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Pre-conditioning of adipose-derived stromal cells (ASCs) by tuning the cellular microenvironment during expansion has the potential to modulate their pro-regenerative functionality. The current study investigated the effects of microcarrier composition (decellularized adipose tissue versus collagen), oxygen tension (2% versus ~20% O2) and stirring rate (static, 20, 40 rpm) on human ASCs cultured within spinner flask bioreactors. Dynamic culturing under 20% O2 resulted in more consistent cell growth on both microcarrier substrates, leading to increases in microcarrier contraction and stiffness. Culturing on the microcarriers modulated the hASC immunophenotype, with varying CD90 and CD26 expression levels observed under the different culture conditions. Interestingly, the gene expression levels of a range of pro-angiogenic and immunomodulatory factors were enhanced in the hASCs cultured on the collagen microcarriers at 20 rpm and 2% O2, supporting that the conditions within stirred bioreactors can be tuned to pre-condition hASCs for applications in vascular regeneration.

Pringle maneuver (PM) is a very common procedure in liver surgeries and comprises the temporary occlusion of hepatic artery and hepatic portal vein through non-traumatic clamping, followed by reperfusion. However, liver ischemia-reperfusion provokes hepatic alterations that could have impact on remote organs, namely on the heart. In this way, several strategies have been developed in attempt to counteract these consequences. Thus, the aim of this dissertation was to evaluate the impact of PM on heart remodelling and the effect of endurance exercise training as a preventive approach, through the histologic analysis and the molecular assessment of metabolism, oxidative stress and inflammation. For this purpose, healthy Wistar male rats were submitted to an endurance exercise program (30 m/min, 60 min/day, 9 days), followed by a liver ischemia-reperfusion protocol (30 min ischemia, 24 h reperfusion). The results suggest that both PM and exercise did not provoke significant alterations in metabolic substrate utilization (glucose and fatty acids), susceptibility to oxidative stress and local inflammation on the right ventricle (RV). In overall, data suggest that the PM-induced liver injury did not promote the remodelling of RV. In the future, it would be important to perform morphometric analysis and to deeper comprehend nitric oxide metabolism in RV, extend the study to both male and female and also to left ventricle remodelling, to better characterize the cardiac response to the interplay between liver ischemia-reperfusion and exercise training. A Manobra de Pringle (MP) é uma abordagem muito comum em cirurgias hepáticas e consiste na oclusão temporária do fluxo sanguíneo da artéria hepática e veia porta hepática, através de clampagem, seguida de reperfusão. Contudo, a isquemia-reperfusão do fígado provoca adaptações hepáticas que podem ter impacto noutros órgãos, nomeadamente no coração, pelo que se tem tentado desenvolver estratégias para prevenir as consequências tanto a nível do fígado como a nível de outros órgãos afetados. Assim, esta dissertação teve como objetivo avaliar o impacto da MP no coração e o efeito preventivo do exercício físico de endurance, pela análise histológica e pela análise de marcadores de metabolismo, stress oxidativo e inflamação. Para o efeito, submeteram-se ratos Wistar machos saudáveis a um programa de exercício físico de endurance (30 m/min, 60 min/dia, 9 dias) e a um protocolo de isquemiareperfusão hepática (30 min isquemia, 24 h reperfusão). Os resultados da análise do ventrículo direito (VD) sugerem que a MP bem como o exercício não promoveram alterações de utilização de substrato energético (glucose e ácidos gordos), suscetibilidade a stress oxidativo e inflamação local. No global, os resultados mostram que a lesão hepática provocada pela MP não teve impacto na remodelação do coração. No futuro, será importante efetuar a análise morfométrica e avaliar o metabolismo do óxido nítrico no VD, bem como estender estas e outras análises ao estudo do ventrículo esquerdo e considerar tanto machos como fêmeas, para melhor caracterizar a resposta cardíaca à interação entre a MP e o exercício físico. Mestrado em Bioquímica

Sesbania aculeata is a multipurpose legume crop grown primarily for green manuring in the rice-based cropping system. Besides this, it is an industrial crop and is also used as food in many parts of the world. The present work reports for optimization of various parameters (growth medium, plant growth regulators, pre-conditioning, orientation of explant, and presence of thiol compounds) affecting in vitro regeneration using mature cotyledon explants. The 5-day-old mature cotyledon explants excised from seedlings grown on Murashige and Skoog (MS) salts and Gamborg (B5) vitamins medium containing 15 μM 6-benzylaminopurine were cultured with its adaxial side facing on medium containing 2.5 μM 6-benzylaminopurine and 50 mg/L thiourea and produced multiple shoots (7 ‒ 8) in 100% cultures within 28 days. Healthy shoots were rooted on half-strength Murashige and Skoog (MS) salts and full-strength vitamins medium augmented with 2.5 μM indole-3-butyric acid.

International audience; The FRiM fractal operator belongs to a family of operators, called ASAP, defined by an ordered selection of nearest neighbors. This generalization provides means to improve upon the good properties of FRiM. We propose a fast algorithm to build an ASAP operator mimicking the fractal structure of FRiM for pupils of any size and geometry and to learn the sparse coefficients from empirical data. We empirically show the good approximation by ASAP of correlated statistics and the benefits of ASAP for solving phase restoration problems.

Mesenchymal stem/stromal cells (MSCs) have attracted a great deal of attention in the last decades, initially for their ability to differentiate into other various cell types, then later for their ability to release various biological factors with therapeutic effects, such as the mediation of cellular regeneration and protection and immunomodulation, highlighting their repertoire of attributes. These properties of MSCs have seen them used in various clinical trials to treat various human diseases. Recently, MSCs have been utilized as a factory of cells to produce and secrete extracellular vesicles (EVs), as it has been shown that MSC-derived EVs may carry part of the therapeutic effects of their parent cells. Obviously, this is advantageous as it would be mean that cell-free therapies laced with the therapeutic effects of MSCs could be possible. EVs can be termed as apoptotic bodies, microvesicle bodies, or exosomes, depending on their size. Interestingly and unsurprisingly, as it is common knowledge in the field that MSCs respond differently depending on their microenvironment, it has been found that MSCs can be pre-conditioned to produce and secrete EVs with different therapeutic properties. Herein, recent findings highlighting the therapeutic potential of MSC-derived EVs will be discussed, specifically MSC-derived exosomes.

Induced pluripotent stem cell (iPSC) derived mesenchymal stem cells (iMSCs) represent a promising source of progenitor cells for approaches in the field of bone regeneration. Bone formation is a multi-step process in which osteogenesis and angiogenesis are both involved. Many reports show that the secretome of mesenchymal stromal stem cells (MSCs) influences the microenvironment upon injury, promoting cytoprotection, angiogenesis, and tissue repair of the damaged area. However, the effects of iPSC-derived MSCs secretome on angiogenesis have seldom been investigated. In the present study, the angiogenic properties of IFN-γ pre-conditioned iMSC secretomes were analyzed. We detected a higher expression of the pro-angiogenic genes and proteins of iMSCs and their secretome under IFN-γ and hypoxic stimulation (IFN-H). Tube formation and wound healing assays revealed a higher angiogenic potential of HUVECs in the presence of IFN-γ conditioned iMSC secretome. Sprouting assays demonstrated that within Coll/HA scaffolds, HUVECs spheroids formed significantly more and longer sprouts in the presence of IFN-γ conditioned iMSC secretome. Through gene expression analyses, pro-angiogenic genes (FLT-1, KDR, MET, TIMP-1, HIF-1α, IL-8, and VCAM-1) in HUVECs showed a significant up-regulation and down-regulation of two anti-angiogenic genes (TIMP-4 and IGFBP-1) compared to the data obtained in the other groups. Our results demonstrate that the iMSC secretome, pre-conditioned under inflammatory and hypoxic conditions, induced the highest angiogenic properties of HUVECs. We conclude that pre-activated iMSCs enhance their efficacy and represent a suitable cell source for collagen/hydroxyapatite with angiogenic properties.

Induced pluripotent stem cell (iPSC) derived mesenchymal stem cells (iMSCs) represent a promising source of progenitor cells for approaches in the field of bone regeneration. Bone formation is a multi-step process in which osteogenesis and angiogenesis are both involved. Many reports show that the secretome of mesenchymal stromal stem cells (MSCs) influences the microenvironment upon injury, promoting cytoprotection, angiogenesis, and tissue repair of the damaged area. However, the effects of iPSC-derived MSCs secretome on angiogenesis have seldom been investigated. In the present study, the angiogenic properties of IFN-γ pre-conditioned iMSC secretomes were analyzed. We detected a higher expression of the pro-angiogenic genes and proteins of iMSCs and their secretome under IFN-γ and hypoxic stimulation (IFN-H). Tube formation and wound healing assays revealed a higher angiogenic potential of HUVECs in the presence of IFN-γ conditioned iMSC secretome. Sprouting assays demonstrated that within Coll/HA scaffolds, HUVECs spheroids formed significantly more and longer sprouts in the presence of IFN-γ conditioned iMSC secretome. Through gene expression analyses, pro-angiogenic genes (FLT-1, KDR, MET, TIMP-1, HIF-1α, IL-8, and VCAM-1) in HUVECs showed a significant up-regulation and down-regulation of two anti-angiogenic genes (TIMP-4 and IGFBP-1) compared to the data obtained in the other groups. Our results demonstrate that the iMSC secretome, pre-conditioned under inflammatory and hypoxic conditions, induced the highest angiogenic properties of HUVECs. We conclude that pre-activated iMSCs enhance their efficacy and represent a suitable cell source for collagen/hydroxyapatite with angiogenic properties., S.W. was financed by the China Scholarship Council (CSC) (grant 201908080045).

Human bone marrow mesenchymal stem cell derived-extracellular vesicles (HBMSC-EV) are known for their regenerative and anti-inflammatory effects in animal models of myocardial ischemia. However, it is not known whether the efficacy of the EVs can be modulated by pre-conditioning of HBMSC by exposing them to either starvation or hypoxia prior to EV collection. HBMSC-EVs were isolated following normoxia starvation (NS), normoxia non-starvation (NNS), hypoxia starvation (HS), or hypoxia non-starvation (HNS) pre-conditioning. The HBMSC-EVs were characterized by nanoparticle tracking analysis, electron microscopy, Western blot, and proteomic analysis. Comparative proteomic profiling revealed that starvation pre-conditioning led to a smaller variety of proteins expressed, with the associated lesser effect of normoxia versus hypoxia pre-conditioning. In the absence of starvation, normoxia and hypoxia pre-conditioning led to disparate HBMSC-EV proteomic profiles. HNS HBMSC-EV was found to have the greatest variety of proteins overall, with 74 unique proteins, the greatest number of redox proteins, and pathway analysis suggestive of improved angiogenic properties. Future HBMSC-EV studies in the treatment of cardiovascular disease may achieve the most therapeutic benefits from hypoxia non-starved pre-conditioned HBMSC. This study was limited by the lack of functional and animal models of cardiovascular disease and transcriptomic studies.

Land salinization, resulting from the ongoing climate change phenomena, is having an increasing impact on coastal ecosystems like salt marshes. Although halophyte species can live and thrive in high salinities, they experience differences in their salt tolerance range, being this a determining factor in the plant distribution and frequency throughout marshes. Furthermore, intraspecific variation to NaCl response is observed in high-ranging halophyte species at a population level. The present study aims to determine if the environmental history, namely heavy metal pre-conditioning, can have a meaningful influence on salinity tolerance mechanisms of Spartina patens, a highly disperse grass invader in the Mediterranean marshes. For this purpose, individuals from pristine and heavy metal contaminated marsh populations were exposed to a high-ranging salinity gradient, and their intraspecific biophysical and biochemical feedbacks were analyzed. When comparing the tolerance mechanisms of both populations, S. patens from the contaminated marsh appeared to be more resilient and tolerant to salt stress, this was particularly present at the high salinities. Consequently, as the salinity increases in the environment, the heavy metal contaminated marsh may experience a more resilient and better adapted S. patens community. Therefore, the heavy metal pre-conditioning of salt mash populations appears to be able to create intraspecific physiological variations at the population level that can have a great influence on marsh plant distribution outcome. Fundação para a Ciência e a Tecnologia (FCT) UIDB/04292/2020, UID/MULTI/04046/2019, PTDC/CTA-AMB/30056/2017, CEECIND/00511/2017 Ministerio de Ciencia e Innovación (MICIN) 16-01-04-FMP-0014

The review focuses on the neuroprotective mechanisms of therapeutic hypothermia from the standpoint of metabolic depression and genomic reprogramming of neurons that develop when brain temperature decreases.The concept of hypothermic pre-conditioning based on the development of typical nonspecific reactions for the formation of the cytoprotective phenotype of neurons due to potentially dangerous stimuli, such as ischemia, reperfusion, and hypothermia, was used to explain the effects of low temperatures. The data confirming the role of therapeutic cerebral hypothermia as a technique of selective brain exposure to mild cold for the neuroprotection and correction of temperature balance disorders are shown.The approach to therapeutic hypothermia as a hypothermic pre-conditioning allows to significantly expand the scope of its use in various procedural variants.

Mesenchymal stromal cells (MSCs) represent a promising treatment for immune-related diseases due to their diverse immunomodulatory paracrine functions. However, progress of culture-expanded MSCs is hindered by inconsistent cell function, poor localization, and insufficient retention when administered as suspended cell injections, thus placing spatiotemporal dosing constraints on therapeutic functions. To address these limitations, we introduce the combination of in vitro interferon-gamma (IFN-γ) priming, a key stimulator of MSC immunosuppressive potency, and thermoresponsive cultureware to harvest cultured MSCs as directly transplantable scaffold-free immunosuppressive cell sheets. Here, we demonstrate that MSC sheets produced with IFN-γ priming upregulate expression of immunosuppressive factors indoleamine 2,3-dioxygenase (IDO-1), interleukin-10 (IL-10), programmed death ligand-1 (PD-L1), and prostaglandin E2 (PGE2) in both dose- and duration-dependent manners. In addition, IFN-γ primed MSC sheets showed increased ability to inhibit T-cell proliferation via indirect and direct contact, specifically related to increased IDO-1 and PGE2 concentrations. Furthermore, this study’s use of human clinical-grade single-cell-derived clonal bone marrow-derived MSCs, contributes to the future translatability and clinical relevancy of the produced sheets. Ultimately, these results present the combination of IFN-γ priming and MSC sheets as a new strategy to improve MSC-mediated treatment of localized inflammatory diseases.

Land salinization, resulting from the ongoing climate change phenomena, is having an increasing impact on coastal ecosystems like salt marshes. Although halophyte species can live and thrive in high salinities, they experience differences in their salt tolerance range, being this a determining factor in the plant distribution and frequency throughout marshes. Furthermore, intraspecific variation to NaCl response is observed in high-ranging halophyte species at a population level. The present study aims to determine if the environmental history, namely heavy metal pre-conditioning, can have a meaningful influence on salinity tolerance mechanisms of Spartina patens, a highly disperse grass invader in the Mediterranean marshes. For this purpose, individuals from pristine and heavy metal contaminated marsh populations were exposed to a high-ranging salinity gradient, and their intraspecific biophysical and biochemical feedbacks were analyzed. When comparing the tolerance mechanisms of both populations, S. patens from the contaminated marsh appeared to be more resilient and tolerant to salt stress, this was particularly present at the high salinities. Consequently, as the salinity increases in the environment, the heavy metal contaminated marsh may experience a more resilient and better adapted S. patens community. Therefore, the heavy metal pre-conditioning of salt mash populations appears to be able to create intraspecific physiological variations at the population level that can have a great influence on marsh plant distribution outcome.

Organisms’ survival is associated with the ability to respond to natural or anthropogenic environmental stressors. Frequently, these responses involve changes in gene regulation and expression, consequently altering physiology, development, or behavior. Here, we present modifications in response to heat exposure that mimics extreme summertime field conditions of lab-cultured and field-conditioned Nematostella vectensis. Using ATAC-seq and RNA-seq data, we found that field-conditioned animals had a more concentrated reaction to short-term thermal stress, expressed as enrichment of the DNA repair mechanism pathway. By contrast, lab animals had a more diffuse reaction that involved a larger number of differentially expressed genes and enriched pathways, including amino acid metabolism. Our results demonstrate that pre-conditioning affects the ability to respond efficiently to heat exposure in terms of both chromatin accessibility and gene expression and reinforces the importance of experimentally addressing ecological questions in the field.

Stiffness control is critical in human manipulation. The ability to transition between a low stiffness state, allowing for compliant interactions with the environment, through to rigid states, where it is possible to exert high forces, enables much functionality. Particle jamming provides an elegant method of modulating stiffness online. We develop an un-actuated anthropomorphic hand, with jamming particles enclosed in the joints surrounded by a moulded silicone skin. This approach to stiffness control also allows for control of posture, through 'pre-conditioning' by interacting with the environment in a soft state and then jamming the joints when in a new posture using a single vacuum source and control valve. To demonstrate the capabilities of this new design and fabrication approach, we introduce a 'pre-conditioning' algorithm for exploiting the soft/rigid state transition and environmental interactions to fix the hand in a given demand posture. This approach allows for accurate posture control, which translates to high grasping success rates. In conclusion, we demonstrate the advantages of the new design and fabrication approach, where jamming joints can be used to passively perform a variety of tasks through pre-conditioning of the hand posture. © 2021 IEEE.

Lipopolysacharide (LPS) pre-conditioning (PC), has been shown to exert protective effects against cytotoxic effects. Therefore, we hypothesized, the tolerance produced by LPS PC will be resulted by the alterations and modifications in gene and protein expression. With reference to the results of MTT assays, AO/PI staining, and Annexin V-FITC analyses of LPS concentration (0.7815–50 μg/mL) and time-dependent (12–72 h) experiments, the pre-exposure to 3 μg/mL LPS for 12 h protected the differentiated PC12 cells against 0.75 mg/mL LPS apoptotic concentration. LPS-treated cells secreted more inflammatory cytokines like IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-6, IL-17, IFN-γ, and TNF-α than LPS-PC cells. The production of inflammatory mediators ROS and NO was also higher in the LPS-induced cells compared to LPS-PC cells. Conversely, anti-inflammatory cytokines (like IL-10, IL-13, CNTF, and IL-1Ra) were upregulated in the LPS-PC cells but not in the LPS-induced cells. Meanwhile, the LPS initiated caspase-8 which in turn activates effector caspase 3/7. When the activities of caspases in the LPS-induced cells were inhibited using z-VADfmk and z-DEVDfmk, the expressions of c-MYC and Hsp70 were increased, but p53 was reduced. The potential molecules associated with protective and destructive effect was measured by RT2 Profiler PCR array to elucidate the signaling pathways and suggested inhibition NF-κB/caspase-3 signaling pathway regulates the cytoprotective genes and proto-oncogenes. In conclusion, this study provides a basis for future research to better understand the molecular mechanism underlying LPS pre-conditioning /TLR4 pre-activation and its functional role in offering cytoprotective response in neuronal environment.

Lipopolysacharide (LPS) pre-conditioning (PC), has been shown to exert protective effects against cytotoxic effects. Therefore, we hypothesized, the tolerance produced by LPS PC will be resulted by the alterations and modifications in gene and protein expression. With reference to the results of MTT assays, AO/PI staining, and Annexin V-FITC analyses of LPS concentration (0.7815–50 μg/mL) and time-dependent (12–72 h) experiments, the pre-exposure to 3 μg/mL LPS for 12 h protected the differentiated PC12 cells against 0.75 mg/mL LPS apoptotic concentration. LPS-treated cells secreted more inflammatory cytokines like IL-1α, IL-1β, IL-2, IL-3, IL-4, IL-6, IL-17, IFN-γ, and TNF-α than LPS-PC cells. The production of inflammatory mediators ROS and NO was also higher in the LPS-induced cells compared to LPS-PC cells. Conversely, anti-inflammatory cytokines (like IL-10, IL-13, CNTF, and IL-1Ra) were upregulated in the LPS-PC cells but not in the LPS-induced cells. Meanwhile, the LPS initiated caspase-8 which in turn activates effector caspase 3/7. When the activities of caspases in the LPS-induced cells were inhibited using z-VADfmk and z-DEVDfmk, the expressions of c-MYC and Hsp70 were increased, but p53 was reduced. The potential molecules associated with protective and destructive effect was measured by RT2 Profiler PCR array to elucidate the signaling pathways and suggested inhibition NF-κB/caspase-3 signaling pathway regulates the cytoprotective genes and proto-oncogenes. In conclusion, this study provides a basis for future research to better understand the molecular mechanism underlying LPS pre-conditioning /TLR4 pre-activation and its functional role in offering cytoprotective response in neuronal environment.

Purpose: Epigallocatechin 3-gallate (EGCG), a green tea polyphenol, has been shown to have anti-oxidant and anti-inflammatory effects in vitro and in vivo. The aim of this study was to investigate the effects and mechanism of EGCG on isolated pancreatic islets as pre-conditioning for pancreatic islet transplantation. Methods: The pancreatic islets were divided into two groups: an islet culture medium group (control) and an islet culture medium with EGCG (100 μM) group. We investigated the islet viability, Nrf2 expression, reactive oxygen species (ROS) production, and heme oxygenase-1 (HO-1) mRNA. Five hundred islet equivalents after 12 h of culture for the EGCG 100 μM and control group were transplanted under the kidney capsule of streptozotocin (STZ)-induced diabetic ICR mice. Results: The cell viability and insulin secretion ability in the EGCG group were preserved, and the nuclear translocation of Nrf2 was increased in the EGCG group (p

In the mitochondrial matrix, there are insoluble, osmotically inactive complexes that maintain a constant pH and calcium concentration. In the present paper, we examine the properties of insoluble calcium and magnesium salts, such as phosphates, carbonates and polyphosphates, which might play this role. We find that non-stoichiometric, magnesium-rich carbonated apatite, with very low crystallinity, precipitates in the matrix under physiological conditions. Precipitated salt acts as pH buffer, and, hence, can contribute in maintaining ATP production in ischemic conditions, which delays irreversible damage to heart and brain cells after stroke.

An alternative control method to the use of chemical insecticides against soil dwelling insect pests is the application of entomopathogenic nematodes formulated in alginate beads for enhanced shelf life. The aim was to compare the benefit on nematode survival and infectivity of: (i) pre-conditioning of juveniles, and (ii) coating of alginate beads. The nematodes Steinernema glaseri, Steinernema carpocapsae, and Heterorhabditis bacteriophora were reproduced in last instar larvae of the wax moth Galleria mellonella and the infective juveniles emerged were subjected to two capture treatments: white traps and plaster of Paris, the latter was utilized as a pre-conditioning treatment. A total of 1,000 infective juveniles were formulated in each sodium alginate bead with or without an alginate coating. The beads were stored at 23 ± 3°C and a bidistilled water suspension of nematodes was set as a control. The survivorship of these formulates and their infectivity on Galleria mellonella larvae were evaluated every 7 d post-formulation (dpf). In beads without pre-conditioning juveniles nor coating, Steinernema carpocapsae had the higher survival rate (58.8%), the longest survival time (28 dpf) and the higher infectivity (100%) as well. Pre-conditioning improved the survival and infectivity of Steinernema glaseri by 22.5% at 21 dpf and 70.0% at 14 dpf, respectively. Alginate coating increased survival (21.7%) and infectivity (95%) of Heterorhabditis bacteriophora for up to 28 dpf. The combination of pre-conditioning and coating slightly favored the survival (10% for up to 14 dpf) of Steinernema glaseri and infectivity (100% for up to 35 dpf) of Steinernema carpocapsae. Non pre-conditioned Steinernema carpocapsae formulated in uncoated beads was the combination with better performance in survivorship (58.8%) and infectivity (100%) at 28 dpf. It was concluded that non pre-conditioned Steinernema carpocapsae formulated in uncoated beads was the combination with better survivorship and infectivity.

Chimeric antigen receptor (CAR) T cell therapy represents a significant advancement in cancer therapy. Larger studies have shown ∼90% complete remission rates against chemoresistant and/or refractory CD19+ leukemia or lymphoma. Effective CAR T cell therapy is highly dependent on lymphodepleting preconditioning, which is achieved through chemotherapy or radiotherapy that carries with it significant toxicities. These can exclude patients of low performance status. In order to overcome the need for preconditioning, we constructed fully mouse first and second generation anti-murine CD19 CARs with or without interleukin-12 (IL-12) secretion. To test these CARs, we established a mouse model to reflect the human situation without preconditioning. Murine second generation CAR T cells expressing IL-12 were capable of eradicating established B cell lymphoma with a long-term survival rate of ∼25%. We believe this to be the first study in a truly lymphoreplete model. We provide evidence that IL-12-expressing CAR T cells not only directly kill target CD19+ cells, but also recruit host immune cells to an anti-cancer immune response. This finding is critical because lymphodepletion regimens required for the success of current CAR T cell technology eliminate host immune cells whose anti-cancer activity could otherwise be harnessed by strategies such as IL-12-secreting CAR T cells. Keywords: CD19 CAR T cells, IL-12, immunotherapy, chimeric antigen receptor, adoptive cellular therapy, lymphoma, B cell malignancies, TRUCKs, pre-conditioning

This study aimed to investigate the cardioprotection of rosuvastatin pre-conditioning (R-Pre) in a rat model of myocardial ischemia / reperfusion (I/R). Male SD rats were assigned into three groups: sham group, I/R group and R-Pre group. Rats in I/R group and R-Pre group received ischemia for 30 min and reperfusion for 2 h. In R-Pre group, rats received intragastrical administration with rosuvastatin at 5 mg/kg once daily for 1 week. After 2-h reperfusion, the cardiac function was detected by ultrasonography; the blood was collected for biochemical analysis; the heart was collected for the TUNEL staining and immunohistochemistry for Bcl-2 and Bax. Our results showed rosuvastatin pre-conditioning for 1 week could significantly reduce the infarct ratio and improve the cardiac function after myocardial I/R injury, in which attenuation of oxidative stress and cell apoptosis played an important role. Our study provides evidence on the cardioprotection of rosuvastatin pre-conditioning and highlight the use of rosuvastatin before cardiopulmonary bypass.

It has recently been revealed that during the aorta-clamped period, D-Ala2, D-Leu5-Enkephalin (DADLE) infusion can protect the spinal cord against ischemia and reperfusion (I/R) injury. However, the protective effects of DADLE administration prior to ischemia or at the time of early reperfusion have not yet been investigated. Drug pre- or post-conditioning can serve as a more valuable clinical strategy. Therefore, the present study was designed to investigate the neuroprotective effect of DADLE infusion at different time intervals in order to determine the optimum time point for ischemic spinal cord protection. A total of 40 New Zealand white rabbits were randomly divided into 5 groups: Sham-operated (Sham), normal saline pre-conditioning (NS), DADLE per-conditioning (Dper), DADLE pre-conditioning (Dpre) and DADLE post-conditioning (Dpost). All animals were subjected to spinal cord ischemia for 30 min followed by 48 h reperfusion. Hind limb motor functions were assessed according to the Tarlov criterion when the animals regained consciousness, 6, 24 and 48 h after reperfusion. Histological analysis and the number of viable α-motor neurons were also used to assess the extent of spinal cord injury. Compared with the NS group, the Tarlov scores and the number of normal neurons were significantly higher in the Dper group (P

The risk for decompression sickness (DCS) after hyperbaric exposures (such as SCUBA diving) has been linked to the presence and quantity of vascular gas emboli (VGE) after surfacing from the dive. These VGE can be semi-quantified by ultrasound Doppler and quantified via precordial echocardiography. However, for an identical dive, VGE monitoring of divers shows variations related to individual susceptibility, and, for a same diver, dive-to-dive variations which may be influenced by pre-dive pre-conditioning. These variations are not explained by currently used algorithms. In this paper, we present a new hypothesis: individual metabolic processes, through the oxygen window (OW) or Inherent Unsaturation of tissues, modulate the presence and volume of static metabolic bubbles (SMB) that in turn act as precursors of circulating VGE after a dive., info:eu-repo/semantics/published

Helium has been classified as a kind of inert gas that is not effortless to spark chemical reactions with other substances in the past decades. Nevertheless, the cognition of scientists has gradually changed accompanied with a variety of studies revealing the potential molecular mechanism underlying organ-protection induced by helium. Especially, as a non-anesthetic gas which is deficient of relevant cardiopulmonary side effects, helium conditioning is recognized as an emerging and promising approach to exert favorable effects by mimicking the cardioprotection of anesthetic gases or xenon. In this review we will summarize advances in the underlying biological mechanisms and clinical applicability with regards to the cardioprotective effects of helium.

Isoflurane, a volatile and inhalational anesthetic, has been extensively used in perioperative period for several decades. A large amount of experimental studies have indicated that isoflurane exhibits neuroprotective properties when it is administrated before or after (pre-conditioning and post-conditioning) neurodegenerative diseases (e.g., hypoxic ischemia, stroke and trauma). Multiple mechanisms are involved in isoflurane induced neuroprotection, including activation of glycine and γ-aminobutyric acid receptors, antagonism of ionic channels and alteration of the function and activity of other cellular proteins. Although neuroprotection provided by isoflurane is observed in many animal studies, convincing evidence is lacking in human trials. Therefore, there is still a long way to go before translating its neuroprotective properties into clinical practice.

Generalist herbivores can face many challenges when choosing their host plant. This can be particularly difficult if their choice and performance are affected by host experience. Greenhouse whitefly, Trialeurodes vaporariorum Westwood (Hemiptera: Aleyrodidae), is an invasive generalist herbivore, which has established in year-round greenhouses at northern latitudes where it cannot overwinter outdoors. It mainly uses crops such as cucumber (Cucumis sativus L.), tomato (Solanum lycopersicum L.), and ornamentals as host plants. However, every summer the insect escapes greenhouses and is exposed to natural vegetation. We evaluated the performance of T. vaporariorum on diverse vegetation outside greenhouses after prolonged experience of greenhouse crops. First, we surveyed the vegetation near infested greenhouses. Development success of the insect differed among wild hosts. We identified five new hosts among 12 plant species that bore pupae and were thus considered suitable as the insect's host plants. Members of the Urticaceae and Onagraceae were the most preferred and frequently inhabited by all insect life stages. The highest abundance of insects occurred in plots with low plant species richness, independent of plant family in these habitats. We then studied experimentally the impact of 1 year of preconditioning to one of three common greenhouse crops, cucumber, tomato, or poinsettia (Euphorbia pulcherrima Willd. ex Klotzsch), on the performance of the preconditioned adults and their progeny on four wild plants. Adults from tomato and poinsettia preferred the novel host species over the species to which they were preconditioned. The whitefly population preconditioned to cucumber was the most fecund on all offered hosts. We conclude that generalist herbivores can have large variation in performance, despite polyphagy, on novel hosts as shown by the variable abundance of T. vaporariorum pupae among outdoor hosts. Furthermore, performance of whiteflies on natural vegetation was affected by experience on greenhouse crops. Based on our observations, we provide insights and recommendations for pest management.

Background: To evaluate the effect of anaesthesia and ICU sedation with sevoflurane to protect the myocardium against ischemia-reperfusion injury associated to cardiac surgery assessed by troponin release. Methods: We performed a prospective, open-label, randomized study in cardiac surgery with cardiopulmonary bypass. Patients were randomized to an algorithm-based intervention group and a control group. The main outcome was the perioperative kinetic of cardiac troponin I (cTnI). The secondary outcomes included composite endpoint, GDF-15 (macrophage inhibitory cytokine-1) value, arterial lactate levels, and the length of stay (LOS) in the ICU. Results: Of 82 included patients, 81 were analyzed on an intention-to-treat basis (intervention group: n = 42; control group: n = 39). On inclusion, the intervention and control groups did not differ significantly in terms of demographic and surgical data. The postoperative kinetics of cTnI did not differ significantly between groups: the mean difference was 0.44 ± 1.09 μg/ml, P = .69. Incidence of composite endpoint and GDF-15 values were higher in the sevoflurane group than in propofol group. The intervention and control groups did not differ significantly in terms of ICU stay and hospital stay. Conclusion: The use of an anaesthesia and ICU sedation with sevoflurane was not associated with a lower incidence of myocardial injury assessed by cTnI. Sevoflurane administration was associated with higher prevalence of acute renal failure and higher GDF-15 values.

Apesar da importância económica do gergelim é necessário ainda obter informações mais precisas e completas sobre a qualidade fisiológica de suas sementes. Considerando que o teste de tetrazólio permite avaliar eficientemente e com rapidez o potencial fisiológico das sementes, o objetivo deste estudo consistiu em adequar a metodologia deste teste para sementes de gergelim. Sementes de gergelim das cultivares ‘BRS G2’, ‘BRS Seda’, ‘Seridó’ e ‘BRS G4’ foram submetidas à pré-testes para determinar o tempo de pré-condicionamento das sementes intactas, sementes com cortes na região distal ao eixo embrionário ou corte longitudinal no maior sentido da semente, durante 30, 60 e 90 minutos em água. Após definir o pré-condicionamento por 60 minutos, com corte longitudinal no maior sentido, as sementes foram imersas nas concentrações de 0,075%; 0,5% e 1,0% de solução de tetrazólio a 30 ºC durante 3; 6; 8; 12; 18 e 24-h. A embebição das sementes sobre papel durante 60 minutos, seguida de corte longitudinal e imersão em solução de tetrazólio na concentração de 0,075% por 12-h e 1,0% por 3-h foram eficientes na avaliação da viabilidade das sementes de gergelim., Revista de Ciências Agrárias, vol. 38 n.º 3 (2015)

Plant growth-promoting bacterial endophytes or PGPBE are considered the future of plants growth bio-stimulators, based on their undeniable advantageous over epiphytic microorganism commonly applied to enhance host plant nutrition and protection. However, current research of these plant-associated microorganisms has deficiencies concerning cultivation and pre-formulation strategies on further bioactivity as an endophyte. Besides, the repercussion of cultivation conditions and osmotic stress in PGPBE on P-solubilizing ability has not been yet addressed. Through the strategy by pre-conditioning of cells with osmoadaptation, hydroxyectoine accumulation and a further encapsulation of cells in amidated pectin beads, this doctoral research aimed at enhancing the capacity of the PGPBE Kosakonia radicincitans DSM16656T strain to colonize plant seedlings, solubilize phosphate and support the drying survival during formulation processing. Here, it was demonstrated that halotolerant phenotypes of bacteria provide a remarkable positive influence on drying survival and about 3-fold increased the plant endosphere colonization capacity, supporting growth promotion effects in radish plants up to 41.1 % in the fresh matter. Interestingly, the pre-conditioning lead to an increase of 23.3 % in the in vitro phosphate solubilization ability by positively affecting acid phosphatases production. Beyond the accumulation of hydroxyectoine, this work provides evidence supporting the notion that hydroxyectoine can produce significant changes in the endogenous metabolome of K. radicincitans DSM16656T during the exponential growth phase at high salinities. Metabolome changes include alterations on tricarboxylic acid cycle, novo-synthesis of specific intracellular metabolites such as mannitol, myo-inositol and trehalose, and up-regulation on amino acids such as L-leucine, L-asparagine, L-serine, L-methionine and L-proline. The significant 11.07-fold change of L-aspartate suggests a potential acidic proteome at high salinities, extending the knowledge of traits for salt-stressed bacterial endophytes. Likewise, pre-osmoadapted bacteria formulated in amidated hydrogel pectin dried beads, 10-fold increased the ability to multiply endophytically and the efficacy as a plant growth promoter in radish plants. GFP-tagged bacteria approach revealed that bacterial aggregates formed during the re-hydration of beads play an essential role in early colonization stages. Overall, these findings place the metabolic salt stress response and the hydroxyectoine accumulation by K. radicincitans DSM16656T into a physiological context, paving the way into the interaction between the cellular phenotype associated with salt stress tolerance, and drying survival capacity of Gram-negative endophytes. This investigation provides insights for understanding the success of pre-conditioned and immobilized bacterial endophytes, also their mechanisms during early plant colonization establishments, encouraging the integration of fermentation and formulation strategies for exploiting endophytic bacteria. Los endófitos bacterianos que promueven el crecimiento de las plantas o PGPBE se consideran el futuro de los bioestimulantes en plantas, con base en su innegable ventaja sobre los microorganismos epífitos que se aplican comúnmente para mejorar la nutrición y protección. Sin embargo, la investigación actual de estos microorganismos asociados a las plantas tiene deficiencias en relación con la influencia de las estrategias de cultivo y de pre-formulación con la subsecuente capacidad de colonización de plantas. Además, todavía no se ha abordado la influencia de las condiciones de cultivo y el estrés osmótico en PGPBE sobre la capacidad de solubilización de fósforo. Esta investigación doctoral tuvo como objetivo mejorar la capacidad de la cepa PGPBE Kosakonia radicincitans DSM 16656T para colonizar plantas, solubilizar fosfato y favorecer la supervivencia al secado durante la formulación. La estrategia incluye el pre-acondicionamiento de las células con osmo-adaptación, acumulación de hidroxiectoina y posterior encapsulación de las células utilizando pectina amidada. Los resultados demostraron que los fenotipos halotolerantes de las bacterias proporcionan una notable influencia positiva en la supervivencia al secado y aumentan aproximadamente en 3 veces la capacidad de colonización de la raíz, lo que respalda los efectos de la promoción del crecimiento en plantas de rábano hasta de 41,1% en la materia fresca. Es así como, el pre-acondicionamiento condujo a un aumento del 23,1% en la capacidad de solubilización de fosfato in vitro al afectar positivamente la producción de fosfatasas ácidas. Más allá de la acumulación de hydroxiectoina, este trabajo proporciona evidencia que apoya la noción de que la hydroxiectoina puede producir cambios significativos en el metaboloma endógeno de K. radicincitans DSM 16656T durante la fase de crecimiento exponencial en salinidades altas. Los cambios metabólicos incluyen alteraciones en el ciclo del ácido tricarboxílico, novo-síntesis de metabolitos intracelulares específicos como manitol, mio-inositol y trehalosa, y cambios en los aminoácidos como L-leucina, L-asparagina, L-serina, L-metionina y L-prolina. El significativo cambio de 11,07 veces de L-aspartato sugiere un potencial proteoma ácido en salinidades altas, lo que amplía el conocimiento de las bacterias endófitas bajo estrés salino. Además, las bacterias pre-osmoadaptadas formuladas en capsulas secas de pectina amidada aumentaron en 10 veces la capacidad endofítica y la eficacia como promotor del crecimiento de plantas de rábano bajo condiciones de invernadero. También, los agregados bacterianos formados durante la activación de las capsulas juegan un papel esencial en las etapas tempranas de colonización. Estos hallazgos ubican la respuesta metabólica al estrés salino y la acumulación de hidroxiectoina por K. radicincitans DSM 16656T en un contexto fisiológico, allanando el camino hacia la interacción entre el fenotipo celular asociado con la tolerancia al estrés salino y la capacidad de supervivencia de los endófitos Gram-negativos. Por último, esta investigación proporciona información para comprender el éxito de los endófitos bacterianos pre-acondicionados e inmovilizados, asi como sus mecanismos durante los primeros establecimientos de colonización de plantas, alentando la integración de las estrategias de fermentación y formulación para explotar las bacterias endofíticas. Doctor en Ingeniería Química. Línea de Investigación: Bioprocesos. Doctorado

Mesenchymal stromal cells (MSCs) are self-renewing, culture-expandable adult stem cells that have been isolated from a variety of tissues, and possess multipotent differentiation capacity, immunomodulatory properties, and are relatively non-immunogenic. Due to this unique set of characteristics, these cells have attracted great interest in the field of regenerative medicine and have been shown to possess pronounced therapeutic potential in many different pathologies. MSCs' mode of action involves a strong paracrine component resulting from the high levels of bioactive molecules they secrete in response to the local microenvironment. For this reason, MSCs' secretome is currently being explored in several clinical contexts, either using MSC-conditioned media (CM) or purified MSC-derived extracellular vesicles (EVs) to modulate tissue response to a wide array of injuries. Rather than being a constant mixture of molecular factors, MSCs' secretome is known to be dependent on the diverse stimuli present in the microenvironment that MSCs encounter. As such, the composition of the MSCs' secretome can be modulated by preconditioning the MSCs during in vitro culture. This manuscript reviews the existent literature on how preconditioning of MSCs affects the therapeutic potential of their secretome, focusing on MSCs' immunomodulatory and regenerative features, thereby providing new insights for the therapeutic use of MSCs' secretome. We would like to acknowledge Norte Portugal Regional Operational Programme (NORTE 2020) in the framework of the project “Bioengineered Therapies for Infectious Diseases and Tissue Regeneration” (NORTE-01-0145-FEDER-000012). We also acknowledge Fundação para a Ciência e a Tecnologia (FCT) and Fundo Europeu de Desenvolvimento Regional (FEDER) funds through the COMPETE 2020-Operacional Programme for Competitiveness and Internationalization (POCI), Portugal 2020-in the framework of the project “Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274). We also acknowledge EUROSPINE TRF for the funded project “Disc Regeneration, Immuno, and Neuro Modulation” , ref. 2017_05 . In addition, JF and RG also acknowledge FCT for funding the BiotechHealth Ph.D. fellowship (PD/BD/135486/2018) and the FCT Investigator Grant (IF/00638/2014), respectively.

Objective The purpose of this study was to evaluate potential relationships between cytokine gene expression, complete blood counts (CBC) and animals that were sick or would become sick. The CBC and the transcript abundance of cytokines and their receptors expressed in leukocytes were measured from calves at two early timepoints, and again after diagnosis with bovine respiratory disease (BRD). Results Blood was collected from calves at pre-conditioning (n = 796) and weaning (n = 791) for CBC. Blood counts were also measured for the calves with BRD (n = 13), and asymptomatic calves (n = 75) after weaning. The CBC were compared for these animals at 3 time points. At diagnosis, neutrophils were higher and basophils lower in sick animals (P

The astonishing clinical success of CD19 chimeric antigen receptor (CAR) T-cell therapy has led to the approval of two second generationchimeric antigen receptors (CARs) for acute lymphoblastic leukemia (ALL) andnon-Hodgkin lymphoma (NHL). The focus of the field is nowon emulating these successes in other hematological malignancies where less impressive complete response rates are observed. Furtherengineering of CAR T cells or co-administration of other treatment modalities may successfully overcome obstacles to successful therapy inother cancer settings.We therefore present a model in which others can conduct pre-clinical testing of CD19 CAR T cells. Results in this well tested B-cell lymphomamodel are likely to be informative CAR T-cell therapy in general.This protocol allows the reproducible production of mouse CAR T cells through calcium phosphate transfection of Plat-E producer cells withMP71 retroviral constructs and pCL-Eco packaging plasmid followed by collection of secreted retroviral particles and transduction usingrecombinant human fibronectin fragment and centrifugation. Validation of retroviral transduction, and confirmation of the ability of CAR T cellsto kill target lymphoma cells ex vivo, through the use of flow cytometry, luminometry and enzyme-linked immunosorbent assay (ELISA), is alsodescribed.Protocols for testing CAR T cells in vivo in lymphoreplete and lymphodepleted syngeneic mice, bearing established, systemic lymphoma aredescribed. Anti-cancer activity is monitored by in vivo bioluminescence and disease progression. We show typical results of eradication ofestablished B-cell lymphoma when utilizing 1st or 2nd generation CARs in combination with lymphodepleting pre-conditioning and a minority ofmice achieving long term remissions when utilizing CAR T cells expressing IL-12 in lymphoreplete mice.These protocols can be used to evaluate CD19 CAR T cells with different additional modification, combinations of CAR T cells and othertherapeutic agents or adapted for the use of CAR T cells against different target antigens.

In the CNS short episodes of acute hypoxia can result in a decrease in synaptic transmission which may be fully reversible upon re-oxygenation. Stabilization of hypoxia-inducible factor (HIF) by inhibition of prolyl hydroxylase domain (PHD) enzymes has been shown to regulate the cellular response to hypoxia and confer neuroprotection both in vivo and in vitro. Hypoxic preconditioning has become a novel therapeutic target to induce neuroprotection during hypoxic insults. However, there is little understanding of the effects of repeated hypoxic insults or pharmacological PHD inhibition on synaptic signalling. In this study we have assessed the effects of hypoxic exposure and PHD inhibition on synaptic transmission in the rat CA1 hippocampus. Field excitatory postsynaptic potentials (fEPSPs) were elicited by stimulation of the Schaffer collatoral pathway. 30 min hypoxia (gas mixture 95% N2/5% CO2) resulted in a significant and fully reversible decrease in fEPSP slope associated with decreases in partial pressures of tissue oxygen. 15-30 min of hypoxia was sufficient to induce stabilization of HIF in hippocampal slices. Exposure to a second hypoxic insult after 60 min resulted in a similar depression of fEPSP slope but with a significantly greater rate of recovery of the fEPSP. Prior single treatment of slices with the PHD inhibitor, dimethyloxalylglycine (DMOG) also resulted in a significantly greater rate of recovery of fEPSP post hypoxia. These results suggest that hypoxia and ‘pseudohypoxia’ preconditioning may improve the rate of recovery of hippocampal neurons to a subsequent acute hypoxia. University College Dublin Science Foundation Ireland (SFI)

The chloride contamination will occur from the application of de-icing salts. It was confirmed that the application of de-icing salts caused a significant reduction in structural and serviceability reliabilities. The chemicals used in the snow and ice control operations (de-icers) may cause corrosion damage to the transportation infrastructure such as reinforced/pre-stressed concrete structures and steel bridges. There are many ways to manage the corrosive effects of de-icers, such as selection of high-quality concrete, adequate ANALYSIS VOL. 4, 2018 ISSN 2394–3750 EISSN 2394–3769 SCIENCE TECHNOLOGY & © 2018 Discovery Publication. All Rights Reserved. www.discoveryjournals.org OPEN ACCESS Page 147 ANALYSIS ARTICLE concrete cover and alternative reinforcement, control of the ingress and accumulation of deleterious species, injection of beneficial species into concrete, and use of non-corrosive de-icer alternatives and optimal application rates. In fact, snow and ice on streets and highways are a major threat to human life and limb. Traffic accidents and fatalities climb as snow and ice reduce traction on roadways. Lengthened emergency response times create additional risks for persons in urgent need of medical care, particularly in cases of heart attacks, burns, childbirth and poisoning. Thus the de-icing salts are necessary to provide safe winter driving conditions and save lives by preventing the freezing of a layer of ice on concrete infrastructure. However, the safety and sense of comfort provided by these salts is not without a price, as these salts can greatly contribute to the degradation and decay of reinforced concrete transportation systems. The importance of chloride concentration as a durability-based material property has received greater attention only after the revelation that chloride-induced corrosion is the major problem for concrete durability. Therefore, there is a need to quantify the chloride concentration in concrete which is of paramount importance. The present research work was made an attempt to interpret the concrete chloride absorption in ordered to characterize the different concrete mixtures design for in case of pre-conditioned concrete cubes such as dry/fully/partially saturated condition and salt ponded with chloride solution for about 160 days. Thus the objectives of this present research are such as: First, this research will examine the influence of conditioning such as dry/fully/partially saturated condition on the results of chloride concentration performed on concrete cubes with different mixtures proportion in which slump, and w/c ratio value was varied with constant compressive strength as in the First case and compressive strength, and w/c ratio value varied with constant slump as in the Second case. Seventy-two concrete cubes (100 mm3) with Grades of concrete ranges from 25 to 40 N/mm2 were prepared and evaluate the chloride absorption under different exposure condition. It’s concluded from the results that, in dry/saturated conditioned concrete cubes, the chloride absorption value was increased in all designed mixtures type. Similarly, the average chloride concentration was decreased in solvent based and water based impregnation DCC/PSC/FSC cubes as when compared to control DCC/PSC/FSC cubes for constant higher compressive strength and varied slump value as well as varied compressive strength and constant slump value. Whereas the average chloride absorption was increased in solvent based and water based impregnation DCC/PSC/FSC cubes for lesser compressive strength and constant slump value as when compared to constant higher compressive strength and varied slump value and the chloride concentration was going on decreases with increased compressive strength and constant slump value.

Irreversible myocardial damage happens in the presence of prolonged and severe ischemia. Several phenomena protect the heart against myocardial infarction and other adverse outcomes of ischemia and reperfusion (IR), namely: hibernation related to stunned myocardium, ischemic preconditioning (IPC), ischemic post-conditioning, and their pharmacological surrogates. Ischemic preconditioning consists in the induction of a brief IR to reduce damage of the tissue caused by prolonged and severe ischemia. Nitric oxide (NO) signaling plays an essential role in IPC. Nitric oxide-sensitive guanylate cyclase/cyclic guanosine-3′,5′-monophosphate (cGMP)-dependent protein kinase type I-signaling pathway protects against the IR injury during myocardial infarction. Mitochondrial ATP-sensitive and Ca2+-activated K+ channels are involved in NO-mediated signaling in IPC. Independently of the cGMP-mediated induction of NO production, S-nitrosation represents a regulatory molecular mechanism similar to phosphorylation and is essential for IPC. Unlike conditioning phenomena, the mechanistic basis of myocardial stunning and hibernation remains poorly understood. In this review article, we hypothesize that the disruption of electrical syncytium of the myocardium may underly myocardial stunning and hibernation. Considering that the connexins are the building blocks of gap junctions which represent primary structural basis of electrical syncytium, we discuss data on the involvement of connexins into myocardial conditioning, stunning, and hibernation. We also show how NO-mediated signaling is involved in myocardial stunning and hibernation. Connexins represent an essential element of adaptation phenomena of the heart at the level of both the cardio- myocytes and the mitochondria. Nitric oxide targets mitochondrial connexins which may affect electrical syncytium continuum in the heart. Mitochondrial connexins may play an essential role in NO-dependent mechanisms of myocardial adaptation to ischemia.

A new era of plant biochemistry at the systems level is emerging, providing detailed descriptions of biochemical phenomena at the cellular and organismal level. This new era is marked by the advent of metabolomics—the qualitative and quantitative investigation of the entire metabolome (in a dynamic equilibrium) of a biological system. This field has developed as an indispensable methodological approach to study cellular biochemistry at a global level. For protection and survival in a constantly-changing environment, plants rely on a complex and multi-layered innate immune system. This involves surveillance of ‘self’ and ‘non-self,’ molecule-based systemic signalling and metabolic adaptations involving primary and secondary metabolites as well as epigenetic modulation mechanisms. Establishment of a pre-conditioned or primed state can sensitise or enhance aspects of innate immunity for faster and stronger responses. Comprehensive elucidation of the molecular and biochemical processes associated with the phenotypic defence state is vital for a better understanding of the molecular mechanisms that define the metabolism of plant–pathogen interactions. Such insights are essential for translational research and applications. Thus, this review highlights the prospects of metabolomics and addresses current challenges that hinder the realisation of the full potential of the field. Such limitations include partial coverage of the metabolome and maximising the value of metabolomics data (extraction of information and interpretation). Furthermore, the review points out key features that characterise both the plant innate immune system and enhancement of the latter, thus underlining insights from metabolomic studies in plant priming. Future perspectives in this inspiring area are included, with the aim of stimulating further studies leading to a better understanding of plant immunity at the metabolome level.

Acute brain injury is a critical and emergent condition in clinical settings, which needs to be addressed urgently. Commonly acute brain injuries include traumatic brain injury, ischemic and hemorrhagic strokes. Oxidative stress is a key contributor to the subsequent injuries and impedes the reparative process after acute brain injury; therefore, facilitating an anti-oxidative approach is important in the care of those diseases. Readiness to deliver and permeability to blood brain barrier are essential for the use of this purpose. Inhaled anesthetic gases are a group of such agents. In this article, we discuss the anti-oxidative roles of anesthetic gases against acute brain injury.

The aim of the present study was to explore the roles and possible molecular mechanism of the alleviating effect of sevoflurane pre‑treatment on the extracorporeal circulation and to investigate the possible involvement of the Toll‑like receptor (TLR3) signaling pathway. A total of 64 male Sprague Dawley rats were randomly divided into three groups: The sham operation group (H group; n=8), cardiopulmonary bypass (CPB) group (C group; n=24) and sevoflurane pre‑conditioning group (S group; n=32). The C group was subjected to tracheal intubation and mechanical ventilation, vessel puncture and catheter placement in the right femoral artery and right internal jugular vein, while no CPB was performed in the H group. The S group was pre‑treated with 2.4% sevoflurane for 1 h prior to establishing the CPB model. The CPB in the C and S groups was performed for 1 h. Blood of the rats was analyzed and clinical parameters were detected prior to, during and at various time‑points after CPB. In addition, eight rats from the C and S groups each were sacrificed at these time‑points and brain tissue samples were analyzed. The levels of the brain damage‑specific protein S100‑β as well as IL‑6 and IFN‑β in the serum were detected by ELISA; furthermore, the expression levels of TLR3 and TIR‑domain‑containing adapter‑inducing interferon‑β (TRIF) in the left hippocampus were assessed by ELISA and/or western blot analysis. The right hippocampus was assessed for neuronal apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The mean arterial pressure, heart rate and hematocrit were significantly decreased following CPB (P

The tetrazolium test is considered a promising alternative for quick evaluation of viability and vigor of seeds. The adequatio of tetrazolium test methodology for crambe seeds, specie that presents high potential for biodiesel production, may accelerate the determination of quality of different lots. With the aim to verify the ideal conditions for the tetrazolium test for crambe seeds, five lots of cultivar FMS Brilhante were submitted to the imbibition between paper in water at 30°C for three hours and after the longitudinal slicing, seeds were soaked in tetrazolium solution at concentrations of 0.075%; 0.5% and 1.0% at 30°C for 18 h and 24 h. It was observed that in the concentration of 0.75% seeds got an adequate coloration and with 0.5% and 1.0% the coloration was too intense. The imbibition of seeds between paper for 3 hours, followed by the longitudinal slicing and the utilization of 0.075% concentration for 18h or 24 hours was efficient to the evaluation of viability of crambe seeds.

Unexpected cardiac adverse effects are the leading causes of discontinuation of clinical trials and withdrawal of drugs from the market. Since the original observations in the mid-90s, it has been well established that cardiovascular risk factors and comorbidities (such as ageing, hyperlipidaemia, and diabetes) and their medications (e.g. nitrate tolerance, adenosine triphosphate-dependent potassium inhibitor antidiabetic drugs, statins, etc.) may interfere with cardiac ischaemic tolerance and endogenous cardioprotective signalling pathways. Indeed drugs may exert unwanted effects on the diseased and treated heart that is hidden in the healthy myocardium. Hidden cardiotoxic effects may be due to (i) drug-induced enhancement of deleterious signalling due to ischaemia/reperfusion injury and/or the presence of risk factors and/or (ii) inhibition of cardioprotective survival signalling pathways, both of which may lead to ischaemia-related cell death and/or pro-arrhythmic effects. This led to a novel concept of ‘hidden cardiotoxicity’, defined as cardiotoxity of a drug that manifests only in the diseased heart with e.g. ischaemia/reperfusion injury and/or in the presence of its major comorbidities. Little is known on the mechanism of hidden cardiotoxocity, moreover, hidden cardiotoxicity cannot be revealed by the routinely used non-clinical cardiac safety testing methods on healthy animals or tissues. Therefore, here, we emphasize the need for development of novel cardiac safety testing platform involving combined experimental models of cardiac diseases (especially myocardial ischaemia/reperfusion and ischaemic conditioning) in the presence and absence of major cardiovascular comorbidities and/or cotreatments.

We previously demonstrated that pre‐conditioning with CpG oligonucleotide (ODN) 1668 induces quick up‐regulation of gene expression 3 hours post‐murine myocardial ischaemia/reperfusion (I/R) injury, terminating inflammatory processes that sustain I/R injury. Now, performing comprehensive microarray and biocomputational analyses, we sought to further enlighten the “black box” beyond these first 3 hours. C57BL/6 mice were pretreated with either CpG 1668 or with control ODN 1612, respectively. Sixteen hours later, myocardial ischaemia was induced for 1 hour in a closed‐chest model, followed by reperfusion for 24 hours. RNA was extracted from hearts, and labelled cDNA was hybridized to gene microarrays. Data analysis was performed with BRB ArrayTools and Ingenuity Pathway Analysis. Functional groups mediating restoration of cellular integrity were among the top up‐regulated categories. Genes known to influence cardiomyocyte survival were strongly induced 24 hours post‐I/R. In contrast, proinflammatory pathways were down‐regulated. Interleukin‐10, an upstream regulator, suppressed specifically selected proinflammatory target genes at 24 hours compared to 3 hours post‐I/R. The IL1 complex is supposed to be one regulator of a network increasing cardiovascular angiogenesis. The up‐regulation of numerous protective pathways and the suppression of proinflammatory activity are supposed to be the genetic correlate of the cardioprotective effects of CpG 1668 pre‐conditioning.

Giriş ve Amaç: Son yıllarda otolog yağ grefti uygulamaları, rekonstrüktif ve estetik cerrahide sıkça kullanılmaktadır. Yağ grefti uygulamasının ana avantajları; kolay uygulanabilir olması, tekrarlanabilir olması, hastanın mevcut dokularının kullanılması ve uygulanan hastaya göre istenilen miktarda elde edilebilir olmasıdır. Yağ grefti sağ kalım oranlarının yüzde 20 ile 90 arasında değişim göstermesi ve bu sağ kalımın ön görülemez olması ise en önemli dezavantajıdır (Ersek, 1991) (Goldwyn, 1988).Botulinium toksin enjeksiyonları, yüz germe efekti (Kashkouli, Amani, Jamshidian-Tehrani, Yousefi, & Jazayeri, 2014), skar dokusunu azaltma (Xiao, Zhang, Liu, & Ren, 2011) ve flep sağkalımını artırma (Chenwang et al., 2009) gibi geniş yelpazede klinik uygulamalarda kullanılmaktadır. Deri fleplerinde botulinium toksin-A'nın sempatik nöronları baskılaması sonucunda vazodilatasyon yapması ile flebin kan akımını ve yaşayabilirliğini arttırabileceğini, bunu da VEGF ve CD31 gibi mediyatörlerin salınımını artırması ile gerçekleştirdiğini belirten çalışmalar literatürde mevcuttur (Kim et al., 2009).Bu çalışmanın amacı; sıçanlarda botulinium toksin-A ile denerve edilmiş ve damarlanması artmış alanlardan 'alınan' veya böyle alanlara 'verilen' yağ greftinin sağ kalımına etkisinin hem alıcı hem de verici alan üzerinden değerlendirmektir. Gereç ve Yöntem:Bu çalışma çift kör randomize bir çalışma olarak tasarlanmıştır. Araştırmamızda 40 adet Wistar cinsi sıçanlar randomize olarak 5 gruba ayrılmıştır. Tüm gruplarda yağ grefti verici alan olarak sağ inguinal yağ yastıkçığı ve alıcı alan olarak interskapular bölgedeki dorsal subkutan saha kullanılmıştır. Kontrol grubu dışındaki enjeksiyonlar, gruplara uygun olarak belirtilen bölgelere uygulanmıştır.Kontrol grubunda (grup 1); yağ grefti, sağ inguinal bölgeye insizyon ile girilip yağ yastıkçığı şeklinde alınmıştır. Verici alanın primer sütüre edilmesinin ardından, alınan yağ grefti serum fizyolojik ile yıkanıp, dorsal subkutan bölgeye kesi ile girilmiş ve burada standart olarak açılan alana yerleştirilmiştir. İkinci grupta; sağ inguinal bölgeye 1.5 Ü (0,75 cc serum fizyolojik içerisinde) botulinium toksin A (BTx- A) enjeksiyonu uygulanıp, 7 gün sonra aynı işlem ile alınan yağ grefti dorsal subkutan bölgeye aynı işlem ile yerleştirilmiştir. Üçüncü grupta; sağ inguinal bölgeye 0,75 cc serum fizyolojik enjeksiyonu uygulanıp, 7 gün sonra aynı işlem ile alınan yağ grefti dorsal subkutan bölgeye aynı işlem ile yerleştirilmiştir.Dördüncü grupta; dorsal subkutan bölgeye 1.5 Ü BTx- A (0,75 cc serum fizyolojik içerisinde) uygulanıp; yedi gün sonra, sağ inguinal bölgeden alınan yağ grefti ön koşullandırılan dorsal subkutan bölgeye aynı işlem ile yerleştirilmiştir. Beşinci grupta ise; dorsal subkutan bölgeye 0.75 cc serum fizyolojik uygulanıp; 7 gün sonra, sağ inguinal bölgeden alınan yağ greftinin, daha önce enjeksiyon yapılan dorsal subkutan bölgeye aynı işlem ile yerleştirilmiştir.Beş gruptaki dorsal bölgeye yerleştirilmiş olan yağ greftleri sekiz haftanın sonunda ağırlık ve hacim kaybı açısından, apoptotik hücre varlığı açısından ve histopatolojik olarak da beş kriter altında (kist oluşumu, inflamasyon, anjiyogenez, hasarlı uniloküler yağ doku varlığı ve multiloküler yağ doku oluşumu) incelenmiştir.Her bir grubun kendi içerisindeki ağırlık ve hacim değişim verileri 'Wilcoxon matched pairs signed rank test' ile değerlendirilmiştir. Beş grubun biribiri ile histolojik parametrelerin değerlendirilmesinde 'Kruskal-Wallis (non-parametrik ANOVA) testi' kullanılmıştır. Bu testte değerlerin anlamlı bulunması durumunda ise 'Dunn çoklu karşılaştırma testi' ile gruplar ikili olarak karşılaştırılmıştır.Bulgular: Yağ greftlerindeki ağırlık ve hacim kaybı açısından gruplar arasında anlamlı bir farkın olmadığı tespit edildi (p >0,05). Ancak dorsal alıcı alana botulinum toksin-A (BTx- A) enjeksiyonu uygulanan dördüncü gruptaki yağ grefti ağırlık kaybının en az olduğu, kontrol grubu olan birinci gruptaki yağ grefti ağırlık kaybının ise en fazla olduğu tespit edildi. Beş grup arasında; kist oluşumu, inflamasyon derecesi, apoptotik hücre varlığı ve anjiyogenez açısından anlamlı bir farkın olmadığı tespit edildi (p > 0,05). İnguinal ve dorsal bölgenin BTx-A ile ön koşullandırıldığı iki gruptaki anjiogenez skorlamasının diğer gruplara göre göreceli olarak artmış olduğu saptandı. Hasarlı uniloküler yağ doku varlığı açısından gruplar değerlendirildiğinde; verici alana (inguinal bölgeye) BTx-A enjeksiyonu yapılan grupta (grup 2), hasarlı doku oranının istatistiksel olarak anlamlı derecede azalmış olduğu tespit edildi (p: 0.0023). Multiloküler yağ doku oluşumu açısından gruplar değerlendirildiğinde ise; alıcı alana BTx-A enjeksiyonu yapılan grupta (grup 4), yeni yağ doku oluşumunun istatistiksel olarak anlamlı derecede artmış olduğu tespit edildi (p: 0.0016). Tartışma ve Sonuç: Botulinum toksin-A ile birlikte yağ grefti işlemi plastik ve rekonstrüktif cerrahide yaygın olarak kullanılmaktadır. Bununla birlikte, bu kombine kullanım halen tartışmalıdır. Baek ve arkadaşlarının yaptıkları bir çalışmada, BTx-A ile karıştırılarak verilen yağ greftlerindeki hücresel bütünlüğün, yağ grefti ağırlığının ve hacminin istatistiksel olarak anlamlı derecede artmış olduğu, bununda alıcı alandaki kas kasılmasının BTx-A ile azalmasına bağlı olabileceği savunulmuştur (Baek et al., 2012). Bizim çalışmamızda, alıcı alandaki kas kasılmasına BTx-A ile müdahale edilmeksizin verici alana uygulanan BTx-A grubunda hasarlı yağ dokularının anlamlı derecede daha az olduğu ortaya konulmuştur. Elde edilen bu sonuç ise, BTx-A'nın yağ grefti üzerine etkisinin sadece kas kasılmasını engelleyerek etki etmediği şeklinde yorumlanabilir.Tang ve arkadaşlarının yaptıkları deneysel bir çalışmada ise botulinum toksin-A ile karıştırılarak verilen yağ greftlerinde CD31 ve VEGF ekspresyon düzeyinin istatistiksel olarak arttığı saptanmıştır (Tang et al., 2017). Bizim çalışmamızda ise BTx-A'nın etkinliği dokular üzerine ön koşullandırma yapılarak ve verici alan üzerindeki etkisi de araştırmaya alınarak yağ grefti sağ kalıma etkisi incelenmiştir.Sonuç olarak bizim çalışmamızda alıcı ve verici saha BTx-A ile ön koşullandırılmasının ardından yağ grefti sağ kalımı araştırılmıştır. Verici alanın BTx-A ile ön koşullandırıldığı yağ greftlerinde hasarlı yağ doku oranın istatistiksel olarak anlamlı derecede azalmış olduğu, alıcı alanın BTx-A ile ön koşullandırıldığı yağ greftlerinde ise yağ greftindeki yeni multiloküler yağ oranın istatistiksel olarak anlamlı derecede artmış olduğu tespit edilmiştir. Alıcı alanda BTx-A ile kas kasılması engellenmeksizin sadece verici alana BTx-A uygulanan grupta hasarlı yağ dokuların daha az olması, BTx-A'nın yağ grefti üzerinde sağ kalım artırıcı etkisinin sadece kas kasılmasını engelleyerek yapmadığını göstermektedir. Alıcı veya verici sahanın botulinum toksin-A ile ön koşullandırılan dokulardaki yağ grefti sağ kalım artışının net mekanizması ve bunun adipoz kökenli kök hücre ile ilişkisi ilerleyen çalışmaların konusu olabilir. Introduction and Purpose: In recent years, autologous fat graft applications have been frequently used in reconstructive and aesthetic surgery. The main advantages of fat graft procedures are; ease of application, harvesting from patients' tissues and the availability of desired amount. The most important disadvantage is the survival rate of fat grafts varies between 20 and 90 percent and this survival rate is unpredictable (Ersek, 1991; Goldwyn, 1988).The botulinium toxin injection is used for wide range of clinical applications such as face lift effect (Kashkouli et al., 2014), scar tissue reduction (Xiao et al., 2011), and increasing the flap survival rate (Chenwang et al., 2009). Studies have shown that, the usage of botulinium toxin A for skin flaps could cause vasodilatation as a result of suppression of sympathetic neurons, thereby increasing the flaps' blood flow and viability. In the literature; this have been related to increased amount of the released mediators, such as VEGF, CD31 (Kim et al., 2009).The purpose of this study is to assess the survival rate of the fat graft after preconditioning the recipient and the donor site which is vascularised and denervated by botulinum toxin-A.Material and Methods: This research was designed as a double blind randomized study. In this study, 40 Wistar rats were randomly divided into 5 groups. In all groups, right inguinal fat pad was used for the fat graft donor area and the interscapular subcutaneous region of the rat was used for the recipient area.In the control group (Group 1); the fat graft was harvested from the right inguinal area as an inguinal fat pad. After suturing the donor site primarily, the fat graft irrigated with saline and adapted into the dorsal subcutaneous region of the rat and the recipient incision was sutured primarily.In the second group; 1.5 U (in 0.75 cc saline) botulinum toxin (BTx-A) was injected on the right inguinal region. Seven days later, the fat graft was harvested from right inguinal area and adapted into the dorsal subcutaneous region with the same procedure. In the third group; 0.75 cc saline was injected on the right inguinal region. Seven days later, the fat graft was harvested from right inguinal area and adapted into the dorsal subcutaneous region with the same procedure.In the fourth group; 1.5 U (in 0.75 cc saline) botulinum toxin (BTx-A) was injected on the dorsal subcutaneous region. Seven days later the fat graft was harvested from right inguinal area and adapted into the dorsal subcutaneous region with the same procedure. In the fifth group; 0.75 cc saline was injected on the dorsal subcutaneous region. Seven days later, the fat graft was harvested from right inguinal area and adapted into the dorsal subcutaneous region with the same procedure.After eight weeks of follow up, fat grafts that were placed in the dorsal region of all rats were examined in terms of weight and volume loss, apoptotic cell entity and then they were evaluated by five histopathological criteria (cyst formation, inflammation, angiogenesis, damaged unilocular fat tissue and new multilocular fat tissue formation).The data of weight and volume differentiation for each group were evaluated by 'Wilcoxon matched pairs signed rank test'. The 'Kruskal-Wallis (non-parametric ANOVA) test' was used to assess histologic parameters to compare the values for five groups. If the values found to be significant in this test, the groups were compared by two groups with 'Dunn multiple comparison test'.Results: In terms of weight and volume reduction in fat grafts, there was no statistically significant difference between the groups (p > 0,05). However, it was observed that the weight loss in the fourth group which BTx- A injection was applied to the dorsal recipient area had the lowest figure whereas the fat graft weight loss in the the control group had the highest figure.There was no significant difference between the groups in terms of apoptotic cell entity, cyst formation, degree of inflammation and angiogenesis (p > 0.05). Although, the angiogenesis was relatively increased in both pre-conditioned donor and recepient areas with BTx-A groups (group 2 and 4).When groups were evaluated in terms of damaged unilocular fat tissue, the ratio of damaged fat tissue was significantly lower (p: 0.0023) in the donor area BTx-A injected group (group 2). In addition to that, the groups were evaluated in terms of new formed multilocular fat tissue and this category was significantly higher (p: 0.0016) in pre-conditioned recipient area with BTx-A group (group 4).Discussion and Conclusion: Fat grafting with botulinum toxin-A is widely used in plastic and reconstructive surgery. However, this combined use is still controversial. In a study conducted by Baek et al., it was demonstrated that cell integrity, fat graft weight and volume increased significantly with the mixture of fat graft and BTx-A. It was concluded that the reason for this significant increase could be related to the inhibition of muscle contractions in the recipient area (Baek et al., 2012). In our study, it was found that the score of damaged fat tissue was significantly lower in pre-conditioned donor area with BTx-A group (without interfering with BTx-A for muscle contraction on the recipient area). This result suggests that the positive effect of the botulinum toxin on fat graft survival is not only caused by inhibition of muscle contraction at recipient area.In an experimental study conducted by Tang et al., it was reported that CD31 and VEGF expression levels increased significantly in the mixture of fat graft and BTx-A group (Tang et al., 2017). However, in our study the survival of the fat graft was examined by preconditioning with BTx-A both on donor and recipient area rather than mixing the fat graft with BTx-A.In conclusion, the fat graft survival rate was investigated after preconditioning the recipient and donor site with BTx-A in our research. We found that the proportion of damaged fat tissue in the fat grafts pre-conditioned with BTx-A at the donor area decreased significantly while the ratio of new fat cells increased significantly in the fat grafts preconditioned with BTx-A at the recipient area. Nevertheless, the net mechanism of fat graft survival in pre-conditioned recipient and donor tissues with botulinum toxin-A and its relation to the adipose-derived stem cells, is still not clear and it could be the subject for further studies. 88

Mesenchymal stem cells (MSCs) are on the cusp of regenerative medicine due to their differentiation capacity, favorable culture conditions, ability to be manipulated in vitro, and strong immunomodulatory activity. Recent studies indicate that the pleiotropic effects of MSCs, especially their immunomodulatory potential, can be largely attributed to paracrine factors. Exosomes, vesicles that are 30-150 nanometers in diameter that function in cell-cell communication, are one of the key paracrine effectors. MSC-derived exosomes are enriched with therapeutic miRNAs, mRNAs, cytokines, lipids, and growth factors. Emerging evidences support the compelling possibility of using MSC-derived exosomes as a new form of therapy for treating several different kinds of disease such as heart, kidney, immune diseases, neural injuries, and neurodegenerative disease. This review provides a summary of current knowledge and discusses engineering of MSC-derived exosomes for their use in translational medicine.

Team-sport athletes and coaches use varied strategies to enhance repeated-sprint ability (RSA). Aside from physical training, a well-conducted warm-up enhances RSA via increased oxidative metabolism. Strategies that impede blood flow could potentiate the effects of a warm-up due to their effects on the endothelial and metabolic functions. This study investigated whether performing a warm-up combined with blood-flow restriction (WFR) induces ergogenic changes in blood volume, muscle oxygenation, and RSA. In a pair-matched, single-blind, pre-post parallel group design, 15 American football players completed an RSA test (12 &times, 20 m, 20 s rest), preceded by WFR or a regular warm-up (SHAM). Pressure was applied on the athletes&rsquo, upper thighs for &asymp, 15 min using elastic bands. Both legs were wrapped at a perceived pressure of 7 and 3 out of 10 in WFR and SHAM, respectively. Changes in gastrocnemius muscle oxygen saturation (SmO2) and total hemoglobin concentration ([THb]) were monitored with near-infrared spectroscopy. Cohen&rsquo, s effect sizes (ES) were used to estimate the impact of WFR. WFR did not clearly alter best sprint time (ES &minus, 0.25), average speed (ES 0.25), total time (ES &minus, 0.12), and percent decrement score (ES 0.39). While WFR did not meaningfully alter average SmO2 and [THb], the intervention clearly increased the maximum [THb] and the minimum and maximum SmO2 during some of the 12 sprint/recovery periods (ES 0.34&ndash, 1.43). Results indicate that WFR positively alters skeletal muscle hemodynamics during an RSA test. These physiological changes did not improve short-term RSA, but could be beneficial to players during longer activities such as games.

Therapeutic angiogenesis promises to aid the healing and regeneration of tissues suffering from a compromised vascular supply. Ischaemia therapy has so far primarily focused on delivering isolated angiogenic growth factors. The limited success of these strategies in clinical trials, however, is increasingly forcing researchers to recognize the difficulties associated with trying to mimic the angiogenic process, due to its natural complexity. Instead, a new school of thought is gradually emerging, focusing on how to induce angiogenesis at its onset, by utilizing hypoxia, the primary angiogenic stimulus in physiological, as well pathological states. This shift in therapeutic approach is underlined by the realization of the importance of depressed HIF-1 α-mediated gene programming in non-healing ischemic tissues, which could explain their apparent habituation to chronic hypoxic stress and the limited capacity to generate adaptive angiogenesis. Hypoxia-based strategies, then effectively aim to override the habituated angiogenic cellular response, re-start the regenerative process and drive it to completion. Here we make a distinction between those strategies that utilize hypoxia in vitro as a preconditioning tool to optimize the angiogenic potential of tissue/cells before transplantation, vs. strategies that aim to induce hypoxia-induced signaling in vivo, directly, through pharmacological means or gene transfer. We then discuss possible future directions for the field, as it moves into the phase of clinical trials.

© 2016, Springer Science+Business Media New York.Ischemic heart disease is a common cause of patients’ death worldwide. Recently, cardiac pre- and post-conditioning (IPC, IPoC) were indentified to reduce infarct size. Nevertheless, not only infarct size but also post-infarct remodelling is critical for the long-term enhancing effect. Calcium-sensing receptors (CaSRs) signalling was shown to be involved in IPC and IPoC in the heart. This study aims to clarify CaSRs expression after ischemia-reperfusion injury (I/R), IPC and IPoC. Experiments were performed on adult Wistar rats with left anterior descending coronary artery (LAD) occlusion. Troponin I (TnI) levels were measured in plasma of all animals to quantify the infarct size. Sham-operated animals, rats with I/R, IPC, and IPoC were compared. Left and right ventricular tissue samples from these groups were collected for qRT-PCR analysis. CaSR expression was enhanced in rats with I/R and IPC. Its increase after IPoC was not pronounced. In contrast, left ventricles (LV) showed decreased CaSR expression in rat hearts after I/R, IPC, and IPoC. Data suggest differences in CaSR regulation between LV and RV. Enhanced CaSR expression in RV was observed in tissue with small infarct size.

Sağlığımızın devamlılığını korumak için önemli bir olgu olan beslenme, aynı zamanda sağlık için tehdit de oluşturabilmektedir. Beslenmedeki bozukluklar sonucu, çeşitli hastalıklara yakalanma riskleri arttığı gibi varolan patofizyolojik süreçler de etkilenebilmektedir. Bu hastalıklardan biri de günümüzde dünya ölüm sıralamalarında ilk üçte yer alan beyin felcidir. Bu çalışmada, kısa dönemli diyet kısıtlamasının fare beyin felci modelindeki, hasar alanı, ödem, nöronal sağkalım ve apoptotik hücre ölümüne olan etkileri incelenmiştir. Bu çalışmada etik kurulu alınmış (karar no:35/2017), 90 ve 30 dakikalık (sırasıyla 24 ve 72 saat reperfüzyon) orta serebral arter tıkanması modeli uygulanan 8-12 haftalık erkek BALB/c fareler kullanılmıştır. Fareler operasyondan üç gün önce gruplarına göre hazırlanmış %70 yoğunluktaki (n=7; protein, yağ, karbonhidrat) diyetlerle beslenmişlerdir. Kontrol grubu standart yemle beslenmeye devam ederken, açlık grubunun yemleri çekilerek sadece suya erişimine izin verilmiştir. İstatistik olarak one-way ANOVA yöntemi kullanılmıştır. Yüksek yağlı diyetle beslenen hayvanlarda, 90 ve 30 dakika iskemideki Laser Doppler flowmetri kayıtlarında, kontrol ve diğer gruplara göre hipoperfüzyon gözlenmiştir. Buna ilaveten 90 dakika iskemide yüksek yağlı diyetle beslenen hayvanlarda kontrol grubuna kıyasla beyindeki hasarın ve ödemin anlamlı olarak artmış olduğu görüldü. Hücresel sağkalıma bakıldığında, yüksek yağ ve yüksek karbonhidrat gruplarında kontrol grubuna kıyasla canlı hücre sayısında anlamlı bir azalma izlenmiştir. Bu çalışmada diyet restriksiyonunun fare beyin felci modelindeki etkisi araştırılmıştır. Elde edilen sonuçlar doğrultusunda beslenmenin beyin felci süreçlerini etkilediğini göstermektedir. Nutrition is an important factor in order to maintain our healthy state. However, it can also become a major threat in the cases of malnutrition. Malnutrition affects several pathophysiological processes and also increases susceptibility to a number of diseases. Cerebral ischemia is an example for such diseases and is the third main reason of mortality worldwide. In this study, we examined the effects of short-term diet restriction using a cerebral ischemia model in mice in terms of infarct volume, edema formation, neuronal survival and apoptotic cell death. This study was carried out in 8-12 weeks old BALB/c mice; with the permission from the Medipol University Ethical board (#35/2017). 90 and 30 minutes (followed by 24 and 72 hours of reperfusion, respectively) of middle cerebral artery occlusion were performed. Animals were fed with %70 high density diets (n=7, protein, fat or carbohydrate) three days prior to middle cerebral artery occlusion. The fasting group was given ad libitum access to water only, whereas the control group was fed on standard mice food. The animals that had high-fat diets showed hypoperfusion on the Laser Doppler flowmeter records on both 90 and 30 minutes of middle cerebral artery occlusion when compared with control and the other diet groups. Also, within the same group, the mice that had gone under 90 minutes of occlusion period had increased edema and infarct volume compared with the control group. Furthermore, the decrease in the neuronal survival rates of the high fat and high carbohydrate groups was statistically significant when compared with the control group. This study focuses on the effects of diet restriction on the recovery processes including neuronal survival and apoptotic cell death following cerebral ischemic injury in mice. Our results suggest that nutrition results in differential effects on the recovery processes, and therefore further studies should be conducted to identify the underlying mechanisms of the beneficial effects of dieting. 65

Amaç: Bu çalışmada alt ekstremitede oluşturulan iskemi-reperfüzyon ile oluşturulan erken ve geç iskemik önkoşullanma modelinde, antioksidan ve antiinflamatuar özelliği olan polidatin kullanımının karaciğer preservasyonuna katkısının olup olmayacağını, olursa nasıl bir etki sağlayacağının araştırılması planlandı. Yöntem: Bu amaçla Wistar Albino türü ratlar rastgele beş gruba ayrıldı. Üç gün intraperitoneal polidatin verilen iki grup ile polidatin verilmeyen diğer iki gruptaki deney hayvanlarında, alt ekstremite proksimalinde yapılan iskemi ve reperfüzyon sonrası erken ve geç iskemik önkoşullanma oluşturularak karaciğer dokusunda serbest oksijen radikalleri ve inflamatuar lenfosittik sitokinlerin hasar değerlendirmesi yapıldı. Birinci grup kontrol grubu olarak seçildi, intraperitoneal serum fizyolojik enjeksiyonu dışında herhangi bir uygulama yapılmadı. Deney sonunda kan ve doku örnekleri alındıktan sonra hayvanlar dekapite edildi.Bulgular: Karaciğer fonksiyonlarını değerlendirmek amacıyla aspartataminotransaminaz (AST), alaninaminotransaminaz (ALT), laktat dehidrogenaz (LDH), albümin, total protein seviyeleri ölçüldü. Oksidatif stresi belirlemek için TAS, TOS ve HIF 1 alfa plazmada ölçüldü. Karaciğer doku örneklerinde katalaz, süperoksit dismutaz (SOD) ve GSH-Px ölçüldü. Alınan karaciğer doku örnekleri Hemotoksilen Eosin ile boyandıktan sonra histopatolojik olarak ışık mikroskopunda incelendi.Sonuç: Bu çalışmanın sonucuna dayanarak, Polidatin'in antioksidatif ve antienflamatuar özelliğinden dolayı iskemik önkoşullanma modelinde karaciğer preservasyonuna pozitif etki sağladığı düşünüldü.Anahtar kelimeler: Karaciğer, iskemik önkoşullanma, polidatin, antioksidan. Aim: In this study, it was planned to investigate whether or not there will be an additional contribution to liver preservation as a result of combined use of antioxidant and antiinflammatory polydatin in the early and late ischemic preconditioning model created by ischemia-reperfusion in the lower extremity.Methods: For this purpose, Wistar Albino type rats were randomly divided into five groups. Two groups receiving intraperitoneal polydatin for three days and the other two groups without polydatin were evaluated for damage to free oxygen radicals and inflammatory cytokines in liver tissue as distant organ in the early and late ischemic preconditioning model after ischemia and reperfusion in the proximal lower extremity. The first group was selected as the control group and no application except intraperitoneal saline injection was made. At the end of the experiment, the animals were decapitated and blood and tissue samples were taken.Results: Aspartataminotransaminase (AST), alaninaminotransaminase (ALT), lactate dehydrogenase (LDH), albumin, total protein levels were measured to evaluate liver functions. TAS, TOS and HIF 1 alpha were measured in plasma to determine oxidative stress. Catalase, superoxide dismutase (SOD) and GSH-Px were measured in liver tissue samples. Liver tissue specimens were stained with hematoxylin eosin and then histopathologically examined under light microscope.Conclusion: Based on the results of this study, it is thought that Polydatin has positive effect on liver preservation as a remote organ in the ischemic preconditioning model due to antioxidative and antiinflammatory properties of polydatin.Keyworlds: Liver, ischemic preconditioning, polydatin, antioxidants 65

Rubber-like materials as many soft tissues can be described as incompressible and hyper-elastic materials. Their comparable elastic behavior, up to a certain extent, has been exploited to develop and test experimental methodologies to be then applied to soft biological tissues such as aortic wall. Hence, theoretical and experimental simulation of aortic tissue, and more generally blood vessel tissue, has been often conducted using rubbers. Despite all the efforts in characterizing such materials, a clear and comprehensive testing procedure is still missing. In particular, the influence of pre-conditioning in the mechanical response of hyper-elastic materials has been often neglected. In this paper, the importance of pre-conditioning is demonstrated by: (i) exploring the effect of stretching frequency applied before the uniaxial tensile test; (ii) recognizing the role of specimen geometry and strain amplitude; (iii) verifying the impact of experimental data acquisition on finite element predictions. It was found that stress–strain relationship shows a statistical difference between some frequencies of pre-conditioning and its absence. Only certain pre-conditioning frequencies were able to generate repeatable experimental data for strip or dumb-bell shapes. This feature corresponds to a consistent reduction in the scatter of critical pressures obtained by numerical simulations.