ABSTRACT
Chitin and its deacetylated form, chitosan, have demonstrated remarkable versatility in the realm of biomaterials. Their exceptional biocompatibility, antibacterial properties, pro- and anticoagulant characteristics, robust antioxidant capacity, and anti-inflammatory potential make them highly sought-after in various applications. This review delves into the mechanisms underlying chitin/chitosan's biological activity and provides a comprehensive overview of their derivatives in fields such as tissue engineering, hemostasis, wound healing, drug delivery, and hemoperfusion. However, despite the wealth of studies on chitin/chitosan, there exists a notable trend of homogeneity in research, which could hinder the comprehensive development of these biomaterials. This review, taking a clinician's perspective, identifies current research gaps and medical challenges yet to be addressed, aiming to pave the way for a more sustainable future in chitin/chitosan research and application.
Subject(s)
Biocompatible Materials , Chitin , Chitosan , Tissue Engineering , Chitosan/chemistry , Chitosan/pharmacology , Chitin/chemistry , Humans , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Animals , Tissue Engineering/methods , Wound Healing/drug effects , Drug Delivery Systems , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Hemostasis/drug effectsABSTRACT
Injectable hydrogels fabricated from natural polymers have attracted increasing attentions for their potential in biomedical application owing to the biocompatibility and biodegradability. A new class of natural polymer based self-healing hydrogel is constructed through dynamic covalent bonds. The injectable self-healing hydrogels are fabricated by introducing alginate aldehyde to form Schiff base bonds with the chitin nanofibers. These hydrogels demonstrate excellent self-healing properties, injectability, and pH-responsive sol-gel transition behaviors. As a result, they can serve as carriers to allow an effective encapsulation of doxorubicin (DOX) for drug delivery. Furthermore, these hydrogels exhibit excellent biocompatibility and degradability in vitro and in vivo. The sustained release of DOX from the hydrogels effectively suppresses tumor growth in animal models without causing significant systemic toxicity, suggesting their potential application in anti-tumor therapies.
Subject(s)
Alginates , Antineoplastic Agents , Chitin , Doxorubicin , Hydrogels , Nanofibers , Chitin/chemistry , Chitin/analogs & derivatives , Alginates/chemistry , Nanofibers/chemistry , Animals , Doxorubicin/chemistry , Doxorubicin/pharmacology , Hydrogels/chemistry , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Humans , Mice , Drug Delivery Systems , Drug Carriers/chemistry , Drug Liberation , Biocompatible Materials/chemistry , Injections , Cell Line, TumorABSTRACT
Hepatectomy, a surgical procedure for liver cancer, is often plagued by high recurrence rates worldwide. The recurrence of liver cancer is primarily attributed to microlesions in the liver, changes in the immune microenvironment, and circulating tumor cells in the bloodstream. To address this issue, a novel intervention method that combines intraoperative hemostasis with mild photothermal therapy is proposed, which has the potential to ablate microlesions and improve the immune microenvironment simultaneously. Specifically, the integrated strategy is realized based on the fibrous chitosan/polydopamine sponge (CPDS), which is constructed from shearing-flow-induced oriented hybrid chitosan fibers and subsequent self-assembly of polydopamine. The CPDS demonstrates high elasticity, excellent water absorption, and photothermal conversion performance. The results confirm the efficient hemostatic properties of the fibrous CPDS in various bleeding models. Notably, in subcutaneous and orthotopic postoperative recurrence and metastasis models of hepatocellular carcinoma, the fibrous CPDS significantly inhibits local tumor recurrence and distant metastasis. Moreover, the combination with lenvatinib can substantially enhance the antitumor effect. This comprehensive treatment strategy offers new insights into hepatectomy of liver cancer, representing a promising approach for clinical management.
Subject(s)
Carcinoma, Hepatocellular , Chitosan , Indoles , Liver Neoplasms , Polymers , Humans , Carcinoma, Hepatocellular/surgery , Liver Neoplasms/surgery , Chitosan/pharmacology , Neoplasm Recurrence, Local/prevention & control , Hemostasis , Tumor MicroenvironmentABSTRACT
Reprogramming of lipid metabolism during hepatocarcinogenesis is not well elucidated. Here, we aimed to explore pivotal RNA-binding motif proteins (RBMs) in lipid metabolism and their therapeutic potential in hepatocellular carcinoma (HCC). Through bioinformatic analysis, we identified RBM45 as a critical gene of interest among differentially expressed RBMs in HCC, with significant prognostic relevance. RBM45 influenced the malignant biological phenotype and lipid metabolism of HCC cells. Mechanically, RBM45 promotes de novo lipogenesis in HCC by directly targeting two key enzymes involved in long-chain fatty acid synthesis, ACSL1 and ACSL4. RBM45 also targets Rictor, which has been demonstrated to modulate lipid metabolism profoundly. RBM45 also aided lipid degradation through activating a key fatty acid ß oxidation enzyme, CPT1A. Thus, RBM45 boosted lipid synthesis and decomposition, indicating an enhanced utility of lipid fuels in HCC. Clinically, body mass index was positively correlated with RBM45 in human HCCs. The combination of a PI3K/AKT/mTOR pathway inhibitor in vitro or Sorafenib in orthotopic liver cancer mouse models with shRBM45 has a more significant therapeutic effect on liver cancer than the drug alone. In summary, our findings highlight the versatile roles of RBM45 in lipid metabolism reprogramming and its therapeutic potential in HCC. Lipids induced RBM45 expression. In turn, RBM45 promoted the utility of lipid in HCCs through accelerating both de novo lipogenesis and fatty acid ß oxidation, which required the participation of Rictor, a core component of mTORC2 that has been demonstrated to modulate lipid metabolism potently, as well as ACSL1/ACSL4, two key enzymes of long-chain fatty acid synthesis. When the first-line chemotherapy drug sorafenib is combined with a PI3K/AKT/mTOR pathway inhibitor (MK2206 is an AKT inhibitor, rapamycin is a mTOR inhibitor, and inhibiting RBM45 can significantly inhibit Rictor), cell cycle, proliferation, lipid metabolism reprogramming, and hepatocarcinogenesis can be significantly inhibited, while apoptosis can be significantly enhanced.
Subject(s)
Carcinoma, Hepatocellular , Coenzyme A Ligases , Liver Neoplasms , Nerve Tissue Proteins , RNA-Binding Proteins , Mice , Animals , Humans , Carcinoma, Hepatocellular/pathology , Liver Neoplasms/pathology , Lipid Metabolism/genetics , Sorafenib/pharmacology , Sorafenib/therapeutic use , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/genetics , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction/genetics , Cell Line, Tumor , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolism , Transcription Factors/metabolism , Protein Kinase Inhibitors/pharmacology , Phosphoinositide-3 Kinase Inhibitors/pharmacology , Lipids , Fatty Acids , Cell Proliferation/geneticsABSTRACT
Aldehyde dehydrogenase 2 (ALDH2), an acetaldehyde dehydrogenase in mitochondria, is primarily responsible for metabolizing alcohol-derived acetaldehyde and other endogenous aldehydes. Inactivating ALDH2 rs671 polymorphism is found in up to 8 % of the global population and 40 % of the East Asian population. Recent studies have shown that rs671 SNP mutation in the human ALDH2 gene is associated with an increased risk of metabolic dysfunction-associated steatotic liver diseases (MASLD), but the mechanism remains unclear. Here, we identify the role of ALDH2 in MASLD. Firstly, ALDH2 activity was lower in MASLD patients and the methionine-choline deficiency (MCD) diet induced MASLD model. Secondly, activation of ALDH2 activity with Alda-1 (ALDH2 agonist) attenuated MCD-diet induced hepatic triglyceride (TG) accumulation and steatosis, whereas the opposite result was observed with cyanamide (CYA, ALDH2 inhibitor). Furthermore, ALDH2 deficiency exacerbated hepatic steatosis, inflammation, and fibrosis in the MCD-diet induced mice. RNA sequencing (RNA-seq) revealed that oxysterol 7-α hydroxylase (Cyp7b1) and the related metabolic pathway significantly changed in the MCD-diet challenged ALDH2-/- mice. In ALDH2-/- mice, the expression of Cyp7b1 was downregulated and FXR/SHP signaling was inhibited, reducing the alternative bile acid (BA) synthetic pathway. In our in vitro experiments, knockdown of ALDH2 exacerbated TG accumulation in hepatocytes, whereas the opposite result was observed with overexpression of ALDH2. Moreover, chenodeoxycholic acid (CDCA) rescued ALDH2 downregulation induced TG accumulation in hepatocytes. Our study reveals that ALDH2 attenuates hepatocyte steatosis by regulating the alternative BA synthesis pathway, and ALDH2 may serve as a potential target for the treatment of MASLD.
Subject(s)
Choline Deficiency , Fatty Liver , Humans , Mice , Animals , Methionine , Fatty Liver/etiology , Racemethionine , Diet , Bile Acids and Salts , Aldehyde Dehydrogenase, Mitochondrial/genetics , Mice, Inbred C57BLABSTRACT
Hypothermic machine perfusion (HMP) has been demonstrated to be more effective in mitigating ischemia-reperfusion injury (IRI) of donation after circulatory death (DCD) organs than cold storage (CS), yet the underlying mechanism remains obscure. We aimed to propose a novel therapeutic approach to ameliorate IRI in DCD liver transplantation. Twelve clinical liver samples were randomly assigned to HMP or CS treatment and subsequent transcriptomics analysis was performed. By combining in vivo HMP models, we discovered that HMP attenuated inflammation, oxidative stress, and apoptosis in DCD liver through a SEPRINA3-mediated PI3Kδ/AKT signaling cascade. Moreover, in the hypoxia/reoxygenation (H/R) model of BRL-3A, overexpression of SERPINA3 mitigated H/R-induced apoptosis, while SERPINA3 knockdown exacerbated cell injury. Idelalisib (IDE) treatment also reversed the protective effect of SERPINA3 overexpression. Overall, our research provided new insights into therapeutic strategies and identified potential novel molecular targets for therapeutic intervention against DCD liver.
Subject(s)
Liver Transplantation , Reperfusion Injury , Serpins , Humans , Proto-Oncogene Proteins c-akt/metabolism , Liver/metabolism , Perfusion , Reperfusion Injury/prevention & control , Reperfusion Injury/metabolism , Serpins/metabolismABSTRACT
BACKGROUND: Mutations in TP53 gene is considered a main driver of hepatocellular carcinoma (HCC). While TP53 mutations are the leading cause of p53 dysfunction, their occurrence rates may drop to approximately 10% in cohorts without hepatitis B virus and aflatoxin exposure. This observation suggests that the deactivation of wild-type p53 (p53wt) may be a critical factor in the majority of HCC cases. However, the mechanism undermining p53wt activity in the liver remains unclear. METHODS: Microarray analysis and luciferase assay were utilized to confirm target associations. Gain- and/or loss-of-function methods were employed to assess alterations in signaling pathways. Protein interactions were analyzed by molecular immunological methods and further visualized by confocal microscopy. Bioinformatic analysis was performed to analyze clinical significance. Tumor xenograft nude mice were used to validate the findings in vivo. RESULTS: Our study highlights the oncogenic role of Rictor, a key component of the mammalian target of rapamycin complex 2 (mTORC2), in hepatocytes. Rictor exerts its oncogenic function by binding to p53wt and subsequently blocking p53wt activity based on p53 status, requiring the involvement of mTOR. Moreover, we observed a dynamic nucleocytoplasmic distribution pattern of Rictor, characterized by its translocation from the nucleus (in precancerous lesions) to the cytoplasm (in HCCs) during malignant transformation. Notably, Rictor is directly targeted by the liver-enriched microRNA miR-192, and the disruption of the miR-192-Rictor-p53-miR-192 signaling axis was consistently observed in both human and rat HCC models. Clinical analysis associated lower miR-192/higher Rictor with shorter overall survival and more advanced clinical stages (P < 0.05). In mice, xenograft tumors overexpressing miR-192 exhibited lower Rictor expression levels, leading to higher p53 activity, and these tumors displayed slower growth compared to untreated HCC cells. CONCLUSIONS: Rictor dynamically shuttles between the nucleus and cytoplasm during HCC development. Its pivotal oncogenic role involves binding and inhibiting p53wt activity within the nucleus in early hepatocarcinogenesis. Targeting Rictor presents a promising strategy for HCC based on p53 status.
Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , Rapamycin-Insensitive Companion of mTOR Protein , Animals , Humans , Mice , Rats , Carcinogenesis/genetics , Carcinoma, Hepatocellular/pathology , Cell Line, Tumor , Cell Transformation, Neoplastic/genetics , Gene Expression Regulation, Neoplastic , Genes, p53 , Hepatocytes/pathology , Liver Neoplasms/pathology , Mice, Nude , MicroRNAs/metabolism , Tumor Suppressor Protein p53/metabolism , Rapamycin-Insensitive Companion of mTOR Protein/metabolismABSTRACT
OBJECTIVES: Drain tube management after liver transplant is controversial. A new peritoneal drainage management protocol was developed to validate clinical characteristics, such as drain characteristics, postoperative complications, duration of postoperative hospital stay, changes in albumin levels, and 30-day readmission rates. MATERIALS AND METHODS: Data from 183 consecutive patients who underwent deceased donor liver transplant at our institution between January 2019 and June 2022 were retrospectively analyzed. A new drain management protocol was implemented on August 1, 2021, which included early removal of the drain tube when the serum albumin level was >3 g/dL and nonchylous fluid drainage was <200 mL/day. RESULTS: When we compared the traditional and new drain management protocol groups (n = 131 vs n = 52), the new management protocol group showed a decrease in the median duration of intraperitoneal drainage. In addition, the median length of postoperative hospital stay decreased from 33 to 27 days and serum albumin levels returned to normal faster at postoperative 3 weeks. No significant differences were found in postoperative hemorrhage, hematoma, hydrops abdominis, infections, biliary complications, orin the rate ofreinterventions and 30-day rehospitalizations. CONCLUSIONS: The new management protocol was associated with fewer postoperative hospital days and faster recovery than traditional management. Our findings may aid in the development of new drain policy recommendations based on preexisting risk factors.
Subject(s)
Liver Transplantation , Humans , Liver Transplantation/adverse effects , Retrospective Studies , Time Factors , Living Donors , Drainage/adverse effects , Drainage/methods , Postoperative Complications/etiology , Postoperative Complications/therapy , Length of Stay , Serum Albumin , HospitalsABSTRACT
BACKGROUND: Artificial ovary (AO) is an alternative approach to provide physiological hormone to post-menopausal women. The therapeutic effects of AO constructed using alginate (ALG) hydrogels are limited by their low angiogenic potential, rigidity, and non-degradability. To address these limitations, biodegradable chitin-based (CTP) hydrogels that promote cell proliferation and vascularization were synthesized, as supportive matrix. METHODS: In vitro, follicles isolated from 10-12-days-old mice were cultured in 2D, ALG hydrogels, and CTP hydrogels. After 12 days of culture, follicle growth, steroid hormone levels, oocyte meiotic competence, and expression of folliculogenesis-related genes were monitored. Additionally, follicles isolated from 10-12-days-old mice were encapsulated in CTP and ALG hydrogels and transplanted into the peritoneal pockets of ovariectomised (OVX) mice. After transplantation, steroid hormone levels, body weight, rectal temperature, and visceral fat of the mice were monitored every two weeks. At 6 and 10 weeks after transplantation, the uterus, vagina, and femur were collected for histological examination. RESULTS: The follicles developed normally in CTP hydrogels under in vitro culture conditions. Additionally, follicular diametre and survival rate, oestrogen production, and expression of folliculogenesis-related genes were significantly higher than those in ALG hydrogels. After one week of transplantation, the numbers of CD34-positive vessels and Ki-67-positive cells in CTP hydrogels were significantly higher than those in ALG hydrogels (P < 0.05), and the follicle recovery rate was significantly higher in CTP hydrogels (28%) than in ALG hydrogels (17.2%) (P < 0.05). After two weeks of transplantation, OVX mice implanted with CTP grafts exhibited normal steroid hormone levels, which were maintained until week eight. After 10 weeks of transplantation, CTP grafts effectively ameliorated bone loss and atrophy of the reproductive organs, as well as prevented the increase in body weight and rectal temperature in OVX mice, which were superior to those elicited by ALG grafts. CONCLUSIONS: Our study is the first to demonstrate that CTP hydrogels support follicles longer than ALG hydrogels in vitro and in vivo. The results highlight the clinical potential of AO constructed using CTP hydrogels in the treatment of menopausal symptoms.
Subject(s)
Osteoporosis , Ovary , Female , Mice , Animals , Hydrogels/pharmacology , Chitin , Hormones , SteroidsABSTRACT
Permanent hypoparathyroidism is a postoperative complication of thyroid and parathyroid surgery and can be cured by cryopreserved parathyroid autotransplantation (CPAT). However, due to the lack of unified and standardized guidelines, the limited ability of the parathyroid tissue itself to withstand cryopreservation, and some yet-to-be-defined processes or technologies, the success rate of cryopreserved parathyroid autotransplantation varies between institutions; it is low for some institutions and high for others. Due to the sparsity of data, views vary on which factors most influence the success rate of cryopreserved parathyroid autotransplantation. In this review, we analyzed the following probable influencing factors: ischemic period before cryopreservation; processes of cryopreservation and thawing, including freezing medium; freezing and thawing methods; duration of cryopreservation; examination of the graft before transplantation; graft site; mass of transplanted tissue fragments; blood calcium level; and the evaluation criteria for cryopreserved parathyroid autotransplantation success. Although the effects of these factors are debatable, we hypothesized that examining them in the above-given order to determine whether they affect the success rate of cryopreserved parathyroid autotransplantation could be beneficial to maximizing the success rate. Our findings led us to conclude that cryopreserved parathyroid autotransplantation operations should be standardized. Standardized guidelines for cryopreserved parathyroid autotransplantation that include such factors as ischemic period time, freezing and thawing methods, and recipient status should be established based on a comprehensive analysis of these factors.
Subject(s)
Hypoparathyroidism , Parathyroid Glands , Humans , Transplantation, Autologous , Parathyroid Glands/surgery , Cryopreservation , Postoperative ComplicationsABSTRACT
OBJECTIVE: Little is known about the role of microRNA-29a-3p (miR-29a-3p) in inflammation-related pyroptosis, especially in drug-induced acute liver failure (DIALF). This study aimed to identify the relationship between miR-29a-3p and inflammation-related pyroptosis in DIALF and confirm its underlying mechanisms. METHODS: Thioacetamide (TAA)- and acetaminophen (APAP)-induced ALF mouse models were established, and human samples were collected. The expression levels of miR-29a-3p and inflammation and pyroptosis markers were measured by quantitative real-time polymerase chain reaction (qRT-PCR), Western blotting, or immunochemical staining in miR-29a-3p knock-in transgenic mouse (MIR29A(KI/KI)) DIALF models. In addition, RNA sequencing was conducted to explore the mechanisms. RESULTS: MiR-29a-3p levels were decreased in TAA- and APAP-induced DIALF models. MiR-29a-3p prevented DIALF caused by TAA and APAP. RNA sequencing and further experiments showed that the protective effect of miR-29a-3p on DIALF was mainly achieved through inhibition of inflammation-related pyroptosis, and the inhibition was dependent on activation of the PI3K/AKT pathway. In addition, miR-29a-3p levels were reduced, and pyroptosis was activated in both peripheral blood mononuclear cells and liver tissues of DIALF patients. CONCLUSION: The study supports the idea that miR-29a-3p inhibits pyroptosis by activating the PI3K/AKT pathway to prevent DIALF. MiR-29a-3p may be a promising therapeutic target for DIALF.
Subject(s)
Liver Failure, Acute , MicroRNAs , Mice , Animals , Humans , MicroRNAs/genetics , MicroRNAs/metabolism , Pyroptosis/genetics , Proto-Oncogene Proteins c-akt/genetics , Acetaminophen/adverse effects , Leukocytes, Mononuclear/metabolism , Phosphatidylinositol 3-Kinases , Inflammation/chemically induced , Inflammation/genetics , Liver Failure, Acute/chemically induced , Liver Failure, Acute/geneticsABSTRACT
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.
Subject(s)
Chitosan , Wound Healing , Animals , Rats , Chitosan/pharmacology , Proteomics , Skin , Metalloendopeptidases/metabolismABSTRACT
Objective: Ischemia-reperfusion injury (IRI) is an important cause of delayed functional recovery after transplantation. This study is aimed at investigating the molecular mechanism of ALDH2 in a kidney ischemia-reperfusion model based on RNA-seq. Methods: We performed kidney ischemia-reperfusion in ALDH2-/- and WT mice and evaluated kidney function and morphology using SCr, HE staining, TUNEL staining, and TEM. We used RNA-seq to compare mRNA expression in ALDH2-/- and WT mice after IR, and then, we verified the related molecular pathways by PCR and western blotting. In addition, activators and inhibitors of ALDH2 were used to alter the activity of ALDH2. Finally, we established a model of hypoxia and reoxygenation in HK-2 cells and clarified the role of ALDH2 in IR by interfering with ALDH2 and using an NF-κB inhibitor. Results: After kidney ischemia-reperfusion, the SCr value increased significantly, kidney tubular epithelial cells were damaged, and the apoptosis rate increased. In the microstructure, mitochondria were swollen and deformed, and ALDH2 deficiency aggravated these changes. The NF-κB pathway and IL-17 pathway were significantly enriched in ALDH2-/- mice compared with WT mice according to KEGG enrichment analysis of the RNA-seq data. The PCR results showed that the mRNA expression levels of IκBα and IL-17B, C, D, E, and F were significantly higher than those in the WT-IR group. Western blot verification results showed that ALHD2 knockdown resulted in increased phosphorylation of IκBα, increased phosphorylation of NF-κB, and increased expression of IL-17C. When we used ALDH2 agonists, the number of lesions and the expression levels of the corresponding proteins were reduced. Knockdown of ALDH2 in HK-2 cells resulted in a higher proportion of apoptotic cells after hypoxia and reoxygenation, but inhibiting the phosphorylation of NF-κB prevented the increase in apoptosis and reduced the protein expression level of IL-17C. Conclusion: ALDH2 deficiency can lead to the aggravation of kidney ischemia-reperfusion injury. RNA-seq analysis and validation by PCR and western blotting revealed that this effect may be due to the promotion of IκBα/NF-κB p65 phosphorylation during ischemia-reperfusion caused by ALDH2 deficiency, which then leads to an increase in inflammatory factors, including IL-17C. Thus, cell death is promoted, and kidney IRI is eventually aggravated. We link ALDH2 deficiency with inflammation, revealing a new idea for ALDH2-related research.
Subject(s)
Aldehyde Dehydrogenase, Mitochondrial , Kidney , Reperfusion Injury , Animals , Mice , Aldehyde Dehydrogenase, Mitochondrial/genetics , Hypoxia , Interleukin-17 , NF-kappa B , NF-KappaB Inhibitor alpha , RNA, MessengerABSTRACT
Natural polymer hydrogels are widely used in various aspects of biomedical engineering, such as wound repair, owing to their abundance and biosafety. However, the low strength and the lack of function restricted their development and application scope. Herein, we fabricated novel multifunctional chitin/PEGDE-tannic acid (CPT) hydrogels through chemical- and physical-crosslinking strategies, using chitin as the base material, polyethylene glycol diglycidyl ether (PEGDE) and tannic acid (TA) as crosslinking agents, and 90 % ethanol as the regenerative bath. CPT hydrogels maintained a stable three-dimensional porous structure with suitable water contents and excellent biocompatibility. The mechanical properties of hydrogels were greatly improved (tensile stress up to 5.43 ± 1.14 MPa). Moreover, CPT hydrogels had good antibacterial, antioxidant, and hemostatic activities and could substantially promote wound healing in a rat model of full-thickness skin defect by regulating inflammatory responses and promoting collagen deposition and blood vessel formation. Therefore, this work provides a useful strategy to fabricate novel multifunctional CPT hydrogels with excellent mechanical, antibacterial, antioxidant, hemostatic, and biocompatible properties. CPT hydrogels could be promising candidates for wound healing.
Subject(s)
Hemostatics , Rats , Animals , Hemostatics/pharmacology , Antioxidants/pharmacology , Antioxidants/chemistry , Hydrogels/pharmacology , Hydrogels/chemistry , Wound Healing/physiology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Chitin/pharmacologyABSTRACT
Hypothermic machine perfusion (HMP) is a preferable measure to preserve kidneys from donation after cardiac death (DCD), while the current standard perfusate is imperfect. We synthesized amphiphilic chitosan, N-alkylated-O-(2-hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (N-alkyl-O-HTCC) as additive in the perfusate, which can self-assembly into micelles in water (size 133 ± 8.48 nm) (ζ-potential 43.9 ± 2.06 mV), with good antibacterial activity for Escherichia coli and Staphylococcus aureus. The derivates can also deliver hydrophobic drug Alda-1 into kidneys through HMP, with drug loading ratio (~42.14%). The delivery system specifically activated mitochondrial acetaldehyde dehydrogenase 2 in kidneys and reduced the ischemic injury. What's more, the addition of N-alkyl-O-HTCC in HMP also activated mitochondria superoxide dismutase 2, presented nice antioxidant activity. These all helped to improve the quality of DCD kidneys. This study provides a feasible amphiphilic carrier for hydrophobic drugs, and provides efficient guidance for perfusate improvement.
Subject(s)
Chitosan , Nanoparticles , Anti-Bacterial Agents/pharmacology , Antioxidants/pharmacology , Chitosan/pharmacology , Kidney , Organ PreservationABSTRACT
BACKGROUND: The aims of this study were to investigate the pathologic manifestation of pretransplant biopsy and to provide an accurate assessment method for liver graft of China Donation after Citizen's Death (CDCD). METHODS: A retrospective analysis was performed based on clinical and biopsy data of 96 CDCD liver transplantations completed between January 2012 and December 2017. The pretransplant pathologic sections were semiquantitatively scored according to Banff Schema recommendations on liver allograft pathology. Graft overall survival (OS) and early allograft dysfunction (EAD) rates were observed. RESULTS: The histologic analysis of the 96 CDCD liver graft biopsy specimens was summarized, including portal area neutrophilic infiltrate, macrovesicular steatosis, microvesicular steatosis, and hepatocellular swelling. Among these pathologic characteristics, only portal area neutrophilic infiltrate ≥20% was an independent risk factor for graft survival, although it has limited effect on the recipient's short-term prognosis. CONCLUSIONS: We found that portal area neutrophilic infiltrate ≥20% was an independent risk factors for long-term graft survival. According to this criterion, we can identify liver transplant recipients at risk for poor prognosis and make timely interventions.
Subject(s)
Liver Transplantation , Graft Survival , Humans , Liver , Living Donors , Retrospective Studies , Risk Factors , Tissue DonorsABSTRACT
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.