Mitochondrial autophagy is a unique mechanism that selectively clears dysfunctional or excess mitochondria,closely related to Alzheimer's disease(AD),which is characterized by aggregated neurotoxic proteins and dysfunctional mitochondria.Numerous recent studies have confirmed that traditional Chinese medicine can have significant therapeutic effects against AD,and its advantages including multi-target,multi-pathway,and multi-action mechanisms have become an important component of AD research.Chinese medicine formulas and monomeric active ingredients,such as Jiannaoyizhi Fang,Danggui Shaoyao Tang,alkaloids,and flavonoids,can regulate mitochondrial autophagy-related signaling pathways and targets,inhibit neuronal mitochondrial autophagy defects,and play a neuroprotective role.This review elaborates on the basic process of mitochondrial autophagy and its related signaling pathways and molecular mechanisms in the pathogenesis of AD,and considers the latest research progress on the use of traditional Chinese medicine to improve AD by regulating mitochondrial autophagy,to provide ideas and references for future basic research and clinical treatment.

Mitochondrial autophagy is a unique mechanism that selectively clears dysfunctional or excess mitochondria,closely related to Alzheimer's disease(AD),which is characterized by aggregated neurotoxic proteins and dysfunctional mitochondria.Numerous recent studies have confirmed that traditional Chinese medicine can have significant therapeutic effects against AD,and its advantages including multi-target,multi-pathway,and multi-action mechanisms have become an important component of AD research.Chinese medicine formulas and monomeric active ingredients,such as Jiannaoyizhi Fang,Danggui Shaoyao Tang,alkaloids,and flavonoids,can regulate mitochondrial autophagy-related signaling pathways and targets,inhibit neuronal mitochondrial autophagy defects,and play a neuroprotective role.This review elaborates on the basic process of mitochondrial autophagy and its related signaling pathways and molecular mechanisms in the pathogenesis of AD,and considers the latest research progress on the use of traditional Chinese medicine to improve AD by regulating mitochondrial autophagy,to provide ideas and references for future basic research and clinical treatment.

AIM:This study aims to investigate the therapeutic impact of bone marrow mesenchymal stem cell(MSC)-derived exosomes(MSC-Exos)on septic lung injury by targeting Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signaling pathway.METHODS:MSC-Exos were isolated from bone marrow MSCs using ultracentrifugation.The exosomes were characterized by transmission electron microscopy(TEM),nanoparticle tracking analysis(NTA),and Western blot.A septic lung injury model was established via cecal ligation and puncture(CLP).MSC-Exos were adminis-tered intraperitoneally 3 h after CLP.Blood and lung tissue samples were collected at 6,12,24,and 72 h after CLP.Con-centrations of interleukin-10(IL-10),IL-6,IL-1β,and tumor necrosis factor-α(TNF-α)were measured by ELISA.The lung tissue damage in mice was assessed by HE staining.Expression levels of TLR4 and NF-κB were detected by RT-qP-CR and Western blot.RESULTS:The results of TEM revealed typical round and oval exosome-like structures of MSC-Exos.Western blot showed positive expression of CD63,TSG101 and HSP-70.The results of NTA indicated that the parti-cle size of MSC-Exos was(107.5±16.6)nm.Septic lung injury began to manifest 12 h after CLP and progressively worsened,peaking at 72 h after CLP.At 6 h after CLP,the level of TNF-α was markedly elevated compared to the control group,reaching its peak at 72 h after CLP.At 12 h after CLP,the levels of IL-1β,IL-10,and IL-6 were elevated com-pared to the control group,and they reached their maximum point 72 h post-CLP.The MSC-Exos intervention group ex-hibited significantly reduced lung injury compared to the CLP group,as indicated by the lung pathology scoring.In the MSC-Exos intervention group,concentrations of IL-10,IL-1β,IL-6,and TNF-α peaked at 12 h after CLP,gradually de-clined,and returned to baseline levels by 72 h.TLR4 and NF-κB expression levels were significantly increased at 6 h af-ter CLP in the CLP group,peaking at 72 h.In contrast,MSC-Exos treatment normalized TLR4 and NF-κB expression levels at 72 h after CLP.CONCLUSION:Early intervention with bone marrow MSC-Exos significantly alleviated septic lung injury by reducing the inflammatory cytokine storm,likely through downregulation of the TLR4/NF-κB signaling path-way.

AIM:This study aims to investigate the therapeutic impact of bone marrow mesenchymal stem cell(MSC)-derived exosomes(MSC-Exos)on septic lung injury by targeting Toll-like receptor 4(TLR4)/nuclear factor-κB(NF-κB)signaling pathway.METHODS:MSC-Exos were isolated from bone marrow MSCs using ultracentrifugation.The exosomes were characterized by transmission electron microscopy(TEM),nanoparticle tracking analysis(NTA),and Western blot.A septic lung injury model was established via cecal ligation and puncture(CLP).MSC-Exos were adminis-tered intraperitoneally 3 h after CLP.Blood and lung tissue samples were collected at 6,12,24,and 72 h after CLP.Con-centrations of interleukin-10(IL-10),IL-6,IL-1β,and tumor necrosis factor-α(TNF-α)were measured by ELISA.The lung tissue damage in mice was assessed by HE staining.Expression levels of TLR4 and NF-κB were detected by RT-qP-CR and Western blot.RESULTS:The results of TEM revealed typical round and oval exosome-like structures of MSC-Exos.Western blot showed positive expression of CD63,TSG101 and HSP-70.The results of NTA indicated that the parti-cle size of MSC-Exos was(107.5±16.6)nm.Septic lung injury began to manifest 12 h after CLP and progressively worsened,peaking at 72 h after CLP.At 6 h after CLP,the level of TNF-α was markedly elevated compared to the control group,reaching its peak at 72 h after CLP.At 12 h after CLP,the levels of IL-1β,IL-10,and IL-6 were elevated com-pared to the control group,and they reached their maximum point 72 h post-CLP.The MSC-Exos intervention group ex-hibited significantly reduced lung injury compared to the CLP group,as indicated by the lung pathology scoring.In the MSC-Exos intervention group,concentrations of IL-10,IL-1β,IL-6,and TNF-α peaked at 12 h after CLP,gradually de-clined,and returned to baseline levels by 72 h.TLR4 and NF-κB expression levels were significantly increased at 6 h af-ter CLP in the CLP group,peaking at 72 h.In contrast,MSC-Exos treatment normalized TLR4 and NF-κB expression levels at 72 h after CLP.CONCLUSION:Early intervention with bone marrow MSC-Exos significantly alleviated septic lung injury by reducing the inflammatory cytokine storm,likely through downregulation of the TLR4/NF-κB signaling path-way.

Since the establishment of the Chinese Society of Therapeutic Radiation Oncology 33 years ago, radiation oncology has developed rapidly in China. Based on previous survey data, this paper summarizes and reviews the development of radiation oncology in China (excluding Hong Kong, Macao and Taiwan regions) from the perspectives of radiotherapy units, relevant professionals, equipment, technologies and subject development, and looks forward to the future direction, and proposes a new concept—" precision radiotherapy" .

OBJECTIVE: To detect pathogenic variant in a neonate suspected for Cornelia de Lange syndrome (CdLS). METHODS: Potential mutations of CdLS-related genes (NIPBL, SMC1A, SMC3, RAD21 and HDAC8) were detected by high-throughput target region capture and next-generation sequencing. Suspected variants was verified by Sanger sequencing. RESULTS: The child was found to harbor a heterozygous splice site variant, c.6109-1G>A, of the NIPBL gene. Sanger sequencing suggested that neither parent has carried the same variant, suggesting that it was de novo. The variant was unreported by HGMD and ExAC database, and was predicted to alter an acceptor splicing site. No pathogenic variants of SMC1A, SMC3, RAD21 and HDAC8 genes were detected. CONCLUSION The heterozygous c.6109-1G>A splicing variant of the NIPBL gene may underlie the disease in this child. Above finding has expanded the variant spectrum of the NIPBL gene.
Cell Cycle Proteins ; genetics ; De Lange Syndrome ; genetics ; Genetic Testing ; Genetic Variation ; High-Throughput Nucleotide Sequencing ; Humans ; Infant, Newborn ; Mutation ; Phenotype

Objective To investigate the effect of hypothyroxinemia on emotion and hippocampus neurons in developing rats.Methods Sixty-nine healthy postnatal day (PD) 1 rats were randomly divided into control group (n =36) and experimental group (n =33).On PD1,experimental group was bilaterally thyroidectomized to establish hypothyroxinemia model,the control group was only given thyroid exposure operation without thyroid resection.On PD10,21,40,serum triiodothyronine (T3),thyroxine (T4),thyrotropicstimulating hormone (TSH) were detected by radioimmunoassay.Tail suspension test,forced swimming test,the elevated-plus maze and open field were respectively employed to detect the anxiety/depression like behavior on PD30,31,32,33.Nisslg staining was used to determine the survival of neurons at PD10,21,40 in hippocampus CA1,CA3,DG regions.Results Serum T4 levels on PD10,21,40 in experimental group decreased significantly as compared with control group (P ＜0.01),while there was no significant difference in serum T3 or TSH level (P ＞ 0.05).In the tail suspension test,immobility time of experimental group [(197.00 ± 19.50) s] was longer than control group [(158.33 ± 32.90) s,P ＜0.05].In the forced swimming test,immobility time of experimental group[(92.11 ± 35.24) s] was longer than control group [(62.00 ± 23.73) s,P ＜ 0.05].In the elevated plus-maze test,total number of arm entries and closed arm entries in experimental group were increased as compared with control group(P ＜ 0.05),percentage of closed arm/total time of experimental group was decreased as compared with control group(P ＜ 0.05).In the open field,there was no obvious difference between the two groups(P ＞ 0.05).On PD10,21,40,the amount of neurons in DG region of experimental group were less than control group(P ＜0.05),while there was no significant difference in CA1 or CA3 on PD10,21,40(P ＞0.05).Contusions Hypothyroxinemia can cause depression,hyperactivity and hippocampus neuron damage of developing rats.