Assessment of the effects of intrastromal injection of adipose-derived stem cells in keratoconus patients

·AIM: To evaluate the efficacy and safety of intrastromal transplantation of adipose-derived stem cells(ASCs) in keratoconus patients.·METHODS: This study was conducted on 8 eyes of 8 patients with moderate to severe keratoconus. In the patients, ophthalmic assessments including visual acuity, refraction, slit lamp examination, fundoscopy, corneal topography, and confocal microscopy were performed. Autologous stem cells were used. The isolated stem cells were injected into the corneal stroma by using femtosecond laser. Surgical procedure was similar to intracorneal ring implantation. All patients were re-assessed 1, 3, and 6mo after surgery.·RESULTS: The baseline mean visual acuity was 0.48±0.18 and improved to 0.66±0.17 after surger y and final acuity increased by 1.85±0.80 lines(P=0.001).The mean spherical refraction of patients improved 0.34 ± 0.35 D(P=0.039), and the mean cylindrical refraction of patients improved 0.84±0.23 D(P=0.016). The mean flat keratometry decreased 0.78±0.71 D(P=0.017), and the mean steep keratometry decreased 0.59±0.68 D(P=0.023). The mean central corneal thickness of patients improved of 6.29±4.47 μm(P=0.03). The mean keratocyte density at the anterior and middle stroma of cornea increased(P<0.05) but remained stable at the posterior stroma after 6mo. All patients had no complications and their corneas remained transparent. ·CONCLUSION: Intrastromal transplantation of ASCs has positive effects on vision and refractive parameters in most patients with keratoconus. After six months, visual acuity improved moderately, corneal parameters reduced slightly, and stromal keratocytes density increased. This modality is safe, and patients do not have any complications.

Sox2 enhances the tumorigenicity and chemoresistance of cancer stem-like cells derived from gastric cancer

Gastric cancer stem-like cells（GCSCs） have been identified to possess the ability of self-renewal and tumor initi-ation.However,the mechanisms involved remain largely unknown.Here,we isolated and characterized the GCSCs by side population（SP） sorting procedure and cultured sphere cells（SC） from human gastric cancer cell lines SGC-7901,BGC-823,MGC-803,HGC-27 and MKN-28.The sorting and culture assay revealed that SP cells proliferated in an asymmetric division manner.In addition,SP cells exhibited a higher potential of spheroid colony formation and greater drug resistance than non-SP cells（NSP）.Moreover,the SC were found with enhanced capabilities of drug resistance in vitro and tumorigenicity in vivo.Sox2 mRNA and protein was highly and significantly overex-pressed in the SP cells and SC.Importantly,downregulation of Sox2 with siRNA obviously reduced spheroid colony formation and doxorubicin efflux,as well as increased apoptosis rate in sphere cells in vitro and suppressed tumori-genicity in vivo.These results suggest that both SP cells and cultured SC enrich with GCSCs and that Sox2 plays a pivotal role in sustaining stem cell properties and might be a potential target for gastric cancer therapy.

Hepatocellular carcinoma and non-alcoholic steatohepatitis:The state of play

Hepatocellular carcinoma(HCC) is now the fifth cancer of greatest frequency and the second leading cause of cancer related deaths worldwide. Chief amongst the risks of HCC are hepatitis B and C infection, aflatoxin B1 ingestion, alcoholism and obesity. The latter can promote non-alcoholic fatty liver disease(NAFLD), that can lead to the inflammatory form non-alcoholic steatohepatitis(NASH), and can in turn promote HCC. The mechanisms by which NASH promotes HCC are only beginning to be characterized. Here in this review, we give a summary of the recent findings that describe and associate NAFLD and NASH with the subsequent HCC progression. We will focus our discussion on clinical and genomic associations that describe new risks for NAFLD and NASH promoted HCC. In addition, we will consider novel murine models that clarify some of the mechanisms that drive NASH HCC formation.

Barriers in contribution of human mesenchymal stem cells to murine muscle regeneration

AIM: To study regeneration of damaged human and murine muscle implants and the contribution of added xenogeneic mesenchymal stem cells(MSCs).METHODS: Minced human or mouse skeletal muscle tissues were implanted together with human or mouse MSCs subcutaneously on the back of non-obese diabetic/severe combined immunodeficient mice. The muscle tissues(both human and murine) were minced with scalpels into small pieces(< 1 mm3) and aliquoted in portions of 200 mm3. These portions were either cryopreserved in 10% dimethylsulfoxide or freshly implanted. Syngeneic or xenogeneic MSCs were added to the minced muscles directly before implantation. Implants were collected at 7, 14, 30 or 45 d after transplantation and processed for(immuno)histological analysis. The progression of muscle regeneration was assessed using a standard histological staining(hematoxylin-phloxinsaffron). Antibodies recognizing Pax7 and von Willebrand factor were used to detect the presence of satellite cells and blood vessels, respectively. To enable detection of the bone marrow-derived MSCs or their derivatives we used MSCs previously transduced with lentiviral vectors expressing a cytoplasmic LacZ gene. X-gal staining of the fixed tissues was used to detect β-galactosidase-positive cells and myofibers.RESULTS: Myoregeneration in implants of fresh murine muscle was evident as early as day 7, and progressed with time to occupy 50% to 70% of the implants. Regeneration of fresh human muscle was slower. These observations of fresh muscle implants were in contrast to the regeneration of cryopreserved murine muscle that proceeded similarly to that of fresh tissue except for day 45(P < 0.05). Cryopreserved human muscle showed minimal regeneration, suggesting that the freezing procedure was detrimental to human satellite cells. In fresh and cryopreserved mouse muscle supplemented with LacZ-tagged mouse MSCs, β-galactosidase-positive myofibers were identified early after grafting at the wellvascularized periphery of the implants. The contribution of human MSCs to murine myofiber formation was, however, restricted to the cryopreserved mouse muscle implants. This suggests that fresh murine muscle tissue provides a suboptimal environment for maintenance of human MSCs. A detailed analysis of the histological sections of the various muscle implants revealed the presence of cellular structures with a deviating morphology. Additional stainings with alizarin red and alcian blue showed myofiber calcification in 50 of 66 human muscle implants, and encapsulated cartilage in 10 of 81 of murine muscle implants, respectively.CONCLUSION: In mouse models the engagement of human MSCs in myoregeneration might be underestimated. Furthermore, our model permits the dissection of speciesspecific factors in the microenvironment.

Intracellular Self-assembly of TPE-biotin Nanoparticles Enables Aggregation-Induced Emission Fluorescence for Cancer-Targeted Imaging

Fluorogens with aggregation-induced emission (AIE) characteristics have recently been widely applied for studying biological events, and fluorogens with “smart” properties are especially desirable. Herein, we rationally designed and synthesized a biotinylated and reduction-activatable probe (Cys(StBu)-Lys(biotin)-Lys(TPE)-CBT (1)) with AIE properties for cancer-targeted imaging. The biotinylated probe 1 can be actively uptaken by the biotin receptor-overexpressing cancer cells, and then “smartly” self-assemble into nanoparticles inside cells and turn the fluorescence “On”. Employing this “smart” strategy, we successfully applied probe 1 for cancer-targeted imaging. We envision that this biotinylated intelligent probe 1 might be further developed for cancer-targeted imaging in routine clinical studies in the near future.

Sexual differences of the effects of prenatal stress on the expression of extracellular signal-regulated kinaseas in the hippocampus of offspring rats

BACKGROUND： Prenatal stress has been shown to inhibit cell proliferation in the dentate gyrus and hippocampus, reduce hippocampal volume, and cause neuronal loss and oxidative damage in the hippocampus of offspring rats, but the sexual difference of the effects on offsprings is seldom referred to. OBJECTIVE： To observe the effect of prenatal stress to adult pregnant rats on expression of extracellular signal-regulated kinases （ERK） in hippocampus of the offspring rats of different genders. DESIGN ： A randomized and control animal experiment.SETTING： Department of Physiology and Pathophysiology, School of Medicine, Xi＇an Jiaotong University. MATERIALS ： The experiments were carried out in the Key Laboratory of Environment and Gene Related Diseases （Xi＇an Jiaotong University）, Ministry of Education between October 2005 and March 2006. Fifteen female and five male adult Sprague-Dawley rats were adopted. Female rats weighing 230-250 g and male rats weighing 280-350 g were used. METHODS： The virgin female rats were placed overnight with adult male rats （3：1） for mating. A total of twelve pregnant rats were randomly assigned to prenatal stress group （PNS group, n=6） and control group （n=6）. The pregnant rats of the PNS group were exposed to restraint stress on days 14-20 of pregnancy three times a day, 45 minutes for each time . The restraint device was a transparent plastic tube （6.8 cm in diameter） with air holes for breathing and closed end. The length could be adjusted to accommodate the size of the animals. To prevent habituation of animals to the daily procedure, restraint periods were randomly shifted within certain time periods （8：00-11：00, 11：00-14：00, and 16：00-19：00）. After birth, offsprings of all groups were culled to 8-10 litters in each group and housed in the same animal room, and kept together with their biologic mothers. The pregnant rats of the control group were left undisturbed. On day 21, after all the offspring were weaned, male and female pups were separated and housed four in each cage respectively until test at 30 days of age. At the end of postnatal day 30, one male and female offspring rats from the same dam were selected with a random choice and a total of 24 animals from 12 different dams were used. The experimental rats were sacrificed by decapitation under anesthesia. Bilateral hippocampal tissues were isolated and homogenized in cold condition. Alkaline carbonate buffer （BCA） method was used to detect the concentration of extracellular signal-regulated kinases （ERK）, then mixed with loading buffer, the constant voltage was 100 V. Finally, BCIP/NBT staining and electrDphoresis were performed, the absorbance （A） value for the bands was detected with the Bandscan analytical software, and the expression of ERK in hippocampus of offspring rats of different genders in each group was quantitatively analyzed. MAIN OUTCOME MEASURES： The level of ERK expression in hippocampus of offspring rats of different genders in each group was observed.RESULTS： All the 24 offspring rats were involved in the analysis of results. ① The staining results of ERP activity in the extract of brain tissue detected with Western blotting technique and specific antibody analysis showed that the ERP in hippocampus of offspring rats had two subtypes of ERK-1 and ERK-2, and the latter was the main type.② Standardized by the average A value in the control group, the quantitative data of the general A value of total ERK showed that the expression of ERK-2 in hippocampus of female offspring rats was obviously higher in the PNS group than in the control group （A value： 126±6.76,100±4.89,P〈 0.01）. ③The expression of ERK-2 had no obvious difference between the female and male offspring rats in the control group.④ The expression of ERK-2 in hippocampus of male offspring rats was a little higher in the PNS group than in the control group （A value： 104±6.27,102±5.48,P 〉 0.05）. CONCLUSION ： PNS significantly affects the increase of ERK expression in hippocampus of female offspring rats, but has no obvious influence on that of male ones.

TGF-β signaling in vascular biology and dysfunction

Transforming growth factor （TGF）-β family members are multifunctional cytokines that elicit their effects on cells, including endothelial and mural cells, via specific type I and type II serine/threonine kinase receptors and intracellular Smad transcription factors. Knock-out mouse models for TGF-β family signaling pathway components have revealed their critical importance in proper yolk sac angiogenesis. Genetic studies in humans have linked mutations in these signaling components to specific cardiovascular syndromes such as hereditary hemorrhagic telangiectasia, primary pulmonary hypertension and Marfan syndrome. In this review, we present recent advances in our under- standing of the role of TGF-β receptor signaling in vascular biology and disease, and discuss how this may be applied for therapy.

Prognostic value of perioperative leukocyte count in resectable gastric cancer

AIM: To investigate the prognostic significance of perioperative leukopenia in patients with resected gastric cancer.METHODS: A total of 614 eligible gastric cancer patients who underwent curative D2 gastrectomy and adjuvant chemotherapy were enrolled in this study. The relationship between pre- and postoperative hematologic parameters and overall survival was assessed statistically, adjusted for known prognostic factors.RESULTS: The mean white blood cell count(WBC) significantly decreased after surgery, and 107/614(17.4%) patients developed p-leukopenia, which was defined as a preoperative WBC ≥ 4.0 × 109/L and postoperative WBC < 4.0 × 109/L, with an absolute decrease ≥ 0.5 × 109/L. The neutrophil count decreased significantly more than the lymphocyte count. P-leukopenia significantly correlated with poor tumor differentiation and preoperative WBC. A higher preoperative WBC and p-leukopenia were independent negative prognostic factors for survival [hazard ratio(HR) = 1.602, 95% confidence interval(CI): 1.185-2.165; P = 0.002, and HR = 1.478, 95%CI: 1.149-1.902; P = 0.002, respectively] after adjusting for histology, Borrmann type, p TNM stage, vascular or neural invasion, gastrectomy method, resection margins, chemotherapy regimens, and preoperative WBC count. The patients with both higher preoperative WBC and p- leukopenia had a worse prognosis compared to those with lower baseline WBC and no p-leukopenia(27.5 mo vs 57.3 mo, P < 0.001). CONCLUSION: Preoperative leukocytosis alone or in combination with postoperative leukopenia could be independent prognostic factors for survival in patients with resectable gastric cancer.

Relevance of α-defensins(HNP1-3) and defensin β-1 in diabetes

AIM: To investigate the genetic background of human defensin expression in type 1 and 2 diabetes.

ABC transporters,neural stem cells and neurogenesis - a different perspective

Stem cells intrigue. They have the ability to divide exponentially, recreate the stem cell compartment, as well as create differentiated cells to generate tissues. Therefore, they should be natural candidates to provide a renewable source of cells for transplantation applied in regenerative medicine. Stem cells have the capacity to generate specific tissues or even whole organs like the blood, heart, or bones. A subgroup of stem cells, the neural stem cells （NSCs）, is characterized as a self-renewing population that generates neurons and glia of the developing brain. They can be isolated, genetically manipulated and differentiated in vitro and reintroduced into a developing, adult or a pathologically altered central nervous system. NSCs have been considered for use in cell replacement therapies in various neurodegenerative diseases such as Parkinson＇s disease and Alzheimer＇s disease. Characterization of genes with tightly controlled expression patterns during differentiation represents an approach to understanding the regulation of stem cell commitment. The regulation of stem cell biology by the ATP-binding cassette （ABC） transporters has emerged as an important new field of investigation. As a major focus of stem cell research is in the manipulation of cells to enable differentiation into a targeted cell population; in this review, we discuss recent literatures on ABC transporters and stem cells, and propose an integrated view on the role of the ABC transporters, especially ABCA2, ABCA3, ABCB 1 and ABCG2, in NSCs＇ proliferation, differentiation and regulation, along with comparisons to that in hematopoietic and other stem cells.

Phylogenetic relationship and genetic differentiation of Populus caspica and Populus alba using cpDNA and ITS noncoding sequences

Populus caspica Bornm.(section Leuce and subsection Albida), one of the most endangered endemic tree species in the Hyrcanian Forest in Iran, has numerous morphological characteristics that are closely similar to Populus alba; to clarify their taxonomic relatedness and genetic differentiation and thus inform conservation strategies, we used the noncoding regions of chloroplast DNA(cpDNA; trnL-F and trnH-psbA) and the internal transcribed spacer(ITS). Leaf samples were collected from six populations across northern Iran. cpDNA and ITS fragments were amplified by universal primers using the PCR technique and directed sequencing. The results showed that P. caspica is genetically differentiated from P.alba, and two ITS variants were detected within some P.caspica individuals. Conflicts between topologies from ITS and plastid genomes were observed. High differentiation of P. caspica from the other Populus species shown in this study confirmed the diverging taxonomic status of this endangered species. We recommend in situ conservation measures(e.g., protected areas) for at least several populations of this species, especially in the plain regions of the Hyrcanian forest.

Effect of Tumor Necrosis Factor-α on Acyl Coenzyme A: Cholesteryl Acyltransferase Activity and ACAT1 Gene Expression in THP-1 Macrophages

In order to explore the effect and mechanisms of tumor necrosis factor-α （TNF-α） on the activity of the acyl coenzyme A： cholesteryl acyltransferase （ACAT）, THP-I monocytes were cul- tured and induced to differentiate into macrophages with phorbol ester. TNF-α （60 ng/mL） was added at different time points into the macrophage-containing medium and the ACAT enzyme activity was measured by quantifying the incorporation of [1-^14C] oleoyl CoA into cholesteryl esters. The expression of ACAT-1 protein and mRNA was respectively detected by Western blotting and RT-PCR in THP-1 macrophages 24 h after treatment with TNF-α （60 ng/mL）. The results indicated that ACAT activity in THP-I macrophages treated with TNF-α was increased in a time-dependent manner. The expression levels of ACAT-1 protein and mRNA were significantly increased in THP-I macrophages after treatment with TNF-α （P〈0.05）. It was suggested that TNF-α could increase the activity of ACAT in THP-1 macrophages by up-regulating the expression of ACAT-1 gene.

SHP2 regulates skeletal cell fate by modifying SOX9 expression and transcriptional activity

Chondrocytes and osteoblasts differentiate from a common mesenchymal precursor, the osteochondroprogenitor（OCP）, and help build the vertebrate skeleton. The signaling pathways that control lineage commitment for OCPs are incompletely understood. We asked whether the ubiquitously expressed protein-tyrosine phosphatase SHP2（encoded by Ptpn11） affects skeletal lineage commitment by conditionally deleting Ptpn11 in mouse limb and head mesenchyme using ＂Cre-lox P＂-mediated gene excision.SHP2-deficient mice have increased cartilage mass and deficient ossification, suggesting that SHP2-deficient OCPs become chondrocytes and not osteoblasts. Consistent with these observations, the expression of the master chondrogenic transcription factor SOX9 and its target genes Acan, Col2a1, and Col10a1 were increased in SHP2-deficient chondrocytes, as revealed by gene expression arrays, q RT-PCR, in situ hybridization, and immunostaining. Mechanistic studies demonstrate that SHP2 regulates OCP fate determination via the phosphorylation and SUMOylation of SOX9, mediated at least in part via the PKA signaling pathway. Our data indicate that SHP2 is critical for skeletal cell lineage differentiation and could thus be a pharmacologic target for bone and cartilage regeneration.

Embryonic stem cell-derived neural progenitors as non-tumorigenic source for dopaminergic neurons

AIM:To find a safe source for dopaminergic neurons,we generated neural progenitor cell lines from human embryonic stem cells.METHODS:The human embryonic stem(hES)cell line H9 was used to generate human neural progenitor(HNP)cell lines.The resulting HNP cell lines were differentiated into dopaminergic neurons and analyzed by quantitative real-time polymerase chain reaction and immunofluorescence for the expression of neuronal differentiation markers,including beta-III tubulin(TUJ1)and tyrosine hydroxylase(TH).To assess the risk of teratoma or other tumor formation,HNP cell lines and mouse neuronal progenitor(MNP)cell lines were injected subcutaneously into immunodeficient SCID/beige mice.RESULTS:We developed a fairly simple and fast protocol to obtain HNP cell lines from hES cells.These cell lines,which can be stored in liquid nitrogen for several years,have the potential to differentiate in vitro into dopaminergic neurons.Following day 30 of differentiation culture,the majority of the cells analyzed expressed the neuronal marker TUJ1 and a high proportion of these cells were positive for TH,indicating differentiation into dopaminergic neurons.In contrast to H9 ES cells,the HNP cell lines did not form tumors in immunodeficient SCID/beige mice within 6 mo after subcutaneous injection.Similarly,no tumors developed after injection of MNP cells.Notably,mouse ES cells or neuronal cells directly differentiated from mouse ES cells formed teratomas in more than 90%of the recipients.CONCLUSION:Our findings indicate that neural progenitor cell lines can differentiate into dopaminergic neurons and bear no risk of generating teratomas or other tumors in immunodeficient mice.

Hepatocyte cytoskeleton during ischemia and reperfusion -influence of ANP-mediated p38 MAPK activation

AIM： To determine functional consequences of this activation, whereby we focused on a potential regulation of the hepatocyte cytoskeleton during ischernia and reperfusion. METHODS： For in vivo experiments, animals received ANP （5 μg/kg） intravenously. In a different experimental setting, isolated rat livers were perfused with KH-buffer ＋ANP （200 nmol/L）＋SB203580 （2 μmol/L）. Livers were then kept under ischernic conditions for 24 h, and either transplanted or reperfused. Actin, Hsp27, and phosphorylated Hsp27 were determined by Western blotting, p38 MAPK activity by in vitro phosphorylation assay. F-actin distribution was determined by confocal microscopy. RESULTS： We first confirmed that ANP preconditioning leads to an activation of p38 MAPK and observed alterations of the cytoskeleton in hepatocytes of ANP- preconditioned organs. ANP induced an increase of hepatic F-actin after ischemia, which could be prevented by the p38 MAPK inhibitor SB203580 but had no effect on bile flow. After ischemia untreated livers showed a translocation of Hsp27 towards the cytoskeleton and an increase in total Hsp27, whereas ANP preconditioning prohibited translocation but caused an augmentation of Hsp27 phosphorylation. This effect is also mediated via p38 MAPK, since it was abrogated by the p38 MAPK inhibitor SB203580. CONCLUSION： This study reveals that ANP-mediated p38 MAPK activation leads to changes in hepatocyte cytoskeleton involving an elevation of phosphorylated Hsp27 and thereby for the first time shows functional consequences of ANP-induced hepatic p38 MAPK activation.

Synthetic Lethality Induced by a Strong <i>Drosophila</i>Enhancer of Expanded Polyglutamine Tract

Proteins containing an expanded polyglutamine tract are neurotoxins. The expanded polyglutamine proteins influence a variety of cellular functions. In Drosophila the GMR-Gal4/UAS expression system has been widely used in an eye-based model to study human neurodegenerative diseases. This system has facilitated the isolation and characterization of abundant Drosophilagenes that interact with the expanded polyglutamine proteins. We used the GMR-Gal4/UAS system to express three proteins containing an expanded polyglutamine tract, or an expanded polyglutamine tract alone. Doubling the dose of these proteins resulted in pupal lethality, indicating that these toxic proteins induced a sensitized condition that is prone to synthetic lethality. By using the GMR-Gal4/UAS system, we showed that a Drosophilagene interacts with three expanded polyglutamine proteins to induce a synthetic lethal phenotype. We further demonstrated that the synthetic lethality was mediated through the toxic expanded polyglutamine tract. Our study raises a possibility that conventional genetic screens may not recover synthetic lethal alleles, which are presumably stronger interacting alleles than the currently known modifiers of an expanded polyglutamine tract, due to synthetic lethality.

Growth inhibition properties of the putative prostate cancer biomarkers PSP94 and CRISP-3

One of the major problems in prostate cancer （PCa） diagnosis and treatment relates to the difficulty in discriminating between slowgrowing, indolent cancers and more aggress- ive tumors with a lethal outcome. Therefore, much research has been devoted to the identification of reliable biomarkers that predict disease progression and treatment outcome.

迁移性树突状细胞与淋巴结内树突状细胞在抗B.suis免疫应答中的作用

目的:研究迁移性树突状细胞与淋巴结内树突状细胞在抗猪布鲁氏菌免疫应答中的作用。方法:48只BALB/c小鼠随机分为3组:Ⅰ组为正常对照组,阴道滴注PBS;Ⅱ组为巨噬细胞(Mφ)清除组,每只小鼠阴道滴入清除剂;Ⅲ组为未清除Mφ组,每只小鼠阴道滴注同体积的liposome-PBS;48小时后Ⅱ组、Ⅲ组均阴道接种猪布鲁氏菌,对照组阴道滴注PBS。各组小鼠分别在接种12、24、48和72小时采集血液和髂内淋巴结,采用免疫组织化学染色法观察淋巴结内树突状细胞(DC)的分布,用ELISA法检测血清中IFN-γ和IL-4的含量。结果:未清除Mφ组小鼠接种布鲁氏菌后髂内淋巴结内有大量DC迁移,至12小时血清IFN-γ水平显著增高,与对照组相比差异显著(P<0.05),48小时达到高峰,显著高于对照组(P<0.01)。清除Mφ组小鼠接种布鲁氏菌后,髂内淋巴结内没有明显的DC迁移,各时间点血清IFN-γ水平明显高于PBS对照组(P<0.05),但明显低于未清除Mφ组(P<0.05)。各组IL-4水平的差异无统计学意义(P>0.05)。结论:迁移性DC和淋巴结内DC在启动抗布鲁氏菌细胞免疫应答中均发挥重要作用,并具有协同作用的特点。

产前应激对发育海马神经元及其超微结构的影响

目的 :观察产前应激 (PS)对子鼠海马神经元和神经元超微结构是否有损伤作用 ,以及这种损伤是否与氧化物的过度生成有关。方法 :采用束缚应激模型 ,观察出生后 1个月雄性子鼠的海马神经元数量、神经元超微结构及神经型一氧化氮合酶 (nNOS)表达的变化。结果 :晚期应激 (LS)引起子鼠海马CA1和CA4区的细胞数量明显减少 ;电镜可见PS使子鼠海马CA1区神经元超微结构发生改变 ,表现为线粒体肿大、边界不清、电子密度不均 ,脂褐素增多 ,偶见核变形 ;中期应激 (MS)使子鼠海马CA1、CA2、CA3区和DG内nNOS阳性表达量显著升高 ,LS使子鼠海马CA1、CA2、CA3、CA4区和DG内nNOS阳性表达量也显著升高。结论 :结果提示 ,PS对子鼠海马神经元及神经元超微结构有损伤作用 ,这种损伤可能由氧化物过度生成引起。

Acute pancreatitis:The stress factor

Acute pancreatitis is an inflammatory disorder of the pancreas that may cause life-threatening complications.Etiologies of pancreatitis vary,with gallstones accounting for the majority of all cases,followed by alcohol.Other causes of pancreatitis include trauma,ischemia,mechanical obstruction,infections,autoimmune,hereditary,and drugs.The main events occurring in the pancreatic acinar cell that initiate and propagate acute pancreatitis include inhibition of secretion,intracellular activation of proteases,and generation of inflammatory mediators.Small cytokines known as chemokines are released from damaged pancreatic cells and attract inflammatory cells,whose systemic action ultimately determined the severity of the disease.Indeed,severe forms of pancreatitis may result in systemic inflammatory response syndrome and multiorgan dysfunction syndrome,characterized by a progressive physiologic failure of several interdependent organ systems.Stress occurs when homeostasis is threatened,and stressors can include physical or mental forces,or combinations of both.Depending on the timing and duration,stress can result in beneficial or harmful consequences.While it is well established that a previous acute-short-term stress decreases the severity of experimentally-induced pancreatitis,the worsening effects of chronic stress on the exocrine pancreas have received relatively little attention.This review will focus on the influence of both prior acute-short-term and chronic stress in acute pancreatitis.