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1.
Environ Sci Ecotechnol ; 21: 100422, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38746775

RESUMEN

Remediating soil contaminated with polycyclic aromatic hydrocarbons (PAHs) presents a significant environmental challenge due to their toxic and carcinogenic properties. Traditional PAHs remediation methods-chemical, thermal, and bioremediation-along with conventional soil-washing agents like surfactants and cyclodextrins face challenges of cost, ecological harm, and inefficiency. Here we show an effective and environmentally friendly calixarene derivative for PAHs removal through soil washing. Thiacalix[4]arene tetrasulfonate (TCAS) has a unique molecular structure of a sulfonate group and a sulfur atom, which enhances its solubility and facilitates selective binding with PAHs. It forms host-guest complexes with PAHs through π-π stacking, OH-π interactions, hydrogen bonding, van der Waals forces, and electrostatic interactions. These interactions enable partial encapsulation of PAH molecules, aiding their desorption from the soil matrix. Our results show that a 0.7% solution of TCAS can extract approximately 50% of PAHs from contaminated soil while preserving soil nutrients and minimizing adverse environmental effects. This research unveils the pioneering application of TCAS in removing PAHs from contaminated soil, marking a transformative advancement in resource-efficient and sustainable soil remediation strategies.

2.
Biomed Pharmacother ; 175: 116653, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38688172

RESUMEN

Huangqi Guizhi Wuwu Decoction (HQGZWWD) has shown promising potential in treating various cardiovascular diseases. This study aimed to elucidate the molecular basis and therapeutic role of HQGZWWD in the treatment of doxorubicin (DOX)-induced myocardial injury. The HPLC fingerprint of HQGZWWD was used to analyze the active components. A DOX-induced myocardial damage rat model was developed, and the therapeutic effects of HQGZWWD were evaluated using echocardiography, myocardial enzyme levels, and hematoxylin and eosin staining. Network pharmacology was used to screen treatment targets, and western blotting and immunohistochemistry were performed to assess cellular pyroptosis levels. Oxidative stress levels were measured using assay kits, and mitochondrial damage was examined using transmission electron microscopy. An in vitro model of DOX-induced cell damage was established, and treatment was administered using serum containing HQGZWWD and N-acetylcysteine (NAC). Oxidative stress levels were detected using assay kits and DCFH-DA, whereas cellular pyroptosis levels were assessed through WB, immunofluorescence, and ELISA assays. HQGZWWD ameliorated DOX-induced myocardial injury. Network pharmacology identified IL-1ß and IL-18 as crucial targets. HQGZWWD downregulated the protein levels of the inflammatory factors IL-1ß and IL-18, inhibited the expression of GSDMD-NT, and simultaneously suppressed the synthesis of Caspase-1, ASC, NLRP3, and Caspase-11. Additionally, HQGZWWD inhibited oxidative stress, and the use of NAC as an oxidative stress inhibitor resulted in significant inhibition of the GSDMD-NT protein in H9C2 cells. These findings highlight the myocardial protective effects of HQGZWWD by inhibiting oxidative stress and suppressing both canonical and non-canonical pyroptotic pathways.


Asunto(s)
Cardiotoxicidad , Doxorrubicina , Medicamentos Herbarios Chinos , Estrés Oxidativo , Piroptosis , Ratas Sprague-Dawley , Animales , Doxorrubicina/toxicidad , Piroptosis/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Estrés Oxidativo/efectos de los fármacos , Cardiotoxicidad/tratamiento farmacológico , Cardiotoxicidad/metabolismo , Cardiotoxicidad/prevención & control , Ratas , Masculino , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Línea Celular , Farmacología en Red
3.
Int J Mol Sci ; 25(7)2024 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-38612440

RESUMEN

Salinity is one of the most serious threats to sustainable agriculture. The Salt Overly Sensitive (SOS) signaling pathway plays an important role in salinity tolerance in plants, and the SOS2 gene plays a critical role in this pathway. Mulberry not only has important economic value but also is an important ecological tree species; however, the roles of the SOS2 gene associated with salt stress have not been reported in mulberry. To gain insight into the response of mulberry to salt stress, SOS2 (designated MulSOS2) was cloned from mulberry (Morus atropurpurea Roxb), and sequence analysis of the amino acids of MulSOS2 showed that it shares some conserved domains with its homologs from other plant species. Our data showed that the MulSOS2 gene was expressed at different levels in different tissues of mulberry, and its expression was induced substantially not only by NaCl but also by ABA. In addition, MulSOS2 was exogenously expressed in Arabidopsis, and the results showed that under salt stress, transgenic MulSOS2 plants accumulated more proline and less malondialdehyde than the wild-type plants and exhibited increased tolerance to salt stress. Moreover, the MulSOS2 gene was transiently overexpressed in mulberry leaves and stably overexpressed in the hairy roots, and similar results were obtained for resistance to salt stress in transgenic mulberry plants. Taken together, the results of this study are helpful to further explore the function of the MulSOS2 gene, which provides a valuable gene for the genetic breeding of salt tolerance in mulberry.


Asunto(s)
Arabidopsis , Morus , Tolerancia a la Sal/genética , Morus/genética , Fitomejoramiento , Estrés Salino , Agricultura , Plantas Modificadas Genéticamente
4.
Sleep Med ; 117: 177-183, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38554533

RESUMEN

OBJECTIVES: To explore the relationship between nocturnal levels of stress-related hormones and different sleep-wake states in chronic insomnia disorder (CID) patients. METHODS: Thirty-three CID patients and 34 good sleepers were enrolled and completed assessment of sleep log, Pittsburgh Sleep Quality Index and Insomnia Severity Index. During a-overnight polysomnography monitoring, the patients' vein bleeds were continually collected at different time points (pre-sleep, deep-sleep, 5-min or 30-min waking, and morning waking-up). The control subjects' bleeds were collected only at 22:00 and morning waking-up. The serum hormones were detected using enzyme-linked immunosorbent assay. RESULTS: Compared with at pre-sleep, the level of cortisol was significantly higher at morning waking-up respectively in two-group subjects (Ps < 0.001), with insignificant inter-group differences in cortisol, corticotropin releasing hormone and copeptin at the two time-points. In the patients, the nocturnal secretion curves of three hormones were similar, with the highest concentration at morning waking-up, followed by 30-min waking, 5-min waking, pre-sleep, and deep-sleep. The patients' cortisol (Z = 79.192, P < 0.001) and copeptin (Z = 12.333, P = 0.015) levels were statistically different at different time-points, with higher cortisol at morning waking-up relative to deep-sleep, pre-sleep and 5-min waking (Ps < 0.05), and at 30-min waking relative to deep-sleep and pre-sleep (Ps < 0.05), and higher copeptin at morning waking-up relative to deep-sleep (P < 0.05). CONCLUSIONS: In CID, the nocturnal wakes were instantaneously accompanied by high level, and deep sleep was accompanied by the lowest levels, of stress-related hormones, especially in cortisol, supporting the insomniac hypothesis of increased nocturnal pulse-release of cortisol.


Asunto(s)
Trastornos del Inicio y del Mantenimiento del Sueño , Humanos , Proyectos Piloto , Hidrocortisona , Sueño , Polisomnografía
5.
Sci Rep ; 14(1): 1587, 2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-38238387

RESUMEN

In order to explore the mechanism of rockburst in coal seam with rock parting, a combination of on-site and numerical experiment is used to study the failure and instability process, crack propagation mechanism, and influencing factors. The following four points were addressed: (1) the instability is a process that roadway in coal seam with rock parting go through from stable locking in the initial stress unloading stage to slipping unlocking, and then to spatter ejection in slipping dynamic load disturbance stage. (2) The fracture development caused by unloading excavation of coal seam with rock parting will change from shear crack to tensile crack. In this process, coal-rock contact surface slip and coal-rock fracture are coupled with each other. (3) The greater the mining depth is, the greater the lateral pressure coefficient is, and the higher the rockburst risk is. On the contrary, the lower the risk of rockburst. (4) When choosing the support form of roadway in coal seam with rock parting, the two supporting forms of bolting (cable) and supplementary masonry support should be preferred. The results enrich the theory of the dynamics of surrounding rock fracture in coal mine, further clarify the potential dangers to mining-area roadways and working faces, and provide technical information to ensure the safe and efficient mining of bifurcated coal seam.

6.
Medicine (Baltimore) ; 103(1): e36304, 2024 Jan 05.
Artículo en Inglés | MEDLINE | ID: mdl-38181297

RESUMEN

BACKGROUND: This study aimed to observe clinical efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) gel, medical collagen sponge and rhGM-CSF gel in combination with medical collagen sponge on deep second-degree burns of head, face or neck in infants. METHODS: A total of 108 infants with deep second-degree burns on head, face or neck were randomly divided into rhGM-CSF group, medical collagen sponge group, and rhGM-CSF + medical collagen sponge group. The scab dissolving time, healing time, bacterial positive rate and Vancouver scar scale were evaluated and analyzed. RESULTS: The data analysis showed that scab dissolving time and healing time were shorter in rhGM-CSF + medical collagen sponge group than that in rhGM-CSF group and medical collagen sponge group, and the difference was statistically significant (P < .05). Bacterial positive rate was lower in rhGM-CSF + medical collagen sponge group than that in rhGM-CSF group and medical collagen sponge group (P < .05). After 3 months, score of Vancouver scar scale (scar thickness, pliability, pigmentation and vascularity) was less in rhGM-CSF + medical collagen sponge group than that in rhGM-CSF group and medical collagen sponge group (P < .05). CONCLUSION: rhGM-CSF gel in combination with medical collagen sponge is significantly effective in treating deep second-degree burns of head, face or neck in infants. This combination is beneficial for infection control, acceleration of scab dissolving and wound healing, and reduction of scar hyperplasia and pigmentation, which is worthy of clinical application and promotion.


Asunto(s)
Quemaduras , Cicatriz , Lactante , Humanos , Colágeno/uso terapéutico , Resultado del Tratamiento , Quemaduras/tratamiento farmacológico
7.
Artículo en Inglés | MEDLINE | ID: mdl-38175414

RESUMEN

The objective of this study is to examine the potential protective effect of rosmarinic acid (RosA) encapsulated within nanoliposomes (RosA-LIP) on hepatic damage induced by iron overload. The characteristics, stability, and release of RosA-LIP in vitro were identified. The mice were randomly assigned to five groups: Control, Model, Model+DFO (DFO), Model+RosA (RosA), and Model+RosA-LIP (RosA-LIP). The iron overload model was induced by administering iron dextran (i.p.). The DFO, RosA, and RosA-LIP groups received iron dextran and were subsequently treated with DFO, RosA, and RosA-LIP for 14 days. We developed a novel formulation of RosA-LIP that exhibited stability and controlled release properties. Firstly, RosA-LIP improved liver function and ameliorated pathological changes in a mouse model of iron overload. Secondly, RosA-LIP demonstrated the ability to enhance the activities of T-SOD, GSH-Px, and CAT, while reducing the levels of MDA and 4-HNE, thereby effectively mitigating oxidative stress damage induced by iron overload. Thirdly, RosA-LIP reduced hepatic iron levels by downregulating FTL, FTH, and TfR1 levels. Additionally, RosA-LIP exerted a suppressive effect on hepcidin expression through the BMP6-SMAD1/5/8 signaling pathway. Furthermore, RosA-LIP upregulated FPN1 expression in both the liver and duodenum, thereby alleviating iron accumulation in these organs in mice with iron overload. Notably, RosA exhibited a comparable iron chelation effect, and RosA-LIP demonstrated superior efficacy in mitigating liver damage induced by excessive iron overload. RosA-LIP exhibited favorable sustained release properties, targeted delivery, and efficient protection against iron overload-induced liver damage. A schematic representation of the proposed protective mechanism of rosmarinic acid liposome during iron overload. Once RosA-LIP is transported into cells, RosA is released. On the one hand, RosA attenuates the BMP6-SMAD1/5/8-SMAD4 signaling pathway activation, leading to inhibiting hepcidin transcription. Then, the declined hepcidin contacted the inhibitory effect of FPN1 in hepatocytes and duodenum, increasing iron mobilization. On the other hand, RosA inhibits TfR1 and ferritin expression, which decreases excessive iron and oxidative damage.

8.
Biochim Biophys Acta Mol Basis Dis ; 1870(3): 166944, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-37952827

RESUMEN

Sema4D (CD100) is closely related to pathological and physiological processes, including tumor growth, angiogenesis and cardiac development. Nevertheless, the role and mechanism of Sema4D in cardiac hypertrophy are still unclear to date. To assess the impact of Sema4D on pathological cardiac hypertrophy, TAC surgery was performed on C57BL/6 mice which were transfected with AAV9-mSema4D-shRNA or AAV9-mSema4D adeno-associated virus by tail vein injection. Our results indicated that Sema4D knockdown mitigated cardiac hypertrophy, fibrosis and dysfunction when exposed to pressure overload, and Sema4D downregulation markedly inhibited cardiomyocyte hypertrophy induced by angiotensin II. Meanwhile, Sema4D overexpression had the opposite effect in vitro and in vivo. Furthermore, analysis of signaling pathways showed that Sema4D activated the MAPK pathway during cardiac hypertrophy induced by pressure overload, and the pharmacological mitogen-activated protein kinase kinase 1/2 inhibitor U0126 almost completely reversed Sema4D overexpression-induced deteriorated phenotype, resulting in improved cardiac function. Further research indicated that myocardial hypertrophy induced by Sema4D was closely related to the expression of the pyroptosis-related proteins PP65, NLRP3, caspase-1, ASC, GSDMD, IL-18 and IL-1ß. In conclusion, our study demonstrated that Sema4D regulated the process of pathological myocardial hypertrophy through modulating MAPK/NF-κB/NLRP3 pathway, and Sema4D may be the promising interventional target of cardiac hypertrophy and heart failure.


Asunto(s)
Antígenos CD , Miocitos Cardíacos , FN-kappa B , Semaforinas , Animales , Ratones , Cardiomegalia/metabolismo , Ratones Endogámicos C57BL , Miocitos Cardíacos/metabolismo , FN-kappa B/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo
9.
Acta Pharmacol Sin ; 45(2): 405-421, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37814123

RESUMEN

Gastric cancer stem cells (GCSCs) contribute to the refractory features of gastric cancer (GC) and are responsible for metastasis, relapse, and drug resistance. The key factors drive GCSC function and affect the clinical outcome of GC patients remain poorly understood. PRSS23 is a novel serine protease that is significantly up-regulated in several types of cancers and cancer stem cells, and related to tumor progression and drug resistance. In this study, we investigated the role of PRSS23 in GCSCs as well as the mechanism by which PRSS23 regulated the GCSC functions. We demonstrated that PRSS23 was critical for sustaining GCSC survival. By screening a collection of human immunodeficiency virus (HIV) protease inhibitors (PIs), we identified tipranavir as a PRSS23-targeting drug, which effectively killed both GCSC and GC cell lines (its IC50 values were 4.7 and 6.4 µM in GCSC1 cells and GCSC2 cells, respectively). Administration of tipranavir (25 mg·kg-1·d-1, i.p., for 8 days) in GCSC-derived xenograft mice markedly inhibited the growth of subcutaneous GCSC tumors without apparent toxicity. In contrast, combined treatment with 5-FU plus cisplatin did not affect the tumor growth but causing significant weight loss. Furthermore, we revealed that tipranavir induced GCSC cell apoptosis by suppressing PRSS23 expression, releasing MKK3 from the PRSS23/MKK3 complex to activate p38 MAPK, and thereby activating the IL24-mediated Bax/Bak mitochondrial apoptotic pathway. In addition, tipranavir was found to kill other types of cancer cell lines and drug-resistant cell lines. Collectively, this study demonstrates that by targeting both GCSCs and GC cells, tipranavir is a promising anti-cancer drug, and the clinical development of tipranavir or other drugs specifically targeting the PRSS23/MKK3/p38MAPK-IL24 mitochondrial apoptotic pathway may offer an effective approach to combat gastric and other cancers.


Asunto(s)
Piridinas , Pironas , Neoplasias Gástricas , Sulfonamidas , Humanos , Animales , Ratones , Neoplasias Gástricas/patología , Línea Celular Tumoral , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Células Madre Neoplásicas , Apoptosis , Serina Endopeptidasas/metabolismo
10.
Bioresour Technol ; 393: 130081, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37993067

RESUMEN

The sulfur fluidizing bioreactor (S0FB) has significant superiorities in treating nitrate-rich wastewater. However, substantial self-acidification has been observed in engineering applications, resulting in frequent start-up failures. In this study, self-acidification was reproduced in a lab-scale S0FB. It was demonstrated that self-acidification was mainly induced by sulfur disproportionation process, accounting for 93.4 % of proton generation. Supplying sufficient alkalinity to both the influent (3000 mg/L) and the bulk (2000 mg/L) of S0FB was essential for achieving a successful start-up. Furthermore, the S0FB reached 10.3 kg-N/m3/d of nitrogen removal rate and 0.13 kg-PO43-/m3/d of phosphate removal rate, respectively, surpassing those of the documented sulfur packing bioreactors by 7-129 times and 26-65 times. This study offers a feasible and practical method to avoid self-acidification during restart of S0FB and highlights the considerable potential of S0FB in the treatment of nitrate-rich wastewater.


Asunto(s)
Nitratos , Aguas Residuales , Procesos Autotróficos , Desnitrificación , Azufre , Reactores Biológicos , Concentración de Iones de Hidrógeno , Nitrógeno
11.
Adv Sci (Weinh) ; 11(4): e2305442, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38009491

RESUMEN

Neuroinflammation is associated with poor outcomes in patients with spinal cord injury (SCI). Recent studies have demonstrated that stimulator of interferon genes (Sting) plays a key role in inflammatory diseases. However, the role of Sting in SCI remains unclear. In the present study, it is found that increased Sting expression is mainly derived from activated microglia after SCI. Interestingly, knockout of Sting in microglia can improve the recovery of neurological function after SCI. Microglial Sting knockout restrains the polarization of microglia toward the M1 phenotype and alleviates neuronal death. Furthermore, it is found that the downregulation of mitofusin 2 (Mfn2) expression in microglial cells leads to an imbalance in mitochondrial fusion and division, inducing the release of mitochondrial DNA (mtDNA), which mediates the activation of the cGas-Sting signaling pathway and aggravates inflammatory response damage after SCI. A biomimetic microglial nanoparticle strategy to deliver MASM7 (named MSNs-MASM7@MI) is established. In vitro, MSNs-MASM7@MI showed no biological toxicity and effectively delivered MASM7. In vivo, MSNs-MASM7@MI improves nerve function after SCI. The study provides evidence that cGas-Sting signaling senses Mfn2-dependent mtDNA release and that its activation may play a key role in SCI. These findings provide new perspectives and potential therapeutic targets for SCI treatment.


Asunto(s)
Microglía , Traumatismos de la Médula Espinal , Humanos , Microglía/metabolismo , ADN Mitocondrial/genética , ADN Mitocondrial/metabolismo , Regulación hacia Abajo , Inflamación/metabolismo , Traumatismos de la Médula Espinal/metabolismo , Nucleotidiltransferasas/metabolismo
12.
Food Chem ; 440: 138244, 2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38142554

RESUMEN

Flusilazole is a triazole fungicide with residues that are potentially toxic to humans. It enters the human body mainly through food, although its bactericidal activity is substantial. In this study, an electrochemical sensor Fe/Fe2O3@C with a core-shell structure was constructed to efficiently detect flusilazole by annealing MIL-53(Fe) which was prepared by a simple solvothermal method. Transmission electron microscopy and scanning electron microscopy were used to characterize the apparent morphology of MIL-53(Fe) and Fe/Fe2O3@C, and their structures were further characterized by X-ray photoelectron spectroscopy, Raman spectroscopy, powder X-ray diffraction, and the mapping of elements by energy dispersive spectroscopy. The electrochemical behavior of Fe/Fe2O3@C in the detection of flusilazole was evaluated by differential pulse voltammetry under optimal conditions. The results of the study indicate that the Fe/Fe2O3@C electrochemical sensor displayed excellent detection capabilities for flusilazole, where the sensor exhibited a wide detection range from 1.00 × 10-4 to 1.00 × 10-12 mol/L with an incredibly low LOD of 593 fM, making it highly sensitive to trace amounts of flusilazole. Moreover, Fe/Fe2O3@C demonstrated superior reproducibility, stability, and resistance to interference, highlighting its reliability in practical applications. The sensor was also successfully utilized to quantitatively detect flusilazole in various real samples, which suggests that Fe/Fe2O3@C has broad-spectrum environmental resistance and can effectively and rapidly detect flusilazole residues in different types of food items and environmental matrices. The study also delved into the mechanism of Fe/Fe2O3@C for the detection of flusilazole, providing a deeper understanding of the functionality of this sensor. Overall, these findings emphasize the practical significance of Fe/Fe2O3@C as an electrochemical sensor, showcasing its potential for real-world applications in food safety and environmental monitoring.


Asunto(s)
Inocuidad de los Alimentos , Silanos , Triazoles , Humanos , Reproducibilidad de los Resultados , Microscopía Electrónica de Rastreo , Técnicas Electroquímicas/métodos
13.
Acta Pharm Sin B ; 13(12): 4765-4784, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38045042

RESUMEN

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.

14.
Artículo en Inglés | MEDLINE | ID: mdl-38094099

RESUMEN

Background: Diabetic kidney disease (DKD) is a serious microvascular complication of diabetes that affects both type 1 and type 2 diabetes patients at a high incidence rate. Naja Naja atra venom (NNAV) has been shown to have protective effects and improved renal function in diabetic rats. However, its mechanism of action is still unclear. This study aims to unravel the effectiveness and mechanisms of NNAV on DKD. Methods: We conducted in vitro experiments in which Human Kidney-2 (HK-2) cells were stimulated with high glucose, and exposed to varying concentrations of NNAV. Cell morphology, as well as α-SMA, TGF-ß1, and E-cadherin levels, were analyzed using immunofluorescence and western blot. In vivo experiments involved a diabetic rat model, where varying concentrations of cobra α-neurotoxin (CTX) were administrated via gastric treatment. We observed and noted pathomorphological changes, measured biochemical and oxidative stress indices, and used western blot to assess podocin and nephrin levels. Results: High glucose levels can induce a decrease in E-cadherin expression and an increase in α-SMA and transforming growth factor-ß1 (TGF-ß1) expression in HK-2 cells. NNAV can inhibit the transdifferentiation of HK-2 cells to myofibroblast (MyoF) in a high glucose environment and reduce the expression of TGF-ß1. Cobra α-neurotoxin (CTX) can reduce urine protein in diabetes model rats at an early stage, which is dose-independent and has a time application range. CTX can regulate the expression of nephrin and podocin. Conclusion: The present study indicates that CTX and NNAV attenuate STZ and high glucose-induced DKD. Its mechanisms of action are associated with inhibiting oxidative stress and TEMT. The study suggests that NNAV and CTX might be a potential therapeutic drug for treating DKD.

15.
J Agric Food Chem ; 71(51): 20680-20689, 2023 Dec 27.
Artículo en Inglés | MEDLINE | ID: mdl-38088263

RESUMEN

The black cutworm Agrotis ipsilon is a serious crop pest. Phoxim, an organophosphorus insecticide, has been widely used to control A. ipsilon. When phoxim is extensively applied, the susceptibility of A. ipsilon to insecticide is reduced. However, the mechanisms of tolerance of A. ipsilon to phoxim remain unclear. Herein, we report that an epsilon class glutathione S-transferase, AiGSTE1, confers phoxim tolerance in A. ipsilon. Exposure to a sublethal concentration (LC50) of phoxim caused oxidative stress and activated the transcription of AiGSTe1 genes in A. ipsilon larvae. Recombinant AiGSTE1 expressed in Escherichia coli could metabolize phoxim. Furthermore, E. coli cells overexpressing AiGSTE1 displayed significant tolerance to oxidative stress. Knockdown of AiGSTe1 by RNA interference significantly increased the mortality of A. ipsilon larvae to phoxim. These results demonstrate that AiGSTE1 confers phoxim tolerance in A. ipsilon by metabolizing the insecticide and preventing phoxim-induced oxidative stress.


Asunto(s)
Insecticidas , Lepidópteros , Mariposas Nocturnas , Animales , Insecticidas/farmacología , Escherichia coli/genética , Compuestos Organofosforados , Mariposas Nocturnas/genética , Larva/genética
16.
Am J Cancer Res ; 13(8): 3517-3530, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37693159

RESUMEN

Patients with non-small cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors (TKIs) inevitably exhibit drug resistance, which diminishes therapeutic effects. Nonetheless, the molecular mechanisms of TKI resistance in NSCLC remain obscure. In this study, data from clinical and TCGA databases revealed an increase in DNMT3A expression, which was correlated with a poor prognosis. Using NSCLC organoid models, we observed that high DNMT3A levels reduced TKI susceptibility of NSCLC cells via upregulating inhibitor of apoptosis proteins (IAPs). Simultaneously, the DNMT3Ahigh subset, which escaped apoptosis, underwent an early senescent-like state in a CDKN1A-dependent manner. Furthermore, the cellular senescence induced by TKIs was observed to be reversible, whereas DNMT3Ahigh cells reacquired their proliferative characteristics in the absence of TKIs, resulting in subsequent tumour recurrence and growth. Notably, the blockade of DNMT3A/IAPs signals enhanced the efficacy of TKIs in DNMT3Ahigh tumour-bearing mice, which represented a promising strategy for the effective treatment of NSCLC.

17.
BMC Med Inform Decis Mak ; 23(1): 169, 2023 08 29.
Artículo en Inglés | MEDLINE | ID: mdl-37644543

RESUMEN

INTRODUCTION: The COVID-19 patients in the convalescent stage noticeably have pulmonary diffusing capacity impairment (PDCI). The pulmonary diffusing capacity is a frequently-used indicator of the COVID-19 survivors' prognosis of pulmonary function, but the current studies focusing on prediction of the pulmonary diffusing capacity of these people are limited. The aim of this study was to develop and validate a machine learning (ML) model for predicting PDCI in the COVID-19 patients using routinely available clinical data, thus assisting the clinical diagnosis. METHODS: Collected from a follow-up study from August to September 2021 of 221 hospitalized survivors of COVID-19 18 months after discharge from Wuhan, including the demographic characteristics and clinical examination, the data in this study were randomly separated into a training (80%) data set and a validation (20%) data set. Six popular machine learning models were developed to predict the pulmonary diffusing capacity of patients infected with COVID-19 in the recovery stage. The performance indicators of the model included area under the curve (AUC), Accuracy, Recall, Precision, Positive Predictive Value(PPV), Negative Predictive Value (NPV) and F1. The model with the optimum performance was defined as the optimal model, which was further employed in the interpretability analysis. The MAHAKIL method was utilized to balance the data and optimize the balance of sample distribution, while the RFECV method for feature selection was utilized to select combined features more favorable to machine learning. RESULTS: A total of 221 COVID-19 survivors were recruited in this study after discharge from hospitals in Wuhan. Of these participants, 117 (52.94%) were female, with a median age of 58.2 years (standard deviation (SD) = 12). After feature selection, 31 of the 37 clinical factors were finally selected for use in constructing the model. Among the six tested ML models, the best performance was accomplished in the XGBoost model, with an AUC of 0.755 and an accuracy of 78.01% after experimental verification. The SHAPELY Additive explanations (SHAP) summary analysis exhibited that hemoglobin (Hb), maximal voluntary ventilation (MVV), severity of illness, platelet (PLT), Uric Acid (UA) and blood urea nitrogen (BUN) were the top six most important factors affecting the XGBoost model decision-making. CONCLUSION: The XGBoost model reported here showed a good prognostic prediction ability for PDCI of COVID-19 survivors during the recovery period. Among the interpretation methods based on the importance of SHAP values, Hb and MVV contributed the most to the prediction of PDCI outcomes of COVID-19 survivors in the recovery period.


Asunto(s)
COVID-19 , Capacidad de Difusión Pulmonar , Humanos , Femenino , Persona de Mediana Edad , Masculino , Estudios de Seguimiento , Área Bajo la Curva , Aprendizaje Automático
18.
Cell Death Dis ; 14(8): 545, 2023 08 23.
Artículo en Inglés | MEDLINE | ID: mdl-37612301

RESUMEN

Gastric cancer (GC) is notoriously resistant to current therapies due to tumor heterogeneity. Cancer stem cells (CSCs) possess infinite self-renewal potential and contribute to the inherent heterogeneity of GC. Despite its crucial role in chemoresistance, the mechanism of stemness maintenance of gastric cancer stem cells (GCSCs) remains largely unknown. Here, we present evidence that lengsin, lens protein with glutamine synthetase domain (LGSN), a vital cell fate determinant, is overexpressed in GCSCs and is highly correlated with malignant progression and poor survival in GC patients. Ectopic overexpression of LGSN in GCSC-derived differentiated cells facilitated their dedifferentiation and treatment resistance by interacting with vimentin and inducing an epithelial-to-mesenchymal transition. Notably, genetic interference of LGSN effectively suppressed tumor formation by inhibiting GCSC stemness maintenance and provoking gasdermin-D-mediated pyroptosis through vimentin degradation/NLRP3 signaling. Depletion of LGSN combined with the chemo-drugs 5-fluorouracil and oxaliplatin could offer a unique and promising approach to synergistically rendering this deadly cancer eradicable in vivo. Our data place focus on the role of LGSN in GCSC regeneration and emphasize the critical importance of pyroptosis in battling GCSC.


Asunto(s)
Piroptosis , Neoplasias Gástricas , Humanos , Vimentina , Neoplasias Gástricas/tratamiento farmacológico , Neoplasias Gástricas/genética , Células Madre Neoplásicas
19.
Food Chem ; 428: 136802, 2023 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-37421661

RESUMEN

Diflubenzuron is widely used as a benzoylurea insecticide, and its impact on human health should not be underestimated. Therefore, the detection of its residues in food and the environment is crucial. In this paper, octahedral Cu-BTB was fabricated using a simple hydrothermal method. It served as a precursor for synthesizing Cu/Cu2O/CuO@C with a core-shell structure through annealing, creating an electrochemical sensor for the detection of diflubenzuron. The response of Cu/Cu2O/CuO@C/GCE, expressed as ΔI/I0 exhibited a linear correlation with the logarithm of the diflubenzuron concentration ranging from 1.0 × 10-4 to 1.0 × 10-12 mol·L-1. The limit of detection (LOD) was determined to be 130 fM using differential pulse voltammetry (DPV). The electrochemical sensor demonstrated excellent stability, reproducibility, and anti-interference properties. Moreover, Cu/Cu2O/CuO@C/GCE was successfully employed to quantitatively determine diflubenzuron in actual food samples (tomato and cucumber) and environmental samples (Songhua River water, tap water, and local soil) with good recoveries. Finally, the possible mechanism of Cu/Cu2O/CuO@C/GCE for monitoring diflubenzuron was thoroughly investigated.


Asunto(s)
Diflubenzurón , Humanos , Reproducibilidad de los Resultados , Cobre/química , Agua , Técnicas Electroquímicas/métodos , Electrodos
20.
Heliyon ; 9(2): e11880, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36852077

RESUMEN

Background: There are many pharmaceutical interventions available to prevent osteoporotic vertebral fractures in postmenopausal women, but the efficacy and safety of these drugs are unknown. This study aimed to investigate the efficacy and safety of drugs in the prevention of osteoporotic vertebral fractures. Methods: PubMed, Embase, and the Cochrane Library were comprehensively searched for randomized controlled trials (RCTs) published up to February 15, 2020, including postmenopausal women with osteoporosis. Network meta-analysis was conducted based on the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The relative risk (RR) and 95% confidence interval (CI) were used to report the results. This study was registered with PROSPERO, number CRD42020201167. Main Outcomes were incidences of new vertebral fracture and serious adverse events. Results: Fifty-five RCTs (n = 104 580) evaluating vertebral fractures of sixteen kinds of pharmacologic therapies were included in the network meta-analysis. Abaloparatide (RR, 0.21; [95% CI, 0.09 to 0.51]), alendronate (RR, 0.55; [95% CI, 0.38 to 0.81]), calcitonin (RR, 0.44; [95% CI, 0.25 to 0.78]), denosumab (RR, 0.33; [95% CI, 0.14 to 0.61]), parathyroid hormone (PTH) (RR, 0.32; [95% CI, 0.10 to 0.97]), risedronate (RR, 0.65; [95% CI, 0.42 to 1.00]), romosozumab (RR, 0.31; [95% CI, 0.16 to 0.61]), strontium ranelate (RR, 0.62; [95% CI, 0.42 to 0.93]), teriparatide (RR, 0.27; [95% CI, 0.17 to 0.43]), and zoledronate (RR, 0.41; [95% CI, 0.93]) were associated with lower vertebral fracture risk compared to placebo. PTH was associated with more adverse event rates. For any two drug treatments, the RR of serious adverse events was not statistically significant. Hormone replacement therapy (HRT) and calcitonin may be slower to work because they have only been shown to reduce the risk of vertebral fractures in long-term (>18 months) follow-up. Conclusions: A variety of drugs are safe and effective in preventing osteoporotic vertebral fractures. HRT and calcitonin only reduced the risk of vertebral fractures during a follow-up of 21-72 months.

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