scBlood: A comprehensive single-cell accessible chromatin database of blood cells.

The advent of single cell transposase-accessible chromatin sequencing (scATAC-seq) technology enables us to explore the genomic characteristics and chromatin accessibility of blood cells at the single-cell level. To fully make sense of the roles and regulatory complexities of blood cells, it is critical to collect and analyze these rapidly accumulating scATAC-seq datasets at a system level. Here, we present scBlood (https://bio.liclab.net/scBlood/), a comprehensive single-cell accessible chromatin database of blood cells. The current version of scBlood catalogs 770,907 blood cells and 452,247 non-blood cells from ∼400 high-quality scATAC-seq samples covering 30 tissues and 21 disease types. All data hosted on scBlood have undergone preprocessing from raw fastq files and multiple standards of quality control. Furthermore, we conducted comprehensive downstream analyses, including multi-sample integration analysis, cell clustering and annotation, differential chromatin accessibility analysis, functional enrichment analysis, co-accessibility analysis, gene activity score calculation, and transcription factor (TF) enrichment analysis. In summary, scBlood provides a user-friendly interface for searching, browsing, analyzing, visualizing, and downloading scATAC-seq data of interest. This platform facilitates insights into the functions and regulatory mechanisms of blood cells, as well as their involvement in blood-related diseases.

[Metabolomics of quality formation of different cultivars of Peucedanum praeruptorum].

This study aims to reveal the quality formation of different cultivars of Peucedanum praeruptorum based on the metabolic differences and provide a theoretical basis for the development and utilization of this medicinal herb. The non-target metabonomics analysis based on ultra-high performance liquid chromatography tandem mass spectrometry(UHPLC-MS/MS) was conducted for six cultivars(YS, H, LZ, LY, LX, and Z) of P. praeruptorum of the same origin and at the same development stage. The principal component analysis, orthogonal partial least squares discriminant analysis, and univariate statistical analysis were carried out to screen the differential metabolites of different cultivars. The potential biomarkers associated with quality formation were predicted based on the mass-to-charge ratio, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, information of relevant literature, and correlation analysis. The results showed that metabolites differed significantly among the six cultivars, and 571 and 465 differential metabolites were obtained in the positive and negative ion modes, respectively. From the differential metabolites, 22 potential biomarkers related to quality formation were predicted, which involved 9 metabolic pathways, including phenylalanine, tyrosine and tryptophan biosynthesis, biosynthesis of phenylpropanoids, and biosynthesis of plant hormones. Compared with the YS cultivar, other cultivars showed decreased concentrations of psoralen, imperatorin, and luvangetin and increased concentrations of 7-hydroxycoumarine, esculetin, columbianetin, and jasmonic acid, which were involved in the biosynthesis of phenylpropanoids. The concentrations of 2-succinylbenzoate, heraclenol, and L-tyrosine involved in other metabolic pathways decreased, especially in the Z and H cultivars. Therefore, regulating the biosynthesis of phenylpropanoids is one of the key mechanisms for improving the cultivar quality of P. praeruptorum. The Z and H cultivars have better quality and metabolic processes than other cultivars and thus can be used for the screening and breeding of high-quality germplasm.

Protoberberine alkaloids: A review of the gastroprotective effects, pharmacokinetics, and toxicity.

BACKGROUND: Stomach diseases have become global health concerns. Protoberberine alkaloids (PBAs) are a group of quaternary isoquinoline alkaloids from abundant natural sources and have been shown to improve gastric disorders in preclinical and clinical studies. The finding that PBAs exhibit low oral bioavailability but potent pharmacological activity has attracted great interest. PURPOSE: This review aims to provide a systematic review of the molecular mechanisms of PBAs in the treatment of gastric disorders and to discuss the current understanding of the pharmacokinetics and toxicity of PBAs. METHODS: The articles related to PBAs were collected from the Web of Science, Pubmed, and China National Knowledge Infrastructure databases using relevant keywords. The collected articles were screened and categorized according to their research content to focus on the gastroprotective effects, pharmacokinetics, and toxicity of PBAs. RESULTS: Based on the results of preclinical studies, PBAs have demonstrated therapeutic effects on chronic atrophic gastritis and gastric cancer by activating interleukin-4 (IL-4)/signal transducer and activator of transcription 6 (STAT6) pathway and suppressing transforming growth factor-beta 1 (TGF-ß1)/phosphoinositide 3-kinase (PI3K), Janus kinase-2 (JAK2)/signal transducers and activators of transcription 3 (STAT3), and mitogen-activated protein kinase (MAPK) pathways. The major PBAs exhibit similar pharmacokinetic properties, including rapid absorption, slow elimination, and low bioavailability. Notably, the natural organ-targeting property of PBAs may account for the finding of their low blood levels and high pharmacological activity. PBAs interact with other compounds, including conventional drugs and natural products, by modulation of metabolic enzymes and transporters. The potential tissue toxicity of PBAs should be emphasized due to their high tissue accumulation. CONCLUSION: This review highlights the gastroprotective effects, pharmacokinetics, and toxicity of PBAs and will contribute to the evaluation of drug properties and clinical translational studies of PBAs, accelerating their transfer from the laboratory to the bedside.

scATAC-Ref: a reference of scATAC-seq with known cell labels in multiple species.

Chromatin accessibility profiles at single cell resolution can reveal cell type-specific regulatory programs, help dissect highly specialized cell functions and trace cell origin and evolution. Accurate cell type assignment is critical for effectively gaining biological and pathological insights, but is difficult in scATAC-seq. Hence, by extensively reviewing the literature, we designed scATAC-Ref (https://bio.liclab.net/scATAC-Ref/), a manually curated scATAC-seq database aimed at providing a comprehensive, high-quality source of chromatin accessibility profiles with known cell labels across broad cell types. Currently, scATAC-Ref comprises 1 694 372 cells with known cell labels, across various biological conditions, >400 cell/tissue types and five species. We used uniform system environment and software parameters to perform comprehensive downstream analysis on these chromatin accessibility profiles with known labels, including gene activity score, TF enrichment score, differential chromatin accessibility regions, pathway/GO term enrichment analysis and co-accessibility interactions. The scATAC-Ref also provided a user-friendly interface to query, browse and visualize cell types of interest, thereby providing a valuable resource for exploring epigenetic regulation in different tissues and cell types.

The differences in plant invasion in two types of shorelines under flow regulation of the Three Gorges Reservoir.

Riparian zones, crucial for linking fluvial and terrestrial habitats, are among the most diverse ecosystems. However, they are intensively invaded by alien plants, particularly in dam-regulated rivers. Therefore, understanding the mechanisms underlying plant invasion in dam-regulated river systems has become increasingly important, given that over two-thirds of global rivers are artificially regulated. Regulated rivers may flood upland areas or pristine riparian zones, resulting in shorelines developed from pre-upland and pre-riparian areas. However, differences in invasion intensities, adaptive strategies of invasive plants, and native species' resistance (namely the diversity-invasibility relationship) across these shorelines are unclear. To address these uncertainties, we performed field investigations in the Three Gorges Reservoir (TGR) on the upper Yangtze River, where both pre-upland and pre-riparian shorelines are present. Our findings indicate that pre-upland shorelines are more intensively invaded, showing higher relative richness and cover of invasive species. Invasive plants in this area displayed more conservative resource strategies and greater drought tolerance, exhibiting lower community-weighted mean (CWM) specific leaf area, higher CWM leaf dry mass content, and larger CWM seed mass. Pre-upland shorelines' invasibility decreased as the richness and cover of native species increased, a trend not observed in pre-riparian shorelines. The observed variations in plant invasion between the two shoreline types are primarily driven by differences in resident plant presence, soil moisture levels, and hydrological disturbances. This study provides valuable insights for policymakers and practitioners involved in managing invasive plants in regulated river ecosystems.

Responses of dry matter accumulation and partitioning to drought and subsequent rewatering at different growth stages of maize in Northeast China.

Introduction: Dry matter accumulation (DMA) and dry matter partitioning (DMP) are important physiological processes determining crop yield formation. Deep understanding of the DMA and DMP processes and their responses to drought are limited by difficulty in acquiring total root biomass. Methods: Pot experiments with treatments quitting and ceasing ear growth (QC) and controlling soil water (WC) during vegetative (VP) and reproductive (RP) growth stages of maize (Zea mays) were conducted in Jinzhou in 2019 and 2020 to investigate the effects of drought and rewatering on DMW and DMP of different organs. Results: The response of DMW of reproductive organ to drought was more sensitive than those of vegetative organs, and was maintained after rehydration. Drought during VP (VPWC) reduced more sharply DMW of stalk than of leaves, and that during RP (RPWC) decreased more substantially leaves DMW. The effect of drought on DMPR was inconsistent with that on DMW for each organ. The DMP patterns of maize in different growth stages have adaptability to some level of water stress, and their responses increased with drought severity. Drought increased significantly DMP rates (DMPRs) of vegetative organs and reduced the ear DMPR and harvest index (HI), attributing to the suppressed photosynthates partitioning into ear and dry matter redistribution (DMRD) of vegetative organs, especially for stalk DMRD decreasing 26%. The persistence of drought impact was related to its occurrence stage and degree as well as the duration during rewatering to maturity. The aftereffect of drought during different growth periods on DMP were various, and that of VPWC enlarged and drastically induced the reduction of HI, also was larger than that of RPWC which demonstrated obvious alleviation in the previous responses of DMP and HI. Root-shoot ratio (RSR) increased under VPWC and RPWC and subsequent rehydration. Discussion: The DMWs of stalk, roots and leaves were affected by VPWC in order from large to small, and were close to or larger than the controls after rehydration, indicating the compensation effect of rewatering after drought. The DMPRs, RSR AND HI are the important parameters in agricultural production, and are often used as the constants, but in fact they vary with plant growth. In addition, the interannual differences in ear and stalk DMPRs in response to drought were probably caused by the difference in degree and occurrence stage of drought, further reflecting the variation in response of allometry growth among organs to the environment. Besides, the persistence of drought impact was related to the occurrence stage and degree of drought, which is also associated with the duration during rewatering to maturity. Notably, the effect of drought on DMW was inconsistent with that on DMPR for each organ meaning that the two variables should be discussed separately. The QC did not affect total DMW but increased RSR, changed and intensified the effect and aftereffect of RPWC on DMP, respectively, indicating that the DMP pattern and its response to drought occur change under the condition of QC.

Comparative systematic review and meta-analysis of the therapeutic effects of coblation tonsillectomy versus electrocautery tonsillectomy.

BACKGROUND: Surgical removal of the primary lesion is a common treatment for chronic tonsillitis, recurrent tonsillitis, and tonsillar hypertrophy, and is the most widely performed surgery in otorhinolaryngology. With the development and progress of medical science and technology, the methods of tonsillectomy have gradually diversified, and it is of great significance to seek the best tonsillectomy method. This meta-analysis explored the advantages and disadvantages of coblation tonsillectomy (CT) and electrocautery tonsillectomy (ET). METHODS: The keywords "coblation", "radiofrequency ablation", "electrocautery", and "tonsillectomy" were used to search the PubMed, Embase, Cochrane library, Clinicaltrials.gov, and Google Scholar databases, and randomized controlled trials (RCTs) of the 2 procedures since the establishment of the database were included. After screening and bias risk assessment, a meta-analysis was performed using Stata 16.0 software. RESULTS: A total of 10 articles met the inclusion criteria and entered the final meta-analysis. There were 1,056 participants, including 547 patients who underwent CT and 509 patients who underwent ET. There was no significant difference in the operation time between CT and ET [standard mean difference (SMD) =0.39, 95% CI: -0.35 to 1.13, Z=1.044, P=0.296]. CT resulted in less intraoperative blood loss than ET (SMD =-2.62, 95% CI: -4.83 to -0.41, Z=-2.322, P=0.020). The postoperative pain score of CT was less than ET, but the difference was not statistically significant (SMD =-0.28, 95% CI: -0.58 to 0.01, Z=-1.866, P=0.062). CT resulted in less time to return to normal diet after surgery than ET, and the difference was statistically significant (SMD =-0.36, 95% CI: -0.60 to -0.12, Z=-2.918, P=0.004). DISCUSSION: CT resulted in less intraoperative blood loss and faster postoperative recovery than ET, but there was no significant difference in operation time, postoperative pain, and the incidence rate of postoperative complications between the 2 groups.

A new dihydroflavone and a new polyacetylene glucoside from Bidens parviflora.

A new dihydroflavone, 2(S)-isookanin-4'-methoxy-8-O-ß-D-glucopyranoside (1), and a new polyacetylene glucoside, (10S)-tridecane-2E-ene-4,6,8-triyne-1-ol-10-O-ß-D-glucopyranoside (2), along with seven known compounds (3-9), were isolated from the herb of Bidens parviflora Willd. The structures of all the extracted compounds were elucidated by HR-ESI-MS, 1 D and 2 D NMR spectra, as well as circular dichroism (CD).

Small cell carcinoma of the cervix complicated by syndrome of inappropriate antidiuretic hormone secretion: a case report.

Small cell carcinoma of the cervix is a rare malignant tumor in the clinical setting. Clinical manifestations of this tumor are mostly similar to those of normal types of cervical cancer. Small cell carcinoma of the cervix only shows symptoms of neuroendocrine tumors, such as syndrome of inappropriate antidiuretic hormone secretion (SIADH). Most of the hyponatremia caused by SIADH can be managed after removal of the cause. Hyponatremia is a predictor of poor prognosis and can be used as an indicator of partial recurrence. We report a case of small cell carcinoma of the cervix complicated by SIADH. Our patient presented with irregular vaginal bleeding after menopause. After one cycle of chemotherapy, there was trembling of the limbs, and a laboratory examination showed low Na+ and low Cl- levels. After limited water intake, intravenous hypertonic saline, and intermittent diuretic treatment, the patient's blood Na+ levels returned to normal. After a radical operation, the above-mentioned symptoms disappeared.

Enhanced antitumour efficiency of R8GD-modified epirubicin plus tetrandrine liposomes in treatment of gastric cancer via inhibiting tumour metastasis.

Tumour metastasis is a major cause of cancer treatment failure and death, and chemotherapy efficiency for gastric cancer patients is usually unsatisfactory due to tumour cell metastasis, poor targeting and serious adverse reactions. In this study, a kind of R8GD-modified epirubicin plus tetrandrine liposomes was prepared to enhance the antitumor efficiency via killing tumour cells, destroying tumour metastasis and inhibiting energy supply for tumour cells. In order to investigate the antitumour efficiency of the targeting liposomes, morphology observation, intracellular uptake, cytotoxic effects, and inhibition on tumour metastasis and energy supply were carried out in vitro, and tumour-bearing mice models were established to investigate the antitumour efficiency in vivo. In vitro results showed that R8GD-modified epirubicin plus tetrandrine liposomes with ideal physicochemical properties could kill the most tumour cells, inhibit tumour metastasis and cut-off energy supply for tumour cells. In vivo results exhibited that R8GD-modified epirubicin plus tetrandrine liposomes could enhance the accumulation in tumour site and display an obvious antitumor efficiency. Therefore, R8GD-modified epirubicin plus tetrandrine liposomes could be used as a potential therapy for treatment of gastric cancer.

Enhanced antitumour efficacy of functionalized doxorubicin plus schisandrin B co-delivery liposomes via inhibiting epithelial-mesenchymal transition.

Non-small cell lung cancer (NSCLC) is a malignant cancer characterized by easy invasion, metastasis and poor prognosis, so that conventional chemotherapy cannot inhibit its invasion and metastasis. Doxorubicin (DOX), as a broad-spectrum antitumour drug, cannot be widely used in clinic because of its poor targeting, short half-life, strong toxicity and side effects. Therefore, the aim of our study is to construct a kind of PFV modified DOX plus schisandrin B liposomes to solve the above problems, and to explore its potential mechanism of inhibiting NSCLC invasion and metastasis. The antitumour efficiency of the targeting liposomes was carried out by cytotoxicity, heating ablation, wound healing, transwell, vasculogenic mimicry channels formation and metastasis-related protein tests in vitro. Pharmacodynamics were evaluated by tumour inhibition rate, HE staining and TUNEL test in vivo. The enhanced anti-metastatic mechanism of the targeting liposomes was attributed to the downregulation of vimentin, vascular endothelial growth factor, matrix metalloproteinase 9 and upregulation of E-cadherin. In conclusion, the PFV modified DOX plus schisandrin B liposomes prepared in this study provided a treatment strategy with high efficiency for NSCLC.

Curcumin prevents renal cell apoptosis in acute kidney injury in a rat model of dry-heat environment heatstroke via inhibition of the mitochondrial apoptotic pathway.

Heatstroke is a life-threatening illness that is characterised by a core body temperature >40°C and central nervous system dysfunction. Acute kidney injury (AKI) is a common complication of heatstroke, and the mitochondrial apoptotic pathway has been demonstrated to be one of the leading causes of tissue damage and cell death in AKI. Curcumin is a phenol that is extracted from turmeric and demonstrates anti-apoptotic properties. To test if curcumin can protect the kidney from injury caused by heat stress, the effect of curcumin administration on renal injury and apoptosis of renal tissue was examined in a rat model of dry-heat environment. A total of 50 Sprague-Dawley rats were randomly divided into five groups (n=10): Standard temperature control, dry-heat control and curcumin treatment groups (50, 100 and 200 mg/kg groups). After exposure to a dry-heat environment for 150 min, the rats were anesthetized and euthanized. Blood, urine and renal tissue were collected to quantify the expression of specific mitochondrial apoptosis-related molecules. Curcumin pre-treatment decreased blood urea nitrogen and serum creatinine, urinary kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin levels compared with the dry-heat control group. Curcumin was also revealed to downregulate c-Jun N-terminal kinases (JNK), cytochrome c, caspase-3 and caspase-9 expression upon treatment with 100 and 200 mg/kg curcumin, which may result in inhibition of the mitochondrial apoptotic pathway in renal cells. The current study revealed that Curcumin may to have potential for preventing heatstroke-induced AKI.

Curcumin alleviates acute kidney injury in a dry-heat environment by reducing oxidative stress and inflammation in a rat model.

Curcumin exhibits anti-inflammatory and antioxidant activities. We investigated the protective effects of curcumin in a renal injury rat model under dry-heat conditions. We divided Sprague-Dawley rats into four groups: dry-heat 0- (normal temperature control group), 50-, 100-, and 150-minute groups. Each group was divided into five subgroups (n = 10): normal saline (NS), sodium carboxymethylcellulose (CMCNa), and curcumin pretreated low, medium, and high-dose (50, 100, and 200 mg/kg, respectively) groups. Compared to the normal temperature group, serum creatinine, blood urea nitrogen, urinary kidney injury molecule-1, and neutrophil gelatinase-associated load changes in lipoprotein (NGAL) levels were significantly increased in the dry-heat environment group (P < .05); inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression and malondialdehyde (MDA) and related inflammatory factor levels were increased in the kidney tissue. Superoxide dismutase (SOD) and catalase (CAT) levels were decreased. However, following all curcumin pretreatment, the serum levels of kidney injury indicators and NGAL were decreased in the urine compared to those in the NS and CMCNa groups (P < .05), whereas renal SOD and CAT activities were increased and MDA was decreased (P < .05). Renal tissues of the 150-minute group showed obvious pathological changes. Compared to the NS group, pathological changes in the renal tissues of the 100- and 200-mg/kg curcumin groups were significantly reduced. Furthermore, iNOS and COX-2 expression and inflammatory factor levels were decreased after curcumin treatment. Curcumin exerted renoprotective effects that were likely mediated by its antioxidant and anti-inflammatory effects in a dry-heat environment rat model.

Media convergence of comprehensive preventive medical journals / 上海预防医学

Media convergence is the combination and convergence of every element of media in forms of breakdown of traditional classification, formats and distribution etc. It means the blending of its contents, consumers and operations in full and a new media was developed named as new media. The paper tries to explore the media convergence by starting from the paper-printed media, especially from the scientific journals. It is obvious that the basement is the electronization of media, comprehensive use of multi-technology is the fundamental tools, and it made the results of the inevitability of deep changes in term of thoughts, mindset and managerial principles as well. At the same time, the adverse effect of media convergence consequently coming from the freedom and openness of media convergence will be considered and avoided, so the surveillance of administrative functions and technicals should be adopted or developed accordingly.

Writing and editing of both contributed papers and publications in the first half year of 2020 from Shanghai Journal of Preventive Medicine / 上海预防医学

objective:To analyze the contributed papers and publications in the first half year of 2020 from Shanghai Journal of Preventive Medicine， especially the COVID-19 papers， to provide basis for the academic journals to win out during the public hot points. Methods:All the papers contributed in the first half year of 2020 from Shanghai Journal of Preventive Medicine， were collected to analyze the sources parameters， editing parameters. All published papers were collected to analyze the sources parameters， editing parameters and their usages （downloads and citations）. Results:There were 450 papers contributed in the first half year of 2020， 129 papers were accepted accounting for 28.67%. Among them， 116 papers were COVID-19 papers accounting for 25.78%， and 32 papers were accepted accounting for 24.81%. the March was the highest month of contribution， also for COVID-19 papers. Many academic domains such as infectious disease， women and children health， clinic science， chronic disease， social medicine， public hygiene and others were predominated among those papers. COVID-19 papers dominated in domains of infectious disease and social medicine. According to the non-COVID-19 papers， the COVID-19 papers had higher numbers of peer reviewers， lower days for back improvement， lower days for refusals or acceptance， also had lower copy percentages by plagiarism check （all P<0.05）. there were 106 papers published in the first half year of 2020. Published COVID-19 papers had higher number of authors， higher numbers of references in term of governments reports， foreign references and less than 5 years references （all P<0.05）. Those published COVID-19 papers had better usages than those no-COVID-19 papers， adjusted downloads were 2 077.37/year vs 111.53/year， adjusted citations were 12.99/year vs 0.49/year. It was obvious that the published COVID-19 papers had very excellent social influences and academic influences （P<0.001）. Conclusion:Publication in the first half year of 2020 from Shanghai Journal of Preventive Medicine is high-qualified and is good for the journal’s improvement in social influences and academic influences. It is important for academic journals to pay more attention to the hot points of public health accordingly.

Dual variable of drug loaded micelles in both particle and electrical charge on gastric cancer treatment.

Gastric cancer is a malignant tumour characterised by the uncontrolled cell growth. The incidence and mortality of gastric cancer remain high for the invasion and metastasis. We are urgently seeking a risk-free and effective treatment strategy for gastric cancer. In this study, paclitaxel and tetrandrine were encapsulated in the inner core of micelles, and DSPE-PEG2000-CPP and HA were modified on the micellar surface. HA/CPP modified paclitaxel plus tetrandrine micelles had a suitable particle size (90 nm) for permeating tumour tissue. The zeta potential of the targeting micelles was 8.37 mV after hydrolysis by HAase solution. Results of in vitro experiments indicated that HA/CPP modified paclitaxel plus tetrandrine micelles + HAase could enhance the intracellular uptake, inhibit the formation of neovascularization, block the process of EMT and destroy the invasion and metastasis. In vivo assays indicated that HA/CPP modified paclitaxel plus tetrandrine micelles could be selectively accumulated into tumour sites and exhibited the strong antitumor activity with negligible toxicity. These results suggested that HA/CPP modified paclitaxel plus tetrandrine micelles might provide a new strategy for treating gastric cancer.

GGP modified daunorubicin plus dioscin liposomes inhibit breast cancer by suppressing epithelial-mesenchymal transition.

Tumor invasion and metastasis are the nodus of anti-tumor. Epithelial cell-mesenchymal transition is widely regarded as one of the key steps in the invasion and metastasis of breast cancer. In this study, GGP modified daunorubicin plus dioscin liposomes are constructed and characterized. GGP modified daunorubicin plus dioscin liposome has suitable particle size, narrow PDI, zeta potential of about -5 mV, long cycle effect, and enhanced cell uptake due to surface modification of GGP making the liposome could enter the inside of the tumor to fully exert its anti-tumor effect. The results of in vitro experiments show that the liposome has superior killing effect on tumor cells and invasion. In vivo results indicate that the liposome prolongs the drug's prolonged time in the body and accumulates at the tumor site with little systemic toxicity. In short, the targeted liposome can effectively inhibit tumor invasion and may provide a new strategy for the treatment of invasive breast cancer.

RPV-modified epirubicin and dioscin co-delivery liposomes suppress non-small cell lung cancer growth by limiting nutrition supply.

Chemotherapy for non-small cell lung cancer (NSCLC) is far from satisfactory, mainly due to poor targeting of antitumor drugs and self-adaptations of the tumors. Angiogenesis, vasculogenic mimicry (VM) channels, migration, and invasion are the main ways for tumors to obtain nutrition. Herein, RPV-modified epirubicin and dioscin co-delivery liposomes were successfully prepared. These liposomes showed ideal physicochemical properties, enhanced tumor targeting and accumulation in tumor sites, and inhibited VM channel formation, tumor angiogenesis, migration and invasion. The liposomes also downregulated VM-related and angiogenesis-related proteins in vitro. Furthermore, when tested in vivo, the targeted co-delivery liposomes increased selective accumulation of drugs in tumor sites and showed extended stability in blood circulation. In conclusion, RPV-modified epirubicin and dioscin co-delivery liposomes showed strong antitumor efficacy in vivo and could thus be considered a promising strategy for NSCLC treatment.

Combination of targeted daunorubicin liposomes and targeted emodin liposomes for treatment of invasive breast cancer.

Conventional treatment fails to completely eliminate highly invasive breast cancer cells, and most surviving breast cancer cells tend to reproliferate and metastasize by forming vasculogenic mimicry (VM) channels. Thus, a type of targeted liposomes was developed by modification with arginine8-glycine-aspartic acid (R8GD) to encapsulate daunorubicin and emodin separately. A combination of the two targeted liposomes was then developed to destroy VM channels and inhibit tumour metastasis. MDA-MB-435S cells, a highly invasive breast cancer, were then evaluated in vitro and in mice. The experiments indicated that R8GD modified daunorubicin liposomes plus R8GD modified emodin liposomes had small particle size, uniform particle size distribution and high drug encapsulation rate. The combination of the two targeted liposomes exerted strong toxicity on the MDA-MB-435S cells and effectively inhibited the formation of VM channels and the metastasis of tumour cells. Action mechanism studies showed that the R8GD modified daunorubicin liposomes plus R8GD modified emodin liposomes could downregulate some metastasis-related proteins, including MMP-2, VE-cad, TGF-ß1 and HIF-1α. These studies also demonstrated that the targeted liposomes allowed the chemotherapeutic drug to selectively accumulate at tumour site, thus exhibiting a distinct antitumor effect. Therefore, the combination of targeted daunorubicin liposomes and targeted emodin liposomes can provide a potential treatment for invasive breast cancer.