Berberine on the Prevention and Management of Cardiometabolic Disease: Clinical Applications and Mechanisms of Action.

Berberine is an alkaloid from several medicinal plants originally used to treat diarrhea and dysentery as a traditional Chinese herbal medicine. In recent years, berberine has been discovered to exhibit a wide spectrum of biological activities in the treatment of diverse diseases ranging from cancer and neurological dysfunctions to metabolic disorders and heart diseases. This review article summarizes the clinical practice and laboratory exploration of berberine for the treatment of cardiometabolic and heart diseases, with a focus on the novel insights and recent advances of the underlying mechanisms recognized in the past decade. Berberine was found to display pleiotropic therapeutic effects against dyslipidemia, hyperglycemia, hypertension, arrhythmia, and heart failure. The mechanisms of berberine for the treatment of cardiometabolic disease involve combating inflammation and oxidative stress such as inhibiting proprotein convertase subtilisin/kexin 9 (PCSK9) activation, regulating electrical signals and ionic channels such as targeting human ether-a-go-go related gene (hERG) currents, promoting energy metabolism such as activating adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, modifying gut microbiota to promote transforming of berberine into its intestine-absorbable form, and interacting with non-coding RNAs via targeting multiple signaling pathways such as AMPK, mechanistic target of rapamycin (mTOR), etc. Collectively, berberine appears to be safe and well-tolerated in clinical practice, especially for those who are intolerant to statins. Knowledge from this field may pave the way for future development of more effective pharmaceutical approaches for managing cardiometabolic risk factors and preventing heart diseases.

Muscle Atrophy in Cancer.

Cancer is a prevalent disease with high mortality and morbidity. Muscle atrophy is a severe and disabling clinical condition that frequently accompanies cancer development such as muscle atrophy in pancreatic cancer, lung cancer, and bladder cancer. The majority of cancer patients are accompanied with cachexia. Cancer-associated cachexia is characterized by weight loss and muscle atrophy. Muscle wasting is a pivotal feature of cancer cachexia. Muscle atrophy refers to the reduction of muscle mass caused by muscle itself or the dysfunction of nervous system. Muscle atrophy causes serious clinical consequences such as physical impairment, poor life quality, reduced tolerance to treatments, and short survival. Although many reports have studied cancer-related muscle atrophy, there is still no clear understanding of it. Here we will describe the prevalence, mechanisms, pathophysiological effects, and current clinical treatments of muscle atrophy in cancer.

Muscle Atrophy: Present and Future.

Muscle atrophy is the loss of muscle mass and strength, and it occurs in many diseases, such as cancer, AIDS (acquired immunodeficiency syndrome), congestive heart failure, COPD (chronic obstructive pulmonary disease), renal failure, and severe burns. Muscle atrophy accompanied by cachexia worsens patient's life quality and increases morbidity and mortality. To date there is no effective treatment on that. Here we summarize the diagnosis methods and cellular mechanisms of muscle atrophy. We also discuss the current strategies in muscle atrophy treatment and highlight the potential treatment strategies to resist muscle atrophy.

The Role of Circular RNAs in Cerebral Ischemic Diseases: Ischemic Stroke and Cerebral Ischemia/Reperfusion Injury.

Cerebral ischemic diseases including ischemic stroke and cerebral ischemia reperfusion injury can result in serious dysfunction of the brain, which leads to extremely high mortality and disability. There are no effective therapeutics for cerebral ischemic diseases to date. Circular RNAs are a kind of newly investigated noncoding RNAs. It is reported that circular RNAs are enriched in multiple organs, especially abundant in the brain, which indicates that circular RNAs may be involved in cerebral physiological and pathological processes. In this chapter, we will firstly review the pathophysiology, underlying mechanisms, and current treatments of cerebral ischemic diseases including ischemic stroke and cerebral ischemia/reperfusion injury. Secondly, the characteristics and function of circular RNAs will be outlined, and then we are going to introduce the roles circular RNAs play in human diseases. Finally, we will summarize the function of circular RNAs in cerebral ischemic diseases.

Functional Role of Circular RNA in Regenerative Medicine.

Every year, millions of people around the world suffer from different forms of tissue trauma. Regenerative medicine refers to therapy that replaces the injured organ or cells. Stem cells are the frontiers and hotspots of current regenerative medicine research. Circular RNAs (circRNAs) are essential for the early development of many species. It was found that they could guide stem cell differentiation through interacting with certain microRNAs (miRNAs). Based on this concept, it is meaningful to look into how circRNAs influence stem cells and its role in regenerative medicine. In this chapter we will discuss the functional roles of circRNAs in the prevention, repair, or progression of chronic diseases, through the communication between stem cells.

The Emerging Role of MicroRNA-155 in Cardiovascular Diseases.

MicroRNAs have been demonstrated to be involved in human diseases, including cardiovascular diseases. Growing evidences suggest that microRNA-155, a typical multifunctional microRNA, plays a crucial role in hematopoietic lineage differentiation, immunity, inflammation, viral infections, and vascular remodeling, which is linked to cardiovascular diseases such as coronary artery disease, abdominal aortic aneurysm, heart failure, and diabetic heart disease. The effects of microRNA-155 in different cell types through different target genes result in different mechanisms in diseases. MicroRNA-155 has been intensively studied in atherosclerosis and coronary artery disease. Contradictory results of microRNA-155 either promoting or preventing the pathophysiological process of atherosclerosis illustrate the complexity of this pleiotropic molecule. Therefore, more comprehensive studies of the underlying mechanisms of microRNA-155 involvement in cardiovascular diseases are required. Furthermore, a recent clinical trial of Miravirsen targeting microRNA-122 sheds light on exploiting microRNA-155 as a novel target to develop effective therapeutic strategies for cardiovascular diseases in the near future.

Prostaglandin receptor EP4 in abdominal aortic aneurysms.

Abdominal aortic aneurysm (AAA) pathogenesis is distinguished by vessel wall inflammation. Cyclooxygenase (COX)-2 and microsomal prostaglandin E synthase-1, key components of the most well-characterized inflammatory prostaglandin pathway, contribute to AAA development in the 28-day angiotensin II infusion model in mice. In this study, we used this model to examine the role of the prostaglandin E receptor subtype 4 (EP4) and genetic knockdown of COX-2 expression (70% to 90%) in AAA pathogenesis. The administration of the prostaglandin receptor EP4 antagonist AE3-208 (10 mg/kg per day) to apolipoprotein E (apoE)-deficient mice led to active drug plasma concentrations and reduced AAA incidence and severity compared with control apoE-deficient mice (P < 0.01), whereas COX-2 genetic knockdown/apoE-deficient mice displayed only a minor, nonsignificant decrease in incidence of AAA. EP4 receptor protein was present in human and mouse AAA, as observed by using Western blot analysis. Aortas from AE3-208-treated mice displayed evidence of a reduced inflammatory phenotype compared with controls. Atherosclerotic lesion size at the aortic root was similar between all groups. In conclusion, the prostaglandin E(2)-EP4 signaling pathway plays a role in the AAA inflammatory process. Blocking the EP4 receptor pharmacologically reduces both the incidence and severity of AAA in the angiotensin II mouse model, potentially via attenuation of cytokine/chemokine synthesis and the reduction of matrix metalloproteinase activities.