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https://www.readbyqxmd.com/read/28214632/synthesis-of-new-heterocyclic-compounds-based-on-pyrazolopyridine-scaffold-and-evaluation-of-their-neuroprotective-potential-in-mpp-induced-neurodegeneration
#1
Jabrane Jouha, Mohammed Loubidi, Jamila Bouali, Salha Hamri, Abderrafia Hafid, Franck Suzenet, Gérald Guillaumet, Taner Dagcı, Mostafa Khouili, Fadime Aydın, Luciano Saso, Güliz Armagan
Neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and Huntington's disease affect millions of people in the world. Thus several new approaches to treat brain disorders are under development. The aim of the present study is to synthesize potential neuroprotective heterocyclic compounds based on pyrazolopyridine derivatives and then to evaluate their effects in MPP(+)-induced neurodegeneration in human neuroblastoma cell line (SH-SY5Y cells). The effects of the compounds on cell viability were measured by MTT assay and the changes in apoptosis-related proteins including bax, Bcl-2, Bcl-xl and caspase-3 were investigated by western blot technique...
February 11, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28214472/bmp-12-activates-tenogenic-pathway-in-human-adipose-stem-cells-and-affects-their-immunomodulatory-and-secretory-properties
#2
Weronika Zarychta-Wiśniewska, Anna Burdzinska, Agnieszka Kulesza, Kamila Gala, Beata Kaleta, Katarzyna Zielniok, Katarzyna Siennicka, Marek Sabat, Leszek Paczek
BACKGROUND: Cell-based therapy is a treatment method in tendon injuries. Bone morphogenic protein 12 (BMP-12) possesses tenogenic activity and was proposed as a differentiating factor for stem cells directed to transplantation. However, BMPs belong to pleiotropic TGF-β superfamily and have diverse effect on cells. Therefore, the aim of this study was to determine if BMP-12 induces tenogenic differentiation of human adipose stem cells (hASCs) and how it affects other features of this population...
February 18, 2017: BMC Cell Biology
https://www.readbyqxmd.com/read/28214077/new-homoisoflavonoid-analogues-protect-cells-by-regulating-autophagy
#3
Li-She Gan, Lin-Wei Zeng, Xiang-Rong Li, Chang-Xin Zhou, Jie Li
As a special group of naturally occurring flavonoids, homoisoflavonoids have been discovered as active components of several traditional Chinese medicines for nourishing heart and mind. In this study, twenty homoisoflavonoid analogues, including different substitution groups on rings A and B, as well as heteroaromatic B ring, were synthesized and evaluated for their cardioprotective and neuroprotective activities. In a H2O2-induced H9c2 cardiomyocytes injury assay, nine homoisoflavonoid analogues showed promising activities in the same level as the positive control, diazoxide...
February 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28212331/analysis-of-epidermal-growth-factor-receptor-related-gene-expression-changes-in-a-cellular-and-animal-model-of-parkinson-s-disease
#4
In-Su Kim, Sushruta Koppula, Shin-Young Park, Dong-Kug Choi
We employed transcriptome analysis of epidermal growth factor receptor related gene expression changes in cellular and animal models of Parkinson's disease (PD). We used a well-known Parkinsonian toxin 1-methyl-4-phenylpyridine (MPP⁺) to induce neuronal apoptosis in the human neuroblastoma SH-SY5Y cell line. The MPP⁺-treatment of SH-SY5Y cells was capable of inducing neuro-apoptosis, but it remains unclear what kinds of transcriptional genes are affected by MPP⁺ toxicity. Therefore the pathways that were significantly perturbed in MPP⁺ treated human neuroblastoma SH-SY5Y cells were identified based on genome-wide gene expression data at two time points (24 and 48 h)...
February 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28187263/tetrahydroxystilbene-glucoside-inhibits-%C3%AE-synuclein-aggregation-and-apoptosis-in-a53t-%C3%AE-synuclein-transfected-cells-exposed-to-mpp-sup-sup
#5
Ruyi Zhang, Fangling Sun, Lan Zhang, Xuejing Sun, Lin Li
Increasing evidence has solidified the involvement of α-synuclein (α-Syn) and neurotoxins in the pathogenesis of Parkinson's disease (PD), suggesting a combination of genetic and environmental influences. 2,3,5,4'-Tetrahydroxystilbene -2-O-β-D-glucoside (TSG) is one of the main active components extracted from Polygonum multiflorum. The purpose of the present study was to investigate the effects of TSG on α-Syn aggregation, mitochondrial dysfunction, oxidative stress and apoptosis in vitro. A53T mutant α-synuclein-transfected cells (A53T AS cells) plus MPP+<sup></sup> exposure were used as a complex cell model of PD...
February 10, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28185818/amentoflavone-protects-dopaminergic-neurons-in-mptp-induced-parkinson-s-disease-model-mice-through-pi3k-akt-and-erk-signaling-pathways
#6
Qin Cao, Liyue Qin, Fei Huang, Xiaoshuang Wang, Liu Yang, Hailian Shi, Hui Wu, Beibei Zhang, Ziyu Chen, Xiaojun Wu
Parkinson's disease (PD) is characterized by the progressive degeneration of dopaminergic neurons in substantia nigra pars compacta (SNpc). Mitochondrial dysfunction and cell apoptosis are suggested to be actively involved in the pathogenesis of PD. In the present study, the neuroprotective effect of amentoflavone (AF), a naturally occurring biflavonoid from Selaginella tamariscina, was examined in PD models both in vitro and in vivo. On SH-SY5Y cells, AF treatment dose-dependently reduced 1-methyl-4-phenylpyridinium (MPP(+))-induced nuclear condensation and loss of cell viability without obvious cytotoxicity...
February 6, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28176804/griseofulvin-impairs-intraerythrocytic-growth-of-plasmodium-falciparum-through-ferrochelatase-inhibition-but-lacks-activity-in-an-experimental-human-infection-study
#7
Clare M Smith, Ante Jerkovic, Thy Thuc Truong, Simon J Foote, James S McCarthy, Brendan J McMorran
Griseofulvin, an orally active antifungal drug used to treat dermatophyte infections, has a secondary effect of inducing cytochrome P450-mediated production of N-methyl protoporphyrin IX (N-MPP). N-MPP is a potent competitive inhibitor of the heme biosynthetic-enzyme ferrochelatase, and inhibits the growth of cultured erythrocyte stage Plasmodium falciparum. Novel drugs against Plasmodium are needed to achieve malaria elimination. Thus, we investigated whether griseofulvin shows anti-plasmodial activity. We observed that the intraerythrocytic growth of P...
February 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28168426/mitochondrial-metabolism-regulates-microtubule-acetylome-and-autophagy-trough-sirtuin-2-impact-for-parkinson-s-disease
#8
Ana R Esteves, Daniela M Arduíno, Diana F Silva, Sofia D Viana, Frederico C Pereira, Sandra M Cardoso
Alterations in microtubule-dependent transport, mitochondrial dysfunction, and autophagic pathology are involved in neurodegeneration observed in sporadic Parkinson's disease. However, the mechanistic link connecting these events remains elusive. We observed that NAD(+) metabolism is altered in sporadic Parkinson's disease patient-derived cells, which contributes to Sirtuin-2 activation and subsequent decrease in acetylated-α-tubulin levels. Pharmacological inhibition of sirtuin-2 deacetylase activity selectively enhanced α-tubulin acetylation and facilitated the trafficking and clearance of misfolded proteins...
February 6, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28161643/sirt3-deacetylated-and-increased-citrate-synthase-activity-in-pd-model
#9
Xin-Xin Cui, Xuan Li, Su-Yan Dong, Yan-Jie Guo, Te Liu, Yun-Cheng Wu
SIRT3 have been found to be neuroprotective in many neurological diseases, but its detail mechanism is only partially understood. In this study, MPP(+) was used to treat SH-SY5Y cells as the cellular model of PD to test the role of SIRT3 and the mechanism may be involved in. We focused on the changes and relationship between SIRT3 and the key mitochondrial enzymes citrate synthase (CS) and isocitrate dehydrogenase 2 (IDH2). We found MPP(+) decreased SIRT3 expression. And our results showed that the enzymatic activities of CS and IDH2 were significantly reduced in MPP(+) treatment cells, while protein acetylation of CS and IDH2 increased...
February 2, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28151476/regulation-of-glutamate-transporter-trafficking-by-nedd4-2-in-a-parkinson-s-disease-model
#10
Yunlong Zhang, Xiaoliang He, Xingjun Meng, Xiaojuan Wu, Huichun Tong, Xiuping Zhang, Shaogang Qu
Glutamate transporters play a key role in glutamate clearance and protect the central nervous system from glutamate excitotoxicity. Dysfunctional glutamate transporters contribute to the pathogenesis of Parkinson's disease (PD); however, the mechanisms that underlie the regulation of glutamate transporters in PD are still not well characterized. Here we report that Nedd4-2 mediates the ubiquitination of glutamate transporters in 1-methyl-4- phenylpyridinium (MPP(+))-treated astrocytes and in the midbrain of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP)-constructed PD model mice...
February 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28144826/neuroprotective-effects-and-mechanisms-of-action-of-multifunctional-agents-targeting-free-radicals-monoamine-oxidase-b-and-cholinesterase-in-parkinson-s-disease-model
#11
Zheng Liu, Wei Cai, Ming Lang, Ruizuo Yan, Zhenshen Li, Gaoxiao Zhang, Pei Yu, Yuqiang Wang, Yewei Sun, Zaijun Zhang
Parkinson's disease (PD) is a complex neurodegenerative disorder with multifactorial pathologies, including progressive loss of dopaminergic (DA) neurons, oxidative stress, mitochondrial dysfunction, and increased monoamine oxidase (MAO) enzyme activity. There are currently only a few agents approved to ameliorate the symptoms of PD; however, no agent is able to reverse the progression of the disease. Due to the multifactorial pathologies, it is necessary to develop multifunctional agents that can affect more than one target involved in the disease pathology...
January 31, 2017: Journal of Molecular Neuroscience: MN
https://www.readbyqxmd.com/read/28141910/the-mechanism-of-valproic-acid-induced-fanconi-syndrome-involves-mitochondrial-dysfunction-and-oxidative-stress-in-rat-kidney
#12
Reza Heidari, Faezeh Jafari, Forouzan Khodaei, Babak Shirazi Yeganeh, Hossein Niknahad
AIM: Drug-induced kidney proximal tubular injury and renal failure (Fanconi syndrome; FS) is a clinical complication. Valproic acid (VPA) is among the FS-inducing drugs. The current investigation was designed to evaluate the role of mitochondrial dysfunction and oxidative stress in VPA-induced renal injury. METHODS: Animals received VPA (250 and 500 mg/kg, i.p., 15 consecutive days). Serum biomarkers of kidney injury and markers of oxidative stress were assessed...
January 31, 2017: Nephrology
https://www.readbyqxmd.com/read/28131852/interaction-of-pharmaceutical-excipients-with-organic-cation-transporters
#13
Sirima Soodvilai, Sunhapas Soodvilai, Varanuj Chatsudthipong, Tanasait Ngawhirunpat, Theerasak Rojanarata, Praneet Opanasopit
Increasing evidences have shown that many pharmaceutical excipients are not pharmacologically inert but instead have effects on several transport function of uptake and efflux drug transporters. Herein, we investigated whether the excipients frequently used in many drug formulations affect transport function of organic cation transporters (OCTs) that are responsible for elimination of cationic drugs. Our finding revealed that solubilizing agents, Tweens, showed the most significant effect rbOCT1/2-mediated [(3)H]-MPP(+) uptake in heterologous expressing cells...
January 25, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28123575/anti-tumor-and-anti-invasion-effects-of-a-combination-of-4-methylumbelliferone-and-ionizing-radiation-in-human-fibrosarcoma-cells
#14
Ryo Saga, Satoru Monzen, Mitsuru Chiba, Hironori Yoshino, Toshiya Nakamura, Yoichiro Hosokawa
Hyaluronan (HA) is a major component of the extracellular matrix that is synthesized in excess in cancer tissues. 4-methylumbelliferone (MU) inhibits the synthesis of HA and is closely related to the invasion and metastasis of cancer. However, the effects of MU in conjunction with cancer radiotherapy remain unknown. The present study assessed the anti-tumor and anti-invasion effects of the concomitant use of ionizing radiation (IR) and 100 µM MU on human fibrosarcoma HT1080 cells. Cell viability and cellular invasion potency assays were performed...
January 2017: Oncology Letters
https://www.readbyqxmd.com/read/28122942/comparative-analysis-of-mitochondrial-n-termini-from-mouse-human-and-yeast
#15
Sarah E Calvo, Olivier Julien, Karl R Clauser, Hongying Shen, Kimberli J Kamer, James A Wells, Vamsi K Mootha
The majority of mitochondrial proteins are encoded in the nuclear genome, translated in the cytoplasm, and directed to the mitochondria by a N-terminal presequence that is cleaved upon import. Recently, N-proteome catalogs have been generated for mitochondria from yeast and from human U937 cells. Here we applied the subtiligase method to determine N-termini for 327 proteins in mitochondria isolated from mouse liver and kidney. Comparative analysis between mitochondrial N-termini from mouse, human, and yeast proteins shows that while presequences are poorly conserved at the sequence level, other presequence properties are extremely conserved including a length of ~20-60aa, a net charge between +3 to +6, and the presence of stabilizing amino acids at the N-termini of mature proteins that follows the N-end rule from bacteria...
January 25, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28121982/activin-a-inhibits-mptp-and-lps-induced-increases-in-inflammatory-cell-populations-and-loss-of-dopamine-neurons-in-the-mouse-midbrain-in-vivo
#16
Sandy Stayte, Peggy Rentsch, Anna R Tröscher, Maximilian Bamberger, Kong M Li, Bryce Vissel
Parkinson's disease is a chronic neurodegenerative disease characterized by a significant loss of dopaminergic neurons within the substantia nigra pars compacta region and a subsequent loss of dopamine within the striatum. A promising avenue of research has been the administration of growth factors to promote the survival of remaining midbrain neurons, although the mechanism by which they provide neuroprotection is not understood. Activin A, a member of the transforming growth factor β superfamily, has been shown to be a potent anti-inflammatory following acute brain injury and has been demonstrated to play a role in the neuroprotection of midbrain neurons against MPP+-induced degeneration in vitro...
2017: PloS One
https://www.readbyqxmd.com/read/28118501/immunoglobulin-a-and-nutrients-in-milk-from-great-apes-throughout-lactation
#17
Miriam Garcia, Michael L Power, Kasey M Moyes
: Differences in macronutrients between human and ape milks appear relatively small, but variation in other components such as immunoglobulins (Ig) may be greater. This study characterized the macronutrient and secretory (sIgA) profiles in milk from gorillas and orangutans throughout lactation. Fifty-three milk samples from four gorillas and three orangutans were collected throughout 48 and 22 months postpartum (MPP), respectively. Samples were grouped in five stages of lactation (0 to 6 months, more than 6 months to 12 months, more than 12 months to 18 months, more than 18 months to 36 months, and more than 36 months to 48 months)...
March 2017: American Journal of Primatology
https://www.readbyqxmd.com/read/28114431/jump-squat-and-half-squat-exercises-selective-influences-on-speed-power-performance-of-elite-rugby-sevens-players
#18
Irineu Loturco, Lucas A Pereira, José E Moraes, Katia Kitamura, César C Cal Abad, Ronaldo Kobal, Fábio Y Nakamura
The aim of this study was to evaluate the relation between the maximum mean propulsive power (MPP) obtained in the loaded jump squat (JS) and half squat (HS) exercises and functional performances in vertical jumps, 40 m linear speed (VEL) and change-of-direction (COD) tests, using the median split technique. Twenty-two male rugby sevens players from the Brazilian National Olympic Team (Rio-2016) performed vertical jumping tests (squat and countermovement jumps [SJ and CMJ]), JS and HS exercises, COD speed test and sprinting velocity in 40 m, in this order...
2017: PloS One
https://www.readbyqxmd.com/read/28109635/impact-of-high-cholesterol-in-a-parkinson-s-disease-model-prevention-of-lysosomal-leakage-versus-stimulation-of-%C3%AE-synuclein-aggregation
#19
Ida Eriksson, Sangeeta Nath, Per Bornefall, Ana Maria Villamil Giraldo, Karin Öllinger
Parkinson's disease is characterized by accumulation of intraneuronal cytoplasmic inclusions, Lewy bodies, which mainly consist of aggregated α-synuclein. Controversies exist as to whether high blood cholesterol is a risk factor for the development of the disease and whether statin treatment could have a protective effect. Using a model system of BE(2)-M17 neuroblastoma cells treated with the neurotoxin 1-methyl-4-phenylpyridinium (MPP(+)), we found that MPP(+)-induced cell death was accompanied by cholesterol accumulation in a lysosomal-like pattern in pre-apoptotic cells...
January 16, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28108381/metabolomic-study-of-the-intervention-effects-of-shuihonghuazi-formula-a-traditional-chinese-medicinal-formulae-on-hepatocellular-carcinoma-hcc-rats-using-performance-hplc-esi-tof-ms
#20
Yongrui Bao, Shuai Wang, Xinxin Yang, Li Tianjiao, Mingyue Xia, Xiansheng Meng
ETHNOPHARMACOLOGICAL RELEVANCE: Metabolomics is the comprehensive assessment of endogenous metabolites of a biological system in a holistic context, and its property consists with the global view of Traditional Chinese Medicine (TCM). Shuihonghuazi Formula (SHHZF) has been used for liver cancer early treatment in clinical for more than thirty years, but its mechanism remains unclear completely. This paper was designed to explore the therapeutic effects of SHHZF on liver cancer and its metabolomic characters...
January 17, 2017: Journal of Ethnopharmacology
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