Glaucoma is characterized by chronic progressive optic nerve damage and retinal ganglion cell death.Although extensive research has been conducted on neuroprotection for retinal ganglion cells,there is still no treatm...Glaucoma is characterized by chronic progressive optic nerve damage and retinal ganglion cell death.Although extensive research has been conducted on neuroprotection for retinal ganglion cells,there is still no treatment for clinical use.Recent evidence shows that extracellular vesicles isolated from a variety of stem cells are efficacious in retinal ganglion cell neuroprotection.In this study,we tested the novel extracellular vesicle source of the retinal progenitor R-28 cell line in vitro and in vivo.We isolated and characterized extracellular vesicles from R-28 cells and tested their therapeutic efficacy in terms of retinal ganglion cell survival in vitro and in an in vivo glaucoma model,measuring retinal ganglion cell survival and preservation of their axons.Additionally,we tested extracellular vesicles for their neuroprotective capacity in retinal ganglion cells differentiated from human embryonic stem cells.Finally,we investigated miRNA changes in retinal ganglion cells with R-28 extracellular vesicle treatment,and predicted possible pathways that may be modulated.R-28 extracellular vesicles improved retinal ganglion cell survival but failed to preserve axons significantly.Moreover,the results also illustrated the neuroprotection of R-28 extracellular vesicles on human retinal ganglion cells.Finally,we also showed changes in hsa-miRNA-4443,hsa-miRNA-216a-5p,hsa-let-7e-5p,hsa-miRNA-374b-5p,hsa-miRNA-331-3p,and hsa-miRNA-421 expressions,which may have neuroprotective potential on retinal ganglion cell degeneration.This study will pave the way for miRNA and extracellular vesicle-based neuroprotective therapies for glaucoma.展开更多
Calcium (Ca^(2+)) is a key intracellular messenger involved in a variety of cellular functions.Intracellular Ca^(2+)dysregulation drives neuron cell death in multiple degenerative diseases and traumatic conditions.Ret...Calcium (Ca^(2+)) is a key intracellular messenger involved in a variety of cellular functions.Intracellular Ca^(2+)dysregulation drives neuron cell death in multiple degenerative diseases and traumatic conditions.Retinal ganglion cell(RGC) degeneration occurs in blinding diseases such as glaucoma and other optic neuropathies.展开更多
Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial spectrum.However,their use leads to irreversible hearing damage by causing apoptosis of hair cells as ...Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial spectrum.However,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct target.In addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon exposure.To investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with kanamycin.We found that the mice exhibited auditory deficits following the acute loss of outer hair cells.Spiral ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over time.Transcriptomic profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 inflammasome.Activation of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory cytokines.Pharmacological intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury model.These findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron degeneration.Inhibition of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.展开更多
Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limit...Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.展开更多
Salidroside(Sal),is one of the important food supplements from the traditional Chinese medicine Integripetal rhodiola herb,encapsulating significant anti-oxidative stress,anti-ferroptosis,and neuroprotective attribute...Salidroside(Sal),is one of the important food supplements from the traditional Chinese medicine Integripetal rhodiola herb,encapsulating significant anti-oxidative stress,anti-ferroptosis,and neuroprotective attributes.Notwithstanding these latent virtues,the ramifications of Sal on retinal ganglion cells(RGCs)impairment during the incipient stages of diabetic retinopathy(DR)remain equivocal.The purpose of this study was to investigate inhibitory effect of Sal on ferroptosis of RGCs in db/db mice.Within the research conducted,Sal was administered via gavage,and observations were made 8 weeks post-treatment.Retinal samples were collected for analysis.The results evidenced that Sal ameliorated blood glucose levels,attenuated RGCs destruction,and augmented visual functionality in db/db mice.Additionally,Sal exerted an anti-ferroptosis impact on the RGCs in the db/db mice.Successive discoveries have outlined the involvement of the HIF-1α/HO-1 signaling pathway in this protective mechanism.Ferroptosis of RGCs has a contributory effect on the development of DR,in part through the HIF-1α/HO-1 pathway.Intriguingly,Sal reversed the alterations in the HIF-1α/HO-1 pathway in db/db mice and displayed prospective advantageous effects on DR.Sal mitigated RGCs ferroptosis by reducing blood sugar and impeding the HIF-1α/HO-1 signaling pathway,thereby improving DR.Thus,Sal shows potential for use as a pharmaceutical and nutraceutical for DR.展开更多
Glaucoma is a group of diseases characterized by progressive optic nerve degeneration,with the characteristic pathological change being death of retinal ganglion cells(RGCs),which ultimately causes visual field loss a...Glaucoma is a group of diseases characterized by progressive optic nerve degeneration,with the characteristic pathological change being death of retinal ganglion cells(RGCs),which ultimately causes visual field loss and irreversible blindness.Elevated intraocular pressure(IOP)remains the most important risk factor for glaucoma,but the exact mechanism responsible for the death of RGCs is currently unknown.Neurotrophic factor deficiency,impaired mitochondrial structure and function,disrupted axonal transport,disturbed Ca2+homeostasis,and activation of apoptotic and autophagic pathways play important roles in RGC death in glaucoma.This review was conducted using Web of Science,PubMed,Project,and other databases to summarize the relevant mechanisms of death of RGCs in glaucoma,in addition to outlining protective treatments to improve the degradation of RGCs.展开更多
AIM:To explore the neuroprotective effects of high mobility group box 2(HMGB2)knockdown on retinal ganglion cells(RGCs)in the retinal ischemia-reperfusion injury(RIRI).METHODS:Oxygen-glucose deprivation(OGD)-injured R...AIM:To explore the neuroprotective effects of high mobility group box 2(HMGB2)knockdown on retinal ganglion cells(RGCs)in the retinal ischemia-reperfusion injury(RIRI).METHODS:Oxygen-glucose deprivation(OGD)-injured RGCs from postnatal three-day C57BL/6 mice pups and high intraocular pressure(IOP)-induced RIRI mice were used as cellular and animal models of RIRI.The expression of HMGB2 in the retina of RIRI mice and OGD-injured RGCs was detected through reverse transcription-polymerase chain reaction(RT-qPCR)and Western blotting.The effects of HMGB2 silencing on the morphological changes,RGCs survival,and cell apoptosis in mouse retinal tissues were observed through H&E staining,immunofluorescence staining with RNA-binding protein with multiple splicing(RBPMS)antibody,and TUNEL staining,respectively.RGC viability and apoptosis were examined by CCK-8 and flow cytometry assays.The levels of proteins associated with NOD-like receptor thermal protein domain associated protein 3(NLRP3)-mediated pyroptosis[NLRP3,Caspase-1,GSDMD-N,interleukin(IL)-1β,IL-18]in vivo and in vitro were measured by Western blotting.RESULTS:HMGB2 protein and NLRP3 were upregulated in the retina of RIRI mice and OGD-injured RGCs(P<0.001).The retina was edematous,accompanied by disorganized cell arrangement and decreased thickness of all layers,and obvious vacuoles in ganglion cell layer.HMGB2 silencing alleviated the reduction in total retinal thickness and the severity of retinal tissue damage as well as suppressed RGC loss and retinal cell apoptosis in RIRI mice.OGD-induced RGC apoptosis was ameliorated after downregulation of HMGB2 in vitro.Intravitreal injection of the AAV-sh-HMGB2 and si-HMGB2 resulted in significantly decrease of NLRP3,Caspase-1,GSDMD-N,IL-1β,and IL-18 protein levels in the retinal tissues of RIRI mice and OGD-injured RGCs,respectively(all P<0.001).CONCLUSION:HMGB2 knockdown protects against RGC apoptosis and pyroptosis after RIRI through suppressing NLRP3 inflammasome activation.展开更多
BACKGROUND Surgery is a common treatment for gastrointestinal tumors.General anesthesia(GA),while effective,can cause oxidative stress reactions and neuroinflammation,potentially leading to postoperative cognitive dys...BACKGROUND Surgery is a common treatment for gastrointestinal tumors.General anesthesia(GA),while effective,can cause oxidative stress reactions and neuroinflammation,potentially leading to postoperative cognitive dysfunction and gastrointestinal dysfunction.The stellate ganglion block(SGB)can reduce sympathetic excitability and stress responses.This study aims to investigate whether combining SGB with GA can mitigate these adverse effects in patients undergoing gastrointestinal surgery.AIM To analyze the effects of SGB plus GA on hemodynamic stability,oxidative stress,neuroinflammation,cognitive function,and gastrointestinal function in patients undergoing gastrointestinal surgery.METHODS Patients undergoing gastrointestinal surgery between October 2022 and December 2024 were divided into two groups:A single GA group and an SGB combined with GA group(40 patients each).Hemodynamics,oxidative stress response,laboratory indices,cognitive function,and gastrointestinal function were compared preoperatively and 24 hours postoperatively between the two groups.Pain levels and complications were also recorded.RESULTS Before anesthesia induction,no significant differences were found in various indexes(including hemodynamics,oxidative stress indicators,laboratory indices,cognitive function scores,and gastrointestinal function indicators)between the two groups(P>0.05).At tracheal intubation,3 minutes after,and extubation,the GA-only group had significantly higher mean arterial pressure and heart rate postoperatively than preoperatively and compared to the SGB-GA combined group(P<0.05).Twentyfour hours postoperatively,oxidative stress indicators(malondialdehyde and nitric oxide)were significantly higher and superoxide dismutase was significantly lower in the GA group than in the SGB-GA combined group(P<0.05).Cognitive function scores[Mini-Mental State Examination and Montreal Cognitive Assessment(MoCA)]and gastrointestinal function indicators(motilin)were also significantly better in the SGB-GA combined group(P<0.05).The 24-hour postoperative MoCA score was 0.98 points higher in the SGB-GA combined group.No significant differences were found in the time of first postoperative ambulation,catheter removal time,and 24-hour postoperative pain between groups(P>0.05).CONCLUSION Combining SGB with GA can maintain perioperative hemodynamic stability,reduce oxidative stress and neuroinflammatory injury,and attenuate postoperative cognitive decline and gastrointestinal dysfunction in patients undergoing gastrointestinal surgery.展开更多
BACKGROUND Anterior visual pathway lesions can cause severe visual loss.Optical coherence tomography(OCT)can detect ganglion cell complex(GCC)thinning,even with normal retinal nerve fiber layer(RNFL)thickness and subt...BACKGROUND Anterior visual pathway lesions can cause severe visual loss.Optical coherence tomography(OCT)can detect ganglion cell complex(GCC)thinning,even with normal retinal nerve fiber layer(RNFL)thickness and subtle visual field changes.AIM To determine the proportion of eyes with RNFL and GCC thinning and their association with visual parameters in patients with brain tumors undergoing surgery.METHODS A prospective study was conducted on 37 patients(69 eyes)with peri-chiasmatic and chiasmatic brain tumors undergoing surgical decompression between February 2019 and June 2020 at a tertiary care institute.A comprehensive neuroophthalmological work-up,demographic and clinical profile documentation,and six-month postoperative follow-up weredone.Statistical analysis was significant at P<0.05.RESULTS Mean age was 35.14±11.98 years.The best and worst visual outcomes were associated with the craniopharyngioma and meningioma groups,respectively(P=0.008).There was an increase in the proportion of eyes with RNFL damage in the inferior quadrant(P=0.02).Maximum GCC thickness thinning was associated with severe visual impairment.The odds of having blindness in eyes with RNFL(inferior)and GCC loss were 0.96(P=0.003)and 0.95(P=0.03),respectively.GCC thickness showed a clinically positive correlation with visual acuity(r=-0.48,P<0.001)and field defect(r=-0.27,P=0.04)at six months postoperatively.The preoperative GCC thickness and the final postoperative visual outcome were plotted in an empirical ROC curve with area under the curve=0.754.The cut-off value of RNFL(inferior)and GCC,beyond which blindness could be prevented,was 73μm and 58μm,respectively.CONCLUSION In chiasmal compression,RNFL and GCC thickness measurements using OCT can be a useful prognostic indicator for assessing visual recovery.An eye with structural damage,with significant RNFL and GCC loss,is a predictive factor of blindness.A minimum preoperative RNFL and GCC thickness of 73μm and 58μm,respectively,can preserve vision after surgery.展开更多
AIM:To explore the impact of insulin-like growth factor-1 receptorα(IGF-1Rα)on the differentiation fate of optic-cupderived retinal stem cells(OC-RSCs)into retinal ganglion cells(RGCs)in vitro.METHODS:OC-RSCs were i...AIM:To explore the impact of insulin-like growth factor-1 receptorα(IGF-1Rα)on the differentiation fate of optic-cupderived retinal stem cells(OC-RSCs)into retinal ganglion cells(RGCs)in vitro.METHODS:OC-RSCs were isolated from optic cups of rats on embryonic day 12.5,and high-purity OC-RSCs were obtained by conditioned culture and passage.Differentiation of OC-RSCs into RGCs under different serum concentrations was examined using flow cytometry,and the serum concentration with high interference with differentiation ratio was selected.Furthermore,the effect of blocking IGF-1Rαon the differentiation of OC-RSCs into RGCs was analyzed through immunocytochemistry and Western blotting.RESULTS:Immunohistochemical analysis revealed IGF-1Rαwas highly expressed in rat embryos at day 12.5.OC-RSCs were isolated and purified,and high-purity OCRSCs were obtained.When 2.5%serum was administered,the ratio of differentiated RGCs(Thy-1.1 positive)decreased significantly,and the results of immunoblotting also confirmed the blockade of IGF-1Rαreduced Thy-1.1 protein expression.CONCLUSION:IGF-1Rαblocking can reduce the differentiation of OC-RSCs into RGCs.展开更多
Immunoreactivity (IR) for vasoactive intestinal polypeptide (VIP) of cranial parasympathetic ganglia of the rat was observed with indirect immunofluorescent method. It was found that there were VIP IR principal neuro...Immunoreactivity (IR) for vasoactive intestinal polypeptide (VIP) of cranial parasympathetic ganglia of the rat was observed with indirect immunofluorescent method. It was found that there were VIP IR principal neurons in the ciliary, pterygopalatine, and otic ganglia. The highest positive ratio of VIP IR cells was located in the ciliary ganglia (34.8%), followed by that in the pterygopalatine ganglia(17.0%), and the lowest was found in the otic ganglia (15.4%). VIP IR small intensely fluorescent (SIF) cells and nerve fibers were not observed. Distributive characteristics of neuropeptides and functional significance of VIP in cranial parasympathetic ganglia were discussed.展开更多
The development, cytological characters and ultrastructure of phloem ganglion in the nodal region of Phyllostachys edulis (Carr.) H. de Lehaie, a most economically important bamboo, were investigated and the possi...The development, cytological characters and ultrastructure of phloem ganglion in the nodal region of Phyllostachys edulis (Carr.) H. de Lehaie, a most economically important bamboo, were investigated and the possible physiological function of this special structure was proposed. The phloem ganglion derived directly from procambium is situated at the sites where the vascular bundle forks and is present in pairs. The phloem ganglion is spindle_like in appearance and usually consists of 4 to 6 layers. Two kinds of cells in the ganglion could be distinguished. In the middle, there are two layers of filiform cells with pointed ends so that there are no normal sieve plates. Nevertheless, there are many pits on the lateral wall of the filiform cells. The other type of cells located at both ends of the spindle which possess an intermediate form between the filiform cell and the normal sieve tube. The walls of these cells towards the filiform cells are strongly convex forming a special sieve plate. Ultrastructure study showed that cells in the ganglion are connected by enriched plasmodesma. During early differentiation, the paramural body and the ingrowth of cell wall could be observed. It indicates that the cells of phloem ganglion have the character of transfer cells. The organelles in the mature cells are mainly plastids with abundant accumulation of proteins of crystalline structure. The above_mentioned results suggest that the physiological function of the phloem ganglion is closely related with substance transport.展开更多
Objective To explore the best therapeutic method in the treatment of peripheral facial paralysis. Methods One hundred and twenty cases were randomized into a conventional acupuncture group [Yangbai （阳白 GB 24）, Sib...Objective To explore the best therapeutic method in the treatment of peripheral facial paralysis. Methods One hundred and twenty cases were randomized into a conventional acupuncture group [Yangbai （阳白 GB 24）, Sibai （四白 ST 2）, Yingxiang （迎香 LI 20）, etc.], a Renying （人迎ST 9） acupuncture group and an operation ＋ acupuncture group [acupuncture at ST 9 as the main acupoint and the stellate ganglion block （SGB）], 40 cases in each one. The treatment was given once a day, 7 treatments made one session. After 3 sessions of treatment, the latency and the amplitude of the direct stimulation evoked potential of the facial nerve （ENoG） were compared before and after treatment in three groups, as well as R2 and R2 values of blink reflex （BR）. The total clinical efficacy was assessed. Results The latency of ENoG was shortened and the amplitude was increased significantly in three groups. After treatment, ENoG latency was lower significantly in the operation ＋ acupuncture group as compared with that in the conventional acupuncture group （P〈0.05）. In the Renying （人迎 ST 9） acupuncture group, the amplitude of ENoG was increased as compared with P〈0.05）. After treatment in three groups, those in the other two groups （all R2 and R2 values were decreased significantly. The differences in R1 and R2 values in the Renying （人迎 ST 9） acupuncture group and the operation ＋ acupuncture group before and after treatment were bigger than those in the conventional acupuncture group （all P〈0.05）, and the difference in R2 value in the operation ＋ acupuncture group was bigger than that in the Renying （人迎 ST 9） acupuncture group （P〈O.05）. The clinical markedly effective and curative rate was 87.5% （35/40） in the operation ＋ acupuncture group, which was superior to 77.5% （32/40） in the Renying （）人迎 ST 9）acupuncture group and higher significantly than 65.0% （26/40） in the conventional acupuncture group （P〈0.05）. Conclusion Compared with the conventional acupuncture, the efficacy on peripheral facial paralysis is much better in the Renying （人迎 ST 9） acupuncture group and the operation ＋ acupuncture group. Moreover, the early reflex function of the damaged facial nerve is much better recovered in the operation ＋ acupuncture group as compared with that in the Renying （人迎 ST 9） acupuncture group.展开更多
Pituitary adenylate cyclase-activating polypeptide（PACAP） is an endogenous peptide with neuroprotective effects on retinal neurons, but the precise mechanism underlying these effects remains unknown. Considering the...Pituitary adenylate cyclase-activating polypeptide（PACAP） is an endogenous peptide with neuroprotective effects on retinal neurons, but the precise mechanism underlying these effects remains unknown. Considering the abundance of mitochondria in retinal ganglion cells（RGCs）, we postulate that the protective effect of PACAP is associated with the regulation of mitochondrial function. RGC-5 cells were subjected to serum deprivation for 48 hours to induce apoptosis in the presence or absence of 100 nM PACAP. As revealed with the Cell Counting Kit-8 assay, PACAP at different concentrations significantly increased the viability of RGC-5 cells. PACAP also inhibited the excessive generation of reactive oxygen species in RGC-5 cells subjected to serum deprivation. We also showed by flow cytometry that PACAP inhibited serum deprivation-induced apoptosis in RGC-5 cells. The proportions of apoptotic cells and cells with mitochondria depolarization were significantly decreased with PACAP treatment. Western blot assays demonstrated that PACAP increased the levels of Bcl-2 and inhibited the compensatory increase of PAC1. Together, these data indicate protective effects of PACAP against serum deprivation-induced apoptosis in RGCs, and that the mechanism of this action is associated with maintaining mitochondrial function.展开更多
BACKGROUND Hypoganglionosis is a rare condition that most often presents with abnormal gastrointestinal transit and usually arises in early childhood or adolescence. Two types have been described(Type I and Type II). ...BACKGROUND Hypoganglionosis is a rare condition that most often presents with abnormal gastrointestinal transit and usually arises in early childhood or adolescence. Two types have been described(Type I and Type II). The adult-onset form(acquired hypoganglionosis) is extremely uncommon and is thought to arise due to cellular remodelling as a result of chronic inflammation. It differs from Hirschprung's disease in that there is a reduction in ganglion cells in the colonic neural plexuses as opposed to being completely absent.CASE SUMMARY A 31 year-old male presented to hospital with recurrent abdominal pain and vomiting over thirteen months. Abdominal computed tomography scans demonstrated thickening and stranding affecting the transverse, descending and sigmoid colon. Endoscopic appearances were non-specific but confirmed a mixed picture of mucosal inflammation and necrosis in various stages of healing.Numerous investigations were performed to elucidate an underlying aetiology but neither an infective nor ischaemic cause could be proven. Biopsy features were not typical of inflammatory bowel disease. Due to persistence of his symptoms and failure of medical management, a segmental colectomy was performed. Histological examination of the specimen revealed an unexpected finding of segmental hypoganglionosis. Complete surgical excision of the diseased segment of colon was curative and since his operation the patient has had no recurrence of symptoms requiring hospitalisation.CONCLUSION Our case serves to raise awareness of acquired hypoganglionosis as a rare condition that can result from chronic colitis.展开更多
Objective To investigate the regulatory effects of nerve growth factor （NGF） on basal and capsaicin-induced release of neuropeptide substance P （SP） in primary cultured embryonic rat dorsal root ganglion （DRG） n...Objective To investigate the regulatory effects of nerve growth factor （NGF） on basal and capsaicin-induced release of neuropeptide substance P （SP） in primary cultured embryonic rat dorsal root ganglion （DRG） neurons. Methods DRGs were dissected from 15-day-old embryonic Wistar rats. DRG neurons were dissociated and cultured, and then exposed to different concentrations of NGF （10 ng/mL, 30 ng/mL, or 100 ng/mL） for 72 h. The neurons cultured in media without NGF served as control. RT-PCR were used for detecting the mRNAs of SP and vanilloid receptor 1 （VR1） in the DRG neurons. The SP basal and capsaicin （100 nmol/L）-induced release in the culture were measured by radioimmunoassay （RIA）. Results SP mRNA and VR1 mRNA expression increased in primary cultured DRG neurons in a dose-dependent manner of NGF. Both basal release and capsaicin-evoked release of SP increased in NGF-treated DRG neurons compared with in control group. The capsaicin-evoked release of SP also increased in a dose-dependent manner of NGF. Conclusion NGF may promote both basal release and capsaicin-evoked release of SP. NGF might increase the sensitivity of nociceptors by increasing the SP mRNA or VR1 mRNA.展开更多
Objective To screen and identify differentially expressed genes in the dorsal root ganglion （DRG） in early experimental diabetic rats. Methods Diabetic model rats were induced by single intraperitoneal injection of ...Objective To screen and identify differentially expressed genes in the dorsal root ganglion （DRG） in early experimental diabetic rats. Methods Diabetic model rats were induced by single intraperitoneal injection of streptozotocin （STZ）. At the second week after STZ injection, the sensory nerve conduction velocities （SNCV） of sciatic nerve were measured as an indicator of neuropathy. The technique of silver-staining mRNA differential display polymerase chain reaction （DD-PCR） was used to detect the levels of differentially expressed genes in rat DRG. The cDNA fragments that displayed differentially were identified by reverse-hybridization, cloned and sequenced subsequently, and then confirmed by Northern blot. Results The SNCV in the diabetic model group [n = 9, （45.25±10.38） m/s] reduced obviously compared with the control group [n = 8, （60.10± 11.92） m/s] （P 〈 0.05）. Seven distinct cDNA clones, one was up-regulated gene and the others were downregulated ones, were isolated by silver-staining mRNA differential display method and confirmed by Northern blot. According to the results of sequence alignment with GenBank data, majority of the clones had no significant sequence similarity to previously reported genes except only one that showed high homology to 6-pyruvoyl-tetrahydropterin synthase mRNA （accession No., BC059140）, which had not been reported to relate to diabetic neuropathy. Conclusion These differentially expressed genes in the diabetic DRG may contribute to the pathogenesis of diabetic peripheral neuropathy.展开更多
The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic mac...The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery.In this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.The trial protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Beihua University with approval No.(2023)(26)on April 25,2023,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR2300072478,June 14,2023,protocol version:2.0).展开更多
Objective To investigate the involvement of transient receptor potential vanilloid receptor 1 （TRPV1） in the facial inflammatory pain in relation to thermal hyperalgesia and cold pain sensation. Methods Facial infla...Objective To investigate the involvement of transient receptor potential vanilloid receptor 1 （TRPV1） in the facial inflammatory pain in relation to thermal hyperalgesia and cold pain sensation. Methods Facial inflammatory pain model was developed by subcutaneous injection of turpentine oil （TO） into rat facial area. Head withdrawal thermal latency （HWTL） and head withdrawal cold latency （HWCL） were measured once a day for 21 d after TO treatment using thermal and cold measurement apparatus. The immunohistochemical staining, cell-size frequency analysis and the survey of average optical density （OD） value were used to observe the changes of TRPV1 expression in the neurons of the trigeminal ganglion （TG）, peripheral nerve fibers in the vibrissal pad, and central projection processes in the trigeminal sensory nuclei caudalis （Vc） on day 3, 5, 7, 14, and 21 after TO injection. Results HWTL and HWCL decreased significantly from day 1 to day 14 after TO injection with the lowest value on day 5 and day 3, respectively, and both recovered on day 21. The number of TRPV1-labeled neurons increased remarkably from day 1 to day 14 with a peak on day 7, and returned back to the normal level on day 21. In control rats, only small and medium-sized TG neurons were immunoreactive （IR） to TRPV1, and the TRPV1-IR terminals were abundant in both the vibrissal pad and the Vc. Within 2 weeks of inflammation, the expression of TRPV1 in small and medium-sized TG neurons increased obviously. Also the TRPV1 stained terminals and fibers appeared more frequent and denser in both the vibrissal pad skin and throughout laminae Ⅰ and the outer zone of laminae Ⅱ （Ⅱo） of Vc. Conclusion Facial inflammatory pain could induce hyperalgesia to noxious heat and cold stimuli, and result in increase of the numbers of TRPV1 positive TG neurons and the peripheral and central terminals of TG. These results suggest that the phenotypic changes of TRPV1 expression in small and medium-sized TG neurons and terminals might play an important role in the development and maintenance of TO-induced inflammatory thermal hyperalgesia and cold pain sensation.展开更多
Objective To determine the effects of insulin-like growth factor-1 （IGF-1） on the expression of preprotachykinin （PPT） mRNA encoding substance P （SP） and calcitonin gene-related peptide （CGRP） mRNA in cultured...Objective To determine the effects of insulin-like growth factor-1 （IGF-1） on the expression of preprotachykinin （PPT） mRNA encoding substance P （SP） and calcitonin gene-related peptide （CGRP） mRNA in cultured dorsal root ganglion （DRG） neurons with excitotoxicity induced by glutamate （Glu）. Methods DRGs were dissected from embryonic day 15 Wistar rats. DRG neurons were dissociated and cultured for 48 h and then exposed to Glu （0.2 mmol/L） or Glu （0.2 mmol/L） plus IGF- 1 （5 nmol/L, 10 nmol/L and 20 nmol/L） for 12 h. The DRG neurons in control group were exposed to only growth media throughout the experiment. After that, the living DRG neurons were observed under inverted phase contrast microscope and microphotographs were taken. The expression levels of PPT and CGRP mRNAs were detected by reverse transcriptionpolymerase chain reaction （RT-PCR）. Results IGF-1 could inhibit Glu-induced shortening of neurite. Besides, IGF-1 could significantly increase the levels ofPPT mRNA and CGRP mRNA in primary cultured DRG neurons with Glu-induced excitotoxicity, in a dose-dependent manner. Conclusion IGF-1 may exert neuroprotective effects on DRG neurons against Glu-induced excitotoxicity, probably through regulating the expression levels of PPT and CGRP mRNAs.展开更多
基金supported by a Ph.D.scholarship from the YLSY program of the Republic of Turkiye,Ministry of National Educationfunded by Fight for Sight UK,grant reference#5183/5184。
文摘Glaucoma is characterized by chronic progressive optic nerve damage and retinal ganglion cell death.Although extensive research has been conducted on neuroprotection for retinal ganglion cells,there is still no treatment for clinical use.Recent evidence shows that extracellular vesicles isolated from a variety of stem cells are efficacious in retinal ganglion cell neuroprotection.In this study,we tested the novel extracellular vesicle source of the retinal progenitor R-28 cell line in vitro and in vivo.We isolated and characterized extracellular vesicles from R-28 cells and tested their therapeutic efficacy in terms of retinal ganglion cell survival in vitro and in an in vivo glaucoma model,measuring retinal ganglion cell survival and preservation of their axons.Additionally,we tested extracellular vesicles for their neuroprotective capacity in retinal ganglion cells differentiated from human embryonic stem cells.Finally,we investigated miRNA changes in retinal ganglion cells with R-28 extracellular vesicle treatment,and predicted possible pathways that may be modulated.R-28 extracellular vesicles improved retinal ganglion cell survival but failed to preserve axons significantly.Moreover,the results also illustrated the neuroprotection of R-28 extracellular vesicles on human retinal ganglion cells.Finally,we also showed changes in hsa-miRNA-4443,hsa-miRNA-216a-5p,hsa-let-7e-5p,hsa-miRNA-374b-5p,hsa-miRNA-331-3p,and hsa-miRNA-421 expressions,which may have neuroprotective potential on retinal ganglion cell degeneration.This study will pave the way for miRNA and extracellular vesicle-based neuroprotective therapies for glaucoma.
文摘Calcium (Ca^(2+)) is a key intracellular messenger involved in a variety of cellular functions.Intracellular Ca^(2+)dysregulation drives neuron cell death in multiple degenerative diseases and traumatic conditions.Retinal ganglion cell(RGC) degeneration occurs in blinding diseases such as glaucoma and other optic neuropathies.
基金supported by the National Natural Science Foundation of China,Nos.81800919(to YX),82171140(to PW)the International Cooperation and Exchange of the National Natural Science Foundation of China,Nos.82020108008(to HS),81720108010(to SY).
文摘Aminoglycosides are a widely used class of antibacterials renowned for their effectiveness and broad antimicrobial spectrum.However,their use leads to irreversible hearing damage by causing apoptosis of hair cells as their direct target.In addition,the hearing damage caused by aminoglycosides involves damage of spiral ganglion neurons upon exposure.To investigate the mechanisms underlying spiral ganglion neuron degeneration induced by aminoglycosides,we used a C57BL/6J mouse model treated with kanamycin.We found that the mice exhibited auditory deficits following the acute loss of outer hair cells.Spiral ganglion neurons displayed hallmarks of pyroptosis and exhibited progressive degeneration over time.Transcriptomic profiling of these neurons showed significant upregulation of genes associated with inflammation and immune response,particularly those related to the NLRP3 inflammasome.Activation of the canonical pyroptotic pathway in spiral ganglion neurons was observed,accompanied by infiltration of macrophages and the release of proinflammatory cytokines.Pharmacological intervention targeting NLRP3 using Mcc950 and genetic intervention using NLRP3 knockout ameliorated spiral ganglion neuron degeneration in the injury model.These findings suggest that NLRP3 inflammasome-mediated pyroptosis plays a role in aminoglycoside-induced spiral ganglion neuron degeneration.Inhibition of this pathway may offer a potential therapeutic strategy for treating sensorineural hearing loss by reducing spiral ganglion neuron degeneration.
基金supported by the National Natural Science Foundation of China,No.82271114the Natural Science Foundation of Zhejiang Province of China,No.LZ22H120001(both to ZLC).
文摘Several studies have found that transplantation of neural progenitor cells(NPCs)promotes the survival of injured neurons.However,a poor integration rate and high risk of tumorigenicity after cell transplantation limits their clinical application.Small extracellular vesicles(sEVs)contain bioactive molecules for neuronal protection and regeneration.Previous studies have shown that stem/progenitor cell-derived sEVs can promote neuronal survival and recovery of neurological function in neurodegenerative eye diseases and other eye diseases.In this study,we intravitreally transplanted sEVs derived from human induced pluripotent stem cells(hiPSCs)and hiPSCs-differentiated NPCs(hiPSC-NPC)in a mouse model of optic nerve crush.Our results show that these intravitreally injected sEVs were ingested by retinal cells,especially those localized in the ganglion cell layer.Treatment with hiPSC-NPC-derived sEVs mitigated optic nerve crush-induced retinal ganglion cell degeneration,and regulated the retinal microenvironment by inhibiting excessive activation of microglia.Component analysis further revealed that hiPSC-NPC derived sEVs transported neuroprotective and anti-inflammatory miRNA cargos to target cells,which had protective effects on RGCs after optic nerve injury.These findings suggest that sEVs derived from hiPSC-NPC are a promising cell-free therapeutic strategy for optic neuropathy.
基金supported by the Basic Research Project for Higher Education Institutions of Liaoning Provincial Department of Education(Youth Project)(LJ212410160055)Foundation of Education Department of Liaoning Province of China(LJKMZ20221241)+1 种基金The National Natural Science Foundation of China(81571383)Natural Science Foundation of Liaoning Province of China(2023-MS-312)。
文摘Salidroside(Sal),is one of the important food supplements from the traditional Chinese medicine Integripetal rhodiola herb,encapsulating significant anti-oxidative stress,anti-ferroptosis,and neuroprotective attributes.Notwithstanding these latent virtues,the ramifications of Sal on retinal ganglion cells(RGCs)impairment during the incipient stages of diabetic retinopathy(DR)remain equivocal.The purpose of this study was to investigate inhibitory effect of Sal on ferroptosis of RGCs in db/db mice.Within the research conducted,Sal was administered via gavage,and observations were made 8 weeks post-treatment.Retinal samples were collected for analysis.The results evidenced that Sal ameliorated blood glucose levels,attenuated RGCs destruction,and augmented visual functionality in db/db mice.Additionally,Sal exerted an anti-ferroptosis impact on the RGCs in the db/db mice.Successive discoveries have outlined the involvement of the HIF-1α/HO-1 signaling pathway in this protective mechanism.Ferroptosis of RGCs has a contributory effect on the development of DR,in part through the HIF-1α/HO-1 pathway.Intriguingly,Sal reversed the alterations in the HIF-1α/HO-1 pathway in db/db mice and displayed prospective advantageous effects on DR.Sal mitigated RGCs ferroptosis by reducing blood sugar and impeding the HIF-1α/HO-1 signaling pathway,thereby improving DR.Thus,Sal shows potential for use as a pharmaceutical and nutraceutical for DR.
基金Supported by National Natural Science Foundation of China(No.82070964)Shaanxi Provincial Outstanding Youth Science Foundation Project(No.2022JC-60)+1 种基金Shaanxi International Science and Technology Cooperation Program Project(No.2024GHYBXM-20)Shaanxi Provincial Education Department Youth Innovation Team Research Project(No.23JP151).
文摘Glaucoma is a group of diseases characterized by progressive optic nerve degeneration,with the characteristic pathological change being death of retinal ganglion cells(RGCs),which ultimately causes visual field loss and irreversible blindness.Elevated intraocular pressure(IOP)remains the most important risk factor for glaucoma,but the exact mechanism responsible for the death of RGCs is currently unknown.Neurotrophic factor deficiency,impaired mitochondrial structure and function,disrupted axonal transport,disturbed Ca2+homeostasis,and activation of apoptotic and autophagic pathways play important roles in RGC death in glaucoma.This review was conducted using Web of Science,PubMed,Project,and other databases to summarize the relevant mechanisms of death of RGCs in glaucoma,in addition to outlining protective treatments to improve the degradation of RGCs.
基金Supported by Science and Technology Research Project of Hubei Provincial Department of Education(No.B2021108).
文摘AIM:To explore the neuroprotective effects of high mobility group box 2(HMGB2)knockdown on retinal ganglion cells(RGCs)in the retinal ischemia-reperfusion injury(RIRI).METHODS:Oxygen-glucose deprivation(OGD)-injured RGCs from postnatal three-day C57BL/6 mice pups and high intraocular pressure(IOP)-induced RIRI mice were used as cellular and animal models of RIRI.The expression of HMGB2 in the retina of RIRI mice and OGD-injured RGCs was detected through reverse transcription-polymerase chain reaction(RT-qPCR)and Western blotting.The effects of HMGB2 silencing on the morphological changes,RGCs survival,and cell apoptosis in mouse retinal tissues were observed through H&E staining,immunofluorescence staining with RNA-binding protein with multiple splicing(RBPMS)antibody,and TUNEL staining,respectively.RGC viability and apoptosis were examined by CCK-8 and flow cytometry assays.The levels of proteins associated with NOD-like receptor thermal protein domain associated protein 3(NLRP3)-mediated pyroptosis[NLRP3,Caspase-1,GSDMD-N,interleukin(IL)-1β,IL-18]in vivo and in vitro were measured by Western blotting.RESULTS:HMGB2 protein and NLRP3 were upregulated in the retina of RIRI mice and OGD-injured RGCs(P<0.001).The retina was edematous,accompanied by disorganized cell arrangement and decreased thickness of all layers,and obvious vacuoles in ganglion cell layer.HMGB2 silencing alleviated the reduction in total retinal thickness and the severity of retinal tissue damage as well as suppressed RGC loss and retinal cell apoptosis in RIRI mice.OGD-induced RGC apoptosis was ameliorated after downregulation of HMGB2 in vitro.Intravitreal injection of the AAV-sh-HMGB2 and si-HMGB2 resulted in significantly decrease of NLRP3,Caspase-1,GSDMD-N,IL-1β,and IL-18 protein levels in the retinal tissues of RIRI mice and OGD-injured RGCs,respectively(all P<0.001).CONCLUSION:HMGB2 knockdown protects against RGC apoptosis and pyroptosis after RIRI through suppressing NLRP3 inflammasome activation.
文摘BACKGROUND Surgery is a common treatment for gastrointestinal tumors.General anesthesia(GA),while effective,can cause oxidative stress reactions and neuroinflammation,potentially leading to postoperative cognitive dysfunction and gastrointestinal dysfunction.The stellate ganglion block(SGB)can reduce sympathetic excitability and stress responses.This study aims to investigate whether combining SGB with GA can mitigate these adverse effects in patients undergoing gastrointestinal surgery.AIM To analyze the effects of SGB plus GA on hemodynamic stability,oxidative stress,neuroinflammation,cognitive function,and gastrointestinal function in patients undergoing gastrointestinal surgery.METHODS Patients undergoing gastrointestinal surgery between October 2022 and December 2024 were divided into two groups:A single GA group and an SGB combined with GA group(40 patients each).Hemodynamics,oxidative stress response,laboratory indices,cognitive function,and gastrointestinal function were compared preoperatively and 24 hours postoperatively between the two groups.Pain levels and complications were also recorded.RESULTS Before anesthesia induction,no significant differences were found in various indexes(including hemodynamics,oxidative stress indicators,laboratory indices,cognitive function scores,and gastrointestinal function indicators)between the two groups(P>0.05).At tracheal intubation,3 minutes after,and extubation,the GA-only group had significantly higher mean arterial pressure and heart rate postoperatively than preoperatively and compared to the SGB-GA combined group(P<0.05).Twentyfour hours postoperatively,oxidative stress indicators(malondialdehyde and nitric oxide)were significantly higher and superoxide dismutase was significantly lower in the GA group than in the SGB-GA combined group(P<0.05).Cognitive function scores[Mini-Mental State Examination and Montreal Cognitive Assessment(MoCA)]and gastrointestinal function indicators(motilin)were also significantly better in the SGB-GA combined group(P<0.05).The 24-hour postoperative MoCA score was 0.98 points higher in the SGB-GA combined group.No significant differences were found in the time of first postoperative ambulation,catheter removal time,and 24-hour postoperative pain between groups(P>0.05).CONCLUSION Combining SGB with GA can maintain perioperative hemodynamic stability,reduce oxidative stress and neuroinflammatory injury,and attenuate postoperative cognitive decline and gastrointestinal dysfunction in patients undergoing gastrointestinal surgery.
文摘BACKGROUND Anterior visual pathway lesions can cause severe visual loss.Optical coherence tomography(OCT)can detect ganglion cell complex(GCC)thinning,even with normal retinal nerve fiber layer(RNFL)thickness and subtle visual field changes.AIM To determine the proportion of eyes with RNFL and GCC thinning and their association with visual parameters in patients with brain tumors undergoing surgery.METHODS A prospective study was conducted on 37 patients(69 eyes)with peri-chiasmatic and chiasmatic brain tumors undergoing surgical decompression between February 2019 and June 2020 at a tertiary care institute.A comprehensive neuroophthalmological work-up,demographic and clinical profile documentation,and six-month postoperative follow-up weredone.Statistical analysis was significant at P<0.05.RESULTS Mean age was 35.14±11.98 years.The best and worst visual outcomes were associated with the craniopharyngioma and meningioma groups,respectively(P=0.008).There was an increase in the proportion of eyes with RNFL damage in the inferior quadrant(P=0.02).Maximum GCC thickness thinning was associated with severe visual impairment.The odds of having blindness in eyes with RNFL(inferior)and GCC loss were 0.96(P=0.003)and 0.95(P=0.03),respectively.GCC thickness showed a clinically positive correlation with visual acuity(r=-0.48,P<0.001)and field defect(r=-0.27,P=0.04)at six months postoperatively.The preoperative GCC thickness and the final postoperative visual outcome were plotted in an empirical ROC curve with area under the curve=0.754.The cut-off value of RNFL(inferior)and GCC,beyond which blindness could be prevented,was 73μm and 58μm,respectively.CONCLUSION In chiasmal compression,RNFL and GCC thickness measurements using OCT can be a useful prognostic indicator for assessing visual recovery.An eye with structural damage,with significant RNFL and GCC loss,is a predictive factor of blindness.A minimum preoperative RNFL and GCC thickness of 73μm and 58μm,respectively,can preserve vision after surgery.
文摘AIM:To explore the impact of insulin-like growth factor-1 receptorα(IGF-1Rα)on the differentiation fate of optic-cupderived retinal stem cells(OC-RSCs)into retinal ganglion cells(RGCs)in vitro.METHODS:OC-RSCs were isolated from optic cups of rats on embryonic day 12.5,and high-purity OC-RSCs were obtained by conditioned culture and passage.Differentiation of OC-RSCs into RGCs under different serum concentrations was examined using flow cytometry,and the serum concentration with high interference with differentiation ratio was selected.Furthermore,the effect of blocking IGF-1Rαon the differentiation of OC-RSCs into RGCs was analyzed through immunocytochemistry and Western blotting.RESULTS:Immunohistochemical analysis revealed IGF-1Rαwas highly expressed in rat embryos at day 12.5.OC-RSCs were isolated and purified,and high-purity OCRSCs were obtained.When 2.5%serum was administered,the ratio of differentiated RGCs(Thy-1.1 positive)decreased significantly,and the results of immunoblotting also confirmed the blockade of IGF-1Rαreduced Thy-1.1 protein expression.CONCLUSION:IGF-1Rαblocking can reduce the differentiation of OC-RSCs into RGCs.
文摘Immunoreactivity (IR) for vasoactive intestinal polypeptide (VIP) of cranial parasympathetic ganglia of the rat was observed with indirect immunofluorescent method. It was found that there were VIP IR principal neurons in the ciliary, pterygopalatine, and otic ganglia. The highest positive ratio of VIP IR cells was located in the ciliary ganglia (34.8%), followed by that in the pterygopalatine ganglia(17.0%), and the lowest was found in the otic ganglia (15.4%). VIP IR small intensely fluorescent (SIF) cells and nerve fibers were not observed. Distributive characteristics of neuropeptides and functional significance of VIP in cranial parasympathetic ganglia were discussed.
基金InternationalFoundationforScience Sweden +1 种基金D/ 2 1 69_1 FoundationoftheEducationMinistryofChina .
文摘The development, cytological characters and ultrastructure of phloem ganglion in the nodal region of Phyllostachys edulis (Carr.) H. de Lehaie, a most economically important bamboo, were investigated and the possible physiological function of this special structure was proposed. The phloem ganglion derived directly from procambium is situated at the sites where the vascular bundle forks and is present in pairs. The phloem ganglion is spindle_like in appearance and usually consists of 4 to 6 layers. Two kinds of cells in the ganglion could be distinguished. In the middle, there are two layers of filiform cells with pointed ends so that there are no normal sieve plates. Nevertheless, there are many pits on the lateral wall of the filiform cells. The other type of cells located at both ends of the spindle which possess an intermediate form between the filiform cell and the normal sieve tube. The walls of these cells towards the filiform cells are strongly convex forming a special sieve plate. Ultrastructure study showed that cells in the ganglion are connected by enriched plasmodesma. During early differentiation, the paramural body and the ingrowth of cell wall could be observed. It indicates that the cells of phloem ganglion have the character of transfer cells. The organelles in the mature cells are mainly plastids with abundant accumulation of proteins of crystalline structure. The above_mentioned results suggest that the physiological function of the phloem ganglion is closely related with substance transport.
基金Supported by Project of Science and Technology Bureau,Yichang,Hubei:A:01301-46
文摘Objective To explore the best therapeutic method in the treatment of peripheral facial paralysis. Methods One hundred and twenty cases were randomized into a conventional acupuncture group [Yangbai （阳白 GB 24）, Sibai （四白 ST 2）, Yingxiang （迎香 LI 20）, etc.], a Renying （人迎ST 9） acupuncture group and an operation ＋ acupuncture group [acupuncture at ST 9 as the main acupoint and the stellate ganglion block （SGB）], 40 cases in each one. The treatment was given once a day, 7 treatments made one session. After 3 sessions of treatment, the latency and the amplitude of the direct stimulation evoked potential of the facial nerve （ENoG） were compared before and after treatment in three groups, as well as R2 and R2 values of blink reflex （BR）. The total clinical efficacy was assessed. Results The latency of ENoG was shortened and the amplitude was increased significantly in three groups. After treatment, ENoG latency was lower significantly in the operation ＋ acupuncture group as compared with that in the conventional acupuncture group （P〈0.05）. In the Renying （人迎 ST 9） acupuncture group, the amplitude of ENoG was increased as compared with P〈0.05）. After treatment in three groups, those in the other two groups （all R2 and R2 values were decreased significantly. The differences in R1 and R2 values in the Renying （人迎 ST 9） acupuncture group and the operation ＋ acupuncture group before and after treatment were bigger than those in the conventional acupuncture group （all P〈0.05）, and the difference in R2 value in the operation ＋ acupuncture group was bigger than that in the Renying （人迎 ST 9） acupuncture group （P〈O.05）. The clinical markedly effective and curative rate was 87.5% （35/40） in the operation ＋ acupuncture group, which was superior to 77.5% （32/40） in the Renying （）人迎 ST 9）acupuncture group and higher significantly than 65.0% （26/40） in the conventional acupuncture group （P〈0.05）. Conclusion Compared with the conventional acupuncture, the efficacy on peripheral facial paralysis is much better in the Renying （人迎 ST 9） acupuncture group and the operation ＋ acupuncture group. Moreover, the early reflex function of the damaged facial nerve is much better recovered in the operation ＋ acupuncture group as compared with that in the Renying （人迎 ST 9） acupuncture group.
基金supported by grants from the Medical Scientific Research Foundation of Guangdong Province of China,No.A2016271the Natural Science Foundation of Guangdong Province of China,No.2016A030313208the Science and Technology Planning Project of Guangdong Province of China,No.2014A020212393
文摘Pituitary adenylate cyclase-activating polypeptide（PACAP） is an endogenous peptide with neuroprotective effects on retinal neurons, but the precise mechanism underlying these effects remains unknown. Considering the abundance of mitochondria in retinal ganglion cells（RGCs）, we postulate that the protective effect of PACAP is associated with the regulation of mitochondrial function. RGC-5 cells were subjected to serum deprivation for 48 hours to induce apoptosis in the presence or absence of 100 nM PACAP. As revealed with the Cell Counting Kit-8 assay, PACAP at different concentrations significantly increased the viability of RGC-5 cells. PACAP also inhibited the excessive generation of reactive oxygen species in RGC-5 cells subjected to serum deprivation. We also showed by flow cytometry that PACAP inhibited serum deprivation-induced apoptosis in RGC-5 cells. The proportions of apoptotic cells and cells with mitochondria depolarization were significantly decreased with PACAP treatment. Western blot assays demonstrated that PACAP increased the levels of Bcl-2 and inhibited the compensatory increase of PAC1. Together, these data indicate protective effects of PACAP against serum deprivation-induced apoptosis in RGCs, and that the mechanism of this action is associated with maintaining mitochondrial function.
文摘BACKGROUND Hypoganglionosis is a rare condition that most often presents with abnormal gastrointestinal transit and usually arises in early childhood or adolescence. Two types have been described(Type I and Type II). The adult-onset form(acquired hypoganglionosis) is extremely uncommon and is thought to arise due to cellular remodelling as a result of chronic inflammation. It differs from Hirschprung's disease in that there is a reduction in ganglion cells in the colonic neural plexuses as opposed to being completely absent.CASE SUMMARY A 31 year-old male presented to hospital with recurrent abdominal pain and vomiting over thirteen months. Abdominal computed tomography scans demonstrated thickening and stranding affecting the transverse, descending and sigmoid colon. Endoscopic appearances were non-specific but confirmed a mixed picture of mucosal inflammation and necrosis in various stages of healing.Numerous investigations were performed to elucidate an underlying aetiology but neither an infective nor ischaemic cause could be proven. Biopsy features were not typical of inflammatory bowel disease. Due to persistence of his symptoms and failure of medical management, a segmental colectomy was performed. Histological examination of the specimen revealed an unexpected finding of segmental hypoganglionosis. Complete surgical excision of the diseased segment of colon was curative and since his operation the patient has had no recurrence of symptoms requiring hospitalisation.CONCLUSION Our case serves to raise awareness of acquired hypoganglionosis as a rare condition that can result from chronic colitis.
文摘Objective To investigate the regulatory effects of nerve growth factor （NGF） on basal and capsaicin-induced release of neuropeptide substance P （SP） in primary cultured embryonic rat dorsal root ganglion （DRG） neurons. Methods DRGs were dissected from 15-day-old embryonic Wistar rats. DRG neurons were dissociated and cultured, and then exposed to different concentrations of NGF （10 ng/mL, 30 ng/mL, or 100 ng/mL） for 72 h. The neurons cultured in media without NGF served as control. RT-PCR were used for detecting the mRNAs of SP and vanilloid receptor 1 （VR1） in the DRG neurons. The SP basal and capsaicin （100 nmol/L）-induced release in the culture were measured by radioimmunoassay （RIA）. Results SP mRNA and VR1 mRNA expression increased in primary cultured DRG neurons in a dose-dependent manner of NGF. Both basal release and capsaicin-evoked release of SP increased in NGF-treated DRG neurons compared with in control group. The capsaicin-evoked release of SP also increased in a dose-dependent manner of NGF. Conclusion NGF may promote both basal release and capsaicin-evoked release of SP. NGF might increase the sensitivity of nociceptors by increasing the SP mRNA or VR1 mRNA.
基金the grant from Technical Program of Social Development ofNantong Municipality (No.S30043)the Natural ScienceFoundation of Nantong University (No. 05Z084)
文摘Objective To screen and identify differentially expressed genes in the dorsal root ganglion （DRG） in early experimental diabetic rats. Methods Diabetic model rats were induced by single intraperitoneal injection of streptozotocin （STZ）. At the second week after STZ injection, the sensory nerve conduction velocities （SNCV） of sciatic nerve were measured as an indicator of neuropathy. The technique of silver-staining mRNA differential display polymerase chain reaction （DD-PCR） was used to detect the levels of differentially expressed genes in rat DRG. The cDNA fragments that displayed differentially were identified by reverse-hybridization, cloned and sequenced subsequently, and then confirmed by Northern blot. Results The SNCV in the diabetic model group [n = 9, （45.25±10.38） m/s] reduced obviously compared with the control group [n = 8, （60.10± 11.92） m/s] （P 〈 0.05）. Seven distinct cDNA clones, one was up-regulated gene and the others were downregulated ones, were isolated by silver-staining mRNA differential display method and confirmed by Northern blot. According to the results of sequence alignment with GenBank data, majority of the clones had no significant sequence similarity to previously reported genes except only one that showed high homology to 6-pyruvoyl-tetrahydropterin synthase mRNA （accession No., BC059140）, which had not been reported to relate to diabetic neuropathy. Conclusion These differentially expressed genes in the diabetic DRG may contribute to the pathogenesis of diabetic peripheral neuropathy.
基金supported by Science and Technology Research Project of Jilin Provincial Department of Education,No.JJKH20220072KJ(to XL)Science and Technology Development Program of Jilin Province,No.20200201495JC(to YL)。
文摘The integrity of retinal ganglion cells is tightly associated with diabetic macular degeneration that leads to damage and death of retinal ganglion cells,affecting vision.The major clinical treatments for diabetic macular edema are anti-vascular endothelial growth factor drugs and laser photocoagulation.However,although the macular thickness can be normalized with each of these two therapies used alone,the vision does not improve in many patients.This might result from the incomplete recovery of retinal ganglion cell injury.Therefore,a prospective,non-randomized,controlled clinical trial was designed to investigate the effect of anti-vascular endothelial growth factor drugs combined with laser photocoagulation on the integrity of retinal ganglion cells in patients with diabetic macular edema and its relationship with vision recovery.In this trial,150 patients with diabetic macular edema will be equally divided into three groups according to therapeutic methods,followed by treatment with anti-vascular endothelial growth factor drugs,laser photocoagulation therapy,and their combination.All patients will be followed up for 12 months.The primary outcome measure is retinal ganglion cell-inner plexiform layer thickness at 12 months after treatment.The secondary outcome measures include retinal ganglion cell-inner plexiform layer thickness before and 1,3,6,and 9 months after treatment,retinal nerve fiber layer thickness,best-corrected visual acuity,macular area thickness,and choroidal thickness before and 1,3,6,9,and 12 months after treatment.Safety measure is the incidence of adverse events at 1,3,6,9,and 12 months after treatment.The study protocol hopes to validate the better efficacy and safety of the combined treatment in patients with diabetic macula compared with the other two monotherapies alone during the 12-month follow-up period.The trial is designed to focus on clarifying the time-effect relationship between imaging measures related to the integrity of retinal ganglion cells and best-corrected visual acuity.The trial protocol was approved by the Medical Ethics Committee of the Affiliated Hospital of Beihua University with approval No.(2023)(26)on April 25,2023,and was registered with the Chinese Clinical Trial Registry(registration number:ChiCTR2300072478,June 14,2023,protocol version:2.0).
基金supported by the National Natural Science Foundation of China(No.30570629)China-Dutch Joint Research Project(No.05CDP030)
文摘Objective To investigate the involvement of transient receptor potential vanilloid receptor 1 （TRPV1） in the facial inflammatory pain in relation to thermal hyperalgesia and cold pain sensation. Methods Facial inflammatory pain model was developed by subcutaneous injection of turpentine oil （TO） into rat facial area. Head withdrawal thermal latency （HWTL） and head withdrawal cold latency （HWCL） were measured once a day for 21 d after TO treatment using thermal and cold measurement apparatus. The immunohistochemical staining, cell-size frequency analysis and the survey of average optical density （OD） value were used to observe the changes of TRPV1 expression in the neurons of the trigeminal ganglion （TG）, peripheral nerve fibers in the vibrissal pad, and central projection processes in the trigeminal sensory nuclei caudalis （Vc） on day 3, 5, 7, 14, and 21 after TO injection. Results HWTL and HWCL decreased significantly from day 1 to day 14 after TO injection with the lowest value on day 5 and day 3, respectively, and both recovered on day 21. The number of TRPV1-labeled neurons increased remarkably from day 1 to day 14 with a peak on day 7, and returned back to the normal level on day 21. In control rats, only small and medium-sized TG neurons were immunoreactive （IR） to TRPV1, and the TRPV1-IR terminals were abundant in both the vibrissal pad and the Vc. Within 2 weeks of inflammation, the expression of TRPV1 in small and medium-sized TG neurons increased obviously. Also the TRPV1 stained terminals and fibers appeared more frequent and denser in both the vibrissal pad skin and throughout laminae Ⅰ and the outer zone of laminae Ⅱ （Ⅱo） of Vc. Conclusion Facial inflammatory pain could induce hyperalgesia to noxious heat and cold stimuli, and result in increase of the numbers of TRPV1 positive TG neurons and the peripheral and central terminals of TG. These results suggest that the phenotypic changes of TRPV1 expression in small and medium-sized TG neurons and terminals might play an important role in the development and maintenance of TO-induced inflammatory thermal hyperalgesia and cold pain sensation.
基金supported by the Natural Sciences Foundation of Shandong Province, China(No. Z2006C06)the Science and Technology Development Project of Jinan Municipality of Shandong Province,China (No. 200705083, 200807046)
文摘Objective To determine the effects of insulin-like growth factor-1 （IGF-1） on the expression of preprotachykinin （PPT） mRNA encoding substance P （SP） and calcitonin gene-related peptide （CGRP） mRNA in cultured dorsal root ganglion （DRG） neurons with excitotoxicity induced by glutamate （Glu）. Methods DRGs were dissected from embryonic day 15 Wistar rats. DRG neurons were dissociated and cultured for 48 h and then exposed to Glu （0.2 mmol/L） or Glu （0.2 mmol/L） plus IGF- 1 （5 nmol/L, 10 nmol/L and 20 nmol/L） for 12 h. The DRG neurons in control group were exposed to only growth media throughout the experiment. After that, the living DRG neurons were observed under inverted phase contrast microscope and microphotographs were taken. The expression levels of PPT and CGRP mRNAs were detected by reverse transcriptionpolymerase chain reaction （RT-PCR）. Results IGF-1 could inhibit Glu-induced shortening of neurite. Besides, IGF-1 could significantly increase the levels ofPPT mRNA and CGRP mRNA in primary cultured DRG neurons with Glu-induced excitotoxicity, in a dose-dependent manner. Conclusion IGF-1 may exert neuroprotective effects on DRG neurons against Glu-induced excitotoxicity, probably through regulating the expression levels of PPT and CGRP mRNAs.
