Genetic Diversity of Domestic Cat Hepadnavirus in Southern Taiwan.

Domestic cat hepadnavirus (DCH) is an infectious disease associated with chronic hepatitis in cats, which suggests a similarity with hepatitis B virus infections in humans. Since its first identification in Australia in 2018, DCH has been reported in several countries with varying prevalence rates, but its presence in Taiwan has yet to be investigated. In this study, we aimed to identify the presence and genetic diversity of DCH infections in Taiwan. Among the 71 samples tested, eight (11.27%) were positive for DCH. Of these positive cases, three cats had elevated levels of alanine transaminase (ALT) and aspartate transaminase (AST), suggesting an association between DCH infection and chronic hepatitis. Four DCH-positive samples were also tested for feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) coinfection. One sample (25%) was positive for FIV, whereas there was no positive sample for FeLV (0%). In addition, we performed whole genome sequencing on six samples to determine the viral genome sequences. Phylogenetic analyses identified a distinct lineage compared with previously reported sequences. This study highlights the importance of continuous surveillance of DCH and further research to elucidate the pathophysiology and transmission route of DCH.

Utilizing Proteomic Approaches to Uncover the Neuroprotective Effects of ACE Inhibitors: Implications for Alzheimer's Disease Treatment.

Two types of angiotensin-converting enzyme (ACE) inhibitors, lisinopril and benazepril HCl, were tested in neuroblastoma cells and found to upregulate low-density lipoprotein-receptor-related protein 1B (LRP1B) and 14-3-3 protein zeta/delta. Additionally, benazepril HCl was found to increase the expression of calreticulin. The upregulation of these proteins by ACE inhibitors may contribute to the amelioration of cognitive deficits in Alzheimer's disease/dementia, as well as the clinically observed deceleration of functional decline in Alzheimer's patients. This discovery suggests that the supplementation of ACE inhibitors may promote neuronal cell survival independently of their antihypertensive effect. Overall, these findings indicate that ACE inhibitors may be a promising avenue for developing effective treatments for Alzheimer's disease.

Immune Response Related to Lymphadenopathy Post COVID-19 Vaccination.

Mass vaccination against coronavirus disease 2019 (COVID-19) is a global health strategy to control the COVID-19 pandemic. With the increasing number of vaccinations, COVID-19 vaccine-associated lymphadenopathy (C19-VAL) has been frequently reported. Current findings emphasize the characteristics of C19-VAL. The mechanism of C19-VAL is complicated to explore. Accumulated reports separately show that C19-VAL incidence is associated with receiver age and gender, reactive change within lymph nodes (LN), etc. We constructed a systematic review to evaluate the associated elements of C19-VAL and provide the mechanism of C19-VAL. Articles were searched from PubMed, Web of Science and EMBASE by using the processing of PRISMA. The search terms included combinations of the COVID-19 vaccine, COVID-19 vaccination and lymphadenopathy. Finally, sixty-two articles have been included in this study. Our results show that days post-vaccination and B cell germinal center response are negatively correlated with C19-VAL incidence. The reactive change within LN is highly related to C19-VAL development. The study results suggested that strong vaccine immune response may contribute to the C19-VAL development and perhaps through the B cell germinal center response post vaccination. From the perspective of imaging interpretation, it is important to carefully distinguish reactive lymph nodes from metastatic lymph node enlargement through medical history collection or evaluation, especially in patients with underlying malignancy.

The Effects of Prior Mammography Screening on the Performance of Breast Cancer Detection in Taiwan.

The aim of this study was to investigate the influence of previous mammography screening on the performance of breast cancer detection. The screened women were divided into first-visit and follow-up groups for breast cancer screening. The positive predictive value (PPV), cancer detection rate (CDR), and recall rate were used to evaluate and analyze the overall screening performance among the two groups. Among them, 10,040 screenings (67.2%) were first visits and 4895 screenings (32.8%) were follow-up visits. The proportion of positive screening results for first-visit participants was higher than that for their follow-up counterparts (9.3% vs. 4.0%). A total of 98 participants (74 first-visit and 24 follow-up visit) were confirmed to have breast cancer. The PPV for positive mammography for women who underwent biopsy confirmation was 28.7% overall, reaching 35.8% for the follow-up visit group and 27.0% for the first-visit group. The CDR was 6.6 per 1000 overall, reaching 7.4 per 1000 for first-visit group and 4.9 per 1000 for the follow-up group. The overall recall rate was 7.9%, reaching 9.7% for the first-visit group and 4.2% for the follow-up group. The PPV is improved and the recall rate is decreased if prior mammography images are available for comparison when conducting mammography screening for breast cancer. By this study, we concluded that prior mammography plays an important role for breast cancer screening, while follow-up mammography may increase the diagnostic rate when compared to the prior mammography. We suggest that the public health authority can encourage subjects to undergo screenings in the same health institute where they regularly visit.

Utilizing an Animal Model to Identify Brain Neurodegeneration-Related Biomarkers in Aging.

Glycine N-methyltransferase (GNMT) regulates S-adenosylmethionine (SAMe), a methyl donor in methylation. Over-expressed SAMe may cause neurogenic capacity reduction and memory impairment. GNMT knockout mice (GNMT-KO) was applied as an experimental model to evaluate its effect on neurons. In this study, proteins from brain tissues were studied using proteomic approaches, Haemotoxylin and Eosin staining, immunohistochemistry, Western blotting, and ingenuity pathway analysis. The expression of Receptor-interacting protein 1(RIPK1) and Caspase 3 were up-regulated and activity-dependent neuroprotective protein (ADNP) was down-regulated in GNMT-KO mice regardless of the age. Besides, proteins related to neuropathology, such as excitatory amino acid transporter 2, calcium/calmodulin-dependent protein kinase type II subunit alpha, and Cu-Zn superoxide dismutase were found only in the group of aged wild-type mice; 4-aminobutyrate amino transferase, limbic system-associated membrane protein, sodium- and chloride-dependent GABA transporter 3 and ProSAAS were found only in the group of young GNMT-KO mice and are related to function of neurons; serum albumin and Rho GDP dissociation inhibitor 1 were found only in the group of aged GNMT-KO mice and are connected to neurodegenerative disorders. With proteomic analyses, a pathway involving Gonadotropin-releasing hormone (GnRH) signal was found to be associated with aging. The GnRH pathway could provide additional information on the mechanism of aging and non-aging related neurodegeneration, and these protein markers may be served in developing future therapeutic treatments to ameliorate aging and prevent diseases.

Prognostic Value of 18F-FDG PET/CT Volume-Based Metabolic Parameters in Patients with Node-Negative Stage II Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is a major cancer prevalent in Asian males. Pretreatment tumor burden can be prognostic for ESCC. We studied the prognostic value of metabolic parameters of 2-deoxy-2-[18F] fluoro-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) and the serum squamous cell carcinoma antigen (SCC-Ag) level in node-negative stage II ESCC patients. Eighteen males underwent staging evaluation were included. The volume-based metabolic parameters derived from 18F-FDG PET/CT, including metabolic tumor volume (MTV) and total lesion glycolysis (TLG), were obtained using the PET Volume Computer Assisted Reading application. The Spearman correlation coefficients were calculated to assess the relationship between metabolic parameters and pretreatment serum SCC-Ag levels. Based on the 5-year follow-up, patients were sub-divided into the demised and the stable groups. Potential prognostic value was assessed by independent t-test and the Mann-Whitney U test. The association of overall survival was assessed using univariate and multivariate Cox regression analyses. The demised group showed significant higher values in serum SCC-Ag, as well as in MTV and TLG, but not SUVmax and SUVmean. The SUVmax, MTV, TLG, and serum SCC-Ag showed significant association with overall survival. Our findings suggest potential usage of pretreatment volume-based metabolic parameters of 18F-FDG PET/CT and serum SCC-Ag as prognostic factors for node-negative stage II ESCC patients.

Influence of pigeon interferon alpha (PiIFN-α) on pigeon circovirus (PiCV) replication and cytokine expression in Columba livia.

Pigeon circovirus (PiCV) is the most diagnosed virus in pigeons (Columba livia) and have been studied and reported globally. PiCV infections can lead to immunosuppression and pigeons infected with PiCV can result to lymphocyte apoptosis and atrophy of immune organs. Young pigeon disease syndrome (YPDS) is a complex disease and believed that PiCV could be one of the agents leading to this syndrome. An effective treatment regimen is needed to control the spread of PiCV in pigeons. In this study pigeon interferon alpha (PiIFN-α) was cloned and expressed and its antiviral effects were tested against fowl adenovirus type 4 (FAdV-4) in vitro and PiCV in vivo. No detectable levels of FAdV-4 viral genome in LMH cells stimulated with 300 µg/mL PiIFN-α were found. Additionally, PiIFN-α was stable at different temperature and pH for 4 h, and no reduction in antiviral activity was observed in untreated and treated cells. In pigeons naturally and experimentally infected by PiCV, no detectable levels of PiCV virus titers were found after treatment with PiIFN-α. Cytokine and ISG expression levels in liver and spleen samples were detected and IFN-γ and Mx1 genes were dominantly up-regulated following PiIFN-α treatment (p < 0.05). This study demonstrated that PiCV can be inhibited by administration of PiIFN-α and PiFN-α can be used as a therapeutic approach to prevent the spread of PiCV in pigeons.

Cdc20 and molecular chaperone CCT2 and CCT5 are required for the Muscovy duck reovirus p10.8-induced cell cycle arrest and apoptosis.

This study demonstrates that the Muscovy duck reovirus (MDRV) p10.8 protein is one of many viral non-structural proteins that induces both cell cycle arrest and apoptosis. The p10.8 but not σC is a nuclear targeting protein that shuttles between the nucleus and the cytoplasm. Our results reveal that p10.8-induced apoptosis in cultured cells occurs by the nucleoporin Tpr/p53-dependent and Fas/caspase 8-mediated pathways. Furthermore, a compelling finding from this study is that the p10.8 and σC proteins of MDRV facilitate CDK2 and CDK4 degradation via the ubiquitin-proteasome pathway. We found that depletion of Cdc20 reversed the p10.8- and σC- mediated CDK4 degradation and p10.8-induced apoptosis, suggesting that Cdc20 plays a critical role in modulating p10.8-mediated cell cycle and apoptosis. Furthermore, we found that depletion of chaperonin-containing tailless complex polypeptide 1 (CCT) 2 and CCT5 reduced the level of Cdc20 and reversed the p10.8- and σC-mediated CDK4 degradation and p10.8-induced apoptosis, indicating that molecular chaperone CCT2 and CCT5 are required for stabilization of Ccd20 for mediating both cell cycle arrest and apoptosis. This study provides mechanistic insights into how p10.8 induces both cell cycle arrest and apoptosis.

Dust levels of polybrominated diphenyl ethers (PBDEs) and polybrominated dibenzo-p-dioxins/furans (PBDD/Fs) in the Taiwanese elementary school classrooms: Assessment of the risk to school-age children.

Elementary school classroom dust is an important source of exposure to polybrominated dibenzo-p-dioxins/furans and diphenyl ethers (PBDD/DF/DEs) for school-age children. Our goal is thus to investigate concentrations of PBDD/DF/DEs in elementary school classroom dust to further assess the impact on school-age children via ingestion. The dust from classrooms, including both normal (NR) and computer classrooms (CR), was collected from six urban and four rural schools. Fourteen PBDEs and twelve PBDD/Fs were measured using high-resolution gas-chromatography/high-resolution mass-spectrometry. The mean levels of Σ14PBDEs in NR and CR dust from the urban classrooms were 370 and 2510ng/g and those whose dust from the rural classrooms were 464 and 1780ng/g. The means of ΣPBDD/Fs were 0.0401ng-WHO2005-TEQ/g (concentration: 4.72ng/g) in urban NR dust, 0.0636ng-WHO2005-TEQ/g (7.51ng/g) in urban CR dust, 0.0281ng-WHO2005TEQ/g (3.60ng/g) in rural NR dust, and 0.0474ng-WHO2005TEQ/g (6.28ng/g) in rural CR dust. The PBDEs pattern in NR dust was quite different from that in CR dust, but the PBDD/Fs patterns in NR and CR dust were similar. A linearly significant correlation coefficient (n=20, r=0.862, p<0.001) was found between ΣPBDEs and ΣPBDD/Fs in NR and CR dust, indicating that the PBDEs and PBDD/Fs in the dust may be from the same sources in the elementary school classrooms. This study assessed the risks (daily intake and cancer and non-cancer risks) of PBDEs and PBDD/Fs for the children from the classroom dust, and the calculated risk values did not exceed the related thresholds. With regard to the exposure scenarios for school-age children in an indoor environment, the results suggest that they might ingest more dust PBDD/DF/DEs in their homes than in the schools. In conclusion, the exposure of Taiwanese elementary school children to PBDD/DF/DEs via indoor dust was with a safe range based on our findings.

Estrogenic effects in the influents and effluents of the drinking water treatment plants.

Estrogen-like endocrine disrupting compounds (EEDC) such as bisphenol A, nonylphenol, and phthalic acid esters are toxic compounds that may occur in both raw- and drinking water. The aim of this study was to combine chemical- and bioassay to evaluate the risk of EEDCs in the drinking water treatment plants (DWTPs). Fifty-six samples were collected from seven DWTPs located in northern-, central-, and southern Taiwan from 2011 to 2012 and subjected to chemical analyses and two bioassay methods for total estrogenic activity (E-Screen and T47D-KBluc assay). Among of the considered EEDCs, only dibutyl phthalate (DBP) and di (2-ethylhexyl) phthalate (DEHP) were detected in both drinking and raw water samples. DBP levels in drinking water ranged from

An AhR-Luciferase Adenovirus Infection System for Rapid Screening of Dioxins in Soils.

Our goal was to develop a fast-screening method for measuring dioxin levels in soils. The adenovirus (Ad)-dioxin-responsive (DR) bioassay system (AdEasy-6XDRE-TATA-Luc) combined with a fast-cleanup system was examined under conventional conditions (i.e., with incubation at 37°C) and three alternative conditions [incubation at 37°C with addition of phorbol-12-myristate-13-acetate (PMA), incubation at 33°C, and incubation at 33°C with addition of PMA]. The best conditions for carrying out the Ad-DR bioassay was 33°C and no addition of PMA. The background level of soil dioxins determined by the chemical assay [6.49 ng I-TEQ/kg dry weight (dw)] was well correlated (Pearson's r = 0.873, p < 0.001) with that by the Ad-DR bioassay [expressed in ng bioanalytical equivalents (BEQ) 81.1 ng BEQ/kg dw] (n = 17). When surveyed in contaminated soil samples (n = 114) from industrial areas by the Ad-DR bioassay, dioxin levels were 117, 102, 98.5, and 112 ng BEQ/kg dw, respectively, in northern, central, southern, and eastern Taiwan.

Avian Reovirus Protein p17 Functions as a Nucleoporin Tpr Suppressor Leading to Activation of p53, p21 and PTEN and Inactivation of PI3K/AKT/mTOR and ERK Signaling Pathways.

Avian reovirus (ARV) protein p17 has been shown to regulate cell cycle and autophagy by activation of p53/PTEN pathway; nevertheless, it is still unclear how p53 and PTEN are activated by p17. Here, we report for the first time that p17 functions as a nucleoporin Tpr suppressor that leads to p53 nuclear accumulation and consequently activates p53, p21, and PTEN. The nuclear localization signal (119IAAKRGRQLD128) of p17 has been identified for Tpr binding. This study has shown that Tpr suppression occurs by p17 interacting with Tpr and by reducing the transcription level of Tpr, which together inhibit Tpr function. In addition to upregulation of PTEN by activation of p53 pathway, this study also suggests that ARV protein p17 acts as a positive regulator of PTEN. ARV p17 stabilizes PTEN by stimulating phosphorylation of cytoplasmic PTEN and by elevating Rak-PTEN association to prevent it from E3 ligase NEDD4-1 targeting. To activate PTEN, p17 is able to promote ß-arrestin-mediated PTEN translocation from the cytoplasm to the plasma membrane via a Rock-1-dependent manner. The accumulation of p53 in the nucleus induces the PTEN- and p21-mediated downregulation of cyclin D1 and CDK4. Furthermore, Tpr and CDK4 knockdown increased virus production in contrast to depletion of p53, PTEN, and LC3 reducing virus yield. Taken together, our data suggest that p17-mediated Tpr suppression positively regulates p53, PTEN, and p21 and negatively regulates PI3K/AKT/mTOR and ERK signaling pathways, both of which are beneficial for virus replication.

Effect of Arctium lappa L. in the dextran sulfate sodium colitis mouse model.

AIM: To analyze the possible protective role of Arctium lappa L. (AL) in a murine model of ulcerative colitis (UC). METHODS: BALB/c mice were administered 100 mg/kg AL powder orally each day. After 7 d, colitis was induced by administration of dextran sulfate sodium (DSS) (5% W/V) in drinking water for a further 8 consecutive days. Diarrhea and bloody stools as well as colonic histology were observed. The level of interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) in colonic sections were detected by immunohistochemistry. RESULTS: There were significant differences in mean body weight values and disease activity indices between controls and AL-treated animals. Moreover, the histological findings showed that AL treatment can prevent mucosal edema, submucosal erosions, ulceration, inflammatory cell infiltration and colon damage. In addition, immunohistochemistry analysis showed that the levels of the inflammatory cytokines, IL-6 and TNF-alpha were also decreased in AL-treated groups. CONCLUSION: We suggest that AL can prevent intestinal damage and decrease inflammatory cytokines in mice with DSS-induced colitis. Thus, AL could prove to be a useful food for UC.

Advanced glycation end products down-regulate gap junctions in human hepatoma SKHep 1 cells via the activation of Src-dependent ERK1/2 and JNK/SAPK/AP1 signaling pathways.

Hyperglycemia and advanced glycation end products (AGEs) are associated with an elevated risk of developing several cancers in diabetic patients. However, the detailed mechanisms remain to be elucidated. The mechanism of AGE-bovine serum albumin (BSA) on gap junction intercellular communication in human hepatoma cell line, SKHep 1, was investigated. Both Cx32 and Cx43 are major gap junction forming proteins in the liver, the loss of which has been shown to facilitate tumorigenesis. Although the MTT assay results showed that AGE-BSA significantly increased cell growth by 31%, AGE-BSA down-regulated Cx32 and Cx43 expression in a dose- and time-dependent manner. The present study also demonstrated that ERK1/2 and JNK/SAPK were significantly activated by AGE-BSA and that Src, ERK1/2, and JNK/SAPK inhibitors significantly reversed the reduction of Cx32 and Cx43 proteins by AGE-BSA. Taken together, these results strongly support the hypothesis that Src-dependent ERK1/2 and JNK/SAPK/AP1 signaling pathways play a key role in AGE-BSA-mediated down-regulation of Cx32 and Cx43 protein expression in SKHep 1 cells.

Superoxide activates very late antigen-4 on an eosinophil cell line and increases cellular binding to vascular cell adhesion molecule-1.

The recruitment of eosinophils to the airway is a key event in the pathogenesis of allergy. Very late antigen-4 (VLA-4), an integrin ligand for vascular cell adhesion molecule-1 (VCAM-1), is expressed on eosinophils. VLA-4-mediated adhesion of eosinophils to VCAM-1 may contribute to their selective recruitment to tissues in allergy. Reactive oxygen species (ROS), including nitric oxide (NO), are abundant in the airway of allergic patients, but their role in pathogenesis of allergy is unclear. In this investigation, we studied the effects of ROS on integrin-mediated eosinophil adhesion. Recombinant soluble VCAM-1 and ICAM-1 were used to test the effects of ROS on the integrin-mediated adhesion of an eosinophil cell line. We used phorbol 12-myristate 13-acetate-stimulated neutrophils and hypoxanthine to generate superoxide, NO donors as sources of NO, and a static cell-to-protein adhesion assay to analyze cellular adhesion. Stimulated neutrophils significantly increased eosinophil binding to VCAM-1, which was reversed in the presence of superoxide dismutase. Neutrophils from a chronic granulomatous disease patient lacked this activity in enhancing eosinophil adhesion. Our results suggest that the balance between ROS molecules in different tissue microenvironments may change the integrin-mediated leukocyte adhesion and is likely to be a key factor in leukocyte recruitment in allergic inflammation.