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1.
Front Plant Sci ; 15: 1392355, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38721334

RESUMEN

Selenium (Se) is a crucial micronutrient for human health. Plants are the primary source of Se for humans. Selenium in the soil serves as the primary source of Se for plants. The soil contains high total Se content in large areas in Guangxi, China. However, the available Se is low, hindering Se uptake by plants. Microorganisms play a pivotal role in the activation of Se in the soil, thereby enhancing its uptake by plants. In this study, selenobacteria were isolated from Se-rich soils in Guangxi. Then two selenobacteria strains, YLB1-6 and YLB2-1, representing the highest (30,000 µg/mL) and lowest (10,000 µg/mL) Se tolerance levels among the Se-tolerant bacteria, were selected for subsequent analysis. Although the two selenobacteria exhibited distinct effects, they can significantly transform Se species, resulting in a decrease in the soil residual Se (RES-Se) content while concurrently increasing the available Se (AVA-Se) content. Selenobacteria also enhance the transformation of Se valencies, with a significant increase observed in soluble Se6+ (SOL-Se6+). Additionally, selenobacteria can elevate the pH of acidic soil. Selenobacteria also promote the uptake of Se into plants. After treatment with YLB1-6 and YLB2-1, the Se content in the aboveground part of Chinese flowering cabbage increased by 1.96 times and 1.77 times, respectively, while the Se accumulation in the aboveground part of the plant significantly increased by 104.36% and 81.69%, respectively, compared to the control. Further whole-genome sequencing revealed the genetic difference between the two selenobacteria. Additionally, 46 and 38 candidate genes related to selenium utilization were identified from YLB1-6 and YLB2-1, respectively. This work accelerates our understanding of the potential molecular mechanism of Se biofortification by selenobacteria. It also provides microorganisms and gene targets for improving crop varieties or microorganisms to exploit the rich Se source in soil.

2.
Heliyon ; 10(8): e29447, 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38644824

RESUMEN

Objective: Grifolin is a natural secondary metabolite isolated from edible fruiting bodies of the mushroom Albatrellus confluens. Grifolin has antitumor activities in several types of cancer. We aimed to determine the effects of grifolin on lung cancer. Methods: We determined the proliferation, migration, invasion, and apoptosis of lung cancer cells using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, Ethynyl deoxyuridine, colony formation, wound scratch, transwell, flow cytometry, and xenograft mouse assays. Molecular docking evaluated the binding relation between grifolin and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA). The levels of PIK3CA, AKT, and p-AKT were measured by western blot. Results: Grifolin (10, 20, or 40 µM) inhibited the proliferation, migration, and invasion of lung cancer cells, and induced cell cycle arrest and apoptosis. Grifolin also decreased CDK4, CDK6, and CyclinD1 expression and significantly decreased PIK3CA and p-AKT expression in lung cancer cells. These anticancer effects were abolished by 740Y-P. Conclusions: Grifolin regulates the PI3K/AKT pathway, thus inhibiting lung cancer progression.

3.
Int Immunopharmacol ; 130: 111735, 2024 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-38412675

RESUMEN

OBJECTIVE: To identify the long non-coding RNA (lncRNA) expression profiling in exosomes derived from synovial fluid of rheumatoid arthritis (RA) patients, and carry out bioinformatics analysis on target genes of differentially expressed lncRNAs. METHODS: Exosomes were isolated from synovial fluid via ultracentrifugation. RNAs were extracted from exosomes by using HiPure Liquid RNA/miRNA kits, followed by lncRNA sequencing. Differentially expressed lncRNAs in RA were screened, and bioinformatics analysis of their target genes was carried out. qRT-PCR was used to verify the lncRNA expression levels. RESULTS: Compared with osteoarthritis (OA), 347 lncRNAs were found differentially expressed in RA. Compared with gout, 805 lncRNAs were found differentially expressed in RA. Compared with both OA and gout, 85 lncRNAs were found specially expressed in RA (65 were upregulated (including ENST00000433825.1)). Functional analysis of target genes of the specially expressed lncRNAs revealed significant enrichment of "autophagy" and "mTOR signaling pathway". The qRT-PCR results indicated that ENST00000433825.1 was highly expressed in RA, compared with both OA and gout (P < 0.05), which matched the lncRNA sequencing results. Correlation analysis showed that the level of ENST00000433825.1 in RA patients was significantly and positively correlated with the level of C-reactive protein (CRP) (P < 0.001). CONCLUSIONS: The lncRNA expression profiling in exosomes derived from synovial fluid of RA was significantly different from OA and gout. ENST00000433825.1 was highly and uniquely expressed in RA and significantly and positively correlated with CRP, which might provide a diagnostic and therapeutic biomarker for RA.


Asunto(s)
Artritis Reumatoide , Exosomas , Gota , Osteoartritis , ARN Largo no Codificante , Humanos , ARN Largo no Codificante/genética , Líquido Sinovial/metabolismo , Exosomas/genética , Exosomas/metabolismo , Artritis Reumatoide/genética , Artritis Reumatoide/metabolismo , Osteoartritis/genética , Osteoartritis/metabolismo
4.
Nurs Crit Care ; 2024 Feb 15.
Artículo en Inglés | MEDLINE | ID: mdl-38358027

RESUMEN

BACKGROUND: Although the circuit condensate, an ideal bacterial reservoir during mechanical ventilation, may flow into the humidifier reservoir, no studies have investigated if humidifier reservoir colonized bacteria colonize other circuit locations with airflow. AIMS: We aimed to prove whether the humidifier reservoir colonized bacteria colonize other circuit locations with airflow and provide some advice on the disposal of condensate in the clinical setting. STUDY DESIGN: An in vitro experiment was conducted. Mechanical ventilation simulators (n = 90) were divided into sterile water group (n = 30) and broth group (n = 60). In the sterile water group, sterile water was used for humidification, either Acinetobacter baumannii or Pseudomonas aeruginosa were inoculated to humidifier water in the humidifier reservoir, each accounted for 50% of the simulators. The broth group was performed the same as the sterile water group except for the addition of broth into the humidified water. After 24, 72, and 168 h of continuous ventilation, the humidifier water and different locations of the circuits were sampled for bacterial culture. RESULTS: All bacterial culture results of the sterile water group were negative. Bacteria in the humidifier water continued to proliferate in the broth group. With prolonged ventilation, the bacteria at the humidifier reservoir outlet increased. The bacteria at the humidifier reservoir outlet were much more in the Pseudomonas aeruginosa subgroup than in the Acinetobacter baumannii subgroup and the difference was statistically significant (p < .05). During continuous ventilation, no bacterial growth occurred at 10 cm from the humidifier reservoir outlet and the Y-piece of the ventilator circuits. CONCLUSIONS: Sterile water in the humidifier reservoir was not conducive to bacterial growth. Even if bacteria grew in the humidifier reservoir and could reach the humidifier reservoir outlet, colonization of further circuit locations with the airflow was unlikely. During a certain mechanical ventilation time, the amount of bacteria reaching the outlet of the humidifier reservoir varied due to different mobility of bacteria. RELEVANCE TO CLINICAL PRACTICE: In a clinical setting, nurses should not worry about a small amount of condensate backflow into the humidifier reservoir. Draining condensate into the humidifier reservoir can be used as a low risk and convenient method in clinical practice.

5.
Exp Ther Med ; 27(2): 73, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38264429

RESUMEN

Hydrochlorothiazide (HCTZ) is a commonly used diuretic antihypertensive drug that can cause electrolyte disorders, hyperglycemia and hyperuricemia as well as rare life-threatening adverse drug reactions. These include non-cardiogenic pulmonary edema, interstitial pneumonia, angioedema and aplastic anemia. The present report describes a case of a 59-year-old man who developed a hypersensitivity reaction to HCTZ. Specifically, the patient presented with symptoms of cough, chest tightness and shortness of breath, with pneumonic consolidation on chest CT and elevated levels of white blood cell count, neutrophil percentage, C-reactive protein and procalcitonin. A presumptive diagnosis of severe pneumonia was made initially. However, during the gradual recovery of the patient through treatment, he mistakenly ingested HCTZ containing losartan potassium intended for another patient, which resulted in symptoms similar to those observed upon admission. Upon further inquiry into the medical history, it was revealed that the patient had also taken irbesartan/HCTZ 4 h prior to hospitalization. There was no evidence of a pathogenic infection. Therefore, HCTZ-induced anaphylactic reaction was considered to be the most likely etiology for his severe shock. Treatments including epinephrine, methylprednisolone and respiratory support were administered. After 7 days, the patient was transferred from the Respiratory Intensive Care Unit [The Affiliated Jiangning Hospital of Nanjing Medical University (Nanjing, China)] to a general ward. During the follow-up, 12 months after advising the patient to discontinue HCTZ, there had been no recurrence of the aforementioned symptoms. At the time of publication, the patient is currently alive.

6.
Environ Sci Pollut Res Int ; 31(6): 9106-9120, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38182955

RESUMEN

Zhejiang Province is one of the top five major provinces producing traditional Chinese medicines (TCMs) and is famous for Zhebawei (in Chinese), the eight popular geo-authentic TCMs including Rhizoma Atractylodis Macrocephalae, Radix Paeoniae Alba, Thunberg Fritillary Bulb, Chrysanthemum morifolium, Corydalis yanhusuo W. T. Wang, Scrophulariae Radix, Ophiopogonis Radix, and Curcuma Wenyujin Y. H. Chen et C. Ling. High proportion application and residue of pesticides directly affect the quality and yield of TCMs. In this study, pesticides residual levels in crude and processing samples were assessed along with their health risks in Zhebawei primarily produced in Zhejiang Province. In total, the exceeded ratios of pesticides residual concentrations in above mentioned eight species were 15/23, 4/7, 26/70, 22/44, 10/19, 8/12, 7/15, and 0/2, respectively. No acute dietary intake health risks were found but the long-term risks from permethrin in S. Radix should be carefully considered, with all quotient values being higher than 2.1 for all groups between 7 and 70 years. Furthermore, the risks of total benzene hexachloride in T. Fritillary Bulb and carbendazim in C. morifolium should be closely monitored. Suggestions for the cultivation and pesticide management of herbal medicines have been proposed to promote the quality of medicinal materials.


Asunto(s)
Medicamentos Herbarios Chinos , Plaguicidas , Plaguicidas/análisis , Medicamentos Herbarios Chinos/química , Medicina Tradicional China , Rizoma/química , Raíces de Plantas
7.
Cell Cycle ; 22(17): 1827-1853, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37522842

RESUMEN

Background: Desipramine a representative of tricyclic antidepressants (TCAs) promotes recovery of depressed patients by inhibition of reuptake of neurotransmitters serotonin (SER) and norepinephrine (NE) in the presynaptic membrane by directly blocking their respective transporters SERT and NET.Aims: To study the effect of desipramine on programmed erythrocyte death (eryptosis) and explore the underlying mechanisms.Methods: Phosphatidylserine (PS) exposure on the cell surface as marker of cell death was estimated from annexin-V-binding, cell volume from forward scatter in flow cytometry. Hemolysis was determined photometrically, and intracellular glutathione [GSH]i from high performance liquid chromatography.Results: Desipramine dose-dependently significantly enhanced the percentage of annexin-V-binding cells and didn´t impact glutathione (GSH) synthesis. Desipramine-induced eryptosis was significantly reversed by pre-treatment of erythrocytes with either nitric oxide (NO) donor sodium nitroprusside (SNP) or N-acetyl-L-cysteine (NAC). The highest inhibitory effect was obtained by using both inhibitors together. Calcium (Ca2+) depletion aggravated desipramine-induced eryptosis. Changing the order of treatment, i.e. desipramine first followed by inhibitors, could not influence the inhibitory effect of SNP or NAC.Conclusion: Antidepressants-caused intoxication can be treated by SNP and NAC, respectively. B) Patients with chronic hypocalcemia should not be treated with tricyclic anti-depressants or their dose should be noticeably reduced.


Asunto(s)
Eriptosis , Donantes de Óxido Nítrico , Humanos , Donantes de Óxido Nítrico/farmacología , Donantes de Óxido Nítrico/metabolismo , Nitroprusiato/farmacología , Nitroprusiato/metabolismo , Calcio/metabolismo , Acetilcisteína/farmacología , Desipramina/farmacología , Desipramina/metabolismo , Eritrocitos/metabolismo , Glutatión/metabolismo , Glutatión/farmacología , Anexinas/metabolismo , Anexinas/farmacología , Fosfatidilserinas/metabolismo , Tamaño de la Célula , Ceramidas/metabolismo , Especies Reactivas de Oxígeno/metabolismo , Estrés Oxidativo
8.
Toxics ; 11(7)2023 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-37505559

RESUMEN

Per- and polyfluoroalkyl substances (PFASs) are a class of compounds that persist in the environment globally. Besides being transported to the soil and sediments, which act as their sinks, PFASs can be transferred to several species of higher organisms directly or via bacteria, eliciting a wide range of adverse effects. Caenorhabditis elegans has been widely used in toxicological studies and life science research owing to its numerous advantages over traditional vertebrate models; notably, C. elegans has 65% conserved human-disease-associated genes and does not require ethical approvals for experimental use. This review covers a range of topics, from reported accumulation characteristics and lethal concentrations of PFAS in C. elegans to the mechanisms underlying the toxicity of PFAS at different levels, including reproductive, developmental, cellular, neurologic, oxidative, metabolic, immune, and endocrine toxicities. Additionally, the toxicity levels of some PFAS substitutes are summarized. Lastly, we discuss the toxicological mechanisms of these PFAS substitutes and the importance and promising potential of nematodes as in vivo models for life science research, epidemiological studies (obesity, aging, and Alzheimer's disease research), and toxicological investigations of PFASs and other emerging pollutants compared with other soil animals or model organisms.

9.
Acta Pharmacol Sin ; 44(3): 546-560, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36042291

RESUMEN

Sirtuin3 (SIRT3), a class III histone deacetylase, is implicated in various cardiovascular diseases as a novel therapeutic target. SIRT3 has been proven to be cardioprotective in a model of Ang II-induced cardiac hypertrophy. However, a few small-molecule compounds targeting deacetylases could activate SIRT3. In this study, we generated a novel SIRT3 activator, 3-(2-bromo-4-hydroxyphenyl)-7-hydroxy-2H-chromen-2-one (SZC-6), through structural optimization of the first SIRT3 agonist C12. We demonstrated that SZC-6 directly bound to SIRT3 with Kd value of 15 µM, and increased SIRT3 deacetylation activity with EC50 value of 23.2 ± 3.3 µM. In neonatal rat cardiomyocytes (NRCMs), pretreatment with SZC-6 (10, 20, 40 µM) dose-dependently attenuated isoproterenol (ISO)-induced hypertrophic responses. Administration of SZC-6 (20, 40 and 60 mg·kg-1·d-1, s.c.) for 2 weeks starting from one week prior ISO treatment dose-dependently reversed ISO-induced impairment of diastolic and systolic cardiac function in wild-type mice, but not in SIRT3 knockdown mice. We showed that SZC-6 (10, 20, 40 µM) dose-dependently inhibited cardiac fibroblast proliferation and differentiation into myofibroblasts, which was abolished in SIRT3-knockdown mice. We further revealed that activation of SIRT3 by SZC-6 increased ATP production and rate of mitochondrial oxygen consumption, and reduced ROS, improving mitochondrial function in ISO-treated NRCMs. We also found that SZC-6 dose-dependently enhanced LKB1 phosphorylation, thereby promoting AMPK activation to inhibit Drp1-dependent mitochondrial fragmentation. Taken together, these results demonstrate that SZC-6 is a novel SIRT3 agonist with potential value in the treatment of cardiac hypertrophy partly through activation of the LKB1-AMPK pathway.


Asunto(s)
Sirtuina 3 , Ratones , Ratas , Animales , Sirtuina 3/metabolismo , Proteínas Quinasas Activadas por AMP/metabolismo , Cardiomegalia/inducido químicamente , Miocitos Cardíacos/metabolismo , Isoproterenol
10.
RSC Adv ; 12(54): 34843-34850, 2022 Dec 06.
Artículo en Inglés | MEDLINE | ID: mdl-36540208

RESUMEN

Three novel pharmaceutical salts of cephalexin (CPX) with 2,6-dihydroxybenzoic acid (DHBA), 5-chlorosalicylic acid (CSA) and 5-sulfosalicylic acid (SSA), which were obtained and thoroughly explored by various analytical techniques, were found to be crystallized invariably in hydrated forms. It is the proton transfer from carboxylic or sulfonic counterions to the CPX molecules that results in the salt formation. Crystal structure analyses reveal that the N-H⋯O and O-H⋯O hydrogen bonding interactions among the CPX, acidic guest molecules and water molecules play a crucial role in the packing motifs of crystal stabilization. All the salts exhibit higher solubility compared with the parent drug. These salts offer an alternative way of increasing the number of solid forms for CPX, which facilitates selection of a suitable form in the context of drug formulation development for further repurposing investigations.

11.
ACS Appl Mater Interfaces ; 14(32): 36411-36424, 2022 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-35917371

RESUMEN

Despite recent preclinical progress with oncolytic bacteria in cancer therapy, dose-limiting toxicity has been a long-standing challenge for clinical application. Genetic and chemical modifications for enhancing the bacterial tumor-targeting ability have been unable to establish a balance between increasing its specificity and effectiveness while decreasing side effects. Herein, we report a simple, highly efficient method for rapidly self-assembling a clinically used lipid on bacterium and for reducing its minimum effective dose and toxicity to normal organs. The resultant bacteria present the ability to reverse-charge between neutral and acidic solutions, thus enabling weak interactions with the negatively charged normal cells, hence increasing their biocompatibility with blood cells and with the immune system. Additionally, the lipid-coated bacteria exhibit a longer blood circulation lifetime and low tissue trapping compared with the wild-type strains. Thereby, the engineered bacteria show enhanced tumor specificity and effectiveness even at low doses. Multiple visualization techniques are used for vividly demonstrating the time course of bacterial circulation in the blood and normal organs after intravenous administration. We believe that these methods for biointerfacial lipid self-assembly and evaluation of bacterial systemic circulation possess vast potential in exquisitely fabricating engineered bacteria for cancer therapy in the future.


Asunto(s)
Neoplasias , Bacterias , Humanos , Lípidos , Neoplasias/tratamiento farmacológico , Electricidad Estática
13.
Environ Monit Assess ; 194(5): 343, 2022 Apr 07.
Artículo en Inglés | MEDLINE | ID: mdl-35389100

RESUMEN

In this study, we propose and construct a novel model that measures regional green development level based on the "three-circle" conceptual framework for green development. Using Jiangsu Province in eastern China as a case study, the spatial-temporal characteristics and dynamics of the green development level from 2000 to 2020 were evaluated using a multi-source dataset at the grid-cell level. Our results show that (1) the analytical hierarchy process-based model proposed herein has higher reliability in terms of the development level measurement than principal component analysis and the entropy weight method. In addition, the average score of green development in the study area was approximately 0.53. Spatially, the green development level in the eastern coastal areas of the study area was found to be generally higher than in other regions, while that in southwestern regions is relatively low. In terms of sub-regions, the green development level scores of the study area have been ranked as follows: middle Jiangsu > southern Jiangsu > northern Jiangsu. (2) It was observed that the gravity center of the green development level can be divided into three stages during the study, with a whole had shifted to the north. (3) For most cities in Jiangsu, the green development level initially increased at first, then declined, and then increased again. (4) In the future, the green development level of Jiangsu Province should pay more attention to promoting regional coordinated development and relationships between society and the environment under rapid economic development.


Asunto(s)
Monitoreo del Ambiente , Desarrollo Sostenible , China , Ciudades , Desarrollo Económico , Reproducibilidad de los Resultados
14.
Kidney Blood Press Res ; 47(6): 399-409, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35339998

RESUMEN

BACKGROUND/AIMS: Vasopressin is a powerful stimulator of vascular calcification, augmenting osteogenic signaling in vascular smooth muscle cells (VSMCs) including upregulation of transcription factors such as core-binding factor α-1 (CBFA1), msh homeobox 2 (MSX2), and SRY-Box 9 (SOX9), as well as of tissue-nonspecific alkaline phosphatase (ALPL). Vasopressin-induced osteogenic signaling and calcification require the serum- and glucocorticoid-inducible kinase 1 (SGK1). Known effects of SGK1 include upregulation of Na+/H+ exchanger 1 (NHE1). NHE1 further participates in the regulation of reactive oxygen species (ROS). NHE1 has been shown to participate in the orchestration of bone mineralization. The present study, thus, explored whether vasopressin modifies NHE1 expression and ROS generation, as well as whether pharmacological inhibition of NHE1 disrupts vasopressin-induced osteogenic signaling and calcification in VSMCs. METHODS: Human aortic smooth muscle cells (HAoSMCs) were treated with vasopressin in the absence or presence of SGK1 silencing, SGK1 inhibitor GSK-650394, and NHE1 blocker cariporide. Transcript levels were determined by using quantitative real-time polymerase chain reaction, protein abundance by Western blotting, ROS generation with 2',7'-dichlorofluorescein diacetate fluorescence, and ALP activity and calcium content by using colorimetric assays. RESULTS: Vasopressin significantly enhanced the NHE1 transcript and protein levels in HAoSMCs, effects significantly blunted by SGK1 inhibition with GSK-650394 or SGK1 silencing. Vasopressin increased ROS accumulation, an effect significantly blocked by the NHE1 inhibitor cariporide. Vasopressin further significantly increased osteogenic markers CBFA1, MSX2, SOX9, and ALPL transcript levels, as well as ALP activity and calcium content in HAoSMCs, all effects significantly blunted by SGK1 silencing or in the presence of GSK-650394 or cariporide. CONCLUSION: Vasopressin stimulates NHE1 expression and ROS generation, an effect dependent on SGK1 and required for vasopressin-induced stimulation of osteogenic signaling and calcification of VSMCs.


Asunto(s)
Calcificación Fisiológica , Calcificación Vascular , Calcio/metabolismo , Células Cultivadas , Humanos , Miocitos del Músculo Liso , Especies Reactivas de Oxígeno/metabolismo , Intercambiador 1 de Sodio-Hidrógeno , Calcificación Vascular/metabolismo , Vasopresinas/metabolismo
15.
Hum Cell ; 35(3): 871-884, 2022 May.
Artículo en Inglés | MEDLINE | ID: mdl-35334098

RESUMEN

Mechanical ventilation may cause ventilator-induced lung injury (VILI) in patients requiring ventilator support. Inhibition of autophagy is an important approach to ameliorate VILI as it always enhances lung injury after exposure to various stress agents. This study aimed to further reveal the potential mechanisms underlying the effects of geranylgeranyl diphosphate synthase large subunit 1 (GGPPS1) knockout and autophagy in VILI using C57BL/6 mice with lung-specific GGPPS1 knockout that were subjected to mechanical ventilation. The results demonstrate that GGPPS1 knockout mice exhibit significantly attenuated VILI based on the histologic score, the lung wet-to-dry ratio, total protein levels, neutrophils in bronchoalveolar lavage fluid, and reduced levels of inflammatory cytokines. Importantly, the expression levels of autophagy markers were obviously decreased in GGPPS1 knockout mice compared with wild-type mice. The inhibitory effects of GGPPS1 knockout on autophagy were further confirmed by measuring the ultrastructural change of lung tissues under transmission electron microscopy. In addition, knockdown of GGPPS1 in RAW264.7 cells reduced cyclic stretch-induced inflammation and autophagy. The benefits of GGPPS1 knockout for VILI can be partially eliminated through treatment with rapamycin. Further analysis revealed that Rab37 was significantly downregulated in GGPPS1 knockout mice after mechanical ventilation, while it was highly expressed in the control group. Simultaneously, Rab37 overexpression significantly enhances autophagy in cells that are treated with cyclin stretch, including GGPPS1 knockout cells. Collectively, our results indicate that GGPPS1 knockout results in reduced expression of Rab37 proteins, further restraining autophagy and VILI.


Asunto(s)
Lesión Pulmonar Inducida por Ventilación Mecánica , Animales , Autofagia/genética , Dimetilaliltranstransferasa , Farnesiltransferasa , Geraniltranstransferasa , Humanos , Pulmón/metabolismo , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Lesión Pulmonar Inducida por Ventilación Mecánica/genética , Lesión Pulmonar Inducida por Ventilación Mecánica/metabolismo , Lesión Pulmonar Inducida por Ventilación Mecánica/patología , Proteínas de Unión al GTP rab/genética , Proteínas de Unión al GTP rab/metabolismo
16.
Front Pharmacol ; 13: 798436, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35237161

RESUMEN

Doxorubicin (Dox) is a chemotherapeutic drug used to treat a wide range of cancers, but its clinical application is limited due to its cardiotoxicity. Protein kinase C-ζ (PKC-ζ) is a serine/threonine kinase belonging to atypical protein kinase C (PKC) subfamily, and is activated by its phosphorylation. We and others have reported that PKC-ζ induced cardiac hypertrophy by activating the inflammatory signaling pathway. This study focused on whether PKC-ζ played an important role in Dox-induced cardiotoxicity. We found that PKC-ζ phosphorylation was increased by Dox treatment in vivo and in vitro. PKC-ζ overexpression exacerbated Dox-induced cardiotoxicity. Conversely, knockdown of PKC-ζ by siRNA relieved Dox-induced cardiotoxicity. Similar results were observed when PKC-ζ enzyme activity was inhibited by its pseudosubstrate inhibitor, Myristoylated. PKC-ζ interacted with ß-catenin and inhibited Wnt/ß-catenin signaling pathway. Activation of Wnt/ß-catenin signaling by LiCl protected against Dox-induced cardiotoxicity. The Wnt/ß-catenin inhibitor XAV-939 aggravated Dox-caused decline of ß-catenin and cardiomyocyte apoptosis and mitochondrial damage. Moreover, activation of Wnt/ß-catenin suppressed aggravation of Dox-induced cardiotoxicity due to PKC-ζ overexpression. Taken together, our study revealed that inhibition of PKC-ζ activity was a potential cardioprotective approach to preventing Dox-induced cardiac injury.

17.
J Chromatogr A ; 1666: 462858, 2022 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-35124359

RESUMEN

A switchable deep eutectic solvent-based liquid-phase microextraction was proposed and applied to the preconcentration and determination of liposoluble quality-markers of diterpenoid quinones (dihydrotanshinone I, cryptotanshinone, tanshinone I, and tanshinone IIA) in traditional Chinese medicine coupled with high performance liquid chromatography-ultraviolet detection. In the procedure, the hydrophilic deep eutectic solvent of diethanolamine-hexanoic acid (molar ratio 1:1) was prepared and added into the sample phase as an extractant, and a homogeneous solution was formed under slight vortex stirring. After the addition of HCl solution, the deep eutectic solvent miscible with the sample phase was converted to hydrophobic form, and a cloudy solution was generated. Then, the upper hydrophobic layer enriching the target analytes was collected through centrifugation for high performance liquid chromatography analysis. Several critical parameters affecting the extraction performance including the composition and consumption of switchable deep eutectic solvent, the type and amount of acid, salt amount and extraction time were investigated and optimized. Moreover, the structures of the deep eutectic solvent and the recovered hydrophobic layer were both characterized using Fourier transform infrared spectroscopy, further demonstrating the switching mechanism of the extractant during the extraction process. Under the optimal conditions, enrichment factors of diterpenoid quinones ranged from 59 to 274. Good linearities (r≥0.9963), low detection limits (0.5-0.7 ng/mL), satisfactory precisions (relative standard deviations 0.5%-8.6%) and accuracies (recoveries 94.6%-104.6%) were also obtained. Comparing the proposed switchable deep eutectic solvent-based liquid-phase microextraction with other published methods, the characteristics of the procedure were summarized. The developed method was successfully applied for the preconcentration of four liposoluble diterpenoid quinones from a traditional Chinese herbal medicine of Salvia Miltiorrhiza.


Asunto(s)
Microextracción en Fase Líquida , Salvia miltiorrhiza , Disolventes Eutécticos Profundos , Furanos , Límite de Detección , Microextracción en Fase Líquida/métodos , Fenantrenos , Quinonas , Solventes/química
18.
Mod Rheumatol ; 32(5): 974-979, 2022 Aug 20.
Artículo en Inglés | MEDLINE | ID: mdl-34918121

RESUMEN

OBJECTIVES: The study aims to investigate the clinical significance of platelet to albumin ratio (PAR), neutrophil to albumin ratio (NAR), and monocyte to albumin ratio (MAR) in axial spondyloarthritis (axSpA). METHODS: Two hundred and ninety-seven axSpA patients and 71 healthy volunteers were recruited. AxSpA patients were divided into inactive group and active group. Spearman's correlation, receiver operating characteristic (ROC) curves, and binary logistic regression analysis were conducted. RESULTS: Albumin was lower in axSpA group, while neutrophil, platelet, monocyte, NAR, PAR, and MAR were higher (p < .05). Albumin was negatively correlated with BASDAI and BASFI (p < .05). Platelet, NAR, PAR, MAR, ESR, and CRP were all positively correlated with BASDAI and BASFI (p < .05). Albumin was lower in axSpA of active group, while platelet, NAR, PAR, MAR, ESR, and CRP were higher (p < .05). ROC curve indicated that the AUC of PAR for axSpA of active group was higher than that of other variables. The optimal cut-off value of PAR was 6.354, with Youden index of 0.337, specificity of 55.4%, and sensitivity of 78.4%. Logistic regression analysis result suggested that PAR was an independent indicator for axSpA disease activity. CONCLUSIONS: PAR had a high diagnostic value for axSpA of active group. PAR was a novel and reliable indicator for axSpA disease activity.


Asunto(s)
Espondiloartritis Axial , Espondiloartritis , Espondilitis Anquilosante , Albúminas , Plaquetas , Humanos , Curva ROC , Espondiloartritis/diagnóstico , Espondilitis Anquilosante/diagnóstico
19.
Int J Biol Sci ; 17(12): 3048-3058, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34421349

RESUMEN

Metastasis is a key factor that affects the prognosis of colorectal cancer (CRC), and patients with metastasis have limited treatment options and poor prognoses. EGF, latrophilin, and seven transmembrane domains containing 1 (ELTD1/ADGRL4) are members of the adhesion G protein-coupled receptor (aGPCR) superfamily. In this study, high expression of ELTD1 was correlated with lymph node metastasis and poor outcomes in CRC patients. Both in vitro and in vivo studies showed that ELTD1 markedly promoted the invasion and metastasis of CRC. Moreover, ELTD1 accelerated the transcriptional activity of MMP2, which could rescue the impaired invasiveness of CRC cells caused by the downregulation of ELTD1 expression. In conclusion, our study suggests that ELTD1 might be a potential novel target for the treatment of CRC metastasis.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias Colorrectales/patología , Metaloproteinasa 2 de la Matriz/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animales , Línea Celular Tumoral , Neoplasias Colorrectales/metabolismo , Femenino , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Desnudos , Persona de Mediana Edad , Invasividad Neoplásica , Metástasis de la Neoplasia , Activación Transcripcional
20.
Sci Prog ; 104(2): 368504211009368, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33861664

RESUMEN

Sand transport is the main manifestation of sand damage in the arid and semiarid regions globally. It is a huge challenge to stabilize mobile sandy and change them into stable productive ecosystems. The establishment of simulated shrubs is one of the most effective measures to solve the above difficulties as a novel sand-barrier. To clarify simulated shrubs' role in the process of ecological restoration. It will be greatly helpful to incorporate the shelter device proposed in the present work into landscape models for aeolian soil transport, to optimize the parameters associated with the sand-barrier characteristics for aeolian soil stabilization at the field scale. A series of wind tunnel experiments were conducted to analyze the variations of soil grain-size of simulated shrubs with different spatial configurations, row spaces, and net wind speeds. Further, the soil grain-size parameters were calculated by the classic method proposed by Folk and Ward to clarify the change of soil particles resulted from the blocking effects. The average grain-size content of simulated shrubs with different spatial configurations, row spaces, and net wind speeds was dominated by medium sand and fine sand, and the total percentage was more than 90%. Moreover, the sand deposition of simulated shrubs with different spatial configurations increased with the improvement of wind speeds. The average sand deposition of spindle-shaped simulated shrubs in 17.5 × 17.5 cm and broom-shaped simulated shrubs in 17.5 × 26.25 cm under different net wind speeds was the least. The effects of row spaces on average grain-size parameters increased with the improvement of net wind speeds. By calculating the correct characteristics of specific shelter devices proposed in the present work, all of these findings suggest that the application of simulated shrubs will be an important component to further extend ecological engineering projects in arid and semiarid regions.


Asunto(s)
Ecosistema , Arena , Suelo
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