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Given that esophageal cancer is highly malignant, the discovery of novel prognostic markers is eagerly awaited. We performed serological identification of antigens by recombinant cDNA expression cloning (SEREX) and identified SKI proto‐oncogene protein and transmembrane p24 trafficking protein 5 (TMED5) as antigens recognized by serum IgG antibodies in patients with esophageal carcinoma. SKI and TMED5 proteins were expressed in Escherichia coli, purified by affinity chromatography, and used as antigens. The serum anti‐SKI antibody (s‐SKI‐Ab) and anti‐TMED5 antibody (s‐TMED5‐Ab) levels were significantly higher in 192 patients with esophageal carcinoma than in 96 healthy donors. The presence of s‐SKI‐Abs and s‐TMED5‐Abs in the patients' sera was confirmed by western blotting. Immunohistochemical staining showed that the TMED5 protein was highly expressed in the cytoplasm and nuclear compartments of the esophageal squamous cell carcinoma tissues, whereas the SKI protein was localized predominantly in the nuclei. Regarding the overall survival in 91 patients who underwent radical surgery, the s‐SKI‐Ab‐positive and s‐TMED5‐Ab‐negative statuses were significantly associated with a favorable prognosis. Additionally, the combination of s‐SKI‐Ab‐positive and s‐TMED5‐Ab‐negative cases showed an even clearer difference in overall survival as compared with that of s‐SKI‐Ab‐negative and s‐TMED5‐Ab‐positive cases. The s‐SKI‐Ab and s‐TMED5‐Ab biomarkers are useful for diagnosing esophageal carcinoma and distinguishing between favorable and poor prognoses. The s‐SKI‐Ab and s‐TMED5‐Ab levels were significantly higher in patients with esophageal carcinoma than in HDs. These antibody markers are useful for predicting the prognosis of patients with esophageal carcinoma individually or in combination.

Taiwan experienced two waves of imported infections with Coronavirus Disease 2019 (COVID-19). This study aimed at investigating the genomic variation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in Taiwan and compared their evolutionary trajectories with the global strains. We performed culture and full-genome sequencing of SARS-CoV-2 strains followed by phylogenetic analysis. A 382-nucleotides deletion in open reading frame 8 (ORF8) was found in a Taiwanese strain isolated from a patient on February 4, 2020 who had a travel history to Wuhan. Patients in the first wave also included several sporadic, local transmission cases. Genomes of 5 strains sequenced from clustered infections were classified into a new clade with ORF1ab-V378I mutation, in addition to 3 dominant clades ORF8-L84S, ORF3a-G251V and S-D614G. This highlighted clade also included some strains isolated from patients who had a travel history to Turkey and Iran. The second wave mostly resulted from patients who had a travel history to Europe and Americas. All Taiwanese viruses were classified into various clades. Genomic surveillance of SARS-CoV-2 in Taiwan revealed a new ORF8-deletion mutant and a virus clade that may be associated with infections in the Middle East, which contributed to a better understanding of the global SARS-CoV-2 transmission dynamics.

ObjectiveTo explore how lncRNA SNHG14 modulates the biological features of hepatocellular carcinoma (HCC) cells by regulating SOX9 via mediating miR-206.MethodsHCC 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.ResultsSNHG14 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.ConclusionInhibition 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.

The relationship between energy production and cancer is attracting attention. This study aimed to investigate the clinicopathological significance of fumarate hydratase (FH), a tricarboxylic acid cycle enzyme, in gastric cancer using autoantibodies as biomarkers. The study analyzed 116 patients who underwent gastric cancer surgery and 96 healthy controls. Preoperative serum FH autoantibody (s-FH-Ab) titers were analyzed using an immunosorbent assay with an amplified luminescent proximity homogeneous assay. Receiver operating characteristic analysis was used to determine the cutoff s-FH-Ab titer. Clinicopathological factors and prognosis were compared between the high and low s-FH-Ab groups. The s-FH-Ab levels were significantly higher in the gastric cancer group than in the control group (p = 0.01). Levels were elevated even in patients with stage I gastric cancer compared with healthy controls (p = 0.02). A low s-FH-Ab level was significantly associated with distant metastasis (p = 0.01), peritoneal dissemination (p < 0.05), and poor overall survival (p < 0.01). Multivariate analysis revealed that low s-FH-Ab levels were an independent risk factor for poor prognosis (p < 0.01). Therefore, s-FH-Ab levels may be a useful biomarker for early diagnosis and the prediction of prognosis in patients with gastric cancer.

The presence of disease-specific antigens and autoantibodies in the sera of patients with atherosclerosis-related diseases has been widely reported and is considered to result from inflammation of the arterial wall and the involvement of immune factors. The aim of this study was to identify a novel antibody in patients with ischemic stroke by serological identification of antigens using recombinant cDNA expression cloning from patients who had a transient ischemic attack (TIA). We identified the serpin peptidase inhibitor, clade E member 1 (SERPINE1), as a candidate antigen. The serum anti-SERPINE1 antibody levels quantified using amplified luminescent proximity homogeneous assay-linked immunosorbent assay were significantly higher in patients with ischemic stroke, including those with acute cerebral infarction (aCI), TIA, and chronic cerebral infarction, than in healthy donors. The antibody levels were strongly associated with old age, female sex, and presence of hypertension, diabetes mellitus, and cardiovascular disease. Age and intima-media thickness of the carotid artery were positively correlated with antibody levels, which suggests that SERPINE1 may reflect the progression of atherosclerosis. In a multivariate analysis, SERPINE1 antibody level was an independent predictor of aCI. Thus, the serum levels of anti-SERPINE1 antibody could potentially serve as a biomarker of atherothrombotic infarction.

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.

Inflammation is closely associated with cerebrovascular diseases, cardiovascular diseases, diabetes, and cancers, and it is accompanied by the development of autoantibodies in the early stage of inflammation-related diseases. Hence, it is meaningful to discover novel antibody biomarkers targeting inflammation-related diseases. In this study, Jumonji C-domain-containing 6 (JMJD6) was identified by the serological identification of antigens through recombinant cDNA expression cloning. In particular, JMJD6 is an antigen recognized in serum IgG from patients with unstable angina pectoris (a cardiovascular disease). Then, the serum antibody levels were examined using an amplified luminescent proximity homogeneous assay-linked immunosorbent assay and a purified recombinant JMJD6 protein as an antigen. We observed elevated levels of serum anti-JMJD6 antibodies (s-JMJD6-Abs) in patients with inflammation-related diseases such as ischemic stroke, acute myocardial infarction (AMI), diabetes mellitus (DM), and cancers (including esophageal cancer, EC; gastric cancer; lung cancer; and mammary cancer), compared with the levels in healthy donors. The s-JMJD6-Ab levels were closely associated with some inflammation indicators, such as C-reactive protein and intima–media thickness (an atherosclerosis index). A better postoperative survival status of patients with EC was observed in the JMJD6-Ab-positive group than in the negative group. An immunohistochemical analysis showed that JMJD6 was highly expressed in the inflamed mucosa of esophageal tissues, esophageal carcinoma tissues, and atherosclerotic plaques. Hence, JMJD6 autoantibodies may reflect inflammation, thereby serving as a potential biomarker for diagnosing specific inflammation-related diseases, including stroke, AMI, DM, and cancers, and for prediction of the prognosis in patients with EC.

This systematic review was designed to evaluate the efficacy of neoadjuvant chemotherapy with radical surgery vs radical surgery alone for cervical cancer. A computerized search was done for trials from PubMed, EMBASE, CENTRAL, and Cochrane Database of Systematic Reviews. The trials included neoadjuvant chemotherapy plus radical surgery vs radical surgery alone. We measured overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), local and distant recurrence, lymph node metastasis, and parametrial infiltration per patient. In all, 13 studies involving 2,158 subjects were included. In regard to OS, DFS, PFS, local and distant recurrence, and parametrial infiltration, neoadjuvant chemotherapy plus radical surgery was similar to radical surgery alone. Among them, subgroup analysis of eight studies involving 1,544 patients with locally advanced cervical cancer (FIGO stage IB2-IIB) showed that neoadjuvant chemotherapy (NACT) plus radical surgery significantly improved OS, and decreased local and distant recurrence rates, lymph node metastasis rate, and the level of parametrial infiltration compared to radical surgery alone. The present study demonstrates that preoperative NACT is now an accepted effective procedure in selected patients with locally advanced cervical cancer (FIGO stage IB2-IIB). However, the relationship between NACT and longer DFS and PFS cannot be demonstrated by this meta-analysis. Thus, the decision to use or not to use NACT before radical surgery depends on the surgeon's experience and clinical judgment. Nevertheless, further research in this field is urgently needed to confirm it.

Objective In this meta-analysis, we aimed to evaluate the oncological outcomes of preoperative neoadjuvant chemotherapy followed by radical surgery compared with radical surgery alone for treatment of International Federation of Gynecology and Obstetrics (FIGO) stage I–II cervical cancer. Method We searched for studies comparing the safety and efficacy of neoadjuvant chemotherapy plus surgery versus surgery alone in treatment outcomes of locally advanced cervical cancer. Meta-analysis was used to calculate the pooled odds ratios with corresponding 95% confidence intervals (CI). Results Sixteen studies were included in our analysis. Pooled analysis of overall survival rate [odds ratio (OR) = 1.09, 95% CI: 0.83–1.43] and progression-free survival rate (OR = 1.10, 95% CI: 0.77–1.57) showed that preoperative neoadjuvant chemotherapy did not have a benefit compared with surgery alone in terms of survival rates. The pooled results for postoperative parameters indicated that preoperative neoadjuvant chemotherapy followed by radical surgery was associated with a high rate of vascular space involvement (OR = 0.25, 95% CI: 0.17–0.35) and parametrial infiltration (OR = 0.60, 95% CI: 0.45–0.79). Conclusions This meta-analysis indicated that surgery following neoadjuvant chemotherapy for FIGO stage I–II cervical cancer and surgery alone had similar oncological outcomes.

An avian influenza A H7N9 virus emerged in March 2013 and caused a remarkable number of human fatalities. Genome variability in these viruses may provide insights into host adaptability. We scanned over 140 genomes of the H7N9 viruses isolated from humans and identified 104 positions that exhibited seven or more amino acid substitutions. Approximately half of these substitutions were identified in the influenza ribonucleoprotein (RNP) complex. Although PB2 627K of the avian virus promotes replication in humans, 45 of the 147 investigated PB2 sequences retained the E signature at this position, which is an avian characteristic. We discovered 10 PB2 substitutions that covaried with K627E. An RNP activity assay showed that Q591K, D701N, and M535L restored the polymerase activity in human cells when 627K transformed to an avian-like E. Genomic analysis of the human-isolated avian influenza virus is crucial in assessing genome variability, because relationships between position-specific variations can be observed and explored. In this study, we observed alternative positions that can potentially compensate for PB2 627K, a well-known marker for cross-species infection. An RNP assay suggested Q591K, D701N, and M535L as potential markers for an H7N9 virus capable of infecting humans.