1.Application of proteomics in research for gastrointestinal tumors
Hongqing ZHUO ; Hui ZHANG ; Shan WANG
International Journal of Surgery 2012;39(3):196-199
Proteomics is a technology to study all the proteins encoded by gene.It has become a useful tool for analyzing the expression changes of proteins,and has been widely used in research of gastrointestinal tumors in recent years.Through kinds of techniques such as two-dimensional gel electrophoresis,some differentially expressed proteins correlated with patients prognosis were found,which may served as the possible biomarkers of gastroin testinal tumors in future.It helped to find some certain proteins related to tumor cell nutritional intake,cell metabolism,cell adhesion,cell migration and cytoskeleton remodeling which may play the important roles in development of gastrointestinal tumor.It also helped to explain the drug resistance mechacism of chemotherapy and molecular targeted theraphy for gastrointestinal tumors.Proteomics technology plays an increasingly important role in the basic research and clinical services for gastrointestinal tumors.
2.The correlation between the status of circumferential resection margin and the prognosis of patients With middle and lower rectal carcinoma
Hongqing ZHUO ; Yanbing ZHOU ; Lili LI ; Liang LU ; Wenyi YANG ; Yuyun LI
Chinese Journal of General Surgery 2009;24(2):96-99
Objective To study the relationship between circumferential resection margin status and prognosis of patients with middle and lower rectal cancer.Methods Specimens from 49 patients with middle and lower rectal cancer undergoing total mesorectal excision were studied by the large slice pathologic technique.The local recurrence,metastasis and five-year survival rate were evaluated by Kaplan-Meier Survival analysis.The related clinicopathologic factors were also analyzed.Results The cancer involvement rate of the circumferential resection margins was 24%(12/49).The overall local recurrence rate was 12%(6/49),the distant metastasis and recurrence rate was 27%(13/49),and the five-year survival rate was 67%(33/49).For the 12 patients in which the eircumferential resection margin was tumor positive.the local recurrence rate was 33%compared with 5%in those with negative circumferential resection margin(X2=6.577,P=0.010),distant recurrence was 50%compared with 19%in those with tumor negative margin(X2=4.491,P=0.034).Kaplan-Meier survival analysis showed that patient's survival time was statistically correlative with the circumferential resection margin status(log-rank.P=0.009).Five-year survival rate was 33%in patients with positive circumferential resection margin,compared with 78%in those with negative margins.Tumor diameter(X2=4.451,P=0.035),T staging (X2=20.283,P=0.000),N staging(X2=7.773,P=0.018),the distance away from the anocutaneous line(X2=6.502,P=0.04),tumor location(X2=4.421,P=0.035)and operation type(X2=5.754,P=0.016)were significantly correlated with the circumferential resection margin status of the middle and lower rectal cancer.Conclusions The circumferential resection margin status was an important predictor of local and distant recurrence as well as survival of patients with middle and lower rectal carcinoma.and the status is significantly correlated with tumor diameter,T staging,N staging,the distance away from the anocutaneous line,tumor location and operation type.
3.Changes of content of monoamine neurotransmitters and expression of neurotrophic factors in brain regions of rat models of anxious depression
Hongqing ZHAO ; Yuanshan HAN ; Zhuo LIU ; Qing DU ; Qin YANG ; Pan MENG ; Hui YANG ; Yuhong WANG
Acta Laboratorium Animalis Scientia Sinica 2017;25(4):373-379
Objective To study the content of monoamine neurotransmitters and neurotrophic factor in the hippocampus, amygdala and prefrontal cortex in anxious depression rats, and explore the possible pathogenesis.Methods 60 SD rats were randomly divided into normal group, vehicle group, anxiety group, depression group, and anxious depression group, 12 rats in each group.Chronic restraint stress combined with corticosterone injection was used to establish anxiety and depression model, the modeling time was 21 d.After modeling, elevated plus maze test, open field test, and forced swimming test were used to evaluate the anxiety and depression-like behavior, HPLC-ECD was used to detect the content of 5-HT, NE, and DA in the hippocampus, amygdala, and prefrontal cortex of rats.Western-blotting was used to detect the expression of BDNF and NT-3 in rats.Results Rats in anxious depression model group were comparable to the anxiety group in time and frequency entering open arm time, and number of locomotor activity in open field, and it had a significant difference when compared with the control and depression groups (P<0.01 or P<0.05).Immobile time in anxious depression model rats was increased significantly when compared with the control and anxiety groups (P<0.01).Meanwhile, compared with the control group, 5-HT in hippocampus and 5-HT, NE in amygdala or prefrontal cortex were significantly decreased in the depressive rats with anxiety (P<0.01 or P<0.05).Moreover, the content of BDNF and NT-3 was significantly decreased in each brain regions compared with the control group (P<0.01 or P<0.05), and BDNF levels were obviously decreased compared with the anxiety group (P<0.05).Conclusions Rats of anxious depression have significant anxiety and depression-like behaviors.Its mechanism may be associated with the down-regulation of monoamine neurotransmitters and neurotrophic factors BDNF and NT-3 in hippocampus, amygdala, and prefrontal cortex region.
4.Zuogui Jiangtang Jieyu Formula ameliorating hippocampal neuronal apoptosis in diabetic rats with depression by inhibiting JNK signaling pathway
ZHAO Hongqing ; MOU Qingrui ; JIANG Jiaqi ; ZHU Xuan ; LIU Zhuo ; WANG Yuhong
Digital Chinese Medicine 2024;7(2):195-208
Objective:
To investigate the effect of Zuogui Jiangtang Jieyu Formula (左归降糖解郁方, ZJJF) on hippocampal neuron apoptosis in diabetic rats with depression and to ascertain whether its mechanism involves the regulation of JNK signaling pathway.
Methods:
(i) A total of 72 specific pathogen-free (SPF) grade male Sprague Dawley (SD) rats were randomly divided into six groups, with 12 rats in each group: control, model, metformin (Met, 0.18 g/kg) + fluoxetine (Flu, 1.8 mg/kg), and the high-, medium-, and low-ZJJF dosages (ZJJF-H, 20.52 g/kg; ZJJF-M, 10.26 g/kg; ZJJF-L, 5.13 g/kg) groups. All groups except control group were injected once via the tail vein with streptozotocin (STZ, 38 mg/kg) combined with 28 d of chronic unpredictable mild stress (CUMS) to establish diabetic rat models with depression. During the CUMS modeling period, treatments were administered via gavage, with control and model groups receiving an equivalent volume of distilled water for 28 d. The efficacy of ZJJF in reducing blood sugar and alleviating depression was evaluated by measuring fasting blood glucose, insulin, and glycated hemoglobin levels, along with behavioral assessments, including the open field test (OFT), forced swim test (FST), and sucrose preference test
(SPT). Hippocampal tissue damage and neuronal apoptosis were evaluated using hematoxylin-eosin (HE) staining and terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling (TUNEL) staining. Apoptosis-related proteins Bax, Bcl-2, caspase-3, and the expression levels of JNK/Elk-1/c-fos signaling pathway were detected using Western blot and real-time quantitative polymerase chain reaction (RT-qPCR). (ii) To further elucidate the role of JNK signaling pathway in hippocampal neuronal apoptosis and the pharmacological effects of ZJJF, an additional 50 SPF grade male SD rats were randomly divided into five groups, with 10 rats in each group: control, model, SP600125 (SP6, a JNK antagonist, 10 mg/kg), ZJJF (20.52 g/kg), and ZJJF (20.52 g/kg) + Anisomycin (Aniso, a JNK agonist, 15 mg/kg) groups. Except for control group, all groups were established as diabetic rat models with depression, and treatments were administered via gavage for ZJJF and intraperitoneal injection for SP6 and Aniso for 28 d during the CUMS modeling period. Behavioral changes in rats were evaluated
through the OFT, FST, and SPT, and hippocampal neuron damage and apoptosis were observed using HE staining, Nissl staining, TUNEL staining, and transmission electron microscopy (TEM). Changes in apoptosis-related proteins and JNK signaling pathway in the hippocampal tissues of rats were also analyzed.
Result:
(i) ZJJF significantly reduced the high blood glucose, insulin, and glycated hemoglobin levels in model rats (P < 0.01). It increased autonomous activity and decreased despair-like behaviors (P < 0.01), improved the pathological damage of hippocampal neurons,increased the number of neuronal nuclei (P < 0.01), and red uced the number of mechanocytes, vacuolar cells, and apoptotic neurons (P < 0.05, P < 0.01, and P < 0.01, respectively). ZJJF down-regulated the expression levels of pro-apoptotic proteins Bax and caspase-3 (P < 0.01), up-regulated the anti-apoptotic protein Bcl-2 (P < 0.01), and significantly inhibited the overexpression of phosphorylated JNK (p-JNK), Elk-1, and c-fos (P < 0.01). (ii) SP6 increased autonomous activity and reduced despair time in model rats (P < 0.05), although it had no significant effects on sucrose preference (P > 0.05). It increased the number of Nissl bodies in hippocampal neurons (P < 0.01), reduced the protein expression levels of Bax (P < 0.01) and caspase-3 (P < 0.05), and decreased the number of apoptotic neurons (P < 0.05). SP6 also increased the expression level of Bcl-2 (P < 0.01), and inhibited the high expression levels of p-JNK, Elk-1, and c-fos (P < 0.01, P < 0.01, and P < 0.05, respectively), suggesting that hippocampal neuronal apoptosis in diabetic rats with depression is associated with abnormal activation of JNK signaling pathway. Compared with ZJJF group, ZJJF + Aniso group showed a decrease in sucrose preference (P < 0.05) and an increase in despair time (P < 0.01) with more notable hippocampal neuronal damage. This group also exhibited a decrease in expression level (P < 0.01) Bcl-2 and an increase in expression levels of Bax, caspase-3, p-JNK, Elk-1, and c-fos (P < 0.01, P < 0.05, P < 0.05, P < 0.01, and P < 0.05, respectively), indicating that the antidepressant effects of ZJJF, its improvement of neuronal apoptosis, and regulation of JNK signaling molecules could all be reversed by a specific JNK agonist.
Conclusion
ZJJF exerts a significant hypoglycemic effect and ameliorates the apoptosis of hippocampal neurons by inhibiting the activation of JNK signaling pathway, which is a promising formula for the treatment of diabetic depression in clinical settings.