Comparison of two methods for tumour-targeting peptide modification of liposomes.

Liposomes decorated with tumour-targeting cell-penetrating peptides can enhance specific drug delivery at the tumour site. The TR peptide, c(RGDfK)-AGYLLGHINLHHLAHL(Aib)HHIL, is pH-sensitive and actively targets tumour cells that overexpress integrin receptor αvß3, such as B16F10 melanoma cells. Liposomes can be modified with the TR peptide by two different methods: utilization of the cysteine residue on TR to link DSPE-PEG2000-Mal contained in the liposome formula (LIPTR) or decoration of TR with a C18 stearyl chain (C18-TR) for direct insertion into the liposomal phospholipid bilayer through electrostatic and hydrophobic interactions (LIPC18-TR). We found that both TR and C18-TR effectively reversed the surface charge of the liposomes when the systems encountered the low pH of the tumour microenvironment, but LIPC18-TR exhibited a greater increase in the charge, which led to higher cellular uptake efficiency. Correspondingly, the IC50 values of PTX-LIPTR and PTX-LIPC18-TR in B16F10 cells in vitro were 2.1-fold and 2.5-fold lower than that of the unmodified PTX-loaded liposomes (PTX-LIP), respectively, in an acidic microenvironment (pH 6.3). In B16F10 tumour-bearing mice, intravenous administration of PTX-LIPTR and PTX-LIPC18-TR (8 mg/kg PTX every other day for a total of 4 injections) caused tumour reduction ratios of 39.4% and 56.1%, respectively, compared to 20.8% after PTX-LIP administration. Thus, we demonstrated that TR peptide modification could improve the antitumour efficiency of liposomal delivery systems, with C18-TR presenting significantly better results. After investigating different modification methods, our data show that selecting an adequate method is vital even when the same molecule is used for decoration.

Changes in Lipidomics, Metabolomics, and the Gut Microbiota in CDAA-Induced NAFLD Mice after Polyene Phosphatidylcholine Treatment.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in most parts of the world. Although there is no first-line drug approved for the treatment of NAFLD, polyene phosphatidylcholine (PPC) is used by clinicians to treat NAFLD patients. This study aimed to evaluate the efficacy of PPC on a mice model of NAFLD, and to study the PPC's mechanism of action. The mice were fed a choline-deficient, L-amino acid-defined (CDAA) diet to induce NAFLD and were subsequently treated with PPC. The treatment effects were evaluated by the liver index, histopathological examination, and routine blood chemistry analyses. Lipidomics and metabolomics analyses of 54 samples were carried out using ultraperformance liquid chromatography (UPLC) coupled to a mass spectrometer to select for changes in metabolites associated with CDAA diet-induced NAFLD and the effects of PPC treatment. The intestinal flora of mice were extracted for gene sequencing to find differences before and after the induction of NAFLD and PPC treatment. PPC significantly improved the CDAA diet-induced NAFLD condition in mice. A total of 19 metabolites including 5 polar metabolites and 14 lipids showed marked changes. In addition, significant differences in the abundance of Lactobacillus were associated with NAFLD. We inferred that the protective therapeutic effect of PPC on the liver was related to the supplement of phosphatidylcholine, lysophosphatidylcholine, and sphingomyelin (PC, LPC, and SM, resectively) and acylcarnitine metabolism. This study developed a methodology for exploring the pathogenesis of NAFLD and can be extended to other therapeutic agents for treating NAFLD.

Lipidomic-based investigation into the therapeutic effects of polyene phosphatidylcholine and Babao Dan on rats with non-alcoholic fatty liver disease.

In recent years, with the improvement of people's living standards, non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in the world. In this paper, the metabolic disorders in Sprague Dawley (SD) rats were induced by a choline-deficient, l-amino acid-defined (CDAA) diet. The therapeutic effects of polyene phosphatidylcholine (PPC) and Babao Dan (BBD) on NAFLD were observed. Lipidomic analysis was performed using ultra-high-performance liquid chromatography-Orbitrap MS, and data analysis and lipid identification were performed using the software LipidSearch. Both PPC and BBD can reduce lipid accumulation in the liver and improve abnormal biochemical indicators in rats, including reduction of triglycerides, total cholesterol, alanine transaminase and aspartate transaminase in serum. In addition, lipids in rat serum were systematically analyzed by lipidomics. The lipidomic results showed that the most obvious lipids with abnormal metabolism in CDAA diet-induced rats were glycerides (triglycerides and diacylglycerols), phospholipids and cholesterol esters. Both BBD and PPC partly reversed the disturbance to lipids induced by the CDAA diet. PPC may be more effective than BBD in alleviating NAFLD because it has a better effect on inhibiting the abnormal accumulation of lipids and reducing the inflammatory reaction in the body.

Characterization of the WAK Gene Family Reveals Genes for FHB Resistance in Bread Wheat (Triticum aestivum L.).

Wall-associated kinases (WAKs) are important receptor-like proteins that play major roles in plant defense against pathogens. Fusarium head blight (FHB), one of the most widespread and devastating crop diseases, reduces wheat yield and leads to quality deterioration. Although WAK gene families have been studied in many plants, systematic research on bread wheat (Triticum aestivum) and its role in FHB resistance, in particular, is lacking. In this study, we identified and characterized 320 genes of the TaWAK family in wheat distributed across all chromosomes except 4B and divided them into three phylogenetic groups. Duplication and synteny analyses provided valuable information on the evolutionary characteristics of the TaWAK genes. The gene expression pattern analysis suggested that TaWAK genes play diverse roles in plant biological processes and that at least 30 genes may be involved in the response to Fusarium infection in wheat spikes, with most of the genes contributing to pectin- and chitin-induced defense pathways. Furthermore, 45 TaWAK genes were identified within 17 hcmQTLs that are related to wheat FHB resistance. Our findings provide potential candidate genes for improving FHB resistance and insights into the future functional analysis of TaWAK genes in wheat.

Unmixing the coupling influence from driving factors on vegetation changes considering spatio-temporal heterogeneity in mining areas: a case study in Xilinhot, Inner Mongolia, China.

Considering the spatio-temporal heterogeneity, this study resolved the coupling influence of a variety of driving factors on vegetation changes in mining areas and discovered the influencing characteristics of the respective driving factors, especially mining activities. First, the spatio-temporal characteristics of FVC (fractional vegetation cover) variation were analyzed in the Sheng-Li mining area. Second, the quantitative relationships among the natural factors (temperature, precipitation, and elevation), artificial factors (mining activities, urban activities), and FVC were constructed by GTWR (geographically and temporally weighted regression) to quantify the contribution of each factor to the change in FVC. Third, the influencing characteristics of the respective driving factors, especially mining activities, were analyzed and summarized. The results show that (1) the FVC change was mainly influenced by natural factors in the areas far from mines and towns and artificial factors in the areas close to mines and towns. (2) The contribution of mining activities to vegetation change (C-Mine) was spatially characterized by two features: (a) distance attenuation characteristics: C-Mine showed logarithmic decrement with distance; (b) directional heterogeneity: C-Mine varied significantly in different directions. In particular, there was a high C-Mine area located near multiple mining areas, and the range of this area shifted to include the mine with more production over time. Overall, unmixing the coupling influence from driving factors with spatio-temporal heterogeneity and achieving a quantitative description of the influencing characteristics in mining areas were the main contributions of this study. The quantification methods and results in this paper provide important support for decision-making on ecological protection and restoration in mining areas.

The Influence of Online STEM Education Camps on Students' Self-Efficacy, Computational Thinking, and Task Value.

As a result of COVID-19, various forms of education and teaching are moving online. However, the notion of an online STEM camp is still in its beginnings, and there is little relevant research and experience in this context. At the beginning of April 2021, the research team launched an online STEM charity camp with the theme of "Shen Nong Tastes Herbs." Participants included 113 third- and fourth-grade primary school students ranging from 8 to 12 years of age from four schools in Karamay, Xinjiang Uygur Autonomous Region with weak educational capabilities. The camp lasted for 3 days and included 7 activities, while remote teaching was accomplished through Dingtalk. Pre- and post-test questionnaires and interviews were used to explore the impact of this camp on students. We found that online STEM camps could improve students' self-efficacy, computational thinking, and task value, and there is a significant improvement in the self-efficacy (p = 0.000) and task value (p = 0.001) dimensions. In addition, students with high self-efficacy had higher scores in the other two dimensions. Finally, we summarized the experiences and gains of students and teachers and proposed suggestions for developing online camps based on this experience. [Table: see text]. Supplementary Information: The online version contains supplementary material available at 10.1007/s10956-022-09967-y.

Simple and Rapid Functionalization of Gold Nanorods with Oligonucleotides Using an mPEG-SH/Tween 20-Assisted Approach.

DNA conjugated gold nanorods (AuNRs) are widely applied for nanostructure assembly, gene therapy, biosensing, and drug delivery. However, it is still a great challenge to attach thiolated DNA on AuNRs, because the positively charged AuNRs readily aggregate in the presence of negatively charged DNA. This article reports an mPEG-SH/Tween 20-assisted method to load thiolated DNA on AuNRs in 1 h. Tween 20 and mPEG-SH are used to synergistically displace CTAB on the surface of AuNRs by repeated centrifugation and resuspension, and thiolated DNA are attached to AuNRs in the presence of 1 M NaCl, 100 mM MgCl2, or 100 mM citrate. AuNRs with different sizes and aspect ratios can be functionalized with DNA by this method. The number of DNA loaded on each AuNR can be easily controlled by the concentrations of mPEG-SH and Tween 20 or the ratio between DNA and AuNR. Functionalized AuNRs were used for nanoparticle assembly and cancer cell imaging to confirm that DNA anchored on the surface of AuNRs retains its hybridization and molecular recognition capability. The new method is easy, rapid, and robust for the preparation of DNA functionalized AuNRs for a variety of applications such as cancer therapy, drug delivery, self-assembly, and imaging.

Automated generation of consistent annual maximum NDVI on coal bases with a new algorithm.

Coal is one of the most important fossil energy sources and is ensuring global energy security. Annual maximum NDVI (Normalized Difference Vegetation Index) data is an important indicator for the research in balancing coal mining and vegetation conservation. However, the existing annual maximum NDVI data displayed lower values with temporally inconsistent and a noticeable mosaic line. Here we propose an algorithm for automatically generating the annual maximum NDVI of China's coal bases in Google Earth Engine called: Auto-NDVIcb. The accuracy of the Auto-NDVIcb algorithm has been verified with an average RMSE of 0.087 for the 14 coal bases from 2013 to 2022. Based on the proposed Auto-NDVIcb algorithm, an annual maximum NDVI dataset for all 14 coal bases in China from 2013 to 2022 was publicly released. This dataset can be fast and automatically updated online. Hence, the public dataset will continuously serve to monitor the vegetation change induced by coal mining, exploring the mechanism of vegetation degradation, and providing scientific data for developing vegetation protection policies in coal mines.

Circulating cytokines and vascular dementia: A bi-directional Mendelian randomization study.

Inflammatory responses are associated with the development of vascular dementia (VaD). Circulating cytokines modulate the inflammatory response and are important for the immune system. To further elucidate the role of the immune system in VaD, we used Mendelian randomization (MR) to comprehensively and bi-directionally assess the role of circulating cytokines in VaD. Using state-of-the-art genome-wide association studies, we primarily assessed whether different genetic levels of 41 circulating cytokines affect the risk of developing VaD and, in turn, whether the genetic risk of VaD affects these circulating cytokines. We used inverse variance weighting (IVW) and several other MR methods to assess the bidirectional causality between circulating cytokines and VaD, and performed sensitivity analyses. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) was inversely associated with VaD risk [odds ratio (OR): 0.74, 95 % confidence interval (CI): 0.60-0.92, P = 0.007, 0.007]. VaD was associated with seven circulating cytokines: macrophage inflammatory protein 1b (MIP-1 beta) [OR: 1.05, 95 % CI: 1.01-1.08, P = 0.009], Interleukin-12p70 (IL-12) [OR: 1.04, 95 % CI: 1.00-1.08, P = 0.047], Interleukin-17 (IL-17) [OR: 1.04, 95 % CI: 1.00-1.07, P = 0.038], Interleukin-7 (IL-7) [OR: 1.07, 95 % CI: 1.02-1.12, P = 0.009], Interferon gamma (IFN-γ) [OR: 1.03, 95 % CI: 1.00-1.07, P = 0.046], Granulocyte-colony stimulating factor (GCSF) [OR: 1.06, 95 % CI: 1.02-1.09, P = 0.001], Fibroblast growth factor (FGF) [P = 0.001], and Fibroblast growth factor (FGF) [P = 0.001]. Fibroblast growth factor basic (FGF-Basic) [OR: 1.04, 95 % CI: 1.01-1.08, P = 0.02] were positively correlated. Circulating cytokines are associated with VaD, and further studies are needed to determine whether they are effective targets for intervention to prevent or treat VaD.

Replacing cholesterol with asiatic acid to prolong circulation and enhance anti-metastatic effects of non-PEGylated liposomes.

Cholesterol is an indispensable component of most liposomes, heavily influencing their physical and surface properties. In this study, cholesterol in non-PEGylated liposomes was replaced by its analog, asiatic acid (AA), to generate liposomes with an alternative composition. These AA liposomes are generally smaller and more rigid than conventional liposomes, circulate longer in the body, and accumulate more in primary tumors and lung metastases in vivo. On the other hand, as an active ingredient, AA can decrease TGF-ß secretion to inhibit the epithelial-mesenchymal transition (EMT) process, increase the sensitivity of tumor cells to doxorubicin (DOX), and synergize with DOX to enhance the immune response, thus improving their antitumor and anti-metastasis efficiency. Based on this rationale, DOX-loaded AA liposomes were fabricated and tested against triple-negative breast cancer (TNBC). Results showed that compared with conventional liposomes, the DOX-AALip provided approximately 28.4% higher tumor volume reduction with almost no metastatic nodules in the mouse model. Our data demonstrate that AA liposomes are safe, simple, and efficient, and thus in many situations may be used instead of conventional liposomes, having good potential for further clinical translational development.

Construction and validation of a cuproptosis-related five-lncRNA signature for predicting prognosis, immune response and drug sensitivity in breast cancer.

BACKGROUND: Despite advances in treatment, recurrence and mortality rates from breast cancer (BrCa) continue to rise, clinical effectiveness is limited, and prognosis remains disappointing, especially for patients with HER2-positive, triple-negative, or advanced breast cancer. Based on cuproptosis-related long noncoding RNAs (CRLs), this study aims to create a predictive signature to assess the prognosis in patients with BrCa. METHODS: The related CRLs RNA-seq data clinicopathological data were collected from The Cancer Genome Atlas (TCGA) database, and the predictive model was constructed after correlation analysis. Subsequently, we examined and validated connections and changes in the CRLs model with prognostic features (including risk curves, ROC curves and nomograms), pathway and functional enrichment, tumor mutation (TMB), tumor immune dysfunction and exclusion (TIDE) and treatment sensitivity. RESULTS: A prediction model formula composed of 5 CRLs was obtained, and divided breast cancer patients into high and low risk subgroups according to the obtained risk scores. The results showed that the overall survival (OS) of patients in the high-risk group was lower than that in the low-risk group, and the AUC of all samples at 1, 3 and 5 years were 0.704, 0.668 and 0.647, respectively. It was indicated that CRLs prognostic model could independently predict prognostic indicators of BrCa patients. In addition, analysis of gene set enrichment, immune function, TMB, and TIDE showed that these differentially expressed CRLs had a wealth of related pathways and functions, and might be closely related to immune response and immune microenvironment. Additionally, TP53 was found to have the highest mutation frequency in high-risk group (40%), while PIK3CA was found to have the highest mutation frequency in low-risk group (42%), which might become new targets for targeted therapy. Finally, we compared susceptibility to anticancer agents to identify potential treatment options for breast cancer. Lapatinib, Sunitinib, Phenformin, Idelalisib, Ruxolitinib, Cabozantinib were more sensitive to patients in the low-risk group, while Sorafenib, Vinorelbine, Pyrimethamine were more sensitive to patients in high-risk group, namely, these drugs could potentially be used in the future to treat breast cancer patients grouped according to the risk model. CONCLUSION: This study identified CRLs associated with breast cancer and provided a tailored tool for predicting prognosis, immune response, and drug sensitivity in patients with BrCa.

Moxibustion Treatment of COVID-19 and Rehabilitation Period of COVID-19: A Scoping Review.

Objective: The aim of this study is to provide a scoping review of the clinical literature on moxibustion therapy for the treatment of Coronavirus disease 2019 (COVID-19). Design: The PubMed, Embase, Cochrane Library, MEDLINE, CNKI, Wanfang, and VIP databases were searched from January 1, 2020, to August 31, 2022. Essential data were extracted from each article, and the data were displayed using tables and graphs. The study did not require IRB approval. Results: This scoping review included 14 research articles: 8 observational studies, 5 randomized controlled trials, and 1 nonrandomized clinical trial. All the studies were published by Chinese scholars. The findings revealed that moxibustion can contribute to reducing the symptoms of patients with COVID-19, improving inflammation and immune indicators, and shortening the time of nucleic acid negative conversion. Moxibustion confers curative effects on patients of all ages and degrees of illness. In addition, moxibustion can optimize the prognosis of patients in the rehabilitation period. The most commonly chosen acupoints are ST36, RN4, RN8, and RN12. No side effect was mentioned in the included studies. Conclusion: Moxibustion can produce a good effect in the treatment and rehabilitation of patients with COVID-19. It is safe, effective, simple, and noninvasive and should be included as standard care.

Lipid accumulation product is a better predictor of metabolic syndrome in Chinese adolescents: a cross-sectional study.

Aim: Confirm and compare the degree of associations of non-traditional lipid profiles and metabolic syndrome (MetS) in Chinese adolescents, determine the lipid parameter with better predictive potential, and investigate their discriminatory power on MetS. Methods: Medical measurements, including anthropometric measurements and biochemical blood tests, were undergone among a total sample of 1112 adolescents (564 boys and 548 girls) aged from 13 to 18 years. Univariate and multivariate logistic regression analyses were applied for assessing the relationships between the levels of traditional/non-traditional lipid profiles and MetS. We performed Receiver Operating Characteristic (ROC) analyses to mensurate the effectiveness of lipid accumulation product (LAP) on the diagnosis of MetS. Meanwhile, areas under the ROC curve and the cut-off values were calculated for MetS and its components. Results: Univariate analysis showed that all our lipid profiles were closely associated with MetS (P< 0.05). LAP index showed the closest association with MetS than the other lipid profiles. Additionally, ROC analyses indicated that the LAP index showed sufficient capabilities to identify adolescents with MetS and its components. Conclusion: The LAP index is a simple and efficient tool to identify individuals with MetS in Chinese adolescents.

Superimposed OER and UOR performances by the interaction of each component in an Fe-Mn electrocatalyst.

The oxygen evolution reaction (OER) and alternative urea oxidation reaction (UOR) are both important half reactions correlated with hydrogen production. Transition metal based catalysts with double metal composition exhibit excellent electrocatalytic performance for the OER or UOR due to their synergetic effect and coupling of different active sites. However, the development of OER/UOR bifunctional electrocatalysts is unsatisfying and the role of each metallic active site in the OER and UOR is still unclear. Herein, we report a Fe-Mn based OER and UOR bifunctional catalyst through a simple one-step electrodeposition method. For the OER, the introduction of Mn improves the conductivity of the catalysts and fine-tunes the electron density of the Fe active sites. For the UOR, both Fe and Mn act as active sites and their coupling effect further improves the UOR activity. The catalyst with the optimal Mn/Fe ratio achieved an overpotential of 237 mV for the OER and a potential of 1.35 V for the UOR at 100 mA cm-2. This study provides a simple synthesis protocol for constructing bifunctional catalysts for green hydrogen production.

Suppression of methane uptake by precipitation pulses and long-term nitrogen addition in a semi-arid meadow steppe in northeast China.

In the context of global change, the frequency of precipitation pulses is expected to decrease while nitrogen (N) addition is expected to increase, which will have a crucial effect on soil C cycling processes as well as methane (CH4) fluxes. The interactive effects of precipitation pulses and N addition on ecosystem CH4 fluxes, however, remain largely unknown in grassland. In this study, a series of precipitation pulses (0, 5, 10, 20, and 50 mm) and long-term N addition (0 and 10 g N m-2 yr-1, 10 years) was simulated to investigate their effects on CH4 fluxes in a semi-arid grassland. The results showed that large precipitation pulses (10 mm, 20 mm, and 50 mm) had a negative pulsing effect on CH4 fluxes and relatively decreased the peak CH4 fluxes by 203-362% compared with 0 mm precipitation pulse. The large precipitation pulses significantly inhibited CH4 absorption and decreased the cumulative CH4 fluxes by 68-88%, but small precipitation pulses (5 mm) did not significantly alter it. For the first time, we found that precipitation pulse size increased cumulative CH4 fluxes quadratically in both control and N addition treatments. The increased soil moisture caused by precipitation pulses inhibited CH4 absorption by suppressing CH4 uptake and promoting CH4 release. Nitrogen addition significantly decreased the absorption of CH4 by increasing NH4 +-N content and NO3 --N content and increased the production of CH4 by increasing aboveground biomass, ultimately suppressing CH4 uptake. Surprisingly, precipitation pulses and N addition did not interact to affect CH4 uptake because precipitation pulses and N addition had an offset effect on pH and affected CH4 fluxes through different pathways. In summary, precipitation pulses and N addition were able to suppress the absorption of CH4 from the atmosphere by soil, reducing the CH4 sink capacity of grassland ecosystems.

Florfenicol/Chlortetracycline Effect on Pharmacodynamic Indices for Mutant Selection of Riemerella anatipestifer in Ducks.

Riemerella anatipestifer can cause septicemia and death in ducks and geese, leading to significant economic losses to animal farms. The emergence of resistance of R. anatipestifer to commonly used antibiotics increases the difficulty of treating R. anatipestifer infection. The aim of this study was to evaluate the utility of antibiotic combination to restrict mutant selection of multidrug-resistant (MDR) R. anatipestifer isolates. Pharmacokinetics of florfenicol and chlortetracycline in Pekin ducks were evaluated using both noncompartmental analysis and population pharmacokinetic models. The areas under the curve of florfenicol and chlortetracycline after single 20 and 10 mg/kg oral administration were 49.3 and 6.84 mg*h/L, respectively. Chlortetracycline exhibited high apparent clearance and low systemic exposure. Minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) values of the two antibiotics were determined in 10 and 2 MDR R. anatipestifer isolates, respectively, to derive fTMSW (the fraction of time over 24 hours wherein the free drug concentration was within the mutant selection window [MSW]) and fT>MPC (the fraction of time that the free drug concentration was above the MPC). Both fTMSW and fT>MPC were estimated from simulated concentration-time profiles relative to MIC and MPC. Florfenicol and chlortetracycline combination have additive activities against R. anatipestifer in majority of isolates and could significantly decrease monotherapy MPC of florfenicol and chlortetracycline, as well as optimize both fTMSW and fT>MPC parameters, provided that the bioavailability of chlortetracycline is improved. The application of pharmacokinetic/pharmacodynamic analyses to MPC concepts to restrict selection of mutant bacterial strains can help improve short- and long-term outcomes of antibiotic treatment in animal farms.

Multifunctional Size-Expandable Nanomedicines Enhance Tumor Accumulation and Penetration for Synergistic Chemo-Photothermal Therapy.

Size expansion can effectively improve tumor accumulation of nanocarriers where precise control is required. A dual-responsive nanocarrier stimulated by both endogenous pH and exogenous heat stimuli can change its size. Herein, a nanoparticle composed of poly(N,N-diethyl acrylamide) (PDEAA) and poly(2-(diisopropylamino) ethyl methacrylate) (PDPA) is developed. The antitumor drug celastrol (CLT) and the photosensitizer indocyanine green (ICG) are then loaded in it to form CIPP. ICG generates heat under near-infrared (NIR) stimulation to kill tumor cells and enhance CIPP penetration. Meanwhile, CIPP expands in response to hyperthermia and acid tumor microenvironments, preventing itself from returning to the blood flow, thus accumulating in tumor sites. Ultimately, the acidic lysosomal environment in tumor cells disintegrates CIPP to release CLT, directly inducing immunogenic cell death and sensitizing tumor cells for hyperthermia by disrupting the interaction of heat shock protein 90 and P50cdc37. Most of the tumors in B16F10-bearing mice are eradicated after single laser irradiation. The dual-responsive CIPP with multiple functions and simple design displays a synergistic antitumor effect. This study provides a basis for developing size-expandable stimulus-responsive drug delivery systems against tumors.

Enhanced anti-metastatic therapy with down-regulation of heparinase expression by ROS-responsive micellar nanoparticles.

Metastasis is a major sign of malignant tumors which plays a vital role in cancer-related death. Suppressing metastasis is an important way to improve the survival rate of cancer patients. Herein, multifunctional PEG-LAM-PPS nanoparticles (nPLPs) are fabricated as both nanocarriers and anti-metastatic agents for tumor treatment. In this system, laminarin sulfate (LAM) suppresses metastasis by reducing heparinase and protecting the extracellular matrix; the ROS-sensitive polypropylene sulfide (PPS) improves the release of the loaded drug in the tumor microenvironment. This is the first time that laminarin sulfate has been used as a carrier to inhibit the expression of heparinase and treat melanoma lung metastasis. The blank nanoparticles are excellently safe and showed high anti-metastatic efficacy in melanoma lung metastatic mouse models, reducing metastatic nodules by 60%. They significantly improved the anti-tumor efficacy of the loaded drug doxorubicin, provided ∼33% further reduction of the tumor volume and 50% further reduction of the metastatic nodule number compared with free doxorubicin. Thus, these simple and versatile micellar nanoparticles composed of biocompatible materials offer a promising vehicle for treating invasive solid tumors and metastases.

Improved melanoma suppression with target-delivered TRAIL and Paclitaxel by a multifunctional nanocarrier.

Malignant melanoma, a highly dangerous type of skin cancer, is usually resistant to pro-apoptosis agents such as tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) due to low death receptor expression levels. After verifying combination of chemotherapy drug paclitaxel (PTX) and TRAIL could significantly enhance their anti-melanoma effects, we developed a liposomal melanoma target-delivery system with tumor microenvironment responsiveness (TRAIL-[Lip-PTX]C18-TR) to co-deliver TRAIL and PTX. TRAIL is attached to negatively-charged liposome surface while PTX is encapsulated inside, with final surface modification of a stearyl chain (C18) fused pH-sensitive cell-penetrating peptide (TR). Here, C18-TR could specifically binds to melanoma-rich integrin receptors αvß3 for melanoma targeting, help release TRAIL in low pH microenvironment by reversing the liposomal charge, and facilitate consequent liposome internalization. TRAIL-[Lip-PTX]C18-TR displayed significantly better in vitro half-maximal inhibitory concentration (IC50) than other formulations, and an in vivo tumor inhibition rate of 93.8%. Mechanistic study revealed that this synergistic effect is associated with the upregulation of death receptors DR4/5 by PTX. This co-delivery system significantly improved TRAIL-based therapy against melanoma, and provided a simple platform to co-deliver other drugs/agents for melanoma treatment.

Treatment of atherosclerotic plaque: perspectives on theranostics.

OBJECTIVES: Atherosclerosis, a progressive condition characterised by the build-up of plaque due to the accumulation of low-density lipoprotein and fibrous substances in the damaged arteries, is the major underlying pathology of most cardiovascular diseases. Despite the evidence of the efficacy of the present treatments for atherosclerosis, the complex and poorly understood underlying mechanisms of atherosclerosis development and progression have prevented them from reaching their full potential. Novel alternative treatments like usage of nanomedicines and theranostics are gaining attention of the researchers worldwide. This review will briefly discuss the current medications for the disease and explore potential future developments based on theranostics nanomaterials that may help resolve atherosclerotic cardiovascular disease. KEY FINDINGS: Various drugs can slow the effects of atherosclerosis. They include hyperlipidaemia medications, anti-platelet drugs, hypertension and hyperglycaemia medications. Most of the theranostic agents developed for atherosclerosis have shown the feasibility of rapid and noninvasive diagnosis, as well as effective and specific treatment in animal models. However, there are still some limitation exist in their structure design, stability, targeting efficacy, toxicity and production, which should be optimized in order to develop clinically acceptable nanoparticle based theronostics for atherosclerosis. SUMMARY: Current medications for atherosclerosis and potential theranostic nanomaterials developed for the disease are discussed in the current review. Further investigations remain to be carried out to achieve clinical translation of theranostic agents for atherosclerosis.