BACKGROUND:Parkinson's disease is a multifactorial neurological disorder characterized by progressive loss of dopaminergic neurons,and dimethyl fumarate(DMF)has potent neuroprotective and immunomodulatory effects in neurodegenerative diseases. OBJECTIVE:To explore the neuroprotective mechanism of DMF in a mouse model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease. METHODS:Twenty-four C57BL/6 mice were selected and randomly divided into control group,model group,low-dose DMF,and high-dose DMF groups.An animal model of Parkinson's disease was established in the latter three groups by intraperitoneal injection of 30 mg/kg MPTP,once a day for 5 consecutive days.Intragastric administration was given 30 minutes after each injection of MPTP.Mice in the low-dose DMF group(30 mg/kg)and high-dose DMF group(50 mg/kg)were intragastrically administered once a day for 7 consecutive days.The control and model groups were initially administered the same dose of normal saline.Behavioral testing,western blot,oxidative stress marker detection,and immunohistochemical staining were used to analyze the regulatory effects of DMF on oxidative stress and Keap1/Nrf2 signaling pathway in MPTP-induced Parkinson's disease mice,as well as the protective mechanism of DMF on degeneration of dopamine neurons. RESULTS AND CONCLUSION:Compared with the model group,mice in the low-dose DMF group exhibited significant improvements in motor retardation and postural imbalance(P<0.01),with even more remarkable improvements observed in the high-dose DMF group(P<0.01).Compared with the control group,the model group showed a significant increase in the oxidative stress marker malondialdehyde and a decrease in superoxide dismutase expression(P<0.01).Compared with the model group,the low-dose DMF group reduced malondialdehyde production and increased superoxide dismutase expression(P<0.01),and similar improvements were observed in the high-dose DMF group(P<0.01).Immunohistochemical and western blot assays demonstrated a significant decrease in the number of dopaminergic neurons and tyrosine hydroxylase protein expression in the substantia nigra of mice in the model group compared with the control group(P<0.01).However,in the low-dose DMF group,there was an increase in the number of dopaminergic neurons and tyrosine hydroxylase protein expression in the substantia nigra(P<0.01),with even more significant improvements in the high-dose DMF group(P<0.01).Western blot results revealed that the model group exhibited elevated Keap1 protein expression and decreased Nrf2 protein expression.In contrast,the DMF groups showed reduced Keap1 protein expression and increased Nrf2 protein expression compared to the model group(P<0.01).To conclude,DMF regulates the Keap1/Nrf2 pathway in the substantia nigra of mice with Parkinson's disease,and this regulatory effect is positively correlated with the dose of DMF(P<0.01).Therefore,we infer that DMF exerts neuroprotective effects through the Keap1/Nrf2 signaling pathway.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Background: Nasopharyngeal carcinoma (NPC) is characterized by high programmed death-ligand 1 (PD-L1) expression and abundant infiltration of non-malignant lymphocytes, which renders patients potentially suitable candidates for immune checkpoint blockade therapies. Palate, lung, and nasal epithelium clone (PLUNC) inhibit the growth of NPC cells and enhance cellular apoptosis and differentiation. Currently, the relationship between PLUNC (as a tumor-suppressor) and PD-L1 in NPC is unclear. Methods: We collected clinical samples of NPC to verify the relationship between PLUNC and PD-L1. PLUNC plasmid was transfected into NPC cells, and the variation of PD-L1 was verified by western blot and immunofluorescence. In NPC cells, we verified the relationship of PD-L1, activating transcription factor 3 (ATF3), and β-catenin by western blot and immunofluorescence. Later, we further verified that PLUNC regulates PD-L1 through β-catenin. Finally, the effect of PLUNC on β-catenin was verified by co-immunoprecipitation (Co-IP). Results: We found that PLUNC expression was lower in NPC tissues than in paracancer tissues. PD-L1 expression was opposite to that of PLUNC. Western blot and immunofluorescence showed that β-catenin could upregulate ATF3 and PD-L1, while PLUNC could downregulate ATF3/PD-L1 by inhibiting the expression of β-catenin. PLUNC inhibits the entry of β-catenin into the nucleus. Co-IP experiments demonstrated that PLUNC inhibited the interaction of DEAD-box helicase 17 (DDX17) and β-catenin. Conclusions PLUNC downregulates the expression of PD-L1 by inhibiting the interaction of DDX17/β-catenin in NPC.

Objective To investigate the mechanism of electroacupuncture to improve gastric motility in functional dyspep-sia(FD)model rats by regulating enteric nervous system through PI3K/Akt signaling pathway.Methods SPF grade SD rats were used and randomly divided into blank group,model group,and electroacupuncture group.The multifactorial stress inter-vention method was used in model group and electroacupuncture group to construct the FD rat model,and the modeling period was 14 days.After successful modeling,the electroacupuncture group was treated with electroacupuncture on the ST 36 and LR3 for 10 days.The body weight and food intake of the rats were measured three times at the beginning of the experiment(0 d),at the end of the modeling period(14 d),and at the end of the electroacupuncture intervention(24 d),respectively.At the end of the intervention,the intragastric residual rate,the morphological structure of gastric antrum,and the protein expression levels and locations of PI3K,Akt,and GFAP in the gastric antrum tissue were measured in each group of rats.Results ① Before modeling,the difference between the body weight of rats in each group was not statistically significant(all P＞0.05).After elec-troacupuncture intervention,the body weight ranking of rats in each group was blank group＞electroacupuncture group＞mod-el group,and the differences between groups were all statistically significant(all P＜0.01).② Before modeling,the difference between the body intake of rats in each group was not statistically significant(all P＞0.05).After electroacupuncture interven-tion,the ranking of food intake of rats in each group was blank group＞electroacupuncture group＞model group,and the differ-ences between groups were all statistically significant(all P＜0.01).③ The ranking of intragastric residual rate of rats in each group was blank group＜electroacupuncture group＜model group,and the differences between groups were all statistically sig-nificant(all P＜0.05).④ There was no organic lesions such as hemorrhage,edema,or ulcer in the gastric antrum tissue of rats in each group.⑤The ranking of protein expression levels of PI3K and Akt in gastric antrum tissue of rats in each group was blank group＞the electroacupuncture group＞the model group,and the differences between the groups were all statistically sig-nificant(all P＜0.05).PI3K and Akt proteins were all expressed in the muscular layer of gastric antrum tissue.⑥The ranking of enteric glial cell(EGC)counting in the gastric antrum tissue of rats in each group was blank group＞electroacupuncture group＞model group,and the differences between groups were all statistically significant(all P＜0.05).Conclusion The mech-anism that electroacupuncture can improve gastric motility in FD model rats may be related to activation of PI3K/Akt signaling pathway in the muscle layer of gastric antrum tissue,upregulation of EGC,and improvement of enteric nervous system function.

Objective:To explore the effect of different swallowing tasks on cortex activation and functional connectivity in stroke survivors with dysphagia using functional near-infrared spectroscopy (fNIRS).Methods:Thirty stroke survivors with dysphagia performed three different swallowing tasks: swallowing action observation (SO), swallowing action execution (SE), and swallowing action imagination (SI). During each task, fNIRS was used to document the brain concentrations of oxyhemoglobin and deoxyhemoglobin. Cortex activation (β value) and brain functional connectivity were assessed.Results:Compared with the resting state, the areas activated during the SO task included the left primary sensory cortex and the right prefrontal cortex. During the SE and SI tasks the left prefrontal cortex and the left motor cortex were activated as well. Compared with hemorrhagic stroke survivors, ischemic stroke survivors showed significantly greater activation of the right primary sensory cortex, the right motor cortex, and the left primary sensory cortex during the SE task. Functional connectivity during the SO, SE and SI tasks was significantly greater than in the resting state, with the average connectivity values during the SE task significantly higher than during the SI task.Conclusions:Stroke survivors with dysphagia exhibit increased activation in the prefrontal cortex and primary sensory cortex during different swallowing tasks. Such tasks can improve their brain functional connectivity.

Objective To investigate the mechanism of electroacupuncture to improve gastric motility in functional dyspep-sia(FD)model rats by regulating enteric nervous system through PI3K/Akt signaling pathway.Methods SPF grade SD rats were used and randomly divided into blank group,model group,and electroacupuncture group.The multifactorial stress inter-vention method was used in model group and electroacupuncture group to construct the FD rat model,and the modeling period was 14 days.After successful modeling,the electroacupuncture group was treated with electroacupuncture on the ST 36 and LR3 for 10 days.The body weight and food intake of the rats were measured three times at the beginning of the experiment(0 d),at the end of the modeling period(14 d),and at the end of the electroacupuncture intervention(24 d),respectively.At the end of the intervention,the intragastric residual rate,the morphological structure of gastric antrum,and the protein expression levels and locations of PI3K,Akt,and GFAP in the gastric antrum tissue were measured in each group of rats.Results ① Before modeling,the difference between the body weight of rats in each group was not statistically significant(all P＞0.05).After elec-troacupuncture intervention,the body weight ranking of rats in each group was blank group＞electroacupuncture group＞mod-el group,and the differences between groups were all statistically significant(all P＜0.01).② Before modeling,the difference between the body intake of rats in each group was not statistically significant(all P＞0.05).After electroacupuncture interven-tion,the ranking of food intake of rats in each group was blank group＞electroacupuncture group＞model group,and the differ-ences between groups were all statistically significant(all P＜0.01).③ The ranking of intragastric residual rate of rats in each group was blank group＜electroacupuncture group＜model group,and the differences between groups were all statistically sig-nificant(all P＜0.05).④ There was no organic lesions such as hemorrhage,edema,or ulcer in the gastric antrum tissue of rats in each group.⑤The ranking of protein expression levels of PI3K and Akt in gastric antrum tissue of rats in each group was blank group＞the electroacupuncture group＞the model group,and the differences between the groups were all statistically sig-nificant(all P＜0.05).PI3K and Akt proteins were all expressed in the muscular layer of gastric antrum tissue.⑥The ranking of enteric glial cell(EGC)counting in the gastric antrum tissue of rats in each group was blank group＞electroacupuncture group＞model group,and the differences between groups were all statistically significant(all P＜0.05).Conclusion The mech-anism that electroacupuncture can improve gastric motility in FD model rats may be related to activation of PI3K/Akt signaling pathway in the muscle layer of gastric antrum tissue,upregulation of EGC,and improvement of enteric nervous system function.

Objective To investigate the protective effect of epigallocatechin gallate(EGCG)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease model mice.Methods Twenty-eight male C57BL/6J mice aged 6～8 weeks were randomly divided into four groups:the control group,the model group,the low-dose EGCG group[25 mg/(kg·d)],and the high-dose EGCG group[50 mg/(kg·d)].A Parkin-son's disease(PD)mouse model was established by intraperitoneal injection of MPTP at a dose of 30 mg/(kg·d)for 7 consecutive days.The protective effect of EGCG on MPTP-induced Parkinson's model mice was analyzed through behavioral index detection and Western blot method.Results(1)In the behavioral tests,compared with the model group,the movement distance and speed of mice treated with low-and high-dose EGCG were significantly improved(both P values<0.001).The mice in the high-dose EGCG treatment group also showed a significant advantage in the percentage of the central path distance(P<0.001).(2)Compared with the control group,the deposition of α-synuclein in the model group increased significantly(P<0.001).Compared with the model group,both the low-and high-dose EGCG groups reduced the deposition of α-synuclein(both P<0.001).(3)Compared with the control group,the expression levels of Beclin 1 and LC3 proteins in the substantia nigra region of mice in the model group decreased significantly(both P<0.001),while the expression level of p62 protein increased significantly(P<0.001).After treatment with EGCG,compared with the model group,the expression levels of Beclin 1 and LC3 proteins in mice of the low-dose EGCG group increased to varying degrees(P<0.01;P<0.001),and the expression level of p62 protein decreased significantly(P<0.001).In the high-dose EGCG group,the expression levels of Beclin 1 and LC3 proteins increased significantly(both P<0.001),and the expression level of p62 protein decreased significantly(P<0.001).Conclusion EGCG reduces alpha-synuclein deposition via the autophagy-lysosomal pathway and protects against MPTP-induced Parkinson's disease model mice.

Objective To investigate the protective effect of epigallocatechin gallate(EGCG)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease model mice.Methods Twenty-eight male C57BL/6J mice aged 6～8 weeks were randomly divided into four groups:the control group,the model group,the low-dose EGCG group[25 mg/(kg·d)],and the high-dose EGCG group[50 mg/(kg·d)].A Parkin-son's disease(PD)mouse model was established by intraperitoneal injection of MPTP at a dose of 30 mg/(kg·d)for 7 consecutive days.The protective effect of EGCG on MPTP-induced Parkinson's model mice was analyzed through behavioral index detection and Western blot method.Results(1)In the behavioral tests,compared with the model group,the movement distance and speed of mice treated with low-and high-dose EGCG were significantly improved(both P values<0.001).The mice in the high-dose EGCG treatment group also showed a significant advantage in the percentage of the central path distance(P<0.001).(2)Compared with the control group,the deposition of α-synuclein in the model group increased significantly(P<0.001).Compared with the model group,both the low-and high-dose EGCG groups reduced the deposition of α-synuclein(both P<0.001).(3)Compared with the control group,the expression levels of Beclin 1 and LC3 proteins in the substantia nigra region of mice in the model group decreased significantly(both P<0.001),while the expression level of p62 protein increased significantly(P<0.001).After treatment with EGCG,compared with the model group,the expression levels of Beclin 1 and LC3 proteins in mice of the low-dose EGCG group increased to varying degrees(P<0.01;P<0.001),and the expression level of p62 protein decreased significantly(P<0.001).In the high-dose EGCG group,the expression levels of Beclin 1 and LC3 proteins increased significantly(both P<0.001),and the expression level of p62 protein decreased significantly(P<0.001).Conclusion EGCG reduces alpha-synuclein deposition via the autophagy-lysosomal pathway and protects against MPTP-induced Parkinson's disease model mice.

Objective:To explore the effect of different swallowing tasks on cortex activation and functional connectivity in stroke survivors with dysphagia using functional near-infrared spectroscopy (fNIRS).Methods:Thirty stroke survivors with dysphagia performed three different swallowing tasks: swallowing action observation (SO), swallowing action execution (SE), and swallowing action imagination (SI). During each task, fNIRS was used to document the brain concentrations of oxyhemoglobin and deoxyhemoglobin. Cortex activation (β value) and brain functional connectivity were assessed.Results:Compared with the resting state, the areas activated during the SO task included the left primary sensory cortex and the right prefrontal cortex. During the SE and SI tasks the left prefrontal cortex and the left motor cortex were activated as well. Compared with hemorrhagic stroke survivors, ischemic stroke survivors showed significantly greater activation of the right primary sensory cortex, the right motor cortex, and the left primary sensory cortex during the SE task. Functional connectivity during the SO, SE and SI tasks was significantly greater than in the resting state, with the average connectivity values during the SE task significantly higher than during the SI task.Conclusions:Stroke survivors with dysphagia exhibit increased activation in the prefrontal cortex and primary sensory cortex during different swallowing tasks. Such tasks can improve their brain functional connectivity.