Hycanthone Inhibits Inflammasome Activation and Neuroinflammation-Induced Depression-Like Behaviors in Mice

Despite the various medications used in clinics, the efforts to develop more effective treatments for depression continue to increase in the past decades mainly because of the treatment-resistant population, and the testing of several hypotheses- and target-based treatments. Undesirable side effects and unresponsiveness to current medications fuel the drive to solve this top global health problem. In this study, we focused on neuroinflammatory response-mediated depression which represents a cluster of depression etiology both in animal models and humans. Several meta-analyses reported that proinflammatory cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were increased in major depressive disorder patients. Inflammatory mediators implicated in depression include type-I interferon and inflammasome pathways. To elucidate the molecular mechanisms of neuroinflammatory cascades underlying the pathophysiology of depression, we introduced hycanthone, an antischistosomal drug, to check whether it can counteract depressive-like behaviors in vivo and normalize the inflammation-induced changes in vitro. Lipopolysaccharide (LPS) treatment increased proinflammatory cytokine expression in the murine microglial cells as well as the stimulation of type I interferon-related pathways that are directly or indirectly regulated by Janus kinase-signal transducer and activator of transcription (JAK-STAT) activation. Hycanthone treatment attenuated those changes possibly by inhibiting the JAK-STAT pathway and inflammasome activation. Hycanthone also ameliorated depressive-like behaviors by LPS. Taken together, we suggest that the inhibitory action of hycanthone against the interferon pathway leading to attenuation of depressive-like behaviors can be a novel therapeutic mechanism for treating depression.

Evolutionary and Comparative Genomics to Drive Rational Drug Design, with Particular Focus on Neuropeptide Seven-Transmembrane Receptors

Seven transmembrane receptors (7TMRs), also known as G protein-coupled receptors, are popular targets of drug development, particularly 7TMR systems that are activated by peptide ligands. Although many pharmaceutical drugs have been discovered via conventional bulk analysis techniques the increasing availability of structural and evolutionary data are facilitating change to rational, targeted drug design. This article discusses the appeal of neuropeptide-7TMR systems as drug targets and provides an overview of concepts in the evolution of vertebrate genomes and gene families. Subsequently, methods that use evolutionary concepts and comparative analysis techniques to aid in gene discovery, gene function identification, and novel drug design are provided along with case study examples.

A Novel Long-Acting Glucagon-Like Peptide-1 Agonist with Improved Efficacy in Insulin Secretion and beta-Cell Growth

BACKGROUND: Glucagon-like peptide-1 (GLP-1) is an incretin hormone produced by cleavage of proglucagon in intestinal L-cells. In the pancreas, GLP-1 stimulates post-prandial insulin secretion, promotes insulin biosynthesis, and improves insulin sensitivity. Because of its insulinotropic activity, GLP-1 has been considered a good candidate drug for treatment of diabetes mellitus. However, clinical use of GLP-1 has been limited by its short half-life, as a result of rapid degradation by dipeptidyl peptidase-IV (DPP-IV). METHODS: We designed a novel GLP-1 analog, Xenopus GLP-1 (xGLP)-E4. The Ala residue in the second position of xGLP was replaced with a Ser residue to increase the half-life in the body. The C-terminal tail of exendin-4 was added to enhance the binding affinity for the GLP-1 receptor (GLP1R). The potency of GLP-1 and its analogs was determined by luciferase assay. The stability of GLP1R agonists was evaluated by determining the activity of agonists that had been preincubated in the presence of fetal bovine serum, which contains innate DPP-IV activity. The effects of xGLP-E4 on insulin secretion and beta-cell growth were investigated using insulin enzyme-linked immunosorbent assay and cell counting. RESULTS: xGLP-E4 exhibited improved stability against DPP-IV activity and increased potency to GLP1R, compared with GLP-1. An increase in glucose-dependent insulin secretion was observed in xGLP-E4-treated pancreatic beta-cells. The effect of xGLP-E4 on beta-cell growth was greater than that of GLP-1. CONCLUSION: We developed a novel GLP-1 analog, xGLP-E4, that shows prolonged longevity and improved efficacy. This analog is a potential candidate for treatment of type 2 diabetes.

Physiological Function of G Protein-Coupled Receptors(GPCRs) and Research Trends for Orphan GPCRs / 대한내분비학회지

No abstract available.

Physiological Function of G Protein-Coupled Receptors(GPCRs) and Research Trends for Orphan GPCRs / 대한내분비학회지

No abstract available.

GnRH pre-mRNA Splicing in Hypogonadal Mice / 대한소아내분비학회지

No abstract available.

Atypical Eruption Due to Chemotherapeutic Agent

We report a case of atypical eruption due to chemotherapeutic agent in a 60-year-old man who presented with asymptomatic, erythematous, 0.5cm in diameter, confluent, and elevated papules and plaques confined to the face. The patient was previously diagnosed with small cell carcinoma of the lung with liver metastasis. Two months after the diagnosis, a first course of chemotherapy including etoposide was started. Five days after starting the chemotherapy, the patient developed a facial eruption. Histopathologic examination demonstrated increased epidermal mitotic figures, cells in metaphase arrest, basal cell layer hyperpigmentation, prominent dyskeratosis, and squamous atypia. The most distinctive histologic feature was the presence of starburst cells, which are markedly enlarged pale staining keratinocytes containing small basophilic fragments of nuclear debris haphazardly scattered throughout the cytoplasm in a starburst pattern.

Plaque stage of Dermatofibrosarcoma Protuberans / 대한피부과학회지

We report a case of plaque stage of dermatofibrosarcoma protuberans(DFSP). A 36-year-old female visited our clinic with a 10-year history of solitary deep seated palpable erythematous plaque on right anterior chest. There was no history of previous trauma at the site of the lesion. Histopathologic findings are characterized by a flat surface, lower cellularity and slender spindle-shaped neoplastic cells diffusely infiltrated dermis and subcutaneous tissue. The slender neoplastic cells have uniform nuclei with no evidence of cytologic atypia. Especially earlier plaque or nonprotuberans stage of the DFSP could be confused with benign lesions such as dermatofibroma or diffuse neurofibroma. Because plaque areas are strongly positive for CD34, this antibody is very helpful in differentiating other benign tumors.

A Case of Verrucous Hyperplasia with Lymphedema of the Leg Amputation Stump / 대한피부과학회지

Verrucous hyperplasia shows multiple warty like lesion on the amputation stump, but the pathologic findings of viral verrucae has not been discovered. A verrucous plaque on the amputation stump of the right leg was found in 31-year-old man. He had suffered from a traumatic amputation of right leg since 8 years ago. A leg prosthesis had been worn since that time. Histopathologic findings shows hyperkeratosis, acanthosis, papillomatosis, superficial dermal edema and dilated thick-walled venules oriented vertical to the skin surface. Verrucous hyperplasia was diagnosed with lymphedema on the basis of clinical and histological findings.

Mycosis Fungoides in Children: Clinical Feature of 14 Patients / 대한피부과학회지

BACKGROUND: Mycosis fungoides(MF) is a representative of cutaneous T cell lymphoma and progresses through clinical stages, such as initial pre-mycotic(macule or patch), plaque, and tumor stage. MF is usually thought of as a disease of old adults, but it can develop at any age, including childhood. Despite the recognition that MF may occur in pediatric patients, there is scant literature regarding clinical feature, histopathologic finding and prognosis specially related to childhood onset. The purpose of this study was to examine the clinical, histopathologic and follow up observation of MF in children. METHODS:This study has been reviewed in the clinicopathologic findings of 14 MF patients who visited the Kosin University Gospel Hospital during about 10 years from January, 1991 to June, 2000. RESULTS: 1.Duration of cutaneous lesions was from 6 months to 10 years, with mean duration of 3.6 years. 2.The morphology of skin lesions showed various features(pityriasis lichenoides-like, hypopigmented, hyperpigmented, ichthyosis-like, inflammatory linear verrucous epidermal nevus-like). 3. Histopathologic features revealed epidermotropism, a perivascular infiltrate in all cases, haloed lymphocytes, lymphocytes aligned in the basal layer, and coarse collagen in the papillary dermis in most cases. Pautrier's microabscess was shown in 3 cases(23%). 4. In T cell receptor gamma gene arrangement using PCR(polymerase chain reaction), monoclonality was detected in 13 out of 14(93%). 5. Treatment including PUVA(psoralen and UVA), UVB, topical steroid agents and calcipotriol had good a response. 6. No patients had progressed to a more advanced disease. CONCLUSION: MF in children of this study showed a wide variety of skin lesions. Although no case of MF in this study progressed to a more aggressive status, MF in children should be carefully followed for development of more advanced cutaneous lesions and visceral involvement.

Mycosis Fungoides in Children: Clinical Feature of 14 Patients / 대한피부과학회지

BACKGROUND: Mycosis fungoides(MF) is a representative of cutaneous T cell lymphoma and progresses through clinical stages, such as initial pre-mycotic(macule or patch), plaque, and tumor stage. MF is usually thought of as a disease of old adults, but it can develop at any age, including childhood. Despite the recognition that MF may occur in pediatric patients, there is scant literature regarding clinical feature, histopathologic finding and prognosis specially related to childhood onset. The purpose of this study was to examine the clinical, histopathologic and follow up observation of MF in children. METHODS:This study has been reviewed in the clinicopathologic findings of 14 MF patients who visited the Kosin University Gospel Hospital during about 10 years from January, 1991 to June, 2000. RESULTS: 1.Duration of cutaneous lesions was from 6 months to 10 years, with mean duration of 3.6 years. 2.The morphology of skin lesions showed various features(pityriasis lichenoides-like, hypopigmented, hyperpigmented, ichthyosis-like, inflammatory linear verrucous epidermal nevus-like). 3. Histopathologic features revealed epidermotropism, a perivascular infiltrate in all cases, haloed lymphocytes, lymphocytes aligned in the basal layer, and coarse collagen in the papillary dermis in most cases. Pautrier's microabscess was shown in 3 cases(23%). 4. In T cell receptor gamma gene arrangement using PCR(polymerase chain reaction), monoclonality was detected in 13 out of 14(93%). 5. Treatment including PUVA(psoralen and UVA), UVB, topical steroid agents and calcipotriol had good a response. 6. No patients had progressed to a more advanced disease. CONCLUSION: MF in children of this study showed a wide variety of skin lesions. Although no case of MF in this study progressed to a more aggressive status, MF in children should be carefully followed for development of more advanced cutaneous lesions and visceral involvement.

Molecular Mechanism of GnRH Interaction with GnRH Receptor in an Evolutionary Viewpoint / 대한내분비학회지

No Abstract Available.

A Case of Pigmented Spindle Cell Nevus / 대한피부과학회지

We report a case of pigmented spindle cell nevus which occurred in a 4-year-old male. Several months earlier, his mother noticed a 3x3mm sized annular, hyperpigmented macule on his right thigh. Histopathologic findings showed nests of spindle cells with sharply defined lateral margins in the dermoepidermal junction and cleft around the spindle cell nests with heavy melanin pigmentation.