Hyperthermia maintains death receptor expression and promotes TRAIL-induced apoptosis.

BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand activates apoptotic pathways and could potentially be used in anticancer treatments. However, oral squamous cell carcinoma cells are known to be resistant to tumor necrosis factor-related apoptosis-inducing ligand-induced cell death. It has been previously reported that hyperthermia upregulates tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in other cancers. As such, we evaluated whether hyperthermia upregulates tumor necrosis factor-related apoptosis-inducing ligand-mediated apoptosis in a tumor necrosis factor-related apoptosis-inducing ligand-resistant oral squamous cell carcinoma cell line. METHODS: The oral squamous cell carcinoma cell line HSC3 was cultured and divided into hyperthermia and control groups. We investigated the antitumor effects of recombinant human tumor necrosis factor-related apoptosis-inducing ligand using cell proliferation and apoptosis assays. Additionally, we measured death receptor 4 and 5 levels, and determined death receptor ubiquitination status, as well as E3 ubiquitin ligase targeting of death receptor in both hyperthermia and control groups before recombinant human tumor necrosis factor-related apoptosis-inducing ligand administration. RESULTS: Treatment with recombinant human tumor necrosis factor-related apoptosis-inducing ligand produced greater inhibitory effects in the hyperthermia group than in the control group. Moreover, death receptor protein expression in the hyperthermia group was upregulated on the cell surface (and overall), although death receptor mRNA was downregulated. The half-life of death receptor was several hours longer in the hyperthermia group; concomitantly, E3 ubiquitin ligase expression and death receptor ubiquitination were downregulated in this group. CONCLUSION: Our findings suggested that hyperthermia enhances apoptotic signaling by tumor necrosis factor-related apoptosis-inducing ligand via the suppression of death receptor ubiquitination, which upregulates death receptor expression. These data suggest that the combination of hyperthermia and tumor necrosis factor-related apoptosis-inducing ligand has implications in developing a novel treatment strategy for oral squamous cell carcinoma.

Family with sequence similarity 20 member B regulates osteogenic differentiation of bone marrow mesenchymal stem cells on titanium surfaces.

Successful bone regeneration on titanium (Ti) surfaces is a key process in dental implant treatment. Bone marrow mesenchymal stem cells (BMSCs) are fundamental cellular components of this process, and their early recruitment, proliferation, and differentiation into bone-forming osteoblasts are crucial. A proteoglycan (PG)-rich layer has been reported to exist between Ti surfaces and bones; however, the molecules that could potentially affect the formation of this layer remain unknown. Family with sequence similarity 20 member B (FAM20B) is a newly identified kinase that regulates the synthesis of glycosaminoglycans, an important component of the PG-rich layer. Because FAM20B is also closely associated with bone development, in this study, we examined the function of FAM20B in osteogenic differentiation of BMSCs on Ti surfaces. For this, BMSC cell lines with knocked down FAM20B (shBMSCs) were cultured on Ti surfaces. The results showed that the depletion of FAM20B reduced the formation of a PG-rich layer between the Ti surfaces and cells. The shBMSCs exhibited downregulated expression of osteogenic marker genes (ALP and OCN) and decreased mineral deposition. Moreover, shBMSCs reduced the molecular levels of p-ERK1/2, which plays an important role in MSC osteogenesis. The nuclear translocation of RUNX2, an important transcription factor for osteogenic differentiation, on the Ti surfaces is inhibited by the depletion of FAM20B in BMSCs. Moreover, the depletion of FAM20B reduced the transcriptional activity of RUNX2, which is important in regulating the expression of osteogenic genes. STATEMENT OF SIGNIFICANCE: Bone healing and regeneration on implanted titanium surfaces is a cell-material interaction. Such an interaction is enabled by bone marrow mesenchymal stem cells (BMSCs), and their early recruitment, proliferation, and differentiation into bone-forming osteoblasts are essential for bone healing and osseointegration. In this study, we found that the family with sequence similarity 20-B influenced the formation of a proteoglycan rich layer between BMSCs and the titanium surface and regulated the differentiation of BMSCs into bone-forming osteoblasts. We believe that our study contributes significantly to the further exploration of bone healing and osseointegration mechanisms on implanted titanium surfaces.

Efficacy of semi-solidification of enteral nutrients for postoperative nutritional management with a nasogastric tube.

Postoperative nutritional management with a nasogastric tube is often used to prevent malnutrition after oral and maxillofacial surgery. However, enteral nutrients (EN) may cause various complications due to their liquid formulation. In this study, we retrospectively evaluated the efficacy of semi-solid EN with a xanthan gum thickener through a nasogastric tube and examined patients' complications, nutritional status, and quality of life. We established two groups: an L group (n=20) to which we administered liquid EN, and an SS group (n=20) to which we administered semi-solidified EN. The primary outcome was the occurrence of gastrointestinal complications. The secondary outcome was a change in nutritional status based on body weight and controlling nutritional status. The other outcome was the improvement in the patients' quality of life, assessed by the administration time. During nutritional management with a nasogastric tube, the median daily administration time in the L group was 9.0 hours, and 9 patients experienced diarrhea. In the SS group, the median daily feeding time was 2.3 hours, and only 2 patients experienced diarrhea. Both groups exhibited a decrease in body weight while controlling nutritional status scores were maintained. Semi-solidification of EN may be useful for postoperative nutritional management after oral and maxillofacial surgery by reducing complications, maintaining nutritional status, and shortening administration time.

Anagliptin, a dipeptidyl peptidase-4 inhibitor, improved bladder function and hemodynamics in rats with bilateral internal iliac artery ligation.

AIMS: To investigate the effect of anagliptin (Ana), a dipeptidyl peptidase-4 (DPP-4) inhibitor, on acute ischemia-induced bladder dysfunction in rats. METHODS: Eight-week-old female Wistar-ST rats were randomly assigned into four groups: (a) sham; (b) ligation (Lig); (c) Lig + Ana; and (d) Lig + Liraglutide (a glucagon-like peptide-1 [GLP-1] receptor agonist; Lira). Rats in the Lig, Lig + Ana, and Lig + Lira groups underwent ligature of the bilateral internal iliac arteries. Ana was orally administered mixed with the CE-2 diet. Lira was subcutaneously administered once a day. Blood glucose levels, plasma dipeptidyl peptidase 4 (DPP-4) activity, GLP-1 levels, and bladder function were measured in all groups. Bladder blood flow was measured in the sham, Lig, and Lig + Ana groups, 4 weeks postsurgery. RESULTS: No differences in blood glucose levels among the groups were observed. DPP-4 activity decreased in the Lig + Ana group (P < .01). GLP-1 levels in the Lig + Ana and Lig + Lira groups were higher than those in the sham and Lig groups (P < .01). Intercontraction intervals (ICIs) were longer in the Lig and Lig + Lira groups than in the sham group (P < .05), but similar to those observed in the Lig + Ana and sham groups. The Lig group exhibited reduced bladder blood flow relative to the sham group (P < .01); however, this measure improved in the Lig + Ana group (P < .01). CONCLUSIONS: Ana administration improved ICIs and bladder blood flow after acute bladder ischemia through a GLP-1 receptor-independent signaling pathway, without altering the blood glucose levels. Therefore, Ana dosing might be useful to prevent ischemia-induced bladder dysfunctions.

Chondroitin-4-sulfate transferase-1 depletion inhibits formation of a proteoglycan-rich layer and alters immunotolerance of bone marrow mesenchymal stem cells on titanium oxide surfaces.

Successful osseointegration is essential for dental implants. However, the complete molecular mechanism of osseointegration remains to be elucidated. In this study, we focused on the proteoglycan (PG)-rich layer between titanium oxides (TiOx) and bone, and chondroitin-4-sulfate transferase-1 (C4ST-1), which forms the sugar chain in PGs. Human bone marrow mesenchymal stem cells (hBMSCs) depleted of C4ST-1 were cultured on titanium (Ti) plates, and the interface between hBMSCs and TiOx was analyzed using transmission electron microscopy. Immunotolerance, proliferation, initial adhesion, and calcification of the cells were analyzed in vitro. At 14 days of cultivation, a PG-rich layer was observed between hBMSCs and TiOx. However, the PG-rich layer was reduced in C4ST-1-depleted hBMSCs on TiOx. Real-time RT-PCR showed that conditioned media increased the levels of expression of M1-macrophage markers in human macrophages. However, depletion of C4ST-1 did not affect calcification, cell proliferation, or initial cell adhesion on Ti plates. These results suggested that C4ST-1 in hBMSCs affects their immunotolerance and alters the formation of PG-rich layer formation on TiOx.

Differences in xylem development between Dutch and Japanese tomato (Solanum lycopersicum) correlate with cytokinin levels in hypocotyls.

BACKGROUND AND AIMS: Dutch tomato cultivars tend to have a greater yield than Japanese cultivars even if they are grown under the same conditions. Factors contributing to the increased yield of the Dutch cultivars were a greater light use efficiency and greater leaf photosynthetic rate. On the other hand, the relationship between tomato yields and anatomical traits is still unclear. The aim of this study is to identify the anatomical traits related to the difference in yield between Dutch and Japanese cultivars. METHODS: Anatomical properties were compared during different growth stages of Dutch and Japanese tomatoes. Hormone profiles and related gene expression in hypocotyls of Dutch and Japanese cultivars were compared in the hypocotyls of 3- and 4-week-old plants. KEY RESULTS: Dutch cultivars have a more developed secondary xylem than Japanese cultivars, which would allow for greater transport of water, mineral nutrients and phytohormones to the shoots. The areas and ratios of the xylem in the hypocotyls of 3- to 6-week-old plants were larger in the Dutch cultivars. In reciprocal grafts of the Japanese and Dutch cultivars, xylem development at the scion and rootstock depended on the scion cultivar, suggesting that some factors in the scion are responsible for the difference in xylem development. The cytokinin content, especially the level of N6-(Δ 2-isopentenyl) adenine (iP)-type cytokinin, was higher in the Dutch cultivars. This result was supported by the greater expression of Sl-IPT3 (a cytokinin biosynthesis gene) and Sl-RR16/17 (a cytokinin-responsive gene) in the Dutch cultivars. CONCLUSIONS: These results suggest that iP-type cytokinins, which are locally synthesized in the hypocotyl, contribute to xylem development. The greater xylem development in Dutch cultivars might contribute to the high yield of the tomato.