AbstractThe study aimed to purify and characterize antioxidant peptides from chicken blood hemoglobin hydrolysate. The fraction M2 (< 3 KDa) with the strongest antioxidant activity was isolated by ultrafiltration, and its DPPH (1,1‐diphenyl‐2‐picryl‐hydrazyl radical) free radical scavenging rate, ABTS [2,2′‐Azinobis‐(3‐ethylbenzthiazoline‐6‐sulphonate)] free radical scavenging rate, and iron ion chelation activity were 82.91%, 77.49%, and 80.99%, respectively. After in vitro digestion, the antioxidant capacity of chicken blood hydrolysate was significantly higher than that before digestion (p < 0.05). M2 exhibited the strongest antioxidant activity after stomach digestion, with a DPPH radical scavenging rate and iron ion chelating power of 82.91% and 79.61%, respectively. Component A was purified from M2 by Sephadex G‐25 gel chromatography. The peptide sequences were identified by LC‐MS/MS from fraction A, and four peptides, AEDKKLIQ (944.54 Da), APAPAAK (625.36 Da), LSDLHAHKL (1033.57 Da), and LSNLHAYNL (1044.54 Da) were synthesized using the solid‐phase peptide method, among which APAPAAK was a novel antioxidant peptide. Molecular docking was used to simulate the binding of these four peptides to the key active site of Keap1 via hydrogen bonding. This study suggests that chicken blood may provide a new natural source of antioxidant peptides.

01 Jun 2022·European Journal of CancerQ1 · MEDICINE

Impact of trough concentrations of regorafenib and its major metabolites M-2 and M-5 on overall survival of chemorefractory metastatic colorectal cancer patients: Results from a multicentre GERCOR TEXCAN phase II study

Q1 · MEDICINE

Article

Author: Rousseau, Benoit ; Cohen, Romain ; Louvet, Christophe ; Andre, Thierry ; Hulin, Anne ; Bachet, Jean-Baptiste ; Boukerma, Arezki K ; Vernerey, Dewi ; Lucidarme, Olivier ; Tournigand, Christophe ; Chibaudel, Benoist ; Borg, Christophe ; Kim, Stefano ; Mazard, Thibault ; Henriques, Julie

PURPOSEThis prospective pharmacokinetic (PK) ancillary study of the TEXCAN phase II GERCOR trial of patients with chemorefractory metastatic colorectal cancer and treated with regorafenib (REGO) investigated correlations between overall survival (OS) and concentrations (C) of REGO and its active metabolites, M-2 and M-5.METHODS55 patients received REGO 160 mg/day for 21 days of a 28-day cycle (NCT02699073). REGO, M-2, M-5 were measured by liquid chromatography-mass spectrometry assay on day 15 of cycle 1 (C1) and 2 (C2). We studied the association between OS and Cmin of REGO, M-2 and M-5 at C1 and their accumulations between C1 and C2.RESULTSMedians of C2/C1 M-2 and M-5 ratios were 0.82 (interquartile range 0.50-1.78) and 0.75 (interquartile range 0.41-1.93), respectively. Patients with C2/C1 M-2 ratio ≥ median had improved survival compared to those < median (12.6 versus 4.0 months, P = 0.023), corresponding to a 66% mortality risk reduction in multivariate analysis. The C2/C1 M-2 ratio correlated with C1 REGO+M-2+M-5 (Csum; P = 0.006). Restricted cubic spline analysis showed an increased OS benefit as the C2/C1 M-2 ratio raises and when C1 Csum ranged between 2.5 and 5.5 mg/L. Patients within the Csum range had a reduced incidence of serious adverse events and improved OS.CONCLUSIONSWe identified PK parameters associated with a survival benefit in patients with metastatic colorectal cancer treated by REGO. OS and safety were favourable when C1 REGO+M-2+M-5 Csum ranged between 2.5 and 5.5 mg/L. These results pave the way for individual REGO dose modification strategies based on PK monitoring.CLINICAL TRIAL REFERENCENCT02699073.

01 May 2022·Archives of MicrobiologyQ4 · BIOLOGY

Bacillus subtilis suppresses the charcoal rot disease by inducing defence responses and physiological attributes in soybean

Q4 · BIOLOGY

Article

Author: Rajput, Laxman Singh ; Giri, Ved Prakash ; Singh, Satyendra Pratap ; Chauhan, Priyanka ; Gupta, Sateesh Chandra ; Dwivedi, Ashish ; Verma, Pratibha ; Bhattacharya, Arpita ; Mishra, Aradhana

Endophytes can induce the defence responses and modulates physiological attributes in host plants during pathogen attacks. In the present study, 127 bacterial endophytes (BEs) were isolated from different parts of healthy soybean plant. Among them, two BEs (M-2 and M-4) resulted a significant antagonistic property against Macrophomina phaseolina, causes charcoal rot disease in soybean. The antagonistic potential was evaluated through dual culture plate assay, where M-4 expressed higher antifungal activity than M-2 against M. phaseolina. The M-4 produces cell wall degrading enzymes viz. cellulase (145.71 ± 1.34 μgmL^-1), chitinase (0.168 ± 0.0009 unitmL^-1) and β,1-3 endoglucanase (162.14 ± 2.5 μgmL^-1), which helps in cell wall disintegration of pathogens. Additionally, M-4 also can produce siderophores, indole-3-acetic acid (IAA) (17.03 ± 1.10 μgmL^-1) and had a phosphate solubilization potential (19.89 ± 0.26 μgmL^-1). Further, GC-MS profiling of M-4 has been carried out to demonstrate the production of lipophilic secondary metabolites which efficiently suppress the M. phaseolina defensive compounds under co-culture conditions. Bio-efficacy study of M-4 strain shown a significant reduction in disease incidence around 60 and 80% in resistant and susceptible varieties of soybean, respectively. The inoculation of M-4 potentially enhances the physiological attributes and triggers various defence responsive enzymes viz. superoxide dismutase (SOD), phenol peroxidase (PPO), peroxidase (PO) and catalase (CAT). The histopathological study also confirmed that M-4 can reduce the persistence of microsclerotia in root and shoot tissue. Conclusively, M-4 revealed as an efficient biocontrol agent that can uses multifaceted measures for charcoal rot disease management, by suppress the M. phaseolina infection and enhance the physiological attributes of soybean.

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Indication	Highest Phase	Country/Location	Organization	Date
Glioma	Preclinical	US	Greenfire Bio LLCStartup	11 Apr 2024
Glioma	Preclinical	US	MGFB Bio	11 Apr 2024

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