Essential amino acid starvation induces cell cycle arrest, autophagy, and inhibits osteogenic differentiation in murine osteoblast.

This study investigates the effects of essential amino acid (EAA) starvation on murine osteoblasts cells and the underlying mechanisms. We performed and observed the cell proliferation, autophagy, and osteogenic differentiation under deprivation of EAA in vitro. The results showed that EAA starvation resulted in cell cycle arrest via phosphorylation of the MAPK signaling pathway, leading to inhibition of cell proliferation and osteogenic differentiation. Additionally, the LKB1-AMPK signaling pathway was also found to be phosphorylated, inducing autophagy. These findings highlight the significant role of EAA in regulating cellular processes. Furthermore, this study contributes to our understanding of the effects of nutrient deprivation on cellular physiology and may aid in the development of novel therapeutic strategies for diseases associated with amino acid metabolism.

Surface modification affects human gingival epithelial cell behavior on polyetheretherketone surfaces.

Gingival epithelial attachment to the abutment is important for the prevention of peri-implantitis. Polyetheretherketone (PEEK) has recently gained attention as an alternative material to titanium; however, it is biologically inert, which is disadvantageous for obtaining soft tissue sealing of the transmucosal part of the implant abutment. Therefore, ultraviolet (UV) irradiation, argon plasma irradiation, and buffing were selected as treatments to modify the PEEK surface. None of the treatments had any effect on the material's mechanical strength. The UV and plasma treatments did not significantly affect the surface morphology. Surface elemental analysis showed a decrease in carbon content and an increase in oxygen content and wettability for all treatments. Human gingival epithelial cell adhesion, proliferation, and the expression of adhesion proteins integrin ß4 and laminin 332, were increased. Surface modification to PEEK was suggested to enhance cell activity on PEEK.

An elderly woman with Birt-Hogg-Dubé syndrome having multiple pulmonary cysts mimicking lymphangioleiomyomatosis.

The characteristics of the pulmonary cysts on the high-resolution computed tomography (HRCT) chest images are an important diagnostic clue to distinguish among cystic lung diseases. The diagnostic accuracy of HRCT was reported to be as high as 90% by experienced pulmonologists and radiologists. Herein, we report the case of an elderly woman with Birt-Hogg-Dubé syndrome (BHDS) whose HRCT images displayed lymphangioleiomyomatosis-like features of the pulmonary cysts, rendering it difficult for us to diagnose BHDS. This case illustrates the significance of a thorough anamnesis, physical examination, and skin biopsy of facial papules to establish an accurate diganosis.

Effects of α-tocopherol on bone marrow mesenchymal cells derived from type II diabetes mellitus rats.

It is widely accepted that vitamin E (VE) acts as an antioxidant and is involved in various metabolic systems including the regulation of gene expression and inhibition of cell proliferation. The most predominant isoform of VE in the living body is α-tocopherol. However, the influence of α-tocopherol on bone marrow mesenchymal cells (BMMCs) in a background of type II diabetes mellitus (DM) has not been investigated. The focus of the present study was to clarify the effect of α-tocopherol on BMMCs derived from rats with type II DM and the underlying mechanisms involved. BMMCs were isolated from rats with type II DM. The BMMCs were either untreated or exposed to α-tocopherol at concentrations of 1.0, 10, and 100 µM, and the resulting effects of α-tocopherol on cell proliferation, H2O2 activity, and antioxidant and inflammatory cytokine production were examined. At 100 µM, α-tocopherol had no effect on cell proliferation, but H2O2 activity was significantly increased. At 10 µM, α-tocopherol increased the gene expression of IL-1ß, and markedly promoted that of TNF-α. Expression of catalase in the presence of 100 µM α-tocopherol was lower than for the other concentrations. At a low concentration, α-tocopherol exerted good antioxidant and anti-inflammatory effects on BMMCs. The study suggests that maintaining α-tocopherol at a low concentration might promote the recovery of BMMCs from oxidative stress.

High-dose methylprednisolone with chemotherapy for invasive thymoma: a case report.

A case of invasive thymoma that responded well to the administration of a high-dose methylpredonisolone with cisplatin and adriamycin is reported. A 63-year-old woman was admitted to our hospital because of dyspnea, chest oppression and edema of the face. Chest CT revealed a large mass in the anterior mediastinum with the opacification of superior vena cava. Biopsy specimens from the mass revealed a spindle cell thymoma, consisting of epithelial cells and lymphoid cells. A diagnosis of invasive thymoma was made and the patient was intravenously treated with a high-dose of methylprednisolone (1000 mg on days 1-5 and 500 mg on days 6 and 7), cisplatin (80 mg/m2 on day 1) and adriamycin (40 mg/m2 on day 1). The treatment with three courses of this combined chemotherapy resulted in the improvement and regression of all clinical signs and symptoms. This case demonstrated that a high-dose methylprednisolone with cisplatin and adriamycin might be potentially effective for invasive thymoma.

High Glucose Concentrations Suppress the Proliferation of Human Periodontal Ligament Stem Cells and Their Differentiation Into Osteoblasts.

BACKGROUND: Diabetes mellitus (DM) is a major risk factor for periodontal disease and affects various cellular functions. Periodontal ligament stem cells (PDLSCs) play an important role in periodontal tissue regeneration; however, the effect of hyperglycemia on PDLSCs is unclear. The aim of this study is to investigate whether hyperglycemia affects periodontal tissue regeneration, using human PDLSCs and high-glucose medium as a model of DM. METHODS: PDLSCs were obtained from healthy adult human mandibular third molars. Cell proliferation, osteoblastic differentiation, and proinflammatory cytokine expression were investigated by culturing PDLSCs in media supplemented with four different glucose concentrations representative of control patients (5.5 mM), patients with postprandial or controlled DM (8.0 mM), and patients with uncontrolled DM (12.0 and 24.0 mM). The molecular effects of hyperglycemia on PDLSC physiology were examined with a focus on the nuclear factor (NF)-(κB signaling pathway. The involvement of NF-κB was investigated with a specific NF-κB inhibitor in PDLSCs under hyperglycemic conditions. RESULTS: High glucose levels inhibited PDLSC proliferation and differentiation into osteoblasts but induced NF-κB activation and subsequent interleukin (IL)-6 and IL-8 expression. Treatment with an NF-κB inhibitor rescued the defects in cell proliferation and osteoblastic differentiation and inhibited the IL-6 expression caused by the high-glucose environment. CONCLUSION: The results of this study demonstrate that hyperglycemia inhibits human PDLSC proliferation and osteoblastic differentiation.

Successful treatment of hypertrophic osteoarthropathy by gefitinib in a case with lung adenocarcinoma.

Hypertrophic osteoarthropathy is an important manifestation of lung carcinoma, particularly in a non-small cell tumor, and hampers quality of life. Although removal of the primary tumor usually resolves this syndrome, effective treatment in patients with advanced lung carcinoma has not been established. Recently, an orally active, selective epidermal growth factor receptor tyrosine kinase (EGFR) inhibitor ("Gefitinib") provided clinical anti-tumor activity. We describe a 71-year-old male smoker with cough, who presented with clubbed fingers. A transbronchial lung biopsy (stage T2N3M1-IV) on a cavity lesion in the left lower lobe showed the features of adenocarcinoma, while bone scintigram revealed bilaterally symmetrical abnormal uptakes in the lower extremities, suggesting secondary hypertrophic osteoarthropathy. The serum level of growth hormone was increased to 1.42 ng/ml. Chemotherapy (cisplatin, vinorelbine) was not effective. Gefitinib, as a second-line therapy, induced disappearance of the abnormal accumulation on bone scintigraphy and decrease of the cavity in the lung and of serum growth hormone. The presented case suggests that the EGFR inhibitor might be a promising option for the treatment of hypertrophic osteoarthropathy with advanced lung adenocarcinoma.

Effect of Porphyromonas gingivalis lipopolysaccharide on bone marrow mesenchymal stem cell osteogenesis on a titanium nanosurface.

BACKGROUND: Titanium (Ti) dental implants have been widely used for prosthetic reconstruction of dentition. Unfortunately, peri-implantitis can result in failure of dental implant osseointegration. Lipopolysaccharide (LPS) acts as a chronic inflammatory stimulus and maintains peri-implant inflammation, worsening the prognosis for implant osseointegration. The purpose of this study is to determine the effects of 10 M NaOH-modified Ti surface with nanonetwork structure on the proliferation and osteogenic differentiation of rat bone marrow mesenchymal stem cells (BMMSCs) in the context of Porphyromonas gingivalis LPS exposure. METHODS: Titanium disks treated with 10 M NaOH solution and control were incubated with BMMSCs and exposed to P. gingivalis LPS (0, 0.1, or 1 µg/mL). The effects of the modified nanonetwork structure on osteogenic differentiation of rat BMMSCs were evaluated in the context of different concentrations of P. gingivalis LPS exposure. RESULTS: Rat BMMSCs on the 10 M NaOH-modified Ti surface with nanonetwork structure had higher levels of osteogenesis-related gene expression and significantly greater cell proliferation, alkaline phosphatase activity, and extracellular matrix deposition and mineralization than cells on the untreated Ti surfaces, in all the groups with different doses of P. gingivalis LPS exposure. CONCLUSION: The 10 M NaOH-modified Ti surface with nanonetwork structure has better endotoxin tolerance under P. gingivalis LPS exposure than the non-modified surface.

Tuberculous liver abscess not associated with lung involvement.

Hepatic tuberculosis is one of the uncommon forms of extrapulmonary tuberculosis. We report a 78-year-old woman who developed tuberculous liver abscesses with splenic abscess not associated with pulmonary foci. Ultrasonography and computed tomography of the abdomen showed the low-density lesions in the liver and spleen. Histopathology of specimens obtained by percutaneous needle biopsy revealed coagulation necrosis and epithelioid cells but not tumor cells, suggesting tuberculosis infection in the liver and spleen. Systemic chemotherapy with anti-tuberculous agents led to the improvement of the lesions in the liver as well as spleen. Although tuberculous liver abscess is a very rare case, it should be included in the differential diagnosis of unknown hepatic mass lesions.

[A case of Lemierre syndrome].

We present a case of Lemierre syndrome characterized by thrombophlebitis of the internal jugular vein with multiple metastatic foci after acute otopharyngeal infection in a 30-year-old woman. Despite treatment with tonsillectomy leading to a diagnosis of peritonsillar abscess, her condition worsened and she was admitted with high fever. Chest radiograph and CT scan of the thorax revealed multiple pulmonary cavities and pleural effusion on the right side. On neck CT, a thrombus was detected in the left internal jugular vein. She received with intravenous clindamycin (CLDM) and cefepime (CFPM) and progressively improved. Although Lemierre syndrome is a relatively uncommon disease with the potentially life-threatening complication of acute pharyngotonsillitis, this syndrome should be considered in cases of severe tonsillitis or pharyngitis.