HN1 expression contributes to mitotic fidelity through Aurora A-PLK1-Eg5 axis.

Hematological and neurological expressed 1 (HN1) is homolog of Jupiter protein from Drosophila melanogaster where it functions as a microtubule-associated protein. However, in mammalian cells, HN1 is associated partially with y-tubulin in centrosomes, Stathmin for stabilizing microtubules, and Cdh1 for regulating Cyclin B1 for cell cycle regulation. Moreover, HN1 overexpression leads to early mitotic exit as well. Other molecular functions and interactions of HN1 are not clear yet. Here, based on our previous analysis where HN1 was shown to cluster supernumerary centrosomes and maintain mitotic spindle assembly, we further investigated the role of HN1 in centrosome maintenance and mitotic fidelity in PC-3 prostate and MDA-MB231 mammary cancer cell lines. The maturation-associated roles of HN1 during cell division by examining the AuroraA-PLK1 axis involving a plus end kinesin, Eg5 as well as pericentriolar matrix protein (PCM1) as components of centrosomes were established. We found that HN1 co-localized to centrioles with Eg5 and Aurora A to suppress aberrant spindle formation to ensure the fidelity of centriole/centrosome duplication when overexpressed. Consistently, depleting the HN1 expression using siRNA or shRNA resulted in an increased number of dysregulated mitotic spindle structures, where Aurora A as well as PLK1 co-localizations with Eg5 and PCM1 were disrupted. Further, the PLK1 and Aurora A kinase's phosphorylations also decreased, confirming the hypothesis that the cells struggle in mitotic progression, display nuclear and cytokinetic abnormalities with supernumerary but immature mononucleated centrosomes. In summary, we described the role of HN1 in centrosome nucleation/maturation in PLK1-Eg5 axis and concomitant mitotic spindle formation in human cells.

The role of Ottawa ankle rules in geriatric emergency department visits.

BACKGROUND: Ankle injuries are a common reason for visits to the emergency department (ED). An effective diagnosis and treatment process is crucial for the swift recovery of patients and for alleviating congestion in EDs. This study aims to evaluate the adequacy and effectiveness of the Ottawa Ankle Rules (OAR) in geriatric patients presenting to the emergency department (ED). METHODS: Between February 2022 and November 2022, 160 patients aged 65 and older (118 women, 42 men) who presented to the ED with isolated ankle injuries were included in the study. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value of the OAR. RESULTS: The study found fractures in 37.5% of patients. The sensitivity of the OAR was 98.33%, the specificity was 86%, the negative predictive value was 98.85%, and the positive predictive value was 80.82%. CONCLUSION: This study demonstrates that the OAR is highly sensitive in the geriatric population but shows some limitations in terms of specificity and positive predictive value. These results support the effectiveness of using the OAR in evaluating ankle injuries in the geriatric population but also highlight the need for cautious application due to the potential for false-positive outcomes.

Mitotic kinase inhibitors as Therapeutic Interventions for Prostate Cancer: Evidence from In vitro Studies.

Prostate cancer is one of the devastating diseases characterized by genetic changes leading to uncontrolled growth and metastasis of the cells of the prostate gland and affects men worldwide. Conventional hormonal and chemotherapeutic agents are effective in mitigating the disease if diagnosed at an early stage. All dividing eukaryotic cells require mitotic progression for the maintenance of genomic integrity in progeny populations. The protein kinases, upon activation and de-activation in an ordered fashion, lead to spatial and temporal regulation of the cell division process. The entry into mitosis along with the progression into sub-phases of mitosis is ensured due to the activity of mitotic kinases. These kinases include Polo-Like-Kinase 1 (PLK1), Aurora kinases, and Cyclin-Dependent-Kinase 1 (CDK1), among others. The mitotic kinases, among others, are usually overexpressed in many cancers and can be targeted using small molecule inhibitors to reduce the effects of these regulators on mechanisms, such as regulation of genomic integrity and mitotic fidelity. In this review, we attempted to discuss the appropriate functions of mitotic kinases revealed through cell culture studies and the impact of their respective inhibitors derived in pre-clinical studies. The review is designed to elucidate the growing field of small molecule inhibitors and their functional screening or mode of action at the cellular and molecular level in the context of Prostate Cancer. Therefore, studies performed specifically on cells of Prostatic-origin are narrated in this review, culminating in a comprehensive view of the specific field of mitotic kinases that can be targeted for therapy of Prostate cancer.