Endothelial cell dynamics in sepsis-induced acute lung injury and acute respiratory distress syndrome: pathogenesis and therapeutic implications.

Sepsis, a prevalent critical condition in clinics, continues to be the leading cause of death from infections and a global healthcare issue. Among the organs susceptible to the harmful effects of sepsis, the lungs are notably the most frequently affected. Consequently, patients with sepsis are predisposed to developing acute lung injury (ALI), and in severe cases, acute respiratory distress syndrome (ARDS). Nevertheless, the precise mechanisms associated with the onset of ALI/ARDS remain elusive. In recent years, there has been a growing emphasis on the role of endothelial cells (ECs), a cell type integral to lung barrier function, and their interactions with various stromal cells in sepsis-induced ALI/ARDS. In this comprehensive review, we summarize the involvement of endothelial cells and their intricate interplay with immune cells and stromal cells, including pulmonary epithelial cells and fibroblasts, in the pathogenesis of sepsis-induced ALI/ARDS, with particular emphasis placed on discussing the several pivotal pathways implicated in this process. Furthermore, we discuss the potential therapeutic interventions for modulating the functions of endothelial cells, their interactions with immune cells and stromal cells, and relevant pathways associated with ALI/ARDS to present a potential therapeutic strategy for managing sepsis and sepsis-induced ALI/ARDS.

Inhibition of PPARγ by BZ26, a GW9662 derivate, attenuated obesity-related breast cancer progression by inhibiting the reprogramming of mature adipocytes into to cancer associate adipocyte-like cells.

Obesity has been associated with the development of 13 different types of cancers, including breast cancer. Evidence has indicated that cancer-associated adipocytes promote the proliferation, invasion, and metastasis of cancer. However, the mechanisms that link CAAs to the progression of obesity-related cancer are still unknown. Here, we found the mature adipocytes in the visceral fat of HFD-fed mice have a CAAs phenotype but the stromal vascular fraction of the visceral fat has not. Importantly, we found the derivate of the potent PPARγ antagonist GW9662, BZ26 inhibited the reprogramming of mature adipocytes in the visceral fat of HFD-fed mice into CAA-like cells and inhibited the proliferation and invasion of obesity-related breast cancer. Further study found that it mediated the browning of visceral, subcutaneous and perirenal fat and attenuated inflammation of adipose tissue and metabolic disorders. For the mechanism, we found that BZ26 bound and inhibited PPARγ by acting as a new modulator. Therefore, BZ26 serves as a novel modulator of PPARγ activity, that is, capable of inhibiting obesity-related breast cancer progression by inhibiting of CAA-like cell formation, suggesting that inhibiting the reprogramming of mature adipocytes into CAAs or CAA-like cells may be a potential therapeutic strategy for obesity-related cancer treatment.

The great potential of flavonoids as candidate drugs for NAFLD.

Non-alcoholic fatty liver disease (NAFLD) has a global prevalence of approximately 25 % and is associated with high morbidity and high mortality. NAFLD is a leading cause of cirrhosis and hepatocellular carcinoma. Its pathophysiology is complex and still poorly understood, and there are no drugs used in the clinic to specifically treat NAFLD. Its pathogenesis involves the accumulation of excess lipids in the liver, leading to lipid metabolism disorders and inflammation. Phytochemicals with the potential to prevent or treat excess lipid accumulation have recently received increasing attention, as they are potentially more suitable for long-term use than are traditional therapeutic compounds. In this review, we summarize the classification, biochemical properties, and biological functions of flavonoids and how they are used in the treatment of NAFLD. Highlighting the roles and pharmacological uses of these compounds will be of importance for enhancing the prevention and treatment of NAFLD.

An overview of ferroptosis in non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a public health problem associated with high mortality and high morbidity rates worldwide. Presently, its complex pathophysiology is still unclear, and there is no specific drug to reverse NAFLD. Ferroptosis is an iron-dependent and non-apoptotic form of cell death characterized by the iron-induced accumulation of lipid reactive oxygen species (ROS), which damage nucleic acids, proteins, and lipids; generate intracellular oxidative stress; and ultimately cause cell death. Emerging evidence indicates that ferroptosis is involved in the progression of NAFLD, although the mechanism of action of ferroptosis in NAFLD is still poorly understood. Herein, we summarize the mechanism of action of ferroptosis in certain diseases, especially in the pathogenesis of NAFLD, and discuss the potential therapeutic approaches currently used to treat NAFLD. This review also highlights further directions for the treatment and prevention of NAFLD and related diseases.

The links between gut microbiota and obesity and obesity related diseases.

The obesity epidemic has become a global public health crisis in recent years and is continuing to worsen at an alarming rate. However, the pathophysiological mechanisms involved in the development of obesity and obesity-related diseases are still being unraveled. In the past ten years, the gut microbiota has been identified as a crucial player affecting the onset and progression of obesity and obesity-related diseases, especially with respect to changes in its composition and metabolites during obesity progression. Herein, we summarize the roles and mechanisms of gut microbiota's composition and metabolite changes in the gut play in obesity and obesity related diseases. Furthermore, we discuss potential therapeutic treatments that can be used to modulate the gut microbiome composition and target the relevant metabolic pathways of obesity and obesity-related metabolic diseases.