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https://www.readbyqxmd.com/read/28803066/a-novel-ripk1-inhibitor-that-prevents-retinal-degeneration-in-a-rat-glaucoma-model
#1
Yun-Ju Do, Jee-Won Sul, Ki-Hong Jang, Nam Sook Kang, Young-Hoon Kim, Young-Gwan Kim, Eunhee Kim
In glaucoma, retinal ganglion cells (RGCs) are exposed to ischemic stress with elevation of the intraocular pressure and are subsequently lost. Necroptosis, a type of regulated necrosis, is known to play a pivotal role in this loss. We observed that receptor-interacting protein kinase 1 (RIPK1), the key player of necroptosis, was activated by diverse ischemic stresses, including TCZ, chemical hypoxia (CH), and oxygen glucose deprivation (OGD). In this study, we introduce a RIPK1-inhibitory compound (RIC) with a novel scaffold...
August 9, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28765969/ampk-activation-restores-ischemic-post%C3%A2-conditioning-cardioprotection-in-stz%C3%A2-induced-type-1-diabetic-rats-role-of-autophagy
#2
Bin Zhou, Yan Leng, Shao-Qing Lei, Zhong-Yuan Xia
Although the mechanism remains unclear, ischemic post‑conditioning (IPO) is a promising approach to combat myocardial ischemia reperfusion (IR) injury; however, it has been proven ineffective in diabetes. The present study aimed to identify whether hyperglycemia‑induced AMP‑activated protein kinase (AMPK) inhibition contributes to the ineffectiveness of IPO via autophagy attenuation in diabetic hearts. Diabetic and non‑diabetic rats were subjected to myocardial IR and/or IPO with/without treatment with the AMPK activator A‑769662 and/or autophagy inhibitor 3‑methyladenine (3‑MA)...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28762914/-adaptation-to-intermittent-hypoxia-hyperoxia-in-the-rehabilitation-of-patients-with-ischemic-heart-disease-exercise-tolerance-and-quality-of-life
#3
A L Syrkin, O S Glazachev, F Y Kopylov, E N Dudnik, E E Zagaynaya, D S Tuter
AIM: to assess effect of interval hypoxic-hyperoxic training (IT) on exercise tolerance and quality of life of patients with ischemic heart disease (IHD) receiving optimal medical therapy, as well as the safety of IHHT use. METHODS: Patients with stable IHD with functional class II and III angina (n=46) were randomized into two groups: IHHT (n=27, 15 treatments in 3 weeks), and IHHT imitation (n=19). Cardiopulmonary stress test was performed to evaluate the following parameters of exercise tolerance: peak oxygen consumption (VO2peak, VO2peak/kg), % of predicted peak oxygen consumption (%VO2 peak) and anaerobic threshold (VO2AT)...
May 2017: Kardiologiia
https://www.readbyqxmd.com/read/28735240/therapeutic-effects-of-l-cysteine-in-newborn-mice-subjected-to-hypoxia-ischemia-brain-injury-via-the-cbs-h2s-system-role-of-oxidative-stress-and-endoplasmic-reticulum-stress
#4
Song Liu, Danqing Xin, Lingxiao Wang, Tiantian Zhang, Xuemei Bai, Tong Li, Yunkai Xie, Hao Xue, Shishi Bo, Dexiang Liu, Zhen Wang
Neonatal hypoxic-ischemic (HI) injury is a major cause of neonatal death and neurological dysfunction. H2S has been shown to protect against hypoxia-induced injury and apoptosis of neurons. L-Cysteine is catalyzed by cystathionine-β-synthase (CBS) in the brain and sequentially produces endogenous H2S. The present study was designed to investigate whether L-Cysteine could attenuate the acute brain injury and improve neurobehavioral outcomes following HI brain injury in neonatal mice by releasing endogenous H2S...
July 14, 2017: Redox Biology
https://www.readbyqxmd.com/read/28714516/-epigallocatechin-3-gallate-attenuates-myocardial-injury-induced-by-ischemia-reperfusion-in-diabetic-rats-and-in-h9c2-cells-under-hyperglycemic-conditions
#5
Yang Wu, Zhong-Yuan Xia, Bo Zhao, Yan Leng, Juan Dou, Qing-Tao Meng, Shao-Qing Lei, Zhi-Ze Chen, Jie Zhu
(-)-Epigallocatechin gallate (EGCG) exerts multiple beneficial effects on cardiovascular performance. In this study, we aimed to examine the effects of EGCG on diabetic cardiomyopathy during myocardial ischemia/reperfusion (I/R) injury. EGCG (100 mg/kg/day) was administered at week 6 for 2 weeks to diabetic rats following the induction of type 1 diabetes by streptozotocin (STZ). At the end of week 8, the animals were subjected to myocardial I/R injury. The EGCG-elicited structural and functional effects were analyzed...
August 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28698612/eif2%C3%AE-signaling-regulates-ischemic-osteonecrosis-through-endoplasmic-reticulum-stress
#6
Daquan Liu, Yunlong Zhang, Xinle Li, Jie Li, Shuang Yang, Xiaoxue Xing, Guanwei Fan, Hiroki Yokota, Ping Zhang
Osteonecrosis of the femoral head (ONFH) primarily results from ischemia/hypoxia to the femoral head, and one of the cellular manifestations is the endoplasmic reticulum (ER) stress. To understand possible linkage of ischemic osteonecrosis to the ER stress, a surgery-induced animal model was employed and salubrinal was administered to evaluate the role of ER stress. Salubrinal is a synthetic chemical that inhibits de-phosphorylation of eIF2α, and it can suppress cell death from the ER stress at a proper dose...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28698499/molecular-mechanisms-behind-free-radical-scavengers-function-against-oxidative-stress
#7
REVIEW
Fereshteh Ahmadinejad, Simon Geir Møller, Morteza Hashemzadeh-Chaleshtori, Gholamreza Bidkhori, Mohammad-Saeid Jami
Accumulating evidence shows that oxidative stress is involved in a wide variety of human diseases: rheumatoid arthritis, Alzheimer's disease, Parkinson's disease, cancers, etc. Here, we discuss the significance of oxidative conditions in different disease, with the focus on neurodegenerative disease including Parkinson's disease, which is mainly caused by oxidative stress. Reactive oxygen and nitrogen species (ROS and RNS, respectively), collectively known as RONS, are produced by cellular enzymes such as myeloperoxidase, NADPH-oxidase (nicotinamide adenine dinucleotide phosphate-oxidase) and nitric oxide synthase (NOS)...
July 10, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28657795/p38-mapk-inhibition-improves-heart-function-in-pressure-loaded-right-ventricular-hypertrophy
#8
Baktybek Kojonazarov, Tatyana Novoyatleva, Mario Boehm, Chris Happe, Zaneta Sibinska, Xia Tian, Amna Sajjad, Himal Luitel, Guido Posern, Steven M Evans, Friedrich Grimminger, Hossein A Ghofrani, Norbert Weissmann, Harm J Bogaard, Werner Seeger, Ralph T Schermuly
While p38 MAPK is known to have a role in ischemic heart disease and many other diseases, its contribution to the pathobiology of right ventricular (RV) hypertrophy and failure is unclear. Therefore, we sought to investigate the role of p38 MAPK to the pathophysiology of pressure overload-induced RV hypertrophy and failure. Measurements and Main Results The effects of the p38 MAPK inhibitor PH797804 were investigated in mice with RV hypertrophy/failure caused by exposure to hypoxia or pulmonary artery banding (PAB); in addition, the effects of p38 MAPK inhibition or depletion (by small interfering RNA) were studied in isolated mouse RV fibroblasts...
June 28, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28656194/excessive-nnos-no-ampk-signaling-activation-mediated-by-the-blockage-of-the-cbs-h2s-system-contributes-to-oxygen%C3%A2-glucose-deprivation%C3%A2-induced-endoplasmic-reticulum-stress-in-pc12%C3%A2-cells
#9
Rui Zhang, Yong-Quan Lin, Wei-Sheng Wang, Xin-Qiang Wang
Hypoxic‑ischemia stress causes severe brain injury, leading to death and disability worldwide. Although it has been reported that endoplasmic reticulum (ER) stress is an essential step in the progression of hypoxia or ischemia‑induced brain injury, the underlying molecular mechanisms are and have not yet been fully elucidated. Accumulating evidence has indicated that both nitric oxide (NO) and hydrogen sulfide (H2S) play an important role in the development of cerebral ischemic injury. In the present study, we aimed to investigate the effect of the association between NO signaling and the cystathionine β‑synthase (CBS)/H2S system on ER stress in a cell model of cerebral hypoxia‑ischemia injury...
June 21, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28634450/leonurine-improves-age-dependent-impaired-angiogenesis-possible-involvement-of-mitochondrial-function-and-hif-1%C3%AE-dependent-vegf-activation
#10
Jia Qi, Jing J Wang, Jun L Duan, Zhao Y Lu, Yang G Yuan
Objective: Advanced age is associated with impaired angiogenesis in part because of mitochondrial dysfunction. We have recently reported that leonurine exerts protective effects in neuron via regulation of mitochondrial function. The aim of this study was to explore whether leonurine is able to attenuate mitochondrial dysfunction and to enhance angiogenesis in old rats with hindlimb ischemia. Methods and Results: At day 14 after surgery, hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) expression was decreased in the ischemic muscle of aged animals, which was accompanied by enhanced oxidative stress, increased mitochondrial damage, decreased capillary density, and reduced limb perfusion compared with young mice...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28629519/erythropoietin-endogenous-protection-of-ischemic-brain
#11
Robert T Mallet, Myoung-Gwi Ryou
The human brain requires uninterrupted delivery of blood-borne oxygen and nutrients to sustain its function. Focal ischemia, particularly, ischemic stroke, and global ischemia imposed by cardiac arrest disrupt the brain's fuel supply. The resultant ATP depletion initiates a complex injury cascade encompassing intracellular Ca(2+) overload, glutamate excitotoxicity, oxido-nitrosative stress, extracellular matrix degradation, and inflammation, culminating in neuronal and astroglial necrosis and apoptosis, neurocognitive deficits, and even death...
2017: Vitamins and Hormones
https://www.readbyqxmd.com/read/28625734/synthesis-and-cardiomyocyte-protection-activity-of-crocetin-diamide-derivatives
#12
Jin Gao, Ming Chen, Xue-Cong Ren, Xiao-Bo Zhou, Qiang Shang, Wen-Qi Lu, Pei Luo, Zhi-Hong Jiang
A series of novel diamide derivatives (2-8) of crocetin (1) were synthesized and evaluated for their cardioprotective activity in vitro. Using well-established model of hypoxia-induced injury in H9c2 cells, we investigated the effects of 9 compounds and positive drug nicorandil on cellular cytotoxicity by MTT assay, mitochondrial viable staining, LDH activity and mitochondrial membrane potential (MMP). Among the new derivatives, compounds 3 and 4 with good liposolubility showed significantly potent activity than crocetin (1) against hypoxia-induced cytotoxicity...
June 15, 2017: Fitoterapia
https://www.readbyqxmd.com/read/28607169/cdc25a-is-a-critical-mediator-of-ischemic-neuronal-death-in-vitro-and-in-vivo
#13
Grace O Iyirhiaro, Doo Soon Im, Wassamon Boonying, Steve M Callaghan, Matthew J During, Ruth S Slack, David S Park
Dysregulation of cell cycle machinery is implicated in a number of neuronal death contexts, including stroke. Increasing evidence suggests that cyclin-dependent kinases (Cdks) are inappropriately activated in mature neurons under ischemic stress conditions. We previously demonstrated a functional role for the cyclin D1/Cdk4/pRb (retinoblastoma tumor suppressor protein) pathway in delayed neuronal death induced by ischemia. However, the molecular signals leading to cyclin D/Cdk4/pRb activation following ischemic insult are presently not clear...
July 12, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28598489/nicotinic-acetylcholine-receptor-mediated-protection-of-the-rat-heart-exposed-to-ischemia-reperfusion
#14
Spyros A Mavropoulos, Nayaab S Khan, Asaph C J Levy, Bradley T Faliks, Cristina P Sison, Valentin A Pavlov, Youhua Zhang, Kaie Ojamaa
Reperfusion injury following acute myocardial infarction is associated with significant morbidity. Activation of neuronal or non-neuronal cholinergic pathways in the heart has been shown to reduce ischemic injury and this effect has been attributed primarily to muscarinic acetylcholine receptors. In contrast, the role of nicotinic receptors, specifically alpha-7 subtype (α7nAChR) in the myocardium remains unknown which offers an opportunity to potentially repurpose several agonists/modulators that are currently under development for neurologic indications...
June 8, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28587341/histological-and-functional-assessment-of-the-efficacy-of-constraint-induced-movement-therapy-in-rats-following-neonatal-hypoxic-ischemic-brain-injury
#15
Hyunha Kim, Min Jae Kim, Young Soo Koo, Hae In Lee, Sae-Won Lee, Myung Jun Shin, Soo-Yeon Kim, Yong Beom Shin, Yong-Il Shin, Byung Tae Choi, Young Ju Yun, Hwa Kyoung Shin
Constraint-induced movement therapy (CIMT) is used in stroke rehabilitation to promote recovery of upper limb motor function. However, its efficacy in improving functional outcomes in children with hemiplegic cerebral palsy has not been clearly determined in clinical or experimental research. The aim of our study was to assess the efficacy of a new experimental model of CIMT, evaluated in terms of mortality, stress, motor and cognitive function in rats having undergone a neonatal hypoxic-ischemic (HI) brain injury...
June 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28580185/the-soluble-vegf-receptor-sflt-1-contributes-to-impaired-neovascularization-in-aged-mice
#16
Guangxian Zhao, Xian W Cheng, Limei Piao, Lina Hu, Yanna Lei, Guang Yang, Aiko Inoue, Shinyu Ogasawara, Hongxian Wu, Chang-Ning Hao, Kenji Okumura, Masafumi Kuzuya
The mechanism by which angiogenesis declines with aging is not fully understood. Soluble vascular endothelial growth factor receptor 1 (VEGFR1) form (sFlt1) contributes to endothelial dysfunction in pathological conditions. However, the roles of sFlt1 in ischemia-induced neovascularizationof aged animals have not been investigated. To study aging-related sFlt1 change and its impact on ischemia-induced neovascularization, a hindlimb ischemia model was applied to young and aged mice. Blood flow imaging assay revealed that the blood flow recovery remained impaired throughout the follow-up period...
May 2017: Aging and Disease
https://www.readbyqxmd.com/read/28571880/%C3%AE-tocopherol-especially-%C3%AE-tocopherol-phosphate-exerts-antiapoptotic-and-angiogenic-effects-on-rat-bone-marrow-derived-endothelial-progenitor-cells-under-high-glucose-and-hypoxia-conditions
#17
Ziheng Wu, Xiangtao Zheng, Luyang Meng, Xin Fang, Yangyan He, Donglin Li, Chengfei Zheng, Hongkun Zhang
OBJECTIVE: Considering the poor efficacy of local intramuscular injections with endothelial progenitor cells (EPCs) for critical limb ischemia in patients with diabetes, the study aimed to investigate the effect of α-tocopherol (α-T) and α-tocopherol phosphate (α-TP) on apoptosis and angiogenesis in a rat model under oxidative stress conditions. METHODS: Primary EPCs from Sprague-Dawley rats were harvested and treated with α-T and α-TP for 24 hours. Gene transcription and protein expression were evaluated by real-time polymerase chain reaction and Western blot, respectively...
May 29, 2017: Journal of Vascular Surgery
https://www.readbyqxmd.com/read/28539339/mif-2-d-dt-enhances-proximal-tubular-cell-regeneration-through-slpi-and-atf4-dependent-mechanisms
#18
Akinobu Ochi, Dong Chen, Wibke Schulte, Lin Leng, Nickolas Gilbert Moeckel, Marta Piecychna, Luisa Averdunk, Christian Stoppe, Richard Bucala, Gilbert W Moeckel
Macrophage migration inhibitory factor (MIF) is a cytokine with pleiotropic actions that is produced by several organs and cell types. Depending on the target cell and the inflammatory context, MIF can engage its two component receptor complex CD74 and CD44, and the chemokine receptors CXCR2/4. MIF is constitutively expressed in renal proximal tubular cells, stored in intracellular preformed pools and is released at a low rate. Recently a second MIF-like protein (i.e. MIF-2/D-DT) has been characterized in mammals...
May 24, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28536871/impact-of-early-subcultures-on-stemness-migration-and-angiogenic-potential-of-adipose-tissue-derived-stem-cells-and-their-resistance-to-in-vitro-ischemic-condition
#19
Hossein Faghih, Arash Javeri, Masoumeh Fakhr Taha
Adipose tissue-derived stem cells (ADSCs) are capable of multipotential differentiation and express several angiogenic, anti-apoptotic and immunomodulatory markers. These features make adipose tissue as a promising source of stem cells for regenerative medicine. However, for efficient translational use, culture-induced changes in the gene expression profile and resistance of the ADSCs to ischemic environment should be taken into consideration. We compared the expression of some clinically important markers between the unpassaged and third-passaged ADSCs by RT-PCR, qPCR and flow cytometry...
May 23, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28484701/dual-specificity-phosphatase-4-overexpression-in-cells-prevents-hypoxia-reoxygenation-induced-apoptosis-via-the-upregulation-of-enos
#20
Julie A Dougherty, Joanna Kilbane Myers, Mahmood Khan, Mark G Angelos, Chun-An Chen
Mitogen-activated protein kinases (MAPKs) signaling cascades regulate several cellular functions, including differentiation, proliferation, survival, and apoptosis. The duration and magnitude of phosphorylation of these MAPKs are decisive determinants of their physiological functions. Dual-specificity phosphatases exert kinetic control over these signaling cascades. Previously, we demonstrated that DUSP4(-/-) hearts sustain a larger infarct and have poor functional recovery, when isolated hearts were subjected to ischemia/reperfusion...
2017: Frontiers in Cardiovascular Medicine
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