[Pseudo-targeted metabolomics study of immune stress-mediated idiosyncratic liver injury induced by synergistic effects of bavachin and epimedin B].

Chinese patent medicine preparations containing Epimedii Folium and Psoraleae Fructus have been associated with the occurrence of idiosyncratic drug-induced liver injury(IDILI). However, the specific toxic biomarkers and mechanisms underlying these effects remain unclear. This study aimed to comprehensively assess the impact of bavachin and epimedin B, two principal consti-tuents found in Psoraleae Fructus and Epimedii Folium, on an IDILI model induced by tumor necrosis factor-α(TNF-α) treatment, both in vitro and in vivo. To evaluate the extent of liver injury, various parameters were assessed. Lactate dehydrogenase(LDH) release in the cell culture supernatant, as well as the levels of alanine aminotransferase(ALT) and aspartate transaminase(AST) in mouse plasma were measured. Additionally, histological analysis employing hematoxylin-eosin staining was performed to observe liver tissue changes indicative of the severity of liver injury. Furthermore, a pseudo-targeted metabolomics approach was employed, followed by multivariate analysis, to identify differential metabolites. These identified metabolites were subsequently subjected to Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis. The results showed that at the cellular level, after 2 hours of TNF-α stimulation, bavachin significantly increased the release of LDH in HepG2 cells compared to the normal group and the group treated alone; after the combination of bavachin and epimedin B, the release of LDH further significantly increased on the original basis. Similarly, although the individual or combination treatments of bavachin and epimedin B did not induce liver injury in normal mice, the combination of both drugs induced marked liver injury in TNF-α treated mice, leading to a significant elevation in plasma AST and ALT levels and substantial infiltration of inflammatory immune cells in the liver tissue. Pseudo-targeted metabolomics analysis identified seven common differential metabolites. Among these, D-glucosamine-6-phosphate, N1-methyl-2-pyridone-5-carboxamide, 17beta-nitro-5a-androstane, irisolidone-7-O-glucuronide, and N-(1-deoxy-1-fructosyl) valine emerged as potential biomarkers, with an area under the curve(AUC) exceeding 0.9. Furthermore, our results suggest that the metabolism of nicotinic acid and nicotinamide, as well as the linoleic acid metabolic pathway, may play pivotal roles in bavachin and epimedin B-induced IDILI. In conclusion, within an immune-stressed environment mediated by TNF-α, bavachin and epimedin B appear to induce IDILI through disruptions in metabolic processes.

Exploring the adaptive leisure activities of classified nursing model in elderly colon cancer patients: a perspective on interactive care.

OBJECTIVE: The aims of the study were first to explore the adaptive leisure activities of classified nursing model from the perspective of nurse-patient interactive care, and to explore its impact on the physical and mental health of patients with colon cancer. METHODS: From September 2017 to March 2022 as the observation time node, 82 patients with colon cancer who met the established inclusion and exclusion criteria were regarded as the research objects through the random number table as the grouping tool. The two groups of patients were named as the research group and the control group, with 41 patients in each group. The control group implemented routine nursing measures, and the research group implemented classified nursing mode and adaptive leisure activity mode. The two groups of patients received 4 weeks of nursing intervention. With the help of self-rating anxiety scale, self-rating depression scale, self-care ability evaluation scale and health status survey brief form, the two groups of patients were compared before intervention and at the end of the 4th week after intervention. RESULTS: After the intervention, the anxiety score (t = 6.656, p < 0.001) and depression score (t = 4.851, p < 0.001) of the research group were lower than those of the control group, and the difference was statistically significant. After the intervention, the self-concept (t = 4.845, p < 0.001), self-responsibility (t = 6.071, p < 0.001), self-care skills (t = 3.341, p < 0.001), health knowledge (t = 3.698, p < 0.001) and total score (t = 9.246, p < 0.001) of the research group were higher than those of the control group, and the difference was statistically significant. After the intervention, physical functioning (t = 8.141, p < 0.001), bodily pain (t = 6.083, p < 0.001), general health (t = 9.424, p < 0.001), role-physical (t = 8.057, p < 0.001), role-emotional (t = 13.252, p < 0.001), mental health (t = 12.565, p < 0.001), social functioning (t = 10.813, p < 0.001) and vitality score (t = 12.890, p < 0.001) of the research group were higher than those of the control group, with significant differences. CONCLUSION: Interactive care through adaptive leisure nursing improves mental well-being, self-management, and psychosocial functioning in elderly colon cancer patients, promoting overall health.

Crystal structure of mRNA cap (guanine-N7) methyltransferase E12 subunit from monkeypox virus and discovery of its inhibitors.

In July 2022, the World Health Organization announced monkeypox as a public health emergency of international concern (PHEIC), and over 85,000 global cases have been reported currently. However, preventive and therapeutic treatments for the monkeypox virus (MPXV) remain limited. MPXV mRNA cap N7 methyltransferase (MTase) is composed of two subunits (E1 C-terminal domain (E1CTD) and E12) which are essential for the replication of MPXV. Here, we solved a 2.16 Å crystal structure of E12. We also docked the D1CTD of the vaccinia virus (VACV) corresponding to the E1CTD in MPXV with E12 and found critical residues at their interface. These residues were further used for drug screening. After virtual screening, the top 347 compounds were screened out and a list of top 20 potential MPXV E12 inhibitors were discovered, including Rutin, Quercitrin, Epigallocatechin, Rosuvastatin, 5-hydroxy-L-Tryptophan, and Deferasirox, etc., which were potential E12 inhibitors. Taking the advantage of the previously unrecognized special structure of MPXV MTase composing of E1CTD and E12 heterodimer, we screened for inhibitors targeting MTase for the first time based on the interface between the heterodimer of MPXV MTase. Our study may provide insights into the development of anti-MPXV drugs.

A prospective randomized controlled trial comparing two different treatments of intrauterine adhesions.

RESEARCH QUESTION: Intrauterine adhesions (IUA) are primarily caused by trauma to the endometrium, and hysteroscopy is presently the main treatment for IUA. However, high rates of post-operative adhesion re-formation remain a problem. In this study, the combination of an intrauterine device (IUD) with a Foley catheter and the balloon uterine stent were investigated to evaluate their efficacy in preventing adhesion re-formation and the subsequent reproductive outcomes in patients with moderate to severe adhesions. DESIGN: A prospective randomized controlled study was conducted in a university-affiliated hospital. A total of 171 women with Asherman's syndrome were initially recruited between August 2016 and December 2017 and were randomized to undergo either balloon uterine stent insertion or placement of a contraceptive IUD plus a Foley catheter after hysteroscopic adhesiolysis. Reduction of adhesion scores, incidence of adhesion re-formation, changes in menstrual flow and reproductive outcomes were analysed. RESULTS: A total of 118 participants were eligible for analysis. The American Fertility Society (AFS) scores were not significantly different between groups before hysteroscopic adhesiolysis. At the second-look hysteroscopy, the AFS scores and adhesion recurrence rates were significantly higher in the balloon uterine stent group compared with the combination group (P < 0.01 and P = 0.024, respectively). There were no statistically significant differences in pregnancy and live birth rates between the two groups. CONCLUSIONS: The combination of an IUD and a Foley balloon catheter had better efficacy in preventing adhesion re-formation than the balloon uterine stent alone; however, it did not produce better reproductive outcomes.

Polyethyleneimine-associated polycaprolactone-Superparamagnetic iron oxide nanoparticles as a gene delivery vector.

This study describes the synthesis of novel gene delivery vector with low toxicity and high transfection efficiency for magnetofection. The rational design of magnetofection vector called PPMag (PEI-associated polycaprolactone (PCL)-SPIONs) composed of oleic acid (OA) stabilized superparamagnetic iron oxide nanoparticles (SPPIONs) prepared by thermolysis of iron oleate with a combination of hydrophobic PCL and proton absorbing polymer polyethyleneimine (PEI) (PEI-PCL-SPIONs) is described. Encapsulation of amphiphilic PEI with SPIONs not only improves water dispersity of SPIONs, but also allows nucleic acid (NA) condensation and endosomal/lysosomal escape via proton sponge effect after internalization in cells. MTT cytotoxicity assay showed that cell viability was improved compared to conventional PEI-SPIONs. The luciferase activity of magneto-polyplexes treated cells significantly improved compared to both controls revealed that transfection efficiency of PPMag- pCIKlux polyplexes group was improved compared to naked pCIKlux group. The application underneath of a rare earth magnet significantly improve the transfection efficiency (i.e., the luciferase activity doubles) compared to cells without magnet, indicating that sedimentation induced by magnetic field plays important role in accumulation of magneto-polyplexes on cell surfaces. The results demonstrate that PPMag can be used as a novel gene transfection vector to improve transfection efficiency. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 145-154, 2017.

Receptor-Meditated Endocytosis by Hyaluronic Acid@Superparamagnetic Nanovetor for Targeting of CD44-Overexpressing Tumor Cells.

The present report proposes a more rational hyaluronic acid (HA) conjugation protocol that can be used to modify the surface of the superparamagnetic iron oxide nanoparticles (SPIONs) by covalently binding the targeting molecules (HA) with glutamic acid as a molecular linker on peripheral surface of SPIONs. The synthesis of HA-Glutamic Acid (GA)@SPIONs was included oxidization of nanoparticle's surface with H2O2 followed by activation of hydroxyl group and reacting glutamic acid as an intermediate molecule demonstrating transfection of lung cancer cells. Fourier transform infrared (FTIR) and zeta-potential studies confirmed the chemical bonding between amino acid linker and polysaccharides. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay showed that HA-SPIONs-treated cells remained 82.9% ± 2.7% alive at high particle dosage (200 µg/mL iron concentration), whereas GA-SPIONs and bare SPIONs (B-SPIONs) treated cells had only 59.3% ± 13.4% and 26.5% ± 3.1% survival rate at the same conditions, respectively. Confocal microscopy analysis showed increased cellular internalization of HA-SPIONs compared to non-interacting agarose coated SPIONs (AgA-SPIONs).

Surface activation and targeting strategies of superparamagnetic iron oxide nanoparticles in cancer-oriented diagnosis and therapy.

The advanced fabrication and surface engineering of superparamagnetic iron oxide nanoparticles (SPIONs) could offer excellent physiochemical features for noninvasive tumor imaging and drug delivery. The key issues of realization of maximized selective cancer targeting of SPIONs are minimization of uptake by macrophages, preferential binding to cancerous cells over neighboring normal cells, visualization of tumor cells prior to and after treatment and triggered drug release into target cells in a controlled fashion. In this article, we summarize the current status of fabrication of multifunctional SPION-based nanodevices specially designed for cancer-oriented diagnosis and therapy, with a focus on potential malignancy-targeting ligands' identification and development as nanocarriers. A number of examples of passive and active targeting strategies--lymphoangiogenesis markers, cellular metabolite receptors, extracellular matrix component receptors, neuropeptide receptors and receptor-mediated bypass of the blood-brain barrier--are described in detail.

Development of superparamagnetic iron oxide nanoparticles (SPIONS) for translation to clinical applications.

Superparamagnetic iron oxide nanoparticles (SPIONs) have attract a great deal of interest in biomedical research and clinical applications over the past decades. Taking advantage the fact that SPIONs only exhibit magnetic properties in the presence of an applied magnetic field, they have been used in both in vitro magnetic separation and in vivo applications such as hyperthermia (HT), magnetic drug targeting (MDT), magnetic resonance imaging (MRI), gene delivery (GD) and nanomedicine. Successful applications of SPIONs rely on precise control of the particle's shape, size, and size distribution and several synthetic routes for preparing SPIONs have been explored. Tailored surface properties specifically designed for cell targeting are often required, although the generic strategy involves creating biocompatible polymeric or non-polymeric coating and subsequent conjugation of bioactive molecules. In this review article, synthetic routes, surface modification and functionaliztion of SPIONs, as well as the major biomedical applications are summarized, with emphasis on in vivo applications.