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https://www.readbyqxmd.com/read/29770487/inhibitory-effect-of-melatonin-on-necroptosis-via-repressing-the-ripk3-pgam5-cypd-mptp-pathway-attenuates-cardiac-microvascular-ischemia-reperfusion-injury
#1
Hao Zhou, Dandan Li, Pingjun Zhu, Qiang Ma, Toan Sam, Jin Wang, Shunying Hu, Yundai Chen, Yingmei Zhang
The molecular features of necroptosis in cardiac ischemia reperfusion (IR) injury have been extensively explored. However, there have been no studies investigating the physiological regulatory mechanisms of melatonin acting on necroptosis in cardiac IR injury. This study was designed to determine the role of necroptosis in microvascular IR injury, and investigate the contribution of melatonin in repressing necroptosis and preventing IR-mediated endothelial system collapse. Our results demonstrated that Ripk3 was primarily activated by IR injury and consequently aggravated endothelial necroptosis, microvessel barrier dysfunction, capillary hyperpermeability, the inflammation response, microcirculatory vasospasms and microvascular perfusion defects...
May 16, 2018: Journal of Pineal Research
https://www.readbyqxmd.com/read/29769744/nadph-ameliorates-mptp-induced-dopaminergic-neurodegeneration-through-inhibiting-p38mapk-activation
#2
Jing-Si Zhou, Zhou Zhu, Feng Wu, Ying Zhou, Rui Sheng, Jun-Chao Wu, Zheng-Hong Qin
Parkinson's disease (PD) is the second most common neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in substantia nigra pars compacta (SNpc). Although the pathogenic mechanism underlying PD remains largely unknown, decreased nigral glutathione (GSH) in postmortem brains of PD patients supports the presence of oxidative stress in PD. We found that Nicotinamide adenine dinucleotide phosphate (NADPH), which is important for maintaining the level of GSH, protected dopaminergic (DA) neurons from neurotoxicity of MPTP/MPP+ ...
May 16, 2018: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/29766336/ischaemic-preconditioning-protects-cardiomyocytes-from-anthracycline-induced-toxicity-via-the-pi3k-pathway
#3
Angshuman Maulik, Sean M Davidson, Izabela Piotrowska, Malcolm Walker, Derek M Yellon
PURPOSE: Anthracyclines cause chronic irreversible cardiac failure, but the mechanism remains poorly understood. Emerging data indicate that cardiac damage begins early, suggesting protective modalities delivered in the acute stage may confer prolonged benefit. Ischaemic preconditioning (IPC) activates the pro-survival reperfusion injury salvage kinase (RISK) pathway which involves PI3-kinase and MAPK/ERK1/2. METHODS: We investigated whether simulated IPC (sIPC), in the form of a sublethal exposure to a hypoxic buffer simulating ischaemic conditions followed by reoxygenation, protects primary adult rat cardiomyocytes against anthracycline-induced injury...
May 15, 2018: Cardiovascular Drugs and Therapy
https://www.readbyqxmd.com/read/29763919/inhalation-of-hydrogen-of-different-concentrations-ameliorates-spinal-cord-injury-in-mice-by-protecting-spinal-cord-neurons-from-apoptosis-oxidative-injury-and-mitochondrial-structure-damages
#4
Xiao Chen, Jin Cui, Xiao Zhai, Jun Zhang, Zhengrong Gu, Xin Zhi, Weizong Weng, Panpan Pan, Liehu Cao, Fang Ji, Zhiwei Wang, Jiacan Su
BACKGROUND/AIMS: Hydrogen selectively neutralizes reactive oxygen species (ROS) and ameliorates various ROS-induced injuries. Spinal cord injury (SCI) is a serious injury to the central nervous system, and secondary SCI is closely related to excessive ROS generation. We hypothesized that hydrogen inhalation ameliorates SCI, and the mechanism of action may be related to the protective effects of hydrogen against oxidative stress, apoptosis, and mitochondrial damage. METHODS: Mechanically injured spinal cord neurons were incubated with different concentrations of hydrogen in vitro...
May 10, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29763901/5-aminolevulinic-acid-mediated-sonodynamic-therapy-alleviates-atherosclerosis-via-enhancing-efferocytosis-and-facilitating-a-shift-in-the-th1-th2-balance-toward-th2-polarization
#5
Yang Yang, Yuanyuan Liu, Xi Chen, Jie Gong, Zhen Huang, Wei Wang, Yuanqi Shi, Yu Wang, Jianting Yao, Zhaoqian Shen, Zhen Tian, Hong Jin, Ye Tian
BACKGROUND/AIMS: We and other groups have demonstrated that 5-aminolevulinic acid (ALA)-mediated sonodynamic therapy (ALA-SDT) induces macrophage and foam cell apoptosis and stabilizes atherosclerosis (AS) plaques in animal models. Lymphocytes also play vital roles in the development of AS. The primary purpose of the present study was to investigate the effects of ALA-SDT on T helper (Th) cell fate and function, Th subset differentiation, and atherosclerotic lesion stability. METHODS: We utilized ALA-SDT on Western diet-fed apoE-/-mice in vivo and human Jurkat cells in vitro...
May 9, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29755536/preclinical-study-of-ibuprofen-loaded-transnasal-mucoadhesive-microemulsion-for-neuroprotective-effect-in-mptp-mice-model
#6
Surjyanarayan Mandal, Snigdha Das Mandal, Krishna Chuttani, Krutika K Sawant, Bharat Bhushan Subudhi
Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), showed very promising neuroprotection action, but it suffers from high first pass metabolism and limited ability to cross blood brain barrier. Severe gastric toxicity following oral administration further limits its utility. Hence, the aim of this study was to investigate whether ibuprofen loaded mucoadhesive microemulsion (MMEI) could enhance the brain uptake and could also protect the dopaminergic neurons from MPTP-mediated neural inflammation. In this work, ibuprofen loaded polycarbophil based mucoadhesive microemulsion (MMEI) was developed by using response surface methodology (RSM)...
2018: Iranian Journal of Pharmaceutical Research: IJPR
https://www.readbyqxmd.com/read/29755339/therapeutic-potential-of-a-prolyl-hydroxylase-inhibitor-fg-4592-for-parkinson-s-diseases-in-vitro-and-in-vivo-regulation-of-redox-biology-and-mitochondrial-function
#7
Xuan Li, Xin-Xin Cui, Ya-Jing Chen, Ting-Ting Wu, Huaxi Xu, Huiyong Yin, Yun-Cheng Wu
As the main transcription factor that regulates the cellular responses to hypoxia, Hypoxia-inducible factor-1α (HIF-1α) plays an important role in the pathogenesis of Parkinson's disease (PD). HIF-1α is normally degraded through ubiquitination after hydroxylation by prolyl hydroxylases (PHD). Emerging evidence has suggested that HIF PHD inhibitors (HIF-PHI) may have neuroprotective effects on PD through increasing HIF-1α levels. However, the therapeutic benefit of HIF-PHI for PD remains poorly explored due to the lack of proper clinical compounds and understanding of the underlying molecular mechanisms...
2018: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/29746847/csa-attenuates-compression-induced-nucleus-pulposus-mesenchymal-stem-cells-apoptosis-via-alleviating-mitochondrial-dysfunction-and-oxidative-stress
#8
Zhiliang Li, Songfeng Chen, Kaige Ma, Xiao Lv, Hui Lin, Binwu Hu, Ruijun He, Zengwu Shao
AIMS: This study aims to investigate the protective effects and potential mechanisms of cyclosporine A (CsA), which efficiently inhibits mitochondrial permeability transition pore (MPTP) opening, on compression-induced apoptosis of human nucleus pulposus mesenchymal stem cells (NP-MSCs). MATERIALS AND METHODS: Human NP-MSCs were subjected to various periods of 1.0 MPa compression. Cell viability was evaluated using cell counting kit-8 (CCK-8) assay. The cellular ultrastructure and ATP level were analyzed via transmission electron microscopy (TEM) and ATP detection kit respectively...
May 7, 2018: Life Sciences
https://www.readbyqxmd.com/read/29743549/human-cortex-spheroid-with-a-functional-blood-brain-barrier-for-high-throughput-neurotoxicity-screening-and-disease-modeling
#9
Goodwell Nzou, R T Wicks, E E Wicks, S A Seale, C H Sane, A Chen, S V Murphy, J D Jackson, A J Atala
The integral selectivity characteristic of the blood brain barrier (BBB) limits therapeutic options for many neurologic diseases and disorders. Currently, very little is known about the mechanisms that govern the dynamic nature of the BBB. Recent reports have focused on the development and application of human brain organoids developed from neuro-progenitor cells. While these models provide an excellent platform to study the effects of disease and genetic aberrances on brain development, they may not model the microvasculature and BBB of the adult human cortex...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29738369/cardioprotective-effects-of-metformin
#10
Christine Driver, Kayode Dominion Samuel Bamitale, Aniessa Kazi, Mehnaaz Olla, Annah Ntsoaki Nyane, Peter Mark Oroma Owira
Metformin, routinely used as first-line drug in the treatment of type 2 diabetes has been shown to have cardioprotective effects beyond its glycemic control. These have been attributed to increases in Akt concentrations and activation of protein kinases in the RISK pathways. which prevent the mitochondrial mPTP from opening and rupturing it and therefore protects myocyte viability. In myocardial infarction and subsequent reperfusion, metformin activation of AMPK promotes glycolysis and keeps the mPTP closed...
May 3, 2018: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/29735655/soluble-epoxide-hydrolase-plays-a-key-role-in-the-pathogenesis-of-parkinson-s-disease
#11
Qian Ren, Min Ma, Jun Yang, Risa Nonaka, Akihiro Yamaguchi, Kei-Ichi Ishikawa, Kenta Kobayashi, Shigeo Murayama, Sung Hee Hwang, Shinji Saiki, Wado Akamatsu, Nobutaka Hattori, Bruce D Hammock, Kenji Hashimoto
Parkinson's disease (PD) is characterized as a chronic and progressive neurodegenerative disorder, and the deposition of specific protein aggregates of α-synuclein, termed Lewy bodies, is evident in multiple brain regions of PD patients. Although there are several available medications to treat PD symptoms, these medications do not prevent the progression of the disease. Soluble epoxide hydrolase (sEH) plays a key role in inflammation associated with the pathogenesis of PD. Here we found that MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced neurotoxicity in the mouse striatum was attenuated by subsequent repeated administration of TPPU, a potent sEH inhibitor...
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29729479/palmitate-lipotoxicity-in-enteric-glial-cells-lipid-remodeling-and-mitochondrial-ros-are-responsible-for-cyt-c-release-outside-mitochondria
#12
Lara Macchioni, Maya Petricciuolo, Magdalena Davidescu, Katia Fettucciari, Paolo Scarpelli, Rita Vitale, Leonardo Gatticchi, Pierluigi Orvietani, Andrea Marchegiani, Pierfrancesco Marconi, Gabrio Bassotti, Angela Corcelli, Lanfranco Corazzi
Enteric glial cells (EGCs) are components of the enteric nervous system, an organized structure that controls gut functions. EGCs may be vulnerable to different agents, such as bacterial infections that could alter the intestinal epithelial barrier, allowing bacterial toxins and/or other agents possessing intrinsic toxic effect to access cells. Palmitate, known to exhibit lipotoxicity, is released in the gut during the digestion process. In this study, we investigated the lipotoxic effect of palmitate in cultured EGCs, with particular emphasis on palmitate-dependent intracellular lipid remodeling...
May 2, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29727730/dor-agonist-snc-80-exhibits-anti-parkinsonian-effect-via-downregulating-upr-oxidative-stress-signals-and-inflammatory-response-in-vivo
#13
Erfath Thanjeem Begum M, Dwaipayan Sen
The pathophysiology of Parkinson's disease exhibit imperative roles in unfolded protein response stress-induced oxidative stress and inflammation in general. Although, delta opioid receptor (DOR), has been found to represent anti-parkinsonian effect at behavioral level, its underlying mechanism remains elusive till date. In the present study the role of DOR agonist, SNC-80 and the consorted molecular mechanisms, which translates to behavioral recuperation, has been delineated. In order to mimic PD, mice were intra-peritoneally injected with MPTP, following exposure to SNC-80 and L-DOPA to elucidate amelioration of the MPTP-induced behavioral impairments...
May 1, 2018: Neuroscience Letters
https://www.readbyqxmd.com/read/29722326/intracerebroventricularly-administered-1-methyl-4-phenylpyridinium-ion-and-brain-derived-neurotrophic-factor-affect-catecholaminergic-nerve-terminals-and-neurogenesis-in-the-hippocampus-striatum-and-substantia-nigra
#14
Jun-Fang Chen, Man Wang, Ying-Han Zhuang, Thomas Behnisch
Parkinson's disease is a progressive neurological disease characterized by the degeneration of dopaminergic neurons in the substantia nigra. A highly similar pattern of neurodegeneration can be induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 1-methyl-4-phenylpyridinium ion (MPP+ ), which cause the death of dopaminergic neurons. Administration of MPTP or MPP+ results in Parkinson's disease-like symptoms in rodents. However, it remains unclear whether intracerebroventricular MPP+ administration affects neurogenesis in the substantia nigra and subgranular zone or whether brain-derived neurotrophic factor alters the effects of MPP+ ...
April 2018: Neural Regeneration Research
https://www.readbyqxmd.com/read/29721078/localized-delivery-of-curcumin-into-brain-with-polysorbate-80-modified-cerasomes-by-ultrasound-targeted-microbubble-destruction-for-improved-parkinson-s-disease-therapy
#15
Nisi Zhang, Fei Yan, Xiaolong Liang, Manxiang Wu, Yuanyuan Shen, Min Chen, Yunxue Xu, Guangyang Zou, Peng Jiang, Caiyun Tang, Hairong Zheng, Zhifei Dai
Rationale: Treatment for Parkinson's disease (PD) is challenged by the presence of the blood-brain barrier (BBB) that significantly limits the effective drug concentration in a patient's brain for therapeutic response throughout various stages of PD. Curcumin holds the potential for α-synuclein clearance to treat PD; however, its applications are still limited due to its low bioavailability and poor permeability through the BBB in a free form. Methods: Herein, this paper fabricated curcumin-loaded polysorbate 80-modified cerasome (CPC) nanoparticles (NPs) with a mean diameter of ~110 nm for enhancing the localized curcumin delivery into the targeted brain nuclei via effective BBB opening in combination with ultrasound-targeted microbubble destruction (UTMD)...
2018: Theranostics
https://www.readbyqxmd.com/read/29717349/the-release-of-cytochrome-c-and-the-regulation-of-the-programmed-cell-death-progress-in-the-endosperm-of-winter-wheat-triticum-aestivum-l-under-waterlogging
#16
Yuan-Hong Qi, Fang-Fang Mao, Zhu-Qing Zhou, Dong-Cheng Liu, Min-Yu, Xiang-Yi Deng, Ji-Wei Li, Fang-Zhu Mei
It has been shown in mammalian systems that the mitochondria can play a key role in the regulation of apoptosis by releasing intermembrane proteins (such as cytochrome c) into the cytosol. Cytochrome c released from the mitochondria to the cytoplasm activates proteolytic enzyme cascades, leading to specific nuclear DNA degradation and cell death. This pathway is considered to be one of the important regulatory mechanisms of apoptosis. Previous studies have shown that endosperm cell development in wheat undergoes specialized programmed cell death (PCD) and that waterlogging stress accelerates the PCD process; however, little is known regarding the associated molecular mechanism...
May 2, 2018: Protoplasma
https://www.readbyqxmd.com/read/29714132/mir-7-replacement-therapy-in-parkinson-s-disease
#17
Ricardo Titze-de-Almeida, Simoneide Souza Titze-de-Almeida
The present review examines whether the microRNA 7 (miR-7) holds potential for slowing Parkinson's disease (PD) progression. First, the accurate expression of miR-7 allows for the normal development, physiology, and neurogenesis in the central nervous system, also keeping alpha-synuclein (α-Syn) at the physiological level. Second, patients with PD and parkinsonian MPTP-induced animals exhibit a significant decrease of miR-7 in brain areas associated with dopaminergic neurodegeneration. Depletion of miR-7 in the substantia nigra of clinical samples was related to α-Syn accumulation, loss of dopaminergic cells, and reduction of dopamine in the striatum...
April 30, 2018: Current Gene Therapy
https://www.readbyqxmd.com/read/29710533/thymoquinone-alleviates-arsenic-induced-hippocampal-toxicity-and-mitochondrial-dysfunction-by-modulating-mptp-in-wistar-rats
#18
Fakiha Firdaus, Mohd Faraz Zafeer, Mohammad Waseem, Rizwan Ullah, Masood Ahmad, Mohammad Afzal
Arsenic is a pervasive environmental pollutant that is found in ground waters globally and is related to numerous morbidities in the high-risk population areas in countries including Bangladesh, India, and the USA. Arsenic exposure has been ubiquitously reported for exacerbating free radical generation, mitochondrial dysfunction, and apoptosis by interfering with the mPTP functioning. Over the past decades, nutraceuticals with antioxidant properties have shown promising efficacy in arsenic poisoning. In the present study, we have examined, the protective efficacy of thymoquinone (TQ), an active component of seed oil of Nigella sativa with antioxidant and anti-inflammatory activity on arsenic-induced toxicity in hippocampi of Wistar rats...
April 4, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29705943/critical-contribution-of-ripk1-mediated-mitochondrial-dysfunction-and-oxidative-stress-to-compression-induced-rat-nucleus-pulposus-cells-necroptosis-and-apoptosis
#19
Songfeng Chen, Xiao Lv, Binwu Hu, Lei Zhao, Shuai Li, Zhiliang Li, Xiangcheng Qing, Hongjian Liu, Jianzhong Xu, Zengwu Shao
The aim of this study was to investigate whether RIPK1 mediated mitochondrial dysfunction and oxidative stress contributed to compression-induced nucleus pulposus (NP) cells necroptosis and apoptosis, together with the interplay relationship between necroptosis and apoptosis in vitro. Rat NP cells underwent various periods of 1.0 MPa compression. To determine whether compression affected mitochondrial function, we evaluated the mitochondrial membrane potential, mitochondrial permeability transition pore (mPTP), mitochondrial ultrastructure and ATP content...
April 28, 2018: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/29699003/-the-comparison-of-neurobehavioral-changes-and-impaired-locations-between-the-mouse-model-of-manganism-and-parkinson-s-disease
#20
C S Dou, C N Zhi, W L Liu, J L Fu, B Y Yao
Objective: To investigate the effect of manganese chloride (MnCl(2)) or 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) on the neurobehavioral and histopathology in C57BL/6 mice and provide evidence for the diagnosis, treatment and prevention of manganism. Methods: Adult male C57BL/6 mice were treated with MnCl(2) and MPTP respectively by intraperitoneal injection at the doses of 5, 10, 20mg Mn/kg and 30mg MPTP/kg. Controls were injected equivalent normal saline. All animals were administrated 5 times a week for 4 consecutive weeks and sacrificed after behavior tests on the fifth week...
February 20, 2018: Chinese Journal of Industrial Hygiene and Occupational Diseases
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