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"Lin, Hao-Wei"
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Amplification of SMYD3 promotes tumorigenicity and intrahepatic metastasis of hepatocellular carcinoma via upregulation of CDK2 and MMP2
2019
SMYD3, a member that belongs to the SET and MYND-domain (SMYD) family, has also been proven to largely participate in gene transcription regulation and progression of several human cancers as a histone lysine methyltransferase. However, the role and significance of SMYD3 in both the clinic and progression of hepatocellular carcinoma (HCC) remain unclear. Herein, we find that SMYD3 is increased in cirrhotic livers, and strikingly upregulated in hepatocellular carcinoma (HCC) tissues and cell lines. Subsequent analyses suggest that high expression level of SMYD3 significantly correlates with the malignant characteristics of HCC, and predicts poor prognosis in patients. Our results show that overexpression of SMYD3 increases, while silencing of SMYD3 inhibits, cell proliferation, invasiveness and tumorigenicity both in vitro and in vivo. SMYD3 also promotes intrahepatic metastasis of HCC cells. For the mechanisms, we identify that SMYD3 bound to CDK2 and MMP2 promoter and increased H3K4me3 modification at the corresponding promoters to promote gene transcription. Importantly, pharmacological targeting of SMYD3 with BCI-121 inhibitor effectively repressed the tumorigenicity of HCC cells. Finally, our results show that gene locus amplification is a cause for SMYD3 overexpression in HCC. These findings not only uncover that SMYD3 overexpression promotes the tumorigenicity and intrahepatic metastasis of HCC cell via upregulation of CDK2 and MMP2, but also suggest SMYD3 could be a practical prognosis marker or therapeutic target against the disease.
Journal Article
Phylogeographic and genetic characterization of porcine circovirus type 2 in Taiwan from 2001–2017
2019
Porcine circovirus type 2 (PCV2) is an important pathogen that causes significant economic losses in the swine industry worldwide. Five major PCV2 genotypes have been identified, including PCV2a, PCV2b, PCV2c, PCV2d, and PCV2e. To investigate the prevalence and phylodynamics of the different PCV2 genotypes in Taiwan, 214 PCV2 ORF2 sequences from Taiwan and other countries were analyzed. Genotypic differences were observed among PCV2a, 2b, and 2d at amino acid position 89 in ORF2, with isoleucine (I), arginine (R), and leucine (L), respectively. Similar to other countries, a genotypic shift was also observed in Taiwan, where the predominant genotype shifted from PCV2b to 2d after 2010. The estimated nucleotide substitution rate of Taiwanese strains in the ORF2 region was 8.467 × 10
−4
substitutions per site per year. This rapid evolution rate of PCV2 may lead to the genotypic shift observed in Taiwan. The times to the most recent common ancestor (TMRCA) for PCV2a, -2b, and -2d-2 was dated to 1970, 1992 and 2004, respectively. Thus, the PCV2a, -2b, and -2d genotypes were already present in Taiwan before the introduction of the PCV2 vaccine.
Journal Article
Reversible Luminescent Switching Induced by Heat/Water Treatment in a Zero-Dimensional Hybrid Antimony(Ⅲ) Chloride
2023
Recently zero-dimensional (0-D) inorganic–organic metal halides (IOMHs) have become a promising class of optoelectronic materials. Herein, we report a new photoluminescent (PL) 0-D antimony(III)-based IOMH single crystal, namely [H2BPZ][SbCl5]·H2O (BPZ = benzylpiperazine). Photophysical characterizations indicate that [H2BPZ][SbCl5]·H2O exhibits singlet/triplet dual-band emission. Density functional theory (DFT) calculations suggest that [H2BPZ][SbCl5]·H2O has the large energy difference between singlet and triplet states, which might induce the dual emission in this compound. Temperature-dependent PL spectra analyses suggest the soft lattice and strong electron–phonon coupling in this compound. Thermogravimetric analysis shows that the water molecules in the lattice of the title crystal could be removed by thermal treatment, giving rise to a dehydrated phase of [H2BPZ][SbCl5]. Interestingly, such structural transformation is accompanied by a reversible PL emission transition between red light (630 nm, dehydrated phase) and yellow light (595 nm, water-containing phase). When being exposed to an environment with 77% relative humidity, the emission color of the dehydrated phase was able to change from red to yellow within 20 s, and the red emission could be restored after reheating. The red to yellow emission switching could be achieved in acetone with water concentration as low as 0.2 vol%. The reversible PL transition phenomenon makes [H2BPZ][SbCl5]·H2O a potential material for luminescent water-sensing.
Journal Article
Molecular epidemiology of canine parvovirus type 2 in Vietnam from November 2016 to February 2018
by
Nga, Bui Thi To
,
Chiou, Ming-Tang
,
Lin, Wei-Hao
in
Biomedical and Life Sciences
,
Biomedicine
,
Canine parvovirus type 2
2019
Background
Canine parvovirus type 2 (CPV-2) was first identified in the late 1970s; it causes intestinal hemorrhage with severe bloody diarrhea in kennels and dog shelters worldwide. Since its emergence, CPV-2 has been replaced with new genetic variants (CPV-2a, CPV-2b, and CPV-2c). Currently, information about the genotype prevalence of CPV-2 in Vietnam is limited. In the present study, we investigated the genotype prevalence and distribution of CPV-2 in the three regions of Vietnam.
Methods
Rectal swabs were collected from 260 dogs with suspected CPV-2 infection from northern, central, and southern Vietnam from November 2016 to February 2018. All samples were identified as parvovirus positive by real-time PCR, and further genotyping was performed using a SimpleProbe® real-time PCR assay.
Results
Of the 260 Vietnamese CPV-2 isolates, 6 isolates (2.31%) were identified as CPV-2a, 251 isolates (96.54%) were identified as CPV-2c and 3 isolates (1.15%) were untypable using the SimpleProbe® real-time PCR assay. In northern Vietnam, the percentages of CPV-2a and CPV-2c were 2.97% (3/101) and 97.3% (98/101), respectively. In central Vietnam, the percentages of CPV-2a and CPV-2c were 1.11% (1/90) and 98.89% (89/90), respectively. In southern Vietnam, the percentages of CPV-2a and CPV-2c were 3.03% (2/66) and 96.97% (64/66), respectively. CPV-2b was not observed in this study. The VP2 genes of CPV-2c in Vietnam are more genetically similar to those of CPV-2c strains in China and Taiwan than to those of prototype CPV-2c strains (FJ222821) or the first Vietnamese CPV-2c (AB120727).
Conclusion
The present study provides evidence that CPV-2c is the most prevalent variant in Vietnam. Phylogenetic analysis demonstrated that the recent Vietnamese CPV-2c isolates share a common evolutionary origin with Asian CPV-2c strains.
Journal Article
Luminescence Enhancement and Temperature Sensing Properties of Hybrid Bismuth Halides Achieved via Tuning Organic Cations
2023
Bismuth-halide-based inorganic-organic hybrid materials (Bi-IOHMs) are desirable in luminescence-related applications due to their advantages such as low toxicity and chemical stability. Herein, two Bi-IOHMs of [Bpy][BiCl4(Phen)] (1, Bpy = N-butylpyridinium, Phen = 1,10-phenanthroline) and [PP14][BiCl4(Phen)]·0.25H2O (2, PP14 = N-butyl-N-methylpiperidinium), containing different ionic liquid cations and same anionic units, have been synthesized and characterized. Single-crystal X-ray diffraction reveals that compounds 1 and 2 crystallize in the monoclinic space group of P21/c and P21, respectively. They both possess zero-dimensional ionic structures and exhibit phosphorescence at room temperature upon excitation of UV light (375 nm for 1, 390 nm for 2), with microsecond lifetime (24.13 μs for 1 and 95.37 μs for 2). Hirshfeld surface analysis has been utilized to visually exhibit the different packing motifs and intermolecular interactions in 1 and 2. The variation in ionic liquids makes compound 2 have a more rigid supramolecular structure than 1, resulting in a significant enhancement in photoluminescence quantum yield (PLQY), that is, 0.68% for 1 and 33.24% for 2. In addition, the ratio of the emission intensities for compounds 1 and 2 shows a correlation with temperature. This work provides new insight into luminescence enhancement and temperature sensing applications involving Bi-IOHMs.
Journal Article
HMMR alleviates endoplasmic reticulum stress by promoting autophagolysosomal activity during endoplasmic reticulum stress‐driven hepatocellular carcinoma progression
The mechanism of hepatitis B virus (HBV)-induced carcinogenesis remains an area of interest. The accumulation of hepatitis B surface antigen in the endoplasmic reticulum (ER) of hepatocytes stimulates persistent ER stress. Activity of the unfolded protein response (UPR) pathway of ER stress may play an important role in inflammatory cancer transformation. How the protective UPR pathway is hijacked by cells as a tool for malignant transformation in HBV-related hepatocellular carcinoma (HCC) is still unclear. Here, we aimed to define the key molecule hyaluronan-mediated motility receptor (HMMR) in this process and explore its role under ER stress in HCC development.
An HBV-transgenic mouse model was used to characterize the pathological changes during the tumor progression. Proteomics and transcriptomics analyses were performed to identify the potential key molecule, screen the E3 ligase, and define the activation pathway. Quantitative real-time PCR and Western blotting were conducted to detect the expression of genes in tissues and cell lines. Luciferase reporter assay, chromatin immunoprecipitation, coimmunoprecipitation, immunoprecipitation, and immunofluorescence were employed to investigate the molecular mechanisms of HMMR under ER stress. Immunohistochemistry was used to clarify the expression patterns of HMMR and related molecules in human tissues.
We found sustained activation of ER stress in the HBV-transgenic mouse model of hepatitis-fibrosis-HCC. HMMR was transcribed by c/EBP homologous protein (CHOP) and degraded by tripartite motif containing 29 (TRIM29) after ubiquitination under ER stress, which caused the inconsistent expression of mRNA and protein. Dynamic expression of TRIM29 in the HCC progression regulated the dynamic expression of HMMR. HMMR could alleviate ER stress by increasing autophagic lysosome activity. The negative correlation between HMMR and ER stress, positive correlation between HMMR and autophagy, and negative correlation between ER stress and autophagy were verified in human tissues.
This study identified the complicated role of HMMR in autophagy and ER stress, that HMMR controls the intensity of ER stress by regulating autophagy in HCC progression, which could be a novel explanation for HBV-related carcinogenesis.
Journal Article
Posterior Reversible Encephalopathy Syndrome Induced by Mirtazapine Overdose: A Case Report
2025
Introduction: Posterior reversible encephalopathy syndrome (PRES) is a neurological emergency typically associated with hypertension or drug toxicity. Although mirtazapine is not a classical serotonergic agent, overdose may induce serotonin syndrome, which can contribute to PRES. Case Presentation: A 50‐year‐old woman presented with seizures, impaired consciousness, and autonomic instability following ingestion of > 300 mg mirtazapine. Magnetic resonance image (MRI) revealed vasogenic edema in the parieto‐occipital and frontal lobes. Her clinical features fulfilled the Hunter criteria for serotonin syndrome. Treatment with cyproheptadine led to full clinical and radiological recovery. Discussion: Serotonin syndrome may disrupt cerebral autoregulation and impair endothelial integrity, contributing to PRES. Although rare, similar cases have been reported with other serotonergic agents. This is the first reported case of mirtazapine overdose resulting in serotonin syndrome–associated PRES. Conclusion: Clinicians should recognize that mirtazapine overdose can cause serotonin syndrome and secondary PRES. Early identification and serotonin antagonism are crucial for recovery and prevention of sequelae.
Journal Article
Outbreak of Porcine Reproductive and Respiratory Syndrome Virus 1 in Taiwan
2020
Porcine reproductive and respiratory syndrome (PRRS) causes significant economic losses in the swine industry worldwide. The PRRS virus (PRRSV) can be divided into two species, PRRSV 1 (European) and PRRSV 2 (North American). In Taiwan, PRRSV 2 isolates are dominant and cause respiratory symptoms in nursing pigs. From October to November 2018, in a pig herd in central Taiwan, pregnant sows had abortions and stillbirths, and piglets suffered from respiratory disorders. Laboratory tests identified the presence of PRRSV 1 in serum from sows and suckling piglets in this scenario. The complete genome of the identified PRRSV 1 strain was genetically closely related to that of a European PRRSV vaccine strain (98.2%). This local European isolate is designated as PRRSV/NPUST-2789-3W-2/TW/2018 (NPUST2789). This report is the first to indicate an outbreak in Taiwan of a PRRSV 1 strain that shares a common evolutionary ancestor with the European PRRSV vaccine strain.
Journal Article
Common Spontaneous Tumors and Tumor-like Lesions in 70 Pet Rodents and Negative MMTV Detection in Mammary Tumors
2024
Compared to the number of studies on the neoplasms of laboratory rodents, fewer studies have focused on spontaneous neoplasms in pet rodents. Notably, the mouse mammary tumor virus (MMTV) is associated with mammary tumors in rodents. In this study, 77 tumors and tumor-like lesions of biopsy samples were collected from 70 pet rodents, including hamsters (n = 47), guinea pigs (n = 16), unknown species (n = 4), rats (n = 2), and a gerbil. Fifty tumors were collected from 47 hamsters, in which the most common tumors were mammary tumors (13/50), followed by fibrosarcoma (9/50), mast cell tumors (4/50), and squamous cell carcinoma (4/50). The collected subtypes of mammary tumors in hamsters included tubular carcinoma (n = 5), tubular adenoma (n = 4), carcinoma and malignant myoepithelioma (n = 1), simple tubular carcinoma (n = 1), adenosquamous carcinoma (n = 1), and tubulopapillary adenoma (n = 1). In addition, twenty tumors were collected from guinea pigs, in which the most common tumor was lipoma (6/20), followed by adenocarcinoma of the mammary gland (4/20), trichofolliculoma (2/20), and collagenous hamartomas (2/20). In guinea pigs, the subtypes of mammary gland tumors were tubular carcinoma (n = 2), tubular and solid carcinoma (n = 1), and tubulopapillary carcinoma (n = 1). In 20 cases of mammary tumors, MMTV was not detected, implicating no evidence of MMTV infection in mammary oncogenesis in pet rodents in Taiwan.
Journal Article
Comparative Efficacy of Horse and Chicken Serum for the In Vitro Cultivation of Mycoplasma hyorhinis Clinical Isolates
by
Chiou, Ming-Tang
,
Lin, Wei-Hao
,
Tseng, Yu-Wei
in
Animals
,
Bacteriological Techniques - methods
,
CCU (color changing unit)
2025
Mycoplasma hyorhinis is an important respiratory pathogen in swine, yet optimal culture conditions for high-yield propagation remain undefined. This study compared horse serum (HS) and chicken serum (CS) at graded concentrations (10%, 20%, 30%) for their ability to support in vitro growth of four clinical M. hyorhinis isolates (strains A, B, C, and D). Cultures were prepared in modified Friis medium, and growth performance was assessed by final titer (color changing unit, CCU/mL) and time-to-detection at 102 and 104 CCU/mL. All media supported growth, but HS consistently outperformed CS in both yield and growth kinetics. The highest titers (109 CCU/mL) and shortest detection times (3.6–6 days) were observed in 20% HS for most strains. Increasing HS concentration to 30% reduced yield for several strains, suggesting a concentration-dependent inhibitory effect. CS demonstrated limited but strain-dependent growth support, with comparable performance to HS for strain B at lower thresholds. These findings identify 20% HS as an optimal supplement for efficient M. hyorhinis cultivation, while highlighting the potential of CS as a cost-effective alternative under certain conditions, with implications for diagnostic reagent production and vaccine development.
Journal Article