Latest ArticlesVoltage-dependent anion channels (VDACs), which are located at the mitochondrial outer membrane, playing an important role in the regulation of mitochondrial energy metabolism and mitochondria- mediated apoptotic events, are considered as potential targets for tumor therapy. Studies have indicated that neurodegenerative diseases such as Alzheimer's disease (AD) generally lead to mitochondrial dysfunction. During this process, VDAC1, changing in expression, interacting with disease-related molecules, was involved in the occurrence and development of diseases. This review summarizes the characteristics and physiological functions of VDAC1, common important structural units and its role in apoptosis. The focus is on the research progress of VDAC1 in AD, as well as the effects in learning and memory related functions by modulating VDAC1 expression or function.
As a post-translational modification, protein acetylation plays an important role in the regulation of apoptosis, mitochondriopoiesis, lipid metabolism and cellular stress response. The imbalance of acetylation and deacetylation has been blamed for the tumorigenesis and malignant progression, which is gradually considered as a promising therapeutic target. Mammalian sirtuins, a NAD+ dependent class Ⅲ HDACs, are closely related to the development of aging, tumor, diabetes, obesity and neurodegenerative diseases. To provide a theoretical basis for the development of new anti-tumor drugs and the treatment of malignant tumors, this paper is prepared to focus on the irreplaceable role of sirtuins in tumor evolution:maintaining genomic stability, regulating energy metabolism, and facilitating tumor cells stemness. The modulator and pathways of sirtuins family and the research progress of agonists and inhibitors are also reviewed. The functions of SIRT2 in resistance, proliferation and metastasis have been highlighted.
IDO1 (indoleamine 2, 3-dioxygenase 1) is one of the most significant checkpoint in tumor immunology. Numerous studies indicates that IDO1 is abnormally expressed in breast cancer, colorectal cancer, liver cancer and other tumor tissues, participating in tumor immune escape through multiple pathways. This review is prepared to elucidate the biological function of IDO1, highlight its pivotal role in tumor evasion, and summarize IDO1 inhibitors in the clinical trials.
Phage display technology utilizes filamentous phage display proteins and polypeptides to extract a desired polypeptide or protein from a large number of variants. The antibody fragments screened and obtained by phage display library technology play an important role in disease diagnosis and treatment. This article briefly introduces the principles of phage display technology, summarizes the development of monoclonal antibodies, the development of antigenic microbial vaccines, and the application of peptide drugs. This review highlights the importance of phage display technology in the diagnosis and treatment of various human diseases such as cancer and autoimmune diseases etc.
Inflammatory bowel disease (IBD) is a chronic relapsing inflammatory disorder including mainly ulcerative colitis (UC) and Crohn's disease (CD). In China, IBD has become a common disease of the digestive system with an dramatic increase in incidence in recent years. The pathogenesis of IBD is not yet clear, and no drugs can completely cure IBD. Compared with monoclonal antibody drugs, small molecule drugs have the advantages of low cost, easy development as oral agents, and absence of immunogenicity. This review summarizes the recent research and development of small molecule immunosuppressants for IBD.
Three-dimensional (3D) printing technology is a rapid prototyping technology for designing 3D models with special shape and complex internal structure via computer-aided/controlled drawing and preparing. This technology displays the characteristics of flexible processing, rapid shaping, low operating cost and high reliability. 3D printing technology may provide new strategies and approaches for the generation of a variety of new drug delivery systems, which makes its application in pharmaceutics attractive. This review briefly introduces the process and feature of 3D printing technology in preparation field and mainly introduces the research progress in the design and engineering of related preparations in the aspects of rate-controlled drug release, time-controlled drug release and targeted drug release. The prospects and challenges of 3D printing technology in the formulation engineering are analyzed.
Supersaturated drug delivery systems (SDDS) are defined as systems that are able to generate and maintain a sustained drug supersaturation in the gastrointestinal tract, facilitating the oral absorption of drugs with poor water solubility. Supersaturated drug solution is generated from a higher energy form of the drug or rapid dissolution through various formulation options. However, supersaturated solution is a thermodynamically unstable system that can easily lead to drug precipitation, missing the aim of improving the absorption. Therefore, maintenance of the supersaturated state is essential for the development of SDDS. Polymer-based SDDS take polymers as the precipitation inhibitor, which can effectively prevent the precipitation of drugs, generating an excellent effect on maintenance of the stability of supersaturated solution. However, different polymers have distinct anti-precipitation ability, and the mechanisms of such activity supported by the polymer remain unrevealed. In this review, we summarize the research advances in the absorption-enhancing mechanisms and in vitro evaluations of polymers-based SDDS. This review provides a reference for the design of rational SDDS.
Oxcarbazepine (OXC) is a common antiepileptic drugs. In this study, one hundred and eighty four epilepsy patients with 196 observations of oxcarbazepine's active metabolite, 10, 11-dihydro-10-monohydroxy carbazepine (MHD) were collected prospectively from routine clinical monitoring. Nonlinear mixed effect modeling was employed to develop a population pharmacokinetic model of oxcarbazepine in Chinese patients with epilepsy to investigate the impact of gender, age, weight, co-medications and genetic polymorphisms of UGT2B7 c.802T > C, ABCC2 c.1249G > A, ABCC 23972C > T on pharmacokinetic characteristics of OXC. The population estimate of apparent clearance (CL/F) and apparent volume of distribution (V/F) was 1.84 L·h−1 and 275 L, respectively. Gender and UGT2B7 c.802T > C affected the clearance rate of MHD significantly. The established model was:CL/F=1.84×0.848UGT2B7×1.17GENDER. Where the genotype of UGT2B7 c.802T > C was CC, UGT2B7=0, otherwise UGT2B7=1. When the patient was male, GENDER=1, otherwise GENDER=0. The final model was evaluated by normalized predictive distribution error (NPDE) and bootstrap method. The model was stable and reliable, which offers a powerful approach for rational use of OXC in epilepsy patients.
In this study, the effects of honokiol (HN) treatment for 24 h on lipid synthesis was examined in HepG2 cells. The parameters include intracellular lipid droplet and the expression of SREBP-1c and PNPLA3, glucose uptake, and oxidative stress including the expression of CYP2E1 and CYP4A in normal, TO901317 (TO)- and oleic acid (OA)-treated HepG2 cells. The lipid droplets were detected by oil red O staining. The glucose uptake was measured by fluorescence spectrophotometry using[2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2-deoxyglucose, 2-NBDG] as probe. The expression levels of target genes were detected by quantitative PCR and Western blot. The results showed that:① TO (5 μmol·L-1) and OA (0.5 mmol·L-1) treatment increased the levels of intracellular lipid accumulation and the mRNA and protein expression of SREBP-1c and PNPLA3. After HN (10, 20, 40 μmol·L-1) treatment for 24 h, the lipid accumulation and the expression of SREBP-1c and PNPLA3 were all decreased in the tested cells. ② OA treatment significantly suppressed glucose uptake, while HN treatment dose-dependently increased the glucose uptake in OA-treated cells. ③ Compared with control group, CYP2E1 protein level significantly decreased in the three tested cells, and CYP4A protein level significantly decreased only in OA-treated cells following HN treatment. The above results suggest that HN may attenuate lipid accumulation by suppressing the expression of SREBP-1c and PNPLA3, and reduce lipid peroxidation and insulin resistance by down-regulation of the protein levels of CYP2E1 and CYP4A in HepG2 cells with steatosis.
Present study was designed to investigate the effects and underlying antioxidant mechanism of klotho overexpression through an intracerebroventricular injection of a lentiviral vector that encoded murine klotho (LV-KL) on cerebral ischemia injury. Four weeks after the injection of lentivirus into the lateral ventricle of C57Balc/6J mice, a mouse model of global cerebral ischemia-reperfusion was established by bilateral common carotid artery occlusion (2VO). Klotho overexpression significantly improved neurobehavioral deficits and increased the number of survival neurons in the hippocampal CA1 and caudate putamen subregions. The overexpression also decreased malondialdehyde (MDA) content in brain, while mitochondrial manganese- superoxide dismutase (Mn-SOD) and catalase (CAT) expression in brain were increased. Moreover, klotho overexpression decreased Akt and forkhead box class O1 phosphorylation. These findings suggest that klotho may compensate for its aging-related decline to provide a promising therapeutic approach for the acute ischemic stroke during aging.
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