Enhanced Therapeutic Potential of Hybrid Exosomes Loaded with Paclitaxel for Cancer Therapy.

The advancement of exosome studies has positioned engineered exosomes as crucial biomaterials for the development of advanced drug delivery systems. This study focuses on developing a hybrid exosome system by fusing mesenchymal stem cells (MSCs) exosomes with folate-targeted liposomes. The aim was to improve the drug loading capacity and target modification of exosome nanocarriers for delivering the first-line chemotherapy drug paclitaxel (PTX) and its effectiveness was assessed through cellular uptake studies to evaluate its ability to deliver drugs to tumor cells in vitro. Additionally, in vivo experiments were conducted using a CT26 tumor-bearing mouse model to assess the therapeutic efficacy of hybrid exosomes loaded with PTX (ELP). Cellular uptake studies demonstrated that ELP exhibited superior drug delivery capabilities to tumor cells in vitro. Moreover, in vivo experiments revealed that ELP significantly suppressed tumor growth in the CT26 tumor-bearing mouse model. Notably, for the first time, we examined the tumor microenvironment following intratumoral administration of ELP. We observed that ELP treatment activated CD4+ and CD8+ T cells, reduced the expression of M2 type tumor-associated macrophages (TAMs), polarized TAMs towards the M1 type, and decreased regulatory T cells (Tregs). Our research highlights the considerable therapeutic efficacy of ELP and its promising potential for future application in cancer therapy. The development of hybrid exosomes presents an innovative approach to enhance drug delivery and modulate the tumor microenvironment, offering exciting prospects for effective cancer treatment strategies.

Effects of pork sausage on intestinal microecology and metabolism in mice.

BACKGROUND: Processed meat, as an important part of the human diet, has been recognized as a carcinogen by the International Agency for Research on Cancer (IARC). Although numerous epidemiological reports supported the IARC's view, the relevant evidence of a direct association between processed meat and carcinogenicity has been insufficient and the mechanism has been unclear. This study aims to investigate the effects of pork sausage (as a representative example of processed meat) intake on gut microbial communities and metabolites of mice. Microbial communities and metabolites from all groups were analyzed using 16S rRNA gene sequencing and Ultra performance liquid chromatography-quadrupole-time of flight-mass spectrometer (UPLC-Q-TOF/MS), respectively. RESULTS: The levels of Bacteroidetes, Bacteroides, Alloprevotella, Lactobacillus, Prevotella_9, Lachnospiraceae_NK4A136_group, Alistipes, Blautia, Proteobacteria, Firmicutes, Allobaculum, Helicobacter, Desulfovibrio, Clostridium_sensu_stricto_1, Ruminococcaceae_UCG-014, Lachnospiraceae_UCG-006 and Streptococcus (P < 0.05) were obviously altered in the mice fed a pork sausage diet. Twenty-seven metabolites from intestinal content samples and fourteen matabolites from whole blood samples were identified as potential biomarkers from multivariate analysis, including Phosphatidic acid (PA), Sphingomyelin (SM), Lysophosphatidylcholine (LysoPC), Diglyceride (DG), D-maltose, N-acylamides and so forth. The significant changes in these biomarkers demonstrate metabonomic variations in pork sausage treated rats, especially carbohydrate metabolism, lipid metabolism, and amino acid metabolism. CONCLUSION: The present study provided evidence that a processed meat diet can increase the risk of colorectal cancer and other diseases significantly by altering the microbial community structure and disrupting the body's metabolic pathways. © 2023 Society of Chemical Industry.

Reduction of Ultrafiltration Membrane Fouling by the Pretreatment Removal of Emerging Pollutants: A Review.

Ultrafiltration (UF) processes exhibit high removal efficiencies for suspended solids and organic macromolecules, while UF membrane fouling is the biggest obstacle affecting the wide application of UF technology. To solve this problem, various pretreatment measures, including coagulation, adsorption, and advanced oxidation, for application prior to UF processes have been proposed and applied in actual water treatment processes. Previously, researchers mainly focused on the contribution of natural macromolecular pollutants to UF membrane fouling, while the mechanisms of the influence of emerging pollutants (EPs) in UF processes (such as antibiotics, microplastics, antibiotic resistance genes, etc.) on membrane fouling still need to be determined. This review introduces the removal efficiency and separation mechanism for EPs for pretreatments combined with UF membrane separation technology and evaluates the degree of membrane fouling based on the UF membrane's materials/pores and the structural characteristics of the cake layer. This paper shows that the current membrane separation process should be actively developed with the aim of overcoming specific problems in order to meet the technical requirements for the efficient separation of EPs.

Simultaneous separation of glycyrrhizic acid, baicalein and wogonin from Radix Glycyrrhizae and Radix Scutellariae using foam fractionation and in vitro activity evaluation.

BACKGROUND: In this study, the optimal conditions for the extraction and purification of glycyrrhizic acid from Radix Glycyrrhizae (RG) and baicalein and wogonin from Radix Scutellariae (RS) by foam fractionation were studied on the basis of central composite design (CCD) and response surface methodology. RESULTS: The results showed that herbal proportion (RG:RS), gas flow and ethanol concentration were the main factors guiding the foam fractionation of RG and RS. The optimum technological parameters were obtained as follows: herbal proportion (RG:RS), 1.86:1.14; gas flow, 109 mL min-1 ; and ethanol concentration, 53%. Under the optimal operating conditions, the maximal extraction yields of baicalein, glycyrrhizic acid and wogonin were 56.67, 13.25 and 9.51 mg g-1 , respectively, which were 2.32-, 1.22- and 1.84-fold higher than those of ultrasonic extraction and 17.28-, 1.15- and 9.91-fold higher than those of ultrasonic extraction without hydrolysis, respectively. Investigations on the antioxidant activity showed that the foam-fractionated extract exhibited better free radical scavenging activity (IC50 13.80 µg mL-1 ) than that of the ultrasonic extract (IC50 223.00 µg mL-1 ). Antibacterial activity showed that the minimum inhibitory concentrations of the foam fractionated extract against Staphylococcus aureus, Candida albicans, Group A Streptococcus and Pseudomonas aeruginosa were 1.38, 1.38, 0.69 and 5.50 mg mL-1 , respectively. CONCLUSION: The results indicate that the foam fractionated extract exhibited better extraction yields and free radical scavenging activity than did the ultrasonic extract. Therefore, this fast and eco-friendly method was established and could be a basis for the extraction and separation of other active constituents from herbal medicines. © 2022 Society of Chemical Industry.

Mg/Al-LDH as a nano-adjuvant for pertussis vaccine: a evaluation compared with aluminum hydroxide adjuvant.

Background. Layered double hydroxide (LDH) has been demonstrated as a highly efficient antigen platform to induce effective and durable immune response. However, whether LDH nanoparticles could act as an adjuvant for pertussis vaccines is still unknown. Here we evaluated the potential of Mg/Al-LDH as a nano-adjuvant to improve immune response against pertussis and compared it with commercial aluminum hydroxide (AH) adjuvant.Method. The Mg/Al-LDH nanoparticles were synthesized by a hydrothermal reaction. The morphology, structure and size of Mg/Al-LDH were characterized by transmission electron microscope, x-ray diffraction and MALVERN particle analysis. The ovalbumin and Pertussis toxin (PTd) was adsorbed to Mg/Al-LDH. The immune response of antigen-LDH complex was evaluated in mice, compared with commercial adjuvant alum. Hematoxylin-eosin staining was used to evaluate the inflammatory response at injection site.Results. The synthetic Mg/Al-LDH nanoparticles showed a typical hexagonal lamellar structure. The average size of synthetic nanoparticles was 102.9 nm with PDI of 0.13 and zeta potential was 44.4 mV. Mg/Al-LDH nanoparticles effectively adsorbed protein antigen and mediated antigen uptake by DC cells. Animal experiments showed that Mg/Al-LDH gave enhancement in anti-pertussis toxin (PTd) humoral immune response, which was considerable to commercial AH adjuvant. Finally, Mg/Al-LDH produced a slighter inflammatory response than AH at injection site and this injury was quickly recovered.Conclusion. Our study demonstrated the potential of Mg/Al-LDH as an effective adjuvant for pertussis vaccine, which induced comparable antibody response and had a better safety compared with commercial AH adjuvant.

Alteration in concentration-response curves of four N-alkylpyridinium chloride by exposure concentration, time and in their mixtures by uniform design.

The concentration-response curves (CRCs) of chemicals are important in extrapolating their effects from laboratory studies to their risk assessment in the field. Yet, the CRCs can be altered by exposure concentration and mixture conditions, and also by exposure time in recent reports. Presently, ionic liquids (N-alkylpyridinium chloride, [apyr]Cl) were used for CRC-alteration studies. In individual effects on Vibrio qinghaiensis sp. Q67 (Q67) from 0.25 to 24 h, the CRCs of [epyr]Cl and [bpyr]Cl changed from S- to J-shaped with decreases in inhibition and increases in stimulation, while the CRCs of [hpyr]Cl changed from S- to flat-shape with decreases in inhibition but without stimulation. In mixture effects on Q67, the CRCs all changed from S- to J-shaped from 0.25 to 24 h. By means of the variable selection and modeling method based on the prediction (VSMP), the CRC-alterations of mixtures were positively contributed by [epyr]Cl but negatively contributed by [bpyr]Cl. Furthermore, a parameter was developed by the area of a triangular that combined acute inhibition (EC50,0.25h) and chronic stimulation (Zero-effect Point, i.e., ZEP24h and the minimum inhibition effect, i.e., Emin,24h). This parameter successfully evaluated the CRC-alterations in both individual and mixture effects over time, and indicated potential interactions in CRC-alteration in mixtures.