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1.
World J Pediatr ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32026148

RESUMO

Since December 2019, an epidemic caused by novel coronavirus (2019-nCoV) infection has occurred unexpectedly in China. As of 8 pm, 31 January 2020, more than 20 pediatric cases have been reported in China. Of these cases, ten patients were identified in Zhejiang Province, with an age of onset ranging from 112 days to 17 years. Following the latest National recommendations for diagnosis and treatment of pneumonia caused by 2019-nCoV (the 4th edition) and current status of clinical practice in Zhejiang Province, recommendations for the diagnosis and treatment of respiratory infection caused by 2019-nCoV for children were drafted by the National Clinical Research Center for Child Health, the National Children's Regional Medical Center, Children's Hospital, Zhejiang University School of Medicine to further standardize the protocol for diagnosis and treatment of respiratory infection in children caused by 2019-nCoV.

2.
Drug Des Devel Ther ; 14: 13-25, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32021088

RESUMO

Purpose: Our previous studies have indicated that non-muscle myosin heavy chain IIA (NMMHC IIA) is involved in H2O2-induced neuronal apoptosis, which is associated with the positive feedback loop of caspase-3/ROCK1/MLC pathway. However, the neuroprotective effect of NMMHC IIA inhibition with an adeno-associated virus (AAV) vector after transient middle cerebral artery occlusion (MCAO) and its role in caspases-3/ROCK1/MLC pathway remain blurred. Methods: Green fluorescent protein (GFP) and a small hairpin RNA targeting Myh9 (encoding NMMHC IIA) were cloned and packaged into the AAV9 vector. AAV-shMyh9 or control vector were injected into C57BL/6J mice four weeks prior to 60 min MCAO. Twenty-four hours after reperfusion, functional and histological analyses of the mice were performed. Results: In this study, AAV-shMyh9 was used to down-regulate NMMHC IIA expression in mice. We found that down-regulation of NMMHC IIA could improve neurological scores and histological injury in ischemic mice. Ischemic attack also activated neuronal apoptosis, and this effect was partially attenuated when NMMHC IIA was inhibited by AAV-shMyh9. In addition, AAV-shMyh9 significantly reduced cerebral ischemic/reperfusion (I/R)-induced NMMHC IIA-actin interaction, caspase-3 cleavage, Rho-associated kinase1 (ROCK1) activation and myosin light-chains (MLC) phosphorylation. Conclusion: Consequently, we showed that AAV-shMyh9 inhibits I/R-induced neuronal apoptosis linked with caspase-3/ROCK1/MLC/NMMHC IIA-actin cascade, which has also been confirmed to be a positive feedback loop. These findings put some insights into the neuroprotective effect of AAV-shMyh9 associated with the regulation of NMMHC IIA-related pathway under ischemic attack and provide a therapeutic strategy for ischemic stroke.

3.
Clin Transplant ; : e13810, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32011059

RESUMO

This retrospective multicentre cohort study aimed to compare the outcome of haploidentical haematopoietic stem cell transplantation (HID-HSCT) with matched sibling donor (MSD) and unrelated donor (URD) transplantation in severe aplastic anaemia (SAA) patients 40 years of age and older. With a median follow-up time of 17.6 months, 85 consecutive patients were enrolled in the study, and the median patient age was 45 years (40,58). All patients achieved myeloid engraftment, and the cumulative engraftment rate of platelets was 92.9±0.1%. The cumulative incidences of Grade 2-4 acute graft versus host disease (aGvHD) and chronic graft versus host disease (cGvHD) at 3 years were 14.1±0.1% and 17.3±0.2%. The 3-year estimated overall survival (OS) and failure-free survival (FFS) were 91.2±3.2% and 89.7±3.5%. In multivariate analysis, the only factor associated with inferior survival was an ECOG-score ≥2. HID-HSCT was associated with a higher incidence of GvHD., but the difference of 3-year estimated OS between HID group and the other two cohorts was not significant (86.7±6.4% for HID vs. 86.7±6.4% for MSD and 86.7±6.4% for URD, p=0.481). HID-HSCT might be a feasible alternative option for selected SAA patients aged 40 years and older without a matched donor.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31932654

RESUMO

The impact of ABO incompatibility on transplantation outcomes in severe aplastic anemia (SAA) patients receiving haploidentical hematopoietic stem cell transplantation (HSCT) remains controversial without published data. A total of 199 SAA patients receiving haploidentical HSCT from ABO-matched (n = 114), minor ABO-incompatible (n = 47), or major ABO-incompatible donors (n = 38) were included in this study. The median time and cumulative incidences of both myeloid and platelet engraftment in the ABO-compatible and ABO-incompatible groups were similar, and pure red cell aplasia was absent. Minor ABO incompatibility increased the rate of grade III-IV acute graft-versus-host disease (aGVHD) (ABO compatible: 6.14 ± 0.05%, minor incompatible: 19.15 ± 0.34%, and major incompatible: 10.53 ± 0.25%; P = 0.051), but did not influence the rates of grade II-IV aGVHD or chronic GVHD (cGVHD). Minor ABO-incompatibility was identified as an independent risk factor for grade III-IV aGVHD by multivariate analysis (hazard ration (HR) = 4.00 (1.48-10.80), P = 0.006). Chronic GVHD, mortality, and treatment failure were not increased in the minor ABO-incompatible group. For SAA patients receiving haploidentical HSCT, ABO compatible donors are better than ABO minor incompatible donors if several haploidentical donors are available.

6.
Luminescence ; 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898376

RESUMO

Dy3+ -doped Y3 Al5 O12 phosphors were prepared at a relatively low temperature using molten salt synthesis. The phase of the prepared Dy3+ -doped Y3 Al5 O12 phosphors was confirmed using X-ray powder diffraction. Results indicated that Dy3+ doping did not change the Y3 Al5 O12 phase. Following excitation at 352 nm, emission spectra of the Dy3+ -doped Y3 Al5 O12 phosphors consisted of blue, yellow, and red emission bands. The influence of Dy3+ concentration and excitation wavelength on emission was investigated. The ratio of yellow light to blue light varied with change in Dy3+ doping concentration, due to changes in the structure around Dy3+ . Emission intensities also changed when the excitation wavelength was changed. This variation is luminescence generated a system for tunable white light for Dy3+ -doped Y3 Al5 O12 phosphors.

7.
Mol Plant ; 13(1): 128-143, 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31698047

RESUMO

Plant plasmodesmata (PDs) are specialized channels that enable communication between neighboring cells. The intercellular permeability of PDs, which affects plant development, defense, and responses to stimuli, must be tightly regulated. However, the lipid compositions of PD membrane and their impact on PD permeability remain elusive. Here, we report that the Arabidopsis sld1 sld2 double mutant, lacking sphingolipid long-chain base 8 desaturases 1 and 2, displayed decreased PD permeability due to a significant increase in callose accumulation. PD-located protein 5 (PDLP5) was significantly enriched in the leaf epidermal cells of sld1 sld2 and showed specific binding affinity to phytosphinganine (t18:0), suggesting that the enrichment of t18:0-based sphingolipids in sld1 sld2 PDs might facilitate the recruitment of PDLP5 proteins to PDs. The sld1 sld2 double mutant seedlings showed enhanced resistance to the fungal-wilt pathogen Verticillium dahlia and the bacterium Pseudomonas syringae pv. tomato DC3000, which could be fully rescued in sld1 sld2 pdlp5 triple mutant. Taken together, these results indicate that phytosphinganine might regulate PD functions and cell-to-cell communication by modifying the level of PDLP5 in PD membranes.

8.
Environ Pollut ; 256: 113369, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31662254

RESUMO

Soil contains large amounts of humic acid (HA), iron ions and manganese ions, all of which affect U(VI) migration in the soil. HA interacts with iron and manganese ions to form HA salts (called HA-Fe and HA-Mn in this paper); however, the effects of HA-Fe and HA-Mn on the migration of U(VI) is not fully understood. In this study, HA-Fe and HA-Mn were compounded by HA interactions with ferric chloride hexahydrate and manganese chloride tetrahydrate, respectively. The influence of HA, HA-Fe and HA-Mn on U(VI) immobilization and migration was investigated by bath adsorption experiments and adsorption-desorption experiments using soil columns. The results showed that the presence of HA, HA-Fe and HA-Mn retarded the migration of U(VI) in soil. Supported by X-ray photoelectron spectroscopy (XPS) and BCR sequential extraction analyses, a plausible explanation for the retardation was that HA-Fe and HA-Mn could reduce hexavalent uranium to stable tetravalent uranium and increase the specific gravity of Fe/Mn oxide-bound uranium and organic/sulfide-bound uranium, which made it difficult for them to longitudinally migrate in soil. Scanning electron microscopy (SEM), Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), and surface area and pore size analyses indicated that the complex formed between the hydroxyl, amino and carboxyl groups of HA-Fe and U(VI) increased the crystallinity of HA-Fe. The reaction between U(VI) and the hydroxyl, amino, aldehyde, keto and chlorine-containing groups of HA-Mn had no effect on the crystallinity of HA-Mn. Notably, the column desorption experiment found that the U(VI) immobilized in the soil remigrated under the effect of rain leaching, and acid rain promoted uranium remigration better than neutral rain. The findings provide some guidance for the decommissioning disposal of uranium contaminated site and it's risk assessments.

9.
J Sci Food Agric ; 100(1): 315-324, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31525262

RESUMO

BACKGROUND: In order to utilize tilapia skin gelatin hydrolysate protein, which is normally discarded as industrial waste in the process of fish manufacture, we study the in vivo and in vitro angiotensin-I-converting enzyme (ACE) inhibitory activity of the peptide Leu-Ser-Gly-Tyr-Gly-Pro (LSGYGP). The aim was to provide a pharmacological basis of the development of minimal side effects of ACE inhibitors by comparative analysis with captopril in molecular docking. RESULTS: This peptide from protein-rich wastes showed excellent ACE inhibitory activity (IC50  = 2.577 µmol L-1 ) and exhibited a mixed noncompetitive inhibitory pattern with Lineweaver-Burk plots. Furthermore, LSGYGP and captopril groups both showed significant decreases in blood pressure after 6 h and maintained good digestive stability over 4 h. Molecular bond interactions differentiate competitive captopril upon hydrogen bond interactions and Zn(II) interaction. The C-terminal Pro generates three interactions (hydrogen bonds, hydrophilic interactions and Van der Waals interactions) in the peptide and effectively interacts with the S1 and S2 pockets of ACE. CONCLUSION: LSGYGP, with an IC50 value of 2.577 µmol L-1 , has an antihypertensive effect in spontaneously hypertensive rats. Through comparison with captopril, this study revealed that LSGYGP may be a potential food-derived ACE inhibitory peptide and could act as a functional food ingredient to prevent hypertension. © 2019 Society of Chemical Industry.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/química , Anti-Hipertensivos/química , Captopril/química , Hipertensão/tratamento farmacológico , Peptídeos/química , Sequência de Aminoácidos , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Inibidores da Enzima Conversora de Angiotensina/metabolismo , Animais , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Captopril/administração & dosagem , Ciclídeos , Digestão , Proteínas de Peixes/química , Trato Gastrointestinal/metabolismo , Humanos , Ligações de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Cinética , Masculino , Simulação de Acoplamento Molecular , Peptídeos/metabolismo , Peptídeos/farmacologia , Peptidil Dipeptidase A/química , Peptidil Dipeptidase A/metabolismo , Hidrolisados de Proteína/química , Hidrolisados de Proteína/metabolismo , Ratos , Ratos Endogâmicos SHR
10.
J Agric Food Chem ; 68(1): 213-224, 2020 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-31861958

RESUMO

Asparanin A (AA), a steroidal saponin from Asparagus officinalis L., has anticancer activity: however, its detailed molecular mechanisms in endometrial cancer (EC) have not been studied so far. We evaluated the anticancer activity and underlying mechanism of AA on EC cell line Ishikawa in vitro and in vivo. AA inhibited the Ishikawa cell proliferation and caused cell morphology alteration and cell cycle arrest in G0/G1 phase. Moreover, it could induce apoptosis through mitochondrial pathway, including the deregulation of Bak/Bcl-xl ratio which led to the generation of ROS, up-regulation of cytochrome c followed by decrease of Δψm, and activation of caspases, besides inhibition of the PI3K/AKT/mTOR pathway. In vivo data showed that administration of AA significantly inhibited the tumor tissue cell proliferation, reduced the tumor growth, and induced the apoptosis occurrence. AA can be a possible functional food ingredient to cure endometrial cancer followed by clinical trials.


Assuntos
Antineoplásicos Fitogênicos/administração & dosagem , Asparagus (Planta)/química , Neoplasias do Endométrio/tratamento farmacológico , Pontos de Checagem da Fase G1 do Ciclo Celular/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Extratos Vegetais/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismo , Saponinas/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Citocromos c/metabolismo , Neoplasias do Endométrio/fisiopatologia , Feminino , Humanos , Camundongos Endogâmicos BALB C , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/genética , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Fase de Repouso do Ciclo Celular/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
11.
Cancer Cell Int ; 19: 293, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31807115

RESUMO

Background: Although leukemic blast cells of Pro-B cell acute lymphoblastic leukemia (ALL) are arrested at the same stage of B cell differentiation, the immature B cell subtype is still biologically heterogeneous and is associated with diverse outcomes. This study aimed to explore the clinical-biological characteristics of pediatric pro-B ALL and factors associated with outcomes. Methods: This study enrolled 121 pediatric patients aged 6 months to 14 years with newly diagnosed CD19+CD10- pro-B cell acute lymphoblastic leukemia (pro-B ALL) treated at Beijing Children's Hospital from March 2003 to October 2018. Genetic abnormalities, immunophenotypic markers, minimal residual disease (MRD) at early treatment stage and long-term outcomes of children treated on two consecutive protocols were analyzed. Results: KMT2A rearrangements were the most frequent abnormalities (incidence rate 33.06%), and were associated with lower frequency of CD13, CD33, CD22 and CD34 expression and higher frequency of CD7 and NG2 expression. Higher frequency of CD15 and CD133 expression was found in KMT2A-AFF1 + patients, exclusively. Presence of CD15 and absence of CD34 at diagnosis correlated with the high burden of MRD at the early stage of treatment. Outcomes were more favorable in patients older than 1 year, with absence of CD20 expression and KMT2A rearrangements, and with MRD lower than 1% at the end of induction and 0.1% before consolidation. Increased intensity of chemotherapy based on MRD analysis did not improve outcomes significantly (5-year EFS 73.9 ± 6.5% for BCH-2003 and 76.1 ± 5.3% for CCLG-2008, P = 0.975). Independent adverse prognostic factors were MRD ≥ 0.1% before consolidation and presence of KMT2A gene rearrangements (odds ratios [ORs] 9.424 [95% confidence interval (CI) 3.210, 27.662; P < 0.001]; 4.142 [1.535, 11.715, P = 0.005]; respectively). Conclusions: Pediatric pro-B ALL is a heterogeneous disease. Genetic analysis and MRD evaluation can predict patients with dismal prognosis; however, intensive chemotherapy alone does not improve outcomes of these patients and targeted therapy or hematopoietic stem cell transplantation may be required.

12.
Huan Jing Ke Xue ; 40(9): 3973-3981, 2019 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-31854859

RESUMO

Nitrous acid (HONO) is easily photolyzed with the production of·OH, which plays an important role in the formation of regional secondary pollution. In China, research of HONO observation is concentrated mainly in urban areas and is rarely reported in rural areas. In our study, a one-month HONO field observation was conducted at the Station of Rural Environment, Chinese Academy of Sciences (Dongbaituo Village, Wangdu County, Hebei Province) in November 2017 using the long path absorption photo meter (LOPAP). The concentration, variety characteristics, and budget of HONO was studied. During the observation period, HONO exhibited pronounced diurnal variation with low concentrations in the day and high concentration in the evening. The highest concentration at night was about 3.70×10-9, and the lowest concentration at noon was about 0.10×10-9, indicating the presence of a strong source of HONO in rural areas. The CO concentration increased significantly before and after heating, whereas the HONO concentration did not change significantly, indicating that heating combustion contributed less to HONO, Direct emission of motor vehicles at night contributed 23.20% and 31.20% to HONO in polluted and clean weather conditions, respectively, indicating the presence of strong sources of HONO in polluted weather conditions. The average formation rate of HONO at night from homogeneous reaction of·OH and NO could reach 0.40×10-9 h-1, which is 0.67 times higher than that of heterogeneous reaction of NO2 (0.24×10-9 h-1), indicating that the homogeneous reaction of·OH and NO is the main source of HONO at night. HONO has a strong unknown source in the daytime with an intensity reaching 1.37×10-9 h-1, which contributes about 50% to HONO.

13.
J Crohns Colitis ; 2019 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-31841595

RESUMO

BACKGROUND AND AIMS: Despite the therapeutic promise of stem cell therapy in the treatment of inflammatory bowel diseases (IBD), the most donor cell populations have to be obtained via invasive approaches and often remain insufficiently validated. Urine-derived stem cells (USC) were recently shown to have regenerative properties, which can be harvested in a safe, low-cost and non-invasive way. This study aims to evaluate the immunomodulatory effect of USC and its efficacy in the management of IBD. METHODS: Human USC were isolated and expanded from the urine of healthy male adult volunteers (n=3, age arrange 24-30 years old). USC were characterized by cell surface marker expression profile and multipotent differentiation. In vitro immunomodulatory effect of USC was evaluated by co-culturing with human CD4+ T cells upon stimulation with Phytohaemagglutinin (PHA). The proliferation of CD4+ T was measured by FACS. Cytokine array and quantitative RT-PCR were applied to examine cytokine levels. In vivo therapeutic value of USC was assessed using murine colitis model induced by dextran sulfate sodium (DSS) or 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). The immunomodulatory effect of USC and bone marrow-derived mesenchymal stem cells (BMSC) was compared when co-cultured with CD4+ T cells. The therapeutic efficacy of USC and BMSC on IBD was compared when administrated in acute DSS model in vivo. RESULTS: USC were positive for mesenchymal stem cell markers but were negative for hematopoietic stem cell markers. These cells differentiated into osteo-, adipo- and chondro-genic cell lineages. Similar to BMSC, the proliferation of CD4+ T cells was significantly inhibited when co-cultured with USC, as a consequence of Th1/Th17 immune response inhibition. Systemic administration of USC significantly ameliorated the clinical and histopathological severity of colitis and increased the survival rate in both acute and chronic murine colitis models. Moreover, implantation of USC led down-regulation of the Th1/Th17 immune responses in a PGE2-dependent manner. CONCLUSIONS: This study demonstrated that implantation of USC reduces inflammation in IBD rodent model via downregulation of Th1/Th17 immune responses, indicating that USC therapy serves as a potential cell-based therapeutic candidate for IBD.

14.
Acta Trop ; 203: 105301, 2019 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-31843385

RESUMO

Toxoplasma gondii (T. gondii) is a common parasite worldwide, which can cause encephalitis, enteritis and miscarriage in abortion women. This study examined the cecal microbiome of mice infected with T. gondii through analysis of 16S rRNA genes determined by Illumina sequencing. BALB/c mice were orally infected with sporulated T. gondii oocysts. Mice were killed after 13-days- and 21-days- post infection, respectively, then their cecal contents were extracted and examined to determine the composition of gut microflora by illumina sequencing of the V3 +V4 region of the 16S rRNA genes. Our results showed the alterations in the gut microbes of BALB/c mice infected with T. gondii infection, where we observed a significant shift in the relative abundance of cecal bacteria. In mice at 13 days post-infection, the relative abundance of Proteobacteria increased, along with that of harmful bacteria, such as Bilopha and Desulfovibrio. However, the abundance of Lactobacillus decreased. At 21 days post-infection, the abundance of Lactobacillus was more than that observed for the uninfected control, with harmful bacteria, such as Bilopha and Desulfovibrio being reduced. The mice at 21-days post-infection had more beneficial intestinal bacteria than the control group. Our results suggested that the gut microbiota play an important role in disease progression from acute infection to chronic infection.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31874219

RESUMO

Acute pancreatitis (AP) has been recognized as an uncommon yet potentially lethal complication after hematopoietic stem cell transplant (HSCT). This retrospective, nested, case-control study reviewed data from 5284 consecutive patients who underwent allogeneic (allo)-HSCT between 2009 and 2018 at a single center, identifying 40 patients (0.76%) with AP after allo-HSCT. The diagnosis and severity of AP were established and classified according to existing criteria. Younger age (P = .008), grades II to IV acute graft-versus-host disease (P = .010), a history of donor lymphocyte infusion (P = .033), and pre-existing gallstones (P = .003) were independent risk factors of AP after allo-HSCT. Post-transplant AP had a trend to negatively influence overall survival (OS) and nonrelapse mortality (NRM) (P = .063) for allo-HSCT recipients, but no significant difference was found. Patients with moderately severe and severe AP had significantly lower OS (P = .002) and higher NRM (P = .000) than other patients. Based on these findings, a risk score model was also established to predict the occurrence of AP. Our risk score model performed well in terms of discrimination when applied to derivation samples. Patients were classified into a low-risk group (0 to 1 point), a medium-risk group (2 to 3 points), and a high-risk group (4 points or more). Significant difference was observed in AP incidence among the 3 groups. The predictive tool explored by our study might contribute to target high-risk patients and guide personalized AP prevention in allo-HSCT recipients.

16.
Nat Commun ; 10(1): 5334, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31767869

RESUMO

Protein products of the regenerating islet-derived (REG) gene family are important regulators of many cellular processes. Here we functionally characterise a non-protein coding product of the family, the long noncoding RNA (lncRNA) REG1CP that is transcribed from a DNA fragment at the family locus previously thought to be a pseudogene. REG1CP forms an RNA-DNA triplex with a homopurine stretch at the distal promoter of the REG3A gene, through which the DNA helicase FANCJ is tethered to the core promoter of REG3A where it unwinds double stranded DNA and facilitates a permissive state for glucocorticoid receptor α (GRα)-mediated REG3A transcription. As such, REG1CP promotes cancer cell proliferation and tumorigenicity and its upregulation is associated with poor outcome of patients. REG1CP is also transcriptionally inducible by GRα, indicative of feedforward regulation. These results reveal the function and regulation of REG1CP and suggest that REG1CP may constitute a target for cancer treatment.

17.
Oncol Lett ; 18(5): 5163-5172, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31612027

RESUMO

The aim of the present study was to evaluate the potential network of arsenic trioxide (ATO) target genes in pancreatic cancer. The DrugBank, STITCH, cBioPortal, Kaplan-Meier plotter and Oncomine websites were used to analyze the association of ATO and its target genes with pancreatic cancer. Initially, 19 ATO target genes were identified, along with their associated protein-protein interaction networks and Kyoto Encyclopedia of Genes and Genomes pathways. ATO was found to be associated with multiple types of cancer, and the most common solid cancer was pancreatic cancer. A total of 6 ATO target genes (namely AKT1, CCND1, CDKN2A, IKBKB, MAPK1 and MAPK3) were found to be associated with pancreatic cancer. Next, the mutation information of the 6 ATO target genes in pancreatic cancer was collected. A total of 20 ATO interacting genes were identified, which were mainly involved in hepatitis B, prostate cancer, pathways in cancer, glioma and chronic myeloid leukemia. Finally, the genes CCND1 and MAPK1 were detected to be prognostic factors in patients with pancreatic cancer. In conclusion, bioinformatics analysis may help elucidate the molecular mechanisms underlying the involvement of ATO in pancreatic cancer, enabling more effective treatment of this disease.

18.
Zhongguo Zhen Jiu ; 39(10): 1081-6, 2019 Oct 12.
Artigo em Chinês | MEDLINE | ID: mdl-31621261

RESUMO

OBJECTIVE: To explore the action mechanism of electroacupuncture (EA) for knee osteoarthritis (KOA) based on Wnt/beta-catenin (Wnt/ß-catenin) signaling pathway. METHODS: Ten rats were randomly selected into a sham-operation group among 50 male 2-month-old SD rats, and the KOA model was established in the remaining 40 rats by modified Hulth method. Four weeks after the model establishment, the rats were randomly divided into a model group, an experimental A group, an experimental B group and an experimental C group, 10 rats in each group. The rats in the sham-operation group and model group did not receive any intervention. The rats in the experimental A group were treated with EA at "Neixiyan" (EX-LE 4) and "Dubi"(ST 35) for 15 min. The rats in the experimental B group were treated with EA at "Neixiyan" (EX-LE 4) and "Dubi"(ST 35) for 30 min. The rats in the experimental C group were treated with EA at non-acupoint for 15 min. EA intervention was given once a day, five times a week, and totally 12-week treatment was given. After 12 weeks, the knee cartilage tissues were stained and the morphological changes were observed under light microscopy; the severity of cartilage degeneration was evaluated by modified Mankin's score; the content of interleukin-1ß (IL-1ß) in synovium tissues was detected by ELISA method; the content of Wnt-4, ß-catenin and matrix metalloprotein-13 (MMP-13) in cartilage tissues was detected by Western blot method. RESULTS: Compared with the sham-operation group, in the model group the morphology and structure of cartilage were disordered, the number of cells was significantly reduced, the matrix was decontaminated and tidal line was incomplete; the Mankin's score was significantly increased (P<0.01), the content of IL-1ß in synovium tissues were significantly increased (P<0.01), and the expressions of Wnt-4, ß-catenin and MMP-13 at protein level were significantly increased (P<0.01). Compared with the model group, in the experimental A group and experimental B group the morphology and structure of cartilage were more orderly, the number of cells was increased, the matrix staining was deepened and the tidal line was more complete; Mankin's scores were decreased significantly (P<0.01); the contents of IL-1ß in synovium tissues were decreased significantly (P<0.01), and the expressions of Wnt-4, ß-catenin and MMP-13 at protein level were decreased significantly (P<0.01). Compared with the model group, no improvement was observed in the experimental C group. Compared with the experimental A group, in the experimental C group the morphology and structure of cartilage were disordered, the number of cells was significantly reduced, the matrix was decontaminated and the tidal line was incomplete; Mankin's score was significantly increased (P<0.01), the content of IL-1ß in synovium tissues was significantly increased (P<0.01), and the expressions of Wnt-4, ß-catenin and MMP-13 at protein level were significantly increased (P<0.01). The morphological structure of cartilage in the experimental B group was similar to that in the experimental A group, and there was no significant difference in Mankin's score, IL-1ß content in synovium tissues and the expressions of Wnt-4, ß- catenin and MMP-13 at protein level between the two groups (P>0.05). CONCLUSION: EA at "Neixiyan" (EX-LE 4) and "Dubi"(ST 35) may reduce the expression of MMP-13 and the production of inflammatory factor IL-1ß through Wnt/ß-catenin signaling pathway, thus inhibit the degradation of cartilage matrix and the apoptosis of chondrocyte, and improve the morphology and structure of cartilage.


Assuntos
Cartilagem Articular/metabolismo , Eletroacupuntura , Osteoartrite do Joelho , Via de Sinalização Wnt , Animais , Humanos , Masculino , Osteoartrite do Joelho/terapia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Transdução de Sinais
19.
Biomed Pharmacother ; 119: 109418, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31505423

RESUMO

YiQiFuMai Powder Injection (YQFM) is widely used in clinical practice for the treatment of heart failure (HF). However, its functional molecular mechanism remains to be fully uncovered. Our present study aimed to elucidate the impact of YQFM and underlying mechanisms on coronary artery ligation (CAL)-induced HF. Our results exhibited that YQFM significantly mitigated CAL-induced HF via meliorating the left ventricular contractile function and reducing the serum content of creatine kinase MB (CK-MB), aspartate aminotransferase (AST), interleukin-6 (IL-6), troponin (Tn), myosin, myoglobin (MYO) and myocilin (MYOC). Then, the relevance between circulating omentin level and cardiac function was investigated and we found that serum omentin levels positively associated with ejection fraction and negatively correlated with NT-proBNP content. Further, the effect of YQFM on cardiac function and omentin change in 1, 7 and 14 days CAL-induced HF mice was evaluated and the omentin secretion in isolated subcutaneous (SCAT) and epicardial adipose tissue (EAT) after YQFM treatment were detected. YQFM could increase the circulating omentin content both in 14 days CAL-induced HF mice and isolated EAT. And increased omentin in conditioned medium (CM) could inhibit simulated ischemic/reperfusion (SI/R)-induced cardiomyocytes apoptosis. Moreover, YQFM could ameliorate myocardial apoptosis via positive regulation of AMPK, PI3 K/Akt and negative regulation of MAPKs signaling pathways. Ginsenoside Rd might partially mediated omentin-dependent protective effect of YQFM. Our findings indicated that regulation of cross-talk between adipose tissue and cardiomyocytes might be a potential target through which YQFM exerts cardioprotective effect apart from direct cardiomyocytes protection.

20.
Front Pharmacol ; 10: 960, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31551773

RESUMO

In this study, a total of 58 patients with single subpleural pulmonary lesions (males: 36, females: 22, mean age: 63 ± 16.2 years) who underwent contrast-enhanced ultrasonography (CEUS) and had a definite diagnosis (benign lesions:25, malignant lesions:33) were enrolled. The number of biopsies, diagnostic accuracy rate, and the incidence of complications were recorded. The nodules were divided into two size subgroups: ≥5 cm (group 1), and <5 cm (group 2). The display rate of internal necrosis and change of pre-scheduled puncture paths were compared between subgroups. Also, the arrival times, intensity and uniformity of enhancement after the contrast agent injection, as well as the display rate of internal necrosis were recorded and compared between malignant and benign lesions. Finally, the average number of punctures was 2.9 ± 0.7 times. The total diagnosis rate was 98.3%. Local pneumothorax occurred in 2 patients. Hemoptysis occurred in 1 patient. No serious complications occurred. Internal necrosis was demonstrated in 20 of 58 lesions (34.5%). Sixteen of them had changed the planned puncture path due to the large necrosis area (80%, 16/20). For lesions in group 1, necrosis was found in 15 lesions and there was a statistically significant difference in the necrosis rate between the two subgroups (15/26 vs 5/32, p = 0.001). The change in the pre-scheduled puncture path occurred in 12 patients in group 1 while 4 patients in group 2 exhibited a change in the planned puncture path (p = 0.004). There was a statistically significant difference in the arrival times and intensity of enhancement between benign and malignant lesions (p < 0.05). In conclusion, CEUS guided biopsy is an effective, sensitive, and safe method for the diagnosis of pleural-based pulmonary lesions by facilitating a distinction between necrosis and active tissue. The current findings indicated that CEUS before a biopsy may be especially vital in lesions ≥5 cm.

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