左卡尼汀对糖尿病大鼠视网膜神经节细胞保护作用的实验研究

目的研究左卡尼汀对糖尿病大鼠视网膜神经节细胞的保护作用。方法通过STZ诱导建立I型糖尿病大鼠模型,成模后采用灌胃方式给予不同剂量的左卡尼汀口服液,6周后行电镜观察,比较疾病模型组与治疗组之间视网膜节细胞的超微结构变化,并进行DNA末端转移酶介导缺口末端标记(TUNEL)染色,观察细胞的凋亡情况。结果电镜显示药物治疗组神经节细胞核异染色质及线粒体空泡化较对照组减少,200 mg·kg-1的治疗剂量效果优于100 mg·kg-1组(P<0.05)。药物治疗组减少了由糖尿病导致的视网膜神经节细胞的凋亡数目(P<0.05)。结论左卡尼汀对糖尿病大鼠模型视网膜节细胞具有保护作用,抗凋亡可能是作用机制之一。

Anesthesia Management in Hereditary Pheochromocytoma and Paraganglioma:Updated Insights into Clinical Features and Perioperative Care

Approximately 40% of pheochromocytoma and paraganglioma(PPGL) cases are familial, typically presenting earlier with more complex symptoms. This paper synthesizes literature and guidelines to inform on clinical characteristics and perioperative care for PPGL. Pheochromocytoma in von Hippel-Lindau(VHL) disease exhibits heightened secretion activity without significant perioperative hemodynamic changes. Tumors in multiple endocrine neoplasia type 2(MEN2) have a stronger endocrine function, which may induce hemodynamic fluctuations during surgery. Therefore, pheochromocytoma screening is essential at all stages of MEN2. Neurofibromatosis type 1(NF1) often presents multisystem lesions and can result in difficult airway. Pheochromocytoma should be evaluated when NF1 patients present hypertension. Pheochromocytoma and paraganglioma type 5 may present multiple lesions of pheochromocytoma or paraganglioma. In summary, hereditary PPGLs may present with severe lesions in other systems, beyond tumor function. A multi-disciplinary team(MDT) approach is often invaluable in perioperative management.

Resection of the uncinate process of the pancreas due to a ganglioneuroma

A 33-year-old woman who presented with epigastric discomfort and diarrhea underwent an abdominal ultrasound(US).This investigation and subsequent contrastenhanced computed tomography,magnetic resonance imaging and endoscopic US with fine needle aspiration (FNA)revealed a 40 mm well-circumscribed mass in the uncinate process of the pancreas.Findings were suggestive of a mucinous or solid-cystic pseudopapillary tumor of the pancreas,although other lesions such as a nonfunctioning neuroendocrine tumor could not be ruled out.FNA samples were negative for malignant cells,but of limited value due to poor cellularity.It was decided to surgically remove the tumor because malignancy could not be discounted.Multiple intraoperative biopsies were suggestive of mesenchymal tumor and consequently a conservative resection(uncinatectomy)was performed. The postoperative course was uneventful.The definitive diagnosis was ganglioneuroma.Immunocytochemistry showed positive staining with vimentin,S-100 protein, neurofilament and neuron-specific enolase.Ganglioneuroma is a rare benign tumor that can also present as a pancreatic tumor.Uncinatectomy is feasible,safe and a good surgical technique for the treatment of nonmalignant tumors located in the uncinate process of the pancreas.

Hirschsprung's disease:Is there a relationship between mast cells and nerve fibers?

AIM:To define the topography of mast cells and their numbers in cases of Hirschsprung's disease(HD)and non-HD,assess neural hypertrophy using imaging software and to study the relationship between mast cells and nerve fibers.METHODS:HE stained sections of 32 cases of chronic constipation in the age group of 0-14 years were reviewed for ganglion cells.AChE staining was performed on frozen sections of colonic and rectal biopsies.Based on their findings cases were divided into HD and non-HD and mast cells stained by toluidine blue were evaluated.Image analysis by computerized software was applied to S-100 stained sections for assessment of neural hypertrophy.RESULTS:Difference between number of mast cells in HD group(mean=36.44)and in non-HD group(mean =14.79)was statistically significant.Image analysis morphometry on S-100 stained sections served as a useful adjunct.The difference between number,size,and perimeter of the nerve fibers between HD and non-HD group was statistically significant.CONCLUSION:Mast cells are significantly increased in HD and their base line values are much higher in Indian children than that reported in Western literature.Their role in HD needs further research.Morphometry of S-100 stained nerve fibers is a useful adjunct to conventional methods for diagnosis of HD.

Effects of Qingguang’an Granules on mitochondrial autophagy of retinal ganglion cells in rats with chronic ocular hypertension

Objective To investigate the effect and underlying mechanism of Qingguang’an Granules(青光安颗粒剂,QGAG)on mitochondrial autophagy(mitophagy)of retinal ganglion cells(RGCs)in rats with chronic ocular hypertension(COH).Methods Sixty Sprague Dawley(SD)rats,half males and half females,were randomly assigned to three groups:the control,model,and QGAG(2.5 g/kg)groups,with 20 rats in each group.Rats’model of COH was established by cauterizing episcleral veins in the model group and QGAG group.Three weeks after successful modeling,rats in the QGAG group were intra-gastrically administered with QGAG,while rats in the control group and the model group received an equal dose of normal saline.After three months of intragastric administration,intraocular pressure(IOP)of all rats was measured.The mitophagy was monitored by the immunofluorescence method,the mitochondrial membrane potential was measured using the JC-1 method,and the morphological changes of mitophagy in RGCs were observed by transmission electron microscopy.Meanwhile,rat RGCs were labeled using the fluorescent gold method,and RGCs density in each group was calculated.Moreover,RGCs apoptosis was observed by TdT-mediated dUTP Nick-End Labeling(TUNEL)assay.Finally,the expression levels of Parkin,optineurin,microtubule-associated protein 1 light chain 3-Ⅱ/microtubule-associated protein 1 light chain 3-Ⅰ(LC3-Ⅱ/LC3-Ⅰ),recombinant lysosomal associated membrane protein 1(LAMP1),and B-cell lymphoma-2(Bcl-2)in RGCs were determined by Western blot assay.The corresponding mRNAs were detected through quantitative real-time polymerase chain reaction(qRT-PCR).Results The QGAG reduced IOP in COH rats,and inhibited mitophagy and apoptosis of RGCs(P<0.05).Besides,the QGAG significantly increased the expression levels of Parkin and Bcl-2(P<0.05),and inhibited the expression levels of optineurin,LAMP1,and LC3-Ⅱ/LC3-Ⅰ(P<0.05)in RGCs of COH rats.Conclusion The QGAG can inhibit mitophagy in RGCs of COH rats and show a protective effect against optic nerve damage caused by glaucoma,which may be mediated through the mitophagy ubiquitination via the Parkin/PINK1-related pathway.

Proposal for a Reasonable Model of the Visual System： Principles of Clinical Neurosociology

This paper maintains that when photons enter the pupil and reach the Inner Limiting Membrane （ILM）, they are reflected onto a point or centroid of the vitreous body, which could be the lens, to be transmitted by the Muiller cells to the Retinal Pigment Epithelium （RPE） hexagonal cells, where an almost complete image is formed in each of them, overlapping with the adjacent images, to be carried subsequently by each of the ganglion cell axons to a place where the single image we are aware of is formed. This process calls for a high degree of control and coordination, which must be effected by the horizontal, amacrine, and interplexiform cells, gap junctions and the feedback provided from the V1 area to the Lateral Geniculate Nucleus （LGN）. But, as the ILM covers the optic disc but not the fovea, the latter must produce the blind spot and the rays reflected radially from the centroid must have the same centre as the Muller cells in order to be able to channel them to the RPE cells.

Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

Objective:To characterize the expression of aquaporin-4(AQP4),one of the aquaporins(AQPs),in human brainspecimens from patients with traumatic brain injury or brain tumors.Methods:Nineteen hnman brain specimens were obtahledfrom the patients with traumatic brain injury,brain tumors,benign meningioma or early stage hemorrhagic stroke.MRI or CTimaging was used to assess brain edema.Hematoxylin and eosm staining were used to evaluate cell damage,Immunohistochem-istry was used to detect the AQP4 expression.Results:AQP4 expression was increased from 15 h to at least 8 d after injury.AQP4immunoreactivity was strong around astrocytomas,ganglioglioma and metastatic adenocarcinoma.However,AQP4 immunore-activity was only found in the centers of astrocytomas and ganglioglioma,but not in metastatic adenocarcinoma derived from lung.Conclusion:AQP4 expression increases in human brains alter traumatic brain injury,within brain-derived tumors,and aroundbrain tumors.

PAd-shRNA-PTN reduces pleiotrophin of pancreatic cancer cells and inhibits neurite outgrowth of DRG

AIM:To investigate the silencing effects of pAdshRNA-pleiotrophin(PTN) on PTN in pancreatic cancer cells,and to observe the inhibition of pAd-shRNA-PTN on neurite outgrowth from dorsal root ganglion(DRG) neurons in vitro.METHODS:PAd-shRNA-PTN was used to infect pancreatic cancer BxPC-3 cells;assays were conducted for knockdown of the PTN gene on the 0th,1st,3rd,5th,7th and 9th d after infection using immunocytochemistry,real-time quantitative polymerase chain reaction(PCR),and Western blotting analysis.The morphologic changes of cultured DRG neurons were observed by mono-culture of DRG neurons and co-culture with BXPC-3 cells in vitro.RESULTS:The real-time quantitative PCR showed that the inhibition rates of PTN mRNA expression in the BxPC-3 cells were 20%,80%,50% and 25% on the 1st,3rd,5th and 7th d after infection.Immunocytochemistry and Western blotting analysis also revealed the same tendency.In contrast to the control,the DRG neurons co-cultured with the infected BxPC-3 cells shrunk;the number and length of neurites were significantly decreased.CONCLUSION:Efficient and specific knockdown of PTN in pancreatic cancer cells and the reduction in PTN expression resulted in the inhibition of neurite outgrowth from DRG neurons.

Gene expression profiling and endothelin in acute experimental pancreatitis

AIM:To analyze gene expression profiles in an experimental pancreatitis and provide functional reversal of hypersensitivity with candidate gene endothelin-1 antagonists.METHODS:Dibutyltin dichloride(DBTC) is a chemical used as a polyvinyl carbonate stabilizer/catalyzer,biocide in agriculture,antifouling agent in paint and fabric.DBTC induces an acute pancreatitis flare through generation of reactive oxygen species.Lewis-inbred rats received a single i.v.injection with either DBTC or vehicle.Spinal cord and dorsal root ganglia(DRG) were taken at the peak of inflammation and processed for transcriptional profiling with a cDNA microarray biased for rat brain-specific genes.In a second study,groups of animals with DBTC-induced pancreatitis were treated with endothelin(ET) receptor antagonists [ET-A(BQ123) and ET-B BQ788)].Spontaneous pain related mechanical and thermal hypersensitivity were measured.Immunohistochemical analysis was performed using anti-ET-A and ET-B antibodies on sections from pancreatic tissues and DRG of the T10-12 spinal segments.RESULTS:Animals developed acute pancreatic inflammation persisting 7-10 d as confirmed by pathological studies(edema in parenchyma,loss of pancreatic architecture and islets,infiltration of inflammatory cells,neutrophil and mononuclear cells,degeneration,vacuolization and necrosis of acinar cells) and the painrelated behaviors(cutaneous secondary mechanical and thermal hypersensitivity).Gene expression profile was different in the spinal cord from animals with pancreatitis compared to the vehicle control group.Over 260 up-regulated and 60 down-regulated unique genes could be classified into 8 functional gene families:circulatory/acute phase/immunomodulatory;extracellular matrix;structural;channel/receptor/transporter;signaling transduction;transcription/translation-related;antioxidants/chaperones/heat shock;pancreatic and other enzymes.ET-1 was among the 52 candidate genes upregulated greater than 2-fold in animals with pancreatic inflammation and visceral pain-related behavior.Treatments with the ET-A(BQ123) and ET-B(BQ-788) antagonists revealed significant protection against inflammatory pain related mechanical and thermal hypersensitivity behaviors in animals with pancreatitis(P < 0.05).Open field spontaneous behavioral activity(at baseline,day 6 and 30 min after drug treatments(BQ123,BQ788) showed overall stable activity levels indicating that the drugs produced no undesirable effects on normal exploratory behaviors,except for a trend toward reduction of the active time and increase in resting time at the highest dose(300 μmol/L).Immunocytochemical localization revealed that expression of ET-A and ET-B receptors increased in DRG from animals with pancreatitis.Endothelin receptor localization was combined in dual staining with neuronal marker NeuN,and glia marker,glial fibrillary acidic protein.ET-A was expressed in the cell bodies and occasional nuclei of DRG neurons in na ve animals.However,phenotypic expression of ET-A receptor was greatly increased in neurons of all sizes in animals with pancreatitis.Similarly,ET-B receptor was localized in neurons and in the satellite glia,as well as in the Schwann cell glial myelin sheaths surrounding the axons passing through the DRG.CONCLUSION:Endothelin-receptor antagonists protect against inflammatory pain responses without interfering with normal exploratory behaviors.Candidate genes can serve as future biomarkers for diagnosis and/or targeted gene therapy.

Retinal ganglion cells of high cytochrome oxidase activity in the rat

Retinal ganglion cells in the rat were studied using the heavy metal intensified oytochrome oxidase and horseradish peroxidase histochemieal methods. The results show that a population of large retinal ganglion cells was consistently observed with the eyto3hrome oxidase staining method in retinas of normal rats or rats which received unilateral thalamotomy at birrth. These oytochrome oxidase rich ganglion cells appeared to have large somata, 3-6 primary dendrites and extensive dendritic arbors, and are comparable to ganglion cells labeled by the wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). However, the morphological details of some of the cells revealed by the cytoahrome oxidase staining method are frequently better than those shown by the HRP histochemieal method. These results suggest that the mit03hondrial enzyme oytoohrome oxidase can be used as a simple but reliable marker for identifying and studying a population of retinal ganglion cells with high metabolie rate in the rat.

Role of nuclear receptor NR4A2 in gastrointestinal inflammation and cancers

NR4A2 is a transcription factor belonging to the steroid orphan nuclear receptor superfamily.It was originally considered to be essential in the generation and maintenance of dopaminergic neurons,and associated with neurological disorders such as Parkinson's disease.Recently,NR4A2 has been found to play a critical role in some inflammatory diseases and cancer.NR4A2 can be efficiently trans-activated by some proinflammatory cytokines,such as tumor necrosis factor-α,interleukin-1β,and vascular endothelial growth factor(VEGF).The nuclear factor-κB signaling pathway serves as a principal regulator of inducible NR4A expression in immune cells.NR4A2 can trans-activate Foxp3,a hallmark specifically expressed in regulatory T(Treg) cells,and plays a critical role in the differentiation,maintenance,and function of Treg cells.NR4A2 in T lymphocytes is pivotal for Treg cell induction and suppression of aberrant induction of Th1 under physiological and pathological conditions.High density of Foxp3 + Treg cells is significantly associated with gastrointestinal inflammation,tumor immune escape,and disease progression.NR4A2 is produced at high levels in CD133 + colorectal carcinoma(CRC) cells and significantly upregulated by cyclooxygenase-2-derived prostaglandin E 2 in a cyclic adenosine monophosphate(cAMP)/protein kinase A(PKA)-dependent manner in CRC cells.The cAMP/PKA signaling pathway is the common pathway of NR4A2-related inflammation and cancer.NR4A2 trans-activates osteopontin,a direct target of the Wnt/β-catenin pathway associated with CRC invasion,metastasis,and poor prognosis.Knockdown of endogenous NR4A2 expression attenuates VEGF-induced endothelial cell proliferation,migration and in vivo angiogenesis.Taken together,NR4A2 emerges as an important nuclear factor linking gastrointestinal inflammation and cancer,especially CRC,and should serve as a candidate therapeutic target for inflammation-related gastrointestinal cancer.

Pro-protein convertase-2/carboxypeptidase-E mediated neuropeptide processing of RGC-5 cell after in vitro ischemia

Objective To observe the change of the neuropeptide pro-protein processing system in the ischemic retina ganglion cell-5(RGC-5) cells,pro-protein convertase-2(PC2),carboxypeptidase-E(CPE) and preproneuropeptide Y(preproNPY) protein levels in the ischemic RGC-5 cells and conditioned medium were analyzed. Methods The RGC-5 cell was differentiated in 0.1 μmol/L staurosporine for 24 h and then stressed by different doses of oxygen and glucose deprivation(OGD). The acute or chronic OGD-induced cell death rates w...

Association between retinal neuronal degeneration and visual function impairment in type 2 diabetic patients without diabetic retinopathy

The changes in retinal thickness and visual function in type 2 diabetic patients without clinical evidence of diabetic retinopathy were evaluated. A total of 141 diabetic subjects without retinopathy and 158 healthy subjects were enrolled in this study. Superior macular ganglion cell complex thicknesses were significantly decreased in diabetic cases, and no significant peripapillary retinal nerve fiber layer thickness changes were observed. The contrast sensitivities at all space frequencies were significantly different between diabetic patients and controls. The mean P50 amplitude from pattern electroretinogram results was reduced significantly in the diabetic group. In the diabetic group, average superior ganglion cell complex thicknesses positively correlated with both contrast sensitivities at high spatial frequencies and P50 amplitudes. The results indicated that ganglion cell complex thickness and visual function changes could be observed in diabetic subjects before the onset of any significant diabetic retinopathy. Macular ganglion cell complex reduction occurred much earlier than peripapillary retinal nerve fiber layer thinning in diabetic patients without retinopathy.

Epac2-deficiency leads to more severe retinal swelling, glial reactivity and oxidative stress in transient middle cerebral artery occlusion induced ischemic retinopathy

Ischemia occurs in diabetic retinopathy with neuronal loss, edema, glial cell reactivity and oxidative stress. Epacs, consisting of Epac 1 and Epac2, are cAMP mediators playing important roles in maintenance of endothelial barrier and neuronal functions To investigate the roles of Epacs in the pathogenesis of ischemic retinopathy, transient middle cerebral artery occlusion （tMCAO） was performed on Epacl-deficient （Epacl-/- ） mice, Epac2-deficient （Epac2-/-） mice, and their wild type counter-parts （Epacl＋/＋ and Epac2＋/＋）. Two-hour occlusion and 22-hour reperfusion were conducted to induce ischemia/reperfusion injury to the retina. After tMCAO, the contralateral retinae displayed similar morphology between different genotypes. Neu-ronal loss, retinal edema and increase in immunoreactivity for aquaporin 4 （AQP4）, glial fibrillary acidic protein （GFAP）, peroxiredoxin 6 （Prx6） were observed in ipsilateral retinae. Epac2 / ipsilateral retinae showed more neuronal loss in retinal ganglion cell layer, increased retinal thickness and stronger immunostaining of AQP4, GFAP, and Prx6 than those of Epac2＋/＋. However, Epacl-/- ipsilateral retinae displayed similar pathology as those in Epacl＋/＋ mice. Our observations suggest that Epac2-deficiency led to more severe ischemic retinopathy after retinal ischemia/reperfusion injury.

microRNA-21a-5p/PDCD4 axis regulates mesenchymal stem cell-induced neuroprotection in acute glaucoma

Mesenchymal stem ceils （MSCs） have been demonstrated to have promising therapeutic benefits for a variety of neurological dis- eases; however, the underlying mechanisms are poorly understood. Here, we showed that intravitreal infusion of MSCs promoted retinal ganglion cell （RGC） survival in a mouse model of acute glaucoma, with significant inhibition of microglial activation, production of TNF-α, IL-1β, and reactive oxygen species, as well as caspase-8 and caspase-3 activation. In vitro, MSCs inhibited both caspase-8-mediated RGC apoptosis and microgUal activation, partly via the action of stanniocalcin 1 （STCl）. Furthermore, we found that microRNA-21a-Sp （miR-21） and its target, PDCD4, were essential for STC1 production and the neuroprotective property of MSCs in vitro and in vivo. Importantly, miR-21 overexpression or PDCD4 knockdown augmented MSC-mediated neuroprotective effects on acute glaucoma. These data highlight a previously unrecognized neuroprotective mechanism by which the miR-21/ PDCD4 axis induces MSCs to secrete STC1 and other factors that exert neuroprotective effects. Therefore, modulating the miR- 21/PDCD4 axis might be a promising strategy for clinical treatment of acute glaucoma and other neurological diseases.

Melanopsin-expressing retinal ganglion cell loss and behavioral analysis in the Thy1-CFP-DBA/2J mouse model of glaucoma

In this study, the role of melanopsin-expressing retinal ganglion cells （mRGCs） in the glaucoma-induced depressive behavioral response pattern was investigated. The CFP-D2 transgenic glaucoma animal model from five age groups was used in this study. Immunohistochemical labeling, quantitative analysis of mRGC morphology, open field test （OFT）, and statistical analysis were used. In comparison with C57 BL/6 mice, the age-matched CFP-D2 mice had significantly elevated intraocular pressure （lOP）. We observed parallel morphological changes in the retina, including a reduction in the density of cyan fluorescent protein- （CFP） expressing cells （cells mm^-2 at 2 months of age, 1309±26; 14 months, 878±30, P〈0.001）, mRGCs （2 months, 48_＋3; 14 months, 19±4, P〈0.001）, Brn3b-expressing RGCs （2 months, 1283±80; 14 months, 950±31, P〈0.001）, Brn-3b expressing mRGCs （5 months, 50.17%±5.5%; 14 months, 12.61%±3.8%, P〈0.001）, and reduction in the dendritic field size of mRGCs （mm^2 at 2 months, 0.077±0.015; 14 months, 0.065±0.015, P〈0.05）. CFP-D2 mice had hyperactive locomotor activity patterns based on OFT findings of the total distance traveled, number of entries into the center, and time spent in the center of the testing apparatus. The glaucoma induced hyperactive response pattern could be associated with dysfunctional mRGCs, most likely Brn-3b-positive mRGCs in CFP-D2 mice.

Comparison of laparoscopic selective colectomy based on barium-strip examination and subtotal colectomy for adult slow-transit constipation

Background:Surgical management of adult slow-transit constipation(ASTC)can be effective for patients with intractable symptoms.This study aimed to evaluate whether barium-strip examination and selective colectomy improved post-operative outcomes in ASTC patients in comparison with subtotal colectomy.Methods:A retrospective cohort study of 53 cases with refractory ASTC was conducted between June 2008 and June 2014.Patients were evaluated by the barium-strip technique,colonoscopy,defecography and anorectal manometry.Patients in the standard group underwent laparoscopic subtotal colectomy and patients in the laparoscopic selective colectomy(LSC)group underwent LSC at the precise location identified by barium strip.Spontaneous bowel movements,the Wexner Constipation Scale and the Gastrointestinal Quality of Life Index(GIQLI)were assessed post-operatively at 3,6,12 and 24 months.Results:A total of 49 patients were included in the analysis.The median follow-up was 37 months(range,26–60 months).The mean post-operative hospital stay was 12 days and similar between groups(P=0.071).The length of colon resection,operative time and intra-operative blood loss were reduced in the LSC group(all P<0.05).No major complications occurred.A similar number of patients(24 in the standard group and 25 in the LSC group)exhibited hypoganglionosis or aganglionosis in the colon-wall muscle layer(P=0.986).Although there were no significant differences in post-operative spontaneous bowel movements and the Wexner Constipation Scale between the two groups,the mean GIQLI of the LSC group was significantly higher at 3,6 and 24 months post-operatively(all P<0.05).Conclusions:LSC based on barium-strip examination is an appropriate modality for treating ASTC.

Human cytomegalovirus infection dysregulates neural progenitor cell fate by disrupting Hes1 rhythm and down-regulating its expression

Human cytomegalovirus(HCMV) infection is a leading cause of birth defects, primarily affecting the central nervous system and causing its maldevelopment. As the essential downstream effector of Notch signaling pathway, Hes1, and its dynamic expression, plays an essential role on maintaining neural progenitor/stem cells(NPCs) cell fate and fetal brain development. In the present study, we reported the first observation of Hes1 oscillatory expression in human NPCs, with an approximately1.5 hour periodicity and a Hes1 protein half-life of about 17(17.6 ± 0.2) minutes. HCMV infection disrupts the Hes1 rhythm and down-regulates its expression. Furthermore, we discovered that depleting Hes1 protein disturbed NPCs cell fate by suppressing NPCs proliferation and neurosphere formation, and driving NPCs abnormal differentiation. These results suggested a novel mechanism linking disruption of Hes1 rhythm and down-regulation of Hes1 expression to neurodevelopmental disorders caused by congenital HCMV infection.

Increased susceptibility of algal symbionts to photo-inhibition resulting from the perturbation of coral gastrodermal membrane trafficking

The stability of cnidarian-dinoflagellate endosymbioses is dependent upon communication between the host gastrodermal cell and the symbionts housed within it. Although the molecular mechanisms remain to be elucidated, existing evidence suggests that the establishment of these endosymbioses may involve the sorting of membrane proteins. The present study examined the role of host gastrodermal membranes in regulating symbiont （genus Symbiodinium） photosynthesis in the stony coral Euphyllia glabrescens. In comparison with the photosynthetic behavior of Symbiodinium in culture, the Symbiodinium populations within isolated symbiotic gastrodermal cells （SGCs） exhibited a significant degree of photo-inhibition, as determined by a decrease in the photochemical efficiency of photosystem II （Fv/Fm）. This photo-inhibition coincided with increases in plasma membrane perturbation and oxidative activity in the SGCs. Membrane trafficking in SGCs was examined using the metabolism of a fluo- rescent lipid analog, N-[5-（5,7-dimethyl boron dipyrromethene difluoride）-l-pentanoyl]-D-erythro-Sphingosylpbosphoryl- choline （BODIPY-Sphingomyelin or BODIPY-SM）. Light irradiation altered both membrane distribution and trafficking of BODIPY-SM, resulting in metabolic changes. Cholesterol depletion of the SGC plasma membranes by methyl-13-cyclodextrin retarded BODIPY-SM degradation and further augmented Symbiodinium photo-inhibition. These results indicate that Symbio- dinium photo-inhibition may be related to perturbation of the host gastrodermal membrane, providing evidence for the pivotal role of host membrane trafficking in the regulation of this environmentally important coral-dinoflagellate endosymbiosis.

Recombinant human erythropoietin counteracts cisplatin-induced visceral hyperalgesia

Objective Cisplatin exerts its cytotoxic effect through distinct DNA lesions,leading to peripheral neuropathy.The risk of sensory neuropathy is a common problem during cancer treatment with cisplatin,leading to somatic hyperalgesia.Yet,data focussing on cisplatin-induced impairment of the autonomic nervous system are limited.The present study was aimed to investigate the effect of recombinant human erythropoietin（rhEPO）on cisplatin-induced visceral hyperalgesia.Methods C57BL/6 mice were treated either with cisplatin（2 mg/kg,once per week）or with cisplatin（2 mg/kg,once per week）plus rhEPO （40μg/kg,3 times per week）for 8 weeks.Controls were treated with saline.To quantify the visceromotor response（VMR）at week 9,standardized electrodes were implanted into the external oblique musculature for electromyographic recordings.After that,animals were decapitated and dorsal root ganglia（DRG）was removed for transmission electron microscopy studies.Results Cisplatin-treated mice showed a significant increase of VMR compared to the controls[（7080±969）vs（2864±279）;P0.001],while rhEPO dramatically counteracted this effect[（2962±336）vs（7080±969）;P0.001）].Transmission electron microscopy revealed cisplatin-induced structural lesions of nuclear membrane in DRG cells,which could be ameliorated by rhEPO.Conclusion Erythropoietin can significantly ameliorate the cisplatin-induced visceral hyperplasia and DRG nuclear membrane structure damage in mice,indicating a neuroprotective role of erythropoietin.