Empirical Analysis of Body Constitution and Food Intake in Persons with Type 2 Diabetes from a TCM Perspective

This study examined the correlations between body constitution (BC) and food intake in a sample of persons with Type 2 Diabetes (T2DM) from a perspective of traditional Chinese medicine (TCM). Past research on BC of persons with diabetes (DM) from a TCM perspective revealed imbalanced state of Yin and Yang in terms of Yin-deficiency (YID), Yang-deficiency (YAD), and Yin-Yang-deficiency (YYD). However, no studies have attempted to find out if daily food intake has an influence on Yin-Yang balance. The present study adapted a mixed method, which constituted of two phases. Phase one involved an exploratory case study (n=18) conducted between May and June 2011 and phase two, a descriptive correlation study (n=210) between October and December 2013. Results showed that in phase-one, three cases showed YID and higher food intake in hot/warm nature, 12 cases with YAD and higher food intake in cold/cool nature while three cases with Yin-Yang-deficiency (YYD) and extremely high food intake in cold/cool nature. In phase-two, Spearman's correlation coefficient between food intake and YID presentations (YIDPs) (hot/warm food: rho=0.34, p=0.000; cold/cool food: rho= 0.18, p=0.006); YAD presentations (YADPs) (hot/warm food: rho=0.18, p=0.008; cold/cool food: rho=0.2, p=0.006); and YYD presentations (YYDPs) (hot/warm food: rho=0.29, p=0.006; cold/cool food: rho=0.2, p=0.003) have been noted. The findings concluded that persons with T2DM and YIDPs, YADPs, or YYDPs tend to have food intakes higher in hot/warm nature or cold/cool natur

Profiling of Substrate Specificities of 3C-Like Proteases from Group 1, 2a, 2b, and 3 Coronaviruses

BACKGROUND: Coronaviruses (CoVs) can be classified into alphacoronavirus (group 1), betacoronavirus (group 2), and gammacoronavirus (group 3) based on diversity of the protein sequences. Their 3C-like protease (3CL(pro)), which catalyzes the proteolytic processing of the polyproteins for viral replication, is a potential target for anti-coronaviral infection. METHODOLOGY/PRINCIPAL FINDINGS: Here, we profiled the substrate specificities of 3CL(pro) from human CoV NL63 (group 1), human CoV OC43 (group 2a), severe acute respiratory syndrome coronavirus (SARS-CoV) (group 2b) and infectious bronchitis virus (IBV) (group 3), by measuring their activity against a substrate library of 19 × 8 of variants with single substitutions at P5 to P3' positions. The results were correlated with structural properties like side chain volume, hydrophobicity, and secondary structure propensities of substituting residues. All 3CL(pro) prefer Gln at P1 position, Leu at P2 position, basic residues at P3 position, small hydrophobic residues at P4 position, and small residues at P1' and P2' positions. Despite 3CL(pro) from different groups of CoVs share many similarities in substrate specificities, differences in substrate specificities were observed at P4 positions, with IBV 3CL(pro) prefers P4-Pro and SARS-CoV 3CL(pro) prefers P4-Val. By combining the most favorable residues at P3 to P5 positions, we identified super-active substrate sequences 'VARLQ↓SGF' that can be cleaved efficiently by all 3CL(pro) with relative activity of 1.7 to 3.2, and 'VPRLQ↓SGF' that can be cleaved specifically by IBV 3CL(pro) with relative activity of 4.3. CONCLUSIONS/SIGNIFICANCE: The comprehensive substrate specificities of 3CL(pro) from each of the group 1, 2a, 2b, and 3 CoVs have been profiled in this study, which may provide insights into a rational design of broad-spectrum peptidomimetic inhibitors targeting the proteases

Profiling of Substrate Specificity of SARS-CoV 3CLpro

BACKGROUND: The 3C-like protease (3CL(pro)) of severe acute respiratory syndrome-coronavirus is required for autoprocessing of the polyprotein, and is a potential target for treating coronaviral infection. METHODOLOGY/PRINCIPAL FINDINGS: To obtain a thorough understanding of substrate specificity of the protease, a substrate library of 198 variants was created by performing saturation mutagenesis on the autocleavage sequence at P5 to P3' positions. The substrate sequences were inserted between cyan and yellow fluorescent proteins so that the cleavage rates were monitored by in vitro fluorescence resonance energy transfer. The relative cleavage rate for different substrate sequences was correlated with various structural properties. P5 and P3 positions prefer residues with high β-sheet propensity; P4 prefers small hydrophobic residues; P2 prefers hydrophobic residues without β-branch. Gln is the best residue at P1 position, but observable cleavage can be detected with His and Met substitutions. P1' position prefers small residues, while P2' and P3' positions have no strong preference on residue substitutions. Noteworthy, solvent exposed sites such as P5, P3 and P3' positions favour positively charged residues over negatively charged one, suggesting that electrostatic interactions may play a role in catalysis. A super-active substrate, which combined the preferred residues at P5 to P1 positions, was found to have 2.8 fold higher activity than the wild-type sequence. CONCLUSIONS/SIGNIFICANCE: Our results demonstrated a strong structure-activity relationship between the 3CL(pro) and its substrate. The substrate specificity profiled in this study may provide insights into a rational design of peptidomimetic inhibitors

Personalized Risk Assessment in Never, Light, and Heavy Smokers in a prospective cohort in Taiwan.

The objective of this study was to develop markedly improved risk prediction models for lung cancer using a prospective cohort of 395,875 participants in Taiwan. Discriminatory accuracy was measured by generation of receiver operator curves and estimation of area under the curve (AUC). In multivariate Cox regression analysis, age, gender, smoking pack-years, family history of lung cancer, personal cancer history, BMI, lung function test, and serum biomarkers such as carcinoembryonic antigen (CEA), bilirubin, alpha fetoprotein (AFP), and c-reactive protein (CRP) were identified and included in an integrative risk prediction model. The AUC in overall population was 0.851 (95% CI = 0.840-0.862), with never smokers 0.806 (95% CI = 0.790-0.819), light smokers 0.847 (95% CI = 0.824-0.871), and heavy smokers 0.732 (95% CI = 0.708-0.752). By integrating risk factors such as family history of lung cancer, CEA and AFP for light smokers, and lung function test (Maximum Mid-Expiratory Flow, MMEF25-75%), AFP and CEA for never smokers, light and never smokers with cancer risks as high as those within heavy smokers could be identified. The risk model for heavy smokers can allow us to stratify heavy smokers into subgroups with distinct risks, which, if applied to low-dose computed tomography (LDCT) screening, may greatly reduce false positives

Foreign language learning as potential treatment for mild cognitive impairment

As the number of older adults increases, age-related health issues (both physical and cognitive) and associated costs are expected to increase, placing emotional and financial stress on family members and the health system. Dementia is one of the most devastating and costly diseases that older adults face. The present study aimed to determine whether foreign language learning can improve cognitive outcomes of older adults with mild cognitive impairment (MCI). The objectives are to determine whether foreign language learning is (1) effective in boosting cognitive reserve and promoting healthy cognitive function and (2) superior to other established cognitively stimulating activities such as crossword and logic puzzles

The Enhanced metastatic potential of hepatocellular carcinoma (HCC) cells with sorafenib resistance

Acquired resistance towards sorafenib treatment was found in HCC patients, which results in poor prognosis. To investigate the enhanced metastatic potential of sorafenib resistance cells, sorafenib-resistant (SorR) cell lines were established by long-term exposure of the HCC cells to the maximum tolerated dose of sorafenib. Cell proliferation assay and qPCR of ABC transporter genes (ABCC1-3) were first performed to confirm the resistance of cells. Migration and invasion assays, and immunoblotting analysis on the expression of epithelial to mesenchymal transition (EMT) regulatory proteins were performed to study the metastatic potential of SorR cells. The expression of CD44 and CD133 were studied by flow cytometry and the gene expressions of pluripotency factors were studied by qPCR to demonstrate the enrichment of cancer stem cells (CSCs) in SorR cells. Control (CTL) and SorR cells were also injected orthotopically to the livers of NOD-SCID mice to investigate the development of lung metastasis. Increased expressions of ABCC1-3 were found in SorR cells. Enhanced migratory and invasive abilities of SorR cells were observed. The changes in expression of EMT regulatory proteins demonstrated an activation of the EMT process in SorR cells. Enriched proportion of CD44+ and CD44+CD133 + cells were also observed in SorR cells. All (8/8) mice injected with SorR cells demonstrated lung metastasis whereas only 1/8 mouse injected with CTL cells showed lung metastasis. HCC cells with sorafenib resistance demonstrated a higher metastatic potential, which may be due to the activated EMT process. Enriched CSCs were also demonstrated in the sorafenib resistant cells. This study suggests that advanced HCC patients with acquired sorafenib resistance may have enhanced tumor growth or distant metastasis, which raises the concern of long-term sorafenib treatment in advanced HCC patients who have developed resistance of sorafenib. © 2013 Chow et al.published_or_final_versio

rad21 Is Involved in Corneal Stroma Development by Regulating Neural Crest Migration

Previously, we identified RAD21(R450C) from a peripheral sclerocornea pedigree. Injection of this rad21 variant mRNA into Xenopus laevis embryos disrupted the organization of corneal stroma fibrils. To understand the mechanisms of RAD21-mediated corneal stroma defects, gene expression and chromosome conformation analysis were performed using cells from family members affected by peripheral sclerocornea. Both gene expression and chromosome conformation of cell adhesion genes were affected in cells carrying the heterozygous rad21 variant. Since cell migration is essential in early embryonic development and sclerocornea is a congenital disease, we studied neural crest migration during cornea development in X. laevis embryos. In X. laevis embryos injected with rad21 mutant mRNA, neural crest migration was disrupted, and the number of neural crest-derived periocular mesenchymes decreased significantly in the corneal stroma region. Our data indicate that the RAD21(R450C) variant contributes to peripheral sclerocornea by modifying chromosome conformation and gene expression, therefore disturbing neural crest cell migration, which suggests RAD21 plays a key role in corneal stroma development

Predicting late aortic complications after acute type A dissection surgery with volumetric measurements in a Singapore cohort

Introduction: This study was conducted to evaluate the efficacy of postoperative computed tomography (CT) measurements of aortic lumen volumes in predicting aortic-related complications following acute type A aortic dissection (ATAAD) repair. Methods: We conducted a single-institution retrospective aortic volumetric analysis of patients after ascending aorta replacement performed during 2001-2015. The volumetric measurements of total lumen (total-L), true lumen (TL), false lumen (FL), as well as the TL:FL ratio from the first and second postoperative computer angiograms were obtained. A generalised structural equation model was created to analyse the predictive utility of TL:FL ratio. Results: One hundred and twenty-five patients underwent surgical intervention, of whom 97 patients were eventually discharged and analysed for postoperative complications. A total of 19 patients were included in the final analysis. Patients with late postoperative aortic complications had a significantly higher FL volume and total-L volume on the first (FL volume P = 0.041, total-L volume P = 0.05) and second (FL volume P = 0.01, total-L volume P = 0.007) postoperative scans. The odds of having aortic complications were raised by 1% with a 1 cm3 increase in total-L volume and by 2% with a 1 cm3 increase in FL volume. The TL:FL ratio was significantly lower in patients who developed complications. Conclusion: Postoperative CT volumetric measurements in patients who developed complications are characterised by a significant increase in the FL volume and total-L volume from the first postoperative scans. Patients with disproportionately expanded FL presenting with TL:FL ratios less than 1 were associated with aortic complications. Hence, the TL:FL ratio may be a reliable and useful parameter to monitor postoperative disease progression and to evaluate the risk of late complications in ATAAD patients

Bone-targeting agents in major solid tumour metastases: a multinational cohort study

OBJECTIVE: To describe the epidemiology, clinical characteristics and utilisation patterns of bone-targeting agents (BTAs) in patients with bone metastases from breast, prostate and lung cancer. METHODS: This is a multinational retrospective cohort study including patients with three major solid tumours (breast, prostate and lung cancer) and newly initiated on BTAs (ie, denosumab, zoledronic acid and pamidronate). Records were retrieved from nationwide health databases from Hong Kong and Taiwan (HK and TW: 2013–2017) and Korea (KR: 2012–2016). Descriptive analyses included the annual incidence rates of bone metastases and the cumulative incidence curves of BTA initiation. We used Sankey diagrams to visualise the dynamic BTA utilisation patterns. RESULTS: The annual incidence rate of bone metastases ranged from 3.5% to 4.5% in TW, from 9.6% to 10.3% in HK and from 2.9% to 3.8% in KR. We identified 14.1% (5127), 9.3% (883) and 9.4% (4800) of patients with bone metastases newly initiated on BTAs in TW, HK and KR, respectively. The most frequently used BTA in TW (67.1%) and HK (51.9%) was denosumab, while in KR (84.8%) it was zoledronic acid. Sankey diagrams indicated the proportion of patients remaining on denosumab was highest in TW and HK, while it was zoledronic acid in KR. Specifically, in TW, patients who were on bisphosphonates or had discontinued treatment frequently switched to or reinitiated denosumab. CONCLUSIONS: We found the rate of BTA utilisation remained low across all sites and tumour types in recent years. The dynamic utilisation patterns of BTAs provide better understanding of the treatment landscape for future evaluation of associated outcomes of patients