The proto-oncogene c-Fos is known as a reliable marker of cell activation, which is immediately induced after a new stimulus in specific brain regions, depending on the nature of the stimulus applied. However, the expression of c-Fos is increased in Alzheimer’s disease (AD) and contributes to amyloid β-peptide-induced neurotoxicity. This review attempted to focus on the role of c-Fos in learning and memory in both healthy brain and AD, emphasizing on possible mechanisms. Comparing the available findings, regarding learning and memory, c-Fos expression leads to memory formation through ERK (extracellular signal-regulated kinase)/CREB (cAMP response element-binding protein) and long-term potentiation, while it is down regulated after the repetition and habituation of stimuli. However, its overexpression in neurons and glia of AD, contributes to cognitive deficits and neuronal loss, which represents a defect in its ability to habituate to repeated stimuli. Also, expression pattern in glial is associated with constitutive CREB activation following increasing amyloid beta (Aβ), activation transcription factor (ATF3), and cytochrome c in apoptosis pathways. Thus, two contradictory roles of c-Fos in the healthy brain and AD, reveal more complexity in c-Fos up and down stream signaling pathways, bioavailability, and sensitivity. Future studies focusing on c-Fos modulation, might offer promising strategies to mitigate cognitive decline in AD.

Tumors are complex systems characterized by variations across genetic, transcriptomic, phenotypic, and microenvironmental levels. This study introduced a novel framework for quantifying cancer cell heterogeneity using single-cell RNA sequencing data. The framework comprised several scores aimed at uncovering the complexities of key cancer traits, such as metastasis, tumor progression, and recurrence.

This study leveraged publicly available single-cell transcriptomic data from three human breast cancer subtypes: estrogen receptor-positive, human epidermal growth factor receptor 2-positive, and triple-negative. We employed a quantitative approach, analyzing copy number alterations (CNAs), entropy, transcriptomic heterogeneity, and diverse protein-protein interaction networks (PPINs) to explore critical concepts in cancer biology.

We found that entropy and PPIN activity related to the cell cycle could distinguish cell clusters with elevated mitotic activity, particularly in aggressive breast cancer subtypes. Additionally, CNA distributions varied across cancer subtypes. We also identified positive correlations between the CNA score, entropy, and the activities of PPINs associated with the cell cycle, as well as those linked to basal and mesenchymal cell lines.

This study addresses a gap in the current understanding of breast cancer heterogeneity by presenting a novel quantitative approach that offers deeper insights into tumor biology, surpassing traditional marker-based methods.

Cardiovascular diseases (CVDs) remain the leading cause of global morbidity and mortality, highlighting the urgent need for innovative diagnostic and prognostic approaches to address their complex pathophysiology. Recent advances in molecular cardiology have unveiled immune-derived microRNAs (miRNAs), or immuno-miRs, as pivotal regulators in the interplay between immune responses and cardiovascular pathology. Secreted by immune cells such as T lymphocytes, macrophages, and neutrophils, these small non-coding RNAs modulate critical signaling pathways by regulating gene expression. Immuno-miRs influence essential processes, including inflammation, endothelial dysfunction, and fibrotic remodeling—core mechanisms underlying conditions such as atherosclerosis, myocardial infarction, and heart failure. Moreover, their presence in systemic circulation within extracellular vesicles underscores their role in intercellular communication, impacting both immune and non-immune cardiovascular cells, such as cardiomyocytes and endothelial cells. This dual functionality renders immuno-miRs promising candidates as diagnostic biomarkers for early disease detection and as prognostic tools for assessing disease progression and therapeutic efficacy. Furthermore, emerging miRNA-based interventions—such as miRNA mimics and inhibitors—show considerable promise in modulating immune dysregulation in CVDs, although clinical translation remains a significant challenge. In this review, we comprehensively examine the regulatory roles of immuno-miRs in both innate and adaptive immune responses and explore recent advancements in miRNA-based therapies. By consolidating current knowledge and identifying existing gaps, we provide a comprehensive overview of the transformative potential of immuno-miRs in CVD management. Integrating these molecules into personalized medicine may pave the way for more effective, targeted, and minimally invasive strategies to combat one of the world’s most pressing health challenges.

With the improvement of living standards in recent years, up to 90% of obese patients have nonalcoholic fatty liver disease (NAFLD). The number of nonalcoholic steatohepatitis (NASH)-related deaths will gradually increase, and NASH is expected to be the most common cause of liver-related deaths in the future. Therefore, there is an urgent need to find effective and reliable serum biomarkers to distinguish simple hepatic steatosis (SS) from NASH. Liver cell regeneration, oxidative stress-induced DNA methylation, and biliary epithelial cell proliferation were reported to increase serum alpha-fetoprotein (AFP) levels. AFP has long been used as a tool to monitor liver cancer. However, the function of AFP in NAFLD, especially NASH, has not been clarified. Moreover, whether an elevated AFP level indicates the occurrence of NASH or serves as a serum biomarker remains to be elucidated. The miRNA-122 pathway, DNA methylation and DNA damage, and activation of resident stem cells and/or progenitor cells in the liver, as well as necrosis, regeneration, and repair of liver cells, may contribute to slight increases in AFP levels in the development of NASH in patients with NAFLD. Furthermore, mildly elevated AFP levels may indicate the development of NASH. This review explores the role of elevated AFP levels in the development of NASH, with a specific focus on the underlying molecular mechanisms and the clinical significance.

Nonalcoholic fatty liver disease (NAFLD) has become one of the most common and important chronic liver diseases worldwide. Some chronic infectious diseases are associated with the risk of NAFLD. These can induce abnormal glucose and lipid metabolism, insulin resistance, inflammatory activation and other responses, which increase the risk of progression of liver fibrosis. The present study describes the pathogenesis and management of NAFLD with chronic infectious diseases, such as hepatitis B virus, hepatitis C virus, Helicobacter pylori, and human immunodeficiency virus infections.

Diabetes mellitus (DM) is an established risk for biliary tract cancer (BTC). Metformin, an anti-diabetes medication, has been reported for its association with a reduced risk of BTC. However, the controversy about metformin’s benefit among epidemiological studies is unresolved. This study is to investigate metformin’s effects on the development and progression of BTC.

Literature searches were performed, without language restriction, in Pubmed, Embase, and Web of Science, from their respective inceptions to February 28, 2023. All studies were screened by two researchers using Covidence. Quality assessment was performed using the Newcastle-Ottawa Scale. Meta-analyses were performed by a fixed and random-effect model using RevMan version 5.4.

Nine observational studies met the inclusion criteria and were included in the meta-analysis. With pooled samples of 24,743,526 individuals from 4 case-control and 2 cohort studies, metformin was not associated with a decreased risk of BTC (pooled RR: 0.82, 95% CI: 0.42–1.59, p = 0.56). Sub-group analyses in each study design also revealed a null effect of metformin. Meta-analysis of 3 cohort studies reporting the association between metformin and survival of patients with BTC with a pooled sample of 1,163 patients showed a marginally significant effect of metformin on survival outcome improvement in both fixed effect models (pooled RR: 0.83, 95% CI: 0.68–1.00, p = 0.05), and random-effect model (pooled RR: 0.83, 95% CI: 0.68–1.01, p = 0.07).

Meta-analyses of available observational studies show that metformin was neither significantly associated with decreased risk nor, survival improvement for BTC patients who had DM.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in developed countries, contributing to ∼24% of cases worldwide and includes non-alcoholic steatohepatitis. High-throughput OMICS approaches have been used to characterize NAFLD conditions for the identification of potential molecular signatures or differentially regulated molecules (DEMs). The present study aims to perform a systematic review and meta-analysis from an omics perspective.

We analyzed the publically available data set (accession number: GSE63067) from the Gene Expression Omnibus (GEO) using the GEO2R program. The differentially expressed genes (DEGs) were filtered using the criteria where genes with p-value ≤0.05 and fold-change ≥2.0-fold (upregulated), and fold-change ≤0.5-fold (downregulated).

We identified 264 differentially expressed genes (DEGs) between NAFLD and normal liver tissue samples, where 211 were upregulated and 53 were downregulated in NAFLD. Additionally, we identified novel genes sphingomyelin synthase 2 and WNK lysine deficient protein kinase 3 that were not well understood in the molecular pathophysiology of NAFLD. Further gene ontology-based analysis revealed that among biological processes, cellular components, and molecular functions were also dysregulated in NAFLD.

Our study shows that meta-analysis of publicly available data is useful for the identification of DEGs and indication of dysregulated biological processes in NAFLD, which provide valuable insights into the molecular mechanisms of NAFLD.

Rapidly proliferating cancer cells exhibit a high energy demand. However, their utilization of the glycolytic pathway is inefficient, leading to a compensatory effect wherein cancer cells consume ten to twenty times more glucose than normal cells. In cases where glucose availability is limited due to a poorly perfused hypoxic microenvironment, cancer cells resort to alternative energy sources, including fructose. Certain tumors have been found to rely heavily on fructose, and fructose utilization contributes to pro-tumoral signaling and increased cancer risk. Over the past 70 years, dietary fructose intake has steadily increased, resulting in a rise in obesity and metabolic syndrome, both of which elevate cancer risk. In this paper, we present compelling evidence that highlights the role of fructose and the glucose transporter GLUT5 in promoting specific types of tumors. We summarize the existing evidence and pathways through which fructose contributes to cancer metabolism, particularly in cases where glucose availability is restricted. Furthermore, we propose a hypothesis that elucidates the regulation of the lipogenic phenotype by dietary fructose intake and cellular energy status. It is important to note that the effects of fructose are context-dependent, with its tumor-promoting effects varying based on the energy status of the cell. We comprehensively analyze why targeting fructose uptake and fructolysis should be important for the management of some tumors and cancer prevention.

With the improvement of living standards in recent years, up to 90% of obese patients have nonalcoholic fatty liver disease (NAFLD). The number of nonalcoholic steatohepatitis (NASH)-related deaths will gradually increase, and NASH is expected to be the most common cause of liver-related deaths in the future. Therefore, there is an urgent need to find effective and reliable serum biomarkers to distinguish simple hepatic steatosis (SS) from NASH. Liver cell regeneration, oxidative stress-induced DNA methylation, and biliary epithelial cell proliferation were reported to increase serum alpha-fetoprotein (AFP) levels. AFP has long been used as a tool to monitor liver cancer. However, the function of AFP in NAFLD, especially NASH, has not been clarified. Moreover, whether an elevated AFP level indicates the occurrence of NASH or serves as a serum biomarker remains to be elucidated. The miRNA-122 pathway, DNA methylation and DNA damage, and activation of resident stem cells and/or progenitor cells in the liver, as well as necrosis, regeneration, and repair of liver cells, may contribute to slight increases in AFP levels in the development of NASH in patients with NAFLD. Furthermore, mildly elevated AFP levels may indicate the development of NASH. This review explores the role of elevated AFP levels in the development of NASH, with a specific focus on the underlying molecular mechanisms and the clinical significance.