Zobrazení zdroje stránky Jensbydudley5469

Leptus (Leptus) grancanaricus n. sp. and L. (L.) machadoi n. sp. are described from Gran Canaria and Fuerteventura (Canary Islands). They were collected from new hosts for the genus Leptus Herpisticus guanarteme Machado and Laparocerus maxorata Machado (Coleoptera Curculionidae). New metrical data for Leptus (Leptus) andae, L. (L.) akkus, L. (L.) hammameticus, L. (L.) horiacus and L. (L.) tammuzi based on examination on the type-material are provided.Apoptosis/cell death and reactive oxygen species (ROS) via overload free Ca2+ and Zn2+ uptake into mitochondria are emerging as crucial events in the etiology of hypoxia (HPX)-induced neurodegenerative diseases. The neuroprotective actions of curcumin (CURC) via modulation of oxidative stress and the PARP1-dependent activated TRPM2 cation channel on the ROS generation and cell death in several neurons have been recognized. However, the molecular mechanisms underlying CURC's neuroprotection remain elusive. We investigated the role of CURC via modulation of TRPM2 on cell death and oxidative cytotoxicity in SH-SY5Y neuronal cells. The SH-SY5Y cells were divided into five groups as follows CURC (10 µM for 24 h), HPX (200 µM CoCl2 for 24 h), CURC + HPX, and HPX + TRPM2 blockers (2-APB-100 µM or ACA-25 µM for 30 min). In some experiments, the cells in the HPX groups were additionally incubated with PARP1 (PJ34) and Zn2+ (TPEN) inhibitors. The exposure of CoCl2 induced increases of TRPM2 current density and Ca2+ fluorescence intensity with an increase of mitochondrial membrane depolarization and ROS generation. When HPX-induced TRPM2 activity was blocked by 2-APB and ACA, or the cells were treated with CURC, the increase of ROS generation, the expression levels of TRPM2 and PARP1 were restored. The levels of apoptosis and cell death in the cells were enriched with increases of caspase-3 and -9 activations, although they were decreased by CURC treatment. HPX-induced increase of cytosolic Zn2+ was attenuated by the TPEN and CURC treatments. In conclusion, CURC attenuates HPX-induced mitochondrial ROS generation, apoptosis, cell death, and TRPM2-mediated Ca2+ signaling and may provide an avenue for treating HPX-induced neurological diseases associated with the ROS, Ca2+, and Zn2+.Anesthetic-induced cognitive impairment has been observed clinically. The mechanism underlying anesthetic-induced cognitive impairment is closely associated with neuronal apoptosis and neuroinflammation. Ramelteon is a potent and highly selective melatonin receptor agonist that has been used for the treatment of insomnia and has been reported to have an anti-inflammatory effect. [https://www.selleckchem.com/products/linderalactone.html this website] In this study, we aimed to investigate the protective effects of Ramelteon against the cytotoxicity induced by isoflurane in brain microvascular endothelial cells. Our results show that Ramelteon ameliorated oxidative stress by suppressing the generation of mitochondrial reactive oxygen species (ROS) in human brain microvascular endothelial cells (HBMVECs). In addition, Ramelteon displayed a robust anti-inflammatory capacity against isoflurane-induced insults and inflammation by reducing the generation of interleukin-1β (IL-1β), transforming growth factor-β (TGF-β), monocyte chemotactic protein 1 (MCP-1), stromal cell-derived factor-1 (SDF-1), matrix metalloproteinase-2 (MMP-2), and MMP-9. Furthermore, Ramelteon reduced the expression of cell adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) and E-selectin. Importantly, Ramelteon downregulated the activation of the p38MAPK/NF-κB signaling pathway, which is the key transcriptional regulator in the inflammation process. Our findings in the present study provide new evidence for the use of Ramelteon in the prevention of isoflurane-induced insults in brain endothelial cells.<br /><br /> Oropharynx squamous cell carcinoma (OPSCC) is a subtype of head and neck squamous cell carcinoma (HNSCC) arising from the base of the tongue, lingual tonsils, tonsils, oropharynx or pharynx. The majority of HPV-positive OPSCCs has a good prognosis, but a fraction of them has a poor prognosis, similar to HPV-negative OPSCCs. An in-depth understanding of the molecular mechanisms underlying OPSCC is mandatory for the identification of novel prognostic biomarkers and/or novel therapeutic targets.<br /><br /> 14 HPV-positive and 15 HPV-negative OPSCCs with 5-year follow-up information were subjected to gene expression profiling and, subsequently, compared to three extensive published OPSCC cohorts to define robust biomarkers for HPV-negative lesions. Validation of Aldo-keto-reductases 1C3 (AKR1C3) by qRT-PCR was carried out on an independent cohort (n = 111) of OPSCC cases. In addition, OPSCC cell lines Fadu and Cal-27 were treated with Cisplatin and/or specific AKR1C3 inhibitors to assess their (combined) therapeutic effects.<br /><br /> Gene set enrichment analysis (GSEA)on the four datasets revealed that the genes down-regulated in HPV-negative samples were mainly involved in immune system, whereas those up-regulated mainly in glutathione derivative biosynthetic and xenobiotic metabolic processes. A panel of 30 robust HPV-associated transcripts was identified, with AKR1C3 as top-overexpressed transcript in HPV-negative samples. AKR1C3 expression in 111 independent OPSCC cases positively correlated with a worse survival, both in the entire cohort and in HPV-positive samples. Pretreatment with a selective AKR1C3 inhibitor potentiated the effect of Cisplatin in OPSCC cells exhibiting higher basal AKR1C3 expression levels.<br /><br /> We identified AKR1C3 as a potential prognostic biomarker in OPSCC and as a potential drug target whose inhibition can potentiate the effect of Cisplatin.<br /><br />We identified AKR1C3 as a potential prognostic biomarker in OPSCC and as a potential drug target whose inhibition can potentiate the effect of Cisplatin.<br /><br /> Immune checkpoint inhibitors (ICIs) plus chemotherapy (CT) have strikingly expanded the therapeutic landscape for advanced non-small cell lung cancer (NSCLC), but little is known about which is superior. We performed a meta-analysis that compared the efficacy and safety of PD-1 inhibitor + CT with PD-L1 inhibitor + CT.<br /><br /> PubMed, Embase, Web of Science, Cochrane Library, and major international scientific meetings were searched for relevant randomized controlled trials (RCTs), and the indirect analysis was performed for PD-1 + CT vs PD-L1 + CT. The outcomes included progression-free survival (PFS), overall survival (OS), objective response rate (ORR) and treatment-related adverse events (TRAEs).<br /><br /> 8 phase III RCTs with 4253 patients comparing PD-1/PD-L1 + CT in NSCLC were included. The PD-1 + CT led to notably longer OS most in low/negative expression of PD-L1 for NSCLC patients compared with PD-L1 + CT. In terms of Grade 3-5 TRAEs, the results showed that PD-1 + CT and PD-L1 + CT exclusively increased the risk of adverse incidence than CT alone, especially for PD-L1 + CT (p &lt; 0.