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Nanoplastics (NPs) pollution has become a global environmental problem, raising numerous health concerns. However, the cardiotoxicity of NPs exposure and the underlying mechanisms have been understudied to date. To address this issue, we comprehensively evaluated the cardiotoxicity of polystyrene nanoplastics (PS-NPs) in both healthy and pathological states. Briefly, mice were orally exposed to four different concentrations (0 mg/day, 0.1 mg/day, 0.5 mg/day, and 2.5 mg/day) of 100-nm PS-NPs for 6 weeks to assess their cardiotoxicity in a healthy state. Considering that individuals with underlying health conditions are more vulnerable to the adverse effects of pollution, we further investigated the cardiotoxic effects of PS-NPs on pathological states induced by isoprenaline. Results showed that PS-NPs induced cardiomyocyte apoptosis, cardiac fibrosis, and myocardial dysfunction in healthy mice and exacerbated cardiac remodeling in pathological states. RNA sequencing revealed that PS-NPs significantly upregulated homeodomain interacting protein kinase 2 (HIPK2) in the heart and activated the P53 and TGF-beta signaling pathways. Pharmacological inhibition of HIPK2 reduced P53 phosphorylation and inhibited the activation of the TGF-ß1/Smad3 pathway, which in turn decreased PS-NPs-induced cardiotoxicity. This study elucidated the potential mechanisms underlying PS-NPs-induced cardiotoxicity and underscored the importance of evaluating nanoplastics safety, particularly for individuals with pre-existing heart conditions.
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Cardiotoxicidad , Poliestirenos , Proteínas Serina-Treonina Quinasas , Proteína smad3 , Factor de Crecimiento Transformador beta1 , Proteína p53 Supresora de Tumor , Regulación hacia Arriba , Animales , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Crecimiento Transformador beta1/genética , Proteína smad3/metabolismo , Proteína smad3/genética , Cardiotoxicidad/etiología , Proteína p53 Supresora de Tumor/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Poliestirenos/toxicidad , Regulación hacia Arriba/efectos de los fármacos , Masculino , Transducción de Señal/efectos de los fármacos , Ratones , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/patología , Apoptosis/efectos de los fármacos , Ratones Endogámicos C57BL , Nanopartículas/toxicidad , Miocardio/metabolismo , Miocardio/patologíaRESUMEN
Photocatalysis is considered as an environmentally friendly and sustainable method as it can produce active species to degrade pollutants. However, its applications are hindered by the turbidity of pollutants and the requirements for continuous or repeated in situ irradiation. To avoid the need for continuous in situ irradiation in the photocatalytic process, herein we report the doping of Cu(II) ions into zinc gallate (ZnGa2O4) as traps to capture photo-generated electrons. In this way, long lifetime charge release and separation were effectively achieved for the persistent degradation of organic dyes in wastewater. The Cu(II) doped ZnGa2O4 (ZGC) nanoparticles with a small size about 7.7 nm synthesized via a hydrothermal method exhibited a persistent photocatalytic activity with continuous production of reactive oxygen species for at least 96 h without in situ irradiation due to its unique electronic structure and carrier transport path, and enabled to degrade 82.2 % of rhodamine B in 1 h. Further investigation revealed that the doped Cu(II) ions occupied the octahedral sites of ZGC and highly increased the persistent production and availability of active species for the persistent degradation of organic dyes under pre-illuminated conditions.
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Precise imaging-guided therapy of a pulmonary metastasis tumor is of great significance for tumor management and prognosis. Persistent luminescence nanoparticles (PLNPs) are promising probes due to their in situ excitation-free and low-background imaging characteristics. However, most of the PLNP-based probes cannot intelligently distinguish between normal and tumor tissues or balance the needs of targeted accumulation and rapid metabolism, resulting in false positive signals and potential side effects. Besides, the luminescence intensity of single-emissive PLNPs is affected by external factors. Herein, we report a self-evolving double-emissive PLNP-based nanoprobe ZGMC@ZGC-TAT for pulmonary metastatic tumor imaging and therapy. Acid-degradable green-emitting PLNPs (ZGMC) with good afterglow performance and therapeutic potential are synthesized by systematic optimization of dopants. Ultra-small red-emitting PLNPs (ZGC) are then prepared as imaging and reference probes. The two PLNPs are finally covalently coupled and further modified with a cell-penetrating peptide (TAT) to obtain ZGMC@ZGC-TAT. Dual emission ensures a stable luminescence ratio (I700/I537) independent of probe concentration, test voltage and time gate. ZGMC degrades and phosphorescence disappears in a tumor microenvironment (TME), resulting in an increase in I700/I537, thus enabling tumor-specific ratiometric imaging. Cu2+ and Mn2+ released by ZGMC degradation achieve GSH depletion and enhance CDT, effectively inhibiting tumor cell proliferation. Meanwhile, the size of ZGMC@ZGC-TAT decreases sharply, and the resulting ZGC-TAT further causes nuclear pyknosis and quickly clear metabolism. The developed ZGMC@ZGC-TAT turns non-targeted lung aggregation of nanomaterials into a unique advantage, and integrates TME-triggered phosphorescence and size self-evolution, and on-demand therapeutic functions, showing outstanding prospects in precise imaging and efficient treatment of pulmonary metastatic tumors.
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Neoplasias Pulmonares , Nanopartículas , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/tratamiento farmacológico , Nanopartículas/química , Animales , Humanos , Ratones , Imagen Óptica , Luminiscencia , Línea Celular Tumoral , Ratones Endogámicos BALB C , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/administración & dosificación , Ratones Desnudos , Péptidos de Penetración Celular/química , Péptidos de Penetración Celular/farmacologíaRESUMEN
Methamphetamine (METH) is a psychostimulant drug belonging to the amphetamine-type stimulant class, known to exert male reproductive toxicity. Recent studies suggest that METH can disrupt the gut microbiota. Furthermore, the gut-testis axis concept has gained attention due to the potential link between gut microbiome dysfunction and reproductive health. Nonetheless, the role of the gut microbiota in mediating the impact of METH on male reproductive toxicity remains unclear. In this study, we employed a mouse model exposed to escalating doses of METH to assess sperm quality, testicular pathology, and reproductive hormone levels. The fecal microbiota transplantation method was employed to investigate the effect of gut microbiota on male reproductive toxicity. Transcriptomic, metabolomic, and microbiological analyses were conducted to explore the damage mechanism to the male reproductive system caused by METH. We found that METH exposure led to hormonal disorders, decreased sperm quality, and changes in the gut microbiota and testicular metabolome in mice. Testicular RNA sequencing revealed enrichment of several Gene Ontology terms associated with reproductive processes, as well as PI3K-Akt signaling pathways. FMT conveyed similar reproductive damage from METH-treated mice to healthy recipient mice. The aforementioned findings suggest that the gut microbiota plays a substantial role in facilitating the reproductive toxicity caused by METH, thereby highlighting a prospective avenue for therapeutic intervention in the context of METH-induced infertility.
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Microbioma Gastrointestinal , Metanfetamina , Reproducción , Testículo , Animales , Metanfetamina/toxicidad , Masculino , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Testículo/efectos de los fármacos , Testículo/patología , Reproducción/efectos de los fármacos , Espermatozoides/efectos de los fármacos , Ratones Endogámicos C57BL , Estimulantes del Sistema Nervioso Central/toxicidad , Trasplante de Microbiota FecalRESUMEN
It is usually believed that doping with photosensitizers capable of generating singlet oxygen (1O2) plays a pivotal role in enhancing the afterglow performance of semiconducting polymer nanoparticles (SPNs). However, the effect of doping photosensitizer bearing electron-withdrawing groups has not been reported. Here we report the effect of doping with six photosensitizers possessing different electron-withdrawing groups on the afterglow performance of SPNs using poly[(9,9-di(2-ethylhexyl)-9H-fluo-rene-2,7-vinylene)-co-(1-methoxy-4-(2-ethylhexyloxy)-2,5-phenylenevinylene)] (PF-MEHPPV) as substrate. It was found that the afterglow performance of SPNs was significantly influenced by doping with photosensitizers bearing electron-withdrawing groups. For the doped photosensitizers with strong electron-withdrawing groups, the stronger the electron-withdrawing ability of the group, the worse of the afterglow performance of the SPN regardless of the 1O2 generation ability of the photosensitizer. When the doped photosensitizer exhibited weak or none electron-withdrawing effect, the 1O2 generation ability of the photosensitizer played a dominant role on the afterglow performance of the SPNs. This work deepens the understanding of the design and synthesis of SPNs with different afterglow properties.
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Organophosphorus flame retardants (OPFRs), such as 2-ethylhexyl diphenyl phosphate (EHDPHP), are ubiquitously used, leading to pervasive environmental contamination and human health risks. While associations between EHDPHP and health issues such as disruption of hormones, neurotoxic effects, and toxicity to reproduction have been recognized, exposure to EHDPHP during perinatal life and its implications for the intestinal health of dams and their pups have largely been unexplored. This study investigated the intestinal toxicity of EHDPHP and the potential for which inulin was effective. Dams were administered either an EHDPHP solution or a corn oil control from gestation day 7 (GD7) to postnatal day 21 (PND21), with inulin provided in their drinking water. Our results indicate that inulin supplementation mitigates damage to the intestinal epithelium caused by EHDPHP, restores mucus-secreting cells, suppresses intestinal hyperpermeability, and abates intestinal inflammation by curtailing lipopolysaccharide leakage through reshaping of the gut microbiota. A reduction in LPS levels concurrently inhibited the inflammation-associated TLR4/NF-κB pathway. In conclusion, inulin administration may ameliorate intestinal toxicity caused by EHDPHP in dams and pups by reshaping the gut microbiota and suppressing the LPS/TLR4/NF-κB pathway. These findings underscore the efficacy of inulin as a therapeutic agent for managing health risks linked to EHDPHP exposure.
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Compuestos de Bifenilo , Microbioma Gastrointestinal , Fosfatos , Embarazo , Femenino , Humanos , Fosfatos/farmacología , FN-kappa B , Lipopolisacáridos , Inulina/farmacología , Receptor Toll-Like 4/metabolismo , InflamaciónRESUMEN
Near-infrared (NIR)-emitting persistent luminescence nanoparticles (PLNPs) are ideal optical imaging contrast reagents characterized by autofluorescence-free optical imaging for their frontier applications in long-term bioimaging. Preparation of uniform small-sized PLNPs with excellent luminescence performance is crucial for biomedical applications, but challenging. Here, we report a facile magnesium doping strategy to achieve size-independent boost of NIR persistent luminescence in typical and most concerned ZnGa2O4:Cr3+ PLNPs. This strategy relies on the doping of Mg2+ ions that with similar size of Zn2+ ions in the host lattice matrix, and concomitant to the electron traps tailoring tuned by varying the feed ratio of Mg2+. The optimum Mg2+-doped PLNPs give a long afterglow time (signal-to-noise ratio (SNR) = 31.6 at 30 d) without changing the desirable uniform sub-10 nm size of the original nanocrystals. The appropriate increase of the depth and concentration of electron trap contribute jointly to the enhancement of lifetime (488 % longer, 20.57 s) and afterglow time for 700 nm persistent luminescence. Meanwhile, these PLNPs keep the original excellent rechargeability and promote over 60 times increase of SNR in renewable in vivo imaging. This simple strategy provides a basis for new opportunities to address the critical challenge of effective optical performance boost in small-sized PLNPs.
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BACKGROUND: Some studies have shown that gut microbiota may be associated with dementia. However, the causal effects between gut microbiota and different types of dementia and whether cytokines act as a mediator remain unclear. METHODS: Gut microbiota, cytokines, and five dementia types, including Alzheimer's disease (AD), frontotemporal dementia (FTD), dementia with Lewy body (DLB), vascular dementia (VD), and Parkinson's disease dementia (PDD) were identified from large-scale genome-wide association studies (GWAS) summary data. We used Mendelian randomization (MR) to investigate the causal relationships between gut microbiota, cytokines, and five types of dementia. Inverse variance weighting (IVW) was used as the main statistical method. In addition, we explored whether cytokines act as a mediating factor in the pathway from gut microbiota to dementia. RESULTS: There were 20 positive and 16 negative causal effects between genetic liability in the gut microbiota and dementia. Also, there were five positive and four negative causal effects between cytokines and dementias. Cytokines did not act as mediating factors. CONCLUSIONS: Gut microbiota and cytokines were causally associated with five types of dementia, and cytokines seemed not to be the mediating factors in the pathway from gut microbiota to dementia.
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Enfermedad de Alzheimer , Demencia Frontotemporal , Microbioma Gastrointestinal , Enfermedad de Parkinson , Humanos , Microbioma Gastrointestinal/genética , Citocinas/genética , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización MendelianaRESUMEN
Prenatal exposure to methamphetamine (METH) is an issue of global concern due to its adverse effects on offspring, particularly its impact on liver health, an area still not fully understood. Inulin, a recognized prebiotic, is thought to potentially ameliorate these developmental disorders and toxic injuries in progeny. To investigate the effects of prenatal METH exposure on the liver and the role of gut microbiota, we established a murine model, the subjects of which were exposed to METH prenatally and subsequently treated with inulin. Our findings indicate that prenatal METH exposure causes liver damage in offspring, as evidenced by a decreased liver index, histopathological changes, diminished glycogen synthesis, hepatic dysfunction, and alterations in mRNA profiles. Furthermore, it impairs the antioxidant system and induces oxidative stress, possibly due to changes in cecal microbiota and dysregulation of bile acid homeostasis. However, maternal inulin supplementation appears to restore the gut microbiota in offspring and mitigate the hepatotoxic effects induced by prenatal METH exposure. Our study provides definitive evidence of METH's transgenerational hepatotoxicity and suggests that maternal inulin supplementation could be an effective preventive strategy.
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Enfermedad Hepática Inducida por Sustancias y Drogas , Microbioma Gastrointestinal , Metanfetamina , Efectos Tardíos de la Exposición Prenatal , Embarazo , Femenino , Ratones , Animales , Humanos , Metanfetamina/toxicidad , Inulina/farmacología , Suplementos Dietéticos , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & controlRESUMEN
Covalent organic frameworks (COFs) have promising applications in enhanced phototherapy. However, COFs that can sustainably play a role in phototherapy without continuous irradiation are extremely scarce. Herein, we report the fabrication of porphyrin-anthracene multifunctional COFs (Por-DPA) for sustainable photosterilization and bacterial-infected wound healing. A porphyrin photosensitizer, as one of the monomers, was used to provide photothermal and photodynamic activities under irradiation. An anthracene derivative, a good chemical source of singlet oxygen (1O2), was selected as another monomer to capture 1O2 and release it continuously via cycloreversion in the dark. The prepared Por-DPA COF prevents the self-aggregation quenching of the photosensitizer and thermal damage caused by continuous exposure to external light sources. Besides, Por-DPA exhibits good photothermal conversion performance and efficient 1O2 production capacity through dual pathways of photosensitization and cycloreversion. The developed sustainable photosterilization platform not only has good bactericidal effects on Escherichia coli and Staphylococcus aureus, but also promotes wound healing without obvious side effects, and is expected to be a novel efficient bactericide.
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Estructuras Metalorgánicas , Porfirinas , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Estructuras Metalorgánicas/farmacología , Estructuras Metalorgánicas/química , Porfirinas/farmacología , Porfirinas/química , Fototerapia , Oxígeno Singlete/metabolismoRESUMEN
Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy that presents with sudden onset of chest pain and dyspneic and cardiac dysfunction as a result of extreme physical or emotional stress. The sigma-1 receptor (Sigmar1) is a ligand-dependent molecular chaperone that is postulated to be involved in various processes related to cardiovascular disease. However, the role of Sigmar1 in TTS remains unresolved. In this study, we established a mouse model of TTS using wild-type and Sigmar1 knockout mice to investigate the involvement of Sigmar1 in TTS development. Our results revealed that Sigmar1 knockout exacerbated cardiac dysfunction, with a noticeable decrease in ejection fraction (EF) and fractional shortening (FS) compared to the wild-type model. In terms of the gut microbiome, we observed regulation of Firmicutes and Bacteroidetes ratios; suppression of probiotic Lactobacillus growth; and a rise in pathogenic bacterial species, such as Colidextribacter. Metabolomic and transcriptomic analyses further suggested that Sigmar1 plays a role in regulating tryptophan metabolism and several signaling pathways, including MAPK, HIF-1, calcium signaling, and apoptosis pathways, which may be crucial in TTS pathogenesis. These findings offer valuable insight into the function of Sigmar1 in TTS, and this receptor may represent a promising therapeutic target for TTS.
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Introduction: Heart failure (HF) is usually the end stage of the continuum of various cardiovascular diseases. However, the mechanism underlying the progression and development of HF remains poorly understood. The sigma-1 receptor (Sigmar1) is a non-opioid transmembrane receptor implicated in many diseases, including HF. However, the role of Sigmar1 in HF has not been fully elucidated. Methods: In this study, we used isoproterenol (ISO) to induce HF in wild-type (WT) and Sigmar1 knockout (Sigmar1-/-) mice. Multi-omic analysis, including microbiomics, metabolomics and transcriptomics, was employed to comprehensively evaluate the role of Sigmar1 in HF. Results: Compared with the WT-ISO group, Sigmar1-/- aggravated ISO-induced HF, including left ventricular systolic dysfunction and ventricular remodeling. Moreover, Sigmar1-/- exacerbated ISO-induced gut microbiota dysbiosis, which was demonstrated by the lower abundance of probiotics g_Akkermansia and g_norank_f_Muribaculaceae, and higher abundance of pathogenic g_norank_f_Oscillospiraceae and Allobaculum. Furthermore, differential metabolites among WT-Control, WT-ISO and Sigmar-/--ISO groups were mainly enriched in bile secretion, tryptophan metabolism and phenylalanine metabolism, which presented a close association with microbial dysbiosis. Corresponding with the exacerbation of the microbiome, the inflammation-related NOD-like receptor signaling pathway, NF-kappa B signaling pathway and TNF signaling pathway were activated in the heart tissues. Conclusion: Taken together, this study provides evidence that a Sigmar1 knockout disturbs the gut microbiota and remodels the serum metabolome, which may exacerbate HF by stimulating heart inflammation.
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Organophosphorus flame retardants (OPFRs), including 2-ethylhexyl diphenyl phosphate (EHDPHP), are prevalent in everyday life due to their broad usage in fields such as healthcare, electronics, industry, and sports. These compounds, added to polymers through physical mixing, can leach into the environment, posing a risk to humans through direct contact or the food chain. Despite known associations with health issues like endocrine disruption, neurotoxicity, and reproductive toxicity, the implications of perinatal EHDPHP exposure on both mothers and offspring are still unclear. This study aimed to investigate the neuroinflammatory effects of EHDPHP and the potential mitigating role of inulin. Pregnant C57 mice were administered either a corn oil control or an EHDPHP solution (300 µg/kg bw/d) from gestation day 7 (GD7) to postnatal day 21 (PND21). Concurrently, mice were provided either regular drinking water or water supplemented with 1% inulin. We found that EHDPHP significantly increased the serum levels of IL-1ß, IL-6, and MDA, but decreased SOD levels in both mothers and pups. These effects were reversed by inulin supplementation. RNA-sequencing revealed that EHDPHP induced inflammation and oxidative stress through the TLR4/NF-κB pathway, which was mitigated by inulin. In conclusion, inulin ameliorated EHDPHP-induced neuroinflammation and oxidative stress in both mothers and offspring, highlighting its potential therapeutic role.
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Retardadores de Llama , Fosfatos , Embarazo , Ratones , Humanos , Femenino , Animales , Organofosfatos/toxicidad , Inulina , Enfermedades Neuroinflamatorias , Estrés Oxidativo , Retardadores de Llama/toxicidadRESUMEN
We aimed to examine impacts and functional mechanism of circular RNA forkhead box N2 (FOXN2) in tacrolimus (TAC)- and dexamethasone (Dex)-induced lipid metabolism disorders. RNA level and protein contents in TAC, Dex, or combined TAC- plus Dex-treated patients and Huh-7 cells were measured utilizing quantitative real-time (qRT)-PCR and western blotting assays measured the formation of lipid droplet. Total cholesterol (TC) and triglyceride (TG) levels were determined using corresponding commercial kits and Oil red O staining. RNA immunoprecipitation and RNA pull-down verified the binding relationship among circFOXN2, polypyrimidine tract binding protein 1 (PTBP1) and fatty acid synthase (FASN). Male C57BL/6 mice were used to establish a dyslipidemia mouse model to validate the discoveries at the cellular level. Dex treatment significantly promoted TAC-mediated increase of TC and TG in serum samples and Huh-7 cells. Moreover, circFOXN2 was reduced but FASN was elevated in TAC-treated Huh-7 cells, and these expression trends were markedly enhanced by Dex cotreatment. Overexpression of circFOXN2 could reverse the accumulation of TC and TG and the upregulation of FASN and sterol regulatory element binding transcription factor 2 (SREBP2) mediated by Dex and TAC cotreatment. Mechanistically, circFOXN2 reduced FASN mRNA stability by recruiting PTBP1. The protective roles of circFOXN2 overexpression on lipid metabolism disorders were weakened by FASN overexpression. In vivo finding also disclosed that circFOXN2 greatly alleviated the dysregulation of lipid metabolism triggered by TAC plus Dex. CircFOXN2 alleviated the dysregulation of lipid metabolism induced by the combination of TAC and Dex by modulating the PTBP1/FASN axis.NEW & NOTEWORTHY Collectively, our experiments revealed for the first time that circFOXN2 alleviated the Dex- and TAC-induced dysregulation of lipid metabolism by regulating the PTBP1/FASN axis. These findings suggested that circFOXN2 and FASN might be candidate targets for the treatment of Dex- and TAC-induced metabolic disorders.
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Dislipidemias , Trasplante de Hígado , Ratones , Animales , Masculino , Glucocorticoides , Tacrolimus/metabolismo , Ratones Endogámicos C57BL , Ácido Graso Sintasas , Dislipidemias/inducido químicamente , Dislipidemias/tratamiento farmacológico , Dislipidemias/genética , ARN/metabolismo , Estabilidad del ARN , Hígado/metabolismoRESUMEN
Coating mesoporous drug carriers on the surface of persistent luminescence nanoparticles (PLNPs) not only allows continuous luminous imaging without spontaneous fluorescence interference, but also provides drug release guidance. However, in most cases, the encapsulation of the drug-loaded shells significantly reduces the luminescence of PLNPs, which is unfavorable for bioimaging. In addition, conventional drug-loaded shells alone, such as silica shells, have difficulty in achieving responsive fast drug release. Herein, we report the fabrication of mesoporous polyacrylic acid (PAA)/calcium phosphate (CaP) shell-coated PLNPs (PLNPs@PAA/CaP) for improved afterglow bioimaging and drug delivery. The encapsulation of the PAA/CaP shell effectively prolonged the decay time and enhanced the sustained luminescence of PLNPs by about three times due to the passivation of the surface defects of PLNPs by the shell, and the energy transfer between the shell and PLNPs. Meanwhile, the mesoporous structure and negative charge of the PAA/CaP shells enabled the prepared PLNPs@PAA/CaP to carry the positively charged drug doxycycline hydrochloride efficiently. Under the acidic conditions of bacterial infection, the degradation of PAA/CaP shells and the ionization of PAA enabled fast drug release for effective killing of bacteria at the infection site. The excellent persistent luminescence properties, outstanding biocompatibility, and rapid responsive release feature make the prepared PLNPs@PAA/CaP a promising nanoplatform for diagnostic and therapeutic applications.
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Infecciones Bacterianas , Nanopartículas , Humanos , Luminiscencia , Nanopartículas/química , Fosfatos de CalcioRESUMEN
Polystyrene microplastics (PS-MPs) have emerged as a concerning pollutant in modern society due to their widespread production and usage. Despite ongoing research efforts, the impact of PS-MPs on mammalian behavior and the mechanisms driving these effects remain incompletely elucidated. Consequently, effective strategies for prevention have yet to be developed. To fill these gaps, C57BL/6 mice were orally administered with 5 µm PS-MPs for 28 consecutive days in this study. The open-field test and the elevated plus-maze test were performed to evaluate the anxiety-like behavior, 16S rRNA sequencing and untargeted metabolomics analysis were used to detect the changes of gut microbiota and serum metabolites. Our results indicated that PS-MPs exposure activated hippocampal inflammation and induced anxiety-like behavior in mice. Meanwhile, PS-MPs disturbed the gut microbiota, impaired the intestinal barrier, and aroused peripheral inflammation. Specifically, PS-MPs increased the abundance of pathogenic microbiota Tuzzerella, while lowered the abundance of probiotics Faecalibaculum and Akkermansia. Interestingly, eliminating the gut microbiota protected against the deleterious effects of PS-MPs on intestinal barrier integrity, reduced the levels of peripheral inflammatory cytokines, and ameliorated anxiety-like behavior. Additionally, green tea's primary bioactive constituent, epigallocatechin-3-gallate (EGCG), optimized gut microbial composition, improved intestinal barrier function, reduced peripheral inflammation, and exerted anti-anxiety effects by inhibiting the hippocampal TLR4/MyD88/NF-κB signaling cascade. EGCG also remodeled serum metabolism, especially modulated purine metabolism. These findings suggested that gut microbiota participates in PS-MPs-induced anxiety-like behavior by modulating the gut-brain axis, and that EGCG could serve as a potential preventive strategy.
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Microbioma Gastrointestinal , Animales , Ratones , Ratones Endogámicos C57BL , Microplásticos , Plásticos , Poliestirenos/toxicidad , ARN Ribosómico 16S , Homeostasis , Inflamación/inducido químicamente , MamíferosRESUMEN
Introduction: Burn injury has been shown to lead to changes in the composition of the gut microbiome and cause other damage in patients. However, little is known about how the gut microbial community evolves in individuals who have recovered from burn injury. Methods: In this study, we established a model of deep partial-thickness burn in mice and collected fecal samples at eight time points (pre-burn, 1, 3, 5, 7, 14, 21, and 28 days post-burn) for 16S rRNA amplification and high-throughput sequencing. Results: The results of the sequencing were analyzed using measures of alpha diversity, and beta diversity and taxonomy. We observed that the richness of the gut microbiome declined from day 7 post-burn and that the principal component and microbial community structure varied over time. On day 28 after the burn, the microbiome composition largely returned to the pre-burn level, although day 5 was a turning point for change. Some probiotics, such as the Lachnospiraceae_NK4A136_group, decreased in composition after the burn but were restored in the later recovery period. In contrast, Proteobacteria showed an opposite trend, which is known to include potential pathogenic bacteria. Conclusion: These findings demonstrate gut microbial dysbiosis after burn injury and provide new insights into the burn-related dysbiosis of the gut microbiome and strategies for improving the treatment of burn injury from the perspective of the microbiota.
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Introduction: Depression is a common mental disorder that affects approximately 350 million people worldwide. Much remains unknown about the molecular mechanisms underlying this complex disorder. Sigma-1 receptor (Sig-1R) is expressed at high levels in the central nervous system. Increasing evidence has demonstrated a close association between the Sig-1R and depression. Recently, research has suggested that the gut microbiota may play a crucial role in the development of depression. Methods: Male Sig-1R knockout (Sig-1R KO) and wild-type (WT) mice were used for this study. All transgenic mice were of a pure C57BL/6J background. Mice received a daily gavage of vancomycin (100 mg/kg), neomycin sulfate (200 mg/kg), metronidazole (200 mg/kg), and ampicillin (200 mg/kg) for one week to deplete gut microbiota. Fecal microbiota transplantation (FMT) was conducted to assess the effects of gut microbiota. Depression-like behaviors was evaluated by tail suspension test (TST), forced swimming test (FST) and sucrose preference test (SPT). Gut microbiota was analyzed by 16s rRNA and hippocampal transcriptome changes were assessed by RNA-seq. Results: We found that Sig-1R knockout induced depression-like behaviors in mice, including a significant reduction in immobility time and an increase in latency to immobility in the FST and TST, which was reversed upon clearance of gut microbiota with antibiotic treatment. Sig-1R knockout significantly altered the composition of the gut microbiota. At the genus level, the abundance of Alistipes, Alloprevotella, and Lleibacterium decreased significantly. Gut microbiota dysfunction and depression-like phenotypes in Sig-1R knockout mice could be reproduced through FMT experiments. Additionally, hippocampal RNA sequencing identified multiple KEGG pathways that are associated with depression. We also discovered that the cAMP/CREB/BDNF signaling pathway is inhibited in the Sig-1R KO group along with lower expression of neurotrophic factors including CTNF, TGF-α and NGF. Fecal bacteria transplantation from Sig-1R KO mice also inhibited cAMP/CREB/BDNF signaling pathway. Discussion: In our study, we found that the gut-brain axis may be a potential mechanism through which Sig-1R regulates depression-like behaviors. Our study provides new insights into the mechanisms by which Sig-1R regulates depression and further supports the concept of the gut-brain axis.
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Methamphetamine (METH) is a psychotropic drug known to cause cardiotoxicity. The gut-heart axis is emerging as an important pathway linking gut microbiota to cardiovascular disease, but the precise association between METH-induced cardiotoxicity and gut microbiota has yet to be elucidated. In this study, we established an escalating dose-multiple METH administration model in male BALB/c mice, examined cardiac injury and gut microbiota, and investigated the contribution of gut microbiota to cardiotoxicity induced by METH. Additionally, we treated mice with antibiotics and fecal microbiota transplantation (FMT) to assess the impact of gut microbiota on cardiotoxicity. Our results showed that METH exposure altered the p53 and PI3K/Akt signaling pathways and modulated the apoptosis pathway in heart tissue, accompanied by elevated levels of Bax/BCL-2 expression and cleaved caspase-3 proteins. METH exposure increased the diversity and richness of gut microbiota, and significantly changed the microbial community composition, accompanied by elevated abundance of Lactobacillus, Bifidobacterium, and decreased abundance of Bacteroides, norank_f_Muribaculaceae and Alistipes. Eliminating gut microbiota by antibiotics treatment alleviated METH-induced cardiotoxicity, while FMT treatment transferred similar cardiac injury manifestations from METH-exposed mice to healthy recipient mice. Our study unveils the crucial involvement of gut microbiota in the development of cardiotoxicity induced by METH and provides potential strategies for treating cardiac complications caused by METH.
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Microbioma Gastrointestinal , Metanfetamina , Masculino , Ratones , Animales , Metanfetamina/toxicidad , Cardiotoxicidad , Fosfatidilinositol 3-Quinasas , AntibacterianosRESUMEN
Accurate and sensitive detection of ochratoxin A (OTA) is highly necessary due to its high carcinogenicity, teratogenicity and mutagenicity. Herein, we reported an exogenous interference and autofluorescence-free ratiometric aptasensor based on dual-colored persistent luminescent nanoparticles for precise detection of OTA. Green-emitting ZnGeO:Mn bonded with OTA aptamer and BHQ1-modified complementary base was acted as detection and specific recognition probe (ZGM@BHQ1). Quaternary ammonium modified ZnGaGeO:Cr with red emission was employed as reference probe and further bonded to ZGM@BHQ1 through electrostatic interaction to construct the ratiometric aptasensor. The developed ratiometric aptasensor was free from real-time excitation, external interference and autofluorescence and gave low detection limit of 3.4 pg mL-1, wide linearity in the range of 0.01-50 ng mL-1 and high precision of 3.1 % (11 replicate determinations, at 1 ng mL-1 level). The applicability of the aptasensor was successfully demonstrated by analyzing OTA in in grain samples with recoveries of 97.6 %-105.2 %.