Dual-Fuel Propelled Nanomotors with Two-Stage Permeation for Deep Bacterial Infection in the Treatment of Pulpitis.

Bacterial infection-induced inflammatory response could cause irreversible death of pulp tissue in the absence of timely and effective therapy. Given that, the narrow structure of root canal limits the therapeutic effects of passive diffusion-drugs, considerable attention has been drawn to the development of nanomotors, which have high tissue penetration abilities but generally face the problem of insufficient fuel concentration. To address this drawback, dual-fuel propelled nanomotors (DPNMs) by encapsulating L-arginine (L-Arg), calcium peroxide (CaO2 ) in metal-organic framework is developed. Under pathological environment, L-Arg could release nitric oxide (NO) by reacting with reactive oxygen species (ROS) to provide the driving force for movement. Remarkably, the depleted ROS could be supplemented through the reaction between CaO2 with acids abundant in the inflammatory microenvironment. Owing to high diffusivity, NO achieves further tissue penetration based on the first-stage propulsion of nanomotors, thereby removing deep-seated bacterial infection. Results indicate that the nanomotors effectively eliminate bacterial infection based on antibacterial activity of NO, thereby blocking inflammatory response and oxidative damage, forming reparative dentine layer to avoid further exposure and infection. Thus, this work provides a propagable strategy to overcome fuel shortage and facilitates the therapy of deep lesions.

Targeting mitochondrial quality control for diabetic cardiomyopathy: Therapeutic potential of hypoglycemic drugs.

Diabetic cardiomyopathy is a chronic cardiovascular complication caused by diabetes that is characterized by changes in myocardial structure and function, ultimately leading to heart failure and even death. Mitochondria serve as the provider of energy to cardiomyocytes, and mitochondrial dysfunction plays a central role in the development of diabetic cardiomyopathy. In response to a series of pathological changes caused by mitochondrial dysfunction, the mitochondrial quality control system is activated. The mitochondrial quality control system (including mitochondrial biogenesis, fusion and fission, and mitophagy) is core to maintaining the normal structure of mitochondria and performing their normal physiological functions. However, mitochondrial quality control is abnormal in diabetic cardiomyopathy, resulting in insufficient mitochondrial fusion and excessive fission within the cardiomyocyte, and fragmented mitochondria are not phagocytosed in a timely manner, accumulating within the cardiomyocyte resulting in cardiomyocyte injury. Currently, there is no specific therapy or prevention for diabetic cardiomyopathy, and glycemic control remains the mainstay. In this review, we first elucidate the pathogenesis of diabetic cardiomyopathy and explore the link between pathological mitochondrial quality control and the development of diabetic cardiomyopathy. Then, we summarize how clinically used hypoglycemic agents (including sodium-glucose cotransport protein 2 inhibitions, glucagon-like peptide-1 receptor agonists, dipeptidyl peptidase-4 inhibitors, thiazolidinediones, metformin, and α-glucosidase inhibitors) exert cardioprotective effects to treat and prevent diabetic cardiomyopathy by targeting the mitochondrial quality control system. In addition, the mechanisms of complementary alternative therapies, such as active ingredients of traditional Chinese medicine, exercise, and lifestyle, targeting mitochondrial quality control for the treatment of diabetic cardiomyopathy are also added, which lays the foundation for the excavation of new diabetic cardioprotective drugs.

Efficacy and safety of non-pharmacological therapy under the guidance of TCM theory in the treatment of anxiety in patients with myocardial infarction: A protocol for systematic review and meta-analysis.

BACKGROUND: With the increasing pressures of modern life and work, combined with a growing older population, the incidence of comorbid anxiety and myocardial infarction (MI) is increasing. Anxiety increases the risk of adverse cardiovascular events in patients with MI and significantly affects their quality of life. However, there is an ongoing controversy regarding the pharmacological treatment of anxiety in patients with MI. The concomitant use of commonly prescribed selective serotonin reuptake inhibitors (SSRIs) and antiplatelet medications such as aspirin and clopidogrel may increase the risk of bleeding. Conventional exercise-based rehabilitation therapies have shown limited success in alleviating anxiety symptoms. Fortunately, non-pharmacological therapies based on traditional Chinese medicine (TCM) theory, such as acupuncture, massage, and qigong, have demonstrated promising efficacy in treating MI and comorbid anxiety. These therapies have been widely used in community and tertiary hospital settings in China to provide new treatment options for patients with anxiety and MI. However, current studies on non-pharmacological TCM-based therapies have predominantly featured small sample sizes. This study aims to comprehensively analyze and explore the effectiveness and safety of these therapies in treating anxiety in patients with MI. METHOD: We will systematically search six English and four Chinese databases by employing a pre-defined search strategy and adhering to the unique rules and regulations of each database to identify studies that fulfilled our inclusion criteria, to qualify for inclusion, patients must be diagnosed with both MI and anxiety, and they must have undergone non-pharmacological TCM therapies, such as acupuncture, massage, or qigong, whereas the control group received standard treatments. The primary outcome measure will be alterations in anxiety scores, as assessed using anxiety scales, with secondary outcomes encompassing the evaluations of cardiopulmonary function and quality of life. We will utilize RevMan 5.3 to conduct a meta-analysis of the collected data, and subgroup analyses will be executed based on distinct types of non-pharmacological TCM therapies and outcome measures. RESULTS: A narrative summary and quantitative analysis of the existing evidence on the treatment of anxiety patients with MI using non-pharmacological therapies guided by Traditional Chinese Medicine theory. CONCLUSION: This systematic review will investigate whether non-pharmacological interventions guided by TCM theory are effective and safe for anxiety in patients with MI, and provide evidence-based support for their clinical application. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022378391.

ß-tubulin contributes to Tongyang Huoxue decoction-induced protection against hypoxia/reoxygenation-induced injury of sinoatrial node cells through SIRT1-mediated regulation of mitochondrial quality surveillance.

BACKGROUND: TYHX-Tongyang Huoxue decoction has been used clinically for nearly 40 years. The ingredients of TYHX are Radix Astragali (Huangqi), Red Ginseng (Hongshen), Rehmannia Glutinosa (Dihuang), Common Yam Rhizome (Shanyao) and Cassia-bark-tree Bark (Rougui). Our previous experiments confirmed that TYHX can protect sinoatrial node cells. However, its mechanism of action is not completely understood yet. PURPOSE: The present study aimed to determine the protective effects of TYHX against Sinus node cell injury under hypoxic stress and elucidate the underlying mechanisms of protection. METHODS: Through RNA sequencing analysis and network pharmacology analysis, we found significant differences in mitochondrial-related genes before and after hypoxia-mimicking SNC, resolved the main regulatory mechanism of TYHX. Through the intervention of TYHX on SNC, a series of detection methods such as laser confocal, fluorescence co-localization, mitochondrial membrane potential and RT-PCR. The regulatory effect of TYHX on ß-tubulin in sinoatrial node cells was verified by in vitro experiments. The mechanism of action of TYHX and its active ingredient quercetin to maintain mitochondrial homeostasis and protect sinoatrial node cells through mitophagy, mitochondrial fusion/fission and mitochondrial biosynthesis was confirmed. RESULTS: Through RNA sequencing analysis, we found that there were significant differences in mitochondrial related genes before and after SNC was modeled by hypoxia. Through pharmacological experiments, we showed that TYHX could inhibit the migration of Drp1 to mitochondria, inhibit excessive mitochondrial fission, activate mitophagy and increase the mitochondrial membrane potential. These protective effects were mainly mediated by ß-tubulin. Furthermore, the active component quercetin in TYHX could inhibit excessive mitochondrial fission through SIRT1, maintain mitochondrial energy metabolism and protect SNCs. Our results showed that protection of mitochondrial function through the maintenance of ß-tubulin and activation of SIRT1 is the main mechanism by which TYHX alleviates hypoxic stress injury in SNCs. The regulatory effects of TYHX and quercetin on mitochondrial quality surveillance are also necessary. Our findings provide empirical evidence supporting the use of TYHX as a targeted treatment for sick sinus syndrome. CONCLUSION: Our data indicate that TYHX exerts protective effects against sinus node cell injury under hypoxic stress, which may be associated with the regulation of mitochondrial quality surveillance (MQS) and inhibition of mitochondrial homeostasis-mediated apoptosis.

Targeting epigenetics in diabetic cardiomyopathy: Therapeutic potential of flavonoids.

The pathophysiological mechanisms of diabetic cardiomyopathy have been extensively studied, but there is still a lack of effective prevention and treatment methods. The ability of flavonoids to protect the heart from diabetic cardiomyopathy has been extensively described. In recent years, epigenetics has received increasing attention from scholars in exploring the etiology and treatment of diabetes and its complications. DNA methylation, histone modifications and non-coding RNAs play key functions in the development, maintenance and progression of diabetic cardiomyopathy. Hence, prevention or reversal of the epigenetic alterations that have occurred during the development of diabetic cardiomyopathy may alleviate the personal and social burden of the disease. Flavonoids can be used as natural epigenetic modulators in alternative therapies for diabetic cardiomyopathy. In this review, we discuss the epigenetic effects of different flavonoid subtypes in diabetic cardiomyopathy and summarize the evidence from preclinical and clinical studies that already exist. However, limited research is available on the potential beneficial effects of flavonoids on the epigenetics of diabetic cardiomyopathy. In the future, clinical trials in which different flavonoids exert their antidiabetic and cardioprotective effects through various epigenetic mechanisms should be further explored.

Roles and mechanisms of quercetin on cardiac arrhythmia: A review.

Cardiac arrhythmia is one of the most prevalent cardiovascular diseases worldwide, which can occur alone or be triggered by other diseases, and it can be fatal in severe cases. Recently, Traditional Chinese Medicine has drawn the world's attention to its effective treatment. As a natural polyhydroxy flavonoid mainly isolated from a variety of plants and foods, quercetin is used for the treatment of cardiovascular disease, cancer, autoimmune diseases, and neurological disorders. A growing number of in vitro experiments and in vivo animal studies have shown that quercetin significantly inhibits mitochondrial oxidative stress, cardiac fibrosis, inflammatory responses, and apoptosis, regulates autophagic responses, improves ischemia/reperfusion injury in cardiomyocytes, and regulates gut microbiota, thereby attenuating or preventing structural and electrical remodeling in the cardiac. Based on these mechanisms, our review provides a systematic overview of the pharmacological actions and molecular targets of quercetin in cardiac arrhythmia caused by multiple etiologies, aiming to provide novel insights and therapeutic strategies to prevent or ameliorate arrhythmia.