White matter hyperintensity, parent artery steno-occlusion, and neurological deterioration in anterior circulation single subcortical infarction patients.

BACKGROUND: The evidence for the association between white matter hyperintensity (WMH) severity and neurological deterioration (ND) in patients with single subcortical infarction (SSI) remains unclear and whether the association between them is modified by anterior circulation parent artery steno-occlusion (PAS) is unknown. Herein, we aimed to prospectively investigate the internal relevance. METHODS: In this prospective study, the severity of WMH and PAS were assessed in 288 consecutive patients with anterior circulation SSI arriving at our hospital, a tertiary teaching hospital affiliated with Fudan University, 24 h after onset from January 2017 to December 2018. The multivariable logistic regression model was used to estimate the association between WMH severity and the risk of ND within 7 days after stroke onset as well as the interactive effect between WMH severity and PAS on ND among patients with SSI. RESULTS: PAS modified the association between WMH severity and ND among patients with SSI (pinteraction = .029). After multivariate adjustment, the odds ratios of moderate-severe WMH associated with ND were 1.61 (95% CI, 0.50-5.19; ptrend = .428) for patients with PAS, and 0.37 (95% CI, 0.14-0.97; ptrend = .043) for those without PAS. Adding WMH severity to conventional risk factors improved risk prediction for ND in patients without PAS (net reclassification improvement: 48.2%, p = .005; integrated discrimination index: 2.5%, p = .004) but not in those with PAS. CONCLUSION: There was a modified effect of PAS on the association between WMH severity and ND within 7 days after stroke onset among patients with anterior circulation SSI, which deserves more research attention. WMH was negatively associated with ND in anterior circulation SSI patients without PAS.

Prediction of poststroke cognitive impairment based on the systemic inflammatory response index.

BACKGROUND: Poststroke cognitive impairment (PSCI) is a prevalent complication among stroke survivors. Although the systemic inflammatory response index (SIRI) has been shown to be a reliable predictor of a variety of inflammatory diseases, the association between the SIRI and PSCI is still unclear. Therefore, the purpose of this study was to investigate the relationship between SIRI and PSCI, and to design a nomogram to predict the risk of PSCI in acute ischemic stroke (AIS) patients. METHODS: A total of 1342 patients with AIS were included in the study. Using the Mini-Mental State Examination scale, patients were separated into PSCI and non-PSCI groups within 2 weeks of stroke. Clinical data and SIRI values were compared between the groups. We developed the optimal nomogram for predicting PSCI using multivariate logistic regression. Finally, the nomogram was validated using the receiver operating characteristic curve, calibration curve, and decision curve analysis (DCA). RESULTS: In total, 690 (51.4%) patients were diagnosed with PSCI. After adjusting for potential confounders, the SIRI (OR = 1.226, OR: 1.095-1.373, p < .001) was shown to be an independent risk factor for PSCI in the logistic regression analysis. The nomogram based on patient gender, age, admission National Institutes of Health Stroke Scale scores, education, diabetes mellitus, and SIRI had good discriminative ability with an area under the curve (AUC) of 0.716. The calibration curve and Hosmer-Lemeshow test revealed excellent predictive accuracy for the nomogram. Finally, the DCA showed the good clinical utility of the model. CONCLUSION: Increased SIRI on admission is correlated with PSCI, and the nomogram built with SIRI as one of the predictors can help identify PSCI early.

Value of the stroke 1-2-0 prehospital stroke education system: the experience of a general practitioner team.

BACKGROUND: Stroke is one of the leading causes of death worldwide, especially in developing countries. In China, there is an urgent need to educate people about stroke awareness and the importance of using emergency medical services (EMS) quickly after a stroke has occurred. OBJECTIVE: We sought to explore the effects of the Stroke 1-2-0 Prehospital Stroke Education System based on the experience of a general practitioner team. METHOD: We prospectively enrolled 119 community general practitioners to be trained in the procedures advocated by the Stroke 1-2-0 Prehospital Stroke Education System. The training content included early detection of ischemic stroke, first aid for stroke, and intravenous thrombolysis; The effects of the training were later evaluated via a before-and-after comparison. The 119 enrolled physicians formed a Stroke 1-2-0 lecturer group and taught stroke knowledge to community residents. The group remained active for 6 months, during which the medical treatment data of stroke patients (i.e., stroke onset time, prehospital delay, whether an ambulance was called, and whether thrombolytic therapy was performed) in each of 5 jurisdictions were recorded for the month before (January 2021) and that after (August 2021) the 6-month community education program. Finally, the effects of the community education program were evaluated. RESULTS: The participants' understanding of intravenous thrombolysis in the treatment of acute ischemic stroke improved significantly after the training as compared with their earlier understanding (96% vs. 78.99%; P < .001), and their understanding of the time window for intravenous thrombolysis increased from 26.05% before to 72% (P < .001) after the training. Most of the participants (90% vs. 67.23%; P < .001) said that they would immediately call the 120 emergency number of China's emergency phone system if they encountered individuals who appeared to be victims of acute stroke. A total of 82 stroke patients were seen before and 67 after the community education program. As for the use of the emergency call system, more patients with stroke activated that system after the program versus before (21.95% vs. 37.31%; P = .04). The 3-hour arrival rate after the program was nearly three times higher than that before the program (62.69% vs. 19.51%; P < .001). Also, regarding receiving thrombolysis after the occurrence of a stroke, the program triggered a substantial increase compared with the total earlier (19.4% vs. 6.1%; P = .013). CONCLUSION: We found that the Stroke 1-2-0 Prehospital Stroke Education System significantly improved community residents' knowledge regarding stroke.

Early antithrombotic therapy in patients with postinterventional cerebral hyperdensity reduces early neurological deterioration after mechanical thrombectomy.

BACKGROUND: Initiation of early antithrombotic therapy after acute ischemic stroke (AIS) is crucial. We aimed to investigate whether early antithrombotic therapy influences early neurological deterioration (END) in AIS patients with postinterventional cerebral hyperdensity (PCHD) immediately after mechanical thrombectomy (MT). METHODS: We retrospectively analyzed 108 consecutive anterior circulation AIS patients with PCHD immediately after MT. All patients were divided into END group and non-END group and END was defined as an increase of four points or more on the postinterventional National Institutes of Health Stroke Scale (NIHSS) score within the first 72 h after MT. Early antithrombotic therapy was defined as patients with PCHD who received antithrombotic therapy within 24 h after MT. Statistical analyses were performed to evaluate the association between early antithrombotic therapy and the risk of END. RESULTS: Among 108 patients, 27 (25%) patients developed END. Multivariate regression analysis revealed that early use of antithrombotic therapy (OR = 0.229, 95%CI = 0.083-0.626, P = 0.004) was an independent protector of END and postinterventional low density shadow exceeding 1/3 of the vascular territory (OR = 4.000, 95%CI = 1.157-13.834, P = 0.029) was an independent risk factor for END. CONCLUSION: Antithrombotic therapy within 24 h after MT maybe associated with the reduced risk of END in anterior circulation AIS patients with PCHD.

Systemic inflammation response index predicts 3-month outcome in patients with mild acute ischemic stroke receiving intravenous thrombolysis.

Introduction: A crucial aspect of stroke progression is the inflammatory response. As novel inflammatory and prognostic markers, the systemic immune inflammation index (SII) and the systemic inflammation response index (SIRI) have recently been studied. The objective of our study was to evaluate the prognostic value of SII and SIRI in mild acute ischemic stroke (AIS) patients following intravenous thrombolysis (IVT). Methods: Our study screened the clinical data of patients with mild AIS admitted to the Minhang Hospital of Fudan University for retrospective analysis. The SIRI and SII were examined by the emergency laboratory before IVT. Functional outcome was evaluated 3 months after the onset of stroke using the modified Rankin Scale (mRS). mRS ≥ 2 was defined as an unfavorable outcome. The relationship between SIRI and SII and the 3-month prognosis was determined using both univariate and multivariate analysis. Receiver operating characteristic curve was performed to evaluate the predictive value of SIRI for AIS prognosis. Results: A total of 240 patients were included in this study. Both SIRI and SII were higher in the unfavorable outcome group than in the favorable outcome group [1.28 (0.70-1.88) vs. 0.79 (0.51-1.08), P < 0.001 and 531.93 (377.55-797.12) vs. 397.23 (263.32-577.65), P < 0.001]. Multivariate logistic regression analyses showed that SIRI was significantly associated with 3-month unfavorable outcome of mild AIS patients [odds ratio (OR) = 2.938, 95% confidence interval (CI) = 1.805-4.782, P < 0.001], conversely, SII had no prognostic value. When SIRI combined with the established clinical factors, the area under the curve (AUC) showed a significant improvement (0.773 vs. 0.683, P for comparison = 0.0017). Conclusions: Higher SIRI could be valuable in predicting poor clinical outcomes for patients with mild AIS following IVT.

Risk factors for small intestinal bacterial overgrowth in patients with acute ischaemic stroke.

Introduction. The intestinal flora has become a promising new target in acute ischaemic stroke (AIS), and small intestinal bacterial overgrowth (SIBO) is a common pathological condition of the intestinal flora. Recently, the lactose hydrogen-methane breath test has emerged as a non-invasive and economical method for the detection of SIBO in AIS patients. Exploring the prevalence of SIBO and its associated risk factors will provide a clinical basis for the association between intestinal flora and AIS.Hypothesis/Gap Statement. Given that the prevalence of SIBO and its risk factors in patients with AIS remain to be studied, there is a need to investigate them.Aim. This study aimed to investigate the prevalence and risk factors of SIBO in patients with AISMethodology. Eighty patients tested for SIBO using the lactulose hydrogen-methane breath test were evaluated. Patients were divided into SIBO-positive and SIBO-negative groups according to the presence or absence of SIBO, respectively. The baseline characteristics and clinical biochemical indicators of the patients were compared between the two groups. The independent risk factors and predictive value of SIBO in AIS patients were determined using multivariate logistic regression and receiver operating characteristic (ROC) curve analyses.Results. Of the 80 consecutive patients with AIS, 23 (28.8 %) tested positive for SIBO. Triglyceride (TG) and homocysteine (Hcy) levels were identified as independent risk factors for SIBO in patients with AIS using multivariate logistic regression analysis (P<0.005). ROC curve analysis showed that the area under the curve (AUC) of TG was 0.690 (95 % CI 0.577-0.789, P=0.002). The sensitivity, specificity and optimal cut-off values were 95.7 %, 35.1 % and 1.14 mmol l-1, respectively. The AUC of Hcy was 0.676 (95 % CI 0.562-0.776, P=0.01). The sensitivity, specificity and optimal cut-off values were 73.9 %, 59.7 % and 14.1 µmol-1, respectively. When TG and Hcy levels were combined, the AUC increased to 0.764 (95 % CI 0.656-0.852, P<0.001). The specificity and sensitivity were 61.4 and 82.6 %, respectively. This showed that the combined detection of TG and Hcy levels had a higher predictive valueConclusion. The prevalence of SIBO in patients with AIS was 28.8 %. TG and Hcy levels are independent risk factors for SIBO in patients with AIS. Both markers had good predictive value for the occurrence of SIBO. In the future, we should actively utilize these indicators to prevent intestinal flora imbalance and the occurrence of SIBO.

Safety and efficacy of a new modified intravenous recombinant tissue plasminogen activator (rt-PA) regimen in Chinese patients with acute ischemic stroke: A descriptive retrospective cohort study with subgroup-analysis of different rt-PA dose.

Evidence for effects of the dose of recombinant tissue plasminogen activator(rt-PA) in Asian populations is inconclusive. The standard dose may cause drug waste and increase economic burden in developing country. Therefore, we preliminarily describe the safety and efficacy of a new modified dose of rt-PA regimen(0.6 or 0.9 mg/kg, with a maximum dose of 50 mg) in real world settings. 265 consecutive patients with ischemic stroke were treated with intravenous(IV) rt-PA alone from all the 323 consecutive patients treated with reperfusion therapy between January 1, 2017 and March 31, 2020. Safety and Efficacy was assessed by early neurological improvement(ENI), early neurological deterioration(END), symptomatic intracranial hemorrhage(sICH) and 90-day outcome defined by modified Rankin scale(mRS). Subgroup analysis was conducted to draw comparisons between different dose groups ([0.5,0.6)mg/kg, [0.6,0.7)mg/kg, [0.7,0.8)mg/kg, [0.8,0.9]mg/kg). Among the 265 patients, 150(56.60%) had a favorable outcome at 3 months(3 M); Mortality occurred in 17(6.40%) in 3 M; sICH in 12(4.50%); ENI in 70(26.40%); END2 in 29(10.90%) and END4 in 18(6.80%). In subgroup analysis, there was a significant difference in sICH that more patients developed sICH in [0.8-0.9]mg/kg group(P = 0.044) in univariate analysis of different dose. After adjusting, there was no significant difference between 4 dosage groups. Significant differences were seen in gender, atrial fibrillation and baseline NIHSS in the multivariable model of favorable outcome at 3 M. Our study preliminarily shows a good safety and efficacy of our modified rt-PA regimen, indicating that this regimen should be worthy of further study especially in developing country to reduce the financial burden of patients and avoid drug waste.

Effects of suspended particulate matter from natural lakes in conjunction with coagulation to tetracycline removal from water.

Coagulation is a common method used to remove suspended particulate matter (SPM) from the water supply. SPM has preferable adsorption ability for antibiotics in water; therefore, SPM adsorption and coagulation may be a possible way to remove tetracycline (TC) from water. This study carried out coagulation experiments combining SPM collected from a natural lake at a location with three common coagulants-polyaluminum sulfate, polyaluminum chloride, and polyferric sulfate-under different pH values, exploring the adsorption of TC by SPM, coagulation of SPM with TC, and the primary influencing factors of this process. The maximum removal rate of TC can reach 97.87% with an SPM concentration of 1000 mg/L. Multi-factor analysis of variance showed the importance of various TC removal factors, which were ranked as follows: SPM concentration â‰« initial TC concentration > type of coagulant > pH values. The higher the SPM concentration, the better the TC removal (p < 0.001). Fourier infrared spectroscopy results demonstrated the strong adsorption effect of SPM on TC after being combined with a coagulant, and scanning electron microscopy also indicated that SPM becomes effective nuclei in the coagulation process, which is a possible reason for better TC removal. However, the effluent turbidities under 1000 mg/L SPM concentrations were high without coagulant aid. With the addition of coagulant aid anion polyacrylamide, the TC removal remained unchanged, effluent turbidity significantly reduced, and the TC desorption became low. These results indicate that applying SPM from natural lakes in the coagulation process could potentially remove TC in water.

Change and predictive ability of circulating immunoregulatory lymphocytes in long-term outcomes of acute ischemic stroke.

Lymphocytes play an important role in the immune response after stroke. However, our knowledge of the circulating lymphocytes in ischemic stroke is limited. Herein, we collected the blood samples of clinical ischemic stroke patients to detect the change of lymphocytes from admission to 3 months after ischemic stroke by flow cytometry. A total of 87 healthy controls and 210 patients were enrolled, and the percentages of circulating T cells, CD4+ T cells, CD8+ T cells, double negative T cells (DNTs), CD4+ regulatory T cells (Tregs), CD8+ Tregs, B cells and regulatory B cells (Bregs) were measured. Among patients, B cells, Bregs and CD8+ Tregs increased significantly, while CD4+ Tregs dropped and soon reversed after ischemic stroke. CD4+ Tregs, CD8+ Tregs, and DNTs also showed high correlations with the infarct volume and neurological scores of patients. Moreover, these lymphocytes enhanced the predictive ability of long-term prognosis of neurological scores when added to basic clinical information. The percentage of CD4+ Tregs within lymphocytes showed high correlations with both acute and long-term neurological outcomes, which exhibited a great independent predictive ability. These findings suggest that CD4+ Tregs can be a biomarker to predict stroke outcomes and improve existing therapeutic strategies of immunoregulatory lymphocytes.

Plasma Exosomal MiRNAs Expression Profile in Mesial Temporal Lobe Epilepsy With Hippocampal Sclerosis: Case-Control Study and Analysis of Potential Functions.

BACKGROUND: To explore an expression profile in plasma exosomal miRNAs of mesial temporal lobe epilepsy with hippocampal sclerosis (mTLE + HS) patients and investigate the associated clinical significance and putative pathways involved. METHODS: Plasma exosomal miRNAs were measured in six mTLE + HS patients who were confirmed with pre-surgical stereo-electroencephalography and six without hippocampal sclerosis (mTLE-HS) using Illumina HiSeq 2500. Then six dysregulated miRNAs were chosen for validation in an independent sample of 18 mTLE + HS patients and 18 mTLE-HS controls using RT-qPCR. Receiver operating characteristic curve was conducted to evaluate the diagnostic value of miRNAs in HS. Bioinformatic analyses were conducted to reveal in which pathways these miRNAs were involved. RESULTS: We revealed that a total of 42 exosomal miRNAs were differentially expressed in mTLE + HS. Among them, 25 were increased and 17 decreased. After validation, hsa-miR-129-5p, -214-3p, -219a-5p, and -34c-5p were confirmed as being upregulated, while hsa-miR-421 and -184 were significantly downregulated in mTLE + HS. Moreover, hsa-miR-184 had the best diagnostic value for discriminating mTLE + HS with 88.9% sensitivity and 83.3% specificity. These six miRNAs regulated several genes from neurotrophin-, hippo-, p53-, TGF- beta-, HIF- 1-, mTOR-related pathways. CONCLUSION: Six miRNAs were dysregulated in mTLE + HS patients and targeted several genes. This result might facilitate pathological mechanistic studies of miRNAs in HS and represent potential diagnostic biomarkers. These provided the rationale for further confirmation studies in larger cohorts of prospective patients.

Impact of Covid-19 on the Behavior of Community Residents With Suspected Transient Ischemic Attack.

Background and Purpose: To investigate the impact of the novel coronavirus disease 2019 (Covid-19) on the behavior of those seeking medical attention for community residents suspected of having had a transient ischemic attack (TIA) during the pandemic. Methods: This was a community-based cross-sectional study with residents living in two communities located in the suburb of Shanghai. A face-to-face interview was prospectively conducted from 20 May 2020 to 30 June 2020 between community physicians and the community residents. Suspected TIA that occurred during the pandemic was identified by symptoms recalled from the community residents. The behavior of seeking medical attention after the suspected TIA was investigated. Results: A total of 873 community residents (517 from the Wujing community and 356 from the Maqiao community) took part in face-to-face interviews. Among them, 143 (16.38%) suspected TIA cases were identified. Less than 20% of the community residents suspected of having a TIA went to the hospital during the Covid-19 pandemic. The most common reason for not seeking medical care during the pandemic was still that symptoms disappeared quickly (94.9%); however, the pandemic did have an impact on behavior. Fear of in-hospital infection (55.1%) and of complicated procedures involved in seeking medical attention during the pandemic (55.9%) made community residents hesitate to seek medical attention after the suspected TIA. Residents with a dual attack within 1 week or with aphasia or dysarthria were more likely to seek medical attention during the pandemic. Conclusion: Our study indicated that the Covid-19 pandemic negatively affected the behavior of those seeking medical attention among community residents with suspected TIA and this might explain part of the reduction in patients presenting with stroke or TIA observed from other reports.

How Strong the Predictive Ability of the Variable Age and Stroke Severity for Patients Presented Late.

BACKGROUND AND PURPOSE: Age and stroke severity as 2 independent predictors have been included in many well-known prediction models. However, whether the model consisting of the 2 variables derived from early arrival group could bring equal clinical benefit for those patients presented late was unclear. This study aimed to investigate the performance of this transformation. METHODS: We enrolled ischemic stroke patients admitted to our stroke center within 3 days after symptom onset from January 1, 2018 to March 31, 2019.These patients were divided into 2 groups, early arrival group within 6 hours after onset and late arrival group between 6 hours and 3 days. Two multivariate logistic regression models were developed consisting of the variable age and stroke severity. The primary outcome was the unfavorable outcome which defined as modified Rankin Scale score of 3-6. The differences of the performance of the models were compared through 3 aspects (discrimination, calibration, and clinical utility). RESULTS: Five-hundred seventeen ischemic stroke patients were included in our study. There were 258 patients reached in our stroke center within 6 hours while 259 patients were not. The area under the curve were .78 (95% confidence interval .70-.87) for the model developed in the early arrival group and .82 (95% confidence interval .73-.90) for the model developed in the late arrival group respectively. The models calibrated well in the late arrival group. As for clinical utility, the net benefit of the model developed in the early group was only slightly lower than the model developed in the late arrival group. CONCLUSIONS: The prediction model consisting of the variable age and stroke severity derived from the early arrival group patients had the potential to be applied directly in the patients presented late.

Effect of particle size on adsorption of norfloxacin and tetracycline onto suspended particulate matter in lake.

Aquatic systems are important sinks of antibiotics; however, their final destination has not been completely elucidated. Therefore, we investigated the adsorption behaviors of suspended particulate matter (SPM) in lakes to support the analysis of the migration and transformation of antibiotics in lacustrine environments. SPM was collected from Meiliang Bay (ML) and Gonghu Bay (GH) in Lake Taihu, China, which was sieved into four particle sizes of >300, 150-300, 63-150, and <63 µm for subsequent antibiotic adsorption experiments. All particles exhibited rapid and substantial adsorption of tetracycline and norfloxacin. Most size fractions fit a Langmuir model, indicative of monomolecular adsorption, except the <63-µm fraction, which fit a Freundlich model. Particle size had a substantial influence on antibiotic adsorption; the 63-150-µm fraction had the greatest adsorption capacity, while the >300-µm fraction had the lowest capacity. The influence of particle size on adsorption was mainly related to SPM physicochemical properties, such as cation exchange capacity, surface area, and organic matter content, rather than types of functional groups. Considering the mass ratios, the <63-µm fraction had the greatest contribution to adsorption. Antibiotics adsorbed onto the SPM from ML and GH exhibited different behaviors. The ML SPM settled more readily into sediment, and larger, denser particles were more resistant to resuspension. Conversely, the GH SPM was more likely to be found in the water column, and larger, less-dense particles remained in the water column. These results help improve our understanding of the interactions between SPM and antibiotics in aquatic systems.

Regulatory T cells demonstrate significantly increased functions following stimulation with IL-2 in a Tim-3-dependent manner in intracranial aneurysms.

The formation of intracranial aneurysm (IA) is associated with the destruction of various cellular and structural components, which induces pathogenic inflammatory responses that further propagate tissue damage. The regulatory immune system can suppress exacerbated inflammation and offer tissue protection; however, previous studies by others and us have demonstrated that the regulatory T (Treg) cells were functionally impaired in IA patients. Hence, strategies that can improve Treg function in IA patients should be investigated. Based on our previous finding that IL-2 strongly elevated the expression of the checkpoint molecule Tim-3 in Treg cells, we examined the effect of IL-2 in the function of Treg cells from IA patients. External IL-2 significantly improved the proliferation of Treg cells, increased the expression of CTLA-4 and LAG-3, and enhanced Treg-mediated suppression of conventional T cell (Tconv) proliferation. Importantly, compared to the Tim-3- Treg cells, the Tim-3+ Treg cells presented comparable proliferation capacity, but significantly greater expressions of CTLA-4 and LAG-3 and significantly higher capacity to suppress Tconv proliferation. In addition, blocking Tim-3 abrogated IL-2-mediated enhancement of Tim-3+ Treg cells. We then investigated the IL-2 level in IA patients, and found that although IA patients and healthy controls presented similar serum IL-2 concentration, the concentrations of IL-1ß and TNF-α were significantly higher in IA patients than in healthy controls, signaling a relative reduction in IL-2 abundance. Together, we found that IL-2 could significantly enhance the function of Treg cells from IA patients in a Tim-3-dependent manner.

Patients with intracranial aneurysms presented defects in regulatory T cells, which were associated with impairment in Tim-3 upregulation.

Pathogenic inflammation contributes to aneurysm formation by mediating the destruction of the endothelium and the extracellular matrix and promoting pathogenic proliferation of smooth muscle cells. In mouse models, tolerance-inducing T regulatory (Treg) cells could significantly reduce the incidence and severity of aneurysms. Hence, it should be investigated why in human intracranial aneurysm (IA) patients, Treg cells failed to provide protection against aneurysm formation. In this study, the frequency and function of Treg cells in IA patients were examined. The frequency of Foxp3+ Treg cells was significantly lower in IA patients than in healthy controls. This downregulation was only specific to the Treg subset of CD4+ T cells, as the frequency of total CD4+ T cell was increased in IA patients. Subsequently, we found that the expressions of Treg-associated molecules, including Foxp3, CTLA-4, TGF-ß, and IL-10, were significantly lower in Foxp3+ Treg cells from IA patients than in Foxp3+ Treg cells from healthy controls. In both healthy controls and IA patients, Foxp3+ Treg cells were distinguished into a more potent Tim-3+ subset and a less potent Tim-3- subset. The Tim-3+ subset of Foxp3+ Treg cells was significantly reduced in IA patients. Signaling via IL-2, IL-7, IL-15 and IL-21 was shown to promote Tim-3 upregulation in CD4+ and CD8+ T cells. Interestingly, we found that Tim-3 could be upregulated in Treg cells via the same mechanism, but compared to the Treg cells from healthy controls, the Treg cells from IA patients presented defects in Tim-3 upregulation upon cytokine stimulation. Together, our results demonstrated that Foxp3+ Treg cells in IA patients presented reduced function, which was associated with a defect in Tim-3 upregulation.

Soluble galectin 9 potently enhanced regulatory T-cell formation, a pathway impaired in patients with intracranial aneurysm.

Patients with intracranial aneurysm (IA) present a dysregulated immune system with lower frequency of regulatory T (Treg) cells. Here, we examined whether galectin 9 (Gal-9), the natural ligand of Tim-3, could promote Treg cells in IA patients. We first discovered that the intracellular and extracellular Gal-9 was primarily expressed by CD4+ CD25- T conventional (Tconv) cells, and also by monocytes at lower levels, but rarely by CD4+ CD25+ Treg cells. In IA patients, the Gal-9 expression was significantly lower than in healthy controls. CD4+ CD25- Tconv cells could be induced into Foxp3-expressing induced Treg (iTreg) cells using a TGF-ß-containing milieu. We found that soluble Gal-9 significantly enhanced this process by potently upregulating the expression of Foxp3, IL-10 and TGF-ß in a concentration-dependent manner. In addition, in the absence of additional Gal-9, the level of Foxp3 upregulation was directly correlated with the level of intrinsic Gal-9 expression. Notably, the strength of external Gal-9-mediated effects was significantly lower in IA patients than in healthy controls. Using a Tim-3 blocking antibody, we found that the promotion of iTreg development by soluble Gal-9 was dependent on the Tim-3 signalling pathway. Overall, our investigations demonstrated that Gal-9 presented a critical role in the development of iTreg cells. However, this mechanism was impaired in IA patients due to lower expression of both Gal-9 and Tim-3.

Plant molecular responses to the elevated ambient temperatures expected under global climate change.

Environmental temperatures affect plant distribution, growth, and development. The Intergovernmental Panel on Climate Change (IPCC) predicts that global temperatures will rise by at least 1.5°C by the end of this century. Global temperature changes have already had a discernable impact on agriculture, phenology, and ecosystems. At the molecular level, extensive literature exists on the mechanism controlling plant responses to high temperature stress. However, few studies have focused on the molecular mechanisms behind plant responses to mild increases in ambient temperature. Previous research has found that moderately higher ambient temperatures can induce hypocotyl elongation and early flowering. Recent evidence demonstrates roles for the phytohormones auxin and ethylene in adaptive growth of plant roots to slightly higher ambient temperatures.

Effects of neuroserpin on clinical outcomes and inflammatory markers in Chinese patients with acute ischemic stroke.

OBJECTIVE: Neuroserpin (NSP) is known for its neuroprotective effects. The aim of this study was to investigate the relationship between NSP level and clinical outcomes and inflammatory markers in Chinese patients with acute ischemic stroke. METHODS: A total of 133 patients with acute cerebral infarction (ischemia group) and 44 controls were recruited. The modified Rankin Scale (mRS) was used to determine the functional outcome three months after onset. We investigated the relationship between serum NSP levels [on admission and a decrease in NSP levels (10 days after admission versus on admission)] and serum levels of several inflammatory markers. RESULTS: We confirmed that NSP levels on admission in the ischemia group were significantly higher than those in the control group. NSP levels in patients with good outcomes were significantly higher than those in patients with poor outcomes. NSP levels on admission were associated with having a good outcome in these patients. We found that a larger decrease in NSP levels (on admission vs. 10 days after admission) was correlated with lower serum levels of IL-6, IL-1ß, and ICAM-1 10 days after admission. CONCLUSIONS: A larger decrease in NSP levels related to lower levels of inflammatory marker, while higher NSP levels were associated with lower inflammatory markers and better functional outcomes. Decreasing the infarct size may play a role in this process. These results provide more evidence of the neuroprotective effect of NSP in cerebral ischemic patients. Decrease in the Serum NSP level and NSP level at admission may be considered as potential predictive factors for outcome of acute ischemic stroke.

Neuroserpin Protects Rat Neurons and Microglia-Mediated Inflammatory Response Against Oxygen-Glucose Deprivation- and Reoxygenation Treatments in an In Vitro Study.

BACKGROUND/AIMS: Neuroserpin (NSP) is known for its neuroprotective role in cerebral ischemic animal models and patients. Our laboratory conducted a series of investigations on the neuroprotection of NSP in different cells in the brain. In the present study, we further observe the effects of NSP on neurons and microglia-mediated inflammatory response following oxygen-glucose deprivation (OGD), and explore possible mechanisms related to neuroprotection of OGD in the central nervous system (CNS). METHODS: Neurons and microglia from neonatal rats were treated with OGD followed by reoxygenation (OGD/R). To confirm the effects of NSP, the neuronal survival, neuronal apoptosis, and lactate dehydrogenase (LDH) release were measured in cultured neurons. Furthermore, the levels of IL-1ß and nitric oxide (NO) release were also detected in cultured microglia. The possible mechanisms for the neuroprotective effect of NSP were explored using Western blot analysis. RESULTS: NSP administration can reverse abnormal variations in neurons and microglia-mediated inflammatory response induced by OGD/R processes. The neuronal survival rate, neuronal apoptosis rate, and LDH release were significantly improved by NSP administration in neurons. Simultaneously, the release of IL-1ß and NO were significantly reduced by NSP in microglia. Western blot showed that the expression of ERK, P38, and JNK was upregulated in microglia by the OGD/R treatment, and these effects were significantly inhibited by NSP. CONCLUSION: These data verified the neuroprotective effects of NSP on neurons and microglia-mediated inflammatory response. Inhibition of the mitogen-activated protein kinase (MAPK) signaling pathways might play a potential role in NSP neuroprotection on microglia-mediated inflammatory response, which needs further verification.

Effects of intracerebral hemorrhage on 5-hydroxymethylcytosine modification in mouse brains.

The past decade has resulted in an increase in the knowledge of molecular mechanisms underlying brain injury induced by intracerebral hemorrhage (ICH). Recent advances have provided a link between epigenetic modification and the regulation of gene expression. 5-hydroxymethylcytosine (5hmC) converted from 5-methylcytosine by the ten-eleven translocation (TET) family of proteins has emerged as a new epigenetic modification. While the dynamics of 5hmC during cerebral ischemia have recently been reported, whether 5hmC is involved in ICH remains unexplored. In this study, we investigated the effects of ICH on DNA hydroxymethylation. We showed that the global level of 5hmC rapidly decreased as early as 24 hours after ICH and persisted until 72 hours. Furthermore, the level of 5hmC in the CpG-rich regions of Akt2, Pdpk1 and Vegf genes was significantly decreased with a minimum level observed at 48 hours or 72 hours. Decreased 5hmC was observed in parallel with an increase in 5-methylcytosine over this time course, and mRNA levels of Akt2, Pdpk1 and Vegf were downregulated upon ICH injury. Finally, Tet1, Tet2 and Tet3 mRNA levels were dramatically decreased in the ICH brain. Our study for the first time established the correlation between DNA hydroxymethylation and ICH injury. Further investigations should examine whether 5hmC modification could be a therapeutic target for the treatment of ICH injury.