Preparation and characterization of double macromolecular network (DMMN) hydrogels based on hyaluronan and high molecular weight poly(ethylene glycol)

Abundant research efforts have been devoted to meet the demands for high-strength hydrogels in biomedical applications. Double-network (DN) hydrogels and homogeneous hydrogels are two typical samples. In this study, a novel ultra-strong and resilient double macromolecular network (DMMN) hydrogel system has been developed via a two-step sequential cross-linking process using hyaluronan (HA) and high molecular weight poly(ethylene glycol) (PEG) for the first and second network, respectively. A lower concentration of the HA precursor solution and a higher concentration of the PEG precursor solution as well as a higher molecular weight of the PEG precursor are beneficial to produce high-strength DMMN gels. Dynamic light scattering measurements demonstrate that DMMN gels possess the more evenly distributed polymer networks; the distinctive double and relatively evenly distributed networks of the DMMN gel make it combine the current DN and homogeneous network strategies for preparing robust hydrogels. The optimized DMMN gel is capable of sustaining up to 50 MPa of compressive stress. Besides, DMMN gels exhibit excellent cytocompatibility. This study expands the DN principle in designing and fabricating high-strength hydrogels with biocompatible macromolecules that show a promising prospect for biomedical applications.Published versio

Enzymatically cross-linked hyaluronic acid/graphene oxide nanocomposite hydrogel with pH-responsive release

<div><p>Hyaluronic acid (HA) is made up of repeating disaccharide units (<i>β</i>-1,4-d-glucuronic acid and <i>β</i>-1,3-N-acetyl-d-glucosamine) and is a major constituent of the extracellular matrix. HA and its derivatives which possess excellent biocompatibility and physiochemical properties have been studied in drug delivery and tissue engineering applications. Tyramine-based HA hydrogel with good compatibility to cell and tissue has been reported recently. However, inferior mechanical property may limit the biomedical application of the HA hydrogel. In this study, HA/graphene oxide (GO) nanocomposite (NC) hydrogel was prepared through a horseradish peroxidase catalyzed <i>in situ</i> cross-linking process. As compared with pure HA hydrogels, incorporation of GO to the HA matrix could significantly enhance the mechanical properties (storage moduli 1800 Pa) of the hydrogel and prolong the release of rhodamine B (RB) as the model drug from the hydrogel (33 h) as well. In addition, due to the multiple interactions between GO and RB, the NC hydrogels showed excellent pH-responsive release behavior. The release of RB from the NC hydrogel was prolonged at low pH (pH 4.0) in the presence of GO, which could be attributed to the enhanced interactions between GO and HA as well as with RB. <i>In situ</i> three-dimensional encapsulation of mouse embryonic fibroblasts (BALB 3T3 cells) in the NC hydrogels and cytotoxicity results indicated the cytocompatibility of both the enzymatic cross-linking process and HA/GO NC hydrogels (cell viability 90.6 ± 4.25%). The enzymatically catalyzed fabrication of NC hydrogels proved to be an easy and mild approach, and had great potential in the construction of both tissue engineering scaffolds and stimuli-responsive drug release matrices.</p></div

β-Arrestin2 promotes docetaxel resistance of castration-resistant prostate cancer via promoting hnRNP A1-mediated PKM2 alternative splicing

Abstract Purpose To investigate the influence of β-arrestin2 on the docetaxel resistance in castration-resistant prostate cancer (CRPC) and elucidate the underlying molecular mechanisms. Methods PC3 and DU145 cells with stable β-arrestin2 overexpression and C4-2 cells with stable β-arrestin2 knockdown, were constructed via using lentivirus and puromycin selection. MTT and colony formation assays were carried out to investigate the effect of β-arrestin2 expression on the docetaxel resistance of CRPC cells. Glycolysis analysis was used to assess the glycolytic capacity modulated by β-arrestin2. GO enrichment analysis, gene set enrichment analysis and Spearman correlation test were carried out to explore the potential biological function and mechanism via using public data from GEO and TCGA. The expressions of PKM2, Phospho-PKM2, Phospho-ERK1/2 and hnRNP A1 were detected by western blot. Functional blocking experiments were carried out to confirm the roles of PKM2 and hnRNP A1 in the regulation of β-arrestin2’s biological functions via silencing PKM2 or hnRNP A1 expression in cells with stable β-arrestin2 overexpression. Finally, nude mice xenograft models were established to confirm the experimental results of cell experiments. Results β-Arrestin2 significantly decreased the sensitivity of CRPC cells to docetaxel stimulation, through enhancing the phosphorylation and expression of PKM2. Additionally, β-arrestin2 increased PKM2 phosphorylation via the ERK1/2 signaling pathway and induced PKM2 expression in a post-transcriptional manner through an hnRNP A1-dependent PKM alternative splicing mechanism, rather than by inhibiting its ubiquitination degradation. Conclusion Our findings indicate that the β-arrestin2/hnRNP A1/PKM2 pathway could be a promising target for treating docetaxel-resistant CRPC

[Scutellaria sp.]

原著和名: タツナミサウの類科名: シソ科 = Labiatae採集地: 岐阜県 多治見市 三ノ倉 (美濃 多治見市 三ノ倉)採集日: 1973/6/17採集者: 萩庭丈壽整理番号: JH018264国立科学博物館整理番号: TNS-VS-968264備考: DB作成協力会による補足あ

Transvaginal natural orifice endoscopic surgery for ovarian cystectomy: a more suitable surgical approach for the day-care procedure

IntroductionAlthough previous studies have shown that vaginal natural orifice transluminal endoscopic surgery (vNOTES) has the advantages of causing less pain, faster recovery, and better concealment of surgical incisions, which aligns with the concept of the day-care procedure, this approach poses a greater risk of damaging adjacent organs (i. e., rectum and bladder) due to its anatomical specificity. Moreover, the day-care procedure may lead to relatively less preoperative evaluation and postoperative care. Hence, it is necessary to explore the safety and effectiveness of vNOTES for ovarian cystectomy in the day-care procedure, to provide a theoretical basis for the wider development of vNOTES surgery.Materials and methodsThis retrospective study included 131 patients at our hospital who underwent ovarian cystectomy from September 2021 to October 2022. Based on the surgical approach, patients were classified into transumbilical laparoendoscopic single-site surgery (LESS) and vNOTES groups. The patients' demographic characteristics and follow-up data were collected during the perioperative period and 1-month postoperatively.ResultsVaginal natural orifice transluminal endoscopic surgery has less postoperative exhaust time, a lower postoperative 6-hour pain score, and a lower incidence of analgesic drug use, with higher surgical conversion incidence. Multiple linear regression analysis showed that the surgical conversion, chocolate cyst, bilateral cyst, and pelvic adhesion increased the operation duration by ~43 (95% CI: 10.309, 68.152, p &lt; 0.001), 15 (95% CI: 6.342, 45.961, p = 0.036), 10 (95% CI: 3.07, 40.166, p = 0.019), and 8 (95% CI: 4.555, 26.779, p = 0.035) min, respectively. Interestingly, vNOTES decreased the operation duration by ~8.5 min (95% CI: −18.313, −2.699, p = 0.033).ConclusionVaginal natural orifice transluminal endoscopic surgery was equally safe and effective for ovarian cystectomy compared to LESS. vNOTES aligned with the concept of the day-care procedure due to its reduced postoperative pain, shorter exhaust time, and absence of scarring. However, surgeons should conduct a comprehensive preoperative evaluation and exclude patients suspected to have severe pelvic adhesions