Anti-inflammatory and DNA Repair Effects of Astragaloside IV on PC12 Cells Damaged by Lipopolysaccharide

Objective This study aimed to establish a neural cell injury model in vitro by stimulating PC12 cells with lipopolysaccharide(LPS)and to examine the effects of astragaloside IV on key targets using high-throughput sequence technology and bioinformatics analyses.Methods PC12 cells in the logarithmic growth phase were treated with LPS at final concentrations of 0.25,0.5,0.75,1,and 1.25 mg/mL for 24 h.Cell morphology was evaluated,and cell survival rates were calculated.A neurocyte inflammatory model was established with LPS treatment,which reached a 50%cell survival rate.PC12 cells were treated with 0.01,0.1,1,10,or 100µmol/L astragaloside IV for 24 h.The concentration of astragaloside IV that did not affect the cell survival rate was selected as the treatment group for subsequent experiments.NOS activity was detected by colorimetry;the expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS and COX-2 mRNA and protein were detected by RT-qPCR and Western blotting.The differentially expressed genes(DEGs)between the groups were screened using a second-generation sequence(fold change>2,P<0.05)with the following KEGG enrichment analysis,RT-qPCR and Western blotting were used to detect the mRNA and protein expression of DEGs related to the IL-17 pathway in different groups of PC12 cells.Results The viability of PC12 cells was not altered by treatment with 0.01,0.1,or 1µmol/L astragaloside IV for 24 h(P>0.05).However,after treatment with 0.5,0.75,1,or 1.25 mg/mL LPS for 24 h,the viability steadily decreased(P<0.01).The mRNA and protein expression levels of ERCC2,XRCC4,XRCC2,TNF-α,IL-1β,TLR4,NOS,and COX-2 were significantly increased after PC12 cells were treated with 1 mg/mL LPS for 24 h(P<0.01);however,these changes were reversed when PC12 cells were pretreated with 0.01,0.1,or 1µmol/L astragaloside IV in PC12 cells and then treated with 1 mg/mL LPS for 24 h(P<0.05).Second-generation sequencing revealed that 1026 genes were upregulated,while 1287 genes were downregulated.The DEGs were associated with autophagy,TNF-α,interleukin-17,MAPK,P53,Toll-like receptor,and NOD-like receptor signaling pathways.Furthermore,PC12 cells treated with a 1 mg/mL LPS for 24 h exhibited increased mRNA and protein expression of CCL2,CCL11,CCL7,MMP3,and MMP10,which are associated with the IL-17 pathway.RT-qPCR and Western blotting analyses confirmed that the DEGs listed above corresponded to the sequence assay results.Conclusion LPS can damage PC12 cells and cause inflammatory reactions in nerve cells and DNA damage.astragaloside IV plays an anti-inflammatory and DNA damage protective role and inhibits the IL-17 signaling pathway to exert a neuroprotective effect in vitro.

Reduction of the oxidative damage to H_(2)O_(2)-induced HepG2 cells via the Nrf2 signalling pathway by plant flavonoids Quercetin and Hyperoside

Hyperoside and quercetin are similar in molecular structures.In this study,the antioxidant regulatory targets of hyperoside and quercetin are mainly in the nuclear factor(erythroid-2-derived)-related factor 2(Nrf2)pathway predicted by network pharmacology.And the antioxidant effect and mechanism of hyperoside and quercetin were measured and compared in H_(2)O_(2)-induced Hep G2 cells and Caenorhabditis elegans.The findings indicated that quercetin was more effective than hyperoside in reducing oxidative damage,which was proved by improved cell viability,decreased reactive oxygen species(ROS)production,decreased cellular apoptosis,and alleviated mitochondrial damage.In addition,quercetin was more efficient than hyperoside in enhancing the expression of Nrf2-associated m RNAs,increasing the activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and catalase(CAT),and reducing the cellular malondialdehyde(MDA)content.Quercetin was superior to hyperoside in prolonging the lifespan of worms,decreasing the accumulation of lipofuscin,inhibiting ROS production,and increasing the proportion of skn-1 in the nucleus.With the Nrf2 inhibitor ML385,we verified that quercetin and hyperoside primarily protected the cells against oxidative damage via the Nrf2 signalling pathway.Furthermore,molecular docking and dynamics simulations demonstrated that the quercetin-Kelch-like ECH-associated protein 1(Keap1)complex was more stable than the hyperoside-Keap1 complex.The stable structure of the complex might hinder the binding of Nrf2 and Keap1 to release Nrf2 and facilitate its entry into the nucleus to play an antioxidant role.Overall,quercetin had a better antioxidant than hyperoside.

Cholesterol and Sericin as First Aid for Damaged Cells

Cells are surrounded by a double-layered phospholipid cell membrane responsible for the isolation of intracellular contents, active regulation of uptake from the extracellular environment, and intercellular connection and communication. These cell membranes must be intact and functionally active for cell survival and biological functioning. Compromised damage repair mechanisms usually result in impaired cellular homeostasis, leading to early or late problems. Chronic myopathies, certain myocardial diseases, aging, and acute or chronic neurodegenerative diseases (like Parkinson and Alzheimer) are directly related to cell membrane damage. This study examined the effect of a cholesterol-loaded nanoparticle (methyl-beta cyclodextrin) or the silk protein sericin on cell membrane and DNA integrity and cell viability in an in vitro cell damage model (frozen-thawed rabbit sperm cells). The cells were stored in liquid nitrogen (-196°C), thawed in small batches, and treated with cholesterol-loaded cyclodextrin or sericin before incubation at 35°C for 4 hours. Cell membrane integrity, DNA damage, and viability rates were assessed immediately after thawing and after the incubation period. The administration of sericin and cholesterol in a cell damage model increased cell survival and reduced DNA damage over a 4-hour post-thaw incubation period, suggesting their potential use as a “first aid” intervention at the cellular level.

Predictive Factors of Renal Damage during Sickle Cell Disease at the Hematology-Oncology Department of Donka University Hospital

Introduction: Sickle cell disease, which is the most common hereditary hemoglobinopathy in the world, attacks all body systems, particularly the kidneys. The view of this study was to investigate the predictive factors of kidney damage during sickle cell disease. Materials and methods: It was a retrospective, descriptive and analytical study on files of sickle cell patients hospitalized in the Hematology-Oncology Department of Donka University Hospital during a period from January 1, 2016 to December 31, 2019. Records of sickle cell patients with one or more renal abnormalities were retained. Sickle cell patients without kidney damage were also selected for a comparative study. Only patients without sickle cell disease were excluded. Results: Seventy-five (75) medical records were collected during the study period. From these cases, thirteen (13) records with kidney disease were observed, a frequency of 17%. The mean age of patients was 24.2 years for extremes of 10 and 65 years. The sex ratio was 1.6 in favor of men. The SSFA2 form was the most represented with 92%. 24-hour proteinuria was measured in 13 patients between whom 6 patients (46.2%) had a proteinuria level ≤ 1 g. Eight (8) patients (61.5%) were in stage 1 of chronic kidney disease. The most common type of renal involvement was tubulo-interstitial nephropathy with 8 patients (61.5%). Bivariate analysis showed that elevated serum creatinine (P 2 form of the sickness (P Conclusion: After the observation of an increased serum creatinine and urea, a predominance observation of the SSFA2 form, it should be possible to target patients for whom screening for kidney damage should henceforth be systematic.

Procyanidin A_1 and its digestive products alleviate acrylamide-induced IPEC-J2 cell damage through regulating Keap1/Nrf2 pathway

Our previous study has revealed that procyanidin A_(1)(A_(1))and its simulated digestive product(D-A,)can alleviate acrylamide(ACR)-induced intestine cell damage.However,the underlying mechanism remains unknown.In this study,we elucidated the molecular mechanism for and D-A_(1) to alleviate ACR-stimulated IPEC-J2 cell damage.ACR slightly activated nuclear factor erythroid 2-related factor 2(Nrf2)signaling and its target genes,but this activation could not reduce intestine cell damage.A_(1) and D-A_(1) could alleviate ACR-induced cell damage,but the effect was abrogated in cells transiently transfected with Nrf2 small interfering RNA(siRNA).Further investigation confirmed that A_(1) and D-A_(1) interacted with Ketch-like ECH-associated protein 1(Keapl),which boosted the stabilization of Nrf2,subsequently promoted the translocation of Nrf2 into the nucleus,and further increased the expression of antioxidant proteins,thereby inhibiting glutathione(GSH)consumption,maintaining redox balance and eventually alleviating ACR-induced cell damage.Importantly,there was no difference between A_(1) and D-A_(1) treated groups,indicating that A_(1) can tolerate gastrointestinal digestion and may be a potential compound to limit the toxicity of ACR.

Lamotrigine protects against cognitive deficits,synapse and nerve cell damage,and hallmark neuropathologies in a mouse model of Alzheimer’s disease

Lamotrigine(LTG)is a widely used drug for the treatment of epilepsy.Emerging clinical evidence suggests that LTG may improve cognitive function in patients with Alzheimer’s disease.However,the underlying molecular mechanisms remain unclear.In this study,amyloid precursor protein/presenilin 1(APP/PS1)double transgenic mice were used as a model of Alzheimer’s disease.Five-month-old APP/PS1 mice were intragastrically administered 30 mg/kg LTG or vehicle once per day for 3 successive months.The cognitive functions of animals were assessed using Morris water maze.Hyperphosphorylated tau and markers of synapse and glial cells were detected by western blot assay.The cell damage in the brain was investigated using hematoxylin and eosin staining.The levels of amyloid-βand the concentrations of interleukin-1β,interleukin-6 and tumor necrosis factor-αin the brain were measured using enzyme-linked immunosorbent assay.Differentially expressed genes in the brain after LTG treatment were analyzed by high-throughput RNA sequencing and real-time polymerase chain reaction.We found that LTG substantially improved spatial cognitive deficits of APP/PS1 mice;alleviated damage to synapses and nerve cells in the brain;and reduced amyloid-βlevels,tau protein hyperphosphorylation,and inflammatory responses.High-throughput RNA sequencing revealed that the beneficial effects of LTG on Alzheimer’s disease-related neuropathologies may have been mediated by the regulation of Ptgds,Cd74,Map3k1,Fosb,and Spp1 expression in the brain.These findings revealed potential molecular mechanisms by which LTG treatment improved Alzheimer’s disease.Furthermore,these data indicate that LTG may be a promising therapeutic drug for Alzheimer’s disease.

A review on cell damage,viability,and functionality during 3D bioprinting

Three-dimensional(3D)bioprinting fabricates 3D functional tissues/organs by accurately depositing the bioink composed of the biological materials and living cells.Even though 3D bioprinting techniques have experienced significant advancement over the past decades,it remains challenging for 3D bioprinting to artificially fabricate functional tissues/organs with high post-printing cell viability and functionality since cells endure various types of stress during the bioprinting process.Generally,cell viability which is affected by several factors including the stress and the environmental factors,such as pH and temperature,is mainly determined by the magnitude and duration of the stress imposed on the cells with poorer cell viability under a higher stress and a longer duration condition.The maintenance of high cell viability especially for those vulnerable cells,such as stem cells which are more sensitive to multiple stresses,is a key initial step to ensure the functionality of the artificial tissues/organs.In addition,maintaining the pluripotency of the cells such as proliferation and differentiation abilities is also essential for the 3D-bioprinted tissues/organs to be similar to native tissues/organs.This review discusses various pathways triggering cell damage and the major factors affecting cell viability during different bioprinting processes,summarizes the studies on cell viabilities and functionalities in different bioprinting processes,and presents several potential approaches to protect cells from injuries to ensure high cell viability and functionality.

Low-Dose Gamma Radiation Fields Decrease Cell Viability, Damage DNA, and Increase the Expression of Hsp70 and p53 Proteins in Human Leukocytes

Ionizing radiations are tools in diagnosis and treatment of diseases. Leukopenia from exposure to ionizing radiation has been reported. Due to their radiosensitivity, leukocytes are a biological model to analyze cell damage. Therefore, cell viability, DNA damage, and Hsp70 and p53 expression in human leukocytes exposed to low-dose gamma radiation fields from a 137Cs source were evaluated. A decrease in cell viability, DNA damage and an increase in the expression of Hsp70 and p53 proportional to the radiation dose received was found, which was 0.2, 0.4, 0.6, 0.8 and 1.0 mGy.

Study of elastic-plastic damage model of cement consolidated soil with high organic content

On the basis of elastic-plastic damage model of cement consolidated soil,the authors took organic contents into reasonable damage variable evolution equation in order to seek relation between the organic contents and parameters in the equation,and established the elastic-plastic damage model of cement consolidated soil considering organic contents.The results show that the parameters change correspondingly with difference of the organic contents.The higher the organic contents are,the less the valves of the parameters such as elastic modulus(E),material parameters(K,n) and damage evolution parameter(ε) become,but the larger strain damage threshold value(εd) of the sample is.Meanwhile,the calculation results obtained from established model are compared with the test data in the condition of common indoors test,which is testified with reliability.

Single Cell Gel Electrophoresis Assay of Porcine Leydig Cell DNA Damage Induced by Zearalenone

[Objective] This study aimed to investigate the effect of zearalenone (ZEN) on DNA damage of porcine leydig cells. [Method] Porcine leydig cells cultured in vitro were collected to determine the median lethal dose (LD50) of ZEN with tetrazolium-based colorimetric assay (MTT assay). Comet assay was carried out to detect the DNA damage of porcine leydig cells exposed to at 0 (negative group), 1, 5, 10, 20, 40 μmol/L of ZEN. [Result] The percentage of cell tail was 16.67%, 34.00%, 40.67%, 52.00% and 64.67% under 0, 1, 5, 10 and 20 μmol/L of ZEN, respectively; the differences between the percentages of cell tail in various experimental groups had extremely significant statistical significance compared with the negative group (P<0.01), showing a significant dose-effect relationship; Tail length in various groups was 57.60±4.78, 57.75±6.25, 78.97±5.83, 100.50±6.94 and 146.83±12.31 μm, respectively; Tail DNA % in various groups was 21.29±2.25%, 22.24±2.43%, 31.21±6.27%, 37.45±4.33% and 60.68±9.83%, respectively; Tail length and Tail DNA % in experimental groups with ZEN concentration above 5 μmol/L showed significant differences (P<0.05) compared with the negative group, which showed an upward trend with the increase of ZEN concentration. [Conclusion] ZEN has genotoxic effect on porcine leydig cells, which can cause DNA damage, with a significant dose-effect relationship.

Effects of Nitrobenzenes on DNA Damage in Germ Cells of Rats

The single cell gel electrophoresis （SCGE） technique was used to detect DNA damage in germ cells of rats, which was induced by five tested nitroaromatic compounds. Mixed cultures of Sertoli and germ cells were prepared from the rats testis and their responses to rn-dinitrobenzene （ m-DNB）, 2,4-dinitrotoluene （ 2,4-DNT）, 2,6-dinitroto-luene（2,6-DNT）, 4-nitrotoluene（4-NT） and 2,4-dinitroaniline（2,4-DNAn） were studied. The results show that all the five chemicals have a reproductive toxicity. Each dose group and the control group were significantly different （ P 〈 0. 01 ）. All of them can lead to the damage to DNA in the germ cells of Kunming male rats in the definite range of concentration（m-DNB ： 0. 04-25μmol/L; 2,4-DNT, 2,6-DNT and 4-NT： 0. 032-500μmol/L; 2,4-DNAn ：0. 8-20μmol/L）. When the concentration increases, the damage rate will become higher, which shows an evident logarithm dose-effect relationship.

DNA damage,apoptosis and cell cycle changes induced by fluoride in rat oral mucosal cells and hepatocytes

AIM： To study the effect of fluoride on oxidative stress, DNA damage and apoptosis as well as cell cycle of rat oral mucosal cells and hepatocytes.METHODS： Ten male SD rats weighing 80N120 g were randomly divided into control group and fluoride group, 5 animals each group. The animals in fluoride group had free access to deionized water containing 150 mg/L sodium fluoride （NaF）. The animals in control group were given distilled water. Four weeks later, the animals were killed. Reactive oxygen species （ROS） in oral mucosa and liver were measured by Fenton reaction, lipid peroxidation product, malondialdehyde （MDA）, was detected by thiobarbituric acid （TBA） reaction, reduced glutathione （GSH） was assayed by dithionitrobenzoic acid （DTNB） reaction. DNA damage in oral mucosal cells and hepatocytes was determined by single cell gel （SCG） electrophoresis or comet assay. Apoptosis and cell cycle in oral mucosal cells and hepatocytes were detected by flow cytometry.RESULTS： The contents of ROS and MDA in oral mucosa and liver tissue of fluoride group were significantly higher than those of control group （P〈 0.01）, but the level of GSH was markedly decreased （P〈 0.01）. The contents of ROS, MDA and GSH were （134.73 ＋ 12.63） U/mg protein, （1.48 ＋ 0.13） mmol/mg protein and （76.38 ~ 6.71） mmol/ mg protein in oral mucosa respectively, and （143.45＋ 11.76） U/mg protein, （1.44：1：0.12） mmol/mg protein and （78.83±7.72） mmol/mg protein in liver tissue respectively. The DNA damage rate in fluoride group was 50.20% in oral mucosal cells and 44.80% in hepatocytes, higher than those in the control group （P 〈0.01）. The apop- tosis rate in oral mucosal cells was （13.63 ＋ 1.81） % in fluoride group, and （t2.76＋ 1.67） % in hepatocytes, higher than those in control group. Excess fluoride could differently lower the number of oral mucosal cells and hepatocytes at G0/G1 and S G2/M phases （P〈 0.05）.CONCLUSION： Excess fluoride can induce oxidative stress and DNA damage and lead to apoptosis and cell cycle change in rat oral mucosal cells and hepatocytes.

Hyperbaric oxygen treatment promotes neural stem cell proliferation in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage

Hyperbaric oxygen therapy for the treatment of neonatal hypoxic-ischemic brain damage has been used clinically for many years, but its effectiveness remains controversial. In addition, the mechanism of this potential neuroprotective effect remains unclear. This study aimed to investigate the influence of hyperbaric oxygen on the proliferation of neural stem cells in the subventricular zone of neonatal Sprague-Dawley rats （7 days old） subjected to hypoxic-ischemic brain damage. Six hours after modeling, rats were treated with hyperbaric oxygen once daily for 7 days. Immunohistochemistry revealed that the number of 5-bromo-2＇-deoxyuridine positive and nestin positive cells in the subventricular zone of neonatal rats increased at day 3 after hypoxic-ischemic brain damage and peaked at day 5. After hyperbaric oxygen treatment, the number of 5-bromo-2＇- deoxyuddine positive and nestin positive cells began to increase at day 1, and was significantly higher than that in normal rats and model rats until day 21. Hematoxylin-eosin staining showed that hyperbaric oxygen treatment could attenuate pathological changes to brain tissue in neonatal rats, and reduce the number of degenerating and necrotic nerve cells. Our experimental findings indicate that hyperbaric oxygen treatment enhances the proliferation of neural stem cells in the subventricular zone of neonatal rats with hypoxic-ischemic brain damage, and has therapeutic potential for promoting neurological recovery following brain injury.

Transplantation of vascular endothelial growth factor-modified neural stem/progenitor cells promotes the recovery of neurological function following hypoxic-ischemic brain damage

Neural stem/progenitor cell （NSC） transplantation has been shown to effectively improve neurological function in rats with hypoxic-isch- emic brain damage. Vascular endothelial growth factor （VEGF） is a signaling protein that stimulates angiogenesis and improves neural regeneration. We hypothesized that transplantation of VEGF-transfected NSCs would alleviate hypoxic-ischemic brain damage in neo- natal rats. We produced and transfected a recombinant lentiviral vector containing the VEGF165gene into cultured NSCs. The transfected NSCs were transplanted into the left sensorimotor cortex of rats 3 days after hypoxic-ischemic brain damage. Compared with the NSCs group, VEGF mRNA and protein expression levels were increased in the transgene NSCs group, and learning and memory abilities were significantly improved at 30 days. Furthermore, histopathological changes were alleviated in these animals. Our findings indicate that transplantation of VEGF-transfected NSCs may facilitate the recovery of neurological function, and that its therapeutic effectiveness is better than that of unmodified NSCs.

Low-dose testosterone treatment decreases oxidative damage in TM3 Leydig cells

Testosterone replacement therapy has benefits for aging men and those with hypogonadism. However, the effects of exogenous testosterone on Leydig cells are still unclear and need to be clarified. In this report, we demonstrate that testosterone supplementation can reduce oxidative damage in Leydig cells. The TM3 Leydig cell line was used as an in vitrocell model in this study. Cytoprotective effects were identified with 100-nmol l-1 testosterone treatment, but cytotoxic effects were found with ≥ 500-nmol l-1 testosterone supplementation. Significantly reduced reactive oxygen species （ROS） generation, lipid peroxide contents and hypoxia induction factor （HIF）-lα stabilization and activation were found with lO0-nmol 1-1 testosterone treatment. There was a 1.72-fold increase in ROS generation in the 500-nmol l-1 compared to the lO0-nmol l-1 testosterone treatment. A 1.58-fold increase in steroidogenic acute regulatory protein （STAR） expression was found in 50-nmol l-1 testosterone-treated cells （P〈0.01）. Chemically induced hypoxia was attenuated by testosterone supplementation. Leydig cells treated with low-dose testosterone supplementation showed cytoprotection by decreasing ROS and lipid peroxides, increasing StAR expression and relieving hypoxia stress as demonstrated by HIF-1α stabilization. Increased oxidative damage was found with ≥ 500-nmol l-1 testosterone manipulation. The mechanism governing the differential dose effects of testosterone on Leydig cells needs further investigation in order to shed light on testosterone replacement therapy.

Autophagy occurs within an hour of adenosine triphosphate treatment after nerve cell damage:the neuroprotective effects of adenosine triphosphate against apoptosis

After hypoxia, ischemia, or inflammatory injuries to the central nervous system, the damaged cells release a large amount of adenosine triphosphate, which may cause secondary neuronal death. Autophagy is a form of cell death that also has neuroprotective effects. Cell Counting Kit assay, monodansylcadaverine staining, flow cytometry, western blotting, and real-time PCR were used to determine the effects of exogenous adenosine triphosphate treatment at different concentrations （2, 4, 6, 8, 10 mmol/L） over time （1, 2, 3, and 6 hours） on the apoptosis and autophagy of SH-SY5Y cells. High concentrations of extracellular adenosine triphosphate induced autophagy and apoptosis of SH-SYSY cells. The enhanced autophagy first appeared, and peaked at 1 hour after treatment with adenosine triphosphate. Cell apoptosis peaked at 3 hours, and persisted through 6 hours. With prolonged exposure to the adenosine triphosphate treatment, the fraction of apoptotic cells increased. These data suggest that the SH-SY5Y neural cells initiated autophagy against apoptosis within an hour of adenosine triphosphate treatment to protect themselves against injury.

DNA damage responses in cancer stem cells: Implications for cancer therapeutic strategies

The identification of cancer stem cells(CSCs) that are responsible for tumor initiation, growth, metastasis, and therapeutic resistance might lead to a new thinking on cancer treatments. Similar to stem cells,CSCs also display high resistance to radiotherapy and chemotherapy with genotoxic agents. Thus, conventional therapy may shrink the tumor volume but cannot eliminate cancer. Eradiation of CSCs represents a novel therapeutic strategy. CSCs possess a highly efficient DNA damage response(DDR) system, which is considered as a contributor to the resistance of these cells from exposures to DNA damaging agents. Targeting of enhanced DDR in CSCs is thus proposed to facilitate the eradication of CSCs by conventional therapeutics. To achieve this aim, a better understanding of the cellular responses to DNA damage in CSCs is needed. In addition to the protein kinases and enzymes that are involved in DDR, other processes that affect the DDR including chromatin remodeling should also be explored.

One-step cell biomanufacturing platform:porous gelatin microcarrier beads promote human embryonic stem cell-derived midbrain dopaminergic progenitor cell differentiation in vitro and survival after transplantation in vivo

Numerous studies have shown that cell replacement therapy can replenish lost cells and rebuild neural circuitry in animal models of Parkinson’s disease.Transplantation of midbrain dopaminergic progenitor cells is a promising treatment for Parkinson’s disease.However,transplanted cells can be injured by mechanical damage during handling and by changes in the transplantation niche.Here,we developed a one-step biomanufacturing platform that uses small-aperture gelatin microcarriers to produce beads carrying midbrain dopaminergic progenitor cells.These beads allow midbrain dopaminergic progenitor cell differentiation and cryopreservation without digestion,effectively maintaining axonal integrity in vitro.Importantly,midbrain dopaminergic progenitor cell bead grafts showed increased survival and only mild immunoreactivity in vivo compared with suspended midbrain dopaminergic progenitor cell grafts.Overall,our findings show that these midbrain dopaminergic progenitor cell beads enhance the effectiveness of neuronal cell transplantation.

Protective effects of MCI-186 on oxidative damage in a cell model of Alzheimer's disease

Oxidative stress has an important role in the development of Alzheimer＇s disease （AD）. Beta amyloid protein 25-35 （Aβ25-35） can generate oxygen free radicals, and MCI-186 （3-methyl-l-phenyl-2-pyrazolin-5-one, edaravone） can specifically eliminate hydroxyl radicals. The present study introduced Aβ25-35 into PC12 cells to establish a cell model of AD, and investigated the neuroprotective effects of MCI-186 on AD. Results showed that MCI-186 had a positive effect on the prevention and treatment of AD by inhibiting protein oxidative products, advanced glycation end products, lipid oxidative end products and DNA oxidative damage in PC12 cells induced by Aβ25-35.

Prevention of central cell damage to isolated islets of Langerhans in hamsters by low temperature preconditioning

BACKGROUND: The efficacy of clinical islet transplanta- tion has been demonstrated with autografts, and although islet allografts have established insulin independence in a small number of IDDM patients, the treatment is con- founded by the necessity of central cell damage immuno- suppression, the lack of donor tissue, and recurring islet immunogenicity. These limitations underscore a need to develop therapies to serve the large population of diabetic patients. This study was designed to document central cell damage to isolated islets of Langerhans in hamsters and its prevention. METHODS: Islets were cultured at 37 °C for 7-14 days after isolation, and then at 26 °C for 2,4 and 7 days before addi- tional culture at 37 °C for an additional 7 days. Central cell damage in the isolated islets was monitored by video-mi- croscopy and analyzed quantitatively by a computer-assis- ted image analysis system. The analysis included daily measurement of the diameter and the area of the isolated is- lets and the area of the central cell damage that developed in those islets over time during culture. Histological exami- nation and TdT-mediated dUTP-biotin nick end labeling (TUNEL) assay were used to characterize cell damage and to monitor islet function. RESULTS; Microscopic analysis showed that during the 7 to 14 days of culture at 37 °C, central cell damage appeared in the larger islets with diameters greater than 200 μm, which included both necrotic and apoptotic cell death. Low temperature (26 °C) culture prevented central cell damage of isolated islets. The 7-day culture procedure at 26 °C could inhibit most of the central cell ( excluding diameters greater than 300 μm) damage when the islets were re- warmed to 37 °C. CONCLUSIONS: Our results indicate that central cell da- mage to isolated islets of Langerhans correlates with the size of the islets. Low temperature (26 °C) culture can preventcentral cell damage to the isolated islets, and is capable to successfully precondition these islets for 37 °C culture. These novel findings may help to understand the patho- physiology of early loss of islet tissue after transplantation, and may provide a new strategy to improve graft function in the clinical setting of islet transplantation.