Therapeutic role of neural stem cells in neurological diseases.

The failure of endogenous repair is the main feature of neurological diseases that cannot recover the damaged tissue and the resulting dysfunction. Currently, the range of treatment options for neurological diseases is limited, and the approved drugs are used to treat neurological diseases, but the therapeutic effect is still not ideal. In recent years, different studies have revealed that neural stem cells (NSCs) have made exciting achievements in the treatment of neurological diseases. NSCs have the potential of self-renewal and differentiation, which shows great foreground as the replacement therapy of endogenous cells in neurological diseases, which broadens a new way of cell therapy. The biological functions of NSCs in the repair of nerve injury include neuroprotection, promoting axonal regeneration and remyelination, secretion of neurotrophic factors, immune regulation, and improve the inflammatory microenvironment of nerve injury. All these reveal that NSCs play an important role in improving the progression of neurological diseases. Therefore, it is of great significance to better understand the functional role of NSCs in the treatment of neurological diseases. In view of this, we comprehensively discussed the application and value of NSCs in neurological diseases as well as the existing problems and challenges.

Preparation and characterization of starch/PBAT film containing hydroxypropyl-ß-cyclodextrin/ethyl lauroyl arginate/cinnamon essential oil microcapsules and its application in the preservation of strawberry.

Cinnamon essential oil (CEO) was emulsified by hydroxypropyl-ß-cyclodextrin/ ethyl lauroyl arginate (HPCD/LAE) complex to make nanoemulsions, which were then incorporated into maltodextrin (MD) to prepare HPCD/LAE/CEO/MD microcapsules by spray drying. The starch/polybutylene adipate terephthalate (starch/PBAT, SP) based extrusion-blowing films containing above microcapsules were developed and used as packaging materials for strawberry preservation. The morphology, encapsulation efficiency, thermal and antibacterial properties of microcapsules with different formulations were investigated. The effects of microcapsules on the physicochemical and antimicrobial properties of SP films were evaluated. When the formula was 4 % HPCD/LAE-3% CEO-10% MD (HL-3C-MD), the microcapsule had the smallest particle size (3.3 µm), the highest encapsulation efficiency (84.51 %) of CEO and the best antibacterial effect. The mechanical and antimicrobial properties of the SP film were enhanced while the water vapor transmittance and oxygen permeability decreased with the incorporation of HL-3C-MD microcapsules. The films effectively reduced the weight loss rate (49.03 %), decay rate (40.59 %) and the total number of colonies (2.474 log CFU/g) and molds (2.936 log CFU/g), thus extending the shelf life of strawberries. This study revealed that the developed SP films containing HPCD/LAE/CEO microcapsules had potential applications in degradable bioactive food packaging materials.

Associations between blood inflammatory markers and bone mineral density and strength in the femoral neck: findings from the MIDUS II study.

Chronic and systematic inflammation have been related to increased risks of osteopenia and related fracture. However, studies concerning the association between low-grade inflammation and the bone mineral density (BMD) and strength of the femoral neck are still few and inconsistent. This study aimed to examine the relationships between blood inflammatory biomarkers and BMD and femoral neck strength in an adult-based cohort. We retrospectively analyzed a total of 767 participants included in the Midlife in the United States (MIDUS) study. The blood levels of inflammatory markers, including interleukin-6 (IL6), soluble IL-6 receptor, IL-8, IL-10, TNF-α and C-reactive protein (CRP), in these participants were measured, and their associations with the BMD and strength of the femoral neck were determined. We analyzed these 767 subjects with data concerning the BMD, bending strength index (BSI), compressive strength index (CSI), and impact strength index (ISI) in the femoral neck and inflammatory biomarkers. Importantly, our results suggest that strongly negative associations exist between the blood soluble IL6 receptor levels and the BMD (per SD change, Sß = -0.15; P < 0.001), CSI (per SD change, Sß = -0.07; P = 0.039), BSI (per SD change, Sß = -0.07; P = 0.026), and ISI (per SD change, Sß = -0.12; P < 0.001) in the femoral neck after adjusting for age, gender, smoked cigarettes regularly, number of years drinking, BMI and regular exercise. However, the inflammatory biomarkers, including blood IL-6 (per SD change, Sß = 0.00; P = 0.893), IL-8 (per SD change, Sß = -0.00; P = 0.950), IL-10 (per SD change, Sß = -0.01; P = 0.854), TNF-α (per SD change, Sß = 0.04; P = 0.260) and CRP (per SD change, Sß = 0.05; P = 0.137), were not strongly associated with the BMD in the femoral neck under the same conditions. Similarly, there was no significant difference in the relationships between the inflammatory biomarkers (IL-6, IL-8, IL-10, TNF-α and CRP) and the CSI, BSI, and ISI in the femoral neck. Interestingly, in concomitant inflammation-related chronic diseases, only arthritis affected the soluble IL-6 receptor and the CIS (interaction P = 0.030) and SIS (interaction P = 0.050) in the femoral neck. In this cross-sectional analysis, we only observed that high blood levels of soluble IL-6 receptor were strongly associated with reduced BMD and bone strength in the femoral neck. The independent associations between the other inflammatory indicators, including IL-6, IL-8, IL-10, TNF-α and CRP, and the BMD and femoral neck strength in an adult-based cohort were not significant.

P2Y12 receptor involved in the development of chronic nociceptive pain as a sensory information mediator.

Direct or indirect damage to the nervous system (such as inflammation or tumor invasion) can lead to dysfunction and pain. The generation of pain is mainly reflected in the activation of glial cells and the abnormal discharge of sensory neurons, which transmit stronger sensory information to the center. P2Y12 receptor plays important roles in physiological and pathophysiological processes including inflammation and pain. P2Y12 receptor involved in the occurrence of pain as a sensory information mediator, which enhances the activation of microglia and the synaptic plasticity of primary sensory neurons, and reaches the higher center through the ascending conduction pathway (mainly spinothalamic tract) to produce pain. While the application of P2Y12 receptor antagonists (PBS-0739, AR-C69931MX and MRS2359) have better antagonistic activity and produce analgesic pharmacological properties. Therefore, in this article, we discussed the role of the P2Y12 receptor in different chronic pains and its use as a pharmacological target for pain relief.

G protein-coupled P2Y12 receptor is involved in the progression of neuropathic pain.

The pathological mechanism of neuropathic pain is complex, which seriously affects the physical and mental health of patients, and its treatment is also difficult. The role of G protein-coupled P2Y12 receptor in pain has been widely recognized and affirmed. After nerve injury, stimulated cells can release large amounts of nucleotides into the extracellular matrix, act on P2Y12 receptor. Activated P2Y12 receptor activates intracellular signal transduction and is involved in the development of pain. P2Y12 receptor activation can sensitize primary sensory neurons and receive sensory information. By transmitting the integrated information through the dorsal root of the spinal cord to the secondary neurons of the posterior horn of the spinal cord. The integrated information is then transmitted to the higher center through the ascending conduction tract to produce pain. Moreover, activation of P2Y12 receptor can mediate immune cells to release pro-inflammatory factors, increase damage to nerve cells, and aggravate pain. While inhibits the activation of P2Y12 receptor can effectively relieve pain. Therefore, in this article, we described P2Y12 receptor antagonists and their pharmacological properties. In addition, we explored the potential link between P2Y12 receptor and the nervous system, discussed the intrinsic link of P2Y12 receptor and neuropathic pain and as a potential pharmacological target for pain suppression.

ATP ion channel P2X purinergic receptors in inflammation response.

Different studies have confirmed that P2X purinergic receptors play a key role in inflammation. Activation of P2X purinergic receptors can release inflammatory cytokines and participate in the progression of inflammatory diseases. In an inflammatory microenvironment, cells can release a large amount of ATP to activate P2X receptors, open non-selective cation channels, activate multiple intracellular signaling, release multiple inflammatory cytokines, amplify inflammatory response. While P2X4 and P2X7 receptors play an important role in the process of inflammation. P2X4 receptor can mediate the activation of microglia involved in neuroinflammation, and P2X7 receptor can mediate different inflammatory cells to mediate the progression of tissue-wide inflammation. At present, the role of P2X receptors in inflammatory response has been widely recognized and affirmed. Therefore, in this paper, we discussed the role of P2X receptors-mediated inflammation. Moreover, we also described the effects of some antagonists (such as A-438079, 5-BDBD, A-804598, A-839977, and A-740003) on inflammation relief by antagonizing the activities of P2X receptors.

AKT/GSK-3beta/VEGF signaling is involved in P2RY2 activation-induced the proliferation and metastasis of gastric cancer.

Studies have revealed the contribution of ATP-G-protein-coupled P2Y2 receptor (P2RY2) in tumor progression, but the role of P2RY2 in regulating the progression of gastric cancer (GC) and related molecular mechanisms are relatively lacking. Therefore, this study investigates the effects of P2RY2 on the proliferation and migration of GC through in vivo and in vitro experiments. The results showed that P2RY2 was expressed in GC tissues and GC cell lines. Adenosine triphosphate (ATP) increased the calcium influx in AGS and HGC-27 cells, and was dose-dependent with ATP concentration. ATP and UTP increased the intracellular glycogen content, enhanced the actin fiber stress response, and promoted the proliferation and migration of GC cells, while P2RY2 competitive antagonist AR-C118925XX reversed the changes induced by ATP. Knockdown of P2RY2 expression by shRNA inhibited the proliferation of GC cells. Activation of P2RY2 increased the expression of Snail, Vimentin, and ß-catenin in GC cells, and down-regulated the expression of E-cadherin, while AR-C118925XX decreased the expression of these genes induced by ATP. Activation of P2RY2 activated AKT/GSK-3beta/VEGF signal to promote the proliferation of GC cells, and the P13/AKT signaling pathway LY294002 reversed the corresponding phenomenon, but no synergistic pharmacological properties of AR-C118925XX and LY294002 have been found. In vivo experiments showed that ATP-induced tumor growth, while AR-C118925XX inhibited ATP-induced tumor growth. Our conclusion is that P2RY2 activated the AKT/GSK-3beta/VEGF signal to promote the proliferation and migration of GC, suggesting that P2RY2 may be a new potential target for the treatment of GC.

Blood hemoglobin A1c might predict adverse differences in heart rate variability in a diabetic population: Evidence from the Midlife in the United States (MIDUS) study.

Background: Cardiac autonomic neuropathy in population with diabetes mellitus (DM) is frequent and linked with high risk of cardiovascular mortality. However, studies on whether blood hemoglobin A1c (HbA1c) levels are related to adverse differences in heart rate variability (HRV) in individuals with DM are scarce. Aim: We aimed to investigate the association of blood HbA1c levels with adverse differences in HRV, which is an indicator of cardiac autonomic control, in adult individuals with and without DM. Methods: Data were collected from the Midlife in the United States (MIDUS) study, and 928 individuals were analyzed for the relationship between blood HbA1c levels and HRV through a cross-sectional analysis. Results: Participants with DM had significantly higher HRV than those without DM. The smooth curve suggested inverse relationships between blood HbA1c levels and HF- and LF-HRV seen in participants with DM but not in those without DM after controlling for all covariates (age, sex, BMI, smoking, number of drinking years and exercise). Furthermore, linear regression analysis demonstrated that elevated blood HbA1c levels did contribute to adverse differences in HF-HRV (Sß= -0.118; 95% CI -0.208, -0.027; P=0.012) and LF-HRV (Sß= -0.097; 95% CI -0.177, -0.017; P=0.019) after controlling for these covariates in participants with DM, while in participants without DM, blood HbA1c was not significantly related to adverse differences in HF-HRV (Sß=0.095; 95% CI -0.059, 0.248; P=0.228) or LF-HRV (Sß=0.043; 95% CI -0.103, 0.189; P=0.565). DM has a significant modifying effect on associations between blood HbA1c and adverse differences in HF-HRV (P for interaction=0.019) and LF-HRV (P for interaction=0.029). Conclusions: We reported strong evidence that elevated blood levels of HbA1c were associated with adverse differences in HRV in the diabetic population but not in the nondiabetic population. This finding supported that long-term hyperglycemia is related to autonomic nerve injury in the diabetic population. Blood HbA1c might be a good indicator of cardiac autonomic neuropathy.

Contribution of P2X purinergic receptor in cerebral ischemia injury.

The development of cerebral ischemia involves brain damage and abnormal changes in brain function, which can cause neurosensory and motor dysfunction, and bring serious consequences to patients. P2X purinergic receptors are expressed in nerve cells and immune cells, and are mainly expressed in microglia. The P2X4 and P2X7 receptors in the P2X purinergic receptors play a significant role in regulating the activity of microglia. Moreover, ATP-P2X purine information transmission is involved in the progression of neurological diseases, including the release of pro-inflammatory factors, driving factors and cytokines after cerebral ischemia injury, inducing inflammation, and aggravating cerebral ischemia injury. P2X receptors activation can mediate the information exchange between microglia and neurons, induce neuronal apoptosis, and aggravate neurological dysfunction after cerebral ischemia. However, inhibiting the activation of P2X receptors, reducing their expression, inhibiting the activation of microglia, and has the effect of protecting nerve function. In this paper, we discussed the relationship between P2X receptors and nervous system function and the role of microglia activation inducing cerebral ischemia injury. Additionally, we explored the potential role of P2X receptors in the progression of cerebral ischemic injury and their potential pharmacological targets for the treatment of cerebral ischemic injury.

P2X7 receptor in inflammation and pain.

Different studies have confirmed P2X7 receptor-mediated inflammatory mediators play a key role in the development of pain. P2X7 receptor activation can induce the development of pain by mediating the release of inflammatory mediators. In view of the fact that P2X7 receptor is expressed in the nervous system and immune system, it is closely related to the stability and maintenance of the nervous system function. ATP activates P2X7 receptor, opens non-selective cation channels, activates multiple intracellular signaling, releases multiple inflammatory cytokines, and induces pain. At present, the role of P2X7 receptor in inflammatory response and pain has been widely recognized and affirmed. Therefore, in this paper, we discussed the pathological mechanism of P2X7 receptor-mediated inflammation and pain, focused on the internal relationship between P2X7 receptor and pain. Moreover, we also described the effects of some antagonists on pain relief by inhibiting the activities of P2X7 receptor. Thus, targeting to inhibit activation of P2X7 receptor is expected to become another potential target for the relief of pain.

Icariside II protects cardiomyocytes from hypoxia­induced injury by upregulating the miR­7­5p/BTG2 axis and activating the PI3K/Akt signaling pathway.

Icariside II (ICS II) has been reported to have protective effects against oxidative stress. However, whether ICS II protects cardiomyocytes from myocardial infarction (MI), and the associated underlying mechanisms, remain to be elucidated. Therefore, the current study investigated the effects of ICS II on hypoxia­injured H9c2 cells, as well as the associated molecular mechanisms. A hypoxic injury model was established to emulate the effects of MI. The effects of ICS II on the proliferation of rat cardiomyocyte H9c2 cells were assessed with cell counting kit­8 assays. The apoptotic status of the cells was assessed by flow cytometry, and the expression of apoptosis­related proteins was analyzed by western blotting. A microRNA (miRNA/miR) microarray was used to quantify the differential expression of miRNAs after ICS II treatment, and the levels of miR­7­5p were further quantified by reverse transcription­quantitative PCR. Whether ICS II affected hypoxia­injured cells via miR­7­5p was subsequently examined, and the target of miR­7­5p was also investigated by bioinformatics analysis and luciferase reporter assays. The effects of ICS II on the PI3K/Akt pathway were then evaluated by western blot analysis. Hypoxia treatment decreased viability and the migration and invasion abilities of H9c2 cells, and also induced apoptosis. ICS II significantly increased viability and reduced hypoxia­associated apoptosis. Moreover, ICS II treatment led to the upregulation of miR­7­5p, and the protective effects of ICS II were found to rely on miR­7­5p. Moreover, BTG anti­proliferation factor (BTG2) was identified as a direct target of miR­7­5p, and overexpression of BTG2 inhibited the protective effects of miR­7­5p. Finally, ICS II treatment resulted in the activation of the PI3K/Akt signaling pathway, which is essential for the survival of H9c2 cells under hypoxic conditions. In summary, ICS II reduces hypoxic injury in H9c2 cells via the miR­7­5p/BTG2 axis and activation of the PI3K/Akt signaling pathway.

Rutin suppresses FNDC1 expression in bone marrow mesenchymal stem cells to inhibit postmenopausal osteoporosis.

A previous study revealed that rutin is the main component of Eucommia flavonoids that exerts a protective effect against osteopenia. The bone density and trabecular bone number of osteoporosis model rats can be significantly improved after treatment with rutin. Further study using whole gene expression profiling revealed that FNDC1, a fibronectin type III domain-containing protein, may be a novel bone metabolism-related factor that is decreased in rutin-treated rats. The mechanism underlying the effects of rutin treatment on osteoporosis is important to explore. Micro-CT, western blotting, quantitative PCR, transmission electron microscopy, and Alizarin Red mineralization staining assays were performed to evaluate bone density, FNDC1 expression and autophagy to determine whether FNDC1 might play a significant role in rutin-inhibited trabecular bone loss in rats. FNDC1 expression was high in the osteoporosis group, whereas rutin treatment facilitated FNDC1 downregulation. In addition, rutin promoted bone marrow mesenchymal stem cell autophagy by inhibiting phosphorylated Akt in osteoporosis. In summary, our study shows that rutin could regulate FNCD1 level and autophagy through the Akt/mTOR signaling pathway to provide a novel therapeutic strategy for osteoporosis.

Study of Trichostation A-Induced Expression of Costimulatory Molecules CD80 and CD86 in Acute Myelocytic Leukemia Cells.

OBJECTIVE: To investigate the trichostain A (TSA)-induced expression of costinmulatory molecules CD80 and CD86 in HL-60, K562 and mononuclear cells (MNC) of bone marrow in AML patients and its clinical significance. METHODS: The TSA-induced expression of costimulatory molecules CD80, CD86 in HL-60, K562 and BMMNC, and the cell viability were detected by flow cytometry; the mRNA expression of CD80 and CD86 was detected by RT-PCR; after the TSA-induced HL-60 cells and K562 cells were irradiated with 75 Gy, the effect of these cells on proliferation of PBMNC from healthy volunteers was determined with CCK-8 method. RESULTS: The HL-60 cells and BMMNC in AML patients expressed CD86, not expressed CD80, while the K562 cells not expressed CD86 and CD80. TSA could up-regulate the expression of CD86 in HL-60 cells and BMMNC of AML patients. The TSA-induced HL-60 cells expressing costimulatory molecule CD86 showed the proliferative effect on BMMNC from healthy volunteers. CONCLUSION: The TSA can induce the expression of costimulatory molecule CD86 in HL-60 cells and BMMNC in AML patients, and can improve the proliferation of PBMNC in healthy volunteers.