Pathological Evaluation of Porcine Circovirus 2d (PCV2d) Strain and Comparative Evaluation of PCV2d and PCV2b Inactivated Vaccines against PCV2d Infection in a Specific Pathogen-Free (SPF) Yucatan Miniature Pig Model.

Porcine circovirus type 2 (PCV2) is an economically important swine pathogen that causes porcine circovirus-associated diseases (PCVADs). The objective of this study was to evaluate the use of specific pathogen-free Yucatan miniature pigs (YMPs) as an experimental model for PCV2d challenge and vaccine assessment because PCV2-negative pigs are extremely rare in conventional swine herds in Korea. In the first experiment, every three pigs were subjected to PCV2d field isolate or mock challenge.

Comparison of the pathogenicity of porcine reproductive and respiratory syndrome virus (PRRSV)-1 and PRRSV-2 in pregnant sows.

To date, few studies related to the evaluation of the pathogenicity of different PRRSV isolates using a reproductive model have been undertaken, and the main focus has remained on respiratory models using young pigs. This study aimed to evaluate the pathogenicity of two PRRSV-1 isolates (D40 and CBNU0495) and two PRRSV-2 isolates (K07-2273 and K08-1054) in a reproductive model. Pregnant sows were experimentally infected with PRRSV at gestational day 93 or used as an uninfected negative control.

Evaluation of the Cross-Protective Efficacy of a Chimeric PRRSV Vaccine against Two Genetically Diverse PRRSV2 Field Strains in a Reproductive Model.

Despite the routine use of porcine reproductive and respiratory syndrome (PRRS)-modified live vaccines, serious concerns are currently being raised due to their quick reversion to virulence and limited cross-protection against divergent PRRS virus (PRRSV) strains circulating in the field. Therefore, a PRRS chimeric vaccine (JB1) was produced using a DNA-launched infectious clone by replacing open reading frames (ORFs) 3-6 with those from a mixture of two genetically different PRRSV2 strains (K07-2273 and K08-1054) and ORF1a with that from a mutation-resistant PRRSV strain (RVRp22) exhibiting an attenuated phenotype. To evaluate the safety and cross-protective efficacy of JB1 in a reproductive model, eight PRRS-negative pregnant sows were purchased and divided into four groups.

Efficacy of Porcine Epidemic Diarrhea Vaccines: A Systematic Review and Meta-Analysis.

Porcine epidemic diarrhea (PED) is a devastating disease that causes considerable economic damage to the global pig industry. Although the causative agent, the porcine epidemic diarrhea virus (PEDV), was identified about a half century ago, there is still much debate on the preventive measures against the disease, especially regarding the PED vaccine. Recent reports on PEDV variants make the vaccination for PEDV more confusing.

Diet control to achieve euglycaemia induces tau hyperphosphorylation via AMPK activation in the hippocampus of diabetic rats.

Alzheimer's disease (AD) is a chronic neurodegenerative disease, and typical pathologic findings include abnormally hyperphosphorylated tau aggregation and neurofibrillary tangles. Insulin resistance and hyperglycaemia have been proposed as risk factors for AD development. As the maintenance of optimal blood glucose level is an important indicator of diabetes mellitus (DM) treatment, diet control is essential.

Generation and protective efficacy of a cold-adapted attenuated genotype 2b porcine epidemic diarrhea virus.

The recent emergence and re-emergence of porcine epidemic diarrhea virus (PEDV) underscore the urgent need for the development of novel, safe, and effective vaccines against the prevailing strain. In this study, we generated a cold-adapted live attenuated vaccine candidate (Aram-P29-CA) by short-term passage of a virulent PEDV isolate at successively lower temperatures in Vero cells. Whole genome sequencing identified 12 amino acid changes in the cold-adapted strain with no insertions and deletions throughout the genome.

Heterogeneity in liver histopathology is associated with GSK-3β activity and mitochondrial dysfunction in end-stage diabetic rats on differential diets.

While liver histopathology is heterogeneous in diabetes, the underlying mechanisms remain unclear. We investigated whether glycemic variation resulting from differential diets can induce heterogeneity in diabetic liver and the underlying molecular mechanisms. We generated end-stage non-obese diabetic model rats by subtotal-pancreatectomy in male Sprague- Dawley rats and ad libitum diet for 7 weeks (n = 33).

Molecular characteristics and pathogenic assessment of porcine epidemic diarrhoea virus isolates from the 2018 endemic outbreaks on Jeju Island, South Korea.

Since the 2013-2014 incursion of the virulent G2b porcine epidemic diarrhoea virus (PEDV) pandemic strains in South Korea, frequent moderate-scale regional outbreaks have recurred. In particular, areas of Jeju Island with extensive swine production have faced repeated epidemics since the re-emergence in 2014. The current study reports the complete genome sequences and molecular characterization of the representative PEDV strains responsible for the 2018 endemic outbreaks on Jeju Island.

Assessment of the safety and efficacy of an attenuated live vaccine based on highly virulent genotype 2b porcine epidemic diarrhea virus in nursing piglets.

We have previously reported the generation of the attenuated KNU-141112-S DEL5/ORF3 virus by continuous propagation of highly virulent G2b porcine epidemic diarrhea virus (PEDV) in Vero cells. The present study aimed to assess the safety of S DEL5/ORF3 and to evaluate its effectiveness as a live vaccine for prime-booster vaccinations. Reversion to virulence experiments revealed that the S DEL5/ORF3 strain retains its attenuated phenotype and genetic stability after five successive passages in susceptible piglets.

Phenotypic and genotypic analyses of an attenuated porcine reproductive and respiratory syndrome virus strain after serial passages in cultured porcine alveolar macrophages.

The porcine reproductive and respiratory syndrome virus (PRRSV) is a globally ubiquitous swine viral pathogen that causes major economic losses worldwide. We previously reported an over-attenuated phenotype of cell-adapted PRRSV strain CA-2-P100 . In the present study, CA-2-P100 was serially propagated in cultured porcine alveolar macrophage (PAM) cells for up to 20 passages to obtain the derivative strain CA-2-MP120.

Genetic characteristics, pathogenicity, and immunogenicity associated with cell adaptation of a virulent genotype 2b porcine epidemic diarrhea virus.

Porcine epidemic diarrhea virus (PEDV) has emerged or re-emerged worldwide, posing a significant financial threat to major pig-producing countries. In the present study, a virulent Korean pandemic PEDV strain, KNU-141112, was serially propagated in Vero cells for up to 100 passages. Through cell culture adaptation, we obtained four distinct deletion (DEL) mutants by plaque purification followed by nucleotide sequencing of the spike (S)/ORF3 gene-coding region, which were designated KNU-141112-S DEL2, -S DEL5, -S DEL2/ORF3, and -S DEL5/ORF3.

Effects of hydrogen peroxide on voltage-dependent K(+) currents in human cardiac fibroblasts through protein kinase pathways.

Human cardiac fibroblasts (HCFs) have various voltage-dependent K(+) channels (VDKCs) that can induce apoptosis. Hydrogen peroxide (H2O2) modulates VDKCs and induces oxidative stress, which is the main contributor to cardiac injury and cardiac remodeling. We investigated whether H2O2 could modulate VDKCs in HCFs and induce cell injury through this process.

Pathogenicity and genetic characteristics associated with cell adaptation of a virulent porcine reproductive and respiratory syndrome virus nsp2 DEL strain CA-2.

Porcine reproductive and respiratory syndrome virus (PRRSV) is the most common and world-widespread viral pathogen of swine. We previously reported genomic sequences and pathogenicity of type 2 Korean PRRSV strains belonging to the virulent lineage 1 family, which contain remarkable amino acid deletions in nonstructural protein 2 (nsp2 DEL) compared to VR-2332. Here, a virulent type 2 Korean PRRSV nsp2 DEL strain, CA-2, was serially propagated in MARC-145 cells for up to 100 passages (CA-2-P100).

Identification of novel therapeutic target genes in acquired lapatinib-resistant breast cancer by integrative meta-analysis.

Acquired resistance to lapatinib is a highly problematic clinical barrier that has to be overcome for a successful cancer treatment. Despite efforts to determine the mechanisms underlying acquired lapatinib resistance (ALR), no definitive genetic factors have been reported to be solely responsible for the acquired resistance in breast cancer. Therefore, we performed a cross-platform meta-analysis of three publically available microarray datasets related to breast cancer with ALR, using the R-based RankProd package.

Euglycemia in Diabetic Rats Leads to Reduced Liver Weight via Increased Autophagy and Apoptosis through Increased AMPK and Caspase-3 and Decreased mTOR Activities.

Euglycemia is the ultimate goal in diabetes care to prevent complications. However, the benefits of euglycemia in type 2 diabetes are controversial because near-euglycemic subjects show higher mortality than moderately hyperglycemic subjects. We previously reported that euglycemic-diabetic rats on calorie-control lose a critical liver weight (LW) compared with hyperglycemic rats.

Topological network analysis of differentially expressed genes in cancer cells with acquired gefitinib resistance.

Background/aim: Despite great effort to elucidate the process of acquired gefitinib resistance (AGR) in order to develop successful chemotherapy, the precise mechanisms and genetic factors of such resistance have yet to be elucidated.

Materials And Methods: We performed a cross-platform meta-analysis of three publically available microarray datasets related to cancer with AGR. For the top 100 differentially expressed genes (DEGs), we clustered functional modules of hub genes in a gene co-expression network and a protein-protein interaction network.

Integrative meta-analysis of multiple gene expression profiles in acquired gemcitabine-resistant cancer cell lines to identify novel therapeutic biomarkers.

In molecular-targeted cancer therapy, acquired resistance to gemcitabine is a major clinical problem that reduces its effectiveness, resulting in recurrence and metastasis of cancers. In spite of great efforts to reveal the overall mechanism of acquired gemcitabine resistance, no definitive genetic factors have been identified that are absolutely responsible for the resistance process. Therefore, we performed a cross-platform meta-analysis of three publically available microarray datasets for cancer cell lines with acquired gemcitabine resistance, using the R-based RankProd algorithm, and were able to identify a total of 158 differentially expressed genes (DEGs; 76 up- and 82 down-regulated) that are potentially involved in acquired resistance to gemcitabine.

Cross-platform meta-analysis of multiple gene expression profiles identifies novel expression signatures in acquired anthracycline-resistant breast cancer.

Anthracyclines are among the most effective and commonly used chemotherapeutic agents. However, the development of acquired anthracycline resistance is a major limitation to their clinical application. The aim of the present study was to identify differentially expressed genes (DEGs) and biological processes associated with the acquisition of anthracycline resistance in human breast cancer cells.

Diet control to achieve euglycemia induces significant loss of heart and liver weight via increased autophagy compared with ad libitum diet in diabetic rats.

Intensive glucose control increases the all-cause mortality in type 2 diabetes mellitus (T2DM); however, the underlying mechanisms remain unclear. We hypothesized that strict diet control to achieve euglycemia in diabetes damages major organs, increasing the mortality risk. To evaluate effects on major organs when euglycemia is obtained by diet control, we generated a model of end-stage T2DM in 13-week-old Sprague-Dawley rats by subtotal pancreatectomy, followed by ad libitum feeding for 5 weeks.

Genomic analysis and pathogenic characteristics of Type 2 porcine reproductive and respiratory syndrome virus nsp2 deletion strains isolated in Korea.

Porcine reproductive and respiratory syndrome virus (PRRSV) is a globally ubiquitous swine virus that exhibits genetic and pathogenic heterogeneity among isolates. The present study was conducted to determine the complete genome sequence and pathogenicity of two Korean type 2 PRRSV nonstructural protein 2 (nsp2) deletion mutants, CA-2 and KNU-12-KJ4. The full-length genomes of CA-2 and KNU-12-KJ4 were determined to be 15,018 and 15,019 nucleotides in length, excluding the poly(A) tail, respectively, which were 393- or 392-nucleotide shorter than that of the type 2 NA prototype strain VR-2332 due to the presence of notable large deletions within the nsp2 gene.

Role of the mixed-lineage protein kinase pathway in the metabolic stress response to obesity.

Saturated free fatty acid (FFA) is implicated in the metabolic response to obesity. In vitro studies indicate that FFA signaling may be mediated by the mixed-lineage protein kinase (MLK) pathway that activates cJun NH2-terminal kinase (JNK). Here, we examined the role of the MLK pathway in vivo using a mouse model of diet-induced obesity.

Improvement of β-cell function after achievement of optimal glycaemic control via long-term continuous subcutaneous insulin infusion therapy in non-newly diagnosed type 2 diabetic patients with suboptimal glycaemic control.

Background: Achieving euglycaemia by continuous subcutaneous insulin infusion (CSII) therapy alone has been shown to restore β-cell function in patients with newly diagnosed type 2 diabetes. However, the efficacy has not been evaluated in patients with non-newly diagnosed type 2 diabetes and suboptimal glycaemic control.

Methods: Of the 1220 patients with type 2 diabetes who began CSII therapy from March 2000 to March 2007, we retrospectively selected patients using the following inclusion criteria: glycosylated haemoglobin (HbA1c ) ≥ 7.

Insulin requirement profiles of patients with type 2 diabetes after achieving stabilized glycemic control with short-term continuous subcutaneous insulin infusion.

Background: As in type 1 diabetes, continuous subcutaneous insulin infusion (CSII) therapy is emerging as a promising therapeutic option in type 2 diabetes. However, the insulin requirement profiles of patients with type 2 diabetes when treated via CSII with rapid-acting insulin analogs have not been well investigated.

Methods: We examined insulin requirement profiles of type 2 diabetes patients (n = 300; age, 57.

The ginsenoside-Rb2 lowers cholesterol and triacylglycerol levels in 3T3-L1 adipocytes cultured under high cholesterol or fatty acids conditions.

The effects of the ginsenoside Rb2 (Rb2) on lipid metabolism were characterized in 3T3-L1 adipocytes to evaluate their utility for treating obesity. While the amounts of total cholesterol and triacylglycerol (TAG) were markedly increased in the adipocytes treated with high amounts of cholesterol and fetal bovine serum (FBS), the test groups treated with Rb2 showed levels that were close to normal. The effect of Rb2 on these cells was comparable to that of lovastatin.

Improvement of cardiovascular risk factors in patients with type 2 diabetes after long-term continuous subcutaneous insulin infusion.

Background: The effects of long-term continuous subcutaneous insulin infusion (CSII) on cardiovascular risk factors such as hyperglycaemia, dyslipidaemia, and proinflammatory cytokine levels have not been assessed so far in type 2 diabetes.

Methods: We analysed the levels of HbA(1c), serum lipids, tumor necrosis factor alpha (TNF-alpha), and interleukin 6 (IL-6) at 0, 2, and 30 weeks after CSII in 15 patients with type 2 diabetes (mean age, 53.3+/-10.