Chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality throughout the world, is a highly complicated disease that includes chronic airway inflammation, airway remodeling, emphysema, and mucus hypersecretion.For respiratory function, an intact lung structure is required for efficient air flow through conducting airways and gas exchange in alveoli. Structural changes in small airways and inflammation are major features of COPD. At present, mechanisms involved in the genesis and development of COPD are poorly understood. Currently, there are no effective treatments for COPD. To develop better treatment strategies, it is necessary to study mechanisms of COPD using proper experimental models that can recapitulate distinctive features of human COPD. Therefore, this review will discuss representative established mouse models to investigate inflammatory processes and basic mechanisms of COPD. In addition, human COPD-mimicking human lung organoid models are introduced to help researchers overcome limits of mouse COPD models.

Chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality throughout the world, is a highly complicated disease that includes chronic airway inflammation, airway remodeling, emphysema, and mucus hypersecretion.For respiratory function, an intact lung structure is required for efficient air flow through conducting airways and gas exchange in alveoli. Structural changes in small airways and inflammation are major features of COPD. At present, mechanisms involved in the genesis and development of COPD are poorly understood. Currently, there are no effective treatments for COPD. To develop better treatment strategies, it is necessary to study mechanisms of COPD using proper experimental models that can recapitulate distinctive features of human COPD. Therefore, this review will discuss representative established mouse models to investigate inflammatory processes and basic mechanisms of COPD. In addition, human COPD-mimicking human lung organoid models are introduced to help researchers overcome limits of mouse COPD models.

Chronic obstructive pulmonary disease (COPD), a leading cause of morbidity and mortality throughout the world, is a highly complicated disease that includes chronic airway inflammation, airway remodeling, emphysema, and mucus hypersecretion.For respiratory function, an intact lung structure is required for efficient air flow through conducting airways and gas exchange in alveoli. Structural changes in small airways and inflammation are major features of COPD. At present, mechanisms involved in the genesis and development of COPD are poorly understood. Currently, there are no effective treatments for COPD. To develop better treatment strategies, it is necessary to study mechanisms of COPD using proper experimental models that can recapitulate distinctive features of human COPD. Therefore, this review will discuss representative established mouse models to investigate inflammatory processes and basic mechanisms of COPD. In addition, human COPD-mimicking human lung organoid models are introduced to help researchers overcome limits of mouse COPD models.

Background: General anesthesia is inevitable for pediatric patients undergoing surgery, though volatile anesthetic agents may cause neuroinflammation and neurodevelopmental impairment; however, the underlying pathophysiology remains unclear. We aimed to investigate the neuroinflammation mechanism in developing rat brains associated with sevoflurane exposure time, by identifying the specific damage-associated molecular patterns (DAMPs) pathway and evaluating the effects of non-steroidal anti-inflammatory drugs (NSAIDs) in alleviating neuroinflammation. Methods: A three-step experiment was conducted to investigate neuroinflammation induced by sevoflurane. First, the exposure time required for sevoflurane to cause neuroinflammation was determined. Next, the specific pathways of DAMPs involved in neuroinflammation by sevoflurane were identified. Finally, the effects of NSAIDs on sevoflurane-induced neuroinflammation were investigated. The expression of various molecules in the rat brain were assessed using immunohistochemistry, immunofluorescence, quantitative real-time polymerase chain reaction, western blot analysis, and enzyme-linked immunosorbent assay. Results: In total, 112 rats (aged 7 days) were used, of which six rats expired during the experiment (mortality rate, 5.3%). Expression of CD68, HMGB-1, galectin-3, TLR4, TLR9, and phosphorylated NF-κB was significantly increased upon 6 h of sevoflurane exposure. Conversely, transcriptional levels of TNF-α and IL-6 significantly increased and IFN-γ significantly decreased after 6 h of sevoflurane exposure. Co-administration of NSAIDs with sevoflurane anesthesia significantly attenuated TNF-α and IL-6 levels and restored IFN-γ levels. Conclusions In conclusion, 6 h of sevoflurane exposure induces neuroinflammation through the DAMPs pathway, HMGB-1, and galectin-3. Co-administration of ibuprofen reduced sevoflurane-induced neuroinflammation.

Cochlear implants (CIs) are recognized as a safe and effective treatment for auditory rehabilitation for people of all ages with severe to profound sensorineural hearing loss. As the indications for CIs have expanded, recent advances in technology have focused mostly on preserving residual hearing. Because trauma to the internal structure of the cochlea can affect residual hearing, development has been focused on minimally invasive surgical procedures using robot technology along with the growth of interest in the field of CI surgery over the recent years. Maintaining a slow, steady rate of electrode insertion is widely accepted as an important factor associated with reduced intraoperative inner ear trauma and improved postoperative hearing outcomes. The use of robots have resulted in maintaining a slow rate of electrode insertion and reduced the degree of innate hand tremor in the movement of electrode array. We hereby present our experience of a successful robotic CI using iotaSOFT (iotaMotion, Inc.) and also present a review of the literature.

A 35-year-old male presented with atypical aphasia following left anterior choroidal artery infarction associated with distal internal carotid artery dissection. He presented with 1) lexical-semantic deficit without semantic impairment, 2) frequent surface errors (both surface dyslexia and dysgraphia), and 3) intact non-word reading/repetition (preserved sub-lexical route), suggesting deficit in the phonological output lexicon. Diffusion-tensor tractography analysis revealed disruption in the inferior fronto-occipital fasciculus and inferior longitudinal fasciculus, which might serve as potential subcortical neural correlates for phonological output lexicon.

Autophagy is a process of eliminating damaged or unnecessary proteins and organelles, thereby maintaining intracellular homeostasis. Deregulation of autophagy is associated with several diseases including cancer. Contradictory dual roles of autophagy have been well established in cancer. Cytoprotective mechanism of autophagy has been extensively investigated for overcoming resistance to cancer therapies including radiotherapy, targeted therapy, immunotherapy, and chemotherapy. Selective autophagy inhibitors that directly target autophagic process have been developed for cancer treatment. Efficacies of autophagy inhibitors have been tested in various pre-clinical cancer animal models. Combination therapies of autophagy inhibitors with chemotherapeutics are being evaluated in clinal trials. In this review, we will focus on genetical and pharmacological perturbations of autophagy-related proteins in different steps of autophagic process and their therapeutic benefits. We will also summarize combination therapies of autophagy inhibitors with chemotherapies and their outcomes in pre-clinical and clinical studies. Understanding of current knowledge of development, progress, and application of cytoprotective autophagy inhibitors in combination therapies will open new possibilities for overcoming drug resistance and improving clinical outcomes.

Tumor-to-tumor metastasis (TTM) is defined as the hematogenous metastasis within a primary host tumor from a donor neoplasm. Since there is insufficient evidence regarding the pathophysiology, clinical course, and management of TTM, there are no precise guidelines for its management. A 73-yearold female patient diagnosed with breast cancer was found to have convexity meningioma. Since the size of tumor and peritumoral brain edema increased during follow-up period, the meningioma was treated with surgical resection. Postoperatively, histopathologic examination confirmed metastasis of invasive ductal carcinoma within a secretory meningioma. The final diagnosis was TTM of breast cancer in meningioma. Here, we report a rare case of intra-meningioma metastasis and a review of literature to provide a better understanding of this rare phenomenon.

Mebendazole (MBZ), a microtubule depolymerizing drug commonly used for the treatment of helminthic infections, has been suggested as a repositioning candidate for the treatment of brain tumors. However, the efficacy of MBZ needs further study to improve the beneficial effect on the survival of those patients. In this study, we explored a novel strategy to improve MBZ efficacy using a drug combination. When glioblastoma cells were treated with MBZ, cell proliferation was dose-dependently inhibited with an IC50of less than 1 µM. MBZ treatment also inhibited glioblastoma cell migration with an IC50 of less than 3 µM in the Boyden chamber migration assay. MBZ induced G2-M cell cycle arrest in U87 and U373 cells within 24 h. Then, at 72 h of treatment, it mainly caused cell death in U87 cells with an increased sub-G1 fraction, whereas polyploidy was seen in U373 cells. However, MBZ treatment did not affect ERK1/2 activation stimulated by growth factors. The marked induction of autophagy by MBZ was observed, without any increased expression of autophagy-related genes ATG5/7 and Beclin 1. Co-treatment with MBZ and the autophagy inhibitor chloroquine (CQ) markedly enhanced the anti-proliferative effects of MBZ in the cells. Triple combination treatment with temozolomide (TMZ) (another autophagy inducer) further enhanced the anti-proliferative effect of MBZ and CQ. The combination of MBZ and CQ also showed an enhanced effect in TMZ-resistant glioblastoma cells. Therefore, we suggest that the modulation of protective autophagy could be an efficient strategy for enhancing the anti-tumor efficacy of MBZ in glioblastoma cells.