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.
Regular exercise is crucial for maintaining cognitive health throughout life. Recent evidence suggests muscle contractions during exercise release factors into the blood which cross into the brain ...and stimulate adult hippocampal neurogenesis. However, no study has tested whether muscle contractions alone are sufficient to increase adult hippocampal neurogenesis and improve behavioral performance. Adult male, C57BL/6J mice were anesthetized and exposed to bilateral hind limb muscle contractions (both concentric and eccentric) via electrical stimulation (e-stim) of the sciatic nerve twice a week for 8 weeks. Each session lasted approximately 20 min and consisted of a total of 40 muscle contractions. The control group was treated similarly except without e-stim (sham). Acute neuronal activation of the dentate gyrus (DG) using cFos immunohistochemistry was measured as a negative control to confirm that the muscle contractions did not activate the hippocampus, and in agreement, no DG activation was observed. Relative to sham, e-stim training increased DG volume by approximately 10% and astrogliogenesis by 75%, but no difference in neurogenesis was detected and no improvement in behavioral performance was observed. E-stim also increased astrogliogenesis in CA1/CA2 hippocampal subfields but not in the cortex. Results demonstrate that muscle contractions alone, in absence of DG activation, are sufficient to increase adult hippocampal astrogliogenesis, but not neurogenesis or behavioral performance in mice.
Stem cell transplantation has been a promising treatment for peripheral arterial diseases in the past decade. Stem cells act as living bioreactors of paracrine factors that orchestrate tissue ...regeneration. Prestimulated adipose-derived stem cells (ADSCs) have been proposed as potential candidates but have been met with challenges in activating their secretory activities for clinical use. Here, we propose that tethering the ADSC surface with nanoparticles releasing tumor necrosis factor α (TNFα), named nanostimulator, would stimulate cellular secretory activity in situ. We examined this hypothesis by complexing octadecylamine-grafted hyaluronic acid onto a liposomal carrier of TNFα. Hyaluronic acid increased the liposomal stability and association to CD44 on ADSC surface. ADSCs tethered with these TNFα carriers exhibited up-regulated secretion of proangiogenic vascular endothelial growth factor and immunomodulatory prosteoglandin E2 (PGE2) while decreasing secretion of antiangiogenic pigment epithelium-derived factors. Accordingly, ADSCs tethered with nanostimulators promoted vascularization in a 3D microvascular chip and enhanced recovery of perfusion, walking, and muscle mass in a murine ischemic hindlimb compared to untreated ADSCs. We propose that this surface tethering strategy for in situ stimulation of stem cells would replace the costly and cumbersome preconditioning process and expedite clinical use of stem cells for improved treatments of various injuries and diseases.
: MicroRNAs have altered expression levels in various diseases and may play an important role in the diagnosis and prognosis of colorectal cancer (CRC).
: 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.
: 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.
: miR-20a may be a valid biomarker for CRC detection but may not be a strong predictor of poor prognosis in CRC.
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.
: 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.
: 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).
: 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.
: 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.
Introduction
Stunting is a devastating consequence of poor nutrition from before birth to early childhood. While the prevalence of stunting is decreasing over the past 30 years, approximately 144 ...million children still suffer from stunting globally and 5 million in Latin America (LATAM).
Method
The purpose of this review is to provide an overview of stunting globally, with a focus on LATAM. Stunting can impact child development, lead to greater susceptibility to infections, increase functional impairments, and increase mortality risks. Furthermore, the economic negative impact of stunting is large, as stunted children will likely suffer from productivity losses due to chronic diseases in adulthood. The reduction in per capita income of the labor force due to stunting is close to 5% in LATAM; therefore, there is a continued need for comprehensive approaches to address stunting in this region and around the globe.
Conclusions
A multisectoral comprehensive approach to address stunting is required, with nutritional intervention being a key part of that process.
Radiation-induced oral mucositis (RIOM) is a painful, dose-limiting toxicity in cancer therapy. RIOM was induced by radiation on the left buccal pouch mucosa of Golden Syrian hamsters (n = 8/group). ...Animals were treated topically with polyphenols (Curcumin or Quercetin) or amino acids/metabolite mixtures (Alanyl-Glutamine or Arginine + Glutamine + β-Hydroxy β-methylbutyric acid (Arg/Gln/HMB)) for over 20 day. Progression of RIOM was assessed using a standard visual scoring six-point scale, for differences in severity of mucositis (score ≥3) (Chi-square analysis) and in the daily group scores (Mann-Whitney rank sum test). Compared to the controls, there was a significant reduction in number of days with severe RIOM (score ≥3) in the treatment groups: Curcumin (50 μg/ml) = 17%; Control = 38.5%, p < 0.001; Quercetin (50 μg/ml) = 27.6% and Quercetin (100 μg/ml) = 25%; Control = 41.3%, p = 0.007 and p = 0.001, respectively; Arg/Gln/HMB (50 mg/ml) = 31.9%; Control = 50.0%, p = 0.040. In addition, Curcumin (50 μg/ml), Quercetin (100 μg/ml) and Arg/Gln/HMB (100 mg/ml) groups had lower mucositis scores (≥3) on at least two consecutive time points over the course of the study than their respective controls. There were no significant group differences in deaths or body weight. This study demonstrates the potential benefits of topical application of either plant polyphenols or amino acid/metabolite mixtures in addressing severity and progression of RIOM.
Extended bed rest or limb immobilization can significantly reduce skeletal muscle mass and function. Recovery may be incomplete, particularly in older adults. Our laboratory recently reported that ...vascular mural cell (pericyte) quantity is compromised after immobilization and appropriate replacement immediately before remobilization can effectively recover myofiber size in mice. Identification of a single cell surface marker for isolation of the most therapeutic pericyte would streamline efforts to optimize muscle recovery. The purpose of this study was to compare the capacity for neural/glial antigen 2 (Cspg4/NG2
) and melanoma cell adhesion molecule (Mcam/CD146
) positive pericytes to uniquely recover skeletal muscle post-disuse. A single hindlimb from adult C57BL/6J mice was immobilized in full dorsiflexion via a surgical staple inserted through the center of the foot and body of the gastrocnemius. Fourteen days after immobilization, the staple was removed and pericytes, either NG2
CD45
CD31
Lin
, CD146
NG2
Lin
, or CD146
Lin
pericytes, were injected into the atrophied tibialis anterior (TA) muscle. TA muscles were excised 14 days after transplantation and remobilization. Pericyte transplantation did not significantly improve muscle mass or myofiber cross-sectional area (CSA) after 14 days of remobilization. However, injection of CD146
pericytes significantly increased Type IIa quantity, capillarization, and collagen remodeling compared with NG2
pericytes (
< 0.05). Our results suggest that selection of pericytes based on CD146 rather than NG2 results in the isolation of therapeutic mural cells with high capacity to positively remodel skeletal muscle after a period of immobilization.
In this study, pericytes were isolated from mouse skeletal muscle based on cell surface marker expression of neural/glial antigen 2 (NG2) or melanoma cell adhesion molecule (Mcam/CD146) and then compared for the capacity to recover skeletal muscle after a period of immobilization in recipient mice. We report that CD146
Lin
pericytes exhibit higher capacity than NG2
Lin
pericytes to recover Type IIa fiber quantity, capillary content, and collagen turnover after disuse.
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