Processing, characterisation and oxidation resistance of βNiAl bond coat: Al and Zr effects

Platinum-modified-?NiAl is a bond coat (BC) material for thermal barrier coatings (TBCs) applications applied on aero-engine hardware to reduce their surface temperatures. However, it is desirable to minimize its production and material costs by the low-cost alternatives of similar performance. As, it has been acknowledged that the small concentration of the reactive elements (REs), such as Zr, Hf, and Y, could tremendously enhance the oxide adhesion even in some cases better than Pt modified counterparts. The present study aims to design and fabricate the Zr-modified-?NiAl bond coat on CMSX-4 superalloy using an aluminizing method. Moreover, the study focuses on the development of a systematic understanding of underlying mechanisms behind the beneficial effects of REs. Initially, three sets of BCs were prepared: Zr-free ?NiAl (undoped), Al and Zr co-deposited in a single-step process (1SP), and Zr and Al, which were individually deposited in two processing steps (2SP): zirconizing and aluminizing. Such three sets of BCs help to understand the processing, as well as Zr and Al effects on scale adhesion. In particular, 1SP/2SP BCs showed uniformity of Zr in the form of precipitates and networks that caused hardness enhancement. All BCs were isothermally oxidized at 1150oC for 100 hours wherein 2SP revealed the best spallation resistance, microstructural stability and its Zr-oxide pegs were extended to substrates. In addition to the Zr effect, BC Al content was found to affect the oxide adhesion equally. Under identical Zr contents (of 1SP and 2SP = 1at %), the higher Al showed the better spallation resistance while lower Al caused the inverse effect of Zr owing to its reactive nature that is termed as over doping. Moreover, it has been established that over-doping either local or into entire BC, accelerates the Al depletion that destabilizes the ?NiAl into ??-Ni3Al phase. An extensive discussion is presented in the light of observed results.

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Dehulled Adlay Consumption Modulates Blood Pressure in Spontaneously Hypertensive Rats and Overweight and Obese Young Adults

Nutrients ◽

10.3390/nu13072305 ◽

2021 ◽

Vol 13 (7) ◽

pp. 2305

Author(s):

Wan-Ju Yeh ◽

Jung Ko ◽

Wei-Yi Cheng ◽

Hsin-Yi Yang

Keyword(s):

Blood Pressure ◽

Daily Intake ◽

Experimental Period ◽

Overweight And Obesity ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Beneficial Effects ◽

Underlying Mechanisms ◽

Grain Foods

High blood pressure is a crucial risk factor for many cardiovascular diseases, and a diet rich in whole-grain foods may modulate blood pressure. This study investigated the effects of dehulled adlay consumption on blood pressure in vivo. We initially fed spontaneous hypertensive rats diets without (SHR group) or with 12 or 24% dehulled adlay (SHR + LA and SHR + HA groups), and discovered that it could limit blood pressure increases over a 12-week experimental period. Although we found no significant changes in plasma, heart, and kidney angiotensin-converting enzyme activities, both adlay-consuming groups had lower endothelin-1 and creatinine concentrations than the SHR group; the SHR + HA group also had lower aspartate aminotransferase and uric acid levels than the SHR group did. We later recruited 23 participants with overweight and obesity, and they consumed 60 g of dehulled adlay daily for a six-week experimental period. At the end of the study, we observed a significant decrease in the group’s systolic blood pressure (SBP), and the change in SBP was even more evident in participants with high baseline SBP. In conclusion, our results suggested that daily intake of dehulled adlay had beneficial effects in blood-pressure management. Future studies may further clarify the possible underlying mechanisms for the consuming of dehulled adlay as a beneficial dietary approach for people at risk of hypertension.

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Beneficial effects of natural compounds on experimental liver ischemia-reperfusion injury

Food & Function ◽

10.1039/d1fo00289a ◽

2021 ◽

Author(s):

Camila Dossi ◽

Romina Vargas ◽

Rodrigo Valenzuela ◽

Luis Videla

Keyword(s):

Reperfusion Injury ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Natural Compounds ◽

Liver Ischemia ◽

Hepatic Surgery ◽

Beneficial Effects ◽

Underlying Mechanisms ◽

Experimental Liver

Liver ischemia-reperfusion injury (IRI) is a phenomenon inherent to hepatic surgery that severely compromises the organ functionality, whose underlying mechanisms involve cellular and molecular interrelated processes leading to the development...

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Intranasal insulin rescues repeated anesthesia-induced deficits in synaptic plasticity and memory and prevents apoptosis in neonatal mice via mTORC1

Scientific Reports ◽

10.1038/s41598-021-94849-3 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Patricia Soriano Roque ◽

Mehdi Hooshmandi ◽

Laura Neagu-Lund ◽

Shelly Yin ◽

Noosha Yousefpour ◽

...

Keyword(s):

Cognitive Impairment ◽

Synaptic Plasticity ◽

General Anesthesia ◽

Preventive Treatment ◽

Intranasal Insulin ◽

Translational Repressor ◽

Beneficial Effects ◽

Underlying Mechanisms ◽

Induced Apoptosis ◽

Preclinical And Clinical Studies

AbstractLong-lasting cognitive impairment in juveniles undergoing repeated general anesthesia has been observed in numerous preclinical and clinical studies, yet, the underlying mechanisms remain unknown and no preventive treatment is available. We found that daily intranasal insulin administration to juvenile mice for 7 days prior to repeated isoflurane anesthesia rescues deficits in hippocampus-dependent memory and synaptic plasticity in adulthood. Moreover, intranasal insulin prevented anesthesia-induced apoptosis of hippocampal cells, which is thought to underlie cognitive impairment. Inhibition of the mechanistic target of rapamycin complex 1 (mTORC1), a major intracellular effector of insulin receptor, blocked the beneficial effects of intranasal insulin on anesthesia-induced apoptosis. Consistent with this finding, mice lacking mTORC1 downstream translational repressor 4E-BP2 showed no induction of repeated anesthesia-induced apoptosis. Our study demonstrates that intranasal insulin prevents general anesthesia-induced apoptosis of hippocampal cells, and deficits in synaptic plasticity and memory, and suggests that the rescue effect is mediated via mTORC1/4E-BP2 signaling.

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In vitro evidence for the involvement of H2S pathway in the effect of clodronate during inflammatory response

Scientific Reports ◽

10.1038/s41598-021-94228-y ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Rosangela Montanaro ◽

Alessio D’Addona ◽

Andrea Izzo ◽

Carlo Ruosi ◽

Vincenzo Brancaleone

Keyword(s):

Inflammatory Markers ◽

In Vitro Study ◽

Inos Expression ◽

Beneficial Effects ◽

Tnf Α ◽

Inflammatory State ◽

Anti Inflammatory ◽

Underlying Mechanisms ◽

Inflammatory Effect

AbstractClodronate is a bisphosphonate agent commonly used as anti-osteoporotic drug. Throughout its use, additional anti-inflammatory and analgesic properties have been reported, although the benefits described in the literature could not solely relate to their inhibition of bone resorption. Thus, the purpose of our in vitro study is to investigate whether there are underlying mechanisms explaining the anti-inflammatory effect of clodronate and possibly involving hydrogen sulphide (H2S). Immortalised fibroblast-like synoviocyte cells (K4IM) were cultured and treated with clodronate in presence of TNF-α. Clodronate significantly modulated iNOS expression elicited by TNF-α. Inflammatory markers induced by TNF-α, including IL-1, IL-6, MCP-1 and RANTES, were also suppressed following administration of clodronate. Furthermore, the reduction in enzymatic biosynthesis of CSE-derived H2S, together with the reduction in CSE expression associated with TNF-α treatment, was reverted by clodronate, thus rescuing endogenous H2S pathway activity. Clodronate displays antinflammatory properties through the modulation of H2S pathway and cytokines levels, thus assuring the control of the inflammatory state. Although further investigation is needed to stress out how clodronate exerts its control on H2S pathway, here we showed for the first the involvement of H2S in the additive beneficial effects observed following clodronate therapy.

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Repurposing of Antimicrobial Agents for Cancer Therapy: What Do We Know?

Cancers ◽

10.3390/cancers13133193 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3193

Author(s):

Christina Pfab ◽

Luisa Schnobrich ◽

Samir Eldnasoury ◽

André Gessner ◽

Nahed El-Najjar

Keyword(s):

Clinical Trials ◽

Antimicrobial Agents ◽

Large Body ◽

Drug Repurposing ◽

Extensive Discussion ◽

Attrition Rates ◽

Beneficial Effects ◽

Stage Of Development ◽

Development Costs ◽

Approved Drugs

The substantial costs of clinical trials, the lengthy timelines of new drug discovery and development, along the high attrition rates underscore the need for alternative strategies for finding quickly suitable therapeutics agents. Given that most approved drugs possess more than one target tightly linked to other diseases, it encourages promptly testing these drugs in patients. Over the past decades, this has led to considerable attention for drug repurposing, which relies on identifying new uses for approved or investigational drugs outside the scope of the original medical indication. The known safety of approved drugs minimizes the possibility of failure for adverse toxicology, making them attractive de-risked compounds for new applications with potentially lower overall development costs and shorter development timelines. This latter case is an exciting opportunity, specifically in oncology, due to increased resistance towards the current therapies. Indeed, a large body of evidence shows that a wealth of non-cancer drugs has beneficial effects against cancer. Interestingly, 335 drugs are currently being evaluated in different clinical trials for their potential activities against various cancers (Redo database). This review aims to provide an extensive discussion about the anti-cancer activities exerted by antimicrobial agents and presents information about their mechanism(s) of action and stage of development/evaluation.

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Effects of Aluminum Doping on The Phase Stability and Electrochemical Properties of LiCoO2 and LiMnO2

MRS Proceedings ◽

10.1557/proc-496-403 ◽

1997 ◽

Vol 496 ◽

Cited By ~ 3

Author(s):

Y.-I. Jang ◽

B. Huang ◽

H. Wang ◽

Y.-M. Chiang ◽

D. R. Sadoway

Keyword(s):

Single Phase ◽

Low Cost ◽

Reversible Capacity ◽

Open Circuit ◽

Teller Distortion ◽

Al Content ◽

Jahn Teller ◽

Li Battery ◽

Low Mass ◽

Jahn Teller Distortion

ABSTRACTAluminum is of interest as a constituent for Li battery electrodes due to its low cost and low mass, and because ab initio calculations indicate that solid solution of LiAlO2 with LiMO2 (M = transition metal) in the α-NaFeO2 structure can increase intercalation voltage [1]. In this study, we investigated the effect of Al doping on LiCoO2 and LiMnO2. Single phase LiAlyCo1-yO2 has been synthesized up to y = 0.5 by firing homogenous hydroxide precursors. A systematic increase in the open circuit voltage is observed with Al content. In LiAlyMn1-yO2, the addition of LiAlO2 stabilizes LiMnO2 in the α-NaFeO2 structure under conditions where neither endmember is stable in the structure. High reversible capacity was obtained over both a 4 V and 3 V plateau, indicating that the compound transforms to a spinel-related structure during cycling, but that the cooperative Jahn-Teller distortion is suppressed.

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Dexmedetomidine Attenuates Blood-Spinal Cord Barrier Disruption Induced by Spinal Cord Ischemia Reperfusion Injury in Rats

Cellular Physiology and Biochemistry ◽

10.1159/000430107 ◽

2015 ◽

Vol 36 (1) ◽

pp. 373-383 ◽

Cited By ~ 25

Author(s):

Bo Fang ◽

Xiao-Qian Li ◽

Bo Bi ◽

Wen-Fei Tan ◽

Gang Liu ◽

...

Keyword(s):

Spinal Cord ◽

Motor Neurons ◽

Ischemia Reperfusion Injury ◽

Ischemia Reperfusion ◽

Spinal Cord Ischemia ◽

Beneficial Effects ◽

Polymerase Chain ◽

Underlying Mechanisms ◽

Blood Spinal Cord Barrier ◽

Metalloproteinase 9

Background/Aims: Dexmedetomidine has beneficial effects on ischemia reperfusion (I/R) injury to the spinal cord, but the underlying mechanisms are not fully understood. This study investigated the effects and possible mechanisms of dexmedetomidine on blood-spinal cord barrier (BSCB) disruption induced by spinal cord I/R injury. Methods: Rats were intrathecally pretreated with dexmedetomidine or PBS control 30 minutes before undergoing 14-minute occlusion of aortic arch. Hind-limb motor function was assessed using Tarlov criteria, and motor neurons in the ventral gray matter were counted by histological examination. The permeability of the BSCB was examined using Evans blue (EB) as a vascular tracer. The spinal cord edema was evaluated using the wet-dry method. The expression and localization of matrix metalloproteinase-9 (MMP-9), Angiopoietin-1 (Ang1) and Tie2 were assessed by western blot, real-time polymerase chain reaction, and immunofluorescence. Results: Intrathecal preconditioning with dexmedetomidine minimized the neuromotor dysfunction and histopathological deficits, and attenuated EB extravasation after spinal cord I/R injury. In addition, dexmedetomidine preconditioning suppressed I/R-induced increase in MMP-9. Finally, Dexmedetomidine preconditioning enhanced the Ang1-Tie2 system activity after spinal cord I/R injury. Conclusions: Dexmedetomidine preconditioning stabilized the BSCB integrity against spinal cord I/R injury by inhibition of MMP-9, and enhancing the Ang1-Tie2 system.

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Targeting necroptosis as therapeutic potential in chronic myocardial infarction

Journal of Biomedical Science ◽

10.1186/s12929-021-00722-w ◽

2021 ◽

Vol 28 (1) ◽

Author(s):

Chanon Piamsiri ◽

Chayodom Maneechote ◽

Natthaphat Siri-Angkul ◽

Siriporn C. Chattipakorn ◽

Nipon Chattipakorn

Keyword(s):

Myocardial Infarction ◽

Therapeutic Potential ◽

Coronary Perfusion ◽

Beneficial Effects ◽

Cell Death Pathways ◽

Threatening Condition ◽

Underlying Mechanisms ◽

Novel Therapeutic Strategies

AbstractCardiovascular diseases (CVDs) are considered the predominant cause of morbidity and mortality globally. Of these, myocardial infarction (MI) is the most common cause of CVD mortality. MI is a life-threatening condition which occurs when coronary perfusion is interrupted leading to cardiomyocyte death. Subsequent to MI, consequences include adverse cardiac remodeling and cardiac dysfunction mainly contribute to the development of heart failure (HF). It has been shown that loss of functional cardiomyocytes in MI-induced HF are associated with several cell death pathways, in particular necroptosis. Although the entire mechanism underlying necroptosis in MI progression is still not widely recognized, some recent studies have reported beneficial effects of necroptosis inhibitors on cell viability and cardiac function in chronic MI models. Therefore, extensive investigation into the necroptosis signaling pathway is indicated for further study. This article comprehensively reviews the context of the underlying mechanisms of necroptosis in chronic MI-induced HF in in vitro, in vivo and clinical studies. These findings could inform ways of developing novel therapeutic strategies to improve the clinical outcomes in MI patients from this point forward.

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Abstract 123: SUMO1 Modification Regulates SR Calcium ATPase Pump, SERCA2a in Heart Failure

Circulation Research ◽

10.1161/res.111.suppl_1.a123 ◽

2012 ◽

Vol 111 (suppl_1) ◽

Author(s):

Changwon Kho ◽

Ahyoung Lee ◽

Dongtak Jeong ◽

Jae Gyun Oh ◽

Antoine Chaanine ◽

...

Keyword(s):

Heart Failure ◽

Cardiac Function ◽

Calcium Atpase ◽

Post Translational Modifications ◽

Beneficial Effects ◽

Protein Levels ◽

In Trans ◽

Underlying Mechanisms ◽

Hemodynamic Performance ◽

Reduced Activity

Background: The cardiac calcium ATPase, SERCA2a, is a critical pump responsible for Ca2+ re-uptake during excitation-contraction coupling. Impaired Ca2+ uptake resulting from decreased expression and reduced activity of SERCA2a is a hallmark of heart failure. Accordingly, restoration of SERCA2a expression by gene transfer has proved to be effective in improving cardiac function in heart-failure patients, as well as in animal models. However, the underlying mechanisms of SERCA2a’s dysfunction remain incompletely understood. Methods and Results: In this study, we show that SERCA2a is modified by SUMO1 at lysine sites 480 and 585 and that this SUMOylation is essential for preserving SERCA2a ATPase activity and stability in mouse and human cells. SUMO1 and SERCA2a SUMOylation levels were both decreased in mouse and pig models of heart failure and failing human left ventricles. To determine whether reduced SUMO1 levels are responsible for reduced SERCA2a protein levels and reduced cardiac function, we used an adenovirus associated virus-mediated gene delivery approach to up-regulate SUMO1 in trans aortic constriction-induced mouse model of heart failure. We found that increasing SUMO1 levels led to a restoration of SERCA2a levels, improved hemodynamic performance, and reduced mouse mortality. By contrast, down-regulation of SUMO1 using small hairpin RNA accelerated cardiac functional deterioration and was accompanied by decreased SERCA2a function. Conclusion: In this study, we study a new mechanism for modulation of SERCA2a activity and beneficial effects of SUMO1 in the setting of heart failure. It suggests that changes in post-translational modifications of SERCA2a could negatively affect cardiac function in heart failure. Our data may provide a new platform for the design of therapeutic strategies for heart failure.

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Exercise training normalizes elevated firing rate of hypothalamic presympathetic neurons in heart failure rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00225.2018 ◽

2019 ◽

Vol 316 (2) ◽

pp. R110-R120 ◽

Cited By ~ 2

Author(s):

Yiming Shen ◽

Jin Bong Park ◽

So Yeong Lee ◽

Seong Kyu Han ◽

Pan Dong Ryu

Keyword(s):

Heart Failure ◽

Exercise Training ◽

Firing Rate ◽

Gaba Release ◽

Neuronal Firing ◽

Ventrolateral Medulla ◽

Patch Clamp Technique ◽

Electrophysiological Properties ◽

Beneficial Effects ◽

Underlying Mechanisms

Exercise training (ExT) normalizes elevated sympathetic nerve activity in heart failure (HF), but the underlying mechanisms are not well understood. In this study, we examined the effects of 3 wk of ExT on the electrical activity of the hypothalamic presympathetic neurons in the brain slice of HF rats. HF rats were prepared by ligating the left descending coronary artery. The electrophysiological properties of paraventricular nucleus neurons projecting to the rostral ventrolateral medulla (PVN-RVLM) were examined using the slice patch-clamp technique. The neuronal firing rate was elevated in HF rats, and ExT induced a reduction in the firing rate ( P < 0.01). This ExT-induced decrease in the firing rate was associated with an increased frequency of spontaneous and miniature inhibitory postsynaptic current (IPSCs; P < 0.05). There was no significant change in excitatory postsynaptic current. Replacing Ca2+ with Mg2+ in the recording solution reduced the elevated IPSC frequency in HF rats with ExT ( P < 0.01) but not in those without ExT, indicating an increase in the probability of GABA release. In contrast, ExT did not restore the reduced GABAA receptor-mediated tonic inhibitory current in HF rats. A GABAA receptor blocker (bicuculline, 20 μM) increased the firing rate in HF rats with ExT ( P < 0.01) but not in those without ExT. Collectively, these results show that ExT normalized the elevated firing activity by increasing synaptic GABA release in PVN-RVLM neurons in HF rats. Our findings provide a brain mechanism underlying the beneficial effects of ExT in HF, which may shed light on the pathophysiology of other diseases accompanied by sympathetic hyperactivation.

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