Clinical characteristics of autoimmune encephalitis with co-existence of multiple anti-neuronal antibodies.

BACKGROUND: An increasing number of cases of autoimmune encephalitis (AE) with co-existing multiple anti-neuronal antibodies have been reported in recent years. However, the clinical significance of the concurrent presence of multiple anti-neuronal antibodies in patients with AE remains unclear. METHODS: We retrospectively enrolled AE patients with multiple anti-neuronal antibodies treated at our center between August 2019 and February 2022. We also reviewed cases reported in multiple literature databases. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed on selection process. And then the clinical and laboratory data of these cases were collected for review and summary. RESULTS: A total of 83 AE cases with multiple antibodies (9 cases from our center and 74 cases from the literatures reviewed) were identified. In our center, nine patients presented with encephalitis symptoms, clinically characterized as disturbed consciousness, seizures, cognitive impairment, and psychiatric disorders. Of the 83 cases, 73 cases had co-existence of 2 types of antibodies, 8 cases had 3 types, and 2 cases had 4 types. Thirty-nine cases (39/83, 46.9%) were confirmed or suspected of also having a tumor, of which the most common was lung cancer (28/83, 33.7%). Partial or complete recovery was achieved in 57 cases (57/83, 68.6%), while 26 cases (26/83, 31.3%) died during treatment or follow-up. CONCLUSIONS: AE with co-existing multiple anti-neuronal antibodies is a specific subgroup, that is increasingly recognized in clinical practice. The co-existence of multiple anti-neuronal antibodies has a major impact on clinical features, disease progression, and prognosis.

Comparison between MRI-negative and positive results and the predictors for a poor prognosis in patients with idiopathic acute transverse myelitis.

BACKGROUND: Idiopathic acute transverse myelitis (IATM) is a focal inflammatory disorder of the spinal cord that results in motor, sensory, and autonomic dysfunction. However, the comparative analysis of MRI-negative and MRI-positive in IATM patients were rarely reported. OBJECTIVES: The purpose of this study was to compare MRI-negative with MRI-positive groups in IATM patients, analyze the predictors for a poor prognosis, thus explore the relationship between MRI-negative and prognosis. METHODS: We selected 132 patients with first-attack IATM at the First Affiliated Hospital of Nanchang University from May 2018 to May 2022. Patients were divided into MRI-positive and MRI-negative group according to whether there were responsible spinal MRI lesions, and good prognosis and poor prognosis based on whether the EDSS score ≥ 4 at follow-up. The predictive factors of poor prognosis in IATM patients was analyzed by logistic regression models. RESULTS: Of the 132 patients, 107 first-attack patients who fulfilled the criteria for IATM were included in the study. We showed that 43 (40%) patients had a negative spinal cord MRI, while 27 (25%) patients were identified as having a poor prognosis (EDSS score at follow-up ≥ 4). Compared with MRI-negative patients, the MRI-positive group was more likely to have back/neck pain, spinal cord shock and poor prognosis, and the EDSS score at follow-up was higher. We also identified three risk factors for a poor outcome: absence of second-line therapies, high EDSS score at nadir and a positive MRI result. CONCLUSIONS: Compared with MRI-negative group, MRI-positive patients were more likely to have back/neck pain, spinal cord shock and poor prognosis, with a higher EDSS score at follow-up. The absence of second-line therapies, high EDSS score at nadir, and a positive MRI were risk factors for poor outcomes in patients with first-attack IATM. MRI-negative patients may have better prognosis, an active second-line immunotherapy for IATM patients may improve clinical outcome.

Plasma level of miR-99b may serve as potential diagnostic and short-term prognostic markers in patients with acute cerebral infarction.

OBJECTIVE: The aim of the present study is to explore the potential diagnostic and prognostic value of plasma levels of miR-99 family for patients with acute cerebral infarction (ACI). METHODS: A total of 112 patients who have been diagnosed with ACI were enrolled in this study, and 112 healthy volunteers were served as the controls. The plasma of the patients and controls were collected, and total RNAs were isolated, and the expression levels of miR-99a, miR-99b, and miR-100 in the plasma of patients and controls were compared determined by RT-qPCR methods; moreover, the receiver operating characteristic (ROC) curve has been drawn to determine whether the plasma levels of miR-99b can distinguish patients with ACI from the controls; furthermore, the short-term prognosis of the patients was evaluated by glasgow outcome scale (GOS), and the correlation between the plasma levels of miR-99b and the GOS of the patients was evaluated. Finally, the correlation between the plasma level of miR-99 and VEGF of ACI patients was analyzed. RESULTS: It was observed that miR-99b was significantly decreased in the plasma of ACI patients compared with the healthy controls (P < .01), while the plasma levels of miR-99a and miR-100 showed no significant differences between the patients with ACI and the healthy controls; moreover, the area under the curve (AUC) of miR-99b for the diagnosis of ACI was 0.8882 (95% confidence interval (CI), 0.8451-0.9313), suggesting that plasma level of miR-99b is a sensitive marker to distinguish patients with ACI from the healthy volunteers; furthermore, the serum level of miR-99b was negatively correlated with GOS score of the patients (r = -.56, P < .001); finally, the plasma level of miR-99b was negatively correlated with the levels of VEGF (r = -.3013, P = .0012). CONCLUSION: miR-99b was down-regulated in plasma of patients with ACI, and plasma level of miR-99b may be a potential diagnostic and prognostic marker for the diagnosis and treatment of ACI.

Changes of B cell subsets in central pathological process of autoimmune encephalomyelitis in mice.

BACKGROUND: Multiple sclerosis is a demyelinating and autoimmune disease and its immune response is not fully elucidated. This study was conducted to examine the pathological changes and B cell subsets in experimental autoimmune encephalomyelitis (EAE) mice, and analyze the expression of triosephosphate isomerase (TPI) and GADPH to define the role of B cell subsets in the disease. RESULTS: Female C57BL/6 mice were randomly divided into EAE group (n = 18) and control (n = 18). During the experiments, the weight and nerve function scores were determined. The proportions of B cell subsets in the peripheral blood were measured by flow cytometry. Seven, 18 and 30 days after immunization, the brain and spinal cord tissues were examined for the infiltration of inflammatory cells using hematoxylin-eosin (HE) HE staining and the demyelination using Luxol fast blue staining. The expression of B cell-related proteins was detected immunohistochemistrially and the expression of antigenic TPI and GADPH was analyzed using enzyme-linked immunosorbent assay (ELISA). HE staining showed that mice had more severe EAE 18 d than 7 d after modelling, while the symptoms were significantly relieved at 30 d. The results were consistent with the weight measurements and neural function scores. Immunohistochemistry studies showed that B cells aggregated in the spinal cord, but not much in the brain. Flow cytometry studies showed that there were more B cells in control than in EAE models from day 7 and the difference was narrowed at day 30. The level of plasma cells increased continuously, reached the top at day 21 and obviously declined at day 30. On other hand, the numbers of memory B cells increased gradually over the experimental period. The numbers of plasma and memory B cells were similar between the control and EAE mice. ELISA data revealed that the brain contents of TPI and GAPDH were higher in EAE mice than in control at day 7, while at day 18, the levels were reversed. CONCLUSIONS: In the central pathological process of EAE mice, B cells exert role through the mechanism other than producing antibodies and the levels of brain TPI and GADPH are related to the severity of autoimmune induced-damage.

Antibiotic bedaquiline effectively targets growth, survival and tumor angiogenesis of lung cancer through suppressing energy metabolism.

Tumor angiogenesis plays essential roles during lung cancer progression and metastasis. Therapeutic agent that targets both tumor cell and vascular endothelial cell may achieve additional anti-tumor efficacy. We demonstrate that bedaquiline, a FDA-approved antibiotic drug, effectively targets lung cancer cells and angiogenesis. Bedaquiline dose-dependently inhibits proliferation and induces apoptosis of a panel of lung cancer cell lines regardless of subtypes and molecular heterogeneity. Bedaquiline also inhibits capillary network formation of human lung tumor associated-endothelial cell (HLT-EC) on Matrigel and its multiple functions, such as spreading, proliferation and apoptosis, even in the presence of vascular endothelial growth factor (VEGF). We further demonstrate that bedaquiline acts on lung cancer cells and HLT-EC via inhibiting mitochondrial respiration and glycolysis, leading to ATP reduction and oxidative stress. Consistently, oxidative damage on DNA, protein and lipid were detected in cells exposed to bedaquiline. Importantly, the results obtained in in vitro cell culture are reproducible in in vivo xenograft lung cancer mouse model, confirming that bedaquiline suppresses lug tumor growth and angiogenesis, and increases oxidative stress. Our findings demonstrating that energy depletion is effectively against lung tumor cells and angiogenesis. Our work also provide pre-clinical evidence to repurpose antibiotic bedaquiline for lung cancer treatment.

Increased expression of formin-like 3 contributes to metastasis and poor prognosis in colorectal carcinoma.

Formin-like 3 (FMNL3), a member of diaphanous-related formins subfamily, plays an important role in cytoskeleton reorganization, cell adhesion and cancer cell invasion in vitro. This study aimed to explore the expression of FMNL3 in colorectal carcinoma (CRC) cell-lines and tissues, and further evaluate its prognostic value and correlation with the clinicopathological parameters, and also investigate the effects of FMNL3 gene silencing on the growth and metastasis of CRC in vivo. Immunohistochemical analysis showed that FMNL3 protein was distributed in a punctuate aggregation pattern and located mainly in the cytoplasm of glandular cavity side, close to the nucleus of CRC cells. The positive rate of FMNL3 expression was 87.5% (84/96) in CRC, which was significantly higher than that in adjacent normal mucosa (30%, 9/30). Moreover, FMNL3 protein expressed far more in primary CRC with metastasis and corresponding lymph nodes metastatic CRC than in primary CRC without metastasis. Increased expression of FMNL3 was closely correlated with tumor size, differentiation, serosal invasion, and both lymph node metastasis and distant metastasis. However, it was not correlated with patients' age and gender. According to Kaplan-Meier survival analyses, patients with FMNL3 high expression level had lower overall survival rate than that with FMNL3 low expression level. Univariate and multivariate analyses revealed that high FMNL3 expression was a significant and independent prognostic predictor of patients with CRC. In addition, FMNL3 mRNA and protein levels were substantially up-regulated in CRC-metastasis-derived cell lines, as compared to those in primary-CRC-derived ones. FMNL3 gene silencing suppressed the growth and metastasis of CRC in vivo. In conclusion, FMNL3 plays an important role in the progression and metastasis of CRC and may be a novel potential prognostic predictor and therapeutic target for patients with CRC.

Inhibition of xanthine oxidase activity by gnaphalium affine extract.

OBJECTIVE: To evaluate the inhibitory effect of Gnaphalium affine extracts on xanthine oxidase (XO) activity in vitro and to analyze the mechanism of this effect. METHODS: In this in vitro study, Kinetic measurements were performed in 4 different inhibitor concentrations and 5 different xanthine concentrations (60, 100, 200, 300, 400 Μmol/L). Dixon and Lineweaver-Burk plot analysis were used to determine Ki values and the inhibition mode for the compounds isolated from Gnaphalium affine extract. RESULTS: Four potent xanthine oxidase inhibitors were found in 95% ethanolic (v/v) Gnaphalium affine extract. Among them, the flavone Eupatilin exhibited the strongest inhibitory effect on XO with a inhibition constant (Ki) of 0.37 Μmol/L, lower than the Ki of allopurinol (4.56 mol/L), a known synthetic XO inhibitor. Apigenin (Ki of 0.56 Μmol/L, a proportion of 0.0053‰ in Gnaphalium affine), luteolin (Ki of 2.63 Μmol/L, 0.0032‰ in Gnaphalium affine) and 5-hydroxy-6,7,3',4'-tetramethoxyflavone (Ki of 3.15 Μmol/L, 0.0043‰ in Gnaphalium affine) also contributed to the inhibitory effect of Gnaphalium affine extract on XO activity. CONCLUSIONS: These results suggest that the use of Gnaphalium affine in the treatment of gout could be attributed to its inhibitory effect on XO. This study provides a rational basis for the traditional use of Gnaphalium affine against gout.

Rituximab-induced gut microbiota changes in Chinese neuromyelitis optica spectrum disorders.

BACKGROUND: Recent evidence shows that immunosuppressive agents can affect the gut microbiota in autoimmune diseases. However, the relationship between the gut microbiome and B-cell depletion immunotherapy in neuromyelitis optica spectrum disorder (NMOSD) remains poorly understood. OBJECTIVES: To evaluate the distinct intestinal microbial patterns and serum cytokine levels after short-term rituximab treatment (three months) in patients with NMOSD. METHODS: Firstly, we conducted a cross-sectional study involving 46 treatment-naïve NMOSD patients and 48 matched healthy controls. We collected fecal specimens, which were then analyzed using next-generation sequencing, and quantified serum cytokines. Subsequently, fecal and serum samples were re-collected and re-evaluated in 31 of the 46 treatment-naïve NMOSD patients after RTX treatment. RESULTS: Comparing the gut microbiome of treatment-naïve NMOSD patients to that of healthy controls revealed low α-diversity and distinct microbial compositions in the former. The microbial composition in NMOSD patients underwent changes following three months of RTX treatment. Specifically, the levels of IL-17F and IL-6 decreased, while those of IL-10 and TNFα increased after RTX treatment. LEfSe analysis identified 27 KEGG categories with significantly differential abundances between NMOSD patients and RTX treatment group. CONCLUSIONS: Our study provides a comprehensive understanding of the gut microbiota landscape in the context of B-cell depletion immunotherapy. We observed dysbiosis in the gut microbiome of NMOSD patients, which was partially alleviated by three months of RTX treatment. This suggests that B-cell depletion may play a crucial role in driving changes in the gastrointestinal environment.

Treatment algorithms of relapsing multiple sclerosis: an exploration based on the available disease-modifying therapies in China.

Multiple sclerosis (MS) was defined as a rare disease in China due to its low prevalence. For a long time, interferon ß was the only approved disease-modifying therapy (DMT). Since the first oral DMT was approved in 2018, DMT approval accelerated, and seven DMTs were approved within 5 years. With an increasing number of DMTs being prescribed in clinical practice, it is necessary to discuss the standardized MS treatment algorithms depending on the disease activity and DMT availability. In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country.

Treatment algorithms of relapsing multiple sclerosis in China In this review paper, more than 20 Chinese experts in MS have reviewed the therapeutic progress of MS in China and worldwide and discussed algorithms for treating relapsing MS (RMS) based on the available DMTs in China, providing insights for establishing the standardized RMS treatment algorithms in this country: 1) CIS and RRMS account for more than 90% of the MS patients and most of them are mild to moderate; 2) MS patients should initiate DMT treatments as soon as the disease has been diagnosed in order to reduce the risk of disease progression; 3) Patients who have been diagnosed with MS should start treatment with fundamental DMTs unless the disease course has been highly active; 4) MAGNIMS score may be a suitable and simplified assessment tool for measuring treatment response to DMTs; 5) Patients treated with corticosteroids and NSIS should be switched to the standardized DMT treatment during remission in accordance with disease activity.

Extensive loss of connexins in Baló's disease: evidence for an auto-antibody-independent astrocytopathy via impaired astrocyte-oligodendrocyte/myelin interaction.

Extensive aquaporin-4 (AQP4) loss without perivascular deposition of either activated complement or immunoglobulins is a characteristic of Baló's disease. Our aim in this study was to investigate the relationship between astrocytopathy and demyelination in Baló's disease, focusing on connexins (Cx), which form gap junctions among glial cells and myelin. Autopsied specimens from four cases that provided seven actively demyelinating concentric lesions infiltrated with numerous CD68(+) macrophages were immunohistochemically examined for the astrocyte markers glial fibrillary acidic protein (GFAP), AQP4, Cx43, Cx30 and megalencephalic leukoencephalopathy with subcortical cyst 1 (MLC1). Specimens were also stained for oligodendrocyte/myelin markers, namely Cx32, Cx47, myelin-associated glycoprotein (MAG), myelin oligodendrocyte glycoprotein (MOG), oligodendrocyte-specific protein (OSP) and Nogo-A. Serum samples from six patients that had undergone magnetic resonance imaging, confirming a diagnosis of Baló's disease, were assayed for the presence of anti-Cx43, -Cx32 and -AQP4 antibodies. Despite the presence of numerous GFAP- and MLC1-positive astrocytes, there was a marked decrease in the levels of Cx43, Cx32 and Cx47. At the leading edges, Cx43 and AQP4 were mostly absent despite positive GFAP, MLC1, Cx32, Cx47, MOG, MAG, and OSP immunoreactivity. Of the six Baló's disease patients, none were positive for anti-Cxs or -AQP4 antibodies. Baló's disease is characterized by extensive loss of Cxs and AQP4, and a lack of auto-antibodies to Cxs and AQP4. Loss of Cx43 and AQP4 in the presence of other oligodendrocyte/myelin proteins at the leading edges suggests the possibility that auto-antibody-independent astrocytopathy may contribute to disease pathology via the disruption of astrocyte-oligodendrocyte/myelin interactions.

Correlation of transrenal DNA with non-small-cell lung cancer in noninvasive disease monitoring.

Background: The study aims to use noninvasive transrenal DNA in advanced non-small-cell lung cancer (NSCLC) patients for treatment monitoring and prognosis. Methods: Urine specimens were collected longitudinally for 103 late-stage NSCLC patients. Detection of targetable mutations in transrenal DNA was achieved by digital droplet PCR. Patients' overall survival outcomes were correlated with levels of transrenal DNA. Results: Corresponding patients' matched tumor results demonstrated concordance rate of 95.6% with transrenal DNA. A significant decline in levels was observed after treatment initiation. We observed changes in transrenal DNA levels to be significantly associated with survival for patients (p < 0.0001). Conclusion: Our results demonstrated strong predictive values of transrenal DNA to better identify patients with poorer survival outcomes and may further complement disease management.

Association of susceptibility to multiple sclerosis in Southern Han Chinese with HLA-DRB1, -DPB1 alleles and DRB1-DPB1 haplotypes: distinct from other populations.

Association of HLA class II with multiple sclerosis (MS) has been widely studied in both Western and Oriental populations. However, such an association is not well documented in Chinese. The objective of this study was to examine the association between the susceptibility to conventional MS in Southern Chinese with HLA-DRB1,-DPB1 alleles and putative DRB1-DPB1 haplotypes. Genotyping of HLA-DRB1 and -DPB1 alleles was performed in 60 patients with conventional MS and 95 controls. Allele frequencies were compared between patients and controls to identify MS-associated alleles. Relative predisposing effect method was used to compare haplotype frequencies in patients and controls and to identify possible predisposing DRB1-DPB1 haplotypes, which were further examined for differences in haplotype carriage rates between the two groups. We found that the allele frequency of DRB1*1501 was not different between patients (18.3%) and controls (21.1%) (p = 0.837). In contrast, frequency of the DPB1*0501 allele was significantly higher in patients (90%) than in controls (67.4%) (odds ratio = 4.36, p = 0.0013, pcorr = 0.025). DRB1-DPB1 linkage haplotype in patients (8.33%) was significantly higher than in controls (0%) (p < 0.0001) and the carriage rate of this haplotype was significantly increased in patients (15%) as compared with controls (0%) (p = 0.00013, pcorr = 0.003). Combined, these results suggest that HLA-DRB1*1501 is not associated with susceptibility to conventional MS in Southern Chinese. Instead, both the DPB1*0501 allele and the DRB1*1602- DPB1*0501 haplotype are strong predisposing factors for conventional MS in this population. Our results establish that the HLA profiles of MS in Southern Chinese are distinct from other populations.

Serum YKL-40 level is associated with severity of interstitial lung disease and poor prognosis in dermatomyositis with anti-MDA5 antibody.

OBJECTIVE: We aimed to investigate the clinical value of checking serum chitinase-3-like-1 protein (YKL-40) levels in anti-MDA5 antibody-positive dermatomyositis (anti-MDA5+DM) patients. METHODS: One hundred and five consecutive anti-MDA5+DM patients and 44 healthy controls were enrolled in this study. Baseline and follow-up serum YKL-40 were detected by ELISA. We evaluated the association of YKL-40 with rapidly progressive interstitial lung disease (RPILD), severity of interstitial lung disease (ILD), and ILD-related survival. RESULTS: Forty-one out of 105 anti-MDA5+DM patients had RPILD at the time of serum sample collection (39.0%). Serum YKL-40 levels were significantly higher in anti-MDA5+DM patients with RPILD compared with those without (p = 0.011). One month after treatment, patients with aggravated ILD had increased YKL-40 levels, while those with stable/improved ILD had decreased YKL-40 levels. Higher serum levels of ferritin and YKL-40, as well as lower peripheral CD3+T cell counts, were independently associated with poorer prognosis. Kaplan-Meier survival curve showed that the 6 months survival rate in patients with high serum YKL-40 level (> 80 ng/ml) was significantly lower than that in patients with low YKL-40 level (≤ 80 ng/ml) (67% vs 89%, p < 0.01). CONCLUSION: YKL-40 can be useful as an indicator for the occurrence of RPILD and correlates with severity of ILD and poor prognosis in anti-MDA5+DM patients. Closely monitoring and intensive treatment are suggested in anti-MDA5+DM patients showing high level of YKL-40, especially levels > 80 ng/ml.

The Effect of Triggering Receptor Expressed by Myeloid Cells 2 Modified Bone Marrow Mesenchymal Stem Cells on Alzheimer's Disease-Mouse Model.

OBJECTIVE: This study aims to explore the effect of TREM2 modified BMSCs on hippocampus of AD mice. METHODS: Mouse bone marrow mesenchymal stem cells were isolated and identified. APP/PS1 double transgenic mice were confirmed to be AD model and divided into 4 groups: control group, MSCs group, MSCs+vector group and MSCs+pEGFP-TREM2 group. RESULTS: The incubation period and the number of errors in the MSCs+pEGFP-TREM2 group were significantly decreased than that of control group after 3 days. The quantity and area of Aß deposition in MSCs+pEGFP-TREM2 group were significantly smaller than that of control group. Aß40 and Aß42 levels were significantly decreased most in MSCs+pEGFP-TREM2 group. The expression levels of TREM2 and DAP12 significantly increased in the MSCs+pEGFP-TREM2 group. CONCLUSIONS: TREM2 modified bone marrow MSCs affected the ability of learning and memory of AD model mice and this mechanism may be related to the expression of TREM2 and DAP12 genes.

A Diagnostic Formula for Discrimination of Tuberculous and Bacterial Meningitis Using Clinical and Laboratory Features.

Background: The discrimination of tuberculous meningitis and bacterial meningitis remains difficult at present, even with the introduction of advanced diagnostic tools. This study aims to differentiate these two kinds of meningitis by using the rule of clinical and laboratory features. Methods: A prospective observational study was conducted to collect the clinical and laboratory parameters of patients with tuberculous meningitis or bacterial meningitis. Logistic regression was used to define the diagnostic formula for the discrimination of tuberculous meningitis and bacterial meningitis. A receiver operator characteristic curve was established to determine the best cutoff point for the diagnostic formula. Results: Five parameters (duration of illness, coughing for two or more weeks, meningeal signs, blood sodium, and percentage of neutrophils in cerebrospinal fluid) were predictive of tuberculous meningitis. The diagnostic formula developed from these parameters was 98% sensitive and 82% specific, while these were 95% sensitive and 91% specific when prospectively applied to another 70 patients. Conclusion: The diagnostic formula developed in the present study can help physicians to differentiate tuberculous meningitis from bacterial meningitis in high-tuberculosis-incidence-areas, particularly in settings with limited microbiological and radiological resources.

Atorvastatin ameliorates the contractile dysfunction of the aorta induced by organ culture.

Statins are widely used in the treatment of hypercholesterolemia. Studies have demonstrated that statins could maintain vascular contractile function through inhibiting the transformation of vascular smooth muscle cells (VSMCs) from the contractile phenotype to the synthetic phenotype. However, the underlying mechanisms have not been fully elucidated. The effect of atorvastatin on the thoracic aorta of Sprague-Dawley rats cultured in serum-free conditions in vitro was evaluated. Aortic constriction was induced by high potassium, phenylephrine, and CaCl2. The protein expression levels of α1 adrenoceptor; inositol 1,4,5-trisphosphate (IP3) receptor; protein kinase Cδ (PKCδ); stromal interaction molecule 1 (STIM1); high-voltage activated dihydropyridine-sensitive (L type, Cav1.2) channels; and two contractile phenotype marker proteins [α-smooth muscle actin (α-SMA) and myosin (SM-MHC)] were determined by western blotting. Compared with the fresh control, the constriction of rat aorta was impaired after culture in serum-free medium for 24 h. The impaired contraction of cultured aortas was mediated by Cav1.2 and store-operated Ca2+ (SOC) channel, which could be improved by atorvastatin at 20 µM. The protein expression levels of α1 adrenoceptor, IP3 receptor, PKCδ, STIM1, Cav1.2, α-SMA, and SM-MHC in the aortas cultured in serum-free conditions were decreased significantly. Atorvastatin partially prevented the reduction in the contractility and the downregulation of these proteins in cultured aortas. The transformation of the VSMC phenotype is associated with the vasoconstriction dysfunction of cultured aortas. Atorvastatin may protect vascular function by modulating calcium signaling pathways.

Photovoltage mechanism for room light conversion of citrate stabilized silver nanocrystal seeds to large nanoprisms.

We investigate the photoconversion of aqueous 8 nm Ag nanocrystal seeds into 70 nm single crystal plate nanoprisms. The process relies on the excitation of Ag surface plasmons. The process requires dioxygen, and the transformation rate is first-order in seed concentration. Although citrate is necessary for the conversion, and is consumed, the transformation rate is independent of citrate concentration. We propose a mechanism that accounts for these features by coupling the oxidative etching of the seed and the subsequent photoreduction of aqueous Ag(+). The reduced Ag deposits onto a Ag prism of specific size that has a cathodic photovoltage resulting from plasmon "hot hole" citrate photo-oxidation. This photovoltage mechanism also explains recent experimental results involving single and dual wavelength irradiation and the core/shell synthesis of Ag layers on Au seeds.

Functions of T-cell subsets and their related cytokines in the pathological processes of autoimmune encephalomyelitic mice.

OBJECTIVE: This study aims to observe the pathological changes of the brain and spinal cord in an experimental allergic encephalitis (EAE) mice model in the early onset, peak and remission periods of the disease, to detect the changes in the T-cell subsets and cytokine levels, to analyze the types of immune response and related principles in the different stages of the disease. METHODS: C57BL/6 mice were randomly divided into two groups: the EAE group (n = 18) and the control group (n = 18). C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein (MOG) 35-55 polypeptide/complete Freund's adjuvant (CFA) to establish the EAE mouse model. In the control group, the mice were treated with normal saline. The weights of the mice were recorded during the experiment. Peripheral blood was collected on the 0 day, 3rd day, 7th day, 14th day and 21st day after immunization, and the levels of T-cell subsets were detected by flow cytometry. The brain and spinal cord were taken on the 7th day (early onset), 18th day (peak) and 30th day (remission) after immunization. HE staining was used to observe the infiltration of inflammatory cells, and LFB staining was used to observe the loss of the myelin sheath. The immunohistochemical method was used to detect the T cells and B cell related proteins, and an ELISA assay was used to detect the changes of IL-4, IL-6, IL-10, IL-12, IL-17, IL-23, TNF-α, IFN-γ and TGF-ß in mouse brain tissue. The interactions between the T cell subsets and cytokines, the types of immune responses of the EAE mice in different stages of the disease, and their related principles were analyzed. RESULTS: The symptoms of the EAE mice after treatment for 18 d were more severe than those at 7 d in the mice, while the symptoms were significantly relieved at 30 d. These findings coincide with the results of the weight measurement in mice. The immunohistochemical detection of T-cell and B-cell subset related factors showed that T cells accumulated in the brains of the EAE mice. In contrast, there was no obvious aggregation of B cells. The Th17 and Th2 levels in the T cell subsets in the EAE group were higher than those in the control group from the beginning of the treatment to the twenty-first day after the treatment. The level of Th1 in the EAE group was higher than it was in the control group on the seventh day after the treatment, and it was lower during the rest of the time than it was in the control group. There was no significant difference in the level of γδT between the control group and the EAE group. ELISA results showed that the cytokines in the EAE group were higher than they were in the control group on the seventh day after treatment, but the levels of IFN-γ, IL-12, TGF-ß, and IL-23 in EAE group were lower than they were in the control group on the 18th day after the treatment. There was no significant difference in the levels of cytokines between the two groups on the 30th day after the treatment. CONCLUSIONS: At the different disease stages of the EAE mice, the balance between Th1 and Th2 and the balance of Th17 differentiation changed. Th17 promoted the development of the disease, and Th2 was more effective in restoring health.

Relationship of atopic dermatitis with stroke and myocardial infarction: A meta-analysis.

BACKGROUND: Lots of previous reports have suggested a potential association of atopic dermatitis (AD) with stroke and myocardial infarction (MI). However, the result is still controversial, Consequently, we conducted this meta-analysis to estimate the relationship of AD with Stroke and MI. METHODS: PubMed, Embase, and Web of Science databases were searched from inception to June 2018. Stroke and MI were considered as a composite endpoint. We calculated pooled hazard ratios (HRs) with 95% confidence intervals (CIs). Subgroup and sensitivity analysis were performed to assess the potential sources of heterogeneity of the pooled estimation. RESULTS: A total of 12 articles with 15 studies involving 3,701,199 participants were included in this meta-analysis. Of these, 14 studies on stroke and 12 on MI. Pooled analysis showed participants with AD experienced a significant increased risk of stroke (combined HR, 1.15; 95% CI, 1.08-1.22; P = .000) and MI (combined HR, 1.13; 95% CI, 1.02-1.24; P = .014), compared with participants without AD. The risk of stroke and MI was significant both in male subjects (stroke: HR: 1.33, 95% CI: 1.14-1.56; MI: HR: 2.01, 95% CI: 1.31-3.08), but not in female subjects (HR: 1.02, 95% CI: 0.77-1.35; MI: HR: 0.98, 95% CI: 0.72-1.32). The results were more pronounced for ischemic stroke (HR: 1.16, 95% CI: 1.13-1.19) in the stratified with stroke type. Stratifying by AD type, the risk of stroke was significant in severe AD (HR: 1.29, 95% CI: 1.08-1.54) and moderate AD (HR: 1.11, 95% CI: 1.01-1.22) for MI. CONCLUSIONS: AD is independently associated with an increased risk of stroke and MI, especially in male subjects and ischemic stroke and the risk is associated with the severity of AD.