Ovarian cancer is a medical term that includes a number of tumors with different molecular biology, phenotypes, tumor progression, etiology, and even different diagnosis. Some specific treatments are required to address this heterogeneity of ovarian cancer, thus molecular characterization may provide an important tool for this purpose. On a molecular level, proviral-integration site for Moloney-murine leukemia virus (PIM) kinases are over expressed in ovarian cancer and play a vital role in the regulation of different proteins responsible for this tumorigenesis. Likewise, the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway is also a central regulator of the ovarian cancer. Interestingly, recent research has linked the PIM kinases to the PI3K/AKT/mTOR pathway in several types of cancers, but their connection in ovarian cancer has not been studied yet. Once the exact relationship of PIM kinases with the PI3K/AKT/mTOR pathway is acquired in ovarian cancer, it will hopefully provide effective treatments on a molecular level. This review mainly focuses on the role of PIM kinases in ovarian cancer and their interactions with proteins involved in its progression. In addition, this review suggests a connection between the PIM kinases and the PI3K/AKT/mTOR pathway and their parallel mechanism in the regulation of ovarian cancer.
A multichannel three-dimensional chip of a microfluidic cell culture which enables the simulation of organs is called an “organ on a chip” (OC). With the integration of many other technologies, OCs have been mimicking organs, substituting animal models, and diminishing the time and cost of experiments which is better than the preceding conventional in vitro models, which make them imperative tools for finding functional properties, pathological states, and developmental studies of organs. In this review, recent progress regarding microfluidic devices and their applications in cell cultures is discussed to explain the advantages and limitations of these systems. Microfluidics is not a solution but only an approach to create a controlled environment, however, other supporting technologies are needed, depending upon what is intended to be achieved. Microfluidic platforms can be integrated with additional technologies to enhance the organ on chip simulations. Besides, new directions and areas are mentioned for interested researchers in this field, and future challenges regarding the simulation of OCs are also discussed, which will make microfluidics more accurate and beneficial for biological applications.
8 October 2018 in Cellular and Molecular Bioengineering
This study investigates the infinite-horizon optimal control (IHOC) problem for switched Boolean control networks with an average cost criterion. A primary challenge of this problem is the prohibitively high computational cost when dealing with large-scale networks. We attempt to develop a more efficient approach from a novel graph-theoretical perspective. First, a weighted directed graph structure called the optimal state transition graph (OSTG) is established, whose edges encode the optimal action for each admissible state transition between states reachable from a given initial state subject to various constraints. Then, we reduce the IHOC problem into a minimum-mean cycle (MMC) problem in the OSTG. Finally, we develop an algorithm that can quickly find a particular MMC by resorting to Karp's algorithm in the graph theory and construct an optimal switching control law based on state feedback. The time complexity analysis shows that our algorithm, albeit still running in exponential time, can outperform all the existing methods in terms of time efficiency. A 16-state-3-input signaling network in leukemia is used as a benchmark to test its effectiveness. Results show that the proposed graph-theoretical approach is much more computationally efficient and can reduce the running time dramatically: it runs hundreds or even thousands of times faster than the existing methods. The Python implementation of the algorithm is available at https://github.com/ShuhuaGao/sbcn_mmc.
In vivo studies have demonstrated that reasonable exercise training can improve endothelial function. To confirm the key role of wall shear stress induced by exercise on endothelial cells, and to understand how wall shear stress affects the structure and the function of endothelial cells, it is crucial to design and fabricate an in vitro multi-component parallel-plate flow chamber system which can closely replicate exercise-induced wall shear stress waveforms in artery. The in vivo wall shear stress waveforms from the common carotid artery of a healthy volunteer in resting and immediately after 30 min acute aerobic cycling exercise were first calculated by measuring the inner diameter and the center-line blood flow velocity with a color Doppler ultrasound. According to the above in vivo wall shear stress waveforms, we designed and fabricated a parallel-plate flow chamber system with appropriate components based on a lumped parameter hemodynamics model. To validate the feasibility of this system, human umbilical vein endothelial cells (HUVECs) line were cultured within the parallel-plate flow chamber under abovementioned two types of wall shear stress waveforms and the intracellular actin microfilaments and nitric oxide (NO) production level were evaluated using fluorescence microscope. Our results show that the trends of resting and exercise-induced wall shear stress waveforms, especially the maximal, minimal and mean wall shear stress as well as oscillatory shear index, generated by the parallel-plate flow chamber system are similar to those acquired from the common carotid artery. In addition, the cellular experiments demonstrate that the actin microfilaments and the production of NO within cells exposed to the two different wall shear stress waveforms exhibit different dynamic behaviors; there are larger numbers of actin microfilaments and higher level NO in cells exposed in exercise-induced wall shear stress condition than resting wall shear stress condition. The parallel-plate flow chamber system can well reproduce wall shear stress waveforms acquired from the common carotid artery in resting and immediately after exercise states. Furthermore, it can be used for studying the endothelial cells responses under resting and exercise-induced wall shear stress environments in vitro.
Sweat collection and real time monitoring of sweat rate play essential roles in physiology monitoring and assessment of an athlete’s performance during exercise. In this paper, we report a micropump for sweat simulant collection based on the capillary–evaporation effect. An electrochemical sensor is integrated into the micropump, which monitors the flow rate in real-time by detecting the current using three electrodes. The evaporation rate from micropore array, equivalent to the sweat rate, was theoretically and numerically investigated. The designed micropump yields the maximum collection rate as high as 0.235 L/min. In addition, the collection capability of the micropump was validated experimentally; the flow rate through the microchannel was further detected in real-time with the electrochemical sensor. The experimental maximum collection rate showed good consistency with the theoretical data. Our proposed device shows the potential for sweat collection and real-time monitoring of sweat rate, which is a promising candidate for being a wearable platform for real-time physiology and performance monitoring during exercise.