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Synthesis of impurity reference compound of anti-tumor drug ISIS 183750 was achieved. In this process, a general method for synthesis of 2-deoxy ribosyl disaccharide nucleosides was established for the first time. [ABSTRACT FROM AUTHOR]

In mammals, oxidative stress-induced apoptosis of granulosa cells is one of the major causes of follicular atresia, affecting ovarian physiological function. Protegrin-1 (PG-1) is an antimicrobial peptide with effective antimicrobial activity, immunomodulatory function, and porcine growth-promoting effects. PG-1 has been detected in porcine ovaries follicles. This study aimed to investigate the effect of PG-1 on oxidative stress-induced apoptosis of porcine ovarian granulosa cells and the underlying molecular mechanism. Granulosa cells were obtained from porcine follicles and treated with H 2 O 2 to establish the oxidative stress model, and then treated with or without PG-1 (10 μg/mL). PG-1 significantly suppressed H 2 O 2 -induced apoptosis in granulosa cells after 24 h of treatment. Furthermore, these results revealed that PG-1 increased the mRNA and protein expression of anti-apoptotic B cell lymphoma/leukemia 2 (BCL2) and the BCL2/Bcl-2-associated X protein (BAX) ratio while decreasing the expression of pro-apoptotic BAX and active caspase-3. Using Western blot analysis, it was found that PG-1 decreased the phosphorylation of RNA-like endoplasmic reticulum kinase (PERK) and the α-subunit of eukaryotic initiation factor 2 (eIF2α) as well as the protein expression level of CCAAT enhancer-binding protein homologous protein (CHOP), all of which were increased by H 2 O 2. Moreover, inhibitors against PERK and phospho-eIF2ɑ both suppressed the H 2 O 2 -induced granulosa cells apoptosis and enhanced the anti-apoptosis effect of PG-1. Taken together, our findings demonstrated that PG-1 inhibited porcine ovarian granulosa cell apoptosis from oxidative stress via the PERK/eIF2α/CHOP signaling pathway in vitro , which suggests the novel regulatory function of the antimicrobial peptide in the ovary. • PG-1 significantly inhibited H 2 O 2 -induced apoptosis in porcine granulosa cells. • PG-1 significantly suppressed PERK/eIF2α/CHOP signaling pathway which was activated by H 2 O 2. • Inhibition of PERK/eIF2α signaling pathway enhanced the anti-apoptosis effect of PG-1 on porcine granulosa cells. [ABSTRACT FROM AUTHOR]

• Protegrin-1 promoted the viability of porcine granulosa cells. • Transcriptome analysis showed that PG1 regulate genes with GC and ovarian function. • PG1 downregulated many pro-inflammatory genes in porcine GCs. • PG1 may regulate ovarian function through its immunomodulatory activities. Protegrin-1 (PG1) is an antimicrobial peptide (AMP) that has garnered increasing attention due to its potent immune defense activity. Our previous studies demonstrated the ability of PG1 to enhance proliferation and inhibit apoptosis of porcine granulosa cells (GCs) under oxidative stress. GCs play a crucial role in ovary follicular development. However, the specific function and underlying mechanisms of AMP in follicular development still need further elucidation. The present study aimed to comprehensively explore the biological effects of PG1 on porcine GCs using transcriptome profiling by RNA sequencing technology. Isolated GCs were incubated with or without PG1 for 24 h and transcriptome-wide analysis was exerted to identify differentially expressed genes (DEGs). The results of expression analysis revealed 1,235 DEGs, including 242 up-regulated genes and 993 down-regulated genes (|log2 (FoldChange)| > 1; adjusted P -value < 0.05). The expression levels of 7 selected DEGs were validated by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) analysis, which was consistent with the RNA-sequencing data. Among the significant DEGs, several genes associated with GC function and ovarian follicle development were identified, such as estrogen receptor 2 (ESR2), growth and differentiation factor 6 (GDF6), cell division cycle 20 homolog (CDC20), Notch3 , ephrin and Eph receptor system, Egl nine homolog 3 (EGLN3), and BCL2 like 14 (BCL2L14). Gene Ontology (GO) analysis revealed that the top three significant GO terms were inflammatory response, defense response, and granulocyte migration. Additionally, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis presented that DEGs were mainly enriched in the immune system, infectious disease, signaling molecules and interaction, and immune disease. Furthermore, Ingenuity Pathway Analysis (IPA) predicted that the top activated pathway was Liver X Receptor (LXR)/ Retinoid X Receptor (RXR) Activation which is known to be associated with female reproduction. Predicted protein–protein interactions (PPIs) analysis identified complement C3 (C3) as the top node with the highest degree of network connection and revealed that DEGs in the sub-networks were involved in cytokine-cytokine receptor interaction, neuroactive ligand-receptor interaction, chemokine signaling pathway, and metabolic process. In conclusion, this study expanded the understanding of the effects of PG1 on porcine GCs at the transcriptomic level and provided a theoretical basis for further investigation into the role of PG1 in immune defense and mammalian ovarian follicular development. [ABSTRACT FROM AUTHOR]

Galactosyl and lactosyl conjugated 6A,6D-bifunctionlized β cyclodextrin derivatives were designed and synthesized as the potential liver cancer drug carriers through SN2 replacement and click reactions in order to increase liver cancer drug’s targeting ability, solubility and stability. The synthetic methods and strategies to obtain the designed compounds were discussed. [ABSTRACT FROM AUTHOR]

Combining advantageous sequences of Alchemia and Sanofi methods of synthesis of Fondaparinux, a more efficient and practical synthetic strategy for the synthesis of corresponding protected pentasaccharide was developed. The protected pentasaccharide was smoothly converted into Fondaparinux in overall high yield (1%). [ABSTRACT FROM AUTHOR]

We investigated the anti-inflammatory effect of trilobatin, the flavonoid isolated from the leaves of Lithocarpus polystachyus Rehd, as well as the underlying molecular mechanisms. Treatment with trilobatin (0.005-5μM) dose-dependently inhibited the lipopolysaccharide (LPS)-induced mRNA expression and secretion of pro-inflammatory cytokines, including tumor necrosis factor α (TNFα), interleukin-1β (IL-1β) and interleukin-6 (IL-6), in RAW 264.7 macrophages. However, no further inhibition was detected when the concentration of trilobatin was increased to 50μM. Western blot analysis confirmed that the mechanism of the anti-inflammatory effect was correlated with the inhibition of LPS-induced inhibitor of nuclear factor-kappa B α (IκBα) degradation and nuclear factor-kappa B (NF-κB) p65 phosphorylation. In addition, trilobatin also showed a significant inhibition of LPS-induced TNFα and IL-6 at both the mRNA and protein levels in a mouse model. Our results suggest that trilobatin potentially inhibits the LPS-induced inflammatory response by suppressing the NF-κB signaling pathway. [ABSTRACT FROM AUTHOR]