Anti-inflammatory effects of Radix Gentianae Macrophyllae (Qinjiao), Rhizoma Coptidis (Huanglian) and Citri Unshiu Pericarpium (Wenzhou migan) in animal models

<p>Abstract</p> <p>Background</p> <p>KHU14, an ethanolic extract of <it>Radix Gentianae Macrophyllae </it>(<it>Qinjiao</it>), <it>Rhizoma Coptidis </it>(<it>Huanglian</it>) and <it>Citri Unshiu Pericarpium </it>(<it>Wenzhou migan</it>) was tested for its anti-inflammatory effects.</p> <p>Methods</p> <p>Three out of 20 herbs were found to have anti-inflammatory effects. The formulation of these herbs, i.e. KHU14 was tested for croton oil-induced ear edema, carrageenan-induced paw edema, acetic acid-induced capillary permeability, cotton pellet and delayed type hypersensitivity.</p> <p>Results</p> <p>KHU14 exhibited anti-inflammatory effects in animal models of acute and chronic inflammation. The anti-inflammatory activity of KHU14 observed was comparable to that of celecoxib. KHU14 inhibited the production of NO and PGE₂in LPS/IFN-gamma-stimulated peritoneal macrophages, and reduced edema and the amount of infiltrated cells in animal models.</p> <p>Conclusion</p> <p>KHU14 exhibited anti-inflammatory effects as demonstrated in typical immunological tests for anti-inflammation <it>in vitro </it>and <it>in vivo</it>.</p

Epidemiology of Traumatic Head Injury in Korean Children

The aim of this study was to elucidate the epidemiology of traumatic head injury (THI) among Korean children. A prospective, in-depth trauma survey was conducted in five teaching hospitals. Data from all of the children who attended the emergency department (ED) were analyzed. From June 2008 to May 2009, 2,856 children with THI visited the 5 EDs. The average age of the subjects was 5.6 (SD ± 4.9) yr old, and 1,585 (55.5%) were 0-4 yr old. The male-to-female ratio was 2.3 to 1 (1,979 vs 877). Consciousness levels of the subjects were classified according to the Glasgow Coma Scale (GCS), and 99.1%, 0.6%, and 0.4% were determined as mild, moderate, or severe injury, respectively, according to the GCS categorization. Most injuries occurred at home (51.3%), and the most common mechanism of injury was collision (43.2%). With regard to outcome, 2,682 (93.9%) patients were sent home, and 35 (1.2%) were transferred to another hospital. A total of 133 (4.7%) patients were hospitalized, and 38 (1.3%) underwent surgery. The incidence and characteristics of pediatric THI in Korea are affected by sex, location and injury mechanism

Pre-Operative Prediction of Advanced Prostatic Cancer Using Clinical Decision Support Systems: Accuracy Comparison between Support Vector Machine and Artificial Neural Network

OBJECTIVE: The purpose of the current study was to develop support vector machine (SVM) and artificial neural network (ANN) models for the pre-operative prediction of advanced prostate cancer by using the parameters acquired from transrectal ultrasound (TRUS)-guided prostate biopsies, and to compare the accuracies between the two models. MATERIALS AND METHODS: Five hundred thirty-two consecutive patients who underwent prostate biopsies and prostatectomies for prostate cancer were divided into the training and test groups (n = 300 versus n = 232). From the data in the training group, two clinical decision support systems (CDSSs-[SVM and ANN]) were constructed with input (age, prostate specific antigen level, digital rectal examination, and five biopsy parameters) and output data (the probability for advanced prostate cancer [> pT3a]). From the data of the test group, the accuracy of output data was evaluated. The areas under the receiver operating characteristic (ROC) curve (AUC) were calculated to summarize the overall performances, and a comparison of the ROC curves was performed (p < 0.05). RESULTS: The AUC of SVM and ANN is 0.805 and 0.719, respectively (p = 0.020), in the pre-operative prediction of advanced prostate cancer. CONCLUSION: The performance of SVM is superior to ANN in the pre-operative prediction of advanced prostate cancer.ope

YH29407 with anti-PD-1 ameliorates anti-tumor effects via increased T cell functionality and antigen presenting machinery in the tumor microenvironment

Among cancer cells, indoleamine 2, 3-dioxygenase1 (IDO1) activity has been implicated in improving the proliferation and growth of cancer cells and suppressing immune cell activity. IDO1 is also responsible for the catabolism of tryptophan to kynurenine. Depletion of tryptophan and an increase in kynurenine exert important immunosuppressive functions by activating regulatory T cells and suppressing CD8+ T and natural killer (NK) cells. In this study, we compared the anti-tumor effects of YH29407, the best-in-class IDO1 inhibitor with improved pharmacodynamics and pharmacokinetics, with first and second-generation IDO1 inhibitors (epacadostat and BMS-986205, respectively). YH29407 treatment alone and anti-PD-1 (aPD-1) combination treatment induced significant tumor suppression compared with competing drugs. In particular, combination treatment showed the best anti-tumor effects, with most tumors reduced and complete responses. Our observations suggest that improved anti-tumor effects were caused by an increase in T cell infiltration and activity after YH29407 treatment. Notably, an immune depletion assay confirmed that YH29407 is closely related to CD8+ T cells. RNA-seq results showed that treatment with YH29407 increased the expression of genes involved in T cell function and antigen presentation in tumors expressing ZAP70, LCK, NFATC2, B2M, and MYD88 genes. Our results suggest that an IDO1 inhibitor, YH29407, has enhanced PK/PD compared to previous IDO1 inhibitors by causing a change in the population of CD8+ T cells including infiltrating T cells into the tumor. Ultimately, YH29407 overcame the limitations of the competing drugs and displayed potential as an immunotherapy strategy in combination with aPD-1

Ketogenic diet-induced extension of longevity in epileptic Kcna1-null mice is influenced by gender and age at treatment onset.

Sudden unexpected death in epilepsy (SUDEP) is a leading cause of premature mortality in patients with epilepsy, and has been linked to multiple risk factors, including gender and early age at seizure onset. Despite the lack of a targeted therapy for SUDEP, it has recently been shown that a high-fat, low carbohydrate ketogenic diet (KD) enhances longevity in the epileptic Kcna1-null (KO) mouse, a validated model of SUDEP. Here, we asked whether the KD-driven prolongation of lifespan in KO mice is dependent on sex and/or age at treatment onset. We found that as KO mice aged, their daily seizure frequency steadily increased, but had early demise by postnatal day (PD) 46.9±0.8. In KO mice started on the KD at PD30, longevity was extended to a mean of PD69.8±1.7, accompanied with improved seizure control. Interestingly, while seizure control on the KD was similar between male and female mice, KD-fed female KO mice survived longer than their male counterparts. Further, epileptic mice initiated on the KD at PD25 had longer lifespans compared to those placed on the KD starting at PD35. Collectively, these data further support the notion that the KD can retard disease progression and sudden death in KO mice, but that this beneficial action is influenced by gender and age at the start of treatment

Adrenocorticotropic hormone protects learning and memory function in epileptic Kcna1-null mice.

ACTH, a member of the melanocortin family of peptides, is often used in the treatment of the developmental epileptic encephalopathy spectrum disorders including, Ohtahara, West, Lennox Gastaut and Landau-Kleffner Syndromes and electrical status epilepticus of sleep. In these disorders, although ACTH is often successful in controlling the seizures and/or inter-ictal EEG abnormalities, it is unknown whether ACTH possesses other beneficial effects independent of seizure control. We tested whether ACTH can ameliorate the intrinsic impairment of hippocampal-based learning and memory in epileptic Kcna1-null (KO) mice. We found that ACTH - administered in the form of Acthar Gel given i.p. four times daily at a dose of 4 IU/kg (16 IU/kg/day) for 7days - prevented impairment of long-term potentiation (LTP) evoked with high-frequency stimulation in CA1 hippocampus and also restored spatial learning and memory on the Barnes maze test. However, with this treatment regimen, ACTH did not exert a significant effect on the frequency of spontaneous recurrent seizures. Together, our findings indicate that ACTH can ameliorate memory impairment in epileptic Kcna1-null mice separate from seizure control, and suggest that this widely used peptide may exert direct nootropic effects in the epileptic brain