Modified Transannular Patching Palliation versus Modified Blalock-Taussig-Thomas Shunt in Infants with Severe Tetralogy of Fallot with Diminutive Pulmonary Arteries.

OBJECTIVE: The purpose of this study was to compare pulmonary arterial (PA) growth and morbidity, mortality, reintervention and complete repair rates after modified transannular patching palliation (mTAP) versus modified Blalock-Taussig-Thomas shunt (mBTS) for palliation in infants with severe tetralogy of Fallot (TOF) with diminutive pulmonary arteries. METHODS: This was a retrospective case review study of 107 patients (64 males) with severe TOF who underwent staged repair with either mTAP (n = 55) or mBTS (n = 52) over an 8-year period. Procedure-related PA growth and morbidity, mortality, reintervention and complete repair rates were compared. RESULTS: Two deaths occurred in the mBTS group due to sudden cardiac arrest, and five patients needed reintervention after the mBTS procedure because of shunt thrombosis or stenosis. Postoperative complications of mBTS included sudden cardiac arrest, shunt thrombosis/stenosis, vocal cord palsy and diaphragmatic palsy. Unlike in the mBTS group, no death, severe complications or reintervention occurred in the mTAP group. Oxygen saturations post mTAP and mBTS were significantly higher, which improved from 67.73 ± 4.36% to 94.33 ± 2.19% in the mTAP group and from 68.24 ± 3.87% to 86.87 ± 3.38% in the mBTS group. The increase in oxygen saturation and pulmonary artery growth (from pre- to post palliation) was significantly better with mTAP than with mBTS palliation (p < 0.01). All 55 patients showed complete repair after mTAP, and the time from palliation to complete repair was significantly shorter in the mTAP group. CONCLUSIONS: In a severe form of TOF with the hypoplastic PA tree, mTAP seems to be a better strategy that is safe and better facilitates satisfactory pulmonary arterial growth until complete repair than the mBTS procedure.

Paeonol promotes Opa1-mediated mitochondrial fusion via activating the CK2α-Stat3 pathway in diabetic cardiomyopathy.

Diabetes disrupts mitochondrial function and often results in diabetic cardiomyopathy (DCM). Paeonol is a bioactive compound that has been reported to have pharmacological potential for cardiac and mitochondrial protection. This study aims to explore the effects of paeonol on mitochondrial disorderes in DCM and the underlying mechanisms. We showed that paeonol promoted Opa1-mediated mitochondrial fusion, inhibited mitochondrial oxidative stress, and preserved mitochondrial respiratory capacity and cardiac performance in DCM in vivo and in vitro. Knockdown of Opa1 blunted the above protective effects of paeonol in both diabetic hearts and high glucose-treated cardiomyocytes. Mechanistically, inhibitor screening, siRNA knockdown and chromatin immunoprecipitation experiments showed that paeonol-promoted Opa1-mediated mitochondrial fusion required the activation of Stat3, which directly bound to the promoter of Opa1 to upregulate its transcriptional expression. Moreover, pharmmapper screening and molecular docking studies revealed that CK2α served as a direct target of paeonol that interacted with Jak2 and induced the phosphorylation and activation of Jak2-Stat3. Knockdown of CK2α blunted the promoting effect of paeonol on Jak2-Stat3 phosphorylation and Opa1-mediated mitochondrial fusion. Collectively, we have demonstrated for the first time that paeonol is a novel mitochondrial fusion promoter in protecting against hyperglycemia-induced mitochondrial oxidative injury and DCM at least partially via an Opa1-mediated mechanism, a process in which paeonol interacts with CK2α and restores its kinase activity that subsequently increasing Jak2-Stat3 phosphorylation and enhancing the transcriptional level of Opa1. These findings suggest that paeonol or the promotion of mitochondrial fusion might be a promising strategy for the treatment of DCM.

Analysis of 85 Cases of Minimal Media Lower Hemisternotomy for Congenital Cardiac Surgery Under Cardiopulmonary Bypass in Infants.

OBJECTIVE: To investigate the feasibility and effect of minimal media lower hemisternotomy for cardiac surgery under cardiopulmonary bypass (CPB) in infant congenital heart disease. METHODS: In our hospital from May 2019 to October 2019, 170 infants with congenital heart disease underwent surgical treatment (median age 6.6 months; weight 6.0 kg). They were divided into 2 groups: those with conventional chest median incision and those with minimal sternotomy. Minimal lower hemisternotomy began from the third intercostal level and ended 0.5 cm above the xiphoid, just enough to insert a small sternal distractor. RESULTS: There was no significant difference between the 2 groups in CPB time. The operation time of small incision group was slightly longer (P < .05). There was no difference in prognosis between the 2 groups, but the wound length of the small incision group was significantly reduced (4.0 ± 0.5 versus 7.8 ± 0.8 cm, P < .05). Time of intensive care unit and hospital stay was shorter among hemisternotomy patients at a statistically significant level (P < .05). CONCLUSION: Minimal media lower hemisternotomy with the basic advantages of the sternal incision can expose the various parts of the heart, which meets most cardiac exploration and surgical operation needs, and the incision may still be extended if necessary. Lower hemisternotomy appears to be a safe, effective, and versatile alternative for many surgical interventions in infants with congenital heart disease.

CCR9 and CCL25: A review of their roles in tumor promotion.

Chemokines constitute a superfamily of small chemotactic cytokines with functions that are based on interactions with their corresponding receptors. It has been found that, among other functions, chemokines regulate the migratory and invasive abilities of cancer cells. Multiple studies have confirmed that chemokine receptor 9 (CCR9) and its exclusive ligand, chemokine 25 (CCL25), are overexpressed in a variety of malignant tumors and are closely associated with tumor proliferation, apoptosis, invasion, migration and drug resistance. This review evaluates recent advances in understanding the role of CCR9/CCL25 in cancer development. First, we outline the general background of chemokines in cancer and the structure and function of CCR9 and CCL25. Next, we describe the basic function of CCR9/CCL25 in the cancer process. Then, we introduce the role of CCR9/CCL25 and related signaling pathways in various cancers. Finally, future research directions are proposed. In general, this paper is intended to serve as a comprehensive repository of information on this topic and is expected to contribute to the design of other research projects and future efforts to develop treatment strategies for ameliorating the effects of CCR9/CCL25 in cancer.

Mammalian Sterile 20-Like Kinase (MST) 1/2: Crucial Players in Nervous and Immune System and Neurological Disorders.

As central components of the Hippo signaling pathway in mammals, the mammalian sterile 20-like kinase 1 (MST1) and MST2 protein kinases regulate cell proliferation, survival, and death and are involved in the homeostasis of many tissues. Recent studies have elucidated the roles of MST1 and MST2 in the nervous system and immune system, particularly in neurological disorders, which are influenced by aging. In this review, we provide a comprehensive overview of these research areas. First, the activation mechanisms and roles of MST1 and MST2 in neurons, non-neuronal cells, and immune cells are introduced. The roles of MST1 and MST2 in neurological disorders, including brain tumors, cerebrovascular diseases, neurodegenerative disorders, and neuromuscular disorders, are then presented. Finally, the existing obstacles for further research are discussed. Collectively, the information compiled herein provides a common framework for the function of MST1 and MST2 in the nervous system, should contribute to the design of further experiments, and sheds light on potential treatments for aging associated neurological disorders.

Aortic regurgitation after closure of ventricular septal defect by transcatheter device: the long-term complication.

Ventricular septal defect is the most common type of CHD, and transcatheter ventricular septal defect closure has been shown to be an alternative to surgical closure with acceptable mortality and morbidity as well as encouraging results. Short-term and mid-term follow-ups have indicated the safety and efficacy of transcatheter closure, but long-term follow-up results were rare. In this report, we first found that aortic regurgitation occurred in patients 9-12 years following transcatheter closure and regurgitation were gradually increased. The findings indicate that the long-term outcome of transcatheter closure of ventricular septal defect may not be as satisfied as expected.

Metformin mediates cardioprotection against aging-induced ischemic necroptosis.

Necroptosis is crucially involved in severe cardiac pathological conditions. However, whether necroptosis contributes to age-related intolerance to ischemia/reperfusion (I/R) injury remains elusive. In addition, metformin as a potential anti-aging related injury drug, how it interacts with myocardial necroptosis is not yet clear. Male C57BL/6 mice at 3-4- (young) and 22-24 months of age (aged) and RIPK3-deficient (Ripk3-/- ) mice were used to investigate aging-related I/R injury in vivo. Metformin (125 µg/kg, i.p.), necrostatin-1 (3.5 mg/kg), and adenovirus vector encoding p62-shRNAs (Ad-sh-p62) were used to treat aging mice. I/R-induced myocardial necroptosis was exaggerated in aged mice, which correlated with autophagy defects characterized by p62 accumulation in aged hearts or aged human myocardium. Functionally, blocking autophagic flux promoted H/R-evoked cardiomyocyte necroptosis in vitro. We further revealed that p62 forms a complex with RIP1-RIP3 (necrosome) and promotes the binding of RIP1 and RIP3. In mice, necrostatin-1 treatment (a RIP1 inhibitor), RIP3 deficiency, and cardiac p62 knockdown in vivo demonstrated that p62-RIP1-RIP3-dependent myocardial necroptosis contributes to aging-related myocardial vulnerability to I/R injury. Notably, metformin treatment disrupted p62-RIP1-RIP3 complexes and effectively repressed I/R-induced necroptosis in aged hearts, ultimately reducing mortality in this model. These findings highlight previously unknown mechanisms of aging-related myocardial ischemic vulnerability: p62-necrosome-dependent necroptosis. Metformin acts as a cardioprotective agent that inhibits this unfavorable chain mechanism of aging-related I/R susceptibility.

Novel role of sex-determining region Y-box 7 (SOX7) in tumor biology and cardiovascular developmental biology.

The sex-determining region Y-box 7 (Sox7) is an important member of the SOX F family, which is characterized by a high-mobility-group DNA-binding domain. Previous studies have demonstrated the role of SOX7 in cardiovascular development. SOX7 expression could be detected in normal adult tissues. Furthermore, the expression levels of SOX7 were different in different tumors. Most studies showed the downregulation of SOX7 in tumors, while some studies reported its upregulation in tumors. In this review, we first summarized the upstream regulators (including transcription factors, microRNAs (miRNAs), long noncoding RNAs (lncRNAs) and some exogenous regulators) and downstream molecules (including factors in the Wnt/ß-catenin signaling pathway and some other signaling pathways) of SOX7. Then, the roles of SOX7 in multiple tumors were presented. Finally, the significance of divergent SOX7 expression during cardiovascular development was briefly discussed. The information compiled in this study characterized SOX7 during tumorigenesis and cardiovascular development, which should facilitate the design of future research and promote SOX7 as a therapeutic target.

Targeted inhibition of STAT3 as a potential treatment strategy for atherosclerosis.

Atherosclerosis is the main pathological basis of ischemic cardiovascular and cerebrovascular diseases and has attracted more attention in recent years. Multiple studies have demonstrated that the signal transducer and activator of transcription 3 (STAT3) plays essential roles in the process of atherosclerosis. Moreover, aberrant STAT3 activation has been shown to contribute to the occurrence and development of atherosclerosis. Therefore, the study of STAT3 inhibitors has gradually become a focal research topic. In this review, we describe the crucial roles of STAT3 in endothelial cell dysfunction, macrophage polarization, inflammation, and immunity during atherosclerosis. STAT3 in mitochondria is mentioned as well. Then, we present a summary and classification of STAT3 inhibitors, which could offer potential treatment strategies for atherosclerosis. Furthermore, we enumerate some of the problems that have interfered with the development of mature therapies utilizing STAT3 inhibitors to treat atherosclerosis. Finally, we propose ideas that may help to solve these problems to some extent. Collectively, this review may be useful for developing future STAT3 inhibitor therapies for atherosclerosis.

Akt is a critical node of acute myocardial insulin resistance and cardiac dysfunction after cardiopulmonary bypass.

AIMS: Acute myocardial insulin resistance is an independent risk factor for patients who undergo cardiac surgery with cardiopulmonary bypass (CPB). However, the underlying mechanism of insulin resistance during CPB has not been fully investigated. MATERIALS AND METHODS: To explore the role of myocardial insulin resistance on the cardiac function and its underlying mechanism, CPB operation and pharmacological intervention were applied in mini pigs, and myocardial insulin signaling, glucose uptake, ATP production and cardiac function were examined. KEY FINDINGS: Our data showed that CPB elicited not only hyperglycemia and hyperinsulinemia, but also inactivated Akt, and impaired the transposition of membrane glucose transporter-4 (GLUT-4), reduced glucose uptake and ATP production in the myocardium as well, which in turn was accompanied with cardiac dysfunction. Meanwhile, linear correlations were established among reduced myocardial glucose uptake, ATP production, and depressed cardiac systolic or diastolic function. Reactivation of Akt by SC79, an Akt agonist, partially alleviated myocardial insulin resistance and restored post CPB cardiac function via augmenting myocardial glucose uptake and ATP production. SIGNIFICANCE: These findings revealed that acute myocardial insulin resistance due to inactivation of Akt played a key role in cardiac dysfunction post CPB via suppressing glucose metabolism related energy supply.

Endoplasmic reticulum stress and NLRP3 inflammasome: Crosstalk in cardiovascular and metabolic disorders.

When endoplasmic reticulum (ER) homeostasis is disrupted, known as ER stress (ERS), the ER generates an adaptive signaling pathway called the unfolded protein response to maintain the homeostasis of this organelle. However, if homeostasis is not restored, the ER initiates death signaling pathways, which contribute to the pathogenesis of various disorders. The activation of inflammatory mechanisms is also emerging as a crucial component of cardiovascular and metabolic disorders. Furthermore, the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome has attracted more attention than others and is the best-characterized member of the NLR family of inflammasomes to date. ERS intersects with many different inflammatory pathways, particularly the NLRP3 inflammasome. In this review, we focus on the interactions between ERS and the NLRP3 inflammasome. The pharmacologic and nonpharmaceutical manipulation of these two processes may offer novel opportunities for the treatment of cardiovascular and metabolic disorders.

Bakuchiol: A newly discovered warrior against organ damage.

Bakuchiol (BAK), [(1E,3S)-3-ethenyl-3,7-dimethyl-1,6-octadien-1-yl]phenol is a prenylated phenolic monoterpene extracted from the fruit of Psoralea corylifolia L., which belongs to the Leguminosae plant family. Previous research has shown that BAK exerts a variety of pharmacological effects, including antioxidant, antibacterial, anti-inflammatory, antiaging and estrogen-like effects. In addition, recent studies have indicated that BAK exerts protective effects in the heart, liver, skin and other organs. BAK treatment protects the heart against ischemia-reperfusion injury through modulating cardioprotective pathways. BAK also inhibits liver fibrosis via promoting myofibroblast apoptosis and relieves the hepatotoxicity of multiple toxicants by suppressing oxidative stress and inflammatory changes. BAK inhibits the proliferation of various cancer cells, including stomach, breast and skin cancer cells, thereby exerting anticancer effects. Further, BAK effectively slows skin aging by preserving skin collagen. BAK treatment can protect against bone loss and delay osteoporosis by exerting estrogen-like effects. In addition, BAK remarkably reduces blood glucose and triglycerides and might be a potential pharmacological agent that can be used to protect against pancreatic beta-cell damage and diabetes progression. In this review, the pharmacological mechanisms and protective effects of BAK in human diseases are discussed, with a focus on the protective effects of BAK in the heart, liver and other important organs.

Forkhead box O4 transcription factor in human neoplasms: Cannot afford to lose the novel suppressor.

Forkhead box O4 (FOXO4), a member of FOXO family, has been highlighted as an essential transcriptional regulator in many diverse carcinomas. Accumulated studies have demonstrated that FOXO4 is downregulated and associated with tumorigenesis, invasiveness, and metastasis of most human cancer. FOXO4 alteration is also closely linked to the prognosis of various types of cancer. The aim of this review is to comprehensively present the clinical and pathological significance of FOXO4 in human cancer. Additionally, the potential clinical applications of future FOXO4 research are discussed. Collectively, the information reviewed here should increase the potential of FOXO4 as a therapeutic target for cancer.

Three-dimensional printed degradable splint in the treatment of pulmonary artery sling associated with severe bilateral bronchus stenosis.

Pulmonary artery sling is a congenital cardiovascular disease and is usually accompanied by tracheobronchial stenosis. Generally, infants diagnosed with pulmonary artery sling should have surgery. However, the treatment of tracheobronchial stenosis is still controversial. Our team developed a customised, degradable, three-dimensional printed splint and successfully applied it in the treatment of pulmonary artery sling associated with severe bilateral bronchus stenosis. We suggested that three-dimensional printing may be a novel and effective way to treat tracheobronchial stenosis and other diseases in children.

Activation of AMPK alleviates cardiopulmonary bypass-induced cardiac injury via ameliorating acute cardiac glucose metabolic disorder.

Recent years, studies have demonstrated that hyperglycemia is one of the main manifestations after cardiac surgeries, which contributes to myocardial injuries and increases the chance of subsequent complications and mortality in such patients. However, strategies targeting at glucose metabolic disorder after cardiac surgeries to attenuate myocardial injuries are inadequately studied. In this study, a rat model of cardiopulmonary bypass (CPB) was applied to investigate the role of Adenosine 5'-monophosphate-activated protein kinase (AMPK) in modulating myocardial glucose metabolic-induced cardiac injuries after cardiac surgery. The results revealed that CPB elicited significant cardiac dysfunction, and pronouncedly elevated the markers of myocardial injuries including serum creatine kinase MB and cardiac troponin I. Additionally, blunted myocardial glucose uptake after CPB was associated with decreased membrane glucose transporter 4 (GLUT4) content. However, pretreatment of AMPK agonist 5-aminoimidazole-4-carboxamide1-ß-D-ribofuranoside (AICAR) at the beginning of CPB activated AMPK, enhanced phosphorylation of Akt substrate 160 (AS160), and increased myocardial membrane content of GLUT4. Meanwhile, improved myocardial glucose uptake and more importantly alleviated cardiac injury were also observed after CPB pretreated with AICAR. Moreover, the application of a mutant form of AS160 (AS160-4P) abolished the beneficial effect of AICAR, as evidenced by impaired cardiac glucose uptake, reduced myocardial membrane GLUT-4 translocation, increased cardiac injury markers, and deterioration of cardiac function after CPB. In conclusion, it was suggested in this study that preactivation of AMPK by AICAR improved myocardial glucose uptake by promoting AS160 dependent myocardial membrane GLUT-4 translocation, which ultimately provided a potent cardioprotective effect.

Tetramethylpyrazine Protects Against Glucocorticoid-Induced Apoptosis by Promoting Autophagy in Mesenchymal Stem Cells and Improves Bone Mass in Glucocorticoid-Induced Osteoporosis Rats.

Glucocorticoid-induced osteoporosis (GIOP) is a widespread clinical complication due to the common use of glucocorticoids. Excess glucocorticoids induce apoptosis of bone marrow-derived mesenchymal stem cells (BMSCs), which have been shown to play an increasingly important role in the pathogenesis and therapy of osteoporosis. Tetramethylpyrazine (TMP), an extract from one of the most recognized herbs in traditional Chinese medicine (Chuanxiong), has been reported to have antiapoptotic properties. In this study, we tested whether TMP protects rat BMSCs following exposure to glucocorticoids in vitro and in vivo. We treated BMSCs with different concentrations of TMP (50, 100, or 200 µM) and exposed them to 10-6 M dexamethasone (Dex) for 48 h in vitro. Our data showed that TMP inhibited Dex-induced cytotoxicity and protected BMSCs from apoptosis. Interestingly, further results demonstrated that TMP prevented apoptosis in BMSCs by promoting autophagy in an AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) pathway-dependent manner. In addition, calcein fluorescence double labeling and microcomputed tomography scanning indicated that 12 weeks of TMP administration augmented bone formation and protected trabecular bone mass in GIOP rats. We also discovered that first-passage BMSCs isolated from the TMP treatment group had a lower rate of apoptosis and a higher light chain 3 (LC3)-II/LC3-I ratio than the GIOP group. Our findings demonstrate for the first time that TMP can protect BMSCs from exposure to excess glucocorticoids by promoting autophagy through AMPK/mTOR pathway and might be an effective agent for the prevention and treatment of GIOP.

Expression of CD147, PCNA, VEGF, MMPs and their clinical significance in the giant cell tumor of bones.

BACKGROUND: Giant cell tumor of bone (GCT) is a potentially malignant tumor. CD147 is a multifunctional protein, which expresses itself in many tumors. In this study, we have investigated the correlation between CD147 and PCNA, VEGF, MMPs expression in giant cell tumor of bones. We have also explored the relationship between its clinical pathology and prognosis. RESULTS: A significant difference of the expression level of CD147, MMPs was found in cases of GCT with Jaffe grading and prognosis (P<0.05). But, it was not in accordance with the patient's age and sex. An expression of CD147 was positively correlated with MMP-9, VEGF, MVD, PCNA (r=0.271, P=0.025; r=0.411, P=0.000; r=0.872, P=0.000; r=0.394, P=0.001). CONCLUSION: The expression level of CD147 in giant cell tumors of bones is correlated with the development of cancers and relapse. There was a positive correlation between expressions of CD147 and MMP-9, VEGF, MVD, PCNA, and CD147. This is an important indicator in evaluating the malignant degree and prognosis of giant cell tumors of bone. It may be the new target for ensuring chemopreventive strategies.

Glucocorticoids: Dose-related effects on osteoclast formation and function via reactive oxygen species and autophagy.

Whether glucocorticoids directly enhance or interrupt osteoclastogenesis is still a controversial subject. In this study, we ascertained the dose-dependent positive effects of glucocorticoids on osteoclastogenesis in vivo and in vitro as well as investigated the mechanism in vitro. As the dose of glucocorticoids increased, osteoclastogenesis was stimulated at 0.1 µM, a peak was achieved at 1 µM and a corresponding decrease occurred at 10 µM. Reactive oxygen species (ROS), which play a crucial role in osteoclastogenesis, and autophagy flux activity, a cellular recycling process, were consistently up-regulated along with the dose-dependent effects of the glucocorticoids on osteoclast formation and function. N-acetyl-cysteine (NAC), a ROS scavenger, abrogated the effects of the glucocorticoids on autophagy and osteoclastogenesis. Moreover, 3-methyladenine (3-MA), an autophagy inhibitor, interrupted osteoclastogenesis stimulation by the glucocorticoids. These results implied that with glucocorticoid administration, ROS and autophagy, as a downstream factor of ROS, played vital roles in osteoclast formation and function. 3-MA administration did not enhance ROS accumulation, so that autophagy had no effect on ROS induced by glucocorticoids. Our investigation demonstrated that glucocorticoids had dose-dependent positive effects on osteoclast formation and function via ROS and autophagy. These results provide support for ROS and autophagy as therapeutic targets in glucocorticoid-related bone loss diseases such as glucocorticoid-induced osteoporosis.

Gastrodin: an ancient Chinese herbal medicine as a source for anti-osteoporosis agents via reducing reactive oxygen species.

Increased levels of reactive oxygen species (ROS) are a crucial pathogenic factor of osteoporosis. Gastrodin, isolated from the traditional Chinese herbal agent Gastrodia elata, is a potent antioxidant. We hypothesized that gastrodin demonstrates protective effects against osteoporosis by partially reducing reactive oxygen species in human bone marrow mesenchymal stem cells (hBMMSCs) and a macrophage cell line (RAW264.7 cells). We investigated gastrodin on osteogenic and adipogenic differentiation under oxidative stress in hBMMSCs. We also tested gastrodin on osteoclastic differentiation in RAW264.7 cells. Hydrogen peroxide (H2O2) was used to establish an oxidative cell injury model. Our results showed that gastrodin significantly promoted the proliferation of hBMMSCs, improved some osteogenic markers, reduced lipid generation and inhibited the mRNA expression of several adipogenic genes in hBMMSCs. Moreover, gastrodin reduced the number of osteoclasts, TRAP activity and the expression of osteoclast-specific genes in RAW264.7 cells. Gastrodin suppressed the production of reactive oxygen species in both hBMMSCs and RAW264.7 cells. In vivo, we established a murine ovariectomized (OVX) osteoporosis model. Our data revealed that gastrodin treatment reduced the activity of serum bone degradation markers, such as CTX-1 and TRAP. Importantly, it ameliorated the micro-architecture of trabecular bones. Gastrodin decreased osteoclast numbers in vivo by TRAP staining. To conclude, these results indicated that gastrodin shows protective effects against osteoporosis linking to a reduction in reactive oxygen species, suggesting that gastrodin may be useful in the prevention and treatment of osteoporosis.

Ginsenoside-Rb2 inhibits dexamethasone-induced apoptosis through promotion of GPR120 induction in bone marrow-derived mesenchymal stem cells.

Apoptosis of bone marrow-derived mesenchymal stem cells (BMMSCs) is an essential pathogenic factor of osteoporosis. Ginsenoside-Rb2 (Rb2), a 20(S)-protopanaxadiol glycoside extracted from ginseng, is a potent treatment for bone loss, which raises interest regarding the bone metabolism area. In the present study, we found that dose-response Rb2 inhibited high dosage of dexamethasone (Dex)-induced apoptosis in primary murine BMMSCs. Interestingly, Rb2 promoted GPR120 induction, which is the unsaturated long-chain fatty acid receptor. We further confirmed that GPR120-specific ShRNA reversed the inhibition of Rb2 on Dex-induced apoptosis by activating caspase-3 and reducing cell viability. In addition, Rb2 notably increased phosphorylated ERK1/2 levels and Ras kinase activity dependently through the GPR120. The ERK1/2 activity-specific inhibitor U0126 remarkably blocked the Rb2-induced antiapoptotic effect in response to Dex-induced apoptosis. Together, dose-response Rb2 protected BMMSCs against Dex-induced apoptosis dependently by inducing GPR120 promoted Ras-ERK1/2 signaling pathway. Therefore, in the prevalence of the abuse of Dex in the clinic, our findings suggest for the first time that Rb2 is not only a key to understand the link between Chinese medicine and the pathology of osteoporosis but also an underlying target for the treatment of bone complications in the foreseeable future.