Development and evaluation of albumin binder-conjugated heterodimeric radiopharmaceuticals targeting integrin αβ and CD13 for cancer therapy.

Purpose: The advancement of heterodimeric tracers, renowned for their high sensitivity, marks a significant trend in the development of radiotracers for cancer diagnosis. Our prior work on [Ga]Ga-HX01, a heterodimeric tracer targeting CD13 and integrin αβ, led to its approval for phase I clinical trials by the China National Medical Production Administration (NMPA). However, its fast clearance and limited tumor retention pose challenges for broader clinical application in cancer treatment.

Discovery of a pyrano[2,3-b]pyridine derivative YX-2102 as a cannabinoid receptor 2 agonist for alleviating lung fibrosis.

Background: Pharmacological modulation of cannabinoid 2 receptor (CB2R) is a promising therapeutic strategy for pulmonary fibrosis (PF). Thus, to develop CB2R selective ligands with new chemical space has attracted much research interests. This work aims to discover a novel CB2R agonist from an in-house library, and to evaluate its therapeutic effects on PF model, as well as to disclose the pharmacological mechanism.

Discovery of Novel Autophagy Inhibitors and Their Sensitization Abilities for Vincristine-Resistant Esophageal Cancer Cell Line Eca109/VCR.

Resistance phenomena, especially acquired drug resistance, have been severely hampering the application of chemotherapeutics during cancer chemotherapy. Autophagy plays a role in maintaining the survival of cancer cells and might mediate resistance to chemotherapy drugs. Herein, a new series of 5-amino-2-ether-benzamide derivatives were synthesized and evaluated as autophagy inhibitors.

CircMRPS35 suppresses gastric cancer progression via recruiting KAT7 to govern histone modification.

Background: Aberrant expression of circular RNAs contributes to the initiation and progression of cancers, but the underlying mechanism remains elusive.

Methods: RNA-seq and qRT-PCR were performed to screen differential expressed circRNAs between gastric cancer tissues and adjacent normal tissues. Candidate circRNA (circMRPS35) was screened out and validated by qRT-PCR.

Characterizing the Binding Sites for GK Domain of DLG1 and DLG4 via Molecular Dynamics Simulation.

Discs-large (DLG) is a member that belongs to the membrane-associated guanylate kinase (MAGUK) family. The GK domain of DLGs has evolved into a protein-protein interaction module that could bind with kinds of proteins to regulate diverse cellular functions. Previous reports have demonstrated the GK domain of DLGs functioned as a phosphor-peptide-binding module by resolving the crystal structures.

Simvastatin alleviated diabetes mellitus-induced erectile dysfunction in rats by enhancing AMPK pathway-induced autophagy.

Background: Diabetes mellitus-induced erectile dysfunction is a common diabetic complication, and new therapeutics and the pathogenesis of diabetes mellitus-induced erectile dysfunction need to be investigated.

Objectives: The aim was to investigate the pathogenesis of diabetes mellitus-induced erectile dysfunction and the pharmacological mechanism of simvastatin treatment in diabetes mellitus-induced erectile dysfunction model rats.

Materials And Methods: A total of 86 male Sprague Dawley rats aged 8 weeks old were used in this study.

2,3-Dicyano-5,6-dichlorobenzoquinone-Mediated and Selective C-O and C-C Cross-Couplings of Phenols and Porphyrins.

A selective C-O cross-coupling reaction between porphyrins and phenols has been developed through 2,3-dicyano-5,6-dichlorobenzoquinone (DDQ)/Sc(OTf) oxidation, efficiently delivering -etherified porphyrins in good yields (≤93%). The radical complex process was proposed and calculated as the rationalized mechanism to block the homocoupling process. In addition, the switchable selective C-C cross-coupling reaction was achieved by using bulky electron-rich phenols and naphthols under DDQ oxidation conditions.

Binding interactions of epididymal protease inhibitor and semenogelin-1: a homology modeling, docking and molecular dynamics simulation study.

Epididymal protease inhibitor (EPPIN) that is located on the sperm surface and specific to the male reproductive system is a non-hormonal contraceptive target, since the binding of EPPIN with the seminal plasma protein semenogelin-1 (SEMG1) causes a loss of sperm function. Here, we investigated the binding interactions between EPPIN and SEMG1 by homology modeling, docking and molecular dynamics simulation. Since no crystal structure was reported for EPPIN, its 3D structure was constructed by homology modeling and refined by dynamics simulation, illustrating the C-terminus domain of EPPIN could bind with its N-terminus domain through the residues 30-32 and 113-116.

[4 + 1 + 1] Annulations of α-Bromo Carbonyls and 1-Azadienes toward Fused Benzoazaheterocycles.

An unexpected [4 + 1 + 1] annulation between α-bromo carbonyls and 1-azadienes, derived from 2-methylenebenzofuran-3(2 H)-ones or 2-methylenebenzo[ b]thiophene-3(2 H)-ones, has been observed in the presence of DABCO and CsCO. These reactions stand in contrast to the common [4 + 1] cyclization reactions of azadienes with the related sulfonium ylides. A range of fused benzofuro[3,2- b]pyridines and benzo[4,5]thieno[3,2- b]pyridines have been efficiently constructed in fair to excellent yields.

Tanshinone IIA inhibits HIF-1α and VEGF expression in breast cancer cells via mTOR/p70S6K/RPS6/4E-BP1 signaling pathway.

Hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) play important roles in angiogenesis and tumor growth. Tanshinone IIA (T2A) is a novel antiangiogenic agent with promising antitumor effects; however, the molecular mechanism underlying the antiangiogenic effects of T2A remains unclear. In the present study, we provided evidence showing that T2A inhibited angiogenesis and breast cancer growth by down-regulating VEGF expression.

Mitochondrial translocation of cofilin is required for allyl isothiocyanate-mediated cell death via ROCK1/PTEN/PI3K signaling pathway.

Background: Cofilin is a member of the actin depolymerizing factor (ADF)/cofilin family, which regulates actin dynamics. Increasing evidence suggests that mitochondrial translocation of cofilin appears necessary for the regulation of apoptosis.

Results: We report that allyl isothiocyanate (AITC) potently induces mitochondria injury and apoptosis.