Polystyrene nanoparticles enhance the adverse effects of di-(2-ethylhexyl) phthalate on male reproductive system in mice.

Coexposure of nanoplastics (NPs) with other pollutants adsorbed from the surroundings has received extensive attention. Currently, the combined effects of NPs and plasticizers remain unclear. Di-(2-ethylhexyl) phthalate (DEHP) is a commonly used plasticizer that has raised much concern owing to its ubiquitous pollution and endocrine-disrupting potential. This study aimed to investigate the toxic effects on the male reproductive system upon coexposure to NPs and DEHP. The C57BL/6J mice were orally administrated with polystyrene nanoparticles (PSNPs), DEHP or both for 35 days to evaluate their effects on sperm quality, histology of testes and epididymides, testicular transcriptomic characteristics as well as expression of some important genes in the epididymides. The low-dose PSNPs used here did not induce significant changes in sperm quality, while DEHP alone or cotreatment with DEHP and PSNPs caused notable impairment, mainly manifesting as decreased sperm quality and aberrant structure of the testis and epididymis. Moreover, enhanced toxic effects were found in the cotreatment group when compared with the individual DEHP treatment group, as manifested by more obvious alterations in the sperm parameters as well as histological changes in the testis and epididymis. Testicular transcriptomic analysis revealed differential regulation of genes involved in immune response, cytoplasmic pattern recognition receptor signaling pathways, protein ubiquitination, oxidative stress, necrotic cell death, ATP synthesis and the cellular respiratory chain. RT-qPCR verified that the expression patterns of Cenpb, Crisp1 and Mars were changed in testes, and genes relevant to epididymal function including Aqp9 and Octn2 were downregulated in epididymides, particularly in the cotreatment group. Collectively, our results emphasize that DEHP at an environmentally relevant dose can induce male reproductive toxicity, and PSNPs may aggravate the toxic effects.

A natural biological adhesive from snail mucus for wound repair.

The discovery of natural adhesion phenomena and mechanisms has advanced the development of a new generation of tissue adhesives in recent decades. In this study, we develop a natural biological adhesive from snail mucus gel, which consists a network of positively charged protein and polyanionic glycosaminoglycan. The malleable bulk adhesive matrix can adhere to wet tissue through multiple interactions. The biomaterial exhibits excellent haemostatic activity, biocompatibility and biodegradability, and it is effective in accelerating the healing of full-thickness skin wounds in both normal and diabetic male rats. Further mechanistic study shows it effectively promotes the polarization of macrophages towards the anti-inflammatory phenotype, alleviates inflammation in chronic wounds, and significantly improves epithelial regeneration and angiogenesis. Its abundant heparin-like glycosaminoglycan component is the main active ingredient. These findings provide theoretical and material insights into bio-inspired tissue adhesives and bioengineered scaffold designs.

Results of a 30-day safety assessment in young mice orally exposed to polystyrene nanoparticles.

Polystyrene nanoparticles (PSNPs) are a newly emerging pollutant in the natural environment. However, due to the lack of sufficient toxicological studies in mammals, the potential effects of PSNPs on human health remain largely undefined. Therefore, in this study, young mice aged four weeks old were subjected to oral administration of 0, 0.2, 1, or 10 mg/kg PSNPs for 30 days. Our results demonstrated for the first time that oral exposure to PSNPs affected the expressions of mucus secretion-related genes and altered the community composition of intestinal microbiota, although this treatment did not cause behavioral impairments in young mice. No significant alterations in inflammatory or oxidative stress-related indicators were observed in the liver, lung, intestine, cortex or serum of PSNPs-treated animals. Moreover, exposure to PSNPs did not cause pathological changes in the liver, lung, or cortex tissues. Notably, although oral administration of PSNPs did not produce obvious toxic effects in the major organs of young mice, the possible toxicity of PSNPs remains unresolved and it may depend on the dose, exposure route and species. The potential hazardous effects of PSNPs still need to be systematically assessed, especially for children who are susceptible to exposure to nanoparticles.

Polystyrene nanoparticles aggravate the adverse effects of di-(2-ethylhexyl) phthalate on different segments of intestine in mice.

Emerging evidence indicates that nanoplastics (NPs) can transport organic pollutants such as di-(2-ethylhexyl) phthalate (DEHP) into organisms and induce adverse health effects. Nevertheless, the toxic effects of NPs combined with DEHP on mammalian intestine are still unclear. In this study, the C57BL6J mice were exposed to polystyrene nanoparticles (PSNPs), DEHP or them both for 30 days to determine their effects on different segments of intestine and the gut microbiota. As a result, DEHP alone or co-exposure to DEHP and PSNPs induced histological damages in all intestinal parts, mainly manifested as the decreased villus lengths, increased crypt depths in the duodenum, jejunum and ileum and decreased villus counts accompanied with decreased epithelial area in the colon. Moreover, decreased mucus coverage, down-regulated Muc2 expression levels as well as the broken tight junctions were observed in intestinal epithelium of mice, particularly obvious in the co-treatment groups. In general, as manifested by greater alterations in most of the parameters mentioned above, simultaneously exposed to PSNPs and DEHP seemed to induce enhanced toxic effects on intestine of mouse when compared with DEHP alone. Furthermore, the altered community composition of gut microbiota might at least partially contribute to these abnormalities. Overall, our results highlight the aggravated toxicity on different segments of intestine in mammalians due to co-exposure of PSNPs and DEHP, and these findings will provide valuable insights into the health risk of NPs and plastic additives.

Repression of autophagy leads to acrosome biogenesis disruption caused by a sub-chronic oral administration of polystyrene nanoparticles.

As a new widespread contaminant, nanoplastics (NPs) pose a potential risk to human health. Nevertheless, the adverse effects of NPs on the male reproductive system are poorly understood. In this study, we aimed to determine the effects of polystyrene nanoplastics (PS-NPs) (50 nm) on sperm quality, with a focus on the acrosome defects. After 35 days of intragastric administration, sperm quality was decreased and testicular structures were impaired in mice exposed to PS-NPs in both the medium (1.0 mg/kg) and high dose (10 mg/kg) groups. No significant changes were observed in the low dose (0.2 mg/kg) group. Meanwhile, acrosome parameters including acrosome integrity and acrosome reaction were decreased after the administration of PS-NPs. These findings were consistent with the disruption of acrosome biogenesis, as identified by the changed testicular ultrastructure. Additionally, the findings were further validated using seven marker genes (Gba2, Pick1, Gopc, Hrb, Zpbp1, Spaca1 and Dpy19l2) essential for acrosome formation, which showed that two of these genes (Gopc and Dpy19l2) were significantly down-regulated. Moreover, repressed autophagy was observed in the testes of PS-NPs-exposed mice based on autophagy-related protein expression. This phenomenon was further verified in GC-2spd cells treated with PS-NPs (50 µg/mL, 100 µg/mL, 200 µg/mL for 24 h). The potential role of autophagy in such acrosome defects was explored by using the autophagy inhibitor 3-methyladenine (3-MA), autophagy activator rapamycin or beclin-1 siRNA. The results showed that Golgi-associated vesicle disorganization was exacerbated with the 3-MA and beclin-1 siRNA pretreatments, but decreased with the rapamycin pretreatment, and the expression of GOPC and DPY19L2 was also altered. These results indicated that autophagy might be involved in the PS-NPs-induced acrosome lesions based on the regulation of two key acrosome-formation proteins, GOPC and DPY19L2. Altogether, our results will provide new insights into the PS-NPs-induced male reproductive impairment.

Developing protein arginine methyltransferase 1 (PRMT1) inhibitor TC-E-5003 as an antitumor drug using INEI drug delivery systems.

Injectable implants with the ability to form in situ are one of the most promising carriers for the delivery of chemotherapeutic drugs to tumor sites. We have reported a novel injectable in situ-forming implant system composed of n-butyl-2-cyanoacrylate (NBCA), ethyl oleate, along with the sol-gel phase transition. The chemotherapeutic drug-loaded injectable NBCA ethyl oleate implant (INEI) exhibited excellent therapeutic efficacy for local chemotherapy. Herein, we utilize this INEI to carry N, N'-(Sulfonyldi-4,1-phenylene)bis(2-chloroacetamide) (TE-C-5003), which is a selective protein arginine methyltransferase 1 (PRMT1) inhibitor, to treat the lung cancer mice model. The in vitro experiment shows that TE-C-5003 has a good anti-tumor effect on lung cancer (IC50 = 0.7022 µM for A549; IC50 = 0.6844 µM for NCL-H1299) and breast cancer (IC50 = 0.4128 µM for MCF-7; IC50 = 0.5965 µM for MDA-MB-231). Anti-tumor experiments in animal models showed that the average growth inhibition rate of xenografted human lung cancer cells by the TE-C-5003-loaded INEI (40% NBCA) was 68.23%, which is far more than TC-E-5003 alone (31.76%). Our study further confirms that INEI is an effective technique to improve the anti-tumor effect. The druggability of small molecule compounds can be improved with the help of the mentioned technology. Also, TC-E-5003 may be developed as a broad spectrum anti-tumor drug.

N-Butyl-2-cyanoacrylate-based injectable and in situ-forming implants for efficient intratumoral chemotherapy.

The local delivery of chemotherapeutic drugs to tumor sites is an effective approach for achieving therapeutic drug concentrations in solid tumors. Injectable implants with the ability to form in situ represent one of the most promising technologies for intratumoral chemotherapy. However, many issues must be resolved before these implants can be applied in clinical practice. Herein, we report a novel injectable in situ-forming implant system composed of n-butyl-2-cyanoacrylate (NBCA) and ethyl oleate, and the sol-gel phase transition is activated by anions in body fluids or blood. This newly developed injectable NBCA ethyl oleate implant (INEI) is biodegradable, biocompatible, and non-toxic. INEI solidifies in several seconds after exposure to body fluids or blood, and the implant's in vivo degradation time can be controlled. In addition, the pore sizes formed by the polymerization of NBCA can be decreased by increasing the NBCA concentration in the implants. Therefore, the drug retention/release time can be adjusted from a few weeks to several months by changing the concentration of NBCA in the implant formulation. Anti-tumor experiments in animal models showed that the average growth inhibition rate of xenografted human breast cancer cells by the paclitaxel-loaded INEI (40% NBCA) was 80%, and they also indicated that tumors in some of the mice were completely eliminated by just a single dosage injection. For the epirubicin-loaded INEI (50% NBCA), the average growth inhibition rate of xenografted human liver cancer cells was 58%. Thus, the chemotherapeutic drug-loaded INEIs exhibited excellent therapeutic efficacy for local chemotherapy.