Promotion of healthy aging through the nexus of gut microbiota and dietary phytochemicals.

Aging is associated with the decline of tissue and cellular functions, which can promote the development of age-related diseases like cancer, cardiovascular disease, neurodegeneration, and disorders of the musculoskeletal and immune systems. Healthspan is the length of time an individual is in good health and free from chronic diseases and disabilities associated with aging. Two modifiable factors that can influence healthspan, promote healthy aging, and prevent the development of age-related diseases, are the diet and microbiota in the gastrointestinal tract (gut microbiota).

Using Otoliths to Understand Historic and Contemporary Selenium Exposure in Kokanee Salmon (Oncorhynchus nerka) in Kluane National Park and Reserve, Yukon Territory.

The Kokanee salmon population in Kluane National Park and Reserve (Yukon Territory) declined significantly between 2002 and 2012. Elevated levels of selenium (Se), which can affect fish reproduction, were recently measured in waters used by spawning Kokanee. To investigate whether Se may be contributing to long-term population declines, and in the absence of long-term data on aqueous Se concentrations, Se concentrations in sagittal otoliths - fish ear-bones that chronicle lifetime exposure - were measured and compared in Kokanee sampled in 1981 (a year with many spawners) and 2019-2021.

P-cadherin mechanoactivates tumor-mesothelium metabolic coupling to promote ovarian cancer metastasis.

Cancer adhesion to the mesothelium is critical for peritoneal metastasis, but how metastatic cells adapt to the biomechanical microenvironment remains unclear. Our study demonstrates that highly metastatic (HM), but not non-metastatic, ovarian cancer cells selectively activate the peritoneal mesothelium. HM cells exert a stronger adhesive force on mesothelial cells via P-cadherin, an adhesion molecule abundant in late-stage tumors.

N6-Methyladenosine modification activates the serine synthesis pathway to mediate therapeutic resistance in liver cancer.

Metabolic adaptation serves as a significant driving force for cancer growth and poses a substantial obstacle for cancer therapies. Herein, we unraveled the role of m6A-mediated serine synthesis pathway (SSP) regulation in both hepatocellular carcinoma (HCC) development and therapeutic resistance. We demonstrated that treatment of highly specific m6A inhibitor (STM2457) effectively inhibited HCC cell line growth and suppressed spontaneous HCC formation in mice driven by liver-specific Tp53 knockout and Myc overexpression.

The immune microenvironment of steatotic hepatocellular carcinoma: Current findings and future prospects.

Hepatocellular carcinoma (HCC), the major type of primary liver cancer, is notorious for its resistance to systemic treatments. The field has made a great leap in the past decade, with the number of FDA-approved therapies for advanced HCC increasing from 1 to 9. Although tyrosine kinase inhibitors remain the most common first-line option as monotherapy treatment, the clinical success of immune checkpoint inhibitors, especially when used in combination with anti-VEGF/VEGFR in HCC will likely transform the treatment landscape.

Identification of biological signatures of cruciferous vegetable consumption utilizing machine learning-based global untargeted stable isotope traced metabolomics.

In recent years there has been increased interest in identifying biological signatures of food consumption for use as biomarkers. Traditional metabolomics-based biomarker discovery approaches rely on multivariate statistics which cannot differentiate between host- and food-derived compounds, thus novel approaches to biomarker discovery are required to advance the field. To this aim, we have developed a new method that combines global untargeted stable isotope traced metabolomics and a machine learning approach to identify biological signatures of cruciferous vegetable consumption.

Bone Marrow Adipose Tissue Is Not Required for Reconstitution of the Immune System Following Irradiation in Male Mice.

Bone marrow adipose tissue (BMAT) is hypothesized to serve as an expandable/contractible fat depot which functions, in part, to minimize energy requirements for sustaining optimal hematopoiesis. We investigated whether BMAT is required for immune reconstitution following injury. Male wild type (WBB6F1, WT) and BMAT-deficient WBB6F1/J-/J () mice were lethally irradiated.

Gut enterotype-dependent modulation of gut microbiota and their metabolism in response to xanthohumol supplementation in healthy adults.

Xanthohumol (XN), a polyphenol found in the hop plant (), has antioxidant, anti-inflammatory, prebiotic, and anti-hyperlipidemic activity. Preclinical evidence suggests the gut microbiome is essential in mediating these bioactivities; however, relatively little is known about XN's impact on human gut microbiota . We conducted a randomized, triple-blinded, placebo-controlled clinical trial (ClinicalTrials.

Genomic vulnerability of a freshwater salmonid under climate change.

Understanding the adaptive potential of populations and species is pivotal for minimizing the loss of biodiversity in this era of rapid climate change. Adaptive potential has been estimated in various ways, including based on levels of standing genetic variation, presence of potentially beneficial alleles, and/or the severity of environmental change. Kokanee salmon, the non-migratory ecotype of sockeye salmon (), is culturally and economically important and has already been impacted by the effects of climate change.

Catalytic activity of OGG1 is impaired by Zinc deficiency.

Oxidative stress-induced DNA base modifications, if unrepaired, can increase mutagenesis and genomic instability, ultimately leading to cell death. Cells predominantly use the base excision repair (BER) pathway to repair oxidatively-induced non-helix distorting lesions. BER is initiated by DNA glycosylases, such as 8-oxoguanine DNA glycosylase (OGG1), which repairs oxidatively modified guanine bases, including 7,8-dihydro-8-oxoguanine (8-oxoG) and ring-opened formamidopyrimidine lesions, 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG).

Sulforaphane and Sulforaphane-Nitrile Metabolism in Humans Following Broccoli Sprout Consumption: Inter-individual Variation, Association with Gut Microbiome Composition, and Differential Bioactivity.

Scope: The glucosinolate glucoraphanin from broccoli is converted to sulforaphane (SFN) or sulforaphane-nitrile (SFN-NIT) by plant enzymes or the gut microbiome. Human feeding studies typically observe high inter-individual variation in absorption and excretion of SFN, however, the source of this variation is not fully known. To address this, a human feeding trial to comprehensively evaluate inter-individual variation in the absorption and excretion of all known SFN metabolites in urine, plasma, and stool, and tested the hypothesis that gut microbiome composition influences inter-individual variation in total SFN excretion has been conducted.

Inhibition of CAF-1 histone chaperone complex triggers cytosolic DNA and dsRNA sensing pathways and induces intrinsic immunity of hepatocellular carcinoma.

Background And Aims: Chromatin assembly factor 1 (CAF-1) is a replication-dependent epigenetic regulator that controls cell cycle progression and chromatin dynamics. In this study, we aim to investigate the immunomodulatory role and therapeutic potential of the CAF-1 complex in HCC.

Approach And Results: CAF-1 complex knockout cell lines were established using the CRISPR/Cas9 system.

Higher weight in partially leptin-resistant db/+ mice is associated with positive effects on bone.

Absence of leptin confers metabolic dysfunction resulting in morbid obesity. Bone growth and maturation are also impaired. Partial leptin resistance is more common than leptin deficiency and, when induced by feeding mice a high fat diet, often has a negative effect on bone.

Sulforaphane Bioavailability in Healthy Subjects Fed a Single Serving of Fresh Broccoli Microgreens.

Cruciferous vegetable consumption is associated with numerous health benefits attributed to the phytochemical sulforaphane (SFN) that exerts antioxidant and chemopreventive properties, among other bioactive compounds. Broccoli sprouts, rich in SFN precursor glucoraphanin (GRN), have been investigated in numerous clinical trials. Broccoli microgreens are similarly rich in GRN but have remained largely unexplored.