Sarcomatoid carcinoma is rarely diagnosed as gallbladder cancer. Its aggressive nature, due to the characteristics of both sarcoma and carcinoma, results in a poor prognosis. We report a case of gallbladder sarcomatoid carcinoma in an 82-year-old male who was referred to our hospital for evaluation of gallbladder cancer observed on abdominopelvic computed tomography. The characteristics of the cancer were not confirmed after several imaging modalities. The surgically resected tumor was positive for both cytokeratin and vimentin as revealed via immunohistochemical staining, and a sarcomatoid carcinoma was finally diagnosed. The role of chemotherapy has not yet been identified. Therefore, radiation therapy is planned to reduce the risk of recurrence.

Background: Increased sebum secretion is considered the main causative factor in the pathogenesis of acne. There is an unmet pharmacological need for a novel drug that can control sebum production with a favorable adverse effect profile. Objective: To investigate the effect of azidothymidine on lipid synthesis in sebocytes and to identify the underlying mechanism of the inhibitory effect of azidothymidine on insulin-like growth factor (IGF)-1-induced lipid synthesis in sebocytes. Methods: Immortalized human sebocytes were used for the analysis. Thin-layer chromatography (TLC) and Oil Red O staining were performed to evaluate lipid synthesis in the sebocytes. The differentiation, lipid synthesis, mitochondrial biogenesis, and mitophagy in sebocytes were investigated. Results: TLC and Oil Red O staining revealed that azidothymidine reduced IGF-1 induced lipid synthesis in the immortalized human sebocytes. Azidothymidine also reduced IGF-1-induced expression of transcriptional factors and enzymes involved in sebocyte differentiation and lipid synthesis, respectively. Moreover, we found that IGF-1 upregulated the levels of peroxisome proliferator-activated receptor-gamma coactivator-1α, LC-3B, p62, and Parkin, major regulators of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. In contrast, azidothymidine inhibited IGF-1 induced mitochondrial biogenesis and mitophagy in the sebocytes. Conclusion These results suggest that azidothymidine downregulates IGF-1-induced lipogenesis by dysregulating the quality of mitochondria through suppression of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. Our study provides early evidence that azidothymidine may be an effective candidate for a new pharmacological agent for controlling lipogenesis in sebocytes.

Background: Increased sebum secretion is considered the main causative factor in the pathogenesis of acne. There is an unmet pharmacological need for a novel drug that can control sebum production with a favorable adverse effect profile. Objective: To investigate the effect of azidothymidine on lipid synthesis in sebocytes and to identify the underlying mechanism of the inhibitory effect of azidothymidine on insulin-like growth factor (IGF)-1-induced lipid synthesis in sebocytes. Methods: Immortalized human sebocytes were used for the analysis. Thin-layer chromatography (TLC) and Oil Red O staining were performed to evaluate lipid synthesis in the sebocytes. The differentiation, lipid synthesis, mitochondrial biogenesis, and mitophagy in sebocytes were investigated. Results: TLC and Oil Red O staining revealed that azidothymidine reduced IGF-1 induced lipid synthesis in the immortalized human sebocytes. Azidothymidine also reduced IGF-1-induced expression of transcriptional factors and enzymes involved in sebocyte differentiation and lipid synthesis, respectively. Moreover, we found that IGF-1 upregulated the levels of peroxisome proliferator-activated receptor-gamma coactivator-1α, LC-3B, p62, and Parkin, major regulators of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. In contrast, azidothymidine inhibited IGF-1 induced mitochondrial biogenesis and mitophagy in the sebocytes. Conclusion These results suggest that azidothymidine downregulates IGF-1-induced lipogenesis by dysregulating the quality of mitochondria through suppression of mitochondrial biogenesis and mitophagy in immortalized human sebocytes. Our study provides early evidence that azidothymidine may be an effective candidate for a new pharmacological agent for controlling lipogenesis in sebocytes.

Background: Psoriasis is a common chronic inflammatory skin disease. The development of psoriasis is dependent on many intercellular events such as innate immunity and T cell-mediated inflammation. Furthermore, genetic factors are strongly implicated in the pathophysiology of psoriasis. Although a variety of susceptible genes are identified, it is likely that many important genes remain undisclosed. Objective: The aim of this study is to investigate the possible role of lysine demethylase 2A (KDM2A) in the pathophysiology of psoriasis. Methods: We examined the expression of KDM2A using a well established imiquimod-induced psoriasiform dermatitis model. Results: Immunohistochemistry analysis showed that expression of KDM2A was increased in imiquimod-induced psoriasiform dermatitis. Consistent with this result, KDM2A level was markedly increased in the epidermis of psoriatic patient. When keratinocytes were stimulated with TLR3 agonist poly(I:C), KDM2A was increased at both the mRNA and protein levels. Poly(I:C) increased the expression of psoriasis-related cytokines including tumor necrosis factor-α, interleukin-8, and CCL20, and KDM2A inhibitor daminozide enhanced the poly(I:C)-induced cytokine expression. Finally, topical co-application of imiquimod and daminozide exacerbated the imiquimod-induced psoriasiform dermatitis. Conclusion Together, these results suggest that KDM2A is increased to negatively regulate the inflammatory reaction of epidermal keratinocytes in psoriasis.

Background: Female-pattern hair loss (FPHL) is a common hair loss disorder in women. The various treatments include topical minoxidil and 17α-estradiol, as well as oral anti-androgens. However, the clinical efficacy of 5α -reductase inhibitors remains controversial. Objective: We evaluated the clinical utility of dutasteride in FPHL patients and how dutasteride promotes hair growth. Methods: We evaluated hair follicle density and thickness before and after oral dutasteride treatment in 24 patients with FPHL. We measured β-catenin activity in primary cultures of human dermal papilla cells (DPCs) using the TOP Flash reporter assay and Western blotting. The expression levels of genes promoting hair growth were quantitatively assessed using quantitative polymerase chain reaction (Q-PCR). Results: The mean vertex hair density increased significantly from 67±14 to 76±13/cm2 (p=0.001) and the mean occipital hair density increased from 89±11 to 94±13/cm2 (p=0.012) after dutasteride treatment. However, the mean hair thickness did not increase. When DPCs were treated with dutasteride, TOP Flash activity increased in a dose-dependent manner, and the protein level of non-phosphorylated (active) β-catenin also increased. The mRNA level of vascular endothelial growth factor increased, but the mRNA levels of the keratinocyte growth factor, insulin growth factor-1, and Noggin were not affected by dutasteride. Conclusion This study shows a novel mechanism of dutasteride in promoting hair growth and provides support for the possible clinical application of 5α-reductase inhibitors for the treatment of FPHL.

Two-point mutations (V419L and L925I) on the voltage-sensitive sodium channel of bed bugs (Cimex lectularius) are known to confer pyrethroid resistance. To determine the status of pyrethroid resistance in bed bugs in Korea, resistance allele frequencies of bed bug strains collected from several US military installations in Korea and Mokpo, Jeollanamdo, from 2009-2019 were monitored using a quantitative sequencing. Most bed bugs were determined to have both of the point mutations except a few specimens, collected in 2009, 2012 and 2014, having only a single point mutation (L925I). No susceptible allele was observed in any of the bed bugs examined, suggesting that pyrethroid resistance in bed bug populations in Korea has reached a serious level. Large scale monitoring is required to increase our knowledge on the distribution and prevalence of pyrethroid resistance in bed bug populations in Korea. Based on present study, it is urgent to restrict the use of pyrethroids and to introduce effective alternative insecticides. A nation-wide monitoring program to determine the pyrethroid resistance level in bed bugs and to select alternative insecticides should be implemented.

BACKGROUND: Psoriasis is a chronic inflammatory skin disease with an incidence of 0.5~3% of the worldwide population. The pathogenesis of psoriasis is related to dysregulated keratinocyte function and immune reactions. Notably, genetic factors are considered important etiological contributors. Globally, several researchers have recently performed genome-wide association studies (GWAS) to identify the genes related with psoriasis. OBJECTIVE: We aimed to investigate the expression pattern of 2 candidate genes that were identified by GWAS. These include interleukin 28 receptor alpha (IL28RA) and CUB and Sushi multiple domains 1 (CSMD1). METHODS: We applied imiquimod cream to develop a psoriasis-like mouse model and obtained skin tissue. We performed immunohistochemistry to detect the expression of IL-28A and CSMD1. RESULTS: IL28RA expression increased at an early time point such as 1 day after the topical application of 5% imiquimod cream. However, its expression returned to baseline levels 2 weeks after the topical application of imiquimod cream. CSMD1 expression also increased after the topical application of imiquimod, with increased expression particularly observed in the upper epidermal layer. Notably, CSMD1 expression decreased 7 days after imiquimod cream application. CONCLUSION: These results suggest that IL28RA and CSMD1 may play key roles in the pathogenesis of psoriasis.
Animals ; Gene Expression* ; Genome-Wide Association Study ; Immunohistochemistry ; Incidence ; Interleukins ; Keratinocytes ; Mice* ; Psoriasis ; Skin ; Skin Diseases

Fetal DNA (fDNA) detection in maternal serum is a challenge due to low copy number and the smaller size of fDNA fragments compared to DNA fragments derived from the mother. Massively parallel sequencing (MPS) is a useful technique for fetal genetic analysis that is able to detect and quantify small amounts of DNA. In this study, seven clinical samples of maternal serum potentially containing fDNA were analyzed with a commercial single nucleotide polymorphism (SNP) panel, the HID-Ion AmpliSeq™ Identity Panel, and the results were compared to those from previous studies. Reference profiles for mothers and fetuses were not available, but multiple Y chromosomal SNPs were detected in two samples, indicating that fDNA was present in the serum and thereby validating observations of autosomal SNPs. This suggests that SNP-based MPS can be valuable for fDNA detection, thereby offering an insight into fetal genetic status. This technology could also be used to detect small amounts of DNA in mixed DNA samples for forensic applications.
DNA* ; Fetus ; High-Throughput Nucleotide Sequencing ; Humans ; Mothers ; Polymorphism, Single Nucleotide

BACKGROUND: Psoriasis is characterized by uncontrolled hyperproliferation, aberrant differentiation, and dermal infiltration of immune cells. Recent studies have reported that Wnt5a and Notch1 signaling are altered in psoriatic skin lesions. OBJECTIVE: We aimed to investigate the interaction of Wnt5a with Notch 1 with respect to inflammation-mediated epidermal hyperproliferation in psoriasis. METHODS: Expression of Wnt5a and Notch1 signaling-related proteins were examined in psoriatic skin biopsies. Wnt5a was upregulated in human keratinocytes by treating the cells with its recombinant form (rWnt5a). RESULTS: In psoriatic lesions, expression of Wnt5a increased while that of Notch1 decreased when compared to that in non-lesional and normal skin. Treatment with rWnt5a increased the proliferation of keratinocytes and increased their secretion of interleukin (IL)-23, IL-12, and tumor necrosis factor (TNF)-alpha. Further, exposure of keratinocytes to IL-1alpha, TNF-alpha, transforming growth factor-alpha, and interferon-gamma downregulated Notch1 as well as HES 1, which is downstream to Notch1, but increased the Wnt5a levels. The upregulated Wnt5a in keratinocytes downregulated both Notch1 and HES1. CONCLUSION: Our data suggest that Wnt5a and Notch1 signaling exert counteracting influences on each other and are involved, in part, in the pathomechanism of psoriasis.
Biopsy ; Humans ; Interferon-gamma ; Interleukin-12 ; Interleukins ; Keratinocytes ; Psoriasis* ; Skin ; Tumor Necrosis Factor-alpha

A total of 1,708 small mammals (1,617 rodents and 91 soricomorphs), including Apodemus agrarius (n = 1,400), Microtus fortis (167), Crocidura lasiura (91), Mus musculus (32), Myodes (= Eothenomys) regulus (9), Micromys minutus (6), and Tscherskia (= Cricetulus) triton (3), were live-trapped at US/Republic of Korea (ROK) military training sites near the demilitarized zone (DMZ) of Paju, Pocheon, and Yeoncheon, Gyeonggi Province from December 2004 to December 2009. Small mammals were examined for their intestinal nematodes by necropsy. A total of 1,617 rodents (100%) and 91 (100%) soricomorphs were infected with at least 1 nematode species, including Nippostrongylus brasiliensis, Heligmosomoides polygyrus, Syphacia obvelata, Heterakis spumosa, Protospirura muris, Capillaria spp., Trichuris muris, Rictularia affinis, and an unidentified species. N. brasiliensis was the most common species infecting small mammals (1,060; 62.1%) followed by H. polygyrus (617; 36.1%), S. obvelata (370; 21.7%), H. spumosa (314; 18.4%), P. muris (123; 7.2%), and Capillaria spp. (59; 3.5%). Low infection rates (0.1-0.8%) were observed for T. muris, R. affinis, and an unidentified species. The number of recovered worms was highest for N. brasiliensis (21,623 worms; mean 20.4 worms/infected specimen) followed by S. obvelata (9,235; 25.0 worms), H. polygyrus (4,122; 6.7 worms), and H. spumosa (1,160; 3.7 worms). A. agrarius demonstrated the highest prevalence for N. brasiliensis (70.9%), followed by M. minutus (50.0%), T. triton (33.3%), M. fortis (28.1%), M. musculus (15.6%), C. lasiura (13.2%), and M. regulus (0%). This is the first report of nematode infections in small mammals captured near the DMZ in ROK.
Animals ; Animals, Wild ; Female ; Helminthiasis/epidemiology/parasitology ; Helminths/*classification/*isolation & purification ; Insectivora/*parasitology ; Intestinal Diseases, Parasitic/epidemiology/parasitology/*veterinary ; Intestines/parasitology ; Male ; Prevalence ; Republic of Korea/epidemiology ; Rodentia/*parasitology