No abstract

We pinpoint important key genes and pathways closely related with breast cancer-associated fibroblasts initiation and progression by a series of bioinformatics analysis on DEGs. These screened genes and pathways provided for a more detailed molecular mechanism underlying breast cancer-associated fibroblasts occurrence and progression, holding promise for acting as molecular markers and probable therapeutic targets.

Repaglinide is an anti-diabetic, oral blood-glucose lowering drug of the meglitinide class used in the management of type-II diabetes mellitus. The present investigation was concerned with the development of the floating matrix tablets, which after oral administration are designed to prolong the gastric residence time and thus, improve the bioavailability of the drug as well as its half life. Repaglinide showed maximum absorption at wavelength 244 nm in 0.5N HCl. Drug-polymer compatibility studies by FT-IR gave confirmation about their purity and showed no interaction between drug and selected polymers. Various formulations were developed by using release rate controlling and gel forming polymers like HPMC (K-4M, K-15M & K-100M) by direct compression method with the incorporation of sodium bicarbonate as gas generating agent. All the formulations had floating lag time below 47.5 seconds and constantly exhibited floating on dissolution medium for more than 24 h. swelling studies indicated significant water uptake and contributed in drug release. The formulation with HPMC K4M (F1, F2 & F3) showed drug release rate between 96 to 99%. The use of HPMC K15M (F4, F5 & F6) have shown drug release rate from 89.3 to 98.2% and formulations with HPMC K100M (F7, F8 & F9) have shown drug release rate between 72 to 84%. From among all the developed formulations, as formulation F5-99% released the drug for longer period of time and it had slightly less floating lag time as compared to other formulations. So, it was selected as the best formulation. It was concluded that the drug release followed zero order kinetic, as the correlation coefficient (R2 value) was higher for zero order release.

The formulation of sublingual tablets of Ondansetron HCl was carried out by using direct compression technique and evaluation tests were carried out as per pharmacopoeial specifications. Poor compressibility problem of Mannitol was overcome by coprocessing it with maltose and corn starch in varying ratios. The results of evaluation tests indicate that the ratio of Mannitol: Maltose: Corn starch: 19:2:1 gave better tableting performance with respect to precompression & postcompression parameters. It was also observed that increase in maltose content, increased the hardness but negatively affects disintegration and drug release and vice versa. Furthermore the study on effect of superdisintgrants shows that Crospovidone gives faster disintegration and satisfactory drug release in concentration of 4% compared to that of Sodium starch glycolate & Croscarmelose sodium. Formulation using a bioadhesive polymer PVP K 30 in ratio of 0.5% showed uniform release of drug over a period of 20 minutes with complete solubilization of tablet compared to that of gelatin and carbopol 934. On numerical optimization of prepared formulations, three formulations were suggested by Design Expert 8.0.7.1(Trial Version), among that Formulation B gave better correlation between predicted value and observed value. Thus Formulation B was chosen as global best formulation.

In the present investigation, we have carried out the isolation of fungal endophytes from Centella asiatica Linn leaves followed by fermentation and extraction of fungal endophytes with non-polar solvents such as chloroform, ethyl acetate and n-butanol. Preliminary phytochemical investigation of endophytic crude fractions of leaves were also determined to detect the presence of primary and secondary metabolites followed by invitro free radical scavenging activity by reducing power, DPPH and hydroxyl radical assay. The chloroform fungal endophytic fractions were subjected to column chromatography by gradient elution technique for isolation of possible secondary metabolite. Reducing power of endophytic extracts of C. asiatica Leaf (CAL-1) (50-450µg/ml) increased with increase in concentration. Reaction with DPPH radicals of CAL-1 showed good scavenging activity. The IC 50 values for Ascorbic acid, chloroform extract, ethyl acetate extract and n-butanol extract were found to be 30.33 µg /ml, 66.58 µg/ml, 79.33 µg /ml and 96.39 µg/ml respectively. In hydroxyl radical assay, The IC 50 values for mannitol, chloroform extract, ethyl acetate extract and n-butanol extract were found to be 121.06 µg / ml, 141.21 µg/ml, 181.80 µg/ml and 189.90 µg/ml respectively. The endophytic crude fractions of ethyl acetate exhibited potent antioxidant activity as compared to other fractions. Hence, ethyl acetate fungal endophytic fractions of Centella asiatica Linn leaves can be employed as a potential antioxidant in the prevention of oxidative stress caused by the free radicals.