Oxidative Stress in Liver Pathophysiology and Disease.

The liver is an organ that is particularly exposed to reactive oxygen species (ROS), which not only arise during metabolic functions but also during the biotransformation of xenobiotics. The disruption of redox balance causes oxidative stress, which affects liver function, modulates inflammatory pathways and contributes to disease. Thus, oxidative stress is implicated in acute liver injury and in the pathogenesis of prevalent infectious or metabolic chronic liver diseases such as viral hepatitis B or C, alcoholic fatty liver disease, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH). Moreover, oxidative stress plays a crucial role in liver disease progression to liver fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Herein, we provide an overview on the effects of oxidative stress on liver pathophysiology and the mechanisms by which oxidative stress promotes liver disease.

MicroRNAs in esophageal squamous cell carcinoma: Application in prognosis, diagnosis, and drug delivery.

MicroRNAs (miRNAs) play a vital role in various cell biology processes, including cancer formation. These small non-coding RNAs could function as diagnostic and prognostic markers. They may involve esophageal squamous cell carcinoma (ESCC) and distinctive miRNA expression profiles; they are also known as therapeutic targets in human diseases. Therefore, in this study, the function of miRNAs was reviewed regarding the prognosis and diagnosis of ESCC. The changes in miRNAs before and after cancer therapy and the effects of miRNAs on chemo-susceptibility patterns were also investigated. MiRNA delivery systems in ESCC were also highlighted, providing a perspective on how these systems can improve miRNA efficiency.

Melatonin: A smart molecule in the DNA repair system.

DNA repair is an important pathway for the protection of DNA molecules from destruction. DNA damage can be produced by oxidative reactive nitrogen or oxygen species, irritation, alkylating agents, depurination and depyrimidination; in this regard, DNA repair pathways can neutralize the negative effects of these factors. Melatonin is a hormone secreted from the pineal gland with an antioxidant effect by binding to oxidative factors. In addition, the effect of melatonin on DNA repair pathways has been proven by the literature. DNA repair is carried out by several mechanisms, of which homologous recombination repair (HRR) and non-homologous end-joining (NHEJ) are of great importance. Because of the importance of DNA repair in DNA integrity and the anticancer effect of this pathway, we presented the effect of melatonin on DNA repair factors regarding previous studies conducted in this area.

Crosslink between p53 and metastasis: focus on epithelial-mesenchymal transition, cancer stem cell, angiogenesis, autophagy, and anoikis.

INTRODUCTION: P53, as a tumor suppressor gene, is believed to be one of the most mutated genes in cancer cells. The mutant forms of this protein often play a tumorigenic role in cancer cells. Recent evidence shows that p53 plays a critical role in the migration, metastasis, and invasion of cancer cells. The present article aims to investigate the molecular mechanism that induces metastasis in cancer cells generated by the mutant P53, and to highlight the compounds targeting mutant-p53 together with their clinical applications. METHODS: A detailed literature search was conducted to find information about the role of the mutant-p53 in the processes involved in metastasis in various databases. RESULTS: A growing body of evidence suggests that Mutant-p53 enhances tumor metastasis affecting the Epithelial-mesenchymal transition (EMT) process, cancer stem cells, angiogenesis, autophagy, anoikis, and any other mechanisms regarding metastasis. CONCLUSIONS: Taken together, targeting mutant-p53 by altering the processes involved in metastasis could be a potential therapeutic strategy in the treatment of metastatic cancer.

Nitric oxide, 8-hydroxydeoxyguanosine, and total antioxidant capacity in human seminal plasma of infertile men and their relationship with sperm parameters.

OBJECTIVE: Oxidative stress plays a key role in the pathogenesis of male infertility. But, the adverse effects of oxidative biomarkers on sperm quality remain unclear. This study aimed to investigate the levels of nitric oxide (NO), 8-hydroxydesoxyguanosine (8-OHdG), and total antioxidant capacity (TAC) oxidative biomarkers in seminal plasma and their relationship with sperm parameters. METHODS: A total of 77 volunteers participated in the study, including fertile (n=40) and infertile men (n=37). NO, 8-OHdG, and TAC levels were measured using the ferric reducing ability of plasma, Griess reagent method and an enzyme-linked immunosorbent assay kit, respectively. RESULTS: The mean values of sperm parameters in the infertile group were significantly lower than those in the fertile group (p<0.001). The mean 8-OHdG in the seminal plasma of infertile men was significantly higher (p=0.013) than those of controls, while the mean TAC was significantly lower (p=0.046). There was no significant difference in NO level between the two groups. The elevated seminal 8-OHdG levels were negatively correlated with semen volume, total sperm counts and morphology (p<0.001, p=0.001 and p=0.052, respectively). NO levels were negatively correlated with semen volume, total sperm counts and morphology (p=0.014, p=0.020 and p=0.060, respectively). Positive correlations between TAC and both sperm count and morphology (p=0.043 and p=0.025, respectively) were also found. CONCLUSION: These results suggested that increased levels of NO and 8-OHdG in seminal plasma could have a negative effect on sperm function by inducing damage to the sperm DNA hence their fertility potentials. Therefore, these biomarkers can be useful in the diagnosis and treatment of male infertility.

Application of sesquiterpene lactone: A new promising way for cancer therapy based on anticancer activity.

Cancer is one of the most dangerous diseases that are rapidly increasing globally. After heart disease, it is the second leading cause of death, accounting for seven million deaths each year. Chemotherapy is the use of cytotoxic drugs on cancer cells. But the use of common chemotherapy drugs poses a problem due their high side effects and low efficacy. As a result, efforts are on to find new potent compounds with low side effects. The compounds extracted from plants have been studied in this regard due to their prevalence. Sesquiterpene lactones are a group of natural compounds that were first detected in Asteraceae dark plants. These compounds exercise their effects by reacting with functional groups available on proteins and enzymes, especially the thiol group. Owing to the high side effects as an antitumor synthetic drugs, efforts are being made to find drugs with high efficiency and low side effects. Their high structural ranges have attracted the attention of many researchers as a potential source of new anticancer drugs.