Autoimmune epilepsy, retrospective case series of clinical features, management, and outcomes.

OBJECTIVES: To evaluate the clinical and electrographic features of patients with autoimmune epilepsy and assess the influence of early diagnosis and treatment on reducing seizure frequency. METHODS: A retrospective observational case series was conducted utilizing medical records from King Abdullah Medical Hospital between 2017 and 2022. Cases of newly diagnosed seizures were chosen based on laboratory-proven autoimmunity. RESULTS: Five female inpatients were identified, primarily presenting with seizures suggestive of an autoimmune origin. Autoimmune antibodies were detected in all patients as follows: GAD (3), NMDA-R (2). One patient exhibited unilateral temporal lobe onset while three displayed bilateral onset. One patient had an associated malignancy. Rituximab was administered as an immunomodulatory therapy to four patients, resulting in successful seizure reduction post-immunotherapy initiation. CONCLUSION: Autoimmune epilepsy is recognized as a distinct condition. The clinical presentation can be complex and antibody testing may warrant repetition if initial results are negative or if specific antibodies are not detected. Early initiation of immunosuppression, coupled with prompt treatment escalation when required, is vital for achieving optimal patient outcomes.

Coal fly ash application as an eco-friendly approach for modulating the growth, yield, and biochemical constituents of Withania somnifera L. plants.

The solid waste known as fly ash, which is produced when coal is burned in thermal power plants, is sustainably used in agriculture. It is an excellent soil supplement for plant growth and development since it contains some desired nutrients (macro and micro), as well as being porous. The present study was done to evaluate the effect of different fly ash levels on Withania somnifera. The present study aimed to assess the impact of various fly ash (FA) concentrations on growth, yield, photosynthetic pigments, biochemical parameters, and cell viability of W. somnifera. The results showed that FA enhanced physical and chemical properties of soil like pH, electric conductivity, porosity, water-holding capacity, and nutrients. The low doses of FA-amended soil (15%) significantly increased the shoot length (36%), root length (24.5%), fresh weight of shoots and roots (107.8 and 50.6%), dry weight of shoots and roots (61.9 and 47.1%), number of fruits (70.4%), carotenoid (43%), total chlorophyll (44.3%), relative water content (109.3%), protein content (20.4%), proline content (110.3%), total phenols (116.1%), nitrogen (20.3%), phosphorus (16.9%), and potassium (26.4%). On the other hand, the higher doses, i.e., 25% of fly ash showed a negative effect on all the above parameters and induced oxidative stress by increasing lipid peroxidation (33.1%) and hydrogen peroxide (102.0%) and improving the activities of antioxidant enzymes and osmolytes. Compared to the control plants, the plants growing in soil enriched with 15 and 25% fly ash had larger stomata pores when examined using a scanning electron microscope. In addition, according to a confocal microscopic analysis of the roots of W. somnifera, higher fly ash concentrations caused membrane damage, as evidenced by an increase in the number of stained nuclei. Moreover, several functional groups and peaks of the biomolecules represented in the control and 15% of fly ash were alcohols, phenols, allenes, ketenes, isocynates, and hydrocarbons. Gas chromatography-mass spectrometry analysis of the methanol extract of W. somnifera leaves cultivated in soil amended with 15% fly ash shows the presence of 47 bioactive compounds. The most abundant compounds in the methanol extract were cis-9-hexadecenal (22.33%), n-hexadecanoic acid (9.68%), cinnamic acid (6.37%), glycidyl oleate (3.88%), nonanoic acid (3.48%), and pyranone (3.57%). The lower concentrations of FA (15%) can be used to enhance plant growth and lower the accumulation of FA that results in environmental pollution.

Supported nanostructured photocatalysts: the role of support-photocatalyst interactions.

Heterogeneous photocatalysis employing semiconductor oxide photocatalysts is a sustainable and promising method for environmental remediation and clean energy generation. In this context, nanostructured photocatalysts, with at least one dimension in the 1‒100 nm size regime, have attracted ever-growing attention due to their unique and often enhanced size-dependent physicochemical properties. While their reduced size ensures enhanced photocatalytic performance, the same makes it difficult and time/energy-demanding to remove/recover such nanostructured photocatalysts from aqueous media. This fundamental limitation has paved the way towards developing supported nanophotocatalysts where the active photocatalytic nanostructures are coated on the surface of polymeric or inorganic support materials, often in a core@shell conformation. This arrangement solves the problem of photocatalysts' recovery for effective reuse or recycling and leads to improved and desired target properties due to specific photocatalyst-support interactions. While the enhanced physicochemical properties of supported photocatalysts have been widely studied in many target applications, the role of support-photocatalysts interactions in improving these properties remains unexplored. This review article provides an updated viewpoint on the photocatalyst-support interactions and the resulting unique physiochemical properties important for diverse photochemical applications and the design of practical devices. While exploring the properties of supported nanostructured metal oxide/sulfides photocatalysts such as TiO2 and MoS2, we also briefly discuss the common strategies employed to coat the active nanomaterials on the surface of different supports (organic/polymeric, inorganic, active, inert, and magnetic).

Coal fly ash and nitrogen application as eco-friendly approaches for modulating the growth, yield, and biochemical constituents of radish plants.

Plants are confronting a variety of environmental hazards as a result of fast climate change, which has a detrimental influence on soil, plant growth, and nutrient status. As a result, the present study aims to evaluate the influence of various fly ash concentrations (5, 10, 15, 20, 25, 30, and 35% FA) mixed with the optimum concentrations of nitrogen in the form of urea (0.5 g pot-1) on the growth, productivity and biochemical constituents of radish plants. Energy-dispersive X-ray spectroscopy (EDX) and scanning electron microscopy (SEM) were used to assess soil physical-chemical properties and FA nutrient status. Results suggested that FA added many essential plant nutrients to the growth substrate and improved some important soil characteristics such as pH, electric conductivity, porosity, and water holding capacity. Also, the results revealed that the low concentrations of FA up to 20% were found to boost radish growth, yield, chlorophyll, carotenoids, and mineral content. While the highest concentrations of FA (25-35%) decreased radish growth and yield, increased oxidative stress through increased lipid peroxidation (MDA) and caused a significant boost in ascorbic acid, proline, protein, and antioxidant enzyme activities. Furthermore, SEM of radish leaf revealed an enhancement in the stomatal pore of radish leaf under different levels of FA. In conclusion, combining 15% fly ash with 0.5 g nitrogen in the form of urea significantly enhanced radish yield by enhancing antioxidant activity such as catalase, peroxidase, ascorbate peroxidase, Guaiacol peroxidase, superoxide dismutase, nitrate reductase and reducing oxidative stress, potentially reducing fly ash accumulation and environmental pollution.

Key regulatory miRNAs in lipid homeostasis: Implications for cardiometabolic diseases and development of novel therapeutics.

Dysregulation of lipid metabolism is associated with cardiovascular/metabolic diseases, including atherosclerosis, liver diseases and type 2 diabetes mellitus (T2DM). Several miRNAs have been reported as regulators of different stages of lipid homeostasis, including cholesterol/fatty acid biosynthesis, degradation, transport, storage, and low-density (LDL) and high-density lipoprotein (HDL) formation. Indeed, various miRNAs are emerging as attractive therapeutic candidates for metabolic/cardiovascular disease (CVD). Here, we summarize the roles of miR-19b, miR-20a, miR-21, miR-27, miR-29, miR-34a, miR-144, miR-148a, and miR-199a in post-transcriptional regulation of genes involved in lipid homeostasis and their therapeutic potential. We also discuss experimental strategies for further development of these miRNAs as novel cardiometabolic therapeutics.

An evolutionarily-conserved promoter allele governs HMG-CoA reductase expression in spontaneously hypertensive rat.

3-Hydroxy-3-methyl glutaryl-coenzyme A reductase (Hmgcr) encodes the rate-limiting enzyme in the cholesterol biosynthesis pathway. The regulation of Hmgcr in rat models of genetic hypertension (viz. Spontaneously Hypertensive Rat [SHR] and its normotensive control Wistar/Kyoto [WKY] strain) is unclear. Interestingly, Hmgcr transcript and protein levels are diminished in liver tissues of SHR as compared to WKY. This observation is consistent with the diminished plasma cholesterol level in SHR animals. However, the molecular basis of these apparently counter-intuitive findings remains completely unknown. Sequencing of the Hmgcr promoter in SHR and WKY strains reveals three variations: A-405G, C-62T and a 11 bp insertion (-398_-388insTGCGGTCCTCC) in SHR. Among these variations, A-405G occurs at an evolutionarily-conserved site among many mammals. Moreover, SHR-Hmgcr promoter displays lower activity than WKY-Hmgcr promoter in various cell lines. Transient transfections of Hmgcr-promoter mutants and in silico analysis suggest altered binding of Runx3 and Srebf1 across A-405G site. On the other hand, C-62T and -398_-388insTGCGGTCCTCC variations do not appear to contribute to the reduced Hmgcr promoter activity in SHR as compared to WKY. Indeed, chromatin immunoprecipitation assays confirm differential binding of Runx3 and Srebf1 to Hmgcr promoter leading to reduced expression of Hmgcr in SHR as compared to WKY under basal as well as cholesterol-modulated conditions. Taken together, this study provides, for the first time, molecular basis for diminished Hmgcr expression in SHR animals, which may account for the reduced circulating cholesterol level in this widely-studied model for cardiovascular diseases.

Biological control: a novel strategy for the control of the plant parasitic nematodes.

Plant parasitic nematodes (Root-knot nematodes, Meloidogyne spp.) are rounded worms, microscopic, and cause many agricultural economic losses. Their attacks have a direct impact on the productivity of cultivated crops by reducing their fruit quantity. Chemical control is widespread all over the world, but biological control is the most effective way to reduce the number of pests that infect crops, particularly by the use of microorganisms like fungi and bacteria. Biological control is rapidly evolving, and more products are being sold worldwide over time. They can be produced by fungi, bacteria, or actinomycetes that can destruct plant parasite nematodes and feed on them. Nematophagous microorganisms as the natural enemies of nematodes have a promising way of controlling nematodes. Some of them create net-like substances and traps to take the worms from outside and finally kill them. Other parasites serve as internal parasites in order to produce toxins and to produce virulence to kill nematodes. Comprehension of the molecular basis for microbial nematode interactions gives important insights into how successful biological nematode control agents can be created. We discuss recent advances in our understanding of nematodes and nematophagous microorganisms, with an emphasis on molecular mechanisms that infect nematodes with nematophagous microorganisms and on nematode safety from pathogenic attacks. Finally, we addressed numerous key areas for future research and development, including possible approaches to the application of our recent expertise in the development of successful biocontrol strategies.

Impact of the low and high concentrations of fly ash amended soil on growth, physiological response, and yield of pumpkin (Cucurbita moschata Duch. Ex Poiret L.).

Fly ash, a result of coal burning in thermal power plants, is sustainably used in agriculture and has been regarded as a problematic solid waste worldwide. The presence of some desired nutrients (macro and micro) and its porosity makes it a marvelous soil amendment for plant growth and development. The present study was done to evaluate the effect of different fly ash levels on pumpkin crop (Cucurbita moschata). Pot experiment in randomized block design was conducted with different fly ash supplement treatments to analyze the impact of fly ash on growth, chlorophyll, carotenoid, biochemical parameters, and pumpkin crop yield. The results show variation in soil's physical and chemical properties after the application of fly ash (30 and 50%). Also, the lower levels (10-30%) of fly ash amended soil significantly (P ≤ 0.05) enhanced the growth (plant height, plant fresh and dry biomass, no. of leaves, and average area of the leaf), chlorophyll content, and biochemical contents (protein, carbohydrate, mineral, and leaf water content) in pumpkin crop. The proline content was also observed to enhance by the increasing levels of fly ash to soil. The yield parameters in terms of a number of flowers and fruits, fruits' length and diameter, and fresh and dry weight of fruits were also significantly increased in amended soil with 10-30% fly ash. On the other hand, the higher doses, i.e., 40% and 50% of fly ash showed a negative effect and reduced the growth, chlorophyll, carotenoid, biochemical content, proline, and yield in pumpkin crop. We concluded that the lower level of fly ash (up to 30%) could be used as fertilizer in agricultural fields for the improvement of vegetable as well as other food crops in a sustainable manner but the higher level of fly ash (40 and 50%) is toxic to the plant.

Hypoxia-mediated regulation of mitochondrial transcription factors in renal epithelial cells: implications for hypertensive renal physiology.

Kidneys have a high resting metabolic rate and low partial pressure of oxygen due to enhanced mitochondrial oxygen consumption and ATP production needed for active solute transport. Heightened mitochondrial activity leads to progressively increasing hypoxia from the renal cortex to the renal medulla. Renal hypoxia is prominent in hypertensive rats due to increased sodium reabsorption within the nephrons, which demands higher energy production by oxidative phosphorylation (OXPHOS). Consequently, spontaneously hypertensive rats (SHR) display greater oxygen deficiency (hypoxia) than normotensive Wistar Kyoto rats (WKY). Here, we sought to investigate the expression of key proteins for mitochondrial biogenesis in SHR and WKY, and study the regulation of mitochondrial transcription factors (mtTFs) under in vitro hypoxic conditions in renal epithelial cells. We report that renal expressions of hypoxia-inducible factor-1-alpha (HIF-1α), peroxisome proliferator-activated receptor-gamma coactivator-1-alpha (PGC-1α), mtTFs, and OXPHOS proteins are elevated in SHR compared to WKY. In addition, our experiments in cultured kidney cells demonstrate that acute hypoxia augments the expression of these genes. Furthermore, we show that the transcripts of HIF-1α and mtTFs are positively correlated in various human tissues. We reveal, for the first time to our knowledge, that HIF-1α transactivates mtTF genes by direct interaction with their promoters in rat kidney epithelial cells (NRK-52E) under acute hypoxia. Concomitant increases in the mitochondrial DNA and RNA, and OXPHOS proteins are observed. Taken together, this study suggests that hypoxia within the renal epithelial cells may enhance mitochondrial function to meet the energy demand in proximal tubular cells during prehypertensive stages in kidneys of young SHR.

MicroRNA 27a Is a Key Modulator of Cholesterol Biosynthesis.

Hypercholesterolemia is a strong predictor of cardiovascular diseases. The 3-hydroxy-3-methylglutaryl coenzyme A reductase gene (Hmgcr) coding for the rate-limiting enzyme in the cholesterol biosynthesis pathway is a crucial regulator of plasma cholesterol levels. However, the posttranscriptional regulation of Hmgcr remains poorly understood. The main objective of this study was to explore the role of microRNAs (miRNAs) in the regulation of Hmgcr expression. Systematic in silico predictions and experimental analyses reveal that miRNA 27a (miR-27a) specifically interacts with the Hmgcr 3' untranslated region in murine and human hepatocytes. Moreover, our data show that Hmgcr expression is inversely correlated with miR-27a levels in various cultured cell lines and in human and rodent tissues. Actinomycin D chase assays and relevant experiments demonstrate that miR-27a regulates Hmgcr by translational attenuation followed by mRNA degradation. Early growth response 1 (Egr1) regulates miR-27a expression under basal and cholesterol-modulated conditions. miR-27a augmentation via tail vein injection of miR-27a mimic in high-cholesterol-diet-fed Apoe-/- mice shows downregulation of hepatic Hmgcr and plasma cholesterol levels. Pathway and gene expression analyses show that miR-27a also targets several other genes (apart from Hmgcr) in the cholesterol biosynthesis pathway. Taken together, miR-27a emerges as a key regulator of cholesterol biosynthesis and has therapeutic potential for the clinical management of hypercholesterolemia.

Regulation of Monoamine Oxidase B Gene Expression: Key Roles for Transcription Factors Sp1, Egr1 and CREB, and microRNAs miR-300 and miR-1224.

Monoamine oxidase B (MAO-B), a flavoenzyme located in the outer mitochondrial membrane, is involved in the catabolism of monoamines. Altered levels of MAO-B are associated with cardiovascular/neuronal diseases. However, molecular mechanisms of MAO-B gene regulation are partially understood. We undertook a systematic analysis of the MAO-B gene to identify the key transcriptional/post-transcriptional regulatory molecules. Expression of MAO-B promoter-reporter constructs in cultured cells identified the -144/+25-bp domain as the core promoter region. Stringent in silico analysis of this core promoter predicted binding sites for several transcription factors. Over-expression/down-regulation of transcription factors Sp1/Egr1/CREB increased/decreased the MAO-B promoter-reporter activity and endogenous MAO-B protein level. Electrophoretic mobility shift assays and ChIP assays provided evidence for interactions of Sp1/Egr1/CREB with the MAO-B promoter. MAOB transcript level also positively correlated with the transcript level of Sp1/Egr1/CREB in various human tissue samples. Computational predictions using multiple algorithms coupled with systematic functional analysis revealed direct interactions of the microRNAs miR-1224 and miR-300 with MAO-B 3'-UTR. Dopamine dose-dependently enhanced MAO-B transcript and protein levels via increased binding of CREB to MAO-B promoter and reduced miR-1224/miR-300 levels. 8-Bromo-cAMP and forskolin augmented MAO-B expression, whereas inhibition of PKA diminished the gene expression suggesting involvement of cAMP-PKA axis. Interestingly, Sp1/Egr1/CREB/miR-1224 levels correlate with MAO-B expression in rodent models of hypertension/MPTP-induced neurodegeneration, indicating their roles in governing MAO-B gene expression in these disease states. Taken together, this study elucidates the previously unknown roles of the transcription factors Sp1/Egr1/CREB and microRNAs miR-1224/miR-300 in regulating MAO-B gene expression under basal/disease states involving dysregulated catecholamine levels.

A haplotype variant of the human chromogranin A gene (CHGA) promoter increases CHGA expression and the risk for cardiometabolic disorders.

The acidic glycoprotein chromogranin A (CHGA) is co-stored/co-secreted with catecholamines and crucial for secretory vesicle biogenesis in neuronal/neuroendocrine cells. CHGA is dysregulated in several cardiovascular diseases, but the underlying mechanisms are not well established. Here, we sought to identify common polymorphisms in the CHGA promoter and to explore the mechanistic basis of their plausible contribution to regulating CHGA protein levels in circulation. Resequencing of the CHGA promoter in an Indian population (n = 769) yielded nine single-nucleotide polymorphisms (SNPs): G-1106A, A-1018T, T-1014C, T-988G, G-513A, G-462A, T-415C, C-89A, and C-57T. Linkage disequilibrium (LD) analysis indicated strong LD among SNPs at the -1014, -988, -462, and -89 bp positions and between the -1018 and -57 bp positions. Haplotype analysis predicted five major promoter haplotypes that displayed differential promoter activities in neuronal cells; specifically, haplotype 2 (containing variant T alleles at -1018 and -57 bp) exhibited the highest promoter activity. Systematic computational and experimental analyses revealed that transcription factor c-Rel has a role in activating the CHGA promoter haplotype 2 under basal and pathophysiological conditions (viz. inflammation and hypoxia). Consistent with the higher in vitro CHGA promoter activity of haplotype 2, individuals carrying this haplotype had higher plasma CHGA levels, plasma glucose levels, diastolic blood pressure, and body mass index. In conclusion, these results suggest a functional role of the CHGA promoter haplotype 2 (occurring in a large proportion of the world population) in enhancing CHGA expression in haplotype 2 carriers who may be at higher risk for cardiovascular/metabolic disorders.

Functional promoter polymorphisms direct the expression of cystathionine gamma-lyase gene in mouse models of essential hypertension.

Despite the well-known role of cystathionine γ-lyase (Cth) in cardiovascular pathophysiology, transcriptional regulation of Cth remains incompletely understood. Sequencing of the Cth promoter region in mouse models of genetic/essential hypertension (viz. Blood Pressure High [BPH], Blood Pressure Low [BPL] and Blood Pressure Normal [BPN] mice) identified several genetic variations. Transient transfections of BPH/BPL-Cth promoter-reporter plasmids into various cell types revealed higher promoter activity of BPL-Cth than that of BPH-Cth. Corroboratively, endogenous Cth mRNA levels in kidney and liver tissues were also elevated in BPL mice. Computational analysis of the polymorphic Cth promoter region predicted differential binding affinity of c-Rel, HOXA3 and IRF1 with BPL/BPH-Cth promoter domains. Over-expression of c-Rel/HOXA3/IRF1 modulated BPL/BPH-Cth promoter activities in a consistent manner. Gel shift assays using BPH/BPL-Cth-promoter oligonucleotides with/without binding sites for c-Rel/HOXA3/IRF1 displayed formation of specific complexes with c-Rel/HOXA3/IRF1; addition of antibodies to reaction mixtures resulted in supershifts/inhibition of Cth promoter-transcription factor complexes. Furthermore, chromatin immunoprecipitation (ChIP) assays proved differential binding of c-Rel, HOXA3 and IRF1 with the polymorphic promoter region of BPL/BPH-Cth. Tumor necrosis factor-α (TNF-α) reduced the activities of BPL/BPH-Cth promoters to different extents that were further declined by ectopic expression of IRF1; on the other hand, siRNA-mediated down-regulation of IRF1 rescued the TNF-α-mediated suppression of the BPL/BPH-Cth promoter activities. In corroboration, ChIP analysis revealed enhanced binding of IRF1 with BPH/BPL-Cth promoter following TNF-α treatment. BPL/BPH-Cth promoter activity was diminished upon exposure of hepatocytes and cardiomyoblasts to ischemia-like pathological condition due to reduced binding of c-Rel with BPL/BPH-Cth-promoter. Taken together, this study reveals the molecular basis for the differential expression of Cth in mouse models of essential hypertension under basal and pathophysiological conditions.

Molecular mechanism of monoamine oxidase A gene regulation under inflammation and ischemia-like conditions: key roles of the transcription factors GATA2, Sp1 and TBP.

Monoamine oxidase A (MAOA) plays important roles in the pathogenesis of several neurological and cardiovascular disorders. The mechanism of transcriptional regulation of MAOA under basal and pathological conditions, however, remains incompletely understood. Here, we report systematic identification and characterization of cis elements and transcription factors that govern the expression of MAOA gene. Extensive computational analysis of MAOA promoter, followed by 5'-promoter deletion/reporter assays, revealed that the -71/-40 bp domain was sufficient for its basal transcription. Gel-shift and chromatin immunoprecipitation assays provided evidence of interactions of the transcription factors GATA-binding protein 2 (GATA2), Sp1 and TATA-binding protein (TBP) with this proximal promoter region. Consistently, over-expression of GATA2, Sp1 and TBP augmented MAOA promoter activity in a coordinated manner. In corroboration, siRNA-mediated down-regulation of GATA2/Sp1/TBP repressed the endogenous MAOA expression as well as transfected MAOA promoter activity. Tumor necrosis factor-α and forskolin activated MAOA transcription that was reversed by Sp1 siRNA; in support, tumor necrosis factor-α- and forskolin-induced activities were enhanced by ectopic over-expression of Sp1. On the other hand, MAOA transcription was diminished upon exposure of neuroblasts or cardiac myoblasts to ischemia-like conditions because of reduced binding of GATA2/Sp1/TBP with MAOA promoter. In conclusion, this study revealed previously unknown roles of GATA2, Sp1 and TBP in modulating MAOA expression under basal as well as pathophysiological conditions such as inflammation and ischemia, thus providing new insights into the molecular basis of aberrant MAOA expression in neuronal/cardiovascular disease states. Dysregulation of monoamine oxidase A (MAOA) have been implicated in several behavioral and neuronal disease states. Here, we identified three crucial transcription factors (GATA2, Sp1 and TBP) that regulate MAOA gene expression in a coordinated manner. Aberrant MAOA expression under pathophysiological conditions including inflammation and ischemia is mediated by altered binding of GATA2/Sp1/TBP with MAOA proximal promoter. Thus, these findings provide new insights into pathogenesis of several common diseases. GATA2, GATA-binding protein 2; Sp1, specificity protein 1; TBP, TATA-binding protein.

Transcriptional regulation of the novel monoamine oxidase renalase: Crucial roles of transcription factors Sp1, STAT3, and ZBP89.

Renalase, a novel monoamine oxidase, is emerging as an important regulator of cardiovascular, metabolic, and renal diseases. However, the mechanism of transcriptional regulation of this enzyme remains largely unknown. We undertook a systematic analysis of the renalase gene to identify regulatory promoter elements and transcription factors. Computational analysis coupled with transfection of human renalase promoter/luciferase reporter plasmids (5'-promoter-deletion constructs) into various cell types (HEK-293, IMR32, and HepG2) identified two crucial promoter domains at base pairs -485 to -399 and -252 to -150. Electrophoretic mobility shift assays using renalase promoter oligonucleotides with and without potential binding sites for transcription factors Sp1, STAT3, and ZBP89 displayed formation of specific complexes with HEK-293 nuclear proteins. Consistently, overexpression of Sp1, STAT3, and ZBP89 augmented renalase promoter activity; additionally, siRNA-mediated downregulation of Sp1, STAT3, and ZBP89 reduced the level of endogenous renalase transcription as well as the transfected renalase promoter activity. In addition, chromatin immunoprecipitation assays showed in vivo interactions of these transcription factors with renalase promoter. Interestingly, renalase promoter activity was augmented by nicotine and catecholamines; while Sp1 and STAT3 synergistically activated the nicotine-induced effect, Sp1 appeared to enhance epinephrine-evoked renalase transcription. Moreover, renalase transcript levels in mouse models of human essential hypertension were concomitantly associated with endogenous STAT3 and ZBP89 levels, suggesting crucial roles for these transcription factors in regulating renalase gene expression in cardiovascular pathological conditions.