Lawrence W. C. Chan

Modulating effect of SIRT1 activation induced by resveratrol on Foxo1-associated apoptotic signalling in senescent heart

Cardiac function is impaired and Foxo1/Bim‐related apoptotic signalling is up‐regulated in senescent heart Activation of SIRT1 deacetylase activity by resveratrol attenuates the Foxo1/Bim signalling axis in senescent heart

Acylated and unacylated ghrelin inhibit doxorubicin-induced apoptosis in skeletal muscle.

Doxorubicin, a potent chemotherapeutic drug, has been demonstrated previously as an inducer of apoptosis in muscle cells. Extensive induction of apoptosis may cause excessive loss of muscle cells and subsequent functional decline in skeletal muscle. This study examined the effects of acylated ghrelin, a potential agent for treating cancer cachexia, on inhibiting apoptotic signalling in doxorubicin‐treated skeletal muscle. Unacylated ghrelin, a form of ghrelin that does not bind to GHSR‐1a, is also employed in this study to examine the GHSR‐1a signalling dependency of the effects of ghrelin.

A Mobile Phone Integrated Health Care Delivery System of Medical Images

With the growing computing capability of mobile phones, a handy mobile controller is developed for accessing the picture archiving and communication system (PACS) to enhance image management for clinicians with nearly no restriction in time and location using various wireless communication modes. The PACS is an integrated system for the distribution and archival of medical images that are acquired by different imaging modalities such as CT (computed tomography) scanners, CR (computed radiography) units, DR (digital radiography) units, US (ultrasonography) scanners, and MR (magnetic resonance) scanners. The mobile controller allows image management of the PACS including display, worklisting, query and retrieval of medical images in DICOM format. In this mobile system, a server program is developed in a PACS Web server which serves as an interface for client programs in the mobile phone and the enterprise PACS for image distribution in hospitals. The application processing is performed on the server side to reduce computational loading in the mobile device. The communication method of mobile phones can be adapted to multiple wireless environments in Hong Kong. This allows greater feasibility to accommodate the rapidly changing communication technology. No complicated computer hardware or software is necessary. Using a mobile phone embedded with the mobile controller client program, this system would serve as a tool for heath care and medical professionals to improve the efficiency of the health care services by speedy delivery of image information. This is particularly important in case of urgent consultation, and it allows health care workers better use of the time for patient care.

Autophagic adaptation is associated with exercise‐induced fibre‐type shifting in skeletal muscle

Acute exercise is known to activate autophagy in skeletal muscle. However, little is known about how basal autophagy in skeletal muscle adapts to chronic exercise. In the current study we aim to, firstly, examine whether long‐term habitual exercise alters the basal autophagic signalling in plantaris muscle and, secondly, examine the association between autophagy and fibre‐type shifting.

Disease-Specific Target Gene Expression Profiling of Molecular Imaging Probes: Database Development and Clinical Validation

Molecular imaging probes can target abnormal gene expression patterns in patients and allow early diagnosis of disease. For selecting a suitable imaging probe, the current Molecular Imaging and Contrast Agent Database (MICAD) provides descriptive and qualitative information on imaging probe characteristics and properties. However, MICAD does not support linkage with the expression profiles of target genes. The proposed Disease-specific Imaging Probe Profiling (DIPP) database quantitatively archives and presents the gene expression profiles of targets across different diseases, anatomic regions, and subcellular locations, providing an objective reference for selecting imaging probes. The DIPP database was validated with a clinical positron emission tomography (PET) study on lung cancer and an in vitro study on neuroendocrine cancer. The retrieved records show that choline kinase beta and glucose transporters were positively and significantly associated with lung cancer among the targets of 11C-choline and [18F]fluoro-2-deoxy-2-d-glucose (FDG), respectively. Their significant overexpressions corresponded to the findings that the uptake rate of FDG increased with tumor size but that of 11C-choline remained constant. Validated with the in vitro study, the expression profiles of disease-associated targets can indicate the eligibility of patients for clinical trials of the treatment probe. A Web search tool of the DIPP database is available at http://www.polyu.edu.hk/bmi/dipp/.Molecular imaging probes can target abnormal gene expression patterns in patients and allow early diagnosis of disease. For selecting a suitable imaging probe, the current Molecular Imaging and Contrast Agent Database (MICAD) provides descriptive and qualitative information on imaging probe characteristics and properties. However, MICAD does not support linkage with the expression profiles of target genes. The proposed Disease-specific Imaging Probe Profiling (DIPP) database quantitatively archives and presents the gene expression profiles of targets across different diseases, anatomic regions, and subcellular locations, providing an objective reference for selecting imaging probes. The DIPP database was validated with a clinical positron emission tomography (PET) study on lung cancer and an in vitro study on neuroendocrine cancer. The retrieved records show that choline kinase beta and glucose transporters were positively and significantly associated with lung cancer among the targets of 11C-choline and [18F]fluoro-2- deoxy-2-D-glucose (FDG), respectively. Their significant overexpressions corresponded to the findings that the uptake rate of FDG increased with tumor size but that of 11C-choline remained constant. Validated with the in vitro study, the expression profiles of disease-associated targets can indicate the eligibility of patients for clinical trials of the treatment probe. A Web search tool of the DIPP database is available at http://www.polyu.edu.hk/bmi/dipp/.

Resveratrol protects against doxorubicin-induced cardiotoxicity in aged hearts through the SIRT1-USP7 axis

Doxorubicin induced functional deteriorations and elevations of USP7‐related apoptotic/catabolic signalling in the senescent heart Resveratrol protects against doxorubicin‐induced alterations through the restoration of SIRT1 deacetylase activity

The Effect of Diabetes Self-Management Education on Body Weight, Glycemic Control, and Other Metabolic Markers in Patients with Type 2 Diabetes Mellitus

Aims. To comprehensively evaluate the effect of a short-term diabetes self-management education (DSME) on metabolic markers and atherosclerotic parameters in patients with type 2 diabetes. Methods. 76 patients with type 2 diabetes were recruited in this study. They were divided into the intervention group (n = 36) and control group (n = 40). The patients in the intervention group received a 3-month intervention, including an 8-week education on self-management of diabetes mellitus and subsequent 4 weeks of practice of the self-management guidelines. The patients in the control group received standard advice on medical nutrition therapy. Metabolic markers, carotid intima-media thickness (CIMT), and carotid arterial stiffness (CAS) of the patients in both groups were assessed before and after the 3-month intervention. Results. There was a significant reduction in hemoglobin A1c (HbA1c, −0.2 ± 0.56% versus 0.08 ± 0.741%; P < 0.05) and body weight (−1.19 ± 1.39 kg versus −0.61 ± 2.04 kg; P < 0.05) in the intervention group as compared to the control group. However, no significant improvements were found in other metabolic markers, CIMT and CAS (P > 0.05). Conclusions. DSME can improve HbA1c and body weight in patients with type 2 diabetes.

MiR-30a-5p Overexpression May Overcome EGFR-Inhibitor Resistance through Regulating PI3K/AKT Signaling Pathway in Non-small Cell Lung Cancer Cell Lines

Lung cancer is one of the most common deadly diseases worldwide, most of which is non-small cell lung cancer (NSCLC). The epidermal growth factor receptor (EGFR) mutant NSCLCs frequently respond to the EGFR tyrosine kinase inhibitors (EGFR-TKIs) treatment, such as Gefitinib and Erlotinib, but the development of acquired resistance limits the utility. Multiple resistance mechanisms have been explored, e.g., the activation of alternative tyrosine kinase receptors (TKRs) sharing similar downstream pathways to EGFR. MicroRNAs (miRNAs) are short, endogenous and non-coding RNA molecules, regulating the target gene expression. In this study, we explored the potential of miR-30a-5p in targeting the EGFR and insulin-like growth factor receptor-1 (IGF-1R) signaling pathways to overcome the drug resistance. IGF-1R is one of the tyrosine kinase receptors that share the same EGFR downstream molecules, including phosphatidylinositol 3 kinase (PI3K) and protein kinase B (AKT). In this work, an in vitro study was designed using EGFR inhibitor (Gefitinib), IGF-1R inhibitor (NVP-AEW541), and miRNA mimics in two Gefitinib-resistant NSCLC cell lines, H460 and H1975. We found that the combination of EGFR and IGF-1R inhibitors significantly decreased the phosphorylated AKT (p-AKT) expression levels compared to the control group in these two cell lines. Knockdown of phosphoinositide-3-kinase regulatory subunit 2 (PIK3R2) had the same effect with the dual inhibition of EGFR and IGF-1R to reduce the expression of p-AKT in the signaling pathway. Overexpression of miR-30a-5p significantly reduced the expression of the PI3K regulatory subunit (PIK3R2) to further induce cell apoptosis, and inhibit cell invasion and migration properties. Hence, miR-30a-5p may play vital roles in overcoming the acquired resistance to EGFR-TKIs, and provide useful information for establishing novel cancer treatment.

A SNOMED supported ontological vector model for subclinical disorder detection using EHR similarity

Electronic Health Records (EHR) form a valuable resource in the healthcare enterprise because clinical evidence can be provided to identify potential complications and support decisions on early intervention. Simple string matching, the common search algorithm, is not able to map a query to the similar health records in the database with respect to the medical concepts. A novel ontological vector model supported by the Systematized Nomenclature of Medicine Clinical Terms (SNOMED-CT) is proposed in this paper to project the disease terms of a health record to a feature space so that each health record can be characterized using a feature vector, giving a fingerprint of the record. The similarity between the query and database health records was measured by similarity measures of their feature vectors and string matching score respectively. Three types of similarity measures were considered in this study, namely, Euclidean distance (ED), direction cosine (DC) and modified direction cosine (mDC). Medical history and carotid ultrasonic imaging findings were collected from 47 subjects in Hong Kong. The dataset formed 1081 pairs of health records and ROC analysis was used to evaluate and compare the accuracy of the ontological vector model and simple string matching against the agreement of the presence or absence of carotid plaques identified by carotid ultrasound between two subjects. It was found that the score generated by simple string matching was a random rater but the ontological vector model was not. In other words, the degree of health record similarity based on the ontological vector model is associated with the agreement of atherosclerosis between two patients. The vector model using feature terms at the SNOMED-CT level 4 gave the best performance. The performance of mDC was very close to that of ED and DC but the properties of mDC make it more suitable for the retrieval of similar health records. It was also shown that the ontological vector model was enhanced by the support vector classifier approach.

Cumulative effects of hypertension, dyslipidemia, and chronic kidney disease on carotid atherosclerosis in Chinese patients with type 2 diabetes mellitus.

Aims. The aim of this study is to determine the extent of carotid atherosclerosis in Chinese patients with type 2 diabetes in relation to the cumulative atherosclerosis risk factors using ultrasonography. Methods. The presence of hypertension, dyslipidemia, and chronic kidney disease (CKD) was documented in 106 Chinese subjects with type 2 diabetes. Subjects with 0, 1, and ≥2 additional atherosclerosis risk factors were assigned into groups 1, 2, and 3, respectively (n = 17, 49, and 40, resp.). Using ultrasound, the carotid arteries were assessed for the presence of carotid plaque, plaque score, intima-media thickness (IMT), and carotid arterial stiffness. Results. With the adjustment for age and gender, the presence of plaque and plaque score were significantly higher in groups with more atherosclerosis risk factors (P < 0.05). In addition, age > 60 years old (odds ratio = 2.75; 95% CI: 1.26–6.0) and the presence of hypertension (odds ratio = 2.48; 95% CI: 1.11–5.58), dyslipidemia (odds ratio = 2.41; 95% CI: 1.05–5.51), and CKD (odds ratio = 7.80; 95% CI: 1.46–41.72) could independently predict higher plaque score (P < 0.05). Conclusions. Hypertension, dyslipidemia, and CKD in Chinese patients with type 2 diabetes have cumulative effects on the burden of carotid plaque.