Predicting ion concentration polarization and analyte stacking/focusing at nanofluidic interfaces

We report on the investigation of electropreconcentration phenomena in micro-/nanofluidic devices integrating 100 μm long nanochannels using 2D COMSOL simulations based on the coupled Poisson–Nernst–Planck and Navier–Stokes system of equations. Our numerical model is used to demonstrate the influence of key governing parameters such as electrolyte concentration, surface charge density, and applied axial electric field on ion concentration polarization (ICP) dynamics in our system. Under sufficiently extreme surface-charge-governed transport conditions, ICP propagation is shown to enable various transient and stationary stacking and counter-flow gradient focusing mechanisms of anionic analytes. We resolve these spatiotemporal dynamics of analytes and electrolyte ICP over disparate time and length scales, and confirm previous findings that the greatest enhancement is observed when a system is tuned for analyte focusing at the charge, excluding microchannel, nanochannel electrical double layer (EDL) interface. Moreover, we demonstrate that such tuning can readily be achieved by including additional nanochannels oriented parallel to the electric field between two microchannels, effectively increasing the overall perm-selectivity and leading to enhanced focusing at the EDL interfaces. This approach shows promise in providing added control over the extent of ICP in electrokinetic systems, particularly under circumstances in which relatively weak ICP effects are observed using only a single channel.     

A Narrative Review on the Phytochemistry,Pharmacology and Therapeutic Potentials of Clinacanthus nutans (Burm. f.) Lindau Leaves as an Alternative Source of Future Medicine

The application of natural products and supplements has expanded tremendously over the past few decades. Clinacanthus nutans (C. nutans), which is affiliated to the Acanthaceae family, has recently caught the interest of researchers from the countries of subtropical Asia due to its medicinal uses in alternative treatment for skin infection conditions due to insect bites, microorganism infections and cancer, as well as for health well-being. A number of bioactive compounds from this plant’s extract, namely phenolic compounds, sulphur containing compounds, sulphur containing glycosides compounds, terpens-tripenoids, terpens-phytosterols and chlorophyll-related compounds possess high antioxidant activities. This literature search yielded about one hundred articles which were then further documented, including the valuable data and findings obtained from all accessible electronic searches and library databases. The promising pharmacological activities from C. nutans leaves extract, including antioxidant, anti-cancer, anti-viral, anti-bacterial, anti-fungal, anti-venom, analgesic and anti-nociceptive properties were meticulously dissected. Moreover, the authors also discuss a few of the pharmacological aspect of C. nutans leaves extracts against anti-hyperlipidemia, vasorelaxation and renoprotective activities, which are seldom available from the previously discussed review papers. From the aspect of toxicological studies, controversial findings have been reported in both in-vitro and in-vivo experiments. Thus, further investigations on their phytochemical compounds and their mode of action showing pharmacological activities are required to fully grasp both traditional usage and their suitability for future drugs development. Data related to therapeutic activity and the constituents of C. nutans leaves were searched by using the search engines Google scholar, PubMed, Scopus and Science Direct, and accepting literature reported between 2010 to present. On the whole, this review paper compiles all the available contemporary data from this subtropical herb on its phytochemistry and pharmacological activities with a view towards garnering further interest in exploring its use in cardiovascular and renal diseases.     

Synthesis and Antimicrobial Activity of Some Novel 7-Chloro-4-aminoquinoline Derivatives

Russian Journal of General Chemistry - A number of novel 7-chloro-4-aminoquinoline derivatives have been efficiently synthesized by nucleophilic aromatic substitution reaction of...     

Human Group IIA Phospholipase A2—Three Decades on from Its Discovery

Phospholipase A₂ (PLA₂) enzymes were first recognized as an enzyme activity class in 1961. The secreted (sPLA₂) enzymes were the first of the five major classes of human PLA₂s to be identified and now number nine catalytically-active structurally homologous proteins. The best-studied of these, group IIA sPLA₂, has a clear role in the physiological response to infection and minor injury and acts as an amplifier of pathological inflammation. The enzyme has been a target for anti-inflammatory drug development in multiple disorders where chronic inflammation is a driver of pathology since its cloning in 1989. Despite intensive effort, no clinically approved medicines targeting the enzyme activity have yet been developed. This review catalogues the major discoveries in the human group IIA sPLA₂ field, focusing on features of enzyme function that may explain this lack of success and discusses future research that may assist in realizing the potential benefit of targeting this enzyme. Functionally-selective inhibitors together with isoform-selective inhibitors are necessary to limit the apparent toxicity of previous drugs. There is also a need to define the relevance of the catalytic function of hGIIA to human inflammatory pathology relative to its recently-discovered catalysis-independent function.     

The Nephroprotective Effect of Zizyphus lotus L. (Desf.) Fruits in a Gentamicin-Induced Acute Kidney Injury Model in Rats: A Biochemical and Histopathological Investigation

Zizyphus lotus L. (Desf.) (Z. lotus) is a medicinal plant largely distributed all over the Mediterranean basin and is traditionally used by Moroccan people to treat many illnesses, including kidney failure. The nephrotoxicity of gentamicin (GM) has been well documented in humans and animals, although the preventive strategies against it remain to be studied. In this investigation, we explore whether the extract of Zizyphus lotus L. (Desf.) Fruit (ZLF) exhibits a protective effect against renal damage produced by GM. Indeed, twenty-four Wistar rats were separated into four equal groups of six each (♂/♀ = 1). The control group was treated orally with distilled water (10 mL/kg); the GM treated group received distilled water (10 mL/kg) and an intraperitoneal injection of GM (80 mg/kg) 3 h after; and the treated groups received ZLF extract orally at the doses 200 or 400 mg/kg and injected intraperitoneally with the GM. All treatments were given daily for 14 days. At the end of the experiment, the biochemical parameters and the histological observation related the kidney function was explored. ZLF treatment has significantly attenuated the nephrotoxicity induced by the GM. This effect was indicated by its capacity to decrease significantly the serum creatinine, uric acid, urea, alkaline phosphatase, gamma-glutamyl-transpeptidase, albumin, calcium, sodium amounts, water intake, urinary volume, and relative kidney weight. In addition, this effect was also shown by the increase in the creatinine clearance, urinary creatinine, uric acid, and urea levels, weight gain, compared to the rats treated only with the GM. The hemostasis of oxidants/antioxidants has been significantly improved with the treatment of ZLF extract, which was shown by a significant reduction in malondialdehydes levels. Histopathological analysis of renal tissue was correlated with biochemical observation. Chemical analysis by HPLC-DAD showed that the aqueous extract of ZLF is rich in phenolic compounds such as 3-hydroxycinnamic acid, catechin, ferulic acid, gallic acid, hydroxytyrosol, naringenin, p- coumaric Acid, quercetin, rutin, and vanillic acid. In conclusion, ZLF extract improved the nephrotoxicity induced by GM, through the improvement of the biochemical and histological parameters and thus validates its ethnomedicinal use.     

In Vitro Inhibitory Analysis of Rationally Designed siRNAs against MERS-CoV Replication in Huh7 Cells

MERS-CoV was identified for the first time in Jeddah, Saudi Arabia in 2012 in a hospitalized patient. This virus subsequently spread to 27 countries with a total of 939 deaths and 2586 confirmed cases and now has become a serious concern globally. Camels are well known for the transmission of the virus to the human population. In this report, we have discussed the prediction, designing, and evaluation of potential siRNA targeting the ORF1ab gene for the inhibition of MERS-CoV replication. The online software, siDirect 2.0 was used to predict and design the siRNAs, their secondary structure and their target accessibility. ORF1ab gene folding was performed by RNAxs and RNAfold software. A total of twenty-one siRNAs were selected from 462 siRNAs according to their scoring and specificity. siRNAs were evaluated in vitro for their cytotoxicity and antiviral efficacy in Huh7 cell line. No significant cytotoxicity was observed for all siRNAs in Huh7 cells. The in vitro study showed the inhibition of viral replication by three siRNAs. The data generated in this study provide preliminary and encouraging information to evaluate the siRNAs separately as well as in combination against MERS-CoV replication in other cell lines. The prediction of siRNAs using online software resulted in the filtration and selection of potential siRNAs with high accuracy and strength. This computational approach resulted in three effective siRNAs that can be taken further to in vivo animal studies and can be used to develop safe and effective antiviral therapies for other prevalent disease-causing viruses.     

Isolation and antiproliferative activity of triterpenoids and fatty acids from the leaves and stem of Turraea vogelii Hook. f. ex benth

Chloroform extract from the leaves of Turraea vogelii Hook f. ex Benth demonstrated cytotoxic activity against a chronic myelogenous leukemia cell, K-562 with IC₅₀ of 14.27 μg/mL, while chloroform, ethyl acetate and methanol extracts from the stem of the plant inhibited K-562 cells growth with IC₅₀ of 19.50, 24.10 and 85.40 μg/mL respectively. Bioactive chloroform extract of Turraea vogelii leaves affords two triterpenoids: oleana-12,15,20-trien-3β-ol (1), and oleana-11,13-dien-3β,16α,28-triol (2), with six fatty esters, ethyl hexaeicos-5-enoate (3), 3-hydroxy-1,2,3-propanetriyltris(tetadecanoate) (4), 1,2,3-propanetriyl(7Z,7′Z,7′′Z)tris(-7-hexadecenoate) (5), 1,2,3-propanetriyl(5Z,5′Z,5′′Z)tris(-5-hexadecenoate) (6), 1,2,3-propanetriyltris(octadecanoate) (7), and 2β-hydroxymethyl tetraeicosanoate (8). Tetradecane (9), four fatty acids: hexadecanoic acid (10), tetradecanoic acid (11), (Z)-9-eicosenoic acid (12), and ethyl tetradec-7-enoate (13) were isolated from chloroform extract of Turraea vogelii stem. 1,2,3-propanetriyltris(heptadecanoate) (14), (Z)-9-octadecenoic acid (15) and (Z)-7-tetradecenoic acid (16) were isolated from ethyl acetate extract while (Z)-5-pentadecenoic acid (17) was obtained from methanol extract of the plant stem. Compounds 1, 2, 5, 6, 11, 12, 15, 16 and 17 exhibited pronounced antiproliferative activity against K-562 cell lines.     

Polyphenolic profiling of Ipomoea carnea Jacq. by HPLC-DAD and its implications in oxidative stress and cancer

Ipomoea carnea Jacq. is an important folklore medicinal plant, assessed for its underexplored biological potential. Antioxidant, cytotoxic, antiproliferative and polyphenolic profile of whole plant was evaluated using various techniques. Maximum extract recovery (29% w/w), phenolic [13.54 ± 0.27 μg GAE/mg dry weight (DW)] and flavonoid (2.11 ± 0.10 μg QE /mg DW) content were recorded in methanol-distilled water (1:1) flower extract. HPLC-DAD analysis quantified substantial amount of six different polyphenols ranging from 0.081 to 37.95 μg/mg extract. Maximum total antioxidant and reducing potential were documented in methanol-distilled water and acetone-distilled water flower extracts (42.62 ± 0.47 and 24.38 ± 0.39 μg AAE/mg DW) respectively. Ethanol-chloroform root extract manifested highest free radical scavenging (IC₅₀ of 61.22 μg/mL) while 94.64% of the extracts showed cytotoxicity against brine shrimps. Ethanol leaf extract exhibited remarkable activity against THP-1 cell line (IC₅₀ = 8 ± 0.05 μg/mL) and protein kinases (31 mm phenotype bald zone).     

Nylon Intermediates from Bio‐Based Levulinic Acid

Use of ZrO₂/SiO₂ as a solid acid catalyst in the ring‐opening of biobased γ‐valerolactone with methanol in the gas phase leads to mixtures of methyl 2‐, 3‐, and 4‐pentenoate (MP) in over 95 % selectivity, containing a surprising 81 % of M4P. This process allows the application of a selective hydroformylation to this mixture to convert M4P into methyl 5‐formyl‐valerate (M5FV) with 90 % selectivity. The other isomers remain unreacted. Reductive amination of M5FV and ring‐closure to ?‐caprolactam in excellent yield had been reported before. The remaining mixture of 2‐ and 3‐MP was subjected to an isomerising methoxycarbonylation to dimethyl adipate in 91 % yield.     

vic‐Tricarbonyl Compounds of Quinolines: Analogues of Ninhydrin: A Short Review

Derivatives of ninhydrin are extensively used in the field of forensic sciences as important latent fingerprint reagents. Many works have been performed upon their synthesis and reactivity, but there are many spaces to work on the compounds of quinoline‐2,3,4(1H)‐triones—analogues of ninhydrin, in both dimensions: synthesis and reactivity, and according to the best of our knowledge, not a single detailed or short compiled article has been published for these compounds. This review briefly summarizes the chemistry of quinoline‐2,3,4(1H)‐triones.