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.

The experiences of frontline nurses in Wuhan: A qualitative analysis of nurse online diaries during the COVID-19 pandemic.

AIMS AND OBJECTIVE: To explore the experiences of frontline nurses through analyzing nurse online diaries during the pandemic. BACKGROUND: Over 42,600 healthcare professionals took care of patients with COVID-19 in Wuhan in the initial months between 23 January 2020 and 8 April 2020. Many used to write online diaries on Sina Microblog and still wrote about their experiences in the front line on this site. However, there has been little research on frontline nurses' experiences in the initial months of the pandemic through analyzing their narratives. DESIGN: A qualitative descriptive design. METHODS: A qualitative content analysis was used to analyze online diaries written by frontline nurses in Wuhan. A total of 205 entries in online diaries were collected from 12 frontline nurses, as accessible to those who subscribed to Sina Microblog social media site, between 23 January 2020 and 8 April 2020. NVivo12 was used to help analyze the data, and COREQ reporting guidelines were also used in this study. RESULTS: Two themes were identified: constructing a better self and constructing a strong support network. A better self was constructed in describing positive emotions, commitment to care, pride and achievements, and whole-person growth. A strong support network was constructed through social support via different sources and gaining self-support via narrating their personal experiences in diaries. CONCLUSIONS: Frontline nurses demonstrated personal growth, psychological well-being, and professionalism in the process of constructing a better self and a strong support network. RELEVANCE TO CLINICAL PRACTICE: The findings indicate that frontline nurses can use narratives as debriefing opportunities and a way of gaining self-support. We suggest that online communities of professional support be used as an essential platform for sharing narratives and gaining a more comprehensive understanding of frontline nurses in the COVID-19 pandemic and other global public health events.

"I Have Some Sense of Loss but More Sense of Self": A Qualitative Content Analysis of Chinese University Emerging Adults' Personal Life Stories.

The longitudinal, qualitative study aimed to explore the lived experiences of Chinese university emerging adults by analyzing their personal life stories, reflective journals, and semi-structured interview data collected over a 2-year period. A qualitative content analysis was used to identify five themes: maturity, academic performance, interpersonal communication skills, social support network, and sense of loss. The study found that the growth in emerging adulthood was dynamic, positive, and multifaceted. The study demonstrated that writing personal life stories, as a practice of meaningful literacy instruction in EFL contexts, helped students to record a memorable past, reconcile with the past, and strive for personal growth. These findings suggest that emerging adults' personal growth be stressed in foreign language teaching to promote Chinese university emerging adults' growth and development. It is also suggested that personal life stories be used in foreign language teaching under the guidance of meaningful literacy instruction.