Cell suspension cultures of Trigonella foenum graecum L. (fenugreek) were initiated from the cotyledon portions of sterile germinated seeds and maintained on MS medium supplemented with 2,4-dichlorophenoxy acetic acid (2, 4-D) (1 mg/l), kinetin (0.1 mg/l) and sucrose (5%). The changes in cell mass and both trigonelline and 4- hydroxyisoleucine content were followed between days zero and 12. The linear increase in fresh weight was found to be parallel to both trigonelline and 4-hydroxyisoleucine production. Cell suspension cultures treated with 100 μM methyl jasmonate (MJ) for 24 hours showed a noticeable increase in the level of trigonelline and 4-hydroxyisoleucine. The marked improvement in the histological and electron microscopically pictures of pancreas of STZ-diabetic rats fed with extract of cells treated with MJ is coincided with more effective and significant hypoglycemic activity than that for seeds extract. The extract of cultured cells treated with MJ lowered blood glucose from 284 ± 7.4 to 123 ± 8.1 units and increased the insulin level from 4.42 ± 0.23 μU/ml to a high level 8.33 ± 0.41 μU/ml.

Two methyl esters of fatty acids, namely octadecanoic acid methyl ester (methyl stearate) (1) and hexadecanoic acid methyl ester (methyl palmitate) (2), in addition to four cinnamyl alcohol derivatives, sinapyl alcohol (3), coniferyl alcohol (4), p-coumaryl alcohol (5) and coniferyl alcohol 4-O-glucoside (coniferin) (6), were isolated from callus cultures of Wedelia prostrata. The structure of coniferin was established by spectroscopic and chemical methods, while the other compounds were identified by gas chromatography – mass spectrometry and thin layer chromatography in comparison with standards

Cardiac glycosides in shoot cultures of Cryptostegia grandiflora were identified when grown in modified MS medium. The change in shoot segments and cardiac glycosides content was followed between day zero and day 12 at 2-day intervals. The content of cardiac glycosides in leaves and shoot cultures of cryptostegia grandiflora was monitored by HPLC. Two major compounds were detected and isolated from shoot cultures extract, named oleandrigenin 3-O--glucopyranosyl-(14)--cymaropyranosyl-(14)--digitoxopyranoside (cryptostigmin I) and oleandrigenin 3-O--glucopyranosyl-(14)--rhamnopyranoside (cryptostigmin II). The structures of the isolated compounds were verified by means of MS and NMR spectral analysis as well as by comparison with authentic samples. The leaves and shoot cultures were analyzed for their cardiac glycosides content. The shoot cultures inoculated into MS-based culture media supplemented with 0.1 mg L-1 BA, 30 g L-1 sucrose, 0.1 g L-1 myo-inositol and 0.1 g L-1 ascorbic acid were found to contain a quantity of cardiac glycosides that was about four fold the cardiac glycosides content of leaves extract

Shoot tips of the germinated seeds of Astragalus sieberi DC. were cultured on MS-medium supplemented with 0.1 mg L-1 each of naphthalene acetic acid (NAA) and benzyl adenine (BA) for establishment of shoot cultures. The effect of different concentrations of growth regulators on saponin content was studied and optimized. Saponin content was monitored by HPLC analysis. The most appropriate growth regulator with which to produce the highest content of saponins in shoot cultures was 0.5 mg L-1 each of NAA and BA. The isolated cycloastragenol-3-O-glucoside was identified by spectral analysis and compared with an authentic sample

The finding that oxygenase-catalyzed protein hydroxylation regulates animal transcription raises questions as to whether the translation machinery and prokaryotic proteins are analogously modified. Escherichia coli ycfD is a growth-regulating 2-oxoglutarate oxygenase catalyzing arginyl hydroxylation of the ribosomal protein Rpl16. Human ycfD homologs, Myc-induced nuclear antigen (MINA53) and NO66, are also linked to growth and catalyze histidyl hydroxylation of Rpl27a and Rpl8, respectively. This work reveals new therapeutic possibilities via oxygenase inhibition and by targeting modified over unmodified ribosomes.

Polymeric nanoparticles-based therapeutics show great promise in the treatment of a wide range of diseases, due to the flexibility in which their structures can be modified, with intricate definition over their compositions, structures and properties. Advances in polymerization chemistries and the application of reactive, efficient and orthogonal chemical modification reactions have enabled the engineering of multifunctional polymeric nanoparticles with precise control over the architectures of the individual polymer components, to direct their assembly and subsequent transformations into nanoparticles of selective overall shapes, sizes, internal morphologies, external surface charges and functionalizations. In addition, incorporation of certain functionalities can modulate the responsiveness of these nanostructures to specific stimuli through the use of remote activation. Furthermore, they can be equipped with smart components to allow their delivery beyond certain biological barriers, such as skin, mucus, blood, extracellular matrix, cellular and subcellular organelles. This tutorial review highlights the importance of well-defined chemistries, with detailed ties to specific biological hurdles and opportunities, in the design of nanostructures for various biomedical delivery applications.

Polymeric nanoparticles are promising delivery platforms for various biomedical applications. One of the main challenges toward the development of therapeutic nanoparticles is the premature disassembly and release of the encapsulated drug. Among the different strategies to enhance the kinetic stability of polymeric nanoparticles, shell- and core-crosslinking have been shown to provide robust character, while creating a suitable environment for encapsulation of a wide range of therapeutics, including hydrophilic, hydrophobic, metallic, and small and large biomolecules, with gating of their release as well. The versatility of shell- and core-crosslinked nanoparticles is driven from the ease by which the structures of the shell- and core-forming polymers and crosslinkers can be modified. In addition, postmodification with cell-recognition moieties, grafting of antibiofouling polymers, or chemical degradation of the core to yield nanocages allow the use of these robust nanostructures as ‘‘smart’’ nanocarriers. The building principles of these multifunctional nanoparticles borrow analogy from the synthesis, supramolecular assembly, stabilization, and dynamic activity of the naturally driven biological nanoparticles such as proteins, lipoproteins, and viruses. In this review, the chemistry involved during the buildup from small molecules to polymers to covalently stabilized nanoscopic objects is detailed, with contrast of the strategies of the supramolecular assembly of polymer building blocks followed by intramicellar stabilization into shell-, core-, or core-shell-crosslinked knedel-like nanoparticles versus polymerization of polymers into nanoscopic molecular brushes followed by further intramolecular covalent stabilization events. The rational design of shell-crosslinked knedel-like nanoparticles is then elaborated for therapeutic packaging and delivery, with emphasis on the polymer chemistry aspects to accomplish the synthesis of such nanoparticulate systems.

Cationic shell crosslinked knedel-like nanoparticles (cSCKs) have emerged as a highly efficient transfection agent for nucleic acids delivery. In this study, a new class of cSCKs with tunable buffering capacities has been developed by altering the amounts of histamines and primary amines incorporated into their crosslinked shell regions. The effect of histamine content of these nanoparticles with a hydrodynamic diameter of ca. 20 nm, on the siRNA-binding affinity, cytotoxicity, immunogenicity, and transfection efficiency was investigated. The modification of cSCKs with histamine was found to reduce the siRNA-binding affinity and cellular binding. On the other hand, it significantly reduced the toxicity and immunogenicity of the nanoparticles with subsequent increase in the transfection efficiency. In addition, escape from endosomes was facilitated by having two species of low and high pKas (i.e. histamine and primary amine groups, respectively), as demonstrated by the potentiometric titration experiments and the effect of bafilomycin A1, an inhibitor of the endosomal acidification, on the transfection efficiency of cSCKs. Histamine modification of 15 mol% was a threshold, above which cSCKs with higher histamine content completely lost the ability to bind siRNA and to transfect cells. This study highlights the potential of histamine incorporation to augment the gene silencing activity of cationic nanoparticles, reduce their toxicity, and increase their biocompatibility, which is of particular importance in the design of nucleic acids delivery vectors.