Vol 31, No 12 (2024)
- Year: 2024
- Articles: 11
- URL: https://jdigitaldiagnostics.com/0929-8673/issue/view/9998
Anti-Infectives and Infectious Diseases
Meet the Editorial Board Member



Perspectives on Iron Deficiency as a Cause of Human Disease in Global Public Health
Abstract
Iron (Fe) is a necessary trace element in numerous pathways of human metabolism. Therefore, Fe deficiency is capable of causing multiple health problems. Apart from the well-known microcytic anemia, lack of Fe can cause severe psychomotor disorders in children, pregnant women, and adults in general. Iron deficiency is a global health issue, mainly caused by dietary deficiency but aggravated by inflammatory conditions. The challenges related to this deficiency need to be addressed on national and international levels. This review aims to summarize briefly the disease burden caused by Fe deficiency in the context of global public health and aspires to offer some hands-on guidelines.



The Structure-property Relationships of Clinically Approved Protease Inhibitors
Abstract
Background:Proteases play important roles in the regulation of many physiological processes, and protease inhibitors have become one of the important drug classes. Especially because the development of protease inhibitors often starts from a substrate- based peptidomimetic strategy, many of the initial lead compounds suffer from pharmacokinetic liabilities.
Objective:To reduce drug attrition rates, drug metabolism and pharmacokinetics studies are fully integrated into modern drug discovery research, and the structure-property relationship illustrates how the modification of the chemical structure influences the pharmacokinetic and toxicological properties of drug compounds. Understanding the structure- property relationships of clinically approved protease inhibitor drugs and their analogues could provide useful information on the lead-to-candidate optimization strategies.
Methods:About 70 inhibitors against human or pathogenic viral proteases have been approved until the end of 2021. In this review, 17 inhibitors are chosen for the structure- property relationship analysis because detailed pharmacological and/or physicochemical data have been disclosed in the medicinal chemistry literature for these inhibitors and their close analogues.
Results:The compiled data are analyzed primarily focusing on the pharmacokinetic or toxicological deficiencies found in lead compounds and the structural modification strategies used to generate candidate compounds.
Conclusion:The structure-property relationships hereby summarized how the overall druglike properties could be successfully improved by modifying the structure of protease inhibitors. These specific examples are expected to serve as useful references and guidance for developing new protease inhibitor drugs in the future.



A Review on Graphene Analytical Sensors for Biomarker-based Detection of Cancer
Abstract
The engineering of nanoscale materials has broadened the scope of nanotechnology in a restricted functional system. Today, significant priority is given to immediate health diagnosis and monitoring tools for point-of-care testing and patient care. Graphene, as a one-atom carbon compound, has the potential to detect cancer biomarkers and its derivatives. The atom-wide graphene layer specialises in physicochemical characteristics, such as improved electrical and thermal conductivity, optical transparency, and increased chemical and mechanical strength, thus making it the best material for cancer biomarker detection. The outstanding mechanical, electrical, electrochemical, and optical properties of two-dimensional graphene can fulfil the scientific goal of any biosensor development, which is to develop a more compact and portable point-of-care device for quick and early cancer diagnosis. The bio-functionalisation of recognised biomarkers can be improved by oxygenated graphene layers and their composites. The significance of graphene that gleans its missing data for its high expertise to be evaluated, including the variety in surface modification and analytical reports. This review provides critical insights into graphene to inspire research that would address the current and remaining hurdles in cancer diagnosis.



Advances in the Treatment of Autism Spectrum Disorder: Current and Promising Strategies
Abstract
Autism spectrum disorder (ASD) is an umbrella term for developmental disorders characterized by social and communication impairments, language difficulties, restricted interests, and repetitive behaviors. Current management approaches for ASD aim to resolve its clinical manifestations based on the type and severity of the disability. Although some medications like risperidone show potential in regulating ASD-associated symptoms, a comprehensive treatment strategy for ASD is yet to be discovered. To date, identifying appropriate therapeutic targets and treatment strategies remains challenging due to the complex pathogenesis associated with ASD. Therefore, a comprehensive approach must be tailored to target the numerous pathogenetic pathways of ASD. From currently viable and basic treatment strategies, this review explores the entire field of advancements in ASD management up to cutting-edge modern scientific research. A novel systematic and personalized treatment approach is suggested, combining the available medications and targeting each symptom accordingly. Herein, summarize and categorize the most appropriate ways of modern ASD management into three distinct categories: current, promising, and prospective strategies.



Spinal Muscular Atrophy Treatment: The MTOR Regulatory Intervention
Abstract
Spinal muscular atrophy (SMA) is a hereditary disorder affecting neurons and muscles, resulting in muscle weakness and atrophy. Most SMA cases are diagnosed during infancy or early childhood, the most common inherited cause of infant mortality without treatment. Still, SMA might appear at older ages with milder symptoms. SMA patients demonstrate progressive muscle waste, movement problems, tremors, dysphagia, bone and joint deformations, and breathing difficulties. The mammalian target of rapamycin (mTOR), the mechanistic target of rapamycin, is a member of the phosphatidylinositol 3-kinase-related kinase family of protein kinases encoded by the mTOR gene in humans. The mTOR phosphorylation, deregulation, and autophagy have shown dissimilarity amongst SMA cell types. Therefore, exploring the underlying molecular process in SMA therapy could provide novel insights and pave the way for finding new treatment options. This paper provides new insight into the possible modulatory effect of mTOR/ autophagy in SMA management.



Single-cell Sequencing Data Reveals Aggressive CD68-type Macrophages and Prognostic Models in Bladder Cancer
Abstract
Background:The highly heterogeneous, complex pathological histology, and clinical phenotype in bladder cancer (BC) plague the prognostic management of BC to the present day.
Methods:This study was conducted using single-cell sequencing data from the gene expression omnibus (GEO) database (GSE135337). A descending, annotated analysis was performed to identify the cell types contributing to BC aggressiveness. BC cell sequencing data from The Cancer Genome Atlas (TCGA) database were then combined with univariate, least absolute shrinkage and selection operator (LASSO), multivariate COX regression analysis to identify biomarkers of BC prognosis to construct a BC. We identified biomarkers of BC prognosis to construct a prognostic risk guidance system for BC. The feedback of patients in different risk strata to immunotherapy was analyzed. Finally, the regulation of prognostic genes on cancer cell activity was verified in vitro by Western blot and cell counting kit-8 (CCK8) assays.
Results:Macrophages specifically expressing CD68 in BC were the cell type with the highest AUCell score, and CD68 was the biomarker of Tumor-associated macrophages (TAMs). CD68 macrophages were potentially the critical cell type in the aggressive BC subtype. Through univariate, LASSO, multivariate COX-based regression analysis. CTSS, GMFG, ANXA5, GSN, SLC2A3, and FTL were authenticated as prognostic biomarkers (p < 0.05) and composed the Risk Score. Patients in the low-risk group showed an excellent survival advantage (p < 0.01) and immunotherapy feedback. Additionally, inhibition of GSN expression decreased EMT activity to inhibit bladder cancer cell viability.
Conclusion:In conclusion, this study provided feedback on the immune cell types associated with aggressiveness in BC. Importantly, a prognostic management system for BC was created based on the genes involved, providing more insight into the aggressive pathological phenotype as well as the prognosis of BC.



Construction of RNA Methylation Modification-immune-related lncRNA Molecular Subtypes and Prognostic Scoring System in Lung Adenocarcinoma
Abstract
Background:RNA methylation modification is not only intimately interrelated with cancer development and progression but also actively influences immune cell infiltration in the tumor microenvironment (TME). RNA methylation modification genes influence the therapeutic progression of lung adenocarcinoma (LUAD), and mining RNA methylation modification prognosis-related markers in LUAD is crucial for its precise prognosis.
Methods:RNA-Seq data and Gene sets were collected from online databases or published literature. Genomic variation analysis was conducted by the Maftools package. RNA methylation-immune-related lncRNAs were obtained by Pearson correlation analysis. Then, Consistent clustering analysis was performed to obtain RNA methylation modification- immune molecular subtypes (RMM-I Molecular subtypes) in LUAD based on selected lncRNAs. COX and random survival forest analysis were carried out to construct the RMM-I Score. The receiver operating characteristic (ROC) curve and Kaplan Meier survival analysis were used to assess survival differences. Tumor immune microenvironment was assessed through related gene signatures and CIBERSORT algorithm. In addition, drug sensitivity analysis was executed by the pRRophetic package.
Results:Four RNA methylation modified-immune molecular subtypes (RMM-I1, RMM- I2, RMM-I3, RMM-I4) were presented in LUAD. Patients in RMM-I4 exhibited excellent survival advantages and immune activity. HAVCR2, CD274, and CTLA-4 expression were activated in RMM-I4, which might be heat tumors and a potential beneficial group for immunotherapy. OGFRP1, LINC01116, DLGAP1-AS2, CRNDE, LINC01137, MIR210HG, and CYP1B1-AS1 comprised the RMM-I Score. The RMM-I Score exhibited excellent accuracy in the prognostic assessment of LUAD, as patients with a low RMM- I Score exhibited remarkable survival advantage. Patients with a low RMM-I score might be more sensitive to treatment with Docetaxel, Vinorelbine, Paclitaxel, Cisplatin, and immunotherapy.
Conclusion:The RMM-I molecular subtype constituted the novel molecular characteristic subtype of LUAD, which complemented the existing pathological typing. More refined and accurate molecular subtypes provide help to reveal the mechanism of LUAD development. In addition, the RMM-I score offers a reliable tool for accurate prognosis of LUAD.



Heterogeneity of Lipid Metabolism and its Clinical and Immune Correlation in Lung Adenocarcinoma
Abstract
Introduction:The role of lipid metabolism in lung adenocarcinoma (LUAD) is not completely researched. Lipid metabolism reprogramming is a characteristic of malignancies and contributes to carcinogenesis and progression. The transcriptome and scRNA- seq data and clinical information were downloaded from the public databases.
Methods:Lipid metabolism pathways were collected from the MSigDB database, and molecular subtypes were classified based on lipid metabolism features via consensus clustering. The bidirectional crosstalk between immune cells and malignant cells was analyzed. Differences in lipid metabolism at the single-cell level and their correlation with the tumor microenvironment (TME) were also studied. LUAD patients were classified into two subtypes, showing distinct mutation and lipid metabolism features based on lipid metabolism characteristics. Meanwhile, significant differences in the overall survival, clinical characteristics, and immune landscape were observed between the two subtypes. We also found that clust1 had higher oxidative stress status. There were 116 differentially expressed genes between the two subtypes, which were significantly associated with cell cycle progression. We identified 4001 immune cells, including 483 malignant cells and 3518 normal cells, and found active intercellular communication and significant differences in lipid metabolism characteristics between the malignant cells and normal cells. Furthermore, several lipid metabolism pathways were found to be associated with TME factors, including hypoxia and angiogenesis.
Result:The current findings indicated that lipid metabolism was involved in the development and cellular heterogeneity of LUAD and revealed widespread reprogramming across multiple cellular elements in the TME of LUAD.
Conclusion:This characterization improved the current understanding of tumor biology and enabled the identification of novel targets for immunotherapy.



Identifying a Novel Eight-NK Cell-related Gene Signature for Ovarian Cancer Prognosis Prediction
Abstract
Background:Ovarian cancer (OVC) is the most common and costly tumor in the world with unfavorable overall survival and prognosis. This study is aimed to explore the prognostic value of natural killer cells related genes for OVC treatment.
Methods:RNA-seq and clinical information were acquired from the TCGA-OVC dataset (training dataset) and the GSE51800 dataset (validation dataset). Genes linked to NK cells were obtained from the immPort dataset. Moreover, ConsensusClusterPlus facilitated the screening of molecular subtypes. Following this, the risk model was established by LASSO analysis, and immune infiltration and immunotherapy were then detected by CIBERSORT, ssGSEA, ESTIMATE, and TIDE algorithms.
Results:Based on 23 NK cell-related genes with prognosis, TCGA-OVC samples were classified into two clusters, namely C1 and C2. Of these, C1 had better survival outcomes as well as enhanced immune infiltration and tumor stem cells. Additionally, it was more suitable for immunotherapy and was also sensitive to traditional chemotherapy drugs. The eight-gene prognosis model was constructed and verified via the GSE51800 dataset. Additionally, a high infiltration level of immune cells was observed in low-risk patients. Low-risk samples also benefited from immunotherapy and chemotherapy drugs. Finally, a nomogram and ROC curves were applied to validate model accuracy.
Conclusion:The present study identified a RiskScore signature, which could stratify patients with different infiltration levels, immunotherapy, and chemotherapy drugs. Our study provided a basis for precisely evaluating OVC therapy and prognosis.



Identification of Key Genes in Angiogenesis of Breast and Prostate Cancers in the Context of Different Cell Types
Abstract
Introduction:Angiogenesis involves the development of new blood vessels. Biochemical signals start this process in the body, which is followed by migration, growth, and differentiation of endothelial cells that line the inside wall of blood vessels. This process is vital for the growth of cancer cells and tumors.
Materials and Methods:We started our analysis by composing a list of genes that have a validated impact in humans with respect to angiogenesis-related phenotypes. Here, we have investigated the expression patterns of angiogenesis-related genes in the context of previously published single-cell RNA-Seq data from prostate and breast cancer samples.
Results:Using a protein-protein interaction network, we showed how different modules of angiogenesis-related genes are overexpressed in different cell types. In our results, genes, such as ACKR1, AQP1, and EGR1, showed a strong cell type-dependent overexpression pattern in the two investigated cancer types, which can potentially be helpful in the diagnosis and follow-up of patients with prostate and breast cancer.
Conclusion:Our work demonstrates how different biological processes in distinct cell types contribute to the angiogenesis process, which can provide clues regarding the potential application of targeted inhibition of the angiogenesis process.


