Porphyromonas gingivalis (P. gingivalis) is the most common species that causes peri-implantitis. It forms an irreversible dense biofilm and causes inflammation. A novel 3D-printed porous TC4-6Cu alloy was fabricated using selective laser melting (SLM) technology for the dental implant, which is anticipated to inhibit biofilm formation. We attempted to investigate the antibacterial ability and antibacterial mechanism of the 3D-printed porous TC4-6Cu alloy against P. gingivalis. This work used scanning electron microscopy (SEM) and laser confocal microscopy (CLSM) to detect the antimicrobial ability of the alloy against sessile P. gingivalis. The results indicated that the 3D-printed porous TC4-6Cu alloy could cause bacterial fragmentation and deformation. Plate antimicrobial counting experiments showed that the antibacterial rates of the alloy against adherent bacteria and planktonic bacteria after 24 h were 98.05% and 73.92%, respectively. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Cu2+ were tested to appraise the antibacterial property of the alloy against planktonic P. gingivalis. The relationship between the antibacterial mechanism of the alloy with oxidative stress was evaluated through ROS fluorescence intensity and protein leakage concentration. The results revealed that the alloy significantly eliminated adherent bacteria and inhibited biofilm formation. Moreover, 3D-printed porous TC4-6Cu alloy demonstrated significant bactericidal ability by inducing the production of reactive oxygen species (ROS), which could result in protein leakage from the bacterial cell membrane. This research may open a new perspective on the development and biomedical applications for dental implantation.
Background Acute megakaryoblastic leukemia (AMKL) without Down syndrome (non-DS-AMKL) usually a worse outcome than DS-AMKL. Acquired trisomy 21(+21) was one of the most common cytogenetic abnormalities in non-DS-AMKL. Knowledge of the difference in the clinical characteristics and prognosis between non-DS-AMKL with +21 and those without +21 is limited.Objective Verify the clinical characteristics and prognosis of non-DS-AMKL with +21.Method We retrospectively analyzed 33 non-DS-AMKL pediatric patients and 118 other types of AML, along with their clinical manifestations, laboratory data, and treatment response.Results Compared with AMKL without +21, AMKL with +21 has a lower platelet count (44.04 ± 5.01G/L) at onset (P > 0.05). Differences in remission rates between AMKL and other types of AML were not significant. Acquired trisomy 8 in AMKL was negatively correlated with the long-term OS rate (P < 0.05), while +21 may not be an impact factor. Compared with the other types of AML, AMKL has a younger onset age (P < 0.05), with a mean of 22.27 months. Anemia, hemorrhage, lymph node enlargement, lower white blood cell, and complex karyotype were more common in AMKL (P < 0.05). AMKL has a longer time interval between onset to diagnosis (53.61 ± 71.15 days) (P < 0.05), and patients with a diagnosis delay ≥3 months always presented as thrombocytopenia or pancytopenia initially.Conclusions Due to high heterogeneity, high misdiagnosis rate, and myelofibrosis, parts of AMKL may take a long time to be diagnosed, requiring repeated bone marrow punctures. Complex karyotype was common in AMKL. +21 may not be a promising indicator of a poor prognosis.
Cordyceps sinensis is a traditional Chinese herbal medicine that has been used for centuries in Asia as a tonic to soothe the lung for the treatment of respiratory diseases. The aim of the present study was to determine the effects of C. sinensis on airway remodeling in chronic obstructive pulmonary disease (COPD) and investigate the underlying molecular mechanisms. Rats with COPD were orally administered C. sinensis at low, moderate or high doses (2.5, 5 or 7.5 g/kg/day, respectively) for 12 weeks. Airway tissue histopathology, lung inflammation and airway remodeling were evaluated. C. sinensis treatment significantly ameliorated airway wall thickening, involving collagen deposition, airway wall fibrosis, smooth muscle hypertrophy and epithelial hyperplasia in model rats with COPD. Additionally, C. sinensis administration in rats with COPD reduced inflammatory cell accumulation and decreased inflammatory cytokine production, including tumor necrosis factor‑α, interleukin‑8 and transforming growth factor (TGF)‑β1 in bronchoalveolar lavage fluid. Meanwhile, the increased levels of α‑smooth muscle actin and collagen I in the COPD group were also markedly decreased by C. sinensis treatment. Furthermore, compared with untreated rats with COPD, C. sinensis reduced the expression level of phosphorylated (p)‑Smad2, p‑Smad3, TGF‑β1 and its receptors, with the concomitant increased expression of Smad7 in the lungs of rats with COPD. These results indicated that treatment with C. sinensis may be a useful approach for COPD therapy.
Aurora-A has attracted a great deal of interest as a potential therapeutic target for patients with CRC. However, the outcomes of inhibitors targeting Aurora-A are not as favorable as expected, and the basis behind the ineffectiveness remains unknown. Here, we found that signal transducer and activator of transcription 1 (STAT1) was highly expressed in colorectal cancer (CRC) xenograft mouse models that were resistant to alisertib, an Aurora-A inhibitor. Unexpectedly, we found that alisertib disrupted Aurora-A binding with ubiquitin-like with plant homeodomain and ring finger domain 1 (UHRF1), leading to UHRF1 mediated ubiquitination and degradation of DNA methyltransferase 1 (DNMT1), which in turn resulted in demethylation of CpG islands of STAT1 promoter and STAT1 overexpression. Simultaneous silencing Aurora-A and UHRF1 prevented STAT1 overexpression and effectively inhibited CRC growth. Hence, concomitant targeting Aurora-A and UHRF1 can be a promising therapeutic strategy for CRC.
This meta-analysis mainly aimed to compare the impact of prasugrel and ticagrelor on platelet reactivity (PR) in patients with acute coronary syndrome (ACS).We searched four electronic databases to identify randomized controlled trials and cohort studies comparing the impact of prasugrel and ticagrelor on PR in patients with ACS. We performed group analyses according to three detection methods, drug dose [loading dose (LD) and maintenance dose (MTD)] and LD effect time, and assessed the robustness of the results through sensitivity analysis.Twenty-five studies with 5,098 patients were eligible. After LD, the incidence of high on-treatment platelet reactivity (HTPR) of ticagrelor was significantly lower than that of prasugrel within 6-18 h based on vasodilator-stimulated phosphoprotein (VASP) test [RR = 0.25 (0.07, 0.85), P = 0.03], there was no significant difference between ticagrelor and prasugrel in the following results: platelets inhibitory effect within 24-48 h based on VerifyNow P2Y12 (VN) assay (P = 0.11) and VASP test (P = 0.20), and the incidence of HTPR within 2-6 h based on VN assay (P = 0.57) and within 24-48 h based on VN assay (P = 0.46) and VASP test (P = 0.72), the incidence of low on-treatment platelet reactivity (LTPR) within 6-18 h based on VASP test (P = 0.46) and 48 h based on VN assay (P = 0.97) and VASP test (P = 0.73). After MTD, the platelet inhibitory effect of ticagrelor was stronger than that of prasugrel based on VN assay [WMD = -41.64 (-47.16, -36.11), P < 0.00001]and VASP test [WMD = -9.10 (-13.88, -4.32), P = 0.0002], the incidence of HTPR of ticagrelor was significantly lower than that of prasugrel based on VN assay [RR = 0.05 (0.02, 0.16), P < 0.00001], the incidence of LTPR of ticagrelor was significantly higher than prasugrel based on VN assay [RR = 6.54 (4.21, 10.14), P < 0.00001] and VASP test [RR = 2.65 (1.78, 3.96), P < 0.00001], the results of Multiple Electrode Aggregometry (MEA) test was inconsistent with the other two detection methods in platelet inhibitory effect and the incidence of HTPR and LTPR. There was no significant difference between ticagrelor and prasugrel in the following clinical outcomes: all-cause death (P = 0.86), cardiovascular death (P = 0.49), myocardial infarction (P = 0.67), stroke (P = 0.51), target vessel revascularization (P = 0.51), stent thrombosis (P = 0.90), TIMI major bleeding (P = 0.86) and bleeding BARC type ≥ 2 (P = 0.77). The risk of bleeding BARC type 1 of ticagrelor was significantly higher than prasugrel [RR = 1.44 (1.03, 2.02), P = 0.03].Compared with prasugrel, ticagrelor might have a stronger platelet inhibition effect, with a lower incidence of HTPR and a higher incidence of LTPR and bleeding BARC type 1, while there might be no significant difference in the risk of thrombosis/ischemic, bleeding BARC Type ≥ 2 and TIMI major bleeding. A higher incidence of LTPR might indicate a higher risk of bleeding BARC type 1. The results of VN assay were consistent with that of VASP test, and not with the MEA test.https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022304205, identifier: CRD42022304205.
Abstract Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency–Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.
Abstract In the early 2000s, emerging SARS‐CoV‐2, which is highly pathogenic, posed a great threat to public health. During COVID‐19, epigenetic regulation is deemed to be an important part of the pathophysiology and illness severity. Using the Illumina Infinium Methylation EPIC BeadChip (850 K), we investigated genome‐wide differences in DNA methylation between healthy subjects and COVID‐19 patients with different disease severities. We conducted a combined analysis and selected 35 “marker” genes that could indicate a SARS‐CoV‐2 infection, including 12 ( ATHL1 , CHN2 , CHST15 , CPLX2 , CRHR2 , DCAKD , GNAI2 , HECW1 , HYAL1 , MIR510 , PDE11A , and SMG6 ) situated in the promoter region. The functions and pathways of differentially methylated genes were enriched in biological processes, signal transduction, and the immune system. In the “Severe versus Mild” group, differentially methylated genes, after eliminating duplicates, were used for PPI analyses. The four hub genes ( GNG7 , GNAS , PRKCZ , and PRKAG2 ) that had the highest degree of nodes were identified and among them, GNG7 and GNAS genes expressions were also downregulated in the severe group in sequencing results. Above all, the results suggest that GNG7 and GNAS may play a non‐ignorable role in the progression of COVID‐19. In conclusion, the identified key genes and related pathways in the current study can be used to study the molecular mechanisms of COVID‐19 and may provide possibilities for specific treatments.
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