Cancer is now one of the major causes of death across the globe. Peptidylprolyl cis/trans isomerase, NIMA-interacting 1 (Pin1), has recently emerged as a critical factor in various cancers. Numerous studies have shown that Pin1 is highly expressed in several cancer types and is significantly associated with the prognosis of patients with a certain type of tumor such as gastric cancer. Meanwhile, some studies have indicated that infection with Helicobacter pylori significantly increases the risk of developing duodenal and gastric ulcer disease and gastric cancer. In this article, we propose that Pin1 can play a vital role in the prognosis of Helicobacter pylori infection-associated with peptic ulcer disease and can be effective in order to provide the best cure and the choice for treatment.

Background: Hepatitis C virus (HCV) may remain asymptomatic or cause liver fibrosis and cirrhosis. Objectives: We aimed to assess the relationship between serum peptidyl-prolyl cis-trans isomerase NIMA-interacted 1 (Pin1) levels and liver fibrosis due to HCV. Methods: Serum samples of successive patients with HCV genotype 1b and healthy volunteers were collected, and Pin1 levels were measured using ELISA kits. Liver fibrosis stages were calculated by the Ishak Scoring System and subdivided into two groups,stage < 3 (mild fibrosis) and,3 (advanced fibrosis). Correlation and area under receiver operating characteristics (AUROC) analysis were used to investigate the relationship between Pin1 and clinical and histopathological properties of HCV infection. Results: Ninety-four patients with HCV and 47 age-and sex-matched volunteers were included. The median age of the participants was 52, and 55% of whomwere females. The mean (SD) of Pin1 serum level was significantly higher in the HCV group compared with healthy volunteers (33. 94 (21. 15) vs. 26. 82 (8. 85) pg/mL, respectively, P = 0. 007). Seventy-seven (82%) and 17 (18%) of the participants showed mild and advanced fibrosis, respectively. Pin1 serum levels were significantly lower in the mild compared with advanced fibrosis group (29 (17. 88) vs. 43. 59 (7. 98) pg/mL, respectively, P < 0. 001). We found a significantly positive correlation between Pin1 serum level and liver fibrosis stage (r = 0. 71, P < 0. 001). The cut off of 33. 04 pg/mL of Pin1 serum level showed the best sensitivity (100%) and specificity (68. 4%) (AUROC = 0. 81 [95% confidence interval: 0. 72-0. 90], P < 0. 001) for distinguishing advanced from mild liver fibrosis. Conclusions: Serum Pin1 level may be a relevant marker for predicting liver fibrosis in HCV infected patients.

Background and Objective: In neurodegenerative disorders, oxidative stress mediated by reactive oxygen species is strongly associated with increased neuronal damages that lead to apoptosis. Pro-apoptotic and anti-apoptotic gene expressions were changed during cell differentiation that affect cell viability and differentiation. This study was conducted to determine the effects of hydrogen peroxide-induced oxidative stress on apoptotic cell death in the differentiated rat pheochromocytoma (PC12) cells.Materials and Methods: Semi-differentiated PC12 cells were treated with 400 μM hydrogen peroxide. Characteristic morphological changes as anapoptotic index were evaluated by DAPI staining. MTT assay were used to evaluate cells survival and activity. Pro-apoptotic and anti-apoptotic gene expression were estimated by real time-PCR.Results: The obtained data indicate that PC12 cell survival rate decreases in H2O2-treated condition during differentiation. Also, H2O2 increases apoptotic genes expressions including caspase 6 and Pin1 and decreases anti-apoptotic genes including sirt1 and sirt7.Conclusion: H2O2-induced oxidative stress can retard the differentiation of PC12 cell to neural-like cells through the apoptotic gene expression. On the other hand, despite the Pin1 acts as an apoptotic gene, this study illustrated that the expression of this gene is increased during differentiation under oxidative stress conditions.

Background: Colorectal cancer (CC) is one of the most prevalent cancers globally. Due to the severe side effects and the development of drug resistance in CC treatments, current therapeutic strategies often prove ineffective. As a result, there is a growing interest in exploring traditional medicinal plants as alternative treatment options for various human diseases. Diosgenin, a bioactive compound derived from plants, has shown potential in inhibiting the growth of human CC cells. The Wnt/β-catenin signaling pathway plays a critical role in colorectal tumorigenesis. Objectives: This study investigates the effects of Diosgenin on the Wnt/β-catenin pathway in CC cells. Methods: Colorectal cancer cells were treated with Diosgenin, and cell viability and plasma membrane integrity were assessed using the MTT assay and lactate dehydrogenase (LDH) activity assay, respectively. Apoptosis was evaluated through Annexin V/PI staining. The expression of Wnt/β-catenin-related genes was analyzed by quantitative PCR (qPCR). Results: Diosgenin significantly inhibited CC cell viability in a time- and concentration-dependent manner after 24, 48, 72, and 96 hours of exposure (P < 0.05). The IC50 values were determined to be 203.55, 122.95, 70.11, and 7.34 µM at 24, 48, 72, and 96 hours, respectively. Diosgenin at its IC50 concentration induced a significant increase in cell apoptosis after 24 hours of treatment (P < 0.05). Additionally, it caused a significant reduction in the expression of β-catenin, cyclin D1, and Pin1 (βCP). Conclusions: Diosgenin exhibits anti-CC effects by inhibiting the expression of βCP genes involved in the Wnt/β-catenin pathway, suggesting its potential as a therapeutic agent for CC.

Background: The conservative character of the cell cycle outlined that any dysregulation in the regulatory components of this process in normal cells opens a gate toward neoplastic transformation. Objectives: Given the critical role of cyclin-dependent kinases (CDKs) in cancer pathogenesis and based on their frequent aberrancy in human leukemia, the present study aimed at evaluating the suppressive effect of a multi-CDK inhibitor AT7519 on acute myeloid leukemia-derived U937 cells. Methods: To assess the anti-leukemic effects of the inhibitor on acute myeloid leukemia (AML) cells, we used MTT and trypan blue assays. Flow cytometric analysis and q-RT-PCR were also applied to evaluate the impact of AT7519 on cell cycle and apoptosis. Results: The results suggested that suppression of CDK in U937 cells hampered the proliferation of leukemic cells through a G2/M arrest mediated by p21 gene. Additionally, the anti-survival impact of AT7519 on these cells was shown to be along with the apoptosis initiation not only through the increment of pro-apoptotic gene expression but also through diminishing the mRNA levels of both Pin1 and Survivin. Notably, the potent anti-leukemic property of this agent has become more prominent when we found that the blockage of CDKs in AML cells could synergize with the cytotoxic effect of vincristine (VCR). To the best of our knowledge, little is known about the molecular mechanisms of resistance to AT7519 and we proposed that the effectiveness of this agent was partially attenuated through either c-Myc or autophagy activation in U937 cells. Conclusions: This study suggests that the pharmacological targeting of CDKscould probablyunwindthe complexity of therapeutic obstacles on the way of acute leukemia, either in the context of mono-or combined-modal strategy.