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Qualitative ego systems within health occupations training: Capturing the self regarding others.
Ligustrazine (or Tetramethylpyrazine, TMP) is an active pharmaceutical ingredient that faces the challenges of bitter taste and low oral bioavailability by the commercial phosphate salt (TMP-Pho). We tackled these challenges by forming salts with two sweeteners, acesulfame (Acs) and saccharine (Sac). Both salts effectively masked the bitter taste of TMP. Compared to TMP-Pho, TMP-Sac shows 43% lower solubility and 11% lower permeability while TMP-Acs shows higher (two-fold) solubility but 24% lower permeability. Both TMP-Acs and TMP-Sac exhibited approximately 40% higher bioavailability through reducing the rate of TMP absorption. Thus, salt formation with both sweeteners simultaneously addressed the challenges brought about by the bitter taste and lower bioavailability of TMP. Docetaxel (DTX), a widely prescribed anticancer agent, is now associated with increased instances of multidrug resistance. Also, being a problematic BCS class IV drug, it poses challenges for the formulators. Henceforth, it was envisioned to synthesize an analogue of DTX with a biocompatible lipid, i.e., palmitic acid. The in-silico studies (molecular docking and simulation) inferred lesser binding of docetaxel palmitate (DTX-PL) with P-gp vis-à-vis DTX and paclitaxel, indicating it to be a poor substrate for P-gp efflux. Solid lipid nanoparticles (SLNs) of the conjugate were prepared using various lipids, viz. palmitic acid, stearic acid, cetyl palmitate and glyceryl monostearate. The characterization studies for the nanocarrier were performed for the surface charge, drug payload, micromeritics, release pattern of drug and surface morphology. From the cytotoxicity assays on resistant MCF-7 cells, it was established that the new analogue offered substantially decreased IC50 to that of DTX. Further, apoptosis assay also corroborated the results obtained in IC50 determination wherein, SA-SLNs showed the highest apoptotic index than free DTX. The conjugate not only enhanced the solubility but also offered lower plasma protein binding and improved pharmacokinetic and pharmacodynamic effect for DTX loaded SA-SLNs in apt animal models, and lower affinity to P-gp efflux. The studies provide preliminary evidence and a ray of hope for a better candidate in its nano version for safer and effective cancer chemotherapy. Tumor growth and metastasis are multistep processes regulated by multiple signaling pathways. The successful treatment of cancer largely depends on the ability to inhibit metastatic process. Multiphase inhibition of metastasis is a promising approach. Here, we described a targeting delivery system which was constructed by mixing hyaluronic acid-d-α-tocopheryl succinate (HA-TOS, HT) and low molecular weight heparin-TOS (LMWH-TOS, LT) to form a stable hybrid micelle (HT-LT), encapsulating chemotherapeutic drug doxorubicin (DOX). The prepared HT-LT NPs was about 125 nm in diameter with high drug encapsulation rate and continuous drug release behavior. We confirmed that HT-LT NPs exhibited an effective targeting ability both in vitro and in vivo using a 4T1 model that was attributed to HA binding to CD44 receptors. In addition, HT-LT NPs acted on different phases of the invasion-metastasis cascade and inhibited tumor cell migration and invasion, thus inhibiting tumor metastasis. This combinatorial strategy provided an alternative approach for triple negative breast cancer therapy. Sucrose utilization has been established in Escherichia coli strains by expression of Mannheimia succiniciproducens β-fructofuranosidase (SacC), which hydrolyzes sucrose into glucose and fructose. Recombinant E. coli strains that can utilize sucrose were examined for their abilities to produce poly(3-hydroxybutyrate) [P(3HB)] and poly(3-hydroxybutyrate-co-lactate) [P(3HB-co-LA)] from sucrose. When recombinant E. coli strains expressing Ralstonia eutropha PhaCAB and SacC were cultured in MR medium containing 20 g/L of sucrose, all recombinant E. coli strains could produce P(3HB) from sucrose. Also, recombinant E. coli strains expressing Pseudomonas sp. MBEL 6-19 PhaC1437, Clostridium propionicum Pct540, R. SMS 201-995 in vitro eutropha PhaAB enzymes along with SacC could produce P(3HB-co-LA) from sucrose. Among the examined E. coli strains, recombinant E. coli XL1-Blue produced the highest contents of P(3HB) (53.60 ± 2.55 wt%) and P(3HB-co-LA) (29.44 ± 0.39 wt%). In the batch fermentations, recombinant E. coli XL1-Blue strains completely consumed 20 g/L of sucrose as the sole carbon source and supported the production of 3.76 g/L of P(3HB) and 1.82 g/L of P(3HB-co-LA) with 38.21 wt% P(3HB) and 20.88 wt% P(3HB-co-LA) contents, respectively. Recombinant E. coli strains developed in this study can be used to establish a cost-efficient biorefinery for the production of polyhydroxyalkanoates (PHAs) from sucrose, which is an abundant and inexpensive carbon source. The high-pressure homogenization (HPH) was used as a post-treatment after acid hydrolysis to alter the morphology and physical properties of ginkgo seed shells cellulose and the resulting nanocellulose were applied to stabilize O/W Pickering emulsions. The length of nanocellulose decreased from 1500 nm to 406 nm with the increasing of homogenization pressure from 10 to 70 MPa. The shorter nanocellulose exhibited higher hydrophobicity and was beneficial for reducing interfacial tension between oil and water. The suspension of longer nanocellulose exhibited a fluid gel behavior. The length of nanocellulose affected the surface coverage ratio of emulsions, which long nanocellulose leaded to a low coverage ratio and short nanocellulose caused a high coverage ratio. Emulsions containing oil phase ranging from 10 to 70% (v/v) could be prepared by only small amounts of nanocellulose treated by 50 MPa (C-50). In addition, the emulsions showed benign stability against a wide range of temperature, pH, and ionic strength environments. The results indicated C-50 not only has the similar amphipathic properties as the cellulose nanocrystals, but also has a relatively long size, showing the property of being as entangled with each other as cellulose nanofibers to form a network structure.
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