Exosomes are emerging as important mediators of the cross-talk between tumor cells and the microenvironment. However, the mechanisms by which exosomes modulate tumor development under hypoxia in pancreatic cancer remain largely unknown. Here, we found that hypoxic exosomes derived from pancreatic cancer cells activate macrophages to the M2 phenotype in a HIF1a or HIF2a-dependent manner, which then facilitates the migration, invasion, and epithelial-mesenchymal transition of pancreatic cancer cells. Given that exosomes have been shown to transport miRNAs to alter cellular functions, we discovered that miR-301a-3p was highly expressed in hypoxic pancreatic cancer cells and enriched in hypoxic pancreatic cancer cell-derived exosomes. Circulating exosomal miR-301a-3p levels positively associated with depth of invasion, lymph node metastasis, late TNM stage, and poor prognosis of pancreatic cancer. Hypoxic exosomal miR-301a-3p induced the M2 polarization of macrophages via activation of the PTEN/PI3Kγ signaling pathway. Coculturing of pancreatic cancer cells with macrophages in which miR-301a-3p was upregulated or treated with hypoxic exosomes enhanced their metastatic capacity. Collectively, these data indicate that pancreatic cancer cells generate miR-301a-3p-rich exosomes in a hypoxic microenvironment, which then polarize macrophages to promote malignant behaviors of pancreatic cancer cells. Targeting exosomal miR-301a-3p may provide a potential diagnosis and treatment strategy for pancreatic cancer.Significance: These findings identify an exosomal miRNA critical for microenvironmental cross-talk that may prove to be a potential target for diagnosis and treatment of pancreatic cancer.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/16/4586/F1.large.jpg Cancer Res; 78(16); 4586-98. ©2018 AACR.

/pdf/hypoxic-tumor-derived-exosomal-mir-301a-mediates-m2-syz92wuz92.pdf

Hypoxic Tumor-Derived Exosomal miR-301a Mediates M2 Macrophage Polarization via PTEN/PI3Kγ to Promote Pancreatic Cancer Metastasis.

Hypertrophic scarring: the greatest unmet challenge after burn injury.

https://cyberleninka.org/article/n/876404.pdf

ECM and ECM-like materials – Biomaterials for applications in regenerative medicine and cancer therapy

Bleeding complications arising from trauma, surgery, and as congenital, disease-associated, or drug-induced blood disorders can cause significant morbidities and mortalities in civilian and military populations. Therefore, stoppage of bleeding (hemostasis) is of paramount clinical significance in prophylactic, surgical, and emergency scenarios. For externally accessible injuries, a variety of natural and synthetic biomaterials have undergone robust research, leading to hemostatic technologies including glues, bandages, tamponades, tourniquets, dressings, and procoagulant powders. In contrast, treatment of internal noncompressible hemorrhage still heavily depends on transfusion of whole blood or blood's hemostatic components (platelets, fibrinogen, and coagulation factors). Transfusion of platelets poses significant challenges of limited availability, high cost, contamination risks, short shelf-life, low portability, performance variability, and immunological side effects, while use of fibrinogen or coagulation factors provides only partial mechanisms for hemostasis. With such considerations, significant interdisciplinary research endeavors have been focused on developing materials and technologies that can be manufactured conveniently, sterilized to minimize contamination and enhance shelf-life, and administered intravenously to mimic, leverage, and amplify physiological hemostatic mechanisms. Here, a comprehensive review regarding the various topical, intracavitary, and intravenous hemostatic technologies in terms of materials, mechanisms, and state-of-art is provided, and challenges and opportunities to help advancement of the field are discussed.

/pdf/biomaterials-and-advanced-technologies-for-hemostatic-7zfgldaph9.pdf

Biomaterials and Advanced Technologies for Hemostatic Management of Bleeding.

Electrospinning versus microfluidic spinning of functional fibers for biomedical applications.

Biomimetic LBL structured nanofibrous matrices assembled by chitosan/collagen for promoting wound healing

The status of microRNA-21 expression and its clinical significance in human cutaneous malignant melanoma.

To examine the changes in electrolyte concentrations after addition of zeolite-based hemostat QuikClot in blood and the effects of zeolite on blood coagulation in vitro. Fresh blood was taken from healthy adult volunteers and sheep, and the electrolyte concentrations in blood were measured using a blood electrolyte analyzer. Zeolite Saline Solution (ZSS) was prepared by addition of 2 g zeolite to 0.9% NaCl solution (4, 8, or 16 mL). The electrolytes in ZSS were measured using inductively coupled plasma atomic emission spectroscopy. The prothrombin time (PT) and activated partial thromboplastin time (APTT) of blood were measured using the test tube method. The activated clotting time (ACT) and clotting rate (CR) of blood were measured with Sonoclot Coagulation and Platelet Function Analyzer. Addition of zeolite (50 and 100 mg) in 2 mL human blood significantly increased Ca2+ concentration, while Na+ and K+ concentrations were significantly decreased. Addition of zeolite (50 and 100 mg) in 0.9% NaCl solution (2 mL) caused similar changes in Ca2+ and Na+ concentrations. Si4+ (0.2434 g/L) and Al3+ (0.2575 g/L) were detected in ZSS (2 g/8 mL). Addition of ZSS in sheep blood shortened APTT in a concentration dependent manner, without changing PT. ZSS or aqueous solution of CaCl2 that contained Ca2+ concentration identical to that of ZSS significantly shortened ACT in human blood without significantly changing CR, and the effect of ZSS on ACT was not significantly different from that of CaCl2. Zeolite releases Ca2+ into blood, thus accelerating the intrinsic pathway of blood coagulation and shortening the clot formation time.

https://zeolife.gr/wp-content/uploads/2015/03/quikclot.pdf

Zeolite-based hemostat QuikClot releases calcium into blood and promotes blood coagulation in vitro.

Background/Aims: Although microRNA-301a has been reported to function as an oncogene in many human cancers, the roles of miR-301a in malignant melanoma (MM) is unclear. The present study aims to investigate the functional roles of miR-301a in MM and its possible molecular mechanisms. Methods: Quantitative real-time PCR (qRT-PCR) assay was performed to detect the expression of miR-301a in MM tissues, and analyze its correlation with metastasis and prognosis of MM patients. In vitro, miR-301a was ectopically expressed using overexpression and knock-down strategies, and the effects of miR-301a expression on growth, apoptosis, migration, invasion and chemosensitivity of MM cells were further investigated. Furthermore, the potential and functional target gene was identified by luciferase reporter, qRT-PCR, Western blot assays. Results: We showed that the expression of miR-301a was significantly upregulated in MM tissues, and upregulation of miR-301a correlated with metastasis and poor prognosis of MM patients. Transfection of miR-301a/inhibitor significantly inhibited growth, colony formation, migration, invasion and enhanced apoptosis and chemosensitivity in MM cells, while transfection of miR-301a/mimic could induce the inverse effects on phenotypes of MM cells. Luciferase reporter, qRT-PCR and Western blot assays showed that phosphatase and tensin homolog (PTEN) was a direct and functional target of miR-301a. It was also observed that the Akt and FAK signaling pathways were involved in miR-301/PTEN-promoting MM progression. Conclusion: Taken together, our study suggests that miR-301a may be used as a potential therapeutic target in the treatment of human MM.

/pdf/expression-of-microrna-301a-and-its-functional-roles-in-49o2qqmxa8.pdf

Expression of MicroRNA-301a and its Functional Roles in Malignant Melanoma.

This study reports the preparation and properties of a chitosan (CS)–organic rectorite (OREC)/sodium alginate (SA) composite sponge. The novel sponge was fabricated by solution intercalation and chemical cross-linking techniques. The structure and composition of the CS/SA and CS–OREC/SA composite sponges were characterized by FE-SEM, FT-IR, XRD and EDX. The results showed that the polyelectrolyte with a highly cross-linked structure and uniform pore distribution could be obtained by mixing CS and SA with or without the addition of OREC into them. Besides, the low cytotoxicity and excellent antibacterial efficacy of the prepared CS/SA and CS–OREC/SA sponges were demonstrated by an MTT assay and an antibacterial assay. Moreover, the results of the hemostatic tests on ear-artery, ear-vein and liver injuries of rabbits showed that the addition of OREC into the CS/SA composite sponge significantly improved the hemostatic efficiency of the as-prepared sponge without compromising the biocompatibility and antibacterial property of CS. This study indicated that the CS–OREC/SA composite sponge had the potential to be a potent hemostat for controlling wound infection and bleeding in medical fields.

Xiaoxing Lv

Papers

Biomimetic LBL structured nanofibrous matrices assembled by chitosan/collagen for promoting wound healing

The status of microRNA-21 expression and its clinical significance in human cutaneous malignant melanoma.

Zeolite-based hemostat QuikClot releases calcium into blood and promotes blood coagulation in vitro.

Expression of MicroRNA-301a and its Functional Roles in Malignant Melanoma.

Antibacterial and hemostatic performance of chitosan–organic rectorite/alginate composite sponge