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1.
Sci Total Environ ; 954: 176715, 2024 Oct 03.
Article in English | MEDLINE | ID: mdl-39368502

ABSTRACT

Neonicotinoids (NEOs) are commonly used pesticides in agriculture. Urban parks containing numerous green plants and flowers also require NEOs for pest control. However, information on the distribution patterns and environmental risks of NEOs and their metabolites in urban park soils has yet to be discovered, which seriously limits the comprehensive evaluation of the potential hazards of NEOs. Our study explored the occurrence and distribution patterns of ten NEOs and five major metabolites in park soils from Guangzhou, Shijiazhuang, and Urumqi of China. At least three NEOs were detected in 95 % of soil samples, with the sum of all NEOs (∑10NEOs) ranging from 2.21 to 204 ng/g. Guangzhou has the highest levels of ∑10NEOs (median: 52.1 ng/g), followed by Urumqi (49.3 ng/g) and Shijiazhuang (21.7 ng/g). The top three most common NEOs in all three cities are imidacloprid, acetamiprid, and thiacloprid, which together account for 67 % to 70 % of ∑10NEOs. The levels of the metabolites of NEOs show a significant positive correlation with their corresponding parent NEOs. These NEOs pose detrimental effects to non-targeted invertebrates in the soil. Our findings raise concern about the environmental risks posed by NEO exposure to humans and other organisms in urban parks.

2.
Mol Biotechnol ; 2024 Sep 10.
Article in English | MEDLINE | ID: mdl-39254869

ABSTRACT

As a two-dimensional material, gold nanotriangles (GNTs) are rarely studied in the field of gene delivery. In this study, a temperature-responsive GNTs was developed as a novel carrier for gene delivery. The temperature-sensitive copolymer PNIPAm-g-PEI was grafted onto the surface of GNTs to construct a PNIPAm-g-PEI/GNTs composite controllable release platform. The lower critical solution temperature (LCST) of PNIPAm-g-PEI/GNTs was found to be 42 °C, and the particle size of PNIPAm-g-PEI/GNTs was 150 nm at this temperature. Gel electrophoresis experiments showed that PNIPAm-g-PEI/GNTs completely condensed DNA at 20 µg/mL, and PNIPAm-g-PEI/GNTs promoted the release of DNA under laser irradiation. Luciferase and green fluorescent protein reporter gene assays demonstrated that the transfection efficiency of PNIPAm-g-PEI/GNTs was 1.5 and 7.2 times that of PEI, respectively. These results demonstrated the promising potential of temperature-responsive GNTs as effective and safe gene delivery vectors.

3.
Cell Death Differ ; 31(9): 1184-1201, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39103535

ABSTRACT

Ferroptosis holds significant potential for application in cancer therapy. However, ferroptosis inducers are not cell-specific and can cause phospholipid peroxidation in both tumor and non-tumor cells. This limitation greatly restricts the use of ferroptosis therapy as a safe and effective anticancer strategy. Our previous study demonstrated that macrophages can engulf ferroptotic cells through Toll-like receptor 2 (TLR2). Despite this advancement, the precise mechanism by which phospholipid peroxidation in macrophages affects their phagocytotic capability during treatment of tumors with ferroptotic agents is still unknown. Here, we utilized flow sorting combined with redox phospholipidomics to determine that phospholipid peroxidation in tumor microenvironment (TME) macrophages impaired the macrophages ability to eliminate ferroptotic tumor cells by phagocytosis, ultimately fostering tumor resistance to ferroptosis therapy. Mechanistically, the accumulation of phospholipid peroxidation in the macrophage endoplasmic reticulum (ER) repressed TLR2 trafficking to the plasma membrane and caused its retention in the ER by disrupting the interaction between TLR2 and its chaperone CNPY3. Subsequently, this ER-retained TLR2 recruited E3 ligase MARCH6 and initiated the proteasome-dependent degradation. Using redox phospholipidomics, we identified 1-steaoryl-2-15-HpETE-sn-glycero-3-phosphatidylethanolamine (SAPE-OOH) as the crucial mediator of these effects. Conclusively, our discovery elucidates a novel molecular mechanism underlying macrophage phospholipid peroxidation-induced tumor resistance to ferroptosis therapy and highlights the TLR2-MARCH6 axis as a potential therapeutic target for cancer therapy.


Subject(s)
Ferroptosis , Lipid Peroxidation , Macrophages , Phagocytosis , Phospholipids , Phospholipids/metabolism , Macrophages/metabolism , Animals , Mice , Humans , Toll-Like Receptor 2/metabolism , Tumor Microenvironment , Cell Line, Tumor , Mice, Inbred C57BL , Neoplasms/metabolism , Neoplasms/pathology , RAW 264.7 Cells
4.
Technol Cancer Res Treat ; 23: 15330338241274289, 2024.
Article in English | MEDLINE | ID: mdl-39149935

ABSTRACT

Introduction: In recent years, the development of drug-eluting embolization beads that can be imaged has become a hot research topic in regard to meeting clinical needs. In our previous study, we successfully developed nano-assembled microspheres (NAMs) for multimodal imaging purposes. NAMs can not only be visualized under CT/MR/Raman imaging but can also load clinically required doses of doxorubicin. It is important to systematically compare the pharmacokinetics of NAMs with those of commercially available DC Beads and CalliSpheres to evaluate the clinical application potential of NAMs. Methods: In our study, we compared NAMs with two types of drug-eluting beads (DEBs) in terms of irinotecan, drug-loading capacity, release profiles, microsphere diameter variation, and morphological characteristics. Results: Our results indicate that NAMs had an irinotecan loading capacity similar to those of DC Beads and CalliSpheres but exhibited better sustained release in vitro. Conclusion: NAMs have great potential for application in transcatheter arterial chemoembolization for the treatment of colorectal cancer liver metastases.


Subject(s)
Irinotecan , Microspheres , Multimodal Imaging , Irinotecan/administration & dosage , Irinotecan/pharmacology , Humans , Multimodal Imaging/methods , Drug Carriers/chemistry , Drug Liberation , Chemoembolization, Therapeutic/methods , Drug Delivery Systems , Liver Neoplasms/secondary , Liver Neoplasms/drug therapy , Liver Neoplasms/diagnostic imaging , Camptothecin/analogs & derivatives , Camptothecin/administration & dosage , Camptothecin/pharmacology
5.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 32(4): 1186-1190, 2024 Aug.
Article in Chinese | MEDLINE | ID: mdl-39192417

ABSTRACT

OBJECTIVE: To observe the genetic variation of SH2B3 in patients with myeloid neoplasms. METHODS: The results of targeted DNA sequencing associated with myeloid neoplasms in the Department of Hematology, Xuanwu Hospital, Capital Medical University from November 2017 to November 2022 were retrospectively analyzed, and the patients with SH2B3 gene mutations were identified. The demographic and clinical data of these patients were collected, and characteristics of SH2B3 gene mutation, co-mutated genes and their correlations with diseases were analyzed. RESULTS: The sequencing results were obtained from 1 005 patients, in which 19 patients were detected with SH2B3 gene mutation, including 18 missense mutations (94.74%), 1 nonsense mutation (5.26%), and 10 patients with co-mutated genes (52.63%). Variant allele frequency (VAF) ranged from 0.03 to 0.66. The highest frequency mutation was p.Ile568Thr (5/19, 26.32%), with an average VAF of 0.49, involving 1 case of MDS/MPN-RS (with SF3B1 mutation), 1 case of MDS-U (with SF3B1 mutation), 1 case of aplastic anemia with PNH clone (with PIGA and KMT2A mutations), 2 cases of MDS-MLD (1 case with SETBP1 mutation). The other mutations included p.Ala567Thr in 2 cases (10.53%), p.Arg566Trp, p.Glu533Lys, p.Met437Arg, p.Arg425Cys, p.Glu314Lys, p.Arg308*, p.Gln294Glu, p.Arg282Gln, p.Arg175Gln, p.Gly86Cys, p.His55Asn and p.Gln54Pro in 1 case each. CONCLUSION: A wide distribution of genetic mutation sites and low recurrence of SH2B3 is observed in myeloid neoplasms, among of them, p.Ile568Thr mutation is detected with a higher incidence and often coexists with characteristic mutations of other diseases.


Subject(s)
Adaptor Proteins, Signal Transducing , Intracellular Signaling Peptides and Proteins , Mutation , Humans , Adaptor Proteins, Signal Transducing/genetics , Retrospective Studies , Intracellular Signaling Peptides and Proteins/genetics , Genetic Variation , Gene Frequency , Mutation, Missense , Myeloproliferative Disorders/genetics , Male , Hematologic Neoplasms/genetics
6.
Cell Rep ; 43(8): 114636, 2024 Aug 27.
Article in English | MEDLINE | ID: mdl-39154340

ABSTRACT

Inflammatory bowel disease (IBD) has high prevalence in Western counties. The high fat content in Western diets is one of the leading causes for this prevalence; however, the underlying mechanisms have not been fully defined. Here, we find that high-fat diet (HFD) induces ferroptosis of intestinal regulatory T (Treg) cells, which might be the key initiating step for the disruption of immunotolerance and the development of colitis. Compared with effector T cells, Treg cells favor lipid metabolism and prefer polyunsaturated fatty acids (PUFAs) for the synthesis of membrane phospholipids. Therefore, consumption of HFD, which has high content of PUFAs such as arachidonic acid, cultivates vulnerable Tregs that are fragile to lipid peroxidation and ferroptosis. Treg-cell-specific deficiency of GPX4, the key enzyme in maintaining cellular redox homeostasis and preventing ferroptosis, dramatically aggravates the pathogenesis of HFD-induced IBD. Taken together, these studies expand our understanding of IBD etiology.


Subject(s)
Colitis , Diet, High-Fat , Fatty Acids, Unsaturated , Ferroptosis , Mice, Inbred C57BL , Phospholipid Hydroperoxide Glutathione Peroxidase , T-Lymphocytes, Regulatory , Animals , Diet, High-Fat/adverse effects , Ferroptosis/drug effects , Colitis/pathology , Colitis/metabolism , Colitis/chemically induced , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , Fatty Acids, Unsaturated/metabolism , Mice , Phospholipid Hydroperoxide Glutathione Peroxidase/metabolism , Male , Lipid Peroxidation/drug effects
7.
Int J Environ Health Res ; : 1-13, 2024 Jul 23.
Article in English | MEDLINE | ID: mdl-39041841

ABSTRACT

Evidence on the impacts of PM1, PM2.5, and PM10 on the hospital admissions, length of hospital stays (LOS), and hospital expenses among patients with cardiovascular disease (CVD) is still limited in China, especially in rural areas. This study was performed in eight counties of Fuyang from 1 January 2015 to 30 June 2017. We use a three-stage time-series analysis to explore the effects of short-term exposure to PM1, PM2.5, and PM10 on hospital admissions, LOS, and hospital expenses for CVDs. An increment of 10 ug/m3 in PM1, PM2.5, and PM10 corresponded to an increment of 1.82% (95% CI: 1.34, 2.30), 0.96% (95% CI: 0.44, 1.48), and 0.79% (95% CI: 0.63%, 0.95%) in CVD hospital admissions, respectively. We observed that daily concentrations of PMs were associated with an increase in hospital admissions, LOS, and expenses for CVDs. Sustained endeavors are required to reduce air pollution so as to attenuate disease burdens from CVDs.

8.
J Obstet Gynaecol Can ; : 102585, 2024 Jun 13.
Article in English | MEDLINE | ID: mdl-38878822

ABSTRACT

OBJECTIVES: This study investigates experiences of medical students across Canada related to consent for educational sensitive (i.e., pelvic, rectal) exams under anesthesia (EUAs). METHODS: A bilingual online questionnaire was developed and distributed to medical students across Canada. RESULTS: Of 134 respondents, 63% had performed a pelvic EUA, 35% a rectal EUA, and 11% another sensitive EUA during their training. For those who had performed pelvic EUA, 28% were unsure if consent had taken place, 26% reported no specific consent, 20% reported specific consent, and 25% had mixed experiences of consent. For rectal EUAs, 48% reported no specific consent, 37% were unsure if consent had taken place, 13% reported that there had been specific consent, and 2% reported mixed experiences. Most respondents were uncomfortable (36%) or not sure if they were comfortable (32%) with how the consent process was handled for student pelvic EUAs; 31% were comfortable. In open-ended responses, respondents described experiences related to variability, discomfort, and authority. CONCLUSIONS: Non-consensual educational sensitive EUAs continue to take place in medical training across Canada, although practices of consent are highly variable. The majority of respondents reported being uncomfortable or unsure if they were comfortable with how consent for educational sensitive EUAs was practised during their training, and some respondents struggled to express their discomfort given the power dynamics at play.

9.
Biomacromolecules ; 25(6): 3566-3582, 2024 Jun 10.
Article in English | MEDLINE | ID: mdl-38780026

ABSTRACT

Diabetic foot ulcers (DFUs), a prevalent complication of diabetes mellitus, may result in an amputation. Natural and renewable hydrogels are desirable materials for DFU dressings due to their outstanding biosafety and degradability. However, most hydrogels are usually only used for wound repair and cannot be employed to monitor motion because of their inherent poor mechanical properties and electrical conductivity. Given that proper wound stretching is beneficial for wound healing, the development of natural hydrogel patches integrated with wound repair properties and motion monitoring was expected to achieve efficient and accurate wound healing. Here, we designed a dual-network (chitosan and sodium alginate) hydrogel embedded with lignin-Ag and quercetin-melanin nanoparticles to achieve efficient wound healing and motion monitoring. The double network formed by the covalent bond and electrostatic interaction confers the hydrogel with superior mechanical properties. Instead of the usual chemical reagents, genipin extracted from Gardenia was used as a cross-linking agent for the hydrogel and consequently improved its biosafety. Furthermore, the incorporation of lignin-Ag nanoparticles greatly enhanced the mechanical strength, antibacterial efficacy, and conductivity of the hydrogel. The electrical conductivity of hydrogels gives them the capability of motion monitoring. The motion sensing mechanism is that stretching of the hydrogel induced by motion changes the conductivity of the hydrogel, thus converting the motion into an electrical signal. Meanwhile, quercetin-melanin nanoparticles confer exceptional adhesion, antioxidant, and anti-inflammatory properties to the hydrogels. The system ultimately achieved excellent wound repair and motion monitoring performance and was expected to be used for stretch-assisted safe and accurate wound repair in the future.


Subject(s)
Chitosan , Electric Conductivity , Hydrogels , Wound Healing , Hydrogels/chemistry , Wound Healing/drug effects , Chitosan/chemistry , Animals , Quercetin/chemistry , Quercetin/pharmacology , Melanins/chemistry , Silver/chemistry , Diabetic Foot/therapy , Diabetic Foot/drug therapy , Mice , Alginates/chemistry , Metal Nanoparticles/chemistry , Humans , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Iridoids
10.
Phytomedicine ; 129: 155613, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38703659

ABSTRACT

BACKGROUND: Psychological stress is associated with various diseases including liver dysfunction, yet effective intervention strategies remain lacking due to the unrevealed pathogenesis mechanism. PURPOSE: This study aims to explore the relevance between BMAL1-controlled circadian rhythms and lipoxygenase 15 (ALOX15)-mediated phospholipids peroxidation in psychological stress-induced liver injury, and to investigate whether hepatocyte phospholipid peroxidation signaling is involved in the hepatoprotective effects of a Chinese patent medicine, Pien Tze Huang (PZH). METHODS: Restraint stress models were established to investigate the underlying molecular mechanisms of psychological stress-induced liver injury and the hepatoprotective effects of PZH. Redox lipidomics based on liquid chromatography-tandem mass spectrometry was applied for lipid profiling. RESULTS: The present study discovered that acute restraint stress could induce liver injury. Notably, lipidomic analysis confirmed that phospholipid peroxidation was accumulated in the livers of stressed mice. Additionally, the essential core circadian clock gene Brain and Muscle Arnt-like Protein-1 (Bmal1) was altered in stressed mice. Circadian disruption in mice, as well as BMAL1-overexpression in human HepaRG cells, also appeared to have a significant increase in phospholipid peroxidation, suggesting that stress-induced liver injury is closely related to circadian rhythm and phospholipid peroxidation. Subsequently, arachidonate 15-lipoxygenase (ALOX15), a critical enzyme that contributed to phospholipid peroxidation, was screened as a potential regulatory target of BMAL1. Mechanistically, BMAL1 promoted ALOX15 expression via direct binding to an E-box-like motif in the promoter. Finally, this study revealed that PZH treatment significantly relieved pathological symptoms of psychological stress-induced liver injury with a potential mechanism of alleviating ALOX15-mediated phospholipid peroxidation. CONCLUSION: Our findings illustrate the critical role of BMAL1-triggered phospholipid peroxidation in psychological stress-induced liver injury and provide new insight into treating psychological stress-associated liver diseases by TCM intervention.


Subject(s)
Drugs, Chinese Herbal , Hepatocytes , Lipid Peroxidation , Phospholipids , Stress, Psychological , Animals , Drugs, Chinese Herbal/pharmacology , Hepatocytes/metabolism , Hepatocytes/drug effects , Male , Stress, Psychological/drug therapy , Mice , Lipid Peroxidation/drug effects , Phospholipids/metabolism , Humans , Mice, Inbred C57BL , Signal Transduction/drug effects , Arachidonate 15-Lipoxygenase/metabolism , ARNTL Transcription Factors/metabolism , Circadian Rhythm/drug effects , Liver/metabolism , Liver/drug effects
11.
Nat Chem Biol ; 20(10): 1341-1352, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38720107

ABSTRACT

Whether stem-cell-like cancer cells avert ferroptosis to mediate therapy resistance remains unclear. In this study, using a soft fibrin gel culture system, we found that tumor-repopulating cells (TRCs) with stem-cell-like cancer cell characteristics resist chemotherapy and radiotherapy by decreasing ferroptosis sensitivity. Mechanistically, through quantitative mass spectrometry and lipidomic analysis, we determined that mitochondria metabolic kinase PCK2 phosphorylates and activates ACSL4 to drive ferroptosis-associated phospholipid remodeling. TRCs downregulate the PCK2 expression to confer themselves on a structural ferroptosis-resistant state. Notably, in addition to confirming the role of PCK2-pACSL4(T679) in multiple preclinical models, we discovered that higher PCK2 and pACSL4(T679) levels are correlated with better response to chemotherapy and radiotherapy as well as lower distant metastasis in nasopharyngeal carcinoma cohorts.


Subject(s)
Ferroptosis , Phospholipids , Humans , Phospholipids/metabolism , Animals , Cell Line, Tumor , Coenzyme A Ligases/metabolism , Mice , Phosphorylation , Drug Resistance, Neoplasm , Neoplastic Stem Cells/metabolism , Neoplastic Stem Cells/pathology
12.
Int J Biol Macromol ; 268(Pt 2): 131678, 2024 May.
Article in English | MEDLINE | ID: mdl-38657921

ABSTRACT

BACKGROUND: Glia maturation factor beta (GMFB) is a growth and differentiation factor that acts as an intracellular regulator of signal transduction pathways. The small ubiquitin-related modifier (SUMO) modification, SUMOylation, is a posttranslational modification (PTM) that plays a key role in protein subcellular localization, stability, transcription, and enzymatic activity. Recent studies have highlighted the importance of SUMOylation in the inflammation and progression of numerous diseases. However, the relationship between GMFB and SUMOylation is unclear. RESULTS: Here, we report for the first time that GMFB and SUMO1 are markedly increased in retinal pigment epithelial (RPE) cells at the early stage of diabetes mellitus (DM) under hyperglycemia. The GMFΒ protein could be mono-SUMOylated by SUMO1 at the K20, K35, K58 or K97 sites. SUMOylation of GMFB led to its increased protein stability and subcellular translocation. Furthermore, deSUMOylation of GMFΒ downregulates multiple signaling pathways, including the Jak-STAT signaling pathway, p38 pathway and NF-kappa B signaling pathway. CONCLUSIONS: This work provides novel insight into the role of SUMOylated GMFB in RPE cells and provides a novel therapeutic target for diabetic retinopathy (DR).


Subject(s)
Hyperglycemia , Protein Stability , Retinal Pigment Epithelium , Signal Transduction , Sumoylation , Humans , Cell Line , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/pathology , Epithelial Cells/metabolism , Hyperglycemia/metabolism , NF-kappa B/metabolism , Retinal Pigment Epithelium/metabolism , SUMO-1 Protein/metabolism , Glia Maturation Factor
13.
J Med Internet Res ; 26: e47017, 2024 Apr 01.
Article in English | MEDLINE | ID: mdl-38557504

ABSTRACT

The mortality rate in intensive care units (ICUs) is notably high, with patients often relying on surrogates for critical medical decisions due to their compromised state. This paper provides a comprehensive overview of eHealth. The challenges of applying eHealth tools, including economic disparities and information inaccuracies are addressed. This study then introduces eHealth literacy and the assessment tools to evaluate users' capability and literacy levels in using eHealth resources. A clinical scenario involving surrogate decision-making is presented. This simulated case involves a patient with a hemorrhagic stroke who has lost consciousness and requires medical procedures such as tracheostomy. However, due to the medical surrogate's lack of familiarity with eHealth devices and limited literacy in using eHealth resources, difficulties arise in assisting the patient in making medical decisions. This scenario highlights challenges related to eHealth literacy and solution strategies are proposed. In conclusion, effective ICU decision-making with eHealth tools requires a careful balance between efficiency with inclusivity. Tailoring communication strategies and providing diverse materials are essential for effective eHealth decision resources in the ICU setting. Health professionals should adopt a patient-centered approach to enhance the decision-making experience, particularly for individuals with limited eHealth literacy.


Subject(s)
Health Literacy , Telemedicine , Humans , Decision Making , Intensive Care Units , Communication , Health Personnel
14.
J Genet Genomics ; 51(8): 801-810, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38570113

ABSTRACT

KCNA1 is the coding gene for Kv1.1 voltage-gated potassium-channel α subunit. Three variants of KCNA1 have been reported to manifest as paroxysmal kinesigenic dyskinesia (PKD), but the correlation between them remains unclear due to the phenotypic complexity of KCNA1 variants as well as the rarity of PKD cases. Using the whole exome sequencing followed by Sanger sequencing, we screen for potential pathogenic KCNA1 variants in patients clinically diagnosed with paroxysmal movement disorders and identify three previously unreported missense variants of KCNA1 in three unrelated Chinese families. The proband of one family (c.496G>A, p.A166T) manifests as episodic ataxia type 1, and the other two (c.877G>A, p.V293I and c.1112C>A, p.T371A) manifest as PKD. The pathogenicity of these variants is confirmed by functional studies, suggesting that p.A166T and p.T371A cause a loss-of-function of the channel, while p.V293I leads to a gain-of-function with the property of voltage-dependent gating and activation kinetic affected. By reviewing the locations of PKD-manifested KCNA1 variants in Kv1.1 protein, we find that these variants tend to cluster around the pore domain, which is similar to epilepsy. Thus, our study strengthens the correlation between KCNA1 variants and PKD and provides more information on genotype-phenotype correlations of KCNA1 channelopathy.


Subject(s)
Dystonia , Kv1.1 Potassium Channel , Mutation, Missense , Pedigree , Humans , Kv1.1 Potassium Channel/genetics , Male , Female , Dystonia/genetics , Dystonia/pathology , Mutation, Missense/genetics , Exome Sequencing , Loss of Function Mutation/genetics , Adult , Gain of Function Mutation/genetics , Child , Adolescent , Genetic Predisposition to Disease , HEK293 Cells , Ataxia , Myokymia
15.
Phytomedicine ; 128: 155475, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38492368

ABSTRACT

BACKGROUND: The intricate interactions between chronic psychological stress and susceptibility to breast cancer have been recognized, yet the underlying mechanisms remain unexplored. Danzhi Xiaoyao Powder (DZXY), a traditional Chinese medicine (TCM) formula, has found clinical utility in the treatment of breast cancer. Macrophages, as the predominant immune cell population within the tumor microenvironment (TME), play a pivotal role in orchestrating tumor immunosurveillance. Emerging evidence suggests that lipid oxidation accumulation in TME macrophages, plays a critical role in breast cancer development and progression. However, a comprehensive understanding of the pharmacological mechanisms and active components of DZXY related to its clinical application in the treatment of stress-aggravated breast cancer remains elusive. PURPOSE: This study sought to explore the plausible regulatory mechanisms and identify the key active components of DZXY contributing to its therapeutic efficacy in the context of breast cancer. METHODS: Initially, we conducted an investigation into the relationship between the phagocytic capacity of macrophages damaged by psychological stress and phospholipid peroxidation using flow cytometry and LC-MS/MS-based phospholipomics. Subsequently, we evaluated the therapeutic efficacy of DZXY based on the results of the tumor size, tumor weight, the phospholipid peroxidation pathway and phagocytosis of macrophage. Additionally, the target-mediated characterization strategy based on binding of arachidonate 15-lipoxygenase (ALOX15) to phosphatidylethanolamine-binding protein-1 (PEBP1), including molecular docking analysis, microscale thermophoresis (MST) assay, co-immunoprecipitation analysis and activity verification, has been further implemented to reveal the key bio-active components in DZXY. Finally, we evaluated the therapeutic efficacy of isochlorogenic acid C (ICAC) based on the results of tumor size, tumor weight, the phospholipid peroxidation pathway, and macrophage phagocytosis in vivo. RESULTS: The present study demonstrated that phospholipid peroxides, as determined by LC-MS/MS-based phospholipidomics, triggered in macrophages, which in turn compromised their capacity to eliminate tumor cells through phagocytosis. Furthermore, we elucidate the mechanism behind stress-induced PEBP1 to form a complex with ALOX15, thereby mediating membrane phospholipid peroxidation in macrophages. DZXY, demonstrates potent anti-breast cancer therapeutic effects by disrupting the ALOX15/PEBP1 interaction and inhibiting phospholipid peroxidation, ultimately enhancing macrophages' phagocytic capability towards tumor cells. Notably, ICAC emerged as a promising active component in DZXY, which can inhibit the ALOX15/PEBP1 interaction, thereby mitigating phospholipid peroxidation in macrophages. CONCLUSION: Collectively, our findings elucidate stress increases the susceptibility of breast cancer by driving lipid peroxidation of macrophages and suggest the ALOX15/PEBP1 complex as a promising intervention target for DZXY.


Subject(s)
Arachidonate 15-Lipoxygenase , Drugs, Chinese Herbal , Lipid Peroxidation , Macrophages , Phospholipids , Tumor Microenvironment , Drugs, Chinese Herbal/pharmacology , Tumor Microenvironment/drug effects , Animals , Macrophages/drug effects , Macrophages/metabolism , Female , Mice , Arachidonate 15-Lipoxygenase/metabolism , Lipid Peroxidation/drug effects , Humans , Breast Neoplasms/drug therapy , Stress, Psychological/drug therapy , Molecular Docking Simulation , Phagocytosis/drug effects , Mice, Inbred BALB C , RAW 264.7 Cells
16.
Front Med (Lausanne) ; 11: 1382100, 2024.
Article in English | MEDLINE | ID: mdl-38545507

ABSTRACT

Purpose: To present the outcomes of a new technique for intrascleral fixation of a flanged three-piece foldable intraocular lens (IOL) without a conjunctival incision. Materials and methods: We retrospectively reviewed a consecutive series of 12 eyes of 12 patients who underwent scleral IOL fixation using this technique. Results: The follow-up period ranged 3-12 months. There was a significant improvement in best-corrected visual acuity, from 0.8 (1.6) logarithm of the minimum angle of resolution (logMAR) preoperatively to 0.45 (0.8) logMAR at the final postoperative follow-up (p = 0.012). Notable complications included one case of pupillary IOL capture and increased intraocular pressure. Conclusion: Our novel technique is a viable solution for managing secondary IOL fixation, enabling the use of a wider variety of IOLs and simplifying the reposition process for dislocated three-piece IOLs. This approach has the potential to lower complication rates and enhance patients' recovery.

17.
Free Radic Biol Med ; 216: 46-49, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38458392

ABSTRACT

Since the discovery of tocopherols a century ago, α-tocopherol has been distinguished for its unique biological functions. In this study, we aim to elucidate the unique characteristics of α-tocopherol from a chemical perspective. Utilizing density functional theory (DFT) calculations, we evaluated the thermodynamic and kinetic properties of tocopherols, tocotrienols and their oxidation products. Our findings highlight the superior thermodynamic and kinetic properties of α-tocopherol. Although tocopherol substrates generally exhibit similar reactivities, α-tocopherol is distinguished by a larger gap between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) in intermediates, indicating a potential for greater energy release and favoring reaction progression. Moreover, α-tocopherol shows enhanced efficiency in quenching radical intermediates, especially when combined with vitamin C. All these dates provide valuable support for the naming of vitamin E.


Subject(s)
Antioxidants , Tocotrienols , Antioxidants/chemistry , Vitamin E , alpha-Tocopherol , Tocopherols
18.
Nutr Metab Cardiovasc Dis ; 34(6): 1571-1580, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38418351

ABSTRACT

BACKGROUND AND AIM: The present study aimed to investigate whether the mitochondrial KATP channel contributes to angiotensin II (Ang II)-induced vascular dysfunction, the development of hypertension, and atherosclerosis. METHODS AND RESULTS: ApoE (-/-) mice fed a high-fat diet were chronically infused with Ang II for eight weeks and concomitantly treated with losartan (ARB), apocynin, or 5-hydroxy decanoate (5-HD), or 3-methyladenine (3-MA). Systolic blood pressure was measured, and pathological changes of aortic or liver tissue were observed. Nitric oxide (NO), superoxide dismutase 2 (SOD2) levels and vasorelaxation rate were measured, and protein and mRNA expressions were examined by western blot and RT-PCR. Ang II-induced development of hypertension was suppressed not only by ARB, and apocynin but also by 5-HD or 3-MA. Ang II infusion decreased aortic NO production and relaxation, as well as SOD2 activity in liver, which were improved by all treatments. In addition, Ang II-induced activation of autophagy was suppressed by 5-HD in aortic tissue, furthermore, Ang II increases the atherosclerotic index in plasma and exacerbates the development of atherosclerosis by increases of fat deposition in the aorta and liver. Lipid metabolism-related mRNA expressions (LXR-α, LDLR, SRBI, Acca, and FASN) were changed by Ang II. Similarly, not only ARB, and apocynin, but also 5-HD and 3-MA suppressed Ang II-induced these changes. CONCLUSIONS: Our present findings evidence that mitochondrial KATP channel-mediated autophagy contributes to Ang II-induced vascular dysfunction, development of hypertension, and atherosclerosis.


Subject(s)
Angiotensin II , Atherosclerosis , Autophagy , Hypertension , Nitric Oxide , Superoxide Dismutase , Animals , Autophagy/drug effects , Male , Superoxide Dismutase/metabolism , Superoxide Dismutase/genetics , Hypertension/physiopathology , Hypertension/chemically induced , Hypertension/metabolism , Hypertension/pathology , Nitric Oxide/metabolism , Atherosclerosis/chemically induced , Atherosclerosis/pathology , Atherosclerosis/metabolism , Atherosclerosis/genetics , Atherosclerosis/physiopathology , Mice, Knockout, ApoE , Mice, Inbred C57BL , Aorta/drug effects , Aorta/pathology , Aorta/metabolism , Aorta/physiopathology , Blood Pressure/drug effects , Mice , Disease Models, Animal , Liver/metabolism , Liver/pathology , Liver/drug effects , Vasodilation/drug effects , Diet, High-Fat , Potassium Channels
19.
Plant Cell Environ ; 47(5): 1575-1591, 2024 May.
Article in English | MEDLINE | ID: mdl-38269615

ABSTRACT

The spike growth phase is critical for the establishment of fertile floret (grain) numbers in wheat (Triticum aestivum L.). Then, how to shorten the spike growth phase and increase grain number synergistically? Here, we showed high-resolution analyses of floret primordia (FP) number, morphology and spike transcriptomes during the spike growth phase under three light regimens. The development of all FP in a spike could be divided into four distinct stages: differentiation (Stage I), differentiation and morphology development concurrently (Stage II), morphology development (Stage III), and polarization (Stage IV). Compared to the short photoperiod, the long photoperiod shortened spike growth and stimulated early flowering by shortening Stage III; however, this reduced assimilate accumulation, resulting in fertile floret loss. Interestingly, long photoperiod supplemented with red light shortened the time required to complete Stages I-II, then raised assimilates supply in the spike and promoted anther development before polarization initiation, thereby increasing fertile FP number during Stage III, and finally maintained fertile FP development during Stage IV until they became fertile florets via a predicted dynamic gene network. Our findings proposed a light regimen, critical stages and candidate regulators that achieved a shorter spike growth phase and a higher fertile floret number in wheat.


Subject(s)
Flowers , Triticum , Flowers/physiology , Triticum/physiology , Gene Expression Profiling , Edible Grain/genetics , Fertility , Transcriptome/genetics
20.
Int J Biol Macromol ; 264(Pt 1): 129762, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38281535

ABSTRACT

Lignin, as an amorphous three-dimensional aromatic polymer, was able to self-assemble into lignin nanoparticles (LNPs) to realize valorization of lignin. Here, lignin-xylan extractives were extracted from grape seed (GS) and poplar by acidic THF at room temperature, and effectively produced lignin-xylan nanospheres via spin evaporation. The morphology and chemical properties of nanospheres were determined by its natural origins, consequently influencing its application. For the lignin-xylan extractive from grape seed, the lignin was composed of guaiacyl (G) and p-hydroxylphenyl (H) units and the hollowed nanospheres (GS-LNPs) with 362.72 nm diameter was produced. The extractive from poplar was composed of G-syringyl (S) typed lignin (80.30 %) and xylan (12.33 %), that can assemble into LNPs with smaller size (229.87 nm), better PDI (0.1), and light color. The hybrid particles showed the qualities of lignin and xylan, that properties led to the LNPs@PVA composite films with UV-blocking capability, strong mechanical strength and hydrophobicity, and transparency ability of visible light. P-LNPs showed better performance as the film additives, due to its lower particles size and high content of unconjugated -OH from xylan. Xylan was significant in the composite films, and lowering the xylan content resulted in the decrease of the composite film's mechanical properties and hydrophobicity.


Subject(s)
Lignin , Nanospheres , Lignin/chemistry , Xylans/chemistry , Polymers
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