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1.
Unleashing the Potential of Camptothecin: Exploring Innovative Strategies for Structural Modification and Therapeutic Advancements.
Chen, Z, Liu, M, Wang, N, Xiao, W, Shi, J
Journal of medicinal chemistry. 2024;(5):3244-3273
Abstract
Camptothecin (CPT) is a potent anti-cancer agent targeting topoisomerase I (TOP1). However, CPT has poor pharmacokinetic properties, causes toxicities, and leads to drug resistance, which limit its clinical use. In this paper, to review the current state of CPT research. We first briefly explain CPT's TOP1 inhibition mechanism and the key hurdles in CPT drug development. Then we examine strategies to overcome CPT's limitations through structural modifications and advanced delivery systems. Though modifications alone seem insufficient to fully enhance CPT's therapeutic potential, structure-activity relationship analysis provides insights to guide optimization of CPT analogs. In comparison, advanced delivery systems integrating controlled release, imaging capabilities, and combination therapies via stimulus-responsive linkers and targeting moieties show great promise for improving CPT's pharmacological profile. Looking forward, multifaceted approaches combining selective CPT derivatives with advanced delivery systems, informed by emerging biological insights, hold promise for fully unleashing CPT's anti-cancer potential.
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2.
OsmiR5519 regulates grain size and weight and down-regulates sucrose synthase gene RSUS2 in rice (Oryza sativa L.).
Guo, S, Li, Y, Wang, Y, Xu, Y, Li, Y, Wu, P, Wu, J, Wang, L, Liu, X, Chen, Z
Planta. 2024;(5):106
Abstract
The up-regulation of OsmiR5519 results in the decrease of grain size, weight and seed setting rate. OsmiR5519 plays important roles in the process of grain filling and down-regulates sucrose synthase gene RSUS2. MicroRNAs (miRNAs) are one class of small non-coding RNAs that act as crucial regulators of plant growth and development. In rice, the conserved miRNAs were revealed to regulate the yield components, but the function of rice-specific miRNAs has been rarely studied. The rice-specific OsmiR5519 was found to be abundantly expressed during reproductive development, but its biological roles remain unknown. In this study, the function of rice-specific OsmiR5519 was characterized with the miR5519-overexpressing line (miR5519-OE) and miR5519-silenced line (STTM5519). At seedling stage, the content of sucrose, glucose and fructose was obviously lower in the leaves of miR5519-OE lines than those of wild-type (WT) line. The grain size and weight were decreased significantly in miR5519-OE lines, compared to those of WT rice. The cell width of hull in miR5519-OE was smaller than that in WT. The seed setting rate was notably reduced in miR5519-OE lines, but not in STTM5519 lines. Cytological observation demonstrated that the inadequate grain filling was the main reason for the decline of seed setting rate in miR5519-OE lines. The percentage of the defects of grain amounted to 40% in miR5519-OE lines, which almost equaled to the decreased value of seed setting rate. Furthermore, the sucrose synthase gene RSUS2 was identified as a target of OsmiR5519 via RNA ligase-mediated 3'-amplification of cDNA ends (3'-RLM-RACE), dual luciferase assays and transient expression assays. In summary, our results suggest that OsmiR5519 regulates grain size and weight and down-regulates RSUS2 in rice.
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3.
BVES-AS1 suppresses the colorectal cancer progression via the miR-1269a/b-SVEP1-PI3K/AKT axis.
Yang, J, Deng, Q, Chen, Z, Chen, Y, Fu, Z
Advances in clinical and experimental medicine : official organ Wroclaw Medical University. 2024
Abstract
BACKGROUND Numerous studies have indicated the engagement of long non-coding RNA (lncRNA) in various cancer types, including colorectal cancer (CRC). However, the functional and mechanistic roles of lncRNAs in CRC remain largely elusive. OBJECTIVES The aim of this study was to explore the function and mechanism of lncRNA BVES-AS1 in CRC. MATERIAL AND METHODS The expression levels of BVES-AS1 were validated in CRC tissues and paired normal samples using quantitative real-time polymerase chain reaction (qPCR) Subsequently, the biological functions of BVES-AS1 in CRC cells were investigated both in vitro and in vivo. Various experimental techniques such as western blot, fluorescence in situ hybridization, RNA-sequencing (RNA-seq), biotin-labeled miRNA pulldown assay, dual-luciferase reporter gene assay, and RNA-protein immunoprecipitation (RIP) assay were employed to elucidate the potential mechanism of BVES-AS1. RESULTS The findings of this study demonstrated that BVES-AS1 expression was downregulated in CRC tissues compared to normal tissues, and its expression level was associated with tumor infiltration and tumor-nodule-metastasis (TNM) stage. Furthermore, BVES-AS1 was found to suppress CRC cell proliferation, migration and metastasis both in vitro and in vivo. Mechanistically, BVES-AS1 acted as a sponge for miR-1269a and miR-1269b, thereby regulating SVEP1. Additionally, the silencing of SVEP1 activated the PI3K/AKT pathway. CONCLUSIONS These results suggest that BVES-AS1 plays a crucial role in the progression of CRC through the miR-1269a/b-SVEP1-PI3K/AKT axis, providing new insights into the therapeutic strategies for CRC.
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4.
A review on traditional Chinese medicine natural products and acupuncture intervention for Alzheimer's disease based on the neuroinflammatory.
Chen, Z, Wang, X, Du, S, Liu, Q, Xu, Z, Guo, Y, Lin, X
Chinese medicine. 2024;(1):35
Abstract
Alzheimer's disease (AD) is a neurodegenerative disease with insidious onset and progressive development. It is clinically characterized by cognitive impairment, memory impairment and behavioral change. Chinese herbal medicine and acupuncture are important components of traditional Chinese medicine (TCM), and are commonly used in clinical treatment of AD. This paper systematically summarizes the research progress of traditional Chinese medicine natural products and acupuncture treatment of AD, which combined with existing clinical and preclinical evidence, based on a comprehensive review of neuroinflammation, and discusses the efficacy and potential mechanisms of traditional Chinese medicine natural products and acupuncture treatment of AD. Resveratrol, curcumin, kaempferol and other Chinese herbal medicine components can significantly inhibit the neuroinflammation of AD in vivo and in vitro, and are candidates for the treatment of AD. Acupuncture can alleviate the memory and cognitive impairment of AD by improving neuroinflammation, synaptic plasticity, nerve cell apoptosis and reducing the production and aggregation of amyloid β protein (Aβ) in the brain. It has the characteristics of early, safe, effective and benign bidirectional adjustment. The purpose of this paper is to provide a basis for improving the clinical strategies of TCM for the treatment of AD.
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5.
Tris-assisted one-step fabrication of functional carbon dots for specific folate receptor positive-expressed cancer cell imaging.
Tong, L, Wang, X, Zhang, X, Xu, C, Qiao, M, Chen, Z, Tang, B
Talanta. 2024;:125904
Abstract
Specific staining of cancer cells is momentous for cancer research. Nanoprobe with multivalent recognition is emerging as powerful tools for bioimaging, but the nonspecific cell uptake and complex functional modification procedures are still obstacles for specific detection and convenient synthesis. Carbon dots (CDs) with an intrinsic targeting ability, excellent optical properties and biocompatibility acquired from an efficient one-step fabrication procedure were urgently desired in specific cancer cells visualization. Herein, inspired by the interrelationships between interface and biomolecular mechanisms, we suggested that it was possible to construct CDs with the desired characteristics for folate receptor (FR) positive-expressed cancer cell imaging via rich hydroxyl groups Tris-assisted one-step hydrothermal treatment of folate acid (FA) and l-Arginine (L-Arg) precursors. The prepared small-sized F-CDs were equipped with abundant hydroxyl, pterin and negative charge surface, and possessed environmental friendliness, outstanding photostability and biocompatibility. Moreover, F-CDs had an intrinsic FR positive-expressed cancer cell targeting ability without any post-modification of the ligands. Rich hydroxyl groups play a vital role in endowing the optical properties and biological effects of F-CDs. F-CDs could be used as a promising candidate for FR-expressed cancer cell labeling and tracking. In addition, the caveolae-mediated endocytosis pathway of F-CDs was ascertained. More importantly, experimental results confirmed that the combination of physicochemical properties may provide an efficient strategy to overcome non-specific cell uptake interactions for cell labeling. Our strategy put forward a promising alternative to design fluorescent CDs for extensive chemical and biomedical applications.
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6.
Biological Roles of 5-Oxo-6,8,11,14-Eicosatetraenoic Acid and the OXE Receptor in Allergic Diseases: Collegium Internationale Allergologicum Update 2024.
Lin, L, Dai, F, Wei, J, Chen, Z
International archives of allergy and immunology. 2024;:1-10
Abstract
BACKGROUND 5-Oxo-6,8,11,14-eicosatetraenoic acid (5-Oxo-ETE) is a metabolite of arachidonic acid shown to promote biological activities in different cell types. SUMMARY 5-Oxo-ETE is synthesized from the 5-lipoxygenase product 5S-HETE (5S-hydroxy-6,8,11,14-eicosatetraenoic acid) in the presence of the nicotinamide adenine dinucleotide phosphate (NADP)+-dependent enzyme 5-hydroxyeicosanoid dehydrogenase (5-HEDH). Under some conditions that promote oxidation of NADPH to NADP+, such as the respiratory burst in phagocytic cells, eosinophils, and neutrophils, oxidative stress in monocytes and dendritic cells, and cell death, 5-Oxo-ETE synthesis can be dramatically increased. In addition, 5-Oxo-ETE can also be formed in the absence of 5-lipoxygenase in cells through transcellular biosynthesis by inflammatory cell-derived 5S-HETE. This compound performs its biological activities by the highly selective Gi/o-coupled OXE receptor, which is highly expressed on eosinophils, neutrophils, basophils, and monocytes. As such, 5-Oxo-ETE is a potent chemoattractant for these inflammatory cells, especially for eosinophils. KEY MESSAGES Although the pathophysiological role of 5-Oxo-ETE is not clearly understood, 5-Oxo-ETE may be a significant mediator in allergic diseases, such as allergic asthma, allergic rhinitis, and atopic dermatitis. And targeting the OXE receptor may be a novel therapy for this kind of inflammatory condition. Nowadays, selective OXE receptor antagonists are currently under investigation and could become potential therapeutic agents in allergy.
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7.
ACP-Mediated Phase Transformation for Collagen Mineralization: A New Understanding of the Mechanism.
Shan, S, Tang, Z, Sun, K, Jin, W, Pan, H, Tang, R, Yin, W, Xie, Z, Chen, Z, Shao, C
Advanced healthcare materials. 2024;(2):e2302418
Abstract
Despite significant efforts utilizing advanced technologies, the contentious debate surrounding the intricate mechanism underlying collagen fibril mineralization, particularly with regard to amorphous precursor infiltration and phase transformation, persists. This work proposes an amorphous calcium phosphate (ACP)-mediated pathway for collagen fibril mineralization and utilizing stochastic optical reconstruction microscopy technology, and has experimentally confirmed for the first time that the ACP nanoparticles can infiltrate inside collagen fibrils. Subsequently, the ACP-mediated phase transformation occurs within collagen fibrils to form HAP crystallites, and significantly enhances the mechanical properties of the mineralized collagen fibrils compared to those achieved by the calcium phosphate ion (CPI)-mediated mineralization and resembles the natural counterpart. Furthermore, demineralized dentin can be effectively remineralized through ACP-mediated mineralization, leading to complete restoration of its mechanical properties. This work provides a new paradigm of collagen mineralization via particle-mediated phase transformation, deepens the understanding of the mechanism behind the mineralization of collagen fibrils, and offers a new strategy for hard tissue repair.
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8.
Emerging Contaminants: An Emerging Risk Factor for Diabetes Mellitus.
Niu, H, Xu, M, Tu, P, Xu, Y, Li, X, Xing, M, Chen, Z, Wang, X, Lou, X, Wu, L, et al
Toxics. 2024;(1)
Abstract
Emerging contaminants have been increasingly recognized as critical determinants in global public health outcomes. However, the intricate relationship between these contaminants and glucose metabolism remains to be fully elucidated. The paucity of comprehensive clinical data, coupled with the need for in-depth mechanistic investigations, underscores the urgency to decipher the precise molecular and cellular pathways through which these contaminants potentially mediate the initiation and progression of diabetes mellitus. A profound understanding of the epidemiological impact of these emerging contaminants, as well as the elucidation of the underlying mechanistic pathways, is indispensable for the formulation of evidence-based policy and preventive interventions. This review systematically aggregates contemporary findings from epidemiological investigations and delves into the mechanistic correlates that tether exposure to emerging contaminants, including endocrine disruptors, perfluorinated compounds, microplastics, and antibiotics, to glycemic dysregulation. A nuanced exploration is undertaken focusing on potential dietary sources and the consequential role of the gut microbiome in their toxic effects. This review endeavors to provide a foundational reference for future investigations into the complex interplay between emerging contaminants and diabetes mellitus.
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9.
Research Progress of Small Plant Peptides on the Regulation of Plant Growth, Development, and Abiotic Stress.
Ren, G, Zhang, Y, Chen, Z, Xue, X, Fan, H
International journal of molecular sciences. 2024;(7)
Abstract
Small peptides in plants are typically characterized as being shorter than 120 amino acids, with their biologically active variants comprising fewer than 20 amino acids. These peptides are instrumental in regulating plant growth, development, and physiological processes, even at minimal concentrations. They play a critical role in long-distance signal transduction within plants and act as primary responders to a range of stress conditions, including salinity, alkalinity, drought, high temperatures, and cold. This review highlights the crucial roles of various small peptides in plant growth and development, plant resistance to abiotic stress, and their involvement in long-distance transport. Furthermore, it elaborates their roles in the regulation of plant hormone biosynthesis. Special emphasis is given to the functions and mechanisms of small peptides in plants responding to abiotic stress conditions, aiming to provide valuable insights for researchers working on the comprehensive study and practical application of small peptides.
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10.
Experimental research on compressive strength deterioration of coal seam floor sandstone under the action of acidic mine drainage.
Han, W, Chen, Z, Liu, H, Zheng, X, Wu, J, Yuan, Q
Scientific reports. 2024;(1):4593
Abstract
In sulphur-coal symbiotic coal seams, after the mining of sulphide iron ore, when the coal resources are mined, the mine water accumulated in the roadway mining area will have a certain impact on the stability of the surrounding rock of the coal seam roadway. Taking the floor sandstone of sulfur coal symbiotic coal seam as the research object, the roof fissure water with pH values of 7.48, 4.81 and 2.62 was used as the experimental solution. 10 experimental schemes were designed to measure the compressive strength of the samples under the action of AMD, and the hydrochemical analysis of AMD was conducted. The pore structures of the samples before and after the action of AMD were analyzed. Based on the hydrochemistry and pore structure, the deterioration mechanism of compressive strength of the coal seam floor sandstone under the action of AMD was explained. The results indicated that the compressive strength of the samples decreased with the increasing action time of AMD. The compressive strength decreased with the increment of the porosity. The concentration of H+ ion in AMD was relatively small. Na2O in albite dissolved and reacted with water, leading to an increase in the concentration of Na+ ion. Soluble substances such as MgCl2 and CaSO4 in the pore structure dissolved, leading to an increase in the concentration of Ca2+ and Mg2+ ions. The dissolution of soluble substances and the physical-chemical reactions between solutions and minerals were the essential causes of the continuous deterioration of the compressive strength of the coal seam floor sandstone. The results of this study can provide a theoretical basis for the deterioration of the mechanical properties of the peripheral rock in the roadway of the sulphur coal seam, and can also provide a certain engineering reference for the sulphur coal seam roadway.