Effect of Matrix Metalloproteinase 23 Accelerating Wound Healing Induced by Hydroxybutyl Chitosan.

Skin wounds may cause severe financial and social burden due to the difficulties in wound healing. Original inert dressings cannot meet multiple needs in the process of wound healing. Therefore, the development of materials to accelerate healing progress is essential and urgent. In the previous study, we found that the homogeneously synthesized hydroxybutyl chitosan (HBCS) had an effective performance in promoting wound healing. Proteomic analysis of the same specimen suggested that matrix metalloproteinase 23 (MMP23) may play a key role in HBCS expediting the progress of wound healing. In this work, we aim to reveal the underlying mechanism of MMP23 in the dynamic process of cutaneous proliferation and repair period. In order to regulate the expression level of MMP23 in the local wound area, we leaded in adeno-associated virus (AAV) to specifically decreased expression quantity of MMP23 in rat skin. In contrast to the negative control groups, we found that the wound closed faster and the collagen fibers and neovascularization were significantly increased in AAV groups. These findings highlighted that MMP23 was involved in wound healing after traumatic injury, and managing the expression of MMP23 could be a potential intervention target to accelerate wound healing.

Biocompatible, antibacterial and anti-inflammatory zinc ion cross-linked quaternized cellulose­sodium alginate composite sponges for accelerated wound healing.

Bacterial infection has become one of the most challenges for wound healing, which causes serious inflammatory response and delays the healing process. Herein, a novel sponge with excellent biocompatible, antibacterial and anti-inflammatory properties based on quaternized cellulose (QC), sodium alginate (SA) and Zn2+ was reported. The existence of physical interactions, such as electrostatic interaction, chelation and hydrogen bonding endowed the sponges with enhanced mechanical property. The composite sponges exhibited outstanding biocompatibility and hemostatic efficiency due to the compatible nature of the component and physical cross-linking, as well as superior antibacterial property benefited from the synergistic effects of steady Zn2+ release and quaternary ammonium group. In vivo investigation validated that the enhanced antibacterial and anti-inflammatory effect of the sponges, which significantly promoted wound closure and the reconstruction of skin tissue through epithelial regeneration, collagen deposition and mitigating inflammatory cell infiltration. Overall, the novel sponge demonstrated great potentials in bacteria-associated wound management.

Hypothermic oxygenated perfusion inhibits HECTD3-mediated TRAF3 polyubiquitination to alleviate DCD liver ischemia-reperfusion injury.

Ischemia-reperfusion injury (IRI) is an inevitable and serious clinical problem in donations after heart death (DCD) liver transplantation. Excessive sterile inflammation plays a fateful role in liver IRI. Hypothermic oxygenated perfusion (HOPE), as an emerging organ preservation technology, has a better preservation effect than cold storage (CS) for reducing liver IRI, in which regulating inflammation is one of the main mechanisms. HECTD3, a new E3 ubiquitin ligase, and TRAF3 have an essential role in inflammation. However, little is known about HECTD3 and TRAF3 in HOPE-regulated liver IRI. Here, we aimed to investigate the effects of HOPE on liver IRI in a DCD rat model and explore the roles of HECTD3 and TRAF3 in its pathogenesis. We found that HOPE significantly improved liver damage, including hepatocyte and liver sinusoidal endothelial cell injury, and reduced DCD liver inflammation. Mechanistically, both the DOC and HECT domains of HECTD3 directly interacted with TRAF3, and the catalytic Cys (C832) in the HECT domain promoted the K63-linked polyubiquitination of TRAF3 at Lys138. Further, the ubiquitinated TRAF3 at Lys138 increased oxidative stress and activated the NF-κB inflammation pathway to induce liver IRI in BRL-3A cells under hypoxia/reoxygenation conditions. Finally, we confirmed that the expression of HECTD3 and TRAF3 was obviously increased in human DCD liver transplantation specimens. Overall, these findings demonstrated that HOPE can protect against DCD liver transplantation-induced-liver IRI by reducing inflammation via HECTD3-mediated TRAF3 K63-linked polyubiquitination. Therefore, HOPE regulating the HECTD3/TRAF3 pathway is a novel target for improving IRI in DCD liver transplantation.

Clinical characteristics and immunosuppressant management of coronavirus disease 2019 in solid organ transplant recipients.

Over 1 000 000 cases of coronavirus disease 2019 (COVID-19) have been confirmed since the worldwide outbreak began. Not enough data on infected solid organ transplant (SOT) recipients are available, especially data about the management of immunosuppressants. We report two cases of COVID-19 in two transplant recipients, with different treatments and prognoses. The first patient received liver transplantation due to hepatitis B virus-related hepatocellular carcinoma and was confirmed to have COVID-19 9 days later. Following a treatment regimen consisting of discontinued immunosuppressant use and low-dose methylprednisolone-based therapy, the patient developed acute rejection but eventually recovered. The other patient had undergone a renal transplant from a living-related donor 17 years ago, and was admitted to the hospital because of persistent fever. This patient was also diagnosed with COVID-19. His treatment regimen consisted of reduced immunosuppressant use. No signs of rejection were observed during the regimen. In the end, the patient successfully recovered from COVID-19. These effectively treated cases can provide a basis for immunosuppressant management of COVID-19-positive SOT recipients.

Vagus Nerve Stimulation Alleviates Hepatic Ischemia and Reperfusion Injury by Regulating Glutathione Production and Transformation.

Inflammation and oxidative stress are pivotal mechanisms for the pathogenesis of ischemia and reperfusion injury (IRI). Vagus nerve stimulation (VNS) may participate in maintaining oxidative homeostasis and response to external stimulus or injury. We investigated whether the in vivo VNS can protect the liver from IRI. In this study, hepatic IRI were induced by ligating the vessels supplying the left and middle lobes of the liver, which underwent 1 h occlusion followed with 24 h reperfusion. VNS was initiated 15 min after ischemia and continued 30 min. Hepatic function, histology, and apoptosis rates were evaluated after 24 h reperfusion. Compared with the IRI group, VNS significantly improved hepatic function. The protective effect was accompanied by a reduction in histological damage in the ischemic area, and the apoptosis rate of hepatocytes has considerable reduction. To find the underlying mechanism, proteomic analysis was performed and differential expression of glutathione synthetase (GSS) and glutathione S-transferase (GST) was observed. Subsequently, test results indicated that VNS upregulated the expression of mRNA and protein of GSS and GST. Meanwhile, VNS increased the plasma levels of glutathione and glutathione peroxidases. We found that VNS alleviated hepatic IRI by upregulating the antioxidant glutathione via the GSS/glutathione/GST signaling pathway.

Construction of cellulose nanofibers/quaternized chitin/organic rectorite composites and their application as wound dressing materials.

Traumatic injury is a major cause of mortality, and poor wound healing affects millions of people. Thus, the development of effective wound dressings is essential for speeding up wound healing and decreasing mortality. In this study, a suspension of carboxylated brown algae cellulose nanofibers (BACNFs) with a high aspect ratio was freeze dried to prepare a sponge. The sponge showed high porosity and water absorption capacity; thus, it can absorb wound exudates when used as a wound dressing. In addition, quaternized ß-chitin (QC) with antibacterial properties was intercalated into the interlayer space of the organic rectorite (OREC) via electrostatic interactions to obtain composite suspensions (QCRs) with improved antimicrobial activity compared to that of QC alone. Subsequently, the BACNF sponge was soaked in the QCR suspension to absorb QCRs via electrostatic interactions and hydrogen bonding from which cellulose nanofiber/quaternized chitin/organic rectorite composite (BACNF/QCR) sponges were constructed via freeze-drying. The in vivo animal tests demonstrated that the BACNF/QCR sponges rapidly induced hemostasis in a rat tail amputation test, making them superior to the traditional hemostatic materials. Furthermore, BACNFs/QCRs could substantially promote collagen synthesis and neovascularization, thereby accelerating wound healing 3 days earlier than gauze. This multi-functional biomedical material, fabricated using natural substances, shows great potential to be used for wound healing.

Homogeneously Synthesized Hydroxybutyl Chitosans in Alkali/Urea Aqueous Solutions as Potential Wound Dressings.

Wound healing is a clinical challenge, and nontoxic, nonadherent wound dressings that promote healing are urgently needed. Herein, hydroxybutyl chitosans (HBCSs) with the degree of substitution (DS) from 0.41 to 1.38 were synthesized in alkali/urea aqueous solutions, from which sponge-like dressings were prepared by freeze-drying. The pore size of the sponges was in the range of 14.8-18.4 µm, and the porosity was about 98-99%. The compressive strength of the sponges decreased with increasing DS of HBCS. Cytocompatibility studies with normal human dermal fibroblast (NHDF) cells demonstrated that HBCSs were nontoxic and could even promote the growth of fibroblasts. Further tests revealed that HBCS-3 (DS = 0.85) and HBCS-5 (DS = 1.38) exhibited better hemocompatibility and a low blood-clotting index (BCI). Therefore, these two samples were selected as model dressings for in vivo wound-healing assessment in rats. The experiments suggested that HBCS-3 significantly shortened the wound recovery period compared with HBCS-5, chitosan, and gauze by facilitating epithelialization, collagen deposition, and neovascularization and activating the immune system. The results highlighted the potential of HBCSs as efficient dressings for promoting wound healing.

Polyaniline promotes peripheral nerve regeneration by enhancement of the brain­derived neurotrophic factor and ciliary neurotrophic factor expression and activation of the ERK1/2/MAPK signaling pathway.

A previous study has demonstrated a progression in the nerve regeneration by polyaniline/cellulose (PANI/RC), although the underlying mechanism was not elucidated. In the present study, regenerated nerves were investigated, using histological techniques, functional assays and western blot analysis. The triceps surae muscle weight ratio percentages of the sham, regenerated cellulose (RC) and the PANI/RC groups were 38.88±4.76 and 76.32±7.11%, respectively. The thickness of the myelin sheath for the aforementioned groups were as follows: 1.2±0.27; 0.49±0.21 and 0.93±0.28 µl. Western blot analysis demonstrated that the ciliary neurotrophic factor (CNTF) and brain­derived neurotrophic factor (BDNF) were highly expressed in the regenerated nerve in the presence of polyaniline. Phosphorylated extracellular kinase (p­ERK)1/2 expression in the PANI/RC group was significantly elevated compared with the RC group (1.83­fold) and the sham group (4.92­fold). The expression of the axon sprout­associated proteins, such as Tau, α­tubulin and growth associated protein­43, were increased (1.64, 1.59 and 1.24­fold, respectively) compared with the RC group. The results demonstrated that PANI enhances the expression and secretion of BDNF and CNTF, activates the ERK1/2 signaling pathway and increases the expression levels of the GAP­43, Tau and α­tubulin, suggesting an insight into nerve regeneration and possible clinical interventions in nerve injury.