A decade in focus: mixed germ cell tumors with choriocarcinoma components.

Introduction: This 10-year registry review aimed to investigate the clinical behaviour and outcomes of mixed germ cell tumours with choriocarcinoma components, a rare and aggressive subtype of testicular cancer, in Saudi Arabia. The study explores the demographic characteristics of affected patients, tumour profiles, and the mortality rate associated with this malignancy. Methods: Utilizing data from the Saudi Cancer Registry, the authors identified 33 cases of mixed germ cell tumours with choriocarcinoma components among 1001 testicular cancer cases recorded between 2008 and 2017. Demographic information, including age, marital status, region of residency, year of diagnosis, and 10-year survival status, were collected. Tumour factors, such as the basis of diagnosis, origin site, behaviour, grade, extension, and laterality, were also analyzed. Results: The majority of cases (78.8%) occurred in the young age group (18-45 years), and most tumours (97%) originated in normally descended testes. Grade IV (undifferentiated anaplastic) tumours and distant metastasis were present in 45.5% of patients. All cases exhibited malignant tumour behaviour. The overall mortality rate was 15%, with a mean time from diagnosis to death of 7.72 months (range: 0.5-21.5 months). Conclusion: Mixed germ cell tumours with choriocarcinoma components are rare and tend to affect younger populations. These tumours demonstrate aggressive clinical behaviour, with a significant proportion presenting with high-grade lesions and metastasis at diagnosis. The observed mortality rate underscores the poor prognosis associated with this malignancy. Our study provides essential insights into the clinical characteristics of this rare tumour subtype in the Saudi Arabian population, emphasizing the need for further research to identify prognostic factors and optimize management strategies for affected patients.

Atherosclerosis Potential Drug Targets: Current Scenario and Future Perspectives.

BACKGROUND: The global burden of atherosclerosis and its implication to cause coronary heart disease and ischemic cardiac problems is the most prevalent cause of morbidity and hospitalization. In the US, there has been an increase in the number of patients with cardiac problems in the last decade, and still remains the primary cause of death in Europe as well as in the US. OBJECTIVES: Even though therapeutic interventions and early diagnosis the formation of the fatty lesion and its subsequent steps are possible, the therapeutic management of the disease remains questionable when clinical data is observed. There is still scope for proper target identification and biomarker recognition, which can serve as a baseline to develop efficient pharmacological agent and delivery systems so that the disease incidence and prevalence can be controlled. The present article highlights the current pathophysiological state of the disease and emerging strategies that are applied to manage the disease. FINDINGS: This article gives an insight into the limitations of various conventionally used therapeutic agents for disease treatment. The emerging strategies that could prove efficacious in disease treatment. This article also gives an insight into current discoveries in the field of cellular and molecular biology, such as the genetic role in causing dyslipidemia and the role of immune cells and the role of non-coding small RNA, which can set the future direction to develop therapeutics interventions for atherosclerosis.

The Mediating Impact of IT Capabilities on the Association between Dynamic Capabilities and Organizational Agility: The Case of the Jordanian IT Sector.

This study suggests a novel progression to the current research endeavor by investigating the influence of information technology capabilities on organizational agility. More specifically, this study aims to fill the gaps found in previous studies and contribute to the current state of knowledge of this domain by focusing on the mediating role that IT capabilities play between dynamic capabilities and organizational agility. Toward that end, 270 Jordanian professionals working in supply chain management and operational departments were approached. Data were collected via distrusting a structured questionnaire that includes items assessing dynamic capabilities, IT capabilities, and organizational agility. The results demonstrated that IT capabilities significantly and positively mediated the relationship between resource-based dynamic capability and organizational agility. The study has also discussed several theoretical along with managerial implications of the research.

Evaluation of pyrazolopyrimidine derivatives as microtubule affinity regulating kinase 4 inhibitors: Towards therapeutic management of Alzheimer's disease.

Microtubule affinity regulating kinase 4 (MARK4) plays essential role in the tau-assisted regulation of microtubule dynamics. Over expression of MARK4 causes early phosphorylation of Ser262 of tau protein which is essential for microtubule binding. Hyperphosphorylation of tau protein causes the formation of paired helical fragments and neurofibrillary tangles, the hallmarks of Alzheimer's disease. Targeting the modulation of MARK4 activity is an effective strategy for therapeutic intervention of Alzheimer's and other MARK4 associated neurodegenerative diseases. Having role of pyrazolopyrimidine derivatives in the therapeutic management of neurodegenerative diseases, we have tried to estimate their binding affinity with the MARK4. We performed in silico screening of 59 pyrazolopyrimidine derivatives against MARK4 and obtained a few best possible inhibitors. Molecular docking-based interaction analysis suggested five potential leads that were further analyzed using molecular dynamics simulations, MM/PBSA, principal component analysis and graph theory based dynamic network analysis to observe structural changes caused due to ligand binding. All these computational analyses suggested that compounds with PubChem IDs: 91895678, 91895679, 91895692, 91145515 and 90794095 may be further exploited to address Alzheimer's and other neurodegenerative diseases.Communicated by Ramaswamy H. Sarma.

Evaluation of binding and inhibition mechanism of dietary phytochemicals with sphingosine kinase 1: Towards targeted anticancer therapy.

Sphingosine kinase 1 (SphK1) has recently gained attention as a potential drug target for its association with cancer and other inflammatory diseases. Here, we have investigated the binding affinity of dietary phytochemicals viz., ursolic acid, capsaicin, DL-α tocopherol acetate, quercetin, vanillin, citral, limonin and simvastatin with the SphK1. Docking studies revealed that all these compounds bind to the SphK1 with varying affinities. Fluorescence binding and isothermal titration calorimetric measurements suggested that quercetin and capsaicin bind to SphK1 with an excellent affinity, and significantly inhibits its activity with an admirable IC50 values. The binding mechanism of quercetin was assessed by docking and molecular dynamics simulation studies for 100 ns in detail. We found that quercetin acts as a lipid substrate competitive inhibitor, and it interacts with important residues of active-site pocket through hydrogen bonds and other non-covalent interactions. Quercetin forms a stable complex with SphK1 without inducing any significant conformational changes in the protein structure. In conclusion, we infer that quercetin and capsaicin provide a chemical scaffold to develop potent and selective inhibitors of SphK1 after required modifications for the clinical management of cancer.