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Pseudouridine synthase 7 (PUS7) may play key roles in cancer development. However, few studies have been conducted in this area. In the present study, we explored the function and potential mechanisms of PUS7 in colorectal cancer (CRC) progression. We found that PUS7 had higher expression in CRC tissues and cell lines. Clinically, high expression of PUS7 was associated with an unfavorable prognosis for CRC patients. Functionally, knockdown of PUS7 suppressed the proliferation of CRC cells in vitro and inhibited tumorigenicity in vivo. Mechanistically, RNA sequencing and coimmunoprecipitation (Co-IP) indicated that PUS7 exhibited oncogenic functions through the interaction of Sirtuin 1 (SIRT1) and activated the Wnt/β-catenin signaling pathway. Thus, our findings suggest that PUS7 promotes the proliferation of CRC cells by directly stabilizing SIRT1 to activate the Wnt/β-catenin pathway.Improved Ca2+ sensitivity has been suggested as a mechanism behind enhancements in muscle mechanical function following eccentric training. However, little is known regarding the effects of eccentric training on single muscle fiber Ca2+ sensitivity. Adult male Sprague-Dawley rats (sacrificial age ~18 weeks; mass = 400.1 ± 34.8 g) were assigned to an eccentric training (n = 5) or sedentary control group (n = 6). Eccentric training consisted of 4 weeks of weighted downhill running 3×/week at a 15° decline and 16 m/min for 35 min per day in 5-min bouts. After sacrifice, vastus intermedius single muscle fibers were dissected, chemically permeabilized, and stored until testing. Fibers (n = 63) were isolated, and standard Ca2+ sensitivity, force, rate of force redevelopment (ktr ), and active instantaneous stiffness tests were performed using [Ca2+ ] ranging from 7.0 to 4.5. Following all mechanical testing, fiber type was determined using SDS-PAGE. There was no difference in pCa50 (i.e., [Ca2+ ] needed to elicit half of maximal force) between groups or between fiber types. However, when comparing normalized force across pCa values, fibers from the control group produced greater forces than fibers from the trained group at lower Ca2+ concentrations (p less then  0.05), and this was most evident for Type I fibers (p = 0.002). Type II fibers produced faster (p  less then  0.001) ktr than Type I fibers, but there were no differences in absolute force, normalized force, or other measures of mechanical function between fibers from the trained and control groups. These findings indicate that eccentric training does not appear to improve single muscle fiber Ca2+ sensitivity.A simple pyridine-based compound, i.e. (2,4,6-tris(4-(hexyloxy)phenyl)pyridine), was synthesized and exhibited excellent solubility in various organic solvents owing to the presence of three 4-n-hexyloxy chains in its molecular structure. Further, we studied the effect of various solvents on its absorption and emission properties. We observed a greater extent of redshift in the chloroform solvent compared to the rest of the solvents. In fact, the observed redshift was attributed to protonation of the pyridine moiety by HCl (present due to the oxidative photo-decomposition of chloroform) in the solvent. Therefore, we also studied the acidochromic properties of the compound using acetic acid (AA), trifluoroacetic acid (TFA), and hydrochloric acid (HCl). We found that the compound sensed the HCl vapor much more efficiently than the TFA and AA vapours. Additionally, DFT analysis suggested a narrow theoretical bandgap for the protonated molecule when compared to the neutral molecule, explaining the redshift in the absorption and emission spectra of the protonated molecule. Furthermore, the compound exhibited a good level of aggregation induced enhanced emission (AIEE) in the THF-water system. In fact, compounds showing both AIEE and acidochromism are rarely reported in the literature. Finally, we employed it as an anti-counterfeiting agent based on its acid-base vapour sensing capability.

Lupus anticoagulant (LA) testing requires normal pooled plasma (NPP) in performing mixing studies and can be used for normalized ratios of clotting times (CTs). The aims were to demonstrate whether significant differences in clotting times between two batches of a same commercial NPP (CRYOcheck™) directly affect NPP-based cut-off values.

Diluted Russell Viper venom time (DRVVT) and activated partial thromboplastin time (aPTT) were used for LA testing. Screening, mixing and confirm tests were performed with Stago® instruments and reagents. Two batches of commercial NPP (A1291 and A1301 from CRYOcheck™; frozen) were compared in the determination of cut-off values. Cut-off values were defined as 99th percentile values of 60 healthy donors and compared with Mann-Whitney U test.

Cut-off values obtained with the two NPP batches were significantly different for DRVVT (screen normalized ratio 1.09 vs. 1.24, screen mix 41.9s vs. 38.9 s; index of circulating anticoagulant 5.0 vs. 8.4; all had p-value <.001). On the contrary, no significant differences were observed for aPTT (screen normalized ratio 1.32 vs. 1.34; p-value=.4068, screen mix 37.8s vs. 38.1 s; p-value=.1153) except for index of circulating anticoagulant 9.6 versus 10.4 (p-value <.05).

This study demonstrates that differences between two commercial NPP batches produced by a same manufacturer influenced LA cut-off values used for mixing studies and normalized ratios. Adequate cut-off setting, taking into account NPP CTs, is important to provide accurate conclusion about the presence or absence of a LA and avoid potential clinical impact.

This study demonstrates that differences between two commercial NPP batches produced by a same manufacturer influenced LA cut-off values used for mixing studies and normalized ratios. Adequate cut-off setting, taking into account NPP CTs, is important to provide accurate conclusion about the presence or absence of a LA and avoid potential clinical impact.Seminoma is the most common type of testicular germ cell tumour and is highly sensitive to cisplatin therapy, which has not been fully elucidated. In this study, we comprehensively monitored dynamic changes of TCam-2 cells after cisplatin treatment. At an early stage, we found that both low and high concentrations of cisplatin induced the S-phase arrest in TCam-2 cells. By contrast, the G0G1 arrest was caused by cisplatin in teratoma NTERA-2 cells. Afterwards, high concentrations of cisplatin promoted the extrinsic apoptosis and high expressions of related genes (Fas/FasL-caspase-8/-3) in TCam-2 cells. However, when decreasing the cisplatin, the apoptotic cells were significantly reduced, and accompanied by cells showing senescence-like morphology, positive SA-β-gal staining and up-regulation of senescence-related genes (p53, p21 and p16). Furthermore, the cell cycle analysis revealed that most of the senescent TCam-2 cells were irreversibly arrested in the G2M phase. G2M arrest was also observed in NTERA-2 cells treated with a low concentration of cisplatin, while no senescence-related phenotype was discovered. In addition, we detected the γ-H2AX, a DNA damage marker protein, and reactive oxygen species (ROS) and found both of which were elevated with the increase of cisplatin in TCam-2 cells. In conclusion, the extrinsic apoptosis and senescence are involved in the growth kinetics of TCam-2 cells to cisplatin, which provide some implications for studies on cisplatin and seminoma.Diabetes mellitus is a widespread endocrine disorder globally. Due to its antioxidant and anti-inflammatory properties, ellagic acid has the potential to improve the metabolic effects of chronic non-communicable diseases. This systematic review summarizes current evidence about the potential effects of ellagic acid on metabolic variables in diabetes mellitus. A comprehensive systematic literature search was conducted in databases such as PubMed, Scopus, EMBASE, ProQuest and Google Scholar from inception until March 2022. All animal studies and clinical trials were eligible for inclusion. Studies using in vitro models or published in a non-English language were excluded. Of 1320 articles, 23 were selected for assessment, including 21 animal studies and two randomized controlled trial studies. Protosappanin B mw Following ellagic acid administration, findings reported improvement in FBS, HbA1c, insulin (20, 8 and 12 studies, respectively), TG, TC, HDL-C (13, 10 and 5 studies, respectively), MDA, GSH, CAT, SOD (11, 6, 3 and 4 studies, respectively), and TNF-α and IL-6 (6 and 3 studies, respectively). In conclusion, ellagic acid may improve glycaemic indicators, dyslipidaemia, oxidative stress and inflammation in diabetes mellitus. However, further clinical trials are needed to explore the mechanisms more precisely and to observe the applied consequences.The increment of platelet aggregation factors has been considered a key phenomenon in atherosclerosis. Studies have shown that garlic (Allium sativum) is associated with a reduction in platelet aggregation and thrombosis. Hence, the present systematic review was conducted to evaluate the effect of garlic on platelet aggregation. All randomized controlled trials (RCTs) with keywords related to garlic and platelet aggregation were thoroughly searched in electronic databases including PubMed, Scopus, ISI Web of Science, and Google Scholar up to January 2021. Moreover, the references of all related articles were screened to discover more relevant studies. The quality of each study was reported based on Cochrane Collaboration's tool. In total, 12 studies met the inclusion criteria from 18,235 identified articles (including 595 participants). Most of the studies assessed platelet aggregation in response to different inducers. Of the 12 clinical trials, six studies depicted the beneficial effect of garlic on reducing platelet aggregation. The summary of the quality assessment indicated that most of the studies had high-quality scores. Regarding the small number of RCTs and heterogeneity between studies, it is impossible to make a proper conclusion about the impacts of garlic on platelet aggregation. Therefore, further precise trials with a standard design are necessary to validate the anti-thrombotic effect of garlic.

Pharmacokinetics of tacrolimus after sublingual administration is not characterized in paediatric liver transplant patients. Therefore, we aimed to develop a population pharmacokinetic model of sublingually administered tacrolimus in patients who cannot swallow the capsules due to their age, sedation status and/or mechanical ventilation during the first weeks post-transplantation.

Demographic, clinical and pharmacological variables, including tacrolimus whole blood concentrations obtained from therapeutic drug monitoring and data from dense-sampling pharmacokinetic profiles, were recorded in 26 paediatric patients with biliary atresia who underwent liver transplantation between 2016 and 2021. Population pharmacokinetic analysis was performed with NONMEM v7.4.

Disposition of tacrolimus was best characterized by a 2-compartment model with clearance achieving half of the maximum elimination capacity (CL

=4.1L/h) at 4.6days post-transplantation (T

). Compared to sedated patients, nonsedated status showed an increased first-order absorption rate constant (1.