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Acute myocardial infarction (AMI) is one of the most serious cardiovascular diseases worldwide. Advances in genomics have provided new ideas for the development of novel molecular biomarkers of potential clinical value for AMI. Methods: Based on microarray data from a public database, differential analysis and functional enrichment analysis were performed to identify aberrantly expressed genes in AMI and their potential functions. CIBERSORT was used for immune landscape analysis. We also obtained whole blood samples of 3 patients with AMI and performed second-generation sequencing (SGS) analysis. Weighted gene co-expression network analysis (WGCNA) and cross-tabulation analysis identified AMI-related key genes. Receiver operating characteristic (ROC) curves were used to assess the diagnostic power of key genes. Single-gene gene set enrichment analysis (GSEA) revealed the molecular mechanisms of diagnostic indicators. Results: A total of 53 AMI-related DEGs from a public database were obtained and found to be involved in immune cell activation, immune response regulation, and cardiac developmental processes. CIBERSORT confirmed that the immune microenvironment was altered between AMI and normal samples. A total of 77 hub genes were identified by WGCNA, and 754 DEGs were obtained from own SGS data. Seven diagnostic indicators of AMI were obtained, namely GZMA, NKG7, TBX21, TGFBR3, SMAD7, KLRC4, and KLRD1. The single-gene GSEA suggested that the diagnostic indicators seemed to be closely implicated in cell cycle, immune response, cardiac developmental, and functional regulatory processes. Conclusion: The present study provides new diagnostic indicators for AMI and further confirms the feasibility of the results of genome-wide gene expression analysis.
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A number of previous studies have demonstrated that inhibiting autophagy can increase the cellular cytotoxicity of chemotherapeutic agents in urothelial cancer cells. However, the mechanistic roles of autophagy in gemcitabine (GEM) resistant bladder cancer cells have not been thoroughly investigated. In the present study, immunohistochemistry staining of autophagy marker LC3 was performed in bladder cancer and healthy control tissues and demonstrated an essential role of autophagy in cancer development. A GEM-resistant cell line was established to assess the effects of autophagy on the acquisition of GEM resistance. Western blotting of autophagy markers in GEM-resistant bladder cancer cells suggested that GEM resistance was caused, at least partially, by GEM-induced autophagy. GEM resistance was demonstrated to be reversed by the inhibition of autophagy by 3-methyladenine. In addition, oblongifolin C (OC), a novel autophagic flux inhibitor purified from traditional Chinese medicine, was found to enhance the efficiency of GEM in GEM-resistant bladder cancer cells by inhibiting autophagic flux. In conclusion, data from the present study suggest that autophagy serves an important role in bladder cancer development and GEM resistance. OC treatment has the ability to reverse GEM-resistance in bladder cancer cells by suppressing autophagic flux, thereby providing a potential adjunctive therapeutic option for bladder cancer GEM treatment.
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Earthworms may regulate carbon (C) mineralization through a top-down process by altering microbiota community and/or a bottom-up process by providing basic conditions such as mineralizable substrates. However, these two roles performed by earthworms have not been separately quantified. Here, we focused on how the pantropical widespread earthworm, Pontoscolex corethrurus, affected CO2 emission by changing soil microbiota community and substrate availability in infertile subtropical soils. Two experiments were performed. Firstly, we conducted a 3-year field experiment wherein P. corethrurus population was manipulated by electrical shocking. The two treatments were earthworm reduction (ER) and earthworm addition (EA). Thereby, we tried to understand CO2 emission pattern through the earthworm-induced changes in soil microbiota community and C-related enzyme activities in field plots. Secondly, a cross-soil inoculation microcosm experiment was conducted to partition the contributions of earthworm-regulated microbiota community and substrate quality to CO2 emission. The four treatments were 1) autoclaved ER soil + ER microbiota, 2) autoclaved EA soil + ER microbiota, 3) autoclaved ER soil + EA microbiota, and 4) autoclaved EA soil + EA microbiota. We found that, in the field experiment, earthworm addition changed soil microbiota community structure, but increased CO2 emission despite decreasing soil ß-glucosidase activity by 12%. In the cross-inoculation experiment, the ß-glucosidase activity and CO2 emission (1-day incubation) in EA soils was 65.5% and 35.5% greater than that in the ER soils, respectively; the cumulative CO2 emission (30-day incubation) in EA soils was also significantly greater than that in ER soils. However, no significant effects of microbiota inoculation on soil CO2 emissions were observed. These results suggested that the earthworm-enhanced substrate availability, rather than the earthworm-induced changing in the microbiota community structure and enzymatic activities, played a key role in C mineralization. This study implies that P. corethrurus occupies a "bottom niche" in infertile subtropical soils.
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Microbiota , Oligoquetos , Animales , Carbono , Dióxido de Carbono , SueloRESUMEN
The central objective was to identify the role of the PI3K-Akt activation pathway on the neuroprotection of δ-opioid receptor agonist (DADLE) against cerebral ischemia-reperfusion (I/R) injury in a rat model. Fifty-five male Sprague-Dawley (SD) rats were included to establish a middle cerebral artery occlusion (MCAO) model which were then divided into the sham, MCAO, LY294002 (MCAO+DADLE+LY294002 [inhibitor of PI3K-Akt pathway]), DADLE (MCAO+DADLE) and DMSO (MCAO+DADLE+DMSO [dimethyl sulphoxide]) groups. The cerebral infarction (CI) volume and nerve cell apoptosis was determined using TTC and TUNEL staining. Quantitative real-time polymerase chain reaction (qRT-PCR), western blotting and immunohistochemistry staining were applied for the expressions of Bad, Bax, Bcl-2 and cleaved caspase-3. The MCAO group showed higher CI volume, nerve cell apoptosis and cleaved caspase-3 expressions than the DADLE and DMSO groups, which were also higher in the LY294002 group than the DADLE group. Compared with the MCAO group, the mRNA and protein expressions of PI3K and Bcl-2, and the protein expressions of p-Akt and p-Bad were elevated, while the mRNA and protein expressions of Bax were decreased in the DADLE and DMSO groups. Decreased mRNA and protein expressions of PI3K and Bcl-2, reduced protein expressions of p-Akt and p-Bad and elevated mRNA and protein expressions of Bax exhibited in the LY294002 group than the DADLE group. These results indicate that activation of PI3K-Akt pathway promotes the neuroprotection of DADLE against cerebral I/R injury in a rat model by decreasing nerve cells apoptosis.
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Isquemia Encefálica/tratamiento farmacológico , Neuroprotección/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores Opioides delta/agonistas , Daño por Reperfusión/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Isquemia Encefálica/metabolismo , Caspasa 3/metabolismo , Ciclina D1/metabolismo , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/metabolismo , Masculino , ARN Mensajero/metabolismo , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo , Transducción de Señal/efectos de los fármacos , Proteína X Asociada a bcl-2/metabolismoRESUMEN
Although some studies have reported potential associations of dietary patterns with depression risk, a consistent perspective hasn't been estimated to date. Therefore, we conducted this meta-analysis to evaluate the relation between dietary patterns and the risk of depression. A literature research was conducted searching MEDLINE and EMBASE databases up to September 2016. In total, 21 studies from ten countries met the inclusion criteria and were included in the present meta-analysis. A dietary pattern characterized by a high intakes of fruit, vegetables, whole grain, fish, olive oil, low-fat dairy and antioxidants and low intakes of animal foods was apparently associated with a decreased risk of depression. A dietary pattern characterized by a high consumption of red and/or processed meat, refined grains, sweets, high-fat dairy products, butter, potatoes and high-fat gravy, and low intakes of fruits and vegetables is associated with an increased risk of depression. The results of this meta-analysis suggest that healthy pattern may decrease the risk of depression, whereas western-style may increase the risk of depression. However, more randomized controlled trails and cohort studies are urgently required to confirm this findings.
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Depresión/etiología , Dieta/psicología , Ingestión de Alimentos/psicología , Conducta Alimentaria/psicología , Animales , Dieta/métodos , Femenino , Alimentos , Humanos , Masculino , Factores de RiesgoRESUMEN
The study aims at investigating the effects of coagulation factors VIII/XI/XIII polymorphisms in coagulation factor activities and deep vein thrombosis (DVT). A total of 130 patients with history of artificial joint replacement surgery were recruited, including 65 patients with DVT (cases) and 65 patients without DVT (controls). Cases and controls had comparable age, sex, and body mass index. Activities of VIII/XI and XIII were, respectively, detected by 1 phase anticoagulation method and microtitrimetry. Polymorphisms of VIII rs1800291 (3591C>G), XI rs2289252 (25264C>T), and XIII rs5985 (103G>T) were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Activities of VIII/XI were significantly increased in cases than in controls (P < 0.001 for VIII, P = 0.024 for XI). Activity of XI was significantly increased by 11.11% in CT + TT mutant type (25264C>T) compared with wild-type CC (95% confidence interval (CI), 2.28-19.95). In univariate analysis, incidence of DVT for CT mutant was 2.41-fold compared with wild-type CC (95% CI, 1.16-5.03). T allele had 1.83-fold increased risk of DVT than C allele (95% CI, 1.06-3.14). In multivariate analysis, incidence of DVT for CT + TT mutant type was 2.39-fold compared with wild type (95% CI, 1.07-5.35). Distributions of VIII gene 3951C>G and genotypes were not significant between groups (both P > 0.05). The mutation rate of VIII gene 103G>T was low in study population (0.77%) and was not significant between groups. XI 25264C>T genotype is significantly associated with XI activity. T mutation of this locus significantly increases XI activity and is a risk factor for DVT.