AIM:To investigate the effects of adenosine triphosphate(ATP)and melatonin,which have antioxidant and antiinflammatory activities,on potential 5-fluorouracil(5-FU)-induced optic nerve damage in rats.METHODS:Twenty-fou...AIM:To investigate the effects of adenosine triphosphate(ATP)and melatonin,which have antioxidant and antiinflammatory activities,on potential 5-fluorouracil(5-FU)-induced optic nerve damage in rats.METHODS:Twenty-four rats were categorized into four groups of six rats:healthy(HG),5-FU(FUG),ATP+5-FU(AFU),and melatonin+5-FU(MFU).ATP(4 mg/kg)and melatonin(10 mg/kg)were administered intraperitoneally and orally,respectively.One hour after ATP and melatonin administration,rats in the AFU,MFU,and FUG were intraperitoneally injected with 5-FU(100 mg/kg).ATP and melatonin were administered once daily for 10d.5-FU was administered at a single dose on days 1,3,and 5 of the experiment.After 10d,the rats were euthanized and optic nerve tissues were extracted.Optic nerve tissues were biochemically and histopathologically examined.RESULTS:ATP and melatonin treatments inhibited the increase in malondialdehyde(MDA)and interleukin-6(IL-6)levels,which were elevated in the FUG.The treatments also prevented the decrease in total glutathione(tGSH)levels and the superoxide dismutase(SOD)and catalase(CAT)activities(P<0.001).This inhibition was higher in the ATP group than in the melatonin group(P<0.001).ATP prevented histopathological damage better than melatonin(P<0.05).CONCLUSION:ATP and melatonin have the potential to be used in alleviating 5-FU-induced optic nerve damage.In addition,ATP treatment shows better protective effects than melatonin.展开更多
Rho-associated kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase RhoA. The Rho/ROCK pathway is closely related to the pathogenesis of several central nervous syst...Rho-associated kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase RhoA. The Rho/ROCK pathway is closely related to the pathogenesis of several central nervous system (CNS) disorders, and involved in many aspects of neuronal functions including neurite outgrowth and retraction. In the adult CNS, the damaged neuron regeneration is very difficult due to the presence of myelin-associated axon growth inhibitors such as Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (Omgp), etc. The effects of these axon growth inhibitors are reversed by blocking the Rho/ROCK pathway 47 vitro, and the inhibition of Rho/ROCK pathway can promote axon regeneration and functional recovery in the injured CNS in viva In addition, the therapeutic effects of the Rho/ROCK inhibitors have also been demonstrated in some animal models and the Rho/ROCK pathway becomes an attractive target for the development of drugs for treating CNS disorders. In this review, we summarized on the effect of the Rho and the downstream factor ROCK in neural regeneration, and the potential therapeutic effect of Rho/ROCK inhibitors in the survival and axonal regeneration of retinal ganglion cell was also discussed.展开更多
Retinal ganglion cells are the bridging neurons between the eye and the central nervous system,transmitting visual signals to the brain.The injury and loss of retinal ganglion cells are the primary pathological change...Retinal ganglion cells are the bridging neurons between the eye and the central nervous system,transmitting visual signals to the brain.The injury and loss of retinal ganglion cells are the primary pathological changes in several retinal degenerative diseases,including glaucoma,ischemic optic neuropathy,diabetic neuropathy,and optic neuritis.In mammals,injured retinal ganglion cells lack regenerative capacity and undergo apoptotic cell death within a few days of injury.Additionally,these cells exhibit limited regenerative ability,ultimately contributing to vision impairment and potentially leading to blindness.Currently,the only effective clinical treatment for glaucoma is to prevent vision loss by lowering intraocular pressure through medications or surgery;however,this approach cannot halt the effect of retinal ganglion cell loss on visual function.This review comprehensively investigates the mechanisms underlying retinal ganglion cell degeneration in retinal degenerative diseases and further explores the current status and potential of cell replacement therapy for regenerating retinal ganglion cells.As our understanding of the complex processes involved in retinal ganglion cell degeneration deepens,we can explore new treatment strategies,such as cell transplantation,which may offer more effective ways to mitigate the effect of retinal degenerative diseases on vision.展开更多
Lamotrigine(LTG)is a widely used drug for the treatment of epilepsy.Emerging clinical evidence suggests that LTG may improve cognitive function in patients with Alzheimer’s disease.However,the underlying molecular me...Lamotrigine(LTG)is a widely used drug for the treatment of epilepsy.Emerging clinical evidence suggests that LTG may improve cognitive function in patients with Alzheimer’s disease.However,the underlying molecular mechanisms remain unclear.In this study,amyloid precursor protein/presenilin 1(APP/PS1)double transgenic mice were used as a model of Alzheimer’s disease.Five-month-old APP/PS1 mice were intragastrically administered 30 mg/kg LTG or vehicle once per day for 3 successive months.The cognitive functions of animals were assessed using Morris water maze.Hyperphosphorylated tau and markers of synapse and glial cells were detected by western blot assay.The cell damage in the brain was investigated using hematoxylin and eosin staining.The levels of amyloid-βand the concentrations of interleukin-1β,interleukin-6 and tumor necrosis factor-αin the brain were measured using enzyme-linked immunosorbent assay.Differentially expressed genes in the brain after LTG treatment were analyzed by high-throughput RNA sequencing and real-time polymerase chain reaction.We found that LTG substantially improved spatial cognitive deficits of APP/PS1 mice;alleviated damage to synapses and nerve cells in the brain;and reduced amyloid-βlevels,tau protein hyperphosphorylation,and inflammatory responses.High-throughput RNA sequencing revealed that the beneficial effects of LTG on Alzheimer’s disease-related neuropathologies may have been mediated by the regulation of Ptgds,Cd74,Map3k1,Fosb,and Spp1 expression in the brain.These findings revealed potential molecular mechanisms by which LTG treatment improved Alzheimer’s disease.Furthermore,these data indicate that LTG may be a promising therapeutic drug for Alzheimer’s disease.展开更多
Organophosphate pesticide poisoning is an acute form of poisoning primarily found in underdeveloped regions.Its main clinical manifestations include muscarinic symptoms,nicotinic symptoms,and central nervous system di...Organophosphate pesticide poisoning is an acute form of poisoning primarily found in underdeveloped regions.Its main clinical manifestations include muscarinic symptoms,nicotinic symptoms,and central nervous system disturbances.This report presents a case of a middleaged female who developed extremely rare symptoms of optic nerve damage after ingesting a large amount of an organophosphate pesticide.展开更多
BACKGROUND： Schwann cells are the most commonly used cells for tissue-engineered nerves. However, autologous Schwann cells are of limited use in a clinical context, and allogeneic Schwann cells induce immunological r...BACKGROUND： Schwann cells are the most commonly used cells for tissue-engineered nerves. However, autologous Schwann cells are of limited use in a clinical context, and allogeneic Schwann cells induce immunological rejections. Cells that do not induce immunological rejections and that are relatively easy to acquire are urgently needed for transplantation. OBJECTIVE： To bridge sciatic nerve defects using tissue engineered nerves constructed with neural tissue-committed stem cells （NTCSCs） derived from bone marrow; to observe morphology and function of rat nerves following bridging; to determine the effect of autologous nerve transplantation, which serves as the gold standard for evaluating efficacy of tissue-engineered nerves. DESIGN, TIME AND SETTING： This randomized, controlled, animal experiment was performed in the Anatomical Laboratory and Biomedical Institute of the Second Military Medical University of Chinese PLA between September 2004 and April 2006. MATERIALS： Five Sprague Dawley rats, aged 1 month and weighing 100-150 g, were used for cell culture. Sixty Sprague Dawley rats aged 3 months and weighing 220-250 g, were used to establish neurological defect models. Nestin, neuron-specific enolase （NSE）, glial fibrillary acidic protein （GFAP）, and S-100 antibodies were provided by Santa Cruz Biotechnology, Inc., USA. Acellular nerve grafts were derived from dogs. METHODS： All rats, each with 1-cm gap created in the right sciatic nerve, were randomly assigned to three groups. Each group comprised 20 rats. Autograft nerve transplantation group： the severed 1-cm length nerve segment was reverted, but with the two ends exchanged; the proximal segment was sutured to the distal sciatic nerve stump and the distal segment to the proximal stump. Blank nerve scaffold transplantation group： a 1-cm length acellular nerve graft was used to bridge the sciatic nerve gap. NTCSC engineered nerve transplantation group： a 1-cm length acellular nerve graft, in which NTCSCs were inoculated, was used to bridge the sciatic nerve gap. MAIN OUTCOME MEASURES： Following surgery, sciatic nerve functional index and electrophysiology functions were evaluated for nerve conduction function, including conduction latency, conduction velocity, and action potential peak. Horseradish peroxidase （HRP, 20%） was injected into the gastrocnemius muscle to retrogradely label the 1-4 and L5 nerve ganglions, as well as neurons in the anterior horn of the spinal cord, in the three groups. Positive expression of nestin, NSE, GFAP, and S-100 were determined using an immunofluorescence double-labeling method. RESULTS： NTCSCs differentiated into neuronal-like cells and glial-like cells within 12 weeks after NTCSC engineered nerve transplantation. HRP retrograde tracing displayed a large amount of HRP-labeled neurons in I-45 nerve ganglions, as well as the anterior horn of the spinal cord, in both the autograft nerve transplantation and the NTCSC engineered nerve transplantation groups. However, few HRP-labeled neurons were detected in the blank nerve scaffold transplantation group. Nerve bridges in the autograft nerve transplantation and NTCSC engineered nerve transplantation groups exhibited similar morphology to normal nerves. Neither fractures or broken nerve bridges nor neuromas were found after bridging the sciatic nerve gap with NTCSCs-inoculated acellular nerve graft, indicating repair. Conduction latency, action potential, and conduction velocity in the NTCSC engineered nerve transplantation group were identical to the autograft nerve transplantation group （P 〉 0.05）, but significantly different from the blank nerve scaffold transplantation group （P 〈 0.05）. CONCLUSION＂ NTCSC tissue-engineered nerves were able to repair injured nerves and facilitated restoration of nerve conduction function, similar to autograft nerve transplantation. ＂展开更多
AIM:To investigate the effect of Bak Foong Pills(BFP) on the expression of β-amyloid(Aβ) in rats retina with optic nerve transaction,and its roles and possible mechanisms in protecting optic nerve damage.· METH...AIM:To investigate the effect of Bak Foong Pills(BFP) on the expression of β-amyloid(Aβ) in rats retina with optic nerve transaction,and its roles and possible mechanisms in protecting optic nerve damage.· METHODS:Seventy-two healthy,Sprague-Dawley,adult rats were randomly assigned to three groups:negative control group(control group),optic nerve transection group(model group) and BFP treatment group(BFP group,100μg/mL) followed by establishing optic nerve transection model.The expression of Aβ was measured at 48 hours by Western-blotting.Moreover,the expressions of Bcl-2,Bax and Caspase-3 mRNA were evaluated at 48 hours by reverse transcriptase polymerase chain reaction(RT-PCR).RESULTS:There were significant differences among the control,model and BFP groups in the expression of Aβ(all P <0.01).Aβ expression was significantly higher in the model and BFP groups than that in the control group(P < 0.01),with a more significant reduction in the BFP group than that in the model group(P <0.01).Moreover,there were also significant differences among the three groups in the expressions of Bcl-2/Bax(Bcl-2:anti-apoptotic;Bax:proapoptotic) and Caspase-3 mRNA(proapoptotic)(all P<0.01).Bcl-2/Bax ratio was significantly lower and Caspase-3 mRNA expression was significantly higher in the model and BFP groups than those in the control group(P <0.01),with a significant growing of Bcl-2/Bax and reduction of Caspase-3 in the BFP group than those in the model group(P<0.01).· CONCLUSION:BFP can down-regulate Aβ expression in retina and may inhibit apoptosis and protect optic nerve by enhancing Bcl-2/Bax ratio and inhibiting Caspase-3 pathway.展开更多
Based on network pharmacology,this study predicted the potential molecular mechanism and related pathways of the protective effect of traditional Chuanxiong Rhizoma,a traditional Chinese herb,on glaucomatous optic ner...Based on network pharmacology,this study predicted the potential molecular mechanism and related pathways of the protective effect of traditional Chuanxiong Rhizoma,a traditional Chinese herb,on glaucomatous optic nerve injury,and conducted in vitro experimental verification of the predicted results of network analysis.We analyzed the molecular mechanism of Chuanxiong Rhizoma in the potential treatment of glaucoma by revealing its main active ingredients and predicting its targets,so as to provide reference for subsequent basic research.Network pharmacological research results showed that the potential hub targets and key signaling pathways of Chuanxiong Rhizoma in the treatment of glaucoma were closely related to biological processes such as apoptosis,autophagy,inflammation,oxidative stress and angiogenesis.Molecular docking showed that many active ingredients,such as chrysophanol(CHR),myricanone and retinol,could combine well with their target proteins by intermolecular forces,especially CHR had strong binding ability with each target.We speculated that the main active component of Chuanxiong Rhizoma might be involved in the regulation of PI3K-Akt,Nod-like receptor,IL-4 and IL-13,MAPK,AGE-RAGE and neurotrophin signaling pathway by regulating of PI3K,Akt,TLR4,RAGE,NTRK2 and other key targets.Furthermore,it may achieve multi-directional intervention on apoptosis/autophagy,inflammation/immunity,oxidative stress and nutrient metabolism of axoplasma flow,and then delay the degeneration of optic nerve injury.In vitro experiments showed that the active component CHR of Chuanxiong Rhizoma could reverse the M1-type polarization and autophagy/apoptosis of mouse microglia(BV2)induced by lipopolysaccharide(LPS)at the transcriptional level.Meanwhile,the expression of inflammatory mediators IL-1βand TNF-αwas inhibited,and the mRNA level of anti-inflammatory factor IL-10 was significantly increased.In addition,CHR down-regulates activation of the RAGE-NOX4 pathway mediated by LPS in reducing oxidative stress.In this study,network pharmacology and molecular docking technology were integrated for the first time to explore the potential molecular mechanism of traditional Chinese herb“Chuanxiong Rhizoma”in the treatment on glaucoma,and CHR was innovatively proposed as an important ingredient in Chuanxiong Rhizoma that plays a protective role in the damage of optic nerve.Preliminary verification was conducted through in vitro experiments.The results suggest that Chuanxiong Rhizoma may interfere with autophagy and apoptosis,inhibit immune inflammation,as well as reduce oxidative stress in the treatment of glaucoma through the active components represented by CHR,so as to resist progressive optic nerve injury.Our study provides theoretical basis for the clinical use of Chinese herbal medicine or its extract in glaucoma,and also lays a solid foundation for the research of Chinese medicine in the field of optic nerve protection.展开更多
Nociception is an important physiological process that detects harmful signals and results in pain perception. In this review, we discuss important experimental evidence involving some TRP ion channels as molecular se...Nociception is an important physiological process that detects harmful signals and results in pain perception. In this review, we discuss important experimental evidence involving some TRP ion channels as molecular sensors of chemical, thermal, and mechanical noxious stimuli to evoke the pain and itch sensations. Among them are the TRPA1 channel, members of the vanilloid subfamily （TRPV1, TRPV3, and TRPV4）, and finally members of the melastatin group （TRPM2, TRPM3, and TRPMS）. Given that pain and itch are pro-survival, evolutionarily-honed protective mechanisms, care has to be exercised when developing inhibitory/modulatory com- pounds targeting specific pain/itch-TRPs so that physio- logical protective mechanisms are not disabled to a degree that stimulus-mediated injury can occur. Such events have impeded the development of safe and effective TRPV1- modulating compounds and have diverted substantial resources. A beneficial outcome can be readily accom- plished via simple dosing strategies, and also by incorpo- rating medicinal chemistry design features during compound design and synthesis. Beyond clinical use, where compounds that target more than one channel might have a place and possibly have advantageous features, highly specific and high-potency compounds will be helpful in mechanistic discovery at the structure-function level.展开更多
BACKGROUND The main pathological factor of cerebral infarction is atherosclerosis,which is the pathological process of chronic inflammatory diseases such as vascular smooth muscle hyperplasia,inflammatory cell infiltr...BACKGROUND The main pathological factor of cerebral infarction is atherosclerosis,which is the pathological process of chronic inflammatory diseases such as vascular smooth muscle hyperplasia,inflammatory cell infiltration,extracellular matrix increase,and thrombosis.At present,the focus of clinical treatment is anti-platelet aggregation and improving blood status,and current research is limited to improving symptoms only.AIM To observe the effect of sodium ozagrel and atorvastatin on type 2 diabetes patients with lacunar cerebral infarction.METHODS Eighty-two patients with type 2 diabetes and lacunar cerebral infarction admitted to our hospital from January 2018 to February 2020 were equally categorized into two groups according to their treatment method.The control group was administered atorvastatin,and the observation group was administered sodium ozagrel combined with atorvastatin.The National Institutes of Health stroke scale(NIHSS)score,activities of daily living(ADL)score,blood glucose,lipid levels,inflammatory factors,high-mobility group box 1(HMGB1)levels,paraoxonase-1(PON-1)levels,erythrocyte sedimentation rate(ESR),and macrophage migration inhibitory factor(MIF)levels were recorded before and after treatment.The total effective rate and adverse reaction rate of the two groups were analyzed.RESULTS The total effective rate of the observation group(94.00%)was significantly higher than that of the control group(80.00%)(χ2=3.998;P=0.046).The blood glucose indexes,total cholesterol levels,triglyceride levels,low-density lipoprotein cholesterol levels,high-sensitivity C-reactive protein levels,interleukin-1βlevels,tumor necrosis factor-αlevels,HMGB1 Levels,ESR,MIF levels,platelet aggregation rates,and plasma viscosity of the two groups decreased after treatment;however,high-density lipoprotein cholesterol and PON-1 Levels increased after treatment.After treatment,the blood glucose indexes;blood lipid indexes;inflammatory factors;HMGB1,PON-1,and MIF levels;ESR;platelet aggregation rate;and plasma viscosity of the observation group were better than those of the control group(P<0.05).After treatment,all patients in the observation group had higher ADL scores and lower NIHSS scores than those in the control group(P<0.05).CONCLUSION Sodium ozagrel with atorvastatin can reduce inflammatory reactions;regulate ESR and HMGB1,PON-1,and MIF levels;control blood glucose and lipid indexes;and alleviate nerve injury without increasing adverse effects of atorvastatin alone.展开更多
BACKGROUND： Estrogen is neuroprotective effects such as breast carcinoma, endometria but long-term estrogen treatment can induce side cancer, and stroke. However, phytoestrogen is neuroprotective without these side e...BACKGROUND： Estrogen is neuroprotective effects such as breast carcinoma, endometria but long-term estrogen treatment can induce side cancer, and stroke. However, phytoestrogen is neuroprotective without these side effects. OBJECTIVE： To study the effects of Ginsenoside Rgl on facial neurons and brain-derived neurotrophic factor （BDNF） expression in the facial nucleus in ovariectomized rats. DESIGN, TIME AND SETTING： The randomized, controlled animal experiments were performed at the Ultrasonic Institute, Second Affiliated Hospital, Chongqing Medical University, China, from September 2007 to September 2008. MATERIALS： Ginsenoside Rgl （Sigma, USA）, rabbit anti-rat BDNF, Bcl-2, Bax antibodies, biotin-labeled goat anti-rabbit IgG （Boster, China）, and a TUNEL kit （Roche, Germany） were used in this study. METHODS： A total of 48 adult Sprague Dawley rats undergoing ovariectomy were randomly assigned into sham operation （n = 8）, model （n = 20）, and Ginsenoside Rgl （n = 20） groups. Facial nerve damage was induced by bilateral clamping of the facial nerve trunk. The bilateral facial nerve trunk was exposed in the sham operation group, with no clamping. Rats in the Ginsenoside Rgl group were intraperitoneally injected with 10 mg/kg per day Ginsenoside Rgl; other groups received 2 mL saline, once a day, for 14 days. MAIN OUTCOME MEASURES： Morphologic changes in neurons of the facial nucleus were observed following hematoxylin-eosin staining. Neuronal apoptosis was detected by TUNEL. Changes in ultrastructure of the facial nerve fibers were observed with a transmission electron microscope. Expression of BDNF, Bcl-2, and Bax protein was quantified by semiquantitative immunohistochemistry. RESULTS： At 3-14 days following facial nerve damage, Ginsenoside Rgl increased BDNF expression and the number of regenerated nerve fibers, and produced thicker myelin sheaths （P 〈 0.05）. Ginsenoside Rgl also gradually increased Bcl-2 protein expression and decreased Bax protein expression （P 〈 0.05）. By day 7, apoptosis was observed in facial neurons, but Ginsenoside Rgl reduced the number of apoptotic neurons. Sham animals did not show any changes in BDNF, Bcl-2, or Bax expression or facial neuron morphology. CONCLUSION： Ginsenoside Rgl can substantially inhibit facial neuronal apoptosis by increasing endogenous BDNF and Bcl-2 expression and by decreasing Bax expression in ovariectomized rats after facial nerve damage.展开更多
Changes in mitochondrial morphology and function play an important role in secondary damage after acute spinal cord injury. We recorded the time representation of mitochondrial morphology and function in rats with acu...Changes in mitochondrial morphology and function play an important role in secondary damage after acute spinal cord injury. We recorded the time representation of mitochondrial morphology and function in rats with acute spinal cord injury. Results showed that mitochondria had an irregular shape, and increased in size. Mitochondrial cristae were disordered and mitochondrial membrane rupture was visible at 2–24 hours after injury. Fusion protein mitofusin 1 expression gradually increased, peaked at 8 hours after injury, and then decreased to its lowest level at 24 hours. Expression of dynamin-related protein 1, amitochondrial fission protein, showed the opposite kinetics. At 2–24 hours after acute spinal cord injury, malondialdehyde content, cytochrome c levels and caspase-3 expression were increased, but glutathione content, adenosine triphosphate content, Na＋-K＋-ATPase activity and mitochondrial membrane potential were gradually reduced. Furthermore, mitochondrial morphology altered during the acute stage of spinal cord injury. Fusion was important within the first 8 hours, but fission played a key role at 24 hours. Oxidative stress was inhibited, biological productivity was diminished, and mitochondrial membrane potential and permeability were reduced in the acute stage of injury. In summary, mitochondrial apoptosis is activated when the time of spinal cord injury is prolonged.展开更多
Objective:Leprosy is an infectious disease that can be accompanied by disability caused by peripheral neuropathy.Early detection of leprosy is essential to reduce its debilitating sequelae.Ultrasound is a noninvasive ...Objective:Leprosy is an infectious disease that can be accompanied by disability caused by peripheral neuropathy.Early detection of leprosy is essential to reduce its debilitating sequelae.Ultrasound is a noninvasive test that can detect nerve loss,but ultrasound measurement depends on the skill level of operators.Radiomics is an emerging field related to the extraction and quantification of information,which may provide new solutions for early detection of neuropathy caused by leprosy.This study aimed to combine radiomics and ultrasonography to evaluate nerve damage in the early stages of leprosy in China.Methods:Patients were enrolled at the Wenshan Prefecture Institute of Dermatology between October 2018 and December 2022.High-resolution ultrasound imaging of the peripheral nerves was performed.Quantitative ultrasound features were extracted from the images from 5 follow-ups.Radiomic features were selected for a comparative analysis of the disease course using a linear mixed-effects model to control for potential confounding effects.Results:Nine patients with leprosy were enrolled in this study,consisting of 5 males and 4 females with an average age of 34.44±13.58 years.With the change of treatment time,the ultrasound radiomics features of different parts of the linear mixed-effects model showed a trend of change:the nerve density(mean,skewness)was improved,the fascicular structure(kurtosis)was restored,and the abnormal morphological features in some parts were reduced(P<0.05).Patients with type 1 leprosy reactions exhibited a lower mean and skewness,higher kurtosis,and increased quantitative morphological characteristics.Conclusion:The study provided the feasibility of ultrasound radiomics to digitally visualize the progression of nerve damage in leprosy patients.Ultrasound radiomics can be a low-cost method with high-throughput characteristics for clinical operators of different skill levels in early nerve injury detection of leprosy.展开更多
文摘AIM:To investigate the effects of adenosine triphosphate(ATP)and melatonin,which have antioxidant and antiinflammatory activities,on potential 5-fluorouracil(5-FU)-induced optic nerve damage in rats.METHODS:Twenty-four rats were categorized into four groups of six rats:healthy(HG),5-FU(FUG),ATP+5-FU(AFU),and melatonin+5-FU(MFU).ATP(4 mg/kg)and melatonin(10 mg/kg)were administered intraperitoneally and orally,respectively.One hour after ATP and melatonin administration,rats in the AFU,MFU,and FUG were intraperitoneally injected with 5-FU(100 mg/kg).ATP and melatonin were administered once daily for 10d.5-FU was administered at a single dose on days 1,3,and 5 of the experiment.After 10d,the rats were euthanized and optic nerve tissues were extracted.Optic nerve tissues were biochemically and histopathologically examined.RESULTS:ATP and melatonin treatments inhibited the increase in malondialdehyde(MDA)and interleukin-6(IL-6)levels,which were elevated in the FUG.The treatments also prevented the decrease in total glutathione(tGSH)levels and the superoxide dismutase(SOD)and catalase(CAT)activities(P<0.001).This inhibition was higher in the ATP group than in the melatonin group(P<0.001).ATP prevented histopathological damage better than melatonin(P<0.05).CONCLUSION:ATP and melatonin have the potential to be used in alleviating 5-FU-induced optic nerve damage.In addition,ATP treatment shows better protective effects than melatonin.
基金Supported by National Nature Science Foundation of China (No.81070728)Shanghai "Science and Technology Innovation Action Plan" Basic Research Key Project,China (No.11JC1407700 and 11 JC1407701)+1 种基金Shanghai Nature Science Foundation, China (No.08ZR1413900)Shanghai Leading Academic Discipline Project, China(No.S30205)
文摘Rho-associated kinase (ROCK) is a serine/threonine kinase and one of the major downstream effectors of the small GTPase RhoA. The Rho/ROCK pathway is closely related to the pathogenesis of several central nervous system (CNS) disorders, and involved in many aspects of neuronal functions including neurite outgrowth and retraction. In the adult CNS, the damaged neuron regeneration is very difficult due to the presence of myelin-associated axon growth inhibitors such as Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte-myelin glycoprotein (Omgp), etc. The effects of these axon growth inhibitors are reversed by blocking the Rho/ROCK pathway 47 vitro, and the inhibition of Rho/ROCK pathway can promote axon regeneration and functional recovery in the injured CNS in viva In addition, the therapeutic effects of the Rho/ROCK inhibitors have also been demonstrated in some animal models and the Rho/ROCK pathway becomes an attractive target for the development of drugs for treating CNS disorders. In this review, we summarized on the effect of the Rho and the downstream factor ROCK in neural regeneration, and the potential therapeutic effect of Rho/ROCK inhibitors in the survival and axonal regeneration of retinal ganglion cell was also discussed.
基金supported by the National Key Research and Development Program of China,No.2019YFA0111200the National Natural Science Foundation of China,Nos.U23A20436,82371047+3 种基金Key Research Project in Shanxi Province,No.202302130501008Shanxi Provincial Science Fund for Distinguished Young Scholars,No.202103021221008Key Research and Development Program in Shanxi Province,No.202204051001023Shanxi Medical University Doctor’s Startup Fund Project,No.SD22028(all to YG)。
文摘Retinal ganglion cells are the bridging neurons between the eye and the central nervous system,transmitting visual signals to the brain.The injury and loss of retinal ganglion cells are the primary pathological changes in several retinal degenerative diseases,including glaucoma,ischemic optic neuropathy,diabetic neuropathy,and optic neuritis.In mammals,injured retinal ganglion cells lack regenerative capacity and undergo apoptotic cell death within a few days of injury.Additionally,these cells exhibit limited regenerative ability,ultimately contributing to vision impairment and potentially leading to blindness.Currently,the only effective clinical treatment for glaucoma is to prevent vision loss by lowering intraocular pressure through medications or surgery;however,this approach cannot halt the effect of retinal ganglion cell loss on visual function.This review comprehensively investigates the mechanisms underlying retinal ganglion cell degeneration in retinal degenerative diseases and further explores the current status and potential of cell replacement therapy for regenerating retinal ganglion cells.As our understanding of the complex processes involved in retinal ganglion cell degeneration deepens,we can explore new treatment strategies,such as cell transplantation,which may offer more effective ways to mitigate the effect of retinal degenerative diseases on vision.
基金supported by the National Natural Science Foundation of China, No. 81771140 (to YDZ)the Natural Science Foundation of Jiangsu Province of China, No. BK20201117 (to YDZ)Jiangsu “Six One Project” for Distinguished Medical Scholars of China, No. LGY2020013 (to TJ)
文摘Lamotrigine(LTG)is a widely used drug for the treatment of epilepsy.Emerging clinical evidence suggests that LTG may improve cognitive function in patients with Alzheimer’s disease.However,the underlying molecular mechanisms remain unclear.In this study,amyloid precursor protein/presenilin 1(APP/PS1)double transgenic mice were used as a model of Alzheimer’s disease.Five-month-old APP/PS1 mice were intragastrically administered 30 mg/kg LTG or vehicle once per day for 3 successive months.The cognitive functions of animals were assessed using Morris water maze.Hyperphosphorylated tau and markers of synapse and glial cells were detected by western blot assay.The cell damage in the brain was investigated using hematoxylin and eosin staining.The levels of amyloid-βand the concentrations of interleukin-1β,interleukin-6 and tumor necrosis factor-αin the brain were measured using enzyme-linked immunosorbent assay.Differentially expressed genes in the brain after LTG treatment were analyzed by high-throughput RNA sequencing and real-time polymerase chain reaction.We found that LTG substantially improved spatial cognitive deficits of APP/PS1 mice;alleviated damage to synapses and nerve cells in the brain;and reduced amyloid-βlevels,tau protein hyperphosphorylation,and inflammatory responses.High-throughput RNA sequencing revealed that the beneficial effects of LTG on Alzheimer’s disease-related neuropathologies may have been mediated by the regulation of Ptgds,Cd74,Map3k1,Fosb,and Spp1 expression in the brain.These findings revealed potential molecular mechanisms by which LTG treatment improved Alzheimer’s disease.Furthermore,these data indicate that LTG may be a promising therapeutic drug for Alzheimer’s disease.
文摘Organophosphate pesticide poisoning is an acute form of poisoning primarily found in underdeveloped regions.Its main clinical manifestations include muscarinic symptoms,nicotinic symptoms,and central nervous system disturbances.This report presents a case of a middleaged female who developed extremely rare symptoms of optic nerve damage after ingesting a large amount of an organophosphate pesticide.
基金Shanghai Municipal Natural Science Foundation,No.06ZR14108
文摘BACKGROUND： Schwann cells are the most commonly used cells for tissue-engineered nerves. However, autologous Schwann cells are of limited use in a clinical context, and allogeneic Schwann cells induce immunological rejections. Cells that do not induce immunological rejections and that are relatively easy to acquire are urgently needed for transplantation. OBJECTIVE： To bridge sciatic nerve defects using tissue engineered nerves constructed with neural tissue-committed stem cells （NTCSCs） derived from bone marrow; to observe morphology and function of rat nerves following bridging; to determine the effect of autologous nerve transplantation, which serves as the gold standard for evaluating efficacy of tissue-engineered nerves. DESIGN, TIME AND SETTING： This randomized, controlled, animal experiment was performed in the Anatomical Laboratory and Biomedical Institute of the Second Military Medical University of Chinese PLA between September 2004 and April 2006. MATERIALS： Five Sprague Dawley rats, aged 1 month and weighing 100-150 g, were used for cell culture. Sixty Sprague Dawley rats aged 3 months and weighing 220-250 g, were used to establish neurological defect models. Nestin, neuron-specific enolase （NSE）, glial fibrillary acidic protein （GFAP）, and S-100 antibodies were provided by Santa Cruz Biotechnology, Inc., USA. Acellular nerve grafts were derived from dogs. METHODS： All rats, each with 1-cm gap created in the right sciatic nerve, were randomly assigned to three groups. Each group comprised 20 rats. Autograft nerve transplantation group： the severed 1-cm length nerve segment was reverted, but with the two ends exchanged; the proximal segment was sutured to the distal sciatic nerve stump and the distal segment to the proximal stump. Blank nerve scaffold transplantation group： a 1-cm length acellular nerve graft was used to bridge the sciatic nerve gap. NTCSC engineered nerve transplantation group： a 1-cm length acellular nerve graft, in which NTCSCs were inoculated, was used to bridge the sciatic nerve gap. MAIN OUTCOME MEASURES： Following surgery, sciatic nerve functional index and electrophysiology functions were evaluated for nerve conduction function, including conduction latency, conduction velocity, and action potential peak. Horseradish peroxidase （HRP, 20%） was injected into the gastrocnemius muscle to retrogradely label the 1-4 and L5 nerve ganglions, as well as neurons in the anterior horn of the spinal cord, in the three groups. Positive expression of nestin, NSE, GFAP, and S-100 were determined using an immunofluorescence double-labeling method. RESULTS： NTCSCs differentiated into neuronal-like cells and glial-like cells within 12 weeks after NTCSC engineered nerve transplantation. HRP retrograde tracing displayed a large amount of HRP-labeled neurons in I-45 nerve ganglions, as well as the anterior horn of the spinal cord, in both the autograft nerve transplantation and the NTCSC engineered nerve transplantation groups. However, few HRP-labeled neurons were detected in the blank nerve scaffold transplantation group. Nerve bridges in the autograft nerve transplantation and NTCSC engineered nerve transplantation groups exhibited similar morphology to normal nerves. Neither fractures or broken nerve bridges nor neuromas were found after bridging the sciatic nerve gap with NTCSCs-inoculated acellular nerve graft, indicating repair. Conduction latency, action potential, and conduction velocity in the NTCSC engineered nerve transplantation group were identical to the autograft nerve transplantation group （P 〉 0.05）, but significantly different from the blank nerve scaffold transplantation group （P 〈 0.05）. CONCLUSION＂ NTCSC tissue-engineered nerves were able to repair injured nerves and facilitated restoration of nerve conduction function, similar to autograft nerve transplantation. ＂
文摘AIM:To investigate the effect of Bak Foong Pills(BFP) on the expression of β-amyloid(Aβ) in rats retina with optic nerve transaction,and its roles and possible mechanisms in protecting optic nerve damage.· METHODS:Seventy-two healthy,Sprague-Dawley,adult rats were randomly assigned to three groups:negative control group(control group),optic nerve transection group(model group) and BFP treatment group(BFP group,100μg/mL) followed by establishing optic nerve transection model.The expression of Aβ was measured at 48 hours by Western-blotting.Moreover,the expressions of Bcl-2,Bax and Caspase-3 mRNA were evaluated at 48 hours by reverse transcriptase polymerase chain reaction(RT-PCR).RESULTS:There were significant differences among the control,model and BFP groups in the expression of Aβ(all P <0.01).Aβ expression was significantly higher in the model and BFP groups than that in the control group(P < 0.01),with a more significant reduction in the BFP group than that in the model group(P <0.01).Moreover,there were also significant differences among the three groups in the expressions of Bcl-2/Bax(Bcl-2:anti-apoptotic;Bax:proapoptotic) and Caspase-3 mRNA(proapoptotic)(all P<0.01).Bcl-2/Bax ratio was significantly lower and Caspase-3 mRNA expression was significantly higher in the model and BFP groups than those in the control group(P <0.01),with a significant growing of Bcl-2/Bax and reduction of Caspase-3 in the BFP group than those in the model group(P<0.01).· CONCLUSION:BFP can down-regulate Aβ expression in retina and may inhibit apoptosis and protect optic nerve by enhancing Bcl-2/Bax ratio and inhibiting Caspase-3 pathway.
基金National Natural Science Foundation of China(No.81704123)Science and Technology Program of Guangzhou(No.2023A03J0774).
文摘Based on network pharmacology,this study predicted the potential molecular mechanism and related pathways of the protective effect of traditional Chuanxiong Rhizoma,a traditional Chinese herb,on glaucomatous optic nerve injury,and conducted in vitro experimental verification of the predicted results of network analysis.We analyzed the molecular mechanism of Chuanxiong Rhizoma in the potential treatment of glaucoma by revealing its main active ingredients and predicting its targets,so as to provide reference for subsequent basic research.Network pharmacological research results showed that the potential hub targets and key signaling pathways of Chuanxiong Rhizoma in the treatment of glaucoma were closely related to biological processes such as apoptosis,autophagy,inflammation,oxidative stress and angiogenesis.Molecular docking showed that many active ingredients,such as chrysophanol(CHR),myricanone and retinol,could combine well with their target proteins by intermolecular forces,especially CHR had strong binding ability with each target.We speculated that the main active component of Chuanxiong Rhizoma might be involved in the regulation of PI3K-Akt,Nod-like receptor,IL-4 and IL-13,MAPK,AGE-RAGE and neurotrophin signaling pathway by regulating of PI3K,Akt,TLR4,RAGE,NTRK2 and other key targets.Furthermore,it may achieve multi-directional intervention on apoptosis/autophagy,inflammation/immunity,oxidative stress and nutrient metabolism of axoplasma flow,and then delay the degeneration of optic nerve injury.In vitro experiments showed that the active component CHR of Chuanxiong Rhizoma could reverse the M1-type polarization and autophagy/apoptosis of mouse microglia(BV2)induced by lipopolysaccharide(LPS)at the transcriptional level.Meanwhile,the expression of inflammatory mediators IL-1βand TNF-αwas inhibited,and the mRNA level of anti-inflammatory factor IL-10 was significantly increased.In addition,CHR down-regulates activation of the RAGE-NOX4 pathway mediated by LPS in reducing oxidative stress.In this study,network pharmacology and molecular docking technology were integrated for the first time to explore the potential molecular mechanism of traditional Chinese herb“Chuanxiong Rhizoma”in the treatment on glaucoma,and CHR was innovatively proposed as an important ingredient in Chuanxiong Rhizoma that plays a protective role in the damage of optic nerve.Preliminary verification was conducted through in vitro experiments.The results suggest that Chuanxiong Rhizoma may interfere with autophagy and apoptosis,inhibit immune inflammation,as well as reduce oxidative stress in the treatment of glaucoma through the active components represented by CHR,so as to resist progressive optic nerve injury.Our study provides theoretical basis for the clinical use of Chinese herbal medicine or its extract in glaucoma,and also lays a solid foundation for the research of Chinese medicine in the field of optic nerve protection.
基金supported by the National Institutes of Health,USA(DE018549,UL1TR001117,P30AR066527,and AR48182 to WL,AR48182-S1 to WL as co-investigatorF33DE024668 and K12DE022793 to YC)+1 种基金the US Department of Defense(W81XWH-13-1-0299 to WL)the Harrington Discovery Institute,Cleveland OH(to WL)
文摘Nociception is an important physiological process that detects harmful signals and results in pain perception. In this review, we discuss important experimental evidence involving some TRP ion channels as molecular sensors of chemical, thermal, and mechanical noxious stimuli to evoke the pain and itch sensations. Among them are the TRPA1 channel, members of the vanilloid subfamily （TRPV1, TRPV3, and TRPV4）, and finally members of the melastatin group （TRPM2, TRPM3, and TRPMS）. Given that pain and itch are pro-survival, evolutionarily-honed protective mechanisms, care has to be exercised when developing inhibitory/modulatory com- pounds targeting specific pain/itch-TRPs so that physio- logical protective mechanisms are not disabled to a degree that stimulus-mediated injury can occur. Such events have impeded the development of safe and effective TRPV1- modulating compounds and have diverted substantial resources. A beneficial outcome can be readily accom- plished via simple dosing strategies, and also by incorpo- rating medicinal chemistry design features during compound design and synthesis. Beyond clinical use, where compounds that target more than one channel might have a place and possibly have advantageous features, highly specific and high-potency compounds will be helpful in mechanistic discovery at the structure-function level.
文摘BACKGROUND The main pathological factor of cerebral infarction is atherosclerosis,which is the pathological process of chronic inflammatory diseases such as vascular smooth muscle hyperplasia,inflammatory cell infiltration,extracellular matrix increase,and thrombosis.At present,the focus of clinical treatment is anti-platelet aggregation and improving blood status,and current research is limited to improving symptoms only.AIM To observe the effect of sodium ozagrel and atorvastatin on type 2 diabetes patients with lacunar cerebral infarction.METHODS Eighty-two patients with type 2 diabetes and lacunar cerebral infarction admitted to our hospital from January 2018 to February 2020 were equally categorized into two groups according to their treatment method.The control group was administered atorvastatin,and the observation group was administered sodium ozagrel combined with atorvastatin.The National Institutes of Health stroke scale(NIHSS)score,activities of daily living(ADL)score,blood glucose,lipid levels,inflammatory factors,high-mobility group box 1(HMGB1)levels,paraoxonase-1(PON-1)levels,erythrocyte sedimentation rate(ESR),and macrophage migration inhibitory factor(MIF)levels were recorded before and after treatment.The total effective rate and adverse reaction rate of the two groups were analyzed.RESULTS The total effective rate of the observation group(94.00%)was significantly higher than that of the control group(80.00%)(χ2=3.998;P=0.046).The blood glucose indexes,total cholesterol levels,triglyceride levels,low-density lipoprotein cholesterol levels,high-sensitivity C-reactive protein levels,interleukin-1βlevels,tumor necrosis factor-αlevels,HMGB1 Levels,ESR,MIF levels,platelet aggregation rates,and plasma viscosity of the two groups decreased after treatment;however,high-density lipoprotein cholesterol and PON-1 Levels increased after treatment.After treatment,the blood glucose indexes;blood lipid indexes;inflammatory factors;HMGB1,PON-1,and MIF levels;ESR;platelet aggregation rate;and plasma viscosity of the observation group were better than those of the control group(P<0.05).After treatment,all patients in the observation group had higher ADL scores and lower NIHSS scores than those in the control group(P<0.05).CONCLUSION Sodium ozagrel with atorvastatin can reduce inflammatory reactions;regulate ESR and HMGB1,PON-1,and MIF levels;control blood glucose and lipid indexes;and alleviate nerve injury without increasing adverse effects of atorvastatin alone.
文摘BACKGROUND： Estrogen is neuroprotective effects such as breast carcinoma, endometria but long-term estrogen treatment can induce side cancer, and stroke. However, phytoestrogen is neuroprotective without these side effects. OBJECTIVE： To study the effects of Ginsenoside Rgl on facial neurons and brain-derived neurotrophic factor （BDNF） expression in the facial nucleus in ovariectomized rats. DESIGN, TIME AND SETTING： The randomized, controlled animal experiments were performed at the Ultrasonic Institute, Second Affiliated Hospital, Chongqing Medical University, China, from September 2007 to September 2008. MATERIALS： Ginsenoside Rgl （Sigma, USA）, rabbit anti-rat BDNF, Bcl-2, Bax antibodies, biotin-labeled goat anti-rabbit IgG （Boster, China）, and a TUNEL kit （Roche, Germany） were used in this study. METHODS： A total of 48 adult Sprague Dawley rats undergoing ovariectomy were randomly assigned into sham operation （n = 8）, model （n = 20）, and Ginsenoside Rgl （n = 20） groups. Facial nerve damage was induced by bilateral clamping of the facial nerve trunk. The bilateral facial nerve trunk was exposed in the sham operation group, with no clamping. Rats in the Ginsenoside Rgl group were intraperitoneally injected with 10 mg/kg per day Ginsenoside Rgl; other groups received 2 mL saline, once a day, for 14 days. MAIN OUTCOME MEASURES： Morphologic changes in neurons of the facial nucleus were observed following hematoxylin-eosin staining. Neuronal apoptosis was detected by TUNEL. Changes in ultrastructure of the facial nerve fibers were observed with a transmission electron microscope. Expression of BDNF, Bcl-2, and Bax protein was quantified by semiquantitative immunohistochemistry. RESULTS： At 3-14 days following facial nerve damage, Ginsenoside Rgl increased BDNF expression and the number of regenerated nerve fibers, and produced thicker myelin sheaths （P 〈 0.05）. Ginsenoside Rgl also gradually increased Bcl-2 protein expression and decreased Bax protein expression （P 〈 0.05）. By day 7, apoptosis was observed in facial neurons, but Ginsenoside Rgl reduced the number of apoptotic neurons. Sham animals did not show any changes in BDNF, Bcl-2, or Bax expression or facial neuron morphology. CONCLUSION： Ginsenoside Rgl can substantially inhibit facial neuronal apoptosis by increasing endogenous BDNF and Bcl-2 expression and by decreasing Bax expression in ovariectomized rats after facial nerve damage.
基金supported by the National Natural Science Foundation of China,No.81272074the Scientific Research Foundation Project for Doctors in Liaoning Province of China,No.20121094+1 种基金Aohongboze Graduate Sci-tech Innovation Foundationthe President Fund of Liaoning Medical University of China,No.2013003
文摘Changes in mitochondrial morphology and function play an important role in secondary damage after acute spinal cord injury. We recorded the time representation of mitochondrial morphology and function in rats with acute spinal cord injury. Results showed that mitochondria had an irregular shape, and increased in size. Mitochondrial cristae were disordered and mitochondrial membrane rupture was visible at 2–24 hours after injury. Fusion protein mitofusin 1 expression gradually increased, peaked at 8 hours after injury, and then decreased to its lowest level at 24 hours. Expression of dynamin-related protein 1, amitochondrial fission protein, showed the opposite kinetics. At 2–24 hours after acute spinal cord injury, malondialdehyde content, cytochrome c levels and caspase-3 expression were increased, but glutathione content, adenosine triphosphate content, Na＋-K＋-ATPase activity and mitochondrial membrane potential were gradually reduced. Furthermore, mitochondrial morphology altered during the acute stage of spinal cord injury. Fusion was important within the first 8 hours, but fission played a key role at 24 hours. Oxidative stress was inhibited, biological productivity was diminished, and mitochondrial membrane potential and permeability were reduced in the acute stage of injury. In summary, mitochondrial apoptosis is activated when the time of spinal cord injury is prolonged.
文摘Objective:Leprosy is an infectious disease that can be accompanied by disability caused by peripheral neuropathy.Early detection of leprosy is essential to reduce its debilitating sequelae.Ultrasound is a noninvasive test that can detect nerve loss,but ultrasound measurement depends on the skill level of operators.Radiomics is an emerging field related to the extraction and quantification of information,which may provide new solutions for early detection of neuropathy caused by leprosy.This study aimed to combine radiomics and ultrasonography to evaluate nerve damage in the early stages of leprosy in China.Methods:Patients were enrolled at the Wenshan Prefecture Institute of Dermatology between October 2018 and December 2022.High-resolution ultrasound imaging of the peripheral nerves was performed.Quantitative ultrasound features were extracted from the images from 5 follow-ups.Radiomic features were selected for a comparative analysis of the disease course using a linear mixed-effects model to control for potential confounding effects.Results:Nine patients with leprosy were enrolled in this study,consisting of 5 males and 4 females with an average age of 34.44±13.58 years.With the change of treatment time,the ultrasound radiomics features of different parts of the linear mixed-effects model showed a trend of change:the nerve density(mean,skewness)was improved,the fascicular structure(kurtosis)was restored,and the abnormal morphological features in some parts were reduced(P<0.05).Patients with type 1 leprosy reactions exhibited a lower mean and skewness,higher kurtosis,and increased quantitative morphological characteristics.Conclusion:The study provided the feasibility of ultrasound radiomics to digitally visualize the progression of nerve damage in leprosy patients.Ultrasound radiomics can be a low-cost method with high-throughput characteristics for clinical operators of different skill levels in early nerve injury detection of leprosy.
