Association between food insecurity and risk of chronic diseases affecting the kidney in older Korean patients.

AIMS: This study aimed to examine the association between food insecurity and the prevalence of chronic diseases among older adults in South Korea and to compare the findings with data from the United States (US). MATERIALS AND METHODS: We analyzed data from the Korea National Health and Nutrition Examination Survey (KNHANES) V (2010 - 2012) and VI (2013 - 2015) and 4 years (2012 - 2015) of food security questionnaire data. The data of 46,189 National Health and Nutrition Examination Survey participants (1999 - 2016) were subjected to propensity score-matched (PSM) analysis. RESULTS: We included 7,914 individuals from the KNHANES. In the older group (age > 65 years), no differences were observed in the prevalence of hypertension, diabetes, chronic kidney disease (CKD), and metabolic syndrome across the income groups. Income, education, and food security had no impact on hypertension, diabetes, and CKD prevalence in the multivariate logistic analysis after PSM. CKD was not associated with food insecurity (odds ratio (OR), 1.26; 95% confidence interval (CI), 0.94 - 1.26) in the final model using the KNHANES data; however, the U.S. NHANES data showed that an increased risk of hypertension was associated with food insecurity (OR, 1.27; 95% CI, 1.04 - 1.55). CONCLUSION: As per the U.S. NHANES data, food insecurity was associated with a high prevalence of hypertension, while as per the South Korean KNHANES data, food insecurity was not found to be associated with CKD, indicating divergent relationships between food insecurity and chronic diseases in the two countries. Further research is needed to explore these differences.

Metformin Decreases 2-HG Production through the MYC-PHGDH Pathway in Suppressing Breast Cancer Cell Proliferation.

The biguanide drug metformin has been widely used for the treatment of type 2 diabetes, and there is evidence supporting the anticancer effect of metformin despite some controversy. Here, we report the growth inhibitory activity of metformin in the breast cancer (MCF-7) cells, both in vitro and in vivo, and the associated metabolic changes. In particular, a decrease in a well-known oncometabolite 2-hydroxyglutarate (2-HG) was discovered by a metabolomics approach. The decrease in 2-HG by metformin was accompanied by the reduction in histone methylation, consistent with the known tumorigenic mechanism of 2-HG. The relevance of 2-HG inhibition in breast cancer was also supported by a higher level of 2-HG in human breast cancer tissues. Genetic knockdown of PHGDH identified the PHGDH pathway as the producer of 2-HG in the MCF-7 cells that do not carry isocitrate dehydrogenase 1 and 2 (IDH1/IDH2) mutations, the conventional producer of 2-HG. We also showed that metformin's inhibitory effect on the PHGDH-2HG axis may occur through the regulation of the AMPK-MYC pathway. Overall, our results provide an explanation for the coherent pathway from complex I inhibition to epigenetic changes for metformin's anticancer effect.

Metabolomic analysis of percutaneous fine-needle aspiration specimens of thyroid nodules: Potential application for the preoperative diagnosis of thyroid cancer.

Thyroid nodules are a very common problem. Since malignant thyroid nodules should be treated surgically, preoperative diagnosis of thyroid cancer is very crucial. Cytopathologic analysis of percutaneous fine-needle aspiration (FNA) specimens is the current gold standard for diagnosing thyroid nodules. However, this method has led to high rates of inconclusive results. Metabolomics has emerged as a useful tool in medical fields and shown great potential in diagnosing various cancers. Here, we evaluated the potential of nuclear magnetic resonance (NMR) analysis of percutaneous FNA specimens for preoperative diagnosis of thyroid cancer. We analyzed metabolome of FNA samples of papillary thyroid carcinoma (n = 35) and benign follicular nodule (n = 69) using a proton NMR spectrometer. The metabolomic profiles showed a considerable discrimination between benign and malignant nodules. Receiver operating characteristic (ROC) curve analysis indicated that seven metabolites could serve as discriminators (area under ROC curve value, 0.64-0.85). These findings demonstrated that NMR analysis of percutaneous FNA specimens of thyroid nodules can be potentially useful in the accurate and rapid preoperative diagnosis of thyroid cancer.

Cancer metabolomics in basic science perspective.

As metabolomics investigates metabolic pathways with the focus on metabolites, it is a suitable approach to address the complex metabolic alteration in cancer. In addition, metabolic profiles are affected by environmental and post-natal changes, and therefore, directly measuring many metabolites may provide epigenetically relevant information in cancer. Despite much development in our understanding of cancer metabolism, focus is often directed to signaling or metabolic proteins that modulate the metabolite levels. In this review, we discuss the "metabolite-oriented view" on cancer metabolism. We cover how metabolomics research contributed to our current insights into the basic mechanism of metabolic alterations leading to cancer. Then, we discuss specific metabolites and related enzymatic pathways directly related with tumorigenesis. We particularly pay attention to how metabolites regulate signaling proteins and metabolic enzymes ultimately leading to cancer phenotypes. Finally, we address future prospects and challenges of metabolomics in cancer research.

A smartphone metabolomics platform and its application to the assessment of cisplatin-induced kidney toxicity.

The application of smartphones to medical devices has been gaining attention in addressing accessibility and cost issues in healthcare, and the detection of medically relevant compounds has been demonstrated using customized smartphone hardware and/or software. Metabolomics, a newly rising omics field, has also spawned many medical applications but requires highly sophisticated and expensive equipment. Here, we describe a portable smartphone platform, built with readily available and affordable materials, that can perform all of the critical aspects of metabolomics. Excluding the smartphone itself, the total materials for the platform were obtained at less than US $20. For spectral data acquisition, the system utilized visible light (400-700 nm) and a built-in camera. All of the data processing, statistical analysis, and final-visualization components necessary for decision making were implemented in the smartphone platform. The platform is generally applicable as long as the analytes absorb visible light. We provide a proof-of-concept example wherein the metabolomics platform was applied to the assessment of cisplatin-induced kidney toxicity in a rat model, correctly predicting 7 out of 8 test samples.

Minimally invasive plate osteosynthesis using a helical plate for metadiaphyseal complex fractures of the proximal humerus.

Minimally invasive plate osteosynthesis (MIPO) has been used for humeral shaft fractures, but concerns exist about soft tissue injuries. The purpose of this study was to report the surgical technique and clinical outcomes of MIPO using a helical plate for metadiaphyseal complex humeral shaft fractures. Twelve patients with acute displacement involving proximal and middle third humeral shaft fractures (AO type C) were treated using the MIPO technique with a helical plate. Fracture union, complications, and functional outcomes were evaluated using the Constant-Murley score and Mayo Elbow Performance Score (MEPS) at final follow-up. All fractures united at an average of 17.9 weeks. No major complications, such as neurovascular injury, infection, and nonunion, were observed. Mean Constant-Murley and MEPS scores at final follow-up were 88.6 and 97.9, respectively. A MIPO technique using a helical plate can be a useful surgical option for metadiaphyseal complex fractures of the humeral shaft.

Heteronuclear NMR as a 4-in-1 analytical platform for detecting modification-specific signatures of therapeutic insulin formulations.

Detecting possible modifications of therapeutic proteins is a critical element of the quality control of protein drugs. Typically, a number of techniques are used to evaluate different modifications of therapeutic protein formulations. Using heteronuclear NMR spectroscopy, we show that the difference between various insulin formulations can be detected "as is" with little pretreatment and quickly. As an application to the quality control of insulin formulations, the NMR approach was compared with four different analytical methods: with reverse phase high pressure liquid chromatography (HPLC) (for mutations), with size exclusion chromatography (for oligomerization), with electrophoresis (for denaturation), and with mass spectrometry (for deamidation). All of the results showed that this single NMR method can provide the specific signatures for each modification and information that is at least equivalent to that offered by the conventional analytical methods. Importantly, NMR could yield information at each amino acid residue level which no other technique provided. The suggested NMR method, then, can be considered to be a facile and effective means of evaluating therapeutic protein formulations in a multifaceted way.

Anti-wrinkle effect of bone morphogenetic protein receptor 1a-extracellular domain (BMPR1a-ECD).

Bone morphogenetic proteins (BMPs) have diverse and important roles in the proliferation and differentiation of adult stem cells in our tissues. Especially, BMPs are well known to be the main inducers of bone formation, by facilitating both proliferation and differentiation of bone stem cells. Interestingly, in skin stem cells, BMPs repress their proliferation but are indispensable for the proper differentiation into several lineages of skin cells. Here, we tested whether BMP antagonists have an effect on the prevention of wrinkle formation. For this study we used an in vivo wrinkle-induced mouse model. As a positive control, retinoic acid, one of the top anti-wrinkle effectors, showed a 44% improvement compared to the non-treated control. Surprisingly, bone morphogenetic protein receptor 1a extracellular domain (BMPR1a-ECD) exhibited an anti-wrinkle effect which was 6-fold greater than that of retinoic acid. Our results indicate that BMP antagonists will be good targets for skin or hair diseases.

Sungsanpin, a lasso peptide from a deep-sea streptomycete.

Sungsanpin (1), a new 15-amino-acid peptide, was discovered from a Streptomyces species isolated from deep-sea sediment collected off Jeju Island, Korea. The planar structure of 1 was determined by 1D and 2D NMR spectroscopy, mass spectrometry, and UV spectroscopy. The absolute configurations of the stereocenters in this compound were assigned by derivatizations of the hydrolysate of 1 with Marfey's reagents and 2,3,4,6-tetra-O-acetyl-ß-d-glucopyranosyl isothiocyanate, followed by LC-MS analysis. Careful analysis of the ROESY NMR spectrum and three-dimensional structure calculations revealed that sungsanpin possesses the features of a lasso peptide: eight amino acids (-Gly(1)-Phe-Gly-Ser-Lys-Pro-Ile-Asp(8)-) that form a cyclic peptide and seven amino acids (-Ser(9)-Phe-Gly-Leu-Ser-Trp-Leu(15)) that form a tail that loops through the ring. Sungsanpin is thus the first example of a lasso peptide isolated from a marine-derived microorganism. Sungsanpin displayed inhibitory activity in a cell invasion assay with the human lung cancer cell line A549.

Global dynamic conformational changes in the suppressor domain of IP3 receptor by stepwise binding of the two lobes of calmodulin.

The roles of calmodulin (CaM) have been key points of controversy in the regulation of inositol-1,4,5-trisphosphate receptor (IP(3)R). To address the issue, we studied the interaction between CaM and the suppressor domain of IP(3)R, a key allosteric regulatory domain. First, by means of a pulldown and a fluorescence titration experiment, we confirmed the interaction. Through subsequent NMR binding experiments, we observed dramatic peak disappearances of the suppressor domain on interaction with apo-CaM. The data indicated that apo-CaM induces large-scale dynamic conformational changes in the suppressor domain, involving partial unfolding and subdomain rearrangement. Analysis of the NMR data of CaM surprisingly revealed that its C lobe alone can cause such changes. Further binding experiments showed that calcium allows the free N lobe to bind to the suppressor domain, which induces extra conformational changes in both of the proteins. These results were also confirmed with CaM deletion mutants with either the N or C lobe. On the basis of this novel binding mechanism, we propose a model in which the partial unfolding of the suppressor domain by apo-CaM and the stepwise binding of the N lobe of CaM to the suppressor domain are important elements of calcium/CaM inhibition of IP(3)R. We believe that our working model encompasses previous regulation mechanisms of IP(3)R by calcium/CaM and provides new insights into the CaM-target interaction.

Design and implementation of a seamless and comprehensive integrated medical device interface system for outpatient electronic medical records in a general hospital.

PURPOSE: Implementing an efficient Electronic Medical Record (EMR) system is regarded as one of the key strategies for improving the quality of healthcare services. However, the system's interoperability between medical devices and the EMR is a big barrier to deploying the EMR system in an outpatient clinical setting. The purpose of this study is to design a framework for a seamless and comprehensively integrated medical device interface system, and to develop and implement a system for accelerating the deployment of the EMR system. METHODS: We designed and developed a framework that could transform data from medical devices into the relevant standards and then store them in the EMR. The framework is composed of 5 interfacing methods according to the types of medical devices utilized at an outpatient clinical setting, registered in Samsung Medical Center (SMC) database. The medical devices used for this study were devices that have microchips embedded or that came packaged with personal computers. The devices are completely integrated with the EMR based on SMC's long term IT strategies. RESULTS: First deployment of integrating 352 medical devices into the EMR took place in April, 2006, and it took about 48 months. By March, 2010, every medical device was interfaced with the EMR. About 66,000 medical examinations per month were performed taking up an average of 50GB of storage space. We surveyed users, mainly the technicians. Out of 73 that responded, 76% of the respondents replied that they were strongly satisfied or satisfied, 20% replied as being neutral and only 4% complained about the speed of the system, which was attributed to the slow speed of the old-fashioned medical devices and computers. CONCLUSION: The current implementation of the medical device interface system based on the SMC framework significantly streamlines the clinical workflow in a satisfactory manner.

Effects of redox potential and Ca2+ on the inositol 1,4,5-trisphosphate receptor L3-1 loop region: implications for receptor regulation.

Inositol 1,4,5-trisphosphate receptor (IP(3)R) is a major intracellular Ca(2+) channel, modulated by many factors in the cytosolic and lumenal compartments. Compared with cytosolic control, lumenal-side regulation has been much less studied, and some of its mechanistic aspects have been controversial. Of particular interest with regard to lumenal regulation are whether it involves direct interactions between IP(3)R and the regulators, and whether it involves conformational changes of the lumenal regions of IP(3)R. To understand these lumenal-side regulation mechanisms, we studied the effects of two important lumenal regulatory factors, the redox potential and Ca(2+), on the L3-1 lumenal loop region of IP(3)R. The redox potential exerted direct and significant effects on the conformation of the loop region. By sharp contrast, Ca(2+) showed little effect on the L3-1 conformation, suggesting that the regulation of Ca(2+) is indirect or involves other receptor regions. GSH/oxidized glutathione-mediated oxidation introduced a unique intramolecular disulfide bond between Cys(34) and Cys(42). A variety of NMR experiments revealed that oxidation also induces localized helical characteristics in the Cys(34)-Cys(42) region. Dynamics studies also showed reduced motions in the region upon oxidation, consistent with the conformational changes. The results raise the interesting possibility that Cys(34) and Cys(42) may act together as a reduction sensor, and that Cys(65) may function as an oxidation sensor. Overall, our studies suggest that the redox potential and Ca(2+) can regulate IP(3)R through totally different mechanisms: Ca(2+) by the indirect effect and the redox potential by direct action causing conformational changes.