Recent advances in drug discovery for diabetic kidney disease

Introduction: Diabetic kidney disease (DKD) is a leading cause of end-stage renal disease (ESRD), and 40% of patients with diabetes develop DKD. Although some pathophysiological mechanisms and drug targets of DKD have been described, the effectiveness or clinical usefulness of such treatment has not been well validated. Therefore, searching for new targets and potential therapeutic candidates has become an emerging research area. Areas covered: The pathophysiological mechanisms, new drug targets and potential therapeutic compounds for DKD are addressed in this review. Expert opinion: Although preclinical and clinical evidence has shown some positive results for controlling DKD progression, treatment regimens have not been well developed to reduce the mortality in patients with DKD globally. Therefore, the discovery of new therapeutic targets and effective target-based drugs to achieve better and safe treatment are urgently required. Preclinical screening and clinical trials for such drugs are needed

ChIP-Array 2: integrating multiple omics data to construct gene regulatory networks

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ProteoMirExpress: inferring microRNA-centered regulatory networks from high-throughput proteomic and transcriptome data

MicroRNAs (miRNAs) regulate gene expression through translational repression and RNA degradation. Recently developed high-throughput proteomic methods measure gene expression changes at protein levels, and therefore can reveal the direct effects of miRNAs’ translational repression. Here, we present a web server, ProteoMirExpress that integrates proteomic and mRNA expression data together to infer miRNA-centered regulatory networks. With both high throughput data from the users, ProteoMirExpress is able to discover not only miRNA targets that have mRNA decreased, but also subgroups of targets whose proteins are suppressed but mRNAs are not significantly changed or whose mRNAs are decreased but proteins are not significantly changed, which were usually ignored by most current methods. Furthermore, both direct and indirect targets of miRNAs can be detected. Therefore ProteoMirExpress provides more comprehensive miRNA-centered regulatory networks. We use several published data to assess the quality of our inferred networks and prove the value of our server. ProteoMirExpress is available at http://jjwanglab.org/ProteoMirExpress, with free access to academic users.postprin

Dynamic Covalent Synthesis of Crystalline Porous Graphitic Frameworks

Porous graphitic framework (PGF) is a two-dimensional (2D) material that has emerging energy applications. An archetype contains stacked 2D layers, the structure of which features a fully annulated aromatic skeleton with embedded heteroatoms and periodic pores. Due to the lack of a rational approach in establishing in-plane order under mild synthetic conditions, the structural integrity of PGF has remained elusive and ultimately limited its material performance. Here, we report the discovery of the unusual dynamic character of the C=N bonds in the aromatic pyrazine ring system under basic aqueous conditions, which enables the successful synthesis of a crystalline porous nitrogenous graphitic framework with remarkable in-plane order, as evidenced by powder X-ray diffraction studies and direct visualization using high-resolution transmission electron microscopy. The crystalline framework displays superior performance as a cathode material for lithium-ion batteries, outperforming the amorphous counterparts in terms of capacity and cycle stability. Insertion of well-defined, evenly spaced nanoscale pores into the two-dimensional (2D) layers of graphene invokes exciting properties due to the modulation of its electronic band gaps and surface functionalities. A bottom-up synthesis approach to such porous graphitic frameworks (PGFs) is appealing but also remains a great challenge. The current methods of building covalent organic frameworks rely on a small collection of thermodynamically reversible reactions. Such reactions are, however, inadequate in generating a fully annulated aromatic skeleton in PGFs. With the discovery of dynamic pyrazine formation, we succeeded in applying this linking chemistry to obtain a crystalline PGF material, which has displayed high electrical conductivity and remarkable performance as a cathode material for lithium-ion batteries. We envision that the demonstrated success will open the door to a wide array of fully annulated 2D porous frameworks, which hold immense potential for clean energy applications. We report the unusual dynamic characteristics of the C=N bonds in the pyrazine ring promoted under basic aqueous conditions, which enables the successful synthesis of two-dimensional porous graphitic frameworks (PGFs) featuring fully annulated aromatic skeletons and periodic pores. The PGF displayed high electrical conductivity and remarkable performance as a cathode material for lithium-ion batteries, far outperforming the amorphous counterparts in terms of capacity and cycle stability

EpiRegNet: constructing epigenetic regulatory networks from high throughput gene expression data for humans

Poster Presentation: P-H010SUMMARY: EpiRegNet, an interactive web server, is able to construct an epigenetic regulatory network (ERN) from gene expression data, including microarray and RNA-seq data for human ESC, IMR90 and CD4+ T cells. Given a set of categorized genes, the system will find the epigenetic factors that contribute most to the differences in the gene expression and construct an ERN around these factors. Furthermore, the web server can demonstrate cooperative/competitive relationships among these factors in activating or repressing their target genes. Availability and Implementation: EpiRegNet is freely available on the web at http://wanglab.hku.hk/EpiRegNet/. It is implemented in perl, PHP and MySQL with all major browsers supported.postprintThe 2011 Hong Kong Inter-University Biochemistry Postgraduate Symposium, Hong Kong, 11 June 2011

Impact of air pollution on cognitive impairment in older people: A cohort study in rural and suburban China

© He et al. This is an accepted manuscript of a book chapter published by IOS Press. The definitive, peer reviewed and edited version of this Article is published in Calderón-Garcidueñas, L. (Ed.) Alzheimer’s Disease and Air Pollution, available online at: https://ebooks.iospress.nl/doi/10.3233/AIAD210021 The accepted version of the publication may differ from the final published version. For re-use please see the publisher's terms and conditions.Background: The impact of air pollution on cognitive impairment in older people has not been fully understood. It is unclear which air pollutants are the culprit. Objective: We assessed the associations of six air pollutants and air quality index (AQI) with cognitive impairment. Methods: We examined 7,311 participants aged ≥60 years from the ZJMPHS cohort in China. They were interviewed for baseline socio-demographic and disease risk factors in 2014, and re-interviewed in 2015 and 2016, respectively. The presence of cognitive impairment was determined by the Chinese version of the Mini-Mental State Examination. Daily area-level data monitored for air pollution during 2013-2015 was then examined for associations with cognitive impairment in logistic regression models. Results: Over the two years follow-up, 1,652 participants developed cognitive impairment, of which 917 were severe cases. Continuous air pollution data showed the risk of cognitive impairment increased with exposure to PM 2.5 (fully adjusted odds ratio [aOR] 1.04, 95%CI 1.01-1.08), PM 10 (1.03, 1.001-1.06), and SO 2 (1.04, 1.01-1.08), but not with NO 2, CO, O 3, and AQI. Categorized data analysis for low, middle, and high level exposure demonstrated that the aOR increased with PM 2.5 and AQI, somehow with PM 10 and CO, but not significantly with SO 2 and NO 2, and decreased with O 3. The patterns for these associations with severe cognitive impairment were stronger. Conclusion: Lowering PM 2.5, PM 10, SO 2, and CO level could reduce the risk of cognitive impairment in older Chinese. Strategies to target most important air pollutants should be an integral component of cognitive interventions.Published versio

Impact of air pollution on cognitive impairment in older people: A cohort study in rural and suburban China

This is an accepted manuscript of a paper published by IOS Press on 13/10/2020, available online at: https://content.iospress.com/articles/journal-of-alzheimers-disease/jad200587 The accepted manuscript of the publication may differ from the final published version.Background: The impact of air pollution on cognitive impairment in older people has not been fully understood. It is unclear which air pollutants are the culprit. Objective: We assessed the associations of six air pollutants and air quality index (AQI) with cognitive impairment. Methods: We examined 7,311 participants aged ≥60 years from the ZJMPHS cohort in China. They were interviewed for baseline socio-demographic and disease risk factors in 2014, and re-interviewed in 2015 and 2016, respectively. The presence of cognitive impairment was determined by the Chinese version of the Mini-Mental State Examination. Daily area-level data monitored for air pollution during 2013-2015 was then examined for associations with cognitive impairment in logistic regression models. Results: Over the two years follow-up, 1,652 participants developed cognitive impairment, of which 917 were severe cases. Continuous air pollution data showed the risk of cognitive impairment increased with exposure to PM2.5 (fully adjusted odds ratio [aOR] 1.04, 95% CI 1.01-1.08), PM10 (1.03, 1.001-1.06), and SO2 (1.04, 1.01-1.08), but not with NO2, CO, O3, and AQI. Categorized data analysis for low, middle, and high level exposure demonstrated that the aOR increased with PM2.5 and AQI, somehow with PM10 and CO, but not significantly with SO2 and NO2, and decreased with O3. The patterns for these associations with severe cognitive impairment were stronger. Conclusion: Lowering PM2.5, PM10, SO2, and CO level could reduce the risk of cognitive impairment in older Chinese. Strategies to target most important air pollutants should be an integral component of cognitive interventions.Zhejiang Provincial Public Welfare Technology Application Research Project of China (LGF19H260003) and an EU grant from Horizon 2020 MSCA – DEMAIRPO #799247.Published versio