Although studies on malrotation of the humerus possibly leading to dysfunction of the shoulder have been reported, studies on its causes are inadequate. The authors encountered a patient complaining of malrotation accompanied by dysfunction of the shoulder which occurred during treatment of a distal humeral fracture. The patient recovered the shoulder function by only correcting malrotation of the humerus without direct treatment on the shoulder, and we report it herein with a review of the literature.
Humans ; Humeral Fractures ; Humerus* ; Shoulder*

Mice deficient in the toll-like receptor (TLR) or the myeloid differentiation factor 88 (MyD88) are resistant to acute liver failure (ALF) with sudden death of hepatocytes. Chalcone derivatives from medicinal plants protect from hepatic damages including ALF, but their mechanisms remain to be clarified. Here, we focused on molecular basis of piperidylmethyloxychalcone (PMOC) in the treatment of TLR/MyD88-associated ALF. C57BL/6J mice were sensitized with D-galactosamine (GalN) and challenged with Escherichia coli lipopolysaccharide (LPS, TLR4 agonist) or oligodeoxynucleotide containing unmethylated CpG motif (CpG ODN, TLR9 agonist) for induction of ALF. Post treatment with PMOC sequentially ameliorated hepatic inflammation, apoptosis of hepatocytes, severe liver injury and shock-mediated death in ALF-induced mice. As a mechanism, PMOC inhibited the catalytic activity of TGF-β-activated kinase 1 (TAK1) in a competitive manner with respect to ATP, displaced fluorescent ATP probe from the complex with TAK1, and docked at the ATP-binding active site on the crystal structure of TAK1. Moreover, PMOC inhibited TAK1 auto-phosphorylation, which is an axis in the activating pathways of nuclear factor-κB (NF-κB) or activating protein 1 (AP1), in the liver with ALF in vivo or in primary liver cells stimulated with TLR agonists in vitro. PMOC consequently suppressed TAK1-inducible NF-κB or AP1 activity in the inflammatory injury, an early pathogenesis leading to ALF. The results suggested that PMOC could contribute to the treatment of TLR/MyD88-associated ALF with the ATP-binding site of TAK1 as a potential therapeutic target.
Adenosine Triphosphate ; Animals ; Apoptosis ; Catalytic Domain ; Chalcone ; Death, Sudden ; Escherichia coli ; Hepatocytes ; In Vitro Techniques ; Inflammation ; Liver ; Liver Failure, Acute* ; Mice ; Myeloid Differentiation Factor 88 ; Phosphotransferases ; Plants, Medicinal ; Toll-Like Receptors

Ionizing radiation produces reactive oxygen species, which exert diverse biological effects on cells and animals. We investigated alterations of heme oxygenase (HO) and non-protein thiols (NPSH), which are known as two major anti-oxidant enzymes, in female and male C57BL/6 mice in the lung, liver, and brain after whole-body gamma-irradiation with 10 Gy (1-7 days) as well as in the lung after whole-thorax gamma-irradiation (WTI) with 12.5 Gy (1-26 weeks). Most significant alteration of HO activity was observed in the liver, which elevated 250% in males. NPSH level in female liver was increased on the 5th-7th days but decreased in males on the 3rd day. In the lung, the elevation of HO activity in both sexes and the pattern of NPSH change were similar to that of the liver. On the other hand, the increase of HO activity on the 16th week and the decrease of NPSH level on the 2nd week were observed only in male lung after WTI. This study shows that the liver is the most sensitive tissue to gamma-irradiation-induced alterations of HO activity in both female and male mice. In addition, there exists significant differential effect of gamma-irradiation on anti-oxidant system in female and male mice.
Animals ; Brain/*enzymology/metabolism/radiation effects ; Comparative Study ; Female ; Gamma Rays ; Gene Expression Regulation, Enzymologic/radiation effects ; Liver/*enzymology/metabolism/radiation effects ; Lung/*enzymology/metabolism/radiation effects ; Male ; Mice ; Mice, Inbred C57BL ; RNA, Messenger/genetics/metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sex Factors ; Sulfhydryl Compounds/metabolism ; Time Factors ; Whole-Body Irradiation

beta-Glucans are naturally occurring polysaccharides that are produced by bacteria, yeast, fungi, and many plants. Although their pharmacological activities, such as immunomodulatory, anti-infective and anti-cancer effects, have been well studied, it is still unclear how beta-glucans exert their activities. However, recent studies on the beta-glucan receptors shed some light on their mechanism of action. Since beta-glucans have large molecular weights, they must bind surface receptors to activate immune cells. In this review, we summarize the immunopharmacological activities and the potential receptors of beta-glucans in immune cells.
Bacteria ; beta-Glucans ; Fungi ; Light ; Molecular Weight ; Polysaccharides ; Receptors, Immunologic ; Yeasts

Objectives: The coronavirus disease (COVID-19) pandemic has had various effects on mankind, especially children and adolescents.Because children and adolescents spend a lot of time at school, COVID-19 has had a great impact on school mental health. In this study, we investigated the effect of prolonged COVID-19 on school mental health. Methods: We prepared self-report questionnaires for depression (Children’s Depression Inventory, CDI), anxiety (Korean version of the Penn State Worry Questionnaire for Children; Generalized Anxiety Disorder-7, GAD-7), and post-traumatic stress (Primary Care Post-traumatic Stress Disorder, PC-PTSD) for administering to students aged between 7 and 18 years, recruited by a COVID-19 psychological prevention support group in the Gwangmyeong Mental Health Welfare Center for 2 years, in 2020 and 2021. Results: For children aged 7–12 years, there was no significant difference between the years 2020 and 2021 in the assessment of depression, anxiety, and post-traumatic stress. Conversely, for adolescents aged 13–18 years, there was a significant increase in the scale scores (CDI, PC-PTSD, and GAD-7). Conclusion Prolonged COVID-19 might have had a significant impact on the mental health of adolescents who spent a lot of time at school. When comparing the years 2020 and 2021, middle and high school students were more affected by COVID-19 than elementary school students.

The current understanding of the pathophysiology of mild traumatic brain injury (mTBI) is, without doubt, incomplete. Nevertheless, we tried to summarize the state-of-the-art explanation of how the brain is continuously injured even after a single impact. We also reviewed the real struggle of diagnosing mTBI, which culminated in showing the potential of blood-based biomarkers as an alternative or complementary way to overcome this difficulty. Pathophysiology of mTBI is subdivided into primary and secondary injuries. Primary injury is caused by a direct impact on the head and brain. Secondary injury refers to the changes in energy metabolism and protein synthesis/degradation resulting from the biochemical cascades as follows; calcium influx, mitochondrial dysfunction, fractured microtubules, and Wallerian degeneration, neuroinflammation, and toxic proteinopathy. Since the diagnosis of mTBI is made through the initial clinical information, it is difficult and inaccurate to diagnose mTBI without the absence of a witness or sign of head trauma. Blood-based biomarkers are expected to play an important role in diagnosing mTBI and predicting functional outcomes, due to their feasibility and the recent progress of targeted proteomics techniques (i.e., liquid chromatography tandem mass spectrometry [LC-MS/MS]).
Biomarkers* ; Brain ; Brain Concussion ; Brain Injuries* ; Calcium ; Chromatography, Liquid ; Craniocerebral Trauma ; Diagnosis ; Energy Metabolism ; Head ; Microtubules ; Proteomics ; Tandem Mass Spectrometry ; Wallerian Degeneration

Ceramide generated from sphingomyelin in response to ionizing radiation has been implicated as a second messenger to induce cellular proapoptotic signals. Both ceramide and its metabolic inhibitor, N, N-dimethyl-D-erythro-sphingosine (DMS), might lead to sustained ceramide accumulation in cells more efficiently, thereby sensitizing them to gamma-radiation-induced cell death. To delineate this problem, the clonogenic survival of Lewis lung carcinoma (LLC) cells was evaluated following exposure to radiation together with or without C2-ceramide, DMS, or both. The treatment of ceramide/DMS synergistically decreased the survival of the irradiated cells compared with treatment with ceramide or DMS alone. Ceramide/DMS-treated cells displayed several apoptotic features after gamma-irradiation, including increased sub G1 population, TUNEL-positive fraction, and poly-(ADP-ribose) polymerase (PARP) cleavage. We also observed ceramide/ DMS induced disruption of mitochondrial membrane potential (MMP) and activation of caspase- 9 and -3 in a radiation-dose-dependent manner. Furthermore, pretreatment of LLC cells with ceramide/DMS not only increased the protein expression level of Bax, but also decreased Bcl-2 after gamma-irradiation. Taken together, the present study indicates that the radiosensitizing activity of ceramide/DMS on LLC cells most likely reflects the dominance of pro-apoptotic signals related to the mitochondria-dependent pathway.
Animals ; Apoptosis/drug effects ; Carcinoma, Lewis Lung/metabolism/*radiotherapy ; Caspases/metabolism ; Cell Line, Tumor ; Cell Survival/drug effects/radiation effects ; Gene Expression ; Lung Neoplasms/metabolism/*radiotherapy ; Mice ; Proto-Oncogene Proteins/genetics/metabolism ; Proto-Oncogene Proteins c-bcl-2/genetics/metabolism ; Radiation Tolerance ; *Radiation-Sensitizing Agents ; Research Support, Non-U.S. Gov't ; Sphingosine/*analogs & derivatives/pharmacology/*therapeutic use

Melanoma is the most aggressive skin cancer and its incidence is gradually increasing worldwide. Patients with metastatic melanoma have a very poor prognosis (estimated 5-year survival rate of <16%). In the last few years, several drugs have been approved for malignant melanoma, such as tyrosine kinase inhibitors and immune checkpoint blockades. Although new therapeutic agents have improved progression-free and overall survival, their use is limited by drug resistance and drug-related toxicity. At the same time, adoptive cell therapy of metastatic melanoma with tumor-infiltrating lymphocytes has shown promising results in preclinical and clinical studies. In this review, we summarize the currently available drugs for treatment of malignant melanoma. In addition, we suggest cytokine-induced killer (CIK) cells as another candidate approach for adoptive cell therapy of melanoma. Our preclinical study and several previous studies have shown that CIK cells have potent anti-tumor activity against melanomas in vitro and in an in vivo human tumor xenograft model without any toxicity.
Cell- and Tissue-Based Therapy* ; Cytokine-Induced Killer Cells* ; Drug Resistance ; Heterografts ; Humans ; Incidence ; Lymphocytes, Tumor-Infiltrating ; Melanoma* ; Prognosis ; Protein-Tyrosine Kinases ; Skin Neoplasms ; Survival Rate

Colorectal cancer is the third leading cancer worldwide. Although incidence and mortality of colorectal cancer are gradually decreasing in the US, patients with metastatic colorectal cancer have poor prognosis with an estimated 5-year survival rate of less than 10%. Over the past decade, advances in combination chemotherapy regimens for colorectal cancer have led to significant improvement in progression-free and overall survival. However, patients with metastatic disease gain little clinical benefit from conventional therapy, which is associated with grade 3~4 toxicity with negative effects on quality of life. In previous clinical studies, cell-based immunotherapy using dendritic cell vaccines and sentinel lymph node T cell therapy showed promising therapeutic results for metastatic colorectal cancer. In our preclinical and previous clinical studies, cytokine-induced killer (CIK) cells treatment for colorectal cancer showed favorable responses without toxicities. Here, we review current treatment options for colorectal cancer and summarize available clinical studies utilizing cell-based immunotherapy. Based on these studies, we recommend the use CIK cell therapy as a promising therapeutic strategy for patients with metastatic colorectal cancer.
Cell- and Tissue-Based Therapy ; Colorectal Neoplasms* ; Cytokine-Induced Killer Cells* ; Dendritic Cells ; Drug Therapy, Combination ; Humans ; Immunotherapy* ; Incidence ; Lymph Nodes ; Mortality ; Prognosis ; Quality of Life ; Survival Rate ; Vaccines

PURPOSE: Radiation-induced pulmonary fibrosis (RIF) is a significant complication of radiotherapy for lung cancer. Despite the large number of studies, the molecular mechanisms of RIF are poorly understood. Therefore, the complex protein expression pattern in RIF was characterized by identifying the proteins with an altered expression level after thorax irradiation using two-dimensional electrophoresis (2-DE) and mass spectrometry. MATERIALS AND METHODS: A mouse model of RIF was used to examine the alteration of the lung proteome because of availability of murine data related to human cases and the abundance of murine fibrotic lung samples. A mouse model of RIF was induced in radiosensitive C57BL/6 mice. Twenty-one weeks after 25 Gy irradiation, hematoxylin-eosin staining and hydroxyproline assay confirmed the early-phase pulmonary fibrosis. RESULTS: Lung samples from the irradiated and age-matched control mice were used to generate 16 high quality 2-DE gels containing approximately 1,000 spots. Of the 31 significantly up- or down-regulated protein spots, 17 were identified by MALDI-TOF/MS. CONCLUSIONS: Two important upregulated proteins were found, the alpha-protease inhibitor and galectin-1, which might be used as potential markers for the early phase of RIF.
Animals ; Electrophoresis ; Galectin 1* ; Gels ; Humans ; Hydroxyproline ; Lung ; Lung Neoplasms ; Mass Spectrometry ; Mice ; Proteome ; Proteomics ; Pulmonary Fibrosis* ; Radiotherapy ; Thorax