Modeling the structure and reactivity landscapes of a pyrazole-ammonium ionic derivative using wavefunction-dependent characteristics and screening for potential anti-inflammatory activity.

Spectroscopic investigations of 1-phenyl -2,3-dimethyl-5-oxo-1,2-dihydro-1H-pyrazol-4-ammonium 2[(2-carboxyphenyl) disulfanyl]benzoate (PACB) reported experimentally and theoretically. NH-O interaction is observed and there is a very large downshift for NH-O stretching frequency. Reactive sites are identified from the chemical and electronic properties. For PACB the maximum repulsion was around H33, H55 and H57 atom. LOL shows red regions between C-C and blue around C atoms are surrounded by a delocalized electron cloud. The red ring is a hallmark of electron density depletion from the NCI plot due to electrostatic repulsion and its existences suggests that coordination sphere for PACB is minimally strained around the central ion. Atomic contact energy values and high score of the docking results obtained propose that, PACB may have inhibitory properties and have a significant function in pharmacological chemistry. Molecular dynamics simulation was performed to validate the stability of the title compound with the Bovine thrombin-activatable fibrinolysis inhibitor protein.Communicated by Ramaswamy H. Sarma.

Computational investigation, comparative approaches, molecular structural, vibrational spectral, non-covalent interaction (NCI), and electron excitations analysis of benzodiazepine derivatives.

The present work explores the structural parameters and vibrational frequencies as well as molecular interactions of benzodiazepine derivatives, such as clothiapine (CT), clozapine (CZ), and loxapine (LX). Employing fitting experimental data to theoretical results is used to assess the structural parameters of heading composites. The main assignment is passed out according to the overall distribution of energy of the vibrational modes. From the hyper-conjugative interaction, the permanency of the structure had been predicted through natural bond orbital analysis; it is also used to identify the bonding and antibonding regions of the molecules. Moreover, electrostatic potential (ESP), density of states (DOS), and charge transfer occurring of the molecule among HOMO as well as LUMO energy were calculated and presented; utilizing electron localized field (ELF), localized orbital locator (LOL), and reduced density gradient (RDG), the chemical interactive regions are found. Additionally, mean polarizability (αtot), the first-order hyperpolarizability (ßtot), and softness and hardness of the entitled compounds were also performed. The interaction between protein-ligand was also predicted by docking studies.

Modeling the structural and reactivity properties of hydrazono methyl-4H-chromen-4-one derivatives-wavefunction-dependent properties, molecular docking, and dynamics simulation studies.

This study explains the vibration and interaction of three pharmaceutically active hydrazine derivatives, (E)-3-((2-(2,5-difluorophenyl)hydrazono)methyl)-4H-chromen-4-one (DFH), (E)-3-((2-(4-(trifluoromethyl)phenyl)hydrazono)methyl)-4H-chromen-4-one (TMH), and (E)-3-((2-(3,5-bis(trifluoromethyl)phenyl)hydrazono)methyl)-4H-chromen-4-one (BPH) using theoretical approach. The trend in chemical reactivity and stability of the studied compounds was observed to show increasing stability and decreasing reactivity and this was obtained from orbital energies. The effect of bromine and chlorine atoms, instead of fluorine atoms, is also noted. Surface analysis on the covalent bond was attained by ELF and LOL analysis. Biological activities were predicted using molecular docking studies. Docking results were analyzed with standard drugs, 5-fluorouracil/piperine. Antitumor activity of hydrazine derivatives was found to be higher than reference ones. Molecular dynamics (MD) simulation was performed for 100 ns to validate the stability behavior of hydrazine derivatives with the dual specificity threonine tyrosine kinase (TTK) protein. RMSD, RMSF, Rg, SASA, and intermolecular analysis of DFH, TMH, and BPH with threonine tyrosine kinase forms stable ligand-protein interactions. The molecular and predictive biological properties of three pharmaceutically active hydrazine derivatives which can be helpful to researchers in future experimental validation through in vitro and in vivo studies.

Intercellular adhesion molecule-1 is a surrogate biomarker for subclinical atherosclerosis in Type 2 diabetes mellitus.

Aim: We aimed to investigate biomarkers of inflammation, oxidative stress as surrogate markers of subclinical atherosclerosis in patients with Type 2 diabetes mellitus (T2DM). Materials & methods: Subjects were grouped based on carotid intima media thickness (CIMT). Group 1: healthy controls (CIMT <0.57 mm); Group 2: T2DM without subclinical atherosclerosis (CIMT <0.57 mm); Group 3: T2DM with subclinical atherosclerosis (CIMT ≥0.57 mm). Results: Significantly higher MDA, Hs-CRP, Ox-LDL, PTX-3, IL-6, ICAM-1 and lower FRAP, IL-10 levels in T2DM groups compared with controls (p = 0.001). Changes were more significant in Group 3 compared with Group 2. ICAM-1 had the highest sensitivity and specificity at a cut-off value of >40.34 ng/ml compared with Ox-LDL and PTX-3 (p < 0.001). Conclusion: ICAM can be considered as an alternate surrogate biomarker of CIMT.

F-18 Fluorodeoxyglucose Positron Emission Tomography Computed Tomography Findings in an Interesting Case of Primary Cauda Equina Lymphoma with Literature Review.

Primary lymphomatous involvement of spinal cord, nerve roots, and cauda equina is a rare entity and comprises only 0.1% of extra-nodal lymphoma spectrum. Here, we present a case of non-Hodgkin lymphoma involving cauda equina, initially suspected as ependymoma on magnetic resonance imaging that was later confirmed on nerve root biopsy as high B cell non-Hodgkin's lymphoma of L1-S1 nerve roots. F-18 fluorodeoxyglucose positron emission tomography-computed tomography was performed for staging workup which showed abnormal metabolic activity within the spinal canal from D10-S2 with no evidence of distant organ involvement.

The Basic Helix-Loop-Helix Gene Nato3 Drives Expression of Dopaminergic Neuron Transcription Factors in Neural Progenitors.

The floor plate of the developing midbrain gives rise to dopaminergic (DA) neurons, an important class of cells involved in Parkinson's disease (PD). Neural progenitors of the midbrain floor plate utilize key genes in transcriptional networks to drive dopamine neurogenesis. Identifying factors that promote dopaminergic neuron transcriptional networks can provide insight into strategies for therapies in PD. Using the chick embryo, we developed a quantitative PCR (qPCR) based method to assess the potential of a candidate factor to drive DA neuron gene expression, including the basic helix-loop-helix transcription factor Nato3 (Ferd3l). We then showed that overexpression of Nato3 in the developing chick mesencephalon produces a regionally dependent increase in genes associated with the DA neurogenesis, (such as Foxa2, Lmx1b and Shh) as well as DA neuron genes Nurr1 (an immature DA neuron marker) and mRNA expression of tyrosine hydroxylase (TH, a mature DA neuron marker). Interestingly, our data also showed that Nato3 is a potent regulator of Lmx1b by its broad induction of Lmx1b expression in neural progenitors of multiple regions of the CNS, including the midbrain and spinal cord. These data introduce a new, in vivo approach to identifying a gene that can drive DA transcriptional networks and provide the new insight that Nato3 can drive expression of key DA neuron genes, including Lmx1b, in neural progenitors.

Cephalic Arch Stenosis: Location of Stenosis in Indian Hemodialysis Patients.

The cephalic vein is formed over the "anatomical snuff box" and joins the axillary vein just below the clavicular level. The definition of cephalic arch is varied. In the radiology literature, it is defined as the central perpendicular portion of the cephalic vein as it traverses the deltopectoral groove and joins the axillary vein. The possible etiologies of cephalic arch stenosis are numerous. This study aimed to identify patients with cephalic arch stenosis and to discern the domain site of stenosis. This is a retrospective case series of patients who had an arteriovenous fistula with dysfunction of access and ipsilateral upper-limb edema. The clinical features of the access dysfunction were strong pulse due to increased pressure, weak thrill due to poor proximal flow, high static pressure, or decreased dialysis efficiency. All these 25 patients underwent computed tomography (CT) angiogram. The CT angiographic findings revealed cephalic arch stenosis and stenosis in 13 patients (52%). domain IV was slightly more affected than other domains of cephalic arch.