TGF-ß signaling: A recap of SMAD-independent and SMAD-dependent pathways.

Transforming growth factor-ß (TGF-ß) is a proinflammatory cytokine known to control a diverse array of pathological and physiological conditions during normal development and tumorigenesis. TGF-ß-mediated physiological effects are heterogeneous and vary among different types of cells and environmental conditions. TGF-ß serves as an antiproliferative agent and inhibits tumor development during primary stages of tumor progression; however, during the later stages, it encourages tumor development and mediates metastatic progression and chemoresistance. The fundamental elements of TGF-ß signaling have been divulged more than a decade ago; however, the process by which the signals are relayed from cell surface to nucleus is very complex with additional layers added in tumor cell niches. Although the intricate understanding of TGF-ß-mediated signaling pathways and their regulation are still evolving, we tried to make an attempt to summarize the TGF-ß-mediated SMAD-dependent andSMAD-independent pathways. This manuscript emphasizes the functions of TGF-ß as a metastatic promoter and tumor suppressor during the later and initial phases of tumor progression respectively.

Impact of spray drying conditions on the reconstitution, efficiency and flow properties of spray dried apple powder-optimization, sensorial and rheological assessment.

Spray drying is a preferred choice for development of highly soluble, rapidly dispersible apple powder. However, adhesion during spray drying of syrups and juices is encountered which leads to product loss. The main solution to reduce adhesion is using drying aids. Besides, control of spray drying operating parameters (inlet air temperature and feed flow rate) also closely govern the powder yield, physical, functional and microstructural properties of spray dried fruit powder. Thus, the aim of the study was to evaluate the effect of inlet air temperature (IAT), carrier agent concentration (MD:GA), feed flow rate (FFR) & feed TSS (FTSS) on moisture content, hygroscopicity, dispersibility, water solubility index (WSI), bulk density (BD), porosity (Φ), flowability, lightness (L*) and radical scavenging activity (RSA). Design expert predicted IAT of 160 °C, MD and GA concentration of 14% and 6% respectively, FFR of 350 rpm & FTSS of 15oBrix as optimum condition for development of easily dispersible, highly soluble and least hygroscopic powder. The powder developed after following the optimized condition (SDAP) recorded moisture content as 2.91%, hygroscopicity as 25.29%, dispersibility as 92.50%, WSI as 94.17%, bulk density as 314.1 kg/m3, porosity as 57.19, flowability as 25.83°, L* value as 70.54 and RSA as 14.37. Among different powder reconstitution concentrations, 25% w/v concentration came out to be the best for reconstitution on the basis of sensory evaluation and rheological test. Frequency sweep test for all the reconstituted juice samples showed higher storage modulus than loss modulus for all the applied frequencies. The results of the study conferred that the developed powder could be used for commercial purpose.

Growth inhibition by bupivacaine is associated with inactivation of ribosomal protein S6 kinase 1.

Bupivacaine is an amide type long acting local anesthetic used for epidural anesthesia and nerve blockade in patients. Use of bupivacaine is associated with severe cytotoxicity and apoptosis along with inhibition of cell growth and proliferation. Although inhibition of Erk, Akt, and AMPK seemingly appears to mediate some of the bupivacaine effects, potential downstream targets that mediate its effect remain unknown. S6 kinase 1 is a common downstream effector of several growth regulatory pathways involved in cell growth and proliferation known to be affected by bupivacaine. We have accordingly attempted to relate the growth inhibitory effects of bupivacaine with the status of S6K1 activity and we present evidence that decrease in cell growth and proliferation by bupivacaine is mediated through inactivation of S6 kinase 1 in a concentration and time dependent manner. We also show that ectopic expression of constitutively active S6 kinase 1 imparts substantial protection from bupivacaine induced cytotoxicity. Inactivation of S6K1 though associated with loss of putative mTOR mediated phosphorylation did not correspond with loss of similar phosphorylations in 4EBP1 indicating that S6K1 inhibition was not mediated through inactivation of mTORC1 signaling pathway or its down regulation.