An Optical Chemical Sensor Based on Swellable Dicarboxylate Functionalized Polymer Microspheres for pH Copper and Calcium Determination

An optical chemical sensor based on polymer swelling and shrinking has been studied by way of optical transmission. Polyvinylbenzyl chloride cross-linked with divinylbenzene and derivatized as the dicarboxylate was dispersed as microspheres in a hydrogel membrane. The absorbance was measured vs. the wavelength upon exposing the modified membrane to solutions of varying pH (3.0–9.0). At low pH (3.0), the absorbance had the highest value (1.34), while the absorbance decreased significantly (1.10) when the pH was increased to 9.0, indicating polymer swelling.The modified membrane was also used for sensing metal ions, in particular calcium and copper. Complex formation with the dicarboxylate functionality caused the polymer to shrink. This resulted in an increase in absorbance for a concentration ranging from 1.0×10^–3 to 4.0×10^–3M.     

Bioassay Guided Isolation and Identification of a Cytotoxic Compound from Azadirachta indica Leaves

This study aimed to investigate the structural features of the isolated flavonol glycoside, which might behave as a cytotoxic compound. The hexane, chloroform, ethyl acetate, and aqueous fractions of an 80% methanol solution of Neem (Azadirachta indica) (Family: Meliaceae) leaves were subjected to a cytotoxicity bioassay against brine shrimp, Artemia salina. The ethyl acetate fraction exhibited the highest cytotoxic effect, supported by the lowest lethal concentration, a LC₅₀ value of 1.35±0.40 ppm. A compound, Quercetin 3‐O‐β‐D‐glucopyranoside, was isolated from the most toxic fraction of the ethyl acetate via preparative liquid chromatography and then identified via ultraviolet‐visible (UV‐Vis), infrared (IR), mass spectrum (MS) and nuclear magnetic resonance (NMR) analyses. The compound was further confirmed by physical state, color, solubility, and melting point determination. The cytotoxic results suggest that the leaf ethyl acetate fraction consists of toxic compounds, which point towards the isolation of Quercetin 3‐O‐β‐D‐glucopyranoside.     

Optical beam instabilities in nonlinear nanosuspensions

We investigate the modulation instability of plane waves and the transverse instabilities of soliton stripe beams propagating in nonlinear nanosuspensions. We show that in these systems the process of modulational instability depends on the input beam conditions. On the other hand, the transverse instability of soliton stripes can exhibit new features as a result of 1D collapse caused by the exponential nonlinearity.     

The Renin-Angiotensin System: A Key Role in SARS-CoV-2-Induced COVID-19

The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of coronavirus disease 2019 (COVID-19), was first identified in Eastern Asia (Wuhan, China) in December 2019. The virus then spread to Europe and across all continents where it has led to higher mortality and morbidity, and was declared as a pandemic by the World Health Organization (WHO) in March 2020. Recently, different vaccines have been produced and seem to be more or less effective in protecting from COVID-19. The renin–angiotensin system (RAS), an essential enzymatic cascade involved in maintaining blood pressure and electrolyte balance, is involved in the pathogenicity of COVID-19, since the angiotensin-converting enzyme II (ACE2) acts as the cellular receptor for SARS-CoV-2 in many human tissues and organs. In fact, the viral entrance promotes a downregulation of ACE2 followed by RAS balance dysregulation and an overactivation of the angiotensin II (Ang II)–angiotensin II type I receptor (AT1R) axis, which is characterized by a strong vasoconstriction and the induction of the profibrotic, proapoptotic and proinflammatory signalizations in the lungs and other organs. This mechanism features a massive cytokine storm, hypercoagulation, an acute respiratory distress syndrome (ARDS) and subsequent multiple organ damage. While all individuals are vulnerable to SARS-CoV-2, the disease outcome and severity differ among people and countries and depend on a dual interaction between the virus and the affected host. Many studies have already pointed out the importance of host genetic polymorphisms (especially in the RAS) as well as other related factors such age, gender, lifestyle and habits and underlying pathologies or comorbidities (diabetes and cardiovascular diseases) that could render individuals at higher risk of infection and pathogenicity. In this review, we explore the correlation between all these risk factors as well as how and why they could account for severe post-COVID-19 complications.     

Nifuroxazide Mitigates Angiogenesis in Ehlrich’s Solid Carcinoma: Molecular Docking,Bioinformatic and Experimental Studies on Inhibition of Il-6/Jak2/Stat3 Signaling

Nifuroxazide is an antidiarrheal medication that has promising anticancer activity against diverse types of tumors. The present study tested the anticancer activity of nifuroxazide against Ehrlich’s mammary carcinoma grown in vivo. Furthermore, we investigated the effect of nifuroxazide on IL-6/jak2/STAT3 signaling and the possible impact on tumor angiogenesis. The biological study was supported by molecular docking and bioinformatic predictions for the possible effect of nifuroxazide on this signaling pathway. Female albino mice were injected with Ehrlich carcinoma cells to produce Ehrlich’s solid tumors (ESTs). The experimental groups were as follows: EST control, EST + nifuroxazide (5 mg/kg), and EST + nifuroxazide (10 mg/kg). Nifuroxazide was found to reduce tumor masses (730.83 ± 73.19 and 381.42 ± 109.69 mg vs. 1099.5 ± 310.83) and lessen tumor pathologies. Furthermore, nifuroxazide downregulated IL-6, TNF-α, NFk-β, angiostatin, and Jak2 proteins, and it also reduced tumoral VEGF, as indicated by ELISA and immunohistochemical analysis. Furthermore, nifuroxazide dose-dependently downregulated STAT3 phosphorylation (60% and 30% reductions, respectively). Collectively, the current experiment shed light on the antitumor activity of nifuroxazide against mammary solid carcinoma grown in vivo. The antitumor activity was at least partly mediated by inhibition of IL-6/Jak2/STAT3 signaling that affected angiogenesis (low VEGF and high angiostatin) in the EST. Therefore, nifuroxazide might be a promising antitumor medication if appropriate human studies will be conducted.     

Interfacial properties of diblock copolymers at penetrable interfaces: Density profile,stretching, and interfacial tension

The interfacial properties of diblock (AB) copolymers near an interface between two solvents are studied by using the exact Green's function of a Gaussian copolymer chain at an attractive penetrable interface. We have studied the mean‐square end‐to‐end distance of the copolymer, 〈R²(z)〉, as a function of the distance of the joint point of the copolymer to the interface, z, the segment density distribution ρ(z), and the reduction of the interfacial tension Δγ_c due to the presence of the diblock copolymer. The density profile and the stretching of the copolymer chain are in agreement with both experimental results and simulations. The reduction in the interfacial tension is found to decrease with the increase in the degree of polymerization of the copolymer chain.     

Deprotometalation-Iodolysis and Direct Iodination of 1-Arylated 7-Azaindoles: Reactivity Studies and Molecule Properties

Five protocols were first compared for the copper-catalyzed C-N bond formation between 7-azaindole and aryl/heteroaryl iodides/bromides. The 1-arylated 7-azaindoles thus obtained were subjected to deprotometalation-iodolysis sequences using lithium 2,2,6,6-tetramethylpiperidide as the base and the corresponding zinc diamide as an in situ trap. The reactivity of the substrate was discussed in light of the calculated atomic charges and the pK_a values. The behavior of the 1-arylated 7-azaindoles in direct iodination was then studied, and the results explained by considering the HOMO orbital coefficients and the atomic charges. Finally, some of the iodides generated, generally original, were involved in the N-arylation of indole. While crystallographic data were collected for fifteen of the synthesized compounds, biological properties (antimicrobial, antifungal and antioxidant activity) were evaluated for others.     

Angiotensin II Type I Receptor (AT1R): The Gate towards COVID-19-Associated Diseases

The binding of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein to its cellular receptor, the angiotensin-converting enzyme 2 (ACE2), causes its downregulation, which subsequently leads to the dysregulation of the renin–angiotensin system (RAS) in favor of the ACE–angiotensin II (Ang II)–angiotensin II type I receptor (AT1R) axis. AT1R has a major role in RAS by being involved in several physiological events including blood pressure control and electrolyte balance. Following SARS-CoV-2 infection, pathogenic episodes generated by the vasoconstriction, proinflammatory, profibrotic, and prooxidative consequences of the Ang II–AT1R axis activation are accompanied by a hyperinflammatory state (cytokine storm) and an acute respiratory distress syndrome (ARDS). AT1R, a member of the G protein-coupled receptor (GPCR) family, modulates Ang II deleterious effects through the activation of multiple downstream signaling pathways, among which are MAP kinases (ERK 1/2, JNK, p38MAPK), receptor tyrosine kinases (PDGF, EGFR, insulin receptor), and nonreceptor tyrosine kinases (Src, JAK/STAT, focal adhesion kinase (FAK)), and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. COVID-19 is well known for generating respiratory symptoms, but because ACE2 is expressed in various body tissues, several extrapulmonary pathologies are also manifested, including neurologic disorders, vasculature and myocardial complications, kidney injury, gastrointestinal symptoms, hepatic injury, hyperglycemia, and dermatologic complications. Therefore, the development of drugs based on RAS blockers, such as angiotensin II receptor blockers (ARBs), that inhibit the damaging axis of the RAS cascade may become one of the most promising approaches for the treatment of COVID-19 in the near future. We herein review the general features of AT1R, with a special focus on the receptor-mediated activation of the different downstream signaling pathways leading to specific cellular responses. In addition, we provide the latest insights into the roles of AT1R in COVID-19 outcomes in different systems of the human body, as well as the role of ARBs as tentative pharmacological agents to treat COVID-19.     

Capillary electrochromatography with monolithic silica columns. V. Study of the electrochromatographic behaviors of polar compounds on monolithic silica having surface bound cyano functionalities

In this report, a novel polar monolithic capillary column is described for normal phase CEC (NP-CEC) of representative polar compounds including mono- and oligosaccharides, peptides, and basic drugs. The polar monolithic column, which was described in detail in the preceding paper, consisted of silica-based monolith bonded with 1H-imidazole-4,5-dicarbonitrile (IDCN) and is denoted as 2CN-OH-Monolith. Various retention parameters for neutral polar solutes (e.g., mono- and oligosaccharides) and charged polar solutes (e.g., peptides and basic drugs) were evaluated over a wide-range of elution conditions. These retention parameters yielded quantitative assessment for the polar interactions between the model solutes and the stationary phase under investigation as well as the effect of electromigration of charged solutes on their overall migration in NP-CEC. Furthermore, this investigation demonstrated that despite the possibility of achieving isocratic separation in NP-CEC for widely differing polar species, multistep-gradient elution in NP-CEC is preferred to bring about the rapid separation of a large number of polar species in a single run.