Purpose: This study aimed to develop an animal model suitable for coronectomy research. Materials and Methods: Eighteen Sprague-Dawley rats were divided into six groups: incisor control (InC), incisor flap (InF), incisor non-flap (InNF), molar control (MC), molar flap (MF), and molar non-flap (MNF). Coronectomy was not performed in the control groups (InC and MC). In the incisor (In) groups, coronectomy was performed on the mandibular incisors, with flap elevation in the InF group and without flap elevation in the InNF group. In the molar (M) groups, coronectomy was performed on the maxillary first molar, with flap elevation in the MF group and without flap elevation in the MNF group. The incisor groups were sacrificed on day 7, and the molar groups on days 7 and 14. Clinical healing, tooth movement, and histological and immunohistochemical analyses were performed. Results: InF and InNF groups showed tooth eruption similar to or the same as that before coronectomy, whereas the MF and MNF groups’ roots moved slowly. In InF and InNF groups, the pulp at the maturation zone was mineralized, but apical pulp vitality was maintained. MF and MNF groups showed bacterial infection and inflammation on day 7, with mineralization on day 14; however, apical pulp vitality was maintained. The MF group showed varied healing patterns, whereas the MNF group had consistent results across individuals. Conclusion Both incisors and molars are meaningful models for coronectomy. However, for consistent experimental results, coronectomy without flap elevation on the maxillary first molar is recommended.

Purpose: This study aimed to develop an animal model suitable for coronectomy research. Materials and Methods: Eighteen Sprague-Dawley rats were divided into six groups: incisor control (InC), incisor flap (InF), incisor non-flap (InNF), molar control (MC), molar flap (MF), and molar non-flap (MNF). Coronectomy was not performed in the control groups (InC and MC). In the incisor (In) groups, coronectomy was performed on the mandibular incisors, with flap elevation in the InF group and without flap elevation in the InNF group. In the molar (M) groups, coronectomy was performed on the maxillary first molar, with flap elevation in the MF group and without flap elevation in the MNF group. The incisor groups were sacrificed on day 7, and the molar groups on days 7 and 14. Clinical healing, tooth movement, and histological and immunohistochemical analyses were performed. Results: InF and InNF groups showed tooth eruption similar to or the same as that before coronectomy, whereas the MF and MNF groups’ roots moved slowly. In InF and InNF groups, the pulp at the maturation zone was mineralized, but apical pulp vitality was maintained. MF and MNF groups showed bacterial infection and inflammation on day 7, with mineralization on day 14; however, apical pulp vitality was maintained. The MF group showed varied healing patterns, whereas the MNF group had consistent results across individuals. Conclusion Both incisors and molars are meaningful models for coronectomy. However, for consistent experimental results, coronectomy without flap elevation on the maxillary first molar is recommended.

Purpose: This study aimed to develop an animal model suitable for coronectomy research. Materials and Methods: Eighteen Sprague-Dawley rats were divided into six groups: incisor control (InC), incisor flap (InF), incisor non-flap (InNF), molar control (MC), molar flap (MF), and molar non-flap (MNF). Coronectomy was not performed in the control groups (InC and MC). In the incisor (In) groups, coronectomy was performed on the mandibular incisors, with flap elevation in the InF group and without flap elevation in the InNF group. In the molar (M) groups, coronectomy was performed on the maxillary first molar, with flap elevation in the MF group and without flap elevation in the MNF group. The incisor groups were sacrificed on day 7, and the molar groups on days 7 and 14. Clinical healing, tooth movement, and histological and immunohistochemical analyses were performed. Results: InF and InNF groups showed tooth eruption similar to or the same as that before coronectomy, whereas the MF and MNF groups’ roots moved slowly. In InF and InNF groups, the pulp at the maturation zone was mineralized, but apical pulp vitality was maintained. MF and MNF groups showed bacterial infection and inflammation on day 7, with mineralization on day 14; however, apical pulp vitality was maintained. The MF group showed varied healing patterns, whereas the MNF group had consistent results across individuals. Conclusion Both incisors and molars are meaningful models for coronectomy. However, for consistent experimental results, coronectomy without flap elevation on the maxillary first molar is recommended.

Purpose: This study aimed to develop an animal model suitable for coronectomy research. Materials and Methods: Eighteen Sprague-Dawley rats were divided into six groups: incisor control (InC), incisor flap (InF), incisor non-flap (InNF), molar control (MC), molar flap (MF), and molar non-flap (MNF). Coronectomy was not performed in the control groups (InC and MC). In the incisor (In) groups, coronectomy was performed on the mandibular incisors, with flap elevation in the InF group and without flap elevation in the InNF group. In the molar (M) groups, coronectomy was performed on the maxillary first molar, with flap elevation in the MF group and without flap elevation in the MNF group. The incisor groups were sacrificed on day 7, and the molar groups on days 7 and 14. Clinical healing, tooth movement, and histological and immunohistochemical analyses were performed. Results: InF and InNF groups showed tooth eruption similar to or the same as that before coronectomy, whereas the MF and MNF groups’ roots moved slowly. In InF and InNF groups, the pulp at the maturation zone was mineralized, but apical pulp vitality was maintained. MF and MNF groups showed bacterial infection and inflammation on day 7, with mineralization on day 14; however, apical pulp vitality was maintained. The MF group showed varied healing patterns, whereas the MNF group had consistent results across individuals. Conclusion Both incisors and molars are meaningful models for coronectomy. However, for consistent experimental results, coronectomy without flap elevation on the maxillary first molar is recommended.

Tumor hypoxia, a common feature occurring in nearly all human solid tumors is a major contributing factor for failures of anticancer therapies. Because ionizing radiation depends heavily on the presence of molecular oxygen to produce cytotoxic effect, the negative impact of tumor hypoxia had long been recognized. In this review, we will highlight some of the past attempts to overcome tumor hypoxia including hypoxic radiosensitizers and hypoxia-selective cytotoxin. Although they were (still are) a very clever idea, they lacked clinical efficacy largely because of ‘reoxygenation’ phenomenon occurring in the conventional low dose hyperfractionation radiotherapy prevented proper activation of these compounds. Recent meta-analysis and imaging studies do however indicate that there may be a significant clinical benefit in lowering the locoregional failures by using these compounds. Latest technological advancement in radiotherapy has allowed to deliver high doses of radiation conformally to the tumor volume. Although this technology has brought superb clinical responses for many types of cancer, recent modeling studies have predicted that tumor hypoxia is even more serious because ‘reoxygenation’ is low thereby leaving a large portion of hypoxic tumor cells behind. Wouldn’t it be then reasonable to combine hypoxic radiosensitizers and/or hypoxia-selective cytotoxin with the latest radiotherapy? We will provide some preclinical and clinical evidence to support this idea hoping to revamp an enthusiasm for hypoxic radiosensitizers or hypoxia-selective cytotoxins as an adjunct therapy for radiotherapy.
Anoxia* ; Cytotoxins ; Hope ; Humans ; Oxygen ; Radiation, Ionizing ; Radiotherapy* ; Treatment Outcome ; Tumor Burden

Recent advancement in the radiotherapy technology has allowed conformal delivery of high doses of ionizing radiation precisely to the tumors while sparing large volume of the normal tissues, which have led to better clinical responses. Despite this technological advancement many advanced tumors often recur and they do so within the previously irradiated regions. How could tumors recur after receiving such high ablative doses of radiation? In this review, we outlined how radiation can elicit anti-tumor responses by introducing some of the cytokines that can be induced by ionizing radiation. We then discuss how tumor hypoxia, a major limiting factor responsible for failure of radiotherapy, may also negatively impact the anti-tumor responses. In addition, we highlight how there may be other populations of immune cells including regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and tumor-associated macrophages (TAMs) that can be recruited to tumors interfering with the anti-tumor immunity. Finally, the impact of irradiation on tumor hypoxia and the immune responses according to different radiotherapy regimen is also delineated. It is indeed an exciting time to see that radiotherapy is being combined with immunotherapy in the clinic and we hope that this review can add an excitement to the field.
Anoxia ; Cytokines ; Hope ; Immune System ; Immunotherapy ; Macrophages ; Radiation, Ionizing ; Radiotherapy ; T-Lymphocytes, Regulatory

No abstract available.
Eructation* ; Speech Therapy*

Background: Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes. Results: In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals. Conclusions UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.

Background: Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes. Results: In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals. Conclusions UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.

Background: Uncoupling protein 1 (UCP1) is a proton uncoupler located across the mitochondrial membrane gener‑ ally involved in thermogenesis of brown adipose tissues. Although UCP1 is known to be strongly expressed in brown adipocytes, recent evidence suggest that white adipocytes can also express UCP1 under certain circumstances such as cold- or β-adrenergic receptor-stimulation, allowing them to acquire brown adipocyte-like features thereby becoming ’beige’ adipocytes. Results: In this study, we report that UCP1 can be expressed in adipose-tissue macrophages (ATM) lacking func‑ tional hypoxia-inducible factor-1 (HIF-1) and this does not require cold- nor β-adrenergic receptor activation. By using myeloid-specific Hif-1α knockout (KO) mice, we observed that these mice were protected from diet-induced obesity and exhibited an improved thermogenic tolerance upon cold challenge. ATM isolated from white adipose tissues (WAT) of these mice fed with high fat diet exhibited significantly higher M2-polarization, decreased gly‑ colysis, increased mitochondrial functions and acetyl-CoA levels, along with increased expression of Ucp1, peroxisome proliferator activated receptor-gamma co-activator-1a, and others involved in histone acetylation. Consistent with the increased Ucp1 gene expression, these ATM produced a significant amount of heat mediating lipolysis of cocultured adipocytes liberating free fatty acid. Treating ATM with acetate, a substrate for acetyl-CoA synthesis was able to boost the heat production in wild-type or Hif-1α-deficient but not UCP1-deficient macrophages, indicating that UCP1 was necessary for the heat production in macrophages. Lastly, we observed a significant inverse correlation between the number of UCP1-expressing ATM in WAT and the body mass index of human individuals. Conclusions UCP1-expressing ATM produce the heat to mediate lipolysis of adipocytes, indicating that this can be a novel strategy to treat and prevent diet-induced obesity.