다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

[신간의 별자리x] 우리/미술, 그리고 ‘슬픔의 박물관’

https://bioone.org/journals/harvard-papers-in-botany/volume-13/issue-2/1043-4534-13.2.299/Flora-of-China/10.3100/1043-4534-13.2.299.pdf

Flora of China

Since the publication of the human reference genome, the identities of specific genes associated with human diseases are being discovered at a rapid rate. A central problem is that the biological activity of these genes is often unclear. Detailed investigations in model vertebrate organisms, typically mice, have been essential for understanding the activities of many orthologues of these disease-associated genes. Although gene-targeting approaches and phenotype analysis have led to a detailed understanding of nearly 6,000 protein-coding genes, this number falls considerably short of the more than 22,000 mouse protein-coding genes. Similarly, in zebrafish genetics, one-by-one gene studies using positional cloning, insertional mutagenesis, antisense morpholino oligonucleotides, targeted re-sequencing, and zinc finger and TAL endonucleases have made substantial contributions to our understanding of the biological activity of vertebrate genes, but again the number of genes studied falls well short of the more than 26,000 zebrafish protein-coding genes. Importantly, for both mice and zebrafish, none of these strategies are particularly suited to the rapid generation of knockouts in thousands of genes and the assessment of their biological activity. Here we describe an active project that aims to identify and phenotype the disruptive mutations in every zebrafish protein-coding gene, using a well-annotated zebrafish reference genome sequence, high-throughput sequencing and efficient chemical mutagenesis. So far we have identified potentially disruptive mutations in more than 38% of all known zebrafish protein-coding genes. We have developed a multi-allelic phenotyping scheme to efficiently assess the effects of each allele during embryogenesis and have analysed the phenotypic consequences of over 1,000 alleles. All mutant alleles and data are available to the community and our phenotyping scheme is adaptable to phenotypic analysis beyond embryogenesis.

A Systematic Genome-Wide Analysis of Zebrafish Protein-Coding Gene Function

Second near-infrared photothermal therapy (NIR-II PTT, 1000-1500 nm) has recently emerged as a new phototherapeutic modality with the advantages of deeper penetration, less energy dissipation and minimal normal-tissue toxicity over traditional first NIR PTT (750-1000 nm). However, suboptimal photothermal conversion and limited therapeutic efficacy remain the major challenges for NIR-II PTT. With the convergence in materials science, nanomedicine and biology, multifunctional NIR-II photothermal inorganic or organic materials have been extensively developed to combine NIR-II PTT with other therapeutic modalities for improved efficacies in treating life-threatening diseases including cancer and infection. This review summarizes the recent advances of NIR-II photothermal combinational theranostics pertinent to chemotherapy, immunotherapy, radiotherapy, and photodynamic, sonodynamic, chemodynamic, gene, gas, ionic, vascular and magnetothermal therapy. Potential obstacles and perspectives for future research and clinical translation of this new theranostic modality are also discussed.

Second near-infrared photothermal materials for combinational nanotheranostics

Due to the complexity of multifactorial diseases, single-target drugs do not always exhibit satisfactory efficacy. Recently, increasing evidence indicates that simultaneous modulation of multiple targets may improve both therapeutic safety and efficacy, compared with single-target drugs. However, few multitarget drugs are on market or in clinical trials, despite the best efforts of medicinal chemists. This article discusses the systematic establishment of target combination, lead generation, and optimization of multitarget-directed ligands (MTDLs). Moreover, we analyze some MTDLs research cases for several complex diseases in recent years and the physicochemical properties of 117 clinical multitarget drugs, with the aim to reveal the trends and insights of the potential use of MTDLs.

Rational Design of Multitarget-Directed Ligands: Strategies and Emerging Paradigms

Medicinal uses, phytochemistry and pharmacology of the genus Uncaria.

Donepezil-based multi-functional cholinesterase inhibitors for treatment of Alzheimer's disease.

Designing multitarget-directed ligands (MTDLs) is considered to be a promising approach to address complex and multifactorial maladies such as Alzheimer’s disease (AD) The concurrent inhibition of the two crucial AD targets, glycogen synthase kinase-3β (GSK-3β) and human acetylcholinesterase (hAChE), might represent a breakthrough in the quest for clinical efficacy Thus, a novel family of GSK-3β/AChE dual-target inhibitors was designed and synthesized Among these hybrids, 2f showed the most promising profile as a nanomolar inhibitor on both hAChE (IC50 = 65 nM) and hGSK-3β kinase activity (IC50 = 66 nM) It also showed good inhibitory effect on β-amyloid self-aggregation (inhibitory rate = 46%) at 20 μM Western blot analysis revealed that compound 2f inhibited hyperphosphorylation of tau protein in mouse neuroblastoma N2a-Tau cells In vivo studies confirmed that 2f significantly ameliorated the cognitive disorders in scopolamine-treated ICR mice and less hepatotoxicity than tacrine This study provi

Dual GSK-3β/AChE Inhibitors as a New Strategy for Multitargeting Anti-Alzheimer's Disease Drug Discovery.

Photodynamic therapy relies on photosensitizers to generate cytotoxic reactive oxygen species (ROS) resulting in the apoptois of tumor cells. However, there is an antioxidant system that impedes the elevation of oxidation levels in tumor cells. Thus, photodynamic therapy may exhibit insufficient curative effects due to ungenerous reactive oxygen species levels. Herein, we describe tumor-specific activated photodynamic therapy using an oxidation-regulating strategy. Methods: We first synthesised a reactive oxygen species-sensitive amphipathic prodrug of gambogic acid-grafted hyaluronic acid (HA-GA). The hydrophobic photosensitizer chlorin e6 (Ce6) was then loaded into HA-GA by hydrophobic interactions between GA and Ce6, forming amphipathic nanomicelles (HA-GA@Ce6). The ROS-responsive behavior, cytotoxicity, cell uptake, tumor cell killing, in vivo biodistribution and in vivo anti-tumor efficacy of HA-GA@Ce6 were investigated. The in vitro and in vivo experiments were performed on 4T1 murine breast cancer cells and 4T1 tumor model. Results: We validated that the micelles of HA-GA@Ce6 showed stronger cell uptake in 4T1 tumor cells and lower cytotoxicity in normal cells compared with free Ce6 and GA, which exhibited the benefits of nanomicelles on enhancing the tumor cell acumulation and reducing the side effects on normal cells synchronously. Additionally, the cytotoxic free radicals of photodynamic therapy were generated after irradiation and the high oxidation levels activated the ROS-sensitive GA prodrug efficiently, which killed the tumor cells and depleted intracellular glutathione (GSH), thereby impairing antioxidant levels and enhancing photodynamic therapy. Conclusion: With the successfully eradicated tumor growth in vivo. Our work represents a new photodynamic therapy concept, achieving superior anti-tumor efficacy by reducing intracellular antioxidant levels.

Wei Qu

Papers

Rational Design of Multitarget-Directed Ligands: Strategies and Emerging Paradigms

Medicinal uses, phytochemistry and pharmacology of the genus Uncaria.

Donepezil-based multi-functional cholinesterase inhibitors for treatment of Alzheimer's disease.

Dual GSK-3β/AChE Inhibitors as a New Strategy for Multitargeting Anti-Alzheimer's Disease Drug Discovery.

Tumor-specific activated photodynamic therapy with an oxidation-regulated strategy for enhancing anti-tumor efficacy.