Chemical Constituents Identified from Fruit Body of Cordyceps bassiana and Their Anti-Inflammatory Activity

Cordyceps bassiana is one of Cordyceps species with anti-oxidative, anti-cancer, anti-inflammatory, anti-diabetic, anti-obesity, anti-angiogenic, and anti-nociceptive activities. This mushroom has recently demonstrated to have an ability to reduce 2,4-dinitrofluorobenzene-induced atopic dermatitis symptoms in NC/Nga mice. In this study, we further examined phytochemical properties of this mushroom by column chromatography and HPLC analysis. By chromatographic separation and spectroscopic analysis, 8 compounds, such as 1,9-dimethylguanine (1), adenosine (2), uridine (3), nicotinamide (4), 3-methyluracil (5), 1,7-dimethylxanthine (6), nudifloric acid (7), and mannitol (8) were identified from 6 different fractions and 4 more subfractions. Through evaluation of their anti-inflammatory activities using reporter gene assay and mRNA analysis, compound 1 was found to block luciferase activity induced by NF-κB and AP-1, suppress the mRNA levels of cyclooxygenase (COX)-2 and tumor necrosis factor (TNF)-α. Therefore, our data strongly suggests that compound 1 acts as one of major principles in Cordyceps bassiana with anti-inflammatory and anti-atopic dermatitis activities.

Hydroquinone suppresses IFN-β expression by targeting AKT/IRF3 pathway

Previous studies have demonstrated the role of hydroquinone (HQ), a hydroxylated benzene metabolite, in modulating various immune responses; however, its role in macrophage-mediated inflammatory responses is not fully understood. In this study, the role of HQ in inflammatory responses and the underlying molecular mechanism were explored in macrophages. HQ down-regulated the expression of interferon (IFN)-β mRNA in LPS-stimulated RAW264.7 cells without any cytotoxicity and suppressed interferon regulatory factor (IRF)-3-mediated luciferase activity induced by TIR-domain-containing adapter-inducing interferon-β (TRIF) and TANK-binding kinase 1 (TBK1). A mechanism study revealed that HQ inhibited IRF-3 phosphorylation induced by lipopolysaccharide (LPS), TRIF, and AKT by suppressing phosphorylation of AKT, an upstream kinase of the IRF-3 signaling pathway. IRF-3 phosphorylation is highly induced by wild-type AKT and poorly induced by an AKT mutant, AKT C310A, which is mutated at an inhibitory target site of HQ. We also showed that HQ inhibited IRF-3 phosphorylation by targeting all three AKT isoforms (AKT1, AKT2, and AKT3) in RAW264.7 cells and suppressed IRF-3-mediated luciferase activities induced by AKT in HEK293 cells. Taken together, these results strongly suggest that HQ inhibits the production of a type I IFN, IFN-β, by targeting AKTs in the IRF-3 signaling pathway during macrophage-mediated inflammation.

Changes in Oral Vowel Sounds and Hyoid Bone Movement After Thyroidectomy

OBJECTIVES: Voice and speech alterations after total thyroidectomy may be associated with other extralaryngeal factors, such as neck muscle dysfunction and neck scar contracture. We evaluated the acoustic characteristics of oral vowel sounds and changes in hyoid bone movement before and after thyroidectomy. METHODS: Twenty-nine female patients undergoing total thyroidectomy were included. Fundamental frequencies (Fo), formants and vowel space areas were evaluated before surgery and 7 days and 3 months after surgery to acoustically analyze the oral vowel sounds. Videofluoroscopic images were taken at the same times to evaluate hyoid bone movement. RESULTS: The Fo levels of seven vowels decreased significantly after surgery. The vowel formant changes the F1 of vowel /[e]/ decreased significantly from baseline at 3 months postoperatively, and the F3 of vowel /[i]/ decreased significantly from baseline 7 days postoperatively. The change in the vowel space area was not observed. The Y coordinate of the vowels /[i]/ and /[e]/ decreased significantly from baseline 7 days postoperatively due to changes in hyoid movement. CONCLUSION: The damage to the neck muscles after thyroidectomy changes in Fo, formant and hyoid bone position. These quantitative results could be used as basic data for voice management in patients who undergo thyroidectomy.

Anti-Proliferative and Pro-Apoptotic Activities of 4-Methyl-2,6-bis(1-phenylethyl)phenol in Cancer Cells

It has been found that 4-isopropyl-2,6-bis(1-phenylethyl)phenol (KTH-13), a novel compound isolated from Cordyceps bassiana, is able to suppress tumor cell proliferation by inducing apoptosis. To mass-produce this compound, we established a total synthesis method. Using those conditions, we further synthesized various analogs with structural similarity to KTH-13. In this study, we aimed to test their anti-cancer activity by measuring anti-proliferative and pro-apoptotic activities. Of 8 compounds tested, 4-methyl-2,6-bis(1-phenylethyl)phenol (KTH-13-Me) exhibited the strongest anti-proliferative activity toward MDA-MB 231 cells. KTH-13-Me also similarly suppressed the survival of various cancer cell lines, including C6 glioma, HCT-15, and LoVo cells. Treatment of KTH-13-Me induced several apoptotic signs in C6 glioma cells, such as morphological changes, induction of apoptotic bodies, and nuclear fragmentation and chromatin condensation. Concordantly, early-apoptotic cells were also identified by staining with FITC-Annexin V/PI. Moreover, KTH-13-Me highly enhanced the activation of caspase-3 and caspase-9, and decreased the protein level of Bcl-2. In addition, the phosphorylation levels of Src and STAT3 were diminished in KTH-13-Me-treated C6 cells. Therefore, these results suggest that KTH-13-Me can be developed as a novel anti-cancer drug capable of blocking proliferation, inducing apoptosis, and blocking cell survival signaling in cancer cells.

Restless Legs Syndrome in Children and Adolescents with Type 1 Diabetes / 수면정신생리

OBJECTIVES: Restless legs syndrome (RLS) is a common sleep disorder in adults with diabetes. This study investigated the frequency of RLS and clinical correlations in children and adolescents with type 1 diabetes. METHODS: This study included 55 consecutive patients (21 males, age 12.6 +/- 3.4 years) with type I diabetes that were regularly treated at the Department of Pediatric Endocrinology. RLS was diagnosed by intensive interviews which also included the Epworth Sleepiness Scale (ESS) and International RLS Rating Scale (IRLSRS). Patients also received neurological examinations and laboratory tests for diabetes, iron metabolism and renal function. RESULTS: Thirteen patients (23.6%, 6 males) were compatible for the diagnostic criteria of RLS. None of the RLS patients showed abnormal findings in neurological evaluations and 7 patients had familial history of RLS. Demographic and laboratory findings were not different between the patients with or without RLS. The RLS group showed significantly increased ESS and IRLSRS scores. CONCLUSION: RLS was prevalent in children and adolescents with type I diabetes. The association between RLS and diabetes-related laboratory findings requires further investigation.

A Case of Posthypoxic Myoclonus with Lamotrigine Add-On Therapy / 대한간질학회지

Posthypoxic myoclonus is poorly controlled with current treatments. Based on clinical experience, valproate and benzodiazepines have been used to treat myoclonic seizures. Rarely, some antiepileptic drugs may exacerbate myoclonic seizures. Although lamotrigine is controversial for treatment in myoclonic seizures, we experience a case of posthypoxic myoclonus improved with lamotrigine add-on therapy.