Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective: Neuronal apoptosis is considered to be a critical process in spinal cord injury (SCI). Despite growing evidence of the antiapoptotic, anti-inflammatory, and modulation of ischemic injury tolerance effects of extracellular ubiquitin (eUb), existing studies have paid less attention to the impact of eUb in neurological injury disorders, particularly in SCI. This study aimed to investigate whether eUb can play a protective role in neurons, both in vitro and in vivo, and explores the underlying mechanisms. Methods: By utilizing an oxygen glucose deprivation cellular model and a SCI rat model, we firstly investigated the therapeutic effects of eUb on SCI and further explored its effects on neuronal autophagy and mitochondria-dependent apoptosis-related indicators, as well as the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mechanical target of rapamycin (mTOR) signaling pathway. Results: In the SCI models both in vivo and in vitro, early intervention with eUb enhanced neuronal autophagy and inhibited mitochondrial apoptotic pathways, significantly mitigating SCI. Further studies had shown that this protective effect of eUb was mediated through its receptor, CXC chemokine receptor type 4 (CXCR4). Additionally, eUb-enhanced autophagy and antiapoptotic effects were possibly associated with inhibiting the PI3K/Akt/mTOR pathway. Conclusion In summary, the study demonstrates that early eUb intervention can enhance autophagy and inhibit mitochondrial apoptotic pathways via CXCR4, protecting neurons and promoting SCI repair.

Objective: To investigate the effects of β-caryophyllene(BCP) on the browning of white adipose tissue in obese mice and the related mechanisms. Methods: An obese mouse model was establishedviaintraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution [14.4 mg/(kg·d)] in male Kunming mice. Obesity model mice were randomly divided into a model group(Model group) and a BCP administration group(BCP-50 group); normal diet mice were set up as a control group(Control group), with 8 mice in each group. BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group, while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks. The oral glucose tolerance test was performed at the end of 4-week administration, and mice were executed after overnight fasting at the end of the experiment, and blood samples and adipose tissues were rapidly collected for subsequent experimental tests. The kit was used to detect serological-related indexes; hematoxylin-eosin staining was conducted to observe the morphology of adipose tissue; immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1) in adipose tissue; Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α), peroxisome proliferator-activated receptor γ(PPARγ), UCP1 and cannabinoid receptor 2(CNR2) proteins in epididymal white adipose(eWAT). Results: Compared with the model group, the body mass of obese mice in the BCP-50 group was significantly reduced(P<0.05), food intake was decreased(P<0.01), insulin resistance was improved(P<0.000 1), and the serum content of low-density lipoprotein cholesterol(LDL-C) and nonesterified fatty acid(NEFA) in the obese mice was significantly reduced(P<0.000 1 andP<0.01). Total cholesterol(TC), triglyceride(TG), and high-density lipoprotein cholesterol(HDL-C) contents did not change significantly. In addition, the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P<0.05); the adipocytes in eWAT and BAT were reduced; and the expression of the UCP1 protein was significantly elevated(P<0.01 andP<0.05). In addition to UCP1, the expression levels of PGC1α, PPARγ, and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P<0.01,P<0.05, andP<0.001). Conclusion β-caryophyllene promotes white adipose tissue browning through up-regulating PPARγ/PGC-1α/UCP1 pathway expression, thus improving obesity.

Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P＜0.05),food intake was decreased(P＜0.01),insulin resistance was improved(P＜0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P＜0.000 1 and P＜0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P＜0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P＜0.01 and P＜0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P＜0.01,P＜0.05,and P＜0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.

Objective To study the effect and mechanism of Anchusa italica Retz on cerebral ischemia-reperfusion inju-ry in rats based on the target network of active compounds in Anchusa italica Retz.Methods The rat model of cerebral ische-mia-reperfusion injury was established by the thread occlusion method.After performing ischemia for 1.5 h and then reperfusion for 24 h,the neurological function of rats was scored and the volume of cerebral infarction was measured by the 2,3,5-triphenyltet-razolium chloride staining method.The molecular network analysis technique of network pharmacology,protein-protein interaction network,gene ontology(GO)enrichment analysis,KEGG signal pathway analysis,and molecular docking was used to study the mechanism of Anchusa italica Retz in the treatment of cerebral ischemia-reperfusion injury.Results The administration of An-chusa italica Retz could significantly improve the neurobehavioral dysfunction caused by cerebral ischemia-reperfusion injury and reduce the pathological injury of brain tissue.Anchusa italica Retz could regulate inflammation,apoptosis,protein phosphorylation,and other biological processes through 143 ischemic stroke-related targets,and interfere with the TNF signal pathway,VEGF signal pathway,HIF-1 signal pathway,and other pathways.Conclusion Network pharmacology and experimental verification had shown that Anchusa italica Retz could effectively reduce brain injury and protect neurological function through multi-target,multi-mechanism,and holistic treatment of cerebral ischemia-reperfusion injury.

Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P＜0.05),food intake was decreased(P＜0.01),insulin resistance was improved(P＜0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P＜0.000 1 and P＜0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P＜0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P＜0.01 and P＜0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P＜0.01,P＜0.05,and P＜0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.

Objective To investigate the effects of β-caryophyllene(BCP)on the browning of white adipose tissue in obese mice and the related mechanisms.Methods An obese mouse model was established via intraperitoneal injection of a high-fat diet supplemented with propylthiouracil saline solution[14.4 mg/(kg·d)]in male Kun-ming mice.Obesity model mice were randomly divided into a model group(Model group)and a BCP administra-tion group(BCP-50 group);normal diet mice were set up as a control group(Control group),with 8 mice in each group.BCP administration was given by gavage at a dose of 50 mg/kg once in the morning and once in the evening in the BCP-administered group,while the rest of the group was administered by gavage with aqueous solution of Tween 80 for 4 weeks.The oral glucose tolerance test was performed at the end of 4-week administration,and mice were executed after overnight fasting at the end of the experiment,and blood samples and adipose tissues were rap-idly collected for subsequent experimental tests.The kit was used to detect serological-related indexes;hematoxy-lin-eosin staining was conducted to observe the morphology of adipose tissue;immunohistochemical staining was carried out to observe the expression of uncoupling protein 1(UCP1)in adipose tissue;Western blot was employed to detect expression of peroxisome proliferator-activated receptor γ coactivator1-α(PGC1α),peroxisome prolifera-tor-activated receptor γ(PPARγ),UCP1 and cannabinoid receptor 2(CNR2)proteins in epididymal white adi-pose(eWAT).Results Compared with the model group,the body mass of obese mice in the BCP-50 group was significantly reduced(P＜0.05),food intake was decreased(P＜0.01),insulin resistance was improved(P＜0.000 1),and the serum content of low-density lipoprotein cholesterol(LDL-C)and nonesterified fatty acid(NE-FA)in the obese mice was significantly reduced(P＜0.000 1 and P＜0.01).Total cholesterol(TC),triglycer-ide(TG),and high-density lipoprotein cholesterol(HDL-C)contents did not change significantly.In addition,the adiposity coefficient and eWAT specific gravity of obese mice in the BCP-50 group were significantly decreased(P＜0.05);the adipocytes in eWAT and BAT were reduced;and the expression of the UCP1 protein was signifi-cantly elevated(P＜0.01 and P＜0.05).In addition to UCP1,the expression levels of PGC1α,PPARγ,and CNR2 proteins in the eWAT of obese mice in the BCP-50 group were also significantly elevated(P＜0.01,P＜0.05,and P＜0.001).Conclusion β-caryophyllene promotes white adipose tissue browning through up-regula-ting PPARγ/PGC-1α/UCP1 pathway expression,thus improving obesity.