A cross-sectional survey among patients and prescribers on insulin dosing irregularities and impact of mild (self-treated) hypoglycemia episodes in Spanish patients with type 2 diabetes as compared to other European patients

Background and objectiveIn Spain, data suggest that 13.8% of adults have diabetes. Two important aspects in diabetes management are mild hypoglycemic episodes and poor treatment adherence. This study assesses the impact of missed insulin doses and prevalence of mistimed and reduced insulin doses and mild hypoglycemia in patients with type 2 diabetes treated with basal insulin analogues in Spain, and compares the data collected to pooled data from 8 other European countries (OECs).Materials and methodsGAPP2 was an international, online, cross-sectional study of diabetic patients aged ≥40 years treated with long-acting insulin analogues and their healthcare professionals. Patients and healthcare professionals were recruited from online research panels. Data reported in Spain are compared to pooled data from 8 OECs.ResultsIn Spain, 1–3% of patients reported they had reduced, missed, or mistimed at least one insulin does in the previous month. Significantly more OEC patients reported dosing irregularities (15–23%; all P < 0.01). In Spain, 77% of patients were worried and 59% felt guilty for missing a dose of basal insulin, while 24% reported that they were very worried about nocturnal hypoglycemia. Significantly fewer OEC patients reported worrying (47%; P < 0.01) and feeling guilty (37%; P < 0.01) about missing an insulin dose, or worry about nocturnal hypoglycemia (12%; P < 0.01).ConclusionsIn Spain, patients with type 2 diabetes report fewer dosing irregularities and hypoglycemic episodes as compared to patients from OECs. However, Spanish patients appear to have a reduced quality of life related to hypoglycemia as well as worry and guilt related to insulin dosing irregularities.     

Efficacy of mesenchymal stromal cells intraspinal transplantation for patients with different degrees of spinal cord injury: A systematic review and meta-analysis

Background aimsSeveral studies have reported that mesenchymal stromal cells (MSCs) may improve neurological functions in patients with spinal cord injury (SCI). In this study, we conducted a systematic review and meta-analysis to summarize the effects of MSC treatment on different degrees of severity of SCI.MethodsSystematic searching of studies reporting outcomes of MSCs on specific injury severities of patients with SCI was performed in The National Library of Medicine (MEDLINE), Embase and Cochrane for published articles up to the 6 July 2022. Two investigators independently reviewed the included studies and extracted the relevant data. The standardized mean differences of American Spinal Injury Association (ASIA) motor score, ASIA light touch scores, ASIA pinprick scores and the Barthel index between baseline and follow-ups were pooled.ResultsA total of eight studies were included. A large majority focused on patients with ASIA grade A classification. The pooled mean differences of ASIA motor scores, ASIA light touch scores, ASIA pinprick scores and the Barthel index were –2.78 (95% confidence interval [CI] –5.12 to –0.43, P = 0.02), –18.26 (95% CI –26.09 to –10.43, P < 0.01), –17.08 (95% CI –24.10 to –10.07, P < 0.01) and –4.37 (95% CI –10.96 to 2.22, P = 0.19), respectively.ConclusionsMSC transplantation was a significantly effective therapy for patients with SCI with ASIA grade A. In the future, further studies are warranted to confirm the potential beneficial effects of MSC therapy.     

Improved motor function in dko mice by intravenous transplantation of bone marrow-derived mesenchymal stromal cells

Background aimsWe explored the potential therapeutic value of transplanting bone marrow (BM)-derived mesenchymal stromal cells (MSC) into utrophin/dystrophin-deficient double knock-out (dko) mice, a murine model of Duchenne muscular dystrophyMethodsMSC from male rats were isolated and transplanted into female dko mice via the caudal vein. Behavior and locomotor function were later evaluated, along with the expression of dystrophin and utrophin in the sarcolemma of myofiber tissues. The presence of grafted cells was confirmed via polymerase chain reaction for the sex-determining region of the Y-chromosomeResultsLocomotor activity improved significantly (P < 0.05) from 5 to 15 weeks after cell transplantation, as measured by traction, rotating rod and running wheel tests. We also found that the expression of dystrophin and utrophin increased significantly (P < 0.05) and progressively in the sarcolemma from 5 to 15 weeks after transplantation. The median lifespan of mice in the normal group (74.1 weeks) was significantly (P < 0.001) higher than those in the control (22.0 weeks) and transplantation (35.0 weeks) groups, and the median lifespan of mice in the transplantation group was significantly (P < 0.001) higher than that in the control groupConclusionsResults of this study demonstrate that BM MSC have potential value in xenogeneic transplantation therapy for muscular dystrophy.     

Transplantation of activated olfactory ensheathing cells by curcumin strengthens regeneration and recovery of function after spinal cord injury in rats

Background aimsThe pro-regeneration capabilities of olfactory ensheathing cells (OECs) remain controversial. However, little is known regarding whether the transplantation of activated OECs by curcumin (CCM) elicits neural regeneration and functional recovery after spinal cord injury (SCI) in rats, and the possible molecular mechanisms have never been investigated.MethodsPrimary OECs were treated with 1μM CCM for 1–3 days. Concomitantly, activated OECs were transplanted into the traumatic spinal cord of Sprague Dawley rats. One to 9 weeks after surgery, the assessment of behavior recovery was made using the Basso, Beattie and Bresnahan (BBB) locomotor scale; electrophysiology tests, such as somatosensory evoked potential (SEP) and motor evoked potential (MEP); and the cylinder test. Pathological study, including hematoxylin and eosin staining and immunofluorescence staining for neurofilaments (NFs), was conducted at 5 weeks post-surgery. In addition, activation profiles of OECs by CCM stimulus were assessed and levels of transglutaminase-2 (TG2) and phosphatidylserine receptor (PSR) in OECs stimulated by CCM were further determined.ResultsCCM remarkably enhanced OEC proliferation, improved cell viability and strengthened secretion of neurotrophins and anti-inflammatory factors. In addition, the levels of TG2 and PSR in CCM-treated OECs were significantly elevated. More importantly, beyond 1 week post-transplantation of CCM-treated OECs into lesioned spinal cord, BBB score and cylinder test score were significantly higher than that seen in the other three groups and a more postponed latent SEP and MEP period was noted. Furthermore, 5 weeks later, numerous, well-arranged NF-positive nerve fibers, lesions with less cavities and reduced levels of pro-inflammatory cytokines were found in activated OEC implantation groups. In addition, the number of NF-positive fibers was significantly improved and the number and area of both cavities and gliotic scars were remarkably decreased compared with the corresponding controls.ConclusionsTransplantation of OECs activated by CCM promotes neural regeneration and functional recovery following SCI, the underlying mechanisms of which are intimately associated with the elevated production of neurotrophic factors and anti-inflammatory factors in OECs stimulated by CCM as well as reduced pro-inflammatory cytokines from the post-contusion spinal cord. In addition, OECs activated by CCM were mediated through TG2 and PSR.     

The Effects of Co-transplantation of Olfactory Ensheathing Cells and Schwann Cells on Local Inflammation Environment in the Contused Spinal Cord of Rats

Inflammatory response following spinal cord injury (SCI) is important in regulation of the repair process. Olfactory ensheathing cells (OECs) and Schwann cells (SCs) are important donor cells for repairing SCI in different animal models. However, synergistic or complementary effects of co-transplantation of both cells for this purpose have not been extensively investigated. In the present study, we investigated the effects of co-transplantation of OECs and SCs on expression of pro- or anti-inflammatory factor and polarization of macrophages in the injured spinal cord of rats. Mixed cell suspensions containing OECs and SCs were transplanted into the injured site at 7 days after contusion at the vertebral T10 level. Compared with the DMEM, SC, or OEC group, the co-transplantation group had a more extensive distribution of the grafted cells and significantly reduced number of astrocytes, microglia/macrophage infiltration, and expression of chemokines (CCL2 and CCL3) at the injured site. The co-transplantation group also significantly increased arginase⁺/CD206⁺ macrophages (IL-4) and decreased iNOS⁺/CD16/32⁺ macrophages (IFN-γ), which was followed by higher IL-10 and IL-13 and lower IL-6 and TNF-α in their expression levels, a smaller cystic cavity area, and improved motor functions. These results indicate that OEC and SC co-transplantation could promote the shift of the macrophage phenotype from M(IFN-γ) to M(IL-4), reduce inflammatory cell infiltration in the injured site, and regulate inflammatory factors and chemokine expression, which provide a better immune environment for SCI repair.     

Modulation of the vascular response to injury by autologous blood-derived outgrowth endothelial cells

Delivery of a heterogeneous population of cells with endothelial phenotype derived from peripheral blood has been shown to improve vascular responses after balloon arterial injury in an endothelium-dependent manner. Refinement of culture techniques has enabled the generation of outgrowth endothelial cells (OECs), a homogeneous population of distinctly endothelial cells expanded from circulating progenitor cells. The present study tested the hypothesis that OEC delivery would confer vascular protection after balloon arterial injury in a rabbit model. Rabbit peripheral blood mononuclear cells (PBMCs) were cultured in endothelial growth medium for 4-5 wk, yielding proliferative OECs with distinct endothelial phenotype (morphology, incorporation of acetylated LDL, and expression of endothelial nitric oxide synthase and caveolin-1 but not CD14). Animals underwent balloon carotid injury immediately followed by local delivery of autologous OECs for 20 min. Fluorescent-labeled OECs were detected in all layers at 4 wk, with immunostaining revealing maintenance of endothelial phenotype (von Willebrand factor-positive and RAM-11-negative) by luminal and nonluminal cells. To evaluate functional effects, additional animals received autologous OECs, saline, or freshly harvested PBMCs as noncultured cell controls by local dwell after balloon injury. Local OEC delivery improved endothelium-dependent vasoreactivity (P < 0.05 vs. saline and PBMC) and similarly reduced neointimal formation (P < 0.05 vs. saline and PBMC). These data suggest that OECs can be detected in injured arterial segments at 4 wk. Moreover, delivery of OECs confers greater vascular protection than PBMCs or saline controls and may thus offer a novel, autologous strategy to limit the response to mechanical injury.     

Current evidence on mesenchymal stem cell therapy for traumatic spinal cord injury: systematic review and meta-analysis

Background aimsThe authors aim to analyze the evidence in the literature regarding the efficacy and safety of mesenchymal stem cell (MSC) therapy in human subjects with traumatic spinal cord injury (SCI) and identify its potential role in the management of SCI.MethodsThe authors conducted independent and duplicate searches of electronic databases, including PubMed, Embase and the Cochrane Library, until May 2020 for studies analyzing the efficacy and safety of stem cell therapy for SCI. American Spine Injury Association (ASIA) impairment scale (AIS) grade improvement, ASIA sensorimotor score, activities of daily living score, residual urine volume, bladder function improvement, somatosensory evoked potential (SSEP) improvement and adverse reactions were the outcomes analyzed. Analysis was performed in R platform using OpenMeta[Analyst] software.ResultsNineteen studies involving 670 patients were included for analysis. On analysis, the intervention group showed statistically significant improvement in AIS grade (P < 0.001), ASIA sensory score (P < 0.017), light touch (P < 0.001), pinprick (P = 0.046), bladder function (P = 0.012), residual urine volume (P = 0.023) and SSEP (P = 0.002). However, no significant difference was noted in motor score (P = 0.193) or activities of daily living score (P = 0.161). Although the intervention group had a significant increase in complications (P < 0.001), no serious or permanent adverse events were reported. On subgroup analysis, low concentration of MSCs (<5 × 10⁷ cells) and initial AIS grade A presentation showed significantly better outcomes than their counterparts.ConclusionsThe authors’ analysis establishes the efficacy and safety of MSC transplantation in terms of improvement in AIS grade, ASIA sensory score, bladder function and electrophysiological parameters like SSEP compared with controls, without major adverse events. However, further research is needed to standardize dose, timing, route and source of MSCs used for transplantation.     

Cathepsin B inactivation attenuates the apoptotic injury induced by ischemia/reperfusion of mouse liver

Background: A major mechanism underlying warm ischemia/reperfusion (I/R) injury during liver transplantation is the activation of the caspase chain, which leads to apoptosis. Recently, it was demonstrated that the release of cathepsin B, a cysteine protease, from the cytosol in liver injury induces mitochondrial release of cytochrome c and the activation of caspase-3 and -9, thereby leading to apoptosis. The aim of this study was to ascertain if cathepsin B inactivation attenuates the apoptotic injury due to I/R in mouse liver. Methods: A model of segmental (70%) hepatic ischemia was used. Eighteen mice were anesthetized and randomly divided into three groups: (1) Control group: sham operation (laparotomy); (2) Ischemic group: midline laparotomy followed by occlusion of all structures in the portal triad to the left and median lobes for 60 min (ischemic period); (3) Study group: like group 2, but with intraperitoneal administration of a pharmacological inhibitor of cathepsin B (4 mg/100 g) 30 min before induction of ischemia. Serum liver enzyme levels were measured by biochemical analysis, and intrahepatic caspase-3 activity was measured by fluorometric assay; apoptotic cells were identified by morphological criteria, the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) fluorometric assay, and immunohistochemistry for caspase-3. Results: Showed that at 6 h of reperfusion, there was a statistically significant reduction in liver enzyme levels in the animals pretreated with cathepsin B inhibitor (p < 0.05). On fluorometric assay, caspase-3 activity was significantly decreased in group 3 compared to group 2 (p < 0.0001). The reduction in postischemic apoptotic hepatic injury in the cathepsin B inhibitor -treated group was confirmed morphologically, by the significantly fewer apoptotic hepatocyte cells detected (p < 0.05); immunohistochemically, by the significantly weaker activation of caspase-3 compared to the ischemic group (p < 0.05); and by the TUNEL assay (p < 0.05). Conclusion: The administration of cathepsin B inhibitor before induction of ischemia can attenuate postischemic hepatocyte apoptosis and thereby minimize liver damage. Apoptotic hepatic injury seems to be mediated through caspase-3 activity. These findings have important implications for the potential use of cathepsin B inhibitors in I/R injury during liver transplantation.     

Effects of mouse nerve growth factor in treating cerebral injury in acute period caused by cerebral hemorrhage

ObjectiveTo explore the clinical effects of mouse Nerve Growth Factor (NGF) in treating cerebral injury in acute period caused by cerebral hemorrhage, observe its influences on Natriuretic Peptide (BNP) and NF-kB Level and evaluate its safety and efficiency.Methods96 cases with acute cerebral hemorrhage from January 2016 to January 2017 in our hospital were recruited as this study, they were randomly divided into the control group and the observation group, each 48 cases. The observation group were given NGF on the treatment of the control group. NIHSS, BI score, adverse reactions records were compared in two groups before and after treatment. The clinical effective rate were evaluated. Then BNP and NF-KB Level of patients in two groups before and after treatment were detected by using ELISA.ResultsThere were no significant differences in two groups before treatment with respect to NIHSS and BI score (P > 0.05). After treatment, NIHSS score in the observation group significantly lower than the control group. BI score in the observation group significantly higher than the control group, differences had obvious significance (P < 0.05). The total effective rate in the observation group was 93.75%. The control group was 70.83%. Clinical effective rate of patients in the observation group significantly better than the control group (P < 0.05). There were no significant differences of patients in two groups before treatment with respect to BNP and NF-kB Level (P > 0.05). BNP and NF-kB Level decreased with different levels in two groups after treatment, and the observation group lower than the control group at the same time (P < 0.05).ConclusionNGF is benefit for relieving neurological function injury of patients with acute cerebral hemorrhage in acute period, improving living ability of patients. Patients have good tolerance and no adverse reactions. NGF can lower BNP and NF-kB Level. It has a certain function of inhibiting inflammatory injury caused by cerebral hemorrhage, thus protecting neuron. It is worthy of clinical promotion.     

Upregulation of NKG2D ligands in acute lymphoblastic leukemia and non-Hodgkin lymphoma cells by romidepsin and enhanced in vitro and in vivo natural killer cell cytotoxicity

Background aimsThere is a critical need to prevent and/or treat hematological relapse after allogeneic hematopoietic stem cell transplantation. The activating NKG2D receptor expressed on natural killer (NK) cells, when engaged by its corresponding ligands (MIC A/B), activates NK cells to become cytotoxic against malignant cells.MethodsWe incubated acute lymphoblastic leukemia and non-Hodgkin lymphoma cells for 24 h with 10 ng/mL of romidepsin. Flow cytometry was performed to demonstrate changes in surface expression of NKG2D ligands MIC A/B. In vitro and in vivo cytotoxicity was measured by means of modified Europium assay, and non-obese diabetic/severe combined immunodeficiency mice were xenografted with RS 4:11 cells.ResultsWe demonstrated an approximately 50, 200, 1300 and 180-fold increase in the number of cells positive for the surface expression of MIC A/B in RS 4:11 (P < 0.001), REH (P < 0.001), Ramos (P < 0.001) and Jurkat cells (P < 0.001), respectively. We further demonstrated a significant increase in NK cell–mediated in vitro cytotoxicity against RS 4:11 (P < 0.004), Ramos (P < 0.05), Jurkat (P < 0.001) and REH cells (P < 0.01), respectively. Romidepsin-mediated NK cytotoxicity was blocked by pre-incubating NK cells with anti-NKG2D-Fc in RS 4:11 (P < 0.03) and Ramos cells (P < 0.01), respectively. Finally, non-obese diabetic/severe combined immunodeficiency mice xenografted with RS 4:11 cells had a significant increase in survival (P < 0.02) in mice treated with romidepsin and interleukin-2–activated NK cells compared with each of these other treatment groups.ConclusionsRomidepsin significantly enhanced in vitro and in vivo NK cell cytotoxicity mediated in part by increased MIC A/B expression on malignant cells. This translational approach of the use of romidepsin and interleukin-2–activated NK cells should be considered in patients with relapsed/refractory leukemia or lymphoma.     

Effects of l-glutamine supplementation alone or with antioxidants on hydrogen peroxide-induced injury in human intestinal epithelial cells

Background and aimsIn situations of oxidative stress, l-glutamine (Gln) exhibits protective effects which may be potentiated by its combination with antioxidants. The aim of this study was to compare the effects of a Gln-antioxidants formula vs Gln alone in intestinal epithelial cell lines Caco-2 and HCT-8 submitted to hydrogen peroxide-induced oxidative injury.MethodsCells were cultured during 24 h with 0, 1, 2, 4, 8 or 16 mM Gln or isomolar Gln combined to cysteine, vitamine C, vitamine E, β-carotene, Zn and Se (Gln-AOX). After 24 h, membrane integrity was assessed by means of LDH leakage, the level of oxidative stress by analysis of 8-isoprostane concentration and cell viability by colorimetric-MTT assay.ResultsLDH activity decreased (P < 0,05) with a dose-dependent manner in both cell types with Gln-AOX whereas Gln decreased LDH release only in the Caco-2 line at 1 mM. For both cell lines, release of 8-isoprostane was not blunted by any treatment and increased paradoxically with 16 mM Gln (P < 0.05). Cell viability was higher (P < 0.05) using Gln-AOX vs Gln at 4, 8 and 16 mM in both cell lines.ConclusionsThese results suggest that Gln-AOX is more efficient than Gln alone to preserve cell membrane integrity and viability in intestinal cell lines submitted to oxidative injury.     

Effects of PEGylated porcine glucagon-like peptide-2 therapy in weaning piglets challenged with lipopolysaccharide

This study aims to evaluate the therapeutic effect of polyethylene glycosylated porcine glucagon-like peptide-2 (pGLP-2), a long-acting form of pGLP-2, in lipopolysaccharide (LPS)-challenged piglets. Eighteen 21-day-old weaning piglets were randomly assigned into three groups: control (saline solution), LPS (100 μg/kg LPS), and PEG–pGLP-2 (10 nmol/kg PEG–pGLP-2 + 100 μg/kg LPS). All treatments were administered intraperitoneally. Compared with the control treatment, LPS treatment significantly decreased (P < 0.05) the villus heights of the duodenum and jejunum, as well as the villus height/crypt depth ratio of the jejunum. However, PEG–pGLP-2 therapy reduced these effects (P > 0.05). Specifically, PEG–pGLP-2 infusion significantly increased the villus height/crypt depth ratio of the duodenum (P < 0.05) compared with LPS treatment. Compared with the control treatment, LPS treatment significantly increased (P < 0.05) the mRNA expression levels of interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) in the jejunum. However, PEG–pGLP-2 therapy reduced these effects (P < 0.05). Specifically, PEG–pGLP-2 infusion significantly decreased (P < 0.05) the mRNA expression levels of interleukin (IL)-8 and TNF-α in the duodenum and jejunum, IL-10 in the duodenum, and IFN-γ in the jejunum compared with the LPS treatment. LPS treatment increased the caspase-3 activity of the ileum mucosal (P < 0.05), and this effect was significantly reduced by PEG–pGLP-2 treatment. These results indicate that PEG–pGLP-2 infusion alleviates the severity of intestinal injury in weaning piglets by reducing the secretion of inflammatory cytokines and the caspase-3 activity, and increasing the villus height/crypt depth ratio.     

Olfactory Ensheathing Cells Express α7 Integrin to Mediate Their Migration on Laminin

The unique glia located in the olfactory system, called olfactory ensheathing cells (OECs), are implicated as an attractive choice for transplantation therapy following spinal cord injury because of their pro-regenerative characteristics. Adult OECs are thought to improve functional recovery and regeneration after injury by secreting neurotrophic factors and making cell-to-cell contacts with regenerating processes, but the mechanisms are not well understood. We show first that α7 integrin, a laminin receptor, is highly expressed at the protein level by OECs throughout the olfactory system, i.e., in the olfactory mucosa, olfactory nerve, and olfactory nerve layer of the olfactory bulb. Then we asked if OECs use the α7 integrin receptor directly to promote neurite outgrowth on permissive and neutral substrates, in vitro. We co-cultured α7^+/+ and α7^lacZ/lacZ postnatal cerebral cortical neurons with α7^+/+ or α7^lacZ/lacZ OECs and found that genotype did not effect the ability of OECs to enhance neurite outgrowth by direct contact. Loss of α7 integrin did however significantly decrease the motility of adult OECs in transwell experiments. Twice as many α7^+/+ OECs migrated through laminin-coated transwells compared to α7^+/+ OECs on poly-L-lysine (PLL). This is in contrast to α7^lacZ/lacZ OECs, which showed no migratory preference for laminin substrate over PLL. These results demonstrate that OECs express α7 integrin, and that laminin and its α7 integrin receptor contribute to adult OEC migration in vitro and perhaps also in vivo.     

Benefits of plerixafor for mobilization of peripheral blood stem cells prior to autologous transplantation: a dual-center retrospective cohort study

Background aimsBefore autologous stem cell transplantation (ASCT), hematopoietic stem cells must be stimulated to move from the bone marrow to the peripheral blood for harvesting. Plerixafor, a C-X-C chemokine receptor type 4 antagonist, is used to increase stem cell harvests. However, the effects of plerixafor on post-ASCT outcomes remain unclear.MethodsIn a dual-center retrospective cohort study of 43 Japanese patients who received ASCT, the authors compared transplantation outcomes in patients who underwent stem cell mobilization with granulocyte colony-stimulating factor with (n = 25) or without (n = 18) plerixafor.ResultsThe number of days to neutrophil and platelet engraftment was significantly shorter with plerixafor than without plerixafor, as assessed by univariate (neutrophil, P = 0.004, platelet, P = 0.002), subgroup, propensity score matching and inverse probability weighting analyses. Although the cumulative incidence of fever was comparable with or without plerixafor (P = 0.31), that of sepsis was significantly lower with plerixafor than without (P < 0.01). Thus, the present data indicate that plerixafor leads to earlier neutrophil and platelet engraftment and a reduction of infectious risk.ConclusionsThe authors conclude that plerixafor may be safe to use and that it reduces the risk of infection in patients with a low CD34+ cell count the day before apheresis.     

Enhancing amplification of late‐outgrowth endothelial cells by bilobalide

Transfusion of autologous late‐outgrowth endothelial cells (OECs) is a promising treatment for restenosis after revascularization. Preparing cells by in vitro amplification is a key step to implement the therapy. This study aimed to demonstrate that bilobalide, a terpenoid, enhances the OEC amplification. Human‐, rabbit‐ and rat OECs and a mouse femoral artery injury model were used. Expanding OECs used endothelial growth medium‐2 as the standard culture medium while exploring the mechanisms used endothelial basal medium‐2. Proliferation assay used MTT method and BrdU method. Migration assay used the modified Boyden chamber. Intracellular nitric oxide, superoxide anion, hydroxyl radical/peroxynitrite and H₂O₂ were quantified with DAF‐FM DA, dihydroethidium, hydroxyphenyl fluorescein and a H₂O₂ assay kit, respectively. Activated ERK1/2 and eNOS were tested with the Western blot. Bilobalide concentration‐dependently enhanced OEC number increase in vitro. Transfusion of bilobalide‐based human OECs into femoral injured athymia nude mouse reduced the intimal hyperplasia. Bilobalide promoted OEC proliferation and migration and increased the intracellular nitric oxide level. L‐NAME, a NOS inhibitor, inhibits but not abolishes OEC proliferation, migration and ERK1/2 activation. Bilobalide concentration‐dependently enhanced the eNOS Ser‐1177 phosphorylation and Thr‐495 dephosphorylation in activated OECs. Bilobalide alleviates the increase in hydroxyl radical/peroxynitrite, superoxide anion and H₂O₂ in proliferating OECs. In conclusion, nitric oxide plays a partial role in OEC proliferation and migration; bilobalide increases OEC nitric oxide production and decreases nitric oxide depletion, promoting the OEC number increase; Bilobalide‐based OECs are active in vivo. The findings may simplify the preparation of OECs, facilitating the implementation of the autologous‐OECs‐transfusion therapy.     

Protective effects of sulforaphane and aerobic exercise on acute alcoholic hepatic injury in mice

ObjectiveThe paper intends to study the protective effects of sulforaphane (SF) on acute alcoholic hepatic injury in mice by intragastric administration of SF, aerobic exercise and the approach of SF integrated with aerobic exercise.Methodology60 NIH mice were randomly divided into 6 groups of equal number according to their body weight and were intragastrically administrated with 50% ethanol. The serum and liver indexes of each group of mice were detected, and the liver was stained with oil red O for pathological examination.ResultsCompared with the model group, the serum TG and the ratio of liver to body weight of the model mice that suffered from acute alcoholic hepatic injury could be significantly decreased in the group that practiced aerobic exercise, the group administered with SF, and the group treated with the approach of SF integrated with aerobic exercise (P < 0.05). The contents of TG and MDA in liver could be significantly decreased (P < 0.05) and SOD activity could be significantly increased (P < 0.05) both in the group administered with SF and the group treated with the approach of SF integrated with aerobic exercise. Serum VLDL (P < 0.05) could also be significantly reduced in the group treated with the approach of SF integrated with aerobic exercise.ConclusionBoth SF and aerobic exercise could alleviate alcohol-induced acute alcoholic hepatic injury in mice possibly thanks to the working mechanism related to antioxidant stress that reduced the harm posed by alcohol on hepatic cells. In addition, the protective effect of SF on acute alcoholic hepatic injury in mice was stronger than that of aerobic exercise, while the approach of SF integrated with aerobic exercise had the strongest protective effect on acute alcoholic hepatic injury in mice.     

Effects of stem cells on non-ischemic cardiomyopathy: a systematic review and meta-analysis of randomized controlled trials

Background aimsTo assess the impacts of stem cell therapy on clinical outcomes in patients with non-ischemic cardiomyopathy (NICM). The effect of stem cell therapy on prognosis is unclear and controversial.MethodsThe authors performed a systematic review and meta-analysis of the effects of autologous stem cell transplantation in patients with NICM on a composite outcome of all-cause mortality and heart transplantation, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), New York Heart Association (NYHA) classification, 6-minute walk test (6-MWT) distance and serum brain natriuretic peptide (BNP) level, considering studies published before March 19, 2020.ResultsTwelve trials with 623 subjects met inclusion criteria. Compared with the control group, stem cell therapy improved LVEF (weighted mean difference [WMD], 4.08%, 95% confidence interval [CI], 1.93–6.23, P = 0.0002) and 6-MWT distance (WMD, 101.49 m, 95% CI, 45.62–157.35, P = 0.0004) and reduced BNP level (–294.94 pg/mL, 95% CI, –383.97 to –205.90, P < 0.00001) and NYHA classification (–0.70, 95% CI, –0.98 to –0.43, P < 0.00001). However, LVEDD showed no significant difference between the two groups (WMD, –0.09 cm, 95% CI, –0.23 to 0.06, P = 0.25). In 10 studies (535 subjects) employing the intracoronary route for cell delivery, mortality and heart transplantation were decreased (risk ratio [RR], 0.73, 95% CI, 0.52–1.00, P = 0.05). Furthermore, in four studies (248 subjects) with peripheral CD34+ cells, either all-cause mortality (RR, 0.44, 95% CI, 0.23–0.86, P = 0.02) or mortality and heart transplantation (RR, 0.45, 95% CI, 0.27–0.77, P = 0.003) improved in the treatment group compared with the control. The trial sequential analysis suggested the information size of LVEF, 6-WMT and BNP has been adequate for evidencing the benefits of stem cells on NICM. However, to determine the potential survival benefit, more clinical data are required to make the statistical significance in meta-analysis more conclusive.ConclusionsThis meta-analysis demonstrates that stem cell therapy may improve survival, exercise capacity and cardiac ejection fraction in NICM, which suggests that stem cells are a promising option for NICM treatment.     

Acupuncture protects from 6-OHDA-induced neuronal damage by balancing the ratio of DMT1/Fpn1

ObjectiveAcupuncture is a commonly used method to provide motor-symptomatic relief for patients with Parkinson s disease (PD). Our objective was to evaluate protective effects of acupuncture treatment and potential underlying mechanisms according to the “gut-brain axis” theory.MethodsWe employed a 6-OHDA-induced PD rat model. The effects of acupuncture on disease development were assessed by behavioural tests and immunohistochistry (IHC). ELISA, qPCR and western blot (WB) were employed to measure inflammatory parameters and Fe metabolism in the substantia nigra (SN), striatum, duodenum and blood, respectively.ResultsOur data show that acupuncture can significantly increase the expression of tyrosine hydroxylase (TH), compared with untreated and madopa treated rats (P < 0.01 and P < 0.05, respectively). Furthermore we could observe significantly decreased levels of pro-inflammatory markers in the duodenum and serum (P < 0.05), reduced deposition of Fe in the substantia nigra (P < 0.05) and but no change in transferrin expression after acupuncture treatment. The mRNA ratio of DMT1/Fpn1 in the SN of acupuncture treated rats (1.1) was comparable to that of the sham group (1.0) which differed both significantly from the untreated and madopa treated groups (P < 0.05). Furthermore, after acupuncture expression of α-synuclein was decreased in the duodenum.ConclusionsAcupuncture can reduce iron accumulation in the SN and protect the loss of dopamine neurons by promoting balanced expression of the iron importer DMT1 and the iron exporter Fpn1. Furthermore CNS iron homeostasis may be affected by reduced systemic and intestinal inflammation.     

Does Hypothermic Treatment Provide an Advantage After Spinal Cord Injury Until Surgery? An Experimental Study

We compared the effects of early and late stage hypothermia treatment after spinal cord injury. Five groups each consisting of seven rats were included in this study. In Group 1a (Clip applied-non-treatment group) and Group 1b (Clip applied-treated group) the spinal cords were harvested 1 h after the injury. In Group 2a (clip applied, non-treated group) and Group 2b (clip applied-treated group) the injured segments were harvested 24 h after injury. Group 3 was designed as the sham-operated group. The significantly lower levels of TBARS and GSH-Px in Group 2a, as compared with Group 1b suggests that the hypothermia was effective in the early stage of treatment (P < 0.05). In contrast, TBARS and GSH-Px levels were significantly increased at the 24 h timepoint following treatment (P < 0.05).Short-term systemic hypothermia reduces lipid peroxidation in the early stages after spinal cord injury. This beneficial effect disappears 24 h following systemic hypothermic treatment.