Analysis and clinical significance of peripheral blood routine changes of platelet donors with ultra-high frequency donation.

BACKGROUND: Increasing platelet donation frequency has become an important way to meet the growing clinical platelet need. Accordingly, the problem of whether the increase in platelet donation times will have an adverse effect on the health of donors has attracted more and more attention, and become an important factor affecting the donor enthusiasm and the safety of blood collection and supply. METHODS: Eleven ultra-high frequency platelet donors who donated more than or equal to 20 times in 2021 were selected, and the main peripheral blood routine indicators of hemoglobin, platelet and hematocrit were analyzed. RESULTS: The above indicators of all donors fluctuated with the increase of donation times. Among them, older donors (≥50 years old) exhibited a significant downward trend in the above three indicators, and one young donor showed a downward trend in hemoglobin and hematocrit indicators. While the other donors showed the relatively stable performance of the above indicators. CONCLUSION: The effect of ultra-high frequency platelet donation on the main peripheral blood indexes of donors shows obvious age compliance, that is, the potential harm to ultra-high frequency donors older than 50 years is significantly greater than that of donors of other ages. Older platelet donors should be cautious about ultra-high frequency donations to avoid adverse health hazards. Meanwhile, the work will provide technical reference for the more scientific and efficient development of the platelet harvesting work and the establishment of the clinical blood supply system for related patients.

Neuroprotective role of Nrf2 on hypoxic-ischemic brain injury in neonatal mice.

Inflammation and oxidative stress play a key role in mediating the pathophysiology of hypoxic-ischemic (HI) brain injury. Nrf2 is a transcriptional factor that contributes to the innate defense of the body against oxidative stress and inflammation. The current study investigated the effect of Nrf2 in neonatal HI brain injury using Nrf2-/- mice. Nrf2-/- and wild-type Nrf2+/+ mice on a C57BL/6J background at postnatal day 9 underwent unilateral common carotid artery ligation, followed by hypoxia. Brain damage was determined by infarct size measurement. Apoptosis was evaluated by measuring the expression of Bax and Bcl-2. The levels of inflammatory cytokines and mediators involved in oxidative stress were measured. Nrf2 knockout exacerbated HI injury-induced brain infarct and cell apoptosis in the brain. Nrf2-/- mice showed increased inflammatory cytokines and MDA, and reduced activities of antioxidant enzymes including CAT, GSH-Px, and SOD. Nrf2-/- mice showed reduced HO-1 expression after HI injury compared with wild-type mice. This study supported a protective effect of Nrf2 in neonatal HI brain injury.

miR-520 promotes DNA-damage-induced trophoblast cell apoptosis by targeting PARP1 in recurrent spontaneous abortion (RSA).

The establishment and maintenance of successful pregnancy mainly depends on trophoblast cells. Their dysfunction has been implicated in recurrent spontaneous abortion (RSA), a major complication of pregnancy. However, the underlying mechanisms of trophoblasts dysfunction remain unclear. DNA-damage-induced cell apoptosis has been reported to play a vital role in cell death. In this study, we identified a novel microRNA (miR-520) in RSA progression via regulating trophoblast cell apoptosis. Microarray analysis showed that miR-520 was highly expressed in villus of RSA patients. By using flow cytometry analysis, we observed miR-520 expression was correlated with human trophoblast cell apoptosis in vitro, along with decreased poly (ADP-ribose) polymerase-1 (PARP1) expression. With the analysis of clinic samples, we observed that miR-520 level was negatively correlated with PARP1 level in RSA villus. In addition, overexpression of PARP1 restored the miR-520-induced trophoblast cell apoptosis in vitro. The status of chromosome in trophoblast implied that miR-520-promoted DNA-damage-induced cell apoptosis to regulate RSA progression. These results indicated that the level of miR-520 might associate with RSA by prompting trophoblast cell apoptosis via PARP1 dependent DNA-damage pathway.

Plasma microRNA-16-5p, -17-5p and -20a-5p: Novel diagnostic biomarkers for gestational diabetes mellitus.

AIM: To explore whether plasma microRNA-16-5p, -17-5p and -20a-5p can be used as diagnostic biomarkers in gestational diabetes mellitus (GDM) and to investigate the relationship between those microRNAs and the risk factors of GDM (body mass index [BMI], insulin resistance [IR] and tumor necrosis factor-α (TNF-α)). METHODS: A total of 85 pregnant women with GDM and 72 pregnant women without GDM were enrolled in this study. The plasma concentration of microRNAs (microRNA-16-5p, -17-5p, -19a-3p, -19b-3p, -20a-5p) was measured using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Spearman's correlation analysis was used to evaluate the correlation between those microRNAs and the risk factors of GDM, and receiver operating characteristic curve analysis was used to evaluate diagnostic sensitivity and specificity. RESULTS: Compared with non-GDM women, the relative and absolute expression of plasma microRNA-16-5p, -17-5p, -20a-5p from GDM women were significantly upregulated, when those women were diagnosed as GDM. During pregnancy, the expression of those microRNAs from GDM women also were significantly upregulated. The expression of those microRNAs was also positively correlated with IR, a risk factor of GDM. Plasma microRNA-16-5p, -17-5p, -20a-5p reflected an obvious separation between GDM women and non-GDM women, with areas under the curve of 0.92 (95%CI: 0.871-0.984), 0.88 (95%CI: 0.798-0.962), and 0.74 (95%CI: 0.618-0.870), respectively, cut-offs >2554, 1820, 3886 copies/µL, respectively; sensitivity 41.6%, 21.4% and 17.8%, respectively; and specificity 95.8%, 95.4% and 95.4%, respectively. CONCLUSION: Plasma microRNA-16-5p, -17-5p and -20a-5p are potential diagnostic biomarkers in GDM.

Effect of family-centered interventions for perinatal depression: an overview of systematic reviews.

Objective: This study aimed to evaluate and conclude the quality of critically systematic reviews (SRs) of the efficacy of family-centered interventions on perinatal depression. Methods: SRs of the efficacy of family-centered interventions on perinatal depression were systematically searched in nine databases. The retrieval period was from the inception of the database to December 31, 2022. In addition, two reviewers conducted an independent evaluation of the quality of reporting, bias risk, methodologies, and evidence using ROBIS (an instrument for evaluating the bias risk of SRs), Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), AMSTAR 2 (an assessment tool for SRs), and grading of recommendations, assessment, development and evaluations (GRADE). Results: A total of eight papers satisfied the inclusion criteria. In particular, AMSTAR 2 rated five SRs as extremely low quality and three SRs as low quality. ROBIS graded four out of eight SRs as "low risk." Regarding PRISMA, four of the eight SRs were rated over 50%. Based on the GRADE tool, two out of six SRs rated maternal depressive symptoms as "moderate;" one out of five SRs rated paternal depressive symptoms as "moderate;" one out of six SRs estimated family functioning as "moderate," and the other evidence was rated as "very low" or "low." Of the eight SRs, six (75%) reported that maternal depressive symptoms were significantly reduced, and two SRs (25%) were not reported. Conclusion: Family-centered interventions may improve maternal depressive symptoms and family function, but not paternal depressive symptoms. However, the quality of methodologies, evidence, reporting, and bias of risk in the included SRs of family-centered interventions for perinatal depression was not satisfactory. The above-mentioned demerits may negatively affect SRs and then cause inconsistent outcomes. Therefore, SRs with a low risk of bias, high-quality evidence, standard reporting, and strict methodology are necessary to provide evidence of the efficacy of family-centered interventions for perinatal depression.

Treadmill training improves cognitive function by increasing IGF2 targeted downregulation of miRNA-483.

Optimal exercise can promote the development of cognitive functions. Nevertheless, mechanisms that elicit these positive effects of exercise still need to be elucidated. Insulin-like growth factor 2 (IGF2) is known to act as a potent enhancer of memory and cognitive functions, whereas the mechanism by which IGF2 regulates cognitive functions in terms of moderate treadmill exercise remains largely vague. In the study, rats were subjected to low-, moderate-, and high-intensity treadmill training for 6 weeks. Then, the Morris water maze test was used to investigate spatial learning and memory ability in rats subjected to treadmill exercises of different intensities. Subsequently, gene chip and bioinformatics analyses were used to explore IGF2 and predict target microRNAs (miRNAs). Quantitative real-time polymerase chain reaction, western blot, and immunofluorescence analysis were performed to detect the levels of IGF2. Furthermore, IGF2-small interfering RNA, the miRNA-483-mimic, and the miRNA-483-inhibitor were transfected to determine the role of IGF2 and miRNA-483 in the growth of hippocampal neurons. The results of the Morris water maze test showed that moderate-intensity treadmill training enhanced cognitive functions; meanwhile, the expression of IGF2 was significantly upregulated in the hippocampus after moderate-intensity treadmill exercise. From databases, miRNA-483 was screened and predicted as the target gene of IGF2. Moreover, silencing IGF2 inhibited neurite growth in the hippocampus of rats, the miRNA-483-inhibitor ameliorated silencing IGF2 induced impairment of hippocampal neurons. These findings suggested that treadmill training could enhance cognitive functions, wherein the underlying mechanism involved an increase in the expression of IGF2 and downregulation of miRNA-483.

Relationship between motor fitness, fundamental movement skills, and quality of movement patterns in primary school children.

Seefeldt`s classic motor development pyramid model recognizes the significance of fundamental movement skills (FMS) in physical activities and proposes a "proficiency barrier" between FMS and higher-level specific sports skills during middle childhood. However, the relationship between the layers of the conceptual model has not been empirically tested. This study investigated motor fitness (MF), FMS, and quality of movement patterns (QMP) in 7-10 years old children and evaluated the relationships among them. A total of 117 children were randomly selected to take tests of MF, the Test of Gross Motor Development-2 (TGMD-2), and the Functional Movement Screen (FMS™). MF and FMS levels were classified according to percentile ranges. Two multiple (R×C) Chi-Square tests were applied to analyze the relationships between MF, FMS, and QMP. Post-hoc testing estimated the possibility of FMS and QMP to predict MF. The results showed that boys scored significantly higher on the object-control subtest and on the TGMD-2 compared to girls (p<0.001), while girls scored significantly higher on the FMS™ (p = 0.001). FMS score and QMP level were weakly correlated with MF (FMS: χ2 = 14.605, p = 0.006, Cramer`s V = 0.25; QMP: χ2 = 13.943, p = 0.007, Cramer`s V = 0.24). Thus, 60.5% of children with "excellent" FMS and 59.6% with "high" QMP were categorized as having a "good" MF. In contrast, only 23.1% of children with "poor" FMS and 24.3% with "low" QMP were classified as having a "good" MF. Our results confirm MF, FMS, and QMP are correlated with each other, although this relationship is weak. Further, a possible motor skill proficiency barrier exists already in children 7-10 years old. The study results support the promotion of physical activity and motor skill development in primary school children.

DPHC From Alpinia officinarum Ameliorates Oxidative Stress and Insulin Resistance via Activation of Nrf2/ARE Pathway in db/db Mice and High Glucose-Treated HepG2 Cells.

(R)-5-hydroxy-1,7-diphenyl-3-heptanone (DPHC) from the natural plant Alpinia officinarum has been reported to have antioxidation and antidiabetic effects. In this study, the therapeutic effect and molecular mechanism of DPHC on type 2 diabetes mellitus (T2DM) were investigated based on the regulation of oxidative stress and insulin resistance (IR) in vivo and in vitro. In vivo, the fasting blood glucose (FBG) level of db/db mice was significantly reduced with improved glucose tolerance and insulin sensitivity after 8 weeks of treatment with DPHC. In vitro, DPHC ameliorated IR because of its increasing glucose consumption and glucose uptake of IR-HepG2 cells induced by high glucose. In addition, in vitro and in vivo experiments showed that DPHC could regulate the antioxidant enzyme levels including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), thereby reducing the occurrence of oxidative stress and improving insulin resistance. Western blotting and polymerase chain reaction results showed that DPHC could promote the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), the heme oxygenase-1 (HO-1), protein kinase B (AKT), and glucose transporter type 4 (GLUT4), and reduced the phosphorylation levels of c-Jun N-terminal kinase (JNK) and insulin receptor substrate-1 (IRS-1) on Ser307 both in vivo and in vitro. These findings verified that DPHC has the potential to relieve oxidative stress and IR to cure T2DM by activating Nrf2/ARE signaling pathway in db/db mice and IR-HepG2 cells.

Inhibition of fatty acid binding protein 4 attenuates gestational diabetes mellitus.

Accumulatig evidence demonstrated that inflammation is associated with the development of gestational diabetes mellitus (GDM). Fatty acid-binding protein 4 (FABP4) was reported to be involved in immune response. However, the effect of FABP4 in GDM remians unclear. This study focused on the effect of FABP4 in GDM. C57BL/KsJdb/+ (db/+) mice were used for GDM mouse model . BMS-309403 (BMS) was used to inhibit FABP4 levels in GDM mouse model. IL-6 and TNF-α concentrations in serum were determined via ELISA. Serum glucose and insulin concentrations were tested using commercial glucometer and mouse insulin ELISA kit, respectively. IL-6 and TNF-α mRNA and protein levels were detected using RT-PCR and western blot, respectively. FABP4 levels were upregulated in GDM group compared with control group and were positively associated with serum IL-6 and TNF-α levels. FABP4 inhibition by BMS significantly decreased body weight and serum glucose concentrations, increasd serum insulin concentration, suppressed IL-6 and TNF-α expression both in the serum and the pancreas, enhanced little size and inhibited birth weight in GDM mouse model. Inhibition of FABP4 attenuates GDM in genetic mice.

Astragaloside IV alleviates the brain damage induced by subarachnoid hemorrhage via PI3K/Akt signaling pathway.

Subarachnoid hemorrhage (SAH) caused brain damage accounts for more than 20 % death of patients with cerebrovascular diseases. We aimed to investigate the effects of Astragaloside IV (AS-IV) on SAH-induced brain damage and its underlying mechanism. SAH rat model was established and treated with or without AS-IV. Brain injury and function were evaluated by neurological score, brain water content, Nissl staining, and behavioral experiments using Morris water maze. The protein expression related to SAH caused inflammation and neuron apoptosis were assessed. As expected, after 24 h of SAH, Garcia score, beam balance score and the number of intact neurons were significantly reduced in SAH rats compared to sham rats, but AS-IV treatment dramatically elevated the two scores and the number of intact neuron number. Brain water content that increased after SAH was also declined in AS-IV treated rats compared to untreated rats. In addition, SAH rats treated with AS-IV also showed better neurological outcomes than untreated SAH rats including shorter escape time and swimming distance, longer quadrant stay in the Morris water maze and increased fall latency from the rod rotating. In addition, in the SAH rats, the anti-apoptosis pathway phosphoinositide 3-kinase (PI3K)/ protein kinase B (Akt) was activated while nuclear factor-κB (NF-κB) signaling was markedly repressed by AS-IV. Several apoptosis associated genes including FoxO1, Bim, Bax and a typical apoptosis marker cleaved-caspase-3 were all downregulated by AS-IV. In conclusion, this study found a protective role of AS-IV in SAH-induced brain injury through regulating PI3K and NF-κB signaling pathways.

Cryptotanshinone ameliorates placental oxidative stress and inflammation in mice with gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is a conditional diabetes which is defined as any degree of glucose intolerance or high blood glucose levels during any phase of pregnancy. It causes chronic severe damage to health of the pregnant women and their offspring. In this study, we aimed to study the protective effects of Cryptotanshinone on GDM-related impairments. We measured blood glucose levels, serum insulin levels, biochemical indexes, oxidative stress, inflammation and the activation of NF-κB signaling pathway in the blood and placenta of GDM mice. It is found that Cryptotanshinone significantly decreased blood glucose levels, oxidative stress, inflammation and NF-κB signaling with an increase of serum insulin levels in the placenta and blood of GDM mice. Taken together, Cryptotanshinone effectively ameliorated GDM, which suggested that Cryptotanshinone could be served as a promising therapeutic drug for GDM patients.

An investigation on the polymorphisms of two DNA repair genes and susceptibility to ESCC and GCA of high-incidence region in northern China.

AIM: To investigate the possible association of three SNPs, XRCC2 C41657T, XRCC2 G4234C and XRCC3 A17893G with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA) in a population of northern China. METHODS: XRCC2 C41657T, XRCC2 G4234C and XRCC3 A17893G SNP were genotyped by polymerase-chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis in 583 cancer patients (329 ESCC and 254 GCA) and 614 healthy controls. RESULTS: The genotype distribution of the XRCC2 C41657T in ESCC and GCA patients were significantly different from that in healthy controls (P values = 0.04 and 0.04 respectively). And a significant difference was found in the allele distribution of GCA patients from that in controls (P = 0.01). The XRCC2 C41657T polymorphism was associated with a modest enhancement in ESCC risk and GCA risk: OR for C/T genotype was 1.38 (1.01-1.89) in GCA risk and for T/T genotype was 2.24 (1.10-4.57) in ESCC risk. When stratified for age, smoking status and family history of UGIC, the C/T genotype showed a modest significant trend on the risk of GCA patients in the groups of age < or =50 years and non-smokers, the adjusted OR were 2.84 (1.21-6.66) and 1.62 (1.06-2.49). The T/T genotype significantly increased the susceptibility of GCA patients in negative family history of UGIC (3.04, 1.02-8.32) and to ESCC patients in the group of age >50 years (3.03, 1.31-6.98), Negative family of UGIC (3.03, 1.12-7.07) and smokers (2.64, 1.02-6.83). The genotype and allele distribution of XRCC2 G4234C and XRCC3 A17893G in ESCC and GCA patients were not significantly different from that in healthy controls (all P values were above 0.05). CONCLUSION: In this study, we found that the C41657T polymorphism of XRCC2 genes might modify the risk of ESCC and GCA development.

Characteristics of olfactory ensheathing cells and microarray analysis in Tupaia belangeri (Wagner, 1841).

Tree shrews are most closely related to the primates and so possess a number of advantages in experimental studies; they have been used as an animal model in bacterial and virus infection, cancer, endocrine system disease, and certain nervous system diseases. Their olfactory ensheathing cells (OECs) are able to release several cytokines to promote neuronal survival, regeneration and remyelination. The present study used western blot analysis to identify antibody specificity in protein extracts from whole tree shrew brains to identify the specificity of p75 nerve growth factor receptor (NGFR) derived from rabbits (75 kDa). OECs were cultured and isolated, then stained and identified using the antibodies for p75NGFR. To investigate the capacity of OECs to express cytokines and growth factors, microarray technology was used, and the analysis revealed that OECs were able to express 9,821 genes. Of these genes, 44 genes were from the neurotrophic factor family, which may indicate their potential in transplantation in vivo. The present study considered the function of OECs as revealed by other studies, and may contribute to future research.

[The association of XRCC2 gene polymorphism with susceptibility to esophageal squamous cell carcinoma and gastric cardiac adenocarcinoma in China].

OBJECTIVE: To investigate the possible association of single nucleotide polymorphism (SNP) at the 41657C/T position and 4234G/C position of X-ray repair cross-complementing gene 2 (XRCC2) with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA) in a population of high incidence region, Ci county and She county of Hebei. METHODS: The genotypes of XRCC2 41657C/T and 4234G/C SNPs were detected by polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP) analysis in 330 ESCC patients, 254 GCA patients and 629 healthy controls. RESULTS: The genotype frequency of XRCC2 41657C/T in ESCC patients (67.8%, 26.4% and 5.8%) was significantly different from that in controls (68.8%, 28.8% and 2.4%; chi square was 7.43, P was 0.02). Compared with CC genotype, TT genotype significantly increased the risk of developing ESCC (OR=2.12, 95%CI: 1.03-4.35). The genotype (59.9%, 35.8% and 4.3%) and allelotype distributions ofXRCC2 41657C/T in GCA patients were significantly different from that in controls (chi square was 7.46 and 7.23, P was 0.02 and 0.01). Compared with CC genotype, CT genotype significantly increased the risk of developing GCA (OR=1.38, 95%CI: 1.01-1.89). The genotype and allelotype distributions of the 4234G/C SNPs in ESCC and GCA patients were not significantly different from that in controls (all P values were above 0.05). Compared with GG genotype, the CG and CC genotype of XRCC2 4234G/C did not show significant effect on the risk of developing ESCC and GCA. When the two XRCC2 SNPs were combined analyzed, the haplotype distribution in GCA patients was significantly different from that in controls (chi square was 13.28, P was less than 0.01). Compared with 41657C/4234G haplotype, 41657C/4234C and 41657T/4234G haplotypes significantly increased the risk of developing GCA (OR were 1.44 and 1.55, 95%CI were 1.06-1.95 and 1.18-2.02, respectively). CONCLUSION: In high incidence region of Hebei province, we conclude that XRCC2 41657C/T polymorphism has a potential to be a susceptibility factor for ESCC and GCA while XRCC2 4234G/C polymorphism may not provide a useful marker to predict susceptibility to ESCC and GCA. However, the 41657C/4234C and 41657T/4234G haplotypes might increase the risk of developing GCA.

Simvastatin Alleviates Pathology in a Rat Model of Preeclampsia Involving ERK/MAPK Pathway.

Preeclampsia (PE) is a pregnancy-specific condition characterized by new-onset hypertension. There is evidence suggesting that imbalances of angiogenic factors, oxidative stress, and inflammation may be central to the pathogenesis of PE. We sought to investigate whether simvastatin would reduce mean arterial pressure, restore the angiogenic balance, and ameliorate inflammation and oxidative stress in a nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (l-NAME)-induced rat model of PE. We found that blood pressure was significantly increased in the l-NAME group compared to normal pregnant dams ( P < .01), and simvastatin reduced this difference. In addition, dams from the l-NAME group showed lower vascular endothelial growth factor (VEGF) and interleukin (IL) 10 levels and higher plasma-soluble FMS-like tyrosine kinase 1 (sFlt-1), tumor necrosis factor α (TNF-α), and oxidative stress marker malondialdehyde (MDA) levels as compared to control dams ( P < .01, for all). Interestingly, simvastatin treatment significantly increased VEGF and IL-10 levels while decreased sFlt-1, TNF-α, and MDA levels compared to the untreated l-NAME group. Moreover, simvastatin treatment significantly upregulated protein expression of placental p-extracellular signal-regulated kinase (ERK1), p-p38 mitogen-activated protein kinase (MAPK), p-c-Jun N-terminal kinase, and p-protein kinase B compared to untreated l-NAME control. These results suggest that simvastatin treatment restores angiogenic balance and ameliorates inflammation and oxidative stress in a rat model of PE involving ERK/MAPK pathway.

Crocin attenuates hemorrhagic shock-induced oxidative stress and organ injuries in rats.

We aimed to evaluate the effect of natural antioxidant crocin in alleviating hemorrhagic shock (HS)-induced organ damages. HS rats were treated with crocin during resuscitation. Mortality at 12h and 24h post resuscitation was documented. HS and resuscitation induced organ injuries, as characterized by elevated wet/dry ratio, quantitative assessment ratio, blood urea nitrogen, creatinine, aspartate aminotransferase and alanine aminotransferase, whereas rats received crocin treatment demonstrated improvements in all the above characteristics. This protective effect coincided with reduced malondialdehyde and increased glutathione in both serum and lung tissues, indicating attenuated oxidative stress in crocin-treated rats. Myeloperoxide levels in lung, kidney and liver were also reduced. Crocin can potentially be used to protect organs from HS-induced damages during resuscitation due to its anti-oxidative role.

Inhibition of Inflammatory Response by Crocin Attenuates Hemorrhagic Shock-Induced Organ Damages in Rats.

Hemorrhagic shock (HS) is associated with an excessive activation of inflammation, contributing to multiple organ failure in numerous medical or surgical conditions. To explore the therapeutic potential of crocin, a natural compound with anti-inflammatory properties, we administered crocin to rats during resuscitation following HS induced by withdrawing blood. Compared with control animals which were sham-treated, HS-operated rats showed organ damages as manifested by enhanced markers of multiple organ dysfunctions. Crocin treatment substantially reduced these parameters in rats subjected to HS, suggesting an alleviation of tissue injuries such as in the kidney, liver, pancreas, and muscle. The activation of NF-κB (nuclear factor κB) pathway in lung tissue by HS, as shown by increased nuclear translocation of p65 and IκBα phosphorylation, was diminished by crocin treatment. The crocin administration also significantly decreased the serum levels of proinflammatory cytokine TNF-α (tumor necrosis factor-α) and interleukin (IL)-6, whereas increased the level of anti-inflammatory cytokine IL-10 in HS-operated rats. These studies indicate that crocin administration may reduce inflammation-driven tissue damage in patients with HS.

Bone Marrow Mesenchymal Stem-Cell Transplantation Promotes Functional Improvement Associated with CNTF-STAT3 Activation after Hemi-Sectioned Spinal Cord Injury in Tree Shrews.

Hemi-sectioned spinal cord injury (hSCI) can lead to spastic paralysis on the injured side, as well as flaccid paralysis on the contralateral side, which can negatively affect a patient's daily life. Stem-cell therapy may offer an effective treatment option for individuals with hSCI. To examine the role of bone marrow mesenchymal stem cells (BMSCs) transplantation on hSCI and explore related mechanisms in the tree shrews, here, we created a model of hSCI by inducing injury at the tenth thoracic vertebra (T10). Hoechst 33342-labeled BMSCs derived from adult tree shrews were isolated, cultured, and implanted into the spinal cord around the injury site at 9 days after injury. The isolated BMSCs were able to survive, proliferate and release a variety of neurotrophic factors (NTFs) both in vitro and in vivo. At 28 days after injury, compared with the sham group, the hSCI group displayed scar formation and dramatic elevations in the mean interleukin 1 beta (IL-1ß) density and cell apoptosis level, whereas the expression of signal transducer and activator of transcription 3 (STAT3) and ciliary neurotrophic factor (CNTF) mRNA was reduced. Following BMSC transplantation, motoneurons extent of shrinkage were reduced and the animals' Basso, Beattie, and Bresnahan (BBB) locomotion scale scores were significantly higher at 21 and 28 days after injury when compared with the injured group. Moreover, the hSCI-induced elevations in scar formation, IL-1ß, and cell apoptosis were reduced by BMSC transplantation to levels that were close to those of the sham group. Corresponding elevations in the expression of STAT3 and CNTF mRNA were observed in the hSCI + BMSCs group, and the levels were not significantly different from those observed in the sham group. Together, our results support that grafted BMSCs can significantly improve locomotor function in tree shrews subjected to hSCI and that this improvement is associated with the upregulation of CNTF and STAT3 signaling.

Neuroprotective effect of breviscapine on traumatic brain injury in rats associated with the inhibition of GSK3ß signaling pathway.

Breviscapine, a standardized Chinese herbal medicine extracted from Erigeron breviscapine, has been widely used to treat cerebrovascular diseases. However, there are no reports about the neuroprotective effects and underlying molecular mechanisms of breviscapine on traumatic brain injury (TBI). Therefore, this study was aimed to investigate the effects of breviscapine on rats with TBI insult and illuminate the underlying mechanism. We created a traumatic brain-injured model with breviscapine lateral ventricle injection and evaluated the expressional changes of glycogen synthase kinase 3 beta (GSK3ß) as well as the GSK3ß-involved signaling pathways including apoptosis and axonal growth. At 7, 14, 21days after injection, we found a great reduction of motor disability in TBI rats following breviscapine treatment, which was accompanied with a notably increased expression of phospho-Ser9-GSK3ß (p-Ser9-GSK3ß) and decreased expression of phosphor-Try216-GSK3ß (p-Try216-GSK3ß) at 7days after injection. Concomitantly, an enhanced expression of synaptic marker synaptophysin (SYP) together with a weakened expression of pro-apoptotic caspase3 was observed after TBI rats were treated with breviscapine. Terminal deoxynucleotidyl transferase deoxy-UTP-nick end labeling (TUNEL) immunohistochemical assay and SYP immunofluorescence staining also confirmed the result. This study suggests that breviscapine inhibits the GSK3ß signaling pathway to promote neurobehavioral function following neurotrauma. These events may provide a new insight into the mechanism of breviscapine treating brain injury.