Preparation of healing promotive alanyl-glutamine-poly(p-dioxanone) electrospun membrane integrated with gentamycin and its application for intestinal anastomosis in rats.

Anastomosis surgery at the intestinal site is performed on millions of individuals every year. However, several persistent complications, such as anastomotic leakage, abnormal adhesion, and anastomotic stenosis, have been observed after the surgery. For promoting anastomotic healing and to overcome the challenges mentioned above, re-epithelialization at anastomotic sites is crucial. In this study, an epithelialization-promoting macromolecular prodrug Ala-Gln-PPDO was prepared and processed into fibrous membranes by electrospinning. Ala-Gln and gentamicin were sustainably released from the electrospun membranes with degradation of these membranes to promote the proliferation of rat intestinal epithelial cells and suppress the proliferation of Staphylococcus aureus and Escherichia coli. The comprehensive repair effects of Ala-Gln-PPDO membranes have been evaluated in rat models of intestinal anastomosis in this study. Application of Ala-Gln-PPDO membranes, especially the gentamicin-incorporated Ala-Gln-PPDO ones, could prevent adhesion between the injured intestine and surrounding intestinal tissues. In addition, they did not affect the healing strength of anastomotic stoma negatively and could promote re-epithelialization at the anastomotic sites. Furthermore, the gentamicin-incorporated Ala-Gln-PPDO membranes could relieve stenosis at anastomotic sites. The gentamicin-incorporated Ala-Gln-PPDO electrospun membrane is a promising, comprehensive implantable material for promoting healing after gastrointestinal anastomosis owing to its effects involving the promotion of re-epithelialization, prevention of adhesion, and relieving of anastomotic stenosis.

CircRNA VPRBP inhibits tumorigenicity of cervical cancer via miR-93-5p/FRMD6 axis.

BACKGROUND: Cervical cancer is a malignant tumor that threatens the life and health of women. Circular RNA (circRNA) is a research hotspot in human diseases including cervical cancer. However, the research of circRNA viral protein R-binding protein (circ_VPRBP) in cervical cancer is blank. METHODS: Real-time quantitative polymerase chain reaction (RT-qPCR) was used to detect the expression of target genes in cervical cancer tissues and cells. The expression of related proteins was detected by western blot. The localization of circ_VPRBP was detected by nuclear cytoplasmic separation, and the stability of circ_VPRBP was verified by actinomycin D. After transfection with oligonucleotides and/or plasmids, cell proliferation, migration, invasion and apoptosis were detected by 3-(4, 5-dimethylthiazol-2-yl) -2, 5-diphenyl-2-H-tetrazolium bromide (MTT), colony formation, 5-ethynyl-2'-deoxyuridine (EdU), transwell, or flow cytometry assays. Mechanistically, the interaction between microRNA-93-5p (miR-93-5p) and circ_VPRBP/FERM domain containing 6 (FRMD6) was verified by dual luciferase reporter assay. Animal experiment was conducted to investigate the role of circ_VPRBP in vivo. RESULTS: Circ_VPRBP was down-regulated in cervical cancer tissues and cells, and overexpression of circ_VPRBP inhibited proliferation and promoted apoptosis of Caski and C33A cells. MiR-93-5p was a target of circ_VPRBP, and miR-93-5p mimic reversed the effect of circ_VPRBP on cell behavior. FRMD6 was a downstream target of miR-93-5p, and down-regulated FRMD6 reversed the cell viability, migration and invasion of cervical cancer cells inhibited by anti-miR-93-5p. Circ_VPRBP inhibited tumor growth by regulating miR-93-5p and FRMD6 in vivo. CONCLUSION: Circ_VPRBP inhibited cell proliferation, migration and invasion and promoted cell apoptosis of cervical cancer cells by regulating miR-93-5p/FRMD6 axis.

Preparation of Fibroblast Suppressive Poly(ethylene glycol)-b-poly(l-phenylalanine)/Poly(ethylene glycol) Hydrogel and Its Application in Intrauterine Fibrosis Prevention.

Intrauterine adhesions (IUA) often occur as a result of trauma to the basal layer after curettage, postpartum hemorrhage, or surgical miscarriage. Endometrial fibrosis is the primary pathological feature of IUA. The characteristic features of IUA include excessive deposition and reorganization of the extracellular matrix, replacing the normal endometrium. To prevent uterine fibrosis after injury, we prepared and evaluated a type of fibroblast suppressive hydrogel. Poly(ethylene glycol)-b-poly(l-phenylalanine) (PEBP) copolymers were successfully synthesized by ring opening polymerization of l-Phenylalanine N-carboxyanhydride, initiated by methoxy-poly(ethylene glycol)-amine. Injectable PEBP/PEG hydrogels were subsequently formed through π-π accumulations between PEBP macromolecules and hydrogen bonds among PEBP, PEG, and H2O molecules. PEBP/PEG hydrogel could suppress the proliferation of fibroblasts due to the action of l-Phe, released sustainably from PEBP/PEG gels. Lastly, the in vivo preventive effect of PEBP/PEG hydrogel on fibrosis was evaluated in a rat uterine curettage model. It was found that PEBP/PEG hydrogel suppressed uterine fibrosis caused by curettage and promoted embryo implantation in injured uterine by regulating the expression and interactions of transforming growth factor beta 1 (TGF-ß1) and Muc-4. PEBP/PEG hydrogels have the potential for application in uterine adhesion prevention owing to their fibrosis preventive and pregnancy promotiing effects on uterine tissue after injury.

Anti-Adhesive, Platelet Gathering Effects of c-RGD Modified Poly(p-dioxanone-co-l-Phe) Electrospun Membrane and Its Comprehensive Application in Intestinal Anastomosis.

Intestinal resection and anastomosis are performed in over a million people with various bowel diseases annually. Excessive fibrosis and anastomotic site leakage are the main complications of anastomosis surgery, despite great improvements in operative technique and equipment in recent years. In this study, cRGD modified poly(p-dioxanone-co-l-Phe) (PDPA) membranes are designed and applied in intestinal anastomosis to simultaneously solve the two aforementioned complications. cRGD is modified onto PDPA membranes through both physical absorption and π-π accumulation between d-Phe of cRGD and l-Phe of PDPA. Although cRGD modification enhanced the biocompatibility of PDPA membranes, cRGD modified PDPA membrane suppresses fibroblast proliferation both in vitro and in vivo as a result of degradation and subsequent release of fibroblast suppressive l-Phe from PDPA. Meanwhile, platelets are entrapped by cRGD modified PDPA membranes through the specific binding of cRGD and platelet GPIIbIIIa . cRGD modified PDPA membranes are applied in rat intestinal anastomosis, and both adhesion and stenosis are successfully prevented at anastomotic sites. At the same time, bursting pressure, which represents healing intensity at anastomotic sites, is promoted. The gathering and activation of platelets on PDPA membranes induce secretion of autologous PDGF and VEGF to facilitate angiogenesis and subsequent healing of anastomotic sites.