Discovery of AZD8421: A Potent CDK2 Inhibitor with Selectivity Against Other CDK Family Members and the Human Kinome.

Targeting CDK2 with first generation CDK2 inhibitors suffered from a reduced therapeutic index likely due to toxicity stemming from lack of selectivity against the CDK family and other kinases. Recently, CDK2 has been identified as a mediator of resistance to CDK4/6 inhibitors in the context of high levels of cyclin E expression. Discovery of highly selective CDK2 inhibitors may minimize off-target effects, reduce toxicity observed with first generation CDK2 inhibitors, and allow precise targeting of aberrant cell cycle progression and resistance mechanisms mediated by high cyclin E/CDK2 activity.

The Role of Colchicine in Plant Breeding.

Colchicine, a strong antimitotic drug produced by the crocus , induces polyploidy by interfering with spindle formation during mitosis, making it a crucial tool in plant breeding. In this review, we give a comprehensive overview of the function of colchicine in plant enhancement, emphasizing its modes of action, application techniques, and effects on phytochemistry, physiology, and plant morphology. A wide variety of plant species, especially medicinal plants, have been studied in this context, utilizing in vitro, ex vitro, and in vivo methods for applying colchicine.

Advances in Breast Cancer Detection: Biomarkers, Mechanisms, and Biosensor Technologies.

Breast cancer (BC), the most common cancer in women, remains a global health concern. According to the World Health Organization, in the year 2022, BC caused around 6,70,000 deaths. This huge mortality number requires immediate attention and intervention in the form of early diagnosis and therapies.

Global, Regional, and National Burden of Nontraumatic Subarachnoid Hemorrhage: The Global Burden of Disease Study 2021.

Importance: Nontraumatic subarachnoid hemorrhage (SAH) represents the third most common stroke type with unique etiologies, risk factors, diagnostics, and treatments. Nevertheless, epidemiological studies often cluster SAH with other stroke types leaving its distinct burden estimates obscure.

Objective: To estimate the worldwide burden of SAH.

Enhancing Food Quality Analysis: The Transformative Role of Artificial Neural Networks in Modern Analytical Techniques.

Background: Consumers have always anticipated and requested high-quality and safe food items, which is why food quality analyses and mandatory product inspections were introduced. Various novel techniques and analytical breakthroughs have emerged to cater to the problem of food authenticity. It is difficult to interpret and analyze large and complex data with traditional machine learning algorithms.

Detection of Extramedullary Laryngeal Involvement on 68 Ga-Pentixafor PET/CT in a Newly Diagnosed Patient of Multiple Myeloma.

A 40-year-old man with newly diagnosed multiple myeloma underwent both 68 Ga-Pentixafor and 18 F-FDG PET/CT. Extramedullary laryngeal involvement was noted on both modalities in addition to diffuse marrow involvement and focal lesions. 68 Ga-Pentixafor PET/CT is increasingly used in multiple myeloma and demonstrates similar diagnostic performance as 18 F-FDG PET/CT.

68 Ga-Pentixafor PET/CT-Based Response Evaluation and its Prognostic Value in Multiple Myeloma: Comparison With IMWG and 18 F-FDG-Based Response.

Purpose: 68 Ga-Pentixafor PET/CT targets CXCR4 receptors and provides superior diagnostic accuracy in multiple myeloma (MM) compared with 18 F-FDG PET/CT. However, its role in response evaluation remains unexplored. We propose a 68 Ga-Pentixafor PET/CT-based response evaluation criterion and evaluate its utility compared with International Myeloma Working Group (IMWG) criteria and 18 F-FDG PET/CT-based response.

Can 99m Tc-PSMA SPECT/CT Presenting Mirror Image of 68 Ga-PSMA PET/CT Be Used for Response Assessment to 177 Lu-PSMA in Metastatic Castration-Resistant Prostate Cancer?

A 69-year-old man, with a known case of metastatic castration-resistant prostate cancer (mCRPC) underwent 68 Ga-PSMA PET/CT and 99m Tc-PSMA for evaluation of disease burden and response assessment to 177 Lu-PSMA therapy. 99m Tc-PSMA provided a mirror image of 68 Ga-PSMA. This suggests the potential of 99m Tc-PSMA SPECT/CT for disease evaluation and response assessment to PSMA-based radioligand therapies in advanced-stage mCRPC patients, especially when 68Ga-PSMA PET/CT is not available.

Identification of Substituted 4-Aminocinnolines as Broad-Spectrum Antiparasitic Agents.

Neglected tropical diseases such as Chagas disease, human African trypanosomiasis, leishmaniasis, and schistosomiasis have a significant global health impact in predominantly developing countries, although these diseases are spreading due to increased international travel and population migration. Drug repurposing with a focus on increasing antiparasitic potency and drug-like properties is a cost-effective and efficient route to the development of new therapies. Here we identify compounds that have potent activity against and , and the latter were progressed into the murine model of infection.

Phytochemical strategies in glioblastoma therapy: Mechanisms, efficacy, and future perspectives.

Glioblastoma (GBM) is foremost the most aggressive primary brain tumor, presenting extensive therapeutic challenges due to its high invasiveness, genetic complexity, and resistance to established treatments. Despite substantial advances in surgical and chemotherapeutic interventions, the median survival rate for patients is only 14.6 months, and the prognosis remains poor.

Long-acting parenteral formulations of hydrophilic drugs, proteins, and peptide therapeutics: mechanisms, challenges, and therapeutic benefits with a focus on technologies.

Despite being the most widely prescribed formulation, oral formulations possess several limitations such as low adherence, low bioavailability, high toxicity (in the case of anticancer drugs), and multiple-time administration requirements. All these limitations can be overcome by long-acting injectables. Improved adherence, patient compliance, and reduced relapse have been observed with long-acting formulation which has increased the demand for long-acting injectables.

Current and Future Perspectives of PDL1 PET and SPECT Imaging.

Programmed Death 1 (PD1) and Programmed Death Ligand (PDL1) play a crucial role in tumor microenvironment by helping cancer cells evade innate immunity. Numerous inhibitor anticancer drugs targeting this interplay have been used in clinical practice and many more are in preclinical stage. These drugs have shown promising results in achieving good response and long-term clinical benefit, is routinely performed to identify patients who may benefit.

Unraveling the Clinical Complexity of Thyrotoxic Periodic Paralysis: A Case Report.

Thyrotoxic periodic paralysis (TPP) is a clinical condition characterized by hypokalemia, muscle paralysis, and hyperthyroidism. TPP can be challenging to diagnose due to its low disease prevalence and the similarity of paralysis to other common conditions. Through this case report, we highlight the importance of considering hyperthyroidism as a cause of recurrent attacks of muscle paralysis, particularly in the setting of other signs of hyperthyroidism.

MicroRNA164e suppresses NAC100 transcription factor-mediated synthesis of seed storage proteins in chickpea.

Development of protein-enriched chickpea varieties necessitates an understanding of specific genes and key regulatory circuits that govern the synthesis of seed storage proteins (SSPs). Here, we demonstrated the novel involvement of Ca-miR164e-CaNAC100 in regulating SSP synthesis in chickpea. Ca-miRNA164e was significantly decreased during seed maturation, especially in high-protein accessions.

68 Ga-Pentixafor PET/CT for In Vivo Imaging of CXCR4 Receptors in Glioma Demonstrating a Potential for Response Assessment to Radiochemotherapy: Preliminary Results.

Purpose: The aim of this study was to evaluate the diagnostic potential of 68 Ga-pentixafor PET/CT for in vivo CXCR4 receptors imaging in glioma and its possible role in response assessment to radiochemotherapy (R-CT).

Methods: Nineteen (12 men, 7 women) patients with glioblastoma multiforme (GBM) underwent 68 Ga-pentixafor PET/CT, contrast-enhanced MR, and MR spectroscopy. Patients were divided in to 2 groups, that is, group I was the presurgical (n = 9) group in which the scanning was done before surgery, and PET findings were correlated with CXCR4 receptors' density.

Alzheimer's disease current therapies, novel drug delivery systems and future directions for better disease management.

Alzheimer's disease (AD), is a neurodegenerative disorder that escalates with time, exerting a significant impact on physical and mental health and leading to death. The prevalence of AD is progressively rising along with its associated economic burden and necessitates effective therapeutic approaches in the near future. This review paper aims to offer an insightful overview of disease pathogenesis, current FDA-approved drugs, and drugs in different clinical phases.

Efficacy of Yttrium-90 Transarterial Radioembolisation in Advanced Hepatocellular Carcinoma: An Experience With Hybrid Angio-Computed Tomography and Glass Microspheres.

Background: Hepatocellular carcinoma is one of the most common malignancies worldwide. Transarterial radioembolisation (TARE) involves selective intra-arterial administration of microspheres loaded with a radioactive compound like Yttrium-90 (Y-90). Conventionally, C-arm-based cone-beam computed tomography has been extensively used during TARE.

Discovery, Optimization, and Biological Evaluation of Arylpyridones as Cbl-b Inhibitors.

Casitas B-lymphoma proto-oncogene-b (Cbl-b), a member of the Cbl family of RING finger E3 ubiquitin ligases, has been demonstrated to play a central role in regulating effector T-cell function. Multiple studies using gene-targeting approaches have provided direct evidence that Cbl-b negatively regulates T, B, and NK cell activation via a ubiquitin-mediated protein modulation. Thus, inhibition of Cbl-b ligase activity can lead to immune activation and has therapeutic potential in immuno-oncology.

68 Ga-Pentixafor PET/CT for in-vivo mapping of CXCR4 receptors as potential radiotheranostic targets in soft tissue and bone sarcoma: preliminary results.

Objective: To evaluate the diagnostic utility of 68 Ga-Pentixafor PET/CT for in vivo imaging of CXCR4 receptors in soft tissue/bone sarcoma.

Methods: Ten (7M: 3F; mean age = 24.7 ± 14.

Corrigendum to: Bedaquiline in Drug-Resistant Tuberculosis: A Mini-Review.

In the online version of the article, a change was made in the list of author's and affiliation section. The affiliation of Charan Singh in the online version of the article titled "Bedaquiline in Drug-Resistant Tuberculosis: A Mini-Review" has been updated in "Current Molecular Pharmacology," 2023; 16: e210422203904 [1]. The original article can be found online at: https://www.

Light-Responsive Layer-By-Layer Film Containing Gold Nanorods for Sequential Drug Release.

Chemically and physically stable multidrug-loaded layer-by-layer (LbL) films are promising candidates for sequential and on-demand drug release at concentrations suitable for various applications. The synergistic effect of the sequential release of drugs may enhance their therapeutic efficacy in treating skin cancer and other complex medical conditions. In this study, we prepared LbL films by alternating the deposition of cationic linear polyethylenimine, camptothecin (CPT)-loaded gold nanorods (GNRs), anionic poly(styrenesulfonate), and doxorubicin (DOX) based on electrostatic interactions.

Corrigendum: Identification of novel anti-amoebic pharmacophores from kinase inhibitor chemotypes.

[This corrects the article DOI: 10.3389/fmicb.2023.

Evolutionary insights into 3D genome organization and epigenetic landscape of .

Eukaryotic genomes show an intricate three-dimensional (3D) organization within the nucleus that regulates multiple biological processes including gene expression. Contrary to animals, understanding of 3D genome organization in plants remains at a nascent stage. Here, we investigate the evolution of 3D chromatin architecture in legumes.