scholarly journals Precision Nanomedicine Volume 1 Issue 1 Table of Contents

2018 ◽  
Vol 1 (1) ◽  
pp. 1-5
Keyword(s):  
Drug Testing ◽  
Scavenger Receptor ◽  
Cell Communication ◽  
Superparamagnetic Iron Oxide ◽  
The Body ◽  
In Vivo Model ◽  
Hypersensitivity Reactions ◽  
Good Biocompatibility

The inaugural issue is introduced by several editorials: "The Story of Precision Nanomedicine-the Journal", "Balancing Interests of Science, Scientists, and the Publishing Business", and "Improving Innovation in Nano-Healthcare Funding". The Clinical Editor's comments on research papers: Prec. Nanomed. 2018, Apr; 1(1):18-42. Extracellular vesicles (EVs) are involved in various biological processes such as cargo trafficking, cell-cell communication, and signal transduction. The advances in nanotechnology have enabled researchers to utilize EVs for potential use in clinical applications, within the so-called precision medicine approach. In this review article, the authors discuss the techniques used in EV isolation in length, together with their applications in clinical diagnosis and therapeutics. Prec. Nanomed. 2018 Apr;1(1):63-75. Due to potential hypersensitivity reactions to nanodrugs, thorough testing is required before these drugs can be used in the clinical setting. Here the authors provide a succinct review on the use of pigs as a reliable in-vivo model for pre-clinical drug testing. Prec. Nanomed. 2018 Apr;1(1):76-85. One of the ways that nanoparticles are cleared in the body is via Kupffer cells. The authors of the next paper tested the role of scavenger receptor SR-AI/II in the clearance of dextran superparamagnetic iron oxide (SPIO) Feridex-IV® and dextran-coated SPIO nanoworms (SPIO NWs). Results here show that multiple pathways and mechanisms exist in nanoparticle clearance. Thus, further understanding of nanoparticle clearance would be required to prolong in vivo half-life. Prec. Nanomed. 2018 Apr;1(1):43-62. Liposomes have been used in clinical practice for some years, this delivery system often result in significant systemic effects due to hypersensitivity reactions, via the activation of the complement system. The authors here show good biocompatibility of Rad-PC-Rad liposomes in terms of complement activation and pro-inflammatory cytokines production in-vitro.

scholarly journals Increased Susceptibility of  Thymocytes to Apoptosis in Mice Lacking AIM, a Novel Murine Macrophage-derived Soluble Factor Belonging to the Scavenger Receptor Cysteine-rich Domain Superfamily

1999 ◽  
Vol 189 (2) ◽  
pp. 413-422 ◽  
Author(s):  
Toru Miyazaki ◽  
Yumiko Hirokami ◽  
Nobuyuki Matsuhashi ◽  
Hisakazu Takatsuka ◽  
Makoto Naito
Keyword(s):  
Scavenger Receptor ◽  
The Body ◽  
Murine Macrophage ◽  
Double Positive ◽  
Differential Signal ◽  
Rich Domain ◽  
Macrophage Scavenger Receptor ◽  
Cysteine Rich Domain

Apoptosis of cells must be regulated both positively and negatively in response to a variety of stimuli in the body. Various environmental stresses are known to initiate apoptosis via differential signal transduction cascades. However, induction of signals that may inhibit apoptosis is poorly understood, although a number of intracellular molecules that mediate inhibition of apoptosis have been identified. Here we present a novel murine macrophage-specific 54-kD secreted protein which inhibits apoptosis (termed AIM, for apoptosis inhibitor expressed by macrophages). AIM belongs to the macrophage scavenger receptor cysteine-rich domain superfamily (SRCR-SF), members of which share a highly homologous conserved cysteine-rich domain. In AIM-deficient mice, the thymocyte numbers were diminished to half those in wild-type mice, and CD4/CD8 double-positive (DP) thymocytes were strikingly more susceptible to apoptosis induced by both dexamethasone and irradiation in vivo. Recombinant AIM protein significantly inhibited cell death of DP thymocytes in response to a variety of stimuli in vitro. These results indicate that in the thymus, AIM functions in trans to induce resistance to apoptosis within DP cells, and thus supports the viability of DP thymocytes before thymic selection.

scholarly journals Mechanism of antrocytic connexin-43 autophagy degradation in oxygen-glucose deprivation and its effect on neuroinflammation

2019 ◽  
Author(s):  
Xinyu Wang ◽  
Liangshu Feng ◽  
Meiying Xin ◽  
Yulei Hao ◽  
Xu Wang ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Connexin 43 ◽  
Cell Communication ◽  
Glucose Deprivation ◽  
In Vivo Model ◽  
Oxygen Glucose Deprivation ◽  
Cx43 Protein ◽  
Protein Levels

Abstract Background : Connexin 43 (Cx43) are the most widely distributed gap junction proteins in the nervous system. Cx43 enables cell-to-cell communication and plays an important role in ion transport, substrate exchange and delivery of information , which have been implicated in cerebral ischemia injury. Our previous work revealed the relationships between Cx43 and glia-mediated neuroinflammation through the release of ATP in oxygen-glucose deprivation (OGD), which means degradation of Cx43 may improve neuroinflammatory damage during OGD injury . However, the roles of Cx43 degradation and neuroinflammation caused by OGD remain unclear. Methods: We used primary cultured astrocytes treated with OGD as an in vitro model of cerebral ischemia injury and we used middle cerebral artery occlusion (MCAO) model as an in vivo model of cerebral ischemia. HeLa cells were used in overexpression experiments. Cx43 protein levels were determined by western blotting. The interaction between Cx43 and related autophagy receptors was determined by co-immunoprecipitation and immunofluorescence. The gene knockdown (KD) of ATG5, OPTN, NDP52, PINK1 and Cx43 was applied by siRNA transfection. Related cytokines were detected by cytometric bead assay. Results: We found that Cx43 protein levels increased after ischemia in gene KD of ATG5, OPTN, NDP52 and PINK1 primary astrocytes. The interaction of Cx43 with OPTN, NDP52 and PINK1 was increased after cerebral ischemia injury in vitro and vivo. While the interaction was weakened after point mutation of Cx43 at Ser368, Tyr265 and Tyr247. Meanwhile, IL-10 upregulated during OGD after KD of ATG5, OPTN, NDP52 and PINK1 in astrocytes , while TNF downregulated during OGD after KD of ATG5, OPTN, NDP52 and PINK1 in astrocytes. Conclusions: Our results suggest that degradation of Cx43 is caused by selective autophagy during ischemia injury and the autophagy degradation of Cx43 plays important roles in neuroinflammation mediated by OGD injury. Treatment targeting Cx43 degradation pathway can improve neuroinflammation responses induced by OGD injury , which provide novel therapeutic strategies and crosstalk between autophagy and neuroinflammation.

scholarly journals Assessment of Pharmacokinetics and Metabolism Profiles of SCH 58261 in Rats Using Liquid Chromatography–Mass Spectrometric Method

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2209 ◽  
Author(s):  
Yuri Park ◽  
Min-Ho Park ◽  
Jin-Ju Byeon ◽  
Seok-Ho Shin ◽  
Byeong ill Lee ◽  
...  
Keyword(s):  
Bile Duct ◽  
Oral Administration ◽  
The Body ◽  
Metabolic Stability ◽  
In Vivo Model ◽  
Spectrometric Method ◽  
Mass Spectrometric Method ◽  
Sch 58261

5-Amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c) pyrimidine (SCH 58261) is one of the new chemical entities that has been developed as an adenosine A2A receptor antagonist. Although SCH 58261 has been reported to be beneficial, there is little information about SCH 58261 from a drug metabolism or pharmacokinetics perspective. This study describes the metabolism and pharmacokinetic properties of SCH 58261 in order to understand its behaviors in vivo. Rats were used as the in vivo model species. First, an LC–MS/MS method was developed for the determination of SCH 58261 in rat plasma. A GastroPlus™ simulation, in vitro microsomal metabolic stability, and bile duct-cannulated studies were also performed to understand its pharmacokinetic profile. The parameter sensitivity analysis of GastroPlus™ was used to examine the factors that influence exposure when the drug is orally administered. The factors are as follows: permeability, systemic clearance, renal clearance, and liver first-pass effect. In vitro microsomal metabolic stability indicates how much the drug is metabolized. The extrapolated hepatic clearance value of SCH 58261 was 39.97 mL/min/kg, indicating that the drug is greatly affected by hepatic metabolism. In vitro microsomal metabolite identification studies revealed that metabolites produce oxidized and ketone-formed metabolites via metabolic enzymes in the liver. The bile duct-cannulated rat study, after oral administration of SCH 58261, showed that a significant amount of the drug was excreted in feces. These results imply that the drug is not absorbed well in the body after oral administration. Taken together, SCH 58261 showed quite a low bioavailability when administered orally and this was likely due to significantly limited absorption, as well as high metabolism in vivo.

scholarly journals Current Advances in 3D Tissue and Organ Reconstruction

2021 ◽  
Vol 22 (2) ◽  
pp. 830
Author(s):  
Georgia Pennarossa ◽  
Sharon Arcuri ◽  
Teresina De Iorio ◽  
Fulvio Gandolfi ◽  
Tiziana A. L. Brevini
Keyword(s):  
Cell Biology ◽  
Drug Testing ◽  
Three Dimensional ◽  
3D Culture ◽  
In Vitro Models ◽  
The Body ◽  
Cellular Functions ◽  
Culture Systems

Bi-dimensional culture systems have represented the most used method to study cell biology outside the body for over a century. Although they convey useful information, such systems may lose tissue-specific architecture, biomechanical effectors, and biochemical cues deriving from the native extracellular matrix, with significant alterations in several cellular functions and processes. Notably, the introduction of three-dimensional (3D) platforms that are able to re-create in vitro the structures of the native tissue, have overcome some of these issues, since they better mimic the in vivo milieu and reduce the gap between the cell culture ambient and the tissue environment. 3D culture systems are currently used in a broad range of studies, from cancer and stem cell biology, to drug testing and discovery. Here, we describe the mechanisms used by cells to perceive and respond to biomechanical cues and the main signaling pathways involved. We provide an overall perspective of the most recent 3D technologies. Given the breadth of the subject, we concentrate on the use of hydrogels, bioreactors, 3D printing and bioprinting, nanofiber-based scaffolds, and preparation of a decellularized bio-matrix. In addition, we report the possibility to combine the use of 3D cultures with functionalized nanoparticles to obtain highly predictive in vitro models for use in the nanomedicine field.

GIT Physicochemical Modeling - A Critical Review

2006 ◽  
Vol 2 (4) ◽  
Author(s):  
'Michelle' Ji Yeon Yoo ◽  
Xiao Dong Chen
Keyword(s):  
The Body ◽  
In Vivo Model ◽  
Chemical Models ◽  
In Vivo Testing ◽  
Computer Controlled ◽  
Vitro Model ◽  
Key Aspects ◽  
Physiological And Biochemical

Many attempts to model the human gastrointestinal tract (GIT) were made since the beginning of the last decade. The main purpose was either to simulate an in vivo testing of drugs on animals or to investigate the viability of the probiotic intake. Two well-known physio-chemical models regarding the viability of the probiotics have been produced. In 1993, Molly et al. developed a simulator of the human intestinal microbial ecosystem (SHIME). Six reactors simulating the conditions of human stomach, duodenum/jejunum, ileum, caecum/ascending colon, transverse colon and descending colon were artificially developed. In 1995, Minekus et al. created a TNO gastro-intestinal model (TIM) with four computer-controlled chambers simulating the conditions of stomach, duodenum, jejunum and ileum. The simulated parameters included the body temperature, pH, salivary, gastric and intestinal mixing with peristaltic movements, secretions and absorption of water and small molecules. Despite the use of pharmacological, physiological and biochemical knowledge of the human and animal GIT and associated secretions, conflicting results such as the extremely low viability of probiotics were obtained. The failure of the above two models indicates the necessity of devising a suitable in vitro model that would be capable of simulating the digestion process as an exact replica of the actual in vivo model. In this paper, the key aspects of the above have been summarized and discussed.

scholarly journals Csf1r-GCaMP5 Reporter Mice Reveal Immune Cell Communication in Vitro and in Vivo

2021 ◽  
Author(s):  
N Taghdiri ◽  
D Calcagno ◽  
Z Fu ◽  
K Huang ◽  
RH Kohler ◽  
...  
Keyword(s):  
Communication Networks ◽  
Immune Cells ◽  
Immune Cell ◽  
Cell Communication ◽  
Spatiotemporal Dynamics ◽  
The Body ◽  
Excitable Cells ◽  
Communication Events

ABSTRACTInterconnected cells are responsible for emergent functions ranging from cognition in the brain to cyclic contraction in the heart. In electrically excitable cells, methods for studying cell communication are highly advanced, but in non-excitable cells, generalized methods for studying cell communication are less mature. Immune cells have generally been classified as non-excitable cells with diverse pathophysiologic roles that span every tissue in the body, yet little is known about their interconnectedness because assays are destructive and have low temporal resolution. In this work, we hypothesize that non-excitable immune cells are functionally interconnected in previously unrecognized cell communication networks. To test the hypothesis, we created a hematopoietic calcium reporter mouse (Csf1r-Cre × GCaMP5) and non-destructively quantified the spatiotemporal dynamics of intracellular calcium in vitro and in vivo. In vitro, bone marrow derived macrophages calcium reporters reveal that fatal immune stimulatory DNA-sensing induces rapid intercellular communication to neighboring cells. In vivo, using intravital microscopy through a dorsal window chamber in the context of MC38-H2B-mCherry tumors, Csf1r-GCaMP5 reporters exhibit spatiotemporal dynamics consistent with cell communication. We present a theoretical framework and analysis pipeline for identifying spatiotemporal locations of “excess synchrony” of calcium spiking as a means of inferring previously unrecognized cell communication events. Together, these methods provide a toolkit for investigating known and as-yet-undiscovered cell communication events in vitro and in vivo.

scholarly journals Discrepancies in the in vitro and in vivo role of scavenger receptors in clearance of nanoparticles by Kupffer cells

2018 ◽  
Vol 1 (1) ◽  
pp. 76-84 ◽  
Author(s):  
Guankui Wang ◽  
Ernest Groman ◽  
Dmitri Simberg
Keyword(s):  
Kupffer Cells ◽  
Half Life ◽  
Scavenger Receptor ◽  
Superparamagnetic Iron Oxide ◽  
Macrophage Scavenger Receptor ◽  
Polyinosinic Acid ◽  
Efficient Uptake

Nanoparticles are recognized and cleared by Kupffer cells (KCs) in the liver. This process complicates the development of targeted nanoparticles because of significant reduction of number of nanoparticles that can reach target tissues. Macrophage scavenger receptor SR type AI/II is the central phagocytic receptor that has been shown to promote in vitro uptake of many nanoparticle types. In this paper, the authors set out to clarify the role of SR-AI/II in the in vivo liver clearance of 10kDa dextran superparamagnetic iron oxide (SPIO) Feridex-IV® and 20kDa dextran-coated SPIO nanoworms (SPIO NWs). Feridex showed efficient SR-AI/II-dependent uptake by isolated KCs in vitro, whereas SPIO NWs showed no uptake by KCs. Both Feridex and SPIO NWs showed a very short and nearly identical circulation half-life and efficient uptake by KCs in vivo. The SR-AI/II inhibitor, polyinosinic acid, prolonged the circulation half-life of both Feridex and SPIO NWs, but did not reduce the KC uptake. The circulation half-life and KC uptake of Feridex and SPIO NWs were identical in SR-AI/II-deficient mice and wild-type mice. These data suggest: (1) there is a limited correlation between in vitro and in vivo uptake mechanisms of nanoparticles in KCs; and (2) redundant, SR-AI/II independent mechanisms play a significant role in the nanoparticle recognition by KCs in vivo. Understanding the complexity of nanoparticle clearance assays and mechanisms is an important step to improving the design of “stealthy” nanoparticles.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

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.

Репрограммированые in vitro на М3 фенотип макрофаги останавливают рост солидной карциномы in vivo

2018 ◽  
pp. 41-46
Author(s):  
А.А. Раецкая ◽  
С.В. Калиш ◽  
С.В. Лямина ◽  
Е.В. Малышева ◽  
О.П. Буданова ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Antitumor Effect ◽  
Tumor Development ◽  
Significant Inhibition ◽  
The Body ◽  
Ehrlich Carcinoma ◽  
Solid Carcinoma ◽  
Ec Cells

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.

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