Heat shock proteins as hallmarks of cancer: insights from molecular mechanisms to therapeutic strategies.

Heat shock proteins are essential molecular chaperones that play crucial roles in stabilizing protein structures, facilitating the repair or degradation of damaged proteins, and maintaining proteostasis and cellular functions. Extensive research has demonstrated that heat shock proteins are highly expressed in cancers and closely associated with tumorigenesis and progression. The "Hallmarks of Cancer" are the core features of cancer biology that collectively define a series of functional characteristics acquired by cells as they transition from a normal state to a state of tumor growth, including sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, enabled replicative immortality, the induction of angiogenesis, and the activation of invasion and metastasis.

Assembly of spirocyclic pyrazolone-pyrrolo[4,3,2-]quinoline skeleton cascade [1,5] hydride transfer/cyclization by C(sp)-H functionalization.

Herein, a highly efficient, scalable, and cascade [1,5] hydride transfer/cyclization method for constructing unique spirocyclic pyrazolone-pyrrolo[4,3,2-]quinoline structures C(sp)-H functionalization is achieved, using pyrazolones and oxindoles attached to C4 amines. This strategy represents a limited approach utilizing C-H activation to construct spirocyclic pyrazolone scaffolds with moderate to excellent reaction performance.

Gut microbiota: A magical multifunctional target regulated by medicine food homology species.

Background: The relationship between gut microbiota and human health has gradually been recognized. Increasing studies show that the disorder of gut microbiota is related to the occurrence and development of many diseases. Metabolites produced by the gut microbiota are responsible for their extensive regulatory roles.

Recent Advances on Direct Functionalization of Indoles in Aqueous Media.

Indoles and their derivatives have dominated a significant proportion of nitrogen-containing heterocyclic compounds and play an essential role in synthetic and medicinal chemistry, pesticides, and advanced materials. Compared with conventional synthetic strategies, direct functionalization of indoles provides straightforward access to construct diverse indole scaffolds. As we enter an era emphasizing green and sustainable chemistry, utilizing environment-friendly solvents represented by water demonstrates great potential in synthesizing valuable indole derivatives.

Application of Novel Degraders Employing Autophagy for Expediting Medicinal Research.

Targeted protein degradation (TPD) technology is based on a unique pharmacological mechanism that has profoundly revolutionized medicinal research by overcoming limitations associated with traditional small-molecule drugs. Autophagy, a mechanism for intracellular waste disposal and recovery, is an important biological process in medicinal research. Recently, studies have demonstrated that several emerging autophagic degraders can treat human diseases.

The emerging role of radical chemistry in the amination transformation of highly strained [1.1.1]propellane: Bicyclo[1.1.1]pentylamine as bioisosteres of anilines.

Bicyclo[1.1.1]pentylamines (BPCAs), emerging as sp-rich surrogates for aniline and its derivatives, demonstrate unique structural features and physicochemical profiles in medicinal and synthetic chemistry.

Construction of Oxo-Bridged Diazocines via Rhodium-Catalyzed (4+3) Cycloaddition of Carbonyl Ylides with Azoalkenes.

Developing efficient strategies for synthesizing novel diazocine compounds is valuable because their use has been limited by their synthetic accessibility. This work describes the catalytic (4+3) cycloaddition reaction of carbonyl ylides with azoalkenes generated . The rhodium-catalyzed cascade reaction features good atom and step economy, providing the first access to oxo-bridged diazocines.

CML/RAGE Signal Bridges a Common Pathogenesis Between Atherosclerosis and Non-alcoholic Fatty Liver.

Non-alcoholic fatty liver disease (NAFLD) has become a common chronic disease in the world. NAFLD is not only a simple intrahepatic lesion, but also affects the occurrence of a variety of extrahepatic complications. In particular, cardiovascular complications are particularly serious, which is the main cause of death in patients with NAFLD.

Advanced Glycation End Products Induce Vascular Smooth Muscle Cell-Derived Foam Cell Formation and Transdifferentiate to a Macrophage-Like State.

Background: Advanced glycation end products play an important role in diabetic atherosclerosis. The effects of advanced glycation end products (AGEs) on vascular smooth muscle cell- (VSMC-) derived foam cell formation and phenotypic transformation are unknown.

Methods: Serological and histological samples were obtained from diabetic amputation patients and accident amputation patients from the Affiliated Hospital of Jiangsu University.

Macrophage galectin-3 enhances intimal translocation of vascular calcification in diabetes mellitus.

The clinical risks and prognosis of diabetic vascular intimal calcification (VIC) and medial calcification (VMC) are different. This study aims to investigate the mechanism of VIC/VMC translocation. Anterior tibial arteries were collected from patients with diabetic foot amputation.

N-Carboxymethyl-Lysine Negatively Regulates Foam Cell Migration via the Vav1/Rac1 Pathway.

Background: Macrophage-derived foam cells play a central role in atherosclerosis, and their ultimate fate includes apoptosis, promotion of vascular inflammation, or migration to other tissues. N-Carboxymethyl-lysine (CML), the key active component of advanced glycation end products, induced foam cell formation and apoptosis. Previous studies have shown that the Vav1/Rac1 pathway affects the macrophage cytoskeleton and cell migration, but its role in the pathogenesis of diabetic atherosclerosis is unknown.

Role of Matrix Vesicles in Bone-Vascular Cross-Talk.

Matrix mineralization can be divided into physiological mineralization and pathological mineralization. There is a consensus among existing studies that matrix vesicles (MVs) are the starting sites of bone mineralization, and each component of MVs serves a certain function in mineralization. In addition, ectopic MVs pathologically promote undesired calcification, the primary focus of which is the promotion of vascular calcification.

Mechanisms of Matrix Vesicles Mediating Calcification Transition in Diabetic Plaque.

Vascular calcification is a key character of advanced plaque in diabetic atherosclerosis. Microcalcification induces plaque rupture, whereas macrocalcification contributes to plaque stability. However, there is still no clear explanation for the formation and transition of these two types of calcification.

RAGE/galectin-3 yields intraplaque calcification transformation via sortilin.

Aims: Macrocalcification and microcalcification present different clinical risks, but the regulatory of their formation was unclear. Therefore, this study explored the underlying mechanisms of macrocalcification and microcalcification in diabetes mellitus.

Methods: Anterior tibial arteries of amputated diabetic feet were collected.

Role of AGEs in the progression and regression of atherosclerotic plaques.

The formation of advanced glycation end-products(AGEs) is an important cause of metabolic memory in diabetic patients and a key factor in the formation of atherosclerosis(AS) plaques in patients with diabetes mellitus. Related studies showed that AGEs could disrupt hemodynamic steady-state and destroy vascular wall integrity through the endothelial barrier damage, foam cell(FC) formation, apoptosis, calcium deposition and other aspects. At the same time, AGEs could initiate oxidative stress and inflammatory response cascade via receptor-depended and non-receptor-dependent pathways, promoting plaques to develop from a steady state to a vulnerable state and eventually tend to rupture and thrombosis.