Molecular Engineering of Electrosprayed Hydrogel Microspheres to Achieve Synergistic Anti-Tumor Chemo-Immunotherapy with ACEA Cargo.

Molecular engineering of drug delivering platforms to provide collaborative biological effects with loaded drugs is of great medical significance. Herein, cannabinoid receptor 1 (CB1)- and reactive oxygen species (ROS)-targeting electrosprayed microspheres (MSs) are fabricated by loading with the CB1 agonist arachidonoyl 2'-chloroethylamide (ACEA) and producing ROS in a photoresponsive manner. The synergistic anti-tumor effects of ACEA and ROS released from the MSs are assessed. ACEA inhibits epidermal growth factor receptor signaling and altered tumor microenvironment (TME) by activating CB1 to induce tumor cell death. The MSs are composed of glycidyl methacrylate-conjugated xanthan gum (XGMA) and Fe3+, which form dual molecular networks based on a Fe3+-(COO-)3 network and a C═C addition reaction network. Interestingly, the Fe3+-(COO-)3 network can be disassembled instantly under the conditions of lactate sodium and ultraviolet exposure, and the disassembly is accompanied by massive ROS production, which directly injures tumor cells. Meanwhile, the transition of dual networks to a single network boosts the ACEA release. Together, the activities of the ACEA and MSs promote immunogenic tumor cell death and create a tumor-suppressive TME by increasing M1-like tumor-associated macrophages and CD8+ T cells. In summation, this study demonstrates strong prospects of improving anti-tumor effects of drug delivering platforms through molecular design.

The 50% and 95% effective dose of remimazolam tosilate for anaesthesia induction in sleep disorders patients undergoing laparoscopic cholecystectomy: an up-and-down sequential allocation trial.

PURPOSE: Previous reports argue that preoperative sleep conditions of patients can influence the dosage of general anaesthesia drugs. Therefore, we aimed to investigate the dose-effect relationship of preoperative sleep disorders on the induction of general anaesthesia with remimazolam tosilate and calculate the Median effective (ED50) and 95% effective (ED95) dosages. METHODS: Included in our study were 56 patients who underwent laparoscopic cholecystectomy at our hospital. A separate group of 27 patients with sleep disorders (SD group) and 29 patients without sleep disorders (NSD group) using the Pittsburgh Sleep Quality Index (PSQI) were also included. According to the Dixon 'up-and-down' design, patients received remimazolam at preselected concentrations starting at 0.2 mg/kg. After the administration of remimazolam, loss of consciousness was observed. By observing whether consciousness disappeared within a minute, we adjusted the dose of remimazolam by 0.1 mg/kg (up and down) in the following patient. The Median effective dose (ED50), 95% effective dose (ED95), and 95% confidence interval (CI) of remimazolam for effective sedation were calculated. RESULTS: The ED50 of remimazolam was 0.226 mg/kg (95%CI 0.221-0.232 mg/kg) in the SD group and 0.191 mg/kg (95%CI, 0.183-0.199 mg/kg) in the NSD group. The ED95 of remimazolam was 0.237 mg/kg (95%CI 0.231-0.262 mg/kg) in the SD group and 0.209 mg/kg (95%CI 0.200-0.254 mg/kg) in the NSD group. CONCLUSIONS: In the SD group, the ED50 and ED95 of remimazolam during anaesthesia induction were 0.226 and 0.237 mg/kg, respectively. The induction dose of remimazolam in the SD group was significantly higher than that in the NSD group.

Utilizing network pharmacological analysis to investigate the key targets and mechanisms of kaempferol against oxaliplatin-induced neurotoxicity.

This study investigated the pharmacological mechanism of kaempferol in the treatment of oxaliplatin-induced neuropathic pain by network pharmacological method and cells experiment. The kaempferol and disease target genes were obtained from several databases, including TCMSP, SwissTargetPrediction, GeneCards, and CTD. Then, the common target genes of drugs and diseases were obtained using Venny online tools. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional analyses were carried out to obtain the enriched molecular pathways associated with the kaempferol and disease. Finally, we constructed a neuropathic pain cell experiment to confirm the findings. 138 intersection targets were identified between targets of kaempferol and oxaliplatin-induced neurotoxicity. Enrichment analyses revealed that the IL-17 signaling pathway was associated with the therapeutic effects of kaempferol. Kaempferol down-regulated the mRNA expression levels of TNF-α, IL-6, and CCL2 in oxaliplatin-treated astrocytes. Our findings showed that kaempferol alleviated oxaliplatin-induced neurotoxicity via regulation of inflammation-related genes.

Relationship between Biodegradation Rate and Grain Size Itself Excluding Other Structural Factors Caused by Alloying Additions and Deformation Processing for Pure Mg.

This work studied the relationship between biodegradation rate and grain size itself, excluding other structural factors such as segregations, impure inclusions, second phase particles, sub-structures, internal stresses and textures caused by alloying additions and deformation processing for pure Mg. A spectrum of grain size was obtained by annealing through changing the annealing temperature. Grain boundary influenced the hardness and the biodegradation behavior. The hardness was grain size-dependent, following a typical Hall-Petch relation: HV=18.45+92.31d-12. The biodegradation rate decreased with decreasing grain size, following a similar Hall-Petch relation: Pi=0.17-0.68d-12 or Pw=1.34-6.17d-12. This work should be helpful for better controlling biodegradation performance of biodegradable Mg alloys through varying their grain size.

Cannabinoid Receptor-1 suppresses M2 macrophage polarization in colorectal cancer by downregulating EGFR.

Cannabinoid receptors, CB1 and CB2, have been implicated as emerging targets for cancer therapy. Herein, we investigated the potential regulation mechanism of CB1 and its implications in colorectal cancer. CB1 and EGFR expression were examined in colorectal cancer cell lines. The effects of CB1 agonist ACEA and its antagonist AM251 on the proliferation, migration and invasion of colorectal cancer cells and the expression of M1 and M2 macrophage markers were examined. EGFR overexpression was performed with plasmids containing EGFR gene. Tumor xenografts were constructed to explore the effects of CB1 activation on tumorigenesis. We showed that CB1 was downregulated while EGFR was upregulated in colorectal cancer cells. The activation of CB1 suppressed the proliferation, migration and invasion of colorectal cancer cells and the differentiation of M2 macrophages, while CB1 inhibition had opposite effects. Moreover, the alterations in tumorigenesis and M2 macrophage activation induced by CB1 activation were counteracted by EGFR overexpression. Besides, CB1 silencing promoted tumor cell proliferation and M2 polarization which was counteracted by EGFR knockdown. In vivo, CB1 activation also repressed tumorigenesis and M2 macrophage activation. The present study demonstrated that CB1 activation suppressed M2 macrophage through EGFR downregulation in colorectal cancers. These findings first unveiled the potential avenue of CB1 as a targeted therapy for colorectal cancer.

Substance P modulates BMSCs migration for tissue repair through NK-1R/CXCR4/p-Akt signal activation.

BACKGROUND: The migration of bone marrow-derived mesenchymal stem cells (BMSCs) to the wound site played an important role in tissue repair. Substance P (SP) has been studied and reported to be involved in tissue repair by promoting the growth of endothelial cells and the migration of BMSCs. However, the complicated process and the molecular mechanisms were not fully understood. Thus, we aimed to investigate the effect of SP-induced BMSCs migration on tissue repair and its possible mechanism. METHODS AND RESULTS: Western blot and q-PCR assay revealed that SP could induce the BMSCs migration through overexpression of CXCR4 and upregulation of Akt phosphorylation. And the upregulation was related to the activation of neurokinin-1 receptor (NK-1R). Besides, we found that the increased phosphorylation Akt caused by SP could be canceled by the inhibition of CXCR4 both in vitro and in vivo. Furthermore, a skin-injury animal model was established and used to observe the tissue repair process. Results showed that SP could accelerate wound closure, gain more granulation tissue accumulation, and more collagen deposition through the promotion of angiogenesis and induction of the BMSCs migration to the wound site. And these effects could be impaired by inhibition of CXCR4 and p-Akt. CONCLUSIONS: Our results suggested that SP promoted tissue repair through BMSCs migration via upregulation of CXCR4 and p-Akt. The expression of CXCR4 and p-Akt were regulated by NK-1R activation. These findings add more evidence in understanding the mechanisms of SP-induced BMSCs migration and highlight the potential for clinical implementation of SP in tissue repair.

Circular RNA CCDC66 Improves Murine Double Minute 4 (MDM4) Expression through Targeting miR-370 in Colorectal Cancer.

INTRODUCTION: Colorectal cancer (CRC), a common digestive tract tumor that contains colon and rectal cancer, is one of the three most common cancers globally. circRNAs are involved in the occurrence and development of CRC, but the mechanism of how they participate in this process remains unclear. METHODS: We adopted PCR for expression measure, CCK-8 for cell proliferation detection, Transwell for cell migration and invasion detection, and dual-luciferase reporter assays to detect the potential downstream targets of CCDC66 in CRC. RESULTS: This study showed that circRNA CCDC66 was overexpressed in CRC tissues, and after knockdown, it inhibited the proliferation, migration, and invasion of CRC cells (RKO and HCT-116) in vitro. In addition, the dual-luciferase reporter assay showed that there was a binding site between circCCDC66 and miR-370, as well as between miR-370 and murine double minute 4 (MDM4). That is, circCCDC66 upregulated the expression of MDM4 through competitively binding to miR-370. The expression of circCCDC66 in CRC tissues was positively correlated with MDM4 and negatively correlated with miR-370. CONCLUSION: In summary, our results indicate that circCCDC66 is a key upregulation of CRC. circCCDC66 upregulates MDM4 through competitive binding to miR-370, thereby enhancing the metastatic ability of CRC cells and promoting the development of CRC.

Ischemic preconditioning-induced protective effect for promoting angiogenesis in renal ischemia-reperfusion injury by regulating miR-376c-3p/HIF-1α/VEGF axis in male rats.

OBJECTIVE: Ischemic preconditioning (IPC) is defined as a well-established phenomenon in which brief exposure to sublethal episodes of ischemia and reperfusion induces a tolerance to injurious effects of prolonged ischemia by exploiting intrinsic defence mechanisms. The present study was performed to determine the protective effect of IPC on the rat renal ischemia-reperfusion injury (IRI) via miR-376c-3p/HIF-1α/VEGF axis. METHODS: In vivo, these male Sprague-Dawley rats were treated by IRI and IPC. Meanwhile, these rats from different treatment groups were also injected subcutaneously with 2 nmol agomir-376c-3p and/or 10 nmol recombinant rat HIF-1α. At 72 h after reperfusion, serum samples were respectively collected for renal function. Besides, kidney tissues were harvested to observe renal morphology changes. Subsequently, the expression levels of CD31, HIF-1α and VEGF in the kidney tissues were measured using immunohistochemical staining, quantitative real-time PCR, as well as Western blotting analysis at the indicated time points after reperfusion. In vitro, HK-2 cells were used to detect the cell activity by CCK-8 and transfection of mir-376c-3p mimic in Hypoxia/Reoxygenation (H/R) group. RESULTS: In vivo, the pathological changes were significantly relieved in the rats with IPC group, compared to the IRI group. Rats which were treated IPC significantly reduced the levels of blood urea nitrogen (BUN), serum creatinine (Scr) at 24 h after operation, compared to IRI group. After IPC treatment, the expression level of CD31 was obviously decreased, compared to IRI group. A total of differently expressed microRNAs were screened out by microRNA microarray assay in rat renal ischemia tissue, especially showing that miR-376c-3p was selected as the target miRNA. Compared to IRI group, the expression level of miR-376c-3p were obviously higher in IPC-treated group. Double-luciferase reporter assay demonstrated that miR-376c-3p directly targeted HIF-1α. In vitro, IPC significantly increased cell viability of HK-2, and promoted the angiogenesis via up-regulating miR-376c-3p/HIF-1α/VEGF axis. Furthermore, the expression level of HIF-1α was apparently decreased in HK-2 treated with H/R after miR-376c-3p mimic transfection respectively, as well as the increased expression level of VEGF. CONCLUSIONS: Our study provided a novel insight for investigating the protective effect of IPC on renal IRI. Consequently, miR-376c-3p played an important role in renal IRI by promoting angiogenesis via targeting HIF-1α/VEGF pathway in male rats.

miR-511-5p Suppresses Cell Migration, Invasion and Epithelial-Mesenchymal Transition Through Targeting PAK2 in Gastric Cancer.

As a malignant tumor, gastric cancer (GC) is closely related with gastric mucosa and has a high mortality in the world. Since microRNA (miRNA) has become more and more important in tumor research, we intend to find out the functional role and mechanism of miR-511-5p in GC. Firstly, miR-511-5p level was examined in human GC cell lines and tissues, and its effect on cell migration and invasion of BGC-823 or HGC-27 cells was tested by migration assay and transwell assay. Then, we confirmed the association between miR-511-5p and p21 activated kinase 2 (PAK2) by the luciferase reporter assay, and further assessed their role in cell migration and invasion. Moreover, we verified the function of miR-511-5p and PAK2 in epithelial-mesenchymal transition (EMT). In our study, miR-511-5p was downregulated in GC cell lines and tissues, and inversely associated with PAK2. Luciferase reporter assay confirmed that miR-511-5p could bind to PAK2. MiR-511-5p mimics significantly upregulated E-cadherin and downregulated N-cadherin, Vimentin and Snail, and consequently inhibited cell migration and invasion. However, reintroduction of PAK2 reversed the inhibitory function of miR-511-5p on BGC-823 and HGC-27 cells. Our research suggested that tumor-suppressive function of miR-511-5p in GC was inhibited by PAK2, and miR-511-5p/PAK2 axis may serve as a new strategy in GC management.

In vitro and in vivo human gastric cancer inhibition by Trifolirhizin is facilitated via autophagy, mitochondrial mediated programmed cell death, G2/M phase cell cycle arrest and inhibition of m-TOR/PI3K/AKT signalling pathway.

Retraction of: 'In vitro and in vivo human gastric cancer inhibition by Trifolirhizin is facilitated via autophagy, mitochondrial mediated programmed cell death, G2/M phase cell cycle arrest and inhibition of m-TOR/PI3K/AKT signalling pathway', by Ke Zhang, Weidong Liu*, Zhan Qu, Qin Liu, Jie Chen, Ran Tao, Youming Deng, Yu Zhang JBUON 2019;24(3):1100-1105; PMID:31424667. Following the publication of the above article, readers drew to our attention that part of the data was unreliable. The authors were requested to provide the raw data to prove the originality, but were unable to do so. After an investigation, the Editors of JBUON decided to retract this article. We thank the readers for bringing this matter to our attention. We apologize for any inconvenience it may cause.

Efficacy and safety of paravertebral block versus intercostal nerve block in thoracic surgery and breast surgery: A systematic review and meta-analysis.

OBJECTIVE: To evaluate the analgesic efficacy and safety of paravertebral block (PVB) versus intercostal nerve block (INB) in thoracic surgery and breast surgery. METHODS: The PubMed, Web of Science, Embase and the Cochrane Library were searched up to February 2020 for all available randomized controlled trials (RCTs) that evaluated the analgesic efficacy and safety of PVB compared with INB after thoracic surgery and breast surgery. For binary variables, odds ratio (OR) and 95% confidence interval (CI) was used. For continuous variables, weighted mean difference (WMD) and 95% confidence interval (CI) were used. RevMan5. 3 and Stata/MP 14.0 were used for performing the meta-analysis. RESULTS: A total of 9 trials including 440 patients (PVB block:222 patients; INB: 218 patients) met the inclusion criteria. In the primary outcome, there was no significant differences between the two groups with respect to postoperative visual analogue scale (VAS) at 1h (Std. MD = -0. 20; 95% CI = -1. 11to 0. 71; P = 0. 66), 2h (Std. MD = -0. 71; 95% CI = -2. 32to 0. 91; P = 0. 39), 24h (Std. MD = -0. 36; 95% CI = -0. 73 to -0. 00; P = 0. 05) and 48h (Std. MD = -0. 04; 95% CI = -0. 20 to 0. 11; P = 0. 57). However, there was significant difference in VAS of non Chinese subgroup at 1h (Std. MD = 0. 33; 95% CI = 0. 25to 0. 41; P<0. 00001) and VAS of Chinese subgroup at 24h (Std. MD = -0.32; 95% CI = -0.49 to-0.14; P = 0.0003). In the secondary outcome, the analysis also showed no significant difference between the groups according to the rates of postoperative nausea and vomit (OR = 0. 63; 95% CI = 0. 38 to 1. 03; P = 0. 06) and the rates of postoperative additional analgesia (OR = 0. 57; 95% CI = 0. 21 to 1. 55; P = 0. 27). There was significant difference in postoperative consumption of morphine (Std. MD = -14. 57; 95% CI = -26. 63 to -0.25; P = 0. 02). CONCLUSION: Compared with INB, PVB can provide better analgesia efficacy and cause lower consumption of morphine after thoracic surgery and breast surgery.

Clinical characteristics and predictors of permanent stoma in rectal cancer patients underwent anterior resections: the value of preoperative prognostic nutritional index.

OBJECTIVES: This study was aimed to investigate the correlation between preoperative prognostic nutritional index (PNI) and permanent stoma (PS) in patients with defunctioning stoma (DS) after anterior resections and, based on it, to reveal the clinical value of PNI on clinical strategies about the selection of stoma location. METHODS: A total of 281 consecutive rectal cancer patients who accepted anterior resection and DS in the National Hepatobiliary and Enteric Surgery Research Center, Xiangya Hospital, Central South University from June 2008 to June 2018 were enrolled in this study. Receiver operating characteristic (ROC) curve for PNI was performed to discriminate PS. Univariate and multivariate analysis were conducted to identify the clinical characteristics and risk factors for PS. Specific reasons for patients with DS turned into PS were reviewed. RESULTS: ROC curve analysis defined PNI cutoff level of 45.85 corresponding to PS (area under the curve (AUC) = 0.71, 77% sensitivity, 56.9% specificity). Low PNI (OR = 3.23, P = 0.005), tumor crossing the peritoneal reflection (PR) (OR = 3.42, P = 0.003), postoperative distant metastasis (OR = 6.31, P < 0.001) were independently associated with PS. Besides, anastomotic complications (31.4%), poor oncological outcomes (35.3%), and personal preferences (33.3%) were the specific reasons for patients turning into PS. CONCLUSIONS: Preoperative PNI is an independent prognostic factor to predict PS in patients who underwent anterior resection and DS. Therefore, combined with other clinical characteristics and predictors, preoperative measurements of PNI could provide a significant support for clinical decision on patients prepared to accept anterior resection and DS.

Niacin Metal-Organic Framework-Laden Self-Healing Hydrogel for Wound Healing.

Bacterial infection is one of the most significant impediments to wound healing. To treat wounds, non-biological and non-pharmacological interventions have gained increasing importance as they are easily translatable into clinical products. In this study, we developed a niacin metal-organic frameworks (NOFs)-laden hybrid hydrogel with self-healing ability for better wound healing. The copper based-NOFs (Cu-NOFs) and zinc based-NOFs (Zn-NOFs) were constructed and encapsulated into the self-healing hydrogels, which could prevent NOFs from directly interacting with protein-containing solutions (e. g., tissue fluid). The hydrogel was prepared by using four-armed benzaldehyde-terminated polyethylene glycol (BAPEG) and carboxymethyl chitosan (CMC). Our results showed that the hydrogel gained self-healing ability through reversible Schiff base reaction. In addition, after loading NOFs, the hybrid hydrogel exerted significant effects on antibacterial and antioxidant activities. The in vivo studies demonstrated that the hybrid hydrogel could alleviate inflammation and enhance the formation of granulation tissue, collagen and vascular tissue, thereby promoting wound closure in rats with E. coli -infected wounds. Overall, this study highlights the tremendous potential for the clinical implementation of NOFs-laden hydrogel with good self-healing, antibacterial and antioxidant properties in wound healing.

In vitro and in vivo human gastric cancer inhibition by Trifolirhizin is facilitated via autophagy, mitochondrial mediated programmed cell death, G2/M phase cell cycle arrest and inhibition of m-TOR/PI3K/AKT signalling pathway.

PURPOSE: To investigate the anticancer effects of Trifolirhizin in SNU-5 human gastric cancer cells along with evaluation of its effects on autophagy, apoptosis, cell cycle phase distribution and m-TOR/PI3K signalling pathway. METHODS: The antiproliferative effect on gastric cancer cells was assessed by MTT assay. Autophagy was detected by electron microscopy and western blot. Apoptotic cell death was revealed by acridine orange (AO)/ethidium bromide (EB) and annexin V/propidium iodide (PI) staining using flow cytometry. Cell cycle analysis was carried out by flow cytometry. Protein expression was determined by immunoblotting. Xenografted mice models were used to evaluate in vivo the anticancer effects of Trifolirhizin. RESULTS: Trifolirhizin could significantly inhibit the proliferation of the gastric cancer cells. The anticancer activity of Trifolirhizin against the gastric cancer cells was found to be due to induction of autophagy and mitochondrial-mediated apoptosis. It was further observed that both apoptosis and autophagy-related protein expressions sere significantly altered. Further, it was found that Trifolirhizin could inhibit the m-TOR/PI3K/AKT signalling pathway. In vivo evaluation in xenografted mice indicated that Trifolirhizin inhibited significantly both tumor weight and tumor volume. CONCLUSIONS: In conclusion, it can be safely stated that Trifolirhizin has the potential to be developed as a potent anticancer agent against gastric carcinoma provided further in depth evaluation of this compound is performed.

Novel in situ forming hydrogel based on xanthan and chitosan re-gelifying in liquids for local drug delivery.

Injectable hydrogels have been an attractive topic in biomaterials. However, during gelation in vivo, they are easy to disperse due to tissue exudates, thus leading to failure of controlled drug release. To solve this problem, we present a novel polysaccharide-based injectable hydrogel via self-crosslinking of aldehyde-modified xanthan (Xan-CHO) and carboxymethyl-modified chitosan (NOCC). The physical properties were optimized by adjusting the mass ratio of Xan-CHO and NOCC. Experiments revealed that this material exhibited the characteristics of self-healing, anti-enzymatic hydrolysis, biocompatibility and biodegradability. The releasing curve demonstrated stable release of BSA-FITC within 10 h after injection in liquids. After incorporation with a vascular endothelial growth factor, there was an interaction between this biomaterial and the host, which accelerated the reconstruction of the abdominal wall in rats. Therefore, this injectable hydrogel, as a drug delivery system, can prevent drug outburst in a variety of settings and function as a tissue scaffold.

Phf8 histone demethylase deficiency causes cognitive impairments through the mTOR pathway.

Epigenomic abnormalities caused by genetic mutation in epigenetic regulators can result in neurodevelopmental disorders, deficiency in neural plasticity and mental retardation. As a histone demethylase, plant homeodomain finger protein 8 (Phf8) is a candidate gene for syndromal and non-specific forms of X-chromosome-linked intellectual disability (XLID). Here we report that Phf8 knockout mice displayed impaired learning and memory, and impaired hippocampal long-term potentiation (LTP) without gross morphological defects. We also show that mTOR signaling pathway is hyperactive in hippocampus in Phf8 knockout mouse. Mechanistically, we show that demethylation of H4K20me1 by Phf8 results in transcriptional suppression of RSK1 and homeostasis of mTOR signaling. Pharmacological suppression of mTOR signaling with rapamycin in Phf8 knockout mice recovers the weakened LTP and cognitive deficits. Together, our results indicate that loss of Phf8 in animals causes deficient learning and memory by epigenetic disruption of mTOR signaling, and provides a potential therapeutic drug target to treat XLID.

Systemic blockade of P2X7 receptor protects against sepsis-induced intestinal barrier disruption.

Sepsis, during which the intestinal epithelial barrier is frequently disrupted, remains a challenging and life-threatening problem in clinical practice. The P2X7 receptor (P2X7R) is a non-selective adenosine triphosphate-gated cation channel present in macrophages that is involved in inflammatory responses. However, little is known about the role of P2X7R in macrophages during sepsis-induced intestinal barrier disruption. In this study, mice were treated with the P2X7R antagonist A740003 or the agonist BzATP by intra-peritoneal injection after the induction of gut-origin sepsis. The survival rates, inflammatory responses, intestinal barrier integrity, macrophage marker expression, and ERK and NF-κB activities were evaluated. Intestinal macrophages were also isolated and studied after exposure to Brilliant Blue G or BzATP. We found that a systemic P2X7R blockade downregulated sepsis-induced inflammatory responses and attenuated intestinal barrier dysfunction based on the evidence that mice in the A740003-treated group exhibited alleviated pro-inflammatory cytokine synthesis, intestinal hyperpermeability, epithelial apoptosis rates and tight junction damage compared with the septic mice. These changes were partly mediated by the inhibition of M1 macrophages activation via ERK/NF-κB pathways. Our data presented herein show that a P2X7R blockade could be a potential therapeutic target for the treatment of sepsis-induced intestinal barrier dysfunction.

Injectable in situ cross-linking chitosan-hyaluronic acid based hydrogels for abdominal tissue regeneration.

Abdominal wall defect caused by open abdomen (OA) or abdominal trauma is a serious issue since it induces several clinical problems. Although a variety of prosthetic materials are commonly employed, complications occur including host soft tissue response, fistula formation and chronic patient discomfort. Recently, abundant natural polymers have been used for injectable hydrogel synthesis in tissue regeneration. In this study, we produced the chitosan - hyaluronic acid (CS/HA) hydrogel and investigated its effects on abdominal tissue regeneration. The physical and biological properties of the hydrogel were demonstrated to be suitable for application in abdominal wounds. In a rat model simulating open abdomen and large abdominal wall defect, rapid cellular response, sufficient ECM deposition and marked neovascularization were found after the application of the hydrogel, compared to the control group and fibrin gel group. Further, the possible mechanism of these findings was studied. Cytokines involved in angiogenesis and cellular response were increased and the skew toward M2 macrophages credited with the functions of anti-inflammation and tissue repair was showed in CS/HA hydrogel group. These findings suggested that CS/HA hydrogel could prevent the complications and was promising for abdominal tissue regeneration.

An Injectable, Wound-Adapting, Self-Healing Hydrogel for Fibroblast Growth Factor 2 Delivery System in Tissue Repair Applications.

Rapid wound healing is a fundamental health concern and poses a critical challenge for healthcare systems worldwide. Here, we developed an injectable, dynamic, self-healing hydrogel serving as a fibroblast growth factor 2 (FGF2) delivery system for tissue repair applications. Benzaldehyde-terminated polyethylene glycol (BAPEG) was synthesized and cross-linked with N-Succinyl-chitosan (SCS) through reversible Schiff-base reaction to form a dynamic self-healing hydrogel. Because it can be injected after gelation and self-heal into an integral part, the hydrogel could not only auto-adapt to the irregular wound surface to provide better protection but also encapsulate drugs homogeneously and implant into tissue with a less invasive strategy. As a result, the FGF2-loaded SCS/BAPEG hydrogel is able to significantly promote the process of angiogenesis, collagen deposition, and granulation tissue formation, as well as reduce inflammation. This study opens the door to self-healing hydrogels serving as a drug delivery system for tissue repair applications.

Tannin-based adhesive for protection of colonic anastomosis in the open abdomen.

This study was aimed to evaluate the effect of tannin acid- polyethylene glycol (TP) adhesive on the wound healing process of primary colonic anastomosis in the open abdomen (OA). Adhesion strength test, degradation and hemostatic ability of TP were investigated. In a rat model, after standard colonic anastomoses, rats were divided into three groups: OA group; OA + FG (fibrin glue) group; OA + TP group. Five days after surgery, body weight, anastomotic bursting pressure (ABP), and histology of anastomotic tissue were evaluated. Performance of adhesion strength and hemostatic ability of TP was better than that of FG. The weight of TP decreased by over 50% after 11-day incubation. All rats survived well after surgery. Compared to OA group and OA + FG group, OA + TP group showed a significant improvement in body weight, ABP and healing state. Application of TP adhesive, used as an auxiliary treatment of colonic anastomosis operation, improved the wound strength and promoted the anastomotic healing after OA.