Melatonin as a regulator of apoptosis in leukaemia: molecular mechanism and therapeutic perspectives.

Leukaemia is a dangerous malignancy that causes thousands of deaths every year throughout the world. The rate of morbidity and mortality is significant despite many advancements in therapy strategies for affected individuals. Most antitumour medications used now in clinical oncology use apoptotic signalling pathways to induce cancer cell death. Accumulated data have shown a direct correlation between inducing apoptosis in cancer cells with higher tumour regression and survival. Until now, the efficacy of melatonin as a powerful antitumour agent has been firmly established. A change in melatonin concentrations has been reported in multiple tumours such as endometrial, hematopoietic, and breast cancers. Findings show that melatonin's anticancer properties, such as its prooxidation function and ability to promote apoptosis, indicate the possibility of utilizing this natural substance as a promising agent in innovative cancer therapy approaches. Melatonin stimulates cell apoptosis via the regulation of many apoptosis facilitators, including mitochondria, cytochrome c, Bcl-2, production of reactive oxygen species, and apoptosis receptors. This paper aimed to further assess the anticancer effects of melatonin through the apoptotic pathway, considering the role that cellular apoptosis plays in the pathogenesis of cancer. The effect of melatonin may mean that it is appropriate for use as an adjuvant, along with other therapeutic approaches such as radiotherapy and chemotherapy.

A spotlight on the interplay between Wnt/ß-catenin signaling and circular RNAs in hepatocellular carcinoma progression.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers due to multifocal development and distant metastasis resulting from late diagnosis. Consequently, new approaches to HCC diagnosis and treatment are required to reduce mortality rates. A large body of evidence suggests that non-coding RNAs (ncRNAs) are important in cancer initiation and progression. Cancer cells release many of these ncRNAs into the blood or urine, enabling their use as a diagnostic tool. Circular RNAs (CircRNAs) are as a members of the ncRNAs that regulate cancer cell expansion, migration, metastasis, and chemoresistance through different mechanisms such as the Wnt/ß-catenin Signaling pathway. The Wnt/ß-catenin pathway plays prominent roles in several biological processes including organogenesis, stem cell regeneration, and cell survival. Aberrant signaling of both pathways mentioned above could affect the progression and metastasis of many cancers, including HCC. Based on several studies investigated in the current review, circRNAs have an effect on HCC formation and progression by sponging miRNAs and RNA-binding proteins (RBPs) and regulating the Wnt/ß-catenin signaling pathway. Therefore, circRNAs/miRNAs or RBPs/Wnt/ß-catenin signaling pathway could be considered promising prognostic and therapeutic targets in HCC.

Accelerated Diffusion-Weighted MRI of Rectal Cancer Using a Residual Convolutional Network.

This work presents a deep-learning-based denoising technique to accelerate the acquisition of high b-value diffusion-weighted MRI for rectal cancer. A denoising convolutional neural network (DCNN) with a combined L1-L2 loss function was developed to denoise high b-value diffusion-weighted MRI data acquired with fewer repetitions (NEX: number of excitations) using the low b-value image as an anatomical guide. DCNN was trained using 85 datasets acquired on patients with rectal cancer and tested on 20 different datasets with NEX = 1, 2, and 4, corresponding to acceleration factors of 16, 8, and 4, respectively. Image quality was assessed qualitatively by expert body radiologists. Reader 1 scored similar overall image quality between denoised images with NEX = 1 and NEX = 2, which were slightly lower than the reference. Reader 2 scored similar quality between NEX = 1 and the reference, while better quality for NEX = 2. Denoised images with fourfold acceleration (NEX = 4) received even higher scores than the reference, which is due in part to the effect of gas-related motion in the rectum, which affects longer acquisitions. The proposed deep learning denoising technique can enable eightfold acceleration with similar image quality (average image quality = 2.8 ± 0.5) and fourfold acceleration with higher image quality (3.0 ± 0.6) than the clinical standard (2.5 ± 0.8) for improved diagnosis of rectal cancer.

Mesenchymal Stem Cell-Derived Antimicrobial Peptides as Potential Anti-Neoplastic Agents: New Insight into Anticancer Mechanisms of Stem Cells and Exosomes.

Mesenchymal stem cells (MSCs), as adult multipotent cells, possess considerable regenerative and anti-neoplastic effects, from inducing apoptosis in the cancer cells to reducing multidrug resistance that bring them up as an appropriate alternative for cancer treatment. These cells can alter the behavior of cancer cells, the condition of the tumor microenvironment, and the activity of immune cells that result in tumor regression. It has been observed that during inflammatory conditions, a well-known feature of the tumor microenvironment, the MSCs produce and release some molecules called "antimicrobial peptides (AMPs)" with demonstrated anti-neoplastic effects. These peptides have remarkable targeted anticancer effects by attaching to the negatively charged membrane of neoplastic cells, disrupting the membrane, and interfering with intracellular pathways. Therefore, AMPs could be considered as a part of the wide-ranging anti-neoplastic effects of MSCs. This review focuses on the possible anti-neoplastic effects of MSCs-derived AMPs and their mechanisms. It also discusses preconditioning approaches and using exosomes to enhance AMP production and delivery from MSCs to cancer cells. Besides, the clinical administration of MSCs-derived AMPs, along with their challenges in clinical practice, were debated.

Nuclear magnetic resonance spin-lattice relaxation of lithium ions in aqueous solution by NMR and molecular dynamics.

We study the aqueous solvation dynamics of lithium ions using nuclear magnetic resonance spectroscopy, molecular dynamics, and viscosity measurements. Several relaxation mechanisms are examined to explain the strong increases of spin-lattice relaxation toward high concentrations. The use of both 6Li and 7Li isotopes is helpful to identify the quadrupolar contribution to the relaxation rate. In particular, it is found that the quadrupolar interaction constitutes the strongest contribution above a concentration of ∼10 molal. The next-strongest contribution arises from interactions that scale with the square of the gyromagnetic ratio (mostly the dipolar interaction), and the experimental relaxation rates appear to be fully accounted for when these mechanisms are combined over the concentration range up to the saturation concentration. The study of solvation dynamics, particularly at high concentrations, could be of relevance for electrolyte dynamics in aqueous Li-ion rechargeable batteries.

Mapping oscillating magnetic fields around rechargeable batteries.

Power storage devices such as batteries are a crucial part of modern technology. The development and use of batteries has accelerated in the past decades, yet there are only a few techniques that allow gathering vital information from battery cells in a nonivasive fashion. A widely used technique to investigate batteries is electrical impedance spectroscopy (EIS), which provides information on how the impedance of a cell changes as a function of the frequency of applied alternating currents. Building on recent developments of inside-out MRI (ioMRI), a technique is presented here which produces spatially-resolved maps of the oscillating magnetic fields originating from the alternating electrical currents distributed within a cell. The technique works by using an MRI pulse sequence synchronized with a gated alternating current applied to the cell terminals. The approach is benchmarked with a current-carrying wire coil, and demonstrated with commercial and prototype lithium-ion cells. Marked changes in the fields are observed for different cell types.

Nuclear magnetic resonance spectroscopy of rechargeable pouch cell batteries: beating the skin depth by excitation and detection via the casing.

Rechargeable batteries are notoriously difficult to examine nondestructively, and the obscurity of many failure modes provides a strong motivation for developing efficient and detailed diagnostic techniques that can provide information during realistic operating conditions. In-situ NMR spectroscopy has become a powerful technique for the study of electrochemical processes, but has mostly been limited to laboratory cells. One significant challenge to applying this method to commercial cells has been that the radiofrequency, required for NMR excitation and detection, cannot easily penetrate the battery casing due to the skin depth. This complication has limited such studies to special research cell designs or to 'inside-out' measurement approaches. This article demonstrates that it is possible to use the battery cell as a resonator in a tuned circuit, thereby allowing signals to be excited inside the cell, and for them to subsequently be detected via the resonant circuit. Employing this approach, 7Li NMR signals from the electrolyte, as well as from intercalated and plated metallic lithium in a multilayer (rolled) commercial pouch cell battery were obtained. Therefore, it is anticipated that critical nondestructive device characterization can be performed with this technique in realistic and even commercial cell designs.

Sensitive magnetometry reveals inhomogeneities in charge storage and weak transient internal currents in Li-ion cells.

The ever-increasing demand for high-capacity rechargeable batteries highlights the need for sensitive and accurate diagnostic technology for determining the state of a cell, for identifying and localizing defects, and for sensing capacity loss mechanisms. Here, we leverage atomic magnetometry to map the weak induced magnetic fields around Li-ion battery cells in a magnetically shielded environment. The ability to rapidly measure cells nondestructively allows testing even commercial cells in their actual operating conditions, as a function of state of charge. These measurements provide maps of the magnetic susceptibility of the cell, which follow trends characteristic for the battery materials under study upon discharge. In particular, hot spots of charge storage are identified. In addition, the measurements reveal the capability to measure transient internal current effects, at a level of µA, which are shown to be dependent upon the state of charge. These effects highlight noncontact battery characterization opportunities. The diagnostic power of this technique could be used for the assessment of cells in research, quality control, or during operation, and could help uncover details of charge storage and failure processes in cells.

In situ and operando magnetic resonance imaging of electrochemical cells: A perspective.

Nuclear Magnetic Resonance (NMR) spectroscopy and Magnetic Resonance Imaging (MRI) of electrochemical devices have become powerful tools for the in situ investigation of electrochemical processes. The techniques often take advantage of NMR's nondestructive/noninvasive properties, its sensitivity to frequency shifts, internal interactions, and transport processes, as well as its ability to measure liquid phases and disordered materials. Here, we provide a perspective on recent work on in situ MRI of electrochemical devices, batteries and relevant model systems, and discuss their applications and promises in assessing device performance, and electrochemical processes in cells.

Diagnosing current distributions in batteries with magnetic resonance imaging.

Batteries and their defects are notoriously difficult to analyze non-destructively, and consequently, many defects and failures remain little noticed and characterized until they cause grave damage. The measurement of the current density distributions inside a battery could reveal information about deviations from ideal cell behavior, and could thus provide early signs of deterioration or failures. Here, we describe methodology for fast nondestructive assessment and visualization of the effects of current distributions inside Li-ion pouch cells. The technique, based on magnetic resonance imaging (MRI), allows measuring magnetic field maps during charging/discharging. Marked changes in the distributions are observed as a function of the state of charge, and also upon sustaining damage. In particular, it is shown that nonlinearities and asymmetries of current distributions could be mapped at different charge states. Furthermore, hotspots of current flow are also shown to correlate with hotspots in charge storage. This technique could potentially be of great utility in diagnosing the health of cells and their behavior under different charging or environmental conditions.

Rechargeable lithium-ion cell state of charge and defect detection by in-situ inside-out magnetic resonance imaging.

When and why does a rechargeable battery lose capacity or go bad? This is a question that is surprisingly difficult to answer; yet, it lies at the heart of progress in the fields of consumer electronics, electric vehicles, and electrical storage. The difficulty is related to the limited amount of information one can obtain from a cell without taking it apart and analyzing it destructively. Here, we demonstrate that the measurement of tiny induced magnetic field changes within a cell can be used to assess the level of lithium incorporation into the electrode materials, and diagnose certain cell flaws that could arise from assembly. The measurements are fast, can be performed on finished and unfinished cells, and most importantly, can be done nondestructively with cells that are compatible with commercial design requirements with conductive enclosures.

Real-time 3D imaging of microstructure growth in battery cells using indirect MRI.

Lithium metal is a promising anode material for Li-ion batteries due to its high theoretical specific capacity and low potential. The growth of dendrites is a major barrier to the development of high capacity, rechargeable Li batteries with lithium metal anodes, and hence, significant efforts have been undertaken to develop new electrolytes and separator materials that can prevent this process or promote smooth deposits at the anode. Central to these goals, and to the task of understanding the conditions that initiate and propagate dendrite growth, is the development of analytical and nondestructive techniques that can be applied in situ to functioning batteries. MRI has recently been demonstrated to provide noninvasive imaging methodology that can detect and localize microstructure buildup. However, until now, monitoring dendrite growth by MRI has been limited to observing the relatively insensitive metal nucleus directly, thus restricting the temporal and spatial resolution and requiring special hardware and acquisition modes. Here, we present an alternative approach to detect a broad class of metallic dendrite growth via the dendrites' indirect effects on the surrounding electrolyte, allowing for the application of fast 3D (1)H MRI experiments with high resolution. We use these experiments to reconstruct 3D images of growing Li dendrites from MRI, revealing details about the growth rate and fractal behavior. Radiofrequency and static magnetic field calculations are used alongside the images to quantify the amount of the growing structures.

Correlating Microstructural Lithium Metal Growth with Electrolyte Salt Depletion in Lithium Batteries Using 7Li MRI.

Lithium dendrite growth in lithium ion and lithium rechargeable batteries is associated with severe safety concerns. To overcome these problems, a fundamental understanding of the growth mechanism of dendrites under working conditions is needed. In this work, in situ (7)Li magnetic resonance (MRI) is performed on both the electrolyte and lithium metal electrodes in symmetric lithium cells, allowing the behavior of the electrolyte concentration gradient to be studied and correlated with the type and rate of microstructure growth on the Li metal electrode. For this purpose, chemical shift (CS) imaging of the metal electrodes is a particularly sensitive diagnostic method, enabling a clear distinction to be made between different types of microstructural growth occurring at the electrode surface and the eventual dendrite growth between the electrodes. The CS imaging shows that mossy types of microstructure grow close to the surface of the anode from the beginning of charge in every cell studied, while dendritic growth is triggered much later. Simple metrics have been developed to interpret the MRI data sets and to compare results from a series of cells charged at different current densities. The results show that at high charge rates, there is a strong correlation between the onset time of dendrite growth and the local depletion of the electrolyte at the surface of the electrode observed both experimentally and predicted theoretical (via the Sand's time model). A separate mechanism of dendrite growth is observed at low currents, which is not governed by salt depletion in the bulk liquid electrolyte. The MRI approach presented here allows the rate and nature of a process that occurs in the solid electrode to be correlated with the concentrations of components in the electrolyte.