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1.
Neurol Sci ; 45(6): 2719-2728, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38150131

RESUMEN

OBJECTIVES: Patients with severe stroke are at high risk of developing acute respiratory distress syndrome (ARDS), but this severe complication was often under-diagnosed and rarely explored in stroke patients. We aimed to investigate the prevalence, early predictors, and outcomes of ARDS in severe stroke. METHODS: This prospective study included consecutive patients admitted to neurological intensive care unit (neuro-ICU) with severe stroke, including acute ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. The incidence of ARDS was examined, and baseline characteristics and severity scores on admission were investigated as potential early predictors for ARDS. The in-hospital mortality, length of neuro-ICU stay, the total cost in neuro-ICU, and neurological functions at 90 days were explored. RESULTS: Of 140 patients included, 35 (25.0%) developed ARDS. Over 90% of ARDS cases occurred within 1 week of admission. Procalcitonin (OR 1.310 95% CI 1.005-1.707, P = 0.046) and PaO2/FiO2 on admission (OR 0.986, 95% CI 0.979-0.993, P < 0.001) were independently associated with ARDS, and high brain natriuretic peptide (OR 0.994, 95% CI 0.989-0.998, P = 0.003) was a red flag biomarker warning that the respiratory symptoms may be caused by cardiac failure rather than ARDS. ARDS patients had longer stays and higher expenses in neuro-ICU. Among patients with ARDS, 25 (62.5%) were moderate or severe ARDS. All the patients with moderate to severe ARDS had an unfavorable outcome at 90 days. CONCLUSIONS: ARDS is common in patients with severe stroke, with most cases occurring in the first week of admission. Procalcitonin and PaO2/FiO2 on admission are early predictors of ARDS. ARDS worsens both short-term and long-term outcomes. The conflict in respiratory support strategies between ARDS and severe stroke needs to be further studied.


Asunto(s)
Síndrome de Dificultad Respiratoria , Accidente Cerebrovascular , Humanos , Síndrome de Dificultad Respiratoria/epidemiología , Síndrome de Dificultad Respiratoria/complicaciones , Masculino , Femenino , Anciano , Estudios Prospectivos , Prevalencia , Persona de Mediana Edad , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/complicaciones , Unidades de Cuidados Intensivos/estadística & datos numéricos , Índice de Severidad de la Enfermedad , Mortalidad Hospitalaria , Anciano de 80 o más Años , Tiempo de Internación/estadística & datos numéricos
2.
Biomed Chromatogr ; 38(1): e5763, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37858975

RESUMEN

Alisol B 23-acetate (AB23A) has been demonstrated to have beneficial effects on nonalcoholic steatohepatitis (NASH). However, the mechanisms of AB23A on NASH remain unclear. This study aimed to investigate the mechanisms underlying the metabolic regulatory effects of AB23A on NASH. We used AB23A to treat mice with NASH, which was induced by a methionine and choline deficient (MCD) diet. We initially investigated therapeutic effect and resistance to oxidation and inflammation of AB23A on NASH. Subsequently, we performed untargeted metabolomic analyses and relative validation assessments to evaluate the metabolic regulatory effects of AB23A. AB23A reduced lipid accumulation, ameliorated oxidative stress and decreased pro-inflammatory cytokines in the liver. Untargeted metabolomic analysis found that AB23A altered the metabolites of liver. A total of 55 differential metabolites and three common changed pathways were screened among the control, model and AB23A treatment groups. Further tests validated the effects of AB23A on modulating common changed pathway-involved factors. AB23A treatment can ameliorate NASH by inhibiting oxidative stress and inflammation. The mechanism of AB23A on NASH may be related to the regulation of alanine, aspartate and glutamate metabolism, d-glutamine and d-glutamate metabolism, and arginine biosynthesis pathways.


Asunto(s)
Enfermedad del Hígado Graso no Alcohólico , Ratones , Animales , Enfermedad del Hígado Graso no Alcohólico/metabolismo , Metionina/metabolismo , Metionina/farmacología , Colina , Hígado/metabolismo , Racemetionina/metabolismo , Racemetionina/farmacología , Dieta , Inflamación/metabolismo , Ratones Endogámicos C57BL , Modelos Animales de Enfermedad
3.
J Am Chem Soc ; 145(16): 9129-9135, 2023 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-37053567

RESUMEN

Although alcohols are readily oxidized by a variety of oxidants, their oxidation by metal nitrido complexes is yet to be studied. We report herein visible-light-induced oxidation of primary and secondary alcohols to carbonyl compounds by a strongly luminescent osmium(VI) nitrido complex (OsN). The proposed mechanism involves initial rate-limiting hydrogen-atom transfer (HAT) from the α-carbon of the alcohol to OsN*. Attempts to develop catalytic oxidation of alcohols by OsN* using PhIO as the terminal oxidant resulted in the formation of novel osmium(IV) iminato complexes in which the nitrido ligand is bonded to a δ-carbon of the alcohol. Experimental and theoretical studies suggest that OsN* is reductively quenched by PhIO to generate PhIO+, which is a highly active oxidant that readily undergoes α- and δ-C-H activation of alcohols.

4.
J Org Chem ; 88(9): 5801-5812, 2023 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-37053546

RESUMEN

3-Amino oxindole Schiff base has been used as an efficient and crucial synthon for highly enantioselective benzylation and allylation with benzyl bromides and allyl bromides in the presence of a 1,3-bis[O(9)-allylcinchonidinium-N-methyl]-2-fluorobenzene dibromide phase transfer catalyst under mild reaction conditions. A broad series of chiral quaternary 3-amino oxindoles were smoothly obtained in good to excellent yields with excellent enantioselectivities (up to 98% ee) with broad substrate generality. A typical scale-up preparation and subsequent Ullman coupling reaction were also smoothly performed, and a special and important chiral spirooxindole benzofuzed pyrrol scaffold with potential pharmaceutical and organocatalytic activities was successfully obtained.

5.
Inorg Chem ; 62(4): 1447-1454, 2023 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-36633522

RESUMEN

The reactivity of electrophilic OsVI and RuVI nitrides toward various aliphatic and aromatic amines have been previously reported; these reactions all go through an initial nucleophilic addition of the amine nitrogen to MVI≡N (M = Os, Ru) to generate a MIV hydrazido species. Herein, we report that the excited state of a luminescent osmium(VI) nitrido complex, [OsVI(N)(L)(CN)3]- (OsN, HL = 2-(2-hydroxy-5-nitrophenyl)benzoxazole), undergoes unprecedented ring nitrogenation of aromatic amines. Visible-light irradiation of OsN generates OsN*, which predominantly attacks the aromatic ring of 2,6-dimethylaniline (Me2PhNH2) to give an Os(II) benzoquinone diimine compound (PPh4)[OsII(L)(CN)3(p-NH═Me2Ph═NH2)] [(PPh4)2] in 60% yield, while nucleophilic addition of the amine N to OsN* also occurs to give the osmium(II) diazonium compound (PPh4)[OsII(L)(CN)3(N = N-Me2Ph)] [(PPh4)1] as a minor product (10% yield). On the other hand, OsN* undergoes exclusive ring nitrogenation of diphenylamine, indole, and carbazole to give the corresponding osmium(II) benzoquinone diimines. All products have been characterized by various spectroscopic techniques and by X-ray crystallography. The reaction between OsN* and Ar2N is proposed to proceed via an initial 1e- transfer (ET) followed by proton transfer (PT) to generate OsVNH and Ar2N• intermediates, which then further combine to give the product. The benzoquinone diimine ligands are susceptible to oxidation. Oxidation of 2 with H2O2 at ambient conditions affords [OsIV(L)(CN)3(N═PhMe2(O)═O)]-, which bears the previously unknown (epoxy)benzoquinone iminato ligand.

6.
Acta Pharmacol Sin ; 44(1): 189-200, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35778489

RESUMEN

The high incidence of lymphatic metastasis is closely related to poor prognosis and mortality in cancers. Potent inhibitors to prevent pathological lymphangiogenesis and lymphatic spread are urgently needed. The VEGF-C-VEGFR3 pathway plays a vital role in driving lymphangiogenesis and lymph node metastasis. In addition, COX2 in tumor cells and tumor-associated macrophages (TAMs) facilitates lymphangiogenesis. We recently reported that aiphanol, a natural stilbenolignan, attenuates tumor angiogenesis by repressing VEGFR2 and COX2. In this study, we evaluated the antilymphangiogenic and antimetastatic potency of aiphanol using in vitro, ex vivo and in vivo systems. We first demonstrated that aiphanol directly bound to VEGFR3 and blocked its kinase activity with an half-maximal inhibitory concentration (IC50) value of 0.29 µM in an in vitro ADP-GloTM kinase assay. Furthermore, we showed that aiphanol (7.5-30 µM) dose-dependently counteracted VEGF-C-induced proliferation, migration and tubular formation of lymphatic endothelial cells (LECs), which was further verified in vivo. VEGFR3 knockdown markedly mitigated the inhibitory potency of aiphanol on lymphangiogenesis. In 4T1-luc breast tumor-bearing mice, oral administration of aiphanol (5 and 30 mg· kg-1 ·d-1) dose-dependently decreased lymphatic metastasis and prolonged survival time, which was associated with impaired lymphangiogenesis, angiogenesis and, interestingly, macrophage infiltration. In addition, we found that aiphanol decreased the COX2-dependent secretion of PGE2 and VEGF-C from tumor cells and macrophages. These results demonstrate that aiphanol is an appealing agent for preventing lymphangiogenesis and lymphatic dissemination by synergistically targeting VEGFR3 and inhibiting the COX2-PGE2-VEGF-C signaling axis.


Asunto(s)
Linfangiogénesis , Factor C de Crecimiento Endotelial Vascular , Animales , Ratones , Línea Celular Tumoral , Ciclooxigenasa 2/metabolismo , Dinoprostona/metabolismo , Células Endoteliales/metabolismo , Metástasis Linfática , Factor C de Crecimiento Endotelial Vascular/metabolismo
7.
J Nanobiotechnology ; 21(1): 467, 2023 Dec 07.
Artículo en Inglés | MEDLINE | ID: mdl-38062518

RESUMEN

Tumor cell-released LC3+ extracellular vesicles (LC3+ EVs) participate in immunosuppression during autophagy and contribute to the occurrence and development of breast cancer. In view of the strong association between the LC3+ EVs and breast cancer, developing an effective strategy for the quantitative detection of LC3+ EVs levels with high sensitivity to identify LC3+ EVs as new biomarkers for accurate diagnosis of breast cancer is crucial, but yet not been reported. Herein, an ultrasensitive electrochemical immunosensor is presented for the quantitative determination of LC3+ EVs using a three-dimensional graphene oxide hydrogel-methylene blue composite as a redox probe, showing a low detection limit and a wide linear range. With this immunosensor, the expression levels of LC3+ EVs in various practical sample groups including different cancer cell lines, the peripheral blood of tumor-bearing mice before and after immunotherapy, and the peripheral blood from breast cancer patients with different subtypes and stages were clearly distinguished. This study demonstrated that LC3+ EVs were superior as biomarkers for the accurate diagnosis of breast cancer compared to traditional biomarkers, particularly for cancer subtype discrimination. This work would provide a new noninvasive detection tool for the early diagnosis and prognosis assessment of breast cancer in clinics.


Asunto(s)
Técnicas Biosensibles , Neoplasias de la Mama , Vesículas Extracelulares , Humanos , Animales , Ratones , Femenino , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/metabolismo , Hidrogeles , Biomarcadores de Tumor/metabolismo , Inmunoensayo/métodos , Biomarcadores/metabolismo , Vesículas Extracelulares/metabolismo
8.
Gen Comp Endocrinol ; 330: 114149, 2023 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-36336108

RESUMEN

Melanocortin-3 receptor (MC3R) not only regulates energy homeostasis in animals, but also is an important regulator of inflammation. As one of the most widely farmed freshwater fish, common carp has attracted great interest for its feeding and inflammation regulation. In this study, we cloned the coding sequence (CDS) of common carp Mc3r (ccMc3r), examined its tissue expression profile, and investigated the function of this receptor in mediating downstream signaling pathways. The results showed that the CDS of ccMc3r was 975 bp, encoding a putative protein of 324 amino acids. Homology, phylogeny, and chromosomal synteny analyses revealed that ccMc3r is evolutionarily close to the orthologs of cyprinids. Quantitative real-time PCR (qPCR) indicated that ccMc3r was highly expressed in the brain and intestine. The luciferase reporter systems showed that four ligands, ACTH (1-24), α-MSH, ß-MSH, and NDP-MSH, were able to activate the cAMP and MAPK/ERK signaling pathways downstream of ccMc3r with different potencies. For the cAMP signaling pathway, ACTH (1-24) had the highest activation potency; while for the MAPK/ERK signaling pathway, ß-MSH had the greatest activation effect. In addition, we found that the four agonists were able to inhibit TNF-α-induced NF-κB signaling in approximately the same order of potency as cAMP signaling activation. This study may facilitate future studies on the role of Mc3r in common carp feed efficiency and immune regulation.


Asunto(s)
Carpas , Receptor de Melanocortina Tipo 3 , Animales , Distribución Tisular , Receptor de Melanocortina Tipo 3/genética , Carpas/genética , beta-MSH , Cosintropina , Clonación Molecular
9.
BMC Musculoskelet Disord ; 24(1): 364, 2023 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-37161368

RESUMEN

BACKGROUND: Currently, there is no consensus on the most appropriate technique for obtaining lateral hip radiographs after cephalomedullary nail (CMN) surgery. The aim of this study was to investigate the distribution of two commonly used postoperative lateral hip radiographic methods (classic lateral view and modified lateral view) and try to find out which one is better suited for this situation. METHODS: A retrospective analysis was conducted on 146 patients who underwent surgical fixation for extracapsular hip fractures between January 2018 and June 2022. The main outcome measured was the angle between the straight part of the CMN and the lag screw/blade on hip lateral X-rays (CMNA). The lateral hip radiographs were categorized into two groups based on different lateral hip radiographic methods. CMNA, patient age, gender, fracture classification based on the 2018 AO classification, nail length (short/long), surgical side (left/right), height, weight, BMI, preoperative waiting time, postoperative imaging interval were collected and compared between the two groups. RESULTS: The distribution trend of CMNA significantly differs between two types of hip joint lateral radiographic methods. Specifically, the classic lateral method exhibits a significantly bimodal and skewed distribution with a median (p25, p75) of -21.6° (-31.2°, -8°), whereas the modified lateral method presents a normal distribution with a mean ± SD of +7.57° ± 14.4°. The difference in the Mean Rank between the classic (47.10) and the modified (102.96) lateral methods is statistically significant (P < 0.001). CONCLUSIONS: The CMNA method is an excellent tool for studying the lateral distribution.We recommend using the modified lateral view as the preferred option for obtaining lateral hip radiographs after CMN surgery due to its superior distribution of CMNA and greater patient-friendliness.


Asunto(s)
Tornillos Óseos , Fracturas de Cadera , Humanos , Estudios Retrospectivos , Radiografía , Cuidados Posoperatorios , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/cirugía
10.
Fish Physiol Biochem ; 49(1): 61-74, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36525144

RESUMEN

Melanocortin 3 and 4 receptors are two important neural G protein-coupled receptors that regulate energy homeostasis in vertebrates. Melanocortin receptor accessory protein 2 (MRAP2) is also involved in the regulation of food intake and body weight as a variable regulator of melanocortin receptors. Rainbow trout (Oncorhynchus mykiss) is a valuable cold-water fish cultured worldwide. In the rainbow trout model, we cloned and identified mrap2a, a paralog of mrap2. Rainbow trout mrap2a consisted of a 690 bp ORF and was expected to encode a putative protein of 229 amino acids. The qPCR results showed that rainbow trout mrap2a was expressed at high levels in brain tissue similar to mc3r and mc4r. In addition, co-immunoprecipitation verified that MRAP2a interacts with MC3R and MC4R in vitro and that MRAP2a is involved in and regulates the constitutive activity and signaling of MC3R and MC4R. MRAP2a reduced constitutive and agonist-stimulated cAMP levels of MC3R; furthermore, MRAP2a increased constitutive ERK1/2 activation but reduced ligand-induced stimulation at high levels of expression. For MC4R, MRAP2a showed decreased cAMP basal activity but increased agonist-stimulated cAMP signaling and increased ACTH ligand sensitivity. However, MRAP2a failed to affect MC4R constitutive activity and agonist-induced ERK1/2 signaling. Undoubtedly, our study will have great significance for revealing the conserved role of MC4R and MC3R signaling in teleost fish, especially in cold-water fish growth and energy homeostasis.


Asunto(s)
Oncorhynchus mykiss , Animales , Oncorhynchus mykiss/genética , Ligandos , Receptores de Melanocortina , Transducción de Señal , Peso Corporal
11.
BMC Plant Biol ; 22(1): 85, 2022 Feb 25.
Artículo en Inglés | MEDLINE | ID: mdl-35216546

RESUMEN

BACKGROUND: For better understanding the mechanism of Reaumuria soongarica community formation in a salt stressed grassland ecosystem, we designed a field experiment to test how leaves salt secretion changes the competitive relationship between species in this plant communities. RESULTS: Among the three species (R. soongarica, Stipa glareosa and Allium polyrhizum) of the salt stressed grassland ecosystem, the conductivity of R. soongarica rhizosphere soil was the highest in five soil layers (0-55 cm depth). The high soil conductivity can increase the daily salt secretion rate of plant leaves of R. soongarica. In addition, we found the canopy size of R. soongarica was positively related to the distance from S. glareosa or A. polyrhizum. The salt-tolerance of R. soongarica was significantly higher than the other two herbs (S. glareosa and A. polyrhizum). Moreover, there was a threshold (600 µS/cm) for interspecific competition of plants mediated by soil conductivity. When the soil conductivity was lower than 600 µS/cm, the relative biomass of R. soongarica increased with the soil conductivity increase. CONCLUSIONS: The efficient salt secretion ability of leaves increases soil conductivity under the canopy. This leads the formation of a "saline island" of R. soongarica. Meanwhile R. soongarica have stronger salt tolerance than S. glareosa and A. polyrhizum. These promote the competitiveness of R. soongarica and inhibit interspecies competition advantage of the other two herbs (S. glareosa and A. polyrhizum) in the plant community. It is beneficial for R. soongarica to establish dominant communities in saline regions of desert grassland.


Asunto(s)
Hojas de la Planta/metabolismo , Sales (Química)/metabolismo , Tamaricaceae/fisiología , Allium/fisiología , China , Clima Desértico , Pradera , Poaceae/fisiología , Rizosfera , Salinidad , Tolerancia a la Sal , Suelo/química , Tamaricaceae/crecimiento & desarrollo
12.
Inorg Chem ; 61(42): 16831-16840, 2022 Oct 24.
Artículo en Inglés | MEDLINE | ID: mdl-36228087

RESUMEN

A series of luminescent Pb2+ complexes, [Pb(L1)2]n (1), [Pb(L2)2]n (2), [Pb(L3)(NO3)(H2O)2]n (3), [Pb(L3)(Br)(H2O)]n (4), [Pb(L3)(Cl)(H2O)]n (5), and [Pb(L4)(H2O)2] (6) have been synthesized by treatment of polydentate tetrazolato ligands with various hydrated Pb2+ salts (HL1 = 2-(1H-tetrazol-5-yl)pyridine, HL2 = 3-(1H-tetrazol-5-yl)isoquinoline, HL3 = 6-(1H-tetrazol-5-yl)-2,2'-bipyridine, and H2L4 = 6,6'-bis(1H-tetrazol-5-yl)-2,2'-bipyridine). These complexes have been characterized by IR, TGA, and elemental analysis. Their crystal structures have been determined by X-ray crystallography, and the phase purity of bulk samples were further confirmed by PXRD. Their luminescence properties have been investigated in detail, and their emission origin may involve ligand-centered π-π* transition, metal-centered s-p transition and charge-transfer character. It is interesting to note that 5 exhibits obviously enhanced red-shifted emission, whose photoluminescence quantum yield (PLQY = 16.5%) is much higher than the other compounds (≤2%). Most importantly, the emission property of 5 was strongly affected by temperature. When the temperature rises from 295 to 493 K, the emission maximum gradually shifts to high energy due to the loss of the aqua ligand. In contrast, when the temperature is lowered from 295 to 13 K, two emission bands were observed. The low-energy emission band exhibits a slight blue shift, while a new high-energy emission band appears at around 520 nm, which is assigned to ligand-centered phosphorescence. After removal of the coordinated aqua ligand, the emission of 5-H2O is very sensitive to the vapors of volatile primary amines and acids, although they have different response mechanisms. This result indicates that 5-H2O may be a potential multifunctional sensor for temperature, volatile amines, and acids. To decipher the emission origin, DFT calculations have also been carried out based on the structure units of these compounds.

13.
Vascular ; 30(5): 977-987, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34455818

RESUMEN

OBJECTIVES: Various inflammatory factors are closely associated with the incidence of thoracic aortic aneurysms (TAAs). Furthermore, the severity of inflammation is closely related to the absolute value and proportion of each leukocyte subgroup. Only few reports have analyzed the importance of lymphocyte-monocyte ratio (LMR) as a potential inflammatory marker in vascular diseases. Therefore, we aimed to investigate the effect of peripheral blood LMR on thoracic endovascular aortic repair (TEVAR) in patients with TAA. METHODS: A retrospective study of the clinical data collected in our hospital between January 2016 and January 2021 was performed on 162 patients with TAA treated with TEVAR, based on the inclusion and exclusion criteria for patient selection. Based on whether the patient had the clinical symptoms at admission and the occurrence of type I endoleaks during operation, patients were divided into two groups, respectively: an intraoperative type I endoleak group (n = 34) and a group without intraoperative type I endoleak (n = 128), and a group with clinical symptoms (n = 31) and a group without clinical symptoms (n = 131). The clinical data of these two groups were compared, the free from second intervention rates related to endoleak and the preoperatively LMR of the two groups was calculated. LMR was calculated preoperatively. Receiver-operating characteristic curve analysis was used to determine the cut-off for preoperative LMR values. Based on the cut-off point, patients were divided into a high LMR group (n = 34) and a low LMR group (n = 128). The clinical data of the two groups were compared, and further stratified analysis was performed. RESULTS: A total of 162 patients were included in the analysis. All patients were successfully implanted with a thoracic aorta stent graft. The preoperative LMR level and postoperative endoleak-related secondary intervention rate were higher in the type I endoleak group than those in the group without intraoperative type I endoleaks. The preoperative C-reactive protein (CRP) level of patients with TAA with clinical symptoms was higher than that of asymptomatic patients. There was a negative correlation between preoperative CRP and LMR levels. In addition, in symptomatic or asymptomatic patients, the LMR level was associated with the occurrence of intraoperative type I endoleaks. After excluding the influence of type of endografts, our results showed that the clinical symptoms did not affect the occurrence of the intraoperative type I endoleak, and patients with intraoperative type I endoleak had a higher rate of postoperative secondary intervention. CONCLUSION: Patients with TAA with type I endoleaks during TEVAR had an increased rate of secondary intervention related to endoleaks. Patients with TAA with high LMR levels before TEVAR were more likely to have endoleaks during operation.


Asunto(s)
Implantación de Prótesis Vascular , Procedimientos Endovasculares , Aorta Torácica/cirugía , Prótesis Vascular/efectos adversos , Implantación de Prótesis Vascular/efectos adversos , Proteína C-Reactiva , Endofuga/diagnóstico por imagen , Endofuga/etiología , Endofuga/cirugía , Procedimientos Endovasculares/efectos adversos , Humanos , Linfocitos , Monocitos , Diseño de Prótesis , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Resultado del Tratamiento
14.
Fish Physiol Biochem ; 48(1): 241-252, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35098384

RESUMEN

The melanocortin-3 receptor (MC3R) is an important regulator of energy homeostasis and inflammation in mammals. However, its function in teleost fish needs to be further explored. In this study, we characterized rainbow trout MC3R (rtMC3R), which encoded a putative protein of 331 amino acids. Phylogenetic and chromosomal synteny analyses showed that rtMC3R was closely related to bony fishes. Quantitative PCR (qPCR) revealed that the transcripts of rtMC3R were highly expressed in the brain and muscle. The cellular function of rtMC3R was further verified by the signal-pathway-specific luciferase reporter assays. Four agonists such as α-MSH, ß-MSH, ACTH (1-24), and NDP-MSH can active rtMC3R, increasing the production of intracellular cAMP and upregulating MAPK/ERK signals. Moreover, we found that rtMC3R stimulated with α-MSH and NDP-MSH can significantly inhibit the NF-κB signaling pathway. This research will be helpful for further studies on the function of MC3R in rainbow trout, especially the role of energy metabolism and immune regulation.


Asunto(s)
Proteínas de Peces/genética , Oncorhynchus mykiss , Receptor de Melanocortina Tipo 3 , Secuencia de Aminoácidos , Animales , Oncorhynchus mykiss/genética , Filogenia , Receptor de Melanocortina Tipo 3/genética , alfa-MSH/farmacología
15.
Crit Rev Eukaryot Gene Expr ; 31(1): 1-9, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33639050

RESUMEN

We investigated expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) and endoglin (CD105) in renal cell carcinoma (RCC), and its potential role in predicting tumor growth and progression. A total of 47 RCC specimens and 15 adjacent normal kidney tissues were obtained. Expression of CEACAM1 and CD105 was assessed by immunohistochemistry. Microvessel density (MVD) was counted under the microscope by labeling the endothelial cells with biomarker CD34. The positivity of CEACAM1 expression in RCC (42.6%) was significantly lower than that in the normal kidney (73.%, P = 0.038). In contrast, the positivity of CD105 expression was significantly higher in RCC (78.7%) compared to that in the normal kidney (46.7%, P = 0.017). The expression level of CD105 in 47 RCC patients was significantly associated with the clinical stages of RCC (P < 0.05) but not with gender, age, tumor size, or histologic grade. Average MVD in RCC (78.05 ± 16.57) was significantly higher than that in normal tissue (43.62 ± 12.37, P < 0.05), and was significantly higher in RCC patients with advanced histologic grades (P < 0.05) or clinical stages (P < 0.01). In addition, MVD was significantly correlated with CD105 but negatively correlated with CEACAM1. Our findings suggest that down-regulation of CEACAM1 may promote angiogenesis in RCC, and that up-regulation of CD105 may promote RCC progress. MVD may be an indicator of RCC malignancy.


Asunto(s)
Antígenos CD/metabolismo , Carcinoma de Células Renales/metabolismo , Moléculas de Adhesión Celular/metabolismo , Endoglina/metabolismo , Regulación Neoplásica de la Expresión Génica , Neoplasias Renales/metabolismo , Densidad Microvascular , Antígenos CD34/metabolismo , Biomarcadores de Tumor/metabolismo , Carcinoma de Células Renales/patología , Progresión de la Enfermedad , Células Endoteliales/metabolismo , Células Endoteliales/patología , Femenino , Humanos , Inmunohistoquímica/métodos , Neoplasias Renales/genética , Neoplasias Renales/patología , Masculino , Neovascularización Patológica/metabolismo , Pronóstico
16.
Cancer Immunol Immunother ; 70(2): 463-474, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32809049

RESUMEN

Dendritic cell (DC) vaccine has been proved to be an effective way in cancer immunotherapy in both preclinical and clinical studies. However, limitations in DC isolation and culture have hampered its practice and promoted the development of other antigen-presenting cells (APCs) sources to fulfill that role. Our previous studies have shown that B cells loaded by tumor cell-derived autophagosomes, which we named as DRibbles (defective ribosomal products-containing blebs), could reactivate DC-induced effector T cell response. In this study, the roles of DRibble-loaded B cells in priming naïve CD8+ T cell responses and controlling tumors were investigated. We found that high-mobility group box 1 protein (HMGB1) on DRibbles was involved in DRibble-induced B cell activation, and the DRibble-triggered B cell phagocytosis via the caveolae-mediated endocytosis pathway. By using OT-I mouse-derived T cells, we demonstrated that DRibble-loaded B cells could activate specific naïve CD8+ T cells in vitro and ex vivo. In a tumor-bearing mouse model, DRibble-loaded B cells elicited systemic antitumor immunity and significantly suppressed the tumor growth. Moreover, the antitumor efficacy of DRibble-loaded B cells was enhanced when they were combined with CpG and anti-CD40 stimulation. These results suggest that DRibble-loaded B cells represent a viable and practical therapeutic vaccination strategy that might have important clinical implications for tumor immunotherapy.


Asunto(s)
Autofagosomas/inmunología , Linfocitos B/inmunología , Vacunas contra el Cáncer/uso terapéutico , Células Dendríticas/metabolismo , Inmunoterapia/métodos , Neoplasias/genética , Animales , Linfocitos T CD8-positivos/inmunología , Línea Celular Tumoral , Humanos , Ratones
17.
J Org Chem ; 86(23): 17371-17379, 2021 12 03.
Artículo en Inglés | MEDLINE | ID: mdl-34783555

RESUMEN

The spiro scaffold chiral organocatalyst of 3,2'-pyrrolidinyl spiro-oxindole amine was successfully prepared from racemic spiro-oxindole amine using l-menthol as a chiral pool in 4 steps in 28%-40% overall yields with at least 99% ee in scale-up preparation, and its catalytic activity was evaluated in the enantioselective aldol condensation between 3-(3-hydroxy-1H-pyrazol-1-yl)-oxindole and paraformaldehyde. The spiro organocatalyst showed superior catalytic activity and selectivity compared with its counterparts, and most substrates offered good to excellent results with up to 96% yield in 96% ee.


Asunto(s)
Compuestos de Espiro , Aldehídos , Aminas , Formaldehído , Indoles , Estructura Molecular , Oxindoles , Polímeros , Estereoisomerismo
18.
Org Biomol Chem ; 19(35): 7690-7694, 2021 09 15.
Artículo en Inglés | MEDLINE | ID: mdl-34524340

RESUMEN

A bifunctional cinchona squaramide catalyzed enantioselective aza-Friedel-Crafts reaction between 2-naphthols and benzothiazolimines has been developed, and a series of chiral 2'-aminobenzothiazolomethyl naphthols with potential antiproliferative and anthelmintic activities have been successfully and effectively prepared in good to excellent yields (up to 98%) with excellent enantioselectivities (up to >99% ee) even in a scale-up preparation under mild conditions.

19.
Sensors (Basel) ; 21(21)2021 Nov 03.
Artículo en Inglés | MEDLINE | ID: mdl-34770632

RESUMEN

Suffering from structural deterioration and natural disasters, the resilience of civil structures in the face of extreme loadings inevitably drops, which may lead to catastrophic structural failure and presents great threats to public safety. Earthquake-induced extreme loading is one of the major reasons behind the structural failure of buildings. However, many buildings in earthquake-prone areas of China lack safety monitoring, and prevalent structural health monitoring systems are generally very expensive and complicated for extensive applications. To facilitate cost-effective building-safety monitoring, this study investigates a method using cost-effective MEMS accelerometers for buildings' rapid after-earthquake assessment. First, a parameter analysis of a cost-effective MEMS sensor is conducted to confirm its suitability for building-safety monitoring. Second, different from the existing investigations that tend to use a simplified building model or small-scaled frame structure excited by strong motions in laboratories, this study selects an in-service public building located in a typical earthquake-prone area after an analysis of earthquake risk in China. The building is instrumented with the selected cost-effective MEMS accelerometers, characterized by a low noise level and the capability to capture low-frequency small-amplitude dynamic responses. Furthermore, a rapid after-earthquake assessment scheme is proposed, which systematically includes fast missing data reconstruction, displacement response estimation based on an acceleration response integral, and safety assessment based on the maximum displacement and maximum inter-story drift ratio. Finally, the proposed method is successfully applied to a building-safety assessment by using earthquake-induced building responses suffering from missing data. This study is conducive to the extensive engineering application of MEMS-based cost-effective building monitoring and rapid after-earthquake assessment.


Asunto(s)
Terremotos , Sistemas Microelectromecánicos , Aceleración , Acelerometría , Análisis Costo-Beneficio
20.
J Org Chem ; 85(5): 3921-3928, 2020 03 06.
Artículo en Inglés | MEDLINE | ID: mdl-31944112

RESUMEN

An abnormal [3 + 2]-cycloaddition and highly effective and convenient one-step preparation of tetracyclic bispirooxindoles containing two all-carbon quaternary spirocenters from isatin N,N'-cyclic azomethine imine 1,3-dipole and 3-methyleneoxindole in the presence of catalytic organic base has been disclosed. A variety of bispirooxindoles bearing a dinitrogen heterocycle with four adjacent cycles have been obtained in excellent yields (up to 95%) and diastereoselectivities (>99:1) under mild conditions.

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