L-Glutamine Substantially Improves 5-Fluorouracil-Induced Intestinal Mucositis by Modulating Gut Microbiota and Maintaining the Integrity of the Gut Barrier in Mice.

SCOPE: This study investigates the potential of glutamine to mitigate intestinal mucositis and dysbiosis caused by the chemotherapeutic agent 5-fluorouracil (5-FU). METHODS AND RESULTS: Over twelve days, Institute of Cancer Research (ICR) mice are given low (0.5 mg kg-1) or high (2 mg kg-1) doses of L-Glutamine daily, with 5-FU (50 mg kg-1) administered between days six and nine. Mice receiving only 5-FU exhibited weight loss, diarrhea, abnormal cell growth, and colonic inflammation, correlated with decreased mucin proteins, increased endotoxins, reduced fecal short-chain fatty acids, and altered gut microbiota. Glutamine supplementation counteracted these effects by inhibiting the Toll-like receptor 4/nuclear factor kappa B (TLR4/NF-κB) pathway, modulating nuclear factor erythroid 2-related factor 2/heme oxygenase 1 (Nrf2/HO-1) oxidative stress proteins, and increasing mammalian target of rapamycin (mTOR) levels, thereby enhancing microbial diversity and protecting intestinal mucosa. CONCLUSIONS: These findings underscore glutamine's potential in preventing 5-FU-induced mucositis by modulating gut microbiota and inflammation pathways.

NURECON: A Novel Online System for Determining Nutrition Requirements Based on Microbial Composition.

Dietary habits have been proven to have an impact on the microbial composition and health of the human gut. Over the past decade, researchers have discovered that gut microbiota can use nutrients to produce metabolites that have major implications for human physiology. However, there is no comprehensive system that specifically focuses on identifying nutrient deficiencies based on gut microbiota, making it difficult to interpret and compare gut microbiome data in the literature. This study proposes an analytical platform, NURECON, that can predict nutrient deficiency information in individuals by comparing their metagenomic information to a reference baseline. NURECON integrates a next-generation bacterial 16S rRNA analytical pipeline (QIIME2), metabolic pathway prediction tools (PICRUSt2 and KEGG), and a food compound database (FooDB) to enable the identification of missing nutrients and provide personalized dietary suggestions. Metagenomic information from total number of 287 healthy subjects was used to establish baseline microbial composition and metabolic profiles. The uploaded data is analyzed and compared to the baseline for nutrient deficiency assessment. Visualization results include gut microbial composition, related enzymes, pathways, and nutrient abundance. NURECON is a user-friendly online platform that provides nutritional advice to support dietitians' research or menu design.

Efficacy and Mechanism of the Action of Live and Heat-Killed Bacillus coagulans BC198 as Potential Probiotic in Ameliorating Dextran Sulfate Sodium-Induced Colitis in Mice.

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.

Exploring Phytochemical Mechanisms in the Prevention of Cholesterol Dysregulation: A Review.

Although cholesterol plays a key role in many physiological processes, its dysregulation can lead to several metabolic diseases. Statins are a group of drugs widely used to lower cholesterol levels and cardiovascular risk but may lead to several side effects in some patients. Therefore, the development of a plant-based therapeutic adjuvant with cholesterol-lowering activity is desirable. The maintenance of cholesterol homeostasis encompasses multiple steps, including biosynthesis and metabolism, uptake and transport, and bile acid metabolism; issues arising in any of these processes could contribute to the etiology of cholesterol-related diseases. An increasing body of evidence strongly indicates the benefits of phytochemicals for cholesterol regulation; traditional Chinese medicines prove beneficial in some disease models, although more scientific investigations are needed to confirm their effectiveness. One of the main functions of cholesterol is bile acid biosynthesis, where most bile acids are recycled back to the liver. The composition of bile acid is partly modulated by gut microbes and could be harmful to the liver. In this regard, the reshaping effect of phytochemicals on gut microbiota has been widely reported in the literature for its significance. Therefore, we reviewed studies conducted over the past 5 years elucidating the regulatory effects of phytochemicals or herbal medicines on cholesterol metabolism. In addition, their effects on the recomposition of gut microbiota and bile acid metabolism due to modulation are discussed. This review aims to provide novel insights into the treatment of cholesterol dysregulation and the anticipated development of natural-based compounds in the near and far future.

Trans-2-nonadecyl-4-(hydroxymethyl)-1,3-dioxolane (TNHD) purified from freshwater clams markedly alleviates dimethylnitrosamine-induced hepatic fibrosis.

Liver fibrosis occurs due to injury or inflammation, which results in the excessive production of collagen and the formation of fibrotic scar tissue that impairs liver function. Despite the limited treatment options available, freshwater clams may hold promise in the treatment of liver fibrosis. In this study, we demonstrated the effects of ethanol extract of freshwater clam (FCE), ethyl acetate extract of FCE (EA-FCE), and trans-2-nonadecyl-4-(hydroxymethyl)-1,3-dioxolane (TNHD) on liver fibrosis induced by dimethylnitrosamine (DMN). Administration of FCE and TNHD alleviated liver injury, including tissue damage, necrosis, inflammation scores, fibrosis scores, serum enzymes, and triglyceride levels. Furthermore, we analyzed the expression of fibrosis-related proteins, such as α-smooth muscle actin (α-SMA) and transforming growth factor (TGF-ß), as well as the hydroxyproline content, which decreased after treatment with FCE and TNHD. Animal experiments revealed that FCE and TNHD can reduce liver fibrosis by inhibiting cytokines that activate stellate cells and decreasing extracellular matrix (ECM) secretion. Cell experiments have shown that TNHD inhibits the MAPK/Smad signaling pathway and TGF-ß1 activation, resulting in a reduction in the expression of fibrosis-related proteins. Therefore, freshwater clam extracts, particularly TNHD, may have potential therapeutic and preventive effects for the amelioration of liver fibrosis.

Plant-Derived Extracellular Vesicles: A New Revolutionization of Modern Healthy Diets and Biomedical Applications.

Plant-derived extracellular vesicles (PDEVs) have recently emerged as a promising area of research due to their potential health benefits and biomedical applications. Produced by various plant species, these EVs contain diverse bioactive molecules, including proteins, lipids, and nucleic acids. Increasing in vitro and in vivo studies have shown that PDEVs have inherent pharmacological activities that affect cellular processes, exerting anti-inflammatory, antioxidant, and anticancer activities, which can potentially contribute to disease therapy and improve human health. Additionally, PDEVs have shown potential as efficient and biocompatible drug delivery vehicles in treating various diseases. However, while PDEVs serve as a potential rising star in modern healthy diets and biomedical applications, further research is needed to address their underlying knowledge gaps, especially the lack of standardized protocols for their isolation, identification, and large-scale production. Furthermore, the safety and efficacy of PDEVs in clinical applications must be thoroughly evaluated. In this review, we concisely discuss current knowledge in the PDEV field, including their characteristics, biomedical applications, and isolation methods, to provide an overview of the current state of PDEV research. Finally, we discuss the challenges regarding the current and prospective issues for PDEVs. This review is expected to provide new insights into healthy diets and biomedical applications of vegetables and fruits, inspiring new advances in natural food-based science and technology.

3'-Hydroxypterostilbene Potently Suppresses Tumor Growth via Inhibiting the Activation of the JAK2/STAT3 Pathway in Ovarian Clear Cell Carcinoma.

SCOPE: Ovarian clear cell carcinoma (OCCC) is a subtype of epithelial ovarian cancer (EOC) that is associated with higher interleukin-6 (IL-6) levels, and suppression of the Janus kinase 2/Signal transducer and activator of transription 3 (JAK2/STAT3) pathway may contribute to the suppression of this cancer. This study aims to compare the anti-cancer effect of pterostilbene (PSB) and 2'- and 3'-hydroxypterostilbene (2HPSB and 3HPSB, respectively) on the JAK2/STAT3 pathway. METHODS AND RESULTS: In vitro experiments with the OCCC cell line TOV21G and a xenograft nude mouse model are used to achieve the study aims. The results showed that 3HPSB has the greatest anti-proliferative and pro-apoptotic effects of the three compounds studied. Activation of the JAK2/STAT3 pathway and the nuclear translocation of STAT3 are effectively inhibited by 3HPSB and PSB. Both 3HPSB and PSB can effectively suppress tumor growth, which is mediated by the inhibition of JAK2/STAT3 phosphorylation. CONCLUSION: This is the first study to compare the efficacy of PSB, 3HPSB, and the newly identified compound 2HPSB regarding ovarian cancer. Moreover, targeting JAK2/STAT3 is shown to be a potentially effective strategy for OCCC treatment. This study is expected to provide new insights into the potential of the abovementioned phytochemicals for development as adjuvants for cancer treatment in the future.

Purple Napiergrass (Pennisetum purpureum Schumach) Hot Water Extracts Ameliorate High-Fat Diet-Induced Obesity and Metabolic Disorders in Mice.

Purple Pennisetum (Pennisetum purpureum Schumach), a hybrid between Taihucao No. 2 and the local wild species of purple Pennisetum, has dark red stems and leaves due to its anthocyanin content. This study explores the potential of purple napiergrass extracts (PNE) in alleviating obesity and metabolic disorders induced by a high-fat diet in mice, where 50% of the caloric content is derived from fat. Mice were orally administered low-dose or high-dose PNE alongside a high-fat diet. Experimental findings indicate that PNE attenuated weight gain, reduced liver, and adipose tissue weight, and lowered blood cholesterol, triglyceride, low-density lipoprotein, and blood sugar levels. Stained sections showed that PNE inhibited lipid accumulation and fat hypertrophy in the liver. Immunoblotting analysis suggested that PNE improved the inflammatory response associated with obesity, dyslipidemia, and hyperglycemia induced by a high-fat diet. Furthermore, PNE potentially functions as a PPAR-γ agonist, increasing the adiponectin (ADIPOQ) concentration and suppressing inflammatory factors, while elevating the anti-inflammatory factor interleukin-10 (IL-10) in the liver. PNE-treated mice showed enhanced activation of the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) and AMP-activated protein kinase (AMPK) pathways and increased fatty acid oxidation and liver lipolysis. In conclusion, this study elucidated the mechanisms underlying the anti-inflammatory, PI3K/Akt, and AMPK pathways in a high-fat diet-induced obesity model. These findings highlight the potential of PNE in reducing weight, inhibiting inflammation, and improving blood sugar and lipid levels, showing the potential for addressing obesity-related metabolic disorders in humans.

Virofree Associates with the Modulation of Gut Microbiomes and Alleviation of DSS-Induced IBD Symptoms in Mice.

Inflammatory bowel disease (IBD) is a chronic, nonspecific inflammation of the intestines that primarily comprises Crohn's disease and ulcerative colitis. The incidence and prevalence of IBD have been increasing globally, highlighting the significance of research and prophylactic interventions. Virofree, a mixture of various botanical extracts (including grapes, cherries, olive leaves, marigolds, green tea, and others), has shown significant potential in disease prevention. This study examined the effects of Virofree on intestinal inflammation and the gut microbiota in mice using a dextran sulfate sodium (DSS)-induced model. The mice showed no adverse reactions when administered Virofree. Virofree administration reduced the disease activity index as indicated by amelioration of DSS-induced symptoms in the mice, including weight loss, diarrhea, and rectal bleeding. Regarding the gut microbiota, Virofree intervention modulated the DSS-induced decrease in gut microbial diversity; the Virofree group showed no increase in the phyla Proteobacteria or Verrucomicrobia while displaying an increase in the genus Duncaniella, bacteria that may have protective properties. These findings suggest that Virofree may have a direct or indirect impact on the composition of the gut microbiota and that it can alleviate the imbalance of the microbiome and intestinal inflammation caused by DSS treatment.

Identification of Indicative Gut Microbial Guilds in a Natural Aging Mouse Model.

Gut microbial dysbiosis during later life may contribute to health conditions, possibly due to an increase in intestinal permeability, immune changes, and systemic inflammation. Mouse models have been employed to determine the influence of gut microbes on aging; however, suitable gut microbial indicators are currently lacking. Therefore, this study aimed to determine the gut microbial indicators and their potential guilds in a natural aging mouse model. In agreement with previous studies, alpha diversity indices-including observed OTUs, ACE, Chao1, and Simpson-were significantly lower in aged mice than in younger mice. The results of beta diversity analysis revealed the compositional differences between young and aged mice, and the MRPP, ANOSIM, and Adonis tests indicated that the results were representative. By employing ANCOM and LEfSe analyses, Bacteroides thetaiotaomicron (Bacteroides) and Anaeroplasma were identified as the indicators of young and aged mice, respectively. Notably, these indicators were still present after 3 months. The result of network analysis confirmed the negative correlation of these genera in mice, and the potential guild members were identified based on the increased abundance of Anaeroplasma in aged mice. The gut microbes of aged mice tend to correspond to those involved in human diseases, selenocompound metabolism, and glycolysis/gluconeogenesis in functional predictions. In this study, the gut microbial indicators in aged mice have been identified, and it is envisaged that these findings could provide a new approach for future studies of antiaging.

High Gamma-Aminobutyric Acid (GABA) Oolong Tea Alleviates High-Fat Diet-Induced Metabolic Disorders in Mice.

Obesity and overweight are associated with an increasing risk of developing health conditions and chronic non-communicable diseases, including cardiovascular diseases, cancer, musculoskeletal problems, respiratory problems, and mental health, and its prevalence is rising. Diet is one of three primary lifestyle interventions. Many bioactive components in tea especially oolong tea, including flavonoids, gamma-aminobutyric acid (GABA), and caffeine were reported to show related effects in reducing the risk of obesity. However, the effects of GABA oolong tea extracts (OTEs) on high-fat diet (HFD)-induced obesity are still unclear. Therefore, this study aims to explore whether the intervention of GABA OTEs can prevent HFD-induced obesity and decipher its underlying mechanisms using male C57BL/6 J mice. The result indicated that GABA OTEs reduced leptin expression in epididymal adipose tissue and showed a protective effect on nonalcoholic fatty liver disease. It promoted thermogenesis-related protein of uncoupling protein-1 and peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α), boosted lipid metabolism, and promoted fatty acid oxidation. It also reduced lipogenesis-related protein levels of sterol regulatory element binding protein, acetyl-CoA carboxylase, and fatty acid synthase and inhibited hepatic triglyceride (TG) levels. These data suggest that regular drinking of GABA oolong tea has the potential to reduce the risk of being overweight, preventing obesity development through thermogenesis, lipogenesis, and lipolysis.

Regulation of Xenobiotic-Metabolizing Enzymes by 5-Demethylnobiletin and Nobiletin to Mitigate Benzo[a]pyrene-Induced DNA Damage In Vitro and In Vivo.

Benzo[a]pyrene (B[a]P) is a genotoxic polycyclic aromatic hydrocarbon that is metabolized by cytochrome P450 family 1 enzymes (CYP 1s) and can bind to DNA to form DNA adducts, leading to DNA damage and increased colorectal cancer risk. Previous studies have shown polymethoxyflavones to have a high potential for anticancer effects by regulating CYP 1s, especially nobiletin (NBT) and 5-demethylnobiletin (5-DMNB). However, the effects of NBT and 5-DMNB on B[a]P metabolism remain unclear. Therefore, this study aimed to clarify the effects of NBT and 5-DMNB on B[a]P-induced DNA damage in vitro and in vivo. In NCM460 cells, 5-DMNB and NBT appeared to reduce the metabolic conversion of B[a]P by regulating the aryl hydrocarbon receptor (AhR)/CYP 1s signaling pathway. This process protected NCM460 cells from B[a]P's cytotoxic effects by decreasing DNA damage and suppressing B[a]P diol-epoxide-DNA adduct formation. In BALB/c mice, 5-DMNB and NBT also protected against B[a]P-induced DNA damage. Altogether, these findings indicate that 5-DMNB and NBT attenuate B[a]P-induced DNA damage by modulating biotransformation, highlighting their chemopreventive potential against B[a]P-induced carcinogenesis. Therefore, 5-DMNB and NBT are promising agents for colorectal cancer chemoprevention in the future.

Tangeretin Supplementation Mitigates the Aging Toxicity Induced by Dietary Benzo[a]pyrene Exposure with Aberrant Proteostasis and Heat Shock Responses in Caenorhabditis elegans.

Benzo[a]pyrene (BaP) is a common food contaminant that can impair organismal aging. Tangeretin (TAN) may mitigate aging toxicities as a dietary supplement. This study used Caenorhabditis elegans to investigate the effects of chronic exposure to BaP on aging and to determine whether TAN supplementation could alleviate BaP-induced toxicity. Early life exposure to BaP (10 µM) significantly inhibited growth by 5%, and exposure to 0.1 to 10 µM BaP impaired C. elegans motility, resulting in a 3.4-6.5% reduction in motility. Chronic exposure to BaP (10 µM) age-dependently aggravated aberrant protein aggregation (7% increase) and shortened the median lifespan of the worms from 20 to 16 days. In addition, BaP worsened the age-dependent decline in motility and pharyngeal pumping, as well as the accumulation of reactive oxygen species. Furthermore, exposure to BaP resulted in significantly higher relative transcript levels of approximately 1.8-2.0-fold for the hsp-16.1, hsp-16.2, hsp-16.49, and hsp-70 genes. Stressed worms exposed to BaP exhibited significantly lower survival under heat stress. Dietary TAN supplementation alleviated the BaP-induced decline in motility, pumping, and poly-Q accumulation and restored heat shock proteins' transcript levels. Our findings suggest that chronic BaP exposure adversely affects aging and that TAN exposure mitigates the BaP-induced aging toxicity.

Pterostilbene Enhances Thermogenesis and Mitochondrial Biogenesis by Activating the SIRT1/PGC-1α/SIRT3 Pathway to Prevent Western Diet-Induced Obesity.

SCOPE: Sirtuin 1/peroxisome proliferator-activated receptor gamma co-activator 1 alpha (SIRT1/PGC-1α) pathway activation is known to promote thermogenesis and mitochondrial biogenesis. Pterostilbene (PSB) and pinostilbene (PIN), the methylated analogs of resveratrol, are potential candidates to enhance thermogenesis and mitochondrial biogenesis. METHOD AND RESULTS: A model of Western diet-induced obesity in mice is designed. Either PSB or PIN is supplemented in the diet for 16 weeks. Both samples can significantly reduce body weight gain but only PSB can decrease inguinal adipose tissue weight. Besides, both samples can promote lipolysis but only PSB supplementation activates the SIRT1/PGC-1α/SIRT3 pathway to enhance mitochondrial biogenesis and thermogenesis in the inguinal adipose tissue. In addition, although both samples exert a modulatory effect on gut microbiota but significant increments in fecal isobutyric acid, valeric acid, and isovaleric acid are only observed in the PSB group, functioning as gut microbial metabolites. CONCLUSION: Overall, these findings suggest PSB and PIN as potential candidates for the improvement of obesity and gut microbiota dysbiosis. With its higher stability, PSB exerts a greater effect than PIN by promoting thermogenesis and mitochondrial biogenesis via SIRT1 activation.

Insights from ß-Conglycinin and Glycinin into the Mechanism of Nanoliposome-Soybean Protein Isolate Interactions.

The interaction mechanism between nanoliposomes (NL) and a soybean protein isolate (SPI) was investigated via the complexation between NL and two major components of SPI, i.e., ß-conglycinin (7S) and glycinin (11S). The endogenous fluorescence emissions of 7S and 11S were statically quenched after complexation with NL, and the polarity of the SPI fluorophore increased. The interaction between NL and SPI was exothermic and spontaneous, 7S/11S secondary structures were altered, and more hydrophobic groups were exposed on protein surfaces. Moreover, the NL-SPI complex had a large zeta potential to attain system stability. Hydrophobic forces and hydrogen bonds played vital roles in the interaction between NL and 7S/11S, and a salt bridge was also involved in the NL-11S interaction. The binding characteristics between NL and 7S/11S were chiefly governed by the protein characteristics, such as amino acid composition, surface hydrophobicity, and advanced structure. These findings could deepen the understanding of the interaction mechanism between NL and SPI.

The therapeutic potential of curcumin and its related substances in turmeric: From raw material selection to application strategies.

Turmeric (Curcuma longa L.) is a medicinal plant used extensively in Chinese and Indian traditional medicine as a home remedy for various diseases. It has been used for medical purposes for centuries. Today, turmeric has become one of the most popular medicinal herbs, spices, and functional supplements worldwide. Curcuminoids are linear diary-lheptanoids from the rhizomes that include curcumin and two related compounds: demethoxycurcumin and bisdemethoxycurcumin, which are the active components of the C. longa plant, play a crucial role in numerous functions. This review summarises the composition of turmeric and the properties of curcumin regarding its antioxidant, anti-inflammatory, anti-diabetic, anti-colorectal cancer, and other physiological activity. In addition, the dilemma of the application of curcumin due to its low water solubility and bioavailability was discussed. Finally, this article provides three novel application strategies based on previous studies: using curcumin analogues and related substances, gut microbiota regulation, and using curcumin-loaded exosome vesicles and turmeric-derived exosome-like vesicles to overcome application limitations.

The Role of Mitochondria in Phytochemically Mediated Disease Amelioration.

Mitochondrial dysfunction may cause cell death, which has recently emerged as a cancer prevention and treatment strategy mediated by chemotherapy drugs or phytochemicals. However, most existing drugs cannot target cancerous cells and may adversely affect normal cells via side effects. Mounting studies have revealed that phytochemicals such as resveratrol could ameliorate various diseases with dysfunctional or damaged mitochondria. For instance, resveratrol can regulate mitophagy, inhibit oxidative stress and preserve membrane potential, induce mitochondrial biogenesis, balance mitochondrial fusion and fission, and enhance the functionality of the electron transport chain. However, there are only a few studies suggesting that phytochemicals could potentially protect against the cytotoxicity of some current cancer drugs, especially those that damage mitochondria. Besides, COVID-19 and long COVID have also been reported to be correlated to mitochondrial dysfunction. Curcumin has been reported bringing a positive impact on COVID-19 and long COVID. Therefore, in this study, the benefits of resveratrol and curcumin to be applied for cancer treatment/prevention and disease amelioration were reviewed. Besides, this review also provides some perspectives on phytochemicals to be considered as a treatment adjuvant for COVID-19 and long COVID by targeting mitochondrial rescue. Hopefully, this review can provide new insight into disease treatment with phytochemicals targeting mitochondria.

Prevention of Glutamate-Induced Neurodegeneration by Piceatannol via Mitochondrial Rescue In Vitro and In Vivo.

SCOPE: Parkinson's disease is one of the neurodegenerative diseases that have no cure. Excitotoxicity induced by excess glutamate is known to be a hallmark of these diseases. Therefore, this study aims to evaluate the preventive effect of piceatannol on glutamate-induced neurodegeneration via mitochondrial rescue. METHODS AND RESULTS: The PC12 cell line and three Caenorhabditis elegans (C. elegans) strains are employed to achieve the aim. In the in vitro study, the results show that piceatannol can prevent glutamate-induced apoptosis. Piceatannol also reduces mitochondrial reactive oxygen species (ROS) accumulation by activating the antioxidant system. Moreover, piceatannol can also promote mitochondrial biogenesis and induced mitochondrial fusion-related genes to preserve mitochondrial functionality. In the C. elegans model, piceatannol can prevent mitochondrial fragmentation induced by glutamate. More importantly, piceatannol effectively protects dopaminergic neurons from degradation and preserves the responses controlled by these neurons. CONCLUSION: The findings suggest that piceatannol can be a more effective and potent candidate for the treatment of neurodegenerative diseases, such as Parkinson's disease, compared to resveratrol. It is capable of preventing neurodegeneration induced by excess glutamate, possibly via mitochondrial rescue. It is recommended that piceatannol be developed into a neuroprotective agent.

Cross-Sectional Study: New Approach for Diagnostic Identification of Non-Robust Older Adult.

SCOPE: The aging biomarkers are alternatives and none of them can act as a strong predictor of frailty during the progression of aging. Several studies reveal the relationship between metabolites and frailty or gut microbiota and frailty. However, the connection between metabolites and gut microbiota in non-robust older adults has not been discussed yet. The study aims to combine the findings of serum metabolites and gut microbiota in non-robust subjects as a possible diagnostic biomarker. METHODS AND RESULTS: Frailty-related assessments are conducted to ensure the discrimination of non-robustness. The serum and fecal are collected for serum metabolomics and gut microbiota analysis. Robust and non-robust subjects show very different gut microbial compositions. Among the gut microbial differences, Escherichia/Shigella and its higher taxonomic ranks are found to have the most discriminative abundance among compared groups. More importantly, the abundance of Escherichia/Shigella is found to be positively correlated (p < 0.05) with the level of discriminant metabolites, such as serum oxoglutarate, glutamic acid, and 1-methyladenosine. CONCLUSION: These results indicate the obvious interrelation between gut microbiota and serum metabolites in non-robust older adults. Besides, the findings suggest that Escherichia/Shigella can be a potential biomarker candidate for robustness sub-phenotypic identification.

Protective Effects of Piceatannol on DNA Damage in Benzo[a]pyrene-Induced Human Colon Epithelial Cells.

Evidence shows that the dietary intake of polycyclic aromatic hydrocarbons (PAHs) from food processing induces the cellular DNA damage response and leads to the development of colorectal cancer (CRC). Therefore, protecting from cellular DNA damage might be an effective strategy in preventing CRC. Benzo[a]pyrene (B[a]P) was used as a CRC initiator in the present study. Compared with other stilbenoids, piceatannol (PIC) showed the most effective inhibition of B[a]P-induced cytochrome P450 1B1 (CYP1B1) protein expression in NCM460 normal human colon epithelial cells. PIC treatment alleviated DNA migration and enhanced the expression of DNA-repair-related proteins, including histone 2AX (H2AX), checkpoint kinase 1 (Chk1), and p53, in B[a]P-induced NCM460 cells. The 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA) revealed that PIC exerted antioxidative effects on NCM460 cells by increasing the glutathione (GSH) content and scavenging the excess intracellular reactive oxygen species (ROS) induced by B[a]P. Furthermore, PIC suppressed B[a]P-induced CYP1B1 protein expression and stimulated miR-27b-3p expression. The upregulation of phase II detoxification enzymes, such as nicotinamide adenine dinucleotide phosphate (NADPH) and quinone oxidoreductase 1 (NQO1), and the antioxidative enzyme, heme oxygenase 1 (HO-1), via the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway was observed in the PIC-treated group. Our results suggest that PIC is a potential CRC-blocking agent due to its ability to alleviate DNA damage, decrease intracellular ROS production, modulate the metabolism and detoxification of B[a]P, and activate the Nrf2 signaling pathway in B[a]P-induced NCM460 cells.