NKT cells promote antibody-induced joint inflammation by suppressing transforming growth factor β1 production

Although NKT cells has been known to exert protective roles in the development of autoimmune diseases, the functional roles of NKT cells in the downstream events of antibody-induced joint inflammation remain unknown. Thus, we explored the functional roles of NKT cells in antibody-induced arthritis using the K/BxN serum transfer model. NKT cell–deficient mice were resistant to the development of arthritis, and wild-type mice administrated with α-galactosyl ceramide, a potent NKT cell activator, aggravated arthritis. In CD1d−/− mice, transforming growth factor (TGF)-β1 was found to be elevated in joint tissues, and the blockade of TGF-β1 using neutralizing monoclonal antibodies restored arthritis. The administration of recombinant TGF-β1 into C57BL/6 mice reduced joint inflammation. Moreover, the adoptive transfer of NKT cells into CD1d−/− mice restored arthritis and reduced TGF-β1 production. In vitro assay demonstrated that interleukin (IL)-4 and interferon (IFN)-γ were involved in suppressing TGF-β1 production in joint cells. The adoptive transfer of NKT cells from IL-4−/− or IFN-γ−/− mice did not reverse arthritis and TGF-β1 production in CD1d−/− mice. In conclusion, NKT cells producing IL-4 and IFN-γ play a role in immune complex–induced joint inflammation by regulating TGF-β1

Linear programming method to construct equated item sets for the implementation of periodical computer-based testing for the Korean Medical Licensing Examination

Purpose This study aimed to identify the best way of developing equivalent item sets and to propose a stable and effective management plan for periodical licensing examinations. Methods Five pre-equated item sets were developed based on the predicted correct answer rate of each item using linear programming. These pre-equated item sets were compared to the ones that were developed with a random item selection method based on the actual correct answer rate (ACAR) and difficulty from item response theory (IRT). The results with and without common items were also compared in the same way. ACAR and the IRT difficulty were used to determine whether there was a significant difference between the pre-equating conditions. Results There was a statistically significant difference in IRT difficulty among the results from different pre-equated conditions. The predicted correct answer rate was divided using 2 or 3 difficulty categories, and the ACAR and IRT difficulty parameters of the 5 item sets were equally constructed. Comparing the item set conditions with and without common items, including common items did not make a significant contribution to the equating of the 5 item sets. Conclusion This study suggested that the linear programming method is applicable to construct equated-item sets that reflect each content area. The suggested best method to construct equated item sets is to divide the predicted correct answer rate using 2 or 3 difficulty categories, regardless of common items. If pre-equated item sets are required to construct a test based on the actual data, several methods should be considered by simulation studies to determine which is optimal before administering a real test

The Effect of Calcipotriol on the Expression of Human β Defensin-2 and LL-37 in Cultured Human Keratinocytes

Background. Vitamin D has been reported to regulate innate immunity by controlling the expression of antimicrobial peptides (AMPs). Objective. We investigated the effect of calcipotriol on the expression of AMPs in human cultured keratinocytes. Methods. Keratinocytes were treated with lipopolysaccharide (LPS), TNF-α, Calcipotriol and irradiated with UVB, cultured, and harvested. To assess the expression of human beta defensin-2 and LL-37 in the control group, not exposed to any stimulants, the experimental group was treated with LPS, TNF-α, or UVB, and another group was treated again with calcipotriol; reverse transcriptase-polymerase chain reaction, Western blotting, and immunohistochemical staining were performed. Results. In the experimental group treated with LPS, UVB irradiation, and TNF-α, the expression of β-defensin and LL-37 was increased more than in the control group and then decreased in the experimental group treated with calcipotriol. Conclusions. Calcipotriol suppressed HBD-2 and LL-37, which were stimulated by UVB, LPS, and TNF-α

Trichosanthes kirilowii

Trichosanthes kirilowii tuber is a traditional medicine which exhibits various medicinal effects including antidiabetic and anticancer activities in several cancer cells. Recently, it was reported that Cucurbitacin D (CuD) isolated from Trichosanthes kirilowii also induces apoptosis in several cancer cells. Constitutive signal transducer and activator of transcription 3 (STAT3), which is an oncogenic transcription factor, is often observed in many human malignant tumor, including breast cancer. In the present study, we tested whether Trichosanthes kirilowii ethanol extract (TKE) or CuD suppresses cell growth and induces apoptosis through inhibition of STAT3 activity in breast cancer cells. We found that both TKE and CuD suppressed proliferation and induced apoptosis and G2/M cell cycle arrest in MDA-MB-231 breast cancer cells by inhibiting STAT3 phosphorylation. In addition, both TKE and CuD inhibited nuclear translocation and transcriptional activity of STAT3. Taken together, our results indicate that TKE and its derived compound, CuD, could be potent therapeutic agents for breast cancer, blocking tumor cell proliferation and inducing apoptosis through suppression of STAT3 activity

Insulin-inducible SMILE inhibits hepatic gluconeogenesis

The role of a glucagon/cAMP-dependent protein kinase–inducible coactivator PGC-1α signaling pathway is well characterized in hepatic gluconeogenesis. However, an opposing protein kinase B (PKB)/Akt-inducible corepressor signaling pathway is unknown. A previous report has demonstrated that small heterodimer partner–interacting leucine zipper protein (SMILE) regulates the nuclear receptors and transcriptional factors that control hepatic gluconeogenesis. Here, we show that hepatic SMILE expression was induced by feeding in normal mice but not in db/db and high-fat diet (HFD)-fed mice. Interestingly, SMILE expression was induced by insulin in mouse primary hepatocyte and liver. Hepatic SMILE expression was not altered by refeeding in liver-specific insulin receptor knockout (LIRKO) or PKB β-deficient (PKBβ−/−) mice. At the molecular level, SMILE inhibited hepatocyte nuclear factor 4–mediated transcriptional activity via direct competition with PGC-1α. Moreover, ablation of SMILE augmented gluconeogenesis and increased blood glucose levels in mice. Conversely, overexpression of SMILE reduced hepatic gluconeogenic gene expression and ameliorated hyperglycemia and glucose intolerance in db/db and HFD-fed mice. Therefore, SMILE is an insulin-inducible corepressor that suppresses hepatic gluconeogenesis. Small molecules that enhance SMILE expression would have potential for treating hyperglycemia in diabetes

Genotype and Phenotype Spectrum of FRMD7-Associated Infantile Nystagmus Syndrome

PURPOSE. We investigate the genotype and phenotype spectrum of FRMD7-associated infantile nystagmus syndrome in Korean probands. METHODS. A total of 37 patients with infantile nystagmus syndrome were recruited prospectively for genetic analysis. We performed polymerase chain reaction (PCR)-based direct sequencing and haplotype analysis for FRMD7. Detailed ophthalmic examinations and eye movement recordings were compared between FRMD7 and non-FRMD7 groups. RESULTS. In 13 (35%) of 37 patients, five different mutations of FRMD7 were detected: start codon mutation c.1A>G, splice site mutation c.162thorn6T>C, and three missense mutations (c.575A>C, c.722A>G, and c.875T>C). The latter mutation was identified in seven unrelated patients, and always was accompanied with two single nucleotide polymorphisms of exon 12 (rs6637934, rs5977623). Compared to non-FRMD7 groups, a cup-to-disc ratio was significantly decreased in FRMD7 groups (P < 0.001), and a disc-macula distance to disc diameter ratio markedly increased in the FRMD7 group (P = 0.015). Most patients in the FRMD7 group had at least two types of the nystagmus waveforms, and the most common type was unidirectional jerk nystagmus (75%), such as pure jerk and jerk with extended foveation, followed by pendular (25%), bidirectional jerk (19%), and dual jerk (6%) nystagmus. No significant differences were observed between FRMD7 and non-FRMD7 groups in terms of the nystagmus waveform, presence of periodic alternating nystagmus, and mean foveation time. CONCLUSIONS. We identified five FRMD7 mutations in 35% of our infantile nystagmus syndrome cohort, expanding its mutational spectrum. The missense mutation c.875T>C may be a common mutation arisen from the founder effect in Korea. Optic nerve dysplasia associated with FRMD7 mutations suggests that the abnormal development of afferent visual systems may affect neural circuitry within the oculomotor syste

Calcified Carcinoma of the Gallbladder with Calcified Nodal Metastasis Presenting as a Porcelain Gallbladder: A Case Report

Porcelain gallbladder is regarded as a risk factor of gallbladder cancer. A porcelain gallbladder with calcified regional lymph nodes was found using computed tomography (CT) and magnetic resonance imaging (MRI) in a 43-year-old man who presented with nausea, vomiting, and abdominal pain. His cholecystectomy specimen showed diffuse wall thickening and contained small gallstones. Histological examination revealed diffuse infiltrative adenocarcinoma with extensive intratumoral calcification (calcified carcinoma). The majority of the calcified material was located within or replaced the tumor glands, and was not found in the stroma. A lymph node was totally replaced with a calcified metastatic adenocarcinoma. To the best of our knowledge, only one case of calcified lymph node metastasis from a calcified carcinoma of the gallbladder has been previously reported in the literature. We herein add a case of calcified carcinoma of the gallbladder with calcified lymph node metastasis, presenting as a porcelain gallbladder on CT and MRI

Chaperone-like protein DAY plays critical roles in photomorphogenesis.

Photomorphogenesis, light-mediated development, is an essential feature of all terrestrial plants. While chloroplast development and brassinosteroid (BR) signaling are known players in photomorphogenesis, proteins that regulate both pathways have yet to be identified. Here we report that DE-ETIOLATION IN THE DARK AND YELLOWING IN THE LIGHT (DAY), a membrane protein containing DnaJ-like domain, plays a dual-role in photomorphogenesis by stabilizing the BR receptor, BRI1, as well as a key enzyme in chlorophyll biosynthesis, POR. DAY localizes to both the endomembrane and chloroplasts via its first transmembrane domain and chloroplast transit peptide, respectively, and interacts with BRI1 and POR in their respective subcellular compartments. Using genetic analysis, we show that DAY acts independently on BR signaling and chlorophyll biogenesis. Collectively, this work uncovers DAY as a factor that simultaneously regulates BR signaling and chloroplast development, revealing a key regulator of photomorphogenesis that acts across cell compartments