Haneycrawford0321

In vitro experiments revealed that overexpression of mir-26a decreased significantly ULK1, mRNA, and protein expression. Contrariwise, the Tt recovered ULK1 expression by mir-26a decrease. Due to triple therapy repressed mir-26a expression, we hypothesized this drug combination could be involved in mir-26a transcription regulation. Consequently, we analyzed the mir-26a promoter sequence and found two HIF-1α transcription factor recognition sites. We developed two different HIF-1α stabilization models. Both showed mir-26a overexpression and ULK1 reduction in hypoxic conditions. Immunoprecipitation experiments were performed and HIF-1α enrichment was observed in mir-26a promoter. Surprisingly, Tt diminished HIF-1α detection and restored ULK1 mRNA expression. These results reveal an important regulation mechanism controlled by the signaling that activates HIF-1α and that in turn regulates mir-26a transcription.

This study aimed to compare the long-term outcomes of liver transplantation (LT) and liver resection (LR) among patients with stage I and II hepatocellular carcinoma (HCC).

SEER 18 registry from 2004 to 2015 was retrieved for this study. We included 1,765 and 1,746 cases with stage I-II (AJCC, 7

) HCC in the multivariable analyses and instrumental variable (IV) analyses, respectively. Propensity score matching (PSM) was further carried out to ensure comparability. Propensity score to receive LT was adjusted by stabilized inverse probability of treatment weighting (IPTW) and standardized mortality ratio weighting (SMRW) methods. In addition, IV analysis was performed to adjust both measured and unmeasured confounding factors.

We identified 1,000 (56.7%) and 765 (43.3%) patients treated with LR and LT, respectively. In the multivariable adjusted cohort, after adjusting potential confounders, patients undergoing LT offered significant prognostic advantages over LR in overall survival (OS, P < 0.001) ante was to increase in the future, average long-term survival may also increase. However, for some special populations such as the elderly patients, owing to the similar outcomes between LT and LR, the selection of LT should be cautious.

LT provided a survival benefit for cases with stage I-II HCC. These results indicated that if LT rate was to increase in the future, average long-term survival may also increase. However, for some special populations such as the elderly patients, owing to the similar outcomes between LT and LR, the selection of LT should be cautious.

To evaluate fitting quality and repeatability of four mathematical models for diffusion weighted imaging (DWI) during tumor progression in mouse xenograft model of prostate cancer.

Human prostate cancer cells (PC-3) were implanted subcutaneously in right hind limbs of 11 immunodeficient mice. Tumor growth was followed by weekly DWI examinations using a 7T MR scanner. Additional DWI examination was performed after repositioning following the fourth DWI examination to evaluate short term repeatability. DWI was performed using 15 and 12 b-values in the ranges of 0-500 and 0-2000 s/mm

, respectively. Corrected Akaike information criteria and F-ratio were used to evaluate fitting quality of each model (mono-exponential, stretched exponential, kurtosis, and bi-exponential).

Significant changes were observed in DWI data during the tumor growth, indicated by ADC

, ADC

, and ADC

. Similar results were obtained using low as well as high b-values. No marked changes in model preference were present between the weeks 1-4. R406 mw The parameters of the mono-exponential, stretched exponential, and kurtosis models had smaller confidence interval and coefficient of repeatability values than the parameters of the bi-exponential model.

Stretched exponential and kurtosis models showed better fit to DWI data than the mono-exponential model and presented with good repeatability.

Stretched exponential and kurtosis models showed better fit to DWI data than the mono-exponential model and presented with good repeatability.Drug repositioning is a promising and powerful innovative strategy in the field of drug discovery. In this study, we screened a compound-library containing 800 Food and Drug Administration approved drugs for their anti-leukemic effect. All screening activities made use of human peripheral blood mononuclear cells (PBMCs), isolated from healthy or leukemic donors. Compounds with confirmed cytotoxicity were selected and classified in three groups i) anti-neoplastic compounds which are drugs used in leukemia treatment, ii) compounds known to have an anti-cancer effect and iii) compounds demonstrating an anti-leukemic potential for the first time. The latter group was the most interesting from a drug repositioning perspective and yielded a single compound, namely Isoprenaline which is a non-selective β-adrenergic agonist. Analysis of the cytotoxic effect of this drug indicated that it induces sustainable intracellular ATP depletion leading, over time, to necrotic cell death. We exploited the Isoprenaline-induced intracellular ATP depletion to sensitize primary leukemic cells to fludarabine (purine analogue) and Ibrutinib (Bruton's tyrosine kinase inhibitor) treatment. In-vitro treatment of primary leukemic cells with a combination of Isoprenaline/fludarabine or Isoprenaline/Ibrutinib showed a very high synergistic effect. These combinations could constitute a new efficient regimen for CLL treatment following successful evaluation in animal models and clinical trials.In late 2019 and early 2020, the world witnessed the outbreak of the SARS-CoV-2 (also referred as COVID-19) in Wuhan, China. Its rapid expansion worldwide and its contagiousness rate have forced the activation of several measures to contain the pandemic, mostly through confinement and identification of infected patients and potential contacts by testing.Immune checkpoint inhibitor therapy has revolutionized the field of cancer immunotherapy. Even though it has shown a durable response in some solid tumors, several patients do not respond to these agents, irrespective of predictive biomarker (PD-L1, MSI, TMB) status. Multiple preclinical, as well as early-phase clinical studies are ongoing for combining immune checkpoint inhibitors with anti-cancer and/or non-anti-cancer drugs for beneficial therapeutic interactions. In this review, we discuss the mechanistic basis behind the combination of immune checkpoint inhibitors with other drugs currently being studied in early phase clinical studies including conventional chemotherapy drugs, metronomic chemotherapy, thalidomide and its derivatives, epigenetic therapy, targeted therapy, inhibitors of DNA damage repair, other small molecule inhibitors, anti-tumor antibodies hormonal therapy, multiple checkpoint Inhibitors, microbiome therapeutics, oncolytic viruses, radiotherapy, drugs targeting myeloid-derived suppressor cells, drugs targeting Tregs, drugs targeting renin-angiotensin system, drugs targeting the autonomic nervous system, metformin, etc. We also highlight how translational research strategies can help better understand the true therapeutic potential of such combinations.

This study was conducted to compare the microleakage and characteristics of the resin-tooth tissue interface between self-etch and etch-and-rinse adhesive systems after 48 hours and 3 months.

40 extracted premolar teeth were randomly divided into 2 groups 1-step self-etch adhesive system - Optibond™ All-In-One, and 2-step etch-and-rinse adhesive system - Adper™ Single Bond 2. Both groups were subjected to 500 thermocycles (5°C-55°C) before scanning electron microscope (SEM) analysis or microleakage trial at 48-hour and 3-month time periods.

SEM images showed the hybrid layer thickness, diameter, and length of resin tags of the self-etch adhesive (0.42 ± 0.14 µm; 1.49 ± 0.45 µm; 16.35 ± 14.26 µm) were smaller than those of the etch-and-rinse adhesive (4.39 ± 1.52 µm; 3.49 ± 1 µm; 52.81 ± 35.81 µm). In dentin, the microleakage scores of the 2 adhesives were not different in both time periods (48 hours/3 months). However, the microleakage score of etch-and-rinse adhesive increased significantly after 3 months (0.8 ± 0.63 and 1.9 ± 0.88,

< 0.05).

The self-etch adhesive exhibited better long-term sealing ability in dentin when compared to that of the etch-and-rinse adhesive. The greater hybrid layer thickness and dimensions of resin tags did not guarantee reliable, long-lasting sealing in the bonding area.

The self-etch adhesive exhibited better long-term sealing ability in dentin when compared to that of the etch-and-rinse adhesive. The greater hybrid layer thickness and dimensions of resin tags did not guarantee reliable, long-lasting sealing in the bonding area.

This study was conducted to compare the post-fracture survival rate of endodontically treated molar endodontically treated teeth (molar ETT) restored with resin composites or crowns and to identify potential risk factors, using a retrospective cohort design.

Dental records of molar ETT with crowns or composite restorations (recall period, 2015-2019) were collected based on inclusion and exclusion criteria. The incidence of unrestorable fractures was identified, and molar ETT were classified according to survival. Information on potential risk factors was collected. Survival rates and potential risk factors were analyzed using the Kaplan-Meier log-rank test and Cox regression model.

The overall survival rate of molar ETT was 87% (mean recall period, 31.73 ± 17.56 months). The survival rates of molar ETT restored with composites and crowns were 81.6% and 92.7%, reflecting a significant difference (

< 0.05). However, ETT restored with composites showed a 100% survival rate if only 1 surface was lost, which was comparable to the survival rate of ETT with crowns. The survival rates of ETT with composites and crowns were significantly different (97.6% vs. 83.7%) in the short-term (12-24 months), but not in the long-term (> 24 months) (87.8% vs. 79.5%).

The survival rate from fracture was higher for molar ETT restored with crowns was higher than for ETT restored with composites, especially in the first 2 years after restoration. Molar ETT with limited tooth structure loss only on the occlusal surface could be successfully restored with composite restorations.

The survival rate from fracture was higher for molar ETT restored with crowns was higher than for ETT restored with composites, especially in the first 2 years after restoration. Molar ETT with limited tooth structure loss only on the occlusal surface could be successfully restored with composite restorations.

This study evaluated the effect of repeated uses and autoclaving in the instrumented area, fracture resistance, and time of instrumentation of thermally treated nickel-titanium reciprocating systems.

Two hundred simulated canals were instrumented using Reciproc Blue and WaveOne Gold. Each file was used up to 10 times or until fracture. The instrumented area was measured in pre- and post-operative images, using ImageJ software. Kaplan-Meier survival analysis evaluated the number of uses of instruments before fracture. Instrumented area and time of instrumentation were analyzed by Mann-Whitney U test and Kruskal-Wallis. Correlations among the number of uses and instrumented area were measured. The level of statistical significance was set at

< 0.05.

Reciproc Blue presented a higher estimated number of uses in comparison with WaveOne Gold (

= 0.026), but autoclaving did not affect the resistance to fracture of instruments (

> 0.05). The instrumented area was different among the evaluated groups (

= 0.