Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 886
Filtrar
1.
J Cardiothorac Surg ; 15(1): 309, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33036645

RESUMO

OBJECTIVE: To investigate the effect of early oral stimulation with breast milk on the feeding behavior of infants after congenital cardiac surgery. METHODS: Infants with congenital heart disease were randomly divided into the breast milk oral stimulation group (n = 23), physiological saline oral stimulation group (n = 23) and control group (n = 23). Debra Beckman's oral exercise program was used with breast milk and physiological saline in the breast milk oral stimulation group and the physiological saline oral stimulation group, respectively. The time oral feeding and total oral nutrition were started, the length of intensive care unit (ICU) stay and hospital stay, weight and the complications at discharge were recorded for each group and statistically analyzed. RESULTS: The time oral feeding and total oral nutrition were started and the length of ICU stay and hospital stay were significantly less in the breast milk oral stimulation group and physiological saline oral stimulation group than in the control group (P < 0.05). There were no significant differences in other indicators between the breast milk oral stimulation group and the physiological saline oral stimulation group, except for the time total oral nutrition began (P < 0.05). However, there were no significant differences in weight or complications at discharge among the three groups (P > 0.05). CONCLUSION: Early oral stimulation exercises with breast milk can help infant patients quickly recover total oral nutrition and reduce the length of ICU and hospital stay after cardiac surgery.

2.
Drug Deliv ; 27(1): 1378-1385, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32998587

RESUMO

Herein, electrospun zinc oxide nanoparticle/poly (vinylidene fluoride) (ZnONP/PVDF) composite fiber membranes were designed, fabricated, and tested for improved orthopedic applications. A single factor screening study was conducted to determine the optimal ZnONP/PVDF formulation based on osteoblast (bone forming cells) proliferation and antibacterial properties. Further, ZnONP/PVDF materials were characterized for their morphology, crystallinity, roughness, piezoelectric properties, and chemistry to understand such cell results. The optimal concentration of high molecular weight PVDF (18%, w/v) and a low concentration of ZnONPs (1 mg/ml) were identified for electrospinning at room temperature in order to inhibit bacterial colonization (without resorting to antibiotic use) and promote osteoblast proliferation. Compared to no ZnO/PVDF scaffold without Piezo-excited group,the study showed that on the 1 mg/ml ZnO/PVDF scaffolds with piezo-excitation, the density of SA and E.coli decreased by 68% and 56%.The density of osteoblasts doubled within three days(compared to the control). In summary, ZnONP/PVDF composite fiber membranes were formulated by electrospinning showing an exceptional ability to eliminate bacteria colonization while at the same time promote osteoblast functions and, thus, they should be further studied for a wide range of orthopedic applications.

3.
J Vet Pharmacol Ther ; 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051869

RESUMO

This study aimed to examine the bioavailability (BA) and pharmacokinetic (PK) characteristics of sulfadiazine (SDZ) in grass carp (Ctenopharyngodon idellus) after oral and intravenous administrations. Blood samples were collected at predetermined time points of 0.083, 0.17, 0.5, 1, 2, 4, 8, 16, 24, 48, 72, and 96 hr (n = 6). The samples were extracted and purified by organic reagents and determined by the ultra-performance liquid chromatography. The software named 3P97 was used to calculate relevant PK parameters. The results demonstrated that the concentration-time profile of SDZ was best described by a one-compartmental open model with first-order absorption after a single oral dose. The main PK parameters of the absorption rate constant (Kα ), the absorption half-life (t1/2 Kα ), the elimination rate constant (Ke ), the elimination half-life (t1/2Ke ), and the area under concentration-time profile (AUC0-∞ ) were 0.3 1/h, 2.29 hr, 0.039 1/h, 17.64 hr, and 855.78 mg.h/L, respectively. Following intravenous administration, the concentration-time curve fitted to a two-compartmental open model without absorption. The primary PK parameters of the distribution rate constant (α), the elimination rate constant (ß), the distribution half-life (t1/2α ), the elimination half-life (t1/2ß ), the apparent distribution volume (VSS ), the total clearance (CL), and AUC0-∞ were 9.62 1/hr, 0.039 1/hr, 0.072 hr, 17.71 hr, 0.33 L/kg, 0.013 L h-1  kg-1 , and 386.23 mg.h/L, respectively. Finally, the BA was calculated to be 22.16%. Overall, this study will provide some fundamental information on PK properties in the development of a new formulation SDZ in the future and is partially beneficial for the appropriate usage of SDZ in aquaculture.

4.
Pharmacol Res ; : 105256, 2020 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-33086081

RESUMO

Phase 2 and phase 3 clinical studies showed that hypoxia-inducible factor prolyl hydroxylase inhibitors (HIF-PHIs) efficiently increased hemoglobin levels in both dialysis-dependent and non-dialysis-dependent chronic kidney disease (CKD) patients. However, the effects of HIF-PHIs on iron regulation have not been consistent among clinical trials. We performed a systematic review and meta-analysis of randomized controlled trials to evaluate the effects of six HIF-PHIs on iron regulation in non-dialysis CKD patients. Electronic databases were searched from inception to April 20, 2020, for eligible studies. Changes from baseline in transferrin saturation (TSAT), total iron-binding capacity (TIBC), iron, ferritin, and hepcidin levels were pooled using the inverse-variance method and presented as the mean difference (MD) or standardized MD (SMD) with 95 % confidence intervals (CIs). Meta-analysis of the included studies showed that, in non-dialysis-dependent CKD patients, HIF-PHIs decreased TSAT (MD, -4.51; 95 % CI, -5.81 to -3.21), ferritin (MD, -47.29; 95 % CI, -54.59 to -40.00) and hepcidin (SMD, -0.94; 95 % CI, -1.25 to -0.62), increased TIBC (MD, 9.15; 95 % CI, 7.08-11.22), and did not affect serum iron (MD, -0.31; 95 % CI, -2.05 to 1.42) despite enhanced erythropoiesis. This systematic review suggests that HIF-PHIs promote iron utilization in non-dialysis-dependent CKD patients. Importantly, HIF-PHIs are associated with increased transferrin levels (and TIBC), leading to reduced TSAT. Therefore, the reduction of TSAT after HIF-PHIs should not be interpreted as iron deficiency.

5.
Parasitol Res ; 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33094386

RESUMO

Gyrodactylid monogeneans are widespread parasites of teleost fishes, and infection with these parasites results in high host morbidity and mortality in aquaculture. To comprehensively elucidate the immune mechanisms against Gyrodactylus kobayashii, the transcriptome profiles of goldfish (Carassius auratus) skin after challenge with G. kobayashii were first investigated using next-generation sequencing. Approximately 21 million clean reads per library were obtained, and the average percentage of these clean reads mapped to the reference genome was 82.25%. A total of 556 differentially expressed genes (DEGs), including 344 upregulated and 212 downregulated genes, were identified, and 380 DEGs were successfully annotated and assigned to 95 signaling pathways in Kyoto Encyclopedia of Genes and Genomes (KEGG). In addition, 14 pathways associated with immune response were identified mainly including mTOR signaling pathway, cytokine-cytokine receptor interaction, intestinal immune network for IgA production, toll-like receptor signaling pathway, and phagosome. Twelve genes were selected and validated using qRT-PCR. A similar trend of these genes between RNA-Seq and qRT-PCR was observed, indicating that RNA-Seq data was reliable. Besides, the ALP activity and NO content in serum were significantly higher in the infected goldfish compared with the non-infected goldfish. In summary, this study provides better understandings of immune defense mechanisms of goldfish against G. kobayashii, which will support future molecular research on gyrodactylids and facilitate the prevention and treatment of gyrodactylosis in aquaculture.

6.
Front Endocrinol (Lausanne) ; 11: 545973, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33101193

RESUMO

Testosterone (T), predominantly acting through its derivative 17ß-estradiol (E2), regulates the brain's sexual differentiation in rodents during the perinatal sensitive period, which mirrors the window of vulnerability to the adverse effects of general anesthetics. The mechanisms of anesthesia's adverse effects are poorly understood. We investigated whether sevoflurane alters T and E2 levels and whether they contribute to sevoflurane's acute adverse effects in postnatal day 5 Sprague-Dawley rats. The rats underwent electroencephalography recordings for 2 h of baseline activity or for 1 h before and another hour during 2.1% sevoflurane exposure, followed by collection of trunk blood and brain tissue. Pharmacological agents, including the GABA type A receptor inhibitor bicuculline and the aromatase inhibitor formestane, were administered 30 min before sevoflurane anesthesia. Sevoflurane increased serum T levels in males only. All other effects of sevoflurane were similar in both sexes, including increases in serum levels of E2, hypothalamic mRNA levels of aromatase, estrogen receptor α (Erα) [not estrogen receptor ß (Erß)], Na+-K+-Cl- cotransporter (Nkcc1)/K+-Cl- cotransporter (Kcc2) mRNA ratio, electroencephalography-detectable seizures, and stress-like corticosterone secretion. Bicuculline and formestane alleviated these effects, except the T level increases. The ERα antagonist MPP, but not the ERß antagonist PHTPP, reduced electroencephalography-detectable seizures and normalized the Nkcc1/Kcc2 mRNA ratio. Collectively, sevoflurane exacerbates levels of T in males and E2 in both sexes during the period of their organizational effects in rodents. Sevoflurane acts through GABAAR-mediated, systemic T-independent elevation of E2 to cause electroencephalography-detectable seizures, stress-like corticosterone secretion, and changes in the expression of genes critical for brain development.

7.
J Int Med Res ; 48(10): 300060520962394, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33107372

RESUMO

Pulmonary blastoma (PB) is a very rare malignant lung tumor consisting of classic biphasic PB, well-differentiated fetal adenocarcinoma, and pleuropulmonary blastoma. We herein present an unusual case involving a patient with classic biphasic PB who underwent right upper lobe resection and subsequent treatment. No standard treatment guidelines are available for PB because of its rarity. Our patient received nedaplatin plus paclitaxel as adjuvant chemotherapy. After disease recurrence, the patient received two cycles of etoposide-cisplatin and six cycles of pemetrexed, bevacizumab, and carboplatin. Because of severe adverse effects of the chemotherapy, the patient was finally administered anlotinib, a new oral multikinase inhibitor. Both the tumor size and the serum tumor marker concentration decreased. In conclusion, surgical excision is the treatment of choice for PB. Chemotherapy in the present case resulted in PB activity that was consistent with the literature. Targeted therapies including antiangiogenic agents should be considered as a new treatment option for this rare disease.

9.
J Toxicol Sci ; 45(10): 625-637, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33012731

RESUMO

NOD-like receptor protein 3 (NLRP3) is involved in acute lung injury (ALI), but its exact role in phosgene-induced ALI is not clearly understood. The aim of the study is to explore the potential therapeutic effect of NLRP3 inflammasome modulation in the management of phosgene-induced ALI. ALI was induced in rats by phosgene exposure at 8.33 g/m3 for 5 min, 30 hr before intravenous injection of adenovirus-NLRP3 shRNA (Ad/NLRP3-shRNA). The histological changes in the lung were evaluated. Bronchoalveolar lavage fluid (BALF) neutrophils were counted (smear), and protein content was measured using the BCA assay. The wet/dry ratio of lung tissue (W/D) was measured. TUNEL staining for DNA damage was used to indirectly assess pyroptosis. NLRP3 inflammasome was assessed by immunohistochemistry, RT-PCR, western blotting. Cytokines were measured by ELISA. Histological analyses revealed reduced severity in phosgene-induced ALI with Ad/NLRP3-shRNA pretreatment. TUNEL staining indicated decreased pyroptosis in Psg-Ad/NLRP3-shRNA rats. Decreased mRNA and protein levels of NLRP3 and caspase-1 (all P < 0.05), but not ASC (P > 0.05), were found in Psg-Ad/NLRP3-shRNA rats. Immunohistochemistry revealed that Ad/NLRP3-shRNA pretreatment inhibited NLRP3 inflammasome activation. Reduced level of pro-inflammatory interleukin (IL)-1ß, IL-18, IL-33, and tumor necrosis factor (TNF)-α (all P < 0.05), but not of anti-inflammatory IL-4 and IL-10 (all P > 0.05), were found in serum and BALF from Ad/NLRP3-shRNA rats. NLRP3 gene silencing exerts beneficial effects on phosgene-induced lung injury by inhibiting NLRP3 inflammasome activation and pro-inflammatory factors, but not anti-inflammatory factors. Disruption of NLRP3 inflammasome activation might be used as a therapeutic modality for the treatment of phosgene-induced ALI.

10.
J Cardiothorac Surg ; 15(1): 256, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32933575

RESUMO

OBJECTIVE: To explore the effects of using the WeChat platform on the perioperative health education of parents of children who underwent transthoracic device closure of ventricular septal defects (VSDs). METHODS: Participants were divided into a WeChat group and a leaflet group. Responses to relevant questionnaires and clinical data were recorded and analyzed. RESULTS: Before the operation, the scores of the Caretaker Knowledge Questionnaire in the WeChat group were significantly higher than those in the leaflet group. The scores of PSQ-18 in the WeChat group were significantly higher than those in the leaflet group. All the children in the WeChat group were followed up 1 month after discharge, while four children in the leaflet group were lost to follow-up. The rate of attrition in the leaflet group was significantly higher than that in the WeChat group. For the postoperative complications, there was no significant difference between the two groups. CONCLUSION: Perioperative health education for parents of children who undergo transthoracic device closure of VSDs through the WeChat platform can effectively enhance parents' knowledge of care, improve parent satisfaction, which is an effective method to ensure convenient operation and reduce loss to follow-up.

11.
Mol Med Rep ; 22(4): 3117-3126, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32945469

RESUMO

Apolipoprotein M (apoM) may serve a protective role in the development of inflammation. Nuclear factor­κB (NF­κB) and its downstream factors (including a number of inflammatory cytokines and adhesion molecules) are essential for the regulation of inflammatory processes. In the present study, the importance of apoM in lipopolysaccharide (LPS)­induced acute inflammation and its potential underlying mechanisms, were investigated using an apoM­knockout mouse model. The levels of inducible nitric oxide synthase (iNOS), NF­κB, interleukin (IL)­1ß, intercellular adhesion molecule 1 (ICAM­1) and vascular cell adhesion protein 1 (VCAM­1) were detected using reverse transcription­quantitative PCR and western blotting. The serum levels of IL­6 and IL­10 were detected using Luminex technology. The results demonstrated that the protein levels of iNOS, NF­κB, IL­1ß, ICAM­1 and VCAM­1 were significantly increased in apoM­/­ mice compared with those in apoM+/+ mice. In addition, two­way ANOVA revealed that the interaction between apoM and LPS had a statistically significant effect on a number of factors, including the mRNA expression levels of hepatic iNOS, NF­κB, IL­1ß, ICAM­1 and VCAM­1. Notably, the effects of apoM and 10 mg/kg LPS on the levels of IL­6 and IL­10 were the opposite of those induced by 5 mg/kg LPS, which could be associated with the dual anti­ and pro­inflammatory effects of IL­6 and IL­10. Collectively, the results of the present study revealed that apoM is an important regulator of inflammatory cytokine and adhesion molecule production in LPS­induced inflammation, which may consequently be associated with the severity of inflammation. These findings indicated that the anti­inflammatory effects of apoM may partly result from the inhibition of the NF­κB pathway.

12.
J Cardiothorac Surg ; 15(1): 281, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32993714

RESUMO

OBJECTIVE: To investigate the effect of remifentanil-based fast-track anesthesia on analgesia and sedation after transthoracic device closure of ventricular septal defects (VSDs) in adult patients. METHODS: A retrospective analysis was performed on 59 patients aged 21-53 years who underwent transthoracic device closure of VSDs from January 2019 to September 2019. According to the different anesthesia strategies, the patients were divided into the R group (using remifentanil-based anesthesia, n = 33) and the S group (using sufentanil-based anesthesia, n = 26). Patient-related clinical data, postoperative analgesia, and sedation scores were collected and analyzed. RESULTS: There was no significant difference in age, gender, body weight, and operation time between the group R and the group S (P > 0.05). There was also no significant difference in intraoperative hemodynamic changes, BIS scores, postoperative analgesia, and sedation scores between the two groups (P > 0.05). The duration of mechanical ventilation, the length of ICU stay, and hospital stay in the group R were significantly lower than those in the group S (P < 0.05). CONCLUSION: Remifentanil-based fast-track anesthesia is effective for adult patients undergoing transthoracic device closure of VSDs, which may shorten the mechanical ventilation duration, the ICU and hospital stay of patients.

13.
Genomics ; 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32979493

RESUMO

OBJECTIVE: To screen several immune-related long non-coding RNAs (lncRNAs) and construct a prognostic model for papillary renal cell carcinoma (pRCC). METHODS: Transcriptome-sequencing data of pRCC was downloaded and a prognostic model was constructed. Time-dependent receiver operating characteristic (ROC) curve was plotted and the area under curve (AUC) was calculated. We conducted quantitative reverse transcription polymerase chain reaction (RT-PCR) to verify the model. The gene set enrichment analysis (GSEA) was used to show the connection of our model with immune pathways. RESULT: We identified four lncRNAs to constructed the model. The model was significantly associated with the survival time and survival state. The expression-levels of the four lncRNAs were measured and the prognosis of high-risk patients was significantly worse. The two immune-gene sets had an active performance in the high-risk patients. CONCLUSION: We constructed a prognostic model in pRCC which provided more reference for treatment.

14.
Artigo em Inglês | MEDLINE | ID: mdl-32893225

RESUMO

OBJECTIVE: To explore the health-related quality of life (HRQoL) of children and adolescents with simple congenital heart defects before and after the transcatheter intervention. METHODS: The Pediatric Quality of Life Inventory 4.0 scale was used to assess the quality of life of 78 children and adolescents before and after the transcatheter intervention and to evaluate the parents' perception of their children's quality of life. RESULTS: In all, 76 patients were completed the study. The results showed that the scores of the four dimensions and the total score for the quality of life of the patients significantly improved 1 month after the intervention. At 6 months after treatment, the scores in all dimensions continued to improve. From the parents' perspective, the scores of the patients in all dimensions improved significantly at 1 month and 6 months after treatment. In terms of the quality of life assessment, the self-assessment results of the patients were more positive than those of their parents. CONCLUSIONS: The results showed that the quality of life of children and adolescents with simple congenital heart defects can be positively affected by the transcatheter intervention. Moreover, this improvement is not transient and seems to increase over time.

15.
Sheng Wu Gong Cheng Xue Bao ; 36(8): 1568-1577, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32924355

RESUMO

Catalase catalyzes the decomposition of H2O2 to H2O and O2, and has a wide range of industrial applications. However, most catalases used in the textile and paper industries are often subjected to high-alkaline challenges which makes it necessary to develop alkaline catalase. In this study, a catalase from Corynebacterium glutamicum was expressed in Escherichia coli, and the expression conditions were optimized. The recombinant catalase was purified by Ni-chelating affinity chromatography, and the recombinant enzyme was characterized. The optimal conditions of producing the recombinant catalase were: an IPTG concentration of 0.2 mmol/L, a culturing temperature of 25 °C and a culturing time of 11 h. The purified catalase had a specific activity of 55 266 U/mg, and it had a high activity in the pH range of 4.0 to11.5, with the highest activity at pH 11.0. When treated in pH 11.0 for 3 h, the enzyme retained 93% of its activity, indicating that the enzyme was qualified with a favorable stability under high-alkaline condition. The recombinant catalase had maximal activity at 30 °C, and showed a satisfactory thermal stability at a range of 25 °C to 50 °C. The apparent Km and Vmax values of purified catalase were 25.89 mmol/L and 185.18 mmol/(minmg), respectively. Besides, different inhibitors, such as sodium dodecyl sulfate (SDS), urea, NaN2, ß-mercaptoethanol, and EDTA had different degrees of inhibition on enzyme activity. The catalase from C. glutamicum shows high catalytic efficiency and high alkaline stability, suggesting its potential utilization in industrial production.


Assuntos
Catalase , Corynebacterium glutamicum , Regulação Enzimológica da Expressão Gênica , Catalase/genética , Catalase/isolamento & purificação , Catalase/metabolismo , Corynebacterium glutamicum/enzimologia , Ativação Enzimática , Estabilidade Enzimática , Concentração de Íons de Hidrogênio
16.
Anesth Analg ; 131(4): 1291-1299, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32925350

RESUMO

BACKGROUND: Neonatal exposure to sevoflurane induces neurobehavioral and neuroendocrine abnormalities in exposed male rats (generation F0) and neurobehavioral, but not neuroendocrine, abnormalities in their male, but not female, offspring (generation F1). These effects of sevoflurane are accompanied by a hypermethylated neuron-specific K-2Cl (Kcc2) Cl exporter gene in the F0 spermatozoa and the F1 male hypothalamus, while the gene's expression is reduced in the F0 and F1 hypothalamus. We investigated whether inhibition of deoxyribonucleic acid methyltransferases (DNMTs) before paternal sevoflurane exposure could alleviate the anesthetic's F0 and F1 effects. METHODS: Sprague-Dawley male rats were anesthetized with 2.1% sevoflurane for 5 hours on postnatal day (P) 5 and mated with control females on P90 to generate offspring. The nonselective DNMT inhibitor decitabine (0.5 mg/kg, intraperitoneally) was administered 30 minutes before sevoflurane exposure. The F0 and F1 male rats were evaluated in in vivo and in vitro tests in adulthood. RESULTS: Paternal exposure to sevoflurane induced impaired prepulse inhibition of the acoustic startle response and exacerbated corticosterone responses to stress in F0 males and impaired prepulse inhibition of the startle responses in F1 males. These effects were accompanied in both generations by reduced and increased expressions of hypothalamic Kcc2 and Dnmt3a/b, respectively. Decitabine deterred the effects of paternal exposure to sevoflurane in F0 and F1 males. CONCLUSIONS: These results suggest that similar decitabine-sensitive mechanisms regulating expression of multiple genes are involved in the mediation of neurobehavioral abnormalities in sires neonatally exposed to sevoflurane and in their future unexposed male offspring.

17.
Diabetes Obes Metab ; 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32965075

RESUMO

AIM: To evaluate the efficacy and safety of polyethylene glycol loxenatide (PEX168) monotherapy in type 2 diabetes (T2D) patients in China. MATERIALS AND METHODS: In a multicentred, randomized, double-blinded, placebo-controlled phase 3a clinical trial, 361 patients with inadequate glycaemic control (HbA1c 7.0%-10.5%, fasting plasma glucose <13.9 mmol/L) were randomized (1:1:1) for weekly subcutaneous injections: placebo, PEX168/100 µg or PEX168/200 µg. The 24-week treatment was followed by a 28-week extension, during which placebo-treated patients were randomly assigned to PEX168/100 µg or PEX168/200 µg. The primary efficacy endpoint was the HbA1c change from baseline to week 24. RESULTS: The three groups had similar demographics and baseline characteristics. The HbA1c least-square mean (95% CI) change from baseline to week 24 was greater for PEX168/100 µg (-1.02% [-1.21%, -0.83%]) and PEX168/200 µg (-1.34% [-1.54%, -1.15%]) than for placebo (-0.17% [-0.36%, 0.02%]); (superiority: P < .0001). The proportions of patients with less than 7% HbA1c in the placebo, PEX168/100 µg and PEX168/200 µg groups were 15.7%, 34.7% and 46.6%, respectively. Common gastrointestinal adverse events (AEs) were nausea (5.6%, 10.0% and 0% for PEX168/100 µg, PEX168/200 µg and placebo, respectively) and vomiting (2.4%, 8.3% and 0% for PEX168/100 µg, PEX168/200 µg and placebo, respectively). Six (1.6%) patients (PEX168/100 µg: N = 2 [1.6%], PEX168/200 µg: N = 3 [2.5%] and placebo: N = 1 [0.8%]) discontinued treatment because of AEs. Four (1.2%) patients (PEX168/100 µg: N = 3 [2.5%] and PEX168/200 µg: N = 1 [0.9%]) developed PEX168 antidrug antibodies. CONCLUSION: PEX168 monotherapy significantly improved glycaemic control in T2D patients with a safety profile resembling that of other glucagon-like peptide-1 receptor agonists.

18.
Mol Plant ; 13(10): 1499-1512, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32977056

RESUMO

Plasma membrane-localized receptor-like kinases (RLKs) perceive conserved pathogen-associated molecular patterns (PAMPs) in plants, leading to PAMP-triggered immunity (PTI). The Arabidopsis thaliana lectin RLK LecRK-IX.2 has been shown to regulate the bacterial flagellin-derived peptide flg22-induced PTI. Here, we discover that Pseudomonas syringae effector AvrPtoB targets LecRK-IX.2 for degradation, which subsequently suppresses LecRK-IX.2-mediated PTI and disease resistance. However, LecRK-IX.2 can interact with and phosphorylate AvrPtoB at serine site 335 (S335). AvrPtoB self-associates in vitro and in vivo, and the association appears to be essential for its E3 ligase activity in ubiquitinating substrate in plants. Phosphorylation of S335 disrupts the self-association and as a result, phosphomimetic AvrPtoBS335D cannot ubiquitinate LecRK-IX.2 efficiently, leading to the compromised virulence of AvrPtoB in suppressing PTI responses. flg22 enhances AvrPtoB S335 phosphorylation by inducing the expression and activating of LecRK-IX.2. Our study demonstrates that host RLKs can modify pathogen effectors to dampen their virulence and undermine their ability in suppressing PTI.

19.
Biochem Biophys Res Commun ; 530(1): 189-195, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32828284

RESUMO

Phosgene-induced lung injury is an important type of acute lung injury (ALI). Currently, no effective clinical treatment has been developed yet. Our previous study revealed that expressions of 6 miRNAs were significantly increased in phosgene-induced lung injury. The screened miRNA with the most significant effect on hepatocyte growth factor (HGF) expression by mesenchymal stem cells (MSCs) was transfected into MSCs. This study aimed to investigate whether the transfected MSCs had better therapeutic effects than MSCs alone. MSCs were co-cultured with miRNA mimics for 24h and 48h. HGF expression in culture supernatant was detected by ELISA. HGF expression in MSCs was detected by Western blot after being co-cultured with the selected miRNA inhibitor. The transfected MSCs were given to rats suffering from phosgene-induced lung injury. Expressions of TNF-α, IL-6, IL-1ß and IL-10, were assayed by ELISA. SP-C mRNA level was tested by RT-PCR. VE-CAD expression was tested by Western blot. We found that miRNA-378a-5p most increased HGF expression among the six miRNAs. After transfection of MSCs with miRNA-378a-5p inhibitor, HGF expression was decreased. Compared with untreated MSCs, MSCs transfected with miRNA-378a-5p exhibited more significant decreases in lung injury score, white blood cell count and protein content while restoring respiratory indexes. Meanwhile, expressions of TNF-α, IL-6, IL-1ß were decreased while those of IL-10, SP-C and VE-cadherin were increased. In conclusion, MSCs transfected with miRNA-378a-5p were more effective in treating phosgene-induced lung injury by repairing the secretion of alveolar epithelial cells and improving the permeability of vascular endothelial cells compared with MSCs alone.

20.
Cancer Manag Res ; 12: 5491-5503, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32765063

RESUMO

Objective: Colorectal cancer (CRC) is one of the most common malignant tumors in the digestive tract, which accounts for 10% of all the malignant tumors in the world. The aim of this study was to identify key genes and miRNAs in CRC diagnosis, prognosis, and therapy and to further explore the potential molecular mechanisms of CRC. Methods: The infiltration and metastasis of neutrophils in primary colorectal cancer tissue and paracancerous tissue were observed by immunohistochemical staining. After inducing N2 neutrophils with TGF-ß1 in vitro, exosomes were extracted and sequenced, and then the expression differences of miRNAs were screened by using Agilent miRNA microarrays. The data were imported to the Web CARMA for differential expression analysis. The GO and KEGG enrichment analysis were performed using DIANA-MirPath v3.0 using TargetScan database. And the corresponding targets were imported into Gephi for network analysis. The expression level of differentially expressed miRNA using quantitative real-time polymerase chain reaction (RT-PCR) was validated. Results: A total of 2 miRNAs were found to be associated with N2 neutrophils, in which the expression of hsa-miR-4780 was upregulated and the expression of hsa-miR-3938 was downregulated in N2 neutrophils, compared with the neutrophils. In addition, the results of miRNA-targets networks showed that the hsa-mir-3938 and hsa-mir-4780 could regulate TUSC1 and ZNF197. The expression level of hsa-miR-4780 and hsa-miR-3938 wase validated in accordance with the results of RT-PCR. Conclusion: The hsa-mir-3938 and hsa-mir-4780 were differentially expressed between N2 neutrophils and neutrophils. Moreover, the regulation of TUSC1 and ZNF197 by these DEmiRNA established the theoretical basis for the mechanism of N2 type neutrophils regulating the invasion and metastasis of CRC cells and provided the potential biomarker for prognosis for clinical treatment of CRC.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA