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1.
Liver Transpl ; 29(7): 711-723, 2023 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-36749821

RESUMEN

Antibody-mediated rejection (AMR) is a refractory rejection after ABO blood-type incompatible (ABOi) or donor-specific antibody (DSA)-positive liver transplantation (LT). Pretransplant rituximab desensitization dramatically reduced posttransplant AMR development; however, risk factors for AMR in the rituximab era remain unclear in both ABOi living-donor LT (ABOi-LDLT) and preformed DSA-positive LT (pDSA-LT). Of our 596 adult LDLTs (≥18 y) after rituximab introduction (2004-2019), 136 were ABOi-LDLT (22.8%). After excluding retransplants (9), acute liver failure (7), and protocol deviations (16), 104 ABOi-LDLTs were finally enrolled. Of these, 19 recipients developed AMR, 18 of which occurred within 2 weeks after transplantation (95%). ABOi-AMR significantly worsened graft and recipient survival than those without ( p =0.02 and 0.04, respectively). Model for End-stage Liver Disease (MELD) ≤13 (OR: 5.15 [1.63-16.3], p =0.005) and pre-rituximab anti-ABO IgM-titer ≥128 (OR: 3.25 [1.05-10.0], p =0.03) were identified as independent risk factors for ABOi-AMR development. Recipients fulfilling both factors showed significantly worse survival rates than those who did not ( p =0.003). Of 352 adult LTs, after introducing the LABScreen Single Ag method (2009-2019), pDSA with mean fluorescence intensity (MFI) ≥500 was detected in 50 cases (14.2%). After excluding 10 ABOi-LDLTs, 40 pDSA-LTs were finally analyzed, of which 5 developed AMR. The combination of high-titer (sum-MFI ≥10,000) and multi-loci pDSAs was a significant risk factor for pDSA-AMR development ( p <0.001); however, it did not affect the 5-year recipient survival compared with those without ( p =0.56). In conclusion, preoperative MELD ≤13 and pre-rituximab anti-ABO IgM-titer ≥128 for ABOi-LDLT, and the combination of sum-MFI ≥10,000 and multi-loci pDSAs for pDSA-LT, are risk factors for AMR in the era of rituximab desensitization. Characteristically, ABOi-AMR significantly deteriorated graft and recipient survival, whereas pDSA-AMR did not.


Asunto(s)
Enfermedad Hepática en Estado Terminal , Trasplante de Hígado , Adulto , Humanos , Rituximab/uso terapéutico , Trasplante de Hígado/efectos adversos , Trasplante de Hígado/métodos , Enfermedad Hepática en Estado Terminal/etiología , Incompatibilidad de Grupos Sanguíneos , Índice de Severidad de la Enfermedad , Donadores Vivos , Factores de Riesgo , Inmunoglobulina M , Sistema del Grupo Sanguíneo ABO , Rechazo de Injerto/epidemiología , Rechazo de Injerto/prevención & control , Supervivencia de Injerto
2.
FASEB J ; 36(11): e22585, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36190433

RESUMEN

RNA polymerase II (RNAPII) is an essential machinery for catalyzing mRNA synthesis and controlling cell fate in eukaryotes. Although the structure and function of RNAPII have been relatively defined, the molecular mechanism of its assembly process is not clear. The identification and functional analysis of assembly factors will provide new understanding to transcription regulation. In this study, we identify that RTR1, a known transcription regulator, is a new multicopy genetic suppressor of mutants of assembly factors Gpn3, Gpn2, and Rba50. We demonstrate that Rtr1 is directly required to assemble the two largest subunits of RNAPII by coordinating with Gpn3 and Npa3. Deletion of RTR1 leads to cytoplasmic clumping of RNAPII subunit and multiple copies of RTR1 can inhibit the formation of cytoplasmic clump of RNAPII subunit in gpn3-9 mutant, indicating a new layer function of Rtr1 in checking proper assembly of RNAPII. In addition, we find that disrupted activity of Rtr1 phosphatase does not trigger the formation of cytoplasmic clump of RNAPII subunit in a catalytically inactive mutant of RTR1. Based on these results, we conclude that Rtr1 cooperates with Gpn3 and Npa3 to assemble RNAPII core.


Asunto(s)
ARN Polimerasa II , Proteínas de Saccharomyces cerevisiae , Factores de Transcripción , Monoéster Fosfórico Hidrolasas/genética , ARN Polimerasa II/genética , ARN Mensajero , Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/genética , Factores de Transcripción/genética , Transcripción Genética
3.
Biomacromolecules ; 24(6): 2541-2548, 2023 06 12.
Artículo en Inglés | MEDLINE | ID: mdl-37264927

RESUMEN

The lignin-carbohydrate complexes (LCCs) typically present in the liquors produced in the pre-hydrolysis of biomass cause severe difficulties in downstream fractionation. To address this issue, a series of LCC samples were accessed from solutions obtained from the pre-hydrolysis of extractive-free pine wood meal (H-LCC) and compared with LCC obtained from the corresponding residues (B-LCC). Chromatographic and spectroscopic techniques revealed that 8.2% of the lignins were degraded at 160 °C, resulting from the breakage of ß-O-4' linkages during pre-hydrolysis. Meanwhile, (reactive) hemicelluloses were mainly removed from the fibers' cell walls. Some hemicelluloses in the pre-hydrolysis liquor, such as glucomannans, were associated with degraded lignin fragments via ether and ester bonds. However, the newly formed LCCs were pH-labile and underwent rapid hydrolysis. Overall, we reveal details about LCC formation and degradation during pre-hydrolysis at given temperatures, critically important in efforts to improve biomass processing and valorization.


Asunto(s)
Carbohidratos , Lignina , Lignina/química , Hidrólisis , Espectroscopía de Resonancia Magnética , Carbohidratos/química , Madera/química
4.
World J Surg Oncol ; 21(1): 225, 2023 Jul 26.
Artículo en Inglés | MEDLINE | ID: mdl-37496069

RESUMEN

OBJECTIVE: The purpose of this study was to investigate the relationship between the expression of matrix metalloproteinase-9 (MMP-9) and pathological indexes in papillary thyroid carcinoma (PTC). EVIDENCE OBTAINED: The database was searched in PubMed, Embase, CNKI, and Web of Science databases for relevant clinical trials. The odds ratio (OR) and 95% confidence interval (CI) show the effect of MMP-9 expression and age, tumour size, gender, lymph node metastasis (LNM), and TNM (tumour, lymph node, metastasis) stage. Statistical analysis of the data was performed using Stata 17.0. EVIDENCE SYNTHESIS: A total of 1433 patients with PTC were included in this meta-analysis. MMP-9 expression was significantly correlated with LNM (OR = 3.92, 95% CI = 2.71-5.65, P = 0.000), tumour size (OR = 1.69, 95% CI = 1.13-2.52, P = 0.011), and TNM stage (OR = 2.95, 95% CI = 2.10-4.13, P = 0.000), but not with gender (OR = 0.90, 95% CI = 0.66-1.22, P = 0.487) and age (OR = 1.36, 95% CI = 0.93-1.98, P = 0.115). CONCLUSIONS: Our meta-analysis showed that MMP-9 was significantly associated with LNM, tumour size, and TNM stage; therefore, MMP-9 may be a reliable prognostic biomarker for patients with PTC. However, more high-quality studies are needed to support these findings further.


Asunto(s)
Neoplasias de la Tiroides , Humanos , Relevancia Clínica , Metástasis Linfática , Metaloproteinasa 9 de la Matriz , Cáncer Papilar Tiroideo/patología , Neoplasias de la Tiroides/patología
5.
Liver Transpl ; 28(10): 1588-1602, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35603526

RESUMEN

Donor-recipient human leukocyte antigen (HLA) compatibility has not been considered to significantly affect liver transplantation (LT) outcomes; however, its significance in living-donor LT (LDLT), which is mostly performed between blood relatives, remains unclear. This retrospective cohort study included 1954 LDLTs at our institution (1990-2020). The primary and secondary endpoints were recipient survival and the incidence of T cell-mediated rejection (TCMR) after LDLT, respectively, according to the number of HLA mismatches at all five loci: HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ. Subgroup analyses were also performed in between-siblings that characteristically have widely distributed 0-10 HLA mismatches. A total of 1304 cases of primary LDLTs were finally enrolled, including 631 adults (recipient age at LT ≥18 years) and 673 children (<18 years). In adult-to-adult LDLT, the more HLA mismatches at each locus, the significantly worse the recipient survival was (p = 0.03, 0.01, 0.03, 0.001, and <0.001 for HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ, respectively). This trend was more pronounced when multiple loci were combined (all p < 0.001 for A + B + DR, A + B + C, DR + DQ, and A + B + C + DR + DQ). Notably, a total of three or more HLA-B + DR mismatches was an independent risk factor for both TCMR (hazard ratio [HR] 2.66, 95% confidence interval [CI] 1.21-5.87; p = 0.02) and recipient survival (HR 2.44, 95% CI 1.11-5.35; p = 0.03) in between-siblings. By contrast, HLA mismatch did not affect pediatric LDLT outcomes at any locus or in any combinations; however, it should be noted that all donor-recipient relationships are parent-to-child that characteristically possesses one or less HLA mismatch at each locus and maximally five or less mismatches in total. In conclusion, HLA mismatch significantly affects not only TCMR development but also recipient survival in adult LDLT, but not in children.


Asunto(s)
Trasplante de Hígado , Donadores Vivos , Adulto , Niño , Rechazo de Injerto/epidemiología , Supervivencia de Injerto , Antígenos HLA , Antígenos HLA-A , Antígenos HLA-B , Antígenos HLA-C , Antígenos HLA-DQ , Antígenos HLA-DR , Prueba de Histocompatibilidad , Humanos , Trasplante de Hígado/efectos adversos , Estudios Retrospectivos
6.
BMC Cardiovasc Disord ; 22(1): 487, 2022 Nov 16.
Artículo en Inglés | MEDLINE | ID: mdl-36380270

RESUMEN

OBJECTIVE: We aimed to assess the impact of using enhanced stent visualization (ESV) systems on contrast media volume and radiation dose in percutaneous coronary intervention (PCI), especially for patients with chronic kidney disease (CKD). BACKGROUND: Coronary heart disease (CHD) is associated with chronic kidney disease (CKD), as they share a similar pathological pathway. In addition, the iodinated contrast media used for angiography is a risk factor for contrast-associated acute kidney injury (CA-AKI), which could aggravate the progression of CKD. We hypothesized that ESV systems have the potential to reduce the use of contrast media as well as the radiation dose; however, few studies have reported the impact on contrast media with the use of ESV systems. METHODS: We retrospectively collected 124 patients with acute coronary syndrome who underwent PCI from May 2020 to July 2021. The patients were divided into the ESV-guided group (n = 64) and angiography-guided group (n = 60). Procedural parameters, including contrast media volume, radiation exposure (in Air Kerma-AK and Dose Area Product-DAP), number of cines, cine frames, fluoroscopy and procedure time, were recorded and analysed. RESULTS: The groups were comparable regarding the patient characteristics. There was a significant reduction in contrast media volume (174.7 ± 29.6 ml vs.132.6 ± 22.3 ml, p = 0.0001), radiation exposure (776 (499 - 1200) mGy vs. 1065 (791 - 1603) mGy, p = 0.002 in AK; 43 (37 - 73) Gycm2 vs. 80 (64 - 133) Gycm2, p = 0.030 in DAP) and procedure time (53.06 ± 21.20 min vs. 72.00 ± 30.55 min, p = 0.01) with the use of ESV systems. Similar results were observed in the subgroup analysis for the patients with CKD. CONCLUSION: This study suggested that the use of ESV is associated with reduced contrast media usage, radiation dose and procedure time during PCI. The same results were observed in a subgroup analysis in patients with CKD, and this shows that ESV-guided PCI has the potential to reduce renal impairment and mitigate the progression of CKD for those CHD patients with CKD.


Asunto(s)
Intervención Coronaria Percutánea , Exposición a la Radiación , Insuficiencia Renal Crónica , Humanos , Intervención Coronaria Percutánea/efectos adversos , Intervención Coronaria Percutánea/métodos , Medios de Contraste/efectos adversos , Angiografía Coronaria/efectos adversos , Angiografía Coronaria/métodos , Estudios Retrospectivos , Dosis de Radiación , Exposición a la Radiación/efectos adversos , Exposición a la Radiación/prevención & control , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Factores de Riesgo , Stents
7.
Proc Biol Sci ; 287(1935): 20201661, 2020 09 30.
Artículo en Inglés | MEDLINE | ID: mdl-32933445

RESUMEN

The bivalved crustacean ostracods have the richest fossil record of any arthropod group and display complex reproductive strategies contributing to their evolutionary success. Sexual reproduction involving giant sperm, shared by three superfamilies of living ostracod crustaceans, is among the most fascinating behaviours. However, the origin and evolution of this reproductive mechanism has remained largely unexplored because fossil preservation of such features is extremely rare. Here, we report exceptionally preserved ostracods with soft parts (appendages and reproductive organs) in a single piece of mid-Cretaceous Kachin amber (approximately 100 Myr old). The ostracod assemblage is composed of 39 individuals. Thirty-one individuals belong to a new species and genus, Myanmarcypris hui gen. et sp. nov., exhibiting an ontogenetic sequence from juveniles to adults (male and female). Seven individuals are assigned to Thalassocypria sp. (Cypridoidea, Candonidae, Paracypridinae) and one to Sanyuania sp. (Cytheroidea, Loxoconchidae). Our micro-CT reconstruction provides direct evidence of the male clasper, sperm pumps (Zenker organs), hemipenes, eggs and female seminal receptacles with giant sperm. Our results reveal that the reproduction behavioural repertoire, which is associated with considerable morphological adaptations, has remained unchanged over at least 100 million years-a paramount example of evolutionary stasis. These results also double the age of the oldest unequivocal fossil animal sperm. This discovery highlights the capacity of amber to document invertebrate soft parts that are rarely recorded by other depositional environments.


Asunto(s)
Crustáceos/anatomía & histología , Genitales Masculinos , Espermatozoides , Ámbar , Animales , Artrópodos , Femenino , Fósiles , Genitales , Masculino , Reproducción , Microtomografía por Rayos X
8.
Inorg Chem ; 59(18): 13502-13516, 2020 Sep 21.
Artículo en Inglés | MEDLINE | ID: mdl-32869994

RESUMEN

Deep-blue-light-emitting materials are urgently desired in high-performance organic light-emitting diodes (OLEDs) for full-color display and solid-state lighting applications. However, the development of stable and efficient deep-blue emitters remains a great challenge. Herein, a series of stable and efficient tetradentate Pd(II)-complex-based deep-blue emitters with rigid 5/6/6 metallocycles and no F atom were designed and synthesized. These deep-blue emitters employ various isoelectronic five-membered heteroaryl-ring-containing ligands to exhibit extremely narrow emission spectra peaking at 439-443 nm with a full width at half-maximum (fwhm) of only 22-38 nm in 2-methyltetrahydrofuran at room temperature. In particular, the design of an intramolecular hydrogen bond enabled the 1-phenyl-1,2,3-trazole-based Pd(II) complexes to achieve CIEy < 0.1 (0.069-0.078; CIE is Commission Internationale de L'Eclairage). Theoretical calculation and natural transition orbital analysis reveal that these deep-blue materials emit light exclusively from their ligand (carbazole)-centered (3LC) states. Moreover, the triplet excited-state property can be efficiently regulated through ligand modification with isoelectronic oxazole and thiazole rings or pyridine rings, resulting in sky-blue-to-yellow materials, which emit light originating from an admixture of metal-to-ligand charge-transfer (3MLCT) and intraligand charge-transfer states. The newly developed Pd(II) complexes are strongly emissive in various matrixes with a quantum efficiency of up to 51% and also highly thermally stable with a 5% weight-reduction temperature (ΔT5%) of up to 400 °C. Deep-blue OLEDs with CIEy < 0.1 employing Pd(II) complexes as emitters were successfully fabricated for the first time. This study demonstrates that the Pd(II) complexes can act as excellent phosphorescent light-emitting materials through rational molecular design and also provide a valuable method for the development of Pd(II)-complex-based efficient and stable deep-blue emitters.

9.
J Cell Mol Med ; 23(2): 1174-1182, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30450674

RESUMEN

The incidence rate of head and neck squamous cell carcinoma (HNSCC) has steadily increased over the past decade. However, treatment options for metastatic HNSCC are often limited and the 5-year survival rate has remained static. Therefore, the development and assessment of more efficient but less toxic therapeutic strategies is an unmet need for treatment of more extensive HNSCC. Here, we report that CYT997, a novel microtubule-disrupting agent, exerts strong activity in inhibiting HNSCC cell invasion and metastasis. The loss of invasion capacity by CYT997 was accompanied by an associated increase in cell adhesion and the reversal of epithelial-mesenchymal transition (EMT). Increased expression of E-cadherin protein and decreased expression of Vimentin protein became evident in HNSCC cells following CYT997 exposure, which were consistently observed in HNSCC xenografts from the mice receiving CYT997. Moreover, the capacity of invasive HNSCC cells to form pulmonary metastases was significantly blocked with CYT997 treatment, indicating that the diminishment of EMT traits contributes to CYT997-suppressed metastasis. Intriguingly, CYT997 impaired intracellular ATP levels in HNSCC cells, at least in part, through its inhibitory effect on the mitochondrial protein IF1. The addition of ATP attenuated CYT997-induced suppression of cell invasion, coupled with down-regulation of E-Cadherin and up-regulation of Vimentin. These findings support a critical role of ATP levels in cell invasion and metastasis under the influence of CYT997. Collectively, our data unveil the mechanism involved in mediating CYT997 action, and provide preclinical rationale for possible clinical application of CYT997 as a novel therapeutic strategy against aggressive HNSCC.


Asunto(s)
Adenosina Trifosfato/metabolismo , Movimiento Celular/efectos de los fármacos , Neoplasias de Cabeza y Cuello/metabolismo , Metástasis de la Neoplasia/tratamiento farmacológico , Piridinas/farmacología , Pirimidinas/farmacología , Carcinoma de Células Escamosas de Cabeza y Cuello/metabolismo , Animales , Cadherinas/metabolismo , Línea Celular Tumoral , Citoplasma/efectos de los fármacos , Citoplasma/metabolismo , Regulación hacia Abajo/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias de Cabeza y Cuello/patología , Humanos , Ratones , Ratones Endogámicos NOD , Invasividad Neoplásica/patología , Metástasis de la Neoplasia/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Factores de Transcripción/metabolismo , Regulación hacia Arriba/efectos de los fármacos , Vimentina/metabolismo
10.
J Recept Signal Transduct Res ; 39(5-6): 470-478, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31829064

RESUMEN

Context: The pathogenesis of cardiomyocyte death is closely associated with mitochondrial homeostasis via poorly understood mechanisms.Objective: The aim of our study is to explore the contribution of large tumor suppressor kinase 2 (LATS2) to the apoptosis of cardiomyocyte H9C2 cells.Materials and Methods: Adenovirus-mediated LATS2 overexpression was carried out in H9C2 cells. The cell viability and apoptosis rate were measured via an MTT assay, TUNEL staining, western blotting, an ELISA, and an LDH release assay. Mitophagy was quantified using immunofluorescence and western blotting.Results: The overexpression of LATS2 in H9C2 cells drastically promoted cell death. Molecular investigations showed that LATS2 overexpression was associated with mitochondrial injury, as evidenced by increased mitochondrial ROS production, reduced antioxidant factor levels, increased cyt-c liberation into the nucleus and activated mitochondrial caspase-9-dependent apoptotic pathway activity. Furthermore, our results demonstrated that LATS2-mediated mitochondrial malfunction by repressing mitophagy and that the reactivation of mitophagy could sustain mitochondrial integrity and homeostasis in response to LATS2 overexpression. Furthermore, we found that LATS2 inhibited mitophagy by inactivating the Prx3-Mfn2 axis. The reactivation of Prx3-Mfn2 pathways abrogated the LATS2-mediated inhibition of mitochondrial apoptosis in H9C2 cells.Conclusions: The overexpression of LATS2 induces mitochondrial stress by repressing protective mitophagy in a manner dependent on Prx3-Mfn2 pathways, thus reducing the survival of H9C2 cells.


Asunto(s)
GTP Fosfohidrolasas/genética , Proteínas de Homeodominio/genética , Proteínas Mitocondriales/genética , Miocitos Cardíacos/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Animales , Apoptosis/genética , Caspasa 9/genética , Supervivencia Celular/genética , Regulación de la Expresión Génica/genética , Homeostasis/genética , Humanos , Mitocondrias/genética , Mitofagia/genética , Ratas , Transducción de Señal/genética
11.
Mol Carcinog ; 57(11): 1616-1625, 2018 11.
Artículo en Inglés | MEDLINE | ID: mdl-30074276

RESUMEN

Although genetic amplification and overexpression of the fibroblast growth factor 19 (FGF19) gene are found in human breast cancer, mechanisms that contribute to such functional alterations remain elusive. We report here that high expression of FGF19 is associated with the aggressive malignant behavior and poor survival outcome of breast cancer patients. FGF19 is particularly highly expressed in luminal molecular subtype of breast tumors and its expression levels are positively associated with its secretion levels from breast cancer cells. Genetic knockout of FGF19 significantly induces repression of breast tumor progression and metastasis in either an orthotopic mouse model of breast cancer or an experimental metastasis model. The FGF19 specific receptor, FGFR4, can be activated and subsequently upregulate AKT signaling in breast cancer cell upon FGF19, which is critical for oncogenic role of FGF19. Inactivation of FGFR4 by its inhibitor BLU9931 significantly attenuates FGF19-induced tumor-promoting activity, suggesting interruption of FGFR4 function is sufficient to affect FGF19-driven breast cancer. Overall, these insights support the idea that targeting FGFR4 in breast cancer cells overexpressing FGF19 may represent an effective strategy to suppress cancer development, progression, and metastasis.


Asunto(s)
Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Factores de Crecimiento de Fibroblastos/metabolismo , Receptor Tipo 4 de Factor de Crecimiento de Fibroblastos/metabolismo , Transducción de Señal , Adulto , Anciano , Animales , Biomarcadores , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Línea Celular Tumoral , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Factores de Crecimiento de Fibroblastos/genética , Eliminación de Gen , Marcación de Gen , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/secundario , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ensayos Antitumor por Modelo de Xenoinjerto
12.
Exp Cell Res ; 361(1): 19-29, 2017 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-28964780

RESUMEN

Gastric cancer tissue-derived mesenchymal stem cells (GC-MSCs) are important resident stromal cells in the tumor microenvironment (TME) and have been shown to play a key role in gastric cancer progression. Whether GC-MSCs exert a tumor-promoting function by affecting anti-tumor immunity is still unclear. In this study, we used GC-MSC conditioned medium (GC-MSC-CM) to pretreat peripheral blood mononuclear cells (PBMCs) from healthy donors. We found that GC-MSC-CM pretreatment markedly reversed the inhibitory effect of PBMCs on gastric cancer growth in vivo, but did not affect functions of PBMCs on gastric cancer cell proliferation, cell cycle and apoptosis in vitro. PBMCs pretreated with GC-MSC-CM significantly promoted gastric cancer migration and epithelial-mesenchymal transition in vitro and liver metastases in vivo. Flow cytometry analysis showed that GC-MSC-CM pretreatment increased the proportion of Treg cells and reduced that of Th17 cells in PBMCs. CFSE labeling and naïve CD4+ T cells differentiation analysis revealed that GC-MSC-CM disrupted the Treg/Th17 balance in PBMCs by suppressing Th17 cell proliferation and inducing differentiation of Treg cells. Overall, our collective results indicate that GC-MSCs impair the anti-tumor immune response of PBMCs through disruption of Treg/Th17 balance, thus providing new evidence that gastric cancer tissue-derived MSCs contribute to the immunosuppressive TME.


Asunto(s)
Leucocitos Mononucleares/inmunología , Células Madre Mesenquimatosas/inmunología , Neoplasias Peritoneales/secundario , Neoplasias Gástricas/patología , Linfocitos T Reguladores/inmunología , Células Th17/inmunología , Animales , Apoptosis , Ciclo Celular , Movimiento Celular , Proliferación Celular , Técnicas de Cocultivo , Medios de Cultivo Condicionados/farmacología , Progresión de la Enfermedad , Transición Epitelial-Mesenquimal , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Neoplasias Peritoneales/inmunología , Neoplasias Peritoneales/patología , Neoplasias Gástricas/inmunología , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
13.
Biochem Biophys Res Commun ; 490(2): 541-551, 2017 08 19.
Artículo en Inglés | MEDLINE | ID: mdl-28629999

RESUMEN

Recently, the intricate relationship between Trimethylamine N-oxide (TMAO) and inflammatory bowel disease (IBD) is of growing interest. The NLRP3 inflammasome plays crucial roles in gut homeostasis and determining the severity of inflammation in IBD, however, the precise roles of the NLRP3 inflammasome in IBD are still debated. ATG16L1 mediates the cellular degradative process of autophagy and is considered a critical regulator of inflammation based on its genetic association with IBD. Whether TMAO prime NLRP3 inflammasome via ATG16L1-induced autophagy remains unclear. This study observed the expression of ATG16L1, LC3-II and p62 and activation of NLRP3 inflammasome stimulated by TMAO in fetal human colon cells (FHCs), aiming to elucidate the mechanism by which the TMAO may contribute to colonic epithelial inflammation. Our results demonstrated that TMAO significantly inhibited ATG16L1, LC3-II and p62 expression, and triggered the activated NLRP3 inflammasome and production of ROS in a dose- and time-dependent manner. Furthermore, TMAO-mediated effects were observably reversed by over-expression ATG16L1 and siRNA-mediated knockdown NLRP3.The present results support the hypothesis that TMAO may be involved in the pathogenesis of IBD by impacting ATG16L1-induced autophagy and activating NLRP3 inflammasome, suggesting a potential therapeutic targets for the treatment of IBD and TMAO-associated complications.


Asunto(s)
Proteínas Relacionadas con la Autofagia/inmunología , Autofagia , Colon/inmunología , Enfermedades Inflamatorias del Intestino/inmunología , Mucosa Intestinal/inmunología , Metilaminas/inmunología , Proteína con Dominio Pirina 3 de la Familia NLR/inmunología , Proteínas Relacionadas con la Autofagia/genética , Línea Celular , Colon/citología , Colon/patología , Regulación hacia Abajo , Humanos , Enfermedades Inflamatorias del Intestino/genética , Enfermedades Inflamatorias del Intestino/patología , Mucosa Intestinal/citología , Mucosa Intestinal/patología , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Interferencia de ARN , ARN Interferente Pequeño/genética , Especies Reactivas de Oxígeno/inmunología
14.
Liver Transpl ; 23(9): 1171-1185, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28650112

RESUMEN

The outcomes of liver transplantation (LT) from donation after cardiac death (DCD) donors remain poor due to severe warm ischemia injury. Perfluorocarbon (PFC) is a novel compound with high oxygen carrying capacity. In the present study, a rat model simulating DCD LT was used, and the impact of improved graft oxygenation provided by PFC addition on liver ischemia/reperfusion injury (IRI) and survival after DCD LT was investigated. Orthotopic liver transplants were performed in male Lewis rats, using DCD liver grafts preserved with cold University of Wisconsin (UW) solution in the control group and preserved with cold oxygenated UW solution with addition of 20% PFC in the PFC group. For experiment I, in a 30-minute donor warm ischemia model, postoperative graft injury was analyzed at 3 and 6 hours after transplantation. For experiment II, in a 50-minute donor warm ischemia model, the postoperative survival was assessed. For experiment I, the levels of serum aspartate aminotransferase, alanine aminotransferase, hyaluronic acid, malondialdehyde, and several inflammatory cytokines were significantly lower in the PFC group. The hepatic expression levels of tumor necrosis factor α and interleukin 6 were significantly lower, and the expression level of heme oxygenase 1 was significantly higher in the PFC group. Histological analysis showed significantly less necrosis and apoptosis in the PFC group. Sinusoidal endothelial cells and microvilli of the bile canaliculi were well preserved in the PFC group. For experiment II, the postoperative survival rate was significantly improved in the PFC group. In conclusion, graft preservation with PFC attenuated liver IRI and improved postoperative survival. This graft preservation protocol might be a new therapeutic option to improve the outcomes of DCD LT. Liver Transplantation 23 1171-1185 2017 AASLD.


Asunto(s)
Fluorocarburos/uso terapéutico , Trasplante de Hígado/efectos adversos , Soluciones Preservantes de Órganos/uso terapéutico , Preservación de Órganos/métodos , Daño por Reperfusión/prevención & control , Isquemia Tibia/efectos adversos , Adenosina/química , Adenosina/uso terapéutico , Aloinjertos/patología , Alopurinol/química , Alopurinol/uso terapéutico , Animales , Modelos Animales de Enfermedad , Fluorocarburos/química , Glutatión/química , Glutatión/uso terapéutico , Supervivencia de Injerto/efectos de los fármacos , Humanos , Insulina/química , Insulina/uso terapéutico , Hígado/patología , Pruebas de Función Hepática , Trasplante de Hígado/mortalidad , Masculino , Soluciones Preservantes de Órganos/química , Perfusión/métodos , Periodo Posoperatorio , Rafinosa/química , Rafinosa/uso terapéutico , Ratas , Ratas Endogámicas Lew , Daño por Reperfusión/sangre , Daño por Reperfusión/etiología , Daño por Reperfusión/patología , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento
15.
J Org Chem ; 82(2): 1024-1033, 2017 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-28004580

RESUMEN

A CuCl-catalyzed Ullmann-type C-N cross-coupling reaction of carbazoles and 2-bromopyridine derivatives has been developed for the synthesis of N-heteroarylcarbazole derivatives employing 1-methyl-imidazole and t-BuOLi as ligand and base, respectively, both of which are found to significantly promote the reaction. Low cost and low loading of both catalyst and ligand, together with high reaction yields, render this practical reaction to be suitable for large-scale preparations and could be useful in material science.

16.
J Org Chem ; 82(16): 8634-8644, 2017 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-28759993

RESUMEN

An efficient and practical CuCl-catalyzed hydroxylation of N-heteroarylcarbazole bromide for the preparation of N-heteroarylcarbazolyl phenols with a broad functional group scope and yield up to 98% was developed. It was found that both the ligand and base played critical roles in the functional group transformation and that different products could be generated by changing the base for some substrates. t-BuONa was demonstrated to be a better base for the catalytic system to avoid the formation of the ether byproduct. In addition, this approach was suitable for large-scale preparation and was successfully applied in the gram-scale synthesis of phosphorescent emitters PtNON and PdNON, demonstrating its practicability in organic synthesis methodology and materials science. Furthermore, the X-ray crystal diffraction, DFT calculations, and photophysical properties were also investigated for the metal complexes.

17.
Liver Transpl ; 22(9): 1231-44, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27102080

RESUMEN

Polyamines are essential for cell growth and differentiation. They play important roles in protection from liver damage and promotion of liver regeneration. However, little is known about the effect of oral exogenous polyamine administration on liver damage and regeneration. This study investigated the impact of polyamines (spermidine and spermine) on ischemia/reperfusion injury (IRI) and liver regeneration. We used a rat model in which a 70% hepatectomy after 40 minutes of ischemia was performed to mimic the clinical condition of living donor partial liver transplantation (LT). Male Lewis rats were separated into 2 groups: a polyamine group given polyamines before and after operation as treatment and a vehicle group given distilled water as placebo. The levels of serum aspartate aminotransferase and alanine aminotransferase at 6, 24, and 48 hours after reperfusion were significantly lower in the polyamine group compared with those in the vehicle group. Polyamine treatment reduced the expression of several proinflammatory cytokines and chemokines at 6 hours after reperfusion. Histological analysis showed significantly less necrosis and apoptosis in the polyamine group at 6 hours after reperfusion. Sinusoidal endothelial cells were also well preserved in the polyamine group. In addition, the regeneration of the remnant liver at 24, 48, and 168 hours after reperfusion was significantly accelerated, and the Ki-67 labeling index and the expressions of proliferating cell nuclear antigen and phosphorylated retinoblastoma protein at 24 hours after reperfusion were significantly higher in the polyamine group compared with those in the vehicle group. In conclusion, perioperative oral polyamine administration attenuates liver IRI and promotes liver regeneration. It might be a new therapeutic option to improve the outcomes of partial LT. Liver Transplantation 22 1231-1244 2016 AASLD.


Asunto(s)
Regeneración Hepática/efectos de los fármacos , Trasplante de Hígado/efectos adversos , Daño por Reperfusión/prevención & control , Espermidina/uso terapéutico , Espermina/uso terapéutico , Administración Oral , Alanina Transaminasa/sangre , Animales , Apoptosis/efectos de los fármacos , Aspartato Aminotransferasas/sangre , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Antígeno Ki-67/análisis , Hígado/patología , Trasplante de Hígado/métodos , Masculino , Necrosis/prevención & control , Antígeno Nuclear de Célula en Proliferación/análisis , Ratas , Ratas Endogámicas Lew , Daño por Reperfusión/sangre , Proteína de Retinoblastoma/análisis , Espermidina/administración & dosificación , Espermina/administración & dosificación
18.
Guang Pu Xue Yu Guang Pu Fen Xi ; 35(6): 1469-73, 2015 Jun.
Artículo en Zh | MEDLINE | ID: mdl-26601349

RESUMEN

With the development of nanotechnology, it has been accessible to display colors by artificial micro/nano-structure, and then the study of structure coloring has become a hot subject, opening a new space for inkless printing. In this paper, a dynamic color modulation method based on tunable micro/nano-structure array is proposed. To tune colors on the same device, a periodic micro/nano-structure array is designed with functional material inside, which could alter the height difference between up and bottom surface precisely by applying an external voltage. It is modeled, and simulated by the Finite Difference Time Domain (FDTD) method in this work. In simulations, perpendicular incident linearly polarized light source is applied, and parameters of surface height difference and period are swept. Series reflective spectra of the devices are obtained, and their corresponding colors are calculated and marked on the CIE 1931 chromaticity diagram. Simulation results demonstrate that when the period is in the range of 100-300 nm, full-color modulation could be realized by varying the height of functional material film via applied voltage, and the peak intensities of reflective spectra are at about 60%, having high energy efficiency. This method is innovative and provides a theoretical basis for the dynamic color modulation micro/nano device, which is quite promising in fields like inkless printing and display technology.

19.
J Food Sci Technol ; 52(12): 7588-98, 2015 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-26604336

RESUMEN

Glycerol contributes to the beverage body and fullness. Moreover, it also influences the flavor intensity. As a major byproduct, glycerol not only serves critical roles in yeast osmoregulation and redox balancing, but also acts as the carbon competitor against ethanol in alcoholic fermentation. Therefore, increasing glycerol yield benefits both the flavor and ethanol reduction for the fermented beverages. Glycerol yield has been elevated either by fermentation optimization or by yeast genetic modification. The fermentation optimizations reached maximum 14 g/L glycerol through screening yeast strains and optimizing fermentation parameters. Meanwhile the yeast overexpressing GPD1 (encoding glycerol-3-phosphate dehydrogenase) produced up to 6 folds more glycerol for beer and wine. Except for glycerol improvement, the genetically modified yeasts accumulated dramatically undesirable compounds such as acetaldehyde, acetate and acetoin which are detrimental for beverage flavor. In comparison, the natural high glycerol producers showed strain-specific manner on the yeast-derived aroma compounds like volatile acids, fusel alcohols, esters, and aldehydes. Temperature, sugar concentration, nitrogen composition, oxygen and pH-value, which influence glycerol biosynthesis, also obtained various effects on the production of aromatic compounds. In the current review, we firstly deliberate the organoleptic contributions of glycerol for fermented beverages. Furthermore, glycerol optimization strategies are discussed regarding to the yield improvement, the genes expressions, the overall flavor impacts and the feasibilities in beverage applications. Lastly, for improving beverage flavor by glycerol optimization, a high-throughput platform is proposed to increase the screening capacity of yeast strains and parameters in the processing of fermented beverages.

20.
Phytomedicine ; 130: 155711, 2024 Jul 25.
Artículo en Inglés | MEDLINE | ID: mdl-38749074

RESUMEN

BACKGROUND: Lignin has attracted a lot of attention because it is non-toxic, renewable and biodegradable. Lignin nanoparticles (LNPs) have high specific surface area and specific surface charges. It provides LNPs with good antibacterial and antioxidant properties. LNPs preparation has become clear, however, the application remains in the early stages. PURPOSE: A review centric research has been conducted, reviewing existing literature to accomplish a basic understanding of the medical applications of LNPs. METHODS: Initially, we extensively counseled the heterogeneity of lignin from various sources. The size and morphology of LNPs from different preparation process were then discussed. Subsequently, we focused on the potential medical applications of LNPs, including drug delivery, wound healing, tissue engineering, and antibacterial agents. Lastly, we explained the significance of LNPs in terms of antibacterial, antioxidant and biocompatibility, especially highlighting the need for an integrated framework to understand a diverse range of medical applications of LNPs. RESULTS: We outlined the chemical structure of different type of lignin, and highlighted the advanced methods for lignin nanoparticles preparation. Moreover, we provided an in-depth review of the potential applications of lignin nanoparticles in various medical fields, especially in drug carriers, wound dressings, tissue engineering components, and antimicrobial agents. CONCLUSION: This review provides a detailed overview on the current state and progression of lignin nanoparticles for medical applications.


Asunto(s)
Antibacterianos , Antioxidantes , Lignina , Nanopartículas , Lignina/química , Lignina/farmacología , Nanopartículas/química , Antioxidantes/farmacología , Antioxidantes/química , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/administración & dosificación , Humanos , Cicatrización de Heridas/efectos de los fármacos , Ingeniería de Tejidos/métodos , Portadores de Fármacos/química , Sistemas de Liberación de Medicamentos , Vendajes
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