Latest ArticlesThe mammalian cell nucleus is highly structured and organized into various membrane-less nuclear compartments called nuclear bodies. Nuclear bodies are highly dynamic structures, with a variety of substances gathered inside to promote the more efficient conduct of certain biological reactions. It dynamically produces responses under different biological processes and stress conditions such as tumorigenesis, apoptosis, antiviral defense, and plays an important role in regulating cell homeostasis. Tumor is a major public health problem, and finding new targets is the key to tumor therapy. How the nuclear bodies are involved in the development of tumor has not been reported. This review aims to provide a new understanding of how the nuclear bodies regulates tumor progression and provide a new effective strategy for tumor prevention and treatment.
Type 2 diabetes mellitus (T2DM) is a complex metabolic disorder characterized by chronic hyperglycemia, hyperlipidemia, and peripheral insulin resistance. Endoplasmic reticulum stress (ERS), a response to cellular stress, is activated across various tissues during the progression of T2DM, leading to disruptions in protein synthesis. Notably, epithelial and endocrine cells with hormone-secreting functions are particularly vulnerable to functional impairments induced by ERS. The gut-pancreas axis is essential for regulating metabolism and the progression of T2DM. Intestinal epithelial L cells, integral to the intestinal barrier, can secrete the glucagon-like peptide-1 (GLP-1). This hormone promotes insulin secretion from pancreatic β-cells and plays a critical role in glucose metabolism. Importantly, ERS plays a critical role in regulating glucolipid-induced dysfunction of gut-pancreas axis. For instance, ERS is involved in regulating the intestinal barrier and the secretion of GLP-1 as well as insulin. Therefore, ERS can be a potential target for T2DM treatment. In this paper, we review the regulatory roles of ERS in the gut-pancreas axis during the development of T2DM, and summarize the therapeutic drugs and strategies targeting ERS for T2DM treatment.
The blood-brain barrier limits the brain delivery of most drugs and affects the treatment of central nervous system disorders. The transnasal drug delivery allows the drug to bypass the blood-brain barrier and reach the brain directly through pathways such as the olfactory and trigeminal nerves, thus improving the therapeutic efficacy of the drug while reducing drug degradation and avoiding hepatic first pass effect. With the rise of nanotechnology, the combination of nanoformulations with transnasal routes of administration is expected to achieve better brain targeting and treatment of brain diseases. On the basis of summarizing the characteristics of the various nose-to-brain pathways, this review summarizes the researches on novel transnasal nanopreparations such as exosomes and liquid crystals in recent years as well as new strategies to improve the efficiency of brain entry including focused ultrasound-mediated techniques. We also review the recent studies on transnasal brain entry nanopreparations in the treatment of various brain disorders and current research dilemmas, looking forward to the prospect of their future clinical applications.
This review introduced the research progress of covalent modification strategies in local anesthetic drug delivery systems. As a commonly used and multimodal analgesic drug, local anesthetics have limited duration of action and potential toxicity in clinical application. In order to prolong the analgesic effect and reduce systemic toxicity, researchers are committed to the development of sustained-release local anesthetics with long-lasting dose-controlled-release functions. When it comes to the delivery of local anesthetics, the covalent modification strategy is a key approach. By covalently binding drugs to large molecule carriers, covalent modification strategies can improve drug stability, targeting and delivery efficiency. Macromolecular prodrugs can modulate the kinetic process of the drug, so that the drug is released in the form of the active ingredient and achieve better therapeutic effects. In recent years, stimulus-responsive macromolecular prodrugs have become a research hotpot for local anesthetic drug delivery systems, and the stimulus-responsive performance of macromolecular prodrugs can rapidly release drugs under internal and external stimulus conditions, and maintain low toxicity and high efficiency in blood circulation and normal tissues. These emerging research directions provide important guidance for prolonging the analgesic effect of local anesthetics and reducing systemic toxicity, and provide new idea for the development of more effective drug delivery systems in the future.
The blood-brain barrier (BBB) plays a crucial role in maintaining the homeostasis of the brain's internal environment, which poses challenges to the treatment of central nervous system diseases. Drug carriers can aid in the delivery of therapeutic agents across the BBB to exert their pharmacological effects. The article reviewed the pathways for drug delivery across the BBB, the intracerebral fate and the classification of drug carriers and focuses on the functions and characteristics of liposomes, exosomes, apoptotic bodies, cell-penetrating peptides, and cell-targeting peptides. The review will provide an outlook on the future and challenge of research in the field of drug delivery across the BBB.
Administration oral mucosal drug delivery has the advantages of high patient acceptance, rapid onset of action, convenient, etc., and it can avoid the first-pass effect of the drug in the liver. Nevertheless, the design of oral mucosal drug delivery systems is inherently challenging due to the distinctive physicochemical properties of certain drugs and the specific physiological environment of the oral cavity. Natural polysaccharide chitosan-based materials exhibit favorable characteristics, including non-toxicity or low toxicity and biodegradability. These materials can effectively inhibit bacterial growth, enable controlled drug release, and enhance mucosal adhesion. Consequently, chitosan-based materials have been the subject of extensive research in the field of oral mucosal drug delivery systems. This paper offers a comprehensive overview of oral mucosal drug delivery systems, reviews relevant studies on chitosan-based materials, and discusses future prospects for their application.
The microsphere drug delivery systems have been extensively exploited for providing controllable drug release kinetics, enhancing drug stability and localized drug delivery. In past decade, dozens of microsphere drug delivery systems have been developed for clinical therapy of cancer, schizophrenia and neurodegenerative diseases (e.g., Alzheimer's disease and Parkinsonism). In this review article, we comprehensively summarized the fabrication methods of drug delivery systems and highlighted their advances for clinical application. Furthermore, we analyzed the potential and the challenges for clinical translation of the drug delivery systems.
Liver size is regulated by circadian clock and exhibits a diurnal rhythm. Pregnane X receptor (PXR) and peroxisome proliferator-activated receptor α (PPARα), members of nuclear receptor superfamily, are important regulators of liver size. We previously demonstrated that mPXR agonist pregnenolone 16α-carbonitrile (PCN) and mPPARα agonist pirinixic acid (WY-14643) promoted liver enlargement and liver regeneration after partial hepatectomy. However, whether PXR or PPARα activation-induced liver enlargement exhibits diurnal rhythm with normal liver diurnal oscillations remains unclear. The aim of this study was to investigate the diurnal rhythm of PXR or PPARα activation-induced liver enlargement. Male C57BL/6 mice were intraperitoneally injected with corn oil, PCN or WY-14643 for three days, and liver samples were weighed and collected at various time points for analysis. The animal experiment protocol was reviewed and approved by Institutional Animal Care and Use Committee of Sun Yat-sen University (approval No. SYSU-IACUC-2023-001613, SYSU-IACUC-2023-001783). The results showed that PXR or PPARα activation at various time points significantly induced liver enlargement, and liver size maintained normal diurnal oscillations during PXR or PPARα activation-induced hepatomegaly, without significant effects on the expression of core clock genes. This study reveals PXR or PPARα activation-induced liver enlargement exhibits diurnal rhythm with normal liver diurnal oscillations, and provides novel data for nuclear receptor-induced liver enlargement and liver diurnal rhythm.
Based on the octahedral modifiable structures and kinetic inertness, platinum (Ⅳ) complexes have become antitumor prodrug candidates to mitigate platinum (Ⅱ) drug resistance and side effects. The nitrobenzoxadiazole derivative (NBDHEX) can inhibit the activity of glutathione S-transferases (GSTs) and be introduced to conjugate with platinum(Ⅱ) complexes DN603 and DN604 to yield two platinum (Ⅳ) complexes DN603/DN604-NBD. In vitro assays demonstrated that DN603/DN604-NBD could significantly inhibit the proliferation of cisplatin-sensitive A549 and resistant A549/cDDP cancer cells. The uptake of DN603/DN604-NBD in A549/cDDP cells was much higher than that of cisplatin, causing a higher rate of cell apoptosis and a greater ratio of Bax/Bcl-2, the activation of caspase-3 and cleavage of DNA repair enzyme (PARP), inducing the mitochondria-dependent cell apoptosis pathway. DN603/DN604-NBD could induce higher reactive oxygen species (ROS) levels, significantly enhance phosphorylation of histone H2AX on Ser-139 (γ-H2AX) fluorescence intensity and cause a greater degree of DNA double-stranded damage. Studies have shown that GSTs kinase GSTP1 was highly expressed in cisplatin-resistant cancer cells. Moreover, DN603/DN604-NBD targeted GSTP1 to suppress its expression level. By using the ROS scavenger NAC and the c-Jun N-terminal kinase (JNK) inhibitor SP600125 in advance, it was found that DN603/DN604-NBD could significantly increase the number of living cells and decrease the phosphorylation levels of JNK and c-Jun. The results indicated that DN603/DN604-NBD could produce higher levels of ROS to activate JNK-mediated signaling pathway, induce apoptosis in tumor cells to overcome cisplatin resistance. All the animal experiments were approved by Animal Ethics Committee of Southeast University (grant No. 20210303025). In vivo assays confirmed that DN603/DN604-NBD could inhibit the growth of A549 xenograft tumors with nearly no toxicity and fewer side effects. Taken together, DN603/DN604-NBD are investigated as two potential novel platinum (Ⅳ) prodrug candidates for anticancer therapy.
Transmembrane serine protease 2 (TMPRSS2) is a cell surface protease widely present in the human body. It is involved in the infection of various viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and in the cell invasion, tumor growth and metastasis processes of prostate cancer. This study used Boc-Gln-Ala-Arg-AMC as the fluorescent substrate to determine the cleavage activity of TMPRSS2 towards SARS-CoV-2 S protein. Then cell-based screening model for TMPRSS2 inhibitors was established in Vero E6 cells overexpressing TMPRSS2 (Vero E6/TMPRSS2). Seven compounds exhibiting TMPRSS2 inhibitory activities with low toxicity were obtained through high-throughput screening (HTS) from natural and synthetic compound pure product library of National Center for Screening Novel Microbial Drugs. Surface plasmon resonance (SPR) has shown that the obtained inhibitors could bind to TMPRSS2 with moderate affinity in a dose dependent manner. Cell-cell fusion experiments have shown that the obtained inhibitors can inhibit the occurrence of S protein mediated cell-cell fusion by inhibiting TMPRSS2 cleavage of SARS-CoV-2 S protein in a concentration dependent manner. Preliminary pseudovirus experiment showed that the inhibitors may reduce the pseudovirus infection into Opti-HEK-293T-ACE2 cells to varying degrees. In a word, this study successfully established a cell-based HTS model for TMPRSS2 inhibitor and preliminarily confirmed that the seven screened inhibitors possessed in vitro anti-TMPRSS2 activities, providing new structural scaffolds for the development of new drugs against SARS-CoV-2.
No. 86 Xueyuan South Road, Haidian District, Beijing
010-62662699(Operation and Technical Support)
qkjq@cast.org.cn
Copyright © 2025 China Association for Science and Technology. All rights reserved. For all open access content, the relevant licensing terms apply.
Sponsored by the Office of the Leading Group for Cybersecurity and Informatization of CAST, and supported by Science and Technology Review Publishing House
