Tao Jiang

The occurrence of obesity has increased across the whole world. Many epidemiological studies have indicated that obesity strongly contributes to the development of cancer, cardiovascular diseases, type 2 diabetes, liver diseases and other disorders, accounting for a heavy burden on the public and on health-care systems every year. Excess energy uptake induces adipocyte hypertrophy, hyperplasia and formation of visceral fat in other non-adipose tissues to evoke cardiovascular disease, liver diseases. Adipose tissue can also secrete adipokines and inflammatory cytokines to affect the local microenvironment, induce insulin resistance, hyperglycemia, and activate associated inflammatory signaling pathways. This further exacerbates the development and progression of obesity-associated diseases. Although some progress in the treatment of obesity has been achieved in preclinical and clinical studies, the progression and pathogenesis of obesity-induced diseases are complex and unclear. We still need to understand their links to better guide the treatment of obesity and associated diseases. In this review, we review the links between obesity and other diseases, with a view to improve the future management and treatment of obesity and its co-morbidities.

The National Genomics Data Center (NGDC), which is a part of the China National Center for Bioinformation (CNCB), offers a comprehensive suite of database resources to support the global scientific community. Amidst the unprecedented accumulation of multi-omics data, CNCB-NGDC is committed to continually evolving and updating its core database resources through big data archiving, integrative analysis and value-added curation. Over the past year, CNCB-NGDC has expanded its collaborations with international databases and established new subcenters focusing on biodiversity, traditional Chinese medicine and tumor genetics. Substantial efforts have been made toward encompassing a broad spectrum of multi-omics data, developing innovative resources and enhancing existing resources. Notably, new resources have been developed for single-cell omics (scTWAS Atlas), genome and variation (VDGE), health and disease (CVD Atlas, CPMKG, Immunosenescence Inventory, HemAtlas, Cyclicpepedia, IDeAS), biodiversity and biosynthesis (RefMetaPlant, MASH-Ocean) and research tools (CCLHunter). All resources and services are publicly accessible at https://ngdc.cncb.ac.cn.

Camptothecin (CPT) was discovered from plant extracts more than 60 years ago. Since then, only two CPT analogues (irinotecan and topotecan) have been approved for cancer treatment, although several thousand CPT derivatives have been synthesized and many of them were actively studied in our research community over the past 6+ decades. In this review article, we briefly summarize: (1) the discovery and early development of CPTs, (2) the recognized CPT mechanism of action (MOA), (3) the synthesis of CPT and CPT analogues, and (4) the structure-activity relationship (SAR) of CPT and its analogues. Next, we provide evidence that certain CPT analogues can exert improved efficacy with low toxicity independently of topoisomerase I (Top1) inhibition; instead, these CPT analogues use novel MOAs by targeting important cancer survival-associated oncogenic proteins and/or by bypassing various treatment-resistant mechanisms. We then present a comprehensive review of the most advanced CPT analogues in clinical development, with the goal of resolving why no new CPTs have been FDA approved for cancer treatment, beyond irinotecan and topotecan. We argue that new CPT Top1 inhibitor drugs are unlikely being found to be significantly better than irinotecan and/or topotecan in terms of the overall antitumor activity and toxicity. The significance of CPT analogues that possess novel MOAs has not been sufficiently recognized so far. In our opinion, this is a research area with great potential to make a breakthrough for development of the next generation of CPT analogues that possess high efficacy (due to novel targets) and low toxicity (due to low inhibition of Top1 activity/function) for effective treatment of human disease, including cancer.

We report the discovery of a promising NDM-1 inhibitor, ebselen, through a cell-based screening approach. Enzymatic kinetic study and ESI-MS analysis suggested that ebselen could bind to NDM-1 by forming a S-Se bond with the Cys(221) residue at the active site, thereby exhibiting a new inhibition mechanism with broad spectrum inhibitory potential.