RESUMO
OBJECTIVE: To investigate the effects of repeated vaccination with ancestral SARS-CoV-2 (Wuhan-hu-1)-based inactivated, recombinant protein subunit or vector-based vaccines on the neutralizing antibody response to Omicron subvariants. METHODS: Individuals who received four-dose vaccinations with the Wuhan-hu-1 strain, individuals who were infected with the BA.5 variant alone without prior vaccination, and individuals who experienced a BA.5 breakthrough infection following receiving 2-4 doses of the Wuhan-hu-1 vaccine were enrolled. Neutralizing antibodies against D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 were detected using a pseudovirus-based neutralization assay. Antigenic cartography was used to analyze cross-reactivity patterns among D614G, BA.5, XBB.1.5, EG.5.1, and BA.2.86 and sera from individuals. RESULTS: The highest neutralizing antibody titers against D614G were observed in individuals who only received four-dose vaccination and those who experienced BA.5 breakthrough infection, which was also significantly higher than the antibody titers against XBB.1.5, EG.5.1, and BA.2.86. In contrast, only BA.5 infection elicited comparable neutralizing antibody titers against the tested variants. While neutralizing antibody titers against D614G or BA.5 were similar across the cohorts, the neutralizing capacity of antibodies against XBB.1.5, EG.5.1, and BA.2.86 was significantly reduced. BA.5 breakthrough infection following heterologous booster induced significantly higher neutralizing antibody titers against the variants, particularly against XBB.1.5 and EG.5.1, than uninfected vaccinated individuals, only BA.5 infected individuals, or those with BA.5 breakthrough infection after primary vaccination. CONCLUSIONS: Our findings suggest that repeated vaccination with the Wuhan-hu-1 strain imprinted a neutralizing antibody response toward the Wuhan-hu-1 strain with limited effects on the antibody response to the Omicron subvariants.
RESUMO
[This retracts the article on p. 1531 in vol. 15, PMID: 37746647.].
RESUMO
BACKGROUND: Peripherally Inserted Central Catheter (PICC) is essential in neonatal care, especially for critically ill infants. Traditional training for neonatal PICC insertion faces challenges such as high costs and limited practice opportunities. Virtual simulation technology has emerged as a potential training tool, providing a realistic, risk-free learning environment. OBJECTIVES: The study aimed to assess the effectiveness of a virtual simulation teaching system in neonatal PICC care training, focusing on improving nursing students' knowledgeï¼ skills and interest in pediatric nursing. DESIGN: A quasi-experimental design was used, with assessments conducted before and after the activity. PARTICIPANTS: The study involved 58 graduate nursing students from China Medical University, divided into experimental and control groups. METHODS: The System Usability Scale (SUS) was utilized to assess teachers' experiences with the PICC virtual simulation software. Students' perceptions of the software and their interest in pediatric nursing were measured using Self-Administered Questionnaires. Furthermore, Theoretical and Operational Assessments were applied to determine the extent of students' knowledge and practical skills before and after experimentation. RESULTS: Teachers and students have favorably evaluated the software system, with notable improvements in theoretical scores following testing. While the virtual simulation system does not enhance practical skills, it does increase student interest in pediatric nursing and employment. CONCLUSIONS: This neonatal virtual simulation software serves as a complement to, rather than a replacement for, traditional clinical training. Its integration into educational programs significantly enhances learning outcomes.
Assuntos
Cateterismo Periférico , Competência Clínica , Enfermagem Neonatal , Estudantes de Enfermagem , Humanos , Enfermagem Neonatal/educação , Enfermagem Neonatal/métodos , Enfermagem Neonatal/normas , Estudantes de Enfermagem/estatística & dados numéricos , Estudantes de Enfermagem/psicologia , Cateterismo Periférico/métodos , Cateterismo Periférico/enfermagem , Feminino , Competência Clínica/normas , Competência Clínica/estatística & dados numéricos , Masculino , China , Recém-Nascido , Inquéritos e Questionários , Treinamento por Simulação/métodos , Adulto , Educação de Pós-Graduação em Enfermagem/métodos , Avaliação Educacional/métodosRESUMO
Background: Epidermal growth factor-like repeats and discoidin I-like domains 3 (EDIL3) is a secreted extracellular matrix protein implicated in diverse physiological and pathological processes including embryonic development, angiogenesis, and anti-inflammatory responses. Recent reports have indicated that EDIL3 play critical roles in carcinogenesis and progression of many cancers. Herein, we performed a pan-cancer investigation to study the potential functions of EDIL3 in various cancers and experimentally validate its function in gastric cancer (GC). Methods: We analysed EDIL3 expression profiles in different tumours using The Cancer Genome Atlas database. The Kaplan-Meier Plotter was used to investigate the prognostic value of EDIL3, while receiver operating characteristic curve was performed to analyze its diagnostic efficacy. Several bioinformatics tools were used to study the association between EDIL3 and promoter methylation, gene enrichment analysis, immune infiltration, immune-related genes, and drug sensitivity. Molecular biology experiments were conducted to validate the tumorigenic effects of EDIL3. Results: EDIL3 is variably expressed in different cancers and is closely associated with clinical outcomes. An inverse correlation between EDIL3 and DNA methylation has been observed in 13 cancers. Enrichment analysis indicated that EDIL3 is correlated with many cellular pathways such as extracellular matrix receptor interactions and focal adhesion. EDIL3 was tightly associated with immune infiltration and immune checkpoints. EDIL3 knockdown can promote GC calls apoptosis while preventing proliferation, migration, and invasion in vitro. Conclusion: EDIL3 is a promising prognostic, diagnostic, and immunological biomarker in various cancers, which could be applied as a new target for cancer therapy.
RESUMO
The ongoing emergence of SARS-CoV-2 variants poses challenges to the immunity induced by infections and vaccination. We conduct a 6-month longitudinal evaluation of antibody binding and neutralization of sera from individuals with six different combinations of vaccination and infection against BA.5, XBB.1.5, EG.5.1, and BA.2.86. We find that most individuals produce spike-binding IgG or neutralizing antibodies against BA.5, XBB.1.5, EG.5.1, and BA.2.86 2 months after infection or vaccination. However, compared to ancestral strain and BA.5 variant, XBB.1.5, EG.5.1, and BA.2.86 exhibit comparable but significant immune evasion. The spike-binding IgG and neutralizing antibody titers decrease in individuals without additional antigen exposure, and <50% of individuals neutralize XBB.1.5, EG.5.1, and BA.2.86 during the 6-month follow-up. Approximately 57% of the 107 followed up individuals experienced an additional infection, leading to improved binding IgG and neutralizing antibody levels against these variants. These findings provide insights into the impact of SARS-CoV-2 variants on immunity following repeated exposure.
Assuntos
Anticorpos Neutralizantes , Anticorpos Antivirais , Vacinas contra COVID-19 , COVID-19 , Imunoglobulina G , SARS-CoV-2 , Glicoproteína da Espícula de Coronavírus , Vacinação , Humanos , SARS-CoV-2/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , COVID-19/virologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/sangue , Anticorpos Neutralizantes/imunologia , Anticorpos Neutralizantes/sangue , Vacinas contra COVID-19/imunologia , Imunoglobulina G/imunologia , Imunoglobulina G/sangue , Glicoproteína da Espícula de Coronavírus/imunologia , Feminino , Masculino , Adulto , Pessoa de Meia-Idade , Formação de Anticorpos/imunologiaRESUMO
INTRODUCTION: Dry eye (DE) is a multifactorial ocular surface disease causing considerable medical, social and financial implications. Currently, there is no recognised long-term, effective treatment to alleviate DE. Clinical evidence shows that electroacupuncture (EA) can improve DE symptoms, tear secretion and tear film stability, but it remains controversial whether it is just a placebo effect. We aim to provide solid clinical evidence for the EA treatment of DE. METHODS AND ANALYSIS: This is a multicentre, randomised, sham-controlled trial. A total of 168 patients with DE will be enrolled and randomly assigned to EA or sham EA groups to receive 4-week consecutive treatments and follow-up for 24 weeks. The primary outcome is the change in the non-invasive tear break-up time (NIBUT) from baseline to week 4. The secondary outcomes include tear meniscus height, the Schirmer I test, corneal and conjunctival sensation, the ocular surface disease index, corneal fluorescein staining, the numerical rating scale and the Chinese DE-related quality of life scale. ETHICS AND DISSEMINATION: The trial protocol and informed consent were approved by the Ethics Committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine (identifier: 2021-119), Shanghai Eye Disease Prevention and Treatment Center (identifier: 2022SQ003) and Eye and ENT Hospital of Fudan University (identifier: 2022014). TRIAL REGISTRATION NUMBER: NCT05552820.
Assuntos
Síndromes do Olho Seco , Eletroacupuntura , Humanos , Qualidade de Vida , Método Simples-Cego , China , Resultado do Tratamento , Síndromes do Olho Seco/terapia , Síndromes do Olho Seco/diagnóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como AssuntoRESUMO
BACKGROUND: Extensive evidence has illustrated the promotive role of integrin binding sialoprotein (IBSP) in the progression of multiple cancers. However, little is known about the functions of IBSP in gastric cancer (GC) progression. AIM: To investigate the mechanism underlying the regulatory effects of IBSP in GC progression, and the relationship between IBSP and cleavage and polyadenylation factor 6 (CPSF6) in this process. METHODS: The mRNA and protein expression of relevant genes were assessed through real-time quantitative polymerase chain reaction and Western blot, respectively. Cell viability was evaluated by Cell Counting Kit-8 assay. Cell invasion and migration were evaluated by Transwell assay. Pyroptosis was measured by flow cytometry. The binding between CPSF6 and IBSP was confirmed by luciferase reporter and RNA immunoprecipitation (RIP) assays. RESULTS: IBSP exhibited higher expression in GC tissues and cell lines than in normal tissues and cell lines. IBSP knockdown suppressed cell proliferation, migration, and invasion but facilitated pyroptosis. In the exploration of the regulatory mechanism of IBSP, potential RNA binding proteins for IBSP were screened with catRAPID omics v2.0. The RNA-binding protein CPSF6 was selected due to its higher expression in stomach adenocarcinoma. Luciferase reporter and RIP assays revealed that CPSF6 binds to the 3'-untranslated region of IBSP and regulates its expression. Knockdown of CPSF6 inhibited cell proliferation, migration, and invasion but boosted pyroptosis. Through rescue assays, it was uncovered that the retarded GC progression mediated by CPSF6 knockdown was reversed by IBSP overexpression. CONCLUSION: Our study highlighted the vital role of the CPSF6/IBSP axis in GC, suggesting that IBSP might be an effective bio-target for GC treatment.
RESUMO
In the present study, we introduced the H 2O 2-sensitive thiazolidinone moiety at the 4th amino group of gemcitabine (GEM) to synthesize a new target compound named GEM-ZZQ, and then we confirmed its chemical structure by nuclear magnetic resonance spectroscopy. We further confirmed that GEM-ZZQ had a good chemical stability in different pH solutions in vitro and that it could be activated by H 2O 2 to release GEM. Pharmacodynamic studies revealed that the growth inhibition of human normal epithelial cells was weaker by GEM-ZZQ than by GEM treatment and that the inhibition of various lung cancer cell lines by GEM-ZZQ was similar to that of GEM. For the lung cancer cell lines that are resistant to the epidermal growth factor receptor (EGFR)-targeting inhibitor osimertinib, GEM-ZZQ showed less growth inhibition than GEM; however, GEM-ZZQ in combination with cisplatin showed better synergistic effects than GEM in the low-dose groups. In summary, we provided a new anti-cancer compound GEM-ZZQ for treating lung cancer by modifying the GEM structure.
RESUMO
Background: EDIL3, which contains epidermal growth factor-like repeats and discoidin I-like domains, is a secretory protein that plays an important role in embryonic development and various illnesses. However, the biological function of EDIL3 in gastric cancer (GC) is still unclear. The objective of this research was to explore the role and potential mechanism of EDIL3 in GC. Methods: In this study, we used the GEPIA, HPA, MethSurv, SMART, STRING, GeneMANIA, LinkedOmics TIMER, TIMER2.0, TISIDB, and RNAactDrug databases to comprehensively analyze the roles of EDIL3 in GC. To validate the in silico findings, EDIL3 expression was measured in our collected GC tissues. Meanwhile, several in vitro experiments were performed to test the function of EDIL3 in GC. Results: We found that EDIL3 was highly expressed in GC and associated with adverse clinical features. In vitro assays revealed that EDIL3 promoted the proliferation, migration, and invasion of GC cells. The functions of EDIL3 and co-expression genes were significantly associated with extracellular structure organization and matrix receptor interaction. EDIL3 expression was positively associated with numerous tumor-infiltrating immune cells and their biomarkers. Conclusion: This study determined that EDIL3 may function as an oncogene and is associated with immune infiltration in GC. EDIL3 could be used as a potential therapeutic target for GC.
Assuntos
Proteínas de Ligação ao Cálcio , Neoplasias Gástricas , Humanos , Proteínas de Ligação ao Cálcio/metabolismo , Neoplasias Gástricas/genética , Prognóstico , Moléculas de Adesão Celular/metabolismoRESUMO
MMP-2 has been reported as the most validated target for cancer progression and deserves further investigation. However, due to the lack of methods for obtaining large amounts of highly purified and bioactive MMP-2, identifying specific substrates and developing specific inhibitors of MMP-2 remains extremely difficult. In this study, the DNA fragment coding for pro-MMP-2 was inserted into plasmid pET28a in an oriented manner, and the resulting recombinant protein was effectively expressed and led to accumulation as inclusion bodies in E. coli. This protein was easy to purify to near homogeneity by the combination of common inclusion bodies purification procedure and cold ethanol fractionation. Then, our results of gelatin zymography and fluorometric assay revealed that pro-MMP-2 at least partially restored its natural structure and enzymatic activity after renaturation. We obtained approximately 11 mg refolded pro-MMP-2 protein from 1 L LB broth, which was higher than other strategies previously reported. In conclusion, a simple and cost-effective procedure for obtaining high amounts of functional MMP-2 was developed, which would contribute to the progress of studies on the gamut of biological action of this important proteinase. Furthermore, our protocol should be appropriate for the expression, purification, and refolding of other bacterial toxic proteins.
Assuntos
Escherichia coli , Metaloproteinase 2 da Matriz , Escherichia coli/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/química , Proteínas Recombinantes/química , Proteínas de Bactérias/metabolismo , Corpos de Inclusão/química , Dobramento de Proteína , Redobramento de ProteínaRESUMO
Oxidative stress is an important pathogenic factor in ulcerative colitis (UC) and colitis-associated colorectal cancer (CAC), further impairing the entire colon. Intestinal epithelial cells (IECs) are crucial components of innate immunity and play an important role in maintaining intestinal barrier function. Recent studies have indicated that microRNA-222-3p (miR-222-3p) is increased in colon of UC and colorectal cancer (CRC) patients, and miR-222-3p is a crucial regulator of oxidative stress. However, whether miR-222-3p influences IEC oxidative stress in UC and CAC remains unknown. This study investigated the effect of miR-222-3p on the regulation of IEC oxidative stress in UC and CAC. An in vitro inflammation model was established in NCM460 colonic cells, mouse UC and CAC models were established in vivo, and IECs were isolated. The biological role and mechanism of miR-222-3p-mediated oxidative stress in UC and CAC were determined. We demonstrated that miR-222-3p expression was notably increased in dextran sulfate sodium (DSS)-induced NCM460 cells and IECs from UC and CAC mice. In vitro, these results showed that the downregulation of miR-222-3p reduced oxidative stress, caspase-3 activity, IL-1ß and TNF-α in DSS-induced NCM460 cells. We further identified BRG1 as the target gene of miR-222-3p, and downregulating miR-222-3p alleviated DSS-induced oxidative injury via promoting BRG1-mediated activation Nrf2/HO-1 signaling in NCM460 cells. The in vivo results demonstrated that inhibiting miR-222-3p in IECs significantly relieved oxidative stress and inflammation in the damaged colons of UC and CAC mice, as evidenced by decreases in ROS, MDA, IL-1ß and TNF-α levels and increases in GSH-Px levels. Our study further demonstrated that inhibiting miR-222-3p in IECs attenuated oxidative damage by targeting BRG1 to activate the Nrf2/HO-1 signaling. In summary, inhibiting miR-222-3p in IECs attenuates oxidative stress by targeting BRG1 to activate the Nrf2/HO-1 signaling, thereby reducing colonic inflammation and tumorigenesis.
Assuntos
Colite Ulcerativa , Neoplasias Associadas a Colite , MicroRNAs , Animais , Camundongos , Colite Ulcerativa/complicações , Colite Ulcerativa/genética , Colite Ulcerativa/metabolismo , Inflamação , MicroRNAs/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Booster immunizations and breakthrough infections can elicit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron subvariant neutralizing activity. However, the durability of the neutralization response is unknown. We characterize the sensitivity of BA.1, BA.2, BA.2.75, BA.4/BA.5, BF.7, BQ.1.1, and XBB against neutralizing antibodies from vaccination, hybrid immunity, and breakthrough infections 4-6 months after vaccination and infection. We show that a two-dose CoronaVac or a third-dose ZF2001 booster elicits limited neutralization against Omicron subvariants 6 months after vaccination. Hybrid immunity as well as Delta, BA.1, and BA.2 breakthrough infections induce long-term persistence of the antibody response, and over 70% of sera neutralize BA.1, BA.2, BA.4/BA.5, and BF.7. However, BQ.1.1 and XBB, followed by BA.2.75, are more resistant to neutralization, with neutralizing titer reductions of â¼9- to 41-fold, â¼16- to 63-fold, and â¼4- to 25-fold, respectively. These data highlight additional vaccination in CoronaVac- or ZF2001-vaccinated individuals and provide insight into the durability of neutralization against Omicron subvariants.
Assuntos
Infecções Irruptivas , COVID-19 , Humanos , COVID-19/prevenção & controle , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos AntiviraisRESUMO
AIMS: Exosomes are a subpopulation of extracellular vesicles (EV) derived from multivesicular body (MVB) that transmit various cellular molecular constituents, including long noncoding RNAs (lncRNAs), to promote intercellular communication. Our aim was to investigate the function and mechanism of exosomal LINC00355 in gastric cancer cells. MAIN METHODS: Exosomal levels of LINC00355 in GC patients and healthy controls were measured by RT-qPCR. The effects of exosomal LINC00355 on GC cell viability, proliferation, migration and invasion were evaluated by CCK8, colony formation, Transwell and wound healing assays. The expression levels of Ki67 in xenograft tumor tissues were confirmed by immunohistochemistry assay, and apoptosis was analyzed by TUNEL apoptosis assay. Western blotting was used to monitor protein expression. RNA immunoprecipitation and RNA pulldown were performed to detect the interaction between LINC00355 and HDAC3. Chromatin immunoprecipitation was used to assess the interaction of HDAC3 with the TP53INP1 promoter. KEY FINDINGS: Exosomal LINC00355 levels were higher in plasma from gastric cancer patients than in plasma from healthy volunteers. Exosomal LINC00355 promoted the proliferation, migration and invasion of gastric cancer cell lines. RNA sequence analysis demonstrated that LINC00355 knockdown downregulated histone deacetylase HDAC3 and upregulated TP53INP1. Mechanistic investigation indicated that exosomal LINC00355 interacted with HDAC3 to suppress TP53INP1 transcription, which promoted epithelial-mesenchymal transition (EMT). SIGNIFICANCE: Exosomal LINC00355 plays a pivotal role in regulating EMT to induce the malignant progression of GC. Exosomal LINC00355 could be a promising biomarker in the early diagnosis and prognosis of GC.
Assuntos
Exossomos , MicroRNAs , RNA Longo não Codificante , Neoplasias Gástricas , Humanos , Proteínas de Transporte/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Exossomos/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Choque Térmico/metabolismo , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , MicroRNAs/genética , RNA/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Neoplasias Gástricas/patologiaRESUMO
The FGF/FGFR signaling axis deregulation of the fibroblast growth factor receptor (FGFR) family is closely related to tumorigenesis, tumor progression and drug resistance to anticancer therapy. And fibroblast growth factor receptor 3 (FGFR3) is one member of this family. In this study, we aimed to investigate the effect of siRNA-induced knockdown of FGFR3 on the biological behaviors of intrahepatic cholangiocarcinoma (ICC). The expression levels of FGFR3 were determined in three intrahepatic cholangiocarcinoma cell lines RBE, HUCCT1 and HCCC9810 cell lines by Western blot. FGFR3 expression in RBE cell line was knocked down by siRNA. Our study found that knockdown of FGFR3 inhibited the migration, invasion and proliferation of ICC cells using Wound healing assay, Transwell migration and invasion assays and Cell proliferation assay. And significantly down-regulated the protein expression levels of MMP2, cyclinD1, and NCadherin, but had no significant effect on MMP9, cyclinD3, vimentin, E-cadherin protein. In addition, we found that ERK/c-Myc presumably is its signaling pathway by bioinformatics analysis and Western blot verification. To sum up, knockdown of FGFR3 inhibited the migration, invasion and proliferation of ICC cells. It demonstrated that FGFR3 probably becomes a therapeutic target for ICC and increases the proportion of potentially curable intrahepatic cholangiocarcinoma patients treated with FGFR inhibitors.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Humanos , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/metabolismo , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/farmacologia , Proliferação de Células/genética , Movimento Celular/genética , Colangiocarcinoma/patologia , RNA Interferente Pequeno/metabolismo , Ductos Biliares Intra-Hepáticos/patologia , Neoplasias dos Ductos Biliares/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão GênicaRESUMO
BACKGROUND: The emergence of SARS-CoV-2 Omicron subvariants has raised questions regarding resistance to immunity by natural infection or immunization. We examined the sensitivity of Delta and Omicron subvariants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4/5, and BA.3) to neutralizing antibodies from BBIBP-CorV-vaccinated and BBIBP-CorV- or ZF2001-boosted individuals, as well as individuals with Delta and BA.1 breakthrough infections, and determined their fusogenicity and infectivity. METHODS: In this cross-sectional study, serum samples from two doses of BBIBP-CorV-vaccinated individuals 1 (n = 36), 3 (n = 36), and 7 (n = 37) months after the second dose; BBIBP-CorV- (n = 25) or ZF2001-boosted (n = 30) individuals; and fully vaccinated individuals with Delta (n = 30) or BA.1 (n = 26) infection were collected. The serum-neutralizing reactivity and potency of bebtelovimab were assessed against D614G, Delta, and Omicron subvariants (BA.1, BA.1.1, BA.2, BA.2.12.1, BA.4/5, and BA.3) through a pseudovirus neutralization assay. The fusogenicity and infectivity of D614G, Delta, and Omicron subvariants were determined by cell-cell fusion assay and pseudovirus infection assay, respectively. RESULTS: Omicron subvariants markedly escaped vaccine-elicited neutralizing antibodies after two doses of BBIBP-CorV with comparable efficiency. A third dose vaccination of BBIBP-CorV or ZF2001 increased neutralizing antibody titers and breadth against Delta and three Omicron subvariants. Delta and BA.1 breakthrough infections induced comparable neutralizing antibody titers against D614G and Delta variants, whereas BA.1 breakthrough infections elicited a stronger and broader antibody response against three Omicron subvariants than Delta breakthrough infections. BA.2.12.1 and BA.4/5 are more resistant to immunity induced by breakthrough infections. Bebtelovimab had no significant loss of potency against the Delta and Omicron subvariants. Cell culture experiments showed Omicron subvariants to be less fusogenic and have higher infectivity than D614G and Delta with comparable efficiency. CONCLUSIONS: These findings have important public health implications and highlight the importance of repeated exposure to SARS-CoV-2 antigens to broaden the neutralizing antibody response against Omicron subvariants.
Assuntos
COVID-19 , Humanos , Estudos Transversais , SARS-CoV-2 , Anticorpos Neutralizantes , Infecções Irruptivas , Anticorpos AntiviraisRESUMO
The severe acute respiratory syndrome coronavirus 1 (SARS-CoV-1) survivors are more likely to produce a potent immune response to SARS-CoV-2 after booster vaccination. We assessed humoral and T cell responses against SARS-CoV-2 in previously vaccinated SARS-CoV-1 survivors and naïve healthy individuals (NHIs) after a booster Ad5-nCoV dose. Boosted SARS-CoV-1 survivors had a high neutralization of SARS-CoV-2 Wuhan-Hu-1 (WA1), Beta, and Delta but is limited to Omicron subvariants (BA.1, BA.2, BA.2.12.1, and BA.4/BA.5). Most boosted SARS-CoV-1 survivors had robust SARS-CoV-2-specific CD4+ and CD8+ T cell responses. While booster vaccination in NHIs elicited less or ineffective neutralization of WA1, Beta, and Delta, and none of them induced neutralizing antibodies against Omicron subvariants. However, they developed comparable SARS-CoV-2-specific T cell responses compared to boosted SARS-CoV-1 survivors. These findings suggest that boosted Ad5-nCoV would not elicit effective neutralizing antibodies against Omicron subvariants in SARS-CoV-1 survivors and NHIs but induced comparable robust T cell responses. Achieving a high antibody titer in SARS-CoV-1 survivors and NHIs is desirable to generate broad neutralization.
Assuntos
Vacinas contra a AIDS , COVID-19 , Vacinas contra Influenza , Vacinas contra Papillomavirus , Vacinas contra Vírus Sincicial Respiratório , Vacinas contra a SAIDS , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacina BCG , Vacinas contra COVID-19 , Vacina contra Difteria, Tétano e Coqueluche , Humanos , Vacina contra Sarampo-Caxumba-Rubéola , SARS-CoV-2 , SobreviventesRESUMO
PURPOSE: Intrahepatic cholangiocarcinoma (ICC) can invade and metastasize. EIF5A2 is involved in the invasive metastatic process of several digestive malignancies. However, its role in ICC is yet to be elucidated. METHODS: Immunohistochemistry (IHC) and Western blot (WB) were used to detect the level of EIF5A2 in the tumor specimens of ICC patients and evaluate the correlation between its expression and clinicopathological characteristics. The significance of EIF5A2 in the prognosis of ICC patients was further evaluated by Kaplan-Meier and Cox regression analysis. In addition, CCK-8, EdU, Transwell invasion, and scratch assays were utilized to detect tumor cell proliferation, invasion, and metastasis. Furthermore, the role of EIF5A2 in ICC cells was evaluated after modification of EIF5A2 expression. RESULTS: The level of EIF5A2 protein was significantly higher in ICC than in adjacent tissues. This high expression in the tumor samples was significantly associated with malignant phenotypes, such as lymph node metastasis (LNM), microvascular or bile duct invasion, and poor differentiation. ICC patients with high expression of EIF5A2 had short overall survival and a high cumulative recurrence rate. The multifactorial analysis showed that EIF5A2 is an independent prognostic marker. Furthermore, high levels of EIF5A2 may activate the PI3K/AKT/mTOR signaling pathway and upregulate Cyclin D1, Cyclin D3, MMP2, and MMP9 to promote ICC cell proliferation, migration, and invasion. CONCLUSION: The current study found that EIF5A2 promotes ICC progression and is a prognostic biomarker and candidate therapeutic target for ICC patients.