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91.
92.
Aitor Benedicto I igo Garc a-Kamiruaga Beatriz Arteta 《World journal of gastroenterology : WJG》2021,27(24):3516-3529
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has a tremendous impact on the health of millions of people worldwide. Unfortunately, those suffering from previous pathological conditions are more vulnerable and tend to develop more severe disease upon infection with the new SARS-CoV-2. This coronavirus interacts with the angiotensin-converting enzyme 2 receptor to invade the cells. Recently, another receptor, neuropilin-1 (NRP-1), has been reported to amplify the viral infection. Interestingly, NRP-1 is expressed in nonparenchymal liver cells and is related to and upregulated in a wide variety of liver-related pathologies. It has been observed that SARS-CoV-2 infection promotes liver injury through several pathways that may be influenced by the previous pathological status of the patient and liver expression of NRP-1. Moreover, coronavirus disease 2019 causes an inflammatory cascade called cytokine storm in patients with severe disease. This cytokine storm may influence liver sinusoidal-cell phenotype, facilitating viral invasion. In this review, the shreds of evidence linking NRP-1 with liver pathologies such as hepatocellular carcinoma, liver fibrosis, nonalcoholic fatty liver disease and inflammatory disorders are discussed in the context of SARS-CoV-2 infection. In addition, the involvement of the infection-related cytokine storm in NRP-1 overexpression and the subsequent increased risk of SARS-CoV-2 infection are also analyzed. This review aims to shed some light on the involvement of liver NRP-1 during SARS-CoV-2 infection and emphasizes the possible involvement this receptor with the observed liver damage. 相似文献
93.
Most of ADP x glucose linked to starch biosynthesis occurs outside the chloroplast in source leaves 下载免费PDF全文
Baroja-Fernández E Muñoz FJ Zandueta-Criado A Morán-Zorzano MT Viale AM Alonso-Casajús N Pozueta-Romero J 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(35):13080-13085
Sucrose and starch are end products of two segregated gluconeogenic pathways, and their production takes place in the cytosol and chloroplast of green leaves, respectively. According to this view, the plastidial ADP.glucose (ADPG) pyrophosphorylase (AGP) is the sole enzyme catalyzing the synthesis of the starch precursor molecule ADPG. However, a growing body of evidences indicates that starch formation involves the import of cytosolic ADPG to the chloroplast. This evidence is consistent with the idea that synthesis of the ADPG linked to starch biosynthesis takes place in the cytosol by means of sucrose synthase, whereas AGP channels the glucose units derived from the starch breakdown. To test this hypothesis, we first investigated the subcellular localization of ADPG. Toward this end, we constructed transgenic potato plants that expressed the ADPG-cleaving adenosine diphosphate sugar pyrophosphatase (ASPP) from Escherichia coli either in the chloroplast or in the cytosol. Source leaves from plants expressing ASPP in the chloroplast exhibited reduced starch and normal ADPG content as compared with control plants. Most importantly however, leaves from plants expressing ASPP in the cytosol showed a large reduction of the levels of both ADPG and starch, whereas hexose phosphates increased as compared with control plants. No pleiotropic changes in photosynthetic parameters and maximum catalytic activities of enzymes closely linked to starch and sucrose metabolism could be detected in the leaves expressing ASPP in the cytosol. The overall results show that, essentially similar to cereal endosperms, most of the ADPG linked to starch biosynthesis in source leaves occurs in the cytosol. 相似文献
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95.
Restuccia T Gómez-Ansón B Guevara M Alessandria C Torre A Alayrach ME Terra C Martín M Castellví M Rami L Sainz A Ginès P Arroyo V 《Hepatology (Baltimore, Md.)》2004,39(6):1613-1622
In advanced cirrhosis there is a reduction in the brain concentration of many organic osmolytes, particularly myo-inositol (MI). Hyponatremia could theoretically aggravate these changes as a result of hypo-osmolality of the extracellular fluid. The aim of this study was to determine the effects of hyponatremia on brain organic osmolytes and brain water content in cirrhosis. Brain organic osmolytes, measured by (1)H-magnetic resonance spectroscopy, and brain water content, as estimated by magnetization transfer ratio (MTR) and measurement of brain volume were determined in 14 patients with dilutional hyponatremia, 10 patients without hyponatremia, and eight healthy subjects. Patients with hyponatremia had remarkable lower levels of MI compared with values in nonhyponatremic patients and healthy subjects. Brain MI levels correlated directly with serum sodium and osmolality. Serum sodium was the only independent predictor of low brain MI levels. Serum sodium also correlated directly with other brain organic osmolytes, such as choline-containing compounds, creatine/phosphocreatine, and N-acetyl-aspartate. By contrast, brain glutamine/glutamate levels were higher in patients with cirrhosis compared with values in healthy subjects and correlated with plasma ammonia levels but not with serum sodium or osmolality. No significant differences were found in MTR values and cerebral volumes between patients with and without hyponatremia. In conclusion, dilutional hyponatremia in cirrhosis is associated with remarkable reductions in brain organic osmolytes that probably reflect compensatory osmoregulatory mechanisms against cell swelling triggered by a combination of high intracellular glutamine and low extracellular osmolality. These findings may be relevant to the pathogenesis of encephalopathy in hyponatremic patients. 相似文献
96.
Small-molecule drugs that induce apoptosis in tumor cells by activation of the BCL-2-regulated mitochondrial outer membrane permeabilization (MOMP) pathway hold promise for rational anticancer therapies. Accumulating evidence indicates that the natural product gossypol and its derivatives can kill tumor cells by targeting antiapoptotic BCL-2 family members in such a manner as to trigger MOMP. However, due to the inherent complexity of the cellular apoptotic network, the precise mechanisms by which interactions between gossypol and individual BCL-2 family members lead to MOMP remain poorly understood. Here, we used simplified systems bearing physiological relevance to examine the impact of gossypol on the function of MCL-1, a key determinant for survival of various human malignancies that has become a highly attractive target for anticancer drug design. First, using a reconstituted liposomal system that recapitulates basic aspects of the BCL-2-regulated MOMP pathway, we demonstrate that MCL-1 inhibits BAX permeabilizing function via a “dual-interaction” mechanism, while submicromolar concentrations of gossypol reverse MCL-1-mediated inhibition of functional BAX activation. Solution-based studies showed that gossypol competes with BAX/BID BH3 ligands for binding to MCL-1 hydrophobic groove, thereby providing with a mechanistic explanation for how gossypol restores BAX permeabilizing function in the presence of MCL-1. By contrast, no evidence was found indicating that gossypol transforms MCL-1 into a BAX-like pore-forming molecule. Altogether, our findings validate MCL-1 as a direct target of gossypol, and highlight that making this antiapoptotic protein unable to inhibit BAX-driven MOMP may represent one important mechanism by which gossypol exerts its cytotoxic effect in selected cancer cells. 相似文献
97.
Christos Tapeinos Aitor Larrañaga Jose-Ramon Sarasua Abhay Pandit 《Nanomedicine : nanotechnology, biology, and medicine》2018,14(7):2397-2405
Excess reactive oxygen species (ROS) has been implicated in numerous diseases including cancer, cardiovascular and neurodegenerative diseases. Overexpression of ROS can lead to oxidative stress and subsequently to H2O2-mediated cell apoptosis. In this study, it was demonstrated that biodegradable PLGA microspheres coated with collagen type I and decorated with MnO2 nanoparticles acted as ROS scavengers controlling the H2O2-mediated apoptosis of cells undergoing oxidative stress. The results showed that the functionalized collagen spheres can protect cells even under very harsh conditions of oxidative stress. 相似文献
98.
99.
Laura Visa Paula Jiménez-Fonseca Elena Asensio Martínez Raquel Hernández Ana Custodio Manuel Garrido Antonio Viudez Elvira Buxo Ignacio Echavarria Juana María Cano Ismael Macias Montserrat Mangas Eva Martínez de Castro Teresa García Felipe Álvarez Manceñido Ana Fernández Montes Aitor Azkarate Federico Longo Alberto Carmona-Bayonas 《Journal of Geriatric Oncology》2018,9(3):254-264
Objective
Advanced gastric cancer (AGC) is a common neoplasm in older adults. Nevertheless, there are few specific management data in the literature. The aim of this study was to assess non-inferiority of survival and efficacy-related outcomes of chemotherapy used in older vs non-older patients with AGC.Materials and Methods
We recruited 1485 patients from the AGAMENON registry of AGC treated with polychemotherapy between 2008–2017. A statistical analysis was conducted to prove non-inferiority for overall survival (OS) associated with the use of chemotherapy schedules in individuals ≥ 70 vs.<70 years. The fixed-margin method was used (hazard ratio [HR]<1.176) that corresponds to conserving at least 85% efficacy. Results: 33% (n = 489) of the cases analyzed were ≥ 70 years. Two-agent chemotherapies and combinations with oxaliplatin (48% vs. 29%) were used more often in the older patients, as were modified schedules and/or lower doses. Toxicity grade 3–4 was comparable in both groups, although when looking at any grade, there were more episodes of enteritis, renal toxicity, and fatigue in older patients. In addition, toxicity was a frequent cause for discontinuing treatment in older patients. The response rate was similar in both groups. After adjusting for confounding factors, the non-inferiority of OS associated with schedules administered to the older vs. younger subjects was confirmed: HR 1.02 (90% CI, 0.91–1.14), P (non inferiority) = 0.018, as well as progression-free survival: HR 0.97 (90% CI, 0.87–1.08), P(non-inferiority) = 0.001.Conclusion
In this AGC registry, the use of chemotherapy with schedules adapted to patients ≥ 70 years provided efficacy that was not inferior to that seen in younger cases, with comparable adverse effects. 相似文献100.
Aitor Piedra Toni Caparrs Jordi Vicens-Bordas Javier Pea 《Journal of Sports Science and Medicine》2021,20(4):751
Data related to 141 sessions of 10 semi-professional basketball players were analyzed during the competitive period of the 2018-2019 season using a multivariable model to determine possible associations between internal and external load variables and fatigue. Age, height, weight, sessional rate of perceived exertion (sRPE), summated-heart-rate-zones, heart rate variability, total accelerations and decelerations were the covariates, and post-session countermovement jump loss (10% or higher) the response variable. Based on the results observed, a rise in sRPE and accelerations and decelerations could be associated with increased lower-body neuromuscular fatigue. Observing neuromuscular fatigue was 1,008 times higher with each additional sRPE arbitrary unit (AU). Each additional high-intensity effort also increased the probability of significant levels of neuromuscular fatigue by 1,005 times. Fatigue arising from demanding sporting activities is acknowledged as a relevant inciting event leading to injuries. Thus, the methodology used in this study can be used then to monitor neuromuscular fatigue onset, also enhancing proper individual adaptations to training. Key points
- Several internal and external load variables show associations with an increase in local neuromuscular fatigue detected through the countermovement jump test.
- Our main findings show promising results detecting the lower-body neuromuscular fatigue originated by specific training through and ecological, practical, and low time-consuming methodology. The proposed method can outline the players’ physiological state and inform decisions regarding the application of different training loads within a complex setting and multi-factorial process.