Challenges in the study of self-assembled aggregates in decoction of traditional Chinese medicine: A preliminary review / 药学学报

Decoction is the most commonly used dosage form in the clinical treatment of traditional Chinese medicine (TCM). During boiling, the violent movement of various active ingredients in TCM creates molecular forces such as hydrogen bonding, π-π stacking, hydrophobic interactions and electrostatic interactions, which results in the formation of self-assembled aggregates in decoction (SADs), including particles, gels, fibers, etc. It was found that SADs widely existed in decoction with biological activities superior to both effective monomers and their physical mixtures, providing a new idea to reveal the pharmacodynamic material basis of Chinese herbal medicine from the perspective of component interactions-phase structure. Recently, SADs have become a novel focus of research in TCM. This paper reviewed their relevant studies in recent years and found some issues to be concerned in the research, such as the polydispersity of decoction system, instability of active ingredient interactions during boiling, uncertainty of the aggregates self-assembly rules, and stability, purity, yield of the products. In this regard, some solutions and new ideas were presented for the integrated development and clinical application of SADs.

Dual-responsive supramolecular photodynamic nanomedicine with activatable immunomodulation for enhanced antitumor therapy

A major challenge facing photodynamic therapy (PDT) is that the activity of the immune-induced infiltrating CD8+ T cells is subject to the regulatory T lymphocytes (Tregs), leaving the tumor at risk of recurrence and metastasis after the initial ablation. To augment the antitumor response and reprogram the immunosuppressive tumor microenvironment (TME), a supramolecular photodynamic nanoparticle (DACss) is constructed by the host-guest interaction between demethylcantharidin-conjugated β-cyclodextrin (DMC-CD) and amantadine-terminated disulfide-conjugated FFVLGGGC peptide with chlorin e6 decoration (Ad-ss-pep-Ce6) to achieve intelligent delivery of photosensitizer and immunomodulator for breast cancer treatment. The acid-labile β-carboxamide bond of DMC-CD is hydrolyzed in response to the acidic TME, resulting in the localized release of DMC and subsequent inhibition of Tregs. The guest molecule Ad-ss-pep-Ce6 can be cleaved by a high level of intracellular GSH, reducing photosensitizer toxicity and increasing photosensitizer retention in the tumor. With a significant increase in the CTL/Treg ratio, the combination of Ce6-based PDT and DMC-mediated immunomodulation adequately achieved spatiotemporal regulation and remodeling of the TME, as well as improved primary tumor and in situ lung metastasis suppression with the aid of PD-1 antibody.

Intermittent Theta Burst Stimulation Attenuates Cognitive Deficits and Alzheimer's Disease-Type Pathologies via ISCA1-Mediated Mitochondrial Modulation in APP/PS1 Mice / 神经科学通报·英文版

Intermittent theta burst stimulation (iTBS), a time-saving and cost-effective repetitive transcranial magnetic stimulation regime, has been shown to improve cognition in patients with Alzheimer's disease (AD). However, the specific mechanism underlying iTBS-induced cognitive enhancement remains unknown. Previous studies suggested that mitochondrial functions are modulated by magnetic stimulation. Here, we showed that iTBS upregulates the expression of iron-sulfur cluster assembly 1 (ISCA1, an essential regulatory factor for mitochondrial respiration) in the brain of APP/PS1 mice. In vivo and in vitro studies revealed that iTBS modulates mitochondrial iron-sulfur cluster assembly to facilitate mitochondrial respiration and function, which is required for ISCA1. Moreover, iTBS rescues cognitive decline and attenuates AD-type pathologies in APP/PS1 mice. The present study uncovers a novel mechanism by which iTBS modulates mitochondrial respiration and function via ISCA1-mediated iron-sulfur cluster assembly to alleviate cognitive impairments and pathologies in AD. We provide the mechanistic target of iTBS that warrants its therapeutic potential for AD patients.

Composition and spatio-temporal dynamics of aquatic bird community in humid areas of Alto Parana Atlantic Forest

Abstract The northwestern portion of the Upper Paraná Atlantic Forest ecoregion is one of the most disturbed and fragmented areas in the Atlantic Forest, and little is known about the local avifauna. In this study, we have described the composition and diversity of the aquatic avifauna of this region and analyzed the patterns of similarity with respect to the seasonal as well as spatial distribution. We used the line transect sampling technique in six distinct humid areas (including lentic and lotic water bodies) during the dry and rainy seasons of 2012 and 2013. A total of 52 species of waterfowl were recorded. The species richness of the studied areas was surprisingly distinct; only seven waterfowl species, namely Cairina moschata (Linnaeus, 1758), Tigrisoma lineatum (Boddaert, 1783), Rosthramus sociabilis (Vieillot, 1817), Aramus guarauna (Linnaeus, 1766), Vanellus chilensis (Molina, 1782), Jacana jacana (Linnaeus, 1766), and Arundinicola leucocephala (Linnaeus, 1764), were common to these six studied areas. This indicated that the other bird species that were observed might be habitat selective. Moreover, the analysis of the composition of birds in the two seasons (dry and rainy) combined with their spatial distributions showed significant dissimilarities between the areas with lotic (river and constructed wetland) and lentic (lagoons) characteristics. Nevertheless, despite the small extent and low total richness of the entire study area, it was found to be home to 1/3 of all freshwater aquatic birds documented in the state of São Paulo, with the record of 5 migratory species and 11 new species added to the northwest of the state. The heterogeneity of local aquatic environments, habitat selection combined with seasonality, and the absence of other humid locations in the surroundings can explain the diversity and distribution of these birds in the water bodies of this uninvestigated Atlantic Forest ecoregion.

Resumo A porção noroeste da ecorregião Floresta Atlântica do Alto Paraná é uma das mais alteradas e fragmentadas da Mata Atlântica, da qual pouco se sabe sobre a avifauna local. Nosso objetivo foi descrever a diversidade e composição da avifauna aquática, bem como analisar os padrões de similaridade quanto a distribuição temporal e espacial destas aves nesta ecorregião. Utilizamos a transecção linear para amostragem em seis áreas úmidas (corpos dágua lênticos e lóticos), nos períodos de seca e chuva entre 2012 e 2013. Registramos 52 espécies de aves aquáticas e as riquezas das áreas mostraram-se distintas, pois apenas Cairina moschata (Linnaeus, 1758), Tigrisoma lineatum (Boddaert, 1783), Rosthramus sociabilis (Vieillot, 1817), Aramus guarauna (Linnaeus, 1766), Vanellus chilensis (Molina, 1782), Jacana jacana (Linnaeus, 1766), and Arundinicola leucocephala (Linnaeus, 1764) foram comuns às seis áreas, o que indica seleção de habitat. Quando analisada a composição das aves nos dois períodos aliada à distribuição espacial, encontramos dissimilaridades temporais acentuadas entre os ambientes com características lóticas (rio e aterro) e lênticas (lagoas). Isto mostra que, além das diferentes épocas sazonais, é necessário analisar separadamente os diferentes tipos de áreas úmidas. Por fim, apesar da extensão pequena e baixa riqueza total, a área amostrada abrigou 1/3 das aves aquáticas de água doce para o estado de São Paulo, cinco espécies migratórias e 11 novas espécies para o noroeste do estado. A heterogeneidade de ambientes aquáticos locais, forte seleção de habitat aliada à sazonalidade e ausência de outros locais úmidos em seu entorno, explicam a diversidade e distribuição destas aves estreitamente relacionadas aos corpos dágua desta desconhecida ecorregião da Mata Atlântica.

Composition and spatio-temporal dynamics of aquatic bird community in humid areas of Alto Parana Atlantic Forest / Composição e dinâmica espaço-temporal da comunidade de aves aquáticas em áreas úmidas da Floresta Atlântica do Alto Paraná

Abstract The northwestern portion of the Upper Paraná Atlantic Forest ecoregion is one of the most disturbed and fragmented areas in the Atlantic Forest, and little is known about the local avifauna. In this study, we have described the composition and diversity of the aquatic avifauna of this region and analyzed the patterns of similarity with respect to the seasonal as well as spatial distribution. We used the line transect sampling technique in six distinct humid areas (including lentic and lotic water bodies) during the dry and rainy seasons of 2012 and 2013. A total of 52 species of waterfowl were recorded. The species richness of the studied areas was surprisingly distinct; only seven waterfowl species, namely Cairina moschata (Linnaeus, 1758), Tigrisoma lineatum (Boddaert, 1783), Rosthramus sociabilis (Vieillot, 1817), Aramus guarauna (Linnaeus, 1766), Vanellus chilensis (Molina, 1782), Jacana jacana (Linnaeus, 1766), and Arundinicola leucocephala (Linnaeus, 1764), were common to these six studied areas. This indicated that the other bird species that were observed might be habitat selective. Moreover, the analysis of the composition of birds in the two seasons (dry and rainy) combined with their spatial distributions showed significant dissimilarities between the areas with lotic (river and constructed wetland) and lentic (lagoons) characteristics. Nevertheless, despite the small extent and low total richness of the entire study area, it was found to be home to 1/3 of all freshwater aquatic birds documented in the state of São Paulo, with the record of 5 migratory species and 11 new species added to the northwest of the state. The heterogeneity of local aquatic environments, habitat selection combined with seasonality, and the absence of other humid locations in the surroundings can explain the diversity and distribution of these birds in the water bodies of this uninvestigated Atlantic Forest ecoregion.

Resumo A porção noroeste da ecorregião Floresta Atlântica do Alto Paraná é uma das mais alteradas e fragmentadas da Mata Atlântica, da qual pouco se sabe sobre a avifauna local. Nosso objetivo foi descrever a diversidade e composição da avifauna aquática, bem como analisar os padrões de similaridade quanto a distribuição temporal e espacial destas aves nesta ecorregião. Utilizamos a transecção linear para amostragem em seis áreas úmidas (corpos d'água lênticos e lóticos), nos períodos de seca e chuva entre 2012 e 2013. Registramos 52 espécies de aves aquáticas e as riquezas das áreas mostraram-se distintas, pois apenas Cairina moschata (Linnaeus, 1758), Tigrisoma lineatum (Boddaert, 1783), Rosthramus sociabilis (Vieillot, 1817), Aramus guarauna (Linnaeus, 1766), Vanellus chilensis (Molina, 1782), Jacana jacana (Linnaeus, 1766), and Arundinicola leucocephala (Linnaeus, 1764) foram comuns às seis áreas, o que indica seleção de habitat. Quando analisada a composição das aves nos dois períodos aliada à distribuição espacial, encontramos dissimilaridades temporais acentuadas entre os ambientes com características lóticas (rio e aterro) e lênticas (lagoas). Isto mostra que, além das diferentes épocas sazonais, é necessário analisar separadamente os diferentes tipos de áreas úmidas. Por fim, apesar da extensão pequena e baixa riqueza total, a área amostrada abrigou 1/3 das aves aquáticas de água doce para o estado de São Paulo, cinco espécies migratórias e 11 novas espécies para o noroeste do estado. A heterogeneidade de ambientes aquáticos locais, forte seleção de habitat aliada à sazonalidade e ausência de outros locais úmidos em seu entorno, explicam a diversidade e distribuição destas aves estreitamente relacionadas aos corpos d'água desta desconhecida ecorregião da Mata Atlântica.

Report on WFAS 2022 General Assembly and Conference in Singapore / 全日本鍼灸学会雑誌

The World Federation of Acupuncture and Moxibustion (WFAS) General Assembly and International Conference were held online in combination with on-site administration in Singapore on 18th-20th, November 2022. Members of the new Executive Committee (the 10th EC) were elected and future host cities were discussed in the General Assembly. Activities during the 9th EC term including collaboration with the World Health Organization (WHO), activities in the standardization working committee, financial report and proposals from EC members were reviewed in the 9th EC meeting which was held prior to the General Assembly. In the present article, we report the results of the EC meeting and the General Assembly and key topics from the International Conference.

Self-assembled multifunctional nanotheranostics against circulating tumor clusters in metastatic breast cancer

Circulating tumor clusters (CTC) disseminating from the primary tumor are responsible for secondary tumor formation where the conventional treatments such as chemotherapy and radiotherapy does not prevent the metastasis at locally advanced stage of breast cancer. In this study, a smart nanotheranostic system has been developed to track and eliminate the CTCs before it can colonize at a new site, which would reduce metastatic progression and increase the five-year survival rate of the breast cancer patients. Targeted multiresponsive (magnetic hyperthermia and pH) nanomicelles incorporated with NIR fluorescent superparamagnetic iron oxide nanoparticles were developed based on self-assembly for dual modal imaging and dual toxicity for spontaneous killing of CTCs in blood stream. A heterogenous tumor clusters model was developed to mimic the CTCs isolated from breast cancer patients. The nanotheranostic system was further evaluated for the targeting property, drug release kinetics, hyperthermia and cytotoxicity against developed CTC model in vitro. In vivo model in BALB/c mice equivalent to stage III and IV human metastatic breast cancer was developed to evaluate the biodistribution and therapeutic efficacy of micellar nanotheranostic system. Reduced CTCs in blood stream and low distant organ metastasis after treatment with the nanotheranostic system demonstrates its potential to capture and kill the CTCs that minimize the secondary tumor formation at distant sites.

Buzhong Yiqitang Reduces CIH-induced Pulmonary Inflammatory Injury by ACE2-Ang（1-7）-Mas Axis / 中国实验方剂学杂志

ObjectiveTo investigate the intervention effect of Buzhong Yiqitang （BZYQT） on pulmonary inflammation in mice induced by chronic intermittent hypoxia （CIH） and preliminarily elucidate its mechanism. MethodForty healthy male C57BL/6 mice aged 6-8 weeks were randomly divided into the following groups： normoxia group， model group （exposed to CIH）， and low-， medium-， and high-dose BZYQT groups. The normoxia group was exposed to a normoxic environment， while the model group and the low-， medium-， and high-dose BZYQT groups were exposed to intermittent hypoxia. In the BZYQT groups， the BZYQT （8.1， 16.2， 32.4 g·kg-1·d-1） was administered orally 30 min before placing the mice in the hypoxic chamber， while the model group and the normoxia group received an equivalent volume of normal saline. After five weeks of modeling， pulmonary function of the mice was measured using an EMKA animal lung function analyzer， and lung tissue samples were collected after the pulmonary function tests. Hematoxylin-eosin （HE） staining was performed to observe the histopathological changes in the lung tissue of each group. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of interleukin-6 （IL-6）， interleukin-8 （IL-8）， tumor necrosis factor-α （TNF-α） in the serum， as well as angiotensin Ⅱ （Ang Ⅱ） and angiotensin-（1-7） ［Ang（1-7）］ in lung tissue. Western blot and immunohistochemistry were used to detect the protein expression of IL-6， IL-8， TNF-α， angiotensin-converting enzyme 2 （ACE2）， and mitochondrial assembly receptor （Mas）. ResultCompared with the normoxia group， the model group showed significant abnormalities in lung function （P<0.05， P<0.01）， lung tissue changes， such as thickening of alveolar walls and inflammatory cell infiltration， increased levels of IL-6， IL-8， TNF-α in the serum and Ang Ⅱ in lung tissue （P<0.01）， decreased level of Ang（1-7） （P<0.01）， increased protein expression of IL-6， IL-8， and TNF-α， and decreased protein expression of ACE2 and Mas （P<0.05， P<0.01）. Compared with the model group， the BZYQT groups showed improvement in lung function （P<0.05， P<0.01）， and HE staining of lung tissue showed approximately normal alveolar wall thickness and reduced inflammatory cell infiltration. Immunohistochemistry and Western blot analysis showed a significant decrease in the expression of inflammatory-related proteins （P<0.05， P<0.01）， and a significant increase in ACE2 and Mas protein expression （P<0.05， P<0.01）. ConclusionBZYQT can improve lung injury in mice exposed to CIH by regulating the ACE2-Ang（1-7）-Mas axis to inhibit inflammatory responses.

REEP1 Preserves Motor Function in SOD1G93A Mice by Improving Mitochondrial Function via Interaction with NDUFA4 / 神经科学通报·英文版

A decline in the activities of oxidative phosphorylation (OXPHOS) complexes has been consistently reported in amyotrophic lateral sclerosis (ALS) patients and animal models of ALS, although the underlying molecular mechanisms are still elusive. Here, we report that receptor expression enhancing protein 1 (REEP1) acts as an important regulator of complex IV assembly, which is pivotal to preserving motor neurons in SOD1G93A mice. We found the expression of REEP1 was greatly reduced in transgenic SOD1G93A mice with ALS. Moreover, forced expression of REEP1 in the spinal cord extended the lifespan, decelerated symptom progression, and improved the motor performance of SOD1G93A mice. The neuromuscular synaptic loss, gliosis, and even motor neuron loss in SOD1G93A mice were alleviated by increased REEP1 through augmentation of mitochondrial function. Mechanistically, REEP1 associates with NDUFA4, and plays an important role in preserving the integrity of mitochondrial complex IV. Our findings offer insights into the pathogenic mechanism of REEP1 deficiency in neurodegenerative diseases and suggest a new therapeutic target for ALS.

Research progress of microparticles in traditional Chinese medicine decoction / 药学学报

Decoction is a classical dosage form of traditional Chinese medicines. In the process of decocting, various complex components produce physical interactions and chemical reactions, among which physical interactions include van der Waals force, hydrogen bond, electrostatic interaction, π-π stacking, etc., and chemical reactions include Maillard reaction, oxidation reaction, hydrolysis reaction, degradation reaction, polymerization reaction, etc. New substances and original ingredients from chemical reactions can be further activated. These effects form the basis of particle formation in the broth. The sizes of the particles in decoctions range from nanoscale to micron scale, mostly composed of polysaccharide, protein matrix, wrapped in water insoluble molecules, can increase the dispersion of insoluble components and the stability of unstable components, as well as reduce the volatile components and toxic components of volatile components, and ultimately achieve the purpose of efficient absorption and toxicity reduction. From the angle of physical change and chemical reaction in the process of decoction, this paper expounds the formation mechanism of particles in decoction, expounds the research method of particles, analyzes the components in particles and the interaction between components, and then explains the pharmacodynamic characteristics of traditional Chinese medicine decoction, which provides the foundation for the modernization of Chinese decoction.

Advance on small molecule self-assembled nano-drug delivery system / 药学学报

Since the application of biomedical nanotechnology in the field of drug delivery breathes new life into the research and development of high-end innovative agents, a substantial number of novel nano-drug delivery systems (nano-DDSs) have been successively developed and applied in the clinical practice. Among them, small molecule pure drug and prodrug-based nanoassemblies have grasped great attention, owing to the facile fabrication, ultrahigh drug loading and feasible industrial production. Herein, we provide an overview on the latest updates of small-molecule nanoassemblies. Firstly, the self-assembled prodrug-based nano-DDSs are introduced, including nanoassemblies formed by amphiphilic monomeric prodrugs, hydrophobic monomeric prodrugs and dimer monomeric prodrugs. Then, the recent advances on nanoassemblies of small molecule pure chemical drugs and biological drugs are presented. Furthermore, carrier-free small-molecule hybrid nanoassemblies of pure drugs and/or prodrugs are summarized and analyzed. Finally, the rational design, application prospects and clinical challenges of small-molecule self-assembled nano-DDSs are discussed and highlighted. This review aims to provide scientific reference for constructing the next generation of nanomedicines.

Application of self-assembly in polypeptide drugs: a review / 生物工程学报

Self-assembly refers to the spontaneous process where basic units such as molecules and nanostructured materials form a stable and compact structure. Peptides can self-assemble by non-covalent driving forces to form various morphologies such as nanofibers, nano layered structures, and micelles. Peptide self-assembly technology has become a hot research topic in recent years due to the advantages of definite amino acid sequences, easy synthesis and design of peptides. It has been shown that the self-assembly design of certain peptide drugs or the use of self-assembled peptide materials as carriers for drug delivery can solve the problems such as short half-life, poor water solubility and poor penetration due to physiological barrier. This review summarizes the formation mechanism of self-assembled peptides, self-assembly morphology, influencing factors, self-assembly design methods and major applications in biomedical field, providing a reference for the efficient use of peptides.

Separation, characterization, and antiviral activity of colloidal phase state of Maxing Shigan Decoction / 中国中药杂志

This study focused on the separation, characterization, content determination, and antiviral efficacy research on colloidal particles with different sizes in Maxing Shigan Decoction(MXSG). The mixed colloidal phase of MXSG was initially separated into small colloidal particle segment(S), medium colloidal particle segment(M), and big colloidal particle segment(B) using ultrafiltration. Further fine separation was performed using size-exclusion chromatography. Dynamic light scattering(DLS) and transmission electron microscopy(TEM) were employed to characterize the size and morphology of the separated colloidal particles. UPLC-MS/MS was used to determine the content of ephedrine, amygdalin, glycyrrhizic acid, and the EDTA complexometric titration was used to measure the calcium(Ca~(2+)) content in different colloidal phases. Finally, a respiratory syncytial virus(RSV) infection mouse model was established using intranasal administration. The experimental groups included a blank group, a model group, a ribavirin group, an MXSG group, an S group, an M group, and a B group. Oral administration was given for treatment, and pathological changes in mouse lung tissue and organ indices were evaluated. The results of the study showed that the distribution of ephedrine, amygdalin, glycyrrhizic acid, and Ca~(2+) content was not uniform among different colloidal segments. Among them, the B segment had the highest proportions of the three components, except for Ca~(2+), accounting for 46.35%, 53.72%, and 92.36%, respectively. Size-exclusion chromatography separated colloidal particles with uniform morphology in the size range of 100-500 nm. Compared to the S and M segments, the B segment showed an increased lung index inhibition rate(38.31%), spleen index, and thymus index in RSV-infected mice, and it improved the infiltration of inflammatory cells and lung injury in the lung tissue of mice. The complex components in MXSG form colloidal particles of various sizes and morphologies through heating, and small-molecule active components such as ephedrine, amygdalin, glycyrrhizic acid, and Ca~(2+) participate in the assembly to varying degrees. The main material basis for the antiviral effect of MXSG is the colloidal particles with certain particle sizes formed by the assembly of active components during the heating process.

Icaritin and pyropheophorbide-a self-assembled nanomedicine for enhanced the efficacy of photodynamic tumor therapy by increase the cell autophagy / 药学学报

Autophagy often occurs after cells are attacked by oxidative stress, where damaged structures are phagocytic and degraded into nutrients, thereby reducing oxidative damage, promoting the survival of cancer cells and reducing the therapeutic effect of photodynamic therapy (PDT). However, excessive activation of autophagy can promote cell apoptosis. In this paper, the photosensitizer pyropheophorbide-a (Ppa) was used to produce a large amount of reactive oxygen species (ROS) to achieve the effect of killing cancer cells. At the same time, icaritin (Ica), an autophagy inducer, was used to over-activate autophagy, which transformed the protection of cancer cells into the promotion of cancer cell apoptosis, so as to improve the effect of photodynamic therapy. In this study, the interaction force between Ica and Ppa was exploited to successfully construct a self-assembled nanomedicine IP with good stability and high drug load. The synthesis method is simple, through using the drug itself as a carrier, and the loading capacity (LA) of Ica and Ppa can be increased to 83.53% and 16.45% without introducing potential biosafety risks of nanocarriers. Compared with free Ppa, self-assembled nanomedicine IP showed superior performance in cellular uptake and reactive oxygen species production. In addition, the self-assembled nanomedicine IP can reverse the protective autophagy induced by PDT by activating the autophagy of tumor cells, and facilitate apoptosis and antitumor coordination, which significantly improves the antitumor activity of PDT.

Application of Self-assembled Nano-strategies of Traditional Chinese Medicine in Tumor Therapy： A Review / 中国实验方剂学杂志

Chinese medicine self-assembly nano-strategies（CSAN） is to utilize the self-assembly property of Chinese medicine components， so that the Chinese medicine components can self-assemble to form structurally stable nano-preparations through non-covalent interactions. The formation of Chinese medicine self-assembly nano-preparations is often a synergistic result of a variety of non-covalent interactions， and many Chinese medicine monomers are susceptible to self-assembly due to their structural characteristics， and the phenomenon of self-assembly of Chinese medicine is also common in the decoction of single or compound Chinese medicine， which has attracted the attention of researchers. It is found that CSAN can improve the solubility and bioavailability of active components in Chinese medicine， which is of positive significance for the development and application of insoluble components of Chinese medicine. The self-assembly phenomenon of Chinese medicine decoction is closely related to the therapeutic efficacy， and the study of self-assembly phenomenon of Chinese medicine will bring a new perspective for the explanation of the mechanism of Chinese medicine decoction. At the same time， traditional Chinese medicine（TCM） has unique advantages in the field of anti-tumor. The application of CSAN in the field of oncology can not only exert the anti-tumor effect of the active components of Chinese medicine directly， but also act as a natural nano-carrier to carry chemotherapy drugs for combination chemotherapy， improve the targeting of drugs， enhance the anti-tumor efficacy， and reduce the side effects of chemotherapy， which has excellent anti-tumor potential. The preparation method of Chinese medicine self-assembly nano-preparations is simple， low cost， and has better safety than traditional nano-preparations， which is conducive to the promotion of the clinical transformation of nano-preparations， and also helps to provide new strategies and perspectives for promoting the modernization of TCM. Therefore， based on a large number of researches in this field in recent years， this paper reviewed the formation mechanism， different assembly forms， formation conditions and stability of Chinese medicine self-assembly nano-preparations by searching databases such as China national knowledge infrastructure（CNKI）， PubMed， WanFang data and VIP， and summarized the application of CSAN in different tumor therapies， providing a reference for further research on CSAN.

Effects of ferrocene position isomerization on the self-assembly behavior and antibacterial effect of coupled cationic peptides / 中国药房

OBJECTIVE To design the two isomers of ferrocene （Fc）-coupled cationic peptides （hereinafter referred to as “peptides”） [Fc-K（C8）FFHK and C8-K（Fc） FFHK] and the control peptide [C8-K（C8）FFHK]， and to explore the effects of Fc position isomerization on the self-assembly behavior and antibacterial effect of peptides. METHODS All isomerized peptides were prepared by standard solid-phase synthesis and purified by reversed-phase high-performance liquid chromatography. The stability of the peptide was analyzed by using UV spectrophotometry to detect UV absorption spectra， and Zeta potential analyzer to determine Zeta potential. The secondary structure was characterized by circular dichroism spectrum （CD）， Fourier transform infrared spectrometer （FTIR）， thioflavin T （ThT） fluorescence spectrum and transmission electron microscopy （TEM）. The differences in antibacterial activity and biocompatibility of the 2 kinds of isomerized peptides were evaluated by in vitro reactive oxygen species （ROS） generation test， growth curve determination test， plate method， cytotoxicity assay and hemolysis test. RESULTS Three peptides with purity higher than 95% were synthesized. The stability test results showed that the UV absorption spectra of Fc-K（C8）FFHK and C8-K（Fc）FFHK remained almost unchanged when placed at room temperature for 24 and 96 hours， and their Zeta potential were decreased by 0.3 mV and 0.5 mV， respectively. Secondary structure characterization results showed that Fc-K（C8）FFHK and C8-K（Fc）FFHK were self-assembled to form twisted nanoribbons and short nanofibers， respectively； C8-K（C8）FFHK was assembled into cylindrical nanofibers. The optical spectrum results showed that there were certain differences in the content of structures such as β-sheet and α-helix. The in vitro ROS generation test results showed that ROS generation efficiency of Fc-K（C8）FFHK at pH 6.0 was higher than C8-K（Fc）FFHK. The results of in vitro antibacterial activity showed that for methicillin-resistant Staphylococcus aureus， both the isomeric peptides had similar minimum inhibitory concentration （MIC） values of 50 μg/mL which were far lower than the control peptide （400 μg/mL）. To Escherichia coli， Fc-K（C8）FFHK had better antibacterial activity than C8-K（Fc）FFHK. Finally， cytotoxicity assay and hemolysis test results showed that both isomeric peptides had good biocompatibility. CONCLUSIONS By wangjingwen8021@163.com coupling Fc， the antibacterial activity of cationic self-assembled peptides can be improved. Regulating the position of Fc in the peptide sequence could regulate the self-assembly behavior and antibacterial effect of the self-assembled peptides.

Research progress on linear ubiquitin chain assembly complex and OTU deubiquitinase with linear linkage specificity in tumor / 药学实践杂志

Linear ubiquitination is an important post-translational modification that has been discovered in recent years. The linear ubiquitin chain is formed by the linkage of glycine residue of one ubiquitin protein to the methionine residue of another ubiquitin. This process is regulated by the linear ubiquitin chain assembly complex (LUBAC) and the OTU deubiquitinase with linear linkage specificity (OTULIN). Linear ubiquitination is involved in various biological processes, including immune response, inflammation, and cell apoptosis. Recent studies have shown that linear ubiquitination is closely related to the occurrence, development, and drug resistance of tumors by affecting signaling pathways such as NF-κB and Wnt/β-catenin. The research progress on the function of LUBAC and OTULIN in tumors was reviewed in this paper.

Research progress of enzyme-instructed self-assembly molecules for tumor therapy and imaging / 中国药科大学学报

@#Self-assembly is the basis of the formation of biological macromolecular structure. Enzyme-instructed self-assembly (EISA) with the help of tool enzymes, realizing the conversion of small molecular compounds to supramolecular nanostructures at specific sites, become a new strategy for drug discovery.In recent years, the exploration of EISA for developing malignant cancer therapy and imaging has made considerable progress, achieving the precise regulation and tumor targeting of nanostructures. This paper reviews the latest progress of EISA in the field of tumor diagnosis and treatment, the functions and characteristics of tool enzymes such as alkaline phosphatase, sirtuin, tyrosinase, γ-glutamyltranspeptidase and caspase-3,summarizes the research status of EISA targeting multiple organelles in tumor therapy, and introduces the application of EISA in tumor imaging, aiming to provide reference forthe research of EISA strategy in tumor diagnosis and treatment.

Membrane dual-targeting probes: A promising strategy for fluorescence-guided prostate cancer surgery and lymph node metastases detection

Fluorescence-guided surgery (FGS) with tumor-targeted imaging agents, particularly those using the near-infrared wavelength, has emerged as a real-time technique to highlight the tumor location and margins during a surgical procedure. For accurate visualization of prostate cancer (PCa) boundary and lymphatic metastasis, we developed a new approach involving an efficient self-quenched near-infrared fluorescence probe, Cy-KUE-OA, with dual PCa-membrane affinity. Cy-KUE-OA specifically targeted the prostate-specific membrane antigen (PSMA), anchored into the phospholipids of the cell membrane of PCa cells and consequently showed a strong Cy7-de-quenching effect. This dual-membrane-targeting probe allowed us to detect PSMA-expressing PCa cells both in vitro and in vivo and enabled clear visualization of the tumor boundary during fluorescence-guided laparoscopic surgery in PCa mouse models. Furthermore, the high PCa preference of Cy-KUE-OA was confirmed on surgically resected patient specimens of healthy tissues, PCa, and lymph node metastases. Taken together, our results serve as a bridge between preclinical and clinical research in FGS of PCa and lay a solid foundation for further clinical research.

Photosensitive pro-drug nanoassemblies harboring a chemotherapeutic dormancy function potentiates cancer immunotherapy

Immunotherapy combined with effective therapeutics such as chemotherapy and photodynamic therapy have been shown to be a successful strategy to activate anti-tumor immune responses for improved anticancer treatment. However, developing multifunctional biodegradable, biocompatible, low-toxic but highly efficient, and clinically available transformed nano-immunostimulants remains a challenge and is in great demand. Herein, we report and design of a novel carrier-free photo-chemotherapeutic nano-prodrug COS-BA/Ce6 NPs by combining three multifunctional components-a self-assembled natural small molecule betulinic acid (BA), a water-soluble chitosan oligosaccharide (COS), and a low toxic photosensitizer chlorin e6 (Ce6)-to augment the antitumor efficacy of the immune adjuvant anti-PD-L1-mediated cancer immunotherapy. We show that the designed nanodrugs harbored a smart and distinctive "dormancy" characteristic in chemotherapeutic effect with desired lower cytotoxicity, and multiple favorable therapeutic features including improved 1O2 generation induced by the reduced energy gap of Ce6, pH-responsiveness, good biodegradability, and biocompatibility, ensuring a highly efficient, synergistic photochemotherapy. Moreover, when combined with anti-PD-L1 therapy, both nano-coassembly based chemotherapy and chemotherapy/photodynamic therapy (PDT) could effectively activate antitumor immunity when treating primary or distant tumors, opening up potentially attractive possibilities for clinical immunotherapy.