Fiber Deposition Research Articles

Perfluorooctanoic acid induced lung toxicity via TGF-β1/Smad pathway, crosstalk between airway hyperresponsiveness and fibrosis: withdrawal impact.

Perfluorooctanoic acid (PFOA) is an environmental persistent agent to which humans are exposed daily through food and water. This study investigated the lung toxic effects induced by ingested PFOA (30 mg/kg/day) for 8 weeks in adult male rats and the impact following 8 weeks of its withdrawal. PFOA increased MDA and reduced TAC inducing oxidative stress. It induced airway hyperresponsiveness (AHR) via increased bronchoalveolar lavage fluid (BALF) IL-4, IL-5, IL-13, IL-9, eosinophil count, TNF-α, and IL-1ß; reduced IL-12; increased serum IgE; and increased urocortin expression in lung tissues. Moreover, it induced pulmonary fibrosis via increased serum KL-6, and SFTP-D, altered pulmonary structure, and increased deposition of collagen fibers in lung tissues. Furthermore, it increased TGF-β1, Smad2, and Smad3 and reduced Smad7 gene expression in lung tissues. These gene alterations were positively correlated with AHR and fibrosis-related factors. The recovered lung upon PFOA withdrawal showed complete resolution of oxidative stress and slight amelioration of other studying parameters. Exposure to PFOA induced lung toxicity by disrupting the TGF-β1/Smad signaling pathway, which acts as a crosstalk between AHR and fibrosis. Additionally, PFOA altered pulmonary architecture, triggered inflammation, and caused oxidative stress. The lung exhibited partial alleviation upon recovery.

Study on Deposition of Coaxial Electrospinning Fibers by Coaxial Auxiliary Flow Field

Gas-assisted coaxial electrospinning (GACES) is a simple and general method for the mass preparation of coaxial nanofiber membranes, which has great industrial potential. However, in the manufacturing process, due to the bending instability of the jet in the electric field and the pulling effect of the gas flow field, the deposition uniformity of the fiber is still a big problem. Through finite element simulation analysis of the flow field in the manufacturing process and the construction of the jet mechanics model after adding the flow field, the influence mechanism of coaxial auxiliary flow on the fiber deposition area and its uniformity was successfully revealed in this research. Finally, the deposition area and thickness uniformity of coaxial fibers are increased by 3 times (the deposition area: 19.63 cm2 → 78.50 cm2) and 2.34 times (the standard variance: 3 μm2 → 10 μm2) by gas-assisted coaxial electrospinning. At the same time, the coaxial auxiliary gas flow also reduces the coaxial fiber diameter by 36.9% (the average fiber diameter: 241 nm ± 5 nm → 152 nm ± 23 nm) and the distribution range by 66% (the standard variance: 1.5 × 102 nm2 → 51 nm2). This research provides a reliable idea and experimental basis for homogeneous preparation of coaxial nanofiber membranes.

The promoting effect of Balanus albicostatus cement protein 19k (Balcp19k) on wound healing by regulating fibroblast migration and relieving early-stage inflammation responses.

The high incidence of skin wounds (e.g., burns, diabetic ulcers, venous ulcers, pressure sores, and radiation injuries) remains a significant challenge in clinical settings. Dressing materials, infused with bioactive components, are essential and extensively utilized in specific circumstances. According to traditional Chinese medicine therapeutic regimens, powders made of the flesh/shells of Balanus albicostatus were used to treat sores due to their ability to alleviate inflammatory responses. Nevertheless, information is scarce regarding the effective components and the pharmacological mechanisms involved. In this work, purified Balanus albicostatus cement protein 19k (Balcp19k) was obtained as a single-component material via an E. coli-based heterologous expression system. It had the potential to promote fibroblast proliferation and migration, which were crucial for wound healing. Immunofluorescence revealed that Balcp19k treatment promoted M2 macrophage transformation in wound tissues. Correspondingly, the expression of inflammation-related genes (e.g., IL-6, TNF-α, and IFN-γ) was significantly reduced (p<0.05). Moreover, histological examination indicated that this treatment accelerated skin-wound healing by promoting collagen fiber deposition and angiogenesis, and restraining inflammatory cell infiltration in the full-thickness skin of mice. In conclusion, Balcp19k is a biocompatible, effective constituent found in Balanus albicostatus. This bioactive protein could be novel therapeutic material for wound healing, with ability to regulate fibroblast migration, alleviate early-stage inflammatory responses, and enhance collagen fiber deposition and angiogenesis.

Polypropylene Mesh Coated with Dual Cross‐Linked Hyaluronic Acid/Polyvinyl Alcohol Composite Hydrogel with Antiadhesion and Angiogenesis Properties for Abdominal Wall Repair

AbstractDevelopment of an antiadhesion polypropylene (PP) mesh in hernia repair is a recognized need because its efficacy is limited by severe abdominal adhesions. The porous structure of PP mesh can facilitate the integration between prosthetic material and abdominal tissue and promote the repair of abdominal wall defect. Herein, an antiadhesion composite hydrogel coating composed of polyvinyl alcohol (PVA) and hyaluronic acid methacrylate (HAMA) is fabricated on the surface of PP mesh through ultraviolet photopolymerization combined with freezing–thawing method. The resulted composite hydrogel coated PP mesh retain 43.33% of the pore structure by this way. In vitro tests proved the as‐prepared PP mesh exhibit excellent hydrophilicity and biocompatibility. Meanwhile, the hydrogel coating shows good stability on the surface of PP mesh in phosphate buffered saline medium. After implantation in a rat abdominal wall defect model, the modified PP mesh effectively prevents the formation of adhesion by reducing inflammatory response and suppressing excessive deposition of collagen fiber. Immunohistochemical staining results demonstrate that the modified PP mesh can not only decrease the expression of IL‐6, TNF‐α, and CD68 but also promote the expression of CD31. Thus, this type of PP mesh with preventing postoperative adhesions and improving angiogenesis may be a promising clinical prosthetic material.

Inula japonica Thunb. and its active compounds ameliorate airway inflammation by suppressing JAK-STAT signaling.

Asthma, a chronic inflammatory disease, remains a global health challenge due to its complex pathophysiology and the limited treatment efficacy. This study explored the effect of Inula japonica Thunb. water extract (IJW) on asthma and its protective mechanisms. To assess the effects of IJW, we established an experimental asthma model in BALB/c mice using ovalbumin (OVA). Airway hyper-responsiveness (AHR) in response to methacholine was measured. We quantified inflammatory cell infiltration and cytokine and chemokine levels in bronchoalveolar lavage fluid (BALF), as well as total IgE levels in serum. Staining with hematoxylin and eosin and periodic acid-Schiff was used to examine the impact of IJW on lung pathology. We performed RNA sequencing to identify differentially expressed genes, which were subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. We used interleukin (IL)-4/IL-13-treated human bronchial epithelial (HBE) cells to explore the associated mechanisms. IJW showed therapeutic effects against OVA-induced asthma by alleviating AHR, peribronchial inflammation, mucus hypersecretion, and collagen fiber deposition. It reduced total IgE levels in the serum and IL-4, IL-5, IL-13, eotaxin, macrophage-derived chemokines, and periostin levels in BALF. In IL-4/IL-13-treated HBE cells, IJW and its components suppressed the Janus kinase-signal transducer and activator of the transcription (JAK-STAT) signaling. These findings support IJW's potential as a pharmacological agent for allergic airway inflammation and asthma.

P0072 Unveiling mesenteric and intestinal changes in Crohn’s disease: insights into fibrosis from surgical specimens

Abstract Background Recent studies have emphasized the role of mesenteric changes, including creeping fat, alongside intestinal alterations in the progression of Crohn's disease (CD). This study aims to investigate intestinal fibrosis and mesenteric changes using tissues obtained from CD patients who underwent surgery for complications such as strictures and perforations. Methods From September 2023 to September 2024, intestinal (CD-Inflamed-Bowel/CD-Uninflamed-Bowel) and mesenteric tissues (CD-Inflamed-Mes/CD-Uninflamed-Mes/ CD-Uninvolved-Mes) were collected from nine CD patients who underwent surgery. Additionally, intestinal (Normal-Bowel) and mesenteric tissues (Normal-Mes) were obtained from one patient who underwent anterior resection for adenoma. Specimens were obtained from the small intestine (4 patients) and the colon (5 patients). Samples were analyzed for morphological changes (H&amp;E staining), collagen deposition (Masson’s trichrome), and fibrosis marker expression (qPCR). Results Preoperative CT or MR enterography revealed the presence of creeping fat in all nine CD patients, with five showing strictures accompanied by upstream bowel dilatation. In intestinal tissues, increased collagen fiber deposition was observed in CD-Inflamed-Bowel compared to CD-Uninflamed-Bowel, whereas mesenteric tissues showed no significant differences in collagen deposition among Uninvolved, Uninflamed, and Inflamed groups. qPCR analysis of intestinal tissues revealed significantly higher expression of the fibrosis marker COL1A1 in CD-Inflamed-Bowel compared to Normal-Bowel and CD-Uninflamed-Bowel (119.9 ± 260 vs. 1.0 ± 0.0 vs. 1.0 ± 0.7, P = 0.041). In mesenteric tissues, COL1A1 expression was significantly elevated in CD patients compared to controls (28.0 ± 7.7 vs. 1.0 ± 0.0, P = 0.002), though no significant differences in COL1A1 expression were found among Uninvolved, Uninflamed, and Inflamed mesenteric tissues within the same patient (17.7 ± 3.7, 25.1 ± 9.2, 41.0 ± 21.2, P = 0.9372). Other fibrosis markers (Vimentin, TGF-β, MMP-1, CHI3L1, CXCL1, and PDPN) showed similar trends. Conclusion This study highlights inflammatory and fibrotic changes in the intestine and mesentery during CD progression. Notably, mesenteric fibrosis was evident even in uninvolved intestinal segments without active inflammation, suggesting mesenteric inflammation and fibrosis may precede intestinal involvement. These findings support the mesentery as a novel potential target for early treatment for disease progression of CD.

Hypermethylation of Hif3a and Ifltd1 is associated with atrial remodeling in pressure-overload murine model

Atrial remodeling is a major pathophysiological mechanism of atrial fibrillation (AF). Atrial remodeling progresses with aging and background diseases, including hypertension, heart failure, and AF itself. However, its mechanism of action and reversibility have not been completely elucidated. In this study, we investigated the involvement of DNA methylation in atrial remodeling. Mice underwent transverse aortic constriction (TAC) to generate a pressure overload model. After 14 days, the TAC-operated mice showed a significant increase in the atrium/body weight ratio and deposition of collagen fibers in the atria. A comprehensive analysis using RNA-sequencing (RNA-Seq) and methyl-CpG-binding domain sequencing (MBD-Seq) in the left atrial tissue identified Hif3a and Ifltd1 as showing increased DNA methylation in their promoter regions and decreased RNA expression. In addition, we created a transient pressure overload model by removing the aortic constriction 3 or 7 days after the initial TAC procedure (R3 or R7 groups). A reduction in RNA expression was achieved at R3 for Hif3a and at R7 for Ifltd1. Heterozygous Dnmt1 gene-targeting mice (Dnmt1mut) showed disappearance of the reduction in RNA expression and an increase in the atrium/body weight ratio. Altogether, DNA methylation contributed to at least part of atrial remodeling in the pressure overload mouse model.

Development of Electrospinning Setup for Vascular Tissue-Engineering Application with Thick-Hierarchical Fiber Alignment.

Tissue engineering holds promise for vascular repair and regeneration by mimicking the extracellular matrix of blood vessels. However, achieving a functional and thick vascular wall with aligned fiber architecture by electrospinning remains a significant challenge. A novel electrospinning setup was developed that utilizes an auxiliary electrode and a spring. The impact of process parameters on fiber size and morphology wasinvestigated. The structure and functions of the scaffolds were evaluated through material characterization and assessments of cellular biocompatibility. The new setup enabled controlled deposition of fibers in different designed orientations. The fabricated small-diameter vascular scaffolds consisted of an inner layer of longitudinally oriented fibers and an outer layer of circumferentially oriented fibers (L + C vascular scaffold). Key parameters, including rotational speed, the utilization of the auxiliary electrode, and top-to-collector distance (TCD) significantly influenced fiber orientation. Additionally, voltage, TCD, feed rate, needle size, auxiliary electrode and collector-auxiliary electrode distance affected fiber diameter and distribution. Mechanical advantages and improved surface wettability of L + C vascular scaffold were confirmed through tensile testing and water contact angle. Cellular experiments indicated that L + C vascular scaffold facilitated cell adhesion and proliferation, with human umbilical vein endothelial cells and smooth muscle cells attaching and elongating along the fiber direction of the inner and outer layer, respectively. This study demonstrated the feasibility of fabricating fiber-aligned, thick-walled vascular scaffolds using a modified electrospinning setup. The findings provided insights into how the auxiliary electrode, specific collector influenced fiber deposition, potentially advancing biomimetic vascular scaffold engineering.

Gentisic acid protects Sprague-Dawley rats from myocardial infarction through reversing electrocardiographical, biochemical and histopathological abnormalities.

Gentisic acid (GA), a cytochrome P450 metabolite of the antiplatelet drug aspirin, exhibits smooth muscle relaxant, antiatherogenic, and antioxidant activities. It also has a protective role in hypertrophic heart failure, suggesting its role in the management of myocardial infarction (MI). This study aimed to explore the protective activity of GA in isoproterenol (ISO)-induced MI in Sprague-Dawley (SD) rats in-vivo, followed by mechanistic investigation ex-vivo. SD rats were pretreated with different doses (5, 10, 15, and 20mg/kg, i.p.) of GA for 21 days, followed by subcutaneous administration of ISO (85mg/kg) on the 20th and 21st days. At the end of the experiment, electrocardiograph (ECG), blood pressure, myocardial injury marker enzymes, infarct size, lipid profile, and histological changes in myocardium were carried out. The possible underlying mechanisms were explored ex-vivo. GA prevented the ISO-induced changes in ECG parameters in rats in a dose-dependent manner. GA also reversed the fall in blood pressure associated with ISO treatment. GA diminished the elevated cardiac biomarkers and limited the infarcted area size (8%) indicated by decrease in heart weight to body weight ratio. GA ameliorated the inflammation, edema, and necrosis and reduced collagen fiber deposition associated with ISO-induced MI. The results suggest that GA is an effective cardioprotective agent in rats by reversing ischemic changes in ECG and correcting histopathological and biochemical changes.

Microneedle drug delivery system based on hyaluronic acid for improving therapeutic efficiency of hypertrophic scars.

Hypertrophic scar (HS) is a disease with excessive skin fibrosis and collagen disorder, which is generally caused by abnormal wound repair process after burn and trauma. Although intralesional injection of 5-fluorouracil (5-Fu) has been used in clinical treatment of HS, the patients' compliance of injection treatment is poor. In this study, a double-layer dissolution microneedle (MN) containing asiaticoside (AS) and 5-Fu was designed for the treatment of HS. Biological macromolecules materials affected the formability, drug release, and hardness of MNs. Therefore, several types of biomacromolecules, including hyaluronic acid (HA), chitosan, and sodium alginate, which could be used to prepare MNs, underwent prescription optimization experiments and the optimized MN prescriptions were obtained. In vitro characterization showed that the MN was sufficient to deliver drugs through the skin. Animal in vivo experiments showed that AS and 5-Fu can synergistically treat HS, significantly reduce the abnormal proliferation of fibroblasts and collagen fiber deposition, and down-regulated collagen I (Col I) and transforming growth factor-β1 (TGF-β1) expression. In conclusion, the micro-needle designed in this study has great prospects in the treatment of HS.

Synergistic effects of NO/H2S gases on antibacterial, anti-inflammatory, and analgesic properties in oral ulcers using a gas-releasing nanoplatform.

Oral mucosal wounds are more prone to inflammation due to direct exposure to various microorganisms. This can result in pain, delayed healing, and other complications, affecting patients' daily activities such as eating and speaking. Consequently, the overall quality of life for patients is significantly reduced. To address these challenges, we developed a multifunctional therapeutic nanoplatform, DATS@Arg-EA-SA, through the self-assembly of guanidinated dendritic peptides (Arg-EA-SA) that encapsulate diallyl trisulfide (DATS), a hydrogen sulfide (H2S) donor. The guanidine-rich surface of DATS@Arg-EA-SA efficiently neutralizes reactive oxygen species (ROS) in the ulcer microenvironment, generating nitric oxide (NO), which acts as the primary antimicrobial agent by disrupting bacterial membranes. Concurrently, the presence of glutathione triggers the release of H2S from DATS, providing supplementary antibacterial support. DATS@Arg-EA-SA effectively kills all bacteria, achieving results comparable to those of penicillin, a classical antibiotic. Moreover, it demonstrates superior sterilization efficacy against drug-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), significantly outperforming penicillin. Following the initial antimicrobial phase, the nanoplatform transitions into an anti-inflammatory stage. H2S, in synergy with NO, facilitates the conversion of M1 macrophages to M2 macrophages, thereby reducing the expression of inflammatory factors. Importantly, the combination of H2S and NO provides effective analgesia by downregulating the expression of TRPV1 and TRPV4, thus restoring normal dietary behaviors and improving the overall quality of life. This system ultimately promotes collagen fiber deposition and accelerates the re-epithelialization of the ulcer wound, positioning DATS@Arg-EA-SA as a promising gas-delivery nanoplatform for rapid wound repair in the clinical treatment. STATEMENT OF SIGNIFICANCE: Oral mucosal wounds are highly susceptible to microbial infections, leading to inflammation, pain, delayed healing, and a significant decline in quality of life. We developed a multifunctional therapeutic nanoplatform (DATS@Arg-EA-SA) via the self-assembly of guanidinated dendritic peptides encapsulating the H2S donor DATS, which exhibited antibacterial, anti-inflammatory, and analgesic properties. In the oral ulcer microenvironment, DATS@Arg-EA-SA generates substantial NO under elevated ROS levels, while glutathione triggers the controlled release of H2S. NO disrupts bacterial membranes as the primary antibacterial agent, with H2S providing synergistic antibacterial effects. Furthermore, H2S and NO synergistically promote the transformation of M1 to M2 macrophages, attenuating inflammation. Importantly, the combined action of H2S and NO alleviates pain by downregulating TRPV1 and TRPV4, supporting the restoration of normal dietary behavior and improving quality of life.

Using platelet concentrates to treat maxillofacial tissue lesions.

Platelet concentrates (PCs), which are blood products that are abundant in platelets and growth factors, have become pivotal in treating maxillofacial tissue lesions due to their capacity for promoting bone and soft tissue recovery. This review will provide some recent progress of the use of platelet concentrates to treat lesions on maxillofacial tissues. We reviewed the mechanisms by which PCs promote wound healing and tissue recovery and summarized the application of PCs in the treatment of lesions on maxillofacial tissues, including medication-related osteonecrosis of the jaw, post-extraction wound healing, implant surgery, temporomandibular joint diseases, and periodontal tissue restoration. PC promotes the attachment and proliferation of osteoblasts, as well as the synthesis and deposition of collagen fibers by stimulating the AFK pathway and releasing growth factors and cytokines, such as secreting GFs, VEGF, TGF-β, etc. They also induce angiogenesis, inhibit bone resorption, promote the healing of soft tissues, relieve symptoms, reduce postoperative complications and maintain implant stability. PCs may be used as an adjuvant therapy in the treatment of lesions on maxillofacial tissues. However, more studies should refine the preparation and treatment methods for platelet concentrates and establish a foundation for their extensive application.

Fecal Microbiota Transplantation Alleviates Airway Inflammation in Asthmatic Rats by Increasing the Level of Short-Chain Fatty Acids in the Intestine.

Asthma is a prevalent chronic inflammatory disorder of the respiratory tract that not only manifests with respiratory symptoms but also often involves intestinal flora disorders and gastrointestinal dysfunction. Recent studies have confirmed the close relationship between the gut and lungs, known as the "gut-lung axis" theory. Fecal microbiota transplantation (FMT), a method for restoring normal intestinal flora, has shown promise in treating common gastrointestinal diseases. The "gut-lung axis" theory suggests that FMT may have significant therapeutic potential for asthma. In this study, we established an Ovalbumin (OVA)-induced rat model of asthma to investigate the protective effect of FMT on airway inflammation and the restoration of intestinal short-chain fatty acids (SCFAs), aiming to explore its underlying mechanism. Rats in the Control group underwent fecal treatment via gavage (Control-FMT, C-FMT group), while rats in the Asthma group underwent fecal treatment via gavage after asthma induction (Asthma-FMT, A-FMT group). Following a two-week period of continuous intragastric administration, various measurements were conducted to assess pulmonary function, peripheral blood neutrophil, lymphocyte, and eosinophil content, lung tissue pathology, and collagen fiber deposition in the lungs. Additionally, neutrophil and eosinophil content in bronchoalveolar lavage fluid (BALF), expression levels of Interleukin-4 (IL-4), IL-5, IL-13, IL-17, IL-33, leukotrienes (LT), thymic stromal lymphopoietin (TSLP), prostaglandin D2 (PGD2) protein and mRNA in lung tissue, and SCFAs content in stool were evaluated. In the C-FMT group, lung function significantly improved, inflammatory cell content in peripheral blood and BALF decreased, lung tissue pathology and collagen fiber deposition significantly improved, the protein and mRNA levels of lung inflammatory factors IL-4, IL-5, IL-13, IL-17, IL-33, LT, TSLP, PGD2 were significantly decreased, and SCFAs such as acetate (C2), propionate (C3), butyrate (C4), isobutyric acid (I-C4), valeric acid (C5), and isovaleric acid (I-C5) content in stool significantly increased. However, the indexes in the A-FMT group did not show significant recovery, and the treatment effect on asthma symptoms in rats was inferior to that in the C-FMT group. Asthma induced intestinal flora disorders in rats, and FMT treatment improved the inflammatory response in asthmatic rat models and corrected their intestinal SCFAs disorders. Encouraging the recovery of intestinal SCFAs may play a significant role, and beneficial bacteria present in feces may improve asthma symptoms by promoting the remodeling of intestinal flora. This experiment provides further scientific evidence supporting the "gut-lung axis" theory.

Dihydrotanshinone I improves cardiac function by promoting lymphangiogenesis after myocardial ischemia-reperfusion injury.

Dihydrotanshinone I (DHT) is an active ingredient derived from Salvia miltiorrhiza. Previous studies have demonstrated that DHT can improve cardiac function in rats with myocardial ischemia-reperfusion injury (IR). However, the mechanism by which DHT improves myocardial injury in rats still requires further research. Lymphangiogenesis can reduce myocardial edema, inflammation, and fibrosis after myocardial infarction in rats, and improve cardiac function. In this study, the changes in cardiac functions, collagen fiber deposition in the infarcted area and the level of relevant indicators of lymphangiogenesis were examined by echocardiography, Masson's trichrome staining, immunohistochemistry and Western blot, respectively. Human lymphatic endothelial cells (HLECs) were transfected with siVE-cadherin and siVEGFR-3, and the effects of DHT on HLEC cell viability, migration and tube formation were detected through CCK8, TUNEL, transwell, wound healing and tube formation assay. We found that in myocardial IR rats treated with DHT, the levels of LYVE-1, PROX1, VEGF-C, VEGFR-3, IGF-1, podoplanin and IGF-1R, which are associated with lymphangiogenesis, were increased, as well as the level of VE-cadherin, which maintains endothelial cell function. DHT reduced the levels of inflammatory factors and myocardial cell apoptosis, thereby improving cardiac function after I/R. To explore the mechanism of DHT promoting lymphangiogenesis, H2O2 and OGD/R injury models of HLECs were constructed to simulate the microenvironment of myocardial IR in vitro. The results proved that DHT could reduce the damage and apoptosis of HLECs. On the other hand, DHT enhanced the expression of VEGFR-3 and VE-cadherin in HLECs, promoted cell migration and tube formation. The effects of DHT on the tube formation and migration of HLECs were significantly decreased after knocking down VEGFR-3 or VE-cadherin. Our research proposed that DHT could improve the heart function after IR through the enhancement of lymphangiogenesis and contributed to the development of the treatment methods for myocardial IR.

Double-alternating injectable multifunctional hydrogel based on chitosan for skin wound repair.

Injectable hydrogels can be suitable for any irregular wounds to play an important role in wound healing, which have attracted much attention from researchers. Here, a chitosan-based double alternating injectable hydrogel had been proposed, which aligned with characteristics of wound healing. First of all, carboxymethyl chitosan (CMCS) and oxidized gellant (OGG) were used to fabricate above double-alternating injectable hydrogel skeleton (COG) through Schiff base bond. Then, dipotassium glycyrrhizinate (DPG) and bioactive glass (BG) were loaded respectively into COG, forming COG2-D10 and COG2-B0.5 hydrogel. Various properties of above hydrogels such as rheological behaviors, injectable capability, cytocompatibility, antibacterial and anti-inflammatory activity were systematically investigated. The results indicated that above hydrogel not only had a stable network structure, good toughness, injectability, and excellent adhesive properties, but also exhibited efficient antibacterial, anti-inflammatory, hemostatic, and biocompatible properties. The investigation of in vivo full-thickness skin wound healing showed that compared with COG2-D10 or COG2-B0.5 hydrogel alone, the double-alternating COG2-D10/COG2-B0.5 hydrogel could better enhance the efficacy of drugs, promote cell migration and proliferation, accelerate collagen fiber deposition and neovascularization, and significantly improve wound healing (p < 0.01). Therefore, the double-alternating therapy strategy of hydrogel will provide a new approach for the clinical treatment of skin wound healing.

CaGA nanozymes with multienzyme activity realize multifunctional repair of acute wounds by alleviating oxidative stress and inhibiting cell apoptosis.

Acute wounds result from damage to the skin barrier, exposing underlying tissues and increasing susceptibility to bacterial and other pathogen infections. Improper wound care increases the risk of exposure and infection, often leading to chronic nonhealing wounds, which cause significant patient suffering. Early wound repair can effectively prevent the development of chronic nonhealing wounds. In this study, Ca-Gallic Acid (CaGA) nanozymes with multienzyme catalytic activity were constructed for treating acute wounds by coordinating Ca ions with gallic acid. CaGA nanozymes exhibit high superoxide dismutase/catalase (SOD/CAT) catalytic activity and good antioxidant performance in vitro. In vitro experiments demonstrated that CaGA nanozymes can effectively promote cell migration, efficiently scavenge ROS, maintain mitochondrial homeostasis, reduce inflammation, and decrease cell apoptosis. In vivo, CaGA nanozymes promoted granulation tissue formation, accelerated collagen fiber deposition, and reconstructed skin appendages, thereby accelerating acute wound healing. CaGA nanozymes have potential clinical application value in wound healing treatment.

Lung dECM matrikine-based hydrogel reverses bleomycin-induced pulmonary fibrosis by suppressing M2 macrophage polarization

Background.Recent studies have shown promising results using decellularized extracellular matrix (dECM) matrikines-based hydrogel as attractive strategies for preventing and alleviating fibrosis.Methods & Results.Porcine lung decellularization and pepsin digestion were used to prepare the lung dECM hydrogel. Proteomic analysis revealed that the lung dECM hydrogel was enriched in glycoproteins, collagens, laminins, fibrinogen, held receptors, and bound growth factors. With porous structures and good mechanical properties and stability, the lung dECM hydrogel showed low cytotoxicity and good biocompatibility bothin vitroandin vivo. The lung dECM hydrogel was further administered to verify the safety and effectiveness of reversing pulmonary fibrosis in a bleomycin induced rat model. The results revealed a relatively complete alveolar structure with less inflammatory infiltration and a reduced amount of collagen fiber deposition. TMT quantification proteomic analyses revealed significant downregulation of proteins, pathways, and interactions involved in the regulation of ECM components, tissue remodeling, inflammation, and the cytoskeleton and indicated that fibrosis-related proteins were obviously downregulated and inflammation-related proteins were significantly changed, particularly in macrophages, after administration of the lung dECM hydrogel. Opal multiplex immunohistochemistry (mIHC) staining of lung tissue revealed that the inflammatory response was regulated by the lung dECM hydrogel, as indicated by a decrease in the number of CD3+ T cells and macrophages and the suppression of M2 macrophage polarization. Gene set enrichment analysis revealed that downregulated ficolin signaling was enriched in macrophages after lung dECM hydrogel administration, and the findings were verified in lung tissue by mIHC. Additionally, the effects of ficolin B proteins on macrophage polarization were provedin vitro. Conclusion.This study suggested that the lung dECM hydrogel can reverse pulmonary fibrosis by suppressing M2 macrophage polarization through downregulation of the ficolin signaling pathway. Thus, the dECM hydrogel represent a promising class of biological materials for use in regenerative medicine.

Alogliptin attenuates testicular damage induced by monosodium glutamate in both juvenile and adult male rats by activating autophagy: ROS dependent AMPK/mTOR.

Monosodium glutamate (MSG) is one of the most commonly used food additives, known for its adverse health effects. Alogliptin (ALO) is a highly selective dipeptidyl peptidase-4 inhibitor, but its role in male reproductive function remains debated. The study was designed to evaluate and compare the potential of ALO in mitigating MSG-induced testicular toxicity in juvenile and adult male rats. Juvenile and adult male rats were treated with either MSG or pretreated with ALO before MSG administration. The rats then received ALO and MSG concurrently for 28 days. Testicular tissues were isolated and subjected to histo-biochemical and molecular assessments. Our results demonstrated that ALO reversed MSG-induced testicular injury, as evidenced by the restoration of reproductive hormone balance (increased serum luteinizing hormone and testosterone concentrations), suppression of oxidative stress injury (decreased testicular malondialdehyde, increased superoxide dismutase activity, and minimal 8-hydroxy-2'-deoxyguanosine immunoreactivity), inflammation (reduced testicular tumor necrosis factor-alpha levels), and fibrosis (decreased testicular collagen fiber deposition). Additionally, ALO impeded apoptosis and activated autophagy by decreasing caspase-3 activity, stimulating the AMPK/mTOR pathway, downregulating Bax and SQSTM-1/p62 expression, upregulating Bcl2 and Beclin 1, promoting testicular proliferation (increased number of proliferating cell nuclear antigen-positive cells in the testis), restoring glycogen content in the testis (mild to moderate periodic acid-Schiff reaction), and preserving testicular architecture. MSG induced more severe adverse testicular effects in juvenile rats, while ALO pretreatment was more protective in adult rats. ALO's anti-inflammatory, antioxidant, antiapoptotic, pro-autophagic, antifibrotic, and proliferative actions in the testis suggest its promising potential for combating male reproductive dysfunction.

Near-Field Direct Write Electrospinning of PET-Carbon Quantum Dot Solutions.

Electrospinning of polymer material has gained a lot of interest in the past decades. Various methods of electrospinning have been applied for different applications, from needle electrospinning to needleless electrospinning. A relatively new variation of electrospinning, namely near-field electrospinning, has been used to generate well-defined patterns. This variation of electrospinning, also known as near-field direct-write electrospinning, allows for precise control of the fiber deposition, sacrificing on the thickness of the resulting fibers. Typically, for this method, melt electrospinning is preferred, since it provides a higher viscosity of the polymer and thereby better control of the fiber deposition. However, when mixing additives into the spinning dope, a solution spinning approach is preferable since it provides a more homogeneous distribution of the additives in the spinning dope. A fluorescent spinning dope of dissolved PET with fluorescent carbon quantum dots has been used to generate the fluorescent patterns. These can be used to generate logos, bar codes, or QR codes to encode information about the material, such as watermarks or counterfeiting tags.

Development of a spontaneous model of renal interstitial fibrosis in NOD/SCID mice: Aging-induced pathogenesis.

Renal interstitial fibrosis, a condition prevalent in aging humans and animals, is closely linked to the eventual development of renal failure. Establishing an animal model that exactly replicates the pathogenesis of renal interstitial fibrosis induced by natural aging in humans is crucial for advancing mechanistic studies and testing antifibrotic therapies. Implanted allogeneic or xenogeneic cells are cleared by the immune system when stem cell therapy is applied in nonimmunodeficient animal fibrosis models, affecting the effect of the intervention and making it difficult to demonstrate the survival, proliferation, differentiation, or secretion of the delivered autologous human-derived cells. This study effectively developed a model of spontaneous renal interstitial fibrosis linked to natural aging in 43-week-old NOD/SCID mice. Compared with those of 12- and 32-week-old mice, the kidneys of the model mice exhibited prominent fibrosis characteristics, accompanied by numerous fibrous septa and collagen deposition, increased COL1A1 expression, and decreased MMP9 expression. SA-β-gal activity and P21 gene expression levels increased, confirming renal cell senescence in the model mice. Additionally, an increase in α-SMA staining indicated an increase in epithelial-mesenchymal transition. More importantly, we observed TGF-β-SMAD3 pathway activation, mitochondrial dysfunction, decreased antioxidant capacity, oxidative stress, and an enhanced inflammatory response in the model group, consistent with renal interstitial fibrosis in elderly individuals. In this comprehensive investigation, we successfully developed a spontaneous mouse model of renal interstitial fibrosis and revealed the molecular pathways contributing to increased susceptibility to kidney injury and renal fibrosis in elderly individuals.