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Systemic lupus erythematosus (SLE) is usually regarded as a relative contraindication for deceased kidney donation. The pathological variations because of the changes in the immune environment after kidney transplantation (KT) are unclear, and the recovery of renal function is poorly understood. We present a case of KT from a deceased donor with SLE who was followed-up for one year. Although SLE-related hemangioma developed during the perioperative period, it was cured after interventional treatment. A pre-planned biopsy was performed one year after KT, and it was found that most of the pathological changes and immunofluorescent markers of lupus had resolved. Renal function was stable, and urinary protein and occult blood levels reduced one year after KT.
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Trasplante de Riñón , Lupus Eritematoso Sistémico , Donantes de Tejidos , Humanos , Lupus Eritematoso Sistémico/diagnóstico , Femenino , Estudios de Seguimiento , Hemangioma , Adulto , Riñón/patología , Persona de Mediana EdadRESUMEN
Lung adenocarcinoma (LUAD) is the leading cause of cancer-related death worldwide. Cancer-associated fibroblasts (CAFs) are a special type of fibroblasts, which play an important role in the development and immune escape of tumors. Weighted gene co-expression network analysis (WGCNA) was used to construct the co-expression module. In combination with univariate Cox regression and analysis of least absolute shrinkage operator (LASSO), characteristics associated with CAFs were developed for a prognostic model. The migration and proliferation of lung cancer cells were evaluated in vitro. Finally, the expression levels of proteins were analyzed by Western blot. LASSO Cox regression algorithm was then performed to select hub genes. Finally, a total of 2 Genes (COL5A2, COL6A2) were obtained. We then divided LUAD patients into high- and low-risk groups based on CAFs risk scores. Survival analysis, CAFs score correlation analysis and tumor mutation load analysis showed that COL5A2 and COL6A2 were high-risk genes for LUAD. Human Protein Atlas (HPA), western blot and PCR results showed that COL5A2 and COL6A2 were up-regulated in LUAD tissues. When COL5A2 and COL6A2 were knocked down, the proliferation, invasion and migration of lung cancer cells were significantly decreased. Finally, COL5A2 can affect LUAD progression through the Wnt/ß-Catenin and TGF-ß signaling pathways. Our CAFs risk score model offers a new approach for predicting the prognosis of LUAD patients. Furthermore, the identification of high-risk genes COL5A2 and COL6A2 and drug sensitivity analysis can provide valuable candidate clues for clinical treatment of LUAD.
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Adenocarcinoma del Pulmón , Fibroblastos Asociados al Cáncer , Neoplasias Pulmonares , Humanos , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/mortalidad , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/mortalidad , Fibroblastos Asociados al Cáncer/metabolismo , Fibroblastos Asociados al Cáncer/patología , Pronóstico , Regulación Neoplásica de la Expresión Génica , Inmunoterapia/métodos , Proliferación Celular/genética , Biomarcadores de Tumor/genética , Colágeno Tipo V/genética , Movimiento Celular/genética , Línea Celular Tumoral , Masculino , Femenino , Análisis de SupervivenciaRESUMEN
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.
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Alginatos , Antineoplásicos , Quitina , Doxorrubicina , Hidrogeles , Nanofibras , Quitina/química , Quitina/análogos & derivados , Alginatos/química , Nanofibras/química , Animales , Doxorrubicina/química , Doxorrubicina/farmacología , Hidrogeles/química , Antineoplásicos/farmacología , Antineoplásicos/química , Humanos , Ratones , Sistemas de Liberación de Medicamentos , Portadores de Fármacos/química , Liberación de Fármacos , Materiales Biocompatibles/química , Inyecciones , Línea Celular TumoralRESUMEN
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.
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Carcinoma Hepatocelular , Quitosano , Indoles , Neoplasias Hepáticas , Polímeros , Humanos , Carcinoma Hepatocelular/cirugía , Neoplasias Hepáticas/cirugía , Quitosano/farmacología , Recurrencia Local de Neoplasia/prevención & control , Hemostasis , Microambiente TumoralRESUMEN
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.
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Trasplante de Hígado , Daño por Reperfusión , Serpinas , Humanos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Hígado/metabolismo , Perfusión , Daño por Reperfusión/prevención & control , Daño por Reperfusión/metabolismo , Serpinas/metabolismoRESUMEN
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.
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Deficiencia de Colina , Hígado Graso , Humanos , Ratones , Animales , Metionina , Hígado Graso/etiología , Racemetionina , Dieta , Ácidos y Sales Biliares , Aldehído Deshidrogenasa Mitocondrial/genética , Ratones Endogámicos C57BLRESUMEN
INTRODUCTION: In order to maximize the utilization of precious donor liver, precisely determining potential hepatocellular carcinoma (HCC) candidates who will benefit from liver transplantation (LT) is essential. As a crucial diagnostic biomarker for HCC, protein induced by vitamin K absence or antagonist-II (PIVKA-II) has become one of the key indicators for assessing tumor recurrence risk after LT. This study aims to investigate the role of PIVKA-II in recipient selection and prognostic stratification. METHODS: The clinicopathologic data of HCC patients undergoing LT from 2015 to 2020 in six Chinese transplant centers were collected. Univariate and multivariate analyses were performed to determine risk factors for disease free survival (DFS). Based on these risk factors, survival analysis was made by Kaplan-Meier method and their value in prognostic stratification was assessed. RESULTS: A total of 522 eligible HCC patients with pre-LT PIVKA-II records were finally included in this study. Tumor burden>8 cm, α-fetoprotein>400 ng/ml, histopathologic grade III and PIVKA-II>240 mAU/ml were identified as independent risk factors for DFS. DFS of patients with PIVKA-II≤240 mAU/ml ( N =288) were significantly higher than those with PIVKA-II>240 mAU/ml ( N =234) (1-year, 3-year, and 5-year DFS: 83.2, 77.3, and 75.9% vs. 75.1, 58.5, and 50.5%; P <0.001). Compared with Hangzhou criteria ( N =305), incorporating PIVKA-II into Hangzhou criteria (including tumor burden, α-fetoprotein, and histopathologic grade) increased the number of patients with eligibility for LT by 21.6% but achieved comparable DFS and overall survival. CONCLUSIONS: Incorporating PIVKA-II into existing LT criteria could increase the number of eligible HCC patients without compromising post-LT outcomes.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Trasplante de Hígado , Humanos , alfa-Fetoproteínas/metabolismo , Biomarcadores , Estudios Retrospectivos , Recurrencia Local de Neoplasia , Donadores Vivos , Vitamina K , Biomarcadores de TumorRESUMEN
[This retracts the article DOI: 10.3892/etm.2014.1570.].
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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.
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Trasplante de Hígado , Humanos , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos , Factores de Tiempo , Donadores Vivos , Drenaje/efectos adversos , Drenaje/métodos , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/terapia , Tiempo de Internación , Albúmina Sérica , HospitalesRESUMEN
Liver and kidney failure can lead to extensive accumulation of toxic metabolites in the blood and tissues, such as bilirubin, blood ammonia, endotoxins, cytokines, creatinine, uric acid, and urea, which aggravate the progression of the disease. Hemoperfusion can effectively adsorb and remove toxins from the blood and treat liver and kidney failure. However, the adsorption efficiency and safety of traditional hemoperfusion adsorbents are not ideal. Thus, it is urgent to develop adsorbents with good blood compatibility, as well as high adsorption and strong selective capacities, to fulfill the clinical needs. In recent years, new hemoperfusion adsorbents with improved adsorption performance and good blood compatibility have been developed. This review classifies and summarizes the recent research progress in hemoperfusion adsorbents for common blood toxins (bilirubin, blood ammonia, endotoxins, cytokines, creatinine, uric acid, and urea) produced by liver and kidney failure. The composition and structure of various toxin adsorbents, toxin adsorption performance, biocompatibility, blood safety, and the adsorption mechanisms of toxins are discussed. Based on a summary of recent studies, feasible strategies have been explored for designing and preparing hemoperfusion adsorbents to fulfill future development requirements. The trends and clinical application prospects of various toxin adsorbents are also discussed.
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Ischemia-reperfusion injury is an important cause of liver injury occurring during liver transplantation. It is usually caused by inflammatory response and oxidative stress-induced oxidative damage. Pachymic acid (PA) has various biological activities such as anti-inflammatory, antioxidant and anti-cancer. However, the action mechanism of PA in hepatic ischemia-reperfusion injury is currently unknown. In this study, liver cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to simulate a hepatic ischemia-reperfusion injury model. The binding relationship between PA and sirtuin 1 (SIRT1) was analyzed by molecular docking. Cell viability was detected by Cell Counting Kit-8. Expression levels of SIRT1 and high mobility group box 1 (HMGB1) were detected by western blot. Subsequent levels of inflammatory factors were detected by related kits and western blot. Meanwhile, related kits were used to examine levels of oxidative stress markers including reactive oxygen species, malondialdehyde, superoxide dismutase and cytotoxicity-associated lactate dehydrogenase. Finally, cell apoptosis was detected by flow cytometry and western blot. The results showed that PA significantly ameliorated OGD/R-induced decrease in SIRT1 expression, increase in HMGB1 acetylation and HMGB1 translocation. Moreover, the elevated levels of inflammatory factors, oxidative stress indexes and cell apoptosis upon exposure to OGD/R were reversed by PA treatment. Moreover, the addition of SIRT1 agonist and inhibitor further demonstrated that PA exerted the aforementioned effects in OGD/R-exposed cells by targeting SIRT1. Thus, the present study revealed the mechanism by which PA ameliorated OGD/R-induced hepatic injury via SIRT1. These results might provide a clearer theoretical basis for the targeted treatment of OGD/R-induced hepatic injury with PA.
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Proteína HMGB1 , Daño por Reperfusión , Ratas , Animales , Humanos , Oxígeno/metabolismo , Oxígeno/farmacología , Glucosa/metabolismo , Sirtuina 1/metabolismo , Sirtuina 1/farmacología , Ratas Sprague-Dawley , Acetilación , Proteína HMGB1/metabolismo , Proteína HMGB1/farmacología , Simulación del Acoplamiento Molecular , Daño por Reperfusión/prevención & control , Daño por Reperfusión/metabolismo , Estrés Oxidativo , Hepatocitos/metabolismo , ApoptosisRESUMEN
BACKGROUND: Hepatic ischemia-reperfusion injury (IRI) in donation after cardiac death (DCD) donors is a major determinant of transplantation success. Endoplasmic reticulum (ER) stress plays a key role in hepatic IRI, with potential involvement of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) pathway and the antiapoptotic protein hematopoietic-lineage substrate-1-associated protein X-1 (HAX1). In this study, we aimed to investigate the effects of hypothermic oxygenated perfusion (HOPE), an organ preservation modality, on ER stress and apoptosis during hepatic IRI in a DCD rat model. METHODS: To investigate whether HOPE could improve IRI in DCD livers, levels of different related proteins were examined by western blotting and quantitative real-time polymerase chain reaction. Further expression analyses, immunohistochemical analyses, immunofluorescence staining, terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, and transmission electron microscopy were conducted to analyze the effects of HOPE on ER stress and apoptosis. To clarify the role of the JAK2/STAT3 pathway and HAX1 in this process, AG490 inhibitor, JAX1 plasmid transfection, co-immunoprecipitation (CO-IP), and flow cytometry analyses were conducted. RESULTS: HOPE reduced liver injury and inflammation while alleviating ER stress and apoptosis in the DCD rat model. Mechanistically, HOPE inhibited unfolded protein responses by activating the JAK2/STAT3 pathway, thus reducing ER stress and apoptosis. Moreover, the activated JAK2/STAT3 pathway upregulated HAX1, promoting the interaction between HAX1 and SERCA2b to maintain ER calcium homeostasis. Upregulated HAX1 also modulated ER stress and apoptosis by inhibiting the inositol-requiring enzyme 1 (IRE1) pathway. CONCLUSIONS: JAK2/STAT3-mediated upregulation of HAX1 during HOPE alleviates hepatic ER stress and apoptosis, indicating the JAK2/STAT3/HAX1 pathway as a potential target for IRI management during DCD liver transplantation.
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Janus Quinasa 2 , Factor de Transcripción STAT3 , Animales , Ratas , Hígado , Estrés del Retículo Endoplásmico , PerfusiónRESUMEN
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.
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Osteoporosis , Ovario , Femenino , Ratones , Animales , Hidrogeles/farmacología , Quitina , Hormonas , EsteroidesRESUMEN
Donor-derived infection (DDI) associated with Scedosporium spp is extremely rare, and results in a very poor prognosis. The present study reports a probable DDI due to Scedosporium boydii (S. boydii) from a donor with neuropsychiatric systemic lupus erythematosus. Two recipients developed Scedosporiosis after kidney transplantation from the same donor. Recipient 1 died of central nervous system infection due to S. boydii based on the clinical presentations, and the positive metagenomic next-generation sequencing (mNGS) and culture results for the cerebrospinal fluid. The other recipient with urinary tract obstruction due to S. boydii, which was identified through the positive culture and mNGS results of the removed stents, was successfully treated by stent replacement and voriconazole administration. Undiagnosed disseminated donor infection and the transmission of S. boydii should be given attention, particularly when the donor and recipients have primary immunodeficiency disease. The screening of donors and recipients for S. boydii using mNGS may be helpful in guiding antifungal prophylaxis and treatment recipients, due to its higher sensitivity and shorter diagnostic time relative to other traditional techniques.
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Infecciones Fúngicas Invasoras , Trasplante de Riñón , Lupus Eritematoso Sistémico , Humanos , Trasplante de Riñón/efectos adversos , Voriconazol/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológicoRESUMEN
Obstructive jaundice is a common clinical symptom generally caused by bile duct stones, inflammatory hyperplasia, and tumors. It is characterized by hyperbilirubinemia and may trigger a variety of complications such as hypotension, kidney injury, endotoxemia, multiple organ dysfunction syndrome, and even death (Pavlidis and Pavlidis, 2018; Liu et al., 2021). Relieving bile duct obstruction and providing adequate drainage have been considered as the most effective therapies for obstructive jaundice. However, it has not yet been established whether it is beneficial to treat affected patients by pre-operative biliary drainage (Blacker et al., 2021). Moreover, the pathophysiological changes or mechanisms associated with the reversal of organ function following the relief of bile-duct obstruction are unclear (Huang et al., 2004). Therefore, it is necessary to establish an experimental model of reversible obstructive jaundice to simulate biliary drainage in clinical practice.
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Ictericia Obstructiva , Animales , Ratas , Ictericia Obstructiva/etiología , Ictericia Obstructiva/cirugía , Modelos Animales de EnfermedadRESUMEN
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.
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Hipoparatiroidismo , Glándulas Paratiroides , Humanos , Trasplante Autólogo , Glándulas Paratiroides/cirugía , Criopreservación , Complicaciones PosoperatoriasRESUMEN
Hepatocellular carcinoma (HCC) is the fourth most common cause of cancer-related deaths in the world. However, there are currently few clinical diagnosis and treatment options available, and there is an urgent need for novel effective approaches. More research is being undertaken on immune-associated cells in the microenvironment because they play a critical role in the initiation and development of HCC. Macrophages are specialized phagocytes and antigen-presenting cells (APCs) that not only directly phagocytose and eliminate tumor cells, but also present tumor-specific antigens to T cells and initiate anticancer adaptive immunity. However, the more abundant M2-phenotype tumor-associated macrophages (TAMs) at tumor sites promote tumor evasion of immune surveillance, accelerate tumor progression, and suppress tumor-specific T-cell immune responses. Despite the great success in modulating macrophages, there are still many challenges and obstacles. Biomaterials not only target macrophages, but also modulate macrophages to enhance tumor treatment. This review systematically summarizes the regulation of tumor-associated macrophages by biomaterials, which has implications for the immunotherapy of HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patología , Neoplasias Hepáticas/patología , Macrófagos Asociados a Tumores , Materiales Biocompatibles , Macrófagos , Microambiente TumoralRESUMEN
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.
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Quitosano , Cicatrización de Heridas , Animales , Ratas , Quitosano/farmacología , Proteómica , Piel , Metaloendopeptidasas/metabolismoRESUMEN
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.