Diabetes induced renal complications by leukocyte activation of nuclear factor κ-B and its regulated genes expression.

Type 2 diabetes mellitus (T2D) is a metabolic disorder characterized by inappropriate insulin function. Despite wide progress in genome studies, defects in gene expression for diabetes prognosis still incompletely identified. Prolonged hyperglycemia activates NF-κB, which is a main player in vascular dysfunctions of diabetes. Activated NF-κB, triggers expression of various genes that promote inflammation and cell adhesion process. Alteration of pro-inflammatory and profibrotic gene expression contribute to the irreversible functional and structural changes in the kidney resulting in diabetic nephropathy (DN). To identify the effect of some important NF-κB related genes on mediation of DN progression, we divided our candidate genes on the basis of their function exerted in bloodstream into three categories (Proinflammatory; NF-κB, IL-1B, IL-6, TNF-α and VEGF); (Profibrotic; FN, ICAM-1, VCAM-1) and (Proliferative; MAPK-1 and EGF). We analyzed their expression profile in leukocytes of patients and explored their correlation to diabetic kidney injury features. Our data revealed the overexpression of both proinflammatory and profibrotic genes in DN group when compared to T2D group and were associated positively with each other in DN group indicating their possible role in DN progression. In DN patients, increased expression of proinflammatory genes correlated positively with glycemic control and inflammatory markers indicating their role in DN progression. Our data revealed that the persistent activation NF-κB and its related genes observed in hyperglycemia might contribute to DN progression and might be a good diagnostic and therapeutic target for DN progression. Large-scale studies are needed to evaluate the potential of these molecules to serve as disease biomarkers.

In vivo glucose-6-phosphatase inhibitory, toxicity and antidiabetic potentials of 2-picolylamine thioureas in Swiss albino mice.

The 2-picolylamine is a simplest analogue of the alkaloid that has secondary and tertiary nitrogen function in its cyclic structure like that of alkaloids that can be derivatized to a number of biologically active compounds. In connection to our previous work, in the present work, three thiourea derivatives (I = 1,3-bis(2-benzyl-3-phenyl-1-(pyridine-2-yl) propyl) thiourea, II = 1,3-bis (pyridin-2-ylmethyl) thiourea, and III = 1-(2-benzyl-3-phenyl-1-(pyridine-2-yl) propyl)-3-phenylthiourea) were synthesized using 2-picolylamine template which is a readily available synthetic analogue of naturally occurring alkaloid. The biological effect of the synthesized derivatives were monitored on the activity of glucose-6-phosphatase in Swiss albino mice (21-days). The derivatives were also tested for their potential toxicity in a 28-days sub-chronic toxicity studies by assessing their effects on different parameters like hematological, serum biochemistry and liver histology. The therapeutic effect of the safe derivative (I) was examined in streptozotocin-induced diabetic mice as well. The derivatives showed inhibition of the enzyme activity from good to an excellent degree. Compound I had the highest inhibition with 21.42 ± 5.113 mg of the released phosphate as compared to that of the positive control group (84.55 ± 3.213 mg). Only I turned out to be safe for use in animals without exerting any toxic or lethal effects on any of the assessed parameters in the used animal model. Compound I efficiently reversed the effects like hyperglycemia, hyperlipidemia and weight loss in the test animals. Out of these three-tested compounds, I was found safe to be use as therapeutic agent in diabetes complications. However, further toxicological studies in other animal models are needed as well.

Natural deep eutectic solvent supported targeted solid-liquid polymer carrier for breast cancer therapy.

Solid-liquid nanocarriers (SLNs) are at the front of the rapidly emerging field of medicinal applications with a potential role in the delivery of bioactive agents. Here, we report a new SLN of natural deep eutectic solvent (NADES) and biotin-conjugated lysine-polyethylene glycol copolymer. The SLN system was analyzed for its functional groups, thermal stability, crystalline nature, particle size, and surface morphology through the instrumental analysis of FT-IR, TGA, XRD, DLS, SEM, and TEM. Encapsulation of PTX (paclitaxel) and 7-HC (7-hydroxycoumarin) with the SLN was carried out by dialysis, and UV-visible spectra evidenced the drug loading capacity and higher encapsulation efficiency obtained. The enhanced anticancer potential of PTX- and 7-HC-loaded SLN was assessed in vitro, and the system reduces the cell viability of MDA-MB-231 cells. The PTX- and 7-HC-loaded SLN system was investigated in a breast cancer-induced rat model via in vivo studies. It shows decreased lysosomal enzymes and increased levels of caspase to cure breast tumors. It very well may be reasoned that the designed PTX- and 7-HC-loaded SLN system has strong anticancer properties and exhibits potential for delivery of drug molecules in cancer treatment.