Phenylbutyrate Ameliorates High-Fat Diet-Induced Obesity via Brown Adipose Tissue Activation.

Obesity, which is characterized by an excessive accumulation of body fat, is one of the critical factors causing metabolic syndrome. Many studies have been performed to identify appropriate agents to control obesity, but toxicity remains a problem. Herein, we identified that phenylbutyrate (PBA), which has been used to treat urea cycle disorder with very low toxicity for a long time, efficiently inhibited high fat-induced body weight gain in a diet-induced obesity mouse model (DIO model). PBA treatment decreased body fat mass and increased lean composition. Moreover, PBA increased brown adipose tissue (BAT) activity by increasing glucose uptake, thereby improving glucose tolerance and insulin tolerance. Interestingly, PBA could induce the expression of liver type phosphofructokinase (PFKL), a key enzyme in the glycolytic pathway, and knocking down PFKL dramatically repressed the expression level of Ucp1 as well as those of Prdm16, Cidea, Pgc1α, and Pparγ, which are marker genes for BAT activation. These results strongly suggested that PBA could increase energy expenditure by increasing BAT activity via the induction of PFKL. Taken together, PBA could be used as a therapeutic agent for people with obesity to prevent the development of metabolic syndrome.

Pyruvate Dehydrogenase Kinase Is a Metabolic Checkpoint for Polarization of Macrophages to the M1 Phenotype.

Metabolic reprogramming during macrophage polarization supports the effector functions of these cells in health and disease. Here, we demonstrate that pyruvate dehydrogenase kinase (PDK), which inhibits the pyruvate dehydrogenase-mediated conversion of cytosolic pyruvate to mitochondrial acetyl-CoA, functions as a metabolic checkpoint in M1 macrophages. Polarization was not prevented by PDK2 or PDK4 deletion but was fully prevented by the combined deletion of PDK2 and PDK4; this lack of polarization was correlated with improved mitochondrial respiration and rewiring of metabolic breaks that are characterized by increased glycolytic intermediates and reduced metabolites in the TCA cycle. Genetic deletion or pharmacological inhibition of PDK2/4 prevents polarization of macrophages to the M1 phenotype in response to inflammatory stimuli (lipopolysaccharide plus IFN-γ). Transplantation of PDK2/4-deficient bone marrow into irradiated wild-type mice to produce mice with PDK2/4-deficient myeloid cells prevented M1 polarization, reduced obesity-associated insulin resistance, and ameliorated adipose tissue inflammation. A novel, pharmacological PDK inhibitor, KPLH1130, improved high-fat diet-induced insulin resistance; this was correlated with a reduction in the levels of pro-inflammatory markers and improved mitochondrial function. These studies identify PDK2/4 as a metabolic checkpoint for M1 phenotype polarization of macrophages, which could potentially be exploited as a novel therapeutic target for obesity-associated metabolic disorders and other inflammatory conditions.

Chronic maxillary sinusitis and diabetes related maxillary osteonecrosis: a case report.

Dental infections and maxillary sinusitis are the main causes of osteomyelitis. Osteomyelitis can occur in all age groups, and is more frequently found in the lower jaw than in the upper jaw. Systemic conditions that can alter the patient's resistance to infection including diabetes mellitus, anemia, and autoimmune disorders are predisposing factors for osteomyelitis. We report a case of uncommon broad maxillary osteonecrosis precipitated by uncontrolled type 2 diabetes mellitus and chronic maxillary sinusitis in a female patient in her seventies with no history of bisphosphonate or radiation treatment.

Bisphosphonate-related osteonecrosis of the jaw in a patient with osteoporosis following treatment of testicular cancer: a case report.

Bisphosphonate-related osteonecrosis of the jaw (BRONJ) occurs mainly in female patients. In males the occurrence rate is low, which seems to be related to the low incidence of osteoporosis in men. Unfortunately, BRONJ tends to be ignored in general dental clinics in male patients with a history of osteoporosis treatment. BRONJ occurred in a male patient due to the clinician's lack of interest in the patient's history. In this case, the male patient was on bisphosphonate therapy because of a orchiectomy, and a dental treatment was performed without consideration of his medical history, resulting in BRONJ. We performed careful examinations and treatment with antibiotics and surgical operations. The postoperative healing was successful. In light of this particular case, we concluded that careful listening to the patient's history is very important.

Retrospective clinical study of mandible fractures.

OBJECTIVES: The purpose of this article is to analyze the incidence, demographic distribution, type, and etiology of mandible fractures that were treated by the Department of Oral and Maxillofacial Surgery in Kyung Hee University Dental Hospital from January 2002 to December 2012. MATERIALS AND METHODS: This was a descriptive and analytic retrospective study that evaluated 735 patients that were treated for mandible fracture. RESULTS: This study included 1,172 fractures in 735 patients. The ratio of male to female patients was 5.45 : 1; the maximum value was in patients between 20 and 29 years (38.1%) and the minimum in patients over 70 years old. The monthly distribution of facial fractures peaked in the fall and was lower during winter. No specific correlation was identified based on the annual fracture distribution. Among the 735 fracture patients, 1.59 fracture lines were observed per patient. The most frequent site was the symphysis, which accounted for a total of 431 fractures, followed by the angle (348), condyle (279), and body (95). The symphysis with angle was the most common site identified in combination with fracture and accounted for 22.4%, followed by symphysis with condyle (19.8%). The angle was the most frequent site of single fractures (20.8%). The major cause of injury was accidental trauma (43.4%), which was followed by other causes such as violence (33.9%), sports-related accidents (10.5%), and traffic accidents (10.1%). Fracture incidents correlated with alcohol consumption were reported between 10.0%-26.9% annually. CONCLUSION: Although mandible fracture pattern is similar to the previous researches, there is some changes in the etiologic factors.

Eagle's syndrome: a case report.

Eagle's syndrome is a disease caused by an elongated styloid process or calcified stylohyoid ligament. Eagle defined the disorder in 1937 by describing clinical findings related to an elongated styloid process, which is one of the numerous causes of pain in the craniofacial and cervical region. The prevalence of individuals with this anatomic abnormality in the adult population is estimated to be 4% with 0.16% of these individuals reported to be symptomatic. Eagle's syndrome is usually characterized by neck, throat, or ear pain; pharyngeal foreign body sensation; dysphagia; pain upon head movement; and headache. The diagnosis of Eagle's syndrome must be made in association with data from the clinical history, physical examination, and imaging studies. Patients with increased symptom severity require surgical excision of the styloid process, which can be performed through an intraoral or an extraoral approach. Here, we report a rare case of stylohyoid ligament bilaterally elongated to more than 60 mm in a 51-year-old female. We did a surgery by extraoral approach and patient's symptom was improved.

Overexpression of serine-threonine receptor kinase-associated protein in colorectal cancers.

Transforming growth factor-beta (TGF-beta) regulates many cellular processes, including cellular proliferation and differentiation. Disruption of the TGF-beta signaling pathway can lead to cancer. Serine-threonine receptor kinase-associated protein (STRAP), an inhibitor of TGF-beta signaling, is an important regulator of cell proliferation. Here, in order to investigate the roles of STRAP in colorectal carcinogenesis, the expression of the STRAP protein was investigated in 59 colonic adenomas and 123 colorectal cancers by immunohistochemistry. Upregulation of STRAP protein was observed in 30 (50.8%) of 59 adenomas and 87 (70.7%) of 123 cancers, respectively. Statistically, overexpression of STRAP protein was not associated with clinicopathological parameters and 5 year survival (P > 0.05). Interestingly, significant association was observed between STRAP and Ki-67 positivity (P < 0.05), suggesting that STRAP contributes to an increased proliferate potential of tumor cells. These results indicate that upregulation of STRAP might play a role in tumor development as an early event for colorectal cancers.

Genetic alterations of the KLF6 gene in colorectal cancers.

To investigate whether the KLF6 gene plays an important role in the development and/or progression of colorectal cancers, we searched for mutations and allelic loss of the KLF6 gene in 123 colorectal adenocarcinomas by performing PCR-SSCP sequencing. We found five somatic missense mutations: S155N, G163S, G163D, P183L and G195S. Three of them affected the activation domain of KLF6 and four mutations were predicted to disrupt the putative phosphorylation sites. On LOH analysis, 63 cases were heterozygous for at least one marker and 27 cases (42.9%) showed allelic loss at these markers. These data further support that the KLF6 gene may be one of the candidate tumor suppressor genes in colorectal cancers and that genetic alteration of the KLF6 gene might play a role in the development of colorectal carcinomas.

Aberrant expression of krUppel-like factor 6 protein in colorectal cancers.

AIM: To investigate whether krUppel-like factor 6 (KLF6) plays an important role in the development and/or progression of colorectal cancer. METHODS: A total of 123 formalin-fixed and paraffin-embedded colorectal cancer specimens were analyzed by immunohistochemistry using tissue microarray for the expression of KLF6 protein. The specimens were collected over a 3-year period in the laboratories at our large teaching hospital in Seoul, Republic of Korea. The correlation of KLF6 expression with clinicopathologic parameters was analyzed by chi2 test and Bartholomew test. RESULTS: Normal colonic epithelium showed weak to moderate expression of KLF6, whereas reduced KLF 6 expression or loss of KLF6 expression was seen in 45 (36.6%) of the 123 colorectal carcinoma specimens. Interestingly, aberrant expression of KLF6 was detected in 25 (43.1%) of 58 cases with metastasis to regional lymph node and in 31 (47.0%) of 66 tumors more than 5 cm in size. Statistically, loss of KLF6 expression was significantly associated with tumor size (P < 0.05). However, there was no significant correlation between KLF6 expression and Dukes'stage (Bartholomew test, P > 0.05), tumor location and lymph node metastasis (chi2 test, P > 0.05). CONCLUSION: Loss of KLF6 expression may be a common and early event in colorectal carcinogenesis.

Altered expression of CDX2 in colorectal cancers.

CDX2 is a caudal-related homeobox transcription factor whose expression in the adult is normally restricted to the intestinal epithelium; it is implicated in the development and maintenance of the intestinal mucosa. The specific aim of this study was to elucidate the potential etiological role of CDX2 protein in colorectal carcinogenesis. We have analyzed the expression pattern of CDX2 protein in relation to the phenotype of 123 sporadic colorectal cancers by immunohistochemistry using tissue microarray. Strong CDX2 immunostaining was seen in the nuclei of corresponding normal intestinal epithelium. Interestingly, loss of CDX2 immunostaining was observed in 29 (23.6%) of 123 colorectal adenocarcinomas and its expression was correlated with the differentiation grade of the carcinoma (Chi-Square test, p<0.01). Clinically, CDX2 protein was immunopositive in 11 (91.7%) of 12 cases corresponding to stage A, 40 (85.1%) of 47 corresponding to stage B, 39 (69.6%) of 56 corresponding to stage C, and 4 (50.0%) of 8 corresponding to stage D. Statistically, CDX2 protein expression was related to tumor stage (Bartholomew test, p<0.05) and lymph node metastasis (Chi-Square test, p<0.05). These results indicate that loss of expression of CDX2 protein may play an important role in the tumorigenesis of colorectal cancers and that CDX2 expression represents a highly significant marker, which is able to identify a subset of patients at high risk.