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Key points Noncontrast computed tomography (NCCT) is valuable for predicting hemorrhagic transformation (HT) after intravenous thrombolysis (IVT) treatment. Machine learning is vital for predicting HT. NCCT radiomics integrated with clinical factors could facilitate predicting HT.

To date, there has been limited research on the interactive effects of yeast and lactic acid bacteria (LAB) on the sensory qualities of navel orange wine. In this study, using Jintang navel orange juice as the raw material, multi-microbial fermentation was conducted with Saccharomyces cerevisiae SC-125 and Angel yeast SY, as well as Lactiplantibacillus plantarum BC114. Single yeast and co-fermentation with Lactiplantibacillus plantarum were used as the control groups. The research aimed to investigate the physicochemical parameters of navel orange wine during fermentation. Additionally, headspace solid-phase microextraction gas chromatography–mass spectrometry (HP-SPME-GC-MS) was employed to determine and analyze the types and levels of flavor compounds in the navel orange wines produced through the different fermentation methods. The co-fermentation using the three strains significantly enhanced both the quantity and variety of volatile compounds in the navel orange wine, concomitant with heightened total phenol and flavonoid levels. Furthermore, a notable improvement was observed in the free radical scavenging activity. A sensory evaluation was carried out to analyze the differences among the various navel orange wines, shedding light on the impact of different wine yeasts and co-fermentation with LAB on the quality of navel orange wines.

Luteolin (LUT) is a fat-soluble flavonoid known for its strong antioxidant and anti-inflammatory properties. Nonetheless, its use in the food industry has been limited due to its low water solubility and bioavailability. In this study, hyaluronic acid, histidine, and luteolin were self-assembled to construct tubular network hydrogels (HHL) to improve the gastrointestinal stability, bioavailability, and stimulation response of LUT. As anticipated, the HHL hydrogel’s mechanical strength and adhesion allow it to withstand the challenging gastrointestinal environment and effectively extend the duration of drug presence in the body. In vivo anti-inflammatory experiments showed that HHL hydrogel could successfully alleviate colitis induced by dextran sulfate sodium (DSS) in mice by reducing intestinal inflammation and restoring the integrity of the intestinal barrier. Moreover, HHL hydrogel also regulated the intestinal microorganisms of mice and promoted the production of short-chain fatty acids. The HHL hydrogel group demonstrated a notably superior treatment effect compared to the LUT group alone. The hydrogel delivery system is a novel method to improve the absorption of LUT, increasing its bioavailability and enhancing its pharmaceutical effects.

Abstract Immune checkpoint blockade (ICB) therapy targeting PD-1/PD-L1 has shown durable clinical benefits in lung cancer. However, many patients respond poorly to ICB treatment, underscoring an incomplete understanding of PD-L1 regulation and therapy resistance. Here, we find that MTSS1 is downregulated in lung adenocarcinoma, leading to PD-L1 upregulation, impairment of CD8+ lymphocyte function, and enhanced tumor progression. MTSS1 downregulation correlates with improved ICB efficacy in patients. Mechanistically, MTSS1 interacts with the E3 ligase AIP4 for PD-L1 monoubiquitination at Lysine 263, leading to PD-L1 endocytic sorting and lysosomal degradation. In addition, EGFR-KRAS signaling in lung adenocarcinoma suppresses MTSS1 and upregulates PD-L1. More importantly, combining AIP4-targeting via the clinical antidepressant drug clomipramine and ICB treatment improves therapy response and effectively suppresses the growth of ICB-resistant tumors in immunocompetent mice and humanized mice. Overall, our study discovers an MTSS1-AIP4 axis for PD-L1 monoubiquitination and reveals a potential combinatory therapy with antidepressants and ICB.

IntroductionPrimary central nervous system lymphoma (PCNSL) is infrequent and represents 3. 1% of primary brain tumors. And the lesions that are restricted to the ventricular system, particularly the third ventricle, are even rarer. There are few pieces of literature or case reports to date. We report a case of PCNSL with partial hypointense on diffusion-weighted imaging (DWI) located in the lateral and third ventricles. Then we reviewed almost all case reports of ventricular PCNSLs in the last 20 years, discuss the imaging presentation, other ventricular tumors with similar imaging findings, and primary treatment measures.Case presentationA 78-year-old man presented with memory loss and poor responsiveness for one week without obvious precipitating factors. Magnetic resonance imaging (MRI) showed lesions in the third ventricle and left lateral ventricles, which were slightly hypointense on T1-weighted imaging (T1WI), and isointense to slightly hypointense on T2-weighted imaging (T2WI). On DWI, the left lateral ventricular lesion was hyperintense, while the third ventricular lesion was hypointense. After the surgical procedure, the pathology and immunohistochemistry revealed diffuse large B-cell lymphoma (DLBCL).ConclusionsVentricular PCNSL is quite rare, and may be confused with other tumors in the same position. However, PCNSL differs from other central nervous system tumors in that it is primarily treated with chemotherapy and/or radiation therapy. So, it is important to recognize PCNSL and differentiate it from other tumors, considering its implications for management planning.

Cisplatin (CDDP) has been widely used in cancer therapy, but it has been linked to side effects such as nephrotoxicity. Crocin is a carotenoid found in crocus and gardenia flowers that has been shown to have anti-oxidant properties, inhibit tumor growth, and provide neuroprotection. The purpose of this study was to investigate the protective effect of crocin against CDDP-induced nephrotoxicity in a mouse model. Kunming mice were administered orally with crocin for 7 days at the dose of 6.25 mg/kg and 12.5 mg/kg per body weight daily and were injected with CDDP via intraperitoneal route at the dose of 10 mg/kg per body weight. Using commercial kits, the oxidative stress markers glutathione, malondialdehyde, catalase, glutathione peroxidase, and superoxide dismutase were measured in the kidneys of mice. Immunohistochemistry was used to assess the levels of p53, cleaved caspase-3, and phospho-p38 mitogen-activated protein kinase in the kidneys. Crocin significantly reduced CDDP-induced changes in serum creatinine and blood urea nitrogen levels, according to the findings. Crocin reduced malondialdehyde levels and increased glutathione, glutathione peroxidase, catalase, and superoxide dismutase levels in CDDP-induced lipid peroxidation. Crocin also significantly inhibited p38 mitogen-activated protein kinase activation, p53 expression, and caspase-3 cleavage. In conclusion, crocin protects against CDDP-induced oxidative stress and nephrotoxicity by attenuating the activation of p38 mitogen-activated protein kinase and caspase-3 cleavage.

Abstract Defects in the DNA damage response (DDR) can lead to genome instability, producing mutations or aberrations that promote the development and progression of cancer. But it also confers such cells vulnerable to cell death when they inhibit DNA damage repair. Poly (ADP-ribose) polymerase (PARP) plays a central role in many cellular processes, including DNA repair, replication, and transcription. PARP induces the occurrence of poly (ADP-ribosylation) (PARylation) when DNA single strand breaks (SSB) occur. PARP and various proteins can interact directly or indirectly through PARylation to regulate DNA repair. Inhibitors that directly target PARP have been found to block the SSB repair pathway, triggering homologous recombination deficiency (HRD) cancers to form synthetic lethal concepts that represent an anticancer strategy. It has therefore been investigated in many cancer types for more effective anti-cancer strategies, including gastric cancer (GC). This review describes the antitumor mechanisms of PARP inhibitors (PARPis), and the preclinical and clinical progress of PARPis as monotherapy and combination therapy in GC.

The polyphenol-rich lentil hulls are the by-product of lentils hulling process. In this manuscript, in vitro digestion, Caco-2 cell monolayer and Caco-2/RAW264.7 cell co-culture model were established to explore their anti-inflammatory mechanism, absorption of digestive products (RLD), and impact on the intestinal barrier. Results shown that high dose RLE and GLE could significantly inhibit the secretion of NO (30.23% and 31.08%, respectively), IL-6 (81.48% and 56.82%, respectively) and IL-1β (88.05% and 91.67%, respectively), and down-regulate the protein and mRNA expression of iNOS (56.46% and 45.69%, respectively) and COX-2 (76.53% and 46.65%, respectively), and inhibit the activation of MAPK and NF-κB signaling pathways. Polyphenols can be released from lentil hulls and protocatechuic acid glycoside derivative has the highest content (2205.09 ± 7.02 μg/g DW). Digestive products can be absorbed by intestine to maintain intestinal barrier and play anti-inflammatory effect. Above all, lentil hulls may be a potentially valuable functional dietary resource.

PurposesThe purpose of this study was to explore the diagnostic performance of Cho peak area (Cho Are), Cho peak amplitude (Cho Amp), and the combined approach (Cho Are_Amp) in detecting rabbit VX2 liver cancer at the early stage via hydrogen-1 proton magnetic resonance spectroscopy (1H-MRS), as well as the correlations between Cho Are, Cho Amp, and tumor parameters like diameter and volume.MethodsConventional magnetic resonance imaging (MRI) and MRS were performed to scan the VX2 liver cancer in rabbit. The tumor diameter was measured on T2-weighted imaging (T2WI), and the tumor volume was accordingly calculated. Cho Are and Cho Amp were obtained from MRS. The diagnostic performance of Cho Are, Cho Amp, and Cho Are_Amp was assessed by a receiver operating characteristic (ROC) curve and area under ROC curve (AUC), whereas specificity and sensitivity were calculated by the maximum Youden’s index. Spearman’s correlation analysis was performed to evaluate the relevance between tumor parameters (diameter, volume) and radiological indexes (Cho Are, Cho Amp).ResultsROC curve analysis showed that Cho Amp, Cho Are, and Cho Are_Amp were effective in diagnosing VX2 liver cancer. The AUC of Cho Amp was 0.883, and the specificity and sensitivity were 0.944 and 0.722, respectively (p < 0.001). The AUC of Cho Are was 0.807, and the specificity and sensitivity were 0.778 and 0.833, respectively (p < 0.05). The AUC of Cho Are_Amp was 0.892, and the specificity and sensitivity were 0.833 and 0.833, respectively (p < 0.001). Cho Are and Cho Amp exhibited a high positive correlation with tumor diameter and tumor volume, among which Cho Amp demonstrated better correlations to tumor diameter and tumor volume (r = 0.956 and 0.946) than that of Cho Are (r = 0.787 and 0.794). A high positive correlation was detected between Cho Are and Cho Amp (r = 0.787), as well as tumor diameter and tumor volume (r = 0.965).ConclusionCho Are_Amp can be used as an effective tool in diagnosing early-stage VX2 liver cancer with satisfied diagnostic accuracy. Cho Are and Cho Amp were positively correlated with tumor volume and tumor diameter. The results of this study provide further evidence that Cho Amp and Cho Are_Amp of MRS could aid in the early diagnosis of liver cancer.

Abstract Background Splicing factor SRSF3 is an oncogene and overexpressed in various kinds of cancers, however, the function and mechanism involved in colorectal cancer (CRC) remained unclear. The aim of this study was to explore the relationship between SRSF3 and carcinogenesis and progression of CRC. Methods The expression of SRSF3 in CRC tissues was detected by immunohistochemistry. The proliferation and invasion rate was analyzed by CCK-8 assay, colony formation assay, transwell invasion assay and xenograft experiment. The expression of selected genes was detected by western blot or real time PCR. Results SRSF3 is overexpressed in CRC tissues and its high expression was associated with CRC differentiation, lymph node invasion and AJCC stage. Upregulation of SRSF3 was also associated with shorter overall survival. Knockdown of SRSF3 in CRC cells activated ArhGAP30/Ace-p53 and decreased cell proliferation, migration and survival; while ectopic expression of SRSF3 attenuated ArhGAP30/Ace-p53 and increases cell proliferation, migration and survival. Targeting SRSF3 in xenograft tumors suppressed tumor progression in vivo. Conclusions Taken together, our data identify SRSF3 as a regulator for ArhGAP30/Ace-p53 in CRC, and highlight potential prognostic and therapeutic significance of SRSF3 in CRC.

Abstract Background Our study aims to develop and validate diagnostic models of the common parotid tumors based on whole-volume CT textural image biomarkers (IBMs) in combination with clinical parameters at a single institution. Methods The study cohort was composed of 51 pleomorphic adenoma (PA) patients and 42 Warthin tumor (WT) patients. Clinical parameters and conventional image features were scored retrospectively and textural IBMs were extracted from CT images of arterial phase. Independent-samples t test or Chi-square test was used for evaluating the significance of the difference among clinical parameters, conventional CT image features, and textural IBMs. The diagnostic performance of univariate model and multivariate model was evaluated via receiver operating characteristic (ROC) curve and area under ROC curve (AUC). Results Significant differences were found in clinical parameters (age, gender, disease duration, smoking), conventional image features (site, maximum diameter, time-density curve, peripheral vessels sign) and textural IBMs (mean, uniformity, energy, entropy) between PA group and WT group (P

Despite recent improvements in treatment modalities, pancreatic cancer remains a highly lethal tumor with mortality rate increasing every year. Poly (ADP-ribose) polymerase (PARP) inhibitors are now used in pancreatic cancer as a breakthrough in targeted therapy. This study focused on whether PARP inhibitors (PARPis) can affect programmed death ligand-1 (PD-L1) expression in pancreatic cancer and whether immune checkpoint inhibitors of PD-L1/programmed death 1 (PD-1) can enhance the anti-tumor effects of PARPis. Here we found that PARPi, pamiparib, up-regulated PD-L1 expression on the surface of pancreatic cancer cells in vitro and in vivo. Mechanistically, pamiparib induced PD-L1 expression via JAK2/STAT3 pathway, at least partially, in pancreatic cancer. Importantly, pamiparib attenuated tumor growth; while co-administration of pamiparib with PD-L1 blockers significantly improved the therapeutic efficacy in vivo compared with monotherapy. Combination therapy resulted in an altered tumor immune microenvironment with a significant increase in windiness of CD8+ T cells, suggesting a potential role of CD8+ T cells in the combination therapy. Together, this study provides evidence for the clinical application of PARPis with anti-PD-L1/PD-1 drugs in the treatment of pancreatic cancer.

The interaction between lentil protein isolate (LPI) and cyanidin-3-O-glucoside (C3G) was investigated via with UV–vis spectroscopy, circular dichroism, and fluorescence spectroscopy and the stability of anthocyanin was also evaluated. After LPI mixed with C3G, the turbidity and foaming capacity increased and the particle size and surface charge did not change significantly, while the surface hydrophobicity decreased significantly (p < 0.05). The fluorescence results indicated that C3G quenched the intrinsic of LPI by static quenching and LPI bound with C3G via hydrophobic effects with Ka of 3.24 × 106 M−1 at 298 K. The addition of LPI significantly (p < 0.05) slightly decreased the thermal and oxidation degradation of C3G by up to 90.23% and 54.20%, respectively, while their antioxidant activity was inhibited upon mixing. These alterations of physicochemical properties might be attributed to their structural changes during the interaction. The obtained results would be of help in stabilizing bioactive compounds and the development of functional foods.

Background: Although ribosomal protein S6 kinases, 90 kDa, polypeptide 3 (RSK2, RPS6KA3) has been reported to play an important role in cancer cell proliferation, invasion, and migration, including breast cancer, its clinical implication in primary breast cancer patients is not well understood, and there were not many studies to explore the relationship between RSK2 and breast cancer on a clinical level.Methods: A systematic series matrix file search uploaded from January 1, 2008 to November 31, 2017 was undertaken using ArrayExpress and Gene Expression Omnibus (GEO) databases. Search filters were breast cancer, RNA assay, and array assay. Files eligible for inclusion met the following criteria: a) sample capacity is over 100, b) tumor sample comes from unselected patient’s primary breast tumor tissue, and c) expression of RSK2 and any clinical parameters of patients were available from the files. We use median as the cutoff value to assess the association between the expression of RSK2 and the clinical indexes of breast cancer patients.Finding: The meta-analysis identified 13 series matrix files from GEO database involving 3,122 samples that come from patients’ primary breast cancer tissue or normal tissue. The expression of RSK2 in tumor tissues is lower than that in normal tissues [odds ratio (OR), 0.54; 95% credible interval (CI), 0.44–0.67; Cochran’s Q test p = 0.14; I2 = 41.7%]. Patients with a high expression of RSK2 showed more favorable overall survival [hazard ratio (HR), 0.71; 95% CI, 0.49–0.94; Cochran’s Q test p = 0.95; I2 = 0.0%] and less potential of distant metastasis (OR, 0.59; 95% CI, 0.41–0.87; Cochran’s Q test p = 0.88; I2 = 0.0%) and lymph node infiltration (OR, 0.81; 95% CI, 0.65–0.998; Cochran’s Q test p = 0.09; I2 = 42.8%). Besides, the expression of RSK2 in luminal breast cancer is lower than Cochran’s Q test p = 0.06; I2 = 63.5%). RSK2 overexpression corresponded with higher histological grade (OR, 1.329; 95% CI, 1.03–1.721; Cochran’s Q test p = 0.69; I2 = 0.0%). RSK2 expression is also associated with estrogen receptor (ER) and age.Conclusion: The meta-analysis provides evidence that RSK2 is a potential biomarker in breast cancer patients. The expression of RSK2 is distinctive in different intrinsic subtypes of breast cancer, indicating that it may play an important role in specific breast cancer. Further study is needed to uncover the mechanism of RSK2 in breast cancer.Systematic Review Registration: (website), identifier (registration number).

Background: To investigate the diagnostic efficacy of choline (Cho) value of magnetic resonance spectroscopy (MRS) in rabbit with VX2 liver tumor via comparative and quantitative analysis with the choline compounds concentration measured by enzyme linked immunosorbent assay (ELISA). Methods: MRS was performed on normal liver and VX2 tumor. The Cho value of VX2 tumor was compared with that of normal liver. Tissues were harvested for ELISA to detect the concentrations of acetylcholine (ACh), glycophorophosphygholine (GPC) and phosphochorine (PC). The diagnostic performance of Cho value and concentrations of choline compounds were assessed by receiver operating characteristic (ROC) curve and area under ROC curve (AUC). The specificity and sensitivity were discussed by the maximum Youden’s index. Results: The concentration of ACh was obviously higher than that of GPC and PC both in VX2 tumor and normal liver ( P < 0.01). Furthermore, the concentration differences among ACh, GPC and PG were the third power of 10. Both the ACh concentration and Cho value of MRS in VX2 tumor were significantly higher than those in normal liver ( P < 0.01). The AUC of ACh in VX2 tumor was 0.883, when the cutoff value was 7259000, the sensitivity and specificity of the diagnosis of liver cancer were 94.4% and 77.8%, respectively. The AUC of Cho in VX2 tumor was 0.807, when the cutoff value was 28.35, the sensitivity and specificity of the diagnosis of liver cancer were 83.3% and 77.8%, respectively. Conclusion: The change of Cho value in MRS between liver cancer and normal liver was consistent with the changes of concentrations of choline compounds measured by ELISA, especially the change of ACh concentration. The diagnostic efficiency of Cho value and that of choline compounds concentration in liver cancer were extremely similar, with the AUC more than 0.8. We conclude that MRS may be applied as an important, non-invasive biomarker for the diagnosis of liver cancer.

Sodium/glucose cotransporter 1 (SGLT1), an essential active glucose transport protein that helps maintain high intracellular glucose levels, was previously shown to interact with epidermal growth factor receptor (EGFR); the SGLT1–EGFR interaction maintains intracellular glucose levels to promote survival of cancer cells. Here, we explore the role of SGLT1 in triple‐negative breast cancer (TNBC), which is the most aggressive type of breast cancer. We performed TCGA analysis coupled to in vitro experiments in TNBC cell lines as well as in vivo xenografts established in the mammary fat pad of female nude mice. Tissue microarrays of TNBC patients with information of clinical–pathological parameters were also used to investigate the expression and function of SGLT1 in TNBC. We show that high levels of SGLT1 are associated with greater tumour size in TNBC. Knockdown of SGLT1 compromises cell growth in vitro and in vivo. We further demonstrate that SGLT1 depletion results in decreased levels of phospho‐EGFR, and as a result, the activity of downstream signalling pathways (such as AKT and ERK) is inhibited. Hence, targeting SGLT1 itself or the EGFR–SGLT1 interaction may provide novel therapeutics against TNBC.

5-demethylnobiletin (5DN) in aged citrus peel (chenpi) is a unique polymethoxyflavone that has been shown to exhibit superior anti-cancer effects, but its low water-solubility and poor oral bioavailability may limit its application as a potent nutraceutical. In this study, Se-enriched peanut protein nanoparticles-stabilized Pickering emulsions (PPEs) were used to encapsulate 5DN to enhance its bioaccessibility, cellular uptake and transport rate. The preparation of PPEs, and their digestion profiles in gastrointestinal tract, cell uptake and transport were investigated. Results showed that the bioaccessibility of 5DN was significantly higher within PPEs (18.3%) than in bulk oil (9.2%). Besides, PPEs-encapsulated 5DN has a greater apical-to-basolateral (AP-BL) transport rate (26.9 × 10−6 cm s−1) than 5DN (21.7 × 10−6 cm s−1). It was proved PPEs may promote the bioavailability of 5DN, and this type of delivery system may be useful for the application of 5DN and other crystalline nutraceuticals in functional foods and beverages.

We aimed to build a deep learning-based, objective, fast, and accurate collateral circulation assessment model. We included 92 patients who had suffered acute ischemic stroke (AIS) with large vessel occlusion in the anterior circulation in this study, following their admission to our hospital from June 2020 to August 2021. We analyzed their baseline whole-brain four-dimensional computed tomography angiography (4D-CTA)/CT perfusion. The images of the arterial, arteriovenous, venous, and late venous phases were extracted from 4D-CTA according to the perfusion time–density curve. The subtraction images of each phase were created by subtracting the non-contrast CT. Each patient was marked as having good or poor collateral circulation. Based on the ResNet34 classification network, we developed a single-image input and a multi-image input network for binary classification of collateral circulation. The training and test sets included 65 and 27 patients, respectively, and Monte Carlo cross-validation was employed for five iterations. The network performance was evaluated based on its precision, accuracy, recall, F1-score, and AUC. All the five performance indicators of the single-image input model were higher than those of the other model. The single-image input processing network, combining multiphase CTA images, can better classify AIS collateral circulation. This automated collateral assessment tool could help to streamline clinical workflows, and screen patients for reperfusion therapy.

Background: Selecting proper postoperative adjuvant therapy is of great importance for prolonging overall survival (OS) of patients with biliary tract cancer (BTC). OS is commonly affected by high rate of postoperative recurrence and metastasis.Purpose: The present study aimed to identify the optimal adjuvant therapy for BTC patients.Method: A comprehensive search was carried out on Pubmed, Web of science, and Embase databases to acquire articles regarding BTC therapy approaches. Subsequently, the hazard ratio (HR) and its 95% confidence intervals (CIs) were applied to evaluate the efficacy of different adjuvant therapy regimens. The GemTc (GemTc.0.8-2) and R (R.3.6.0) software were employed to perform statistical analyses.Result: Data from 22 articles, including 14,646 patients, were quantitatively analyzed. The results showed that in terms of 5-year OS, gemcitabine (GEM) was considered as the optimal adjuvant therapy for BTC compared with chemoradiotherapy (CRT; HR = 0.59; 95% CI = 0.34-0.97), observation (OB; HR = 0.49; 95% CI = 0.33-0.73), and radiotherapy (RT; HR = 0.40; 95% CI = 0.22-0.71). Additionally, 5-fluorouracil (5-FU) exhibited improved efficacy compared with RT (HR = 0.52; 95% CI = 0.29-0.91) and OB (HR = 0.63; 95% CI = 0.43-0.92). When the efficacy of 5-FU was compared with that of GEM, the results showed that 5-FU (HR = 1.29) was more effective than GEM. Furthermore, CRT and RT prolonged positive resection margin (R+)-OS (HR = 0.69; 95% CI = 0.49-1.00) and positive lymph node-(N+)-OS (HR = 0.22; 95% CI = 0.074-0.66) in BTC patients. In terms of median recurrence-free survival (RFS) and 1-year OS, the differences were not statistically significant among different therapeutic interventions.Conclusion: The present study suggested that GEM could be used as a first-line adjuvant therapy for resected BTC patients. Additionally, CRT could be the optimal treatment approach for R+ and N+ patients.

In the present study, three selenium-enriched brown rice protein hydrolysates were prepared by trypsin, their anti-inflammatory mechanism in vitro were investigated. Results obtained from LPS-induced RAW264.7 cell model showed that the 1.0–3.5 kDa peptide fractions exhibited the most effective anti-inflammatory property through inhibiting the production of nitric oxide (NO), prostaglandin E2 (PGE2) and pro-inflammation cytokines including interleukin-6 (IL-6), interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α). The mRNA and protein expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) were also suppressed by 1.0–3.5 kDa peptide fractions. Additionally, the phosphorylation of nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs) signal proteins were blocked after 1.0–3.5 kDa peptide fraction treatments. Above all, the observed anti-inflammatory effects of selenium-enriched brown rice protein hydrolysates were closely related to their Se content. These results illustrated that the 1.0–3.5 kDa peptide fractions could be a novel functional food ingredient for inflammation-related diseases treatment.

The effect of four different extraction methods on physicochemical characteristics and functionalities of chloro-phycocyanin (CP) was investigated. Swelling (S-CP), freezing and thawing (4FT-CP), ultrasonication with freezing and thawing (4FT+U-CP), and the high-pressure cell disruption (HPCD-CP) process affected CP differently, thus resulting in different levels of solubility, DPPH scavenging activity, ABTS scavenging activity, and reducing power. Among the four CPs, HPCD-CP had the highest CP content (15.3%), purity (1.66 ± 0.16), and ∆E value but the lowest ∆b value. The ζ potential of HPCD-CP (−38.8 mV) was the highest, but the average particle size of 4FT+U-CP (719.1 nm) was the highest. UV-Vis absorption spectra and fluorescence spectra illustrated that high-pressure cell disruption-assisted extraction had more profound impacts on the microenvironment of tetrapyrrole chromophores, the environment of aromatic amino acids, and the phycocyanobilin of CP. Furthermore, HPCD-CP and 4FT-CP showed higher solubility and antioxidant activities than S-CP, especially 4FT+U-CP. The results obtained in this study demonstrate that HPCD technology could obtain a food-grade C-phycocyanin product with higher CP concentration, purity, solubility, and antioxidant activity.

Background: The effect of metformin on gut microbiota has been reported, but whether metformin can suppress colorectal cancer (CRC) by affecting gut microbiota composition and rescue F. nucleatum-induced tumourigenicity remains unclear. Methods: To identify microbiota associated with both CRC occurrence and metformin treatment, first, we reanalyzed the gut microbiome of our previous data on two human cohorts of normal and CRC individuals. Subsequently, we summarized microbiota altered by metformin from published literatures. Several taxa, including Fusobacterium, were associated with both CRC occurrence and metformin treatment. We investigated the effect of metformin on APCMin/+ mice given with or without F. nucleatum. 16S rRNA gene sequencing was performed. Findings: We summarized 131 genera altered by metformin from 18 published literatures. Five genera reported to be changed by metformin, including Bacteroides, Streptococcus, Achromobacter, Alistipes and Fusobacterium, were associated with CRC in both of our human cohorts. Metformin relieved the symptoms caused by F. nucleatum administration in APCMin/+ mice, and showed promise in suppressing intestinal tumour formation and rescuing F. nucleatum-induced tumourigenicity. Administration of F. nucleatum and/or metformin had effect on gut microbiome structure, composition and functions of APCMin/+ mice. Interpretation: This study pioneers in predicting critical CRC-associated taxa contributing to the antitumour effect of metformin, and correlating gut microbiome with the antitumour effect of metformin in experimental animals. We presented a basis for future investigations into metformin's potential effect on suppressing F. nucleatum-induced tumor formation in vivo. Funding: This work was supported by grants from the National Natural Science Foundation of China (31701250).

Background. The coexistence of colorectal polyps with laterally spreading tumors (LSTs) is commonly observed during colonoscopy. However, there are rare studies that assess the malignant risks for LSTs with colorectal polyps, which might largely contribute to further strategies of treatment and follow-up plans in LSTs. Methods. We conducted a retrospective cohort study that enrolled 206 patients with LSTs in the Endoscopy Center and Endoscopy Research Institute, Renji Hospital, Shanghai Jiao Tong University, China. The subjects with LSTs were divided into two groups: the nonpolyp group with 89 patients and the polyp group with 117 patients. Binary logistic regression was used to identify the independent predictors of outcomes of interest. Results. The risk of the polyps’ coexistence phenomenon increased in males compared with females (OR=2.138, p=0.047), especially in those between 50 and 75 years old (OR=7.074, p=0.036). Tumor size (3–4 cm), LSTs with tubulovillous types, and history of polyps statistically increased the risk of the polyp coexistence phenomenon (OR=5.768, p=0.003; OR=36.345, p=0.024; OR=13.245, p

Abstract Background Most Neonatal Intensive Care Units (NICUs) in China have restricted visiting policies for parents. This also implicates that parents are not involved in the care of their infant. Family Integrated Care (FIC), empowering parents in direct care delivery and decisions, is becoming the standard in NICUs in many countries and can improve quality-of-life and health outcomes of preterm infants. The aim of this study was to evaluate the impact of a FIC intervention on the clinical outcomes of preterm infants with Bronchopulmonary Dysplasia (BPD). Methods A pre-post intervention study was conducted at NICUs in two Chinese children’s hospitals. Infants with BPD were included: pre-intervention group (n = 134) from December 2015 to September 2016, post-intervention (FIC) group (n = 115) and their parents from October 2016 to June 2017. NICU nurses were trained between July and September 2016 to deliver the FIC intervention, including parent education and support. Parents had to be present and care for their infant minimal three hours a day. The infants’ outcome measures were length-of-stay, breastfeeding, weight gain, respiratory and oxygen support, and parent hospital expenses. Results Compared with control group (n = 134), the FIC group (n = 115) had significantly increased breastfeeding rates (83% versus 71%, p = 0.030), breastfeeding time (31 days versus 19 days, p

As a processing by-product, green pea hull (GPH) was found to be rich in phenolic components in our previous studies. In this study, UHPLC-LTQ-OrbiTrap-MS (Ultra performance liquid chromatography-linear ion trap orbitrap tandem mass spectrometry) technique was used to quantify polyphenols, and DSS (sodium dextran sulfate)-induced colitis mouse model was established to explore the effect of GPH extracts on colitis. The results showed that quercetin and its derivatives, kaempferol trihexanside and catechin and its derivatives were the main phenolic substances in the extract, reaching 2836.57, 1482.00 and 1339.91 µg quercetin/g GPH extract, respectively; GPH extracts can improved inflammatory status, repaired colonic function, regulated inflammatory factors, and restored oxidative balance in mice. Further, GPH extracts can activate Keap1-Nrf2-ARE signaling pathway, regulate downstream antioxidant protease and gut microbiota by increasing F/B value and promoting the growth of Lactobacillaceae and Lachnospiraceae, and improve the level of SCFAs (short-chain fatty acids) to relieve DSS-induced colitis in mice. Therefore, GPH may be a promising dietary resource for the treatment of ulcerative colitis.

Abstract Background Itraconazole has been proved therapeutically effective against a variety of human cancers. This study assessed the effect of itraconazole on the Hedgehog (Hh) pathway and proliferation of human gastric cancer cells. Methods CCK-8 assay and colony formation assay were used to assess the effects of itraconazole on proliferation of gastric cancer cells. The expression of Hh signaling components in gastric cancer cells treated with itraconazole was evaluated by reverse-transcription polymerase chain reaction, immunoblotting and dual luciferase assay. Tumor xenograft models were used to assess the inhibitory effect of itraconazole on the proliferation of gastric cancer cells in vivo. Results Itraconazole could remarkably inhibit the proliferation of gastric cancer cells. When in combination with 5-FU, itraconazole significantly reduced the proliferation rate of cancer cells. Furthermore, itraconazole could regulate the G1-S transition and induce apoptosis of gastric cancer cells. Hh signaling was abnormally activated in human gastric cancer samples. In vitro, studies showed that the expression of glioma-associated zinc finger transcription factor 1 (Gli1) was decreased at both transcriptional and translational levels after treatment with itraconazole. Dual luciferase assay also indicated that itraconazole could inhibit the transcription of Gli1. In vivo studies demonstrated that monotherapy with itraconazole by oral administration could inhibit the growth of xenografts, and that itraconazole could significantly enhance the antitumor efficacy of the chemotherapeutic agent 5-FU. Conclusions Hh signaling is activated in gastric tumor and itraconazole can inhibit the growth of gastric cancer cells by inhibiting Gli1 expression.

This study aimed to evaluate the beneficial effects of novel hydrolysates produced by limited enzymatic broken rice (HEBR) on the growth performance, intestinal morphology, and gut microbiota of weaned piglets. During the enzymatic hydrolysis, the primary component of HEBR was maltooligosaccharides (significantly increased to 85.15% at 105 min). Compared to that of the Control group, the average daily gain and feed efficiency, and the villus height in the jejunum and ileum of weaned piglets, was significantly higher in the HEBR group. An increase in Bifidobacterium and Streptococcus was observed in the duodenum and ileum, while a decrease in Escherichia-Shigella was detected in the duodenum, jejunum, ileum and cecum of the weaned piglets with consumption of HEBR. Collectively, supplemental HEBR in the diet helps regulate the gut microbiota and improve the growth performance and intestinal morphology of weaned piglets. Hence, HEBR has the potential to be used as a functional food.

A 54-year-old woman with hairy cell leukemia developed severe polymorphic erythema and blisters on the trunk and limbs after injection of interferon (IFN) α-2b. Skin biopsy revealed lymphocytic exocytosis and perivascular lymphocytic infiltrate in the dermis, and the lesions improved after methylprednisolone pulse therapy. Although injection-site reactions have been observed after injection of IFNα-2b, this is the first report of a widespread cutaneous reaction to IFNα-2b.

A Correction to this paper has been published: https://doi.org/10.1038/s41419-021-03530-0

Currently, no therapeutic options exist for castration-resistant prostate cancer (CRPC) patients who have developed resistance to the second generation anti-androgen receptor (AR) axis therapy. Here we report that co-deletion of Pten and p53 in murine prostate epithelium, often observed in human CRPC, leads to AR-independent CRPC and thus confers de novo resistance to second generation androgen deprivation therapy (ADT) in multiple independent yet complementary preclinical mouse models. In contrast, mechanism-driven co-targeting hexokinase 2 (HK2)-mediated Warburg effect with 2-deoxyglucose (2-DG) and ULK1-dependent autophagy with chloroquine (CQ) selectively kills cancer cells through intrinsic apoptosis to cause tumor regression in xenograft, leads to a near-complete tumor suppression and remarkably extends survival in Pten−/p53-deficiency-driven CRPC mouse model. Mechanistically, 2-DG causes AMPK phosphorylation, which in turn inhibits mTORC1-S6K1 translation signaling to preferentially block anti-apoptotic protein MCL-l synthesis to prime mitochondria-dependent apoptosis while simultaneously activates ULK1-driven autophagy for cell survival to counteract the apoptotic action of anti-Warburg effect. Accordingly, inhibition of autophagy with CQ sensitizes cancer cells to apoptosis upon 2-DG challenge. Given that 2-DG is recommended for phase II clinical trials for prostate cancer and CQ has been clinically used as an anti-malaria drug for many decades, the preclinical results from our proof-of-principle studies in vivo are imminently translatable to clinical trials to evaluate the therapeutic efficacy by the combination modality for a subset of currently incurable CRPC harboring PTEN and TP53 mutations.

Existing data suggest that proton pump inhibitors (PPIs), particularly omeprazole, have significant anti-tumor action in monotherapy and or combination chemotherapy. Hedgehog (Hh) signaling pathway represents a leading candidate as a molecular mediator of Barrett’s esophagus (BE). Studies have indicated reduced miRNAs in BE progression, however, little is known about the latent anti-neoplasm effects of miRNAs in BE cells. Here, we investigated whether omeprazole could inhibit BE progression by regulating Hh pathway and explored the promising Hh-targeted miRNAs in BE cells. We conducted qRT-PCR and immunoblotting assay to evaluate the effects of omeprazole on the expression of Hh signaling components and miR-203a-3p in CP-A and CP-B cells. The promising target genes of miR-203a-3p were predicted by bioinformatics methods, and verified by luciferase assays and qRT-PCR. The effects of omeprazole on BE cell proliferation and cell cycle distribution were determined. The overexpression or silencing of miR-203a-3p was performed to test its anti-proliferative effects. Finally, rescue experiments that miR-203a-3p inhibitor alleviated the effects of omeprazole on decreasing the levels of Gli1 mRNA, protein and luciferase were performed. Mechanistic studies showed that omeprazole could inhibit the expression of Gli1 and the nuclear localization of Gli1. Moreover, we determined that omeprazole could selectively up-regulated the expression of miR-203a-3p, and Gli1 was a bona fide target of miR-203a-3p. miR-203a-3p inhibitor alleviated the suppressing effects of omeprazole on Gli1 luciferase activity, mRNA and protein level. The functional assay suggested that omeprazole could dose-dependently inhibit BE cell growth and induce cell cycle arrest in G0/G1 phase. Additionally, overexpression and silencing of miR-203a-3p in BE cells disrupted cell cycle progress, resulting in suppressing and accelerating cell proliferation, respectively. Taken together, these data provide a novel mechanism of potentially anti-neoplastic effects for omeprazole through modulation of miR-203a-3p expression and thus suppressing Hh/Gli1 signaling in BE cells.

Proton pump inhibitors (PPIs) have been used for treatment of Barrett's esophagus (BE) for many years. However, the connection between PPIs and esophageal adenocarcinoma (EAC) in patients with BE has still been controversial. The current systematic review and meta-analysis was designed to evaluate the association between PPIs and the risk of EAC or high-grade dysplasia (HGD) in patients with BE.A systematic literature search of studies reporting the association between PPIs and the risk of EAC and/or HGD in patients with BE was conducted in PubMed, Embase, Web of Science and the Cochrane Library. Next, literature was screened using previously established criteria and relevant data were extracted from included studies. Finally, the software program Review Manage 5.2 was applied to aggregate data and analyze the results.Nine observational studies, comprising five cohort and four case-control studies (including a total of 5712 patients with BE), were identified. Upon meta-analysis, PPIs were found to have no association with the risk of EAC and/or HGD in patients with BE (unadjusted OR 0.43, 95% CI 0.17-1.08). Analysis for duration response relationship revealed no significant trend toward protection against EAC or HGD with PPIs usage for >2~3 years (one study using 7-year cutoff) when compared to usage for shorter time periods (PPIs usage >2~3 years vs.

Accumulating evidence suggests that codeletion of the tumor suppressor genes Pten and p53 plays a crucial role in the development of castration-resistant prostate cancer in vivo. However, the molecular mechanism underlying Pten-/p53-deficiency-driven prostate tumorigenesis remains incompletely understood. Building upon insights gained from our studies with Pten-/p53-deficient mouse embryonic fibroblasts (MEFs), we report here that hexokinase 2 (HK2) is selectively upregulated by the combined loss of Pten and p53 in prostate cancer cells. Mechanistically, Pten deletion increases HK2 mRNA translation through the activation of the AKT-mTORC1-4EBP1 axis, and p53 loss enhances HK2 mRNA stability through the inhibition of miR143 biogenesis. Genetic studies demonstrate that HK2-mediated aerobic glycolysis, known as the Warburg effect, is required for Pten-/p53-deficiency-driven tumor growth in xenograft mouse models of prostate cancer. Our findings suggest that HK2 might be a therapeutic target for prostate cancer patients carrying Pten and p53 mutations.

Acyl migration (AM) is the main side reaction in the large-scale, regio-specific lipase catalyzed production of structural triglycerides (STs). A detailed understanding of the mechanism of AM was obtained during the process of lipase-catalyzed schemes (LCSs), which play a vital role in improving the quality and total yield of STs. However, currently, the mechanism of AM remains controversial. Herein, the two mechanisms (non-catalyzed (NCM) and lipase-catalyzed (LCM)) of AM have been analyzed in detail by the density functional theory (DFT) at the molecular level. Based on the computational results, we concluded that the energy barrier of the rate-limiting step in the LCM was 18.8 kcal/mol, which is more in agreement with the available experimental value (17.8 kcal/mol), indicating that LCM could significantly accelerate the rate of AM, because it has an energy barrier ~2 times lower than that of the NCM. Interestingly, we also found that the catalytic triad (Asp-His-Ser) of the lipase and water could effectively drop the reaction barrier, which served as the general acid or base, or shuttle of the proton.

The dimensions of microbumps in three-dimensional integration reach microscopic scales and thus necessitate a study of the multiscale microstructures in microbumps. Here, we present simulated mesoscale and atomic-scale microstructures of microbumps using phase field and phase field crystal models. Coupled microstructure, mechanical stress, and electromigration modeling was performed to highlight the microstructural effects on the reliability of microbumps. The results suggest that the size and geometry of microbumps can influence both the mesoscale and atomic-scale microstructural formation during solidification. An external stress imposed on the microbump can cause ordered phase growth along the boundaries of the microbump. Mesoscale microstructures formed in the microbumps from solidification, solid state phase separation, and coarsening processes suggest that the microstructures in smaller microbumps are more heterogeneous. Due to the differences in microstructures, the von Mises stress distributions in microbumps of different sizes and geometries vary. In addition, a combined effect resulting from the connectivity of the phase morphology and the amount of interface present in the mesoscale microstructure can influence the electromigration reliability of microbumps.

Foliar Selenium (Se) fertilizer has been widely used to accumulate Se in rice to a level that meets the adequate intake level. The Se content in brown rice (Oryza sativa L.) was increased in a dose-dependent manner by the foliar application of sodium selenite as a fertilizer at concentrations of 25, 50, 75, and 100 g Se/ha. Selenite was mainly transformed to organic Se, that is, selenomethionine in rice. Beyond the metabolic capacity of Se in rice, inorganic Se also appeared. In addition, four extractable protein fractions in brown rice were analyzed for Se concentration. The Se concentrations in the glutelin and albumin fractions saturated with increasing Se concentration in the fertilizer compared with those in the globulin and prolamin fractions. The structural analyses by fluorescence spectroscopy, Fourier transform infrared spectrometry, and differential scanning calorimetry suggest that the secondary structure and thermostability of glutelin were altered by the Se treatments. These alterations could be due to the replacements of cysteine and methionine to selenocysteine and selenomethionine, respectively. These findings indicate that foliar fertilization of Se was effective in not only transforming inorganic Se to low-molecular-weight selenometabolites such as selenoamino acids, but also incorporating Se into general rice proteins, such as albumin, globulin glutelin, and prolamin, as selenocysteine and selenomethionine in place of cysteine and methionine, respectively.

Abnormalities in the STAT3 pathway are involved in the oncogenesis of several cancers. However, the mechanism by which dysregulated STAT3 signaling contributes to the progression of human colorectal cancer (CRC) has not been elucidated, nor has the role of JAK, the physiological activator of STAT3, been evaluated. To investigate the role of both JAK and STAT3 in CRC progression, we inhibited JAK with AG490 and depleted STAT3 with a SiRNA. Our results demonstrate that STAT3 and both JAK1 and 2 are involved in CRC cell growth, survival, invasion, and migration through regulation of gene expression, such as Bcl-2, p16ink4a, p21waf1/cip1, p27kip1, E-cadherin, VEGF, and MMPs. Importantly, the FAK is not required for STAT3-mediated regulation, but does function downstream of JAK. In addition, our data show that proteasome-mediated proteolysis promotes dephosphorylation of the JAK2, and consequently, negatively regulates STAT3 signaling in CRC. Moreover, immunohistochemical staining reveals that nuclear staining of phospho-STAT3 mostly presents in adenomas and adenocarcinomas, and a positive correlation is found between phospho-JAK2 immunoreactivity and the differentiation of colorectal adenocarcinomas. Therefore, our findings illustrate the biologic significance of JAK1, 2/STAT3 signaling in CRC progression and provide novel evidence that the JAK/STAT3 pathway may be a new potential target for therapy of CRC.

BACKGROUND: Tumor hypoxia plays a fundamental role in resistance to therapy and disease progression. A number of studies have assessed the prognostic role of HIFs expression in head and neck cancer (HNC), but no consistent outcomes are reported. METHODOLOGY: A systematical search was performed to search relevant literatures in PubMed, Web of Science and ISI Web of Knowledge databases. The patients' clinical characteristics and survival outcome were extracted. The correlation between HIFs expression and prognosis was analyzed. PRINCIPAL FINDINGS: A total of 28 studies assessed the association between HIFs and HNC survival, the result showed that overexpressed HIFs was significantly associated with increase of mortality risk (HR = 2.12; 95% CI: 1.52-2.94; I(2) 74%). Subgroup analysis on different HIF isoforms with OS indicated that both HIF-1α and HIF-2α were associated with worse prognosis. The pooled HRs were 1.72(95% CI 1.34-2.20; I(2) 70.7%) and 1.79(95% CI: 1.42-2.27, I(2) 0%). Further subgroup analysis was performed by different geographical locations, disease subtype, stage, types of variate analysis and cut-off value. The results revealed that overexpressed HIF-1α was significantly associated with poor prognosis in Asian patients (HR = 2.34; 95% CI: 1.76-3.1; I(2) 48.9%), but not in European patients (HR = 1.13; 95% CI: 0.77-1.66; I(2) 78.3%). Furthermore, HIF-1α overexpression was significantly associated with worse OS in oral carcinoma (HR = 2.1; 95% CI: 1.11-3.97; I(2) 81.7%), nasopharyngeal carcinoma (HR = 2.07; 95% CI:1.23-3.49; I(2) 22.5%) and oropharynx carcinoma (HR = 1.76; 95% CI:1.05-2.97; I(2) 61%), but not in laryngeal carcinoma (HR = 1.38; 95% CI: 0.87-2.19; I(2) 62.5%). We also found that the prognostic value of HIF-1α overexpression existed only when using staining and percentage as positive definition (HR = 1.82; 95% CI 1.42-2.33; I(2) 9.9%). CONCLUSIONS: This study showed that overexpressed HIFs were significantly associated with increase of mortality risk. Subgroup analysis revealed that overexpressed HIF-1α was significantly associated with worse prognosis of HNC in Asian countries. Additionally, HIF-1α had different prognostic value in different HNC disease subtypes.

Calcium has been proposed as a mediator of the chemoprevention of colorectal cancer (CRC), but the comprehensive mechanism underlying this preventive effect is not yet clear. Hence, we conducted this study to evaluate the possible roles and mechanisms of calcium-mediated prevention of CRC induced by 1,2-dimethylhydrazine (DMH) in mice.For gene expression analysis, 6 non-tumor colorectal tissues of mice from the DMH + Calcium group and 3 samples each from the DMH and control groups were hybridized on a 4×44 K Agilent whole genome oligo microarray, and selected genes were validated by real-time polymerase chain reaction (PCR). Functional analysis of the microarray data was performed using KEGG and Gene Ontology (GO) analyses. Hub genes were identified using Pathway Studio software.The tumor incidence rates in the DMH and DMH + Calcium groups were 90% and 40%, respectively. Microarray gene expression analysis showed that S100a9, Defa20, Mmp10, Mmp7, Ptgs2, and Ang2 were among the most downregulated genes, whereas Per3, Tef, Rnf152, and Prdx6 were significantly upregulated in the DMH + Calcium group compared with the DMH group. Functional analysis showed that the Wnt, cell cycle, and arachidonic acid pathways were significantly downregulated in the DMH + Calcium group, and that the GO terms related to cell differentiation, cell cycle, proliferation, cell death, adhesion, and cell migration were significantly affected. Forkhead box M1 (FoxM1) and nuclear factor kappa-B (NF-κB) were considered as potent hub genes.In the DMH-induced CRC mouse model, comprehensive mechanisms were involved with complex gene expression alterations encompassing many altered pathways and GO terms. However, how calcium regulates these events remains to be studied.

Introduction: Chlorogenic acid (CGA) has been identified to possess salient antiinflammatory, antioxidant, and anticancer attributes. However, its application is limited by its instability and low bioavailability. Liposomes have been considered effective pharmaceutical delivery vehicles due to their ability to continuously release loaded drugs, improve drug stability, and display good biocompatibility. They can be easily modified by other small molecules to acquire additional biological functions. In this study, we developed and characterized folic acid-TPGS-modified chlorogenic acid liposome (FTCLP) and evaluated its antiinflammatory activity. Methods: The successful encapsulation of CGA within FTCLP was confirmed through examination using electron microscopy, fourier-transform infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The in vitro release characteristics of FTCLP were evaluated using the dialysis bag membrane method. Meanwhile, a dextran sulfate sodium (DSS) -induced colitis model was employed to investigate the anti-inflammatory effect of FTCLP and its mechanism. Results: The FTCLP exhibited an encapsulation efficiency (EE) of 84.85 ± 1.20% and a drug loading (DL) of 11.67 ± 0.04%. The particle size of FTCLP was determined to be 150.63 ± 0.71 nm, with a polydispersity index (PDI) of 0.198 ± 0.02 and a zeta potential of 2.61 ± 0.38 mV. The in vitro release profile followed the Higuchi model, indicating sustained-release characteristics. The in vivo study demonstrated that FTCLP treatment was effective in improving the symptoms of DSS-induced inflammatory response, as evidenced by mitigation of weight loss, reduction in the disease activity index (DAI) score, restoration of colon length, and attenuation of colon tissue damage. Furthermore, the levels of pro-inflammatory cytokines, including interferon-gamma (INF-γ), interleukin-1 beta (IL-1β), and interleukin-6 (IL-6), were markedly diminished in both the serum and colon tissue. FTCLP was also observed to suppress the expression of INF-γ, IL-1β, IL-6, tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB) p65, while concomitantly upregulating the expression of Janus kinase (JAK) and signal transducer and activator of transcription 3 (STAT3). Besides, the administration of FTCLP was found to result in an increase in the abundance of Lactobacillaceae and Peptostreptococcaceae, while decreasing the abundance of Bacteroidaceae, Rikenellaceae, and Helicobacteraceae. Conclusion: Following encapsulation of CGA within liposomes, FTCLP revealed favorable stability and sustained release properties, and enhanced the antiinflammatory effects by modulating multiple inflammation-related biomarkers. FTCLP has the potential to be a safe and effective drug for targeted therapy of colitis. [ABSTRACT FROM AUTHOR]