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.

S-Allylcysteine Ameliorates Aging Features via Regulating Mitochondrial Dynamics in Naturally Aged C57BL/6J Mice.

SCOPE: S-Allylcysteine (SAC) is the most abundant organosulfur molecule derived from aged garlic. The effects ofSAC on improving Aging in naturally aged C57BL/6J male mice and mitochondrial dynamics in Caenorhabditis elegans and its underlying mechanisms is evaluated. METHODS AND RESULTS: When mice have attained reproductive senescence at 60 weeks of age, SAC is supplemented to 0.05% and 0.2% into their normal diet for 12 weeks. The results show that SAC could significantly improve the level of hepatic optic atrophy 1 (OPA1) mRNA, which is a key factor for mitochondrial fusion, and consequently elevated the mitochondrial biogenesis-related proteins sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1α), thus ameliorating oxidative stress, such as malondialdehyde (MDA) in the liver and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in urine. Among the biochemical markers of aging, SAC significantly reduces liver galactosidase ß1 (GLB1) and senescence-associated ß-galactosidase (SA-ßgal), which are induced by replicative senescence. The mitochondria with green fluorescent protein (GFP)-tagged transgenic strain SJ4103 C. elegans is incubated with 5 or 50 µM SAC, and SAC treated groups maintain the linear morphology of mitochondria. CONCLUSION: SAC regulates mitochondrial dynamics and ameliorated aging to a significant degree. This study also confirms that mitochondrial dynamics are a promising target for screening materials to combat aging and as a direction for anti-aging product development.

Dietary citrate supplementation enhances longevity, metabolic health, and memory performance through promoting ketogenesis.

Citrate is an essential substrate for energy metabolism that plays critical roles in regulating cell growth and survival. However, the action of citrate in regulating metabolism, cognition, and aging at the organismal level remains poorly understood. Here, we report that dietary supplementation with citrate significantly reduces energy status and extends lifespan in Drosophila melanogaster. Our genetic studies in fruit flies implicate a molecular mechanism associated with AMP-activated protein kinase (AMPK), target of rapamycin (TOR), and ketogenesis. Mice fed a high-fat diet that supplemented with citrate or the ketone body ß-hydroxybutyrate (ßOHB) also display improved metabolic health and memory. These results suggest that dietary citrate supplementation may prove to be a useful intervention in the future treatment of age-related dysfunction.

Oxyresveratrol inhibits human colon cancer cell migration through regulating epithelial-mesenchymal transition and microRNA.

The major cause of death in colorectal cancer (CRC) patients is metastasis. Moreover, lots of studies have emphasized that the epithelial-mesenchymal transition (EMT) is a pivotal step in metastasis. Both transforming growth factor beta (TGF-ß) and dysregulation of microRNAs (miRNAs) can induce or regulate EMT, promoting the loss of intercellular adhesion and increased motility of cancer cells. Therefore, it is necessary to prevent or inhibit the metastasis of colorectal cancer. Relatively little is known about the anti-metastatic effect of oxyresveratrol (OXY), a natural derivative of resveratrol (RES), compared to RES. Accordingly, RES was used as the positive control to investigate the effects of OXY on colon cancer cell migration. The results showed that OXY could significantly inhibit cell migration (67.17% ± 0.04, 64.89% ± 0.04) compared to RES (84.6% ± 0.07, 76.34% ± 0.08) in HCT116 cells and TGF-ß-induced HT-29 cells, respectively, via Snail/E-cadherin expression. In addition, OXY improved EMT-related miRNA expression through, for example, lowering the levels of miR-3687 and miR-301a-3p while upregulating miR-3612 in TGF-ß-induced HT-29 cells. In conclusion, OXY inhibits human colon cancer cell migration by regulating EMT and miRNAs. Based on these findings, it can be stated that OXY promotes anti-metastatic properties in CRC.

Occurrence, Bioavailability, Anti-inflammatory, and Anticancer Effects of Pterostilbene.

Supplementation with natural compounds found in fruits and vegetables has long been associated with a reduced risk of several types of cancer. Pterostilbene is a natural stilbenoid and a dimethylated analogue of resveratrol which is found primarily in blueberries. Pterostilbene exhibits a range of pharmacological properties, particularly anti-inflammatory and anticancer effects. Due to two methoxy groups in its skeleton, pterostilbene is more lipophilic than resveratrol and thus possesses higher intestinal permeability and cellular uptake and enhanced stability. Moreover, pterostilbene exhibits less toxicity and fewer adverse effects, providing it with superior potential in cancer chemoprevention and chemotherapy applications. Numerous research studies have demonstrated that pterostilbene possesses detoxification activities, mediating the anti-inflammation response, regulating the cell cycle, augmenting apoptosis, enhancing autophagy, and inhibiting tumor angiogenesis, invasion, and metastasis by modulating signal transduction pathways which block multiple stages of carcinogenesis. In this review, we illustrate that pterostilbene is a natural compound having bioavailability. The extensive metabolism of pterostilbene will be discussed. We also summarize recent research on pterostilbene's anti-inflammatory and anticancer properties in the multistage carcinogenesis process and related molecular mechanism and conclude that it should contribute to improved cancer management.

Epidemiology of pediatric multiple sclerosis, neuromyelitis optica, and optic neuritis in Taiwan.

BACKGROUND AND OBJECTIVE: The epidemiology of pediatric acquired demyelinating disorders remains to be clarified in many parts of Asia. We carry out this study to depict the epidemiology of pediatric multiple sclerosis (MS), neuromyelitis optica (NMO), and optic neuritis (ON) in Taiwan. METHODS: We conducted a retrospective nationwide population-based study using data from Taiwan's National Health Insurance Research Database. Prevalent cases of pediatric MS and NMO during 2001-2015, and incident cases of pediatric MS, NMO, and ON during 2003-2015 were identified. The demographic features and comorbidities were investigated. RESULTS: We identified 403 MS, 42 NMO, and 1496 ON incident cases under the age of 20 during 2003-2015. The majority of pediatric MS (86.1%) and NMO (90.5%) patients were 10 years old or above. The incidence of MS and ON was relatively steady, while that of NMO increased prominently later during the study period. The average incidence of pediatric MS and NMO during 2011-2015 was 0.52 and 0.11 per 100,000 person-years, respectively. The female preponderance was evident for pediatric MS and NMO, and less so for pediatric ON. The most common autoimmune comorbidities for pediatric MS were thyrotoxicosis (1.0%) and systemic lupus erythematosus (0.7%). CONCLUSION: The epidemiology of pediatric MS was largely stationary in Taiwan during 2001-2015, while the prevalence of pediatric NMO rose steeply during this period, probably reflecting better recognition of this clinical entity. Autoimmune comorbidities were uncommon for pediatric MS and NMO in Taiwan.

Ludwigia octovalvis extract improves glycemic control and memory performance in diabetic mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Ludwigia octovalvis (Jacq.) P.H. Raven (Onagraceae) extracts have historically been consumed as a healthful drink for treating various conditions, including edema, nephritis, hypotension and diabetes. AIM OF THE STUDY: We have previously shown that Ludwigia octovalvis extract (LOE) can significantly extend lifespan and improve age-related memory deficits in Drosophila melanogaster through activating AMP-activated protein kinase (AMPK). Since AMPK has become a critical target for treating diabetes, we herein investigate the anti-hyperglycemic potential of LOE. MATERIALS AND METHODS: Differentiated C2C12 muscle cells, HepG2 hepatocellular cells, streptozotocin (STZ)-induced diabetic mice and high fat diet (HFD)-induced diabetic mice were used to investigate the anti-hyperglycemic potential of LOE. The open field test and novel object recognition test were used to evaluate spontaneous motor activity and memory performance of HFD-induced diabetic mice. RESULTS: In differentiated C2C12 muscle cells and HepG2 hepatocellular cells, treatments with LOE and its active component (ß-sitosterol) induced significant AMPK phosphorylation. LOE also enhanced uptake of a fluorescent glucose derivative (2-NBDG) and inhibited glucose production in these cells. The beneficial effects of LOE were completely abolished when an AMPK inhibitor, dorsomorphin, was added to the culture system, suggesting that LOE requires AMPK activation for its action in vitro. In streptozotocin (STZ)-induced diabetic mice, we found that both LOE and ß-sitosterol induced an anti-hyperglycemic effect comparable to that of metformin, a drug that is commonly prescribed to treat diabetes. Moreover, LOE also improved glycemic control and memory performance of mice fed a HFD. CONCLUSIONS: These results indicate that LOE is a potent anti-diabetic intervention that may have potential for future clinical applications.

The anti-aging effects of Ludwigia octovalvis on Drosophila melanogaster and SAMP8 mice.

We investigated the anti-aging effects of Ludwigia octovalvis (Jacq.) P. H. Raven (Onagraceae), an extract of which is widely consumed as a healthful drink in a number of countries. Using the fruit fly, Drosophila melanogaster, as a model organism, we demonstrated that L. octovalvis extract (LOE) significantly extended fly lifespan on a high, but not a low, calorie diet, indicating that LOE may regulate lifespan through a dietary restriction (DR)-related pathway. LOE also attenuated age-related cognitive decline in both flies and in the senescence-accelerated-prone 8 (SAMP8) mouse, without causing any discernable negative trade-offs, including water intake, food intake, fecundity, or spontaneous motor activity. LOE contained high levels of polyphenols and flavonoids, which possess strong DPPH radical scavenging activity, and was shown to attenuate paraquat-induced oxidative damage and lethality in flies. Gas chromatography-mass spectrometry (GC-MS) analyses identified 17 known molecules, of which ß-sitosterol and squalene were the two most abundant. We further demonstrated that ß-sitosterol was capable of extending lifespan, likely through activating AMP-activated protein kinase (AMPK) in the fat body of adult flies. Taken together, our data suggest that LOE is a potent anti-aging intervention with potential for treating age-related disorders.