A Systems Medicine Approach: Translating Emerging Science into Individualized Wellness.

In today's aging society, more people are living with lifestyle-related noncommunicable diseases (NCDs) such as cardiovascular disease, type 2 diabetes, obesity, and cancer. Numerous opinion-leader organizations recommend lifestyle medicine as the first-line approach in NCD prevention and treatment. However, there is a strong need for a personalized approach as "one-size-fits-all" public health recommendations have been insufficient in addressing the interindividual differences in the diverse populations. Advancement in systems biology and the "omics" technologies has allowed comprehensive analysis of how complex biological systems are impacted upon external perturbations (e.g., nutrition and exercise), and therefore is gradually pushing personalized lifestyle medicine toward reality. Clinicians and healthcare practitioners have a unique opportunity in advocating lifestyle medicine because patients see them as a reliable source of advice. However, there are still numerous technical and logistic challenges to overcome before personal "big data" can be translated into actionable and clinically relevant solutions. Clinicians are also facing various issues prior to bringing personalized lifestyle medicine to their practice. Nevertheless, emerging ground-breaking research projects have given us a glimpse of how systems thinking and computational methods may lead to personalized health advice. It is important that all stakeholders work together to create the needed paradigm shift in healthcare before the rising epidemic of NCDs overwhelm the society, the economy, and the dated health system.

META060 inhibits multiple kinases in the NF-kappaB pathway and suppresses LPS--mediated inflammation in vitro and ex vivo.

OBJECTIVE: We investigated whether a novel candidate META060 targeted the inflammatory signal transduction without affecting constitutive COX-2 enzymatic activity in lipopolysaccharide (LPS)-stimulated RAW 264.7 macrophages. We also investigated its bioavailability in humans and its anti-inflammatory effect ex vivo. METHODS: We measured prostaglandin E(2), nitric oxide, TNFalpha and IL-6 by ELISA, COX-2 protein by Western blot, NF-kappaB nuclear binding by electrophoretic mobility shift assays, and NF-kappaB activation by luciferase assay. Kinase inhibitions were measured by cell-free assays. Bioavailability was tested in 4 human subjects consuming 940 mg META060. LPS-activated TNFalpha and IL-6 were measured in peripheral blood mononuclear cells (PBMC) isolated from 1 subject up to 6 hours post administration. RESULTS: META060 dose-dependently inhibited prostaglandin E(2) and nitric oxide formation, COX-2 abundance, and NF-kappaB activation. In cell-free assays, META060 inhibited multiple kinases in the NF-kappaB signaling pathway, including BTK, PI3K, and GSK3. META060 was detected in the plasma of the subjects; isolated PBMC were resistant to LPS-stimulated TNFalpha and IL-6 production. CONCLUSION: Without inhibiting COX-2 enzyme, META060 reduces the inflammation by inhibiting multiple kinases involved in NF-kappaB pathway, and may have potential as a safe anti-inflammatory therapeutic.

Gastric mucosal cell model for estimating relative gastrointestinal toxicity of non-steroidal anti-inflammatory drugs.

The study objective was to characterize the AGS human gastric mucosal cell line as a model for estimating gastrointestinal toxicity of COX-inhibiting compounds. Rofecoxib, celecoxib, nimesulide, ibuprofen, indomethacin, aspirin, salicylic acid, naproxen and acetaminophen were tested for inhibition of COX-2-mediated prostaglandin E2 synthesis in A549 and AGS cells. The IC50 ratio AGS/A549 was calculated as an estimate of the therapeutic index (TI) for gastrointestinal toxicity. Calculated IC50 values of non-steroidal anti-inflammatory drugs (NSAIDs) in A549 cells were in excellent agreement with published values (r = 0.996; P < 0.005). Calcium ionophore induction of arachidonic acid release in AGS cells provided TI similar to those using platelets and A549 cells (r = 0.918; P < 0.01). The AGS/A549 model exhibited lower TI than the platelet/A549 model. Spearman ranking correlated clinical NSAID gastropathy with lower AGS TI values. The AGS cell line has excellent potential to serve as a model for assessing the gastrointestinal effects of COX-inhibiting compounds.

The use of complementary medicine for healthy aging.

By the year 2020, twenty percent of the US population will be aged 65 years or older. The greatest growth in numbers will be among those aged 85 years or older. If the healthcare demands of this group match those of their parents, it will place an extraordinary burden on funding for medical services. By promoting healthy aging, complementary medicine practitioners can improve the cost-effectiveness of healthcare delivery. A scientifically based complementary medicine program to promote healthy aging includes (1) diet and nutritional tailoring, (2) nutrient enhancement to meet specific individual needs, (3) exercise training, (4) stress management, (5) promotion of structural integrity, (6) environmental adjustment, (7) counseling on purposeful living, and (8) normalizing intercellular communication. The program described in this article incorporates these features and focuses on the following modifiable factors of unhealthy aging: altered mitochondrial function and oxidative stress, increased protein glycation, chronic inflammation, defects in methylation, reduced detoxification ability, and altered immunity.

Phytonutrition, phytotherapy, and phytopharmacology.

All families of plant food are known to contain phytonutrients, that is, unique substances produced during the natural course of plant growth and development that are specific to each plant's genes and environment. The term phytonutrition refers to the role of these substances in cultural food practices and cuisines worldwide in supporting health. In addition to their phytonutritive role, phytonutrients have a phytotherapeutic role, acting as modifiers of physiological function. The consumption of 30 to 50 mg per day of soy isoflavones in the traditional Japanese diet and the ability of this diet to help lower the incidence of breast cancer among Japanese women is an example of phytotherapeutic effect. The dividing line between phytonutrition and phytotherapy has blurred with the discovery that certain food components can not only modify physiological function but also aid in medical practices such as drug delivery. Naringenin, for example, the 4',5',7-hydroxyflavanone found exclusively in grapefruit, can slow hepatic detoxification of prescription drugs like cyclosporine and thus potentially help prevent rejection of transplanted organs. Natural and synthetic phytonutrients may differ significantly in their effect on physiological function owing to stereoisomeric composition. The potential of specific phytochemicals to promote health must be carefully evaluated with the same risk-benefit model traditionally used to assess concentrated levels of any substance placed into the body.

Psychoneuro-nutritional medicine: an advancing paradigm.

Recent research has led to the evolution of an important clinical relationship among psychology, neurobiochemistry, and nutrition. The result has been the development of the multidisciplinary field of psychoneuro-nutritional medicine. The successful application of this medical model to mental health problems ranging from behavior disorders in children to cognitive/emotional disorders in adults has opened the door to new lower-technology, cost-effective approaches to improving functional neurobiochemistry. This review describes the psychoneuro-nutritional medicine model and its application to a variety of biobehaviorally related health problems.

Evaluation and clinical significance of appendicular skeletal assessment by radiographic photodensitometry.

"Senile" or age-related bone loss affects cortical and trabecular bone and may be detected in the appendicular as well as the axial skeleton. This study presents radiographic photodensitometry as a precise and sensitive technique for evaluating appendicular skeletal status. Data from reproducibility studies indicate that the coefficient of variation for the technology is between 1.9% and 4.5% for the three bones analyzed. Evaluation of age-related changes in bone mass for over 800 subjects demonstrated a decline in mass vs. age after the fourth decade in women, with the slope of the decline being very similar to that seen in CT longitudinal studies. Applied serially to a patient over time, the technology identifies changes in bone mass and may be used to evaluate the response to intervention therapy.