1.Metabolic basis of solute carrier transporters in treatment of type 2 diabetes mellitus.
Jiamei LE ; Yilong CHEN ; Wei YANG ; Ligong CHEN ; Jianping YE
Acta Pharmaceutica Sinica B 2024;14(2):437-454
Solute carriers (SLCs) constitute the largest superfamily of membrane transporter proteins. These transporters, present in various SLC families, play a vital role in energy metabolism by facilitating the transport of diverse substances, including glucose, fatty acids, amino acids, nucleotides, and ions. They actively participate in the regulation of glucose metabolism at various steps, such as glucose uptake (e.g., SLC2A4/GLUT4), glucose reabsorption (e.g., SLC5A2/SGLT2), thermogenesis (e.g., SLC25A7/UCP-1), and ATP production (e.g., SLC25A4/ANT1 and SLC25A5/ANT2). The activities of these transporters contribute to the pathogenesis of type 2 diabetes mellitus (T2DM). Notably, SLC5A2 has emerged as a valid drug target for T2DM due to its role in renal glucose reabsorption, leading to groundbreaking advancements in diabetes drug discovery. Alongside SLC5A2, multiple families of SLC transporters involved in the regulation of glucose homeostasis hold potential applications for T2DM therapy. SLCs also impact drug metabolism of diabetic medicines through gene polymorphisms, such as rosiglitazone (SLCO1B1/OATP1B1) and metformin (SLC22A1-3/OCT1-3 and SLC47A1, 2/MATE1, 2). By consolidating insights into the biological activities and clinical relevance of SLC transporters in T2DM, this review offers a comprehensive update on their roles in controlling glucose metabolism as potential drug targets.
2.Percutaneous ablation of liver metastases from colorectal cancer: a comparison between the outcomes of ultrasound guidance and CT guidance using propensity score matching
Ma LUO ; Sheng PENG ; Guang YANG ; Letao LIN ; Ligong LU ; Jiawen CHEN ; Fujun ZHANG ; Fei GAO
Ultrasonography 2023;42(1):54-64
Purpose:
The aim of this study was to compare the effectiveness and outcomes of percutaneous ablation guided by ultrasonography (US) and computed tomography (CT) in colorectal liver oligometastases (CLOM).
Methods:
This study included patients with CLOM treated with percutaneous ablation from January 2008 to January 2021 in this observational study. Only lesions visualized on both CT and US images were further analyzed according to whether patients’ initial ablation treatments utilized US guidance or CT guidance. The Kaplan-Meier method was used to estimate local tumor progression (LTP)–free survival after propensity score matching (PSM). The LTP-free survival and treatment-related outcomes were compared between these two groups.
Results:
PSM identified 116 patients from each group, with 269 and 238 lesions in the USguided and CT-guided groups, respectively. US-guided ablation had a shorter average procedure time and lower cost than CT-guided ablation (27.54±12.06 minutes vs. 32.70±13.88 minutes, P=0.003; $2,175.13±618.17 vs. $2,455.49±710.25, P=0.002). For patients >60 years of age, the cumulative LTP rate at 1 year was lower in the US-guided group than in the CT-guided group (17.8% vs. 25.1%, P=0.038). For patients with perivascular liver lesions, the cumulative LTP rate at 1 year was lower in the US-guided group (14.4% vs. 28.2%, P=0.040).
Conclusion
For patients whose age is >60 years or who have perivascular liver lesions, USguided ablation is better than CT-guided ablation, with a shorter treatment time and lower costs when both ablation methods are feasible for patients.
3.Advance in the degradation of biodegradable plastics in different environments.
Yan JIN ; Fanfan CAI ; Ligong WANG ; Chao SONG ; Wenxiong JIN ; Junfang SUN ; Guangqing LIU ; Chang CHEN
Chinese Journal of Biotechnology 2022;38(5):1784-1808
With the continuously increasing demands of plastic products in the current society, the challenge of disposing plastic waste is constantly increasing, leading to the urgent need of mitigating plastic pollution. As a consequence, much attention has been paid to biodegradable plastics due to their degradability in a bio-active environment under certain conditions. Biodegradable plastics herald vast development potentials and considerable market prospects. The degradation of numerous types of biodegradable plastics will be affected by many factors. A thorough understanding of degradation mechanisms as well as functional microbial strains and enzymes is the key to comprehensive utilization and efficient treatment and disposal of biodegradable plastics. The article summarized the types, properties, advantages and disadvantages, and main applications of common biodegradable plastics. The degradation mechanisms, functional microbial strains and enzymes, as well as the degradation degree and duration under different environmental conditions, were also summarized. This review may help better understand the degradation of biodegradable plastics wastes.
Biodegradable Plastics
;
Biodegradation, Environmental
4.Memory T cells: strategies for optimizing tumor immunotherapy.
Qingjun LIU ; Zhongjie SUN ; Ligong CHEN
Protein & Cell 2020;11(8):549-564
Several studies have demonstrated that memory T cells including stem cell memory (Tscm) T cells and central memory (Tcm) T cells show superior persistence and antitumor immunity compared with effector memory T (Tem) cells and effector T (Teff) cells. Furthermore, the Tcm/Teff ratio has been reported to be a predictive biomarker of immune responses against some tumors. Thus, a system-level understanding of the mechanisms underlying the differentiation of effector and memory T cells is of increasing importance for developing immunological strategies against various tumors. This review focuses on recent advances in efficacy against tumors, the origin, formation mechanisms of memory T cells, and the role of the gut microbiota in memory T cell formation. Furthermore, we summarize strategies to generate memory T cells in (ex) vivo that, might be applicable in clinical practice.
5.Solute carrier transporters: the metabolic gatekeepers of immune cells.
Wenxin SONG ; Danyuan LI ; Lei TAO ; Qi LUO ; Ligong CHEN
Acta Pharmaceutica Sinica B 2020;10(1):61-78
Solute carrier (SLC) transporters meditate many essential physiological functions, including nutrient uptake, ion influx/efflux, and waste disposal. In its protective role against tumors and infections, the mammalian immune system coordinates complex signals to support the proliferation, differentiation, and effector function of individual cell subsets. Recent research in this area has yielded surprising findings on the roles of solute carrier transporters, which were discovered to regulate lymphocyte signaling and control their differentiation, function, and fate by modulating diverse metabolic pathways and balanced levels of different metabolites. In this review, we present current information mainly on glucose transporters, amino-acid transporters, and metal ion transporters, which are critically important for mediating immune cell homeostasis in many different pathological conditions.
6.Quantitative assessment of blood-brain barrier permeability and its application in patients with acute ischemic stroke
Ligong HUO ; Yu WANG ; Beilei CHEN ; Hailong YU ; Jun LI
International Journal of Cerebrovascular Diseases 2019;27(4):287-293
The occurrence,development and reperfusion treatment of ischemic stroke may damage the structure and function of the blood-brain barrier,leading to increased permeability of the blood-brain barrier,and then having cerebral edema or hemorrhagic transformation,and finally resulting in poor outcome.Quantitative assessment of blood-brain barrier permeability is now available.This article reviews the assessment methods of blood-brain barrier permeability and their application in patients with ischemic stroke.
7.The zinc transporter Slc39a5 controls glucose sensing and insulin secretion in pancreatic β-cells via Sirt1- and Pgc-1α-mediated regulation of Glut2.
Xinhui WANG ; Hong GAO ; Wenhui WU ; Enjun XIE ; Yingying YU ; Xuyan HE ; Jin LI ; Wanru ZHENG ; Xudong WANG ; Xizhi CAO ; Zhuoxian MENG ; Ligong CHEN ; Junxia MIN ; Fudi WANG
Protein & Cell 2019;10(6):436-449
Zinc levels are high in pancreatic β-cells, and zinc is involved in the synthesis, processing and secretion of insulin in these cells. However, precisely how cellular zinc homeostasis is regulated in pancreatic β-cells is poorly understood. By screening the expression of 14 Slc39a metal importer family member genes, we found that the zinc transporter Slc39a5 is significantly down-regulated in pancreatic β-cells in diabetic db/db mice, obese ob/ob mice and high-fat diet-fed mice. Moreover, β-cell-specific Slc39a5 knockout mice have impaired insulin secretion. In addition, Slc39a5-deficient pancreatic islets have reduced glucose tolerance accompanied by reduced expression of Pgc-1α and its downstream target gene Glut2. The down-regulation of Glut2 in Slc39a5-deficient islets was rescued using agonists of Sirt1, Pgc-1α and Ppar-γ. At the mechanistic level, we found that Slc39a5-mediated zinc influx induces Glut2 expression via Sirt1-mediated Pgc-1α activation. These findings suggest that Slc39a5 may serve as a possible therapeutic target for diabetes-related conditions.
8.DeepCPI:A Deep Learning-based Framework for Large-scale in silico Drug Screening
Wan FANGPING ; Zhu YUE ; Hu HAILIN ; Dai ANTAO ; Cai XIAOQING ; Chen LIGONG ; Gong HAIPENG ; Xia TIAN ; Yang DEHUA ; Wang MING-WEI ; Zeng JIANYANG
Genomics, Proteomics & Bioinformatics 2019;17(5):478-495
Accurate identification of compound-protein interactions (CPIs) in silico may deepen our understanding of the underlying mechanisms of drug action and thus remarkably facilitate drug discovery and development. Conventional similarity-or docking-based computational methods for predicting CPIs rarely exploit latent features from currently available large-scale unlabeled com-pound and protein data and often limit their usage to relatively small-scale datasets. In the present study, we propose DeepCPI, a novel general and scalable computational framework that combines effective feature embedding (a technique of representation learning) with powerful deep learning methods to accurately predict CPIs at a large scale. DeepCPI automatically learns the implicit yet expressive low-dimensional features of compounds and proteins from a massive amount of unla-beled data. Evaluations of the measured CPIs in large-scale databases, such as ChEMBL and Bind-ingDB, as well as of the known drug-target interactions from DrugBank, demonstrated the superior predictive performance of DeepCPI. Furthermore, several interactions among small-molecule compounds and three G protein-coupled receptor targets (glucagon-like peptide-1 recep-tor, glucagon receptor, and vasoactive intestinal peptide receptor) predicted using DeepCPI were experimentally validated. The present study suggests that DeepCPI is a useful and powerful tool for drug discovery and repositioning. The source code of DeepCPI can be downloaded from https://github.com/FangpingWan/DeepCPI.
9.Effect of contrast media on renal function in patients with cerebrovascular disease complicated by diabetes mellitus after receiving interventional treatment
Zaigang LÜ ; Linna WANG ; Xiaohui CHEN ; Ligong ZHANG ; Mengfei ZHONG ; Haiting LI ; Zhijie YANG ; Min LI ; Tianping TANG ; Zongen GAO
Journal of Interventional Radiology 2018;27(3):277-280
Objective To evaluate the effect of contrast medium on the renal function in patients with cerebrovascular disease accompanied by diabetes mellitus after receiving neuro - interventional therapy. Methods The clinical data of a total of 108 patients with cerebrovascular disease complicated by diabetes mellitus type 2, who were treated with neuro - interventional therapy during the period from March 2013 to March 2016, were retrospectively analyzed. The contrast dose used in interventional procedures was less than 250ml in each patient. The preoperative and 24 h -postoperative serum creatinine (sCr), serum cystatin C (Cys C) levels were determined, and based on the modification of dietary renal disease (MDRD) equation and Larsson equation the estimated glomerular filtration rates (eGFR) were separately calculated. Results Compared with preoperative values, the 24 h - postoperative mean sCr and Cys C levels were increased significantly (P=0. 001, P=0. 015 respectively), while the average eGFR rates were remarkably decreased (P< 0. 000 1 by using MDRD equation, and P=0. 021 by using Larsson equation). No kidney damage that needed to be treated occurred in all patients. Conclusion The contrast dose used in neuro - interventional procedures can cause decline of renal function in patients with type 2 diabetes mellitus. The combined determination of sCr and Cys C levels is helpful for the detection of contrast - induced changes in renal function as early as possible. The use of conventional dose of contrast agent in neuro - interventional procedures is safe for patients with type 2 diabetes mellitus. (J Intervent Radiol, 2018, 27:277-280)
10.Changes of cerebral white matter in patients with medication-overuse headache
Ligong ZHANG ; Chunfu CHEN ; Na ZHANG ; Yuan CHEN ; Congcong LI ; Xiaojun DIAO
Chinese Journal of Nervous and Mental Diseases 2017;43(7):415-419
Objective To investigate the microstructural abnormalities of cerebral white matter in patients with medication-overuse headache with diffusion tensor imaging.Methods Diffusion tensor magnetic resonance imaging (DT-MRI) was carried out in 80 migraine patients with medication-overuse headache (case group) and 80 age-and sex-matched healthy controls (control group).Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) were measured and the correlation between clinical characteristics and the changes was examined.Results ① The FA values at the bilateral orbitofrontal cortex,cingulate cortex,splenium of the corpus callosum and the right anterior limb of the capsula interna were significantly lower than those in the controls(P<0.05).② The ADC values at the right orbitofrontal cortex,left inferior frontal gyrus and anterior cingulate cortex were significantly higher than those in the controls (P<0.05).③ There were negative correlations between FA values at the bilateral orbitofrontal cortex and right hind legs of the capsula interna and headache course as well as frequency.There was negative correlation between FA values at the left hind legs of capsula interna and headache frequency.④ There were positive correlations between ADC values at the left orbitofrontal cortex and headache course as well as frequency.There were positive correlations between ADC values at the right orbitofrontal cortex and prior cingulate cortex and headache frequency.There was positive correlation between ADC values at the posterior cingulate cortex and headache course.Conclutions There might be an integrity change of neurofibrotic microstructures in the bilateral orbitofrontal cortex and cingulate cortex in patients with medication-overuse headache,FA values are negatively associated with headache course and frequency whereas ADC values are positively associated with headache course and frequency.

Result Analysis
Print
Save
E-mail