Aptamer-Modified Nb2C Multifunctional Nanomedicine for Targeted Photothermal/Chemotherapy Combined Therapy of Tumor.

The poor delivery efficiency of nanotherapeutic drugs and their potential off-target toxicity significantly limit their effectiveness and extensive application. An active targeting system with high efficiency and few side effects is a promising strategy for tumor therapy. Herein, a multifunctional nanomedicine Nb2C-PAA-DOX@Apt-M (NDA-M) was constructed for targeted photothermal/chemotherapy (PTT/CHT) combined tumor therapy. The specific targeting ability of aptamer could effectively enhance the absorption of nanomedicine by the MCF-7 cell. By employing Apt-M, the NDA-M nanosheets demonstrated targeted delivery to MCF-7 cells, resulting in enhanced intracellular drug concentration. Under 1060 nm laser irradiation, a rapid temperature increase of the NDA-M was observed within the tumor region to achieve PTT. Meanwhile, CHT was triggered when DOX release was induced by photothermal/acid stimulation. The experimental results demonstrated that aptamer-mediated targeting achieved enhanced PTT/CHT efficacy both in vitro and in vivo. Notably, NDA-M induced complete ablation of solid tumors without any adverse side effects in mice. This study demonstrated new and promising tactics for the development of nanomaterials for targeted tumor therapy.

A sandwich FRET biosensor for lysozyme detection based on peptide-functionalized gold nanoparticles and FAM-labeled aptamer.

Lysozyme (LYZ) plays a crucial role in the body's immune defense system. Monitoring LYZ levels can provide valuable insights into the diagnosis and severity assessment of various diseases. Traditionally, antibody-based sandwich assays are employed for LYZ detection, but they are often time-consuming and operationally complicated. In this research, a novel sandwich FRET biosensor was developed, which enables rapid detection of LYZ based on peptide-functionalized gold nanoparticles (pAuNPs) and FAM-labeled aptamer (Apt-FAM). Initially, a mixture of Apt-FAM and pAuNPs resulted in partial quenching of the Apt-FAM fluorescence emission through an inner filter effect (IFE), with negligible energy transfer because of the electrostatic repulsion between the negatively charged pAuNPs and Apt-FAM. The introduction of LYZ into the mixture drove the specific binding of Apt-FAM and pAuNPs to LYZ, facilitating the formation of a pAuNPs-LYZ-aptamer sandwich structure. The formation of this complex drew the pAuNPs and Apt-FAM into close enough proximity to enable FRET to occur, which in turn effectively quenched the fluorescence emission of FAM. The decrease in FAM fluorescence intensity was correlated with the increasing concentration of LYZ. Thus, a sandwich FRET biosensor was successfully developed for LYZ detection with a linear detection range of 0-1.75 µM and a detection limit of 85 nM. Additionally, the biosensor allowed visual detection of LYZ in a 96-well microplate, with a rapid response time of just 15 s. This study introduces a innovative sandwich FRET biosensor that combines aptamer and peptide recognition elements, offering a fast and antibody-free method for protein detection.

Glycogen-binding protein STBD1: Molecule and role in pathophysiology.

Starch-binding domain-containing protein 1 (STBD1) is a glycogen-binding protein discovered in skeletal muscle gene differential expression that is pivotal to cellular energy metabolism. Recent studies have indicated that STBD1 is involved in many physiological processes, such as glycophagy, glycogen accumulation, and lipid droplet formation. Moreover, dysregulation of STBD1 causes multiple diseases, including cardiovascular disease, metabolic disease, and even cancer. Deletions and/or mutations in STBD1 promote tumorigenesis. Therefore, STBD1 has garnered considerable interest in the pathology community. In this review, we first summarized the current understanding of STBD1, including its structure, subcellular localization, tissue distribution, and biological functions. Next, we examined the roles and molecular mechanisms of STBD1 in related diseases. Based on available research, we discussed the novel function and future of STBD1, including its potential application as a therapeutic target in glycogen-related diseases. Given the significance of STBD1 in energy metabolism, an in-depth understanding of the protein is crucial for understanding physiological processes and developing therapeutic strategies for related diseases.

A new perspective on the autophagic and non-autophagic functions of the GABARAP protein family: a potential therapeutic target for human diseases.

Mammalian autophagy-related protein Atg8, including the LC3 subfamily and GABARAP subfamily. Atg8 proteins play a vital role in autophagy initiation, autophagosome formation and transport, and autophagy-lysosome fusion. GABARAP subfamily proteins (GABARAPs) share a high degree of homology with LC3 family proteins, and their unique roles are often overlooked. GABARAPs are as indispensable as LC3 in autophagy. Deletion of GABARAPs fails autophagy flux induction and autophagy lysosomal fusion, which leads to the failure of autophagy. GABARAPs are also involved in the transport of selective autophagy receptors. They are engaged in various particular autophagy processes, including mitochondrial autophagy, endoplasmic reticulum autophagy, Golgi autophagy, centrosome autophagy, and dorphagy. Furthermore, GABARAPs are closely related to the transport and delivery of the inhibitory neurotransmitter γ-GABAA and the angiotensin II AT1 receptor (AT1R), tumor growth, metastasis, and prognosis. GABARAPs also have been confirmed to be involved in various diseases, such as cancer, cardiovascular disease, and neurodegenerative diseases. In order to better understand the role and therapeutic potential of GABARAPs, this article comprehensively reviews the autophagic and non-autophagic functions of GABARAPs, as well as the research progress of the role and mechanism of GABARAPs in cancer, cardiovascular diseases and neurodegenerative diseases. It emphasizes the significance of GABARAPs in the clinical prevention and treatment of diseases, and may provide new therapeutic ideas and targets for human diseases. GABARAP and GABARAPL1 in the serum of cancer patients are positively correlated with the prognosis of patients, which can be used as a clinical biomarker, predictor and potential therapeutic target. GABARAP family proteins: autophagy and non-autophagy related functions in diseases. By Figdraw ( https://www.figdraw.com ).

Elabela-apelin-12, 17, 36/APJ system promotes platelet aggregation and thrombosis via activating the PANX1-P2X7 signaling pathway.

The elabela-apelin/angiotensin domain type 1 receptor-associated protein (APJ) system is an important regulator in certain thrombosis-related diseases such as atherosclerosis, myocardial infarction, and cerebral infarction. Our previous reports have revealed that apelin exacerbates atherosclerotic lesions. However, the relationship between the elabela-apelin/APJ system and platelet aggregation and atherothrombosis is unclear. The results of the present study demonstrate that elabela and other endogenous ligands such as apelin-12, -17, and -36 induce platelet aggregation and thrombosis by activating the pannexin1(PANX1)-P2X7 signaling pathway. Interestingly, the diuretic, spironolactone, a novel PANX1 inhibitor, alleviated elabela- and apelin isoforms-induced platelet aggregation and thrombosis. Significantly, two potential antithrombotic drugs were screened out by targeting APJ receptors, including the anti-HIV ancillary drug cobicistat and the traditional Chinese medicine monomer Schisandrin A. Both cobicistat and Schisandrin A abolished the effects of elabela and apelin isoforms on platelet aggregation, thrombosis, and cerebral infarction. In addition, cobicistat significantly attenuated thrombosis in a ponatinib-induced zebrafish trunk model. Overall, the elabela-apelin/APJ axis mediated platelet aggregation and thrombosis via the PANX1-P2X7 signaling pathway in vitro and in vivo. Blocking the APJ receptor with cobicistat/Schisandrin A or inhibiting PANX1 with spironolactone may provide novel therapeutic strategies against thrombosis.

Multifaceted functions of RPS27a: An unconventional ribosomal protein.

The ribosomal protein S27a (RPS27a) is cleaved from the fusion protein ubiquitin-RPS27a (Ub-RPS27a). Generally, Ub and RPS27a are coexpressed as a fusion protein but function independently after Ub is cleaved from RPS27a by a deubiquitinating enzyme. As an RP, RPS27a assembles into ribosomes, but it also functions independently of ribosomes. RPS27a is involved in the development and poor prognosis of various cancers, such as colorectal cancer, liver cancer, chronic myeloid leukemia, and renal carcinoma, and is associated with poor prognosis. Notably, the murine double minute 2/P53 axis is a major pathway through which RPS27a regulates cancer development. Moreover, RPS27a maintains sperm motility, regulates winged aphid indirect flight muscle degeneration, and facilitates plant growth. Additionally, RPS27a is a metalloprotein and mercury (Hg) biomarker. In the present review, we described the origin, structure, and biological functions of RPS27a.

The protective immunity induced by intranasally inoculated serotype 63 chimpanzee adenovirus vector expressing human respiratory syncytial virus prefusion fusion glycoprotein in BALB/c mice.

Human respiratory syncytial virus (RSV) is a ubiquitous pediatric pathogen causing serious lower respiratory tract disease worldwide. No licensed vaccine is currently available. In this work, the coding gene for mDS-Dav1, the full-length and prefusion conformation RSV fusion glycoprotein (F), was designed by introducing the stabilized prefusion F (preF) mutations from DS-Cav1 into the encoding gene of wild-type RSV (wtRSV) F protein. The recombinant adenovirus encoding mDS-Cav1, rChAd63-mDS-Cav1, was constructed based on serotype 63 chimpanzee adenovirus vector and characterized in vitro. After immunizing mice via intranasal route, the rChAd63-mDS-Cav1 induced enhanced neutralizing antibody and F-specific CD8+ T cell responses as well as good immune protection against RSV challenge with the absence of enhanced RSV disease (ERD) in BALB/c mice. The results indicate that rChAd63-mDS-Cav1 is a promising mucosal vaccine candidate against RSV infection and warrants further development.

Apelin/APJ signaling activates autophagy to promote human lung adenocarcinoma cell migration.

AIMS: Beclin1(BECN1) is known as an autophagy-related protein and the expression is promoted by apelin in lung adenocarcinoma cells, suggesting that apelin activates autophagy in lung adenocarcinoma. However, the functions of apelin-induced autophagy in lung adenocarcinoma tumorigenesis and deterioration are still unknown. Thus, this study aims to investigate the effects of apelin-induced autophagy on lung adenocarcinoma tumorigenesis and deterioration. MAIN METHODS: Protein expression of exogenous genes were detected by Western blotting analysis. Lung adenocarcinoma cell migration was assessed with cell migration assays. Autophagy was measured with quantification of GFP-LC3 or RFP-GFP-LC3 puncta using fluorescence microscopy in cells by an observed blinded to experimental condition and by western blot analysis of LC3 and p62 in cell lysates as well as autophagy flux. Immunofluorescence staining was performed in human lung adenocarcinoma A549 cells with p-cofilin antibody. The proteins expression in cancer specimens were examined with immunohistochemistry. KEY FINDINGS: Here, we reveal that apelin induces autophagy activation in lung adenocarcinoma. Apelin/APJ regulates BECN1 transcription via HIF1A. Apelin/APJ-activated autophagy promotes lung adenocarcinoma cell migration. Moreover, treatment with autophagy inhibitors significantly decreases apelin/APJ-induced lung adenocarcinoma cell migration. Evaluation of patient samples of lung adenocarcinoma reveals an association between APJ with BECN1 expression and a poor prognosis. SIGNIFICANCE: Our studies demonstrate that apelin-induced autophagy promotes lung adenocarcinoma cell migration which suggests a potential therapeutic target for lung adenocarcinoma.

Warburg effect is involved in apelin-13-induced human aortic vascular smooth muscle cells proliferation.

Apelin is the endogenous ligand for the G protein-coupled receptor APJ. Both apelin and APJ receptor are distributed in vascular smooth muscle cells (VSMCs) and play important roles in the cardiovascular system. Our previous reports have indicated that apelin-13 promoted the proliferation of VSMCs, but its exact mechanism remains to be further explored. The results of the present study demonstrated that the Warburg effect plays a pivotal role in apelin-13-induced human aortic vascular smooth muscle cells (HA-VSMCs) proliferation. Apelin-13 promoted the expression of glucose transporter type 1 (GLUT1), pyruvate kinase 2 (PKM2), lactate dehydrogenase A (LDHA), monocarboxylate transporter 1 (MCT1), and monocarboxylate transporter 4 (MCT4) in a dose- and time-dependent manner. Moreover, apelin-13 increased the extracellular, intracellular lactate level, and decreased adenosine triphosphate level in HA-VSMCs. Furthermore, siRNA-PKM2 reversed extracellular and intracellular lactate generation and inhibited the proliferation of HA-VSMCs induced by apelin-13. Downregulation of LDHA also significantly prevented extracellular and intracellular lactate generation and inhibited the proliferation of HA-VSMCs induced by apelin-13. Taken together, our results demonstrated a novel mechanism for HA-VSMCs proliferation induced by apelin-13 via Warburg effect.

Ferritinophagy activation and sideroflexin1-dependent mitochondria iron overload is involved in apelin-13-induced cardiomyocytes hypertrophy.

Excess iron accumulation and cardiac oxidative stress have been shown as important mediators of cardiac hypertrophy, whereas it remains largely elusive about the occurrence of mitochondrial iron overload and its significance during cardiac hypertrophy. In the present study, we aim to investigate the role of NCOA4-mediated ferritinophagy and SFXN1-dependent mitochondria iron overload in apelin-13-induced cardiomyocytes hypertrophy. Apelin-13 significantly promotes ferric citrate (FAC)-induced total cellular and mitochondria ion production, as well as mitochondria ROS contents. Mechanistically, apelin-13 effectively induces the expression of SFXN1, a mitochondria iron transporting protein and NCOA4, a cargo receptor of ferritinophagy in dose and time-dependent manner. Conversely, blockade of APJ by F13A abolishes these stimulatory effects. In addition, apelin-13-triggered mitochondria iron overload is reversed by the genetic inhibition of SFXN1 and NCOA4. NCOA4 deficiency via its silencing also interferes with the enhanced expression of SFXN1 evoked by apelin-13. In apelin-13-treated H9c2 cells, the promotion in cell diameter, volume as well as protein contents are obviously suppressed by the knockdown of NCOA4 and SFXN1 with their corresponding siRNAs. Remarkably, the human and murine hypertrophic hearts models, as well as apelin-13-injected mice models, present evident cardiac mitochondrial iron deposition and raised expressions of NCOA4 and SFXN1. Taken together, these results provide experimental evidences that NCOA4-mediated ferritinophagy might be defined as an essential mechanism leading to apelin-13-cardiomyocytes hypertrophy in SFXN1-dependent mitochondria iron overload manners.

Function and regulation of apelin/APJ system in digestive physiology and pathology.

Apelin is an endogenous ligand of seven-transmembrane G-protein-coupled receptor APJ. Apelin and APJ are distributed in various tissues, including the heart, lung, liver, kidney, and gastrointestinal tract and even in tumor tissues. Studies show that apelin messenger RNA is widely expressed in gastrointestinal (GI) tissues, including stomach and small intestine, which is closely correlated with GI function. Thus, the apelin/APJ system may exert a broad range of activities in the digestive system. In this paper, we review the role of the apelin/APJ system in the digestive system in physiological conditions, such as gastric acid secretion, control of appetite and food intake, cell proliferation, cholecystokinin secretion and histamine release, gut-brain axis, GI motility, and others. In pathological conditions, the apelin/APJ system plays an important role in the healing process of stress gastric injury, the clinical features and prognosis of patients with gastric cancers, the reduction of inflammatory response to enteritis and pancreatitis, the mediation of liver fibrogenesis, the promotion of liver damage, the inhibition of liver regeneration, the contribution of splanchnic neovascularization in portal hypertension, the treatment of colon cancer, and GI oxidative damage. Overall, the apelin/APJ system plays diversified functions and regulatory roles in digestive physiology and pathology. Further exploration of the relationship between the apelin/APJ system and the digestive system will help to find new and effective drugs for treating and alleviating the pain of digestive diseases.

CD40L-adjuvanted DNA vaccine carrying EBV-LMP2 antigen enhances anti-tumor effect in NPC transplantation tumor animal.

CD40L, a costimulatory molecule for dendritic cells (DCs) and B cells, can serve as an adjuvant for enhancing the specific immune response induced by DNA vaccine carrying tumor-associated antigens. In this study, we investigated the potential of CD40L as an adjuvant to enhance the anti-tumor effect mediated by a DNA vaccine based on the Epstein-Barr virus-latent membrane protein 2 (EBV-LMP2) antigen. The plasmids capable of expressing the fusion protein EBV-LMP2-CD40L were constructed. Expression vector pVAX1 and plasmid expressing the individual antigen EBV-LMP2 were used as control groups. These plasmids were used to immunize female BALB/c mice (4-6 weeks old) at days 0, 7 and 14. The results suggest that immunization with DNA vaccines carrying fusion gene EBV-LMP2-CD40L can induce specific immunity more effectively than the plasmid expression individual antigen EBV-LMP2. In order to evaluate the anti-tumor effect of this DNA vaccine, we constructed a tumor bearing mouse model. After immunization, the tumor bearing mouse model, DNA vaccination with EBV-LMP2-CD40L plasmid significantly inhibited tumor growth in the tumor bearing mouse model and enhanced the tumor inhibition rate. This study demonstrated that encoding the EBV-LMP2 tumor antigen within an EBV-LMP2-CD40L DNA vaccine generates an effective antitumor response against EBV tumor, which may be a promising method to improve the antitumor immunity of DNA vaccine.

Involvement of the Warburg effect in non-tumor diseases processes.

Warburg effect, as an energy shift from mitochondrial oxidative phosphorylation to aerobic glycolysis, is extensively found in various cancers. Interestingly, increasing researchers show that Warburg effect plays a crucial role in non-tumor diseases. For instance, inhibition of Warburg effect can alleviate pulmonary vascular remodeling in the process of pulmonary hypertension (PH). Interference of Warburg effect improves mitochondrial function and cardiac function in the process of cardiac hypertrophy and heart failure. Additionally, the Warburg effect induces vascular smooth muscle cell proliferation and contributes to atherosclerosis. Warburg effect may also involve in axonal damage and neuronal death, which are related with multiple sclerosis. Furthermore, Warburg effect significantly promotes cell proliferation and cyst expansion in polycystic kidney disease (PKD). Besides, Warburg effect relieves amyloid ß-mediated cell death in Alzheimer's disease. And Warburg effect also improves the mycobacterium tuberculosis infection. Finally, we also introduce some glycolytic agonists. This review focuses on the newest researches about the role of Warburg effect in non-tumor diseases, including PH, tuberculosis, idiopathic pulmonary fibrosis (IPF), failing heart, cardiac hypertrophy, atherosclerosis, Alzheimer's diseases, multiple sclerosis, and PKD. Obviously, Warburg effect may be a potential therapeutic target for those non-tumor diseases.

Stereocomplexation Assisted Assembly of Poly(γ-glutamic Acid)-graft-polylactide Nano-micelles and Their Efficacy as Anticancer Drug Carrier.

BACKGROUND: Micelles as drug carriers are characterized by their inherent instability due to the weak physical interactions that facilitate the self-assembly of amphiphilic block copolymers. As one of the strong physical interactions, the stereocomplexation between the equal molar of enantiomeric polylactides, i.e., the poly(L-lactide) (PLLA) and poly(D-lactide) (PDLA), may be harnessed to obtain micelles with enhanced stability and drug loading capacity and consequent sustained release. AIMS/METHODS: In this paper, stereocomplexed micelles gama-PGA-g-PLA micelles) were fabricated from the stereocomplexation between poly(gama-glutamic acid)-graft-PLLA gama-PGA-g-PLA) and poly(gamaglutamic acid)-graft-PDLA gama-PGA-g-PLA). These stereocomplexed micelles exhibited a lower CMC than the corresponding enantiomeric micelles. RESULT: Furthermore, they showed higher drug loading content and drug loading efficiency in addition to more sustained drug release profile in vitro. In vivo imaging confirmed that the DiR-encapsulated stereocomplexed gama-PGA-g-PLA micelles can deliver anti-cancer drug to tumors with enhanced tissue penetration. Overall, gama-PGA-g-PLA micelles exhibited greater anti-cancer effects as compared with the free drug and the stereocomplexation may be a promising strategy for fabrication of anti-cancer drug carriers with significantly enhanced efficacy.

Peptide-Au Clusters Induced Tumor Cells Apoptosis via Targeting Glutathione Peroxidase-1: The Molecular Dynamics Assisted Experimental Studies.

The original motivation of the article is to give a systematic investigation on the protocol of combining computer simulation and accurate synthesis of serial peptide protected gold clusters for potent tumor targeting therapy. Glutathione peroxidase-1 (GPx-1) is a crucial antioxidant selenoenzyme that regulates cellular redox level, thus becomes a potential target in cancer treatment. We firstly utilize molecular dynamic (MD) simulation to rationally design and screen serial peptide-Au cluster compounds with special peptide sequences and precise gold atoms, which can recognize and bind specific domain of GPx-1 with high affinity. The theoretical simulations were further verified by the following peptide-Au clusters synthesis and GPx-1 activity suppression studies in buffer and cells, respectively. Further cytological experiments corroborated that peptide-Au clusters are promising nanoparticles inducing tumor cells apoptosis by suppressing GPx-1 activity and increasing higher cellular reactive oxygen species level to initiate tumor cell apoptosis through intrinsic mitochondrial pathway.

PAK1-cofilin phosphorylation mediates human lung adenocarcinoma cells migration induced by apelin-13.

Adipocytokines apelin peptide, the ligand of APJ (putative receptor related to the angiotensin receptor AT1), plays key roles in the pathogenesis and deterioration of cancer. In lung cancer, apelin elevating microvessel densities has been reported. Our previous research has characterized that apelin-13 promoted lung adenocarcinoma cell proliferation. However, the effect of apelin on metastasis in lung adenocarcinoma and the underlying mechanisms remain unclear. This study shows that apelin-13 induced human adenocarcinoma cell migration via the APJ receptor. Apelin-13 phosphorylated PAK1 and cofilin increase the migration of lung adenocarcinoma cells. Moreover, the results verify that over-expression of apelin and APJ contributed to reducing the effect of doxorubicin and razoxane on inhibiting lung adenocarcinoma cells metastasis. Hypoxia activated APJ expression and apelin release in lung adenocarcinoma cells. The results demonstrate a PAK1-cofilin phosphorylation mechanism to mediate lung adenocarcinoma cells migration promoted by apelin-13. This discovery further suggests that APJ and its downstream signalling is a potential target for anti-metastatic therapies in lung adenocarcinoma patients.

Peptide-Conjugated Gold Nanoprobe: Intrinsic Nanozyme-Linked Immunsorbant Assay of Integrin Expression Level on Cell Membrane.

Precisely quantifying the membrane protein expression level on cell surfaces is of vital importance for early cancer diagnosis and efficient treatment. We demonstrate that gold nanoparticle bioconjugated by a rationally designed peptide as nanoprobe possesses selective labeling and accurate quantification capacity of integrin GPIIb/IIIa on the human erythroleukemia cell line. Through selective recognition and marking of integrin, two-photon photoluminescence of the nanoprobe is exploited for direct observation of protein spatial distribution on cell membrane. More importantly, utilizing intrinsic enzyme-like catalysis property of the nanoprobe, the expression level of integrin on human erythroleukemia cells can be quantitatively counted in an amplified and reliable colorimetric assay without cell lysis and protein extraction process. In addition, the analysis of the correlation between the gold nanoparticle and the membrane protein via relevant inductively coupled plasma mass spectrometry measurement verifies the reliability of the new analytical method. It is anticipated that this facile and efficient strategy holds a great promise for a rapid, precise, and reliable quantification of interested functional membrane proteins on the cell surface.

Alendronate-decorated biodegradable polymeric micelles for potential bone-targeted delivery of vancomycin.

Osteomyelitis is a bone infection disease which is caused by bacteria or other germs, and could cause serious impact on the health and working capacity of the patients. Alendronate (ALN) can chelate strongly with the calcium ion of hydroxyapatite (HA) which is commonly used to treat osteoporosis. Nanomedicine has attracted a lot of attention in that the nano-sized carrier can deliver drug molecules to specific site of interest with the aid of targeting moiety and achieve sustained release, resulting in improved therapeutic effect and reduced side effect. In this study, micelles self-assembled from poly(lactic acid-co-glycolic acid)-block-poly(ethylene glycol)-alendronate (PLGA-PEG-ALN) copolymer were prepared for bone-targeted delivery of vancomycin (Van). The chemical structure of PLGA-PEG-ALN was confirmed by proton nuclear magnetic resonance ((1)H-NMR) spectroscopy. The formation of the nanoparticles was characterized by dynamic light scattering, transmission electronic microscopy as well as the critical micelle concentration measurement. Release profiles from the micelles revealed that the conjugation of ALN to the surface of micelle did not pose adverse effect on the drug-loading capacity and release behaviors. The cytotoxicity of Van-loaded PLGA-PEG-ALN micelles as well as the blank micelles was evaluated via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay toward rat bone marrow stromal cells (rBMSCs) and human embryonic hepatocytes (L02 cells), and results showed that this Van-loaded micelle possesses appropriate cytotoxicity and is safe in the potential treatment of osteomyelitis. The in vitro affinity of PLGA-PEG-ALN micelles to the HA was also confirmed in vitro. The antibacterial effect of Van-loaded PLGA-PEG-ALN micelles was tested against Staphylococcus aureus (SA) which is the main pathogenic bacteria in osteomyelitis, and the results showed that the Van-loaded micelles can effectively inhibit the growth of SA. These results demonstrated that the PLGA-PEG-ALN micelles may be potentially used for the bone targeted delivery of Van.

The preparation and characterization of micelles from poly(γ-glutamic acid)-graft-poly(L-lactide) and the cellular uptake thereof.

Chemotherapy is a traditional therapeutic approach for the treatment of many solid tumors, but the poor solubility and low bioavailability of hydrophobic anti-cancer drugs greatly limit their applications. In this article, DOX-loaded micelles were fabricated based on an amphiphilic graft polymer composed of hydrophilic poly(γ-glutamic acid) (γ-PGA) and hydrophobic poly (L-lactide) (PLLA). The structure of the copolymers and the characteristic of the micelles were studied. The release profiles of doxorubicin as a model drug from the micelles were measured. Due to the protonation of the amino group of DOX and the conformational alteration of γ-PGA, the release of DOX from γ-PGA-g-PLLA micelle was faster in the acid condition, which is beneficial to tumor therapy. The cellular uptake of the DOX-loaded γ-PGA-g-PLLA micelle was proved to be a GGT-mediated process.

Does cadmium play a physiological role in the hyperaccumulator Thlaspi caerulescens?

The southern French (Ganges) ecotype of Thlaspi caerulescens J & C Presl is able to hyperaccumulate several thousand mg Cd kg(-1) shoot dry weight without suffering from phytotoxicity. We investigated the effect of Cd on growth and the activity of carbonic anhydrase (CA), a typical Zn-requiring enzyme, of T. caerulescens in soil and hydroponic experiments. In one of the hydroponic experiments, T. caerulescens was compared to the non-accumulator Thlaspi ferganense N. Busch. In the soil experiment, additions of Cd at 5-500 mg kg(-1) soil increased the growth of T. caerulescens significantly. In the hydroponic experiments, exposure to Cd at 1-50 microM for three weeks had no significant effect on the growth of T. caerulescens, but decreased the growth of T. ferganense markedly even at the lowest concentration of Cd (1muM). Cadmium exposure significantly increased the CA activity in T. caerulescens, but decreased it in T. ferganense. The CA activity in T. caerulescens correlated positively with the Cd concentration in the shoots up to 6000 mg kg(-1), even though shoot Zn concentration was decreased by the Cd treatments. For comparison, Cd treatments had no consistent effect on the activity of superoxide dismutase in T. caerulescens. The results suggest that Cd may play a physiological role in the Cd-hyperaccumulating ecotype of T. caerulescens by enhancing the activities of some enzymes such as CA. Further research is needed to establish whether a Cd-requiring CA exists in T. caerulescens.