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c-Jun is often found to be overexpressed in various cancers, so this gene might be a target for cancer therapy. Newcastle disease virus (NDV) is recognized for its oncolytic properties and potential as a cancer virotherapy agent, with various mechanisms reported to trigger cancer cell death. This study aimed to assess the c-Jun expression in rat mammary cancer models. Rat mammary cancer models were categorized into two treatment groups: the control group (C) and the virotherapy group (V). Group C was administered with 0.5 cc of sterile PBS, while group V received 7 log 2 HAU per 0.5 cc of the Indonesian NDV field isolate Tabanan-1/ARP/2017 intratumorally. The treatment was carried out for four days in a row. Two weeks after treatment, all rats were humanely euthanized, and mammary cancer tissues were excised for further examination. Mammary cancer tissues were examined histopathologically and analyzed using immunohistochemistry to determine intranuclear cJun expression, quantified by the H-Score. The results demonstrated that NDV significantly reduced c-Jun expression. It can be inferred that NDV Tabanan-1/ARP/2017 holds potential as a mammary cancer therapy agent by reducing c-Jun expression. This finding is considered novel, as there have been no previous reports of decreased c-Jun expression following virotherapy with NDV. [ABSTRACT FROM AUTHOR]

The blood–brain barrier (BBB) is a complex structure that separates the central nervous system (CNS) from the peripheral blood circulation. Effective communication between different cell types within the BBB is crucial for its proper functioning and maintenance of homeostasis. In this study, we demonstrate that meningitic Escherichia coli (E. coli)-induced WNT5B plays a role in facilitating intercellular communication between astrocytes and brain microvascular endothelial cells (BMECs). We discovered that astrocytes-derived WNT5B activates the non-canonical WNT signaling pathway JNK/c-JUN in BMECs through its receptor ROR1, leading to inhibition of ZO-1 expression and impairment of the tight junction integrity in BMECs. Notably, our findings reveal that c-JUN, a transcription factor, directly regulates ZO-1 expression. By employing a dual luciferase reporting system and chromatin immunoprecipitation techniques, we identified specific binding sites of c-JUN on the ZO-1 promoter region. Overall, our study highlights the involvement of WNT5B in mediating intercellular communication between astrocytes and BMECs, provides insights into the role of WNT5B in meningitic E. coli-induced disruption of BBB integrity, and suggests potential therapeutic targeting of WNT5B as a strategy to address BBB dysfunction. [ABSTRACT FROM AUTHOR]

c-Jun is often found to be overexpressed in various cancers, so this gene might be a target for cancer therapy. Newcastle disease virus (NDV) is recognized for its oncolytic properties and potential as a cancer virotherapy agent, with various mechanisms reported to trigger cancer cell death. This study aimed to assess the c-Jun expression in rat mammary cancer models. Rat mammary cancer models were categorized into two treatment groups: the control group (C) and the virotherapy group (V). Group C was administered with 0.5 cc of sterile PBS, while group V received 7 log 2 HAU per 0.5 cc of the Indonesian NDV field isolate Tabanan-1/ARP/2017 intratumorally. The treatment was carried out for four days in a row. Two weeks after treatment, all rats were humanely euthanized, and mammary cancer tissues were excised for further examination. Mammary cancer tissues were examined histopathologically and analyzed using immunohistochemistry to determine intranuclear c-Jun expression, quantified by the H-Score. The results demonstrated that NDV significantly reduced c-Jun expression. It can be inferred that NDV Tabanan-1/ARP/2017 holds potential as a mammary cancer therapy agent by reducing c-Jun expression. This finding is considered novel, as there have been no previous reports of decreased c-Jun expression following virotherapy with NDV.

Inflammatory pain is a pervasive clinical issue that severely diminishes individuals' quality of life. AP-1 (Activating protein-1) is a transcription factor composed of Jun and Fos proteins. Upregulation of AP-1/c-Jun activity is observed in a variety of diseases, particularly in inflammatory conditions. The CCL2 (C-C Motif Chemokine Ligand 2)/CCR2 (C-C Chemokine Receptor 2) axis plays a crucial role in regulating both peripheral and central inflammation. Curcumin, a natural compound derived from the roots of turmeric, possesses anti-inflammatory, antioxidant, and analgesic properties, making it effective for treating various disorders. However, the effects of curcumin on inflammatory pain and its potential mechanisms of action remain unclear. In this study, we utilized a CFA (Complete Freund's Adjuvant)-induced inflammatory pain model to investigate the effects of curcumin. We found that curcumin effectively reduced CFA-induced mechanical allodynia when administered via intrathecal injection. Behavioral assessments were performed using the Von Frey test. Western blot analysis was performed to detect variations in molecular expression, while immunofluorescence was employed to ascertain cellular localization. Intrathecal injection of the AP-1/c-Jun inhibitor T-5224, along with curcumin, resulted in a reduction in the levels of c-Jun, p-c-Jun, CCL2, and CCR2. Additionally, intrathecal injection of the CCR2 antagonist RS504393 also reduced the expression of CCL2 and CCR2. In summary, curcumin plays a significant role in analgesia within the CFA-induced inflammatory pain model. CCL2/CCR2 acts as a downstream mediator of AP - 1/c - Jun. Curcumin can suppress the expression of AP - 1/c - Jun, thereby inhibiting the expression of CCL2 and CCR2 in the spinal dorsal horn and contributing to the treatment of inflammatory pain.

Cervical cancer remains a significant global health concern. KIF18A, a kinesin motor protein regulating microtubule dynamics during mitosis, is frequently overexpressed in various cancers, but its regulatory mechanisms are poorly understood. This study investigates KIF18A's role in cervical cancer and its regulation by the JNK1/c-Jun signaling pathway. Cell growth was assessed in vitro using MTT and colony formation assays, and in vivo using a nude mouse xenograft model with KIF18A knockdown HeLa cells. The Genomic Data Commons (GDC) data portal was used to identify KIF18A-related protein kinases in cervical cancer. Western blot analysis was employed to analyze phosphor-c-Jun, c-Jun, and KIF18A expression levels following JNK1 inhibition, c-Jun knockdown/overexpression, and KIF18A knockdown in cervical cancer cells. Chromatin immunoprecipitation (ChIP) and luciferase reporter assays were performed to assess c-Jun binding and transcriptional activity of the KIF18A promoter. KIF18A knockdown significantly impaired cervical cancer cell growth both in vitro and in vivo. A strong positive correlation was observed between JNK1 and KIF18A expression in cervical and other cancers. JNK1 inhibition decreased both KIF18A expression and c-Jun phosphorylation. c-Jun was found to directly bind to and activate the KIF18A promoter. Furthermore, c-Jun knockdown inhibited cervical cancer cell growth, and this effect was partially rescued by KIF18A overexpression. This study demonstrates that the JNK1/c-Jun pathway activates KIF18A expression, which is essential for cervical cancer cell growth. Targeting the JNK/c-Jun/KIF18A axis may represent a promising novel therapeutic strategy for cancer treatment., (© 2024 Wiley Periodicals LLC.)