Nmnat2 attenuates amyloidogenesis as well as up-regulates ADAM10 in AMPK activity-dependent method.

Translation of the hepatitis C virus (HCV) RNA genome is regulated by the internal ribosome entry site (IRES), located in the 5'-untranslated region (5'UTR) and part of the core protein coding sequence, and by the 3'UTR. The 5'UTR has some highly conserved structural regions, while others can assume different conformations. The IRES can bind to the ribosomal 40S subunit with high affinity without any other factors. Nevertheless, IRES activity is modulated by additional cis sequences in the viral genome, including the 3'UTR and the cis-acting replication element (CRE). Canonical translation initiation factors (eIFs) are involved in HCV translation initiation, including eIF3, eIF2, eIF1A, eIF5, and eIF5B. Alternatively, under stress conditions and limited eIF2-Met-tRNAiMet availability, alternative initiation factors such as eIF2D, eIF2A, and eIF5B can substitute for eIF2 to allow HCV translation even when cellular mRNA translation is downregulated. In addition, several IRES trans-acting factors (ITAFs) modulate IRES activity by building large networks of RNA-protein and protein-protein interactions, also connecting 5'- and 3'-ends of the viral RNA. Moreover, some ITAFs can act as RNA chaperones that help to position the viral AUG start codon in the ribosomal 40S subunit entry channel. Finally, the liver-specific microRNA-122 (miR-122) stimulates HCV IRES-dependent translation, most likely by stabilizing a certain structure of the IRES that is required for initiation.Endometriosis is a prevalent gynecologic disease, defined by dysfunctional endometrium-like lesions outside of the uterine cavity. These lesions are presumably established via retrograde menstruation, i.e., endometrial tissue that flows backwards during menses into the abdomen and deposits on the organs. As ongoing pain is one of the main pain symptoms of patients, an animal model that illuminates this problem is highly anticipated. In the present study, we developed and validated a rat model for ongoing endometriosis-associated pain. First, menstrual endometrial tissue was successfully generated in donor rats, as validated by gross examination, histology and qPCR. Next, endometriosis was induced in recipient animals by intraperitoneal injection of menstrual tissue. This resulted in neuro-angiogenesis as well as established endometriosis lesions, which were similar to their human counterparts, since epithelial and stromal cells were observed. Furthermore, significant differences were noted between control and endometriosis animals concerning bodyweight and posture changes, indicating the presence of ongoing pain in animals with endometriosis. In summary, a rat model for endometriosis was established that reliably mimics the human pathophysiology of endometriosis and in which signs of ongoing pain were detected, thus providing a new research tool for therapy development.Although aquaculture has been the fastest growing food sector for decades, there are no standardized parameters for most of the fish species regarding physical meat quality. Therefore, this study provides for the first time an overview of the physical meat characteristics of the most important fish species of the German Baltic Sea coast. Traditional farmed salmonids (rainbow trout (Oncorhynchus mykiss) and maraena whitefish (Coregonus maraena) as well as two percids (European perch, Perca fluviatilis and pikeperch, Sander lucioperca) were utilized for this comparison. The results demonstrate that the meat of the salmonids is very analogous. However, the post mortem degradation process starts faster in trout meat. In contrast, the meat quality characteristics of the percids are relatively different. The meat of pikeperch has comparatively low shear strength with a high water-holding capacity resulting in high meat tenderness. The opposite situation is present in European perch. The results indicate that it is not possible to establish the overall quality characteristics for fish or production form, as there is a high range of variability. Consequently, it is particularly important that meat quality characteristics are developed for important aquaculture species for further improvement through changes in husbandry conditions when necessary.Six platinum(IV) compounds derived from an oxaliplatin analogue containing the unsaturated cyclic diamine trans-1,2-diamino-4-cyclohexene (DACHEX), in place of the 1,2-diaminocyclohexane, and a range of axial ligands, were synthesized and characterized. The derivatives with at least one axial chlorido ligand demonstrated solvent-assisted photoreduction. The electrochemical redox behavior was investigated by cyclic voltammetry; all compounds showed reduction potentials suitable for activation in vivo. X-ray photoelectron spectroscopy (XPS) data indicated an X-ray-induced surface reduction of the Pt(IV) substrates, which correlates with the reduction potentials measured by cyclic voltammetry. read more The cytotoxic activity was assessed in vitro on a panel of human cancer cell lines, also including oxaliplatin-resistant cancer cells, and compared with that of the reference compounds cisplatin and oxaliplatin; all IC50 values were remarkably lower than those elicited by cisplatin and somewhat lower than those of oxaliplatin. Compared to the other Pt(IV) compounds of the series, the bis-benzoate derivative was by far (5-8 times) the most cytotoxic showing that low reduction potential and high lipophilicity are essential for good cytotoxicity. Interestingly, all the complexes proved to be more active than cisplatin and oxaliplatin even in three-dimensional spheroids of A431 human cervical cancer cells.Background and Objectives The effect of supra-inguinal fascia iliaca compartment block (SI-FICB) in hip arthroscopy is not apparent. It is also controversial whether SI-FICB can block the obturator nerve, which may affect postoperative analgesia after hip arthroscopy. We compared analgesic effects before and after the implementation of obturator nerve block into SI-FICB for hip arthroscopy. Materials and Methods We retrospectively reviewed medical records of 90 consecutive patients who underwent hip arthroscopy from January 2017 to August 2019. Since August 2018, the analgesic protocol was changed from SI-FICB to SI-FICB with obturator nerve block. According to the analgesic regimen, patients were categorized as group N (no blockade), group F (SI-FICB only), and group FO (SI-FICB with obturator nerve block). Primary outcome was the cumulative opioid consumption at 24 hours after surgery. Additionally, cumulative opioid consumption at 6 and 12 hours after surgery, pain score, additional analgesic requests, intraoperative opioid consumption and hemodynamic stability, and postoperative nausea and vomiting were assessed. Results Among 87 patients, there were 47 patients in group N, 21 in group F, and 19 in group FO. The cumulative opioid (fentanyl) consumption at 24 hours after surgery was significantly lower in the group FO compared with the group N (N 678.5 (444.0-890.0) µg; FO 482.8 (305.8-635.0) µg; p = 0.014), whereas the group F did not show a significant difference (F 636.0 (426.8-803.0) µg). Conclusion Our findings suggest that implementing obturator nerve block into SI-FICB can reduce postoperative opioid consumption in hip arthroscopy.Malaria is a life-threatening disease and, what is more, the resistance to available antimalarial drugs is a recurring problem. The resistance of Plasmodium falciparum malaria parasites to previous generations of medicines has undermined malaria control efforts and reversed gains in child survival. This paper describes a continuation of our ongoing efforts to investigate the effects against Plasmodium falciparum strains and human microvascular endothelial cells (HMEC-1) of a series of methoxy p-benzyl-substituted thiazinoquinones designed starting from a pointed antimalarial lead candidate. The data obtained from the newly tested compounds expanded the structure-activity relationships (SARs) of the thiazinoquinone scaffold, indicating that antiplasmodial activity is not affected by the inductive effect but rather by the resonance effect of the introduced group at the para position of the benzyl substituent. Indeed, the current survey was based on the evaluation of antiparasitic usefulness as well as the selectivity on mammalian cells of the tested p-benzyl-substituted thiazinoquinones, upgrading the knowledge about the active thiazinoquinone scaffold.Yardlong bean (Vigna unguiculata (L.) Walp. ssp. sesquipedalis), a subgroup of cowpea, is an important vegetable legume crop of Asia where its young pods are consumed in both fresh and cooked forms. Pod fiber contents (cellulose, hemicellulose and lignin) correlates with pod tenderness (softness/hardness) and pod shattering. In a previous study using populations derived from crosses between yardlong bean and wild cowpea (V. unguiculata ssp. unguiculata var. spontanea), three major quantitative trait loci (QTLs), qCel7.1, qHem7.1 and qLig7.1, controlling these fibers were identified on linkage group 7 (cowpea chromosome 5) and are co-located with QTLs for pod tenderness and pod shattering. The objective of this study was to identify candidate gene(s) controlling the pod fiber contents. Fine mapping for qCel7.1, qHem7.1 and qLig7.1 was conducted using F2 and F23 populations of 309 and 334 individuals, respectively, from the same cross combination. New DNA markers were developed from cowpea reference genome sequence and used for fine mapping. A QTL analysis showed that in most cases, each pod fiber content was controlled by one major and one minor QTLs on the LG7. The major QTLs for cellulose, hemicellulose and lignin in pod were always mapped to the same regions or close to each other. In addition, a major QTL for pod shattering was also located in the region. Although there were several annotated genes relating to pod fiber contents in the region, two genes including Vigun05g266600 (VuBGLU12) encoding a beta glucosidase and Vigun05g273500 (VuMYB26b) encoding a transcription factor MYB26 were identified as candidate genes for the pod fiber contents and pod shattering. Function(s) of these genes in relation to pod wall fiber biosynthesis and pod shattering was discussed.Engineered tissue-like structures often instigate an inflammatory response in the host that can inhibit wound healing and ultimately lead to the rejection of the implant. In our previous study, we have characterized the properties and biocompatibility of novel multiparticulate drug delivery systems (MDDS), based on collagen matrix with gradual release of anti-inflammatory drug flufenamic acid, we evaluated their anti-inflammatory potential and demonstrated their efficiency against burns and soft tissue lesions. In addition to these results, FA was previously described as a stimulant for adipogenesis, therefore we hypothesized that MDDS might also be appropriate for adipose tissue engineering. After the cell-scaffold constructs were obtained, cell morphology, adhesion and spreading on the systems were highlighted by scanning electron microscopy, immunostaining and confocal microscopy. The effect of FA-enriched materials on adipogenesis was evaluated at gene and protein level, by RT-qPCR, confocal microscopy and immunohistochemistry.read more