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1.
J Med Virol ; 96(1): e29323, 2024 01.
Article in English | MEDLINE | ID: mdl-38164047

ABSTRACT

Enteroviruses (EVs), single-stranded, positive-sense RNA viruses, can be classified into four species (A-D), which have previously been linked to a diverse range of disease manifestations and infections affecting the central nervous system. In the Enterovirus species B (EV-B), Echovirus type 11 (E11) has been observed to occasionally circulate in Taiwan, which was responsible for an epidemic of enterovirus infections in 2018. Here, 48 clinical specimens isolated in 2003, 2004, 2009, and 2018 were collected for the high-throughput sequencing. Notably, we identified 2018 Taiwanese strains having potential recombinations in the 3D gene, as well as one 2003 strain having a double recombination with E6 and Coxsackievirus B5 in the P2 and P3 regions, respectively. Additionally, one amino acid signature mutated from the Histidine (H) in throat swab specimens to the Tyrosine (Y) in cerebral spinal fluid specimens was detected at position 1496 (or 57) of the genomic coordinate (or 3A gene) to further demonstrate intra-host evolution in different organs. In conclusion, this study identifies potential intertypic recombination events and an intra-host signature mutation in E11 strains, isolated during a 2018 neurological disease outbreak in Taiwan, contributing to our understanding of its evolution and pathogenesis.


Subject(s)
Enterovirus Infections , Enterovirus , Humans , Phylogeny , Enterovirus B, Human/genetics , Enterovirus/genetics , Enterovirus Infections/epidemiology , Recombination, Genetic
2.
Semin Cancer Biol ; 83: 253-260, 2022 08.
Article in English | MEDLINE | ID: mdl-33785446

ABSTRACT

Thyroid cancer is the most common primary endocrine malignancy with papillary thyroid carcinoma (PTC) its most common subtype. The jump in diagnoses over last many years has prompted re-assessment of molecularly targeted therapies and the discovery of novel targets. Long non-coding RNAs (lncRNAs) are increasingly being assessed for their expression in various PTC models. Interestingly, in addition to cell line models, a large proportion of the reported studies have evaluated lncRNA levels in PTC patient samples providing an immediate clinical relevance of their findings. While most lncRNAs either promote or suppress PTC pathogenesis, data on individual lncRNAs is not very clear. As expected, lncRNAs function in PTC through sponging of microRNAs as well as modulation of several signaling pathways. The process of epithelial-mesenchymal transition and the PI3K/Akt and wnt signaling pathways have emerged as the primary targets of lncRNAs in PTC. This comprehensive review discusses all the information that is available on lncRNAs in PTC, ranging from in vitro and in vivo findings to the possible role of lncRNAs as diagnostic and/or prognostic biomarkers.


Subject(s)
MicroRNAs , RNA, Long Noncoding , Thyroid Neoplasms , Cell Line, Tumor , Cell Proliferation/genetics , Epigenesis, Genetic , Gene Expression Regulation, Neoplastic , Humans , MicroRNAs/genetics , Phosphatidylinositol 3-Kinases/metabolism , RNA, Long Noncoding/genetics , Thyroid Cancer, Papillary/genetics , Thyroid Cancer, Papillary/metabolism , Thyroid Cancer, Papillary/pathology , Thyroid Neoplasms/genetics , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathology
3.
PLoS Pathog ; 16(9): e1008857, 2020 09.
Article in English | MEDLINE | ID: mdl-32936838

ABSTRACT

An outbreak of the hand-foot-mouth disease with severe neurological cases, mainly caused by the genotype C1 enterovirus A71 (EV-A71), occurred in Taiwan between 2018 and early 2019. In the recent decade, the most dominant EV-A71 genotypes in Taiwan were B5 and C4 but changed to C1 in 2018. Antibody-mediated immunity plays a key role in limiting the EV-A71 illness in humans. However, the level of neutralizing activities against genotype C1 virus by human polyclonal and monoclonal antibodies (MAbs) remains largely unclear. In the study, we demonstrated that that 39% (9 in 23) of post-infection sera from the genotype B5- or C4-infected patients in 2014-2017 exhibit reduced titers with the 2018-2019 genotype C1 viruses than with the earlier B5 and C4 viruses tested. This finding with polyclonal sera is confirmed with human MAbs derived from genotype B5 virus-infected individuals. The 2018-2019 genotype C1 virus is resistant to the majority of canyon-targeting human MAbs, which may be associated with the residue change near or at the bottom of the canyon region on the viral capsid. The remaining three antibodies (16-2-11B, 16-3-4D, and 17-1-12A), which target VP1 S241 on the 5-fold vertex, VP3 E81 on the 3-fold plateau and VP2 D84 on the 2-fold plateau of genotype C1 viral capsid, respectively, retained neutralizing activities with variable potencies. These neutralizing antibodies were also found to be protective against a lethal challenge of the 2018-2019 genotype C1 virus in an hSCARB2-transgenic mice model. These results indicate that the EV-A71-specific antibody response may consist of a fraction of poorly neutralizing antibodies against 2018-2019 genotype C1 viruses among a subset of previously infected individuals. Epitope mapping of protective antibodies that recognize the emerging genotype C1 virus has implications for anti-EV-A71 MAbs and the vaccine field.


Subject(s)
Antigens, Viral/genetics , Enterovirus A, Human/genetics , Genetic Variation , Genome, Viral , Genotype , Hand, Foot and Mouth Disease/genetics , Animals , Antibodies, Neutralizing/genetics , Antibodies, Neutralizing/immunology , Antibodies, Viral/genetics , Antibodies, Viral/immunology , Antigens, Viral/immunology , Child , Child, Preschool , Enterovirus A, Human/immunology , Enterovirus A, Human/isolation & purification , Female , Hand, Foot and Mouth Disease/epidemiology , Hand, Foot and Mouth Disease/immunology , Humans , Male , Mice , Mice, Transgenic , Taiwan
4.
Dig Dis Sci ; 67(3): 936-946, 2022 03.
Article in English | MEDLINE | ID: mdl-33782806

ABSTRACT

OBJECTIVE: To explore how lncRNA SNHG14 modulates the biological features of hepatocellular carcinoma (HCC) cells by regulating SOX9 via mediating miR-206. METHODS: HCC tissues were collected to perform the quantitative reverse transcriptase polymerase chain reaction to determine the expressions of SNHG14, miR-206, and SOX9. HCC cell line SMCC7721 was selected for co-transfection by si-SNHG14/miR-206 inhibitor/si-SOX9, followed by the measurement of cell proliferation using Cell Count Kit-8 (CCK-8) assay and clone formation assay. The migration and invasion were evaluated by wound healing test and Transwell assay. The apoptotic rate was determined by flow cytometry. Levels of the apoptosis-related proteins were measured through Western blotting. RESULTS: SNHG14 and SOX9 were up-regulated in HCC tumor tissues compared with adjacent normal tissues, with decreased miR-206 expression. Moreover, SNHG14 expression was significantly associated with the TNM stage, lymphatic metastasis, and histological differentiation of HCC patients. Besides, inverse correlations between SNHG14 and miR-206, as well as between miR-206 and SOX9, were noted. The dual luciferase reporter gene assay, RIP, and RNA pull-down experiments also revealed the targeting relationship between SNHG14 and miR-206 or between miR-206 and SOX9. Silencing SNHG14 and SOX9 inhibited the proliferation, invasion, and migration of HCC cells, with increased apoptosis, which was all abolished by silencing miR-206. CONCLUSION: Inhibition of SNHG14 suppresses SOX9 by up-regulating miR-206, to further inhibit the proliferation, migration, and invasion of HCC cells with the promoted apoptosis, which is a novel target for the treatment of HCC.


Subject(s)
Carcinoma, Hepatocellular , Liver Neoplasms , MicroRNAs , RNA, Long Noncoding , Apoptosis , Carcinoma, Hepatocellular/pathology , Cell Line , Cell Line, Tumor , Cell Movement , Cell Proliferation , Gene Expression Regulation, Neoplastic , Humans , Liver Neoplasms/pathology , MicroRNAs/genetics , MicroRNAs/metabolism , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , SOX9 Transcription Factor/genetics , SOX9 Transcription Factor/metabolism
5.
J Clin Microbiol ; 58(8)2020 07 23.
Article in English | MEDLINE | ID: mdl-32518072

ABSTRACT

Real-time reverse transcription-PCR (RT-PCR) is currently the most sensitive method to detect severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes coronavirus disease 2019 (COVID-19). However, the correlation between detectable viral RNA and culturable virus in clinical specimens remains unclear. Here, we performed virus culture for 60 specimens that were confirmed to be positive for SARS-CoV-2 RNA by real-time RT-PCR. The virus could be successfully isolated from 12 throat and nine nasopharyngeal swabs and two sputum specimens. The lowest copy number required for virus isolation was determined to be 5.4, 6.0, and 5.7 log10 genome copies/ml sample for detecting the nsp12, E, and N genes, respectively. We further examined the correlation of genome copy number and virus isolation in different regions of the viral genome, demonstrating that culturable specimens are characterized by high copy numbers with a linear correlation observed between copy numbers of amplicons targeting structural and nonstructural regions. Overall, these results indicate that in addition to the copy number, the integrity of the viral genome should be considered when evaluating the infectivity of clinical SARS-CoV-2 specimens.


Subject(s)
Betacoronavirus/growth & development , Betacoronavirus/isolation & purification , Clinical Laboratory Techniques/methods , Coronavirus Infections/diagnosis , Coronavirus Infections/virology , Pneumonia, Viral/diagnosis , Pneumonia, Viral/virology , Virus Cultivation/methods , Betacoronavirus/genetics , COVID-19 , COVID-19 Testing , COVID-19 Vaccines , Correlation of Data , Humans , Nasopharynx/virology , Pandemics , Pharynx/virology , Real-Time Polymerase Chain Reaction/methods , Reverse Transcriptase Polymerase Chain Reaction/methods , SARS-CoV-2
6.
J Gen Virol ; 100(5): 752-759, 2019 05.
Article in English | MEDLINE | ID: mdl-30994443

ABSTRACT

Influenza A virus mutates rapidly, allowing it to escape natural and vaccine-induced immunity. Neuraminidase (NA) is a surface protein capable of cleaving the glycosidic linkages of neuraminic acids to release newly formed virions from infected cells. Genetic variants within a viral population can influence the emergence of pandemic viruses as well as drug susceptibility and vaccine effectiveness. In the present study, 55 clinical specimens from patients infected with the 2009 pandemic influenza A/H1N1 virus, abbreviated as A(H1N1)pdm09, during the 2015-2016 outbreak season in Taiwan were collected. Whole genomes were obtained through next-generation sequencing. Based on the published sequences from A(H1N1)pdm09 strains worldwide, a mixed population of two distinct variants at NA position 151 was revealed. We initially reasoned that such a mixed population may have emerged during cell culture. However, additional investigations confirmed that these mixed variants were detectable in the specimens of patients. To further investigate the role of the two NA-151 variants in a dynamic population, a reverse genetics system was employed to generate recombinant A(H1N1)pdm09 viruses. It was observed that the mixture of the two distinct variants was characterized by a higher replication rate compared to the recombinant viruses harbouring a single variant. Moreover, an NA inhibition assay revealed that a high frequency of the minor NA-151 variant in A(H1N1)pdm09 was associated with a reduced susceptibility to NA inhibitors. We conclude that two distinct NA-151 variants can be identified in patient specimens and that such variants may increase viral replication and NA activity.


Subject(s)
Influenza A Virus, H1N1 Subtype/genetics , Neuraminidase/genetics , Viral Proteins/genetics , Animals , Cell Line , Dogs , Genetic Variation/genetics , HEK293 Cells , Humans , Influenza, Human/virology , Madin Darby Canine Kidney Cells , Orthomyxoviridae Infections/virology , Population Dynamics , Virus Replication/genetics
7.
Chemotherapy ; 64(1): 42-47, 2019.
Article in English | MEDLINE | ID: mdl-31163446

ABSTRACT

OBJECTIVES: We aimed to identify an optimal regimen for low-risk gestational trophoblastic neoplasia (LR-GTN) providing reduction in dosage and toxicity/side effects, enhancement of therapeutic efficacy, and a shorter treatment duration. METHODS: A total of 149 LR-GTN patients were enrolled in the affiliated Beijing Maternity Hospital of Capital Medical University from January 2014 to January 2017 and randomly divided into 3 groups with 50 cases in the methotrexate (MTX) group, 49 in actinomycin D (ACT-D) group, and 50 in ACT-D+MTX group. Follow-up recorded symptoms, physical and bimanual gynecological examinations, routine blood test, serum ß-HCG level, liver and renal functions, electrolytes, electrocardiogram before each treatment course, and pelvic and abdominal B-mode ultrasound or pelvic/abdominal/chest computed tomography. RESULTS: Serum complete remission (SCR) was 96.0, 87.8, and 83.7% for the ACT-D+MTX, ACT-D, and MTX groups, respectively, with SCR being highest in the ACT-D+MTX group, statistically higher than in the MTX group. Vomiting was the only side effect differing significantly by chemotherapy regimen, with a distinctly higher incidence in the ACT-D+MTX group compared with the MTX group (p = 0.028). The reduction rate of serum ß-HCG in the ACT-D+MTX group was significantly greater than in the other 2 groups. CONCLUSION: Combined ACT-D+MTX chemotherapy achieved overall better efficacy and showed less toxicity than ACT-D or MTX alone, and thus can be prioritized for the treatment of LR-GTN.


Subject(s)
Antimetabolites, Antineoplastic/therapeutic use , Dactinomycin/therapeutic use , Gestational Trophoblastic Disease/drug therapy , Methotrexate/therapeutic use , Adult , Antimetabolites, Antineoplastic/adverse effects , Chorionic Gonadotropin/blood , Dactinomycin/adverse effects , Drug Therapy, Combination , Female , Gestational Trophoblastic Disease/pathology , Hematologic Diseases/etiology , Humans , Logistic Models , Methotrexate/adverse effects , Middle Aged , Neoplasm Staging , Oral Ulcer/etiology , Pregnancy , Prognosis , Treatment Outcome , Young Adult
8.
Microb Pathog ; 118: 357-360, 2018 May.
Article in English | MEDLINE | ID: mdl-29578061

ABSTRACT

The current study was designed and performed to investigate the effect of mefloquine on the proliferation and tumor formation potential of liver cancer stem cells. CD133 + HepG2 cells were identified using MACS and showed markedly higher tumor formation potential compared to the parental cells. The secondary tumors formed by CD133 + cells were markedly large in size and more in number compared to the parental cells. Mefloquine treatment of CD133 + HepG2 cells inhibited the proliferation selectively in concentration based manner. The rate of proliferation was inhibited to 82 and 12% in parental and CD133 + sphere forming cells, respectively on treatment with 10 µM concentration of mefloquine. The number of secondary tumors formed by primary tumors was decreased significantly on treatment with 10 µM mefloquine concentration. Treatment of the liver cancer stem cells with mefloquine markedly decreased the potential to undergo self-renewal at 10 µM concentration after 48 h. The results from western blot analysis showed significantly higher expression of cancer stem cell molecules ß-catenin and cyclin D1 in LCSCs. Treatment of the LCSCs with various concentrations of mefloquine reduced the expression levels of ß-catenin and cyclin D1. Administration of the CD133 + cell tumor xenografts in the mice led to the formation of large sized tumors in the control group. However, the tumor growth was inhibited significantly in the mice on treatment with 10 mg/kg doses of mefloquine after day 21. The tumor weight was significantly lower in the animals of mefloquine treatment group compared to the control group. Thus, mefloquine treatment inhibits self-renewal and proliferation potential of cells through targeting ß-catenin pathway.


Subject(s)
Carcinoma, Hepatocellular/drug therapy , Liver Neoplasms/drug therapy , Mefloquine/pharmacology , beta Catenin/drug effects , beta Catenin/metabolism , AC133 Antigen , Animals , Cell Proliferation/drug effects , Cell Survival/drug effects , Cyclin D1/drug effects , Cyclin D1/metabolism , Disease Models, Animal , Drug Combinations , Hep G2 Cells/drug effects , Humans , Lithium Chloride , Male , Mefloquine/administration & dosage , Mice , Mice, Inbred BALB C , Neoplastic Stem Cells/drug effects , Transplantation, Heterologous
9.
Arch Virol ; 162(7): 2003-2012, 2017 Jul.
Article in English | MEDLINE | ID: mdl-28424887

ABSTRACT

Metagenomic approaches to detect viral genomes and variants in clinical samples have various challenges, including low viral titers and bacterial and human genome contamination. To address these limitations, we examined a next-generation sequencing (NGS) and iterative mapping approach for virus detection in clinical samples. We analyzed 40 clinical specimens from hospitalized children diagnosed with acute bronchiolitis, croup, or respiratory tract infections in which virus identification by viral culture or polymerase chain reaction (PCR) was unsuccessful. For our NGS data analysis pipeline, clinical samples were pooled into two NGS groups to reduce sequencing costs, and the depth and coverage of assembled contigs were effectively increased using an iterative mapping approach. PCR was individually performed for each specimen according to the NGS-predicted viral type. We successfully detected previously unidentified respiratory viruses in 26 of 40 specimens using our proposed NGS pipeline. Two dominant populations within the detected viruses were human rhinoviruses (HRVs; n = 14) and human coronavirus NL63 (n = 8), followed by human parainfluenza virus (HPIV), human parechovirus, influenza A virus, respiratory syncytial virus (RSV), and human metapneumovirus. This is the first study reporting the complete genome sequences of HRV-A101, HRV-C3, HPIV-4a, and RSV, as well as an analysis of their genetic variants, in Taiwan. These results demonstrate that this NGS pipeline allows to detect viruses which were not identified by routine diagnostic assays, directly from clinical samples.


Subject(s)
Metagenomics/methods , RNA, Viral/genetics , Respiratory Tract Infections/virology , Child , Genetic Variation , Genome, Viral , Humans , RNA, Viral/classification , RNA, Viral/isolation & purification
10.
Future Oncol ; 13(13): 1173-1180, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28498036

ABSTRACT

This study aimed to detect the effect of combination radiotherapy and cantharidin on lung cancer growth. We found that combination therapy with radiotherapy and cantharidin was more effective in inhibiting the tumor growth than radiotherapy or cantharidin alone. It decreased the percentage of CD4+ Tregs and enhanced the percentage of CD8+ T cells, CD4+ Teff cells when comparing to that of single treatment. Combination therapy promoted a great increase in double producing CD8+ T cells and CD4+ Teff cells in tumor infiltrating lymphocytes. Overexpression of CTLA4 reversed the inhibitory action of combination treatment on cancer growth. Our data suggest that combining radiotherapy and cantharidin may have synergistic effects in driving tumor rejection by increasing T-cell infiltration, proliferation and cytokine production.


Subject(s)
Carcinoma, Lewis Lung/drug therapy , Carcinoma, Lewis Lung/radiotherapy , Lung Neoplasms/drug therapy , Lung Neoplasms/radiotherapy , Animals , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/radiation effects , CD8-Positive T-Lymphocytes/drug effects , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/radiation effects , CTLA-4 Antigen/immunology , Cantharidin/administration & dosage , Cantharidin/adverse effects , Carcinoma, Lewis Lung/immunology , Carcinoma, Lewis Lung/pathology , Cell Proliferation/drug effects , Cell Proliferation/radiation effects , Combined Modality Therapy , Disease Models, Animal , Humans , Lung Neoplasms/immunology , Lung Neoplasms/pathology , Lymphocytes, Tumor-Infiltrating/drug effects , Lymphocytes, Tumor-Infiltrating/immunology , Lymphocytes, Tumor-Infiltrating/radiation effects , Mice , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/radiation effects
12.
Zhonghua Fu Chan Ke Za Zhi ; 48(5): 344-7, 2013 May.
Article in Zh | MEDLINE | ID: mdl-24016476

ABSTRACT

OBJECTIVE: To investigate diagnostic approaches of cervical glandular intraepithelial neoplasia (CGIN) for improving the diagnostic levels of CGIN. METHODS: Clinical data of 106 cases with CGIN admitted in hospital from Jan.2008 to Dec. 2010 were analyzed retrospectively.All data from preoperative thin-prep cytologic test (TCT), cervical biopsies and postoperative pathological examination of the excised cervical tissues were reviewed. RESULTS: Among 106 patients, 62 cases (58.5%, 62/106) were low grade CGIN (L-CGIN), 44 cases (41.5%, 44/106) were high grade CGIN (H-CGIN); 25 cases (23.6%, 25/106) were pure CGIN and 81 cases (76.4%, 81/106) were CGIN mixed with cervical intraepithelial neoplasia (CIN). Fifteen cases (14.2%, 15/106) were found atypical glandular cell (AGC) by TCT. In the 15 cases, there were 4 cases (6.5%, 4/62) L-CGIN, and 11 cases (25.0%, 11/44) H-CGIN, there was significant difference between the two groups (P < 0.05); among 15 cases with AGC, 11 cases of them (44.0%, 11/25) were pure CGIN, 4 cases (4.9%, 4/81) mixed with CIN, in which there were significant difference (P < 0.01).Seven cases (25.0%, 7/28) were detected glandular lesions in 28 cases by endocervical curettage (ECC). Totally 23 cases (22.8%, 23/101) were detected CGIN by colposcopy-directed biopsy, 11 cases (19.0%, 11/58) were with L-CGIN, 12 cases (27.9%, 12/43) H-CGIN, there was no significant difference between them (P > 0.05).Among the 23 cases, 13 cases (52.0%, 13/25) were pure CGIN, 10 cases (12.3%, 10/81) CGIN mixed with CIN, which showed significant difference (P < 0.01). All 106 patients were treated, 101 cases treated with cervical conization and 5 cases performed hysterectomy; 23 cases were diagnosed CGIN preoperation, the ratio of preoperative diagnosis was 21.7% (23/106), 83 cases (80.3%, 83/106) diagnosed postoperatively. CONCLUSIONS: Routine diagnostic methods of CGIN were not satisfaction, most CGIN were diagnosed after cervical resection.Cervical conization may play a very important role in diagnosis of CGIN.The positivity of TCT in H-CGIN was higher than L-CGIN. There was no different in diagnosing different CGIN grades by colposcopy-directed biopsy. The ratio of preoperative diagnosis of pure CGIN was higher than those with CGIN mixed with CIN.


Subject(s)
Cervix Uteri/pathology , Cytological Techniques/methods , Uterine Cervical Dysplasia/diagnosis , Uterine Cervical Neoplasms/diagnosis , Adenocarcinoma/diagnosis , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adult , Aged , Biopsy/methods , Cervix Uteri/surgery , Colposcopy , Conization , Diagnosis, Differential , Female , Humans , Middle Aged , Precancerous Conditions/diagnosis , Precancerous Conditions/pathology , Retrospective Studies , Sensitivity and Specificity , Uterine Cervical Neoplasms/pathology , Uterine Cervical Neoplasms/surgery , Uterine Cervical Dysplasia/pathology , Uterine Cervical Dysplasia/surgery
13.
Zhonghua Fu Chan Ke Za Zhi ; 48(3): 171-6, 2013 Mar.
Article in Zh | MEDLINE | ID: mdl-23849937

ABSTRACT

OBJECTIVE: To investigate the expression of vitronectin (VN) in placental basal plate and its relationship with the pathogenesis of severe preeclampsia. METHODS: From March 2010 to December 2011, 17 patients with early-onset severe preeclampsia who delivered in the Second Hospital of Jilin University were recruited as the early-onset severe preeclampsia group; and 16 women were recruited as the late-onset severe preeclampsia group. Meanwhile, 15 healthy pregnant women who delivered before 34 weeks were defined as the early control group (termination of pregnancy was carried out because of fetal heart malformations), and 15 healthy pregnant women delivered after 34 weeks were defined as the late control group. Immunohistochemistry and semi-quantitative reverse transcription (RT)-PCR were used to investigate the expression of VN protein and mRNA in the placental infarct center and its surrounding tissue of placental basal plate. The levels of serum prothrombin time (PT), part thromboplastin time (APTT) and fibrinogen (FIb) were detected and the international normalized ratio (INR) was calculated. The correlation of abnormal coagulation markers and VN expression levels in the early-onset severe preeclampsia group and the early control group was studied. RESULTS: (1) VN protein was detected in all placental basal plate of the four groups. It was highly expressed in the necrotic tissue of placental infarct center and weakly expressed in the tissue far from the infarcted area. (2) The mean levels of VN protein expression in placental basal plate of the early-onset severe preeclampsia group, the late-onset severe preeclampsia group, the late control group and the early control group were 0.152 ± 0.019, 0.113 ± 0.023, 0.095 ± 0.014 and 0.055 ± 0.010, respectively. And the differences between the groups were statistically significant (P < 0.01). The VN protein expression in placental infarct center, infarct edge, peri-infarct tissue and tissue far from the infarcted area gradually reduced, and the differences were statistically significant (P < 0.01). Compared with the same areas of each group, the differences were not statistically significant (P > 0.05). (3) VN mRNA were detectable in infarct center, infarct edge, per-infarct tissue and tissue far from the infarcted area of placental basal plate. In the early-onset severe preeclampsia group and the early control group, it was statistically higher in infarct center than in tissue far from the infarcted area (P < 0.05). (4) PT of the early-onset severe preeclampsia group was (9.45 ± 0.63) s, significantly shorter than that of the early control group [(9.88 ± 0.17) s, P < 0.05]. While there was no statistically significant difference in APTT, FIB and INR among the four groups (P > 0.05). (5) In the early-onset severe preeclampsia group, VN expression level and PT were significantly negative correlated (r = -0.612, P < 0.05); while in the early control group there was no correlation (r = 0.489, P > 0.05). CONCLUSION: VN was highly expressed in placental basal plate of the early-onset severe preeclampsia group, which caused the imbalance of coagulation and fibrinolysis system and the pathogenesis of severe preeclampsia.


Subject(s)
Placenta/metabolism , Pre-Eclampsia/metabolism , Vitronectin/metabolism , Adult , Case-Control Studies , Female , Fibrinogen/metabolism , Humans , Immunohistochemistry , Placenta/pathology , Placenta/physiopathology , Pre-Eclampsia/physiopathology , Pregnancy , Pregnancy Trimester, Third , Prothrombin Time , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reverse Transcriptase Polymerase Chain Reaction , Severity of Illness Index , Vitronectin/genetics , Young Adult
14.
Curr Probl Cancer ; 47(6): 101014, 2023 Dec.
Article in English | MEDLINE | ID: mdl-37718231

ABSTRACT

Advanced-stage ovarian cancer is usually associated with peritoneal carcinomatosis. This study evaluates the prognostic role of the Peritoneal Cancer Index (PCI) in predicting the survival of patients with ovarian cancer. A literature search was conducted in electronic databases (Google Scholar, PubMed, Ovid, and Science Direct) and study selection was based on precise eligibility criteria. Random-effects meta-analyses were performed to estimate survival with low and high PCI scores and to pool hazard ratios (HR) of survival between lower and higher PCI scores. A total of 20 studies (2588 patients) were included. Median follow-up was 39 months [95%CI: 25, 54]. Complete cytoreduction rate was 80% [95% CI: 73, 87]. The median PCI score was 11.3 [95% CI: 9.9, 12.7]. Median survival was 56.7 months [95% CI: 45.2, 68.2] with below and 28.8 months [95% CI: 23.0, 34.6] with above any PCI cutoff. Most studies used PCI cutoffs between 10 and 20. The median progression-free survival was 23.7 months [95% CI: 16.5, 30.8] with below and 11.9 months [95% CI: 5.9, 17.9] with above any PCI cutoff. 5-year survival rates were 61.3% [95% CI: 49.9, 72.8] with PCI<10 cutoffs, 21.7% [95% CI: 11.6, 31.8] with PCI>10 cutoffs, 50.1% [95% CI: 39.0, 61.2] with PCI<20 cutoffs, and 21.7% [95% CI: 16.2, 27.1] with PCI>20 cutoffs. Pooled analysis of HRs showed that a higher PCI score was associated with worse survival in both univariate (HR 2.14 [95%CI: 1.63, 2.66]) and multivariate (HR 1.10 [95% CI: 1.02, 1.18]) analyses. In a set of studies that used varying PCI cutoffs, the PCI has been found to have a significant inverse association with the survival of patients with advanced ovarian cancer who underwent cytoreductive surgery.


Subject(s)
Cytoreduction Surgical Procedures , Ovarian Neoplasms , Humans , Female , Prognosis , Retrospective Studies , Ovarian Neoplasms/surgery , Carcinoma, Ovarian Epithelial , Survival Rate
15.
Front Cell Infect Microbiol ; 13: 1269329, 2023.
Article in English | MEDLINE | ID: mdl-37900310

ABSTRACT

Background: Influenza A virus (IAV) infection poses a persistent global health challenge, necessitating a nuanced grasp of host immune responses for optimal interventions. While the interplay between aging, immunosenescence, and IAV is recognized as key in severe lower respiratory tract infections, the role of specific patient attributes in shaping innate immune reactions and inflammasome activity during IAV infection remains under-investigated. In this study, we utilized an ex vivo infection model of human lung tissues with H3N2 IAV to discern relationships among patient demographics, IAV nucleoprotein (NP) expression, toll-like receptor (TLR) profiles, PD-1/PD-L1 markers, and cytokine production. Methods: Our cohort consisted of thirty adult patients who underwent video-assisted thoracoscopic surgery during 2018-2019. Post-surgical lung tissues were exposed to H3N2 IAV for ex vivo infections, and the ensuing immune responses were profiled using flow cytometry. Results: We observed pronounced IAV activity within lung cells, as indicated by marked NP upregulation in both epithelial cells (P = 0.022) and macrophages (P = 0.003) in the IAV-exposed group relative to controls. Notably, interleukin-2 levels correlated with variations in TLR1 expression on epithelial cells and PD-L1 markers on macrophages. Age emerged as a modulating factor, dampening innate immune reactions, as evidenced by reduced interleukin-2 and interferon-γ concentrations (both adjusted P < 0.05). Intriguingly, a subset of participants with pronounced tumor necrosis factor-alpha post-mock infection (Cluster 1) showed attenuated cytokine responses in contrast to their counterparts in Cluster 2 and Cluster 3 (all adjusted P < 0.05). Individuals in Cluster 2, characterized by a low post-mock infection NP expression in macrophages, exhibited reduced variations in both NP and TLR1-3 expressions on these cells and a decreased variation in interleukin-2 secretion in comparison to their Cluster 3 counterparts, who were identified by their elevated NP macrophage expression (all adjusted P < 0.05). Conclusion: Our work elucidates the multifaceted interplay of patient factors, innate immunity, and inflammasome responses in lung tissues subjected to ex vivo H3N2 IAV exposure, reflecting real-world lower respiratory tract infections. While these findings provide a foundation for tailored therapeutic strategies, supplementary studies are requisite for thorough validation and refinement.


Subject(s)
Influenza A virus , Influenza, Human , Adult , Humans , Inflammasomes , Interleukin-2 , B7-H1 Antigen , Influenza A Virus, H3N2 Subtype , Toll-Like Receptor 1 , Immunity, Innate/physiology , Lung/pathology , Cytokines
16.
Microbes Infect ; 25(1-2): 105044, 2023.
Article in English | MEDLINE | ID: mdl-36096357

ABSTRACT

The World Health Organization has highlighted the importance of an international standard (IS) for severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) neutralizing antibody titer detection to calibrate diagnostic techniques. We applied an IS to calibrate neutralizing antibody titers (NTs) (international units/mL) in response to coronavirus disease 2019 (COVID-19) vaccination. Moreover, the association between different factors and neutralizing antibodies was analyzed. A total of 1667 serum samples were collected from participants receiving different COVID-19 vaccines. Antibody titers were determined by a microneutralization assay using live viruses in a biosafety level 3 (BSL-3) laboratory and a commercial serological MeDiPro kit. The titer determined using the MeDiPro kit was highly correlated with the NT determined using live viruses and calibrated using IS. Fever and antipyretic analgesic treatment were related to neutralizing antibody responses in ChAdOx1-S and BNT162b2 vaccinations. Individuals with diabetes showed a low NT elicited by MVC-COV1901. Individuals with hypertension receiving the BNT162b2 vaccine had lower NTs than those without hypertension. Our study provided the international unit (IU) values of NTs in vaccinated individuals for the development of vaccines and implementation of non-inferiority trials. Correlation of the influencing factors with NTs can provide an indicator for selecting COVID-19 vaccines based on personal attributes.


Subject(s)
COVID-19 , Hypertension , Humans , COVID-19 Vaccines , BNT162 Vaccine , COVID-19/prevention & control , SARS-CoV-2 , Antibodies, Neutralizing , Vaccination , Antibodies, Viral
19.
World J Clin Cases ; 10(35): 12996-13005, 2022 Dec 16.
Article in English | MEDLINE | ID: mdl-36569010

ABSTRACT

BACKGROUND: The purpose of this study was to report the rare case of a pregnant woman with congenital dysfibrinogenemia (CD) misdiagnosed as acute fatty liver. She was treated according to the principles of acute fatty liver but achieved good clinical results. CASE SUMMARY: A 30-year-old woman presented with 39 (6/7) wk of menopause and 6 h of irregular abdominal pain and attended our hospital. Emergency surgery was performed due to fetal distress. Postoperative management followed the treatment principle of acute fatty liver. DNA sequencing was carried out on the pregnant woman and her pedigree. Coagulation values of the patient on admission were prothrombin time 33.7 s, activated partial thromboplastin time 60.4 s, thrombin time 45.2 s, and fibrinogen 0.60 g/L. DNA sequencing results showed that the woman carried a pathogenic heterozygous variation of the fibrinogen alpha chain gene (FGA), which is closely related to hereditary fibrinogen abnormality, and the mutation site was located in p.R350H. After a follow-up period of 12 mo, the mother and her newborn had a good prognosis without bleeding or thrombosis. CONCLUSION: Pregnant women with CD may have atypical symptoms, which can easily lead to misdiagnosis. In addition, treatment can be attempted according to the principles of acute fatty liver management. This rare pregnant patient with CD was caused by a novel FGA (p.R350H) gene mutation.

20.
Cells ; 11(5)2022 02 23.
Article in English | MEDLINE | ID: mdl-35269402

ABSTRACT

Avian influenza A (H7N9) virus infections frequently lead to acute respiratory distress syndrome and death in humans. The emergence of H7N9 virus infections is a serious public health threat. To identify virus-host interaction differences between the highly virulent H7N9 and pandemic influenza H1N1 (pdmH1N1), RNA sequencing was performed of normal human bronchial epithelial (NHBE) cells infected with either virus. The transcriptomic analysis of host cellular responses to viral infection enables the identification of potential cellular factors related to infection. Significantly different gene expression patterns were found between pdmH1N1- and H7N9-infected NHBE cells. In addition, the H7N9 virus infection induced strong immune responses, while cellular repair mechanisms were inhibited. The differential expression of specific factors observed between avian H7N9 and pdmH1N1 influenza virus strains can account for variations in disease pathogenicity. These findings provide a framework for future studies examining the molecular mechanisms underlying the pathogenicity of avian H7N9 virus.


Subject(s)
Influenza A Virus, H1N1 Subtype , Influenza A Virus, H5N1 Subtype , Influenza A Virus, H7N9 Subtype , Influenza, Human , Animals , Epithelial Cells , Humans , Influenza A Virus, H5N1 Subtype/genetics , Influenza A Virus, H7N9 Subtype/genetics , Transcriptome/genetics
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