RESUMEN

Muscle atrophy is a common complication of chronic kidney disease (CKD). Irisin, a novel muscle cytokine, protects against muscle atrophy, but its specific role in CKD-associated muscle atrophy requires further elucidation. Because the ubiquitin-proteasome system (UPS) plays an important role in CKD muscle atrophy, our study will explore whether irisin affects UPS and alleviate CKD-associated muscle atrophy. In this study, an adenine-fed mouse model of CKD and urotension II (UII)-induced C2C12 myotubes were used as in vivo and in vitro models of muscle atrophy. The results showed that renal function, mouse weight, and the cross-sectional area (CSA) of skeletal muscles were significantly improved in CKD mice treated with irisin. Moreover, irisin effectively mitigated the decreases in phosphorylated Forkhead box O 3a (p-FOXO3A) levels and increases in the levels of E3 ubiquitin ligases, such as muscle RING finger 1 (MuRF1) and muscle atrophy F-box (MAFbx/atrogin1), in both the muscles of CKD mice and UII-induced C2C12 myotubes. In addition, irisin significantly increased the expression levels of myogenic differentiation factor D (MyoD) in the muscles of CKD mice. Our study is the first to demonstrate that irisin ameliorates skeletal muscle atrophy by inhibiting UPS upregulation and improving satellite cell differentiation in CKD.

RESUMEN

Groundwater pollution risk evaluation is an important basis for developing groundwater protection measures and management strategies, and its accuracy directly affects the effectiveness of protection measures. The heterogeneity of the aquifer significantly affects the transport process of pollutants, increasing the uncertainty of pollutant risk assessment. However, in the actual site, borehole data that reveal aquifer heterogeneity are costly, and only a limited number of borehole data are available, which cannot accurately describe the heterogeneity of the aquifer, thus limiting the accuracy of groundwater pollution risk assessment. In order to overcome the above problems, this paper proposes a groundwater pollution risk assessment framework based on the stochastic and deterministic simulation of aquifer lithology. Based on the statistical characteristics of the change of lithology type in the actual borehole, the framework uses Markov chain to generate some sets of random lithology field and transforms them into heterogeneity parameter field, so as to realize the stochastic assessment of the pollution risk of groundwater resource wells. Furthermore, combined with the pumping test data, the parameter field that is most suitable for the actual situation is selected to evaluate the pollution risk deterministically. Finally, the stochastic and deterministic results are combined to comprehensively evaluate the pollution risk of groundwater resource wells. Through a case study in a river valley plain, the feasibility of the above framework is verified, and good application effects are achieved. This study provides a feasible method for accurately assessing groundwater pollution risk, which is helpful to reduce the impact of uncertain factors on pollution risk assessment, and thus provides a more reliable basis for groundwater management and decision-making.

RESUMEN

BACKGROUND: Vonoprazan, the new acid suppressive drug, provides more choices for eradicating H. pylori. Therefore, whether vonoprazan and high dose amoxicillin dual therapy is more effective and safer requires a systematic analysis. MATERIALS AND METHODS: A comprehensive search of the literature from PubMed, Embase, Cochrane Library, Web of Science database, up to May 16, 2024. Trails evaluating H. pylori eradicating rates, adverse events, and compliance of VHA dual therapy compared with other therapies were included. RevMan 5.4 was used for statistical analysis. RESULTS: 11 RCTs and 2 retrospective clinical studies with 4570 samples were included. The VHA dual therapy has superior H. pylori eradicating rates (ITT: 86.0% vs 80.7%, OR=1.36, 95% CI 1.07-1.73, P=0.01; PP: 90.6% vs 85.7%, OR=1.42, 95% CI 1.07-1.88, P=0.02), fewer adverse events(15.4% vs 27.7%, OR=0.49, 95%CI 0.35-0.68, P<0.0001), and similar compliance (94.6% vs 93.2%, OR=1.27, 95% CI 0.98-1.64, P=0.07) in comparison to other guideline therapies. According to subgroup analysis with PP data, VHA is more effective than P-BQT (93.5% vs 89.3%, OR=1.76, 95% CI 1.03-3.00, P=0.04). In addition, the eradicating rates of 10-day and 14-day VHA were 92% (95% CI 0.91-0.94) and 93% (95% CI 0.90-0.97) respectively, with the 7-day VHA 65% (95% CI 0.55-0.75). CONCLUSION: VHA dual therapy, for 10 or 14 days showed superior efficacy and safety comparing with therapies recommended by the guidelines, should be prioritized for adoption.

RESUMEN

BACKGROUND/OBJECTIVES: Chronic alcohol consumption causes oxidative stress in the body, which may accumulate excessively and cause a decline in memory; problem-solving, learning, and exercise abilities; and permanent damage to brain structure and function. Consequently, chronic alcohol consumption can cause alcohol-related diseases. MATERIALS/METHODS: In this study, the protective effects of Phyllostachys edulis (Carrière) J. Houz (PE) against alcohol-induced neuroinflammation and cognitive impairment were evaluated using a mouse model. Alcohol (16%, 5 g/kg/day for 6 weeks) and PE (100, 250, and 500 mg/kg/day for 21 days) were administered intragastrically to mice. RESULTS: PE showed a protective effect against memory deficits and cognitive dysfunction caused by alcohol consumption, confirmed through behavioral tests such as the T-maze, object recognition, and Morris water maze tests. Additionally, PE attenuated oxidative stress by reducing lipid oxidation, nitric oxide, and reactive oxygen species levels in the mice's brains, livers, and kidneys. Improvement of neurotrophic factors and downregulation of apoptosis-related proteins were confirmed in the brains of mice fed low and medium concentrations of PE. Additionally, expression of antioxidant enzyme-related proteins GPx-1 and SOD-1 was enhanced in the liver of PE-treated mice, related to their inhibitory effect on oxidative stress. CONCLUSION: This suggests that PE has both neuroregenerative and antioxidant effects. Collectively, these behavioral and histological results confirmed that PE could improve alcohol-induced cognitive deficits through brain neurotrophic and apoptosis protection and modulation of oxidative stress.

RESUMEN

Objective: To describe the feasibility, safety and efficacy of mobilization of the vertebral artery for C2 pedicle screws in cases with the high-riding vertebral artery (HRVA).. Methods: During the period January 2020 to September 2022, fifteen patients underwent posterior occipitocervical fixation in our department. All patients had unilateral HRVA on at least one side that prohibited the insertion of C2 pedicle screws. There were 2 males and 13 females aged 47 ± 11.9 years (range: 17-64 years). After the correction of the vertical dislocation during the operation, the C2 pedicle screw insertion and occipitocervical fixation and fusion were performed using the vertebral artery mobilization technique. A routine three-dimensional reconstructed CT examination was executed to confirm the trajectory of C2 pedicle screws post-operation, and a CT angiography examination was performed when necessary. Neurological function was assessed using the Japanese Orthopedic Association (JOA) scale. The preoperative and postoperative JOA score and the main radiological measurements, including anterior atlantodental interval (ADI), the distance of odontoid tip above Chamberlain line, and clivus-canal angle (CCA), were collected and compared by paired t-test. Results: All 15 patients had atlas assimilation, among which 12 patients had C2-C3 fusion (Klippel-Feil syndrome). Mobilization of the HRVA was successfully completed, and C2 pedicle screws were then fulfilled after the vertebral artery was protected. There was no injury to the vertebral artery during the operation. Meanwhile, no severe surgical complications such as cerebral infarction or aggravated neurological dysfunction occurred during the perioperative period. Satisfactory C2 pedicle screw placement and reduction were reached in all 15 patients. All the patients achieved bone fusion 6 months after surgery. No looseness and shift of internal fixation or reduction loss was observed during the follow-up period. Compared to the preoperative, the postoperative JOA score and the main radiological measurements were remarkably improved and statistically significant. Conclusions: C2 pedicle screw insertion assisted by mobilization of the vertebral artery is safe and considerably effective, providing a choice for internal fixation in cases with high-riding vertebral arteries.

RESUMEN

The escalating demand for portable near-infrared (NIR) light sources has posed a formidable challenge to the development of NIR phosphors characterized by high efficiency and exceptional thermal stability. Taking inspiration from the chemical unit co-substitution strategy, high-performance tunable (Lu3- xCax)(Ga5- xGex)O12:6%Cr3+ (x = 0-3) phosphors are designed with an emission center from 704 to 780 nm and a broadest full width at half maximum (FWHM) of up to 172 nm by introducing Ca2+ and Ge4+ ions into the garnet structure. In particular, Lu3Ga5O12:6%Cr3+ demonstrates an anti-thermal quenching phenomenon (I423K = 113.1%). Compared to Lu3Ga5O12:6%Cr3+, Lu2CaGa4GeO12:6%Cr3+ exhibits significantly improved FWHM and IQE by 108 nm and 25.5%, respectively, while maintaining good thermal stability (I423K = 80.4%). Finally, Lu2CaGa4GeO12:6%Cr3+ phosphor is combined with a 465 nm blue LED chip to fabricate NIR LED devices, exhibiting a NIR electroluminescence efficiency of 13.31%@100 mA and demonstrating successful applications in nocturnal illumination and biomedical imaging technology. This work offers a fresh perspective on the design of highly efficient NIR garnet phosphors.

RESUMEN

In this study, we aimed to investigate the association between handgrip strength (HGS) and cognitive performance in stage 3-5 chronic kidney disease (CKD) patients aged ≥ 60 years. This cross-sectional study analyzed data from National Health and Nutrition Examination Survey (NHANES) database 2011-2014. Three tests were used to assess the cognitive performance, including consortium to establish a registry for Alzheimer's disease (CERAD), animal fluency test (AFT), and digit symbol substitution test (DSST). The multivariate linear regression analyses adjusting for confounding factors were utilized to evaluate the association of HGS with cognitive performance. A total of 678 older stage 3-5 CKD patients were included in this study. After adjusting for multiple factors, a higher HGS was positively associated with a higher CERAD-delayed recall and DSST score. In addition, our analysis indicated that HGS probably correlated with better performance of immediate learning ability in male, while working memory, sustained attention, and processing speed in female. HGS may be an important indicator for cognitive deficits in stage 3-5 CKD patients, especially for learning ability and executive function. Further research to explore the sex-specific and domain-specific and possible mechanisms are required.

Asunto(s)

RESUMEN

Mesosulfuron-methyl, an inhibitor of acetolactate synthase (ALS), has been extensively used in wheats. However, it can damage wheat (Triticum aestivum) and even lead to crop death. Herbicide safeners selectively shield crops from such damage without compromising weed control. To mitigate the phytotoxicity of mesosulfuron-methyl in crops, several purine derivatives were developed based on active substructure splicing. The synthesized title compounds underwent thorough characterization using infrared spectroscopy, 1H nuclear magnetic resonance (1H NMR), 13C nuclear magnetic resonance (13C NMR), and high-resolution mass spectrometry. We evaluated chlorophyll and glutathione contents as well as various enzyme activities to evaluate the safer activity of these compounds. Compounds III-3 and III-7 exhibited superior activity compared with the safener mefenpyr-diethyl. Molecular structure analysis, along with predictions of absorption, distribution, metabolism, excretion, and toxicity, indicated that compound III-7 shared pharmacokinetic traits with the commercial safener mefenpyr-diethyl. Molecular docking simulations revealed that compound III-7 competitively bound to the ALS active site with mesosulfuron-methyl, elucidating the protective mechanism of the safeners. Overall, this study highlights purine derivatives as potential candidates for novel safener development.

RESUMEN

Chiral hybrid metal halides hold great potential as circularly polarized luminescence light sources. Herein, we have obtained two enantiomeric pairs of one-dimensional hybrid chiral manganese(II) chloride single crystals, R/S-(3-methyl piperidine)MnCl3 (R/S-1) and R/S-(3-hydroxy piperidine)MnCl3 (R/S-2), crystallizing in the non-centrosymmetric space group P212121. In comparison to R/S-1, R/S-2 single crystals not only show red emission with near-unity photoluminescence quantum yield (PLQY) and high resistance to thermal quenching but also exhibit circularly polarized luminescence with an asymmetry factor (glum) of 2.5×10-3, which can be attributed to the enhanced crystal rigidity resulting from the hydrogen bonding networks between R/S-(3-hydroxy piperidine) cations and [MnCl6]4- chains. The circularly polarized luminescence activities originate from the asymmetric [MnCl6]4- luminophores induced by N-H⋅⋅⋅Cl hydrogen bonding with R/S-(3-hydroxy piperidine). Moreover, these samples demonstrate great application potential in circularly polarized light-emitting diodes and X-ray scintillators. This work shows a highly efficient photoluminescent Mn-based halide and offers a strategy for designing multifunctional chiral metal halides.

RESUMEN

Hole-transporting layer-free carbon-based perovskite solar cells (HTL-free C-PSCs) hold great promise for photovoltaic applications due to their low cost and outstanding stability. However, the low power conversion efficiency (PCE) of HTL-free C-PSCs mainly results from grain boundaries (GBs). Here, epitaxial growth is proposed to rationally design a hybrid nanostructure of PbI2 nanosheets/perovskite with the desired photovoltaic properties. A post-treatment technique using tri(2,2,2-trifluoromethyl) phosphate (TFEP) to induce in situ epitaxial growth of PbI2 nanosheets at the GBs of perovskite films realizes high-performance HTL-free C-PSCs. The structure model and high-resolution transmission electron microscope unravel the epitaxial growth mechanism. The epitaxial growth of oriented PbI2 nanosheets generates the PbI2 /perovskite heterojunction, which not only passivates defects but forms type-I band alignment, avoiding carrier loss. Additionally, Fourier-transform infrared spectroscopy, 31 P NMR, and 1 H NMR spectra reveal the passivation effect and hydrogen bonding interaction between TFEP and perovskite. As a result, the VOC is remarkably boosted from 1.04 to 1.10 V, leading to a substantial gain in PCE from 14.97% to 17.78%. In addition, the unencapsulated PSC maintains the initial PCE of 80.1% for 1440 h under air ambient of 40% RH. The work offers a fresh perspective on the rational design of high-performance HTL-free C-PSCs.

RESUMEN

4-Hydroxyphenylpyruvate dioxygenase (EC 1.13.11.27, HPPD) is one of the most widely studied herbicide targets and has gained significant attention. To identify potential effective HPPD inhibitors, a rational multistep virtual screening workflow was built, which included CBP models (based on the receptor-ligand interactions in the crystal complex), Hypogen models with activity prediction ability (according to the derivation of structure-activity relationships from a set of molecules with reported activity values), and a consensus docking procedure (consisting of LibDock, Glide, and CDOCKER). About 1 million molecules containing diketone or ß-keto-enol substructures were filtered by Lipinski's rules, CBP model, and Hypogen model. A total of 12 compounds with similar docking postures were generated by consensus docking. Eventually, four molecules were screened based on the specific binding pattern and affinity of the HPPD inhibitor. The biological evaluation in vivo displayed that compounds III-1 and III-2 exhibited comparable herbicidal activity to isoxaflutole and possessed superior safety on various crops (wheat, rice, sorghum, and maize). The ADMET prediction (absorption, distribution, metabolism, excretion, and toxicity) showed that compound III possessed relatively good toxicological results. This work provides a theoretical basis and valuable reference for the virtual screening and molecular design of novel HPPD inhibition herbicides.

Asunto(s)

RESUMEN

OBJECTIVE: Dynamic changes in ischemic pathology after stroke suggested a "critical window" of enhanced neuroplasticity immediately after stroke onset. Although physical exercise has long been considered a promising strategy of stroke rehabilitation, very early physical exercise may exacerbate brain injury. Since remote ischemic conditioning (RIC) promotes neuroprotection and neuroplasticity, the present study combined RIC with sequential exercise to establish a new rehabilitation strategy for a better rehabilitative outcome. METHODS: A total of 120 adult male Sprague-Dawley rats were used and divided into five groups: (1) sham, (2) stroke, (3) stroke with exercise, (4) stroke with RIC, and (5) stroke with RIC followed by exercise. Brain damage was evaluated by infarct volume, neurological deficit, cell death, and lactate dehydrogenase (LDH) activity. Long-term functional outcomes were determined by grid walk tests, rotarod tests, beam balance tests, forelimb placing tests, and the Morris water maze. Neuroplasticity was evaluated through measurements of both mRNA and protein levels of synaptogenesis (synaptophysin [SYN], post-synaptic density protein-95 [PSD-95], and brain-derived neurotrophic factor [BDNF]) and angiogenesis (vascular endothelial growth factor [VEGF], angiopoietin-1 [Ang-1], and angiopoietin-2 [Ang-2]). Inflammasome activation was measured by concentrations of interleukin-18 (IL-18) and IL-1ß detected by enzyme-linked immunosorbent assay (ELISA) kits, mRNA expressions of NLR pyrin domain containing 3 (NLRP3), apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), IL-18 and IL-1ß, and protein quantities of NLRP3, ASC, cleaved-caspase-1, gasdermin D-N (GSDMD-N), and IL-18 and IL-1ß. Stress granules (SGs), including GTPase-activating protein-binding protein 1 (G3BP1), T cell-restricted intracellular antigen-1 (TIA1), and DEAD-box RNA helicase 3X (DDX3X) were evaluated at mRNA and protein levels. The interactions between DDX3X with NLRP3 or G3BP1 were determined by immunofluorescence and co-immunoprecipitation. RESULTS: Early RIC decreased infarct volumes, neurological deficits, cell death, and LDH activity at post-stroke Day 3 (p < 0.05). All treatment groups showed significant improvement in functional outcomes, including sensory, motor, and cognitive functions. RIC and exercise, as compared to RIC or physical exercise alone, had improved functional outcomes after stroke (p < 0.05), as well as synaptogenesis and angiogenesis (p < 0.05). RIC significantly reduced mRNA and protein expressions of NLRP3 (p < 0.05). SGs formation peaked at 0 h after ischemia, then progressively decreased until 24 h postreperfusion, which was reversed by RIC (p < 0.05). The assembly of SGs consumed DDX3X and then inhibited NLRP3 inflammasome activation. CONCLUSIONS: RIC followed by exercise induced a better rehabilitation in ischemic rats, while early RIC alleviated ischemia-reperfusion injury via stress-granule-mediated inhibition of NLRP3 inflammasome.

Asunto(s)

RESUMEN

Recent studies using cell type-specific knockout mouse models have improved our understanding of the pathophysiological relevance of suppressor of lin-12-like-HMG-CoA reductase degradation 1 (SEL1L-HRD1) endoplasmic reticulum-associated (ER-associated) degradation (ERAD); however, its importance in humans remains unclear, as no disease variant has been identified. Here, we report the identification of 3 biallelic missense variants of SEL1L and HRD1 (or SYVN1) in 6 children from 3 independent families presenting with developmental delay, intellectual disability, microcephaly, facial dysmorphisms, hypotonia, and/or ataxia. These SEL1L (p.Gly585Asp, p.Met528Arg) and HRD1 (p.Pro398Leu) variants were hypomorphic and impaired ERAD function at distinct steps of ERAD, including substrate recruitment (SEL1L p.Gly585Asp), SEL1L-HRD1 complex formation (SEL1L p.Met528Arg), and HRD1 activity (HRD1 p.Pro398Leu). Our study not only provides insights into the structure-function relationship of SEL1L-HRD1 ERAD, but also establishes the importance of SEL1L-HRD1 ERAD in humans.

Asunto(s)

RESUMEN

The low power conversion efficiency (PCE) of hole transport materials (HTM) - free carbon-based perovskite solar cells (C-PSCs) poses a challenge. Here, a novel 2D Eu-TCPP MOF (TCPP; [tetrakis (4-carboxyphenyl) porphyrin]) sandwiched between the perovskite layer and the carbon electrode is used to realize an effective and stable HTM-free C-PSCs. Relying on the synergistic effect of both the metal-free TCPP ligand with a unique absorption spectrum and hydrophobicity and the EuO4(OH)2 chain in the Eu-TCPP MOF, defects are remarkably suppressed and light-harvesting capability is significantly boosted. Energy band alignment is achieved after Eu-TCPP MOF treatment, promoting hole collection. Förster resonance energy transfer results in improved light utilization and protects the perovskite from decomposition. As a result, the HTM-free C-PSCs with Eu-TCPP MOF reach a champion PCE of 18.13%. In addition, the unencapsulated device demonstrates outstanding thermal stability and UV resistance and keeps 80.6% of its initial PCE after 5500 h in a high-humidity environment (65%-85% RH).

RESUMEN

Glioma, the most common primary malignant tumor of the central nervous system, lacks effective targeted therapies. This study investigates the role of SOAT1, a key gene involved in cholesterol esterification, in glioma prognosis and its association with ferroptosis. Although the impact of SOAT1 on glioma prognosis has been recognized, its precise mechanism remains unclear. In this study, we demonstrate that inhibiting SOAT1 increases the sensitivity of glioma cells to ferroptosis, both in vitro and in vivo. Mechanistically, SOAT1 positively modulates the expression of SLC40A1, an iron transporter, resulting in enhanced intracellular iron outflow, reduced intracellular iron levels, and subsequent disruption of ferroptosis. Importantly, we find that SOAT1 regulates ferroptosis independently of SREBPs, which are known to be involved in ferroptosis regulation. Furthermore, we identify the involvement of the PI3K-AKT-mTOR signaling pathway in mediating the regulatory effects of SOAT1 on SLC40A1 expression and ferroptosis sensitivity. These findings highlight the contribution of intracellular signaling cascades in the modulation of ferroptosis by SOAT1. We show that inhibiting SOAT1 enhances the efficacy of radiotherapy in gliomas, both in vitro and in vivo, by promoting sensitivity to ferroptosis. This suggests that targeting SOAT1 could potentially improve therapeutic outcomes for glioma patients. In summary, this study uncovers the pivotal role of SOAT1 as a link between cholesterol esterification and ferroptosis in glioma. Our findings underscore the potential of SOAT1 as a promising clinical therapeutic target, providing new avenues for the development of effective treatments for glioma. Further research is warranted to unravel the complete regulatory mechanisms of SOAT1 and explore its clinical applications.

Asunto(s)

RESUMEN

Although endovascular therapy demonstrates robust clinical efficacy in acute ischemic stroke (AIS), not all stroke patients benefit from successful reperfusion. This study aimed to evaluate the safety, feasibility, and preliminary efficacy of intra-arterial administration of glyceryl trinitrate (GTN) after endovascular recanalization for neuroprotection. This is a prospective randomized controlled study. Eligible patients were randomized to receive 800 µg GTN or the same volume of normal saline through the catheter after recanalization. The primary outcome was symptomatic intracranial hemorrhage (ICH), while secondary outcomes included mortality, functional outcome, infarction volume, complications, and blood nitrate index (NOx). A total of 40 patients were enrolled and randomized with no participants being lost to follow-up. There was no significant difference in the proportion of sICH between GTN and control groups. Additionally, no significant difference was observed in mortality or rates of neurological deterioration and other complications. Favorable trends, while non-significant, were noted in both outcome and imaging for functional independence at 90 days and reduction in final infarct volume (75.0% vs 65.0%; 33.2 vs 38.9 ml) for the GTN group. Moreover, the concentration of blood NOx in the GTN group was significantly higher than in the control group at 2 h after GTN administration (26.2 vs 18.0 µmol/l, p < 0.05). The AGAIN study suggests intra-arterial administration of GTN post-endovascular therapy is safe and feasible and GTN successfully raised NOx levels over controls at 2 h. A multi-center randomized controlled trial with a larger sample size is warranted to determine GTN neoadjuvant efficacy.

Asunto(s)

RESUMEN

INTRODUCTION: Protein-energy waste (PEW) is a common complication in patients with chronic kidney disease (CKD), among which skeletal muscle atrophy is one of the most important clinical features of PEW. Pyroptosis is a type of proinflammatory, programmed cell death associated with skeletal muscle disease. Irisin, as a novel myokine, has attracted extensive attention for its protective role in the complications associated with CKD, but its role in muscle atrophy in CKD is unclear. METHODS: Palmitic acid (PA)-induced muscular atrophy was evaluated by a reduction in C2C12 myotube diameter. Muscle atrophy model was established in male C57BL/6J mice treated with 0.2% adenine for 4 weeks and then fed a 45% high-fat diet. Blood urea nitrogen and creatinine levels, body and muscle weight, and muscle histology were assessed. The expression of carnitine palmitoyltransferase 1A (CPT1A) and pyroptosis-related protein was analysed by Western blots or immunohistochemistry. The release of IL-1ß was detected by enzyme-linked immunosorbent assay. RESULTS: In this study, we showed that PA-induced muscular atrophy manifested as a reduction in C2C12 myotube diameter. During this process, PA can also induce pyroptosis, as shown by the upregulation of NLRP3, cleaved caspase-1 and GSDMD-N expression and the increased IL-1ß release and PI-positive cell rate. Inhibition of caspase-1 or NLRP3 attenuated PA-induced pyroptosis and myotube atrophy in C2C12 cells. Importantly, irisin treatment significantly ameliorated PA-induced skeletal muscle pyroptosis and atrophy. In terms of mechanism, PA upregulated CPT1A, a key enzyme of fatty acid oxidation (FAO), and irisin attenuated this effect, which was consistent with etomoxir (CPT1A inhibitor) treatment. Moreover, irisin improved skeletal muscle atrophy and pyroptosis in adenine-induced mice by regulating FAO. CONCLUSION: Our study firstly verifies that pyroptosis is a novel mechanism of skeletal muscle atrophy in CKD. Irisin ameliorates skeletal muscle atrophy by inhibiting FAO and pyroptosis in CKD, and irisin may be developed as a potential therapeutic agent for the treatment of muscle wasting in CKD patients.

Asunto(s)

RESUMEN

This study aims to investigate the protective effects and mechanisms of pectolinarin against oxidative stress-induced cell damage in SH-SY5Y cells. Neurodegenerative diseases-such as Alzheimer's disease-are potentially associated with oxidative stress, which causes excessive production of reactive oxygen species (ROS) that damage DNA and proteins in neuronal cells. The results of this study demonstrate that pectolinarin can scavenge hydroxyl and nitric oxide radicals in a concentration-dependent manner. Moreover, pectolinarin significantly increased cell viability while reducing ROS production and LDH release in the hydrogen peroxide (H2O2)-induced control group. Additionally, Pectolinarin recovered protein expression from H2O2-altered levels back to close-to-normal SH-SY5Y cell levels for components of the oxidative stress, inflammation, and apoptosis pathways-such as nuclear factor erythroid 2-related factor 2 (Nrf2), kelch-like ECH-associated protein (Keap1), anti-heme oxygenase 1 (HO-1), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-1ß (IL-1ß), B-cell lympho-ma-2 (Bcl-2) protein, and Bcl-2-associated X protein (Bax). These findings suggest that pectolinarin has the potential to be used as a plant material for functional foods to be applied in the treatment of neurodegenerative diseases, such as Alzheimer's disease, by mitigating oxidative stress-induced damage to neuronal cells.

Asunto(s)

RESUMEN

BACKGROUND: The function of macula densa nitric oxide synthase 1 (NOS1) in the regulation of renin release is controversial. This study was conducted to further elucidate the role of macula densa NOS1 in renin release and blood pressure regulation in response to salt challenges and hemorrhagic shock. METHODS: To investigate the specific role of NOS1 in the macula densa within the kidney in response to varying sodium concentrations in the diet, tissue macula densa-specific NOS1 knockout (MD-NOS1KO) and wild type (WT) mice were subjected to sequential low (0.1% NaCl) and high (1.4% NaCl) sodium diets. Separate groups of mice, consisting of both MD-NOS1KO subgroup and WT subgroup, were induced hemorrhagic shock by retro-orbital bleeding of 12 mL blood/kg body weight. Mean arterial pressure (MAP) was measured by a radio-telemetry system. Plasma renin concentration (PRC) was measured with the radioimmunoassay for both sodium diet and hemorrhagic shock experiments. RESULTS: PRCs were 371 ± 95 and 411 ± 68 ng/mL/hr in WT and MD-NOS1KO mice fed a normal sodium diet, respectively. Low salt intake stimulated an increase in the renin release by about 260% in WT mice (PRC = 1364 ± 217 ng/mL/hr, p < 0.0001) compared to the PRC under normal salt diet. However, the stimulation was significantly blunted in MD-NOS1KO mice (PRC = 678 ± 104 ng/mL/hr, p < 0.001). High salt intake suppressed the PRC to about 61% of the PRC level under a normal salt diet (p < 0.0001). Deletion of macula densa NOS1 further inhibited renin release to 33% of the levels of a normal salt diet. Hemorrhagic shock induced about a 3-fold increase in PRC in WT mice, but only about a 54% increase in the MD-NOS1KO mice (p < 0.0001). The MAP values were substantially greater in WT mice than in MD-NOS1KO mice within the first 6 hours following hemorrhagic shock (p < 0.001). Thus, WT mice showed a much quicker recovery in MAP than MD-NOS1KO mice. CONCLUSIONS: Our study demonstrated that macula densa NOS1 plays an important role in mediating renin release. This mechanism is essential in maintaining blood pressure under hypovolemic situations such as hemorrhagic shock.

Asunto(s)

RESUMEN

Fe3+-doped near-infrared (NIR) phosphors have received a lot of interest because they are nontoxic, inexpensive, and ecologically benign. In this work, Fe3+-activated Li2ZnAO4 (A = Si, Ge) phosphors were synthesized by solid-phase reactions, in which Fe3+ entered the Zn2+ tetrahedral site. When excited by 300 nm UV light, broad NIR emission bands at 750 nm (Li2ZnSiO4: Fe3+) and 777 nm (Li2ZnGeO4: Fe3+) were observed, with internal quantum efficiencies (IQE) of 62.70% (Li2ZnSiO4: Fe3+) and 30.57% (Li2ZnGeO4: Fe3+). The thermal stability was increased from 35.43 to 49.79% at 373 K via cationic regulation. The combination of activation energy, electron-phonon coupling, and Debye temperature explained the improved thermal stability of Li2ZnGeO4: Fe3+ phosphor. Besides, the as-synthesized phosphor demonstrated sensitive and selective Cu2+ ion detection.