The therapeutic benefits of mesenchymal stromal cell (MSC) transplantation are attributed to their secreted factors, including extracellular vesicles (EVs) and soluble factors. The potential of ...employing the MSC secretome as an alternative acellular approach to cell therapy is being investigated in various tissue injury indications, but EVs administered via bolus injections are rapidly sequestered and cleared. However, biomaterials offer delivery platforms to enhance EV retention rates and healing efficacy. This review highlights the mechanisms underpinning the therapeutic effects of MSC‐EVs and soluble factors as effectors of immunomodulation and tissue regeneration, conferred primarily via their nucleic acid and protein contents. Discussed is how manipulating the cell culture microenvironment or genetic modification of MSCs can further augment the potency of their secretions. The most recent advances in the development of EV‐functionalized biomaterials that mediate enhanced angiogenesis and cell survival, while attenuating inflammation and fibrosis, are presented. Finally, some technical challenges to be considered for the clinical translation of biomaterials carrying MSC‐secreted bioactive cargo are discussed.
The regenerative potential of extracellular vesicles and soluble factors secreted by mesenchymal stem/stromal cells (MSCs) is reviewed. The role of the cell culture environment in modulating the functionality of these secretions, and how biomaterials are harnessed to deliver the MSC secretome in a targeted and controlled manner are highlighted.
Fusobacterium nucleatum has long been found to cause opportunistic infections and has recently been implicated in colorectal cancer; however, it is a common member of the oral microbiota and can have ...a symbiotic relationship with its hosts. To address this dissonance, we explore the diversity and niches of fusobacteria and reconsider historic fusobacterial taxonomy in the context of current technology. We also undertake a critical reappraisal of fusobacteria with a focus on F. nucleatum as a mutualist, infectious agent and oncogenic microorganism. In this Review, we delve into recent insights and future directions for fusobacterial research, including the current genetic toolkit, our evolving understanding of its mechanistic role in promoting colorectal cancer and the challenges of developing diagnostics and therapeutics for F. nucleatum.
Colorectal cancer is the second-leading cause of cancer-related deaths in the United States and fourth-leading cause of cancer-related deaths worldwide. While cancer is largely considered to be a ...disease of genetic and environmental factors, increasing evidence has demonstrated a role for the microbiota (the microorganisms associated with the human body) in shaping inflammatory environments and promoting tumor growth and spread. Herein, we discuss both human data from meta'omics analyses and data from mechanistic studies in cell culture and animal models that support specific bacterial agents as potentiators of tumorigenesis-including
Fusobacterium nucleatum
, enterotoxigenic
Bacteroides fragilis
, and colibactin-producing
Escherichia coli
. Further, we consider how microbes can be used in diagnosing colorectal cancer and manipulating the tumor environment to encourage better patient outcomes in response to immunotherapy treatments.
Reducing the incidence or prevalence of any disease by 40% is of huge public health significance. Slowing myopia by 1 diopter may do just that for myopic maculopathy-the most common and serious ...sight-threatening complication of myopia. There is a growing interest in slowing the progression of myopia due to its increasing prevalence around the world, the sight-threatening consequences of higher levels of myopia, and the growing evidence-based literature supporting a variety of therapies for its control. We apply data from five large population-based studies of the prevalence of myopic maculopathy on 21,000 patients. We show that a 1-diopter increase in myopia is associated with a 67% increase in the prevalence of myopic maculopathy. Restated, slowing myopia by 1 diopter should reduce the likelihood of a patient developing myopic maculopathy by 40%. Furthermore, this treatment benefit accrues regardless of the level of myopia. Thus, while the overall risk of myopic maculopathy is higher in a -6-diopter myope than in a -3-diopter myope, slowing their myopic progression by 1 diopter during childhood should lower the risk by 40% in both.
In this randomized trial of financial incentives in smokers, both reward-based and deposit-based incentive programs were more effective than usual care in achieving smoking cessation. Reward programs ...were much more commonly accepted than deposit-based programs.
Financial incentives have been shown to promote a variety of health behaviors.
1
–
8
For example, in a randomized, clinical trial involving 878 General Electric employees, a bundle of incentives worth $750 for smoking cessation nearly tripled quit rates, from 5.0% to 14.7%,
8
and led to a program adapted by General Electric for its U.S. employees.
9
Although incentive programs are increasingly used by governments, employers, and insurers to motivate changes in health behavior,
10
,
11
their design is usually based on the traditional economic assumption that the size of the incentive determines its effectiveness. In contrast, behavioral economic theory suggests that incentives . . .
Bacteria, such as Fusobacterium nucleatum, are present in the tumor microenvironment. However, the immunological consequences of intra-tumoral bacteria remain unclear. Here, we have shown that ...natural killer (NK) cell killing of various tumors is inhibited in the presence of various F. nucleatum strains. Our data support that this F. nucleatum-mediated inhibition is mediated by human, but not by mouse TIGIT, an inhibitory receptor present on all human NK cells and on various T cells. Using a library of F. nucleatum mutants, we found that the Fap2 protein of F. nucleatum directly interacted with TIGIT, leading to the inhibition of NK cell cytotoxicity. We have further demonstrated that tumor-infiltrating lymphocytes expressed TIGIT and that T cell activities were also inhibited by F. nucleatum via Fap2. Our results identify a bacterium-dependent, tumor-immune evasion mechanism in which tumors exploit the Fap2 protein of F. nucleatum to inhibit immune cell activity via TIGIT.
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•Bran protein components isolated from wheat, barley and oat.•Protein degradation followed using an in vitro digestion system.•Bioactive peptides identified.
An alkaline extraction ...method has been used in many studies to extract total protein from cereal samples. Wheat bran protein concentrate (WBPC), oat bran protein concentrate (OBPC), and barley protein concentrate (BPC) were prepared by alkaline extraction and isoelectric precipitation to study their functional and nutritional properties. The three protein concentrates were hydrolysed by an in vitro pepsin-pancreatin digestion model. Their digestibility (%) and degree of hydrolysis (DH%) were evaluated, and SDS-PAGE electrophoresis was used to illustrate the protein and peptides patterns. The change of the particle sizes and the release of the essential amino acids was followed during the digestion process. The in vitro digestibility of WBPC, OBPC and BPC was 87.4%, 96.1% and 76.9%, respectively. The DH% of protein concentrates were between 50 and 60%. The change of the particle size distribution values Dv(50) was assumed to be related to protein aggregations during the digestion. The protein fractions were identified and the degradation during the digestion and were analysed by SDS-PAGE; the gels of WBPC and OBPC digestion showed virtually complete degradation whereas the intensive bands of undigested protein were presented for BPC. The generation of the free amino acids and short chain peptides were significantly higher at the end of the intestinal digestion compared to the stages of before and after gastric digestion. Higher content of the deficient amino acids such as lysine and threonine were found comparing to the level of deficient amino acids in cereal grains but does not meet the daily recommended intake.
Summary
Consumer appeal for ready‐to‐eat (RTE) products is forecast to grow rapidly over the next 5 years as consumers demand convenient snacks with exciting sensory and textural properties. ...Extrusion technology has been used extensively in the production of cereal RTE snacks due to its ease of operation and ability to produce a variety of textures and shapes which appeal to consumers. Many of the existing RTE products are relatively high in sugar and salt, thus being regarded as energy dense but nutritionally poor foods. However, there exists a potential to manipulate the nutritional status of extruded RTEs by altering the digestion potentials of starch and protein, and by the incorporation of bioactive components such as dietary fibre. The review article explores some of the recent research in this field and illustrates opportunities by which the global food industry could react to consumers' requirements for healthful RTE snack products in the coming years.
Appreciation of the role of the gut microbiome in regulating vertebrate metabolism has exploded recently. However, the effects of gut microbiota on skeletal growth and homeostasis have only recently ...begun to be explored. Here, we report that colonization of sexually mature germ-free (GF) mice with conventional specific pathogen-free (SPF) gut microbiota increases both bone formation and resorption, with the net effect of colonization varying with the duration of colonization. Although colonization of adult mice acutely reduces bone mass, in long-term colonized mice, an increase in bone formation and growth plate activity predominates, resulting in equalization of bone mass and increased longitudinal and radial bone growth. Serum levels of insulin-like growth factor 1 (IGF-1), a hormone with known actions on skeletal growth, are substantially increased in response to microbial colonization, with significant increases in liver and adipose tissue IGF-1 production. Antibiotic treatment of conventional mice, in contrast, decreases serum IGF-1 and inhibits bone formation. Supplementation of antibiotic-treated mice with short-chain fatty acids (SCFAs), products of microbial metabolism, restores IGF-1 and bone mass to levels seen in nonantibiotic-treated mice. Thus, SCFA production may be one mechanism by which microbiota increase serum IGF-1. Our study demonstrates that gut microbiota provide a net anabolic stimulus to the skeleton, which is likely mediated by IGF-1. Manipulation of the microbiome or its metabolites may afford opportunities to optimize bone health and growth.
Certain
strains residing in the human gut produce colibactin, a small-molecule genotoxin implicated in colorectal cancer pathogenesis. However, colibactin's chemical structure and the molecular ...mechanism underlying its genotoxic effects have remained unknown for more than a decade. Here we combine an untargeted DNA adductomics approach with chemical synthesis to identify and characterize a covalent DNA modification from human cell lines treated with colibactin-producing
Our data establish that colibactin alkylates DNA with an unusual electrophilic cyclopropane. We show that this metabolite is formed in mice colonized by colibactin-producing
and is likely derived from an initially formed, unstable colibactin-DNA adduct. Our findings reveal a potential biomarker for colibactin exposure and provide mechanistic insights into how a gut microbe may contribute to colorectal carcinogenesis.
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