Milk Exosome-Glow Nanosystem for Cancer Cellular and Tissue Bioimaging.

Milk-derived exosomes are widely used for diagnosis, delivery, imaging, and theranostic applications. Near-Infrared (NIR) based fluorescence bioimaging is an attractive and safer technique that is used for clinical applications. However, almost all NIR imaging agents tend to have poor photostability, short half-life, nonspecific protein binding, and concentration-dependent aggregation(s).

One-step simultaneous liquid phase exfoliation-induced chirality in graphene and their chirality-mediated microRNA delivery.

Graphene (G) has established itself as an exciting prospect for a broad range of applications owing to its remarkable properties. Recent innovations in chiral nanosystems have led to sensors, drug delivery, catalysis, owing to the stereospecific interactions between various nanosystems and enantiomers. As the molecular structure of G itself is achiral introducing chirality in G by simple attachment of a functional group (a chiral ligand) on the G nanosheet may result in more diverse applications.

Indocyanine Green-based Glow Nanoparticles Probe for Cancer Imaging.

Indocyanine green (ICG) is one of the FDA-approved near infra-red fluorescent (NIRF) probes for cancer imaging and image-guided surgery in the clinical setting. However, the limitations of ICG include poor photostability, high concentration toxicity, short circulation time, and poor cancer cell specificity. To overcome these hurdles, we engineered a nanoconstruct composed of poly (vinyl pyrrolidone) (PVP)-indocyanine green that is cloaked self-assembled with tannic acid (termed as indocyanine green-based glow nanoparticles probe, ICG-Glow NPs) for the cancer cell/tissue-specific targeting.

Cardiopulmonary Imaging Utilization and Findings among Hospitalized COVID-19 Patients in Latin America: (From "RIMAC: Registry IMAging Cardiopulmonary among Hospitalized COVID-19 Patients in LATAM").

Objectives: Describe the use and findings of cardiopulmonary imaging-chest X-ray (cX-ray), echocardiography (cEcho), chest CT (cCT), lung ultrasound (LUS), and/or cardiac magnetic resonance imaging (cMRI)-in COVID-19 hospitalizations in Latin America (LATAM).

Background: There is a lack of information on the images used and their findings during the SARS-CoV-2 pandemic in LATAM.

Methods: Multicenter, prospective, observational study of COVID-19 inpatients, conducted from March to December 2020, from 12 high-complexity centers, in nine LATAM countries.

Gender differences in V˙O2 and HR kinetics at the onset of moderate and heavy exercise intensity in adolescents.

The majority of the studies on V˙O2 kinetics in pediatric populations investigated gender differences in prepubertal children during submaximal intensity exercise, but studies are lacking in adolescents. The purpose of this study was to test the hypothesis that gender differences exist in the V˙O2 and heart rate (HR) kinetic responses to moderate (M) and heavy (H) intensity exercise in adolescents. Twenty-one healthy African-American adolescents (9 males, 15.

Chronic hindlimb suspension unloading markedly decreases turnover rates of skeletal and cardiac muscle proteins and adipose tissue triglycerides.

We previously showed that a single bolus of "doubly-labeled" water ((2)H2 (18)O) can be used to simultaneously determine energy expenditure and turnover rates (synthesis and degradation) of tissue-specific lipids and proteins by modeling labeling patterns of protein-bound alanine and triglyceride-bound glycerol (Bederman IR, Dufner DA, Alexander JC, Previs SF. Am J Physiol Endocrinol Metab 290: E1048-E1056, 2006). Using this novel method, we quantified changes in the whole body and tissue-specific energy balance in a rat model of simulated "microgravity" induced by hindlimb suspension unloading (HSU).

Time course of hepatic gluconeogenesis during hindlimb suspension unloading.

The goal of this work was to determine the time-dependent changes in fractional hepatic gluconeogenesis (GNG) during conditions of hindlimb suspension unloading (HSU), a 'ground-based' method for inducing muscular atrophy to simulate space flight. We hypothesized that GNG would increase in HSU conditions as a result of metabolic shifts in the liver and skeletal muscle. A significant and progressive atrophy was observed in the soleus (30, 47 and 55%) and gastrocnemius muscles (0, 15 and 17%) after 3, 7 and 14 days of HSU, respectively.

VO(2) on-kinetics in isolated canine muscle in situ during slowed convective O(2) delivery.

The purpose of this study was to examine O(2) uptake (Vo(2)) on-kinetics when the spontaneous blood flow (and therefore O(2) delivery) on-response was slowed by 25 and 50 s. The isolated gastrocnemius muscle complex (GS) in situ was studied in six anesthetized dogs during transitions from rest to a submaximal metabolic rate (≈50-70% of peak Vo(2)). Four trials were performed: 1) a pretrial in which resting and steady-state blood flows were established, 2) a control trial in which the blood flow on-kinetics mean response time (MRT) was set at 20 s (CT20), 3) an experimental trial in which the blood flow on-kinetics MRT was set at 45 s (EX45), and 4) an experimental trial in which the blood flow on-kinetics MRT was set at 70 s (EX70).

Exercise intensity and oxygen uptake kinetics in African-American and Caucasian women.

The effect of exercise intensity on the on- and off-transient kinetics of oxygen uptake (VO(2)) was investigated in African American (AA) and Caucasian (C) women. African American (n = 7) and Caucasian (n = 6) women of similar age, body mass index and weight, performed an incremental test and bouts of square-wave exercise at moderate, heavy and very heavy intensities on a cycle ergometer. Gas exchange threshold (LT(GE)) was lower in AA (13.

Computational model of cellular metabolic dynamics: effect of insulin on glucose disposal in human skeletal muscle.

Identifying the mechanisms by which insulin regulates glucose metabolism in skeletal muscle is critical to understanding the etiology of insulin resistance and type 2 diabetes. Our knowledge of these mechanisms is limited by the difficulty of obtaining in vivo intracellular data. To quantitatively distinguish significant transport and metabolic mechanisms from limited experimental data, we developed a physiologically based, multiscale mathematical model of cellular metabolic dynamics in skeletal muscle.

Contraction-by-contraction VO2 and computer-controlled pump perfusion as novel techniques to study skeletal muscle metabolism in situ.

The purpose of this research was to develop new techniques to 1) rapidly sample venous O(2) saturation to determine contraction-by-contraction oxygen uptake (Vo(2)), and 2) precisely control the rate and pattern of blood flow adjustment from one chosen steady state to another. An indwelling inline oximeter probe connected to an Oximetrix 3 meter was used to sample venous oxygen concentration ([O(2)]) (via fractional saturation of Hb with O(2)). Data from the Oximetrix 3 were filtered, deconvolved, and processed by a moving average second by second.

Multiscale modeling of respiration.

In human studies investigating factors that control cellular respiration in working skeletal muscle, pulmonary VO dynamics (VO) measured at the mouth by indirect calorimetry is typically used to represent muscle O consumption (UO). Furthermore, measurement of muscle oxygenation using near-infrared spectroscopy has provided information on the dynamic balance between oxygen delivery and oxygen consumption at the microvascular level. To relate these measurements and gain quantitative understanding of the regulation of VO at the cellular, tissue and whole-body level, a multiscale computational model of oxygen transport and metabolism during exercise was developed.

Modeling oxygenation in venous blood and skeletal muscle in response to exercise using near-infrared spectroscopy.

Noninvasive, continuous measurements in vivo are commonly used to make inferences about mechanisms controlling internal and external respiration during exercise. In particular, the dynamic response of muscle oxygenation (Sm(O(2))) measured by near-infrared spectroscopy (NIRS) is assumed to be correlated to that of venous oxygen saturation (Sv(O(2))) measured invasively. However, there are situations where the dynamics of Sm(O(2)) and Sv(O(2)) do not follow the same pattern.

Non-invasive estimation of metabolic flux and blood flow in working muscle: effect of blood-tissue distribution.

Muscle oxygenation measurements by near infrared spectroscopy (NIRS) are frequently obtained in humans to make inferences about mechanisms of metabolic control of respiration in working skeletal muscle. However, these measurements have technical limitations that can mislead the evaluation of tissue processes. In particular, NIRS measurements of working muscle represent oxygenation of a mix of fibers with heterogeneous activation, perfusion and architecture.

Role of NADH/NAD+ transport activity and glycogen store on skeletal muscle energy metabolism during exercise: in silico studies.

Skeletal muscle can maintain ATP concentration constant during the transition from rest to exercise, whereas metabolic reaction rates may increase substantially. Among the key regulatory factors of skeletal muscle energy metabolism during exercise, the dynamics of cytosolic and mitochondrial NADH and NAD+ have not been characterized. To quantify these regulatory factors, we have developed a physiologically based computational model of skeletal muscle energy metabolism.

Metabolic dynamics in skeletal muscle during acute reduction in blood flow and oxygen supply to mitochondria: in-silico studies using a multi-scale, top-down integrated model.

Control mechanisms of cellular metabolism and energetics in skeletal muscle that may become evident in response to physiological stresses such as reduction in blood flow and oxygen supply to mitochondria can be quantitatively understood using a multi-scale computational model. The analysis of dynamic responses from such a model can provide insights into mechanisms of metabolic regulation that may not be evident from experimental studies. For the purpose, a physiologically-based, multi-scale computational model of skeletal muscle cellular metabolism and energetics was developed to describe dynamic responses of key chemical species and reaction fluxes to muscle ischemia.

Modeling of cellular metabolism and microcirculatory transport.

Oxygen and other substrates, waste products, hormone messengers, and cells and other particles of the immune system are all transported in a closed-loop circulatory system in vertebrates, within which pumped blood travels to within diffusion distances of practically every cell in the body. Exchange of oxygen and carbon dioxide in the pulmonary capillaries and absorption of nutrients in the gut provide the circulating blood with biochemical reactants to sustain bioenergetic processes throughout the body. Inputs and outputs transported by the microcirculation are necessary to drive the open-system nonequilibrium chemical reactions of metabolism that are essential for cellular function.

Role of the malate-aspartate shuttle on the metabolic response to myocardial ischemia.

The malate-aspartate (M-A) shuttle provides an important mechanism to regulate glycolysis and lactate metabolism in the heart by transferring reducing equivalents from cytosol into mitochondria. However, experimental characterization of the M-A shuttle has been incomplete because of limitations in quantifying cytosolic and mitochondrial metabolites. In this study, we developed a multi-compartment model of cardiac metabolism with detailed presentation of the M-A shuttle to quantitatively predict non-observable fluxes and metabolite concentrations under normal and ischemic conditions in vivo.

Modeling cellular metabolism and energetics in skeletal muscle: large-scale parameter estimation and sensitivity analysis.

Skeletal muscle plays a major role in the regulation of whole-body energy metabolism during physiological stresses such as ischemia, hypoxia, and exercise. Current experimental techniques provide relatively little in vivo data on dynamic responses of metabolite concentrations and metabolic fluxes in skeletal muscle to such physiological stimuli. As a complementary approach to experimental measurements and as a framework for quantitatively analyzing available in vivo data, a physiologically based model of skeletal muscle cellular metabolism and energetics is developed.

Multi-scale model of O2 transport and metabolism: response to exercise.

Regulation of pulmonary oxygen uptake (VO2p) during exercise depends on cellular energy demand, blood flow, ventilation, oxygen exchange across membranes, and oxygen utilization in the contracting skeletal muscle. In human and animal studies of metabolic processes that control cellular respiration in working skeletal muscle, pulmonary VO2 dynamics is measured at the mouth using indirect calorimetry. To provide information on the dynamic balance between oxygen delivery and oxygen consumption at the microvascular level, muscle oxygenation is measured using near-infrared spectroscopy.

The role of Ca2+ in coupling cardiac metabolism with regulation of contraction: in silico modeling.

The heart adapts the rate of mitochondrial ATP production to energy demand without noticeable changes in the concentration of ATP, ADP and Pi, even for large transitions between different workloads. We suggest that the changes in demand modulate the cytosolic Ca2+ concentration that changes mitochondrial Ca2+ to regulate ATP production. Thus, the rate of ATP production by the mitochondria is coupled to the rate of ATP consumption by the sarcomere cross-bridges (XBs).

Influence of exercise intensity on pulmonary oxygen uptake kinetics at the onset of exercise and recovery in male adolescents.

The dynamics of the pulmonary oxygen uptake (VO2) responses to square-wave changes in work rate can provide insight into bioenergetic processes sustaining and limiting exercise performance. The dynamic responses at the onset of exercise and during recovery have been investigated systematically and are well characterized at all intensities in adults; however, they have not been investigated completely in adolescents. We investigated whether adolescents display a slow component in their VO2 on- and off-kinetic responses to heavy- and very heavy-intensity exercise, as demonstrated in adults.

Muscle oxygen uptake differs from consumption dynamics during transients in exercise.

Relating external to internal respiration during exercise requires quantitative modeling analysis for reliable inferences with respect to metabolic rate. Often, oxygen transport and metabolism based on steady-state mass balances (Fick principle) and passive diffusion between blood and tissue are applied to link pulmonary to cellular respiration. Indeed, when the work rate does not change rapidly, a quasi-steady-state analysis based on the Fick principle is sufficient to estimate the rate of O2 consumption in working muscle.

Models of muscle contraction and energetics.

How does skeletal muscle manage to regulate the pathways of ATP synthesis during large-scale changes in work rate while maintaining metabolic homeostasis remains unknown. The classic model of metabolic regulation during muscle contraction states that accelerating ATP utilization leads to increasing concentrations of ADP and Pi, which serve as substrates for oxidative phosphorylation and thus accelerate ATP synthesis. An alternative model states that both the ATP demand and ATP supply pathways are simultaneously activated.