Production of Transgenic Cloned Miniature Pigs with Membrane-bound Human Fas Ligand (FasL) by Somatic Cell Nuclear Transfer

Cell-mediated xenograft rejection, including NK cells and CD8+ CTL, is a major obstacle in successful pig-to-human xenotransplantation. Human CD8+ CTL and NK cells display high cytotoxicity for pig cells, mediated at least in part by the Fas/FasL pathway. To prevent cell-mediated xenocytotoxicity, a membrane-bound form of human FasL (mFasL) was generated as an inhibitor for CTL and NK cell cytotoxicity that could not be cleaved by metalloproteinase to produce putative soluble FasL. We produced two healthy transgenic pigs harboring the mFasL gene via somatic cell nuclear transfer (SCNT). In a cytotoxicity assay using transgenic clonal cell lines and transgenic pig ear cells, the rate of CD8+ CTL-mediated cytotoxicity was significantly reduced in transgenic pig's ear cells compared with that in normal minipig fetal fibroblasts. Our data indicate that grafts of transgenic pigs expressing membrane-bound human FasL control the cellular immune response to xenografts, creating a window of opportunity to facilitate xenograft survival

Effect of coating with combined chitosan and gallic acid on shelf-life stability of Jeju black cattle beef

Objective Beef of Jeju black cattle (JBC) is considered as a healthy meat type due to its significantly higher unsaturated fatty acids (UFA). Lipid (e.g., UFA) is highly susceptible to oxidizing agents, which results in the quality deterioration and economic value loss of meat products. Therefore, development and application of novel preservative techniques is necessary to improve the shelf-life stability of high-UFA beef. The objective of this study was to assess the applicability of chitosan-based coatings in preservation of JBC beef. Methods Different coating solutions: 2% chitosan alone, and 2% chitosan containing 0.1% or 0.3% gallic acid were prepared to investigate their applicability in preservation of fresh beef during storage. Jeju black cattle beef (2-cm thick steaks) were non-coated (control) or coated with the above coating solutions, placed on trays, over-wrapped with plastic film and stored at 4°C. The microbiological indices, color, total volatile basic nitrogen (TVBN) and lipid oxidation of the beef were investigated after 1, 10, and 21 days of storage. Results Coating with 2% chitosan alone reduced the spoilage bacteria count, TVBN and thiobarbituric acid reactive substances levels in the beef compared with control during storage (p<0.05). Noticeably, coating with 2% chitosan containing 0.1% or 0.3% gallic acid was more effective on retardation of spoilage bacteria growth, lipid oxidation and discoloration in the beef compared to the chitosan coating alone over the storage period (21 days) (p<0.05). Conclusion Taken together, the combined chitosan and gallic acid coating could be used as a bio-preservative technique in the meat industry

The Antidiabetic Drug Lobeglitazone Protects Mice From Lipogenesis-Induced Liver Injury via Mechanistic Target of Rapamycin Complex 1 Inhibition

Non-alcoholic fatty liver disease (NAFLD) is a metabolic disorder closely linked with type II diabetes (T2D). The progression of NAFLD is associated with the induction of lipogenesis through hyperactivation of the mechanistic target of rapamycin complex 1 (mTORC1) pathway. An increase in lipogenesis induces endoplasmic reticulum (ER) stress and accelerates oxidative liver injury in the pathogenesis of NAFLD. Lobeglitazone, one of thiazolidinediones (TZDs), is used as an antidiabetic drug to lower serum glucose level through an increase in insulin sensitivity. It is known to improve pathological symptoms in animals and humans with NAFLD. However, the underlying molecular mechanism of the protective effects of lobeglitazone against NAFLD has not been elucidated. Here, we show that under the physiological condition of acute lipogenesis, lobeglitazone inhibits hepatic lipid synthesis, the subsequent ER stress, and ω-oxidation of fatty acids by inhibiting the mTORC1 pathway. As a result, lobeglitazone protected mice from lipogenesis-induced oxidative liver injury. Taken together, lobeglitazone might be a suitable drug for the treatment of patients with diabetes and NAFLD

Usefulness of Impulse Oscillometry in Predicting the Severity of Bronchiectasis

Background Bronchiectasis is a chronic respiratory disease that leads to airway inflammation, destruction, and airflow limitation, which reflects its severity. Impulse oscillometry (IOS) is a non-invasive method that uses sound waves to estimate lung function and airway resistance. The aim of this study was to assess the usefulness of IOS in predicting the severity of bronchiectasis. Methods We retrospectively reviewed the IOS parameters and clinical characteristics in 145 patients diagnosed with bronchiectasis between March 2020 and May 2021. Disease severity was evaluated using the FACED score, and patients were divided into mild and moderate/severe groups. Results Forty-four patients (30.3%) were in the moderate/severe group, and 101 (69.7%) were in the mild group. Patients with moderate/severe bronchiectasis had a higher airway resistance at 5 Hz (R5), a higher difference between the resistance at 5 and 20 Hz (R5−R20), a higher resonant frequency (Fres), and a higher area of reactance (AX) than patients with mild bronchiectasis. R5 ≥0.43, resistance at 20 Hz (R20) ≥0.234, R5−R20 ≥28.3, AX ≥1.02, reactance at 5 Hz (X5) ≤−0.238, and Fres ≥20.88 revealed significant univariable relationships with bronchiectasis severity (p<0.05). Among these, only X5 ≤−0.238 exhibited a significant multivariable relationship with bronchiectasis severity (p=0.039). The receiver operating characteristic curve for predicting moderate-to-severe bronchiectasis of FACED score based on IOS parameters exhibited an area under the curve of 0.809. Conclusion The IOS assessed by the disease severity of FACED score can effectively reflect airway resistance and elasticity in bronchiectasis patients and serve as valuable tools for predicting bronchiectasis severity

A single nucleotide polymorphism in CAPN1 associated with marbling score in Korean cattle

<p>Abstract</p> <p>Background</p> <p>Marbling score (MS) is the major quantitative trait that affects carcass quality in beef cattle. In this study, we examined the association between genetic polymorphisms of the micromolar calcium-activated neutral protease gene (micro-calpain, <it>CAPN1</it>) and carcass traits in Korean cattle (also known as Hanwoo).</p> <p>Results</p> <p>By direct DNA sequencing in 24 unrelated Korean cattle, we identified 39 sequence variants within exons and their flanking regions in <it>CAPN1</it>. Among them, 12 common polymorphic sites were selected for genotyping in the beef cattle (<it>n </it>= 421). Statistical analysis revealed that a polymorphism in the 3'UTR (<it>c.2151*479C>T</it>) showed significant association with MS (<it>P</it>^{<it>cor</it>.}= 0.02).</p> <p>Conclusion</p> <p>Our findings suggest that polymorphisms in <it>CAPN1 </it>might be one of the important genetic factors involved in carcass quality in beef cattle, although it could be false positive association.</p

Acute Localized Exanthematous Pustulosis on the Face

Acute localized exanthematous pustulosis (ALEP) is a localized variant of acute generalized exanthematous pustulosis, which is characterized by the eruption of multiple scattered pustules following drug administration. A 26-year-old woman presented with multiple erythematous pustules on her face, which had appeared three days after taking antibiotics. Histopathological findings showed subcorneal pustules and mixed inflammatory cell infiltration in the dermis. The pustules were resolved within 2 weeks after the patient discontinued the antibiotics. Herein, we present a case of a woman with a cutaneous drug reaction consistent with ALEP that occurred subsequent to administration of antibiotics

Impact of AI-assisted CXR analysis in detecting incidental lung nodules and lung cancers in non-respiratory outpatient clinics

PurposeThe use of artificial intelligence (AI) for chest X-ray (CXR) analysis is becoming increasingly prevalent in medical environments. This study aimed to determine whether AI in CXR can unexpectedly detect lung nodule detection and influence patient diagnosis and management in non-respiratory outpatient clinics.MethodsIn this retrospective study, patients over 18 years of age, who underwent CXR at Yongin Severance Hospital outpatient clinics between March 2021 and January 2023 and were identified to have lung nodules through AI software, were included. Commercially available AI-based lesion detection software (Lunit INSIGHT CXR) was used to detect lung nodules.ResultsOut Of 56,802 radiographic procedures, 40,191 were from non-respiratory departments, with AI detecting lung nodules in 1,754 cases (4.4%). Excluding 139 patients with known lung lesions, 1,615 patients were included in the final analysis. Out of these, 30.7% (495/1,615) underwent respiratory consultation and 31.7% underwent chest CT scans (512/1,615). As a result of the CT scans, 71.5% (366 cases) were found to have true nodules. Among these, the final diagnoses included 36 lung cancers (7.0%, 36/512), 141 lung nodules requiring follow-up (27.5%, 141/512), 114 active pulmonary infections (22.3%, 114/512), and 75 old inflammatory sequelae (14.6%, 75/512). The mean AI nodule score for lung cancer was significantly higher than that for other nodules (56.72 vs. 33.44, p &lt; 0.001). Additionally, active pulmonary infection had a higher consolidation score, and old inflammatory sequelae had the highest fibrosis score, demonstrating differences in the AI analysis among the final diagnosis groups.ConclusionThis study indicates that AI-detected incidental nodule abnormalities on CXR in non-respiratory outpatient clinics result in a substantial number of clinically significant diagnoses, emphasizing AI’s role in detecting lung nodules and need for further evaluation and specialist consultation for proper diagnosis and management

Protective Effect of Hypoxic Preconditioning on Hypoxic-Ischemic Injured Newborn Rats

Brief episodes of cerebral hypoxia-ischemia cause transient ischemic tolerance to subsequent ischemic events that are otherwise lethal. This study was conducted to evaluate the protective effect of hypoxic preconditioning on hypoxic-ischemic injury in the neonatal rat and the persistence of a protective window after hypoxic preconditioning. The rats were preconditioned with hypoxia (8% oxygen, 92% nitrogen) for three hours, subjected to ischemia using ligation of the right common carotid artery, and then exposed to another three hours of hypoxia. Using proton magnetic resonance spectroscopy, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining, and morphologic scores, this study shows that hypoxic preconditioning 6-hr to 1-day before hypoxic-ischemic injury increases survival rates and has neuroprotective effects against subsequent hypoxic-ischemic injury. The mechanism of the protective effects of hypoxic preconditioning in the newborn rat brain may involve downregulation of apoptotic cell death