Development and validation of the digestive function assessment instrument for traditional korean medicine: Sasang digestive function inventory

Objective. This study was conducted for development and validation of the Sasang Digestive Function Inventory (SDFI) with type-specific digestive function-related symptoms for identification of Sasang type and pathological pattern. Methods and Materials. We selected questionnaire items for pathophysiological symptoms using internal consistency analysis and examined construct validity using 193 healthy participants. Test-retest reliability with a four-week interval as well as convergent validity was examined using the Nepean Dyspepsia Index-Korean (NDIK), Functional Dyspepsia-Related Quality of Life (FDQOL), Dutch Eating Behavior Questionnaire (DEBQ), and Body Mass Index (BMI). Results. The 21-item SDFI showed satisfactory internal consistency (Cronbach’s alpha = 0.743) and test-retest reliability (, ). Three extracted subscales, SDFI-Digestion, SDFI-Appetite, and SDFI-Eating pattern, explained 56.02% of the total variance. The SDFI showed significant () correlation with total symptom score of NDIK, FDRQOL-Eating status, DEBQ-External Eating scale, and BMI. The SDFI score of the Tae-Eum () type was significantly () larger than that of the So-Eum () type. Conclusion. Current results demonstrated the reliability and validity of the SDFI and its subscales, which can be utilized as an objective instrument for diagnosis of Sasang types and assessment of the type-specific digestive function

Cationic Peptide Conjugated Poly(ethylene glycol) Diacrylate-based Hydrogel for Polynucleic Acid Delivery

Hydrogels, water-swollen polymeric networks, have been intensively investigated due to their unique characteristics that make them useful in biomedical and pharmaceutical applications. Hydrogels have been shown to be biocompatible and to possess similar hydration and flexibility to those of natural tissue. Hydrogels with well-defined physico-chemical properties may show a reproducible release profile when delivering bioactive molecules. However, prediction of the release profile of bioactive molecules is highly challenging when developing delivery systems that operate in a timely manner. In this presentation, to attempt to generate a predictable release model of polynucleic acid delivery systems, poly(ethylene glycol) diacrylate-based hydrogels were generated in nano-, micro-, and macrosized by electron-beam lithography, ultra-violet (UV) optical lithography, and UV polymerization followed by cutting with a biopsy punch, respectively. The generated hydrogel was conjugated with a peptide containing an octaarginine motif, known to have an ability to interact with polynucleic acids. Association/dissociation behaviors of the proposed system with polynucleic acids were explored using mathematical modeling. The results indicate that adsorption is multilayered, hydrogel surface is energetically heterogeneous, and electrostatic interaction occurs between them. Desorption profiles of polynucleic acids from the hydrogel suggest that there are two periods and rates of release that are presumably related to the state of the hydrogel. Understanding of interaction of polynucleic acids with the hydrogels provides beneficial information for hydrogel-based system design for polynucleic acid delivery in future. This work was conducted in a facility constructed with support from Research Facilities Improvement Program Grant Number C06 RR15482 and R01 NS055095 from NIH. The part of work was performed at the Argonne National Laboratory, Center for Nanoscale Materials, a U.S. Department of Energy, Office of Science, Office of Basic Energy Sciences User Facility under Contract No. DE-AC02-06CH11357

Kaboom! The Nano Bang Theory!

"My research has focused on creating hydrogel particles that are about 100 nanometers to 1 micrometer in size as a gene delivery vehicle to get genes to the site of disease. Hydrogel particles are comprised of an interconnected polymer network allowing them to carry and release genes in a controlled manner. The size and shape of vehicles are thought to be important to control the properties and characteristics of gene translocation into cells, but it is not clear which specific aspects are most important in design. To answer this question, I created hydrogel particles of controlled size and shape by electron beam lithography and ultra-violet optical lithography. Lithography techniques used to fabricate microchips enable us to generate hydrogel particles of controlled size and shape at this incredibly small size for biomedical applications. I am investigating that the geometry of these particles may influence translocation to and treatment of disease tissues, particularly arthritis. The presented image is of one micron cubic hydrogel particles on a silicon wafer created using an ultra-violet ray with each dot being a particle. The image is captured from Olympus MX61 reflective inverted microscope in dark field mode at Argonne National Laboratory – Center for Nanoscale Materials. Acknowledgement: The author would like to thank Drs. Derrick C. Mancini and Ralu Divan of Argonne National Laboratory for their generous support on the research. Use of the Center for Nanoscale Materials was supported by the U. S. Department of Energy, Office of Science, Office of Basic Energy Sciences, under Contract No. DE-AC02-06CH11357.

Caveolin-1 controls mitochondrial damage and ROS production by regulating fission - fusion dynamics and mitophagy.

As essential regulators of mitochondrial quality control, mitochondrial dynamics and mitophagy play key roles in maintenance of metabolic health and cellular homeostasis. Here we show that knockdown of the membrane-inserted scaffolding and structural protein caveolin-1 (Cav-1) and expression of tyrosine 14 phospho-defective Cav-1 mutant (Y14F), as opposed to phospho-mimicking Y14D, altered mitochondrial morphology, and increased mitochondrial matrix mixing, mitochondrial fusion and fission dynamics as well as mitophagy in MDA-MB-231 triple negative breast cancer cells. Further, we found that interaction of Cav-1 with mitochondrial fusion/fission machinery Mitofusin 2 (Mfn2) and Dynamin related protein 1 (Drp1) was enhanced by Y14D mutant indicating Cav-1 Y14 phosphorylation prevented Mfn2 and Drp1 translocation to mitochondria. Moreover, limiting mitochondrial recruitment of Mfn2 diminished formation of the PINK1/Mfn2/Parkin complex required for initiation of mitophagy resulting in accumulation of damaged mitochondria and ROS (mtROS). Thus, these studies indicate that phospho-Cav-1 may be an important switch mechanism in cancer cell survival which could lead to novel strategies for complementing cancer therapies

Pharmacogenomic landscape of patient-derived tumor cells informs precision oncology therapy.

Outcomes of anticancer therapy vary dramatically among patients due to diverse genetic and molecular backgrounds, highlighting extensive intertumoral heterogeneity. The fundamental tenet of precision oncology defines molecular characterization of tumors to guide optimal patient-tailored therapy. Towards this goal, we have established a compilation of pharmacological landscapes of 462 patient-derived tumor cells (PDCs) across 14 cancer types, together with genomic and transcriptomic profiling in 385 of these tumors. Compared with the traditional long-term cultured cancer cell line models, PDCs recapitulate the molecular properties and biology of the diseases more precisely. Here, we provide insights into dynamic pharmacogenomic associations, including molecular determinants that elicit therapeutic resistance to EGFR inhibitors, and the potential repurposing of ibrutinib (currently used in hematological malignancies) for EGFR-specific therapy in gliomas. Lastly, we present a potential implementation of PDC-derived drug sensitivities for the prediction of clinical response to targeted therapeutics using retrospective clinical studies