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1.
Int Immunopharmacol ; 132: 111939, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38608471

RESUMO

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.

2.
Cell Mol Biol Lett ; 29(1): 43, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38539084

RESUMO

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.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Animais , Humanos , Camundongos , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Modelos Animais de Doenças , Hibridização in Situ Fluorescente , Luciferases , Neoplasias Pulmonares/genética , MicroRNAs/genética , Profilinas , RNA Circular/genética
3.
Mol Med Rep ; 29(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38516772

RESUMO

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.


Assuntos
Hiperalgesia , Isoflavonas , Animais , Ratos , Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Hiperalgesia/genética , Isoflavonas/farmacologia , Isoflavonas/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Dor Pós-Operatória/etiologia , Piperidinas/farmacologia , Ratos Sprague-Dawley , Remifentanil/efeitos adversos , Fator de Transcrição PAX6/efeitos dos fármacos , Fator de Transcrição PAX6/metabolismo , Canais de Cátion TRPV/efeitos dos fármacos , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismo
4.
Chemosphere ; 355: 141828, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38552800

RESUMO

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.


Assuntos
Cádmio , Poluentes do Solo , Cádmio/análise , Triticum/metabolismo , Solo/química , Disponibilidade Biológica , Pseudomonas/metabolismo , Poluentes do Solo/análise , Raízes de Plantas/metabolismo , Nitrogênio/análise
5.
Huan Jing Ke Xue ; 45(2): 1150-1160, 2024 Feb 08.
Artigo em Chinês | MEDLINE | ID: mdl-38471952

RESUMO

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.


Assuntos
Burkholderia , Compostos Férricos , Poluentes do Solo , Cádmio/análise , Triticum , Burkholderia/fisiologia , Fator de Transferência , Solo/química , Nitrogênio/análise , Poluentes do Solo/análise
6.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 36(1): 73-77, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38404276

RESUMO

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.


Assuntos
Neoplasias , Tromboembolia Venosa , Humanos , Fator de von Willebrand , Tromboembolia Venosa/diagnóstico , Prognóstico , Estudos Retrospectivos , Estado Terminal/epidemiologia , Pontuação de Propensão , Unidades de Terapia Intensiva , Curva ROC
7.
Sci Adv ; 10(6): eadk0716, 2024 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-38324678

RESUMO

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.


Assuntos
Antineoplásicos , Nanopartículas , Neoplasias , Camundongos , Animais , Neoplasias/tratamento farmacológico , Morte Celular Imunogênica , Antineoplásicos/farmacologia , Imunoterapia , Nanopartículas/uso terapêutico , Linhagem Celular Tumoral , Microambiente Tumoral
8.
Plants (Basel) ; 13(3)2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38337913

RESUMO

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.

9.
ACS Appl Bio Mater ; 2024 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-38382060

RESUMO

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.

10.
Angew Chem Int Ed Engl ; 63(8): e202318533, 2024 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-38196066

RESUMO

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.


Assuntos
Luz , Impressão Molecular , Compostos Azo/farmacologia , Compostos Azo/química , Impressão Molecular/métodos , Sítios de Ligação
11.
J Agric Food Chem ; 72(3): 1768-1778, 2024 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-38217861

RESUMO

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.


Assuntos
Cádmio , Poluentes do Solo , Cádmio/análise , Triticum , Chumbo , Ácido Fítico , Poluentes do Solo/análise , Nutrientes , Grão Comestível/química , Solo
12.
J Hazard Mater ; 463: 132890, 2024 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-37922582

RESUMO

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.


Assuntos
Cádmio , Poluentes do Solo , Cádmio/metabolismo , Triticum/genética , Triticum/metabolismo , Transcriptoma , Compostos de Silício , Glutationa/metabolismo , Poluentes do Solo/metabolismo
13.
Int J Impot Res ; 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-38052978

RESUMO

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.

14.
J Neuroinflammation ; 20(1): 284, 2023 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-38037161

RESUMO

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.


Assuntos
Piroptose , Encefalopatia Associada a Sepse , Animais , Humanos , Camundongos , Citocinas/genética , Inflamassomos , Leucócitos Mononucleares , Lipopolissacarídeos , Microglia , Doenças Neuroinflamatórias , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Espécies Reativas de Oxigênio , Proteínas Repressoras , RNA Mensageiro , RNA Interferente Pequeno
15.
Heliyon ; 9(12): e22177, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38046157

RESUMO

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.

16.
Front Endocrinol (Lausanne) ; 14: 1286900, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38089611

RESUMO

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.


Assuntos
Exossomos , Exossomos/metabolismo , Células-Tronco , Ondas Ultrassônicas , Diferenciação Celular/fisiologia , Citocinas/metabolismo
17.
Artigo em Inglês | MEDLINE | ID: mdl-37853634

RESUMO

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.

18.
Plant Physiol Biochem ; 204: 108108, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37864926

RESUMO

Selenium (Se) fertilizer has been recently used to reduce cadmium (Cd) accumulation in plant. A pot culture was performed to analyze Cd uptake, translocation, and distribution in wheat plants during the reproductive growth period in a Cd-contaminated soil after selenate was applied to the soil, and a hydroponic culture was carried out to investigate the effects of selenate application on Cd2+ influx, subcellular Cd distribution, and Cd accumulation in wheat seedlings. Results showed that selenate application had no significant effect on DTPA-Cd and Cd fraction in soil. The application of selenate greatly inhibited the whole-plant Cd absorption by 14%-23%. In addition, selenate prompted the retention of Cd in root by increasing the Cd distribution in the vacuole, which reduced the root-to-shoot Cd translocation by 18%-53%. The application of selenate increased the Cd concentration in nodes, inhibited Cd remobilization from nutritive organs to grain, and ultimately reduced Cd accumulation in wheat grain. Further, heading to grain filling was the key growth stage for exogenous selenate to regulate grain Cd accumulation. In summary, soil selenate application is an effective method to reduce grain Cd concentration in wheat, which provided scientific basis for remediation of Cd-contaminated soil.


Assuntos
Selênio , Poluentes do Solo , Ácido Selênico/farmacologia , Cádmio/análise , Triticum , Selênio/farmacologia , Solo , Grão Comestível/química
19.
Ecotoxicol Environ Saf ; 266: 115559, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37820475

RESUMO

Cadmium (Cd) contamination in wheat fields has become a major environmental issue in many regions of the world. Mercapto-palygorskite (MPAL) is a high-performance amendment that can effectively immobilize Cd in alkaline wheat soil. However, MAPL as an in-situ Cd immobilization strategy for alkaline wheat soil remains to be evaluated on a field-scale and the underlying mechanisms requires further evaluation. Here, MPAL were used as soil amendment to evaluate their immobilization efficiency on Cd-contaminated alkaline soil in the field experiments. The field experiments showed that MPAL application significantly reduced wheat grain Cd concentration from 0.183 mg/kg to 0.056 mg/kg, with Cd concentration in wheat grain treated with MPAL all falling below the limit value of 0.1 mg/kg as defined in China's food safety standard (GB 2762-2022). The maximal immobilization efficiency of MPAL on soil Cd figured out by diethylenetriaminepentaacetic acid (DTPA) extraction was 61.5%. The mechanisms involved in Cd immobilization by MPAL were mainly related to the enhanced sorption of Cd onto Fe oxides, and the removal of amorphous or free Fe oxides from soil had a substantial impact on Cd immobilization efficiency by MPAL. Furthermore, the antagonistic effect between Mn and Cd uptake may also contribute to the reduction of wheat Cd accumulation after MPAL application. The current research can provide theoretical and technical support for the large-scale application of MPAL in Cd-contaminated wheat fields.


Assuntos
Poluentes do Solo , Solo , Cádmio/análise , Triticum , Poluentes do Solo/análise , Óxidos
20.
Huan Jing Ke Xue ; 44(9): 5204-5213, 2023 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-37699838

RESUMO

To investigate the effects of nano-copper oxide (CuO NPs) on plant growth, physio-biochemical characteristics, and heavy metal content under cadmium stress, a hydroponics experiment was conducted on the effects of single and combined treatments of CuO NPs (0, 10, 20, and 50 mg·L-1) and Cd (0, 1, and 5 µmol·L-1) on the fresh weight, photosynthetic pigment content, MDA content, antioxidant enzyme activity (CAT, POD, SOD, and GR), and Cu and Cd contents in Brassica chinensis L. The results showed that under the single addition of CuO NPs, the fresh weight and activities of CAT, POD, and GR were inhibited as a whole. Photosynthetic pigment content and SOD activity increased first and then decreased with the increase in CuO NPs concentration, whereas MDA content in leaves and roots, and Cu content in subcells of B. chinensis L. increased with the increasing of CuO NPs. As compared with that in the control, CuO NPs promoted the growth of B. chinensis L., and the fresh weight increased by 8.70%-44.87% at 1 µmol·L-1 Cd. When the content of Cd was up to 5 µmol·L-1, a low content (10 mg·L-1) of CuO NPs promoted the growth of B. chinensis L., whereas a high concentration (50 mg·L-1) showed an inhibitory effect. The addition of CuO NPs could increase photosynthetic pigment and MDA contents under different Cd stress, and MDA content in leaves and roots of B. chinensis L. increased by 4.34%-36.27% and 13.43%-131.04%, respectively, than that in the control groups. Under the same concentration of 1 µmol·L-1 Cd, the addition of CuO NPs decreased the activities of CAT and GR, whereas the activity of POD increased. When the content of Cd was up to 5 µmol·L-1, CuO NPs increased the POD activity and inhibited the activity of SOD and GR. The activities of CAT and CAT in the leaves of B. chinensis L. initially showed an increasing and then decreasing trend. CuO NPs and Cd showed antagonistic effects, the maximum reduction of Cd content in leaves and roots of Brassica chinensis L. under 1 µmol·L-1 Cd treatment was 45.64% and 33.39%, and that under 5 µmol·L-1 Cd treatment was 18.25% and 25.35%, respectively. The content of Cu and Cd in subcellular organs of the plants decreased, but the proportion of soluble components increased. These results indicated that CuO NPs at low concentrations promoted plant growth under Cd stress and further inhibited the absorption of Cd but increased the oxidative damage to B. chinensis L.


Assuntos
Brassica , Metais Pesados , Cobre , Cádmio/toxicidade , Metais Pesados/toxicidade , Antioxidantes , Óxidos , Superóxido Dismutase
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