A Comprehensive Review on Therapeutic Perspectives of Phytosterols in Insulin Resistance: A Mechanistic Approach

Natural products in the form of functional foods have become increasingly popular due to their protective effects against life-threatening diseases, low risk of adverse effects, affordability, and accessibility. Plant components such as phytosterol, in particular, have drawn a lot of press recently due to a link between their consumption and a modest incidence of global problems, such as Type 2 Diabetes mellitus (T2DM), cancer, and cardiovascular disease. In the management of diet-related metabolic diseases, such as T2DM and cardiovascular disorders, these plant-based functional foods and nutritional supplements have unquestionably led the market in terms of cost-effectiveness, therapeutic efficacy, and safety. Diabetes mellitus is a metabolic disorder categoriszed by high blood sugar and insulin resistance, which influence major metabolic organs, such as the liver, adipose tissue, and skeletal muscle. These chronic hyperglycemia fallouts result in decreased glucose consumption by body cells, increased fat mobilisation from fat storage cells, and protein depletion in human tissues, keeping the tissues in a state of crisis. In addition, functional foods such as phytosterols improve the body’s healing process from these crises by promoting a proper physiological metabolism and cellular activities. They are plant-derived steroid molecules having structure and function similar to cholesterol, which is found in vegetables, grains, nuts, olive oil, wood pulp, legumes, cereals, and leaves, and are abundant in nature, along with phytosterol derivatives. The most copious phytosterols seen in the human diet are sitosterol, stigmasterol, and campesterol, which can be found in free form, as fatty acid/cinnamic acid esters or as glycosides processed by pancreatic enzymes. Accumulating evidence reveals that phytosterols and diets enriched with them can control glucose and lipid metabolism, as well as insulin resistance. Despite this, few studies on the advantages of sterol control in diabetes care have been published. As a basis, the primary objective of this review is to convey extensive updated information on the possibility of managing diabetes and associated complications with sterol-rich foods in molecular aspects.     

Development and Validation of High-Throughput Bioanalytical Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) Method for the Quantification of Newly Synthesized Antitumor Carbonic Anhydrase Inhibitors in Human Plasma

In the present study, a sensitive and fully validated bioanalytical high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the quantitative determination of three newly synthesized carbonic anhydrases inhibitors (CAIs) with potential antitumor activity in human plasma. The analytes and the internal standard (IS) were extracted using 1.5 mL acetonitrile from only 450 µL aliquots of human plasma to achieve the desired protein precipitation. Chromatographic separations were achieved on Phenomenex Kinetex^® C₁₈ column (100 × 4.6 mm, 2.6 µm) using a binary gradient elution mode with a run time of less than 6 min. The mobile phase consisted of solvent (A): 0.1% formic acid in 50% methanol and solvent B: 0.1% formic acid in acetonitrile (30:70, v/v), pumped at a flow rate of 0.8 mL/min. Detection was employed using triple quadrupole tandem mass spectrometer (API 3500) equipped with an electrospray ionization (ESI) source in the positive ion mode. Multiple reaction monitoring (MRM) mode was selected for quantitation through monitoring the precursor-to-parent ion transition at m/z 291.9 → 173.0, m/z 396.9 → 225.1, m/z 388.9 → 217.0, and m/z 146.9 → 91.0 for AW-9a, WES-1, WES-2, and Coumarin (IS), respectively. Linearity was computed using the weighted least-squares linear regression method (1/x²) over a concentration range of 1–1000, 2.5–800, and 5–500 ng/mL for AW-9a, WES-1, and WES-2; respectively. The bioanalytical LC-MS/MS method was fully validated as per U.S. Food and Drug Administration (FDA) guidelines with all respect to linearity, accuracy, precision, carry-over, selectivity, dilution integrity, and stability. The proposed LC-MS/MS method was applied successfully for the determination of all investigated drugs in spiked human plasma with no significant matrix effect, which is a crucial cornerstone in further therapeutic drug monitoring of newly developed therapeutic agents.     

Solitary wave solutions for some nonlinear time-fractional partial differential equations

In this paper, we have studied the hybrid projective synchronisation for incommensurate, integer and commensurate fractional-order financial systems with unknown disturbance. To tackle the problem of unknown bounded disturbance, fractional-order disturbance observer is designed to approximate the unknown disturbance. Further, we have introduced simple sliding mode surface and designed adaptive sliding mode controllers incorporating with the designed fractional-order disturbance observer to achieve a bounded hybrid projective synchronisation between two identical fractional-order financial model with different initial conditions. It is shown that the slave system with disturbance can be synchronised with the projection of the master system generated through state transformation. Simulation results are presented to ensure the validity and effectiveness of the proposed sliding mode control scheme in the presence of external bounded unknown disturbance. Also, synchronisation error for commensurate, integer and incommensurate fractional-order financial systems is studied in numerical simulation.     

Two validated chromatographic determinations of an antifungal drug,its toxic impurities and degradation product: A comparative study

Tolnaftate, a thionoester anti‐fungal drug, was subjected to alkaline hydrolysis to produce methyl(m‐tolyl)carbamic acid and β ‐naphthol (tolnaftate impurity A). N‐Methyl‐m‐toluidine, tolnaftate impurity D, was synthesized and structurally elucidated along with tolnaftate alkaline degradation products using IR, H¹NMR and MS. Two stability‐indicating HPTLC and RP‐HPLC methods were developed and validated, for the first time, for determination of tolnaftate, its alkaline degradation products and toxic impurities in the presence of methyl paraben, as a preservative in Tinea Cure^® cream. The proposed HPTLC method depended on separation of the studied components on TLC silica gel F₂₅₄ plates using hexane–glacial acetic acid (8:2, v/v) as a developing system and scanning wavelength of 230 nm. The proposed RP‐HPLC method was based on separation of the five components on an Eclipse plus C₁₈ column. The mobile phase used was acetonitrile–water containing 1% ammonium formate (40:60, v/v), with a flow rate of 1 mL/min and detection wavelength of 230 nm. The proposed methods allowed the assay of tolnaftate toxic impurities, β ‐naphthol and N‐methyl‐m‐toluidine, down to 2%, allowing tracing of β ‐naphthol that could be absorbed by the skin causing systemic toxic effects, unlike tolnaftate, indicating the high significance of such determination. International Conference on Harmonization guidelines were followed for validation.     

Synthesis,characterization and DFT calculations of a Re(V)-thiazolidine-2,4-dione complex

This article presents a combined experimental and computational study of a new oxorhenium(V) complex of thiazolidine-2,4-dione (HTDO). The complex has been synthesized by direct reaction of NH₄ReO₄ with thiazolidine-2,4-dione in the presence of Na₂S₂O₆ as a reducing agent. The complex [ReO(TDO)(H₂O)₃](S₂O₈) has been characterized by spectroscopy (FT-IR, NMR, UV-vis, mass), thermogravimetry, microanalysis, and HPL chromatography. The complex was geometrically optimized by DFT with B3LYP level of theory and satisfactory theoretical–experimental agreement was achieved for analysis of IR and NMR data of the complex. Additional information about binding between rhenium and oxo ligand in the complex has been obtained by NBO analysis. The antibacterial activity of the investigated complex has been tested and evaluated.     

Synthesis of Some Novel Heterocyclic Xylidinyl Amines and Carboxamides

The xylidines 1a , 1b undergo condensation with ethyl cyanoacetate 2 and ethyl benzoyl acetate 15 to afford the cyano acetanilides 3a , 3b and the β‐diketones 16a , 16b , respectively. Compounds 3a , 3b react with hydrazine and phenyl hydrazine to afford the azine‐bis derivatives 5a , 5b and 7a , 7b , whereas 16a , 16b react with the same reagents to afford the pyrazolyl amine derivatives 17a , 17b and 18a , 18b , respectively. Compounds 3a , 3b react also with dimethylformamide dimethylacetal to afford the enaminonitriles 8a , 8b , whereas 16a , 16b react with the same reagent to afford only the enaminone 19b . The enaminonitriles 8a , 8b react with hydrazine and phenyl hydrazine to afford also the azine‐bis derivatives 11a , 11b and 14a , 14b , respectively.     

Chromatographic determination of sulfasalazine and its active metabolites: greenness assessment and application to spiked human plasma

Green TLC-densitometric and RP-HPLC methods were developed and validated for the determination of the active prodrug sulfasalazine (SZ), its active metabolite mesalazine (MZ) and the major active metabolite of mesalazine, N-acetyl-5-aminosalicylic acid (AS). In the developed TLC-densitometric method, chromatographic separation was carried out on TLC silica gel plates 60 F₂₅₄ using a developing system consisting of ethyl acetate–methanol–ammonia solution 33% (8:2.5:0.3, by volume) and then scanning the separated bands at 215 nm using hydrochlorothiazide as an internal standard with linearity ranges of 0.4–3, 0.4–2.4 and 0.3–2 for SZ, MZ and AS, respectively. The developed RP-HPLC method depended on chromatographic separation using a C₁₈ column with a solvent mixture of methanol–aqueous acetic acid solution (pH 5) as a mobile phase with gradient elution mode and UV scanning at 243 nm using pyrazinamide as internal standard with linearity ranges of 5–50, 5–40, and 3–20 for SZ, MZ and AS, respectively. US Food and Drug Administration guidelines were followed during validation of the methods. The greenness of the developed methods was estimated using the greenness profile and the Eco-Scale approach. Both methods passed the four quadrants of the greenness profile and had Eco-Scale score ˃75, thus they were considered to be green according to these approaches.     

Analyses of axisymmetric waves in layered piezoelectric rods and their composites

An exact treatment of the propagation of axisymmetric waves in coaxial anisotropic assembly of piezoelectric rod systems is presented. The rod system consists of an arbitrary number of coaxial layers, each possessing transversely isotropic symmetry properties. The treatment, which is based on the transfer matrix technique, is capable of deriving the dispersion relations for a variety of situations. These include the case of a single rod system that is either embedded in an infinitely extended solid or fluid host or kept free. The procedure is also adapted to derive approximate solutions for the cases of a periodic fiber distribution in a matrix material, which model unidirectional fiber-reinforced composites. The results are numerically illustrated for a widely used piezoelectric-polymer composite. It is seen that piezoelectric coupling can significantly change the morphology of the dispersive behavior of the composite.