RESUMO
Synthetic lethality through combinatorial targeting DNA damage response (DDR) pathways provides exciting anticancer therapeutic benefit. Currently, the long noncoding RNAs (lncRNAs) have been implicated in tumor drug resistance; however, their potential significance in DDR is still largely unknown. Here, we report that a human lncRNA, CTD-2256P15.2, encodes a micropeptide, named PAR-amplifying and CtIP-maintaining micropeptide (PACMP), with a dual function to maintain CtIP abundance and promote poly(ADP-ribosyl)ation. PACMP not only prevents CtIP from ubiquitination through inhibiting the CtIP-KLHL15 association but also directly binds DNA damage-induced poly(ADP-ribose) chains to enhance PARP1-dependent poly(ADP-ribosyl)ation. Targeting PACMP alone inhibits tumor growth by causing a synthetic lethal interaction between CtIP and PARP inhibitions and confers sensitivity to PARP/ATR/CDK4/6 inhibitors, ionizing radiation, epirubicin, and camptothecin. Our findings reveal that a lncRNA-derived micropeptide regulates cancer progression and drug resistance by modulating DDR, whose inhibition could be employed to augment the existing anticancer therapeutic strategies.
Assuntos
Endodesoxirribonucleases , Neoplasias , Peptídeos , Poli ADP Ribosilação , RNA Longo não Codificante , Reparo do DNA , Endodesoxirribonucleases/metabolismo , Humanos , Proteínas dos Microfilamentos/genética , Proteínas dos Microfilamentos/metabolismo , Neoplasias/genética , Neoplasias/metabolismo , Peptídeos/farmacologia , Poli Adenosina Difosfato Ribose/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Poli(ADP-Ribose) Polimerases/genética , Poli(ADP-Ribose) Polimerases/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismoRESUMO
B cells possess anti-tumor functions mediated by granzyme B, in addition to their role in antigen presentation and antibody production. However, the variations in granzyme B+ B cells between tumor and non-tumor tissues have been largely unexplored. Therefore, we integrated 25 samples from the Gene Expression Omnibus database and analyzed the tumor immune microenvironment. The findings uncovered significant inter- and intra-tumoral heterogeneity. Notably, single-cell data showed higher proportions of granzyme B+ B cells in tumor samples compared to control samples, and these levels were positively associated with disease-free survival. The elevated levels of granzyme B+ B cells in tumor samples resulted from tumor cell chemotaxis through the MIF- (CD74 + CXCR4) signaling pathway. Furthermore, the anti-tumor function of granzyme B+ B cells in tumor samples was adversely affected, potentially providing an explanation for tumor progression. These findings regarding granzyme B+ B cells were further validated in an independent clinic cohort of 40 liver transplant recipients with intrahepatic cholangiocarcinoma. Our study unveils an interaction between granzyme B+ B cells and intrahepatic cholangiocarcinoma, opening up potential avenues for the development of novel therapeutic strategies against this disease.
Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Transplante de Fígado , Humanos , Granzimas/genética , Colangiocarcinoma/genética , Colangiocarcinoma/cirurgia , Prognóstico , Neoplasias dos Ductos Biliares/genética , Neoplasias dos Ductos Biliares/cirurgia , Ductos Biliares Intra-Hepáticos , Microambiente TumoralRESUMO
It has been shown that prostaglandin (PG) E2 synthesized in the lateral parabrachial nucleus (LPBN) is involved in lipopolysaccharide-induced fever. But the neural mechanisms of how intra-LPBN PGE2 induces fever remain unclear. In this study, we investigated whether the LPBN-preoptic area (POA) pathway, the thermoafferent pathway for feed-forward thermoregulatory responses, mediates fever induced by intra-LPBN PGE2 in male rats. The core temperature (Tcore) was monitored using a temperature radiotelemetry transponder implanted in rat abdomen. We showed that microinjection of PGE2 (0.28 nmol) into the LPBN significantly enhanced the density of c-Fos-positive neurons in the median preoptic area (MnPO). The chemical lesioning of MnPO with ibotenate or selective genetic lesioning or inhibition of the LPBN-MnPO pathway significantly attenuated fever induced by intra-LPBN injection of PGE2. We demonstrated that EP3 receptor was a pivotal receptor for PGE2-induced fever, since microinjection of EP3 receptor agonist sulprostone (0.2 nmol) or EP3 receptor antagonist L-798106 (2 nmol) into the LPBN mimicked or weakened the pyrogenic action of LPBN PGE2, respectively, but this was not the case for EP4 and EP1 receptors. Whole-cell recording from acute LPBN slices revealed that the majority of MnPO-projecting neurons originating from the external lateral (el) and dorsal (d) LPBN were excited and inhibited, respectively, by PGE2 perfusion, initiating heat-gain and heat-loss mechanisms. The amplitude but not the frequency of spontaneous and miniature glutamatergic excitatory postsynaptic currents (sEPSCs and mEPSCs) in MnPO-projecting LPBel neurons increased after perfusion with PGE2; whereas the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) and the A-type potassium (IA) current density did not change. In MnPO-projecting LPBd neurons, neither sEPSCs nor sIPSCs responded to PGE2; however, the IA current density was significantly increased by PGE2 perfusion. These electrophysiological responses and the thermoeffector reactions to intra-LPBN PGE2 injection, including increased brown adipose tissue thermogenesis, shivering, and decreased heat dissipation, were all abolished by L-798106, and mimicked by sulprostone. These results suggest that the pyrogenic effects of intra-LPBN PGE2 are mediated by both the inhibition of the LPBd-POA pathway through the EP3 receptor-mediated activation of IA currents and the activation of the LPBel-POA pathway through the selective enhancement of glutamatergic synaptic transmission via EP3 receptors.
RESUMO
BACKGROUND: How to quickly read and interpret intraoperative ultrasound (IOUS) images of patients with degenerative cervical myelopathy (DCM) to obtain meaningful information? Few studies have systematically explored this topic. PURPOSE: To systematically and comprehensively explore the IOUS characteristics of patients with DCM. MATERIALS AND METHODS: This single-center study retrospectively included patients with DCM who underwent French-door laminoplasty (FDL) with IOUS guidance from October 2019 to March 2022. One-way ANOVA and Pearson's /Spearman's correlation analysis were used to analyze the correlations between the cross-sectional area of the spinal cord (SC) and individual characteristics; the relationships between the morphology, echogenicity, pulsation, decompression statuses, compression types of SC, location of the spinal cord central echo complex (SCCEC) and the disease severity (the preoperative Japanese Orthopedic Association score, preJOA score); the difference of the spinal cord pulsation amplitude(SCPA) and the SCCEC forward movement rate (FMR) between the compressed areas(CAs) and the non-compressed areas (NCAs). RESULTS: A total of 38 patients were successfully enrolled (30 males and 8 females), and the mean age was 57.05 ± 10.29 (27-75) years. The cross-sectional area of the SC was negatively correlated with age (r = - 0.441, p = 0.006). The preJOA score was significantly lower in the heterogeneous group than in the homogeneous group (P < 0.05, p = 0.005). The hyperechoic area (HEA) was negatively while the SCCEC FMR was positively correlated with the preJOA score (r = - 0.334, p = 0.020; r = 0.286, p = 0.041). The SCCEC FMR and SCPA in CAs were significantly greater than those in NCAs (p < 0.05, p = 0.007; P < 0.001, P = 0.000). CONCLUSION: The cross-sectional area of the SC decreases with age in adults. More changes in intramedullary echogenicity and less moving forward of the SCCEC often indicate poor SC status, and the SCCEC FMR and SCPA are more pronounced in CAs.
Assuntos
Vértebras Cervicais , Laminoplastia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Vértebras Cervicais/cirurgia , Vértebras Cervicais/diagnóstico por imagem , Adulto , Laminoplastia/métodos , Doenças da Medula Espinal/cirurgia , Doenças da Medula Espinal/diagnóstico por imagem , Ultrassonografia , Compressão da Medula Espinal/cirurgia , Compressão da Medula Espinal/diagnóstico por imagemRESUMO
Poor selectivity, low bioavailability and serious systemic side-effects have limited the application of traditional chemotherapy method for treatment of prostate cancer. Stimuli-responsive drug delivery systems for chemotherapy are mainly based on the unique characteristics of tumor microenvironment. In this study, the GSH-sensitive poly-TTG-SS@DTX NPs (DTX-loaded poly-Tetraethylene glycol nanoparticles) were designed and synthesized, which were characterized with nanosized diameter (92.8 ± 2.5 nm) and negatively charged surface charge (-24.7 ± 5.56 mV). Experiments in vitro showed that poly-TTG-SS@DTX NPs had good compatibility to healthy cells and strong anti-tumor effect because of rapid and sustained drug release of DTX from poly-TTG-SS@DTX NPs under the tumor-microenvironment condition. The cellular activity remained greater than 90% when the concentration of poly-TTG-SS NPs reached as high as 100 µg/mL treated on healthy cells. The killing effect of DTX loading NPs group on C4-2 cells was stronger than that of free anti-tumor drug and free DTX combined with the blank nano-carrier (25.21% vs 19.93% vs 20.96%). In conclusion, poly-TTG-SS@DTX NPs may provide a new therapeutic strategy for the chemotherapy of prostate cancer.
Assuntos
Neoplasias da Próstata , Microambiente Tumoral , Masculino , Humanos , Neoplasias da Próstata/tratamento farmacológico , Excipientes , Sistemas de Liberação de Medicamentos , Disponibilidade BiológicaRESUMO
In-depth studies of carcass characters and meat quality could provide insight both for breeding improvement and food development in pigs. Breed and gender are two main factors affected the carcass and meat altitude, which plays important roles in pork industry. The aim of this study was to evaluate the sex effects on carcass characteristics and meat quality traits in a novel Duroc strain pig crossbred from French line, American line and Canadian line pigs. A total of 30 pigs (15 surgical-castrated males and 15 females) with similar birthweight (1.8 ± 0.13 kg) was used in experiment. During the experiment period, all pigs were fed same commercial diets. Overall, female pigs observed higher (p < 0.05) carcass weight, slaughter backfat, loin muscle area, loin muscle depth, carcass yield, pH on 45 min, meat histidine and essential amino acid (AA) compositions, and eicosenoic, unsaturation and free fatty acids (FA) compositions compared with meat from castrated males. Whereas, castrated males' meat showed better altitude (p < 0.05) on meat lightness, meat moisture content percentage, total umami AA and stearic acid and saturated FA compositions than those from female ones. In conclusion, the results of this study provide evidence on the sex effects on meat quality and carcass parameters in Duroc strain pigs. Furthermore, this study also give a reference on the relationship between sex and carcass and meat characteristics in Durco strain pigs.
Assuntos
Aminoácidos , Composição Corporal , Animais , Feminino , Masculino , Composição Corporal/fisiologia , Canadá , Ácidos Graxos , Suínos , Carne Vermelha , Análise de AlimentosRESUMO
Super-enhancer (SE) is a cluster of active typical enhancers (TE) with high levels of the Mediator complex, master transcriptional factors, and chromatin regulators. SEs play a key role in the control of cell identity and disease. Traditionally, scientists used a variety of high-throughput data of different transcriptional factors or chromatin marks to distinguish SEs from TEs. This kind of experimental methods are usually costly and time-consuming. In this paper, we proposed a model DeepSE, which is based on a deep convolutional neural network model, to distinguish the SEs from TEs. DeepSE represent the DNA sequences using the dna2vec feature embeddings. With only the DNA sequence information, DeepSE outperformed all state-of-the-art methods. In addition, DeepSE can be generalized well across different cell lines, which implied that cell-type specific SEs may share hidden sequence patterns across different cell lines. The source code and data are stored in GitHub (https://github.com/QiaoyingJi/DeepSE).
Assuntos
Cromatina , Elementos Facilitadores Genéticos , Linhagem Celular , Cromatina/genética , Redes Neurais de Computação , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
BACKGROUND: T cells and B cells play a key role in alloimmune responses. We aimed to characterize the shift of T cell subsets and B cell subsets during acute hepatic rejection, and further determine whether they could serve as a prognostic marker. METHODS: Blood samples together with the clinical data from liver transplant recipients with and without acute hepatic rejection were collected and analyzed as well as from a validation cohort. RESULTS: Upon activation the expression of TGF-ß and granzyme B in CD19+B cells, and the expression of IL-2 and IFN-γ in CD4+T cells were higher in acute hepatic rejection. However, only the frequencies of granzyme B+CD19+B cells and IFN-γ+CD4+T cells correlated with liver function in addition to with each other. A combination of the two cell subsets as a novel marker could classify rejection versus non-rejection (area under the curve 0.811, p = 0.001) with the cut-off value of 62.93%, which was more sensitive for worse histological changes (p = 0.027). Moreover, the occurrence rate of acute rejection was higher in the group with the novel marker > 62.93% (p = 0.000). The role of the novel marker was further confirmed in a validation cohort, which was identified to be the only significant independent risk factor for acute rejection (odds ratio: 0.923; 95% CI confidence interval: 0.885-0.964; p = 0.000). CONCLUSIONS: A combination of the percentages of IFN-γ+CD4+T cells and granzyme B+CD19+B cells can distinguish rejection from non-rejection, which can be used as a potential prognostic marker for acute rejection in liver transplant recipients.
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Linfócitos B , Rejeição de Enxerto , Estudos de Casos e Controles , Granzimas , FígadoRESUMO
Perilla frutescens (L.) Britton is a classic herbal plant used widely against asthma in China. But its mechanism of beneficial effect remains undermined. In the study, the antiallergic asthma effects of Perilla leaf extract (PLE) were investigated, and the underlying mechanism was also explored. Results showed that PLE treatment significantly attenuated airway inflammation in OVA-induced asthma mice, by ameliorating lung pathological changes, inhibiting recruitment of inflammatory cells in lung tissues and bronchoalveolar lavage fluid (BALF), decreasing the production of inflammatory cytokines in the BALF, and reducing the level of immunoglobulin in serum. PLE treatment suppressed inflammatory response in antigen-induced rat basophilic leukemia 2H3 (RBL-2H3) cells as well as in OVA-induced human peripheral blood mononuclear cells (PBMCs). Furthermore, PLE markedly inhibited the expression and phosphorylation of Syk, NF-κB, PKC, and cPLA2 both in vivo and in vitro. By cotreating with inhibitors (BAY61-3606, Rottlerin, BAY11-7082, and arachidonyl trifluoromethyl ketone) in vitro, results revealed that PLE's antiallergic inflammatory effects were associated with the inhibition of Syk and its downstream signals NF-κB, PKC, and cPLA2. Collectively, the present results suggested that PLE could attenuate allergic inflammation, and its mechanism might be partly mediated through inhibiting the Syk pathway.
Assuntos
Asma , Perilla , Animais , Asma/metabolismo , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Inflamação/metabolismo , Leucócitos Mononucleares/metabolismo , Pulmão/metabolismo , Camundongos , NF-kappa B/metabolismo , Perilla/metabolismo , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Ratos , Transdução de SinaisRESUMO
BACKGROUND: To study the correlation of neurological function in degenerative cervical myelopathy (DCM) patients with quantitative assessment of spinal cord compression and impairment by intraoperative ultrasound imaging (IOUSI). METHODS: Twenty-three patients who underwent French-Door laminoplasty for multilevel DCM were followed for 6 months. Modified Japanese Orthopaedic Association (mJOA) score and cervical MRI were assessed before surgery and at postoperative 6 months. IOUS, used to guide decompression, were recorded. The anteroposterior diameter (APD) and the gray values of the IOUSI hyperechogenicity of the midsagittal IOUSI at the narrowest level and at the lesion-free level, and the APD and traverse diameter at the traverse maximum compression level of IOUSI were measured. Maximum spinal cord compression (MSCC), compression rate (CR), and IOUSI gray value ratio (Rgray) were calculated. The appearance of preoperative T2W MRI increased signal intensity (ISI), and the signal change rate (SCR) on postoperative T2W MRI of 9 patients were also measured and calculated, and compared with that of IOUSI hyperechogenicity. RESULTS: Average mJOA score increased significantly from 11.57 ± 2.67 before surgery to 15.39 ± 1.50 at 6 months after surgery, with an average recovery rate (RR) of 71.11 ± 22.81%. The difference between the appearance of preoperative T2W MRI ISI and IOUSI hyperechogenicity was not significant. Spearman correlation analysis found that the IOUSI Rgray were negatively correlated with the RR of mJOA score with a coefficient of - 0.77, and the IOUSI Rgray was not correlated with the postoperative MRI SCR. CONCLUSIONS: In DCM patients, the gray values of IOUSI can be measured accurately. The IOUSI Rgray correlated with postoperative neurological recovery significantly.
Assuntos
Vértebras Cervicais/cirurgia , Laminoplastia/métodos , Doenças da Medula Espinal/diagnóstico , Doenças da Medula Espinal/cirurgia , Ultrassonografia , Idoso , Vértebras Cervicais/diagnóstico por imagem , Descompressão Cirúrgica/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças da Medula Espinal/patologia , Cirurgia Assistida por Computador , Resultado do TratamentoRESUMO
AIM: To determine if CXCL12 (rs1801157) and CXCR4 (rs2228014) polymorphisms are associated with hepatocellular carcinoma (HCC) susceptibility, and detect their expressions in peripheral blood. METHODS: 206 HCC patients, 252 chronic hepatitis B patients, 221 liver cirrhosis patients and 275 healthy volunteers were recruited. Genes CXCL12 and CXCR4 were amplified and genotyped. Their expression in peripheral blood were detected. RESULTS: CXCL12 rs1801157 and CXCR4 rs2228014 polymorphisms were associated with increased susceptibility of HCC, and genotypes GA/AA and CT/TT may be risk factors of HCC (all p < 0.05). Expressions of CXCL12 and CXCR4 in peripheral blood from HCC patients increased significantly (p < 0.05). CONCLUSION: CXCL12 and CXCR4 polymorphisms may be risk factors for HCC, and they may be potential HCC markers.
Assuntos
Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Quimiocina CXCL12/genética , Neoplasias Hepáticas/genética , Receptores CXCR4/genética , Adulto , Alelos , Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Quimiocina CXCL12/sangue , China/epidemiologia , Feminino , Predisposição Genética para Doença , Genótipo , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/sangue , Hepatite B Crônica/genética , Hepatite B Crônica/virologia , Humanos , Incidência , Cirrose Hepática/sangue , Cirrose Hepática/genética , Cirrose Hepática/virologia , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Receptores CXCR4/sangue , Análise de Sequência de DNARESUMO
The present study is aimed to explore the effects of endogenous carbon monoxide on the ischemia-reperfusion in rats. Wistar rats were intraperitoneally injected with protoporphyrin cobalt chloride (CoPP, an endogenous carbon monoxide agonist, 5 mg/kg), zinc protoporphyrin (ZnPP, an endogenous carbon monoxide inhibitor, 5 mg/kg) or saline. Twenty-four hours after injection, the myocardial ischemia-reperfusion model was made by Langendorff isolated cardiac perfusion system, and cardiac function parameters were collected. Myocardial cGMP content was measured by ELISA, and the endogenous carbon monoxide in plasma and myocardial enzymes in perfusate at 10 min after reperfusion were measured by colorimetry. The results showed that before ischemia the cardiac functions of CoPP, ZnPP and control groups were stable, and there were no significant differences. After reperfusion, cardiac functions had significant differences among the three groups (P < 0.05). Compared with pre-ischemia, the cardiac function decreased and obvious cardiac arrest was shown in control and ZnPP groups, while the cardiac function in CoPP group did not change significantly, maintaining a relatively stable level. At the same time, three groups' carbon monoxide level, myocardial enzymology and the cardiac function recovery time after reperfusion also had significant differences (P < 0.05). Compared with those in control group, recovery after reperfusion was faster, activities of creatine kinase and lactic dehydrogenase were significantly decreased, plasma CO and myocardial cGMP contents were significantly increased in CoPP group, while these changes were completely opposite in ZnPP group. It is concluded that endogenous carbon monoxide can maintain cardiac function, shorten the time of cardiac function recovery, and play a protective role in cardiac ischemia-reperfusion.
Assuntos
Monóxido de Carbono/sangue , Traumatismo por Reperfusão Miocárdica , Animais , Monóxido de Carbono/agonistas , Monóxido de Carbono/antagonistas & inibidores , Creatina Quinase/metabolismo , GMP Cíclico/metabolismo , Coração , L-Lactato Desidrogenase/metabolismo , Miocárdio/enzimologia , Protoporfirinas/administração & dosagem , Ratos , Ratos Sprague-Dawley , Ratos WistarRESUMO
BACKGROUND/AIMS: An increase in intracellular lipid droplet formation and hepatic triglyceride (TG) content usually results in nonalcoholic fatty liver disease. However, the mechanisms underlying the regulation of hepatic TG homeostasis remain unclear. METHODS: Oil red O staining and TG measurement were performed to determine the lipid content. miRNA expression was evaluated by quantitative PCR. A luciferase assay was performed to validate the regulation of Yin Yang 1 (YY1) by microRNA (miR)-122. The effects of miR-122 expression on YY1 and its mechanisms involving the farnesoid X receptor and small heterodimer partner (FXR-SHP) pathway were evaluated by quantitative PCR and Western blot analyses. RESULTS: miR-122 was downregulated in free fatty acid (FFA)-induced steatotic hepatocytes, and streptozotocin and high-fat diet (STZ-HFD) induced nonalcoholic steatohepatitis (NASH) in mice. Transfection of hepatocytes with miR-122 mimics before FFA induction inhibited lipid droplet formation and TG accumulation in vitro. These results were verified by overexpressing miR-122 in the livers of STZ-HFD-induced NASH mice. The 3'-untranslated region (3'UTR) of YY1 mRNA is predicted to contain an evolutionarily conserved miR-122 binding site. In silico searches, a luciferase reporter assay and quantitative PCR analysis confirmed that miR-122 directly bound to the YY1 3'UTR to negatively regulate YY1 mRNA in HepG2 and Huh7 cells. The (FXR-SHP) signaling axis, which is downstream of YY1, may play a key role in the mechanism of miR-122-regulated lipid homeostasis. YY1-FXR-SHP signaling, which is negatively regulated by FFA, was enhanced by miR-122 overexpression. This finding was also confirmed by overexpression of miR-122 in the livers of NASH mice. CONCLUSIONS: The present results indicate that miR-122 plays an important role in lipid (particularly TG) accumulation in the liver by reducing YY1 mRNA stability to upregulate FXR-SHP signaling.
Assuntos
Gotículas Lipídicas/metabolismo , MicroRNAs/metabolismo , Triglicerídeos/metabolismo , Fator de Transcrição YY1/metabolismo , Regiões 3' não Traduzidas , Animais , Antagomirs/metabolismo , Sequência de Bases , Linhagem Celular Tumoral , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Dieta Hiperlipídica , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Ácidos Graxos não Esterificados/farmacologia , Proteína do X Frágil da Deficiência Intelectual/genética , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Células Hep G2 , Humanos , Gotículas Lipídicas/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/patologia , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Alinhamento de Sequência , Fator de Transcrição YY1/química , Fator de Transcrição YY1/genéticaRESUMO
BACKGROUND: Stricture formation at the bilioenteric anastomosis is a rare but important postoperative complication. However, information on this complication is lacking in the literature. In the present study, we aimed to assess its prevalence and predictive factors, and report our experience in managing bilioenteric anastomotic strictures over a ten-year period. METHODS: A total of 420 patients who had undergone bilioenteric anastomosis due to benign or malignant tumors between February 2001 and December 2011 were retrospectively reviewed. Univariate and multivariate modalities were used to identify predictive factors for anastomotic stricture occurrence. Furthermore, the treatment of anastomotic stricture was analyzed. RESULTS: Twenty-one patients (5.0%) were diagnosed with bilioenteric anastomotic stricture. There were 12 males and 9 females with a mean age of 61.6 years. The median time after operation to anastomotic stricture was 13.6 months (range, 1 month to 5 years). Multivariate analysis identified that surgeon volume (≤30 cases) (odds ratio: -1.860; P=0.044) was associated with the anastomotic stricture while bile duct size (>6 mm) (odds ratio: 2.871; P=0.0002) had a negative association. Balloon dilation was performed in 18 patients, biliary stenting in 6 patients, and reoperation in 4 patients. Five patients died of tumor recurrence, and one of heart disease. CONCLUSIONS: Bilioenteric anastomotic stricture is an uncommon complication that can be treated primarily by interventional procedures. Bilioenteric anastomosis may be performed by a surgeon in his earlier training period under the guidance of an experienced surgeon. Bile duct size >6 mm may play a protective role.
Assuntos
Procedimentos Cirúrgicos do Sistema Biliar/efeitos adversos , Colestase/epidemiologia , Colestase/terapia , Neoplasias do Sistema Digestório/cirurgia , Idoso , Anastomose Cirúrgica , Procedimentos Cirúrgicos do Sistema Biliar/mortalidade , Distribuição de Qui-Quadrado , China/epidemiologia , Colecistectomia/efeitos adversos , Coledocostomia/efeitos adversos , Colestase/diagnóstico , Colestase/mortalidade , Constrição Patológica , Neoplasias do Sistema Digestório/mortalidade , Neoplasias do Sistema Digestório/patologia , Dilatação , Feminino , Humanos , Jejunostomia/efeitos adversos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prevalência , Reoperação , Estudos Retrospectivos , Fatores de Risco , Stents , Fatores de Tempo , Resultado do TratamentoRESUMO
To elucidate proteomic changes of Hpt cells from red claw crayfish, Cherax quadricarinatus, we have carried out isobaric tags for relative and absolute quantitation (iTRAQ) of cellular proteins at both early (1 hpi) and late stage (12 hpi) post white spot syndrome virus (WSSV) infection. Protein database search revealed 594 protein hits by Mascot, in which 17 and 30 proteins were present as differentially expressed proteins at early and late viral infection, respectively. Generally, these differentially expressed proteins include: 1) the metabolic process related proteins in glycolysis and glucogenesis, DNA replication, nucleotide/amino acid/fatty acid metabolism and protein biosynthesis; 2) the signal transduction related proteins like small GTPases, G-protein-alpha stimulatory subunit, proteins bearing PDZ- or 14-3-3-domains that help holding together and organize signaling complexes, casein kinase I and proteins of the MAP-kinase signal transduction pathway; 3) the immune defense related proteins such as α-2 macroglobulin, transglutaminase and trans-activation response RNA-binding protein 1. Taken together, these protein information shed new light on the host cellular response against WSSV infection in a crustacean cell culture.
Assuntos
Proteínas de Artrópodes/genética , Astacoidea/imunologia , Vírus da Síndrome da Mancha Branca 1/fisiologia , Animais , Proteínas de Artrópodes/metabolismo , Astacoidea/genética , Astacoidea/virologia , Sistema Hematopoético/imunologia , Proteômica/métodos , Análise de Sequência de DNAAssuntos
Hepatectomia/métodos , Veia Ilíaca/transplante , Leiomiossarcoma/cirurgia , Neoplasias Vasculares/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Veia Cava Inferior/cirurgia , Adulto , Feminino , Humanos , Imageamento Tridimensional , Leiomiossarcoma/diagnóstico , Fígado/irrigação sanguínea , Tomografia Computadorizada por Raios X , Transplante Homólogo , Neoplasias Vasculares/diagnóstico , Veia Cava Inferior/diagnóstico por imagemRESUMO
BACKGROUND: At the time of diagnosis, most patients with gallbladder cancer are in advanced stage and the cancer is unresectable. Long-term survivors are usually seen in a small number of patients with incidental gallbladder cancer. This study aimed to identify preoperative predictors of incidental gallbladder cancer in elderly patients. METHODS: A total of 4014 patients of more than 44 years old who had undergone cholecystectomy at our department from January 2000 to December 2010 were retrospectively reviewed. Univariate and multivariate modalities were used to identify the predictive factors of incidental gallbladder cancer. RESULTS: Twenty-nine of the 4014 patients who had undergone cholecystectomy for benign gallbladder diseases were histologically diagnosed as having incidental gallbladder cancer. Multivariate analysis identified that elevated carbohydrate antigen 19-9 combined with carcinoembryonic antigen and/or carbohydrate antigen 125 (P=0.045), a gallbladder polyp greater than or equal to 1.2 cm (P=0.043) and focal gallbladder wall thickening of more than or equal to 5 mm (P=0.002) were predictive factors of incidental gallbladder cancer. CONCLUSION: Cholecystectomy is suggested for patients with these predictive factors and intraoperative frozen section should be considered to rule out carcinoma.
Assuntos
Neoplasias da Vesícula Biliar/diagnóstico , Achados Incidentais , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Antígeno Ca-125/sangue , Antígeno CA-19-9/sangue , Antígeno Carcinoembrionário/sangue , China , Colecistectomia , Feminino , Neoplasias da Vesícula Biliar/sangue , Neoplasias da Vesícula Biliar/patologia , Humanos , Masculino , Proteínas de Membrana/sangue , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Estudos Retrospectivos , Fatores de Risco , Regulação para CimaAssuntos
Síndrome de Budd-Chiari/diagnóstico por imagem , Síndrome de Budd-Chiari/cirurgia , Doença Hepática Terminal/cirurgia , Veias Hepáticas , Veia Cava Inferior , Adulto , Síndrome de Budd-Chiari/complicações , Circulação Colateral , Doença Hepática Terminal/etiologia , Veias Hepáticas/diagnóstico por imagem , Humanos , Transplante de Fígado , Imageamento por Ressonância Magnética , Masculino , Veia Cava Inferior/diagnóstico por imagemRESUMO
OBJECTIVE: To investigate the effect of pulsed electromagnetic tields (FEMFs) on osteogemc differentiation and Wnt/ß-catenin signaling pathway in rat bone marrow mesenchymal stem cells (BMSCs). METHODS: Rat BMSCs were isolated and the passage 3 cells were divided into 3 groups. Cells were cultured in LG-DMEM complete medium for 1 d to ensure fully adherent. Then, change the medium. Cells were maintained in complete medium (Control group) or in osteo-induction medium (OM group). The cells in PEMFs group were cultured in complete medium and exposed to 8 Hz, 3. 8 mT PEMF stimulation for 40 min/d. The intervention lasted for 21 d. Cell proliferation activity was determined by using MTT. The effects of PEMF onosteogenic differentiation were assessed by ALP and Alizarin Red S staining. Various osteoblast-relevant genes and genes of Wnt/ß-catenin signaling were analyzed by quantitative real-time RT-PCR. RESULTS: We. found that OM could significantly promote the proliferation of BMSC at 7 d, 14 d, 21 d (P<0. 05), but the effect was not obviously found in PEMFs group. For osteogenic differentiation, the positive rates of ALP or Alizarin Red S staining were detected higher in PEMFs/ OM group (P < 0. 05). Quantitative RT-PCR revealed PEMFs or OM could increase mRNA levels of Wnt1, Wnt3a, LRP5, ß-catenin, BMP-2, Runx2, ALP, OC at special time point (P<0. 05). Compared to OM group, PEMFs have a lower expression in each detection, but the trends were consistent. CONCLUSION: PEMFs (8 Hz, 3. 8 mT) could induce the osteogenic differentiation of rat BMSCs via activating Wnt/ß-catenin signaling pathway.