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1.
Front Oncol ; 14: 1413273, 2024.
Article in English | MEDLINE | ID: mdl-38962272

ABSTRACT

Background: Angiogenesis plays a pivotal role in colorectal cancer (CRC), yet its underlying mechanisms demand further exploration. This study aimed to elucidate the significance of angiogenesis-related genes (ARGs) in CRC through comprehensive multi-omics analysis. Methods: CRC patients were categorized according to ARGs expression to form angiogenesis-related clusters (ARCs). We investigated the correlation between ARCs and patient survival, clinical features, consensus molecular subtypes (CMS), cancer stem cell (CSC) index, tumor microenvironment (TME), gene mutations, and response to immunotherapy. Utilizing three machine learning algorithms (LASSO, Xgboost, and Decision Tree), we screen key ARGs associated with ARCs, further validated in independent cohorts. A prognostic signature based on key ARGs was developed and analyzed at the scRNA-seq level. Validation of gene expression in external cohorts, clinical tissues, and blood samples was conducted via RT-PCR assay. Results: Two distinct ARC subtypes were identified and were significantly associated with patient survival, clinical features, CMS, CSC index, and TME, but not with gene mutations. Four genes (S100A4, COL3A1, TIMP1, and APP) were identified as key ARCs, capable of distinguishing ARC subtypes. The prognostic signature based on these genes effectively stratified patients into high- or low-risk categories. scRNA-seq analysis showed that these genes were predominantly expressed in immune cells rather than in cancer cells. Validation in two external cohorts and through clinical samples confirmed significant expression differences between CRC and controls. Conclusion: This study identified two ARG subtypes in CRC and highlighted four key genes associated with these subtypes, offering new insights into personalized CRC treatment strategies.

2.
Front Vet Sci ; 11: 1430113, 2024.
Article in English | MEDLINE | ID: mdl-38872801

ABSTRACT

N-glycosylation is a highly conserved glycan modification that plays crucial roles in various physiological processes, including protein folding, trafficking, and signal transduction. Porcine deltacoronavirus (PDCoV) poses a newly emerging threat to the global porcine industry. The spike protein of PDCoV exhibits a high level of N-glycosylation; however, its role in viral infection remains poorly understood. In this study, we applied a lentivirus-based entry reporter system to investigate the role of N-glycosylation on the viral spike protein during PDCoV entry stage. Our findings demonstrate that N-glycosylation at positions 652 and 661 of the viral spike protein significantly reduces the infectivity of PDCoV pseudotyped virus. Overall, our results unveil a novel function of N-glycosylation in PDCoV infection, highlighting its potential for facilitating the development of antiviral strategies.

3.
Front Cell Infect Microbiol ; 14: 1376725, 2024.
Article in English | MEDLINE | ID: mdl-38590440

ABSTRACT

In China, porcine reproductive and respiratory syndrome virus (PRRSV) vaccines are widely used. These vaccines, which contain inactivated and live attenuated vaccines (LAVs), are produced by MARC-145 cells derived from the monkey kidney cell line. However, some PRRSV strains in MARC-145 cells have a low yield. Here, we used two type 2 PRRSV strains (CH-1R and HuN4) to identify the genes responsible for virus yield in MARC-145 cells. Our findings indicate that the two viruses have different spread patterns, which ultimately determine their yield. By replacing the viral envelope genes with a reverse genetics system, we discovered that the minor envelope proteins, from GP2a to GP4, play a crucial role in determining the spread pattern and yield of type 2 PRRSV in MARC-145 cells. The cell-free transmission pattern of type 2 PRRSV appears to be more efficient than the cell-to-cell transmission pattern. Overall, these findings suggest that GP2a to GP4 contributes to the spread pattern and yield of type 2 PRRSV.


Subject(s)
Guanidines , Piperazines , Porcine Reproductive and Respiratory Syndrome , Porcine respiratory and reproductive syndrome virus , Vaccines , Swine , Animals , Porcine respiratory and reproductive syndrome virus/genetics , Cell Line
4.
World J Gastroenterol ; 29(34): 5075-5081, 2023 Sep 14.
Article in English | MEDLINE | ID: mdl-37753365

ABSTRACT

BACKGROUND: Primary biliary cholangitis (PBC) is a chronic progressive autoimmune cholestatic disease. The main target organ of PBC is the liver, and nonsuppurative inflammation of the small intrahepatic bile ducts may eventually develop into cirrhosis or liver fibrosis. AIM: To explore the clinical characteristics of early-stage PBC, identify PBC in the early clinical stage, and promptly treat and monitor PBC. METHODS: The data of 82 patients with PBC confirmed by pathology at Tianjin Second People's Hospital from January 2013 to November 2021 were collected, and the patients were divided into stage I, stage II, stage III, and stage IV according to the pathological stage. The general data, serum biochemistry, immunoglobulins, and autoimmune antibodies of patients in each stage were retrospectively analyzed. RESULTS: In early-stage (stages I + II) PBC patients, 50.0% of patients had normal alanine aminotransferase (ALT) levels, and 37.5% had normal aspartate aminotransferase (AST) levels. For the remaining patients, the ALT and AST levels were mildly elevated; all of these patients had levels of < 3 times the upper limit of normal values. The AST levels were significantly different among the three groups (stages I + II vs stage III vs stage IV, P < 0.05). In the early stage, 29.2% of patients had normal alkaline phosphatase (ALP) levels. The remaining patients had different degrees of ALP elevation; 6.3% had ALP levels > 5 times the upper limit of normal value. Moreover, γ-glutamyl transferase (GGT) was more robustly elevated, as 29.2% of patients had GGT levels of > 10 times the upper limit of normal value. The ALP values among the three groups were significantly different (P < 0.05). In early stage, the jaundice index did not increase significantly, but it gradually increased with disease progression. However, the above indicators were significantly different (P < 0.05) between the early-stage group and the stage IV group. With the progression of the disease, the levels of albumin and albumin/globulin ratio tended to decrease, and the difference among the three groups was statistically significant (P < 0.05). In early-stage patients, IgM and IgG levels as well as cholesterol levels were mildly elevated, but there were no significant differences among the three groups. Triglyceride levels were normal in the early-stage group, and the differences among the three groups were statistically significant (P < 0.05). The early detection rates of anti-mitochondria antibody (AMA) and AMA-M2 were 66.7% and 45.8%, respectively. The positive rate of anti-sp100 antibodies was significantly higher in patients with stage IV PBC. When AMA and AMA-M2 were negative, in the early stage, the highest autoantibody was anti-nuclear antibody (ANA) (92.3%), and in all ANA patterns, the highest was ANA centromere (38.5%). CONCLUSION: In early-stage PBC patients, ALT and AST levels are normal or mildly elevated, GGT and ALP levels are not elevated in parallel, GGT levels are more robustly elevated, and ALP levels are normal in some patients. When AMA and AMA-M2 are negative, ANA especially ANA centromere positivity suggests the possibility of early PBC. Therefore, in the clinic, significantly elevated GGT levels with or without normal ALP levels and with ANA (particularly ANA centromere) positivity (when AMA and AMA-M2 are negative) may indicate the possibility of early PBC.


Subject(s)
Autoimmune Diseases , Liver Cirrhosis, Biliary , Humans , Autoantibodies , Liver Cirrhosis, Biliary/diagnosis , Retrospective Studies , Albumins , Biomarkers
5.
Clin Res Hepatol Gastroenterol ; 46(8): 101957, 2022 10.
Article in English | MEDLINE | ID: mdl-35609821

ABSTRACT

BACKGROUND: The impact of hepatic steatosis on liver stiffness measurement (LSM) in both chronic hepatitis B(CHB) and metabolic-associated fatty liver disease (MAFLD) remains controversial. AIMS: To determine whether LSM is affected by hepatic steatosis in CHB-MAFLD. METHODS: Hepatic steatosis and liver fibrosis were assessed by histological and noninvasively methods. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the diagnostic performance of LSM. RESULTS: The prevalence of MAFLD in CHB patients (n = 436)was 47.5% (n = 207). For patients with low amounts of fibrosis (F0-1 and F0-2), the median LSM was 8.8 kPa and 9.2 kPa in patients with moderate- severe steatosis,which was significantly higher than that in patients with none-mild steatosis (P < 0.05) . The positive predictive value(PPV) was lower for LSM identifying significant fibrosis (F ≥ 2) as well as severe fibrosis (F ≥ 3) in group which controlled attenuation parameter(CAP) ≥ 268 dB/m than its counterpart(68.2% vs 84.6% and 24.3% vs 45.0%). The AUROC of LSM detected F ≥ 2 was 0.833 at a cutoff of 8.8 kPa and 0.873 at a cutoff of 7.0 kPa in patients with CAP ≥ 268 and CAP < 268, respectively. CONCLUSIONS: The presence of moderate-severe steatosis, detected by histology or CAP, should be taken into account to avoid overestimation of LSM.


Subject(s)
Elasticity Imaging Techniques , Fatty Liver , Hepatitis B, Chronic , Non-alcoholic Fatty Liver Disease , Biopsy , Elasticity Imaging Techniques/methods , Fatty Liver/complications , Hepatitis B, Chronic/complications , Hepatitis B, Chronic/pathology , Humans , Liver/diagnostic imaging , Liver/pathology , Liver Cirrhosis/complications , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/pathology , ROC Curve
6.
Am J Transl Res ; 14(2): 888-898, 2022.
Article in English | MEDLINE | ID: mdl-35273692

ABSTRACT

BACKGROUND: This study set out to explore the regulatory relationship between LINC00961/miR-3127 axis and non-small-cell lung carcinoma (NSCLC), so as to provide a new and effective molecular target for targeted therapy of NSCLC. METHODS: RNA-seq and miRNA-seq data of NSCLC and normal samples were obtained from The Cancer Genome Atlas (TCGA) database for analyzing LINC00961 and miR-3127 expression. Eighty-six pairs of clinical NSCLC tissues and adjacent normal tissues as well as NSCLC cell lines were obtained. Measurements of LINK00961 and miR-3127 levels were done using real-time-quantitative polymerase chain reaction (RT-qPCR). Furthermore, LINK00961 and miR-3127 in NSCLC cell were regulated respectively. The NSCLC cell proliferation, invasion and migration were determined with MTT assay, Transwell and wound healing assays, respectively. The levels of invasion- and apoptosis-related proteins were detected using western blots, and the connection of LINC00961 and miR-3127 was identified using dual luciferase reporter (DLR) assay. RESULTS: Differential analysis results of TCGA databases identified that LINC00961 was ubiquitously expressed at low levels in NSCLC, while miR-3127 was highly expressed. Similar expression trends of LINC00961 and miR-3127 were observed in clinical NSCLC samples and cell lines. Overexpression of LINC00961 and knockdown of miR-3127 significantly reduced NCI-H1299 cell migration, invasiveness, and multiplication, decreased MMP-2, MMP-9 and Bcl-2 protein levels, and increased E-cadherin, Bax and Caspase-3 protein levels. The DLR assay confirmed that miR-3127 can be targeted by LINC00961. CONCLUSION: LINC00961 functions as an anti-oncogene in NSCLC by modulating miR-3127.

7.
ACS Omega ; 7(4): 3758-3767, 2022 Feb 01.
Article in English | MEDLINE | ID: mdl-35128284

ABSTRACT

It is reported that the cis/trans conformation change of the peptide hormone oxytocin plays an important role in its receptors and activation and the cis conformation does not lead to antagonistic activity. Motivated by recent experiments and theories, the quasi-static amide-I 2D IR spectra of oxytocin are investigated using DFT/B3LYP (D3)/6-31G (d, p) in combination with the isotope labeling method under different electric fields. The theoretical amide-I IR spectra and bond length of the disulfide bond are consistent with the experimental values, which indicates that the theoretical modes are reasonable. Our theoretical results demonstrate that the oxytocin conformation is transformed from the cis conformation to the trans conformation with the change of the direction of the electric field, which is confirmed by the distance of the backbone carbonyl oxygen of Cys6 and Pro7, the Ramachandran plot of Cys6 and Pro7, the dihedral angle of Cß-S-S-Cß, and the rmsd of the oxytocin backbone. Moreover, the trans conformation as the result of the turn in the vicinity of Pro7 has a tighter secondary spatial structure than the cis conformation, including stronger hydrogen bonds, longer γ-turn geometry involving five amino acids, and a more stable disulfide bond. Our work provides new insights into the relationship between the conformation, the activation of the peptide hormone oxytocin, and the electric fields.

8.
Mol Biol Evol ; 39(2)2022 02 03.
Article in English | MEDLINE | ID: mdl-34893856

ABSTRACT

Domestic sheep and their wild relatives harbor substantial genetic variants that can form the backbone of molecular breeding, but their genome landscapes remain understudied. Here, we present a comprehensive genome resource for wild ovine species, landraces and improved breeds of domestic sheep, comprising high-coverage (∼16.10×) whole genomes of 810 samples from 7 wild species and 158 diverse domestic populations. We detected, in total, ∼121.2 million single nucleotide polymorphisms, ∼61 million of which are novel. Some display significant (P < 0.001) differences in frequency between wild and domestic species, or are private to continent-wide or individual sheep populations. Retained or introgressed wild gene variants in domestic populations have contributed to local adaptation, such as the variation in the HBB associated with plateau adaptation. We identified novel and previously reported targets of selection on morphological and agronomic traits such as stature, horn, tail configuration, and wool fineness. We explored the genetic basis of wool fineness and unveiled a novel mutation (chr25: T7,068,586C) in the 3'-UTR of IRF2BP2 as plausible causal variant for fleece fiber diameter. We reconstructed prehistorical migrations from the Near Eastern domestication center to South-and-Southeast Asia and found two main waves of migrations across the Eurasian Steppe and the Iranian Plateau in the Early and Late Bronze Ages. Our findings refine our understanding of genome variation as shaped by continental migrations, introgression, adaptation, and selection of sheep.


Subject(s)
Genome , Sheep, Domestic , Animals , Asia , Europe , Genetic Variation , Iran , Polymorphism, Single Nucleotide , Sequence Analysis, DNA , Sheep/genetics , Sheep, Domestic/genetics
9.
Curr Biol ; 30(20): 4085-4095.e6, 2020 10 19.
Article in English | MEDLINE | ID: mdl-32822607

ABSTRACT

The domestication and subsequent global dispersal of livestock are crucial events in human history, but the migratory episodes during the history of livestock remain poorly documented [1-3]. Here, we first developed a set of 493 novel ovine SNPs of the male-specific region of Y chromosome (MSY) by genome mapping. We then conducted a comprehensive genomic analysis of Y chromosome, mitochondrial DNA, and whole-genome sequence variations in a large number of 595 rams representing 118 domestic populations across the world. We detected four different paternal lineages of domestic sheep and resolved, at the global level, their paternal origins and differentiation. In Northern European breeds, several of which have retained primitive traits (e.g., a small body size and short or thin tails), and fat-tailed sheep, we found an overrepresentation of MSY lineages y-HC and y-HB, respectively. Using an approximate Bayesian computation approach, we reconstruct the demographic expansions associated with the segregation of primitive and fat-tailed phenotypes. These results together with archaeological evidence and historical data suggested the first expansion of early domestic hair sheep and the later expansion of fat-tailed sheep occurred ∼11,800-9,000 years BP and ∼5,300-1,700 years BP, respectively. These findings provide important insights into the history of migration and pastoralism of sheep across the Old World, which was associated with different breeding goals during the Neolithic agricultural revolution.


Subject(s)
DNA, Mitochondrial/genetics , Genome/genetics , Polymorphism, Single Nucleotide/genetics , Sheep, Domestic/genetics , Y Chromosome/genetics , Animals , Breeding , Cell Lineage/genetics , Chromosome Mapping , Genetic Variation/genetics , Male , Mitochondria/genetics , Phenotype , Phylogeny , Sheep , Sheep, Domestic/classification , Whole Genome Sequencing
10.
J Nematol ; 52: 1-2, 2020.
Article in English | MEDLINE | ID: mdl-32180387

ABSTRACT

During a survey of plant parasitic nematodes in 2019, at Gansu Province, China, the stunt nematode Tylenchorhynchus zeae was found parasitizing corn seedlings. Females, males and juveniles of T. zeae were observed on soil and roots samples of corn after processing and extraction. This population of stunt nematodes was identified based on morphological and by sequencing the ITS1 region of rDNA and D2/D3 fragments of the 28 S rRNA. The ITS1 and the D2/D3 sequences of this population, shared 99.00 to 99.05% and 99.43 to 99.73% of similarity with sequences corresponding to T. zeae in GenBank, respectively. This is the first report of T. zeae infecting corn in Gansu Province, northwest China.During a survey of plant parasitic nematodes in 2019, at Gansu Province, China, the stunt nematode Tylenchorhynchus zeae was found parasitizing corn seedlings. Females, males and juveniles of T. zeae were observed on soil and roots samples of corn after processing and extraction. This population of stunt nematodes was identified based on morphological and by sequencing the ITS1 region of rDNA and D2/D3 fragments of the 28 S rRNA. The ITS1 and the D2/D3 sequences of this population, shared 99.00 to 99.05% and 99.43 to 99.73% of similarity with sequences corresponding to T. zeae in GenBank, respectively. This is the first report of T. zeae infecting corn in Gansu Province, northwest China.

11.
J Asian Nat Prod Res ; 22(5): 452-463, 2020 May.
Article in English | MEDLINE | ID: mdl-31119952

ABSTRACT

The effects of coptisine against advanced stage of human pancreatic carcinoma PANC-1 cells was investigated in vitro. Coptisine (25-150 µM) treatment for 48 h caused dose-dependent cell growth inhibition by using CCK-8 assay. Additionally, coptisine was found to inhibit PANC-1 cells metastasis by the wound healing assay. Flow cytometry data indicated that coptisine (25-100 µM) exhibited dose-dependent G1 phase arrest and moderate reduction of S phase. Coptisine was also found to inhibit ERK phosphorylation and total ERK levels. Our research suggested that coptisine would be a potential therapeutic drug for the treatment of pancreatic cancer.


Subject(s)
Apoptosis , Pancreatic Neoplasms , Berberine/analogs & derivatives , Cell Line, Tumor , Cell Proliferation , Humans , Molecular Structure
12.
Emerg Microbes Infect ; 8(1): 1501-1510, 2019.
Article in English | MEDLINE | ID: mdl-31631782

ABSTRACT

As one of many nonstructural proteins of porcine reproductive and respiratory syndrome virus (PRRSV), nonstructural protein 12 (Nsp12) has received relatively little attention, and its role in virus replication, if any, is essentially unknown. By the application of reverse genetic manipulation of an infectious PRRSV clone, the current study is the first to demonstrate that Nsp12 is a key component of PRRSV replication. In addition, the biochemical properties of Nsp12 were evaluated, revealing that Nsp12 forms dimers when exposed to oxidative conditions. Furthermore, we systemically analyzed the function of Nsp12 in PRRSV RNA synthesis using a strand-specific PCR method. To our surprise, Nsp12 was not found to be involved in minus-strand genomic RNA (-gRNA) synthesis; importantly, our results indicate that Nsp12 is involved in the synthesis of both plus- and minus-strand subgenomic mRNAs (+sgmRNA and -sgmRNA). Finally, we found that the combination of cysteine 35 and cysteine 79 in Nsp12 is required for sgmRNA synthesis. To our knowledge, we are the first to report the biological role of Nsp12 in the PRRSV lifecycle, and we conclude that Nsp12 is involved in the synthesis of both + sgRNA and -sgRNA.


Subject(s)
Gene Expression Regulation, Viral , Porcine respiratory and reproductive syndrome virus/metabolism , RNA, Messenger/genetics , RNA, Viral/genetics , Viral Nonstructural Proteins/metabolism , Animals , Open Reading Frames , Porcine Reproductive and Respiratory Syndrome/virology , Porcine respiratory and reproductive syndrome virus/genetics , RNA, Messenger/metabolism , RNA, Viral/metabolism , Swine , Transcription, Genetic , Viral Nonstructural Proteins/genetics , Virus Replication
13.
Aliment Pharmacol Ther ; 50(1): 93-102, 2019 07.
Article in English | MEDLINE | ID: mdl-31094016

ABSTRACT

BACKGROUND: Liver stiffness measurement (LSM) by transient elastography is a noninvasive method for the diagnosis of hepatic fibrosis. The impact of hepatic steatosis on LSM remains to be explored. AIM: To determine whether LSM is affected by hepatic steatosis in patients with chronic hepatitis B (CHB). METHODS: Consecutive patients with biopsy-proven CHB were prospectively enrolled. Hepatic steatosis was classified by pathology as none (S0, <5%), mild (S1, 5%-33%), and moderate-severe (S2-3, >33%), and quantitatively by controlled attenuation parameter (CAP) as CAP S0 (≤247 dB/m), CAP S1 (248-267 dB/m) and CAP S2-3 (≥268 dB/m). Liver fibrosis was assessed by METAVIR classification and noninvasively by LSM. RESULTS: The prevalence of non-alcoholic fatty liver disease (n = 223) in CHB patients (n = 593) was 37.6%. Forty-eight belonged to S2-3 and 127 belonged to CAP S2-3. In patients without significant fibrosis (F0-1), the median LSM (kPa) was 7.4 in S2-3 and 7.1 in CAP S2-3, which was significantly higher than that in S0/S1 (P = 0.005) and CAP S0/S1 (P = 0.003). No significant difference was found in significant fibrosis (F2-4). For LSM identifying significant fibrosis (F2-4), the negative predictive value was higher in CHB patients with CAP ≥ 268 compared to those with CAP < 268 (0.81 vs 0.73); the positive predictive value was lower in CAP ≥ 268 than its counterpart (0.65 vs 0.76). CONCLUSIONS: Moderate-severe steatosis increased the LSM value in CHB patients without significant fibrosis. A CAP ≥ 268 did not affect LSM for ruling out, but it slightly affected LSM for ruling in significant fibrosis. TRIAL REGISTRATION: ChiCTR-DDT-13003983.


Subject(s)
Hepatitis B, Chronic/pathology , Liver Cirrhosis/pathology , Non-alcoholic Fatty Liver Disease/pathology , Adult , Biopsy , Elasticity Imaging Techniques , Female , Hepatitis B, Chronic/diagnostic imaging , Humans , Liver/pathology , Liver Cirrhosis/diagnostic imaging , Male , Middle Aged , Non-alcoholic Fatty Liver Disease/diagnostic imaging
14.
Mol Biol Evol ; 36(2): 283-303, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30445533

ABSTRACT

Tibetan sheep are the most common and widespread domesticated animals on the Qinghai-Tibetan Plateau (QTP) and have played an essential role in the permanent human occupation of this high-altitude region. However, the precise timing, route, and process of sheep pastoralism in the QTP region remain poorly established, and little is known about the underlying genomic changes that occurred during the process. Here, we investigate the genomic variation in Tibetan sheep using whole-genome sequences, single nucleotide polymorphism arrays, mitochondrial DNA, and Y-chromosomal variants in 986 samples throughout their distribution range. We detect strong signatures of selection in genes involved in the hypoxia and ultraviolet signaling pathways (e.g., HIF-1 pathway and HBB and MITF genes) and in genes associated with morphological traits such as horn size and shape (e.g., RXFP2). We identify clear signals of argali (Ovis ammon) introgression into sympatric Tibetan sheep, covering 5.23-5.79% of their genomes. The introgressed genomic regions are enriched in genes related to oxygen transportation system, sensory perception, and morphological phenotypes, in particular the genes HBB and RXFP2 with strong signs of adaptive introgression. The spatial distribution of genomic diversity and demographic reconstruction of the history of Tibetan sheep show a stepwise pattern of colonization with their initial spread onto the QTP from its northeastern part ∼3,100 years ago, followed by further southwest expansion to the central QTP ∼1,300 years ago. Together with archeological evidence, the date and route reveal the history of human expansions on the QTP by the Tang-Bo Ancient Road during the late Holocene. Our findings contribute to a depth understanding of early pastoralism and the local adaptation of Tibetan sheep as well as the late-Holocene human occupation of the QTP.


Subject(s)
Acclimatization/genetics , Genome , Human Migration , Hybridization, Genetic , Sheep/genetics , Altitude , Animals , Ecotype , Humans , Selection, Genetic , Tibet
15.
Biomed Pharmacother ; 108: 925-933, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30372904

ABSTRACT

Isorhamnetin, a flavonoid ingredient derived from Vernonia anthelmintica (L.) Willd., has shown a spectrum of antitumor activity. However, the chemopreventive potential of isorhamnetin on advanced pancreatic cancer and the underlying molecular mechanism remain unknown. In the current study, treatment of the advanced pancreatic adenocarcinoma cell line PANC-1 with isorhamnetin resulted in robust cell growth arrest. PI-annexin V double staining and Hoechst 33258 staining revealed that isorhamnetin moderately induced early apoptosis without morphological alterations of nuclei. Instead, isorhamnetin caused cell cycle S-phase arrest through downregulation of cyclin A. In addition, isorhamnetin decreased the phosphorylation levels of MEK and ERK in the Ras/MAPK pathway, which is involved in regulating cell proliferation, differentiation and apoptosis. Wound-healing experiments demonstrated isorhamnetin significantly reduced the migratory behavior of PANC-1 cells. Altogether, the present study suggests that isorhamnetin may be a potential agent for prevention of pancreatic carcinoma.


Subject(s)
Cell Cycle Checkpoints/drug effects , Cell Proliferation/drug effects , Pancreatic Neoplasms/drug therapy , Quercetin/analogs & derivatives , S Phase/drug effects , Apoptosis/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Down-Regulation/drug effects , Humans , Phosphorylation/drug effects , Quercetin/pharmacology , Signal Transduction/drug effects , Pancreatic Neoplasms
16.
Oncotarget ; 9(15): 12174-12185, 2018 Feb 23.
Article in English | MEDLINE | ID: mdl-29552301

ABSTRACT

Porcine reproductive and respiratory syndrome virus (PRRSV) is a problematic virus that is difficult to control. The principal target cells for PRRSV infection are porcine alveolar macrophages (PAMs). Increasing evidence has demonstrated that CD163 is the determinant receptor for PRRSV infection. However, the relationship between CD163 abundance and PRRSV infection is unclear. In this study, we first generated primary immortalized PAMs (iPAMs) using SV40 large T antigen and demonstrated that CD163 expression is suppressed by the alternative splicing of mRNA in iPAMs. Two forms of CD163 transcripts were discovered, and most iPAMs expressed a short-form CD163 transcript that lacked from scavenger receptor cysteine-rich tandem repeat 1 (SRCR1) to SRCR5 of the functional domain. More importantly, using flow cytometric cell sorting technology, we isolated CD163-positive single-cell-derived clones with varying CD163 abundances to investigate the relationship between CD163 abundance and PRRSV infection. For the first time, we showed that cells with low CD163 abundance (approximately 20%) do not initiate PRRSV infection, while cells with moderate CD163 abundance display limited infection. PRRSV initiated efficient infection only in cells with high CD163 abundances. Our results demonstrate that CD163 abundance is a pivotal switch for PRRSV replication.

17.
Arch Virol ; 163(5): 1263-1270, 2018 May.
Article in English | MEDLINE | ID: mdl-29411137

ABSTRACT

Porcine reproductive and respiratory syndrome virus (PRRSV) is a pathogen of great economic significance that impacts the swine industry globally. Since the first report of a porcine reproductive and respiratory syndrome (PRRS) outbreak, tremendous efforts to control this disease, including various national policies and plans incorporating the use of multiple modified live-virus vaccines, have been made. However, PRRSV is still a significant threat to the swine industry, and new variants continually emerge as a result of PRRSV evolution. Several studies have shown that pandemic PRRSV strains have enormous genetic diversity and that commercial vaccines can only provide partial protection against these strains. Therefore, effective anti-PRRSV drugs may be more suitable and reliable for PRRSV control. In this study, we observed that isobavachalcone (IBC), which was first isolated from Psoralea corylifolia, had potent anti-PRRSV activity in vitro. Although many biological activities of IBC have been reported, this is the first report describing the antiviral activity of IBC. Furthermore, after a systematic investigation, we demonstrated that IBC inhibits PRRSV replication at the post-entry stage of PRRSV infection. Thus, IBC may be a candidate for further evaluation as a therapeutic agent against PRRSV infection of swine in vivo.


Subject(s)
Antiviral Agents/pharmacology , Chalcones/pharmacology , Porcine respiratory and reproductive syndrome virus/drug effects , Virus Replication/drug effects , Animals , Drug Discovery , Inhibitory Concentration 50 , Macrophages, Alveolar/virology , Porcine Reproductive and Respiratory Syndrome/drug therapy , Porcine Reproductive and Respiratory Syndrome/virology , Porcine respiratory and reproductive syndrome virus/physiology , Swine , Virus Internalization
18.
Zhongguo Zhong Yao Za Zhi ; 42(20): 3932-3937, 2017 Oct.
Article in Chinese | MEDLINE | ID: mdl-29243430

ABSTRACT

Components that systematic separated from the root of Anaycclus pyrethrum were identified, in order to lay a foundation for future study of the root of A. pyrethrum. The CCK-8 assay showed that dichloromethane fraction exhibited the highest degree of cytotoxicity than others. Ten monomeric components were obtained from dichloromethane fraction and ethyl acetate fraction extracted from the root of A. pyrethrum, including 7 N-alkylamides, one coumarin and two flavonoid glycosides. They were identified as tetradeca-2E,4E,8E-trienoic acid 4-hydroxyphenylethylamide(1), deca-2E,4E-dienoicacid isobutylamide(2), undeca-2E,4E-diene-8,10-diynoic acid phenylethylamide(3), tetradeca-2E,4E-dienoic acid 4-hydroxyphenylethylamide(4), tetradeca-2E,4E-diene-8,10-diynoic acid isobutylamide(5), deca-2E,4E- dienoic acid 4-hydroxyphenylethylamide(6), dodeca-2E,4E-dienoic acid 4-hydroxy -phenyl-ethylamide(7), isoscopoletin(8), quercetin-7-O-ß-D-glucopyranoside(9), isorhamnetin-7-O-ß-D-glucopyranoside(10). Among them, compound 1 was identified as a new compound, Compounds 2-4, 8-10 were isolated from this herb for the first time.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Asteraceae/chemistry , Plant Extracts/pharmacology , Plant Roots/chemistry , Amides/chemistry , Antineoplastic Agents, Phytogenic/chemistry , Cell Line, Tumor , Coumarins/chemistry , Flavonoids/chemistry , Glycosides/chemistry , Humans , Plant Extracts/chemistry
19.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 48(2): 221-224, 2017 Mar.
Article in Chinese | MEDLINE | ID: mdl-28612530

ABSTRACT

OBJECTIVES: To investigate whether minocycline could inhibit neuroinflammation induced by microglia activation through suppression of adenosine A2Areceptor (A2AR)expression in rats after cerebral ischemia/reperfusion (I/R) injury. METHODS: Thirty male Sprageue-Dawley rats were randomly divided into 3 groups: sham group, I/R group and minocycline group. The rats were subjected to occlusion of the right middle cerebral artery (MCAO) for 2 h to establish stroke I/R model, and 3 mg/kg minocycline was injected intravenously immediately after reperfusion twice a day in minocycline group. At 24 h after I/R, the inflammatory cytokines IL-1ß and IL-6 in peri-infarct region were measured by Western blot, microglia activation was detected by double-immunofluorescence labeling. A2AR density was detected by immunohistofluorescence and Western blot. RESULTS: The number of CD11b-positive cells in I/R group was increased when compared with that in sham group. The expressions of IL-1ß, IL-6 and A2AR were markedly up-regulated after I/R. Minocycline significantly decreased the expressions of IL-1ß, IL-6 and A2AR and the number of CD11b-positive cells in peri-infarct region. CONCLUSION: Minocycline could prevent cerebral ischemia induced neuroinflammation by the suppression of microglial activation, which may be related to down-regulation of A2AR expression.


Subject(s)
Adenosine A2 Receptor Antagonists/pharmacology , Brain Ischemia/drug therapy , Microglia/drug effects , Minocycline/pharmacology , Reperfusion Injury/drug therapy , Stroke/drug therapy , Animals , CD11b Antigen/metabolism , Interleukin-1beta/metabolism , Interleukin-6/metabolism , Male , Rats , Rats, Sprague-Dawley , Receptor, Adenosine A2A
20.
Arch Virol ; 162(9): 2715-2726, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28578523

ABSTRACT

Porcine circovirus type 2 (PCV2) is the cause of postweaning multisystemic wasting syndrome (PMWS), which encompasses several distinct symptoms in pigs. PCV2 infection and clinical incidence of PMWS have increased in recent years, possibly due to shifts in viral populations and mutations. In this study, we identified PVC2 strains currently afflicting pig populations in mainland China, because this is a prerequisite for developing a specific vaccine to control the spread of PMWS. We collected 235 tissue samples from 16 provinces between 2014 and 2016. Of these, 152 samples were positive for PCV2. We compared the sequences we obtained for the PVC2 capsid gene, ORF2, to those of the Chinese PCV2 sequences deposited in GenBank between 2002 and 2016 (n = 648). Phylogenetic analyses demonstrated that the PCV2d genotype was the most prevalent strain in the sample population included in GenBank and among the positive samples from this study. We also found one PCV2c strain among the GenBank sequences. Furthermore, PCV2a-2F was the predominant genotype in the PCV2a cluster. Amino acid sequence comparisons demonstrated 70.8-100% identity within PCV ORF2 and several consistent mutations in ORF2. More interestingly, six isolates were classified as recombinant strains. Cumulatively, this study represents the first comprehensive description of PCV2 strains distribution, including recent samples, in Chinese porcine populations. We demonstrate the existence of high genetic variability among PVC2 strains and the ability of this virus to rapidly evolve.


Subject(s)
Circovirus/genetics , Porcine Postweaning Multisystemic Wasting Syndrome/virology , Swine Diseases/virology , Animals , China/epidemiology , Genetic Variation , Genotype , Mutation , Phylogeny , Porcine Postweaning Multisystemic Wasting Syndrome/epidemiology , Recombination, Genetic , Swine , Swine Diseases/epidemiology
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