RESUMEN
Achieving hemostasis is a necessary intervention to rapidly and effectively control bleeding. Conventional hemostatic materials currently used in clinical practice may aggravate the damage at the bleeding site due to factors such as poor adhesion and poor adaptation. Compared to most traditional hemostatic materials, polymer-based hemostatic materials have better biocompatibility and offer several advantages. They provide a more effective method of stopping bleeding and avoiding additional damage to the body in case of excessive blood loss. Various hemostatic materials with greater functionality have been developed in recent years for different organs using diverse design strategies. This article reviews the latest advances in the development of polymeric hemostatic materials. We introduce the coagulation cascade reaction after bleeding and then discuss the hemostatic mechanisms and advantages and disadvantages of various polymer materials, including natural, synthetic, and composite polymer hemostatic materials. We further focus on the design strategies, properties, and characterization of hemostatic materials, along with their applications in different organs. Finally, challenges and prospects for the application of hemostatic polymeric materials are summarized and discussed. We believe that this review can provide a reference for related research on hemostatic materials, contributing to the further development of polymer hemostatic materials.
Asunto(s)
Materiales Biocompatibles , Hemostasis , Hemostáticos , Hemostáticos/química , Hemostáticos/farmacología , Hemostáticos/uso terapéutico , Humanos , Hemostasis/efectos de los fármacos , Materiales Biocompatibles/química , Animales , Polímeros/química , Hemorragia/tratamiento farmacológicoRESUMEN
Sorting nexin17 (SNX17) is a member of the sorting nexin family, which plays a crucial role in endosomal trafficking. Previous research has shown that SNX17 is involved in the recycling or degradation of various proteins associated with neurodevelopmental and neurological diseases in cell models. However, the significance of SNX17 in neurological function in the mouse brain has not been thoroughly investigated. In this study, we generated Snx17 knockout mice and observed that the homozygous deletion of Snx17 (Snx17-/-) resulted in lethality. On the other hand, heterozygous mutant mice (Snx17+/-) exhibited anxiety-like behavior with a reduced preference for social novelty. Furthermore, Snx17 haploinsufficiency led to impaired synaptic transmission and reduced maturation of dendritic spines. Through GST pulldown and interactome analysis, we identified the SRC kinase inhibitor, p140Cap, as a potential downstream target of SNX17. We also demonstrated that the interaction between p140Cap and SNX17 is crucial for dendritic spine maturation. Together, this study provides the first in vivo evidence highlighting the important role of SNX17 in maintaining neuronal function, as well as regulating social novelty and anxiety-like behaviors.
Asunto(s)
Espinas Dendríticas , Nexinas de Clasificación , Animales , Ratones , Espinas Dendríticas/metabolismo , Homocigoto , Transporte de Proteínas , Eliminación de Secuencia , Nexinas de Clasificación/genética , Nexinas de Clasificación/metabolismoRESUMEN
Chloroquine, a prototype anti-malaria drug, has been reported to possess anti-inflammatory effects. Moreover, chloroquine pretreatment could improve DNA damage repair. It is therefore reasonable to hypothesize that chloroquine pretreatment could attenuate ischemia/reperfusion injury in the brain. Considering the fact that chloroquine could also improve glucose metabolism, we speculated that the potential effects of chloroquine on ischemia/reperfusion injury might be particularly pronounced in diabetic mice. In this study, chloroquine pretreatment protected neurons from Oxygen Glucose Deprivation (OGD) induced cytotoxicity and apoptosis. In vivo, Ob/ob mice and wildtype (WT) mice were pretreated with chloroquine for 3â¯weeks. Then, ischemic stroke was induced by 60â¯min Middle Cerebral Artery Occlusion (MCAO). We found that chloroquine pretreatment normalized blood glucose in diabetic ob/ob mice, and reduced cerebral damage after ischemic stroke especially for diabetic mice. In addition, chloroquine pretreatment reduced High-mobility group box 1 (HMGB1) content in the cerebrospinal fluid (CSF) and serum and lowered myeloperoxidase (MPO) activity and inflammatory cytokines gene expression both in the ob/ob diabetic mice and WT mice. Moreover, harmful DNA damage-signaling responses, including PARP activation and p53 activation, were also attenuated by chloroquine pretreatment in these two kinds of mice. In conclusion, chloroquine pretreatment could reduce cerebral damage after ischemic stroke especially in diabetic mice through multiple mechanisms, which include reducing neural cell DNA injury, restoring euglycemia and anti-inflammatory effects. The findings may provide potential for the development of chloroquine in the prevention and treatment of stroke in diabetic high-risk patients.
Asunto(s)
Isquemia Encefálica/fisiopatología , Encéfalo/efectos de los fármacos , Cloroquina/administración & dosificación , Diabetes Mellitus/fisiopatología , Fármacos Neuroprotectores/administración & dosificación , Daño por Reperfusión/fisiopatología , Animales , Glucemia/efectos de los fármacos , Encéfalo/patología , Encéfalo/fisiopatología , Isquemia Encefálica/prevención & control , Supervivencia Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Proteína HMGB1/líquido cefalorraquídeo , Ratones Endogámicos C57BL , Neuronas/efectos de los fármacos , Neuronas/patología , Neuronas/fisiología , Cultivo Primario de Células , Daño por Reperfusión/prevención & controlRESUMEN
AIMS: To investigate the possibility of identifying a subtype of latent autoimmune diabetes in adults (LADA), T-LADA (T cell responses-positive and autoantibody-negative) from patients with phenotypic type 2 diabetes (T2D) by enzyme-linked immunospot (ELISPOT). METHODS: Eighty-two patients with phenotypic T2D were studied. Autoantibodies against glutamic acid decarboxylase (GAD), insulinoma-associated protein-2 and zinc transporter 8 were measured by radioligand assay. Thirty-nine Ab+ and 43 Ab- patients with phenotypic T2D were enrolled for T cell assay of responses to GAD65 and C-peptide antigen by ELISPOT. RESULTS: (1) Eleven of 43 Ab- participants with phenotypic T2D were demonstrated interferon (IFN)-γ secreting T cells by ELISPOT, while 13 of 39 Ab+ patients with phenotypic T2D were positive for T cells responses to islet antigens. (2) The onset ages of T cell+ people with phenotypic T2D were younger than that of T cell- individuals (42.7 ± 9.3 vs. 48.2 ± 10.2 years, P = 0.025). Moreover, T cell+ patients with T2D displayed a significantly lower fasting C-peptide (FCP) compared with T cell- participants [0.28 (0.02-0.84) vs. 0.42 (0.05-1.26) nmol/L, P = 0.013]. (3) Ab-T+ group had a significantly lower FCP compared with Ab-T- group [0.31 (0.13-0.84) vs. 0.51 (0.07-1.26) nmol/L, P = 0.023]. CONCLUSIONS: By measuring T cell responses to islet antigens in patients with phenotypic T2D, we identified a specific subtype of LADA who may be associated with worse basal ß-cell function than classic T2D (Ab-T-).
Asunto(s)
Diabetes Mellitus Tipo 2/inmunología , Diabetes Autoinmune Latente del Adulto/inmunología , Fenotipo , Linfocitos T/inmunología , Adulto , Autoanticuerpos/inmunología , Péptido C/metabolismo , Diabetes Mellitus Tipo 2/sangre , Femenino , Glutamato Descarboxilasa/inmunología , Humanos , Diabetes Autoinmune Latente del Adulto/sangre , Diabetes Autoinmune Latente del Adulto/clasificación , Masculino , Persona de Mediana Edad , Transportador 8 de Zinc/inmunologíaRESUMEN
Insulin receptor substrate 2 (IRS2) is a component of the insulin/insulin-like growth factor 1 (IGF1) signaling cascade, which plays an important role in mouse hypothalamic and ovarian functions. The present study was conducted to investigate the role of IRS2 in steroidogenesis, apoptosis, cell cycle and proliferation in mouse granulosa cells (GCs). Flow cytometry and CCK8 assay showed that IRS2 knockdown inhibited cell proliferation, reduced cell viability, and increased apoptosis in GCs. The study also revealed that the expression of Cyclin A1, Cyclin B1 and Bcl2 was downregulated, while the expression of Bax, Cyclin D1 and Cyclin D2 was upregulated. ELISA analysis showed that IRS2 knockdown decreased the concentrations of estradiol (E2) and progesterone (P4), which was further validated by the decreased expression of Star, Cyp11a1, and Cyp19a1. Moreover, IRS2 knockdown altered the expression of Has2 and Ptgs2, which are essential for folliculogenesis. In addition, we found that IRS2-mediated cell viability and hormone secretion are dependent on the PI3K/AKT signaling pathway. Collectively, this study demonstrated that IRS2 plays an important role in the regulation of cell proliferation and steroidogenesis in mouse GCs via the PI3K/AKT signaling pathway.
Asunto(s)
Células de la Granulosa/metabolismo , Hormonas/metabolismo , Proteínas Sustrato del Receptor de Insulina/metabolismo , Animales , Apoptosis , Aromatasa/metabolismo , Ciclo Celular , Proliferación Celular , Supervivencia Celular , Enzima de Desdoblamiento de la Cadena Lateral del Colesterol/metabolismo , Medios de Cultivo , Estradiol/metabolismo , Femenino , Citometría de Flujo , Factor I del Crecimiento Similar a la Insulina/metabolismo , Ratones , Fosfoproteínas/metabolismo , Progesterona/metabolismo , Transducción de SeñalRESUMEN
OBJECTIVE: To explore the type of cytokine (IL-2 or IL-7) and its most optimal concentration regarding the improvement of the signal-to-noise ratio of glutamic acid decarboxylase 65 (GAD65) in enzyme-linked immunospot (ELISPOT) assay in Type 1 diabetic (T1DM) patients.⩠Methods: Twenty T1DM patients (Group A) and sixteen healthy controls matched with age and sex (Group B) were enrolled in our study, and their peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll method. GAD65, internal control and Pediacel served as "five-for-one" vaccine were selected as the stimulating antigen. Different concentrations of IL-2 [0 U/mL (Group 1), 0.5 U/mL (Group 2), 2.5 U/mL (Group 3) and 12.5 U/mL (Group 4)] were added to the culture system. The CD4+ T cells of secreting interferon-gamma (IFN-γ) in the above groups were determined by ELISPOT. The spots number, net values and stimulating index (SI) were compared in GAD65 (signal) and internal control (background). Next, another 21 T1DM patients (Group C)and 12 healthy controls matched with age and sex (Group D) were enrolled, and the specific T cell response to the GAD65 antigen was detected. The net values and SI were compared between the best optimal concentration of IL-2 (2.5 U/mL, Group 5) and IL-7 (0.5 ng/mL, Group 6).⩠Results: 1) After adding IL-2 into the Group A, the amount of GAD65 reactive T cells in different groups increased compared with Group A1, while the background in the internal control also increased gradually with the increased concentration of IL-2. There was no significant difference in net value (signal-noise) in the different concentration between the Group A3 and the Group A4 (P>0.05). The SI in the Group A3 (2.8), the highest one, was significantly higher than that in the Group B3 (1.3) (P<0.05). 2) Although the number of GAD65 spots in the Group C6 and the Group D6 were slightly higher than that in the Group C5 and the Group D5, respectively, the background in the Group C6 and the Group D6 also increased, without statistical significance (P>0.05). The mean net value spot and SI in the Group C5 (net value: 5.5; SI: 2.8) were both significantly higher than those in the Group C6 (net value: 4.3; SI: 1.8) (both P<0.05).⩠Conclusion: The concentration of 2.5 U/mL for IL-2 is proved to be the best optimal concentration for GAD65 specific T-cell responses in ELISPOT in patients with T1DM. IL-2 is much better than IL-7 in improvement of the SI in the ELISPOT.
Asunto(s)
Linfocitos T CD4-Positivos/efectos de los fármacos , Diabetes Mellitus Tipo 1/inmunología , Glutamato Descarboxilasa/inmunología , Interleucina-2/farmacología , Interleucina-7/farmacología , Leucocitos Mononucleares/efectos de los fármacos , Linfocitos T CD4-Positivos/inmunología , Estudios de Casos y Controles , Diabetes Mellitus Tipo 1/sangre , Ensayo de Immunospot Ligado a Enzimas , Glutamato Descarboxilasa/sangre , Humanos , Inmunidad Celular , Interferón gamma/efectos de los fármacos , Interferón gamma/inmunología , Interleucina-2/administración & dosificación , Interleucina-7/administración & dosificación , Leucocitos Mononucleares/inmunología , Relación Señal-RuidoRESUMEN
OBJECTIVE: To explore the better freezing protocol to preserve peripheral blood monuclear cells (PBMCs), islets antigen-specific T cells responses compared with freshly isolated samples in type 1 diabetic (T1D) patients. METHODS: The T cell Workshop Committee of the Immunology of Diabetes Society (IDS-TCW) organized the Freezing Study I and we were one of the 9 centers in the world to participate in the study. According to the two standardized T cell freezing protocols (warm and cold) to freshly isolated PBMCs in terms of recovery, viability, cell subset composition (FACS) and performance in Enzyme-linked immunospot (ELISPOT) assays, we chose 5 newly onset T1D patients and 5 age and sex matched healthy controls. Besides the protocols, all the freezing reagents and antigens were also centralized. The antigens used in ELISPOT were labeled blindedly. RESULTS: 1) Although warm frozen-thawed (W) samples had a slightly higher recovery rate (61.2% vs 60.1%, P>0.05) and viability (77.5% vs 74.9%, P>0.05) as compared with the cold frozen ones (C), the difference was not significant. 2) Both protocols led to a relative loss in monocytes as compared with the fresh samples (F) [3.2±1.1% (C) and 3.0±0.9% (W) vs 7.0±1.1% (F), both P<0.05], while other subsets including CD4+T, CD8+T, B cells, NK cells and NKT cells didn't. 3) Freezing and fresh samples showed similar IFN-γ secretion responses to polystimuli in ELISPOT. Irrespective of the freezing protocol, recall antigen Pediacel and islet antigen-reactive responses were both lower in the frozen cells compared with fresh PBMCs. The stimuli index (SI) of GADspecific T cell response in the fresh samples from T1D patients was 5.1, higher than that of frozen samples with either cold protocol (1.3) or warm one (1.4) (both P<0.05). Only fresh samples from T1D showed significantly higher GAD-specific T cell responses than the healthy controls no matter in SI (5.1 vs 0.9, P<0.05) or spot forming cells (8.1 vs 0.1, P<0.05), whereas the frozen samples did not show such difference. CONCLUSION: More studies are needed to verify a freezing method to bring comparable islets antigen specific T cell responses in T1D patients to fresh PBMCs.