Examining the clinical relevance of metformin as an antioxidant intervention

In physiological concentrations, reactive oxygen species play a vital role in regulating cell signaling and gene expression. Nevertheless, oxidative stress is implicated in the pathogenesis of numerous diseases and can inflict damage on diverse cell types and tissues. Thus, understanding the factors that mitigate the deleterious effects of oxidative stress is imperative for identifying new therapeutic targets. In light of the absence of direct treatment recommendations for reducing oxidative stress, there is a continuing need for fundamental research that utilizes innovative therapeutic approaches. Metformin, known for its multifaceted beneficial properties, is acknowledged for its ability to counteract the adverse effects of increased oxidative stress at both molecular and cellular levels. In this review, we delve into recent insights regarding metformin’s antioxidant attributes, aiming to expand its clinical applicability. Our review proposes that metformin holds promise as a potential adjunctive therapy for various diseases, given its modulation of oxidative stress characteristics and regulation of diverse metabolic pathways. These pathways include lipid metabolism, hormone synthesis, and immunological responses, all of which may experience dysregulation in disease states, contributing to increased oxidative stress. Furthermore, our review introduces potential novel metformin-based interventions that may merit consideration in future research. Nevertheless, the necessity for clinical trials involving this drug remains imperative, as they are essential for establishing therapeutic dosages and addressing challenges associated with dose-dependent effects

Future Perspectives in Oxidative Stress in Trisomy 13 and 18 Evaluation

Autosomal aneuploidies are the most frequently occurring congenital abnormalities and are related to many metabolic disorders, hormonal dysfunctions, neurotransmitter abnormalities, and intellectual disabilities. Trisomies are generated by an error of chromosomal segregation during cell division. Accumulating evidence has shown that deregulated gene expression resulting from the triplication of chromosomes 13 and 18 is associated with many disturbed cellular processes. Moreover, a disturbed oxidative stress status may be implicated in the occurrence of fetal malformations. Therefore, a literature review was undertaken to provide novel insights into the evaluation of trisomy 13 (T13) and 18 (T18) pathogeneses, with a particular concern on the oxidative stress. Corresponding to the limited literature data focused on factors leading to T13 and T18 phenotype occurrence, the importance of oxidative stress evaluation in T13 and T18 could enable the determination of subsequent disturbed metabolic pathways, highlighting the related role of mitochondrial dysfunction or epigenetics. This review illustrates up-to-date T13 and T18 research and discusses the strengths, limitations, and possible directions for future studies. The progressive unification of trisomy-related research protocols might provide potential medical targets in the future along with the implementation of the foundation of modern prenatal medicine

Future Perspectives in Oxidative Stress in Trisomy 13 and 18 Evaluation

Autosomal aneuploidies are the most frequently occurring congenital abnormalities and are related to many metabolic disorders, hormonal dysfunctions, neurotransmitter abnormalities, and intellectual disabilities. Trisomies are generated by an error of chromosomal segregation during cell division. Accumulating evidence has shown that deregulated gene expression resulting from the triplication of chromosomes 13 and 18 is associated with many disturbed cellular processes. Moreover, a disturbed oxidative stress status may be implicated in the occurrence of fetal malformations. Therefore, a literature review was undertaken to provide novel insights into the evaluation of trisomy 13 (T13) and 18 (T18) pathogeneses, with a particular concern on the oxidative stress. Corresponding to the limited literature data focused on factors leading to T13 and T18 phenotype occurrence, the importance of oxidative stress evaluation in T13 and T18 could enable the determination of subsequent disturbed metabolic pathways, highlighting the related role of mitochondrial dysfunction or epigenetics. This review illustrates up-to-date T13 and T18 research and discusses the strengths, limitations, and possible directions for future studies. The progressive unification of trisomy-related research protocols might provide potential medical targets in the future along with the implementation of the foundation of modern prenatal medicine

Metformin Intervention—A Panacea for Cancer Treatment?

The molecular mechanism of action and the individual influence of various metabolic pathways related to metformin intervention are under current investigation. The available data suggest that metformin provides many advantages, exhibiting anti-inflammatory, anti-cancer, hepatoprotective, cardioprotective, otoprotective, radioprotective, and radio-sensitizing properties depending on cellular context. This literature review was undertaken to provide novel evidence concerning metformin intervention, with a particular emphasis on cancer treatment and prevention. Undoubtedly, the pleiotropic actions associated with metformin include inhibiting inflammatory processes, increasing antioxidant capacity, and improving glycemic and lipid metabolism. Consequently, these characteristics make metformin an attractive medicament to translate to human trials, the promising results of which were also summarized in this review

Identification of MicroRNA Profiles in Fetal Spina Bifida: The Role in Pathomechanism and Diagnostic Significance

Distinct miRNA expression patterns may reflect anomalies related to fetal congenital malformations such as spinal bifida (SB). The aim of this preliminary study was to determine the maternal miRNA expression profile of women carrying fetuses with SB. Therefore, six women carrying fetuses with SB and twenty women with euploid healthy fetuses were enrolled in this study. Using NanoString technology, we evaluated the expression level of 798 miRNAs in both plasma and amniotic fluid samples. A downregulation of miR-1253, miR-1290, miR-194-5p, miR-302d-3p, miR-3144-3p, miR-4536-5p, miR-548aa + miR-548t-3p, miR-548ar-5p, miR-548n, miR-590-5p, miR-612, miR-627-5p, miR-644a, and miR-122-5p, and an upregulation of miR-320e, let-7b-5p, miR-23a-3p, miR-873-3p, and miR-30d-5p were identified in maternal amniotic fluid samples in SB when compared to the control group. The target genes of these miRNAs play a predominant role in regulating the synthesis of several biological compounds related to signaling pathways such as those regulating the pluripotency of stem cells. Moreover, the maternal plasma expression of miR-320e was increased in pregnancies with SB, and this marker could serve as a valuable non-invasive screening tool. Our results highlight the SB-specific miRNA signature and the differentially expressed miRNAs that may be involved in SB pathogenesis. Our findings emphasize the role of miRNA as a predictive factor that could potentially be useful in prenatal genetic screening for SB

Liver injury in patients with COVID-19 without underlying liver disease

SARS-CoV-2 shows a high affinity for the ACE-2 receptor, present on the epithelial cells of the upper and lower respiratory tract, within the intestine, kidneys, heart, testes, biliary epithelium, and—where it is particularly challenging—on vascular endothelial cells. Liver involvement is a rare manifestation of COVID-19. Material and Methods: We reviewed 450 patients admitted due to the fact of SARS-CoV-2 infection (COVID-19) including 88 with liver injury. Based on medical history and previous laboratory test results, we excluded cases of underlying liver disease. The analysis involved a clinical course of COVID-19 in patients without underlying liver disease as well as the type and course of liver injury. Results: Signs and symptoms of liver injury were present in 20% of patients, mostly presenting as a mixed-type pattern of injury with less common cases of standalone hepatocellular (parenchymal) or cholestatic injury. The liver injury symptoms resolved at the end of inpatient treatment in 20% of cases. Sixteen patients died with no cases where liver injury would be deemed a cause of death. Conclusions: (1) Liver injury secondary to COVID-19 was mild, and in in 20%, the signs and symptoms of liver injury resolved by the end of hospitalization. (2) It seems that liver injury in patients with COVID-19 was not associated with a higher risk of mortality. (3) The underlying mechanism of liver injury as well as its sequelae are not fully known. Therefore, caution and further monitoring are advised, especially in patients whose liver function tests have not returned to normal values

The Relationship between Oxidative Status and Radioiodine Treatment Qualification among Papillary Thyroid Cancer Patients

Total oxidative status (TOS), total antioxidant capacity (TAC), tumor protein 53 (p53), nuclear factor kappa B (NF-κB), forkhead box protein O1 (FOXO), and sirtuin 1 (SIRT1) play crucial roles in oxidative homeostasis and the progression of papillary thyroid cancer (PTC), as previously demonstrated in the literature. Therefore, profiling these markers among PTC patients may be useful in determining their eligibility for radioiodine (RAI) treatment. Since treatment indications are based on multiple and dynamic recommendations, additional criteria for adjuvant RAI therapy are still needed. In our study, we evaluated the TOS, TAC, and serum concentrations of p53, NF-κB, FOXO, and SIRT1 to analyze the relationship between oxidative status and qualification for RAI treatment. For the purpose of this study, we enrolled 60 patients with PTC allocated for RAI treatment as the study group and 25 very low-risk PTC patients not allocated for RAI treatment as a reference group. The serum TOS and SIRT1 concentrations were significantly higher in the study group compared to the reference group (both p p < 0.05). We also demonstrated the diagnostic utility of TAC (AUC = 0.987), FOXO (AUC = 0.648), TOS (AUC = 0.664), SIRT1 (AUC = 0.709), p53 (AUC = 0.664), and NF-κB (AUC = 0.651) measurements as indications for RAI treatment based on American Thyroid Association recommendations. Our study revealed that oxidative status-related markers may become additional criteria for RAI treatment in PTC patients

Expression Profile and Diagnostic Significance of MicroRNAs in Papillary Thyroid Cancer

The incidence of papillary thyroid cancer (PTC) has increased in recent years. To improve the diagnostic management of PTC, we propose the use of microRNAs (miRNAs) as a biomarker. Our aim in this study was to evaluate the miRNA expression pattern in PTC using NanoString technology. We identified ten miRNAs deregulated in PTC compared with reference tissue: miR-146b-5p, miR-221-3p, miR-221-5p, miR-34-5p, miR-551b-3p, miR-152-3p, miR-15a-5p, miR-31-5p, and miR-7-5p (FDR < 0.05; |fold change (FC)| ≥ 1.5). The gene ontology (GO) analysis of differentially expressed miRNA (DEM) target genes identified the predominant involvement of epidermal growth factor receptor (EGFR), tyrosine kinase inhibitor resistance, and pathways in cancer in PTC. The highest area under the receiver operating characteristic (ROC) curve (AUC) for DEMs was found for miR-146-5p (AUC = 0.770) expression, indicating possible clinical applicability in PTC diagnosis. The combination of four miRNAs (miR-152-3p, miR-221-3p, miR-551b-3p, and miR-7-5p) showed an AUC of 0.841. Validation by real-time quantitative polymerase chain reactions (qRT-PCRs) confirmed our findings. The introduction of an miRNA diagnostic panel based on the results of our study may help to improve therapeutic decision making for questionable cases. The use of miRNAs as biomarkers of PTC may become an aspect of personalized medicine