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Human immunodeficiency viruses in 321 samples from tenofovir-naïve patients were retrospectively evaluated for resistance to this nucleotide analogue. All virus strains with insertions between amino acids 67 and 70 of the reverse transcriptase (n ‫؍‬ 6) were highly resistant. Virus strains with the Q151M mutation were divided into susceptible (n ‫؍‬ 12) and highly resistant (n ‫؍‬ 8) viruses. This difference was due to the absence or presence of the K65R mutation, which was confirmed by site-directed mutagenesis.

Pruritus is a common and disabling symptom in patients with hepatobiliary disorders, particularly in those with cholestatic features. Serum levels of lysophosphatidic acid (LPA) and its forming enzyme autotaxin were increased in patients suffering from hepatic pruritus, correlated with itch severity and response to treatment. Here we show that in a culture of dorsal root ganglia LPA 18:1 surprisingly activated a large fraction of satellite glia cells, and responses to LPA 18:1 correlated inversely with responses to neuronal expressed transient receptor potential channels. LPA 18:1 caused only a marginal activation of heterologously expressed TRPV1, and responses in dorsal root ganglion cultures from TRPV1-deficient mice were similar to controls. LPA 18:1 desensitized subsequent responsiveness to chloroquine and TGR5 agonist INT-777. The LPA 18:1-induced increase in cytoplasmatic calcium stems from the endoplasmatic reticulum. LPA receptor expression in dorsal root ganglia and Schwann cells, LPAR1 immunohistochemistry, and pharmacological results indicate a signaling pathway through LPA receptor 1. Peripheral ratSchwann cells, which are of glial lineage as the satellite glia cells, were also responsive to LPA 18:1. Summarizing, LPA 18:1 primarily activates rather glial cells than neurons, which may subsequently modulate neuronal responsiveness and sensory sensations such as itch and pain.

In this study mesoporous silica SBA-15 was evaluated as a vehicle for the transport of cytotoxic natural product emodin (EO). SBA-15 was loaded with different quantities of EO (SBA-15|EO1–SBA-15|EO5: 8–36%) and characterized by traditional methods. Several parameters (stabilities) and the in vitro behavior on tumor cell lines (melanoma A375, B16 and B16F10) were investigated. SBA-15 suppresses EO release in extremely acidic milieu, pointing out that EO will not be discharged in the stomach. Furthermore, SBA-15 protects EO from photodecomposition. In vitro studies showed a dose dependent decrease of cellular viability which is directly correlated with an increasing amount of EO in SBA-15 for up to 27% of EO, while a constant activity for 32% and 36% of EO in SBA-15 was observed. Additionally, SBA-15 loaded with EO (SBA-15|EO3) does not disturb viability of peritoneal macrophages. SBA-15|EO3 causes inhibition of tumor cell proliferation and triggers apoptosis, connected with caspase activation, upregulation of Bax, as well as Bcl-2 and Bim downregulation along with amplification of poly-(ADP-ribose)-polymerase (PARP) cleavage fragment. Thus, the mesoporous SBA-15 is a promising carrier of the water-insoluble drug emodin.