Protective Effect of Bojungikki-Tang against Radiation-Induced Intestinal Injury in Mice: Experimental Verification and Compound-Target Prediction.

Bojungikki-tang (BJIT) is a traditional herbal medicine used in Korea, Japan, and China to treat gastrointestinal disorders. In this study, we aimed to investigate whether BJIT has protective effects against radiation-induced intestinal injury and to predict the underlying therapeutic mechanisms and related pathways via network pharmacological analyses. BJIT was injected intraperitoneally (50 mg/kg body weight) to C3H/HeN mice at 36 and 12 h before exposure to partial abdominal irradiation (5 Gy and 13 Gy) to evaluate the apoptotic changes and the histological changes and variations in inflammatory cytokine mRNA levels in the jejunum, respectively. Through in silico network analysis, we predicted the mechanisms underlying BJIT-mediated regulation of radiation-induced intestinal injury. BJIT reduced the level of apoptosis in the jejunal crypts 12 h post 5-Gy irradiation. Histological assessment revealed intestinal morphological changes in irradiated mice 3.5 days post 13-Gy irradiation. Furthermore, BJIT decreased inflammatory cytokine levels following radiation exposure. Apoptosis, TNF, p53, VEGF, toll-like receptor, PPAR, PI3K-Akt, and MAPK signaling pathways, as well as inflammatory bowel disease (IBD), were found to be linked to the radioprotective effects of BJIT against intestinal injury. According to our results, BJIT exerted its potential protective effects by attenuating histopathological changes in jejunal crypts and suppressing inflammatory mediator levels. Therefore, BJIT is a potential therapeutic agent that can treat radiation-induced intestinal injury and its associated symptoms.

The PERCIVAL detector: first user experiments.

The PERCIVAL detector is a CMOS imager designed for the soft X-ray regime at photon sources. Although still in its final development phase, it has recently seen its first user experiments: ptychography at a free-electron laser, holographic imaging at a storage ring and preliminary tests on X-ray photon correlation spectroscopy. The detector performed remarkably well in terms of spatial resolution achievable in the sample plane, owing to its small pixel size, large active area and very large dynamic range; but also in terms of its frame rate, which is significantly faster than traditional CCDs. In particular, it is the combination of these features which makes PERCIVAL an attractive option for soft X-ray science.

Molecular expression and functional features of Kv7 channels in human prostate smooth muscle.

BACKGROUND: Relaxation of prostate smooth muscle tone is a key strategy for the medical treatment of lower urinary tract symptoms (LUTS) in men. However, potassium channel's physiological role inhuman prostatic smooth muscle (HPrSM) has yet to be determined. OBJECTIVES: In this study, we examined the molecular characteristics and physiological roles of Kv7 channels in HPrSM. MATERIALS AND METHODS: The expressions of KCNQ1-5 (Kv7 channel pore-forming α-subunits) and KCNE1-5 (ß-regulatory subunits) isoforms in HPrSM were examined using real-time PCR. The relaxation effect of ML213 was investigated by cumulatively adding ML213 to the prostate strips. Kv7 currents were recorded using an amphotericin-B perforated patch-clamp technique. RESULTS: In HPrSM cells, KCNQ4, KCNQ5, and KCNE4 isoforms were predominantly expressed, while KCNQ1, KCNQ5, and KCNE3 isoforms were the most abundantly expressed in human prostatic tissues. Western blot analysis revealed the protein expression of the Kv7.1, 7.4, and 7.5 channel subtypes in human prostate tissues (n = 3). ML213 (an activator of Kv7.2/7.4/7.5) induced the concentration-dependent relaxation of HPrSM strips (n = 15, p = 0.001), and this effect was attenuated by pretreatment with XE991 (a Kv7.1-7.5 blocker). In electrophysiology studies, ML213 significantly increased the amplitude of whole-cell Kv7 currents in HPrSM cells. ML213-induced outward currents were greater than retigabine (a Kv7.2-7.5 channel activator). The subsequent addition of XE991 completely inhibited the ML213-induced currents (n = 9, p < 0.01 vs. ML213). ML213 hyperpolarized the HPrSM cell membrane potential and was fully reversed by XE991. In situ PLA revealed the colocalization of heteromeric KV7.4/KV7.5 channels in HPrSM cells. CONCLUSIONS: Our findings suggest that Kv7.4 and 7.5 channels in prostatic smooth muscle play a critical role in the regulation of HPrSM tone and that Kv7 channel subtypes may be novel therapeutic targets for the treatment of LUTS associated with BPH.

Subnanosecond phase transition dynamics in laser-shocked iron.

Iron is one of the most studied chemical elements due to its sociotechnological and planetary importance; hence, understanding its structural transition dynamics is of vital interest. By combining a short pulse optical laser and an ultrashort free electron laser pulse, we have observed the subnanosecond structural dynamics of iron from high-quality x-ray diffraction data measured at 50-ps intervals up to 2500 ps. We unequivocally identify a three-wave structure during the initial compression and a two-wave structure during the decaying shock, involving all of the known structural types of iron (α-, γ-, and ε-phase). In the final stage, negative lattice pressures are generated by the propagation of rarefaction waves, leading to the formation of expanded phases and the recovery of γ-phase. Our observations demonstrate the unique capability of measuring the atomistic evolution during the entire lattice compression and release processes at unprecedented time and strain rate.

Dissipation, persistence, and risk assessment of fluxapyroxad and penthiopyrad residues in perilla leaf (Perilla frutescens var. japonica Hara).

The objective of this study was to determine the residual characteristics and to calculate the persistence of the fungicides fluxapyroxad (15.3% suspension concentrate) and penthiopyrad (20% emulsifiable concentrate) on the leaves of greenhouse-cultivated perilla (Perilla frutescens var. japonica Hara). Fluxapyroxad was diluted 2,000-fold and penthiopyrad was diluted 4,000-fold. Each solution was sprayed 3 times onto crops at 7-d intervals before harvest. Leaf samples were collected at 3 h (0 d), 1, 3, 5 and 7 d after the third and final treatment. The recovery ranges of fluxapyroxad and penthiopyrad and their metabolites were 74.2%-104.1%. Pesticide residue analyses indicated that fluxapyroxad and penthiopyrad residues in perilla leaves dissipated over time. The persistence of fluxapyroxad and penthiopyrad residues 7 d after the final spray were 50.0% ± 4.9% and 44.2% ± 2.8% of those measured 3 h (0 d) after the final spray, respectively. The percent acceptable daily intake (%ADI)-which was assessed according to the daily food intake by Koreans according to age-was < 7.3%. Therefore, it was determined that the health risk was low. The perception that residual pesticides are present in large amounts in perilla leaf has led to consumer concern. However, in this study, the amounts of pesticide in perilla leaf decreased over time. Although it has been hypothesized that the risk of pesticide intake would be higher in younger children, the results actually suggest the opposite. Therefore, the pesticides in question are considered to be safe for use on perilla leaves.

Impact of pediatric cardiac surgery regionalization on health care utilization and mortality.

OBJECTIVE: Regionalization directs patients to high-volume hospitals for specialized care. We investigated regionalization trends and outcomes in pediatric cardiac surgery. DATA SOURCES/STUDY SETTING: Statewide inpatient data from eleven states between 2000 and 2012. STUDY DESIGN: Mortality, length of stay (LOS), and cost were assessed using multivariable hierarchical regression with state and year fixed effects. Primary predictor was hospital case-volume, categorized into low-, medium-, and high-volume tertiles. DATA COLLECTION/EXTRACTION METHODS: We used Risk Adjustment for Congenital Heart Surgery-1 (RACHS-1) to select pediatric cardiac surgery discharges. PRINCIPAL FINDINGS: In total, 2841 (8.5 percent), 8348 (25.1 percent), and 22 099 (66.4 percent) patients underwent heart surgeries in low-, medium-, and high-volume hospitals. Mortality decreased over time, but remained higher in low- and medium-volume hospitals. High-volume hospitals had lower odds of mortality and cost than low-volume hospitals (odds ratio [OR] 0.59, P < 0.01, and relative risk [RR] 0.91, P < 0.01, respectively). LOS was longer for high- and medium-volume hospitals, compared to low-volume hospitals (high-volume: RR 1.18, P < 0.01; medium-volume: RR 1.05, P < 0.01). CONCLUSIONS: Regionalization reduced mortality and cost, indicating fewer complications, but paradoxically increased LOS. Further research is needed to explore the full impact on health care utilization.

Crystal structure of the apo form of a ß-transaminase from Mesorhizobium sp. strain LUK.

Pyridoxal 5'-phosphate (PLP)-dependent ß-transaminases (ßTAs) reversibly catalyze transamination reactions by recognizing amino groups linked to the ß-carbon atoms of their substrates. Although several ßTA structures have been determined as holo forms containing PLP, little is known about the effect of PLP on the conversion of the apo structure to the holo structure. We determined the crystal structure of the apo form of a ßTA from Mesorhizobium sp. strain LUK at 2.2 Å resolution to elucidate how PLP affects the ßTA structure. The structure revealed three major disordered regions near the active site. Structural comparison with the holo form also showed that the disordered regions in the apo form are ordered and partially adopt secondary structures in the holo form. These findings suggest that PLP incorporation into the active site contributes to the structural stability of the active site architecture, thereby forming the complete active site. Our results provide novel structural insights into the role of PLP in terms of active site formation.

High-Frequency Ultrasound Imaging for Examination of Early Dental Caries.

The extent of dental tissue destruction during the treatment of white spot lesions (WSLs) increases with the severity of the lesion. If the depth and shape of WSLs can be predicted with a noninvasive diagnostic method before dental caries treatment, more conservative interventions can be planned. Given the superiority of high-frequency ultrasound (HFUS) imaging in observing the internal structures of the body, the present study aimed to verify the possibility of HFUS imaging to examine the depth and shape of WSLs. We prepared tooth samples and developed a biomicroscopic system with a HFUS transducer to obtain images of normal and WSL regions. HFUS images were compared with conventional ultrasound images and micro-computed tomography images. HFUS distinctly differentiated demineralization within WSL and normal regions. WSL depth calculated in the micro-computed tomography image was similar to that in HFUS. This study revealed that HFUS imaging has the potential to detect early dental caries and offer information on the invasion depth of early dental caries quantitatively.

Risk of dermal and inhalation exposure to chlorantraniliprole assessed by using whole-body dosimetry in Korea.

BACKGROUND: We determined the characteristics and evaluated associated risks of sprayed pesticide exposure among workers cultivating Korean cabbage. The test pesticide, a mixture of 3% chlorantraniliprole and 4% indoxacarb wettable granules diluted 2000 times, was sprayed on Korean cabbage within a 3000 m2 area in Goesan, Korea. Dermal exposures were measured using a whole-body dosimetry method. RESULTS: Exposure to chlorantraniliprole was observed among ten individuals, ranging from 140.4 to 4234.0 µg person-1 . The legs were the most prominent exposure area (86.35%), with the face being the least exposed (0.06%). Exposure risk was assessed by calculating the margin of safety (MOS) on the exposure amount for each body part. The MOS based on dermal and inhalation exposure doses ranged from 59 to 1765. CONCLUSION: Exposure was the greatest for the legs, probably as a result of the low height of the crop and the use of a long-wand sprayer. An MOS value >1 indicates a low risk for applicators using this method of application. However, with tall crops, exposure level and MOS values can vary widely, as MOS increases or decreases based on exposure dose. Therefore, future research is needed to better understand appropriate safety precautions when working with potent pesticides. © 2018 Society of Chemical Industry.

Structure of TRAF Family: Current Understanding of Receptor Recognition.

Tumor necrosis factor receptor-associated factor (TRAF) proteins are key signaling molecules that function in various cellular signaling events including immune response, cell death and survival, development, and thrombosis. Their roles in cellular signaling are mediated mostly by direct interactions with various receptors via the TRAF domain. To determine how specific TRAF domains can interact with various receptors with a limited binding interface and how similar binding interfaces of TRAF family members can recognize their specific binding partners, extensive structural studies on TRAF family proteins have been conducted for several decades. In this review, we discuss the current understanding of the structural and molecular diversity of the TRAF domain and TRAF-binding motifs in many receptors according to available structural information.

Hypoplastic AI with Highly Variable Expressivity Caused by ENAM Mutations.

Tooth enamel, the hardest tissue in the human body, is formed after a complex series of interactions between dental epithelial tissue and the underlying ectomesenchyme. Nonsyndromic amelogenesis imperfecta (AI) is a rare genetic disorder affecting tooth enamel without other nonoral symptoms. In this study, we identified 2 novel ENAM mutations in 2 families with hypoplastic AI by whole exome sequencing. Family 1 had a heterozygous splicing donor site mutation in intron 4, NM_031889; c.123+2T>G. Affected individuals had hypoplastic enamel with or without the characteristic horizontal hypoplastic grooves in some teeth. Family 2 had a nonsense mutation in the last exon, c.1842C>G, p.(Tyr614*), that was predicted to truncate the protein by 500 amino acids. Participating individuals had at least 1 mutant allele, while the proband had a homozygous mutation. Most interestingly, the clinical phenotype of the individuals harboring the heterozygous mutation varied from a lack of penetrance to a mild hypoplastic enamel defect. We believe that these findings will broaden our understanding of the clinical phenotype of AI caused by ENAM mutations.

Dental implications in Hajdu-Cheney syndrome: A novel case report and review of the literature.

OBJECTIVE: To identify the molecular genetic etiology of an individual with a dysmorphic face, unusual teeth mobility, and root resorption. SUBJECTS AND METHODS: DNA samples were collected from a trio of family members, and whole-exome sequencing was performed. RESULTS: Mutational analysis revealed a de novo mutation (c.6787C>T) in the last exon of the NOTCH2 gene. This mutation would introduce a premature stop codon [p.(Gln2263*)] and generate a truncated protein without C-terminus, escaping from the nonsense-mediated decay system. Sanger sequencing confirmed that this mutation was generated spontaneously. CONCLUSIONS: In this study, we identified a novel nonsense mutation in the last exon of the NOTCH2 gene causing Hajdu-Cheney syndrome. We described the genotype and phenotype correlation and the related dental complications. These results will advance the understanding of the NOTCH2 signaling in periodontitis and root resorption.

Frequency and risk factors of colorectal adenoma in patients with early gastric cancer.

BACKGROUND/AIM: The authors aimed to determine the clinical value of colonoscopy by evaluating the frequency of colorectal neoplasm (CRN) detection in patients with early gastric cancer (EGC) as compared with healthy controls and analysed the risk factors of advanced CRN in patients with EGC. METHODS: The medical records of 201 patients diagnosed as EGC and age- and gender-matched healthy controls were retrospectively reviewed. Frequencies and clinical features of colorectal polyps of patients and controls were compared. Risk factors of advanced CRN in patients with EGC were also analysed. RESULTS: Frequencies of CRN in patients and controls were 49.8 and 49.3% respectively (P = 0.90). They were more common in the right colon in patients (P < 0.05). Advanced CRN were found in 10.3% of patients and in 3% of controls (P < 0.05). Multivariate analysis revealed that old age and smoking history were risk factors of an advanced CRN in patients with EGC. CONCLUSION: The prevalence of a coexisting advanced CRN was higher in EGC patients. The study shows colonoscopy plays an important role with respect to the detection of synchronous advanced CRN in patients with EGC.

Dental and skeletal maturation in female adolescents with temporomandibular joint osteoarthritis.

Occurrence of temporomandibular disorders (TMDs) and temporomandibular joint (TMJ) osteoarthritis (OA) during adolescence may have interactions with mandibular and dental development. The aim of the present study was to investigate relationships between occurrence of TMD and TMJ OA and extents of dental and skeletal development in juvenile female patients. In total, 95 female adolescents (age range, 11-15 years) were selected. Among them, 15 subjects (control) had no signs of TMD, 39 TMD patients did not have OA (TMDnoOA), 17 TMD patients were at initial stage of TMJ OA (TMJOA), and 27 patients showed progressive stage of TMJ OA (TMJOA). Dental age was estimated by Demirjian's stages used in a previous study with Korean adolescents. Craniofacial parameters and cervical vertebrae maturation (CVM) stages, representing skeletal maturity levels, were measured using lateral cephalograms. The estimated dental age was significantly lower than chronological age in all groups, but CVM differences were not statistically significant. Dental age was the lowest, and differences between the chronological age and estimated dental age were the highest among initial stage of TMJOAs followed by progressive stage of TMJOAs, TMDnoOAs and control and were not associated with CVM stages. Cephalometric parameters revealed significant clockwise rotation of the mandible among the TMJOAs compared with controls and TMDnoOAs and were not associated with CVM stages as well. The juvenile female patients with TMD, particularly TMJ OA, showed retarded dental development, mandibular backward positioning and hyperdivergent facial profiles. The TMJ OA may be associated with retarded dental development but not with skeletal maturations.

Peri-vulvar reconstruction using internal pudendal artery perforator flap in female Fournier's gangrene.

Fournier's gangrene in female patients has low incidence rate but high mortality rate compared with that in males, with many cases resulting in death at acute phase. This is due to the differences in male and female genital anatomy, which should be fully understood by physicians to increase the patient's survival rate. After crossing the acute phase of the disease by an appropriate treatment, it is important to reconstruct vaginal or vulvar defects according to the patient's three-dimensional anatomical structures. Perforator flap based on internal pudendal artery is one of the ideal reconstructive techniques to resolve the aforementioned issue. The authors intend to introduce the distinguishing characteristics of Fournier's gangrene in female patients, and the surgical techniques to reconstruct the defects after the acute phase of disease.

Successful treatment of areolar Fox-Fordyce disease with surgical excision and 1550-nm fractionated erbium glass laser.

Fox-Fordyce disease (FFD) is a rare chronic disorder characterised by persistent inflammation because of the obstruction of apocrine sweat glands, which is a key factor of pathogenesis. The treatment of FFD is known to be difficult, and the modalities of treatment have not yet been widely studied. We report the successful treatment of a case of bilateral areolar FFD by a combination of surgical excision and 1550-nm fractionated erbium glass laser in an 18-year-old woman. The patient presented with a bilateral areolar eruption of multiple, severely pruritic, 3-4 mm skin- to grey-coloured folliculocentric dome-shaped papules. The initial treatment plan was for bilateral surgical excision of the larger and more highly elevated papules via circumferential dermal excision, which was intended to maintain the areolar contour and minimise distortion. A 1550-nm fractional erbium glass laser was then used to control the remnant lesions. The patient was recurrence-free at 14 months after the final laser treatment, and she was fully satisfied with the treatment results.

Unexpected identification of a recurrent mutation in the DLX3 gene causing amelogenesis imperfecta.

OBJECTIVE: To identify the molecular genetic aetiology of a family with autosomal dominant amelogenesis imperfecta (AI). SUBJECTS AND METHODS: DNA samples were collected from a six-generation family, and the candidate gene approach was used to screen for the enamelin (ENAM) gene. Whole-exome sequencing and linkage analysis with SNP array data identified linked regions, and candidate gene screening was performed. RESULTS: Mutational analysis revealed a mutation (c.561_562delCT and p.Tyr188Glnfs*13) in the DLX3 gene. After finding a recurrent DLX3 mutation, the clinical phenotype of the family members was re-examined. The proband's mother had pulp elongation in the third molars. The proband had not hair phenotype, but her cousin had curly hair at birth. CONCLUSIONS: In this study, we identified a recurrent 2-bp deletional DLX3 mutation in a new family. The clinical phenotype was the mildest one associated with the DLX3 mutations. These results will advance the understanding of the functional role of DLX3 in developmental processes.

Internal pudendal perforator artery-based gull wing flap for vulvovaginal 3D reconstruction after tumour excision: a new flap.

Various skin tumours such as squamous cell carcinoma and extramammary Paget's disease can occur in the vulval area, and reconstruction of the vulval area can be a very challenging task. A retrospective analysis of vulvar reconstruction using the new method 'internal pudendal perforator artery-based gull wing flap' was performed from April 2012 to December 2013. A perforator vessel from the internal pudendal artery was detected with a portable Doppler and marked, and this was the pivot point around which the flap was rotated. The flap was rotated by more than 150°-180° internally, and the labium and the external wall of the vagina were reconstructed with sufficient volume. Anatomical and aesthetic reconstruction of the labium and the vagina was performed without serious complications. Functional and aesthetic vulvar reconstruction can be achieved by using a flap that provides sufficient volume of the labium. Our new technique, the 'internal pudendal perforator artery-based gull wing flap', is good and it can be used to reconstruct a functional and aesthetically acceptable vulvovagina for large defect wound after tumour excision.

Scrotal reconstruction using a superficial circumflex iliac artery perforator flap following Fournier's gangrene.

Fournier's gangrene is a type of necrotising fasciitis around the scrotum and perineum. Because of its aggressive nature, patients should be treated with broad-spectrum antibiotics and emergency, radical debridement during the acute phase. After recovering from the acute phase, reconstruction of the scrotal and perineal soft tissue defects is needed and is often challenging. Traditionally, various reconstruction methods have been used, including skin grafts, fasciocutaneous flaps and musculocutaneous flaps, each with its pros and cons. We successfully covered a wide scrotal defect using a superficial circumflex iliac artery perforator flap, which has not been previously reported for this indication. The design and operative technique are introduced in this study.

Endoplasmic reticulum (ER) stress protein responses in relation to spatio-temporal dynamics of astroglial responses to status epilepticus in rats.

In the present study, we investigated whether endoplasmic reticulum (ER) stress is associated with neuronal- and astroglial-death in the hippocampus using LiCl-pilocarpine-induced status epilepticus (SE) rat model. Glucose-related protein (GRP) 78 and protein disulfide isomerase (PDI) expressions were transiently increased in CA1 neurons and dentate granule cells, and subsequently decreased in these cells following SE. GRP94 and calnexin (CNX) expression was gradually reduced in CA1 neurons, not in dentate granule cells. Phospho-protein kinase RNA (PKR)-like ER kinase (pPERK), phospho-eukaryotic initiation factor 2α (peIF2A) and CCAAT/enhancer-binding protein homologous protein (CHOP) immunoreactivities were observed in 17%, 12% and 7% of degenerating CA1 neurons, respectively. GRP 78 and PDI expressions were also up-regulated in reactive astrocytes within the CA1-3 regions. In the molecular layer of the dentate gyrus, PDI-positive astrocytes showed TUNEL signal, nuclear apoptosis inducing factor translocation and pPERK/peIF2A/CHOP immunoreactivities. Four weeks after SE, clasmatodendritic astrocytes showed pPERK peIF2A and CNX immunoreactivities without CHOP expression. These findings indicate that SE-induced ER stress may be associated with astroglial apoptosis and autophagic astroglial death in the regional-specific pattern.