Corrigendum: Meta-analysis of the association between toll-like receptor gene polymorphisms and hepatitis C virus infection.

[This corrects the article DOI: 10.3389/fmicb.2023.1254805.].

Meta-analysis of the association between toll-like receptor gene polymorphisms and hepatitis C virus infection.

Objective: The objective of this study is to investigate the association between toll-like receptor (TLR) 3/7 gene polymorphisms and the infection by hepatitis C virus (HCV). Methods: PubMed, Embase, Web of Science, Scopus, CNKI, Wanfang Data, and SinoMed were searched to identify studies focusing on the association between the TLR3 rs3775290 or the TLR7 rs179008 single nucleotide polymorphisms (SNPs) and the HCV infection. All the related articles were collected from the inception of each database to 15 January 2023. Our meta-analysis was conducted using the allelic model, the dominant model, and the recessive model. Outcomes were presented by odds ratio (ORs) and 95% confidence interval (95%CI). The heterogeneity across studies was assessed by the I2 test. A subgroup analysis was performed to explore the source of heterogeneity. Funnel plots were drawn to assess the risk of publication bias. Review Manager 5.4 was used for statistical analysis. Results: Ten articles were finally included, among which six studies were analyzed for rs3775290 and five studies were analyzed for rs179008. Studies relating to rs3775290 included 801 patients and 1,045 controls, whereas studies relating to rs179008 included 924 patients and 784 controls. The results of the meta-analysis showed that there is no significant association between rs3775290 gene polymorphism and HCV infection (T vs. C: OR = 1.12, 95%CI 0.97-1.30; TT+CT vs. CC: OR = 1.20, 95%CI 0.73-1.96; TT vs. CT+CC: OR = 1.13, 95%CI 0.68-1.89). The recessive model showed that rs179008-T allele homozygotes had an 89% increased risk of infection by HCV compared with rs179008-A allele carriers (TT vs. AT+AA: OR = 1.89, 95%CI 1.13-3.16). The results of the subgroup analysis demonstrated that the characteristics of the control population may serve as an important source of heterogeneity. In the African populations, individuals with homozygous rs179008-T alleles had a higher risk of infection by HCV than rs179008-A allele carriers (OR = 2.14, 95%CI 1.18-3.87). We did not find that this difference existed in the European populations (OR = 1.24, 95%CI 0.43-3.56). Conclusion: There is no significant association between rs3775290 single nucleotide polymorphism and the infection by HCV. Individuals with homozygous rs179008-T alleles have a higher risk of an infection by HCV than rs179008-A allele carriers, which is statistically significant in the African populations.

Molecular docking of potential SARS-CoV-2 papain-like protease inhibitors.

SARS-CoV-2 papain-like protease is considered as an important potential target for anti-SARS-CoV-2 drug discovery due to its crucial roles in viral spread and innate immunity. Here, we have utilized an in silico molecular docking approach to identify the possible inhibitors of the SARS-CoV-2 papain-like protease, by screening 21 antiviral, antifungal and anticancer compounds. Among them, Neobavaisoflavone has the highest binding energy for SARS-CoV-2 papain-like protease. These molecules could bind near the SARS-CoV-2 papain-like protease crucial catalytic triad, ubiquitination and ISGylation residues: Trp106, Asn109, Cys111, Met208, Lys232, Pro247, Tyr268, Gln269, His272, Asp286 and Thr301. Because blocking the papain-like protease is an important strategy in fighting against viruses, these compounds might be promising candidates for therapeutic intervention against COVID-19.

ACE2 isoform diversity predicts the host susceptibility of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the ongoing coronavirus disease 2019 (COVID-19) pandemic. Angiotensin-converting enzyme 2 (ACE2) is the functional receptor for SARS-CoV-2. In our current study, we found that two types of deficient ACE2 isoforms from different mammals compete with full-length ACE2 for association with S protein. One type of ACE2 is a natural soluble isoform, the other type of ACE2 only associates with one loop of the receptor-binding domain (RBD) of the SARS-CoV-2 S protein. Mammals with either type of ACE2 will be deficient in support of SARS-CoV-2 entry. By combining S recognition and isoform analysis of ACE2, we predict that felids, mustelids, hamsters, and sheep are susceptible to SARS-CoV-2, while canids, swines, cattle, and goats are not permissive for SARS-CoV-2. Thus, the differential susceptibilities of mammals with SARS-CoV-2 infection could be partially explained by the ACE2 isoform diversity. Our findings will shed important light on predicting the host range of other zoonotic viruses.

SARS-CoV-2 spike protein favors ACE2 from Bovidae and Cricetidae.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes the recent COVID-19 public health crisis. Bat is the widely believed original host of SARS-CoV-2. However, its intermediate host before transmitting to humans is not clear. Some studies proposed pangolin, snake, or turtle as the intermediate hosts. Angiotensin-converting enzyme 2 (ACE2) is the receptor for SARS-CoV-2, which determines the potential host range for SARS-CoV-2. On the basis of structural information of the complex of human ACE2 and SARS-CoV-2 receptor-binding domain (RBD), we analyzed the affinity to S protein of the 20 key residues in ACE2 from mammal, bird, turtle, and snake. Several ACE2 proteins from Primates, Bovidae, Cricetidae, and Cetacea maintained the majority of key residues in ACE2 for associating with SARS-CoV-2 RBD. The simulated structures indicated that ACE2 proteins from Bovidae and Cricetidae were able to associate with SARS-CoV-2 RBD. We found that nearly half of the key residues in turtle, snake, and bird were changed. The simulated structures showed several key contacts with SARS-CoV-2 RBD in turtle and snake ACE2 were abolished. This study demonstrated that neither snake nor turtle was the intermediate hosts for SARS-CoV-2, which further reinforced the concept that the reptiles are resistant against infection of coronavirus. This study suggested that Bovidae and Cricetidae should be included in the screening of intermediate hosts for SARS-CoV-2.

Spike protein recognition of mammalian ACE2 predicts the host range and an optimized ACE2 for SARS-CoV-2 infection.

SARS-CoV-2 causes the recent global COVID-19 public health emergency. ACE2 is the receptor for both SARS-CoV-2 and SARS-CoV. To predict the potential host range of SARS-CoV-2, we analyzed the key residues of ACE2 for recognizing S protein. We found that most of the selected mammals including pets (dog and cat), pangolin and Circetidae mammals remained the most of key residues for association with S protein from SARS-CoV and SARS-CoV-2. The interaction interface between cat/dog/pangolin/Chinese hamster ACE2 and SARS-CoV/SARS-CoV-2 S protein was simulated through homology modeling. We identified that N82 in ACE2 showed a closer contact with SARS-CoV-2 S protein than M82 in human ACE2. Our finding will provide important insights into the host range of SARS-CoV-2 and a new strategy to design an optimized ACE2 for SARS-CoV-2 infection.

SR-BI Interactome Analysis Reveals a Proviral Role for UGGT1 in Hepatitis C Virus Entry.

Hepatitis C virus (HCV) entry is mediated by multiple co-receptors including scavenger receptor class B, type I (SR-BI). To elucidate the interactome of human SR-BI, we performed immunoprecipitation (IP) experiment coupled with mass spectrometry (MS) analysis. UDP-glucose:glycoprotein glucosyltransferase 1 (UGGT1), a key component of calnexin cycle involved in protein glycosylation, was identified as a SR-BI-interacting protein. Silencing UGGT1 or N-glycosylation inhibitor treatment reduced SR-BI protein level. Further study demonstrated that human SR-BI was N-glycosylated at nine asparagines. Moreover, HCV entry and infection were reduced by the absence of UGGT1. Interestingly, silencing SR-BI reduced protein stability of UGGT1 and protein quality control function mediated by UGGT1. Our finding not only identified UGGT1 as a HCV host factor, but also identified a UGGT1-mediated protein folding function for SR-BI.

Anticancer Effects of Constituents of Herbs Targeting Osteosarcoma.

Osteosarcoma is a rare primary malignancy of bone that is prone to early metastasis. Resection surgery and chemotherapeutic regimens are current standard treatments for osteosarcoma. However, the long-term survival rate of patients with osteosarcoma is low due to a high risk of metastasis. Hence, a new approach is urgently needed to improve the treatment of osteosarcoma. Compared with chemotherapy, natural active constituents isolated from herbs exhibit less adverse effects and better anti-tumor effects. This study aimed to summarize the anticancer effects of constituents of herbs on the progression and metastasis of osteosarcoma cells. It showed that many constituents of herbs inhibited osteosarcoma by targeting proliferation, matrix metalloproteinases, integrin and cadherin, and angiogenesis. The findings might be beneficial for the development of new drugs and treatment strategies.

The Expression of SOCS and NF-Ï°B p65 in Hypopharyngeal Carcinoma.

BACKGROUND: Hypopharyngeal carcinoma is one of the most common types of head and neck tumors. Suppressers of cytokine signalling (SOCS) family members are key regulators of cytokine homeostasis, they play important roles in the process of cell proliferation, differentiation, maturation and apoptosis, and participate in the occurrence and development of tumor. The abnormal activation of NF-Ï°B is an important feature of the tumor. The aim of this study was to investigate the relationships among SOCS, NF-Ï°B p65 and hypopharyngeal carcinoma development.C. METHODS: We included 72 hypopharyngeal cancer patients and 9 swallow cyst patients. The patients were recruited at The Second Hospital of Shandong University (Jinan, China) between 2014 and 2016. The mRNA and protein expression levels of SOCS-1, SOCS-3 and NF-Ï°B p65 in hypopharyngeal carcinoma tissues, para-cancerous tissues and control tissues were detected by RT-PCR and Western blot analysis, respectively. RESULTS: Hypopharyngeal carcinoma tissues had lower level expression of SOCS-1 and SOCS-3 than pericarcinoma tissues, but there was no significant difference, while cancer tissues had significantly higher level expression of NF-Ï°B p65 than that of pericarcinoma tissues (0.412±0.266, 0.281±0.231, t=2.969, P=0.004). The early stage patients had striking higher level expression of SOCS-1 and SOCS-3 than that in advanced stages (F=16.202, P<0.001; F=52.295, P<0.001), while the expression of NF-Ï°B p65 in early stages had lower level than that in advanced stages (F=3.383, P=0.04). CONCLUSION: SOCS-1, SOCS-3 may be protective factors while NF-Ï°B p65 could be a harmful factor in hypopharyngeal carcinoma.

MicroRNA-181 as a prognostic biomarker for survival in acute myeloid leukemia: a meta-analysis.

Accumulating evidence has indicated that microRNA-181 (miR-181) is dysregulated in hematological malignancies, and associates with the clinical outcomes. However, the association of miR-181 expression levels with acute myeloid leukemia (AML) remains inconclusive, as publications from different groups have reported contradictory results. In this manuscript, a meta-analysis was performed to assess the prognostic significance of miR-181 in AML patients. Eligible studies were retrieved from PubMed, Embase and Cochrane Library databases, and a total of 6 studies including 815 AML patients were included in the final analysis. Hazard ratios (HRs) and their corresponding 95% confidence intervals (CIs) were extracted and pooled to investigate the correlation between miR-181 and the survival of AML patients. Our results showed that elevated miR-181 expression was associated with increased survival in 395 American patients, and reduced survival in 325 Chinese patients. Both subgroup analyses and meta-regression indicated that the origin of AML patients contributed to the heterogeneity in the datasets evaluating the correlation between overall survival (OS) and miR-181. These results indicate that miR-181 can be used as a promising prognostic biomarker in AML patients, which may depend on the origin of patient population.

Expression of Th1- Th2- and Th17-associated cytokines in laryngeal carcinoma.

T-helper (Th) 0 cell differentiation into Th1 or Th2 cells is dependent on a number of transcription factors that act at specific time points to regulate gene expression. Th17 cells, a subset of interleukin (IL)-17-producing T cells distinct from Th1 or Th2 cells, are considered to exhibit a critical function in inflammation and autoimmune diseases, as well as cancer development. In the present study, the expression of Th1-, Th2- and Th17-associated cytokines in laryngeal cancer and pericarcinoma tissues obtained from 57 laryngeal carcinoma patients was investigated. The association between Th1, Th2 and Th17 infiltration and tumor development was also evaluated. Reverse transcription-polymerase chain reaction and western blotting results revealed that the mRNA and protein expression of Th2 cytokines was lower, while the expression of Th1 and Th17 cytokines was higher in tumor tissues than in pericarcinoma tissues. Furthermore, the early stage cancer patients exhibited a higher level of interferon-γ, IL-2 and IL-17 mRNA expression than those at advanced stages. Cancer tissues exhibited higher Th17 cytokine expression than pericarcinoma tissues. By contrast, Th1 cytokine expression was increased in pericarcinoma tissues compared with cancer tissues. These results indicate that high expression of Th1- and Th17-associated cytokines in laryngeal carcinoma may contribute to suppression of cancer development and a relatively good prognosis.

miR-373 Inhibits Glioma Cell U251 Migration and Invasion by Down-Regulating CD44 and TGFBR2.

Glioblastoma multiforme (GBM) is the most malignant glioma, unveiling the underlying mechanisms of its aggressiveness could promote the discovery of potential targets for effective treatment. MicroRNAs (miRNAs) are important participants in both development and disease, its involvement in cancers has long been recognized. In this study, we investigated the role of miRNA-373 (miR-373) in GBM cell line U251, demonstrated that although miR-373 does not affect cell growth of U251, it inhibits migration and invasion of U251. Forced expression of miR-373 down-regulates the expressions CD44 and TGFBR2, while knockdown of CD44 and TGFBR2 presents the similar phenotype as miR-373 overexpression, suggesting that CD44 and TGFBR2 are functional targets of miR-373, down-regulation of CD44 and TGFBR2 by miR-373 are partly responsible for the migration, and invasion suppressive role of miR-373 in U251.

Meta-analysis of the differentially expressed microRNA profiles in nasopharyngeal carcinoma.

MicroRNAs(miRNAs), as non-coding molecules, were proved to be correlated with gene expression in naspharyngeal carcinoma (NPC) development. In this research, a comprehensive meta-analysis of eight independent miRNA expression studies in NPC was preformed by using robust rank aggregation method (RRA), which contained a total of 775 tumor and 227 non-cancerous samples. There were 7 significant dysregulated miRNAs identified including three increased (miR-483-5p, miR-29c-3p and miR-205-5p) and four decreased (miR-29b-3p, let-7d-5p, miR-100- 5p and let-7g-5p) miRNAs. Subsequently, the miRNA target prediction and pathway enrichment analysis were carried out to find out the biological and functional relevant genes involved in the meta-signature miRNA regulation. Finally, several signaling and cancer pathogenesis pathways were suggested to be more frequently associated with the progression of NPC. In this research the meta-signature miRNA identified may be used to develop a series of diagnostic and prognostic biomarkers for NPC that serve specificity for use in clinics.

Th1-, Th2-, and Th17-associated cytokine expression in hypopharyngeal carcinoma and clinical significance.

Th0 cells differentiate into Th1 or Th2 depending on multiple transcription factors acting on specific time points to regulate gene expression. Th17 cells, a subset of IL-17-producing T cells distinct from Th1 or Th2 cells, have been described as key players in inflammation and autoimmune diseases as well as cancer development. In the present study, 53 patients with hypopharyngeal cancer were included. The expression levels of Th1-, Th2- and Th17-associated cytokines in hypopharyngeal cancer tissues and pericarcinoma tissues were detected. The relationship between Th1, Th2, or Th17 infiltration and metastasis was studied. Our results showed that the mRNA and protein expressions of Th1 cytokines were lower, while the expressions of Th2 and Th17 cytokines were higher in tumor tissues, and the intensity of expression was strengthened with clinical stage increasing. Cancer tissues had higher level expressions of Th2 and Th17 cytokines than that of pericarcinoma tissues. From the above data, we speculated that high expressions of Th2- and Th17-associated cytokines in hypopharyngeal carcinoma may contribute to cancer development and metastasis.

Mapping quantitative trait loci conferring resistance to rice black-streaked virus in maize (Zea mays L.).

Maize rough dwarf disease (MRDD) is one of the most serious virus diseases of maize worldwide, and it causes great reduction of maize production. In China, the pathogen was shown to be rice black-streaked virus (RBSDV). Currently, MRDD has spread broadly and leads to significant loss in China. However, there has been little research devoted to this disease. Our aims were to identify the markers and loci underlying resistance to this virus disease. In this study, segregation populations were constructed from two maize elite lines '90110', which is highly resistant to MRDD and 'Ye478', which is highly susceptible to MRDD. The F(2) and BC(1) populations were used for bulk sergeant analysis (BSA) to identify resistance-related markers. One hundred and twenty F(7:9) RILs were used for quantitative trait loci (QTL) mapping through the experiment of multiple environments over 3 years. Natural occurrence and artificial inoculation were both used and combined to determine the phenotype of plants. Five QTL, qMRD2, qMRD6, qMRD7, qMRD8 and qMRD10 were measured in the experiments. The qMRD8 on chromosome 8 was proved to be one major QTL conferring resistance to RBSDV disease in almost all traits and environments, which explained 12.0-28.9 % of the phenotypic variance for disease severity in this present study.