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.

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.

Erythritol Can Inhibit the Expression of Senescence Molecules in Mouse Gingival Tissues and Human Gingival Fibroblasts.

Oral aging causes conditions including periodontal disease. We investigated how the sugar alcohol erythritol, which has anti-caries effects, impacts aging periodontal tissues and gingival fibroblasts in mice and humans in vivo and in vitro. Mice were classified into three groups: control groups of six-week-old (YC) and eighteen-month-old mice (AC) and a group receiving 5% w/w erythritol water for 6 months (AE). After rearing, RNA was extracted from the gingiva, and the levels of aging-related molecules were measured using PCR. Immunostaining was performed for the aging markers p21, γH2AX, and NF-κB p65. p16, p21, γH2AX, IL-1ß, and TNFα mRNA expression levels were higher in the gingiva of the AC group than in the YC group, while this enhanced expression was significantly suppressed in AE gingiva. NF-κB p65 expression was high in the AC group but was strongly suppressed in the AE group. We induced senescence in cultured human gingival fibroblasts using H2O2 and lipopolysaccharide before erythritol treatment, which reduced elevated senescence-related marker (p16, p21, SA-ß-gal, IL-1ß, and TNFα) expression levels. Knockdown of PFK or PGAM promoted p16 and p21 mRNA expression, but erythritol subsequently rescued pyruvate production. Overall, intraoral erythritol administration may prevent age-related oral mucosal diseases.

Long-Term Capsaicin Administration Ameliorates the Dysfunction and Astrogliosis of the Brain in Aged Mice with Missing Maxillary Molars.

Tooth loss and decreased masticatory function reportedly affect cognitive function; tooth loss allegedly induces astrogliosis and aging of astrocytes in the hippocampus and hypothalamus, which is a response specific to the central nervous system owing to homeostasis in different brain regions. Capsaicin, a component of red peppers, has positive effects on brain disorders in mice. Decreased expression of transient receptor potential vanilloid 1, a receptor of capsaicin, is associated with the development of dementia. In this study, we investigated the effect of capsaicin administration in aged mice (C57BL/6N mice) with reduced masticatory function owing to the extraction of maxillary molars to investigate preventive/therapeutic methods for cognitive decline attributed to age-related masticatory function loss. The results demonstrated that mice with impaired masticatory function showed decreased motor and cognitive function at the behavioral level. At the genetic level, neuroinflammation, microglial activity, and astrogliosis, such as increased glial fibrillary acidic protein levels, were observed in the mouse brain. The mice with extracted molars fed on a diet containing capsaicin for 3 months demonstrated improved behavioral levels and astrogliosis, which suggest that capsaicin is useful in maintaining brain function in cases of poor oral function and prosthetic difficulties.

The genome and genetics of a high oxidative stress tolerant Serratia sp. LCN16 isolated from the plant parasitic nematode Bursaphelenchus xylophilus.

BACKGROUND: Pine wilt disease (PWD) is a worldwide threat to pine forests, and is caused by the pine wood nematode (PWN) Bursaphelenchus xylophilus. Bacteria are known to be associated with PWN and may have an important role in PWD. Serratia sp. LCN16 is a PWN-associated bacterium, highly resistant to oxidative stress in vitro, and which beneficially contributes to the PWN survival under these conditions. Oxidative stress is generated as a part of the basal defense mechanism used by plants to combat pathogenic invasion. Here, we studied the biology of Serratia sp. LCN16 through genome analyses, and further investigated, using reverse genetics, the role of two genes directly involved in the neutralization of H2O2, namely the H2O2 transcriptional factor oxyR; and the H2O2-targeting enzyme, catalase katA. RESULTS: Serratia sp. LCN16 is phylogenetically most closely related to the phytosphere group of Serratia, which includes S. proteamaculans, S. grimessi and S. liquefaciens. Likewise, Serratia sp. LCN16 shares many features with endophytes (plant-associated bacteria), such as genes coding for plant polymer degrading enzymes, iron uptake/transport, siderophore and phytohormone synthesis, aromatic compound degradation and detoxification enzymes. OxyR and KatA are directly involved in the high tolerance to H2O2 of Serratia sp. LCN16. Under oxidative stress, Serratia sp. LCN16 expresses katA independently of OxyR in contrast with katG which is under positive regulation of OxyR. Serratia sp. LCN16 mutants for oxyR (oxyR::int(614)) and katA (katA::int(808)) were sensitive to H2O2 in relation with wild-type, and both failed to protect the PWN from H2O2-stress exposure. Moreover, both mutants showed different phenotypes in terms of biofilm production and swimming/swarming behaviors. CONCLUSIONS: This study provides new insights into the biology of PWN-associated bacteria Serratia sp. LCN16 and its extreme resistance to oxidative stress conditions, encouraging further research on the potential role of this bacterium in interaction with PWN in planta environment.

Catalases Induction in High Virulence Pinewood Nematode Bursaphelenchus xylophilus under Hydrogen Peroxide-Induced Stress.

Considered an EPPO A2 quarantine pest, Bursaphelenchus xylophilus is the causal agent of the pine wilt disease and the most devastating plant parasitic nematode attacking coniferous trees in the world. In the early stages of invasion, this nematode has to manage host defence mechanisms, such as strong oxidative stress. Only successful, virulent nematodes are able to tolerate the basal plant defences, and furthermore migrate and proliferate inside of the host tree. In this work, our main objective was to understand to what extent B. xylophilus catalases are involved in their tolerance to oxidative stress and virulence, using as oxidant agent the reactive oxygen species hydrogen peroxide (H2O2). After 24 hours of exposure, high virulence isolates of B. xylophilus could withstand higher H2O2 concentrations in comparison with low virulence B. xylophilus and B. mucronatus, corroborating our observation of Bxy-ctl-1 and Bxy-ctl-2 catalase up-regulation under the same experimental conditions. Both catalases are expressed throughout the nematode intestine. In addition, transgenic strains of Caenorhabditis elegans overexpressing B. xylophilus catalases were constructed and evaluated for survival under similar conditions as previously. Our results suggest that catalases of high virulence B. xylophilus were crucial for nematode survival under prolonged exposure to in vitro oxidative stress, highlighting their adaptive response, which could contribute to their success in host conditions.

Analysis of gene expression profiles of soft tissue sarcoma using a combination of knowledge-based filtering with integration of multiple statistics.

The diagnosis and treatment of soft tissue sarcomas (STS) have been difficult. Of the diverse histological subtypes, undifferentiated pleomorphic sarcoma (UPS) is particularly difficult to diagnose accurately, and its classification per se is still controversial. Recent advances in genomic technologies provide an excellent way to address such problems. However, it is often difficult, if not impossible, to identify definitive disease-associated genes using genome-wide analysis alone, primarily because of multiple testing problems. In the present study, we analyzed microarray data from 88 STS patients using a combination method that used knowledge-based filtering and a simulation based on the integration of multiple statistics to reduce multiple testing problems. We identified 25 genes, including hypoxia-related genes (e.g., MIF, SCD1, P4HA1, ENO1, and STAT1) and cell cycle- and DNA repair-related genes (e.g., TACC3, PRDX1, PRKDC, and H2AFY). These genes showed significant differential expression among histological subtypes, including UPS, and showed associations with overall survival. STAT1 showed a strong association with overall survival in UPS patients (logrank p = 1.84 × 10(-6) and adjusted p value 2.99 × 10(-3) after the permutation test). According to the literature, the 25 genes selected are useful not only as markers of differential diagnosis but also as prognostic/predictive markers and/or therapeutic targets for STS. Our combination method can identify genes that are potential prognostic/predictive factors and/or therapeutic targets in STS and possibly in other cancers. These disease-associated genes deserve further preclinical and clinical validation.

Pinewood nematode-associated bacteria contribute to oxidative stress resistance of Bursaphelenchus xylophilus.

BACKGROUND: Pine wilt disease (PWD) caused by the pinewood nematode Bursaphelenchus xylophilus is one of the most serious forest diseases in the world. The role of B. xylophilus-associated bacteria in PWD and their interaction with the nematode, have recently been under substantial investigation. Several studies report a potential contribution of the bacteria for the PWD development, either as a helper to enhance the pathogenicity of the nematode or as a pathogenic agent expressing interesting traits related to lifestyle host-adaptation. RESULTS: We investigated the nematode-bacteria interaction under a severe oxidative stress (OS) condition using a pro-oxidant hydrogen peroxide and explored the adhesion ability of these bacteria to the cuticle surface of the nematodes. Our results clearly demonstrated a beneficial effect of the Serratia spp. (isolates LCN-4, LCN-16 and PWN-146) to B. xylophilus under the OS condition. Serratia spp. was found to be extremely OS-resistant, and promote survival of B. xylophilus and down-regulate two B. xylophilus catalase genes (Bxy-ctl-1 and Bxy-ctl-2). In addition, we show that the virulent isolate (Ka4) of B. xylophilus survives better than the avirulent (C14-5) isolate under the OS condition. The bacterial effect was transverse for both B. xylophilus isolates. We could not observe a strong and specific adhesion of these bacteria on the B. xylophilus cuticle surface. CONCLUSIONS: We report, for the first time, that B. xylophilus associated bacteria may assist the nematode opportunistically in the disease, and that a virulent B. xylophilus isolate displayed a higher tolerance towards the OS conditions than an avirulent isolate.