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https://www.readbyqxmd.com/read/29214897/ss-31-peptide-enables-mitochondrial-targeting-drug-delivery-a-promising-therapeutic-alteration-to-prevent-hair-cell-damage-from-aminoglycosides
#1
Xiao Kuang, Shuang Zhou, Weiling Guo, Zhenjie Wang, Yanhui Sun, Hongzhuo Liu
Aminoglycoside-induced hearing loss stems from damage or loss of mechanosensory hair cells in the inner ear. Intrinsic mitochondrial cell death pathway plays a key role in that cellular dysfunction for which no proven effective therapies against oto-toxicities exist. Therefore, the aim of the present study was to develop a new mitochondrial targeting drug delivery system (DDS) that provided improved protection from gentamicin. Particularly, SS-31 peptide-conjugated geranylgeranylacetone (GGA) loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles were constructed successfully via emulsion-solvent evaporation method...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/29197632/crosstalk-between-autophagy-and-oxidative-stress-regulates-proteolysis-in-the-diaphragm-during-mechanical-ventilation
#2
Ashley J Smuder, Kurt J Sollanek, W Bradley Nelson, Kisuk Min, Erin E Talbert, Andreas N Kavazis, Matthew B Hudson, Marco Sandri, Hazel H Szeto, Scott K Powers
Mechanical ventilation (MV) results in the rapid development of ventilator-induced diaphragm dysfunction (VIDD). While the mechanisms responsible for VIDD are not fully understood, recent data reveal that prolonged MV activates autophagy in the diaphragm, which may occur as a result of increased cellular reactive oxygen species (ROS) production. Therefore, we tested the hypothesis that 1) accelerated autophagy is a key contributor to VIDD; and that 2) oxidative stress is required to increase the expression of autophagy genes in the diaphragm...
November 29, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/29156337/facile-preparation-of-core-cross-linked-nanomicelles-based-on-graft-copolymers-with-ph-responsivity-and-reduction-sensitivity-for-doxorubicin-delivery
#3
Tiandong Chen, Yi Xiao, Wei Lu, Shiyuan Liu, Lin Gan, Jiahui Yu, Jin Huang
To achieve passive targeting and controlled drug release at tumor sites trigged by low pH value and high level of glutathione (GSH), optimized delivery system for doxorubicin (DOX) based on core cross-linked nanomicelles was developed in this research. Particularly, methoxypoly(ethylene glycol)-nitrophenyl carbonate (mPEG-NPC) and 3,4-dihydroxyphenylaceticacid were grafted onto synthesized poly(N,N'-cystamine bisacrylamide-N-Boc-1,2-diaminoethane) (poly(CBA-DAE)) to give methoxypoly(ethylene glycol)-g-poly(N,N'-cystamine bisacrylamide-N-Boc-1, 2-diaminoethane)-g-3, 4-dihydroxyphenylaceticacid (mPEG-g-SS-PCD-DA)...
November 16, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/29132140/mitochondria-targeted-peptide-attenuates-mitochondrial-dysfunction-controls-inflammation-and-protects-against-spinal-cord-injury-induced-lung-injury
#4
Liu-Long Zhu, Mao-Qiang Li, Fan He, Shao-Bo Zhou, Wu Jiang
BACKGROUND/AIMS: Spinal cord injury (SCI) is a common and devastating disease, which results in systemic inflammatory response syndrome and secondary lung injury. Mitochondrial dysfunction and inflammation are closely related to lung injury in diverse disease models. No studies have demonstrated the effects of mitochondrial targeted peptide SS-31 in a mouse model of SCI-induced lung injury. METHODS: Immediately after injury, mice in the treatment groups received a daily, single-dose intraperitoneal injection of SS-31 and for the next 2 days...
November 13, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29120231/impact-of-clear-corneal-incision-morphology-on-incision-site-descemet-membrane-detachment-in-conventional-and-femtosecond-laser-assisted-phacoemulsification
#5
Jeewan S Titiyal, Manpreet Kaur, Priyanka Ramesh, Pooja Shah, Ruchita Falera, Lalit M S Bageshwar, Ashutosh Kinkar, Namrata Sharma
PURPOSE: To assess intraoperative morphology of clear corneal incisions (CCI) and its impact on incision-site descemet membrane detachment (DMD) in conventional phacoemulsification and femtosecond laser-assisted cataract surgery (FLACS). METHODS: Prospective comparative study of 129 eyes that underwent either conventional phacoemulsification (Group I, n = 77) or FLACS (Group II, n = 52) was undertaken at an apex tertiary care ophthalmic setup. In group I, a 2...
November 9, 2017: Current Eye Research
https://www.readbyqxmd.com/read/29017301/pelvic-incidence-can-be-changed-not-only-by-age-and-sex-but-also-by-posture-used-during-imaging
#6
Ji Won Moon, James Ki Shinn, Dalsung Ryu, Se-Yang Oh, Yu Shik Shim, Seung Hwan Yoon
OBJECTIVE: Computed tomography (CT), rather than conventional 2-dimensional radiography, was used to scan and measure pelvic parameters. The results were compared with measurements using X-ray. METHODS: Pelvic parameters were measured using both CT and X-ray in 254 patients who underwent both abdomino-pelvic CT and X-ray at the pelvic site. We assessed the similarity of the pelvic parameters between the 2 exams, as well as the correlations of pelvic parameters with sex and age...
September 2017: Korean Journal of Spine
https://www.readbyqxmd.com/read/28961281/chronic-administration-of-mitochondrion-targeted-peptide-ss-31-prevents-atherosclerotic-development-in-apoe-knockout-mice-fed-western-diet
#7
Meng Zhang, Hongting Zhao, Jing Cai, Huihui Li, Qi Wu, Tong Qiao, Kuanyu Li
BACKGROUND: Oxidative stress and inflammatory factors are deeply involved in progression of atherosclerosis. Mitochondrion-targeted peptide SS-31, selectively targeting to mitochondrial inner membrane reacting with cardiolipin, has been reported to inhibit ROS generation and mitigate inflammation. The present study was designed to investigate whether SS-31 could suppress the development of atherosclerosis in vivo. METHODS: Male ApoE-/- mice (8 weeks old) fed with Western diet were treated with normal saline or SS-31 (1 mg/kg/d or 3 mg/kg/d) through subcutaneous injection for 12 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28898446/contradictory-effects-of-mitochondria-and-non-mitochondria-targeted-antioxidants-on-hepatocarcinogenesis-by-altering-dna-repair
#8
Bibo Wang, Jing Fu, Ting Yu, An Xu, Wenhao Qin, Zhishi Yang, Yao Chen, Hongyang Wang
Conflicting effects of antioxidant supplementation on cancer prevention or promotion is of great concern to healthy people and cancer patients. Despite recent studies about antioxidants accelerating the progression of lung cancer and melanoma, it does not fully deny antioxidants for cancer prevention. Both tumor and antioxidants types influence the actual efficacy. However, little is known about the impact of different types of antioxidants on primary hepatocellular carcinoma (HCC), including non-mitochondrial- and mitochondrial-targeted antioxidants...
September 12, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28852135/peptide-ss-31-upregulates-frataxin-expression-and-improves-the-quality-of-mitochondria-implications-in-the-treatment-of-friedreich-ataxia
#9
Hongting Zhao, Huihui Li, Shuangying Hao, Jiping Chen, Jing Wu, Chuanhui Song, Meng Zhang, Tong Qiao, Kuanyu Li
Friedreich ataxia is a progressive neurodegenerative disease caused by the expansion of GAA trinucleotide repeats within the first intron of the FXN gene, which encodes frataxin. The pathophysiology of the disease is thought to be derived from the decrease of Fe-S cluster biogenesis due to frataxin deficiency. There is currently no effective treatment for the disease. In our study, we demonstrated that treatment with the mitochondrion-targeted peptide SS-31 reduced frataxin deficiency-induced oxidative stress in lymphoblasts and fibroblasts derived from patients...
August 29, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28830815/a-novel-mechanism-of-pre-transplant-insulin-resistance-contributing-to-post-transplant-complications-cyclosporin-a-induced-o-glcnacylation
#10
Xinghua Qin, Xiaoliang Li, Chuanming Liu, Ziwei Chen
Pre-transplant insulin resistance has been proved to be an important risk factor for organ transplantation, predicting increased post-transplant complications and worse survival outcomes. However, the underlying mechanism is still unclear. Cyclosporin A (CsA) is widely used as an immunosuppressant after organ transplantation, while emerging evidence has shown that CsA increases the risk of post-transplant complications. Thus, in this study, using a cellular model of palmitate-induced insulin resistance, we evaluate the effect of CsA on apoptosis in skeletal muscle C2C12 cells with palmitate-induced insulin resistance...
October 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28656516/targeting-mitochondrial-calcium-handling-and-reactive-oxygen-species-in-heart-failure
#11
REVIEW
Alexander Dietl, Christoph Maack
PURPOSE OF REVIEW: In highly prevalent cardiac diseases, new therapeutic approaches are needed. Since the first description of oxidative stress in heart failure, reactive oxygen species (ROS) have been considered as attractive drug targets. Though clinical trials evaluating antioxidant vitamins as ROS-scavenging agents yielded neutral results in patients at cardiovascular risk, the knowledge of ROS as pathophysiological factors has considerably advanced in the past few years and led to novel treatment approaches...
August 2017: Current Heart Failure Reports
https://www.readbyqxmd.com/read/28487636/elamipretide-ss-31-ameliorates-isoflurane-induced-long-term-impairments-of-mitochondrial-morphogenesis-and-cognition-in-developing-rats
#12
Jing Wu, Shuangying Hao, Xiao-Ru Sun, Hui Zhang, Huihui Li, Hongting Zhao, Mu-Huo Ji, Jian-Jun Yang, Kuanyu Li
Mitochondria are supposed to be involved in the early pathogenesis of general anesthesia (GA)-induced neurotoxicity and long-term cognitive deficits in developing brains. However, effective pharmacologic agents targeted on mitochondria during GA exposure are lacking. This study explores the protective effects of mitochondrion-targeted antioxidant elamipretide (SS-31) on mitochondrial morphogenesis and cognition in developing rats exposed to isoflurane. Rat pups at postnatal day (PND) 7 were exposed to 1.5% isoflurane for 6 h following intraperitoneal administration of elamipretide or vehicle with 30 min interval...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28322835/role-of-mitochondrial-dysfunction-in-renal-fibrosis-promoted-by-hypochlorite-modified-albumin-in-a-remnant-kidney-model-and-protective-effects-of-antioxidant-peptide-ss-31
#13
Hao Zhao, Yan-Jun Liu, Zong-Rui Liu, Dong-Dong Tang, Xiao-Wen Chen, Yi-Hua Chen, Ru-Ning Zhou, Si-Qi Chen, Hong-Xin Niu
Oxidative stress aggravates renal fibrosis, a pathway involved in almost all forms of chronic kidney disease (CKD). However, the underlying mechanism involved in the pathogenesis of renal oxidative stress has not been completely elucidated. In this study, we explored the role and mechanism of hypochlorite-modified albumin (HOCl-alb) in mediating oxidative stress and fibrotic response in a remnant-kidney rat model. Five-sixths nephrectomy (5/6 NX) was performed on the rats and then the animals were randomly assigned to intravenous treatment with either vehicle alone, or HOCl-rat serum albumin (RSA) in the presence or absence of SS-31 (administered intraperitoneally)...
June 5, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28063595/the-mitochondrial-targeted-peptide-ss-31-improves-glomerular-architecture-in-mice-of-advanced-age
#14
Mariya T Sweetwyne, Jeffrey W Pippin, Diana G Eng, Kelly L Hudkins, Ying Ann Chiao, Matthew D Campbell, David J Marcinek, Charles E Alpers, Hazel H Szeto, Peter S Rabinovitch, Stuart J Shankland
Although age-associated changes in kidney glomerular architecture have been described in mice and man, the mechanisms are unknown. It is unclear if these changes can be prevented or even reversed by systemic therapies administered at advanced age. Using light microscopy and transmission electron microscopy, our results showed glomerulosclerosis with injury to mitochondria in glomerular epithelial cells in mice aged 26 months (equivalent to a 79-year-old human). To test the hypothesis that reducing mitochondrial damage in late age would result in lowered glomerulosclerosis, we administered the mitochondrial targeted peptide, SS-31, to aged mice...
May 2017: Kidney International
https://www.readbyqxmd.com/read/27881606/mitochondria-protection-after-acute-ischemia-prevents-prolonged-upregulation-of-il-1%C3%AE-and-il-18-and-arrests-ckd
#15
Hazel H Szeto, Shaoyi Liu, Yi Soong, Surya V Seshan, Leona Cohen-Gould, Viacheslav Manichev, Leonard C Feldman, Torgny Gustafsson
The innate immune system has been implicated in both AKI and CKD. Damaged mitochondria release danger molecules, such as reactive oxygen species, DNA, and cardiolipin, which can cause NLRP3 inflammasome activation and upregulation of IL-18 and IL-1β It is not known if mitochondrial damage persists long after ischemia to sustain chronic inflammasome activation. We conducted a 9-month study in Sprague-Dawley rats after 45 minutes of bilateral renal ischemia. We detected glomerular and peritubular capillary rarefaction, macrophage infiltration, and fibrosis at 1 month...
May 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27855593/protective-effect-of-bendavia-ss-31-against-oxygen-glucose-deprivation-stress-induced-mitochondrial-damage-in-human-brain-microvascular-endothelial-cells
#16
Takahiko Imai, Keisuke Mishiro, Toshinori Takagi, Aoi Isono, Hideko Nagasawa, Kazuhiro Tsuruma, Masamitsu Shimazawa, Hideaki Hara
Mitochondria play a key role in cell survival by perfoming functions such as adenosine tri-phosphate (ATP) synthesis, regulation of apoptotic cell death, calcium storage. Hypoxic conditions induce mitochondrial dysfunction, which leads to endothelial injury in cerebral ischemia. Functional disorders include the following: collapse of mitochondrial membrane potential, reduction of ATP synthesis, and generation of reactive oxygen species (ROS). Bendavia, a novel tetra-peptide, has been reported to restrict the uncoupling of the mitochondrial membrane chain, protect the synthesis of ATP, and inhibit ROS generation...
2017: Current Neurovascular Research
https://www.readbyqxmd.com/read/27519664/protection-of-mitochondria-prevents-high-fat-diet-induced-glomerulopathy-and-proximal-tubular%C3%A2-injury
#17
Hazel H Szeto, Shaoyi Liu, Yi Soong, Nazia Alam, Glen T Prusky, Surya V Seshan
Obesity is a major risk factor for the development of chronic kidney disease, even independent of its association with hypertension, diabetes, and dyslipidemia. The primary pathologic finding of obesity-related kidney disease is glomerulopathy, with glomerular hypertrophy, mesangial matrix expansion, and focal segmental glomerulosclerosis. Proposed mechanisms leading to renal pathology include abnormal lipid metabolism, lipotoxicity, inhibition of AMP kinase, and endoplasmic reticulum stress. Here we report dramatic changes in mitochondrial structure in glomerular endothelial cells, podocytes, and proximal tubular epithelial cells after 28 weeks of a high-fat diet in C57BL/6 mice...
November 2016: Kidney International
https://www.readbyqxmd.com/read/27350953/mitochondria-targeted-antioxidant-ss-31-is-a-potential-novel-ophthalmic-medication-for-neuroprotection-in-glaucoma
#18
Yu Pang, Chao Wang, Ling Yu
Glaucoma is the second leading cause of irreversible blindness and a neurodegenerative disease with a complex pathogenesis. Increasing evidence suggests that oxidative stress and mitochondrial dysfunction have crucial roles in most neurodegenerative diseases such as glaucoma. The conventional clinical treatment for glaucoma is lowering the intraocular pressure (IOP). Some patients have normal IOP, whereas other patients appear to obtain adequate control of IOP after filtration surgery or medication. However, these patients still experience progressive visual field loss...
2015: Medical Hypothesis, Discovery and Innovation in Ophthalmology
https://www.readbyqxmd.com/read/27286183/effects-of-single-vs-multiple-sets-during-10-weeks-of-water-based-resistance-training-on-neuromuscular-adaptations-in-young-women
#19
RANDOMIZED CONTROLLED TRIAL
M C W Schoenell, C L Alberton, C L Tiggemann, M Noll, R Costa, N S Santos, L F M Kruel
This study aims to analyze the neuromuscular adaptations of sedentary young women between water-based resistance training performed with single and multiple sets. 66 women (24.72±4.33 years old) were randomly divided into 2 training groups: SS (single set of 30 s) and MS (3 sets of 30 s). Both groups performed 2 sessions per week for 10 weeks. One repetition maximal test (1RM), muscle endurance test (maximal repetitions at 60% 1RM) and muscle power test (squat and countermovement jump performance) were evaluated at pre- and post-training...
September 2016: International Journal of Sports Medicine
https://www.readbyqxmd.com/read/27188504/defective-postreperfusion-metabolic-recovery-directly-associates-with-incident-delayed-graft-function
#20
Leonie G M Wijermars, Alexander F Schaapherder, Dorottya K de Vries, Lars Verschuren, Rob C I Wüst, Sarantos Kostidis, Oleg A Mayboroda, Frans Prins, Jan Ringers, Jörgen Bierau, Jaap A Bakker, Teake Kooistra, Jan H N Lindeman
Delayed graft function (DGF) following kidney transplantation affects long-term graft function and survival and is considered a manifestation of ischemia reperfusion injury. Preclinical studies characterize metabolic defects resulting from mitochondrial damage as primary driver of ischemia reperfusion injury. In a comprehensive approach that included sequential establishment of postreperfusion arteriovenous concentration differences over the human graft, metabolomic and genomic analysis in tissue biopsies taken before and after reperfusion, we tested whether the preclinical observations translate to the context of clinical DGF...
July 2016: Kidney International
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