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1.
Braz. J. Pharm. Sci. (Online) ; 58: e18807, 2022. graf
Article in English | LILACS | ID: biblio-1364413

ABSTRACT

Abstract This study aimed to investigate possible changes in the spatial memory of rats and the expression or activity of EGR-1, c-Fos, PKA, and PKC after propofol anesthesia. Thirty-six Sprague-Dawley rats aged 20 months and 36 Sprague-Dawley rats aged three months were each randomly divided into three groups: the control group, the Morris Water Maze (MWM) group, and the propofol group. In the propofol groups of both young and aged rats, the rats were anesthetized by propofol for two or four hours and then performed the MWM test two days or two weeks after anesthesia to assess cognitive function. EGR-1, c-Fos, PKA, and PKC expressions in the rat hippocampus were determined via immunohistochemistry. For the older rats, the escape latency in the P4h/2d group was significantly prolonged (P < 0.05), and the learning curve was right-shifted in the P4h/2w group (P < 0.05). The expression levels of EGR-1, c-Fos, PKA, and PKC in the MWM groups were significantly higher than those in the control groups (P < 0.05). In the P4h/2d group of aged rats, the expression levels of both PKA and PKC were decreased compared with those of the MWM groups. The decreased expression of both protein kinases may be responsible for the observed impairment after propofol anesthesia


Subject(s)
Animals , Male , Female , Rats , Propofol/pharmacology , Rats, Sprague-Dawley/classification , Morris Water Maze Test , Anesthesia/adverse effects , Cognition/classification , Cognitive Dysfunction/pathology , Spatial Memory , Hippocampus
2.
Acta Pharmaceutica Sinica B ; (6): 309-321, 2021.
Article in English | WPRIM | ID: wpr-881138

ABSTRACT

Cullin-RING ligases (CRLs) recognize and interact with substrates for ubiquitination and degradation, and can be targeted for disease treatment when the abnormal expression of substrates involves pathologic processes. Phosphorylation, either of substrates or receptors of CRLs, can alter their interaction. Phosphorylation-dependent ubiquitination and proteasome degradation influence various cellular processes and can contribute to the occurrence of various diseases, most often tumorigenesis. These processes have the potential to be used for tumor intervention through the regulation of the activities of related kinases, along with the regulation of the stability of specific oncoproteins and tumor suppressors. This review describes the mechanisms and biological functions of crosstalk between phosphorylation and ubiquitination, and most importantly its influence on tumorigenesis, to provide new directions and strategies for tumor therapy.

3.
Article in Chinese | WPRIM | ID: wpr-880793

ABSTRACT

OBJECTIVE@#To investigate the effect of miR-324-5p on the proliferation of rat glomerular mesangial (HBZY-1) cells and the role of Syk/Ras/c-fos signaling pathway in mediating this effect.@*METHODS@#HBZY-1 cells cultured in vitro were transiently transfected with miR-324-5p mimics or miR-324-5p-mimics-NC followed by treatment with lipopolysaccharide (LPS). MTT assay was used to detect the proliferation activity of HBZY-1 cells, and RT-qPCR was used to detect the expressions of miR-324-5p and the mRNA expressions of Syk, Ras, MEK1/2, ERK1/2 and c-fos mRNA. The protein expressions of p-Syk, Ras, p-MEK1/2, p-ERK1/2 and c-Fos were detected by Western blotting and immunofluorescence assay.@*RESULTS@#MTT assay showed that exposure to LPS significantly enhanced the proliferative activity of HBZY-1 cells. Compared with the cells treated with LPS and LPS + mimics NC, the cells transfected with miR-324-5p mimics prior to LPS exposure exhibited significantly lowered proliferative activity. Transfection with miR-324-5p mimics significantly lowered the mRNA expressions of Syk, Ras, MEK1/2, ERK1/2 and c-fos and the protein expressions of p-Syk, Ras, MEK1/2, ERK1/2 and c-Fos (@*CONCLUSIONS@#miR-324-5p can inhibit the proliferation of rat chronic glomerulonephritis cells induced by LPS by inhibiting Syk/Ras/c-fos signaling pathway and may potentially serve as a diagnostic indicator and a therapeutic target for chronic glomerulonephritis.


Subject(s)
Animals , Cell Proliferation , Lipopolysaccharides , Mesangial Cells , MicroRNAs/genetics , Proto-Oncogene Proteins c-fos , Rats , Receptor Protein-Tyrosine Kinases , Signal Transduction , ras Proteins
4.
Article in Chinese | WPRIM | ID: wpr-845213

ABSTRACT

Objective: To investigate analgesic effect of gabapentin(GBP)combined with agmatine(AGM)on diabetic neuropathic pain(DNP)model rats and explore possible mechanism. Methods: SPF SD male rats were injected intraperitoneally with STZ 65 mg/kg to create a neuropathic pain model of diabetic rats. The model rats were randomly divided into 5 groups(n=8): the model group, low-dose GBP group(30 mg/kg, ip), high-dose GBP group(100 mg/kg, ip), AGM group(80 mg/kg, ig)and the GBP-AGM combined group(GBP 30 mg/kg, ip+AGM 80 mg/kg, ig). In addition, a control group was set with 8 randomly selected normal rats. The control group and the model group were intragastrically and intraperitoneally administered an equal volume of physiological saline, respectively, while the test groups were administered drugs with the given dose in the indicated manner, all for continuous 14 days. The rat body mass, tail vein blood glucose, mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL) were measured on day 1 before STZ injection and every 7th day after STZ injection, and the plantar tenderness meter was used for the MWT and TWL measurement. The rats were sacrificed 24 h after the last administration, and the spinal cord tissues were harvested. Western blotting was used to detect the expression of p-ERK and c-Fos protein in spinal cord tissues. Results: Compared with the normal control group, the body mass was reduced, blood glucose increased, MWT decreased, and TWL shortened in the model group, all significantly(P0.05)in all of the drug-test groups, while the MWT was increased and the TWL was prolonged in the GBP 100 mg/kg group and the GBP-AGM combined group(both P<0.01). Western blotting results showed that the level of p-ERK and c-Fos protein in the spindal cord was significantly higher in the model group than in the control group(P<0.05). Further, the p-ERK and c-Fos protein level was significantly lower in the GBP+AGM combined group than in the model group(P<0.05)and there was no statistical difference between the GBP 100 mg/kg group and the GBP-AGM combination group. Conclusion: The combination of GBP 30 mg/kg with AGM 80 mg/kg could alleviate neuropathic pain in diabetic rats, which is similar to GBP 100mg/kg and the analgesic effect is likely related to the inhibition of ERK/c-Fos signaling pathway in the spina cord.

5.
Article in Chinese | WPRIM | ID: wpr-872869

ABSTRACT

Objective:To explore the effect of anemarrhena asphodeloside BⅡ (TBⅡ) on the expressions of nuclear transcription factor-κB receptor activator factor ligand (RANKL), RANK and C-FOS genes during osteoclast differentiation. Method:Molecular docking software LeDock was used to score the docking of TBⅡ with RANKL, RANK and C-FOS. RAW264.7 was treated with soluble RANKL(sRANKL) and divided into control group, sRANKL group (model group), Icariin (Ica) group, low-dose TBIⅡ group (2 μmol·L-1), medium-dose TBⅡ group (4 μmol·L-1), and high-dose TBⅡ group (8 μmol·L-1). The corresponding kit was used to detect iconic enzyme (TRAP) of osteoclast differentiation. Total RNA was extracted by trizol method, Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) was used to detect the expressions of C-FOS, upstream RANKL/RANK and downstream nuclear factor of activated T-cells cytoplasmic 1 (NFATC1), and osteoprotegerin OPG. Result:The molecular docking score were -11.86, -11.38, -12.34 kcal·mol-1, and there might be multiple binding sites between TBII as well as RANKL, RANK and C-FOS. Compared with the control group, the content of TRAP in model group increased significantly (P<0.01), and compared with model group, the content of TRAP in each administration group decreased significantly (P<0.01), and TBⅡ decreased the content of TRAP in a dose-dependent manner. Compared with the control group, the expressions of RANKL, RANK, C-FOS and NFATC1 increased (P<0.01), whereas the expression of OPG decreased (P<0.01) in model group. Compared with model group, the expressions of RANKL, RANK, C-FOS and NFATC1 decreased (P<0.01), while the expression of OPG increased (P<0.01) in each administration group. Conclusion:TBⅡ may inhibit the differentiation of osteoclast precursors into osteoclasts, inhibit osteoclast activity, reduce bone resorption and improve osteoporosis by regulating RANKL/RANK/C-FOS signal pathway.

6.
J Biosci ; 2019 Dec; 44(6): 1-8
Article | IMSEAR | ID: sea-214216

ABSTRACT

Limitation in the number of insulin-producing pancreatic b-cells is a typical feature of diabetes. It has been indicated thatactivating pancreatic transcription factors can promote the transformation of hepatocytes into insulin-secreting b-like cells,indicating that direct hepatocyte differentiation seems promising as a treatment for diabetes. Nevertheless, the reprogramming efficiency still remains low. Our previous study found that the expression of c-fos-induced growth factor (FIGF)was increased in the pancreatic tissues in partial pancreatectomy mice compared to that in normal mice. Here, we observedthat treatment with Ad-FIGF was found to enhance MafA and Ngn3-induced reprogramming of BNL CL.2 cells to b-likecells with the ability of secreting insulin. And FIGF overexpression increased the levels of histone H3/H4 acetylation atMafA and Ngn3 promoter regions in BNL CL.2 cells. Importantly, in vivo study further confirmed that forced expression ofFIGF facilitated the insulin expression and decreased the blood glucose levels in STZ mice. These results strengthen thepossibility of developing cell-based therapies for diabetes through utilizing b-like cells derived from non-insulin-secretingcells.

7.
Neuroscience Bulletin ; (6): 369-377, 2019.
Article in English | WPRIM | ID: wpr-775470

ABSTRACT

Immediate-early genes (IEGs) have long been used to visualize neural activations induced by sensory and behavioral stimuli. Recent advances in imaging techniques have made it possible to use endogenous IEG signals to visualize and discriminate neural ensembles activated by multiple stimuli, and to map whole-brain-scale neural activation at single-neuron resolution. In addition, a collection of IEG-dependent molecular tools has been developed that can be used to complement the labeling of endogenous IEG genes and, especially, to manipulate activated neural ensembles in order to reveal the circuits and mechanisms underlying different behaviors. Here, we review these techniques and tools in terms of their utility in studying functional neural circuits. In addition, we provide an experimental strategy to measure the signal-to-noise ratio of IEG-dependent molecular tools, for evaluating their suitability for investigating relevant circuits and behaviors.


Subject(s)
Animals , Brain , Metabolism , Gene Expression Profiling , Methods , Genes, Immediate-Early , Humans , Molecular Imaging , Methods , Neural Pathways , Metabolism , Neurons , Metabolism , Signal-To-Noise Ratio
8.
Chinese Pharmacological Bulletin ; (12): 1357-1363, 2019.
Article in Chinese | WPRIM | ID: wpr-857119

ABSTRACT

Aim To investigate the anti-neuropathic pain effect of DXL-A-22 and further to explore the potential mechanisms. Methods The anti-neuropathic pain effect was evaluated by chronic constriction injury (CCI) model. The potential anti-neuropathic pain mechanisms of DXL-A-22 was studied by Western blot and qPCR. The acute toxicity was evaluated by ultimate test. Results DXL-A-22 (2,1,0. 5 mg . kg-1 ,i. g.) dose-dependently elevated the mechanical withdrawal threshold (MWT) and the paw withdrawal latency (PWL) in CCI rats (P < 0. 05, P < 0. 01), the percentage of pain threshold elevation (PTE%) and the percentage of Maximal Possible Effect (MPE%) was 108%,86%,71% and 77%,56%,43% respectively on day 7 post-operation. DXL-A-22 (2 mg . kg-1 ,i. g.) significantly reduced the expression of p-CaMK II α, p-CREB, p-JAK2, p-STAT3 proteins and TNF-α mRNA, c-Fos mRNA in DRG (P < 0. 05, P < 0.01), and the percent inhibition was 37%, 48%, 35%,58%, 39% and 32% respectively. The expression of TNF-α mRNA and c-Fos mRNA in spinal pord was reduced by 47% and 72% respectively in CCI rats (P <0. 01). Acute toxicity test showed that DXL-A-22 had no obvious toxicity reaction. Conclusions Spirocyclopiperazinium salt compound DXL-A-22 exerts significant antinociceptive effect on CCI model. The anti-neuropathic pain effect of DXL-A-22 may be related to the inhibition of CaMK II α/CREB and JAK2/STAT3 signaling pathways, and the inhibition of the mRNA expression of TNF-α and c-Fos.

9.
Journal of Medical Postgraduates ; (12): 920-925, 2019.
Article in Chinese | WPRIM | ID: wpr-818348

ABSTRACT

Objective The locus coeruleus noradrenergic system regulates the recovery process of general anesthesia, but its mechanism remains unclear. The locus coeruleus has a large amount of projection to the paraventricular nucleus of the thalamus (PVT). This study was to investigate the effect of the α-noradrenergic receptor in PVT neurons in propofol anesthesia. Methods The immunofluorescence technique was used for comparison of the c-fos expression in the PVT neurons collected from male SD rats under propofol anesthesia (the PA group, n = 4) or no anesthesia (the non-PA group, n = 4) and observation of the activity of PVT neurons. PVT microinjection models were established in 40 rats and randomized into four groups of equal number: noradrenaline, phentolamine, propranolol, and isotonic saline. Under propofol anesthesia, the animals received microinjection of noradrenaline, phentolamine, propranolol, and isotonic saline at 1 μL into the PVT, respectively, and were observed for the time of recovery of righting reflex (RORR) and the δ (1-4 Hz), θ (4-8 Hz), α (8-12 Hz), β (12-25 Hz) and γ waves (25-60 Hz) on EEG before and after microinjection. Results The expression of c-fos was significantly reduced in the PA group compared with that in the non-PA control. The Ca2+ signals in the PVT were significantly increased during the propofol induction of the loss of righting reflex (LORR), but decreased in the early stage of and during propofol anesthesia (P < 0.05), and remarkably increased at the emergence of and during RORR (P < 0.05). In comparison with the isotonic saline control, the noradrenaline group showed markedly shortened time of RORR (837.8 s vs 647.7 s, P < 0.05), reduced rate of δ waves (P < 0.05) and elevated rate of β waves (P < 0.05), while the phentolamine group exhibited prolonged time of RORR (837.8 s vs 1045.1 s, P < 0.05) and increased rate of δ waves after microinjection (P < 0.05). Conclusion The α-noradrenergic receptors in PVT neurons play a critical role in promoting recovery from propofol anesthesia.

10.
Article in English | WPRIM | ID: wpr-713688

ABSTRACT

PURPOSE: Benign prostatic hyperplasia (BPH) impacts quality of life in men by causing lower urinary tract symptoms. α1-Adrenoceptor (α1-AR) blockers improve lower urinary tract symptoms. We investigated the efficacy of add-on therapy with α1-AR blockers on BPH rats. METHODS: Rats in the drug-treated groups were orally administered each drug once a day for 30 days after orchiectomy. To induce BPH, rats were castrated and testosterone (20 mg/kg) was injected subcutaneously once per day for 30 days. Cystometry was conducted to measure voiding contraction pressure and the interval contraction time, immunohistochemistry was performed to measure c-Fos and nerve growth factor (NGF) expression in the neuronal voiding centers, and nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry was used to measure nitric oxide synthase (NOS) expression. RESULTS: Orchiectomy and testosterone injection decreased voiding contraction pressure and the interval contraction time, suggesting BPH symptoms. Voiding contraction pressure and the interval contraction time were greater in the group that received the combination treatment (tamsulosin with naftopidil) than in the tamsulosin monotherapy or naftopidil monotherapy groups. c-Fos, NGF, and NOS expression in the neuronal voiding centers was enhanced by BPH induction. c-Fos, NGF, and NOS expression was suppressed by the combination treatment (tamsulosin with naftopidil) to a greater extent than was the case for tamsulosin monotherapy or naftopidil monotherapy. CONCLUSIONS: Combination therapy of tamsulosin and naftopidil showed greater efficacy for the treatment of BPH than tamsulosin monotherapy or naftopidil monotherapy; therefore, combination therapy can be considered as a novel therapeutic method for BPH.


Subject(s)
Animals , Humans , Immunohistochemistry , Lower Urinary Tract Symptoms , Male , Methods , NAD , Nerve Growth Factor , Neurons , Nitric Oxide Synthase , Orchiectomy , Prostatic Hyperplasia , Quality of Life , Rats , Testosterone
11.
Article in Chinese | WPRIM | ID: wpr-709728

ABSTRACT

Objective To evaluate the effects of dexmedetomidine on the expression of c-fos in hippocampus and dentate gyrus in a rat model of endotoxic shock.Methods Thirty-five pathogen-free healthy male Sprague-Dawley rats,aged 3-4 months,weighing 250-300 g,were divided into 5 groups (n =7 each) using a random number table:normal saline group (group NS),dexmedetomidine group (group D),endotoxic shock group (group ES),low-dose dexmedetomidine plus lipopolysaccharide (LPS) group (group LD) and high-dose dexmedetomidine plus LPS group (group HD).Dexmedetomidine 0.5 μg/kg was injected via the tail vein in D and LD groups,and dexmedetomidine 4.5 μg/kg was given in group HD.Normal saline 0.5 ml/kg was injected in NS and ES groups,5 min later normal saline 0.5 ml/kg was injected in NS and D groups and LPS 5 mg/kg was injected in the other groups,and the injection time was 10 min in all groups.Rats were sacrificed at 6 h after LPS injection,brains were removed,and the hippocampus and dentate gyrus were isolated for detection of the expression of c-fos by immunohistochemistry.Results Compared with group NS or group D,the expression of c-fos in the hippocampus and dentate gyrus was significantly up-regulated in group ES (P<0.05).Compared with group LPS,the expression of c-fos in the hippocampus and dentate gyrus was significantly down-regulated in LD and HD groups (P<0.05).Compared with group LD,the expression of c-fos in hippocampal CA1 and CA3 areas was significantly down-regulated in group HD (P<0.05).Conclusion The neuroprotective mechanism of dexmedetomidine is related to inhibiting the up-regulated expression of c-fos in the hippocampus and dentate gyrus in a rat model of endotoxic shock.

12.
Experimental Neurobiology ; : 387-396, 2018.
Article in English | WPRIM | ID: wpr-717413

ABSTRACT

The nucleus accumbens (NAc) is the major component of the ventral striatum that regulates stress-induced depression. The NAc receives dopaminergic inputs from the ventral tegmental area (VTA), and the role of VTA-NAc neurons in stress response has been recently characterized. The NAc also receives glutamatergic inputs from various forebrain structures including the prelimbic cortex (PL), basolateral amygdala (BLA), and ventral hippocampus (vHIP), whereas the role of those glutamatergic afferents in stress response remains underscored. In the present study, we investigated the extent to which descending glutamatergic neurons activated by stress in the PL, BLA, and vHIP project to the NAc. To specifically label the input neurons into the NAc, fluorescent-tagged cholera toxin subunit B (CTB), which can be used as a retrograde neuronal tracer, was injected into the NAc. After two weeks, the mice were placed under restraint for 1 h. Subsequent histological analyses indicated that CTB-positive cells were detected in 170~680 cells/mm² in the PL, BLA, and vHIP, and those CTB-positive cells were mostly glutamatergic. In the PL, BLA, and vHIP regions analyzed, stress-induced c-Fos expression was found in 20~100 cells/mm². Among the CTB-positive cells, 2.6% in the PL, 4.2% in the BLA, and 1.1% in the vHIP were co-labeled by c-Fos, whereas among c-Fos-positive cells, 7.7% in the PL, 19.8% in the BLA, and 8.5% in the vHIP were co-labeled with CTB. These results suggest that the NAc receives a significant but differing proportion of glutamatergic inputs from the PL, BLA, and vHIP in stress response.


Subject(s)
Animals , Basolateral Nuclear Complex , Cholera Toxin , Depression , Hippocampus , Mice , Neurons , Nucleus Accumbens , Prosencephalon , Ventral Striatum , Ventral Tegmental Area
13.
Article in Chinese | WPRIM | ID: wpr-734600

ABSTRACT

Objective To evaluate the effect of intrathecal dexmedetomidine on expression of sub-stance P (SP) and c-fos in the spinal dorsal horns of rats with visceral pain. Methods Thirty-two clean-grade healthy adult male Sprague-Dawley rats, weighing 250-300 g, were divided into 4 groups ( n=8 each) using a random number table method: control group (C group), visceral pain group (VP group), dexmedetomidine group (D group) and dexmedetomidine plus atipamezole group (DA group). VP, D and DA groups received intraperitoneal injection of 0. 9% acetic acid 10 ml∕kg to establish the model of visceral pain, while group C received the equal volume of normal saline instead. At 10 min before the model was es-tablished, dexmedetomidine 20 μl (1μg∕kg) and dexmedetomidine 1μg∕kg plus atipamezole 1μg∕kg (20μl) were intrathecally injected in D and DA groups, respectively, and the equal volume of normal saline 20μl was given instead in C and VP groups. Visceral pain index ( VPI) was recorded at 1 h after intraperito-neal injection, and then rats were sacrificed, and the dorsal horns of the spinal cord ( L4-6 ) were removed for determination of the expression of SP and c-fos by immunohistochemistry. Results Compared with group C, VPI was significantly increased, and the expression of SP and c-fos was up-regulated in VP, D and DA groups (P<0. 05). Compared with group VP, VPI was significantly decreased, and the expression of SP and c-fos was down-regulated in D and DA groups (P<0. 05). Compared with group D, VPI was signifi-cantly increased, and the expression of SP and c-fos was up-regulated in group DA ( P<0. 05) . Conclusion Intrathecal dexmedetomidine reduces the visceral pain through inhibiting the expression of SP and c-fos in the spinal dorsal horns, which is related to the α2-adrenergic receptor in spinal dorsal horns of rats.

14.
Article in Chinese | WPRIM | ID: wpr-806380

ABSTRACT

Objective@#To explore the effect of c-fos on multidrug resistance of laryngeal cancer TU177 cells.@*Method@#Increasing drug concentration gradient is adopted to establish the stability of the laryngeal cancer drug resistance in cell line; RT-PCR and Western blot were used to detect difference of the c-fos between TU177 and TU177/VCR cells; plasmids with human c-fos knockdown or over expression were transfected into TU177/VCR and TU177 cells respectively, and the effects of different treatment on cell proliferation were investigated with MTT.@*Results@#The drug resistance of TU177/VCR cells was 26.25-fold in vincristine (VCR), 7.33-fold in Paclitaxel (TAX), 2.41 in cisplatin (DDP), and 5.50 in 5-fluorouracil (5-FU), comparing with TU177( P<0.05). The TU177/VCR cells had significantly higher c-fos expression compared to TU177 cells( P<0.05). The results showed that the IC50 values of 5-FU for the NC group and c-fos shRNA group were (306.2±6.3)μmol/L and (81.3±3.9)μmol/L, respectively, which was decreased by 73% in the c-fos shRNA group compared to that in the NC group (P<0.05). Similarly, the results showed that the IC50 values for 5-FU were (55.3±9.4) μmol/L in NC group and (288.1±7.3)μmol/L in c-fos WT group, which was increased 5.21-fold in c-fos WT cells.@*Conclusion@#C-fos plays important role in multidrug resistance of larynx cancer cell TU177/VCR, and might become a new molecular target for laryngeal cancer treatment.

15.
Chinese Journal of Anesthesiology ; (12): 1456-1459, 2018.
Article in Chinese | WPRIM | ID: wpr-745630

ABSTRACT

Objective To evaluate the changes in the expression of c-fos protein in the spinal cord in a rat model of oxycodone dependence or withdrawal response.Methods Thirty SPF adult male Sprague-Dawley rats,aged 6-8 weeks,weighing 180-220 g,were divided into 3 groups (n=10 each) using a random number table method:normal saline group (group NS),oxycodone dependence group (group OD),and oxycodone withdrawal group (group OW).In OD and OW groups,oxycodone was injected subcutaneously in back,5 days in total,with the dose of 2,3,4,5 and 6 mg/kg in turn,3 times a day (8:00/15:00/22:00).The equal volume of normal saline was given instead in group NS.The mechanical paw withdrawal threshold was measured at 3 days before administration and 30 min after the last administration every day.The oxycodone withdrawal was induced by intraperitoneal injection of naloxone 4 mg/kg at 8 h after the last administration of oxycodone on 5th day in group OW.The withdrawal response scores and range of weight changes were recorded within 15 min after giving naloxone or normal saline in NS and OW groups.Spinal cord tissues were collected at 1 h after the last administration on 5th day in group OD and at 1 h after giving normal saline or naloxone on 5th day in NS and OW groups for determination of the expression of c-fos protein by Western blot.Results Compared with group NS,the mechanical paw withdrawal threshold was significantly increased on 1 and 2 days after administration,and the expression of c-fos protein in the spinal cord was up-regulated in OD and OW groups,and withdrawal response scores were significantly increased,and the range of weight change was increased in group OW (P<0.05).The expression of c-fos protein was significantly down-regulated in group OW as compared with group OD (P<0.05).Conclusion Oxycodone dependence or withdrawal response may be related to the expression of c-fos protein in the spinal cord of rats,and the expression is up-regulated during oxycodone dependence,while down-regulated during oxycodone withdrawal.

16.
Article in Chinese | WPRIM | ID: wpr-700113

ABSTRACT

Objective:To explore cytotoxicity of Synsepalum dulcificum (S.dulcificum) Daniell (Sapotaceae) on human colon cancer (HCT-116 and HT-29),human monocytic leukemia (THP-1) and normal (HDFn) cell lines,and its effect on the expression of early apoptotic genes,c-fos and c-jun.Methods:Leaf,stem and berry of S.dulcificum were separately extracted by using 2 solvents,10% ethanol (EtOH) and 80% methanol (MeOH).PrestoBlue(R)cell viability assay and qRT-PCR assay were conducted to examine the above objectives respectively.Results:Stem MeOH,stem EtOH,and berry EtOH extracts of S.dulcificum were cytotoxic to HCT-116 and HT-29 human colon cancer cells.For HCT-116,IC50 values of these 3 extracts were not significantly different (P>0.05) from that of the positive control bleomycin (IC5o of 33.57 μg/mL),while for HT-29,IC5o values of these 3 extracts were significantly lower (P<0.05) than that of bleomycin (IC50 of 25.24 μg/mL).None of the extracts were cytotoxic to the THP-1 monocytic leukemia cells and HDFn normal human dermal fibroblasts.For both HCT-116 and HT-29,these extracts significantly up-regulated (P<0.05) the expression of c-fos and c-jun compared to the untreated negative control.Conclusions:The results of this study suggest that cytotoxicity of stem MeOH,stem EtOH,and berry EtOH extracts of S.dulcificum on HCT-116 and HT-29 colon cancer cells is due to the induced apoptosis which is caused by the up-regulation of the expression of early apoptotic genes,c-fos and c-jun.

17.
Article in Chinese | WPRIM | ID: wpr-699833

ABSTRACT

Objective To observe c-Fos expression in visual cortex of infant rhesus monkeys with myopia induced by hyperopic defocus and preliminarily investigate the possibility of visual cortex participating in myopia. Methods Eight SPF grade healthy infant rhesus monkeys aged 20 to 30 days were randomly divided into hyperopic defocused group and control group,4 monkeys for each group. The monkeys in hyperopic defocused group wore -3 D spectacle lenses. The monkeys in control group wore 0 D lenses. The monkeys' refractive error,corneal topography, vitreous chamber depth were measured at the start of lens wear and at 2,4,6,8,12 weeks post-treatment. At 12 weeks post-treatment,the visual cortex tissues were removed for c-Fos protein measurement by immunohistochemistry and Western blot assays. The results were analyzed semiquantitatively to compare the differences of c-Fos expression between hyperopic defocused group and control group. The use and care of the animals complied with Regulations for the Administration of Affair Concerning Experimental Animals by State Science and Technology Commission. This study protocol was approved by Ethic Committee of Zhongshan Ophthalmic Center ( No. 2013-014). Results After 12 weeks'lens wear,the vitreous chamber elongation amplitude of hyperopic defocused group monkeys was more obvious than that of the control group ([0.93±0.24]mm vs. [0.72±0.09]mm;t=2.292,P=0.047). The decrease of hyperopic degrees of hyperopic defocused group monkeys was more obvious than that of the control group ([-3.23± 1.36]D vs. [-1.55±0.52]D;t=-3.273,P=0.006). The eyes of hyperopic defocused group monkeys appeared a remarkable myopic shift after treatment. The number of c-Fos immunoreactive neurons was less in the hyperopic defocused group than that in the control group,with a statistically significant difference between them ([1 843±191]/mm2vs. [2 296±503]/mm2;t=2.381,P=0.041). Western blot assay showed that the optical density of c-Fos protein in the hyperopic defocused group was significantly less than that in the control group (0.50±0.17 vs. 0.99± 0.22;t=-4.982,P<0.01). Conclusions Hyperopic defocus,as an abnormal visual stimulus,can induce the onset of myopia in infant rhesus monkeys and inhibit c-Fos expression in visual cortex. Visual cortex may participate in myopia induced by hyperopic defocus.

18.
Article in Chinese | WPRIM | ID: wpr-693585

ABSTRACT

Objective To observe the effect of Rhy-SLN on the proliferation of rat vascular smooth muscle cells (VSMC) induced by TGF-β1, and explore the mechanism. Methods The primary culture of rat thoracic aortic vascular smooth muscle cells was studied by tissue block culture method. The cells were divided into the control group, TGF-β1 group, TGF-β1+ the high, medium and low dosage groups of Rhy-SLN. In addition to the control group, the cells of the other groups were involved in the intervention of TGF-β1 of 20 g/L, and the high, medium and low dosage groups of Rhy-SLN cells were involved in the intervention of 25, 50, 100 mg/L of the hook teng solid lipid nanoparticles. After 24 hours of culture, MTT assay was used to detect cell proliferation inhibition rate in each group, and the cell cycle was detected by flow cytometry. The expression of c-myc and c-Fos protein in each group was detected by Western blot method. Results Compared with the TGF-β1 group, the absorbance value (0.457 ± 0.046 vs. 0.975 ± 0.049) of TGF-β1+ rhy-sln high dose group significantly decreased (P<0.01); the number of S phase cells (15.87% ± 2.47%, 15.23% ± 1.69%, 17.02% ± 2.87% vs.38.58% ± 2.68%)of TGF-β1+rhy-sln in each dose group significantly decreased(P<0.01);The c-myc(48.65 ±3.65,50.69 ± 4.16,55.29 ± 3.67 vs.68.21 ± 3.25)and c-Fos(38.78 ± 4.25,43.56 ± 3.69,46.58 ± 3.57 vs.66.54 ± 4.09) of the TGF-β1+ rhy-sln each dose group significantly decreased (P<0.01). Conclusions The Rhy-SLN can inhibit the proliferation of VSMC in rats induced by TGF-β1.Its mechanism is related to the conversion of G0/G1 phase to the S phase and the expression of the reduction of c-myc and c-fos protein.

19.
Chinese Herbal Medicines ; (4): 424-430, 2018.
Article in Chinese | WPRIM | ID: wpr-842113

ABSTRACT

Objective: To research the protective effects of different extracts from Compound Houttuyniae Herba (CHH) and its mechanism through JAK/STAT-SOCS-1 signaling pathway. Methods: The normal group comprised db/m mice (n = 8). db/db mice were randomly divided into seven groups with eight mice in each group according to the applied treatment method: model group, metformin hydrochloride (MH) group, AG490 group, water extract (WE) group, ethanol extract (EE) group, volatile oil (VO) group, and mixture (MG) group (mixture of above three extract) of CHH. After 8 weeks, the general status, biochemical indicators, and renal histological changes in the mice were evaluated, the total RNA and protein were collected and RT-PCR method was used to examine the effect on mRNA expression of JAK2, STAT3, SOCS1, and Western blot method was used to detect the protein expression of JAK2, P-JAK2, STAT3, P-STAT3, SOCS1, c-fos, and c-jun. Immunofluorescence was used to observe the protein expression of c-fos and c-jun in kidney tissue. Results: Compared with normal group, the serum level of TGF-β1, FN of EE, VO, and MG groups were decreased (P < 0.05). Renal function was also improved but not significantly. Also, the renal histology was improved especially in the mixture group. The protein expression of JAK2, STAT3, P-JAK2, P-STAT3, and the genetic expression of JAK2 and STAT3 in kidney tissue were significantly increased in the model group (P < 0.05). Compared with the model group, the expression of P-JAK2 and P-STAT3 was down-regulated in treatment groups; The expression of SOCS-1 of VO and mixture groups were elevated (P < 0.05). Conclusion: CHH has beneficial effects on diabetic renal injury, which may protect and improve the kidney function and reduce urinary protein, maintain the integrity of the kidney structure and function.

20.
Article in Chinese | WPRIM | ID: wpr-513505

ABSTRACT

Purpose To investigate the relationship and clinical significance of high-risk human papillomavirus infection and expression of c-jun and c-fos protein in cervical carcinoma.Methods Cervista HR-HPV testing,immunohistochemical SP method were employed to detect the infection of HR-HPV,c-jun and c-fos protein in 70 cases of CSCC,60 cases of cervical intraepithelial neoplasia and 20 cases of chronic cervicitis.The correlation between c-jun and c-fos protein expression and of HR-HPV infection was analyzed.Results Of the 70 cases of CSCC,the positive HR-HPV was 69 cases,the positive rate in HR-HPV in A9 group was the highest (85%,59/69).The positive expression of c-jun and c-fos were 80% (56/70),85.7% (60/70) in 70 cases CSCC,70% (21/30) and 70% (21/30) in 30 cases of cervical high grade intraepithelial neoplasia,and 20% (6/30),23.3% (7/30) in 30 cases cervical low grade intraepithelial neoplasia,but the positive expression rates of c-jun and c-fos in the 20 cases of chronic cervicitis were 0.Expression of c-jun and c-fos in cervical cancer group was higher than that in the chronic cervicitis group and low grade intraepithelial neoplasia (P < 0.05).The expression of c-jun and c-fos was statistically significant in different groups of clinical stage and pathologic grading in the CSCC (P < 0.05).Additionally,the expression of c-jun and c-fos was positively correlated with the infection of HR-HPV in CSCC (P < 0.01).Conclusion The infection of HR-HPV has significant subtype-specific and has a positive correlation with the expression of c-jun and c-fos in CSCC,which suggests that AP-1 pathway activation after HRHPV infection may be associated with the occurrence and development of cervical carcinoma.

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