Current Proteomics - Volume 20, Issue 1, 2023

Background: The advancement of proteomics studies leads to various benefits in research. However, in Malaysia, proteomics studies are still in their early stage. Objective: Four adult Pulchrana glandulosa individuals were collected from the stream of Temurun Waterfall for their proteomics information. Methods: These frogs’ skin secretions were collected, extracted, and analysed for their protein antimicrobial peptide compounds and biomedical potentials using liquid chromatography-mass spectrometry. Results: Forty-six proteins had been identified from the skin secretion of this species. They contained unreviewed proteins, enzymes, AMPs, receptors, regulatory, transport, hormone, and developmental proteins. In addition, 11 AMP had been identified, consisting of esculentin-2, brevinin 1, and other AMPs. Conclusion: These proteins and AMPs have a wide range of biomedical importance, such as antimicrobials, anti-tumour, anti-cancerous, anti-viral, wound healing, anti-inflammation, anti-ageing and maintaining homeostasis.

Background: Leukocytes are key cellular effectors of inflammation in asthma and understanding their function in this disease is of crucial importance. Blood leukocytes reflect the actions of their counterparts in the lungs and they can be obtained through minimal invasive procedures as part of the peripheral blood. Objective: The aim of the study was to identify proteins in blood leukocyte proteomes that respond to ex vivo treatment by prednisone in order to pinpoint candidates for predictive biomarkers in corticosteroid- responsive asthma. Methods: The study included five children diagnosed with asthma and five healthy children. After the ex vivo treatment of blood samples with prednisone, lysis of erythrocytes was performed and proteins were extracted from the remaining leukocytes by ultrasonic disintegration. Protein extracts were analyzed by reversed phase nano-liquidchromatography–tandem mass spectrometry (LC–MS/MS). Results: The stimulation of asthmatics' leukocytes with prednisone has led to an increase in the levels of FYB (fold change 3.4) and LYZ (fold change 2.2) with a statistical significance of p<0.005. The two proteins with expressions significantly altered upon the prednisone treatment should be further explored as tools to evaluate the patient's response before therapy administration, especially when lung function measurements are not possible, as is the case with young pediatric patients. Conclusion: The approach that entails ex vivo response of blood leukocytes to therapeutics can facilitate asthma management and help overcome the need for therapeutic adjustments in a clinical setting.

Background: Such factors as diabetes and obesity can dramatically worsen COVID-19 symptoms. In addition, macrophage accumulation in adipose tissue is related to obesity. Therefore, macrophages play a significant role in raising COVID-19 susceptibility and severity in diabetes and obese patients. Methods: In this study, the functional impact of SARS-CoV-2 ORF7a on macrophages was analyzed using a domain-searching bioinformatics technique. Ca2+ binding domain, kinase and phosphatase, SMB/SRCR, LBP/BPI/CETP, ABC, TIR,PARP, Flavivirus Cap enzyme, Cyclin, and other domains have been identified in SARS-CoV-2 ORF7a. ORF7a binds to oxidized low-density lipoprotein cholesterol particles by the macrophage receptor-like domains such as SMB/SRCR and enters macrophages via macropinocytosis. Then, ORF7a prevents 18 S rRNA maturation and adds flavivirus cap 0/1/2 to mRNA to interfere with transcription and translation via PARP, Flavivirus Cap enzyme, and other associated domains. Results: ORF7a activates and promotes G2/M phase transition via cyclin-related enzymatic activity domains. Conclusion: The destructive activity of ORF7a hijacks the nitric oxide release pathway of macrophages and promotes macrophage death, enabling the virus to elude the innate immune system and aggravate diabetes-related problems in patients.

Background: Clear cell renal cell carcinoma (ccRCC) is the most common type of kidney cancer, and it is a significant global health problem causing significant morbidity and mortality. Long noncoding RNAs (lncRNAs) have been identified as a class of gene expression regulators that play a critical role in the immune system. However, the function of lncRNAs in the immune microenvironment of ccRCC remains unclear. Methods: The least absolute shrinkage and selection operator regression techniques, robust likelihoodbased survival modeling, and Cox regression analysis were used to identify potential prognostic lncRNAs. The relationship between the signature and the tumor's immune infiltration was analyzed using gene set enrichment analysis and the subset analysis of immune cells. Results: LINC00839, LINC01671, AC093673, and AC008760 were selected to create a risk signature. For 3-, 5-, and 8-year overall survival rates, the areas under the receiver operating characteristic curves of the risk signature set were 0.689, 0.721, and 0.719 in the training set and 0.683, 0.686, and 0.665 in the validation set, respectively. A model and nomogram were constructed using the risk signature and clinical characteristics. The C-index of the model was 0.78 in the training set and 0.773 in the validation set. Conclusion: The risk signature reflects the tumor's current immune infiltration and is associated with regulatory T cell differentiation, interleukin 17 production regulation, negative regulation of inflammatory response to an antigenic stimulus, and the IL6-JAK-STAT3 signaling pathway. This study provides prognostic information for ccRCC patients and may also serve as a useful clue for future immunotherapies.

Background: Dental caries can affect the expression of salivary proteins. Proteomics allows us to analyze and identify many proteins in a single sample and experiment; bioinformatics is essential to analyze proteomic data. Objective: This research aims to identify and integrate the main differentially expressed proteins in the saliva of children with caries, infer their Gene Ontology and interactions, and identify regulatory factors. Materials and Methods: We extracted proteins from a bibliographic search in the Scopus and PubMed databases. We analyzed these proteins with the web application ShinyGO v0.76, ToppGene and NetworkAnalyst 3.0, and the Cytoscape platform. Results: In the literature search, we extracted 26 differentially expressed proteins. These proteins show enrichment in antioxidant activity, antimicrobial response, immune response, and vitamin and mineral metabolism. We found three transcription factors that regulate most of the genes of these proteins: TFDP1, SOX13, and BCL6. We also identified three microRNAs that highly restrict the expression of these proteins: hsa-mir-124-3p, hsa-mir-27a-3p, and hsa-mir-26b-5p. On the other hand, the main drugs associated with these proteins are potassium persulfate, aluminum, and cadmium. Conclusion: The differentially expressed proteins in the saliva of children with dental caries are involved in metabolic pathways related to folate, selenium, and vitamin B12 metabolism. In addition, some transcription factors (TFDP1, SOX13, and BCL6) miRNAs (hsa-mir-124-3p, hsa-mir-27a-3p, and hsa-mir-26b-5p) and chemical compounds (potassium persulfate, aluminum, and cadmium) can regulate the genes, mRNAs or proteins studied.

Background: S100 calcium-binding protein A11 (S100A11) has important roles in tumorigenesis and multiple cancer progression. Aims: In this study, we aimed to analyze the expression and prognostic value of S100A11 across cancers and further explore the relationship between S100A11 and the tumor immune microenvironment. Methods: We analyzed the differential expression of S100A11 in the TIMER, GEPIA, and BioGPS databases and searched for its prognostic impact in the GEPIA and Kaplan-Meier plotter databases. We used the SangerBox database to investigate the relationship between S100A11 expression and the tumor immune microenvironment. The TIMER database explored the relationship between S100A11 expression and tumor immune-infiltrated cells (TILs). Correlation analysis of S100A11 expression with clinical parameters in thyroid carcinoma (THCA) was performed using the UALCAN database. The co-expression network of S100A11 in THCA was explored through the LinkedOmics database. RT128;’qPCR and immunohistochemical (IHC) staining were used to analyze the expression level of S100A11 in THCA. Results: S100A11 expression was higher in many tumors than in paired normal tissues, and increased expression was associated with poor prognosis, including overall survival (OS), recurrence-free survival (RFS), and disease-free survival (DFS). S100A11 was differentially expressed in immune subtypes and molecular subtypes of some cancers. The expression of S100A11 was correlated with immune checkpoints (ICP), tumor mutational burden (TMB), microsatellite instability (MSI), neoantigens, and TILs. The methylation level of S100A11 was negatively correlated with mRNA expression. S100A11 expression had a specific correlation with the clinical parameters of THCA. In THCA, the coexpression network of S100A11 was mainly involved in regulating inflammation and immune responses. RT128;’qPCR and IHC staining confirmed that S100A11 was upregulated in THCA. Conclusion: S100A11 may be related to the regulation of the tumor microenvironment. S100A11 may serve as a potential pan-cancer biomarker for prognosis. S100A11 could be a potential target for THCA immunotherapy.

Background: Despite the crucial involvement of vitronectin in affecting the perseverance of certain respiratory pathogens and the progression of several lung diseases, the association of vitronectin with tuberculosis (TB) has been poorly studied. The present study aimed to determine whether vitronectin levels are altered in TB patients compared to healthy humans. Methods: Twenty-four laboratory-confirmed tuberculosis patients (pulmonary TB -8, extrapulmonary- 8 and HIV-TB dual infected -8) and eight healthy individuals were included in this study. The quantitative detection of vitronectin in serum-derived exosomes of study participants was performed using a sandwich enzyme-linked immunosorbent assay. Measured concentrations of vitronectin were compared with the demographic variables of the study participants and between the study groups. The Mann–Whitney U unpaired test was used in statistical analysis, and the p-value < 0.05 was considered statistically significant. Results: Vitronectin was detected in serum-derived exosomes of all study participants. The demographic characteristics (gender, age, smoking and alcohol consumption habit, history of cough, and weight loss) were not significantly correlated with the vitronectin concentrations of the study participants (p-value> 0.05). The level of vitronectin was higher in patients with pulmonary TB (778.54 ng/l) and extra-pulmonary-TB patients (773.04 ng/l) while lower in HIV-pulmonary TB dual-infected patients (354.86 ng/l) as compared to healthy humans (456.20ng/l). There was a significant difference between vitronectin concentrations of patients with pulmonary TB (p-value: 0.0002) and extrapulmonary TB (p-value: 0.003) compared to healthy controls. Conclusion: The present study reported an increased concentration of vitronectin in serum-derived exosomes of pulmonary and extra-pulmonary TB patients compared to HIV-TB dual-infected patients and healthy humans. Further studies are needed to fully elucidate the diagnostic potential and functionalities of higher concentrations of vitronectin in the pathogenic processes of human TB.

Following the publication of the original article [1], the authors reported that the complete grant number of the funding was omitted. In this correction, the incorrect and correct grant numbers are mentioned. The original publication of this article has been corrected. The funding acknowledgement published previously is as follows: The study was funded by Fundamental Research Grant Scheme (FRGS) by the Ministry of Education, Malaysia, Grant number: FP067-2018A, Geran Penyelidikan Fakulti by the Faculty of Medicine, University of Malaya, Grant number: GPF001C- 2019, and UGC mid-career award, Grant number: F.19-221/2018 (BSR) dt. 28.03.2018. We would like to request a revision to one of the funding numbers (in blue) in the funding acknowledgement below: The correct funding acknowledgement is: The study was funded by Fundamental Research Grant Scheme (FRGS) by the Ministry of Education, Malaysia, Grant number: FRGS/1/2018/STG05/UM/02/5, Geran Penyelidikan Fakulti by the Faculty of Medicine, University of Malaya, Grant number: GPF001C-2019 and UGC mid-career award, Grant number: F.19-221/2018 (BSR) dt. 28.03.2018. The original article can be found online at: https://www.eurekaselect.com/public/article/109117.