ENIGMA: A Web Application for Running Online Artificial Grammar Learning Experiments.

Artificial grammar learning (AGL) is an experimental paradigm frequently adopted to investigate the unconscious and conscious learning and application of linguistic knowledge. This paper will introduce ENIGMA ( https://enigma-lang.org ) as a free, flexible, and lightweight Web-based tool for running online AGL experiments. The application is optimized for desktop and mobile devices with a user-friendly interface, which can present visual and aural stimuli and elicit judgment responses with RT measures. Without limits in time and space, ENIGMA could help collect more data from participants with diverse personal and language backgrounds and variable cognitive skills. Such data are essential to explain complex factors influencing learners' performance in AGL experiments and answer various research questions regarding L1/L2 acquisition. The introduction of the core features in ENIGMA is followed by an example study that partially replicated Chen (Lang Acquis 27(3):331-361, 2020) to illustrate possible experimental designs and examine the quality of the collected data.

The "Starting-Small" Effect in Phonology: Evidence From Biased Learning of Opaque and Transparent Vowel Harmony.

The starting-small effect is a cognitive advantage in language acquisition when learners begin by generalizing on regularities from structurally simple and shorter tokens in a skewed input distribution. Our study explored this effect as a potential explanation for the biased learning of opaque and transparent vowel harmony. In opaque vowel harmony, feature agreement occurs strictly between adjacent vowels, and an intervening "neutral vowel" blocks long-distance vowel harmony. Thus, opaque vowel harmony could be acquired even if learners start with structurally simpler and more frequent disyllabic tokens. Alternatively, transparent vowel harmony can only be observed in longer tokens demonstrating long-distance agreement by skipping a neutral vowel. Opaque vowel harmony is predicted to be learned more efficiently due to its compatibility with local dependency acquired via starting-small learning. In two artificial grammar learning experiments, learners were exposed to both vowel harmony patterns embedded in an equal number of disyllabic and trisyllabic tokens or a skewed distribution with twice as many disyllabic tokens. In Exp I, learners' test performance suggests the consistently biased learning of local and opaque vowel harmony with starting-small learning. Furthermore, in Exp II, the acquired vowel harmony patterns varied significantly by working memory capacity with a balanced but not skewed input distribution, presumably because of the ease of cognitive demand with starting-small learning.

Associations of parecoxib and other variables with recovery and safety outcomes in total knee arthroplasty: insights from a retrospective cohort study.

Background: Early mobilization post-total knee arthroplasty (TKA) significantly affects patient outcomes. While parecoxib is known to reduce postoperative pain and morphine use with a favorable safety profile, its impact on mobilization timing post-TKA remains uncertain. This retrospective study aims to assess parecoxib's influence on postoperative mobilization timing in TKA patients without compromising safety. Methods: This study included unilateral TKA patients treated for primary knee osteoarthritis under general anesthesia. We divided the study period into two intervals, 2007-2012 and 2013-2018, to evaluate temporal differences. Both the control group and parecoxib group received standard postoperative oral analgesics and as-needed intramuscular morphine. The control group did not receive parecoxib, while the parecoxib group did. Primary outcomes compared postoperative complications and mobilization timing between groups, with secondary outcomes including length of hospital stay (LOS), Visual Analog Scale (VAS) scores for pain, as-needed morphine use, and postoperative nausea/vomiting. Results: Parecoxib did not increase postoperative complications. Unmatched comparison with patients in controlled group found that patients in parecoxib group had significantly shortened mobilization time (2.2 ± 1.1 vs. 2.7 ± 1.6 days, P < 0.001) and LOS (6.7 ± 2.5 vs. 7.2 ± 2.1 days, P = 0.01). Multivariate analysis linked parecoxib use with faster mobilization (ß = -0.365, P < 0.001) but not LOS. Males showed increased mobilization time and LOS compared to females during the period of 2007-2018, but gender had no significant association with LOS during the period of 2013-2018. The 2013-2018 period saw significant reductions in both mobilization time and LOS. Use of a tourniquet and local infiltration analgesia showed no significant impact. ASA classification 1-2 was positively associated with faster mobilization but not LOS. Longer operation times were linked to delayed mobilization and increased LOS. Conclusion: In this study, intravenous parecoxib injection, female gender, and shorter OP time had consistent positive association with shorter time to mobilization after individual multivariate analysis in 2 different period. The use of parecoxib had consistent no significant association with LOS. Only shorter OP time was consistent positive associated with shorter LOS.

The Incidence of Acute Respiratory Infection Was Higher in the Older Adults with Lower Limb Fracture Who Receive Spinal Anesthesia Than Those Who Receive General Anesthesia.

INTRODUCTION: Acute respiratory infection (ARI) can significantly reduce postoperative quality of life and impair the recovery of older adult patients with lower-limb fractures, and its relationship with methods of anesthesia remains inconclusive. Using data from the National Health Insurance Research Database (NHIRD) of Taiwan, this study examined the data of patients who received surgical management for lower-limb fractures and compared those who underwent general anesthesia (GA) with those who underwent regional anesthesia (RA) in terms of their incidence of acute upper and lower respiratory infection during the one-month postoperative period. The study also identified related risk factors. MATERIAL AND METHODS: Approximately two million patients were randomly sampled from the NHIRD registry. We identified and enrolled patients with lower-limb fractures who were over 60 years old and underwent GA or RA during surgeries conducted between 2010 and 2017. We divided these patients into two groups for further analysis. The outcome of this study was the development of ARI during the one-month postoperative period. RESULTS: In total, 45,032 patients (GA group, 19,580 patients; RA group, 25,452 patients) with a mean age of 75.0 ± 8.9 years were included in our study. The incidence of postoperative ARI within one month of surgery was 8.0% (1562 patients) in the GA group and 9.5% (2412 patients) in the RA group, revealing a significant difference. The significant risk factors for the incidence of ARI were the application of RA for surgery, older age, hypertension, liver disease, and chronic obstructive pulmonary disease (COPD). A subgroup analysis revealed that the RA method was associated with a significantly higher ARI incidence relative to the GA method among patients aged between 60 and 80 years, among male patients, among the patients with or without any comorbidity and among the patients without COPD. CONCLUSION: The incidence of postoperative ARI within one month of surgery was higher among older patients with lower-limb fractures who received RA for surgery than among those who received GA for surgery. The other major risk factors for ARI were older age, hypertension, liver disease, and COPD. Therefore, we should focus on patients with a high risk of developing ARI, especially during the COVID-19 pandemic.

Survey of the triple-mentoring program for students at a religious medical school.

BACKGROUND: Tzu Chi University in Taiwan offers a unique mentoring program. This program differs from others as it comprises triple mentorship, namely, faculty mentors, Tzu Cheng/Yi De (TC/YD; senior volunteers), and school counselors. This study aimed to survey the role functions of the mentors from the perspective of medical students. METHODS: The Role Functions of the Mentoring Program Scale (RFMPS) was developed on the basis of literature reviews and focus groups and it underwent exploratory factor analysis for internal consistency and reliability. RFMPS comprises four role functions, namely, mental, educational, career, and humanistic/moral guidance counseling. The survey was distributed to 171 medical students via an online network with two-month intervals and was analyzed using multivariate analysis of variance. RESULTS: The overall response rate was 64% (116/171). The mean scores of the four role functions in descending order belonged to faculty mentors, TC/YD, and school counselors. For humanistic/moral guidance, students had an equal preference for the faculty mentors and TC/YD over school counselors. As for educational, career, and mental guidance counseling, students preferred faculty mentors over TC/YD and school counselors. Faculty mentors provided students with the required guidance counseling for all the four role functions, especially educational guidance; TC/YD in particular offered prominent humanistic/moral guidance and career counseling; school counselors were less preferred but guided students in need. CONCLUSIONS: Medical students value different role functions provided by faculty mentors, TC/YD, and school counselors. A diversified focus could be provided by the faculty mentors, particularly in educational, career, mental, and humanistic/moral counseling; TC/YD specialized in humanistic/moral guidance; and the school counselors carried out their role function only when needed. Humanistic/moral guidance is equally preferred to other types of guidance, which can be equally valuable in future mentoring programs.

Median Nerve Stimulation Facilitates the Identification of Somatotopy of the Subthalamic Nucleus in Parkinson's Disease Patients under Inhalational Anesthesia.

Deep brain stimulation (DBS) improves Parkinson's disease (PD) symptoms by suppressing neuropathological oscillations. These oscillations are also modulated by inhalational anesthetics used during DBS surgery in some patients, influencing electrode placement accuracy. We sought to evaluate a method that could avoid these effects. We recorded subthalamic nucleus (STN) neuronal firings in 11 PD patients undergoing DBS under inhalational anesthesia. Microelectrode recording (MER) during DBS was collected under median nerve stimulation (MNS) delivered at 5, 20, and 90 Hz frequencies and without MNS. We analyzed the spike firing rate and neuronal activity with power spectral density (PSD), and assessed correlations between the neuronal oscillation parameters and clinical motor outcomes. No patient experienced adverse effects during or after DBS surgery. PSD analysis revealed that peripheral 20 Hz MNS produced significant differences in the dorsal and ventral subthalamic nucleus (STN) between the beta band oscillation (16.9 ± 7.0% versus 13.5 ± 4.8%, respectively) and gamma band oscillation (56.0 ± 13.7% versus 66.3 ± 9.4%, respectively) (p < 0.05). Moreover, 20-Hz MNS entrained neural oscillation over the dorsal STN, which correlated positively with motor disabilities. MNS allowed localization of the sensorimotor STN and identified neural characteristics under inhalational anesthesia. This paradigm may help identify an alternative method to facilitate STN identification and DBS surgery under inhalational anesthesia.

Desflurane and sevoflurane differentially affect activity of the subthalamic nucleus in Parkinson's disease.

BACKGROUND: Desflurane and sevoflurane are commonly used during inhalational anaesthesia, but few studies have investigated their effects on deep cerebral neuronal activity. In addition, the association between subthalamic nucleus (STN) neurophysiology and general anaesthesia induced by volatile anaesthetics are not yet identified. This study aimed to identify differences in neurophysiological characteristics of the STN during comparable minimal alveolar concentration (MAC) desflurane and sevoflurane anaesthesia for deep brain stimulation (DBS) in patients with Parkinson's disease. METHODS: Twelve patients with similar Parkinson's disease severity received desflurane (n=6) or sevoflurane (n=6) during DBS surgery. We obtained STN spike firing using microelectrode recording at 0.5-0.6 MAC and compared firing rate, power spectral density, and coherence. RESULTS: Neuronal firing rate was lower with desflurane (47.4 [26.7] Hz) than with sevoflurane (63.9 [36.5] Hz) anaesthesia (P<0.001). Sevoflurane entrained greater gamma oscillation power than desflurane (62.9% [0.9%] vs 57.0% [1.5%], respectively; P=0.002). There was greater coherence in the theta band of the desflurane group compared with the sevoflurane group (13% vs 6%, respectively). Anaesthetic choice did not differentially influence STN mapping accuracy or the clinical outcome of DBS electrode implantation. CONCLUSIONS: Desflurane and sevoflurane produced distinct neurophysiological profiles in humans that may be associated with their analgesic and hypnotic actions.

Sevoflurane and Parkinson's Disease: Subthalamic Nucleus Neuronal Activity and Clinical Outcome of Deep Brain Stimulation.

BACKGROUND: General anesthetics-induced changes of electrical oscillations in the basal ganglia may render the identification of the stimulation targets difficult. The authors hypothesized that while sevoflurane anesthesia entrains coherent lower frequency oscillations, it does not affect the identification of the subthalamic nucleus and clinical outcome. METHODS: A cohort of 19 patients with Parkinson's disease with comparable disability underwent placement of electrodes under either sevoflurane general anesthesia (n = 10) or local anesthesia (n = 9). Microelectrode recordings during targeting were compared for neuronal spiking characteristics and oscillatory dynamics. Clinical outcomes were compared at 5-yr follow-up. RESULTS: Under sevoflurane anesthesia, subbeta frequency oscillations predominated (general vs. local anesthesia, mean ± SD; delta: 13 ± 7.3% vs. 7.8 ± 4.8%; theta: 8.4 ± 4.1% vs. 3.9 ± 1.6%; alpha: 8.1 ± 4.1% vs. 4.8 ± 1.5%; all P < 0.001). In addition, distinct dorsolateral beta and ventromedial gamma oscillations were detected in the subthalamic nucleus solely in awake surgery (mean ± SD; dorsal vs. ventral beta band power: 20.5 ± 6.6% vs. 15.4 ± 4.3%; P < 0.001). Firing properties of subthalamic neurons did not show significant difference between groups. Clinical outcomes with regard to improvement in motor and psychiatric symptoms and adverse effects were comparable for both groups. Tract numbers of microelectrode recording, active contact coordinates, and stimulation parameters were also equivalent. CONCLUSIONS: Sevoflurane general anesthesia decreased beta-frequency oscillations by inducing coherent lower frequency oscillations, comparable to the pattern seen in the scalp electroencephalogram. Nevertheless, sevoflurane-induced changes in electrical activity patterns did not reduce electrode placement accuracy and clinical effect. These observations suggest that microelectrode-guided deep brain stimulation under sevoflurane anesthesia is a feasible clinical option.

Fill the gap between traditional and new era: The medical educational reform in Taiwan.

The 7-year medical education program in Taiwan has been established since 1949. More than 60 years later, many medical professionals have observed and voiced its deficiencies following the outbreak of severe acute respiratory syndrome. The deficiencies are three-fold: (1) specialties are excessively institutionalized, (2) students engage in passive learning and memorization, and (3) passing one written national examination serves as the means of granting permanent physician qualification. The situation has aroused concerns and discussions among medical professionals and educators for a new medical education program. Authorized by the Conference of Deans of Medical Schools in Taiwan, Prof. Chyi-Her Lin assembled a team for planning medical curricular reform. Subsequently, Prof. Shan-Chwen Chang organized a task force team which has been monitoring the new 6-year program since 2013. The aims of medical reform by Prof. Lin are (1) to eliminate the specialty training part, (2) to use innovative teaching methods to motivate students to learn proactively, and (3) to implement competency-based medical education. Now, the first class of physicians will enter the workplace in 2019, subject to various clinical challenges.

Corrigendum to "Five-Year Clinical Outcomes of Local versus General Anesthesia Deep Brain Stimulation for Parkinson's Disease".

[This corrects the article DOI: 10.1155/2019/5676345.].

Over-Activated Proteasome Mediates Neuroinflammation on Acute Intracerebral Hemorrhage in Rats.

BACKGROUND: Neuroinflammation is a hallmark in intracerebral hemorrhage (ICH) that induces secondary brain injury, leading to neuronal cell death. ER stress-triggered apoptosis and proteostasis disruption caused neuroinflammation to play an important role in various neurological disorders. The consequences of ER stress and proteostasis disruption have rarely been studied during the course of ICH development. METHODS: ICH was induced by collagenase VII-S intrastriatal infusion. Animals were sacrificed at 0, 3, 6, 24, and 72 h post-ICH. Rats were determined for body weight changes, hematoma volume, and neurological deficits. Brain tissues were harvested for molecular signaling analysis either for ELISA, immunoblotting, immunoprecipitation, RT-qPCR, protein aggregation, or for histological examination. A non-selective proteasome inhibitor, MG132, was administered into the right striatum three hours prior to ICH induction. RESULTS: ICH-induced acute proteasome over-activation caused the early degradation of the endoplasmic reticulum (ER) chaperone GRP78 and IκB protein. These exacerbations were accompanied by the elevation of pro-apoptotic CCAAT-enhancer-binding protein homologous protein (CHOP) and pro-inflammatory cytokines expression via nuclear factor-kappa B (NF-κB) signal activation. Pre-treatment with proteasome inhibitor MG132 significantly ameliorated the ICH-induced ER stress/proteostasis disruption, pro-inflammatory cytokines, neuronal cells apoptosis, and neurological deficits. CONCLUSIONS: ICH induced rapid proteasome over-activation, leading to an exaggeration of the ER stress/proteostasis disruption, and neuroinflammation might be a critical event in acute ICH pathology.

An objective structured teaching exercise for faculty training and assessment of teaching ability in interprofessional collaborative practice and education.

OBJECTIVE: Improving clinical teachers' ability to teach interprofessional collaborative practice warrants development in current faculty training programs; in particular, current education training emphasizes experiential learning and multiple teaching strategies. The purpose of this study was to establish a teaching model to apply interdisciplinary collaborative care and to improve clinical teachers' execution of interprofessional practices. MATERIALS AND METHODS: Health-care faculty members were studied; this study assessed a teacher education curriculum for interprofessional education (IPE) and applied an objective structured teaching exercise (OSTE) to evaluate IPE execution by clinical teachers. RESULTS: The OSTE improved clinical teachers' IPE execution, verifying the necessity for multistrategy teaching in faculty training programs. CONCLUSIONS: This study provides different types of interprofessional faculty training and assessments. Development of an OSTE requires long-term planning, and IPE should also be incorporated into formal programs.

Promoting innovation in the objective structured teaching examination and feedback: clustering teachers to aid teaching evaluation.

PROBLEM: This study used the principles of feedback in a faculty development curriculum to enable clinical teachers to conduct objective structured teaching exercises for performance assessment. INTERVENTION: the Flanders System of Interaction Analysis (FIA) was given to analysis of the data collected from a particular situation, to videotapes of simulated clinical teaching skills. CONTEXT: The Sparse K-Means clustering method, one-way ANOVA and post hoc tests were employed to cluster the most commonly used skills by teachers and compare the features of different clusters were then discussed. OUTCOME: The evaluation method employed in this study can be extended to more teaching methods and skills. LESSONS LEARNED: that through teaching observation, clinical teaching skills and reflection teaching can be improved.

Five-Year Clinical Outcomes of Local versus General Anesthesia Deep Brain Stimulation for Parkinson's Disease.

BACKGROUND: Studies comparing long-term outcomes between general anesthesia (GA) and local anesthesia (LA) for STN-DBS in Parkinson's disease (PD) are lacking. Whether patients who received STN-DBS in GA could get the same benefit without compromising electrophysiological recording is debated. METHODS: We compared five-year outcomes for different anesthetic methods (GA vs LA) during STN-DBS for PD. Thirty-six consecutive PD patients with similar preoperative characteristics, including age, disease duration, and severity, underwent the same surgical procedures except the GA (n=22) group with inhalational anesthesia and LA (n=14) with local anesthesia during microelectrode recording and intraoperative macrostimulation test. Surgical outcome evaluations included Unified Parkinson's Disease Rating Scale (UPDRS), Mini-Mental Status Examinations, and the Beck Depression Inventory. Stimulation parameters and coordinates of STN targeting were also collected. RESULTS: Both groups attained similar benefits in UPDRS part III from STN-DBS (GA 43.2 ± 14.1% vs. LA 46.8 ± 13.8% decrease, p=0.45; DBS on/Med off vs. DBS off/Med off) and no difference in reduction of levodopa equivalent doses (GA 47.56 ± 18.98% vs. LA 51.37 ± 31.73%, p=0.51) at the five-year follow-up. In terms of amplitude, frequency, and pulse width, the stimulation parameters used for DBS were comparable, and the coordinates of preoperative targeting and postoperative electrode tip were similar between two groups. There was no difference in STN recording length as well. Significantly less number of MER tracts in GA was found (p=0.04). Adverse effects were similar in both groups. CONCLUSIONS: Our study confirmed that STN localization with microelectrode recording and patient comfort could be achieved based on equal effectiveness and safety of STN-DBS under GA compared with LA.

Magnesium sulfate inhibits binding of lipopolysaccharide to THP-1 cells by reducing expression of cluster of differentiation 14.

We investigated effects of magnesium sulfate (MgSO4) on modulating lipopolysaccharide (LPS)-macrophage binding and cluster of differentiation 14 (CD14) expression. Flow cytometry data revealed that the mean levels of LPS-macrophage binding and membrane-bound CD14 expression (mCD14) in differentiated THP-1 cells (a human monocytic cell line) treated with LPS plus MgSO4 (the LPS + M group) decreased by 28.2% and 25.3% compared with those THP-1 cells treated with LPS only (the LPS group) (P < 0.001 and P = 0.037), indicating that MgSO4 significantly inhibits LPS-macrophage binding and mCD14 expression. Notably, these effects of MgSO4 were counteracted by L-type calcium channel activation. Moreover, the mean level of soluble CD14 (sCD14; proteolytic cleavage product of CD14) in the LPS + M group was 25.6% higher than in the LPS group (P < 0.001), indicating that MgSO4 significantly enhances CD14 proteolytic cleavage. Of note, serine protease inhibition mitigated effects of MgSO4 on both decreasing mCD14 and increasing sCD14. In conclusion, MgSO4 inhibits LPS-macrophage binding through reducing CD14 expression. The mechanisms may involve antagonizing L-type calcium channels and activating serine proteases.

Medical leadership: An important and required competency for medical students.

Good medical leadership is the key to building high-quality healthcare. However, in the development of medical careers, the teaching of leadership has traditionally not equaled that of technical and academic competencies. As a result of changes in personal standards, the quality of medical leadership has led to variations between different organizations, as well as occasional catastrophic failure in the standard of care provided for patients. Leaders in the medical profession have called for reform in healthcare in response to challenges in the system and improvements in public health. Furthermore, there has been an increased drive to see leadership education for doctors starting earlier, and continuing throughout their careers so that they can take on more important leadership roles throughout the healthcare system. Being a physician requires not only management and leadership but also the need to transfer competencies to communication and critical thinking. These attributes can be obtained through experience in teamwork under the supervision of teaching staff. Therefore, medical students are expected to develop skills to deal with and resolve conflicts, learn to share leadership, prepare others to help and replace them, take mutual responsibility and discuss their performance.

Effectiveness of a training program on the role recognition and case portrayal of standardized patients.

OBJECTIVE: Standardized patient (SP) scenarios could provide medical situations of high fidelity for teaching or examinations, which would otherwise be difficult with real patients. Moreover, SPs can also be used to reliably evaluate or certify the competence of medical trainees. Since the interactions between examinee and SP are dynamic and complex, SPs need to portray the case reliably and consistently across different examinees. Thus, we developed a 1-day program for newly recruited SPs to teach basic competence in case portrayal. The purpose of this study is to assure the effectiveness of this training program in role recognition as a SP and case portrayal. MATERIALS AND METHODS: A total of 80 SPs were recruited from 2010 to 2013. They were asked to complete questionnaires before and after the training program using a five-point, Likert-type scale (1 - strongly disagree and 5 - strongly agree). The questionnaire comprised 16 items covering SP characteristics, role recognition, and case portrayal. The results were analyzed using PASW Statistics 18, paired t-test, to determine the effectiveness of the training program. RESULTS: A total of 78 questionnaires were collected for a response rate of 97.5%. The mean age of the SPs was 50.2 ± 7.9 (25-68) years. Most SPs showed improvement in role recognition. In the domain of case portrayal, three of nine items (consistency, obedience, and commitment) showed significant difference (P <0.05). CONCLUSIONS: This study suggests that this program is useful for reinforcing role recognition in newly recruited SPs. With respect to case portrayal, only consistency, obedience, and commitment were improved.

Melatonin protects brain against ischemia/reperfusion injury by attenuating endoplasmic reticulum stress.

Endoplasmic reticulum (ER) stress plays a vital role in mediating ischemic reperfusion damage in brain. In this study, we evaluated whether melatonin inhibits ER stress in cultured neurons exposed to oxygen and glucose deprivation (OGD) and in rats subjected to transient focal cerebral ischemia. Sprague-Dawley rats were treated with melatonin (5 mg/kg) or control at reperfusion onset after transient occlusion of the right middle cerebral artery (MCA) for 90 min. Brain infarction and hemorrhage within infarcts were measured. The expression of ER stress proteins of phosphorylation of PRKR­like endoplasmic reticulum kinase (p-PERK), phosphorylation of eukaryotic translation initiation factor 2α (p-eIF2α), activating transcription factor 4 (ATF4) and C/EBP homologous protein (CHOP) were detected by western blotting and immunohistochemistry analysis. The terminal deoxynucleotidyltransferase-mediated dUTP nick end labeling (TUNEL) method, cleaved caspase-3 and cytochrome c were used to investigate cell apoptosis in OGD-induced cultured neurons. Our results demonstrated that animals treated with melatonin had significantly reduced infarction volumes and individual cortical lesion sizes as well as increased numbers of surviving neurons. Melatonin can significantly modulate protein levels by decreasing both p-PERK and p-eIF2α in the ischemic core and penumbra. Moreover, the expressions of ATF4 and CHOP were restrained in the ischemic core and penumbra, respectively. Furthermore, pretreatment with melatonin at 10-100 µM effectively reduced the levels of p-PERK and p-eIF2α in cultured neurons after OGD injury. Melatonin treatment also effectively decreased neuron apoptosis resulting from OGD-induced neuron injury. These results indicate that melatonin effectively attenuated post-ischemic ER stress after ischemic stroke.

Effects of MgSO4 on inhibiting Nod-like receptor protein 3 inflammasome involve decreasing intracellular calcium.

BACKGROUND: Nod-like receptor protein 3 (NLRP3) inflammasome is a multiprotein complex composed of NLRP3, caspase-1, and apoptosis-associated speck-like protein containing a caspase recruitment domain. Activation of NLRP3 inflammasome leads to interleukin-1ß (IL-1ß) upregulation and pyroptosis, a proinflammatory cell death characterized by increased cell size. Of note, calcium signaling is crucial for NLRP3 inflammasome activation. This study elucidated the effects of magnesium sulfate (MgSO4), a potent calcium antagonist, on modulating NLRP3 inflammasome. MATERIALS AND METHODS: THP-1 cells, the human monocytic leukemia cell line, were treated with lipopolysaccharide (LPS, 1 µg/ml) plus nigericin (5 µM) (the LPS + Nig group) and LPS plus nigericin plus MgSO4 (20 mM) [the LPS + Nig + M(20)] to facilitate investigations. Levels of IL-1ß, pyroptosis, and NLRP3 inflammasome induction as well as intracellular calcium were assayed. RESULTS: IL-1ß concentration of the LPS + Nig + M(20) group was significantly lower than the LPS + Nig group (P = 0.001). Cell size of the LPS + Nig + M(20) group was significantly smaller than the LPS + Nig group (P < 0.001). Level of pyroptotic cell death of the LPS + Nig + M(20) group was significantly lower than the LPS + Nig group (P = 0.004). NLRP3 mRNA and protein concentrations of the LPS + Nig + M(20) group were also significantly lower than the LPS + Nig group (P = 0.021 and P < 0.001). Similarly, apoptosis-associated speck-like protein containing a caspase recruitment domain speck formation ratio and caspase-1 concentration of the LPS + Nig + M(20) group were significantly lower than the LPS + Nig group (both P < 0.001). The change in intracellular calcium level of the LPS + Nig + M(20) group was significantly smaller than the LPS + Nig group (P = 0.001). CONCLUSIONS: MgSO4 inhibits NLRP3 inflammasome, IL-1ß upregulation, and pyroptosis. The mechanism is consistent with decreased intracellular calcium levels.