The overwhelming majority of genes in the human genome encode RNA molecules that are not translated into proteins. These RNA molecules are named non-coding RNAs (ncRNAs). ncRNAs play a crucial role in the regulation of gene expression and abnormalities in ncRNAs can cause disease progression, including atherosclerosis. ncRNAs regulate different stages of atherosclerosis progression, such as foam cell formation and lipid metabolism. Diverse types of ncRNAs have been studied, but the best known and widely used are small non-coding (sncRNAs), specifically microRNAs and small interfering RNAs, which are ∼22 nucleotides long. The majority of drugs based on ncRNAs are composed of sncRNAs. There is strong evidence that besides sncRNAs, other types of ncRNAs, such as long ncRNAs and circular RNAs, take part in the regulation of gene expression. This review summarized recent advances in ncRNAs and atherosclerosis.

Breast cancer is the most prevalent malignancy and the leading cause of cancer-related death in women. Breast cancer is still an extremely difficult cancer to treat due to its significant metastasis. Mis-regulation of Notch signaling components such as Notch receptors/ligands and their interaction in breast cancer sparks tumor initiation, maintenance, and progression through induction of abnormal tumorigenesis while modulating vascular integrity, drug resistance, invasion, and migration. Numerous studies have shown that non-coding RNAs can regulate Notch signaling and accordingly impact breast cancer pathobiology. MiRNAs could regulate Notch signaling components directly or indirectly via sponging or suppressing other genes involved in the pathway. Further, lncRNAs interact with miRNAs and mRNAs, and lncRNA-miRNA-mRNA interaction networks function as substantial mediators in various pathways, including the Notch signaling pathway. Also, by targeting and sponging other genes, circRNAs could induce tumorigenic properties via the Notch signaling pathway. Due to the intricacy of human physiology, it is challenging for standard drugs to be effective, and cancer cells can develop resistance to treatment and have a significant self-renewal capacity. Moreover, because non-specific Notch signaling intervention targets both tumor cells and immune cells, it may have the reverse effect of regulating the formation of tumors. Thus, an in-depth understanding of the mechanisms could be useful in diagnosis, prognosis, and the development of novel medications that specifically target Notch signaling, improving the efficacy of cancer immunotherapy in the treatment of breast cancer. This review will discuss and clarify the mechanisms by which miRNAs, lncRNAs, and circRNAs affect the Notch signaling pathway leading to BC development.

Non-alcoholic fatty liver disease (NAFLD) is an extremely prevalent disease, and the presence and severity of liver fibrosis are considered one of the most important factors determining its prognosis. Hepatic stellate cells (HSCs) are essential in hepatic fibrogenesis associated with NAFLD. A number of factors underlying NAFLD pathogenesis may promote HSCs activation, leading to the development of profibrotic and proinflammatory signs. In addition, for the fibrogenic transdifferentiation of quiescent HSCs, alterations in multiple genes are necessary, where epigenetic regulation plays a defining role. Epigenetic regulation induces changes in gene activity without altering the coding sequence, and these changes are stably inherited after the factor causing the alteration has disappeared. Epigenetic modifications comprise several regulatory mechanisms, including DNA methylation, covalent histone modification, chromatin remodeling, and non-coding RNAs. Since the mechanisms underlying epigenetic regulation of HSCs fibrogenic activation are reversible and dynamic, molecular targeted therapies aimed at correcting these mechanisms provide promising prospects for novel therapeutic approaches for treating liver fibrosis associated with NAFLD.

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.

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.

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.

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are the leading causes of hepatic fibrosis and liver-related mortality worldwide, despite efficient hepatitis B and C antiviral therapies that have dramatically lowered the disease load. Although significant efforts have been exerted to understand the molecular basis of disease pathogenesis, there are currently few therapeutic alternatives available for NAFLD-associated fibrosis. Thus, NAFLD prevention is critical before the development of disease-related complications. In this context, there is a tremendous substantial global burden on public health systems to actively search for effective preventive and therapeutic targets for NAFLD. In this review, we highlight the current strategies to prevent progression and poor outcomes of NAFLD and to avoid complications associated with disease fibrosis, notably cirrhosis, portal hypertension, and liver cancer. We discuss different nonpharmacological measures, such as lifestyle modifications (weight loss, exercise, healthy diet) and other pharmacological interventions that could prevent NAFLD.

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.

Today, medicinal plants and phytobiotics that contain flavonoids, alkaloids, and essential oils are widely used in animal feed. These additives have many benefits, including increasing liver function and preventing certain diseases. The liver is one of the organs that plays a key role in insulin-mediated regulation of metabolism as well as in glucose, whole-body, and lipid homeostasis. The aim of this study was to investigate the effect of fennel (Foeniculum vulgare) seed powder consumption on insulin-like growth factor 1 (IGF1) gene expression in the liver tissue of growing lambs.

Three groups (including 0, 10, and 20 g/kg dry matter of fennel) of animals, with 10 animals in each group, were studied. The Pfaffl method was applied to assess the real-time polymerase chain reaction (qPCR) output.

Mixing fennel into the feed of lambs increased the weights of their testis and gallbladder and decreased the weight of their liver in comparison to feed without fennel. It was also found that by increasing the fennel level in the feed, the expression level of IGF1 in the liver increased significantly (p < 0.05).

Fennel has a useful effect on the expression of IGF1 in the liver tissue of sheep and may be applied to their diet to attain better liver function.