Hybrid Double-Sided Tape with Asymmetrical Adhesion and Burst Pressure Tolerance for Abdominal Injury Treatment.

Patients with open abdominal (OA) wounds have a mortality risk of up to 30%, and the resulting disabilities would have profound effects on patients. Here, we present a novel double-sided adhesive tape developed for the management of OA wounds. The tape features an asymmetrical structure and employs an acellular dermal matrix (ADM) with asymmetric wettability as a scaffold. It is constructed by integrating a tissue-adhesive hydrogel composed of polydopamine (pDA), quaternary ammonium chitosan (QCS), and acrylic acid cross-linking onto the bottom side of the ADM. Following surface modification with pDA, the ADM would exhibit characteristics resistant to bacterial adhesion. Furthermore, the presence of a developed hydrogel ensures that the tape not only possesses tissue adhesiveness and noninvasive peelability but also effectively mitigates damage caused by oxidative stress. Besides, the ADM inherits the strength of the skin, imparting high burst pressure tolerance to the tape. Based on these remarkable attributes, we demonstrate that this double-sided (D-S) tape facilitates the repair of OA wounds, mitigates damage to exposed intestinal tubes, and reduces the risk of intestinal fistulae and complications. Additionally, the D-S tape is equally applicable to treating other abdominal injuries, such as gastric perforations. It effectively seals the perforation, promotes injury repair, and prevents the formation of postoperative adhesions. These notable features indicate that the presented double-sided tape holds significant potential value in the biomedical field.

Inhibition of chemokine receptor CXCR2 attenuates postoperative peritoneal adhesion formation.

BACKGROUND: Postoperative peritoneal adhesions remain a problem after general and gynecological surgery. METHODS: Hematoxylin and eosin and Masson's trichrome staining of ischemic buttons were performed 6, 12, 24 hours, and 7 days after button induction. Scanning electron microscopy, ribonucleic acid sequencing, quantitative real-time polymerase chain reaction, immunohistochemical staining, and flow cytometry were used to elucidate the pathophysiology of postoperative peritoneal adhesions. RESULTS: The results showed that thickening of the peritoneum and abscission of mesothelial cells and collagen fibers increased significantly on the surface of the "button" in the control groups at 24 hours postoperatively. Scanning electron microscopy revealed a large number of granulocytes on the button surface in the control group at 24 hours. Ribonucleic acid sequencing and quantitative real-time polymerase chain reaction also revealed that CXCR2 expression was significantly upregulated. In addition, danirixin, a CXCR2 inhibitor, reduced abdominal adhesion in the injured area by inhibiting the infiltration of inflammatory cells and collagen production. Immunohistochemical staining showed decreased expression of CXCR2 in the adhesion area 7 days after surgery in the treatment group. Flow cytometry showed a significantly decreased neutrophil ratio in the treatment group compared with that in the control group 24 hours after the operation. CONCLUSIONS: Inflammation plays an important role in the early stages of postoperative peritoneal adhesion formation, whereas collagen fibers and angiogenesis play important roles in the late stages. The CXCL2-CXCL3-CXCR2 signaling axis is an important link in the mechanism of postoperative peritoneal adhesion formation, and the application of CXCR2 inhibitors can alleviate the formation of postoperative peritoneal adhesions.

Correction: Engineering an adhesive based on photosensitive polymer hydrogels and silver nanoparticles for wound healing.

Correction for 'Engineering an adhesive based on photosensitive polymer hydrogels and silver nanoparticles for wound healing' by Qinqing Tang et al., J. Mater. Chem. B, 2020, 8, 5756-5764, DOI: 10.1039/d0tb00726a.

Altered intestinal microflora and barrier injury in severe acute pancreatitis can be changed by zinc.

To investigate the effect of zinc (Zn) supplementation on intestinal microflora changes and bacterial translocation in rats with severe acute pancreatitis (SAP), the rats were divided into the sham surgery (SS), SAP, SS + Zn, and SAP + Zn groups. Saline (0.1 mL/100g) and 5% sodium taurocholate were injected into the pancreaticobiliary duct of the rats in the SS and SAP + Zn groups, respectively. Intraperitoneal injection of 5 mg/kg Zn was performed immediately after injecting saline or 5% sodium taurocholate into the rats in both groups. Serum amylase and Zn levels, plasma endogenous endotoxin, intestinal permeability, and the positive rate of intestinal bacterial translocation were detected, haematoxylin and eosin (H&E) staining was performed, and the pancreatic tissue scores were calculated for each group. In addition, immunohistochemical (IHC) staining was performed to evaluate the expression of IL-1ß and TNF-α. Real-time fluorescence quantitative PCR was used to quantify the gene copy numbers of Escherichia, Bifidobacterium, and Lactobacillus in the cecum. The levels of amylase and plasma endotoxin in the SAP group were significantly higher than those in the SS and SS + Zn groups. Intestinal mucosal permeability and intestinal bacterial translocation in the liver, pancreas, and mesenteric lymph nodes were increased in the SAP group. However, the levels of amylase and plasma endotoxin were decreased as a result of zinc supplementation in the SAP group. The expression of IL-1ß and TNF-α was also reduced to a greater degree in the SAP + Zn group than in the SAP group. Moreover, alleviated intestinal mucosal permeability and intestinal bacterial translocation in the liver, pancreas, and mesenteric lymph nodes were found in the SAP + Zn group. The results of real-time quantitative PCR showed that the gene copy number of Escherichia increased with time, and the gene copy numbers of Lactobacillus and Bifidobacterium decreased over time. Zn supplementation prevented the release of TNF-α and IL-1ß, alleviated intestinal permeability and endotoxemia, reduced bacterial translocation, and inhibited changes in pathogenic intestinal flora in rats with SAP.

Nutritional Management of Patients With Enterocutaneous Fistulas: Practice and Progression.

The management of enterocutaneous fistulas (ECF) can be challenging because of massive fluid loss, which can lead to electrolyte imbalance, severe dehydration, malnutrition and sepsis. Nutritional support plays a key role in the management and successful closure of ECF. The principle of nutritional support for patients with ECF should be giving enteral nutrition (EN) priority, supplemented by parenteral nutrition if necessary. Although total parenteral nutrition (TPN) may be indicated, use of enteral feeding should be advocated as early as possible if patients are tolerant to it, which can protect gut mucosal barrier and prevent bacterial translocation. A variety of methods of enteral nutrition have been developed such as fistuloclysis and relay perfusion. ECF can also be occluded by special devices and then EN can be implemented, including fibrin glue application, Over-The-Scope Clip placement and three-dimensional (3D)-printed patient-personalized fistula stent implantation. However, those above should not be conducted in acute fistulas, because tissues are edematous and perforation could easily occur.

Engineering an adhesive based on photosensitive polymer hydrogels and silver nanoparticles for wound healing.

Hemostasis, wound closure and prevention of infection are critical to wound healing after an injury. Skin adhesives have been used to seal incisions, thus aiding primary wound healing, as well as creating a barrier to microbes. We constructed a skin adhesive with antibacterial and hemostatic activities (AHAs) for wound management. The adhesive was made by using methacrylated hyaluronan-polyacrylamide (MHA-PAAm) hydrogels, integrated with silver nanoparticles (AgNPs) and bonded to gelatin. Because of the three-dimensional network structure of the hydrogels, nanoscale particles can be encapsulated into their voids; the AgNPs, through sustained delivery of silver ions, endow the adhesives with sustained broad-spectrum antibacterial activity. Furthermore, due to the introduction of MHA which can be crosslinked by visible light, the polyacrylamide hydrogel matrix can be formed through photo crosslinking. In addition, gelatin can be bonded to both the hydrogel matrix and host tissues because of the interaction between carboxyl and amino-moieties. Our animal studies demonstrated that the AHAs which possess tissue adhesive and antibacterial properties were easy to stretch, and were able to stop bleeding in rat tail amputation and liver injury models. AHAs enhance wound granulation tissue formation, vascular tissue formation, and collagen formation, as well as alleviate inflammation. These properties promoted wound closure in rat wound infection models, promising great potential for applying AHAs in clinical uses.

Mincle/Syk Signalling Promotes Intestinal Mucosal Inflammation Through Induction of Macrophage Pyroptosis in Crohn's Disease.

BACKGROUND: Macrophage-inducible C-type lectin [Mincle] signalling plays a proinflammatory role in different organs such as the brain and liver, but its role in intestinal inflammation, including Crohn's disease [CD], remains unknown. METHODS: The characteristics of Mincle signalling expression in CD patients and experimental colitis were examined. The functional role of Mincle signalling in the intestine was addressed in experimental colitis models in vivo by using Mincle knock-out [Mincle-/-] mice. In addition, neutralising anti-Mincle antibody, downstream spleen tyrosine kinase [Syk] inhibitor, and Mincle pharmacological agonist were used to study the Mincle signalling in intestine. Bone marrow-derived macrophages were collected from mice and used to further verify the effect of Mincle signalling in macrophages. RESULTS: This study has shown that Mincle signalling was significantly elevated in active human CD and experimental colitis, and macrophages were the principal leukocyte subset that upregulate Mincle signalling. Mincle deficiency and Syk pharmacological inhibition ameliorated the colitis by reducing induced macrophage pyroptosis, and activation of Mincle with the agonist aggravated the intestinal inflammation. The ex vivo studies demonstrated that activation of Mincle signalling promoted the release of proinflammatory cytokines, whereas its absence restricted release of proinflammatory cytokines from pyroptosis of macrophages. In addition, Mincle/Syk signalling in macrophages could promote the production of chemokines to recruit neutrophils by activating mitogen-activated protein kinase [MAPK] during intestinal inflammation. CONCLUSIONS: Mincle signalling promotes intestinal mucosal inflammation by inducing macrophage pyroptosis. Modulation of the Mincle/Syk axis emerges as a potential therapeutic strategy to target inflammation and treat CD.

Effect of PI3K/PKB signal pathway inhibitor wortmannin pretreatment on intestinal barrier function in severe acute pancreatitic rats.

BACKGROUND: It is well-known that severe acute pancreatitis (SAP) due to infection is mainly caused by intestinal bacterial translocation. The intestinal barrier is tasked with preventing intestinal pathogenic bacteria and toxins from reaching the parenteral tissues through the intestinal wall. Therefore, maintaining intestinal barrier function may be the key to preventing damage from acute pancreatitis (AP). The phosphatidylinositol 3-kinase/protein kinase B pathway (PI3K/PKB) plays a role in AP. However, the exact effect of PI3K/PKB on injury associated with SAP has not yet been found. OBJECTIVES: The present study was aimed at investigating the impact of wortmannin (WT), a PI3K/PKB inhibitor, on intestinal barrier function in SAP rats. MATERIAL AND METHODS: The rats were divided into 3 groups: 1) the Sham Surgery group (SS), whose duodenum and pancreas were flipped 3 times (n = 18); 2) the pancreatitis group (SAP), who were injected through retrograde pancreatic duct injection with 5% sodium taurocholate (n = 18); and 3) the WSAP intervention group (SAP+WT). Serum alpha-amylase levels, plasma endogenous endotoxin, hematoxylin-eosin (H&E) staining, intestinal mucosa electron microscopy, intestinal permeability, and expression of p-PKB (phosphorylated protein kinase B) were measured. RESULTS: In our findings under an electron microscope, the SAP group presented cell edema and mitochondrial vacuolated degeneration, sparsely arranged microvilli, tight junction damage, and widening, while the WSAP group exhibited less change and lower pancreas scores (7.4 ±1.14, 10.2 ±1.48 and 12.0 ±1.58 for 3 h, 6 h and 12 h, respectively) (p < 0.05). Furthermore, the plasma endogenous endotoxin levels and Evans blue content of the WSAP group was significantly lower at all timepoints than in the SAP group (p < 0.05). Western blotting showed that p-PKB expression was lower in the WSAP group than in the SAP group (p < 0.05). Our study suggests that WT relieves intestinal permeability changes in SAP rats and may be dose-dependent. CONCLUSIONS: The PI3K/PKB signal pathway may involve SAP-related intestinal injuries and WT may relieve SAP intestinal injuries through the PI3K/PKB pathway.

Sandwich-structure hydrogels implement on-demand release of multiple therapeutic drugs for infected wounds.

Wound infections bring huge challenges to clinical practice. A series of approaches are involved in the management of infected wounds including use of antibacterial agents, granulation tissue regeneration and scar prevention. In this study, we fabricated a sandwich-structure hydrogel dressing through layer-by-layer assembly of films and hydrogels. By pre-loading silver nanoparticles (AgNPs), vascular endothelial growth factors (VEGF) and ginsenoside Rg3 (Rg3) into each layer of the sandwich compound, this hydrogel could realize the sequential release of these drugs onto infected wound beds as demanded. Moreover, altering the thickness of middle layer could further change the drug delivery patterns characterized by delay at the initial releasing timepoint. When applying this dressing on infected wounds of rabbit ears, we found it could alleviate infection-induced inflammation, promote granulation tissue regeneration and inhibit scar formation. Collectively, the design of sandwich-structure hydrogels was facilitated to deliver specific drugs sequentially during their therapeutic time window for complicated diseases and has shown potential applications in infected wounds.

CMIP is oncogenic in human gastric cancer cells.

Gastric cancer is one of the most common cancers and the second leading cause of cancer­associated mortality worldwide. Recurrence, metastasis and resistance to drug treatment are the main barrier to survival of patients with advanced stage gastric cancer. Further study of the molecular mechanisms involved will improve the therapeutic options for gastric cancer. In a previous study, c­Maf was discovered as an oncogene transduced in the avian AS42 retrovirus, and was found to be overexpressed in multiple myeloma and angioimmunoblastic T­cell lymphoma. c­Maf inducing protein (CMIP) is involved in the c­Maf signaling pathway, which was reported to serve an important role in human minimal change nephrotic syndrome and in human reading and language related behavior. However, the relationship between CMIP and human gastric cancer has not yet been reported. In the present study, CMIP protein levels in gastric cancer tissues and cells were measured using immunohistochemistry and western blot analysis; the expression of CMIP protein was significantly higher in gastric cancer tissues compared with normal gastric tissues. Expression was positively associated with poorer clinical parameters, relapse­free survival and overall survival. Furthermore, using cell counting, Cell Counting Kit­8, colony formation, wound healing and Transwell assays, together with flow cytometry, CMIP depletion by RNA interference was observed to reduce the capacity of gastric cancer cells to proliferate and migrate in vitro. Furthermore, the upstream and downstream genes of CMIP were analyzed by luciferase reporter assay and reverse transcription quantitative polymerase chain reaction, which indicated that CMIP was a direct target of miR­101­3p. In addition, CMIP knockdown was observed to result in the downregulation of MDM2 and mitogen activated protein kinase (MAPK) expression at the mRNA level. In conclusion, CMIP demonstrated an oncogenic role in human gastric cancer cells. Furthermore, microRNA­101­3p, MDM2 and MAPK were involved in the CMIP signaling pathway in gastric cancer. CMIP could be a novel target for further investigation in the clinical therapeutic management of gastric cancer.

Zinc supplement modulates oxidative stress and antioxidant values in rats with severe acute pancreatitis.

Oxidative stress is a main factor in the pathogenesis of severe acute pancreatitis (SAP). The ability of zinc (Zn) to retard oxidative processes has been recognized for many years. This study aims to examine the levels of free oxygen radicals and antioxidant enzyme in SAP rats and know the effect of Zn supplementation on free oxygen radicals and antioxidant system in rats with SAP. Forty-five male Wistar rats were divided into three groups-the SAP group (n=15), the Zn-treated group (n=15), and the controlled group (n=15). For the SAP group, sodium taurocholate is injected into the pancreatic duct to induce SAP; for the Zn-treated group, Zn (5 mg/kg) is subcutaneously injected immediately after injection of 5% sodium taurocholate. Firstly, the activity of erythrocyte glutathione peroxidase (GSH-Px), erythrocyte superoxide dismutase (SOD), and the content of plasma malondialdehyde (MDA), which are the toxic products of oxidative stress, is measured. Secondly, the levels of free oxygen radicals in the liver and kidney are detected. The result showed that the activity of GSH-Px and SOD was lower in the SAP group than that in the controlled group, although the content of plasma MDA increased. However, the activity of SOD and GSH-Px in the Zn-treated group was not significantly decreased after comparing with the controlled group; in the mean time, the content of MDA was not significantly increased either. Moreover, the content of free radical in liver and kidney was higher in the SAP group compared with the controlled group, but the content of free radical in the Zn-treated group was not higher than that in the controlled group (p>0.05). All of the above indicated that Zn may recover the activity of free radical-scavenging enzymes and decrease the content of free radical for the SAP group rats. In conclusion, the content of free radical increase may be one of the reasons that SAP rats are injured, and it is possible for Zn to be used to treat SAP through scavenging free radical and increasing the activity of SOD and GSH-Px of erythrocyte.

[Effects of substrate species on fermentative hydrogen production].

Biohydrogen production by anaerobic sludge was studied by using wastewater as substrate in batch process. Hydrogen production potential of different substrate species, as well as the composition of fermentation product in liquid phase, was studied in the batch culture experiments. The hydrogen production and bacterial growth dynamics were also analyzed. The experiment results demonstrated that the optimal substrate was glucose for hydrogen production. It could be obtained maximum cumulative hydrogen production 67.21 L/mol, hydrogen yield 3.23 mol/mol and hydrogen content 49.52%. The butyrate and acetate were main liquid end products, occupied 26.76%-40.49% of acetate, 37.60%-58.07% of butyrate, implying that it is butyrate-type fermentation. Butyrate/acetate could be used as the indicator for evaluating the effectiveness of H2 production, with that the higher butyrate/acetate, the higher the hydrogen yield. ORP was less than -300 mV during fermentation indicating the experiment was anaerobic. A modified Gompertz model can adequately describe the H2 production and bacterial growth.

Fluoride and children's intelligence: a meta-analysis.

This paper presents a systematic review of the literature concerning fluoride that was carried out to investigate whether fluoride exposure increases the risk of low intelligence quotient (IQ) in China over the past 20 years. MEDLINE, SCI, and CNKI search were organized for all documents published, in English and Chinese, between 1988 and 2008 using the following keywords: fluorosis, fluoride, intelligence, and IQ. Further search was undertaken in the website www.fluorideresearch.org because this is a professional website concerning research on fluoride. Sixteen case-control studies that assessed the development of low IQ in children who had been exposed to fluoride earlier in their life were included in this review. A qualitative review of the studies found a consistent and strong association between the exposure to fluoride and low IQ. The meta-analyses of the case-control studies estimated that the odds ratio of IQ in endemic fluoride areas compared with nonfluoride areas or slight fluoride areas. The summarized weighted mean difference is -4.97 (95%confidence interval [CI] = -5.58 to -4.36; p < 0.01) using a fixed-effect model and -5.03 (95%CI = -6.51 to 3.55; p < 0.01) using a random-effect model, which means that children who live in a fluorosis area have five times higher odds of developing low IQ than those who live in a nonfluorosis area or a slight fluorosis area.

Biohydrogen production from cattle wastewater by enriched anaerobic mixed consortia: influence of fermentation temperature and pH.

Experiments were conducted to select a natural mixed microflora seed source and investigate the effect of temperature and pH on fermentative hydrogen (H2) production from cattle wastewater by sewage sludge. Sewage sludge was shown to have higher cumulative H2 production than other inoculum collected from cow dung compost, chicken manure compost, and river sludge. Experimental results show that H2 production from cattle wastewater was significantly affected by both pH and temperature of the culture. The maximum H2 yield was obtained at pH 5.5. H2 yield and the ratio of butyrate/acetate (Bu/Ac) followed a similar production trend, suggesting that butyrate formation might favor H2 production. The optimal temperature for H2 production from cattle wastewater was 45 degrees C with peak values of H2 production (368 ml), hydrogen yield of 319 ml H2/g chemical oxygen demand (COD) consumed, and butyrate/acetate ratio of 1.43. Presence of ethanol and propionic acid indicated decreased hydrogen production; their concentrations were also affected by pH and temperature. A modified Gompertz model adequately described H2 production and bacterial growth.