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Autophagy has been of novel interest since it was first demonstrated to have effect in Burkitt’s lymphoma. Since that time, the autophagy agents chloroquine and hydroxychloroquine have become the only FDA (Food and Drug Administration)-approved autophagy inhibitors. While not approved for cancer therapy, there are ongoing clinical trials to evaluate their safety and efficacy. Pevonedistat has emerged as a novel inhibitor through the neddylation pathway and is an autophagy activator. This paper summarizes and presents current clinical trials for hydroxychloroquine (HCQ), chloroquine (CQ), and Pevonedistat for the clinician.

Interest in combining metallic nanoparticles, such as iron (SPIONs), gold (AuNPs) and bismuth oxide (BiONPs), with radiotherapy has increased due to the promising therapeutic advantages. While the underlying physical mechanisms of NP-enhanced radiotherapy have been extensively explored, only a few research works were motivated to quantify its contribution in an experimental dosimetry setting. This work aims to explore the feasibility of radiochromic films to measure the physical dose enhancement (DE) caused by the release of secondary electrons and photons during NP–radiotherapy interactions. A 10 mM each of SPIONs, AuNPs or BiONPs was loaded into zipper bags packed with GAFCHROMIC™ EBT3 films. The samples were exposed to a single radiation dose of 4.0 Gy with clinically relevant beams. Scanning was conducted using a flatbed scanner in red-component analysis for optimum sensitivity. Experimental dose enhancement factors (DEFExperimental) were then calculated using the ratio of absorbed doses (with/without NPs) converted from the films’ calibration curves. DEFExperimental for all NPs showed no significant physical DE beyond the uncertainty limits (p > 0.05). These results suggest that SPIONs, AuNPs and BiONPs might potentially enhance the dose in these clinical beams. However, changes in NPs concentration, as well as dosimeter sensitivity, are important to produce observable impact.

Venous thromboembolism (VTE), which encompasses deep venous thrombosis (DVT) and pulmonary embolism (PE), is a major public health concern due to its high incidences of morbidity and mortality. Patients who have experienced trauma with prolonged immobilization are at an increased risk of developing VTE. Plasma D-dimer levels have been known to be elevated in trauma patients, and they were closely correlated with the number of fractures. In other words, plasma D-dimer levels cannot be used as the only indicator of VTE in trauma cases. Given the limitations, further study is needed to explore other potential biomarkers for diagnosing VTE. To date, various established and novel VTE biomarkers have been studied in terms of their potential for predicting VTE, diagnostic performance, and improving clinical therapy for VTE. Therefore, this review aims to provide information regarding classic and essential haemostasis (including prothrombin time (PT), activated partial thromboplastin time (aPTT), D-dimer, fibrinogen, thrombin generation, protein C, protein S, antithrombin, tissue factor pathway inhibitor, and platelet count) and inflammatory biomarkers (C-reactive protein, erythrocyte sedimentation rate, and soluble P-selectin) as potential diagnostic biomarkers that can predict the risk of VTE development among trauma patients with prolonged immobilization. Thus, further advancement in risk stratification using these biomarkers would allow for a better diagnosis of patients with VTE, especially in areas with limited resources.

Multiple myeloma (MM) is an exceptionally complicated and heterogeneous disease that is caused by the abnormal proliferation of malignant monoclonal plasma cells initiated in the bone marrow. In disease progression, a multistep process including differentiation, proliferation, and invasion is involved. Despite great improvement in treatment outcomes in recent years due to the substantial discovery of novel therapeutic drugs, MM is still regarded as an incurable disease. Patients with MM are afflicted by confronting remission periods accompanied by relapse or progression outcomes, which inevitably progress to the refractory stage. In this regard, MM may need new medications or modifications in therapeutic strategies to overcome resistance. A variety of genetic abnormalities (e.g., point mutations, translocations, and deletions) and epigenetic changes (e.g., DNA methylation, histone modification, and non-coding RNA) contribute to the pathogenesis and development of MM. Here, we review the significant roles of epigenetic mechanisms in the development and progression of MM. We also highlight epigenetic pathways as potential novel treatment avenues for MM, including their interplay, use of epigenetic inhibitors, and major involvement in immuno-oncology.

Introduction: Safranal, which endows saffron its unique aroma, causes vasodilatation and has a hypotensive effect in animal studies, but the mechanisms of these effects are unknown. In this study, we investigated the mechanisms of safranal vasodilation. Methods: Isolated rat endothelium-intact or -denuded aortic rings were precontracted with phenylephrine and then relaxed with safranal. To further assess the involvement of nitric oxide, prostaglandins, guanylate cyclase, and phospholipase A2 in safranal-induced vasodilation, aortic rings were preincubated with L-NAME, indomethacin, methylene blue, or quinacrine, respectively, then precontracted with phenylephrine, and safranal concentration–response curves were established. To explore the effects of safranal on Ca2+ influx, phenylephrine and CaCl2 concentration–response curves were established in the presence of safranal. Furthermore, the effect of safranal on aortic rings in the presence of ouabain, a Na+-K+ ATPase inhibitor, was studied to explore the contribution of Na+/Ca2+ exchanger to this vasodilation. Results: Safranal caused vasodilation in endothelium-intact and endothelium-denuded aortic rings. The vasodilation was not eliminated by pretreatment with L-NAME, indomethacin, methylene blue, or quinacrine, indicating the lack of a role for NO/cGMP. Safranal significantly inhibited the maximum contractions induced by phenylephrine, or by CaCl2 in Ca2+-free depolarizing buffer. Safranal also relaxed contractions induced by ouabain, but pretreatment with safranal totally abolished the development of ouabain contractions. Discussion/Conclusion: Inhibition of Na+-K+ ATPase by ouabain leads to the accumulation of Na+ intracellularly, forcing the Na+/Ca2+ exchanger to work in reverse mode, thus causing a contraction. Inhibition of the development of this contraction by preincubation with safranal indicates that safranal inhibited the Na+/Ca2+ exchanger. We conclude that safranal vasodilation is mediated by the inhibition of calcium influx from extracellular space through L-type Ca2+ channels and by the inhibition of the Na+/Ca2+ exchanger.

The objective of this study is to investigate the influence of veneering technique (hand-layering vs. milling) on the fracture resistance of bi-layer implant-supported zirconia-based hybrid-abutment crowns. Mandibular molar copings were anatomically designed and milled. Copings were then veneered by hand-layering (HL) (n = 20) and milling using the Cad-On technique (LD) (n = 20). Crowns were cemented to zirconia hybrid-abutments. Ten samples of each group acted as a control while the remaining ten samples were subjected to fatigue in a chewing simulator. Crowns were loaded between 50 and 100 N for 1.2 million cycles under simultaneous temperature fluctuation between 5 and 55 °C. Crowns were then subjected to static load a to fracture test. Data were statistically analysed using the one-way ANOVA. Randomly selected crowns from each group were observed under scanning electron microscopy to view fractured surfaces. Study results indicate that during fatigue, LD crowns had a 100% survival rate; while HL crowns had a 50% failure rate. Fracture resistance of LD crowns was statistically significantly higher than that of HL crowns at the baseline and after fatigue (p ≤ 0.05). However, fatigue did not cause a statistically significant reduction in fracture resistance in both LD and HL groups (p > 0.05). Copings fractured in the LD crowns only and the fracture path was different in both LD and HL groups. According to the results, it was concluded that milled veneer implant-supported hybrid-abutment crowns exhibit significantly higher fracture resistance, and better withstand clinical masticatory loads in the posterior region compared to the hand-layered technique. Also, fatigue application and artificial aging caused no significant strength reduction in both techniques. Clinical significance: Different veneering techniques and materials (hand-layering or milling) act differently to clinical forces and environment and may be prone to early chipping during service. Therefore, practitioners are urged to consider the appropriate veneering protocol for posterior implant-supported hybrid-abutment restorations.

In this paper the synthesis of self-organized Titania nanotubes (TNTs) by a facile potentiostatic anodization in a glycerol-based electrolyte is reported. The optimized TNTs were subsequently reduced through a cathodic reduction process to enhance its capacitive performance. FESEM and XRD were used to characterize the morphology and crystal structure of the synthesized samples. XPS analysis confirmed the reduction of Ti4+ to Ti3+ ions in the reduced Titania nanotubes (R-TNTs). The tube diameter and separation between the tubes were greatly influenced by the applied voltage. TNTs synthesized at voltage of 30 V for 60 min exhibited 86 nm and 1.1 µm of tube diameter and length, respectively and showed high specific capacitance of 0.33 mF cm−2 at current density of 0.02 mA cm−2. After reduction at 5 V for 30 s, the specific capacitance increased by about seven times (2.28 mF cm−2) at 0.5 mA cm−2 and recorded about 86% capacitance retention after 1000 continuous cycling at 0.2 mA cm−2, as compared to TNTs, retained about 61% at 0.01 mA cm−2. The charge transfer resistance drastically reduced from 6.2 Ω for TNTs to 0.55 Ω for R-TNTs, indicating an improvement in the transfer of electrons and ions across the electrode–electrolyte interface.