apoptosis

摘要： Previous studies have shown that berberine has neuroprotective effects against Alzheimer’s disease,including antagonizing tau phosphorylation,and inhibiting acetylcholinesterase activity and neural cell apoptosis.However,its low bioavailability and adverse reactions with conventional administration limit its clinical application.In this study,we prepared berberine nanoliposomes using liposomes characterized by low toxicity,high entrapment efficiency,and biodegradability,and modified them with lactoferrin.Lactoferrin-modified berberine nanoliposomes had uniform particle size and high entrapment efficiency.We used the lactoferrin-modified berberine nanoliposomes to treat a mouse model of Alzheimer’s disease established by injection of amyloid-beta 1-42 into the lateral ventricle.Lactoferrin-modified berberine nanoliposomes inhibited acetylcholinesterase activity and apoptosis in the hippocampus,reduced tau over-phosphorylation in the cerebral cortex,and improved mouse behavior.These findings suggest that modification with lactoferrin can enhance the neuroprotective effects of berberine nanoliposomes in Alzheimer’s disease.

摘要： Regulated cell death predominantly involves apoptosis,autophagy,and regulated necrosis.It is vital that we understand how key regulatory signals can control the process of cell death.Pin1 is a cis-trans isomerase that catalyzes the isomerization of phosphorylated serine or threonine-proline motifs of a protein,thereby acting as a crucial molecular switch and regulating the protein functionality and the signaling pathways involved.However,we know very little about how Pin1-associated pathways might play a role in regulated cell death.In this paper,we review the role of Pin1 in regulated cell death and related research progress and summarize Pin1-related pathways in regulated cell death.Aside from the involvement of Pin1 in the apoptosis that accompanies neurodegenerative diseases,accumulating evidence suggests that Pin1 also plays a role in regulated necrosis and autophagy,thereby exhibiting distinct effects,including both neurotoxic and neuroprotective effects.Gaining an enhanced understanding of Pin1 in neuronal death may provide us with new options for the development of therapeutic target for neurodegenerative disorders.

摘要： Chronic spinal cord compression(CSCC)is induced by disc herniation and other reasons,leading to movement and sensation dysfunction,with a serious impact on quality of life.Spontaneous disc herniation rarely occurs in rodents,and therefore establishing a chronic spinal cord compression(CSCC)animal model is of crucial importance to explore the pathogenesis and treatment of CSCC.The absence of secreted protein,acidic,and rich in cysteine(SPARC)leads to spontaneous intervertebral disc degeneration in mice,which resembles human disc degeneration.In this study,we evaluated whether SPARC-null mice may serve as an animal model for CSCC.We performed rod rotation test,pain threshold test,gait analysis,and Basso Mouse Scale score.Our results showed that the motor function of SPARC-null mice was weakened,and magnetic resonance images revealed compression at different spinal cord levels,particularly in the lumbar segments.Immunofluorescence staining and western blot assay showed that the absence of SPARC induced apoptosis of neurons and oligodendrocytes,activation of microglia/macrophages with M1/M2 phenotype and astrocytes with A1/A2 phenotype;it also activated the expression of the NOD-like receptor protein 3 inflammasome and inhibited brain-derived neurotrophic factor/tyrosine kinase B signaling pathway.Notably,these findings are characteristics of CSCC.Therefore,we propose that SPARC-null mice may be an animal model for studying CSCC caused by disc herniation.

摘要： Spinal cord injury is one of the leading causes of morbidity and mortality among young adults in many countries including the United States.Difficulty in the regeneration of neurons is one of the main obstacles that leave spinal cord injury patients with permanent paralysis in most instances.Recent research has found that preventing acute and subacute secondary cellular damages to the neurons and supporting glial cells can help slow the progression of spinal cord injury pathogenesis,in part by reactivating endogenous regenerative proteins including Noggin that are normally present during spinal cord development.Noggin is a complex protein and natural inhibitor of the multifunctional bone morphogenetic proteins,and its expression is high during spinal cord development and after induction of spinal cord injury.In this review article,we first discuss the change in expression of Noggin during pathogenesis in spinal cord injury.Second,we discuss the current research knowledge about the neuroprotective role of Noggin in preclinical models of spinal cord injury.Lastly,we explain the gap in the knowledge for the use of Noggin in the treatment of spinal cord injury.The results from extensive in vitro and in vivo research have revealed that the therapeutic efficacy of Noggin treatment remains debatable due to its neuroprotective effects observed only in early phases of spinal cord injury but little to no effect on altering pathogenesis and functional recovery observed in the chronic phase of spinal cord injury.Furthermore,clinical information regarding the role of Noggin in the alleviation of progression of pathogenesis,its therapeutic efficacy,bioavailability,and safety in human spinal cord injury is still lacking and therefore needs further investigation.

摘要： PANoptosis is a newly identified type of regulated cell death that consists of pyroptosis,apoptosis,and nec roptosis,which simultaneously occur during the pathophysiological process of infectious and inflammatory diseases.Although our previous lite rature mining study suggested that PANoptosis might occur in neuronal ischemia/repe rfusion injury,little experimental research has been reported on the existence of PANoptosis.In this study,we used in vivo and in vitro retinal neuronal models of ischemia/repe rfusion injury to investigate whether PAN optosis-like cell death(simultaneous occurrence of pyroptosis,apo ptosis,and necroptosis)exists in retinal neuronal ischemia/repe rfusion injury.Our results showed that ischemia/repe rfusion injury induced changes in morphological features and protein levels that indicate PANoptosis-like cell death in retinal neurons both in vitro and in vivo.Ischemia/repe rfusion inju ry also significantly upregulated caspase-1,caspase-8,and NLRP3 expression,which are important components of the PANoptosome.These results indicate the existence of PANoptosis-like cell death in ischemia/reperfusion injury of retinal neurons and provide preliminary experimental evidence for future study of this new type of regulated cell death.

摘要： Heat stress is an important influence on the male reproductive organs.Therefore,the effects of heat stress on genes or pathways related to the reproductive system of male mice were experimentally explored in this paper to further determine the effects of heat stimulation on mammals.Herein,models of heat-exposed mouse testicular tissue and heatexcited cells were successfully established.Many scorched vesicles were found after heat excitation of testis supporting cells,testicular mesenchymal(TM4)cells.Western blot,in situ terminal deoxynucleotide transferase dUTP Nick end labeling(TUNEL)and transmission electron microscopy showed that membrane rupture,mitochondrial damage and autophagic vesicles occurred in TM4 cells after thermal excitation.The N-segment fragment of the associated protein shear was increased,and the TUNEL result was positive.In conclusion,thermal excitation induced apoptosis and scorch death in TM4 cells.Thus,the Hippo pathway and apoptosis-related pathway were significantly enriched after heat stimulation in mouse testis,and the scorch death effect in TM4 cells was induced by heat excitation.

摘要： Schisandrin B(Sch B)is a monomer with anti-cancer and anti-inflammatory effects,which are isolated from the plant Schisandra chinensis(Turcz)Baillon.We investigated the anti-gastric cancer(GC)effects of Sch B and its underlying molecular mechanisms.The Cell Counting Kit-8 assay was used to determine the effects of Sch B on the viability of GC and normal cell lines.Hoechst/propidium iodide staining and flow cytometry were used to assess the apoptosis induction of Sch B.Western blotting was used to evaluate the effects of Sch B on downstream apoptotic proteins.The DCFH-DA fluorescent probe was used to assess the regulatory effects of Sch B on reactive oxygen species(ROS)levels and related signaling pathways in GC cells.The results showed that Sch B could regulate the phosphorylation level of mitogen-activated protein kinase(MAPK)by upregulating ROS accumulation in gastric cancer cells,and then reduce the expression of nuclear factor kappa B(NF-κB)and phosphorylated transcription 3(p-STAT3).In addition,Sch B downregulated the cell cycle proteins cyclin-dependent kinase 2/4/6 and cyclin D1/E,and arrested cells in the G0/G1 phase.Moreover,it also inhibited cell migration,which was reversed with Nacetylcysteine pretreatment.In summary,Sch B has killing effects on GC cells by upregulating the production of intracellular ROS and regulating the MAPK/STAT3/NF-κB signaling pathway,leading to the migration arrest and apoptosis of GC cells.

摘要： Liver cancer is the seventh most common malignant tumor in the world and is the second highest cause of death due to cancer.Quercetin,a flavonoid with low toxicity,widely exists in various fruits and vegetables.It has the potential to be a therapeutic agent against various cancers.This study aimed to demonstrate the anti-tumor effect of quercetin on HepG2 cells.Quercetin suppressed the HepG2 cell proliferation in a dose-dependent manner in cell viability assay.Induction of cell apoptosis was confirmed by apoptotic cells population(sub-G1 peak)detected by flow cytometer.A decrease in mitochondrial membrane potential and caspase-3 activation were also demonstrated in this study.Furthermore,quercetin induced HepG2 cell apoptosis through ROS-mediated phosphorylated ataxia-telangiectasia mutated,c-Jun Nterminal kinases,signal transducer,and activator of transcription 3(STAT-3),and Bax signaling pathways.These results suggest that quercetin has the potential to become an effective drug against the tumor.

摘要： Treadmill exercise and mesenchymal stem cell transplantation are both practical and effective methods for the treatment of cerebral ischemia.However,whether there is a synergistic effect between the two remains unclear.In this study,we established rat models of ischemia/reperfusion injury by occlusion of the middle cerebral artery for 2 hours and reperfusion for 24 hours.Rat models were perfused with bone marrow mesenchymal stem cell-derived exosomes(MSC-exos)via the tail vein and underwent 14 successive days of treadmill exercise.Neurological assessment,histopathology,and immunohistochemistry results revealed decreased neuronal apoptosis and cerebral infarct volume,evident synaptic formation and axonal regeneration,and remarkably recovered neurological function in rats subjected to treadmill exercise and MSC-exos treatment.These effects were superior to those in rats subjected to treadmill exercise or MSC-exos treatment alone.Mechanistically,further investigation revealed that the activation of JNK1/c-Jun signaling pathways regulated neuronal apoptosis and synaptic-axonal remodeling.These findings suggest that treadmill exercise may exhibit a synergistic effect with MSC-exos treatment,which may be related to activation of the JNK1/c-Jun signaling pathway.This study provides novel theoretical evidence for the clinical application of treadmill exercise combined with MSC-exos treatment for ischemic cerebrovascular disease.

摘要： Previous studies have shown that fibroblast growth factor 13 is downregulated in the brain of both Alzheimer’s disease mouse models and patients,and that it plays a vital role in the learning and memory.However,the underlying mechanisms of fibroblast growth factor 13 in Alzheimer’s disease remain unclear.In this study,we established rat models of Alzheimer’s disease by stereotaxic injection of amyloid-β(Aβ1-42)-induced into bilateral hippocampus.We also injected lentivirus containing fibroblast growth factor 13 into bilateral hippocampus to overexpress fibroblast growth factor 13.The expression of fibroblast growth factor 13 was downregulated in the brain of the Alzheimer’s disease model rats.After overexpression of fibroblast growth factor 13,learning and memory abilities of the Alzheimer’s disease model rats were remarkably improved.Fibroblast growth factor 13 overexpression increased brain expression levels of oxidative stress-related markers glutathione,superoxide dismutase,phosphatidylinositol-3-kinase,AKT and glycogen synthase kinase 3β,and anti-apoptotic factor BCL.Furthermore,fibroblast growth factor 13 overexpression decreased the number of apoptotic cells,expression of pro-apoptotic factor BAX,cleaved-caspase 3 and amyloid-βexpression,and levels of tau phosphorylation,malondialdehyde,reactive oxygen species and acetylcholinesterase in the brain of Alzheimer’s disease model rats.The changes were reversed by the phosphatidylinositol-3-kinase inhibitor LY294002.These findings suggest that overexpression of fibroblast growth factor 13 improved neuronal damage in a rat model of Alzheimer’s disease through activation of the phosphatidylinositol-3-kinase/AKT/glycogen synthase kinase 3βsignaling pathway.

摘要： Millimeter wave (MW) is an electromagnetic wave with a wavelength between 1 and 10 mm and a frequency of 30～300 GHz that can evoke multiple biological effects, both locally and globally. MW has been broadly used in clinical medicine. Although our previous work demonstrated that MW can inhibit sodium nitroprussiate (SNP)-induced apoptosis in chondrocytes, the precise mechanism of the anti-apoptotic activity remains to be elucidated.In this report, we investigated the cellular effects of MW in 5NP-induced apoptotic chondrocytes. We found that MW treatment could inhibit an SNP-induced mitochondrion-dependent pathway of apoptosis. MW treatment inhibited the loss of plasma membrane asymmetry(externalization of phosphatidylserine)，collapse of mitochondria) membrane potential，and activation of caspase-9 and caspase-3.Taken together, these results suggest that MW inhibits the mitochondrion-dependent pathway of apoptosis in chondrocytes and this may, in part，explain its clinical effect in the treatment of osteoarthritis.

摘要： Objectives: To investigate whether overexpression of Nurr1 (nuclear receptor-related factor 1) enhances the vulnerability ofSK-N-SH cells to neurotoxin 6-OHDA. Nurr1 is a transcription factor of the steriod/thyroxin hormone nuclear receptor superfamily that is highly expressed in mesencephalic dopamine(DA) system. Nurr1 is specifically required for the induction of ventral midbrain Dargic neurons and important for development and survival of mature Dargic neurons，the cells primarily lost inhuman Parkinson's disease (PD). Methods: a human neuroblastoma-derived cell line SK-N-SH which do not express endogenous Nurrl were transfected with the pBK-RSV-Nurr1 plasmid by LipofectAMINE and selected by G418.

摘要： Objectives: To investigate whether overexpression of Nurr1 (nuclear receptor-related factor 1) enhances the vulnerability ofSK-N-SH cells to neurotoxin 6-OHDA. Nurr1 is a transcription factor of the steriod/thyroxin hormone nuclear receptor superfamily that is highly expressed in mesencephalic dopamine(DA) system. Nurr1 is specifically required for the induction of ventral midbrain Dargic neurons and important for development and survival of mature Dargic neurons，the cells primarily lost inhuman Parkinson's disease (PD). Methods: a human neuroblastoma-derived cell line SK-N-SH which do not express endogenous Nurrl were transfected with the pBK-RSV-Nurr1 plasmid by LipofectAMINE and selected by G418.

摘要： Objectives: To investigate whether overexpression of Nurr1 (nuclear receptor-related factor 1) enhances the vulnerability ofSK-N-SH cells to neurotoxin 6-OHDA. Nurr1 is a transcription factor of the steriod/thyroxin hormone nuclear receptor superfamily that is highly expressed in mesencephalic dopamine(DA) system. Nurr1 is specifically required for the induction of ventral midbrain Dargic neurons and important for development and survival of mature Dargic neurons，the cells primarily lost inhuman Parkinson's disease (PD). Methods: a human neuroblastoma-derived cell line SK-N-SH which do not express endogenous Nurrl were transfected with the pBK-RSV-Nurr1 plasmid by LipofectAMINE and selected by G418.

摘要： Objectives: To investigate whether overexpression of Nurr1 (nuclear receptor-related factor 1) enhances the vulnerability ofSK-N-SH cells to neurotoxin 6-OHDA. Nurr1 is a transcription factor of the steriod/thyroxin hormone nuclear receptor superfamily that is highly expressed in mesencephalic dopamine(DA) system. Nurr1 is specifically required for the induction of ventral midbrain Dargic neurons and important for development and survival of mature Dargic neurons，the cells primarily lost inhuman Parkinson's disease (PD). Methods: a human neuroblastoma-derived cell line SK-N-SH which do not express endogenous Nurrl were transfected with the pBK-RSV-Nurr1 plasmid by LipofectAMINE and selected by G418.

摘要： Objectives: To investigate whether overexpression of Nurr1 (nuclear receptor-related factor 1) enhances the vulnerability ofSK-N-SH cells to neurotoxin 6-OHDA. Nurr1 is a transcription factor of the steriod/thyroxin hormone nuclear receptor superfamily that is highly expressed in mesencephalic dopamine(DA) system. Nurr1 is specifically required for the induction of ventral midbrain Dargic neurons and important for development and survival of mature Dargic neurons，the cells primarily lost inhuman Parkinson's disease (PD). Methods: a human neuroblastoma-derived cell line SK-N-SH which do not express endogenous Nurrl were transfected with the pBK-RSV-Nurr1 plasmid by LipofectAMINE and selected by G418.