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1.
J Hazard Mater ; 472: 134549, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38733789

RESUMEN

Selenium nanoparticles (SeNPs) has been reported as a beneficial role in alleviating cadmium (Cd) toxicity in plant. However, underlying molecular mechanisms about SeNPs reducing Cd accumulation and alleviating Cd toxicity in wheat are not well understood. A hydroponic culture was performed to evaluate Cd and Se accumulation, cell wall components, oxidative stress and antioxidative system, and transcriptomic response of wheat seedlings after SeNPs addition under Cd stress. Results showed that SeNPs application notably reduced Cd concentration in root and in shoot by 56.9% and 37.3%, respectively. Additionally, SeNPs prompted Cd distribution in root cell wall by 54.7%, and increased lignin, pectin and hemicellulose contents by regulating cell wall biosynthesis and metabolism-related genes. Further, SeNPs alleviated oxidative stress caused by Cd in wheat through signal transduction pathways. We also observed that Cd addition reduced Se accumulation by downregulating the expression level of aquaporin 7. These results indicated that SeNPs alleviated Cd toxicity and reduced Cd accumulation in wheat, which were associated with the synergetic regulation of cell wall biosynthesis pathway, uptake transporters, and antioxidative system via signaling pathways.

2.
RSC Adv ; 14(20): 13694-13702, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38681839

RESUMEN

Currently, the photostability of photosensitizer curcumin is the main bottleneck limiting their application, reducing the bioavailability of curcumin. Studying the effect of different light sources on the photostabilities of curcumin and loading it onto polydopamine nanocarriers with better biocompatibility will help improve its light utilization efficiency. In this study, we investigated the photostabilities of curcumin and a polydopamine-based nanoparticle (polydopamine-curcumin composite nanoparticles, PDA-Cur NPs) loaded with curcumin through in vitro and in vivo experiments to achieve better antitumor effects. The results demonstrated that curcumin has good photostability in dark, but with significant photodegradation rates in both red and blue light. Blue light has a faster effect on the photodegradation of curcumin, with a degradation rate of 42.1% after 10 minutes, which is about 1.7 times that of the red light. Our study successfully synthesized PDA-Cur NPs, demonstrating its ability to stably load and release curcumin, with a loading percentage of 65.7% after 2 hours and 41.9% release in 8 hours (pH 6.0). Compared with single curcumin treatments, the photodegradation rates of PDA-Cur NPs in red and blue light treatments were reduced by 46% and 50%, respectively. Meanwhile, PDA-Cur NPs exhibited remarkable antitumor efficacy due to PDT and promote apoptosis in cancer cells, which both better than that of single curcumin treatments. Moreover, in MCF-7 tumor-bearing mice, the PDA-Cur NPs led to significant tumor growth inhibition effects, without causing evident systemic damage in vivo. The findings highlight the potential of PDA-Cur NPs as anticancer photosensitizer with greatly increased utilization of curcumin in PDT.

3.
Mol Med ; 30(1): 56, 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38671369

RESUMEN

BACKGROUND: Ginsenoside Rh2 (G-Rh2), a steroidal compound extracted from roots of ginseng, has been extensively studied in tumor therapy. However, its specific regulatory mechanism in non-small cell lung cancer (NSCLC) is not well understood. Pyruvate dehydrogenase kinase 4 (PDK4), a central regulator of cellular energy metabolism, is highly expressed in various malignant tumors. We investigated the impact of G-Rh2 on the malignant progression of NSCLC and how it regulated PDK4 to influence tumor aerobic glycolysis and mitochondrial function. METHOD: We examined the inhibitory effect of G-Rh2 on NSCLC through I proliferation assay, migration assay and flow cytometry in vitro. Subsequently, we verified the ability of G-Rh2 to inhibit tumor growth and metastasis by constructing subcutaneous tumor and metastasis models in nude mice. Proteomics analysis was conducted to analyze the action pathways of G-Rh2. Additionally, we assessed glycolysis and mitochondrial function using seahorse, PET-CT, Western blot, and RT-qPCR. RESULT: Treatment with G-Rh2 significantly inhibited tumor proliferation and migration ability both in vitro and in vivo. Furthermore, G-Rh2 inhibited the tumor's aerobic glycolytic capacity, including glucose uptake and lactate production, through the HIF1-α/PDK4 pathway. Overexpression of PDK4 demonstrated that G-Rh2 targeted the inhibition of PDK4 expression, thereby restoring mitochondrial function, promoting reactive oxygen species (ROS) accumulation, and inducing apoptosis. When combined with sodium dichloroacetate, a PDK inhibitor, it complemented the inhibitory capacity of PDKs, acting synergistically as a detoxifier. CONCLUSION: G-Rh2 could target and down-regulate the expression of HIF-1α, resulting in decreased expression of glycolytic enzymes and inhibition of aerobic glycolysis in tumors. Additionally, by directly targeting mitochondrial PDK, it elevated mitochondrial oxidative phosphorylation and enhanced ROS accumulation, thereby promoting tumor cells to undergo normal apoptotic processes.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Ginsenósidos , Subunidad alfa del Factor 1 Inducible por Hipoxia , Neoplasias Pulmonares , Fosforilación Oxidativa , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora , Ginsenósidos/farmacología , Ginsenósidos/uso terapéutico , Humanos , Animales , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/genética , Ratones , Línea Celular Tumoral , Piruvato Deshidrogenasa Quinasa Acetil-Transferidora/metabolismo , Fosforilación Oxidativa/efectos de los fármacos , Glucólisis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , Ratones Desnudos , Movimiento Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Transducción de Señal/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos
4.
Int Immunopharmacol ; 132: 111939, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38608471

RESUMEN

BACKGROUND: In this study, we investigated whether Exo regulate the proliferation and invasion of PC. METHODS: In this study, we isolated the Eriobotrya japonica Exo using Ultra-high speed centrifugal method. Mass spectrum were used for Exo active components analysis. PC (Capan-1 and Bxpc-3) cells proliferation, migration, and apoptosis were detected using CCK8, ethynyldeoxyuridine, transwell, wound healing, and flow cytometry analyses. We also constructed a lung metastatic mouse model and subcutaneous tumor model to illustrate the regulation effect of Exo or active components. Proteomics were used to reveal the regulatory mechanism responsible for the observed effects. RESULTS: We isolated Eriobotrya japonica Exo and found that Exo treatment significantly suppressed cell migration and proliferation in both in vivo and in vitro using Capan-1. Mass spectrum for Exo active components analysis found that Exo contains high amounts of corosolic acid (CRA). The further study found that CRA treatment inhibit the proliferation, migration, and increased cell death of both Capan-1 and Bxpc-3 cells in a concentration-dependent manner. In vivo experiments confirmed that CRA inhibited pulmonary metastasis by decreasing the number of metastatic foci. Cell proteomics analysis showed that CRA treatment induced spermidine/spermine N1-acetyltransferase 1 (SAT1)-dependent ferroptosis. Treatment with the ferroptosis suppressor ferrostatin-1 significantly reversed CRA-induced cell apoptosis. CONCLUSION: The data suggested that corosolic acid delivered by exosomes from Eriobotrya japonica decreased pancreatic cancer cell proliferation and invasion by inducing SAT1-mediated ferroptosis.


Asunto(s)
Acetiltransferasas , Proliferación Celular , Eriobotrya , Exosomas , Ferroptosis , Neoplasias Pulmonares , Neoplasias Pancreáticas , Animales , Ferroptosis/efectos de los fármacos , Neoplasias Pancreáticas/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Neoplasias Pancreáticas/metabolismo , Humanos , Proliferación Celular/efectos de los fármacos , Exosomas/metabolismo , Ratones , Línea Celular Tumoral , Acetiltransferasas/metabolismo , Acetiltransferasas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/secundario , Neoplasias Pulmonares/patología , Movimiento Celular/efectos de los fármacos , Triterpenos/farmacología , Triterpenos/uso terapéutico , Invasividad Neoplásica , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Desnudos , Ratones Endogámicos BALB C , Masculino , Apoptosis/efectos de los fármacos
5.
Chemosphere ; 355: 141828, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38552800

RESUMEN

Microorganisms play an important role in heavy metal bioremediation and soil fertility. The effects of soil inoculation with Pseudomonas sp. W112 on Cd accumulation in wheat were investigated by analyzing the transport, subcellular distribution and speciation of Cd in the soil and plants. Pseudomonas sp. W112 application significantly decreased Cd content in the roots, internode and grains by 10.2%, 29.5% and 33.0%, respectively, and decreased Cd transfer from the basal nodes to internodes by 63.5%. Treatment with strain W112 decreased the inorganic and water-soluble Cd content in the roots and increased the proportion of residual Cd in both the roots and basal nodes. At the subcellular level, the Cd content in the root cell wall and basal node cytosol increased by 19.6% and 61.8%, respectively, indicating that strain W112 improved the ability of the root cell wall and basal node cytosol to fix Cd. In the rhizosphere soil, strain W112 effectively colonized and significantly decreased the exchangeable Cd, carbonate-bound Cd and iron-manganese oxide-bound Cd content by 43.5%, 27.3% and 17.6%, respectively, while it increased the proportion of residual Cd by up to 65.2%. Moreover, a 3.1% and 23.5% increase in the pH and inorganic nitrogen content in the rhizosphere soil, respectively, was recorded. Similarly, soil bacterial community sequencing revealed that inoculating with strain W112 increased the abundance of Pseudomonas, Thauera and Azoarcus, which are associated with inorganic nitrogen metabolism, and decreased that of Acidobacteria, which is indicative of soil alkalinization. Hence, root application of Pseudomonas sp. W112 improved soil nitrogen availability and inhibited Cd accumulation in the wheat grains in a two-stage process: by reducing the Cd availability in the rhizosphere soil and by improving Cd interception and fixation in the wheat roots and basal nodes. Pseudomonas sp. W112 may be a suitable bioremediation agent for restoring Cd-contaminated wheat fields.


Asunto(s)
Cadmio , Contaminantes del Suelo , Cadmio/análisis , Triticum/metabolismo , Suelo/química , Disponibilidad Biológica , Pseudomonas/metabolismo , Contaminantes del Suelo/análisis , Raíces de Plantas/metabolismo , Nitrógeno/análisis
6.
Mol Med Rep ; 29(5)2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38516772

RESUMEN

Remifentanil­induced hyperalgesia (RIH) is characterized by the emergence of stimulation­induced pain, including phenomena such as allodynia and thermal hyperalgesia following remifentanil infusion. As a sequence­specific DNA binding transcription factor, PAX6 positively and negatively regulates transcription and is expressed in multiple cell types in the developing and adult central nervous system. It was hypothesized that puerarin could relieve RIH via targeting PAX6 to regulate transcription of transient receptor potential cation channel subfamily V Member 1 (TRPV1). A total of 32 rats were randomly divided into five groups, namely control group, RI group, RI + 10 mg/kg puerarin group (RI + puerarin10), RI + 20 mg/kg puerarin group (RI + puerarin20), and RI + 40 mg/kg puerarin group (RI + puerarin40). Mechanical and thermal hyperalgesia were tested at ­24, 2, 6, 24 and 48 h after remifentanil infusion. Following the sacrifice of rats after the last behavioral test, western blot was used to detect the expression levels of TRPV1 in the tissues; Immunofluorescence staining and western blotting were used to detect the expression of PAX6 in the spinal cord. PharmMapper and JASPAR were used to predict the binding sites of puerarin/PAX6/TRPV1. Chromatin immunoprecipitation­PCR and dual luciferase reporter assay were used to verify the targeting relationship between PAX6 and TRPV1. Immunofluorescence was used to detect the expression levels of TRPV1 and p­NR2B. The results revealed that puerarin (10, 20, 40 mg/kg) dose­dependently reduced thermal and mechanical hyperalgesia from 2 to 48 h after remifentanil infusion. Remifentanil infusion remarkably stimulated the expression of phosphorylated (p­)NR2B. Nevertheless, the increased amount of p­NR2B by RIH was dose­dependently suppressed by puerarin in rats. In conclusion, puerarin was revealed to attenuate postoperative RIH via targeting PAX6 to regulate the transcription of TRPV1.


Asunto(s)
Hiperalgesia , Isoflavonas , Animales , Ratas , Hiperalgesia/inducido químicamente , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/genética , Isoflavonas/farmacología , Isoflavonas/uso terapéutico , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/etiología , Piperidinas/farmacología , Ratas Sprague-Dawley , Remifentanilo/efectos adversos , Factor de Transcripción PAX6/efectos de los fármacos , Factor de Transcripción PAX6/metabolismo , Canales Catiónicos TRPV/efectos de los fármacos , Canales Catiónicos TRPV/genética , Canales Catiónicos TRPV/metabolismo
7.
Huan Jing Ke Xue ; 45(2): 1150-1160, 2024 Feb 08.
Artículo en Chino | MEDLINE | ID: mdl-38471952

RESUMEN

In order to evaluate the feasibility of using Burkholderia sp. Y4 as a cadmium (Cd)-reducing bacterial agent in contaminated wheat fields, the changes in the rhizosphere soil microbial community and Cd available state, as well as the content and transport characteristics of Cd in the wheat root, basal node, internode, and grain under the treatment of strain Y4 were tested using microbial high-throughput sequencing, step-by-step extraction, subcellular distribution, and occurrence analyses. The results showed that root application of strain Y4 significantly reduced the root and grain Cd content of wheat by 7.7% and 30.3%, respectively, compared with that in the control treatment. The Cd content and Cd transfer factor results in wheat vegetative organs showed that strain Y4 reduced the Cd transfer factor from basal node to internode by 79.3%, and Cd content in the wheat internode stem also decreased by 50.9%. The study of Cd occurrence morphology showed that strain Y4 treatment increased the proportion of residual Cd in roots and basal ganglia, decreased the contents of inorganic and water-soluble Cd in roots, and increased the content of residual Cd in basal ganglia. Further examination of the subcellular distribution of Cd showed that the Cd content in root cell walls and basal ganglia cell fluid increased by 21.3% and 98.2%, respectively, indicating that the Cd fixation ability of root cell walls and basal ganglia cell fluid was improved by the strain Y4 treatment. In the rhizosphere soil, it was found that the microbial community structure was changed by strain Y4 application. Under the Y4 treatment, the relative abundance of Burkholderia increased from 9.6% to 11.5%, whereas that of Acidobacteriota decreased. Additionally, the relative abundance of Gemmatimonadales, Pseudomonadales, and Chitinophagales were also increased by strain Y4 treatment. At the same time, the application of strain Y4 increased the pH value of rhizosphere soil by 8.3%. The contents of exchangeable Cd, carbonate-bound Cd, and iron-manganese oxide-bound Cd in the soil decreased by 44.4%, 21.7%, and 15.9%, respectively, whereas the proportion of residual Cd reached 53.6%. Root application of strain Y4 increased the contents of nitrate nitrogen and ammonium nitrogen in the soil by 22.0% and 21.4%, respectively, and the contents of alkaline nitrogen also increased to a certain extent. In conclusion, the root application of strain Y4 not only improved soil nitrogen availability but also inhibited Cd transport and accumulation from contaminated soil to wheat grains in a "two-stage" manner by reducing Cd availability in rhizosphere soil and improving Cd interception and fixation capacity of wheat roots and basal nodes. Therefore, Burkholderia Y4 has application potential as a Cd-reducing and growth-promoting agent in wheat.


Asunto(s)
Burkholderia , Compuestos Férricos , Contaminantes del Suelo , Cadmio/análisis , Triticum , Burkholderia/fisiología , Factor de Transferencia , Suelo/química , Nitrógeno/análisis , Contaminantes del Suelo/análisis
8.
Cell Mol Biol Lett ; 29(1): 43, 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38539084

RESUMEN

BACKGROUND: Circular RNAs (circRNAs) are single-stranded RNAs with covalently closed structures that have been implicated in cancer progression. However, the regulatory mechanisms remain largely unclear. So, the aim of this study was to reveal the role and regulatory mechanisms of circ-SLC16A1. METHODS: In this study, next-generation sequencing was used to identify abnormally expressed circRNAs between cancerous and para-carcinoma tissues. Fluorescence in situ hybridization and quantitative reverse transcription polymerase chain reaction were performed to assess the expression patterns of circ-solute carrier family 16 member 1 (SLC16A1) in non-small cell lung cancer (NSCLC) cells and tissue specimens. The dual-luciferase reporter assay was utilized to identify downstream targets of circ-SLC16A1. Transwell migration, wound healing, 5-ethynyl-2'-deoxyuridine incorporation, cell counting, and colony formation assays were conducted to assess the proliferation and migration of NSCLC cells. A mouse tumor xenograft model was employed to determine the roles of circ-SLC16A1 in NSCLC progression and metastasis in vivo. RESULTS: The results found that circ-SLC16A1 was upregulated in NSCLC cells and tissues. Downregulation of circ-SLC16A1 inhibited tumor growth by reducing proliferation, lung metastasis, and lymphatic metastasis of NSCLC cells, and arrested the cell cycle in the G1 phase. Also, silencing of circ-SLC16A1 promoted apoptosis of NSCLC cells. The results of bioinformatics analysis and the dual-luciferase reporter assay confirmed that microRNA (miR)-1287-5p and profilin 2 (PFN2) are downstream targets of circ-SLC16A1. PFN2 overexpression or circ-SLC16A1 inhibition restored proliferation and migration of NSCLC cells after silencing of circ-SLC16A1. PFN2 overexpression restored migration and proliferation of NSCLC cells post miR-1287-5p overexpression. CONCLUSIONS: Collectively, these findings show that miR-1287-5p/PFN2 signaling was associated with downregulation of circ-SLC16A1 and reduced invasion and proliferation of NSCLC cells. So, circ-SLC16A1 is identified as a mediator of multiple pro-oncogenic signaling pathways in NSCLC and can be targeted to suppress tumor progression.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , Animales , Humanos , Ratones , Carcinoma de Pulmón de Células no Pequeñas/genética , Línea Celular Tumoral , Proliferación Celular/genética , Modelos Animales de Enfermedad , Hibridación Fluorescente in Situ , Luciferasas , Neoplasias Pulmonares/genética , MicroARNs/genética , Profilinas , ARN Circular/genética
9.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(1): 73-77, 2024 Jan.
Artículo en Chino | MEDLINE | ID: mdl-38404276

RESUMEN

OBJECTIVE: To analyze the predictive value of von Willebrand factor (vWF) for venous thromboembolism (VTE) of patients in intensive care unit (ICU) by using propensity score matching (PSM). METHODS: Patients admitted to ICU of the Second Affiliated Hospital of Kunming Medical University from December 2020 to June 2022 who stayed in ICU for ≥72 hours and underwent daily bedside vascular ultrasound screening were included. Baseline data such as age, gender, primary disease, and chronic comorbidities were collected. Coagulation indexes before admission to ICU and 24 hours and 48 hours after ICU admission were collected, including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), international normalized ratio (INR), fibrinogen (Fib), fibrin monomer (FM), vWF, D-dimer, antithrombin III (ATIII), etc. Patients were divided into VTE group and non-VTE group according to whether they had VTE or not [diagnosis of VTE: patients underwent daily ultrasound screening of bedside blood vessels (both upper and lower limbs, visceral veins), and those suspected of having thrombosis were confirmed by ultrasonographer or pulmonary angiography]. Using PSM analysis method, the VTE group was used as the benchmark to conduct 1 : 1 matching of age, whether there was malignant tumor, whether there was infection, whether there was diabetes, and coagulation indicators before admission to ICU. Finally, the cases with balanced covariates between the two groups were obtained. The risk factors of VTE were analyzed by multivariate Logistic regression analysis. Receiver operator characteristic curve (ROC curve) was drawn to evaluate the predictive value of vWF in the occurrence of VTE in critically ill patients. RESULTS: A total of 120 patients were enrolled, of which 18 (15.0%) were diagnosed with VTE within 72 hours after admission to ICU, and 102 (85.0%) were not found to have thrombus in ICU. Before PSM, there were significant differences in age, gender, proportion of malignant tumor and infection, and coagulation indexes between VTE group and non-VTE group. After PSM, 14 pairs were successfully matched, and the unbalanced covariables between the two groups reached equilibrium. Multivariate Logistic regression analysis showed that vWF was an independent risk factor for VTE at 48 hours after ICU admission in critically ill patients [odds ratio (OR) = 1.165, 95% confidence interval (95%CI) was 1.000-1.025, P = 0.004]. ROC curve analysis showed that the area under the ROC curve (AUC) of vWF at 48 hours after ICU admission for predicting VTE was 0.782, 95%CI was 0.618-0.945, P = 0.007. When the optimal cut-off value was 312.12%, the sensitivity was 67.7% and the specificity was 93.0. CONCLUSIONS: Dynamic monitoring of vWF is helpful to predict the occurrence of VTE in ICU patients, and vWF at 48 hours after ICU admission has certain value in predicting the occurrence of VTE.


Asunto(s)
Neoplasias , Tromboembolia Venosa , Humanos , Factor de von Willebrand , Tromboembolia Venosa/diagnóstico , Pronóstico , Estudios Retrospectivos , Enfermedad Crítica/epidemiología , Puntaje de Propensión , Unidades de Cuidados Intensivos , Curva ROC
10.
Plants (Basel) ; 13(3)2024 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-38337913

RESUMEN

An in-depth understanding of Se uptake and metabolism in plants is necessary for developing Se biofortification strategies. Thus, hydroponic experiments were conducted to investigate the associated processes and mechanisms of organic Se (selenomethionine (SeMet) and selenomethionine-oxide (SeOMet)) uptake, translocation, transformation and their interaction in wheat, in comparison to inorganic Se. The results showed that Se uptake by the roots and the root-to-shoot translocation factor under the SeMet treatment were higher than those under the selenite, selenate and SeOMet treatments. The uptake and translocation of SeMet were higher than those of SeOMet within 72 h, although the differences gradually narrowed with time. The uptake of SeMet and SeOMet was also sensitive to the aquaporin inhibitor: AgNO3 addition resulted in 99.5% and 99.9% inhibitions of Se in the root in the SeMet and SeOMet treatments, respectively. Once absorbed by the root, they rapidly assimilated to other Se forms, and SeMet and Se-methyl-selenocysteine (MeSeCys) were the dominant species in SeMet- and SeOMet-treated plants, while notably, an unidentified Se form was also found in the root and xylem sap under the SeMet treatment. In addition, within 16 h, SeOMet inhibited the uptake and translocation of SeMet, while the inhibition was weakened with longer treatment time. Taken together, the present study provides new insights for the uptake and transformation processes of organic Se within plants.

11.
ACS Appl Bio Mater ; 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38382060

RESUMEN

Recently, there has been significant interest in nanoscale metal-organic frameworks (NMOFs) characterized by ordered crystal structures and nanoscale coordination polymers (NCPs) featuring amorphous structures. These structures arise from the coordination interactions between inorganic metal ions or clusters and organic ligands. Their advantages, such as the ability to tailor composition and structure, efficiently encapsulate diverse therapeutic or imaging agents within porous frameworks, inherent biodegradability, and surface functionalization capability, position them as promising carriers in the biomedical fields. This review provides an overview of the synthesis and surface modification strategies employed for NMOFs and NCPs, along with their applications in cancer treatment and biological imaging. Finally, future directions and challenges associated with the utilization of NMOFs and NCPs in cancer treatment and diagnosis are also discussed.

12.
Sci Adv ; 10(6): eadk0716, 2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38324678

RESUMEN

Nanoparticle-based cancer immunotherapy has shown promising therapeutic potential in clinical settings. However, current research mainly uses nanoparticles as delivery vehicles but overlooks their potential to directly modulate immune responses. Inspired by the endogenous endoplasmic reticulum (ER) stress caused by unfolded/misfolded proteins, we present a rationally designed immunogenic cell death (ICD) inducer named NanoICD, which is a nanoparticle engineered for ER targeting and retention. By carefully controlling surface composition and properties, we have obtained NanoICD that can effectively accumulate in the ER, induce ER stress, and activate ICD-associated immune responses. In addition, NanoICD is generally applicable to various proteins and enzymes to further enhance the immunomodulatory capacity, exemplified by encapsulating catalase (CAT) to obtain NanoICD/CAT, effectively alleviated immunosuppressive tumor microenvironment and induced robust antitumor immune responses in 4T1-bearing mice. This work demonstrates engineered nanostructures' potential to autonomously regulate biological processes and provides insights into the development of advanced nanomedicines for cancer treatment.


Asunto(s)
Antineoplásicos , Nanopartículas , Neoplasias , Ratones , Animales , Neoplasias/tratamiento farmacológico , Muerte Celular Inmunogénica , Antineoplásicos/farmacología , Inmunoterapia , Nanopartículas/uso terapéutico , Línea Celular Tumoral , Microambiente Tumoral
13.
Angew Chem Int Ed Engl ; 63(8): e202318533, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38196066

RESUMEN

Photochemical regulation provides precise control over enzyme activities with high spatiotemporal resolution. A promising approach involves anchoring "photoswitches" at enzyme active sites to modulate substrate recognition. However, current methods often require genetic mutations and irreversible enzyme modifications for the site-specific anchoring of "photoswitches", potentially compromising the enzyme activities. Herein, we present a pioneering reversible nano-inhibitor based on molecular imprinting technique for bidirectional regulation of intracellular enzyme activity. The nano-inhibitor employs a molecularly imprinted polymer nanoparticle as its body and azobenzene-modified inhibitors ("photoswitches") as the arms. By using a target enzyme as the molecular template, the nano-inhibitor acquires oriented binding sites on its surface, resulting in a high affinity for the target enzyme and non-covalently firm anchoring of the azobenzene-modified inhibitor to the enzyme active site. Harnessing the reversible isomerization of azobenzene units upon exposure to ultraviolet and visible light, the nano-inhibitor achieves bidirectional enzyme activity regulation by precisely docking and undocking inhibitor at the active site. Notably, this innovative approach enables the facile in situ regulation of intracellular endogenous enzymes, such as carbonic anhydrase. Our results represent a practical and versatile tool for precise enzyme activity regulation in complex intracellular environments.


Asunto(s)
Luz , Impresión Molecular , Compuestos Azo/farmacología , Compuestos Azo/química , Impresión Molecular/métodos , Sitios de Unión
14.
J Agric Food Chem ; 72(3): 1768-1778, 2024 Jan 24.
Artículo en Inglés | MEDLINE | ID: mdl-38217861

RESUMEN

To reduce the health risks of exposure to Cd and Pb in wheat, a field experiment was conducted to investigate the differences in Cd and Pb bioaccessibility among the grains of 11 wheat cultivars and their relationships with the nutrient compositions of grains. The grain concentrations (Cd: 0.14-0.56 mg kg-1, Pb: 0.08-0.39 mg kg-1) and bioaccessibility (5.28-57.43% and 0.72-7.72% for Cd and Pb in the intestinal phase, respectively) of Cd and Pb differed significantly among the 11 cultivars. A safe wheat cultivar (Shannong16) with a relatively low health risk and the lowest grain Cd and Pb concentrations was selected. Ca, Mg, phytate, and methionine played key roles in affecting Cd and Pb bioaccessibility in wheat, with Ca and phytate significantly negatively correlated with Cd and Pb bioaccessibility. These findings can be used to optimize the selection strategy for safe wheat cultivars for healthy grain production in Cd-polluted farmland.


Asunto(s)
Cadmio , Contaminantes del Suelo , Cadmio/análisis , Triticum , Plomo , Ácido Fítico , Contaminantes del Suelo/análisis , Nutrientes , Grano Comestible/química , Suelo
15.
Artículo en Inglés | MEDLINE | ID: mdl-37853634

RESUMEN

Copper sulfide based phototherapy, including photothermal therapy and photodynamic therapy, is an emerging minimally invasive treatment of tumor, which the light was converted to heat or reactive oxygen to kill the tumor cells. Compared with conventional chemotherapy and radiation therapy, Cu2-x S based phototherapy is more efficient and has fewer side effects. However, considering the dose-dependent toxicity of Cu2-x S, the performance of Cu2-x S based phototherapy still cannot meet the requirement of the clinical application to now. To overcome this limitation, engineering of Cu2-x S to improve the phototherapy performance by increasing light absorption has attracted extensive attention. For better guidance of Cu2-x S engineering, we outline the currently engineering method being explored, including (1) structural engineering, (2) compositional engineering, (3) functional engineering, and (4) performance engineering. Also, the relationship between the engineering method and phototherapy performance was discussed in this review. In addition, the further development of Cu2-x S based phototherapy is prospected, including smart materials based phototherapy, phototherapy induced immune microenvironment modulation et al. This review will provide new ideas and opportunities for engineering of Cu2-x S with better phototherapy performance. This article is categorized under: Diagnostic Tools > In Vivo Nanodiagnostics and Imaging Therapeutic Approaches and Drug Discovery > Nanomedicine for Oncologic Disease.


Asunto(s)
Nanopartículas , Neoplasias , Fotoquimioterapia , Humanos , Cobre/química , Cobre/farmacología , Fototerapia/métodos , Sulfuros/química , Sulfuros/farmacología , Neoplasias/terapia , Nanopartículas/química , Microambiente Tumoral
16.
J Hazard Mater ; 463: 132890, 2024 02 05.
Artículo en Inglés | MEDLINE | ID: mdl-37922582

RESUMEN

Large areas of crop yields in northern China have faced with cadmium (Cd) contamination problems. Mercapto-modified palygorskite (MP), as a highly efficient immobilization material, could reduce Cd absorption in wheat and alleviate its biotoxicity. However, the molecular mechanism underlying MP-mediated Cd reduction and detoxification processes in wheat is not well understood. This aim of this study was to investigate the biochemical and molecular mechanisms underlying the reduction in Cd accumulation in wheat (Triticum aestivum L.). The results showed that MP application decreased the Cd concentration by 68.91-74.32% (root) and 70.68-77.2% (shoot), and significantly increased the glutathione (GSH) and phytochelatins (PCs) contents in root and shoot. In addition, with the application of MP, the percentage of Cd in the cell walls and organelles of wheat decreased, while that of Cd in soluble components was increased. The content of Cd in all components was significantly reduced. Ultrastructural analysis revealed that MP thickened the cell wall, promoted vesicle formation in the membrane and protected the integrity of intracellular organelles in wheat. Transcriptome analysis further confirmed the above results. MP upregulated the expression of several genes (CCR, CAD COMT and SUS) involved in cell wall component biosynthesis and promoted vesicle formation on cell membranes by upregulating the expression of PLC and IPMK genes. In addition, genes related to antioxidant synthesis (PGD, glnA and GSS) and photosynthesis (Lhca, Lhcb) were altered by MP to alleviate Cd toxicity in wheat. This present work will help to more thoroughly elucidate the molecular mechanism by which wheat defends against Cd contamination under MP application and provide and important research basis for the application of this material in the future.


Asunto(s)
Cadmio , Contaminantes del Suelo , Cadmio/metabolismo , Triticum/genética , Triticum/metabolismo , Transcriptoma , Compuestos de Silicona , Glutatión/metabolismo , Contaminantes del Suelo/metabolismo
17.
Heliyon ; 9(12): e22177, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38046157

RESUMEN

Background: We studied AKI incidence and prognosis in cardiac surgery patients under and over 60 years old. Methods: We studied AKI in patients who underwent cardiac surgery at the First Affiliated Hospital of Wenzhou Medical University between Jan 2020 and Dec 2021, using improved global prognostic criteria for diagnosis. Results: After analyzing 781 patients (402 males, 379 females), AKI incidence after surgery was 30.22 %. Adjusting for propensity scores revealed no significant difference in AKI incidence between young males (24.1 %) and females (19.3 %). However, young females had higher AKI stages. Among older patients, AKI incidence was comparable between males (43.4 %) and females (42.2 %), but females had longer intubation times. Independent risk factors for AKI included age, male gender, and BMI, while intraoperative hemoglobin level was protective. Conclusions: No gender gap in AKI frequency for <60 years old and ≥60 years old post-cardiac surgery, yet women display increased AKI severity and extended intubation duration.

18.
Front Endocrinol (Lausanne) ; 14: 1286900, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38089611

RESUMEN

Stem cells have self-renewal, replication, and multidirectional differentiation potential, while progenitor cells are undifferentiated, pluripotent or specialized stem cells. Stem/progenitor cells secrete various factors, such as cytokines, exosomes, non-coding RNAs, and proteins, and have a wide range of applications in regenerative medicine. However, therapies based on stem cells and their secreted exosomes present limitations, such as insufficient source materials, mature differentiation, and low transplantation success rates, and methods addressing these problems are urgently required. Ultrasound is gaining increasing attention as an emerging technology. Low-intensity pulsed ultrasound (LIPUS) has mechanical, thermal, and cavitation effects and produces vibrational stimuli that can lead to a series of biochemical changes in organs, tissues, and cells, such as the release of extracellular bodies, cytokines, and other signals. These changes can alter the cellular microenvironment and affect biological behaviors, such as cell differentiation and proliferation. Here, we discuss the effects of LIPUS on the biological functions of stem/progenitor cells, exosomes, and non-coding RNAs, alterations involved in related pathways, various emerging applications, and future perspectives. We review the roles and mechanisms of LIPUS in stem/progenitor cells and exosomes with the aim of providing a deeper understanding of LIPUS and promoting research and development in this field.


Asunto(s)
Exosomas , Exosomas/metabolismo , Células Madre , Ondas Ultrasónicas , Diferenciación Celular/fisiología , Citocinas/metabolismo
19.
Int J Impot Res ; 2023 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-38052978

RESUMEN

Male hypogonadism can seriously affect male health and fertility, yet comprehensive bibliometric and visualization analyses of research in this area have been lacking. This study aimed to examine the distribution of literature, identify research hotspots, and discern development trends in male hypogonadism by analyzing 4026 English documents published between 2000 and 2023 using bibliometric and visual analyses. The results indicated a significant increase in publications and citations related to male hypogonadism over the past two decades, with the United States, the University of Florence, Maggi M, and the Journal of Clinical Endocrinology & Metabolism recognized as the most productive and highly cited country, institution, author, and journal, respectively. The article titled "The GPR54 gene as a regulator of puberty" received the highest number of citations. The keywords were categorized into four distinct clusters, including the etiology and pathogenesis of male hypogonadism, symptoms of late-onset hypogonadism, testosterone replacement therapy and its contraindications, the correlation between male hypogonadism and metabolic syndrome (MetS), obesity, and the epidemiology of male hypogonadism. The most frequently co-occurring keywords were "hypogonadism", "testosterone", and "men", while "oxidative stress" was the most prominent burst keyword. The analysis also identified "male infertility" and "oxidative stress" as the primary burst keywords in the last five years, indicating their emerging high-interest topics. Overall, this study provides a comprehensive overview of male hypogonadism research, offering valuable insights for researchers interested in this area, including potential collaborators, current research hotspots, and future research directions.

20.
J Neuroinflammation ; 20(1): 284, 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38037161

RESUMEN

BACKGROUND: Neuroinflammation mediated by microglial pyroptosis is an important pathogenic mechanism of septic encephalopathy (SAE). It has been reported that TRIM45 is associated with tumours and inflammatory diseases. However, the role of TRIM45 in SAE and the relationship between TRIM45 and microglial pyroptosis are unknown. In this study, we found that TRIM45 played an important role in regulating microglial pyroptosis and the molecular mechanism. METHODS: SAE was induced by intraperitoneal injection of LPS in WT and AAV-shTRIM45 mice. BV2 cells were treated with LPS/ATP in vitro. Cognitive function was assessed by the Morris water maze. Nissl staining was used to evaluate histological and structural lesions. ELISA was used to dectect neuroinflammation. qPCR was used to detect the mRNA levels of inflammatory cytokines, NLRP3, and autophagy genes. Western blotting and immunofluorescence analysis were used to analyse the expression of the proteins. Changes in reactive oxygen species (ROS) in cells were observed by flow cytometry. Changes in mitochondrial membrane potential in BV2 cells were detected by JC-1 staining. Peripheral blood mononuclear cells were extracted from blood by density gradient centrifugation and then used for qPCR, western blotting and flow detection. To further explore the mechanism, we used the overexpression plasmids TRIM45 and Atg5 as well as siRNA-TRIM45 and siRNA-Atg5 to analyse the downstream pathway of NLRP3. The protein and mRNA levels of TRIM45 in peripheral blood mononuclear cells from sepsis patients were examined. RESULTS: Knocking down TRIM45 protected against neuronal damage and cognitive impairment in septic mice. TRIM45 knockdown inhibited microglial pyroptosis and the secretion of inflammatory cytokines in vivo and in vitro, which was mediated by NLRP3/Gsdmd-N activation. Overexpression of TRIM45 could activate NLRP3 and downstream proteins. Further examination showed that TRIM45 regulated the activation of NLRP3 by altering Atg5 and regulating autophagic flux. It was also found that overexpression and knockdown of TRIM45 affected the changes in ROS and mitochondrial membrane potential. Thus, knocking down TRIM45 could reduce microglial pyroptosis, the secretion of proinflammatory cytokines, and neuronal damage and improve cognitive function. In addition, the level of TRIM45 protein in septic patients was increased. There was a positive linear correlation between APACHE II score and TRIM45, between SOFA score and TRIM45. Compared to group GCS > 9, level of TRIM45 were increased in group GCS ≤ 8. CONCLUSION: TRIM45 plays a key role in neuroinflammation caused by LPS, and the mechanism may involve TRIM45-mediated exacerbation of microglial pyroptosis via the Atg5/NLRP3 axis.


Asunto(s)
Piroptosis , Encefalopatía Asociada a la Sepsis , Animales , Humanos , Ratones , Citocinas/genética , Inflamasomas , Leucocitos Mononucleares , Lipopolisacáridos , Microglía , Enfermedades Neuroinflamatorias , Proteína con Dominio Pirina 3 de la Familia NLR/genética , Especies Reactivas de Oxígeno , Proteínas Represoras , ARN Mensajero , ARN Interferente Pequeño
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