Blue Laser Triggered Hemostatic Peptide Hydrogel for Gastrointestinal Bleeding Treatment.

In an emergency, nonvariceal upper gastrointestinal bleeding (NVUGIB), endoscopic hemostasis is considered the gold standard intervention. However, current endoscopic hemostasis is very challenging to manage bleeding in large-diameter or deep lesions highly prone to rebleeding risk. Herein, a novel hemostatic peptide hydrogel (HPH) is reported, consisting of a self-assembly peptide sequence CFLIVIGSIIVPGDGVPGDG (PFV) and gelatin methacryloyl (GelMA), which can be triggered by blue laser endoscopy (BLE) for nonvariceal upper gastrointestinal bleeding treatment without recurring bleeding concerns. Upon contact with GelMA solution, PFV immediately fibrillates into ß-sheet nanofiber and solvent-induced self-assembly to form HPH gel. HPH nanofiber networks induced ultrafast coagulation by enveloping blood cells and activating platelets and coagulation factors even to the blood with coagulopathy. Besides its remarkable hemostatic performance in artery and liver injury models, HPH achieves instant bleeding management in porcine NVUGIB models within 60 s by preventing the rebleeding risk. This work demonstrates an extraordinary hemostatic agent for NVUGIB intervention by BLE for the first time, broadening potential application scenarios, including patients with coagulopathy and promising clinical prospects.

Isolation of a surfactin-producing strain of Bacillus subtilis and evaluation of the probiotic potential and antioxidant activity of surfactin from fermented soybean meal.

BACKGROUND: Surfactin, usually produced by microbial metabolism, has many advantages including low toxicity, high biodegradability, and stability at extreme pH levels and temperatures, making it suitable for industry. However, its commercial production has not yet been achieved. RESULTS: A strain with a strong surfactin-producing ability was isolated and identified as Bacillus subtilis SOPC5, based on the appearance of colonies, microscopic observation, and 16S rDNA sequencing. The isolate exhibited significant tolerance to acid, bile, gastric, and intestinal juices, and was sufficiently susceptible to antibiotics. Bacillus subtilis SOPC5 showed high levels of auto-aggregation and surface hydrophobicity, and a strong capacity to secrete protease, amylase, and cellulase. The strain also exhibited antibacterial activity against Staphylococcus aureus 10 306 with a antibacterial circle diameter of 18.0 ± 1.1 mm. The maximal yield of surfactin (1.32 mg mL-1) was obtained by fermenting soybean meal (SBM) using the isolate under the following conditions: SBM 86 g L-1, inoculation 1.5 × 107 CFU mL-1, FeSO4 1.2 mg L-1, MnSO4 2.6 mg L-1, MgSO4 0.5 mg mL-1, L-Glu 4 mg L-1, temperature 33 °C, duration 120 h, and shaking at 210 rpm. The purity of surfactin was 97.42% as measured by high-performance liquid chromatography (HPLC). The half inhibitory concentration (IC50) values for surfactin to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2-azino-bis-(3-ethylbenzothiazoline-6-sulfonic acid) radical cation (ABTS·+) were 1.275 ± 0.11 and 0.73 ± 0.08 mg mL-1, respectively. CONCLUSION: This study provides a scientific basis for the application of B. subtilis SOPC5 (as a potential probiotic) and the preparation of its metabolic product (surfactin). © 2024 Society of Chemical Industry.

Plant mucus-derived microgels: Blood-triggered gelation and strong hemostatic adhesion.

Arrest of bleeding usually applies clotting agents to trigger coagulation procedures or adhesives to interrupt blood flow through sealing the vessel; however, the efficiency is compromised. Here, we propose a concept of integration of hemostasis and adhesion via yam mucus's microgels. The mucus microgels exhibit attractive attributes of hydrogel with uniform size and shape. Their shear-thinning, self-healing and strong adhesion make them feasible as injectable bioadhesion. Exceptionally, the blood can trigger the microgels' gelation with the outcome of super extensibility, which leads to the microgels a strong hemostatic agent. We also found a tight gel adhesive layer formed upon microgels' contacting the blood on the tissue, where there is the coagulation factor XIII triggered to form a dense three-dimensional fibrin meshwork. The generated structures show that the microgels look like hard balls in the dispersed phase into the blood-produced fibrin mesh of a soft net phase. Both phases work together for a super-extension gel. We demonstrated the microgels' fast adhesion and hemostasis in the livers and hearts of rabbits and mini pigs. The microgels also promoted wound healing with good biocompatibility and biodegradability.

Analyzing Mushroom Structural Patterns of a Highly Compressible and Expandable Hemostatic Foam for Gastric Perforation Repair.

Nature presents the most beautiful patterns through evolving. Here, a layered porous pattern in golden ratio (0.618) is reported from a type of mushroom -Dictyophora Rubrovalvata stipe (DRS). The hierarchical structure shows a mathematical correlation with the golden ratio. This unique structure leads to superior mechanical properties. The gradient porous structure from outside to innermost endows it with asymmetrical hydrophilicity. A mathematical model is then developed to predict and apply to 3D printed structures. The mushroom is then explored to repair gastric perforation because the stomach is a continuous peristaltic organ, and the perforated site is subject to repeated mechanical movements and pressure changes. At present, endoscopic clipping is ineffective in treating ulcerative perforation with fragile surrounding tissues. Although endoscopic implant occlusion provides a new direction for the treatment of gastric ulcers, but the metal or plastic occluder needs to be removed, requiring a second intervention. Decellularized DRS (DDRS) is found with asymmetric water absorption rate, super-compressive elasticity, shape memory, and biocompatibility, making it a suitable occluder for the gastric perforation. The efficacy in blocking gastric perforation and promoting healing is confirmed by endoscopic observation and tissue analysis during a 2-month study.

Enhancing the growth of thermophilic Bacillus licheniformis YYC4 by low-intensity fixed-frequency continuous ultrasound.

The effect of low-intensity fixed-frequency continuous ultrasound (LIFFCU) on the growth of Bacillus licheniformis YYC4 was investigated. The changes in morphology and activity of the organism, contributing to the growth were also explored. Compared with the control, a significant increase (48.95%) in the biomass of B. licheniformis YYC4 (at the logarithmic metaphase) was observed following the LIFFCU (28 kHz, 1.5 h and 120 W (equivalent to power density of 40 W/L)) treatment. SEM images showed that ultrasonication caused sonoporation, resulting in increased membrane permeability, evidenced by increase in cellular membrane potential, electrical conductivity of the culture, extracellular protein and nucleic acid, and intracellular Ca2+ content. Furthermore, LIFFCU action remarkably increased the extracellular protease activity, volatile components of the culture medium, microbial metabolic activity, and spore germination of the strain. Therefore, LIFFCU could be used to efficiently promote the growth of targeted microorganisms.

Biosynthetic Plastics as Tunable Elastic and Visible Stent with Shape-Memory to Treat Biliary Stricture.

Common biliary tract is ≈4 mm in diameter to deliver bile from liver to small intestine to help digestion. The abnormal narrowing leads to severe symptoms such as pain and nausea. Stents are an effective treatment. Compared with non-degradable stents which require repeated removal, biodegradable stents have the advantage of reducing secondary injury related to endoscopic operation and patient burden. However, current biodegradable materials may cause tissue hyperplasia and the treatment method does not target etiology of stricture. So recurrence rates after biodegradable stent implantation are still high. Here, a biodegradable helical stent fabricated from biosynthetic P(3HB-co-4HB) is reported. Tunable properties can be acquired through altering culture substrates. Stent shows shape memory in various solvents. The stent has an optimized design with helical structure and outer track. The self-expanding of helical structure and double drainage realized by outer track greatly improve drainage of bile. Importantly, stent-loading triamcinolone acetonide can inhibit proliferation of fibroblasts and reduce incidence of restricture. Therapeutic effect is also demonstrated in minipigs with biliary stricture. The results of minipig experiments show that biliary duct in treatment group is unobstructed and tissue hyperplasia is effectively inhibited.

Endoscopy Deliverable and Mushroom-Cap-Inspired Hyperboloid-Shaped Drug-Laden Bioadhesive Hydrogel for Stomach Perforation Repair.

Gastrointestinal tract perforation is a full-thickness injury that causes bleeding and fatal infection of the peritoneum. This condition worsens in an acidic gastric environment which interferes with the normal coagulation cascade. Current endoscopic clips to repair gastric perforations are ineffective, and metal or plastic occluders need secondary surgery to remove them. Herein, we report a self-expandable, endoscopy deliverable, adhesive hydrogel to block gastric perforation. We found the nanosilica coating significantly enhanced the adhesive strength even under a simulated strong acidic stomach environment. The developed device was disulfide cross-linked for the reducible degraded gel. By loading with vonoprazan fumarate (VF) and acidic fibroblast growth factor (AFGF), the hyperboloid-shaped device can have a sustained drug release to regulate intragastric pH and promote wound healing. The gel device can be compressed and then expanded like a mushroom when applied in an acute gastric perforation model in both rabbits and minipigs. By utilizing a stomach capsule robot for remotely monitoring the pH and by immunohistochemical analysis, we demonstrated that the compressible hyperboloid-shaped gel could stably block the perforation and promoted wound healing during the 28 days of observation. The real-time pH meter demonstrated that the gel could control intragastric pH above 4 for nearly 60 h to prevent bleeding.

Aligned nanofibrous collagen membranes from fish swim bladder as a tough and acid-resistant suture for pH-regulated stomach perforation and tendon rupture.

BACKGROUND: Wound closure in the complex body environment places higher requirements on suture's mechanical and biological performance. In the scenario of frequent mechanical gastric motility and extremely low pH, single functional sutures have limitations in dealing with stomach bleeding trauma where the normal healing will get deteriorated in acid. It necessitates to advance suture, which can regulate wounds, resist acid and intelligently sense stomach pH. METHODS: Based on fish swim bladder, a double-stranded drug-loaded suture was fabricated. Its cytotoxicity, histocompatibility, mechanical properties, acid resistance and multiple functions were verified. Also, suture's performance suturing gastric wounds and Achilles tendon was verified in an in vivo model. RESULTS: By investigating the swim bladder's multi-scale structure, the aligned tough collagen fibrous membrane can resist high hydrostatic pressure. We report that the multi-functional sutures on the twisted and aligned collagen fibers have acid resistance and low tissue reaction. Working with an implantable "capsule robot", the smart suture can inhibit gastric acid secretion, curb the prolonged stomach bleeding and monitor real-time pH changes in rabbits and pigs. The suture can promote stomach healing and is strong enough to stitch the fractured Achilles tendon. CONCLUSIONS: As a drug-loaded absorbable suture, the suture shows excellent performance and good application prospect in clinical work.

Nature-Derived Okra Gel as Strong Hemostatic Bioadhesive in Human Blood, Liver, and Heart Trauma of Rabbits and Dogs.

Bioadhesive performance can be compromised due to bleeding. Bleeding increases mortality. Adhesives with hemostatic function are of great significance. A sustainable and robust hemostatic bioadhesive from okra is reported. The adhesive strength reaches around three and six-fold higher than commercial fibrin on pigskin and glass, respectively. The okra gel presents high-pressure resistance and great underwater adhesive strength. In human blood experiments, the okra gel can activate platelets, enhance the adhesion of activated platelets, and release coagulation factors XI and XII. By forming a fast gel layer and closely adhering to the wound, it can quickly stop bleeding in the liver and heart of rabbits and dogs. Meanwhile, okra gel can cause platelet activation at the wound site and further strengthen its hemostatic performance. It is biocompatible, biodegradable, and can promote wound healing and shows potential as a sustainable bioadhesive, especially in the scenario of significant hemorrhage.

Effects of perchlorate on growth of four wetland plants and its accumulation in plant tissues.

Perchlorate contamination in water is of concern because of uncertainties about toxicity and health effects, impact on ecosystems, and possible indirect exposure pathways to humans. Therefore, it is very important to investigate the ecotoxicology of perchlorate and to screen plant species for phytoremediation. Effects of perchlorate (20, 200, and 500 mg/L) on the growth of four wetland plants (Eichhornia crassipes, Acorus calamus L., Thalia dealbata, and Canna indica) as well as its accumulation in different plant tissues were investigated through water culture experiments. Twenty milligrams per liter of perchlorate had no significant effects on height, root length, aboveground part weight, root weight, and oxidizing power of roots of four plants, except A. calamus, and increasing concentrations of perchlorate showed that out of the four wetland plants, only A. calamus had a significant (p<0.05) dose-dependent decrease in these parameters. When treated with 500 mg/L perchlorate, these parameters and chlorophyll content in the leaf of plants showed significant decline contrasted to control groups, except the root length of E. crassipes and C. indica. The order of inhibition rates of perchlorate on root length, aboveground part weight and root weight, and oxidizing power of roots was: A. calamus > C. indica > T. dealbata > E. crassipes and on chlorophyll content in the leaf it was: A. calamus > T. dealbata > C. indica > E. crassipes. The higher the concentration of perchlorate used, the higher the amount of perchlorate accumulation in plants. Perchlorate accumulation in aboveground tissues was much higher than that in underground tissues and leaf was the main tissue for perchlorate accumulation. The order of perchlorate accumulation content and the bioconcentration factor in leaf of four plants was: E. crassipes > C. indica > T. dealbata > A. calamus. Therefore, E. crassipes might be an ideal plant with high tolerance ability and accumulation ability for constructing wetland to remediate high levels of perchlorate polluted water.