Hepatocellular carcinoma with characteristic mucin production: a case report

We present a unique case of hepatocellular carcinoma with mucin-producing gland formation. A 53-year-old man with hepatitis B infection presented with weight loss for the past month. Computed tomography demonstrated a 10 × 9.8 cm mass in the right hepatic lobe accompanied by cirrhotic changes in the hepatic parenchyma. Right hepatectomy was performed, and the tumor cut surface showed a poorly-circumscribed, white to pink tumor with numerous nodules and extensive necrosis. Microscopically, the tumor was composed of thick trabeculae and large, irregularly-shaped islands, both of which were filled with pleomorphic eosinophilic hepatoid cells or gland-forming columnar cells with mucin production. Those cells were immunoreactive for cytokeratin 19 in both the trabeculae and the glands. In some tumor cells, limited immunoreactivity for cytokeratin 7, epithelial membrane antigen and carcinoembryonic antigen was noted. The cells forming thick trabeculae were focally positive for hepatocyte paraffin 1 and alpha-fetoprotein. We suggest that this tumor shows bidirectional differentiation into hepatocytes and cholangiocytes, supporting the concepts that human hepatocarcinogenesis can be based on transformation of progenitor cells which can imply divergent differentiation

Low Skeletal Muscle Mass and Clinical Outcomes in Chronic Obstructive Pulmonary Disease

Background In patients with chronic obstructive pulmonary disease (COPD), decreased muscle mass is a frequently encountered comorbidity in clinical practice. However, the evaluation of muscle mass in patients with COPD in real-world practice is rare. Methods We retrospectively reviewed the electronic medical records of all patients with COPD who underwent bioelectrical impedance analysis at least once between January 2011 and December 2021 in three hospitals. Then, we analyzed the performance rate of muscle mass measurement in the patients and the correlation between muscle mass, clinical parameters, and COPD prognosis. Results Among the 24,502 patients with COPD, only 270 (1.1%) underwent muscle mass measurements. The total skeletal muscle mass index was significantly correlated with albumin, alanine transaminase, and creatinine to cystatin C ratio in patients with COPD (r=0.1614, p=0.011; r=0.2112, p=0.001; and r=0.3671, p=0.001, respectively). Acute exacerbation of COPD (AE COPD) was significantly correlated with muscle mass, especially the truncal skeletal muscle mass index (TSMI) in males (r=–0.196, p=0.007). In the multivariate analysis, TSMI and cystatin C were significant risk factors for AE COPD (hazard ratio, 0.200 [95% confidence interval, CI, 0.048 to 0.838] and 4.990 [95% CI, 1.070 to 23.278], respectively). Conclusion Low muscle mass negatively affects the clinical outcomes in patients with COPD. Despite its clinical significance, muscle mass measurement is performed in a small proportion of patients with COPD. Therefore, protocols and guidelines for the screening of sarcopenia in patients with COPD should be established

β-Caryophyllene attenuates dextran sulfate sodium-induced colitis in mice via modulation of gene expression associated mainly with colon inflammation

AbstractWe examined the modulatory activity of β-caryophyllene (CA) and gene expression in colitic colon tissues in a dextran sulfate sodium (DSS)-induced colitis model. Experimental colitis was induced by exposing male BALB/c mice to 5% DSS in drinking water for 7 days. CA (30 or 300mg/kg) was administered orally once a day together with DSS. CA administration attenuated the increases in the disease activity index, colon weight/length ratio, inflammation score, and myeloperoxidase activity in DSS-treated mice. Microarray analysis showed that CA administration regulated the expression in colon tissue of inflammation-related genes including those for cytokines and chemokines (Ccl2, Ccl7, Ccl11, Ifitm3, IL-1β, IL-28, Tnfrsf1b, Tnfrsf12a); acute-phase proteins (S100a8, Saa3, Hp); adhesion molecules (Cd14, Cd55, Cd68, Mmp3, Mmp10, Sema6b, Sema7a, Anax13); and signal regulatory proteins induced by DSS. CA significantly suppressed NF-κB activity, which mediates the expression of a different set of genes. These results suggest that CA attenuates DSS-induced colitis, possibly by modulating the expression of genes associated mainly with colon inflammation through inhibition of DSS-induced NF-κB activity

A Toxicological Study of HangAmDan-B in Mice

AbstractThe aim of the study was to define the toxicity of HangAmDan-B (HAD-B) in mice over the short and long term. HAD-B was studied in 1-week single and 5-week repeated oral dose toxicity tests on male Imprinting Control Region mice. Doses used in 1 week single oral dose toxicity tests were 0, 0.2, 1, 5, and 25 g/kg/day and those of repeated toxicity test were 0, 0.04, 0.2, 1, and 2 g/kg/day. Blood and urine samples were assayed and their morphology observed. Numerical data were compared using Mann-Whitney U test and analysis of variance. Significantly decreased red blood cell levels in mice from S2-HAD-B, S3-HAD-B, S4-HAD-B, and S5-HAD-B groups were observed in single oral dose toxicity tests. Hemoglobin, hematocrit, and mean cell hemoglobin values in mice from the S4-HAD-B and S5-HAD-B groups were also significantly decreased. No mortalities or significant differences in all factors were observed during the dosing period of the repeated dose toxicity test. Administering 2 g/kg/day of HAD-B in mice over a 5-week period showed no significant hematological changes. However, risk of anemia with more than 5 g/kg/ day administration of HAD-B was found. In general, HAD-B appears to be safe and nontoxic, and a no observed adverse effect level in mice was established at 2 g/kg/ day. This data serves as satisfactory preclinical evidence for the safety of HAD-B should a future clinical trial for HAD-B be launched. Further studies are required to confirm these safety results and to carry out a safety trial in humans

Maysin and Its Flavonoid Derivative from Centipedegrass Attenuates Amyloid Plaques by Inducting Humoral Immune Response with Th2 Skewed Cytokine Response in the Tg (APPswe, PS1dE9) Alzheimer\u27s Mouse Model

Alzheimer\u27s disease (AD) is a slow, progressive neurodegenerative disease and the most common type of dementia in the elderly. The etiology of AD and its underlying mechanism are still not clear. In a previous study, we found that an ethyl acetate extract of Centipedegrass (CG) (i.e., EA-CG) contained 4 types of Maysin derivatives, including Luteolin, Isoorientin, Rhamnosylisoorientin, and Derhamnosylmaysin, and showed protective effects against Amyloid beta (Aβ) by inhibiting oligomeric Aβ in cellular and in vitro models. Here, we examined the preventative effects of EA-CG treatment on the Aβ burden in the Tg (Mo/Hu APPswe PS1dE9) AD mouse model. We have investigated the EA-CG efficacy as novel anti-AD likely preventing amyloid plaques using immunofluorescence staining to visually analyze Aβ40/42 and fibril formation with Thioflavin-S or 6E10 which are the profile of immunoreactivity against epitope Aβ1-16 or neuritic plaque, the quantitation of humoral immune response against Aβ, and the inflammatory cytokine responses (Th1 and Th2) using ELISA and QRT-PCR. To minimize the toxicity of the extracted CG, we addressed the liver toxicity in response to the CG extract treatment in Tg mice using relevant markers, such as aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) measurements in serum. The EA-CG extract significantly reduced the Aβ burden, the concentration of soluble Aβ40/42 protein, and fibril formation in the hippocampus and cortex of the Tg mice treated with EA-CG (50 mg/kg BW/day) for 6 months compared with the Tg mice treated with a normal diet. Additionally, the profile of anti-inflammatory cytokines revealed that the levels of Th2 (interleukin-4 (IL-4) and interleukin-10 (IL-10)) cytokines are more significantly increased than Th1 (interferon-γ (IFN-γ), interleukin-2(IL-2)) in the sera. These results suggest that the EA-CG fraction induces IL-4/IL-10-dependent anti-inflammatory cytokines (Th2) rather than pro-inflammatory cytokines (Th1), which are driven by IL-2/IFN-γ. With regard to the immune response, EA-CG induced an immunoglobulin IgG and IgM response against the EA-CG treatment in the Tg mice. Furthermore, EA-CG significantly ameliorated the level of soluble Aβ42 and Aβ40. Similarly, we observed that the fibril formation was also decreased by EA-CG treatment in the hippocampus and cortex after quantitative analysis with Thioflavin-S staining in the Tg brain tissues. Taken together, our findings suggested that Maysin and its derivative flavonoid compounds in the EA-CG fraction might be beneficial therapeutic treatments or alternative preventative measures to adjuvant for boosting humoral and cellular include immune response and anti-inflammation which may lead to amyloid plaque accumulation in Alzheimer\u27s patients\u27 brains

Inhibition of T Cell Receptor Signal Transduction by Tyrosine Kinase–interacting Protein of Herpesvirus saimiri

T cells play a central role in orchestrating immunity against pathogens, particularly viruses. Thus, impairing T cell activation is an important strategy employed by viruses to escape host immune control. The tyrosine kinase–interacting protein (Tip) of the T lymphotropic Herpesvirus saimiri (HVS) is constitutively present in lipid rafts and interacts with cellular Lck tyrosine kinase and p80 endosomal protein. Here we demonstrate that, due to the sequestration of Lck by HVS Tip, T cell receptor (TCR) stimulation fails to activate ZAP70 tyrosine kinase and to initiate downstream signaling events. TCR ζ chains in Tip-expressing T cells were initially phosphorylated to recruit ZAP70 molecule upon TCR stimulation, but the recruited ZAP70 kinase was not subsequently phosphorylated, resulting in TCR complexes that were stably associated with inactive ZAP70 kinase. Consequently, Tip expression not only markedly inhibited TCR-mediated intracellular signal transduction but also blocked TCR engagement with major histocompatibility complexes on the antigen-presenting cells and immunological synapse formation. These results demonstrate that a lymphotropic herpesvirus has evolved a novel mechanism to deregulate T cell activation to disarm host immune surveillance. This process contributes to the establishment and maintenance of viral latency

Partial anomalous pulmonary venous connection with intact atrial septum in a child with ventricular septal defect: a case report

Partial anomalous pulmonary vein connection (PAPVC) is a rare congenital abnormal cardiac defect involving the pulmonary veins draining into the right atrium (RA) directly or indirectly by venous connection. Ninety percent of PAPVCs are accompanied by atrial septal defect (ASD). To our knowledge, there is no previous report of PAPVC with ventricular septal defect (VSD) without ASD in Korea, and in this paper, we report the first such case. A 2-day-old girl was admitted into the Chonnam National University Hospital for evaluation of a cardiac murmur. An echocardiogram revealed perimembranous VSD without ASD. She underwent patch closure of the VSD at 5 months of age. Although the VSD was completely closed, she had persistent cardiomegaly with right ventricular volume overload, as revealed by echocardiography. Three years later, cardiac catheterization and chest computed tomography revealed a PAPVC, with the right upper pulmonary vein draining into the right SVC. Therefore, correction of the PAPVC was surgically performed at 3 years of age. We conclude that it is important to suspect PAPVC in patients with right ventricular volume overload, but without ASD

Role of Amphipathic Helix of a Herpesviral Protein in Membrane Deformation and T Cell Receptor Downregulation

Lipid rafts are membrane microdomains that function as platforms for signal transduction and membrane trafficking. Tyrosine kinase interacting protein (Tip) of T lymphotropic Herpesvirus saimiri (HVS) is targeted to lipid rafts in T cells and downregulates TCR and CD4 surface expression. Here, we report that the membrane-proximal amphipathic helix preceding Tip's transmembrane (TM) domain mediates lipid raft localization and membrane deformation. In turn, this motif directs Tip's lysosomal trafficking and selective TCR downregulation. The amphipathic helix binds to the negatively charged lipids and induces liposome tubulation, the TM domain mediates oligomerization, and cooperation of the membrane-proximal helix with the TM domain is sufficient for localization to lipid rafts and lysosomal compartments, especially the mutivesicular bodies. These findings suggest that the membrane-proximal amphipathic helix and TM domain provide HVS Tip with the unique ability to deform the cellular membranes in lipid rafts and to downregulate TCRs potentially through MVB formation

Fabrication of AlGaN/GaN Fin-Type HEMT Using a Novel T-Gate Process for Improved Radio-Frequency Performance

To increase the radio-frequency (RF) performance of AlGaN/GaN-based fin-type high electron mobility transistors (HEMTs), a novel T-gate process was developed and applied to fabricate a device with high RF performance. In a single lithography process, the applied T-gate process shows a technique for forming a T-gate using the reactivity difference of several photoresists. The fabricated device has a steep fin width (W-fin) of 130 nm, a fin height (H-fin) of 250 nm, and a gate length (L-G) of 190 nm. The device exhibits a low leakage current (I-off) of 6.6 x 10(-10) A/mm and a high I-on/I-off current ratio of 4.7 x 10(8). Moreover, the fabricated device achieved a high cut-off frequency (f(T)) of 9.7 GHz and a very high maximum oscillation frequency (f(max)) of 27.8 GHz. The f(max) value of the proposed device is 138% higher than that of GaN-based fin-type HEMTs without T-gate.1