ORCID Profile
0000-0001-8182-8579
Current Organisation
Monash University Central Clinical School
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Publisher: Research Square Platform LLC
Date: 08-06-2020
DOI: 10.21203/RS.3.RS-33310/V1
Abstract: Background : The emergence of carbapenem-resistant Enterobacteriaceae made the treatment difficult, which has become a major issue of public health. A sharp increase of carbapenem-resistance rate in Klebsiella pneumoniae was observed in a maternity and child health care hospital in Zunyi, China, in 2014.To investigate the cause and epidemiology of the carbapenem-resistant Klebsiella pneumoniae (CRKp) in the affected hospital. Methods : In 2015-2016, CRKp isolated from all the clinical s les were analyzed to identify the carbapenem-resistance genes. They were then fingerprinted in order to determine their genetic relationship. Clinical data such as usage of imipenem in 2012-2016 and the nosocomial infection surveillance data were analyzed Results : Thirty five isolates of CRKp out of 4328 various pathogens were obtained and bla NDM-1 was identified to be the most common resistant gene present in the CRKp isolates. The fingerprint analysis identified 15 major clusters of CRKp isolates. The bacteria with close proximity relationship tended to be from the same wards. However, a few CRKp isolates from different wards were found to be genetically highly related. The clinical data showed a significantly higher usage of carbapenems in 2012-2013, before the CRKp rate sharply increased in 2014. The nosocomial infection surveillance showed unexpected high rate of failures to meet the requirement of the hospital environment hygiene and hand hygiene in the neonatal ward. Conclusion : The increasing isolation rate of CRKp was associated with poorly regulated usage of carbapenems, impropriate medical practices and the poor hospital environmental hygiene and hand hygiene.
Publisher: Walter de Gruyter GmbH
Date: 06-2021
Abstract: Diabetes is a noncommunicable disease and arguably represents the greatest pandemic in human history. Diabetic kidney disease (DKD) is seen in both type 1 and type 2 diabetes and can be detected in up to 30–50% of diabetic subjects. DKD is a progressive chronic kidney disease (CKD) and is a leading cause of mortality and morbidity in patients with diabetes. Renal fibrosis and inflammation are the major pathological features of DKD. There are a large number of independent and overlapping profibrotic and pro-inflammatory pathways involved in the pathogenesis and progression of DKD. Among these pathways, the transforming growth factor-β (TGF-β) pathway plays a key pathological role by promoting fibrosis. Sirtuin-1 (SIRT1) is a protein deacetylase that has been shown to be renoprotective with an anti-inflammatory effect. It is postulated that a reduction in renal SIRT1 levels could play a key role in the pathogenesis of DKD and that restoration of SIRT1 will attenuate DKD. Cell ision autoantigen 1 (CDA1) synergistically enhances the profibrotic effect of TGF-β in DKD by regulating the expression of the TGF-β type I receptor (TβRI). CDA1 has also been found to be an inhibitor of SIRT1 in the DNA damage response. Indeed, targeting CDA1 in experimental DKD not only attenuates diabetes-associated renal fibrosis but also attenuates the expression of key pro-inflammatory genes such as tumor necrosis factor-α (TNF-α) and Monocyte Che moattractant Protein-1 (MCP-1). In conclusion, there is a large body of experimental data to support the view that targeting CDA1 is a superior approach to directly targeting TGF-β in DKD since it is not only safe but also efficacious in retarding both fibrosis and inflammation.
Publisher: Impact Journals, LLC
Date: 03-03-2021
Publisher: SAGE Publications
Date: 28-09-2015
Publisher: Informa UK Limited
Date: 21-02-2022
Publisher: Elsevier BV
Date: 2011
DOI: 10.1038/KI.2010.374
Abstract: Cell ision autoantigen 1 (CDA1) modulates cell proliferation and transforming growth factor-β (TGF-β) signaling in a number of cellular systems here we found that its levels were elevated in the kidneys of two animal models of diabetic renal disease. The localization of CDA1 to tubular cells and podocytes in human kidney sections was similar to that seen in the rodent models. CDA1 small interfering RNA knockdown markedly attenuated, whereas its overexpression increased TGF-β signaling, modulating the expression of TGF-β, TGF-β receptors, connective tissue growth factor, collagen types I, III, IV, and fibronectin genes in HK-2 cells. CDA1 and TGF-β together were synergistic in stimulating TGF-β signaling and target gene expression. CDA1 knockdown effectively blocked TGF-β-stimulated expression of collagen genes. This was due to its ability to modulate the TGF-β type I, but not the type II, receptor, leading to increased phosphorylation of Smad3 and extracellular signal-regulated kinase mitogen-activated protein kinase. Furthermore, the Smad3 inhibitor, SIS3, markedly attenuated the activities of CDA1 in stimulating TGF-β signaling as well as gene expression of collagens I, III, and IV. Thus, our in vitro and in vivo findings show that CDA1 has a critical role in TGF-β signaling in the kidney.
Publisher: MDPI AG
Date: 10-08-2022
DOI: 10.3390/PATHOGENS11080902
Abstract: Aims: We investigate how fasting blood glucose (FBG) levels affect the clinical severity in coronavirus disease 2019 (COVID-19) patients, pneumonia patients with sole bacterial infection, and pneumonia patients with concurrent bacterial and fungal infections. Methods: We enrolled 2761 COVID-19 patients, 1686 pneumonia patients with bacterial infections, and 2035 pneumonia patients with concurrent infections. We used multivariate logistic regression analysis to assess the associations between FBG levels and clinical severity. Results: FBG levels in COVID-19 patients were significantly higher than in other pneumonia patients during hospitalisation and at discharge (all p 0.05). Among COVID-19 patients, the odds ratios of acute respiratory distress syndrome (ARDS), respiratory failure (RF), acute hepatitis/liver failure (AH/LF), length of stay, and intensive care unit (ICU) admission were 12.80 (95% CI, 4.80–37.96), 5.72 (2.95–11.06), 2.60 (1.20–5.32), 1.42 (1.26–1.59), and 5.16 (3.26–8.17) times higher in the FBG ≥7.0 mmol/L group than in FBG 6.1 mmol/L group, respectively. The odds ratios of RF, AH/LF, length of stay, and ICU admission were increased to a lesser extent in pneumonia patients with sole bacterial infection (3.70 [2.21–6.29] 1.56 [1.17–2.07] 0.98 [0.88–1.11] 2.06 [1.26–3.36], respectively). The odds ratios of ARDS, RF, AH/LF, length of stay, and ICU admission were increased to a lesser extent in pneumonia patients with concurrent infections (3.04 [0.36–6.41] 2.31 [1.76–3.05] 1.21 [0.97–1.52] 1.02 [0.93–1.13] 1.72 [1.19–2.50], respectively). Among COVID-19 patients, the incidence rate of ICU admission on day 21 in the FBG ≥ 7.0 mmol/L group was six times higher than in the FBG 6.1 mmol/L group (12.30% vs. 2.21%, p 0.001). Among other pneumonia patients, the incidence rate of ICU admission on day 21 was only two times higher. Conclusions: Elevated FBG levels at admission predict subsequent clinical severity in all pneumonia patients regardless of the underlying pathogens, but COVID-19 patients are more sensitive to FBG levels, and suffer more severe clinical complications than other pneumonia patients.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 2021
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 10-09-2021
Publisher: MDPI AG
Date: 22-12-2022
DOI: 10.3390/JCM12010088
Abstract: Aims: To investigate whether renal pathology is an independent predictor for end-stage renal disease (ESRD) in diabetic kidney diseases (DKD) with nephrotic range proteinuria. Methods: A total of 199 DKD patients with nephrotic range proteinuria underwent renal biopsy and were ided into an ESRD group and a non-ESRD group. A Kaplan–Meier analysis was used to compare renal survival rate, and univariate and multivariate Cox proportional hazard analyses were used to determine the predictors of the ESRD. Results: The mean age of included patients was 51.49 ± 9.12 years and 113 patients (56.8%) progressed to ESRD. The median follow-up period was 16 (12–28) months. The glomerular pathology class III is the most common type (54.3%). In the Kaplan–Meier analysis, compared with patients without ESRD, patients with ESRD had a longer duration of diabetes (≥6 years), lower eGFR ( mL/min/1.73 m2), lower albumin ( g/L), lower hemoglobin ( g/L), and a higher grade of glomerular stage (class III + IV vs. class I + II) (p 0.05). The hemoglobin and e-GFR, but not the histopathological damage, were significantly associated with a higher risk of ESRD in both the univariate and multivariate Cox analyses. Conclusions: In patients with diabetic kidney disease characterized by nephrotic range proteinuria, histopathological damage (glomerular alterations, interstitial fibrosis and tubular atrophy (IFTA), interstitial inflammation, and arteriolar hyalinosis) is not associated with poor renal outcomes, but hemoglobin and e-GFR could predict poor renal outcomes.
Publisher: Bioscientifica
Date: 10-2021
DOI: 10.1530/EC-21-0307
Abstract: To investigate the relationship between serum uric acid (SUA) level and renal outcome in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). A total of 393 Chinese patients with T2DM and biopsy-proven DN and followed at least 1 year were enrolled in this study. Patients were stratified by the quartiles of baseline level of SUA: Q1 group: 286.02 ± 46.66 μmol/L ( n = 98) Q2 group: 358.23 ± 14.03 μmol/L ( n = 99) Q3 group: 405.50 ± 14.59 μmol/L ( n = 98) and Q4 group: 499.14 ± 56.97μmol/L ( n = 98). Renal outcome was defined by progression to end-stage renal disease (ESRD). Kaplan–Meier survival analysis and Cox proportional hazards model were used to analyze the association between SUA quartiles and the renal outcomes. During the median 3-year follow-up period, there were 173 ESRD outcome events (44.02%). No significant difference between SUA level and the risk of progression of DN ( P = 0.747) was shown in the Kaplan–Meier survival analysis. In multivariable-adjusted model, hazard ratios for developing ESRD were 1.364 (0.621–2.992 P = 0.439), 1.518 (0.768–3.002 P = 0.230) and 1.411 (0.706–2.821 P = 0.330) for the Q2, Q3 and Q4, respectively, in comparison with the Q1 ( P = 0.652). No significant association between SUA level and renal outcome of ESRD in Chinese patients with T2DM and DN was found in our study. Besides, the role of uric acid-lowering therapy in delaying DN progression and improving ESRD outcome had not yet been proven. Further study was needed to clarify the renal benefit of the uric acid-lowering therapy in the treatment of DN.
Publisher: Portland Press Ltd.
Date: 25-01-2019
DOI: 10.1042/CS20180438
Publisher: AME Publishing Company
Date: 04-2021
DOI: 10.21037/ATM-20-4550
Publisher: American Diabetes Association
Date: 23-03-2023
DOI: 10.2337/DC22-1943
Abstract: COVID-19 and diabetes both contribute to large global disease burdens. To quantify the prevalence of diabetes in various COVID-19 disease stages and calculate the population attributable fraction (PAF) of diabetes to COVID-19–related severity and mortality. Systematic review identified 729 studies with 29,874,938 COVID-19 patients. Studies detailed the prevalence of diabetes in subjects with known COVID-19 diagnosis and severity. Study information, COVID-19 disease stages, and diabetes prevalence were extracted. The pooled prevalence of diabetes in stratified COVID-19 groups was 14.7% (95% CI 12.5–16.9) among confirmed cases, 10.4% (7.6–13.6) among nonhospitalized cases, 21.4% (20.4–22.5) among hospitalized cases, 11.9% (10.2–13.7) among nonsevere cases, 28.9% (27.0–30.8) among severe cases, and 34.6% (32.8–36.5) among deceased in iduals, respectively. Multivariate metaregression analysis explained 53–83% heterogeneity of the pooled prevalence. Based on a modified version of the comparative risk assessment model, we estimated that the overall PAF of diabetes was 9.5% (7.3–11.7) for the presence of severe disease in COVID-19–infected in iduals and 16.8% (14.8–18.8) for COVID-19–related deaths. Subgroup analyses demonstrated that countries with high income levels, high health care access and quality index, and low diabetes disease burden had lower PAF of diabetes contributing to COVID-19 severity and death. Most studies had a high risk of bias. The prevalence of diabetes increases with COVID-19 severity, and diabetes accounts for 9.5% of severe COVID-19 cases and 16.8% of deaths, with disparities according to country income, health care access and quality index, and diabetes disease burden.
Publisher: Elsevier BV
Date: 04-2021
Publisher: Elsevier BV
Date: 05-2007
DOI: 10.1016/J.ORCP.2007.03.001
Abstract: To examine the relationship between family history of coronary heart disease (CHD), hypertension, and diabetes with risk of non-alcoholic fatty liver disease (NAFLD), and the possible interaction between these family histories and metabolic components for NAFLD. The 202 health office workers with no evidence of excessive alcohol drinking or hepatitis B or C virus infection were enrolled in the present study performed from March to June 2004. NAFLD was identified in 68 subjects by abdominal ultrasound. Logistic regression analysis showed that the presence of CHD family history increased the risk of NAFLD by 2.25-fold, 95% CI 1.1-4.1 (P = 0.014), while family history of diabetes or hypertension did not increase the risk. In combination with the presence of a family history of CHD, the effect on odds ratios (ORs) was increased for several metabolic features in predicting the incidence of NAFLD, including increased waist circumference, hypertriglyceridemia, hypertension and the occurrence of the metabolic syndrome. In a logistic regression model, the CHD family history enhances the summary predictive power of baseline clinical variables for NAFLD, but when the occurrence of increased waist circumference and hypertriglyceridemia are considered, the predictive value of a family history of CHD is no longer significant. This study has shown that the CHD family history may be clinically useful and associated with the occurrence of NAFLD, and that the likely link is through central obesity and the metabolic syndrome.
Publisher: American Society for Pharmacology & Experimental Therapeutics (ASPET)
Date: 16-03-2018
Abstract: A novel drug delivery system mediated by ultrasound (US) combined with microbubbles (MBs) (US+MB) could improve local drug concentration to enhance its efficacy. To investigate the influence of US+MB on methylprednisolone (MP), the effect of US+MB combined with MP (US+MB+MP) on lipopolysaccharide (LPS)-induced human mesangial cells (HMCs) and the underlying mechanism were explored in this study. The results revealed that HMCs treated with LPS underwent significant proliferation and exhibited an increase in nuclear transcription factor-
Publisher: The Endocrine Society
Date: 05-2003
Abstract: We searched expressed sequence tag databases with conserved domains of the short-chain alcohol dehydrogenase superfamily and identified another isoform of 17β-hydroxysteroid dehydrogenase, 17βHSDXI. This enzyme converts 5α-androstane-3α, 17β-diol to androsterone. The substrate has been implicated in supporting gestation and modulating γ-aminobutyric acid receptor activity. 17βHSDXI is colinear with human retinal short-chain dehydrogenase/reductase retSDR2, a protein with no known biological activity (accession no. AAF06939). Of the proteins with known function, 17βHSDXI is most closely related to the retinol-metabolizing enzyme retSDR1, with which it has 30% identity. There is a polymorphic stretch of 15 adenosines in the 5′ untranslated region of the cDNA sequence and a silent polymorphism at C719T. A 17βHSDXI construct with a stretch of 20 adenosines was found to produce significantly more enzyme activity than constructs containing 15 or less adenosines (43% vs. 26%, P & 0.005). The C719T polymorphism is present in 15% of genomic DNA s les. Northern blot analysis showed high levels of 17βHSDXI expression in the pancreas, kidney, liver, lung, adrenal, ovary, and heart. Immunohistochemical staining for 17βHSDXI is strong in steroidogenic cells such as syncytiotrophoblasts, sebaceous gland, Leydig cells, and granulosa cells of the dominant follicle and corpus luteum. In the adrenal 17βHSDXI, staining colocalized with the distribution of 17α-hydroxylase but was stronger in the mid to outer cortex. 17βHSDXI was also found in the fetus and increased after birth. Liver parenchymal cells and epithelium of the endometrium and small intestine also stained. Regulation studies in mouse Y1 cells showed that cAMP down-regulates 17βHSDXI enzymatic activity (40% vs. 32%, P & 0.05) and reduces gene expression to undetectable levels. All-trans-retinoic acid did not affect 17βHSDXI expression or activity, but addition of the retinoid together with cAMP significantly decreased activity over cAMP alone (32% vs. 23%, P & 0.05). Cloning and sequencing of the 17βHSDXI promoter identified the potential nuclear receptor steroidogenic factor-1 half-site TCCAAGGCCGG, and a cluster of three other potential steroidogenic factor-1 half-sites were found in the distal part of intron 1. Collectively, these results suggest a role for 17βHSDXI in androgen metabolism during steroidogenesis and a possible role in nonsteroidogenic tissues including paracrine modulation of 5α-androstane-3α, 17β-diol levels. 17βHSDXI could act by metabolizing compounds that stimulate steroid synthesis and/or by generating metabolites that inhibit it.
Publisher: Massachusetts Medical Society
Date: 20-08-2020
DOI: 10.1056/NEJMC2018688
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-2013
Publisher: American Diabetes Association
Date: 08-01-2018
DOI: 10.2337/DB17-0134
Abstract: Diabetes is a negative risk factor for aortic aneurysm, but the underlying explanation for this phenomenon is unknown. We have previously demonstrated that cell ision autoantigen 1 (CDA1), which enhances transforming growth factor-β signaling, is upregulated in diabetes. We hypothesized that CDA1 plays a key role in conferring the protective effect of diabetes against aortic aneurysms. Male wild-type, CDA1 knockout (KO), apolipoprotein E (ApoE) KO, and CDA1/ApoE double-KO (dKO) mice were rendered diabetic. Whereas aneurysms were not observed in diabetic ApoE KO and wild-type mice, 40% of diabetic dKO mice developed aortic aneurysms. These aneurysms were associated with attenuated aortic transforming growth factor-β signaling, reduced expression of various collagens, and increased aortic macrophage infiltration and matrix metalloproteinase 12 expression. In the well-characterized model of angiotensin II–induced aneurysm formation, concomitant diabetes reduced fatal aortic rupture and attenuated suprarenal aortic expansion, changes not seen in dKO mice. Furthermore, aortic CDA1 expression was downregulated ∼70% within biopsies from human abdominal aortic aneurysms. The identification that diabetes is associated with upregulation of vascular CDA1 and that CDA1 deletion in diabetic mice promotes aneurysm formation provides evidence that CDA1 plays a role in diabetes to reduce susceptibility to aneurysm formation.
Publisher: MDPI AG
Date: 30-09-2010
DOI: 10.3390/GENES1030335
Publisher: Elsevier BV
Date: 04-2007
Publisher: MDPI AG
Date: 14-12-2022
DOI: 10.3390/NU14245317
Abstract: The study aimed to compare the predictive value of the Circadian Syndrome (CircS) and Metabolic Syndrome (MetS) for cardiovascular disease (CVD). We used data of 12,156 adults aged ≥20 years who attended National Health and Nutrition Examination Survey (NHANES) 2005–2016. Mortality was obtained from the registry updated to 2019. The CircS was defined based on components of the MetS, in addition to short sleep and depression. Both the MetS and CircS were directly associated with self-reported history of CVD. The odds ratios for prevalent CVD associated with the CircS and MetS, respectively, were 2.92 (95% confidence interval (CI) 2.21–3.86) and 3.20 (2.38–4.30) in men, and 3.27 (2.34–4.59) and 3.04 (2.15–4.30) in women. The CircS had a better predictive power for prevalent CVD than that of MetS, as indicated by the higher positive predictive value (PPV) in men, the PPV for prevalent CVD with CircS was 23.1% and with MetS 20.9%, and in women these were 17.9% vs. 16.4%, respectively. However, the PPV of the CircS and MetS did not differ for the CVD mortality prediction. Women with CircS alone had a higher risk for both prevalent CVD and CVD mortality than those with MetS alone. In conclusion, the CircS is a significant and stronger predictor for CVD than the MetS in US adults.
Publisher: Springer Science and Business Media LLC
Date: 19-05-2022
DOI: 10.1007/S00125-022-05713-6
Abstract: The study aims to quantify the global trend of the disease burden of type 2 diabetes caused by various risks factors by country income tiers. Data on type 2 diabetes, including mortality and disability-adjusted life years (DALYs) during 1990–2019, were obtained from the Global Burden of Disease Study 2019. We analysed mortality and DALY rates and the population attributable fraction (PAF) in various risk factors of type 2 diabetes by country income tiers. Globally, the age-standardised death rate (ASDR) attributable to type 2 diabetes increased from 16.7 (15.7, 17.5)/100,000 person-years in 1990 to 18.5 (17.2, 19.7)/100,000 person-years in 2019. Similarly, age-standardised DALY rates increased from 628.3 (537.2, 730.9)/100,000 person-years to 801.5 (670.6, 954.4)/100,000 person-years during 1990–2019. Lower-middle-income countries reported the largest increase in the average annual growth of ASDR (1.3%) and an age-standardised DALY rate (1.6%) of type 2 diabetes. The key PAF attributing to type 2 diabetes deaths/DALYs was high BMI in countries of all income tiers. With the exception of BMI, while in low- and lower-middle-income countries, risk factors attributable to type 2 diabetes-related deaths and DALYs are mostly environment-related, the risk factors in high-income countries are mostly lifestyle-related. Type 2 diabetes disease burden increased globally, but low- and middle-income countries showed the highest growth rate. A high BMI level remained the key contributing factor in all income tiers, but environmental and lifestyle-related factors contributed differently across income tiers. To download the data used in these analyses, please visit the Global Health Data Exchange at bd-2019 .
Publisher: Springer Science and Business Media LLC
Date: 27-05-2021
DOI: 10.1007/S40618-021-01596-3
Abstract: To investigate the association between urinary complement proteins and renal outcome in biopsy-proven diabetic nephropathy (DN). Untargeted proteomic and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses and targeted proteomic analysis using parallel reaction-monitoring (PRM)-mass spectrometry was performed to determine the abundance of urinary complement proteins in healthy controls, type 2 diabetes mellitus (T2DM) patients, and patients with T2DM and biopsy-proven DN. The abundance of each urinary complement protein was in idually included in Cox proportional hazards models for predicting progression to end-stage renal disease (ESRD). Untargeted proteomic and functional analysis using the KEGG showed that differentially expressed urinary proteins were primarily associated with the complement and coagulation cascades. Subsequent urinary complement proteins quantification using PRM showed that urinary abundances of C3, C9, and complement factor H (CFAH) correlated negatively with annual estimated glomerular filtration rate (eGFR) decline, while urinary abundances of C5, decay-accelerating factor (DAF), and CD59 correlated positively with annual rate of eGFR decline. Furthermore, higher urinary abundance of CFAH and lower urinary abundance of DAF were independently associated with greater risk of progression to ESRD. Urinary abundance of CFAH and DAF had a larger area under the curve (AUC) than that of eGFR, proteinuria, or any pathological parameter. Moreover, the model that included CFAH or DAF had a larger AUC than that with only clinical or pathological parameters. Urinary abundance of complement proteins was significantly associated with ESRD in patients with T2DM and biopsy-proven DN, indicating that therapeutically targeting the complement pathway may alleviate progression of DN.
Publisher: Springer Science and Business Media LLC
Date: 13-11-2019
DOI: 10.1007/S00018-019-03354-4
Abstract: Glucokinase (GCK) is a key enzyme in glucose sensing and glycemic regulation. In humans, mutations in the GCK gene cause maturity-onset diabetes of the young 2 (MODY-2), a disease that is characterized by an early-onset and persistent hyperglycemia. It is known that Gck knockout (KO) is lethal in mice with Gck KO mice dying within 2 weeks after birth. Therefore, Gck KO mice are not suitable for preclinical study and have limited suitability to study the pathophysiological role of glucokinase in vivo. Here, we report the generation of a novel rabbit with a non-frameshift mutation of GCK gene (GCK-NFS) by cytoplasm microinjection of Cas9 mRNA and gRNA. These GCK-NFS rabbits showed typical features of MODY-2 including hyperglycemia and glucose intolerance with similar survival rate and weight compared to wild-type (WT) rabbits. The diabetic phenotype including pancreatic and renal dysfunction was also found in the F1-generation rabbits, indicating that the genetic modification is germline transmissible. Treatment of GCK-NFS rabbit with glimepiride successfully reduced the fasting blood glucose drastically and improved its islet function. In conclusion, this novel GCK mutant rabbit generated with the CRISPR/Cas9 system mimics most, if not all, histopathological and functional defects seen in MODY-2 patients such as hyperglycemia and will be a valuable rabbit model for preclinical studies and drug screening for diabetes as well as for studying the pathophysiological role of glucokinase.
Publisher: Japan Endocrine Society
Date: 2003
Publisher: Walter de Gruyter GmbH
Date: 09-2021
Publisher: Public Library of Science (PLoS)
Date: 16-07-2013
Publisher: Elsevier BV
Date: 04-2023
Publisher: Wiley
Date: 1997
Abstract: In the cloning and sequencing of growth-promoting genes of the blacklip abalone, Haliotis rubra (Leach, 1814), two DNA variable number of tandem repeats (VNTRs) were identified in abalone cDNA libraries. One contained a 33 bp repeat unit (5'-CCCAAGGTCCCCAAGGTCAGGGAGGCGAAGGCT-3') located in the 3' untranslated region of a putative growth hormone (GH) gene, and the repeat was designated as GHR. The other contained an 18 bp repeat unit (5'-ACCCGGCGCTTATTAGAG-3') located in the 3' untranslated region of a putative molluscan insulin-related peptides (MIP) gene, and was designated as MIPR. Primers flanking the two VNTR repeat regions were derived from sequence information. One hundred blacklip abalones were collected along the Victorian coastline and used in a preliminary population study. The range of GHR alleles containing the 33 bp basic unit repeat motif included 7 to 20 repeats, with allele GHR 8 not being identified. The most frequent alleles contained GHR 16 and 17 repeats (56.0% and 16.5%, respectively). Four types of alleles were identified in MIPR, viz 4, 5, 6 and 7 repeats. The alleles containing 6 and 5 repeats were the most frequent (50.0% and 41.5%, respectively). Overall, the results indicate that these two DNA minisatellites have use in abalone studies, including paternity resting, triploid testing, population genetic structure, and gene flow.
Publisher: Informa UK Limited
Date: 03-08-2022
DOI: 10.1080/14728222.2022.2133698
Abstract: Diabetic kidney disease (DKD) is the most common cause of end-stage renal disease (ESRD) worldwide. Currently, there is no effective treatment to completely prevent DKD progression to ESRD. Renal fibrosis and inflammation are the major pathological features of DKD, being pursued as potential therapeutic targets for DKD. Inflammation and renal fibrosis are involved in the pathogenesis of DKD. Anti-inflammatory drugs have been developed to combat DKD but without efficacy demonstrated. Thus, we have focused on the mechanisms of TGF-β-induced renal fibrosis in DKD, as well as discussing the important molecules influencing the TGF-β signaling pathway and their potential development into new pharmacotherapies, rather than targeting the ligand TGF-β and/or its receptors, such options include Smads, microRNAs, histone deacetylases, connective tissue growth factor, bone morphogenetic protein 7, hepatocyte growth factor, and cell ision autoantigen 1. TGF-β is a critical driver of renal fibrosis in DKD. Molecules that modulate TGF-β signaling rather than TGF-β itself are potentially superior targets to safely combat DKD. A comprehensive elucidation of the pathogenesis of DKD is important, which requires a better model system and access to clinical s les via collaboration between basic and clinical researchers.
Publisher: Elsevier BV
Date: 11-2000
Abstract: Trans-Golgi network (TGN) protein p230 is a peripheral membrane protein associated with the cytoplasmic face of the TGN. TGNp230 is an extensively coiled-coil protein with flexible amino- and carboxyl-terminal ends, associates with non-clathrin-coated vesicles arising from the TGN, and is implicated in vesicle biogenesis. Here we used an autoimmune serum from a patient with S ogren's syndrome to clone partial cDNAs from a human hepatoma HepG2 expression library. The partial cDNAs encoded a novel amino-terminal splice variant of TGNp230. Specific reactivity of the autoimmune serum for p230 is supported by immunofluorescene staining of the Golgi apparatus, immunoblotting of a > 200-kDa HeLa cell protein, and reactivity with a bacterially expressed GST-p230 fusion protein. The alternative splicing occurs within the first proline-rich domain of p230. It comprises a deletion of 30 bp followed immediately by an additional 66 bp absent in the published sequence. RT-PCR analysis indicated that the splicing occurs independently of previously reported carboxyl-terminal splicing, and that this novel splice variant is more frequent than the previously reported p230. The novel splice variant of p230 is also located at the TGN. We propose that p230 splice variants may be implicated in selection of cargo molecules for vesicles arising from the TGN.
Publisher: Elsevier BV
Date: 07-2023
Publisher: Frontiers Media SA
Date: 08-12-2021
DOI: 10.3389/FENDO.2021.791476
Abstract: We aimed to understand how glycaemic levels among COVID-19 patients impact their disease progression and clinical complications. We enrolled 2,366 COVID-19 patients from Huoshenshan hospital in Wuhan. We stratified the COVID-19 patients into four subgroups by current fasting blood glucose (FBG) levels and their awareness of prior diabetic status, including patients with FBG& .1mmol/L with no history of diabetes (group 1), patients with FBG& .1mmol/L with a history of diabetes diagnosed (group 2), patients with FBG≥6.1mmol/L with no history of diabetes (group 3) and patients with FBG≥6.1mmol/L with a history of diabetes diagnosed (group 4). A multivariate cause-specific Cox proportional hazard model was used to assess the associations between FBG levels or prior diabetic status and clinical adversities in COVID-19 patients. COVID-19 patients with higher FBG and unknown diabetes in the past (group 3) are more likely to progress to the severe or critical stage than patients in other groups (severe: 38.46% vs 23.46%-30.70% critical 7.69% vs 0.61%-3.96%). These patients also have the highest abnormal level of inflammatory parameters, complications, and clinical adversities among all four groups (all p& .05). On day 21 of hospitalisation, group 3 had a significantly higher risk of ICU admission [14.1% (9.6%-18.6%)] than group 4 [7.0% (3.7%-10.3%)], group 2 [4.0% (0.2%-7.8%)] and group 1 [2.1% (1.4%-2.8%)], (P& .001). Compared with group 1 who had low FBG, group 3 demonstrated 5 times higher risk of ICU admission events during hospitalisation (HR=5.38, 3.46-8.35, P& .001), while group 4, where the patients had high FBG and prior diabetes diagnosed, also showed a significantly higher risk (HR=1.99, 1.12-3.52, P=0.019), but to a much lesser extent than in group 3. Our study shows that COVID-19 patients with current high FBG levels but unaware of pre-existing diabetes, or possibly new onset diabetes as a result of COVID-19 infection, have a higher risk of more severe adverse outcomes than those aware of prior diagnosis of diabetes and those with low current FBG levels.
Publisher: Walter de Gruyter GmbH
Date: 09-2021
Publisher: Springer Science and Business Media LLC
Date: 19-01-2022
DOI: 10.1007/S11255-021-03051-X
Abstract: To investigate the prognostic value of metabolic syndrome (MetS) and its relationship with renal structure changes in patients with type 2 diabetes and associated diabetic nephropathy (DN). 411 Chinese patients with type 2 diabetes and biopsy-confirmed DN were enrolled in this retrospective study. MetS was defined according to the modified criteria of the 2005 International Diabetes Federation. Baseline demographics and clinical information at the time of renal biopsy were extracted from the hospital's electronic medical records system. Renal pathological findings were assessed according to Renal Pathology Society system. Univariate and multivariate logistic regression analyses were performed to define the pathological covariates associated with MetS. A competing risk model, with death as the competing risk, was used to estimate the sub-distribution hazard ratio (SHR) of MetS for end-stage kidney disease (ESKD). 224 (55%) patients had MetS. Patients with MetS had poor renal function and more severe interstitial fibrosis tubular atrophy scores (IFTA) than those without MetS. Multivariate logistic regression analysis revealed that IFTA was significantly associated with MetS (odds ratio per score increase 1.45, 95% confidence interval [CI] 1.02-2.05). Of the patients with DN at risk, 40% of patients progressed to ESKD. After adjusting for renal function and pathological parameters, the presence of MetS was an independent predictor for progression to ESKD (SHR 1.93, 95% CI 1.34-2.79). The SHRs for progression to ESKD also increased as the number of MetS components increased. Additionally, adding the IFTA scores improved the prognostic power of a model that only contained MetS and clinical covariates for predicting future ESKD. MetS is an independent prognostic predictor of ESKD in patients with T2D and DN, while adding the IFTA scores increased the prognostic value of MetS for renal outcome.
Publisher: American Diabetes Association
Date: 13-11-2018
DOI: 10.2337/DB18-0712
Abstract: Targeting cell ision autoantigen 1 (CDA1) is postulated to attenuate the profibrotic actions of transforming growth factor-β in diabetic nephropathy. This study has identified a regulatory protein for CDA1 and has then used genetic and pharmacological approaches to test in vivo whether strategies to target this pathway would lead to reduced renal injury. A novel protein, named CDA1BP1 (CDA1 binding protein 1), was identified as critical in regulating the profibrotic activity of CDA1. Genetic deletion of CDA1BP1 attenuated key parameters of renal fibrosis in diabetic mice. Furthermore, a series of short synthetic CDA1BP1 peptides competitively inhibited CDA1-CDA1BP1 binding in vitro with a hybrid peptide, CHA-050, containing a 12mer CDA1BP1 peptide and a previously known “cell-penetrating peptide,” dose-dependently reducing expression of collagens I and III in HK-2 cells. In vivo, a d–amino acid retro-inverso peptide, CHA-061, significantly attenuated diabetes-associated increases in the renal expression of genes involved in fibrotic and proinflammatory pathways. In a delayed intervention study, CHA-061 treatment reversed diabetes-associated molecular and pathological changes within the kidney. Specifically, CHA-061 significantly attenuated renal extracellular matrix accumulation and glomerular injury. Taken together, targeting the CDA1/CDA1BP1 axis is a safe, efficacious, and feasible approach to retard experimental diabetic nephropathy.
Publisher: MDPI AG
Date: 14-02-2023
DOI: 10.3390/IJMS24043857
Abstract: This study aimed to investigate the effect of the sympatholytic drug moxonidine on atherosclerosis. The effects of moxonidine on oxidised low-density lipoprotein (LDL) uptake, inflammatory gene expression and cellular migration were investigated in vitro in cultured vascular smooth muscle cells (VSMCs). The effect of moxonidine on atherosclerosis was measured by examining aortic arch Sudan IV staining and quantifying the intima-to-media ratio of the left common carotid artery in apolipoprotein E-deficient (ApoE−/−) mice infused with angiotensin II. The levels of circulating lipid hydroperoxides in mouse plasma were measured by ferrous oxidation-xylenol orange assay. Moxonidine administration increased oxidised LDL uptake by VSMCs via activation of α2 adrenoceptors. Moxonidine increased the expression of LDL receptors and the lipid efflux transporter ABCG1. Moxonidine inhibited mRNA expression of inflammatory genes and increased VSMC migration. Moxonidine administration to ApoE−/− mice (18 mg/kg/day) decreased atherosclerosis formation in the aortic arch and left common carotid artery, associated with increased plasma lipid hydroperoxide levels. In conclusion, moxonidine inhibited atherosclerosis in ApoE−/− mice, which was accompanied by an increase in oxidised LDL uptake by VSMCs, VSMC migration, ABCG1 expression in VSMCs and lipid hydroperoxide levels in the plasma.
Publisher: Springer Science and Business Media LLC
Date: 22-10-2010
DOI: 10.1007/S00125-009-1555-9
Abstract: Excess accumulation of vascular extracellular matrix (ECM) is an important pathological process in cardiovascular diseases including diabetes-associated atherosclerosis. We explored how a recently identified molecule, cell ision autoantigen 1 (CDA1), influences the profibrotic TGF-beta pathway leading to vascular ECM accumulation. Expression levels of genes encoding for CDA1, TGF-beta and connective tissue growth factor (CTGF) were examined in aorta from Apoe(-/-) mice with or without diabetes. We used retroviral and adenoviral constructs to knockdown or overexpress Tspyl2, the gene encoding CDA1, in mouse vascular smooth muscle cells (VSMCs) with or without TGF-beta treatment in order to demonstrate the role of CDA1 in TGF-beta signalling. In vivo studies indicated that the mRNA levels of CDA1-encoding gene Tspyl2 and protein levels of CDA1 were elevated in the aorta of diabetic Apoe(-/-) mice, accompanied by increased levels of Tgf-beta (also known as Tgfb1), Ctgf and ECM accumulation. In vitro studies in vascular cells showed that TGF-beta treatment rapidly increased CDA1 protein levels, which then lified TGF-beta signalling leading to upregulation of ECM genes. Knockdown of CDA1-encoding gene Tspyl2 to reduce cellular CDA1 level markedly attenuated TGF-beta-stimulated MAD homologue 3 (drosophila SMAD3) phosphorylation and transcriptional activities. CDA1 overproduction increased and Tspyl2 knockdown decreased expression of TGF-beta receptor type I, TbetarI (also known as Tgfbr1), but not TGF-beta receptor type II, TbetarII (also known as Tgfbr2), providing a mechanism for CDA1's action in modulating TGF-beta signalling. Knockdown of CDA1-encoding gene Tspyl2 also blocked the profibrotic effect of TGF-beta in VSMCs. CDA1 plays an important role in vascular ECM accumulation by lifying TGF-beta signalling. This is critical for the profibrotic effect of TGF-beta in the vasculature. CDA1 is therefore a potential target for attenuating vascular ECM accumulation caused by enhanced TGF-beta action, as seen in diabetic atherosclerosis.
Publisher: Elsevier BV
Date: 09-2001
Publisher: Informa UK Limited
Date: 04-04-2022
Publisher: Springer Science and Business Media LLC
Date: 26-05-2022
DOI: 10.1007/S44194-022-00006-X
Abstract: The pandemic of 2019 coronavirus (SARS-CoV-2) disease (COVID-19) has imposed a severe public health burden worldwide. Most patients with COVID-19 were mild. Severe patients progressed rapidly to critical condition including acute respiratory distress syndrome (ARDS), multi-organ failure and even death. This study aims to find early multi-organ injury indicators and blood glucose for predicting mortality of COVID-19. Fasting blood glucose (FBG) ≥7.0 mmol/L for two times during hospitalization and without a history of diabetes were defined as new-onset COVID-19-related diabetes (CRD). Indicators of injuries for multiple organs, including the lung, heart, kidney and liver, and glucose homeostasis were specifically analyzed for predicting death. A total of 120 patients with a severity equal to or greater than Moderate were hospitalized. After excluding patients with history of diabetes, chronic heart, kidney, and liver disease, 69 patients were included in the final analysis. Of the 69 patients, 23 were Moderate , 20 were Severe , and 26 were Critical (including 16 deceased patients). Univariable analysis indicated that CRD, lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), creatine kinase (CK) and creatinine (Cr) were associated with death. Multivariable analysis indicated that CRD was an independent predictor for death (HR = 3.75, 95% CI 1.26–11.15). Abnormal glucose homeostasis or CRD occurred earlier than other indicators for predicting poor outcomes. Indicators of multiple organ injury were in parallel with the expression patterns of ACE2 (the SARS-CoV-2 receptor) in different organs including pancreatic islet. New-onset COVID-19-related diabetes is an early indicator of multi-organ injury and predictor for poor outcomes and death in COVID-19 patients. As it is easy to perform for clinical practices and self-monitoring, glucose testing will be helpful for predicting poor outcomes to facilitate appropriate intensive care.
Publisher: Elsevier BV
Date: 02-2001
Publisher: Mary Ann Liebert Inc
Date: 12-2020
Publisher: Mary Ann Liebert Inc
Date: 04-2021
Publisher: Elsevier BV
Date: 04-2022
No related grants have been discovered for Zhonglin Chai.