Benzo [a] pyrene-loaded aged polystyrene microplastics promote colonic barrier injury via oxidative stress-mediated notch signalling.

The adsorption of toxic substances on polystyrene microplastics (PSMPs) can modify their biological toxicity and exacerbate the threat to human health. The effects of benzo [a] pyrene (B (a) P)-loaded aged PSMPs on colonic barrier integrity remains unclear. Here, we showed that binding environmentally relevant concentrations of B (a) P alteredl̥ the physicochemical features and markedly enhanced the toxicity of PSMPs. Compared to pristine PSMP, PSMP@B (a) P promoted colonic barrier degradation, body weight loss, colon length shortening, oxidative stress (OS), autophagy, inflammation, and bacterial translocation. Microplastic (MP) exposure induced injury to the colon barrier, including tight junction (TJ) and mucosal barriers, via overactivation of the Notch signalling pathway under increased OS in mice and intestinal organoids. Notably, PSMP@B (a) P exposure exacerbated damage to TJ and the mucosal barrier via the overproduction of reactive oxygen species (ROS), which could be related to the release of B (a) P from PSMP@B (a) P induced by the acidic environment of autophagosomes, which in turn exert synergistic toxic effects with PSMPs. Our study elucidates some of the potential molecular mechanisms by which B (a) P enhances PSMP-related intestinal toxicity, which provides a potential therapeutic approach for diseases caused by PSMP@B (a)P and PSMP pollution.

Melatonin promotes gut anti-oxidative status in perinatal rat by remodeling the gut microbiome.

Gut health is important for nutrition absorption, reproduction, and lactation in perinatal and early weaned mammals. Although melatonin functions in maintaining circadian rhythms and preventing obesity, neurodegenerative diseases, and viral infections, its impact on the gut microbiome and its function in mediating gut health through gut microbiota remain largely unexplored. In the present study, the microbiome of rats was monitoring after fecal microbiota transplantation (FMT) and foster care (FC). The results showed that FMT and FC increased intestinal villus height/crypt depth in perinatal rats. Mechanistically, the melatonin-mediated remodeling of gut microbiota inhibited oxidative stress, which led to attenuation of autophagy and inflammation. In addition, FMT and FC encouraged the growth of more beneficial intestinal bacteria, such as Allobaculum, Bifidobacterium, and Faecalibaculum, which produce more short-chain fatty acids to strengthen intestinal anti-oxidation. These findings suggest that melatonin-treated gut microbiota increase the production of SCFAs, which improve gut health by reducing oxidative stress, autophagy and inflammation. The transfer of melatonin-treated gut microbiota may be a new and effective method by which to ameliorate gut health in perinatal and weaned mammals.

Gut-targeted nanoparticles deliver specifically targeted antimicrobial peptides against Clostridium perfringens infections.

Specifically targeted antimicrobial peptides (STAMPs) are novel alternatives to antibiotics, whereas the development of STAMPs for colonic infections is hindered by limited de novo design efficiency and colonic bioavailability. In this study, we report an efficient de novo STAMP design strategy that combines a traversal design, machine learning model, and phage display technology to identify STAMPs against Clostridium perfringens. STAMPs could physically damage C. perfringens, eliminate biofilms, and self-assemble into nanoparticles to entrap pathogens. Further, a gut-targeted engineering particle vaccine (EPV) was used for STAMPs delivery. In vivo studies showed that both STAMP and EPV@STAMP effectively limited C. perfringens infections and then reduced inflammatory response. Notably, EPV@STAMP exhibited stronger protection against colonic infections than STAMPs alone. Moreover, 16S ribosomal RNA sequencing showed that both STAMPs and EPV@STAMP facilitated the recovery of disturbed gut microflora. Collectively, our work may accelerate the development of the discovery and delivery of precise antimicrobials.

Exposure to BDE-47 causes female infertility risk and induces oxidative stress and lipotoxicity-mediated ovarian hormone secretion disruption in mice.

2,2,4,4-Tetrabromodiphenyl ether (BDE-47) has received considerable attention because of its high level in biological samples and potential developmental toxicity. Whether BDE-47 ingestion affects ovarian hormone secretion and the detailed underlying mechanism have not been clearly elucidated. The present study aimed to evaluate the toxicity of BDE-47 on ovarian hormone secretion and explored the underlying mechanism. The results showed that exposure to BDE-47 caused ovarian lipid deposition and ovarian hormone disruption accompanied by oxidative stress (OS) and downregulation of hormone biosynthesis-related proteins in mice. Mechanistically, using ovarian granulosa cells (GCs) as a cellular model, it was shown that BDE-47 inhibited two ovarian hormone secretion-associated pathways: i) BDE-47 exposure induced OS via the Nrf2/HO-1 signaling pathway and further inhibited the expressions of ovarian hormone biosynthesis-related proteins, such as StAR, 3-ßHSD, CYP11A1, and CYP17A1; ii) BDE-47 induced endoplasmic reticulum (ER) stress, mitochondrial abnormalities, and lipotoxicity, which in turn disrupted the hormone biosynthesis process and inhibited ovarian hormone secretion. Interestingly, autophagy could promote hormone secretion via downregulating the transcription levels of PPARγ and C/EBPα involved in lipid deposition. Moreover, the reactive oxygen species (ROS) scavenger NAC and ER stress inhibitor 4-PBA not only inhibited the decrease in mitochondrial membrane potential but also blocked apoptosis induced by BDE-47, indicating that two individual pathways mediated apoptosis in GCs: the ER stress-mediated signaling pathway and the ROS-mediated mitochondrial signaling pathway. Together, these findings indicate the possible health risks of BDE-47 pollution areas to women, particularly affecting their ovarian hormone secretion.

Effects of kojic acid on boar sperm quality and anti-bacterial activity during liquid preservation at 17 C.

Bacteriospermia is a documented risk to sperm quality when boar semen is stored at 17 °C. The objective of this study was to evaluate the effects of kojic acid (KA) on sperm quality and anti-bacterial effect during liquid storage boar semen at 17 °C, as well as to explore sperm-oocyte binding and embryonic development in vitro. Boar semen was diluted with Beltsville thawing solution (BTS), and it contained KA at different concentrations (0, 0.02, 0.04, 0.06, 0.08, and 0.10 g/L). Bacterial concentrations and sperm quality parameters (motility, mitochondrial membrane potential, acrosome integrity, and plasma membrane integrity) were evaluated on each experimental day. Differences in microbial compositions were compared using 16S rDNA sequencing among the control group, 0.04 g/L KA, and 0.25 g/L gentamycin groups on experimental day 5, and the effects of KA on sperm capacitation, Western blot, total anti-oxidant capacity (T-AOC), reactive oxygen species (ROS) content, malondialdehyde (MDA) content, in vitro fertilization (IVF) parameters, sperm-oocyte binding, cleavage rates, and blastocyst rates were evaluated. The results showed that KA at the optimum concentration of 0.04 g/L significantly improved sperm quality parameters and sperm capacitation, increased T-AOC ability, enhanced IVF parameters and sperm-oocyte binding, increased cleavage and blastocyst rates, inhibited bacterial concentrations, reduced ROS and MDA content, and altered bacterial compositions (P < 0.05). Moreover, KA also increased the expression of anti-oxidant-related proteins, SOD1, SOD2 and CAT, and anti-apoptosis-related protein, Bcl 2, and decreased the expression of apoptosis-related proteins, caspase 3 and Bax in sperm (P < 0.05). These findings demonstrated that supplementation of antibiotic-free extenders for boar semen with 0.04 g/L KA has beneficial effects on liquid boar sperm preservation.

Effects of Isatis root polysaccharide on boar sperm quality during liquid storage and in vitro fertilization.

Liquid preservation of boar semen is a preferred method in pig husbandry, and antioxidants to protect against sperm oxidative stress during periods of storage have become the focus of recent research. Through its antioxidant activity, Isatis root polysaccharide (IRPS), a plant extract, can effectively reduce the cellular lipid peroxidation caused by the accumulation of reactive oxygen species inside mitochondria. In the present study, there was examination of the effects of no supplementation (Control) of a semen extender with or supplementation in different concentrations of IRPS (0.2, 0.4, 0.6, 0.8, and 1.2 mg/mL) on sperm quality variables and antioxidant capacity during liquid storage. The results indicate that after prolonged storage (≥ 3 days), the sperm motility was greater in the group supplemented with 0.6 mg/mL IRPS than in the other groups (P < 0.05). The use of this IRPS concentration also resulted in maintanence of acrosome integrity, plasma membrane integrity, mitochondrial membrane potential, and antioxidant capacity of the sperm (P < 0.05). Furthermore, the results of an in vitro fertilization study indicate IRPS at 0.6 mg/mL markedly increased the sperm fertilization capacity (P < 0.01) and embryonic development to the blastocyst stage (P < 0.05). The addition of 0.6 mg/mL IRPS enhanced the antioxidant capacity of boar sperm, resulting in greater preservation of sperm motility and fertilization capacity during liquid storage. These findings indicate that IRPS has the potential to be used as a component of a semen-preserving diluent to maintain sperm quality during storage.

Evaluation of ε-polylysine as antimicrobial alternative for liquid-stored boar semen.

ε-polylysine (ε-PL) has potent antibacterial effects and is often used in the food industry. However, no studies have clarified the antibacterial effects of ε-PL during storage of boar semen. In this study, boar semen samples were diluted with BTS buffer supplemented with different concentrations (0, 0.04, 0.08, 0.16, 0.32, 0.64, and 1.28 g/L) of ε-PL and different combinations of ε-PL plus gentamicin during liquid storage at 17 °C for 5 days. Bacterial concentrations, bacterial community compositions, sperm quality parameters, and in vitro fertilization (IVF) were evaluated in order to analyze the antibacterial effects of these parameters during boar semen preservation. The results indicated that the optimum concentration of ε-PL was 0.16 g/L, which significantly improved sperm quality parameters, including sperm motility, plasma membrane integrity, mitochondrial membrane potential, and acrosome integrity, and changed bacterial proliferation and composition (P < 0.05). Moreover, compared with the control group, IVF parameters in the treatment groups also significantly improved (P < 0.05), although there were no significant differences among treatment groups. Interestingly, the antibacterial effect of 0.16 g/L ε-PL in combination with 0.125 g/L gentamycin was similar to that of 0.25 g/L gentamicin alone. In conclusion, our results showed that 0.16 g/L ε-PL is promising for the replacement of gentamicin to improve sperm quality parameters, sperm capacitation, and IVF by reducing bacterial concentrations and disrupting bacterial community composition.

Effects of oligomeric proanthocyanidins on quality of boar semen during liquid preservation at 17 °C.

The use of antioxidants is an important aspect in the preservation of boar semen. Oligomeric proanthocyanidins (OPC) are an effective natural antioxidants that scavenges free radicals and reactive oxygen species (ROS). This study was designed to investigate the antioxidative effect of OPC on boar semen quality during liquid preservation at 17 °C. The effects of different concentrations of OPC on sperm quality variables, antioxidant effects and fertility were analyzed in this experiment. Semen collected from six Guanzhong-Black boars and was diluted with Beltsville thawing solution (BTS). During the process of liquid preservation at 17 °C, the variables assessed were measured and analyzed every 24 h. The addition of OPC improved boar sperm motility, acrosome integrity, membrane integrity, and mitochondrial membrane potential as compared with that of the control group (P < 0.05). Meanwhile, malondialdehyde content (MDA) and ROS content was less after adding OPC, thereby improving the total antioxidant capacity (T-AOC) (P < 0.05). Different concentrations of OPC have different degrees of protective effects on boar semen quality. The results indicate that 50 µg/mL of OPC was the optimum concentration, and that the conception rate, litter size, and survival rate increased at this concentration as compared with that of the control group (P < 0.05). In summary, the addition of OPC to BTS diluents can improve the quality of boar semen at 17 °C during liquid preservation. Further research is needed to understand the mechanism by which OPC provides protection to boar semen during preservation in vitro.