Purification, identification and molecular docking of dual-functional peptides derived from corn protein hydrolysates with antioxidant and antiadhesive activity against Helicobacter pylori.

BACKGROUND: More than 50% of the world's population is infected with Helicobacter pylori, which is classified as a group I carcinogen by the World Health Organization (WHO). RESULTS: Corn protein dual-functional peptides were identified and functionally analyzed in vitro and in silico. Two novel dual-functional peptides were identified as Cys-Gln-Asp-Val-Pro-Leu-Leu (CQDVPLL, CQ7) and Thr-Ile-Phe-Pro-Gln-Cys (TIFPQC, TI6) using nanoscale liquid chromatography coupled to tandem mass spectrometry (nano-LC-MS/MS). The antiadhesive effects against H. pylori of CQ7 and TI6 were 45.17 ± 2.41% and 48.62 ± 1.84% at 4 mg mL-1 , respectively. In silico prediction showed that CQ7 and TI6 had good physicochemical properties. Molecular docking demonstrated that CQ7 and TI6 could bind to the adhesins BabA and SabA by hydrophobic interactions and hydrogen bonds, preventing H. pylori infection. Moreover, CQ7 showed strong antioxidant activity due to its unique amino acid composition. CONCLUSION: The present study demonstrated that the identified peptides, CQ7 and TI6, possess antioxidant and antiadhesive effects, preventing H. pylori infection and alleviating oxidative injury to the gastric mucosa. © 2023 Society of Chemical Industry.

Connectivity of the insular subdivisions differentiates posttraumatic headache-associated from nonheadache-associated mild traumatic brain injury: an arterial spin labelling study.

OBJECTIVE: The insula is an important part of the posttraumatic headache (PTH) attributed to mild traumatic brain injury (mTBI) neuropathological activity pattern. It is composed of functionally different subdivisions and each of which plays different role in PTH neuropathology. METHODS: Ninety-four mTBI patients were included in this study. Based on perfusion imaging data obtained from arterial spin labelling (ASL) perfusion magnetic resonance imaging (MRI), this study evaluated the insular subregion perfusion-based functional connectivity (FC) and its correlation with clinical characteristic parameters in patients with PTH after mTBI and non-headache mTBI patients. RESULTS: The insular subregions of mTBI + PTH (mTBI patients with PTH) and mTBI-PTH (mTBI patients without PTH) group had positive perfusion-based functional connections with other insular nuclei and adjacent discrete cortical regions. Compared with mTBI-PTH group, significantly increased resting-state perfusion-based FC between the anterior insula (AI) and middle cingulate cortex (MCC)/Rolandic operculum (ROL), between posterior insula (PI) and supplementary motor area (SMA), and decreased perfusion-based FC between PI and thalamus were found in mTBI + PTH group. Changes in the perfusion-based FC of the left posterior insula/dorsal anterior insula with the thalamus/MCC were significant correlated with headache characteristics. CONCLUSIONS: Our findings provide new ASL-based evidence for changes in the perfusion-based FC of the insular subregion in PTH patients attributed to mTBI and the association with headache features, revealing the possibility of potential neuroplasticity after PTH. These findings may contribute to early diagnosis of the disease and follow-up of disease progression.

Radiomics Analysis of Diffusion-Weighted Imaging and Long-Term Unfavorable Outcomes Risk for Acute Stroke.

BACKGROUND: Diffusion-weighted imaging radiomics could be used as prognostic biomarkers in acute ischemic stroke. We aimed to identify a clinical and diffusion-weighted imaging radiomics model for individual unfavorable outcomes risk assessment in acute ischemic stroke. METHODS: A total of 1716 patients with acute ischemic stroke from 2 centers were divided into a training cohort and a validation cohort. Patient outcomes were measured with the modified Rankin Scale score. An unfavorable outcome was defined as a modified Rankin Scale score greater than 2. The primary end point was all-cause mortality or outcomes 1 year after stroke. The MRI-DRAGON score was calculated based on previous publications. We extracted and selected the infarct features on diffusion-weighted imaging to construct a radiomic signature. The clinic-radiomics signature was built by measuring the Cox proportional risk regression score (CrrScore) and compared with the MRI-DRAGON score and the ClinicScore. CrrScore model performance was estimated by 1-year unfavorable outcomes prediction. RESULTS: A high radiomic signature predicted a higher probability of unfavorable outcomes than a low radiomic signature in the training (hazard ratio, 3.19 [95% CI, 2.51-4.05]; P<0.0001) and validation (hazard ratio, 3.25 [95% CI, 2.20-4.80]; P<0.0001) cohorts. The diffusion-weighted imaging Alberta Stroke Program Early CT Score, age, glucose level before therapy, National Institutes of Health Stroke Scale score on admission, glycated hemoglobin' radiomic signature, hemorrhagic infarction, and malignant cerebral edema were associated with an unfavorable outcomes risk after multivariable adjustment. A CrrScore nomogram was developed to predict outcomes and had the best performance in the training (area under the curve, 0.862) and validation cohorts (area under the curve, 0.858). The CrrScore model time-dependent areas under the curve of the probability of unfavorable outcomes at 1 year in the training and validation cohorts were 0.811 and 0.801, respectively. CONCLUSIONS: The CrrScore model allows the accurate prediction of patients with acute ischemic stroke outcomes and can potentially guide rehabilitation therapies for patients with different risks of unfavorable outcomes.

Altered amygdala effective connectivity in migraine without aura: evidence from resting-state fMRI with Granger causality analysis.

BACKGROUND: Granger causality analysis (GCA) has been used to investigate the pathophysiology of migraine. Amygdala plays a key role in pain modulation of migraine attack. However, the detailed neuromechanism remained to be elucidated. We applied GCA to explore the amygdala-based directional effective connectivity in migraine without aura (MwoA) and to determine the relation with clinical characteristics. METHODS: Forty-five MwoA patients and forty age-, sex-, and years of education-matched healthy controls(HCs) underwent resting-state functional magnetic resonance imaging (fMRI). Bilateral amygdala were used as seed regions in GCA to investigate directional effective connectivity and relation with migraine duration or attack frequency. RESULTS: MwoA patients showed significantly decreased effective connectivity from right amygdala to right superior temporal gyrus, left superior temporal gyrus and right precentral gyrus compared with HCs. Furthermore, MwoA patients demonstrated significantly decreased effective connectivity from the left amygdala to the ipsilateral superior temporal gyrus. Also, MwoA patients showed enhanced effective connectivity from left inferior frontal gyrus to left amygdala. Effective connectivity outflow from right amygdala to right precentral gyrus was negatively correlated to disease duration. CONCLUSIONS: Altered directional effective connectivity of amygdala demonstrated that neurolimbic pain networks contribute to multisensory integration abnormalities and deficits in pain modulation of MwoA patients.

Assessment of normalized cerebral blood flow and its connectivity with migraines without aura during interictal periods by arterial spin labeling.

BACKGROUND: Migraine constitutes a global health burden, and its pathophysiology is not well-understood; research evaluating cerebral perfusion and altered blood flow between brain areas using non-invasive imaging techniques, such as arterial spin labeling, have been scarce. This study aimed to assess cerebral blood flow (CBF) and its connectivity of migraine. METHODS: This study enrolled 40 patients with episodic migraine without aura (MwoA), as well as 42 healthy patients as control (HC). Two groups of normalized CBF and CBF connectivity were compared, and the relationship between CBF variation and clinical scale assessment was further evaluated. RESULTS: In comparison to HC subjects, MwoA patients exhibited higher CBF in the right middle frontal orbital gyrus (ORBmid.R) and the right middle frontal gyrus, while that in Vermis_6 declined. The increased CBF of ORBmid.R was positively correlated with both the Visual Light Sensitivity Questionnaire-8 (VLSQ-8) and the monthly attack frequency score. In MwoA, significantly decreased CBF connectivity was detected between ORBmid.R and the left superior frontal gyrus, the right putamen, the right caudate, as well as the right angular gyrus. In addition, increased CBF connectivity was observed between the left calcarine cortex and ORBmid.R. CONCLUSIONS: Our results indicate that migraine patients exhibit abnormalities in regional CBF and feature CBF connection defects at the resting state. The affected areas involve information perception, information integration, and emotional, pain and visual processing. Our findings might provide important clues for the pathophysiology of migraine.

Altered lateral geniculate nucleus functional connectivity in migraine without aura: a resting-state functional MRI study.

OBJECTIVES: To investigate the structural and functional connectivity changes of lateral geniculate nucleus (LGN) and their relationships with clinical characteristics in patients without aura. METHODS: Conventional MRI, 3D structure images and resting state functional MRI were performed in 30 migraine patients without aura (MwoA) and 22 healthy controls (HC). The lateral geniculate nucleus volumes and the functional connectivity (FC) of bilateral lateral geniculate nucleus were computed and compared between groups. RESULTS: The lateral geniculate nucleus volumes in patient groups did not differ from the controls. The brain regions with increased FC of the left LGN mainly located in the left cerebellum and right lingual gyrus in MwoA compared with HC. The increased FC of right LGN located in left inferior frontal gyrus in MwoA compared with HC. The correlation analysis showed a positive correlation between VLSQ-8 score and the increased FC of left cerebellum and right lingual gyrus. CONCLUSIONS: Photophobia in MwoA could be mediated by abnormal resting state functional connectivity in visual processing regions, the pain perception regulatory network and emotion regulation network. This result is valuable to further understanding about the clinical manifestation and pathogenesis of migraine.

Altered functional connectivity of the red nucleus and substantia nigra in migraine without aura.

BACKGROUND: Functional connectivity (FC) has been used to investigate the pathophysiology of migraine. Accumulating evidence is pointing toward malfunctioning of brainstem structures, i.e., the red nucleus (RN) and substantia nigra (SN), as an important factor in migraine without aura (MwoA). We aimed to identify atypical FC between the RN and SN and other brain areas in patients with MwoA and to explore the association between RN and SN connectivity changes and performance on neuropsychological tests in these patients. METHODS: Resting-state functional magnetic resonance imaging (fMRI) data were obtained from 30 patients with MwoA and 22 age-, sex-, and years of education-matched healthy controls (HC). The FC of the brainstem structures was analyzed using a standard seed-based whole-brain correlation method. The results of the brainstem structure FC were assessed for correlations with other clinical features. RESULTS: Patients with MwoA exhibited reduced left RN-based FC with the left middle frontal gyrus, reduced right RN-based FC with the ipsilateral superior parietal lobe, and increased FC with the ipsilateral cerebellum. Additionally, patients with MwoA demonstrated significantly decreased right SN-based FC with the right postcentral gyrus, left parietal lobule, and left superior frontal gyrus. Hypo-connectivity between the right SN and right postcentral gyrus was negatively correlated with disease duration (r = - 0.506, P = 0.004). Additionally, increased connectivity of the right RN to the ipsilateral cerebellar lobes was positively correlated with the Headache Impact Test-6 scores (r = 0.437, P = 0.016). CONCLUSIONS: The present study suggested that patients with MwoA have disruption in their RN and SN resting-state networks, which are associated with specific clinical characteristics. The changes focus on the regions associated with cognitive evaluation, multisensory integration, and modulation of perception and pain, which may be associated with migraine production, feedback, and development. Taken together, these results may improve our understanding of the neuropathological mechanism of migraine.

Four novel anti-adhesive activity peptides against Helicobacter pylori derived from rice bran protein: release, identification and anti-adhesive mechanisms elucidation.

H. pylori is a highly pathogenic and prevalent pathogen that is a class I carcinogen. More than 50% of the world's population is infected with H. pylori. An anti-adhesive strategy is an effective way to antagonize H. pylori infection, which does not cause H. pylori resistance and is safer compared to antibiotic therapy. In the present study, to obtain rice bran protein-derived anti-adhesive activity peptides against H. pylori, an efficient enzymatic hydrolysis system was established, and it was found that rice bran protein hydrolysate prepared under specific conditions possessed anti-adhesive activity against H. pylori. The anti-adhesive activity of rice bran protein hydrolysate (RPH) was 43.74 ± 1.12% (4 mg mL-1), and gastric digestion (RPHA) had no significant effect on its activity. Hydrophobic amino acids and aromatic amino acids were important for its anti-adhesive activity. Further, 284 peptide sequences with potential anti-adhesive activity were isolated and identified from RPHA. Combined with molecular docking results, four novel anti-adhesive activity peptides were finally screened, namely LS5 (LSFRL), SN8 (SNTPGMVY), VV7 (VVNFGNL) and PV9 (PVLWGVPKG). Among them, PV9 showed the highest anti-adhesive activity of 59.64 ± 2.00% (4 mg mL-1). These four peptides could bind H. pylori adhesins BabA and SabA, occupying the binding sites of cell receptors and acting as anti-adhesion agents. In conclusion, four rice bran protein-derived anti-adhesive activity peptides against H. pylori can be used for the development of novel functional foods antagonizing H. pylori infection.

Preparation of Corn Peptides with Anti-Adhesive Activity and Its Functionality to Alleviate Gastric Injury Induced by Helicobacter pylori Infection In Vivo.

More than 50% of the world population is infected with Helicobacter pylori (H. pylori), which is classified as group I carcinogen by the WHO. H. pylori surface adhesins specifically recognize gastric mucosal epithelial cells' (GES-1 cells) receptor to complete the adhesion. Blocking the adhesion with an anti-adhesion compound is an effective way to prevent H. pylori infection. The present study found that corn protein hydrolysate, hydrolyzed by Neutral, effectively alleviated gastric injury induced by H. pylori infection through anti-adhesive and anti-inflammatory effects in vitro and in vivo. The hydrolysate inhibited H. pylori adhesion to GES-1 cells significantly, and its anti-adhesive activity was 50.44 ± 0.27% at 4 mg/mL, which indicated that the hydrolysate possessed a similar structure to the GES-1 cells' receptor, and exhibited anti-adhesive activity in binding to H. pylori. In vivo, compared with the H. pylori infection model group, the medium and high dose of the hydrolysate (400-600 mg/kg·bw) significantly decreased (p < 0.05) the amount of H. pylori colonization, pro-inflammatory cytokines (IL-6, IL-1ß, TNF-α and MPO), chemokines (KC and MCP-1) as well as key metabolites of NF-κB signaling pathway levels (TLR4, MyD88 and NF-κB), and it increased antioxidant enzyme contents (SOD and GSH-Px) and the mitigation of H. pylori-induced pathological changes in the gastric mucosa. Taken together, these results indicated that the hydrolysate intervention can prevent H. pylori-induced gastric injury by anti-adhesive activity and inhibiting the NF-κB signaling pathway's induction of inflammation. Hence, the corn protein hydrolysate might act as a potential anti-adhesive agent to prevent H. pylori infection.