Remodeling of tumor microenvironment by extracellular matrix protein 1a differentially regulates ovarian cancer metastasis.

We previously reported that extracellular matrix protein 1 isoform a (ECM1a) promotes epithelial ovarian cancer (EOC) through autocrine signaling by binding to cell surface receptors αXß2. However, the role of ECM1a as a secretory molecule in the tumor microenvironment is rarely reported. In this study, we constructed murine Ecm1-knockout mice and human ECM1a-knockin mice and further generated orthotopic or peritoneal xenograft tumor models to mimic the different metastatic stages of EOC. We show that ECM1a induces oncogenic metastasis of orthotopic xenograft tumors, but inhibits early-metastasis of peritoneal xenograft tumors. ECM1a remodels extracellular matrices (ECM) and promotes remote metastases by recruiting and transforming bone marrow mesenchymal stem cells (BMSCs) into platelet-derived growth factor receptor beta (PDGFRß+) cancer-associated fibroblasts (CAFs) and facilitating the secretion of angiopoietin-like protein 2 (ANGPTL2). Competing with ECM1a, ANGPTL2 also binds to integrin αX through the P1/P2 peptides, resulting in negative effects on BMSC differentiation. Collectively, this study reveals the dual functions of ECM1a in remodeling of TME during tumor progression, emphasizing the complexity of EOC phenotypic heterogeneity and metastasis.

Long-term sorbitol consumption affects the hippocampus and alters cognitive function in aged mice.

The systemic effects of the artificial sweetener sorbitol on older adult individuals have not been elucidated. We assessed the effects of sorbitol consumption on cognitive and gingival health in a mouse model. Aged mice were fed 5% sorbitol for 3 months before their behavior was assessed, and brain and gingival tissues were collected. Long-term sorbitol consumption inhibited gingival tissue aging in aged mice. However, it caused cognitive decline and decreased brain-derived neurotrophic factor (BDNF) in the hippocampus. Sorbitol consumption did not affect homeostatic function; however, it may exert effects within the brain, particularly in the hippocampus.

Effects of tooth loss on behavioral and psychological symptoms of dementia in app knock-in mice.

OBJECTIVES: Many patients with Alzheimer's disease (AD) experience behavioral and psychological symptoms of dementia (BPSD), which significantly affect their quality of life. It is known that 5-Hydroxytryptamine (5-HT) plays a crucial role in the development of BPSD. While the relationship between tooth loss and AD symptoms has been acknowledged, the aspect of aggression has not been focused on until now. Despite the established importance of 5-HT in BPSD, how tooth loss is related to the exacerbation of AD symptoms, especially in terms of aggression, remains largely unexplored. Although nutritional status is known to influence the progression of dementia, the specific effect of tooth loss on peripheral symptoms, notably aggression, is not well understood. METHODS: In our study, we conducted maxillary molar extractions in aged C57BL/6J and AppNL-G-F mice and observed their condition over a 3-month period. During this time, we documented significant behavioral and genetic differences between mice in the control groups and mice that underwent tooth extraction. Notably, mice that underwent tooth extraction exhibited a considerable decline in cognitive function and increased in aggression 3 months after tooth extraction compared with the control groups (C57BL/6J and AppNL-G-Fmice). RESULTS: Our findings suggest that molar loss may lead to reduced 5-HT levels in the hippocampus, possibly mediated by the trigeminal nerve, contributing to the development of aggression and BPSD in AD. CONCLUSION: This study sheds light on the intricate relationships between oral health, 5-HT, and AD symptoms, offering valuable insights into potential therapeutic avenues for managing BPSD in patients with dementia.

Correction: Furukawa et al. Long-Term Soft-Food Rearing in Young Mice Alters Brain Function and Mood-Related Behavior. Nutrients 2023, 15, 2397.

In the original publication [...].

Integrating cfDNA liquid biopsy and organoid-based drug screening reveals PI3K signaling as a promising therapeutic target in colorectal cancer.

BACKGROUND: The current precision medicine relies on biomarkers, which are mainly obtained through next-generation sequencing (NGS). However, this model failed to find effective drugs for most cancer patients. This study tried to combine liquid biopsy with functional drug tests using organoid models to find potential drugs for cancer patients. METHODS: Colorectal cancer (CRC) patients were prospectively enrolled and blood samples were collected from patients before the start of treatment. Targeted deep sequencing of cfDNA samples was performed using a 14-gene panel. Gastrointestinal (GI) cancer organoids were established and PI3K and mTOR inhibitors were evaluated on organoid models. RESULTS: A total of 195 mutations were detected across 58 cfDNA samples. The most frequently mutated genes were KRAS, TP53, PIK3CA, and BRAF, all of which exhibited higher mutation rates than tissue biopsy. Although 81% of variants had an allele frequency of less than 1%, certain mutations in KRAS, TP53, and SMAD4 had high allele frequencies exceeding 10%. Notably, among the seven patients with high allele frequency mutations, six had metastatic tumors, indicating that a high allele frequency of ctDNA could potentially serve as a biomarker of later-stage cancer. A high rate of PIK3CA mutation (31 out of 67, or 46.3%) was discovered in CRC patients, suggesting possible tumor progression mechanisms and targeted therapy opportunities. To evaluate the value of anti PI3K strategy in GI cancer, different lines of GI cancer organoids were established. The organoids recapitulated the morphologies of the original tumors. Organoids were generally insensitive to PI3K inhibitors. However, CRC-3 and GC-4 showed response to mTOR inhibitor Everolimus, and GC-3 was sensitive to PI3Kδ inhibitor Idelalisib. The CRC organoid with a PIK3CA mutation showed greater sensitivity to the PI3K inhibitor Alpelisib than wildtype organoids, suggesting potential treatment options for the corresponding patients. CONCLUSION: Liquid biopsy holds significant promise for improving precision treatment and tumor prognosis in colorectal cancer patients. The combination of biomarker-based drug prediction with organoid-based functional drug sensitivity assay may lead to more effective cancer treatment.

Premature gray hair development in the interbrow region owing to the loss of maxillary first molars in young mice.

The exact sites of premature hair graying and whether tooth loss causes this condition remain unknown. In this study, we aimed to explore the effect of reduced mastication on premature hair graying. Maxillary first molars were extracted from young mice, and the mice were observed for 3 months, along with non-extraction control group mice. After 3 months, gray hair emerged in the interbrow region of mice in the tooth extraction group but not in the control group. The expression of tyrosinase-related protein-2 (TRP-2) mRNA was lower in the interbrow tissues of young mice without maxillary molars than in those with maxillary molars. Tooth loss leads to interbrow gray hair growth, possibly because of weakened trigeminal nerve input, suggesting that reduced mastication causes premature graying. Thus, prompt prosthetic treatment after molar loss is highly recommended.

Genome-wide identification, phylogeny and expressional profile of the Dmrt gene family in Chinese sturgeon (Acipenser sinensis).

Chinese sturgeon Dmrt gene family was identified and characterized for the first time. A total of 5 putative Dmrt genes were identified. The gene structure, conserved protein domain and the phylogenetic relationship of Dmrt gene family were systematically analyzed. The expressed profile of Chinese sturgeon Dmrt genes in gonad, pituitary and hypothalamus in the male and female were investigated. The results indicated that the accumulation of Dmrt genes was involved in different tissues, and the expression profile also differed among each Dmrt genes. ASDmrt1A, ASDmrt2, ASDmrt3, and ASDmrtA1 were highly expressed in the testis in comparison with other tissue. This result showed that ASDmrt1A, ASDmrt2, ASDmrt3, and ASDmrtA1 played an important role in the development of testicle, and may be useful tool in distinguishing between male and female of Chinese sturgeon. Our study will provide a basis for additional analyses of Chinese sturgeon Dmrt genes. This systematic analysis provided a foundation for further functional characterization of Dmrt genes with an aim of study of Chinese sturgeon Dmrt gene family.

Analysis of the Value of Physical Activity to Children's Mental Health Education in the Epidemic Era / Análisis del valor de la actividad física para la educación sobre salud mental de los niños en la era epidémica

This research aims to examine the contribution of physical activity to children's mental health education during the epidemic era. In this study, 50 5- to 6-year-old children from a city were recruited as research subjects using interviews, literature review, and experimental statistics and then randomly divided into two groups: the experimental group and the control group. The psychological index data before and after the happy exercise were measured using a questionnaire survey. The psychological index data before and after 12 weeks of experimental practice were evaluated using data statistics. Six mental health indices demonstrated a significant difference between the experimental group and the control group, with the improvement value of the experimental group's movement score being 3.68 and the improvement value of the control group's movement score being 0.15. Social score improvement in the experimental group was 1.76, whereas, in the control group, it was 0.12. The value of language score improvement was 1.16, while the language score improvement in the control group was 0.14. The gymnastics sports curriculum is favorable to the mental health development of 56-year-old children and has significantly enhanced children's mental health.(AU)