Intracellular signaling cascades following light irradiation

Low‐level light therapy (LLLT) using red to near‐infrared (NIR) (630–1000 nm) light has gained attention in recent years as a therapy in ophthalmology, neurology, dermatology, dentology, and regenerative medicine. Advancement in the basic science fields of photobiology has propelled LLLT into the therapeutic revolution. The potential mechanisms on LLLT‐induced biological effects have been investigated by numerous researchers throughout the world. This article reviews the current intracellular signaling cascades in photobiology and photomedicine under the influence of red to NIR light on mammalian cells. Specifically, mitochondrial retrograde signaling initiated by cytochrome c oxidase photomodulation is discussed in detail in the treatment of indications using LLLT, such as vitiligo management, retinal protection, and tumor therapy. The pathways through activating receptor tyrosine kinases are also highlighted in LLLT‐induced neuroprotection, wound healing, and skeletal muscle regeneration. The understanding of the LLLT‐induced biological reactions in cellular and subcellular levels is crucial for the advancement of LLLT in treatment of diseases.     

A Variant of Multi-task n-vehicle Exploration Problem: Maximizing Every Processor’s Average Profit

We discuss a variant of the multi-task n-vehicle exploration problem. Instead of requiring an optimal permutation of vehicles in every group, the new problem requires all vehicles in a group to arrive at the same destination. Given n tasks with assigned consume-time and profit, it may also be viewed as a maximization of every processor’s average profit. Further, we propose a new kind of partition problem in fractional form and analyze its computational complexity. By regarding fractional partition as a special case, we prove that the average profit maximization problem is NP-hard when the number of processors is fixed and it is strongly NP- hard in general. At last, a pseudo-polynomial time algorithm for the average profit maximization problem and the fractional partition problem is presented, using the idea of the pseudo-polynomial time algorithm for the classical partition problem.     

The Mitochondria-Independent Cytotoxic Effect of Leflunomide on RPMI-8226 Multiple Myeloma Cell Line

Leflunomide, an anti-inflammatory agent, has been shown to be effective in multiple myeloma (MM) treatment; however, the mechanism of this phenomenon has not been fully elucidated. The aim of the study was to assess the role of mitochondria and dihydroorotate dehydrogenase (DHODH) inhibition in the cytotoxicity of leflunomide in relation to the MM cell line RPMI 8226. The cytotoxic effect of teriflunomide—an active metabolite of leflunomide—was determined using MTT assay, apoptosis detection, and cell cycle analysis. To evaluate DHODH-dependent toxicity, the cultures treated with teriflunomide were supplemented with uridine. Additionally, the level of cellular thiols as oxidative stress symptom was measured as well as mitochondrial membrane potential and protein tyrosine kinases (PTK) activity. The localization of the compound in cell compartments was examined using HPLC method. Teriflunomide cytotoxicity was not abolished in uridine presence. Observed apoptosis occurred in a mitochondria-independent manner, there was also no decrease in cellular thiols level. Teriflunomide arrested cell cycle in the G2/M phase which is not typical for DHODH deficiency. PTK activity was decreased only at the highest drug concentration. Interestingly, teriflunomide was not detected in the mitochondria. The aforementioned results indicate DHODH- and mitochondria-independent mechanism of leflunomide toxicity against RPMI 8226 cell line.     

Theragnostic Applications of Mammal and Plant-Derived Extracellular Vesicles: Latest Findings,Current Technologies,and Prospects

The way cells communicate is not fully understood. However, it is well-known that extracellular vesicles (EVs) are involved. Researchers initially thought that EVs were used by cells to remove cellular waste. It is now clear that EVs function as signaling molecules released by cells to communicate with one another, carrying a cargo representing the mother cell. Furthermore, these EVs can be found in all biological fluids, making them the perfect non-invasive diagnostic tool, as their cargo causes functional changes in the cells upon receiving, unlike synthetic drug carriers. EVs last longer in circulation and instigate minor immune responses, making them the perfect drug carrier. This review sheds light on the latest development in EVs isolation, characterization and, application as therapeutic cargo, novel drug loading techniques, and diagnostic tools. We also address the advancement in plant-derived EVs, their characteristics, and applications; since plant-derived EVs only recently gained focus, we listed the latest findings. Although there is much more to learn about, EV is a wide field of research; what scientists have discovered so far is fascinating. This paper is suitable for those new to the field seeking to understand EVs and those already familiar with it but wanting to review the latest findings.     

基于多带复数小波与最大后验概率估计法的图像去噪方法

提出一种基于多带复数小波与最大后验概率估计方法的图像去噪方法，与二带小波以及相应的去噪方法相比，性能具有明显改善。     

An Extracellular Matrix‐Mimicking Hydrogel for Full Thickness Wound Healing in Diabetic Mice

An extracellular matrix‐mimicking hydrogel is developed consisting of a hyaluronan‐derived component with anti‐inflammatory activity, and a gelatin‐derived component offering adhesion sites for cell anchorage. The in situ‐forming hyaluronan‐gelatin (HA‐GEL) hydrogel displays a sponge‐like microporous morphology. Also, HA‐GEL shows a rapid swelling pattern reaching maximum weight swelling ratio within 10 min, while at the equilibrium state, fully swollen hydrogels display an exceedingly high water content with ≈2000% of the dry gel weight. Under typical 2D cell culture conditions, murine 3T3 fibroblasts adhere to, and proliferate on top of the HA‐GEL substrates, which demonstrate that HA‐GEL provides a favorable microenvironment for cell survival, adhesion, and proliferation. In vivo healing study further demonstrates HA‐GEL as a viable and effective treatment option to improve the healing outcome of full thickness wounds in diabetic mice by effectively depleting the inflammatory chemokine monocyte chemoattractant protein‐1 in the wound bed.     

Sulfation Patterns of Saccharides and Heavy Metal Ion Binding

Sulfated saccharides are an essential part of extracellular matrices, and they are involved in a large number of interactions. Sulfated saccharide matrices in organisms accumulate heavy metal ions in addition to other essential metal ions. Accumulation of heavy metal ions alters the function of the organisms and cells, resulting in severe and irreversible damage. The effect of the sulfation pattern of saccharides on heavy metal binding preferences is enigmatic because the accessibility to structurally defined sulfated saccharides is limited and because standard analytical techniques cannot be used to quantify these interactions. We developed a new strategy that combines enzymatic and chemical synthesis with surface chemistry and label-free electrochemical sensing to study the interactions between well-defined sulfated saccharides and heavy metal ions. By using these tools we showed that the sulfation pattern of hyaluronic acid governs their heavy metal ions binding preferences.     

Mathematical modeling for multisite phosphorylation with scaffold binding in cell signaling

The mating decision in budding yeast is a switch‐like or bistability response that allows cells to filter out weak pheromone signals or avoid improper mating when a mate is sufficiently close. However, the molecular mechanisms that control the bistability decision are not yet fully understood. In many cases, scaffold proteins are thought to play a key role during this process. A workable definition of a scaffold is a protein that dynamically binds to two or more consecutively acting components of a signaling cascade, such as protein kinase and that kinase's substrate. Here, we show that bistability mechanism can arise from multisite phosphorylation system with scaffold binding when phosphorylation and dephosphorylation occur at different locations. This scaffold binding in a multisite phosphorylation system can robustly result in multiple steady states. By developing generic mathematical models, we argue that the scaffold protein plays an important role in creating bistability, and by treating parameters symbolically, we also thereby reduce the complexity of calculating steady states from simulating differential equations to finding the roots of polynomials, of which the degree depends on the number of phosphorylation sites N. Copyright © 2013 John Wiley & Sons, Ltd.