Autonomic and endocrine control of cardiovascular function

The function of the heart is to contract and pump oxygenated blood to the body and deoxygenated blood to the lungs.To achieve this goal,a normal human heart must beat regularly and continuously for one's entire life.Heartbeats originate from the rhythmic pacing discharge from the sinoatrial(SA) node within the heart itself.In the absence of extrinsic neural or hormonal influences,the SA node pacing rate would be about 100 beats per minute.Heart rate and cardiac output,however,must vary in response to the needs of the body's cells for oxygen and nutrients under varying conditions.In order to respond rapidly to the changing requirements of the body's tissues,the heart rate and contractility are regulated by the nervous system,hormones,and other factors.Here we review how the cardiovascular system is controlled and influenced by not only a unique intrinsic system,but is also heavily influenced by the autonomic nervous system as well as the endocrine system.

Oxidative stress-mediated effects of angiotensin Ⅱ in the cardiovascular system

Angiotensin Ⅱ(Ang Ⅱ), an endogenous peptide hormone, plays critical roles in the pathophysiological modulation of cardiovascular functions. Ang Ⅱ is the principle effector of the renin-angiotensin system for maintaining homeostasis in the cardiovascular system, as well as a potent stimulator of NAD(P)H oxidase, which is the major source and primary trigger for reactive oxygen species(ROS) generation in various tissues. Recent accumulating evidence has demonstrated the importance of oxidative stress in Ang Ⅱ-induced heart diseases. Here, we review the recent progress in the study on oxidative stress-mediated effects of Ang Ⅱ in the cardiovascular system. In particular, the involvement of Ang Ⅱ-induced ROS generation in arrhythmias, cell death/heart failure, ischemia/reperfusion injury, cardiac hypertrophy and hypertension are discussed. Ca2+/calmodulin-dependent protein kinase Ⅱ is an important molecule linking Ang Ⅱ, ROS and cardiovascular pathological conditions.

Modulatory effects of Lactiplantibacillus plantarum on chronic metabolic diseases

The increased global incidence of chronic metabolic diseases,a vital threat to human health and a burden on our healthcare systems,includes a series of clinical metabolic syndromes such as obesity,diabetes,hypertension,and dyslipidemia.One of the well-known probiotic microorganisms,Lactiplantibacillus plantarum plays an important role in promoting human health,including inhibiting the occurrence and development of a variety of chronic metabolic diseases.The present study provides an overview of the preventive and therapeutic effects of L.plantarum on diabetes,obesity,non-alcoholic fatty liver disease,kidney stone disease,and cardiovascular diseases in animal models and human clinical trials.Ingesting L.plantarum demonstrated its ability to reduce inflammatory and oxidative stress levels by regulating the production of cytokines and short-chain fatty acids(SCFAs),the activity of antioxidant enzymes,and the balance of intestinal microbial communities to alleviate the symptoms of chronic metabolic diseases.Furthermore,updated applications and technologies of L.plantarum in food and biopharmaceutical industries are also discussed.Understanding the characteristics and functions of L.plantarum will guide the development of related probiotic products and explore the modulatory benefit of L.plantarum supplementations on the prevention and treatment of multiple chronic metabolic diseases.

Atomic force microscopy reveals new mechanisms of increased aortic stiffness in hypertension

Hypertension is an important global health problem that continues increase in incidence.Increased vascularstiffness has been identified as an important component of the pathogenesis of hypertension(HT).Based on theresults of recent Framingham studies,it appears that aortic increased stiffness may precede hypertension suggest-ing that controlling arterial stiffness may

Fatty acid oxidation and autophagy promote endoxifen resistance and counter the effect of AKT inhibition in ER-positive breast cancer cells

Tamoxifen(TAM)is the first-line endocrine therapy for estrogen receptor-positive(ER+)breast cancer(BC).However,acquired resistance occurs in∼50%cases.Meanwhile,although the PI3K/AKT/mTOR pathway is a viable target for treatment of endocrine therapy-refractory patients,complex signaling feedback loops exist,which can counter the effectiveness of inhibitors of this pathway.Here,we analyzed signaling pathways and metabolism in ER+MCF7 BC cell line and their TAM-resistant derivatives that are co-resistant to endoxifen using immunoblotting,quantitative polymerase chain reaction,and the Agilent Seahorse XF Analyzer.We found that activation of AKT and the energy-sensing kinase AMPK was increased in TAM and endoxifen-resistant cells.Furthermore,ERRα/PGC-1βand their target genes MCAD and CPT-1 were increased and regulated by AMPK,which coincided with increased fatty acid oxidation(FAO)and autophagy in TAM-resistant cells.Inhibition of AKT feedback-activates AMPK and ERRα/PGC-1β-MCAD/CPT-1 with a consequent increase in FAO and autophagy that counters the therapeutic effect of endoxifen and AKT inhibitors.Therefore,our results indicate increased activation of AKT and AMPK with metabolic reprogramming and increased autophagy in TAM-resistant cells.Simultaneous inhibition of AKT and FAO/autophagy is necessary to fully sensitize resistant cells to endoxifen.

iPSC-derived cranial neural crest-like cells can replicate dental pulp tissue with the aid of angiogenic hydrogel

The dental pulp has irreplaceable roles in maintaining healthy teeth and its regeneration is a primary aim of regenerative endodontics.This study aimed to replicate the characteristics of dental pulp tissue by using cranial neural crest(CNC)-like cells(CNCLCs);these cells were generated by modifying several steps of a previously established method for deriving NC-like cells from induced pluripotent stem cells(iPSCs).CNC is the anterior region of the neural crest in vertebrate embryos,which contains the primordium of dental pulp cells or odontoblasts.The produced CNCLCs showed approximately 2.5-12,000-fold upregulations of major CNC marker genes.Furthermore,the CNCLCs exhibited remarkable odontoblastic differentiation ability,especially when treated with a combination of the fibroblast growth factors(FGFs)FGF4 and FGF9.The FGFs induced odontoblast marker genes by 1.7-5.0-fold,as compared to bone morphogenetic protein 4(BMP4)treatment.In a mouse subcutaneous implant model,the CNCLCs briefly fated with FGF4+FGF9 replicated dental pulp tissue characteristics,such as harboring odontoblast-like cells,a dentin-like layer,and vast neovascularization,induced by the angiogenic self-assembling peptide hydrogel(SAPH),SLan.SLan acts as a versatile biocompatible scaffold in the canal space.This study demonstrated a successful collaboration between regenerative medicine and SAPH technology.

Erratum: P53-regulated autophagy and its impact on drug resistance and cell fate

The original article was published on 19 Mar 2021,and the original article link is https://cdrjournal.com/article/view/3789 The corresponding author declared that The Department of Defense Grant support acknowledgment was incorrectly entered.The Department of Defense Grant award that helped support this work was W81XWH-16-1-0025.Therefore,he needed to change financial support and sponsorship in his publication in our journal.According to the evidence provided by the corresponding author,this work was supported by the National Cancer Institute Grant(R01CA200232-05)and the Department of Defense Grant(W81XWH-16-1-0025)both to Maki CG,and all of the other authors of this paper agreed with the change mentioned above.Therefore,we publish this erratum to announce this change.

P53-regulated autophagy and its impact on drug resistance and cell fate

Wild-type p53 is a stress-responsive transcription factor and a potent tumor suppressor.P53 inhibits the growth of incipient cancer cells by blocking their proliferation or inducing their death through apoptosis.Autophagy is a self-eating process that plays a key role in response to stress.During autophagy,organelles and other intracellular components are degraded in autophagolysosomes and the autophagic breakdown products are recycled into metabolic and energy producing pathways needed for survival.P53 can promote or inhibit autophagy depending on its subcellular localization,mutation status,and the level of stress.Blocking autophagy has been reported in several studies to increase p53-mediated apoptosis,revealing that autophagy can influence cell-fate in response to activated p53 and is a potential target to increase p53-dependent tumor suppression.