Chondroitin sulfate-based universal nanoparticle delivers angiogenic inhibitor and paclitaxel to exhibit a combination of chemotherapy and anti-angiogenic therapy.

Blocking the tumor nutrient supply through angiogenic inhibitors is an effective treatment approach for malignant tumors. However, using angiogenic inhibitors alone may not be enough to achieve a significant tumor response. Therefore, we recently designed a universal drug delivery system combining chemotherapy and anti-angiogenic therapy to target tumor cells while minimizing drug-related side effects. This system (termed as PCCE) is composed of biomaterial chondroitin sulfate (CS), the anti-angiogenic peptide ES2, and paclitaxel (PTX), which collectively enhance antitumor properties. Interestingly, the PCCE system is conferred exceptional cell membrane permeability due to inherent characteristics of CS, including CD44 receptor-mediated endocytosis. The PCCE could respond to the acidic and high glutathione conditions, thereby releasing PTX and ES2. PCCE could effectively inhibit the proliferation, migration, and invasion of tumor cells and cause apoptosis, while PCCE can affect the endothelial cells tube formation and exert anti-angiogenic function. Consistently, more potent in vivo antitumor efficacy and non-toxic sides were demonstrated in B16F10 xenograft mouse models. PCCE can achieve excellent antitumor activity via modulating angiogenic and apoptosis-related factors. In summary, we have successfully developed an intelligent and responsive CS-based nanocarrier known as PCCE for delivering various antitumor drugs, offering a promising strategy for treating malignant tumors.

Chondroitin sulfate-modified antiangiogenic peptide conjugate induces cell apoptosis via the mitochondria-mediated pathway to perform antitumor activity.

Tumor growth and metastasis heavily rely on angiogenesis, crucial for solid tumor development. Inhibiting angiogenesis associated with tumors emerges as a potent therapeutic approach. Our previous work synthesized the chondroitin sulfate-modified antiangiogenic peptide CS-ES2-AF (CS-EA), which exhibited better antiangiogenic activity, longer half-life, and more robust targeting. In this work, we further evaluated the stability in vitro, cellular uptake mechanism, cell apoptosis mechanism, antitumor activity in vivo, and safety of CS-EA. The stability of CS-EA was consistently superior to that of EA at different temperatures and in different pH ranges. Furthermore, CS-EA mainly entered EAhy926 cells through the clathrin-mediated endocytosis pathway. CS-EA inhibited endothelial cell proliferation, and induced cell apoptosis through downregulating the Bcl-2, reducing mitochondria membrane potential, upregulating cytochrome c, Caspase 3, and reactive oxygen species levels. CS-EA showed better antitumor activity in the B16 xenografted tumor model, with a tumor inhibition rate 1.92 times higher than EA. Simultaneously, it was observed that CS-EA did not cause any harmful effects on the vital organs of the mice. These findings indicate that CS-EA holds significant promise for the treatment of tumors.

Isolation, purification, and antiosteoporosis activity of donkey bone collagen from discarded bone and its antioxidant peptides.

Oxidative stress plays a crucial role in the development of osteoporosis. In this study, it was observed that donkey bone collagen (DC) at a concentration of 500 µg/mL scavenged 17.89 % of 1,1-Diphenyl-2-picrylhydrazyl (DPPH) free radicals, indicating its antioxidant properties. Additionally, when an oxidative damage osteoblast model was created using H2O2, 100 µg/mL DC demonstrated the ability to enhance cell survival by 27.31 %. Furthermore, 50 µg/mL DC increased the intracellular differentiation marker alkaline phosphatase (ALP) level by 62.65 %. Additionally, the study revealed that DC significantly increased the expression of osteoporosis-related factors in serum and effectively restored the abnormal structure of spongy bone in mice osteoporosis model. Peptides (GGWFL, ANLGPA, and GWFK) isolated from DC through gastrointestinal digestion and subsequent enzymatic purification in vitro demonstrated the ability to safeguard osteoblasts from H2O2-induced damage by reducing intracellular reactive oxygen species (ROS). This protection resulted in enhanced cell survival and promoted osteoblast differentiation. This investigation underscores that DC can shield oxidative damage osteoblast model from oxidative stress, ameliorate osteoporosis, and enhance bone density in mice osteoporosis model. These findings suggest various DC applications in the food and medicine industries.

CD44 targeting nanodrug based on chondroitin sulfate for melanoma therapy by inducing mitochondrial apoptosis pathways.

Neovascularization is crucial to the occurrence and progression of tumors, and the development of antiangiogenic drugs has essential theoretical value and clinical significance. However, antiangiogenesis therapy alone cannot meet the needs of tumor therapy. Meanwhile, polysaccharides are ideal drug carriers with promising applications in drug modification and delivery. In this research, we developed a novel redox and acid sensitive nanodrug (CDDP-CS-Cys-EA, CCEA) composed of chondroitin sulfate (CS), antiangiogenic peptide (endostatin2-alft1, EA) and chemotherapeutic drug (cisplatin, CDDP). CCEA exhibited redox and acid responsiveness, better blood hemocompatibility (hemolysis rate < 5 %), the ability to target tumors (CD44-mediated endocytosis), and strong antiangiogenesis and antitumor characteristics in vitro. Moreover, CCEA showed excellent antitumor activity and low toxicity in B16 xenograft mice. It also has been confirmed that CCEA induced tumor cell apoptosis through promoting the expression of Bax, suppressing the expression of Bcl-2, decreasing mitochondrial membrane potential, releasing cytochrome C (Cyto C), and enhancing the activities of Caspase 9 and Caspase 3. The results of this paper provided a theoretical basis and insight for the development of antitumor drugs.

Review: Application of chitosan and its derivatives in medical materials.

Chitin is a natural polymeric polysaccharide extracted from marine crustaceans, and chitosan is obtained by removing part of the acetyl group (usually more than 60 %) in chitin's structure. Chitosan has attracted wide attention from researchers worldwide due to its good biodegradability, biocompatibility, hypoallergenic and biological activities (antibacterial, immune and antitumor activities). However, research has shown that chitosan does not melt or dissolve in water, alkaline solutions and general organic solvents, which greatly limits its application range. Therefore, researchers have carried out extensive and in-depth chemical modification of chitosan and prepared a variety of chitosan derivatives, which have expanded the application field of chitosan. Among them, the most extensive research has been conducted in the pharmaceutical field. This paper summarizes the application of chitosan and chitosan derivatives in medical materials over the past five years.

Glycol-Split Heparin-Linked Prodrug Nanoparticles Target the Mitochondrion Apparatus for Cancer Metastasis Treatment.

The progression and metastasis of solid tumors rely strongly on neovascularization. However, angiogenesis inhibitors alone cannot meet the needs of tumor therapy. This study prepared a new drug conjugate (PTX-GSHP-CYS-ES2, PGCE) by combining polysaccharides (heparin without anticoagulant activity, GSHP), chemotherapeutic drugs (paclitaxel, PTX), and antiangiogenic drugs (ES2). Furthermore, a tumor-targeted prodrug nanoparticle delivery system is established. The nanoparticles appear to accumulate in the mitochondrial of tumor cells and achieve ES2 and PTX release under high glutathione and acidic environment. It has been confirmed that PGCE inhibited the expression of multiple metastasis-related proteins by targeting the tumor cell mitochondrial apparatus and disrupting their structure. Furthermore, PGCE nanoparticles inhibit migration, invasion, and angiogenesis in B16F10 tumor-bearing mice and suppress tumor growth and metastasis in vitro. Further in vitro and in vivo experiments show that PGCE has strong antitumor growth and metastatic effects and exhibits efficient anti-angiogenesis properties. This multi-targeted nanoparticle system potentially enhances the antitumor and anti-metastatic effects of combination chemotherapy and antiangiogenic drugs.

Raw to charred: Changes of precursors and intermediates and their correlation with heterocyclic amines formation in grilled lamb.

This work aimed to investigate the changes and correlations of precursors, intermediates and heterocyclic amines (HCAs) in lamb during charcoal grilling. 28 chemical compounds were detected by high-performance liquid chromatography and gas chromatography-mass spectrometry in grilled lamb from raw to charred. Results demonstrated the types and contents of HCAs were increased during grilling, of which 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP) was dominant and accounted for 61% at the end of grilling (42 min). Glucose and creatine (P < 0.05) decreased with grilling time, creatinine (P < 0.05) and total free amino acid increased. The types and contents of four intermediates (formaldehyde, acetaldehyde, phenylacetaldehyde, 2,5-dimethylpyrazine) increased during grilling. Glucose, creatine, creatinine, ten free amino acids and four intermediates showed significant correlation to HCAs. Also, the ratios of four precursors were significantly correlated with HCAs (P < 0.05), besides creatine/glucose ratio. These results suggested that the time of charcoal grilling should not exceed 14 min at 145 °C in order to reduce the formation of harmful compounds in lamb meat.

A Review of Bioactive Peptides: Chemical Modification, Structural Characterization and Therapeutic Applications.

In recent years, the development and applications of protein drugs have attracted extensive attention from researchers. However, the shortcomings of protein drugs also limit their further development. Therefore, bioactive peptides isolated or simulated from protein polymers have broad application prospects in food, medicine, biotechnology, and other industries. Such peptides have a molecular weight distribution between 180 and 1000 Da. As a small molecule substance, bioactive peptide is usually degraded by various enzymes in the organism and have a short half-life. At the same time, such substances have poor stability and are difficult to produce and store. Therefore, these active peptides may be modified through phosphorylation, glycosylation, and acylation. Compared with other protein drugs, the modified active peptides are more easily absorbed by the body, have longer half-life, stronger targeting, and fewer side effects in addition to higher bioavailability. In the light of their functions, bioactive peptide can be divided into antimicrobial, anti-tumour, anti-angiogenic, antioxidant, anti-fatigue, and anti-hypertensive peptides. This article mainly focuses on the introduction of several promising biologically active peptides functioning as antimicrobial, anti-tumour, antiangiogenic, and antioxidant peptides from the three aspects modification, structural characteristics and mechanism of action.

Improved Stability and Enhanced Anti-Tumor Activity of Hyaluronic Acid Modified ES2-AF Nanoparticle-Like Conjugate.

The growth, migration and spread of malignant tumors requires a large number of new blood vessels to supply nutrients. In our previous study, it was found that the hyaluronic acid (HA) modified novel antiangiogenic peptide ES2-AF has better solubility, longer half-life, stronger targeting than non-modified ES2-AF, and it significantly inhibited the formation of new blood vessels. In the current work, we studied the stability of ES2-AF after HA modification, including heat stability, longterm stability, and pH stability. After treatment with HA-ES2-AF, cell apoptosis and the cell cycle were analyzed using flow cytometry. The inhibitory effect of HA-ES2-AF on tumors was investigated in vivo in HepG2 tumor-bearing nude mice. All the above results showed that HA-ES2-AF significantly improved stability, effectively induced apoptosis of endothelial cells, caused G1 phase arrest of endothelial cells, and decreased the percentage of cells in G2 and S phases. In vivo, HA-ES2-AF exhibited an inhibitory effect on tumors growth. In addition, the results provide a reliable basis for studying the inhibition of neovascularization and anti-tumor drugs in the future.

[Influence of the position of double-lumen endobronchial tube on the efficacy of lung separation and ventilation].

OBJECTIVE: To observe the incidence of double-lumen endobronchial tubes (DLT) malposition caused by body position change or surgical manipulation and its impact on the efficacy of lung separation and ventilation. METHODS: Totally 688 patients undergoing thoracic surgery were enrolled in this study. The patients were intubated with Mallinckrodt DLT following intravenous anesthesia induction. The DLT position was corrected with fiberoptic bronchoscope (FOB), and successful lung separation and satisfactory ventilation were ensured during one-lung ventilation in the supine position. Bronchoscopy was performed immediately and the DLT position was corrected 15 minutes after dependent lung ventilation in the lateral position or in case of ineffective lung separation or SpO(2) declination to below 90%. RESULTS: DLT malposition occurred after lateralization in 112 (16.3%) patients, of whom 12.8% developed hypoxemia and 3.3% encountered air leak. The incidence of left-sided DLT malposition after lateralization was higher than that of right-sided DLT malposition (19.7% vs 12.2%, P<0.01). DLT malposition occurring in 112 patients after lateralization reoccurred in 16 (14.3%) patients during surgery, and the malposition incidence was significantly higher than that of malposition occurring only during surgery (1.2%, P<0.01). CONCLUSION: Malposition of Mallinckrodt double-lumen tubes for lung separation during thoracic anesthesia occurs in 16.3% patients when shifting to lateral position, may reoccur in 14.3% of the patients despite previous FOB positioning.