Epigenetic regulation of Kcna3-encoding Kv1.3 potassium channel by cereblon contributes to regulation of CD4+ T-cell activation.

The role of cereblon (CRBN) in T cells is not well understood. We generated mice with a deletion in Crbn and found cereblon to be an important antagonist of T-cell activation. In mice lacking CRBN, CD4(+) T cells show increased activation and IL-2 production on T-cell receptor stimulation, ultimately resulting in increased potassium flux and calcium-mediated signaling. CRBN restricts T-cell activation via epigenetic modification of Kcna3, which encodes the Kv1.3 potassium channel required for robust calcium influx in T cells. CRBN binds directly to conserved DNA elements adjacent to Kcna3 via a previously uncharacterized DNA-binding motif. Consequently, in the absence of CRBN, the expression of Kv1.3 is derepressed, resulting in increased Kv1.3 expression, potassium flux, and CD4(+) T-cell hyperactivation. In addition, experimental autoimmune encephalomyelitis in T-cell-specific Crbn-deficient mice was exacerbated by increased T-cell activation via Kv1.3. Thus, CRBN limits CD4(+) T-cell activation via epigenetic regulation of Kv1.3 expression.

Comparison between remimazolam and propofol anaesthesia for interventional neuroradiology: a randomised controlled trial.

BACKGROUND: General anaesthesia can immobile patients during interventional neuroradiology to improve image quality. Remimazolam, an ultrashort-acting benzodiazepine, is advantageous for haemodynamic stability. This study compared remimazolam and propofol anaesthesia during neuroradiology procedures regarding intraoperative hypotensive events and rapid recovery. METHODS: This single-masked randomised-controlled study included 76 participants who underwent elective endovascular embolisation in a single centre. Patients were randomised between a continuous remimazolam infusion (n = 38) or a target-controlled propofol infusion group (n = 38). In the remimazolam group, flumazenil (0.2 mg) was administered at the end of the procedure. Phenylephrine was titrated to maintain the mean arterial pressure within ± 20% of the baseline value. The primary outcome was the total phenylephrine dose during the procedure. RESULTS: The total phenylephrine dose was 0.0 [0.0-30.0] µg in the remimazolam group and 30.0 [0.0-205.0] µg in the propofol group (p = 0.001). Hypotensive events were observed in 11 (28.9%) patients in the remimazolam group and 23 (60.5%) patients in the propofol group (p = 0.001). Recovery times to spontaneous breathing, eye-opening, extubation, and orientation were shorter in the remimazolam group than in the propofol group (all p < 0.001). CONCLUSIONS: Remimazolam anaesthesia showed superior haemodynamic stability compared with propofol anaesthesia during neuroradiology procedures. Systematic use of flumazenil enabled rapid recovery from remimazolam anaesthesia. REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry; Registration number: UMIN000047384; URL: https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000054046.

Recurrent fever of unknown origin and unexplained bacteremia in a patient with a novel 4.5 Mb microdeletion in Xp11.23-p11.22.

Fever of unknown origin (FUO) remains a formidable diagnostic challenge in the field of medicine. Numerous studies suggest an association between FUO and genetic factors, including chromosomal abnormalities. Here, we report a female patient with a 4.5 Mb Xp microdeletion, who presented with recurrent FUO, bacteremia, colitis, and hematochezia. To elucidate the underlying pathogenic mechanism, we employed a comprehensive approach involving single cell RNA sequencing, T cell receptor sequencing, and flow cytometry to evaluate CD4 T cells. Analysis of peripheral blood mononuclear cells revealed augmented Th1, Th2, and Th17 cell populations, and elevated levels of proinflammatory cytokines in serum. Notably, the patient exhibited impaired Treg cell function, possibly related to deletion of genes encoding FOPX3 and WAS. Single cell analysis revealed specific expansion of cytotoxic CD4 T lymphocytes, characterized by upregulation of various signature genes associated with cytotoxicity. Moreover, interferon-stimulated genes were upregulated in the CD4 T effector memory cluster. Further genetic analysis confirmed maternal inheritance of the Xp microdeletion. The patient and her mother exhibited X chromosome-skewed inactivation, a potential protective mechanism against extensive X chromosome deletions; however, the mother exhibited complete skewing and the patient exhibited incomplete skewing (85:15), which may have contributed to emergence of immunological symptoms. In summary, this case report describes an exceptional instance of FUO stemming from an incompletely inactivated X chromosome microdeletion, thereby increasing our understanding of the genetics underpinning FUO.

Transcriptional regulation of Notch1 by nuclear factor-κB during T cell activation.

Notch1 plays important roles in T cell development and is highly expressed in activated CD4+ T cells. However, the underlying mechanism of Notch1 transcription in T cells has not been fully characterized. Therefore, we aimed to determine how Notch1 expression is regulated during the activation of CD4+ T cells. Both the surface expression and mRNA transcription of Notch1 were significantly higher in activated CD4+ T cells, but the inhibition of phosphatidylinositol 3-kinase (PI3K) by LY294002 or deletion of the Pdk1 gene impaired this upregulation of Notch1. Interrogation of the Notch1 promoter region using serially deleted Notch1 promoter reporters revealed that the - 300 to - 270 region is crucial for its transcription in activated T cells. In addition, we found that nuclear factor (NF)-κB subunits containing RelA bind directly to this promoter region, thereby upregulating transcription. In addition, inhibition of NF-κB by SN50 impaired upregulation of Notch1 surface protein and mRNA in activated CD4+ T cells. Thus, we provide evidence that Notch1 transcription in activated CD4+ T cells is upregulated via the PI3K-PDK1-NF-κB signaling pathway.

Expression of SOCS1 and SOCS3 is altered in the nasal mucosa of patients with mild and moderate/severe persistent allergic rhinitis.

BACKGROUND: The aim of this study was to evaluate the role of suppressor of cytokine signaling (SOCS) molecules, SOCS1 and SOCS3, which act as negative regulators of cytokine signaling in various allergic diseases, in patients with mild and moderate/severe persistent allergic rhinitis. METHODS: The expression and distribution pattern of SOCS1 and SOCS3 were analyzed in nasal mucosa and peripheral blood mononuclear cells (PBMC) of healthy controls, and patients with mild and moderate/severe persistent allergic rhinitis using RT-PCR, immunohistochemistry and Western blotting. IL-4, IL-13, IL-15 and IFN-γ expression was also analyzed in the nasal mucosa of each individual using RT-PCR and Western blotting. RESULTS: SOCS1 and SOCS3 mRNA and protein expression was significantly increased in the nasal mucosa and PBMC of patients with mild and moderate/severe persistent allergic rhinitis compared with healthy controls. In healthy and allergic nasal mucosa, they were commonly localized to the epithelium, submucosal glands and endothelium, showing stronger staining intensity in mild and moderate/severe persistent allergic nasal mucosa than in healthy nasal mucosa. Tissue levels of IL-4 and IL-13 were increased in moderate/severe persistent allergic nasal mucosa whereas IL-15 and IFN-γ were decreased in moderate/severe persistent allergic nasal mucosa. CONCLUSIONS: Upregulation of SOCS1 and SOCS3 in mild and moderate/severe persistent allergic rhinitis suggests that SOCS proteins may be important regulators in the pathogenesis of allergic rhinitis and play a role as molecular determinants of allergic rhinitis persistence.

Optimal headrest height for the best laryngoscopic view: by anatomical measurements.

BACKGROUND: We hypothesized that the oro-pharyngolaryngeal axes, occipito-atlanto-axial extension (OAA) angle and intubation distance would be influenced by the height of headrests. METHODS: Twenty patients were enrolled. The Macintosh 3 blade was used for direct laryngoscopy without a headrest or with the headrest of 6 or 12 cm high in randomized order, whereas a lateral radiograph of the neck was taken when the best laryngoscopic view was obtained. The following measurements were made: (1) the axis of the mouth (MA), the pharyngeal axis (PA), the laryngeal axis (LA), and the line of vision (LV). The various angles between these axes were defined: α angle between MA and PA, ß angle between PA and LA, and δ angle between LV and LA. (2) Intubation distance, (3) mentovertebral distance, and (4) OAA angle. RESULTS: Compared with 12-cm and no headrest, the δ angle decreased significantly with 6-cm headrest (19.4°/29.2°/29.2° in 6-cm/12-cm/no headrest, respectively; P < .001), and the intubation distance increased significantly (46.2/37.3/38.7 mm in 6-cm/12-cm/no headrest, respectively; P < .001). Mentovertebral distance was smallest (107.0/106.7/98.5 mm; P < .05) at 12-cm headrest. Occipito-atlanto-axial extension angle was largest significantly (40.7°/35.2°/34.5°; P < .05) at 6-cm headrest. CONCLUSION: We conclude that compared with no or 12-cm headrest, 6-cm headrest could facilitate more alignment of these axes, increase the OAA angle, and enlarge the intubation distance.

Optimal remifentanil dose for lightwand intubation without muscle relaxants in healthy patients with thiopental coadministration: a prospective randomised study.

CONTEXT: Muscle relaxants used to facilitate tracheal intubation have disadvantages. OBJECTIVE: This study was designed to evaluate the dose requirements for remifentanil combined with thiopental for optimal lightwand intubation without muscle relaxants. DESIGN: Prospective randomised controlled study. SETTING: A tertiary care teaching hospital. PATIENTS: Ninety-six patients requiring general anaesthesia for elective surgery. INTERVENTIONS: Patients received remifentanil 1, 2, or 3 µg kg(-1) (group R1, R2, R3, each n = 32) as a slow bolus infusion over 60 s, followed by thiopental 5 mg kg(-1). Ninety seconds after remifentanil administration, lightwand intubation was attempted and intubation time was recorded. Intubating conditions were considered excellent if there was no patient movement or cough, good if coughing occurred once or twice after intubation and poor if persistent movement or cough occurred after intubation. Excellent or good intubating conditions were regarded as clinically acceptable. The duration of apnoea was recorded. MAIN OUTCOME MEASURES: Intubating conditions and the duration of apnoea. RESULTS: Lightwand intubation was successful at the first attempt in all patients except for two in group R1. The intubating conditions were more acceptable in groups R2 and R3 than in group R1 (97 and 100 vs. 63%, P < 0.01). Intubation time was shorter in group R3 than in group R1 (22 ± 8 vs. 33 ± 18 s, P < 0.01). There was no significant difference in intubation time and conditions between groups R2 and R3. The mean duration of apnoea was prolonged in group R3 compared with group R2 (10.2 ± 2.1 vs. 4.6 ± 1.6 min, P < 0.01). CONCLUSION: Our results suggest that remifentanil 2 or 3 µg kg(-1) combined with thiopental 5 mg kg provides acceptable conditions for lightwand intubation without muscle relaxants. Spontaneous ventilation returns more rapidly following remifentanil 2 µg kg(-1) than with remifentanil 3 µg kg(-1).

Feasibility of continuous glucose monitoring in critically ill emergency department patients.

BACKGROUND: Glucose control is important in the management of critically ill patients. However, strict glucose control requires a large amount of nursing resources, especially in overcrowded emergency departments (EDs). OBJECTIVES: A continuous glucose monitoring system (CGMS) may be beneficial for glucose control in the ED. The objective of this study was to determine the test characteristics of CGMS in critically ill ED patients. METHODS: A prospective observational study of critically ill ED patients was conducted. During a patient's visit to the ED, a CGMS sensor measured their interstitial fluid glucose levels continuously. Capillary glucose was measured every hour and used for glucose control and as a reference value. CGMS values were recorded in real time and compared with capillary glucose values. RESULTS: A total of 122 pairs of capillary and CGMS glucose values in 12 patients were analyzed. The correlation coefficient was 0.87, and Bland-Altman analysis showed that 117 pairs (95.9%) were within a 95% confidence interval. A Clarke Error Grid Analysis indicated an overall accuracy of 96.8% (Zones A and B). However, the mean absolute relative difference (MARD) was significantly higher in the hypoglycemic range than in a normo- or hyperglycemic range (p = 0.001). The sensitivity and positive predictive value of CGMS for detecting hypoglycemia were 33.3% and 16.7%, respectively. The CGMS specificity and negative predictive value were 95.8% and 98.3%, respectively. There was no linear correlation between MARD and body mass index, axillary temperature, inotrope score, and base deficit (all p-value >0.05). CONCLUSION: CGMS demonstrated good clinical accuracy by Clarke Error Grid Analysis. There also was high agreement between CGMS and capillary glucose levels. However, CGMS demonstrated only limited real-time hypoglycemia detection ability in critically ill ED patients.

The 90° rotation technique improves the ease of insertion of the ProSeal™ laryngeal mask airway in children.

BACKGROUND: A previous study using a 180° rotation to insert the ProSeal™ laryngeal mask airway (LMA ProSeal) in children did not show improvement over the standard technique. We used a 90° rotation technique to insert the LMA ProSeal in pediatric patients and compared ease of insertion and pharyngeal trauma with the standard technique. METHODS: This prospective randomized controlled study included 126 patients aged three to nine years. Anesthesia was induced with thiopental and rocuronium, and the LMA ProSeal used in the study ranged in size from 2 to 3 depending on the patient's body weight. In the control group (n = 63), the LMA ProSeal was inserted using the index finger. In the rotation group (n = 63), the entire cuff of the LMA ProSeal was placed in the patient's mouth without finger insertion and rotated 90° counter clockwise around the tongue. The LMA ProSeal was then advanced and rotated back until resistance was felt. The primary outcome was the insertion success rate at first attempt. RESULTS: The success rate of insertion at first attempt was higher with the rotation technique than with the standard technique (97% vs 70%, respectively; P < 0.001) and the insertion time was shorter (16 ± 6 sec vs 30 ± 24 sec, respectively; P < 0.001). Mean blood pressure after LMA ProSeal insertion increased significantly in the control group (62 ± 12 to 69 ± 17 mmHg; P = 0.01), but not in the rotation group. The incidence of blood staining was lower in the rotation group than in the control group (10% vs 25%, respectively; P = 0.03), but the incidence of sore throat was not significantly different (24% vs 22%, respectively; P = 0.9). CONCLUSIONS: The 90° rotation technique improves ease of insertion of the LMA ProSeal in children, and it decreases the risk of pharyngeal trauma. (ClinicalTrials.gov number, NCT01076725).

A preemptive alveolar recruitment strategy before one-lung ventilation improves arterial oxygenation in patients undergoing thoracic surgery: a prospective randomised study.

BACKGROUND AND OBJECTIVE: Arterial hypoxaemia remains a problem during one-lung ventilation (OLV). We determined whether a preemptive alveolar recruitment strategy (ARS) before OLV improves arterial oxygenation during OLV in patients undergoing thoracic surgery. METHODS: Forty-two patients were allocated randomly to receive either a tidal volume of 10 ml kg(-1) (group C) or ARS of 10 manual breaths with a peak inspiratory pressure of 40 cmH2O followed by positive end-expiratory pressure (PEEP) of 15 cmH2O until OLV commenced (group P). The dependent lung was ventilated with a tidal volume of 6 ml kg(-1) and PEEP of 5 cmH2O during OLV in both groups. Arterial blood gas data were recorded before ARS (baseline), after 15, 30, 45, 60 min of OLV, and at the end of OLV. RESULTS: Baseline paO2 in group P was similar to that in group C (29.9 +/- 3.9 vs. 30.0 +/- 3.5 kPa). However, paO2 was significantly higher in group P than in group C during OLV (38.9 +/- 15.0 vs. 28.8 +/- 14.4 kPa after 15 min of OLV, 39.6 +/- 13.3 vs. 31.2 +/- 13.9 kPa after 60 min of OLV and 45.5 +/- 12.1 vs. 34.3 +/- 12.0 kPa before an air leakage test, P < 0.05). The alveolar-arterial oxygen gradient was significantly lower in group P than in group C after 15 min of OLV and at the end of OLV (46.1 +/- 14.4 vs. 55.9 +/- 14.7, 39.7 +/- 12.4 vs. 50.7 +/- 12.3 kPa, P < 0.05). CONCLUSION: Preemptive ARS before OLV is effective in improving arterial oxygenation during the entire period of OLV.

A double bending lightwand can provide more successful endotracheal intubation in patients with a short thyromental distance: a prospective randomised study.

BACKGROUND AND OBJECTIVE: This study assessed the efficacy of endotracheal intubation using a double bending lightwand in patients with an anticipated difficult airway because of a short thyromental distance. METHODS: On the basis of the shape of the lightwand used, 68 patients with a thyromental distance of less than 65 mm undergoing general anaesthesia were randomly allocated to one of two groups. In the conventional bending group (n = 34), the lightwand was bent at 6.5 cm from the distal end to 90° angle. In the double bending group (n = 34), the lightwand was bent 30° at 15 cm from its tip in addition to the conventional bending. The ease of insertion was assessed by the lightwand search time and success rate at the first attempt. Post-operative complications, if any, were noted. RESULTS: The success rate of intubation at the first attempt was higher for the double bending group (94 vs. 74%, P < 0.05). The search time was significantly shorter in the double bending group than the conventional bending group (10 ± 6 vs. 15 ± 8 s, P < 0.01). Mean blood pressure and heart rate increased after intubation in both groups (P < 0.05), but there were no significant differences between the groups. The incidence of post-operative sore throat and mucosal bleeding was not significantly different between the groups. CONCLUSION: We conclude that the double bending lightwand is associated with a greater success rate of intubation in patients with an anticipated difficult airway because of a short thyromental distance.

Direct One-Step Growth of Bimetallic Ni2Mo3N on Ni Foam as an Efficient Oxygen Evolution Electrocatalyst.

A simple and economical synthetic route for direct one-step growth of bimetallic Ni2Mo3N nanoparticles on Ni foam substrate (Ni2Mo3N/NF) and its catalytic performance during an oxygen evolution reaction (OER) are reported. The Ni2Mo3N/NF catalyst was obtained by annealing a mixture of a Mo precursor, Ni foam, and urea at 600 °C under N2 flow using one-pot synthesis. Moreover, the Ni2Mo3N/NF exhibited high OER activity with low overpotential values (336.38 mV at 50 mA cm-2 and 392.49 mV at 100 mA cm-2) and good stability for 5 h in Fe-purified alkaline electrolyte. The Ni2Mo3N nanoparticle surfaces converted into amorphous surface oxide species during the OER, which might be attributed to the OER activity.

ZIP8 exacerbates collagen-induced arthritis by increasing pathogenic T cell responses.

Zinc is a trace element that is essential for immune responses. Therefore, changes in cellular zinc levels in specific immune cells may influence inflammatory autoimmune diseases, such as rheumatoid arthritis (RA). However, the regulation of zinc mobilization in immune cells and its role in the pathogenesis of RA are not fully understood. Thus, we investigated the roles of zinc transporters in RA pathogenesis. We demonstrated that ZIP8 was specifically upregulated in CD4+ T cells that infiltrated the inflamed joint and that ZIP8 deficiency in CD4+ T cells abrogated collagen-induced arthritis. ZIP8 deficiency dramatically affected zinc influx in effector T cells and profoundly reduced T cell receptor (TCR)-mediated signaling, including NF-κB and MAPK signaling, which are pathways that are involved in T helper (Th) 17 cell differentiation. Taken together, our findings suggest that ZIP8 depletion in CD4+ T cells attenuates TCR signaling due to insufficient cellular zinc, thereby reducing the function of effector CD4+ T cells, including Th17 cells. Our results also suggest that targeting ZIP8 may be a useful strategy to inhibit RA development and pathogenesis.

A comparison of direct laryngoscopic views depending on pillow height.

PURPOSE: This study was conducted to determine the optimal pillow height for the best laryngoscopic view. METHODS: Fifty patients were enrolled and preanesthetic airway evaluations were recorded. After induction of anesthesia, the Macintosh 3 blade was used for direct laryngoscopy without a pillow or with a pillow 3, 6, or 9 cm high in randomized order while the laryngeal view was imaged continuously on a monitor of the integrated video system. The best direct laryngoscopic view was sought for in each condition and graded by one anesthesiologist. The correlations between the preanesthetic airway assessments and the pillow height providing the best laryngoscopic view were analyzed. RESULTS: The laryngoscopic view with the 9-cm pillow was significantly superior to that with other pillows and without a pillow (P < 0.001). The incidence of difficult laryngoscopy (Cormack and Lehane grade 3) was 16% without a pillow. In these cases, laryngoscopic views were improved with a 9-cm pillow. In five patients with a short neck (<15 cm), better laryngoscopic view was observed with a 3- or 6-cm pillow compared with the 9-cm pillow. Neck length had a significant correlation (rho = 0.326, P = 0.027) with the pillow height providing the best laryngoscopic views. CONCLUSION: We recommend the use of a 9-cm pillow during direct laryngoscopy in the sniffing position. In contrast, pillows <9 cm appear to be advantageous in short-necked patients.

High-throughput epitope profiling of antibodies in the plasma of Alzheimer's disease patients using random peptide microarrays.

The symptoms of Alzheimer's disease (AD), a major cause of dementia in older adults, are linked directly with neuronal cell death, which is thought to be due to aberrant neuronal inflammation. Autoantibodies formed during neuronal inflammation show excellent stability in blood; therefore, they may be convenient blood-based diagnostic markers of AD. Here, we performed microarray analysis of 29,240 unbiased random peptides to be used for comprehensive screening of AD-specific IgG and IgM antibodies in the blood. The results showed that (1) sequence-specific and isotype-specific antibodies are regulated differentially in AD, and combinations of these antibodies showing high area under the receiver operating characteristic curve values (0.862-0.961) can be used to classify AD, (2) AD-specific IgG antibodies arise from IgM antibody-secreting cells that existed before disease onset and (3) target protein profiling of the antibodies identified some AD-related proteins, some of which are involved in AD-related signalling pathways. Therefore, we propose that these epitopes may facilitate the development of biomarkers for AD diagnosis and form the basis for a mechanistic study related to AD progression.

BATF regulates collagen-induced arthritis by regulating T helper cell differentiation.

BACKGROUND: We recently demonstrated that BATF, a member of the activator protein-1 (AP-1) family, regulates osteoarthritic cartilage destruction. Here, we explored the roles and regulatory mechanisms of BATF in collagen-induced arthritis (CIA) in mice. METHODS: CIA and K/BxN serum transfer were used to generate inflammatory arthritis models in wild-type (WT) and Batf-/- mice. RA manifestations were determined by examining CIA incidence, clinical score, synovitis, synovial hyperplasia, angiogenesis in inflamed synovium, pannus formation, bone erosion, and cartilage destruction. Immune features in RA were analyzed by examining immune cell populations and cytokine production. RESULTS: BATF was upregulated in the synovial tissues of joints in which inflammatory arthritis had been caused by CIA or K/BxN serum transfer. The increases in CIA incidence, clinical score, and autoantibody production in CIA-induced WT mice were completely abrogated in the corresponding Batf-/- DBA/1 J mice. Genetic ablation of Batf also inhibited CIA-induced synovitis, synovial hyperplasia, angiogenesis in synovial tissues, pannus formation, bone erosion, and cartilage destruction. Batf knockout inhibited the differentiation of T helper (Th)17 cells and the conversion of CD4+Foxp3+ cells to CD4+IL-17+ cells. However, BATF did not modulate the functions of fibroblast-like synoviocytes (FLS), including the expressions of chemokines, matrix-degrading enzymes, vascular endothelial growth factor, and receptor activator of NF-κB ligand (RANKL). CONCLUSION: Our findings indicate that BATF crucially mediates CIA by regulating Th cell differentiation without directly affecting the functions of FLS.

Perioperative lung-protective ventilation strategy reduces postoperative pulmonary complications in patients undergoing thoracic and major abdominal surgery.

The occurrence of postoperative pulmonary complications is strongly associated with increased hospital mortality and prolonged postoperative hospital stays. Although protective lung ventilation is commonly used in the intensive care unit, low tidal volume ventilation in the operating room is not a routine strategy. Low tidal volume ventilation, moderate positive end-expiratory pressure, and repeated recruitment maneuvers, particularly for high-risk patients undergoing major abdominal surgery, can reduce postoperative pulmonary complications. Facilitating perioperative bundle care by combining prophylactic and postoperative positive-pressure ventilation with intraoperative lung-protective ventilation may be helpful to reduce postoperative pulmonary complications.

Myeloid-Derived Suppressor Cells Are Controlled by Regulatory T Cells via TGF-ß during Murine Colitis.

Myeloid-derived suppressor cells (MDSCs) are well known regulators of regulatory T cells (Treg cells); however, the direct regulation of MDSCs by Treg cells has not been well characterized. We find that colitis caused by functional deficiency of Treg cells leads to altered expansion and reduced function of MDSCs. During differentiation of MDSCs in vitro from bone marrow cells, Treg cells enhanced MDSC function and controlled their differentiation through a mechanism involving transforming growth factor-ß (TGF-ß). TGF-ß-deficient Treg cells were not able to regulate MDSC function in an experimentally induced model of colitis. Finally, we evaluated the therapeutic effect of TGF-ß-mediated in-vitro-differentiated MDSCs on colitis. Adoptive transfer of MDSCs that differentiated with TGF-ß led to better colitis prevention than the transfer of MDSCs that differentiated without TGF-ß. Our results demonstrate an interaction between Treg cells and MDSCs that contributes to the regulation of MDSC proliferation and the acquisition of immunosuppressive functions.

Effect of coenzyme Q10 on spinal cord ischemia-reperfusion injury.

OBJECT: Spinal cord ischemia remains a serious complication of thoracoabdominal aortic aneurysm surgery. Coenzyme Q10, a potent antioxidant, has been reported to exert a neuroprotective effect. In the present study, we evaluated the effect of coenzyme Q10 pretreatment on spinal cord ischemia-reperfusion injury. METHODS: Male Sprague-Dawley rats were treated with either 300 mg/kg coenzyme Q10 (CoQ10 group, n = 12) or saline (control and sham groups, n = 12 for each group) for 5 days before ischemia. Spinal cord ischemia was induced in the control and CoQ10 groups. Neurological function was assessed using the Basso-Beattie-Bresnahan (BBB) motor rating scale until 7 days after reperfusion, and then the spinal cord was harvested for histopathological examinations and an evaluation of malondialdehyde level. RESULTS: On post-reperfusion Day 1, the CoQ10 group showed higher BBB scores compared with those in the control group, although the difference was not significant. However, on Day 2, the CoQ10 group showed a significantly higher BBB score than the control group (14.0 [10.3-15.0] vs 8.0 [5.0-9.8], median [IQR], respectively; p = 0.021), and this trend was maintained until Day 7 (17.5 [16.0-18.0] vs 9.0 [6.5-12.8], respectively; p < 0.001). Compared with the control group, the CoQ10 group had more normal motor neurons (p = 0.003), fewer apoptotic changes (p = 0.003) and a lower level of tissue malondialdehyde (p = 0.024). CONCLUSIONS: Pretreatment with 300 mg/kg coenzyme Q10 resulted in significantly improved neurological function and preservation of more normal motor neurons.