Comparing acute normovolumic hemodilution with autologous platelet-rich plasma for blood preservation during aortic surgery : study protocol for a randomized controlled clinical trial.

BACKGROUND: Both acute normovolumic hemodilution (ANH) and autologous platelet-rich plasma (aPRP) have been demonstrated blood-protective effects in cardiac aortic surgery; however, the efficacies of the two methods have not been compared. This study aims to compare the effects of aPRP and ANH prior to aortic surgery on postoperative bleed and other outcomes. METHODS AND ANALYSIS: This is a prospective, single-center, double-blind controlled clinical trial including 160 patients randomized 1:1 to receive aPRP (test group) or autologous whole blood (ANH, control group). The primary objective is to compare the drainage volumes in the two groups at 24, 48, and 72 h postoperatively. Secondary outcomes include input of allogeneic blood and blood products and durations of aortic block, extracorporeal circulation, deep hypothermic arrest of circulation, tracheal extubation, hospital stay, requirement for secondary surgical hemostasis, and application of intra-aortic balloon pump or extracorporeal membrane oxygenation in the two groups. In addition, heart rate, systolic blood pressure, diastolic blood pressure, central venous pressure, and thromboelastography recorded before blood reservation (T1), after blood reservation (T2), before blood transfusion (T3), and after the blood is returned (T4) to the transfusion will be compared between the two groups of patients. DISCUSSION: This study will demonstrate if the use of aPRP could reduce the risk of bleeding after aortic surgery compared with ANH. The results are expected to have practical clinical applications in terms of more effective blood protection and shorter hospital stay. TRIAL REGISTRATION: This study was registered with the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/ ) with the ID ChiCTR 1900023351.Registered on May 23, 2019. TRIAL STATUS: Recruiting start date: July 1, 2019; expected recruiting end date: July 1, 2024 Version number and date: Version 2 of 05-04-2019.

Comparison of amiodarone and esmolol for prevention of reperfusion ventricular fibrillation in individuals undergoing heart valve or aortic surgery: a study protocol for a randomized controlled clinical trial.

BACKGROUND: Amiodarone and esmolol can help to prevent and treat post-cardiac surgery reperfusion ventricular fibrillation. However, the relative efficacies of these two drugs remain unknown. The aim of the current trial is to compare the performances of amiodarone and esmolol for preventing reperfusion ventricular fibrillation following open heart surgery. METHODS/DESIGN: This is a single-center, prospective, double-blind, controlled clinical trial. A total of 260 patients undergoing heart valve or aortic surgery will be assigned randomly to treatment with prophylactic esmolol (intervention group) or amiodarone (control group). The main outcome is the incidence of reperfusion ventricular fibrillation following aortic opening during extracorporeal circulation. The secondary outcomes are the rate of automatic cardiac resuscitation, energy and frequency of electrical defibrillation, number of electrical defibrillations, and pacemaker use in the two groups of patients. Information on the patients' general condition and the durations of anesthesia, extracorporeal circulation, aortic occlusion, and operation time will be recorded. We will also compare the heart rate, mean arterial pressure, and central venous pressure between the two groups of patients at induction of anesthesia (T1), start of surgery (T2), start of extracorporeal circulation (T3), aortic block (T4), aortic opening (T5), after opening for 10 (T6), 20 (T7), and 30 min (T8), at cessation of extracorporeal circulation (T9), and at the end of surgery (T10) and compare blood gas analysis results at T1, T5, T9, and T10. DISCUSSION: This study will determine if prophylactic esmolol is more effective than amiodarone for reducing the incidence of reperfusion ventricular fibrillation in patients undergoing heart valve or aortic surgery. TRIAL REGISTRATION: China Clinical Trials Registry ChiCTR1900026429. Registered on 2019.10.9.

3­N­Butyphthalide improves learning and memory in rats with vascular cognitive impairment by activating the SIRT1/BDNF pathway.

Vascular cognitive impairment (VCI) is a type of cerebral vascular disorder that leads to learning and memory decline. VCI models can be induced by chronic cerebral hypoperfusion via permanent bilateral common carotid artery occlusion. 3­N­Butylphthalide (NBP) is a neuroprotective drug used for the treatment of ischemic cerebrovascular diseases. Silent information regulator 1 (SIRT1) plays an important role in memory formation and cognitive performance, and its abnormal reduction is associated with cognitive dysfunction in neurodegenerative diseases. Brain­derived neurotrophic factor (BDNF) is a neurotrophic factor that plays critical roles in promoting neuronal growth and injury repair. The present study was performed to investigate the effects and the underlying mechanism of NBP on learning deficits in a rat model of VCI. Rats were divided into a control group, model group, low­NBP­dose group (30 mg/kg/day), high­NBP­dose group (60 mg/kg/day), NBP + SIRT1 inhibitor group and NBP + BDNF inhibitor group. Rats were then subjected to Morris water maze and T­maze tests, which identified that NBP treatment significantly attenuated memory impairments in VCI rats. Molecular examination indicated that SIRT1 and BDNF expression levels in the hippocampus were increased by NBP treatment. However, NBP failed to ameliorate cognitive function after inhibition of the SIRT1/BDNF signaling pathway. In addition, NBP in combination with a SIRT1 inhibitor suppressed BDNF protein expression, but inhibition of BDNF did not inhibit SIRT1 protein expression in rats with VCI. The present results suggested that the neuroprotective effects of NBP on learning deficits in a rat model of VCI may be via regulation of the SIRT1/BDNF signaling pathway, in which SIRT1 may be the upstream signaling molecule. Therefore, the SIRT1/BDNF pathway could be a potential therapeutic target for VCI.

Exogenous activation of cannabinoid-2 receptor modulates TLR4/MMP9 expression in a spinal cord ischemia reperfusion rat model.

BACKGROUND: Cannabinoid-2 receptor (CB2R) plays an important role in the cascading inflammation following ischemic injury. The toll-like receptors 4 (TLR4)/matrix metalloproteinase 9 (MMP9) signal pathway is involved in blood-brain barrier dysfunction induced by ischemia stroke. The aim of this study is to investigate the roles of exogenous activation of CB2R on attenuating neurological deficit and blood-spinal cord barrier (BSCB) disruption during rat spinal cord ischemia reperfusion (I/R) injury, through modulation of the TLR4/MMP9 axis. METHODS: Animals were intraperitoneally pretreated with TLR4 inhibitor TAK-242, CB2R agonist JWH-133 with or without CB2R antagonist AM630, or equivalent volume of vehicle 1 h before undergoing 14-min occlusion of descending aorta or sham operation. One, two, three, and 7 days after reperfusion, hindlimb locomotor function was evaluated with Basso, Beattie, and Bresnahan (BBB) Locomotor Scale, BSCB integrity was detected by measurement of Evans blue (EB) extravasation and spinal cord edema. The protein expression levels of CB2R, tight junction protein Zonula occluden-1 (ZO-1), TLR4, MMP9, MyD88, NF-κB p65, and NF-κB p-p65 were determined by western blot. The MMP9 activity was analyzed by gelatin zymography. Double immunofluorescence staining was used to identify the perivascular localization of CB2R, TLR4, MMP9, and reactive astrocytes, as well as the colocalization of CB2R, TLR4, and MMP9 with reactive astrocytes. RESULTS: JWH-133 pretreatment attenuated hindlimb motor functional deficit and BSCB leakage, along with preventing downregulation of ZO-1 and upregulation of TLR4/MMP9, similar to the effects of TAK-242 preconditioning. JWH-133 or TAK-242 pretreatment reduced the perivascular expression of TLR4/MMP9 and reactive astrocytes following injury. JWH-133 pretreatment also downregulated MyD88/NF-κB level, MMP9 activity, and the astrocytic TLR4/MMP9 after I/R injury. CONCLUSIONS: Exogenous activation of CB2R by JWH-133 attenuated neurological deficit and BSCB disruption after spinal cord I/R injury via inhibition of TLR4/MMP9 expression.

Dl-3n-butylphthalide improves spatial learning and memory in rats with vascular dementia by reducing autophagy via regulation of the mTOR signaling pathway.

Dl-3n-butylphthalide (NBP) has been reported to be a beneficial and promising drug for the treatment and prevention of vascular dementia (VD). NBP has been demonstrated to improve learning and memory in rats with vascular cognitive impairment by activating the silent information regulator 1/brain-derived neurotrophic factor pathway. However, NBP is a multi-target drug. Therefore, the present study aimed to determine whether the protective effects of NBP on learning deficits in a rat model of VD were due to the inhibition of autophagy via the phosphorylated mammalian target of rapamycin (p-mTOR) pathway. NBP treatment attenuated memory damage in rats with VD, as demonstrated by T-maze and Morris water maze tests. NBP administration also significantly reduced the levels of the characteristic autophagic proteins Beclin 1 and LC3II and upregulated phosphorylation levels of mTOR at Ser-2448 compared with the VD group. However, treatment of rats with VD with NBP plus the mTOR inhibitor rapamycin failed to significantly suppress Beclin 1 and LC3II expression. These results suggested that the beneficial effects of NBP on learning deficits in a rat model of VD were due to the suppression of ischemia-induced autophagy via the p-mTOR signaling pathway.

Autologous platelet-rich plasma separation technology used in the same patient receiving 2 complicated aortic surgeries within a short time period: A case report.

RATIONALE: Autologous platelet-rich plasma (PRP) separation technology has been widely used in various clinical therapies, and has achieved good results, especially in aortic surgeries. PATIENT CONCERNS: A 50-year-old man who was diagnosed with aortic dissection (Stanford B type), a thoracoabdominal aortic aneurysm, and grade 2 hypertension underwent 2 complicated aortic surgeries within 4 months. DIAGNOSES:: aortic dissection (Stanford B type). INTERVENTIONS: PRP separation used as a blood protection measure was employed in both 2 surgeries. OUTCOMES: The patient's coagulation function recovered well after the surgeries. The amount of allogeneic blood products used in the perioperation was small. LESSONS: PRP separation technology combined with blood salvage and warming of blood and fluid transfusion in the aortic surgery has been proved to be feasible and beneficial.

Effects of platelet-rich plasmapheresis during cardiovascular surgery: A meta-analysis of randomized controlled clinical trials.

OBJECTIVE: This study aimed to explore the effects of platelet-rich plasmapheresis (PRP) on the amount of postoperative blood loss and the requirements for allogeneic fresh frozen plasma (FFP) and red blood cell (RBC) transfusions during cardiovascular surgery. METHODS: A literature search of 7 online databases was conducted. Randomized control trials (RCT) comparing intraoperative PRP or appropriate control groups were considered suitable for this current study. RESULTS: Fifteen RCTs enrolling a total of 1002 patients, including 501 patients who received PRP and 501 control patients. Meta-analysis of the data from these trials showed that PRP reduced the total volume of postoperative blood loss (standardized mean difference [SMD], -0.74; 95% confidence interval [CI], -1.18 to -0.31; P < 0.05), reduced postoperative fresh frozen plasma (FFP) transfusion (SMD, -0.38; 95%CI, -0.69 to -0.08; P < 0.05), reduced postoperative RBCs transfusion (SMD, -0.44; 95%CI, -0.77 to -0.10; P < 0.05), and reduced the proportion of patients receiving postoperative allogeneic RBC transfusions (relative risk [RR], 0.44; 95%CI, 0.21-0.91, P < 0.05) during cardiovascular surgery. CONCLUSION: Conducting PRP before cardiopulmonary bypass (CPB) and transfusing autologous platelet-rich plasma (aPRP) after reversal of heparin could reduce postoperative blood loss, the requirements for blood products transfusion during cardiovascular surgery. A higher mean platelet count in aPRP may improve the final outcome. However, there was a high degree of undetermined heterogeneity among the analyzed trials, and larger and more precise RCTs are needed to confirm these conclusions.

Upregulation of TREM2 Ameliorates Neuroinflammatory Responses and Improves Cognitive Deficits Triggered by Surgical Trauma in Appswe/PS1dE9 Mice.

BACKGROUND/AIMS: TREM2 plays a crucial role in modulating microglial function through interaction with DAP12, the adapter for TREM2. Emerging evidence has demonstrated that TREM2 could suppress neuroinflammatory responses by repression of microglia-mediated cytokine production. This study investigated the potential role of TREM2 in surgery-induced cognitive deficits and neuroinflammatory responses in wild-type (WT) and APPswe/PS1dE9 mice. METHODS: Adult APPswe/PS1dE9 transgenic male mice (a classic transgenic model of Alzheimer's disease, 3 months old) and their age-matched WT mice received intracerebral lentiviral particles encoding the mouse TREM2 gene and then were subjected to partial hepatectomy at 1 month after the lentiviral particle injection. The behavioral changes were evaluated with an open-field test and Morris water maze test on postoperative days 3, 7, and 14. Hippocampal TREM2, DAP12, and interleukin (IL)-1ß were measured at each time point. Ionized calcium-binding adapter molecule 1 (Iba-1), microglial M2 phenotype marker Arg1, synaptophysin, tau hyperphosphorylation (T396), and glycogen synthase kinase-3ß (GSK-3ß) were also examined in the hippocampus. RESULTS: Surgical trauma induced an exacerbated cognitive impairment and enhanced hippocampal IL-1ß expression in the transgenic mice on postoperative days 3 and 7. A corresponding decline in the levels of TREM2 was also found on postoperative days 3, 7, and 14. Overexpression of TREM2 downregulated the levels of IL-1ß, ameliorated T396 expression, inhibited the activity of GSK-3ß, and improved sickness behavior. Increased Arg1 expression and a high level of synaptophysin were also observed in the transgenic mice following TREM2 overexpression. CONCLUSION: The downregulation of TREM2 exacerbated surgery-induced cognitive deficits and exaggerated neuroinflammatory responses in this rodent model. Overexpression of TREM2 potentially attenuated these effects by decreasing the associated production of proinflammatory cytokines, inhibiting tau hyperphosphorylation, and enhancing synaptophysin expression.

Effects of ultrasound-guided stellate-ganglion block on sleep and regional cerebral oxygen saturation in patients undergoing breast cancer surgery: a randomized, controlled, double-blinded trial.

Numerous factors could contribute to sleep disturbances in women with breast cancer. We hypothesized that stellate ganglion block (SGB) during surgery would preserve sleep after surgery and increase intraoperative regional cerebral oxygen saturation (rSO2) on the blocked side in patients undergoing breast cancer surgery. A randomized, double-blinded, controlled trial was conducted at the First Hospital of China Medical University from January 2016 to September 2016. Ninety-six patients who underwent radical breast cancer surgery requiring general anaesthesia were randomly assigned to one of two study groups: a control group that received a saline SGB and a block group that received a 0.25% ropivacaine hydrochloride SGB. The primary outcome measure was the postoperative sleep profile, which was assessed using the bispectral index on the first postoperative night. The secondary outcome measure was the intraoperative rSO2, monitored was throughout surgery using near-infrared spectroscopy. A total of 91 female patients (mean age: 45 years; range 24-51 years) were included in the study. The duration of sleep was significantly increased by 66.3 min in the ropivacaine-SGB group compared with the saline-SGB group. No differences in rSO2 were observed on either the left or right side of the patients in either group 50 min after anaesthesia induction. We conclude that ropivacaine-SGB combined with general anaesthesia might increase the first postoperative sleep duration without influencing the intraoperative rSO2 in female patients undergoing elective breast cancer surgery. Clinical trials.gov identifier NCT02651519.

Severe hemodynamic instability after indocyanine green injection during off-pump coronary artery bypass grafting: A case report.

RATIONALE: The increasingly intraoperative use of indocyanine green (ICG) means that it is necessary to be aware of both its advantages and potential adverse effects. PATIENT CONCERNS: A 76-year-old woman developed symptoms of sudden severe hemodynamic instability while undergoing coronary artery bypass grafting with ICG injection to detect the patency of the graft. The main clinical manifestations were a sudden drop in blood pressure and increased heart rate. DIAGNOSES: Severe side effects or allergic reaction of ICG. INTERVENTIONS: Cardiopulmonary bypass (CPB) was established, and an intra-aortic balloon pump was implanted in the left femoral artery after intravenous epinephrine and manual cardiac compression failed. OUTCOMES: The patient was extubated and transferred to the general ward on the third postoperative day. LESSONS: Invasive blood pressure monitoring should be carried out in patients undergoing intraoperative ICG administration. Anesthetists should pay close attention to the patient's hemodynamic fluctuations, and effective emergency measures should be implemented immediately if severe hemodynamic instability occurs.

Edaravone improves spatial memory and modulates endoplasmic reticulum stress-mediated apoptosis after abdominal surgery in mice.

Patients who receive major surgery often develop postoperative cognitive dysfunction (POCD); however, there is a lack of effective management as the pathogenesis of this disorder has not been fully elucidated. The neuroprotective effects of edaravone have been characterized in both in vitro cultured cells and in experimental animal models. The present study aimed to determine the potential role of edaravone in surgery-induced cognitive decline in mice. Animals were assigned to three groups: Control group (n=32), where mice received local anesthesia; surgery group (n=32), where mice underwent abdominal surgery under anesthesia; and edaravone group (n=32), where mice received abdominal surgery and were administered with edaravone (3 mg/kg). Morris water maze and T-maze tests demonstrated that edaravone attenuated surgery-induced cognitive impairment. Nissl staining indicated that edaravone prevented neuronal loss in the hippocampus of mice that underwent surgery. Furthermore, treatment with edaravone mitigated the surgery-induced upregulation of glucose-regulated protein 78 and CCAAT-enhancer-binding homologous protein and reduced the number of terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling-positive nuclei in mice hippocampi. In conclusion, edaravone may prevent POCD-induced neuronal apoptosis through attenuating endoplasmic reticulum stress.

Interleukin17A Promotes Postoperative Cognitive Dysfunction by Triggering ß-Amyloid Accumulation via the Transforming Growth Factor-ß (TGFß)/Smad Signaling Pathway.

Although postoperative cognitive dysfunction (POCD) is relatively common in elderly patients who have undergone major surgery, the mechanisms underlying this postoperative complication are unclear. Previously, we have investigated the role of cytokine-mediated hippocampal inflammation in the development of POCD in a rat model. Here, we sought to determine in mice the role of cytokine interleukin17A (IL17A) in POCD and to characterize the associated signaling pathways. Old mice underwent hepatectomy surgery in the presence or absence of IL17A monoclonal antibody, and cognitive function, hippocampal neuroinflammation, and pathologic markers of Alzheimer's disease (AD) were assessed. We found that the level of IL17A in the hippocampus was increased in hepatectomy mice and that cognitive impairment after surgery was associated with the appearance of certain pathological hallmarks of AD: activation of astrocytes, ß-amyloid1-42 (Aß1-42) production, upregulation of transforming growth factor-ß (TGFß), and increased phosphorylation of signaling mother against decapentaplegic peptide 3 (Smad3) protein in the hippocampus. Surgery-induced changes in cognitive dysfunction and changes in Aß1-42 and TGFß/Smad signaling were prevented by the administration of IL17A monoclonal antibody. In addition, IL17A-stimulated TGFß/Smad activation and Aß1-42 expression were reversed by IL17A receptor small interfering RNA and a TGFß receptor inhibitor in cultured astrocytes. Our findings suggest that surgery can provoke IL17A-related hippocampal damage, as characterized by activation of astrocytes and TGFß/Smad pathway dependent Aß1-42 accumulation in old subjects. These changes likely contribute to the cognitive decline seen in POCD.

miR26a modulates Th17/T reg balance in the EAE model of multiple sclerosis by targeting IL6.

A number of different microRNAs (miRNAs) have been implicated in various autoimmune diseases, including multiple sclerosis (MS). T helper (Th)17 and regulatory T cells (Tregs) have likewise been implicated as key players in MS, and a functional imbalance of these cell types is increasingly recognized as a key etiological factor in the disease. Although specific panels of transcription factors and cytokines are known to regulate the Th17/Treg balance, the role of noncoding RNAs remains poorly understood. The inflammatory cytokine, interleukin (IL)6, appears to play a critical role in both the development of the Th17 response and the inhibition of Treg functions. In this research, an IL6-associated miRNA, miR26a, was identified, and its normally downregulated expression was shown to be highly correlated with disease severity in patients suffering from MS as well as in C57BL/6 mice with experimental autoimmune encephalomyelitis (EAE; a well-established animal model of human MS). Using the EAE model system, in vivo silencing of miR26a was found to result in increased expression of Th17-related cytokines and increased severity of EAE, while overexpression of miR26a was found to result in reduced expression of Th17-related cytokines and a milder form of EAE. By contrast, Treg cell-specific transcription factor, Foxp3, was found to be positively correlated with miR26a expression. Finally, miR26a was found to downregulate Th17 and to upregulate Treg cell function through its targeting of IL6. Taken together, our data indicate an important role for miR26a in maintaining the Th17 and Treg cell balance in MS that involves repression of IL6 expression.

Vitamin D improves cognitive function and modulates Th17/T reg cell balance after hepatectomy in mice.

It is known that surgery-induced tissue damage activates the peripheral immune system resulting in the release of inflammatory mediators and cognitive impairment in aged mice. Vitamin D has been shown to have immunomodulatory function, but the molecular basis for it has not been well understood. In this study, we mainly investigated the efficacy and mechanism of vitamin D against postoperative cognitive dysfunction (POCD). The treatment of C57BL mice with vitamin D significantly preserves postoperative cognitive function, markedly inhibits surgery-induced interleukin (IL)-17, IL-6, transforming growth factor beta (TGF-ß), and retinoic acid-related orphan receptor (RORγt) production, and obviously induces IL-10 and forkhead box p3 (Foxp3) expression. These findings indicate that vitamin D amelioration of POCD is, to a large extent, due to inhibit inflammatory CD4_T cell lineage, T helper 17 (Th17) cells, accompanied with expansion in regulatory T cells (Treg cells), a subset of CD4_T cells that are important in inhibiting inflammation. Our results suggest that Th17 and Treg cell imbalance may play a role in the development of POCD. Vitamin D is useful in the control of inflammatory diseases.

Protective effects of propofol on endotoxemia-induced acute kidney injury in rats.

1. Animal studies suggest that propofol protects against endotoxaemia-induced lung and kidney injury. Upregulation of aquaporin expression in lung tissue mediates these effects, but the mechanism of action in the kidney is unclear. The present study examined the protective effects of propofol on endotoxaemia-induced acute kidney injury in rats. 2. A rat model of endotoxaemia was established using lipopolysaccharide (LPS). We determined the effects of 10% propofol administration 1 h before, during and 1 h after LPS-induced endotoxaemia on expression of aquaporin (AQP)-2, tumour necrosis factor (TNF)-α, intercellular adhesion molecule (ICAM)-1, caspase 3, Bcl-2 and Bax using reverse transcription-polymerase chain reaction, western blotting and immunocytochemistry. Renal morphology, superstructure, apoptosis and function were also assessed. 3. Normal renal tubular structure was seen in the propofol pretreated group, but LPS treatment resulted in changes to renal tissue morphology. Propofol treatment improved renal function in LPS-treated rats. Pretreatment with propofol 1 h before LPS normalized urine and serum osmolality, serum creatinine and blood urea nitrogen to control levels. Lipopolysaccharide downregulated expression of AQP-2 and downregulated the expression of ICAM-1 and TNF-α. These effects were reversed by propofol treatment. Lipopolysaccharide reduced the Bcl2 : Bax ratio and induced renal cell apoptosis and these effects were reduced by propofol treatment. Overall, propofol pretreatment had greater effects than concurrent treatment or propofol administration after LPS induction of endotoxaemia. 4. In conclusion, propofol pretreatment protected renal function in a rat model of endotoxaemia. Further studies are necessary to confirm this effect in other experimental models and in humans.

Amelioration of experimental autoimmune encephalomyelitis by ß-elemene treatment is associated with Th17 and Treg cell balance.

Experimental autoimmune encephalomyelitis (EAE), an animal mode of multiple sclerosis (MS), was previously considered that is mediated by Th1 cells. However, a number of recent studies provided strong evidence that T helper cells that produce interleukin (IL)-17 (Th17) and anti-inflammatory CD4+ Foxp3+ regulatory T cells (Tregs) play a dominant role in the pathogenesis of EAE. ß-elemene is a natural antitumor plant drug with the role of multiple target, and it has been found to pass through the blood-brain barrier easily. It also has been strongly implicated as an immune modulatory agent, but the precise mechanisms of its action are largely unknown. In the present study, we mainly investigated the efficacy and mechanism of ß-elemene against EAE in vivo and vitro. The treatment of C57 mice with ß-elemene significantly delayed the onset of EAE, markedly suppressed MOG-specific T cell proliferation in a dose-dependent manner, dramatically reduced the IL-17, IL-6, IL-23, and RORγt production and induced the Foxp3 expression in both the periphery and the inflamed spinal cord. These findings indicated that ß-elemene amelioration EAE was, to a large extent, due to inhibit differentiation and development of Th17 cells depends on down-regulating expression of IL-6, IL-23, RORγt signaling, and promoting expansion in Treg cells. Suggesting it is useful in the control of MS and other Th17 cell-mediated inflammatory diseases.