The Antioxidant Dendrobium officinale Polysaccharide Modulates Host Metabolism and Gut Microbiota to Alleviate High-Fat Diet-Induced Atherosclerosis in ApoE-/- Mice.

BACKGROUND: The discovery of traditional plants' medicinal and nutritional properties has opened up new avenues for developing pharmaceutical and dietary strategies to prevent atherosclerosis. However, the effect of the antioxidant Dendrobium officinale polysaccharide (DOP) on atherosclerosis is still not elucidated. PURPOSE: This study aims to investigate the inhibitory effect and the potential mechanism of DOP on high-fat diet-induced atherosclerosis in Apolipoprotein E knockout (ApoE-/-) mice. STUDY DESIGN AND METHODS: The identification of DOP was measured by high-performance gel permeation chromatography (HPLC) and Fourier transform infrared spectroscopy (FTIR). We used high-fat diet (HFD)-induced atherosclerosis in ApoE-/- mice as an animal model. In the DOP intervention stage, the DOP group was treated by gavage with 200 µL of 200 mg/kg DOP at regular times each day and continued for eight weeks. We detected changes in serum lipid profiles, inflammatory factors, anti-inflammatory factors, and antioxidant capacity to investigate the effect of the DOP on host metabolism. We also determined microbial composition using 16S rRNA gene sequencing to investigate whether the DOP could improve the structure of the gut microbiota in atherosclerotic mice. RESULTS: DOP effectively inhibited histopathological deterioration in atherosclerotic mice and significantly reduced serum lipid levels, inflammatory factors, and malondialdehyde (F/B) production. Additionally, the levels of anti-inflammatory factors and the activity of antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX), were significantly increased after DOP intervention. Furthermore, we found that DOP restructures the gut microbiota composition by decreasing the Firmicutes/Bacteroidota (F/B) ratio. The Spearman's correlation analysis indicated that serum lipid profiles, antioxidant activity, and pro-/anti-inflammatory factors were associated with Firmicutes, Bacteroidota, Allobaculum, and Coriobacteriaceae_UCG-002. CONCLUSIONS: This study suggests that DOP has the potential to be developed as a food prebiotic for the treatment of atherosclerosis in the future.

MX1 and UBE2L6 are potential metaflammation gene targets in both diabetes and atherosclerosis.

Background: The coexistence of diabetes mellitus (DM) and atherosclerosis (AS) is widespread, although the explicit metabolism and metabolism-associated molecular patterns (MAMPs) responsible for the correlation are still unclear. Methods: Twenty-four genetically wild-type male Ba-Ma mini pigs were randomly divided into five groups distinguished by different combinations of 90 mg/kg streptozotocin (STZ) intravenous injection and high-cholesterol/lipid (HC) or high-lipid (HL) diet feeding for 9 months in total. Pigs in the STZ+HC and STZ+HL groups were injected with STZ first and then fed the HC or HL diet for 9 months. In contrast, pigs in the HC+STZ and HL+STZ groups were fed the HC or HL diet for 9 months and injected with STZ at 3 months. The controls were only fed a regular diet for 9 months. The blood glucose and abdominal aortic plaque observed through oil red O staining were used as evaluation indicators for successful modelling of DM and AS. A microarray gene expression analysis of all subjects was performed. Results: Atherosclerotic lesions were observed only in the HC+STZ and STZ+HC groups. A total of 103 differentially expressed genes (DEGs) were identified as common between them. The most significantly enriched pathways of 103 common DEGs were influenza A, hepatitis C, and measles. The global and internal protein-protein interaction (PPI) networks of the 103 common DEGs consisted of 648 and 14 nodes, respectively. The top 10 hub proteins, namely, ISG15, IRG6, IRF7, IFIT3, MX1, UBE2L6, DDX58, IFIT2, USP18, and IFI44L, drive aspects of DM and AS. MX1 and UBE2L6 were the intersection of internal and global PPI networks. The expression of MX1 and UBE2L6 was 507.22 ± 342.56 and 96.99 ± 49.92 in the HC+STZ group, respectively, which was significantly higher than others and may be linked to the severity of hyperglycaemia-related atherosclerosis. Further PPI network analysis of calcium/micronutrients, including MX1 and UBE2L6, consisted of 58 and 18 nodes, respectively. The most significantly enriched KEGG pathways were glutathione metabolism, pyrimidine metabolism, purine metabolism, and metabolic pathways. Conclusions: The global and internal PPI network of the 103 common DEGs consisted of 648 and 14 nodes, respectively. The intersection of the nodes of internal and global PPI networks was MX1 and UBE2L6, suggesting their key role in the comorbidity mechanism of DM and AS. This inference was partly verified by the overexpression of MX1 and UBE2L6 in the HC+STZ group but not others. Further calcium- and micronutrient-related enriched KEGG pathway analysis supported that MX1 and UBE2L6 may affect the inflammatory response through micronutrient metabolic pathways, conceptually named metaflammation. Collectively, MX1 and UBE2L6 may be potential common biomarkers for DM and AS that may reveal metaflammatory aspects of the pathological process, although proper validation is still needed to determine their contribution to the detailed mechanism.

Intelligent diagnosis of retinal vein occlusion based on color fundus photographs.

AIM: To develop an artificial intelligence (AI) diagnosis model based on deep learning (DL) algorithm to diagnose different types of retinal vein occlusion (RVO) by recognizing color fundus photographs (CFPs). METHODS: Totally 914 CFPs of healthy people and patients with RVO were collected as experimental data sets, and used to train, verify and test the diagnostic model of RVO. All the images were divided into four categories [normal, central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), and macular retinal vein occlusion (MRVO)] by three fundus disease experts. Swin Transformer was used to build the RVO diagnosis model, and different types of RVO diagnosis experiments were conducted. The model's performance was compared to that of the experts. RESULTS: The accuracy of the model in the diagnosis of normal, CRVO, BRVO, and MRVO reached 1.000, 0.978, 0.957, and 0.978; the specificity reached 1.000, 0.986, 0.982, and 0.976; the sensitivity reached 1.000, 0.955, 0.917, and 1.000; the F1-Sore reached 1.000, 0.955 0.943, and 0.887 respectively. In addition, the area under curve of normal, CRVO, BRVO, and MRVO diagnosed by the diagnostic model were 1.000, 0.900, 0.959 and 0.970, respectively. The diagnostic results were highly consistent with those of fundus disease experts, and the diagnostic performance was superior. CONCLUSION: The diagnostic model developed in this study can well diagnose different types of RVO, effectively relieve the work pressure of clinicians, and provide help for the follow-up clinical diagnosis and treatment of RVO patients.

Measurement method of tear meniscus height based on deep learning.

Tear meniscus height (TMH) is an important reference parameter in the diagnosis of dry eye disease. However, most traditional methods of measuring TMH are manual or semi-automatic, which causes the measurement of TMH to be prone to the influence of subjective factors, time consuming, and laborious. To solve these problems, a segmentation algorithm based on deep learning and image processing was proposed to realize the automatic measurement of TMH. To accurately segment the tear meniscus region, the segmentation algorithm designed in this study is based on the DeepLabv3 architecture and combines the partial structure of the ResNet50, GoogleNet, and FCN networks for further improvements. A total of 305 ocular surface images were used in this study, which were divided into training and testing sets. The training set was used to train the network model, and the testing set was used to evaluate the model performance. In the experiment, for tear meniscus segmentation, the average intersection over union was 0.896, the dice coefficient was 0.884, and the sensitivity was 0.877. For the central ring of corneal projection ring segmentation, the average intersection over union was 0.932, the dice coefficient was 0.926, and the sensitivity was 0.947. According to the evaluation index comparison, the segmentation model used in this study was superior to the existing model. Finally, the measurement outcome of TMH of the testing set using the proposed method was compared with manual measurement results. All measurement results were directly compared via linear regression; the regression line was y0.98x-0.02, and the overall correlation coefficient was r 20.94. Thus, the proposed method for measuring TMH in this paper is highly consistent with manual measurement and can realize the automatic measurement of TMH and assist clinicians in the diagnosis of dry eye disease.

Autophagy triggers endoplasmic reticulum stress and C/EBP homologous protein-mediated apoptosis in OGD/R-treated neurons in a caspase-12-independent manner.

We reported that a high level of autophagy was initiated by oxygen-glucose deprivation (OGD) and was maintained in neurons even after oxygen-glucose deprivation followed by reoxygenation (OGD/R), accompanied by neuronal apoptosis. This study focused on autophagy-induced apoptosis and its signaling network, especially the role of endoplasmic reticulum stress (ERS). Analysis of primary cultured cortical neurons from mice showed that the autophagy-induced apoptosis depended on caspase-8 and -9 but not on caspase-12. This finding did not mean that the endoplasmic reticulum did not participate in this process. Increases in the levels of endoplasmic reticulum (ER) biomarkers and binding immunoglobulin protein (BiP) were induced by autophagy in OGD/R-treated neurons. In addition, as an apoptotic transcription factor induced by ER stress, C/EBP homologous protein (CHOP) expression was significantly increased in neurons after OGD/R. This result suggested that the autophagy-BiP-CHOP-caspase (8 and 9)-dependent apoptotic signaling pathway at least partly participated in autophagy-induced apoptosis in primary cortical neurons. It revealed that ER induced apoptosis in neurons suffering from OGD/R injury in an ER stress-CHOP-dependent manner rather than a caspase-12-dependent manner. However, more research on signaling or cross-linking networks and intermediate links is needed. The realization of caspase-12-independent BiP-CHOP neuronal apoptosis pathway has expanded our understanding of the neuronal apoptosis network, which may eventually provide endogenous interventional strategies for OGD/R injury after stroke.NEW & NOTEWORTHY ER stress induced by autophagy mediates caspase-8- and caspase-9-dependent apoptosis pathways by regulating CHOP in neurons exposed to OGD/R. We hypothesized that the autophagy-BiP-CHOP-caspase (8 and 9)-dependent apoptotic signaling pathway at least partly participated in autophagy-induced apoptosis in primary cortical neurons.

Predictive Value of Cerebrospinal Fluid Biomarkers for Tap Test Responsiveness in Patients With Suspected Idiopathic Normal Pressure Hydrocephalus.

Background: The value of cerebrospinal fluid (CSF) biomarkers for assessing idiopathic normal pressure hydrocephalus (iNPH) must be determined. This prospective study aimed to reveal the correlation between CSF biomarkers and clinical symptoms of iNPH and the predictive value of these biomarkers for tap test responsiveness. Methods: Thirty-nine patients with suspected iNPH were recruited, contributed qualified CSF, and underwent a tap test and unified pre- and post-test evaluations of the neurological function. Results: The analysis of biomarkers from the patients' CSF showed decreased levels of tau and its phosphorylated form, especially in the tap test (+) group. The responsiveness of the tap test was also related to the number of combined symptoms (p < 0.01), and a correlation was found between the end pressure or pressure difference in CSF and tap test responsiveness (p < 0.05). The results of the binary logistic regression analysis showed that P (tap test responsiveness) = 1/1 + e∧ - (-5.505 + 55.314 * ratio of p/T-tau - 1.586 * numbers of combined symptoms). The combined indicators (-5.505 + 0.553 * percentage of p/T-tau - 1.586 * numbers of combined symptoms) resulted in the highest sensitivity and specificity of 94.12% and 72.73%, respectively. Conclusions: CSF biomarkers may be assessed to judge tap test responsiveness, which is beneficial for the feasibility of a clinical application.

Synergistic Improvement in Children with Cerebral Palsy Who Underwent Double-Course Human Wharton's Jelly Stem Cell Transplantation.

BACKGROUND: Our previous studies confirmed that human Wharton's Jelly stem cell (hWJSC) transplantation improved motor function in children with spastic cerebral palsy (CP). This study investigated the dose-effect relationship between the transplanted cell dosage and efficacy in CP children. METHODS: CP children who received one- or two-course (four or eight times lumbar puncture, 4 or 8 × 107 hWJSCs) cell therapy were recruited into this study. Assessments of motor function were performed according to scales for gross motor function measurement (GMFM) and fine motor function measurement (FMFM). The measurement data obtained in the two different groups were analyzed by t-test. Univariate repeated measures analysis of variance was used to compare the data obtained at baseline and 6 or 12 months posttransplantation and met the conditions for Mauchly's sphericity test. RESULTS: The results for fifty-seven pediatric CP patients (including 35 male and 22 female patients) who completed follow-up showed that gross and fine motor functions improved after cell therapy. Interestingly, the GMFM and FMFM scores in patients who received one course of transplantation were significantly increased at 6 months after treatment. Moreover, another course of transplantation further improved gross and fine motor function in children. The scores for GMFM and FMFM were significantly higher at 6 months posttransplantation than at baseline and showed a linear upward trend. There was no gender difference in GMFM. Interestingly, there was a significant difference between male and female patients in the B and C dimensions of FMFM. These results reveal a gender-related susceptibility to stem cell therapy, especially for movement capability of the upper extremity joint and grasping ability. Similarly, in the group aged ≤3 years old, the improvement observed in dimension A (lying and rolling) of GMFM was nearly exponential and showed a quadratic trend. The results for FMFM were similar to those for GMFM. Moreover, the improvement in motor function was not age dependent. CONCLUSIONS: In this study, our data collectively reveal that CP children display sex- or age-dependent responses to hWJSC therapy; these results shed light on the clinical utility of this approach in specific populations.

Phosphorylated mTORC1 represses autophagic-related mRNA translation in neurons exposed to ischemia-reperfusion injury.

OBJECTIVES: The sequential reactivation of mechanistic target of rapamycin (mTOR) inhibited autophagic flux in neurons exposed to oxygen-glucose deprivation/reperfusion (OGD/R), which was characterized by reduction of autophagosome formation and restriction of autolysosome degradation. However, its detailed molecular mechanism was still unknown. In this study, we further explore the existing form of mTOR and its suppression on the transcriptional levels of related mRNA from neurons exposed to ischemia-reperfusion injury. METHODS: The OGD/R or middle cerebral artery occlusion/reperfusion (MCAO/R)-treated neurons was used to simulate ischemia/reperfusion injury . Autophagy flux was monitored by means of microtubule-associated protein 1 light chain 3 (LC3) and p62. The reactivation of mTOR was determined by phosphorylation of ribosomal protein S6 kinase 1 (S6K1). Then the inhibitors of mTOR were used to confirm its existence form. Finally, the mRNA transcription levels were analyzed to observe the negative regulation of mTOR. RESULTS: The sequential phosphorylation of mTOR contributed to the neuronal autophagy flux blocking. mTOR was re-phosphorylated and existed as mTOR complex 1 (mTORC1), which was supported by phosphorylation of S6K1 at Thr 389 in neurons. In addition, the phosphorylation of S6K1 was decreased roughly by applying mTORC1 inhibitors, rapamycin and torin 1. However, the administration of mTORC1/2 inhibitor PP242 could recover the phosphorylation of S6K1, which suggested that mTORC2 was involved in the regulation of mTORC1 activity. In paralleling with reactivation of mTORC1, related mRNA transcription was repressed in neurons under ischemia-reperfusion exposure in vivo and in vitro. The mRNA expression levels of LC3, Stx17, Vamp8, Snap29, Lamp2a, and Lamp2b were decreased in neurons after reperfusion, comparing with ischemia-treated neurons. CONCLUSIONS: The reactivated mTORC1 could suppress the transcription levels of related mRNA, such as LC3, Stx17, Vamp8, Snap29, Lamp2a, and Lamp2b. The research will expand the horizons that mTOR would negatively regulate autophagy at transcription and post-translation levels in neurons suffering ischemia-reperfusion injury.

cPKCγ-Modulated Sequential Reactivation of mTOR Inhibited Autophagic Flux in Neurons Exposed to Oxygen Glucose Deprivation/Reperfusion.

We have reported that conventional protein kinase Cγ (cPKCγ)-modulated neuron-specific autophagy improved the neurological outcome of mice following ischemic stroke through the Akt-mechanistic target of rapamycin (mTOR) pathway. However, its detailed molecular mechanism remains unclear. In this study, primary cortical neurons from postnatal one-day-old C57BL/6J cPKCγ wild-type (cPKCγ+/+) and knockout (cPKCγ−/−) mice suffering oxygen glucose deprivation/reperfusion (OGD/R) were used to simulate ischemia/reperfusion injury in vitro. A block of autophagic flux was observed in cPKCγ+/+ neurons under OGD/R exposure, characterized by accumulation of p62. Immunofluorescent results showed a decrease in colocalization between LC3 and Atg14 or Stx17 in cPKCγ+/+ neurons when compared with cPKCγ−/− neurons after OGD/R. However, the colocalization between LC3 and Lamp2 was barely decreased, indicating the presence of autolysosomes. The larger lysotracker-positive structures were also significantly increased. These results suggest that cPKCγ-induced inhibition of autophagy occurred at the stages of autophagosome formation, Stx17 anchoring, and the degradation of autolysosomes in particular. In addition, cPKCγ-modulated phosphorylation of mTOR at Ser 2481 was dependent on the site of Ser 2448, which may have blocked autophagic flux. cPKCγ-modulated sequential reactivation of mTOR inhibited autophagic flux in neurons exposed to OGD/R, which may provide endogenous interventional strategies for stroke, especially ischemia/reperfusion injury.

Determination of Brain-Regional Blood Perfusion and Endogenous cPKCγ Impact on Ischemic Vulnerability of Mice with Global Ischemia.

Conventional protein kinase C (cPKC)γ participated in cerebral hypoxic preconditioning-induced neuroprotection and affected the neurological outcome of ischemic stroked mice. As an independent predictor of ischemic stroke, the internal carotid artery occlusion (ICAO)-caused brain-regional ischemic injury may worsen the neurological outcome of patients. However, the brain-regional ischemic vulnerability and its underlying mechanism remain unclear. In this study, the bilateral ICAO (BICAO) model was applied in cPKCγ wild type (WT) and knockout (KO) mice to determine the cPKCγ impact on brain-regional ischemic vulnerability. The arterial spin labeling (ASL) imaging results showed that 7 days BICAO-induced global ischemia could cause significant blood perfusion loss in prefrontal cortex (69.13%), striatum (61.69%), hypothalamus (67.36%), hippocampus (69.82%) and midbrain (40.53%) of WT mice, along with neurological deficits. Nissl staining and Western blot results indicated that hypothalamus and midbrain had more severe neural cell loss than prefrontal cortex, striatum and hippocampus, which negatively coincided with endogenous cPKCγ protein levels but not blood perfusion loss and cPKCγ membrane translocation levels. Furthermore, we found that cPKCγ KO significantly aggravated the neuron loss in prefrontal cortex, striatum and hippocampus and abolish the regional ischemic vulnerability by using immunofluorescent staining with neuron-specific marker NeuN. Similarly, cPKCγ KO also significantly increased Caspase-3, -8 and -9 cleavage levels in prefrontal cortex, striatum, hippocampus, hypothalamus and midbrain of mice with 24 h BICAO. These results suggested that hypothalamus and midbrain are more vulnerable to ischemia, and endogenous cPKCγ affects the regional ischemic vulnerability through modulating Caspase-8 and -9 dependent cell apoptosis.

Nitric oxide-mediated pathways and its role in the degenerative diseases.

Nitric oxide (NO) is a relatively short-lived inorganic free radical, which can be produced by different types of cells in multi-cellular organisms. This diffusible messenger functions as either an effector or a second messenger in many intercellular communications or intracellular signaling pathways. NO becomes noxious if it is produced in excess. These effects are mainly mediated by the reactivity of NO with various reactive oxygen species, which can be countered by antioxidant enzymes. In addition, NO can directly modify biological molecules via S-nitrosylation and lead to altered signaling responses. Accumulating evidence suggests that NO has a double-edged role in a dose-dependent, cell-type specific, and biological milieu-dependent way. In the present review, we summarized the synthesis and signaling pathway of NO, and especially focused on its involvement in biological processes, such as endoplasmic reticulum stress, apoptosis and autophagy. Besides, we discussed the functions of NO in the nervous system and its potential role in neurodegenerative diseases. We proposed the target on NO may shed light on the treatment of the related diseases.

Autophagy in long propriospinal neurons is activated after spinal cord injury in adult rats.

Spinal cord injury (SCI) is a common disease worldwide that causes permanent neuronal dysfunction without an effective treatment. Long propriospinal neurons (LPSNs) that are spared from injury play a key role in spontaneous recovery after SCI. Traumatic injury of the central nervous system can activate autophagy, which could be a target in the development of a new therapeutic strategy to prevent neuronal loss. Our research focused on whether autophagy is involved in the loss of LPSNs after introducing spinal cord injury in adult rats. Different sacrifice time points were chosen to characterize autophagy and apoptosis. Autophagy and a blocked autophagy flux reached their peaks at 3 d after injury, while apoptosis reached its peak at 7 d after injury when the number of LPSNs significantly decreased. Both autophagy and apoptosis contributed to the loss of LPSNs, and apoptosis was the main cause of cell death. However, autophagy may prevent programmed LPSN cell death (apoptosis), which could promote cell survival.

Evaluation of Somatosensory Evoked Potential and Pain Rating Index in a Patient with Spinal Cord Injury Accepted Cell Therapy.

UNLABELLED: Spinal cord injury (SCI) causes a high incidence of motor and sensory dysfunctions accompanied with neuropathic pain. No effective treatment is available. Both somatosensory evoked potential (SSEP) and neuropathic pain (NPP) are transmitted via myelinated large diameter fibers of deep sensory pathways. Here we aimed to evaluate whether SSEP can consistently and objectively assess transmission of deep sensory pathways, and to examine the effects of umbilical cord mesenchymal stem cell (UCMSC) transplantation on SSEP and NPP as assessed by the pain rating index (PRI) in a patient with a 2-year history of complete cervical SCI. We demonstrate that SSEP can directly reflect physiological function of myelinated large fibers in deep sensory pathway transmission (NPP is also transmitted by the same pathway). One year after UCMSC transplantation, the SSEP parameter, PRI, and clinical presentations of NPP significantly improved. KEY WORDS: Spinal cord, neuropathic pain, somatosensory evoked potential, umbilical cord mesenchymal stem cells.

The hetero-transplantation of human bone marrow stromal cells carried by hydrogel unexpectedly demonstrates a significant role in the functional recovery in the injured spinal cord of rats.

Spinal cord injury (SCI) often causes a disturbance in the microenvironment in the lesion site resulting in sudden loss of sensory and motor function. Transplantation of stem cells provides a promising strategy in the treatment of SCI. But limited growth and immunological incompatibility of the stem cells with the host limits the application of this strategy. In order to get better survival and integration with the host, we employed a hyaluronic acid (HA) based scaffold covalently modified by poly-l-Lysine (PLL) as a vehicle to deliver the human bone marrow stromal cells (BMSCs) to the injured spinal cord of rats. The BMSCs were chosen as an ideal candidate for its advantage of low expression of major histocompatibility complex II. The data unexpectedly showed that the hetero-transplanted cells survived well in the lesion site even at 8 weeks post injury. Both the immunofluorescent and the electrophysiological assay indicated better survival of the transplanted cells and improved axonal growth in SCI rats transplanted with BMSCs in HA-PLL in contrast to the groups without either BMSCs or the HA scaffold transplantation. These promotions may account for the functional recovery assessed by Basso-Beattie-Bresnahan (BBB) locomotor rating scale in the HA-PLL seeded with BMSCs group. These data suggests that hetero-transplantation of human BMSCs delivered by HA scaffold demonstrates a significant role in the functional recovery in the injured spinal cord of rats.

Effect of umbilical cord mesenchymal stromal cells on motor functions of identical twins with cerebral palsy: pilot study on the correlation of efficacy and hereditary factors.

BACKGROUND AIMS: The objective of this study was to compare the impact of umbilical cord-derived mesenchymal stromal cell (UCMSC) transplantation on the motor functions of identical twins with cerebral palsy (CP) and to analyze the correlation between the efficacy and hereditary factors. METHODS: Eight pairs (16 individuals) of identical twins with CP were recruited and received allogenic UCMSC transplantation by means of subarachnoid injection. The gross motor function measure (GMFM) and the fine motor function measure (FMFM) were performed before and 1 and 6 months after the treatment to analyze the results of individuals before and after the therapy, between two individuals of an identical twin and among twin pairs. Repeated-measured data variance was used to analyze the GMFM and FMFM scores of patients before and 1 and 6 months after the therapy. RESULTS: Eight pairs (16 individuals) of children with CP had significant improvement in the GMFM at the end of the 1st and 6th months after the therapy compared with that before the therapy, whereas the amelioration of the FMFM was not statistically significant. The improvements in motor functions between two individuals of an identical twin but not among twin pairs were correlated. CONCLUSIONS: UCMSC transplantation significantly improves GMFM in children with CP; motor function improvements in the GMFM between two individuals of an identical twin were closely correlated, but improvements among twin pairs were not correlated. We hypothesize that hereditary factors contribute to the mechanisms of UCMSC transplantation in motor function improvement in children with CP.

Clinical observation of umbilical cord mesenchymal stem cell transplantation in treatment for sequelae of thoracolumbar spinal cord injury.

BACKGROUND: Umbilical cord mesenchymal stem cells (UCMSCs) have a considerable advantage and potential in treating for central nervous system diseases and have become a novel alternative treatment for spinal cord injury. This study aims to compare the neurological function outcome of stem cell transplantation, rehabilitation therapy, and self-healing for sequelae of spinal cord injury. METHODS: Thirty-four cases of thoracolumbar spinal cord injury were randomly divided into three groups: the stem cell transplantation group was given CT-guided UCMSC transplantation twice; the rehabilitation group received rehabilitation therapy; and the blank control group did not receive any specific treatment. AIS grading, ASIA scoring, the manual muscle strength and muscle tension scale, and the Barthel index were used to evaluate the clinical outcome. Urodynamic examination was also performed for patients in the UCMSC group and the rehabilitation therapy group. RESULTS: Seven of the ten patients in the UCMSC group had significant and stable improvement in movement, self-care ability, and muscular tension; five of the forteen patients (36%) in the rehabilitation group also had certain improvement in these aspects. Urodynamic examination demonstrated that patients in the UCMSC group exhibited an increase in maximum urinary flow rate and maximum bladder capacity, as well as a decrease in residue urine volume and maximum detrusor pressure. The rehabilitation group exhibited decreased maximum bladder capacity, but no perceptible change in maximum urinary flow rate, residue urine volume or maximum detrusor pressure. CONCLUSIONS: UCMSC transplantation can effectively improve neurological functional recovery after spinal cord injury, and its efficacy is superior to that of rehabilitation therapy and self-healing. TRIAL REGISTRATION: The present clinical study was registered at chictr.org (registration number: NCT01393977).

A preliminary evaluation of efficacy and safety of Wharton's jelly mesenchymal stem cell transplantation in patients with type 2 diabetes mellitus.

INTRODUCTION: Stem cell therapy has recently been introduced to treat patients with type 2 diabetes mellitus (T2DM). However, no data are available on the efficacy and safety of allogeneic Wharton's Jelly-derived mesenchymal stem cell (WJ-MSC) transplantation in patients with T2DM. Here we performed a non-placebo controlled prospective phase I/II study to determine efficacy and safety of WJ-MSC transplantation in T2DM. METHODS: Twenty-two patients with T2DM were enrolled and received WJ-MSC transplantation through one intravenous injection and one intrapancreatic endovascular injection (catheterization). They were followed up for 12 months after transplantation. The primary endpoints were changes in the levels of glycated hemoglobin and C-peptide and the secondary endpoints included insulin dosage, fasting blood glucose (FBG), post-meal blood glucose (PBG), inflammatory markers and T lymphocyte counts. RESULTS: WJ-MSC transplantation significantly decreased the levels of glucose and glycated hemoglobin, improved C-peptide levels and beta cell function, and reduced markers of systemic inflammation and T lymphocyte counts. No major WJ-MSC transplantation-related adverse events occurred, but data suggest a temporary decrease in levels of C-peptide and beta cell function at one month after treatment, possibly related to intrapancreatic endovascular injection. CONCLUSIONS: Our data demonstrate that treatment with WJ-MSCs can improve metabolic control and beta cell function in patients with T2DM. The therapeutic mechanism may involve improvements in systemic inflammation and/or immunological regulation. TRIAL REGISTRATION: Chinese Clinical Trial Register ChiCTR-ONC-10000985. Registered 23 September 2010.

Comparative analysis of curative effect of CT-guided stem cell transplantation and open surgical transplantation for sequelae of spinal cord injury.

BACKGROUND: This study compared the clinical efficacies, advantages and disadvantages of two transplantation approaches for treating spinal cord injury: open surgical exploration combined with local stem cell transplantation (referred to as open surgical transplantation) and local stem cell transplantation by CT-guided puncture (referred to as CT-guided transplantation). METHODS: The patients were divided into the following three groups to perform a retrospective controlled study: Group A included nine patients who underwent open surgical transplantation, Group B included nine patients who underwent CT-guided transplantation, and Group C included nine patients who did not receive stem cell transplantation. The Abbreviated Injury Scale (AIS), the American Spinal Injury Association (ASIA) score and the motor evoked potentials (MEP) examination were utilized to compare the differences in the clinical efficacies. The advantages and disadvantages of the two transplantation approaches were also compared, including the surgical risks, the possibility of repeating the operation, the interval between surgery and rehabilitation exercises and the scope of conditions suitable for the operation. RESULTS: Whether evaluated by the AIS grading scale, the ASIA score or the MEP results, there were significant differences in the clinical efficacy among the three patient groups. Group B exhibited the best clinical outcome, followed by Group A, and Group C fared the worst. The CT-guided transplantation had the advantages of lower surgical risk, the potential to repeat the operations within a short time-frame and a short interval between surgery and rehabilitation exercise compared with the open surgical transplantation. The conditions that are suitable for CT-guided transplantation versus the conditions suitable for open surgical transplantation are not identical. The application scopes for the two approaches had their respective strengths. CONCLUSIONS: CT-guided stem cell transplantation was confirmed as a safe and effective approach to treat sequelae of spinal cord injury with the advantages of simpler operation, minimal invasion, less adverse reaction and quicker recovery. CLINICAL TRIALS REGISTRATION NUMBER: ChiCTR-TNRC-12002477.

Effects of bone marrow mesenchymal stromal cells on gross motor function measure scores of children with cerebral palsy: a preliminary clinical study.

BACKGROUND AIMS: Pre-clinical evidence indicates that autologous bone marrow-derived mesenchymal stromal cell (BM-MSC) transplantation improves motor function in patients with central nervous system disorders. METHODS: After providing informed consent, 52 patients with cerebral palsy (CP) who met the study criteria received BM-MSC transplantation. Gross motor function was assessed using the Gross Motor Function Measure (GMFM)-88 and GMFM-66 scales at baseline (before transplantation) and at 1 month, 6 months and 18 months post-transplantation. The participants completed the trial without visible side effects. The GMFM-66 percentile (motor growth curves) was used as the control index of motor function to exclude the interference of improvement with age. RESULTS: The score domains A, B, C and D and the total GMFM-88 and GMFM-66 scores in participants increased at 1 month, 6 months and 18 months post-transplantation compared with the baseline value (P < 0.01). The scores of domain E also increased at 6 months and 18 months post-transplantation, although they were not significantly increased at 1 month post-transplantation. There were significant increases in the GMFM-66 score and the GMFM-66 percentile corresponding to patient age and Gross Motor Function Classification System level after cell transplantation. CONCLUSIONS: Autologous BM-MSC transplantation appears to be a feasible, safe and effective therapy for patients with CP. The treatment improved the development of children with CP with regard to motor function.