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Reviving the use of inhibitors of matrix metalloproteases in spinal cord injury:a case for specificity

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Neural Regeneration Research 2023年第9期18卷 1925-1930页

作者： zubair ahmed Neuroscience and Ophthalmology Institute of Inflammation and AgeingUniversity of BirminghamEdgbastonBirminghamUK Center for Trauma Sciences Research University of BimringhamEdgbastonBirminghamUK

At present,there are no resto rative therapies in the clinic for spinal cord injury,with current treatments offering only palliative treatment options.The role of matrix metalloproteases is well established in spinal cord injury,howeve r,translation into the clinical space was plagued by early designs of matrix metalloprotease inhibitors that lacked specificity and fears of musculos keletal syndrome prevented their further development.Newe r,much more specific matrix metalloprotease inhibitors have revived the possibility of using these inhibitors in the clinic since they are much more specific to their to rget matrix metalloproteases.Here,the evidence for use of matrix metalloproteases after spinal cord injury is reviewed and researche rs are urged to overcome their old fears rega rding matrix metalloprotease inhibition and possible side effects for the field to progress.Recently published work by us shows that inhibition of specific matrix metalloproteases after spinal cord injury holds promise since four key consequences of spinal cord injury could be alleviated by specific,next-gene ration matrix metalloprotease inhibitors.For example,specific inhibition of matrix metalloprotease-9 and matrix metalloprotease-12 within 24 hours after injury and for 3 days,alleviates spinal cord injury-induced edema,blood-s pinal co rd barrier breakdown,neuro pathic pain and resto res sensory and locomotor function.Attempts are now underway to translate this therapy into the clinic.

关键词： axon regeneration blood-spinal cord barrier edema functional recovery matrix metalloprotease-9 matrix metalloproteses-12 pain spinal cord injury

TBBPA rather than its main derivatives enhanced growth of endometrial cancer via p53 ubiquitination

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Journal of Environmental Sciences 2024年第3期137卷 82-95页

作者： Hongyan Yu Jingxu Zhang Jing Liu Ruonan Pan Yu Wang Xiaoting Jin Rifat zubair ahmed Yuxin Zheng Department of Occupational Health and Environmental Health School of Public HealthQingdao UniversityQingdao 266071China State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China Department of Genetics University of KarachiKarachi 75270Pakistan

Tetrabromobisphenol A(TBBPA)and its derivatives widely exist in various environments and biota.Although the available data indicate that TBBPA exposure is highly associated with the increased incidence of endometrial cancer(EC),the effects of TBBPA and its main derivatives on EC proliferation and the involved crucial mechanism remain unclear.The present study aimed to investigate the effects of TBBPA and its derivatives under environmental concentrations on the proliferation of EC,and the crucial mechanism on the progression of EC caused by bromine fame retardants exposure.In this research,TBBPA and two of the most common TBBPA derivatives including TBBPA bis(2-hydroxyethyl ether)(TBBPABHEE)and TBBPA bis(dibromopropyl ether)(TBBPA-BDBPE)were screened for their capacities in induced EC proliferation and explored the related mechanism by in vitro cell culture model and in vivo mice model.Under environmental concentrations,TBBPA promoted the proliferation of EC,the main derivatives of TBBPA(TBBPA-BHEE and TBBPA-BDBPE)did not present the similar facilitation effects.The ubiquitination degradation of p53 was crucial in TBBPA induced EC proliferation,which resulted in the increase of downstream cell cycle and decrease of apoptosis.The further molecular docking result suggested the high affinity between TBBPA and ubiquitinated proteasome.This finding revealed the effects of TBBPA and its derivatives on EC proliferation,thus providing novel insights into the underlying mechanisms of TBBPA-caused EC.

关键词： Tetrabromobisphenol A(TBBPA) Endometrial cancer(EC) Derivatives Ubiquitin proteases p53

Facies Analysis, Sequence Stratigraphy and Diagenetic Studies of the Jurassic Carbonates of the Kohat Basin, Northwest Pakistan: Reservoir Implications

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Acta Geologica Sinica(English Edition) 2022年第5期96卷 1673-1692页

作者： Emadullah KHAN Abbas Ali NASEEM Suleman KHAN Bilal WADOOD Faisal REHMAN Maryam SALEEM Mubashir MEHMOOD Waqar AHMAD zubair ahmed Tahir AZEEM Department of Earth Sciences Quaid-e-Azam UniversityIslamabad 45320Pakistan Department of Geology Abdul Wali Khan UniversityMardan 23200Pakistan Department of Geology University of PeshawarPeshawar 24420Pakistan State Key Laboratory of Continental Dynamics Department of GeologyNorthwest UniversityXi’an 71006China Department of Geology University of SwabiSwabi 23561Pakistan Department of Earth&Environmental Sciences Bahria UniversityIslamabad 44000Pakistan Department of Earth&Atmospheric Sciences University of AlbertaEdmonton T6G 2R3Canada

The present study deals with the depositional facies, diagenetic processes and sequence stratigraphy of the shallow marine carbonates of the Samana Suk Formation, Kohat Basin, in order to elucidate its reservoir quality. The Samana Suk Formation consists of thin to thick-bedded, oolitic, bioclastic, dolomitic and fractured limestone. Based on the integration of outcrop, petrographic and biofacies analyses, the unit is thought to have been deposited on a gentle homoclinal ramp in peritidal, lagoonal and carbonate shoal settings. Frequent variations in microfacies based sea-level curve have revealed seven Transgressive Systems Tracts(TSTs) and six Regressive Systems Tracts(RSTs). The unit has undergone various stages of diagenetic processes, including mechanical and chemical compaction, cementation,micritization, dissolution and dolomitization. The petrographic analyses show the evolution of porosity in various depositional and diagenetic phases. The fenestral porosity was mainly developed in peritidal carbonates during deposition,while the burial dissolution and diagenetic dolomitization have greatly enhanced the reservoir potential of the rock unit, as is further confirmed by the plug porosity and permeability analyses. The porosities and permeabilities were higher in shoal facies deposited in TSTs, as compared to lagoonal and peritidal facies, except for the dolomite in mudstone, deposited during RSTs. Hence good, moderate and poor reservoir potential is suggested for shoal, lagoonal and peritidal facies,respectively.

关键词： porosity diagenesis reservoir Samana Suk Formation Kohat Basin

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M-矩阵平方根的一类迭代法

应用数学 2022年第2期35卷 386-393页

作者：关晋瑞邵荣侠 zubair ahmed 太原师范学院数学系山西晋中030619 新疆财经大学统计与数据科学学院新疆乌鲁木齐830012 信德大学数学与计算机系信德贾姆肖罗71000

矩阵平方根在数学的许多应用中起着重要的作用.本文研究M-矩阵平方根的计算问题,提出一种计算正则M-矩阵平方根的迭代方法.首先将这个问题转化为M-矩阵代数Riccati方程,进而提出一种有效的方法来求解这个特殊的MARE.理论分析表明,该方... 详细信息

矩阵平方根在数学的许多应用中起着重要的作用.本文研究M-矩阵平方根的计算问题,提出一种计算正则M-矩阵平方根的迭代方法.首先将这个问题转化为M-矩阵代数Riccati方程,进而提出一种有效的方法来求解这个特殊的MARE.理论分析表明,该方法在一定条件下是收敛的.数值实验表明该方法是可行的,且优于二项式迭代法.

关键词：矩阵平方根正则M-矩阵代数Riccati方程二项式迭代

Decorin treatment of spinal cord injury

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Neural Regeneration Research 2014年第18期9卷 1653-1656页

作者： Maryam Esmaeili Martin Berry Ann Logan zubair ahmed Neurotrauma Research Group Neurobiology SectionSchool of Clinical and Experimental MedicineUniversity of Birmingham

The scarring response after a penetrant central nervous system injury results from the interaction between invading leptominingeal/pericyte-derived fibroblasts and endogenous reactive astrocytes about the wound margin. Extracellular matrix and scar-derived axon growth inhibitory mole- cules fill the lesion site providing both a physical and chemical barrier to regenerating axons. Dec orin, a small leucine-rich chondroitin-dermatan sulphate proteoglycan expressed by neurons and astrocytes in the central nervous system, is both anti-fibrotic and anti-inflammatory and attenu- ates the formation and partial dissolution of established and chronic scars. Here, we discuss the potential of using Decorin to antagonise scarring in the central nervous system.

关键词： spinal cord injury Decorin transforming growth factor-beta scarring chondroiti^sulphate proteoglycan matrix metalloproteases

Decorin treatment for reversing trabecular meshwork fibrosis in open-angle glaucoma

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Neural Regeneration Research 2016年第6期11卷 922-923页

作者： Lisa J Hill zubair ahmed Ann Logan Neuroscience and Ophthalmology University of Birmingham

In this perspective,we discuss the use of an anti-fibrotic agent Decorin to treat established fibrosis associated with glaucoma originally published by Hill et al.（2015）.Glaucoma describes a group of progressive opt... 详细信息

关键词： glaucoma trabecular originally irreversible progressive optic outflow ganglion progression elevated

LINGO-1 and AMIGO3, potential therapeutic targets for neurological and dysmyelinating disorders？

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Neural Regeneration Research 2017年第8期12卷 1247-1251页

作者： Simon Foale Martin Berry Ann Logan Daniel Fulton zubair ahmed Neuroscience and Ophthalmology Institute of Inflammation and Ageing University of Birmingham Birmingham UK

Leucine rich repeat proteins have gained considerable interest as therapeutic targets due to their expression and biological activity within the central nervous system. LINGO-1 has received particular attention since it inhibits axonal regeneration after spinal cord injury in a Rho A dependent manner while inhibiting leucine rich repeat and immunoglobulin-like domain-containing protein 1（LINGO-1） disinhibits neuron outgrowth. Furthermore, LINGO-1 suppresses oligodendrocyte precursor cell maturation and myelin production. Inhibiting the action of LINGO-1 encourages remyelination both in vitro and in vivo. Accordingly, LINGO-1 antagonists show promise as therapies for demyelinating diseases. An analogous protein to LINGO-1, amphoterin-induced gene and open reading frame-3（AMIGO3）, exerts the same inhibitory effect on the axonal outgrowth of central nervous system neurons, as well as interacting with the same receptors as LINGO-1. However, AMIGO3 is upregulated more rapidly after spinal cord injury than LINGO-1. We speculate that AMIGO3 has a similar inhibitory effect on oligodendrocyte precursor cell maturation and myelin production as with axogenesis. Therefore, inhibiting AMIGO3 will likely encourage central nervous system axonal regeneration as well as the production of myelin from local oligodendrocyte precursor cell, thus providing a promising therapeutic target and an area for future investigation.

关键词： multiple sclerosis demyelination oligodendrocyte AMIGO3 LINGO1 oligodendrocyte precursor cell

Cannabinoids: Do they have the potential to treat the symptoms of multiple sclerosis?

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World Journal of Neurology 2013年第4期3卷 87-96页

作者： zubair ahmed Neurotrauma and Neurodegeneration Section School of Clinical and Experimental MedicineCollege of Medical and Dental Sciences University of Birmingham

This article reviews the role of cannabinoids in inhibiting neurodegeneration in models of multiple sclerosis(MS). MS is a chronic, debilitating disease of the central nervous system(CNS), induced by autoimmunity-driven inflammation that leads to demyelination and thus disconnection of the normal transmission of nerve impulses. Despite the use of an array of immune modulating drugs that restore blood brain barrier function, disability continues in patients concomitant with the loss of axons in the spinal cord. MS patients therefore suffer neuropathic pain, spasticity and tremor. Anecdotal evidence suggests that MS patients using cannabis, though illegal, achieve symptomatic relief from neuropathic pain and spasticity associated with MS. The discovery of the endogenous cannabinoid(endocannabinoid) system that naturally exists in the body and which responds to cannabinoids to exert their effects has aided research into the therapeutic utility of cannabinoids. The endocannabinoid system consists of two G-protein coupled receptors cannabinoid receptor type-1(CB1) and CB2.CB1 is mainly expressed in the CNS and CB2 is predominantly found in leukocytes, while an increasing number of potential ligands and endocannabinoid degradation molecules are being isolated. Several studies have highlighted the involvement of this system in regulating neurotransmission and its ability to prevent excessive neurotransmitter release, consistent with a capacity to provide symptomatic relief. In summary, antagonism of the CB1 receptor pathway contributes to neuronal damage in chronic relapsing experimental allergic encephalomyelitis(EAE) and suppresses tremor and spasticity. The addition of exogenous CB1 agonists derived from cannabis also afforded significant neuroprotection from the consequences of inflammatory CNS disease in EAE and experimental allergic uveitis models. Although clear neuroprotective benefits of cannabinoids have been demonstrated, the unwanted psychotropic effects need to be addressed. However, manipulating the endoge

关键词： Multiple sclerosis Axonal damage Neurodegeneration Neuroprotection

求解M-矩阵代数Riccati方程的两种不动点迭代法（英文）

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应用数学 2017年第3期30卷 623-630页

作者：关晋瑞冯月华 zubair ahmed 太原师范学院数学系山西晋中030619 厦门大学数学科学学院福建厦门361005 Institute of Mathematics and Computer Science University of Sindh

M-矩阵代数Riccati方程由于广泛的应用,已成为近年来的热点问题之一,有关其理论和数值方法的研究层出不穷.本文研究M-矩阵代数Riccati方程的数值解法,给出求解其最小非负解的两种新的不动点迭代法.理论分析表明新的不动点迭代法相比现... 详细信息

M-矩阵代数Riccati方程由于广泛的应用,已成为近年来的热点问题之一,有关其理论和数值方法的研究层出不穷.本文研究M-矩阵代数Riccati方程的数值解法,给出求解其最小非负解的两种新的不动点迭代法.理论分析表明新的不动点迭代法相比现有的不动点迭代法收敛速度快,数值实验也验证了新方法的有效性.

关键词： M-矩阵代数Riccati方程最小非负解不动点迭代法