|
1
|
Nishant P, Gurnani B, Singh P, Sinha S, Kaur K, Kumar A, Sinha RK. Current concepts and recent trends in endothelial keratoplasty. World J Transplant 2025; 15. [DOI: 10.5500/wjt.v15.i2.102507] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2024] [Revised: 01/15/2025] [Accepted: 01/21/2025] [Indexed: 02/21/2025] Open
Abstract
Endothelial keratoplasty (EK) is defined as an umbrella term comprising methods for selective surgical replacement of corneal endothelium and adjacent corneal tissue, which retains healthy portions of a patient's cornea while replacing diseased innermost corneal layer(s) with healthy donor tissue, to achieve corneal dehydration and transparency before the onset of irreversible stromal edema and permanent loss of corneal clarity. Recently, the pathophysiology of corneal decompensation is increasingly being researched upon. Consequent improvement in pharmacotherapy is progressively leading to reduction in the indications of EK. In addition, EK techniques have progressed towards using thinner tissue, optimizing visual outcomes. Improvements have enabled better donor tissue formulation, usage, and attachment, and surgical modifications have enhanced the tissue utilization in difficult clinical scenarios lowering failure and rejection. However, challenges are encountered in various complex clinical scenarios including eyes with prior intraocular surgery, complex anterior chamber anatomy, glaucoma, ocular surface disease etc. These complexities demand tailored surgical strategies, including modifications in graft handling, instrumentation, and postoperative management to ensure success. Attention to these details and addressing patient-specific factors can help improve outcomes in these difficult cases. The choice of procedure depends on multiple factors, including the surgeon's experience, patient's ocular anatomy, and the specific clinical scenario. This review article encompasses the recent developments in this field presenting a comprehensive picture of our modern understanding of the indications, contraindications, surgical techniques, clinical situations, community aspects and future directions pertaining to EK.
Collapse
Affiliation(s)
- Prateek Nishant
- Department of Ophthalmology-Refractive Surgery, Uvea and Neuro-Ophthalmology, Akhand Jyoti Eye Hospital, Mastichak, Saran 841219, Bihar, India
| | - Bharat Gurnani
- Department of Cataract, Cornea, External Diseases, Trauma, Ocular Surface, Refractive Surgery and Contact Lens, Gomabai Netralaya and Research Center, Neemuch 458441, Madhya Pradesh, India
| | - Prabhakar Singh
- Department of Ophthalmology-Cornea and Ocular Surface, All India Institute of Medical Sciences, Kalyani 741245, West Bengal, India
| | - Sony Sinha
- Department of Ophthalmology-Vitreo-Retina, Neuro-Ophthalmology and Oculoplasty, All India Institute of Medical Sciences, Patna 801507, Bihar, India
| | - Kirandeep Kaur
- Department of Cataracts, Pediatric Ophthalmology and Strabismus, Gomabai Netralaya and Research Center, Neemuch 458441, Madhya Pradesh, India
| | - Ashish Kumar
- Department of Cornea and Refractive Surgery, Laxmi Netralaya, Jamal Road, Patna 800001, Bihar, India
| | - Ranjeet Kumar Sinha
- Department of Community Medicine, Patna Medical College, Patna 800004, Bihar, India
| |
Collapse
|
|
2
|
Tratnig-Frankl M, Luft N, Magistro G, Priglinger S, Ohlmann A, Kassumeh S. Hepatocyte Growth Factor Modulates Corneal Endothelial Wound Healing In Vitro. Int J Mol Sci 2024; 25:9382. [PMID: 39273330 PMCID: PMC11395100 DOI: 10.3390/ijms25179382] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2024] [Revised: 08/22/2024] [Accepted: 08/27/2024] [Indexed: 09/15/2024] Open
Abstract
In this study, we assessed the impact of hepatocyte growth factor (HGF) on corneal endothelial cells (CECs), finding that HGF concentrations of 100-250 ng/mL significantly increased CEC proliferation by 30%, migration by 32% and improved survival under oxidative stress by 28% compared to untreated controls (p < 0.05). The primary objective was to identify non-fibrotic pharmacological strategies to enhance corneal endothelial regeneration, addressing a critical need in conditions like Fuchs' endothelial dystrophy (FED), where donor tissue is scarce. To confirm the endothelial nature of the cultured CECs, Na+/K+-ATPase immunohistochemistry was performed. Proliferation rates were determined through BrdU incorporation assays, while cell migration was assessed via scratch assays. Cell viability was evaluated under normal and oxidative stress conditions using WST-1 assays. To ensure that HGF treatment did not trigger epithelial-mesenchymal transition, which could lead to undesirable fibrotic changes, α-SMA staining was conducted. These comprehensive methodologies provided robust data on the effects of HGF, confirming its potential as a therapeutic agent for corneal endothelial repair without inducing harmful EMT, as indicated by the absence of α-SMA expression. These findings suggest that HGF holds therapeutic promise for enhancing corneal endothelial repair, warranting further investigation in in vivo models to confirm its clinical applicability.
Collapse
Affiliation(s)
- Merle Tratnig-Frankl
- Department of Ophthalmology, LMU University Hospital, Ludwig-Maximilians University Munich, Mathildenstrasse 8, 80336 Munich, Germany
- Department of Ophthalmology and Optometry, Medical University Vienna, AKH Vienna, Währinger Gürtel 18-20, 1090 Vienna, Austria
| | - Nikolaus Luft
- Department of Ophthalmology, LMU University Hospital, Ludwig-Maximilians University Munich, Mathildenstrasse 8, 80336 Munich, Germany
| | - Guiseppe Magistro
- Department of Urology, Asklepios Westklinikum Hamburg GmbH, Suurheid 20, 22559 Hamburg, Germany
| | - Siegfried Priglinger
- Department of Ophthalmology, LMU University Hospital, Ludwig-Maximilians University Munich, Mathildenstrasse 8, 80336 Munich, Germany
| | - Andreas Ohlmann
- Department of Ophthalmology, LMU University Hospital, Ludwig-Maximilians University Munich, Mathildenstrasse 8, 80336 Munich, Germany
| | - Stefan Kassumeh
- Department of Ophthalmology, LMU University Hospital, Ludwig-Maximilians University Munich, Mathildenstrasse 8, 80336 Munich, Germany
| |
Collapse
|
|
3
|
Krok E, Stephan M, Dimova R, Piatkowski L. Tunable biomimetic bacterial membranes from binary and ternary lipid mixtures and their application in antimicrobial testing. BIOCHIMICA ET BIOPHYSICA ACTA. BIOMEMBRANES 2023; 1865:184194. [PMID: 37328023 DOI: 10.1016/j.bbamem.2023.184194] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/13/2023] [Revised: 06/05/2023] [Accepted: 06/08/2023] [Indexed: 06/18/2023]
Abstract
The reconstruction of accurate yet simplified mimetic models of cell membranes is a very challenging goal of synthetic biology. To date, most of the research focuses on the development of eukaryotic cell membranes, while reconstitution of their prokaryotic counterparts has not been fully addressed, and the proposed models do not reflect well the complexity of bacterial cell envelopes. Here, we describe the reconstitution of biomimetic bacterial membranes with an increasing level of complexity, developed from binary and ternary lipid mixtures. Giant unilamellar vesicles composed of phosphatidylcholine (PC) and phosphatidylethanolamine (PE); PC and phosphatidylglycerol (PG); PE and PG; PE, PG and cardiolipin (CA) at varying molar ratios were successfully prepared by the electroformation method. Each of the proposed mimetic models focuses on reproducing specific membrane features such as membrane charge, curvature, leaflets asymmetry, or the presence of phase separation. GUVs were characterized in terms of size distribution, surface charge, and lateral organization. Finally, the developed models were tested against the lipopeptide antibiotic daptomycin. The obtained results showed a clear dependency of daptomycin binding efficiency on the amount of negatively charged lipid species present in the membrane. We anticipate that the models proposed here can be applied not only in antimicrobial testing but also serve as platforms for studying fundamental biological processes in bacteria as well as their interaction with physiologically relevant biomolecules.
Collapse
Affiliation(s)
- Emilia Krok
- Poznan University of Technology, Faculty of Materials Engineering and Technical Physics, Institute of Physics, Piotrowo 3, 60-965 Poznan, Poland; Max Planck Institute of Colloids and Interfaces, Science Park Golm, 14476 Potsdam, Germany.
| | - Mareike Stephan
- Max Planck Institute of Colloids and Interfaces, Science Park Golm, 14476 Potsdam, Germany
| | - Rumiana Dimova
- Max Planck Institute of Colloids and Interfaces, Science Park Golm, 14476 Potsdam, Germany.
| | - Lukasz Piatkowski
- Poznan University of Technology, Faculty of Materials Engineering and Technical Physics, Institute of Physics, Piotrowo 3, 60-965 Poznan, Poland
| |
Collapse
|
|
4
|
Sauve S, Williamson J, Polasa A, Moradi M. Ins and Outs of Rocker Switch Mechanism in Major Facilitator Superfamily of Transporters. MEMBRANES 2023; 13:membranes13050462. [PMID: 37233523 DOI: 10.3390/membranes13050462] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/31/2023] [Revised: 04/20/2023] [Accepted: 04/23/2023] [Indexed: 05/27/2023]
Abstract
The major facilitator superfamily (MFS) of transporters consists of three classes of membrane transporters: symporters, uniporters, and antiporters. Despite such diverse functions, MFS transporters are believed to undergo similar conformational changes within their distinct transport cycles, known as the rocker-switch mechanism. While the similarities between conformational changes are noteworthy, the differences are also important since they could potentially explain the distinct functions of symporters, uniporters, and antiporters of the MFS superfamily. We reviewed a variety of experimental and computational structural data on a select number of antiporters, symporters, and uniporters from the MFS family to compare the similarities and differences of the conformational dynamics of three different classes of transporters.
Collapse
Affiliation(s)
- Stephanie Sauve
- Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USA
| | - Joseph Williamson
- Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USA
| | - Adithya Polasa
- Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USA
| | - Mahmoud Moradi
- Department of Chemistry and Biochemistry, University of Arkansas, Fayetteville, AR 72701, USA
| |
Collapse
|
|
5
|
Rahimi Z, Lohrasebi A. Impacts of external electric fields on the permeation of glycerol and water molecules through aquaglyceroporin-7: molecular dynamics simulation approach. THE EUROPEAN PHYSICAL JOURNAL. E, SOFT MATTER 2023; 46:3. [PMID: 36656387 DOI: 10.1140/epje/s10189-023-00261-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/23/2022] [Accepted: 01/09/2023] [Indexed: 06/17/2023]
Abstract
The aquaglyceroporin-7 (AQP7) protein channels facilitate the permeation of glycerol and water molecules through cell membranes by passive diffusion and play a crucial role in cell physiology. Considering the wide-spirit usage of radiofrequency electromagnetic fields in our daily life, in this study, the effects of constant and GHz electric fields were investigated on the dynamics of glycerol and water molecules inside the AQP7. To this end, four different molecular simulation groups were carried out in the absence and presence of electric fields. The results reveal that the free energy profile of the glycerol permeation inside the channel is reduced in the presence of the field of 0.2 mV/nm and the oscillating field of 10 GHz. In addition, exposing the channel to the electric field of 0.2 mV/nm assisted the water transport through the channel with no considerable effect on channel stability. These observations provide a framework for understanding how such fields could alter normal operation of protein channels, which may lead to disease beginning or being used in disease treatment. Glycerol and water molecules permeation through the aquaglyceroporin-7 channel can be influenced by application of external electric fields.
Collapse
Affiliation(s)
- Zeinab Rahimi
- Department of Physics, University of Isfahan, P.O. Box 81746-73441, Isfahan, Iran
| | - Amir Lohrasebi
- Department of Physics, University of Isfahan, P.O. Box 81746-73441, Isfahan, Iran.
| |
Collapse
|
|
6
|
Pathogenesis and treatment principles ocular damage by self-defense gas weapons. OPHTHALMOLOGY JOURNAL 2022. [DOI: 10.17816/ov105683] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022] Open
Abstract
The article presents the pathogenetic mechanisms of eye damage by gas self-defense weapons in detail. We discuss the mechanisms of eye damage and structural changes of the tissues after gas-trauma. The causes of these changes and the main clinical manifestations accompanying them are analyzed. We analyzed the factors, influencing the development of dystrophic changes of the ocular surface in detail. The information on various techniques for self-assistance, mutual aid and earlier specific treatment of this injury was summarized. An aqueous solution of pediphene substance promising for use is considered, which has a number of pharmacological properties that fundamentally affect the pathogenetic mechanisms of gas-weapon trauma. Its effectiveness was shown in the experiment in comparison with the control group without treatment and the group using the combined drug-dexamethasone in combination with an antibiotic.
Collapse
|
|
7
|
Abstract
The internal energy (U-energy) conversion to free energy (F-energy) and energy dissipation (S-energy) is a basic process that enables the continuity of life on Earth. Here, we present a novel method of evaluating F-energy in a membrane system containing ternary solutions of non-electrolytes based on the Kr version of the Kedem–Katchalsky–Peusner (K–K–P) formalism for concentration polarization conditions. The use of this formalism allows the determination of F-energy based on the production of S-energy and coefficient of the energy conversion efficiency. The K–K–P formalism requires the calculation of the Peusner coefficients Kijr and Kdetr (i, j ∈ {1, 2, 3}, r = A, B), which are necessary to calculate S-energy, the degree of coupling and coefficients of energy conversion efficiency. In turn, the equations for S-energy and coefficients of energy conversion efficiency are used in the F-energy calculations. The Kr form of the Kedem–Katchalsky–Peusner model equations, containing the Peusner coefficients Kijr and Kdetr, enables the analysis of energy conversion in membrane systems and is a useful tool for studying the transport properties of membranes. We showed that osmotic pressure dependences of indicated Peusner coefficients, energy conversion efficiency coefficient, entropy and energy production are nonlinear. These nonlinearities were caused by pseudophase transitions from non-convective to convective states or vice versa. The method presented in the paper can be used to assess F-energy resources. The results can be adapted to various membrane systems used in chemical engineering, environmental engineering or medical applications. It can be used in designing new technologies as a part of process management.
Collapse
|
|
8
|
Affiliation(s)
- Chandra Has
- Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai, India
| |
Collapse
|
|
9
|
Batko KM, Ślęzak A. Evaluation of the Global S-Entropy Production in Membrane Transport of Aqueous Solutions of Hydrochloric Acid and Ammonia. ENTROPY (BASEL, SWITZERLAND) 2020; 22:E1021. [PMID: 33286790 PMCID: PMC7597114 DOI: 10.3390/e22091021] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 08/12/2020] [Revised: 09/04/2020] [Accepted: 09/10/2020] [Indexed: 11/29/2022]
Abstract
The results of experimental studies of volume osmotic fluxes (Jvkr) and fluxes of dissolved substances (Jkr) in a system containing a synthetic Nephrophan® membrane (Orwo VEB Filmfabrik, Wolfen, Germany) set in a horizontal plane are presented. The membrane separated water and aqueous HCl or ammonia solutions or aqueous ammonia and HCl solutions. It was found that for the homogeneity conditions of the solutions Jvk and Jk depend only on the concentration and composition of the solutions. For concentration polarization conditions (where concentration boundary layers are created on both sides), Jvkr and Jkr depend on both the concentration and composition of the solutions and the configuration of the membrane system. The obtained results of the Jvk and Jk flux studies were used to assess the global production of entropy for the conditions of homogeneity of solutions (ΦSk), while Jvkr and Jkr-to assess the global production of entropy for concentration polarization conditions (ΦSkr). In addition, the diffusion-convective effects and the convection effect in the global source of entropy were calculated. The concentration polarization coefficient ζir was related to modified concentration Rayleigh number, e.g., the parameter controlling the transition from non-convective (diffusive) to convective state. This number acts as a switch between two states of the concentration field: convective (with a higher entropy source value) and non-convective (with a lower entropy source value). The operation of this switch indicates the regulatory role of earthly gravity in relation to membrane transport.
Collapse
Affiliation(s)
- Kornelia M. Batko
- Department of Business Informatics, University of Economics, 40287 Katowice, Poland
| | - Andrzej Ślęzak
- Department of Health Science, Jan Dlugosz University, 13/15 Armia Krajowa Al., 42200 Częstochowa, Poland;
| |
Collapse
|
|
10
|
Batko KM, Ślęzak A, Grzegorczyn S, Bajdur WM. The Rr Form of the Kedem-Katchalsky-Peusner Model Equations for Description of the Membrane Transport in Concentration Polarization Conditions. ENTROPY (BASEL, SWITZERLAND) 2020; 22:E857. [PMID: 33286628 PMCID: PMC7517459 DOI: 10.3390/e22080857] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 07/29/2020] [Accepted: 07/30/2020] [Indexed: 11/25/2022]
Abstract
The paper presents the Rr matrix form of Kedem-Katchalsky-Peusner equations for membrane transport of the non-homogeneous ternary non-electrolyte solutions. Peusner's coefficients Rijr and det [Rr] (i, j ∈ {1, 2, 3}, r = A, B) occurring in these equations, were calculated for Nephrophan biomembrane, glucose in aqueous ethanol solutions and two different settings of the solutions relative to the horizontally oriented membrane for concentration polarization conditions or homogeneity of solutions. Kedem-Katchalsky coefficients, measured for homogeneous and non-homogeneous solutions, were used for the calculations. The calculated Peusner's coefficients for homogeneous solutions depend linearly, and for non-homogeneous solutions non-linearly on the concentrations of solutes. The concentration dependences of the coefficients Rijr and det [Rr] indicate a characteristic glucose concentration of 9.24 mol/m3 (at a fixed ethanol concentration) in which the obtained curves for Configurations A and B intersect. At this point, the density of solutions in the upper and lower membrane chamber are the same. Peusner's coefficients were used to assess the effect of concentration polarization and free convection on membrane transport (the ξij coefficient), determine the degree of coupling (the rijr coefficient) and coupling parameter (the QRr coefficient) and energy conversion efficiency (the (eijr)r coefficient).
Collapse
Affiliation(s)
- Kornelia M. Batko
- Department of Business Informatics, University of Economics, 40287 Katowice, Poland
| | - Andrzej Ślęzak
- Department of Innovation and Safety Management Systems, Technical University of Czestochowa, 42200 Czestochowa, Poland;
| | - Sławomir Grzegorczyn
- Department of Biophysics, Faculty of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, 19 H. Jordan Str., 41808 Zabrze, Poland;
| | - Wioletta M. Bajdur
- Department of Innovation and Safety Management Systems, Technical University of Czestochowa, 42200 Czestochowa, Poland;
| |
Collapse
|
|
11
|
Ślęzak A, Bajdur WM, Batko KM, Šcurek R. Simulation of S-Entropy Production during the Transport of Non-Electrolyte Solutions in the Double-Membrane System. ENTROPY 2020; 22:e22040463. [PMID: 33286237 PMCID: PMC7516942 DOI: 10.3390/e22040463] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/23/2020] [Revised: 04/13/2020] [Accepted: 04/17/2020] [Indexed: 12/02/2022]
Abstract
Using the classical Kedem–Katchalsky’ membrane transport theory, a mathematical model was developed and the original concentration volume flux (Jv), solute flux (Js) characteristics, and S-entropy production by Jv, ((ψS)Jv) and by Js((ψS)Js) in a double-membrane system were simulated. In this system, M1 and Mr membranes separated the l, m, and r compartments containing homogeneous solutions of one non-electrolytic substance. The compartment m consists of the infinitesimal layer of solution and its volume fulfills the condition Vm → 0. The volume of compartments l and r fulfills the condition Vl = Vr → ∞. At the initial moment, the concentrations of the solution in the cell satisfy the condition Cl < Cm < Cr. Based on this model, for fixed values of transport parameters of membranes (i.e., the reflection (σl, σr), hydraulic permeability (Lpl, Lpr), and solute permeability (ωl, ωr) coefficients), the original dependencies Cm = f(Cl − Cr), Jv = f(Cl − Cr), Js = f(Cl − Cr), (ΨS)Jv = f(Cl − Cr), (ΨS)Js = f(Cl − Cr), Rv = f(Cl − Cr), and Rs = f(Cl − Cr) were calculated. Each of the obtained features was specially arranged as a pair of parabola, hyperbola, or other complex curves.
Collapse
Affiliation(s)
- Andrzej Ślęzak
- Department of Innovation and Safety Management Systems, Technical University of Czestochowa, 42200 Czestochowa, Poland;
| | - Wioletta M. Bajdur
- Department of Innovation and Safety Management Systems, Technical University of Czestochowa, 42200 Czestochowa, Poland;
- Correspondence: (W.M.B.); (K.M.B.)
| | - Kornelia M. Batko
- Department of Business Informatics, University of Economics, 40287 Katowice, Poland
- Correspondence: (W.M.B.); (K.M.B.)
| | - Radomir Šcurek
- Department of Security Services, Faculty of Safety Engineering, VSB-Ostrava, 70030 Ostrava, Czech Republic;
| |
Collapse
|
|
12
|
Abstract
Background Biomechanics introduces numerous technologies to support clinical practice in ophthalmology, with the goal of improving surgical outcomes and to develop new advanced technologies with minimum impact on clinical training. Unfortunately, a few misconceptions on the way that computational methods should be applied to living tissues contributes to a lack of confidence towards computer-based approaches. Methods Corneal biomechanics relies on sound theories of mechanics, including concepts of equilibrium, geometrical measurements, and complex material behaviors. The peculiarities of biological tissues require the consideration of multi-physics, typical of the eye environment, and to adopt customized geometrical models constructed on the basis of advanced optical imaging and in-vivo testing. Results Patient-specific models are able to predict the outcomes of refractive surgery and to exploit the results of in-vivo test to characterize the material properties of the corneal tissue. Conclusions Corneal biomechanics can become an important support to clinical practice, provided that methods are based on the actual multi-physics and use customized geometrical and mechanical models.
Collapse
Affiliation(s)
- Anna Pandolfi
- Department of Civil and Environmental Engineering, Politecnico di Milano, Piazza Leonardo da Vinci 32, Milano, 20133 Italy
| |
Collapse
|
|
13
|
De Schepper W, Moraru M, Jacobs B, Oudshoorn M, Helsen J. Electrodialysis of aqueous NaCl-glycerol solutions: A phenomenological comparison of various ion exchange membranes. Sep Purif Technol 2019. [DOI: 10.1016/j.seppur.2019.02.030] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
|
|
14
|
Zhang J, Han Y, Zhao Y, Li Q, Jin H, Qin J. Inhibition of TRIB3 Protects Against Neurotoxic Injury Induced by Kainic Acid in Rats. Front Pharmacol 2019; 10:585. [PMID: 31191318 PMCID: PMC6538922 DOI: 10.3389/fphar.2019.00585] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2019] [Accepted: 05/06/2019] [Indexed: 11/13/2022] Open
Abstract
Epilepsy refers to a group of neurological disorders of varying etiologies characterized by recurrent seizures, resulting in brain dysfunction. Endoplasmic reticulum (ER) stress is highly activated in the process of epilepsy-related brain injury. However, the mechanisms by which ER stress triggers neuronal apoptosis remain to be fully elucidated. Tribbles pseudokinase 3 (TRIB3) is a pseudokinase that affects a number of cellular functions, and its expression is increased during ER stress. Here, we sought to clarify the role of TRIB3 in neuronal apoptosis mediated by ER stress. In the kainic acid (KA) (10 mg/kg)-induced rat seizure model, we characterized neuronal injury and apoptosis after KA injection. KA induced an ER stress response, as indicated by elevated expression of glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP). TRIB3 protein was upregulated concomitantly with the downregulation of phosphorylated-protein kinase B (p-AKT) in rats following KA administration. In rat cortical neurons treated with KA, TRIB3 knockdown by siRNA reduced the number of dying neurons, decreased the induction of GRP78 and CHOP and the activation of caspase-3, and blocked the dephosphorylation of AKT after KA treatment. Our findings indicate that TRIB3 is involved in neuronal apoptosis occurring after KA-induced seizure. The knockdown of TRIB3 effectively protects against neuronal apoptosis in vitro, suggesting that TRIB3 may be a potential therapeutic target for the treatment of epilepsy.
Collapse
Affiliation(s)
- Jing Zhang
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Ying Han
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Yang Zhao
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Qinrui Li
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Hongfang Jin
- Department of Pediatrics, Peking University First Hospital, Beijing, China
| | - Jiong Qin
- Department of Pediatrics, Peking University People's Hospital, Beijing, China
| |
Collapse
|
|
15
|
Membrane Transport of Nonelectrolyte Solutions in Concentration Polarization Conditions: Hr Form of the Kedem–Katchalsky–Peusner Equations. INTERNATIONAL JOURNAL OF CHEMICAL ENGINEERING 2019. [DOI: 10.1155/2019/5629259] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
Abstract
In this paper, the Kedem–Katchalsky equations in matrix form for nonhomogeneous ternary nonelectrolyte solutions were applied for interpretation of transport through the membrane mounted in horizontal plane. Coefficients Hijr, Hijr, and Hdetr=detHr (for nonhomogeneous solutions), Hij and Hdet=detH (for homogeneous solutions) (i, j ∈ {1, 2, 3}, r = A, B), ψij=HijA−HijB/Hij, and ψdet=HdetA−HdetB/Hdet were calculated on the basis of experimentally determined coefficients (Lp, σ1, σ2ω11, ω22, ω21, ω12, ζ1r, and ζ2r) for glucose in aqueous ethanol solutions and two configurations of the membrane system. From the calculations, it results that the values of coefficients H12r, H13r, H22r, H23r, H32r, H33r, and Hdetr depend nonlinearly on solution concentration as well as on a configuration of membrane system. Besides, the values of coefficients H21r, H12, H21, H22, H33r, and Hdet depend linearly on solution concentration. The value of coefficients H13, H23, and H33 do not depend on solution concentration. The coefficients ψ12, ψ13, ψ22 = ψ23, ψ32 = ψ33, and ψdet depend nonlinearly on solution concentration and for C¯1 ≈ 9.24 mol m−3 are equal to zero. For C¯1 < 9.24 mol m−3, the values of coefficients ψ12 and ψ13 are negative and for C¯1 > 9.23 mol m−3, positive. In contrast, the values of coefficients ψ22 = ψ23, ψ32 = ψ33, and ψdet for C¯1 < 9.24 mol m−3 are positive and for C¯1 > 9.24 mol m−3, negative. For ψ = 0, we can observe nonconvective state, in which concentration Rayleigh number reaches the critical value RC = 1691.09, for ψ<0 is convective state with convection directed straight down and for ψ>0 is convective state with convection directed straight up.
Collapse
|
|
16
|
Zhang J, Wang Y, Zheng Z, Sun X, Chen T, Li C, Zhang X, Guo J. Intracellular ion and protein nanoparticle-induced osmotic pressure modify astrocyte swelling and brain edema in response to glutamate stimuli. Redox Biol 2019; 21:101112. [PMID: 30685709 PMCID: PMC6351271 DOI: 10.1016/j.redox.2019.101112] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 01/02/2019] [Accepted: 01/14/2019] [Indexed: 12/28/2022] Open
Abstract
Intracellular tension activity plays a crucial role in cytotoxic brain edema and astrocyte swelling. Here, a few genetically encoded FRET-based tension probes were designed to detect cytoskeletal structural tension optically, including their magnitude and vectors. The astrocyte swelling resulted in GFAP tension increment, which is associated with the antagonistic effect of inward microfilaments (MFs) and microtubules (MTs) forces. In glutamate-induced astrocyte swelling, GFAP tension rise resulted from outward ion and protein nanoparticle-induced osmotic pressure (PN-OP) increases, where PN-OP could be elicited by MF and MT depolymerization, protein nanoparticle production, and activation of cofilin and stathmin-1. Attenuation of both ion osmotic pressure and PN-OP by drug combinations, together with free-radical scavenger, relieved cerebral edema in vivo. The study suggests that intracellular osmotic pressure (especially PN-OP) has a pivotal role in glutamate-induced astrocyte swelling and brain edema. Recovery of cytoplasmic potential is a promising target to develop new drugs and cure brain edema.
Collapse
Affiliation(s)
- JiaRui Zhang
- State Key Laboratory Cultivation Base For TCM Quality and Efficacy, School of Medicine and Life Science, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; Key Laboratory of Drug Target and Drug for Degenerative Disease, Nanjing University of Chinese Medicine, Nanjing, PR China
| | - YuXuan Wang
- State Key Laboratory Cultivation Base For TCM Quality and Efficacy, School of Medicine and Life Science, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; Key Laboratory of Drug Target and Drug for Degenerative Disease, Nanjing University of Chinese Medicine, Nanjing, PR China
| | - ZiHui Zheng
- State Key Laboratory Cultivation Base For TCM Quality and Efficacy, School of Medicine and Life Science, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; Key Laboratory of Drug Target and Drug for Degenerative Disease, Nanjing University of Chinese Medicine, Nanjing, PR China
| | - XiaoHe Sun
- State Key Laboratory Cultivation Base For TCM Quality and Efficacy, School of Medicine and Life Science, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; Key Laboratory of Drug Target and Drug for Degenerative Disease, Nanjing University of Chinese Medicine, Nanjing, PR China
| | - TingTing Chen
- State Key Laboratory Cultivation Base For TCM Quality and Efficacy, School of Medicine and Life Science, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; Key Laboratory of Drug Target and Drug for Degenerative Disease, Nanjing University of Chinese Medicine, Nanjing, PR China
| | - Chen Li
- State Key Laboratory Cultivation Base For TCM Quality and Efficacy, School of Medicine and Life Science, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; Key Laboratory of Drug Target and Drug for Degenerative Disease, Nanjing University of Chinese Medicine, Nanjing, PR China
| | - XiaoLong Zhang
- State Key Laboratory Cultivation Base For TCM Quality and Efficacy, School of Medicine and Life Science, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; Key Laboratory of Drug Target and Drug for Degenerative Disease, Nanjing University of Chinese Medicine, Nanjing, PR China
| | - Jun Guo
- State Key Laboratory Cultivation Base For TCM Quality and Efficacy, School of Medicine and Life Science, Nanjing University of Chinese Medicine, Nanjing 210023, PR China; Key Laboratory of Drug Target and Drug for Degenerative Disease, Nanjing University of Chinese Medicine, Nanjing, PR China; Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing, PR China.
| |
Collapse
|