Terahertz (THz) radiation is increasingly explored for biomedical applications, however, its non-thermal effects on cellular metabolism and regulatory networks remain insufficiently characterized. This study aimed to investigate how 2.3 THz radiation affects metabolic pathways and membrane-associated signaling in human melanoma cells.

SK-MEL-28 melanoma cells were exposed to 2.3 THz radiation for 45 min using the 1st Novosibirsk free-electron laser. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and trypan blue assays. Metabolic alterations were detected by targeted metabolomics using liquid chromatography–tandem mass spectrometry. Gene network analysis was performed using the ANDSystem platform to reconstruct gene and protein interaction networks linking altered metabolites to membrane receptors, lipid raft proteins, and signaling pathways. Overrepresentation analysis of biological processes was applied to identify enriched functional categories.

THz exposure did not affect cell viability but induced significant alterations in purine metabolism, pantothenate/CoA biosynthesis, and the pentose phosphate pathway. Network analysis revealed that these metabolic changes were associated with membrane raft reorganization and receptor-mediated signaling involving epidermal growth factor receptor and G-protein subunits. Additional effects were observed in pathways related to chromatin organization and post-translational regulation.

THz radiation induces coordinated remodeling of metabolic and regulatory networks in melanoma cells without cytotoxicity. These findings highlight the role of membrane-associated signaling in mediating THz-induced cellular responses and provide insight into potential biomedical applications of THz technologies.

Human immunodeficiency virus (HIV)/hepatitis C virus (HCV) coinfection leads to severe systemic inflammation, increasing non-AIDS morbidity and mortality risk. CD39 ectoenzyme on T-cells, which catalyzes the conversion of pro-inflammatory purines to immunosuppressive adenosine, plays an important role in inflammation control. The role of CD39+ T-cells in systemic inflammation during HIV/HCV coinfection under antiretroviral therapy (ART) remains unexplored. This study aimed to identify specific patterns of CD39 expression on T-cells in ART-treated HIV/HCV coinfected patients and assess their relationship with systemic inflammation.

We conducted a case-control study that enrolled 41 HIV/HCV coinfected patients on stable ART (cases) and 23 healthy controls. CD39 expression on blood CD4+ and CD8+ T-cells, including CD45RA+ and CD45RA– subsets, was quantified using flow cytometry. Cytokines were assessed using multiplex and enzyme-linked immunosorbent assays.

A significant proportion of CD4+ T-cells expressed CD39 in both groups (cases – 24.0%; controls – 16.1%). That was not true for CD8+ T-cells (cases – 3.2%; controls – 2.8%). CD39 expression was higher on CD45RA+ than CD45RA– CD4+ T-cells (cases – 39.4% vs. 19.0%; controls – 24.6% vs. 9.2%). HIV/HCV coinfected patients exhibited a significantly increased proportion of CD39+ CD4+ T-cells compared to uninfected controls (P < 0.01). A negative correlation was observed between the percentage of CD39+ CD4+ CD45RA– T-cells and levels of pro-inflammatory chemokines monocyte chemoattractant protein 1 (R = –0.392; P < 0.01) and eotaxin (R = –0.325; P < 0.05).

The data suggest a compensatory expansion of cells with regulatory properties that is ultimately insufficient to control systemic immune activation.

Colorectal cancer (CRC), like all other cancers, results from genetic and epigenetic alterations of the genome. The mechanisms leading to epigenetic alterations include DNA methylation, histone modifications, and small non-coding RNAs. As shown in many studies, some histone modifications such as acetylation, methylation, and phosphorylation are reported to be altered in CRC. Since these epigenetic alterations are reversible, they can be targeted as a strategy for CRC treatment. Numerous studies demonstrate the effects of molecules (both natural and synthetic) as inhibitors of enzymes responsible for histone acetylation, methylation, and phosphorylation in CRC cell lines. Some of these molecules have reached clinical trial stages. Vorinostat and belinostat, as histone deacetylase inhibitors; pinometostat and ribavirin, as histone methyltransferase inhibitors; and staurosporine and barasertib, which target histone phosphorylation, are among the promising epigenetic modifiers targeting histone alterations. Some of these modifiers can be used alone or in combination with other anticancer drugs or radiotherapy to increase efficacy. This review aims to identify molecules that target enzymes responsible for altering acetylation, methylation, and phosphorylation of histones in CRC.

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.

The genome editing technology based on clustered regularly interspaced short palindromic repeats/CRISPR-associated protein-9 (CRISPR/Cas9), is revolutionizing research, particularly in the context of human neurodegenerative disorders. This review examines recent advancements in CRISPR/Cas9 and its potential to address the protein misfolding mechanisms underlying these diseases. Proteins, the fundamental units of life, can misfold due to various changes, resulting in aggregation and contributing to devastating illnesses such as Alzheimer’s disease, Parkinson’s disease, Amyotrophic lateral sclerosis, and Huntington’s disease. Understanding the pathology of these disorders and the methods used for their detection is vital for developing effective treatments. CRISPR/Cas9 offers a powerful tool for combating neurodegenerative disorders at the molecular level. Its groundbreaking gene-editing capabilities are advancing preclinical and animal studies, paving the way for potential human trials and innovative therapeutic strategies. This review explores the complex challenge of protein misfolding and highlights how CRISPR technology could provide a crucial breakthrough in the fight against neurodegenerative disorders. It offers a synthesis of CRISPR advancements for neurodegenerative disorders. However, it is essential to be aware of the review’s limitations, including potential selection bias, the risk of oversimplification, and possible obsolescence in rapidly changing research fields. Despite these considerations, the transformative promise of CRISPR in understanding and potentially treating neurodegenerative diseases warrants continued research and thorough analysis.

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.