The combination of Daphnes Cortex(DC)and Liquorice Root(LR),two traditional Chinese medicinal herbs,has shown significant therapeutic effects on rheumatoid arthritis(RA),but its synergistic mechanism of action remains...The combination of Daphnes Cortex(DC)and Liquorice Root(LR),two traditional Chinese medicinal herbs,has shown significant therapeutic effects on rheumatoid arthritis(RA),but its synergistic mechanism of action remains to be elucidated.Employing a network pharmacology and molecular docking approach,this study systematically investigated the synergistic mechanism of the herb pair DC and LR in RA treatment.Active components and their corresponding targets were retrieved from the TCMSP database and relevant literature,and RA-related targets were collected from established disease databases.A total of 73 overlapping targets between DC-LR and RA were identified,among which core targets such as AKT1,TNF,and CASP3 were highlighted.GO and KEGG enrichment analyses revealed that these targets are involved in biological processes such as oxidative stress response and cell migration,and are significantly enriched in key pathways including HIF-1,TNF,and PI3K-Akt signaling pathways.Compatibility analysis further revealed that the combination of DC and LR may enhance therapeutic effects through synergistic regulation of shared targets and complementary modulation of upstream and downstream pathway components.Molecular docking confirmed strong binding affinities between core active components and key targets.This study provides a multi-dimensional“component-target-pathway”perspective on the potential synergistic anti-RA mechanism of the DC-LR herb pair,offering a theoretical basis for further experimental validation and clinical application.展开更多
Moutan Cortex terpene glycoside is derived from the dried root bark of Paeonia suffruticosa Andr.in the Paeoniaceae family,which holds significant value as a traditional Chinese medicine.This study investigated that M...Moutan Cortex terpene glycoside is derived from the dried root bark of Paeonia suffruticosa Andr.in the Paeoniaceae family,which holds significant value as a traditional Chinese medicine.This study investigated that Moutan Cortex terpene glycoside(MCTG)improved diabetic kidney disease(DKD)by targeting sirtuin 1(SIRT1)mediated autophagy pathway.Mechanistic insights were gained using DKD model rats and human umbilical vein endothelial cells(HUVECs)to delineate how MCTG operated in the treatment of DKD.Furthermore,network pharmacology was used to identify the primary metabolic pathways affected by MCTG,with key targets being confirmed through polymerase chain reaction(PCR),Western blot,Transmission electron microscope,immunofluorescence staining and monodansylcadaverine(MDC)staining.Finally,small interfering RNA transfection testified SIRT1 in advanced glycation end-products(AGEs)-induced HUVECs injury.MCTG effectively decreased blood glucose rise in DKD rats and reduced levels of cytokines and biochemical indicators.Network pharmacology revealed that metabolism was the main pathway of Moutan Cortex,and the main targets were verified by PCR and protein experiments.Based on these results,we found that Moutan Cortex could improve DKD and SIRT1 was a potential target.Furthermore,knockdown of SIRT1 attenuated AGEs-induced the expression of Beclin 1 and microtubule-associated protein 1 light chain 3 II/I(LC3 II/I)in HUVECs.In summary,this study demonstrated that Moutan Cortex could alleviate DKD via down-regulating SIRT1-mediated autophagy pathway.展开更多
Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglio...Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglion cells and their axons,leading to axonal transport dysfuntion,subsequently causing secondary damage to anterior or posterior ends of the visual system.Accordingly,recent evidence indicates that glaucoma is a degenerative disease of the central nervous system that causes damage throughout the visual pathway.However,the effects of glaucoma on synaptic plasticity in the primary visual cortex remain unclear.In this study,we established a mouse model of unilateral chronic ocular hypertension by injecting magnetic microbeads into the anterior chamber of one eye.We found that,after 4 weeks of chronic ocular hypertension,the neuronal somas were smaller in the superior colliculus and lateral geniculate body regions of the brain contralateral to the affected eye.This was accompanied by glial cell activation and increased expression of inflammatory factors.After 8 weeks of ocular hypertension,we observed a reduction in the number of excitatory and inhibitory synapses,dendritic spines,and activation of glial cells in the primary visual cortex contralateral to the affected eye.These findings suggest that glaucoma not only directly damages the retina but also induces alterations in synapses and dendritic spines in the primary visual cortex,providing new insights into the pathogenesis of glaucoma.展开更多
Objective:To anatomically and phenotypically characterize the insular cortex(IC)-nucleus tractus soli-tari(NTS)neural pathway.Methods:Adult male Sprague-Dawley rats were divided into three experimental cohorts for neu...Objective:To anatomically and phenotypically characterize the insular cortex(IC)-nucleus tractus soli-tari(NTS)neural pathway.Methods:Adult male Sprague-Dawley rats were divided into three experimental cohorts for neural circuit tracing.Anterograde labeling was achieved by injecting anterograde self-complementary adeno-associated viruses(scAAVs)into the IC.Retrograde tracing involved NTS injections of either retrograde scAAVs or FluoroGold(FG),combined with immunofluorescence histochemical staining to identify IC-originating projection neurons.For postsynaptic neurochemical phenotype characterization,IC was injected with AAV2/1-CaMKII-Cre,while a mixture of AAV2/9-Syn-DIO-mCherry and AAV2/9-VGAT1-EGFP was injected into the NTS.The rats were allowed to survive for one week following scAAVs or FG injection or four weeks after recombinase-dependent systems injection.Then the rats were sacrificed,and serial brain sections were prepared for immunofluorescence histochemical staining(brain section containing FG)and subsequent fluorescence/confocal microscopic analysis.Results:(1)Anterograde viral tracing re-vealed dense axonal terminals from the IC projecting to the medial subnucleus of the NTS,while retrograde tracing re-vealed that IC neurons projecting to the NTS were predominantly localized within the dysgranular layer;(2)IC-NTS projection neurons were exclusive glutamatergic(100%,n=3);(3)NTS neurons receiving IC inputs were mainly lo-calized in the medial subnucleus,and were predominantly GABAergic(79.8±3.2%,n=3).Conclusion:The pres-ent results indicate that a descending pathway from excitatory neurons of the IC terminates onto inhibitory neurons of the NTS,which might represent a potential neuromodulatory target for visceral pain disorders.展开更多
Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairme...Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.展开更多
The visual cortex is an essential part of the brain for processing visual information.It exhibits structural and functional plasticity,which is crucial for adapting to complex visual environments.The quintessential ma...The visual cortex is an essential part of the brain for processing visual information.It exhibits structural and functional plasticity,which is crucial for adapting to complex visual environments.The quintessential manifestation of visual cortical plasticity is ocular dominance plasticity during the critical period,which involves numerous cellular and molecular events.While previous studies have emphasized the role of visual cortical neurons and their associated functional molecules in visual plasticity,recent findings have revealed that structural factors such as the extracellular matrix and glia are also involved.Investigating how these molecules interact to form a complex network that facilitates plasticity in the visual cortex is crucial to our understanding of the development of the visual system and the advancement of therapeutic strategies for visual disorders like amblyopia.展开更多
Lycii Radicis Cortex(LRC)is a medicinal and food homologous plant with various pharmacological activities,including anti-tumor effects.This study explores the anti-tumor effect of LRC on non-small cell lung cancer(NSC...Lycii Radicis Cortex(LRC)is a medicinal and food homologous plant with various pharmacological activities,including anti-tumor effects.This study explores the anti-tumor effect of LRC on non-small cell lung cancer(NSCLC)and its molecular mechanism using mice bearing Lewis lung carcinoma cells.LRC significantly suppressed the growth of NSCLC.Besides,RNA sequencing of mice tumors and hematoxylin&eosin and immunofluorescence staining revealed that LRC promoted the infiltration of T lymphocytes,specifically GZMB~+CD8~+T lymphocytes,in tumor tissues.The Gene Set Enrichment Analysis of spleen RNA indicated that LRC up-regulated PD-1-downstream pathways,suggesting that LRC exerted its effects through the PDL1/PD-1 pathway.Further experiments revealed that LRC interacted with PD-L1,blocking PD-L1/PD-1 binding and thus restoring the T cell killing activity on tumor cells.Together,these results support using LRC as healthy food to improve anti-tumor immunity in patients with NSCLC.展开更多
The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate ne...The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.展开更多
Dear Editor,The importance of the medial entorhinal cortex(MEC)for memory and spatial navigation has been shown repeatedly in many species,including mice and humans[1,2].It is,therefore,not surprising that the connect...Dear Editor,The importance of the medial entorhinal cortex(MEC)for memory and spatial navigation has been shown repeatedly in many species,including mice and humans[1,2].It is,therefore,not surprising that the connectivity of this structure has been studied extensively over the past century,mainly using a range of anterograde and retrograde anatomical tracers[3].展开更多
Spinal cord injury typically causes corticospinal tract disruption.Although the disrupted corticospinal tract can self-regenerate to a certain degree,the underlying mechanism of this process is still unclear.N6-methyl...Spinal cord injury typically causes corticospinal tract disruption.Although the disrupted corticospinal tract can self-regenerate to a certain degree,the underlying mechanism of this process is still unclear.N6-methyladenosine(m^(6)A)modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes.However,whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown.We found that expression of methyltransferase 14 protein(METTL14)in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels.Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury.Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction,we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner,thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration.Finally,we administered syringin,a stabilizer of METTL14,using molecular docking.Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14.Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.展开更多
[Objectives]This study was conducted to investigate the alleviating effect of Phellodendri Chinensis Cortex extract on the phytotoxicity of pretilachlor in rice.[Methods]In addition to CK,Phellodendri Chinensis Cortex...[Objectives]This study was conducted to investigate the alleviating effect of Phellodendri Chinensis Cortex extract on the phytotoxicity of pretilachlor in rice.[Methods]In addition to CK,Phellodendri Chinensis Cortex extract and pretilachlor with different gradients were added to the culture medium,and rice seeds with the same bud length were evenly placed in the culture medium.After 10 and 15 d of culture,the plant height and fresh weight of rice seedlings were measured and the alleviation rate was calculated.[Results]Ten days after application,the plant height of treatment 8(pretilachlor:extract concentration ratio of 25:200)was alleviated with an alleviation rate of 21.72%,and the fresh weight of treatment 9(pretilachlor:extract concentration ratio of 25:400)was alleviated with an alleviation rate of 31.04%.Fifteen days after treatment,the plant height of treatment 6(pretilachlor:extract concentration ratio of 25:50)showed a better alleviating effect,and the fresh weight of treatment 8(pretilachlor:extract concentration ratio of 25:200)exhibited a better alleviating effect,with an alleviation rate of 22.39%.Meanwhile,it was found that the extract of Phellodendri Chinensis Cortex could alleviate the increase of POD activity in rice leaves caused by pretilachlor.Meanwhile,it was found that the extract of Phellodendri Chinensis Cortex promoted the expression of CAT in rice seedlings,thus significantly increasing its activity and alleviating the toxicity of pretilachlor to rice.[Conclusions]This study can provide technical support for the screening and field application of plant-derived safeners.展开更多
The anterior cingulate cortex(ACC)has recently been proposed as a key player in the representation of itch stimuli.However,to date,little is known about the contribution of specific ACC interneuron populations to itch...The anterior cingulate cortex(ACC)has recently been proposed as a key player in the representation of itch stimuli.However,to date,little is known about the contribution of specific ACC interneuron populations to itch processing.Using c-Fos immunolabeling and in vivo Ca2+imaging,we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide(VIP)-expressing interneuron activity in the ACC.Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch.Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis.Together,this study highlights the importance of ACC VIP+neurons in modulating itch-related affect and behavior,which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.展开更多
Objective:To elucidate the specific mechanisms by which electroacupuncture(EA)alleviates anxiety and fear behaviors associated with posttraumatic stress disorder(PTSD),focusing on the role of lipocalin-2(Lcn2).Methods...Objective:To elucidate the specific mechanisms by which electroacupuncture(EA)alleviates anxiety and fear behaviors associated with posttraumatic stress disorder(PTSD),focusing on the role of lipocalin-2(Lcn2).Methods:The PTSD mouse model was subjected to single prolonged stress and shock(SPS&S),and the animals received 15 min sessions of EA at Shenmen acupoint(HT7).Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear.Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex(PFC).Additionally,the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology.Results:Mice subjected to SPS&S presented increased anxiety-and fear-like behaviors.Lcn2 expression in the PFC was significantly upregulated following SPS&S,leading to increased expression of the proinflammatory cytokines tumor necrosis factor-a and interleukin-6 and suppression of PFC neuronal activity.However,EA at HT7 inhibited Lcn2 release,reducing neuroinflammation and hypoexcitability in the PFC.Lcn2 overexpression mitigated the effects of EA at HT7,resulting in anxiety-and fear-like behaviors.Conclusion:EA at HT7 can ameliorate PTSD-associated anxiety and fear,and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC.展开更多
AIM:To investigate the postnatal development of parvalbumin(PV)-positive gamma-aminobutyric acid(GABA)interneurons and the co-expression of perineuronal nets(PNNs)and PV in the visual cortex of rats,as well as the reg...AIM:To investigate the postnatal development of parvalbumin(PV)-positive gamma-aminobutyric acid(GABA)interneurons and the co-expression of perineuronal nets(PNNs)and PV in the visual cortex of rats,as well as the regulatory effects of fluoxetine(FLX)treatment and binocular form deprivation(BFD)on these indices.METHODS:Wistar rats were assigned to three experimental cohorts:1)Age-related groups:postnatal week(PW)1,PW3,PW5,PW7,and PW9;2)FLX treatment duration groups:FLX 0W,FLX 2W,FLX 4W,FLX 6W,and FLX 8W;3)Intervention groups:control(Cont),FLX,BFD,and BFD+FLX.The levels of PNNs,PV,and PNNs/PV coexpression in the visual cortex were detected and analyzed.RESULTS:The density of PV-positive cells and the coexpression of PNNs and PV increased gradually with the maturation of the visual cortex(b=0.960,P<0.01).The ratio of PV-positive cells surrounded by PNNs to total PV-positive cells(PNNs+/PV+/total PV+)was significantly decreased in the FLX 4W group(χ^(2)=9.03,P=0.003).There was no significant difference in the PNNs+/PV+/total PV+ratio between the FLX and BFD groups(χ^(2)=1.08,P=0.161),but a significant difference was observed between the BFD+FLX group and the BFD group(χ^(2)=5.82,P<0.01).CONCLUSION:The number of PV-positive neurons and PNNs-surrounded PV neurons in the rat visual cortex increases postnatally and reaches adult levels by postnatal week 7.Chronic FLX treatment downregulates these expressions.Combined 4-week FLX treatment and BFD exerts a more significant inhibitory effect on the PNNs+/PV+/total PV+ratio than either intervention alone.展开更多
To determine the addition amount of Phellodendri Chinensis Cortex residue for composting,this study designed four Phellodendri Chinensis Cortex residue treatments of 100(A1),150(A2),200(A3),and 250(A4).Then,mushroom s...To determine the addition amount of Phellodendri Chinensis Cortex residue for composting,this study designed four Phellodendri Chinensis Cortex residue treatments of 100(A1),150(A2),200(A3),and 250(A4).Then,mushroom substrate residue,rice husks,and pig manure were added,and the cellulose-degrading strain ZG2-3 was inoculated at 5%for composting.The inoculation of a commercially available microbial agent was taken as the positive control(PC),and no inoculation of microbial agent as the blank control(CK).The effect of different treatments on the heavy metal content,nutrients,physicochemical properties,and microbial counts of compost and the seed germination index(GI)were studied and compared.The results showed that except that in CK,the content of heavy metals in other treatments did not exceed the standard limits.With the increase in the addition amount of Phellodendri Chinensis Cortex residue,the content of available nitrogen,available phosphorus,available potassium,and total nutrients in the compost also increased.Adding microbial agent significantly increased the content of total nutrients,available nitrogen,available phosphorus,available potassium,total nitrogen,total phosphorus,and total potassium in the compost,while reducing the content of organic matter.The GI was the highest in A4 treatment,reaching 85.33%,and it followed a trend of A3>PC>CK.This indicated that the inoculation of microbial agent accelerated the maturation of compost,and ZG2-3 outperformed the commercially available Bacillus subtilis.Overall,the A4 treatment(250 g Phellodendri Chinensis Cortex residue+125 g mushroom substrate residue+125 g rice husks+1000 g pig manure+inoculation of 5%ZG2-3)performed well in terms of nutrients content,physicochemical properties,and GI and had good safety,being the optimal formula for composting.展开更多
Anxiety disorder is a major symptom of autism spectrum disorder(ASD)with a comorbidity rate of~40%.However,the neural mechanisms of the emergence of anxiety in ASD remain unclear.In our study,we found that hyperactivi...Anxiety disorder is a major symptom of autism spectrum disorder(ASD)with a comorbidity rate of~40%.However,the neural mechanisms of the emergence of anxiety in ASD remain unclear.In our study,we found that hyperactivity of basolateral amygdala(BLA)pyramidal neurons(PNs)in Shank3 InsG3680 knock-in(InsG3680+/+)mice is involved in the development of anxiety.Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs.Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680+/+mice.Further study found that the diminished control of the BLA by medial prefrontal cortex(mPFC)and optogenetic activation of the mPFC-BLA pathway also had a rescue effect,which increased the feedforward inhibition of the BLA.Taken together,our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680+/+mice.展开更多
Schizophrenia is a multifaceted neurodevelopmental disorder characterized by hallucinations,delusions,cognitive deficits,and emotional dysregulation.The prefrontal cortex(PFC),essential for executive functions,working...Schizophrenia is a multifaceted neurodevelopmental disorder characterized by hallucinations,delusions,cognitive deficits,and emotional dysregulation.The prefrontal cortex(PFC),essential for executive functions,working memory,and emotional regulation,is notably impaired in this condition.This review consolidates current insights into the role of PFC dysfunction in schizophrenia,with a focus on its implications for therapeutic strategies.The neuroanatomical and neurobiological foundations of PFC dysfunction are explored,emphasizing structural abnormalities,functional dysconnectivity,and microcircuit disruptions that contribute to cognitive deficits and impaired decision-making.Clinical implications are discussed,particularly the correlation between PFC dysfunction and the severity and progression of schizophrenia symptoms.Additionally,pharmacological and non-pharmacological approaches aimed at modulating PFC activity are reviewed as potential therapeutic options.In conclusion,a deeper understanding of PFC dysfunction is pivotal for developing targeted treatments,and ongoing research offers promising avenues for enhancing outcomes for individuals affected by this debilitating disorder.展开更多
基金supported by National Training Program of Innovation and Entrepreneurship for Undergraduates(202510163044).
文摘The combination of Daphnes Cortex(DC)and Liquorice Root(LR),two traditional Chinese medicinal herbs,has shown significant therapeutic effects on rheumatoid arthritis(RA),but its synergistic mechanism of action remains to be elucidated.Employing a network pharmacology and molecular docking approach,this study systematically investigated the synergistic mechanism of the herb pair DC and LR in RA treatment.Active components and their corresponding targets were retrieved from the TCMSP database and relevant literature,and RA-related targets were collected from established disease databases.A total of 73 overlapping targets between DC-LR and RA were identified,among which core targets such as AKT1,TNF,and CASP3 were highlighted.GO and KEGG enrichment analyses revealed that these targets are involved in biological processes such as oxidative stress response and cell migration,and are significantly enriched in key pathways including HIF-1,TNF,and PI3K-Akt signaling pathways.Compatibility analysis further revealed that the combination of DC and LR may enhance therapeutic effects through synergistic regulation of shared targets and complementary modulation of upstream and downstream pathway components.Molecular docking confirmed strong binding affinities between core active components and key targets.This study provides a multi-dimensional“component-target-pathway”perspective on the potential synergistic anti-RA mechanism of the DC-LR herb pair,offering a theoretical basis for further experimental validation and clinical application.
基金supported by grants from the National Natural Science Foundation of China(82474093,81973536)Jiangsu Province“Blue and Green Project”(184080H10240)+2 种基金Graduate Research Innovation Program of Jiangsu(KYCX23_0871)the National Natural Science Foundation of the Youth Science Fund Project(81703775)Health Research Program of Wuxi Municipal Health Commission(Q202107).
文摘Moutan Cortex terpene glycoside is derived from the dried root bark of Paeonia suffruticosa Andr.in the Paeoniaceae family,which holds significant value as a traditional Chinese medicine.This study investigated that Moutan Cortex terpene glycoside(MCTG)improved diabetic kidney disease(DKD)by targeting sirtuin 1(SIRT1)mediated autophagy pathway.Mechanistic insights were gained using DKD model rats and human umbilical vein endothelial cells(HUVECs)to delineate how MCTG operated in the treatment of DKD.Furthermore,network pharmacology was used to identify the primary metabolic pathways affected by MCTG,with key targets being confirmed through polymerase chain reaction(PCR),Western blot,Transmission electron microscope,immunofluorescence staining and monodansylcadaverine(MDC)staining.Finally,small interfering RNA transfection testified SIRT1 in advanced glycation end-products(AGEs)-induced HUVECs injury.MCTG effectively decreased blood glucose rise in DKD rats and reduced levels of cytokines and biochemical indicators.Network pharmacology revealed that metabolism was the main pathway of Moutan Cortex,and the main targets were verified by PCR and protein experiments.Based on these results,we found that Moutan Cortex could improve DKD and SIRT1 was a potential target.Furthermore,knockdown of SIRT1 attenuated AGEs-induced the expression of Beclin 1 and microtubule-associated protein 1 light chain 3 II/I(LC3 II/I)in HUVECs.In summary,this study demonstrated that Moutan Cortex could alleviate DKD via down-regulating SIRT1-mediated autophagy pathway.
基金supported by the National Natural Science Foundation of China,No.82271115(to MY).
文摘Synaptic plasticity is essential for maintaining neuronal function in the central nervous system and serves as a critical indicator of the effects of neurodegenerative disease.Glaucoma directly impairs retinal ganglion cells and their axons,leading to axonal transport dysfuntion,subsequently causing secondary damage to anterior or posterior ends of the visual system.Accordingly,recent evidence indicates that glaucoma is a degenerative disease of the central nervous system that causes damage throughout the visual pathway.However,the effects of glaucoma on synaptic plasticity in the primary visual cortex remain unclear.In this study,we established a mouse model of unilateral chronic ocular hypertension by injecting magnetic microbeads into the anterior chamber of one eye.We found that,after 4 weeks of chronic ocular hypertension,the neuronal somas were smaller in the superior colliculus and lateral geniculate body regions of the brain contralateral to the affected eye.This was accompanied by glial cell activation and increased expression of inflammatory factors.After 8 weeks of ocular hypertension,we observed a reduction in the number of excitatory and inhibitory synapses,dendritic spines,and activation of glial cells in the primary visual cortex contralateral to the affected eye.These findings suggest that glaucoma not only directly damages the retina but also induces alterations in synapses and dendritic spines in the primary visual cortex,providing new insights into the pathogenesis of glaucoma.
文摘Objective:To anatomically and phenotypically characterize the insular cortex(IC)-nucleus tractus soli-tari(NTS)neural pathway.Methods:Adult male Sprague-Dawley rats were divided into three experimental cohorts for neural circuit tracing.Anterograde labeling was achieved by injecting anterograde self-complementary adeno-associated viruses(scAAVs)into the IC.Retrograde tracing involved NTS injections of either retrograde scAAVs or FluoroGold(FG),combined with immunofluorescence histochemical staining to identify IC-originating projection neurons.For postsynaptic neurochemical phenotype characterization,IC was injected with AAV2/1-CaMKII-Cre,while a mixture of AAV2/9-Syn-DIO-mCherry and AAV2/9-VGAT1-EGFP was injected into the NTS.The rats were allowed to survive for one week following scAAVs or FG injection or four weeks after recombinase-dependent systems injection.Then the rats were sacrificed,and serial brain sections were prepared for immunofluorescence histochemical staining(brain section containing FG)and subsequent fluorescence/confocal microscopic analysis.Results:(1)Anterograde viral tracing re-vealed dense axonal terminals from the IC projecting to the medial subnucleus of the NTS,while retrograde tracing re-vealed that IC neurons projecting to the NTS were predominantly localized within the dysgranular layer;(2)IC-NTS projection neurons were exclusive glutamatergic(100%,n=3);(3)NTS neurons receiving IC inputs were mainly lo-calized in the medial subnucleus,and were predominantly GABAergic(79.8±3.2%,n=3).Conclusion:The pres-ent results indicate that a descending pathway from excitatory neurons of the IC terminates onto inhibitory neurons of the NTS,which might represent a potential neuromodulatory target for visceral pain disorders.
基金supported by the National Natural Science Foundation of China,Nos.82374561(to JD),82174490(to JF)the Medical and Health Science and Technology Program of Zhejiang Province,No.2021RC098(to JD)the Research Project of Zhejiang Chinese Medical University,Nos.2022JKZKTS44(to JD),2022FSYYZZ07(to JF).
文摘Pain is often comorbid with emotional disorders such as anxiety and depression.Hyperexcitability of the anterior cingulate cortex has been implicated in pain and pain-related negative emotions that arise from impairments in inhibitory gamma-aminobutyric acid neurotransmission.This review primarily aims to outline the main circuitry(including the input and output connectivity)of the anterior cingulate cortex and classification and functions of different gamma-aminobutyric acidergic neurons;it also describes the neurotransmitters/neuromodulators affecting these neurons,their intercommunication with other neurons,and their importance in mental comorbidities associated with chronic pain disorders.Improving understanding on their role in pain-related mental comorbidities may facilitate the development of more effective treatments for these conditions.However,the mechanisms that regulate gamma-aminobutyric acidergic systems remain elusive.It is also unclear as to whether the mechanisms are presynaptic or postsynaptic.Further exploration of the complexities of this system may reveal new pathways for research and drug development.
基金supported by the National Natural Science Foundation of China(81770956,81371049,32471055 and 82171090)Project of Tianjin 131 Innovative Talent Team(201936)+4 种基金the Science and Technology Planning Project of Tianjin(21JCYBJC00780)the Science and Technology Fund for Health of Tianjin(TJWJ2023ZD008)Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)ZJLab,Shanghai Center for Brain Science and Brain-Inspired Technology,the Lingang Laboratory(LG-QS-202203-12)Tianjin Key Medical Discipline(Specialty)Construction Project(TJYXZDXK‑016A).
文摘The visual cortex is an essential part of the brain for processing visual information.It exhibits structural and functional plasticity,which is crucial for adapting to complex visual environments.The quintessential manifestation of visual cortical plasticity is ocular dominance plasticity during the critical period,which involves numerous cellular and molecular events.While previous studies have emphasized the role of visual cortical neurons and their associated functional molecules in visual plasticity,recent findings have revealed that structural factors such as the extracellular matrix and glia are also involved.Investigating how these molecules interact to form a complex network that facilitates plasticity in the visual cortex is crucial to our understanding of the development of the visual system and the advancement of therapeutic strategies for visual disorders like amblyopia.
基金supported by Natural Science Foundation of Guangdong Province,China(2022A1515011575)National Natural Science Foundation of China,China(81873154)President Foundation of Integrated Hospital of Traditional Chinese Medicine,Southern Medical University,China(1202103010)。
文摘Lycii Radicis Cortex(LRC)is a medicinal and food homologous plant with various pharmacological activities,including anti-tumor effects.This study explores the anti-tumor effect of LRC on non-small cell lung cancer(NSCLC)and its molecular mechanism using mice bearing Lewis lung carcinoma cells.LRC significantly suppressed the growth of NSCLC.Besides,RNA sequencing of mice tumors and hematoxylin&eosin and immunofluorescence staining revealed that LRC promoted the infiltration of T lymphocytes,specifically GZMB~+CD8~+T lymphocytes,in tumor tissues.The Gene Set Enrichment Analysis of spleen RNA indicated that LRC up-regulated PD-1-downstream pathways,suggesting that LRC exerted its effects through the PDL1/PD-1 pathway.Further experiments revealed that LRC interacted with PD-L1,blocking PD-L1/PD-1 binding and thus restoring the T cell killing activity on tumor cells.Together,these results support using LRC as healthy food to improve anti-tumor immunity in patients with NSCLC.
基金supported by the National Natural Science Foundation of China,Nos.82272171(to ZY),82271403(to XL),81941011(to XL),31971279(to ZY),31730030(to XL)the Natural Science Foundation of Beijing,No.7222004(to HD).
文摘The presence of endogenous neural stem/progenitor cells in the adult mammalian brain suggests that the central nervous system can be repaired and regenerated after injury.However,whether it is possible to stimulate neurogenesis and reconstruct cortical layers II to VI in non-neurogenic regions,such as the cortex,remains unknown.In this study,we implanted a hyaluronic acid collagen gel loaded with basic fibroblast growth factor into the motor cortex immediately following traumatic injury.Our findings reveal that this gel effectively stimulated the proliferation and migration of endogenous neural stem/progenitor cells,as well as their differentiation into mature and functionally integrated neurons.Importantly,these new neurons reconstructed the architecture of cortical layers II to VI,integrated into the existing neural circuitry,and ultimately led to improved brain function.These findings offer novel insight into potential clinical treatments for traumatic cerebral cortex injuries.
文摘Dear Editor,The importance of the medial entorhinal cortex(MEC)for memory and spatial navigation has been shown repeatedly in many species,including mice and humans[1,2].It is,therefore,not surprising that the connectivity of this structure has been studied extensively over the past century,mainly using a range of anterograde and retrograde anatomical tracers[3].
基金supported by the National Natural Science Foundation of China,Nos.82030071(to JH),82272495(to YC)Science and Technology Major Project of Changsha,No.kh2103008(to JH)Graduate Students’Independent Innovative Projects of Hunan Province,No.CX20230311(to YJ)。
文摘Spinal cord injury typically causes corticospinal tract disruption.Although the disrupted corticospinal tract can self-regenerate to a certain degree,the underlying mechanism of this process is still unclear.N6-methyladenosine(m^(6)A)modifications are the most common form of epigenetic regulation at the RNA level and play an essential role in biological processes.However,whether m^(6)A modifications participate in corticospinal tract regeneration after spinal cord injury remains unknown.We found that expression of methyltransferase 14 protein(METTL14)in the locomotor cortex was high after spinal cord injury and accompanied by elevated m^(6)A levels.Knockdown of Mettl14 in the locomotor cortex was not favorable for corticospinal tract regeneration and neurological recovery after spinal cord injury.Through bioinformatics analysis and methylated RNA immunoprecipitation-quantitative polymerase chain reaction,we found that METTL14 regulated Trib2 expression in an m^(6)A-regulated manner,thereby activating the mitogen-activated protein kinase pathway and promoting corticospinal tract regeneration.Finally,we administered syringin,a stabilizer of METTL14,using molecular docking.Results confirmed that syringin can promote corticospinal tract regeneration and facilitate neurological recovery by stabilizing METTL14.Findings from this study reveal that m^(6)A modification is involved in the regulation of corticospinal tract regeneration after spinal cord injury.
基金Supported by Hunan Provincial Postgraduate Scientific Research Innovation Project(CX20231270).
文摘[Objectives]This study was conducted to investigate the alleviating effect of Phellodendri Chinensis Cortex extract on the phytotoxicity of pretilachlor in rice.[Methods]In addition to CK,Phellodendri Chinensis Cortex extract and pretilachlor with different gradients were added to the culture medium,and rice seeds with the same bud length were evenly placed in the culture medium.After 10 and 15 d of culture,the plant height and fresh weight of rice seedlings were measured and the alleviation rate was calculated.[Results]Ten days after application,the plant height of treatment 8(pretilachlor:extract concentration ratio of 25:200)was alleviated with an alleviation rate of 21.72%,and the fresh weight of treatment 9(pretilachlor:extract concentration ratio of 25:400)was alleviated with an alleviation rate of 31.04%.Fifteen days after treatment,the plant height of treatment 6(pretilachlor:extract concentration ratio of 25:50)showed a better alleviating effect,and the fresh weight of treatment 8(pretilachlor:extract concentration ratio of 25:200)exhibited a better alleviating effect,with an alleviation rate of 22.39%.Meanwhile,it was found that the extract of Phellodendri Chinensis Cortex could alleviate the increase of POD activity in rice leaves caused by pretilachlor.Meanwhile,it was found that the extract of Phellodendri Chinensis Cortex promoted the expression of CAT in rice seedlings,thus significantly increasing its activity and alleviating the toxicity of pretilachlor to rice.[Conclusions]This study can provide technical support for the screening and field application of plant-derived safeners.
基金supported by grants from the National Natural Science Foundation of China(82271243 and 82101318)Shaanxi Province Key Research and Development Plan(2024SF-ZDCYL-01-13)+1 种基金the support funding from Fourth Military Medical University(2024JC005,2020AXJHHJ,and XJZT24JC27)Liaoning Provincial Joint Science and Technology Program(2023-MSLH-345).
文摘The anterior cingulate cortex(ACC)has recently been proposed as a key player in the representation of itch stimuli.However,to date,little is known about the contribution of specific ACC interneuron populations to itch processing.Using c-Fos immunolabeling and in vivo Ca2+imaging,we reported that both histamine and chloroquine stimuli-induced acute itch caused a marked enhancement of vasoactive intestinal peptide(VIP)-expressing interneuron activity in the ACC.Behavioral data indicated that optogenetic and chemogenetic activation of these neurons reduced scratching responses related to histaminergic and non-histaminergic acute itch.Similar neural activity and modulatory role of these neurons were seen in mice with chronic itch induced by contact dermatitis.Together,this study highlights the importance of ACC VIP+neurons in modulating itch-related affect and behavior,which may help us to develop novel mechanism-based strategies to treat refractory chronic itch in the clinic.
基金supported by the Anhui Provincial Department of Education Outstanding Young Teachers Cultivation Key Project(No.YQZD2023046)the Anhui University of Traditional Chinese Medicine School Talent Support Program Project(Nos.DT2400000222 and DT2100000545)。
文摘Objective:To elucidate the specific mechanisms by which electroacupuncture(EA)alleviates anxiety and fear behaviors associated with posttraumatic stress disorder(PTSD),focusing on the role of lipocalin-2(Lcn2).Methods:The PTSD mouse model was subjected to single prolonged stress and shock(SPS&S),and the animals received 15 min sessions of EA at Shenmen acupoint(HT7).Behavioral tests were used to investigate the effects of EA at HT7 on anxiety and fear.Western blotting and enzyme-linked immunosorbent assay were used to quantify Lcn2 and inflammatory cytokine levels in the prefrontal cortex(PFC).Additionally,the activity of PFC neurons was evaluated by immunofluorescence and in vivo electrophysiology.Results:Mice subjected to SPS&S presented increased anxiety-and fear-like behaviors.Lcn2 expression in the PFC was significantly upregulated following SPS&S,leading to increased expression of the proinflammatory cytokines tumor necrosis factor-a and interleukin-6 and suppression of PFC neuronal activity.However,EA at HT7 inhibited Lcn2 release,reducing neuroinflammation and hypoexcitability in the PFC.Lcn2 overexpression mitigated the effects of EA at HT7,resulting in anxiety-and fear-like behaviors.Conclusion:EA at HT7 can ameliorate PTSD-associated anxiety and fear,and its mechanism of action appears to involve the inhibition of Lcn2-mediated neural activity and inflammation in the PFC.
基金Supported by the Suzhou Science and Technology Bureau(No.SKY2023175)the Project of State Key Laboratory of Radiation Medicine and Protection+6 种基金Soochow University(No.GZK1202309)the Advantage Subject Lifting Project(No.XKTJ-XK202412)the Suzhou Science and Education for Strengthening Healthcare(No.MSXM2024010)the Suzhou Medical Key Supported Disciplines(No.SZFCXK202118)the Youth Scientific Research Fund Project of Kunshan Hospital of Traditional Chinese Medicine(No.2024QNJJ06)the Postgraduate Research&Practice Innovation Program of Jiangsu Province(No.SJCX23_1673)the Undergraduate Training Program for Innovation and Entrepreneurship,Soochow University(No.202310285162Y).
文摘AIM:To investigate the postnatal development of parvalbumin(PV)-positive gamma-aminobutyric acid(GABA)interneurons and the co-expression of perineuronal nets(PNNs)and PV in the visual cortex of rats,as well as the regulatory effects of fluoxetine(FLX)treatment and binocular form deprivation(BFD)on these indices.METHODS:Wistar rats were assigned to three experimental cohorts:1)Age-related groups:postnatal week(PW)1,PW3,PW5,PW7,and PW9;2)FLX treatment duration groups:FLX 0W,FLX 2W,FLX 4W,FLX 6W,and FLX 8W;3)Intervention groups:control(Cont),FLX,BFD,and BFD+FLX.The levels of PNNs,PV,and PNNs/PV coexpression in the visual cortex were detected and analyzed.RESULTS:The density of PV-positive cells and the coexpression of PNNs and PV increased gradually with the maturation of the visual cortex(b=0.960,P<0.01).The ratio of PV-positive cells surrounded by PNNs to total PV-positive cells(PNNs+/PV+/total PV+)was significantly decreased in the FLX 4W group(χ^(2)=9.03,P=0.003).There was no significant difference in the PNNs+/PV+/total PV+ratio between the FLX and BFD groups(χ^(2)=1.08,P=0.161),but a significant difference was observed between the BFD+FLX group and the BFD group(χ^(2)=5.82,P<0.01).CONCLUSION:The number of PV-positive neurons and PNNs-surrounded PV neurons in the rat visual cortex increases postnatally and reaches adult levels by postnatal week 7.Chronic FLX treatment downregulates these expressions.Combined 4-week FLX treatment and BFD exerts a more significant inhibitory effect on the PNNs+/PV+/total PV+ratio than either intervention alone.
文摘To determine the addition amount of Phellodendri Chinensis Cortex residue for composting,this study designed four Phellodendri Chinensis Cortex residue treatments of 100(A1),150(A2),200(A3),and 250(A4).Then,mushroom substrate residue,rice husks,and pig manure were added,and the cellulose-degrading strain ZG2-3 was inoculated at 5%for composting.The inoculation of a commercially available microbial agent was taken as the positive control(PC),and no inoculation of microbial agent as the blank control(CK).The effect of different treatments on the heavy metal content,nutrients,physicochemical properties,and microbial counts of compost and the seed germination index(GI)were studied and compared.The results showed that except that in CK,the content of heavy metals in other treatments did not exceed the standard limits.With the increase in the addition amount of Phellodendri Chinensis Cortex residue,the content of available nitrogen,available phosphorus,available potassium,and total nutrients in the compost also increased.Adding microbial agent significantly increased the content of total nutrients,available nitrogen,available phosphorus,available potassium,total nitrogen,total phosphorus,and total potassium in the compost,while reducing the content of organic matter.The GI was the highest in A4 treatment,reaching 85.33%,and it followed a trend of A3>PC>CK.This indicated that the inoculation of microbial agent accelerated the maturation of compost,and ZG2-3 outperformed the commercially available Bacillus subtilis.Overall,the A4 treatment(250 g Phellodendri Chinensis Cortex residue+125 g mushroom substrate residue+125 g rice husks+1000 g pig manure+inoculation of 5%ZG2-3)performed well in terms of nutrients content,physicochemical properties,and GI and had good safety,being the optimal formula for composting.
基金supported by grants from the National Natural Science Foundation of China(31970902,U22A20306,and 3192010300)the Municipal Administration of Hospitals Incubating Program(PZ2023009)+1 种基金the Key-Area R&D Program of Guangdong Province(2019B030335001)the Autism Research Special Fund of Zhejiang Foundation for Disabled Persons(2022003).
文摘Anxiety disorder is a major symptom of autism spectrum disorder(ASD)with a comorbidity rate of~40%.However,the neural mechanisms of the emergence of anxiety in ASD remain unclear.In our study,we found that hyperactivity of basolateral amygdala(BLA)pyramidal neurons(PNs)in Shank3 InsG3680 knock-in(InsG3680+/+)mice is involved in the development of anxiety.Electrophysiological results also showed increased excitatory input and decreased inhibitory input in BLA PNs.Chemogenetic inhibition of the excitability of PNs in the BLA rescued the anxiety phenotype of InsG3680+/+mice.Further study found that the diminished control of the BLA by medial prefrontal cortex(mPFC)and optogenetic activation of the mPFC-BLA pathway also had a rescue effect,which increased the feedforward inhibition of the BLA.Taken together,our results suggest that hyperactivity of the BLA and alteration of the mPFC-BLA circuitry are involved in anxiety in InsG3680+/+mice.
文摘Schizophrenia is a multifaceted neurodevelopmental disorder characterized by hallucinations,delusions,cognitive deficits,and emotional dysregulation.The prefrontal cortex(PFC),essential for executive functions,working memory,and emotional regulation,is notably impaired in this condition.This review consolidates current insights into the role of PFC dysfunction in schizophrenia,with a focus on its implications for therapeutic strategies.The neuroanatomical and neurobiological foundations of PFC dysfunction are explored,emphasizing structural abnormalities,functional dysconnectivity,and microcircuit disruptions that contribute to cognitive deficits and impaired decision-making.Clinical implications are discussed,particularly the correlation between PFC dysfunction and the severity and progression of schizophrenia symptoms.Additionally,pharmacological and non-pharmacological approaches aimed at modulating PFC activity are reviewed as potential therapeutic options.In conclusion,a deeper understanding of PFC dysfunction is pivotal for developing targeted treatments,and ongoing research offers promising avenues for enhancing outcomes for individuals affected by this debilitating disorder.
