scholarly journals Automated Reactive Accelerated Aging for Rapid In Vitro Evaluation of Neural Implants Performance

2017 ◽  
Author(s):  
Matthew G. Street ◽  
Cristin G. Welle ◽  
Pavel A. Takmakov

AbstractObjectiveNovel therapeutic applications for neural implants require miniaturized devices. Pilot clinical studies suggest that rapid failure of the miniaturized neural implants in the body presents a major challenge for this type of technology. Miniaturization imposes stricter requirements for reliability of materials and designs. Evaluation of neural implant performance over clinically relevant timescales presents time-and cost-prohibitive challenges for animal models.ApproachIn vitro reactive accelerated aging (RAA) was developed to expedite durability testing of these devices. RAA simulates an aggressive physiological environment associated with an immune response and implicated in device failure. It uses hydrogen peroxide, which mimics reactive oxygen species (ROS), and high temperature to accelerate chemical reactions that lead to device degradation. RAA accurately simulates the degradation pattern of neural implants observed in vivo, but requires daily maintenance and is prone to variability in performance.Main resultsThis work introduces automated reactive accelerated aging (aRAA) that is compatible with multiplexing. The core of aRAA is electrochemical detection for feedback control of hydrogen peroxide concentration, implemented with simple off-the shelf components.SignificanceaRAA allows multiple parallel experiments for a high-throughput optimization of reactive aging conditions to more quickly and more rigorously simulate the in vivo environment. aRAA is a cost-effective tool for rapid in vitro evaluation of durability of neural implants, ultimately expediting the development of a new generation of miniaturized devices with long functional lifespans.

2000 ◽  
Vol 6 (S2) ◽  
pp. 834-835
Author(s):  
Robert W. Bradford, Chairman ◽  
Curriculum Oversight

The typical aging processes can be characterized by a gradual alteration and essential breakdown of the functional systems of the body. Numerous factors play important roles in the alterations of these pathways from biochemical individuality and genetic predisposition to environmental insults and deficiency states.1 Clinical research, as but one example, has clearly documented the role of free radicals (ROS) or oxidative injury in disease and aging affecting the body's basic cellular structures.The objective of functional or health assessments is to be able to detect in vivo stresses and imbalances in the biological systems, while the patient is asymptomatic, so that early therapeutic intervention can resolve the problems prior to disease onset or accelerated aging. The ability to assess risk factors and treat the sub-clinical metabolic toxicities, deficiency states, hormonal imbalances, oxidative injury (ROS), immunodeficiencies, enzyme down regulations, antioxidant status, metal toxicities, cardiovascular stresses, organ reserves/stresses and detox systems in a low-complexity, cost-effective office procedure is true preventive medicine.


Author(s):  
Д.А. Еникеев ◽  
К.О. Кузнецов ◽  
О.А. Еникеев ◽  
Д.Р. Кузнецова ◽  
Э.Н. Хисамов ◽  
...  

В статье приведен обзор литературы за последние 100 лет. Затронута история открытия и применения перекиси водорода в различные годы. Подробно описаны химические и физические свойства перекиси водорода, её механизмы действия in vivo и in vitro. Затронута тема образования перекиси водорода в собственных клетках организма человека и животных, описаны физиологические функции эндогенной перекиси водорода в человеческом теле. The article provides a review of literature for the past 100 years; touches on the history of discovery and the use of hydrogen peroxide in different years; describes in detail chemical and physical properties of hydrogen peroxide, and its mechanisms of action in vivo and in vitro. The review addresses the formation of hydrogen peroxide in human and animal cells and describes physiological functions of endogenous hydrogen peroxide in the human body.


2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.


Author(s):  
А.А. Раецкая ◽  
С.В. Калиш ◽  
С.В. Лямина ◽  
Е.В. Малышева ◽  
О.П. Буданова ◽  
...  

Цель исследования. Доказательство гипотезы, что репрограммированные in vitro на М3 фенотип макрофаги при введении в организм будут существенно ограничивать развитие солидной карциномы in vivo . Методика. Рост солидной опухоли инициировали у мышей in vivo путем подкожной инъекции клеток карциномы Эрлиха (КЭ). Инъекцию макрофагов с нативным М0 фенотипом и с репрограммированным M3 фенотипом проводили в область формирования солидной КЭ. Репрограммирование проводили с помощью низких доз сыворотки, блокаторов факторов транскрипции STAT3/6 и SMAD3 и липополисахарида. Использовали две схемы введения макрофагов: раннее и позднее. При раннем введении макрофаги вводили на 1-е, 5-е, 10-е и 15-е сут. после инъекции клеток КЭ путем обкалывания макрофагами с четырех сторон область развития опухоли. При позднем введении, макрофаги вводили на 10-е, 15-е, 20-е и 25-е сут. Через 15 и 30 сут. после введения клеток КЭ солидную опухоль иссекали и измеряли ее объем. Эффект введения макрофагов оценивали качественно по визуальной и пальпаторной характеристикам солидной опухоли и количественно по изменению ее объема по сравнению с группой без введения макрофагов (контроль). Результаты. Установлено, что M3 макрофаги при раннем введении от начала развития опухоли оказывают выраженный антиопухолевый эффект in vivo , который был существенно более выражен, чем при позднем введении макрофагов. Заключение. Установлено, что введение репрограммированных макрофагов M3 ограничивает развитие солидной карциномы в экспериментах in vivo . Противоопухолевый эффект более выражен при раннем введении М3 макрофагов. Обнаруженные в работе факты делают перспективным разработку клинической версии биотехнологии ограничения роста опухоли, путем предварительного программирования антиопухолевого врожденного иммунного ответа «в пробирке». Aim. To verify a hypothesis that macrophages reprogrammed in vitro to the M3 phenotype and injected into the body substantially restrict the development of solid carcinoma in vivo . Methods. Growth of a solid tumor was initiated in mice in vivo with a subcutaneous injection of Ehrlich carcinoma (EC) cells. Macrophages with a native M0 phenotype or reprogrammed towards the M3 phenotype were injected into the region of developing solid EC. Reprogramming was performed using low doses of serum, STAT3/6 and SMAD3 transcription factor blockers, and lipopolysaccharide. Two schemes of macrophage administration were used: early and late. With the early administration, macrophages were injected on days 1, 5, 10, and 15 following the injection of EC cells at four sides of the tumor development area. With the late administration, macrophages were injected on days 10, 15, 20, and 25. At 15 and 30 days after the EC cell injection, the solid tumor was excised and its volume was measured. The effect of macrophage administration was assessed both qualitatively by visual and palpation characteristics of solid tumor and quantitatively by changes in the tumor volume compared with the group without the macrophage treatment. Results. M3 macrophages administered early after the onset of tumor development exerted a pronounced antitumor effect in vivo , which was significantly greater than the antitumor effect of the late administration of M3 macrophages. Conclusion. The observed significant inhibition of in vivo growth of solid carcinoma by M3 macrophages makes promising the development of a clinical version of the biotechnology for restriction of tumor growth by in vitro pre-programming of the antitumor, innate immune response.


2020 ◽  
Vol 26 (45) ◽  
pp. 5783-5792
Author(s):  
Kholood Abid Janjua ◽  
Adeeb Shehzad ◽  
Raheem Shahzad ◽  
Salman Ul Islam ◽  
Mazhar Ul Islam

There is compelling evidence that drug molecules isolated from natural sources are hindered by low systemic bioavailability, poor absorption, and rapid elimination from the human body. Novel approaches are urgently needed that could enhance the retention time as well as the efficacy of natural products in the body. Among the various adopted approaches to meet this ever-increasing demand, nanoformulations show the most fascinating way of improving the bioavailability of dietary phytochemicals through modifying their pharmacokinetics and pharmacodynamics. Curcumin, a yellowish pigment isolated from dried ground rhizomes of turmeric, exhibits tremendous pharmacological effects, including anticancer activities. Several in vitro and in vivo studies have shown that curcumin mediates anticancer effects through the modulation (upregulation and/or downregulations) of several intracellular signaling pathways both at protein and mRNA levels. Scientists have introduced multiple modern techniques and novel dosage forms for enhancing the delivery, bioavailability, and efficacy of curcumin in the treatment of various malignancies. These novel dosage forms include nanoparticles, liposomes, micelles, phospholipids, and curcumin-encapsulated polymer nanoparticles. Nanocurcumin has shown improved anticancer effects compared to conventional curcumin formulations. This review discusses the underlying molecular mechanism of various nanoformulations of curcumin for the treatment of different cancers. We hope that this study will make a road map for preclinical and clinical investigations of cancer and recommend nano curcumin as a drug of choice for cancer therapy.


2018 ◽  
Vol 18 (5) ◽  
pp. 321-368 ◽  
Author(s):  
Juan A. Bisceglia ◽  
Maria C. Mollo ◽  
Nadia Gruber ◽  
Liliana R. Orelli

Neglected diseases due to the parasitic protozoa Leishmania and Trypanosoma (kinetoplastids) affect millions of people worldwide, and the lack of suitable treatments has promoted an ongoing drug discovery effort to identify novel nontoxic and cost-effective chemotherapies. Polyamines are ubiquitous small organic molecules that play key roles in kinetoplastid parasites metabolism, redox homeostasis and in the normal progression of cell cycles, which differ from those found in the mammalian host. These features make polyamines attractive in terms of antiparasitic drug development. The present work provides a comprehensive insight on the use of polyamine derivatives and related nitrogen compounds in the chemotherapy of kinetoplastid diseases. The amount of literature on this subject is considerable, and a classification considering drug targets and chemical structures were made. Polyamines, aminoalcohols and basic heterocycles designed to target the relevant parasitic enzyme trypanothione reductase are discussed in the first section, followed by compounds directed to less common targets, like parasite SOD and the aminopurine P2 transporter. Finally, the third section comprises nitrogen compounds structurally derived from antimalaric agents. References on the chemical synthesis of the selected compounds are reported together with their in vivo and/or in vitro IC50 values, and structureactivity relationships within each group are analyzed. Some favourable structural features were identified from the SAR analyses comprising protonable sites, hydrophobic groups and optimum distances between them. The importance of certain pharmacophoric groups or amino acid residues in the bioactivity of polyamine derived compounds is also discussed.


Foods ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 315
Author(s):  
Zhenxing Wang ◽  
Zongcai Tu ◽  
Xing Xie ◽  
Hao Cui ◽  
Kin Weng Kong ◽  
...  

This study aims to evaluate the bioactive components, in vitro bioactivities, and in vivo hypoglycemic effect of P. frutescens leaf, which is a traditional medicine-food homology plant. P. frutescens methanol crude extract and its fractions (petroleum ether, chloroform, ethyl acetate, n-butanol fractions, and aqueous phase residue) were prepared by ultrasound-enzyme assisted extraction and liquid–liquid extraction. Among the samples, the ethyl acetate fraction possessed the high total phenolic (440.48 μg GAE/mg DE) and flavonoid content (455.22 μg RE/mg DE), the best antioxidant activity (the DPPH radical, ABTS radical, and superoxide anion scavenging activity, and ferric reducing antioxidant power were 1.71, 1.14, 2.40, 1.29, and 2.4 times higher than that of control Vc, respectively), the most powerful α-glucosidase inhibitory ability with the IC50 value of 190.03 μg/mL which was 2.2-folds higher than control acarbose, the strongest proliferative inhibitory ability against MCF-7 and HepG2 cell with the IC50 values of 37.92 and 13.43 μg/mL, which were considerable with control cisplatin, as well as certain inhibition abilities on acetylcholinesterase and tyrosinase. HPLC analysis showed that the luteolin, rosmarinic acid, rutin, and catechin were the dominant components of the ethyl acetate fraction. Animal experiments further demonstrated that the ethyl acetate fraction could significantly decrease the serum glucose level, food, and water intake of streptozotocin-induced diabetic SD rats, increase the body weight, modulate their serum levels of TC, TG, HDL-C, and LDL-C, improve the histopathology and glycogen accumulation in liver and intestinal tissue. Taken together, P. frutescens leaf exhibits excellent hypoglycemic activity in vitro and in vivo, and could be exploited as a source of natural antidiabetic agent.


2021 ◽  
Vol 8 (3) ◽  
pp. 39
Author(s):  
Britani N. Blackstone ◽  
Summer C. Gallentine ◽  
Heather M. Powell

Collagen is a key component of the extracellular matrix (ECM) in organs and tissues throughout the body and is used for many tissue engineering applications. Electrospinning of collagen can produce scaffolds in a wide variety of shapes, fiber diameters and porosities to match that of the native ECM. This systematic review aims to pool data from available manuscripts on electrospun collagen and tissue engineering to provide insight into the connection between source material, solvent, crosslinking method and functional outcomes. D-banding was most often observed in electrospun collagen formed using collagen type I isolated from calfskin, often isolated within the laboratory, with short solution solubilization times. All physical and chemical methods of crosslinking utilized imparted resistance to degradation and increased strength. Cytotoxicity was observed at high concentrations of crosslinking agents and when abbreviated rinsing protocols were utilized. Collagen and collagen-based scaffolds were capable of forming engineered tissues in vitro and in vivo with high similarity to the native structures.


Nanophotonics ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 3023-3034
Author(s):  
Weiyuan Liang ◽  
Dou Wang ◽  
Xiaohui Ren ◽  
Chenchen Ge ◽  
Hanyue Wang ◽  
...  

AbstractTwo-dimensional black phosphorus (BP) has been demonstrated to be promising in photoelectronic devices, electrode materials, and biomedicine owing to its outstanding properties. However, the application of BP has been hindered by harsh preparation conditions, high costs, and easy degradation in ambient condition. Herein, we report a facile and cost-effective strategy for synthesis of orthorhombic phase BP and a kind of BP-reduced graphene oxide (BP/rGO) hybrids in which BP remains stable for more than 4 weeks ascribed to the formation of phosphorus-carbon covalent bonds between BP and rGO as well as the protection effect of the unique wrinkle morphology of rGO nanosheets. Surface modification BP/rGO hybrids (PEGylated BP/rGO) exhibit excellent photothermal performance with photothermal conversion efficiency as high as 57.79% at 808 nm. The BP/rGO hybrids exhibit enhanced antitumor effects both in vitro and in vivo, showing promising perspectives in biomedicine.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Zeping Qiu ◽  
Jingwen Zhao ◽  
Fanyi Huang ◽  
Luhan Bao ◽  
Yanjia Chen ◽  
...  

AbstractMyocardial fibrosis and ventricular remodeling were the key pathology factors causing undesirable consequence after myocardial infarction. However, an efficient therapeutic method remains unclear, partly due to difficulty in continuously preventing neurohormonal overactivation and potential disadvantages of cell therapy for clinical practice. In this study, a rhACE2-electrospun fibrous patch with sustained releasing of rhACE2 to shape an induction transformation niche in situ was introduced, through micro-sol electrospinning technologies. A durable releasing pattern of rhACE2 encapsulated in hyaluronic acid (HA)—poly(L-lactic acid) (PLLA) core-shell structure was observed. By multiple in vitro studies, the rhACE2 patch demonstrated effectiveness in reducing cardiomyocytes apoptosis under hypoxia stress and inhibiting cardiac fibroblasts proliferation, which gave evidence for its in vivo efficacy. For striking mice myocardial infarction experiments, a successful prevention of adverse ventricular remodeling has been demonstrated, reflecting by improved ejection fraction, normal ventricle structure and less fibrosis. The rhACE2 patch niche showed clear superiority in long term function and structure preservation after ischemia compared with intramyocardial injection. Thus, the micro-sol electrospun rhACE2 fibrous patch niche was proved to be efficient, cost-effective and easy-to-use in preventing ventricular adverse remodeling.


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