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1.
Ecotoxicol Environ Saf ; 279: 116453, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38772139

ABSTRACT

Chlorinated polyfluorinated ether sulfonate, commercially known as F-53B, has been associated with adverse birth outcomes. However, the reproductive toxicology of F-53B on the placenta remains poorly understood. To address this gap, we examined the impact of F-53B on placental injury and its underlying molecular mechanisms in vivo. Pregnant C57BL/6 J female mice were randomly allocated to three groups: the control group, F-53B 0.8 µg/kg/day group, and F-53B 8 µg/kg/day group. After F-53B exposure through free drinking water from gestational day (GD) 0.5-14.5, the F-53B 8 µg/kg/day group exhibited significant increases in placental weights and distinctive histopathological alterations, including inflammatory cell infiltration, heightened syncytiotrophoblast knots, and a loosened trophoblastic basement membrane. Within the F-53B 8 µg/kg/day group, placental tissue exhibited increased apoptosis, as indicated by increased caspase3 activation. Furthermore, F-53B potentially induced the NF-κB signaling pathway activation through IκB-α phosphorylation. Subsequently, this activation upregulated the expression of inflammatory cytokines and components of the NLRP3 inflammasome, including activated caspase1, IL-1ß, IL-18, and cleaved gasdermin D (GSDMD), ultimately leading to pyroptosis in the mouse placenta. Our findings reveal a pronounced inflammatory injury in the placenta due to F-53B exposure, suggesting potential reproductive toxicity at concentrations relevant to the human population. Further toxicological and epidemiological investigations are warranted to conclusively assess the reproductive health risks posed by F-53B.

2.
Environ Toxicol Pharmacol ; : 104468, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38759849

ABSTRACT

Chlorpyrifos, widely used for pest control, is known to have various harmful effects, although its toxic effects in macrophages and the mechanisms underlying its toxicity remain unclear. The present study investigated the toxic effects of chlorypyrifos in a macrophage cell line. Here, we found that chlorpyrifos induced cytotoxicity and genotoxicity in RAW264.7 macrophages. Moreover, chlorpyrifos induced intracellular ROS production, subsequently leading to lipid peroxidation. Chlorpyrifos reduced the activation of antioxidative enzymes including superoxide dismutase, catalase, and glutathione peroxidase. Chlorpyrifos upregulated HO-1 expression and activated the Keap1-Nrf2 pathway, as indicated by enhanced Nrf2 phosphorylation and Keap1 degradation. Chlorpyrifos exerted effects on the following in a dose-dependent manner: cytotoxicity, genotoxicity, lipid peroxidation, intracellular ROS production, antioxidative enzyme activity reduction, HO-1 expression, Nrf2 phosphorylation, and Keap1 degradation. Notably, N-acetyl-L-cysteine successfully inhibited chlorpyrifos-induced intracellular ROS generation, cytotoxicity, and genotoxicity. Thus, chlorpyrifos may induce cytotoxicity and genotoxicity by promoting intracellular ROS production and suppressing the antioxidative defense system activation in macrophages.

3.
Huan Jing Ke Xue ; 45(5): 2817-2827, 2024 May 08.
Article in Chinese | MEDLINE | ID: mdl-38629544

ABSTRACT

Exploring the spatial distribution of land use/coverage (LUCC) and ecosystem carbon reserves in the future of climate change can provide a scientific basis for optimizing the distribution of land resources and formulating social economic sustainable development policies. In this study, we integrated the plaques generating land use simulation (PLUS) model and ecosystem services and weighing comprehensive evaluation (InVEST) model. Based on the CMIP6-based sharing socio-economic path and representative concentration path (SSP-RCP), we evaluated the Loess Plateau for time and space dynamic changes in LUCC and ecosystem carbon reserves, analyzed the impact of driving factors on different regions, and explored the correlation between carbon reserves in various regions. The results showed:① In the future, the three scenarios were similar to the LUCC changes. The area of cultivated land, grassland, and unused land would be reduced to varying degrees, and the construction land had expanded sharply. The increase in the three scenarios was 29.23%-53.56% (SSP126), 34.59%-63.28% (SSP245), and 42.80%-73.27% (SSP585). ② Compared with that in 2020, the carbon reserves of SSP126 sites in 2040 increased by 1.813 8×106 t, and in the remaining scenarios it would continue to decline. By 2060, the grassland carbon reserves in the three scenarios decreased by 13.391×106, 33.548×106, and 85.871×106 t, respectively. ③ From the perspective of space correlation, the carbon reserves of the Loess Plateau were correlated between cities. The difference in future scenarios was not significant. The hotspots were distributed in the middle and north of the research area. There was no obvious cold spot area. ④ The changes in land use were predicted to increase or lose carbon reserves. Forestry, cultivated land, and grassland had more carbon reserves those in than other land types. Increasing their area and restrictions on the conversion of other land types should increase the ecosystem carbon reserves.

4.
Plants (Basel) ; 13(8)2024 Apr 12.
Article in English | MEDLINE | ID: mdl-38674492

ABSTRACT

Two important traits of Chinese cabbage, internode length and budding time, destroy the maintenance of rosette leaves in the vegetative growth stage and affect flowering in the reproductive growth stage. Internodes have received much attention and research in rice due to their effect on lodging resistance, but they are rarely studied in Chinese cabbage. In Chinese cabbage, internode elongation affects not only the maintenance of rosette leaves but also bolting and yield. Budding is also an important characteristic of Chinese cabbage entering reproductive growth. Although many studies have reported on flowering and bolting, studies on bud emergence and the timing of budding are scarce. In this study, the mutant lcc induced by EMS (Ethyl Methane Sulfonate) was used to study internode elongation in the seedling stage and late budding in the budding stage. By comparing the gene expression patterns of mutant lcc and wild-type A03, 2280 differentially expressed genes were identified in the seedling stage, 714 differentially expressed genes were identified in the early budding stage, and 1052 differentially expressed genes were identified in the budding stage. Here, the transcript expression patterns of genes in the plant hormone signaling and clock rhythm pathways were investigated in relation to the regulation of internode elongation and budding in Chinese cabbage. In addition, an F2 population was constructed with the mutants lcc and R500. A high-density genetic map with 1602 marker loci was created, and QTLs for internode length and budding time were identified. Specifically, five QTLs for internode length and five QTLs for budding time were obtained. According to transcriptome data analysis, the internode length candidate gene BraA02g005840.3C (PIN8) and budding time candidate genes BraA02g003870.3C (HY5-1) and BraA02g005190.3C (CHS-1) were identified. These findings provide insight into the regulation of internode length and budding time in Chinese cabbage.

5.
Sci Total Environ ; 928: 172354, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38614330

ABSTRACT

Escalation of ecological concern due to biodegradable plastics has attracted the attention of many contemporary researchers. This study searched to investigate the acute and sub-chronic toxicity of polylactic acid (PLA) and polybutyleneadipate-co-terephthalate (PLA-PBAT) bio-microplastics on 3-month-old zebrafish to elucidate their potential toxic mechanisms. Acute toxicity assessments revealed 96 h-LC50 value of 12.69 mg/L for PLA-PBAT. Sub-chronic exposure of over 21 days revealed deviations in critical behavioral patterns and physiological indicators. In treated groups, weight gain and specific growth rates were significantly lower than those obtained for the control group, such that high doses induced significant reductions in total organ coefficient (p < 0.05). A positive correlation was observed between zebrafish mortality and increased doses. Detailed behavioral evaluations revealed a dose-dependent decrease in the speed and range of swimming, along with modifications in shoaling behavior, anxiety-like responses, and avoidance behaviors. Brain tissues transcriptomic analyses revealed the molecular responses underlying sub-chronic exposure to PLA-PBAT. Totally 702 DEGs and 5 KEGG pathways were significantly identified in low-dose group, with the top 2 significant pathways being ribosome pathway and cytokine-cytokine receptor interaction pathway. Totally 650 DEGs and 5 KEGG pathways were significantly identified in medium-dose group, with the top 2 significant pathways being Herpes simplex virus 1 infection pathway and complement and coagulation cascades pathway. Totally 1778 DEGs and 16 KEGG pathways were significantly identified in high-dose group, with the top 2 significant pathways being metabolism of xenobiotics by cytochrome P450 and drug metabolism - cytochrome P450 pathway. Most significantly enriched pathways are associated with immune responses. The validation of key gene in cytokine-cytokine receptor interaction pathway also confirmed its high correlation with behavioral indicators. These results indicate that PLA-PBAT is likely to cause behavioral abnormalities in zebrafish by triggering immune dysregulation in the brain.


Subject(s)
Behavior, Animal , Microplastics , Polyesters , Water Pollutants, Chemical , Zebrafish , Animals , Zebrafish/physiology , Water Pollutants, Chemical/toxicity , Microplastics/toxicity , Behavior, Animal/drug effects , Biodegradable Plastics
6.
Sensors (Basel) ; 24(8)2024 Apr 14.
Article in English | MEDLINE | ID: mdl-38676135

ABSTRACT

To address the inaccuracy of the Constant Acceleration/Constant Velocity (CA/CV) model as the state equation in describing the relative motion state in UAV relative navigation, an adaptive UAV relative navigation method is proposed, which is based on the UAV attitude information provided by Attitude and Heading Reference System (AHRS). The proposed method utilizes the AHRS output attitude parameters as the benchmark for dead reckoning and derives a relative navigation state equation with attitude error as process noise. By integrating the extended Kalman filter output for relative state estimation and employing an adaptive decision rule designed using the innovation of the filter update phase, the proposed method recalculates motion states deviating from the actual motion using the Tasmanian Devil Optimization (TDO) algorithm. The simulation results show that, compared with the CA/CV model, the proposed method reduces the relative position errors by 12%, 23%, and 32% in the X, Y, and Z directions, respectively, and that it reduces the relative velocity errors by 350%, 330%, and 300%, respectively. There is a significant improvement in the relative navigation accuracy.

7.
BMC Cancer ; 24(1): 507, 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38654231

ABSTRACT

BACKGROUND: Circulating tumor cell (CTC) clusters play a critical role in carcinoma metastasis. However, the rarity of CTC clusters and the limitations of capture techniques have retarded the research progress. In vitro CTC clusters model can help to further understand the biological properties of CTC clusters and their clinical significance. Therefore, it is necessary to establish reliable in vitro methodological models to form CTC clusters whose biological characteristics are very similar to clinical CTC clusters. METHODS: The assays of immunofluorescence, transmission electron microscopy, EdU incorporation, cell adhension and microfluidic chips were used. The experimental metastasis model in mice was used. RESULTS: We systematically optimized the culture methods to form in vitro CTC clusters model, and more importantly, evaluated it with reference to the biological capabilities of reported clinical CTC clusters. In vitro CTC clusters exhibited a high degree of similarity to the reported pathological characteristics of CTC clusters isolated from patients at different stages of tumor metastasis, including the appearance morphology, size, adhesive and tight junctions-associated proteins, and other indicators of CTC clusters. Furthermore, in vivo experiments also demonstrated that the CTC clusters had an enhanced ability to grow and metastasize compared to single CTC. CONCLUSIONS: The study provides a reliable model to help to obtain comparatively stable and qualified CTC clusters in vitro, propelling the studies on tumor metastasis.


Subject(s)
Breast Neoplasms , Cell Culture Techniques , Neoplastic Cells, Circulating , Neoplastic Cells, Circulating/pathology , Animals , Breast Neoplasms/pathology , Humans , Mice , Female , Cell Culture Techniques/methods , Cell Line, Tumor , Neoplasm Metastasis
8.
J Hazard Mater ; 469: 133861, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38430596

ABSTRACT

Microplastics have garnered global attention due to their potential ecological risks. Research shows micro/nano-plastics pollution has adverse effects on plant growth, development, and physiological characteristics. However, the mechanisms underlying these effects remain unclear. The study examined the effects of polystyrene micro/nano-plastics with varying sizes and concentrations on different physiological and biochemical markers of A. thaliana. The indicators assessed include seed viability, growth, chlorophyll content, accumulation of root reactive oxygen species, and root exudates. Using fluorescence labeling, we investigated the absorption and translocation processes of micro/nano-plastics in A. thaliana. We also performed transcriptomic analysis to better understand the particular mechanisms of micro/nano-plastics. It indicated that micro/nano-plastics had an adverse effect on seed germination, especially under high concentration and small particle size treatments. This effect diminished with prolonged exposure. High concentrations at 50 nm and 100 nm treatment groups significantly inhibited the growth. Conversely, low concentrations of 1000 nm had a promoting effect. Exposure to micro/nano-plastics potentially resulted in decreased chlorophyll content, the accumulation of H2O2 in roots, and stimulated root secretion of oxalic acid. Through transcriptomic analysis, the gene expression linked to micro/nano-plastic treatments of varying sizes enriched multiple metabolic pathways, impacting plant growth, development, environmental adaptation, metabolism, pigment synthesis, and stress response.


Subject(s)
Arabidopsis , Polystyrenes , Polystyrenes/toxicity , Microplastics/toxicity , Plastics/metabolism , Arabidopsis/genetics , Arabidopsis/metabolism , Hydrogen Peroxide , Chlorophyll
9.
Asia Pac J Oncol Nurs ; 11(3): 100368, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38426045

ABSTRACT

Effectively addressing the challenges posed by relapsed and refractory diffuse large B-cell lymphoma, particularly when employing autologous hematopoietic stem cell transplantation and CAR-T therapy, requires a comprehensive approach to treatment and nursing. This case report emphasizes a nursing strategy focused on managing neurotoxicity post-CAR-T therapy. Nursing interventions include the identification of neurotoxicity symptoms, neuropsychiatric management, careful support during lumbar puncture and intrathecal administration, psychological assistance, and adaptive nutritional guidance. The diligent application of treatment and nursing care resulted in a remarkable recovery for the patient, as evidenced by the alleviation of central facial paralysis, improvement in swallowing function (from Grade 4 to Grade 2), and enhanced vocalization. Consistent and specialized nursing care is paramount for effectively managing complications, especially neurotoxicity, in patients undergoing CAR-T therapy. A thorough monitoring of symptoms and personalized care contribute to optimizing treatment outcomes and ensuring patient safety.

10.
Chin Med ; 19(1): 45, 2024 Mar 07.
Article in English | MEDLINE | ID: mdl-38454519

ABSTRACT

BACKGROUND: Cutaneous melanoma is a kind of skin malignancy with low morbidity but high mortality. Cryptotanshinone (CPT), an important component of salvia miltiorrhiza has potent anti-tumor activity and also indicates therapeutic effect on dermatosis. So we thought that CPT maybe a potential agent for therapy of cutaneous melanoma. METHODS: B16F10 and A375 melanoma cells were used for in vitro assay. Tumor graft models were made in C57BL/6N and BALB/c nude mice for in vivo assay. Seahorse XF Glycolysis Stress Test Kit was used to detect extracellular acidification rate and oxygen consumption rate. Si-RNAs were used for knocking down adenosine monophosphate-activated protein kinase (AMPK) expression in melanoma cells. RESULTS: CPT could inhibit the proliferation of melanoma cells. Meanwhile, CPT changed the glucose metabolism and inhibited phosphofructokinase (PFK)-mediated glycolysis in melanoma cells to a certain extent. Importantly, CPT activated AMPK and inhibited the expression of hypoxia inducible factor 1α (HIF-1α). Both AMPK inhibitor and silencing AMPK could partially reverse CPT's effect on cell proliferation, cell apoptosis and glycolysis. Finally, in vivo experimental data demonstrated that CPT blocked the growth of melanoma, in which was dependent on the glycolysis-mediated cell proliferation. CONCLUSIONS: CPT activated AMPK and then inhibited PFK-mediated aerobic glycolysis leading to inhibition of growth of cutaneous melanoma. CPT should be a promising anti-melanoma agent for clinical melanoma therapy.

11.
Plants (Basel) ; 13(4)2024 Feb 19.
Article in English | MEDLINE | ID: mdl-38498535

ABSTRACT

Qinting Lake Park has effectively imported Rhododendron varieties from Zhejiang Province. The analytic hierarchy process was employed to devise an evaluation framework to evaluate the ornamental and adaptive features of these species. Subsequently, we conducted a standardized evaluation of 24 species for their ornamental and adaptive traits under controlled cultivation conditions. The findings indicated that the percentage of ornamental flowers in the first-level index was significantly greater than the other two factors, indicating that the ornamental value of flowers was the most important in the evaluation of Rhododendron ornamental value. Among the secondary indicators, the proportion of flower color and flower weight was significantly higher than that of other factors, which had the greatest impact on the evaluation results. The 24 Rhododendron species were classified into two grades based on their ornamental value, as determined by index weights and scoring standards. Rhododendron 'Xueqing', Rhododendron 'Big Qinglian', and Rhododendron 'Jinyang No. 9' exhibited superior ornamental value and demonstrated more favorable suitability for garden applications.

12.
Int J Mol Sci ; 25(5)2024 Feb 26.
Article in English | MEDLINE | ID: mdl-38473926

ABSTRACT

Since its inception, induced pluripotent stem cell (iPSC) technology has been hailed as a powerful tool for comprehending disease etiology and advancing drug screening across various domains. While earlier iPSC-based disease modeling and drug assessment primarily operated at the cellular level, recent years have witnessed a significant shift towards organoid-based investigations. Organoids derived from iPSCs offer distinct advantages, particularly in enabling the observation of disease progression and drug metabolism in an in vivo-like environment, surpassing the capabilities of iPSC-derived cells. Furthermore, iPSC-based cell therapy has emerged as a focal point of clinical interest. In this review, we provide an extensive overview of non-integrative reprogramming methods that have evolved since the inception of iPSC technology. We also deliver a comprehensive examination of iPSC-derived organoids, spanning the realms of the nervous system, cardiovascular system, and oncology, as well as systematically elucidate recent advancements in iPSC-related cell therapies.


Subject(s)
Induced Pluripotent Stem Cells , Induced Pluripotent Stem Cells/metabolism , Organoids/metabolism , Cell- and Tissue-Based Therapy , Cell Differentiation
13.
J Agric Food Chem ; 72(10): 5358-5367, 2024 Mar 13.
Article in English | MEDLINE | ID: mdl-38427033

ABSTRACT

Genome editing tools based on SpCas9 and FnCpf1 have facilitated strain improvements for natural product production and novel drug discovery in Streptomyces. However, due to high toxicity, their editing requires high DNA transformation efficiency, which is unavailable in most streptomycetes. The transformation efficiency of an all-in-one editing tool based on miniature Cas nuclease AsCas12f1 was significantly higher than those of SpCas9 and FnCpf1 in tested streptomycetes, which is due to its small size and weak DNA cleavage activity. Using this tool, in Streptomyces coelicolor, we achieved 100% efficiency for single gene or gene cluster deletion and 46.7 and 40% efficiency for simultaneous deletion of two genes and two gene clusters, respectively. AsCas12f1 was successfully extended to Streptomyces hygroscopicus SIPI-054 for efficient genome editing, in which SpCas9/FnCpf1 does not work well. Collectively, this work offers a low-toxicity, high-efficiency genome editing tool for streptomycetes, particularly those with low DNA transformation efficiency.


Subject(s)
Gene Editing , Streptomyces , CRISPR-Cas Systems , Streptomyces/genetics , DNA
14.
Int J Biol Macromol ; 265(Pt 2): 130822, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38521337

ABSTRACT

Ulcerative colitis (UC) is regarded as a recurring inflammatory disorder of the gastrointestinal tract, for which treatment approaches remain notably limited. In this study, we demonstrated that ginseng polysaccharides (GPs) could alleviate the development of dextran sulfate sodium (DSS)-induced UC as reflected by the ameliorated pathological lesions in the colon. GPs strikingly suppressed the expression levels of multiple inflammatory cytokines, as well as significantly inhibited the infiltration of inflammatory cells. Microbiota-dependent investigations by virtue of 16S rRNA gene sequencing, antibiotic treatment and fecal microbiota transplantation illustrated that GPs treatment prominently restored intestinal microbial balance predominantly through modulating the relative abundance of Lactobacillus. Additionally, GPs remarkably influenced the levels of microbial tryptophan metabolites, diminished the intestinal permeability and strengthened intestinal barrier integrity via inhibiting the 5-HT/HTR3A signaling pathway. Taken together, the promising therapeutic potential of GPs on the development of UC predominantly hinges on the capacity to suppress the expression of inflammatory cytokines as well as to influence Lactobacillus and microbial tryptophan metabolites.


Subject(s)
Colitis, Ulcerative , Colitis , Gastrointestinal Microbiome , Panax , Animals , Mice , Colitis, Ulcerative/drug therapy , Tryptophan , RNA, Ribosomal, 16S , Cytokines , Dextran Sulfate , Disease Models, Animal , Colon , Mice, Inbred C57BL
15.
Chemosphere ; 355: 141744, 2024 May.
Article in English | MEDLINE | ID: mdl-38522669

ABSTRACT

Pesticides pollute natural water reservoirs through persistent accumulation. Therefore, their toxicity and degradability are serious issues. Carbendazim (CBZ) is a pesticide used against fungal infections in agricultural crops, and its overexploitation detrimentally affects aquatic ecosystems and organisms. It is necessary to design a logical, efficient, and field-deployable method for monitoring the amount of CBZ in environmental samples. Herein, a nano-engineered bismuth selenide (Bi2Se3)/functionalized carbon nanofiber (f-CNF) nanocomposite was utilized as an electrocatalyst to fabricate an electrochemical sensing platform for CBZ. Bi2Se3/f-CNF exhibited a substantial electroactive surface area, high electrocatalytic activity, and high conductivity owing to the synergistic interaction of Bi2Se3 with f-CNF. The structural chemical compositions and morphology of the Bi2Se3/f-CNF nanocomposite were confirmed by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and field-emission scanning electron microscopy (FESEM). Electrochemical analysis was carried out using cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and differential pulse voltammetry (DPV). The voltammetry and impedance experiments exposed that the Bi2Se3/f-CNF-modified GCE has attained adequate electrocatalytic function with amended features of electron transportation (Rct = 35.93 Ω) and improved reaction sites (0.082 cm2) accessible by CBZ moiety along with exemplary electrochemical stability (98.92%). The Bi2Se3/f-CNF nanocomposite exhibited higher sensitivity of 0.2974 µA µM-1cm-2 and a remarkably low limit of detection (LOD) of 1.04 nM at a broad linera range 0.001-100 µM. The practicability of the nanocomposite was tested in environmental (tap and pond water) samples, which supports excellent signal amplification with satisfactory recoveries. Hence, the Bi2Se3/f-CNF nanocomposite is a promising electrode modifier for detecting CBZ.


Subject(s)
Benzimidazoles , Bismuth , Carbamates , Carbon , Nanofibers , Selenium Compounds , Carbon/chemistry , Nanofibers/chemistry , Ecosystem , Water , Electrochemical Techniques/methods , Electrodes
16.
Environ Toxicol ; 39(5): 2927-2936, 2024 May.
Article in English | MEDLINE | ID: mdl-38303669

ABSTRACT

Macrophages play an important role in defending the body against invading pathogens. In the face of pathogens, macrophages become activated and release toxic materials that disrupt the pathogens. Macrophage overactivation can lead to severe illness and inflammation. Wogonin has several therapeutic effects, including anti-inflammatory, anticancer, antioxidant, and neuroprotective effects. No studies have investigated the cytotoxic effects of wogonin at concentrations of more than 0.1 mM in RAW264.7 cells. In this study, RAW 264.7 cells were treated with wogonin, which, at concentrations of more than 0.1 mM, had cytotoxic and genotoxic effects in the RAW264.7 cells, leading to apoptosis and necrosis. Further, wogonin at concentrations of more than 0.1 mM induced caspase-3, caspase-8, and caspase-9 activation and mitochondrial dysfunction and death receptor expression. These results suggest that wogonin induces apoptosis through upstream intrinsic and extrinsic pathways by exhibiting cytotoxic and genotoxic effects.


Subject(s)
Apoptosis , Flavanones , Flavanones/pharmacology , Macrophages , DNA Damage
17.
Environ Toxicol ; 39(5): 2970-2979, 2024 May.
Article in English | MEDLINE | ID: mdl-38314619

ABSTRACT

Cyclizine, an over-the-counter and prescription antihistamine, finds widespread application in the prevention and treatment of motion sickness, encompassing symptoms such as nausea, vomiting, dizziness, along with its effectiveness in managing vertigo. However, the overuse or misuse of cyclizine may lead to hallucinations, confusion, tachycardia, and hypertension. The molecular mechanisms underlying cyclizine-induced cytotoxicity and apoptosis remain unclear. During the 24 h incubation duration, RAW264.7 macrophages were exposed to different concentrations of cyclizine. Cytotoxicity was assessed through the lactate dehydrogenase assay. Flow cytometry employing annexin V-fluorescein isothiocyanate and propidium iodide was utilized to evaluate apoptosis and necrosis. Caspase activity and mitochondrial dysfunction were evaluated through a fluorogenic substrate assay and JC-1 dye, respectively. Flow cytometry employing fluorogenic antibodies was utilized to evaluate the release of cytochrome c and expression of death receptor, including tumor necrosis factor-α receptor and Fas receptor. Western blotting was utilized to evaluate the expression of the Bcl2 and Bad apoptotic regulatory proteins. The findings unveiled from the present study demonstrated that cyclizine exerted a concentration-dependent effect on RAW264.7 macrophages, leading to the induction of cytotoxicity, apoptosis, and necrosis. This compound further activated the intrinsic apoptotic pathway by inducing mitochondrial dysfunction, Bcl2/Bad exchange expression, cytochrome c liberation, and activation of caspases contained caspase 3, 8, and 9. Moreover, the activation of the extrinsic apoptotic pathway was observed as cyclizine induced the upregulation of death receptors and increased caspase activities. Based on our investigations, it can be inferred that cyclizine prompts cytotoxicity and apoptosis in RAW264.7 macrophages in a concentration-dependent manner by triggering both the intrinsic and extrinsic apoptotic pathways.


Subject(s)
Cyclizine , Mitochondrial Diseases , Humans , Cyclizine/metabolism , Cyclizine/pharmacology , Cytochromes c/metabolism , Mitochondria/metabolism , Apoptosis , Caspases/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Macrophages , Necrosis/metabolism , Mitochondrial Diseases/metabolism
19.
Int J Biol Sci ; 20(3): 1110-1124, 2024.
Article in English | MEDLINE | ID: mdl-38322116

ABSTRACT

At present, tumor metastasis still remains the leading contributor to high recurrence and mortality in cancer patients. There have been no clinically effective therapeutic strategies for treating patients with metastatic cancer. In recent years, a growing body of evidence has shown that the pre-metastatic niche (PMN) plays a crucial role in driving tumor metastasis. Nevertheless, a clear and detailed understanding of the formation of PMN is still lacking given the fact that PMN formation involves in a wealth of complicated communications and underlying mechanisms between primary tumors and metastatic target organs. Despite that the roles of numerous components including tumor exosomes and extracellular vesicles in influencing the evolution of PMN have been well documented, the involvement of cancer-associated fibroblasts (CAFs) in the tumor microenvironment for controlling PMN formation is frequently overlooked. It has been increasingly recognized that fibroblasts trigger the formation of PMN by virtue of modulating exosomes, metabolism and so on. In this review, we mainly summarize the underlying mechanisms of fibroblasts from diverse origins in exerting impacts on PMN evolution, and further highlight the prospective strategies for targeting fibroblasts to prevent PMN formation.


Subject(s)
Cancer-Associated Fibroblasts , Exosomes , Extracellular Vesicles , Neoplasms , Humans , Prospective Studies , Neoplasms/metabolism , Exosomes/metabolism , Extracellular Vesicles/metabolism , Fibroblasts/metabolism , Cancer-Associated Fibroblasts/metabolism , Tumor Microenvironment , Neoplasm Metastasis/pathology
20.
Int J Biol Macromol ; 261(Pt 2): 129857, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38307438

ABSTRACT

The application of CO2 supercritical fluid (SCF) technology has developed rapidly because of its non-toxic, environmentally friendly, mild reaction conditions and safety. The SCF technology can effectively speed up the reaction process of nano-material synthesis, and maintains a high degree of controllability and repeatability. This study mainly included carboxymethyl chitosan sodium salt (CCS), citral (CT), p-coumaric acid (CA), and ZnSO4 as raw materials to prepare CCS-CT-CA-Zn complex as a pH-responsive agent and was investigated using supercritical fluid technique. The coordination structure of Bridge-CCS-CT-CH3COO-CA-Zn-Schiff base/OH and the morphology of the complex agents were verified. The prepared CCS-CT-CA-Zn complex showed good dispersion and uniformity (mean size: 852 ± 202 nm, PdI: 0.301, and mean zeta potential: -31 ± 6 mV). Also, it has a good pH responsive release in an acid environment. Besides, both of CCS-CT-CA-Zn complex (DS-B) and its decomposed mixture in acid (DS-A) demonstrated significant antioxidant and anti-vibrio activity. Moreover, both DS-B complex and DS-A mixture inhibited biofilm formation, swimming, and swarming motilities of V. parahaemolyticus in a dose-dependent manner. This work will provide a scientific basis for the further design and development of natural products derived antibacterial-antioxidant complex agents, food additives and feed additives.


Subject(s)
Acyclic Monoterpenes , Chitosan , Chitosan/pharmacology , Chitosan/chemistry , Zinc/chemistry , Schiff Bases/pharmacology , Schiff Bases/chemistry , Antioxidants/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Hydrogen-Ion Concentration
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