Jionoside A1 alleviates ischemic stroke ischemia/reperfusion injury by promoting Nix-mediated mitophagy.

In ischemia-reperfusion injury in ischemic stroke, mitophagy, which can remove damaged mitochondria, reduce cytotoxic damage, and enhance neurological recovery, is crucial. Jionoside A1 is a substance found in the traditional Chinese herb Rehmannia glutinosa, which may have neuroprotective effects. The fundamental objective of this work was to find out Jionoside A1's contribution to ischemia/reperfusion injury in ischemic stroke. The oxygen-glucose deprivation/reperfusion (OGD-Rep) model and the right transient middle cerebral artery occlusion (tMCAO) model were established. Jionoside A1 was used for treatment. We utilized a tiny interfering RNA (siRNA) to lower Nix expression. The results suggest that Jionoside A1 may reduce ischemic stroke. By lowering the consequences of ischemia/reperfusion injury, Rehmannia glutinosa can be utilized to treat ischemic stroke. These discoveries provide fresh experimental information for the investigation of ischemic stroke ischemia/reperfusion injury and provide some theoretical justification for their application.

Brain changes correlate with neuropathic pain in patients with neuromyelitis optica spectrum disorders.

BACKGROUND: Neuropathic pain (NP) is a highly disturbing sensory experience in patients with neuromyelitis optica spectrum disorders (NMOSD). However, the brain changes in NMOSD patients with NP have rarely been studied. OBJECTIVE: The aim of the cross-sectional and follow-up longitudinal study was to investigate the brain changes in NMOSD patients with NP. METHODS: In the cross-sectional study, comparisons were performed between groups with NP (W-NP) and without NP (Wo-NP), and age, sex and years of education were adjusted. We compared the voxel-wise whole-brain gray matter (GM) volume, cortical thickness (CT), cortical surface area (CSA) and local gyrification index (LGI). Probabilistic tractography started from regions with significant between-group differences in GM volume, CT, CSA and LGI. We also compared fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) of the white matter (WM) skeleton using Tract-Based Spatial Statistics (TBSS). In the longitudinal study, the patients were followed for 2.0±0.0 years and underwent the same imaging scanning as the cross-sectional study. Changes of the CT, CSA, LGI and WM were obtained. RESULTS: Patients in the W-NP group were older than those in the Wo-NP group and showed significantly reduced LGI of the left temporal lobe and adjacent regions(regions of interest, ROIs), which participated in neuropathic pain processing, possibly by emotion and attention control. Probabilistic tractography started from ROIs, and the generated WM tracts showed decreased MD and RD in the W-NP group compared to the Wo-NP group. Using TBSS, both MD and RD decreased in extensive WM skeleton in the right hemisphere of the patients in the W-NP group. Additionally, in the follow-up longitudinal study, compared with patients in the Wo-NP group, patients in the W-NP group showed lower mean reduction rates of LGI of ROIs, and less increase of FA and more increases of MD, AD and RD in the extensive WM skeleton. CONCLUSIONS: These findings support the hypothesis that brain changes might correlate with NP in NMOSD patients and predict the changes related to NP over time.

[Evidence mapping of clinical research on 28 Chinese patent medicines for tension-type headache].

In this study, the evidence mapping methodology was used to systematically retrieve and sort out the clinical research evidence of Chinese patent medicines in the treatment of tension-type headache(TTH), and to understand the distribution of evidence in this field and the basis and quality of evidence. Chinese and English articles on the 28 Chinese patent medicines for TTH, which were recorded in National Essential Medicines List(2018), Medicine Catalogue for National Basic Medical Insurance, Work Injury Insurance, and Maternity Insurance(2020), and Chinese Pharmacopoeia(2020), were retrieved from China National Knowledge Infrastructure(CNKI), Wanfang, VIP, China Biology Medicine disc(CBMdisc), PubMed, EMbase, and Cochrane Library from the establishment to June 2021, followed by descriptive analysis. Then, tables and bubble charts were plotted to analyze the distribution characteristics of evidence. A total of 129 eligible articles were yielded: 126 randomized/non-randomized controlled trials, and 3 systematic reviews. The functions, indications, and composition of the 28 medicines, as well as the proportion of related articles, publication trends, intervention measures, and outcome indicators were compared and analyzed. The results showed that the 28 Chinese patent medicines, composed of 128 Chinese medicinals, can be classified into six categories in terms of function: reinforcing healthy Qi, tranquilizing mind, dispelling stasis, regulating Qi, treating wind, and resuscitating. There are ongoing efforts to study the treatment of TTH with Chinese patent medicine in China, despite of little evidence. The clinical positioning of Chinese patent medicine for TTH is not clear, and clinical research fails to highlight the advantages of Chinese medicine. In addition, the outcome indicators have not been standardized and unified, and there is a lack of evidence on the long-term efficacy of Chinese patent medicine for TTH. This study is the first exploratory application of evidence maps to compare the characteristics and clinical research progress of 28 Chinese patent medicines for TTH, which can provide a reference for research on the optimization of Chinese medicine strategies for TTH.

Subcortical structural abnormalities in female neuromyelitis optica patients with neuropathic pain.

Neuromyelitis optica (NMO) is a disease characterised by severe relapses of optic neuritis and longitudinally extensive transverse myelitis and it has a strong female predilection. Pain is one of the most typical symptom in NMO. However, few studies have been conducted to examine the neuropathic pain mechanism of NMO patients or gender-specific effects using magnetic resonance imaging technique. A total of 38 female patients with NMO, 28 with pain (NMOWP) and 10 without pain (NMOWoP), were classified using the Brief Pain Inventory (BPI); 22 healthy females were also recruited. We used the FSL Image Registration and Segmentation Toolbox (FIRST) for subcortical region volumes quantifications, and voxel-based morphometry analysis for cortical gray matter (GM) volume, to examine the brain morphology in NMOWP patients. In addition, correlation test between structural measurements of NMO patients and clinical indexes was also performed. The results showed: 1) no significant differences in cortical GM density between the NMOWP and NMOWoP groups; 2) significantly smaller hippocampus and pallidum volumes in the NMOWP group compared with the NMOWoP group; 3) significant negative correlation between the average BPI and volumes of the accumbens nucleus and thalamus in NMO patients. These results revealed that structural abnormality exists in NMO female patients who have pain, with significant implications for our understanding of the brain morphology in NMO patients with pain.

Decreased mRNA Expressions of CD40L in Patients with Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease that preferentially affects central nerve system. Herein, we evaluated changes of CD40L and CD40 mRNA expressions in NMOSD and controls to explore their potential roles in development of NMOSD. The expressions of CD40L and CD40 mRNA in peripheral blood mononuclear cells (PBMCs) from patients with NMOSD and healthy controls were detected by quantitative real-time PCR (qPCR). Kruskal-Wallis tests were used to compare expression levels of CD40L and CD40 mRNA between groups, and Spearman correlation analysis was performed to evaluate correlation between mRNA expression levels and annual relapse rate (ARR) of NMOSD. A total of 71 patients with NMOSD and 42 gender- and age-matched healthy volunteers were recruited in our study. Compared with healthy controls, expression of CD40L mRNA was significantly decreased in untreated patients with NMOSD, and similar trends were observed also in CD40 mRNA expression although the difference was not significant. Other than that, immunosuppressants not only successfully increased CD40L and CD40 mRNA levels during remission of NMOSD, but also corrected the negative correlation between CD40L mRNA expression and annual relapse rate (ARR) of patients NMOSD. These results favored the long-term prognosis of NMOSD patients. Our results suggest that decreased expressions of CD40L mRNA may be involved in developing of NMOSD and the proper CD40L mRNA levels benefit to prevent attacks of NMOSD. Nevertheless, the relationship between protein and mRNA expressions of CD40L and their underlying roles in the pathogenesis of NMOSD remains to be further studied.

Translation, cross-cultural adaptation, and validation of the chinese version of the 15-item myasthenia gravis quality of life questionnaire.

INTRODUCTION: We sought to translate, cross-culturally adapt, and evaluate the internal consistency and validity of the Chinese version of the 15-Item Myasthenia Gravis Quality of Life (MG-QOL15). METHODS: Translation and cross-cultural adaptation of the MG-QOL15 were performed. We used Cronbach's α to test internal consistency, one-way analysis of variance to test construct validity, and Pearson or Spearman correlations to test discriminant and concurrent validity. RESULTS: We enrolled 168 outpatients. Internal consistency was excellent (Cronbach's α = 0.928). The MG-QOL15 discriminated MG severity as stratified by the MG Composite (MGC; P < 0.001) and Osserman class (P = 0.01). Concurrent validity was low to moderate with the subscales of the 36-item Short Form (-0.31 to ∼-0.59), MGC (r = 0.46), and Myasthenia Gravis Activities of Daily Living profile (r = 0.54). DISCUSSION: The Chinese MG-QOL15 showed comparable construct, discriminant and concurrent validity, and internal consistency with to the original version. Muscle Nerve 59:95-99, 2019.

Association of GTF2IRD1-GTF2I polymorphisms with neuromyelitis optica spectrum disorders in Han Chinese patients.

Variants at the GTF2I repeat domain containing 1 (GTF2IRD1)-GTF2I locus are associated with primary Sjögren's syndrome, systemic lupus erythematosus, and rheumatoid arthritis. Numerous studies have indicated that this susceptibility locus is shared by multiple autoimmune diseases. However, until now there were no studies of the correlation between GTF2IRD1-GTF2I polymorphisms and neuromyelitis optica spectrum disorders (NMOSD). This case control study assessed this association by recruiting 305 participants with neuromyelitis optica spectrum disorders and 487 healthy controls at the Department of Neurology, from September 2014 to April 2017. Peripheral blood was collected, DNA extracteds and the genetic association between GTF2IRD1-GTF2I polymorphisms and neuromyelitis optica spectrum disorders in the Chinese Han population was analyzed by genotyping. We found that the T allele of rs117026326 was associated with an increased risk of neuromyelitis optica spectrum disorders (odds ratio (OR) = 1.364, 95% confidence interval (CI) 1.019-1.828; P = 0.037). This association persisted after stratification analysis for aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) positivity (OR = 1.397, 95% CI 1.021-1.912; P = 0.036) and stratification according to coexisting autoimmune diseases (OR = 1.446, 95% CI 1.072-1.952; P = 0.015). Furthermore, the CC genotype of rs73366469 was frequent in AQP4-IgG-seropositive patients (OR = 3.15, 95% CI 1.183-8.393, P = 0.022). In conclusion, the T allele of rs117026326 was associated with susceptibility to neuromyelitis optica spectrum disorders, and the CC genotype of rs73366469 conferred susceptibility to AQP4-IgG-seropositivity in Han Chinese patients. The protocol was approved by the Ethics Committee of West China Hospital of Sichuan University, China (approval number: 2016-31) on March 2, 2016.

Increased expression of the membrane-bound CD40 ligand on peripheral CD4+ T cells in the acute phase of AQP4-IgG-seropositive neuromyelitis optica spectrum disorders.

Currently, no data are available regarding the expression levels of CD40L on CD4+ T cells in patients with neuromyelitis optica spectrum disorders (NMOSD). The percentage of circulating CD40L+CD4+ T cells was measured by flow cytometry in 23 NMOSD patients and 10 healthy controls. The ratio of CD40L+CD4+ to CD4+ T cells in patients at acute phase (18.28 ±â€¯15.56%) was significantly higher than that in healthy controls (7.23 ±â€¯5.94%, P = .032) and was positively correlated with disease severity (r = 0.532, P = .041). Thus, our results suggest an important role of this molecule in acute attacks of NMOSD.

Pain during the acute phase of Guillain-Barré syndrome.

In this study, we tried to describe the characteristics of pain and explore the association between the incidence of pain and abnormal laboratory test results in patients during the acute phase of Guillain-Barré syndrome (GBS).This retrospective cohort study enrolled 252 patients with GBS who were in the acute phase of the disease. We collected data regarding the location and type of pain, the onset time, clinical variables and laboratory tests, including the levels of uric acid (UA), albumin, cerebrospinal fluid protein (CSFP), cerebrospinal fluid glucose (CSFG), fasting glucose upon admission, and blood creatinine. The pain descriptors were compared to the severity of disease and laboratory examination results.Around 34.5% of the patients reported pain during the acute phase of GBS. Pain was negatively correlated with the disease severity during the acute phase. In total, 29 of the 87 (33.3%) patients reported pain during the 2 weeks preceding the onset of weakness. The concentration of CSFP was positively associated with the incidence of pain, while the concentrations of UA and albumin were not correlated with the incidence of pain.We found that 33.3% of the GBS patients experienced pain within 2 weeks of onset, and the pain was positively associated with CSFP concentration but was not correlated with disease severity.

Associations between tumor necrosis factor-α gene polymorphisms and the risk of Guillain-Barré syndrome and its subtypes: A systematic review and meta-analysis.

This meta-analysis aimed to assess the relationship between tumor necrosis factor-α (TNF-α) polymorphisms and Guillain-Barré syndrome (GBS) or its subtypes of acute inflammatory demyelinating polyneuropathy (AIDP), acute motor axonal neuropathy (AMAN), and acute motor-sensory axonal neuropathy (AMSAN). A total of six studies with 1013 cases and 1029 controls were included. Our pooled data indicated that TNF-α 308G/A polymorphism was significantly associated with GBS, AMAN, and AMSAN but not with AIDP; TNF-α 857C/T polymorphism was significantly associated with AMAN but not with GBS or AIDP. Besides, no association was found between TNF-α 238G/A and 863C/A polymorphisms and GBS or its subtypes.

Association of TNFSF4 Polymorphisms with Neuromyelitis Optica Spectrum Disorders in a Chinese Population.

The tumor necrosis factor ligand superfamily member 4 (TNFSF4) gene encodes a vital co-stimulatory molecule of the immune system and has been identified as a susceptibility locus for systemic lupus erythematosus, systemic sclerosis, and primary Sjögren's syndrome. However, the association of TNFSF4 polymorphisms with neuromyelitis optica spectrum disorders (NMOSD), an inflammatory, demyelinating autoimmune disease of the central nervous system, has not yet been investigated. To evaluate whether TNFSF4 polymorphisms contribute to risk of NMOSD, four single-nucleotide polymorphisms (SNPs) (rs1234315, rs2205960, rs704840, and rs844648) were selected and genotyped in a cohort of 312 patients with NMOSD and 487 healthy controls. Our study showed that rs844648 was associated with an increased risk of NMOSD, according to the allelic model (OR = 1.30, 95% CI 1.06-1.59, P = 0.011, Pcorr = 0.044). Significant associations of rs844648 (OR = 1.67, 95% CI 1.17-2.38, P = 0.005, Pcorr = 0.02) and rs704840 (OR = 1.75, 95% CI 1.17-2.63, P = 0.007, Pcorr = 0.027) with NMOSD occurrence were also observed under the recessive model. Moreover, linkage disequilibrium analysis revealed two blocks within TNFSF4; in one block, the haplotype Ars844648Grs704840 significantly increased the risk of NMOSD, whereas Grs844648Trs704840 reduced the risk. This study demonstrates an association between TNFSF4 polymorphisms and susceptibility for the development of NMOSD in the Chinese population.

Painful tonic spasm in neuromyelitis optica spectrum disorders: Prevalence, clinical implications and treatment options.

BACKGROUND: Painful tonic spasm (PTS) is a common symptom in patients with neuromyelitis optica spectrum disorders (NMOSD). This study aimed to obtain further insights into the prevalence, characteristics, and treatment of PTS in patients with NMOSD, and to systematically investigate and compare the clinical features and prognosis of NMOSD with and without PTS. METHODS: We reviewed the medical records and prospectively interviewed patients with NMOSD who attended the West China Hospital of Sichuan University in Chengdu, China between September 2014 and December 2016. RESULTS: In total, 52 of the 230 patients with NMOSD experienced PTS (22.61%). Patients with NMOSD and PTS were characterized by a higher age at onset (P = 0.017), higher annual relapse rate (ARR) (P = 0.003), higher ARR of myelitis (P = 0.011), and a tendency to experience pruritus (P = 0.025). Sodium channel blocking antiepileptic drugs (carbamazepine or oxcarbazepine) had higher efficacy than gabapentin in the treatment of PTS (P = 0.001). Although the progression index was higher in patients with PTS, this difference did not reach statistical significance (P = 0.05). CONCLUSIONS: Our study suggested that immunosuppressors for the prevention of relapse should be administered without delay in patients with NMOSD and PTS. Owing to the side effects of carbamazepine, we recommend oxcarbazepine as the first-line of treatment for PTS in patients with NMOSD. Whether PTS is a marker of disease severity in NMOSD remains to be determined, requiring a long-term prospective observational study.

Muscle damage in patients with neuromyelitis optica spectrum disorder.

OBJECTIVE: Increasing evidence has shown that skeletal muscle damage plays a role in neuromyelitis optica spectrum disorder (NMOSD). The objective of this study was to compare the serum creatine kinase (sCK) levels in NMOSD patients with different clinical statuses. METHODS: In the observational study, levels of sCK were measured during the acute and stable phases for patients with NMOSD and healthy controls (HCs). RESULTS: We enrolled 168 patients with NMOSD (female:male ratio, 153:15; age: 43.9 ± 13.1 years) in the acute phase, and blood samples were collected from 85 of the patients with NMOSD during both acute and stable phases to determine the sCK levels. The mean log sCK levels of the patients with NMOSD in the acute phase were higher (4.51 ± 1.17, n = 85) than those of the patients with NMOSD in the stable phase (3.85 ± 0.81, n = 85, p = 0.000). Furthermore, the log sCK levels of the patients with NMOSD in the stable phase were lower than those of the HCs (4.31 ± 0.39, n = 200, p = 0.000). In patients with sCK levels within the normal limits, these differences were also observed (p < 0.05). In the multivariable linear regression model performed for the patients with NMOSD in the acute phase, it suggested that a higher estimated glomerular filtration rate (p = 0.026), patients with the core clinical characteristics of optic neuritis (p = 0.005), and serum anti-SSA positivity (p = 0.019) predicted lower log sCK levels. CONCLUSIONS: Muscle damage occurs in patients with NMOSD and is aggravated during the acute phase.

STAT4 Polymorphisms are Associated with Neuromyelitis Optica Spectrum Disorders.

STAT4 plays a crucial role in the functioning of the innate and adaptive immune cells and has been identified as a susceptibility gene in numerous autoimmune disorders. However, its association with neuromyelitis optica spectrum disorders (NMOSD) remains uncertain. Here, we performed a case-control study to determine whether STAT4 contributed to the risk of NMOSD. We tested five STAT4 SNPs in 233 patients with established NMOSD and 492 healthy controls. Chi-square tests and logistic regression analyses were performed with four genetic models, including allelic, additive, dominant, and recessive models, to identify associations with NMOSD. The results of multiple test comparisons were corrected using the Benjamini and Hochberg false discovery rate (FDR-BH). After correcting for multiple test comparisons, the minor alleles of four STAT4 SNPs exhibited significant association with increased risk of NMOSD (rs7574865 T, odds ratio [OR] = 1.66, 95% confidence interval [CI] 1.32-2.08, P corr = 0.000; rs10181656 G, OR = 1.62, 95% CI 1.29-2.03, P corr = 0.000; rs10168266 T, OR = 1.59, 95% CI 1.27-2.00, P corr = 0.001; and rs13426947 A, OR = 1.51, 95% CI 1.21-1.90, P corr = 0.004). Identical results were observed in the dominant, recessive, and additive models. In contrast, the G allele of rs7601754 displayed a protective effect against NMOSD (OR = 0.53, 95% CI 0.36-0.76, P corr = 0.006). Our study indicates that STAT4 polymorphisms are associated with the risk of NMOSD, which provides novel insights into the underlying mechanisms of this disease.

Association of CD58 gene polymorphisms with NMO spectrum disorders in a Han Chinese population.

This study aimed to perform a comprehensive assessment of the association between CD58 polymorphisms and the risk of neuromyelitis optica spectrum disorders (NMOSD) in a Han Chinese population. Nine single-nucleotide polymorphisms (SNPs) were genotyped in 230 NMOSD patients and 487 healthy controls. Five SNPs were significantly associated with an increased risk of NMOSD (rs2300747, rs1335532, rs56302466, rs1016140, and rs12044852). The haplotype TAGCCCAA significantly increased the risk of NMOSD, while TATTACGG reduced the risk. In conclusion, this study identified a new NMOSD susceptibility variant, rs56302466, and suggested that CD58 polymorphisms are associated with the risk of NMOSD in Han Chinese.

Association of CD40 Gene Polymorphisms with Susceptibility to Neuromyelitis Optica Spectrum Disorders.

The CD40 gene is associated with many autoimmune diseases; however, there are few studies in literatures that investigate the association between CD40 and neuromyelitis optica spectrum disorders (NMOSD). This study aimed to estimate the potential association of CD40 gene polymorphisms with susceptibility to NMOSD. Four SNPs (rs1883832, rs3765459, rs4810485, and rs6074022) were selected and genotyped in a Chinese cohort comprising 162 patients with NMOSD and 237 healthy controls. P values, odds ratios (ORs), and 95 % confidential intervals (CI) for four test models (allelic, additive, dominant, and recessive) were used to assess relationships between CD40 and NMOSD. Results showed that the rs3765459 variant was significantly associated with increased risk of NMOSD in allelic model (OR = 1.48, 95 % CI 1.10-1.98, P = 0.009, P corr = 0.037), and similar results were detected in the additive and recessive models (OR = 1.47, 95 % CI 1.09-1.97, P = 0.010, P corr = 0.042; OR = 2.12, 95 % CI 1.18-3.8, P = 0.012, P corr = 0.048, respectively). Other three SNPs showed protections on NMOSD in dominant models (rs6074022, OR = 0.64, 95 % CI 0.42-0.95, P = 0.031; rs1883832, OR = 0.65, 95 % CI 0.43-0.97, P = 0.036; and rs4810485, OR = 0.63, 95 % CI 0.42-0.95, P = 0.029, respectively), but not significantly after Bonferroni corrections for multiple tests. In addition, haplotype analysis of these SNPs in tight linkage did not reveal significant association with NMOSD. This study indicates that the rs3765459 variant in CD40 gene is associated with susceptibility to NMOSD. Larger sample size studies in other ethnicities are needed to verify this association.

Factors that impact health-related quality of life in neuromyelitis optica spectrum disorder: anxiety, disability, fatigue and depression.

AIMS: Neuromyelitis optica spectrum disorder (NMOSD) is associated with reduced health-related quality of life (HRQOL). This study aimed to investigate factors that impact HRQOL in NMOSD. METHODS: A series of questionnaires were completed by 73 patients to assess the relationships between HRQOL and fatigue, depression, anxiety and sleep disorder. We also evaluated the contributions of clinical characteristics to HRQOL. Correlation and regression analysis were conducted to identify factors that negatively impact HRQOL in NMOSD. RESULTS: Pearson's correlation analysis showed that reduced HRQOL was strongly correlated with anxiety (r=-0.77, P=0.000), fatigue (r=-0.75, P=0.000) and depression (r=-0.73, P=0.000); and moderately correlated with disability (r=-0.53, P=0.000) and sleep disorder (r=-0.59, P=0.000). Stepwise regression analysis further revealed that anxiety was the best predictor of both the global and physical composite scores of HRQOL, followed by disability, fatigue and depression (global composite, r(2)=0.76, P=0.000; physical composite, r(2)=0.71, P=0.000). Depression, fatigue and anxiety were the main predictors of the mental health composite score of HRQOL (r(2)=0.69, P=0.000). Other factors did not have an effect on HRQOL. CONCLUSIONS: This study revealed factors that impact HRQOL in NMOSD and provided the first demonstration that anxiety, disability, fatigue and depression are independent predictors of poor HRQOL in NMOSD.

RNA sequencing reveals retinal transcriptome changes in STZ-induced diabetic rats.

The present study aimed to investigate changes in retinal gene expression in streptozotocin (STZ)­induced diabetic rats using next­generation sequencing, utilize transcriptome signatures to investigate the molecular mechanisms of diabetic retinopathy (DR), and identify novel strategies for the treatment of DR. Diabetes was chemically induced in 10­week­old male Sprague­Dawley rats using STZ. Flash­electroretinography (F­ERG) was performed to evaluate the visual function of the rats. The retinas of the rats were removed to perform high throughput RNA sequence (RNA­seq) analysis. The a­wave, b­wave, oscillatory potential 1 (OP1), OP2 and ∑OP amplitudes were significantly reduced in the diabetic group, compared with those of the control group (P<0.05). Furthermore, the implicit b­wave duration 16 weeks post­STZ induction were significantly longer in the diabetic rats, compared with the control rats (P<0.001). A total of 868 genes were identified, of which 565 were upregulated and 303 were downregulated. Among the differentially expressed genes (DEGs), 94 apoptotic genes and apoptosis regulatory genes, and 19 inflammatory genes were detected. The results of the KEGG pathway significant enrichment analysis revealed enrichment in cell adhesion molecules, complement and coagulation cascades, and antigen processing and presentation. Diabetes alters several transcripts in the retina, and RNA­seq provides novel insights into the molecular mechanisms underlying DR.

[Experimental study on effect of monocyte chemoattractant protein 1 on migration of induced and differentiated mouse bone marrow mesenchymal stem cells in vitro].

OBJECTIVE: To investigate the effect of monocyte chemoattractant protein 1 (MCP-1) on the migration of the induced and differentiated mouse bone marrow mesenchymal stem cells (BMSCs) for raising the efficacy of intravenous transplantation of BMSCs. METHODS: The BMSCs were cultured with the method of differential adhesion and density gradient centrifugation of C57/BL10 mice, and were identified by alkaline phosphatase Gomori modified staining after osteogenic inducing. At the 3rd passage, the BMSCs were induced to the myoblasts with 5-azacytidine (5-Aza). The chemotaxis of MCP-1 in the induced and differentiated BMSCs in vitro at concentrations of 25, 50, 100, 200, and 400 ng/mL was observed through the migration test, by counting the number of the migrated cells. The expression of the chemokine receptor 2 (CKR-2) in the induced and differentiated BMSCs was detected with the flow cytometry. RESULTS: The cells could be cultured with the methods of differential adhesion and density gradient centrifugation and still had higher proliferative and differentiative potency; the induced cells at the 3rd passage could differentiate to the osteoblasts, confirming that the cells were BMSCs; the myogenic induced BMSCs possessed the sarcotubule structure. The number of the migrating BMSCs at MCP-1 concentrations of 25-400 ng/mL were respectively 35.066 7 +/- 6.584 2, 43.200 0 +/- 6.460 8, 44.466 7 +/- 4.823 5, 45.600 0 +/- 8.650 3, and 50.733 3 +/- 7.582 5; showing significant difference when compared with control group (28.333 3 +/- 8.917 6, P < 0.05), and presenting significant difference among 25, 50, 400 ng/mL groups compared with each other (P < 0.05). The expression of CKR-2 in the mouse BMSCs (48.0%) was significantly higher (P < 0.001) than those of blank control (0.6%) and negative control (17.0%). CONCLUSION: The results indicate that the MCP-1 can induce the migration of mouse BMSCs by MCP-1/CKR-2 pathway.