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While obtaining such data in vivo is not possible, these in vitro data show proof of concept for likely significant cell- and progestogen-specific PR-B effects.Central administration of L-arginine was reported to attenuate stress responses in neonatal chicks. The present study aimed to elucidate the differential effects of centrally administered L-arginine and its enantiomer, D-arginine, on the stress response in chicks and the associated mechanisms. Intracerebroventricular injection of L-arginine attenuated acute isolation stress by inducing sleep-like behavior, while central administration of D-arginine potentiated the stress response, reducing the time spent standing motionless with eyes open and increasing distress vocalizations compared to the control. The brain concentrations of amino acids and monoamines following L- and D-arginine administration during stress were also determined. L-Arginine significantly increased the mesencephalic L-glutamine concentration. D-Arginine administration did not affect the levels of L-arginine or other amino acids in the examined brain regions. 3,4-Dihydroxyphenylacetic acid (DOPAC) level and dopamine (DA) metabolic rate (DOPAC/DA) were significantly higher in the diencephalon in the D-arginine group compared to the L-arginine group, while the mesencephalic DA level was significantly lower in the D-arginine group compared to the control. In vitro experiment using the brain slice culture demonstrated that extracellular perfusion of D-arginine significantly elevated the mRNA expression level of monoamine oxidase B, the major enzyme involved in DA metabolism, in the locus coeruleus region of the brainstem. In conclusion, in neonatal chicks, central administration of D-arginine exerted a stimulant effect on the stress response, in contrast to the stress-attenuating effects of L-arginine, partly through an effect on brain dopaminergic metabolism and not through competition with the L-stereoisomer.Cell-penetrating peptides (CPPs) can deliver payloads into cells by forming complexes with bioactive molecules via either covalent or non-covalent bonds. Previously, we reported polyhistidine (H16 peptide HHHHHHHHHHHHHHHH-NH2) as a new CPP. This peptide is anticipated to be a valuable new carrier for drug delivery to intracellular lysosomes; the peptide can transport macromolecules into these organelles. In the present study, we examined the application of the H16 peptide as a drug delivery system (DDS) to reverse to lysosomal storage disease (LSD) in cells in vitro. LSDs are metabolic disorders caused by the loss of specific lysosomal enzymes. The majority of lysosomal enzymes are acidic proteins and we utilized this common feature for our DDS. Filgotinib We synthesized a polylysine-polyhistidine fusion peptide (K10H16 peptide KKKKKKKKKKGHHHHHHHHHHHHHHHH-NH2) and developed a simple method for transporting acidic proteins into intracellular lysosomes via formation of complexes of enzymes with the K10H16 peptide by electrostatic interaction. First, we demonstrated our strategy using maltose-binding protein-fused green fluorescent protein (MBP-GFP) to model an acidic protein. The K10H16 peptide bound to MBP-GFP and transported it into intracellular lysosomes. Further, alpha-galactosidase A (GLA), one of the lysosomal enzymes associated with LSD, was also delivered to intracellular lysosomes by the peptide. The complex between K10H16 peptide and GLA restored typical proliferation to LSD cells, which otherwise grew more slowly than normal cells. These results suggest that K10H16 peptide replenished lysosomal enzyme deficiency in LSD cells. The K10H16 peptide may be useful as a DDS for LSD therapy.Hepatocellular Carcinoma (HCC) is the main histological subtype of liver malignancy with poor prognosis. A growing body of evidence showed that Circular RNAs (circRNAs) are related to HCC tumorigenesis and progression. In this study, we investigated the function and regulation of circ-0038718 in HCC. We found that circ-0038718 was frequently elevated in HCC specimens and cell lines. High expression levels of circ-0038718 were correlated with unfavorable prognosis in HCC patients. Furthermore, we demonstrated that knockdown of circ-0038718 attenuated HCC cell proliferation and metastatic abilities, while overexpression of circ-0038718 resulted the converse effect. Silencing circ-0038717 inhibited HCC xenograft tumor development in vivo. Mechanistically, circ-0038718 acted as the sponge of tumor-suppressive miR-139-3p to regulate HCC progression. Rescue experiments suggested the oncogenic activity of circ-0038718 was partially exerted via modulating miR-139-3p expression. Inhibition of miR-139-3p abrogated the regulatory effect of circ-0038718 in HCC cells. In summary, our results unveiled that circ-0038718 could serve as an crucial regulator of HCC progression and provide a potential therapeutic target for HCC treatment.JC polyomavirus (JCPyV) causes progressive multifocal leukoencephalopathy (PML), a demyelinating disease of the central nervous system, in immunocompromised patients. Although PML used to be rare, recently the incidence of PML has risen due to an increase in immunosuppressive therapy. An in vitro JCPyV infection system could be used for anti-drug screening and investigation of tropism changes, but study of JCPyV in vitro has been limited due to the difficulty of efficiently propagating the virus in cultured cells. PML-type JCPyV efficiently propagates in primary human fetal and progenitor cell-derived astrocytes, but the preparation of cells from human fetuses is associated with severe ethical problems. In this study, human iPS cell-derived astrocytes were exposed to PML-type JCPyV. Infection, replication, and VP1 and T antigens of JCPyV were detected and confirmed in this culture. The non-coding control region (NCCR) of M1-IMRb was conserved in infected cells without point mutations. In addition, PML-type JCPyV genomic DNA in infected cells was detected as a single band of approximately 5.1 kbp, with no deletions. This is the first demonstration that human iPS cell-derived astrocytes efficiently support replication of PML-type JCPyV without production of defective interfering particles. These findings indicated that a culture system using human iPS cell-derived astrocyte would be useful for studies of PML, especially for screening anti-JCPyV drugs.