Membrane Disruption-Enhanced Photodynamic Therapy against Gram-Negative Bacteria by a Peptide-Photosensitizer Conjugate.

Photodynamic therapy (PDT) emerges as a promising strategy for combating bacteria with minimal drug resistance. However, a significant hurdle lies in the ineffectiveness of most photosensitizers against Gram-negative bacteria, primarily attributable to their characteristic impermeable outer membrane (OM) barrier. To tackle this obstacle, we herein report an amphipathic peptide-photosensitizer conjugate (PPC) with intrinsic outer membrane disruption capability to enhance PDT efficiency against Gram-negative bacteria. PPC is constructed by conjugating a hydrophilic ultrashort cationic peptide to a hydrophobic photosensitizer. PPC could efficiently bind to the OM of Gram-negative bacteria through electrostatic adsorption, and subsequently disrupt the structural integrity of the OM. Mechanistic investigations revealed that PPC triggers membrane disruption by binding to both lipopolysaccharide (LPS) and phospholipid leaflet in the OM, enabling effective penetration of PPC into the Gram-negative bacteria interior. Upon light irradiation, PPC inside bacteria generates singlet oxygen not only to effectively decrease the survival of Gram-negative bacteria P. aeruginosa and E. coli to nearly zero in vitro, but also successfully cure the full-thickness skin infection and bacterial keratitis (BK) induced by P. aeruginosa in animal models. Thus, this study provides a broad-spectrum antibacterial phototherapeutic design strategy by the synergistic action of membrane disruption and PDT to combat Gram-negative bacteria.

The diagnosis of tuberculous meningitis: advancements in new technologies and machine learning algorithms.

Tuberculous meningitis (TBM) poses a diagnostic challenge, particularly impacting vulnerable populations such as infants and those with untreated HIV. Given the diagnostic intricacies of TBM, there's a pressing need for rapid and reliable diagnostic tools. This review scrutinizes the efficacy of up-and-coming technologies like machine learning in transforming TBM diagnostics and management. Advanced diagnostic technologies like targeted gene sequencing, real-time polymerase chain reaction (RT-PCR), miRNA assays, and metagenomic next-generation sequencing (mNGS) offer promising avenues for early TBM detection. The capabilities of these technologies are further augmented when paired with mass spectrometry, metabolomics, and proteomics, enriching the pool of disease-specific biomarkers. Machine learning algorithms, adept at sifting through voluminous datasets like medical imaging, genomic profiles, and patient histories, are increasingly revealing nuanced disease pathways, thereby elevating diagnostic accuracy and guiding treatment strategies. While these burgeoning technologies offer hope for more precise TBM diagnosis, hurdles remain in terms of their clinical implementation. Future endeavors should zero in on the validation of these tools through prospective studies, critically evaluating their limitations, and outlining protocols for seamless incorporation into established healthcare frameworks. Through this review, we aim to present an exhaustive snapshot of emerging diagnostic modalities in TBM, the current standing of machine learning in meningitis diagnostics, and the challenges and future prospects of converging these domains.

Development of organic photosensitizers for antimicrobial photodynamic therapy.

Bacterial infection poses a significant threat to human health, and the emergence of antibiotic-resistant strains has exacerbated the situation. Antimicrobial photodynamic therapy (aPDT) has emerged as a promising antibiotic-free treatment option that employs reactive oxygen species (ROS) to cause oxidative damage to bacteria and surrounding biomolecules for treating microbial infections. This review summarizes the recent progress in the development of organic photosensitizers, including porphyrins, chlorophyll, phenothiazines, xanthenes and aggregation-induced emission photosensitizers, for aPDT. A detailed description of innovative therapeutic strategies that rely on the infection microenvironment or the unique structural properties of bacteria to amplify the therapeutic effects is provided. Moreover, the combination of aPDT with other therapy strategies such as antimicrobial peptide therapy, photothermal therapy (PTT) or gas therapy, is described. Finally, the current challenges and perspectives of organic photosensitizers for clinical antibacterial applications are discussed.

Docetaxel-induced cognitive impairment in rats can be ameliorated by edaravone dexborneol: Evidence from the indicators of biological behavior and anisotropic fraction.

Objective: This study aimed to investigate the effect of Edaravone Dexborneol (ED) on impaired learning and memory in docetaxel (DTX)-treated rats using cognitive behavior assessments and magnetic resonance diffusion tensor imaging (DTI). Materials and methods: In total, 24 male Sprague-Dawley rats were divided into control, low-dose DTX (L-DTX) model, and high-dose DTX(H-DTX) model groups, with eight rats in each group, numbered 1-8. The rats were intraperitoneally injected with 1.5 mL of either normal saline (control group), or 3 mg/kg and 6 mg/kg DTX (L-DTX and H-DTX groups, respectively), once a week for 4 weeks. The learning and memory abilities of each group were tested using a water maze. At the end of the water maze test, rats 1-4 in each group were treated with ED (3 mg/kg, 1 mL), and rats 5-8 were injected with an equal volume of normal saline once a day for 2 weeks. The learning and memory abilities of each group were evaluated again using the water maze test, and the image differences in the hippocampus of each group were analyzed using DTI. Results: (1) H-DTX group (32.33 ± 7.83) had the longest escape latency, followed by the L-DTX group (27.49 ± 7.32), and the Control group (24.52 ± 8.11) having the shortest, with the difference being statistically significant (p < 0.05). (2) Following ED treatment, compared to rats treated with normal saline, the escape latency of the L-DTX (12.00 ± 2.79 vs. 10.77 ± 3.97, p < 0.05), and the H-DTX (12.52 ± 3.69 vs. 9.11 ± 2.88, p < 0.05) rats were significantly shortened. The residence time in the target quadrant of H-DTX rats was significantly prolonged (40.49 ± 5.82 vs. 55.25 ± 6.78, p < 0.05). The CNS damage in the L-DTX rats was repaired to a certain extent during the interval between the two water maze tests (28.89 ± 7.92 vs. 12.00 ± 2.79, p < 0.05). (3) The fractional anisotropy (FA) value of DTI in the hippocampus of rats in the different groups showed variable trends. After treatment with ED, though the FA values of most areas in the hippocampus of rats in L-DTX and H-DTX groups were higher than before, they did not reach the normal level. Conclusion: ED can ameliorate the cognitive dysfunctions caused by DTX in rats by improving the learning and memory impairment, which is reflected in the recovery of biological behavior and DTI indicators of the hippocampus.

Negative effects of abamectin on soil microbial communities in the short term.

With the widespread use of abamectin in agriculture, there is increasing urgency to assess the effects of abamectin on soil microorganisms. Here, we treated plant-soil microcosms with abamectin at concentrations of 0.1 and 1.0 mg/kg and quantified the impacts of abamectin on bulk and rhizosphere soil microbial communities by shotgun metagenomics after 7 and 21 days of exposure. Although abamectin was reported to be easily degradable, it altered the composition of the soil microbial communities, disrupted microbial interactions, and decreased community complexity and stability after 7 days of exposure. After treatment with abamectin at a concentration of 1.0 mg/kg, some opportunistic human diseases, and soil-borne pathogens like Ralstonia were enriched in the soil. However, most ecological functions in soil, particularly the metabolic capacities of microorganisms, recovered within 21 days after abamectin treatment. The horizontal and vertical gene transfer under abamectin treatments increased the levels of antibiotic resistance genes dissemination. Overall, our findings demonstrated the negative effects of abamectin on soil ecosystems in the short-term and highlight a possible long-term risk to public and soil ecosystem health associated with antibiotic resistance genes dissemination.

Dimeric Artesunate Glycerophosphocholine Conjugate Nano-Assemblies as Slow-Release Antimalarials to Overcome Kelch 13 Mutant Artemisinin Resistance.

Current best practice for the treatment of malaria relies on short half-life artemisinins that are failing against emerging Kelch 13 mutant parasite strains. Here, we introduce a liposome-like self-assembly of a dimeric artesunate glycerophosphocholine conjugate (dAPC-S) as an amphiphilic prodrug for the short-lived antimalarial drug, dihydroartemisinin (DHA), with enhanced killing of Kelch 13 mutant artemisinin-resistant parasites. Cryo-electron microscopy (cryoEM) images and the dynamic light scattering (DLS) technique show that dAPC-S typically exhibits a multilamellar liposomal structure with a size distribution similar to that of the liposomes generated using thin-film dispersion (dAPC-L). Liquid chromatography-mass spectrometry (LCMS) was used to monitor the release of DHA. Sustainable release of DHA from dAPC-S and dAPC-L assemblies increased the effective dose and thus efficacy against Kelch 13 mutant artemisinin-resistant parasites in an in vitro assay. To better understand the enhanced killing effect, we investigated processes for deactivation of both the assemblies and DHA, including the roles of serum components and trace levels of iron. Analysis of parasite proteostasis pathways revealed that dAPC assemblies exert their activity via the same mechanism as DHA. We conclude that this easily prepared multilamellar liposome-like dAPC-S with long-acting efficacy shows potential for the treatment of severe and artemisinin-resistant malaria.

Comparison of the Fermentation Activities and Volatile Flavor Profiles of Chinese Rice Wine Fermented Using an Artificial Starter, a Traditional JIUYAO and a Commercial Starter.

In this study, an artificial starter culture was prepared using the core microbial species of JIUYAO to produce Chinese rice wine (CRW). The fermentation activity and flavor profiles of CRW samples fermented with traditional JIUYAO, a commercial starter culture, and our artificial starter culture were compared. The optimal protectant combination for lyophilization of the artificial starter was established as 15.09% skim milk, 4.45% polyethylene glycol, 1.96% sodium glutamate, and 11.81% maltodextrin. A comparative analysis revealed that the ethanol content of the three CRW samples was similar. The total acid content of the CRW sample fermented with the artificial starter (7.10 g/L) was close to that of the sample fermented with JIUYAO (7.35 g/L), but higher than that of the sample fermented with the commercial starter (5.40 g/L). An electronic nose analysis revealed that the olfactory fingerprints of the CRW samples fermented with JIUYAO and the artificial starter resembled each other. For both above mentioned samples, the flavor profiles determined by gas chromatography-mass spectrometry indicated some differences in the variety and content of the aroma compounds, but the key odorants (odor activity values ≥1), such as isoamyl acetate, ethyl acetate, phenyl alcohol, and isoamyl alcohol, were similar.

Meta-transcriptomic profiling of functional variation of freshwater microbial communities induced by an antidepressant sertraline hydrochloride.

Sertraline hydrochloride (Ser-HCl) is an effective and commonly used antidepressant drug, which is also frequently detected in aquatic environments. Our previous research showed that Ser-HCl changes the community composition of aquatic microbiome, but the understanding of the expression of functional pathways in microbial communities is still incomplete; to address this knowledge gap, we used meta-transcriptomics analysis to evaluate the toxicity of Ser-HCl to natural aquatic microbial communities cultured in laboratory microcosms. Meta-transcriptomic results show that a 15-day exposure to 50 µg/L Ser-HCl significantly changed the functional expression activity of aquatic microbial communities. Pathways related to lipid metabolism, energy metabolism, membrane transport function, and genetic information processing in the aquatic microbial community were severely inhibited under Ser-HCl treatment, but metabolism of cofactors and vitamins to alleviate biological toxicity after Ser-HCl exposure was enhanced. Our study thus reveals details of the effects of sertraline on the functioning of aquatic microbiome. Due to the extensive use of Ser-HCl and its strong biological activity, it should not continue to be an overlooked pollutant. Therefore, more attention should be paid to the negative effects of such biologically active drugs on the expression of aquatic microbiome.

Lipoic acid modified antimicrobial peptide with enhanced antimicrobial properties.

RIWVIWRR-NH2 (Bac8c) is a natural antimicrobial peptide (AMP) exhibiting great antibacterial activity against Gram-negative and Gram-positive bacteria. In this work, lipoic acid was used as a fatty acid hydrophobic ligand to modify Bac8c (LA-Bac8c) to further improve its antimicrobial properties. Minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) assays showed that LA-Bac8c exhibited lower MIC (MBC) values against Staphylococcus aureus (S. aureus) and methicillin-resistant Staphylococcus aureus (MRSA) than Bac8c. Similar results were reflected in the antibiofilm activity towards S. aureus and MRSA, and LA-Bac8c showed better activity to the biofilm which has been formed or is being formed. In addition to this, the obvious interaction between bacteria/biofilm and LA-Bac8c was observed by microscopy. LA-Bac8c displayed strong membrane depolarization and outer membrane permeabilizing ability, and the cell membrane treated with LA-Bac8c was destroyed to the leakage of bacteria cellular components. All these data indicated LA-Bac8c could be used as a useful antimicrobial peptide with wide application prospect.

Evaluation of the Perceptual Interactions among Aldehydes in a Cheddar Cheese Matrix According to Odor Threshold and Aroma Intensity.

To evaluate the contributions of 3-methylbutanal, 2-methylbutanal, 2-methylpropanal, and benzaldehyde in cheddar cheese models, the threshold values, optimal concentration ranges, and perceptual actions of these compounds were determined at various concentrations. The thresholds for 3-methylbutanal, 2-methylbutanal, 2-methylpropanal, and benzaldehyde in the cheese matrix were 150.31, 175.39, 150.66, and 500.21 µg/kg, respectively, which were significantly higher than the corresponding values in water. The optimal concentration ranges of these aldehydes were determined as 150-300, 175-325, 150-350, and 500-1500 µg/kg, respectively. Based on the results of the threshold method and Feller's model, five binary mixtures were found to have synergistic effects, and only the pair of 2-methylpropanal and benzaldehyde was determined to have a masking effect. In addition, the synergistic olfactory effects between the four ternary mixtures and the quaternary mixture of these aldehydes were also assesSsed using Feller's model. In a σ-τ plot analysis, synergism was usually observed when these odor pairs were at their threshold levels. In summary, the results suggested that perceptual interactions among these aldehydes exist in a cheese model variably with different concentrations and threshold ratios. This study will be helpful to a further understanding of the nutty aroma and improving the aroma quality of cheddar cheese.

Core-crosslinked nanomicelles based on crosslinkable prodrug and surfactants for reduction responsive delivery of camptothecin and improved anticancer efficacy.

As an important DNA topoisomerase I inhibitor in oncotherapy, camptothecin (CPT) with traditional formulation only shows a limited clinical application mainly because of its poor solubility. In this study, a novel redox responsive nanoscaled delivery system was developed to overcome the inherent defect of CPT. Firstly, a CPT prodrug (CPT-LA) and two crosslinkable surfactants (SO-LA and MPEG-LA) was synthesized, all of which contained the same lipoic acid (LA) structure. In the preparation, highly core-crosslinked structure was formed by adding a thiol crosslinker, which can induce LA ring opening polymerization and disulfide crosslinking. The resulting CPT-LA core-crosslinked nanomicelles (CPT-LA CNM) were formulated with a highly crosslinked core and a PEG hydrophilic shell. Dynamic light scattering (DLS) characterization indicated that CPT-LA CNM possessed a narrow size distribution (184.6 ± 3.6 nm) and negatively charged zeta potential (-3.5 ± 1.2 mV). The storage and physiological stabilities showed that the size distribution of CPT-LA CNM was relatively stable in both conditions which were neutral PBS at 4 °C (1 week period) and PBS containing 10% serum at 37 °C (24 h period). Moreover, the effective CPT release behavior of CPT-LA CNM was confirmed in the reducing circumstances containing dithiothreitol (DTT). Under confocal laser scanning microscopy (CLSM), CPT-LA CNM demonstrated a rapid cellular uptake behavior against cancer cells when compared to CPT suspension. Finally, the enhanced anticancer efficacy of CPT-LA CNM was also detected by in vitro cytotoxicity and cell apoptosis assay. In summary, the core-crosslinked CPT-LA CNM could be a promising CPT delivery system because of high stability, effectively controlled release as well as improved anticancer activity.

Improved Antitumor Activity of Novel Redox-Responsive Paclitaxel-Encapsulated Liposomes Based on Disulfide Phosphatidylcholine.

The microtubule inhibitor paclitaxel (PTX) is used to treat a wide range of solid tumors. Due to the poor aqueous solubility of PTX, a continuous demand for safe, efficient PTX formulations with improved antitumor activity exists. Here, we report a novel form of redox-sensitive paclitaxel (PTX)-encapsulated liposomes based on the previously developed disulfide phosphatidylcholine (SS-PC). PTX-loaded stealth liposomes (PTX/SS-LP) composed of SS-PC, 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-PEG2000 (DSPE-PEG2000), and cholesterol were prepared using the reverse-phase evaporation method. The characterization of the PTX/SS-LP liposomes using dynamic light scattering and transmission electron microscopy confirmed their uniform particle size and typical unilamellar vesicle structure with an average bilayer thickness of approximately 4 nm. Changes in the size and morphology as well as the rapid release of PTX triggered by the addition of dithiothreitol revealed the redox sensitivity of PTX/SS-LP. Finally, evaluations in MCF-7 and A549 cells in vitro and in BALB/c mice in vivo revealed the improved anticancer efficiency, biodistribution, and safety of PTX/SS-LP compared with those of Taxol and nonredox-sensitive PTX/LP. In conclusion, PTX/SS-LP displays a redox-responsive release of paclitaxel with improved antitumor activity and has great potential as a next-generation stealth liposomal PTX delivery system.

Redox-sensitive dimeric camptothecin phosphatidylcholines-based liposomes for improved anticancer efficacy.

Aim: A redox-triggered camptothecin (CPT) liposomal system was developed for an improved clinical potential in tumor therapy. Materials & methods: CPT-phosphorylcholine conjugates (CPT-SS-GPCs: CPT-SS-3-GPC and CPT-SS-11-GPC) were synthesized by conjugating CPT to glycerylphosphorylcholine via disulfide bond linker. CPT-SS-GPCs could be assembled into liposomes. Different in vitro and in vivo analyses were used to evaluate the anticancer activities of CPT-SS-GPCs. Results: CPT-SS-GPCs liposomes exhibited extremely high drug loading and uniform size of 150-200 nm. Moreover, the rapid release of parent CPT in reductive condition and high cellular uptake of CPT-SS-GPCs liposomes were observed. At last, in vitro and in vivo anticancer assay showed the enhanced efficacy of CPT-SS-GPCs liposomes. Conclusion: Redox-triggered CPT-SS-GPC liposomes have great potential in tumor therapy.

Thiol-Mediated Multidentate Phosphorylcholine as a Zwitterionic Ligand for Stabilizing Biocompatible Gold Nanoparticles.

The increasing application of gold nanoparticles (AuNPs) in biomedicine requires extensive investigation of surface modification and stabilization to maximize their advantages for the diversity of more challenging biological utilization. Herein, a thiol-mediated multifunctional phospholipid ligand was designed while disclosing a zwitterionic nature to AuNPs. The ligand was synthesized by attachment to two bidentate lipoic acid (LA) anchor groups and incorporation of a zwitterionic phosphatidylcholine (PC) group, allowing for excellent hydrophilicity. As demonstrated through ultraviolet-visible spectroscopy, appropriate 7 nm diameter AuNPs modified with a 1,2-dilipoyl-sn-glycero-3-phosphorylcholine (di-LA-PC) compact ligand exhibited the best colloidal stability in a high NaCl concentration of up to 217 mM, different temperatures, and a wide range of pH values from 3 to 11 when compared to the traditional surfactants or thiol-contained amino acid surface modification cases. These AuNPs are also stable without specific interaction to positively/negatively charged proteins, possibly leading to prolonged blood circulation after in vivo administration. Moreover, much more resistance to ligand competition of dithiothreitol was found than other thiol-coated AuNPs, which further highlighted their affinity in an aqueous system. Biocompatibility of the zwitterionic ligand di-LA-PC-modified AuNPs was finally evaluated by hemolysis and cytotoxicity tests. Cumulatively, the remarkable stability and biocompatibility of AuNPs, multicoordinated with a di-LA-PC ligand, potentially motivated them as a practical alternative for surface tailoring in biotechnology.

Thioether Phosphatidylcholine Liposomes: A Novel ROS-Responsive Platform for Drug Delivery.

Liposomes are the most valuable nanocarriers in clinical use because of their biocompatibility, biodegradation, and effective encapsulation of hydrophilic or hydrophobic drugs. However, their applications are limited by the structure and functions of the most common phospholipids used as the main component of the liposomes. In this work, novel series of thioether phosphatidylcholines (S-PCs) and S-PC-based liposomes (S-LPs) were developed for reactive oxygen species (ROS)-responsive drug release. First of all, S-PCs with different chain lengths were synthesized by a combination of click reaction and heterogeneous esterification. Differential scanning calorimetry studies indicated that S-PCs had different phase transition temperatures depending on their chain lengths. Their critical aggregation concentrations were measured by the fluorescence probe technique indicating the self-assembly ability. After that, S-PC-based stealth liposomes (S-LPs) containing DSPE-PEG2000 and cholesterol were prepared via a classic thin-film method. Doxorubicin (DOX) as a model drug was loaded in the stealth liposomes (DOX/S-LPs) by using the ammonium sulfate gradient method with high encapsulation efficiency. DOX/S-LPs were characterized by dynamic light scattering (DLS), transmission electron microscope (TEM), and cryogenic TEM, confirming their spherical structure with the bilayer thickness of about 4 nm. The ROS sensitivity of S-PCs and S-LPs was carefully evaluated in the presence of H2O2 by means of mass spectrometry, DLS, TEM, and ultraviolet spectroscopy and release study. The results indicated the significant structural change of S-LPs after H2O2 treatment, which demonstrated that S-LPs possessed an efficient ROS-triggered disintegration because of thioether oxidation of S-PCs. Finally, in vitro and in vivo anticancer efficiency assays revealed the improved drug potency of DOX/S-LPs, which can be attributed to ROS-triggered destruction of S-LPs after the uptake by tumor cells followed by rapid release of DOX. All together, as alternatives of traditional phosphatidylcholines, S-PC-based stealth liposomes are promising ROS-responsive carriers for the controlled delivery of drugs.

Disulfide phosphatidylcholines: alternative phospholipids for the preparation of functional liposomes.

Phosphatidylcholine is the main component of liposomes and other phospholipid-based nanocarriers in drug delivery. However, the functions and applications of these nanocarriers are extremely limited by conventional phospholipids. Here we report novel disulfide phosphatidylcholines (SS-PCs) and SS-PC based liposomes (SS-LPs) used as alternatives to traditional phospholipids and liposomes.

Ultrashort Lipopeptides Self-Assembled with Gold Nanoparticles as Potent Antimicrobial Agents.

To develop new antimicrobial synthetic lipopeptides with optimizing peptide length, cationic tripeptides RWR/WRR were N-terminal fatty acylated, and self-assembled with 1-dodecanethiol-anchored gold nanoparticles (Au-DT NPs) via hydrophobic interaction. The ultrashort lipopeptides and their nano-assemblies were effective against a variety of microorganisms, with minimal inhibitory concentrations ranging from 0.5 to 8 µg/mL. Hemolysis analysis and in vitro cytotoxicity assay revealed that self-assembling with Au-DT NPs would improve biological toxicity of lipopeptides, especially for the most active lipopeptides (Palmitoyl-RWR, Palmitoyl-WRR) with long lipid tails. As lipopeptides/ Au-DT NPs displayed slower bactericidal kinetics compared with free lipopeptides, the mode of action was further investigated. Difference in membrane targeting mechanism between lipopeptides and their nano-assemblies may be attributed to the structural architecture. The simple composition and diverse specificities of lipopeptides/Au-DT NPs, as well as their biocompatibility could make them as economically available potent antimicrobial agents for various applications.

Redox sensitive lipid-camptothecin conjugate encapsulated solid lipid nanoparticles for oral delivery.

Camptothecin (CPT) is an important topoisomerase I enzyme (Topo I) targeting anti-cancer drug, but its oral administration is limited by poor bioavailability and severe side effects. In this study, a redox sensitive CPT prodrug loaded solid lipid nanoparticles (SLN) system for oral delivery was developed. First of all, CPT-palmitic acid conjugate via a cleavable disulfide bond linker (CPT-SS-PA) was synthesized and encapsulated into SLN. The drug release of SLN was evaluated in neutral environment, simulated gastrointestinal fluid and reductive solution. The results indicated that CPT-SS-PA SLN maintained chemical structural stability in simulated physiological environment but exhibited quick reduction-response release of CPT in the presence of dithiothreitol. Furthermore, in vitro cytotoxicity of CPT-SS-PA SLN was tested against cancer cell lines, and the cellular uptake behavior for oral delivery was checked by confocal laser scanning microscopy (CLSM) using Caco-2 cells model. From the data, CPT-SS-PA SLN revealed high anti-cancer activity and enhanced Caco-2 cell absorption. Finally, the oral bioavailability and intestinal safety of CPT-SS-PA SLN were preliminary evaluated by in vivo pharmacokinetic and histopathological study, respectively. This study demonstrated that CPT-SS-PA SLN could be developed as an effective CPT oral delivery system due to its enhanced oral bioavailability and reduced intestinal side effect.

The prognostic value of C-X-C motif chemokine receptor 4 in patients with sporadic malignant peripheral nerve sheath tumors.

BACKGROUND: Recent studies indicate that C-X-C motif chemokine receptor 4 (CXCR4) and its ligand, C-X-C motif chemokine ligand 12 (CXCL12), stimulate expression of the cell cycle regulatory protein Cyclin D1 in neurofibromatosis 1-associated malignant peripheral nerve sheath tumor (MPNST) cells and promote their proliferation. In this study, we measured the expression of CXCR4, CXCL12, and Cyclin D1 proteins in sporadic MPNST tissues from Chinese patients and investigated their prognostic values. METHODS: CXCR4, CXCL12, and Cyclin D1 protein expression in samples from 58 Chinese patients with sporadic MPNST was assessed with immunohistochemical staining. Their prognostic values were evaluated with Kaplan-Meier analysis and a log-rank test. Multivariate Cox regression analysis was used to identify independent prognostic factors. RESULTS: High expression of CXCR4, CXCL12, and Cyclin D1 was observed in 19 (32.8%), 32 (55.2%), and 16 (27.6%) samples, respectively. CXCR4 expression was positively correlated with CXCL12 expression (r = 0.334, P = 0.010) and Cyclin D1 expression (r = 0.309, P = 0.018). Patients with high CXCR4 expression showed longer overall survival than those with low CXCR4 expression (χ2 = 4.642, P = 0.031). CONCLUSION: High CXCR4 expression may define a specific subtype of sporadic MPNST with favorable prognosis.

Characterization of FGFR signaling pathway as therapeutic targets for sarcoma patients.

The fibroblast growth factor receptor (FGFR) family plays important roles in regulating cell growth, proliferation, survival, differentiation and angiogenesis. Deregulation of the FGF/FGFR signaling pathway has been associated with multiple development syndromes and cancers, and thus therapeutic strategies targeting FGFs and FGFR in human cancer are currently being explored. However, few studies on the FGF/FGFR pathway have been conducted in sarcoma, which has a poor outcome with traditional treatments such as surgery, chemotherapy, and radiotherapy. Hence, in the present review, we provide an overview of the role of the FGF/FGFR pathway signal in sarcoma and FGFR inhibitors, which might be new targets for the treatment of sarcomas according to recent research.