sensitivity of erstwhile resistant cells, increased Bax/Bcl-2 apoptotic ratio, while suppressing oncogenicity and clonogenicity. We provide preclinical evidence implicating PDK1 as an active driver of IR-resistance by activation of the PI3K/AKT/mTOR signaling, up-modulation of cancer stemness signaling and suppression of DNA damage, thus, projecting PDK1-targeting as a putative enhancer of radiosensitivity and a potential new therapeutic approach for patients with IR-resistant HCC.Neochlorogenic acid (nCGA) is a phenolic compound isolated from mulberry leaf (Morus alba L.), which possesses multiple pharmacological activities containing antioxidant and anti-inflammatory effects. However, the role of nCGA in the treatment of acute pneumonia and the underlying molecular mechanism are still unclear. Hence, the aim of study is to investigate the anti-inflammatory properties of nCGA on LPS-stimulated inflammation in A549 cells. In the present study, results reported that nCGA without cytotoxicity significantly reduced the production of TNF-α, IL-6, and NO, and further suppressed the proteins of iNOS, COX2, TNF-α, IL-6 expression. Furthermore, nCGA also inhibited NF-κB activation and blocked MAPKs signaling pathway phosphorylation. In addition, we found nCGA significantly increased the expression of HO-1 via activating the AMPK/Nrf2 signaling pathway to attenuate the inflammatory response, whereas this protective effect of nCGA was reversed by pre-treatment with compound C (C.C, an AMPK inhibitor). Therefore, all these results indicated that nCGA might act as a natural anti-inflammatory agent for the treatment of acute pneumonia.Melanization is a common phenomenon in insects, and melanin synthesis is a conserved physiological process that occurs in epidermal cells. Moreover, a comprehensive understanding of the mechanisms of melanin synthesis influencing insect pigmentation are well-suited for investigating phenotype variation. The Asian multi-colored (Harlequin) ladybird beetle, Harmonia axyridis, exhibits intraspecific polymorphism based on relative levels of melanization. However, the specific characteristics of melanin synthesis in H. All-trans Retinoic Acid purchase axyridis remains elusive. link2 In this study, we performed gene-silencing analysis of the pivotal inverting enzyme, tyrosine hydroxylase (TH), and DOPA decarboxylase (DDC) in the tyrosine metabolism pathway to investigate the molecular and regulatory mechanism of melanin synthesis in H. axyridis. Using RNAi of TH and DDC genes in fourth instar larvae, we demonstrated that dopamine melanin was the primary contributor to the overall body melanization of H. axyridis. Furthermore, our study provides the first conclusive evidence that dopamine serves as a melanin precursor for synthesis in the early pupal stage. According to transcription factor Pannier, which is essential for the formation of melanic color on the elytra in H. axyridis, we further demonstrated that suppression of HaPnr can significantly decrease expression levels of HaTH and HaDDC. These results in their entirety lead to the conclusion that transcription factor Pannier can regulate dopamine melanin synthesis in the dorsal elytral epidermis of H. axyridis.The present study aimed to investigate the effects of astaxanthin (ASX) on ochratoxin A (OTA)-induced renal oxidative stress and its mechanism of action. Serum kidney markers, histomorphology, ultrastructural observation, and oxidative stress indicators were assessed. Meanwhile, quantitative real-time reverse transcription PCR and western blotting detection of NRF2 (encoding nuclear factor, erythroid 2 like) and members of the NRF2/KEAP1 signaling pathway (KEAP1 (encoding Kelch-like ECH-associated protein), NQO1 (encoding NAD(P)H quinone dehydrogenase), HO-1 (encoding heme oxygenase 1), γ-GCS (gamma-glutamylcysteine synthetase), and GSH-Px (glutathione peroxidase 1)) were performed. Compared with the control group, the OTA-treated group showed significantly increased levels of serum UA (uric acid) and BUN (blood urea nitrogen), tubular epithelial cells were swollen and degenerated, and the levels of antioxidant enzymes decreased significantly, and the expression of NRF2 (cytoplasm), NQO1, HO-1, γ-GCS, and GSH-Px decreased significantly. More importantly, after ASX pretreatment, compared with the OTA group, serum markers were decreased, epithelial cells appeared normal; the expression of antioxidant enzymes increased significantly, NQO1, HO-1, γ-GCS and GSH-Px levels increased significantly, and ASX promoted the transfer of NRF2 from the cytoplasm to the nucleus. These results highlight the protective ability of ASX in renal injury caused by OTA exposure, and provide theoretical support for ASX’s role in other mycotoxin-induced damage.Utilization of arbuscular mycorrhizal fungi (AMF) for enhancing growth and development as well as production of essential oil in aromatic plants has been increasingly drawing research interest. In order to assess the AMF effects on different aromatic species, an open-field experiment was carried out using Artemisia dracunculus (tarragon), Lavandula angustifolia (lavender) and Hyssopus officinalis (hyssop). AMF stimulated the growth of tarragon and lavender plants, whereas hyssop showed a slight developmental slowing; nonetheless, a significant increase in essential oil content in the three species was seen. AMF application increased the biomass of A. dracunculus and H. officinalis by 20-35%. No differences in antioxidant activity and phenolics content were recorded at harvest between the control and AMF-inoculated plants, but the latter showed a significant increase in antioxidant status upon storage at high temperature and humidity compared to the untreated control. The enhancement of abiotic stress resistance during storage in plants inoculated with AMF was the highest in A. dracunculus, and the lowest in H. officinalis, while the untreated control plants showed a significant decrease in phenolics, ascorbic acid and chlorophyll content, as well as antioxidant activity, upon the abiotic stress. AMF inoculation differentially affected the mineral composition, increasing the accumulation of Se, I and Zn in A. dracunculus, and decreasing the levels of heavy metals and Co, Fe, Li, Mn in H. officinalis. Based on the outcome of the present research, AMF inoculation resulted in a significant enhancement of the overall performances of A. dracunculus, L. link3 angustifolia and H. officinalis, and also in the improvement of plant antioxidant status upon storage in stress conditions.Safinamide is an approved drug for the treatment of motor fluctuations in Parkinson’s disease (PD). Scarce data are available on its use in clinical practice. A group of Spanish movement disorders specialists was convened to review the use of safinamide across different clinical scenarios that may guide neurologists in clinical practice. Eight specialists with recognized expertise in PD management elaborated the statements based on available evidence in the literature and on their clinical experience. The RAND/UCLA method was carried, with final conclusions accepted after a 2-round modified Delphi process. Higher level of agreement between panellists was reached for the following statements. Safinamide significantly improves mean daily OFF time without troublesome dyskinesias. Adjunctive treatment with safinamide is associated with motor improvements in patients with mid-to-late PD. The efficacy of safinamide on motor fluctuations is maintained at long-term, with no increase over time in dyskinesias severity. The clinical benefits of safinamide on pain and depression remain unclear. Safinamide presents a similar incidence of adverse events compared with placebo. The efficacy and safety of safinamide shown in the pivotal clinical trials are reproduced in clinical practice, with improvement of parkinsonian symptoms, decrease of daily OFF time, control of dyskinesias at the long term, and good tolerability and safety.Recent years have seen significant improvements in the understanding of functional soft matter […].Human RNASET2 acts as a powerful oncosuppressor protein in in vivo xenograft-based murine models of human cancer. Secretion of RNASET2 in the tumor microenvironment seems involved in tumor suppression, following recruitment of M1-polarized macrophages. Here, we report a murine Rnaset2-based syngeneic in vivo assay. BALB/c mice were injected with parental, empty vector-transfected or murine Rnaset2-overexpressing mouse C51 or TS/A syngeneic cells and tumor growth pattern and immune cells distribution in tumor mass were investigated. Compared to control cells, mouse Rnaset2-expressing C51 cells showed strong delayed tumor growth. CD86+ M1 macrophages were massively recruited in Rnaset2-expressing C51-derived tumors, with concomitant inhibition of MDSCs and CD206+ M2 macrophages recruitment. At later times, a relevant expansion of intra-tumor CD8+ T cells was also observed. After re-challenge with C51 parental cells, most mice previously injected with Rnaset2-expressing C51 cells still rejected C51 tumor cells, suggesting a Rnaset2-mediated T cell adaptive immune memory response. These results point at T2 RNases as evolutionary conserved oncosuppressors endowed with the ability to inhibit cancer growth in vivo through rebalance of intra-tumor M1/M2 macrophage ratio and concomitant recruitment of adaptive anti-tumor CD8+ T cells.On magnetic resonance (MR) imaging, Modic type 1 (MT1) endplate changes and infectious spondylodiscitis share similar findings. Therefore, this study investigated vertebral bone marrow and endplate changes to enable their differentiation. The lumbar spine MR examinations of 91 adult patients were retrospectively included 39 with MT1; 19 with early spondylodiscitis without abscess; and 33 with advanced spondylodiscitis with abscess. The assessment included percentage of bone marrow edema on sagittal short tau inversion recovery images, and the signal ratio of edema to unaffected bone and endplate contour (normal; irregular, yet intact; blurred; destructive) on sagittal unenhanced T1-weighted images. Differences were tested for statistical significance by Chi-square test and mixed model analysis of variance. The MR diagnostic accuracy in differentiating MT1 and spondylodiscitis was assessed by cross-tabulation and receiver-operating characteristic analysis. The endplate contours, edema extents, and T1-signal ratios of MT1 (extent, 31.96%; ratio, 0.83) were significantly different (p less then 0.001) from early spondylodiscitis (56.42%; 0.60), and advanced spondylodiscitis (91.84%; 0.61). The highest diagnostic accuracy (sensitivity, 94.87%; specificity, 94.23%; accuracy, 94.51%) in identifying MT1 was provided by an irregular, yet intact endplate contour. This may be a useful MR feature for the differentiation between MT1 and spondylodiscitis, particularly in its early stage.The availability of autologous adult stem cells is one of the essential prerequisites for human stem cell therapy. Urine-derived stem cells (USCs) are considered as desirable cell sources for cell therapy because donor-specific USCs are easily and non-invasively obtained from urine. Efficient isolation, expansion, and differentiation methods of USCs are necessary to increase their availability. Here, we developed a method for efficient isolation and expansion of USCs using Matrigel, and the rho-associated protein kinase (ROCK) inhibitor, Y-27632. The prepared USCs showed significantly enhanced migration, colony forming capacity, and differentiation into osteogenic or chondrogenic lineage. The USCs were successfully reprogramed into induced pluripotent stem cells (USC-iPSCs) and further differentiated into kidney organoid and hematopoietic progenitor cells (HPCs). Using flavonoid molecules, the isolation efficiency of USCs and the production of HPCs from the USC-iPSCs was increased. Taken together, we present an improved isolation method of USCs utilizing Matrigel, a ROCK inhibitor and flavonoids, and enhanced differentiation of USC-iPSC to HPC by flavonoids.