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Objective:To evaluate the relationship between hippocampal receptor-interacting protein kinase-1 (RIPK1) and nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasomes in postoperative neurocognitive dysfunction of aged rats with chronic knee arthritis pain.Methods:Sixty-four healthy male Sprague-Dawley rats, aged 18 months, weighing 500-550 g, were divided into 4 groups ( n=16 each) using a random number table method: chronic knee arthritis pain group (group P), chronic knee arthritis pain+ operation group (group PS), RIPK1 inhibitor necrostatin-1+ chronic knee arthritis pain+ operation group (group NPS), and DMSO+ chronic knee arthritis pain+ operation group (group DPS). The knee arthritis model was prepared by intra-articular injection of monosodium iodoacetate (MIA) 1 mg into the left knee joint, and 12 weeks later exploratory laparotomy was performed under sevoflurane anesthesia. Necrostatin-1 6.25 mg/kg and the equal volume of DMSO were intraperitoneally injected at 1 h before operation in NPS group and DPS group, respectively. Thermal pain threshold was measured at 1 week before MIA injection and 6 and 12 weeks after MIA injection. Morris water maze test was used to evaluate the cognitive function at 7 days after surgery. Hippocampal tissues were obtained for microscopic examination of the pathological changes (after HE staining) and for determination of the expression of RIPK1, phosphorylated RIPK1 (p-RIPK1), NLRP3, activated cysteine-aspartic protease caspase-1 (cl-caspase-1), apoptosis-associated speck-like protein containing a CARD (ASC) (by Western blot) and contents of interleukin-1beta (IL-1β) and IL-18 (by enzyme-linked immunosorbent assay). Results:Thermal pain threshold was significantly decreased at 6 and 12 weeks after MIA injection as compared with that before injection ( P<0.05), and there was no significant difference in thermal pain threshold among the four groups ( P>0.05). Compared with P group, the escape latency was significantly prolonged, the time of staying at the original platform quadrant was shortened, the number of crossing the original platform was reduced, the expression of RIPK1, p-RIPK1, NLRP3, cl-caspase-1 and ASC was up-regulated, and the contents of IL-1β and IL-18 were increased ( P<0.05), and pathological changes of hippocampal neurons were marked in PS group, DPS group and NPS group. Compared with PS group and DPS group, the escape latency was significantly shortened, the time of staying at the original platform quadrant was prolonged, the number of crossing the original platform was increased, the expression of RIPK1, p-RIPK1, NLRP3, cl-caspase-1 and ASC was down-regulated, the contents of IL-1β and IL-18 were decreased ( P<0.05), and pathological changes of hippocampal neurons were significantly attenuated in NPS group. Conclusions:Postoperative hippocampal RIPK1 function is enhanced in aged rats with chronic knee arthritis pain, which then activates NLRP3 inflammasomes, triggering neuroinflammation, and this process may be involved in the mechanism of postoperative neurocognitive dysfunction.
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Objective @#To investigate the effect of isoprene cysteine carboxymethyltransferase (ICMT) gene on the migration and invasion of salivary adenoid cystic cancer cells (SACC) and the related mechanism, to provide experimental evidence for molecular targeted therapy of SACC.@*Methods@# Adenoid cystic cancer cells SACC-LM and SACC-83 were cultured in vitro, and siRNA was transfected into human SACC-LM and SACC-83 cells (experimental group) by transient transfection of a liposome vector. A blank control group and negative control group were set up respectively (transfected NC-siRNA). qRT-PCR was peformed to measure the mRNA expression of ICMT and RhoA in each group after transfection and to determine the silencing efficiency. The expression of ICMT, membrane RhoA, total RhoA, matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9) and Rho associated with coiled helical binding protein kinase 1 (ROCK1) in each group was detected by Western blot. The proliferation abilityies of SACC cells was detected by CCK-8 assay. The migration and invasion ability of SACC cells were detected by comparing the relative healing area of cell scratch assay and the number of Transwell assay cells. @*Results@#After transfection of ICMT-siRNA into SACC-LM and SACC-83 cells, the expression of ICMT gene and protein in the experimental group was significantly decreased compared with the negative control group and blank control group (P<0.05), but there were no significant differences in the expression of RhoA gene and total protein among all groups (P>0.05). The expression of RhoA membrane proteins, ROCK1, MMP-2, MMP-9 in the experimental group was significantly decreased compared with that in the negative control group and blank control group (P<0.05). Cell proliferation ability was significantly decreased (P<0.05). The migration and invasion abilities were significantly decreased (P<0.05). @*Conclusion @#In vitro silencing of ICMT gene can effectively inhibit the migration and invasion of human SACC-LM and SACC-83 cells, and the mechanism may be related to RhoA-ROCK signaling pathway.
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Objective To research the toxicity of ethanol extracts from Poylgonum multiflorum Thunb(PMT)induced by en?dotoxin of Gram-negative bacteria lipopolysaccharide(LPS)in rat liver,and then investigate the hepatotoxicity mechanisms of PMT on immune inflammatory signal pathway Toll-Like receptor 4(TLR4)-interferon regulated factor3(IRF-3). Methods SD rats were randomly assigned into normal control,LPS(4 mg/kg),acetaminophen APAP(625 mg/kg),PMT 6 g/kg(PMT-L),PMT 12 g/kg (PMT-H),LPS+APAP and LPS+PMT-L/-H groups. The 4 groups later were injected LPS 4 mg/kg by caudal vein,after 2 h,the corre?sponding drugs were administered once a day for 7 consecutive days,respectively. The changes of weight of rats were observed every day. The tissue morphology of liver tissue of rats on 2 h,14 h,5 d,8 d after administration were detected by hematoxylin-eosin stain? ing respectively. Real time quantitative PCR(RT-qPCR)method and Western blotting were used to detect the expression of TLR4, TRIF and IRF3 in the TLR4 signaling pathway in liver cells. Results Two hours after the rat tail vein injection of LPS,the liver tiny granulomas of rats could be observed in LPS-induced groups,and then,the liver injury of rats in LPS group was gradually recovered. Eight Days after LPS induction,the liver tissue structure of rats in LPS group was clear and complete,but in LPS+APAP group and LPS+PMT 6 or 12 g/kg groups,the focal necrosis of hepatocytes,with inflammatory cell infiltration could be observed. The results of RT-qPCR and Western blotting showed that in oral administration of PMT groups,the expression of TLR4,TRIF and IRF-3 mRNA and protein in the liver cells had no significant change compared with the normal control group. But in 4 groups induced with LPS,the expression of TLR4, TRIF and IRF-3 mRNA and protein in the liver cells were significantly higher than that of the normal control group and LPS group(P<0.05). Conclusion PMT can cause liver damage induced by LPS,the hepatotoxicity is related to the positive regulation of TLR4/IRF-3 signaling pathways,which is not related to the dosage of PMT. The results show that activating TLR4/IRF3 signaling pathway is one of the mechanisms of liver injury of PMT in rats induced by LPS.
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OBJECTIVE:To provide reference for promoting the prior usage of essential medicines and scientifically selecting of antitumor medicines in the national and local drug reimbursement list. METHODS:Entering the Human Resources and Social Se-curity Bureau websites in 10 cities(Beijing,Shanghai,Guangzhou,Nanjing,Wuhan,Xi’an,Chengdu,Shenyang,Jinan and Gui-yang),drug reimbursement list was downloaded to statistically analyze the containing of antitumor medicines(including 24 essential medicines). RESULTS:In antitumor medicines,there were 5 cities with more than 100 varieties,of which Shanghai had 255 vari-eties,which was far more than other cities;the numbers of medicines in class A were near 30 in all the cities except Beijing(67 va-rieties),and the number of class B was highest in Shanghai and lowest in Beijing. All the drug reimbursement lists in 10 cities con-tained 24 antitumor essential medicines,however,the classification was different according to the dosage forms,among which, parts of formulations of cytarabine(injections),doxorubicin(injections),busulfan (often release oral dosage forms),fluorouracil (often release oral dosage forms,injections),cyclophosphamide(often release oral dosage forms,injections),methotrexate(often release oral dosage forms,injections)and cisplatin were classified as class A medicines in all cities;oxaliplatin(injections)and pa-clitaxel (injections) were classified as class B medicines;busulfan,fluorouracil,cyclophosphamide and methotrexate were classi-fied as class B in Shanghai only. CONCLUSIONS:There are some differences in the distribution of antitumor essential medicines in drug reimbursement list in each city,the varieties in developed cities are relatively more,and developing cities are less. It is sug-gested to consider the tumor epidemiology characteristics and economic situations,reasonably select antitumor essential medicines into drug reimbursement list and reasonably adjust the proportion of class A and B to ensure the basic medication and drugs’reim-bursement.
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Os autores traçam uma história dos conceitos de contratransferência e de revêrie desde suas introduções, associando-os aos novos conceitos psicanalíticos correlatos que foram sendo introduzidos e exigiram sua redefinição. Em seguida descrevem o processo que permeia a constituição da contratransferência e, sobretudo, o papel da evocação. Sonhos, narrativas e suas expressões atuadas evocam em nós metáforas que combinam articulações discursivas e não discursivas que dão forma aos sentimentos que estão sendo projetados em nós na transferência. Nós, ao interpretarmos, colocamos essas experiências evocadas numa outra base simbólica, ou seja, transmutamos a linguagem evocativa dos símbolos visuais do sonho ou das metáforas, ou ainda das vivências expressivas da contratransferência, em linguagem verbal descritiva de significados e, desta maneira, ampliamos a capacidade de pensar a experiência ao atribuirmos significado aos sentimentos envolvidos. Os trabalhos de Ogden sobre revêrie são discutidos e considerados seminais na elaboração do conceito de revêrie da forma como o utilizamos hoje.
The authors thread a story of the concepts of countertransference and reverie, since the beginning of their use, associating them to new correlated psychoanalytic notions which were gradually introduced and which demanded the redefinition of these original concepts. Next, they describe the process which permeates the constitution of countertransference and, above all, the role of evocation. Dreams, narrations and their expressions evoke in us metaphors, which combine discursive and non-discursive articulations, which in turn give shape to the feelings which are being projected in us during transference. As we interpret, we place these evoked experiences on another symbolic base, transforming the evocative language of the visual symbols of the dream or metaphor, or yet of the expressive occurrences of countertransference, into a verbal language descriptive of meanings. As such, we amplify the capacity of reflecting upon the experience by attributing meaning to the feelings involved. The works of Ogden on reverie are discussed and considered primary to the elaboration of the concept in the way it is used today.
Los autores trazan una historia de los conceptos de contratransferencia y de revêrie desde que fueron introducidos asociándolos a los nuevos conceptos psicoanalíticos relacionados que fueron siendo introducidos y exigieron su redefinición. A continuación describen el proceso que permea la constitución de la contratransferencia y sobre todo el papel de la evocación. Sueños, narraciones y expresiones actuadas nos evocan metáforas que combinan articulaciones discursivas y no discursivas que dan forma a los sentimientos que están siendo proyectados en nosotros durante la transferencia. Nosotros al interpretar, colocamos estas experiencias evocadas, en otra base simbólica, es decir, transmutamos el lenguaje evocador de los símbolos visuales del sueño o de las metáforas o incluso de las vivencias expresivas de la contratransferencia, en un lenguaje verbal descriptivo de significados y de esta forma ampliamos la capacidad de pensar en la experiencia al atribuir significado a los sentimientos involucrados. Los trabajos de Ogden sobre revêrie son discutidos y considerados fundamentales en la elaboración de los conceptos de revêrie de la forma como los utilizamos hoy.