Neural Network-Based Clinical Prediction System for Identifying the Clinical Effects of Saffron (Crocus sativus L) Supplement Therapy on Allergic Asthma: Model Evaluation Study
JMIR MEDICAL INFORMATICS
Authors: Hosseini, Seyed Ahmad; Jamshidnezhad, Amir; Zilaee, Marzie; Dehaghi, Behzad Fouladi; Mohammadi, Abbas; Hosseini, Seyed Mohsen
Abstract
Background: Asthma is commonly associated with chronic airway inflammation and is the underlying cause of over a million deaths each year. Crocus sativus L, commonly known as saffron, when used in the form of traditional medicines, has demonstrated anti-inflammatory effects which may be beneficial to individuals with asthma. Objective: The objective of this study was to develop a clinical prediction system using an artificial neural network to detect the effects of C sativus L supplements on patients with allergic asthma. Methods: A genetic algorithm-modified neural network predictor system was developed to detect the level of effectiveness of C sativus L using features extracted from the clinical, immunologic, hematologic, and demographic information of patients with asthma The study included data from men (n=40) and women (n=40) individuals with mild or moderate allergic asthma from 18 to 65 years of age. The aim of the model was to estimate and predict the level of effect of C sativus L supplements on each asthma risk factor and to predict the level of alleviation in patients with asthma A genetic algorithm was used to extract input features for the clinical prediction system to improve its predictive performance. Moreover, an optimization model was developed for the artificial neural network component that classifies the patients with asthma using C sativus L supplement therapy. Results: The best overall performance of the clinical prediction system was an accuracy greater than 99% for training and testing data. The genetic algorithm-modified neural network predicted the level of effect with high accuracy for anti-heat shock protein (anti-HSP), high sensitivity C-reactive protein (hs-CRP), forced expiratory volume in the first second of expiration (FEV1), forced vital capacity (FVC), the ratio of FEV1/FVC, and forced expiratory flow (FEF25%-75%) for testing data (anti-HSP: 96.5%; hs-CRP: 98.9%; FEV1: 98.1%; FVC: 97.5%; FEV1/FVC ratio: 97%; and FEF25%-75%: 96.7%, respectively). Conclusions: The clinical prediction system developed in this study was effective in predicting the effect of C sativus L supplements on patients with allergic asthma This clinical prediction system may help clinicians to identify early on which clinical factors in asthma will improve over the course of treatment and, in doing so, help clinicians to develop effective treatment plans for patients with asthma.
Cell Stress Induced Stressome Release Including Damaged Membrane Vesicles and Extracellular HSP90 by Prostate Cancer Cells
CELLS
Authors: Eguchi, Takanori; Sogawa, Chiharu; Ono, Kisho; Matsumoto, Masaki; Manh Tien Tran; Okusha, Yuka; Lang, Benjamin J.; Okamoto, Kuniaki; Calderwood, Stuart K.
Abstract
Tumor cells exhibit therapeutic stress resistance-associated secretory phenotype involving extracellular vesicles (EVs) such as oncosomes and heat shock proteins (HSPs). Such a secretory phenotype occurs in response to cell stress and cancer therapeutics. HSPs are stress-responsive molecular chaperones promoting proper protein folding, while also being released from cells with EVs as well as a soluble form known as alarmins. We have here investigated the secretory phenotype of castration-resistant prostate cancer (CRPC) cells using proteome analysis. We have also examined the roles of the key co-chaperone CDC37 in the release of EV proteins including CD9 and epithelial-to-mesenchymal transition (EMT), a key event in tumor progression. EVs derived from CRPC cells promoted EMT in normal prostate epithelial cells. Some HSP family members and their potential receptor CD91/LRP1 were enriched at high levels in CRPC cell-derived EVs among over 700 other protein types found by mass spectrometry. The small EVs (30-200 nm in size) were released even in a non-heated condition from the prostate cancer cells, whereas the EMT-coupled release of EVs (200-500 nm) and damaged membrane vesicles with associated HSP90 alpha was increased after heat shock stress (HSS). GAPDH and lactate dehydrogenase, a marker of membrane leakage/damage, were also found in conditioned media upon HSS. During this stress response, the intracellular chaperone CDC37 was transcriptionally induced by heat shock factor 1 (HSF1), which activated the CDC37 core promoter, containing an interspecies conserved heat shock element. In contrast, knockdown of CDC37 decreased EMT-coupled release of CD9-containing vesicles. Triple siRNA targeting CDC37, HSP90 alpha, and HSP90 beta was required for efficient reduction of this chaperone trio and to reduce tumorigenicity of the CRPC cells in vivo. Taken together, we define "stressome" as cellular stress-induced all secretion products, including EVs (200-500 nm), membrane-damaged vesicles and remnants, and extracellular HSP90 and GAPDH. Our data also indicated that CDC37 is crucial for the release of vesicular proteins and tumor progression in prostate cancer.