Mechanistic Insight into Oxidative Stress-Triggered Signaling Pathways and Type 2 Diabetes

Oxidative stress (OS) is a metabolic dysfunction mediated by the imbalance between the biochemical processes leading to elevated production of reactive oxygen species (ROS) and the antioxidant defense system of the body. It has a ubiquitous role in the development of numerous noncommunicable maladies including cardiovascular diseases, cancers, neurodegenerative diseases, aging and respiratory diseases. Diseases associated with metabolic dysfunction may be influenced by changes in the redox balance. Lately, there has been increasing awareness and evidence that diabetes mellitus (DM), particularly type 2 diabetes, is significantly modulated by oxidative stress. DM is a state of impaired metabolism characterized by hyperglycemia, resulting from defects in insulin secretion or action, or both. ROS such as hydrogen peroxide and the superoxide anion introduce chemical changes virtually in all cellular components, causing deleterious effects on the islets of β-cells, in turn affecting insulin production. Under hyperglycemic conditions, various signaling pathways such as nuclear factor-κβ (NF-κβ) and protein kinase C (PKC) are also activated by ROS. All of these can be linked to a hindrance in insulin signaling pathways, leading to insulin resistance. Hyperglycemia-induced oxidative stress plays a substantial role in complications including diabetic nephropathy. DM patients are more prone to microvascular as well as atherosclerotic macrovascular diseases. This systemic disease affects most countries around the world, owing to population explosion, aging, urbanization, obesity, lifestyle, etc. However, some modulators, with their free radical scavenging properties, can play a prospective role in overcoming the debilitating effects of OS. This review is a modest approach to summarizing the basics and interlinkages of oxidative stress, its modulators and diabetes mellitus. It may add to the understanding of and insight into the pathophysiology of diabetes and the crucial role of antioxidants to weaken the complications and morbidity resulting from this chronic disease.     

The integral mean diffusivity for particle-gas mass transfer calculations under thermal plasma conditions

Plasma Chemistry and Plasma Processing - A new integral mean diffusivity is proposed for the calculation of the mass transfer rate around a small particle immersed in a thermal plasma gas....     

Syntheses of New Unsymmetrical 2,5‐Disubstituted‐1,3,4‐oxadiazoles and 1,2,4‐Triazolo[3,4‐b]‐1,3,4‐thiadiazoles Bearing Thieno[2,3‐c]pyrazolo Moiety

New series of (thieno[2,3‐c]pyrazolo‐5‐yl)‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazoles 10a , 10b , 10c and (thieno[2,3‐c]pyrazol‐5‐yl)‐1,3,4‐oxadiazol‐3(2H)‐yl)ethanones 6a , 6b , 6c has been synthesized from thieno[2,3‐c]pyrazole‐5‐carbohydrazide 3 by multistep reaction sequence. (5‐Aryl‐1,3,4‐oxadiazol‐2‐yl)‐1H‐thieno[2,3‐c]pyrazoles 4a , 4b , 4c were also synthesized from thieno[2,3‐c]pyrazole‐5‐carbohydrazide 3 by cyclization with various aromatic carboxylic acids. The hydrazide 3 was obtained by reaction of thieno[2,3‐c]pyrazole‐5‐carboxylate 2 with hydrazine hydrate in good yield, and compound 2 was obtained by the reaction of 5‐chloro‐3‐methyl‐1‐phenyl‐1H‐pyrazole‐4‐carbaldehyde 1 and 2‐ethyl thioglycolate in presence of sodium alcoholate in good yield.     

New Synthesis and Reactions of Ethyl 5‐amino‐4‐cyano‐1‐phenyl‐1H‐pyrazole‐3‐carboxylate

Synthesis of ethyl 5‐amino‐4‐cyano‐1‐phenyl‐1H‐pyrazole‐3‐carboxylate 5 has been achieved via abnormal Beckmann rearrangement of o‐chloroaldehyde 1 . Reaction of o‐aminocarbonitrile 5 with concentrated H₂SO₄ furnished expected o‐aminocarboxamide pyrazole 6 . Key intermediates o‐aminocarbonitrile 5 and o‐aminocarboxamide 6 were successfully utilized for the synthesis of pyrazolopyrimidine derivatives. The replacement of Cl in o‐chlorocarbonitrile 3 with secondary amine furnished new synthon 13 , which was further used for the synthesis of polysubstituted heterocycles. The obtained new products were well characterized by IR, ¹H and ¹³C NMR, and mass spectra.     

Discovery of Elusive K4O6, a Compound Stabilized by Configurational Entropy of Polarons

Synthesis of elusive K₄O₆ has disclosed implications of crucial relevance for new solid materials discovery. K₄O₆ forms in equilibrium from K₂O₂ and KO₂, in an all‐solid state, endothermic reaction at elevated temperature, undergoing back reaction upon cooling to ambient conditions. This tells that the compound is stabilized by entropy alone. Analyzing possible entropic contributions reveals that the configurational entropy of “localized” electrons, i.e., of polaronic quasi‐particles, provides the essential contribution to the stabilization. We corroborate this assumption by measuring the relevant heats of transformation and tracking the origin of entropy of formation computationally. These findings challenge current experimental and computational approaches towards exploring chemical systems for new materials by searching the potential energy landscape: one would fail in detecting candidates that are crucially stabilized by the configurational entropy of localized polarons.     

Enantiomeric deoxycholic acid: total synthesis, characterization, and preliminary toxicity toward colon cancer cell lines

Deoxycholic acid (DCA) is an endogenous secondary bile acid implicated in numerous pathological conditions including colon cancer formation and progression and cholestatic liver disease. DCA involvement in these disease processes results partly from its ability to modulate signaling cascades within the cell, presumably through both direct receptor activation and general detergent mediated membrane changes. To further explore DCA induced changes in cell signaling, we completed a total synthesis of enantiomeric deoxycholic acid (ent-DCA) from achiral 2-methyl-1,3-cyclopentanedione. Using a modified method of the synthesis of ent-testosterone that proceeds through the (R)-(-)-Hajos-Parrish ketone, we have completed the successful synthesis of ent-DCA in 25 steps with a yield of 0.3% with all stereochemical assignments of the product confirmed by X-ray crystallography. Our studies toward this synthesis also uncovered the methodology for the development of a novel A,B-cis steroidal skeleton system containing a C3-C9 single bond as well as conditions to selectively ketalize the typically less reactive 12-carbonyl in poly-keto A,B-cis androgens. The critical micelle concentration (cmc) of ent-DCA, determined by a dye solubilization method, was identical to the cmc of natural DCA. Toxicity studies toward HT-29 and HCT-116 human colon cancer cell lines demonstrated that ent-DCA had similar effects on proliferation, yet showed a markedly decreased ability to induce apoptosis as compared to natural DCA.     

Knudsen effect on plasma-particle mass transfer. I. Formulation and application to self-diffusion

The Knudsen effect on mass transfer between a plasma gas and a small particle is investigated. A predictive model is developed by incorporating the Z-potential approach into the jump theory. The predictions of the model are explored through a case study. The results indicate that the Knudsen effect is significant and depends strongly on the particle size and the surface conditions. The plasma and the particle surface temperatures are also found to be determining factors. Under certain conditions, it is observed that the Knudsen effect can enhance the plasma-particle mass transfer, contrary to the predictions of the previous near-isothermal models.     

Enantioselective organocatalytic synthesis of the chiral chromenes by domino oxa-Michael-aldol reaction

The proline based chiral organocatalyst has been found to be an efficient catalyst for enantioselective domino oxa-Michael-aldol reaction. This catalytic system provided the synthesis of substituted 2-aryl-2H-chromenes-3-carbaldehyde in good to high yields (73%–97%) with excellent enantioselectivity (up to 97%) and reasonable reaction times. The atom economy, high yield and mild reaction conditions are some of the important features of this protocol.     

Merging Gradient-Based Methods to Improve Benchtop NMR Spectroscopy: A New Tool for Flow Reaction Optimization

Emerging low cost, compact NMR spectrometers that can be connected in-line to a flow reactor are suited to study reaction mixtures. The main limitation of such spectrometers arises from their lower magnetic field inducing a reduced sensitivity and a weaker spectral resolution. For enhancing the spectral resolution, the merging of Pure-Shift methods recognized for line narrowing with solvent elimination schemes was implemented in the context of mixtures containing protonated solvents. One more step was achieved to further enhance the resolution power on compact systems, thanks to multiple elimination schemes prior to Pure-Shift pulse sequence elements. For the first time, we were able to remove up to 6 protonated solvent signals simultaneously by dividing their intensity by 500 to 1700 with a concomitant spectral resolution enhancement for signals of interest from 9 to 12 as compared to the standard 1D ¹H. Then, the potential of this new approach was shown on the flow synthesis of a complex benzoxanthenone structure.     

Evaluation of Probiotic Characteristics of Siderophoregenic <Emphasis Type="Italic">Bacillus</Emphasis> spp. Isolated from Dairy Waste

Siderophoregenic Bacillus strain DET9 has been selectively isolated from dairy waste. It was evaluated for probiotic characteristics and susceptibility pattern against antibiotics. Its spores showed excellent tolerance to simulated gastrointestinal tract conditions and exhibited antimicrobial activity against organisms such as Escherichia coli, Micrococcus flavus, and Staphylococcus aureus. Its susceptibility to antibiotics reduces the prospect to donate resistance determinants if administered in the form of probiotic preparations. It was observed to produce ∼60 mg/l catecholate type of siderophore under iron stressed conditions, identified as a 2,3-dihydroxy benzoic acid by high-performance liquid chromatography, infrared spectroscopy, nuclear magnetic resonance, and mass spectral analysis. Partial 16S-rRNA gene sequencing analysis shows that the isolate exhibited homology with Bacillus thuringiensis and Bacillus weihenstephanensis, whereas biochemical characterization revealed its novelty. DET9 exhibited no mortality of fishes in a 60-day trial, when fishes (surfi tetra) were challenged up to 100 ppm cell concentration, with their daily diet.