Inactivation Patterns of p16/INK4A in Oral Squamous Cell Carcinomas

The p16/INK4A is one of the major target genes in carcinogenesis and its inactivation has frequently been reported in other types of tumors. The purpose of this study is to evaluate inactivation patterns of p16/INK4A in oral squamous cell carcinoma. Six different oral cancer cell lines, SCC-4, SCC-9, SCC-15, SCC-25, KB, and SNUDH- 379 were examined for inactivation of p16/INK4A genes. In the analysis of p16/INK4A gene inactivation, PCR amplification, direct sequencing, and methylation-specific PCR methods were adopted for evaluation of homozygous deletion, point mutation, and promoter hypermethylation, respectively. Homozygous deletion was detected in SCC-25 and SCC-9. SCC-15 showed hypermethylated promoter region within p16/INK4A gene. It is suggestive in the present study that inactivation patterns of p16/INK4A were mainly homozygous deletion, promoter methylation rather than point mutation in oral squamous cancer cell lines, so treatment modalities of oral squamous cell carcinoma should be focused on these types of inactivation

ULTRAFILTRATED FRACTION OF KOREAN RED GINSENG EXTRACT IMPROVES MEMORY IMPAIRMENT OF TG2576 MICE VIA INHIBITION OF SOLUBLE AÎ’ PRODUCTION AND ACETYLCHOLINESTERASE ACTIVITY

Objective: The goal of this study was to research for an effective fraction on memory improvement of Korean red ginseng.Methods: In this study, 80 % ethanol red ginseng extract (RE) was divided into inner fluid (REUI) and outer fluid (REUO) by the ultrafiltration and then REUO was further separated into four fractions namely, REUO-00, REUO-30, REUO-50 and REUO-70, respectively, by Diaion HP-20 column chromatography.Results: REUO has protected more significantly the H2O2-induced SHSY-5Y cell death than REUI. Interestingly, the hydrophobic parts of the REUO (REUO-EtOHs) such as REUO-30,-50 and-70 decreased more significantly the H2O2-induced cell death than its hydrophilic part (REUO-00) in a dose-dependent manner. Then, we focused on the activity of a candidate for cholinergic functions, because memory deficits of neurodegenerative diseases are closely associated with cholinergic dysfunctions. The REUO-EtOHs (1.25 mg/ml) inhibited the activity of the acetylcholinesterase and its half maximal inhibitory concentration (IC50) was about 2.358 mg/ml. Additionally, we investigated whether the intake of the REUO (50 mg/kg/d) during 12 w could improve memory impairment of 12-month old Tg2576 mice and decrease total soluble amyloid-β (Aβ) proteins in the mouse brain cortex. The REUO alleviated significantly the memory impairment and successfully reduced the levels of the soluble Aβ proteins in the mouse cortex.Conclusion: We finally suggest that the REUO, including majorly its hydrophobic part that may be considered as more effective for memory improvement, will be highly considered as valuable candidate for the memory-enhancing ingredients against cholinergic dysfunctions and cognitive impairments of neurodegenerative diseases including Alzheimer's disease.Keywords: Ginseng, Alzheimer's disease, Acetylcholinesterase, Ultrafiltration, MemoryÂ

Multimodality Imaging Can Help to Doubt, Diagnose and Follow-Up Cardiac Mass

Primary cardiac lymphoma is a very rare form of lymphoma primarily or mainly involving the heart, as in the two cases presented in this report. Various imaging modalities, including coronary computed tomography angiography, cardiac magnetic resonance imaging and positron emission tomography were useful for the characterization and diagnosis of cardiac mass. Pathologic confirmation was successful with endomyocardial biopsy under echocardiographic guidance, intra- and extracardiacally. In primary cardiac lymphoma, diagnosis using multiple modalities may be useful for mass characterization, and for response monitoring after chemotherapy

Humulus japonicus attenuates LPS-and scopolamine-induced cognitive impairment in mice

Background : Neuroinflammation plays an important role in cognitive decline and memory impairment in neurodegenerative disorders. Previously, we demonstrated that Humulus japonicus (HJ) has anti-inflammatory effects in rodent models of Alzheimer’s disease and Parkinson’s disease. The present study aimed to examine the protective potential of HJ extracts against lipopolysaccharide (LPS)-induced cognitive impairment and scopolamine-induced amnesia in mouse models. Cognitive improvement of mice was investigated by novel object recognition test. For analyzing effects on neuroinflammation, immunohistochemistry and quantitative real-time polymerase chain reaction (qRT-PCR) assays were performed. Results : We found that the oral administration of HJ significantly improved cognitive dysfunction induced by LPS in a novel object recognition test. The LPS-induced activation of microglia was notably decreased by HJ treatment in the cortex and hippocampus. HJ administration with LPS also significantly increased the mRNA expression of interleukin (IL)-10 and decreased the mRNA expression of IL-12 in the parietal cortex of mice. The increased expression of LPS-induced complement C1q B chain (C1bq) and triggering receptor expressed on myeloid cells 2 (Trem2) genes was significantly suppressed by HJ treatment. In addition, HJ administration significantly improved novel object recognition in a scopolamine-induced amnesia mouse model. Conclusions : These findings revealed that HJ has a beneficial effect on cognitive impairment and neuroinflammation induced by systemic inflammation and on amnesia induced by scopolamine in mice.This study was supported by the KRIBB Research Initiative Program of the Republic of Korea (KGS1042221) and the Development of Platform Technology for Innovative Medical Measurements funded by Korea Research Institute of Standards and Science (KRISS-GP2022-2)

Reversible Pulmonary Hypertension in Adolescent with Left Atrial Myxoma

We report a patient of left atrial huge myxoma presenting with severe pulmonary hypertension in adolescents. A patient was a 14-year-old boy presented with sudden onset dyspnea. Transthoracic echocardiographic study revealed the presence of a nodular, 4.34 × 8.11 cm sized, mobile, hyperechoic mass in the left atrium and severe pulmonary hypertension with tricuspid insufficiency. After surgical therapy, tricuspid regurgitation and pulmonary hypertension was decreased and the patient was stabilized and had an uneventful clinical course

Antiviral activity of furanocoumarins isolated from Angelica dahurica against influenza a viruses H1N1 and H9N2

Ethnopharmacological relevance: Angelica dahurica (Hoffm.) Benth. & Hook.f. ex Franch. & Say. (Umbelliferae family) is an herbaceous, perennial plant native to northern and eastern Asia. The root of A. dahurica has traditionally been used under the name "Bai Zhi" as a medicinal plant for colds, dizziness, ulcers, and rheumatism. Moreover, it is also an important ingredient of various prescriptions, such as Gumiganghwal-Tang, for the common cold and influenza. Aim of the study: Even though various biological activities of the root of A. dahurica have been reported along with its chemical components, the detailed mechanism of how it exerts anti-influenza activity at the compound level has not been studied. Therefore, we investigated the anti-influenza properties of furanocoumarins purified by bioactivity-guided isolation. Materials and methods: Bioactivity-guided isolation from a 70% EtOH extract of the root of A. dahurica was performed to produce four active furanocoumarins. The inhibition of cytopathic effects (CPEs) was evaluated to ascertain the antiviral activity of these compounds against influenza A (H1N1 and H9N2) viruses. The most potent compound was subjected to detailed mechanistic studies such as the inhibition of viral protein synthesis, CPE inhibition in different phases of the viral replication cycle, neuraminidase (NA) inhibition, antiapoptotic activity using flow cytometry, and immunofluorescence. Results: The bioactivity-guided isolation produced four active furanocoumarins, isoimperatorin (1), oxypeucedanin (2), oxypeucedanin hydrate (3) and imperatorin (4) from the n-BuOH fraction. Among them, compound 2 (followed by compounds 1, 4 and 3) showed a significant CPE inhibition effect, which was stronger than that of the positive control ribavirin, against both H1N1 and H9N2 with an EC50 (mu M) of 5.98 +/- 0.71 and 4.52 +/- 0.39, respectively. Compound 2 inhibited the synthesis of NA and nucleoprotein (NP) in a dose-dependent manner. In the time course assays, the cytopathic effects of influenza A-infected MDCK cells were reduced by 80-90% when treated with compound 2 for 1 and 2 h after infection and declined drastically 3 h after infection. The level of viral NA and NP production was markedly reduced to less than 20% for both proteins in compound 2 (20 mu M)-treated cells compared to untreated cells at 2 h after infection. In the molecular docking analysis, compound 2 showed a stronger binding affinity for the C-terminus of polymerase acidic protein (PAC; - 36.28 kcal/mol) than the other two polymerase subunits. Compound 2 also exerted an antiapoptotic effect on virus infected cells and significantly inhibited the mRNA expression of caspase-3 and Bax. Conclusion: Our results suggest that compound 2 might exert anti-influenza A activity via the inhibition of the early phase of the viral replication cycle, not direct neutralization of surface proteins, such as hemagglutinin and NA, and abnormal apoptosis induced by virus infection. Taken together, these findings suggest that furanocoumarins predominant in A. dahurica play a pivotal role in its antiviral activity. These findings can also explain the reasons for the ethnopharmacological uses of this plant as an important ingredient in many antiviral prescriptions in traditional Chinese medicine (TCM).N

Neuroprotective effects of triterpenoids from camellia japonica against amyloid beta-induced neuronal damage

Alzheimer's disease (AD), a neurocognitive impairment affecting human mental capacity, is related to the accumulation of amyloid-beta peptide (A beta) and the hyperphosphorylation of tau protein. In addition to modern therapies approved for AD treatment, natural products with antioxidant and anti-inflammatory properties have been studied for their potential to prevent AD pathogenesis. Six new noroleanane triterpenoids from the fruit peels of Camellia japonica were isolated, and their structures were determined by diverse spectroscopic methods. The APP neuroprotective effects of the six new compounds were tested against A beta-induced neurotoxicity and neuroinflammation in mouse hippocampal and microglial cells. In the model of HT22-transfected cells, compounds 1-4 showed strongly neuroprotective effects via antioxidant response element gene activation and decreased the level of glutamate uptake. Compounds 1-4 also appeared to have strong inhibitory effects on NO production in A beta(1-42)-transfected BV2 microglial cells. A docking simulation study was used to explain the inhibitory effects of compounds 1-4 on beta-secretase 1 (BACE1). Noroleanane triterpenoids 1 - 4 had potential neuroprotective and anti-inflammatory effects against A beta-induced neuronal damage. The structure-activity relationships of the 30 oleanane triterpenoids from C. japonica were assessed in a model of A beta(1-42)-transfected HT22 cells.N

Sicyos angulatus ameliorates atherosclerosis through downregulation of aortic inflammatory responses in apolipoprotein E-deficient mice

Sicyos angulatus (SA), a summer annual vine originating from Northeastern USA, is a widely distributed noxious invasive plant. However, the clinical application of SA has not been investigated previously. The purpose of present study was to determine the effects of SA on atherosclerosis and its underlying mechanism. Atherosclerosis was induced by feeding apolipoprotein E-deficient (apoE(-/-)) mice with an atherogenic diet for 8 weeks. SA was administered daily by oral gavage during induction of atherosclerosis. ApoE(-/-) mice treated with SA demonstrated a significant reduction in atherosclerotic plaque area in the whole aorta and aortic sinus compared with vehicle-treated mice. The plasma lipid profiles, including triglyceride, total cholesterol, high-density lipoprotein and low-density lipoprotein, were not affected by SA administration. Of note, gene expression levels of proatherogenic cytokines including tumor necrosis factor alpha (Tnf alpha) and interleukin-6 (Il-6) were significantly decreased in the aorta of SA administered apoE(-/-) mice. In lipopolysaccharide-stimulated RAW 264.7 macrophage cells, SA also inhibited the induction Tnfa, Il-6 and Il-1 beta in a dose-dependent manner. Furthermore, gene expression levels of endothelial cell adhesion molecules, including vascular cell adhesion protein 1 and intercellular adhesion molecule 1 were reduced in the aorta of apoE(-/-) mice treated with SA, which was followed by diminished aortic infiltration of monocytes/macrophages. In conclusion, to the best of our knowledge, this is the first study to demonstrate that SA is able to suppress the development of atherosclerosis by inhibiting the aortic expression of proinflammatory factors in atherogenic diet-fed apoE(-/-) mice. The present study may provide novel insights into the application of the environmentally problematic weed SA as a therapeutically effective natural product for preventing atherosclerosis.N

Causal effects of atrial fibrillation on brain white and gray matter volume: a Mendelian randomization study

Background Atrial fibrillation (AF) and brain volume loss are prevalent in older individuals. We aimed to assess the causal effect of atrial fibrillation on brain volume phenotypes by Mendelian randomization (MR) analysis. Methods The genetic instrument for AF was constructed from a previous genome-wide association study (GWAS) meta-analysis (15,993 AF patients and 113,719 controls of European ancestry). The outcome summary statistics for head-size-normalized white or gray matter volume measured by magnetic resonance imaging were provided by a previous GWAS of 33,224 white British participants in the UK Biobank. Two-sample MR by the inverse variance–weighted method was performed, supported by pleiotropy-robust MR sensitivity analysis. The causal estimates for the effect of AF on ischemic stroke were also investigated in a dataset that included the findings from the MEGASTROKE study (34,217 stroke patients and 406,111 controls of European ancestry). The direct effects of AF on brain volume phenotypes adjusted for the mediating effect of ischemic stroke were studied by multivariable MR. Results A higher genetic predisposition for AF was significantly associated with lower grey matter volume [beta −0.040, standard error (SE) 0.017, P=0.017], supported by pleiotropy-robust MR sensitivity analysis. Significant causal estimates were identified for the effect of AF on ischemic stroke (beta 0.188, SE 0.026, P=1.03E−12). The total effect of AF on lower brain grey matter volume was attenuated by adjusting for the effect of ischemic stroke (direct effects, beta −0.022, SE 0.033, P=0.528), suggesting that ischemic stroke is a mediator of the identified causal pathway. The causal estimates were nonsignificant for effects on brain white matter volume as an outcome. Conclusions This study identified that genetic predisposition for AF is significantly associated with lower gray matter volume but not white matter volume. The results indicated that the identified total effect of AF on gray matter volume may be mediated by ischemic stroke.This work was supported by a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HW20C2066). The funder played no role in the conduct of the study, and the study was performed independently by the authors