Nuclear and Molecular Medicine

Mutations in the human PURA gene cause the neurodevelopmental PURA syndrome. In contrast to several other monogenetic disorders, almost all reported mutations in this nucleic acid-binding protein result in the full disease penetrance. In this study, we observed that patient mutations across PURA impair its previously reported co-localization with processing bodies. These mutations either destroyed the folding integrity, RNA binding, or dimerization of PURA. We also solved the crystal structures of the N- and C-terminal PUR domains of human PURA and combined them with molecular dynamics simulations and nuclear magnetic resonance measurements...

Acute myelogenous leukaemia (AML) originates and is maintained by leukaemic stem cells (LSCs) that are inherently resistant to antiproliferative therapies, indicating that a critical strategy for overcoming chemoresistance in AML therapy is to eradicate LSCs. In this work, we investigated the anti-AML activity of bortezomib (BTZ), emphasizing its anti-LSC potential, using KG-1a cells, an AML cell line with stem-like properties. BTZ presented potent cytotoxicity to both solid and haematological malignancy cells and reduced the stem-like features of KG-1a cells, as observed by the reduction in CD34- and CD123-positive cells...

The evolving landscape of personalized medicine necessitates a shift from traditional therapeutic interventions towards precision-driven approaches. Embracing this paradigm, our research probes the therapeutic efficacy of the aqueous crude extract (ACE) of Calocybe indica in cervical cancer treatment, merging botanical insights with advanced molecular research. We observed that ACE exerts significant influences on nuclear morphology and cell cycle modulation, further inducing early apoptosis and showcasing prebiotic attributes...

Lymphoid restricted membrane protein (LRMP) is a specific regulator of the hyperpolarization-activated cyclic nucleotide-sensitive isoform 4 (HCN4) channel. LRMP prevents cAMP-dependent potentiation of HCN4, but the interaction domains, mechanisms of action, and basis for isoform-specificity remain unknown. Here, we identify the domains of LRMP essential for this regulation, show that LRMP acts by disrupting the intramolecular signal transduction between cyclic nucleotide binding and gating, and demonstrate that multiple unique regions in HCN4 are required for LRMP isoform-specificity...

The incidence of inflammatory bowel disease (IBD) and the associated risk of colon cancer are increasing globally. Traditional Chinese medicine (TCM) treatment has unique advantages. The Sishen Pill, a common Chinese patented drug used to treat abdominal pain and diarrhea, consists mainly of Psoraleae Fructus, Myristicae Semen, Euodiae Fructus, and Schisandra Chinensis. Modern research has confirmed that Sishen Pill and its active secondary metabolites, such as psoralen, myristicin, evodiamine, and schisandrin, can improve intestinal inflammation and exert antitumor pharmacological effects...

No abstract text is available yet for this article.

Knee osteoarthritis (KOA) is a prevalent degenerative joint disease that is primarily managed by improving the destroyed cartilage and reversing subchondral bone remodeling. Total glucosides of white paeony (TGP) capsule primarily contains extracts from the white peony root and has been shown to have various pharmacological effects, but its role in KOA still requires comprehensive evaluation. In this study, we aimed to investigate the protective effect of TGP on knee cartilage and subchondral bone, as well as elucidate the underlying molecular mechanisms...

The fundamental interest in actinide chemistry, particularly for the development of thorium-based materials, is experiencing a renaissance owing to the recent and rapidly growing attention to fuel cycle reactors, radiological daughters for nuclear medicine, and efficient nuclear stockpile development. Herein, we uncover fundamental principles of thorium chemistry on the example of Th-based extended structures such as metal-organic frameworks in comparison with the discrete systems and zirconium extended analogs, demonstrating remarkable over two-and-half-year chemical stability of Th-based frameworks as a function of metal node connectivity, amount of defects, and conformational linker rigidity through comprehensive spectroscopic and crystallographic analysis as well as theoretical modeling...

PURPOSE: One of the main reasons for prostate cancer (PCa) recurrence is the difficulty in identifying and removing cancerous lesions during surgery. Accurately localizing and excising cancerous tissue remains a significant challenge. The second near-infrared window (NIR-II, 1000-1700 nm) fluorescence offers enhanced resolution, a high signal-to-noise ratio, and the potential for deeper tissue penetration. However, this technology is not currently employed for intraoperative imaging of PCa...

NKAP mutations are associated with Hackmann-Di Donato-type X-linked syndromic intellectual developmental disorder (MRXSHD, MIM: #301039). Here, we elucidate the potential prenatal manifestation of NKAP mutation-associated disorder for the first time, alongside revealing the relationship between NKAP mutations and congenital heart defect (CHD) in the Chinese population. An NKAP mutation (NM_024528.4: c.988C>T, p.Arg330Cys) was identified in two foetuses presenting with CHD. Subsequent mechanistic exploration revealed a marked downregulation of NKAP transcription within HEK293T cells transfected with NKAP p...

Radiolabeling of biomolecules and cells with radiolabeled prosthetic groups has significant implications for nuclear medicine, imaging, and radiotherapy. Achieving site-specific and controlled incorporation of radiolabeled prostheses under mild reaction conditions is crucial for minimizing the impact on the bioactivity of the radiolabeled compounds. The targeting of natural and abundant amino acids during radiolabeling of biomolecules often results in nonspecific and uncontrolled modifications. Cysteine is distinguished by its low natural abundance and unique nucleophilicity...

The field of theranostics is rapidly advancing, driven by the goals of enhancing patient care. Recent breakthroughs in artificial intelligence (AI) and its innovative theranostic applications have marked a critical step forward in nuclear medicine, leading to a significant paradigm shift in precision oncology. For instance, AI-assisted tumor characterization, including automated image interpretation, tumor segmentation, feature identification, and prediction of high-risk lesions, improves diagnostic processes, offering a precise and detailed evaluation...

BACKGROUND: Spinal cord injury (SCI)-induced neuroinflammation and oxidative stress (OS) are crucial events causing neurological dysfunction. Aconitate decarboxylase 1 (ACOD1) and its metabolite itaconate (Ita) inhibit inflammation and OS by promoting alkylation of Keap1 to induce Nrf2 expression; however, it is unclear whether there is another pathway regulating their effects in inflammation-activated microglia after SCI. METHODS: Adult male C57BL/6 ACOD1-/-  mice and their wild-type (WT) littermates were subjected to a moderate thoracic spinal cord contusion...

INTRODUCTION: Bacterial infections are a major problem in medicine, and the rapid and accurate detection of such infections is essential for optimal patient outcome. Bacterial infections can be diagnosed by nuclear imaging, but most currently available modalities are unable to discriminate infection from sterile inflammation. Bacteria-targeted positron emission tomography (PET) tracers have the potential to overcome this hurdle. In the present study, we compared three 18 F-labelled PET tracers based on the clinically applied antibiotic vancomycin for targeted imaging of Gram-positive bacteria...

Osteoarthritis (OA) is a complicated joint disorder characterized by inflammation that causes joint destruction. Cucurbitacin B (CuB) is a naturally occurring triterpenoid compound derived from plants in the Cucurbitaceae family. The aim of this study is to investigate the potential role and mechanisms of CuB in a mouse model of OA. This study identified the key targets and potential pathways of CuB through network pharmacology analysis. In vivo and in vitro studies confirmed the potential mechanisms of CuB in OA...

UNLABELLED: Alpha-particle radionuclide-antibody conjugates are being clinically evaluated against solid tumors even when they moderately express the targeted markers. At this limit of lower tumor-absorbed doses, to maintain efficacy, the few(er) intratumorally delivered alpha-particles need to traverse/hit as many different cancer cells as possible. We complement antibody-radioconjugate therapies with a separate nanocarrier delivering a fraction of the same total injected radioactivity to tumor regions geographically different than those affected by targeting antibodies; these carrier-cocktails collectively distribute the alpha-particle emitters better...

BACKGROUND: Doxorubicin (DOX) is an effective anticancer agent. However, the clinical outcomes of DOX-based therapies are severely hampered by their significant cardiotoxicity. PURPOSE: We investigated the beneficial effects of an ethanol extract of Cirsium setidens (CSE) on DOX-induced cardiomyotoxicity (DICT). METHODS: UPLC-TQ/MS analysis was used to identify CSE metabolite profiles. H9c2 rat cardiomyocytes and MDA-MB-231 human breast cancer cells were used to evaluate the effects of CSE on DICT-induced cell death...

BACKGROUND: The utilization of Chinese medicine as an adjunctive therapy for cancer has recently gained significant attention. Ferroptosis, a newly regulated cell death process depending on the ferrous ions, has been proved to be participated in glioma stem cells inactivation. PURPOSE: We aim to study whether ginsenoside Rg5 exerted inhibitory effects on crucial aspects of glioma stem cells, including cell viability, tumor initiation, invasion, self-renewal ability, neurosphere formation, and stemness...

BACKGROUND: Oxidative stress can lead to uncontrolled glucose metabolism and, thus, diabetes. Auricularia auricula-judae (Bull.) Quél. polysaccharides possess biological activities, such as antioxidant and hypoglycemic effects, but their mechanism of their acid hydrolysates on oxidative stress-injured glucose metabolism disorders is unclear. PURPOSE: Using diabetic mice, we investigated the effect of the acid hydrolysate of polysaccharides from Auricularia auricula-judae (Bull...

Macrophage‑inducible C‑type lectin receptor (Mincle) is predominantly found on antigen‑presenting cells. It can recognize specific ligands when stimulated by certain pathogens such as fungi and Mycobacterium tuberculosis . This recognition triggers the activation of the nuclear factor‑κB pathway, leading to the production of inflammatory factors and contributing to the innate immune response of the host. Moreover, Mincle identifies lipid damage‑related molecules discharged by injured cells, such as Sin3‑associated protein 130, which triggers aseptic inflammation and ultimately hastens the advancement of renal damage, autoimmune disorders and malignancies by fostering tissue inflammation...