Vol 31, No 13 (2024)
- Year: 2024
- Articles: 11
- URL: https://rjmseer.com/0929-8673/issue/view/10002
Anti-Infectives and Infectious Diseases
Meet the Editorial Board Member



Beyond the Dusty Fog: Local Eye Drop Therapy and Potentially New Treatment Alternatives in Pseudoexfoliative Glaucoma
Abstract
Pseudoexfoliative glaucoma (PEG) is a type of secondary open-angle glaucoma characterized by the accumulation of whitish-gray material on the trabecular meshwork and lens, leading to an increase in intraocular pressure (IOP) and optic nerve damage. Local eye drop therapy is one of the first-line treatments for PEG, which include prostaglandin analogues, beta-blockers, and alpha-adrenergic agonists to lower IOP. New treatments beyond conventional techniques, however, are constantly being developed. One potential treatment proposed for PEG is based on magnetic phage display, which involves using magnetic nanoparticles conjugated to specific peptides or proteins selected using phage display techniques to remove aggregates in the anterior chamber of the eye or inflammatory cells and cytokines that contribute to PEG pathogenesis. Other potential treatments include microRNAs (miRNAs) that are involved in the regulation of gene expression at the post-transcription stages. Gene therapies, nanotechnology, immunotherapy and methods based on stem cells can also be potentially used to target and treat specific tissues and cells responsible for regulating IOP. In addition, photobiomodulation therapy (PBMT), a non-invasive procedure that utilizes low-level laser therapy to improve cellular function and promote tissue repair, can prove an interesting alternative in treating PEG. The aim of our mini-review is to provide a brief overview of these innovative methods that appear to offer potentially promising treatment options for PEG.



Early-Life Lead Exposure: Risks and Neurotoxic Consequences
Abstract
Background:Lead (Pb) does not have any biological function in a human, and it is likely no safe level of Pb in the human body. The Pb exposure impacts are a global concern for their potential neurotoxic consequences. Despite decreasing both the environmental Pb levels and the average blood Pb levels in the survey populations, the lifetime redistribution from the tissues-stored Pb still poses neurotoxic risks from the low-level exposure in later life. The growing fetus and children hold their innate high-susceptible to these Pb-induced neurodevelopmental and neurobehavioral effects.
Objective:This article aims to evaluate cumulative studies and insights on the topic of Pb neurotoxicology while assessing the emerging trends in the field.
Results:The Pb-induced neurochemical and neuro-immunological mechanisms are likely responsible for the high-level Pb exposure with the neurodevelopmental and neurobehavioral impacts at the initial stages. Early-life Pb exposure can still produce neurodegenerative consequences in later life due to the altered epigenetic imprints and the ongoing endogenous Pb exposure. Several mechanisms contribute to the Pb-induced neurotoxic impacts, including the direct neurochemical effects, the induction of oxidative stress and inflammation through immunologic activations, and epigenetic alterations. Furthermore, the individual nutritional status, such as macro-, micro-, or antioxidant nutrients, can significantly influence the neurotoxic impacts even at low-level exposure to Pb.
Conclusion:The prevention of early-life Pb exposure is, therefore, the critical determinant for alleviating various Pb-induced neurotoxic impacts across the different age groups.



CD155-TIGIT Axis as a Therapeutic Target for Cancer Immunotherapy
Abstract
Immune checkpoint inhibitors (ICIs) have shown unprecedented efficacy in treating many advanced cancers. Although FDA-approved ICIs have shown promising efficacy in treating many advanced cancers, their application is greatly limited by the low response rate, immune-related adverse events (irAE), and drug resistance. Developing novel ICIs holds great promise to improve the survival and prognosis of advanced cancer patients. T-Cell immunoglobulin and ITIM domain (TIGIT) is an inhibitory receptor expressed on T cells, natural killer (NK) cells, and T regulatory cells. Increasing reports have shown that the disrupting CD155-TIGIT axis could activate the immune system and restore antitumor immune response. This review briefly summarized the role of TIGIT in tumor immune escape and targeting CD155-TIGIT axis drugs in preclinical and clinical trials for cancer immunotherapy.



Advances in Genetic Reprogramming: Prospects from Developmental Biology to Regenerative Medicine
Abstract
The foundations of cell reprogramming were laid by Yamanaka and co-workers, who showed that somatic cells can be reprogrammed into pluripotent cells (induced pluripotency). Since this discovery, the field of regenerative medicine has seen advancements. For example, because they can differentiate into multiple cell types, pluripotent stem cells are considered vital components in regenerative medicine aimed at the functional restoration of damaged tissue. Despite years of research, both replacement and restoration of failed organs/ tissues have remained elusive scientific feats. However, with the inception of cell engineering and nuclear reprogramming, useful solutions have been identified to counter the need for compatible and sustainable organs. By combining the science underlying genetic engineering and nuclear reprogramming with regenerative medicine, scientists have engineered cells to make gene and stem cell therapies applicable and effective. These approaches have enabled the targeting of various pathways to reprogramme cells, i.e., make them behave in beneficial ways in a patient-specific manner. Technological advancements have clearly supported the concept and realization of regenerative medicine. Genetic engineering is used for tissue engineering and nuclear reprogramming and has led to advances in regenerative medicine. Targeted therapies and replacement of traumatized , damaged, or aged organs can be realized through genetic engineering. Furthermore, the success of these therapies has been validated through thousands of clinical trials. Scientists are currently evaluating induced tissue-specific stem cells (iTSCs), which may lead to tumour-free applications of pluripotency induction. In this review, we present state-of-the-art genetic engineering that has been used in regenerative medicine. We also focus on ways that genetic engineering and nuclear reprogramming have transformed regenerative medicine and have become unique therapeutic niches.



Multiple Natural Polymers in Drug and Gene Delivery Systems
Abstract
Background:Natural polymers are organic compounds produced by living organisms. In nature, they exist in three main forms, including proteins, polysaccharides, and nucleic acids. In recent years, with the continuous research on drug and gene delivery systems, scholars have found that natural polymers have promising applications in drug and gene delivery systems due to their excellent properties such as biocompatibility, biodegradability, low immunogenicity, and easy modification. However, since the structure, physicochemical properties, pharmacological properties and biological characteristics of biopolymer molecules have not yet been entirely understood, further studies are required before large-scale clinical application. This review focuses on recent advances in the representative natural polymers such as proteins (albumin, collagen, elastin), polysaccharides (chitosan, alginate, cellulose) and nucleic acids. We introduce the characteristics of various types of natural polymers, and further outline the characterization methods and delivery forms of these natural polymers. Finally, we discuss possible challenges for natural polymers in subsequent experimental studies and clinical applications. It provides an important strategy for the clinical application of natural polymers in drug and gene delivery systems.



Role of LncRNA MIAT in Diabetic Complications
Abstract
Long non-coding RNA (LncRNA) refers to a large class of RNAs with over 200 nucleotides that do not have the function of encoding proteins. In recent years, more and more literature has revealed that lncRNA is involved in manipulating genes related to human health and disease, playing outstanding biological functions, which has attracted widespread attention from researchers. The newly discovered long-stranded non-coding RNA myocardial infarction-related transcript (LncRNA MIAT) is abnormally expressed in a variety of diseases, especially in diabetic complications, and has been proven to have a wide range of effects. This review article aimed to summarize the importance of LncRNA MIAT in diabetic complications, such as diabetic cardiomyopathy, diabetic nephropathy, and diabetic retinopathy, and highlight the latest findings on the pathway and mechanism of its participation in regulating diabetic complications, which may aid in finding new intervention targets for the treatment of diabetic complications. LncRNA MIAT competitively binds microRNAs to regulate gene expression as competitive endogenous RNAs. Thus, this review article has reviewed the biological function and pathogenesis of LncRNA MIAT in diabetic complications and described its role in diabetic complications. This paper will help in finding new therapeutic targets and intervention strategies for diabetes complications.



The Effect of Statin Therapy on Serum Uric Acid Levels: A Systematic Review and Meta-analysis
Abstract
Background:Elevated concentrations of serum uric acid (SUA) are associated with several conditions, including cardiovascular disease. The present study aimed to estimate the impact of statin therapy on SUA levels through a systematic review and meta-analysis of clinical trials.
Methods:PubMed, Embase, Web of Science, and Scopus were searched on January 14, 2022, to identify eligible clinical trials. The intervention group received statins as monotherapy or in combination with other drugs, and the control group received non-statins or placebo. Studies reporting SUA levels before and after treatment were selected for further analysis. Finally, the data were pooled, and the mean changes in SUA, total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides were reported.
Results:Out of 1269 identified studies, 23 were included in the review. A total of 3928 participants received statin therapy, and 1294 were included in control groups. We found a significant reduction in SUA levels following statin therapy (mean difference (MD) = -26.67 µmol/L with 95% confidence interval (CI) [-44.75, -8.60] (P =0.004)). Atorvastatin (MD = -37.93 µmol/L [-67.71, -8.15]; p < 0.0001), pravastatin (MD = -12.64 µmol/L [-18.64, -6.65]; p < 0.0001), and simvastatin (MD = -5.95 µmol/L [-6.14, -5.80]; p < 0.0001), but not rosuvastatin, were significantly associated with a reduction in SUA levels. An analysis comparing different types of statins showed that pravastatin 20-40 mg/day could significantly reduce SUA when compared to simvastatin 10-20 mg/day (-21.86 µmol/L [-36.33,-7.39]; P =0.003).
Conclusion:Statins were significantly associated with a decrease in SUA levels, particularly atorvastatin, which was found to be most effective in lowering SUA. Atorvastatin may be the most appropriate cholesterol-lowering agent for patients with or at risk of hyperuricemia.



Inflammatory Response Modulation by Low-Dose Anti-inflammatory Drugs Treatment in an In Vitro Osteoarthritis Cellular Model
Abstract
Background:Low-dose-medicine is based on the administration of low doses of biological regulators to restore the immunologic balance altered in the disease. Cytokines are pivotal regulators of cellular and tissue functions and impaired crosstalk, due to an imbalance between specific cytokines, it is fundamental in acute inflammation and diseases correlated to low-grade chronic inflammation. Osteoarthritis is the most prevalent arthritic disease and a leading cause of disability. In the treatment of muscle- skeletal pathologies, the therapeutic integration of conventional medicine with homotoxicology, or low-dose-medicine appears to be beneficial.
Objective:This study aims to get more insights into the role of inflammatory cytokines and chemokines during the development of osteoarthritis and to evaluate a possible blocking strategy using anti-inflammatory molecules, we resort to an in vitro experimental model using an established human chondrosarcoma cell line that underwent to a well known pro-inflammatory stimulus as bacterial lipopolysaccharide.
Methods:We tested the production of inflammatory-related cytokines and chemokines, and the efficacy of low-dose (LD) administration of anti-inflammatory compounds, namely IL-10 and anti-IL-1, to block inflammatory cellular pathways.
Results:Following an inflammatory insult, chondrocytes upregulated the expression of several pro-inflammatory cyto-/chemokines and this induction could be counteracted by LD IL-10 and anti-IL-1. We reported that these effects could be ascribed to an interfering effect of LD drugs with the NF-κB signaling.
Conclusion:Our results provided a good indication that LD drugs can be effective in inhibiting the inflammatory response in chondrocytes opening the way to new therapies for the treatment of diseases such as osteoarthritis.



Identification of a Novel Diagnosis Model based on 5 Hub Genes for Chronic Thromboembolic Pulmonary Hypertension
Abstract
Background:As a type of precapillary pulmonary hypertension, chronic thromboembolic pulmonary hypertension (CTEPH) results from incomplete pulmonary embolism resolution. In this study, we aimed to determine biomarker genes for predicting the prognosis of CTEPH.
Methods:RNAseq of CTEPH was collected from the public database, namely Gene Expression Omnibus (GEO), including GSE84538 and GSE188938, which combined a dataset (GSE). Differentially expressed genes (DEG) or miRNA (DEM) were identified by limma package. Functional enrichment analysis was performed by the WebGestaltR package. Then, the miRNA-mRNA network was presented by Cytoscape, and the protein-protein interactions (PPI) network was constructed by STRING. MCODE was mined by mature MCODE algorithm. Immune infiltration analysis was conducted by ESTIMATER and ssGSEA analysis. A diagnosis model was established by SVM algorithm.
Results:In the GSE dataset, CTEPH samples had a lower GOBP_RESPONSE_- TO_OXIDATIVE_STRESS score. A total of 628 DEGs and 31 DEMs were identified between CTEPH and normal samples. Afterward, DEGs were intersected with genes, which correlated with the GOBP_RESPONSE_TO_OXIDATIVE_STRESS score. A 26 DEMs-152 DEGs network was constructed, and a PPI network was established based on 152 DEGs to find 149 target genes. From the above 149 target genes, 3 modules were extracted to obtain 15 core targets. Finally, 5 hub genes were obtained by the intersection of 15 core targets and genes in MCODE2. A total of 5 hub genes were positively correlated with most immune cell scores as well as GOBP_RESPONSE_TO_OXIDATIVE_ STRESS. It was found that a diagnosis model based on 5 hub genes had a well diagnostic ability for CTEPH.
Conclusion:We identified 5 hub genes associated with oxidative stress. It can be concluded that they may be beneficial in diagnosing CTEPH.



Metabolome Profiling of Malignant Ascites Identifies Candidate Metabolic Biomarkers of Hepatocellular Carcinoma
Abstract
Background:Malignant ascites is one of the severe complications of hepatocellular carcinoma, which can be regarded as a unique tumor microenvironment of hepatocellular carcinoma. The identification of novel biomarkers in malignant ascites could be crucial to differentiate patients with hepatocellular carcinoma and cirrhotic ascites.
Objective:The study aimed to distinguish the metabolomics of malignant ascites in patients with hepatocellular carcinoma from that of non-malignant ascites (cirrhotic ascites).
Methods:Liquid chromatography-mass spectrometry was performed to analyze the differentially distributed biomarkers in patients with malignant ascites and hepatocellular carcinoma (n = 39), as well as in patients with cirrhotic ascites, which were taken as controls (n = 36).
Results:Our results suggest that the key factors associated with pathways, such as arachidonic acid, phenylalanine, and glutamic acid pathways, are potential ascitic fluidbased biomarkers for differentiating hepatocellular carcinoma with cirrhosis ascites; the results also provide a clinical pathophysiological interpretation of biomarkers and metabolic pathways relevant to disease status.
Conclusion:Our results suggest that the key factors associated with pathways, such as arachidonic acid, phenylalanine, and glutamic acid pathways, are potential ascitic fluidbased biomarkers for differentiating hepatocellular carcinoma with cirrhosis ascites; the results also provide a clinical pathophysiological interpretation of biomarkers and metabolic pathways relevant to disease status.


