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Objective To analyze the modeling elements and subjects of the animal model of skin photoaging, and to provide a reference for the preparation and improvement of the model and a basis for the scientific evaluation of the subject. Methods By searching and collecting relevant literature on the preparation of animal models of skin photoaging from 2010 to 2022 in the China National Knowledge Infrastructure, Wanfang Database, and PubMed database, the model animal species, gender, modeling method, modeling cycle, radiation source and its distance from the modeling site, cumulative radiation volume, detection indicators, and subjects (drugs or treatments) recorded in the literature were collated and summarized, and a database was established for statistical analysis. Results 257 articles that met the inclusion criteria were selected. Among them, the most common animal model was SKH-1 hairless mice, followed by SD rats and KM mice; the gender of animals was mainly female, medium-wave ultraviolet B (UVB) was often used as the radiation source, the distance between the radiation source and the modelling site was mostly 30 cm, and the modelling period was usually 40-60 days. The cumulative dose of long-wave ultraviolet A (UVA) was between 100-150 J/cm2, and the cumulative dose of UVB was between 5-10 J/cm2. The tests used after model establishment were skin histopathological examination, skin tissue homogenization, fibre staining, immunoblotting, etc. Subjects included Chinese herbal medicines, Chinese herbal extracts, Chinese patent medicines, Chinese herbal compound medicines, chemical drugs, biological agents and other treatments, while the animal model of skin photoaging was also used for clinical efficacy studies of external Chinese medicine, physiotherapy and positive control drugs. Conclusion In skin photoaging animal experiments, female SKH-1 hairless mice are often used, and UVB is used as the radiation source. The modeling period is usually 40-60 days, and the minimum erythema dose (MED) is incremented week by week. The cumulative UVB irradiation dose ranges from 0 to 10 J/cm2, which has the advantages of high success rate, good reproducibility and high similarity with clinical disease.

Background In the last decade, veterinary antimicrobial usage (AMU) and antimicrobial resistance (AMR) among indicator bacteria in livestock have decreased substantially in the Netherlands. The extent to which this decrease has affected AMR levels among human infections remains unclear. Objectives To assess the association between AMU in livestock and AMR in Escherichia coli isolates from human urinary tract infections (UTIs). Methods Data on AMR and AMU between 2009 and 2020 from Dutch national surveillance programmes for humans and livestock were used. Associations between AMU in four major livestock sectors and AMR in humans were assessed for 10 antimicrobial classes and the ESBL resistance profile, using logistic regression analysis. Associations between AMU and AMR in livestock, between AMR in livestock and in humans, and between AMU and AMR in humans were also assessed. Results Statistical significance was reached for 16/31 of the tested associations between AMU in livestock and AMR in human E. coli UTIs. Of the significant associations, 11 were positive (OR 1.01–1.24), whereas 5 were negative (OR 0.96–0.99). All associations between human AMU and AMR in E. coli isolates from UTIs were positive and statistically significant. Weak but significant positive correlations were also observed between livestock AMR and human AMR. Conclusions Although several significant associations between AMU in livestock and AMR in human UTIs caused by E. coli were observed, the associations between AMU and AMR were generally stronger within the human and animal populations. This indicates that potential zoonotic spread of AMR in E. coli causing human UTIs from livestock sources is limited. [ABSTRACT FROM AUTHOR]

Background: Targeted therapy for triple‐negative breast cancer (TNBC) remains a challenge. N6‐methyladenosine (m6A) is the most abundant internal mRNA modification in eukaryotes, and it regulates the homeostasis and function of modified RNA transcripts in cancer. However, the role of leucine‐rich pentatricopeptide repeat containing protein (LRPPRC) as an m6A reader in TNBC remains poorly understood. Methods: Western blotting, reverse transcription‐polymerase chain reaction (RT‐qPCR) and immunohistochemistry were used to investigate LRPPRC expression levels. Dot blotting and colorimetric enzyme linked immunosorbent assay (ELISA) were employed to detect m6A levels. In vitro functional assays and in vivo xenograft mouse model were utilised to examine the role of LRPPRC in TNBC progression. Liquid chromatography–mass spectrometry/mass spectrometry and Seahorse assays were conducted to verify the effect of LRPPRC on glycolysis. MeRIP‐sequencing, RNA‐sequencing, MeRIP assays, RNA immunoprecipitation assays, RNA pull‐down assays and RNA stability assays were used to identify the target genes of LRPPRC. Patient‐derived xenografts and organoids were employed to substantiate the synthetic lethality induced by LRPPRC knockdown plus glutaminase inhibition. Results: The expressions of LRPPRC and m6A RNA were elevated in TNBC, and the m6A modification site could be recognised by LRPPRC. LRPPRC promoted the proliferation, metastasis and glycolysis of TNBC cells both in vivo and in vitro. We identified lactate dehydrogenase A (LDHA) as a novel direct target of LRPPRC, which recognised the m6A site of LDHA mRNA and enhanced the stability of LDHA mRNA to promote glycolysis. Furthermore, while LRPPRC knockdown reduced glycolysis, glutaminolysis was enhanced. Moreover, the effect of LRPPRC on WD40 repeat domain‐containing protein 76 (WDR76) mRNA stability was impaired in an m6A‐dependent manner. Then, LRPPRC knockdown plus a glutaminase inhibition led to synthetic lethality. Conclusions: Our study demonstrated that LRPPRC promoted TNBC progression by regulating metabolic reprogramming via m6A modification. These characteristics shed light on the novel combination targeted therapy strategies to combat TNBC. [ABSTRACT FROM AUTHOR]

Celastrol, an active triterpenoid extracted from one of the most famous traditional Chinese medicines (TCMs), Tripterygium wilfordii Hook.f., is a novel anti-cancer drug with significant anti-angiogenesis activity. However, the exact molecular mechanisms underlying its anti-tumor angiogenesis effect remain unclear. The process of angiogenesis needs lots of energy supply, which mostly derives from mitochondria, the "energy factory" in our body. This study shows that celastrol exerts visible suppression on tumor growth and angiogenesis in a cell-derived xenograft (CDX). Likewise, it reduced the tube formation and migration of human umbilical vein endothelial cells (HUVECs), suppressed the energy metabolism of mitochondria in the Seahorse XF Mito Stress Test, and triggered mitochondrial fragmentation and NF-κB activation. Mechanically, celastrol downregulated the expression of mitochondrial-sharping protein optic atrophy protein 1 (OPA1), which was further estimated by the OPA1 knockdown model of HUVECs. Specifically, celastrol directly suppressed OPA1 at the mRNA level by inhibiting the phosphorylation of STAT3, and stattic (STAT3 inhibitor) showed the same effects on OPA1 suppression and anti-angiogenesis activity. Overall, this study indicates that celastrol inhibits tumor angiogenesis by suppressing mitochondrial function and morphology via the STAT3/OPA1/P65 pathway and provides new insight for mitochondrion-targeted cancer therapy. [ABSTRACT FROM AUTHOR]