ABSTRACT
The tumor microenvironment is an extremely complex composed of cancer cells and various non-cancer cells, including lymphatic endothelial cells. Lysophosphatidic acid (LPA) receptors (LPA1 to LPA6) activate a variety of malignant properties in human malignancies. In the present study, we examined the roles of LPA receptor-mediated signaling in biological responses of lymphatic endothelial SVEC4-10 cells induced by hypoxia. Lpar1, Lpar2 and Lpar3 expressions were decreased in SVEC4-10 cells cultured at hypoxic conditions (1 % O2). LPA had no impact on the cell growth activity of SVEC4-10 cells in 21 % O2 culture conditions. Conversely, the cell growth activity of SVEC4-10 cells in 1 % O2 culture conditions was reduced by LPA. The cell motile activity of SVEC4-10 cells was elevated by 1 % O2 culture conditions. GRI-977143 (LPA2 agonist) and (2S)-OMPT (LPA3 agonist) stimulated SVEC4-10 cell motility as well as AM966 (LPA1 antagonist). In tube formation assay, the tube formation of SVEC4-10 cells in 1 % O2 culture conditions was markedly increased, in comparison with 21 % O2. GRI-977143 and (2S)-OMPT elevated the tube formation of SVEC4-10 cells. Furthermore, the tube formation of SVEC4-10 cells was increased by AM966. These results suggest that LPA receptor-mediated signaling contributes to the modulation of hypoxic-induced biological functions of lymphatic endothelial cells.
Subject(s)
Cell Hypoxia , Cell Movement , Endothelial Cells , Lysophospholipids , Receptors, Lysophosphatidic Acid , Animals , Humans , Mice , Cell Line , Cell Movement/drug effects , Cell Proliferation/drug effects , Endothelial Cells/metabolism , Endothelial Cells/drug effects , Lysophospholipids/metabolism , Receptors, Lysophosphatidic Acid/metabolism , Receptors, Lysophosphatidic Acid/genetics , Signal Transduction , Lymphoid Tissue/cytology , Lymphoid Tissue/metabolismABSTRACT
In the tumor environment, hypoxia promotes tumor progression, such as cancer cell growth, migration and chemoresistance. This study aimed to evaluate the roles of free fatty acid receptors (FFARs) in the regulation of cancer cell functions under hypoxic conditions, using fibrosarcoma HT1080 cells. HT1080 cells expressed FFAR1, FFAR2 and FFAR3 genes, but not FFAR4 gene. FFAR1, FFAR2 and FFAR3 expression levels in HT1080 cells cultured at 1 % O2 were elevated, compared with 21 % O2. The cell growth activities of HT1080 cells cultured at 21 % O2 were inhibited by acetic acid (AA) and propanoic acid (PA), but not 1 % O2. HT1080 cell motility was markedly reduced by culturing at 1 % O2. The cell growth and motility of HT1080 cells were enhanced by FFAR2 knockdown. The cell viability to cisplatin (CDDP) of HT1080 cells cultured at 1 % O2 was increased, compared with 21 % O2. FFAR2 knockdown suppressed the cell viability to CDDP of HT1080 cells. On the other hand, the cell motility and viability to CDDP of HT1080 cells cultured at 21 % O2 were suppressed by TUG-770. When HT1080 cells were cultured at 1 % O2, the cell motility and viability to CDDP were decreased, correlating with FFAR1 expression level. Moreover, FFAR1 knockdown increased the cell viability to CDDP of HT1080 cells cultured at 1 % O2. These results suggest that FFAR-mediated signaling plays an important role in the modulation of cellular functions of HT1080 cells under hypoxic conditions.
Subject(s)
Fatty Acids, Nonesterified , Fibrosarcoma , Humans , Receptors, G-Protein-Coupled/metabolism , Cisplatin/pharmacology , Signal Transduction , Fibrosarcoma/metabolism , Cell MovementABSTRACT
The tumor microenvironment (TME) comprises cancer and non-cancerous stromal cells, including fibroblasts. Free fatty acids (FFAs) regulate various biological responses by binding to G protein-coupled FFA receptors (FFARs). In this study, we examined the impact of FFAR1 and FFAR4 on the cell migration of pancreatic cancer PANC-1 cells co-cultured with 3T3 fibroblast cells under hypoxic conditions. PANC-1 cells cultured at 1 % O2 exhibited elevated FFAR1 expression and decreased FFAR4 expression compared to those at 21 % O2. Cell migration of PANC-1 cells was reduced under 1 % O2 conditions. FFAR1 knockdown enhanced PANC-1 cell migration, whereas FFAR4 knockdown inhibited it. Co-culture of PANC-1 cells with 3T3 cells at 1 % O2 significantly increased FFAR4 expression, while FFAR1 expression remained unchanged. To evaluate the effects of FFAR1 and FFAR4 on PANC-1 cell migration in co-culture with 3T3 cells, we conducted a wound healing assay using the Culture-Insert 2 Well. PANC-1 and 3T3 cells were individually seeded into the two wells and incubated at both 21 % and 1 % O2 for 13 h. The cell migration of PANC-1 cells co-cultured with 3T3 cells at 1 % O2 was notably higher compared to 21 % O2. TUG-770 reduced and TUG-891 enhanced the cell migration of PANC-1 cells co-cultured with 3T3 cells under both 21 % and 1 % O2 conditions. These findings suggest that FFAR1 and FFAR4 play important roles in regulating the cell migration of PANC-1 cells co-cultured with 3T3 cells under hypoxic conditions.
Subject(s)
Cell Movement , Coculture Techniques , Fibroblasts , Pancreatic Neoplasms , Receptors, G-Protein-Coupled , Signal Transduction , Receptors, G-Protein-Coupled/metabolism , Receptors, G-Protein-Coupled/genetics , Pancreatic Neoplasms/pathology , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/genetics , Animals , Mice , Humans , Cell Line, Tumor , Fibroblasts/metabolism , Tumor Microenvironment , Cell Hypoxia , 3T3 CellsABSTRACT
The tumor microenvironment (TME) consists of various cell types, including fibroblasts. The TME plays a central role in the promotion of tumor progression. In the present study, we investigated whether lysophosphatidic acid (LPA) receptor-mediated signaling regulates cellular functions by the TME of pancreatic cancer PANC-1 cells. To obtain fibroblast 3T3 cell supernatants, 3T3 cells were cultured in 5% charcoal stripped FCS-DMEM for 48 h. LPAR2 and LPAR3 expression levels were elevated in PANC-1 cells cultured in 3T3 cell supernatants. While PANC-1 cell motility was decreased by 3T3 cell supernatants, the cell survival to cisplatin (CDDP) of PANC-1 cells was markedly enhanced. Moreover, the cell survival to CDDP of PANC-1 cells cultured in 3T3 cell supernatants was increased by GRI-977,143 (LPA2 agonist) and (2 S)-OMPT (LPA3 agonist). Since hypoxia is caused by the restriction of adequate vascular networks to deliver oxygen into solid tumors, PANC-1 cells were cultured in 3T3 cell supernatants at 1% O2 conditions. The cell survival to CDDP of PANC-1 cells cultured in 3T3 cell supernatants at 1% O2 was significantly elevated, correlating with LPAR2 and LPAR3 expressions. These results suggest that LPA signaling via LPA2 and LPA3 is involved in the promotion of malignant properties by the TME in PANC-1 cells.
Subject(s)
Pancreatic Neoplasms , Receptors, Lysophosphatidic Acid , Mice , Animals , Humans , Receptors, Lysophosphatidic Acid/metabolism , Lysophospholipids/metabolism , Lysophospholipids/pharmacology , Cisplatin/pharmacology , Fibroblasts/metabolism , Fibroblasts/pathology , Pancreatic Neoplasms/metabolism , Pancreatic Neoplasms/pathology , Cell Movement , Hypoxia/metabolism , Tumor Microenvironment , Pancreatic NeoplasmsABSTRACT
Linezolid (LZD) is an antimicrobial that is commonly used for treatment of vancomycin-resistant Enterococci and methicillin-resistant Staphylococcus aureus infections. However, the development of thrombocytopenia, one of the most frequent adverse side effects of this antimicrobial, can lead to discontinuation of LZD treatment. While clinical studies indicate that risk factors for the development of LZD-induced thrombocytopenia include treatment for >14 consecutive days, renal dysfunction, and chronic liver disease, the fundamental mechanism governing the pathogenesis of this disorder remains unclear. In this study, we aimed to elucidate the mechanism of LZD-induced thrombocytopenia by investigating the impact of LZD treatment on platelet destruction and production using rat platelet-rich plasma (PRP) and human immortalized cell lines, respectively. Compared to the control population, an increase in lactate dehydrogenase release was not detected upon exposure of rat PRP to varying concentrations of LZD, indicating that this compound is not cytotoxic towards platelets. Meanwhile, LZD treatment resulted in a significant dose-dependent increase in the proliferation of HEL human erythroleukemia and MEG-01 human megakaryoblast cells in vitro, but did not influence the differentiation of these cell lines. Lastly, LZD treatment yielded elevated levels of phosphorylation of myosin light chain 2 (MLC2), which regulates platelet release, in MEG-01 cells. Based on these results, we speculate that LZD induces thrombocytopenia by promoting MLC2 phosphorylation and thereby suppressing the release of platelets from mature megakaryocytes. These findings provide the first insight into the mechanism of LZD-mediated thrombocytopenia and may facilitate the development of strategies to treat and/or prevent this disease.
Subject(s)
Anti-Bacterial Agents/adverse effects , Blood Platelets/drug effects , Cardiac Myosins/metabolism , Linezolid/adverse effects , Myosin Light Chains/metabolism , Thrombocytopenia/metabolism , Animals , Blood Platelets/metabolism , Cell Differentiation/drug effects , Cell Line , Cell Line, Tumor , Cell Proliferation/drug effects , Humans , L-Lactate Dehydrogenase/metabolism , Male , Phosphorylation/drug effects , Rats, Wistar , Thrombocytopenia/chemically inducedABSTRACT
Background The purpose of this study was to clarify fading, red, green, and blue values (RGB) change, and color reproducibility for nipple-areola complex (NAC) tattoos. Methods NAC tattooing was performed on 60 sites in 59 Japanese patients prospectively. The evaluation was assessed using digital photo, Casmatch standardization, and RGB and luminance values preoperatively, immediately after, 1 week, 1, 3, 6, and 12 months after tattooing. RGB and luminance values changes over time, time-adjusted fading rate, and the rate of luminance at 12 months were calculated. In color reproducibility study ( n = 34), RGB values after 12 months were compared with the color sample about dark/reddish and light/less reddish pigments. Results RGB varied widely from immediately after to 1 month after tattooing. For RGB and luminance, significant differences were seen between pre and immediate after, 1 and 3 months, 3 and 6 months, and 6 and 12 months. In G values, significant differences were seen between all neighboring points. The fading rate tended to decrease as time progresses, but was not significant, that is, fading continued even between 6 and 12 months. Luminance was 9% brighter than contralateral NAC at 12 months. Color reproducibility tended to be higher with dark/reddish pigments, despite no significant differences. Conclusion The fading rate of tattooed NACs tended to decrease as time progresses, but fading still occurs between 6 and 12 months. Luminance was 9% brighter than contralateral NAC at 12 months after.
ABSTRACT
BACKGROUND: Tamoxifen (TAM) is a selective estrogen receptor modulator and has anti-estrogenic activity. Breast cancer cells acquire drug resistance to TAM as a consequence of long-term treatment. Lysophosphatidic acid (LPA) receptor-mediated signaling contributes to the promotion of tumor progression. This study aimed to evaluate the role of LPA receptors in the modulation of biological functions by long-term TAM treatment in breast cancer MCF-7 cells under hypoxic and estrogen-deprived conditions. METHODS: Long-term TAM treated (MCF-TAM) cells were generated from MCF-7 cells. Cells were cultured in estrogen-free medium at 1â¯% O2. LPA receptor expressions were measured by quantitative real-time RT-PCR analysis. Cell motile activity was investigated using Cell Culture Inserts. The CCK-8 kit was used to determine the cell proliferation rate. RESULTS: LPAR1 and LPAR3 expressions were elevated in MCF-TAM cells. MCF-TAM cell motility was enhanced by culturing at 1â¯% O2, compared with MCF-7 cells. When cells were cultured in estrogen-deprived medium at 1â¯% O2, the cell proliferation rate of MCF-TAM cells was significantly higher than that of MCF-7 cells. CONCLUSION: These results suggest that LPA receptor-mediated signaling plays an important role in the acquisition of malignant properties in long-term TAM treated MCF-7 cells under hypoxic and estrogen-deprived conditions.
Subject(s)
Antineoplastic Agents, Hormonal , Breast Neoplasms , Cell Movement , Cell Proliferation , Receptors, Lysophosphatidic Acid , Signal Transduction , Tamoxifen , Humans , Receptors, Lysophosphatidic Acid/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/metabolism , Breast Neoplasms/drug therapy , Tamoxifen/pharmacology , Signal Transduction/drug effects , MCF-7 Cells , Female , Cell Movement/drug effects , Cell Proliferation/drug effects , Antineoplastic Agents, Hormonal/pharmacology , Estrogens/metabolism , Estrogens/pharmacology , Cell Hypoxia/physiology , Cell Hypoxia/drug effectsABSTRACT
BACKGROUND: In the tumor environment, malignant characteristics of cancer cells are promoted by stromal cells under hypoxia. It is unknown whether lysophosphatidic acid (LPA) receptor-mediated signaling is involved in the regulation of cellular functions by endothelial cells in pancreatic cancer cells under hypoxic conditions. METHODS: Pancreatic cancer (PANC-1) cells were co-cultured with endothelial (F2) cells and F2 cell supernatants at 21% and 1% O2. The Cell Culture Insert was used to assess the cell motile activity. The cell growth and viability to cisplatin (CDDP) were measured, using the Cell Counting Kit-8. RESULTS: LPA receptor expression levels were changed in PANC-1 cells co-cultured with F2 cells at 21% and 1% O2. The cell motile activities of PANC-1 cells co-cultured with F2 cells at 21% and 1% O2 were markedly elevated, compared with PANC-1 cells alone. The cell viabilities to CDDP of PANC-1 cells co-cultured with F2 cell supernatants at 21% and 1% O2 were regulated by the activation of LPA receptors. CONCLUSION: These results suggest that LPA receptor-mediated signaling plays an important role in the modulation of pancreatic cancer cell functions by endothelial cells under hypoxic conditions.
Subject(s)
Endothelial Cells , Lysophospholipids , Pancreatic Neoplasms , Humans , Endothelial Cells/pathology , Receptors, Lysophosphatidic Acid/metabolism , Cell Movement , Cisplatin/pharmacology , Pancreatic Neoplasms/pathology , Hypoxia/metabolismABSTRACT
Lysophosphatidic acid (LPA) signaling via LPA receptors (LPA1 to LPA6) mediates various aspects of cancer cell behaviors. This study aimed to investigate the variation in intracellular ATP levels and its impact on cell viability in response to fluorouracil (5-FU) through LPA4 and LPA6 in colon cancer DLD-1 cells. LPA4 and LPA6 are linked to Gs and Gi proteins. Gs protein stimulates the activity of adenylyl cyclase, which catalyzes the conversion of ATP to cAMP, whereas Gi protein inhibits this activity. In cell survival assay, cells were treated with 5-FU every 24 h for 3 days. The viability in response to 5-FU in DLD-1 cells was enhanced by LPA4 and LPA6 knockdowns. Furthermore, LPA4 and LPA6 knockdowns reduced the expression of cleaved-PARP1 protein when cells were treated with 5-FU. Since ethidium bromide (EtBr) reduces mitochondrial DNA level in cultured cells, EtBr-treated (DLD-EtBr) cells were generated from DLD-1 cells. The viability to 5-FU in DLD-EtBr cells was higher than that of DLD-1 cells. Additionally, culturing DLD-1 cells in a low glucose-containing medium led to increased viability to 5-FU. LPAR4 and LPAR6 expressions were reduced in both DLD-EtBr and low glucose-treated cells. The cellular ATP levels were significantly decreased in DLD-1 cells following EtBr treatment and exposure to low glucose conditions. Conversely, in the presence of LPA, LPA4 and LPA6 knockdowns resulted in a marked elevation of ATP levels. These results suggest that cell viability to 5-FU is negatively regulated via the activation of LPA4-and LPA6-Gs protein pathways in DLD-1 cells rather than Gi protein.
ABSTRACT
Lysophosphatidic acid (LPA) binds to its specific G protein-coupled LPA receptors (LPA1 to LPA6), resulting in the activation of various cellular functions. LPA receptor-mediated signaling facilitates tumor progression in human malignancies. In the present study, we investigated whether LPA receptor-mediated signaling contributes to cellular responses to X-ray irradiation in osteosarcoma MG-63 cells. After X-ray irradiation (2, 4 and 8â¯Gy), LPAR2 and LPAR3 expression levels in MG-63 cells were significantly elevated in a dose-dependent manner, but no change of LPAR1 expression level was observed. The cell growth activities of MG-63 cells irradiated with X-rays (2, 4 and 8â¯Gy) were reduced by LPA. Conversely, LPA3 agonist (2â¯S)-OMPT enhanced the cell growth activities of X-ray irradiated MG-63 cells. The cell movement of MG-63 cells exposed to X-ray irradiation (8â¯Gy) was inhibited by (2â¯S)OMPT. In cell survival assay, (2â¯S)-OMPT suppressed the cell survival to cisplatin (CDDP) of MG-63 cells irradiated with X-rays (8â¯Gy). The cell survival to CDDP of X-ray irradiated cells was elevated by LPA3 knockdown. Moreover, we evaluated the effects of LPA2 on the cell survival to CDDP of MG-63 cells exposed to X-ray irradiation (8â¯Gy). The cell survival to CDDP of X-ray irradiated cells was increased by LPA2 agonist GRI-977143 and reduced by LPA2 knockdown. These results suggest that LPA receptor-signaling participates in the modulation of cellular functions induced by X-ray irradiation in osteosarcoma cells.
Subject(s)
Bone Neoplasms , Osteosarcoma , Receptors, Lysophosphatidic Acid , Humans , Bone Neoplasms/pathology , Bone Neoplasms/metabolism , Cell Line, Tumor , Cell Movement/drug effects , Cell Movement/radiation effects , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Lysophospholipids/pharmacology , Lysophospholipids/metabolism , Osteosarcoma/metabolism , Osteosarcoma/pathology , Osteosarcoma/radiotherapy , Receptors, Lysophosphatidic Acid/metabolism , Receptors, Lysophosphatidic Acid/radiation effects , Signal Transduction/drug effects , Signal Transduction/radiation effects , X-RaysABSTRACT
Background/purpose: Gum chewing has been found to improve oral function. Nevertheless, few randomized controlled trials have investigated the effects of gum-chewing exercises on oral function in older adults. This study aimed to examine the effect of gum-chewing exercises on oral function in older adults. Materials and methods: This was a single-blind, randomized controlled trial, conducted from November 2021 to January 2022. A total of 130 participants were divided randomly into the intervention and control groups. The intervention group was told to chew experimental gums for one month, while the control group was instructed to chew experimental tablets for one month. Maximum bite force, occlusal contact areas, oral dryness, tongue pressure, tongue and lip functions (number of times each of the following syllables is pronounced per second:/pa/,/ta/, and/ka/), masticatory function, subjective masticatory function, and gum-chewing time were measured at baseline and one month following intervention to assess outcomes. Results: One month following the intervention, tongue pressure was significantly higher in the intervention group than in the control group (P = 0.027). In the within-group comparisons, maximum bite force (P < 0.001), unstimulated saliva flow (P < 0.001), tongue and lip functions (/pa/: P < 0.001;/ta/: P < 0.001;/ka/: P < 0.001), color scale value (P = 0.019), and ΔE value (P = 0.024) were significantly increased in the intervention group. Conclusion: The results suggest that gum-chewing exercises can improve oral functions in older adults, although additional increases in masticatory load may be necessary to establish a more effective oral function training method using gum-chewing exercises in older adults.
ABSTRACT
BACKGROUND: Position of the nipple-areolar complex (NAC) is an important factor in the esthetic impression of the breast, and NAC malposition is often an issue in breast reconstruction after nipple-sparing mastectomy (NSM). The purpose of this study was to evaluate the degree of NAC malposition depending on several factors using data quantified with the Mamma Balance application (Medic Engineering K.K., Kyoto, Japan). METHODS: Patients who underwent unilateral breast reconstruction after NSM at eight hospitals in Japan between 2007 and 2020 were retrospectively investigated. Using Mamma Balance, NAC malposition was quantified separately in horizontal and vertical directions using patient photographs from pre-operatively and 6-24 months post-operatively. The degree of malpositioning was then statistically compared using various factors. RESULTS: The NAC deviated more cranially and medially with implants than that with flaps. Cases with latissimus dorsi flap showed lateral malposition more often than cases with deep inferior epigastric artery perforator flap. With flaps, lateral incisions showed more lateral malposition, and peri-areolar incisions tended to show more medial NAC malposition. In cases with severe post-operative infection of the implant, the NAC tended to deviate cranially. In radiation cases, the NAC deviated cranially. No significant difference was observed according to the degree of breast ptosis or use of the pull-down operation. Only a very weak correlation was observed between a larger amount of mastectomy and more cranial NAC malposition with both flaps and implants. CONCLUSIONS: This study provides insights into the tendencies and characteristics of NAC malposition.
Subject(s)
Breast Neoplasms , Mammaplasty , Mastectomy, Subcutaneous , Nipples , Humans , Female , Retrospective Studies , Nipples/surgery , Japan , Middle Aged , Mammaplasty/methods , Mammaplasty/adverse effects , Adult , Breast Neoplasms/surgery , Breast Neoplasms/pathology , Mastectomy, Subcutaneous/methods , Mastectomy, Subcutaneous/adverse effects , Aged , Postoperative Complications/etiology , Breast Implants/adverse effects , Surgical FlapsABSTRACT
Hydrogen peroxide (H2O2) is one of reactive oxygen species (ROS) and promotes malignant properties of cancer cells. Lysophosphatidic acid (LPA) signaling via LPA receptor (LPA1 to LPA6) regulates a variety of cellular functions, such as cell growth, migration and differentiation. This study aimed to evaluate the effects of LPA receptors on the cell motility and survival to anticancer drugs by H2O2 in colon cancer DLD-1 cells. To obtain H2O2 treated (DLD- H2O2) cells, cells were maintained in culture medium containing H2O2 (60 µM) for 2 months. LPAR2 and LPAR4 gene expressions were markedly elevated in DLD-H2O2 cells. The cell motility of DLD-H2O2 cells was significantly lower than that of DLD-1 cells. DLD-H2O2 cell motility was suppressed by LPA2 knockdown and stimulated by LPA4 knockdown. The cell survival rates to fluorouracil (5-FU), irinotecan (CPT-11) and oxaliplatin (L-OHP) of DLD-H2O2 cells were significantly higher than those of DLD-1 cells. The cell survival rate to 5-FU of DLD-H2O2 cells was decreased by LPA2 knockdown. Conversely, LPA4 knockdown enhanced the cell survival rate to 5-FU of DLD-H2O2 cells. In the tumor microenvironment, high levels of H2O2 production are observed under hypoxic conditions. The cell survival rate to 5-FU of DLD-H2O2 cells cultured at 1% O2 was significantly higher than that of DLD-1 cells cultured at 1% O2, correlating with LPAR2 gene expression. The present results suggest that the induction of LPA receptor-mediated signaling plays an important role in regulating cellular functions of DLD-1 cells treated with H2O2.
Subject(s)
Antineoplastic Agents , Neoplasms , Humans , Hydrogen Peroxide/pharmacology , Receptors, Lysophosphatidic Acid/genetics , Fluorouracil , Cell Movement , Antineoplastic Agents/pharmacologyABSTRACT
OBJECTIVES: To investigate crystallography, translucency, phase content, microstructure and flexural strength of two commercial strength-gradient multilayered dental zirconia grades. METHODS: Two zirconia grades, i.e., KATANA Zirconia YML (Kuraray Noritake; referred to as "YML"; composed of four layers: enamel, body 1-3) and IPS e.max ZirCAD Prime (Ivoclar Vivadent; referred to as "Prime"; composed of three layers: enamel, transition, body) were investigated. Fully sintered square-shaped zirconia specimens from each layer were prepared. Microstructure, chemical composition, translucency parameter and zirconia-phase composition of each layer were characterized. Four-point and biaxial flexural strength of each layer was measured using fully sintered bar- and square-shaped specimens. Square-shaped samples were used to measure strength across the layers. RESULTS: For both multilayer zirconia grades, the 'enamel' layer contains a higher amount of c-ZrO2, which resulted in higher translucency but lower flexural strength than the 'body' layers. The characteristic 4-point flexural strength of the YML 'body 2' (923 MPa) and 'body 3' (911 MPa) layers, and of the Prime 'body' (989 MPa) layer were comparable and higher than for the YML 'enamel' (634 MPa), Prime 'transition' (693 MPa) and 'enamel' (535 MPa) layers. The biaxial strength of specimens sectioned across the layers was in-between that of the 'enamel' and 'body' layers for both YML and Prime, implying the interfaces did not form a weak link. SIGNIFICANCE: The difference in yttria content affects the phase composition and mechanical properties of each layer of the multi-layer zirconia. The strength-gradient approach allowed to integrate monoliths with irreconcilable properties.
Subject(s)
Dental Materials , Zirconium , Dental Materials/chemistry , Materials Testing , Surface Properties , Zirconium/chemistry , Yttrium/chemistry , Ceramics/chemistryABSTRACT
This systematic review provides an update on the development and efficacy of direct restorative dental materials for root caries interventions from in vitro and clinical studies. PubMed, Embase, and Web of Science were searched using specific MeSH keywords. Full articles from September 1990 to October 2021 were collected. Additional articles were identified by reference retrieval and manual searching. Studies not related to restorative materials for root caries treatment, case reports, non-original articles, and/or articles not written in English were excluded. Bias risk assessment was performed for the clinical studies. Forty-two articles (eleven clinical studies and thirty-one in vitro studies) were included for analysis. Most in vitro studies indicated an excellent cariostatic effect of glass ionomer cement. Resin-modified glass ionomer restorations also presented reduced recurrent caries activity but had a lower efficacy than glass ionomer cement restorations. For composite resin restorations, the main material development strategies are to strengthen the tooth structure and integrate antimicrobial activity. The clinical studies offered limited data, so the most appropriate material for surface root caries treatment is still inconclusive. However, atraumatic restorative treatment (ART) is an alternative treatment for patients with limiting conditions. Further clinical studies are required to confirm the efficacy of bioactive materials.
ABSTRACT
There are numerous cultivars of tea (Camellia sinensis L.), but the differences in their anti-hyperglycemic-related effects are largely unknown. The inhibition of the dipeptidyl peptidase (DPP)-IV enzyme plays an essential role in controlling hyperglycemia in diabetes by blocking the degradation of incretin hormones, which is necessary for insulin secretion. In this study, we examined the DPP-IV inhibitory activity of leaf extracts from diverse Japanese green tea cultivars. The inhibitory rates differed among tea extracts. Metabolic profiling (MP), using liquid chromatography-mass spectrometry, of all cultivars revealed compositional differences among cultivars according to their DPP-IV inhibitory capacity. Epigallocatechin-3-O-(3-O-methyl)gallate, kaempferol-3-O-rutinoside, myricetin-3-O-glucoside/galactoside, and theogallin were newly identified as DPP-IV inhibitors. The bioactivity of a tea extract was potentiated by adding these ingredients in combination. Our results show that MP is a useful approach for evaluating the DPP-IV inhibitory potency of green tea and for determining bioactivity-related ingredients and combinations.
Subject(s)
Camellia sinensis , Dipeptidyl-Peptidase IV Inhibitors , Camellia sinensis/chemistry , Dipeptidyl Peptidase 4 , Dipeptidyl-Peptidase IV Inhibitors/chemistry , Metabolomics/methods , Plant Extracts/chemistry , Plant Extracts/pharmacology , Tea/chemistryABSTRACT
To develop antimicrobial restorative materials for root caries, we assessed a 4-META/MMA-TBB resin (Bondfill SB Plus, Sun Medical) containing benzalkonium chloride (BAC) or cetylpyridinium chloride (CPC) at 1.25, 2.5, and 5.0 wt%. The same resin without antibacterial agent was used as control. The degree of conversion was measured by attenuated total reflectance-Fourier transform infrared spectroscopy. The 3-point flexural strength test was conducted according to ISO 4049. The antimicrobial effect against three oral bacteria (Streptococcus mutans, S. sobrinus, and Actinomyces naeslundii) was assessed using agar diffusion tests. The shear bond strength to root dentin was assessed after 24 h of storage in water with or without 10,000 thermal cycles. The shear bond strength data were statistically compared using a linear mixed-effects model (α = 0.05). The specimen with 5.0 wt% BAC showed a significantly higher degree of conversion than the control, but it also had significantly lower flexural strength and lower shear bond strength after thermal cycling than the other specimens. When BAC or CPC was added at ≥ 2.5 wt%, the resins inhibited the growth of the three investigated microbes. In conclusion, both BAC and CPC showed significant antimicrobial effects when added at 5.0 wt% to the 4-META/MMA-TBB resin. Up to 2.5 wt%, neither antimicrobial agent affected the degree of conversion, flexural strength, or shear bond strength of the resin.
Subject(s)
Dental Bonding , Root Caries , Actinomyces , Anti-Bacterial Agents , Benzalkonium Compounds/pharmacology , Boron Compounds , Cetylpyridinium/pharmacology , Humans , Materials Testing , Methacrylates , Methylmethacrylates , Resin Cements , Tensile StrengthABSTRACT
Green tea, a widely consumed beverage in Asia, contains green tea catechins effective against obesity, especially epigallocatechin-3-O-gallate (EGCG), but must be consumed in an impractically huge amount daily to elicit its biological effect. Meanwhile, citrus polyphenols have various physiological effects that could enhance EGCG functionality. Here we investigated the antiobesity effect of a combination of EGCG and α-glucosyl hesperidin, a citrus polyphenol, at doses that have not been previously reported to exert antiobesity effects by themselves in any clinical trial. In a randomized, placebo-controlled, double-blinded, and parallel-group-designed clinical trial, 60 healthy Japanese males and females aged 30-75 years consumed green tea combined with α-glucosyl hesperidin (GT-gH), which contained 178 mg α-glucosyl hesperidin and 146 mg EGCG, for 12 weeks. Physical, hematological, blood biochemical, and urine examinations showed that GT-gH is safe to use. At week 12, GT-gH prevented weight gain and reduced body mass index (BMI) compared with the placebo. Especially in those aged < 50 years, triglyceride and body fat percentage decreased at week 6, visceral fat level and body fat percentage decreased at week 12; body weight, BMI, and blood LDL/HDL ratio also decreased. In conclusion, taking GT-gH prevents weight gain, and the antiobesity effect of GT-gH was more pronounced in people aged < 50 years.
Subject(s)
Catechin/analogs & derivatives , Glucosides/therapeutic use , Hesperidin/analogs & derivatives , Obesity/prevention & control , Tea , Adult , Body Mass Index , Catechin/administration & dosage , Catechin/therapeutic use , Female , Glucosides/administration & dosage , Hesperidin/administration & dosage , Hesperidin/therapeutic use , Humans , Male , Middle Aged , Placebos , Tea/chemistryABSTRACT
BACKGROUND: There are no reliable and validated objective biomarkers for the assessment of depression severity. We aimed to investigate the association between depression severity and timing-related speech features using speech recognition technology. METHOD: Patients with major depressive disorder (MDD), those with bipolar disorder (BP), and healthy controls (HC) were asked to engage in a non-structured interview with research psychologists. Using automated speech recognition technology, we measured three timing-related speech features: speech rate, pause time, and response time. The severity of depression was assessed using the Hamilton Depression Rating Scale 17-item version (HAMD-17). We conducted the current study to answer the following questions: 1) Are there differences in speech features among MDD, BP, and HC? 2) Do speech features correlate with depression severity? 3) Do changes in speech features correlate with within-subject changes in depression severity? RESULTS: We collected 1058 data sets from 241 individuals for the study (97 MDD, 68 BP, and 76 HC). There were significant differences in speech features among groups; depressed patients showed slower speech rate, longer pause time, and longer response time than HC. All timing-related speech features showed significant associations with HAMD-17 total scores. Longitudinal changes in speech rate correlated with changes in HAMD-17 total scores. CONCLUSIONS: Depressed individuals showed longer response time, longer pause time, and slower speech rate than healthy individuals, all of which were suggestive of psychomotor retardation. Our study suggests that speech features could be used as objective biomarkers for the assessment of depression severity.
Subject(s)
Bipolar Disorder/physiopathology , Depressive Disorder, Major/physiopathology , Speech , Artificial Intelligence , Case-Control Studies , Female , Humans , Male , Middle Aged , Time FactorsABSTRACT
Partial breast reconstruction using perforator flaps harvested from the lateral chest wall has become a well-established surgical technique recently. In the case of a partial mastectomy with an axillary lymph node dissection, there are 2 main defects; one is a partial breast defect and the other is an axillary dead space. To reconstruct the 2 separate defects with local flaps, basically 2 different flaps are needed, and usually, it is rather difficult to harvest 2 different local flaps in the adjacent area. To resolve this problem, we introduce the L-positioned perforator propeller flap (PPF). We used an L-positioned PPF on 2 female patients, aged 46 and 47 years old, who were suffering from breast cancer in the upper outer quadrant. The concept of this flap design is as follows: the partial breast defect is reconstructed with the longer lobe of the L-positioned PPF and the axillary defect is filled with the smaller lobe of the L-positioned PPF at the same time. The reconstruction time was 2 hours and 0 minutes and 1 hour and 46 minutes in each case. The patients were successfully provided with aesthetically acceptable breast reconstruction without postoperative complications. Moreover, both patients had consecutive postoperative radiotherapy on the reconstructed area without complications. With this flap design, it is possible for patients to have safe and aesthetic reconstruction with only 1 local flap and fewer invasive procedures.