A novel gelatin composite film with melt extrusion for walnut oil packaging.

Gelatin have excellent film-forming and barrier properties, but its lack of biological activity limits its application in packaging. In this study, fish gelatin incorporated with apple polyphenol/cumin essential oil composite films were successfully prepared by melt extrusion. The cross-linking existed in gelatin and apple polyphenol improved the thermal stability and oxidation resistance of the film. The synergistic effect of apple polyphenols and cumin essential oil decreased the sensitivity of the film to water, especially the water solubility decreased from 41.60 % to 26.07 %. The plasticization of essential oil nearly doubled the elongation at break while maintaining the tensile strength of the film (11.45 MPa). Furthermore, the FG-CEO-AP film can inhibit peroxide value to extend the shelf life about 20 days in the walnut oil preservation. In summary, the apple polyphenol/cumin essential oil of FG film exhibits excellent comprehensive properties and high preparation efficiency for utilization as an active packaging material.

Identifying a Gene Deficiency in the Antiviral Innate Immune Signaling Pathway.

Innate immunity is an important defense barrier for the human body. After viral pathogen-associated molecular patterns (PAMPs) are detected by host-pathogen recognition receptors (PRRs), the associated signaling pathways trigger the activation of the interferon (IFN) regulatory factor (IRF) family members and the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). However, any gene defects among the signaling adaptors will compromise innate immune efficiency. Therefore, investigating genetic defects in the antiviral innate immune signaling pathway is important. We summarize the commonly used research methods related to antiviral immune gene defects and outline the relevant research protocols, which will help investigators study antiviral innate immunity.

Multispectral and molecular simulation of the interaction of human α1-acid glycoprotein with palbociclib.

Palbociclib, a selective CDK4/6 inhibitor with potent anti-tumor effects, was investigated for its interaction with human α1-acid glycoprotein (HAG). Spectral analysis revealed that palbociclib forms a ground state complex with HAG, exhibiting binding constant (Kb) of 104 M-1 at the used temperature range. The interaction between the two was determined to be driven mainly by hydrogen bonding and hydrophobic forces. Multispectral studies indicated that the bound palbociclib altered the secondary structure of HAG and reduced polarity around Trp and Tyr amino acids. And, molecular docking and dynamics simulations verified the experimental findings. Finally, most of the metal ions present in plasma, such as K+, Cu2+, Ca2+, Mg2+, Ni2+, Fe3+, and Co2+, are detrimental to the binding of palbociclib to HAG, with the exception of Zn2+, which is favorable.

Radiomics-based model for prediction of TGF-ß1 expression in head and neck squamous cell carcinoma.

OBJECTIVE: To explore the connection between TGF-ß1 expression and the survival of patients with head and neck squamous cell carcinoma (HNSCC), as well as whether non-invasive CT-based Radiomics can predict TGF-ß1 expression in HNSCC patients. METHODS: Data on transcriptional profiling and clinical information were acquired from the TCGA database and subsequently categorized based on the TGF-ß1 expression cutoff value. Based on the completeness of enhanced arterial phase CT scans, 139 HNSCC patients were selected. The PyRadiomics package was used to extract radiomic features, and the 3D Slicer software was used for image segmentation. Using the mRMR_RFE and Repeat LASSO algorithms, the optimal features for establishing the corresponding gradient enhancement prediction models were identified. RESULTS: A survival analysis was performed on 483 patients, who were divided into two groups based on the TGF-ß1 expression cut-off. The Kaplan-Meier curve indicated that TGF-ß1 was a significant independent risk factor that reduced patient survival. To construct gradient enhancement prediction models, we used the mRMR_RFE algorithm and the Repeat_LASSO algorithm to obtain two features (glrlm and ngtdm) and three radiation features (glrlm, first order_10percentile, and gldm). In both the training and validation cohorts, the two established models demonstrated strong predictive potential. Furthermore, there was no statistically significant difference in the calibration curve, DCA diagram, or AUC values between the mRMR_RFE_GBM model and the LASSO_GBM model, suggesting that both models fit well. CONCLUSION: Based on these findings, TGF-ß1 was shown to be significantly associated with a poor prognosis and to be a potential risk factor for HNSCC. Furthermore, by employing the mRMR_RFE_GBM and Repeat_LASSO_GBM models, we were able to effectively predict TGF-ß1 expression levels in HNSCC through non-invasive CT-based Radiomics.

A review on the in vitro and in vivo screening of α-glucosidase inhibitors.

As a global metabolic disease, the control and treatment of diabetes have always been the focus of medical research. α-Glucosidase is a key enzyme in regulating blood glucose levels and has important applications in the treatment of diabetes. This review aims to explore the enzyme activity of α-glucosidase and its inhibition mechanism and evaluate the efficacy and limitations of existing inhibitor screening methods. First, the chemical structure, biological activity, and influencing factors of α-glucosidase on diabetes are discussed in detail. Then, the various methods that have been used to screen α-glucosidase inhibitors in recent years are reviewed, including in vivo animal experiments, in vitro experiments, and virtual molecular docking. The experimental principles, advantages, and limitations of each method and their application in discovering new inhibitors are also discussed. Finally, this review emphasizes the importance of developing efficient and safe α-glucosidase inhibitors, summarizes the advantages and disadvantages of various screening models, and proposes future research directions. This review comprehensively examines the enzyme activity of α-glucosidase and the screening methods for α-glucosidase inhibitors, provides an important perspective in the field of diabetes drug discovery and development, and provides a reference for future research.

Dual role of exosomal circCMTM3 derived from GSCs in impeding degradation and promoting phosphorylation of STAT5A to facilitate vasculogenic mimicry formation in glioblastoma.

Background: Glioblastoma (GBM) is characterized by abundant neovascularization as an essential hallmark. Vasculogenic mimicry (VM) is a predominant pattern of GBM neovascularization. However, the biological functions of circRNAs prompting VM formation in GBM remains unclarified. Methods: The circular RNA circCMTM3 was identified through high-throughput sequencing and bioinformatics analysis. The expression of circCMTM3 in exosomes in glioma tissues and cells was verified via RT-qPCR and FISH. In vitro and in vivo assays, such as EdU, MTS, Transwell, and tube formation assays were performed to investigate functional roles of circCMTM3. Meanwhile, in situ tumorigenesis assay were implemented to explore the influences of circCMTM3 on the GBM progression. Additionally, RNA pull-down, RIP, ChIP, and dual-luciferase reporter gene assays were executed to confirm the underlying regulation mechanism of circCMTM3. Results: CircCMTM3, as a novel circular RNA, was packaged into exosomes derived from glioblastoma stem cells (GSCs), which facilitates the phenotypic transition of differentiated glioma cells (DGCs) to VM. Mechanistically, exosomal circCMTM3 is internalized by DGCs and disrupt the ubiquitination degradation of STAT5A and STAT5B by E3 ubiquitin ligase CNOT4. Additionally, through molecular scaffold function of circCMTM3, STAT5A is activated and triggers transcriptional regulation of target genes including the pro-vasculogenic factor CHI3L2 and the RNA-binding protein SRSF1. Subsequently, circCMTM3/STAT5A/SRSF1 positive feedback loop sustainably enhances VM formation and accelerates tumor progression in GBM. Conclusion: Exosomal circCMTM3 possessing growth factor-mimetic property activates the JAK2/STAT5A pathway via non-canonical manner, and promotes VM formation in GBM. The molecular communications between GSCs and DGCs offers a therapeutic strategy for targeting the neovascularization of GBM.

Fascin Inhibitor NP-G2-044 Decreases Cell Metastasis and Increases Overall Survival of Mice-Bearing Lung Cancers.

AIM: Fascin is an actin-binding protein that promotes tumor metastasis. The inhibition of fascin on the progress of non-small cell lung cancer (NSCLC) is not very clear. Hence, this study explored the potential effect of NP-G2-044, a novel fascin inhibitor, in human NSCLC lines and the Lewis lung cancer (LCC) mice model. METHODS: The growth of cells was analyzed via CCK-8 assays, and the flow cytometry was adopted for cell cycle and apoptosis analysis, as well as the migration and invasion of NSCLC cells with or without NP-G2-044. The therapy of NP-G2-044, which synergizes with cisplatin and PD-1, was evaluated in the established xenograft Lewis's lung cancer of mice. RESULTS: Fascin was overexpressed in human NSCLC cells, and inhibition of fascin by NP-G2-044 attenuated NSCLC cell growth and remarkably undermined the ability of migration and invasion in vitro, which was related to the reduced epithelialmesenchymal transition (EMT) including downregulation of N-cadherin and vimentin, and upregulation of E-cadherin. Further results implied that the above changes may be partially mediated by the Wnt/ß-catenin pathway. In vivo, NP-G2-044 slowed down tumor development and enhanced overall survival alone, leading to synergistic anticancer effects with cisplatin or PD-1 inhibitor. CONCLUSION: Fascin inhibition could inhibit the metastasis of NSCLC and has the potential to enhance the efficacy of cisplatin and PD-1 inhibitors by blocking the Wnt/ß- catenin pathway.

New progress in HBV control and the cascade of health care for people living with HBV in China: evidence from the fourth national serological survey, 2020.

Background: Since 1992, when recombinant hepatitis B vaccine was introduced in China, government health officials have used nationally representative serological surveys to monitor progress in prevention and control of hepatitis B. In 2020, we conducted the fourth seroepidemiological survey, which for the first time included medical evaluation of the clinical status of HBsAg positive subjects over the age of 15 and their medical management. We report survey results in comparison with the three previous surveys. Methods: Consistent with previous national surveys, the 2020 survey used a stratified, three-stage cluster random sampling method to select for evaluation 1-69-year-olds in 120 national disease surveillance points. Blood samples were tested for HBsAg, anti-HBV surface antigen (anti-HBs), and anti-HBV core antigen (anti-HBc) in the National Hepatitis Laboratory of the Institute for Viral Disease Control and Prevention of China CDC. HBsAg positive subjects aged ≥15-year were evaluated for evidence of liver disease, and through face-to-face questionnaire-based survey, we determined the healthcare management cascade of HBV-infected individuals. Findings: HBsAg prevalence in 1-69-year-olds was 5.86%; in children 1-4 years of age, seroprevalence was 0.30%; 75 million people were living with HBV nationwide. Among HBsAg-positive individuals 15 years and older, expert medical examination found that 78.03% were HBsAg carriers with no evidence of liver damage, 19.63% had chronic HBV with liver enzyme abnormalities, 0.84% had evidence of cirrhosis, and 0.15% had evidence of liver cancer. 59.78% of HBsAg + individuals were aware that they were positive before the survey, 30 million were unaware; 38.25% of those who knew they were positive (17 million) had medical indications for antiviral treatment, and 17.33% of these individuals (3 million) were being treated with antivirals. Interpretation: The decline in HBsAg prevalence in the general population, from 9.72% in 1992 to 5.86% in 2020, and in 1-4-year-olds from 9.67% in 1992 to 0.30% in 2020, shows progress that continues on track toward WHO targets for prevention of new infections. Implementation of acceptable strategies to identify infected individuals and offer long-term medical monitoring and management will be important to prevent complications from hepatitis B infection and for meeting WHO cascade-of-care targets. Funding: The study was funded by the Major Science and Technology Special Project of China's 13th 5-Year Plan (grant no. 2017ZX10105015); Central finance-operation of public health emergency response mechanism of Chinese Center for Disease Control and Prevention (131031001000200001, 102393220020010000017).

Characterization of additive gene-environment interactions for colorectal cancer risk.

BACKGROUND: Colorectal cancer (CRC) is a common, fatal cancer. Identifying subgroups who may benefit more from intervention is of critical public health importance. Previous studies have assessed multiplicative interaction between genetic risk scores and environmental factors, but few have assessed additive interaction, the relevant public health measure. METHODS: Using resources from colorectal cancer consortia including 45,247 CRC cases and 52,671 controls, we assessed multiplicative and additive interaction (relative excess risk due to interaction, RERI) using logistic regression between 13 harmonized environmental factors and genetic risk score including 141 variants associated with CRC risk. RESULTS: There was no evidence of multiplicative interaction between environmental factors and genetic risk score. There was additive interaction where, for individuals with high genetic susceptibility, either heavy drinking [RERI = 0.24, 95% confidence interval, CI, (0.13, 0.36)], ever smoking [0.11 (0.05, 0.16)], high BMI [female 0.09 (0.05, 0.13), male 0.10 (0.05, 0.14)], or high red meat intake [highest versus lowest quartile 0.18 (0.09, 0.27)] was associated with excess CRC risk greater than that for individuals with average genetic susceptibility. Conversely, we estimate those with high genetic susceptibility may benefit more from reducing CRC risk with aspirin/NSAID use [-0.16 (-0.20, -0.11)] or higher intake of fruit, fiber, or calcium [highest quartile versus lowest quartile -0.12 (-0.18, -0.050); -0.16 (-0.23, -0.09); -0.11 (-0.18, -0.05), respectively] than those with average genetic susceptibility. CONCLUSIONS: Additive interaction is important to assess for identifying subgroups who may benefit from intervention. The subgroups identified in this study may help inform precision CRC prevention.

Triptolide-induced acute liver injury and its mechanism with estradiol in regulating macrophage-mediated inflammation and hepatocyte function.

Triptolide (TP), a diterpene from Tripterygium wilfordii, exhibits potent anti-inflammatory, immunomodulatory, and antitumor properties but is limited by severe hepatotoxicity. This study investigates sex differences in TP-induced liver injury and the protective role of estradiol (E2) in modulating macrophage-mediated inflammation and hepatocyte function. An acute liver injury model was established in male and female Balb/c mice using intraperitoneal TP injection. Liver function tests, histological analyses, and immunohistochemical staining were performed. THP-1 macrophage and various liver cell lines were used to study the effects of TP and E2 in vitro. Virtual screening, molecular docking, luciferase assays, and qPCR were employed to identify potential targets and elucidate underlying mechanisms. TP caused more severe liver injury in female mice, evidenced by increased liver indices, aspartate aminotransferase (AST) levels, and extensive hepatocyte damage. TP promoted M1 macrophage polarization, enhancing inflammation, particularly in female mice. E2 mitigated TP-induced inflammatory responses by downregulating pro-inflammatory cytokines and macrophage activation markers. Molecular docking and functional assays identified Nuclear receptor subfamily 1 group I member 2 (NR1I2) as a key target mediating the protective effects of E2. The study highlights significant sex differences in TP-induced hepatotoxicity, with females being more susceptible. E2 exerts protective effects against TP-induced liver injury by modulating immune responses, presenting a potential therapeutic approach to mitigate drug-induced liver injury (DILI). Further research on NR1I2 could lead to targeted therapies for reducing drug-induced liver damage.

CXCR4 orchestrates the TOX-programmed exhausted phenotype of CD8+ T cells via JAK2/STAT3 pathway.

Evidence from clinical trials suggests that CXCR4 antagonists enhance immunotherapy effectiveness in several cancers. However, the specific mechanisms through which CXCR4 contributes to immune cell phenotypes are not fully understood. Here, we employed single-cell transcriptomic analysis and identified CXCR4 as a marker gene in T cells, with CD8+PD-1high exhausted T (Tex) cells exhibiting high CXCR4 expression. By blocking CXCR4, the Tex phenotype was attenuated in vivo. Mechanistically, CXCR4-blocking T cells mitigated the Tex phenotype by regulating the JAK2-STAT3 pathway. Single-cell RNA/TCR/ATAC-seq confirmed that Cxcr4-deficient CD8+ T cells epigenetically mitigated the transition from functional to exhausted phenotypes. Notably, clinical sample analysis revealed that CXCR4+CD8+ T cells showed higher expression in patients with a non-complete pathological response. Collectively, these findings demonstrate the mechanism by which CXCR4 orchestrates CD8+ Tex cells and provide a rationale for combining CXCR4 antagonists with immunotherapy in clinical trials.

Porto-Sinusoidal Vascular Disease: A New Nomenclature Different from Idiopathic Non-Cirrhotic Portal Hypertension.

BACKGROUND AND AIMS: Porto-sinusoidal vascular disease (PSVD) as a novel clinical conception was modified on the basis of idiopathic non-cirrhotic portal hypertension (INCPH). This study aimed to compare the clinical, biochemical histological features and prognosis between the diagnostic criteria for PSVD and that of INCPH. METHODS: A total of 65 patients who underwent liver biopsies were analyzed retrospectively. The clinical, pathological and prognosis date were reviewed and screened according to the latest diagnostic criteria of PSVD and INCPH. RESULTS: A total of 65 patients were diagnosed with PSVD, of which 31 (47.69%) also fulfilled INCPH criteria. Specific histological and specific clinical portal hypertension (PH) signs were found in 34 (52.31%) and 30 (46.15%) of the patients, respectively. PSVD patients showed higher LSM levels (11.45 (6.38, 18.08) vs. 7.90 (6.70, 13.00), p = 0.039) than the INCPH patients. INCPH patients had a higher cumulative incidence of liver-related complications than the PSVD patients (86.95% vs. 35.71%, log-rank p < 0.001). CONCLUSION: Novel PSVD criteria facilitate early diagnosis. PSVD patients with other liver diseases may have higher LSM values. Disease progression and survival outcomes are correlated with PH in PSVD patients.

The Mediating Roles of Lung Function Traits and Inflammatory Factors on the Associations between Measures of Obesity and Risk of Lower Respiratory Tract Infections: A Mendelian Randomization Study.

BACKGROUND: Identifying mediators between obesity-related traits and lower respiratory tract infections (LRTIs) would inform preventive and therapeutic strategies to reduce the burden of LRITs. We aimed to recognize whether lung function and inflammatory factors mediate their associations. METHODS: We conducted a two-step, two-sample Mendelian randomization (MR) analysis. Two-sample MR was performed on (1) obesity-related traits (i.e., body mass index [BMI], waist circumference [WC], and waist-to-hip ratio [WHR]) and LRTIs (i.e., acute bronchitis, acute bronchiolitis, bronchiectasis, influenza, and pneumonia), (2) obesity-related traits and potential mediators, and (3) potential mediators and LRTIs. Next, two-step MR was applied to infer whether the mediation effects exist. RESULTS: We found that C-reactive protein (CRP), interleukin-6 (IL-6), and forced expiratory volume in the first second (FEV1) mediated 32.59% (95% CI: 17.90%, 47.27%), 7.96% (95% CI: 1.79%, 14.14%), and 4.04% (95% CI: 0.34%, 7.74%) of the effect of BMI on pneumonia, and they mediated 26.90% (95% CI: 13.98%, 39.83%), 10.23% (95% CI: 2.72%, 17.73%), and 4.67% (95% CI: 0.25%, 9.09%) of the effect of WC on pneumonia, respectively. Additionally, CRP, forced vital capacity (FVC), and FEV1 mediated 18.66% (95% CI: 8.70%, 28.62%), 8.72% (95% CI: 1.86%, 15.58%), and 8.41% (95% CI: 2.77%, 14.06%) of the effect of BMI on acute bronchitis, and they mediated 19.96% (95% CI: 7.44%, 32.48%), 12.19% (95% CI: 2.00%, 22.39%), and 12.61% (95% CI: 2.94%, 22.29%) of the effect of WC on acute bronchitis, respectively. CONCLUSIONS: Health interventions linked to reducing inflammation and maintaining normal lung function could help mitigate the risk of obesity-related LRTIs.

Fat Mass- and Obesity-Associated Protein (FTO) Promotes the Proliferation of Goat Skeletal Muscle Satellite Cells by Stabilizing DAG1 mRNA in an IGF2BP1-Related m6A Manner.

Skeletal muscle development is spotlighted in mammals since it closely relates to animal health and economic benefits to the breeding industry. Researchers have successfully unveiled many regulatory factors and mechanisms involving myogenesis. However, the effect of N6-methyladenosine (m6A) modification, especially demethylase and its regulated genes, on muscle development remains to be further explored. Here, we found that the typical demethylase FTO (fat mass- and obesity-associated protein) was highly enriched in goats' longissimus dorsi (LD) muscles. In addition, the level of m6A modification on transcripts was negatively regulated by FTO during the proliferation of goat skeletal muscle satellite cells (MuSCs). Moreover, a deficiency of FTO in MuSCs significantly retarded their proliferation and promoted the expression of dystrophin-associated protein 1 (DAG1). m6A modifications of DAG1 mRNA were efficiently altered by FTO. Intriguingly, the results of DAG1 levels and its m6A enrichment from FB23-2 (FTO demethylase inhibitor)-treated cells were consistent with those of the FTO knockdown, indicating that the regulation of FTO on DAG1 depended on m6A modification. Further experiments showed that interfering FTO improved m6A modification at site DAG1-122, recognized by Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) and consequently stabilized DAG1 transcripts. Our study suggests that FTO promotes the proliferation of MuSCs by regulating the expression of DAG1 through m6A modification. This will extend our knowledge of the m6A-related mechanism of skeletal muscle development in animals.

The role of trimethylation on histone H3 lysine 27 (H3K27me3) in temozolomide resistance of glioma.

Temozolomide (TMZ) is the first-line chemotherapeutic agent for malignant glioma, but its resistance limited the benefits of the treated patients. In this study, the role and significance of trimethylation of histone H3 lysine 27 (H3K27me3) in TMZ resistance were investigated. Data from twenty advanced glioma patients were collected, and their pathological samples were analyzed for H3K27me3 levels. TMZ sensitivity was compared between glioma cells U87 and TMZ-resistant cells U87TR, with H3K27me3 levels determined in both cells. The effects of H3K27me3 demethylases inhibitor GSK-J4, combined with TMZ, were assessed on the proliferation and migration of U87TR cells. The results indicated that a high level of H3K27me3 predicts longer disease free survival (DFS) and overall survival (OS) in glioma patients receiving TMZ treatment. The H3K27me3 level was lower in U87TR cells compared to U87 cells. GSK-J4 increased the H3K27me3 level in U87TR cells and decreased their resistance to TMZ. In summary, this study identified a novel marker of TMZ resistance in glioma and provided a new strategy to address this challenge. These findings are significant for improving the clinical treatment of glioma in the future.

Genetic variation and population structure of Taenia multiceps (Coenurus cerebralis) based on mitochondrial cox1 gene: A comprehensive global analysis.

Taenia multiceps is a neglected parasite having veterinary and public health importance. The predilection sites of the parasite larva (Coenurus cerebralis) are brain (cerebral coenurosis) and subcutaneous (non-cerebral coenurosis). There is a dearth of data regarding molecular characterization of T. multiceps and even fewer population structure-based studies on T. multiceps. The current study was conducted to provide epidemiological information regarding the global population structure of the parasite. The NCBI GenBank database was accessed to download the sequences of cox1 gene, which were further subjected to PopArt software to construct median-joining networks. The DnaSp software was used to compute neutrality and diversity indices. Host and region-wise indices of neutrality and diversity were also computed. There were 166 gene sequences found in the NCBI database. Followed by removal of short gene sequences, 143 were considered to perform bioinformatic analyses. A total of 30 haplotypes with 46 mutations and 23 parsimony informative sites were found. High diversity (Hd = 0.889, π = 0.01186) and negative but statistically insignificant neutrality indices (Tajima's D = -1.57659, Fu's Fs = -10.552) were found. Region-wise results revealed highest haplotype diversities in isolates from KSA (Hd = 1.00) followed by Greece and Italy (Hd = 0.962), and China (Hd = 0.931). Host-wise data analysis showed an overall negative Tajima's D value and there exists highest haplotype diversity in cattle (Hd = 1.00) followed by dogs (Hd = 0.833), sheep (Hd = 0.795) and goats (Hd = 0.788). The findings of the study indicate that the population diversity of T. multiceps will increase worldwide as shown by high diversity and negative neutrality indices. The findings of the study significantly add-in to the existing bank of knowledge about population structure of T. multiceps. We recommend conducting more studies employing different genetic markers to better comprehend the epidemiology of the parasite.

Angioplasty and/or stenting following successful mechanical thrombectomy for intracranial atherosclerosis-related emergent large vessel occlusive stroke (ASSET): protocol of a multicentre randomised trial.

RATIONALE: The management of residual stenosis after mechanical thrombectomy in patients with intracranial atherosclerotic stenosis-related emerge large vessel occlusive (ICAS-LVO) stroke is still unclear question in clinical practice. AIM: To demonstrate the design of a clinical trial on emergency balloon angioplasty and/or stenting (BAS) combined with standard medical treatment (SMT) for residual stenosis of ICAS-LVO stroke patients with successful recanalisation. DESIGN: ASSET is a multicentre, prospective, randomised, open-label, blinded end-point, controlled clinical trial designed (PROBE) by investigators. This trial evaluates the effectiveness and the safety of emergency BAS in combination with SMT compared with SMT alone in ICAS-LVO stroke patients with successful recanalisation (defined as expanded treatment in cerebral ischaemia grade of 2b50-3 and maintained for more than 20 min) and residual stenosis (defined as ≥50%) up to 24 hours after the onset of symptoms or the last known well. OUTCOME: The primary outcome assessed at 90 (±7) days after randomisation is the incidence of ischaemic stroke in the responsible vessel. Symptomatic intracranial haemorrhage within 24 (±3) hours is the primary safety outcome. DISCUSSION: The ASSET trial is designed to provide strong evidence on the effectiveness and safety of emergency BAS to treat residual stenosis after successful recanalisation in patients with ICAS-LVO stroke. TRIAL REGISTRATION NUMBER: ChiCTR2300079069.

Diet Impacts on Gene Expression in Healthy Colon Tissue: Insights from the BarcUVa-Seq Study.

(1) Introduction: The global rise of gastrointestinal diseases, including colorectal cancer and inflammatory bowel diseases, highlights the need to understand their causes. Diet is a common risk factor and a crucial regulator of gene expression, with alterations observed in both conditions. This study aims to elucidate the specific biological mechanisms through which diet influences the risk of bowel diseases. (2) Methods: We analyzed data from 436 participants from the BarcUVa-Seq population-based cross-sectional study utilizing gene expression profiles (RNA-Seq) from frozen colonic mucosal biopsies and dietary information from a semi-quantitative food frequency questionnaire. Dietary variables were evaluated based on two dietary patterns and as individual variables. Differential expression gene (DEG) analysis was performed for each dietary factor using edgeR. Protein-protein interaction (PPI) analysis was conducted with STRINGdb v11 for food groups with more than 10 statistically significant DEGs, followed by Reactome-based enrichment analysis for the resulting networks. (3) Results: Our findings reveal that food intake, specifically the consumption of blue fish, alcohol, and potatoes, significantly influences gene expression in the colon of individuals without tumor pathology, particularly in pathways related to DNA repair, immune system function, and protein glycosylation. (4) Discussion: These results demonstrate how these dietary components may influence human metabolic processes and affect the risk of bowel diseases.

Investigating the modulatory effects of lactoferrin on depressed rats through 16S rDNA gene sequencing and LC-MS metabolomics analysis.

Lactoferrin is a natural multifunctional glycoprotein with potential antidepressant-like effects. However, the mechanism of its antidepressant effect has not been explored from the perspective of gut flora metabolism. Therefore, we employed both 16S rDNA gene sequencing and LC-MS metabolomics analysis to investigate the regulatory effects and mechanisms of lactoferrin in a rat model of depression. After one week of acclimatization, twenty-four 7-week-old male Sprague-Dawley rats were randomly and equally assigned into three groups: the control group, the model group, and the lactoferrin intervention group. The control group rats were housed under standard conditions, while the rats in the model and lactoferrin intervention groups were individually housed and exposed to chronic unpredictable mild stress for 44 days simultaneously. The lactoferrin intervention group was provided with water containing 2% lactoferrin (2 g/100 ml). Behavioural tests were conducted at week 7. Upon completion of the behavioral tests, the rats were anesthetized with isoflurane, humanely euthanized using a rat guillotine, and tissue samples were collected for further experiments. The results indicated that lactoferrin intervention led to an increase in sucrose solution consumption, horizontal movement distance, number of cross platforms, and residence time in the target quadrant. Additionally, it resulted in an increase in jejunal tight junction protein ZO-1 expression and a suppression of serum expression of inflammatory factors, Lipopolysaccharide and Diamine oxidase. In summary, lactoferrin can regulate the metabolic disorder of intestinal flora, reduce intestinal permeability, and further regulate the metabolic balance of hippocampal tissues through the microbiota-gut-brain axis. This process ultimately alleviates the depression-like behavior in rats.