Suppression of cell cycle progression by Jun dimerization protein (JDP2) involves down-regulation of cyclin A2

We report here a novel role for Jun dimerization protein-2 (JDP2) as a regulator of the progression of normal cells through the cell cycle. To determine the role of JDP2 in vivo, we generated Jdp2 knock-out (Jdp2KO) mice by targeting exon 1 to disrupt the site of initiation of transcription. The healing of wounded skin of Jdp2KO mice proceeded more rapidly than that of control mice and more proliferating cells were found at wound margins. Fibroblasts derived from embryos of Jdp2KO mice proliferated more rapidly and formed more colonies than wild-type fibroblasts. JDP2 was recruited to the promoter of the gene for cyclin A2 (ccna2) at a previously unidentified AP-1 site. Cells lacking Jdp2 had elevated levels of cyclin A2 mRNA. Moreover, reintroduction of JDP2 resulted in repression of transcription of ccna2 and of cell cycle progression. Thus, transcription of the gene for cyclin A2 appears to be a direct target of JDP2 in the suppression of cell proliferation

Capsicum ethanol extracts and capsaicin enhance interleukin-2 and interferon-gamma production in cultured murine Peyer\u27s patch cells ex vivo

金沢大学大学院自然科学研究科生理活性物質科学金沢大学薬学部We investigated the effects of red pepper (Capsicum annuum Lin.) extracts (capsicum extract) and its main pungent capsaicin on T helper 1 (Th1) and 2 (Th2) cytokine production in cultured murine Peyer\u27s patch (PP) cells in vitro and ex vivo. Direct administration of capsicum extract (1 and 10 μg/ml) and capsaicin (3 and 30 μM) resulted in suppression of interleukin (IL)-2, interferon (IFN)-γ, IL-4 and IL-5 production. In an ex vivo experiment using PP cells removed from the mice after oral administration of capsicum extract (10 mg/kg/day for 4 consecutive days), IL-2, IFN-γ and IL-5 increased in response to concanavalin A (Con A). Oral administration of 3 mg/kg/day capsaicin, one active constituent of the extract, also enhanced IL-2, INF-γ and IL-4 production in response to Con A stimulation but did not influence the production of IL-5. Orally administered capsazepine (3 mg/kg/day), a selective transient receptor potential vanilloid 1 (TRPV1) antagonist, slightly enhanced IL-2 production also irrespective of Con A stimulation. The capsaicin-induced enhancement of both IL-2 and IFN-γ production was not reduced by oral administration of capsazepine (3 mg/kg/day), suggesting a TRPV1 receptor-independent mechanism. Flow cytometric analysis revealed that the population of CD3+ cells in the PP cells was significantly reduced while CD19+ cells increased after oral administration of capsicum extract (1 and 10 mg/kg/day) and capsaicin (0.3 and 3 mg/kg/day). Capsazepine (3 mg/kg/day) weakly but significantly reversed these effects. Orally administered capsicum extract and capsaicin did not change the T cell subset (CD4+ and CD8+), Th1 (IFN-γ+) and T2 (IL-4+) ratio. These findings indicate that capsicum extract and capsaicin modulate T cell-immune responses, and their immunomodulatory effects on murine PP cells are partly due to both TRPV1-dependent and -independent pathway. © 2007 Elsevier Inc. All rights reserved

Sox21 Regulates Anapc10 Expression and Determines the Fate of Ectodermal Organ

The transcription factor Sox21 is expressed in the epithelium of developing teeth. The present study aimed to determine the role of Sox21 in tooth development. We found that disruption of Sox21 caused severe enamel hypoplasia, regional osteoporosis, and ectopic hair formation in the gingiva in Sox21 knockout incisors. Differentiation markers were lost in ameloblasts, which formed hair follicles expressing hair keratins. Molecular analysis and chromatin immunoprecipitation sequencing indicated that Sox21 regulated Anapc10, which recognizes substrates for ubiquitination-mediated degradation, and determined dental-epithelial versus hair follicle cell fate. Disruption of either Sox21 or Anapc10 induced Smad3 expression, accelerated TGF-beta 1-induced promotion of epithelial-to-mesenchymal transition (EMT), and resulted in E-cadherin degradation via Skp2. We conclude that Sox21 disruption in the dental epithelium leads to the formation of a unique microenvironment promoting hair formation and that Sox21 controls dental epithelial differentiation and enamel formation by inhibiting EMT via Anapc10.Peer reviewe

Importance of feeding status evaluation in older patients undergoing hemodialysis

Older hospitalized patients undergoing hemodialysis are increasingly experiencing malnutrition caused by dysphagia. However, only a few studies have focused on this problem. We used the Kuchikara Taberu Balance Chart (KTBC) to evaluate the patients’ feeding status and examined its association with their nutritional status and prognosis. This study included elderly patients undergoing hemodialysis who were hospitalized at Nagasaki Renal Center for > 3 days between June 2021 and February 2022. In total, 82 inpatients were included [mean age, 73.4 ± 10.0 years; men, 57.3%; median dialysis vintage, 79.0 months (interquartile range, 37.3–164.8)]. We classified patients with lower than the median KTBC score (57 points) as being at risk for dysphagia; 37 patients (45.1%) were at risk for dysphagia. Spearman’s rank correlation coefficient (ρ) elucidated that the KTBC total score was significantly associated with each nutritional indicator [serum albumin level (ρ = 0.505, p < 0.001); geriatric nutritional risk index (ρ = 0.600, p < 0.001); and nutritional risk index (ρ = -0.566, p < 0.001)]. The KTBC score was also closely associated with the body mass index (ρ = 0.228, p = 0.04). Patients with a lower KTBC score showed poor prognosis (log-rank test: p = 0.001), and age- and sex-adjusted Cox proportional analysis showed that the KTBC score was associated with life prognosis (hazard ratio, 0.90; 95% confidential interval, 0.86–0.94; p < 0.001). Therefore, we concluded that the patients at risk of dysphagia, identified using the KTBC score, were malnourished and had a poor prognosis. Hence, the evaluation of dysphagia using the KTBC is encouraged to prevent malnutrition in vulnerable older patients undergoing hemodialysis

The impact of muscle mass loss and deteriorating physical function on prognosis in patients receiving hemodialysis

Muscle mass loss and worsening physical function are crucial issues in patients receiving hemodialysis (HD). However, few studies have investigated the association between temporal changes in muscle mass and physical function in a large number of HD patients. We examined 286 patients receiving HD (males, 58%; age, 66.8 ± 13.0 years) at a single center, and calculated the percent changes in psoas muscle mass index (%PMI) using computed tomography over two screenings, once per year (July 2011–June 2013). Physical function was evaluated using the Eastern Cooperative Oncology Group Performance Status (ECOG-PS) (range 0–4). The observation period was from July 2012 to June 2021. The median %PMI was -9.5%, and those with the lowest quartile of %PMI (< −20.5%) showed a significantly poor prognosis compared with other patients (p < 0.001). Multivariable logistic regression analysis revealed that these patients tended to have decreased physical function (ECOG-PS 2–4) [odds ratio (OR): 2.46, p < 0.001] and albumin levels (OR: 0.22, p = 0.007). Multiple-factor-adjusted Cox regression analyses showed that %PMI (hazard ratio: 0.99, p = 0.004) and each ECOG-PS stage (1–4 vs. 0) (p < 0.01) were associated with mortality. Augmenting physical activities in daily life and serum albumin levels should be considered to maintain muscle mass and improve the prognosis of patients receiving HD

Dram1 regulates DNA damage-induced alternative autophagy

Autophagy is an evolutionarily conserved process that degrades subcellular constituents. Mammalian cells undergo two types of autophagy; Atg5-dependent conventional autophagy and Atg5-independent alternative autophagy, and the molecules required for the latter type of autophagy are largely unknown. In this study, we analyzed the molecular mechanisms of genotoxic stress-induced alternative autophagy, and identified the essential role of p53 and damage-regulated autophagy modulator (Dram1). Dram1 was sufficient to induce alternative autophagy. In the mechanism of alternative autophagy, Dram1 functions in the closure of isolation membranes downstream of p53. These findings indicate that Dram1 plays a pivotal role in genotoxic stress-induced alternative autophagy

Association between the psoas muscle index and hospitalization for pneumonia in patients undergoing hemodialysis

Background: Although muscle mass loss and pneumonia are common and crucial issues in hemodialysis (HD) patients, few reports have focused on their association, which remains unclear. This study assessed the association between skeletal muscle mass and the incidence of pneumonia in HD patients using the psoas muscle index (PMI).Methods: This retrospective study included 330 patients on HD who were treated at a single center between July 2011 and June 2012. The observation period was between July 2011 and June 2021. Demographic, clinical, and HD data were collected, and the associations between PMI and hospitalization due to bacterial pneumonia were evaluated using Cox proportional hazards models adjusted for patients’ background data. Additionally, the correlation between patient characteristics and PMI was evaluated using multivariable linear regression.Results: Among 330 patients (mean age, 67.3 ± 13.3; 56.7% male; median dialysis vintage 58 months, (interquartile range [IQR] 23–124), 79 were hospitalized for pneumonia during the observation period (median observation period was 4.5 years [IQR 2.0–9.1]). The multivariable Cox proportional analysis, which was adjusted for age, sex, dialysis vintage, diabetes mellitus, and stroke history and considered death as a competing risk, indicated that decreased PMI/(standard deviation) was closely associated with the development of pneumonia (hazard ratio: 0.67, 95% confidence interval: 0.47–0.95, p = 0.03).Conclusions: Skeletal muscle mass was associated with the development of pneumonia in patients on HD and could be a useful marker for the risk of pneumonia