F-FDG PET/CT metabolic parameters are correlated with clinical features and valuable in clinical stratification management in patients of castleman disease.

Background: Castleman disease (CD) is a rare lymphoproliferative disorder. This study is to evaluate the correlation between F-flurodeoxyglucose (F-FDG) positron emission tomography-computed tomography (PET/CT) and clinical features in CD patients, and exploring its value in distinguishing disease severity and assisting in risk stratification.

Methods: We retrospectively enrolled 93 patients with newly diagnosed CD.

Elevated protein lactylation promotes immunosuppressive microenvironment and therapeutic resistance in pancreatic ductal adenocarcinoma.

Metabolic reprogramming shapes tumor microenvironment (TME) and may lead to immunotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Elucidating the impact of pancreatic cancer cell metabolism in the TME is essential to therapeutic interventions. "Immune cold" PDAC is characterized by elevated lactate levels resulting from tumor cell metabolism, abundance of pro-tumor macrophages, and reduced cytotoxic T cell in the TME.

Microneedle-Array-Mediated Transdermal Delivery of GCV-Functionalized Zeolitic Imidazolate Framework-8 Nanoparticles for KSHV Treatment.

Kaposi's sarcoma-associated herpesvirus (KSHV) is a variety of the human gamma-herpesvirus that often leads to the occurrence of malignant tumors. In addition, the occurrence of Kaposi's sarcoma is a major cause of death among AIDS patients. Ganciclovir (GCV) is the most widely used drug against KSHV infection in the clinic.

A continuously efficient O-supplying strategy for long-term modulation of hypoxic tumor microenvironment to enhance long-acting radionuclides internal therapy.

Radionuclides internal radiotherapy (RIT) is a clinically powerful method for cancer treatment, but still poses unsatisfactory therapeutic outcomes due to the hypoxic characteristic of tumor microenvironment (TME). Catalase (CAT) or CAT-like nanomaterials can be used to enzymatically decompose TME endogenous HO to boost TME oxygenation and thus alleviate the hypoxic level within tumors, but their effectiveness is still hindered by the short-lasting of hypoxia relief owing to their poor stability or degradability, thereby failing to match the long therapeutic duration of RIT. Herein, we proposed an innovative strategy of using facet-dependent CAT-like Pd-based two-dimensional (2D) nanoplatforms to continuously enhance RIT.

Puromycin Prodrug Activation by Thioredoxin Reductase Overcomes Its Promiscuous Cytotoxicity.

Overexpression of the selenoprotein thioredoxin reductase (TrxR) has been documented in malignant tissues and is of pathological significance for many types of tumors. The antibiotic puromycin (Puro) is a protein synthesis inhibitor causing premature polypeptide chain termination during translation. The well-defined action mechanism of Puro makes it a useful tool in biomedical studies.

Revealing PACMA 31 as a new chemical type TrxR inhibitor to promote cancer cell apoptosis.

Thioredoxin reductase (TrxR) is a pivotal regulator of redox homeostasis, while dysregulation of redox homeostasis is a hallmark for cancer cells. Thus, there is considerable potential to inhibit the aberrantly upregulated TrxR in cancer cells to discover selective cancer therapeutic agents. Nevertheless, the structural types of TrxR inhibitors presented currently are still relatively limited.

Novel strategies for targeting the thioredoxin system for cancer therapy.

Introduction: The thioredoxin system is increasingly recognized as an important executor for maintaining cell redox homeostasis and regulating multiple cell signaling pathways. Targeting this system for cancer treatment has therefore attracted much attention.

Areas Covered: The authors focus on providing coverage and emphasizing the strategy of targeting the thioredoxin system to develop anticancer therapeutics in the past five years, especially from the perspective of discovering novel protein functions or new downstream regulatory pathways, and designing new therapeutic reagents.

Inhibition of thioredoxin reductase by natural anticancer candidate β-lapachone accounts for triggering redox activation-mediated HL-60 cell apoptosis.

β-Lapachone as a natural novel anticancer candidate is under clinical trials. Previous studies suggested that β-lapachone works by redox activation to ablate cancer cells. However, it is still unclear whether thioredoxin reductase (TrxR), one of the key redox catalytic enzymes in cells, plays a role in the pharmacological effects of β-lapachone.

Integration of a Diselenide Unit Generates Fluorogenic Camptothecin Prodrugs with Improved Cytotoxicity to Cancer Cells.

A diselenide/disulfide unit was introduced into camptothecin (CPT), and two selenoprodrugs (e.g., CPT-Se3 and CPT-Se4) were identified to show improved potency in killing cancer cells and inhibiting tumor growth .

Structural Modification of Aminophenylarsenoxides Generates Candidates for Leukemia Treatment Thioredoxin Reductase Inhibition.

Upregulation of the selenoprotein thioredoxin reductase (TrxR) is of pathological significance in maintaining tumor phenotypes. Thus, TrxR inhibitors are promising cancer therapeutic agents. We prepared different amino-substituted phenylarsine oxides and evaluated their cytotoxicity and inhibition of TrxR.

Inhibition of Thioredoxin Reductase by Santamarine Conferring Anticancer Effect in HeLa Cells.

Natural products frequently have unique physiological activities and new action mechanisms due to their structural diversity and novelty, and are an important source for innovative drugs and lead compounds. We present herein that natural product santamarine targeted thioredoxin reductase (TrxR) to weaken its antioxidative function in cells, accompanied by accumulation of high levels of reactive oxygen species (ROS), and finally induced a new mechanism of tumor cell oxidative stress-mediated apoptosis. TrxR knockdown or overexpression cell lines were employed to further evaluate the cytotoxicity of santamarine regulated by TrxR, demonstrated that TrxR played a key role in the physiological effect of santamarine on cells.

Indole Alkaloids from a Soil-Derived .

Clonorosins A () and B (), two novel indole alkaloids featuring unprecedented 6/5/6/6/5 and 6/5/5 cores, together with seven known indole-linked 2,5-diketopiperazine alkaloids (-), were isolated from the soil-derived fungus YRS-06. The new structures were proposed through HR-MS, NMR, and ECD spectroscopic data. They were established by comparing the calculated NMR, ECD, and specific rotation data with the experimental.

Onopordopicrin from the new genus as a novel thioredoxin reductase inhibitor to induce oxidative stress-mediated tumor cell apoptosis.

Isolation and identification of natural products from plants is an essential approach for discovering drug candidates. Herein we report the characterization of three sesquiterpene lactones from a new genus , e.g.

Xanthohumol Analogues as Potent Nrf2 Activators against Oxidative Stress Mediated Damages of PC12 Cells.

The nuclear factor erythroid 2-related factor 2 (Nrf2), a master transcription factor controlling a series of cytoprotective genes, is closely associated with scavenging the reactive oxygen species and maintaining the intracellular redox balance. Accumulating evidence has indicated that activation of Nrf2 is efficient to block or retard oxidative stress mediated neurodegenerative disorders. Small molecules that contribute directly or indirectly to the Nrf2 activation thus are promising therapeutic agents.

(±)-Alternamgin, a Pair of Enantiomeric Polyketides, from the Endophytic Fungi Alternaria sp. MG1.

A pair of enantiomeric polyketides, (+)- and (-)-alternamgin (1), featuring an unprecedented 6/6/6/6/5/6/6 seven ring backbone, were isolated from the endophytic fungi Alternaria sp. MG1. The relative configuration of 1 was determined using X-ray diffraction, and the absolute configurations of (±)-1 were confirmed by comparing the experimental and calculated ECD data.