Svyatoslav Dvoretskiy

Background: The prevalence of vascular dysfunction increases with advancing age, as does the loss of muscle mass, strength and function. This systematic review explores the association between vascular dysfunction and skeletal muscle health in healthy adults. Methods: EMBASE and MEDLINE were searched for cross-sectional and randomized controlled studies between January 2009 and April 2019, with 33 out of 1246 studies included based on predefined criteria. Assessments of muscular health included muscle mass, strength and function. Macrovascular function assessment included arterial stiffness (pulse wave velocity or augmentation index), carotid intima-media thickness, and flow-mediated dilation. Microvascular health assessment included capillary density or microvascular flow (contrast enhanced ultrasound). Results: All 33 studies demonstrated a significant association between vascular function and skeletal muscle health. Significant negative associations were reported between vascular dysfunction and -muscle strength (10 studies); -mass (9 studies); and -function (5 studies). Nine studies reported positive correlations between muscle mass and microvascular health. Conclusions: Multiple studies have revealed an association between vascular status and skeletal muscle health in healthy adults. This review points to the importance of screening for muscle health in adults with vascular dysfunction with a view to initiating early nutrition and exercise interventions to ameliorate functional decline over time.

Background: Five of the most abundant human milk oligosaccharides (HMOs) in human milk are 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL). Methods: A randomized, double-blind, controlled parallel feeding trial evaluated growth in healthy term infants fed a control milk-based formula (CF; n = 129), experimental milk-based formula (EF; n = 130) containing five HMOs (5.75 g/L; 2′-FL, 3-FL, LNT, 3′-SL and 6′-SL) or human milk (HM; n = 104). Results: No significant differences (all p ≥ 0.337, protocol evaluable cohort) were observed among the three groups for weight gain per day from 14 to 119 days (D) of age, irrespective of COVID-19 or combined non-COVID-19 and COVID-19 periods. There were no differences (p ≥ 0.05) among the three groups for gains in weight and length from D14 to D119. Compared to the CF group, the EF group had more stools that were soft, frequent and yellow and were similar to the HM group. Serious and non-serious adverse events were not different among groups, but more CF-fed infants were seen by health care professionals for illness from study entry to D56 (p = 0.044) and D84 (p = 0.028) compared to EF-fed infants. Conclusions: The study demonstrated that the EF containing five HMOs supported normal growth, gastrointestinal (GI) tolerance and safe use in healthy term infants.

Since the U.S. Institute of Medicine's recommendations on protein and amino acid intake in 2005, new information supports the need to re-evaluate these recommendations. New lines of evidence include: (1) re-analysis/re-interpretation of nitrogen balance data; (2) results from indicator amino acid oxidation studies; (3) studies of positive functional outcomes associated with protein intakes higher than recommended; (4) dietary guidance and protein recommendations from some professional nutrition societies; and (5) recognition that the synthesis of certain dispensable amino acids may be insufficient to meet physiological requirements more often than previously understood. The empirical estimates, theoretical calculations and clinical functional outcomes converge on a similar theme, that recommendations for intake of protein and some amino acids may be too low in several populations, including for older adults (≥65 years), pregnant and lactating women, and healthy children older than 3 years. Additional influential factors that should be considered are protein quality that meets operational sufficiency (adequate intake to support healthy functional outcomes), interactions between protein and energy intake, and functional roles of amino acids which could impact the pool of available amino acids for use in protein synthesis. Going forward, the definition of "adequacy" as it pertains to protein and amino acid intake recommendations must take into consideration these critical factors.

Cholesterol has been implicated in the clinical progression of breast cancer, a disease that continues to be the most commonly diagnosed cancer in women. Previous work has identified the cholesterol metabolite 27-hydroxycholesterol (27HC) as a major mediator of the effects of cholesterol on breast tumor growth and progression. 27HC can act as an estrogen receptor (ER) modulator to promote the growth of ERα+ tumors, and as a liver X receptor (LXR) ligand in myeloid immune cells to establish an immune-suppressive program. In fact, the metastatic properties of 27HC require the presence of myeloid cells with neutrophils (polymorphonuclear neutrophils; PMNs) being essential for the increase in lung metastasis in murine models. In an effort to further elucidate the mechanisms by which 27HC alters breast cancer progression, we made the striking finding that 27HC promoted the secretion of extracellular vesicles (EVs), a diverse assortment of membrane bound particles that includes exosomes. The resulting EVs had a size distribution that was skewed slightly larger than EVs generated by treating cells with vehicle. The increase in EV secretion and size was consistent across 3 different subtypes: primary murine PMNs, RAW264.7 monocytic cells, and 4T1 murine mammary cancer cells. Label-free analysis of 27HC-EVs indicated that they had a different metabolite composition to those from vehicle-treated cells. Importantly, 27HC-EVs from primary PMNs promoted tumor growth and metastasis in 2 different syngeneic models, demonstrating the potential role of 27HC-induced EVs in the progression of breast cancer. EVs from PMNs were taken up by cancer cells, macrophages, and PMNs, but not T cells. Since EVs did not alter proliferation of cancer cells, it is likely that their protumor effects are mediated through interactions with myeloid cells. Interestingly, RNA-seq analysis of tumors from 27HC-EV-treated mice do not display significantly altered transcriptomes, suggesting that the effects of 27HC-EVs occur early on in tumor establishment and growth. Future work will be required to elucidate the mechanisms by which 27HC increases EV secretion, and how these EVs promote breast cancer progression. Collectively, however, our data indicate that EV secretion and content can be regulated by a cholesterol metabolite, which may have detrimental effects in terms of disease progression, important findings given the prevalence of both breast cancer and hypercholesterolemia.

Background: MicroRNAs have altered expression levels in various diseases and may play an important role in the diagnosis and prognosis of colorectal cancer (CRC). Methods: We systemically reviewed and quantitatively synthesized the scientific evidence pertaining to microRNA-20a (miR-20a) as a CRC biomarker. A keyword and reference search in PubMed yielded 32 studies, in which miR-20a was measured in feces, serum, or tumor tissue. Data were extracted from a total of 5014 cancer cases and 2863 controls. Results: Twenty out of 21 relevant studies found that miR-20a was upregulated in CRC patients compared to controls. Meta-analysis revealed a pooled miR-20a fold change of 2.45 (95% CI: 2.24–2.66) in CRC patients versus controls. To estimate sensitivity and specificity of miR-20a as a diagnostic biomarker of CRC, a pooled area under the receiver operating characteristic curve (AUROC) was calculated (0.70, 95% CI: 0.63–0.78). The prognostic capacity of miR-20a was assessed using hazard ratios (HRs) for the overall survival (OS). The meta-analysis estimated the pooled HR for OS to be 2.02 (95% CI: 0.90–3.14) in CRC patients with high miR-20a expression. Conclusions: miR-20a may be a valid biomarker for CRC detection but may not be a strong predictor of poor prognosis in CRC.