Embryonic Stem Cell Bioprinting for Uniform and Controlled Size Embryoid Body Formation

Embryonic stem cells ESCs are pluripotent with multilineage potential to differentiate into virtually all cell types in the organism and thus hold a great promise for cell therapy and regenerative medicine. In vitro differentiation of ESCs starts with a phase known as embryoid body EB formation. EB mimics the early stages of embryogenesis and plays an essential role in ESC differentiation in vitro. EB uniformity and size are critical parameters that directly influence the phenotype expression of ESCs. Various methods have been developed to form EBs, which involve natural aggregation of cells. However, challenges persist to form EBs with controlled size, shape, and uniformity in a reproducible manner. The current hanging-drop methods are labor intensive and time consuming. In this study, we report an approach to form controllable, uniform-sized EBs by integrating bioprinting technologies with the existing hanging-drop method. The approach presented here is simple, robust, and rapid. We present significantly enhanced EB size uniformity compared to the conventional manual hanging-drop method

Functional Maintenance of Differentiated Embryoid Bodies in Microfluidic Systems: A Platform for Personalized Medicine

Hormone replacement therapies have become important for treating diseases such as premature ovarian failure or menopausal complications. The clinical use of bioidentical hormones might significantly reduce some of the potential risks reportedly associated with the use of synthetic hormones. In the present study, we demonstrate the utility and advantage of a microfluidic chip culture system to enhance the development of personalized, on-demand, treatment modules using embryoid bodies (EBs). Functional EBs cultured on microfluidic chips represent a platform for personalized, patient-specific treatment cassettes that can be cryopreserved until required for treatment. We assessed the viability, differentiation, and functionality of EBs cultured and cryopreserved in this system. During extended microfluidic culture, estradiol, progesterone, testosterone, and anti-müllerian hormone levels were measured, and the expression of differentiated steroidogenic cells was confirmed by immunocytochemistry assay for the ovarian tissue markers anti-müllerian hormone receptor type II, follicle-stimulating hormone receptor, and inhibin β-A and the estrogen biosynthesis enzyme aromatase. Our studies showed that under microfluidic conditions, differentiated steroidogenic EBs continued to secrete estradiol and progesterone at physiologically relevant concentrations (30–120 pg/ml and 150–450 pg/ml, respectively) for up to 21 days. Collectively, we have demonstrated for the first time the feasibility of using a microfluidic chip system with continuous flow for the differentiation and extended culture of functional steroidogenic stem cell-derived EBs, the differentiation of EBs into cells expressing ovarian antigens in a microfluidic system, and the ability to cryopreserve this system with restoration of growth and functionality on thawing. These results present a platform for the development of a new therapeutic system for personalized medicine

The Use of Plant Steroids in Viral Disease Treatments: Current Status and Future Perspectives

Plants have been used for the prevention and treatment of diseases since the early days of humankind and constitute the natural sources of today’s modern medicine. Approximately one-quarter of approved drugs are derived from plants. Plant steroids are a group of biologically active secondary metabolites with a 5α and 5β gonane carbon skeleton. There is immense chemical diversity in plant steroids due to the side chains, oxidation status of the carbons in the tetracyclic core, and methyl groups. Plant steroids are classified into several groups based on their biological functions and structures, also on their mechanism of biosynthesis. All subtypes have been investigated for their anti-cancer, immunomodulatory, antiinflammatory, and anti-viral properties. The novel coronavirus disease (COVID-19) is caused by severe acute respiratory syndrome coronavirus (SARS-CoV-2), which carries an RNA genome. An intense effort has been made in terms of effective treatment strategies and vaccine development since it was declared a pandemic. Nucleoside analogs such as favipiravir and remdesivir are used to block RNA-dependent RNA polymerase enzymes. Other strategies including neuraminidase inhibitors, chloroquine, and hydroxychloroquine as immunomodulatory agents, stem cell and cytokine-based therapies are being conducted. One part of the therapies against SARS-CoV-2 is focused on the spike (S) protein of the virus that binds to the host receptor, angiotensin-converting enzyme 2 (ACE2). It has been suggested that SARS-CoV-2 S protein has a free fatty acidbinding pocket, and according to molecular simulations, steroids are ligands that bind to this pocket. Therefore, this review summarizes the plant steroid biological actions as well as their anti-viral potential against SARS-CoV-2 infection

On the Use of Electrooculogram for Efficient Human Computer Interfaces

The aim of this study is to present electrooculogram signals that can be used for human computer interface efficiently. Establishing an efficient alternative channel for communication without overt speech and hand movements is important to increase the quality of life for patients suffering from Amyotrophic Lateral Sclerosis or other illnesses that prevent correct limb and facial muscular responses. We have made several experiments to compare the P300-based BCI speller and EOG-based new system. A five-letter word can be written on average in 25 seconds and in 105 seconds with the EEG-based device. Giving message such as “clean-up” could be performed in 3 seconds with the new system. The new system is more efficient than P300-based BCI system in terms of accuracy, speed, applicability, and cost efficiency. Using EOG signals, it is possible to improve the communication abilities of those patients who can move their eyes

A Retrospective Case Study of Successful Translational Research: Gazelle Hb Variant Point-of-Care Diagnostic Device for Sickle Cell Disease

Evaluation researchers at Clinical and Translational Science Award (CTSA) hubs are conducting retrospective case studies to evaluate the translational research process. The objective of this study was to deepen knowledge of the translational process and identify contributors to successful translation. We investigated the successful translation of the HemeChip, a low-cost point-of-care diagnostic device for sickle cell disease, using a protocol for retrospective translational science case studies of health interventions developed by evaluators at the National Health Institutes (NIH) and CTSA hubs. Development of the HemeChip began in 2013 and evidence of device use and impact on public health is growing. Data collection methods included five interviews and a review of press, publications, patents, and grants. Barriers to translation included proving novelty, manufacturing costs, fundraising, and academic-industry relations. Facilitators to translation were CTSA pilot program funding, university resources, entrepreneurship training, due diligence, and collaborations. The barriers to translation, how they were overcome, and the key facilitators identified in this case study pinpoint areas for consideration in future funding mechanisms and the infrastructure required to enable successful translation

Guest editorial special section on sensor applications

[No abstract available

Aggregatable Distributed Key Generation

In this paper, we introduce a distributed key generation (DKG) protocol with aggregatable and publicly-verifiable transcripts. Compared with prior publicly-verifiable approaches, our DKG reduces the size of the final transcript and the time to verify it from O(n2) to O(nlogn) , where n denotes the number of parties. As compared with prior non-publicly-verifiable approaches, our DKG leverages gossip rather than all-to-all communication to reduce verification and communication complexity. We also revisit existing DKG security definitions, which are quite strong, and propose new and natural relaxations. As a result, we can prove the security of our aggregatable DKG as well as that of several existing DKGs, including the popular Pedersen variant. We show that, under these new definitions, these existing DKGs can be used to yield secure threshold variants of popular cryptosystems such as El-Gamal encryption and BLS signatures. We also prove that our DKG can be securely combined with a new efficient verifiable unpredictable function (VUF), whose security we prove in the random oracle model. Finally, we experimentally evaluate our DKG and show that the per-party overheads scale linearly and are practical. For 64 parties, it takes 71 ms to share and 359 ms to verify the overall transcript, while for 8192 parties, it takes 8 s and 42.2 s respectively

Specific c-Jun N-Terminal Kinase Inhibitor, JNK-IN-8 Suppresses Mesenchymal Profile of PTX-Resistant MCF-7 Cells through Modulating PI3K/Akt, MAPK and Wnt Signaling Pathways

Paclitaxel (PTX) is a widely used chemotherapeutic agent in the treatment of breast cancer, and resistance to PTX is a common failure of breast cancer therapy. Therefore, understanding the effective molecular targets in PTX-resistance gains importance in identifying novel strategies in successful breast cancer therapy approaches. The aim of the study was to investigate the functional role of PTX resistance on MCF-7 cell survival and proliferation related to PI3K/Akt and MAPK pathways. The generated PTX-resistant (PTX-res) MCF-7 cells showed enhanced cell survival, proliferation, and colony formation potential with decreased cell death compared to wt MCF-7 cells. PTX-res MCF-7 cells exhibited increased motility profile with EMT, PI3K/Akt, and MAPK pathway induction. According to the significant SAPK/JNK activation in PTX-res MCF-7 cells, specific c-Jun N-terminal kinase inhibitor, JNK-IN-8 is shown to suppress the migration potential of cells. Treatment of JNK inhibitor suppressed the p38 and SAPK/JNK and Vimentin expression. However, the JNK inhibitor further downregulated Wnt signaling members in PTX-res MCF-7 cells. Therefore, the JNK inhibitor JNK-IN-8 might be used as a potential therapy model to reverse PTX-resistance related to Wnt signaling