Osong Public Health and Research Perspectives

Original Articles

The value of CDC42 effector protein 2 as a novel prognostic biomarker in liver hepatocellular carcinoma: a comprehensive data analysis: Hye-Ran Kim, Choong Won Seo, Jongwan Kim; Osong Public Health Res Perspect. 2023;14(6):451-467. Published online December 15, 2023; DOI: https://doi.org/10.24171/j.phrp.2023.0229

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The prognostic significance of CDC42 effector protein 2 (CDC42EP2) and its association with tumor-infiltrating immune cells (TIICs) have not been explored in liver hepatocellular carcinoma (LIHC). This study aims to assess the potential prognostic value of CDC42EP2 by conducting a comprehensive analysis of online databases pertaining to LIHC. Methods: We evaluated the potential of CDC42EP2 as a prognostic biomarker by utilizing online databases such as TIMER, GEPIA2, KM, OSlihc, HPA, and LinkedOmics. Results: In LIHC, we observed that the mRNA and protein expression of CDC42EP2 were upregulated compared to normal tissues. Upregulated CDC42EP2 expression was associated with a worse prognosis based on the clinicopathological characteristics of patients with LIHC. Furthermore, CDC42EP2 was positively associated with TIICs. In the co-expression and functional enrichment analyses of CDC42EP2, 11,416 genes showed positive associations with CDC42EP2 while 8,008 genes showed negative associations. CDC42EP2-related co-expression genes were involved in protein localization to the endoplasmic reticulum, translational initiation, and RNA catabolic processes in gene set enrichment analysis-Gene Ontology (GSEAGO), and regulated the ribosome, spliceosome, and primary immune deficiency in the GSEAKyoto Encyclopedia of Genes and Genomes (KEGG) pathway. In a survival map, 23 and 17 genes that exhibited positive associations with CDC42EP2 showed a significant hazard ratio (HR) for overall survival and disease-free survival, respectively. Conclusion: Our findings demonstrated that CDC42EP2 is a novel prognostic biomarker and a potential tumor immune therapeutic target in patients with LIHC.

Genetic diversity and evolutionary patterns of SARS-CoV-2 among the Bhutanese population during the pandemic: Tshering Dorji, Kunzang Dorji, Tandin Wangchuk, Tshering Pelki, Sonam Gyeltshen; Osong Public Health Res Perspect. 2023;14(6):494-507. Published online December 14, 2023; DOI: https://doi.org/10.24171/j.phrp.2023.0209

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Graphical Abstract Abstract PDF: Objectives
The coronavirus disease 2019 (COVID-19) pandemic, caused by a dynamic virus, has had a profound global impact. Despite declining global COVID-19 cases and mortality rates, the emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants remains a major concern. This study provides a comprehensive analysis of the genomic sequences of SARS-CoV-2 within the Bhutanese population during the pandemic. The primary aim was to elucidate the molecular epidemiology and evolutionary patterns of SARS-CoV-2 in Bhutan, with a particular focus on genetic variations and lineage dynamics. Methods: Whole-genome sequences of SARS-CoV-2 collected from Bhutan between May 2020 and February 2023 (n=135) were retrieved from the Global Initiative on Sharing All Influenza Database. Results: The SARS-CoV-2 variants in Bhutan were predominantly classified within the Nextstrain clade 20A (31.1%), followed by clade 21L (20%) and clade 22D (15.6%). We identified 26 Pangolin lineages with variations in their spatial and temporal distribution. Bayesian time-scaled phylogenetic analysis estimated the time to the most recent common ancestor as February 15, 2020, with a substitution rate of 0.97×10–3 substitutions per site per year. Notably, the spike glycoprotein displayed the highest mutation frequency among major viral proteins, with 116 distinct mutations, including D614G. The Bhutanese isolates also featured mutations such as E484K, K417N, and S477N in the spike protein, which have implications for altered viral properties. Conclusion: This is the first study to describe the genetic diversity of SARS-CoV-2 circulating in Bhutan during the pandemic, and this data can inform public health policies and strategies for preventing future outbreaks in Bhutan.

Phylogenetic and genome-wide mutational analysis of SARS-CoV-2 strains circulating in Nigeria: no implications for attenuated COVID-19 outcomes: Daniel B. Kolawole, Malachy I. Okeke; Osong Public Health Res Perspect. 2022;13(2):101-113. Published online April 22, 2022; DOI: https://doi.org/10.24171/j.phrp.2021.0329

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Graphical Abstract Abstract PDF: Objectives
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19). The COVID-19 incidence and mortality rates are low in Nigeria compared to global trends. This research mapped the evolution of SARS-CoV-2 circulating in Nigeria and globally to determine whether the Nigerian isolates are genetically distinct from strains circulating in regions of the world with a high disease burden. Methods: Bayesian phylogenetics using BEAST 2.0, genetic similarity analyses, and genomewide mutational analyses were used to characterize the strains of SARS-CoV-2 isolated in Nigeria. Results: SARS-CoV-2 strains isolated in Nigeria showed multiple lineages and possible introductions from Europe and Asia. Phylogenetic clustering and sequence similarity analyses demonstrated that Nigerian isolates were not genetically distinct from strains isolated in other parts of the globe. Mutational analysis demonstrated that the D614G mutation in the spike protein, the P323L mutation in open reading frame 1b (and more specifically in NSP12), and the R203K/ G204R mutation pair in the nucleocapsid protein were most prevalent in the Nigerian isolates. Conclusion: The SARS-CoV-2 strains in Nigeria were neither phylogenetically nor genetically distinct from virus strains circulating in other countries of the world. Thus, differences in SARS-CoV-2 genomes are not a plausible explanation for the attenuated COVID-19 outcomes in Nigeria.

Review Article

Yersinia pestis antibiotic resistance: a systematic review: Chen Lei, Suresh Kumar; Osong Public Health Res Perspect. 2022;13(1):24-36. Published online February 18, 2022; DOI: https://doi.org/10.24171/j.phrp.2021.0288

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Abstract PDF

Yersinia pestis, the cause of plague and a potential biological weapon, has always been a threatening pathogen. Some strains of Y. pestis have varying degrees of antibiotic resistance. Thus, this systematic review was conducted to alert clinicians to this pathogen’s potential antimicrobial resistance. A review of the literature was conducted for experimental reports and systematic reviews on the topics of plague, Y. pestis, and antibiotic resistance. From 1995 to 2021, 7 Y. pestis isolates with 4 antibiotic resistance mechanisms were reported. In Y. pestis 17/95, 16/95, and 2180H, resistance was mediated by transferable plasmids. Each plasmid contained resistance genes encoded within specific transposons. Strain 17/95 presented multiple drug resistance, since plasmid 1202 contained 10 resistance determinants. Strains 16/95 and 2180H showed single antibiotic resistance because both additional plasmids in these strains carried only 1 antimicrobial determinant. Strains 12/87, S19960127, 56/13, and 59/13 exhibited streptomycin resistance due to an rpsl gene mutation, a novel mechanism that was discovered recently. Y. pestis can acquire antibiotic resistance in nature not only via conjugative transfer of antimicrobial-resistant plasmids from other bacteria, but also by gene point mutations. Global surveillance should be strengthened to identify antibiotic-resistant Y. pestis strains by whole-genome sequencing and drug susceptibility testing.

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Original Articles

Genome-Wide Identification and Characterization of Point Mutations in the SARS-CoV-2 Genome: Jun-Sub Kim, Jun-Hyeong Jang, Jeong-Min Kim, Yoon-Seok Chung, Cheon-Kwon Yoo, Myung-Guk Han; Osong Public Health Res Perspect. 2020;11(3):101-111. Published online May 14, 2020; DOI: https://doi.org/10.24171/j.phrp.2020.11.3.05

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Abstract PDF

Objectives

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in Wuhan, China, in December 2019 and has been rapidly spreading worldwide. Although the causal relationship among mutations and the features of SARS-CoV-2 such as rapid transmission, pathogenicity, and tropism, remains unclear, our results of genomic mutations in SARS-CoV-2 may help to interpret the interaction between genomic characterization in SARS-CoV-2 and infectivity with the host.

Methods

A total of 4,254 genomic sequences of SARS-CoV-2 were collected from the Global Initiative on Sharing all Influenza Data (GISAID). Multiple sequence alignment for phylogenetic analysis and comparative genomic approach for mutation analysis were conducted using Molecular Evolutionary Genetics Analysis (MEGA), and an in-house program based on Perl language, respectively.

Results

Phylogenetic analysis of SARS-CoV-2 strains indicated that there were 3 major clades including S, V, and G, and 2 subclades (G.1 and G.2). There were 767 types of synonymous and 1,352 types of non-synonymous mutation. ORF1a, ORF1b, S, and N genes were detected at high frequency, whereas ORF7b and E genes exhibited low frequency. In the receptor-binding domain (RBD) of the S gene, 11 non-synonymous mutations were observed in the region adjacent to the angiotensin converting enzyme 2 (ACE2) binding site.

Conclusion

It has been reported that the rapid infectivity and transmission of SARS-CoV-2 associated with host receptor affinity are derived from several mutations in its genes. Without these genetic mutations to enhance evolutionary adaptation, species recognition, host receptor affinity, and pathogenicity, it would not survive. It is expected that our results could provide an important clue in understanding the genomic characteristics of SARS-CoV-2.

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Comparison of Three Different Methods for Detection of IL28 rs12979860 Polymorphisms as a Predictor of Treatment Outcome in Patients with Hepatitis C Virus: Abolfazl Fateh, Mohammadreza Aghasadeghi, Seyed D. Siadat, Farzam Vaziri, Farzin Sadeghi, Roohollah Fateh, Hossein Keyvani, Alireza H. Tasbiti, Shamsi Yari, Angila Ataei-Pirkooh, Seyed H. Monavari; Osong Public Health Res Perspect. 2016;7(2):83-89. Published online April 30, 2016; DOI: https://doi.org/10.1016/j.phrp.2015.11.004

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Abstract PDF

Objectives
This study aimed to evaluate the specificity, sensitivity, cost, and turn-around time of three methods of gene polymorphism analysis and to study the relationship between IL28B rs12979860 and SVR rate to pegIFN-α/RVB therapy among patients with chronic hepatitis C.
Methods
A total of 100 samples from chronic hepatitis C patients were analyzed in parallel using the three methods: direct sequencing, real-time polymerase chain reaction (PCR), amplification refractory mutation system (ARMS)-PCR.
Results
The different profiles for IL28B rs12979860 alleles (CC, CT, and TT) obtained with PCR-RFLP, ARMS-PCR, and direct sequencing were consistent among the three methods. Prevalence of rs12979860 genotypes CC, CT and TT in HCV genotype 1a was 10(19.6%), 35(68.6%), and six (11.8%), respectively, and in HCV genotype 31, it was 13(26.5%), 31(63.3%), and five (10.2%), respectively. No significant difference was seen between rs12979860 genotype and HCV genotype (p = 0.710).
Conclusion
Screening by ARMS – PCR SNOP detection represents the most efficient and reliable method to determine HCV polymorphisms in routine clinical practice.

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Infectivity of Homologous Recombinant HIV-1 Pseudo-virus with Reverse Transcriptase Inhibitor-related Mutations from Highly Active Antiretroviral Therapy Experienced Patients: Oh-Kyung Kwon, Ju-yeon Choi, Eun-Jin Kim, Sung Soon Kim; Osong Public Health Res Perspect. 2011;2(1):23-28. Published online June 30, 2011; DOI: https://doi.org/10.1016/j.phrp.2011.04.006

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Abstract PDF

Objectives
In this study, the viral fitness of pseudo-viruses with a drug-resistant site in the reverse transcriptase (RT) region of the genome was investigated. The pseudo-viruses were derived from highly active antiretroviral therapy (HAART)-experienced HIV/AIDS patients.
Methods
HIV-1 RNA was extracted from the plasma of HAART-experienced (KRB9149, KRB7021, KRC1097) and HAART-naïve (KRC5180, KRC5123) HIV-1 patients. The RT gene from the extracted viral RNA was amplified and the polymerase chain reaction product was cloned from the pHXB2Δ2-261 RT vector. C8166 and TZM-bl cell lines were used as the HIV-1 replication capacity measurement system. To quantify the infectivity of homologous recombinant HIV-1, the infectivity derived from each pseudo-virus was compared with the infectivity of the reference strain HXB2.
Results
Patient-derived HIV-1 was cotransfected into C8166 cells and the expression level of the p24 antigen was measured. The expression was high in the HIV-1 isolates from patients KRC5180 and KRB9149 and low in patients KRB7021, KRC5123, and KRC1097, when compared with the reference strain. The infectivity of the pseudo-virus measured in TZM-bl cells decreased in the order, reference strain HXB2 > KRC5180 > KRC5123 > KRB9149 > KRB7021 > KRC1097.
Conclusion
In this study, HIV-1 infectivity of the drug-resistant strain isolated from HAART-experienced patients with HIV/AIDS was found to be lower than the infectivity of the reference strain HXB2. This study provides useful data for the phenotypic susceptibility assay in HAART-experienced patients infected with HIV-1.

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