Expression of TNF-and TGF-1 in the Rat Brain After a Single High-Dose IrradiationCytokines and growth factors are important regulatory proteins controlling the growth and differentiation of normal and malignant glial cells. In this study, we investigated the expression and origin of tumor necrosis factor-(TNF-) and transforming growth factor-1 (TGF-1) in the subacute brain injury after a single high-dose irradiation using 60 Sprague-Dawley rats. The right cerebral hemispheres of rats were exposed to a single 10 Gy dose of gamma rays using Ir-192. The radiation effect was assessed at 1 week, 2 weeks, 4 weeks, 6 weeks, and 8 weeks after irradiation, and the results were compared with those in sham operation group. Histological changes characteristic of radiation injury were correlated with the duration after the single dose irradiation. The loss of cortical thickness also increased with the lapse of time after irradiation. The TNF-expression in the irradiated cerebral hemispheres was significantly increased compared with that in the sham operation group. TGF-1 expression was also increased in the irradiated hemispheres. Immunohistochemical study revealed that TGF-1 was expressed predominantly by infiltrating macrophages and astrocytes around the necrotic areas. These findings indicate that TNF-and TGF-1 may play prominent roles in the radiation injuries after a single high-dose irradiation.

BackgroundKorean ginseng is a well-known medicinal herb that has been widely used in traditional medicine to treat various diseases, including asthma. Ginseng can be classified as white ginseng (WG) or red ginseng (RG), according to processing conditions. In this study, the authors compared the efficacies of these two ginseng types in a mouse model of acute asthma.MethodsTo produce the acute asthma model, BALB/c mice were sensitized with ovalbumin (OVA) and aluminum hydroxide, and then challenged with OVA. WG and RG extracts were administered to mice orally. The influences of WG and RG on airway hyperresponsiveness (AHR), immune cell distributions in bronchoalveolar lavage fluid (BALF), and OVA-specific immunoglobulin E (IgE), IgG1, and IgG2a in serum were investigated. Cytokine production by lymphocytes isolated from peribronchial lymph nodes and histopathological changes was also examined.ResultsIn OVA-sensitized mice, both WG and RG reduced AHR and suppressed immune cell infiltration in bronchoalveolar regions. BALF OVA-specific IgE levels were significantly lower in RG-treated OVA-sensitized mice than in the OVA-sensitized control group. WG and RG also suppressed inflammatory cytokine production by peribronchial lymphocytes. Histopathological findings showed reduced inflammatory cell infiltration and airway remodeling (e.g., epithelial hyperplasia) in WG- and RG-treated OVA mice compared with OVA controls.ConclusionIn this study, WG and RG showed antiasthmatic effects in an OVA-sensitized mouse model, and the efficacies of RG were found to be better than those of WG.

We aimed to discover and validate urinary exosomal proteins as biomarkers for antibody−mediated rejection (ABMR) after kidney transplantation. Urine and for-cause biopsy samples from kidney transplant recipients were collected and categorized into the discovery cohort (n = 36) and a validation cohort (n = 65). Exosomes were isolated by stepwise ultra-centrifugation for proteomic analysis to discover biomarker candidates for ABMR (n = 12). Of 1820 exosomal proteins in the discovery cohort, four proteins were specifically associated with ABMR: cystatin C (CST3), serum paraoxonase/arylesterase 1, retinol-binding protein 4, and lipopolysaccharide−binding protein (LBP). In the validation cohort, the level of urinary exosomal LBP was significantly higher in the ABMR group (n = 25) compared with the T-cell-mediated rejection (TCMR) group and the no major abnormality (NOMOA) group. Urinary exosomal CST3 level was significantly higher in the ABMR group compared with the control and NOMOA groups. Immunohistochemical staining showed that LBP and CST3 in the glomerulus were more abundant in the ABMR group compared with other groups. The combined prediction probability of urinary exosomal LBP and CST3 was significantly correlated with summed LBP and CST3 intensity scores in the glomerulus and peritubular capillary as well as Banff g + ptc scores. Urinary exosomal CST3 and LBP could be potent biomarkers for ABMR after kidney transplantation.

Diospyros kaki (D. kaki) has been cultivated throughout Eastern Asia for hundreds of years. D. kaki contains various biological active compounds, such as amino acids, carotenoids, flavonoids, tannins, catechins and vitamin A. Previous studies have shown that D. kaki has beneficial effects on homeostasis, constipation, hypertension, atherosclerosis and allergic dermatitis and is a good source of antioxidants, polyphenols and dietary fiber. However, the anti-allergic and anti-inflammatory effects of D. kaki have not yet been elucidated. This study aimed to investigate the protective effects of the aqueous extract of Diospyros kaki (AEDK) on mast cell-mediated allergic inflammation and to determine its possible mechanisms of action by using in vitro and in vivo mast cell-based models. The cAMP and intracellular calcium levels were measured to clarify the mechanisms by which AEDK inhibits the release of histamine from mast cells. AEDK inhibited the release of histamine and β-hexosaminidase from mast cells by modulating cAMP and intracellular calcium levels. We also measured the expression of pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β. AEDK decreased gene expression and the secretion of the pro-inflammatory cytokines, TNF-α and IL-1β by inhibiting nuclear factor-κB. In addition, AEDK inhibited systemic and cutaneous allergic reaction. The inhibitory effects of AEDK on allergic reaction and the release of histamine were found to be similar to those of disodium cromoglycate, a known anti-allergic drug. To isolate the active component of AEDK, activity-guided fractionation was performed, based on the inhibitory effects on systemic anaphylaxis. Catechin was identified as an active compound. The present findings provide evidence that AEDK inhibits allergic inflammation and suggest the therapeutic application of AEDK in allergic inflammatory disorders.

In this report, we describe a case of multiple brain abscesses associated with diffuse congenital pulmonary arteriovenous malformations (PAVM). Although the cases of brain abscesses associated with congenital PAVM are very rare, the brain abscess could be an initial clinical manifestation in asymptomatic PAVM as in the case presented in this report. PAVM may contribute to the development of a brain abscess by allowing easy bacterial access to systemic circulation through the right-to-left pulmonary vascular shunt, bypassing the filtering effect of the pulmonary capillaries. Hence, this association should be considered in cases with brain abscesses of undetermined etiologic factors.

The impact of the coronavirus disease 2019 (COVID-19) vaccination on humoral and cellular immunity in transplant recipients remains unknown. We report the case of a 78-year-old kidney transplant recipient who experienced acute T cell-mediated rejection after receiving the second dose of the BNT162b2 mRNA COVID-19 vaccine (Pfizer-BioN-Tech). She had no history of acute rejection throughout the 13 years after deceased donor kidney transplantation. Fifteen days after receiving the second dose of the BNT162b2 vaccine, the recipient visited our center with a mild headache and fever. Her serum creatinine level had increased from 0.61 to 4.95 mg/dL. Kidney allograft biopsy indicated acute T cell-mediated rejection (grade IB) with no pathologic evidence of antibody-mediated rejection. Anti-severe acute respiratory syndrome coronavirus 2 spike-immunoglobulin G and -immunoglobulin M measurements were weak positive and negative, respectively. Careful monitoring of kidney allograft function is vital for transplant recipients undergoing COVID-19 vaccination.

Background Patients receiving ABO-incompatible (ABOi) or human leukocyte antigen (HLA)-incompatible (HLAi) kidney transplantation (KT) require potent immunosuppression and are thus at a higher risk of infectious complications. We evaluated the clinical outcomes of KT stratified by ABO and HLA incompatibilities and identified the factors associated with the clinical outcomes. Material/Methods Recipients who underwent living-related KT between 2012 and 2017 were included and classified into 4 groups: ABO-compatible and HLA-compatible (ABOc/HLAc), HLA-incompatible (ABOc/HLAi), ABO-incompatible (ABOi/HLAc), and ABO-incompatible and HLA-incompatible (ABOi/HLAi). Cox proportional hazards regression analyses were carried out to evaluate the risk factors of acute rejection. Out of the 1732 patients who underwent KT, 1190, 131, 358, and 53 were in the ABOc/HLAc, ABOi/HLAc, ABOc/HLAi, and ABOi/HLAi groups, respectively. Results The ABO/HLAi group showed the lowest 5-year graft survival rate (91.7%). Death-censored graft survival was not significantly different among the groups. The mortality rate from infections was significantly higher in the ABOi/HLAi group (7.5%) than the other groups. Antibody-mediated rejection-free graft survival was the lowest in the ABOi/HLAi group, with significant differences compared with the ABOi/HLAc group ( P =0.02) and the ABOc/HLAi group ( P =0.03). ABOi/HLAi (hazard ratio [HR], 2.63; 95% confidence interval [CI], 1.04–6.65; P <0.01) and combined infection (HR, 1.91; 95% CI, 1.45–2.51; P <0.01) were significant risk factors for acute rejection. Conclusions Patients with both ABO and HLA incompatibilities showed inferior rates of overall patient and graft survival due to infectious complications. Infection was a prominent risk factor of acute rejection following KT after adjusting for possible confounders including ABO and HLA incompatibility.

Context: Ephedrae Herba (EH), the dried stems and leaves of Ephedra sinica Stapf., E. intermedia Schrenk et C. A. Mey., or E. equisetina Bge. (Ephedraceae [Ephedra]) is used to treat respiratory diseases. Recently, especially in the Republic of Korea, EH has also been used for weight reduction. Objective: We evaluated the effects and molecular targets of methanol EH extract (EHM) on high-fat diet (HFD)-induced hyperlipidemic ICR mice. Materials and methods: EHM was orally administered (100 mg/kg body weight/day) for 3 weeks. We observed changes in body weight (BW), total cholesterol (TC), high-density lipoprotein-cholesterol, and triglycerides to evaluate the physiological changes induced by HFD or EHM administration. To evaluate lipid peroxidation and liver toxicity, malondialdehyde and blood alanine aminotransferase levels were measured. In addition to analyzing liver gene expression profiles, EHM target proteins were identified using a protein interaction database. Results: EHM administration for 3 weeks significantly (p < 0.05) decreased TC and triglyceride levels without altering BW in mice, and gene expression levels in the livers of EHM-treated mice were restored at 34.0% and 48.4% of those up-or down-regulated by hyperlipidaemia, respectively. Proteins related to DNA repair and energy metabolism were identified via protein interaction network analysis as molecular targets of EHM that play key roles in ameliorating hyperlipidaemia. Discussion and conclusions: EHM regulated hyperlipidaemia by decreasing total blood lipid and triglyceride levels in hyperlipidaemic mice. EHM showed preventive effects against hyperlipidaemia in mice, possibly via the regulation of DNA repair and the expression of energy metabolism-related genes and proteins.