Compared with conventional tumor photothermal therapy (PTT), mild‐temperature PTT brings less damage to normal tissues, but also tumor thermoresistance, introduced by the overexpressed heat shock ...protein (HSP). A high dose of HSP inhibitor during mild‐temperature PTT might lead to toxic side effects. Glucose oxidase (GOx) consumes glucose, leading to adenosine triphosphate supply restriction and consequent HSP inhibition. Therefore, a combinational use of an HSP inhibitor and GOx not only enhances mild‐temperature PTT but also minimizes the toxicity of the inhibitor. However, a GOx and HSP inhibitor‐encapsulating nanostructure, designed for enhancing its mild‐temperature tumor PTT efficiency, has not been reported. Thermosensitive GOx/indocyanine green/gambogic acid (GA) liposomes (GOIGLs) are reported to enhance the efficiency of mild‐temperature PTT of tumors via synergistic inhibition of tumor HSP by the released GA and GOx, together with another enzyme‐enhanced phototherapy effect. In vitro and in vivo results indicate that this strategy of tumor starvation and phototherapy significantly enhances mild‐temperature tumor PTT efficiency. This strategy could inspire people to design more delicate platforms combining mild‐temperature PTT with other therapeutic methods for more efficient cancer treatment.
Thermosensitive liposomes made of DPPC and DSPE‐PEG2000 encapsulating GOx, ICG, and GA are presented. This system is used for synergistic starvation therapy, EEPT, and enhanced mild‐temperature PTT against tumors.
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-1β, 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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•Perinatal exposure to EHDPHP led to neuroinflammation and oxidative stress in dams and pups.•EHDPHP upregulated the expressions of inflammation and oxidative stress related biomarkers.•Inulin attenuated EHDPHP-associated oxidative stress and neuroinflammation in both dams and pups.
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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•Methamphetamine (METH) exposure induced reproductive toxicity in male mice.•METH exposure caused changes in the gut microbiome and compromised the integrity of the intestinal barrier.•METH exposure altered the testicular transcriptome and metabolic expression profiles.•Fecal microbiota transplantation conveyed similar reproductive damage from METH-treated mice to healthy recipient mice.
In this work, we prepared quaternized carbon dots (CDs) with simultaneous antibacterial and bacterial differentiation capabilities using a simple carboxyl–amine reaction between lauryl betaine and ...amine-functionalized CDs. The obtained quaternized CDs have several fascinating properties/abilities: (1) A long fluorescence emission wavelength ensures the exceptional bacterial imaging capability, including the super-resolution imaging ability; (2) the polarity-sensitive fluorescence emission property leads to significantly enhanced fluorescence when the quaternized CDs interact with bacteria; (3) the presence of both hydrophobic hydrocarbon chains and positively charged quaternary ammonium groups makes the CDs selectively attach to Gram-positive bacteria, realizing the bacterial differentiation; (4) excellent antimicrobial activity is seen against Gram-positive bacteria with a minimum inhibitory concentration of 8 μg/mL for Staphylococcus aureus. Besides, the quaternized CDs are highly stable in various aqueous solutions and exhibit negligible cytotoxicity, suggesting that they hold great promise for clinical applications. Compared to the traditional Gram staining method, the selective Gram-positive bacterial imaging achieved by the quaternized CDs provides a much simpler and faster method for bacterial differentiation. In summary, by combining selective Gram-positive bacterial recognition, super-resolution imaging, and exceptional antibacterial activity into a single system, the quaternized CDs represent a novel kind of metal-free nanoparticle-based antibiotics for antibacterial application and a new type of reagent for efficient bacterial differentiation.
Pulmonary fibrosis (PF) is a senescence‐associated disease with poor prognosis. Currently, there is no effective therapeutic strategy for preventing and treating the disease process. Mounting ...evidence suggests that arachidonic acid (ARA) metabolites are involved in the pathogenesis of various fibrosis. However, the relationship between the metabolism of ARA and PF is still elusive. In this study, we observed a disorder in the cyclooxygenase‐2/cytochrome P450 (COX‐2/CYP) metabolism of ARA in the lungs of PF mice induced by bleomycin (BLM). Therefore, we aimed to explore the role of COX‐2/CYP‐derived ARA metabolic disorders in PF. PTUPB, a dual COX‐2 and soluble epoxide hydrolase (sEH) inhibitor, was used to restore the balance of COX‐2/CYP metabolism. sEH is an enzyme hydrolyzing epoxyeicosatrienoic acids derived from ARA by CYP. We found that PTUPB alleviated the pathological changes in lung tissue and collagen deposition, as well as reduced senescence marker molecules (p16Ink4a and p53‐p21Waf1/Cip1) in the lungs of mice treated by BLM. In vitro, we found that PTUPB pretreatment remarkably reduced the expression of senescence‐related molecules in the alveolar epithelial cells (AECs) induced by BLM. In conclusion, our study supports the notion that the COX‐2/CYP‐derived ARA metabolic disorders may be a potential therapeutic target for PF via inhibiting the cellular senescence in AECs.
Here, we observed a disorder in the cyclooxygenase‐2/cytochrome P450 (COX‐2/CYP) metabolism of arachidonic acid in the lungs of mice with pulmonary fibrosis (PF) induced by bleomycin. PTUPB, a dual COX‐2 and soluble epoxide hydrolase inhibitor, was used to restore the balance of COX‐2/CYP metabolism. Our findings showed that PTUPB alleviated bleomycin‐induced PF via inhibiting the cellular senescence in alveolar epithelial cells, indicating a potential therapeutic target for PF.
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•METH induced hepatotoxicity and enterotoxicity.•Propionate, rather than acetate or butyrate, ameliorates METH-induced hepatotoxicity and enterotoxicity.•Propionate supplementation ...ameliorates intestinal permeability and suppressed the LPS-TLR4-NF-κB pathway, ultimately improving the dysfunction of METH-induced liver and colon.
The abuse of methamphetamine (METH) has emerged as a major public health concern, causing liver and intestinal damage upon exposure. Short chain fatty acids (SCFAs) produced by dietary fiber, including acetate, propionate, and butyrate, have been reported to alleviate various liver toxicities and exhibit distinct physiological effects. However, the role of SCFAs in mitigating METH-induced liver and intestinal damage remains unexplored. This study is designed to elucidate this potential therapeutic effect, by administering either METH or saline via injection to BALB/c mice, supplemented with acetate, propionate, or butyrate in their drinking water. We discovered that propionate demonstrated the most significant effect in mitigating pathological changes, glycogen storage, inflammation, and hepatic function impairments in the liver induced by METH. Propionate supplementation attenuated damage to the intestinal epithelial barrier, restored mucus-secreting cells, inhibited intestinal inflammation, suppressed intestinal hyperpermeability, and reduced lipopolysaccharide (LPS) leakage caused by METH. With the alleviation of LPS endotoxemia, the TLR4/MyD88/NF-κB pathway associated with inflammation in the liver and colon was inhibited. In conclusion, propionate supplementation ameliorated hepatic and colon dysfunction and inflammation resulting from METH exposure through suppression of the TLR4/MyD88/NF-κB pathway.
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.
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.
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.
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.
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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•PS-MPs stimulated hippocampal inflammation and induced anxiety-like behavior in mice.•PS-MPs disturbed gut microbiota and impaired intestinal barrier function.•PS-MPs exposure increased serum LPS level and peripheral inflammation.•Eliminating gut microbiota protected against impairment of the gut barrier by PS-MPs.•EGCG optimized gut microbiota and serum metabolism, improved anxiety-like behavior.
With the emergence of antibiotic resistance, developing new antibiotics and therapies for combating bacterial infections is urgently needed. Herein, a series of quaternized fluorescent silicon ...nanoparticles (SiNPs) are facilely prepared by the covalent reaction between amine‐functionalized SiNPs and carboxyl‐containing N‐alkyl betaines. It is found that the bactericidal efficacy of these quaternized SiNPs increases with the length of the N‐alkyl chain, and SiNPs conjugated with N,N‐dimethyl‐N‐octadecylbetaine (BS‐18), abbreviated as SiNPs‐C18, show the best antibacterial effect, whose minimum inhibitory concentrations for Gram‐positive bacteria are 1–2 μg mL−1. In vivo tests further confirm that SiNPs‐C18 have excellent antibacterial efficacy and greatly reduce bacterial load in the infectious sites. The SiNPs‐C18 exhibit low cytotoxicity toward mammalian cells (including normal liver and lung cells, red blood cells, and macrophages), enabling them to be useful for clinical applications. Besides, the quaternized SiNPs exhibit polarity‐dependent fluorescence emission property and can selectively image Gram‐positive bacteria, thereby providing a simple method to successfully differentiate Gram‐positive and Gram‐negative bacteria. The present work represents the first example that successfully turns fluorescent SiNPs into metal‐free NP‐based antibiotics with simultaneous bacterial imaging and killing capability, which broadens the applications of fluorescent SiNPs and advances the development of novel antibacterial agents.
A simple and efficient method is developed based on fluorescent quaternized silicon nanoparticles (SiNPs) to meet the increasing demands of bacterial differentiation and metal‐free NP‐based antibiotics. The quaternized SiNPs with polarity‐dependent fluorescence emission possess superb selectivity to image and kill Gram‐positive bacteria over Gram‐negative ones. The low cytotoxicity of quaternized SiNPs enables them for future clinical application.
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