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International Journal of Ophthalmology(English edition) 2018年第1期11卷 117-134页

作者： Mahavir Singh suresh c tyagi Eye and Vision Science Laboratory Department of Physiology University of Louisville School of Medicine

Past 25 y have witnessed an exponential increase in knowledge and understanding of ocular diseases and their respective genetic underpinnings. As a result, scientists have mapped many genes and their variants that can influence vision and health of our eyes. Based on these findings, it is becoming clear that an early diagnosis employing genetic testing can help evaluate patients＇ conditions for instituting treatment plan（s） and follow-up care to avoid vision complications later. For example, knowing family history becomes crucial for inherited eye diseases as it can benefit members in family who may have similar eye diseases or predispositions. Therefore, gathering information from an elaborate examination along with complete assessment of past medical illness by ophthalmologists followed by consultation with geneticists can help create a roadmap for making diagnosis and treatment precise and beneficial. In this review, we present an update on ocular genomic medicine that we believe has tremendous potential towards unraveling genetic implications in ocular diseases and patients＇ susceptibilities. We also discuss translational aspects of genetic ophthalmology and genome engineering that may help advance molecular diagnostics and therapeutics.

关键词： cRISPR/cas9 precision medicine genetic ophthalmology genome engineering inflammation single nucleotide polymorphism

Metalloproteinases as mediators of inflammation and the eyes： molecular genetic underpinnings governing ocular pathophysiology

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International Journal of Ophthalmology(English edition) 2017年第8期10卷 1308-1318页

作者： Mahavir Singh suresh c tyagi Eye and Vision Science Laboratory Department of Physiology University of Louisville School of Medicine Louisville KY 40202 USA

There are many vision threatening diseases of the eye affecting millions of people worldwide. In this article, we are summarizing potential role of various matrix metalloproteinases （MMPs）; the Zn （2＋）-dependent endoproteases in eye health along with pathogenesis of prominent ocular diseases such as macular degeneration, diabetic retinopathy, and glaucoma via understanding MMPs regulation in affected patients, interactions of MMPs with their substrate molecules, and key regulatory functions of tissue inhibitor of metalloproteinases （TIMPs） towards maintaining overall homeostasis.

关键词： age-related macular degeneration choroidal neovascularization diabetes glaucoma metalloproteinases tissue inhibitors of metalloproteinases

Homocysteine mediates transcriptional changes of the inflammatory pathway signature genes in human retinal pigment epithelial cells

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International Journal of Ophthalmology(English edition) 2017年第5期10卷 696-704页

作者： Mahavir Singh suresh c tyagi Department of Physiology University of Louisville School of Medicine Louisville KY 40202 USA

AIM：To test whether homocysteine（Hcy） can influence the transcriptional profile, we hypothesized that Hcy can lead to the induction of proinflammatory molecules in the retinal cells of aging ***：An unbiased in vitro inflammatory pathway focused study was designed employing retinal pigment epithelial（RPE） cell line, ARPE-19. cells were cultured in the presence or absence of Hcy to capture target genes＇ expression profile. Three different concentrations of Hcy were added in the culture medium of confluent monolayers. c RNAs were made from the isolated total RNAs and the labeled c RNA probes were hybridized to microarrays specific for human disease pathway inflammatory cytokines, chemokines and their receptor gene micro-array panels as per manufacture＇s recommendations. Two Hcy up-regulated molecules：IL6 and cEBPB were further validated via Western blot analysis. Hcy＇s effect on ARPE-19 cellular morphology and genomic DNA integrity were also ***：Gene microarray analyses of RPE cells in response to Hcy treatment revealed alterations in the expressions of several inflammatory gene transcripts such as ccL5, cEBPB, IL13RA2, IL15 RA, IL6, IL8 and cXcL3 that were up-regulated. The transcripts for c3, ccL2, IL11 RA and IL18 genes exhibited down-regulation. The IL6 and cEBPB expressions were subsequently validated at the protein levels. Treatment of the retinal cells with increasing Hcy concentration influenced their density in culture however their morphology and DNA integrity remained unaffected. cONcLUSION：These findings suggest that Hcy can potentially mediate the expression of chemokines,cytokines and interleukins receptors in the retinal cells without having any debilitating effects on their morphology and the genomic DNA integrity.

关键词： chemokine choroidal neovascularization cytokine gene expression hyperhomocysteinemia inflammation macular degeneration retinal remodeling

A hypothesis for treating inflammation and oxidative stress with hydrogen sulfide during age-related macular degeneration

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International Journal of Ophthalmology(English edition) 2018年第5期11卷 881-887页

作者： Akash K George Mahavir Singh Rubens Petit Homme Avisek Majumder Harpal S SANDhu suresh c tyagi Eye and Vision Science Laboratory Department of PhysiologyUniversity of Louisville School of Medicine Department of Physiology University of Louisville School of Medicine Department of Biochemistry and Molecular Genetics University of Louisville School of Medicine Department of Ophthalmology and Visual Sciences University of Louisville School of Medicine Kentucky Lions Eye center University of Louisville School of Medicine

Age-related macular degeneration（AMD） is a leading cause of blindness and is becoming a global crisis since affected people will increase to 288 million by ***,age,diabetes,gender,obesity,hypertension,race,hyperopia,iris-color,smoking,sun-light and pyroptosis have varying roles in AMD,but oxidative stress-induced inflammation remains a significant driver of *** is a unique organ as it contains a remarkable oxygengradient that generates reactive oxygen species（ROS） which upregulates inflammatory *** becomes a source of functional and morphological impairments in retinal pigment epithelium（RPE）,endothelial cells and retinal ganglion *** demonstrated that hydrogen sulfide（H2S） acts as a signaling molecule and that it may treat ***,we propose a novel hypothesis that H2S may restore homeostasis in the eyes thereby reducing damage caused by oxidative injury and *** H_2S has been shown to be a powerful antioxidant because of its free-radicals＇ inhibition properties in addition to its beneficial effects in age-relatedconditions,therefore,patients may benefit from H2S salubrious effects not only by minimizing their oxidant and inflammatory injuries to retina but also by lowering retinal glutamate excitotoxicity.

关键词： eye diseases hydrogen sulfide treatment inflammation macula oxidative stress pyroptosis retinal degeneration

Hydrogen sulfide intervention in cystathionine-β-synthase mutant mouse helps restore ocular homeostasis

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International Journal of Ophthalmology(English edition) 2019年第5期12卷 754-764页

作者： Akash K.George Rubens P.Homme Avisek Majumder Anwesha Laha Naira Metreveli Harpal S.SANDhu suresh c.tyagi Mahavir Singh Eye and Vision Science Laboratory University of Louisville School of Medicine Department of Physiology University of Louisville School of Medicine Department of Medicine UCSF Helen Diller Family Comprehensive Cancer CenterUniversity of California San Francisco Department of Ophthalmology and Visual Sciences Kentucky Lions Eye center University of Louisville School of Medicine

AIM: To investigate the applications of hydrogen sulfide(H2 S) in eye-specific ailments in ***: Heterozygous cystathionine-β-synthase(cBS+/-) and wild-type c57 BL/6 J(WT) mice fed with or without high methionine diet(HMD) were administered either phosphate buffered saline(PBS) or the slow-release H2 S donor: GYY4137. Several analyses were performed to study GYY4137 effects by examining retinal lysates for key protein expressions along with plasma glutamate and glutathione estimations. Intraocular pressure(IOP) was monitored during GYY4137 treatment; barium sulfate and bovine serum albumin conjugated fluorescein isothiocyanate(BSA-FITc) angiographies were performed for examining vasculature and its permeability post-treatment. Visionguided behavior was also tested employing novel object recognition test(NORT) and light-dark box test(LDBT) ***: cBS deficiency(cBS+/-) coupled with HMD led disruption of methionine/homocysteine(Hcy) metabolism leading to hyperhomocysteinemia(HHcy) in cBS+/-mice as reflected by increased Hcy, and s-adenosylhomocysteine hydrolase(SAHH) levels. Unlike cBS, cystathionine-γ lyase(cSE), methylenetetrahydrofolate reductase(MTHFR) levels which were reduced but compensated by GYY4137intervention. Heightened oxidative and endoplasmic reticulum(ER) stress responses were mitigated by GYY4137 effects along with enhanced glutathione(GSH) levels. Increased glutamate levels in cBS+/-strain were prominent than WT mice and these mice also exhibited higher IOP that was lowered by GYY4137 treatment. cBS deficiency also resulted in vision-guided behavioral impairment as revealed by NORT and LDBT findings. Interestingly, GYY4137 was able to improve cBS+/-mice behavior together with lowering their glutamate levels. Blood-retinal barrier(BRB) appeared compromised in cBS+/-with vessels' leakage that was mitigated in GYY4137 treated group. This corroborated the results for occludin(an integral plasma membrane protein of the cellular tight

关键词： blood-retinal barrier integrity endoplasmic reticulum stress glutamate cytotoxicity inflammation oxidative stress mice

Phosphorus Starvation Tolerance in Rice Through combined Physiological,Biochemical,and Proteome Analyses

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Rice science 2023年第6期30卷 613-631页

作者： Prathap V suresh KUMAR Nand Lal MEENA chirag MAHESHWARI Monika DALAL Aruna tyagi Division of Biochemistry Indian Council of Agricultural Research-Indian Agricultural Research InstituteNew Delhi 110012India Division of Germplasm Evaluation National Bureau of Plant Genetic ResourcesNew Delhi 110012India National Institute for Plant Biotechnology New Delhi 110012India

Phosphorus(P) deficiency limits the growth,development,and productivity of *** better understand the underlying mechanisms in P-deficiency tolerance and the role of Pup1 QTL in enhancing P use efficiency(PUE) for the development of P-efficient rice cultivars,a pair of contrasting rice genotypes(Pusa-44 and NIL-23) was applied to investigate the morpho-physio-biochemical and proteomic variation under P-starvation *** rice genotypes were grown hydroponically in a PusaRich medium with adequate P(16 mg/kg,+P) or without P(0 mg/kg,-P) for 30 d.P-starvation manifested a significant reductions in root and shoot biomass,shoot length,leaf area,total chlorophyll,and P,nitrogen and starch contents,as well as protein kinase *** stress increased root-to-shoot biomass ratio,root length,sucrose content,and acid phosphatase activity,particularly in the P-tolerant genotype(NIL-23).comparative proteome analysis revealed several P metabolism-associated proteins(including OscDPKs,OsMAPKs,OscPKs,OsLecRK2,and OsSAPks) to be expressed in the shoot of NIL-23,indicating that multiple protein kinases were involved in P-starvation/deficiency ***,the up-regulated expression of OsrbcL,OsABcG32,OsSUS5,OsPoll-like B,and clpc2 proteins in the shoot,and OsAcA9,OsAcA8,OsSPS2F,OsPP2c15,and OsBiP3 in the root of NIL-23,indicated their role in P-starvation stress control through the Pup1 QTL. Thus,our findings indicated that-P stress-responsive proteins,in conjunction with morpho-physio-biochemical modulations,improved PUE and made NIL-23 a P-deficiency tolerant genotype due to the introgression of the Pup1 QTL in the Pusa-44 background.

关键词： phosphorus deficiency Pup1 QTL protein kinase acid phosphatase proteome analysis rice

Seismic wave velocities of rare gas solids through elastic properties in Earth's lower mantle

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Science china Earth Sciences 2009年第10期52卷 1599-1611页

作者： Seema GUPTA suresh c. GOYAL Department of Physics Agra College Faculty of Engineering and Technology Raja Balwant Singh College

The expressions for second (SOE) and third order elastic (TOE) constants for rare gas solids are derived for comparative study of elastic behavior within the framework of many body potentials including the effect of p... 详细信息

关键词： elastic properties seismic wave velocities RGS

current updates on laboratory techniques for the diagnosis of male reproductive failure

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Asian Journal of Andrology 2016年第3期18卷 392-401,I0008页

作者： suresh c Sikka Wayne JG Hellstrom Department of Urology Tulane University School of Medicine New Orleans Louisiana USA.

The incidence of male reproductive failure leading to infertility, whether due to delayed parenthood, environmental issues, genetic factors, drugs, etc., is increasing throughout the world. The diagnosis and prognosis of male subfertility have become a challenge. While the basic semen assessment has been performed for many years, a number of studies question the value of the traditional semen characteristics. This is partly due to inadequate methods and standardization, limited knowledge of technical requirements for quality assurance, and an incomplete understanding of what clinical information a semen assessment can provide. Laboratories currently performing semen and endocrine assessment show great variability. The World Health Organization （WHO） manual for the evaluation of semen has been the core of andrology and fertility evaluation that has helped in further development of this field over many years. These include the physical appearance of the ejaculate, assessments of sperm count, motility, vitality, morphology, and functional aspects of the sperm and semen sample. These tests also include male endocrine profile, biochemical evaluation of the semen, detection of antisperm antibodies in serum, the use of computer-aided sperm analysis （cASA）, sperm DNA integrity, and its damage due to oxidative stress. Assisted reproductive techniques （e.g., IVF, IcSI） have shown great success but are too expensive. Further development in this field with newer techniques and extensive training/instructions can improve accuracy and reduce variability, thus maintaining the quality and standards of such an evaluation. There is an urgent need to have standardized training centers and increased awareness in this area of men＇s health for reproductive success.

关键词： male infertility quality control management reproductive failure semen evaluation World Health Organization manual

Endocrine disruptors and estrogenic effects on male reproductive axis

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Asian Journal of Andrology 2008年第1期10卷 134-145页

作者： suresh c. Sikka Run Wang Department of Urology Tulane University Health Sciences Center New Orleans LA 70112-2699 USA Departments of Urology University of Texas Medical School at Houston and University of Texas MD Anderson Cancer Center Houston TX 77030 USA

Endocrine disruptors （e.g., polychlorinated biphenyls [PcBs], dichlorodiphenyl-trichloroethane [DDT], dioxin, and some pesticides） are estrogen-like and anti-androgenic chemicals in the environment. They mimic natural hormones, inhibit the action of hormones, or alter the normal regulatory function of the endocrine system and have potential hazardous effects on male reproductive axis causing infertility. Although testicular and prostate cancers, abnormal sexual development, undescended testis, chronic inflammation, Sertoli-cell-only pattern, hypospadias, altered pituitary and thyroid gland functions are also observed, the available data are insufficient to deduce worldwide conclusions. The development of intra-cytoplasmic sperm injection （IcSI） is beyond doubt the most important recent breakthrough in the treatment of male infertility, but it does not necessarily treat the cause and may inadvertently pass on adverse genetic consequences. Many well-controlled clinical studies and basic scientific discoveries in the physiology, biochemistry, and molecular and cellular biology of the male reproductive system have helped in the identification of greater numbers of men with male factor problems. Newer tools for the detection of Y-chromosome deletions have further strengthened the hypothesis that the decline in male reproductive health and fertility may be related to the presence of certain toxic chemicals in the environment. Thus the etiology, diagnosis, and treatment of male factor infertility remain a real challenge. clinicians should always attempt to identify the etiology of a possible testicular toxicity, assess the degree of risk to the patient being evaluated for infertility, and initiate a plan to control and prevent exposure to others once an association between occupation/toxicant and infertility has been established.

关键词： endocrine disruptors environmental estogens hypothalamic-pituitary-testicular axis oxidative stress male infertility

Ionic liquid electrolytes for sodium-ion batteries to control thermal runaway

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Journal of Energy chemistry 2023年第6期81卷 321-338,I0008页

作者： Keith Sirengo Aswathy Babu Barry Brennan suresh c.Pillai Nanotechnology and Bio-Engineering Research Group Department of Environmental ScienceAtlantic Technological UniversityATU SligoAsh LaneSligo F91 YW50Ireland Health and Biomedical(HEAL)Strategic Research centre Atlantic Technological UniversityATU SligoAsh LaneSligo F91 YW50Ireland

Sodium-ion batteries are expected to be more affordable for stationary applications than lithium-ion batteries,while still offering sufficient energy density and operational capacity to power a significant segment of the battery *** this,thermal runaway explosions associated with organic electrolytes have led to concerns regarding the safety of sodium-ion *** electrolytes,ionic liquids are promising because they have negligible vapor pressure and show high thermal and electrochemical *** review discusses the safety contributions of these electrolyte properties for high-temperature *** ionic liquids provide thermal stability while at the same time promoting high-voltage window battery ***,apart from cycle stability,there is an additional safety feature attributed to modified ultra-concentrated ionic liquid *** these contributions,the following have been discussed,heat sources and thermal runaway mechanisms,thermal stability,the electrochemical decomposition mechanism of stable cations,and the ionic transport mechanism of ultra-concentrated ionic liquid *** addition,the contributions of hybrid electrolyte systems consisting of ionic liquids with either organic carbonate or polymers are also *** thermal stability of ionic liquids is found to be the main contributor to cell safety and cycle *** high-temperature applications where electrolyte safety,capacity,and cycle stability are important,highly concentrated ionic liquid electrolyte systems are potential solutions for sodium-ion battery applications.

关键词： Thermal stability Ionic liquids Sodium-ion batteries cycle stability Ionic conductivity