Artificial Intelligence Model Assisting Thyroid Nodule Diagnosis and Management: A Multicenter Diagnostic Study.

CONTEXT: It is not clear how to integrate artificial intelligence (AI)-based models into diagnostic workflows. OBJECTIVE: To develop and validate a deep-learning-based AI model (AI-Thyroid) for thyroid cancer diagnosis, and to explore how this improves diagnostic performance. METHODS: The system was trained using 19 711 images of 6163 patients in a tertiary hospital (Ajou University Medical Center; AUMC). It was validated using 11 185 images of 4820 patients in 24 hospitals (test set 1) and 4490 images of 2367 patients in AUMC (test set 2). The clinical implications were determined by comparing the findings of six physicians with different levels of experience (group 1: 4 trainees, and group 2: 2 faculty radiologists) before and after AI-Thyroid assistance. RESULTS: The area under the receiver operating characteristic (AUROC) curve of AI-Thyroid was 0.939. The AUROC, sensitivity, and specificity were 0.922, 87.0%, and 81.5% for test set 1 and 0.938, 89.9%, and 81.6% for test set 2. The AUROCs of AI-Thyroid did not differ significantly according to the prevalence of malignancies (>15.0% vs ≤15.0%, P = .226). In the simulated scenario, AI-Thyroid assistance changed the AUROC, sensitivity, and specificity from 0.854 to 0.945, from 84.2% to 92.7%, and from 72.9% to 86.6% (all P < .001) in group 1, and from 0.914 to 0.939 (P = .022), from 78.6% to 85.5% (P = .053) and from 91.9% to 92.5% (P = .683) in group 2. The interobserver agreement improved from moderate to substantial in both groups. CONCLUSION: AI-Thyroid can improve diagnostic performance and interobserver agreement in thyroid cancer diagnosis, especially in less-experienced physicians.

Association between diet quality and untreated dental caries: results from the Korea National Health and Nutrition Examination Survey.

BACKGROUND/OBJECTIVES: Few studies have provided evidence of the association between diet quality and dental caries. This study aimed to examine the association between diet quality and untreated dental caries in a Korean representative population. SUBJECTS/METHODS: The study population included a sample of 13,815 participants, aged ≥ 19 from the Korea National Health and Nutrition Examination Survey during 2013-2015. The explanatory variable was diet quality and the outcome variable was untreated dental caries. Untreated dental caries were defined by the number of decayed teeth recorded according to the criteria established by the World Health Organization. Diet quality was defined by using the Korean Healthy Eating Index (KHEI) through the 24-h recall methods. We assessed the association between diet quality and untreated dental caries while adjusting for age, sex, education, income, smoking status, dental visits, toothbrushing frequencies, obesity, and diabetes mellitus. RESULTS: The mean overall KHEI scores in the untreated dental caries group were significantly lower than those in the group without untreated dental caries. Significant differences were observed in the untreated dental caries group based on the KHEI quartiles (P < 0.001). After adjusting for potential confounders, the quartiles of KHEI scores showed an association with untreated dental caries, demonstrating a dose-effect trend (odds ratio [OR], 1.57; 95% confidence interval [CI], 1.35-1.84 for 1st quartile; OR, 1.38; 95% CI, 1.19-1.59 for 2nd quartile; OR, 1.32; 95% CI, 1.14-1.53 for 3rd quartile; reference quartile highest]). CONCLUSIONS: The findings indicated an inverse association between diet quality and untreated dental caries in Korean adults. Healthcare providers should take into account the significant role of diet quality in preventing and managing oral health.

Contrast-enhanced CT-based Radiomics for the Differentiation of Anaplastic or Poorly Differentiated Thyroid Carcinoma from Differentiated Thyroid Carcinoma: A Pilot Study.

Differential diagnosis of anaplastic thyroid carcinoma/poorly differentiated thyroid carcinoma (ATC/PDTC) from differentiated thyroid carcinoma (DTC) is crucial in patients with large thyroid malignancies. This study creates a predictive model using radiomics feature analysis to differentiate ATC/PDTC from DTC. We compared the clinicoradiological characteristics and radiomics features extracted from a volume of interest on contrast-enhanced computed tomography (CT) between the groups. Estimations of variable importance were performed via modeling using the random forest quantile classifier. The diagnostic performance of the model with radiomics features alone had the area under the receiver operating characteristic (AUROC) curve value of 0.883. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were 81.7%, 93.3%, 97.7%, 64.5%, and 84.6%, respectively, for the differential diagnosis of ATC/PDTC and DTC. The model with both radiomics and clinicoradiological information showed the AUROC of 0.908, with sensitivity, specificity, PPV, NPV, and accuracy of 82.9%, 97.6%, 99.2%, 67.1%, and 86.5% respectively. Distant metastasis, moment, shape, age, and gray-level size zone matrix features were the most useful factors for differential diagnosis. Therefore, we concluded that a radiomics approach based on contrast-enhanced CT features can potentially differentiate ATC/PDTC from DTC in patients with large thyroid malignancies.

Establishment of muscle mass-based indications for the cystatin C test in renal function evaluation.

Background: We aimed to suggest muscle mass-based criteria for using of the cystatin C test for the accurate estimated glomerular filtration rate (eGFR). Materials and methods: We recruited 138 Korean subjects and evaluated eGFRcr (derived from Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) based on creatinine) was compared to eGFRcys based on cystatin C as the reference value. The skeletal muscle mass index (SMI) by bioelectrical impedance analysis (BIA) was used as representative of muscle mass. Calf circumference (CC) was also evaluated. We defined the patients by eGFRcr as those with values of eGFRcr ≥ 60 mL/min/1.73 m2 but eGFRcys < 60 mL/min/1.73 m2 as the detection of hidden renal impairment (DHRI). Cut-off values were determined based on muscle mass for the cases of DHRI suggesting the criteria of cystatin C test in renal function evaluation. Results: We confirmed significant negative correlation between %difference of eGFRcr from eGFRcys and SMI (r, -0.592 for male, -0.484 for female) or CC (r, -0.646 for male, -0.351 for female). SMI of 7.3 kg/m2 for males and 5.7 kg/m2 for females were suggested to be significant cutoffs for indication of cystatin C test. We also suggested CC would be valuable for cystatin C indication. Conclusion: We suggested the muscle mass-based objective criteria relating to SMI and CC that would indicate the use of cystatin C to evaluate renal function test in sarcopenic cases. Our results highlight the importance of muscle mass-based selection of renal function.

Periodontal disease could be a potential risk factor for non-alcoholic fatty liver disease: An 11-year retrospective follow-up study.

OBJECTIVE: This study aimed to evaluate the association of periodontal disease with non-alcoholic fatty liver disease (NAFLD). MATERIALS AND METHODS: A retrospective follow-up study using the National Health Insurance Service-National Sample Cohort was performed from 2002 to 2015 in the Korean population. A total of 165,032 subjects were followed up for incident NAFLD during 11 years. Periodontal disease and NAFLD were defined by a diagnosis using the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10) codes. Periodontal status was used as the severity of periodontal status and the number of dental visit due to PD. RESULTS: Periodontitis was associated with a 4% increase in risk for NAFLD after adjusting for socio-demographic factor, health behaviors, and systemic diseases (adjusted hazard ratio [aHR] = 1.04, 95% CI = 1.01 to 1.07). Between the number of dental visit due to PD and the risk for NAFLD was observed a dose-effect association (aHR = 1.02, 95% CI = 0.99 to 1.05 for once; aHR = 1.10, 95% CI = 1.06 to 1.15 for two times; aHR = 1.14, 95% CI = 1.06 to 1.24 for three times). CONCLUSIONS: Our data confirmed that periodontitis showed an association with a higher incidence of NAFLD. CLINICAL RELEVANCE: Prevention and management of periodontal disease could be beneficial for reducing the risk of NAFLD.

Ciliated muconodular papillary tumor of the lung with cavitary change: A case report with 11-year preoperative follow-up.

Ciliated muconodular papillary tumor (CMPT) is a rare benign lung tumor characterized by ciliated columnar cells, mucous cells, and basal cells. Herein, we report a case of CMPT with 11 years of preoperative follow-up, depicting the natural course of the tumor and changes in computed tomography (CT) findings. A 39-year-old man had a 5-mm solid pulmonary nodule in the right lower lobe that had slowly grown and transformed into a thin-walled cavitary lesion. Right lower lobe lobectomy was performed and the tumor was confirmed to be a CMPT. Although it is difficult to diagnose CMPT with CT findings alone, CMPT should be considered as a possible diagnosis when a slowly growing nodule undergoes cavitary changes.

Technical feasibility and efficacy of a standard needle magnetization system for ultrasound needle guidance in thyroid nodule-targeting punctures: a phantom study.

PURPOSE: The aim of this study was to assess the feasibility and efficacy of an ultrasound needle guidance system (NGS) based on standard needle magnetization in a phantom study of thyroid nodule (TN)-targeting punctures. METHODS: Six trainees and a staff radiologist performed TN-targeting punctures with or without the NGS in phantom models (group 1, experience <50 cases; group 2, experience ≥50 cases and <100 cases; group 3, experience ≥100 cases of TN-targeting punctures). The feasibility, technical success rate, number of punctures, and procedure time were recorded. RESULTS: The feasibility of NGS was 98.6% (138/140). In group 1, the technical success rate increased from 60.0%±8.2% to 80.0%±8.2% when the NGS was used (P=0.046), with a reduction in the number of punctures from 2.2 to 1.2 (P=0.005). In group 2, the rate changed from 95.0%±5.8% to 100.0%±0.0% with the NGS (P=0.157), with a minimal decrease in the number of punctures from 1.1 to 1.0 (P=0.157). The procedure time significantly decreased in both groups (P=0.041 and P=0.010, respectively) when the NGS was used. In group 3, there were no significant differences in the technical success rate and the number of punctures according to whether the NGS was used (P=0.317 and P=0.317, respectively). CONCLUSION: NGS using standard needle magnetization is technically feasible and has potential to improve the efficacy of TN-targeting punctures for less-experienced operators, especially beginners, according to the findings of this phantom study.

Protective efficacy of the recombinant lysozyme-PMAP36 fusion protein-inactivated Salmonella Typhimurium vaccine candidate via oral immunization in a murine model.

The aim of this study was to evaluate protective efficacy of S. Typhimurium ghost vaccine candidate lysed by the recombinant lysozyme-PMAP36 fusion protein via oral immunization in a murine model. Sixty BALB/c mice were equally divided into 4 groups. Group A mice were inoculated with 20 µL of sterile phosphate-buffered saline (PBS). Groups B-D mice were immunized with approximately 1 × 107, 1 × 108, and 1 × 109 cells of the vaccine candidate, respectively, in 20 µL of PBS. Salmonella-outermembrane-proteins-specific serum IgG was considerably higher in groups B-D than in group A. The interleukin-10 and interferon-γ levels in groups B-D were significantly higher than in group A. Following challenge with wild-type S. Typhimurium, all immunized groups showed a significant level of protection compared with group A. The highest protection was shown in group D. Overall, these results show that oral immunization with the candidate vaccine can effectively protect mice from S. Typhimurium infection.

L'objectif de la présente étude était d'évaluer l'efficacité protectrice d'un vaccin candidat préparé à partir de cellules fantômes de Salmonella Typhimurium lysés par la protéine de fusion recombinante lysozyme-PMAP36 via immunisation orale dans un modèle murin. Soixante souris BALB/c ont été réparties également en quatre groupes. Les souris du Groupe A furent inoculées avec 20 µL de saline tamponnée stérile (PBS). Les souris des groupes B-D furent immunisées avec approximativement 1 × 107, 1 × 108, et 1 × 109 cellules du vaccin candidat, respectivement, dans 20 µL de PBS. Les IgG sériques spécifiques aux protéines de la paroi externe de Salmonella étaient considérablement plus élevées dans les groupes B-D que dans le groupe A. Dans les groupes B-D les niveaux d'interleukine-10 et d'interféron-γ étaient significativement plus élevés que dans le groupe A. À la suite d'une infection-défi avec une souche sauvage de S. Typhimurium, tous les groupes immunisés ont présenté un degré de protection significatif comparativement au groupe A. La meilleure protection était retrouvée dans le groupe D. De manière globale, ces résultats montrent que l'immunisation orale avec le vaccin candidat peut effectivement protéger des souris contre une infection par S. Typhimurium.(Traduit par Docteur Serge Messier).

Development of a Reporter System Monitoring Regulated Intramembrane Proteolysis of the Transmembrane bZIP Transcription Factor ATF6α.

When endoplasmic reticulum (ER) functions are perturbed, the ER induces several signaling pathways called unfolded protein response to reestablish ER homeostasis through three ER transmembrane proteins: inositol-requiring enzyme 1 (IRE1), PKR-like ER kinase (PERK), and activating transcription factor 6 (ATF6). Although it is important to measure the activity of ATF6 that can indicate the status of the ER, no specific cell-based reporter assay is currently available. Here, we report a new cell-based method for monitoring ER stress based on the cleavage of ATF6α by sequential actions of proteases at the Golgi apparatus during ER stress. A new expressing vector was constructed by using fusion gene of GAL4 DNA binding domain (GAL4DBD) and activation domain derived from herpes simplex virus VP16 protein (VP16AD) followed by a human ATF6α N-terminal deletion variant. During ER stress, the GAL4DBD-VP16AD(GV)-hATF6α deletion variant was cleaved to liberate active transcription activator encompassing GV-hATF6α fragment which could translocate into the nucleus. The translocated GV-hATF6α fragment strongly induced the expression of firefly luciferase in HeLa Luciferase Reporter cell line containing a stably integrated 5X GAL4 site-luciferase gene. The established double stable reporter cell line HLR-GV-hATF6α(333) represents an innovative tool to investigate regulated intramembrane proteolysis of ATF6α. It can substitute active pATF6(N) binding motif-based reporter cell lines.

Protective efficacy of a Brucella vaccine using a Salmonella-based delivery system expressing Brucella Omp3b, BCSP31, and SOD proteins against brucellosis in Korean black goats.

This study aimed to assess the protective efficacy of a novel Brucella vaccine formulation in goats. Twenty black goats were separated into 2 groups. Group A was injected with 3.0 × 109 CFU (colony-forming units)/mL of a Salmonella-based delivery system harboring only vector (pMMP65). Group B was immunized with 3.0 × 109 CFU/mL of the vaccine, a mixture of 3 Brucella vaccine strains (using a Salmonella-based delivery system) expressing each recombinant B. abortus Omp3b, BCSP31, and SOD protein. No Salmonella delivery strain was isolated from all tested lymph nodes and parenchymal organs. Serum immunoglobulin (Ig) G titers and interferon gamma concentrations were significantly higher in group B than those in group A. After intraconjunctival challenge with virulent B. abortus strain 544, 40% of the vaccinated animals in group B were protected against B. abortus infection. The infection index and colonization of B. abortus in tested tissues was significantly lower in group B than group A. We conclude that this Brucella vaccine induces significant antigen-specific immune responses and provides effective protection against B. abortus infection in goats. Further studies are needed to enhance the protection rate of this Brucella vaccine and to discover its practical application in small ruminants.

La présente étude visait à évaluer l'efficacité protectrice d'une nouvelle formulation de vaccin contre Brucella chez les chèvres. Vingt chèvres noires furent séparées en deux groupes. Le Groupe A reçut par injection 3,0 × 109 unités formatrices de colonies (UFC)/mL de Salmonella servant de système de livraison ne contenant seulement que le vecteur (pMMP65). Le groupe B fut immunisé avec 3,0 × 109 UFC/mL du vaccin, un mélange de trois souches vaccinales de Brucella (utilisant le système de livraison à base de Salmonella) exprimant chaque protéine recombinante Omp3b, BCSP31, et SOD de B. abortus. Aucune bactérie Salmonella du système de livraison ne fut isolée des ganglions lymphatiques et organes testés. Les concentrations sériques d'immunoglobulines G (IgG) et d'interféron gamma étaient significativement plus élevées dans le groupe B que dans le groupe A. À la suite d'une infection défi par voie intra-conjonctivale avec une souche virulente de B. abortus (544), 40 % des animaux vaccinés dans le groupe B étaient protégés contre l'infection par B. abortus. L'index d'infection et de colonisation par B. abortus dans les tissus testés étaient significativement plus faible dans le groupe B comparativement au groupe A. Nous avons conclu que ce vaccin contre Brucella induisait des réponses immunes spécifiques d'antigène significatives et fournissait une protection efficace contre l'infection par B. abortus chez les chèvres. Des études additionnelles sont requises afin d'augmenter le taux de protection de ce vaccin (Brucella) et pour découvrir son application pratique chez les petits ruminants.(Traduit par Docteur Serge Messier).

Protective efficacy of an inactivated Brucella abortus vaccine candidate lysed by GI24 against brucellosis in Korean black goats.

The efficacy of GI24-lysed Brucella abortus cells as a vaccine candidate against brucellosis in goats was evaluated on 2 groups of Korean black goats. Group A goats were immunized subcutaneously (SC) with sterile phosphate-buffered saline, whereas group B goats were immunized SC with approximately 3 × 109 lysed B. abortus cells. Subcutaneous immunization with the lysed cells did not cause any negative impact on the overall clinical status, such as behavior and appetite, throughout the study period. The enzyme-linked immunosorbent assay (ELISA) optical densities values for B. abortus lipopolysaccharide in serum were considerably higher in group B than those in group A. Also, the levels of the cytokines interleukin 4 (IL-4), tumor necrosis factor-alpha (TNF-α), and interferon gamma (IFN-γ) were significantly elevated in group B compared with those in group A. Following intraconjunctival challenge with B. abortus strain 544, the severity of brucellosis in terms of infection index and colonization of B. abortus in tissues was significantly lower in group B than in group A. The present study concluded that 3 of 5 goats immunized with GI24-lysed bacteria were completely protected against challenge. Future investigations are required to improve the protective efficacy offered by lysed B. abortus cells for practical applications in small ruminants.

L'efficacité de cellules lysées de Brucella abortus GI24 comme vaccin candidat contre la brucellose chez les chèvres a été évaluée chez deux groupes de chèvres noires coréennes. Les chèvres du groupe A ont été immunisées par voie sous-cutanée (SC) avec de la saline tamponnée stérile, alors que les chèvres du groupe B ont été immunisées SC avec environ 3 × 109 cellules lysées de B. abortus. L'immunisation sous-cutanée avec les cellules lysées n'a pas eu d'impact négatif sur l'état clinique général, tel que le comportement et l'appétit, tout au long de la période d'étude. Les valeurs de densité optique obtenues lors d'épreuves immunoenzymatiques (ELISA) utilisant le lipopolysaccharide de B. abortus étaient considérablement plus élevées avec le sérum des animaux du groupe B que celui des animaux du groupe A. De plus, les niveaux des cytokines interleukine-4 (IL-4), du facteur-alpha nécrosant de tumeur (TNF-α), d'interféron-gamma (IFN-γ) étaient significativement plus élevés dans le groupe B comparativement au groupe A. Pour donner suite à l'infection-défi intra-conjonctivale avec la souche 544 de B. abortus, la sévérité de brucellose en termes d'index d'infection et de colonisation des tissus par B. abortus était significativement moindre dans le groupe B que dans le groupe A. La présente étude a permis de conclure que 3 des 5 chèvres immunisées avec les bactéries GI24 lysées étaient complètement protégées contre l'infection. Des études ultérieures sont requises pour améliorer l'efficacité protectrice offerte par les cellules lysées de B. abortus pour une application pratique chez les petits ruminants.(Traduit par Docteur Serge Messier).

Yb3+,Er3+,Eu3+-codoped YVO4 material for bioimaging with dual mode excitation.

We propose an efficient bioimaging strategy using Yb3+,Er3+,Eu3+-triplet doped YVO4 nanoparticles which were synthesized with polymer as a template. The obtained particles possess nanoscale, uniform, and flexible excitation. The effect of Eu3+ ions on the luminescence properties of YVO4:Yb3+,Er3+,Eu3+ was investigated. The upconversion mechanism of the prepared material was also discussed. The structure and optical properties of the prepared material were characterized by using X-ray diffraction (XRD), Fourier-transform IR spectroscopy (FTIR), scanning electron microscopy (SEM), Transmission electron microscopy (TEM) upconversion and photoluminescence spectra. The Commission International de I'Eclairage (CIE) chromaticity coordinates was investigated to confirm the performance of color luminescent emission. The prepared YVO4:Yb3+,Er3+,Eu3+ nanoparticles could be easily dispersed in water by surface modification with cysteine (Cys) and glutathione (GSH). The aqueous dispersion of the modified YVO4:Yb3+,Er3+,Eu3+ exhibits bright upconversion and downconversion luminescence and has been applied for bioimaging of HeLa cells. Our developed material with dual excitation offers a promising advance in bioimaging.

Deguelin Analogue SH-1242 Inhibits Hsp90 Activity and Exerts Potent Anticancer Efficacy with Limited Neurotoxicity.

The Hsp90 facilitates proper folding of signaling proteins associated with cancer progression, gaining attention as a target for therapeutic intervention. The natural rotenoid deguelin was identified as an Hsp90 inhibitor, but concerns about neurotoxicity have limited prospects for clinical development. In this study, we report progress on deguelin analogues that address this limitation, focusing on the novel analogue SH-1242 as a candidate to broadly target human lung cancer cells, including those that are chemoresistant or harboring KRAS mutations. In a KRAS-driven mouse model of lung cancer, SH-1242 administration reduced tumor multiplicity, volume, and load. Similarly, in human cell line-based or patient-derived tumor xenograft models, SH-1242 induced apoptosis and reduced tumor vasculature in the absence of detectable toxicity. In contrast to deguelin, SH-1242 toxicity was greatly reduced in normal cells and when administered to rats did not produce obvious histopathologic features in the brain. Mechanistic studies revealed that SH-1242 bound to the C-terminal ATP-binding pocket of Hsp90, disrupting the ability to interact with its co-chaperones and clients and triggering a degradation of client proteins without affecting Hsp70 expression. Taken together, our findings illustrate the superior properties of SH-1242 as an Hsp90 inhibitor and as an effective antitumor and minimally toxic agent, providing a foundation for advancing further preclinical and clinical studies.

Novel C6-substituted 1,3,4-oxadiazinones as potential anti-cancer agents.

The insulin-like growth factor 1 receptor (IGF-1R) is a membrane receptor tyrosine kinase over-expressed in a number of tumors. However, combating resistance is one of the main challenges in the currently available IGF-1R inhibitor-based cancer therapies. Increased Src activation has been reported to confer resistance to anti-IGF-1R therapeutics in various tumor cells. An urgent unmet need for IGF-1R inhibitors is to suppress Src rephosphorylation induced by current anti-IGF-1R regimens. In efforts to develop effective anticancer agents targeting the IGF-1R signaling pathway, we explored 2-aryl-1,3,4-oxadiazin-5-ones as a novel scaffold that is structurally unrelated to current tyrosine kinase inhibitors (TKIs). The compound, LL-2003, exhibited promising antitumor effects in vitro and in vivo; it effectively suppressed IGF-1R and Src and induced apoptosis in various non-small cell lung cancer cells. Further optimizations for enhanced potency in cellular assays need to be followed, but our strategy to identify novel IGF-1R/Src inhibitors may open a new avenue to develop more efficient anticancer agents.

A critical element of the light-induced quaternary structural changes in YtvA-LOV.

YtvA, a photosensory LOV (light-oxygen-voltage) protein from Bacillus subtilis, exists as a dimer that previously appeared to undergo surprisingly small structural changes after light illumination compared with other light-sensing proteins. However, we now report that light induces significant structural perturbations in a series of YtvA-LOV domain derivatives in which the Jα helix has been truncated or replaced. Results from native gel analysis showed significant mobility changes in these derivatives after light illumination; YtvA-LOV without the Jα helix dimerized in the dark state but existed as a monomer in the light state. The absence of the Jα helix also affected the dark regeneration kinetics and the stability of the flavin mononucleotide (FMN) binding to its binding site. Our results demonstrate an alternative way of photo-induced signal propagation that leads to a bigger functional response through dimer/monomer conversions of the YtvA-LOV than the local disruption of Jα helix in the As-LOV domain.

Light-regulated tetracycline binding to the Tet repressor.

Elucidation of the signal-transmission pathways between distant sites within proteins is of great importance in medical and bioengineering sciences. The use of optical methods to redesign protein functions is emerging as a general approach for the control of biological systems with high spatiotemporal precision. Here we report the detailed thermodynamic and kinetic characterization of novel chimeric light-regulated Tet repressor (TetR) switches in which light modulates the TetR function. Light absorbed by flavin mononucleotide (FMN) generates a signal that is transmitted to As-LOV and YtvA-LOV fused TetR proteins (LOV=light-oxygen-voltage), in which it alters the binding to tetracycline, the TetR ligand. The engineering of light-sensing protein modules with TetR is a valuable tool that deepens our understanding of the mechanism of signal transmission within proteins. In addition, the light-regulated changes of drug binding that we describe here suggest that engineered light-sensitive proteins may be used for the development of novel therapeutic strategies.

Effects of tetramethylpyrazine on microglia activation in spinal cord compression injury of mice.

Secondary mechanisms, including inflammation and microglia activation, serve as targets for the development and application of pharmacological strategies in the management of spinal cord injury (SCI). Tetramethylpyrazine (TMP), an active ingredient of Ligusticum wallichii (chuanxiong), has shown anti-inflammatory and neuroprotective effects against SCI. However, it remains uncertain whether the inflammation-suppressive effects of TMP play a modulatory role over microglia activation in SCI. The present study investigated the effects of TMP on microglia activation and pro-inflammatory cytokines in spinal cord compression injury in mice. For a real-time PCR measurement of pro-inflammatory cytokines, SCI was induced in mice by the clip compression method (30 g force, 1 min) and TMP (15 or 30 mg/kg, i.p.) was administered once, 30 minutes before the SCI induction. For immunohistochemistry, TMP (30 mg/kg, i.p.) treatment was given three times during the first 48 hours after the SCI. 30 mg/kg of TMP treatment reduced the up-regulation of TNF-α, IL-1ß and COX-2 mRNA in the spinal tissue at four hours after the SCI induction. TMP also significantly attenuated microglia activation and neutrophil infiltration at 48 hours after the SCI induction. In addition, iNOS expression in the spinal tissue was attenuated with TMP treatment. These results suggest that TMP plays a modulatory role in microglia activation and may protect the spinal cord from or potentially delay secondary spinal cord injury.

In vivo Investigation of Anti-diabetic Properties of Ripe Onion Juice in Normal and Streptozotocin-induced Diabetic Rats.

The acute and subacute hypoglycemic and antihyperglycemic effects of drinkable ripe onion juice (Commercial product name is "Black Onion Extract") were investigated in normal and streptozotocin-induced diabetic rats. For tests of acute and subacute hypoglycemic effects, ripe onion juice (5 and 15 mL/kg b.w.) was administered by oral gavage to normal Sprague Dawley rats and measurements of fasting glucose levels and oral glucose tolerance tests were performed. Tolbutamide was used as a reference drug at a single oral dose of 250 mg/kg b.w. To test anti-hyper-glycemic activity, the ripe onion juice was administered to streptozotocin-induced diabetic rats by oral gavage at single dose of 15 mL/kg b.w. per day for 7 consecutive days. Oral administration of the ripe onion juice at either dosed level of 5 or 15 mL/kg b.w. showed no remarkable acute hypoglycemic effect in normal rats. The two dosed levels caused a relatively small reduction, only 18% and 12% (5 and 15 mL/kg b.w., respectively) decrease in glucose levels at 2 h after glucose loading in normal rats. However, at 3 h after glucose loading, blood glucose levels in the ripe onion juice-dosed rats were decreased to the corresponding blood glucose level in tolbutamide-dosed rats. Although showing weak hypoglycemic potential compared to that of tolbutamide, oral administration of ripe onion juice (15 mL/kg b.w.) for a short period (8 days) resulted in a slight reduction in the blood glucose levels that had elevated in Streptozotocin-induced diabetic rats. In conclusion, these results suggest that the commercial product "Black Onion Extract" may possess anti-hyperglycemic potential in diabetes.

Surface mapping of motor points in biceps brachii muscle.

OBJECTIVE: To localize the site of motor points within human biceps brachii muscles through surface mapping using electrophysiological method. METHOD: We recorded the compound muscle action potentials of each lattice of the biceps brachii in 40 healthy subjects. Standardized reference lines were made as the following: 1) a horizontal reference line (elbow crease) and 2) a vertical reference line connecting coracoid process and mid-point of the horizontal reference line. The Compound muscle action potentials were mapped in reference to the standardized reference lines. The locations of motor points were mapped to the skin surface, in the ratio to the length of the vertical and the half of the horizontal reference lines. RESULTS: The motor point of the short head of biceps was located at 69.0±4.9% distal and 19.1±9.5% medial to the mid-point of horizontal reference line. The location of the motor point of the long head of the biceps was 67.3±4.3% distal and 21.4±8.7% lateral. The motor point of the short head of the biceps was located more medially and distally in the male subjects compared to that in the female (p<0.05). CONCLUSION: This study showed electrophysiological motor points of the biceps brachii muscles through surface mapping. This data might improve the clinical efficacy and the feasibility of motor point targeting, when injecting botulinum neurotoxin in biceps brachii.

An efficient method for the expression and reconstitution of thermostable Mn/Fe superoxide dismutase from Aeropyrum pernix K1.

The gene APE0743 encoding the superoxide dismutase (ApSOD) of a hyperthermophilic archaeon Aeropyrum pernix K1 was cloned and over-expressed as a GST fusion protein at a high level in Escherichia coli. The expressed protein was simply purified by the process of glutathione affinity chromatography and thrombin treatment. The ApSOD was a homodimer of 25 kDa subunits and a cambialistic SOD which was active with either Fe(II) or Mn(II) as a cofactor. The ApSOD was highly stable against high temperature. This thermostable ApSOD is expected to be applicable as a useful biocatalyst for medicine and bio-industrial processes.