JUN mediates the senescence associated secretory phenotype and immune cell recruitment to prevent prostate cancer progression.

BACKGROUND: Prostate cancer develops through malignant transformation of the prostate epithelium in a stepwise, mutation-driven process. Although activator protein-1 transcription factors such as JUN have been implicated as potential oncogenic drivers, the molecular programs contributing to prostate cancer progression are not fully understood. METHODS: We analyzed JUN expression in clinical prostate cancer samples across different stages and investigated its functional role in a Pten-deficient mouse model. We performed histopathological examinations, transcriptomic analyses and explored the senescence-associated secretory phenotype in the tumor microenvironment. RESULTS: Elevated JUN levels characterized early-stage prostate cancer and predicted improved survival in human and murine samples. Immune-phenotyping of Pten-deficient prostates revealed high accumulation of tumor-infiltrating leukocytes, particularly innate immune cells, neutrophils and macrophages as well as high levels of STAT3 activation and IL-1ß production. Jun depletion in a Pten-deficient background prevented immune cell attraction which was accompanied by significant reduction of active STAT3 and IL-1ß and accelerated prostate tumor growth. Comparative transcriptome profiling of prostate epithelial cells revealed a senescence-associated gene signature, upregulation of pro-inflammatory processes involved in immune cell attraction and of chemokines such as IL-1ß, TNF-α, CCL3 and CCL8 in Pten-deficient prostates. Strikingly, JUN depletion reversed both the senescence-associated secretory phenotype and senescence-associated immune cell infiltration but had no impact on cell cycle arrest. As a result, JUN depletion in Pten-deficient prostates interfered with the senescence-associated immune clearance and accelerated tumor growth. CONCLUSIONS: Our results suggest that JUN acts as tumor-suppressor and decelerates the progression of prostate cancer by transcriptional regulation of senescence- and inflammation-associated genes. This study opens avenues for novel treatment strategies that could impede disease progression and improve patient outcomes.

[Nail and fingertip injuries: a practical guide for general practitioners]. / Traumatismes de l'ongle et de l'extrémité digitale : guide pratique pour le médecin de premier recours.

Nail and fingertip injuries account for approximately 15 to 24% of hand injuries and are particularly frequent among young and active patients. Despite their prevalence they are often overlooked and considered as cosmetology. However, the nail unit involves complex anatomical structures that help to improve the sensitivity and fine motor skills of the fingers and protect the distal phalanx. If not treated correctly, these injuries can generate significant functional impairments. This article aims to present the most frequently encountered traumas, their anatomical and physiological involvement, and their management in the standard practice of the general practitioner.

Les traumatismes unguéaux et de l'extrémité des doigts représentent 15 à 24 % des lésions de la main et sont particulièrement fréquents chez les jeunes patients actifs. Malgré leur prévalence, ils sont souvent négligés et considérés comme de la cosmétologie. Or l'ongle et la partie distale du doigt comportent des structures anatomiques complexes qui participent à améliorer la sensibilité, la motricité fine et à protéger les phalanges distales. Les traumatismes de ces structures, s'ils ne sont pas pris en charge correctement, peuvent engendrer des séquelles fonctionnelles importantes. Cet article a pour but de présenter les traumatismes les plus fréquemment rencontrés, leur implication anatomique et physiologique ainsi que leur prise en charge dans la pratique courante de médecine de premier recours.

Olive Oil as a Transport Medium for Bioactive Molecules of Plants?-An In Situ Study.

(1) Caries and erosions still remain a challenge for preventive dentistry. Certain plant extracts have shown beneficial effects in preventive dentistry. The aim of this study was to evaluate the antibacterial, anti-adherent and erosion-protective properties of ellagic acid (EA) as a polyphenolic agent. The combination with olive oil was investigated additionally to verify a possible improved bioactive effect of EA. (2) An in situ study was carried out with six subjects. Individual splints were prepared with bovine enamel specimens. The splints were worn for 1 min (pellicle formation time). Thereafter, 10 min rinses were performed with EA in water/in oil. Bacterial adherence was evaluated by fluorescence microscopy (DAPI, ConA, BacLight) after an 8 h oral exposition time. Additionally, the splints were worn for 30 min to quantify demineralization processes. The ultrastructure of the pellicle was investigated after an oral exposure time of 2 h under a transmission electron microscope. Statistical analysis was performed by Kruskal-Wallis tests, Mann-Whitney U tests and Bonferroni-Holm correction. (3) Rinsing with EA led to a significant reduction of adherent vital and dead bacteria. The combination with olive oil did not improve these outcomes. The assessment of glucan structures after rinsing with EA in water showed significant effects. Significant differences were observed for both rinses in calcium release at pH 3.0. After rinsing with EA in oil, significantly less calcium was released compared to rinsing with EA in water (pH = 3.0). (4) Olive oil is not suitable as a transport medium for lipophilic polyphenols. EA has anti-adherent and antibacterial properties in situ. EA also shows erosion-protective effects, which can be enhanced in combination with olive oil depending on the pH value. Ellagic acid has a neutral pH and could be an opportunity in the treatment of specific patient groups (xerostomia or mucositis).

Prevention of Dental Biofilm Formation with Polyphenols: A Systematic Review.

Polyphenols are plant secondary products with health-promoting properties against various degenerative or infectious diseases, and thus may help in the prevention of oral diseases. The aim of the present systematic review was to investigate polyphenols as a possible adjuvant in inhibiting dental biofilm formation, which is an important precondition for the most prevalent oral disease - caries and periodontitis. A literature search was conducted using the databases PubMed, CENTRAL and Scopus. Only studies with oral healthy participants and plaque level as outcome were included. Data search and extraction was conducted by two authors independently. Of the 211 initially identified studies, only six met all inclusion criteria. Meta-analysis was performed with five studies using the random effect model. Treatment with polyphenols reduced the plaque level in comparison to a negative control, but not significantly. Strong evidence of heterogeneity was observed. The diversity and complexity of polyphenols and their preparation need to be considered. There is no clear evidence that clinical use of polyphenols can prevent dental biofilm formation. Additional research with more and larger randomized controlled trials are required.

[Anemia: new developments and diagnostic and management strategies]. / Anémie: nouveautés et stratégies diagnostiques et de prise en charge.

Anemia is a major public health problem that affects approximately 25% of the world's population. Its prevalence is increased in certain populations: it affects 40% of pregnant women, 42% of children under 5 years old and it increases with age from 50 years old. Anemia can be an emergency in case of hemorrhage or acute hemolysis, but it is most often chronic. Anemia can be constitutional or acquired. In the second case, iron or vitamin deficiencies are the most frequent causes. Anemia can also be a diagnostic pointing to hypothyroidism, inflammatory disease, or cancer. In this article, we provide an update on diagnostic and management strategies for anemia and discuss new scientific developments.

Véritable problème de santé publique, l'anémie touche environ 25% de la population mondiale. Sa prévalence est accrue dans certains groupes: elle concerne 40% des femmes enceintes, 42% des enfants de moins de 5 ans et augmente avec l'âge dès 50 ans. L'anémie peut être une urgence en cas d'hémorragie ou d'hémolyse aiguë mais elle est le plus souvent chronique. Les anémies peuvent être constitutionnelles ou acquises. Dans le 2e cas, les carences martiales ou vitaminiques sont les causes les plus fréquentes. L'anémie peut aussi être un diagnostic orientant vers une hypothyroïdie, une maladie inflammatoire ou un cancer. Dans cet article, nous abordons les nouveautés scientifiques relatives à l'anémie et faisons le point sur les stratégies pour la diagnostiquer et la prendre en charge.

Preventive Applications of Polyphenols in Dentistry-A Review.

Polyphenols are natural substances that have been shown to provide various health benefits. Antioxidant, anti-inflammatory, and anti-carcinogenic effects have been described. At the same time, they inhibit the actions of bacteria, viruses, and fungi. Thus, studies have also examined their effects within the oral cavity. This review provides an overview on the different polyphenols, and their structure and interactions with the tooth surface and the pellicle. In particular, the effects of various tea polyphenols on bioadhesion and erosion have been reviewed. The current research confirms that polyphenols can reduce the growth of cariogenic bacteria. Furthermore, they can decrease the adherence of bacteria to the tooth surface and improve the erosion-protective properties of the acquired enamel pellicle. Tea polyphenols, especially, have the potential to contribute to an oral health-related diet. However, in vitro studies have mainly been conducted. In situ studies and clinical studies need to be extended and supplemented in order to significantly contribute to additive prevention measures in caries prophylaxis.