Liver fibrosis is the convergent point of various liver diseases, such as alcohol consumption, non-alcoholic steatohepatitis (NASH), viral hepatitis, autoimmune hepatitis, and cholestatic liver disease.The common effect of all of these factors on the liver is the generation of a chronic inflammation resulting in an abnormal wound healing response. The generation of a fibrotic response in the liver gives rise to the accumulation of extracellular matrix (ECM) components, leading to fibrous scar formation. The architecture of the liver is disrupted by the presence of a fibrous scar, which causes hepatocyte loss and the deregulation of the normal functioning of the liver, ultimately result......2024-02-26

Tumor surrounding stromal cells, including tumor-associated macrophages (TAMs),crosstalk with the cancer cells to promote oncogenesis, tumor malignant progression, and drug resistance. Esophageal squamous cell carcinoma (ESCC) is among the deadliest types of solid tumors, with the extremely low 5-year overall survival (OS) rate, due to the high recurrence after chemotherapy. Cisplatin is widely used as a standard chemotherapy to treat ESCC patients; however, a plethora of patients suffer from chemoresistance. TAMs-secreted non-cellular substances, such as cytokines, growth factors, or non-coding RNA, function as important factors to provide a permissive microenvironment for tumor growt......2024-02-23

Tumor-associated macrophages (TAMs) are often associated with chemoresistance and resultant poor clinical outcome in solid tumors. Here, we demonstrated that TAMs-released chemokine-C-C motif chemokine 22 (CCL22) in esophageal squamous cell carcinoma (ESCC) stroma was tightly correlated with the chemoresistance of ESCC patients. TAMs-secreted CCL22 was able to block the growth inhibitory and apoptosis promoting effects of cisplatin on ESCC cells. Mechanistically, CCL22 stimulated intratumoral diacylglycerol kinase α (DGKα) to produce phosphatidic acid (PA), which suppressed the activity of NADPH oxidase 4 (NOX4) and then blocked the overproduction of intratumoral reactive species oxy......2024-02-19

The roles of platelets/megakaryocytes (MKs), the key components in the blood system,in the tumor microenvironment and antitumor immunity are unclear. In patients withcolorectal cancer, the number of platelets was significantly increased in patientswith metastasis, and Erbin expression was highly expressed in platelets from patientswith metastases. Moreover, Erbin knockout in platelets/MKs suppressed lung metastasisin mice and promoted aggregations of platelets. Mechanistically, Erbin-deficient plateletshave increasing mitochondrial oxidative phosphorylation and secrete lipid metaboliteslike acyl-carnitine (Acar) by abolishing interaction with prothrombotic protein ESAM.Notably, Acar en......2024-02-18

For decades the common dogma was that the adult heart is incapable of regenerating lost myocardium after injury. In response to cardiac injury, adult mammals—including humans—fail to regenerate the majority of the lost cardiomyocytes and instead replace necrotic muscle with scar tissue. The loss of cardiomyocytes eventually compromises contractility of the remaining myocardium, leading to heart failure and death when the extent of injury is severe.Achieving cardiac regeneration or stimulating endogenous repair mechanisms to restore cardiac function after injury has been a goal of countless investigators. In the last decade scientists have questioned whether the mature heart truly l......2024-02-18

When one hears the word “vaccine,” many people think of vaccines against infectious agents, such as viruses and bacteria.The idea of vaccination against cancer has a long history and was initially built on the observation that some tumors spontaneously regress in patients experiencing an acute infection. How a non-specific innate immune response against bacterial products could translate into a specific anti-tumor immune response was explained subsequently by the discovery that dendritic cells (DCs) could acquire immunogenic tumor-derived peptides released during the innate immune response. This led to the hypothesis that use of tumor-derived antigens, if delivered to the immune sy......2024-01-19