Objective To investigate the effect of dorsal repulsive axon guidance protein(Draxin)on the migration of trunk neural crest cells during the early development of embryonic mouse spinal cord.Methods Immunohistochemistry and in situ hybridization were used to detect the expression characteristics of Draxin in early embryonic spinal cord(8 mice each group);In situ hybridization was used to detect the change of migration characteristics of trunk neural crest cells in early embryonic spinal cord of different types of mouse(5 mice each group);in vitro culture method was used to check the effect of Draxin on the migration characteristics of embryonic mouse trunk neural crest cells(16 mice each group).Resultsβ-galactosidase gene Z(LacZ)gene was introduced when Draxin gene was knocked out to produce Draxin gene knockout mice.β-galactosidase staining was used to detect LacZ gene expression in Draxin knockout embryonic mice,and the result showed that Draxin expression was observed in the spinal cord of early embryonic mice since 9.5 days(E9.5).Draxin expression was obvious in the embryonic mice spinal cord in E10.5 period.In situ hybridization was used to detect the expression of Draxin gene in the spinal cord of wild type embryonic mice,and the result further verified the obvious expression of Draxin in the early embryonic mice spinal cord in El0.5 period.Sox10 in situ hybridization was used to detect neural crest cell migration in the spinal cord of embryonic mice in E10.5 period.The result showed that segmental migration of neural crest cells in the early embryonic spinal cord of some Draxin knockout mice was delayed compared with the wild type mice.The effect of Draxin on the migration of wild type early embryonic mice trunk neural crest cells in vitro was tested.The result showed that Draxin reduced the migration distance of neural crest cells in vitro.Conclusion In the early developmental stage of embryonic spinal cord(E9.5-E10.5),neural crest cells migrated exuberant.At the same time,Draxin plays an important inhibitory function in the formation of the specific migration pathways of trunk neural crest cells by promoting neural crest cells migrating away from Draxin expressing regions.

Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P＜0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P＜0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P＜0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P＜0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P＜0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.

This study aims to explore the mechanism of Jiaotai Pills in treating depression based on metabolomics and network pharmacology. The chemical constituents of Jiaotai Pills were identified by UHPLC-Orbitrap Exploris 480, and the targets of Jiaotai Pills and depression were retrieved from online databases. STRING and Cytoscape 3.7.2 were used to construct the protein-protein interaction network of core targets of Jiaotai Pills in treating depression and the "compound-target-pathway" network. DAVID was used for Gene Ontology(GO) function and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses of the core targets. The mouse model of depression was established with chronic unpredictable mild stress(CUMS) and treated with different doses of Jiaotai Pills. The behavioral changes and pathological changes in the hippocampus were observed. UHPLC-Orbitrap Exploris 120 was used for metabolic profiling of the serum, from which the differential metabolites and related metabolic pathways were screened. A "metabolite-reaction-enzyme-gene" network was constructed for the integrated analysis of metabolomics and network pharmacology. A total of 34 chemical components of Jiaotai Pills were identified, and 143 core targets of Jiaotai Pills in treating depression were predicted, which were mainly involved in the arginine and proline, sphingolipid, and neurotrophin metabolism signaling pathways. The results of animal experiments showed that Jiaotai Pills alleviated the depression behaviors and pathological changes in the hippocampus of the mouse model of CUMS-induced depression. In addition, Jiaotai Pills reversed the levels of 32 metabolites involved in various pathways such as arginine and proline metabolism, sphingolipid metabolism, and porphyrin metabolism in the serum of model mice. The integrated analysis showed that arginine and proline metabolism, cysteine and methionine metabolism, and porphyrin metabolism might be the key pathways in the treatment of depression with Jiaotai Pills. In conclusion, metabolomics combined with network pharmacology clarifies the antidepressant mechanism of Jiaotai Pills, which may provide a basis for the clinical application of Jiaotai Pills in treating depression.
Animals ; Drugs, Chinese Herbal/chemistry* ; Depression/genetics* ; Mice ; Network Pharmacology ; Metabolomics ; Male ; Disease Models, Animal ; Humans ; Protein Interaction Maps/drug effects* ; Antidepressive Agents

Diabetic nephropathy(DN)is a serious complication of diabetes mellitus and a leading cause of end-stage renal diseases.In DN patients,key pathological mechanisms include proteinuria,glomerulo-sclerosis,and fibrosis,largely driven by poor glycemic control and oxidative stress caused by prolonged hyperglycemia.This stress damages renal podocytes and triggers inflammatory mesenchymal infiltration of renal tubular cells,exacerbating the progression of proteinuria and fibrosis.Human umbilical cord-de-rived mesenchymal stem cells(hUC-MSCs)offer promising potential for treating DN due to their strong anti-oxidative properties.In this study,we developed a DN mouse model and treated the mouse via tail vein injections of hUC-MSCs(1×106 cells/mouse).The results indicated that hUC-MSCs significantly lowered fasting blood glucose levels(22.5±3.0 vs 14.7±1.1,P＜0.01)and improved glucose toler-ance,as shown by intraperitoneal glucose tolerance test(IPGTT)results(P＜0.05).Additionally,the renal function improved in hUC-MSCs-treated mice,with marked reductions in oxidative stress markers,including blood urea nitrogen(BUN),urinary creatinine(Ucr),urinary protein(PRO),superoxide dismutase(SOD),and malondialdehyde(MDA)(P＜0.05).Histological analyses through hematoxy-lin-eosin(H&E),Periodic Acid-Schiff(PAS),and Sirius red staining demonstrated alleviation of glo-merular mesangial hyperplasia,glomerular hypertrophy,and tubular inflammation.Furthermore,hUC-MSCs treatment downregulated the expression of oxidative stress-related proteins,such as NADPH oxi-dase 4(NOX4)and thioredoxin-interacting protein(TXNIP),and reduced reactive oxygen species(ROS)production(P＜0.05).Meanwhile,human renal cortical proximal tubule epithelial cells(HK-2 cells)were selected for validation in vitro experiments using high glucose treatment followed by super-natants of hUC-MSCs(MSC-CM),and Western blotting showed that the expression of both NOX4 and TXNIP was inhibited(P＜0.05)and ROS expression was reduced.In conclusion,hUC-MSC treatment effectively lowered blood glucose levels and improved renal function in DN mice,likely through the sup-pression of NOX4 expression and TXNIP-mediated oxidative stress.

Humans ; Osteoblastoma/surgery* ; Neck/surgery* ; Spinal Neoplasms ; Cervical Vertebrae

Objective To investigate the efficacy of the therapy of soothing liver and strengthening spleen(shortened as Shugan Jianpi therapy)in the treatment of active thyroid-associated ophthalmopathy(TAO)complicated with dry eye,and to provide a reference basis for clinical treatment.Methods A total of 108 patients with active TAO complicated with dry eye of liver depression and qi stagnation type were randomly divided into observation group and control group,54 patients in each group.Both groups were given conventional treatment for intervention of Graves'disease,and additionally the control group was given hormone shock therapy by intravenous injection of Methylprednisolone Sodium Succinate,and the observation group was treated with Chinese medicine prescription for soothing liver and strengthening spleen orally and intravenous injection of Methylprednisolone Sodium Succinate.The treatment period lasted for 12 weeks,and then the patients were followed up till to the 6th month.The changes of clinical activity score(CAS),proptosis,ocular surface disease index(OSDI),corneal fluorescein staining(FL),Schirmer I test(SIT)and tear film break-up time(BUT)in the two groups were observed before and after the treatment.After treatment,the clinical efficacy of the two groups was evaluated.Results(1)After 6 months of treatment,the total effective rate in the observation group was 94.44%(51/54)and that in the control group was 74.07%(40/54),and the intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P＜0.05).(2)After treatment,the CAS,OSDI score and proptosis of the patients in the two groups were all lower than those before treatment(P＜0.01),and the reduction in the observation group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the indicators of tear secretion function such as SIT,FL score and BUT of patients in the two groups were improved compared with those before treatment(P＜0.01),and the improvement in the observation group was significantly superior to that in the control group,the differences being all statistically significant(P＜0.01).Conclusion Shugan Jianpi therapy exerts certain clinical efficacy in treating patients with active TAO complicated with dry eye of liver depression and qi stagnation type,which can effectively relieve the proptosis,prolong the tear film break-up time,promote the secretion of tears and the repair of corneal epithelium,improve the visual function,and enhance the quality of life of the patients.

Objective To observe the effects of total saponins of Trillium tschonoskii Maxim(TST)on vascular cognitive impairment(VCI),neurovascular units(NVUs),and neural circuit integrity in rats.Methods Forty-eight male Sprague-Dawley(SD)rats were randomly divided into sham-operated group,model group,TST group(intragastric administration,100 mg/kg),and donepezil group(intragastric administration,0.45 mg/kg),and then subjected to ischemic stroke by 2-VO method(bilateral common carotid artery ligation)or sham surgery.After 28 days of intragastric administration,Mirros water maze test was performed to evaluate the spatial learning and memory abilities of rats in each group.HE and Nissl staining were used to observe the pathological changes of brain tissue in rats.The expression of synuclein(SYN)in rat hippocampus was observed by immunohistochemical staining.Changes in dendritic spines in rat's hippocampal neurons were observed by Golgi staining.Western blotting was used to detect the expression levels of IL-1β,IL-10,vascular endothelial growth factor A(VEGFA),postsynaptic density protein 95(PSD95),and growth associated protein 43(GAP43)in rat's hippocampus in each group.Results In Mirros water maze test,rats in model group showed significant prolonged escape latency(P＜0.05),and a significant reduction in the number of crossing platforms and the percentage of activity time in the target quadrant(P＜0.05)than those in sham-operated group;while rats in TST group and donepezil group showed significant shortened escape latency(P＜0.01),and significant increase of the number of times of crossing platforms and the percentage of activity time in the target quadrant(P＜0.05)than those in model group.Compared of sham-operated group,model group showed a decrease in the expression of SYN and the number of neurons,Nissl bodies,and dendritic spines in the CA1 region of the hippocampus(P＜0.05).Compared with model group,TST group and donepezil group showed an increase in the expression of SYN and the number of neurons,Nissl bodies,and dendritic spines in the CA1 region of the hippocampus(P＜0.05).Western blotting showed a significant increase in the expression of IL-1β and VEGF(P＜0.05),and a decrease in the expression of IL-10,PSD95,and GAP43(P＜0.01)in rat's hippocampus of model group than those in sham-operated group.Compared with model group,TST group and donepezil group showed a significant decrease in the expression of IL-1β(P＜0.05),and an increase in the expression of VEGFA,IL-10,and GAP43(P＜0.05).Conclusions TST could alleviate cognitive impairment through promoting synaptic plasticity and neurovascular unit remodeling in 2-VO model rats,suggesting its significance as a potential drug for apoplexy.

Objective:To evaluate the safety and efficiency of China-made Toumai Robot-assisted laparoscopic radical prosta-tectomy(LRP).Methods:This study included 40 cases of PCa treated from January 2023 to May 2023 by robot-assisted LRP with preservation of the bladder neck and maximal functional urethral length,15 cases with the assistance of Toumai Robot(the TMR group)and the other 25 with the assistance of da Vinci Robot as controls(the DVR group).We recorded the docking time,laparo-scopic surgery time,vesico-urethral anastomosis time,intraoperative blood loss and postoperative urinary continence,and compared them between the two groups.Results:Operations were successfully completed in all the cases.No statistically significant differ-ences were observed between the TMR and DVR groups in the docking time(6 min vs 5 min,P＞0.05)or intraoperative blood loss(200 ml vs 150 ml,P＞0.05).The TMR group,compared with the DVR group,showed a significantly longer median laparoscopic surgery time(146 min vs 130 min,P＜0.05)and median vesico-urethral anastomosis time(19 min vs 16 min,P＜0.05).There were no statistically significant differences between the TMR and DVR groups in the rates of urinary continence recovery immediately af-ter surgery(60.0％[9/15]vs 64.0％[16/25],P＞0.05)or at 1 month(80.0％[12/15])vs(76.0％[19/25],P＞0.05),3 months(93.3％[14/15])vs(92.0％[23/25],P＞0.05)and 6 months postoperatively(100％[15/15])vs(96％[24/25],P＞0.05).Conclusion:China-made Toumai? Robot surgical system is safe and reliable for laparoscopic radical prosta-tectomy,with satisfactory postoperative recovery of urinary continence.

Prostate cancer is a prevalent and debilitating disease that necessitates effective prevention and treatment strategies. Green tea, a well-known beverage derived from the Camellia sinensis plant, contains bioactive compounds with potential health benefits, including catechins and polyphenols. This comprehensive review aims to explore the potential benefits of green tea in prostate cancer prevention and treatment by examining existing literature. Green tea possesses antioxidant, anti-inflammatory, and anti-carcinogenic properties attributed to its catechins, particularly epigallocatechin gallate. Epidemiological studies have reported an inverse association between green tea consumption and prostate cancer risk, with potential protection against aggressive forms of the disease. Laboratory studies demonstrate that green tea components inhibit tumor growth, induce apoptosis, and modulate signaling pathways critical to prostate cancer development and progression. Clinical trials and human studies further support the potential benefits of green tea. Green tea consumption has been found to be associated with a reduction in prostate-specific antigen levels, tumor markers, and played a potential role in slowing disease progression. However, challenges remain, including optimal dosage determination, formulation standardization, and conducting large-scale, long-term clinical trials. The review suggests future research should focus on combinatorial approaches with conventional therapies and personalized medicine strategies to identify patient subgroups most likely to benefit from green tea interventions.
Humans ; Male ; Prostatic Neoplasms/drug therapy* ; Tea/chemistry* ; Catechin/pharmacology*

OBJECTIVES: To study the effect of ligustrazine injection on mitophagy in neonatal rats with hypoxic-ischemic encephalopathy (HIE) and its molecular mechanism. METHODS: Neonatal Sprague-Dawley rats, aged 7 days, were randomly divided into a sham-operation group with 8 rats, a model group with 12 rats, and a ligustrazine group with 12 rats. The rats in the model group and the ligustrazine group were used to establish a neonatal rat model of HIE by ligation of the left common carotid artery followed by hypoxia treatment, and blood vessels were exposed without any other treatment for the rats in the sham-operation group. The rats in the ligustrazine group were intraperitoneally injected with ligustrazine (20 mg/kg) daily after hypoxia-ischemia, and those in the sham-operation group and the model group were intraperitoneally injected with an equal volume of normal saline daily. Samples were collected after 7 days of treatment. Hematoxylin and eosin staining and Nissl staining were used to observe the pathological changes of neurons in brain tissue; immunohistochemical staining was used to observe the positive expression of PINK1 and Parkin in the hippocampus and cortex; TUNEL staining was used to measure neuronal apoptosis; Western blotting was used to measure the expression levels of the mitophagy pathway proteins PINK1 and Parkin and the autophagy-related proteins Beclin-1, microtubule-associated protein 1 light chain 3 (LC3), and ubiquitin-binding protein (P62). RESULTS: Compared with the sham-operation group, the model group had a significant reduction in the number of neurons, an increase in intercellular space, loose arrangement, lipid vacuolization, and a reduction in Nissl bodies. The increased positive expression of PINK1 and Parkin, apoptosis rate of neurons, and protein expression levels of PINK1, Parkin, Beclin1 and LC3 (P<0.05) and the decreased protein expression level of P62 in the hippocampus were also observed in the model group (P<0.05). Compared with the model group, the ligustrazine group had a significant increase in the number of neurons with ordered arrangement and an increase in Nissl bodies, significant reductions in the positive expression of PINK1 and Parkin, the apoptosis rate of neurons, and the protein expression levels of PINK1, Parkin, Beclin1, and LC3 (P<0.05), and a significant increase in the protein expression level of P62 (P<0.05). CONCLUSIONS Ligustrazine can alleviate hypoxic-ischemic brain damage and inhibit neuronal apoptosis in neonatal rats to a certain extent, possibly by inhibiting PINK1/Parkin-mediated autophagy.
Rats ; Animals ; Hypoxia-Ischemia, Brain/metabolism* ; Animals, Newborn ; Rats, Sprague-Dawley ; Beclin-1 ; Autophagy ; Ubiquitin-Protein Ligases/metabolism* ; Protein Kinases/metabolism*