness perceptions at present phenolic levels (0.53 gallic acid equivalents per milligram). After a sorghum/antioxidant information message, positive PI increased to 56% for SB, impacting more females than males. Enhanced familiarity and effective product messaging can improve acceptability of acidified cold-brewed sorghum bran beverages as a novel functional food product concept. PRACTICAL APPLICATION: New food applications of cereal bran can provide value in terms of byproduct utilization and delivery of health-promoting ingredients. Sorghum bran beverages demonstrated antioxidant activity, and the sweetened formulation showed decreased bitterness and increased acceptability. Consumers were positively influenced by antioxidant information, although most had not previously consumed sorghum.
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Proantocianidinas , Sorghum , Antioxidantes , Grano Comestible/química , Bebidas/análisis , Fenoles/análisis , Comportamiento del ConsumidorRESUMEN
Pendimethalin is globally registered for control of a wide range of weeds in agriculture and home landscaping. Human exposure to pendimethalin can occur by the oral route through food and other sources. Endothelial function is vital to numerous biological processes, and endothelial dysfunction and poor vascular health is associated with increased atherosclerotic events; however, no study has yet investigated the potential effect of pendimethalin on endothelial function and vasculature formation. The objective of the current study is to investigate if pendimethalin may affect the viability and function of vascular endothelial cells. We observed that pendimethalin significantly repressed viability of human endothelial cells, inducing G1 cell cycle arrest and apoptotic/necrotic cell death. Pendimethalin treatment also activated ER stress and autophagy, leading to loss of mitochondrial membrane potential. In addition, pendimethalin impaired the tube forming and migratory abilities of endothelial cells. This study provides previously unrecognized adverse effects of pendimethalin in vascular endothelial cells, mediated by ER stress-induced mitochondrial dysfunction.
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Compuestos de Anilina , Apoptosis , Compuestos de Anilina/toxicidad , Estrés del Retículo Endoplásmico , Células Endoteliales de la Vena Umbilical Humana , Humanos , Mitocondrias/metabolismoRESUMEN
Obesity is one of the leading public health problems that can result in life-threatening metabolic and chronic diseases such as cardiovascular diseases, diabetes, and cancer. Sorghum (Sorghum bicolor (L.) Moench) is the fifth most important cereal crop in the world and certain genotypes of sorghum have high polyphenol content. PI570481, SC84, and commercially available sumac sorghum are high-polyphenol genotypes that have demonstrated strong anti-cancer activities in previous studies. The objective of this study was to explore a potential anti-obesity use of extracts from sorghum bran in the differentiation of 3T3-L1 preadipocytes and to investigate cellular and molecular responses in differentiated adipocytes to elucidate related mechanisms. None of the four different sorghum bran extracts (PI570481, SC84, Sumac, and white sorghum as a low-polyphenol control) caused cytotoxicity in undifferentiated and differentiated 3T3-L1 cells at doses used in this study. Sorghum bran extracts (PI570481, SC84, and Sumac) reduced intracellular lipid accumulation and expression of adipogenic and lipogenic proteins in a dose-dependent manner in differentiated 3T3-L1 cells. The same polyphenol containing sorghum bran extracts also repressed production of reactive oxygen species (ROS) and MAPK signaling pathways and repressed insulin signaling and glucose uptake in differentiated 3T3-L1 cells. These data propose a potential use of high-phenolic sorghum bran for the prevention of obesity.
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Sorghum , Células 3T3-L1 , Adipocitos/metabolismo , Adipogénesis , Animales , Grano Comestible , Ratones , Obesidad/metabolismo , Fenoles/metabolismo , Fenoles/farmacología , Extractos Vegetales/metabolismo , Extractos Vegetales/farmacología , Polifenoles/metabolismo , Polifenoles/farmacologíaRESUMEN
Grain sorghum (Sorghum bicolor) is a gluten-free cereal grown around the world and is a food staple in semi-arid and subtropical regions. Sorghum is a diverse crop with a range of pericarp colour including white, various shades of red, and black, all of which show health-promoting properties as they are rich sources of antioxidants such as polyphenols, carotenoids, as well as micro- and macro-nutrients. This work examined the grain composition of three sorghum varieties possessing a range of pericarp colours (white, red, and black) grown in the Mediterranean region. To determine the nutritional quality independent of the contributions of phenolics, mineral and fatty acid content and composition were measured. Minor differences in both protein and carbohydrate were observed among varieties, and a higher fibre content was found in both the red and black varieties. A higher amount of total saturated fats was found in the white variety, while the black variety had a lower amount of total unsaturated and polyunsaturated fats than either the white or red varieties. Oleic, linoleic, and palmitic were the primary fatty acids in all three analysed sorghum varieties. Significant differences in mineral content were found among the samples with a greater amount of Mg, K, Al, Mn, Fe, Ni, Zn, Pb and U in both red and black than the white sorghum variety. The results show that sorghum whole grain flour made from grain with varying pericarp colours contains unique nutritional properties.
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Phenolic compounds in some specialty sorghums have been associated with cancer prevention. However, direct evidence and the underlying mechanisms for this are mostly unknown. In this study, phenolics were extracted from 13 selected sorghum accessions with black pericarp while F10000 hybrid with white pericarp was used as a control, and cell growth inhibition was studied in hepatocarcinoma HepG2 and colorectal adenocarcinoma Caco-2 cells. Total phenolic contents of the 13 high phenolic grains, as determined by Folin-Ciocalteu, were 30-64 mg GAE/g DW in the phenolic extracts of various accessions compared with the control F10000 at 2 mg GAE/g DW. Treatment of HepG2 with the extracted phenolics at 0-200 µM GAE up to 72 h resulted in a dose- and time-dependent reduction in cell numbers. The values of IC50 varied from 85 to 221 mg DW/mL while the control of F10000 was 1275 mg DW/mL. The underlying mechanisms were further examined using the highest phenolic content of PI329694 and the lowest IC50 of PI570481, resulting in a non-cytotoxic decrease in cell number that was significantly correlated with increased cell cycle arrest at G2/M and apoptotic cells in both HepG2 and Caco-2 cells. Taken together, these results indicated, for the first time, that inhibition of either HepG2 or Caco-2 cell growth by phenolic extracts from 13 selected sorghum accessions was due to cytostatic and apoptotic but not cytotoxic mechanisms, suggesting some specialty sorghums are a valuable, functional food, providing sustainable phenolics for potential cancer prevention.
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Environmental contamination by microplastics (MPs) is an emerging concern in recent years due to associated adverse impacts of MPs on potential human health problems. Endothelial dysfunction is a condition in which the endothelial layer fails to form normally, and is associated with impaired vascular function. Despite the fact that MPs are known to enter the circulation system through intestinal epithelium, little has been known whether MPs impact the normal function of endothelial cells and the formation of vasculature. In the current study, we investigated the effect of polystyrene microplastics (PS-MPs) on tube formation and cytotoxicity in human umbilical vein endothelial cells (HUVECs). Our study showed that the treatment of HUVECs with PS-MPs significantly decreased cell viability, with intracellular accumulation occurring in a dose- and size-dependent manner. Moreover, significant dose-dependent inhibition of angiogenic tube formation was observed in HUVECs treated with 0.5 µm PS-MPs; this effect was accompanied by suppression of angiogenic signaling pathways and inhibitory activity against wound healing and cell migration. Regarding the mechanism of decreased viability, we observed increased autophagic and necrotic cell death. These results indicate that 6-h exposure of endothelial cells to PS-MPs represses tube-forming capacity, while 48-h exposure leads to autophagy and necrosis-mediated cytotoxicity.
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Supervivencia Celular/efectos de los fármacos , Microplásticos/toxicidad , Neovascularización Fisiológica/efectos de los fármacos , Poliestirenos/toxicidad , Animales , Autofagia/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Células Hep G2 , Células Endoteliales de la Vena Umbilical Humana , Humanos , Ratones , Necrosis/etiología , Transducción de Señal/efectos de los fármacosRESUMEN
Japanese encephalitis virus (JEV) is a zoonotic mosquito-borne pathogen that regularly causes severe neurological disease in humans in Southeast Asia and the Western Pacific region. Pigs are one of the main amplifying hosts of JEV and play a central role in the virus transmission cycle. The objective of this study was to identify in vitro cell systems to investigate early effects of JEV infection including viral replication and host cell death. Here, we demonstrate the susceptibility of several porcine cell lines to the attenuated genotype III JEV strain SA14-14-2. Monolayers of porcine nasal turbinate (PT-K75), kidney (SK-RST), testis (ST), and monocyte-derived macrophage (CΔ2+) cells were infected with SA14-14-2 for up to five days at a multiplicity of infection (MOI) of 0.1. The hamster kidney cell line BHK-21, previously shown to be susceptible to SA14-14-2, was used as a positive control. Culture supernatants and cells were collected between 0 and 120 h post infection (hpi), and monolayers were observed for cytopathic effect (CPE) using brightfield microscopy. The number of infectious virus particles was quantified by plaque assay and cell viability was determined using trypan blue staining. An indirect immunofluorescence assay was used to detect the presence of JEV NS1 antigens in cells infected at 1 MOI. All four porcine cell lines demonstrated susceptibility to SA14-14-2 and produced infectious virus by 12 hpi. Virus titers peaked at 48 hpi in CΔ2+, BHK-21, and SK-RST cells, at 72 hpi in PT-K75, and at 120 hpi in ST cells. CPE was visible in infected CΔ2+ and BHK-21 cells, but not the other three cell lines. The proportion of viable cells, as measured by trypan blue exclusion, declined after 24 hpi in BHK-21 and 48 hpi in CΔ2+ cells, but did not substantially decline in SK-RST, PT-K75 or ST cells. At 48 hpi, JEV NS1 was detected in all infected cell lines by fluorescence microscopy. These findings demonstrate several porcine cell lines which have the potential to serve as useful research tools for investigating JEV infection dynamics and host cell mechanisms in a natural amplifying host species, such as pigs, in vitro.
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Antimicrobial resistance in bacterial pathogens associated with bovine mastitis and human foodborne illnesses from contaminated food and water have an impact on animal and human health. Phenolic compounds have antimicrobial properties and some specialty sorghum grains are high in phenolic compounds, and the grain extract may have the potential as a natural antimicrobial alternative. The study's objective was to determine antimicrobial effects of sorghum phenolic extract on bacterial pathogens that cause bovine mastitis and human foodborne illnesses. Bacterial pathogens tested included Escherichia coli, Salmonella Typhimurium, Campylobacter jejuni, Campylobacter coli, Pseudomonas aeruginosa, Klebsiella pneumoniae, Klebsiella oxytoca, Staphylococcus aureus, and Enterococcus faecalis. Antibacterial activities of sorghum phenolic extracts were determined by agar-well diffusion assay. Sorghum phenolic extract was added to the wells in concentrations of 0, 100, 200, 500, 1000, or 4000 µg/mL. The control wells did not receive phenolic extract. Plates were incubated for 18-24 h, and the diameter of each zone of inhibition was measured. The results indicated that sorghum phenolic extract had inhibitory effects on Staphylococcus aureus, Enterococcus faecalis, Campylobacter jejuni, and Campylobacter coli.
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Patchouli alcohol (PA), a tricyclic sesquiterpene, is a dominant bioactive component in oil extracted from the aerial parts of Pogostemon cablin (patchouli). Diverse beneficial activities have been reported, including anti-influenza virus, anti-depressant, anti-nociceptive, vasorelaxation, lung protection, brain protection, anti-ulcerogenic, anti-colitis, pre-biotic-like, anti-inflammatory, anti-cancer and protective activities against metabolic diseases. However, detailed mechanistic studies are required to explore the possibility of developing PA as a functional food material or promising drug for the prevention and treatment of human diseases. This review highlights multiple molecular targets and working mechanisms by which PA mediates health benefits.
Asunto(s)
Antiinflamatorios/farmacología , Antineoplásicos Fitogénicos/farmacología , Inmunosupresores/farmacología , Sesquiterpenos/farmacología , Antiinflamatorios/química , Antineoplásicos Fitogénicos/química , Humanos , Inmunosupresores/química , Sesquiterpenos/químicaRESUMEN
Human colon cancer is the third leading cause of mortality in the United States and worldwide. Chemoprevention using diet is widely accepted as a promising approach for cancer management. Numerous population studies indicate a negative correlation between the incidence of colon cancer and consumption of whole grains with a high content of bioactive phenolic compounds. In the current study, we evaluated the anticancer properties of a high phenolic sorghum bran extract prepared using 70% ethanol with 5% citric acid solvent at room temperature. A significant dose-dependent suppression of cell proliferation was observed in human colon cancer cells treated with the high phenolic sorghum bran extract. Apoptosis and S phase growth arrest were induced, while cell migration and invasion were inhibited by this treatment; these effects were accompanied by altered expression of apoptosis, cell cycle, and metastasis-regulating genes. We also found that the high phenolic sorghum bran extract stimulated DNA damage in association with induction of extracellular signal-regulated kinase (ERK) and c-Jun-NH2-terminal kinase (JNK) and subsequent expression of activating transcription factor 3 (ATF3). The present study expands our understanding of the potential use of high phenolic sorghum bran to prevent human colon cancer.