Arsenic Induced Oxidative Neural-Damages in Rat are Mitigated by Tea-Leave Extract via MMPs and AChE Inactivation, Shown by Molecular Docking and in Vitro Studies with Pure Theaflavin and AChE.

BACKGROUND: Chronic arsenic-exposure causes neuromuscular disorders and other health anomalies. Damage to DNA and cytoskeletal/extracellular matrix is brought on by reactive-oxygen-species (ROS)-induced intrinsic antioxidant depletion (thiols/urate). Therapeutic chelating-agents have multiple side-effects. OBJECTIVES: The protection of (Camellia sinensis) tea-extract and role of uric-acid (UA) or allopurinol (urate-depletor) on arsenic-toxicity were verified in rat model. METHODS: Camellia sinensis (CS dry-leaves), UA or allopurinol was supplemented to arsenic-intoxicated rats for 4-weeks. Purified theaflavins and their galloyl-ester were tested in-vitro on pure AChE (acetylcholinesterase) and their PDB/PubChem 3-D structures were utilized for in-silico binding studies. The primary chemical components were evaluated from CS-extracts. Biochemical analysis, PAGE-zymogram, DNA-stability comet analysis, HE-staining was performed in arsenic-exposed rat brain tissues. RESULTS: Animals exposed to arsenic showed symptoms of erratic locomotion, decreased intrinsic antioxidants (catalase/SOD1/uric acid), increased AChE, and malondialdehyde. Cerebellar and cerebrum tissue damages were shown with increased levels of matrix-metalloprotease (MMP2/9) and DNA damage (comets). Allopurinol- supplemented group demonstrated somewhat similar biochemical responses. In the CS-group brain tissues especially cerebellum is considerably protected which is evident from endogenous antioxidant and DNA and cytoskeleton protection with concomitant inactivation of MMPs and AChE. Present study indicates theaflavin-digallate (TFDG) demonstrated the highest inhibition of purified AChE (IC50 = 2.19 µg/ml with the lowest binding free-energy; -369.87 kcal/mol) followed by TFMG (IC50 = 3.86 µg/ml, -347.06 kcal/mol) suggesting their possible restoring effects of cholinergic response. CONCLUSIONS: Favorable responses in UA-group and adverse outcome in allo-group justify the neuro-protective effects of UA as an endogenous antioxidant. Role of flavon-gallate in neuro protection mechanism may be further studied.

Copper-independent lysosomal localisation of the Wilson disease protein ATP7B.

In hepatocytes, the Wilson disease protein ATP7B resides on the trans-Golgi network (TGN) and traffics to peripheral lysosomes to export excess intracellular copper through lysosomal exocytosis. We found that in basal copper or even upon copper chelation, a significant amount of ATP7B persists in the endolysosomal compartment of hepatocytes but not in non-hepatic cells. These ATP7B-harbouring lysosomes lie in close proximity of ~10 nm to the TGN. ATP7B constitutively distributes itself between the sub-domain of the TGN with a lower pH and the TGN-proximal lysosomal compartments. The presence of ATP7B on TGN-lysosome colocalising sites upon Golgi disruption suggested a possible exchange of ATP7B directly between the TGN and its proximal lysosomes. Manipulating lysosomal positioning significantly alters the localisation of ATP7B in the cell. Contrary to previous understanding, we found that upon copper chelation in a copper-replete hepatocyte, ATP7B is not retrieved back to TGN from peripheral lysosomes; rather, ATP7B recycles to these TGN-proximal lysosomes to initiate the next cycle of copper transport. We report a hitherto unknown copper-independent lysosomal localisation of ATP7B and the importance of TGN-proximal lysosomes but not TGN as the terminal acceptor organelle of ATP7B in its retrograde pathway.

Superiority of the Supramolecular Halogen Bond Receptor over Its H-Bond Analogue toward the Efficient Extraction of Perrhenate from Water.

A halogen bond-based water-soluble tetrapodal iodoimidazolium receptor, (L-I)(4Br), exhibited a high degree of efficiency (∼96%) in extracting ReO4- from 100% aqueous medium within a wide range of concentrations and of pH values along with excellent reusability. The solid-state X-ray diffraction study showed the trapping of ReO4- by (L-I)(4Br) via the Re-O····I halogen bonding interaction. XPS studies also suggested the interaction between I and ReO4- through polarization of the electron density of I atoms by ReO4-. (L-I)(4Br) is found to be capable of retaining its high extraction efficiency in the presence of competing anions such as F-, Cl-, I-, SO42-, H2PO4-, CO32-, NO3-, BF4-, ClO4-, Cr2O72-, and a mixture of these anions. Interestingly, (L-I)(4Br) was found to be superior in ReO4- extraction as compared to its hydrogen-bond donor analogue, (L-H)(4Br), as confirmed by a series of control experiments and theoretical calculations. Our synthesized dipodal and tripodal halogen bond donor receptors and their H-analogues validated the superiority of these classes of supramolecular halogen bond donor receptors over their hydrogen-bond analogues. (L-I)(4Br) also showed superior practical applicability in terms of the removal of ReO4- at anion concentrations as low as ∼100 ppm, which was a major shortcoming of (L-H)(4Br).

Role of aspirin activated nitric oxide synthase in controlling DOCA-salt-induced hypertension in rats through the stimulation of renal r-cortexin in kidney cortex cells.

Objectives: Because the damage of kidney tissue is associated with hypertension and impaired nitric oxide (NO) synthesis, and as aspirin is reported to stimulate the synthesis of renal r-cortexin, an anti-hypertensive protein, we investigated the role of aspirin as bolus dose on elevated blood pressure induced by deoxycorticosterone acetate (DOCA)-salt in animal model. Methods: The chronic antihypertensive effect of aspirin on DOCA treated with ASA group of rats (n = 6) was evaluated after ingestion of 0.35 µM aspirin as a bolus dose in every 24 h using tail cuff methods. The plasma aspirin, NO, and r-cortexin levels were determined by spectrophotometric, methemoglobin, and ELISA methods, respectively. Synthesis of r-cortexin mRNA was determined. Aspirin activated nitric oxide synthase (AANOS) was purified by chromatographic methods. Results: Our results showed after 3 h of administration of aspirin (0.35 µM) to the DOCA treated with ASA group of rats decreased the systolic blood pressure from 139.39 ± 7.36 mm of Hg to 116.57 ± 6.89 mm of Hg and diastolic blood pressure from 110.4 ± 7 mm of Hg to 86.4 ± 2.76 mm of Hg. The reduction of BPs was found to be related to the increased plasma aspirin from 0.00 µM to 0.042 µM, plasma NO from 0.4 ± 0.19 nM to 1.9 ± 0.5 nM, and cortexin levels from 64.36 ± 12.6 nM to 216.7 ± 21.3 nM. The molecular weight of purified AANOS is 18 kDa. Conclusion: It can be concluded that aspirin possesses antihypertensive effect on blood pressure in chronic administration. Aspirin can stimulate NO synthesis through the activation of AANOS, which stimulated the production of r-cortexin in kidney cortex cells and thereby reducing elevated BP in hypertensive rats.

Application of coke breeze for removal of colour from coke plant wastewater.

Treatment of coking waste water has always been a challenge because of its complex and toxic nature. Numbers of technologies like biological treatment, advanced oxidation processes, activated carbon treatment etc. are available for removal of color and organic contaminants from wastewater. However, challenges and problems associated with application of biological, advanced oxidation methods for removal of color, chemical oxygen demand (COD), cyanides led to thrust for the development of new promising technologies. In this study, the application of coke breeze for the treatment of wastewater through adsorption has been demonstrated. A pseudo second order reaction kinetics has been observed through batch process adsorption study. Furthermore, adsorption data has found to be best fitted with the Freundlich adsorption isotherm model. Color removal efficiency of 80-90% along with COD removal efficiency of 40-50% was observed within 30 min by 120 g/L dosage of the adsorbent. The removal of phenolic and other organic compounds from coking wastewater has been measured through UV-Vis spectroscopy. The morphological changes of the adsorbent coke breeze have been captured through scanning electron microscopy (SEM) and energy dispersive X-ray (EDX) analysis. However, because of the significant abundance in the steel plant, cost effectiveness and applicability of the post-treated coke breeze in sintered plant as fuel, turn it into a suitable adsorbent despite of having much lower specific surface area compared to commercial activated carbon (AC). Therefore, application of the coke breeze turns it into a very promising material and the technique is sustainable towards the coke quenching effluent treatment.

Poisson Counts, Square Root Transformation and Small Area Estimation: Square Root Transformation.

The paper intends to serve two objectives. First, it revisits the celebrated Fay-Herriot model, but with homoscedastic known error variance. The motivation comes from an analysis of count data, in the present case, COVID-19 fatality for all counties in Florida. The Poisson model seems appropriate here, as is typical for rare events. An empirical Bayes (EB) approach is taken for estimation. However, unlike the conventional conjugate gamma or the log-normal prior for the Poisson mean, here we make a square root transformation of the original Poisson data, along with square root transformation of the corresponding mean. Proper back transformation is used to infer about the original Poisson means. The square root transformation makes the normal approximation of the transformed data more justifiable with added homoscedasticity. We obtain exact analytical formulas for the bias and mean squared error of the proposed EB estimators. In addition to illustrating our method with the COVID-19 example, we also evaluate performance of our procedure with simulated data as well.

Superiority of a polymeric scavenger over its hexapodal monomer towards efficient ReO4- removal in water.

A new imidazolium functionalized hexapodal polymeric receptor, [PHIm-Br], showed selective and efficient removal (>99%) of perrhenate (ReO4-), from 100% aqueous medium via solid-liquid extraction, which was 13% higher as compared to its monomeric analouge [HIm-Br]. Most importantly, [PHIm-Br] overcomes the drawback of [HIm-Br] in terms of removal of ReO4- at lower anion concentration of ∼100 ppm along with excellent radiation resistivity and reusability within a wide pH range, which implies its potential towards practical applications.

Gut Microbe-Derived Outer Membrane Vesicles: A Potential Platform to Control Cecal Load of Campylobacter jejuni.

Acute diarrheal illness and gastroenteritis caused by Campylobacter jejuni infection remain significant public health risks in developing countries with substantial mortality and morbidity in humans, particularly in children under the age of five. Genetic diversities among Campylobacter jejuni and limited understanding of immunological correlations of host protection remain primary impediments for developing an effective measure to controlCampylobacter infection. Moreover, the lack of a reliable in vivo model to mimic natural infection against Campylobacter jejuni has substantially delayed the vaccine-development process. Given the role of bacterial outer membrane associated proteins in intestinal adherence and invasion as well as modulating dynamic interplay between host and pathogens, bacterial outer-membrane vesicles have emerged as a potential vaccine target against a number of gut pathogens, including Campylobacter jejuni. Here, we describe a mucosal vaccine strategy using chitosan-coated outer-membrane vesicles to induce specific immune responses against Campylobacter jejuni in mice. To overcome the challenges of mucosal delivery of outer membrane vesicles in terms of exposure to variable pH and risk of enzymatic degradation, we preferentially used chitosan as a nontoxic, mucoadhesive polymer. We show that intragastric delivery of chitosan-coated outer-membrane vesicles imparts significant immune protection against Campylobacter jejuni with high level local and systemic antibody production. Further, immunization with the outer membrane vesicles resulted in potent cellular responses with an increased CD4+ and CD8+ T cell population. Moreover, significant upregulation of IFN-γ and IL-6 gene expression suggests that mucosal delivery of outer membrane vesicles promotes a Th1/Th2 mixed-type immune response. Together, as an acellular and nonreplicating canonical end product of bacterial secretion, mucosal delivery of outer membrane vesicles may represent a promising platform for developing an effective vaccine againstCampylobacter jejuni.

Stabilization of uranyl(v) by dipicolinic acid in aqueous medium.

Preparation of a stable U(v) complex in an aqueous medium is a challenging task owing to its disproportionation nature (conversion into more stable U(vi) and U(iv) species) and sensitivity to atmospheric oxygen. The stable uranyl (UO22+)/dipicolinic acid (DPA) complex ([U(VI)O2(DPA)(OH)(H2O)]-) was formed at pH 10.5-12.0, which was confirmed by potentiometric and spectrophotometric titrations, and NMR, ESI-MS and EXAFS spectroscopy. The complex [U(VI)O2(DPA)(OH)(H2O)]- can be electrochemically reduced on the Pt electrode at -0.9 eV (vs. Ag/AgCl) to [U(V)O2(DPA)(OH)(H2O)]2- in aqueous medium under an anaerobic environment. According to cyclic voltammetric analysis, a pair of oxidation and reduction waves at E'0 = -0.592 V corresponds to the [U(VI)O2(DPA)(OH)(H2O)]-/[U(V)O2(DPA)(OH)(H2O)]2- redox couple and the formation of [U(V)O2(DPA)(OH)(H2O)]2- was confirmed by the electron stoichiometry (n = 0.97 ± 0.05) of the reduction reaction of [U(VI)O2(DPA)(OH)(H2O)]-. The pentavalent uranyl complex [U(V)O2(DPA)(OH)(H2O)]2- was further characterized via UV-vis-NIR absorption spectrophotometry and X-ray absorption (XANES and EXAFS) spectroscopy. The [U(V)O2(DPA)(OH)(H2O)]2- complex is stable at pH 10.5-12.0 in anaerobic water for a few days. DFT calculation shows the strong complexing ability of DPA stabilizing the unstable oxidation state U(v) in aqueous medium.

Breast cancer pathogenesis is linked to the intra-tumoral estrogen sulfotransferase (hSULT1E1) expressions regulated by cellular redox dependent Nrf-2/NFκß interplay.

BACKGROUND: Estrogen sulfotransferase catalyzes conjugation of sulfuryl-group to estradiol/estrone and regulates E2 availability/activity via estrogen-receptor or non-receptor mediated pathways. Sulfoconjugated estrogen fails to bind estrogen-receptor (ER). High estrogen is a known carcinogen in postmenopausal women. Reports reveal a potential redox-regulation of hSULT1E1/E2-signalling. Further, oxidatively-regulated nuclear-receptor-factor 2 (Nrf2) and NFκß in relation to hSULT1E1/E2 could be therapeutic-target via cellular redox-modification. METHODS: Here, oxidative stress-regulated SULT1E1-expression was analyzed in human breast carcinoma-tissues and in rat xenografted with human breast-tumor. Tumor and its surrounding tissues were obtained from the district-hospital. Intracellular redox-environment of tumors was screened with some in vitro studies. RT-PCR and western blotting was done for SULT1E1 expression. Immunohistochemistry was performed to analyze SULT1E1/Nrf2/NFκß localization. Tissue-histoarchitecture/DNA-stability (comet assay) studies were done. RESULTS: Oxidative-stress induces SULT1E1 via Nrf2/NFκß cooperatively in tumor-pathogenesis to maintain the required proliferative-state under enriched E2-environment. Higher malondialdehyde/non-protein-soluble-thiol with increased superoxide-dismutase/glutathione-peroxidase/catalase activities was noticed. SULT1E1 expression and E2-level were increased in tumor-tissue compared to their corresponding surrounding-tissues. CONCLUSIONS: It may be concluded that tumors maintain a sustainable oxidative-stress through impaired antioxidants as compared to the surrounding. Liver-tissues from xenografted rat manifested similar E2/antioxidant dysregulations favoring pre-tumorogenic environment.

Selective and efficient removal of perrhenate by an imidazolium based hexapodal receptor in water medium.

This work reports a new cationic imidazolium based hexapodal receptor, [L.6Br], for selective and efficient removal of perrhenate (ReO4-) as [L.6ReO4] from 100% aqueous medium via extraction through precipitation. Selective removal of ReO4- even in the presence of common anions such as halides and oxyanions in excess within a wide range of pH values from 1 to 14 by this receptor is also demonstrated. Importantly, [L.6Br] could easily be recovered upon heating [L.6ReO4] with tetrabutylammonium bromide (TBABr) in acetonitrile at 60 °C and recycled as a fresh extractant for ReO4-.

Neurotoxic Mechanism of Arsenic: Synergistic Effect of Mitochondrial Instability, Oxidative Stress, and Hormonal-Neurotransmitter Impairment.

Arsenic toxicity which is now a global concern is predicted to affect more than 200 million people. Chronic arsenic exposure conduce carcinogenicity, hepatotoxicity, and neurotoxicity. Here we have reviewed numerous epidemiological and experimental reports related to arsenic toxicity to explore its neurotoxicity mechanism. Penetrability of this metalloid through blood-brain barrier makes it a potent neuro-toxicant by inducing mitochondrial membrane instability and calorie exhaustion. It directly affects the cortex, cerebellum region, and specially microglial cells by the induction of a variety of pro-inflammatory cytokines like TNF-α, IL-6, etc. Pro-apoptotic signaling and the caspase activation by arsenic initiate large-scale tissue damage. Severe diminution of the antioxidant enzymes like superoxide dismutase, catalase, and GPx increases the tissue damage by reactive oxygen and nitrogen species. Hormonal imbalance and neurotransmitter dysregulations make the neural damage and synergism of so many toxic effects create nonresponsive neural control over multiple organs. That enhances the peripheral major organ damage besides direct arsenic effects on these organs. There is motor and cognitive dysfunction which may initiate Parkinsonism- and Alzheimer's-like symptoms. Our present analysis is helpful for the therapeutic studies on arsenic or other heavy metal associated neurological dysfunction.

Supramolecular Self-Assembly Driven Selective Sensing of Phosphates.

A new bis-heteroleptic RuII complex (1[PF6]2) with iodotriazole as the anion binding group along with the attached pyrene moiety is developed to investigate anion sensing properties and the origin of its selectivity toward a particular class of anions. Selective sensing of phosphates over other anions in both the solution and solid states by 1[PF6]2 is clearly evident from the perturbation of the absorption band and a large degree of amplification of 3MLCT emission band in the presence of phosphates. Importantly, macroscopic investigation such as Scanning Electron Microscopy (SEM) and Dynamic Light Scattering (DLS) indicated the formation of supramolecular architecture in the presence of dihydrogen phosphate via halogen bonding interaction and π-π stacking of pyrene moieties. Such macroscopic property is further corroborated by solution and solid state spectroscopic studies, e.g., 1H-DOSY NMR, single crystal X-ray crystallography, and solid state photoluminescence (PL) spectroscopy.

Cu(ii) templated formation of [n]pseudorotaxanes (n = 2, 3, 4) using a tris-amino ether macrocyclic wheel and multidentate axles.

A tris-amine and oxy-ether functionalised macrocyclic wheel (NaphMC) and various phenanthroline based multidentate axles (L1, L2 and L3) are utilised for the formation of [n]pseudorotaxanes (n = 2, 3, 4) in high yields via Cu(ii) temptation and π-π stacking interactions. The systematic development of threaded supramolecular architectures i.e. [2]pseudorotaxane {[2]CuPR(ClO4)2}, [3]pseudorotaxane {[3]CuPR(ClO4)4} and [4]pseudorotaxane {[4]CuPR(ClO4)6} from bidentate L1, linear tetradentate L2 and tripodal hexadentate L3 respectively is described. All the [n]pseudorotaxanes are well characterized by several spectroscopy and other experimental techniques such as electrospray ionization mass spectrometry (ESI-MS), isothermal titration calorimetric (ITC) study, UV/Vis, EPR, IR and elemental analysis. Moreover, the single crystal X-ray analysis of [2]pseudorotaxane confirmed the threading of L1 in the cavity of NaphMC, resulting in the formation of a penta-coordinated Cu(ii) ternary complex. ITC studies revealed the order of binding constant values for the formation of [n]pseudorotaxanes from the NaphMC-Cu(ii) complex and multidentate axles as L3 > L2 > L1. Finally, we have also shown the ability of Ni(ii) to act as a metal template in the formation of [n]pseudorotaxanes.

An integrated urea and halogen bond donor based receptor for superior and selective sensing of phosphates.

A new RuII based bis-heteroleptic ditopic receptor, 1[PF6]2 (C44H33F12IN10OP2Ru), having integrated anion binding iodotriazole (halogen bond donor) and urea units (-NH bond donor) is employed for selective sensing of phosphates (e.g., H2PO4- and HP2O73-). 1[PF6]2 showed superiority in phosphate sensing in CH3CN as compared to its hydrogen bond donor analogue, 2[PF6]2 (C44H34F12N10OP2Ru), non-urea halogen bond analogue, 3[PF6]2 (C38H27F12IN8P2Ru) and non-urea hydrogen bond donor analogue, 4[PF6]2 (C38H28F12N8P2Ru) in terms of enhanced binding constant values, longer excited state lifetimes and lower detection limit values. 1H-NMR, Isothermal Titration Calorimetry (ITC) and photophysical studies revealed the implementation of the combined role of both the halogen bond donor iodotriazole unit and the -NH unit of the urea moiety for selective and enhanced binding of phosphates.

A multifunctional catenated host for the efficient binding of Eu3+ and Gd3.

A new multifunctional [2]catenane is synthesized by using a phenanthroline-based heteroditopic wheel and Axle, which acts as a receptor for the efficient binding of lanthanide ions such as Eu3+ and Gd3+.

Enantioselective radical conjugate additions driven by a photoactive intramolecular iminium-ion-based EDA complex.

The photochemical activity of electron donor-acceptor (EDA) complexes provides a way to generate radicals under mild conditions. This strategy has found application in chemical synthesis and recently in enantioselective catalysis. Reported methods classically relied on the formation of intermolecular EDA complexes, generated upon aggregation of two suitable reagents. Herein, we further expand the synthetic utility of this strategy demonstrating that an intramolecular EDA complex can trigger a photochemical catalytic enantioselective radical process. This approach enables radical conjugate additions to ß-substituted cyclic enones to form quaternary carbon stereocenters with high stereocontrol using visible light irradiation. Crucial for success is the use of an amine catalyst, adorned with a carbazole moiety, which generates, upon condensation with enones, chiral iminium ions that show a broad absorption band in the visible region. This optical property originates from an intramolecular charge transfer π-π interaction between the electron-rich carbazole nucleus and the electron-deficient iminium double bond.

Balancing the acidity of the pendant urea arm of bis-heteroleptic ruthenium(ii) complex containing pyridyl triazole for improved oxyanion recognition.

Two new RuII-based bis-heteroleptic ditopic receptors 1[PF6]2 (C44H34F12N10OP2Ru) and 2[PF6]2 (C40H27F17N10OP2Ru), decorated with a 1-naphthyl and pentafluorophenyl urea pendant arm, respectively, along with the previously reported 3[PF6]2 (C40H31F13N10OP2Ru), containing a pendant 4-fluorophenyl urea unit and 4[PF6]2, devoid of a pendant urea arm, have been studied to establish the role of urea proton acidity on the sensing and extraction of oxyanions in the presence of triazole C-H as an additional hydrogen bonding motif. 1H-NMR, isothermal titration calorimetry (ITC) and photophysical experiments show selective binding of 1[PF6]2 and 2[PF6]2 toward oxyanions such as phosphates (e.g., H2PO4- and HP2O73-) and carboxylates (e.g., CH3CO2- and PhCO2-) like 3[PF6]2. This generalizes the role of triazole C-H and urea in the RuII-based bis-heteroleptic ditopic receptors towards recognition of such anions. Interestingly, complex 1[PF6]2 having intermediate acidic urea -NH protons showed the highest binding affinity with phosphates as compared to the other urea analogues 2[PF6]2 and 3[PF6]2 as well as the non-urea analogue, 4[PF6]2 (C32H24F12N8P2Ru). Moreover, 2[PF6]2 having the most acidic -NH protons showed higher binding affinity towards carboxylates as compared to that of 1[PF6]2/3[PF6]2. Detailed photo-physical studies revealed that 1[PF6]2 is a farsuperior and more selective H2PO4- sensor compared to 2[PF6]2/3[PF6]2/4[PF6]2, as evidenced by the higher degree of amplification of RuII center-based MLCT emission, greater change in excited state lifetime, lower detection limit and higher degree of selectivity. Furthermore, 1[PF6]2 also acts as a moderate liquid-liquid extraction agent of H2PO4-, CH3CO2- and PhCO2- anions, which was comparable to 3[PF6]2 and much higher as compared to 2[PF6]2/4[PF6]2.

Role of Acetyl Salicylic Acid in Controlling the DOCA-Salt Induced Hypertension in Rats by Stimulating the Synthesis of r-Cortexin in the Kidney.

INTRODUCTION: Hypertension is a metabolic disease which is caused by vasoconstriction and that results into elevated blood pressure. A chronic hypertensive condition affects and even damages to various systems in the body. Presence of renal cortexin (r-cortexin), an antihypertensive protein, which is released from the kidney cortex controls the blood pressure. The effect of r-cortexin was mediated through nitric oxide (NO), a universal vasodilating agent. AIM: In our study, acetyl salicylic acid (aspirin), a well-known activator of the endothelial nitric oxide synthase (eNOS) induced r-cortexin synthesis. METHODS: The hypertensive rat model was prepared by injecting deoxy corticosterone acetate (DOCA). Synthesis of r-cortexin was measured by the anti-r-cortexin antibody which was raised in adult white Wister albino rat model. NO level was determined by using methemoglobin method and later confirmed by chemiluminescence method. Change in blood pressure was determined indirectly by using NIBP monitoring system. RESULTS: Aspirin increased the r-cortexin expression from 64.36 ± 12.6 nM to 216.7 ± 21.31 nM in DOCA induced hypertensive rats. The mechanism was proved with the findings of increased level of NO from 0.4 to 1.9 µM. The DOCA induced blood pressure was also decreased from 139.39 ± 7.36 mm of Hg to 116.57 ± 6.89 mm of Hg in case of systolic blood pressure and in case of diastolic pressure from 110.41 ± 7 mm of Hg to 86.4 ± 2.76 mm of Hg that are quite approximate. CONCLUSION: So, from this study it has been found that aspirin induces the r-cortexin synthesis in kidney cortex through the activation of eNOS in DOCA induced hypertensive rats.

Mechanistic Insight into Fast and Highly Efficient Organocatalytic Activity of a Tripodal Dimeric Hexaurea Capsular Assembly in Michael Addition Reactions.

A tris(2-aminoethyl)-amine-based dimeric capsular assembly of pentafluorophenyl urea (C1) has been employed as a catalyst in a wide range of Michael addition reactions. This capsular catalyst assembly dramatically accelerates the Michael addition reaction of ß-nitrostyrenes (2a-2d) with various Michael donors such as ketoesters (3a, 3e), 1,3-diketones (3b), diesters (3C), and cyanoesters (3d) at room temperature to yield the corresponding nitroalkanes in significantly high yields within a very short reaction time. Significant improvement in solubility and use of conventional organic solvents in reaction along with a drastic decrease in reaction time (high value of the rate constant of the reaction) has been achieved through C1 as compared to the previously reported homologous tripodal monomeric urea catalyst (L1). The addition of enolate to ß-nitrostyrenes to generate an anionic intermediate seemed to be highly stabilized by the six urea units of capsular assembly. Control experiments and in situ kinetic studies are performed for this addition reaction and based on the results, a plausible mechanism has been proposed for the formation of Michael adduct inside the capsular cavity.