Combined Treatment of Mori folium and Mori Cortex Radicis Ameliorate Obesity in Mice via UCP-1 in Brown Adipocytes.

Mori Folium (Morus alba leaf, MF) and Mori Cortex Radicis (Morus alba root cortex, MR) have been studied for their anti-obesity effects by enhancing the browning process and inhibiting adipogenesis. However, important aspects of their protective mechanisms have not been thoroughly investigated, which could aid in developing functional food. Thus, this study aims to determine the synergistic effects of MF and MR against obesity and its associated mechanisms. In an in vitro cell culture model of brown adipocytes, a 1:1 mixture of MF and MR showed a synergistic effect on the expression of brown adipocyte-specific genes, including Ucp-1, Ppargc1a, Cbp/p300-interacting transactivator (Cited), Prdm16, Tbx1, and Fgf21 compared with either MF- or MR-treated conditions. Moreover, they demonstrated the involvement of cAMP and Ca2+ in induction of brown adipocyte-specific genes. In an in vivo model using HFD-fed mice, MF/MR significantly inhibited weight gain, plasma cholesterol, LDL, TG content, fat mass, and adipocyte size. Furthermore, MF/MR inhibited morphological alteration and the expressions of fatty acid synthesis genes such as Srebp1 and Fasn in the white adipose tissue. Thermogenesis genes were recovered in the brown adipose tissue with MF/MR supplementation, indicating that MF/MR regulated adipocytic dysmetabolism where AMPK signaling is involved. In conclusion, these results suggested that MF/MR regulates brown and beige adipocyte processes, providing one of the preventive functional food/herbal medicines against obesity and its associated metabolic diseases.

Case report: Bilateral posterior ischemic optic neuropathy in a patient with atrial fibrillation and multifocal embolic stroke.

An 80-year-old female with a history of diabetes mellitus (DM) and hypertension presented with sudden onset of sequential bilateral visual loss. The best visual acuity was light perception in the right eye and finger counting in the left eye, however, bilateral fundus did not reveal optic disc edema. Diffusion-weighted magnetic resonance imaging (MRI) of the brain revealed acute embolic stroke and diffusion restriction in the posterior portion of both optic nerves. The 24-h Holter monitor showed persistent atrial fibrillation (AF) with rapid ventricular response. The presence of painless and severe visual loss at onset unaccompanied by optic disc edema in the patient with newly detected uncontrolled AF and multiple embolic infarctions favored a diagnosis of non-arteritic posterior ischemic optic neuropathy (PION). The current case contributes to better understanding of PION pathophysiology and associated risk factors, indicating a possible relationship between non-arteritic PION and uncontrolled AF and embolic cerebral infarction.

Endoscopic finding of leiomyosarcoma in a neurofibromatosis patient.

A man with a history of neurofibromatosis presented to our hospital with a soft palate mass. Since the patient had neurofibromatosis, we diagnosed the mass as a neurofibroma and planned annual regular follow-up without any treatment. Five months later, the patient visited our emergency department because of uncontrolled epistaxis, and the mass was enlarged to the extent of the airway obstruction. Endoscopic resection was performed and the tumor was confirmed to be a leiomyosarcoma. The malignant potential of the new lesion in a neurofibromatosis patient should be actively evaluated and treated, if required.

Deacetylation of XBP1s by sirtuin 6 confers resistance to ER stress-induced hepatic steatosis.

The active spliced form of X-box-binding protein 1 (XBP1s) is a key modulator of ER stress, but the functional role of its post-translational modification remains unclear. Here, we demonstrate that XBP1s is a deacetylation target of Sirt6 and that its deacetylation protects against ER stress-induced hepatic steatosis. Specifically, the abundance of acetylated XBP1s and concordant hepatic steatosis were increased in hepatocyte-specific Sirt6 knockout and obese mice but were decreased by genetic overexpression and pharmacological activation of Sirt6. Mechanistically, we identified that Sirt6 deacetylated a transactivation domain of XBP1s at Lys257 and Lys297 and promoted XBP1s protein degradation through the ubiquitin-proteasome system. Overexpression of XBP1s, but not its deacetylation mutant 2KR (K257/297R), in mice increased lipid accumulation in the liver. Importantly, in liver tissues obtained from patients with nonalcoholic fatty liver disease (NAFLD), the extent of XBP1s acetylation correlated positively with the NAFLD activity score but negatively with the Sirt6 level. Collectively, we present direct evidence supporting the importance of XBP1 acetylation in ER stress-induced hepatic steatosis.

Benign metastasizing leiomyoma presenting as multiple cystic pulmonary nodules: a case report.

BACKGROUND: Benign metastatic leiomyoma (BML) is an extremely rare disease. Although uterine leiomyomas are benign histologically, they can metastasize to distant sites. While the incidence is very low, the lung is the organ most frequently affected by BML. Pulmonary BML usually presents as numerous well-defined nodules of various sizes, while the cavitary or cystic features in the nodules are rarely observed on radiologic images. CASE PRESENTATION: A 52-year-old woman complained of cough and dyspnea for one month. She had been previously diagnosed with uterine leiomyoma and had undergone total hysterectomy about 14 years prior. High-resolution computed tomography (CT) images showed that there were multiple cystic nodules of various sizes in both lungs. Pathologic examination revealed that the pulmonary nodule had complex branching glandular structures lined by a single layer of simple cuboidal to columnar epithelium that was surrounded by abundant spindle cells. Additional immunohistochemistry data suggested that pulmonary nodule diagnosis was BML-associated uterine leiomyoma. CONCLUSION: In this report, we introduce an interesting case of pulmonary BML that presented as a combination of various kinds of nodules including simple round nodules, simple cysts, and cysts with a solid portion, which are very rare radiologic features of BML in lung. In addition, when the patient is a woman of reproductive age, physicians should meticulously review the gynecological history and suspect BML when there are various cystic pulmonary lesions.

Repeated occurrence of second primary lung cancer at different sites in trachea: a case report.

Multiple or second primary lung cancers can develop at any sites in the lung with same or different histologic types, synchronously and/or metachronously. In case of metachronous occurrence of the second primary lung cancer, it is easy to confuse with the primary lung cancer as a recurrence of precedent lung malignancy treated successfully or metastasis. Previous reports have demonstrated that majority of the second primary lung malignancies have same histologic types regardless of their developing time and location. However, the repeated occurrence of the second primary lung malignancy, in particular with the different histologic features, is a very rare condition.A 62-year-old male who had past history of squamous cell carcinoma treated with surgery and adjuvant chemotherapy and the recurrence of lung malignancy on the trachea, which was also resected successfully visited our hospital due to blood tinged sputum. Evaluation using bronchoscopy and chest computed tomography revealed the tracheal mass looked similar grossly to the previous recurred tracheal mass that was resected surgically. Unexpectedly, the newly developed tracheal mass was confirmed as small cell lung cancer, the different histologic type from previous ones.In this report, we describe an interesting case of subsequent occurrence of second primary lung cancers showing histologic shifting at different sites in trachea, suggesting that it is important for physician to make an effort to identify the histologic characteristics of second primary lung cancers for the correct and adequate treatment no matter what they exhibit similar gross morphology.

Multiple pulmonary metastases from giant cell tumor of a hand.

Giant cell tumor (GCT) of bone has been described as the most challenging benign bone tumors. The majority of these tumors, classically, are involved in the epiphysis of long bones; however, on rare occasions, the tumors occur in the small bones of hands and feet. Although this disorder is benign, GCTs show a tendency of significant bone destruction, local recurrence and, occasionally, pulmonary metastasis. Approximately 3% of GCTs is known to metastasize to the lung. Herein, the authors describe an extremely rare case of multiple pulmonary metastatic GCTs in a 54-year-old man who presented asymptomatic pulmonary nodular lesions detected incidentally on chest x-ray of routine health checkup. He underwent chemotherapy with adriamycin and cisplatin and achieved nearly complete remission.

Effectiveness of rosiglitazone on bleomycin-induced lung fibrosis: Assessed by micro-computed tomography and pathologic scores.

Peroxisome proliferator-activated receptor-γ (PPARγ) agonists exhibit potent anti-fibrotic effects in the lung and other tissues. Recently, micro-computed tomography (CT) has been a useful tool for the investigation of lung diseases in small animals and is now increasingly applied to visualize and quantify the pulmonary structures. However, there is little information on the assessment for therapeutic effects of PPARγ agonists on the pulmonary fibrosis in mice using micro-CT. This study was aimed to determine the capability of micro-CT in examining the effects of rosiglitazone on pulmonary fibrosis. We used a murine model of bleomycin-induced lung fibrosis to evaluate the feasibility of micro-CT in evaluating the therapeutic potential of rosiglitazone on pulmonary fibrosis, comparing with pathologic scores. On micro-CT findings, ground glass opacity (80%) and consolidation (20%) were observed predominantly at 3 weeks after the instillation of bleomycin, and the radiologic features became more complex at 6 weeks. In bleomycin-instilled mice treated with rosiglitazone, the majority (80%) showed normal lung features on micro-CT. Radiological-pathologic correlation analyses revealed that ground glass opacity and consolidation were correlated closely with acute inflammation, while reticular opacity was well correlated with histological honeycomb appearance. These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis in mice and that the visualization of bleomycin-induced pulmonary fibrosis using micro-CT is satisfactory to assess the effects of rosiglitazone. It implies that micro-CT can be applied to evaluate therapeutic efficacies of a variety of candidate drugs for lung diseases.

Lysyl oxidase-like-1 enhances lung metastasis when lactate accumulation and monocarboxylate transporter expression are involved.

The role that lysyl oxidase-like­1 (LOXL-1) may play in cancer metastasis due to its specific collagen accumulation characteristics has not been investigated extensively. This study was performed to examine the role of LOXL-1 in cancer metastasis. In vitro and in vivo cancer metastasis experiments were performed with B16F10 cells. Using the immunoblotting technique, the expression of LOXL-1, monocarboxylate transporter (MCT)1/2 and matrix metalloproteinase (MMP)2/9 was examined in a cell culture model and in primary and metastatic site samples from non­small cell lung carcinoma patients. Immunohistochemistry was also performed. According to immunohistochemical analysis of the non-small cell lung carcinoma patient samples, LOXL-1, MCT1/2 and MMP2/9 were expressed more highly in metastatic sites compared to primary sites. In in vivo studies, LOXL-1-overexpressing B16F10 cells yielded higher numbers of cancer nodules following their injection into mouse tail veins. Transfection of LOXL-1 siRNA into the cells prior to injection blocked lung metastasis. In vitro, the overexpression of LOXL-1 increased cell mobility and invasiveness, with increased extracellular accumulation of lactate at a low pH. The lactate transporter, MCT1/2, was highly expressed in LOXL­1-overexpressing cells. LOXL-1 knockdown through siRNA inhibited cell motility and invasiveness, showing relatively lower lactate accumulation and expression of MCT1/2 than under control conditions. This study elucidates extracellular pH-associated matrix degradation as a potential mechanism for LOXL-1-induced cancer metastasis.