المؤلفون: He M; Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032 Shaanxi, China., Long P; Department of Ophthalmology, The General Hospital of Western Theater Command, Chengdu, 610083 Sichuan, China., Chen T; Center of Clinical Aerospace Medicine, Fourth Military Medical University, Xi'an, 710032 Shaanxi, China., Li K; Experiment Teaching Center, Fourth Military Medical University, Xi'an, 710032 Shaanxi, China., Wei D; Center of Clinical Aerospace Medicine, Fourth Military Medical University, Xi'an, 710032 Shaanxi, China., Zhang Y; The Air Force Hospital from Northern Theater PLA, Shenyang, 110092 Liaoning, China., Wang W; Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032 Shaanxi, China., Hu Y; Clinical Medical College & Affiliated Hospital of Chengdu University, Chengdu, 610081 Sichuan, China., Ding Y; Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032 Shaanxi, China., Wen A; Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032 Shaanxi, China.

المصدر: Oxidative medicine and cellular longevity [Oxid Med Cell Longev] 2021 Oct 23; Vol. 2021, pp. 1641717. Date of Electronic Publication: 2021 Oct 23 (Print Publication: 2021).

نوع المنشور: Journal Article; Observational Study

بيانات الدورية: Publisher: Hindawi Pub. Corp Country of Publication: United States NLM ID: 101479826 Publication Model: eCollection Cited Medium: Internet ISSN: 1942-0994 (Electronic) Linking ISSN: 19420994 NLM ISO Abbreviation: Oxid Med Cell Longev Subsets: MEDLINE

مواضيع طبية MeSH: Oxidative Stress*, Aldehyde Dehydrogenase, Mitochondrial/*metabolism , Diabetes Mellitus, Experimental/*complications , Diabetes Mellitus, Type 1/*complications , Diabetes Mellitus, Type 2/*complications , Diabetic Retinopathy/*etiology , Reactive Oxygen Species/*metabolism , Retina/*enzymology , Sirtuin 1/*metabolism, Adult ; Aldehyde Dehydrogenase, Mitochondrial/genetics ; Animals ; Diabetes Mellitus, Experimental/enzymology ; Diabetes Mellitus, Experimental/genetics ; Diabetes Mellitus, Type 1/enzymology ; Diabetes Mellitus, Type 1/genetics ; Diabetes Mellitus, Type 2/enzymology ; Diabetes Mellitus, Type 2/genetics ; Diabetic Retinopathy/enzymology ; Diabetic Retinopathy/genetics ; Disease Models, Animal ; Disease Progression ; Female ; Humans ; Male ; Middle Aged ; Rats, Sprague-Dawley ; Retina/pathology ; Retrospective Studies ; Rats

مستخلص: Clinical observations found vision-threatening diabetic retinopathy (DR) occurs in both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) patients, but T1DM may perform more progressive retinal abnormalities at the same diabetic duration with or without clinical retinopathy. In the present study, T1DM and T2DM patients without manifestations of DR were included in our preliminary clinical retrospective observation study to investigate the differentiated retinal function at the preclinical stage. Then, T1DM and T2DM rat models with 12-week diabetic duration were constructed to explore the potential mechanism of the discrepancy in retinal disorders. Our data demonstrated T1DM patients presented a poor retinal function, a higher allele frequency for ALDH2GA/AA, and a depressed aldehyde dehydrogenase 2 (ALDH2) activity and silent information regulator 1 (SIRT1) level, compared to T2DM individuals. In line with this, higher amplitudes of neurovascular function-related waves of electroretinograms were found in T2DM rats. Furthermore, the retinal outer nuclear layers were reduced in T1DM rats. The levels of retinal oxidative stress biomarkers including total reactive oxygen species, NADPH oxidase 4 and mitochondrial DNA damage, and inflammatory indicators covering inducible/endothelial nitric acid synthase ratio, interleukin-1, and interleukin-6 were obviously elevated. Notably, the level of retinal ALDH2 and SIRT1 in T1DM rats was significantly diminished, while the expression of neovascularization factors was dramatically enhanced compared to T2DM. Together, our data indicated that the ALDH2/SIRT1 deficiency resulted in prominent oxidative stress and was in association with DR progression. Moreover, a differentiating ALDH2/SIRT1 expression may be responsible for the dissimilar severity of DR pathological processes in chronic inflammatory-related T1DM and T2DM.
Competing Interests: All authors have read the journal's policy on authorship agreement and conflict of interest. The authors have declared that no conflict of interest exists.
(Copyright © 2021 Mengshan He et al.)

المؤلفون: Long P; Department of General Practice, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.; Department of Ophthalmology, The General Hospital of Western Theater Command, Chengdu 610083, Sichuan Province, China.; Center of Clinical Aerospace Medicine, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China., He M; Department of Chinese Material Medical and Natural Medicines, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.; Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China., Yan W; Department of Ophthalmology, The 900th Hospital of Joint Logistic Support Force, PLA (Clinical Medical College of Fujian Medical University, Dongfang Hospital Affiliated to Xiamen University), Fuzhou 350025, Fujian Province, China., Chen W; Department of General Practice, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China., Wei D; Center of Clinical Aerospace Medicine, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.; Department of Aviation Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China., Wang S; Department of Chinese Material Medical and Natural Medicines, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China., Zhang Z; Center of Clinical Aerospace Medicine, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.; Department of Aviation Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China., Ge W; Department of General Practice, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China., Chen T; Center of Clinical Aerospace Medicine, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.; Department of Aviation Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, Shaanxi Province, China.

المصدر: Aging [Aging (Albany NY)] 2020 Dec 19; Vol. 13 (2), pp. 2750-2767. Date of Electronic Publication: 2020 Dec 19.

نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't

بيانات الدورية: Publisher: Impact Journals, LLC Country of Publication: United States NLM ID: 101508617 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1945-4589 (Electronic) Linking ISSN: 19454589 NLM ISO Abbreviation: Aging (Albany NY) Subsets: MEDLINE

مواضيع طبية MeSH: Aging/*metabolism , Aldehyde Dehydrogenase, Mitochondrial/*genetics , Apoptosis/*genetics , Endoplasmic Reticulum/*metabolism , Oxidative Stress/*genetics , Retina/*metabolism , Unfolded Protein Response/*genetics, Aging/pathology ; Aldehyde Dehydrogenase, Mitochondrial/drug effects ; Aldehyde Dehydrogenase, Mitochondrial/metabolism ; Animals ; Apoptosis/drug effects ; Benzamides/pharmacology ; Benzodioxoles/pharmacology ; Electroretinography ; Endoplasmic Reticulum/drug effects ; Endoplasmic Reticulum Chaperone BiP ; Fundus Oculi ; Interleukin-1/metabolism ; Interleukin-6/metabolism ; Mice ; Mice, Transgenic ; Oxidative Stress/drug effects ; Retina/drug effects ; Retina/pathology ; Retina/physiopathology ; Tomography, Optical Coherence ; Tumor Necrosis Factor-alpha/metabolism ; Unfolded Protein Response/drug effects

مستخلص: During the process of aging, the retina exhibits chronic oxidative stress (OS) damage. Our preliminary experiment showed that acetaldehyde dehydrogenase 2 (ALDH2) could alleviate retinal damage caused by OS. This study aimed to explore whether ALDH2 could inhibit mice retinal cell apoptosis and enhance the function of unfolded protein response in endoplasmic reticulum (UPR ^ER ) through reducing OS in aging process. Retinal function and structure in vivo and in vitro were examined in aged ALDH2+ overexpression mice and ALDH2 agonist Alda1-treated aged mice. Levels of ALDH2, endoplasmic reticulum stress (ERS), apoptosis and inflammatory cytokines were evaluated. Higher expression of ALDH2 was observed at the outer nuclear layer (ONL) and the inner nuclear layer (INL) in aged ALDH2+ overexpression and aged Alda1-treated mice. Moreover, aged ALDH2+ overexpression mice and aged Alda1-treated mice exhibited better retinal function and structure. Increased expression of glucose-regulated protein 78 (GRP78) and ERS-related protein phosphorylated eukaryotic initiation factor 2 (peIF2α) and decreased expression of apoptosis-related protein, including C/EBP homologous protein (CHOP), caspase12 and caspase9, and retinal inflammatory cytokines were detected in the retina of aged ALDH2+ overexpression mice and aged Alda1-treated mice. The expression of ALDH2 in the retina was decreased in aging process. ALDH2 could reduce retinal oxidative stress and apoptosis, strengthen UPR ^ER during the aging process to improve retinal function and structure.

المؤلفون: Dossumbekova A; Department of Medicine, MC5068, Section of Emergency Medicine, Emergency Resuscitation Ctr., The University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA., Berdyshev EV, Gorshkova I, Shao Z, Li C, Long P, Joshi A, Natarajan V, Vanden Hoek TL

المصدر: American journal of physiology. Heart and circulatory physiology [Am J Physiol Heart Circ Physiol] 2008 Dec; Vol. 295 (6), pp. H2417-26. Date of Electronic Publication: 2008 Oct 17.

نوع المنشور: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.

بيانات الدورية: Publisher: American Physiological Society Country of Publication: United States NLM ID: 100901228 Publication Model: Print-Electronic Cited Medium: Print ISSN: 0363-6135 (Print) Linking ISSN: 03636135 NLM ISO Abbreviation: Am J Physiol Heart Circ Physiol Subsets: MEDLINE

مواضيع طبية MeSH: Capillary Permeability/*drug effects , Coronary Vessels/*drug effects , Endothelium, Vascular/*drug effects , Hydrogen Peroxide/*pharmacology , Microvessels/*drug effects , Nitric Oxide Synthase Type III/*metabolism , Oxidants/*pharmacology , Oxidative Stress/*drug effects , Proto-Oncogene Proteins c-akt/*metabolism, Cells, Cultured ; Chromones/pharmacology ; Coronary Vessels/enzymology ; Dose-Response Relationship, Drug ; Endothelium, Vascular/enzymology ; Humans ; Microvessels/enzymology ; Morpholines/pharmacology ; NG-Nitroarginine Methyl Ester/pharmacology ; Nitric Oxide/metabolism ; Nitric Oxide Synthase Type III/antagonists & inhibitors ; Nucleosides/pharmacology ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphoinositide-3 Kinase Inhibitors ; Phosphorylation ; Protein Kinase Inhibitors/pharmacology ; Pyridazines/pharmacology ; Reactive Oxygen Species/metabolism ; Time Factors

مستخلص: The integrity of microvascular endothelium is an important regulator of myocardial contractility. Microvascular barrier integrity could be altered by increased reactive oxygen species (ROS) stress seen within minutes after cardiac arrest resuscitation. Akt and its downstream target nitric oxide (NO) synthase (NOS)3 can protect barrier integrity during ROS stress, but little work has studied these oxidant stress responses in human cardiac microvascular endothelial cells (HCMVEC). We, therefore, studied how ROS affects barrier function and NO generation via Akt and its downstream target NOS3 in HCMVEC. HCMVEC exposed to 500 microM H2O2 had increased Akt phosphorylation within 10 min at both Ser-473 and Thr-308 sites, an effect blocked by the phosphatidylinositol 3-kinase inhibitor LY-294002. H2O2 also induced NO generation that was associated with NOS3 Ser-1177 site phosphorylation and Thr-495 dephosphorylation, with Ser-1177 effects attenuated by LY-294002 and an Akt inhibitor, Akt/PKB signaling inhibitor-2 (API-2). H2O2 induced significant barrier disruption in HCMVEC within minutes, but recovery started within 30 min and normalized over hours. The NOS inhibitor Nomega-nitro-L-arginine methyl ester (200 microM) blocked NO generation but had no effect on H2O2-induced barrier permeability or the recovery of barrier integrity. By contrast, the Akt inhibitor API-2 abrogated HCMVEC barrier restoration. These results suggest that oxidant stress in HCMVEC activates NOS3 via Akt. NOS3/NO are not involved in the regulation of H2O2-affected barrier function in HCMVEC. Independent of NOS3 regulation, Akt proves to be critical for the restoration of barrier integrity in HCMVEC.

المؤلفون: Lu Wang, Canyang Zhang, Long Pang, Yan Wang

المصدر: BMC Complementary Medicine and Therapies, Vol 23, Iss 1, Pp 1-13 (2023)

مصطلحات موضوعية: Age-related maculopathy (AMD), Ferroptosis, Oxidative stress, Traditional Chinese medicine formula, Network pharmacology, Other systems of medicine, RZ201-999

الوصف: Abstract Background Qihuang Granule (QHG) is a traditional prescription that has exhibited potential in safeguarding against age-related maculopathy (AMD). Salvia miltiorrhiza (SM) and Fructus lycii (FL) are the main components of QHG. Ferroptosis, a newly discovered, iron-dependent, regulated cell death pathway, have been implicated in the pathogenesis of AMD. This study delves into the intricate mechanism by which SM/FL and QHG confer protection against AMD by modulating the ferroptosis pathway, employing a combination of network pharmacology and experimental validation. Methods Bioactive compounds and potential targets of SM and FL were gathered from databases such as TCMSP, GeneCard, OMIM, and FerrDb, along with AMD-related genes and key genes responsible for ferroptosis regulation. Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis and protein–protein interaction (PPI) network were performed to discover the potential mechanism. The construction of an interaction network involving AMD, ferroptosis, SM/FL potential target genes was facilitated by the STRING database and realized using Cytoscape software. Subsequent validation was accomplished through molecular docking and in vitro cell experiments. Results Noteworthy active compounds including quercetin, tanshinone IIA, luteolin, cryptotanshinone, and hub targets such as HIF-1α, EGFR, IL6, and VEGFA were identified. KEGG enrichment unveiled the HIF-1 signalling pathway as profoundly enriched, and IL6 and VEGF were involved. The molecular docking revealed the significant active compounds with hub genes and quercetin showed good binding to HIF-1α, which is involved in inflammation and angiogenesis. Experimental results verified that both herbs and QHG could regulate key ferroptosis-related targets in the retinal pigment epithelium and inhibit the expression of HIF-1α, VEGFA, and IL-6, subsequently increase cell viability and decrease the ROS content induced by H2O2. Conclusion This study demonstrates the molecular mechanism through which SM/FL and QHG protect against AMD and emerges as a plausible mechanism underlying this protection.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2662-7671

URL الوصول: https://doaj.org/article/cacbd1ed48ea44c38fe78a7beec1b30f

المؤلفون: Yan Wang, Huangxuan Shen, Long Pang, Bo Qiu, Yuan Yuan, Xiaoying Guan, Xiaolan Xiang

المصدر: BMC Complementary Medicine and Therapies, Vol 23, Iss 1, Pp 1-12 (2023)

مصطلحات موضوعية: Age-related macular degeneration, Alternative complement pathway, Oxidative stress, Traditional Chinese medicine, Qihuang Granule, Other systems of medicine, RZ201-999

الوصف: Abstract Background Age-related macular degeneration (AMD) is a leading cause of vision loss in elderly people, and dry AMD is the most common type of AMD. Oxidative stress and alternative complement pathway activation may play essential roles in the pathogenesis of dry AMD. There are no available drugs for dry AMD. Qihuang Granule (QHG) is an herbal formula for the treatment of dry AMD, and it achieves a good clinical effect in our hospital. However, its potential mechanism is unclear. Our study investigated the effects of QHG on oxidative stress-associated retinal damage to reveal its underlying mechanism. Methods Oxidative stress models were established using H2O2 and NaIO3 in ARPE-19 cells and C57BL/6 mice. Cell apoptosis and viability were assessed using phase contrast microscopy and flow cytometry, respectively. Alterations in the mouse retinal structure were evaluated using Masson staining and transmission electron microscopy (TEM). The expression of complement factor H (CFH), complement component 3a (C3a) and complement component 5a (C5a) in retinal pigment epithelium (RPE) cells and mice was measured using RT‒PCR, Western blot analysis and ELISA. Results Pretreatment with QHG significantly prevented cell apoptosis and disorder of the RPE and inner segment/outer segment (IS/OS) in H2O2-treated RPE cells and NaIO3-injected mice. QHG alleviated mitochondrial damage in mouse RPE cells, as shown by TEM. QHG also promoted CFH expression and inhibited the expression of C3a and C5a. Conclusions The results suggest that QHG protects the retinal pigment epithelium from oxidative stress, likely by regulating the alternative complement pathway.

وصف الملف: electronic resource

Relation: https://doaj.org/toc/2662-7671

URL الوصول: https://doaj.org/article/73fc7ab7b396493fa98fa3bc416127a0

المؤلفون: Shang, Nian-ying, Huang, Long-jian, Lan, Jia-qi, Kang, Yu-ying, Tang, Jing-shu, Wang, Hong-yue, Li, Xin-nan, Sun, Zhuo, Chen, Qiu-yu, Liu, Meng-yao, Wen, Zi-peng, Feng, Xin-hong, Wu, Lei, Peng, Ying^{Aff1, IDs41401024012409_cor14}

المصدر: Acta Pharmacologica Sinica. 45(6):1142-1159

المؤلفون: Mai, Nguyen, Wu, Long, Uruk, Gokhan, Mocanu, Ebony, Swanson, Raymond A

مصطلحات موضوعية: cofilactin rods, glutamate signaling, NADPH oxidase, neurite injury, oxidative stress, oxygen-glucose deprivation, Biochemistry and Cell Biology, Neurosciences, Neurology & Neurosurgery, Biochemistry and cell biology

الوصف: Cofilactin rods (CARs), which are 1:1 aggregates of cofilin-1 and actin, lead to neurite loss in ischemic stroke and other disorders. The biochemical pathways driving CAR formation are well-established, but how these pathways are engaged under ischemic conditions is less clear. Brain ischemia produces both ATP depletion and glutamate excitotoxicity, both of which have been shown to drive CAR formation in other settings. Here, we show that CARs are formed in cultured neurons exposed to ischemia-like conditions: oxygen-glucose deprivation (OGD), glutamate, or oxidative stress. Of these conditions, only OGD produced significant ATP depletion, showing that ATP depletion is not required for CAR formation. Moreover, the OGD-induced CAR formation was blocked by the glutamate receptor antagonists MK-801 and kynurenic acid; the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase inhibitors GSK2795039 and apocynin; as well as an ROS scavenger. The findings identify a biochemical pathway leading from OGD to CAR formation in which the glutamate release induced by energy failure leads to activation of neuronal glutamate receptors, which in turn activates NADPH oxidase to generate oxidative stress and CARs.

وصف الملف: application/pdf

URL الوصول: https://escholarship.org/uc/item/0nr4q24q

المؤلفون: Man, Jin, Zhang, Qian, Zhao, Tianhe, Sun, Donglei, Sun, Weilian, Long, Keyan, Zhang, Zunzhen^{Aff1, IDs12011023037287_cor7}

المصدر: Biological Trace Element Research. 202(3):885-899

المؤلفون: Sun, Huiying, Chen, Jia, Xiong, Dongwei, Long, Miao^{Aff1, IDs12011023035765_cor4}

المصدر: Biological Trace Element Research. 201(11):5441-5454

المؤلفون: Wei, Lanlan, Li, Bowen, Long, Jing, Fu, Yanping^{Aff4, IDs13205023038864_cor4}, Feng, Bin^{Aff5, IDs13205023038864_cor5}

المصدر: 3 Biotech. 14(3)