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Leaf-Inspired Authentically Complex Microvascular Networks for Deciphering Biological Transport Process.
Miali, ME, Colasuonno, M, Surdo, S, Palomba, R, Pereira, R, Rondanina, E, Diaspro, A, Pascazio, G, Decuzzi, P
ACS applied materials & interfaces. 2019;(35):31627-31637
Abstract
The vascular transport of molecules, cells, and nanoconstructs is a fundamental biophysical process impacting tissue regeneration, delivery of nutrients and therapeutic agents, and the response of the immune system to external pathogens. This process is often studied in single-channel microfluidic devices lacking the complex tridimensional organization of vascular networks. Here, soft lithography is employed to replicate the vein system of a Hedera elix leaf on a polydimethilsiloxane (PDMS) template. The replica is then sealed and connected to an external pumping system to realize an authentically complex microvascular network. This satisfies energy minimization criteria by Murray's law and comprises a network of channels ranging in size from capillaries (∼50 μm) to large arterioles and venules (∼400 μm). Micro-PIV (micro-particle image velocimetry) analysis is employed to characterize flow conditions in terms of streamlines, fluid velocity, and flow rates. To demonstrate the ability to reproduce physiologically relevant transport processes, two different applications are demonstrated: vascular deposition of tumor cells and lysis of blood clots. To this end, conditions are identified to culture cells within the microvasculature and realize a confluent endothelial monolayer. Then, the vascular deposition of circulating breast (MDA-MB 231) cancer cells is documented throughout the network under physiologically relevant flow conditions. Firm cell adhesion mostly occurs in channels with low mean blood velocity. As a second application, blood clots are formed within the chip by mixing whole blood with a thrombin solution. After demonstrating the blood clot stability, tissue plasminogen activator (tPA) and tPA-carrying nanoconstructs (tPA-DPNs) are employed as thrombolytics. In agreement with previous data, clot dissolution is equally induced by tPA and tPA-DPNs. The proposed leaf-inspired chip can be efficiently used to study a variety of vascular transport processes in complex microvascular networks, where geometry and flow conditions can be modulated and monitored throughout the experimental campaign.
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Safety of TeaCrine®, a non-habituating, naturally-occurring purine alkaloid over eight weeks of continuous use.
Taylor, L, Mumford, P, Roberts, M, Hayward, S, Mullins, J, Urbina, S, Wilborn, C
Journal of the International Society of Sports Nutrition. 2016;:2
Abstract
BACKGROUND Theacrine (1,3,7,9-tetramethyluric acid) is a purine alkaloid found in certain coffee (Coffea) species, fruits (Cupuacu [Theobroma grandiflorum]), and tea (Camellia assamica, var. kucha) that has anti-inflammatory, analgesic, and neuro-locomotor properties. Recent preliminary research has also reported increased feelings of energy, reduced fatigue, and strong effects on improving focus, concentration, and motivation to exercise. The purpose of this study was to examine the safety and non-habituating effects of TeaCrine®, a nature-identical, chemically equivalent bioactive version of theacrine. METHODS Sixty healthy men (mean ± SD age, height, weight: 22.9 ± 4.7 years, 183.5 ± 9.2 cm, 86.5 ± 13.7 kg) and women (22.3 ± 4.5 years, 165.2 ± 12.3 cm, 69.0 ± 17.4 kg) were placed into one of three groups: placebo (PLA, n = 20), 200 mg TeaCrine® (LD, n = 19) or 300 mg Teacrine® (HD, n = 21) and ingested their respective supplement once daily for 8 weeks. Primary outcomes were fasting clinical safety markers (heart rate, blood pressure, lipid profiles, hematologic blood counts, biomarkers of liver/kidney/immune function) and energy, focus, concentration, anxiety, motivation to exercise, and POMS measured prior to daily dosing to ascertain potential tachyphylactic responses and habituation effects. Data were analyzed via two-way (group × time) ANOVAs and statistical significance was accepted at p < 0.05. RESULTS All values for clinical safety markers fell within normal limits and no group × time interactions were noted. No evidence of habituation was noted as baseline values for energy, focus, concentration, anxiety, motivation to exercise, and POMS remained stable in all groups across the 8-week study protocol. CONCLUSIONS These findings support the clinical safety and non-habituating neuro-energetic effects of TeaCrine® supplementation over 8 weeks of daily use (up to 300 mg/day). Moreover, there was no evidence of a tachyphylactic response that is typical of neuroactive agents such as caffeine and other stimulants.
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Beneficial Effects of Pterocarpan-High Soybean Leaf Extract on Metabolic Syndrome in Overweight and Obese Korean Subjects: Randomized Controlled Trial.
Ryu, R, Jeong, TS, Kim, YJ, Choi, JY, Cho, SJ, Kwon, EY, Jung, UJ, Ji, HS, Shin, DH, Choi, MS
Nutrients. 2016;(11)
Abstract
Pterocarpans are known to have antifungal and anti-inflammatory properties. However, little is known about the changes in transcriptional profiles in response to a pterocarpan-high soybean leaf extract (PT). Therefore, this study investigated the effects of PT on blood glucose and lipid levels, as well as on the inflammation-related gene expression based on a peripheral blood mononuclear cells (PBMCs) mRNA sequencing analysis in Korean overweight and obese subjects with mild metabolic syndrome. The participants were randomly assigned to two groups and were administered either placebo (starch, 3 g/day) or PT (2 g/day) for 12 weeks. The PT intervention did not change body weight, body fat percentage and body mass index (BMI). However, PT significantly decreased the glycosylated hemoglobin (HbA1c), plasma glucose, free fatty acid, total cholesterol, and non-HDL cholesterol levels after 12 weeks. Furthermore, PT supplementation significantly lowered the homeostatic index of insulin resistance, as well as the plasma levels of inflammatory markers. Finally, the mRNA sequencing analysis revealed that PT downregulated genes related to immune responses. PT supplementation is beneficial for the improvement of metabolic syndrome by altering the fasting blood and plasma glucose, HbA1c, plasma lipid levels and inflammation-related gene expression in PBMCs.
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Cytokine response to dietary rehabilitation with curd (Indian dahi) & leaf protein concentrate in malnourished children.
Dewan, P, Kaur, IR, Faridi, MM, Agarwal, KN
The Indian journal of medical research. 2009;(1):31-6
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Abstract
BACKGROUND & OBJECTIVE Protein energy malnutrition (PEM), an important cause of secondary immune deficiency, is associated with several abnormalities in the immune system including cytokine production. In the present study cytokine levels (both pro- and anti-inflammatory) were evaluated in protein energy malnourished children following nutritional rehabilitation with curd (Indian dahi) and leaf protein concentrate (LPC). METHODS Eighty moderately and severely malnourished children, 1-5 yr of age, received the WHO recommended diet for severe malnutrition, modified according to local dietary habits, containing in addition either curd or micronutrient-rich leaf protein concentrate, for a period of 15 days. Cytokine levels [tumour necrosis factor alpha (TNFalpha), interferon gamma (IFNgamma), interleukin-10 (IL-10), interleukin-4 (IL-4)] were measured before and after dietary rehabilitation. RESULTS The baseline cytokine levels (TNFalpha, IFNgamma, IL-10 and IL-4) were high in malnourished children. Both the diets caused an increase in serum pro-inflammatory (TNFalpha, IFNgamma), and anti-inflammatory (IL-10) cytokine levels after nutritional rehabilitation. The increase in IL-10 was significant in children receiving curd. There was an insignificant fall in IL-4 levels with both the diets. The cytokine response was comparable in children with moderate and severe malnutrition, as also in children < 2 yr to those between 2-5 yr. INTERPRETATION & CONCLUSION The study suggests that cytokines (TNFalpha, IFNgamma, IL-10 and IL-4) may serve as biological markers to assess the effect of functional foods like curd or LPC on immunity in malnutrition. Curd may help to maintain the balance in cytokine production by increasing the production of IL-10, and may be considered in place of milk in the nutritional rehabilitation of malnourished children.
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Effect of purple sweet potato leaves consumption on the modulation of the immune response in basketball players during the training period.
Chang, WH, Chen, CM, Hu, SP, Kan, NW, Chiu, CC, Liu, JF
Asia Pacific journal of clinical nutrition. 2007;(4):609-15
Abstract
The aim of this study was to evaluate the effect of the consumption of purple sweet potato leaves (PSPLs) on the immune response and the modulation of that response in 15 basketball players during a training period. They completed the 7-week study consisted of a run-in period (week 1), a PSPLs diet (200 g PSPLs/d; weeks 2, 3), a washout period (weeks 4, 5), and a control diet (low polyphenols content and carotenoid content adjusted to the same level as that of PSPLs diet; weeks 6 and 7). Blood, urine, and saliva samples were collected for biochemical analysis. The results showed that the plasma polyphenols concentration increased significantly in the PSPLs period. Compared with the control period, the PSPLs consumption produced a significant increase in the proliferation responsiveness of peripheral blood mononuclear cells (PBMC), cytotoxic activity of nature killer (NK) cells, and secretion of interferon (IFN)-gamma. However, no significant increase in the secretion of salivary immunoglobulin A (sIgA), interleukin (IL)-2, or interleukin-4 was observed after PSPLs consumption. In conclusion, consumption of a PSPLs diet for 2 weeks can modulate the immune response of basketball players during a training period.