Regulating Inflammation Associated Ferroptosis - A Treatment Strategy for Parkinson Disease.

Ferroptosis plays a critical regulatory role as a new kind of cell death, initiating and developing an array of disorders like neurological diseases, acute injury of kidney, tumors, and ischemia, etc. Although selective deposition of iron is one of the pathogenic reasons for PD, it's underlying mechanism is still unknown. In this review, the role of neuroinflammation in Parkinson's disease (PD) leading to neurodegeneration has been discussed in detail. The accumulation of brain iron has been found in many chronic neurological disorders, including PD. We have also discussed the unique features of ferroptosis , and it links in aggravating the pathology of PD. Further, the concept of targeting ferroptosis for PD pathology and inducers and inhibitors, pharmacological drugs and clinical trials for PD candidates in phase IV stage in completed status are detailed in the respective sections.

Increased Expression of p-GSK3ß Predicts Poor Survival in T -III/IV Stage OSCC Patients.

BACKGROUND/AIM: Glycogen synthase kinase 3 beta (GSK3-ß) acts either as a tumor suppressor or an oncogene in various human cancers. The present study aimed to investigate the expression and activity of p-GSK3-ß (Ser9) in oral cancer patients. MATERIALS AND METHODS: We investigated the levels of p-GSK3ß in 152 oral cancer tissues by immunohistochemistry, and explored their prognostic impact. RESULTS: To investigate the role of p-GSK3ß (Ser9) in OSCC progression, we first analyzed the expression levels of protein p-GSK3ß in normal and oral cancer tissues using immunohistochemical staining. p-GSK3ß immunostaining was detected in 32 of 152 (21.1%) oral cancer specimens. High p-GSK3ß expression was significantly associated with T (III/IV) stage. Kaplan-Meier survival analysis revealed that high levels of p-GSK3ß were correlated with poor survival (p=0.001) in T stage (III/IV) OSCC patients. Multivariate analyses indicated that TN stage, AJCC tumor stage, tumor differentiation status and clinical therapy, but not p-GSK3ß levels, were independent prognostic factors. Significant mortality risk was found in T stage (III/IV) oral cancer patients with high levels of p-GSK3ß (p=0.0006). CONCLUSION: GSK3ß inactivation is a key event in oral cancer patients and targeting GSK3ß might be valuable in treating oral cancer patients.

Chemoresistance-Associated Silencing of miR-4454 Promotes Colorectal Cancer Aggression through the GNL3L and NF-κB Pathway.

Guanine nucleotide-binding protein-like-3-like (GNL3L) is a crucial regulator of NF-κB signaling that is aberrantly activated during diverse chemoresistance-associated cellular processes. However, the molecular mechanisms of GNL3L tumor initiation and resistant state are largely unknown. Moreover, the identification of predictive biomarkers is necessary to effectively generate therapeutic strategies for metastatic human colorectal cancer (CRC). This study aims to identify how cells acquire resistance to anticancer drugs and whether the downregulation of miR-4454 is associated with the progression of CRC. Here, we have shown that the overexpression of miR-4454 in resistant tumors is a crucial precursor for the posttranscriptional repression of GNL3L in human chemoresistant CRC progression, and we used doxycycline induced miR-4454 overexpression that significantly reduced tumor volume in a subcutaneous injection nude mice model. Together, these observations highlight that the downregulation of miR-4454 in resistant clones is prominently responsible for maintaining their resistance against anticancer drug therapy. Our study indicates that the development of miR-4454 as a microRNA-based therapeutic approach to silence GNL3L may remarkably reduce oncogenic cell survival that depends on GNL3L/NF-κB signaling, making miR-4454 a candidate for treating metastatic human CRC.