Cell detection and counting through cell lysate impedance spectroscopy in microfluidic devices

Cell-based microfluidic devices have attracted interest for a wide range of applications. While optical cell counting and flow cytometry-type devices have been reported extensively, sensitive and efficient non-optical methods to detect and quantify cells attached over large surface areas within microdevices are generally lacking. We describe an electrical method for counting cells based on the measurement of changes in conductivity of the surrounding medium due to ions released from surface-immobilized cells within a microfluidic channel. Immobilized cells are lysed using a low conductivity, hypotonic media and the resulting change in impedance is measured using surface patterned electrodes to detect and quantify the number of cells. We found that the bulk solution conductance increases linearly with the number of isolated cells contributing to solution ion concentration. The method of cell lysate impedance spectroscopy is sensitive enough to detect 20 cells microL(-1), and offers a simple and efficient method for detecting and enumerating cells within microfluidic devices for many applications including measurement of CD4 cell counts in HIV patients in resource-limited settings. To our knowledge, this is the most sensitive approach using non-optical setups to enumerate immobilized cells. The microfluidic device, capable of isolating specific cell types from a complex bio-fluidic and quantifying cell number, can serve as a single use cartridge for a hand-held instrument to provide simple, fast and affordable cell counting in point-of-care settings.     

An electrolytic device for preparation of hydrogen and oxygen from water for isotopic analysis

An electrolytic device for decomposition of water has been developed which readily gives hydrogen and oxygen for isotopic measurement with a mass spectrometer. A 20-mul sample can be decomposed quantitatively in 10 min with good reproducibility. The results produced are comparable with those obtained by reduction with uranium.     

A review on <Superscript>90</Superscript>Y-labeled compounds and biomolecules

The field of therapeutic nuclear medicine is emerging rapidly as choice of treatment in oncology and other cellular malignancies. The growth of this branch of nuclear medicine is greatly facilitated by the introduction of a number of new radiopharmaceuticals and radionuclides. ⁹⁰Y-radiopharmaceuticals have confirmed their worth in medical and clinical areas in a very short span of time. The ⁹⁰Y is a radioisotope widely used for therapeutic purposes and considerable perfection has been made to understand the chemistry of ⁹⁰Y-labeled radiopharmaceuticals. The development of these radiopharmaceuticals can be made favorable by using appropriate buffer, incubation period, optimal pH, specific activity and reaction temperature. In this review, we have discussed the preparation of range of ⁹⁰Y transporting biological molecules such as antibodies radiolabeled peptides, antigens and microsphere with their clinical applications.     

Curcumin Attenuated Neurotoxicity in Sporadic Animal Model of Alzheimer’s Disease

Alzheimer’s disease (AD) is one of the most common neurodegenerative diseases leading to dementia. Despite research efforts, currently there are no effective pharmacotherapeutic options for the prevention and treatment of AD. Recently, numerous studies highlighted the beneficial effects of curcumin (CUR), a natural polyphenol, in the neuroprotection. Especially, its dual antioxidant and anti-inflammatory properties attracted the interest of researchers. In fact, besides its antioxidant and anti-inflammatory properties, this biomolecule is not degraded in the intestinal tract. Additionally, CUR is able to cross the blood–brain barrier and could therefore to be used to treat neurodegenerative pathologies associated with oxidative stress, inflammation and apoptosis. The present study aimed to assess the ability of CUR to induce neuronal protective and/or recovery effects on a rat model of neurotoxicity induced by aluminum chloride (AlCl₃), which mimics the sporadic form of Alzheimer’s disease. Our results showed that treatment with CUR enhances pro-oxidant levels, antioxidant enzymes activities and anti-inflammatory cytokine production and decreases apoptotic cells in AlCl₃-exposed hippocampus rats. Additionally, histopathological analysis of hippocampus revealed the potential of CUR in decreasing the hallmarks in the AlCl₃-induced AD. We also showed that CUR post-treatment significantly improved the behavioral, oxidative stress and inflammation in AlCl₃-exposed rats. Taken together, our data presented CUR as a nutraceutical potential through its protective effects that are more interesting than recovery ones in sporadic model of AD.     

Polyphenol Rich Ajuga bracteosa Transgenic Regenerants Display Better Pharmacological Potential

Ajuga bracteosa Wall. ex Benth. is an endangered medicinal herb traditionally used against different ailments. The present study aimed to create new insight into the fundamental mechanisms of genetic transformation and the biological activities of this plant. We transformed the A. bracteosa plant with rol genes of Agrobacterium rhizogenes and raised the regenerants from the hairy roots. These transgenic regenerants were screened for in vitro antioxidant activities, a range of in vivo assays, elemental analysis, polyphenol content, and different phytochemicals found through HPLC. Among 18 polyphenolic standards, kaempferol was most abundant in all transgenic lines. Furthermore, transgenic line 3 (ABRL3) showed maximum phenolics and flavonoids content among all tested plant extracts. ABRL3 also demonstrated the highest total antioxidant capacity (8.16 ± 1 μg AAE/mg), total reducing power, (6.60 ± 1.17 μg AAE/mg), DPPH activity (IC50 = 59.5 ± 0.8 μg/mL), hydroxyl ion scavenging (IC50 = 122.5 ± 0.90 μg/mL), and iron-chelating power (IC50 = 154.8 ± 2 μg/mL). Moreover, transformed plant extracts produced significant analgesic, anti-inflammatory, anticoagulant, and antidepressant activities in BALB/c mice models. In conclusion, transgenic regenerants of A. bracteosa pose better antioxidant and pharmacological properties under the effect of rol genes as compared to wild-type plants.     

Convergent synthesis of carbonic anhydrase inhibiting bi-heterocyclic benzamides: Structure–activity relationship and mechanistic explorations through enzyme inhibition,kinetics, and computational studies

By using a convergent methodology, a novel series of N-arylated 4-yl-benzamides containing a bi-heterocyclic thiazole–triazole core was synthesized, and the structures of these hybrid molecules, 9a–k , were corroborated through spectral analyses. The in vitro studies of these multifunctional molecules demonstrated their potent carbonic anhydrase inhibition relative to the standard used. The kinetics mechanism was exposed by Lineweaver–Burk plots, which revealed that 9j inhibited carbonic anhydrase non-competitively by forming an enzyme-inhibitor complex. The inhibition constants K_i calculated from Dixon plots for this compound was 1.2 μM. The computational study was also persuasive with the experimental results, and these molecules disclosed good results of all scoring functions and interactions, which suggested a good binding to carbonic anhydrase. So, it was predicted from the inferred results that these molecules might be considered as promising medicinal scaffolds for various diseases related to the uncontrolled production of this enzyme.     

Novel products from attempted michael addition to 1-methyl-1,2,5,6-tetrahydropyridine-4-carbonitrile

The reaction of some phenols with the title compound, in the presence of sodium, gives 2-(2-hydroxyaryl_piperidine derivatives. Geometrical isomers have been separated, which differ in having an equatorial (A) or axial (B) cyano group on the piperidine chair (the methyl and aryl groups are equatorial in both forms). The x-ray crystallographic structures of an example of each of A and B are reported and the proton NMR spectra are assigned.     

Carbon-13 substituent chemical shifts of 4-substituted bicyclo[2.2.2]oct-1-yl cyanides

The carbon-13 substituent chemical shifts of 4-substituted bicyclo[2.2.2]oct-1-yl cyanides are a linear function of the substituent inductive parameters.     

Structurally Simple Osmium(II) Polypyridyl Complexes as Photosensitizers for Photodynamic Therapy in the Near Infrared**

Five osmium(II) polypyridyl complexes of the general formula [Os(4,7-diphenyl-1,10-phenanthroline)₂ L ]²⁺ were synthesized as photosensitizers for photodynamic therapy by varying the nature of the ligand L . Thanks to the pronounced π-extended structure of the ligands and the heavy atom effect provided by the osmium center, these complexes exhibit a high absorption in the near-infrared (NIR) region (up to 740 nm), unlike related ruthenium complexes. This led to a promising phototoxicity in vitro against cancer cells cultured as 2D cell layers but also in multicellular tumor spheroids upon irradiation at 740 nm. The complex [Os(4,7-diphenyl-1,10-phenanthroline)₂(2,2′-bipyridine)]²⁺ was found to be the most efficient against various cancer cell lines, with high phototoxicity indexes. Experiments on CT26 tumor-bearing BALB/c mice also indicate that the Os^II complexes could significantly reduce tumor growth following 740 nm laser irradiation. The high phototoxicity in the biological window of this structurally simple complex makes it a promising photosensitizer for cancer treatment.