Sessile serrated adenoma/polyp-cancer sequenceにおいてS100Pは遺伝子脱メチル化により発現し、細胞増殖を促進する

Background/Aims: Sessile serrated adenomas/polyps (SSA/Ps) are a putative precursor lesion of colon cancer. Although the relevance of DNA hypermethylation in the SSA/P-cancer sequence is well documented, the role of DNA hypomethylation is unknown. We investigated the biological relevance of DNA hypomethylation in the SSA/P-cancer sequence by using 3-dimensional organoids of SSA/P. Methods: We first analyzed hypomethylated genes using datasets from our previous DNA methylation array analysis on 7 SSA/P and 2 cancer in SSA/P specimens. Expression levels of hypomethylated genes in SSA/P specimens were determined by RT-PCR and immunohistochemistry. We established 3-dimensional SSA/P organoids and performed knockdown experiments using a lentiviral shRNA vector. DNA hypomethylation at CpG sites of the gene was quantitated by MassARRAY analysis. Results: The mean number of hypomethylated genes in SSA/P and cancer in SSA/P was 41.6 ± 27.5 and 214 ± 19.8, respectively, showing a stepwise increment in hypomethylation during the SSA/P-cancer sequence. S100P, S100α2, PKP3, and MUC2 were most commonly hypomethylated in SSA/P specimens. The mRNA and protein expression levels of S100P, S100α2, and MUC2 were significantly elevated in SSA/P compared with normal colon tissues, as revealed by RT-PCR and immunohistochemistry, respectively. Among these, mRNA and protein levels were highest for S100P. Knockdown of the S100P gene using a lentiviral shRNA vector in 3-dimensional SSA/P organoids inhibited cell growth by >50% (p < 0.01). The mean diameter of SSA/P organoids with S100P gene knockdown was significantly smaller compared with control organoids. MassARRAY analysis of DNA hypomethylation in the S100P gene revealed significant hypomethylation at specific CpG sites in intron 1, exon 1, and the 5′-flanking promoter region. Conclusion: These results suggest that DNA hypomethylation, including S100P hypomethylation, is supposedly associated with the SSA/P-cancer sequence. S100P overexpression via DNA hypomethylation plays an important role in promoting cell growth in the SSA/P-cancer sequence

Exploring the association between number of teeth, food intake, and cognitive function: A 9-year longitudinal study

Mameno T., Moynihan P., Nakagawa T., et al. Exploring the association between number of teeth, food intake, and cognitive function: A 9-year longitudinal study. Journal of Dentistry 145, 104991 (2024); https://doi.org/10.1016/j.jdent.2024.104991.Objectives: This study aimed to investigate the association between the number of teeth, food intake, and cognitive function in Japanese community-dwelling older adults. Methods: This 9-year longitudinal study included a total of 293 analyzable participants who participated in baseline and follow-up surveys. Dental status (number of teeth and periodontal pocket depth), dietary assessment using the brief-type self-administered diet history questionnaire, cognitive function, and the following confounding factors were evaluated: educational level, financial satisfaction, living situation, smoking and drinking habits, history of chronic diseases, apolipoprotein E-ε4 carrier, body mass index, handgrip strength, instrumental activities of daily living, and depressive symptomatology. The Japanese version of the Montreal Cognitive Assessment was used to evaluate cognitive function. A multinomial logistic regression analysis for the intake level of each food categorized into three groups (low, moderate, high), and a generalized estimating equation (GEE) for cognitive function over nine years were performed. Results: After controlling for confounding factors, the number of teeth was shown to be associated with the intake of green-yellow vegetables and meat. Furthermore, the GEE indicated that the lowest quartile of intake of green-yellow vegetables significantly associated with lower cognitive function (unstandardized regression coefficient [B] = -0.96, 95 % confidence interval [CI]: -1.72 to -0.20), and the lowest quartile of intake of meat significantly associated with lower cognitive function (B = -1.42, 95 % CI: -2.27 to -0.58). Conclusions: The intake of green and yellow vegetables and meat, which is influenced by the number of teeth, was associated with cognitive function in Japanese community-dwelling older adults. Clinical Significance: There are few studies that have examined the association between oral health, food intake, and cognitive function. This 9-year longitudinal study suggests that it is important to maintain natural teeth to enable the functional means to consume green-yellow vegetables and meat, and thereby help maintain cognitive function

Review Article : Feudalism or Absolute Monarchism?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/68809/2/10.1177_009770049001600304.pd

精巣平滑筋腫の1例

A case of leiomyoma of the testis is reported. The origin of the intratesticular leiomyoma is controversial, but recently it is thought to arise from the contractile cells in the tunica propria of the seminiferous tubules. This is the first case reported in Japan and the fifth in the world literature

Risk factors of cognitive impairment: Impact of decline in oral function

Cognitive impairment and subsequent dementia are the major causes of disability and need for nursing care among older people in worldwide. The purpose is to review well-known risk factors for cognitive impairment and dementia, focusing on the relationship between decline in oral function and current prevention strategies. Various non-modifiable and modifiable risk factors are related to cognitive impairment. Effects of oral function to cognitive impairment is not yet well recognized in the medical community, although masticatory function, occlusal force, and number of teeth have been reported to be related to cognitive function. Furthermore, occlusal force rather than number of teeth was significantly related to the early stages of cognitive impairment, and that a decline in occlusal force seemed to lead to cognitive impairment directly and indirectly through dietary intake. This relationship was significant only for occlusal force, which may be associated with the early stages of cognitive decline. Nutritional change caused by reduced masticatory function is suggested as a possible explanation. Therefore, rehabilitation or maintenance of oral function should be sought to prevent cognitive impairment

Hybrid thoracic endovascular aortic repair of ascending aortic pseudoaneurysm

We report the successful thoracic endovascular aortic repair of an ascending aortic pseudoaneurysm. Because the risk of resternotomy after conventional surgery was very high, endovascular repair with extra-anatomic reconstruction of the supra-aortic vessels was performed using the femoral artery as the donor artery. Complete exclusion of the pseudoaneurysm was achieved, with no postoperative complications or neurologic sequelae

Factors Related to Preventive Behaviors against a Decline in Physical Fitness among Community-Dwelling Older Adults during the COVID-19 Pandemic: A Qualitative Study

Older adults face the concern of developing frailty and sarcopenia due to an inactive lifestyle during the coronavirus disease 2019 (COVID-19) pandemic. This study aimed to reveal the preventive behaviors taken by older adults who perceived a decline in physical fitness during COVID-19 and analyze the background factors which promoted such behaviors using a qualitative study design in 2020. The participants were recruited through the cohort study of Japanese older adults who were aged 79&ndash;81 and had not been diagnosed with sarcopenia previously in 2019 and perceived their physical fitness to have declined during the pandemic. The interviews of 19 participants were analyzed using thematic analysis. The participants engaged in five types of preventive behaviors to counter declining physical fitness: &ldquo;walking&rdquo;, &ldquo;exercising at home&rdquo;, &ldquo;improving daily diet&rdquo;, &ldquo;maintaining a daily routine&rdquo;, and &ldquo;taking a good rest&rdquo;. Four themes were extracted pertaining to backgrounds of such preventive behaviors: &ldquo;feeling anxiety and mental pressure&rdquo;, &ldquo;available networks with family and neighbors&rdquo;, &ldquo;prior experiences of behaviors&rdquo;, and &ldquo;access to information&rdquo;. Anxiety due to lifestyle changes during the pandemic was the primary reason for the behaviors. This study can be a useful guide for undertaking possible measures to prevent frailty during future pandemics