GS-9688 (selgantolimod) is an oral selective small molecule agonist of toll-like receptor 8 (TLR8) in clinical development for the treatment of chronic hepatitis B (CHB). In this study, we evaluated the antiviral efficacy of GS-9688 in woodchucks chronically infected with woodchuck hepatitis virus (WHV), a hepadnavirus closely related to hepatitis B virus (HBV). WHV-infected woodchucks received eight weekly oral doses of vehicle, 1 mg/kg GS-9688 or 3 mg/kg GS-9688. Vehicle and 1 mg/kg GS-9688 had no antiviral effect, whereas 3 mg/kg GS-9688 induced a >5 log 10 reduction in serum viral load and reduced WHV surface antigen (WHsAg) levels to below the limit of detection in half of the treated woodchucks. In these animals, the antiviral response was maintained until the end of the study (>5 months after the end of treatment). GS-9688 treatment reduced intrahepatic WHV RNA and DNA levels by >95% in animals in which the antiviral response was sustained after treatment cessation, and these woodchucks also developed detectable anti-WHsAg antibodies. The antiviral efficacy of weekly oral dosing with 3 mg/kg GS-9688 was confirmed in a second woodchuck study. The antiviral response to GS-9688 did not correlate with systemic GS-9688 or cytokine levels but was associated with transient elevation of liver injury biomarkers and enhanced proliferative response of peripheral blood mononuclear cells (PBMC) to WHV peptides. Transcriptomic analysis of liver biopsies taken prior to treatment suggested that T follicular helper cells (T FH) and various other immune cell subsets may play a role in the antiviral response to GS-9688. Conclusion: Finite, short-duration treatment with a clinically relevant dose of GS-9688 is well tolerated and can induce a sustained antiviral response in WHV-infected woodchucks. The identification of a baseline intrahepatic transcriptional signature associated with response to GS-9688 treatment provides insights into the immune mechanisms that mediate this antiviral effect. Approximately 260 million individuals are chronically infected with hepatitis B virus (HBV), and over half a million people are estimated to die each year due to liver diseases associated with chronic hepatitis B (CHB), such as cirrhosis and hepatocellular carcinoma (HCC). Immunological control of CHB ("functional cure") is defined as sustained loss of HBV surface antigen (HBsAg) off treatment, with or without seroconversion to anti-HBs antibody. Several nucleos(t)ide analogs, as well as interferon-alpha (IFN-α), are approved for the treatment of CHB. These therapies reduce viremia and

In order to isolate antioxidant peptides from oats globulin hydrolyzed alcalase, an antioxidant peptide was isolated and purified using ultra-filtration and ion-exchange chromatography. Hydroxyl and 1,1-diphenyl-2-pycrylhydrazyl (DPPH) radical scavenging capacity was analyzed to evaluate the antioxidant activity of peptide. Five fractions were obtained after ultra-filtration, fraction with molecular weight >10KDa showed the strongest hydroxyl and DPPH radical scavenging ability of 58.38 ± 0.87% and 24.53 ± 0.53% (p < 0.05). Fraction C which was purified via ionexchange chromatography, exhibited the maximum antioxidant activity (IC 50 of hydroxyl and DPPH radical scavenging ability was 1.83 ± 0.03 mg mL −1 and 4.11 ± 0.07 mg mL −1) among other fractions (p < 0.05). Subsequently, five antioxidant peptides were identified by electrospray ionization mass spectrometry (ESI-MS/MS), with the amino acid sequence of IRIPIL,

BACKGROUND: Peptide-Ca complexes can promote Ca absorption. The present study aimed to determine the transport mechanism and structural characteristics of sunflower seed and peanut peptides with high Ca binding capacity with respect to developing third-generation Ca supplements and functional food ingredients. RESULTS: High Ca-binding fractions of 1-3 kDa sunflower seed peptide (SSP 4) and ≥ 10 kDa peanut peptide (PP 1) had higher amount of Ca transported than CaCl 2 and two hydrolyzed proteins in Caco-2 cells. SSP 4 and PP 1 were separated by Ca ion metal chelate affinity chromatography, and high Ca-binding fractions were observed for SSP 4-P 2 and PP 1-P 2. The amino acid sequences of SSP 4-P 2 and PP 1-P 2 were characterized by high-performance liquid chromatography-electrospray ionization-time of flight mass spectrometry. Seven and eight peptides were identified from SSP 4-P 2 and PP 1-P 2 , respectively. These peptides had molecular weights ranging from 1500 Da to 2500 Da and a large number of characteristic amino acid sequences, such as EEEQQQ, EQ-QQQ-QQ, QQ-QQQQQ, E-EEE, EE-EEQ, RR, Q-QQ-QQQ, EE-EQ-EE-Q, QQ-QQQQ, and Q-QQQQ, where 'E' is glutamic acid and 'Q' is glutamine. CONCLUSION: SSP 4 and PP 1 can promote Ca transport in Caco-2 cells without affecting cell permeability. The amino acid sequences of SSP 4-P 2 and PP 1-P 2 with high Ca-binding abilities contain characteristic sequences, such as continuous glutamic acid and glutamine, and have low molecular weights.

SummaryHydrolysed proteins from sunflower seed and peanut were separated by ultrafiltration. Results showed that 1–3 kDa sunflower seed peptide (SSP4) and ≥10 kDa peanut peptide (PP1) fractions had the highest Ca‐binding capacity of 104.80 and 124.74 mg g−1, respectively. After Ca binding, scanning electron microscopy results showed that the loose sheet‐like structure of SSP4 and PP1 transformed into a granular structure. Fourier‐transform infrared spectroscopy results showed that carboxyl and amide groups were involved in Ca binding. Growing male mice were assigned to eight groups: control, CaCO3 and six experimental groups (low, medium and high doses for each SSP4‐Ca and PP1‐Ca). Apparent Ca absorption rate, bone mineral density (BMD), bone surface microstructure and biomechanical index and serum biochemical index were evaluated. Animal experiment results indicated that SSP4‐Ca and PP1‐Ca can improve Ca bioavailability; effectively enhance BMD and structure; and promote Ca absorption. The peptide–Ca complexes were absorbed better than CaCO3 and promoted Ca accumulation in the bone. PP1‐Ca was better than SSP4‐Ca in promoting calcium absorption and enhancing BMD.

Umami peptides were derived from enzymatic hydrolysis of sunflower seed protein, followed by isolation and identification. The flavourzyme-enzymatic hydrolysates exhibited the highest umami intensity value of 10.72 ± 0.05 and the lowest bitterness, when pH was adjusted to 7.0, the flavorzyme was added at enzyme-to-substrate (E/S) ratio of 1:25 (w/w), then incubated in a temperature-controlled water bath at 55°C, and the hydrolysis time was 480 min. Ultrafiltration, gel filtration chromatography, and reversed-phase high-performance liquid chromatography (RP-HPLC) were used to isolate the umami peptides of sunflower seed. Five fractions were obtained after ultra-filtration, fraction with molecular weight 1-3 kDa showed highest umami intensity value 13.93 ± 0.06. Fraction F1, which was purified via sephadex gel filtration chromatography, exhibited high umami value (12.21 ± 0.06), and low bitterness (4.57 ± 0.06). Seven sub-fractions were purified by RP-HPLC, and the umami taste value of F1-4 was the highest (14.16 ± 0.05), which was 1.32 times stronger than that of sunflower seed protein hydrolysates without any purification. Furthermore, the structure of fraction F1-4 was characterized by mass spectrometry, and three peptide fractions were identified, with amino acid sequences of DVNNPANQLD, NNENQLDEYQR, and EFEGGSIEH, respectively.Caracterización sensorial y estructural de los péptidos umami derivados de la semilla de girasol